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INTRODUCTION: Epilepsy is considered one of the most burdensome neurologic diseases by the World Health Organization due to the high risk of morbidity and mortality. Few studies have investigated the epidemiology of idiopathic epilepsy in Sub-Saharan Africa (SSA). This study aims to characterize the disease burden of epilepsy among the older population in SSA via a large international database. METHODS: Descriptive epidemiological data from the Global Burden of Disease (GBD) database was collected for idiopathic epilepsy in all regions of SSA. The "older" population was defined as 55 years of age and above. The variables of interest included mortality, incidence, prevalence, and disability-adjusted life years (DALYs) rates per one hundred thousand populations. RESULTS: The average mortality rate was highest in Western SSA (6.34 per 100,000), and all regions were significantly higher than the global average (p < 0.001). DALYs and incidence rates of idiopathic epilepsy in all regions of SSA were significantly higher than the global averages (p < 0.01). Globally, the older population had a significantly higher mortality rate than the younger population (2.78 vs 1.62, respectively; p < 0.01). The older population had a higher mortality rate than the younger population in each region of SSA (p < 0.01). Conversely, for DALYs, the younger population had a higher disease burden than the older population globally and in each region of SSA (p < 0.01). CONCLUSION: This study is the first to examine the epidemiologic profile of idiopathic epilepsy in the older population in SSA. Our results indicate that, when compared with the global population, older adults in SSA suffer a greater disease burden and mortality. This study reports the immense need for increased resources and awareness regarding epilepsy in the elderly population of Africa.
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OBJECTIVE: Generalized epileptiform discharges (GEDs) can occur during seizures or without obvious clinical accompaniment. Motor vehicle driving risk during apparently subclinical GEDs is uncertain. Our goals were to develop a feasible, realistic test to evaluate driving safety during GEDs, and to begin evaluating electroencephalographic (EEG) features in relation to driving safety. METHODS: Subjects were aged ≥15 years with generalized epilepsy, GEDs on EEG, and no clinical seizures. Using a high-fidelity driving simulator (miniSim) with simultaneous EEG, a red oval visual stimulus was presented every 5 minutes for baseline testing, and with each GED. Participants were instructed to pull over as quickly and safely as possible with each stimulus. We analyzed driving and EEG signals during GEDs. RESULTS: Nine subjects were tested, and five experienced 88 GEDs total with mean duration 2.31 ± 1.89 (SD) seconds. Of these five subjects, three responded appropriately to all stimuli, one failed to respond to 75% of stimuli, and one stopped driving immediately during GEDs. GEDs with no response to stimuli were significantly longer than those with appropriate responses (8.47 ± 3.10 vs 1.85 ± 0.69 seconds, P < .001). Reaction times to stimuli during GEDs were significantly correlated with GED duration (r = 0.30, P = .04). In addition, EEG amplitude was greater for GEDs with no response to stimuli than GEDs with responses, both for overall root mean square voltage amplitude (66.14 µV vs 52.99 µV, P = .02) and for fractional power changes in the frequency range of waves (P < .05) and spikes (P < .001). SIGNIFICANCE: High-fidelity driving simulation is feasible for investigating driving behavior during GEDs. GEDs with longer duration and greater EEG amplitude showed more driving impairment. Future work with a large sample size may ultimately enable classification of GED EEG features to predict individual driving risk.
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Conducción de Automóvil , Convulsiones/fisiopatología , Entrenamiento Simulado/métodos , Adolescente , Adulto , Electroencefalografía , Estudios de Factibilidad , Femenino , Humanos , Masculino , Proyectos Piloto , Adulto JovenRESUMEN
Generalized spike-wave discharges (SWDs) are the hallmark of generalized epilepsy on the electroencephalogram (EEG). In clinically obvious cases, generalized SWDs produce myoclonic, atonic/tonic, or absence seizures with brief episodes of staring and behavioral unresponsiveness. However, some generalized SWDs have no obvious behavioral effects. A serious challenge arises when patients with no clinical seizures request driving privileges and licensure, yet their EEG shows generalized SWD. Specialized behavioral testing has demonstrated prolonged reaction times or missed responses during SWD, which may present a driving hazard even when patients or family members do not notice any deficits. On the other hand, some SWDs are truly asymptomatic in which case driving privileges should not be restricted. Clinicians often decide on driving privileges based on SWD duration or other EEG features. However, there are currently no empirically-validated guidelines for distinguishing generalized SWDs that are "safe" versus "unsafe" for driving. Here, we review the clinical presentation of generalized SWD and recent work investigating mechanisms of behavioral impairment during SWD with implications for driving safety. As a future approach, computational analysis of large sets of EEG data during simulated driving utilizing machine learning could lead to powerful methods to classify generalized SWD as safe vs. unsafe. This may ultimately provide more objective EEG criteria to guide decisions on driving safety in people with epilepsy.
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Conducción de Automóvil , Electroencefalografía/métodos , Epilepsia Generalizada/fisiopatología , Convulsiones/fisiopatología , Conducción de Automóvil/psicología , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/psicología , Femenino , Humanos , Masculino , Tiempo de Reacción/fisiología , Convulsiones/diagnóstico , Convulsiones/psicologíaRESUMEN
INTRODUCTION: Craniosynostosis is the premature fusion of one or more cranial sutures. The cause of non-syndromic craniosynostosis has been attributed to a complex interaction among genetic, epigenetic, and environmental factors. Increased concordance rates in monozygotic twins support a genetic etiology while a concordance rate less than 100% suggests environmental and/or epigenetic influences. Here, we describe the first reported occurrence of all three children in a triplet set with non-syndromic single-suture craniosynostosis. CASE REPORT: The dichorionic triamniotic triplets were the product of a non-consanguineous marriage delivered at 35 weeks' gestation by a 38-year-old mother and consisted of a monochorionic-diamniotic pair (A and B) and a fraternal triplet (C). Three-dimensional computed tomography scans confirmed sagittal synostosis in A and B and metopic synostosis in C. All patients underwent endoscopic strip craniectomy and were discharged on the second postoperative day with helmet orthoses. Comparative genetic hybridization (CGH) and whole-exome sequencing (WES) failed to identify pathogenic copy number variants or gene mutations, respectively. DISCUSSION AND CONCLUSION: The results of the genetic testing suggest the possibility of a rare variant contributing to the risk of midline craniosynostosis shared among the triplets, with potential modifiers at other genetic loci affecting the phenotype. We speculate mutations at loci within non-coding regions not captured by our genetic analysis may have been involved. Moreover, epigenetic factors as well as environmental factors including, but not limited to, in utero head constraint could have contributed to the observed phenotype.
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Craneosinostosis , Craneosinostosis/cirugía , Craneotomía/métodos , Femenino , Humanos , Masculino , Embarazo , Embarazo TripleRESUMEN
OBJECTIVE: Despite advances in the nonsurgical management of cerebrovascular atherosclerotic steno-occlusive disease, approximately 15-20% of patients remain at high risk for recurrent ischemia. The benefit of revascularization with flow augmentation bypass has been demonstrated in studies of Moyamoya vasculopathy. Unfortunately, there are mixed results for the use of flow augmentation in atherosclerotic cerebrovascular disease. We conducted a study to examine the efficacy and long term outcomes of superficial temporal artery to middle cerebral artery (STA-MCA) bypass in patients with recurrent ischemia despite optimal medical management. METHODS: A single-institution retrospective review of patients receiving flow augmentation bypass from 2013-2021 was conducted. Patients with non-Moyamoya vaso-occlusive disease (VOD) who had continued ischemic symptoms or strokes despite best medical management were included. The primary outcome was time to post-operative stroke. Time from cerebrovascular accident to surgery, complications, imaging results, and modified Rankin Scale (mRS) scores were aggregated. RESULTS: Twenty patients met inclusion criteria. The median time from cerebrovascular accident to surgery was 87 (28-105.0) days. Only one patient (5%) had a stroke at 66 days post-op. One (5%) patient had a post-operative scalp infection, while 3 (15%) developed post-operative seizures. All 20 (100%) bypasses remained patent at follow-up. The median mRS score at follow up was significantly improved from presentation from 2.5 (1-3) to 1 (0-2), P = .013. CONCLUSIONS: For patients with high-risk non-Moyamoya VOD who have failed optimal medical therapy, contemporary approaches to flow augmentation with STA-MCA bypass may prevent future ischemic events with a low complication rate.
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Aterosclerosis , Revascularización Cerebral , Enfermedad de Moyamoya , Accidente Cerebrovascular , Cirujanos , Humanos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/cirugía , Enfermedad de Moyamoya/complicaciones , Enfermedad de Moyamoya/cirugía , Aterosclerosis/complicaciones , Aterosclerosis/cirugía , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Arteria Cerebral Media/cirugía , Arterias Temporales , Revascularización Cerebral/métodos , Resultado del Tratamiento , Circulación CerebrovascularRESUMEN
Absence seizures are brief episodes of impaired consciousness, behavioral arrest, and unresponsiveness, with yet-unknown neuronal mechanisms. Here we report that an awake female rat model recapitulates the behavioral, electroencephalographic, and cortical functional magnetic resonance imaging characteristics of human absence seizures. Neuronally, seizures feature overall decreased but rhythmic firing of neurons in cortex and thalamus. Individual cortical and thalamic neurons express one of four distinct patterns of seizure-associated activity, one of which causes a transient initial peak in overall firing at seizure onset, and another which drives sustained decreases in overall firing. 40-60 s before seizure onset there begins a decline in low frequency electroencephalographic activity, neuronal firing, and behavior, but an increase in higher frequency electroencephalography and rhythmicity of neuronal firing. Our findings demonstrate that prolonged brain state changes precede consciousness-impairing seizures, and that during seizures distinct functional groups of cortical and thalamic neurons produce an overall transient firing increase followed by a sustained firing decrease, and increased rhythmicity.
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Estado de Conciencia , Epilepsia Tipo Ausencia , Femenino , Ratas , Humanos , Animales , Estado de Conciencia/fisiología , Roedores , Convulsiones , Tálamo , Electroencefalografía/métodos , Neuronas/fisiología , Corteza CerebralRESUMEN
BACKGROUND: Individuals with COVID-19 experience thrombotic events probably due to the associated hypofibrinolysis resulting from the upregulation of plasminogen activator inhibitor-1 (PAI-1) antigen. This study evaluated plasma PAI-1 antigen levels and haematological parameters before treatment and after recovery from severe COVID-19 in Ghana. MATERIALS AND METHODS: This cross-sectional study was conducted at Sunyani Regional Hospital, and recruited 51 patients who had RT-PCR-confirmed SARS-CoV-2. Participants' sociodemographic data and clinical characteristics were taken from the hospital records. Venous blood was taken before COVID-19 treatment commenced for FBC, PAI-1 and ferritin assays. FBC was assessed using an automated haematology analyzer, whilst plasma PAI-1 Ag and serum ferritin levels were assessed with sandwich ELISA. All the tests were repeated immediately after participants recovered from COVID-19. RESULTS: Of the 51 participants recruited into the study, 78.4% (40) had non-severe COVID-19 whiles 21.6% (11) experienced a severe form of the disease. Severe COVID-19 participants had significantly lower haemoglobin (g/dL): 8.1 (7.3-8.4) vs 11.8 (11.0-12.5), p<0.001; RBC x 1012/L: 2.9 (2.6-3.1) vs 3.4 (3.1-4.3), p = 0.001; HCT%: 24.8 ± 2.6 vs 35.3 ± 6.7, p<0.001 and platelet x 109/L: 86.4 (62.2-91.8) vs 165.5 (115.1-210.3), p<0.001, compared with the non-severe COVID-19 group. But WBC x 109/L: 11.6 (9.9-14.2) vs 5.4 (3.7-6.6), p<0.001 and ferritin (ng/mL): 473.1 (428.3-496.0) vs 336.2 (249.9-386.5), p<0.001, were relatively higher in the participants with severe COVID-19 than the non-severe COVID-19 counterparts. Also, the severely ill SARS-CoV-2-infected participants had relatively higher plasma PAI-1 Ag levels (ng/mL): 131.1 (128.7-131.9) vs 101.3 (92.0-116.8), p<0.001, than those with the non-severe form of the disease. Participants had lower haemoglobin (g/dL): 11.4 (8.8-12.3 vs 12.4 (11.5-13.6), p<0.001; RBC x 1012/L: 3.3 (2.9-4.0) vs 4.3 (3.4-4.6), p = 0.001; absolute granulocyte count x 109/L: 2.3 ± 1.0 vs 4.6 ± 1.8, p<0.001, and platelet x 109/L: 135.0 (107.0-193.0) vs 229.0 (166.0-270.0), p<0.001 values at admission before treatment commenced, compared to when they recovered from the disease. Additionally, the median PAI-1 Ag (ng/mL): 89.6 (74.9-100.8) vs 103.1 (93.2-128.7), p<0.001 and ferritin (ng/mL): 242.2 (197.1-302.1) vs 362.3 (273.1-399.9), p<0.001 levels were reduced after a successful recovery from COVID-19 compared to the values at admission. CONCLUSION: Plasma PAI-1 Ag level was higher among severe COVID-19 participants. The COVID-19-associated inflammation could affect red blood cell parameters and platelets. Successful recovery from COVID-19, with reduced inflammatory response as observed in the decline of serum ferritin levels restores the haematological parameters. Plasma levels of PAI-1 should be assessed during the management of severe COVID-19 in Ghana. This will enhance the early detection of probable thrombotic events and prompts Physicians to provide interventions to prevent thrombotic complications associated with COVID-19.
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Hydrocephalus is the most common neurosurgical disorder worldwide and is characterized by enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles resulting from failed CSF homeostasis. Since the 1840s, physicians have observed inflammation in the brain and the CSF spaces in both posthaemorrhagic hydrocephalus (PHH) and postinfectious hydrocephalus (PIH). Reparative inflammation is an important protective response that eliminates foreign organisms, damaged cells and physical irritants; however, inappropriately triggered or sustained inflammation can respectively initiate or propagate disease. Recent data have begun to uncover the molecular mechanisms by which inflammation - driven by Toll-like receptor 4-regulated cytokines, immune cells and signalling pathways - contributes to the pathogenesis of hydrocephalus. We propose that therapeutic approaches that target inflammatory mediators in both PHH and PIH could address the multiple drivers of disease, including choroid plexus CSF hypersecretion, ependymal denudation, and damage and scarring of intraventricular and parenchymal (glia-lymphatic) CSF pathways. Here, we review the evidence for a prominent role of inflammation in the pathogenic mechanism of PHH and PIH and highlight promising targets for therapeutic intervention. Focusing research efforts on inflammation could shift our view of hydrocephalus from that of a lifelong neurosurgical disorder to that of a preventable neuroinflammatory condition.
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Encefalitis/tratamiento farmacológico , Hidrocefalia/complicaciones , Animales , Encefalitis/etiología , Encefalitis/patología , Humanos , Mediadores de InflamaciónRESUMEN
BACKGROUND: Research experience is believed to be an important component of the neurosurgery residency application process. One measure of research productivity is publication volume. The preresidency publication volume of U.S. neurosurgery interns and any potential association between applicant publication volume and the match results of top-ranked residency programs have not been well characterized. OBJECTIVE: In this study, we sought to characterize the preresidency publication volume of U.S. neurosurgery residents in the 2018-2019 intern class using the Scopus database. METHODS: For each intern, we recorded the total number of publications, total number of first or last author publications, total number of neuroscience-related publications, mean number of citations per publication, and mean impact factor of the journal per publication. Preresidency publication volumes of interns at the top-25 programs (based on a composite ranking score according to 4 different ranking metrics) were compared with those at all other programs. RESULTS: We found that 82% of neurosurgery interns included in the analysis (190 interns from 95 programs) had at least 1 publication. The average number of publications per intern among all programs was 6 ± 0.63 (mean ± standard error of the mean). We also found that interns at top-25 neurosurgery residency programs tended to have a higher number of publications (8.3 ± 1.2 vs. 4.8 ± 0.7, P = 0.0137), number of neuroscience-related publications (6.8 ± 1.1 vs. 4.1 ± 0.7, P = 0.0419), and mean number of citations per publication (9.8 ± 1.7 vs. 5.7 ± 0.8, P = 0.0267) compared with interns at all other programs. CONCLUSIONS: Our results provide a general estimate of the preresidency publication volume of U.S. neurosurgery interns and suggest a potential association between publication volume and matching in the top-25 neurosurgery residency programs.
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Eficiencia , Internado y Residencia , Neurocirugia/educación , Publicaciones/estadística & datos numéricos , Humanos , Estados UnidosRESUMEN
BACKGROUND: "White cord syndrome" is a very rare condition thought to be due to acute reperfusion of chronically ischemic areas of the spinal cord. Its hallmark is the presence of intramedullary hyperintense signal on T2-weighted magnetic resonance imaging sequences in a patient with unexplained neurologic deficits following spinal cord decompression surgery. The syndrome is rare and has been reported previously in 2 patients following anterior cervical decompression and fusion. We report an additional case of this complication. CASE DESCRIPTION: A 68-year-old man developed acute left-sided hemiparesis after posterior cervical decompression and fusion for cervical spondylotic myelopathy. The patient improved with high-dose steroid therapy. CONCLUSIONS: The rare white cord syndrome following either anterior cervical decompression and fusion or posterior cervical decompression and fusion may be due to ischemic-reperfusion injury sustained by chronically compressed parts of the spinal cord. In previous reports, patients have improved following steroid therapy and acute rehabilitation.
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Vértebras Cervicales/cirugía , Descompresión Quirúrgica/efectos adversos , Paresia/etiología , Complicaciones Posoperatorias/etiología , Fusión Vertebral/efectos adversos , Estenosis Espinal/cirugía , Enfermedad Aguda , Anciano , Vértebras Cervicales/diagnóstico por imagen , Humanos , Masculino , Paresia/diagnóstico por imagen , Paresia/rehabilitación , Modalidades de Fisioterapia , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/rehabilitación , Estenosis Espinal/diagnóstico por imagen , SíndromeRESUMEN
Campomelic dysplasia is a rare skeletal dysplasia characterized by Pierre Robin sequence, craniofacial dysmorphism, shortening and angulation of long bones, tracheobronchomalacia, and occasionally sex reversal. The disease is due to mutations in SOX9 or chromosomal rearrangements involving the long arm of Chromosome 17 harboring the SOX9 locus. SOX9, a transcription factor, is indispensible in establishing and maintaining neural stem cells in the central nervous system. We present a patient with angulation of long bones and external female genitalia on prenatal ultrasound who was subsequently found to harbor the chromosomal abnormality 46, XY, t(6;17) (p21.1;q24.3) on prenatal genetic testing. Comparative genomic hybridization revealed deletions at 6p21.1 and 17q24.3, the latter being 2.3 Mb upstream of SOX9 Whole-exome sequencing did not identify pathogenic variants in SOX9, suggesting that the 17q24.3 deletion represents a translocation breakpoint farther upstream of SOX9 than previously identified. At 2 mo of age the patient developed progressive communicating ventriculomegaly and thinning of the cortical mantle without clinical signs of increased intracranial pressure. This case suggests ventriculomegaly in some cases represents not a primary impairment of cerebrospinal fluid dynamics, but an epiphenomenon driven by a genetic dysregulation of neural progenitor cell fate.
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Displasia Campomélica/diagnóstico , Displasia Campomélica/genética , Hidrocefalia/diagnóstico , Hidrocefalia/genética , Fenotipo , Factor de Transcripción SOX9/genética , Translocación Genética , Encéfalo/anomalías , Encéfalo/diagnóstico por imagen , Hibridación Genómica Comparativa , Femenino , Estudios de Asociación Genética , Mutación de Línea Germinal , Humanos , Hibridación Fluorescente in Situ , Recién Nacido , Imagen por Resonancia Magnética , Esqueleto/anomalías , Esqueleto/diagnóstico por imagen , Médula Espinal/anomalías , Médula Espinal/diagnóstico por imagenRESUMEN
Hydrocephalus, a disorder of impaired cerebrospinal fluid (CSF) homeostasis, often results from an imbalance between CSF production and reabsorption. Rarely, hydrocephalus is the consequence of CSF hypersecretion in the context of diffuse villous hyperplasia of the choroid plexus (DVHCP). The limited genetic information in previously reported cases suggests a high prevalence of gains of Chromosome 9p in this disease, although the critical genes involved in DVHCP pathogenesis have not been identified. Here, we report a patient with syndromic hydrocephalus with DVHCP associated with a novel 9p24.3-11.2 triplication and 15q13.2-q13.3 microdeletion. We review the clinical, radiological, and pathological features of DVHCP, as well as its surgical management. A better understanding of the genetic basis of DVHCP could spur the development of rational, targeted nonsurgical hydrocephalus treatments.
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Plexo Coroideo/patología , Cromosomas Humanos Par 9/genética , Hidrocefalia/genética , Derivaciones del Líquido Cefalorraquídeo , Duplicación de Gen/genética , Humanos , Hiperplasia/genética , Lactante , Ventrículos Laterales , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos XRESUMEN
Congenital hemangiomas are tumor-like vascular malformations with poorly understood pathogenesis. We report the case of a neonate with a massive congenital scalp hemangioma that required urgent neurosurgical removal on the second day of life because of concern for high-flow arteriovenous shunting. Exome sequencing identified a rare damaging de novo germline mutation in MYH9 (c.5308C>T, p.[Arg1770Cys]), encoding the MYH9 nonmuscle myosin IIA. MYH9 has a probability of loss-of-function intolerance (pLI) score of >0.99 and is highly intolerant to missense variation (z score = 5.59). The p.(Arg1770Cys) mutation substitutes an evolutionarily conserved amino acid in the protein's critical myosin tail domain and is predicted to be highly deleterious by SIFT, PolyPhen-2, MetaSVM, and CADD. MYH9 is a known regulator of cytokinesis, VEGF-regulated angiogenesis, and p53-dependent tumorigenesis. These findings reveal a novel association of germline de novo MYH9 mutation with congenital hemangioma.
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Hemangioma/genética , Proteínas Motoras Moleculares/genética , Cadenas Pesadas de Miosina/genética , Neoplasias Cutáneas/genética , Femenino , Mutación de Línea Germinal , Hemangioma/patología , Humanos , Recién Nacido , Mutación con Pérdida de Función , Cuero Cabelludo/patología , Neoplasias Cutáneas/patologíaRESUMEN
Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted mutations: TRIM71 (p = 2.15 × 10-7), SMARCC1 (p = 8.15 × 10-10), and PTCH1 (p = 1.06 × 10-6). Additionally, two de novo duplications were identified at the SHH locus, encoding the PTCH1 ligand (p = 1.2 × 10-4). Together, these probands account for â¼10% of studied cases. Strikingly, all four genes are required for neural tube development and regulate ventricular zone neural stem cell fate. These results implicate impaired neurogenesis (rather than active CSF accumulation) in the pathogenesis of a subset of CH patients, with potential diagnostic, prognostic, and therapeutic ramifications.