Seizure burden and neuropsychological outcomes of new-onset refractory status epilepticus: Systematic review.

Background: Long-term sequelae of the new onset refractory status epilepticus (NORSE) include the development of epilepsy, cognitive deficits, and behavioral disturbances. The prevalence of these complications has been previously highlighted in case reports and case series: however, their full scope has not been comprehensively assessed. Methods: We conducted a systematic review of the literature (PROSPERO ID CRD42022361142) regarding neurological and functional outcomes of NORSE at 30 days or longer following discharge from the hospital. A systematic review protocol was developed using guidance from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Of the 1,602 records for unique publications, 33 reports on adults and 52 reports on children met our inclusion criteria. They contained the description of 280 adults and 587 children of whom only 75.7 and 85% of patients, respectively had data on long-term follow-up. The mean age of adult and pediatric patients was 34.3 and 7.9 years, respectively; and the longest duration of follow up were 11 and 20 years, respectively. Seizure outcomes received major attention and were highlighted for 93.4 and 96.6% of the adult and pediatric NORSE patients, respectively. Seizures remained medically refractory in 41.1% of adults and 57.7% of children, while seizure freedom was achieved in only 26 and 23.3% of these patients, respectively. The long-term cognitive outcome data was provided for just 10.4% of the adult patients. In contrast, cognitive health data were supplied for 68.9% of the described children of whom 31.9% were moderately or severely disabled. Long-term functional outcomes assessed with various standardized scales were reported in 62.2 and 25.5% of the adults and children, respectively with majority of patients not being able to return to a pre-morbid level of functioning. New onset psychiatric disorders were reported in 3.3% of adults and 11.2% of children recovering from NORSE. Conclusion: These findings concur with previous observations that the majority of adult and pediatric patients continue to experience recurrent seizures and suffer from refractory epilepsy. Moderate to severe cognitive disability, loss of functional independence, and psychiatric disorders represent a hallmark of chronic NORSE signifying the major public health importance of this disorder.

Reducing seizure to needle times in nonconvulsive status epilepticus with multifaceted quality improvement initiatives.

OBJECTIVES: Delayed management of nonconvulsive status epilepticus (NCSE) can lead to an increased morbidity and mortality. We previously established that inefficient treatment of NCSE at our institution stemmed from delayed initiation of emergent anti-seizure medications (ASM). In the present study, we assessed the trajectories of these time parameters and determined patient outcomes following the specific quality improvement (QI) interventions. METHODS: The QI interventions, including the revision of the educational content for trainees and pharmacy workflow optimization were implemented between January 2019 and September 2021 by a dedicated multidisciplinary task force. The times needed to initiate and administer the ASMs for patients with NCSE as well as patient mortality were assessed in comatose and noncomatose patients and compared with the corresponding values prior to the interventions. RESULTS: There were 79 occurrences of NCSE in 74 patients. The median time from seizure detection on EEG to the order of the first and second ASM for NCSE was reduced by 4 (p = 0.83) and 8 min (p = 0.52), respectively compared to the times prior to the initiation of interventions. The median times from the order to administration of the first and third ASM for all NCSE occurrences were reduced by 8 and 10 min, respectively (p = 0.28 and p = 0.10). In the present cohort of comatose patients, the median time spent to order the first ASM was reduced by 16.5 min and the time to administer it reduced by 35 min compared to that in our previous study. The overall patient mortality was decreased by 11.1%. SIGNIFICANCE: More efficient delivery of rescue ASMs in patients with NCSE and improvement in their mortality can be achieved with multidisciplinary team efforts aimed at streamlining the functioning of pharmacy and strengthening the education of trainees and nurses.

Biopsy-Proven Amyloid-Beta Related Angiitis with Unusual Presentation and Long-Term Follow-Up.

Amyloid-beta related angiitis (ABRA) is a rare central nervous system inflammatory and vasculitic process. It is seen in patients with cerebral amyloid angiopathy (CAA) and thought to be mediated by an autoimmune reaction against cerebrovascular ß-amyloid. We describe the case of a patient with ABRA with clinical information and brain imaging over a 10-year period. The patient was hospitalized in 2018 for altered mental status, paranoia and hallucinations. Her symptoms started in 2009 with an episode of vertigo and loss of consciousness. From 2011-2019, she had multiple episodes of transient focal neurological deficits with overall cumulative progressive decline in cognition and functional status. Retrospective and comparative reviews of brain magnetic resonance imaging (MRI) from 2009-2019 showed waxing and waning vasogenic cerebral edema with overall progression of white matter hyperintensities and peripheral micro-hemorrhages consistent with inflammatory CAA. Re-examination of a brain biopsy from 2009 showed ABRA, and immunostaining was positive for ß-amyloid. She was treated with intravenous steroids with minimal symptomatic improvement. She was lost to our follow-up after hospital discharge. We describe the temporal progression of ABRA through serial brain imaging over a 10-year period. To our knowledge, this is the longest published follow-up duration of ABRA. The patient in our case had severe cognitive impairment and disability despite treatment with steroids.

Anti-Neurofascin Antibodies Associated with White Matter Diseases of the Central Nervous System: A Red Flag or a Red Herring?

Autoantibodies against nodal and paranodal proteins, specifically anti-neurofascin antibodies (ANFAs), have been recently described in central and peripheral nervous system demyelinating disorders. We retrospectively reviewed the charts of six individuals evaluated at our Multiple Sclerosis Program who tested positive for serum ANFAs on Western blot. We describe these patients' clinical and diagnostic findings and attempt to identify features that might guide clinicians in checking for ANFAs. In our series, the women-to-men ratio was 2:1. At presentation, the median age was 60 years (range 30-70). The clinical presentation was pleiotropic and included incomplete transverse myelitis (n = 3), progressive myelopathy (n = 1), recurrent symmetric polyneuropathy (n = 1), and nonspecific neurological symptoms (n = 1). Atypical features prompting further workup included coexisting upper and lower motor neuron features, older age at presentation with active disease, atypical spinal cord MRI features, and unusual cerebrospinal fluid findings. The serum ANFAs panel was positive for the NF-155 isoform in five patients (IgM n = 2; IgG n = 2; both n = 1) and the NF-140 isoform in two (IgG n = 2). Larger studies are needed to assess the relevance of ANFAs in demyelinating nervous system diseases, their impact on long-term clinical outcomes, and associated therapeutic implications.

Risk of seizure clusters and status epilepticus following rapid and ultra-rapid medication discontinuation during intracranial EEG monitoring.

OBJECTIVE: Anti-seizure medications (ASMs) are discontinued in the course of intracranial EEG (iEEG) monitoring for presurgical evaluation. The ASM withdrawal facilitates an emergence of seizures but may also precipitate seizure clusters (SC) and status epilepticus (SE). The aim of this study was to compare the rates of SC and SE during the ultra-rapid withdrawal (URW) and rapid withdrawal (RW) of ASMs during iEEG. METHODS: We performed a retrospective observational study of all consecutive patients with drug resistant epilepsy who completed iEEG at our comprehensive epilepsy center from 2012-2018. SC was defined as three or more seizures in 24 h with a return to baseline between the events. SE was defined as ≥ 5 min of clinical seizure or ≥ 10 min of ictal electrographic activity or series of seizures with no return to the neurological baseline between the events. RESULTS: Of 107 patients who completed iEEG with intracranial grid or strip electrodes, 46 (43%) were male. Median age at the time of iEEG was 35.4 years (interquartile range [IQR], 26.4 - 44.9). Ninety patients (84.1%) had all AEDs held on admission, while 16 patients (15%) underwent a rapid taper. The median time to first seizure was 15.1 (8.2 - 22.6) h. Sixty-two patients (57.9%) developed SC, while 10 (9.4%) developed SE. Twenty-six patients (36.1%) with these complications required intravenous lorazepam or other rescue ASMs, while the remaining patients had spontaneous resolution of seizures; intubations were not required. While there were differences in the proportions in patients who experienced SC, SE, or neither in the URW and RW groups, these differences were not significant at the 0.05 alpha level. SIGNIFICANCE: Ultra-rapid and rapid ASM withdrawal are accompanied by SC and SE the majority of which terminate spontaneously. These data support the use of either approach of the medication taper for seizure provocation in iEEG.

Treatment of focal hand dystonia: current status.

BACKGROUND: Focal hand dystonia (FHD) is usually adult-onset focal dystonia that can be associated with marked occupational and functional disability leading to reduced quality of life. METHODS: Relevant studies on treatment options for FHD, their limitations, and current recommendations were reviewed using the PubMed search until March 31, 2021. Besides, the reference lists of the retrieved publications were manually searched to explore other relevant studies. RESULTS: and conclusion Currently, botulinum toxin has the best evidence for treatment of FHD, and 20-90% of patients experience symptomatic improvement. However, its benefit is often limited by the reduction of muscle tonus acting on the muscle spindle. Different surgical modalities that have been used to treat focal hand dystonia include lesional surgery, deep brain stimulation, and magnetic resonance-guided focused ultrasound thalamotomy. Recent studies exploring the role of behavioral techniques, sensorimotor training, and neuromodulation for the treatment of focal hand dystonia have reported good outcomes, but larger studies are required before implementing these interventions in practice.

Rest tremor in dystonia: epidemiology, differential diagnosis, and pathophysiology.

BACKGROUND: The most common type of tremor reported in dystonia patients is postural and kinetic. There is uncertainty regarding the prevalence of rest tremor in dystonia. OBJECTIVE: This review focuses on the clinical and neurophysiological features of rest tremor in dystonia, its differential diagnosis, and methods to distinguish it from other rest tremor syndromes. METHODS: A PubMed search was done, and the available literature identified. Bibliography of the available literature was reviewed for relevant references. RESULTS: Rest tremor in dystonia has been reported with a variable frequency of 1.81-12.05%. The most common body distribution is arm, and it tends to be asymmetric. Most of the affected patients have multifocal and segmental dystonia. Rest tremor is a late-onset phenomenon associated with severe and spreading dystonia. Clinically, it is difficult to distinguish rest tremor in dystonia from other rest tremor syndromes based on tremor characteristics; however, other neurological signs can provide clues to differentiate these syndromes. Surface electromyography and other neurophysiological tests can help differentiate the various rest tremor syndromes. CONCLUSION: Rest tremor in dystonia can be differentiated from other rest tremor syndromes based on neurophysiological techniques. There is some evidence to suggest that SWEDDs could be a form of dystonic tremor, but further studies are required to clarify this diagnostic dilemma. Data regarding the treatment of rest tremor in dystonia are virtually nonexistent, and there is an urgent need for prospective studies focusing its medical management and to know the surgical targets.

Post-Thalamic Stroke Movement Disorders: A Systematic Review.

BACKGROUND: After a stroke, movement disorders are rare manifestations mainly affecting the deep structures of the brain like the basal ganglia (44%) and thalamus (37%), although there have been case studies of movement disorders in strokes affecting the cerebral cortex also. SUMMARY: This review aims to delineate the various movement disorders seen in association with thalamic strokes and tries to identify the location of the nuclei affected in each of the described movement disorders. Cases were identified through a search of PubMed database using different search terms related to post-thalamic stroke movement disorders and a secondary search of references of identified articles. We reviewed 2,520 research articles and only 86 papers met the inclusion criteria. Cases were included if they met criteria for post-thalamic stroke movement disorders. Case-cohort studies were also reviewed and will be discussed further. Key Messages: The most common post-stroke abnormal movement disorder reported in our review was dystonia followed by hemiataxia. There was a higher association between ischaemic stroke and movement disorder. Acute onset movement disorders were more common than delayed. The posterolateral thalamus was most commonly involved in post-thalamic stroke movement disorders.