Acute symptomatic seizures in patients with recurrent ischemic stroke: A multicentric study.

OBJECTIVE: Epileptic seizures occur frequently after stroke due to changes in brain function and structure, and up to around 10% of stroke patients experience stroke recurrence in the first year. We aimed to establish the risk of acute symptomatic seizures in patients with recurrent stroke. METHODS: Retrospective cohort study including consecutive admissions to a Stroke Unit due to acute ischemic stroke, during a 5-year period. Additional inclusion of patients admitted to two centers in different countries to corroborate findings (confirmatory cohort). We aimed to compare acute symptomatic seizure incidence in patients with and without previous stroke. Patients with history of epilepsy were excluded. Logistic regression modeling was performed to identify predictors in middle cerebral artery (MCA) stroke. RESULTS: We included 1473 patients (1085 with MCA stroke), of which 117 had a recurrent ischemic stroke (84 with MCA stroke). Patients with recurrent stroke had a seizure risk during hospital stay similar to that of patients with a first-ever stroke (5.1% vs. 4.5%, OR 1.15, 95% CI .48-2.71, p = .75). Risk of acute symptomatic seizures was also similar (5.0% vs. 4.1, OR 1.22, 95% CI .29-5.27, p = .78). Older age, female sex, and hemorrhagic transformation were predictors of seizures in patients with a first MCA ischemic stroke, but not in recurrent stroke patients. Electrographic characteristics were similar between the two groups in patients who had an electroencephalogram (46 with first stroke, 5 with recurrent stroke). The low rate of seizures (1.5%) in the confirmatory cohort (n = 198) precluded full comparison with the initial cohort. Nevertheless, the rate of seizures was not higher in stroke recurrence. SIGNIFICANCE: History of previous stroke was not associated with an increased risk of acute symptomatic seizures during hospital stay. Larger, prospective studies, with prospective electrophysiological evaluation, are needed to explore the impact of stroke recurrence on seizure risk.

Study of seasonality of attacks in MOG antibody-associated disease.

BACKGROUND: Seasonal variation in attacks of acute disseminated encephalomyelitis (ADEM1) is reported in some studies. Myelin oligodendrocyte glycoprotein (MOG) antibodies are found in up to 50 % of ADEM cases. Despite this, there has been no adequately powered study of seasonality in MOG antibody-associated disease (MOGAD). We sought to determine whether there was an effect of season on incidence of total attacks and onset attacks of MOGAD. METHODS: We searched the large national Oxford-based NMO Service database to identify attacks of MOGAD occurring between 2010 and 2021. Month of each attack was extracted and Edwards' test of seasonal variation was applied to determine whether there was a seasonal effect on total attacks and onset attacks. RESULTS: Neither incidence of total attacks nor incidence of onset attacks varied significantly by month. CONCLUSION: There is no evidence of seasonal fluctuations in the incidence of MOGAD attacks in the UK.

A study of referral bias in NMOSD and MOGAD cohorts.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are rare disorders often seen in highly specialized services or tertiary centres. We aimed to assess if cohort characteristics depend on the origin of the referral catchment areas serviced by our centre (i.e. local, regional or national). METHODS: Retrospective cohort study using a national referral service database including local (Oxfordshire), regional (Oxfordshire and neighbouring counties), and national patients. We included patients with the diagnosis of NMOSD, seronegative NMOSD or MOGAD, followed at the Oxford Neuromyelitis Optica Service. RESULTS: We included 720 patients (331 with MOGAD, 333 with aquaporin-4 antibody (AQP4)-NMOSD, and 56 with seronegative NMOSD. The distribution of diagnoses was similar across referral cohorts. There were no significant differences in the proportion of pediatric onset patients, sex, or onset phenotype; more White AQP4-NMOSD patients were present in the local than in the national cohort (81 % vs 52 %). Despite no differences in follow-up time, more relapsing MOGAD disease was present in the national than in the local cohort (42.9 % vs. 24 %, p = 0.029). CONCLUSION: This is the first study assessing the impact of potential referral bias in cohorts of NMOSD or MOGAD. The racial difference in the AQP4-NMOSD cohorts likely reflects the variation in the population demographics rather than a referral bias. The over representation of relapsing MOGAD patients in the national cohort probably is a true referral bias and highlights the need to analyze incident cohorts when describing disease course and prognosis. It seems reasonable therefore to compare MOGAD and NMOSD patients seen withing specialised centres to general neurology services, provided both use similar antibody assays.

Comorbid autoimmune disorders in people with multiple sclerosis: A retrospective cohort study.

Most autoimmune disorders, including multiple sclerosis (MS), are influenced by shared genetic and environmental factors. We conducted a cohort study of people with MS to calculate the frequency of comorbid autoimmune disorders and characterize this cohort. Autoimmune diseases were present in 30 (8.6%) of 349 patients. The most prevalent diagnoses were autoimmune thyroiditis, type 1 diabetes mellitus, psoriasis, and inflammatory bowel disease. We found no association with demographic or clinical factors. In our cohort, autoimmune disorders were not uncommon. Identifying such comorbidities in people with MS can be determinant for understanding disease mechanisms, treatment decisions and disease management.

Online information search by people with Multiple Sclerosis: A systematic review.

BACKGROUND: People with Multiple Sclerosis (pwMS) search for information online about various aspects of living with their disease, but details about patterns of searching and outcomes are unclear. This means that opportunities to leverage online resources to support pwMS, and to enhance shared decision making, may be missed. We aimed to do a systematic review of the literature on digital information searching by pwMS. METHODS: We performed a systematic search for studies assessing online information seeking of pwMS in MEDLINE and JSTOR databases. Studies were screened and selected by two investigators. All study designs were included, risk of bias was assessed using the Critical Appraisal Skills Programme qualitative checklist. Reports were assessed for the proportion of patients searching information online about MS, type of information sought, online tools used by patients, perceived quality of the information acquired, and impact of online searching in pwMS. RESULTS: We identified 5 studies, including 10,090 patients. Most pwMS search for information online (53.8-82 %), which they rarely discuss with physicians. The most common topics are treatment, general disease information, symptoms, lifestyle recommendations, prognosis, and coping strategies. Patients that are younger, have a shorter disease duration, primary progressive MS, and during periods of disease worsening, are more likely to use online resources. Online information is perceived as low quality by pwMS. CONCLUSIONS: Online information search is prevalent among pwMS. Despite concerns with the quality of the available information, only a minority of pwMS will discuss the information found with their physician. These findings highlight the importance of developing and providing quality online information resources for pwMS.

The effect of smoking on MRI lesion resolution in NMOSD-AQP4 and MOGAD.

BACKGROUND: The effect of smoking on the resolution of magnetic resonance imaging (MRI) lesions in patients with neuromyelitis optica spectrum disorders with aquaporin-4 positive antibody (NMOSD-AQP4) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has not been studied before. OBJECTIVE: We aimed to determine the effect of smoking on lesion resolution in MRI and assess its correlation with clinical recovery after a relapse. METHODS: We conducted a cohort study including NMOSD-AQP4 and MOGAD patients with acute and follow-up MRI scans. We collected demographic, clinical, imaging and smoking data. Logistic regression models were fitted to predict the effect of smoking on lesion resolution and to assess whether clinical recovery was associated with MRI lesion resolution. RESULTS: A total of 105 patients were included (57 with NMOSD-AQP4 and 48 with MOGAD). Current and past smoking was associated with a higher risk of persistent lesions in NMOSD-AQP4 and MOGAD (risk ratio (RR) = 3.4, 95% confidence interval (CI) = 2.5-4.7, p < 0.001). Additionally, the presence of lesion resolution was associated with better clinical recovery (RR = 1.9, 95% CI = 1.7-2.2, p < 0.001). CONCLUSION: Smoking is associated with worse MRI lesion resolution in patients with NMOSD-AQP4 and MOGAD, and lesion resolution correlates with clinical recovery. Our findings suggest a detrimental effect of smoking in inflammatory central nervous system (CNS) diseases.

Longitudinally extensive transverse myelitis with anti-myelin oligodendrocyte glycoprotein antibodies following SARS-CoV-2 infection.

We report the case of a patient with symptoms of myelopathy following acute SARS-CoV-2 infection. MRI documented a longitudinally extensive transverse myelitis and further investigation was unremarkable with the exception of positivity for MOG-IgG in serum. This report extends the spectrum of post-COVID-19 neurological syndromes, and documents a very significant improvement to long-term oral corticosteroid therapy in this setting. Further prospective studies are needed to establish the risk of recurrence in this subset of patients.

Neurology of the acute hepatic porphyrias.

Porphyrias are a set of rare inherited metabolic disorders, each of them representing a defect in one of the eight enzymes in the haem biosynthetic pathway resulting in the accumulation of organic compounds called porphyrins. Acute hepatic porphyrias (AHP) are those in which the enzyme deficiency occurs in the liver, of which acute intermittent porphyria is by far the most common subtype. Neurology of the AHP is still challenging in practice, and patients rarely receive the correct diagnosis early in the disease course. For AHP, which primarily affects the central and peripheral nervous system, the cause of symptoms seems to be the increased production of neurotoxic precursors, in particular delta-aminolaevulinic acid and porphobilinogen. Neurological complications usually result from severe episodes of acute attacks. The neurologic hallmark of porphyrias is an acute predominantly motor axonal neuropathy resembling a Guillain-Barré syndrome that generally occurs after the onset of other clinical features such as abdominal pain and central nervous system manifestations. Neuropsychiatric syndromes, seizures, encephalopathy, and cerebrovascular disorders are among the possible central nervous system presentations. Therapeutic approach to AHP is divided into management and prophylaxis of an acute attack, including long standing options such as intravenous hematin and new therapeutic agents such as givosiran.

Neurologic Manifestations of the Antiphospholipid Syndrome - an Update.

PURPOSE OF REVIEW: In recent years, the spectrum of neurological manifestations of antiphospholipid syndrome (APS) has been growing. We provide a critical review of the literature with special emphasis on presentation, proposed mechanisms of disease, and treatment of neurological involvement in APS. RECENT FINDINGS: Although stroke is the most common cause of neurological manifestations in patients with APS, other neurological disorders have been increasingly associated with the disease, including cognitive dysfunction, headache, and epilepsy. Direct oral anticoagulants have failed to show non-inferiority compared to vitamin K antagonists for the prevention of major thrombotic events. Antiphospholipid antibodies are often found in patients with acute COVID-19 but clear evidence supporting an association between these antibodies and the risk of thrombotic events, including stroke and cerebral venous thrombosis, is still lacking. APS patients may present with several distinct neurological manifestations. New criteria will facilitate the classification of patients presenting with increasingly recognized non-criteria neurological manifestations.

Herpes simplex virus 2 vasculitis as cause of ischemic stroke in a young immunocompromised patient.

Herpes simplex virus 2 (HSV-2) is a very rare cause of central nervous system (CNS) infections. We report a case of a young woman with a left middle cerebral artery (MCA) ischemic stroke. The patient had history of HIV-1 infection, with periods of therapeutic non-compliance. Initial computed tomography (CT) imaging studies showed stenosis of the M1 segment of the left MCA, and magnetic resonance imaging (MRI) confirmed infarction of the MCA territory. Serial transcranial Doppler ultrasound revealed progressive occlusion of the MCA and stenosis of the left anterior cerebral artery. Systemic investigation for other causes of stroke was normal. Lumbar puncture revealed a mildly inflammatory cerebrospinal fluid, and HSV-2 DNA was identified by PCR, with a positive viral load in favor of active replication. No other viral or microbiological infections were identified. MRI angiography confirmed a vasculitic process involving the left carotid artery, and a HSV-2 vasculitis diagnosis was assumed. The patient started acyclovir with improvement of clinical features and imaging abnormalities. In the HIV-infected patient, stroke is a multifactorial common cause of morbidity. The physician should take into account a broad differential diagnosis including rare causes and atypical presentations of common etiologies, including HSV-1 and HSV-2 CNS infection.

Nocebo response in Parkinson's disease: A systematic review and meta-analysis.

OBJECTIVE: To estimate the magnitude of the nocebo response in Parkinson's disease and explore possible associations with study characteristics. METHODS: Databases were searched up to February 2017. Placebo-controlled, parallel-group randomized controlled trials investigating pharmacological interventions in people with Parkinson's disease were included. Data were derived from the last measured within-group response in the placebo and intervention arms of randomized controlled trials, after independent extraction. A random-effects model was used to pool study data. The main outcome was the nocebo response, measured as the proportion of placebo-treated participants experiencing any adverse events (AEs). We also measured the proportion of patients with serious AEs (SAEs), and the rates of study dropouts (including due to AEs) and death. PROSPERO registration number is CRD42017070471. RESULTS: We included 236 randomized controlled trials, with a combined population of 17,381 participants allocated to placebo. The nocebo response was 56.0% (95% CI, 51.7%-60.4%; 148 trials; I2 = 98%). SAEs were reported in 4.0% (95% CI, 3.4%-4.6%, 157 trials; I2 = 73%) of placebo-treated patients, dropouts in 14.0% (95% CI, 12.5%-15.5%, 225 trials; I2 = 91%), dropouts due to AEs in 5.7% (95% CI, 5.1%-6.4%, 219 trials; I2 = 73%). Deaths occurred in 0.6% (95% CI, 0.5%-0.7%, 227 trials; I2 = 0%). Similar proportions were identified in patients in intervention arms. CONCLUSIONS: The magnitude of the nocebo response in parallel-designed randomized controlled trials in Parkinson's disease is substantial and should be considered in the interpretation of safety results and in the design and interpretation of future clinical trials.

Direct Gaze Partially Overcomes Hemispatial Neglect and Captures Spatial Attention.

Direct gaze has been shown to be a particularly important social cue, being preferentially processed even when unconsciously perceived. Results from several visual search tasks further suggest that direct gaze modulates attention, showing a faster orientation to faces perceived as looking toward us. The present study aimed to analyze putative modulation of spatial attention by eye gaze direction in patients with unilateral neglect. Eight right hemisphere stroke patients with neglect performed a target cancelation paradigm. Patients were instructed to cross all open-eyed pictures amidst closed eyed distractors. Target images were either in direct or averted gaze. Participants performed significantly better when observing targets with direct gaze supporting the hypothesis that this gaze direction captures attention. These findings further suggest that perception of direct gaze is able to diminish the visuospatial impairment seen in neglect patients.

Underneath the academic curiosity.

As a medical student, I have now almost 6 years of academic studies and clinical interaction with numerous patients, though sometimes brief and superficial. I have found that sometimes it is truly hard to grasp how humane a person is behind their sickness. Fortunately, I have been hitherto able to avoid the almost natural desensitization our degree imposes upon us, either through my own process of thought or through a kind warning of some of "my" patients. Having been particularly thrown aback by the keen eye of a patient I had the opportunity to meet in an Oncology ward, I realized that I had much more to consider when studying a clinical case and that rarely a cancer (or a disease whatever it may be) is but a cancer. In fact, a disease needs a patient to be diagnosed upon and that patient has most often a life besides their disease.