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Menachem Sadeh

Publications and source records attributed to Menachem Sadeh.

At least 19 recordsLinked to original sources
PubMed2006

A benign congenital myopathy in an inbred Samaritan family.

We describe a novel form of myopathy in a mother and her two daughters from an inbred Samaritan family. The patients displayed severe neonatal hypotonia, lethargy and dysmorphic features. Motor milestones were delayed; however, the hypotonia and muscle weakness gradually improved during the first 2 years of life and independent walking was achieved by 18 months. The mother at the age of 23 years shows myopathic facies and minimal proximal weakness. Her intelligence is normal. Her muscle biopsy revealed central nuclei and disruption of the intermyofibrillary network with moth eaten and spiral fibers. Mutations in SMN, MTM1 and the myotonic dystrophy genes were excluded. We suggest this is a new benign form of congenital myopathy. Inheritance is probably autosomal recessive.

Abnormalities, Multiple↗
PubMed2006

Low-level laser therapy applied transcranially to rats after induction of stroke significantly reduces long-term neurological deficits.

BACKGROUND AND PURPOSE: Low-level laser therapy (LLLT) modulates various biological processes. In the present study, we assessed the hypothesis that LLLT after induction of stroke may have a beneficial effect on ischemic brain tissue. METHODS: Two sets of experiments were performed. Stroke was induced in rats by (1) permanent occlusion of the middle cerebral artery through a craniotomy or (2) insertion of a filament. After induction of stroke, a battery of neurological and functional tests (neurological score, adhesive removal) was performed. Four and 24 hours poststroke, a Ga-As diode laser was used transcranially to illuminate the hemisphere contralateral to the stroke at a power density of 7.5 mW/cm2. RESULTS: In both models of stroke, LLLT significantly reduced neurological deficits when applied 24 hours poststroke. Application of the laser at 4 hours poststroke did not affect the neurological outcome of the stroke-induced rats as compared with controls. There was no statistically significant difference in the stroke lesion area between control and laser-irradiated rats. The number of newly formed neuronal cells, assessed by double immunoreactivity to bromodeoxyuridine and tubulin isotype III as well as migrating cells (doublecortin immunoactivity), was significantly elevated in the subventricular zone of the hemisphere ipsilateral to the induction of stroke when treated by LLLT. CONCLUSIONS: Our data suggest that a noninvasive intervention of LLLT issued 24 hours after acute stroke may provide a significant functional benefit with an underlying mechanism possibly being induction of neurogenesis.

Animals↗
PubMed2006

Prospective evaluation of malignant middle cerebral artery infarction with blood-brain barrier imaging using Tc-99m DTPA SPECT.

BACKGROUND: Malignant middle cerebral artery (MMCA) infarction is associated with severe brain edema which may lead to a rapid deterioration of consciousness, increase of intracranial pressure, brain midline shift and finally, herniation. We examined the correlation between the degree of the blood-brain barrier (BBB) permeability and MMCA. METHODS: Twenty-five consecutive patients (17 men and 8 women, mean age 62.1+/-10.1) were included in the study. Each patient had a daily clinical examination, and the neurological deficits were scored using NIHSS score. A CT without contrast material was performed in all patients. (99m)Tc-DTPA SPECT was performed at 36 h after the stroke. A quantitative index of BBB breakdown (disruption index) was calculated. RESULTS: The mean volume of stroke was 138+/-87 cm(3). The mean DTPA disruption index was 6.6+/-4.6 (range 1.0-21.0). The mean NIHSS score was 14+/-4 (p=0.2). Five of 25 patients had brain herniation as evidenced on brain CT. The volume of stroke was only marginally elevated in patients with herniation (p=0.062). All patients showed significant, inverse correlation between NIHSS score and DTPA uptake (r=-0.43, p=0.033). There was a significant correlation between the extent of DTPA distribution (more than one vascular territory) and the occurrence of herniation (p<0.001). CONCLUSIONS: DTPA-SPECT imaging is a reliable complementary predictive tool in patients with an MCA stroke. The specific pattern found on DTPA SPECT, compatible with diffuse BBB disruption, may be of value in predicting "malignant MCA."

Aged↗
PubMed2006

Eosinophilia, myositis, and myasthenia gravis associated with a thymoma.

Hypereosinophilia has been associated with a wide variety of systemic disorders, including myositis. Myositis develops in a minority of patients with myasthenia gravis associated with a thymoma. We present a patient who developed a life-threatening myopathy in which testing demonstrated the concurrence of hypereosinophilia, myositis, and myasthenia gravis associated with thymoma. Thymoma-associated T-cell abnormalities may well have contributed to this rare association. This case underscores the need to reevaluate constantly the presumed cause of clinical complaints, as more than one cause may be present.

Aged↗
PubMed2006

Visual spatial neglect in multiple sclerosis.

Neuropsychological dysfunction in multiple sclerosis (MS) patients is now a well-established clinical finding. We examined the entity of visual spatial neglect in demyelinating disease and its correlation to the functional and neuroradiological parameters. The phenomenon of visual spatial neglect was examined in 20 (5 male and 15 female) MS patients. Two different examination methods were used--the line bisection test and the random shape cancellation test. The results were compared with 20 aged matched control individuals. The correlation of the visual spatial neglects to neurological deficits and handicaps, using Kurtzke's Expanded Disability Status Scale (EDSS), as well as with the MRI's neuroradiological findings, was analyzed. A highly significant different result on the line bisection test for three various line lengths (p = .006, p < .0001, p < .001) with displacement towards the right side was found. In all the cancellation subtests, a significant difference in error rate was found in comparing patients to controls toward a higher one on the left side of the MS patients (p = .005, p < .002, p < .0001 and p = .02 in the left side subtest, and p = n.s. in the right side subtest). There was no significant correlation between the cancellation tests and bisection results and the EDSS scale data, as well as with the neuroradiological findings. The present results demonstrate the presence of visual spatial neglect among MS patients, even without the demonstration of a characteristic neuroanatomical lesion. The hypotheses for this finding are discussed with a stress on the possibility of disruption of multiple intrahemispheric connections, especially under the condition of asymmetry of dominance regarding spatial attention.

Adult↗
PubMed2006

Acute steroid responsive small-fiber sensory neuropathy: a new entity?

Small-fiber neuropathy is often idiopathic and commonly follows a chronic course. Treatment is often effective in treating the core symptom of pain, but it has no effect on the pathologic process. We describe four patients with acute small-fiber neuropathy who responded dramatically to steroid therapy. All patients had acute onset neuropathic pain, normal nerve conduction studies, and evidence of small-fiber dysfunction in quantitative sensory testing and skin biopsy. Symptoms were distal and symmetrical in three patients and generalized in one patient. In two cases, the neuropathy presented as an erythromelalgia-like syndrome. Marked clinical improvement occurred 1-2 weeks after oral prednisone therapy was initiated. Three patients remained symptom free, and one patient experienced recurrence of neuropathy after prednisone was tapered.

Adolescent↗
PubMed2006

Asymptomatic or minimally symptomatic hyperCKemia: histopathologic correlates.

BACKGROUND: Persistent creatine kinase elevation is occasionally encountered in subjects without any clinical manifestation of a neuromuscular disorder or any condition known to be associated with increased serum CK levels. It is still unresolved whether extensive investigations and specifically a muscle biopsy should be performed in clinically normal individuals with elevated CK levels. OBJECTIVE: To study the muscle pathology of patients with asymptomatic or minimally symptomatic hyperCKemia. METHODS: The clinical and laboratory data of patients with persistent hyperCKemia and normal neurologic examination were reviewed and their muscle biopsies evaluated. RESULTS: The study group included 40 patients aged 7-67 years; the male to female ratio was 3:1. Nineteen patients were completely asymptomatic, 20 had mild non-specific myalgia, and 1 had muscle cramps. Electromyography was performed in 27 patients and showed myopathic changes in 7 (26%). Abnormal muscle biopsy findings (e.g., increased variation in fiber size, increased number of central nuclei, and occasional degenerating fibers) were detected in 22 of the 40 patients (55%). No fat or glycogen accumulation was detected. Immunohistochemistry demonstrated abnormal dystrophin staining in 3 patients (8%), resembling the pathologic changes of Becker muscular dystrophy. No abnormal findings were detected on immunohistochemical staining for merosin, dysferlin, caveolin 3, or alpha and gamma sarcoglycans. The EMG findings did not correlate with the pathologic findings. CONCLUSIONS: Abnormal muscle biopsies were found in 55% of patients with asymptomatic or minimally symptomatic hyperCKemia. Specific diagnosis of muscular dystrophy, however, was possible in only 8% of the patients.

Adolescent↗
PubMed2005

Extended phenotype in the transthyretin Tyr77 familial amyloid polyneuropathy.

The transthyretin Tyr77 variant of familial amyloid polyneuropathy (FAP) has been identified in a few North American and European patients, but the full spectrum of its clinical manifestations is still not known. We report a 3-generation family of Jewish-Yemenite origin with Tyr77 FAP presenting with atypical features. The affected individuals had sensorimotor and autonomic neuropathy and cardiomyopathy accompanied by prominent dysphagia, hearing loss and asymptomatic carpal tunnel syndrome. Brain MRI in the proband showed multifocal white matter lesions. These features extend the reported Tyr77 phenotype and support the modifying effect of additional factors on the disease expression.

Amyloid Neuropathies, Familial↗
PubMed2005

No overall hyposialylation in hereditary inclusion body myopathy myoblasts carrying the homozygous M712T GNE mutation.

Hereditary inclusion body myopathy (HIBM) is a unique group of neuromuscular disorders characterized by adult-onset, slowly progressive distal and proximal muscle weakness, which is caused by mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), the key enzyme in the biosynthetic pathway of sialic acid. In order to investigate the consequences of the mutated GNE enzyme in muscle cells, we have established cell cultures from muscle biopsies carrying either kinase or epimerase mutations. While all myoblasts carrying a mutated GNE gene show a reduction in their epimerase activity, only the cells derived from the patient carrying a homozygous epimerase mutation present also a significant reduction in the overall membrane bound sialic acid. These results indicate that although mutations in each of the two GNE domains result in an impaired enzymatic activity and the same HIBM phenotype, they do not equally affect the overall sialylation of muscle cells. This lack of correlation suggests that the pathological mechanism of the disease may not be linked solely to the well-characterized sialic acid pathway.

Cell Membrane↗
PubMed2005

Early clinical heterogeneity in choreoacanthocytosis.

BACKGROUND: Choreoacanthocytosis (CHAC) is a slowly progressive multisystem disorder with involuntary movements, cognitive decline, behavioral changes, seizures, and polyneuropathy caused by mutations in the VPS13A gene. OBJECTIVE: To describe the early clinical features and possible genotype-phenotype correlation in CHAC. DESIGN AND SETTING: Case series in a tertiary care center. PATIENTS AND MAIN OUTCOME METHODS: Choreoacanthocytosis was diagnosed in 3 patients of Jewish origin from 3 unrelated families. We reviewed their medical histories and performed molecular analysis by screening all 73 exons of VPS13A. RESULTS: Trichotillomania, hypertrophic cardiomyopathy, and idiopathic hyperCKemia, in 1 patient each, preceded the development of the full clinical spectrum of CHAC by 2 to 20 years. At diagnosis, 2 patients manifested signs of overt neuromuscular involvement and were homozygous for the 6059delC mutation, whereas 1 patient had only hyporeflexia and was homozygous for the EX23del mutation. Because only 1 of the 2 patients with 6059delC had cardiomyopathy, its relevance to CHAC is unclear. CONCLUSIONS: These findings extend the knowledge of significant early clinical heterogeneity in CHAC and suggest a possible genotype-phenotype correlation. Awareness of the early manifestations may prevent misdiagnosis and enable appropriate genetic counseling.

Adult↗
PubMed2005

Auditory hallucinations in acute stroke.

Auditory hallucinations are uncommon phenomena which can be directly caused by acute stroke, mostly described after lesions of the brain stem, very rarely reported after cortical strokes. The purpose of this study is to determine the frequency of this phenomenon. In a cross sectional study, 641 stroke patients were followed in the period between 1996-2000. Each patient underwent comprehensive investigation and follow-up. Four patients were found to have post cortical stroke auditory hallucinations. All of them occurred after an ischemic lesion of the right temporal lobe. After no more than four months, all patients were symptom-free and without therapy. The fact the auditory hallucinations may be of cortical origin must be taken into consideration in the treatment of stroke patients. The phenomenon may be completely reversible after a couple of months.

Acute Disease↗
PubMed2004

The homozygous M712T mutation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase results in reduced enzyme activities but not in altered overall cellular sialylation in hereditary inclusion body myopathy.

Hereditary inclusion body myopathy (HIBM) is a neuromuscular disorder, caused by mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, the key enzyme of sialic acid biosynthesis. In Middle Eastern patients a single homozygous mutation occurs, converting methionine-712 to threonine. Recombinant expression of the mutated enzyme revealed slightly reduced N-acetylmannosamine kinase activity, in agreement with the localization of the mutation within the kinase domain. B lymphoblastoid cell lines derived from patients expressing the mutated enzyme also display reduced UDP-N-acetylglucosamine 2-epimerase activity. Nevertheless, no reduced cellular sialylation was found in those cells by colorimetric assays and lectin analysis, indicating that HIBM is not directly caused by an altered overall expression of sialic acids.

Amino Acid Substitution↗
PubMed2004

Apparent weakness of ulnar-innervated muscles in radial palsy.

Muscle strength was assessed in 11 patients with radial or posterior interosseus palsy. Apparent weakness was found in the dorsal and palmar interossei and the abductor digiti minimi. These muscles insert on the extensor expansions, and their activation is associated with concomitant contraction of finger flexors and extensors. This apparent weakness may be due to their unopposed traction on the extensor expansion by the paralyzed extensor digitorum.

Adult↗
PubMed2004

Pathological laughter as a symptom of midbrain infarction.

Pathological laughter is an uncommon symptom usually caused by bilateral, diffuse cerebral lesions. It has rarely been reported in association with isolated cerebral lesions. Midbrain involvement causing pathological laughter is extremely unusual. We describe three patients who developed pathological laughter after midbrain and pontine-midbrain infarction. In two patients a small infarction in the left paramedian midbrain was detected, whereas the third one sustained a massive bilateral pontine infarction extending to the midbrain. Laughter heralded stroke by one day in one patient and occurred as a delayed phenomenon three months after stroke in another. Pathological laughter ceased within a few days in two patients and was still present at a two year follow-up in the patient with delayed-onset laughter. Pathological laughter can herald midbrain infarction or follow stroke either shortly after onset of symptoms or as a delayed phenomenon. Furthermore, small unilateral midbrain infarctions can cause this rare complication.

Brain Stem Infarctions↗
PubMed2003

E-box mutations in the RAPSN promoter region in eight cases with congenital myasthenic syndrome.

Myogenic determination factors are basic helix-loop-helix proteins that govern specification and differentiation of muscle cells, and bind to the E-box consensus sequence CANNTG in promoter regions of muscle-specific genes. No E-box mutation has been reported to date. RAPSN encodes rapsyn, a 43 kDa postsynaptic peripheral membrane protein that clusters the nicotinic acetylcholine receptor at the motor endplate. Transcriptional regulation mechanisms of RAPSN have not been studied. We here report two novel E-box mutations in the RAPSN promoter region in eight congenital myasthenic syndrome patients. Patient 1 carries -27C-->G that changes an E-box at -27 to -22 from CAGCTG to GAGCTG. An allele harboring -27C-->G is not transcribed in patient's muscle. Patients 2-8 are of Oriental Jewish stock of Iraqi or Iranian origin with facial malformations, and harbor -38A-->G that changes another E-box at -40 to -35 from CAACTG to CAGCTG, which does not affect the consensus CANNTG sequence. Haplotype analysis shows that -38A-->G arises from a common founder. For each mutation, position +1 represents the major transcriptional start site that we determine to be 172 nucleotides upstream of the translational start site. Electrophoretic mobility shift assays reveal that -38A-->G gains, and -27C-->G looses, binding affinity for different components of nuclear extracts of C2C12 myotubes. Luciferase reporter assays show that both -38A-->G and -27C-->G attenuate reporter gene expression in C2C12 myotubes, and that -27C-->G additionally attenuates reporter gene expression in MyoD- or myogenin-transfected HEK cells. The -27C-->G mutation also markedly attenuates the enhancer activity of an E-box on an SV40 promoter. Impaired transcriptional activities of the RAPSN promoter region predict reduced rapsyn expression and endplate acetylcholine receptor deficiency.

Adolescent↗
PubMed2003

Mutations spectrum of GNE in hereditary inclusion body myopathy sparing the quadriceps.

Hereditary Inclusion Body Myopathy (HIBM) is a unique group of neuromuscular disorders characterized by adult onset and a typical muscle pathology. We have recently identified the gene encoding for a bifunctional enzyme, UDP-N-acetylglucosamine 2 epimerase/N-acetylmannosamine kinase (GNE), as the mutated gene in the prototype form of the disease presenting quadriceps sparing, particularly common in Middle Eastern Jews. Interestingly, we have identified the homozygous M712T Middle Eastern Jewish mutation also in two unrelated Middle Eastern Moslem families. We have also evaluated the involvement of GNE in several families from worldwide non-Jewish ethnic origins presenting symptoms similar to the Middle Eastern HIBM prototype. A total of 14 GNE mutations were identified (one nonsense and 13 missense), of which six are novel: an homozygous missense mutation in a consanguineous family from Italy and in a non consanguineous family from USA, and distinct compound heterozygotes in families from Germany, Italy, Ireland, Bahamas, USA and East India. This study brings to 17 the number of reported GNE mutations in quadriceps sparing myopathy, occurring either in the epimerase or the kinase domain of the enzyme. The mechanism leading to this unique phenotype still remains to be elucidated.

Adolescent↗
PubMed2003

Muscle glycogen depletion and increased oxidative phosphorylation following status epilepticus.

We describe complete glycogen depletion and increased respiratory chain enzyme activity in a muscle biopsy obtained prior to the demise of a patient in multiorgan failure following status epilepticus. These findings validate the theoretical basis of muscle energy turnover during status epilepticus: the increased demand for energy leads to complete depletion of glycogen reserves. The attempt to preserve adenosine triphosphate requirements results in increased activity of respiratory chain enzymes.

Biopsy↗