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OBJECTIVE: Neurotransmitter systems participate in the regulation of food intake, and their activities are expected to influence eating behavior. DESIGN AND METHODS: We investigated possible associations between body mass index (BMI) and central noradrenaline, serotonin, and dopamine activities, as reflected by the cerebrospinal fluid levels of their main metabolites methoxyhydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA), respectively. We studied 192 subjects (111 males, 81 females) admitted to neurologic clinic for diagnostic investigations that included CSF analysis, and were found not to suffer from any major neurological disease. Subjects were categorized in three groups, namely in lower, in the two middle, and in upper BMI quartiles, the limits calculated separately for males and females. RESULTS: No differences were found in MHPG levels between groups, while subjects in the upper BMI quartile showed significantly elevated levels of 5-HIAA and HVA compared to the levels of subjects in lower and middle quartiles. CONCLUSIONS: The results provide evidence that in overweight subjects there are enhanced demands in serotoninergic and dopaminergic signaling for their reward system that may lead to increased motivation for food consumption. The implication of reward centers in eating behavior supports the hypothesis of common mechanisms in obesity and drug addiction.

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A 45-year-old female suffering from severe thoracic pain was admitted to the emergency department of our hospital. Thorough clinical examination revealed paresis of the left lower limb and sensory deficit at the level of the Th4 vertebra. MRI of the thoracic spine demonstrated a lesion at the level of Th1-Th7. Despite initial improvement following i.v. corticosteroid administration, the patient's clinical status deteriorated, with recurrence of myelitis and extension of the lesion to Th12. She developed paraparesis, hyperreflexia and spasticity of both legs, symmetrical sensory deficit below Th4, and sphincter dysfunction. Differential diagnosis included infectious, metabolic, neoplastic/paraneoplastic, and ischemic causes as well as multiple sclerosis. NMO IgG was found positive and led to the diagnosis of longitudinal extensive transverse myelitis (LETM) in the NMO spectrum disorders. Administration of immunosuppressive therapy resulted in gradual improvement of the patient's clinical status and stabilization for five years. In the setting of LETM, patients with antiaquaporin 4 IgGs can present features of coexisting systemic involvement. A thorough differential diagnosis is required to guide appropriate therapy.

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BACKGROUND/AIMS: The onset of multiple sclerosis (MS) in Greece has not been systematically studied. We sought to provide data on the onset of MS in Greece with detailed information regarding initial symptoms, and to confirm the prognostic significance of demographic and clinical factors at onset. METHODS: We studied 1,034 consecutive patients with MS and independently assessed 265 patients 'seen at onset'. We used the MS severity score and survival analysis (time to reach an Expanded Disability Status Scale score of 4.0) to evaluate the prognostic significance of factors at onset. RESULTS: Female-to-male ratio was 1.9:1 and mean age at onset was 30.7 +/- 9.9 years. MS was primary progressive in 9.6%. Initial symptoms were optic neuritis in 20.1%, brainstem dysfunction in 14.7%, dysfunction of long tracts in 49.3%, cerebral dysfunction in 1% and a combination of symptoms in 14.9%. In 'seen at onset' patients, detailed data on initial symptoms are presented. Female gender, earlier age at onset, 'bout onset' and onset with optic neuritis were associated with less severe disease and longer time to disability. CONCLUSION: The onset of MS in Greece is similar to Western populations. Initial symptoms are within the expected spectrum. Prognostic significance of factors at onset is as previously identified.

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There is considerable evidence that prolactin (PRL) exerts immunomodulatory actions, thus being involved in the processes of autoimmune diseases. Animal studies suggest that elevated serum PRL levels may be related to neuroprotection or participate in remyelination after brain injury. To address this question, we estimated PRL levels in both serum and cerebrospinal fluid (CSF) in drug-free male and female patients with clinically-isolated syndrome (CIS) suggestive of MS (i.e. after the first episode) as well as in patients with relapsing-remitting (RR) MS after two or more relapses, and related them to clinical, paraclinical and laboratory data. Seventy two patients with RR MS and 80 patients with CIS in the age range 17-61 years were studied. PRL levels of patients were compared with 74 control subjects, separately for males and females. Significantly higher PRL levels in serum and CSF were found in female RRMS patients but not in males. Patients with CIS had normal PRL levels. No associations were found with disease activity, duration of illness, presence of active lesions or the presence of oligoclonal bands in CSF. The elevated PRL levels observed in female but not in male RRMS patients, or in patients with CIS, could be suggestive of a sexually dimorphic response to central nervous system injury as a result of an increased proneness of females to synthesise and release PRL, which is possibly linked to the relatively more favourable prognosis of MS in women.

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BACKGROUND: Elevated ApoA1 levels have been associated with decreased dementia risk. The A-allele of the APOA1 -75G/A promoter polymorphism has been associated with elevated ApoA1 levels. OBJECTIVE: We sought to investigate the effect of the APOA1 -75G/A promoter polymorphism on cognitive performance in patients with multiple sclerosis (MS). METHODS: A total of 138 patients with MS and 43 controls were studied and underwent neuropsychological assessment with Rao's Brief Repeatable Battery and the Stroop test. All patients were genotyped for APOA1. RESULTS: APOA1 A-allele carriers displayed superior overall cognitive performance compared with non-carriers (P 0.008) and had a three-fold decrease in the relative risk of overall cognitive impairment (OR 0.29, 95% CI 0.11-0.74). Regarding performance on individual cognitive domains, although APOA1 A-allele carriers performed better than non-carriers on all tests, this was significant only for semantic verbal fluency and the Stroop interference task (P 0.036 and 0.018, respectively). CONCLUSIONS: We found an association of the APOA1 -75G/A promoter polymorphism with cognitive performance in MS. This effect was most prominent on semantic verbal fluency and the Stroop interference task.

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OBJECTIVE: Self-reported stressful life events and infections have been associated with relapses in multiple sclerosis. Also, anxiety has been reported to influence other diseases of unpredictable course. To study relation of self-reported stressful life events, levels of anxiety, and episodes of infection, with relapses of the disease in women with multiple sclerosis. METHODS: This is a one-year prospective study. Thirty seven women with multiple sclerosis were regularly seen every four weeks, for one year. They were keeping diaries of events they considered stressful. These events were ranked according to the Holmes and Rahe Social Readjustment Rating Scale. Their anxiety levels were assessed with the Hamilton rating scale for anxiety. Relapses and episodes of infection were verified at additional visits. Results were studied using a survival analysis model adapted for several recurrent events. RESULTS: A total of 291 stressful events, 37 episodes of infection, and 48 relapses, were registered. High level of anxiety were stongly related to the number and the severity of reported stressful events during the preceding period and with the advent of a relapse in the following period (Hamilton score greater than 18 is associated with 4.2 times the rate of relapsing and three or more reported stressful events with 5.7 times the rate of relapsing). CONCLUSIONS: Anxiety and self-reported stressful events may in fact be two measures of the same underlying emotional factor, which plays an important role on the course of the disease, in addition to episodes of infection.

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BACKGROUND: Spastic paretic hemifacial contracture (SPHC) is an uncommon condition, originally described as a sign of brainstem neoplasia, characterized by sustained unilateral contraction of the facial muscles associated with mild ipsilateral facial paresis. SPHC has only rarely been reported in the context of multiple sclerosis (MS). To further study and assess the frequency of SPHC in patients with MS. METHODS: We screened clinically 500 consecutive patients with MS for the presence of SPHC and further studied electrophysiologically any cases identified. RESULTS: We identified two patients who developed the condition during the course of an MS relapse. The estimated frequency of the condition was 0.4%. Both patients had relapsing-remitting MS. SPHC was characterized on Electromyography (EMG) by continuous resting activity of irregularly firing motor unit potentials, associated with impaired recruitment of motor units on voluntary contraction. Myokymic discharges were not present. Blink reflex studies were partly consistent with midpontine lesions in the vicinity of the facial nucleus ipsilateral to SPHC. MRI showed lesions in the ipsilateral dorsolateral midpontine tegmentum. CONCLUSIONS: SPHC constitutes a rare but distinct clinical and EMG entity in patients with MS.

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Although both multiple sclerosis (MS) and systemic lupus erythematosus (SLE) are relatively common autoimmune disorders, especially in young women and often coexist in families, they are only rarely reported to coexist in a single patient. We here present a case of a young woman with a history of MS from many years who diagnosed as suffering as well from SLE.

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Stiff person syndrome (SPS) is a rare neurological disorder characterised by muscular rigidity and superimposed spasms of the trunk and limbs that may be precipitated by voluntary movements and unexpected tactile, auditory or emotional stimulation. The high prevalence of autoantibodies against glutamic acid decarboxylase (antiGAD) in both serum and cerebrospinal fluid, as well as the frequent association of SPS with other autoimmune disorders, suggest an autoimmune pathogenesis. SPS is frequently misdiagnosed as axial dystonia or psychogenic movement disorder. We report a patient with SPS in order to emphasise the reasons for this common misdiagnosis.

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OBJECTIVE: To investigate the effect of APOE epsilon4 on different cognitive domains in a population of Greek patients with multiple sclerosis (MS). METHODS: A total of 125 patients with MS and 43 controls were included in this study and underwent neuropsychological assessment with Rao's Brief Repeatable Battery. All patients with MS were genotyped for APOE. The effect of APOE epsilon4 on different cognitive domains was investigated. RESULTS: Fifty-one percent of patients with MS were cognitively impaired. E4 carriers had a sixfold increase in the relative risk of impairment in verbal learning vs noncarriers (OR 6.28, 95% CI 1.74 to 22.69). This effect was domain-specific and was not observed in other cognitive domains assessed by the battery. CONCLUSION: We found an association of APOE epsilon4 with impaired verbal learning in patients with multiple sclerosis.

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The aim of the present study was the quantitation of total tau protein (tau(T)), tau phosphorylated at threonine 181 (tau(P-181)) and beta-amyloid(1-42) (Abeta42) in the cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH), Alzheimer's disease (AD) and controls. Double sandwich ELISAs (Innogenetics) were used for the measurements. Total tau was significantly increased in iNPH and highly increased in AD as compared with the control group, whilst Abeta42 was decreased in both diseases. CSF tau(P-181) levels were significantly increased only in AD, but not in iNPH as compared with the controls. A cut-off level for tau(T) at 300 pg/ml, successfully discriminated AD from normal aging with a 95.8% specificity and 91% sensitivity; whilst the tau(P-181)/tau(T) ratio (cut-off value 0.169) was more specific (100%) but less sensitive (92.5%). For the discrimination of iNPH from AD tau(T) achieved low specificity (77.8%) but high sensitivity (92.5%), whilst tau(P-181) (cut-off value 47.4) was both sensitive and specific (88.7% and 86.7% respectively) for the discrimination of these disorders. The present study, despite being clinical, supports the notion that CSF tau(P-181) alone or in combination with tau(T) may be a useful marker in the discrimination of iNPH from AD.

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OBJECTIVES: We evaluated cross-sectionally the associations of depression and anxiety with age, sex, duration of illness, educational level, degree of disability and treatment with interferon-beta in outpatients with relapsing-remitting multiple sclerosis (RRMS) during a clinically stable phase of their illness. MATERIALS AND METHODS: The depression status scored on the Beck Depression Inventory (BDI), the symptoms of anxiety assessed using the State Trait Anxiety Inventory (STAI) and the level of disability measured by the Expanded Disability Status Scale (EDSS) were quantified in 86 consecutive RRMS patients. RESULTS: Linear regression analyses indicated that EDSS was independently (P < 0.001) associated with BDI and STAI and accounted for 15.7% and 18.5% of the variance in BDI and STAI respectively. The former association retained its statistical significance in multiple regression models adjusting for demographic and clinical characteristics. CONCLUSIONS: Disability status is an independent but moderate determinant of depression and anxiety in MS patients.

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Our purpose was to evaluate the role of magnetization transfer and image subtraction in detecting more enhancing lesions in brain MR imaging of patients with multiple sclerosis (MS). Thirty-one MS patients underwent MR imaging of the brain with T1-weighted spin echo sequences without and with magnetization transfer (MT) using a 1.5 T imager. Both sequences were acquired before and after intravenous injection of a paramagnetic contrast agent. Subtraction images in T1-weighted sequences were obtained by subtracting the pre-contrast images from the post-contrast ones. A significant difference was found between the numbers of enhanced areas in post-gadolinium T1-weighted images without and with MT (p=0.020). The post-gadolinium T1-weighted images with MT allowed the detection of an increased (13) number of enhancing lesions compared with post-gadolinium T1-weighted images without MT. A significant difference was also found between the numbers of enhanced areas in post-gadolinium T1-weighted images without MT and subtraction images without MT (p=0.020). The subtraction images without MT allowed the detection of an increased (10) number of enhancing lesions compared with post-gadolinium T1-weighted images without MT. Magnetization transfer contrast and subtraction techniques appear to be the simplest and least time-consuming applications to improve the conspicuity and detection of contrast-enhancing lesions in patients with MS.

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BACKGROUND: Recently, the P600 component of event related potentials, a waveform that is conceived to be generated and/or modulated by basal ganglia and cingulate area has been considered an index of the completion of any synchronised operation after target detection, having much in common with working memory operation. Moreover, dysfunction of these brain structures as well as working memory deficits have been implicated in the pathophysiology of multiple sclerosis. The aim of this study was to investigate the patterns of P600 elicited during a working memory test in multiple sclerosis patients compared with healthy controls. METHODS: Twenty two definite, chronic progressive multiple sclerosis patients, with recent exacerbation of their illness, and 20 normal subjects matched for age, sex, and educational level, were studied with a computerised version of the digit span test of Wechsler batteries. Auditory P600 were measured during the anticipatory period of this test. RESULTS: The patient group, as compared with healthy controls, showed significantly reduced latencies of P600 at left frontal areas and reduced P600 amplitudes at left temporoparietal region. Moreover, memory performance of patients was significantly more impaired when compared with healthy controls. CONCLUSIONS: These findings may indicate that multiple sclerosis is associated with abnormal features of the completion of synchronised operation after target detection, as they are reflected by P600 amplitudes and latencies. Dysfunction of this mechanism may contribute to the identification of basic cognitive processes that could account for the cognitive deficits in multiple sclerosis.

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Event-related potentials (ERPs) were elicited in 30, non-consecutive, non-demented individuals, complaining of short-term memory disturbances. Fifteen of them had a moderate diffuse cerebral atrophy on their brain CT and the other 15 had a negative brain CT. ERPs were also elicited in 15 age-matched controls with no reported memory disturbances and negative brain CTs. The statistical analysis showed that the group of individuals with cerebral atrophy had a significantly prolonged P300 (P3) latency and a decreased P3 amplitude compared to controls. It is concluded that among persons complaining of short-term memory disturbances, the individuals who show cerebral atrophy, taken as a group, have a P3 latency prolongation and/or low P3 amplitude a finding which reflects an impaired information processing.

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The diagnosis of Stargardt's disease, in cases of macular degeneration associated with neurological symptomatology, has been questioned. A 23 year old man, suffering from well characterized Stargardt's disease since childhood, presented with progressive spastic tetraparesis and cerebellar involvement since the age of 18. The case is presented and the association between the two clinical pictures is discussed.

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Platelet monoamine oxidase (MAO) and plasma dopamine-beta-hydroxylase (DBH) activities were determined in a large group of multiple sclerose patients in relapse (49 patients) and in remission (28 patients), and compared with an age- and sex-matched control group (52 normal subjects). The activities of both enzymes did not differ from normal in both patient groups. Women had higher MAO activities both in normal and in patient groups. Multiple linear regression analysis revealed an association of low platelet MAO to the score in the mental subscale in the Kurtzke Disability Status Scale. Both male and female patients with mental symptomatology had significantly (p = 0.02) lower platelet MAO activities compared to the patients without. The possibility of a relationship between MAO activity and psychiatric vulnerability in MS is considered.

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Monocytes from patients with multiple sclerosis (MS) express decreased numbers of class II major histocompatibility complex (MHC) antigens in peripheral blood and are poor stimulators in the autologous mixed lymphocyte reaction (autoMLR). We assessed the effect of prothymosin-alpha (ProT alpha) on the expression of MHC class II antigens by monocytes. Immediately after isolation, monocytes were analyzed for MHC class II antigen expression using a radiolabelled monoclonal antibody specific for a monomorphic determinant on HLA-DR antigens. After incubation with ProT alpha we observed significant increases in HLA-DR antigens on MS monocytes (1.5- to 4-fold increase compared to freshly isolated monocytes). Kinetic analysis revealed that enhancement peaked after 2 days of incubation with ProT alpha. The increase in HLA-DR antigen on MS monocytes resulted in the restoration of the deficient autoMLR in MS patients. This is the first demonstration suggesting a link between HLA-DR antigen expression and cellular immune defects in MS. The significance of low autoMLR responses for T suppressor levels in MS patients is discussed.

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Platelet serotonin uptake was studied in 20 patients with multiple sclerosis (MS) in acute relapse and in 20 age- and sex-matched controls. While there was no difference in the maximum velocity of the uptake, Michaelis constants were significantly higher and correlated positively with the Disability Status Scale score. The results suggest a competitive block of the serotonin uptake sites in platelets of MS patients.

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