Consensus Clinical Guidance for Diagnosis and Management of Adult COVID-19 Encephalopathy Patients.

Encephalopathy, a common condition among patients hospitalized with COVID-19, can be a challenge to manage and negatively affect prognosis. While encephalopathy may present clinically as delirium, subsyndromal delirium, or coma and may be a result of systemic causes such as hypoxia, COVID-19 has also been associated with more prolonged encephalopathy due to less common but nevertheless severe complications, such as inflammation of the brain parenchyma (with or without cerebrovascular involvement), demyelination, or seizures, which may be disproportionate to COVID-19 severity and require specific management. Given the large number of patients hospitalized with severe acute respiratory syndrome coronavirus-2 infection, even these relatively unlikely complications are increasingly recognized and are particularly important because they require specific management. Therefore, the aim of this review is to provide pragmatic guidance on the management of COVID-19 encephalopathy through consensus agreement of the Global COVID-19 Neuro Research Coalition. A systematic literature search of MEDLINE, medRxiv, and bioRxiv was conducted between January 1, 2020, and June 21, 2021, with additional review of references cited within the identified bibliographies. A modified Delphi approach was then undertaken to develop recommendations, along with a parallel approach to score the strength of both the recommendations and the supporting evidence. This review presents analysis of contemporaneous evidence for the definition, epidemiology, and pathophysiology of COVID-19 encephalopathy and practical guidance for clinical assessment, investigation, and both acute and long-term management.

Clinical characteristics, treatment and long-term prognosis in patients with anti-NMDAR encephalitis.

OBJECTIVES: We aimed to (i) analyse the clinical characteristics, treatment outcome and long-term prognosis of anti-NMDAR encephalitis and (ii) study the differences between paediatric and adult patients. METHODS: This was a chart review of all patients with anti-NMDAR encephalitis. RESULTS: There were 28 patients with 18 patients belonging to the paediatric (<18 years) age group. There was female (94%) preponderance in the paediatric age group, while in adult patients, there was no gender predilection (p=0.006). There was no significant difference in clinical feature, outcome or number of relapses between paediatric and adult population groups. MRI brain was abnormal in 53% of patients. Among the 15 patients with MRI abnormalities at the onset, 53% had poor functional outcome at 1 year, while in 12 patients with normal initial MRI brain, only 8% had poor functional outcome at 1 year (p =0.01). Nearly 53% of patients with abnormal MRI at presentation had at least one clinical relapse within 2 years while in patients with normal MRI at presentation, 15% had a clinical relapse (p=0.037). EEG abnormalities were noticed in 71% of patients; among them, 40 and 15% had poor functional outcome at 1 and 2 years respectively. In comparison, those with normal first EEG at onset, 12% had poor functional outcome at 2 years (p=0.57). CONCLUSIONS: Both paediatric and adult patients presented with similar clinical features but the paediatric population had female preponderance. The functional outcome and number of relapse were comparable in both the paediatric and adult groups. Patients with parenchymal changes on MRI and abnormal EEG showed poorer response compared to those with normal MRI and/or EEG at the onset. Patients have lesser severity of symptoms at relapse than in the first episode. An early diagnosis and treatment are essential for better long-term functional outcome.

Abnormalities of white and grey matter in early multiple system atrophy: comparison of parkinsonian and cerebellar variants.

OBJECTIVE: Multiple system atrophy (MSA) is a neurodegenerative disorder with progressive motor and autonomic dysfunction. There is a paucity of information on the early neurostructural changes in MSA, especially its subtypes, MSA-P (patients with predominant parkinsonism) and MSA-C (patients with predominant cerebellar signs). This study investigates the abnormalities of grey matter (GM) and white matter (WM) in early MSA and its subtypes using multi-modal voxel-based analysis. MATERIALS AND METHODS: Twenty-six patients with MSA with duration of symptoms ≤ 2.5 years (mean duration: 1.6 ±0.9 years) were assessed clinically and with 3T MRI. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) were performed to identify the structural changes in MSA and its subtypes. The GM changes and diffusion parameters of WM tracts were correlated with the clinical scores. The results were compared with MRI of 25 age- and gender-matched healthy controls. RESULTS: The early structural changes in MSA included GM loss of the cerebellum and subcallosal gyrus with widespread involvement of supratentorial and infratentorial WM fibres. In MSA-C, GM loss was limited to the cerebellum with WM changes predominantly affecting the infratentorial WM and association tracts. In contrast, MSA-P did not demonstrate any GM loss and the WM involvement was mainly supratentorial. There was no significant correlation between structural changes and clinical severity score. CONCLUSION: In early MSA, WM microstructure was more affected than GM. These changes were greater in MSA-C than in MSA-P, suggesting variable deterioration in the subtypes of MSA. KEY POINTS: • Structural changes in early multiple system atrophy were evaluated using multi-modal neuroimaging. • White matter was more affected than grey matter in early MSA. • Clinical variables did not correlate with early structural changes.

Evaluation of Cognition and Cortical Excitability in Huntington's Disease.

BACKGROUND: Recent advances in neurophysiological techniques have contributed to our understanding of the pathophysiology of Huntington's disease (HD). Studies of the motor cortical excitability and central motor pathways have shown variable results. OBJECTIVES: Our aims were to evaluate the cortical excitability changes in HD using transcranial magnetic stimulation (TMS) and correlate the changes with cognitive impairment. METHODS: The study included 32 HD patients and 30 age- and gender-matched controls. The demographic and clinical profiles of the patients were recorded. All subjects were evaluated by TMS and resting motor threshold (RMT), central motor conduction time (CMCT), silent period (SP), short-interval intracortical inhibition (SICI), and intracortical facilitation were determined. A battery of neuropsychological tests was administered to all subjects. RESULTS: The mean age of the patients was 42.1±14.1 years, and that of controls 39.4±12.4 years (p=0.61). There was no significant difference in RMT and CMCT between the two groups. There was a mild prolongation of the contralateral SP in HD, but it was not significant. SICI was significantly reduced in HD (p<0.0001). A significant impairment in attention, verbal fluency, executive function, visuospatial function, learning, and memory was observed in HD patients. However, there was no correlation between cortical excitability changes and cognitive impairment. CONCLUSIONS: TMS is a valuable method of evaluating cortical excitability changes in HD. These patients have reduced SICI and significant impairment of cognition in multiple domains.

Six decades of Neurology at NIMHANS: A historical perspective.

The Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka has a long tradition of excellence in education, teaching, research, and patient care. Its exceptional alumni, as well as current and past faculty members, have made considerable contributions to the development of neurological services throughout the world. The six decades of its existence have seen a momentous growth in clinical, investigative, and community Neurology. As a result of the immense scientific individual as well as collaborative contributions of the faculty members in various departments, the Institute has had the honour of attaining the status of an autonomous 'Institute of National Importance' under the Ministry of Health, Government of India, through a novel concept of collaboration and partnership of central and state governments. This article traces the dedicated pursuit of members of the Department of Neurology, NIMHANS, in managing neurologic diseases through compassionate patient-centred care, transformative research and education.

Review of tremor in Parkinson's disease and atypical parkinsonian disorders.

Rest tremor (RT), a cardinal feature of Parkinson's disease (PD) is often accompanied by other types of tremor such as action tremor, which includes postural tremor, kinetic tremor, re-emergent tremor (ReT), and orthostatic tremor (OT). Literature on other tremors of PD, especially ReT and OT, is scarce. Tremor can be present in any of the atypical parkinsonian disorders such as progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and dementia with Lewy bodies. RT can even be the presenting symptom of these disorders. The objective of this review is to provide a comprehensive review of lesser known tremors in PD and to critically look at the prevalence of tremor in atypical Parkinsonian disorders.

Gender and Age Determinants of Psychogenic Movement Disorders: A Clinical Profile of 73 Patients.

BACKGROUND: Psychogenic movement disorders (PMD) is a group of disorders that cannot be attributed to any structural or biochemical abnormality, but has an underlying psychiatric illness. The profile of PMD varies according to country and socioeconomic factors. METHODS: The present study reports the clinical profile of patients with PMD from India. Seventy-three patients with documented or clinically established PMD were seen over a period of 14 years with detailed neurological and psychiatric examinations. RESULTS: The mean age at presentation was 29.1±15.1 years (women, 51%). Approximately 30% were ≤18 years of age (boys, 63.6%). The onset of symptoms was abrupt in 61.6% and the initial body part most often affected was right upper limb (adults, 29.4%; children, 31.8%). Tremor was observed in 31.4% of adults and 9% of children, whereas myoclonus was more common in children (36.4%). Tremors were more often seen in women (42.3%) than in men (20%), whereas myoclonus was almost equally prevalent in girls (37.5%) and boys (35.7%). Depression was the most common psychiatric comorbidity (men, 16%; women, 15.4%). About 42.5% required hospital admission and 57.5% had significant reduction or complete cessation of PMD after counseling, antidepressants, and/ or placebo. CONCLUSIONS: PMD was equally prevalent among women and men. Tremor was most often observed in adults, whereas myoclonus was most often observed in children. Electrophysiology and placebo were useful supplementary tools for diagnosing PMD.

Dengue encephalitis with predominant cerebellar involvement: report of eight cases with MR and CT imaging features.

OBJECTIVES: CNS dengue infection is a rare condition and the pattern of brain involvement has not been well described. We report the MR imaging (MRI) features in eight cases of dengue encephalitis. MATERIALS AND METHODS: We retrospectively searched cases of dengue encephalitis in which imaging was performed. Eight cases (three men, five women; age range: 8-42 years) diagnosed with dengue encephalitis were included in the study. MR studies were performed on 3-T and 1.5-T MR clinical systems. Two neuroradiologists retrospectively reviewed the MR images and analysed the type of lesions, as well as their distribution and imaging features. RESULTS: All eight cases exhibited MRI abnormalities and the cerebellum was involved in all cases. In addition, MRI signal changes were also noted in the brainstem, thalamus, basal ganglia, internal capsule, insula, mesial temporal lobe, and cortical and cerebral white matter. Areas of susceptibility, diffusion restriction, and patchy post-contrast enhancement were the salient imaging features in our cohort of cases. CONCLUSION: A pattern of symmetrical cerebellar involvement and presence of microbleeds/haemorrhage may serve as a useful imaging marker and may help in the diagnosis of dengue encephalitis.

Clinical and imaging characteristics of 16 patients with autoimmune neuronal synaptic encephalitis.

OBJECTIVES: Autoimmune neuronal synaptic encephalitis (AIE) encompasses a heterogeneous group of disorders characterized by immune-mediated neuronal cell destruction. In this study, we aim to study the clinical features, imaging profile and treatment outcome of patients with AIE. METHODS: This is a chart review of 16 (M: F-3:13) patients with AIE from 2011 to 2015. RESULTS: Among the patients, 10 had anti-NMDA, 4 had anti-TPO, and 2 had anti-VGKC antibody positivity. Cognitive impairment and seizures were the predominant symptoms present in nearly all patients, followed by psychiatric disturbances (87.5%), mutism (62.5%), movement disorders (62.5%), myoclonic jerks (37.5%) and visual hallucinations (18.75%). Magnetic resonance imaging (MRI) of the brain was available in 15 patients; it was abnormal in 53.3% patients. Abnormalities were seen in all patients with anti-VGKC positivity; and, 60% of patients with anti-NMDA positivity. Imaging was normal in 26.7% of the patients (3: anti-NMDA; and, 1: anti-TPO positivity); and, diffuse cerebral atrophy was noted in rest of the 20% (3: anti-TPO positivity) patients. All patients improved gradually with immunomodulation. CONCLUSIONS: All patients with anti-VGKC, anti-NMDA and anti-TPO antibody positivity presented with a triad of behavioral changes, impaired cognition and seizures. Mutism was a predominant symptom in patients with an anti-NMDA antibody positivity, which may help in the early identification of this disorder. MRI brain showed changes restricted to limbic structures in anti-NMDA and anti-VGKC antibody positivity. An early diagnosis and treatment of autoimmune encephalitis is essential for a better outcome and for prevention of long-term sequel.

Clinicopathological Features in Morvan's Syndrome: An Autopsy Case Study.

Morvan's syndrome is a rare, complex autoimmune syndrome comprising peripheral nerve hyperexcitability, dysautonomia, insomnia, and encephalopathy. In this case report, we highlight the clinical and pathological findings of an elderly gentleman who presented to us with clinical features of Morvan's syndrome associated with anti-contactin-associated protein 2 (CASPR-2) antibodies. Histopathology [Figure 3] revealed cortical atrophy with gliosis and mild microglial proliferation. Microglial activation and gliosis were observed in the hippocampus, hypothalamus, and thalamus. Brainstem showed multifocal inflammation. Mild inflammation was observed in the leptomeninges. Morvan's syndrome is an autoimmune disease with antibodies targeted against CASPR within the voltage-gated potassium channel (VGKC) complex. Early diagnosis and treatment play a key role in the management of patients. Most patients show a good response when treated with plasmapheresis and steroids. This patient presented to us late into the illness and succumbed.

Are monoclonals the only panacea for treatment of aquaporin-4 positive NMOSD? Experience from a low-&middle-income (LMIC) region.

OBJECTIVE: A plethora of monoclonals have ushered up for NMOSD treatment. However, their limited availability and cost concerns poses a challenge for usage in developing nations. We compared relapse rates and disabilities among aquaporin-4 positive(AQP4+ve) patients on conventional immunosuppressants and rituximab in a tertiary referral center in southern India. METHODS: This was a chart review of AQP4+ve patients registered under national demyelination registry maintained at institute. AQP4+ve patients were included if they were on azathioprine, MMF, methotrexate for six months; cyclophosphamide for three months and rituximab for one month. RESULTS: 207 records were screened, 154 fulfilled inclusion criteria. Drugs used were azathioprine (70), MMF (34) and rituximab (33). All three drugs were non-inferior to each other in terms of ARR reduction. Median EDSS at last follow-up was significantly lower for azathioprine(2;IQR:0-5) and rituximab(2;IQR:0.5-5) than MMF(3.5;IQR:2-5.6), however azathioprine was associated with highest switch rate(34.3%) and was the only drug which required change because of intolerance. Failure rate was least for rituximab(27.3%).Patients on azathioprine and MMF required higher mean duration of concurrent steroids(7.8±7.7 and 4.56±2.17 months respectively) when compared to rituximab(2.77±1.38) and had more relapses due to steroid withdrawal. CONCLUSION: Initial treatment with azathioprine, MMF and rituximab is comparable in terms of ARR reduction. Findings suggest that choice may be guided by adverse event profile of drug, rather than efficacy per se. Concurrent treatment duration with steroids should also guide clinical decision. Switch to second immunomodulation in event of initial failure adds to efficacy benefit, irrespective of the drug chosen.

The co-occurrence of multiple sclerosis and bipolar disorder: A case series on clinical and neuroimaging correlates.

There is a dearth of studies on neuroimaging correlates of Bipolar Disorder (BD) in Multiple Sclerosis (MS). We describe the clinical profile and neuroimaging findings of four cases of MS with BD. Among them, two patients had multiple mood episodes preceding the neurological symptoms, one had concurrent manic and neurological symptoms, and one had multiple depressive episodes and an isolated steroid-induced manic episode. Frontal and temporal lobes, and Periventricular White Matter were involved in all four cases, and hence may be considered biological substrates of BD in MS. Larger studies are needed to validate the utility of these findings.

Progressive multifocal leukoencephalopathy (PML) associated with HIV Clade C--is not uncommon.

Progressive multifocal leukoencephalopathy (PML) is a rare, subacute, demyelinating disease of the central nervous system caused by JC virus. Studies of PML from HIV Clade C prevalent countries are scarce. We sought to study the clinical, neuroimaging, and pathological features of PML in HIV Clade C patients from India. This is a prospective cum retrospective study, conducted in a tertiary care Neurological referral center in India from Jan 2001 to May 2012. Diagnosis was considered "definite" (confirmed by histopathology or JCV PCR in CSF) or "probable" (confirmed by MRI brain). Fifty-five patients of PML were diagnosed between January 2001 and May 2012. Complete data was available in 38 patients [mean age 39 ± 8.9 years; duration of illness-82.1 ± 74.7 days). PML was prevalent in 2.8 % of the HIV cohort seen in our Institute. Hemiparesis was the commonest symptom (44.7 %), followed by ataxia (36.8 %). Definitive diagnosis was possible in 20 cases. Eighteen remained "probable" wherein MRI revealed multifocal, symmetric lesions, hypointense on T1, and hyperintense on T2/FLAIR. Stereotactic biopsy (n = 11) revealed demyelination, enlarged oligodendrocytes with intranuclear inclusions and astrocytosis. Immunohistochemistry revelaed the presence of JC viral antigen within oligodendroglial nuclei and astrocytic cytoplasm. No differences in clinical, radiological, or pathological features were evident from PML associated with HIV Clade B. Clinical suspicion of PML was entertained in only half of the patients. Hence, a high index of suspicion is essential for diagnosis. There are no significant differences between clinical, radiological, and pathological picture of PML between Indian and Western countries.

Comparative evaluation of ELISA and dot-blot for the diagnosis of tuberculous meningitis.

Tuberculous meningitis is a central nervous system tuberculosis caused by M. tuberculosis. It causes high mortality if delayed in diagnosis and treatment. In this comparative study, Cerebrospinal fluid from TBM and non TBM patients were analyzed by ELISA and Dot-blot for anti-tuberculous antibodies. About 70% of the TBM samples showed positivity by Dot-blot and 72.5% by ELISA. Among the non TBM controls, 2.9% showed positivity by Dot-blot and 4.4% by ELISA. Both methods did not differ significantly as seen by Fisher's exact test (p = 0.50). Thus, Dot-blot could be an easy alternative to ELISA for quick diagnosis of TBM.

Double hit - A case in point for dual seropositivity to AQP4 and MOG antibodies.

AQP4-IgG NMOSD (anti-aquaporin-4 neuromyelitis optica spectrum disorder) and MOGAD (myelin oligodendrocyte glycoprotein antibody associated disease) are unique disorders among themselves, with rare reports of dual seropositivity being described. Evaluation with cell-based assays reduces the incidence of false positivity. The clinical features of these cases may either have a dominant phenotype or may evolve into one subsequently. We describe a young girl aged 18-year-old who presented with longitudinally extensive transverse myelitis and dual seropositivity to both AQP4 and MOG antibodies.

Japanese Encephalitis among Adults: A Review.

Japanese encephalitis (JE) is becoming an increasingly important issue among adults. The reasons for this are multifactorial. During the past decades, new areas of Japanese encephalitis virus (JEV) transmission have occurred in several locations, most notably in a markedly expanded area of Australia during 2021-2022. When JEV enters new areas, cases in adults frequently occur. This is unlike the typical pattern in endemic areas where the burden of disease is in children because most adults are protected through natural immunity following earlier exposure to the virus. Even in endemic areas, JEV has become relatively more important in adults because improved JE control through childhood immunization programs has resulted in a substantial decrease in pediatric JE cases and thus more prominence of adult JE cases. Finally, increases in tourism to JE risk areas have resulted in more exposure of adult travelers, who are usually non-immune, to infection in JE risk areas. In this review we describe the increasing importance of JE in adults in some areas and then consider the comparative clinical presentation and severity of illness among children and adults.

Profile of Acute Encephalitis Syndrome Patients from South India.

Introduction: Encephalitis is a major public health problem worldwide that causes huge emotional and economic loss to humanity. Encephalitis, being a serious illness, affects people of all ages. The aim is to describe the sociodemographic, clinical, etiological, and neuroimaging profile among 101 acute encephalitis syndrome (AES) patients visiting a tertiary neuro-specialty care hospital in India. Methods: Record review of medical records of all patients attending neurology emergency and outpatient services at NIMHANS Hospital, diagnosed with AES in 2019, was conducted. Data were collected using standardized data collection forms for all cases in the study. Descriptive analyses (mean and standard deviation for continuous variables and proportions for categorical variables) were conducted. The Chi-square test/Fisher's exact test was used for the comparison of independent groups for categorical variables, and t-test for comparing means for continuous variables. Results: About 42.6% of AES patients had viral etiology, while in 57.4%, etiology was not ascertained. Common presenting symptoms were fever (96%), altered sensorium (64.4%), seizures (70.3%), headache (42.6%), and vomiting (27.7%). Herpes simplex was the most common (21.8%) identified viral encephalitis, followed by chikungunya (5%), arboviruses (chikungunya and dengue) (4%), Japanese encephalitis (4%), rabies (3%), dengue (1%), and varicella virus (1%). About 40% of AES patients showed cerebrospinal fluid pleocytosis (44%), increased protein (39.6%), abnormal computed tomography brain (44.6%), and magnetic resonance imaging abnormalities (41.6%). Conclusion: The study highlights the need to ascertain etiology and importance of evidence-based management of AES patients. A better understanding of opportunities and limitations in the management and implementation of standard laboratory and diagnostic algorithms can favor better diagnosis and management of AES.

Co-VAN study: COVID-19 vaccine associated neurological diseases- an experience from an apex neurosciences centre and review of the literature.

BACKGROUND: Recent studies have shown various neurological adverse events associated with COVID-19 vaccine. OBJECTIVE: We aimed to retrospectively review and report the neurological diseases temporally associated with COVID-19 vaccine. METHODS: We performed a retrospective chart review of admitted patients from 1st February 2021 to 30th June 2022. A total of 4672 medical records were reviewed of which 51 cases were identified to have neurological illness temporally associated with COVID-19 vaccination. RESULTS: Out of 51 cases, 48 had probable association with COVID-19 vaccination while three had possible association. Neurological spectrum included CNS demyelination (n = 39, 76.5 %), Guillain-Barré-syndrome (n = 3, 5.9 %), stroke (n = 6, 11.8 %), encephalitis (n = 2, 3.9 %) and myositis (n = 1, 2.0 %). Female gender had a greater predisposition (F:M, 1.13:1). Neurological events were more commonly encountered after the first-dose (n = 37, 72.5%). The mean latency to onset of symptoms was 13.2 ± 10.7 days after the last dose of vaccination. COVIShield (ChAdOx1) was the most commonly administered vaccine (n = 43, 84.3 %). Majority of the cases with demyelination were seronegative (n = 23, 59.0 %) which was followed by anti-Myelin oligodendrocyte-glycoprotein associated demyelination (MOGAD) (n = 11, 28.2 %) and Neuromyelitis optica (NMOSD) (n = 5, 12.8 %). Out of 6 Stroke cases, 2 cases (33.3 %) had thrombocytopenia and coagulopathy. At discharge, 25/51 (49.0 %) of the cases had favourable outcome (mRS 0 to 1). Among six patients of stroke, only one of them had favourable outcome. CONCLUSION: In this series, we describe the wide variety of neurological syndromes temporally associated with COVID-19 vaccination. Further studies with larger sample size and longer duration of follow-up are needed to prove or disprove causality association of these syndromes with COVID-19 vaccination.