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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intellectual and cognitive function was studied in 43 patients (21 men and 22 women) with myotonic muscular dystrophy (MMD). The inheritance distribution was 18 paternal, 10 maternal, and 15 unknown. All patients received the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale, the Halstead-Reitan Neuropsychological Test Battery, and the Aphasia Screening Test. Significantly lower scores (p less than 0.05) were found on all intellectual and cognitive impairment tests in both men and women of the maternal inheritance MMD subgroup, compared with the paternal inheritance MMD subgroup and with the normative data. Scores for patients with paternally inherited disease did not differ significantly from normative data for verbal, performance, or full scale intelligence quotients and memory quotients. There were no significant differences in intellectual and cognitive test scores between men and women for the group as a whole, for the maternal inheritance subgroup, or for the paternal inheritance subgroup. It is suggested that inheritance pattern is a necessary variable in studies investigating intellectual and cognitive function in MMD. Although the reason for the association of lower intellectual and cognitive function in MMD of maternal inheritance is not known, the data presented here may be useful for genetic counseling.
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PMID:Intellectual and cognitive function in adults with myotonic muscular dystrophy. 370 14

The aim of the study was to evaluate whether children with merosin-positive or merosin-deficient congenital muscular dystrophy (CMD) show any cognitive impairment and whether this is related to brain abnormalities on magnetic resonance imaging (MRI). Twenty-two patients (age range: 5.8-15.3 years) were assessed by the Wechsler Intelligence Scales. Twelve were merosin-positive and ten merosin-deficient. One child had severe mental retardation and could not be tested. The full scale IQ in the remaining 21 ranged from 51 to 134, the verbal IQ ranged from 78 to 136 and the performance from 51 to 136. Of the twelve children with normal merosin one had a mild delay (IQ < 75) and two were borderline (IQ 75-95). Of the ten children with merosin-deficiency, one showed severe mental retardation and could not be tested, one showed a mild delay and two had borderline results. While the children with merosin deficiency with the typical diffuse white matter changes on MRI had normal scores, the children who in addition had cerebellar hypoplasia had lower performance IQ. The child with cortical dysplasia had severe mental retardation. Our results suggest that the spectrum of cognitive abilities in CMD is very wide even within genetically homogeneous conditions.
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PMID:Cognitive abilities in children with congenital muscular dystrophy: correlation with brain MRI and merosin status. 1054 41

Ten patients with myotonic muscular dystrophy (MD) were examined by auditory event-related potentials (P300 ERPs), spirometric and blood gas analyses: arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2) and arterial oxygen saturation (SaO2). The aim of the study was to analyse the frequency of ERP abnormalities in this disease and to determine whether the neurophysiological evidence of cognitive impairment might be related to the ventilatory function abnormalities frequently described in MD. The mean P300 latency was significantly altered in MD patients compared with controls; P300 latencies did not correlate with spirometric parameters, blood gas values or with age, age at onset, duration or clinical status of the disease. This study provides neurophysiological evidence of cognitive impairment in MD patients. The cognitive deficits are not related to alveolar hypoventilation and appear to be a non progressive feature of the disease.
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PMID:P300 and respiratory findings in myotonic muscular dystrophy. 1056 15

Several forms of inherited muscular dystrophy are associated with brain abnormalities and cognitive impairment. One of the most common and severe of these diseases is Duchenne muscular dystrophy (DMD). Dystrophin, the product of the DMD gene, is found in neurones, where it is associated with the postsynaptic membrane. Cognitive impairment in individuals with DMD is thought to be due to an abnormality in the neuronal membrane that is caused by lack of dystrophin. Recent experimental evidence has provided valuable clues in our understanding of the complex molecular neurobiology of muscular dystrophy.
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PMID:The neurobiology of duchenne muscular dystrophy: learning lessons from muscle? 1067 8

Twelve patients from 11 Israeli families with congenital muscular dystrophy were evaluated between 1991 and 2001. There were six males and six females, of whom six were merosin negative and six were merosin positive. Serum creatine kinase levels were highly elevated in the merosin-negative group. Four of the children were cognitively normal but nonambulant. Two had unusual clinical findings of severe cognitive and motor developmental dysfunction. Four infants in the merosin-positive group who had normal serum creatine kinase levels had early-onset severe motor weakness and died within the first year of life owing to ventilatory insufficiency. The other two were ambulant and had normal cognitive development and elevated serum creatine kinase levels. Noteworthy, two of the six children with merosin-negative congenital muscular dystrophy had cognitive impairment, and four of the six children with merosin-positive congenital muscular dystrophy had a severe form of the disease with ventilatory insufficiency and death during infancy.
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PMID:Congenital muscular dystrophy in Israeli families. 1215 May 78

Creatine monohydrate (CrM) supplementation may increase strength in some types of muscular dystrophy. A recent study in myotonic muscular dystrophy type 1 (DM1) did not find a significant treatment effect, but measurements of muscle phosphocreatine (PCr) were not performed. We completed a randomized, double-blind, cross-over trial using 34 genetically confirmed adult DM1 patients without significant cognitive impairment. Participants received CrM (5 g, approximately 0.074 g/kg daily) and a placebo for each 4-month phase with a 6-week wash-out. Spirometry, manual muscle testing, quantitative isometric strength testing of handgrip, foot dorsiflexion, and knee extension, handgrip and foot dorsiflexion endurance, functional tasks, activity of daily living scales, body composition (total, bone, and fat-free mass), serum creatine kinase activity, serum creatinine concentration and clearance, and liver function tests were completed before and after each intervention, and muscle PCr/beta-adenosine triphosphate (ATP) ratios of the forearm flexor muscles were completed at the end of each phase. CrM supplementation did not increase any of the outcome measurements except for plasma creatinine concentration (but not creatinine clearance). Thus, CrM supplementation at 5 g daily does not have any effects on muscle strength, body composition, or activities of daily living in patients with DM1, perhaps because of a failure of the supplementation to increase muscle PCr/beta-ATP content.
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PMID:Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1. 1469 98

Analyses of deletions in the dystrophin gene and of cognitive status were performed on patients with Duchenne (DMD) or Becker (BMD) muscular dystrophy in order to find a correlation between both features. Molecular study by multiplex and simplex PCR of dystrophin exons led to the identification of 51 deletions in 126 unrelated patients. Most of them were frameshift, in full agreement with severe clinical symptoms, three patients with a BMD-like phenotype had in-frame mutations. Deletions were localized with reference to the different dystrophin isoform sequences and were clustered in two main areas, 5' and central+ 3' end of the gene. Cognitive abilities were tested in 47 out of 51 patients with identified mutations, 23 of them being mentally impaired. Comparison of molecular and neuropsychological features showed that deletions localized in central and 3' parts of the gene (18 out of 23) are preferentially associated with mental impairment. Fourteen of them were found in the regulatory and coding sequences for the three CNS specific carboxy terminal isoforms. Therefore, though mutations with variable locations may lead to cognitive impairment, our results show that deletions in the distal portion of the gene are basically related to mental retardation.
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PMID:Dystrophin deletions and cognitive impairment in Duchenne/Becker muscular dystrophy. 1497 63

The Duchenne muscular dystrophy (DMD) is a muscular dystrophy with cognitive impairment present in 20-30% of the cases. In the present study, in order to study the relationship between the alpha-dystroglycan (alpha-DG) immunostaining in skeletal muscle and cognitive performance in DMD patients, 19 were assessed. Twelve patients performed the intelligence quotient (IQ) below the average. Among the 19 patients, two were assessed by the Stanford-Binet test and 17 by Wechsler Intelligence Scale for Children-III (WISC-III). Nine patients performed a verbal IQ below the average, only three patients performed an average verbal IQ. The muscle biopsies immunostained with antibodies to alpha-DG showed that 17 patients presented a low expression, below 25% of the total fibers. Two patients presented alpha-DG immunostaining above 40% and an IQ within the average. No significant statistical relationship was demonstrated among total IQ, verbal IQ and execution IQ and alpha-DG immunostaining at these patients muscle samples.
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PMID:Duchenne muscular dystrophy: alpha-dystroglycan immunoexpression in skeletal muscle and cognitive performance. 1640 Apr 17

Muscular dystrophy patients often show cognitive impairment, in addition to muscle degeneration caused by dystrophin gene defects. The cognitive impairments lead to speculation that the dystrophin protein family may play a key role at neuronal synapses. Dystrophin regulates the stability of selected GABA(A) receptor subtypes and alpha3-containing nicotinic acetylcholine receptors (nAChRs) at a subset of central GABAergic and peripheral sympathetic nicotinic neuron synapses. Similarly, utrophin, the autosomal homologue of dystrophin, is not required for clustering but indirectly stabilizes muscle-type nAChRs at the neuromuscular junction. We examined dystrophin and utrophin expression and localization in the avian parasympathetic ciliary ganglion (CG) to determine whether these proteins play a general role at neuronal nicotinic synapses. We have determined that full-length utrophin and dystrophin and the short dystrophin isoform Dp116 are the major isoforms expressed in the CG based on immunoblotting and immunolabeling. Unexpectedly, the cytoskeletal proteins were not detected at nicotinic synapses or in CG neurons. They are expressed in myelinating and non-myelinating Schwann cells. Further, utrophin expression developmentally precedes that of dystrophin. The proteins show partially overlapping distributions, but also differential accumulation along the surface membrane of Schwann cells adjacent to neuronal somata versus axonal processes. Our findings are consistent with reports that dystrophin protein family members function in the maintenance of cell-cell interactions and myelination by anchoring the Schwann cell surface membrane to the basal lamina. In contrast, our results differ from those in skeletal muscle and a subset of sympathetic neurons where utrophin and dystrophin localize at nicotinic synapses.
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PMID:Dystrophin and utrophin isoforms are expressed in glia, but not neurons, of the avian parasympathetic ciliary ganglion. 1853 35

While the function of dystrophin in muscle disease has been thoroughly investigated, dystrophin and associated proteins also have important roles in the central nervous system. Many patients with Duchenne and Becker muscular dystrophies (D/BMD) have cognitive impairment, learning disability, and an increased incidence of some neuropsychiatric disorders. Accordingly, dystrophin and members of the dystrophin-associated glycoprotein complex (DGC) are found in the brain where they participate in macromolecular assemblies that anchor receptors to specialized sites within the membrane. In neurons, dystrophin and the DGC participate in the postsynaptic clustering and stabilization of some inhibitory GABAergic synapses. During development, alpha-dystroglycan functions as an extracellular matrix receptor controlling, amongst other things, neuronal migration in the developing cortex and cerebellum. Several types of congenital muscular dystrophy caused by impaired alpha-dystroglycan glycosylation cause neuronal migration abnormalities and mental retardation. In glial cells, the DGC is involved in the organization of protein complexes that target water-channels to the plasma membrane. Finally, mutations in the gene encoding epsilon-sarcoglycan cause the neurogenic movement disorder, myoclonus-dystonia syndrome implicating epsilon-sarcoglycan in dopaminergic neurotransmission. In this review we describe the recent progress in defining the role of the DGC and associated proteins in the brain.
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PMID:The neurobiology of the dystrophin-associated glycoprotein complex. 1917 27


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