Association of Mortality and Risk of Epilepsy With Type of Acute Symptomatic Seizure After Ischemic Stroke and an Updated Prognostic Model.

Importance: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk. Objective: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures. Design, Setting, and Participants: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022. Exposures: Type of acute symptomatic seizure. Main Outcomes and Measures: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke). Results: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy. Conclusions and Relevance: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up.

Seizures after Ischemic Stroke: A Matched Multicenter Study.

OBJECTIVE: The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. METHODS: We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. RESULTS: In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large-artery atherosclerosis. Strokes caused by small-vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post-stroke epilepsy. Risk factors for post-stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large-artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post-stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post-stroke epilepsy or the risk of acute symptomatic seizures. INTERPRETATION: Post-stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post-stroke epilepsy. ANN NEUROL 2021;90:808-820.

Development and Validation of a Prognostic Model of Swallowing Recovery and Enteral Tube Feeding After Ischemic Stroke.

Importance: Predicting the duration of poststroke dysphagia is important to guide therapeutic decisions. Guidelines recommend nasogastric tube (NGT) feeding if swallowing impairment persists for 7 days or longer and percutaneous endoscopic gastrostomy (PEG) placement if dysphagia does not recover within 30 days, but, to our knowledge, a systematic prediction method does not exist. Objective: To develop and validate a prognostic model predicting swallowing recovery and the need for enteral tube feeding. Design, Setting, and Participants: We enrolled participants with consecutive admissions for acute ischemic stroke and initially severe dysphagia in a prospective single-center derivation (2011-2014) and a multicenter validation (July 2015-March 2018) cohort study in 5 tertiary stroke referral centers in Switzerland. Exposures: Severely impaired oral intake at admission (Functional Oral Intake Scale score <5). Main Outcomes and Measures: Recovery of oral intake (primary end point, Functional Oral Intake Scale ≥5) or return to prestroke diet (secondary end point) measured 7 (indication for NGT feeding) and 30 (indication for PEG feeding) days after stroke. Results: In total, 279 participants (131 women [47.0%]; median age, 77 years [interquartile range, 67-84 years]) were enrolled (153 [54.8%] in the derivation study; 126 [45.2%] in the validation cohort). Overall, 64% (95% CI, 59-71) participants failed to recover functional oral intake within 7 days and 30% (95% CI, 24-37) within 30 days. Prolonged swallowing recovery was independently associated with poor outcomes after stroke. The final prognostic model, the Predictive Swallowing Score, included 5 variables: age, stroke severity on admission, lesion location, initial risk of aspiration, and initial impairment of oral intake. Predictive Swallowing Score prediction estimates ranged from 5% (score, 0) to 96% (score, 10) for a persistent impairment of oral intake on day 7 and from 2% to 62% on day 30. Model performance in the validation cohort showed a discrimination (C statistic) of 0.84 (95% CI, 0.76-0.91; P < .001) for predicting the recovery of oral intake on day 7 and 0.77 (95% CI, 0.67-0.87; P < .001) on day 30, and a discrimination for a return to prestroke diet of 0.94 (day 7; 95% CI, 0.87-1.00; P < .001) and 0.71 (day 30; 95% CI, 0.61-0.82; P < .001). Calibration plots showed high agreement between the predicted and observed outcomes. Conclusions and Relevance: The Predictive Swallowing Score, available as a smartphone application, is an easily applied prognostic instrument that reliably predicts swallowing recovery. It will support decision making for NGT or PEG insertion after ischemic stroke and is a step toward personalized medicine.

Prediction of late seizures after ischaemic stroke with a novel prognostic model (the SeLECT score): a multivariable prediction model development and validation study.

BACKGROUND: Stroke is one of the leading causes of acquired epilepsy in adults. An instrument to predict whether people are at high risk of developing post-stroke seizures is not available. We aimed to develop and validate a prognostic model of late (>7 days) seizures after ischaemic stroke. METHODS: In this multivariable prediction model development and validation study, we developed the SeLECT score based on five clinical predictors in 1200 participants who had an ischaemic stroke in Switzerland using backward elimination of a multivariable Cox proportional hazards model. We externally validated this score in 1169 participants from three independent international cohorts in Austria, Germany, and Italy, and assessed its performance with the concordance statistic and calibration plots. FINDINGS: Data were complete for 99·2% of the predictors (99·2% for Switzerland, 100% for Austria, 97% for Germany, and 99·7% for Italy) and 100% of the outcome parameters. Overall, the risk of late seizures was 4% (95% CI 4-5) 1 year after stroke and 8% (6-9) 5 years after stroke. The final model included five variables and was named SeLECT on the basis of the first letters of the included parameters (severity of stroke, large-artery atherosclerotic aetiology, early seizures, cortical involvement, and territory of middle cerebral artery involvement). The lowest SeLECT value (0 points) was associated with a 0·7% (95% CI 0·4-1·0) risk of late seizures within 1 year after stroke (1·3% [95% CI 0·7-1·8] within 5 years), whereas the highest value (9 points) predicted a 63% (42-77) risk of late seizures within 1 year (83% [62-93] within 5 years). The model had an overall concordance statistic of 0·77 (95% CI 0·71-0·82) in the validation cohorts. Calibration plots indicated high agreement of predicted and observed outcomes. INTERPRETATION: This easily applied instrument was shown to be a good predictor of the risk of late seizures after stroke in three external validation cohorts and is freely available as a smartphone app. The SeLECT score has the potential to identify individuals at high risk of seizures and is a step towards more personalised medicine. It can inform the selection of an enriched population for antiepileptogenic treatment trials and will guide the recruitment for biomarker studies of epileptogenesis. FUNDING: None.

Heart rate variability decreases after 3 months of sustained treatment with fingolimod.

The objective is to prospectively investigate short- and mid-term changes of heart rate variability (HRV) in patients with relapsing-remitting multiple sclerosis (RRMS), being started on fingolimod. In this prospective clinical trial, patient (n = 33) with RRMS starting treatment with fingolimod underwent a time-domain-based analysis of HRV (breathing at rest, deep breath, and in response to the Valsalva maneuver) shortly before, 4.5 h and 3 months after first intake. Blood pressure changes after the Valsalva maneuver were used as a marker of the sympathetic noradrenergic system. We used a non-invasive continuous beat-to-beat heart rate and blood pressure monitoring. In addition, the Fatigue Severity Scale and the refined and abbreviated Composite Autonomic Symptom Score were applied. Significant changes in HRV in RRMS patients, following treatment with fingolimod, were detected. After an initial increase in HRV, measured 4.5 h after the first intake of fingolimod, a substantial decrease in HRV occurred within 3 months on continuous treatment. There is a growing body of evidence for short-term cardiovascular side effects in continuous treatment with fingolimod, driven by the ANS. The mechanisms and the clinical relevance of the observed changes in HRV need further evaluation, especially in longer and larger prospective studies.

Unilateral tongue myokymia - A rare topodiagnostic sign of different clinical conditions.

Myokymia of the tongue is a very rare clinical condition and is much less common than facial or focal myokymia of the limbs. Radiation-induced delayed nerve damage is a well-known cause of myokymia, but other etiologies i.e. tumor recurrence should be considered as a differential diagnosis. We describe a case series of neurophysiologically proven unilateral tongue myokymia, which arose in two patients after radiotherapy of the neck/head and in one patient due to a space occupying meningioma of the cerebrospinal passage affecting the hypoglossal nerve. With this case series and a review of the literature we aim to raise clinical suspicion of tongue myokymia and highlight the clinical and electromyographic impact of myokymia in the diagnosis of malignancies and treatment-associated lesions of the hypoglossal nerve.

Nerve Ultrasound as a Decisive Tool in Nonsystemic Vasculitic Neuropathy: A Case Report.

INTRODUCTION: The additional value of peripheral nerve ultrasound in acquired immune-mediated neuropathies has recently been reported. Its impact in vasculitic neuropathy is yet to be defined. We report electrophysiological and nerve ultrasound studies in a patient with nonsystemic vasculitic neuropathy at first diagnosis and in response to immunosuppression. CASE REPORT: A 44-year-old female presented with painful neuropathy and weakness of the intrinsic hand muscles. Electrodiagnostic studies revealed severe axonal neuropathy of the nerves of the left arm. On nerve ultrasound, massive and patchy swelling of these nerves was detected. Clinical, laboratory, and radiological evidence of nonneuromuscular involvement and systemic vasculitic diseases was absent. Hence, nonsystemic vasculitic neuropathy was diagnosed without the possibility of histological verification. After 6 months of systemic immunosuppression with steroids and cyclophosphamide, clinical symptoms improved in parallel with neurosonography. In contrast, electrophysiological studies remained pathological despite clinical improvement. CONCLUSIONS: Neurosonography studies in nonsystemic vasculitic neuropathy are rare but might be an ancillary technique to guide noninvasive diagnosis and therapeutic monitoring. Morphological analysis of nerves and changes in response to treatment could be well visualized. Additionally, neurosonography might be useful to target nerve biopsy.

[Anticonvulsive Therapy after the First Unprovoked Seizure ­ Pros and Cons]. / Antikonvulsive Therapie nach dem ersten epileptischen Anfall - pro und contra.

A first seizure is a critical life time event with severe consequences. A very thorough work-up is needed to find out the cause of the seizure and to number the risk of recurrence. Reasons for an anticonvulsive therapy are a pathologic EEG, a pathologic neurologic examination, the proof of a structural lesion, focal seizure onset or seizure onset while sleeping or classification as an epilepsy syndrome with high recurrence risk like juvenile myoclonic epilepsy or juvenile absence epilepsy. Psychological and social aspects like the patients or relatives fear of a further seizure, the risk of injury and occupational and recreational aspects must be considered as well. Reasons against an anticonvulsive therapy are mainly related to adverse effects like gain of weight and osteoporosis.

Spinal Cord Disorders.

BACKGROUND: The spinal cord is the main pathway for information, connecting the brain and the peripheral nervous system. Any disorder that results in spinal cord dysfunction will have a dramatic impact on the patient's quality of life. This review focusses on myelopathy, specifically, on the acute and subacute clinical presentations and the inflammatory and vascular etiology of this widespread disorder. SUMMARY: Myelopathy following spinal cord injury is a generic term referring to a lesion that affects the spinal cord following traumatic injury, or autoimmune, infectious, neoplastic, vascular and hereditary degenerative diseases. Depending on the patient's medical history, the underlying clinical syndrome and the temporal course of the manifestation, the clinician must account for a wide range of possible differential diagnoses. KEY MESSAGES: Spinal cord disorders pose a tremendous challenge for the clinician, as they show great variability in clinical presentation but can have potentially devastating sequelae. The acute and sometimes urgent nature of therapeutic management is highly dependent on the underlying disorder, often necessitating a combination of approaches including surgical or conservative therapies (including immunomodulatory therapy) and an interdisciplinary approach to achieve the best outcomes.

De novo status epilepticus with isolated aphasia.

BACKGROUND: Sudden onset of aphasia is usually due to stroke. Rapid diagnostic workup is necessary if reperfusion therapy is considered. Ictal aphasia is a rare condition but has to be excluded. Perfusion imaging may differentiate acute ischemia from other causes. In dubious cases, EEG is required but is time-consuming and laborious. We report a case where we considered de novo status epilepticus as a cause of aphasia without any lesion even at follow-up. A 62-year-old right-handed woman presented to the emergency department after nurses found her aphasic. She had undergone operative treatment of varicosis 3 days earlier. Apart from hypertension and obesity, no cardiovascular risk factors and no intake of medication other than paracetamol were reported. Neurological examination revealed global aphasia and right pronation in the upper extremity position test. Computed tomography with angiography and perfusion showed no abnormalities. Electroencephalogram performed after the CT scan showed left-sided slowing with high-voltage rhythmic 2/s delta waves but no clear ictal pattern. Intravenous lorazepam did improve EEG slightly, while aphasia did not change. Lumbar puncture was performed which likely excluded encephalitis. Magnetic resonance imaging showed cortical pathological diffusion imaging (restriction) and cortical hyperperfusion in the left parietal region. Intravenous anticonvulsant therapy under continuous EEG resolved neurological symptoms. The patient was kept on anticonvulsant therapy. Magnetic resonance imaging after 6 months showed no abnormalities along with no clinical abnormalities. CONCLUSIONS: Magnetic resonance imaging findings were only subtle, and EEG was without clear ictal pattern, so the diagnosis of aphasic status remains with some uncertainty. However, status epilepticus can mimic stroke symptoms and has to be considered in patients with aphasia even when no previous stroke or structural lesions are detectable and EEG shows no epileptic discharges. Epileptic origin is favored when CT or MR imaging reveal no hypoperfusion. In this case, MRI was superior to CT in detecting hyperperfusion. This article is part of a Special Issue entitled "Status Epilepticus".

Risk factors, aetiology and outcome of ischaemic stroke in young adults: the Swiss Young Stroke Study (SYSS).

Ischaemic stroke (IS) in young adults has been increasingly recognized as a serious health condition. Stroke aetiology is different in young adults than in the older population. This study aimed to investigate aetiology and risk factors, and to search for predictors of outcome and recurrence in young IS patients. We conducted a prospective multicentre study of consecutive IS patients aged 16-55 years. Baseline demographic data, risk factors, stroke aetiology including systematic genetic screening for Fabry disease and severity were assessed and related to functional neurological outcome (modified Rankin Scale, mRS), case fatality, employment status, place of residence, and recurrent cerebrovascular events at 3 months. In 624 IS patients (60% men), median age was 46 (IQR 39-51) years and median NIHSS on admission 3 (IQR 1-8). Modifiable vascular risk factors were found in 73%. Stroke aetiology was mostly cardioembolism (32%) and of other defined origin (24%), including cervicocerebral artery dissection (17%). Fabry disease was diagnosed in 2 patients (0.3%). Aetiology remained unknown in 20%. Outcome at 3 months was favourable (mRS 0-1) in 61% and fatal in 2.9%. Stroke severity (p < 0.001) and diabetes mellitus (p = 0.023) predicted unfavourable outcome. Stroke recurrence rate at 3 months was 2.7%. Previous stroke or TIA predicted recurrent cerebrovascular events (p = 0.012). In conclusion, most young adults with IS had modifiable vascular risk factors, emphasizing the importance of prevention strategies. Outcome was unfavourable in more than a third of patients and was associated with initial stroke severity and diabetes mellitus. Previous cerebrovascular events predicted recurrent ones.

Association of cognitive impairment and lesion volumes in multiple sclerosis--a MRI study.

UNLABELLED: Cognitive impairment (CI) can be demonstrated in 40-65% of multiple sclerosis (MS) patients, sometimes starting from the early stages of the disease. The objective of this study was a community-based investigation of FLAIR-hyperintense lesion volumes (LV) and their association with CI in patients with relapsing remitting (RR) MS. The neurocognitive assessment was conducted with the brief cognitive screening instrument, MUSIC. Magnetic resonance imaging (MRI) scans were obtained with a 1.5 Tesla Sigma Magnetom MRI scanner. We conducted a stepwise multiple regression analysis to assess the relative contribution of the main clinical, demographic and MRI-variables in predicting cognitive impairment. We recruited 78 patients with RRMS. The mean MUSIC score was 20.6 ± 5.4. Forty five percent of patients (n = 35, mean score 15.1 ± 3.3) had CI and 55% (n = 43, mean score 24.4 ± 2.5) had no sign of CI. In the correlation analysis of the MUSIC subtests only the interference test correlated negatively with the LV (r = -0.23). Multivariate linear regression analysis using MUSIC as the dependent continuous variable revealed LV and disability severity as independent factors associated with MUSIC (p value of the regression model < 0.001; adjusted R-square = 0.11). The results of the present study suggest an association between white matter damage and CI in MS. We could demonstrate an association between attention difficulties and the LV in MS patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01250665 and NCT01250678.

[Nerve sonography of intraneural ganglia as cause painful peroneal palsies: a case series]. / Nervensonographie intraneuraler Ganglien als Ursache schmerzhafter N.-peronaeus-Paresen: eine Fallserie.

In selected cases acquired peroneal palsy is caused by intraneural ganglia. In contrast to the much more frequent "loco typico" lesion which is caused by external pressure, intraneural ganglia can be treated by microscopic nerve surgery as part of primary treatment strategy. A careful clinical history as well as a profound clinical and electrophysiological examination is required to disclose unusual findings. These are common in non-typical peroneal palsy. In this situation high resolution nerve sonography is a fast and sensitive method to detect intraneural ganglia. We report a case series of three patients with peroneal palsy caused by intraneural ganglia and give a review of the literature.

Rarement la lésion du nerf péronier au niveau de la tête fibulaire suivie par une parésie des muscles innervés par ce nerf est causée par un ganglion appuyant sur les structures nerveuses. En ce cas une intervention chirurgicale peut souvant résondre le problème. Une anamnèse soigneusement menée, l'examen neurologique et des investigations neuromusculaires sont essentielles mais souvent atypiques comparés à la lésion péronière «loco typico¼. L'ultrasonographie à haute résolution est procédée facilement et plus sensible qu'une MRI. Nous allons décrire dans ce papier trois cas de parèsie du nerf péronier pour lesquels la diagnostic final a été posé par ultrasonographie.

Radiation-induced cavernoma after total body irradiation and haematopoietic stem cell transplantation in an adult patient suffering from acute myeloid leukaemia.

Cerebral cavernomas are thin-walled vascular lesions composed of dilated capillary spaces. De novo formation of cavernomas after cerebral radiotherapy has been suspected since 1994. They are mostly seen in children after irradiation of brain tumours. Radiation dose and the developing juvenile brain are predisposing factors causing cavernomas. However, the underlying mechanisms are still far from being understood. In adults, radiation-induced cavernomas (RICs) usually occur 10 years after a high cumulative radiation dosage of >30 Gy. Here, we report a 45-year-old man with new-onset focal epileptic seizures caused by a haemorrhagic lesion noted on cerebral computed tomography scan. Brain MRI showed the typical appearance of a ruptured cavernoma. Of note, a cerebral MRI scan 5 years earlier showed no corresponding lesion. The patient had been treated with haematopoietic stem cell transplantation for acute myeloid leukaemia (AML) 16 years before. As part of this procedure, total body irradiation (TBI) consisting of 12 Gy was administered. According to the data from the literature, the typical delay from irradiation and a former normal brain MRI scan, we assume that our patient suffers from a RIC. To our knowledge, this is the first documented adult AML patient with a RIC treated with TBI. We aim to increase awareness among neurologists for the association of cranial irradiation or TBI and de novo cavernomas in patients suffering from malignant diseases.

Trajectory of fatigue severity in natalizumab treated multiple sclerosis patients.

Fatigue is one of the most debilitating symptoms in multiple sclerosis (MS). The aim of this study was to observe the severity of MS associated fatigue in a community-based sample of natalizumab (ntz) treated patients over one year. In 48 relapsing remitting MS patients (mean age=38.3 years) fatigue was longitudinally measured with the Modified Fatigue Impact Scale (MFIS) at two time points. The primary analysis of differences in MFIS was performed using non-parametric Wilcoxon test for dependent variables. Mean total MFIS Score increased significantly from 32.6±20.9 to 49.1±20.0 over the observation period of 12 months (p<0.001). 83% of patients remained clinically disease activity free (no relapse, no progression in the Expanded Disability Status Scale, EDSS) over the observation period of one year. Age, gender, disease duration, spinal involvement, Gd-enhancement, depressive symptoms and EDSS had no influence on fatigue levels as measured with MFIS. Severity of fatigue symptoms during ntz treatment might increase despite very low disease activity.

Stroke and pregnancy.

Strategies for stroke prevention should take into account the competing risks to mother and fetus. Treatment of acute stroke in pregnant women is still controversial, but not strictly contraindicated. Several case reports have documented successful reperfusion, in addition to satisfactory maternal and fetal outcomes. Aspirin and warfarin are safe in the second and third trimesters. There are no trials of anticoagulation or antiplatelet therapies of stroke prevention in pregnancy.