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Opinion Statement: Neurologic involvement in Behçet's disease (BD) is seen in about 5% to 10% of all BD patients. Clinical and imaging data suggest that neurologic involvement in BD presents in two major forms. The first, central nervous system (CNS) parenchymal involvement with a predilection to brainstem-diencephalic regions, is seen in the majority of patients with neuro-BD (NBD). The second form is cerebral venous sinus thrombosis (CVST), which is seen in up to 20% of cases. BD is very rare in children, but when it does occur, the patterns are reversed: most children with NBD present with CVST. Other syndromes such as spinal cord involvement, arterial CNS involvement, optic neuritis, aseptic meningitis, and peripheral neuropathies may be seen, but are rare. Venous sinus thrombosis in BD has a significantly better neurologic prognosis than parenchymal CNS involvement. There is no Class I evidence regarding treatment of parenchymal CNS involvement or CVST in BD. Current treatment applications are based largely on expert opinion; none are evidence-based. Acute parenchymal CNS involvement should be treated with high-dose intravenous methylprednisolone (IVMP), 1 g per day, for 5 to 10 days, followed by either a prolonged oral taper or intermittent IVMP pulses with a low oral dose between the pulses, over 6 months. After treatment of the acute attack, long-term maintenance with immunosuppressive agents should be considered in patients with parenchymal CNS involvement, as this form may follow a relapsing or secondary progressive course and may result in significant physical and cognitive deficits leading to severe neurologic disability. A number of randomized controlled studies have tested treatments for systemic manifestations of BD. Colchicine was found to be effective for mucocutaneous symptoms, thalidomide was found to be effective in erythema nodosum-like skin lesions, azathioprine and cyclosporine were shown to be effective in BD uveitis, and cyclophosphamide was shown to be effective for major vascular involvement. More recently, interferon alfa and anti-TNF agents were also shown to be effective in BD uveitis. Although randomized controlled studies have not been performed in NBD, the most widely used long-term therapeutic agent is azathioprine. Recent observations suggest that the addition and long-term use of azathioprine in NBD could be associated with a more favorable course. A growing number of case reports in recent years suggest that anti-TNF agents may be an effective alternative in NBD, but current experience with these agents is limited. CVST in BD is also treated with steroids. The addition to glucocorticoids of anticoagulation, including short-term fractionated heparin, is controversial, as these patients have a higher probability of harboring pulmonary or other aneurysms, which may be associated with an increased risk of bleeding. Long-term oral anticoagulation is unnecessary. Interestingly, the prognosis of CVST due to BD seems to be much more favorable than the prognosis of CVST due to other causes, with much less tendency for venous infarcts and seizures. However, as recurrences may occur, long-term treatment with azathioprine is recommended.

Background: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance., Methods: The UmanDiagnostics NF-light (R)enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses., Results: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R=0.60, p<0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R=0.98, p<0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics., Conclusion: This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online., (Copyright 2009 Elsevier B.V. All rights reserved.)

Purpose: To assess the outcome of urologic evaluation in patients with voiding dysfunction due to multiple sclerosis (MS) and to determine the relationship between urological and neurological parameters of these patients., Materials and Methods: We retrospectively reviewed the medical records of 249 consecutive patients (162 female and 87 male) with MS who were referred to our clinic between 1991 and 2006, with a median time of 4 years (range 3 months to 26 years) of MS onset. Data was analyzed with respect to patient demographics and findings of initial evaluation. Lower urinary tract symptoms were evaluated by Boyarsky symptom index., Results: All patients except 13 had lower urinary tract symptoms and 70% manifested mixed symptoms. Total, storage and voiding symptom scores correlated with expanded disability status scale scores (p < 0.05). Twelve patients (5%) had abnormal upper urinary tract. Ultrasound findings of lower urinary tract were abnormal in 12 patients (5%). No demographic parameters were associated with abnormal findings of upper urinary tract on univariate analysis. Urodynamic evaluation of 75 patients (30.1%) revealed detrusor overactivity with or without detrusor-sphincter dyssynergia in 56 (75%). No correlation was found between urodynamic diagnosis and upper tract deterioration and urinary symptom scores (p > 0.05)., Conclusions: The prevalence of mixed symptoms in patients with MS is higher than storage or voiding symptoms alone. Although detrusor overactivity and detrusor-sphincter dyssynergia were the most common urodynamic diagnoses, upper urinary tract deterioration was rare in our series.

Behçet's Syndrome (BS) is a multi-system, vascular-inflammatory disease of unknown origin, involving the nervous system in a subgroup of patients. The growing clinical and imaging evidence suggests that primary neurological involvement in BS may be subclassified into two major forms: the first one, which is seen in the majority of patients, may be characterized as a vascular-inflammatory central nervous system (CNS) disease, with focal or multifocal parenchymal involvement mostly presenting with a subacute brainstem syndrome and hemiparesis; the other, which has few symptoms and a better neurological prognosis, may be caused by isolated cerebral venous sinus thrombosis and intracranial hypertension. These two types rarely occur in the same individual, and their pathogenesis is likely to be different. Isolated behavioral syndromes and peripheral nervous system involvement are rare, whereas a nonstructural vascular type headache is relatively common and independent from neurological involvement. Neurologic complications secondary to systemic involvement of BS such as cerebral emboli from cardiac complications of BS and increased intracranial pressure due to superior vena cava syndrome, as well as neurologic complications related to BS treatments such as CNS neurotoxicity with cyclosporine and peripheral neuropathy with the use of thalidomide or colchisin are considered as secondary neurological complications of this syndrome. As the neurological involvement in this syndrome is so heterogeneous, it is difficult to predict its course and prognosis, and response to treatment. Currently, treatment options are limited to attack and symptomatic therapies with no evidence for the efficacy of any long term preventive treatment.

The objectives of this study were to determine the age and sex dependent linear trend of recurrent headache prevalence in schoolchildren in Mersin. A stratified sample composed of 5562 children; detailed characteristics were previously published. In this study the prevalence distribution of headache by age and sex showed a peak in the female population at the age of 11 (27.2%) with a plateau in the following years. The great stratified random sample results suggested that, in addition to socio-demographic features, detailed linear trend analysis showed headache features of children with headache have some specific characteristics dependent on age, gender and headache type. This study results can constitute a basis for the future epidemiological based studies.

This study was planned to investigate the economic impact of headache on Turkish headache sufferers attending a tertiary care outpatient headache clinic.A total of 937 headache patients were included in this study and questioned using a questionnaire for the profile of patients and headache, quality of life of patients and economic impact of headache. The median total direct cost was found to be 88.0 USD and the median total cost was 160.7 USD. The drug treatment cost was the highest item followed by the specialist outpatient care cost. The average lost and inefficient work/school days was 1.5 (0-45) and 8.4 (0-100) days for one year. It was shown that loss of productivity was higher for migraine without aura group when compared with the episodic and chronic tension-type headache groups. The results of this nationwide university hospital based study methshowed that headache, especially migraine, has considerable economic impact on patients.

An increasing number of patients referred for neuroimaging studies unrelated to multiple sclerosis (MS) are found to have incidental lesions suggestive of MS in their nervous systems but many such patients do not develop clinical symptoms and signs and remain as "subclinical MS" (SCMS). MRI and cerebrospinal fluid (CSF) studies in monozygotic twins and siblings of MS patients, as well as necropsy studies in asymptomatic persons also reveal findings consistent with SCMS. Clinically isolated syndromes (CIS), acute disseminated encephalomyelitis (ADEM), benign MS, relapsing-remitting MS, primary and secondary progressive MS, optico-spinal MS, Balo's and Marburg's diseases, are considered different forms of MS by many because of their heterogeneous clinical, imaging and pathological features. Studies of disease susceptibility, type, course and severity have given different results in different populations, consistent with "genetic heterogeneity". The various forms of the disease may change from one to another, and their clinical and imaging features became similar after a number of years. The current data support the concept that MS, whether it is a single disease or a group of disorders, is an immune-mediated disease of the CNS, with both inflammatory and degenerative features with available therapies being only partially and temporarily effective for the inflammatory phase of the disease. Making the diagnosis of MS may not be an absolute indication for early treatment with disease modifying agents. The use of new technology such as microarray and other techniques in diagnosing and understanding the MS spectrum may make it possible to recognize the different molecular subtypes of these diseases and develop better therapies.

Objective: To study the frequencies and characteristics of different headache types seen in patients with Behçet's syndrome (BS) in a large cohort of patients., Background: Patients with BS may present with different neurological problems, related either directly or indirectly to the disease, with headache being the most common neurological symptom seen in this syndrome, as well as independent from neurologic involvement., Method: This study was carried out at the multidisciplinary Behçet outpatient clinic of the Behçet's Syndrome Research Center. Every fifth admitted patient who had fulfilled the International Study Group for Behçet's Disease classification criteria was recruited for this study. Each patient was interviewed by one of the examining neurologists through a semistructured questionnaire. In case of the presence of more than one headache type, the best defined one was diagnosed and evaluated. All patients received a complete neurological and physical examination. A chi(2) test was used to evaluate the differences between frequencies. One sample t-test was used to compare means. The prevalence rates of primary headaches were compared with results of the Turkish Headache Epidemiology study by using goodness-of-fit test., Results: Two hundred and twenty-eight patients were studied. Headache was reported in 66.2% (151/228) of the study cohort. Primary headaches were seen in 38.6% of the patient population, which corresponds to 58% of BS patients with any type of headache. Tension-type headache (TTHA) and migraine were seen in 23.6% and 14.9% of the whole study cohort, respectively. In 5.2% of the study cohort, the headache was associated with neurological involvement and in 3.9% to uveal inflammation. A predominantly frontal, bilateral paroxysmal throbbing pain of moderate severity was reported in 18.4% of the study cohort who did not fulfill the criteria of the International Headache Society (IHS) for any of the primary headaches. It was commonly associated with exacerbations of the mucocutaneous symptoms of the syndrome. The neurological examination was normal in all of these patients. This type of headache was categorized as the nonstructural headache of Behçet., Conclusion: Headache is the most common neurological symptom seen in BS, both in patients with and without neurological involvement. The results of our study reveal that headache is seen in a majority of patients with neurological involvement due to BS and in a minority with uveal inflammation. The prevalence of migraine and TTHA are close to the population in general, but a nonstructural migrainous headache, which is commonly associated with exacerbations with some of the systemic symptoms of the syndrome, is noteworthy in patients with BS. This form of headache is not specific for this disorder, but may be explained by a vascular headache triggered by the immunomediated disease activity in susceptible individuals.

Objectives: The aim of this study is to assess the comprehensibility, internal consistency, patient-physician reliability, test-retest reliability, and validity of Turkish version of Migraine Disability Assessment (MIDAS) questionnaire in patients with headache., Background: MIDAS questionnaire has been developed by Stewart et al and shown to be reliable and valid to determine the degree of disability caused by migraine., Design and Methods: This study was designed as a national multicenter study to demonstrate the reliability and validity of Turkish version of MIDAS questionnaire. Patients applying to 17 Neurology Clinics in Turkey were evaluated at the baseline (visit 1), week 4 (visit 2), and week 12 (visit 3) visits in terms of disease severity and comprehensibility, internal consistency, test-retest reliability, and validity of MIDAS. Since the severity of the disease has been found to change significantly at visit 2 compared to visit 1, test-retest reliability was assessed using the MIDAS scores of a subgroup of patients whose disease severity remained unchanged (up to +/-3 days difference in the number of days with headache between visits 1 and 2)., Results: A total of 306 patients (86.2% female, mean age: 35.0 +/- 9.8 years) were enrolled into the study. A total of 65.7%, 77.5%, 82.0% of patients reported that "they had fully understood the MIDAS questionnaire" in visits 1, 2, and 3, respectively. A highly positive correlation was found between physician and patient and the applied total MIDAS scores in all three visits (Spearman correlation coefficients were R= 0.87, 0.83, and 0.90, respectively, P <.001). Internal consistency of MIDAS was assessed using Cronbach's alpha and was found at acceptable (>0.7) or excellent (>0.8) levels in both patient and physician applied MIDAS scores, respectively. Total MIDAS score showed good test-retest reliability (R= 0.68). Both the number of days with headache and the total MIDAS scores were positively correlated at all visits with correlation coefficients between 0.47 and 0.63. There was also a moderate degree of correlation (R= 0.54) between the total MIDAS score at week 12 and the number of days with headache at visit 2 + visit 3, which quantify headache-related disability over a 3-month period similar to MIDAS questionnaire., Conclusion: These findings demonstrated that the Turkish translation is equivalent to the English version of MIDAS in terms of internal consistency, test-retest reliability, and validity. Physicians can reliably use the Turkish translation of the MIDAS questionnaire in defining the severity of illness and its treatment strategy when applied as a self-administered report by migraine patients themselves.

Purpose of Review: Behçet's syndrome (BS) is a multi-system, vascular-inflammatory disease of unknown origin, involving the nervous system in a subgroup of patients. The syndrome is rare, but as patients with BS are young and frequently present with an acute or subacute brainstem syndrome or hemiparesis, as well as with other various neurological manifestations, the syndrome is often included in the differential diagnosis of multiple sclerosis, stroke of the young adult, and another wide range of neurological disorders. The present review summarizes the neurological involvement in BS, and emphasizes recent clinical concepts and ethiopathogenetic findings., Recent Findings: Over the last years the growing clinical and imaging evidence had suggested that neurological involvement in BS may be subclassified into two major forms: one, which is seen in the majority of patients, may be characterized as a vascular-inflammatory CNS disease, with focal or multifocal parenchymal involvement; the other, which has few symptoms and a better neurological prognosis, may be caused by isolated cerebral venous sinus thrombosis and intracranial hypertension. These two types rarely occur in the same individual, and their pathogenesis is likely to be different. A nonstructural vascular type headache is relatively common, whereas isolated behavioral syndromes and peripheral nervous system involvement are rare., Summary: The involvement of the nervous system in BS is heterogeneous as clinical and imaging data reveal. Currently it is unknown which factors determine or have a role in the development of neurological involvement, but some progress has been achieved in understanding the neurological spectrum of the syndrome, which may lead to a better management of these patients.