Sarcolemmal deficiency of sarcoglycan complex in an 18-month-old Turkish boy with a large deletion in the beta sarcoglycan gene.

Limb-girdle muscular dystrophy type 2E (LGMD-2E) is caused by autosomal recessive defects in the beta sarcoglycan (SGCB) gene located on chromosome 4q12. In this case report, the clinical findings, histopathological features and molecular genetic data in a boy with ß sarcoglycanopathy are presented. An 18-month-old boy had a very high serum creatinine phosphokinase (CPK) level that was accidentally determined. The results of molecular analyses for the dystrophin gene was found to be normal. He underwent a muscle biopsy which showed dystrophic features. Immunohistochemistry showed that there was a total loss of sarcolemmal sarcoglycan complex. DNA analysis revealed a large homozygous deletion in the SCGB gene. During 4 years of follow-up, there was no evidence to predict a severe clinical course except the muscle enzyme elevation and myopathic electromyography (EMG) finding. The presented milder phenotype of LGMD-2E with a large deletion in the SGCB gene provided additional support for the clinical heterogeneity and pathogenic complexity of the disease.

Identification of axonal involvement in Hallervorden-Spatz disease with magnetic resonance spectroscopy.

Hallervorden-Spatz disease is a neurodegenerative disorder associated with cysteine-iron complex accumulation typically seen as bilateral symmetrical hypointense signal changes in the medial globus pallidus on magnetic resonance imaging. We used magnetic resonance spectroscopy to identify and quantify neuronal damage in two siblings with Hallervorden-Spatz disease. The first patient presenting with a rapidly progressive extrapyramidal syndrome had markedly decreased N-acetylaspartate (NAA) to creatinine (Cr) ratios in the globus pallidi and the periatrial white matter. He also had increased myoinositol (mI) to creatinine (Cr) ratios implying glial proliferation in the affected regions. However the second patient who had the initial presentation of disease had normal NAA/Cr and mI/Cr ratios. These findings indicate that the quantification of NAA:Cr and mI:Cr ratios might be used to predict the extent of neuronal axonal loss and glial proliferation in patients with Hallervorden-Spatz disease respectively.

Proinflammatory cytokines, prostaglandins and zinc in febrile convulsions.

BACKGROUND: Some changes in the levels of proinflammatory cytokines, prostaglandins and zinc (Zn) in peripheral blood and cerebrospinal fluid (CSF) have been suggested to occur for the pathogenesis of febrile convulsions (FC). METHODS: In order to test this hypothesis, the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta and prostaglandins (PGE(2), PGF(2 alpha), PGD(2)) in the CSF and plasma and the levels of Zn in serum and CSF were investigated in children during the acute and late phases of FC. Results were compared with control subjects with meningismus. RESULTS: During the acute phase of FC, children had significantly elevated plasma levels of IL-1 beta, CSF levels of TNF-alpha, plasma levels of PGE(2), PGF(2 alpha) and PGD(2) and CSF levels of PGD(2) (P<0.05). A positive correlation between the degree of fever and plasma IL-1 beta levels was observed in both patients and controls. Three months after the acute phase of FC, plasma levels of IL-1 beta had returned to levels seen in controls. Children with FC also had significantly decreased serum Zn levels during the acute phase (P<0.05). However, there was no significant difference between the groups with respect to CSF Zn levels (P>0.05). CONCLUSIONS: During the acute phase of FC, patients had significantly increased plasma IL-1 beta and prostaglandin levels and decreased serum Zn levels. These changes may be responsible for FC pathogenesis.

Lymphocyte subsets and inflammatory mediators in patients with subacute sclerosing panencephalitis.

A defective cell-mediated immunity and inflammatory cytokines are suggested in the pathogenesis of subacute sclerosing panencephalitis. In this study we analyzed lymphocyte subsets in peripheral blood and concentrations of interleukin-1alpha (IL-1alpha), interleukin-2 (IL-2alpha), tumor necrosis factor-alpha (TNF-alpha), and platelet activating factor in plasma and cerebrospinal fluid before and after immunomodulatory therapy (interferon-alpha plus isoprinosine) in three patients with subacute sclerosing panencephalitis. Increased percentage of CD8+cells (T-suppressor/cytotoxic cell) and CD16+CD56+cells (NK cell) and reduced percentage of CD3+/HLA-DR+ (active T-cell) and CD3+ (total T-cell) cells were found before therapy. After immunomodulatory therapy, CD3+/HLA-DR+ (active T-cell) cells were markedly increased and there was a slight increase in the percentages of all lymphocyte subsets in the patients. The concentrations of platelet activating factor in plasma and cerebrospinal fluid were higher than the mean value in controls. Cerebrospinal fluid and plasma TNF-alpha and IL-2 levels were nondetectable in two patients who had a stationary course of disease and were markedly elevated in patient 3, who displayed a rapidly progressive course.

Pro-inflammatory cytokines, lymphocyte subsets and intravenous immunoglobulin therapy in Guillain-Barré syndrome.

Both cell-mediated immunity and humoral factors are involved in the pathogenesis of Guillain-Barré syndrome (GBS). Intravenous immunoglobulin (IVIG) has been reported to be a practical, effective and safe treatment in childhood GBS, although the mode of action of IVIG remains uncertain. We studied pro-inflammatory cytokines (interleukin-2, interleukin-1 alpha and tumor necrosis factor-alpha) in plasma and cerebrospinal fluid (CSF) and lymphocyte subsets in peripheral blood both in the acute phase and in the recovery period in six children with GBS treated with IVIG. Flow cytometry was used to determine the subsets of lymphocytes in peripheral blood, and cytokines analyses were performed by using ELISA technique. Results were compared with a control group of 20 healthy children. A standard protocol of IVIG (400 mg/kg/day for 5 days) was administered to all the patients. Plasma interleukin-2 concentrations and the number of HLA DR+ active T cells in peripheral blood were significantly higher in the acute phase of the disease than in the recovery period and in healthy controls. There was no significant difference in the other cytokine concentrations in plasma and CSF or in the other lymphocyte subsets in peripheral blood. Our data indicate that IVIG may provide its possible therapeutic effect by acting in the cell-mediated immunity in GBS patients.

Akinetic mutism due to diphenylhydantoin toxicity.

Akinetic mutism (AM) is a rare, specific, unconscious state. An AM patient seems to be awake, lacks mental activity, is unable to speak, and does not respond to any environmental stimulus. Cyclical sleep and awake states are maintained, and incontinence is present. Various factors such as tumor, vascular events, drug use and radiotherapy are responsible for the development of AM. A 12-year-old epileptic patient displayed AM and diphenylhydantoin toxicity (DPH). She seemed awake, was unable to speak or to understand, and had no movements with either spontaneous or noxious stimuli. Her serum DPH level was greater than 40 micrograms/ml. Magnetic resonance imaging (MRI) showed mild cerebellar atrophy. All known causes of AM were excluded. The AM state in this patient was considered to be due to toxic DPH levels. She regained her motor and mental activity within two months after carbamazepine was administered to replace DPH. She was symptom-free when examined at the two-year follow-up. No similar adverse effect of DPH has been reported to date.

Infantile polymyositis with normal serum creatine kinase level.

A 30-month-old boy who has been suffering progressive proximal muscle weakness and severe atrophy in shoulder and hip muscles from 11 months of age had prominent perivascular inflammatory cellular infiltration in his muscle biopsy and myopathic EMG changes. But his serum creatine kinase (CK) levels were repeatedly found to be within normal ranges. Oral prednisolone therapy (2 mg/kg/d) brought a complete recovery of muscle power and normalization of EMG and muscle biopsy findings. This report provides an additional support that the cases of infantile polymyositis with normal serum CK levels may respond well to steroid therapy.