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.

Two cases of Guillain-Barré syndrome during measles elimination campaign in Izmir.

The authors report two cases of Guillain-Barré Syndrome (GBS) occurred during a national measles vaccination campaign in Izmir, Turkey. Among more than 325,000 vaccine recipients, only 2 cases of GBS were observed within the 10-week risk period. These cases yielded an incidence of 0.615 per 100,000 vaccine doses. The authors think that association between measles vaccination and GBS is coincidental, rather than causal. However, an epidemiological evaluation in Turkey is needed to clearly show that there is no causal association between measles vaccination and GBS.

Subclinical neurological abnormalities in children with celiac disease receiving a gluten-free diet.

OBJECTIVES: Because clinically evident manifestations are frequent in adults with celiac disease (CD), we aimed to investigate whether early neurological abnormalities may be detected in children with CD. METHODS: Electroencephalography, electromyography, and somatosensory evoked potentials were performed in children with CD receiving a gluten-free diet. RESULTS: The neurophysiological tests revealed subclinical neurological abnormalities associated with CD in 3 (11%) of 27 children: 2 had peripheral polyneuropathy documented with electromyography, and 1 had prolonged latencies in somatosensory evoked potential. Magnetic resonance imaging showed abnormalities in 2 (7.4%) of children: pontine demyelinization in 1 and cortical atrophy in the other. CONCLUSIONS: Because the rate of neurological problems is increased in children with CD, neurological abnormalities should be carefully investigated early after the diagnosis of CD is made.

A new case of Martsolf syndrome.

Martsolf syndrome is an autosomal recessive syndrome characterized by microcephaly, mental retardation, cataract, hypogonadism and short stature. A seven-year-old boy was admitted to the hospital with growth retardation and difficulties in walking. His parents were first cousins. Bilateral lens extraction was performed during infancy because of congenital cataract. On physical examination he had short stature, microcephaly, micropthalmia, hypogonadism, mental retardation. Brain magnetic resonance imaging revealed alterations in the white matter. Up to date very few cases with this syndrome have been reported. This is the first case described in the Turkish population and may add valuable information to the literature.

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.

Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome) in a Turkish child.

We report a Turkish boy with PEHO syndrome (progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy). He had generalized hypotonia and abnormal eye movements during early infancy. Infantile spasms were seen in the second year of life. Arrest of psychomotor development and blindness were noticed early in childhood. Serial magnetic resonance imaging revealed progressive infratentorial atrophy with association of cortical atrophy and corpus callosum hypoplasia. This is an additional case of PEHO syndrome, to our knowledge the first such case from Turkey.

A case of Lafora's disease associated with cardiac arrhythmia.

Progressive myoclonic epilepsies are rare, genetically transmitted diseases characterized by epileptic seizures, myoclonus, and progressive neurologic deterioration. Unverricht-Lundborg disease, Lafora's disease, neuronal ceroid lipofuscinosis, mitochondrial disorders, and sialidosis are included in this group. Lafora's disease is a progressive disorder of the central nervous system with onset in the late first or second decade of life and is inherited in an autosomal-recessive pattern. The first clinical manifestation is generalized tonic-clonic seizures, myoclonus, or both, usually seen between the ages of 11 and 18 years. The other clinical manifestations are progressive dementia and limb ataxia. Diagnosis is based on showing the typical inclusions in the brain, liver, skin, or muscle tissue specimens. The case of a 6-year-old male patient, who was admitted with the clinical findings of third-degree atrioventricular block and dementia and eventually diagnosed with Lafora's disease, is presented.

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.

Infantile spasm: the effect of corticotropin (ACTH) on the free amino acid profile in cerebrospinal fluid.

Increased excitatory amino acid neurotransmission has been implicated in the pathogenesis of infantile spasm. In this study we studied the profile of free amino acids in cerebrospinal fluid (CSF) from 16 patients with infantile spasm before corticotropin (ACTH) treatment. After 10 weeks ACTH therapy the profile of amino acids in CSF was studied once more in eight of the patients. Eleven patients were in the symptomatic group, and five in the cryptogenic group. Increased aspartate levels were measured in CSF following ACTH therapy (P<0.05). It was concluded that aspartate might have an important role in hypothalamic-hypophyseal axis in patients with infantile spasm.

Associated brain abnormalities in patients with corpus callosum anomalies.

Forty-nine patients with corpus callosum (CC) anomalies were evaluated in terms of the clinical features and magnetic resonance imaging (MRI) findings. CC anomalies were classified as CC agenesis: 6 (12%), CC hypogenesis: 5 (10%), and CC hypoplasia: 38 (78%). In the CC hypoplasia group the mean value of the genu thickness of the CC was 0.29 +/- 0.1 cm, which was less than the normal value of the age-matched normal children (normal range: 0.6-1.2 cm). The associated brain abnormalities were in five distinct groups: gray matter abnormalities, white matter abnormalities, midline brain structure defects, cortical atrophy, and encephalomalacia. There was no uniformity for the clinical spectrum of CC anomalies. Microcephaly, developmental delay and seizures were the prominent findings in patients. The clinical features were more severe in cases with associated brain anomalies.

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.

Immobilization of 8-hydroxyquinoline onto silicone tubing for the determination of trace elements in seawater using flow injection ICP-MS.

A rapid and simple on-line method is described for the preconcentration of Mn, Co, Ni, Cu, Zn, Cd and Pb from sea water using 8-hydroxyquinoline immobilized onto silicone tubing (Sil-8-HQ) via the Mannich reaction. Recoveries between 35 and 95% and limits of detection in the ppt range were obtained using a 2 m long Sil-8-HQ tube with a sample flow rate of 1.0 ml min(-1). A tube could be subjected to sample loading and elution cycles over 200 times. The capacity was 1.5 and 1.3 mug cm(-2) for Cu and Mn, respectively. Cu, Cd, Co, Pb, Mn, Zn and Ni were determined in coastal and open ocean seawater using flow injection inductively coupled plasma mass spectrometry (FI-ICP-MS). Good agreement with certified values for the certified reference materials NASS-4 and CASS-3 was demonstrated when quantitation was undertaken by the method of additions.

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.

Acute alternating hemiplegia. A case report.

Acute alternating hemiplegia in childhood is a rare disorder characterized by onset before 18 months of age and frequent attacks of alternating paralysis. In this case report, a 20-month-old boy having the diagnosis of acute alternating hemiplegia is presented. The diagnosis was based on clinical features. The frequency and severity of the hemiplegic attacks decreased following flunarizine therapy. In this case, cerebral perfusion was investigated during ictal and interictal periods. Tc-99m HMPAO-Brain single photon emission computed tomography (SPECT) revealed normal cerebral perfusion in ictal periods and hypoperfusion in interictal periods.

Hypozincaemia in febrile convulsion.

UNLABELLED: To understand further the role role of trace elements in pathogenesis of febrile convulsions, serum zinc (Zn), copper (Cu), magnesium (Mg) and CSF An, Cu, Mg and protein levels were measured by spectrometry in patients with febrile convulsion (n = 19), bacterial meningitis (n = 9), viral CNS infection (n = 16) and in the control group (n = 10) which consisted of children with signs of meningeal irritation due to upper respiratory tract infection but normal CSF findings. Samples were obtained within 6 h after admission to hospital. Mean serum and CSF Zn levels in the febrile convulsion group were significantly lower than in the other groups (for serum Zn: 0.66 +/- 0.03 mg/1 vs 0.98 +/- 0.07 mg/1, 1.06 +/- 0.08 mg/1, 1.05 +/- 0.09 mg/1 P < 0.05; for CSF Zn: 22.96 +/- 1.62 micrograms/1 vs 75.47 +/- 6.9 micrograms/1, 50.32 +/- 5.235 micrograms/1, 39.85 +/- 2.81 micrograms/1 P < 0.05). A linear relationship was established between serum Zn and CSF Zn levels (P < 0.001). Mean CSF Zn, Cu and protein levels in the bacterial meningitis group were significantly higher than in the other groups (for CSF Cu 63.94 +/- 6.33 micrograms/1 vs 38.77 +/- 2.70 micrograms/1, 35.84 +/- 3.48 micrograms/1, 33.86 +/- 2.88 micrograms/1 P < 0.05; for CSF protein 0.80 +/- 0.12 g/1 vs 0.22 +/- 0.02 g/1, 0.53 +/- 0.08 g/1, 0.19 +/- 0.01 g/1 P < 0.05). In children with meningitis, the elevation of the mean CSF Zn and Cu levels may result from the breakdown of the blood-brain barrier and subsequent leakage of trace elements and protein from serum to CSF. There was no significant difference between the four groups in terms of mean serum Mg and mean CSF Mg levels. CONCLUSION: Serum and CSF Zn levels are decreased in children with febrile seizures. Zinc deprivation may play a role in the pathogenesis of febrile seizures.