Eva Kumlien

Background and Purpose: Biomarkers for neuronal damage have been shown to be elevated during the acute phase of COVID‐19 in plasma and cerebrospinal fluid (CSF) of patients with neurological symptoms. Little is known about the temporal dynamics of these biomarkers and their pathophysiological relationship to neurocognitive post‐COVID condition (neuro‐PCC). Our aim was to conduct a follow‐up of clinical symptoms and biomarkers of patients with neurological symptoms in the acute phase of COVID‐19. Methods: Follow‐up was conducted > 4 months after onset of COVID‐19 symptoms. Twenty‐eight patients were included and underwent neurological examination, neuropsychiatric and cognitive assessments, and serological testing. Eight patients underwent lumbar puncture. Neurofilament light (NfL), total tau (T‐tau), glial fibrillary acidic protein (GFAP), and neuronal antibodies were analyzed in serum or plasma and CSF. Results: New‐onset symptoms post‐COVID were reported in 82%. Neurological examination revealed abnormalities in 32% of patients. GFAP and T‐tau had normalized in CSF in all patients. However, one patient still showed elevated NfL chain levels in CSF, while two patients had elevated NfL in plasma. New‐onset neuronal antibodies in serum were found in 5/27 (19%) and in one patient in CSF. No correlation was found between biomarker levels during acute COVID‐19 disease and subsequent neurological symptoms or examination findings at follow‐up. Conclusion: Several patients reported new‐onset neurological and cognitive symptoms, despite the absence of evidence of ongoing neuronal damage. Additionally, the presence of newly developed autoantibodies was detected in several patients, potentially signaling the emergence of post‐COVID autoimmunity.

Background We investigated all-cause and epilepsy-related mortality in patients operated with resective epilepsy surgery and in non-operated patients with drug-resistant epilepsy. Our hypothesis was that patients who proceed to surgery have lower mortality over time compared with non-operated patients. Method Data from 1329 adults and children from the Swedish National Epilepsy Surgery Register and 666 patients with drug-resistant epilepsy who had undergone presurgical work-up but not been operated were analysed. The operated patients had follow-ups between 2 and 20 years. We used the Swedish Cause of Death Register to identify deaths. Autopsy reports were collected for patients with suspected sudden unexpected death in epilepsy (SUDEP). Kaplan-Meier and Cox regression analyses were performed to identify predictors for mortality and SUDEP. Results SUDEP accounted for 30% of all deaths. Surgery was associated with lower all-cause mortality (HR 0.7, 95% CI 0.5 to 0.9), also when adjusted for age, sex and tonic–clonic seizures at inclusion. The benefit of surgery seemed to persist and possibly even increase after 15 years of follow-up. Risk factors of mortality for operated patients were persisting seizures and living alone. Of the operated patients, 37% had seizures, and these had a higher risk of mortality (HR 2.1, 95% CI 1.4 to 3.0) and SUDEP (HR 3.5, 95% CI 1.7 to 7.3) compared with patients with seizure freedom at last follow-up. Conclusions In this large population-based epilepsy surgery cohort, operated patients had a lower all-cause mortality compared with non-operated patients with drug-resistant epilepsy. Seizure freedom was the most important beneficial factor for both all-cause mortality and SUDEP among operated patients.

Background and purpose: COVID‐19 is associated with multiple neurological manifestations. The clinical presentation, trajectory, and treatment response for three cases of myoclonus during COVID‐19 infection, with no previous neurological disease, are decsribed.Metods: Analysis of cerebrospinal fluid from the cases using indirect immunohistochemistry.Results: Antibodies against rodent brain tissue, and similarities in staining patterns were observed, indicating the presence of antineuronal immunoglobulin G autoantibodies targeting astrocytes in the hippocampus.Conclusion: Our results demontrate cerebrospinal fluid antineuronal antibodies indicating an an autoimmune involvment in the pathogenesis in COVID‐19 associated myoclonus.

Background and aims To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19). Methods We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL. Results We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13–3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively. Conclusions Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.

Clinical practice guidelines (CPGs) are statements that provide evidence‐based recommendations aimed at optimizing patient care. However, many other documents are often published as “guidelines” when they are not; these documents, although also important in clinical practice, are usually not systematically produced following rigorous processes linking the evidence to the recommendations. Specifically, the International League Against Epilepsy (ILAE) guideline development toolkit aims to ensure that high‐quality CPGs are developed to fill knowledge gaps and optimize the management of epilepsy. In addition to adhering to key methodological processes, guideline developers need to consider that effective CPGs should lead to improvements in clinical processes of care and health care outcomes. This requires monitoring the effectiveness of epilepsy‐related CPGs and interventions to remove the barriers to epilepsy CPG implementation. This article provides an overview of what distinguishes quality CPGs from other documents and discusses their benefits and limitations. We summarize the recently revised ILAE CPG development process and elaborate on the barriers and facilitators to guideline dissemination, implementation, and adaptation.

Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBF_ASL) and ¹⁵O-water positron emission tomography (PET) (CBF_PET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic ¹⁵O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). ¹⁵O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBF_ASL and CBF_PET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = −15 mL/100 g/min, lower and upper limits of agreements = −16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBF_ASL and CBF_PET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with ¹⁵O-water PET.

SUMMARY: Acute malignant catatonia with autonomic instability developed in a previously healthy man with PCR-verified SARS-CoV-2. CT and MRI were normal, EEG showed slowing and cerebrospinal fluid showed a subtle indication of inflammation. There were no signs of pathology in other organs. ¹⁸ F-FDG-PET conveyed high bilateral uptake in the striatum. While commercial tests were negative, immunohistochemical staining of mouse brain revealed anti-neuronal IgG antibodies against neuronal targets in the hippocampus, thalamus, striatum and cortex. Early treatment with plasmapheresis and corticosteroid reversed disease progression and may have prevented large-scale neurological damage. We are not aware of other types of encephalitis with such distinct pyramidal tract symptoms and raise the possibility that this may be a novel form of autoimmune encephalitis induced by infection with SARS-CoV-2.

Introduction: Recently, several epidemiological studies have demonstrated that epilepsy develops after approximately 10% of all cerebrovascular lesions. With an aging population, poststroke epilepsy is likely to be of increasing relevance to neurologists and more knowledge on the condition is needed. Patients with poststroke epilepsy are likely to differ from other epilepsy patient populations regarding age, side‐effect tolerability, comorbidities, and life expectancy, all of which are important aspects when counselling newly diagnosed patients to make informed treatment decisions.Method: We have here performed a nested case–control study on 36 patients with poststroke epilepsy and 55 controls that suffered stroke but did not develop epilepsy. The average follow‐up time was between 3 and 4 years.Results: In our material, two‐thirds of patients achieved seizure freedom and 25% experienced a prolonged seizure (status epilepticus) during the follow‐up period. Cases consumed more health care following their stroke, but did not suffer more traumatic injuries. Interestingly, the mortality among cases and controls did not differ significantly. This observation needs to be confirmed in larger prospective studies, but indicate that poststroke epilepsy might not infer additional mortality in this patient group with considerable comorbidities.Conclusions: The observations presented can be of value in the counselling of patients, reducing the psychosocial impact of the diagnosis, and planning of future research on poststroke epilepsy.