Status epilepticus management in patients with brain tumors. A cohort study.

PURPOSE: Status epilepticus (SE) represents a neurological emergency with significant morbidity and mortality. SE in patients with primary brain tumors received only limited attention to date; detailed analysis of treatment flow is lacking, especially as compared to other SE causes. This study aims to describe the frequency and treatment flow of tumor-related SE and compare it to other SE etiologies. METHODS: Retrospective cohort study based on an institutional SE registry (SERCH) comprising adult SE (excluding post-anoxic causes), treated between January 2013 and December 2022, comparing SE management, frequency of refractory SE, and clinical outcome, among four patients' groups stratified by SE etiology: Non-neoplastic, Gliomas, Brain metastases, Other brain tumors. RESULTS: We analyzed 961 episodes in 831 patients (Non-neoplastic: 649, Gliomas: 85, Metastases: 77, Other brain tumors: 20). Although tumor-patients presented more often with focal episodes and less consciousness impairment than non-neoplastic patients, administration of benzodiazepines as first-line treatment (>75% across all groups), and utilization of second-line ASM were similar across groups. Treatment adequacy was marginally higher in glioma patients compared to the non-neoplastic population (p: 0.049), while refractory SE was comparable in all groups (p: 0.269). No significant differences in clinical outcomes were observed (mortality: non-neoplastic (89/649, 13.7%), glioma (8/85, 9.4%), metastases (14/77, 18.2%), other tumors (5/20, 25.0%), p: 0.198; non-neoplastic vs. glioma, p: 0.271) CONCLUSION: Tumor-associated SE represents 1/5 of all SE episodes, and is managed similarly to other SE causes. Treatment responsiveness and short-term clinical outcomes also exhibit comparable results.

Relationship between serum neuron-specific enolase and EEG after cardiac arrest: A reappraisal.

OBJECTIVE: Electroencephalogram (EEG) and serum neuron specific enolase (NSE) are frequently used prognosticators after cardiac arrest (CA). This study explored the association between NSE and EEG, considering the role of EEG timing, its background continuity, reactivity, occurrence of epileptiform discharges, and pre-defined malignancy degree. METHODS: Retrospective analysis including 445 consecutive adults from a prospective registry, surviving the first 24 hours after CA and undergoing multimodal evaluation. EEG were interpreted blinded to NSE results. RESULTS: Higher NSE was associated with poor EEG prognosticators, such as increasing malignancy, repetitive epileptiform discharges and lack of background reactivity, independently of EEG timing (including sedation and temperature). When stratified for background continuity, NSE was higher with repetitive epileptiform discharges, except in the case of suppressed EEGs. This relationship showed some variation according to the recording time. CONCLUSIONS: Neuronal injury after CA, reflected by NSE, correlates with several EEG features: increasing EEG malignancy, lack of background reactivity, and presence of repetitive epileptiform discharges. The correlation between epileptiform discharges and NSE is influenced by underlying EEG background and timing. SIGNIFICANCE: This study, describing the complex interplay between serum NSE and epileptiform features, suggests that epileptiform discharges reflect neuronal injury particularly in non-suppressed EEG.

Multimodal Prediction of Favorable Outcome After Cardiac Arrest: A Cohort Study.

OBJECTIVES: Prognostic guidelines after cardiac arrest (CA) focus on unfavorable outcome prediction; favorable outcome prognostication received less attention. Our aim was to identify favorable outcome predictors and combine them into a multimodal model. DESIGN: Retrospective analysis of prospectively collected data (January 2016 to June 2021). SETTING: Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Brigham and Women's Hospital, Boston, MA). PATIENTS: Four hundred ninety-nine consecutive comatose adults admitted after CA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CA variables (initial rhythm, time to return of spontaneous circulation), clinical examination (Full Outline of UnResponsiveness [FOUR] score at 72 hr, early myoclonus), electroencephalography (EEG) (reactivity, continuity, epileptiform features, and prespecified highly malignant patterns), somatosensory-evoked potentials, quantified pupillometry, and serum neuron-specific enolase (NSE) were retrieved. Neurologic outcome was assessed at 3 months using Cerebral Performance Category (CPC); 1 and 2 were considered as favorable outcome. Predictive performance of each variable toward favorable outcomes were calculated, and most discriminant items were combined to obtain a multimodal prognostic score, using multivariable ordinal logistic regression, receiving operator characteristic curves, and cross-validation. Our analysis identified a prognostic score including six modalities (1 point each): 1) early (12-36 hr) EEG not highly malignant, 2) early EEG background reactivity, 3) late (36-72 hr) EEG background reactivity and 4) continuity, 5) peak serum NSE within 48 hours less than or equal to 41 µg/L, and 6) FOUR score greater than or equal to 5 at 72 hours. At greater than or equal to 4 out of 6 points, sensitivity for CPC 1-2 was 97.5% (95% CI, 92.9-99.5%) and accuracy was 77.5% (95% CI, 72.7-81.8%); area under the curve was 0.88 (95% CI, 0.85-0.91). The score showed similar performances in the validation cohort. CONCLUSIONS: This study describes and externally validates a multimodal score, including clinical, EEG and biological items available within 72 hours, showing a high performance in identifying early comatose CA survivors who will reach functional independence at 3 months.

[Neurology: what's new in 2022]. / Neurologie : ce qui a changé en 2022.

The year 2022 was marked by the development of numerous new treatments for refractory myasthenia gravis. The link between epilepsy and cerebrovascular disorder was studied and lamotrigine discovered to be the optimal treatment choice for epilepsy secondary to stroke to prevent mortality on patient of 45 years and older. New randomized study finally demonstrated the utility of thrombectomy in selected patients with basilar artery occlusion. The causal relationship between Epstein-Barr infection and multiple sclerosis has been proved thanks to a large cohort study. A new possibility of subcutaneous continuous levodopa administration gave promising result. Finally, numerous studies confirmed the efficacy and excellent tolerability of anti-CGRP antibodies.

L'année 2022 a été marquée par l'arrivée de nombreux traitements pour la myasthénie réfractaire. Le lien entre l'épilepsie et le risque cérébro-vasculaire a été bien étudié, démontrant que la lamotrigine semble être le meilleur traitement pour prévenir la mortalité chez les patients de 45 ans et plus. De nouvelles études ont enfin pu établir l'utilité de la thrombectomie dans les occlusions basilaires. Le lien entre le virus d'Epstein-Barr et la sclérose en plaques a pu être prouvé à la suite d'une importante étude de cohorte. Une nouvelle technique d'administration sous-cutanée de la lévodopa semble prometteuse. Enfin, de nombreuses études confirment l'efficacité et l'excellente tolérance des anticorps anti-CGRP (Calcitonine Gene Related Protein).

Benign EEG for prognostication of favorable outcome after cardiac arrest: A reappraisal.

AIM: The current EEG role for prognostication after cardiac arrest (CA) essentially aims at reliably identifying patients with poor prognosis ("highly malignant" patterns, defined by Westhall et al. in 2014). Conversely, "benign EEGs", defined by the absence of elements of "highly malignant" and "malignant" categories, has limited sensitivity in detecting good prognosis. We postulate that a less stringent "benign EEG" definition would improve sensitivity to detect patients with favorable outcomes. METHODS: Retrospectively assessing our registry of unconscious adults after CA (1.2018-8.2021), we scored EEGs within 72 h after CA using a modified "benign EEG" classification (allowing discontinuity, low-voltage, or reversed anterio-posterior amplitude development), versus Westhall's "benign EEG" classification (not allowing the former items). We compared predictive performances towards good outcome (Cerebral Performance Category 1-2 at 3 months), using 2x2 tables (and binomial 95% confidence intervals) and proportions comparisons. RESULTS: Among 381 patients (mean age 61.9 ± 15.4 years, 104 (27.2%) females, 240 (62.9%) having cardiac origin), the modified "benign EEG" definition identified a higher number of patients with potential good outcome (252, 66%, vs 163, 43%). Sensitivity of the modified EEG definition was 0.97 (95% CI: 0.92-0.97) vs 0.71 (95% CI: 0.62-0.78) (p < 0.001). Positive predictive values (PPV) were 0.53 (95% CI: 0.46-0.59) versus 0.59 (95% CI: 0.51-0.67; p = 0.17). Similar statistics were observed at definite recording times, and for survivors. DISCUSSION: The modified "benign EEG" classification demonstrated a markedly higher sensitivity towards favorable outcome, with minor impact on PPV. Adaptation of "benign EEG" criteria may improve efficient identification of patients who may reach a good outcome.

[Neurology : what's new in 2021]. / Neurologie.

In 2021, we assisted to the publication of new diagnostic criteria, classifications, and guidelines (CIDP, brain tumors, auto-immune encephalitis). Several studies helped to define the pharmacological management of focal and generalized epileptic seizures and epilepsy in pregnant women. The availability of biomarkers and the approval of immunotherapies are modifying the landscape of dementia management. Endovascular interventions without previous thrombolysis seems to be effective in anterior circulation acute ischemic stroke (AIS) and severe posterior circulation AIS. Neurologic complications of Sars-CoV-2 infection were further studied, as well as the efficacy of vaccines in immunosuppressed patients. New molecules and techniques show promising results for the treatment of migraine and cluster headache.

L'année 2021 a été marquée par la publication des nouveaux critères diagnostiques, classifications et guidelines (polyradiculonévrite inflammatoire démyélinisante chronique, tumeurs cérébrales, encéphalites autoimmunes). L'attitude thérapeutique dans les épilepsies focales ou généralisées et l'épilepsie chez la femme enceinte a été mieux définie. Les marqueurs biologiques et les immunothérapies modifient le paysage de la prise en charge des démences. Le traitement endovasculaire des AVC de la circulation antérieure semble efficace indépendamment d'une thrombolyse préalable, ainsi qu'en cas d'AVC sévère de la circulation postérieure. Les complications neurologiques du SARS-CoV-2 ont été éclaircies et l'efficacité des vaccins étudiée chez les patients immunosupprimés. Plusieurs nouvelles molécules et techniques montrent des résultats prometteurs pour les migraines et céphalées en grappe.

Clinical phenotype modulates brain's myelin and iron content in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is associated with brain pathology extending beyond temporal lobe structures. We sought to look for informative patterns of brain tissue properties in TLE that go beyond the established morphometry differences. We hypothesised that volume differences, particularly in hippocampus, will be paralleled by changes in brain microstructure. The cross-sectional study included TLE patients (n = 25) from a primary care center and sex-/age-matched healthy controls (n = 55). We acquired quantitative relaxometry-based magnetic resonance imaging (MRI) data yielding whole-brain maps of grey matter volume, magnetization transfer (MT) saturation, and effective transverse relaxation rate R2* indicative for brain tissue myelin and iron content. For statistical analysis, we used the computational anatomy framework of voxel-based morphometry and voxel-based quantification. There was a positive correlation between seizure activity and MT saturation measures in the ipsilateral hippocampus, paralleled by volume differences bilaterally. Disease duration correlated positively with iron content in the mesial temporal lobe, while seizure freedom was associated with a decrease of iron in the very same region. Our findings demonstrate the link between TLE clinical phenotype and brain anatomy beyond morphometry differences to show the impact of disease burden on specific tissue properties. We provide direct evidence for the differential effect of clinical phenotype characteristics on processes involving tissue myelin and iron in mesial temporal lobe structures. This study offers a proof-of-concept for the investigation of novel imaging biomarkers in focal epilepsy.

Cardiac phenotype in ATP1A3-related syndromes: A multicenter cohort study.

OBJECTIVE: To define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes. METHODS: Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl+/-) to determine the sequence of events in seizure-related cardiac death. RESULTS: Ninety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities were found in 52 of 87 (60%) with AHC, 2 of 3 (67%) with CAPOS, and 6 of 9 (67%) with RDP. Serial ECGs showed dynamic changes in 10 of 18 patients with AHC. The first Holter ECG was abnormal in 24 of 65 (37%) cases with AHC and RDP with either repolarization or conduction abnormalities. Echocardiography was normal. Cardiac intervention was required in 3 of 98 (≈3%) patients with AHC. In the mouse model, resting ECGs showed intracardiac conduction delay; during induced seizures, heart block or complete sinus arrest led to death. CONCLUSIONS: We found increased prevalence of ECG dynamic abnormalities in all ATP1A3-related syndromes, with a risk of life-threatening cardiac rhythm abnormalities equivalent to that in established cardiac channelopathies (≈3%). Sudden cardiac death due to conduction abnormality emerged as a seizure-related outcome in murine Atp1a3-related disease. ATP1A3-related syndromes are cardiac diseases and neurologic diseases. We provide guidance to identify patients potentially at higher risk of sudden cardiac death who may benefit from insertion of a pacemaker or implantable cardioverter-defibrillator.

EEG patterns associated with present cortical SSEP after cardiac arrest.

BACKGROUND: After cardiac arrest (CA), present cortical somatosensory evoked potentials (N20 response of SSEPs) have low predictive value for good outcome and might be redundant with EEG. AIMS: To determine whether specific features, or rather global, standardized EEG assessments, are reliably associated with cortical SSEP occurrence after cardiac arrest (CA). METHODS: In a prospective CA registry, EEGs recorded within 72 hours were scored according to the ACNS nomenclature, and also categorized into "benign," "malignant," and "highly malignant." Correlations between EEGs and SSEPs (bilaterally absent vs present), and between EEGs/SSEPs and outcome (good: CPC 1-2) were assessed. RESULTS: Among 709 CA episodes, 532 had present N20 and 366 "benign EEGs." While EEG categories as well as background, epileptiform features, and reactivity differed significantly between patients with and without N20 (each P < .001), only "benign EEG" was almost universally associated with present N20: 99.5% (95%CI: 97.9%-99.9%) PPV. The combination of "benign EEG" and present N20 showed similar PPV for good outcome as "benign" EEG alone: 69.0% (95% CI: 65.2-72.4) vs 68.6% (95% CI: 64.9-72.0). CONCLUSION: Global EEG ("benign") assessment, rather than single EEG features, can reliably predict cortical SSEP occurrence. SSEP adjunction does not increase EEG prognostic performance toward good outcome. SSEP could therefore be omitted in patients with "benign EEG."

Standardized EEG interpretation in patients after cardiac arrest: Correlation with other prognostic predictors.

INTRODUCTION: Standardized EEG patterns according to the American Clinical Neurophysiology Society (ACNS) ("highly malignant", "malignant" and "benign") demonstrated good correlation with outcome after cardiac arrest (CA). However, this approach relates to EEGs after target temperature management (TTM), and correlation to other recognized outcome predictors remains unknown. OBJECTIVES: To investigate the relationship between categorized EEG and other outcome predictors, during and after TTM, at different temperatures. METHODS: In a prospective adult CA registry between 01.2014 and 06.2017, EEG at day one and two after CA were reclassified into pre-defined categories. Correlations between EEG and clinical, biochemical, neurophysiological outcome predictors, and prognosis (CPC at three months; good: 1-2), were assessed. RESULTS: Of 203 CA episodes, 31.5% were managed targeting 33 °C, 60.6% targeting 36 °C, and 7.9% with spontaneous temperature. "Highly malignant" EEG was found in 36.7% of patients at day one (predicting poor prognosis with 91% specificity -95%CI: 83%-97%-, and 63% sensitivity -95% CI: 53%-72%), and 27.1% at day two. "Benign" EEG occurred in 19.2% at day one (sensitivity to good prognosis: 35% -95%CI: 26%-46%-, positive predictive value: 89% -95% CI: 75%-97%), and in 33.2% at day two. Categorized EEG showed robust correlations with all prognostic predictors. Results were similar between EEGs recorded at day one or two, and, especially for poor prognosis, across TTM targets. DISCUSSION: Standardized EEG categorization after CA shows strong correlation with other outcome predictors, without marked variation across EEG recording time or TTM targets, underscoring its prognostic role in a multimodal approach.

[Neurology]. / Neurologie.

Ocrelizumab (Ocrevus), an anti-CD20 monoclonal antibody, has been approved for the treatment of multiple sclerosis. Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis. A form of gene therapy, patisiran, has shown positive results in transthyretin familial amyloidosis. In the treatment of headaches, particularly migraines, non-pharmacological approaches have shown some interesting results. The criteria for Lewy body dementia have been revised. Generic use of lamotrigine does not result in recrudescence of epileptic seizures or adverse effects.

L'ocrélizumab (Ocrevus), un anticorps monoclonal anti-CD20, a été homologué dans le traitement de la sclérose en plaques. L'éculizumab (Soliris) a été approuvé dans plusieurs pays pour les formes réfractaires de myasthénie grave généralisée séropositive. Une forme de thérapie génique, le patisiran a montré des résultats positifs dans l'amyloïdose à transthyrétine. Dans le traitement des céphalées, en particulier des migraines, les approches non pharmacologiques ont montré quelques avancées. Les critères de la démence à corps de Lewy ont été révisés. L'utilisation de génériques de la lamotrigine n'engendre pas de recrudescence de crises épileptiques ni d'effets indésirables.

Characterising subtypes of hippocampal sclerosis and reorganization: correlation with pre and postoperative memory deficit.

Neuropathological subtypes of hippocampal sclerosis (HS) in temporal lobe epilepsy (The 2013 International League Against Epilepsy classification) are based on the qualitative assessment of patterns of neuronal loss with NeuN. In practice, some cases appear indeterminate between type 1 (CA1 and CA4 loss) and type 2 HS (CA1 loss) and we predicted that MAP2 would enable a more stringent classification. HS subtypes, as well as the accompanying alteration of axonal networks, regenerative capacity and neurodegeneration have been previously correlated with outcome and memory deficits and may provide prognostic clinical information. We selected 92 cases: 52 type 1 HS, 15 type 2 HS, 18 indeterminate-HS and 7 no-HS. Quantitative analysis was carried out on NeuN and MAP2 stained sections and a labeling index (LI) calculated for six hippocampal subfields. We also evaluated hippocampal regenerative activity (MCM2, nestin, olig2, calbindin), degeneration (AT8/phosphorylated tau) and mossy-fiber pathway re-organization (ZnT3). Pathology measures were correlated with clinical epilepsy history, memory and naming test scores and postoperative outcomes, at 1 year following surgery. MAP2 LI in indeterminate-HS was statistically similar to type 2 HS but this clustering was not shown with NeuN. Moderate verbal and visual memory deficits were noted in all HS types, including 54% and 69% of type 2 HS. Memory deficits correlated with several pathology factors including lower NeuN or MAP2 LI in CA4, CA1, dentate gyrus (DG) and subiculum and poor preservation of the mossy fiber pathway. Decline in memory at 1 year associated with AT8 labeling in the subiculum and DG but not HS type. We conclude that MAP2 is a helpful addition in the classification of HS in some cases. Classification of HS subtype, however, did not significantly correlate with outcome or pre- or postoperative memory dysfunction, which was associated with multiple pathology factors including hippocampal axonal pathways, regenerative capacity and degenerative changes.

Novel Treatment and New Drugs in Epilepsy Treatment.

We now get benefit from more than 20 antiepileptic drugs (AEDs) in the care of people with epilepsy. Newer generation of AED is associated with a more favourable tolerability profile than older generation AEDs which makes them easier to use, despite similar efficacy. In order to define the place of newer generation AEDs in the therapy, we review here the main current guidelines about their use for a special issue concerning antiepileptic drugs in neurosurgical practice. We also discuss how to tailor the treatment with newer generation AEDs according to the patient's needs and comorbid conditions. We review different common setting that may require specific therapeutic considerations, i.e. elderly, pregnancy, HIV infection, tumours and hospital/critical care use. We also discuss the current evidence regarding the use of newer generation AEDs in the neurosurgical practice. We present the most recent commercially available newer AEDs (ezogabine, perampanel, brivacetam, everolimus), describing their mechanism of action, adverse effects and indication according to the type of seizure. We finally describe the promising AEDs that are currently under development or testing. This article is a special issue concerning antiepileptic drugs in neurosurgical practice.

[Neurology]. / Neurologie.

Aducanumab reduces the burden of amyloid plaques in Alzheimer's disease, with significant improvement of clinical scores. Endovascular thrombectomy is recommended in patients with acute stroke with proximal occlusion of the anterior circulation. CGRP antagonists and botulinum toxin are effective in migraine. ZIKA virus infection has been linked to the Guillain-Barré syndrome. Edaravone has been approved for amyotrophic lateral sclerosis. Two monoclonal antibodies (ocrelizumab and daclizumab) and siponimod show positive results in multiple sclerosis. Thalamotomy of ventral intermediate nucleus (by gamma-knife or by magnetic resonance-guided focused ultrasound) is effective in drug-resistant essential tremor. The dose-dependent risk of foetal malformations associated with valproate and topiramate is confirmed.

L'aducanumab réduit la présence de plaques amyloïdes dans la maladie d'Alzheimer, avec amélioration significative des scores cliniques. Dans l'AVC aigu, la thrombectomie endovasculaire est recommandée en présence d'une occlusion proximale de la circulation antérieure. La toxine botulinique est efficace dans la migraine chronique. L'infection à virus Zika est associée au syndrome de Guillain-Barré. L'édaravone a été approuvé pour la sclérose latérale amyotrophique. Deux anticorps monoclonaux (ocrélizumab et daclizumab) et le siponimod montrent des résultats positifs dans la sclérose en plaques. La thalamotomie du noyau ventral intermédiaire par gamma-knife et par ultrasons focalisés guidés par résonance magnétique est efficace dans le tremblement pharmaco-résistant. Le risque dose-dépendant de malformations fœtales liées au valproate et au topiramate est confirmé.

Electroencephalography Predicts Poor and Good Outcomes After Cardiac Arrest: A Two-Center Study.

OBJECTIVE: The prognostic role of electroencephalography during and after targeted temperature management in postcardiac arrest patients, relatively to other predictors, is incompletely known. We assessed performances of electroencephalography during and after targeted temperature management toward good and poor outcomes, along with other recognized predictors. DESIGN: Cohort study (April 2009 to March 2016). SETTING: Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Mayo Clinic, Rochester, MN). PATIENTS: Consecutive comatose adults admitted after cardiac arrest, identified through prospective registries. INTERVENTIONS: All patients were managed with targeted temperature management, receiving prespecified standardized clinical, neurophysiologic (particularly, electroencephalography during and after targeted temperature management), and biochemical evaluations. MEASUREMENTS AND MAIN RESULTS: We assessed electroencephalography variables (reactivity, continuity, epileptiform features, and prespecified "benign" or "highly malignant" patterns based on the American Clinical Neurophysiology Society nomenclature) and other clinical, neurophysiologic (somatosensory-evoked potential), and biochemical prognosticators. Good outcome (Cerebral Performance Categories 1 and 2) and mortality predictions at 3 months were calculated. Among 357 patients, early electroencephalography reactivity and continuity and flexor or better motor reaction had greater than 70% positive predictive value for good outcome; reactivity (80.4%; 95% CI, 75.9-84.4%) and motor response (80.1%; 95% CI, 75.6-84.1%) had highest accuracy. Early benign electroencephalography heralded good outcome in 86.2% (95% CI, 79.8-91.1%). False positive rates for mortality were less than 5% for epileptiform or nonreactive early electroencephalography, nonreactive late electroencephalography, absent somatosensory-evoked potential, absent pupillary or corneal reflexes, presence of myoclonus, and neuron-specific enolase greater than 75 µg/L; accuracy was highest for early electroencephalography reactivity (86.6%; 95% CI, 82.6-90.0). Early highly malignant electroencephalography had an false positive rate of 1.5% with accuracy of 85.7% (95% CI, 81.7-89.2%). CONCLUSIONS: This study provides class III evidence that electroencephalography reactivity predicts both poor and good outcomes, and motor reaction good outcome after cardiac arrest. Electroencephalography reactivity seems to be the best discriminator between good and poor outcomes. Standardized electroencephalography interpretation seems to predict both conditions during and after targeted temperature management.

FDG-PET hyperactivity pattern in anti-NMDAr encephalitis.

FDG-PET can show anteroposterior glucose metabolism gradient in anti-NMDAr encephalitis, but there are also suggestions that basal ganglia are involved. We examined FDG-PET scans in 5 consecutive episodes of serologically proven anti-NMDAr encephalitis, compared with healthy controls. We confirmed the anteroposterior metabolic gradient and found a significant FDG uptake increase in the caudate nuclei in episodes of varying intensity and delay from the onset of the symptoms. FDG-PET can be useful in the work-up of suspected anti-NMDAr encephalitis disclosing a characteristic cortical and sub-cortical metabolism pattern.

Cause of death and predictors of mortality in a community-based cohort of people with epilepsy.

OBJECTIVE: The risk of premature mortality is increased in people with epilepsy. The reasons for this and how it may relate to epilepsy etiology remain unclear. METHODS: The National General Practice Study of Epilepsy is a prospective, community-based cohort that includes 558 people with recurrent unprovoked seizures of whom 34% died during almost 25 years of follow-up. We assessed the underlying and immediate causes of death and their relationship to epilepsy etiology. Psychiatric and somatic comorbidities of epilepsy as predictors of mortality were scrutinized using adjusted Cox proportional hazards models. RESULTS: The 3 most common underlying causes of death were noncerebral neoplasm, cardiovascular, and cerebrovascular disease, accounting for 59% (111/189) of deaths, while epilepsy-related causes (e.g., sudden unexplained death in epilepsy) accounted for 3% (6/189) of deaths. In 23% (43/189) of individuals, the underlying cause of death was directly related to the epilepsy etiology; this was significantly more likely if death occurred within 2 years of the index seizure (percent ratio 4.28 [95% confidence interval 2.63-6.97]). Specific comorbidities independently associated with increased risk of mortality were neoplasms (primary cerebral and noncerebral neoplasm), certain neurologic diseases, and substance abuse. CONCLUSIONS: Comorbid diseases are important causes of death, as well as predictors of premature mortality in epilepsy. There is an especially strong relationship between cause of death and epilepsy etiology in the first 2 years after the index seizure. Addressing these issues may help stem the tide of premature mortality in epilepsy.

Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype.

Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur. Dysautonomia may occur during hemiplegia or in isolation. Premature mortality can occur in this patient group and is not fully explained. Preventable cardiorespiratory arrest from underlying cardiac dysrhythmia may be a cause. We analysed ECG recordings of 52 patients with alternating hemiplegia from nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of ATP1A3. Data on autonomic dysfunction, cardiac symptoms, medication, and family history of cardiac disease or sudden death were collected. All had 12-lead electrocardiogram recordings available for cardiac axis, cardiac interval, repolarization pattern, and J-point analysis. Where available, historical and prolonged single-lead electrocardiogram recordings during electrocardiogram-videotelemetry were analysed. Half the cohort (26/52) had resting 12-lead electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities. These abnormalities were significantly more common in people with alternating hemiplegia than in an age-matched disease control group of 52 people with epilepsy. The average corrected QT interval was significantly shorter in people with alternating hemiplegia than in the disease control group. J wave or J-point changes were seen in six people with alternating hemiplegia. Over half the affected cohort (28/52) had intraventricular conduction delay, or incomplete right bundle branch block, a much higher proportion than in the normal population or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia were more common in those ≥16 years old, compared with those <16 (P = 0.0095), even with a specific mutation (p.D801N; P = 0.045). Dynamic, beat-to-beat or electrocardiogram-to-electrocardiogram, changes were noted, suggesting the prevalence of abnormalities was underestimated. Electrocardiogram changes occurred independently of seizures or plegic episodes. Electrocardiogram abnormalities are common in alternating hemiplegia, have characteristics reflecting those of inherited cardiac channelopathies and most likely amount to impaired repolarization reserve. The dynamic electrocardiogram and neurological features point to periodic systemic decompensation in ATP1A3-expressing organs. Cardiac dysfunction may account for some of the unexplained premature mortality of alternating hemiplegia. Systematic cardiac investigation is warranted in alternating hemiplegia of childhood, as cardiac arrhythmic morbidity and mortality are potentially preventable.

Sporadic late-onset nemaline myopathy with MGUS: long-term follow-up after melphalan and SCT.

OBJECTIVE: Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure. This study aims to qualitatively assess the long-term treatment effect of high-dose melphalan (HDM) followed by autologous stem cell transplantation (SCT) in a series of 8 patients with SLONM-MGUS. METHODS: We performed a retrospective case series study (n = 8) on the long-term (1-8 years) treatment effect of HDM followed by autologous SCT (HDM-SCT) on survival, muscle strength, and functional capacities. RESULTS: Seven patients showed a lasting moderate-good clinical response, 2 of them after the second HDM-SCT. All of them had a complete, a very good partial, or a partial hematologic response. One patient showed no clinical or hematologic response and died. CONCLUSIONS: This case series shows the positive effect of HDM-SCT in this rare disorder. Factors that may portend an unfavorable outcome are a long disease course before the hematologic treatment and a poor hematologic response. Age at onset, level and type of M protein (κ vs λ), and severity of muscle weakness were not associated with a specific outcome. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with SLONM-MGUS, HDM-SCT increases the probability of survival and functional improvement.

Asystole in alternating hemiplegia with de novo ATP1A3 mutation.

Alternating hemiplegia is a rare condition presenting with episodes of hemiplegia, epileptic seizures and, at times, dysautonomic attacks. De novo ATP1A3 (Na(+)/K(+) ATPase subunit) mutations were recently found to be the most common cause. We report a patient with alternating hemiplegia with de novo ATP1A3 mutation who experienced new-onset episodes of collapse in early adulthood unrelated to seizures. An implantable cardiac loop recorder documented episodes of asystole up to 5 s long. Subsequently a permanent pacemaker was implanted. ATP1A3 heart expression may be the explanation for the association of alternating hemiplegia and asystole episodes. Alternating hemiplegia has been associated with an increased risk of sudden death and lethal cardiac arrhythmias may be causative. Patients may need referral for appropriate cardiac investigations, especially if there is a change in symptoms. This case highlights the importance of clinical vigilance in patients with alternating hemiplegia.