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Objective The objective of this study was to evaluate patients with ganglionic acetylcholine receptor antibody (gAChR-Ab) positive autoimmune autonomic ganglionopathy using a multimodal testing protocol to characterize their full clinical phenotype and explore biomarkers to quantify immunotherapy response. Methods We conducted a cohort study of 13 individuals (7 women, 21-69 years of age) with autonomic failure and gAChR-Ab >100 pM identified between 2005 and 2019. From 2018, all patients were longitudinally assessed with cardiovascular, pupillary, urinary, sudomotor, lacrimal and salivary testing, and Composite Autonomic Symptom Score (COMPASS-31) autonomic symptom questionnaires. The orthostatic intolerance ratio was calculated by dividing change in systolic blood pressure over time tolerated on head-up tilt. Eleven patients received immunotherapy. Results At first assessment, all 13 patients had cardiovascular and pupillary impairments, 7 of 8 had postganglionic sudomotor dysfunction, 9 of 11 had urinary retention and xeropthalmia, and 6 of 8 had xerostomia. After immunotherapy, there were significant improvements in orthostatic intolerance ratio (33.3 [17.8-61.3] to 5.2 [1.4-8.2], p = 0.007), heart rate response to deep breathing (1.5 [0.0-3.3] to 4.5 [3.0-6.3], p = 0.02), pupillary constriction to light (12.0 [5.5-18.0] to 19.0 [10.6-23.8]%, p = 0.02), saliva production (0.01 [0.01-0.05] to 0.08 [0.02-0.20] g/min, p = 0.03), and COMPASS-31 scores (52 to 17, p = 0.03). Orthostatic intolerance ratio correlated with autonomic symptoms at baseline (r = 0.841, p = 0.01) and following immunotherapy (r = 0.889, p = 0.02). Immunofluorescence analyses of skin samples from a patient 32 years after disease onset showed loss of nerve fibers supplying the dermal autonomic adnexa and epidermis, with clear improvements following immunotherapy. Interpretation Patients with autoimmune autonomic ganglionopathy demonstrated objective evidence of widespread sympathetic and parasympathetic autonomic failure, with significant improvements after immunotherapy. Quantitative autonomic biomarkers should be used to define initial deficits, guide therapeutic decisions, and document treatment response. ANN NEUROL 2021;89:753-768.

N-methyl-d-aspartate receptor antibody (NMDAR-Ab) encephalitis consensus criteria has recently been defined. We aimed to examine the prevalence of NMDAR-Ab encephalitis in patients with first episode psychosis (FEP) and treatment resistant schizophrenia (TRS) on clozapine, using clinical investigations, antibody testing and to retrospectively apply diagnostic consensus criteria.Adult (18-65 years old) cases of FEP meeting inclusion criteria were recruited over three years and assessed using the Structured Clinical Interview for DSM-IV disorders (SCID). NMDAR-Ab was identified using a live cell-based assay (L-CBA). Seropositive cases were clinically investigated for features of encephalitis including neuro-imaging, EEG and CSF where possible. Serum was retested using immunohistochemistry (IHC) as part of diagnostic criteria guidelines. A cohort of patients with TRS was also recruited.112 FEP patients were recruited over 3 years. NMDAR-Ab seroprevalence was 4/112 (3.5%) cases. One case (1%) was diagnosed with definite NMDAR-Ab encephalitis and treated with immunotherapy. One of the three other seropositive cases met criteria for probable encephalitis. However all three were ultimately diagnosed with mood disorders with psychotic features. None have developed neurological features at three year follow up. 1/100 (1%) of patients with TRS was 100 patients with TRS were recruited. One case (1%) seropositive for NMDAR-Ab but did not meet criteria for encephalitis.NMDAR-Ab encephalitis as defined by consensus guidelines occured rarely in psychiatric services in this study. Further studies are needed to establish pathogenicity of serum NMDAR-Ab antibodies. Psychiatric services should be aware of the clinical features of encephalitis.

IntroductionPost-COVID-19 complications require simultaneous characterisation and management to plan policy and health system responses. We describe the 12-month experience of the first UK dedicated post-COVID-19 clinical service to include hospitalised and non-hospitalised patients.MethodsIn a single-centre, observational analysis, we report the demographics, symptoms, comorbidities, investigations, treatments, functional recovery, specialist referral and rehabilitation of 1325 individuals assessed at the University College London Hospitals post-COVID-19 service between April 2020 and April 2021, comparing by referral route: posthospitalised (PH), non-hospitalised (NH) and post emergency department (PED). Symptoms associated with poor recovery or inability to return to work full time were assessed using multivariable logistic regression.Results1325 individuals were assessed (PH: 547, 41.3%; PED: 212, 16%; NH: 566, 42.7%). Compared with the PH and PED groups, the NH group were younger (median 44.6 (35.6–52.8) years vs 58.3 (47.0–67.7) years and 48.5 (39.4–55.7) years), more likely to be female (68.2%, 43.0% and 59.9%), less likely to be of ethnic minority (30.9%, 52.7% and 41.0%) or seen later after symptom onset (median (IQR): 194 (118–298) days, 69 (51–111) days and 76 (55–128) days; all pConclusionPost-COVID-19 symptoms were significant in PH and NH patients, with significant ongoing healthcare needs and utilisation. Trials of interventions and patient-centred pathways for diagnostic and treatment approaches are urgently required.

BackgroundComplications following SARS-CoV-2 infection require simultaneous characterisation and management to plan policy and health system responses. We describe the 12-month experience of the first UK dedicated Post-COVID clinical service to include both hospitalised and non-hospitalised patients.MethodsIn a single-centre, observational analysis, we report outcomes for 1325 individuals assessed in the University College London Hospitals NHS Foundation Trust Post-COVID service between April 2020 and April 2021. Demography, symptoms, comorbidities, investigations, treatments, functional recovery, specialist referral and rehabilitation were compared by referral route (“post hospitalisation”, PH; “non-hospitalised”, NH; and “post emergency department”, PED). Symptoms associated with poor recovery or inability to return to work full-time were assessed using multivariable logistic regression.Findings1325 individuals were assessed (PH 547 [41.3%], PED 212 [16%], NH 566 [42.7%]. Compared with PH and PED groups, NH were younger (median 44.6 [35.6-52.8] vs 58.3 [47.0-67.7] and 48.5 [39.4-55.7] years), more likely to be female (68.2%, 43.0% and 59.9%), less likely to be from an ethnic minority (30.9%, 52.7% and 41.0%) and seen later after symptom onset (median [IQR]:194 [118-298], 69 [51-111] and 76 [55-128] days) (all pInterpretationSymptoms following SARS-CoV-2 infection were significant in both post- and non-hospitalised patients, with significant ongoing healthcare needs and utilisation. Trials of interventions and patient-centred pathways for diagnostic and treatment approaches are urgently required.FundingUCLH/UCL BRCResearch in contextPrevious evidenceLong COVID and post-COVID syndrome were first identified in April 2020. We searched PubMed and medrxiv for articles published up to April 30th, 2021, using the keywords “long COVID”, “post-COVID syndrome”, “persistent symptoms”, “hospitalised”, “community” and “non-hospitalised”. We identified 17 articles and 7 systematic reviews. Fifteen studies have considered symptoms, multi-organ or functional impairment but only one study to-date has considered all these variables in non-hospitalised COVID patients. No studies have compared symptom burden and management between non-hospitalised and hospitalised individuals as systematically assessed and managed in a dedicated post-COVID service.Added value of this studyFor the first time, we report the baseline characteristics, investigation and outcomes of initial assessment of all eligible patients in a dedicated multi-professional post-COVID service, including 547 post-hospitalisation, 566 non-hospitalised and 212 patients discharged from emergency department. Despite relatively low comorbidity and risk factor burden in non-hospitalised patients, we show that both non-hospitalised and hospitalised patients presenting with persistent symptoms after SARS-CoV2 infection have high rates of functional impairment, specialist referral and rehabilitation, even 6-12 months after the acute infection. These real-world data will inform models of care during and beyond the pandemic.Implications of all the available evidenceThe significant, long-lasting health and social consequences of SARS-CoV-2 infection are not confined to those who required hospitalisation. As with other long-term conditions, care of patients experiencing Long COVID or specific end-organ effects require consistent, integrated, patient-centred approaches to investigation and management. At public health and policy level, burden of post-COVID morbidity demands renewed focus on effective infection suppression for all age groups.

Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC) is a rare autosomal recessive condition characterised by early-onset severe progressive neuropathy, variable degrees of ACC and cognitive impairment. Mutations in SLC12A6 (solute carrier family 12, member 6) encoding the K+–Cl- transporter KCC3 have been identified as the genetic cause of HMSN/ACC. We describe fraternal twins with compound heterozygous mutations in SLC12A6 and much milder phenotype than usually described. Neither of our patients requires assistance to walk. The female twin is still running and has a normal intellect. Charcot-Marie-Tooth Examination Score 2 was 8/28 in the brother and 5/28 in the sister. Neurophysiology demonstrated a length-dependent sensorimotor neuropathy. MRI brain showed normal corpus callosum. Genetic analysis revealed compound heterozygous mutations in SLC12A6, including a whole gene deletion. These cases expand the clinical and genetic phenotype of this rare condition and highlight the importance of careful clinical phenotyping.

Objectives The objective of this study was to establish the level of awareness of HAND among healthcare providers, the screening tools that are currently used in its detection and factors that limit cognitive assessments. Methods We distributed a 12-item questionnaire to doctors and nurses who work in the Department of Genitourinary Medicine and Infectious Disease (GUIDE) service and also to doctors who work in the emergency department (ED) at St James Hospital. Results 35 surveys were collected, 54% (n = 19) from the GUIDE service and 46% (n = 16) from the ED. 82% (n = 29) of participants were doctors from interns to consultants. There was reasonable appreciation among participants with regards the prevalence of neurocognitive impairment (estimated at 29.1% among patients on HAART, and 39.3% among patients not on HAART). Screening tools were rarely used by GUIDE and ED clinicians (25% vs. 15% of the time). The Mini Mental State Examination (MMSE) was previously used by 37% (n = 13) of the group. Very few people had used the HIV Dementia Scale (HIVDS) 6% (n = 2). 34% of respondents felt that ‘Orientation in Person, Place and Time was a sufficient screening tool for cognitive assessment’. Lack of time, exposed environment and lack of availability of screening tool were cited as limitations to cognitive screening in the ED environment. Conclusions This study examines awareness of HAND among healthcare providers and also reasons for inadequate assessment. There is a need for consensus on screening guidelines. A quick, easy to use and readily available screening tool may have a role in the acute setting in identifying high-risk patients.

Background Human immunodeficiency virus (HIV)-associated neurocognitive disorders occurs in 20%–50% of HIV-positive patients. We undertook this study to assess the prevalence of a positive screen for cognitive impairment in the clinic population at our institution and to demonstrate the feasibility of implementing a screening program in routine clinical encounters. Methods This was a cross-sectional study, and patients were recruited prospectively between December 2010 and February 2013. Inclusion criteria were as follows: patients were HIV positive, over the age of 18, capable of giving informed consent, and had sufficient ability to communicate in English. Patients were screened for cognitive impairment using the Brief Neurocognitive Screen. Results A total of 604 patients were recruited, and 51.5% had a positive screen for cognitive impairment. The majority of the study cohort were male (78.8%), mean age was 40.9 (standard deviation, 10.2) years, 70.9% were Irish, the most common mode of transmission was men who have sex with men (49.3%), 83% were on antiretroviral therapy, and 88.7% were virally suppressed. Logistic regression showed that the main factors predictive of a positive screen for cognitive impairment were the endorsement of cognitive symptoms (P = .024), being born in Africa (P < .000001), the use of benzodiazepines (P = .00341), being unemployed (P = .008), and consumption of more than 40 units of alcohol weekly (P = .035). There was a positive screen for depression in 9.1% and a positive screen for anxiety in 24.5%. Conclusions The study highlights the necessity for a structured, prospective, large-scale screening program for cognitive impairment across countries with limited resources and demonstrates the feasibility of easily implementing this with minimal training.

High levels of cardiovascular fitness and physical activity are associated with higher levels of cognitive function in people with HIV, thus, they may reduce the risk of developing HIV-associated neurocognitive disorder (HAND). This study aimed to investigate the effects of a 16-week aerobic exercise intervention on cognitive function in people with HIV. Eleven participants living with HIV were recruited into the study. Participants were randomised into either an exercise group (n = 5), that completed a 16-week aerobic exercise programme training, 3 times per week (2 supervised sessions and one unsupervised session) or a control group (n = 6) that received no intervention. Outcomes measured included cognitive function (Montreal cognitive assessment (MOCA) and the Trail making tests A and B), aerobic fitness (modified Bruce protocol), sleep quality (Pittsburgh sleep quality index; PSQI) and physical activity levels (seven-day accelerometry). At baseline, higher levels of moderate physical activity were positively correlated with higher MOCA scores and levels of aerobic fitness were negatively associated with Trail A scores (P = 0.04 and P = 0.001 respectively). However, exercise training did not induce any significant improvements in cognitive function or aerobic fitness. The overall mean adherence rate to the exercise programme was 60%. In conclusion, in the present study a 16-week aerobic exercise intervention did not affect the cognitive function of participants with HIV. It is likely that longer intervention periods and/or higher adherence rates to exercise might be needed for an aerobic exercise programme to be effective in improving cognitive function in a cohort with no baseline cognitive impairments.

Aim. To evaluate the utility of a seizure care pathway for seizure presentations to the emergency department (ED) in order to safely avoid unnecessary admission and to provide early diagnostic and therapeutic guidance and minimize length of stay in those admitted. Methods. 3 studies were conducted, 2 baseline audits and a 12-month intervention study and prospective data was collected over a 12-month period (Nov 2008-09). Results. Use of the Pathway resulted in a reduction in the number of epilepsy related admissions from 341 in 2004 to 276 in 2009 ( 𝑃 = 0 . 0 0 0 6 ); a reduction in the median length of stay of those admittedfrom 4-5 days in the baseline audits to 2 days in the intervention study ( 𝑃 ≤ 0 . 0 0 1 ); an improvement in time to diagnostic investigations such as CT brain, MRI brain and Electroencephalography ( 𝑃 ≤ 0 . 0 0 1 , 𝑃 ≤ 0 . 0 4 8 , 𝑃 ≤ 0 . 0 0 1 ); a reduction in readmission rates from 45.1% to 8.9% ( 𝑃 ≤ 0 . 0 0 1 ); and an improvement in follow-up times from a median of 16 weeks to 5 weeks ( 𝑃 0 . 0 0 1 ). From a safety perspective there were no deaths in the early discharged group after 12 months follow-up. Conclusion. The burden of seizure related admissions through the ED can be improved in a safe and effective manner by the provision of a seizure care pathway.

This chapter outlines common infective causes of cognitive impairment and dementia; HIV, syphilis, toxoplasma, cryptococcosis, Whipple’s disease and hepatitis C. Their clinical presentations, neuropsychological profiles, imaging findings and CSF findings are discussed.

CRANIum, a cross-sectional epidemiology study in Western Europe and Canada, was conducted to describe and compare the prevalence of a positive screen for neurocognitive impairment (NCI), depressive symptoms, and anxiety in an HIV-positive population either receiving combination antiretroviral therapy (cART) or who were naive to antiretroviral therapy (ART). HIV-positive patients ≥18 years of age attending a routine medical follow-up visit and able to complete the designated screening tools were eligible for study inclusion. The Brief Neurocognitive Screen was used to assess NCI; depressive and anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale. The evaluable patient population (N = 2863) included 1766 men (61.7%) and 1096 (38.3%) women. A total of 1969 patients were cART-experienced (68.8%), and 894 were ART-naive (31.2%). A positive screen for NCI was found in 41.5% of patients (cART-experienced, 42.5%; ART-naive, 39.4%; p = 0.12). A positive screen for depressive symptoms was found in 15.7% of patients (cART-experienced, 16.8%; ART-naive, 13.3%; p = 0.01), whereas 33.3% of patients screened positive for anxiety (cART-experienced, 33.5%; ART-naive, 32.8%; p = 0.71). A greater percentage of women compared with men screened positive for NCI (51.78% vs. 35.1%; p < 0.0001) and depressive symptoms (17.9% vs. 14.3%; p = 0.01). These data suggest that neurocognitive and mood disorders remain highly prevalent in HIV-infected patients. Regular mental health screening in this population is warranted.

Purpose of the study The prevalence of neurocognitive impairment (NCI) in people living with HIV has previously been reported between 20-50%, with prevalence rates of depression reported between 12-71%. The primary objective of the CRANIum study was to describe the prevalence of a positive screen for NCI and depression/anxiety in an HIV-1-infected adult population, comparing ARV-naive and -experienced patients. Here we present an ethnicity analysis of the CRANIum data. Methods : The study was an epidemiologic, cross-sectional study that included HIV-1-infected patients >18 years old attending a routine clinic visit. One-third of patients were ART-naive, one-third on a PI/r- and one-third on a NNRTI-based regimen. The Brief Neurocognitive Screen (BNCS) was used to screen for NCI. It consists of the Digit Symbol and Trailmaking A and B tests. A standard deviation of >1 on 2 tests or >2 on 1 test was considered a positive screen for NCI. The Hospital Anxiety and Depression Scale (HADS) was used to screen for anxiety (HADS-A) and depression (HADS-D). HADS is self-administered and consists of 14 items (7 HADS-A, 7 HADS-D) scored between 0 to 3. A score of ≥8 was considered as a positive screen for either condition. Summary of results: 2859 evaluable patients were included from 15 countries. Baseline characteristics are shown in table 1 (*p

Introduction Recent literature suggests that over 70% of cases of antibody-mediated encephalitis present to psychiatry services with features of psychosis predominantly. Aim To investigate the seroprevalence of N-Methyl-D-Aspartate receptor antibodies (NMDAr-Ab) in patients with first episode psychosis (FEP) Methods Following ethical approval, all cases meeting entry criteria were invited to participate. Participants were interviewed with SCID to obtain a DSM diagnosis. NMDAr-Ab were identified in serum by cell based assay using co-transfected Human Embryonic Kidney (HEK) cells. Positive cases were reviewed by clinical neurology. Decision to treat with immunotherapy was made on a case by case basis. Results 85/115 (72%) of patients with FEP entered the study. 49 (58%) participants were male, mean age (SD) 37 (15.7) years. 42 (52%) were outpatients at the time of assessment. Four cases (5%) were serum NMDAr-Ab positive. 3 of these cases were male, age 48 (16.3) years. All four were admitted as inpatients with normal brain MRI imaging. One case (female, 55) was confirmed as NMDAr-Ab encephalitis based on case presentation, EEG demonstrating bilateral cerebral dysfunction and NMDAr-Ab in CSF. Immunotherapy treatment lead to clinical improvement. In remaining cases, EEG was normal and CSF negative. All 3 of these cases showed clinical improvement following psychiatric treatment as usual. Discussion Our findings support the current estimates as to NMDAr-Ab prevalence in FEP. Increased awareness has lead to rapid treatment of florid cases of NMDAr-Ab encephalitis in our service. Additional seropositive cases are being followed with neuro-cognitive testing for any evidence of decline.

A 32-year-old woman presented in 2002 with a headache associated with numbness of her right arm, right side of her face and left leg. Examination was normal. Investigations revealed prolonged visual evoked responses (VER) on the right and a low vitamin B12 level. Cerebrospinal fluid (CSF) analysis and magnetic resonance imaging (MRI) of her brain and spine were normal. She was given a diagnosis of multiple sclerosis (MS) and commenced on vitamin B12 replacement. Three years later, her case was reviewed by the neurology service. She had experienced ongoing sensory disturbances, urinary dysfunction and episodic visual disturbances, consisting of blurred vision, particularly in her right eye, which would last for hours. She also experienced episodes of loss of strength of her right arm and a sensation of dragging her legs. Relevant past medical history included coeliac disease. Examination was normal. Investigations showed prolonged VERs, initially only on the right then bilateral. Somatosensory evoked potentials showed defective conduction in both lower limbs. MRI brain and spine were repeated and were normal. Oligoclonal bands in the CSF were normal. Autoimmune screen was negative. B12 and folate levels, thyroid function tests and syphilis serology were all negative. Tests for aquaporin-4 antibodies were performed twice using a cell based assay with aquaporin-4 M23 isoform and were positive. The titre was three out of four. Given her worsening VERs, with both being greater than 150 ms, her ongoing symptoms and positive aquaporin-4 antibodies, she was commenced on azathioprine. We believe that this patient’s symptoms are due to neuromyelitis optica (NMO). Therapy was initiated due to her prolonged VERs and our concerns regarding future functional visual deterioration. The patient was counseled with regard to the side effects of azathioprine but was very keen herself to commence therapy. Subjectively she feels better on treatment but there has been no change electrophysiologically. We believe that this patient is part of the evolving spectrum of NMO due to her clinical history, prolonged VERs, co-existent autoimmune disease and strongly positive aquaporin-4 antibodies. NMO is an inflammatory, demyelinating syndrome of the central nervous system with predominance of optic nerve and spinal cord involvement [1]. Aquaporin-4 antibodies were first described in 2004 [2]. The sensitivity of the aquaporin-4 antibody cell based assay ranges from 85 to 91% and the specificity is 100% [3, 4]. This patient’s symptoms were mild and her neurological examination was normal. Her symptoms were suggestive of mild transient optic neuritis and myelitis. Although her imaging has been normal thus far, it is possible that her disease may represent a milder phenotype of NMO and any radiological abnormalities present at the time of symptoms could reverse quickly leaving no appreciable abnormalities. The neurophysiological testing and the aquaporin-4 antibodies aided greatly in reaching a diagnosis in this patient and facilitating therapeutic decisions. Given the sensitivity P. H. McNamara (&) 32 Albert College Avenue, Glasnevin, Dublin 9, Ireland e-mail: pmcnamara2004@hotmail.com

Ratchford et al.1 reported a patient with fingolimod-related varicella encephalitis and vasculopathy. The patient's baseline mobility was wheelchair-bound, which means that his Expanded Disability Status Scale (EDSS) score2 was at least 7.0. This suggests that he was no longer in the inflammatory stage of multiple sclerosis (MS) and had secondary progressive MS (SPMS). It is unclear whether the patient's condition met criteria for natalizumab but—at a minimum—the condition must have progressed while on natalizumab. There is neither licensing support nor data from pivotal trials for efficacy of this drug in patients with SPMS.3 The evidence supporting the extension of natalizumab beyond the standard 24 months is also lacking. Fingolimod is licensed for patients with active relapsing-remitting MS but Ratchford et al. stated that this patient was clinically stable. This case highlights an interesting and serious consequence of starting therapy with fingolimod, but the evidence for starting and continuing treatment with this medication—and indeed natalizumab—is lacking in this patient group. This case report also emphasizes the need for evidence-based care, which is safer and more cost-effective.

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.