AntiNMDA
19.1K views | +44 today
Follow
 
Scooped by Nesrin Shaheen
onto AntiNMDA
Scoop.it!

Predicting the outcome of a comatose patient at the bedside | Practical Neurology

Predicting the outcome of a comatose patient at the bedside | Practical Neurology | AntiNMDA | Scoop.it
Introduction We, as the neurologists, have all been asked to see ‘unresponsive’ patients immobile in bed, on a ventilator, doing nothing, with no movement, no grimace except for an occasional twitch and, when eyes are opened, a blank stare. What do we say? What can we say? We do not want to ‘write the obituary’ for a patient who might be sitting in a chair the next day. (‘Have you seen Mr. Taylor? You won’t believe it!’) We do not want to tell families not to lose hope (or worse, that ‘time will tell’) when we are pretty convinced that the status will not change for the better. We cannot (and should not) provide escalating intensive care to a patient who, because of a significant injury, is in devastatingly poor shape or even imminently close to brain death. Any neurologist will approach these patients with trepidation because we seldom know enough about their circumstances; their hospital course has been long and complicated, and prior (sometimes critically essential) details are hard to find in the records. Prognostication of coma is difficult; truly it is. Algorithms are inherently artificial, lack the necessary precision and performance and never account for all those confounders (drugs, drugs, drugs) and medical illness, either present or intercurrent. Many new guidelines are derivatives of older ones and the parameters have not changed, only their interpretation. This review is an amalgamation of literature review and opinions, as well as an attempt to establish some procedure to address the questions. The neurologist’s prognostications are not scientific instruments. Neurology is not like that. Definition of coma A traditional, but simple and useful distinction, is to separate states by the degrees of wakefulness and awareness (figure 1). This distinction allows us to separate coma from a persistent vegetative state (and severe forms of minimally conscious state, MCS). Coma denotes being unaware and not awake. Clinicians have gone farther in describing a comatose patient, and this includes descriptions of eye movements (absent fixation or finger tracking), motor responses (absent localisation or reflexive movements) and no verbal output but of no significance in many instances, because comatose patients are intubated to protect the airway. Attempts to categorise coma into several grades of severity have proven futile unless the evaluation takes into account the absence of one or more brainstem reflexes. An important clinical fact is that most patients in coma recover and become more awake. Prolonged disorders of consciousness, such as a vegetative state or MCS, are, therefore, rarely seen after the first year of the injury. It is also a real possibility that patients were misdiagnosed and misclassified after being admitted to neurorehabilitation centres or nursing homes.1 Researchers have subclassified MCSs into those with (MCS+) or without language (MCS–); those with language are more likely to improve further. The classification becomes less articulate since functional MR scan-based categorisation has identified a patient subset fulfilling all vegetative state criteria but in whom functional MR showed a command-following response. Doing or asking something to the patient creates brain activation maps. Another patient subset, higher order cortex motor dissociation, shows a cortical response to the auditory stimuli, again without evident awareness.2 Similar observations have been made with EEG power spectral analysis both early3 and late4 in the clinical course. EEG responses to spoken simple one-task commands were variable among the small group of patients who responded. Responses on EEG spectra and MR cannot (yet) be seen as proof of awareness and may cause considerable disquiet if deciding family members interpret them as such. More importantly, neurologists do not seem to know how to channel these research observations into the practice of prognostication. Figure 1 Definition of coma and vegetative state. Once coma is diagnosed, any clinician will seek an explanation, and in most cases, the explanation can be found through neuroimaging, electrophysiology or cerebrospinal fluid evaluation. It is uncommon to still have a patient with an unexplained coma 24 hours after the admission. When confronted with such an unresolved situation, the neurologist should seek a less common cause, such as an undetected toxin or prolonged, unrecorded hypoglycaemia or anoxia. Emergency departments, worldwide, see coma from opioids, anoxic–ischaemic injury after cardiopulmonary resuscitation, traumatic brain injury, status epilepticus, acute central nervous system (CNS) infections and rapid multiorgan failure. Psychiatric causes for coma do exist, but they are not of long duration. They are quite rare, declare themselves quickly and are not further considered. Extreme forms of catatonia (previously known as lethal catatonia) require a careful assessment and often a search for autoimmune encephalitis. We can safely say that most comas originate from neuronal depression due to intoxication, acute metabolic or endocrine derangement or a lesion in crucially important brain structures. In the case of a structural brain injury, the affected structures are the bilateral cortex or white-matter connections to the cortex, thalamus, dorsal pons and midbrain containing the fibres of the ascending reticular activating system. Acute coma will involve each of these structures. Deepening or emerging coma from a lesser state of impaired consciousness can result from a unilateral lesion displacing other structures from mass effect and causing those structures to become dysfunctional, either from a pressure effect or through ischaemia when the feeding arteries are threatened. Neuroimaging, frequently just a CT scan by itself, often establishes the cause. MRI becomes exceedingly important in the workup of a patient when the cause cannot be established. For example, it may show posterior reversible encephalopathy syndrome not clearly imaged on CT scan and any of the more severe leucoencephalopathies associated with illicit drug use. Patients rarely go into non-convulsive status epilepticus ‘out of the blue’; usually, there are clinical signs pointing to it (blinking, eye deviation and jaw twitching). In any patient in whom the EEG shows epileptiform activity, further monitoring might be necessary. We all think of it, hoping that it is the cause, but we very rarely diagnose non-convulsive status epilepticus clinically or electrographically—despite consulting on a large volume of patients admitted to medical or surgical intensive care units with no prior neurological injury. Other studies have claimed higher percentages (still less than 10%) in comatose patients treated for a critical illness but without a proven effect on outcome after treatment. Transformation of generalised convulsive status epilepticus to non-convulsive status epilepticus is far more common and eminently treatable.5 Before we can prognosticate, we must diagnose the condition. Wrong diagnoses lead to incorrect prognoses (but not always). Much may be said for experience. Indeed, some studies suggest that seniority of staff boosts chances of survival, but careful assessment of all possible variables remains key.6 7 Additionally, before we prognosticate, we must consider all potential (including aggressive) treatments. No neurologist should entertain an outcome prediction if the results of a medical or surgical treatment are not yet known. An additional important, seldom mentioned or acknowledged factor is the early recognition of the cause of coma. Outcome has to be linked to time of intervention and acting quickly. Untreated hydrocephalus, prolonged pressure effect from a mass, untreated large-vessel occlusion and untreated (or inadequately treated) seizures or infection can all impede recovery. There are several situations where timely and aggressive treatment may lead to substantial recoveries. These recoveries may surprise the uninitiated but should not surprise the experienced neurologist (box 1). Box 1 Ten ‘surprising’ coma recoveries Acute meningitis (treated). Acute subdural haematoma (evacuated). Acute hydrocephalus (drained). Intoxications (antidotes). Non-convulsive status epilepticus (antiepileptic medications). Uraemic encephalopathy (dialysis). Posterior reversible encephalopathy syndrome (lowered blood pressure). Myxoedema coma (thyroid supplement). Basilar artery embolus (clot retrieval). Accidental hypothermia (warming). Principles of prognostication in coma Accurate prognostication is based on good judgement, and the key to good judgement is good evaluation of all the information. In some situations, it is coming to terms with it; in others, it is better to deflect a request to make a final decision. The main principles in assessing the patient in prolonged (>24 hours) coma are (1) to examine and identify what counts; (2) to review neuroimaging and know what matters; (3) to evaluate laboratory tests and ancillary tests to see what is missing; (4) to find confounders and consider contributing factors that might have been forgotten; (5) to decide and acknowledge inevitable uncertainties; (6) to factor in the bigger picture (ie, the patient’s previously stated wishes regarding independence and comorbidity); (7) to refrain from predictions if all too confusing; (8) to proceed with a brain-death examination to declare a patient brain dead (the deceased have no prognoses); (9) to speak candidly with family members in a scheduled conference with all medical stakeholders and (10) to proceed with an agreed-on de-escalation plan or withdrawal of support when the best time has been identified. This may help to answer the most commonly asked questions (ie, what is the likelihood that patients will die or remain in an absolutely hopeless condition whatever we do? How far should treatment go?) Prognosis by disease categories It is important to confirm the manner in which the brain has been injured and to identify important and clinical and laboratory data specific to certain disorders. These prime indicators of outcome are critical to an accurate prognosis. Neurologists are often (and undeservedly) mislabelled as harbingers of doom or nihilists, but our goal is to distinguish between the situations that are futile and situations in which the patient has a ‘fighting chance’ (often, when others are ready to give up) and may gain some state of self-reliance. But prognostication for full recovery after a major neurological injury leading to coma continues to elude us. Coma and traumatic brain injury In the elderly, any major traumatic brain injury resulting in coma generally has a poor outcome. Age remains the most important determinant and most indicative variable.8–10 Prognostication in the case of a young adult with a traumatic brain injury is difficult.11 Traumatic brain injury in younger persons (<40 years) remains a ‘roll of the dice’ probability in any multicentre, large-database model.10 While many awaken, survive and improve to the point of walking, talking and taking care of basic needs, their recovery is often accompanied by depression, new addictions, epilepsy and emotional instability. Certain variables, including prolonged severe hypotension and anoxia during injury or during transport to hospital, light-fixed pupils or extensor motor responses, move the needle somewhat but not enough to claim these models as clinical bedside aids. Neuroimaging is seldom definitive, but the presence of primary traumatic brainstem lesions on neuroimaging consistently indicates a poor prognosis12 (figure 2). Similarly, MR-confirmed lesions of the genu of corpus callosum correlate with severe disability. Each of these lesions represents major flexion–extension tearing injuries to the parenchymal structures. Figure 2 Primary brainstem trauma with basal ganglia contusion. Another determinant is sustained, increased intracranial pressure, and we can expect this to lead to a shift of the brain tissue, displacement of the thalamus and midbrain, and a change in pupil size and light responses. Decompressive hemicraniectomy as a treatment for intractable increased intracranial pressure results in a 6-month postoperative mortality rate around 30% but with no measurable effect on the severity of morbidity.13 14 Traumatic brain injury with evacuation of a contusion or epidural or subdural haematoma may lead to protracted recovery. Despite adequate removal of the subdural hematoma, patients may take weeks to improve, and many need close EEG monitoring for seizures.15 In any patient with traumatic brain injury, physicians should watch for the presence of paroxysmal sympathetic hyperactivity. Physicians unfamiliar with this complication may consider these manifestations a mere epiphenomenon of severe brain injury. Paroxysmal sympathetic hyperactivity (‘storming’) after traumatic brain injury is often associated with a worse neurological outcome with longer rehabilitation stays and more cognitive impairment. Paroxysmal sympathetic hyperactivities are rapid and episodic manifestations of excessive sympathetic activity (tachycardia; hypertension with increased pulse pressure, tachypnoea, fever spike and diaphoresis; and increased muscle tone assuming extensor or dystonic postures). An effective treatment is intravenous morphine, scheduled doses of clonidine and increasing doses of gabapentin. It is very uncertain whether aggressive early treatment of these storming episodes affects long-term outcome. Coma and anoxia Coma after resumption of circulation following cardiopulmonary resuscitation has been associated with and explained by severe anoxic–ischaemic injury to the cortical mantle, thalamus, striatum and globus pallidus. Outcome predictions were, for many years, based on a prospective study of the findings on neurological examination and, more importantly, improvement over time.16 17 The distinctions proposed by Levy et al were too clinically useful to dismiss and shifted the conversation.16 Suddenly, 3 days seemed enough (and could be enough) to ascertain whether the patient had a chance to improve. However, a later study found less certainty with this time interval.18 The American Academy of Neurology practice parameter identified poor prognostication but only in a small group of patients.19 We hope no physicians consider employing the 3-day cut-off in these patients without persistent loss of brainstem reflexes or other very good reasons that lead them to doubt the possibility of improvement. Prognostication in coma after cardiopulmonary resuscitation has been studied extensively in recent years and led to the 2014 European Resuscitation Council/European Society of Intensive Care Medicine Guideline.20 Several factors clearly determine a poor prognosis. These include early anoxic brain swelling, an indication of severity (figure 3); diffuse cortical restriction on diffusion-weighted MR scan of brain; absent cortical somatosensory evoked potentials; rising serum neurone-specific enolase21; unreactive and burst–suppression EEG patterns or marked suppression to less than 20 µV,22 burst–suppression EEG time locked with myoclonus status and refractory status epilepticus after CPR (with or without clinical manifestations and with or without myoclonus status). Figure 3 Brain oedema after severe anoxia. There are exceptions, and there are late recoveries with variable outcomes.23–25 However, these occur too infrequently to affect decision-making in this category of patient. Prognostication was perhaps ‘simpler‘ in earlier days of examining patients after a successful cardiopulmonary resuscitation—now, confounders (mostly hypothermia but also a slew of intravenous drugs to support the intervention) are very significant. Drug washout in a severely afflicted patient with associated kidney and liver injury during cardiopulmonary resuscitation remains very difficult to assess and cannot be predicted. Conspicuously lacking in many studies on outcome is information about the neurological examination, use of sedation, neuroimaging and postresuscitation haemodynamic and organ function, which many of us consider crucial in deciphering these patients’ prognoses. Caution is key, and the decision to address the level of care (and what can help the patient) may still have to wait or be regularly revisited. Coma and stroke Both haemorrhagic stroke and ischaemic stroke are heterogeneous disorders, and thus, prognosis is very disease specific.26–28 Coma after a parenchymal (lobar or deep ganglionic) haemorrhage denotes shift from a large-volume destruction of the thalamus or trapping of the ventricle causing obstructive hydrocephalus. Another factor influencing prognosis is the expansion of the clot volume due to anticoagulation. Prognosis in a patient with a deteriorating lobar haematoma depends on whether evacuation is entertained, feasible or delayed. Rapid improvement with resolution of shift attests to that observation. Deep-seated haematomas (putamen and caudate thalamus) cannot be reached surgically, and even placement of a ventricular drain with use of thrombolytic drugs does not improve outcome.29 Haemorrhage in the cerebellum or pons is much less common. Cerebellar haemorrhage with CT evidence of a tight posterior fossa (obliteration of cisterns, tissue displacement upward or downward and tonsillar herniation) will lead to rapid loss of brainstem reflexes without emergent evacuation. Once evaluated, the outcome can be quite good because stance and gait are more affected by injury to efferent fibres than cerebellar structures. Pontine haemorrhages causing coma rarely (if ever) resolve to improvement in functional status and most certainly when they additionally damage the thalamus due to upward extension.30 Coma from ischaemic stroke is based on similar principles. Shift from oedema will not be tolerated unless relieved by a decompression. Haemorrhagic conversion of a large ischaemic stroke does increase mass effect and is a major additional determinant in outcome (figure 4). In a haemispheric stroke (ie, middle cerebral artery), outcome is poor when a decompressive craniectomy is not considered or when performed in the elderly (>60 years).31 32 Early versus late decompressive surgery also influences outcome, and the preponderance of evidence suggests that early decompression before the patient develops clinical signs of deterioration from brainstem involvement will help more. Bithalamic infarcts (from the top-of-the-basilar artery clot) are associated with coma at presentation, but patients may awaken, often after a period of marked fluctuation in alertness. An acute embolus to the basilar artery is devastating (causing infarction of the pons, midbrain and cerebellar haemispheres). Endovascular retrieval of a clot has a high success rate if the admission CT scan is normal. An embolus in the basilar artery that causes coma or locked-in syndrome (caveat non-neurologist) is associated with high mortality and no functional recovery, but there is a chance for substantial recovery if the clot is retrieved. Figure 4 Haemorrhagic infarct with mass effect. Prognostication in aneurysmal subarchnoid hemorrhage is largely unreliable - even in patients who appear moribund soon after the rupture. A comatose patient with aneurysmal subarachnoid haemorrhage can improve rapidly within hours after placement of a ventriculostomy and removal of a temporal lobe clot associated with middle cerebral artery aneurysm. However, if upper brainstem reflexes remain lost after this ‘cerebral resuscitation’, recovery rarely occurs. In many cases, patients presenting with coma have large ventricles filled with blood, and many have rebleeding—the overwhelmingly critical factor in outcome of aneurysmal subarachnoid haemorrhage. The development of later cerebral ischaemia from cerebral vasospasm and inability to control it medically are the major factors in poorer outcomes.33 Older age greatly influences outcome, and in patients over age 80 years, the likelihood of meaningful survival is low.33 34 Nonetheless caution is important because poor grade patients may become good grade patients after active interventions. Coma and CNS infections The outcome for patients with an infection-induced coma (bacterial or viral) depends on the degree of coma and ‘FOUR Score’ on admission. No patient with a ‘FOUR score’ of less than 3 will survive meningitis.35 Causes for this poor prognosis are cerebral oedema, secondary cerebral infarcts (possibly from associated cerebral venous thrombophlebitis and thrombosis) and hydrocephalus. Time to antibiotic treatment36 is a critical determinant, with delay reducing the likelihood of a good functional outcome. Associated sepsis and septic shock, which can result from late recognition and insufficient aggressive intervention, can also worsen the outcome.37 Likely complications include seizures, acute hydrocephalus and septic cerebral infarctions, all of which affect morbidity. Multiorgan failure and septic shock may be the first presentation in a patient with bacterial meningitis. The most important factor associated with poor outcome in bacterial meningitis is systemic illness that manifests itself by tachycardia, hypotension, positive blood cultures, increased erythrocyte sedimentation rate and thrombocytopaenia.38 39 The underlying cause is important, and the odds of an unfavourable outcome are six times higher in patients infected with Streptococcus pneumoniae when compared with patients infected with Neisseria meningitidis. A CT scan of head showing ventriculomegaly or diffuse brain oedema denotes a poor prognosis. Outcome of encephalitis remains indeterminate. The variables include age, duration of disease and level of consciousness. Patients younger than 30 years of age who remain largely alert have a much higher chance of returning to preinfection normal life than older patients with altered consciousness. Encephalitis leading to coma is associated with poor outcome, largely because the available treatments are ineffective.40 41 A small proportion will awaken, and an even smaller proportion will regain independent status. Some encephalitides have no effective treatment and hence a poor outcome. These include rabies encephalitis, many of the fungal infections and, more recently, West Nile virus encephalitis. Many patients with fever or meningitis recover fully, but the more invasive neurological form can cause flaccid paralysis and marked changes in basal ganglia, thalami and brainstem. In general, West Nile virus encephalitis has a 20% mortality rate and acute West Nile virus encephalitis myelitis has a 10%–15% mortality rate (and higher in the elderly). A patient who is comatose from West Nile virus encephalitis has a high risk of mortality. Patients requiring mechanical ventilation may seem to have a poor prognosis, but many can show substantial recovery over a number of years.40 41 These recoveries cannot be adequately predicted. Prognostication in most infectious encephalitides likely should be avoided. Coma and immune-mediated encephalitis There is increasing evidence that, in a large proportion of patients, encephalitis has an autoimmune origin. Patients often present with worsening encephalopathy and status epilepticus. N-methyl-d-aspartate-receptor encephalitis often results in coma from new-onset refractory epilepsy (NORSE), and there is an emerging consensus that patients with NORSE also require immunotherapy. A recent study warned that dyskinetic and stereotypical movements might have been misdiagnosed and overtreated as status epilepticus.42 First-line immunotherapy includes corticosteroids, intravenous immunoglobulin or plasma exchange, with several more options for second-line immune therapies. The outcome in this patient population is always uncertain, and aggressive escalation of therapy with multiple antiepileptic drugs eventually may lead to months of stay in an intensive care unit and protracted improvement. None of the intuitive poor prognostic indicators (MR brain scan abnormalities, refractory status epilepticus and mechanical ventilation for coma) panned out.43 Some patients may develop severe catatonia.44 Coma and neurotoxicity Several types of intoxication and medication overdoses are immediately problematic and may lead to permanent neurological deficits. In many instances, clinical presentation is not easily attributed to a single known toxin. In today’s world, we are confronted with drug abusers, intentional poisoners and, in nearly epidemic proportions, the synthetic opioids. In addition, there is another whole world out there of inhalants containing brain-damaging substances such as aerosols and dry-cleaning fluids. Opioid toxicity—mostly through heroin injection or the use of oxycodone for chronic pain management—can cause permanent injury through anoxic–ischaemic injury. There is a known methadone leucoencephalopathy associated with abnormalities on MR brain imaging that spares the subcortical U-fibres. Usually, this pattern is seen with methadone intoxication.45 Heroin users can remain comatose for weeks with severe white-matter change but sparing of cortex (figure 5). There are a couple extremely important questions that the consulting neurologist should ask. Are there elements of permanent injury, particularly anoxic–ischaemic injury? Do patients need continuous electroencephalography (EEG) monitoring to recognise and manage ongoing seizures? Awakening does occur despite severe white-matter disease on MRI, and even cognition can substantially improve. Nevertheless, prolonged stays in an intensive care unit with tracheostomy and gastrostomy and prolonged gait rehabilitation are common.46 47 Atypical alcohol ingestion (ie, methanol found in commercial products such as windshield washer fluids, deicers, antifreeze, paints, wood stains and glass cleaners) is very problematic and often lethal. Unfortunate cases of survival of intentional carbon monoxide intoxication are occasionally seen. The earliest signs of carbon monoxide poisoning are personality changes with loss of orderliness, snapping at people and outbursts of anxiety but also profound headache and coma when carboxyhaemoglobin concentration increases. Diffuse, haemispheric white-matter involvement on CT scan often develops in comatose patients and patients with long exposure and predicts poor outcome. Figure 5 Heroin-associated leucoencephalopathy. Coma and the unknown There are several circumstances when we do not know (and will never fully know) due to their rarity. These are patients with environmental injuries (eg, electrocution, lightning strikes) and rare disorders such as severe acute metabolic derangements, including hypoglycaemia, leading to permanent coma. In other situations, patients have been found unconscious, and the circumstances cannot be retraced. The best approach remains serial clinical examination and using MR brain imaging to find structural injury and then interpret the severity of injury. A discussion with the family Skilful communication about coma and its consequences is just as important as anything else we do in neurology. This needs a complex core team of nurses, clergy and palliative care professionals with experience in mediating differences of opinion. Fortunately, in many cases—after an adequate explanation—common sense prevails, and consensus between families and the healthcare team can be achieved. Again, prognosis is certainly poor in several conditions (box 2).48 49 Box 2 When the prognosis is certainly poor Massive haemispheric swelling (any cause). Deterioration and sequential loss of brainstem reflexes (any cause). Traumatic brain injury (with primary brainstem and corpus callosum lesions). Pontine haemorrhage with thalamic extension. Embolus to basilar artery (with no reopening). The term ‘futility’ has important connotations, but definitions of medical futility can easily become ‘gobbledy-gook’, and families may wish to continue care even with a very low likelihood of improvement (as long as continuing care does not harm the patient). The quality of the information provided is decisive for many family members. Families may not be fully able to judge the long-term effects of a major neurological injury, and explanations about quality of life should follow. Neurological disability is difficult to describe, and it is even more difficult to know whether the patient can handle these deficits. Just as we would be under similar circumstances, the patient’s family is notoriously unprepared for these situations; the onus is on the experienced neurologist to explain what neurological morbidity and disability entail. Families should clearly understand what we mean by ‘palliative care’, and we should carefully re-explain anything that seems unclear. In general, the aim of palliative care is to reduce suffering and promote comfort resulting in a peaceful and natural death. Conversations should typically occur after 2 weeks have passed or when the patient needs a tracheostomy and gastrostomy. This fork in the road will often lead to reassessment: either support in the hope of improvement or de-escalation to palliative care. We should provide sufficient details about what can be expected for both options. This may be harsh news for the families to absorb: death in a number of days versus prolonged weaning off the ventilator, treatment of multiple complications associated with immobilisation and nursing home placement. The practising neurologist should actively participate in these discussions and develop a rapport with family members. A final word The overall lesson is that we rarely should be surprised by the actual outcome if we take all predictive factors into account. If identified, we should ‘Venn diagram’ the comatose patient with a multitude of serious and often obvious medical conditions. Whether all of this will improve our prediction is uncertain. And then there is the unknown. Reawakening is, of course, not the same as recovery, and long convalescence may reveal pervasive major deficits; for many, traits and skills will never return. We will never have an early, reliable prediction for the previously young and healthy comatose patient with a likely structural injury but no convincing abnormality on MR or other poor clinical indicators. We have limited understanding of the outcome in many patients, and we always will. Machine learning will introduce itself in the coming decade, but machines depend on the questions we pose, and even then it may not be enough.50 Prognostication in coma is not a just fallacy of predetermined outcome or in the eye in the beholder and requires a careful evaluation and some observation time to put the deficit into sharp focus. That is why it is important to acknowledge the neurologist who works beyond simple coma scales or scores. Key points Prognostication in coma can only proceed with full understanding of its cause. Prognostication is not improved using major statistical models. Prognostication works best in identifying the extremes of injury. Prognostication misjudgements often relate to failure to identify confounders. References 1.↵ Wade DT . How often is the diagnosis of the permanent vegetative state incorrect? A review of the evidence. Eur J Neurol 2018;25:619–25.doi:10.1111/ene.13572 OpenUrl 2.↵ Edlow BL , Chatelle C , Spencer CA , et al . Early detection of consciousness in patients with acute severe traumatic brain injury. Brain 2017;140:2399–414.doi:10.1093/brain/awx176 OpenUrl 3.↵ Claassen J , Doyle K , Matory A , et al . Detection of brain activation in unresponsive patients with acute brain injury. N Engl J Med 2019;380:2497–505.doi:10.1056/NEJMoa1812757 OpenUrl 4.↵ Goldfine AM , Victor JD , Conte MM , et al . Determination of awareness in patients with severe brain injury using EEG power spectral analysis. Clin Neurophysiol 2011;122:2157–68.doi:10.1016/j.clinph.2011.03.022 OpenUrlCrossRefPubMed 5.↵ Sutter R , Semmlack S , Kaplan PW . Nonconvulsive status epilepticus in adults - insights into the invisible. Nat Rev Neurol 2016;12:281–93.doi:10.1038/nrneurol.2016.45 OpenUrl 6.↵ Neville TH , Wiley JF , Holmboe ES , et al . Differences between attendings' and fellows' perceptions of futile treatment in the intensive care unit at one academic health center: implications for training. Acad Med 2015;90:324–30.doi:10.1097/ACM.0000000000000617 OpenUrl 7.↵ Racine E , Dion M-J , Wijman CAC , et al . Profiles of neurological outcome prediction among intensivists. Neurocrit Care 2009;11:345–52.doi:10.1007/s12028-009-9225-9 OpenUrlCrossRefPubMed 8.↵ Lingsma HF , Roozenbeek B , Steyerberg EW , et al . Early prognosis in traumatic brain injury: from prophecies to predictions. Lancet Neurol 2010;9:543–54.doi:10.1016/S1474-4422(10)70065-X 9.↵ Maas AIR , Marmarou A , Murray GD , et al . Prognosis and clinical trial design in traumatic brain injury: the IMPACT study. J Neurotrauma 2007;24:232–8.doi:10.1089/neu.2006.0024 10.↵ Perel P , Arango M , Clayton T , et al . Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients. BMJ 2008;336:425–9.doi:10.1136/bmj.39461.643438.25 11.↵ Leitgeb J , Mauritz W , Brazinova A , et al . Effects of gender on outcomes after traumatic brain injury. J Trauma 2011;71:1620–6.doi:10.1097/TA.0b013e318226ea0e OpenUrlPubMed 12.↵ Haghbayan H , Boutin A , Laflamme M , et al . The prognostic value of MRI in moderate and severe traumatic brain injury: a systematic review and meta-analysis. Crit Care Med 2017;45:e1280–8.doi:10.1097/CCM.0000000000002731 OpenUrl 13.↵ Danish SF , Barone D , Lega BC , et al . Quality of life after hemicraniectomy for traumatic brain injury in adults. A review of the literature. Neurosurg Focus 2009;26:E2.doi:10.3171/2009.3.FOCUS945 14.↵ Ho KM , Honeybul S , Lind CRP , et al . Cost-effectiveness of decompressive craniectomy as a lifesaving rescue procedure for patients with severe traumatic brain injury. J Trauma 2011;71:1637–44.doi:10.1097/TA.0b013e31823a08f1 OpenUrlCrossRefPubMed 15.↵ Rabinstein AA , Chung SY , Rudzinski LA , et al . Seizures after evacuation of subdural hematomas: incidence, risk factors, and functional impact. J Neurosurg 2010;112:455–60.doi:10.3171/2009.7.JNS09392 OpenUrlPubMed 16.↵ Levy DE , Bates D , Caronna JJ , et al . Prognosis in nontraumatic coma. Ann Intern Med 1981;94:293–301.doi:10.7326/0003-4819-94-3-293 17.↵ Wijdicks EFM . From clinical judgment to odds: a history of prognostication in anoxic-ischemic coma. Resuscitation 2012;83:940–5.doi:10.1016/j.resuscitation.2012.03.020 OpenUrl 18.↵ Greer DM , Yang J , Scripko PD , et al . Clinical examination for prognostication in comatose cardiac arrest patients. Resuscitation 2013;84:1546–51.doi:10.1016/j.resuscitation.2013.07.028 OpenUrl 19.↵ Wijdicks EFM , Hijdra A , Young GB , et al . Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006;67:203–10.doi:10.1212/01.wnl.0000227183.21314.cd OpenUrlCrossRefPubMed 20.↵ Sandroni C , Cariou A , Cavallaro F , et al . Prognostication in comatose survivors of cardiac arrest: an Advisory statement from the European resuscitation Council and the European Society of intensive care medicine. Intensive Care Med 2014;40:1816–31.doi:10.1007/s00134-014-3470-x OpenUrlCrossRefPubMed 21.↵ Stammet P , Collignon O , Hassager C , et al . Neuron-Specific enolase as a predictor of death or poor neurological outcome after out-of-hospital cardiac arrest and targeted temperature management at 33°C and 36°C. J Am Coll Cardiol 2015;65:2104–14.doi:10.1016/j.jacc.2015.03.538 OpenUrlFREE Full Text 22.↵ Crepeau AZ , Rabinstein AA , Fugate JE , et al . Continuous EEG in therapeutic hypothermia after cardiac arrest: prognostic and clinical value. Neurology 2013;80:339–44.doi:10.1212/WNL.0b013e31827f089d OpenUrlCrossRefPubMed 23.↵ Amorim E , Ghassemi MM , Lee JW , et al . Estimating the false positive rate of absent somatosensory evoked potentials in cardiac arrest prognostication. Crit Care Med 2018;46:e1213–21.doi:10.1097/CCM.0000000000003436 OpenUrl 24.↵ Beekman RB , Greer DM , Brooks DC , et al . Clinical Reasoning: Prognostication after cardiac arrest: what do we really know? Neurology 2017;89:e239–44.doi:10.1212/WNL.0000000000004649 OpenUrl 25.↵ Rey A , Rossetti AO , Miroz J-P , et al . Late awakening in survivors of postanoxic coma: early neurophysiologic predictors and association with ICU and long-term neurologic recovery. Crit Care Med 2019;47:85–92.doi:10.1097/CCM.0000000000003470 OpenUrl 26.↵ Balami JS , Buchan AM . Complications of intracerebral haemorrhage. Lancet Neurol 2012;11:101–18.doi:10.1016/S1474-4422(11)70264-2 27.↵ Huang P , Lin F-C , Su Y-F , et al . Predictors of in-hospital mortality and prognosis in patients with large hemispheric stroke receiving decompressive craniectomy. Br J Neurosurg 2012;26:504–9.doi:10.3109/02688697.2011.641614 OpenUrlPubMed 28.↵ Rost NS , Smith EE , Chang Y , et al . Prediction of functional outcome in patients with primary intracerebral hemorrhage: the FUNC score. Stroke 2008;39:2304–9.doi:10.1161/STROKEAHA.107.512202 29.↵ Hanley DF , Thompson RE , Rosenblum M , et al . Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet 2019;393:1021–32.doi:10.1016/S0140-6736(19)30195-3 OpenUrl 30.↵ Huang K , Ji Z , Sun L , et al . Development and validation of a grading scale for primary pontine hemorrhage. Stroke 2017;48:63–9.doi:10.1161/STROKEAHA.116.015326 31.↵ Alexander P , Heels-Ansdell D , Siemieniuk R , et al . Hemicraniectomy versus medical treatment with large MCA infarct: a review and meta-analysis. BMJ Open 2016;6:e014390.doi:10.1136/bmjopen-2016-014390 32.↵ Beez T , Munoz-Bendix C , Steiger H-J , et al . Decompressive craniectomy for acute ischemic stroke. Crit Care 2019;23.doi:10.1186/s13054-019-2490-x 33.↵ Suwatcharangkoon S , De Marchis GM , Witsch J , et al . Medical treatment failure for symptomatic vasospasm after subarachnoid hemorrhage threatens long-term outcome. Stroke 2019;50:1696–702.doi:10.1161/STROKEAHA.118.022536 OpenUrl 34.↵ Shimamura N , Munakata A , Ohkuma H . Current management of subarachnoid hemorrhage in advanced age. Acta Neurochir Suppl 2011;110:151–5.doi:10.1007/978-3-7091-0356-2_27 35.↵ van Ettekoven CN , Brouwer MC , Bijlsma MW , et al . The four score as predictor of outcome in adults with bacterial meningitis. Neurology 2019;92:e2522–6.doi:10.1212/WNL.0000000000007601 OpenUrl 36.↵ Køster-Rasmussen R , Korshin A , Meyer CN . Antibiotic treatment delay and outcome in acute bacterial meningitis. J Infect 2008;57:449–54.doi:10.1016/j.jinf.2008.09.033 37.↵ Weisfelt M , van de Beek D , Spanjaard L , et al . A risk score for unfavorable outcome in adults with bacterial meningitis. Ann Neurol 2008;63:90–7.doi:10.1002/ana.21216 OpenUrlCrossRefPubMed 38.↵ Auburtin M , Porcher R , Bruneel F , et al . Pneumococcal meningitis in the intensive care unit: prognostic factors of clinical outcome in a series of 80 cases. Am J Respir Crit Care Med 2002;165:713–7.doi:10.1164/ajrccm.165.5.2105110 39.↵ Fitch MT , van de Beek D . Emergency diagnosis and treatment of adult meningitis. Lancet Infect Dis 2007;7:191–200.doi:10.1016/S1473-3099(07)70050-6 40.↵ Hawkes MA , Carabenciov ID , Wijdicks EFM , et al . Outcomes in patients with severe West Nile Neuroinvasive disease. Crit Care Med 2018;46:e955–8.doi:10.1097/CCM.0000000000003257 OpenUrl 41.↵ Hawkes MA , Carabenciov ID , Wijdicks EFM , et al . Critical West Nile Neuroinvasive disease. Neurocrit Care 2018;29:47–53.doi:10.1007/s12028-017-0500-x OpenUrl 42.↵ Schubert J , Brämer D , Huttner HB , et al . Management and prognostic markers in patients with autoimmune encephalitis requiring ICU treatment. Neurol Neuroimmunol Neuroinflamm 2019;6:e514.doi:10.1212/NXI.0000000000000514 43.↵ Broadley J , Seneviratne U , Beech P , et al . Prognosticating autoimmune encephalitis: a systematic review. J Autoimmun 2019;96:24–34.doi:10.1016/j.jaut.2018.10.014 OpenUrl 44.↵ Rogers JP , Pollak TA , Blackman G , et al . Catatonia and the immune system: a review. Lancet Psychiatry 2019;6:620–30.doi:10.1016/S2215-0366(19)30190-7 OpenUrl 45.↵ Salgado RA , Jorens PG , Baar I , et al . Methadone-Induced toxic leukoencephalopathy: MR imaging and Mr proton spectroscopy findings. AJNR Am J Neuroradiol 2010;31:565–6.doi:10.3174/ajnr.A1889 46.↵ Achamallah N , Wright RS , Fried J . Chasing the wrong dragon: a new presentation of heroin-induced toxic leukoencephalopathy mimicking anoxic brain injury. J Intensive Care Soc 2019;20:80–5.doi:10.1177/1751143718774714 OpenUrl 47.↵ Cordova JP , Balan S , Romero J , et al . 'Chasing the dragon': new knowledge for an old practice. Am J Ther 2014;21:52–5.doi:10.1097/MJT.0b013e31820b8856 OpenUrl 48.↵ Wijdicks EFM . Communicating prognosis. New York: Oxford University Press, 2014. 49.↵ Wijdicks EFM . The comatose patient. Second edition. Oxford University Press, 2014. 50.↵ Deo RC . Machine learning in medicine. Circulation 2015;132:1920–30.
No comment yet.
Your new post is loading...
Scooped by Nesrin Shaheen
Scoop.it!

World Encephalitis Day 2020 Encephalitis Conference -- Encephalitis Global

World Encephalitis Day 2020 Encephalitis Conference -- Encephalitis Global | AntiNMDA | Scoop.it
World Encephalitis Day 2020 Encephalitis Conference. Encephalitis Global has been proud to offer an annual Encephalitis Conference welcoming survivors and caregivers to spend the weekend in a venue where everyone understood the life-altering impact of encephalitis.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

The princess and the p-value: A case report of suspected autoimmune encephalitis and functional neurological disorder in a pediatric patient: Applied Neuropsychology: Child: Vol 9, No 1

The princess and the p-value: A case report of suspected autoimmune encephalitis and functional neurological disorder in a pediatric patient: Applied Neuropsychology: Child: Vol 9, No 1 | AntiNMDA | Scoop.it
AbstractAutoimmune encephalitis is a rapidly evolving area of study in pediatric populations, and functional neurological symptom disorders are under-studied in children. Differential diagnosis amo...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Spanish Pediatric Anti-MOG Study Group Discovery Could Accelerate Diagnosis & Treatment of Children with Life-Threatening Neurological Diseases

Spanish Pediatric Anti-MOG Study Group Discovery Could Accelerate Diagnosis & Treatment of Children with Life-Threatening Neurological Diseases | AntiNMDA | Scoop.it
In observational research, a multi-center team of investigators called the “Spanish Pediatric Anti-MOG Study Group” discovered that 85% of children in a...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Leucine-rich glioma-inactivated protein 1 (LGI-1) mediated limbic encephalitis associated with syndrome of inappropriate antidiuretic hormone secretion: a case report | Read by QxMD

Leucine-rich glioma-inactivated protein 1 (LGI-1) mediated limbic encephalitis associated with syndrome of inappropriate antidiuretic hormone secretion: a case report | Read by QxMD | AntiNMDA | Scoop.it
Leucine-rich glioma-inactivated protein 1 (LGI-1) mediated limbic encephalitis associated with syndrome of inappropriate antidiuretic hormone secretion: a case report Emily Whiles, Hareesh Joshi, Prachi Prachi, Venkaiah Kavuri, Satyanarayana V Sagi Oxford Medical Case Reports 2020, 2020 (1): omz136 Autoantibodies to leucine-rich glioma-inactivated protein 1 (LGI-1) are associated with inflammation of the limbic system. Faciobrachial dystonic seizures are pathognomonic for LGI1-antibiodies and their treatment with immunotherapy is effective in seizure control with a potential to prevent cognitive decline. We report a 57-year-old man who presented to the emergency department with recurrent seizures, visual hallucinations and severe memory impairment over a seven-week period; he reported a background of alcohol excess. Initial investigations revealed hyponatremia, indicating syndrome of inappropriate anti-diuretic hormone secretion. Magnetic resonance imaging of the brain revealed bilateral asymmetrical high-T2 and low-T1 signal in the medial temporal lobes. Serum immunofluorescence assay tested positive for LGI-1 antibody. Patient responded to treatment with levetiracetam, intravenous methylprednisolone and five plasma exchange sessions. Patient remains on a maintenance dose of prednisolone and azathioprine. It is imperative that clinicians recognize signs of autoimmune encephalitis in order to curb long-term sequelae and improve clinical outcomes. Read this article (multiple options) Discussion You are not logged in. Sign Up or Log In to join the discussion. Trending Papers Current management of supraventricular tachycardias: the 2019 ESC Guidelines. Thomas F Lüscher European Heart Journal 2020 February 1, 41 (5): 607-609 Drug treatment options for the 2019-new coronavirus (2019-nCoV). Hongzhou Lu Bioscience Trends 2020 January 28 Highlights in heart failure. Daniela Tomasoni, Marianna Adamo, Carlo Mario Lombardi, Marco Metra ESC Heart Failure 2019, 6 (6): 1105-1127 Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Scott L Weiss, Mark J Peters, Waleed Alhazzani, Michael S D Agus, Heidi R Flori, David P Inwald, Simon Nadel, Luregn J Schlapbach, Robert C Tasker, Andrew C Argent, Joe Brierley, Joseph Carcillo, Enitan D Carrol, Christopher L Carroll, Ira M Cheifetz, Karen Choong, Jeffry J Cies, Andrea T Cruz, Daniele De Luca, Akash Deep, Saul N Faust, Claudio Flauzino De Oliveira, Mark W Hall, Paul Ishimine, Etienne Javouhey, Koen F M Joosten, Poonam Joshi, Oliver Karam, Martin C J Kneyber, Joris Lemson, Graeme MacLaren, Nilesh M Mehta, Morten Hylander Møller, Christopher J L Newth, Trung C Nguyen, Akira Nishisaki, Mark E Nunnally, Margaret M Parker, Raina M Paul, Adrienne G Randolph, Suchitra Ranjit, Lewis H Romer, Halden F Scott, Lyvonne N Tume, Judy T Verger, Eric A Williams, Joshua Wolf, Hector R Wong, Jerry J Zimmerman, Niranjan Kissoon, Pierre Tissieres Pediatric Critical Care Medicine 2020, 21 (2): e52-e106
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Autoimmune encephalitis management: MS centers and beyond. - PubMed - NCBI

Autoimmune encephalitis management: MS centers and beyond. - PubMed - NCBI | AntiNMDA | Scoop.it
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Different FDG-PET metabolic patterns of anti-AMPAR and anti-NMDAR encephalitis: Case report and literature review | Read by QxMD

Different FDG-PET metabolic patterns of anti-AMPAR and anti-NMDAR encephalitis: Case report and literature review | Read by QxMD | AntiNMDA | Scoop.it
JOURNAL ARTICLE Different FDG-PET metabolic patterns of anti-AMPAR and anti-NMDAR encephalitis: Case report and literature review Yi-Chia Wei, Jing-Ren Tseng, Chia-Lun Wu, Feng-Chieh Su, Wei-Chieh Weng, Chih-Chin Hsu, Kai-Hsiang Chang, Chun-Feng Wu, Ing-Tsung Hsiao, Ching-Po Lin Brain and Behavior 2020 January 27, : e01540 INTRODUCTION: 18 F-fluorodeoxyglucose (FDG)-PET metabolic patterns of brain differ among autoimmune encephalitis with different neuronal surface antigens. In this case report, we compared the topographical relationship of cerebral glucose metabolism and antigen distribution in the patients with anti-NMDAR and anti-AMPAR encephalitis. Literature review summarized the common features of brain metabolism of autoimmune encephalitis. METHODS: The cerebral glucose metabolism was evaluated by FDG-PET/CT during acute-to-subacute stage of autoimmune encephalitis and after treatment. The stereo and quantitative analysis of cerebral metabolism used standardized z-score and visualized on three-dimensional stereotactic surface projection. To map NMDAR and AMPAR in human brain, we adopted genetic atlases from the Allen Institute and protein atlases from Zilles's receptor densities. RESULTS: The three-dimensional stereotactic surface projection displayed frontal-dominant hypometabolism in a 66-year-old female patient with anti-AMPAR encephalitis and occipital-dominant hypometabolism in a 29-year-old female patient with anti-NMDAR encephalitis. Receptor density maps revealed opposite frontal-occipital gradients of AMPAR and NMDAR, which reflect reduced metabolism in the correspondent encephalitis. FDG-PET hypometabolic areas possibly represent receptor hypofunction with spatial correspondence to receptor distributions of the autoimmune encephalitis. The reversibility of hypometabolism was in line with patients' cognitive improvement. The literature review summarized six features of metabolic anomalies of autoimmune encephalitis: (a) temporal hypometabolism, (b) frontal hypermetabolism and (c) occipital hypometabolism in anti-NMDAR encephalitis, (d) hypometabolism in association cortices, (e) sparing of unimodal primary motor cortex, and (e) reversibility in recovery. CONCLUSIONS: The distinct cerebral hypometabolic patterns of autoimmune encephalitis were representative for receptor hypofunction and topographical distribution of antigenic receptors. The reversibility of hypometabolism marked the clinical recovery of autoimmune encephalitis and made FDG-PET of brain a valuable diagnostic tool. Discussion You are not logged in. Sign Up or Log In to join the discussion. Related Papers Decreased occipital lobe metabolism by FDG-PET/CT: An anti-NMDA receptor encephalitis biomarker. John C Probasco, Lilja Solnes, Abhinav Nalluri, Jesse Cohen, Krystyna M Jones, Elcin Zan, Mehrbod S Javadi, Arun Venkatesan Neurology® Neuroimmunology & Neuroinflammation 2018, 5 (1): e413 Cerebral (18)FluoroDeoxy-Glucose Positron Emission Tomography in paediatric anti N-methyl-D-aspartate receptor encephalitis: A case series. Stanislas Lagarde, Anne Lepine, Emilie Caietta, Florence Pelletier, José Boucraut, Brigitte Chabrol, Mathieu Milh, Eric Guedj Brain & Development 2016, 38 (5): 461-70 Fluorodeoxyglucose positron emission tomography in anti-N-methyl-D-aspartate receptor encephalitis: distinct pattern of disease. Frank Leypoldt, Ralph Buchert, Ingo Kleiter, Jörg Marienhagen, Mathias Gelderblom, Tim Magnus, Josep Dalmau, Christian Gerloff, Jan Lewerenz Journal of Neurology, Neurosurgery, and Psychiatry 2012, 83 (7): 681-6 Metabolic topography of autoimmune non-paraneoplastic encephalitis. Madhavi Tripathi, Manjari Tripathi, Shambo Guha Roy, Girish Kumar Parida, Kavish Ihtisham, Deepa Dash, Nishikant Damle, Shamim Ahmed Shamim, Chandrasekhar Bal Neuroradiology 2018, 60 (2): 189-198 Diagnostic Value of 18 F-FDG PET/CT Versus MRI in the Setting of Antibody-Specific Autoimmune Encephalitis. Lilja B Solnes, Krystyna M Jones, Steven P Rowe, Puskar Pattanayak, Abhinav Nalluri, Arun Venkatesan, John C Probasco, Mehrbod S Javadi Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine 2017, 58 (8): 1307-1313 Hypoglutamatergic state is associated with reduced cerebral glucose metabolism in anti-NMDA receptor encephalitis: a case report. Dominique Endres, Evgeniy Perlov, Oliver Stich, Sebastian Rauer, Simon Maier, Zora Waldkircher, Thomas Lange, Irina Mader, Philipp Tobias Meyer, Ludger Tebartz van Elst BMC Psychiatry 2015, 15: 186 Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis. John C Probasco, Lilja Solnes, Abhinav Nalluri, Jesse Cohen, Krystyna M Jones, Elcin Zan, Mehrbod S Javadi, Arun Venkatesan Neurology® Neuroimmunology & Neuroinflammation 2017, 4 (4): e352 Semi-quantitative analysis of cerebral FDG-PET reveals striatal hypermetabolism and normal cortical metabolism in a case of VGKCC limbic encephalitis. Patrick Moloney, Ruth Boylan, Marwa Elamin, Sean O'Riordan, Ronan Killeen, Christopher McGuigan Neuroradiology Journal 2017, 30 (2): 160-163 Caspr2 antibody-associated limbic encephalitis: contribution of visual aided analysis of 18 F-FDG PET images using normal database comparison. Liset Sánchez-Ordúz, Jaime Gállego Pérez-Larraya, Fabiana Grisanti, María Centeno, Javier Arbizu Revista Española de Medicina Nuclear e Imagen Molecular 2019 November 26 Monitoring the Effect of Immunotherapy in Autoimmune Limbic Encephalitis Using 18F-FDG PET. Cristina Trevino-Peinado, Javier Arbizu, Pablo Irimia, Mario Riverol, Eduardo Martínez-Vila Clinical Nuclear Medicine 2015, 40 (9): e441-3
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

The Anti-NMDA Receptor Encephalitis Foundation Newsletter

The Anti-NMDA Receptor Encephalitis Foundation Newsletter | AntiNMDA | Scoop.it
World Encephalitis Day 2020 Encephalitis Conference — Encephalitis Global From www.prlog.org –...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

A potential treatment for life-threatening neurological diseases

A potential treatment for life-threatening neurological diseases | AntiNMDA | Scoop.it
A group of life-threatening neurological conditions affecting children has been linked to an antibody that points to potential treatment, according to an observational multicenter study involving 535 children with central ...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Leucine-rich glioma-inactivated protein 1 (LGI-1) mediated limbic encephalitis associated with syndrome of inappropriate antidiuretic hormone secre... - PubMed - NCBI

Leucine-rich glioma-inactivated protein 1 (LGI-1) mediated limbic encephalitis associated with syndrome of inappropriate antidiuretic hormone secre... - PubMed - NCBI | AntiNMDA | Scoop.it
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

'I went from being a healthy young woman to being locked up on a psychiatric ward for three months' - Lincolnshire Live

'I went from being a healthy young woman to being locked up on a psychiatric ward for three months' - Lincolnshire Live | AntiNMDA | Scoop.it
She is now campaigning for more awareness of Anti-NMDA receptor encephalitis...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Intrathecal B-cell activation in LGI1 antibody encephalitis | Neurology Neuroimmunology & Neuroinflammation

Intrathecal B-cell activation in LGI1 antibody encephalitis | Neurology Neuroimmunology & Neuroinflammation | AntiNMDA | Scoop.it
Abstract Objective To study intrathecal B-cell activity in leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis. In patients with LGI1 antibodies, the lack of CSF lymphocytosis or oligoclonal bands and serum-predominant LGI1 antibodies suggests a peripherally initiated immune response. However, it is unknown whether B cells within the CNS contribute to the ongoing pathogenesis of LGI1 antibody encephalitis. Methods Paired CSF and peripheral blood (PB) mononuclear cells were collected from 6 patients with LGI1 antibody encephalitis and 2 patients with other neurologic diseases. Deep B-cell immune repertoire sequencing was performed on immunoglobulin heavy chain transcripts from CSF B cells and sorted PB B-cell subsets. In addition, LGI1 antibody levels were determined in CSF and PB. Results Serum LGI1 antibody titers were on average 127-fold higher than CSF LGI1 antibody titers. Yet, deep B-cell repertoire analysis demonstrated a restricted CSF repertoire with frequent extensive clusters of clonally related B cells connected to mature PB B cells. These clusters showed intensive mutational activity of CSF B cells, providing strong evidence for an independent CNS-based antigen-driven response in patients with LGI1 antibody encephalitis but not in controls. Conclusions Our results demonstrate that intrathecal immunoglobulin repertoire expansion is a feature of LGI1 antibody encephalitis and suggests a need for CNS-penetrant therapies. Glossary BBB=blood-brain barrier; BCR=B-cell receptor; cDNA=complementary DNA; DIRS=deep B-cell immune repertoire sequencing; IgD=immunoglobulin D; IgG=immunoglobulin G; IgM=immunoglobulin M; LGI1=leucine-rich, glioma-inactivated 1; NMDAR=NMDA receptor; PB=peripheral blood; SHM=somatic hypermutation; SM=switched memory; UCSF=University of California, San Francisco; VH=heavy chain variable region Leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis is characterized by rapidly progressive cognitive impairment, frequent seizures, most characteristically faciobrachial dystonic seizures, psychiatric disturbances, and sleep alterations.1,2 These distinctive clinical features, alongside in vitro and in vivo studies,3,4 and the often rapid response of seizures to immunotherapies all strongly suggest that LGI1 antibodies are pathogenic.2 However, LGI1 antibody encephalitis can often result in residual cognitive impairment and neurologic disability: this represents an unmet medical need.2,5 Although CSF LGI1 antibodies are detected in around 90% of cases, this condition is infrequently associated with CSF lymphocytosis or oligoclonal bands.2,6,7 Therefore, the CSF B-cell response has received limited consideration as contributor to pathogenesis or as a potential therapeutic target. Indeed, very little is known about B cells that participate in the autoimmune response against LGI1, either in the periphery or CSF. Here, we applied deep B-cell immune repertoire sequencing (DIRS) on sorted peripheral blood (PB) B-cell subsets and CSF and found strong evidence for intrathecal antigen-driven immune responses in patients with LGI1 antibody encephalitis. These observations inform disease biology and suggest CNS B cells as a candidate therapeutic target in these patients. Methods Patient samples Six patients with LGI1 antibody encephalitis from the University of California, San Francisco (UCSF) Autoimmune Encephalopathy Clinic underwent collection of paired PB (40 mL) and 10–25 mL of CSF. B-cell subsets were isolated as described previously.8 As controls, 2 patients with other noninflammatory neurologic diseases from the same center were included in the study and their PB and CSF samples collected accordingly. Standard protocol approvals, registrations, and patient consents The study was approved by the Institutional Review Board of the UCSF. Written informed consent was obtained from all participants in the study. Cell staining and sorting Ficoll-density separated peripheral blood mononuclear cells were stained with the following antibodies: CD19 (APC Cy7), immunoglobulin D (IgD) (PE Cy7), CD27 (Qdot605), CD38 (PerCP Cy5.5), and CD3 (Pacific blue) as previously described.8 B-cell subsets were sorted using a FACS Aria III (BD Biosciences, Franklin Lakes, NJ) into naive (CD19+IgD+CD27−), unswitched memory (CD19+IgD+CD27+), switched memory (CD19+IgD−CD27+CD38−), double negative (CD19+IgD−CD27−), and plasmablasts/plasma cells (CD19+IgD−CD27hiCD38hi). Sorted cells were immediately lyzed in RLT buffer (RNeasy kit; Qiagen, Hilden, Germany) and stored at −80°C. To preserve the far lower CSF lymphocyte frequencies, unfractionated pelleted CSF cells were studied. Immunoglobulin messenger RNA amplification and immunoglobulin repertoire sequencing Sequencing work flow was performed as previously described,9 with modifications to sequence human samples. In brief, total RNA was isolated from CSF cells and PB B-cell subsets, followed by reverse transcription into complementary DNA (cDNA). Next, immunoglobulin G (IgG) heavy chain variable region (VH) and immunoglobulin M (IgM) VH were amplified by PCR using the following primers: IgG 3′ primer: 5′-GGGAAGACSGATGGGCCCTTGGTGG-3′; IgM 3′ primer: 5′-GCTCGTATCCGACGGG-3′; an equimolar mix of 7 VH family 5′ primers: VH1: 5′-GAARRTYTCCTGCAAGGYWTC-3′; VH2: 5′-CACRCTGACCTGCACCKTCTC-3′; VH3: 5′-KARACTCTCCTGTRCAGCCTB-3′; VH4: 5′-GTCCCTCACCTGCRCTGTCTM-3′; VH5: 5′-GARGATCTCCTGTAAGGGTTC-3′; VH6: 5′-CTCACTCACCTGTGCCATCTC-3′; VH7: 5′-GAAGGTTTCCTGCAAGGCTTC-3′. PCR conditions were (1) 95°C, 60 seconds; (2) 95°C, 30 seconds; 66.6°C, 30 seconds; 72°C, 60 seconds (33 or 45 cycles); and (3) 72°C, 7 minutes. Specific PCR products were gel purified and mixed to create 15 pM cDNA libraries, which were analyzed by Ion Torrent semiconductor sequencing. Sequence analysis IGHV and IGHJ gene segment usage, complementarity determining region (CDR)1-3 amino acid sequence, and number of somatic hypermutation (SHM) events were determined as previously described.8,9 Briefly, CDR3 amino acid sequences were determined using a custom-made pipeline adapted from the AbMining tool,10 and identified CDR3 regions were related to IGHV and IGHJ germline genes using IgBlast. To calculate SHM profiles, sequencing reads with identical CDR1 to CDR3 nucleotide sequences were grouped as nonredundant (unique) reads, and SHMs were quantified for this entire region based on the alignment of reads with germline gene segments. Compartmental connectivity via bicompartmental clustering of IgM-VH or IgG-VH from CSF and PB B-cell subsets was performed as previously described.8 Briefly, clonally related Ig-VH sequences were identified based on H-CDR3 similarity (hamming distance of H-CDR3 amino acid sequence less than 2) and usage of identical Ig germline segments. For lineage analysis, only Ig-VH sequences with in-frame H-CDR3 and which spanned at least from the 5′ end of H-CDR1 to the 3′ end of H-CDR3 with a contiguous reading frame were used; IgTree11 (kindly provided by Dr. Ramit Mehr, Bar-Ilan University, Ramat-Gan, Israel) was used to map the lineage.8 Putative germline nodes are inferred, and lineage intermediates not found by DIRS were calculated by IgTree. Data availability All next-generation sequencing data and computer code other than software packages are available from the corresponding author on reasonable request. Results Serum LGI1 antibodies titers were on average 127-fold higher than CSF LGI1 antibody titers by live cell–based assay using a membrane-tethered LGI1 construct in all 6 patients with LGI1 antibody encephalitis (table), none of whom were asymptomatic at follow-up.12 None of the 6 patients showed a CSF lymphocytosis or oligoclonal bands on routine CSF analysis. There was no abnormal enhancement on brain MRI in any of the patients following the administration of gadolinium, consistent with no substantial blood-brain barrier (BBB) opening. DIRS of IgG-VH and IgM-VH was performed from paired CSF and B-cell subsets sorted from peripheral blood mononuclear cell samples of the 6 LGI1 antibody encephalitis patients, and a median of 600,707 sequences per sample (range 165,369–1,586,974) were generated. As expected, circulating naive B cells had limited somatic mutations and as cells acquired the postgerminal center marker CD27, and class-switched to IgG, mutations accumulated (figure 1A). These findings are a validation that DIRS reliably reflects the conventional B-cell maturation stages and suggests that CSF B cells in LGI1 encephalitis have undergone antigen-driven maturation (figure 1A). View inline View popup Table Patient characteristics of 6 patients with LGI1 encephalitis and 2 controls (bottom 2 rows) Figure 1 In patients with leucine-rich, glioma-inactivated 1 antibody encephalitis, deep immune repertoire sequencing of the immunoglobulin heavy chain variable region (Ig-VH) shows connectivity of class-switched mature peripheral blood (PB) B cells to clonally expanded CSF B cells/clusters One representative patient of 6 patients is shown in A–D. (A) Cumulative number of somatic mutations (x-axis) in the IGHV gene nucleic acid sequence excluding the CDR3 region in nonredundant sequences (count; y-axis) of sorted PB B-cell subsets and CSF B cells are shown for IgM (left panels) and IgG (right panels). (B) Connectivity of the various PB and CSF B-cell compartments based on clonal relationship is illustrated. While the size of the boxes correlates with the number of reads in each compartment, the thickness of the connecting line correlates with the number of related sequences between the 2 compartments it connects. For better display, all lines connecting to the CSF IgG compartment are depicted in red, whereas all others are in black. IgG = immunoglobulin G; IgM = immunoglobulin M; N = naive; PC = plasmablast/plasma cell; SM = switched memory; USM = unswitched memory. (C) All clusters of clonally related Ig-VH that have at least 1 sequence in one of the PB compartments and 1 in the CSF compartments (shared PB and CSF clusters) are depicted with their respective size (number of nonredundant sequences) on the y-axis. (D) Frequency of used IGHV genes in the IgG CSF, PB plasmablast/plasma cell, and PB SM cell subsets. Overall, across all 6 patients, all B-cell subsets of IgG and IgM isotypes showed high degrees of sequence connectivity in both PB and CSF compartments (figure 1B). A striking link existed between PB IgG-expressing SM cells/plasmablasts/plasma cells and the IgG-expressing CSF B cells, suggesting that class-switched mature B-cell compartments are consistently connected across the BBB. The CSF B cells often represented a discrete number of highly expanded clusters (figure 1C). Indeed, this restriction of the CSF B-cell repertoire was also evident at the level of the heavy V gene family usage. In contrast to the peripheral SM and plasmablast/plasma cell IgG compartments, which were diverse and highly comparable, the CSF IgG repertoire was distinct and restricted (figure 1D). Next, clusters shared between the CSF and PB were examined more closely. These shared CSF/PB clusters on average had 990.3 (range 110–1,749) unique sequences. In this analysis, each unique sequence was represented by a dot and a line joining neighboring sequences represented a mutational (Hamming) distance of 1 in their CDR3 region (figure 2A). By definition, there is at least 1 PB (red) and 1 CSF (blue) sequence in each cluster. Many shared clusters were dominated by peripheral B cells and were related to only a small number of CSF B cells. Also, of interest, several clusters highly dominated by CSF sequences were apparent and often showed a PB sequence in the center, representing a more proximal sequence with fewer mutations from which surrounding CSF sequences may have descended. More detailed analysis of Ig lineage trees from clonally related CSF IgG-VH demonstrated intensive mutational activity, again suggesting intrathecal SHM (figure 2B). Figure 2 Intrathecal somatic hypermutation in patients with leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis (A) Data from 1 representative patient of 6 LGI1 patients showing all clusters of clonally related immunoglobulin heavy chain variable region, which are shared between peripheral blood (PB) and CSF B cells. Each red dot represents ≥1 identical PB sequence, and each blue dot ≥1 identical CSF sequence. Two dots connected by a line differ from each other by a Hamming distance of 1 in their CDR3 region on the nucleotide sequence level. Clusters of related sequences are grouped together. (B) Two Ig lineage trees of CSF B cells from 1 patient are shown. Each dot represents 1 sequence, and its size correlates with the number of times this sequence could be found. Two dots connected by a line differ from each other by 1 nucleotide in the CDR3 region unless marked otherwise. Putative germline nodes are labeled; lineage intermediates not found in the sequencing data were calculated and are labeled in gray. In contrast to all LGI1 antibody encephalitis cases, 2 patients ultimately diagnosed with noninflammatory neurologic diseases (1 with headache and 1 with chronic migraine), which were analyzed following the same protocol, did not show comparable intrathecal B-cell activity. In 1 of the 2 controls, we were unable to amplify enough CSF IgG RNA for sequencing, indicating very few CSF IgG transcripts; in the other, we were able to detect 43 unique sequences in the CSF, which were parts of shared CSF/PB clusters compared with 990.3 (mean; range 110–1,749) in LGI1 antibody encephalitis. Shared clusters in the control were overwhelmingly PB dominated and had on average 1.2 CSF IgG sequences (range 1–3), whereas shared clusters in patients with LGI1 antibody encephalitis had larger CSF fractions with a mean of 8.1 CSF IgG sequences (range: mean value per patient 3.4–11.9; minimum/maximum value per patient across all 6 patients 1/465). Taken together, DIRS demonstrated high sensitivity in detecting an intrathecal B-cell response and marked interconnectivity between the PB and CSF compartments in LGI1 antibody encephalitis, particularly of the more mature B-cell subsets. However, the antigen specificity of the clonally expanded intrathecal B cells remains unclear. Peripheral B-cell expansions infrequently reached the CSF, but those which did commonly lead to intrathecal B-cell expansions, consistent with secondary intrathecal B-cell receptor (BCR) diversification in LGI1 antibody encephalitis but not in noninflammatory controls. Discussion Here, we examined the potential paradox between the limited detectable CSF activity in routine clinical assessments (e.g., CSF cell count and oligoclonal bands), alongside the presence of pathogenic CNS-active autoantibodies in patients with LGI1 antibody encephalitis. For the first time, using DIRS, we demonstrate highly active intrathecal B-cell activity in LGI1 antibody patients and show that B-cell repertoires, particularly from postgerminal center B cells on both sides of the BBB, may actively mutate and mature in patients with LGI1 antibody encephalitis. Because, for methodological reasons, our study could not address the antigen specificity of the intrathecal B-cell response, it remains to be determined whether these expanded clones recognize LGI1-specific epitopes, and it is likely that some of these represent non–LGI1-specific B cells. LGI1-specific CSF B cells are more likely to exist in the patients in which intrathecal LGI1 antibodies were detectable. However, it cannot be excluded that LGI1 antibodies have passively diffused to the CSF. In our studies, we found PB plasmablast/plasma cell IgG-VHs, which underwent SHM and were related to expanded clusters of CSF B cells. This pattern closely resembles findings in MS, suggesting that it may be a generic mechanism across CNS autoimmune conditions,8,9,13 and accordingly, we did not observe this phenomenon in noninflammatory controls. Yet, these observations appear different to the more limited intrathecal expansions observed in neuromyelitis optica spectrum disorder and the very low mutational load in CSF B cells from patients with NMDA receptor (NMDAR) antibody encephalitis.14,15 Hence, it may be that several different immunologic mechanisms operate across these autoantibody-mediated conditions. Our study did not aim to examine the antigen-specific population or correlate intrathecal B-cell responses with clinical outcome. Of interest, it has recently been observed that intrathecal LGI1 antibody synthesis correlates with a poorer prognosis.16 However, the lack of CSF LGI1 antibodies in some of our patients with striking intrathecal SHM may suggest that DIRS provides a more sensitive measure of B-cell activity. In general, the majority of autoimmune encephalitis syndromes are considered to be IgG mediated.2,7,16,17 However, we also found evidence for extensively activated IgM-expressing peripheral B cells, which share similar or identical BCR heavy chains to intrathecal IgG-expressing B cells. The immunopathologic relevance of this IgM response is unknown, but may indicate an ongoing germinal center reaction-mediated stimulation of B cells as has been proposed in patients with NMDAR antibody encephalitis, where IgM NMDAR-reactive autoantibodies can be detected.18,19 A major question is whether interrupting these responses could potentially mitigate disease activity, prevent relapses, and improve long-term cognitive outcomes. Yet, only a subset of patients with LGI1 antibody encephalitis have been reported to respond favorably to rituximab, which targets—mainly peripheral—CD20-expressing B cells and has little effect on LGI1 antibody production.20 Our findings suggest that plasmablasts and plasma cells (which do not express CD20) are active in the CSF, and therefore, novel drugs that actively target these prolific protein synthesizers in the CNS compartment might be more effective than selective anti-CD20 treatments. Conversely, given that affinity maturation is an ongoing process in LGI1 antibody encephalitis and could result in increasingly efficient pathogenic antibodies, therapeutic depletion of CD20-expressing B-cell populations early in this disease might prevent development of chronic or progressive clinical phenotypes. Accordingly, early diagnosis of intrathecal immune activation in patients with mild clinical signs would be highly desirable. Study funding The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). Disclosure K.L.-H. has received research support (to TUM) from Novartis, honoraria from Novartis and F. Hoffmann-La Roche, and compensation for travel expenses from Merck Serono. S.R.I. is a coapplicant and receives royalties on patent application WO/2010/046716 (U.K. patent no., PCT/GB2009/051441) entitled “Neurological Autoimmune Disorders.” The patent has been licensed for the development of assays for LGI1 and other VGKC complex antibodies. S.W., S.J., R.D., G.L., and S.M. have nothing to report. A.P. is a current employee of Janssen Inc. A.L.G. reports a patent for Method for High Percentage Recovery of Rare Cells (European application 18185007.4; US, Japan, and Chinese patents pending). J.M.G. received consulting fees from Biogen and Alexion, research support (to UCSF) from Genentech and previous research support to UCSF from Quest Diagnostics, service contract support (to UCSF) from MedDay, honoraria for editorial work from DynaMed Plus, and personal compensation for medical-legal consulting. M.D.G. reports grants and personal fees from Quest Diagnostics, Inc., grant support from the NIH, personal fees from Adept Field Consulting, Gerson Lehrman Group, Guidepoint Global, InThought, Best Doctors, Market Plus, and Advance Medical, speaker/teaching fees from the American Academy of Neurology Oakstone Publishing, and personal fees from medical-legal consulting. M.R.W. has received research support from Roche and Genentech. S.S.Z. is Deputy Editor of Neurology® Neuroimmunology & Neuroinflammation and is a member of the advisory board for the International Society of Neuroimmunology. He has served as a consultant and received honoraria from Biogen Idec, EMD Serono, Genzyme, Novartis, Roche/Genentech, and Teva Pharmaceuticals, Inc., and has served or serves on Data Safety Monitoring Boards for Lilly, BioMS, Teva, and Opexa Therapeutics. Currently, he receives research grant support from the NIH, the NMSS, the Maisin Foundation, Biogen, and Celgene. H.-C.v.B. is an employee of F. Hoffmann-La Roche, Basel, Switzerland. He has received compensation for consulting activities from Roche, Novartis, and Genzyme and research funding from Roche, Genentech, and Pfizer. Go to Neurology.org/NN for full disclosures. Acknowledgment The authors express their gratitude to the patients who agreed to participate in this research study. K.L.-H. received fellowship grants from the Deutsche Forschungsgemeinschaft (LE 3079/1-1) and the US National Multiple Sclerosis Society (NMSS) (FG 2067-A-1; G-1508-07064) and research support from the Munich Cluster for Systems Neurology (SyNergy), the Deutsche Forschungsgemeinschaft (SFB-TR-128), and the Hertie Foundation (MyLab program). S.R.I. is supported by the Wellcome (104079/Z/14/Z), BMA Research Grants-Vera Down Grant (2013) and Margaret Temple (2017), and by the Fulbright UK-US commission (MS-SOCIETY research AWARD). The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC; the views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health). A.L.G was supported by the NMSS Clinician-Scientist Development Award Kathleen C. Moore postdoctoral fellowship. M.D.G. was supported by the NIH, National Institute of Aging (R01 AG031189), and the Michael J. Homer Family Fund. Support was provided to S.S.Z. by the NIH (1 RO1 AI131624-01-A1; 1 R21 NS108150-01; 1 R21 AI142186-01), National Multiple Sclerosis Society (RG 1701-26628, RG 1807-31679 and RG 1801-29861), Maisin Foundation, and Guthy-Jackson Charitable Foundation. This study was supported by grants from the NIH/NINDS (K02NS072288 to H.-C.v.B., R01NS092835 initially to H.-C.v.B., transferred to Stephen L. Hauser). H.-C.v.B. was also supported by an endowment from the Rachleff Family Foundation. Appendix Authors Footnotes Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article. ↵* These authors contributed equally to the manuscript. The Article Processing Charge was funded by UCSF. Received September 5, 2019. Accepted in final form December 23, 2019. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. References 1.↵Irani SR, Michell AW, Lang B, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011;69:892–900.OpenUrlCrossRefPubMed 2.↵Thompson J, Bi M, Murchison AG, et al. The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain 2018;141:348–356.OpenUrlCrossRef 3.↵Ohkawa T, Fukata Y, Yamasaki M, et al. Autoantibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1-ADAM22 interaction and reduce synaptic AMPA receptors. J Neurosci 2013;33:18161–18174. 4.↵Petit-Pedrol M, Sell J, Planaguma J, et al. LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory. Brain 2018;141:3144–3159.OpenUrl 5.↵Finke C, Prüss H, Heine J, et al. Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies. JAMA Neurol 2017;74:50–59.OpenUrl 6.↵Irani SR, Stagg CJ, Schott JM, et al. Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype. Brain 2013;136:3151–3162.OpenUrlCrossRefPubMed 7.↵van Sonderen A, Thijs RD, Coenders EC, et al. Anti-LGI1 encephalitis: clinical syndrome and long-term follow-up. Neurology 2016;87:1449–1456.OpenUrl 8.↵Palanichamy A, Apeltsin L, Kuo TC, et al. Immunoglobulin class-switched B cells form an active immune axis between CNS and periphery in multiple sclerosis. Sci Transl Med 2014;6:248ra106. 9.↵Lehmann-Horn K, Wang SZ, Sagan SA, Zamvil SS, von Budingen HC. B cell repertoire expansion occurs in meningeal ectopic lymphoid tissue. JCI Insight 2016;1:e87234.OpenUrl 10.↵D'Angelo S, Glanville J, Ferrara F, et al. The antibody mining toolbox: an open source tool for the rapid analysis of antibody repertoires. MAbs 2014;6:160–172.OpenUrlCrossRefPubMed 11.↵Barak M, Zuckerman NS, Edelman H, Unger R, Mehr R. IgTree: creating immunoglobulin variable region gene lineage trees. J Immunol Methods 2008;338:67–74.OpenUrlCrossRefPubMed 12.↵Irani SR, Alexander S, Waters P, et al. Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. Brain 2010;133:2734–2748.OpenUrlCrossRefPubMed 13.↵von Büdingen HC, Kuo TC, Sirota M, et al. B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Invest 2012;122:4533–4543.OpenUrlCrossRefPubMed 14.↵Kowarik MC, Astling D, Gasperi C, et al. CNS Aquaporin-4-specific B cells connect with multiple B-cell compartments in neuromyelitis optica spectrum disorder. Ann Clin Transl Neurol 2017;4:369–380.OpenUrl 15.↵Kreye J, Wenke NK, Chayka M, et al. Human cerebrospinal fluid monoclonal N-methyl-D-aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis. Brain 2016;139:2641–2652.OpenUrlCrossRefPubMed 16.↵Gadoth A, Zekeridou A, Klein CJ, et al. Elevated LGI1-IgG CSF index predicts worse neurological outcome. Ann Clin Transl Neurol 2018;5:646–650.OpenUrl 17.↵Varley J, Taylor J, Irani SR. Autoantibody-mediated diseases of the CNS: structure, dysfunction and therapy. Neuropharmacology 2018;132:71–82.OpenUrl 18.↵Makuch M, Wilson R, Al-Diwani A, et al. N-methyl-D-aspartate receptor antibody production from germinal center reactions: therapeutic implications. Ann Neurol 2018;83:553–561.OpenUrl 19.↵Prüss H, Finke C, Höltje M, et al. N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol 2012;72:902–911.OpenUrlCrossRefPubMed 20.↵Irani SR, Gelfand JM, Bettcher BM, Singhal NS, Geschwind MD. Effect of rituximab in patients with leucine-rich, glioma-inactivated 1 antibody-associated encephalopathy. JAMA Neurol 2014;71:896–900.OpenUrl
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Complete cognitive recovery in a severe case of anti-N-methyl-d-aspartate receptor encephalitis treated with electroconvulsive therapy | BMJ Case Reports

Unexpected outcome (positive or negative) including adverse drug reactions Case report Complete cognitive recovery in a severe case of anti-N-methyl-d-aspartate receptor encephalitis treated with electroconvulsive therapy Cæcilie Leding1, Lisbet Marstrand2 and Anders Jorgensen1,3 Psychiatric Center Copenhagen, Rigshospitalet, Mental health services in the Capital Region of Denmark, Copenhagen, Denmark Department of Neurology, Rigshospitalet, Copenhagen, Denmark Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Correspondence to Dr Anders Jorgensen; anders.01.joergensen{at}regionh.dk Abstract Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis usually presents with prominent neuropsychiatric symptoms and many patients experience cognitive sequelae. Electroconvulsive therapy (ECT) has been suggested as a part of the treatment, particularly for catatonia, but concerns that ECT may worsen the cognitive function and long-term outcome may limit its use. We present a case of anti-NMDA receptor encephalitis with severe neuropsychiatric manifestations including refractory catatonia and behavioural change. A pre-ECT neuropsychological assessment revealed dysfunction in multiple cognitive domains in spite of intensive pharmacological treatment. Twenty days after the ninth and last ECT treatment, the patient underwent the same neuropsychological tests, which showed normalised test results within all cognitive domains and no need of rehabilitation. The case demonstrates that the use of ECT in anti-NMDA receptor encephalitis with severe pretreatment cognitive dysfunction can be associated with a highly favourable cognitive outcome. View Full Text Statistics from Altmetric.com View Full Text Footnotes Contributors CL wrote the first draft of the paper. LM cowrote the paper and performed the neuropsychological tests. AJ wrote the final version of the paper. All authors have contributed to and approved the final version of the paper. Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests None declared. Patient consent for publication Obtained. Provenance and peer review Not commissioned; externally peer reviewed. Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. Copyright information: © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ. Read the full text or download the PDF: Subscribe Log in
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Causes of Memory Loss in Elderly Persons | Dementia and Cognitive Impairment | JAMA | JAMA Network

Causes of Memory Loss in Elderly Persons | Dementia and Cognitive Impairment | JAMA | JAMA Network | AntiNMDA | Scoop.it
This JAMA Patient Page describes different possible causes of memory loss, including neurodegenerative dementias and other conditions that may be reversible or...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Aleena, Age 23, Maryland

Aleena, Age 23, Maryland | AntiNMDA | Scoop.it
Hey! I’m Aleena. I was working at a preschool at the time and was attending a community college. I was really struggling with depression and ... Read More
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Pediatric autoimmune encephalitis | Neurology Neuroimmunology & Neuroinflammation

Pediatric autoimmune encephalitis | Neurology Neuroimmunology & Neuroinflammation | AntiNMDA | Scoop.it
Abstract Objective The aims of this study were (1) to describe the incidence of autoimmune encephalitis (AIE) and acute disseminated encephalomyelitis (ADEM) in children, (2) to validate the currently used clinical criteria to diagnose AIE, and (3) to describe pitfalls in the diagnosis of pediatric autoimmune (AI) and inflammatory neurologic disorders. Methods This study cohort consists of 3 patient categories: (1) children with antibody-mediated AIE (n = 21), (2) children with ADEM (n = 32), and (3) children with suspicion of an AI etiology of their neurologic symptoms (n = 60). Baseline and follow-up clinical data were used to validate the current guideline to diagnose AIE. In addition, patient files and final diagnoses were reviewed. Results One-hundred three of the 113 included patients fulfilled the criteria of possible AIE. Twenty-one children had antibody-mediated AIE, of whom 19 had anti-N-methyl-D-aspartate receptor (NMDAR), 1 had anti–α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, and 1 had anti–leucine-rich glioma-inactivated protein 1 encephalitis. Finally, 34 children had ADEM, and 2 children had Hashimoto encephalopathy. Mean incidence rates were 1.54 children/million (95% CI 0.95–2.35) for antibody-mediated AIE and 2.49 children/million (95% CI 1.73–3.48) for ADEM. Of the other 48 children, treating physicians' diagnoses were reviewed. In 22% (n = 6) of children initially diagnosed as having an AI/inflammatory etiology (n = 27), no support for AI/inflammation was found. Conclusion Besides anti-NMDAR encephalitis and ADEM, other AIEs are rare in children. The current guideline to diagnose AIE is also useful in children. However, in children with nonspecific symptoms, it is important to review data critically, to perform complete workup, and to consult specialized neuroinflammatory centers. Glossary ADEM=acute disseminated encephalomyelitis; AE=autoimmune etiology; AI=autoimmune; AIE=autoimmune encephalitis; AMPAR=α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; CBA=cell-based assay; CHANCE=Children's Autoimmunity Related to Neuropsychiatric symptoms, Chorea and Epilepsy; FBDS=faciobrachial dystonic seizures; GAD65=glutamic acid decarboxylase 65; HSVE=herpes simplex virus encephalitis; IPMSSG=International Pediatric Multiple Sclerosis Study Group; ivMP=IV methylprednisolone; LGI1=leucine-rich glioma-inactivated protein 1; MOG=myelin oligodendrocyte glycoprotein; NMDA receptor=N-methyl-D-aspartate receptor; TPO=thyroid autoantibodies Autoimmune encephalitis (AIE) has expanded the already comprehensive list of pediatric neuroinflammatory disorders of the CNS. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and acute disseminated encephalomyelitis (ADEM) are the most frequently described cause of AIE in children,1,–,4 and disease courses have been studied in detail, including treatment responses, functional recovery,1,4 and long-term neuropsychological outcome.5 Next to anti-NMDAR, other neuronal antibodies have been described only sporadically in children,6,–,8 whereas in adults, reported incidence of these antibodies has increased dramatically.9,10 This could indicate that besides anti-NMDAR encephalitis, neuronal antibodies occur less frequent in children or that these syndromes are unrecognized. In 2016, Graus et al.11 have described criteria to diagnose antibody-mediated AIE, ADEM, and other related autoimmune (AI) encephalitides, including Bickerstaff brainstem encephalitis, Hashimoto encephalopathy, and autoantibody-negative (seronegative) AIE, in adults and in children. These criteria allow physicians to start first-line immunotherapy in patients with typical limbic encephalitis or probable anti-NMDAR encephalitis before definite antibody diagnosis. As already stated by the authors, the criteria should be used with caution in children because the differential diagnosis is more widespread. This prospective, observational, cohort study describes the incidence of pediatric antibody-mediated AIE and ADEM in the Netherlands since 2015. In addition, the diagnostic criteria of Graus et al.11 are validated using data of prospectively collected cohorts of children with AIE, ADEM, and children with neurologic symptoms and suspicion of an autoimmune etiology (AE). Finally, we describe pitfalls in the diagnosis of pediatric AI and inflammatory neurologic disorders. Methods Patients This study cohort contains data of 3 patient groups, included between January 2015 and December 2018 in the Netherlands. The first group consists of all Dutch children, aged 0–18 years, diagnosed with antibody-mediated (definite) AIE. Antibodies were detected in serum and CSF, using commercial cell-based assays (CBAs; Euroimmun, Lübeck, Germany). Antibodies were confirmed with immunohistochemistry. All children were included after diagnosis and are being followed prospectively since. The second group consists of all Dutch children with ADEM diagnosed according to the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria.12 who were prospectively included in the nationwide, multicenter PROUD kids study.13 The third group consists of children with a suspected AE of their neurologic symptoms. These children were prospectively included in the observational, multicenter, “Children's Autoimmunity Related to Neuropsychiatric symptoms, Chorea and Epilepsy” (CHANCE) study. The CHANCE study was a multicenter study, with national accrual, but no means to be complete. Inclusion criteria were age below 18 years at symptom onset and one of the following clinical phenotypes: (1) limbic encephalitis, (2) new-onset status epilepticus, (3) acute encephalopathy, or (4) neuropsychiatric symptoms combined with symptoms of basal ganglia dysfunction. All serum samples, and if available CSF samples, were screened for neuronal antibodies using immunohistochemistry14 and CBAs (Euroimmun, Lübeck, Germany). Questionable or positive samples were tested with conformational laboratory techniques, including live hippocampal neurons,15 in-house CBAs, and ELISA. Antithyroid autoantibodies (TPO) were detected by fluorescence enzyme immunoassay on the Phadia 250 system using EliA according to the manufacturer's instructions (Thermo Fisher Scientific, Freiburg, Germany). Data about medical history, disease course, treatment responses, and final diagnoses were collected. Data were collected from interviews with patients, from treating physicians, or were retrieved from patient files. Definitions The criteria of Graus et al.11 were used to define possible AIE, definite AI limbic encephalitis, probable anti-NMDAR encephalitis, Bickerstaff brainstem encephalitis, Hashimoto encephalopathy, and seronegative but probable AIE. The IPMSSG criteria12 were used to define ADEM. Final etiology was classified as (1) Definite AIE, including children with antibody-mediated AIE and ADEM. (2) Probable AIE, according to the diagnostic criteria.11 This category consisted of children with ADEM without follow-up MRI and of children with Hashimoto encephalopathy. (3) Possible AE/inflammatory, included children not fulfilling any of the diagnostic criteria panels, but with support for autoimmunity or inflammation. This category consisted partially of children with clinically defined acquired AE/inflammatory disorders, such as Rasmussen encephalitis or Sydenham chorea, and partially of children with MRI or CSF abnormalities pointing toward an AE/inflammatory etiology (pleocytosis, elevated protein, or oligoclonal bands in CSF, and MRI lesions in the temporal lobe), with exclusion of other causes, and not fulfilling the criteria of seronegative AIE.11 (4) Unknown etiology and no support for AE/inflammatory, including children without MRI or CSF abnormalities pointing toward and AE/inflammatory etiology. (5) Other diagnosis and no support for AE/inflammatory. R.F.N., M.J.T., and M.A.A.M.d.B. reviewed follow-up etiologies. Definite diagnoses were determined by consensus. Standard protocol approvals, registrations, and patient consents The Institutional Review Board of the Erasmus MC University Medical Center approved the study protocol (MEC- 2014-048; MEC-2005-247). Informed consent was obtained from all parents and additionally from children aged 12–17 years at inclusion. Statistics The annual incidence rate (from 2015 to 2018) was calculated with 95% CIs, assuming a Poisson distribution. Available data of the Dutch pediatric population were used (StatLine; statline.cbs.nl/statweb/). Comparisons were performed using the χ2 test or the Kruskal-Wallis test. Data availability Any data not published in this article are available at the Erasmus MC University Medical Center. Patient-related data will be shared on request from any qualified investigator, maintaining anonymization of the individual patients. Results Patient characteristics We included 113 patients. Twenty-one patients had definite AIE (19%), including 19 (90%) children with anti-NMDAR encephalitis. Among them, 12 had an idiopathic etiology (63%), 6 children recently had herpes simplex virus encephalitis (HSVE; 32%), and 1 girl had an ovarian teratoma (5%) detected shortly after disease onset. The other 2 children with neuronal antibodies had anti–leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis (n = 1; 5%) and anti–α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis (n = 1; 5%). Thirty-two children diagnosed with ADEM (28%) were included from the PROUD kids cohort. The other 60 patients (53%) were included from the CHANCE study. Incidence The annual incidence rates of antibody-mediated AIE and ADEM of 4 consecutive years (2015–2018) are shown in table 1. Mean incidence rates were 1.54 children/million (95% CI 0.95–2.35) and 2.49 children/million (95% CI 1.73–3.48) for AIE and ADEM, respectively. View inline View popup Table 1 Annual incidence of pediatric AIE and ADEM Validation of AIE criteria Of all 113 patients included, 103 (89%) fulfilled the criteria of possible AIE (figure 1). Demographical data are described in table 2. Children with AIE were more often female (p = 0.023), and children with ADEM were younger (p < 0.0001). Ten patients included in the CHANCE cohort did not fulfill the criteria and were excluded because of the absence of working memory deficits or psychiatric symptoms (n = 6) or because of the longer duration of symptoms (n = 4). These 10 children had epilepsy without additional symptoms (n = 4), psychiatric disorders (n = 3), mild encephalopathy with reversible lesion in the splenium (n = 1), Niemann-Pick disease type C (n = 1), or Rasmussen encephalitis without epilepsy (n = 1). Figure 1 Flowchart showing the validation of the diagnostic criteria of AIE aAccording to the International Pediatric Multiple Sclerosis Study Group criteria. bIn 21 of the 22 patients without new lesions on the second MRI anti–myelin oligodendrocyte glycoprotein (MOG) was tested; in 8/21, antibodies were present (38%). cIn 10 of the 12 patients who had no follow-up MRI, anti-MOG was tested, of them 40% (n = 4) tested positive. dOf whom, 8 had an idiopathic etiology, and 3 recently had herpes simplex virus encephalitis. In blue: probable diagnosis, first-line immunotherapy can be started. In green: definite diagnosis. ADEM = acute disseminated encephalomyelitis; AE = autoimmune etiology; AIE = autoimmune encephalitis; AMPAR = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; GQ1b = Ganglioside Q1b; LGI1 = leucine-rich glioma-inactivated protein 1; NMDAR = NMDA receptor; SN-AIE = seronegative autoimmune encephalitis. View inline View popup Table 2 Demographic data and comparisons between groups Of the 103 children shown in the flowchart, 1 child had definite limbic encephalitis according to the criteria (figure e-1, links.lww.com/NXI/A197). This was a 9-year old boy who presented with tonic-clonic seizures originating in the left temporal lobe, followed by refractory status epilepticus. He was treated with valproic acid, midazolam, and phenytoin. After status epilepticus, he developed faciobrachial dystonic seizures (FBDS)16 and hyperactive behavior. He was considered to have anti-LGI1 encephalitis, later confirmed in his serum and CSF. He was treated with IV methylprednisolone (ivMP). Because of ongoing FBDS, he was treated again with ivMP and additionally with mycophenolate mofetil, which led to seizure freedom and complete recovery. The brain MRI showed demyelinating features in 34 children (33%). In all these children, encephalopathy and other symptoms appeared reversible. In 22/34 children, the brain MRI was repeated, and in none of them, new lesions were visible. These children were diagnosed as having definite ADEM (22/103; 21%). In 31/34, myelin oligodendrocyte glycoprotein (MOG) antibodies were tested. Twelve of 31 (39%) ADEM children were MOG positive, 4 children had a relapsing disease course (ADEM-optic neuritis [N = 3], and multiphasic demyelinating encephalomyelitis [n = 1]). Fourteen of the 68 remaining patients fulfilled the criteria of probable anti-NMDAR encephalitis, of whom 11 had NMDAR antibodies, whereas the other 3 had no NMDAR antibodies (table 3). Of the children with anti-NDMAR encephalitis, 8 children had an idiopathic etiology and 3 children recently had HSVE. View inline View popup Table 3 Patients without NMDA receptor antibodies fulfilling the criteria “probable anti-NMDA receptor encephalitis” Nine additional patients had neuronal antibodies, without fulfilling the criteria of probable anti-NMDAR encephalitis. Eight turned out to have definite anti-NMDAR encephalitis, of which 4 with an idiopathic etiology (50%) but with less symptoms, 3 post-HSVE (38%), and 1 girl had an ovarian teratoma triggering the antibody production (13%). The other patient was a 17-year-old girl with anti–acetylcholine receptor-positive bulbar myasthenia gravis and a thymoma, which was surgically removed. She developed severe memory problems and mood changes within days, accompanied by clinical signs of polyneuropathy. Laboratory results showed AMPAR antibodies in her serum and CSF and an elevated anti-CV2 titer in serum (>12,800). She was treated with ivMP and IV immunoglobulins resolving both the encephalitis and polyneuropathy. No patient had Bickerstaff brainstem encephalitis. All remaining 48 children with possible AIE were tested for TPO antibodies. Six of 48 children had an increased anti-TPO titer, of whom 2 met the criteria for Hashimoto encephalopathy. One of the other 4 patients (table 4) had diabetes mellitus type 1 and co-occurrence of low-titer anti-glutamic acid decarboxylase 65 (anti-GAD65), considered clinically irrelevant. View inline View popup Table 4 Patients with increased anti-TPO not fulfilling the criteria of Hashimoto encephalopathy Follow-up etiology of patients with possible AIE Nine of the 46 children (20%) were diagnosed by their treating physician with seronegative or probable AIE, whereas none of these children fulfilled the criteria of seronegative AIE. Four of these 9 children had a pleocytosis in CSF, but no MRI abnormalities in the mesial temporal lobe. In the other 5 children, brain MRI and white blood cell count in CSF were normal. However, complete CSF analysis, including immunoglobulin G (IgG) index and oligoclonal bands, was not performed. Concerning follow-up etiology based on treating physicians' diagnosis, these 46 children had (1) a possible AE/inflammatory etiology (n = 27), (2) no support for AE/inflammatory and another etiology (n = 9), and (3) no support for AIE/inflammatory and unknown etiology (n = 10). After revising the data, in 6 children (22%) initially considered as possible AE/inflammatory, no support for an AI/inflammatory etiology was found. Differential diagnosis of possible AIE In table 5, exemplary cases of the included patients with AIE and with other diagnoses are shown. These cases show overlapping features, which may suggest AIE, but also signs and symptoms pointing toward another diagnosis. View inline View popup Table 5 Mimics of autoimmune encephalitis in children27 Discussion This prospective observational cohort study shows that besides anti-NMDAR encephalitis and ADEM, the prevalence of other AI encephalitides is very low in children. Furthermore, we describe that these AI disorders show a stable incidence over the past 4 years. In addition, this study validates the criteria currently used to diagnose AIE and shows their usefulness to detect pediatric antibody-mediated AIE, ADEM, and Hashimoto encephalopathy in an early stage. In our cohort, a substantial number of children were diagnosed and treated as having an AI/inflammatory etiology of their neurologic symptoms, whereas in more than 20% of them, the support for autoimmunity or inflammation was lacking. The vast majority of children with definite AIE described in this cohort had anti-NMDAR encephalitis, whereas only 2 children had other neuronal antibodies (anti-LGI1 and anti-AMPAR). These antibodies have been described only sporadically in pediatric cases,17 next to other neuronal antibodies, including anti-gamma-aminobutyric acid B receptor,7 anti-gamma-aminobutyric acid A receptor,6 anti-glycine receptor,18 and anti-GAD65.19 The high prevalence of anti-NMDAR encephalitis in children compared with the very low prevalence of other antibodies is largely explained by epidemiologic factors. In our cohort, in more than 40% of the children with anti-NMDAR encephalitis, antibody production was triggered by HSVE or an ovarian teratoma, both occurring more in children and young adults.1,20 The other antibody-mediated AIE syndromes are not associated with these factors and are usually idiopathic or associated with malignancy, not occurring in childhood.11 No additional neuronal antibodies were identified in our prospectively collected cohort of children with possible AIE (CHANCE cohort), whereas others identified neuronal antibodies in 4%–10% of children with selected neurologic symptoms or syndromes (i.e., epilepsy21 and demyelinating disorders22). However, pathogenicity of most of the detected antibodies in these studies is unproven, including double-negative voltage-gated potassium channel antibodies (anti-voltage-gated potassium channel, without anti-LGI1 or anti-contactin-associated protein 2) and low-titer anti-GAD65.23,–,25 We describe that the current guideline to diagnose AIE is of additional value to correctly diagnose AI-related neurologic conditions in children. One of the most important panels in the current guideline is “probable anti-NMDAR encephalitis.” If children fulfill these criteria, immunotherapy can be started before definite antibody diagnosis. In our cohort, almost 70% of children with anti-NMDAR encephalitis with an idiopathic etiology could be identified by the use of these criteria, whereas 50% of post-HSVE anti-NMDAR encephalitis children fulfilled the criteria of “probable anti-NMDAR encephalitis.” As the criteria were meant to identify patients for initiation of treatment before antibody results are available, the identification of 70% of idiopathic patients is relevant and important. The criteria are less important in post-HSVE anti-NMDAR encephalitis. In most children with recent history of HSVE, deterioration of symptoms promptly leads to NMDAR antibodies testing because of increased knowledge of this syndrome.20 One-third of children with idiopathic or paraneoplastic anti-NMDAR encephalitis did not fulfill the criteria of probable anti-NMDAR encephalitis; these children had less symptoms, and most of them had milder disease courses than the ones who did fulfill the criteria. These findings emphasize the importance of also considering this disease in children with unexplained neuropsychiatric disorders without many additional signs. An important difficulty broached in this study was that in one-fifth of the children diagnosed with an AI or inflammatory etiology, no support for autoimmunity or inflammation was found. In many of these children, improvement after immunotherapy was considered as a criterion favoring autoimmunity. An unjustified conclusion, because many diseases can (temporarily) respond to immunotherapy, or the observed response may even be the natural course of the disease.26 However, there will always be a small level of uncertainty, which makes it even more important to perform complete workup in these children, MRI and CSF analysis, including IgG index and oligoclonal bands. In the diagnosis of these syndromes, it is important to look for signs and symptoms favoring autoimmunity or inflammation, but the differential diagnosis of possible AIE is broad, and other causes should also be considered, especially in children with aspecific signs. This study was limited because of the number of patients included. However, it is the first nationwide study describing annual incidence of pediatric antibody-mediated AIE. In the CHANCE cohort, coverage was well, but there was no nationwide coverage, and children may have been selected toward an AE, as samples of patients with a higher suspicion for AE are often referred to our center for antibody testing. Another limitation is that in most patients, CSF analysis was incomplete, and oligoclonal bands and IgG index were often lacking. Occasionally, this resulted in difficulties to adequately revise diagnosis. In doubt, we preferred to be cautious by diagnosing children with an AI of inflammatory disorder because of the therapeutic and prognostic implications. From this study, we can conclude that AIE seems to be recognized properly in children. The majority of children have anti-NMDAR encephalitis or ADEM whereas other AIE syndromes occur only sporadically in children. The current guideline to diagnose AIE syndromes seems to be a useful tool to detect children with an AE of neurologic symptoms. However, especially in children not fulfilling any of the current guideline panels, it is important to be critical before diagnosing them as having an AI or inflammatory etiology of their neurologic symptoms. In addition, it is essential to perform complete diagnostic workup and to consult specialized AI/inflammatory tertiary centers if in doubt. Study funding M.J.T. was supported by an Erasmus MC fellowship, has received funding from the Netherlands Organization for Scientific Research (NWO, Veni incentive), from the Dutch Epilepsy Foundation (NEF, project 14–19), and from ZonMw (Memorabel program). Disclosure M.A.A.M. de Bruijn, A.L. Bruijstens, A.E.M. Bastiaansen, A. van Sonderen, and M.W.J. Schreurs report no disclosures. P.A.E. Sillevis Smitt holds a patent for the detection of anti-DNER and received research support from Euroimmun. R.F. Neuteboom and R.D. Thijs report no disclosures. M.J. Titulaer received research funds for serving on a scientific advisory board of MedImmune LLC., and a travel grant for lecturing in India from Sun Pharma, India. M.J. Titulaer has filed a patent for methods for typing neurological disorders and cancer, and devices for use therein, and has received research funds for serving on a scientific advisory board of MedImmune LLC, for consultation at Guidepoint Global LLC, and an unrestricted research grant from Euroimmun AG. Go to Neurology.org/NN for full disclosures. Acknowledgment This work is generated within the European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases. Rogier Q. Hintzen: Deceased May 15, 2019. Appendix 1 Authors Appendix 2 CHANCE study group Footnotes Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article. The Article Processing Charge was funded by Erasmus University. Received December 2, 2019. Accepted in final form January 3, 2020. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. References 1.↵Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12:157–165.OpenUrlCrossRefPubMed 2.↵Armangue T, Titulaer MJ, Malaga I, et al. Pediatric anti-N-methyl-D-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients. J Pediatr 2013;162:850–856.e2.OpenUrlCrossRefPubMed 3.↵Florance NR, Davis RL, Lam C, et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009;66:11–18.OpenUrlCrossRefPubMed 4.↵de Mol CL, Wong YYM, van Pelt ED, et al. Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study. J Neurol 2018;265:1310–1319.OpenUrl 5.↵de Bruijn M, van Sonderen A, van Coevorden-Hameete MH, et al. Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABABR encephalitis. Neurology 2019;92:e2185–e2196.OpenUrl 6.↵Petit-Pedrol M, Armangue T, Peng X, et al. Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies. Lancet Neurol 2014;13:276–286.OpenUrlCrossRefPubMed 7.↵Kruer MC, Hoeftberger R, Lim KY, et al. Aggressive course in encephalitis with opsoclonus, ataxia, chorea, and seizures: the first pediatric case of gamma-aminobutyric acid type B receptor autoimmunity. JAMA Neurol 2014;71:620–623.OpenUrl 8.↵Hacohen Y, Singh R, Rossi M, et al. Clinical relevance of voltage-gated potassium channel–complex antibodies in children. Neurology 2015;85:967–975.OpenUrlCrossRefPubMed 9.↵van Sonderen A, Thijs RD, Coenders EC, et al. Anti-LGI1 encephalitis: clinical syndrome and long-term follow-up. Neurology 2016;87:1449–1456.OpenUrl 10.↵van Coevorden-Hameete MH, de Bruijn M, de Graaff E, et al. The expanded clinical spectrum of anti-GABABR encephalitis and added value of KCTD16 autoantibodies. Brain 2019;142:1631–1643.OpenUrl 11.↵Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404.OpenUrlCrossRefPubMed 12.↵Krupp LB, Tardieu M, Amato MP, et al. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler 2013;19:1261–1267.OpenUrlCrossRefPubMed 13.↵Ketelslegers IA, Catsman-Berrevoets CE, Neuteboom RF, et al. Incidence of acquired demyelinating syndromes of the CNS in Dutch children: a nationwide study. J Neurol 2012;259:1929–1935.OpenUrlCrossRefPubMed 14.↵Ances BM, Vitaliani R, Taylor RA, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain 2005;128:1764–1777.OpenUrlCrossRefPubMed 15.↵Gresa-Arribas N, Titulaer MJ, Torrents A, et al. Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol 2014;13:167–177.OpenUrlCrossRefPubMed 16.↵Irani SR, Michell AW, Lang B, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011;69:892–900.OpenUrlCrossRefPubMed 17.↵Lopez-Chiriboga AS, Klein C, Zekeridou A, et al. LGI1 and CASPR2 neurological autoimmunity in children. Ann Neurol 2018;84:473–480.OpenUrl 18.↵Hacohen Y, Wright S, Waters P, et al. Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry 2013;84:748–755. 19.↵Mishra N, Rodan LH, Nita DA, Gresa-Arribas N, Kobayashi J, Benseler SM. Anti-glutamic acid decarboxylase antibody associated limbic encephalitis in a child: expanding the spectrum of pediatric inflammatory brain diseases. J Child Neurol 2014;29:677–683.OpenUrlCrossRefPubMed 20.↵Armangue T, Spatola M, Vlagea A, et al. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol 2018;17:760–772.OpenUrlCrossRef 21.↵Borusiak P, Bettendorf U, Wiegand G, et al. Autoantibodies to neuronal antigens in children with focal epilepsy and no prima facie signs of encephalitis. Eur J Paediatr Neurol 2016;20:573–579.OpenUrl 22.↵Kiztanir H, Bektas G, Yildiz EP, et al. Coexisting neuronal autoantibodies among children with demyelinating syndromes. Brain Dev 2017;39:248–251.OpenUrl 23.↵Lang B, Makuch M, Moloney T, et al. Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies. J Neurol Neurosurg Psychiatry 2017;88:353–361. 24.↵van Sonderen A, Schreurs MW, de Bruijn MA, et al. The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies. Neurology 2016;86:1692–1699.OpenUrlCrossRefPubMed 25.↵Muñoz-Lopetegi A, de Bruijn M, Boukhrissi S, et al. Neurologic syndromes related to anti-GAD65: Clinical and serological response to treatment. Neurol Neuroimmunol Neuroinflamm 2020;7:e696. doi: 10.1212/NXI.0000000000000696.OpenUrl 26.↵Bakker DP, Catsman-Berrevoets CE, Neuteboom RF. Effectiveness of a hybrid corticosteroid treatment regimen on refractory childhood seizures and a review of other corticosteroid treatments. Eur J Paediatr Neurol 2015;19:553–560.OpenUrl 27.↵Armangue T, Petit-Pedrol M, Dalmau J. Autoimmune encephalitis in children. J Child Neurol 2012;27:1460–1469.OpenUrlCrossRefPubMed
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Woman, 30, was misdiagnosed with schizophrenia after rare immune disease triggered hallucinations – Brinkwire

Woman, 30, was misdiagnosed with schizophrenia after rare immune disease triggered hallucinations – Brinkwire | AntiNMDA | Scoop.it
A woman who hallucinated the Mexican Cartel were hunting her was misdiagnosed with schizophrenia before doctors realised she had a rare and deadly immune disease.  Samantha Redfield, of Angels Camp, California, suddenly began experiencing strange symptoms over a two week period in October 2019. She was rushed to hospital when she suffered a seizure, and over the next few days, began to hallucinate her sisters were dead and sob uncontrollably. When brain scans and blood tests showed nothing was wrong, 30-year-old Mrs Redfield was referred to a psychiatrist with suspected schizophrenia, by which point she hadn’t slept for ten days.   But the psychiatrist said there was something more sinister going on. She told Mrs Redfield’s family to take her straight back to A&E. After taking fluid from Mrs Redfield’s spine, the doctors were able to diagnose autoimmune encephalitis, which causes the body’s immune system to attack healthy brain cells. Inflammation and swelling lead to symptoms similar to psychosis.  Mrs Redfield was kept in hospital for two weeks while having treatment which filters the blood and removes harmful antibodies. She has almost fully recovered. Speaking about her hallucinations, Mrs Redfield said: ‘The hallucinations that I do somewhat remember were thinking I lost loved ones, I remember sobbing thinking two of my sisters had died.  ‘I also remember bits and pieces of being incredibly scared that the Mexican Cartel was hunting me, that they were outside our home. I remember very little. ‘There is what I believe a good two weeks where I remember nothing. I would be extremely happy one moment and a wreck the next.  ‘I had trouble speaking, I couldn’t write or read. I was told I stayed awake for ten days straight. ‘To simply put it, my body was attacking my brain and my body was fighting for its life.’  Mrs Redfield suddenly started to experience symptoms of stiffness and numbness in her right hand in October 2019. Over two weeks, the numbness Mrs Redfield was feeling spread to her upper right lip and she struggled to feed herself with a fork without dropping it. She said: ‘I knew something was wrong, I quickly became anxious and worried. These symptoms came on quickly over a two-week period just prior to my first seizure. ‘I remember being at a restaurant with my dad and telling him to watch this – I could feel when my hand was about to seize up – I picked up the fork with food on it and before I brought it to my mouth, my hand gave away, dropping the fork and food hit the table, we weren’t sure what to think. ‘These symptoms continued to escalate and a week after the fork incident I had my seizure.  ‘We would eventually find out these symptoms on the right side of my body were caused by swelling in the left side of my brain.’  Mrs Redfield was rushed to A&E on October 25 following her first seizure, when she also broke her ankle. A doctor ordered blood tests and MRI scans, which all came back clear.  ‘To have them come back clear was honestly scary as it left us with no answers as to what had caused the seizure,’ Mrs Redfield said. ‘Unfortunately, the days following with additional MRIs, EEGs and blood work were a blur. My health quickly started to deteriorate and do not remember much or if any of these tests.’ After being discharged from the hospital and given the all clear, Mrs Redfield can’t fully remember what happened to her as her health rapidly declined. From speaking to her family and her husband, Codey, 40, Mrs Redfield knew that she started to hallucinate. She believed that her two sisters, Katie, 29, and Danielle, 20, had died and that the Mexican Cartel were hunting her and waiting outside her house. On November 5, Mrs Redfield’s family took her back to the neurologist who misdiagnosed her with schizophrenia. Mrs Redfield said: ‘My dad scheduled an appointment with a psychiatrist the very next day. ‘I’ve been told the psychiatrist said that this is not schizophrenia, she understood I was a healthy happy 29-year-old only weeks before, she knew something was wrong.  ‘She recommended my family get me to an emergency room immediately to get admitted. My parents did just that.’  Mrs Redfield was in hospital for two weeks during which time countless tests and a spinal tap diagnosed autoimmune encephalitis.  Every years there are up to 6,000 cases of encephalitis of all types in the UK, and approximately 25,000 in the US, according to Encephalitis Society.  The condition causes inflammation of the brain and can cause traumatic symptoms similar to those seen in patients with psychosis, including confusion, hallucinations or strange behaviour. Viruses are the most common cause of infectious encephalitis. Mrs Redfield was diagnosed with a rarer autoimmune type.  It’s caused by a problem with the immune system, but doctors are still baffled as to why the body behaves this way. Mrs Redfield underwent plasma treatment called plasmapheresis which finally brought her out of her psychosis-like state. She was discharged from hospital on November 22.  She said: ‘This psychiatrist is the reason we ended up admitted at UC Davis Medical Centre where my life would be saved.  ‘The doctors turned to an aggressive treatment of plasma exchanges that truly saved my life and brought me out of psychosis.  ‘They inserted a catheter near my collar bone. Every other day a specialist would come in with a machine and bottles of plasma. This machine would take my blood into the machine where it would separate my plasma from my red blood cells. ‘The machine would then mix my plasma with the fresh plasma and inject it back into my body.  ‘This was a two-hour process that happened every other day, five times. By the second or third treatment I started to come out of my state of psychosis.’ Mrs Redfield is about to undergo immunoglobulin therapy (IVIg), whereby a mixture of antibodies are injected into the blood to help the body fight disease. She will have IVIg once a month for the next six months to a year to prevent the 20 to 30 per cent chance of relapse.  In the meantime, Mrs Redfield must take it easy; she’s put her career in marketing on hold while she gets better due to her limited energy and hasn’t had a seizure since she was in hospital. Mrs Redfield is still in recovery from her terrifying ordeal but wants to spread the word and raise awareness of her condition. She said: ‘In my case, my antibodies were not working correctly, and they turned on my body and attacked the NMDA receptors in my brain.  ‘NMDA receptors are responsible for a lot of our daily activity like human interaction, our memories, judgement and so much more.  ‘Each day is better. My body allows me about four hours of energy a day so the things I do each day are limited still. ‘I can’t drive due to the seizures and with little energy am unable to work so a lot of my time is spent with friends and family or binge watching my favourite shows. I still have a long road ahead of healing and have to remind myself daily to take it easy.  ‘My new neurologist says there is a twenty to thirty per cent chance of relapse, but we are hopeful IVIG will lessen those chances.’ Mrs Redfield added: ‘I am so thankful for the ability to share my story and raise awareness through it, in hopes of saving a life – many are misdiagnosed, not treated and trapped in their own bodies and mental health hospitals. ‘Take care of yourself, be gentle with yourself, don’t apologise for something that’s out of your control. You can’t rush healing.’ For more information, visit Mrs Redfield’s Instagram.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

NMDA receptor antibodies in autoimmune encephalopathy alter oligodendrocyte function. - PubMed - NCBI

NMDA receptor antibodies in autoimmune encephalopathy alter oligodendrocyte function. - PubMed - NCBI | AntiNMDA | Scoop.it
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Autoimmune Encephalitis and Epilepsy: Evolving Definition and Clinical Spectrum | Read by QxMD

Autoimmune Encephalitis and Epilepsy: Evolving Definition and Clinical Spectrum | Read by QxMD | AntiNMDA | Scoop.it
JOURNAL ARTICLE Autoimmune Encephalitis and Epilepsy: Evolving Definition and Clinical Spectrum Joo Hee Seo, Yun-Jin Lee, Ki Hyeong Lee, Elakkat Gireesh, Holly Skinner, Michael Westerveld Clinical and experimental pediatrics 2020 February 6 Advances in autoimmune encephalitis studies in the past 10 years have headed to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to the disorder. The disorder or syndrome has been linked to a wide variety of pathologic processes associated with the neural-specific autoantibodies targeting both intracellular and plasma membrane antigens. However, current criteria for autoimmune encephalitis are very dependent on antibody testing and response to immunotherapy, which might delay the diagnosis. This form of encephalitis can involve children with multifaceted presentation of seizures and unexpected behavioral changes. The spectrum of neuropsychiatric symptoms in children is less definitive than in adults, and the incorporation of clinical, immunological, electrophysiological and neuroradiological results is critical for a diagnostic approach. In this review, we document the most appropriate data both clinical and immunologic characteristics of the autoimmune encephalitis known so far, with the goals of assisting clinicians in the differential diagnosis and providing a promptly effective treatment. Read this article (multiple options) Discussion You are not logged in. Sign Up or Log In to join the discussion. Related Papers Autoimmune Encephalitis and Epilepsy: Evolving Definition and Clinical Spectrum. Joo Hee Seo, Yun-Jin Lee, Ki Hyeong Lee, Elakkat Gireesh, Holly Skinner, Michael Westerveld Korean Journal of Pediatrics 2019 August 16 An evolving redefinition of autoimmune encephalitis. Susanna Esposito, Nicola Principi, Paolo Calabresi, Donato Rigante Autoimmunity Reviews 2019, 18 (2): 155-163 Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren's syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor's expression, impair glutamate-induced signaling and function, activate blood brain barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by immunotherapy. Mia Levite Journal of Neural Transmission 2014, 121 (8): 1029-75 A clinical approach to diagnosis of autoimmune encephalitis. Francesc Graus, Maarten J Titulaer, Ramani Balu, Susanne Benseler, Christian G Bien, Tania Cellucci, Irene Cortese, Russell C Dale, Jeffrey M Gelfand, Michael Geschwind, Carol A Glaser, Jerome Honnorat, Romana Höftberger, Takahiro Iizuka, Sarosh R Irani, Eric Lancaster, Frank Leypoldt, Harald Prüss, Alexander Rae-Grant, Markus Reindl, Myrna R Rosenfeld, Kevin Rostásy, Albert Saiz, Arun Venkatesan, Angela Vincent, Klaus-Peter Wandinger, Patrick Waters, Josep Dalmau Lancet Neurology 2016, 15 (4): 391-404 Autoimmune epilepsy in children: case series and proposed guidelines for identification. Jehan Suleiman, Fabienne Brilot, Bethan Lang, Angela Vincent, Russell C Dale Epilepsia 2013, 54 (6): 1036-45 Autoimmune Epilepsy. Michel Toledano, Sean J Pittock Seminars in Neurology 2015, 35 (3): 245-58 Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis. Marianna Spatola, Josep Dalmau Current Opinion in Neurology 2017, 30 (3): 345-353 [Recent progress in autoimmune encephalitis and its related disorders]. Takahiro Iizuka Rinshō Shinkeigaku, Clinical Neurology 2019 August 29, 59 (8): 491-501 [Autoimmune encephalitis, clinical, radiological and immunological data]. J Aupy, N Collongues, F Blanc, C Tranchant, E Hirsch, J De Seze Revue Neurologique 2013, 169 (2): 142-53 Autoimmune encephalitis: recent updates and emerging challenges. Sudarshini Ramanathan, Shekeeb S Mohammad, Fabienne Brilot, Russell C Dale Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia 2014, 21 (5): 722-30
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

'Milestone' Discovery Offers Hope for Life-Threatening Disorders

'Milestone' Discovery Offers Hope for Life-Threatening Disorders | AntiNMDA | Scoop.it
The discovery that an antibody is linked to a wider range of autoimmune diseases than previously thought offers new hope for children with life-threatening neurologic disorders.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Breaking boundaries between demyelinating disorders and autoimmune encephalitis

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated syndromes are now considered a distinct and new entity in the field of CNS inflammatory demyelinating disorders, different from multiple sclerosis and aquaporin4-IgG-positive neuromyelitis optica.1 MOG antibody-associated syndromes are...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study

Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study | AntiNMDA | Scoop.it
The spectrum of paediatric MOG antibody-associated syndromes is wider than previously
reported and includes demyelinating syndromes and encephalitis. Recognition of these
disorders has important clinical and prognostic implications.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Cerebral functional activity and connectivity changes in anti-N-methyl-D-aspartate receptor encephalitis: A resting-state fMRI study. - PubMed - NCBI

Cerebral functional activity and connectivity changes in anti-N-methyl-D-aspartate receptor encephalitis: A resting-state fMRI study. - PubMed - NCBI | AntiNMDA | Scoop.it
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Young woman ends up on psych ward after symptoms mistaken for breakdown - Mirror Online

Young woman ends up on psych ward after symptoms mistaken for breakdown - Mirror Online | AntiNMDA | Scoop.it
University student Lucy Dawson was in the ward for about four months before she was eventually diagnosed with a medical condition called anti-NMDA receptor encephalitis...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis | NEJM

Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis | NEJM | AntiNMDA | Scoop.it
Abstract Background Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test. Methods In a 1-year, multice...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

My "Finger Twitch" Turned out to Be Brain Inflammation

My "Finger Twitch" Turned out to Be Brain Inflammation | AntiNMDA | Scoop.it
Young and healthy, this woman suddenly was suffering hallucinations and seizures; her brain was under attack from her own body.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

The story of how I went from being a healthy, 20 year old at university, to being incorrectly locked in a mental ward for 3 months and became permanently disabled at 21.

The story of how I went from being a healthy, 20 year old at university, to being incorrectly locked in a mental ward for 3 months and became permanently disabled at 21. | AntiNMDA | Scoop.it
In October 2016, I had just begun my third and final year of university, happily planning my Halloween costume with my housemates, attending freshers’ events and lectures, when suddenly and unexpectedly, my whole life changed forever.
No comment yet.