Genetic variations in tumor necrosis factor alpha, interleukin-10 genes, and migraine susceptibility.

OBJECTIVES: Migraine is a very common headache disorder and pathogenesis of the disease is still largely unknown. Cytokine genes have been implicated in migraine susceptibility. The present study was designed to explore the associations of polymorphisms in the tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10) gene, and IL-10 haplotypes in Turkish migraine patients. METHODS: TNF-α-308G/A, IL-10 -1082G/A, -819C/T, and -592C/A polymorphisms in 203 migraine patients and 202 healthy subjects were analyzed by using amplification refractory mutation system-polymerase chain reaction. RESULTS: The -308G/A genotypic and -308A allelic frequency of TNF-α polymorphism was higher in migraine patients than healthy controls, and significant association was found between migraine and TNF-α-308G/A polymorphism (Bonferroni correction [Pc]: <0.0001, odds ratio: 2.16, 95% confidence interval: 1.44-3.28). No statistically significant association was found between IL-10 -1082G/A, -819C/T, and -592C/A polymorphisms and haplotypes containing these alleles and migraine. CONCLUSIONS: This study reflect that TNF-α-308G/A polymorphism may be one of the many genetic factors for migraine susceptibility in the Turkish population.

Retrospective approach to methylenetetrahydrofolate reductase mutations in children.

Methylenetetrahydrofolate reductase reduces methyltetrahydrofolate, a cosubstrate in the remethylation of homocysteine, from methylenetetrahydrofolate. Congenital defects, hematologic tumors, and intrauterine growth retardation can occur during childhood. This study evaluated clinical and laboratory treatment approaches in children diagnosed with methylenetetrahydrofolate reductase mutations. Our group included 23 boys and 14 girls, aged 103.4 ± 70.8 months S.D. Clinical findings of patients and homocysteine, vitamin B12, folate, hemogram, electroencephalography, cranial magnetic resonance imaging, and echocardiography data were evaluated in terms of treatment approach. Our patients' findings included vitamin B12 at 400.4 ± 224.6 pg/mL S.D. (normal range, 300-700 pg/mL), folate at 10.1 ± 4.5 ng/mL S.D. (normal range, 1.8-9 ng/mL), and homocysteine at 8.4 ± 4.7 µmol/L S.D. (normal range, 5.5-17 µmol/L). Eighty-eight percent of patients demonstrated clinical findings. In comparisons involving categorical variables between groups, χ(2) tests were used. No relationship was evident between mutation type, laboratory data, and clinical severity. All mothers who had MTHFR mutations and had babies with sacral dimples had taken folate supplements during pregnancy. To avoid the risk of neural tube defects, pregnant women with a MTHFR mutation may require higher than normally recommended doses of folic acid supplementation for optimum health.

NRAMP1 (SLC11A1) variants: genetic susceptibility to multiple Sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is an inflammatory, autoimmune demyelinating disease of the central nervous system. Human Natural Resistance Associated Macrophage Protein 1 (NRAMP1) gene polymorphisms have been implicated in the immune mediated diseases susceptibility. This study aimed to investigate the plausible association between NRAMP1 gene and MS susceptibility. METHODS: We analyzed (GT)(n,) INT4, 3'UTR and D543N polymorphisms of NRAMP1 gene in 100 MS patients and 104 healthy subjects by using amplification refractory mutation system-polymerase chain reaction and sequence analysis. RESULTS: No significant association was found between (GT)(n,) INT4, 3'UTR and D543N polymorphisms and MS. There was also no correlation between NRAMP1 polymorphisms and MS clinical forms. CONCLUSIONS: Our findings suggest that NRAMP1 polymorphisms do not play a role in MS susceptibility and clinical finding of MS in Turkish patients.

Phenotypic differences in a large family with Kennedy's disease from the Middle Black Sea region of Turkey.

We report the clinical and electrophysiological features of a large Turkish family with genetically confirmed X-linked spinal and bulbar muscular atrophy (SBMA). Family members were identified by field work. A detailed history was obtained from each subject, and each subject received a detailed neurological examination. To confirm the CAG repeat expansion in the AR gene, genomic DNA was extracted from the peripheral blood of patients. The family consisted of 128 individuals over five generations, with two consanguineous parents, one slightly affected female, and 12 affected males with SBMA. We studied the five surviving male patients and one surviving female carrier. The age at disease onset, phenotypic features, and disease severity varied among the family members. DNA analysis was performed on five individuals, belonging to five generations of the family. Four affected males and a slightly affected female carrier were shown to carry an expanded CAG repeat in the androgen receptor gene. This family report is consistent with previous studies suggesting that SBMA may be present with a wide clinical spectrum in affected family members. Further descriptions of SBMA affected families with different ethnic backgrounds may assist in identifying possible phenotypic and genetic features of the disease.

Combination of myotonic dystrophy and hereditary motor and sensory neuropathy.

Myotonic Dystrophy Type 1 (DM1) in combination with demyelinating neuropathy is very rare in literature. In this study, DM1 and demyelinating neuropathy were demonstrated clinically and electromyographically in a 43-year-old female patient from Turkey. In the patient an expanded CTG repeat in the Myotonic Dystrophy Protein Kinase (DMPK) gene was confirmed in combination with a duplication in the Charcot-Marie-Tooth Disease (CMT1A) gene. DM1 was also determined in her 25-year-old son.

Intra-familial incidence and characteristics of hot water epilepsy.

OBJECTIVE: To assess the clinical features of several members of the same family diagnosed with both hot water epilepsy (HWE) and cerebral lesions. METHODS: Age at onset and types of seizure, precipitating factors, EEG findings, and neuroimages were evaluated. RESULTS: The family consisted of six generations, including one consanguineous parent. Of eight family members diagnosed with epilepsy, seven suffered from HWE. Age at onset of seizures ranged within childhood. Seven patients with HWE experienced complex partial seizures, with or without secondary generalization; one experienced simple partial seizures as well as complex partial seizures. Three patients experienced spontaneous seizures as well as HWE. Interictal EEG revealed abnormalities in two patients. Magnetic resonance imaging revealed cerebral lesions in one patient, probably attributable to ischemic changes. Magnetic resonance images were consistent with findings of ischemic gliosis in two patients, and either demyelinating or ischemic gliosis in one patient. CONCLUSIONS: Descriptions of HWE families with different ethnic backgrounds may permit more definite conclusions regarding the mechanisms epileptogenesis, and the genetic defects that underlie this disease.

Bell's palsy and choreiform movements during peginterferon alpha and ribavirin therapy.

Neuropsychiatric side effects of long-term recombinant interferon-alpha therapy consist of a large spectrum of symptoms. In the literature, cranial neuropathy, especially Bell's palsy, and movement disorders, have been reported much less often than other neurotoxic effects. We report a case of Bell's palsy in a patient with chronic hepatitis C during peginterferon-alpha and ribavirin therapy. The patient subsequently developed clinically inapparent facial nerve involvement on the contralateral side and showed an increase in choreic movements related to Huntington's disease during treatment.

Carpal tunnel syndrome in postmenopausal women.

OBJECTIVE: Hormonal changes that accompany menopause have a significant impact on the nervous and other physiological systems. Our objective was to evaluate the relationship between carpal tunnel syndrome (CTS) and the clinical features of menopause in postmenopausal women, in comparison to age-matched healthy controls. METHODS: Overall, 6230 women were seen during the study period. Of these, 5587 were not eligible because they were premenopausal or perimenopausal. 537 women did not meet the criteria used in the study for a diagnosis of idiopathic CTS and were excluded. Finally, one hundred and six patients with CTS and 115 controls were examined. The presence of CTS was confirmed both clinically and electrophysiologically. Socio-demographic variables and reproductive histories were evaluated via a structured interview. RESULTS: In comparison to healthy controls, patients with CTS showed a significantly greater number of pregnancies and an earlier age at menopause. Regarding the type of menopause, patients and controls showed similar frequencies for natural versus surgical menopause. The frequency of natural menopause was significantly higher than that of surgical menopause in both groups. CONCLUSION: Our results suggest that age at menopause may be a significant factor in the development of CTS. Pregnancy-related hormonal changes may have long-term effects that increase the incidence of CTS in postmenopausal women.

Obesity and carpal tunnel syndrome: is there a causal relationship?

OBJECTIVES: Obesity is defined as a risk factor for carpal tunnel syndrome (CTS). In this study, the presence or absence of recovery in median nerve conduction velocities after weight loss in obese patients was assessed in order to determine whether excess weight or other factors influence the higher prevalence of CTS in obese patients. METHODS: Patients with body mass indexes (BMIs) >or=30 were included in the study. CTS symptoms, age, gender, height, body weight, and concomitant diseases were evaluated. Nerve conduction studies (NCS) were obtained on one upper extremity. All patients were included in dietetic programs. Three months later, NCS were repeated and compared with the first NCS. RESULTS: BMIs were statistically significantly lower on the second visits 3 months later (p = 0.0001). No statistically significant difference was observed in the second NCS of electromyographically diagnosed cases with CTS (p > 0.05). CONCLUSION: We expected a recovery in median nerve conduction velocities in patients with CTS after weight loss. In the literature, even in untreated cases with CTS, spontaneous improvements in second NCS have been reported. This finding suggests that factors other than excess body weight may be influential in the higher prevalence of CTS in obese patients. A more detailed, genetic-factor-targeted investigation may prove more beneficial to clarify this issue.