Cutaneous application of menthol 10% solution as an abortive treatment of migraine without aura: a randomised, double-blind, placebo-controlled, crossed-over study.

OBJECTIVE: To investigate the efficacy and safety of the cutaneous application of menthol 10% solution for the abortive treatment of migraine. BACKGROUND: Peppermint and its active ingredient menthol have long been used for the treatment of various pain conditions including headache. METHODS: This is a randomised, triple-blind, placebo-controlled, crossed-over study conducted in the neurology Clinic of Nemazee Hospital, affiliated with Shiraz University of Medical Sciences, Shiraz, southern Iran, from March 2007 to March 2008. The patients were recruited via local newspaper advertisements. Eligible patients were categorised into two groups and a 10% ethanol solution of menthol (as drug) and 0.5% ethanol solution of menthol (as placebo) were applied to the forehead and temporal area in a crossover design. Pain free, pain relief, sustained pain free and sustained pain relief end-points were measured by questionnaires using a visual analogue scale. RESULTS: The intent-to-treat population consisted of 35 patients (80% women, 20% men, mean age: 29.6 +/- 6.2) with 118 migraine attacks. In the intent-to-treat population, the menthol solution was statistically superior to the placebo on 2-h pain free (p = 0.001), 2-h pain relief (p = 0.000), sustained pain free and sustained pain relief end-points (p = 0.008). The menthol solution was also more efficacious in the alleviation of nausea and/or vomiting and phonophobia and/or photophobia (p = 0.02). In the per-protocol population, there was significantly higher number of patients who experienced at least one pain free/pain relief after the application of menthol rather than the placebo (p = 0.002). No significant difference was seen between the adverse effects of the drug and the placebo groups (p = 0.13). CONCLUSION: Menthol solution can be an efficacious, safe and tolerable therapeutic option for the abortive treatment of migraine.

Proton pump inhibitors: predisposers to Alzheimer disease?

The abnormal processing of amyloid-beta peptide (A beta) and resultant formation of fibrillar A beta (fA beta) are major events in the pathogenesis of Alzheimer disease (AD). Microglia as the phagocytic cells of the brain can engulf and digest fA beta within their acidic lysosomes. The lysosomes of AD patients are less acidic and therefore less capable of clearance of fA beta. Vacuolar proton pumps (V-ATPases) which are found abundantly in microglia and macrophages, acidify lysosomes by pumping protons into these structures. Proton pump inhibitors (PPIs) can inhibit V-ATPases of the lysosomes. These drugs are shown to penetrate the blood-brain barrier in animals. PPIs are consumed for long periods in conditions such as gastroesophageal reflux disease, with the resultant exposure of the human brain to the substantial amounts of PPIs. We hypothesize that by blocking the V-ATPases on microglial lysosomes, PPIs may basify lysosomes and hamper degradation of fA beta. Chronic consumption of PPIs may thus be a risk factor for AD.

Cytotoxic T lymphocyte associated antigen-4 exon 1 A/G polymorphism in Iranian patients with multiple sclerosis.

BACKGROUND: Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a T-cell surface receptor of activated T cells. MATERIAL AND METHODS: We studied 100 Iranian patients with clinically definite multiple sclerosis (MS) and 100 ethnic, sex- and age-matched controls. CTLA-4 exon 1 A/G polymorphism was compared amongst patients and controls. RESULTS: There was no statistically significant difference in the allelic [odds ratio (OR): 1.19, confidence interval (CI) 95%: 0.76-1.85, P = 0.4] and genotypes (OR: 1.60, CI 95%: 0.911-2.824, P = 0.102) distribution amongst patients and controls. Also gender, course and progression index did not reveal any statistically significant differences in allele and genotype distribution of A/G polymorphism. CONCLUSION: As a non-European patient population, our results are consistent with the major previous studies showing no significant associations between CTLA4 exon 1 polymorphism and neither MS nor any of its subtypes.

Intercellular adhesion molecule-1 gene polymorphism in Iranian patients with multiple sclerosis.

Intercellular adhesion molecule-1 (ICAM-1), an important molecule in leucocyte activation and migration, is expressed on the CNS endothelial cells of patients with multiple sclerosis. This study was conducted to determine whether ICAM-1 gene polymorphism influences the risk of developing multiple sclerosis in an Iranian population. We studied 157 patients with definite multiple sclerosis and 156 ethnically matched controls. The patients and the controls were genotyped for ICAM-1 gene polymorphism at codons 241 (exon 4) and 469 (exon 6). G/R241 and K/E 469 allele and genotype distribution did not show any significant difference between patient and control groups. We concluded that role of the ICAM-1 gene polymorphisms in the pathogenesis of multiple sclerosis is still controversial and should be studied further.

Validity and reliability of the Persian version of the multiple sclerosis quality of life questionnaire.

BACKGROUND AND AIMS: To translate and test the reliability and validity of the Multiple Sclerosis Quality of Life Questionnaire (MSQoL-54) in Iranian MS patients. SETTING AND DESIGN: Using a standard "forward-backward" translation, cognitive debriefing and cultural adaptation procedure, the English version of the MSQoL-54 was translated to Persian which is the Iranian official language. MATERIALS AND METHODS: The subjects were multiple sclerosis (MS) patients referred to Motaharri clinic, Shiraz, South of Iran. Demographic data were recorded. Epidemiological data concerning MS type, duration of the disease, Functional System Score (FSS) and Expanded Disability Status Scale (EDSS) of patients were also provided by a qualified neurologist. STATISTICAL ANALYSIS: The reliability of the questionnaire was assessed by Cronbach's alpha coefficient. Construct validity was assessed through factor analysis. Factor analysis was performed to determine that the Persian version is a two-dimensional measure including physical and mental parameters. RESULTS: Multiple sclerosis patients (female:106 (75.2%), male:35 (24.8%)), with a mean+/-SD age of 32.2+/-9.8 years were enrolled in the study. Cronbach's alpha was 0.962. There were no significant differences between each item and the mean of physical and mental scores of MSQoL-54, regarding sex, marital status and education. There was a negative significant correlation between EDSS and physical health, role limitation due to physical problems, pain, energy, health perception, social function, cognitive function, health distress, overall Quality of Life. The scaling success rates were 100%, demonstrating convergent validity of each scale. Factor analysis confirmed the construct validity of the questionnaire. CONCLUSIONS: The Persian version of the MSQoL-54 questionnaire has a good structural characteristic, it is a reliable and valid instrument and can be used for measuring the effect of MS on the Quality of Life.

Neurological complications of first 100 orthotopic liver transplantation patients in southern Iran.

Neurological complications which are responsible for significant mortality and morbidity after orthotopic liver transplantation have been reported in 8.3% to 47% of cases in various series. This prospective study was performed to investigate the prevalence and characteristics of neurological complications in the first 100 patients who have undergone orthotopic liver transplantation from 1993 to 2004. Neurological symptoms and signs as well as routine laboratory tests, including complete blood cell counts, electrolyte levels, drug levels, microbiologic and serological studies, brain computed tomography scans, magnetic resonance imaging, and electrodiagnostic studies were reviewed in all patients. Follow-up periods were from 2 months to 10 years. Nineteen patients of mean age of 34.9 years developed neurological complications after orthotopic liver transplantation. The most common neurological symptoms and signs were confusion (42.1% of cases with neurological complications), convulsions (36.8%), and hallucinations (31.6%). Hepatic encephalopathy (31.6%) and drug toxicity (26.2%) were the most common neurological syndromes. The mortality rate was significantly higher among patients with neurological complications. Compared to other centers, neurological complications were less common in our center.

CSF levels of cytokines in neuro-Behçet's disease.

BACKGROUND: Neurological manifestations of Behçet's disease (neuro-Behçet's disease) present in 5-30% of patients. Although cytokines play a pivotal role in pathogenesis of Behçet's disease, published studies about the cerebrospinal fluid (CSF) levels of cytokines in neuro-Behçet's disease are scanty. METHODS: Nine patients with active parenchymal, one patient with non-parenchymal neuro-Behçet's disease, six patients with headache attributed to Behçet's disease, 13 patients with viral meningitis, and 19 healthy controls were recruited. Interleukin 6, 8, 10, tumor necrotic factor-alpha, and interferon-gamma were measured in the CSF using enzyme-linked immunosorbent assay method. RESULTS: Patients with viral meningitis had significantly higher levels of all investigated cytokines except for interferon-gamma in comparison with the patients with parenchymal neuro-Behçet's disease, headache attributed to Behçet's disease and controls (P values <0.05). CSF interleukin 6 was significantly higher in patients with parenchymal neuro-Behçet's disease in comparison with the controls (P=0.025). CSF levels of investigated cytokines had no significant difference between patients with headache attributed to Behçet's disease and controls (P values >0.05). Patients with headache attributed to BD and patients with parenchymal NBD had no significant difference in measured cytokines (P values >0.05). CONCLUSION: In contrast to some previous studies, our investigation showed loss of analogy between CSF cytokine profiles of patients with parenchymal neuro-Behçet's disease and viral meningitis. Also we postulated a crucial role for interleukin 6 in immunopathogenesis of neuro-Behçet's disease.

Methanol poisoning: acute MR and CT findings in nine patients.

INTRODUCTION: Methanol poisoning is an uncommon but potent central nervous system toxin. We describe here the CT and MR findings in nine patients following an outbreak of methanol poisoning. METHODS: Five patients with a typical clinical presentation and elevated anion and osmolar gaps underwent conventional brain MRI with a 1.5-T Gyroscan Interna scanner. In addition nonenhanced CT was performed in another three patients with more severe toxicity. RESULTS: Bilateral hemorrhagic or nonhemorrhagic necrosis of the putamina, diffuse white matter necrosis, and subarachnoid hemorrhage were among the radiological findings. Various patterns of enhancement of basal ganglial lesions were found including no enhancement, strong enhancement and rim enhancement. CONCLUSION: A good knowledge of the radiological findings in methanol poisoning seems to be necessary for radiologists. The present study is unique in that it enables us to include in a single report most of the radiological findings that have been reported previously.

Neuro-Behcet's disease: a masquerader of multiple sclerosis. A prospective study of neurologic manifestations of Behcet's disease in 96 Iranian patients.

Behcet's disease is a multisystem vasculitis. Its neurologic complications include different syndromes. The purpose of this investigation was to study the prevalence of neurologic manifestations among patients with Behcet's disease and to determine the frequency of different symptoms, signs, and syndromes in neuro-Behcet's disease. Ninety-six consecutive patients who were referred to the Behcet's Disease Clinic in Shiraz (southern Iran) were interviewed and thoroughly examined. Psychiatric evaluation, CSF analysis, electroencephalography, electrodiagnostic studies, and neuroradiologic imaging (preferably MRI) were performed in appropriate cases. Six patients (6.3%) had definite neuro-Behcet's disease. They were 4 males and 2 females (mean age 37.5 years). In 2 patients Behcet's disease had not been diagnosed before. The most frequent symptoms of neuro-Behcet's disease were headache (83.3%), paresthesia (83.3%), unsteadiness (66.7%), diplopia (66.7%), and weakness (50%). The most frequent signs were gait abnormalities (66.7%), sensory abnormalities (66.7%), ophthalmoplegia (50%), cerebellar ataxia (50%), and hemiplegia (50%). The most common syndrome was brain-stem+ type (50%). Subacute onset and relapsing-remitting course were the most common temporal patterns. Neurological manifestation is a relatively less frequent complication of Behcet's disease but it produces severe disabilities. It must be considered in differential diagnosis of multiple sclerosis.