Search PubMed⌕ Search

Biomedical subjects

M B Denckla

Publications and source records attributed to M B Denckla.

At least 55 records · Page 3Linked to original sources
PubMed1995

Neurodevelopmental effects of the FMR-1 full mutation in humans.

Brain dysfunction is the most important sequelae of the fragile X (FMR-1) mutation, the most common heritable cause of developmental disability. Using magnetic resonance imaging (MRI) and quantitative morphometry, we have compared the neuroanatomy of 51 individuals with an FMR-1 mutation with matched controls and showed that subjects with an FMR-1 mutation have increased volume of the caudate nucleus and, in males, the lateral ventricle. Both caudate and lateral ventricular volumes are correlated with IQ. Caudate volume is also correlated with the methylation status of the FMR-1 gene. Neuroanatomical differences between two monozygotic twins with an FMR-1 mutation who are discordant for mental retardation are localized to the cerebellum, lateral ventricles and subcortical nuclei. These findings suggest that the FMR-1 mutation causing the fragile X syndrome leads to observable changes in neuroanatomy that may be relevant to the neurodevelopmental disability and behavioural problems observed in affected individuals.

Adolescent↗
PubMed1995

An analysis of two discrepancy-based models and a processing-deficit approach in identifying learning disabilities.

The incidence of learning disabilities (LD) in a research center sample of 107 boys and 103 girls between 6 and 12 years of age was calculated using Wechsler IQ and Woodcock-Johnson cluster scores in a regression model (REG) and a reliability model (REL). The REL method identified LD three times more often than the REG method, and all those identified by REG were also identified by REL. When stratified by IQ, REG and REL identified similar percentages in the lowest IQ group; however, REG identified at a lower rate as IQ increased. All 87 children identified with reading disabilities (both REL-RD and REG-RD) were weak to a similar extent on phonemic awareness. Comorbid elevated attention ratings were found in 62% of children with RD; 26% had elevated attention ratings but no linguistic processing deficits, and 21% had at least one linguistic processing deficit but no attentionally suspect rating.

Attention Deficit Disorder with Hyperactivity↗
PubMed1995

Learning difficulties in children with Tourette syndrome.

Children with Tourette syndrome have been shown to have a variety of school difficulties. These difficulties, however, may be related to a single factor or to a combination of problems including tic severity, the use of tic-suppressing medication, executive dysfunction, a direct consequence of having a stigmatizing disorder, and coexisting attention deficit disorder, hyperactivity, obsessive-compulsive behaviors, or other psychopathologies. The goals for the treating health care team are to identify the presence of these factors, to clarify which are the major source of distress, and to develop an individualized multimodal treatment program. The prompt diagnosis of underlying problems and the prescription of appropriate therapy can play an important role in preventing school failure in children with Tourette syndrome.

Adrenergic alpha-Agonists↗
PubMed1995

The treatment of attention-deficit hyperactivity disorder in Tourette's syndrome: a double-blind placebo-controlled study with clonidine and desipramine.

OBJECTIVES: Because psychostimulants can exacerbate preexisting motor/phonic tics in individuals with Tourette's syndrome (TS), a clinical trial was performed to examine the ability of clonidine and desipramine to modify attention-deficit hyperactivity disorder (ADHD) behaviors in children with TS + ADHD. METHODS: A double-blind, placebo-controlled protocol was used in which each subject served as his or her own control and received, in a randomly assigned fashion, 6-week medication cycles with clonidine (0.05 mg four times daily), desipramine (25 mg four times daily), and placebo. RESULTS: Thirty-seven children with TS+ADHD between the ages 7 to 13 years and of normal intellect were recruited, and 34 (31 males, 3 females) completed the entire protocol. Outcome measures for ADHD included Parent and Teacher Child Behavior Checklists (CBCL), continuous performance tests, and neuropsychologic tests of executive function. Several markers for ADHD were shown to improve significantly (P < .05) after treatment with desipramine (parent linear analogue rating, parent CBCL "hyperactivity" subscale, and teacher CBCL subscales "nervous/overactive," "anxious," and "unpopular"). Improvement with desipramine was always superior to that noted with clonidine. Clinical improvement did not correlate with drug blood levels. On measures of tic severity, neither drug made tics worse. Desipramine showed a statistically significant improvement on a global linear analogue scale, but not on the Hopkins Motor/Vocal Tic Severity Scale, the Tourette Syndrome Severity Scale, or the Yale Global Tic Severity Scale. Clonidine did not significantly alter tic severity on any measure. CONCLUSION: The results of this study suggest that desipramine may be a useful alternative for the treatment of symptoms of ADHD in children with TS.

Adolescent↗
PubMed1994

Molecular-neurobehavioral associations in females with the fragile X full mutation.

In this study, young females with the fragile X [fra(X)] full mutation (fM) were assessed using quantitative measures of mutation amplification size (Amp) as well as the ratio of active normal X chromosome to total normal X chromosome (activation ratio-AR). Neurobehavioral assessments of females with the fM were performed and included specific and general measures of cognitive and behavioral/developmental functioning. To investigate molecular-behavioral associations, Amp and AR were used as independent variables, while cognitive and behavioral scores were used as dependent variables. Significant correlations were observed between both molecular variables (Amp and AR) and measures of cognitive functioning, with AR showing the most consistent and robust correlations. As AR increased, overall IQ and specific subtest and area scores from the cognitive tests increased. Conversely, as Amp increased, the overall IQ and specific subtest and area cognitive scores decreased. No significant associations were observed between AR or Amp and measures of behavior or development. The molecular-cognitive associations were generally consistent with the cognitive profile previously described in studies comparing females with fra(X) to age-matched controls. Amp and AR were not associated with one another, nor were they associated with the same cluster of cognitive measures. Though this report does not conclusively show that AR and Amp can be used to clinically assess the risk of a female with the fM for cognitive disability, the evidence presented does suggest that these molecular variables, especially AR, reflect important underlying genetic factors contributing to the fra(X) phenotype.

Adolescent↗
PubMed1994

Neurofibromatosis type 1: the cognitive phenotype.

Visuospatial deficits have been reported in patients with neurofibromatosis type 1 (NF 1), although detailed observations regarding academic achievement are conflicting. Using neurocognitive testing and magnetic resonance imaging, we studied 12 families, each comprising one child with NF 1, an unaffected sibling of the same age range (6 to 16 years), and both biologic parents. The Full Scale IQ ranged from 70 to 130 among children with NF 1 and from 99 to 139 among unaffected siblings. A significant (p < 0.01) pairwise difference was found between each child with NF 1 and sibling on the Full Scale IQ and the Verbal IQ. On a single visuospatial test, Judgement of Line Orientation, children with NF 1 did significantly worse than siblings (p < 0.01). Children with NF 1 had significant learning disabilities in written language and reading (p < 0.05) and in neuromotor dysfunction (p < 0.005) compared with siblings. A significant correlation was found between the pairwise lowering of the Full Scale IQ and Judgment of Line Orientation scores in children with NF 1 and the number of locations in which, on magnetic resonance imaging, T2-weighted hyperintensities were seen (Full Scale IQ: p < 0.0003; Judgment of Line Orientation score: p < 0.02). We conclude that NF 1 is associated with a significantly lower Full Scale IQ, multifocal cognitive deficits (Verbal IQ, Judgment of Line Orientation score), reading disability, and neuromotor deficit. Pairwise cognitive differences correlated with the number of brain lesions on magnetic resonance imaging.

Adolescent↗
PubMed1994

Developmental dyslexia and attention dysfunction in adults: brain potential indices of information processing.

Event-related brain potentials (ERPs) were recorded from a group of 13 men with severe developmental dyslexia and 15 matched normal controls. Auditory and visual stimuli, presented in separate reaction time tasks of graded difficulty, were used to elicit ERPs. No group differences in P300 were seen under relatively undemanding task conditions. However, as task demands increased, visual P300 was reduced in the dyslexic men as compared with the normal readers. An Abbreviated Conners Parent Rating Scale was used to assess retrospectively childhood symptoms of attention-deficit hyperactivity disorder (ADHD). Additional analyses revealed that the dyslexics with a history of many symptoms of ADHD in childhood (high ADHD) accounted for the group differences in P300; the dyslexics with a history of few or no such symptoms (low ADHD) were indistinguishable from the controls at all electrode sites. Furthermore, whereas the low-ADHD dyslexics showed the same hemispheric asymmetry in auditory P300 as did the controls (right > left), auditory P300 was more symmetrically distributed in the high-ADHD dyslexics. The results are interpreted as suggesting that a distinct brain organization may characterize dyslexic men with a history of concomitant deficits in attention.

Adult↗
PubMed1994

Neurofibromatosis type 1: the evolution of deep gray and white matter MR abnormalities.

PURPOSE: To investigate the evolution of deeply located high-signal-intensity abnormalities of the brain on T2-weighted MR images of patients with neurofibromatosis type 1 (NF-1). METHODS: The study consists of two patient groups: 1) retrospective evaluation of MR scans of 24 symptomatic NF-1 patients, 10 of whom were sequentially studied, and 2) prospective MR evaluations of 20 asymptomatic NF-1 subjects from 14 families; 2 of these families were sequentially studied. RESULTS: Deeply located, high-signal-intensity abnormalities on T2-weighted images were noted in 34 of 44 NF-1 subjects (77%). If NF-1 patients are grouped according to age, 28 of 30 subjects (93%) younger than 15 years had the lesions, whereas 4 of 7 subjects (57%) between 16 and 30 years, and 2 of 7 subjects (29%) older than 31 years had lesions. High-signal lesions in basal ganglia and brain stem were demonstrated in all decades with relatively high frequency. Lesions in the cerebellar white matter and dentate nuclei were mainly found in the patients younger than 10 years, and never found after the third decade. In 13 sequential studies (mean interval, 24 months), lesions appeared to increase in size in 3, remain unchanged in size in 2, and decrease in size in 7. One subject showed a mixed pattern of lesion size change. CONCLUSIONS: Deeply located high-signal-intensity lesions on T2-weighted MR images are more evident in young NF-1 patients. The underlying brain abnormality, while pathologically unproved, is probably transient.

Adolescent↗
PubMed1993

Locomotion of autistic adults.

OBJECTIVE: To assess gait in patients with autism. DESIGN: Clinical and physiologic assessment. SETTING: Research hospital. PATIENTS AND SUBJECTS: Five adults with autism and five healthy, age-matched control subjects. MAIN OUTCOME MEASURE(S): Clinical and biomechanical assessment. RESULTS: Clinical assessment showed mild clumsiness in four patients and upper limb posturing during gait in three patients. The velocity of gait, step length, cadence, step width, stance time, and vertical ground reaction forces were normal in all patients. The only significant abnormality was decreased range of motion of the ankle. Some patients exhibited slightly decreased knee flexion in early stance. Clinically, the gait appeared to be irregular in three patients, but the variability was not significantly increased. CONCLUSIONS: The findings in patients with autism indicate a nonspecific, neurological disturbance involving the motor system. The normal velocity of gait and the normal step length argue against a parkinsonian-type disturbance, whereas the clinical picture suggests a disturbance of the cerebellum.

Adult↗
PubMed1993

The effects of X monosomy on brain development: monozygotic twins discordant for Turner's syndrome.

Monosomy for the X chromosome is the most frequent cause of Turner's syndrome, a common clinical syndrome associated with particular physical and neurobehavioral features. The results from comprehensive assessment of prepubertal monozygotic female twins discordant for X monosomy are presented. Zygosity was established with DNA Fingerprinting and no evidence of chromosomal mosaicism was seen in either child. Physical features in the affected twin were relatively mild with respect to the full spectrum of physical malformations and disabilities associated with Turner's syndrome. The neurobehavioral phenotypes of the twins were compared. Although both sisters scored in the superior range of intelligence, the affected twin's Performance IQ was 18 points less than her sister, whereas Verbal IQ showed only a 3-point difference between the sisters. Other relative differences were noted within the executive, visuospatial, and visuomotor domains of function. Behavioral evaluation indicated greater problems with attention, hyperactivity, and anxiety in the affected twin. Quantitative analysis of brain anatomy revealed evidence of both general and regional effects of X monosomy on neurodevelopment. Cerebrospinal fluid volume was increased by 25% in the affected twin compared with her sister with a corresponding decrease in gray matter volume. The right frontal, right parietal-occipital, and left parietal-perisylvian regions showed the greatest discrepancy between the sisters with respect to increased cerebrospinal fluid and decreased gray matter volumes in twin with X monosomy. Differences in the posterior fossa were also noted with a 50% relative increase in the volumes of the fourth ventricle and cisterna magna and a 10 to 15% relative reduction in size of the cerebellar vermis, pons, and medulla in the affected twin. The association between the neurobehavioral and neuroanatomical findings in the affected twin is discussed. The unique nature of the naturally occurring genetic phenomenon seen in this twin pair provides an opportunity to more fully elucidate the neurobehavioral phenotype associated with X monosomy and Turner's syndrome.

Brain↗
PubMed1993

The child with developmental disabilities grown up: adult residua of childhood disorders.

A clinic specializing in learning disabilities and willing to assess adults receives referrals that parallel the three major reasons for referral in the pediatric and adolescent school-aged population: (1) "Is this patient dyslexic"; (2) "Does this patient 'have' ADHD residual type"; (3) "Does this patient have some kind of learning disability?" The third is the most difficult and least well understood, the NVLD or so-called right-hemisphere group, most likely to be referred by mental health facilities and professionals. The first, dyslexia, has the most secure neuroscientific background and in some ways the most straightforward conceptualization yet is still controversial in terms of the subtle and well-masked ways in which its manifestations may be seen. Aptly placed in the second and hence middle position, straddling both dyslexia and NVLD, is that sprawling and emphatically heterogeneous collection of observations agglomerated under the title ADHD and affiliated with the pharmacotherapy of stimulants. Yet for all its sprawl, ADHD stands in relation to its cognitive overlap zone, executive dysfunction, as symptoms do to signs; and executive dysfunction, especially in adults, appears to be a cognitive-deficit cluster of special importance to the persistence of uncompensated or clinically significant learning disabilities. That is, the real question to be answered about adults with learning disabilities is why have they not compensated for cognitive deficits; or, if they have acquired basic academic skills, why have they not been able to use these skills? Unless linguistic or spatial deficits are extremely severe, academic skills can usually be acquired by compensatory strategies and, once acquired, can be used. Ability to compensate (and to generalize the compensation) are crucial determinants of adult learning disabilities outcome. Less is understood about nonacademic skills, of which the social domain seems least optional, i.e., most pervasively important. Spatially based skills are the least difficult to avoid or circumvent. Absent severe linguistic or spatial cognitive deficits, the most central neuropsychologic issues in adult learning-disability studies are executive dysfunction and social imperception/ineptitude. At present, executive dysfunction is the one of these two that can be evaluated in a behavioral neurology clinic.

Adult↗
PubMed1991

Neurological disease in xeroderma pigmentosum. Documentation of a late onset type of the juvenile onset form.

Xeroderma pigmentosum (XP) is an autosomal recessive, neurocutaneous disorder characterized by sunlight-induced skin cancers and defective DNA repair. Many XP children develop a primary neuronal degeneration. We describe 2 unusual XP patients who had a delayed onset of XP neurological disease. Somatic cell genetic studies indicated that they have the same defective DNA repair gene and are both in XP complementation group A. These 2 patients, together with a group A patient previously reported from London, establish as a distinct clinical entity the late onset type of the juvenile onset form of XP neurological disease. The functional capacity of these patients' cultured fibroblast strains to survive after treatment with ultraviolet radiation indicates that their DNA repair defect is less severe than that of typical group A patients who have a more severe neurodegeneration with an earlier symptomatic onset. The premature death of nerve cells in XP patients (which is presumably due to their inherited defects in DNA repair mechanisms) suggests that normal repair of damaged DNA in neurons is required to maintain integrity of the human nervous system.

Adolescent↗
PubMed1991

Attention deficit hyperactivity disorder-residual type.

Evidence for the persistence into adult life of attention deficit hyperactivity disorder (ADHD) has accumulated in publications of the past two decades. As reviewed here, retrospective and longitudinal data suggest that a residual type of ADHD (ADHD-RT) can be recognized. Diagnostic historical interview and checklist criteria, primarily the Utah set developed by Wender and colleagues, have been proposed. The difficulties of obtaining reliable and valid historical information, which are greater than those encountered in diagnosing childhood cases, add to the desirability of some direct examination for ADHD-RT. It is proposed herein that assessment of the neuropsychological domain of executive function--broader than, yet encompassing, several facets of attention--offers opportunities for documentation of the cognitive correlates of ADHD-RT, its responsiveness to therapeutic intervention, and clues as to its neurobiological foundation.

Adult↗
PubMed1989

EEG spectra in severely dyslexic men: rest and word and design recognition.

To identify and localize differences in brain functioning, electrical activity was recorded with a full complement of scalp electrodes in 14 healthy, severely dyslexic men (mean age = 22 years, S.D. = 3) and 15 matched controls during rest and during word and design recognition. The electroencephalograms were spectrum analyzed, and the mean amplitude in each of 5 bands--delta, theta, alpha, slow beta and fast beta--compared topographically between conditions and groups. The two tasks did not elicit differentially lateralized patterns of electrical activity, but produced anteroposterior differences in alpha and theta. The Designs task, more difficult for both groups, was associated with less posterior alpha than was the Words task. The strongest group difference was likewise seen along an anteroposterior axis on the Designs task. With performance equal to that of controls, the dyslexics showed relatively greater fronto-central theta and less posterior theta (a more activated state), suggesting that dyslexics were compensating for less efficient information processing. There were no group differences in overall amplitude in any band for any condition. The differences in the topographic distribution of theta may reflect subtle differences in brain organization or compensatory recruitment of widely distributed neuronal networks.

Adult↗
PubMed1989

Reliability of subtle (soft) neurological signs in children.

Reliability and stability of neurological "subtle" ("soft") signs were assessed in 54 psychiatric patients and 25 normal children, aged 5-17 years, using the revised Neurological Examination for Subtle Signs (NESS). Acceptable interrater reliability (kappa greater than or equal to 0.50, or intraclass correlation coefficient greater than or equal to 0.70) was found for 40 of the 64 items tested. Test-retest reliability at 2 weeks was unsatisfactory for most of the categorically scored items, including some "classic" subtle signs such as overflows or dysrhythmias. Continuous items, such as time needed to perform 20 consecutive movements, remained mostly stable at retest. A practicing effect was evident only in the graphesthesia test. Overall internal consistency was good (Cronbach's alpha = 0.74). Given the poor stability of overflows and dysrhythmias, researchers and clinicians should rely more on subtle signs that can be assessed on continuous scales.

Adolescent↗
PubMed1989

Neurofibromatosis type 1 (Recklinghausen's disease). Neurologic and cognitive assessment with sibling controls.

Neurologic and cognitive function in neurofibromatosis type 1 (NF1) were assessed in a controlled pilot study of 13 pairs of siblings aged 6 to 27 years. One subject in each pair was affected with NF1, and the other, the control subject, was unaffected. Subjects with evidence of focal central nervous system disease were excluded. The 13 subjects with NF1 had no excess of mental retardation, attention-deficit disorder, or specific learning disorders (using Wilcoxon's Signed Rank Test and McNemar's Test for Symmetry). These subjects, however, had significantly higher scores for subtle neurologic abnormalities (21 vs 6) and significantly lower full-scale IQ scores (94 vs 105) than their unaffected siblings. The IQ scores of the affected subjects were not clustered at the lower end of the scale but showed a slight downward shift in distribution compared with those of their siblings. In addition, a visual-spatial orientation deficit was present in eight of nine affected subjects so evaluated. The findings suggest that subjects with NF1 have a widespread alteration of the brain during development that manifests as one or more specific types of neuropsychologic deficits.

Adolescent↗
PubMed1988

Neurophysiological studies in dyslexia.

Using sophisticated computer graphics technologies and sensitive methods, our original dyslexia study of dyslexic boys delineated specific areas of the brain which in combination could constitute a "physiological signature" of dyslexia. In addition to identifying aberrant brain function in the traditional language-associated left posterior region, we also observed medial frontal lobe differences from normals, a finding confirmed by others in recent research. Our subsequent study sought to refine further current definitional subgroupings within the broad entity known as dyslexia-pure. Indeed language-based subgroups appear to have identifiable and differing topographic signatures. Furthermore, based on correlations between neuropsychological test scores and neurophysiological measurements, we suggest that subgroup electrophysiological differences may reflect compensatory as well as pathological brain activity. We believe that the currently expanding understanding of the neurophysiology of dyslexia will lead eventually to improved diagnosis and remediation of this learning disability. The detailed mapping of brain electrical activity shows promise of providing the neuropsychologist and learning disability specialist with another "perspective" on reading disability. This technique may prove valuable in the diagnosis of dyslexia at an early age and in the tailoring of the learning experience to a child's specific deficits and capabilities.

Brain↗