Case report: Off-label use of low-dose perampanel in a 25-month-old girl with a pathogenic SYNGAP1 variant.

Introduction: Preclinical studies in a mouse model have shown that SYNGAP1 haploinsufficiency results in an epilepsy phenotype with excessive GluA2-AMPA insertion specifically on the soma of fast-spiking parvalbumin-positive interneurons associated with significant dysfunction of cortical gamma homeostasis that was rescued by perampanel (PER), an AMPA receptor blocker. In this single case, we aimed to investigate the presence of dysregulated cortical gamma in a toddler with a pathogenic SYNGAP1 variant and report on the effect of low-dose PER on electroencephalogram (EEG) and clinical profile. Methods: Clinical data from physician's clinic notes; genetic testing reports; developmental scores from occupational therapy, physical therapy, speech and language therapy evaluations; and applied behavioral analysis reports were reviewed. Developmental assessments and EEG analysis were done pre- and post-PER. Results: Clinically, the patient showed improvements in the developmental profile and sleep quality post-PER. EEG spectral power analysis in our patient revealed a loss of gamma power modulation with behavioral-state transitions similar to what was observed in Syngap1+/- mice. Furthermore, the administration of low-dose PER rescued the dysfunctional cortical gamma homeostasis, similar to the preclinical study. However, as in the epileptic mice, PER did not curb epileptiform discharges or clinical seizures. Conclusion: Similar to the Syngap1+/- mice, cortical gamma homeostasis was dysregulated in the patient. This dysfunction was rescued by PER. These encouraging results necessitate further validation of gamma dysregulation as a potential translational EEG biomarker in SYNAP1-DEE. Low-dose PER can be explored as a therapeutic option through clinical trials.

Ambulatory Local Field Potential Recordings from the Thalamus in Epilepsy: A Feasibility Study.

INTRODUCTION: Stimulation of the thalamus is gaining favor in the treatment of medically refractory multifocal and generalized epilepsy. Implanted brain stimulators capable of recording ambulatory local field potentials (LFPs) have recently been introduced, but there is little information to guide their use in thalamic stimulation for epilepsy. This study sought to assess the feasibility of chronically recording ambulatory interictal LFP from the thalamus in patients with epilepsy. METHODS: In this pilot study, ambulatory LFP was recorded from patients who underwent sensing-enabled deep brain stimulation (DBS, 2 participants) or responsive neurostimulation (RNS, 3 participants) targeting the anterior nucleus of the thalamus (ANT, 2 electrodes), centromedian nucleus (CM, 7 electrodes), or medial pulvinar (PuM, 1 electrode) for multifocal or generalized epilepsy. Time-domain and frequency-domain LFP was investigated for epileptiform discharges, spectral peaks, circadian variation, and peri-ictal patterns. RESULTS: Thalamic interictal discharges were visible on ambulatory recordings from both DBS and RNS. At-home interictal frequency-domain data could be extracted from both devices. Spectral peaks were noted at 10-15 Hz in CM, 6-11 Hz in ANT, and 19-24 Hz in PuM but varied in prominence and were not visible in all electrodes. In CM, 10-15 Hz power exhibited circadian variation and was attenuated by eye opening. CONCLUSION: Chronic ambulatory recording of thalamic LFP is feasible. Common spectral peaks can be observed but vary between electrodes and across neural states. DBS and RNS devices provide a wealth of complementary data that have the potential to better inform thalamic stimulation for epilepsy.

Diagnosis of autism in a rare case of tyrosine hydroxylase deficiency: a case report.

BACKGROUND: Tyrosine hydroxylase deficiency (THD) is a rare movement disorder with broad phenotypic expression caused by bi-allelic mutations in the TH gene, which encode for tyrosine hydroxylase (TH) protein. Some patients with THD have improvement in dystonia with carbidopa-levodopa, a synthetic form of dopamine typically used in Parkinson's disease, and are considered to have dopa-responsive THD. THD has been found in 0.5-1 per million persons, although due to overlapping symptoms with other disorders and the need for genetic testing, prevalence is likely underestimated. Existing literature describes some patients with THD having intellectual disability, but comorbid autism spectrum disorder (ASD) has not been reported. CASE PRESENTATION: A nearly 3-year-old boy was referred to pediatric neurology due to hypotonia, delayed motor milestones, and expressive speech delay. Whole exome sequencing confirmed tyrosine hydroxylase deficiency, detecting a novel variant p.S307C first reported here. The child was treated with carbidopa-levodopa with an excellent response, resulting in improved balance, fewer falls, and improved ability to jump, run and climb stairs. He was determined to have dopa-responsive THD. Due to his delays in expressive speech, the boy also had an assessment with a developmental and behavioral pediatrician, who identified a pattern of social pragmatic speech delay, sensory sensitivities, and restricted interests, and determined that he met criteria for a diagnosis of ASD. CONCLUSIONS: While ASD can stand alone as a clinical diagnosis, it is also a cardinal feature of other genetically-based neurological disorders. To our knowledge, this is the first case that describes a patient with both disorders. Perhaps THD may be among the genetic disorders linked with ASD.

Tailored Hemispherotomy Using Tractography-Guided Laser Interstitial Thermal Therapy.

BACKGROUND: Medically refractory hemispheric epilepsy is a devastating disease with significant lifetime costs and social burden. Functional hemispherotomy is a highly effective treatment for hemispheric epilepsy but is associated with significant complication rates. Percutaneous hemispherotomy through laser interstitial thermal therapy (LITT) based on morphological MRI has been recently described in a single patient but not replicated in the literature. OBJECTIVE: To describe the first 2 cases of tractography-guided interstitial laser hemispherotomy and their short-term outcomes. METHODS: Two 11-year-old male patients with medically refractory epilepsy secondary to perinatal large vessel infarcts were referred for hemispherotomy. Both patients underwent multitrajectory LITT to disconnect the remaining pathological hemisphere, using tractography to define targets and assess structural outcomes. RESULTS: Both cases had minor complication of small intraventricular/subarachnoid hemorrhage not requiring additional intervention. Both patients remain seizure-free at all follow-up visits. CONCLUSION: LITT hemispherotomy can produce seizure freedom with short hospitalization and recovery. Tractography allows surgical planning to be tailored according to individual patient anatomy, which often is distorted in perinatal stroke. Minimally invasive procedures offer the greatest potential for seizure freedom without the risks of an open hemispherotomy.

Braquimetatarsia: propuesta de tratamiento en base a técnicas de alargamiento: a propósito de dos casos / Brachymetatarsia: treatment proposal based on lengthening techniques: about two cases / Braquimetatarsia: proposta de tratamento baseada em técnicas de alongamento: sobre dois casos

Braquimetatarsia es el acortamiento anormal de uno o más metatarsianos. Tiene una incidencia de 0.02%-0.05% predominando en mujeres de 25 a 1. En un 72% puede ser bilateral. La etiología no es clara pero se plantea el cierre prematuro de la fisis dando un retardo en el crecimiento. La mayoría de las veces presenta síntomas causados por alteración en la mecánica de la parábola metatarsal como dolor e hiperqueratosis. Puede existir metatarsalgia y agregar en la evolución desviaciones digitales adicionales. El principal motivo de consulta es estético. El objetivo del reporte es mostrar dos técnicas quirúrgicas y los resultados clínicos correspondientes usando el score AOFAS, además de los resultados imágenológicos con hasta 5 años de seguimiento. Se describen dos pacientes y se analizan dos técnicas quirúrgicas diferentes para alargar los metatarsianos. Se trata de alargamientos agudos con interposición de injerto intercalar, en un caso mediante el procedimiento de Sandro Gianini con injerto de cresta ilíaca y en el otro con injerto de metatarsiano adyacente con modificación de la longitud del segundo y tercer metatarsiano restituyendo en ambos casos la parábola metatarsal. Obtuvimos buenos resultados al igual que series numerosas pudiendo recomendarse en casos similares.

Brachymetarsal is the abnormal shortening of one or more metatarsals. It has an incidence of 0.02%-0.05%, predominantly in women from 25 to 1. In 72% it can be bilateral. The etiology is not clear, but premature closure of the physis is suggested, giving growth retardation. Most of the time it presents symptoms caused by an alteration in the mechanics of the metatarsal parabola, such as pain and hyperkeratosis. There may be metatarsalgia and add additional digital deviations in the evolution. The main reason for consultation is aesthetic. The objective of the work is to show the surgical technique and the clinical results using the AOFAS score, in addition to the imaging results with up to 5 years of follow-up. Two patients are described and two different surgical techniques to lengthen the metatarsals are analyzed. These are acute lengthenings with intercalary graft interposition, in one case using the S.Gianini procedure with an iliac crest graft and in the other with an adjacent metatarsal graft with modification of the length of the second and third metatarsals, restoring in both cases the metatarsal parabola. We obtained good results. results as well as numerous series and can be recommended in similar cases.

Braquimetatarsal é o encurtamento anormal de um ou mais metatarsos. Tem incidência de 0,02%-0,05%, predominantemente em mulheres de 25 a 1 ano. Em 72% pode ser bilateral. A etiologia não é clara, mas sugere-se o fechamento prematuro da fise, causando retardo de crescimento. Na maioria das vezes apresenta sintomas decorrentes de uma alteração na mecânica da parábola metatarsal, como dor e hiperqueratose. Pode haver metatarsalgia e adicionar desvios digitais adicionais na evolução. O principal motivo da consulta é a estética. O objetivo do trabalho é mostrar a técnica cirúrgica e os resultados clínicos utilizando o escore AOFAS, além dos resultados de imagem com até 5 anos de seguimento. Materiais e métodos: São incluídos dois pacientes e analisadas duas técnicas cirúrgicas diferentes para alongar os metatarsos. São alongamentos agudos com interposição de enxerto intercalar, em um caso utilizando a técnica de S. Gianini com enxerto de crista ilíaca e no outro com enxerto de metatarso adjacente com modificação do comprimento do segundo e terceiro metatarsos, restaurando em ambos os casos o metatarso parábola. Obtivemos bons resultados, bem como inúmeras séries, podendo ser recomendados em casos semelhantes.

Digital reconstruction of infraslow activity in human intracranial ictal recordings using a deconvolution-based inverse filter.

Infraslow activity (ISA) is a biomarker that has recently become of interest in the characterization of seizure recordings. Recent data from a small number of studies have suggested that the epileptogenic zone may be identified by the presence of ISA. Investigation of low frequency activity in clinical seizure recordings, however, has been hampered by technical limitations. EEG systems necessarily include a high-pass filter early in the measurement chain to remove large artifactual drifts that can saturate recording elements such as the amplifier. This filter, unfortunately, attenuates legitimately seizure-related low frequencies, making ISA difficult to study in clinical EEG recordings. In this study, we present a deconvolution-based digital inverse filter that allows recovery of attenuated low frequency activity in intracranial recordings of temporal lobe epilepsy patients. First, we show that the unit impulse response (UIR) of an EEG system can be characterized by differentiation of the system's step response. As proof of method, we present several examples that show that the low frequency component of a high-pass filtered signal can be restored by deconvolution with the UIR. We then demonstrate that this method can be applied to biologically relevant signals including clinical EEG recordings obtained from seizure patients. Finally, we discuss how this method can be applied to study ISA to identify and assess the seizure onset zone.

Stereotactic laser anterior corpus callosotomy for Lennox-Gastaut syndrome.

OBJECTIVE: Corpus callosotomy is an effective palliative treatment for drug-resistant Lennox-Gastaut syndrome (LGS). Laser interstitial thermal therapy has been increasingly used in the treatment of epilepsy. Here, we assess the safety and effectiveness of minimally invasive stereotactic laser anterior corpus callosotomy (SLACC) for drop attacks in LGS. METHODS: We reviewed sequential cases of patients with medically intractable LGS who underwent SLACC using a two-cannula technique between November 2014 and July 2019. Pre- and postoperative magnetic resonance imaging was used to measure the anteroposterior length of callosal ablation (contrast-enhancing lesion) and estimated disconnection (gap in tract projections on diffusion tensor imaging). Patients were followed longitudinally to assess clinical outcomes. RESULTS: Ten patients were included in this study. The median age was 33 (range = 11-52) years, median duration of epilepsy was 26 (range = 10-49) years, and median duration of postoperative follow-up was 19 (range = 6-40) months. In the anteroposterior direction, 53 ± 7% (mean ± SD) of the corpus callosum was ablated and 62 ± 19% of the corpus callosum was estimated to be disconnected. Six (60%) of 10 patients achieved >80% seizure reduction, two (20%) of whom became seizure-free. Eight (80%) patients had >80% reduction in drop attacks, five (50%) of whom became free of drop attacks. Three patients subsequently underwent laser posterior callosotomy with further improvement in drop attacks and/or overall seizure frequency. One patient had an asymptomatic intracerebral hemorrhage along the cannula tract. One patient developed significant aggression after becoming seizure-free. SIGNIFICANCE: Seizure outcomes following SLACC were comparable to previously reported outcomes of open callosotomy, with reasonable safety profile. SLACC appears to be an effective alternative to open anterior corpus callosotomy with minimal postoperative discomfort and a short recovery period.

Access to Health Care for Pregnant Arabic-Speaking Refugee Women and Mothers in Germany.

Refugee women often encounter multiple barriers when accessing ante-, peri-, and postnatal care. The aim of this study was to investigate how premigration experiences, conceptions about pregnancy and childbirth, health literacy, and language skills influence access to health care, experiences of health care, and childbirth. A total of 12 semi-structured interviews with refugee women from Iraq, Syria, and Palestine were conducted in the city of Dresden. Content analysis was applied using Levesque's access model as a framework. Results indicate that conceptions of pregnancy and childbirth and premigration experiences influence women's behaviors and experiences of pregnancy and childbirth. They contribute to barriers in accessing health care and lead to negative health outcomes. In view of limited health literacy, poor language skills, lack of information, and missing translators, female relatives in countries of origin remain an important source of information. Improved access to services for refugee women is needed.

Parkinsonism and neurological manifestations of influenza throughout the 20th and 21st centuries.

PURPOSE: Given the recent paper by Jang et al. on "A Highly Pathogenic H5N1 Influenza Virus" which reported a novel animal model of parkinsonism, we aimed to perform a complete historical review of the 20th and 21st century literature on parkinsonism and neurological manifestations of influenza. SCOPE: There were at least twelve major flu pandemics reported in the literature in the 20th and 21st century. Neurological manifestations most prevalent during the pandemics included delirium, encephalitis, ocular abnormalities, amyotrophy, myelopathy, radiculopathy, ataxia and seizures. Very little parkinsonism was reported with the exception of the 1917 cases originally described by von Economo. CONCLUSIONS: To date there have been surprisingly few cases of neurological issues inclusive of parkinsonism associated with influenza pandemics. Given the recent animal model of H5N1 influenza associated parkinsonism, the medical establishment should be prepared to evaluate for the re-emergence of parkinsonism during future outbreaks.