Biomedical subjects

Charles M Zaroff

Publications and source records attributed to Charles M Zaroff.

8 recordsLinked to original sources

PubMed2006

Mental retardation and relation to seizure and tuber burden in tuberous sclerosis complex.

In patients with tuberous sclerosis complex (TSC), the high rates of mental retardation are associated with cortical tubers, seizure activity, and genetic factors. The goal of the study was to investigate the relationship between bilateral cortical tubers and seizure variables and mental retardation in individuals with TSC. The records of 27 patients with TSC (age 6 months to 33 years) undergoing neuropsychological assessment and the following clinical variables were examined: bilateral versus non-bilateral cortical tubers, the age of seizure onset, and presence of infantile spasms. Results were statistically analyzed. Bilateral cortical tubers (p=0.02) and early age of seizure onset (p=0.04) were significantly related to impaired cognitive functioning. Only one of the seven patients with normal cognitive functioning had bilateral tubers, whereas 13/21 patients with intellectual impairment had bilateral tubers. Patients with normal cognitive functioning experienced a mean age of seizure onset after 6 years. A trend was observed between infantile spasms and cognitive functioning (p=0.06); the lack of statistical significance likely reflects the small sample size. Neither age nor gender was related to cognitive status. Further investigation incorporating additional neuroimaging factors, antiepileptic treatment effects, and genetic variables, is needed.

Adolescent↗

PubMed2006

Epilepsy surgery in young children with tuberous sclerosis: results of a novel approach.

OBJECTIVE: Tuberous sclerosis complex (TSC) is associated with medically refractory epilepsy and developmental delay in children and usually results from cortical tubers. Seizures that begin in young patients are often refractory and may contribute to development delay. Functional outcome is improved when seizures are controlled at an early age. Previous reports have shown modest benefit from surgical resection of single tubers/seizure foci in older children; however, many children with TSC develop uncontrolled seizures before age 1. To identify patients who might benefit from surgery and to maximize outcome, we used a novel surgical approach in young children that consists of invasive intracranial monitoring, which is typically 3-staged and often bilateral. METHODS: Of 110 consecutive children who underwent epilepsy surgery by a single surgeon in the past 6 years, 25 patients (9 boys and 16 girls) had TSC. At the time of their first surgery at our institution, they were a median age of 4.0 years. A total of 31 separate admissions for epilepsy surgery in these 25 patients were identified. Bilateral electrode placement was performed in 13 children whose seizures could not be lateralized definitively preoperatively, and 22 patients underwent 3-stage surgeries. RESULTS: At 6 months or longer after the initial resection, 21 (84%) children were class I, 2 (8%) children were class II, and 2 (8%) children were class IV. At a mean follow-up of 28 months, 17 (68%) children were class I, 6 (24%) were class II, and 2 (8%) were class III. Four of the 5 children who initially were rejected as surgical candidates because of multifocality and who required initial bilateral electrode study are now seizure-free. CONCLUSIONS: This approach can help to identify both primary and secondary epileptogenic zones in young TSC patients with multiple tubers. Multiple or bilateral seizure foci are not necessarily a contraindication to surgery. Long-term follow-up will determine whether this approach has durable effects.

Adolescent↗

PubMed2005

Neurocutaneous syndromes: behavioral features.

Neurocutaneous syndromes are disorders characterized by a neurological abnormality and cutaneous manifestations. Three of the more common neurocutaneous syndromes are Sturge-Weber syndrome, tuberous sclerosis, and neurofibromatosis. This review focuses on the cognitive and behavioral features of these syndromes.

Behavior↗

PubMed2005

Late-onset Tay-Sachs disease: phenotypic characterization and genotypic correlations in 21 affected patients.

PURPOSE: The purpose of this study was to describe the phenotype (and corresponding genotype) of adult patients with late-onset Tay-Sachs disease, a clinical variant of the GM2-gangliosidoses. METHODS: A comprehensive physical examination, including neurological assessments, was performed to establish the current disease pattern and severity. In addition, the patients' past medical histories were reviewed. The patients' alpha-subunit mutations (beta-Hexosaminidase A genotype) were determined and correlated with their corresponding clinical findings and disease course. RESULTS: Twenty-one patients (current mean age: 27.0 years; range: 14-47 years) were identified. The pedigree revealed a relative with the "classic" infantile or late-onset form of Tay-Sachs disease in four (out of 18) unrelated families. The patients were predominantly male (15/21 individuals) and of Ashkenazi Jewish ancestry (15/18 families). Mean age at onset was 18.1 years; balance problems and difficulty climbing stairs were the most frequent presenting complaints. In several cases, the diagnosis was delayed (mean age at diagnosis: 27.0 years). Analysis of the beta-hex A gene revealed the G269S mutation as the most common disease allele; found in homozygosity (N = 1) or heterozygosity (N = 18; including 2 sib pairs). Disease onset (age 36 years) was delayed and progression relatively slower in the homozygous G269S patient. Two siblings (ages 28 and 31 years), of non-Jewish ancestry, were compound heterozygotes (TATC1278/W474C); their clinical course is dominated by psychiatric problems. Brain imaging studies revealed marked cerebellar atrophy in all patients (N = 18) tested, regardless of disease stage. CONCLUSIONS: Late-onset Tay-Sachs disease is an infrequent disorder and the diagnosis is often missed or delayed (by approximately 8 years). Early on, the majority of patients develop signs of either cerebellar or anterior motor neuron involvement. Affected individuals may also develop psychotic episodes. In most cases, the later-onset of expression results from the presence of at least one allele (usually the G269S mutation), associated with residual enzyme (beta-hexosaminidase A) activity. A positive family history is a valuable clue, enabling early diagnosis. Nonspecific cerebellar atrophy on brain imaging is another important finding. This entity should be considered among patients presenting with speech, gait, and balance problems, and those with psychiatric disorders even when focal neurologic deficits may be initially absent. Accurate diagnosis will permit appropriate genetic counseling regarding disease prognosis and reproductive risks.

Adolescent↗

PubMed2005

Developmental outcome of epilepsy surgery in tuberous sclerosis complex.

In Tuberous sclerosis complex (TSC), neurological dysfunction, usually in association with epilepsy, is responsible for the greatest degree of disease-related disability. Epilepsy surgery is increasingly recognized as a therapeutic option given the often medication-resistant nature of the disease. Seven subjects with medically refractory epilepsy associated with TSC, who underwent surgery at a tertiary care epilepsy center and in whom both preoperative and postoperative neuropsychological data were available, were examined. The Vineland Adaptive Behavior Scales, and in one case, the WISC-III were utilized. Postoperatively, the composite standard scores declined in six of the seven subjects, although for the most part this decline was quite modest (8 points or less in 5/6 subjects). The mean overall developmental/intellectual quotients were comparable across assessments (preoperative M = 55, SD = 20.3; postoperative M = 49 SD = 16.6). Good outcomes appeared to be related to seizure relief. Age estimates of developmental level indicated developmental progress in the majority of subjects in the current sample, and may yield greater clinical information for individuals with developmental delay than do standard scores.

Adult↗

PubMed2004

Group psychoeducation as treatment for psychological nonepileptic seizures.

There is no consensus for the type(s) of treatment(s) that may be effective or ineffective for psychological nonepileptic seizures (PNES). We provided an open-ended group psychotherapy program to 10 patients with PNES, including a disorder-specific psychoeducation treatment component in the first 10 weeks. Seizure frequency and questionnaire responses were examined pre- and posttreatment in all 7 of 10 individuals who completed the majority of the psychoeducational sessions. Four individuals experienced no change in seizure frequency; in three of these this was due to a cessation of events at treatment initiation. Two individuals experienced a decline; and one, an increase, in seizure frequency. Significant decreases were reported in posttraumatic (P=0.003) and dissociative (P=0.04) symptoms and emotionally based coping mechanisms (P=0.03). There was also a trend toward improved quality of life (P=0.07). Experience/expression of anger remained stable. Psychoeducation may be an effective method of treating PNES and may improve coping strategies and reduce PNES-associated psychopathology in some patients. Additional controlled studies on larger samples are needed.

Adult↗

PubMed2004

Cognitive and behavioral correlates of tuberous sclerosis complex.

Tuberous sclerosis complex is a multisystem disorder in which neurologic problems cause the greatest disability. High rates of mental retardation and autism spectrum disorders are associated with the diagnosis. Early-onset seizures and increased tuber burden are risk factors for cognitive impairment. Early-onset seizures, particularly infantile spasms, are risk factors for autism. Tubers within the temporal lobe and cerebellum are often mentioned as risk factors for autism, although the findings are inconsistent. Seizure control is important for developmental outcome and quality of life. Early behavioral assessment and therapeutic intervention, as well as seizure control, are the most effective means of promoting neurodevelopmental outcome.

Anticonvulsants↗

PubMed2003

Variation in stereoacuity: normative description, fixation disparity, and the roles of aging and gender.

PURPOSE: Variation in stereoacuity was examined in a large group of observers with Snellen acuity of 20/30 or less. METHODS: Threshold retinal disparity for 2.78 degrees x 2.28 degrees rectangular test stimuli was determined as a function of the retinal disparity (varied from 55 arcmin uncrossed to 55 arcmin crossed) of a 5.57 degrees x 4.8 degrees rectangular pedestal stimulus in 160 observers 15 to 79 years of age. In most cases, data were collected during viewing of random dot stereograms (RDSs) presented for 100-ms, which prevents involvement of vergence or monocular depth cues. RESULTS: When plotted logarithmically, 100-ms thresholds in 106 observers less than 60 years of age approximated a normal distribution (mean, 1.57 +/- 0.227 [SD] log arcsec [37 linear arcsec]). Among these, one observer was supernormal, 88% were within the normal range (+/-2 SD of the log mean), 2% had elevated thresholds, and 8% failed testing with 100-ms stimuli but had residual binocular depth discrimination; 1 observer was stereoblind. In contrast, only 37% of the observers aged 60 to 69 and 25% of the observers aged 70 to 79 had stereoacuity within the normal range. Moreover, the extent of the stereo deficiencies became more pronounced with age. Fixation disparity was operationally defined as optimal stereoscopic threshold with a nonzero retinal disparity pedestal. Of the 151 normal observers tested, 89% were maximally sensitive to disparities within 11 arcmin of fixation: all males were maximally sensitive to pedestals within 22 arcmin of fixation, whereas 8% of females had fixation disparities of more than 22 arcmin. Males were more likely to be sensitive with uncrossed-disparity pedestals, whereas females were more likely to be sensitive with crossed disparity. CONCLUSIONS: Age-related deterioration in stereoacuity is reflected not only by a linear correlation between age and threshold but also by a catastrophic factor that produces more marked deterioration after age 60. Both factors are probably cerebral and not specifically related to stereopsis. The prevalence of fixation disparity in the normal population is probably more common than previously reported.

Adolescent↗