Publications by authors named "Dean Sarco"

17 Publications

  • Page 1 of 1

Encephalopathies with KCNC1 variants: genotype-phenotype-functional correlations.

Ann Clin Transl Neurol 2019 07 1;6(7):1263-1272. Epub 2019 Jul 1.

Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Melbourne, Australia.

Objective: To analyze clinical phenotypes associated with KCNC1 variants other than the Progressive Myoclonus Epilepsy-causing variant p.Arg320His, determine the electrophysiological functional impact of identified variants and explore genotype-phenotype-physiological correlations.

Methods: Ten cases with putative pathogenic variants in KCNC1 were studied. Variants had been identified via whole-exome sequencing or gene panel testing. Clinical phenotypic data were analyzed. To determine functional impact of variants detected in the K 3.1 channel encoded by KCNC1, Xenopus laevis oocyte expression system and automated two-electrode voltage clamping were used.

Results: Six unrelated patients had a Developmental and Epileptic Encephalopathy and a recurrent de novo variant p.Ala421Val (c.1262C > T). Functional analysis of p.Ala421Val revealed loss of function through a significant reduction in whole-cell current, but no dominant-negative effect. Three patients had a contrasting phenotype of Developmental Encephalopathy without seizures and different KCNC1 variants, all of which caused loss of function with reduced whole-cell currents. Evaluation of the variant p.Ala513Val (c.1538C > T) in the tenth case, suggested it was a variant of uncertain significance.

Interpretation: These are the first reported cases of Developmental and Epileptic Encephalopathy due to KCNC1 mutation. The spectrum of phenotypes associated with KCNC1 is now broadened to include not only a Progressive Myoclonus Epilepsy, but an infantile onset Developmental and Epileptic Encephalopathy, as well as Developmental Encephalopathy without seizures. Loss of function is a key feature, but definitive electrophysiological separation of these phenotypes has not yet emerged.
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http://dx.doi.org/10.1002/acn3.50822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649578PMC
July 2019

encephalopathy: A new disease of vesicle fission.

Neurology 2017 Jul 30;89(4):385-394. Epub 2017 Jun 30.

Author affiliations are provided at the end of the article.

Objective: To evaluate the phenotypic spectrum caused by mutations in dynamin 1 (), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling.

Methods: We reviewed phenotypic data of 21 patients (7 previously published) with mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function.

Results: We identified 19 patients with de novo mutations in and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function.

Conclusions: The phenotypic spectrum of -related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention.
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http://dx.doi.org/10.1212/WNL.0000000000004152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574673PMC
July 2017

Copy number variation plays an important role in clinical epilepsy.

Ann Neurol 2014 Jun 13;75(6):943-58. Epub 2014 Jun 13.

Epilepsy Genetics Program, Division of Epilepsy and Clinical Neurophysiology and Neurogenetics Program, Department of Neurology, Boston Children's Hospital, and Harvard Medical School, Boston, MA.

Objective: To evaluate the role of copy number abnormalities detectable using chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center.

Methods: We identified patients with International Classification of Diseases, ninth revision (ICD-9) codes for epilepsy or seizures and clinical CMA testing performed between October 2006 and February 2011 at Boston Children's Hospital. We reviewed medical records and included patients who met criteria for epilepsy. We phenotypically characterized patients with epilepsy-associated abnormalities on CMA.

Results: Of 973 patients who had CMA and ICD-9 codes for epilepsy or seizures, 805 patients satisfied criteria for epilepsy. We observed 437 copy number variants (CNVs) in 323 patients (1-4 per patient), including 185 (42%) deletions and 252 (58%) duplications. Forty (9%) were confirmed de novo, 186 (43%) were inherited, and parental data were unavailable for 211 (48%). Excluding full chromosome trisomies, CNV size ranged from 18kb to 142Mb, and 34% were >500kb. In at least 40 cases (5%), the epilepsy phenotype was explained by a CNV, including 29 patients with epilepsy-associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or "hotspots." We observed numerous recurrent CNVs including 10 involving loss or gain of Xp22.31, a region described in patients with and without epilepsy.

Interpretation: Copy number abnormalities play an important role in patients with epilepsy. Because the diagnostic yield of CMA for epilepsy patients is similar to the yield in autism spectrum disorders and in prenatal diagnosis, for which published guidelines recommend testing with CMA, we recommend the implementation of CMA in the evaluation of unexplained epilepsy.
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http://dx.doi.org/10.1002/ana.24178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487364PMC
June 2014

Sturge-Weber syndrome: clinical and radiological correlates in 86 patients.

Ideggyogy Sz 2013 Jan;66(1-2):53-7

Epilepsy Center, Bethesda Children's Hospital, Budapest, Hungary.

Backgrounds And Purpose: To correlate the extent of the leptomeningeal angiomatosis with clinical features in Sturge-Weber syndrome (SWS).

Methods: The study group consisted of 86 consecutive patients aged two months to 56 (mean 7.9 +/- 10.3) years with SWS and epilepsy. Clinical and MRI data were analyzed.

Results: Based on the extent of leptomeningeal angiomatosis, patients were divided into two subgroups: 43 patients had hemispheric angiomatosis and atrophy, whereas, another 43 had focal involvement. Nine of the 43 hemispherial patients (10%) showed bilateral involvement: all of these bilateral cases demonstrated dominance in a single side with hemispheric leptomeningeal angiomatosis and contralateral focal extension. Hemispheric and focal subgroups were clinically different. Patients with hemispheric SWS were younger at the age of epilepsy onset (p < 0.001) and age at MRI examination (p < 0.05). Neither gender, lateralization, duration of epilepsy, appearance of secondarily generalized seizures, nor seizure frequency revealed a significant difference between subgroups.

Conclusion: Bilateral involvement is frequent and occurs in cases with a hemisperic involvement on one side. The age of epilepsy onset is related to the extent of leptomeningeal angiomatosis. Patients with hemispheric form of SWS presented with earlier age of seizure onset. Focal pial angiomatoses do not tend to progress (a longer duration is not associated with more frequent hemispheric involvement). Other variables including seizure frequency and secondary generalized tonic-clonic seizures are not associated with the extent of angiomatosis.
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January 2013

Yield of emergent neuroimaging among children presenting with a first complex febrile seizure.

Pediatr Emerg Care 2012 Apr;28(4):316-21

Divisions of Emergency Medicine, Children's Hospital Boston, Boston, MA 02115, USA.

Objectives: The objective of this study was to assess the risk of intracranial pathology requiring immediate intervention among children presenting with their first complex febrile seizure (CFS).

Design/methods: This is a retrospective cohort review of patients 6 to 60 months of age evaluated in a pediatric emergency department between 1995 and 2008 for their first CFS. Cases were identified using computerized text search followed by manual chart review. We excluded patients with a prior history of a nonfebrile seizure disorder or a prior CFS, an immune-compromised state, an underlying illness associated with seizures or altered mental status, or trauma. Data extraction included age, sex, seizure features, prior simple febrile seizures, temperature, family history of seizures, vaccination status, findings on physical examination, laboratory and imaging studies, diagnosis, and disposition.

Results: We identified a first CFS in 526 patients. Two hundred sixty-eight patients (50.4%) had emergent head imaging: 4 patients had a clinically significant finding: 2 had intracranial hemorrhage, 1 had acute disseminated encephalomyelitis, and 1 patient had focal cerebral edema (1.5%; 95% confidence interval, 0.5%-4.0%). Assigning low risk to patients not imaged and not returning to the emergency department within a week of the original visit, the risk of intracranial pathology in our sample was 4 (0.8%; 95% confidence interval, 0.2%-2.1%) of 526. Three of these 4 patients had other obvious findings (nystagmus, emesis, and altered mental status; persistent hemiparesis; bruises suggestive of inflicted injury).

Conclusions: Very few patients with CFSs have intracranial pathology in the absence of other signs or symptoms. Patients presenting with more than one seizure in 24 hours in particular are at very low risk.
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http://dx.doi.org/10.1097/PEC.0b013e31824d8b0bDOI Listing
April 2012

Analysis of EEG patterns and genotypes in patients with Angelman syndrome.

Epilepsy Behav 2012 Mar 16;23(3):261-5. Epub 2012 Feb 16.

Boston University, Neurology Department, C-3, Boston, MA 02118, USA.

We prospectively analyzed EEGs from participants in the ongoing NIH Rare Diseases Clinical Research Network Angelman Syndrome Natural History Study. Of the one-hundred-sixty enrolled patients (2006-2010), 115 had complete data (58 boys, median age 3.6 years). Distinct EEG findings were intermittent rhythmic delta waves (83.5%), interictal epileptiform discharges (74.2%), intermittent rhythmic theta waves (43.5%), and posterior rhythm slowing (43.5%). Centro-occipital and centro-temporal delta waves decreased with age (p=0.01, p=0.03). There were no specific correlations between EEG patterns and genotypes. A classification tree allowed the prediction of deletions class-1 (5.9 Mb) in patients with intermittent theta waves in <50% of EEG and interictal epileptiform abnormalities; UPD, UBE3A mutation or imprinting defects in patients with intermittent theta in <50% of EEG without interictal epileptiform abnormalities; deletions class-2 (5.0 Mb) in patients with >50% theta and normal posterior rhythm; atypical deletions in patients with >50% theta but abnormal posterior rhythm. EEG patterns are important biomarkers in Angelman syndrome and may suggest the underlying genetic etiology.
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http://dx.doi.org/10.1016/j.yebeh.2011.11.027DOI Listing
March 2012

A therapeutic trial of pro-methylation dietary supplements in Angelman syndrome.

Am J Med Genet A 2011 Dec 14;155A(12):2956-63. Epub 2011 Oct 14.

NIH Rare Diseases Clinical Research Network-Angelman, Rett, & Prader-Willi Syndromes Consortium, USA.

Angelman syndrome (AS) is due to deficient ubiquitin protein ligase 3a, the gene for which (UBE3A) maps to chromosome 15q11-q13 and is imprinted such that only the maternally inherited gene is expressed. The paternally inherited UBE3A gene is silenced, a process mediated by an antisense transcript. We conducted a trial using methylation-promoting dietary supplements (betaine, metafolin, creatine, and vitamin B(12) ) in an attempt to reduce antisense transcript production, increase UBE3A expression, and ameliorate the symptoms of AS. Neuropsychological evaluations, biochemical testing, and assessment of DNA methylation were performed at the beginning and at the end of 1 year of supplementation. The primary outcome measures were changes in the level of developmental function (cognitive, motor, and language) as measured using standardized instruments. The secondary outcomes measures were changes in biochemical parameters and global DNA methylation. These data were compared to those of a control group from a previous randomized double-blind trial using folic acid and betaine. There were no statistically significant changes in the developmental performance of children treated with supplements. There were no unexpected changes in biochemical parameters and no change in site-specific DNA methylation when comparing samples from before and after treatment. There were 10 adverse events that resulted in study withdrawal of 7 participants (worsening of seizures, onset, or worsening of sleep problems, constipation, and anorexia). Supplementation with betaine, metafolin, creatine, and vitamin B(12) appears safe but ineffective in decreasing the severity of AS.
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http://dx.doi.org/10.1002/ajmg.a.34297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222728PMC
December 2011

Benign rolandic epileptiform discharges are associated with mood and behavior problems.

Epilepsy Behav 2011 Oct 20;22(2):298-303. Epub 2011 Aug 20.

Department of Neurology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA.

Children with benign rolandic epilepsy (BRE) experience elevated rates of cognitive, behavioral, and affective problems. Frequent epileptiform spike discharges may impair behavioral functioning. To elucidate this relationship, we evaluated associations between the EEG spike frequency index (SI) and parental ratings of psychosocial adjustment and executive functioning in school-aged children with EEGs typical of BRE. Twenty-one children (6-12 years) participated. Parents completed validated questionnaires at a median of 5 months (range: 1-8) after a routine outpatient EEG. The EEG SI was calculated for wakefulness and sleep. The strength of association between the SI and behavioral variables was evaluated by simple and multivariate correlation. Higher awake and sleep SIs were associated with more symptoms of depression (P<0.001), aggression and conduct problems (P<0.01). Higher sleep SI was associated with executive dysfunction and anxiety (P<0.05). Symptoms of hyperactivity and inattention had no correlation. Increased epileptiform activity in children with BRE may predict higher rates of mood and behavioral problems.
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http://dx.doi.org/10.1016/j.yebeh.2011.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030107PMC
October 2011

Angelman syndrome: Mutations influence features in early childhood.

Am J Med Genet A 2011 Jan;155A(1):81-90

Children's Hospital Boston, Harvard Medical School, Massachusetts, USA.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by a lack of expression of the maternal copy of UBE3A. Although the "classic" features of AS are well described, few large-scale studies have delineated the clinical features in AS. We present baseline data from 92 children with a molecular diagnosis of AS between 5 and 60 months old who are enrolled in the National Institutes of Health Rare Diseases Clinical Research Network Angelman Syndrome Natural History Study from January 2006 to March 2008. Seventy-four percent of participants had deletions, 14% had either uniparental disomy (UPD) or imprinting defects, and 12% had UBE3A mutations. Participants with UPD/imprinting defects were heavier (P = 0.0002), while those with deletions were lighter, than the general population (P < 0.0001). Twenty out of 92 participants were underweight, all of whom had deletions or UBE3A mutations. Eight out of 92 participants (6/13 (46%) with UPD/imprinting defects and 2/11 (18%) with UBE3A mutations) were obese. Seventy-four out of 92 participants (80%) had absolute or relative microcephaly. No participant was macrocephalic. The most common behavioral findings were mouthing behavior (95%), short attention span (92%), ataxic or broad-based gait (88%), history of sleep difficulties (80%), and fascination with water (75%). Frequent, easily provoked laughter was observed in 60%. Clinical seizures were reported in 65% of participants but all electroencephalograms (EEGs) were abnormal. We conclude that the most characteristic feature of AS is the neurobehavioral phenotype, but specific EEG findings are highly sensitive for AS. Obesity is common among those with UPD/imprinting defects.
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http://dx.doi.org/10.1002/ajmg.a.33775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563320PMC
January 2011

Yield of lumbar puncture among children who present with their first complex febrile seizure.

Pediatrics 2010 Jul 21;126(1):62-9. Epub 2010 Jun 21.

Division of Emergency Medicine, Department of Medicine, Children's Hospital Boston, Boston, MA 02115, USA.

Objective: To assess the rate of acute bacterial meningitis (ABM) among children who present with their first complex febrile seizure (CFS).

Design And Methods: This study was a retrospective, cohort review of patients aged 6 to 60 months who were evaluated in a pediatric emergency department (ED) between 1995 and 2008 for their first CFS. Cases were identified by using a computerized text search followed by a manual chart review. Exclusion criteria included prior history of nonfebrile seizures, an immunocompromised state, an underlying illness associated with seizures or altered mental status, or trauma. Data extracted included age, gender, seizure features, the number of previous simple febrile seizures, temperature, a family history of seizures, findings on physical examination, laboratory and imaging study results, and ED diagnosis and disposition.

Results: We identified 526 patients. The median age was 17 months (interquartile range: 13-24), and 44% were female. Ninety patients (17%) had a previous history of simple febrile seizures. Of the patients, 340 (64%) had a lumbar puncture (LP). The patients' median white blood cell count during a CFS was 1 cell per microL (interquartile range: 1-2), and 14 patients had CSF pleocytosis (2.7% [95% confidence interval [CI]: 1.5-4.5]). Three patients had ABM (0.9% [95% CI: 0.2-2.8]). Two had Streptococcus pneumoniae in a culture of their cerebrospinal fluid. Among these 2 patients, 1 was nonresponsive during presentation, and the other had a bulging fontanel and apnea. The third child appeared well; however, her blood culture grew S pneumoniae and failed the LP test. None of the patients for whom an LP was not attempted subsequently returned to the hospital with a diagnosis of ABM (0% [95% CI: 0, 0.9]).

Conclusion: Few patients who experienced a CFS had ABM in the absence of other signs or symptoms.
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http://dx.doi.org/10.1542/peds.2009-2741DOI Listing
July 2010

Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders.

Am J Med Genet B Neuropsychiatr Genet 2010 Jun;153B(4):937-47

Division of Developmental Medicine, Children's Hospital Boston, Boston, Massachusetts 02115, USA.

Research has implicated mutations in the gene for neurexin-1 (NRXN1) in a variety of conditions including autism, schizophrenia, and nicotine dependence. To our knowledge, there have been no published reports describing the breadth of the phenotype associated with mutations in NRXN1. We present a medical record review of subjects with deletions involving exonic sequences of NRXN1. We ascertained cases from 3,540 individuals referred clinically for comparative genomic hybridization testing from March 2007 to January 2009. Twelve subjects were identified with exonic deletions. The phenotype of individuals with NRXN1 deletion is variable and includes autism spectrum disorders, mental retardation, language delays, and hypotonia. There was a statistically significant increase in NRXN1 deletion in our clinical sample compared to control populations described in the literature (P = 8.9 x 10(-7)). Three additional subjects with NRXN1 deletions and autism were identified through the Homozygosity Mapping Collaborative for Autism, and this deletion segregated with the phenotype. Our study indicates that deletions of NRXN1 predispose to a wide spectrum of developmental disorders.
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http://dx.doi.org/10.1002/ajmg.b.31063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001124PMC
June 2010

The safety and tolerability of newer antiepileptic drugs in children and adolescents.

CNS Drugs 2010 May;24(5):399-430

Department of Neurology, Division of Epilepsy and Clinical Neurophysiology, Children's Hospital Boston, Boston, Massachusetts, USA.

The newer antiepileptic drugs (AEDs) provide more therapeutic options and overall improved safety and tolerability for patients. To provide the best care, physicians must be familiar with the latest tolerability and safety data. This is particularly true in children, given there are relatively fewer studies examining the effects of AEDs in children compared with adults. Since we now have significant paediatric literature on each of these agents, we provide a comprehensive and current literature review of the newer AEDs, focusing on safety and tolerability data in children and adolescents. Because the safety profiles in children differ from those in adults, familiarity with this literature is important for child neurologists and other paediatric caregivers. We have organized the data by organ system for each AED for easier reference.
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http://dx.doi.org/10.2165/11310980-000000000-00000DOI Listing
May 2010

Septo-optic dysplasia complicated by infantile spasms and bilateral choroidal fissure arachnoid cysts.

J Neuroimaging 2011 Jan;21(1):89-91

Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Children's Hospital Boston, Boston, MA 02115, USA.

Background And Purpose: septo-optic dysplasia (SOD) is the triad of optic nerve hypoplasia, panhypopituitarism, and agenesis of septum pellucidum, and has been described previously to be associated with heterotopias and midline interhemispheric cyst. We describe a case of SOD with arachnoid cysts, persistent primary hyperplastic vitreous, and malformations of cortical development.

Methods: case report and review of literature.

Results: our patient was found to have SOD, bilateral ventriculomegaly, pachygyria, gray matter heterotopia, bilateral choroidal cysts near the brainstem, and persistent primary hyperplastic vitreous. She later developed infantile spasms and required enucleation of the abnormal eye and cyst fenestration.

Conclusion: coincidence of seizures, SOD, bilateral choroid fissure cysts, heterotopias, and persistent primary hyperplastic vitreous is a unique constellation. It is unclear whether this represents a new syndrome or SOD spectrum variation. Patients with SOD and arachnoid cysts should be monitored for signs of herniation.
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http://dx.doi.org/10.1111/j.1552-6569.2009.00453.xDOI Listing
January 2011

Oxcarbazepine in children with nocturnal frontal-lobe epilepsy.

Pediatr Neurol 2007 Nov;37(5):345-9

Department of Neurology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.

Nocturnal frontal-lobe epilepsy is characterized by paroxysmal arousals, motor seizures with dystonic or hyperkinetic features, and episodic nocturnal wanderings. Carbamazepine is effective for seizure control in some of these patients, but seizures may be refractory to multiple antiepileptic drugs. We report on eight children between ages 4-16 years with nocturnal frontal-lobe epilepsy who had a dramatic response to oxcarbazepine at standard recommended doses, some of whom were refractory to previous antiepileptic medications. Brain magnetic resonance imaging, routine electroencephalogram, and prolonged, continuous video-electroencephalogram telemetry were performed in all children. Nocturnal frontal-lobe epilepsy was diagnosed by demonstrating ictal electroencephalogram changes originating from the frontal lobes. The children were followed for response of seizures to oxcarbazepine, side effects, and routine blood tests, including serum 10-monohydroxide derivative levels. The mean oxcarbazepine dose was 30.4 mg/kg/day +/- 11.7 (mean +/- SD); the mean 10-monohydroxide level was 23.1 microg/mL +/- 8.6 (mean +/- SD). Seizures improved within 4 days of oxcarbazepine initiation in six children, whereas two children required higher doses. Their follow-up has ranged from 12 to 24 months, without seizure recurrence or serious side effects. Our patients demonstrate the efficacy of oxcarbazepine for nocturnal hyperkinetic seizures in children with nocturnal frontal-lobe epilepsy.
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http://dx.doi.org/10.1016/j.pediatrneurol.2007.06.013DOI Listing
November 2007

Electroencephalography in epilepsy surgery planning.

Childs Nerv Syst 2006 Aug 13;22(8):760-5. Epub 2006 Jun 13.

Department of Neurology, Division of Epilepsy and Clinical Neurophysiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA, 02115, USA.

Objective: To describe localizing value of surface EEG recording in the presurgical evaluation of medically intractable pediatric epilepsy patients.

Methods: We review the relevant concepts required for understanding the role of surface EEG in the presurgical evaluation and in identifying the epileptogenic zone. The unique features of EEG and its limitations are discussed.

Conclusion: Despite recent technological advancements, surface EEG continues to play a crucial role in defining the epileptogenic zone, and thus in presurgical planning.
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http://dx.doi.org/10.1007/s00381-006-0128-1DOI Listing
August 2006

AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders.

Ann Neurol 2006 Mar;59(3):527-34

Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza, Mendel Institute, Rome, Italy.

Objective: Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. It is characterized by hypoplasia of the cerebellar vermis and a particular midbrain-hindbrain "molar tooth" sign, a finding shared by a group of Joubert syndrome-related disorders (JSRDs), with wide phenotypic variability. The frequency of mutations in the first positionally cloned gene, AHI1, is unknown.

Methods: We searched for mutations in the AHI1 gene among a cohort of 137 families with JSRD and radiographically proven molar tooth sign.

Results: We identified 15 deleterious mutations in 10 families with pure JS or JS plus retinal and/or additional central nervous system abnormalities. Mutations among families with JSRD including kidney or liver involvement were not detected. Transheterozygous mutations were identified in the majority of those without history of consanguinity. Most mutations were truncating or splicing errors, with only one missense mutation in the highly conserved WD40 repeat domain that led to disease of similar severity.

Interpretation: AHI1 mutations are a frequent cause of disease in patients with specific forms of JSRD.
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http://dx.doi.org/10.1002/ana.20749DOI Listing
March 2006

Ataxia and shaking in a 2-year-old girl: acute marijuana intoxication presenting as seizure.

Pediatr Emerg Care 2005 Aug;21(8):527-8

Division of Pediatric Neurology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT 84158, USA.

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http://dx.doi.org/10.1097/01.pec.0000173349.38024.33DOI Listing
August 2005