Severe Relapses of Neuromyelitis Optica Spectrum Disorder During Treatment With Dimethyl Fumarate.

ABSTRACT: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system, characterized by a specific antibody that selectively binds aquaporin-4 channel.This is a report of an NMOSD case, with severe attacks of optic neuritis and myelitis after initiate of dimethyl fumarate (DMF).We suggested that DMF could deteriorate the neuromyelitis optica (NMO) disease course, which results in serious morbidity and mortality in patients. Thus, initiation of DMF should be avoided before ruling out NMOSD in patients experiencing demyelinating attacks, especially in the case of recurrent optic neuritis or myelopathy and concurrency of other rheumatologic diseases.

Clinicogenetical Variants of Progressive External Ophthalmoplegia - An Especial Review of Non-ophthalmic Manifestations.

Progressive external ophthalmoplegia (PEO) is a slowly progressive myopathy characterized by extraocular muscles involvement, leading to frozen eyes without diplopia. The pattern of inheritance may be mitochondrial, autosomal dominant or, rarely, autosomal recessive. Sporadic forms were also reported. Muscular involvement other than extraocular muscles may occur with varying degrees of weakness, but this mostly happens many years after the disease begins. There are also scattered data about systemic signs besides ophthalmoplegia. This article aims to review non-ophthalmic findings of PEO from a clinicogenetical point of view.

Safety and efficacy of memantine for multiple sclerosis-related fatigue: A pilot randomized, double-blind placebo-controlled trial.

BACKGROUND: Fatigue is one of the most common symptoms in patients with multiple sclerosis (MS). Currently, there is no approved medication for MS-related fatigue. OBJECTIVE: In this study, we aim to evaluate the safety and efficacy of memantine for improving fatigue in patients with MS. METHODS: This was a pilot randomized, double-blind, placebo-controlled clinical trial. Eligible patients with relapsing-remitting MS (RRMS) according to the McDonald criteria were randomized to receive either memantine (20 mg/day) or placebo and were assessed at baseline and three months after treatment. The change in the severity of fatigue was determined by the Modified Fatigue Impact Scale (MFIS). RESULTS: Sixty-four patients were randomly allocated to the memantine (n = 32) and placebo (n = 32) groups. Sixteen patients in the memantine group and 24 patients in the placebo group completed the study. The mean [95% CI] absolute change in MFIS scores from baseline did not differ significantly between the memantine (-5.8 [-12.7 to 1.0]) and placebo (-4.0 [-10.6 to 2.7]) groups (between-group difference: -1.9 [-11.7 to 7.8], P = .702). No serious adverse events were reported, except for dizziness and sedation in four patients in the experimental arm, which resulted in discontinuation. CONCLUSION: This trial failed to prove any clinical efficacy of memantine for the management of MS-related fatigue. Although memantine was generally well-tolerated, adverse events were among the major causes of dropout in this study.

Descriptive epidemiology: prevalence, incidence, sociodemographic factors, socioeconomic domains, and quality of life of epilepsy: an update and systematic review.

INTRODUCTION: The purpose of this study was to investigate the contributions of quality of life (QOL), sociodemographic factors (age, sex, etc.), residential areas, general attitudes toward epilepsy, socioeconomic domains, prevalence and incidence in epileptic patients from Iran. MATERIAL AND METHODS: A systematic literature search was conducted, including database searches in PubMed, Medline, Embase, ScienceDirect, Scopus, ISC, Health, Web of Science, and the Cochrane Library Database of relevant articles, personal files and systematic reviews to identify studies examining risk factors in epilepsy. RESULTS: This review article shows that certain socio-demographic and socio-economic factors, geographic variation in epidemiologic patterns of epilepsy as well as clinical factors may be crucial in determining QOL in epilepsy patients and provides further evidence supporting the validity of the scale in QOL based on consideration of different target groups in different areas. CONCLUSIONS: Prevalence of epilepsy appears to be correlated with socioeconomic status in the lower socioeconomic groups. Also demographic characteristics, socio-economic factors and clinical presentation are linked to different QOL of these patients among nations. The educational program has a beneficial effect on self-management behaviors in patients with epilepsy. More work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of people with epilepsy.

Cerebral Hyperperfusion Syndrome, an Unusual but Disastrous Complication of Carotid Recanalization: A Case Report.

Cerebral hyperperfusion syndrome (CHS), known as the dark side of carotid recanalization, happens in about 0%-3% of patients. Unfortunately, physicians involving in carotid recanalization generally are not aware of diagnostic and therapeutic aspects of this unusual but potentially life-threatening disorder. Severe bilateral carotid stenosis is suggested to predispose patients to CHS by decrement of cerebrovascular reactivity in a setting of chronic hypoperfusion state. We here introduced such a case; a 69-year-old man, a known case of hypertension and ischemic heart disease, who developed progressive intracranial hypertension underlying CHS after carotid stenting because of symptomatic severe bilateral carotid stenosis.

Differential serostatus of Epstein-Barr virus in Iranian MS patients with various clinical patterns.

Background: Epidemiological evidence suggests a role of Epstein-Barr virus (EBV) in triggering the pathogenesis of Multiple Sclerosis (MS). The aim of this study was to assess the EBV-specific antibodies in MS patients with various clinical patterns and their association with the production of IFN-γ, IL-12, and IL-4 cytokines compared with healthy individuals. Methods: We measured EBNA-1 IgG, VCA IgG, and production of IFN-γ, IL-12 and IL-4 cytokines in patients with different clinical patterns and healthy controls using ELISA method. Results: There was a higher titer of anti-EBV antibodies in MS patients compared to healthy controls. SPMS patients generated higher EBNA-1 levels than those with RRMS and PPMS patients whereas; the level of VCA IgG was higher in the RRMS patients than PPMS. In PPMS patients, a significant increase was found in IFN-γ and IL-12 cytokines compared to other subtypes, whereas IL-4 cytokine had a decreased level compared to RRMS patients. Higher anti-EBV antibodies are associated with increased IL-12 cytokine in RRMS patients. However, no significant correlation was found between these antibodies and other secreted cytokines. Conclusion: EBV infection is one of the strong risk factors for MS. Acting on these factors could be useful to decrease the incidence and disease exacerbation of MS. Study of the antibody levels to EBV virus could be useful for evaluating MS risk score in each clinical subtypes.

The comparison of anti-seizure and tocolytic effects of phenytoin and magnesium sulphate in the treatment of eclampsia and preeclampsia: A randomised clinical trial.

Background: To date, magnesium sulphate (MgSO4) is the treatment of choice for prevention of seizure in eclampsia and preeclampsia. However, there are some limitations in the administration of MgSO4 due to its tocolytic effects. The aim of this study was to compare the anticonvulsant and tocolytic effects of MgSO4 and another drug, phenytoin, in patients with eclampsia and preeclampsia. Methods: This clinical trial was conducted on pregnant women hospitalised with eclampsia or preeclampsia, during 2014-2016. The subjects were randomly assigned to two treatment groups using blocking method based on disease (eclampsia or mild and severe preeclampsia). One group received MgSO4 (group M) and another group received phenytoin (group P) as treatment. Each group consisted of 110 and 65 women with mild and severe preeclampsia, respectively (subgroup A), and 25 women with eclampsia (subgroup B). Duration of labor, the number of cesarean sections, convulsions and Apgar scores of infants were compared between the two groups and were considered as treatment outcomes. Results: Convulsion rate was significantly lower with MgSO4 than phenytoin (P = 0.001). No seizure occurred in patients with mild preeclampsia in group P. Duration of stage one of labor (P < 0.001) and the number of cesarean sections (P = 0.040) were significantly higher in group M. However, one-minute Apgar scores for newborns were higher in women treated with MgSO4 compared to that of phenytoin (P = 0.001). Five-minute Apgar was not significantly different. Conclusion: Although MgSO4 is more effective than phenytoin for prevention of convulsion in eclampsia and severe preeclampsia, phenytoin may be considered for treatment of special conditions such as mild preeclampsia. Due to the tocolytic effects of MgSO4 on increasing the duration of labor, the increased risk of cesarean section and the potential for toxicity, physicians should critically consider the best drug according to the condition of the patient.

MLC601 in vascular dementia: an efficacy and safety pilot study.

BACKGROUND AND AIM: Vascular dementia (VaD) is the second most common cause of dementia and currently there is scarcity of therapies for VaD. We aimed to investigate the efficacy and safety of MLC601 in the treatment of VaD. METHODS: In this multicenter, pilot, randomized, double-blind trial, 82 patients with VaD according to DSM-5 criteria received MLC601 or placebo capsules three times a day for 2 years. The primary efficacy end-point was evaluated by comparing Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) score between the two groups over 2 years of study. Safety was also assessed by recording adverse events and abnormal laboratory results. RESULTS: Eighty-one patients completed the study and were included in the analysis. One patient was lost to follow-up in the placebo group. After 2 years, mean (±SD) changes in the MMSE score were -3.71 (±4.50) for MLC601 group and -9.33 (±4.80) for placebo group. ADAS-cog score showed (±SD) changes of 7.34 (±9.55) and 19.00 (±11.28) for MLC601 and placebo group, respectively. Repeated measures analyses showed that both MMSE and ADAS-cog scores were significantly better in the treatment group at 24 months (p<0.001). Ten (24.39%) patients reported predominantly transient gastrointestinal adverse events in MLC601 group. No patient left the study due to adverse events. There were no clinically significant abnormalities on laboratory tests. CONCLUSION: Patients treated with MLC601 over the 2 years showed dramatically better cognitive outcome compared with those treated with placebo. MLC601 was devoid of any serious adverse events and was well-tolerated.

Memantine for Prophylactic Treatment of Migraine Without Aura: A Randomized Double-Blind Placebo-Controlled Study.

BACKGROUND: Uncontrolled studies in human have suggested that memantine might be a suitable option for migraine prophylaxis. OBJECTIVE: To assess the efficacy and tolerability of memantine for migraine prophylaxis. METHODS: This was a 12-week randomized double-blind placebo-controlled parallel-group study. Sixty patients with migraine without aura were randomized using a computer-generated list to receive memantine (10 mg/day) or placebo for 12 weeks. The primary outcome was the difference in change from baseline in the monthly attack frequency at week 12 between the two groups (using migraine diary). Secondary efficacy measures were assessed using several clinical, functional, and psychological instruments. We performed both complete case (CC) and intention-to-treat analyses (ITT). RESULTS: Twenty-five patients in the memantine group and 27 patients in the placebo group completed the study. Patients in the memantine group showed significantly greater reduction (mean change; 3.4; 95%CI, 2.3-4.4) in the monthly attack frequency than the placebo group (mean change, 1.0; 95%CI, 0.3-1.7) (mean difference [MD], 2.3; 95%CI, 1.1-3.5, P < .001). Both CC (MD, 4.9; 95%CI, 2.6-7.2 days), and ITT analyses (MD, 5.2; 95%CI, 2.0-8.5) showed significantly higher reduction in the mean number of migraine days in the memantine group than the placebo group (P < .01). Patients in the memantine group experienced greater reduction in the number of work absence days, severity, and disability score than the patients in the placebo group in both ITT and CC analyses. Changes in quality of life, sleep, depression, and anxiety did not differ between the two groups. Three patients in the memantine group complained of sedation, mild vertigo and nausea, and drowsiness. In the placebo group, one patient complained of nausea and another patient discontinued treatment after 2 weeks due to vertigo. CONCLUSION: Memantine might be a tolerable and efficacious option for prophylaxis in patients with migraine without aura. Tolerability, short duration required for titration, and safety profile in pregnancy might give memantine an advantage over other antimigraine medications. The study was registered in the Iranian Registry of Clinical Trials (Registration number: IRCT2013120115616N1).

Immunosuppressive Drugs, an Emerging Cause of Posterior Reversible Encephalopathy Syndrome: Case Series.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a well-recognized complication of hypertensive encephalopathy. Recently, pre-eclampsia, connective tissue disorders, and immunosuppressive drugs have been reported to be the etiologies of this rare syndrome. METHODS: We evaluated 9 cases of PRES whose diagnosis were confirmed based on clinical and radiologic evidence between July 2011 and December 2013 in a tertiary center, Imam Khomeini Hospital, Tehran, Iran. RESULTS: Immunosuppressive drugs, especially cyclosporine, and hypertension were the main precipitating factors. In this study, seizure was the most common clinical presentation (100%), whereas other common clinical presentations were confusion (78%), visual loss (67%), and headaches (67%). With conservative management and elimination of predisposing factor, the patients improved gradually except for 2 cases who experienced prolonged recovery period because of delayed diagnosis. CONCLUSIONS: With timely diagnosis, PRES generally has a good prognosis with complete recovery. However, in missed conditions, it could be associated with catastrophic burden especially in organ transplantation after a prolonged time spending to find matched donors or in chronic immunosuppressive conditions. Thereupon, physicians should be aware of clinical and radiologic manifestations of this preventable but potentially disabling syndrome.

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 µg/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 ρ=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.

Association of CD58 Polymorphism with Multiple Sclerosis and Response to Interferon ß Therapy in A Subset of Iranian Population.

OBJECTIVE: Multiple sclerosis (MS) is one of the leading neurodegenerative causes of physical disability world-wide. Genetic aberrations of autoimmunity pathway components have been demonstrated to significantly influence MS development. Cluster of Differentiation 58 (CD58) is pertained to a group of genes which had been assayed in several recent association studies. Given the significance of CD58 in modulation of T regulatory cells that control autoimmune responses, the present study was conducted to investigate the frequency of rs12044852 polymorphism and its effect on the outcome of interferon beta (IFN-ß) therapy in a subset of Iranian MS patients. MATERIALS AND METHODS: Two hundred MS patients and equal number of healthy controls were recruited to be genotyped in an experimental case-control based study through polymerase chain reaction using specific sequence primers (PCR-SSP). Relapsing remitting multiple sclerosis (RRMS) patients administered IFN-ß therapy were followed up with clinical visits every three months up to two years. The mean of multiple sclerosis severity score (MSSS) and expanded disability status scale (EDSS) were measured to monitor the change in severity of MS in response to IFN-ß therapy. Pearson's Chi-square and analysis of variance (ANOVA) tests were the main statistical methods used in this study. RESULTS: Strong association was found between the CC genotype and onset of MS (p=0.001, OR=2.22). However, there was no association between rs12044852 and various classifications and severity of MS. Pharmacogenetics-based analysis indicated that carriers of CC genotype had the highest MSSS score compared to others, implying a negative impact of rs12044852 on response to IFN-ß therapy. CONCLUSION: Taken together, our findings revealed the critical effect of rs12044852 polymorphism of CD58 on the progression of MS disease. This indicates that genotyping of MS patients may expedite achieving personalized medical management of MS patients.

Rare Association of Severe Cryptococcal and Tuberculosis in Central Nervous System in a case of Sarcoidosis.

Sarcoidosis is a multisystem noncaseating granulomatous disease with a propensity for lung, eye, and skin which recently have been proposed that mycobacterium tuberculosis may contribute in its pathogenesis, and rarely involves central nervous system (CNS). Despite CD4+ lymphocytopenia, sarcoidosis by itself does not increase risk of opportunistic infections other than cryptococcosis. Nonetheless, simultaneous association of CNS cryptococcosis and tuberculosis infection remains extremely rare event in immunocompetent states, and has not been reported in sarcoidosis yet. We here presented such a case in a 42 years old man, a known case of sarcoidosis with diagnostic and therapeutic difficulties were encountered in a fourteen-month-long hospitalization period.

Islamic fasting and multiple sclerosis.

BACKGROUND: Month-long daytime Ramadan fasting pose s major challenges to multiple sclerosis (MS) patients in Muslim countries. Physicians should have practical knowledge on the implications of fasting on MS. We present a summary of database searches (Cochrane Database of Systematic Reviews, PubMed) and a mini-symposium on Ramadan fasting and MS. In this symposium, we aimed to review the effect of fasting on MS and suggest practical guidelines on management. DISCUSSION: In general, fasting is possible for most stable patients. Appropriate amendment of drug regimens, careful monitoring of symptoms, as well as providing patients with available evidence on fasting and MS are important parts of management. Evidence from experimental studies suggests that calorie restriction before disease induction reduces inflammation and subsequent demyelination and attenuates disease severity. Fasting does not appear to have unfavorable effects on disease course in patients with mild disability (Expanded Disability Status Scale (EDSS) score ≤3). Most experts believed that during fasting (especially in summer), some MS symptoms (fatigue, fatigue perception, dizziness, spasticity, cognitive problems, weakness, vision, balance, gait) might worsen but return to normal levels during feasting. There was a general consensus that fasting is not safe for patients: on high doses of anti-convulsants, anti-spastics, and corticosteroids; with coagulopathy or active disease; during attacks; with EDSS score ≥7. SUMMARY: These data suggest that MS patients should have tailored care. Fasting in MS patients is a challenge that is directly associated with the spiritual belief of the patient.

Predictive ability of C-reactive protein for early mortality after ischemic stroke: comparison with NIHSS score.

We aimed to compare the association of high-sensitivity C-reactive protein (CRP) and National Institutes of Health Stroke Scale (NIHSS) score with mortality risk and to determine the optimal threshold of CRP for prediction of mortality in ischemic-stroke patients. A series of 162 patients with first-ever ischemic-stroke admitted within 24 h after onset of symptoms was enrolled. CRP and NIHSS score were estimated on admission and their predictive abilities for mortality at 7 days were determined by logistic-regression analyses. Receiver-Operating Characteristic (ROC) curves were depicted to identify the optimal cut-off of CRP, using the maximum Youden-index and the shortest-distance methods. Deceased patients had higher levels of CRP and NIHSS on admission (8.87 ± 7.11 vs. 2.20 ± 4.71 mg/l for CRP, and 17.31 ± 6.36 vs. 8.70 ± 4.85 U for NIHSS, respectively, P < 0.01). CRP and NIHSS were correlated with each other (r (2) = 0.39, P < 0.001) and were also independently associated with increased risk of mortality [odds ratios (95 % confidence interval) of 1.16 (1.05-1.28) and 1.20 (1.07-1.35) for CRP and NIHSS, respectively, P < 0.01]. The areas under the ROC curves of CRP and NIHSS for mortality were 0.82 and 0.84, respectively. The CRP value of 2.2 mg/l was identified as the optimal cut-off value for prediction of mortality within 7 days (sensitivity: 0.81, specificity: 0.80). Thus, CRP as an independent predictor of mortality following ischemic-stroke is comparable with NIHSS and the value of 2.2 mg/l yields the optimum sensitivity and specificity for mortality prediction.

Pharmacokinetic and pharmacodynamic properties of the new AEDs: A review article.

The new-AEDs, whose developments were motivated following the discovery of the valproate and its marketing in the U.S in 1978, have presented more therapeutic options. There are approximately twenty four FDA-approved antiepileptic drugs for use in patients with epilepsy, five of which were identified and have come on to the market between 2009 and 2012. The new-AEDs are of interest, not due to their efficacy, but rather owing to better tolerance, favorable pharmacokinetic profile, fewer interactions, and in some instances, lesser protein binding. No standard AED or those in developing have all properties of an ideal antiepileptic drug, thus to achieve desirable outcome, physicians should be aware of pharmacokinetics (PKs) and pharmacodynamics (PDs) of drugs. This review describes briefly the major features of the new AEDs.

The differential effects of OX1R and OX2R selective antagonists on morphine conditioned place preference in naïve versus morphine-dependent mice.

Conditioned place preference (CPP) has been associated with orexinergic (hypocrtinergic) system activation in naïve mice; however, the distinct role of different receptors of orexin in this paradigm has not been characterized yet. Moreover, the relationship between orexins and morphine in dependent mice may not be equal to naïve mice and seems noteworthy to investigate. We investigated the effects of systemic administration of orexin-1-receptor antagonist, SB 334867, and orexin-2 receptor antagonist, TCS-OX2-29 on the acquisition and expression of morphine conditioned place preference (CPP) in both naïve and morphine-dependent mice. We tested SB 334867 in three doses (10, 20 and 30 mg/kg), TCS-OX2-29 in two doses (5 and 10 mg/kg) and morphine with highest effective dose based on our dose-response experiment (5 mg/kg). Our results revealed that while SB 334867 suppressed CPP acquisition and expression in naïve mice, it failed to block CPP acquisition and expression in morphine dependent animals. In contrast, TCS-OX2-29 suppressed CPP acquisition and expression in both naïve and dependent mice significantly. The rewarding effect of morphine has stronger correlation with orexin-2 receptors in morphine-dependent mice while it depends on both kinds of receptors in naïve mice. This finding, if confirmed in other studies, persuades us to further investigate the role of orexin-2 receptor antagonists as potent drugs in addiction treatment.

A simple risk score for early ischemic stroke mortality derived from National Institutes of Health Stroke Scale: a discriminant analysis.

OBJECTIVES: The aim of the current study was to design a new simpler form of National Institutes of Health Stroke Scale (NIHSS) for use in emergency settings, and compare its predictive ability with original NIHSS score for mortality. METHODS: A total of 152 consecutive patients with first ever ischemic stroke admitted to a university affiliated hospital were recruited. NIHSS score on admission was estimated and the predictive ability of NIHSS items for mortality at 28 days was evaluated by logistic regression. Stepwise discriminant analysis was performed on NIHSS items to obtain a discriminant function with the best discriminative ability for mortality. Further, receiver operating characteristics (ROC) curves were depicted to compare the new determined discriminant function with the original NIHSS score. RESULTS: Cumulative rate of mortality was 11.8% for 28-day follow-up period. Among NIHSS items, scores of visual field, limb ataxia and extinction neglect were not associated with mortality (P>0.05). On the contrary, level of consciousness-commands, language and gaze were determined as independent indicators of mortality (P<0.05), and their coefficients on discriminant function were equal to 0.65, 0.44 and 0.30, respectively. In addition, area under the ROC curve of the calculated discriminant function was not statistically different from NIHSS score (P>0.05). CONCLUSIONS: The suggested discriminant function, comprising NIHSS items of level of consciousness-commands, language and gaze, can predict 28-day mortality after ischemic stroke in a similar way to the original NIHSS score and can provide a baseline for stroke severity in emergency settings.

Apolipoprotein E polymorphisms status in Iranian patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system. Evidences linking apolipoprotein E (APOE) to myelin repair, neuronal plasticity, and cerebral inflammatory processes suggest that it may be relevant in MS. The main goal of this study was to determine whether the APOE genotypes and alleles are associated with MS patients. MATERIALS AND METHODS: In total, 147 MS cases and 168 control subjects from Iranian population were genotyped for APOE gene using PCR-RFLP method. RESULTS: The frequency of APOE-ε2ε3 genotype was significantly higher in controls than cases (14.3% vs. 6.1%, P=0.009, OR=0.39) whereas APOE-ε3ε4 genotype frequency was significantly higher in cases compared with controls (8.2% vs. 3.6%, P=0.03, OR=2.4). APOE-ε2 allele frequency in cases was significantly lower than that of controls (4.4% vs. 8.0%, P=0.03, OR=0.52). Also male controls were significantly more likely to have APOE-ε2 allele (7.8% vs. 1%, P=0.01, OR=0.11). APOE-ε4 allele frequency in cases was significantly higher than control group (4.8% versus 2.1%, P=0.03, OR=2.35). CONCLUSION: It seems that individuals carrying APOE-ε4 allele and/or APOE-ε3ε4 genotype develop MS two times more than non-carriers. Also APOE-ε2ε3 genotype or APOE-ε2 allele may have a protective role against MS development in Iranian population. Further investigation would be warranted to understand the role of APOE alleles and genotypes and risk of MS.

Primary angiitis of the central nervous system.

Primary angiitis of the central nervous system (PACNS) is an idiopathic disorder (vasculitis) restricted to the central nervous system (CNS). It often presents with focal neurological deficits suggesting stroke or a combination of confusion and headache. We herein report three cases with various combinations of fever, partial seizure, encephalopathy, paresis, headache and ataxia. One of them was initially treated as herpes simplex meningoencephalitis, but further investigations revealed primary angiitis. Primary angiitis of the CNS has protean manifestations and should always be considered in patients suspicious to have CNS infection or stroke, particularly who does not respond to the routine treatments. Clinical data, exclusion of differential diagnoses and typical angiography seem to be enough to justify the diagnosis in the majority of cases.