Calcitriol, but not FGF23, increases in CSF and serum of MS patients.

The anti-inflammatory role of the active metabolite of vitamin D, namely 1, 25-dihydroxyvitamin D3 (calcitriol), has been reported in multiple sclerosis (MS). Moreover, recent studies have shown that fibroblast growth factor 23 (FGF23) is involved in the regulation of calcitriol biosynthesis. The probable changes of FGF23 and calcitriol concentrations in the CSF and serum of patients with MS were evaluated. Calcitriol concentration in the CSF and serum of MS patients was significantly higher than that in non-MS patients, while FGF23 concentration in MS patients was comparable to controls. We concluded that calcitriol concentration increases in the CSF and serum of MS patients independent of FGF23 status.

C/EBP homologous protein investigation in the serum and cerebro-spinal fluid of relapsing-remitting multiple sclerosis patients.

The exact determination of endoplasmic reticulum (ER) stress-associated proteins is not completely elucidated in the multiple sclerosis (MS) patients. We measured CHOP concentrations in the serum and cerebro-spinal fluid (CSF) of relapsing-remitting MS (RRMS) patients (n = 20) in comparison with the non-MS control group (n = 20) to determine whether this marker could be detected in the body fluids of RRMS patients. CHOP marker was not detectable in all harvested CSF samples. However, its levels were detectable in all serums harvested from both non-MS and RRMS patients and its levels in the latter group were not significantly higher than those of the non-MS control group (P value = 0.265). CHOP was not detectable in the CSF of RRMS patients in spite of the recent reports on the RRMS autopsies. Additionally, there were not any significant correlations (Spearman's correlation) between both of EDSS score and age with CHOP serum concentrations in all subjects.

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.

Soluble CD40 ligand derived from serum is not correlated with early MS.

BACKGROUND: Soluble CD40 ligand (sCD154) is a proinflammatory and prothrombotic ligand belonging to the tumor necrosis factor family. It has been shown by a variety of studies that sCD154 is elevated in the serum of patients afflicted with system autoimmune diseases. The aim of our study was to address whether sCD154 is increased in disease affected by Multiple Sclerosis (MS). METHODS: Twenty MS patients who have been newly diagnosed as clinically definite multiple sclerosis (CDMS) along with twenty age and sex matched healthy individuals were recruited for this study. Serum cCD154 was measured by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: The results showed no statistically meaningful difference between newly diagnosed MS patients (3.07ng/ul±0.66) and control group (2.95ng/ul±0.79; p=0.62) CONCLUSION: Regarding our study, it seems that soluble CD40 ligand derived from serum is not correlated with early stage of MS disease.

Multiple sclerosis influences on the augmentation of serum Klotho concentration.

We have already shown that the concentration of secreted form of Klotho decreases in the cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis (RRMS). The current study aimed at assessing possible changes in the serum Klotho concentration of MS patients. Participants involved 15 new cases of RRMS patients in the relapse phase, 15 RRMS patients who had been suffering from the disease for more than three years and were under regular treatments (interferon beta-1a) and, finally, 15 non-MS patients who constituted the control group. Beside thorough neurological examinations, demographic and clinical data (e.g. gender, age, duration of disease and expanded disability status scale) were obtained. Serum Klotho concentration was measured using ELISA method. The results showed no statistically meaningful difference between new cases of RRMS (585.56pg/ml±153.99) and control group (556.81pg/ml±120.36; P=0.859). The serum Klotho level, however, was significantly higher in patients with prolonged disease duration (696.94pg/ml±170.52; P=0.037) in comparison with the subjects in the control group. In conclusion, this study showed that serum Klotho concentration tends to be higher in MS patients when compared to control group. This finding might be attributed to treatment of MS patients with immunomodulatory drugs or a compensatory response to enhance CNS regeneration and/or vitamin D biosynthesis. Further studies are required to elucidate the role of Klotho in MS pathophysiology.

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.

Decreased concentration of Klotho in the cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis.

Recent investigations support that an anti-aging protein, namely Klotho, protects neurons against the oxidative stress and demyelination. We evaluated the protein concentration of Klotho and total anti-oxidant capacity (TAC) in the cerebrospinal fluid (CSF) of patients with relapsing-remitting multiple sclerosis (RRMS). Klotho concentration and TAC were significantly lower in patients as compared to controls. Klotho values showed a significant negative correlation with expanded disability status scale (EDSS). Moreover, a significantly positive correlation between TAC levels and Klotho concentrations was detected. Klotho may play an important role in the pathogenesis of MS, at least in part, through the regulation of redox system.

Impact of Melatonin on Motor, Cognitive and Neuroimaging Indices in Patients with Multiple Sclerosis.

A series of preclinical and clinical studies have shown the immunomodulatory effect of  melatonin, especially in the state of chronic inflammation. A double-blind, randomized, parallel-group, placebo-controlled clinical trial was designed to study the tolerability and efficacy of supplemental therapy with melatonin (3 mg/day) in comparison to placebo in relapsing-remitting MS (RRMS) patients receiving once weekly interferon beta. Patients were followed up for 12 months. Primary outcomes consisted of the number of relapses, change in Extended Disability Status Scale (EDSS), and the number and volume of new T2 and gadolinium-enhancing brain lesions. Secondary outcomes included change in performance on Multiple Sclerosis Functional Composite (MSFC) as well as change in fatigue and depression. The outcomes were evaluated every three months. Twenty-six patients (13 in each group) were recruited in the study. All participants, except for one patient in the placebo group, completed the study. No patient reported serious adverse events. There was no significant difference either in primary or secondary outcomes between melatonin and placebo arm. However, a trend for beneficial effect was observed for melatonin on change in MSFC performance and the cognitive subscore of the Modified Fatigue Impact Scale (p=0.05 and 0.006, respectively, not corrected for multiple comparisons). We found no significant effect for treatment with melatonin on measures of clinical and functional disability and development of brain lesions in our small sample-size study. Studies with higher statistical power and longer follow up are needed to further evaluate the potential immunomodulatory effect of melatonin in RRMS treatment.

Decreased urinary level of melatonin as a marker of disease severity in patients with multiple sclerosis.

Melatonin has both pro-inflammatory and anti-inflammatory properties depending on the stage of inflammation. Despite its therapeutic effect in alleviation of some symptoms of multiple sclerosis; the precise role of melatonin in MS pathogenesis remains a topic of debate. The aim of this study was to measure the urine level of one of melatonin products which is an index of serum melatonin level, in MS patients in the acute phase of relapse and control patients. We also analyzed different clinical and cognitive indices in order to find any correlation with melatonin level. Twenty eight patients who were diagnosed as relapsing-remitting MS, according to the revised McDonald criteria, along with 10 age- and sex-matched control subjects were recruited in our study. Here we showed that urine 6-sulphatoxymelatonin levels (aMT6s; the major metabolite of melatonin) were significantly lower in MS patients compared to control group. Interestingly, urine aMT6s levels significantly correlated with MS Functional Composite score, but not Expanded Disability Severity Score. Based on above findings, there might be new hope in developing a quantitative and objective measure to assess the MS severity especially in neurodegenerative diseases. However, our results should be analyzed cautiously. We didn't evaluate simultaneous level of 25-OH Vitamin D. It has been recently reported that there is a negative correlation between melatonin and vitamin D levels. Further studies are needed to confirm this hypothesis.

Multiple sclerosis and pregnancy; What a neurologist may be asked for?

Multiple sclerosis (MS) is the most common chronic autoimmune demyelinating disorder of the central nervous system (CNS) which preferentially involves young women in early child bearing age. Opposite to traditional view emphasized on discouraging female patients from enduring pregnancy, recent investigations showed that pregnancy-related physiological alterations, especially during the third trimester, reduce the annual relapse rate of multiple sclerosis up to 80% which is comparable with conventional disease modifying drugs. Nowadays, expert's viewpoint is that female patients should not be discouraged from having children. Nonetheless, who and when should be allowed to endure gestational period is a complex decision which should be taken for every patient individually. It necessitates that neurologists be aware of updated information regarding pregnancy-related fetal and maternal considerations in patients with MS. In this brief review, it was tried to discuss this topic according to available data and guideline-based recommendations.

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.

Relationship between HLA-DRB1* 11/15 genotype and susceptibility to multiple sclerosis in Iran.

BACKGROUND & OBJECTIVES: Analysis of the role of different alleles of human leukocyte antigen (HLA) in multiple sclerosis (MS) patients is necessary in many populations and geographical areas. The aim of the present study was to investigate the frequency of HLA-DRB1 genes and its influence on susceptibility to MS, comparing with that in control group. DESIGN AND SETTING: Two groups of case-control of multiple sclerosis patients referred to clinic at Khatam hospitals were studied. The first group consisted of 73 multiple sclerosis patients and the second group comprised 40 healthy volunteers with no known history of MS, living in Tehran. PATIENTS AND METHODS: The sample population consisted of 73 consecutive non-selected patients diagnosed with MS according to the McDonald criteria (2010) at the outpatient clinic for multiple sclerosis, 62 (85%) presented with RRMS and 11 (15%) with SPMS. The frequency of HLA-DRB1 alleles was determined in 73 MS patients (with age of 18-56) and 40 healthy subjects in Iran. These consisted of 57 females and 16 males. HLA-DRB1 allele types were identified by polymerase chain reaction products of 24 pair primers for low resolution SSP typing (PCR-SSP). RESULTS: The HLA-DRB1* 11/15 genotype was detected highest (6 times) in patients compare to normal control population (p-value 0.062), whereas the DRB1 4/11 genotype was detected highest (4 times) in controls compare to MS patients (p-value 0.033). The data showed that HLA-DRB1*03 is significantly more in patients compare to control normal people (p-value 0.0021) as well as DRB1 14 and 16 are significantly more in control normal people, compare to MS patients (p-values 0.0789 and 0.035). CONCLUSION: Allele frequency among patients with positive history of multiple sclerosis disease showed that DRB1 11 allele has a significantly low rate in MS patients with positive history compare to other patients. In contrast DRB1 15 allele has a significantly high rate in MS patients with positive history compare to other patients. The frequencies of other alleles were not significantly different between the MS patients and the control group. The frequency of the HLA-DRB1* 11/15 genotype detected in the present study showed that this genotype is partially significant factor for MS susceptibility and development in Iran.

Increased autotaxin activity in multiple sclerosis.

Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA) from lysophosphatidyl choline (LPC) and it is up-regulated in inflammatory conditions such as various cancers, arthritis and multiple sclerosis (MS). Numerous studies have shown that the LPA signaling gives rise to angiogenesis, mitosis, cell proliferation and cytokine secretion. On the one hand, an increasing body of evidence suggests that blockade of ATX has anti-inflammatory properties in a variety of diseases. The aim of this study was to measure the enzyme activity of ATX in cerebrospinal fluid (CSF) and serum of patients with MS using an enzymatic photometric method. Twenty definite relapsing remitting MS patients along with 20 patients with other neurological diseases (OND) were recruited. The results showed that ATX activity was significantly higher (p value<0.0001) in MS patients than those patients diagnosed with OND. It is possible that inhibition of the ATX may decrease the rate of MS relapses/progression.

Hashimoto Encephalopathy in Case of Progressive Cognitive Impairment; a Case Report.

Hashimoto's encephalopathy (HE) is a rare condition characterized by atypical psychiatric and heterogeneous neurological manifestations such as acute cerebral ischemia, seizure, tremors, myoclonus, psychosis, depression, cognitive disorders, and fluctuating loss of consciousness. Here, a case of 28 year-old man was reported who referred to the emergency department (ED) with different acute neurologic disorders and final diagnose of HE.

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.

Secretory phospholipase A2 activity in serum and cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis.

An increasing body of evidence suggests that patients afflicted with multiple sclerosis (MS) show alterations in immunologic markers including increases in proinflammatory cytokine activity and inflammation. Secretory Phospholipase A2 (sPLA2) is one of the key molecules contributing to the production of inflammatory lipid mediators, mainly eicosanoids. They are considered proinflammatory enzymes and their inhibition has long been recognized as a desirable therapeutic target. The aim of this study was to measure the enzyme activity of sPLA2 both in serum and cerebrospinal fluid (CSF) of MS patients. Twenty MS patients accompanied with 20 age-sex matched controls were recruited. The results showed that the enzyme activity of serum sPLA2 was 0.007±0.021 (µmol/min/ml) in MS patients vs. 0.007±0.016 (µmol/min/ml) in patients with other neurological diseases as a control group (P=0.5). Our findings also indicated that there is no correlation (P=0.6) between CSF sPLA2 enzyme activity and MS disease when the results of two groups were compared (0.072±0.020 in cases vs. 0.071±0.01 in control group). The results suggest that the enzyme activity of sPLA2 is not altered during the disease course.