A new form of childhood onset, autosomal recessive spinocerebellar ataxia and epilepsy is localized at 16q21-q23.

Childhood ataxias are a complex set of inherited disorders. Ataxias associated with generalized tonic-clonic epilepsy are usually included with the progressive myoclonus epilepsies (PME). Five disease entities, Unverricht-Lundborg disease, Lafora's disease, neuronal ceroid lipofuscinoses, myoclonic epilepsy with ragged red fibres and sialidoses, account for the majority of PME cases. Two rare forms of ataxia plus epilepsy, sensory ataxic neuropathy, dysarthria and ophthalmoparesis, and infantile onset spinocerebellar ataxia were described recently and found to be caused by defective mitochondrial proteins. We report here a large consanguineous family from Saudi Arabia with four affected children presenting with generalized tonic-clonic epilepsy, ataxia and mental retardation, but neither myoclonus nor mental deterioration. MRI and muscle biopsy of one patient revealed, respectively, posterior white matter hyperintensities and vacuolization of the sarcotubular system. We localized the defective gene by homozygosity mapping to a 19 Mb interval in 16q21-q23 between markers D16S3091 and D16S3050. Linkage studies in this region will allow testing for homogeneity of this novel ataxia-epilepsy entity.

Autosomal recessive hereditary neuropathy with focally folded myelin sheaths and linked to chromosome 11q23: a distinct and homogeneous entity.

We describe a six generation Saudi kindred, with a recessive hereditary motor and sensory neuropathy (HMSN). Four individuals were affected including two children (a boy and a girl) and a 23-year-old man. The fourth (a female) died at the age of 14 years. Onset of the disease was early (< 2 years) and the clinical and neurophysiological features were, generally, quite similar to those of an Italian family linked to chromosome 11q23. The peculiar pathologic pattern was irregular and redundant loops associated with folding of the myelin sheaths. The genetic study confirmed linkage to chromosome 11q23 and refined the location of the gene between D11S1311 and D11S917, a 3.3 cM region. These findings support the existence of a homogeneous and distinct entity within the form of HMSN associated with focally folded myelin sheaths.

Morphologic patterns of male infertility in Saudi patients. A University Hospital experience.

OBJECTIVE: To determine the predominant histopathological patterns seen in the testicular biopsies taken during the investigation of male infertility and to compare the obtained histopathological findings with those seen in other similar studies. METHODS: This is a retrospective study performed on 230 testicular biopsies which were examined in the Department of Pathology at King Khalid University Hospital in Riyadh over a period of 10 years. The histopathological findings were grouped into 8 different morphologic categories. We have utilized a classification that is principally morphologic but that uses known or suspected clinical associations in the case of karyotypic abnormalities and excurrent duct obstruction. RESULTS: Of the total of 230 testicular biopsies studied, 72 cases showed normal spermatogenesis, of which 50 cases were suspected to be associated with excurrent duct obstruction. Germinal cell aplasia with and without focal spermatogenesis was found in about 90 cases. Thirty cases showed hypospermatogenesis, 25 cases showed maturation arrest and 12 cases showed end stage tubular sclerosis with interstitial fibrosis. Only one case was noted to show features associated with karyotypic abnormalities. CONCLUSIONS: A higher percentage of germinal cell aplasia was noted in this study when compared with other similar investigations including one previous local study. Possible causes of these discrepancies may be related to several factors including environmental effects. The design of the different studies and the criteria used for patient selection or both could also explain the cause of these observed differences.

Prevalence of intratubular germ cell neoplasia of the testis.

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A novel form of familial congenital muscular dystrophy in two adolescents.

We report on two brothers (the product of first-degree consanguineous marriage; aged 15 and 12 years) who presented with severe hypotonia at birth, proximal muscle weakness associated with delayed motor milestones but normal cognitive function. Investigations (at 4 years of age) revealed mildly elevated serum creatine kinase (CK) levels (300 and 824 IU/l; N < or = 210). Muscle biopsies showed minimal change myopathy, no neurogenic atrophy but remarkable type-1 fibre predominance (up to 85.5%) without fibre-type disproportion. Clinical examination at 12 and 9 years, respectively, showed mild facial weakness and high-arched palate in both patients. The younger sibling also had ptosis but otherwise normal external ocular muscles. They showed symmetric proximal muscle weakness and wasting associated with calf-muscle hypertrophy. They could walk independently. A repeat muscle biopsy showed advanced dystrophic changes in the younger patient at the age of 10 years. Virtually all the remaining fibres were type 1. Immunohistochemistry revealed normal expression of the dystrophin-glycoprotein complex (DGC), including dystrophin, beta-dystroglycan, alpha-(adhalin), beta-, gamma-, and delta-sarcoglycan, laminin-alpha2 chain (merosin) and syntrophin. Mild dystrophic features and type-1 fibre predominance (92.5%) were seen in the biopsy of the older patient, whereas immunohistochemistry showed normal expression of the DGC. Both cases also showed clear expression of integrin alpha7 at the muscle fibre surface and in the blood vessels. Three years later, they could still walk, but with difficulty, and the older brother showed enlargement of the tongue and echocardiographic features of left ventricular dilated cardiomyopathy.

Intraventricular and leptomeningeal dissemination of a pilocytic cerebellar astrocytoma in a child with a ventriculoperitoneal shunt: case report.

Dissemination of a pilocytic cerebellar astrocytoma is a very rare occurrence. So far only eight cases have been reported in the literature and in only one of these cases had the tumour spread into the ventricles. We report a case of a child who presented with communicating hydrocephalus and a small cerebellar lesion. The patient was initially treated by a ventriculoperitoneal (VP) shunt and the lesion was followed-up. Two years later, intraventricular and leptomeningeal dissemination of the tumour which proved to be a pilocytic astrocytoma was documented. The role of the VP shunt in diverting metastasizing tumour cells into the ventricles is discussed.

Intramedullary ossified cavernous angioma of the spinal cord: case report.

A case of a heavily ossified cavernous angioma of the spinal cord along with its histological features and surgical implications is reported. The unusually dense calcification and even bone formation along with the unique eggshell-like cyst formation posed problems in diagnosis and surgical excision. This calcified vascular lesion was treated by subtotal excision.

Axonal dystrophy presenting as the megacystis-microcolon-intestinal hypoperistalsis syndrome.

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a neonatal intestinal syndrome, characterized by defective peristalsis and bladder dilatation, refractory to pharmacological treatment. Examinations of bowel and bladder have failed to demonstrate a pathological explanation for this syndrome. We describe a 7-month-old female infant with MMIHS who had generalized axonal dystrophy of her central, peripheral, and autonomic nervous systems, which may provide a neuropathological explanation for some cases of MMIHS.

Spectroscopic imaging of stroke in humans: histopathology correlates of spectral changes.

Previous studies of human stroke by 1H nuclear magnetic resonance spectroscopy have shown elevation of lactate lasting 3 to 6 months. Complete metabolic turnover of the elevated lactate pool has been demonstrated 5 weeks after a stroke. Its cellular localization is among the first questions requiring clarification. Information pertinent to this question came to us from a patient with a 2-week-old stroke by 1H nuclear magnetic resonance spectroscopic imaging 1 week before his death led to neuropathologic examination of the brain. 1H spectra from voxels including the infarcts showed increased lactate and decreased N-acetylaspartate. Histopathology showed sheets of foamy macrophages in the infarct, but few neurons. Macrophage density ranged from 196 cells/mm2 near the surface of the infarct to 788 near its medial margin. Glial density was 500 to 800 cells/mm2. Lactate concentration in voxels including portions of the infarct was estimated at 7 to 14 mM. Voxels showing low N-acetylaspartate and high lactate on spectroscopic imaging were associated with histopathologic sections containing foamy macrophages. Brain macrophages--which begin to appear 3 days after infarction and gradually disappear over several months--could be a major source of elevated lactate signals that persist for months after stroke.

Dysplasia of the corpus callosum in identical twins with nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (NKH) is an autosomal recessively inherited disorder of the glycine degradation pathway leading to accumulation of glycine in body fluids and tissues. Identical twins with nonketotic hyperglycinemia and dysplasia of the corpus callosum are described in support of the hypothesis that some patients with NKH have a genetic defect of the glycine degradation pathway resulting in abnormal corpus callosal development. It is important to screen for metabolic defects whenever similar structural defects are present.