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Biomedical subjects

M I Shevell

Publications and source records attributed to M I Shevell.

At least 55 records · Page 3Linked to original sources
PubMed1996

"Pseudo-BECRS": intracranial focal lesions suggestive of a primary partial epilepsy syndrome.

Benign epilepsy of childhood with rolandic spikes (BECRS) is an electroclinical entity that is the most common primary partial epilepsy syndrome of childhood. Typically presenting between the ages of 3 and 13 years, it is characterized by a well-recognized seizure pattern arising in a normal child with EEG findings restricted to rolandic/centrotemporal regions. Seizure control is usually easily achieved and prognosis is believed to be uniformly good. Some authors have suggested that individuals fitting the electroclinical parameters of this entity need not undergo neuroimaging due to the benign evolution of this disorder. Five patients presenting over a 13-year period with peribuccal seizures, normal neurologic examinations, and EEG data initially suggestive of BECRS found to have focal lesions on neuroimaging are summarized. Independent bilateral centrotemporal epileptiform abnormalities were seen in 3 patients. Imaging studies (CT, MRI, or both) documented a mass lesion in all in variable locations. Histologic examination documented a low-grade astrocytoma in 3 patients and a cavernous angioma in another. The fifth patient refused treatment or biopsy. Careful retrospective review of the clinical features of these patients reveals variable atypical features in each. Therefore, despite an electroclinical phenotype initially suggestive of the BECRS presentation, the presence of atypical clinical features raises the possibility of an underlying structural lesion and thus a negative neuroimaging study may in some patients be essential to the definitive accurate diagnosis of BECRS.

Adolescent↗
PubMed1996

Acephalgic migraines of childhood.

Migraine aura without headache (acephalgic migraines) is a recognized subset of migrainous phenomena in the adult population. No reports of its prevalence or characteristics in a series of children exists. Using diagnostic criteria for migraine aura without headache established by the International Headache Society, a retrospective review of a computerized database of all patients referred over a 4-year period (July 1991 to June 1995 inclusive) to a single university-based pediatric neurologist was performed. Fourteen patients were identified, representing 2% of all patients with a primary diagnosis of migraine. Nine were females and 13 had a strong family history of migraines. Age of onset of symptoms ranged from 5 to 12 years with a mean of 8 years. Symptoms were episodic in all, varying in frequency from weekly to more typically monthly, lasting generally less than 10 min. In 9 patients the aura described was that of often colorful photopsias or scintillating scotomas. Two had micropsia, one had temporal distortion (time "speeded up"), one had hyperacusis, and the final patient had a vague sense of disconnection from her surroundings. Only 2 patients had a headache occasionally associated with the described aura. In addition to the acephalgic migraines, 9 patients had either common or classical migraines, the latter typically featuring aura distinct from those observed in these patients' acephalgic episodes. Neurologic examination, electrophysiologic investigation (EEG/evoked potentials), and neuroimaging were noncontributory in all instances. Migraine aura without headache is a recognizable benign migraine syndrome of late childhood.

Child↗
PubMed1996

Clinical features of developmental disability associated with cerebellar hypoplasia.

Sporadic nonsyndromic cerebellar hypoplasia is a radiological diagnosis with clinical features and a relation with developmental disability that are presently not known. Through a retrospective review of a comprehensive standardized computerized database containing more than 2,500 patients examined consecutively by a pediatric neurologist, 11 with nonfamilial, nonsyndromic cerebellar hypoplasia on neuroimaging (CT and/or MRI) were identified. With the exception of two patients, all had been originally referred during infancy or the preschool years for assessment of a developmental disability. All 11 had "cerebellar" findings on initial examination and five were microcephalic; three others were below the 10th percentile. All exhibited developmental disability, commonly of mild to moderate degree. Motor involvement predominated, often involving fine motor skills more than gross motor functions. Imaging consistently disclosed vermis hypoplasia with additional supratentorial cerebral dysgenesis in one child and cerebellar hemispheric hypoplasia in another. Cerebellar hypoplasia is a developmental anomaly that appears to be either etiologically related to, or a marker for, developmental disability, thus confirming the intact cerebellum's integral role in normal psychomotor development. This series suggests that cerebellar hypoplasia should be considered in the young child presenting with developmental delay with prominent motor involvement, together with cerebellar signs and/or microcephaly.

Cerebellar Diseases↗
PubMed1996

Evidence of a third locus for benign familial convulsions.

Two autosomal dominant forms of benign idiopathic epilepsy of early life have been described: benign neonatal familial convulsions and benign infantile familial convulsions. Herein we describe a pedigree with familial convulsions in which the age of onset is intermediate between that seen in these two disorders. Two genes responsible for benign neonatal familial convulsions have been mapped to chromosome 20q and to chromosome 8q. Previously, the chromosome 20q benign neonatal familial convulsions locus had been excluded in this pedigree. Further linkage analysis in our laboratory revealed that the chromosome 8 benign neonatal familial convulsions locus also is not responsible for seizures in this pedigree. These results indicate that there are at least three loci responsible for autosomal dominant benign epilepsies of early life.

Age of Onset↗
PubMed1995

Adenylosuccinate lyase (ADSL) and infantile autism: absence of previously reported point mutation.

Autism is a heterogeneous neuropsychiatric syndrome of unknown etiology. There is evidence that a deficiency in the enzyme adenylosuccinate lyase (ADSL), essential for de novo purine biosynthesis, could be involved in the pathogenesis of certain cases. A point mutation in the ADSL gene, resulting in a predicted serine-to-proline substitution and conferring structural instability to the mutant enzyme, has been reported previously in 3 affected siblings. In order to determine the prevalence of the mutation, we PCR-amplified the exon spanning the site of this mutation from the genomic DNA of patients fulfilling DSM-III-R criteria for autistic disorder. None of the 119 patients tested were found to have this mutation. Furthermore, on preliminary screening using singlestrand conformation polymorphism (SSCP), no novel mutations were detected in the coding sequence of four ADSL exons, spanning approximately 50% of the cDNA. In light of these findings, it appears that mutations in the ADSL gene represent a distinctly uncommon cause of autism.

Adenylosuccinate Lyase↗
PubMed1995

Glutaric acidemia type II: neuroimaging and spectroscopy evidence for developmental encephalomyopathy.

Glutaric acidemia type II is associated with neonatal hypoketotic hypoglycemia, metabolic acidosis, profound hypotonia, progressive cardiomyopathy, and early death. Deficiency of either electron transfer flavoprotein or electron transport flavoprotein:ubiquinone oxidoreductase leads to intramitochondrial accumulation of metabolites of compounds oxidized by enzymes that transfer electrons to flavoprotein. No detailed results of antemortem neuroimaging or magnetic resonance spectroscopy have been described previously. We investigated a patient with typical neonatal onset glutaric acidemia type II without obvious dysmorphogenesis or renal malformations. Cranial tomographic scan revealed hypoplastic temporal lobes and marked widening of the sylvian fissures ("bat-wing" appearance). Cranial magnetic resonance imaging documented underdeveloped frontal and temporal lobes with delayed myelination and hypoplasia of the corpus callosum. 31P-Magnetic resonance spectroscopy of muscle was grossly abnormal with a very low energy state consistent with mitochondrial dysfunction. 1H-Magnetic resonance spectroscopy of brain revealed elevated intracerebral lactate concentration and abnormally high choline/creatine ratio suggestive of dysmyelination. These findings constitute the first in vivo evidence of a developmental encephalomyopathy in glutaric acidemia type II.

Age of Onset↗
PubMed1995

Diagnostic yield of the neurologic assessment of the developmentally delayed child.

OBJECTIVE: The aim of this study was to determine the etiologic yield of the neurologic assessment of a consecutive cohort of developmentally delayed children. STUDY DESIGN: A retrospective chart review was carried out on all patients referred to a single university-based pediatric neurologist for evaluation of global developmental delay from July 1991 to December 1993. Patients referred because of isolated speech or motor delay or autism or those who had been previously evaluated by another neurologist were excluded. RESULTS: A total of 77 patients were identified; 47 were male, and 62 were referred by a pediatrician. Neurologic evaluation did not confirm global delay in 10, and 8 did not complete diagnostic evaluation; one child was included in both groups. Of the remaining 60, an etiologic diagnosis was suspected by the referring physician at the time of referral in 13. Although parents suspected a delay at a mean age of 0.66 (+/- 0.69) year, children were examined by the neurologist at a mean age of 3.58 (+/- 2.42) years. Twenty-five were mildly delayed, 23 were moderately delayed, and 12 were severely delayed. Diagnostic studies (history, physical examination, and selected investigations, including screens for metabolic disease, karyotype, fragile X testing, electroencephalography, and neuroimaging) yielded an etiologic diagnosis in 38 (63.3%) of the 60 patients. Etiologic categories included cerebral dysgenesis (16.7%), hypoxic-ischemic encephalopathy (10.0%), chromosomal abnormalities (10%), toxins (8.3%), metabolic disorders (5.0%), and neurocutaneous (3.3%), neuromuscular (3.3%), genetic/dysmorphic (3.3%), and epileptic (3.3%) syndromes. Etiologic yield was equivalent across categories and degree of developmental delay. CONCLUSION: Referral to a pediatric neurologist and application of a selected battery of investigations yield etiologic findings with important implications with respect to management, prognosis, and recurrence risk estimate in a significant portion of globally delayed children.

Child, Preschool↗
PubMed1995

Right-hemisphere dysfunction in Asperger's syndrome.

Asperger's syndrome has many clinical features in common with acquired right-hemisphere dysfunction and has been postulated to result from a developmental abnormality of the right hemisphere. However, right-hemisphere abnormality has not previously been documented on neuroanatomic or functional imaging in patients with Asperger's syndrome. We report three patients with Asperger's syndrome found to have abnormal right-hemisphere function on single photon emission computed tomographic (SPECT) imaging. The subjects were two males and one female, ranging from 12 to 16 years of age. All were diagnosed on the basis of the presence of the complete constellation of clinical features previously outlined. All patients were investigated with computed tomographic (CT) scanning, magnetic resonance imaging (MRI), and SPECT scanning. In one subject, CT and MRI revealed enlargement of the right lateral ventricle, reflecting a mild degree of right hemispheric atrophy. CT and MRI studies on the other two subjects were normal. SPECT scanning demonstrated right hemispheric abnormalities in each subject: right temporal hypoperfusion with a central area of increased perfusion along with frontal polar hyperperfusion in one; diffusely decreased right hemispheric uptake in the second; and decreased frontal and occipital uptake in the third. Cerebellar abnormalities were also present: a smaller right hemisphere with increased uptake in the first; decreased uptake in the vermis and right hemisphere in the second; and decreased vermal uptake in the third. These findings support the hypothesis that the neurobiologic basis of Asperger's syndrome is a developmental abnormality of the right cerebral hemisphere.

Adolescent↗
PubMed1994

Encephaloduroarteriosynangiosis (EDAS) for the treatment of childhood moyamoya disease.

Moyamoya disease is defined by the angiographic demonstration of stenosis or occlusion of the vessels of the anterior circulation at the base of the brain and the concomitant development of collateral blood supply. Untreated, the disease is often clinically progressive, resulting in significant neurologic sequelae. Encephaloduroarteriosynangiosis (EDAS), which involves the transposition of a segment of a scalp artery onto the surface of the brain, is a surgical treatment aimed at improving collateral blood flow. Six children underwent 8 EDAS procedures and were followed from 6 months to 9 years after surgery. No patient experienced further deterioration in neurologic status. Postoperative angiography demonstrated cerebral revascularization from the donor scalp artery on 3 of the 6 EDASs that were studied. The 2 patients who did not revascularize after EDAS demonstrated angiographic regression of their disease. The data suggest that EDAS is a safe procedure for the treatment of childhood moyamoya disease. Given the potential severity of the sequelae, early operative intervention is recommended in all children with this disease.

Anastomosis, Surgical↗
PubMed1994

Magnetic resonance spectroscopy in Niemann-Pick disease type C: correlation with diagnosis and clinical response to cholestyramine and lovastatin.

Niemann-Pick type C is an autosomal-recessive, neurovisceral storage disorder that results from defective cholesterol esterification. Cholesterol-lowering agents have been demonstrated to decrease hepatic lipids in Niemann-Pick type C patients. The objective was to determine the effects of cholesterol-lowering agents on neurologic features and to develop a noninvasive method of monitoring clinical response. A 9-month-old boy with progressive hepatosplenomegaly and neurodevelopmental delay was studied. Water-suppressed proton magnetic resonance spectra from a supraventricular volume of central white and gray matter revealed an abnormal lipid signal. The patient was treated with cholesterol-lowering agents (i.e., cholestyramine, lovastatin). Repeat standardized neurodevelopmental assessments (Peabody and Griffith scales) at 13 and 19 months were normal and magnetic resonance spectra no longer detected the previously observed lipid resonance. Early treatment of Niemann-Pick type C patients with cholesterol-lowering agents appeared to have short-term beneficial effects. Magnetic resonance spectra provided a noninvasive means of monitoring CNS response.

Brain↗
PubMed1994

Cerebral dysgenesis and lactic acidemia: an MRI/MRS phenotype associated with pyruvate dehydrogenase deficiency.

Pyruvate dehydrogenase complex (PDHC) is an intramitochondrial multienzyme complex essential for the aerobic oxidation of glucose. The majority of patients with PDHC deficiency have abnormalities in the major catalytic and regulatory subunit, E1 alpha, which is encoded on the X chromosome. The clinical spectrum of PDHC deficiency is heterogeneous, particularly in heterozygous females, and diagnosis may be difficult. Three affected infant girls with PDHC deficiency were investigated. All had dysmorphic features, microcephaly with profound global developmental delay, and hypotonia. Systemic acidosis was absent, although serum lactate and pyruvate were abnormally elevated. Magnetic resonance imaging revealed hypoplasia of the corpus callosum in all patients. Proton magnetic resonance spectroscopy of brain revealed large increases in relative signal intensities for lactic acid and decreases in the relative signal intensities of N-acetylaspartate, a marker of neuronal damage or less. Phosphorus MRS of muscle revealed abnormally low phosphorylation potentials for all these patients, although the degree of abnormality was variable and not directly correlated with the amount of brain lactate. It is proposed that cerebral dysgenesis and cerebral lactic acidemia as shown by magnetic resonance imaging and proton magnetic resonance spectroscopy are useful diagnostic clues to PDHC deficiency, particularly in females in whom variable patterns of X-inactivation reduce sensitivity of laboratory diagnosis based on the biochemical studies of peripheral tissues. In addition, muscle bioenergetic abnormalities in conjunction with CNS dysfunction may contribute to profound hypotonia in this disorder.

Acidosis, Lactic↗
PubMed1993

Varying neurological phenotypes among muto and mut- patients with methylmalonylCoA mutase deficiency.

MethylmalonylCoA mutase (MCM) is a mitochondrial homodimer responsible for the isomerization of methylmalonylCoA to succinylCoA. Apomutase defects are traditionally divided into muto and mut- classes on the basis of residual mutase activity. Clinical findings were reviewed in 20 patients with methylmalonic aciduria secondary to MCM deficiency. All 11 muto patients had an early neonatal presentation; 6 of these patients died in infancy and 3 of 5 survivors had a poor neurological outcome as evidenced by severe delay or spastic quadriparesis with dystonia. The 2 other survivors include a 27-month-old child with a mild delay in verbal and fine motor skills and an adolescent with low normal intelligence. Of the 9 mut- patients, 7 became symptomatic in late infancy or childhood and 2 were picked up on screening. Two of the 9 patients have never had an episode of metabolic decompensation yet both are neurologically compromised; one severely retarded and autistic, the other mildly delayed. Four mut- patients have had episodic acidosis and are neurologically moderately affected, while 3 have had episodic acidosis and are neurologically intact. These results confirm phenotypic pleomorphism without a consistent pattern of neurological injury and suggest some broad correlation between mutase class and phenotype. Survival with good outcome is possible among muto patients as is significant morbidity among mut- patients. Acidosis and metabolic imbalance are not necessary preconditions for significant morbidity.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

Searching for human epilepsy genes: a progress report.

Application of new genetic techniques has brought remarkable discoveries in the study of genetic diseases. The potential benefits from applying such technology to idiopathic epilepsies include improved understanding of cellular mechanisms and potential new methods of prevention and treatment. The complex problems involved in studying the hereditary epilepsies include: defining of specific phenotypes; detecting genetic and non-genetic heterogeneity; and specifying the appropriate mode of inheritance and penetrance. The gene loci for three primary epilepsies have been localized to specific chromosomal regions, and serve to demonstrate the process used in generalized linkage studies of hereditary epilepsy syndromes. Benign familial neonatal convulsions (BFNC) and Unverricht-Lundborg progressive myoclonus epilepsy are rare single-gene disorders that are sufficiently localized to chromosomal regions that positional cloning studies are likely to succeed. Juvenile myoclonic epilepsy (JME), a common hereditary syndrome with an uncertain mode of inheritance, has been reported to be linked to chromosome 6p. JME presents a challenge for generalized linkage methodology that may be overcome by attending to potential problems reviewed here. The candidate-gene method, combined with studies using animal models, holds promise for understanding these as well as other hereditary epilepsies.

Animals↗
PubMed1993

Inflammatory myopathy and Walker-Warburg syndrome: etiologic implications.

Walker-Warburg syndrome is a well delineated clinical entity with characteristic brain and eye anomalies. Recent diagnostic surveys have revealed that muscular dystrophy is an obligatory feature of this syndrome. We report a patient with an inflammatory myopathy that preceded dystrophic changes. While reports of parental consanguinity and multiple affected sibships strongly suggest an autosomal recessive genetic basis for this syndrome, previous pathological analyses of the CNS have suggested an inflammatory process. Our case supports both the notion of an aberrant inflammatory process that is likely under genetic control or etiologic heterogeneity (phenocopies) underlying this syndrome.

Brain↗
PubMed1992

A comparison of neurobehavioral performance of healthy term and low-risk preterm infants at term.

The neurobehavioral performance of a group of low-risk preterm and healthy term infants was assessed at term using the standardized Einstein Neonatal Neurobehavioral Assessment Scale. There was greater similarity than dissimilarity between the two groups; however, preterm infants demonstrated less consistent following to face and voice, and less sustained rooting and grasp reflexes. Preterm infants were more likely to have a more sustained asymmetric tonic neck reflex, a greater popliteal angle and evidence of tremor. These results support the view that processing capability appears to mature on an intrinsically programmed time- and environment-independent pathway, with environmental exposure challenging this adaptive capacity and modifying performance--predominantly with respect to reflexive elements.

Arousal↗