Postinfectious Encephalitis Research Articles

The Spectrum Between Catatonia and Functional Neurologic Disorder Superimposed on Post-Infectious Encephalitis in a Marine Recruit.

Catatonia, a neuropsychiatric condition characterized by abnormal speech, volition, and movement, is primarily thought of as a symptom of a primary psychiatric pathology, but there are a variety of non-psychiatric medical conditions that must be considered. As a result of symptomatic complexity and the wide range of differential diagnoses, catatonia-like symptoms can cloud the clinical evaluation and complicate treatment regimens. Within the realm of catatonic-like diagnoses is functional neurological disorder because of its vast range of potential presentations. Functional neurologic disorder can be diagnosed by evidence of incompatibility between neurologic symptoms and recognized neurological or medical conditions. Clinical uncertainty is further intensified in the presence of co-morbid medical etiologies because of inability to neatly delegate symptoms to a specific diagnosis. The blurred spectrum between catatonia and functional neurologic disorder is highlighted in this patient's complex clinical presentation while being further obscured in the setting of a possible overlying encephalitis exacerbating the presentation. This case report presents a unique case of a Marine recruit whose inconsistent catatonic symptoms caused diagnostic uncertainty and were ultimately decided to have neurologic and psychiatric contributions, highlighting that diagnoses are not mutually exclusive and should be continually re-assessed as new data become available. This report also showcases the distinctiveness of U.S. Marine culture and possible physical manifestations because of imposed psychological stress.

A man who changed six spectacles: а case of Heidenhain variant of the Creutzfeldt–Jakob disease

Creutzfeldt–Jakob Disease (CJD) is a rare and rapidly progressive condition. A 54-year-old professor initially presented with insidious, progressive visual symptoms. Imaging suggested post-infectious encephalitis, but symptoms progressed to ataxia, coordination difficulties, and cognitive decline. Repeat MRI revealed findings consistent with CJD, supported by clinical and electrophysiological evidence. Though 14-3-3 protein in CSF was inconclusive, Heidenhain variant CJD was strongly suspected. Isolated visual symptoms progressing rapidly alongside ataxia and dementia prompt suspicion of this variant. Clinical examination, neuroimaging, and EEG play crucial roles in the diagnosis.

Correction of dosage of the drug: Post-infectious basal ganglia encephalitis and axonal variant of Guillain-Barré syndrome after COVID-19 infection: an atypical case report

Correction of dosage of the drug: Post-infectious basal ganglia encephalitis and axonal variant of Guillain-Barré syndrome after COVID-19 infection: an atypical case report

Case Series of Patients with Brainstem Inflammation Causing Paroxysmal Movement Disorders (P4-5.016)

<h3>Objective:</h3> We describe five patients with various neuroinflammatory diseases who developed Paroxysmal Movement Disorders (PMD). <h3>Background:</h3> PMD are a rare phenomenon that has been described in patients with multiple sclerosis since the 1940s. PMD are typically responsive to carbamazepine. One subtype of PMD is paroxysmal dysarthria and ataxia syndrome (PDA), characterized by stereotyped episodes of dysarthria and ataxia, lasting seconds and recurring several times per day. This is thought to be due to transverse ephaptic transmission between demyelinated axons in the brainstem. Recently, cases of PDA in other neuroinflammatory diseases such as Behcet’s disease, MOG-antibody disease (MOGAD), Bickerstaff encephalitis, and anti-NMDA encephalitis have been described but the spectrum of PMD in neuroinflammatory diseases has not been sufficiently studied. <h3>Design/Methods:</h3> Case report series. <h3>Results:</h3> We describe in detail five patients with CNS inflammatory diseases who developed PMD. Underlying diseases were chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), MS, MOGAD, and post-infectious encephalitis (COVID and LaCrosse virus). Four patients developed PDA, while one presented with paroxysmal esophageal contractions. Paroxysms were brief (less than 10 seconds) and frequent (up to hundreds of times a day). On MRI, four patients had lesions in the medial midbrain and one had a lesion in a cerebellar peduncle. In four cases paroxysms were treated successfully with carbamazepine. All patients had complete or near-complete remission of their PMD. <h3>Conclusions:</h3> This series highlights that different neuroinflammatory disorders can cause PMD. This is the first report of PDA in CLIPPERS or post-COVID encephalitis, and the second report in MOGAD. Most patients had lesions in the dorsal midbrain below the red nucleus, a site commonly reported to cause PDA. Treatment with carbamazepine was successful. PMD in neuroinflammatory disease is important to recognize as symptoms can be debilitating but successfully treated. This case series can help improve awareness of this rare condition. <b>Disclosure:</b> Dr. Luxenberg has nothing to disclose. The institution of Dr. Wang has received research support from Genentech. The institution of Dr. Wundes has received research support from Benaroya Research Institute . The institution of Dr. Von Geldern has received research support from Novartis. The institution of Dr. Von Geldern has received research support from National MS Society. Dr. Von Geldern has received personal compensation in the range of $0-$499 for serving as a DSMB member with NIH, NINDS. Dr. Von Geldern has a non-compensated relationship as a editorial board member with MS and Related Disorders Journal that is relevant to AAN interests or activities.

Wernicke’s Encephalopathy Preceded by COVID-19 Infection: A Case Report (P2-7.006)

<h3>Objective:</h3> To describe a case of post-infectious encephalopathy following COVID-19 with MRI brain changes suggestive of Wernicke’s encephalopathy and a transient presence of anti-GAD65 autoantibodies in the cerebrospinal fluid (CSF). <h3>Background:</h3> Chronic malnutrition and alcoholism are known risk factors for developing Wernicke’s encephalopathy. However, it is not typically associated with thiamine deficiency resulting from acute starvation as in this case of severe respiratory syndrome due to coronavirus-2 (SARS-CoV-2). <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 59 year-old female presented to the neurointensive care unit with subacute disorientation, decreased verbal fluency, memory deficits, gait dysfunction, confusion, and rapid weight loss that progressed to coma over two months following COVID-19 infection. Initial lumbar puncture (LP) one month following infection was notable for positive anti-GAD65 autoantibodies and elevated protein which was suggestive of post-infectious encephalitis. MRI brain at the time of initial evaluation was unremarkable for abnormalities and the patient’s symptoms continued to progress to include depressed mentation. Subsequent MRIs of the brain with and without contrast showed T2 FLAIR abnormalities in the periaqueductal grey, lateral walls of the third ventricle, splenium, and mammillary bodies. Repeat LP showed similar CSF profile and absence of anti-GAD65 autoantibodies. Electroencephalogram showed slowing with frequent generalized periodic discharges. Patient’s treatment course included high dose thiamine, methylprednisolone, intravenous immunoglobulin, and plasmapheresis without clinical improvement. The patient did not show meaningful cognitive recovery and was transitioned to comfort care. <h3>Conclusions:</h3> The patient’s progression to coma was suspected to be due to development of COVID-19 encephalopathy precipitating Wernicke’s encephalopathy in the setting of severely diminished oral intake. Because Wernicke’s encephalopathy is potentially reversible with thiamine administration, we propose that early empiric treatment should be considered in all patients suffering from persistent encephalopathy following COVID-19 infection. <b>Disclosure:</b> Dr. Volski has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Chakrabarti Pulakanti has nothing to disclose. Dr. Dolla has nothing to disclose.

A Sharp Rise in Autoimmune Encephalitis in the COVID-19 Era: A Case Series.

Autoimmune encephalitis was very rare prior to the current pandemic. A sharp rise in cases has been observed from March to August of 2022 in Los Angeles. Such an increase, especially with certain types of antibodies, may point toward the possibility of post-infectious autoimmune encephalitis. While review articles on autoimmune encephalitisduring this pandemic have been published, a sharp rise in one geographic area within a short period of time has not been documentedyet. To report an alarming increase in autoimmune encephalitis with mostly positive glutamic acid decarboxylase (GAD) and/or voltage-gated potassium channel (VGKC) antibodies over six months during 2022 in Downtown Los Angeles. This is an observational case series from one neurocritical care practice in Downtown Los Angeles. Autoimmune encephalitis antibody panels were sent to patients with altered mental status or neurologic deficits of unclear etiology from March to August of 2022. Of the 29 patients tested, 12 reports came back positive. Ten had positive GAD and/or VGKC antibodies, one had a positive myelin oligodendrocyte glycoprotein antibody, and one had a positive leucine-richglioma-inactivated 1 protein antibody; a 41% positive rate. This observation has important implications: (1) We may be entering an era of heightened autoimmune encephalitis. (2) These occurrences may be post-infectious in nature at this point of the pandemic. (3) Mostly GAD and VGKC antibodies have been identified (10 of them), which may point toward a new direction of research from a molecular mimicry standpoint. (4) To benefit patients, clinicians need to be aware of such disease manifestations and increase testing; resources must be increased to improve test availability and shorten turnaround time; and treatment, which is expansive, must be made widely available for these potentially reversible diseases.

Post-infectious basal ganglia encephalitis and axonal variant of Guillain-Barré syndrome after COVID-19 infection: an atypical case report

Neurological complications attributed to coronavirus disease-19 (COVID-19) infection have been reported including acute disseminated encephalomyelitis, Guillain-Barré syndrome, and so on. Herein, we report a 49-year-old woman presented with acute encephalopathy and paraplegia simultaneously after COVID-19 infection. Brain magnetic resonance imaging (MRI) showed symmetric hyperintense basal ganglia lesions on T2-weighted imaging. Cerebrospinal fluid pleocytosis, motor axonal neuropathy and enhancement of conus medullaris nerve roots on spine MRI were observed. We treated her with high-dose corticosteroid and intravenous immunoglobulin.

Herpesvirus-Associated Encephalitis: an Update.

Purpose of ReviewHerpesviruses are a leading cause of encephalitis worldwide. The article reviews the eight human herpesviruses with a focus on recent advances as they pertain to encephalitis.Recent FindingsNotable recent updates include the development of multiplex polymerase chain reaction (PCR)-based panels, which have improved access to PCR tests, especially in rural and resource-limited areas. Despite unchanged treatment recommendations, research is ongoing into novel therapies. There have been recent advances in vaccines, particularly for varicella zoster virus (VZV) which may impact neurologic complications. Finally, the recent discovery of an association between herpes encephalitis and post-infectious autoimmune encephalitis has had a critical impact on the fields of infectious and autoimmune neurology, though there remains much to learn.SummaryMost herpesviruses are neurotropic and must be considered on the differential diagnosis for infectious encephalitis. This article describes recent advances in the diagnosis, treatment, complications, and management of these infections.

Clinical and Genetic Analysis in Pediatric Patients with Multiple Sclerosis and Related Conditions: Focus on DR Genes of the Major Histocompatibility Complex

Introduction: There are several diseases recognized as variants of MS: post-infectious acute disseminated encephalitis, multiple sclerosis (MS), Rasmussen leukoencephalitis and Schilder's leukoencephalitis and related, but separate neuroimmune condition – Neuromyelitis Devic’s. In Kazakhstan diagnosis of such diseases was rare and immune modified treatment was only admitted after the age of 18. Clinical and immunogenetic study of MS spectrum diseases in Kazakhstan would allow to justify early targeted treatment. Objective: The aim of the study was to investigate genes of the main complex of human histocompatibility (MHC) associated with diseases of MS spectrum in Kazakhstani population. Methods: Complex clinical, neuroimaging and immunogenetic studies were performed in 34 children (24 girls, 10 boys) aged 4 to 18 years. 21 children were diagnosed with MS (11 Kazakh origin and 10 – Russian; 4 boys, 17 girls), 7 with leucoencephalitis (all Kazakh, 5 boys, 2 girls) and 6 with Devic neuromyelitis optica (all Kazakh, 1 boy, 5 girls). Genotyping of HLA DRB1, DQA1, DQB1 genes was performed for all patients. Results: MS group was characterized by classical relapsing-remitting MS. Predominant haplotype as a linkage complex was DRB1*15:01~DQA1*01:02~DQB1*06:02 in 20 (47.6%) of 42 DR-alleles, in 16 (76.2%) patients. MS relative risk (RR) was 13,36 for ethnic Kazakhs and RR=5,55 in Russians. Leukoencephalitis had 7 children, with 28.6% mortality rate. The haplotype DRB1*15:01~DQA1*01:02~DQB1*06:02 as a linkage complex was detected 3 patients (4 alleles), RR=5,88. Devic’s neuromyelitis optica (NMO) clinical course was characterized by fast and prolonged progression. There was predominance of DRB1*14 allele with RR=3,38. Conclusion: Summarizing, in the Kazakh population the haplotype DRB1*15:01∼DQA1*01:02∼DQB1*06:02 as a linkage complex was associated with prediction to MS and leukoencephalitis, but not to Devic’s NMO. Our study highlights the importance of awareness of MS and related disorders diagnosis which allows to implement early admission of disease-modified treatment in pediatric MS in Kazakhstan.

Molecular Imaging Findings on Acute and Long-Term Effects of COVID-19 on the Brain: A Systematic Review.

Molecular imaging techniques such as PET and SPECT have been used to shed light on how coronavirus disease 2019 (COVID-19) affects the human brain. We provide a systematic review that summarizes the current literature according to 5 predominant topics. First, a few case reports have suggested reversible cortical and subcortical metabolic alterations in rare cases with concomitant para- or postinfectious encephalitis. Second, imaging findings in single patients with the first manifestations of parkinsonism in the context of COVID-19 resemble those in neurodegenerative parkinsonism (loss of nigrostriatal integrity), but scarceness of data and a lack of follow-up preclude further etiologic conclusions (e.g., unmasking/hastening of neurodegeneration vs. infectious or parainfectious parkinsonism). Third, several case reports and a few systematic studies have addressed focal symptoms and lesions, most notably hyposmia. The results have been variable, although some studies found regional hypometabolism of regions related to olfaction (e.g., orbitofrontal and mesiotemporal). Fourth, a case series and systematic studies in inpatients with COVID-19–related encephalopathy (acute to subacute stage) consistently found a frontoparietal-dominant neocortical dysfunction (on imaging and clinically) that proved to be grossly reversible in most cases until 6 mo. Fifth, studies on post–COVID-19 syndrome have provided controversial results. In patients with a high level of self-reported complaints (e.g., fatigue, memory impairment, hyposmia, and dyspnea), some authors found extensive areas of limbic and subcortical hypometabolism, whereas others found no metabolic alterations on PET and only minor cognitive impairments (if any) on neuropsychologic assessment. Furthermore, we provide a critical appraisal of studies with regard to frequent methodologic issues and current pathophysiologic concepts. Finally, we devised possible applications of PET and SPECT in the clinical work-up of diagnostic questions related to COVID-19.

Pediatric Autoimmune Encephalitis Following COVID-19 Infection.

Similar to the pathogenesis of autoimmune disease, SARS-CoV-2 (COVID-19) infection has been shown to be associated with dysregulated and persistent inflammatory reactions and production of some antibodies. We report 3 pediatric patients found to have serum SARS-CoV-2 antibodies who presented with neurologic findings suggestive of postinfectious autoimmune-mediated encephalitis. All 3 cases showed lymphocytic pleocytosis on cerebrospinal fluid studies and marked improvement in neurologic symptoms after high-dose intravenous corticosteroids. The manifestations of SARS-CoV-2 infection in the pediatric population are still an evolving area of study, and these cases suggest autoimmune-mediated encephalitis as yet another SARS-CoV-2 related complication.

Prevalence, Causes and Management of Encephalitis

Encephalitis is a major cause of morbidity, mortality, and permanent neurological disability in both adults and children. The term "encephalitis" literally means inflammation of part or all of the "brain" or the brain parenchyma. Encephalitis affects people of all ages; however, the incidence is higher in the pediatric population. Although both genders are affected, most studies showed slight dominance in men. There are two main types with different causes: primary or infectious encephalitis can develop when a fungus, virus, or bacteria infects the brain and accounts for approximately 70% of confirmed cases of encephalitis, and secondary or post-infectious encephalitis when the immune system is active and reacts. to a previous infection and mistakenly attacks the brain. The clinical manifestations depend on whether the brain parenchyma or the meninges are predominantly involved and cause an encephalitic or meningitis syndrome. Diagnostic tests should include a lumbar puncture, an MRI of the brain, and an EEG for suspected encephalitis. In encephalitis, a broad differential diagnosis, both infectious and non-infectious, should be considered. These alternatives include malignancy, autoimmune or paraneoplastic diseases (eg, anti-NMDA receptor encephalitis), brain abscess, drug-induced tuberculosis or delirium, neurosyphilis, or bacterial, fungal, protozoal, or helminthic encephalitis. Antiviral medications, such as intravenous acyclovir, are often given at the initial diagnosis of encephalitis before the cause is known. Acyclovir is the best treatment for herpes simplex encephalitis. If medication can be started soon after symptoms appear, the chance of a full recovery is much higher.

Pseudotumor Cerebri Syndrome as a Neurologic Involvement of Multisystem Inflammatory Syndrome in Children: A Case Report

BackgroundCoronavirus disease 2019 may have neurological manifestations including meningitis, encephalitis, post-infectious brainstem encephalitis and Guillain-Barre syndrome. Neuroinflammation has been claimed as a possible cause. Here, we present a child with multisystem inflammatory syndrome in children (MIS-C) who developed pseudotumor cerebri syndrome (PTCS) during the disease course.CaseA 11-year-old girl presented with 5 days of fever, headache and developed disturbance of consciousness, respiratory distress, conjunctivitis and diffuse rash on her trunk. Immunoglobulin M and G antibodies against severe acute respiratory syndrome coronavirus 2 were positive in her serum. She was diagnosed with MIS-C. On day 10, she developed headache and diplopia. Left abducens paralysis and bilateral grade 3 papilledema were observed. Brain magnetic resonance imaging revealed optic nerve head protrusion, globe flattening. She was diagnosed with secondary PTCS. Papilledema and abducens paralysis improved under acetazolamide and topiramate. Neurological examination became normal after 2 months.ConclusionPTCS may emerge related to MIS-C.

Author Response: A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City.

We appreciate the comments by Kumar et al. on our article.1 The referenced Kremer study2 was a retrospective case series and included patients with positive MRI findings only. It is unclear whether the patients with the diagnosis of “encephalitis” met diagnostic or causal criteria outlined by the International Encephalitis Consortium3 and others.4 Indeed, CSF SARS-CoV-2 RT-PCR was negative in 20 patients. In 2 of 3 with CSF pleocytosis (>5 cell/mm3), imaging was performed >2 weeks from symptom onset, possibly representing postinfectious autoimmune encephalitis and not infectious encephalitis. Many of the MRI findings described are nonspecific and can be seen in hypoxic/ischemic brain injury, metabolic encephalopathy, or postseizure. Notably, 100% of “encephalitis” patients required oxygen and 75% had ARDS, suggesting that a proportion of the MRI changes may represent hypoxic/ischemic injury (defined as a global insult due to hypoxemia, hypotension, or cardiac arrest). Although we detected elevated CSF protein in some patients,1 this is nonspecific and can be found in stroke, hemorrhage (or traumatic tap), hypoxic/ischemic injury, diabetes, uremia, tumor, neuropathy, and many other conditions. Because the implications of SARS-CoV-2 neurotropism are far reaching, we believe that it is critical to follow the most rigorous standards and criteria when ascribing encephalitis/meningitis/myelitis to SARS-CoV-2 infection.

Editor's Note: A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City.

Editor's Note: A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City.

The management of patients with neurological diseases during the COVID-19 pandemic

The article discusses the management of patients with various neurological diseases during the COVID-19 pandemic, taking into account the determination of the level of risk of infection. The possibility of increasing the risk of infection in patients with disability, especially with impaired function of the respiratory and bulbar muscles, limited mobility, and the presence of concomitant diseases, is indicated. The recommendations on the treatment of patients with stroke, neuromuscular diseases, inflammatory and autoimmune diseases of the central nervous system, in particular, multiple sclerosis and neuromyelitis optica spectrum disorder (NMOSD), as well as non-inflammatory diseases of the central nervous system (epilepsy, Parkinson’s disease, atypical parkinsonism, dystonia, hereditary spastic paraplegia, infantile cerebral palsy, benign intracranial hypertension) are considered. Interactions of drugs for the treatment of COVID-19 and neurological diseases are given. Potential neurological complications of COVID-19 are overviewed. Potential neurological complications of COVID-19 were noted: anosmia, ageusia, viral meningitis, encephalitis, post-infectious stem encephalitis, acute necrotizing hemorrhagic leukoencephalopathy, Guillain-Barre syndrome, myositis. The importance of the fact that during the COVID-19 pandemic, when examining patients with neurological diseases, clinicians should take into account the possibility of a patient with COVID-19, and also consider it as a differential diagnosis in order to avoid diagnostic errors, prescribe timely treatment and prevent the spread of infection.

Immune-mediated neurological syndromes in SARS-CoV-2-infected patients

BackgroundEvidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore investigated clinical, serological and CSF features of coronavirus disease 2019 (COVID-19) patients with neurological manifestations.MethodsConsecutive COVID-19 patients with neurological manifestations other than isolated anosmia and/or non-severe headache, and with no previous neurological or psychiatric disorders were prospectively included. Neurological examination was performed in all patients and lumbar puncture with CSF examination was performed when not contraindicated. Serum anti-gangliosides antibodies were tested when clinically indicated.ResultsOf the 349 COVID-19 admitted to our center between March 23rd and April 24th 2020, 15 patients (4.3%) had neurological manifestations and fulfilled the study inclusion/exclusion criteria. CSF examination was available in 13 patients and showed lymphocytic pleocytosis in 2 patients: 1 with anti-contactin-associated protein 2 (anti-Caspr2) antibody encephalitis and 1 with meningo-polyradiculitis. Increased serum titer of anti-GD1b antibodies was found in three patients and was associated with variable clinical presentations, including cranial neuropathy with meningo-polyradiculitis, brainstem encephalitis and delirium. CSF PCR for SARS-CoV-2 was negative in all patients.ConclusionsIn SARS-Cov-2 infected patients with neurological manifestations, CSF pleocytosis is associated with para- or post-infectious encephalitis and polyradiculitis. Anti-GD1b and anti-Caspr2 autoantibodies can be identified in certain cases, raising the question of SARS-CoV-2-induced secondary autoimmunity.

Neurological associations of COVID-19.

BackgroundThe COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare.Recent developmentsA growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 2–6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin.Where next?Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease (eg, hypoxic encephalopathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.

Th17 lymphocytes drive vascular and neuronal deficits in a mouse model of postinfectious autoimmune encephalitis

Antibodies against neuronal receptors and synaptic proteins are associated with a group of ill-defined central nervous system (CNS) autoimmune diseases termed autoimmune encephalitides (AE), which are characterized by abrupt onset of seizures and/or movement and psychiatric symptoms. Basal ganglia encephalitis (BGE), representing a subset of AE syndromes, is triggered in children by repeated group A Streptococcus (GAS) infections that lead to neuropsychiatric symptoms. We have previously shown that multiple GAS infections of mice induce migration of Th17 lymphocytes from the nose into the brain, causing blood-brain barrier (BBB) breakdown, extravasation of autoantibodies into the CNS, and loss of excitatory synapses within the olfactory bulb (OB). Whether these pathologies induce functional olfactory deficits, and the mechanistic role of Th17 lymphocytes, is unknown. Here, we demonstrate that, whereas loss of excitatory synapses in the OB is transient after multiple GAS infections, functional deficits in odor processing persist. Moreover, mice lacking Th17 lymphocytes have reduced BBB leakage, microglial activation, and antibody infiltration into the CNS, and have their olfactory function partially restored. Th17 lymphocytes are therefore critical for selective CNS entry of autoantibodies, microglial activation, and neural circuit impairment during postinfectious BGE.

Neurological Associations of COVID-19

Background: The COVID-19 pandemic, caused by SARS-CoV-2, is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. Based on knowledge of other coronaviruses, especially those that caused the SARS and MERS epidemics, we might expect to see rare cases of central nervous system (CNS) and peripheral nervous system (PNS) disease caused by SARS-CoV-2.Recent developments: A growing number of case reports and series describe a wide array of neurological manifestations, but many lack detail, reflecting the challenge of studying such patients. Encephalopathy is relatively common, being reported for 93 patients in total, including 16 (7.5%) of 214 hospitalised COVID-19 patients in Wuhan, China, and 40 (69%) of 58 in intensive care with COVID-19 in France. Encephalitis has been described in 8 patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 is detected in the cerebrospinal fluid of some patients. Anosmia and ageusia are common and may occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 1.6-6% of hospitalised COVID-19 cases. So far, 88 patients have been described, mostly with ischaemic stroke, who frequently have vascular events in the context of a pro-inflammatory hypercoagulable state with elevated CRP, D-dimer, and ferritin.Where next?: Careful clinical, diagnostic and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease, such as hypoxic encephalopathy and critical care neuropathy, from those caused directly or indirectly by the virus; these include infectious, para- and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognising SARS-CoV-2 neurological disease in patients whose respiratory infection is mild or asymptomatic may prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will remain small. However, these patients may be left with severe neurological sequelae. With so much of the population infected, the overall number of neurological patients, and their associated health, social and economic costs, may be large. Healthcare planners and policymakers must prepare for this eventuality. The many ongoing studies investigating the neurological association will increase our knowledge base.