Celiac disease in patients with neuropathy

Background: Neuropathy means nerve damage, which interferes with the functioning of the peripheral nervous system. It has been mentioned as one of the extra-intestinal manifestations of celiac disease. This study aimed to investigate the prevalence of celiac disease in patients presented with idiopathic neuropathy

Materials and Methods: A cross-sectional study was done in patients with idiopathic neuropathy at Shariati Hospital, Tehran. Serological tests including endomysial IgA, tissue transglutaminase [TTG] IgA and IgG, and DGP[deamidated gliadin peptide] IgA, and genetic assessment for HLA DQ2 and DQ8[human leukocyte antigen] were done for all patients and those who had positive celiac serology and HLA DQ2/DQ8 underwent endoscopy and adequate biopsy samples were taken. Diagnosis was made based on histopathological report of celiac disease

Results: 101 patients with idiopathic neuropathy were enrolled. The mean age was 43.56+/-10.66 years [range 70-18 years]. The prevalence of HLA-DQ2 and HLA-DQ8 positivity in patients with idiopathic neuropathy was 36.6% and 9.9%, respectively. The most common neuropathy subtype in patients with positive HLA-DQ2 and DQ8 was demyelinating PN[peripheral neuritis]. One patient [1%] was diagnosed as havine celiac disease

Conclusion: Although the prevalence of celiac disease in patients with idiopathic neuropathy was similar to the general population, having considered the pravalence of celiac disease, treating this condition with gluten-free diet is of importance

Mitochondrial copy number and d-loop variants in Pompe patients

Objective: Pompe disease is a rare neuromuscular genetic disorder and is classified into two forms of early and late-onset. Over the past two decades, mitochondrial abnormalities have been recognized as an important contributor to an array of neuromuscular diseases. We therefore aimed to compare mitochondrial copy number and mitochondrial displacement-loop sequence variation in infantile and adult Pompe patients

Materials and Methods: in this retrospective study, the mitochondrial D-loop sequence was analyzed by polymerase chain reaction [PCR] and direct sequencing to detect possible variation in 28 Pompe patients [17 infants and 11 adults]. Results were compared with 100 healthy controls and sequences of all individuals were compared with the Cambridge reference sequence. Real-time PCR was used to quantify mitochondrial DNA copy number

Results: among 59 variants identified, 37[62.71%] were present in the infant group, 14[23.333%] in the adult group and 8[13.333%] in both groups. Mitochondrial copy number in infant patients was lower than adults [P<0.05]. A significant frequency difference was seen between the two groups for 12 single nucleotide polymorphism [SNP]. A novel insertion [317-318 ins CCC] was observed in patients and six SNPs were identified as neutral variants in controls. There was an inverse association between mitochondrial copy number and D-loop variant number [r=0.54]

Conclusion: the 317-318 ins CCC was detected as a new mitochondrial variant in Pompe patients

Granulocyte Colony-Stimulating Factor for Amyotrophic Lateral Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study of Iranian Patients

BACKGROUND AND PURPOSE: The aim of this study was to determine the efficacy and tolerability of granulocyte colony-stimulating factor (G-CSF) in subjects with amyotrophic lateral sclerosis (ALS). METHODS: Forty subjects with ALS were randomly assigned to two groups, which received either subcutaneous G-CSF (5 microg/kg/q12h) or placebo for 5 days. The subjects were then followed up for 3 months using the ALS Functional Rating Scale-Revised (ALSFRS-R), manual muscle testing, ALS Assessment Questionnaire-40, and nerve conduction studies. CD34+/CD133+ cell count and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated at baseline. RESULTS: The rate of disease progression did not differ significantly between the two groups. The reduction in ALSFRS-R scores was greater in female subjects in the G-CSF group than in their counterparts in the placebo group. There was a trend toward a positive correlation between baseline CSF MCP-1 levels and the change in ALSFRS-R scores in both groups (Spearman's rho=0.370, p=0.070). CONCLUSIONS: With the protocol implemented in this study, G-CSF is not a promising option for the treatment of ALS. Furthermore, it may accelerate disease progression in females.

Stress differentially predicts multiple sclerosis relapses

Background and Objective: For decades, stress has been postulated as a risk factor for multiple sclerosis (MS) relapses. Because of conflicting results in previous studies we conducted a prospective study to investigate this relationship in a less studied, Middle Eastern population. Methods: In this prospective study, 57 Iranian MS patients were followed trimonthly for 12 months. Possible stressful events (measured with validated Persian version of Paykel’s questionnaire) and quality of life (measured with validated Persian version of the Multiple Sclerosis Impact Scale questionnaire) were assessed in successive visits in addition to other variables. Relapses were enquired and confirmed clinically by a Neurologist. Main analysis was done by use of Mixed Generalized Linear Model. Results: Mean age of the participants was 33.5±7.4 years, 81% were females, and all were receiving interferons. Number of stressors, not the stress severity measures, reached near significance in predicting relapses (p=0.054), and showed a trend towards significance in predicting severe relapses (p=0.082). Education and number of previous relapses were the only variables that had a near significance interaction with number of stressors in its association with MS relapse. This association was only significant among subjects with less than college education (P=0.008) and subjects with more than 2 relapses (p=0.038). Conclusion: Number of stressors, not their severity, was associated with MS relapses among Iranian patients. This association had interaction with education and history of previous relapses; it was significant only among lower educated patients or patients with more prior relapses.

role of cytomegalovirus haemophilus influenzae and epstein barr virus in guillain barre syndrome

Guillain Barre Syndrome [GBS] is an inflammatory, usually demyelinating, polyneuropathy; clinically characterized by acute onset of symmetric progressive muscle weakness with loss of myotatic reflexes. Thirty five patients with GBS, defined clinically according to the criteria of Asbury and Cornblath, were recruited from three hospital affiliated to Tehran University of Medical Sciences. Controls: As a control group 35 age and sex matched patients with other neurological diseases admitted to the same hospital at the same time, were included in our study. Serum samples were collected before treatment from each patient [within 4 weeks after the disease onset] and controls, and stored frozen at -80°C until serologic assays were done. Serologic testing of pretreatment serum was performed in all patients. Positive titer of virus specific IgM antibody against cytomegalovirus [CMV] was found in 6 cases and 2 controls. 34 patients and 31 controls had high titer of anti Haemophilus influenzae IgG and one patient had serologic evidence of a recent Epstein Barr virus [EBV] infection. The mean titer of IgG antibody against Haemophilus influenzae in cases and controls was 5.21 and 2.97 respectively. Although serologic evidence of all these infections were more frequent in cases than in controls, only Haemophilus influenzae infection appeared to be significantly related to GBS [P=0.002]. Eleven cases and 3 controls had high titers of IgG antibody against Haemophilus influenzae type B [titer >8]. There is significant association between high titer of IgG antibody against Haemophilus influenzae and GBS [MX017]. Our results provide further evidence that Haemophilus influenzae and probably CMV, can be associated with GBS

Increased Prevalence 12308 A > G mutation in Mitochondrial tRNA[Leu [CUN]] Gene Associated with earlier Age of Onset in Friedreich Ataxia

Friedreich ataxia [FRDA] is an inherited recessive disorder. Mitochondrial DNA is a candidate modifying factor for FRDA.The purpose of this study was to investigate the relationship between the tRNA[Leu [CUN]] 12308 A> G mutation and age of onset in Friedreich ataxia. The 12308 A> G substitution in mitochondrial tRNA[Leu [CUN]] was examined in DNA samples from 30 Friedreich ataxia patients and 48 control subjects by temporal temperature gradient gel electrophoresis [TTGE] and sequencing. Logistic regression was used to determine of cutoff age of onset. Twenty-two patients had the 12308 A> G mutation, and we found that its overall prevalence was significantly higher in 20 patients aged 17 years or younger than in 2 patients aged over 17 years [90% versus 10%]. The 12308 A> G mutation lies in a region that has been highly conserved between species. Our results show that the 12308 A > G mutation is associated with earlier age of onset in Friedreich ataxia. Thus, this mutation might cause the younger age of onset in FRDA

[Genotype-phenotype correlations in an iraninan myotonic dystrophy cohort]

Myotonic Dystrophy type I [DM1] the most common form of muscular dystrophy in adults affecting 1/800 individuals is a dominantly inherited disorder with a multi-systemic pattern affecting skeletal muscle, heart, eye, endocrine and central nervous system. DM1 is associated with the expansion and instability of a trinucleotide [CTG] repeat in the 3 untranslated region of the myotonic dystrophy protein kinase [DMPK] gene located on choromosome 19q13.3. The normal copy number is 5-37 CTG repeat whereas it is expanded in DM1 patients and the expansion size broadly correlates with the severity of the symptoms. The aim of this study was to determine the clinical and genetic characteristic of DM1 in Iranian patients for genotype-phenotype correlation methods. Clinical assessment was based on the muscular disability rating scale [MDRS] and a sum of symptoms score [SSS]. Molecular analysis [PCR and Southern blot] was used to clarify uncertain clinical diagnoses and confirm the clinical findings. Forty six patients from twenty five DM1 families were reviewed. In all the DM1 patients, the wide clinical symptoms confirmed the reported phenotypic vaiability of disorder. The range of CTG expansion of the mutated allele was 97-833 CTG repeats and an inverse correlation between age of onest and repeat length was observed. A clear relation between the size of the CTG repeat and the clinical disease score [MDRS] was found but not with SSS. No correlation was seen between the endocrine dysfunction and the expansion size in DM1 patients