Two New Cases and Literature Review of CLIPPERS Syndrome with Long-Term Follow-up.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder of the central nervous system. The pathophysiology of CLIPPERS is unknown. The disease has characteristic radiological lesions located in the pons, bulbus, and cerebellum. Here we report two new cases and review the literature on CLIPPERS syndrome. A 35-year-old woman presented with a 2-month history of progressive double vision, vertigo, gait ataxia, nausea, and vomiting. The second case was that of a 40-year-old Iraqi man who presented with a 3-month history of vertigo, headache, and gait ataxia. Diagnosis of CLIPPERS was established based on findings of punctate, nodular enhancing lesions in the pons and bulbus in the first case and in the cerebellum in the second. Our patients responded well to steroid therapy and remained relapse-free for 2 years. CLIPPERS is a rare autoimmune disorder with characteristic radiological findings. Long-term immunosuppressive therapy is necessary for treatment.

Differences Between General Neurologists and Multiple Sclerosis Specialists in the Management of Multiple Sclerosis Patients: A National Survey.

INTRODUCTION: The management of multiple sclerosis (MS) has become more complicated after the introduction of new diagnostic and treatment options. Despite the abundance of guidelines, the experience of physicians still plays a major role in the management of patients. This study aimed to define differences in behavior patterns between general neurologists (GNs) and MS specialists (MSSs). METHODS: We conducted a survey of 36 questions to 318 neurologists, including 33 MSSs. The survey covered topics including laboratory investigations, pregnancy, and treatment. RESULTS: Our study found many differences between GNs and MSSs in terms of management, the most important being treatment initiation and switching. GNs had a tendency to initiate treatment later than MSSs however, they tended to switch treatment faster. Our study also showed that GNs ordered magnetic resonance imaging (MRI) more frequently than MSSs, even if patients were clinically stable. Moreover, although GNs more frequently relied on MRI, they did not consider brain atrophy as an important measure in the follow-up of their patients. Furthermore, GNs considered replacement therapy less often than MSSs, even in patients with vitamin D deficiency. DISCUSSION: Our study revealed important discrepancies between the management patterns of GNs and MSSs in MS patients. These findings suggest the need for a national education program for GNs on MSSs.

Listeria monocytogenes rhombencephalitis in a patient with multiple sclerosis during fingolimod therapy.

OBJECTIVE: To describe a case of Listeria monocytogenes rhombencephalitis in a patient receiving fingolimod. METHODS: This is a case study. RESULTS: Our patient developed acute rhombencephalitis with hydrocephalus induced with Listeria monocytogenes while on fingolimod. Shunt surgery was performed for the hydrocephalus and patient recovered partially after medical and surgical therapy. CONCLUSION: We describe the first probable case of fingolimod-associated Listeria monocytogenes rhombencephalitis in a patient with multiple sclerosis. Clinicians should be aware of listeriosis and implement measures for its prevention.

Does Psychodrama Affect Perceived Stress, Anxiety-Depression Scores and Saliva Cortisol in Patients with Depression?

OBJECTIVE: Little is known about the effects of psychodrama group therapy on the level of stress, anxiety and depression of the group members, and the biological markers of stress. The aim of this study test cortisol level as a biological reflection of some mental characteristics gained by the psychodrama method in coping with stress. METHODS: Depressive patients aged between 18 and 65 years, who diagnosed with depression according to DSM-5, without psychiatric comorbidity, who do not use drugs and were available for psychodrama were enrolled into the study. These patients were evaluated using the Perceived Stress Scale, State-Trait Anxiety Inventory and Beck Depression Inventory. In order to observe the circadian rhythm of cortisol, samples were collected from the participants before lunch, before dinner and before going to sleep on the day before psychodrama and on the 0, 15th, and 30th minutes after awakening in the morning of the psychodrama day; as well as just before and after the psychodrama session. Saliva cortisol level just before the initial session of psychodrama group therapy was compared with the saliva cortisol level just after the last psychodrama session at the end of 16 weeks. RESULTS: Statistically significant difference was determined between the scores of perceived stress scale, STAI-1, STAI-2, beck depression inventory and salivary cortisol level before and after psychodrama session. There was significant decrease in both the scale scores and salivary cortisol after vs. before psychodrama. CONCLUSION: This results is important as it shows the biological aspect of clinical improvement. Further studies would provide us with better understanding of the effects of psychodrama group psychotherapy on depressive mood and biological projections by means of short-term and long-term follow-up studies.

The beneficial effects of 18ß-glycyrrhetinic acid on the experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mouse model.

AIM: The aim of this study was to investigate the beneficial effects of 18ß-glycyrrhetinic acid (GA) on the experimental allergic encephalomyelitis (EAE) in C57BL/6 mice. GA is a natural substance found in the root of licorice and is used in traditional Chinese medicine. It has many pharmacological activities such as antioxidant, anti-inflammatory, and anti-cancer effects. MATERIALS AND METHODS: A total of 40 C57BL/6 mice were divided equally into four groups: (1) Control, (2) EAE, (3) GA and (4) GA + EAE. 14 days after induction of EAE with MOG35-55 and pertussis toxin, mice were treated with GA at doses of 100 mg/kg/day for 7 days intraperitoneally. RESULTS: To our results, oxidative stress and lipid peroxidations (elevated TBARS levels, decreased GPx, SOD, CAT, and GSH levels) were significantly (p < .01) increased, causing EAE in brain tissue. Also, histopathological damage (Caspase-3 and IL-17 activity, p ≤ .01) and cytokine levels (TNF-α and IL-1ß, p < .01) were induced with EAE in mice brain tissue. On the other hand, GA treatment significantly (p < .01) reversed oxidative histological and immunological alterations caused by EAE. CONCLUSIONS: In conclusion, the GA treatment can protect the brain tissue against EAE in mice with its antioxidant and anti-inflammatory properties.

Neurological autoantibodies in drug-resistant epilepsy of unknown cause.

BACKGROUND: Autoimmune epilepsy is a rarely diagnosed condition. Recognition of the underlying autoimmune condition is important, as these patients can be resistant to antiepileptic drugs. AIMS: To determine the autoimmune and oncological antibodies in adult drug-resistant epilepsy of unknown cause and identify the clinical, radiological, and EEG findings associated with these antibodies according to data in the literature. METHODS: Eighty-two patients with drug-resistant epilepsy of unknown cause were prospectively identified. Clinical features were recorded. The levels of anti-voltage-gated potassium channel complex (anti-VGKCc), anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody (ANA), anti-glutamic acid decarboxylase (anti-GAD), anti-phospholipid IgG and IgM, anti-cardiolipin IgG and IgM, and onconeural antibodies were determined. RESULTS: Serum antibody positivity suggesting the potential role of autoimmunity in the aetiology was present in 17 patients with resistant epilepsy (22.0%). Multiple antibodies were found in two patients (2.6%). One of these patients (1.3%) had anti-VGKCc and ANA, whereas another (1.3%) had anti-VGKCc and anti-TPO. A single antibody was present in 15 patients (19.5%). Of the 77 patients finally included in the study, 4 had anti-TPO (5.2%), 1 had anti-GAD (1.3%), 4 had anti-VGKCc (5.2%) 8 had ANA (10.3%), and 2 had onconeural antibodies (2.6%) (1 patient had anti-Yo and 1 had anti-MA2/TA). The other antibodies investigated were not detected. EEG abnormality (focal), focal seizure incidence, and frequent seizures were more common in antibody-positive patients. CONCLUSION: Autoimmune factors may be aetiologically relevant in patients with drug-resistant epilepsy of unknown cause, especially if focal seizures are present together with focal EEG abnormality and frequent seizures.

Analysis of Vitamin D Receptor Polymorphisms in Patients with Familial Multiple Sclerosis.

OBJECTIVE: Genetic and environmental factors are important in the development of the multiple sclerosis (MS). Vitamin D shows its effects on the immune system with the vitamin D receptor (VDR) in the nucleus. Single nucleotide polymorphisms (SNPs) in the VDR gene can lead to alterations in vitamin D functions and metabolism.Taq I, Apa I, Fok I and Bsm I polymorphisms and MS associations have been investigated in many studies. VDR gene polymorphism has not been previously studied in patients with familial MS. AIM: We aimed to investigate the relationship between familial MS patients present in Turkish population and VDR genotypes Taq I, Apa I and Fok I polymorphisms. METHODS: 29 patients with a family history of MS and 120 healthy control subjects were included in the present study. We studied present VDR genotypes Taq I, Apa I and Fok I polymorphisms. RESULTS: We observed a significant difference between controls and patient group only in Taq I polymorphism (p: 0.025). Homozygousity of G allele was not seen in the patients whereas in controls frequency of that genotype was p:0.208. When gender was considered males show significant difference for GG genotype. There were no significant association for the Apa I and Fok I polymorphisms. CONCLUSION: Although our findings suggest association between VDR Taq I polymorphism and the familial MS, additional studies are needed to establish detailed relationships.

Cerebrospinal Fluid Dynamics in Patients with Multiple Sclerosis: The Role of Phase-Contrast MRI in the Differential Diagnosis of Active and Chronic Disease.

Objective: Multiple sclerosis (MS) is an inflammatory disease characterized by demyelinating plaques in the white matter. Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed as a new hypothesis for the etiopathogenesis of MS disease. MS-CCSVI includes a significant decrease of cerebrospinal fluid (CSF) flow through the cerebral aqueduct secondary to an impaired venous outflow from the central nervous system. This study aimed to determine whether CSF flow dynamics are affected in MS patients and the contributions to differential diagnosis in active and chronic disease using phase-contrast magnetic resonance imaging (PC-MRI). Materials and Methods: We studied 16 MS patients with chronic plaques (group 1), 16 MS patients with active plaques-enhanced on MRI (group 2), and 16 healthy controls (group 3). Quantitatively evaluation of the CSF flow was performed from the level of the cerebral aqueduct by PC-MRI. According to heart rates, 14-30 images were obtained in a cardiac cycle. Cardiac triggering was performed prospectively using finger plethysmography. Results: No statistically significant difference was found between the groups regarding average velocity, net forward volume and the average flow (p > 0.05). Compared with the controls, group 1 and group 2, showed a higher peak velocity (5.5 ± 1.4, 4.9 ± 1.0, and 4.3 ± 1.3 cm/sec, respectively; p = 0.040), aqueductal area (5.0 ± 1.3, 4.1 ± 1.5, and 3.1 ± 1.2 mm2, respectively; p = 0.002), forward volume (0.039 ± 0.016, 0.031 ± 0.013, and 0.021 ± 0.010 mL, respectively; p = 0.002) and reverse volume (0.027 ± 0.016, 0.018 ± 0.009, and 0.012 ± 0.006 mL, respectively; p = 0.000). There were no statistical significance between the MS patients with chronic plaques and active plaques except for reverse volume. The MS patients with chronic plaques showed a significantly higher reverse volume (p = 0.000). Conclusion: This study indicated that CSF flow is affected in MS patients, contrary to the hypothesis that CCSVI-induced CSF flow decreases in MS patients. These findings may be explained by atrophy-dependent ventricular dilatation, which may occur at every stage of MS.

The association between vitamin D receptor polymorphisms and multiple sclerosis in a Turkish population.

BACKGROUND: Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS). Genetic and environmental factors are important in disease development. Many studies have investigated the relationship between MS and VDR polymorphisms. VDR gene polymorphism has not been previously studied in Turkish MS patients. We aimed to investigate the relationship between MS and VDR genotypes Taq I, Apa I and Fok I polymorphisms in a Turkish population. METHODS: 167 MS patients and 146 healthy control subjects were included in the present study. MS and the VDR TaqI (rs731236), ApaI (rs7975232), and FokI (rs2228570) polymorphisms were investigated. RESULTS: The study enrolled 167 patients (121 females, 46 males) with MS and 146 healthy individuals (88 females, 58 males). The frequency of only the Fok I polymorphism differed significantly between the two groups (p = 0.002). The TaqI (rs731236) and ApaI (rs7975232) genotype distributions were not significantly different between MS patients and healthy controls (p = 0.626 and p = 0.990, respectively). Also there were no significant gender difference between patients and controls for Taq I and Apa I. CONCLUSION: In conclusion, we found a significant association between MS and the FokI polymorphism in our region of Turkey. However, the results may be different in other populations. More epidemiological and genetic studies are needed to explain the association between genetic factors and MS.

A Rare Presentation of Cranial Polyneuropathy Without Rash Caused by Varicella Zoster Virus.

INTRODUCTION: Varicella Zoster Virus (VZV) is associated with many disorders of the central and peripheral nervous systems including neuralgia, meningitis, meningoencephalitis, cerebellitis, vasculopathy, myelopathy, Ramsay-Hunt syndrome, and polyneuritis cranialis. Cranial nerves V, VI, VII, VIII, IX, X, XI, and/or XII may be affected. The neurological disorders caused by VZV usually present with rash, but may rarely present without rash. CASE REPORT: We herein present a case of polyneuritis cranialis without rash caused by VZV affecting cranial nerves VII, VIII, IX, and X. After excluding other causes of the condition, we diagnosed VZV infection based on VZV DNA in the CSF and an elevated anti-VZV IgG level in serum. The patient responded well to antiviral therapy. CONCLUSION: VZV infection should be kept in mind during the differential diagnosis of polyneuritis cranialis; it is important to note that VZV re-activation may occur without rash.

Hesperidin, a Citrus Flavonoid, Has the Ameliorative Effects Against Experimental Autoimmune Encephalomyelitis (EAE) in a C57BL/J6 Mouse Model.

The aim of this study was determined the effects of Hesperidin (HP) on neuronal damage in brain tissue caused by Experimental allergic encephalomyelitis (EAE), an established model of multiple sclerosis in C57BL/J6 mice. To explore 40 mice were equally divided into four groups: (1) Control, (2) EAE, (3) HP, and (4) HP + EAE. 14 days after induction of EAE with MOG35-55 and pertussis toxin, the mice treated with HP at the doses of 50 mg/kg/day for 7 days subcutaneously. To our results HP treatment prevents the oxidative stress caused by EAE via a decrease in lipid peroxidations and increase in elements of the antioxidant defense systems in brain tissue. Also, EAE elevate the IL-17, express the pro-inflammatory cytokines, and caspase-3-like immunreactivity, show apoptosis, staining in EAE mice brain and increased the incidence of histopathological damage. However, immonohistochemical and histological changes were reversed with HP. Moreover, elevated TNF-α and IL-1ß levels, a result of EAE, were decreased in serum and neurological deficits as clinical signs were reversed with HP treatment in EAE mice, given HP. In conclusion, HP treatment effectively prevents oxidative, immunological and histological damage in the brain caused by EAE. It was thought that the beneficial effects of HP are likely a result of its strong antioxidant and anti-inflammatory properties.

What are the Predictors of Death in Patients With Cranio-Cervical Artery Dissection?

INTRODUCTION: Few studies have reported the predictive factors related to mortality in patients with cranio-cervical artery dissections (CCAD). Our aim was to investigate the predictors related to in-hospital mortality in patients with CCAD and its subgroups. METHODS: Sixty-seven patients diagnosed with carotid artery dissection (CAD) or vertebral artery dissection (VAD), admitted to our clinic between 2000 and 2013, were retrospectively reviewed. Age, gender, modified Rankin Scale scores (pre-stroke and at admission), clinical presentation type, location of the dissection, risk factors, and treatments were analyzed as mortality-related prognostic factors. Of the 67 patients, 12 (17.9%) died, five (7.46%) with CAD and seven (10.44%) with VAD. We compared the prognostic characteristics of the surviving versus deceased patients with CCAD and in the subgroups with CAD and VAD. RESULTS: Age above 45 years, severe disability at admission, presentation with stroke, and intracranial VAD occurred more frequently in deceased patients and were independent variables related to mortality in patients with CCAD and its subgroup with VAD. Severe disability at admission alone was related to mortality in patients with CAD. Hypertension and hypercholesterolemia were independent variables related to mortality in patients with CCAD. CONCLUSION: Severe disability at admission was a mortality predictor in both CAD and VAD. Although the initial severity of stroke is reportedly related to poor outcomes in patients with CCAD, it has not previously been directly identified as a predictor of mortality in patients with CAD or VAD.

Hesperidin protects brain and sciatic nerve tissues against cisplatin-induced oxidative, histological and electromyographical side effects in rats.

In the present study, the beneficial effect of hesperidin (HP), a citrus flavonoid, on cisplatin (CP)-induced neurotoxicity was investigated. A total of 28 rats were equally divided into four groups; the first group was kept as control. In the second and third groups, CP and HP were given at the doses of 7 and 50 mg/kg/day, respectively. In the fourth group, CP and HP were given together at the same doses. The results indicated that although CP caused significant induction of lipid peroxidations and reduction in the antioxidant defense system potency in the brain and sciatic nerve, HP prevented these effects of CP. Besides, CP led to histopathological damage, mainly apoptosis, as well as electromyographical (EMG) changes in sciatic nerve. On the other hand, HP treatment reversed histopathological and EMG effects of CP. In conclusion, CP had severe dose-limiting neurotoxic effects and these effects of CP can be prevented by HP treatment. Thus, it appears that coadministration of HP with CP may be a useful approach to attenuate the negative effects of CP on the nervous system.

Comparison of nerve, vessel, and cartilage grafts in promoting peripheral nerve regeneration.

Peripheral nerve injury primarily occurs due to trauma as well as factors such as tumors, inflammatory diseases, congenital deformities, infections, and surgical interventions. The surgical procedure to be performed as treatment depends on the etiology, type of injury, and the anatomic region. The goal of treatment is to minimize loss of function due to motor and sensory nerve loss at the distal part of the injury. Regardless of the cause of the injury, the abnormal nerve regeneration due to incomplete nerve regeneration, optimal treatment of peripheral nerve injuries should provide adequate coaptation of proximal and distal sides without tension, preserving the neurotrophic factors within the repair line. The gold standard for the treatment of nerve defects is the autograft; however, due to denervation of the donor site, scarring, and neuroma formation, many studies have aimed to develop simpler methods, better functional results, and less morbidity. In this study, a defect 1 cm in length was created on the sciatic nerve of rats. The rats were treated with the following procedures: group 1, autograft; group 2, allogeneic aorta graft; group 3, diced cartilage graft in allogeneic aorta graft; and group 4, tubularized cartilage graft in allogeneic aorta graft. Group 5 was the control group. The effects of cartilage tissue in nerve regeneration were evaluated by functional and histomorphological methods.Group 1, for which the repair was performed with an autograft, was evaluated to be the most similar to the control group. There was not a statistically significant difference in myelination and Schwann cell rates between group 2, in which an allogeneic aorta graft was used, and group 3, in which diced cartilage in an allogeneic aorta graft was used. In group 4, myelination and Schwann cell formation were observed; however, they were scattered and irregular, likely due to increased fibrosis.In all of the groups, nerve regeneration at various rates was observed both functionally and histomorphologically. This study demonstrates that cartilage tissue has promoting effects in nerve regeneration.

Neuromuscular transmission in hypoxemic patients with chronic obstructive pulmonary disease.

Many studies have focused on the systemic effects of chronic obstructive pulmonary disease (COPD), but none has examined neuromuscular junction transmission (NMT). We evaluated NMT dysfunction using single-fiber electromyography (SFEMG) in patients with COPD. Twenty patients with COPD and 20 age-matched healthy controls were included in the study. All patients and controls underwent SFEMG. Abnormal NMT was found in seven of 20 patients (35%), but in none of the control subjects. The COPD patients were subgrouped according to the presence of hypoxemia. The patients with normoxemia were classified as Group 1, and the patients with hypoxemia were classified as Group 2. Abnormal NMT was found in six patients in Group 2 and in one in Group 1. While there was significant difference in terms of abnormal NMT between Group 2 and the controls, there was none between Group 1 and the controls. Our results show that NMT abnormalities can be present in hypoxemic patients with COPD.

The prognostic value of an increased mean platelet volume and platelet distribution width in the early phase of cerebral venous sinus thrombosis.

In this study, we aimed to investigate the value of mean platelet volume (MPV), platelet distribution width (PDW) and platelet count in cerebral venous sinus thrombosis (CVST) patients and in control subjects. Fifty-three patients with evidence of CVST and thirty-five controls with similar baseline characteristics were included in the study. CVST patients were further divided into two subgroups based on the presence or absence of parenchymal lesions in cranial MRI. Our analyses revealed a significant difference in MPV and PDW values between CVST patients with lesions and controls (P < 0.05). MPV and PDW values were significantly increased in CVST patients with brain parenchmal lesions, suggesting that MPV and PDW values can be used to predict the severity of CVST.

Lower extremity isokinetic muscle strength in patients with Parkinson's disease.

We evaluated lower extremity isokinetic muscle strength to determine affected muscle groups and their dependence on movement velocity, and to establish the relationship between muscle strength and clinical severity, as well as muscle strength and falls, in Parkinson's disease (PD). Twenty-five patients diagnosed with PD and 24 healthy volunteers were enrolled in this study. Lower extremity muscle strength was measured using an isokinetic dynamometer. Each participant's clinical status was examined in accordance with the Unified Parkinson's Disease Rating Scale; fall history was also recorded. We observed a significant decrease in isokinetic muscle strength in the patient group, especially in both hip and knee flexors and extensors. Decreased muscle strength was independent of velocity, and correlated with clinical severity and falls. Movement velocity-independent lower extremity isokinetic muscle weakness has been observed in patients with PD, especially in the knee and hip joints. The evaluation of isokinetic muscle strength may be a useful tool for the assessment of clinical severity and falls in PD.

Single-voxel magnetic resonance spectroscopy of brain tissue adjacent to arachnoid cysts of epileptic patients.

Intracranial arachnoid cysts (ACs) are usually asymptomatic, benign developmental anomalies. The most frequent clinical manifestations are cranial expansion, hydrocephaly, headache, epileptic seizures, psychomotor retardation, and aphasia. It is unknown whether there is a correlation between intracranial AC and epileptic seizures without obvious intracranial pressure signs. In vivo magnetic resonance spectroscopy is a technique used for the noninvasive investigation of the various metabolites of cerebral biochemical reactions. Magnetic resonance spectroscopy is also being used increasingly commonly in epileptogenic situations as a noninvasive technique. The purpose of this study was to evaluate the proton magnetic resonance spectroscopic pattern of the contents of tissue adjacent to AC and to determine whether there are any characteristic spectral patterns that may be helpful in evaluating whether these lesions are epileptogenic foci. In conclusion, although the number of cases was limited, this finding may be seen as indicating that there is no association between AC and epilepsy.

[The effect of human placental suspension on rat sciatic nerve healing]. / Siçan siyatik sinir iyilesmesinde insan plasenta süspansiyonunun etkisi.

OBJECTIVES: We investigated the effect of human placental suspension (HPS) on rat sciatic nerve regeneration. METHODS: Eight adult female Sprague-Dawley rats weighing between 250 and 300 g were randomly divided into control and study groups equal in number. Both sciatic nerves were explored under anesthesia, transsected and then immediately repaired. At the end of the operation, and on the second and fifth days, HPS and saline were administered to the operation zone in the test and control groups, respectively. For functional examination, electromyographic activity was measured in posterior extremities of all rats preoperatively and at the end of eight weeks. The rats were then sacrificed to obtain transections from the repaired area and its distal region for histologic examination and the number of myelin-sheathed axons was estimated in both regions. RESULTS: Electromyographic study showed delayed latency and decreased amplitude following operation in both groups, being less severe in the study group without reaching a significant difference from the control group (p>0.05). The most notable histopathologic finding was increased endoneural collagen in the control group and regenerative axonal growth in the HPS group. The number of axons was greater in the distal region in both groups. In both regions, the number of myelin-sheathed axons was greater in the HPS group, but this difference was significant only for the number of axons in the repair zone (p=0.001). CONCLUSION: Our data suggest that HPS may exert a favorable effect on peripheral nerve regeneration.