Matrix metalloproteinases and their tissue inhibitors in relapsing remitting multiple sclerosis: Possible markers and treatment agents.

BACKGROUND AND PURPOSE: Matrix metalloproteinases (MMPs), which are synthesized by many cell groups and responsible for the destruction of matrix proteins, and endogen tissue inhibitors of MMPs (TIMPs) have a role in the pathogenesis of Multiple Sclerosis (MS) by affecting the blood-brain barrier. We aimed to investigate the role of MMPs and TIMPs in the immunopathogenesis and in the course of multiple sclerosis (MS). METHODS: We enrolled 25 relapsing remitting MS patients, who had a definite MS diagnosis according to McDonald criteria and 25 healthy subjects similar for age and gender as control group. MMP-9- and TIMP-1 levels were measured twice in patient group (one time during an attack and one in remission) and once in healthy subjects. RESULTS: MMP-9- and TIMP-levels of patients during attack and remission period and MMP-9/TIMP-1 ratio were found significantly higher than in the control subjects. In patient group MMP-9 and TIMP-1 levels and MMP-9/TIMP-1 ratio during attacks were not significantly different than during remission period. However, when subdivided according to their number of attacks, patients with 2 attacks had significantly higher levels during attack period comparing to remission period (p<0.05); in case of patients with more than 2 attacks did not have a statistically significant difference in attack and remission periods. CONCLUSION: Matrix metalloproteinases are important actors in MS immunopathogenesis, particularly in the early period and inhibitor agents for these enzymes can be used as a treatment option.

Plasma copeptin levels in patients with multiple sclerosis.

We compared copeptin levels in relapsing-remitting multiple sclerosis (RRMS) patients with controls and investigated how plasma copeptin levels were changed with the disease period. Thirty patients with RRMS without a prior attack in the last twelve months, and 19 RRMS patients with a clinical acute attack and 30 healthy individuals were included into the study. Copeptin levels were significantly higher in all RRMS patient groups than healthy controls. Plasma copeptin levels were higher in patients in remission period compared with relapse period of 19 RRMS patients with an acute attack. We consider copeptin can be used as a potential biomarker for RRMS.

Orexin/hypocretin receptor, Orx1, gene variants are associated with major depressive disorder.

Objective: Orexins (hypocretins) are neuropeptides expressed in hypothalamic neurons and have regulatory roles in feeding/drinking behaviours, endocrine functions and sleep/wakefulness state. Major depressive disorder (MDD) is a major mood disorder and neurotransmitter dysfunction in hypothalamic neurons may have roles in its formation. Hence, we conducted experiments to determine whether orexin receptor 1 and 2 (Orx1, Orx2) genes were associated with MDD development. Methods: Seventy-five MDD patients and 87 healthy controls were enrolled for the study. Genotyping was carried out with real-time polymerase chain reaction (RT-PCR). Hamilton Rating-Scale for Depression (HRSD) and Beck Depression Inventory (BDI) were utilized to evaluate depressive symptom severity. Results: A significant relation was found in genotype frequencies of Orx1 rs10914456 and rs2271933 variants between MDD patients and controls (p = .009, p = .006). Rs10914456 CC genotype increased MDD risk 3.57 times more than carrying other genotypes (p = .008, OR =3.57;95% CI: 1.39-9.14). However, no association was observed in Orx2 rs2653349 genotypes for MDD development (p > .05). Although statistically not significant, HRSD scores were diminished in MDD subjects carrying rs10914456 CC variants when compared with CT and TT variants (p = .069). Conclusion. This study suggests that, Orx1 rs10914456 and rs2271933 can be associated with MDD development. Hence, Orx1 rs10914456 variants may affect depressive symptom severity.

Anti-Neuronal Autoantibodies in Both Drug Responsive and Resistant Focal Seizures with Unknown Cause.

BACKGROUND: and Objective Autoimmunity is an emerging field of research in the etiology of different neurological disorders including epilepsy. We aimed to investigate the presence of neuronal autoantibodies in focal epilepsy with unknown cause and their clinical correlates in both drug-responsive and resistant patients. METHOD: Between 2009 and 2010 94 patients were prospectively enrolled, had their antibodies tested and clinically followed." An additional 50 age- and gender-matched controls were also tested for antibodies. Age at examination, gender, age at onset, seizure frequency, risk factors, seizure precipitants, and type of seizures were noted. Plasma obtained from patients was frozen at -80°C and analysed for autoantibodies against VGKC-complex, VGCC, GAD, LGI1, CASPR2, NMDA, AMPA and GABAB receptors with immunocytochemistry and radioimmunoassay as required. RESULTS: Thirteen (13.8%) patients, but none of the controls, had antibodies (p=0.003). Antibodies were directed against the uncharacterized components of VGKC-complex in 5 patients (5.3%), GAD in 4 patients (4.2%), NMDA-R in 1 patient (1%), AMPA-R in 1 patient (1%) and both GAD and VGKC-complex in 2 patients (2.1%). Prognosis of epilepsy, in subsequent follow-up, did not correlate to general presence of anti-neuronal antibodies with slightly more patients with antibodies epilepsy control than without (76.9% vs. 69.1%, not-statistically significant. Three patients with suspected active autoimmunity and epilepsy who were treated, showed a response to treatment with a reduction in the seizure frequency. Although most clinical features were identical between seropositive and seronegative patient groups, seropositive patients were more likely to have inflammatory/autoimmune disorders in their medical history. DISCUSSION: In keeping with previous studies, we have shown anti-neuronal antibodies in a proportion of focal epilepsy patients. Although autoimmunity might merely occur as a bystander effect in many chronic neurological disorders, association of anti-neuronal antibodies with good response to immunotherapy and coexisting autoimmune disorders suggests that anti-neuronal autoimmunity might participate in seizure formation at least in a subgroup of focal epilepsy patients. CONCLUSION: Immunity may play a role in some patients with unknown etiology regardless of prognosis and immunmodulatuar treatment may be helpful in seropositive group.

Sciatic neuropathy developed after injection during curettage.

Intramuscular injections are likely the most common cause of sciatic nerve injury in developing countries. Less common causes include piriformis syndrome, primary tumors of the sciatic nerve, metastatic tumors invading or compressing the nerve, endometriosis, vascular malformations, and prolonged immobilization or positioning. While the most reliable diagnostic and prognostic methods include nerve conduction studies and electromyography, magnetic resonance imaging has been suggested as an alternative method of determining type of lesion, establishing location, and investigating level of nerve involvement. A case of sciatic neuropathy that developed after intramuscular injection, with patient in prolonged lithotomy position and under sedation, is described.

Pregnancy Data in a Turkish Multiple Sclerosis Population.

BACKGROUND: To conduct the first retrospective clinical study investigating pregnancy in Turkish multiple sclerosis (MS) patients. SUMMARY: We evaluated 558 pregnancies in 199 MS patients and results were compared with general Turkish population's data. The fertility rate in the MS group was found to be lower than that in the general population, even before MS diagnosis was established. Our study suggests that the higher number of pregnancies may have a favorable effect on transition from relapsing-remitting MS to secondary progressive MS, although no effect has been shown regarding the possibility to reach EDSS 6.0 as a milestone. KEY MESSAGES: Our data support the conclusion that MS does not have a negative effect on the MS course and disability.

Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorder Patients in Turkish Cohort: Demographic, Clinical, and Laboratory Features.

BACKGROUND: Neuromyelitis optica (NMO) is an immune-mediated, chronic relapsing, inflammatory disease characterized by severe attacks of optic neuritis and myelitis. OBJECTIVE: To determine the demographic, clinical, and laboratory features; antibody status; and treatment modalities of patients with NMO and neuromyelitis optica spectrum disorders in a Turkish cohort from 11 centers. METHODS: A total of 182 patients were included in this study. Data on age at disease onset, sex, type of attacks, clinical presentation, analysis of cerebrospinal fluid, serum antiaquaporin-4 antibody status, annual progression index, and medical and family histories were collected. RESULTS: Mean age was 38.43±12.40 years (range, 13 to 75 y), and mean age at disease onset was 31.29±12.40 years (median, 29 y; range, 10 to 74 y). In NMO group, the rate of NMO immunoglobulin (Ig)G positivity was 62.5%. The annual progression index was significantly higher in the longitudinally extending spinal cord lesion. The mean Expanded Disability Status Scale score was higher in the late than early-onset NMO group. CONCLUSION: Our results revealed a lower rate of NMO IgG positivity, more severe disability in patients with NMO/neuromyelitis optica spectrum disorders presenting with either transverse myelitis or late-onset NMO, and no correlation between disability and NMO IgG status.

Diagnosis and Treatment in Neurosarcoidosis.

Sarcoidosis is an inflammatory multisystem disorder, affecting many systems such as lung, lymph nodes, skin and eye involvement. Nervous system involvement is often seen in 5-15% of patients with systemic sarcoidosis in the first two years. Preceding to systemic involvement the initial symptom as neurological complaints has been rarely reported. Lacking of any specific, clinical and / or radiological findings for neurosarcoidosis in these cases, it could be difficult to make an accurate diagnosis and histopathological evaluation may be required. Due to rarity and complexity diagnosis of the neurosarcoidosis, in this study, clinical, radiological and / or histopathological features, treatment modalities of the 7 neurosarcoidosis patients to be presented with detailed investigations of different neurological symptoms were evaluated.

Should HAS-BLED scoring be revised for better risk estimation in patients with intracerebral hemorrhage?

Many efforts have been made to develop decision-support tools and bleeding prediction schemes to start or resume anticoagulation after intracerebral hemorrhage, related with anticoagulation use or not, such as CHA2DS2-VASc or HAS-BLED scoring. HAS-BLED is a validated scoring system to predict the risk of major bleeding in a patient with atrial fibrillation; some current scientific guidelines suggest its use in 'risk-benefit' reasoning when deciding whether to start long-term oral anticoagulation. Here the authors present a patient with atrial fibrillation and intracerebral hemorrhage, and aim to discuss the use of HAS-BLED, suggesting that some revisions may help better management of these patients for major bleeding risk.

The prevalence of migraine in restless legs syndrome.

OBJECTIVE: While previous studies have investigated the prevalence of restless legs syndrome (RLS) in patients with migraine, we aimed to explore the prevalence and characteristics of migraine in adult patients diagnosed with RLS. BACKGROUNDS: The association of primary headaches, especially of migraine, with RLS has recently attracted much attention. Migraine prevalence was reported to be higher in patients with RLS than in the general population, and the role of dopamine was strengthened. METHODS: We evaluated 265 consecutive adult RLS patients (137 males and 128 females) followed up in a Sleep Disorders Unit and diagnosed according to criteria defined by the International Restless Legs Syndrome Study Group (IRLSSG). RLS characteristics, and the severity, were performed by using the IRLSSG severity scale. The diagnosis of headache subtypes was defined by the International Classification of Headache Disorders. Gender, age, age at RLS onset, duration of RLS, family history of RLS, family history of headache, presence of depression, any treatments given for RLS, and the change in headache following RLS treatment were questioned. RESULTS: The mean age of the study population was 50.4 ± 12.8 years, mean age at RLS onset was 41.6 ± 13.2 years, and mean disease duration was 8.40 ± 8.6 years. Of these, 163 patients had headache; 40 of them were diagnosed to have migraine-type headache (15.1%). The presence of migraine-type headache was 9.4% in males with RLS, and 21.1% in female RLS patients. In RLS patients with migraine, 67.5% were females, while 48.0% of RLS patients with other types of headache were females (P = .032), and only 41.2% of RLS patients without headache were females (P = .005). The severity of RLS was significantly higher in patients with migraine compared with those without headache (P < .001). The presence of depression, the family history of RLS, and headache were also higher in patients with migraine compared with RLS patients with other types of headache or those without headache. Thirty-six patients with headache reported partial or substantial benefit from RLS treatment. CONCLUSIONS: Our results did not suggest higher rates of migraine-type headache in RLS patients when compared with population-based prevalence studies from Turkey. Alternatively, the severity of RLS was significantly higher in patients with migraine. Although the increase in these scores does not constitute a relationship etiopathogenetic, it suggests a correlation between the type cross-model nociceptive systems. Moreover, the family history of RLS was higher in patients with migraine. The prevalence of migraine in patients with RLS, however, waits to be better demonstrated.

CAP characteristics differ in patients with arousal parasomnias and frontal and temporal epilepsies.

Arousal parasomnias (AP) and frontal and temporal epilepsies consist of pathologic arousals originating in abnormal thalamocortical circuits, reflecting increased sleep instability and arousal oscillations--the cyclic alternating pattern (CAP). In this study, the authors aim to investigate the CAP characteristics in 27 patients with AP, 22 patients with frontal and temporal epilepsies, and age- and gender-matched 20 healthy subjects. The mean CAP sequence and cycle was significantly higher in patients than in control subjects (P < 0.003). The total CAP duration was always higher in the patients with AP than in those with frontal and temporal epilepsies, reaching statistically significant level at the first (P = 0.044), second (P = 0.024), third (P = 0.010), and sixth (P < 0.001) sleep cycles. The duration of A1 in descending branch (P = 0.062) and trough phase of sleep cycles (P = 0.038) was longer in the patients with AP. The duration of A2 subtype of CAP in ascending branch (P = 0.039) and the number (P = 0.036) and duration (P = 0.050) of A3 subtype of CAP in descending branch of sleep cycles were higher in the patients with frontal and temporal epilepsies. This difference in CAP parameters might suggest that AP are associated with milder activation in specific brain areas, showing a similar evolution with physiologic homeostatic decrease in sleep synchronization. Frontal and temporal epilepsies, however, is associated with a moderate-to-powerful activation in wider brain networks.