Focal cortical malformations in children with early infantile epilepsy and PCDH19 mutations: case report.

In this case report we assess the occurrence of cortical malformations in children with early infantile epilepsy associated with variants of the gene protocadherin 19 (PCDH19). We describe the clinical course, and electrographic, imaging, genetic, and neuropathological features in a cohort of female children with pharmacoresistant epilepsy. All five children (mean age 10y) had an early onset of epilepsy during infancy and a predominance of fever sensitive seizures occurring in clusters. Cognitive impairment was noted in four out of five patients. Radiological evidence of cortical malformations was present in all cases and, in two patients, validated by histology. Sanger sequencing and Multiplex Ligation-dependent Probe Amplification analysis of PCDH19 revealed pathogenic variants in four patients. In one patient, array comparative genomic hybridization showed a microdeletion encompassing PCDH19. We propose molecular testing and analysis of PCDH19 in patients with pharmacoresistant epilepsy, with onset in early infancy, seizures in clusters, and fever sensitivity. Structural lesions are to be searched in patients with PCDH19 pathogenic variants. Further, PCDH19 analysis should be considered in epilepsy surgery evaluation even in the presence of cerebral structural lesions. WHAT THIS PAPER ADDS: Focal cortical malformations and monogenic epilepsy syndromes may coexist. Structural lesions are to be searched for in patients with protocadherin 19 (PCDH19) pathogenic variants with refractory focal seizures.

SERPINI1 pathogenic variants: An emerging cause of childhood-onset progressive myoclonic epilepsy.

Progressive myoclonic epilepsies are rare neurodegenerative diseases with a wide spectrum of clinical presentations and genetic heterogeneity that render their diagnosis perplexing. Discovering new imputable genes has been an ongoing process in recent years. We present two pediatric cases of progressive myoclonic epilepsy with SERPINI1 pathogenic variants that lead to a severe presentation; we highlight the importance of including this gene, previously known as causing an adult-onset dementia-epilepsy syndrome, in the genetic work-up of childhood-onset progressive myoclonic epilepsies.

A child with ictal vocalizations and generalized epilepsy.

Ictal vocalizations in the form of both articulate speech and non-speech vocalizations have been described in focal epilepsies, with seizures originating mainly from the frontal and temporal lobe, however, this phenomenon has not been described in generalized epilepsies. We report the case of an adolescent boy with juvenile-onset generalized epilepsy who presented with ictal "ovine vocalizations" (resembling the bleating of sheep). The ictal EEG revealed a clear correlate of vocalizations with time-locked generalized spikes and polyspike discharges. The 3T cerebral MRI ruled out any focal lesion. The boy is currently seizure-free under valproic acid, after twelve months of follow-up. We conclude that ictal non-speech vocalizations may be observed not only in focal or structural epilepsies, but also in generalized epilepsies; the exact underlying mechanism of this phenomenon needs to be further delineated. [Published with video sequence].

Stroke-like Phenomena Revealing Multifocal Cerebral Vasculitis in Pediatric Lyme Neuroborreliosis.

Stroke-like presentation in Lyme neuroborreliosis is rare in the pediatric age group. We report a previously healthy 12-year-old boy who presented with acute left hemiparesis and meningeal signs. Neuroimaging failed to reveal any cerebral infarction but demonstrated a multifocal cerebral vasculitis involving small, medium and large-sized vessels affecting both the anterior and posterior circulation. Concentric contrast enhancement of the basilar artery was also observed. Further investigations and laboratory findings were consistent with Lyme neuroborreliosis. A rapidly favorable clinical outcome was obtained with appropriate antibiotic treatment along with antiaggregants and steroids. Lyme neuroborreliosis should be considered in the diagnostic differential, not only in adults but also among children, especially in the context of an unexplained cerebral vasculitis.

Multifocal motor neuropathy with high titers of anti-MAG antibodies.

Multifocal motor neuropathy (MMN) and anti-myelin-associated glycoprotein (anti-MAG)-associated neuropathy are clinically and electrophysiologically distinct entities. We describe a patient with characteristic features of both neuropathies, raising the possibility of an overlap syndrome. A 49-year-old patient reported a history of slowly progressive predominantly distal tetraparesis, with mild sensory deficits. Nerve conduction studies demonstrated persistent motor conduction blocks outside compression sites, typical of MMN. Laboratory findings revealed persistently high titers of anti-MAG immunoglobulin Mλ (IgMλ) paraprotein in the context of a monoclonal gammapathy of unknown significance. Skin biopsy of distal lower limb revealed IgM positive terminal nerve perineurium deposits. This case suggests that the distinction between subtypes of chronic inflammatory neuropathies may not be as clear as initially thought, and that the pattern of pathogenicity of anti-MAG antibodies may vary.

Auditory verbal hallucinations of epileptic origin.

Complex auditory hallucinations are often characterized by hearing voices and are then called auditory verbal hallucinations (AVHs). While AVHs have been extensively investigated in psychiatric patients suffering from schizophrenia, reports from neurological patients are rare and, in most cases, incomplete. Here, we characterize AVHs in 9 patients suffering from pharmacoresistant epilepsy by analyzing the phenomenology of AVHs and patients' neuropsychological and lesion profiles. From a cohort of 352 consecutively examined patients with epilepsy, 9 patients suffering AVHs were identified and studied by means of a semistructured interview, neuropsychological tests, and multimodal imaging, relying on a combination of functional and structural neuroimaging data and surface and intracranial EEG. We found that AVHs in patients with epilepsy were associated with prevalent language deficits and damage to posterior language areas and basal language areas in the left temporal cortex. Auditory verbal hallucinations, most of the times, consisted in hearing a single voice of the same gender and language as the patient and had specific spatial features, being, most of the times, perceived in the external space, contralateral to the lesion. We argue that the consistent location of AVHs in the contralesional external space, the prominence of associated language deficits, and the prevalence of lesions to the posterior temporal language areas characterize AVHs of neurological origin, distinguishing them from those of psychiatric origin.

Opsoclonus-myoclonus syndrome in anti-N-methyl-D-aspartate receptor encephalitis.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis has been recently reported as autoimmune/paraneoplastic encephalitis, affecting mostly young females. OBJECTIVE: To describe opsoclonus-myoclonus syndrome in association with anti-NMDAR antibodies. DESIGN: Case report. SETTING: Geneva University Hospital. Patient A 23-year-old woman with opsoclonus-myoclonus syndrome. RESULTS: Two weeks after an episode of gastroenteritis, the patient developed symptoms of depression associated with psychomotor slowing, progressive gait instability, and opsoclonus-myoclonus. Cerebrospinal fluid examination showed mild lymphocytic pleocytosis and intrathecal IgG synthesis with oligoclonal bands. The patient's condition worsened rapidly to an akinetic mutism, followed by a period of agitation, delirium, and hallucinations. These gradually subsided; however, a frontal behavior and executive dysfunction persisted 5 months after symptom presentation. No tumor was found. Anti-NMDAR antibodies were found in the cerebrospinal fluid. CONCLUSIONS: Opsoclonus-myoclonus may occur in patients with anti-NMDAR encephalitis. Prompt diagnosis of this disorder is important because after tumor removal and immunomodulatory therapies it has a relatively good prognosis.

EEG source imaging in pediatric epilepsy surgery: a new perspective in presurgical workup.

PURPOSE: Epilepsy is a relatively frequent disease in children, with considerable impact on cognitive and social life. Successful epilepsy surgery depends on unambiguous focus identification and requires a comprehensive presurgical workup, including several neuroimaging techniques [magnetic resonance imaging, positron emission tomography (PET), and single-photon emission computed tomography (SPECT)]. These may be difficult to apply in younger or developmentally delayed children or both, requiring sedation, and hence, a significant workforce. Modern electric source imaging (ESI) provides accurate epileptic source-localization information in most patients, with minimal patient discomfort or need for cooperation. The purpose of the present study was to determine the usefulness of ESI in pediatric EEG recordings performed with routine electrode arrays. METHODS: Preoperative EEGs recorded from 19 to 29 scalp electrodes were reviewed, and interictal epileptiform activity was analyzed by using a linear source-imaging procedure (depth-weighted minimum norm) in combination with statistical parametric mapping. RESULTS: In 27 (90%) of 30 patients, the ESI correctly localized the epileptogenic region. These numbers compare favorably with the results from other imaging techniques in the same patients (PET, 82%; ictal SPECT, 70%). In extratemporal epilepsy, ESI was correct in all cases, and in temporal lobe epilepsy, in 10 of 13 cases. In two temporal lobe patients showing less-accurate ESI results, 128-electrode data could be analyzed, and in both cases, the 128-electrode ESI was correct. CONCLUSIONS: ESI with standard clinical EEG recordings provides excellent localizing information in pediatric patients, in particular in extratemporal lobe epilepsy. The lower yield in temporal lobe epilepsy seems to be due to undersampling of basal temporal areas with routine scalp recordings.

The global burden of measles in the year 2000--a model that uses country-specific indicators.

The estimation of the global burden of measles is challenging in the absence of reliable and comparable surveillance systems worldwide. A static model is described that enables estimation of measles morbidity, mortality, and disability for the year 2000 on the basis of country-specific information (i.e., demographic profile, vaccine coverage, and estimates of case-fatality ratios). This approach estimated a global incidence of 39.9 million measles cases, 777,000 deaths, and 28 million disability-adjusted life years. The World Health Organization regions of Africa and Southeast Asia had 70% of incident cases and 84% of measles-related deaths; 11 countries alone (Afghanistan, Burkina Faso, Democratic Republic of the Congo, Ethiopia, India, Indonesia, Niger, Nigeria, Pakistan, Somalia, Uganda) account for 66% of deaths. This approach quantifies the measles burden by considering country-specific indicators, which can be updated, permitting an assessment of country, regional, and global changes in the burden associated with measles infection.

Organ donation rates in a neurosurgical intensive care unit.

OBJECT: The number of patients waiting for organ transplantation continues to grow, while organs are donated by very few of the thousands of potential donors who die every year. The authors' neurosurgical intensive care unit (NICU) has worked closely with coordinators from the local organ procurement organization (OPO) for many years. In this study, the authors analyze donation rates in the NICU and discuss factors that may be important in maximizing these rates. METHODS: All referrals from the NICU to the OPO from 1996 to 1999 were analyzed. Of the 180 referrals, 98 patients were found to be medically suitable as potential donors. Another 15 patients died of hemodynamic collapse shortly after admission to the NICU. If one assumes that all 15 patients would have been suitable donors, the unsuccessful resuscitation rate becomes 15 (13.3%) of 113. Of the 98 eligible donors, consent was obtained and organs or tissue were recovered in 72, yielding a successful organ procurement rate of 73.5%. CONCLUSIONS: Close working relationships among physicians, nurses, and OPO coordinators can result in higher donation rates than have been reported previously. Aggressive resuscitation and stabilization of all patients, early identification of potential organ donors, prompt declaration of brain death, and attempts by the OPO coordinator to build rapport with families are all important factors that may increase donation rates. Because most organ donors have sustained catastrophic intracranial events, neurosurgeons are uniquely positioned to influence organ donation policies at their hospitals and thus to salvage some benefit from tragic cases of overwhelming brain injury.