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Generalized onset seizures with focal evolution (GOFE) - A unique seizure type in the setting of generalized epilepsy.
Linane A, Lagrange AH, Fu C, Abou-Khalil B
(2016) Epilepsy Behav 54: 20-9
MeSH Terms: Adolescent, Anticonvulsants, Brain, Child, Child, Preschool, Disease Progression, Electroencephalography, Epilepsies, Partial, Epilepsy, Generalized, Female, Humans, Male, Neurologic Examination, Risk Factors, Seizures
Show Abstract · Added March 14, 2018
PURPOSE - We report clinical and electrographic features of generalized onset seizures with focal evolution (GOFE) and present arguments for the inclusion of this seizure type in the seizure classification.
METHODS - The adult and pediatric Epilepsy Monitoring Unit databases at Vanderbilt Medical Center and Children's Hospital were screened to identify generalized onset seizures with focal evolution. We reviewed medical records for epilepsy characteristics, epilepsy risk factors, MRI abnormalities, neurologic examination, antiepileptic medications before and after diagnosis, and response to medications. We also reviewed ictal and interictal EEG tracings, as well as video-recorded semiology.
RESULTS - Ten patients were identified, 7 males and 3 females. All of the patients developed generalized epilepsy in childhood or adolescence (ages 3-15years). Generalized onset seizures with focal evolution developed years after onset in 9 patients, with a semiology concerning for focal seizures or nonepileptic events. Ictal discharges had a generalized onset on EEG, described as either generalized spike-and-wave and/or polyspike-and-wave discharges, or generalized fast activity. This electrographic activity then evolved to focal rhythmic activity most commonly localized to one temporal or frontal region; five patients had multiple seizures evolving to focal activity in different regions of both hemispheres. The predominant interictal epileptiform activity included generalized spike-and-wave and/or polyspike-and-wave discharges in all patients. Taking into consideration all clinical and EEG data, six patients were classified with genetic (idiopathic) generalized epilepsy, and four were classified with structural/metabolic (symptomatic) generalized epilepsy. All of the patients had modifications to their medications following discharge, with three becoming seizure-free and five responding with >50% reduction in seizure frequency.
CONCLUSION - Generalized onset seizures may occasionally have focal evolution with semiology suggestive of focal seizures, leading to a misdiagnosis of focal onset. This unique seizure type may occur with genetic as well as structural/metabolic forms of epilepsy. The identification of this seizure type may help clinicians choose appropriate medications, avoiding narrow spectrum agents known to aggravate generalized onset seizures.
Copyright © 2015 Elsevier Inc. All rights reserved.
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15 MeSH Terms
Genetic risk for Parkinson's disease correlates with alterations in neuronal manganese sensitivity between two human subjects.
Aboud AA, Tidball AM, Kumar KK, Neely MD, Ess KC, Erikson KM, Bowman AB
(2012) Neurotoxicology 33: 1443-1449
MeSH Terms: Biosensing Techniques, Case-Control Studies, Cell Line, Cell Survival, Chlorides, Dose-Response Relationship, Drug, Environmental Pollutants, Gene-Environment Interaction, Genetic Predisposition to Disease, Humans, Induced Pluripotent Stem Cells, Manganese Compounds, Manganese Poisoning, Membrane Potential, Mitochondrial, Mitochondria, Mutation, Neural Stem Cells, Neurologic Examination, Parkinson Disease, Parkinson Disease, Secondary, Phenotype, Reactive Oxygen Species, Risk Factors, Time Factors, Ubiquitin-Protein Ligases
Show Abstract · Added August 25, 2013
Manganese (Mn) is an environmental risk factor for Parkinson's disease (PD). Recessive inheritance of PARK2 mutations is strongly associated with early onset PD (EOPD). It is widely assumed that the influence of PD environmental risk factors may be enhanced by the presence of PD genetic risk factors in the genetic background of individuals. However, such interactions may be difficult to predict owing to the complexities of genetic and environmental interactions. Here we examine the potential of human induced pluripotent stem (iPS) cell-derived early neural progenitor cells (NPCs) to model differences in Mn neurotoxicity between a control subject (CA) with no known PD genetic risk factors and a subject (SM) with biallelic loss-of-function mutations in PARK2 and family history of PD but no evidence of PD by neurological exam. Human iPS cells were generated from primary dermal fibroblasts of both subjects. We assessed several outcome measures associated with Mn toxicity and PD. No difference in sensitivity to Mn cytotoxicity or mitochondrial fragmentation was observed between SM and CA NPCs. However, we found that Mn exposure was associated with significantly higher reactive oxygen species (ROS) generation in SM compared to CA NPCs despite significantly less intracellular Mn accumulation. Thus, this report offers the first example of human subject-specific differences in PD-relevant environmental health related phenotypes that are consistent with pathogenic interactions between known genetic and environmental risk factors for PD.
Copyright © 2012 Elsevier Inc. All rights reserved.
2 Communities
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25 MeSH Terms
Decreasing adrenergic or sympathetic hyperactivity after severe traumatic brain injury using propranolol and clonidine (DASH After TBI Study): study protocol for a randomized controlled trial.
Patel MB, McKenna JW, Alvarez JM, Sugiura A, Jenkins JM, Guillamondegui OD, Pandharipande PP
(2012) Trials 13: 177
MeSH Terms: Adrenergic Fibers, Adrenergic alpha-2 Receptor Agonists, Adrenergic beta-Antagonists, Biomarkers, Brain Injuries, Catecholamines, Clonidine, Cognition, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Glasgow Coma Scale, Hemodynamics, Humans, Neurologic Examination, Neuropsychological Tests, Propranolol, Quality of Life, Research Design, Sympathetic Nervous System, Tennessee, Time Factors, Treatment Outcome
Show Abstract · Added June 14, 2016
BACKGROUND - Severe TBI, defined as a Glasgow Coma Scale ≤ 8, increases intracranial pressure and activates the sympathetic nervous system. Sympathetic hyperactivity after TBI manifests as catecholamine excess, hypertension, abnormal heart rate variability, and agitation, and is associated with poor neuropsychological outcome. Propranolol and clonidine are centrally acting drugs that may decrease sympathetic outflow, brain edema, and agitation. However, there is no prospective randomized evidence available demonstrating the feasibility, outcome benefits, and safety for adrenergic blockade after TBI.
METHODS/DESIGN - The DASH after TBI study is an actively accruing, single-center, randomized, double-blinded, placebo-controlled, two-arm trial, where one group receives centrally acting sympatholytic drugs, propranolol (1 mg intravenously every 6 h for 7 days) and clonidine (0.1 mg per tube every 12 h for 7 days), and the other group, double placebo, within 48 h of severe TBI. The study uses a weighted adaptive minimization randomization with categories of age and Marshall head CT classification. Feasibility will be assessed by ability to provide a neuroradiology read for randomization, by treatment contamination, and by treatment compliance. The primary endpoint is reduction in plasma norepinephrine level as measured on day 8. Secondary endpoints include comprehensive plasma and urine catecholamine levels, heart rate variability, arrhythmia occurrence, infections, agitation measures using the Richmond Agitation-Sedation Scale and Agitated Behavior scale, medication use (anti-hypertensive, sedative, analgesic, and antipsychotic), coma-free days, ventilator-free days, length of stay, and mortality. Neuropsychological outcomes will be measured at hospital discharge and at 3 and 12 months. The domains tested will include global executive function, memory, processing speed, visual-spatial, and behavior. Other assessments include the Extended Glasgow Outcome Scale and Quality of Life after Brain Injury scale. Safety parameters evaluated will include cardiac complications.
DISCUSSION - The DASH After TBI Study is the first randomized, double-blinded, placebo-controlled trial powered to determine feasibility and investigate safety and outcomes associated with adrenergic blockade in patients with severe TBI. If the study results in positive trends, this could provide pilot evidence for a larger multicenter randomized clinical trial. If there is no effect of therapy, this trial would still provide a robust prospective description of sympathetic hyperactivity after TBI.
TRIAL REGISTRATION - ClinicalTrials.gov NCT01322048.
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23 MeSH Terms
Long-term outcomes of group B streptococcal meningitis.
Libster R, Edwards KM, Levent F, Edwards MS, Rench MA, Castagnini LA, Cooper T, Sparks RC, Baker CJ, Shah PE
(2012) Pediatrics 130: e8-15
MeSH Terms: Child, Child, Preschool, Developmental Disabilities, Female, Follow-Up Studies, Hearing Disorders, Hearing Tests, Humans, Infant, Learning Disabilities, Logistic Models, Male, Meningitis, Bacterial, Multivariate Analysis, Neurologic Examination, Psychological Tests, Streptococcal Infections, Streptococcus agalactiae, Vision Disorders, Vision Screening
Show Abstract · Added May 28, 2014
OBJECTIVE - Group B Streptococcus (GBS) is the leading cause of meningitis in young infants. We evaluated long-term outcomes among GBS meningitis survivors. We hypothesized that despite reduced mortality, GBS meningitis would remain a significant cause of morbidity among GBS survivors.
METHODS - Ninety term and near-term infants diagnosed with GBS meningitis from 1998 through 2006 were identified from 2 children's hospitals. Five died acutely, and 5 died at 6 months to 3 years of age. Forty-three survivors (54%; mean age 6.8, range 3-12 years) were consented for evaluation and underwent physical and neurologic examinations, hearing and vision screening, and standardized developmental assessments. Associations among presenting features, laboratory parameters, neurologic status at hospital discharge, and later developmental outcomes were explored by using descriptive statistics and logistic regression.
RESULTS - Twenty-four of 43 (56%) children evaluated demonstrated age-appropriate development, 11 (25%) had mild-to-moderate impairment, and 8 (19%) had severe impairment. Admission features associated with death after hospital discharge or severe impairment included lethargy (P = .003), respiratory distress (P = .022), coma or semicoma (P = .022), seizures (P = .015), bulging fontanel (P = .034), leukopenia (P = .026), acidosis (P = .024), cerebrospinal fluid protein >300 mg/dL (P = .006), cerebrospinal fluid glucose <20 mg/dL (P = .026), and need for ventilator (P = .002) or pressor support (P < .001). Features at discharge associated with late death or severe impairment included failed hearing screen (P = .004), abnormal neurologic examination (P < .001), and abnormal end of therapy brain imaging (P = .038).
CONCLUSIONS - Survivors of GBS meningitis continue to have substantial long-term morbidity, highlighting the need for ongoing developmental follow-up and prevention strategies such as maternal immunization.
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20 MeSH Terms
Deep brain stimulation in early stage Parkinson's disease: operative experience from a prospective randomised clinical trial.
Kahn E, D'Haese PF, Dawant B, Allen L, Kao C, Charles PD, Konrad P
(2012) J Neurol Neurosurg Psychiatry 83: 164-70
MeSH Terms: Aged, Deep Brain Stimulation, Disease Progression, Electrodes, Implanted, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neurologic Examination, Neurosurgical Procedures, Parkinson Disease, Perioperative Period, Postoperative Complications, Prospective Studies, Retrospective Studies, Speech Disorders, Stroke, Subthalamic Nucleus
Show Abstract · Added April 10, 2018
BACKGROUND - Recent evidence suggests that deep brain stimulation of the subthalamic nucleus (STN-DBS) may have a disease modifying effect in early Parkinson's disease (PD). A randomised, prospective study is underway to determine whether STN-DBS in early PD is safe and tolerable.
OBJECTIVES/METHODS - 15 of 30 early PD patients were randomised to receive STN-DBS implants in an institutional review board approved protocol. Operative technique, location of DBS leads and perioperative adverse events are reported. Active contact used for stimulation in these patients was compared with 47 advanced PD patients undergoing an identical procedure by the same surgeon.
RESULTS - 14 of the 15 patients did not sustain any long term (>3 months) complications from the surgery. One subject suffered a stroke resulting in mild cognitive changes and slight right arm and face weakness. The average optimal contact used in symptomatic treatment of early PD patients was: anterior -1.1±1.7 mm, lateral 10.7±1.7 mm and superior -3.3±2.5 mm (anterior and posterior commissure coordinates). This location is statistically no different (0.77 mm, p>0.05) than the optimal contact used in the treatment of 47 advanced PD patients.
CONCLUSIONS - The perioperative adverse events in this trial of subjects with early stage PD are comparable with those reported for STN-DBS in advanced PD. The active contact position used in early PD is not significantly different from that used in late stage disease. This is the first report of the operative experience from a randomised, surgical versus best medical therapy trial for the early treatment of PD.
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MeSH Terms
Pediatric cerebellar pilomyxoid-spectrum astrocytomas.
Forbes JA, Mobley BC, O'Lynnger TM, Cooper CM, Ghiassi M, Hanif R, Pearson MM
(2011) J Neurosurg Pediatr 8: 90-6
MeSH Terms: Astrocytoma, Cerebellar Neoplasms, Cerebellum, Cerebral Ventricle Neoplasms, Chemotherapy, Adjuvant, Child, Preschool, Combined Modality Therapy, Cranial Fossa, Posterior, Craniotomy, Diffusion Magnetic Resonance Imaging, Disease Progression, Dissection, Female, Fourth Ventricle, Humans, Infant, Magnetic Resonance Imaging, Meninges, Neoplasm Invasiveness, Neoplasm Recurrence, Local, Neurologic Examination, Skull Base Neoplasms
Show Abstract · Added August 14, 2014
OBJECT - Pediatric cerebellar astrocytomas with pilomyxoid features include classic pilomyxoid astrocytomas (PMAs) and intermediate pilomyxoid tumors (IPTs). Since the original description of PMA in 1999, most reports in the literature have described PMAs arising from the hypothalamic/chiasmatic region. To the authors' knowledge, PMAs arising from the posterior fossa have not been discussed in the neurosurgical literature. Intermediate pilomyxoid tumors, or tumors with pathological features of both pilocytic astrocytoma (PA) and PMA, have only recently been described. In this article, the authors present 2 cases that fall within the spectrum of pediatric cerebellar PMA-including a classic PMA and an intermediate pilomyxoid tumor. The authors compare the radiological presentation, surgical results, and postoperative course to findings in a cohort of 15 patients with cerebellar PAs.
METHODS - Between 2003 and 2010, 2 patients with pilomyxoid-spectrum astrocytomas underwent treatment at Vanderbilt Children's Hospital. One was a 22-month-old girl who presented with progressive gait disturbance and falls. The other was a 4-year-old girl who presented with ataxia and generalized weakness. In a retrospective review of pediatric cerebellar neoplasms resected by the senior author during this period, these tumors comprised 4% of cerebellar neoplasms and approximately 10% of cerebellar glial neoplasms.
RESULTS - Both patients were treated with midline suboccipital craniotomy for resection. In both cases, tumor invasion anteriorly into the brainstem prevented gross-total resection. the patient in Case 1 was placed on chemotherapy following pathological diagnosis and later developed definitive evidence of leptomeningeal dissemination (LD) 3 years after the operation. The patient in Case 2 was placed on chemotherapy after exhibiting progressive evidence of local recurrence (findings were negative for LD) 12 months following resection.
CONCLUSIONS - Pediatric patients with cerebellar pilomyxoid-spectrum astrocytomas appear to suffer higher rates of local recurrence and LD than pediatric patients with cerebellar PAs.
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22 MeSH Terms
Brain structure and cerebrovascular risk in cognitively impaired patients: Shanghai Community Brain Health Initiative-pilot phase.
He J, Iosif AM, Lee DY, Martinez O, Chu S, Carmichael O, Mortimer JA, Zhao Q, Ding D, Guo Q, Galasko D, Salmon DP, Dai Q, Wu Y, Petersen RC, Hong Z, Borenstein AR, DeCarli C
(2010) Arch Neurol 67: 1231-7
MeSH Terms: Aged, Brain, Cerebrovascular Disorders, China, Cognition Disorders, Cross-Sectional Studies, Dementia, Female, Humans, Logistic Models, Magnetic Resonance Imaging, Male, Middle Aged, Neurologic Examination, Neuropsychological Tests, Odds Ratio, Physical Examination, Retrospective Studies, Risk Factors, Urban Population
Show Abstract · Added March 5, 2014
OBJECTIVE - To investigate the associations among brain morphologic changes as seen on magnetic resonance imaging (MRI), cerebrovascular risk (CVR), and clinical diagnosis and cognition in elderly patients with mild cognitive impairment and dementia living in urban Shanghai.
DESIGN - Cross-sectional study performed from May 1, 2007, to November 31, 2008.
SETTING - Memory Disorders Clinic of the Huashan Hospital and the Shanghai community.
PARTICIPANTS - Ninety-six older people: 32 with normal cognition (NC), 30 with amnestic mild cognitive impairment (aMCI), and 34 with dementia.
MAIN OUTCOME MEASURES - For each patient, we administered a neurologic and physical examination, neuropsychological evaluation, and brain MRI and genotyped the apolipoprotein E-ε4 (APOE-ε4) gene. The volumes determined by MRI were assessed using a semiautomatic method.
RESULTS - Brain volume was significantly smaller in the dementia patients compared with the NC (P < .001) and aMCI patients (P = .04). Hippocampal volume (HV) was lower and white matter hyperintensity (WMH) volume was higher in those with aMCI (HV: P = .03; WMH volume: P = .04) and dementia (HV: P < .001; WMH volume: P = .002) compared with NC participants. The presence of APOE-ε4 was significantly associated with reduced HV (P = .02). Systolic blood pressure was positively associated with CVR score (P = .04); diastolic blood pressure (P = .02) and CVR score (P = .04) were positively associated with WMH volume. The WMH volume (P = .03) and CVR score (P = .03) were higher among dementia patients compared with NC participants.
CONCLUSIONS - Brain structure changes seen on MRI were significantly associated with clinical diagnosis. In addition, blood pressure was highly associated with CVR score and WMH volume. These results suggest that MRI is a valuable measure of brain injury in a Chinese cohort and can serve to assess the effects of various degenerative and cerebrovascular diseases.
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20 MeSH Terms
Early neurologic abnormalities associated with human T-cell lymphotropic virus type 1 infection in a cohort of Peruvian children.
Kendall EA, González E, Espinoza I, Tipismana M, Verdonck K, Clark D, Vermund SH, Gotuzzo E
(2009) J Pediatr 155: 700-6
MeSH Terms: Adolescent, Age Distribution, Age of Onset, Case-Control Studies, Child, Child, Preschool, Cohort Studies, Confidence Intervals, Female, HTLV-I Infections, Human T-lymphotropic virus 1, Humans, Infectious Disease Transmission, Vertical, Male, Neurologic Examination, Odds Ratio, Paraparesis, Paraparesis, Tropical Spastic, Peru, Prevalence, Probability, Risk Assessment, Severity of Illness Index, Sex Distribution, Spinal Cord Diseases, Time Factors, Urination Disorders
Show Abstract · Added March 5, 2014
OBJECTIVE - Because human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) may occur in some children infected with HTLV-1, we sought to determine the prevalence of neurologic abnormalities and any associations of neurologic abnormalities with infective dermatitis in these children.
STUDY DESIGN - We enrolled 58 children infected with HTLV-1 and 42 uninfected children (ages 3 to 17) of mothers infected with HTLV-1 in a family study in Lima, Peru. We obtained medical and developmental histories, surveyed current neurologic symptoms, and conducted a standardized neurologic examination without prior knowledge of HTLV-1 status.
RESULTS - HTLV-1 infection was associated with reported symptoms of lower extremity weakness/fatigue (odds ratio [OR], 6.1; confidence interval [CI], 0.7 to 281), lumbar pain (OR, 1.7; 95% CI, 0.4 to 8), and paresthesia/dysesthesia (OR, 2.6; CI, 0.6 to 15.8). HTLV-1 infection was associated with lower-extremity hyperreflexia (OR, 3.1; CI, 0.8 to 14.2), ankle clonus (OR, 5.0; CI, 1.0 to 48.3), and extensor plantar reflex (OR undefined; P = .2). Among children infected with HTLV-1, a history of infective dermatitis was associated with weakness (OR, 2.7; CI, 0.3 to 33), lumbar pain (OR, 1.3; CI, 0.2 to 8), paresthesia/dysesthesia (OR, 2.9; CI, 0.5 to 20), and urinary disturbances (OR, 5.7; CI, 0.5 to 290).
CONCLUSIONS - Abnormal neurologic findings were common in Peruvian children infected with HTLV-1, and several findings were co-prevalent with infective dermatitis. Pediatricians should monitor children infected with HTLV-1 for neurologic abnormalities.
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27 MeSH Terms
AHA/ACCF Scientific Statement on the evaluation of syncope: from the American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, and the Quality of Care and Outcomes Research Interdisciplinary Working Group; and the American College of Cardiology Foundation: in collaboration with the Heart Rhythm Society: endorsed by the American Autonomic Society.
Strickberger SA, Benson DW, Biaggioni I, Callans DJ, Cohen MI, Ellenbogen KA, Epstein AE, Friedman P, Goldberger J, Heidenreich PA, Klein GJ, Knight BP, Morillo CA, Myerburg RJ, Sila CA, American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, Quality of Care and Outcomes Research Interdisciplinary Working Group, American College of Cardiology Foundation, Heart Rhythm Society, American Autonomic Society
(2006) Circulation 113: 316-27
MeSH Terms: Adult, Aged, Child, Electrocardiography, Electrophysiologic Techniques, Cardiac, Heart Diseases, Humans, Neurologic Examination, Syncope
Added December 10, 2013
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9 MeSH Terms
AHA/ACCF scientific statement on the evaluation of syncope: from the American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, and the Quality of Care and Outcomes Research Interdisciplinary Working Group; and the American College of Cardiology Foundation In Collaboration With the Heart Rhythm Society.
Strickberger SA, Benson DW, Biaggioni I, Callans DJ, Cohen MI, Ellenbogen KA, Epstein AE, Friedman P, Goldberger J, Heidenreich PA, Klein GJ, Knight BP, Morillo CA, Myerburg RJ, Sila CA, American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, Quality of Care and Outcomes Research Interdisciplinary Working Group, American College of Cardiology Foundation, Heart Rhythm Society
(2006) J Am Coll Cardiol 47: 473-84
MeSH Terms: Adult, Aged, Child, Electrocardiography, Electrophysiologic Techniques, Cardiac, Heart Diseases, Humans, Neurologic Examination, Syncope
Added December 10, 2013
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9 MeSH Terms