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Biomedical subjects

A K Percy

Publications and source records attributed to A K Percy.

At least 73 records · Page 4Linked to original sources
PubMed1990

Rett syndrome and associated movement disorders.

Rett syndrome, a progressive neurodegenerative disorder described only in female subjects, is manifested by a wide spectrum of behavioral and motor abnormalities. We studied 32 patients with this disorder, ages 30 months to 28 years old, and characterized their extrapyramidal disturbance. The most common motor abnormalities were stereotyped movements and gait disturbance, seen in all patients. Bruxism, oculogyric crises, parkinsonism, and dystonia were also common, but myoclonus and choreoathetosis were seen only infrequently. The hyperkinetic movement disorders tended to dominate in younger patients, while bradykinetic disorders were more evident in the older patients. This study provides evidence that movement disorders seen in Rett syndrome reflect age-related neurodegenerative changes in the basal ganglia.

Adolescent↗
PubMed1990

The Rett syndrome program project at Baylor College of Medicine.

The Baylor Rett syndrome (RS) program project has enrolled more than 60 of the anticipated 70 children to be evaluated over 5 years. The program is composed of 6 individual projects and a Core center for coordinating the evaluations and managing the data. The projects consist of I) Clinical assessment of RS; II) Status of communication skills in RS; III) Clinical neurophysiology and sleep in RS; IV) Epidemiology of RS; V) Molecular genetics in RS; and VI) Neuropathology of RS. This program project and a similar program at the Johns Hopkins University School of Medicine are complementary.

Clinical Trials as Topic↗
PubMed1990

Patterns of X chromosome inactivation in the Rett syndrome.

The Rett syndrome (RS) is a degenerative neurological disorder occurring exclusively in young females. The disorder is sporadic in the majority of the cases, however a few familial cases with inheritance through maternal lines have been identified. Based on these observations the condition could be due to an X chromosome mutation which is lethal in males. To explain the familial cases, a hypothesis of possible non-random X inactivation is proposed. To investigate the possibility of non-random X chromosome inactivation in RS, we carried out analysis using restriction fragment length polymorphisms (RFLPs) and methylation sensitive enzymes at the PGK and HPRT loci. The results show that there is increased incidence of non-random X chromosome inactivation in peripheral blood leukocytes in sporadic RS patient (36%), as compared to healthy controls (8%). Using brain tissue from three patients, only a random pattern was detected, although varying degrees of skewing were detected in the peripheral tissues of these patients. Analysis of leukocyte DNA from a mother of two affected half-sisters revealed non-random X chromosome inactivation suggesting a possible selection against RS allele. Additional familial cases of RS should be evaluated to determine if this observation is common to all female carriers. If non-random X chromosome inactivation occurs in all the putative "carriers," this would be the first evidence to support the hypothesis of an X linked mutation which is lethal in males.

Dosage Compensation, Genetic↗
PubMed1990

Determination of gangliosides in six human primary medulloblastomas.

The ganglioside composition of six human medulloblastomas was analyzed. The characterization was performed by thin-layer chromatography, sialidase hydrolysis, and immunological staining with a panel of characterized antiganglioside monoclonal antibodies. The total ganglioside content ranged from 60 to 1,130 nmol of ganglioside sialic acid/g wet weight. Neuronal gangliosides (gangliotetraose series) were found in varying amounts in all medulloblastomas. Gangliosides of the neolactotetraose series (3'-LM1 and LD1) were present in all specimens, and the lactotetraose series ganglioside 3'-isoLM1 was found in all cases showing astrocytic differentiation. This supports our previous findings that 3'-isoLM1 is a marker for proliferating astroglial cells.

Adolescent↗
PubMed1990

Rapidly progressive type III Gaucher disease: deterioration following partial splenectomy.

Total splenectomy has been found to accelerate disease progression in Type III Gaucher disease, therefore partial splenic resection was performed in a 28 month old girl with rapidly progressive (non-Norrbottnian) Type III disease to alleviate the effects of hypersplenism. Surgery failed to arrest the disease process and splenomegaly recurred within three months. The erythrocyte glucosylceramide level increased post-operatively. Post-mortem studies revealed dense accumulation of Gaucher cells in spleen, liver, lungs, bone marrow and within the central nervous system. The glucosylceramide content of brain and liver was elevated to the range previously noted in splenectomised Norrbottnian patients. Thus, in rapidly progressive Type III Gaucher disease, neither total nor partial splenectomy alone provides a favourable outcome.

Child, Preschool↗
PubMed1990

Extrapyramidal involvement in Rett's syndrome.

Extrapyramidal dysfunction is poorly characterized in Rett's syndrome, a neurodegenerative disorder in girls. We studied the motor and behavioral findings in 32 Rett's syndrome patients, 21 months to 30 years old. In addition to the typical stereotyped movements and scoliosis, other motor disturbances included bruxism, sialorrhea, ocular deviations, parkinsonian findings, dystonia, myoclonus, and athetosis. The types of movement disorders seemed to be age-related, with the hyperkinetic disorders occurring in the younger patients and the bradykinetic disorders occurring more frequently in the older patients.

Adolescent↗
PubMed1989

Cerebrospinal fluid biogenic amines and biopterin in Rett syndrome.

We evaluated cerebrospinal fluid biogenic amine metabolites in 32 patients with Rett syndrome. Significant reductions were noted in the metabolites of norepinephrine, dopamine, and serotonin, as compared with controls of similar age (p less than 0.001, p less than 0.001, and p less than 0.05, respectively). Tetrahydrobiopterin is an essential cofactor and may be rate-limiting for the synthesis of catecholamines and serotonin. Accordingly, total cerebrospinal fluid biopterin was measured and found to be elevated in patients compared with controls (p less than 0.002). These findings constitute the only biochemical changes detected in Rett syndromes so far.

Adolescent↗
PubMed1989

Chiari type I malformation in children.

We reviewed the recent experience at Texas Children's Hospital by examining the records of 11 children who underwent suboccipital decompression for symptomatic Chiari type I malformation. Presenting complaints included neck pain (1 child), scoliosis (4 children), back pain (1 child), torticollis (1), motor dysfunction (1), and apnea (3 children). Neurologic findings were normal in 7 of the 11 children. The craniocervical junction and medulla were studied by magnetic resonance imaging, which revealed anatomy consistent with Chiari type I malformation in all cases. At surgery, all patients had tonsillar herniation to the first cervical vertebra or below. Three patients had syringomyelia. Postoperatively, either the patients were symptom free or, in the cases of scoliosis and torticollis, there was no progression. Our experience suggests that Chiari type I malformation may occur in childhood with varied and unusual clinical findings. Magnetic resonance imaging was essential to the diagnosis; the presence of tonsillar herniation was confirmed at surgery. The results of suboccipital decompression were favorable in this series.

Adolescent↗
PubMed1988

Neuropathology of Rett syndrome.

Rett syndrome is an increasingly recognized progressive disorder in females, commencing in infancy and characterized by autistic behavior, gait ataxia, stereotyped movements, seizures and generalized growth and mental retardation, possibly associated with disorders of central biogenic amine synthesis. The gene locus and pathogenesis of Rett syndrome are unknown. Autopsy studies in nine girls dying between 4 and 17 years, and sural nerve and muscle biopsies from two girls aged 3 and 17 years showed: (1) diffuse cortical atrophy/micrencephaly, with a decrease in brain weight by 12% to 34% of age-matched controls, apparently related to the duration of the disorder; (2) mild diffuse cortical atrophy with increased amounts of neuronal lipofuscin and occasional mild gliosis, but without signs of a storage disorder; (3) underpigmentation of the zona compacta nigrae, which showed fewer well-pigmented neurons for age and fewer melanin granules per neuron, while total numbers of nigral neurons and the substructure of neuromelanin were normal for age. No pathological changes were seen in other transmitter-specific brain stem nuclei; (4) immunoreactivity for tyrosine hydroxylase was slightly reduced in nigral and hypothalamic neurons, and the pituitary gland showed decreased immunoreaction for prolactin and growth hormone; (5) ultrastructurally, in frontal cortex and caudate nucleus, isolated abnormal neurites and reactive or degenerative axonal swellings were seen; the latter are possibly related to the nigral changes, suggesting some dysfunction of the dopaminergic nigrostriatal system, which is supported by neurochemical data; (6) preliminary biochemical studies revealed increased beta-endorphines in thalamus and cerebellum; (7) peripheral nerves demonstrated increase in small fibers without demyelination and increased numbers of neurofilaments in axons, suggesting distal axonopathy, while skeletal muscle showed alterations in the sarcoplasmic reticulum with circular profiles in the Z-filaments. These nonspecific changes may be interpreted as early signs of denervation. The variety of lesions in the central, neuroendocrine and peripheral neuromuscular systems in Rett syndrome are discussed with regard to their clinical and biochemical significance.

Adolescent↗
PubMed1988

Rett syndrome: qualitative and quantitative differentiation from autism.

Patients with Rett syndrome appear to fulfill the Rendle-Short criteria for the diagnosis of autism, but the pattern of their behavior is qualitatively different from children with autism. Until a biologic marker is identified, diagnosis is based on clinical assessment. In order to standardize this clinical assessment and to provide objective criteria for the evaluation of potential therapeutic modalities, motor and behavioral characteristics of 15 Rett patients were analyzed. The patients with Rett syndrome differed from autistic children in having ataxia, breath-holding, hyperventilation, bruxism, simplicity of stereotypies, and hand apposition. The children with autism demonstrated complex stereotypies and verbal but not motor regression. The more typical features of autism, namely, poor eye contact, lack of sustained interest, speech disturbance, and repetitive truncal rocking motions were poor discriminators between the two groups.

Adolescent↗
PubMed1988

Research in Rett syndrome: past, present, and future.

Past, present, and future research activities in Rett syndrome are described. Studies to this point have failed to define a biologic or chemical marker. It is hoped that heightened activity in this unique syndrome will provide guidance for the diagnosis of this disorder, and with it, better understanding.

Ammonia↗
PubMed1988

Recommendations regarding handling of the necropsy in Rett syndrome.

In order to maximize biochemical, neurochemical, molecular, and pathologic information from patients with Rett syndrome, a uniform procedure has been developed for the conduct of the postmortem examination. Tissue should be prepared for freezing, for electron microscopy studies, and for standard histologic examination. For the purposes of uniformity, three central repositories for necropsy materials have been established and are available at all times. In the event of the death of a patient with Rett syndrome, parents who consent to necropsy should request that materials be handled according to the protocol and transported under appropriate conditions to the central repository. The National Neurological Research Bank (Los Angeles), the Brain Tissue Bank (Belmont, Mass), and the Department of Neuropathology at Johns Hopkins Hospital (Baltimore) have agreed to serve as repositories for tissues. A committee of the International Rett Syndrome Association medical advisory panel will monitor this process in cooperation with the directors of the respective tissue banks.

Ammonia↗
PubMed1987

Rett's syndrome. Correlation of electroencephalographic characteristics with clinical staging.

Rett's syndrome is a progressive disorder in female patients, characterized by autistic behavior, dementia, ataxia, loss of purposeful use of the hands, and seizures. The electroencephalographic (EEG) characteristics of 17 patients with Rett's syndrome, studied between the ages of 1 and 16 years, are reported and correlated with a recently proposed system of clinical staging. Although a specific diagnostic EEG pattern was not seen in these patients, we did observe a progressive deterioration in the EEG, characterized by a slowing of EEG activity, a loss of normal sleep EEG characteristics, and the appearance of multifocal epileptiform abnormalities, followed by a pattern of generalized slow spike-wave activity. These characteristics appear to be typically seen in patients with Rett's syndrome and can be correlated with clinical staging. The EEG may be of benefit in identifying variations or subgroups in patients with Rett's syndrome as a complement to the clinical examination.

Adolescent↗
PubMed1987

Rett's syndrome: characterization of respiratory patterns and sleep.

Rett's syndrome is a progressive disorder that occurs in females and is characterized by autistic behavior, dementia, ataxia, loss of purposeful use of the hands, and seizures. Patients with Rett's syndrome have been observed to have stereotyped hand movements (hand-washing) and to exhibit intermittent hyperventilation. To characterize more precisely the sleep and respiratory patterns associated with this disorder, polygraphic studies were made during sleep and wakefulness in 11 patients with this syndrome. These studies showed abnormal respiratory patterns during wakefulness, and abnormal sleep and electroencephalographic characteristics. The patients had decreased percentages of rapid-eye-movement sleep, and during wakefulness, a pattern of disorganized breathing was observed in all 11 patients and consisted of hypoxia followed by a period of increased respiratory rate and effort. The occurrence of disorganized breathing and compensatory hyperpnea during wakefulness with regular, continuous breathing during sleep is characteristic of Rett's syndrome and suggests an altered or impaired voluntary/behavioral respiratory control system.

Adolescent↗
PubMed1987

Rett syndrome: discrimination of typical and variant forms.

Eighteen female patients are described with the clinical features of Rett syndrome. Fifteen patients fulfill the criteria established by Hagberg et al hereas three represent clinical variants. Detailed biochemical and neurodiagnostic assessment was conducted in all patients. Reduction in cerebrospinal biogenic amine metabolites and characteristic alterations in respiratory, sleep, and EEG patterns were helpful in supporting the clinical diagnosis in the fifteen patients with typical features of Rett syndrome. In the remaining three patients, the modalities were much less helpful in establishing the diagnosis. Until a molecular marker is defined, diagnosis must depend on careful clinical assessment.

Adolescent↗
PubMed1987

The inherited neurodegenerative disorders of childhood: clinical assessment.

This review represents an examination of four groups of neurodegenerative diseases, namely the sphingolipidoses, the adrenoleukodystrophy complex, the neuronal ceroid lipofuscinoses, and the sialidoses/sialuria complex. Using a combination of clinical assessment, neuroradiologic appearance, and clinical neurophysiology, one may develop strategies that lead to specific chemical or biochemical determinations for specific diagnoses. In general, disorders of white matter may be distinguished from disorders of gray matter by their appearance on computed tomography and by abnormalities of nerve conduction velocities and auditory brain stem responses. In contrast, disorders of gray matter may be distinguished from disorders of white matter by their appearance on computed tomography and utilization of electroretinography, visual evoked responses, and, to a lesser extent, EEG findings. Where necessary, skin, conjunctival, or nerve biopsy may prove to be useful adjuncts to the diagnosis. Presently, treatment depends on prevention, although aggressive efforts are under way to establish corrective therapy by enzyme replacement. To this end, the use of already existing animal models may prove to be helpful.

Adrenoleukodystrophy↗
PubMed1986

Krabbe disease: specific MRI and CT findings.

In three patients with Krabbe disease (galactosylceramide lipidosis), CT and MRI patterns progressed with the evolution of the disease. At first, discrete and symmetric dense areas on CT were found in deep gray matter of hemispheres and brainstem, and also in periventricular and capsular white matter. MRI showed decreased T1 values with normal or slightly decreased T2 values in those areas and large symmetric "plaque-like" lesions with high T1 and T2 values in white matter of the centrum semiovale. Later, both CT and MRI revealed diffuse reduction in gray matter and, more profoundly, in white matter mass. These findings may alert clinicians to the possibility of Krabbe disease in infants with progressive encephalopathy.

Atrophy↗