Constantinos Sfagos

Associations of the Expanded Disability Status Scale with anxiety and depression in multiple sclerosis outpatients

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‐β in outpatients with relapsing–remitting multiple sclerosis (RRMS) during a clinically stable phase of their illness.

Increased plasma homocysteine levels in patients with multiple sclerosis and depression

BackgroundThe aim of the study was to assess the plasma levels of homocysteine in patients with multiple sclerosis (MS) and to investigate whether an association with depression exists.MethodsPlasma homocysteine (Hcy), vitamin B12 and plasma folate were measured in 65 moderately disabled patients with relapsing/remitting MS (RR-MS) and 60 healthy controls. All subjects were assessed with the Beck Depression Inventory (BDI).ResultsHcy levels were significantly increased in MS patients compared to controls (13.5 ± 4.7 μmol/l vs 8.5 ± 3.1, p < 0.001). A significant correlation was found between Hcy levels and BDI scores (Pearson r = 0.3025, p < 0.05). Plasma Hcy was not related to Extended Disability Status Scale (EDSS) score, age, disease duration or vitamin B12 and folate.ConclusionModerately disabled MS patients with elevated Hcy levels are particularly prone to develop depressive symptomatology. Further study is warranted in order to elucidate the prognostic and therapeutic implications of this novel finding.

Occipital neuralgia as an isolated symptom of C2 myelitis.

Occipital neuralgia has been attributed to lesions at a peripheral nerve or radicular level. On rare occasions, it has been associated with cervical cord lesions. We report a 55‐year‐old woman who presented with an isolated occipital neuralgia and was found on further investigation to have a restricted, isolated myelitis at C2 level. This represents the second reported case of occipital neuralgia due to C2 myelitis and should alert clinicians to considering cervical MRI in patients with occipital neuralgia.

Plasma homocysteine levels in patients with multiple sclerosis in the Greek population.

Background: In recent years, there has been increasing interest in the role of plasma homocysteine (Hcy) as a possible risk factor for several diseases of the central nervous system. The aim of this study was to determine the plasma levels of Hcy in a group of multiple sclerosis (MS) patients from a Greek population and the possible correlation with age, disability status, activity or duration of disease, sex, and treatment. Methods: The MS group that was studied consisted of 46 patients and a total of 42 healthy individuals served as a control group. Plasma Hcy levels were determined by means of high‐performance liquid chromatography coupled with fluorescence detection, after precolumn derivatization with 4‐Fluoro‐7‐aminosulfonylbenzofurazan (ABD‐F). Results: Statistical analysis revealed that, in the MS patients, Hcy levels were not significantly different as compared to those in the controls. Men presented with higher Hcy levels than women in the MS group; however, age, disease subtype, disease duration, relapse rate, and Expanded Disability Status Scale score/Multiple Sclerosis Severity Score did not significantly affect Hcy levels in MS patients. Conclusion: The preliminary data suggest that Hcy levels were not elevated in our sample of Greek MS patients, which does not support previous findings of a significant correlation between elevated serum Hcy levels and MS. Further studies to establish a possible association between MS and Hcy levels in the context of different ethnic groups with different habits are needed.

Familial asymmetric distal upper limb amyotrophy (Hirayama disease): report of a Greek family.

Introduction:Hirayama disease is a rare nonprogressive, predominantly unilateral, juvenile distal upper limb amyotrophy that involves C7, C8, and Th1 innervated muscles. The etiology and pathogenesis of this focal amyotrophy is presently unknown. There is a debate as to whether Hirayama disease is an unusual neck flexion induced cervical myelopathy or an intrinsic motor neuron disease. Despite being a sporadic disorder, familial forms have been occasionally described, with either autosomal recessive or dominant inheritance. Case Series:We describe a 3-generation Greek family, with 4 members affected by a benign distal upper limb amyotrophy of long duration, reminiscent of Hirayama disease, suggesting an autosomal dominant inheritance pattern. Hypothesizing that this familial amyotrophy might be related to autosomal dominant distal spinal muscular atrophy type V(dSMA-V) that is characterized by prominent involvement of the distal upper extremities, we tested the index case for glycyl tRNA synthetase and Berardinelli-Seip congenital lipodystrophy (BSCL2) N88S and S90L gene mutations (by direct sequencing) that are involved in the development of dSMA-V phenotype. Despite the phenotypical similarity of this familial amyotrophy to dSMA-V, no missense mutation in the genes presently associated with it was detected. Conclusion:The reported family is the first in the literature with occurrence of Hirayama amyotrophy in 3 generations of a family. Considering that familial forms of Hirayama amyotrophy are uncommon, it could be assumed that they might represent a different subtype of the same disease having the same clinical features but different pathogenesis.

Body Mass Index in Multiple Sclerosis: Associations with CSF Neurotransmitter Metabolite Levels

Body weight and height of patients with relapsing-remitting multiple sclerosis (RRMS) or clinically isolated syndrome suggesting MS (CIS) in the age range 18 to 60 years (154 males and 315 females) were compared with those of subjects (146 males and 212 females) free of any major neurological disease. In drug-free patients, CSF levels of the metabolites of noradrenaline (MHPG), serotonin (5-HIAA), and dopamine (HVA), neurotransmitters involved in eating behavior, were estimated in searching for associations with body mass index (BMI). Statistical evaluations were done separately for males and females. Lower BMI was found in female MS patients compared to female controls, more pronounced in RRMS. BMI was not associated with duration of illness, smoking, present or previous drug treatment, or disability score. Body height showed a shift towards greater values in MS patients compared to controls. Patients in the lower BMI quartile (limits defined from control subjects) had lower 5-HIAA and HVA compared to patients in the upper quartile. The results provide evidence for weight reduction during disease process in MS, possibly related to deficits in serotoninergic and dopaminergic activities that develop during disease course, resulting in impairments in food reward capacity and in motivation to eat.

Benign Raeder Syndrome Evolving Into Indomethacin-Responsive Hemicranial Headache

Benign Raeder syndrome is characterized by a self‐limiting unilateral continuous headache associated with ipsilateral ptosis, miosis, and frequently, facial hypohydrosis. Hemicrania continua is a chronic, strictly unilateral continuous headache associated with ipsilateral cranial autonomic symptoms. We report a 50‐year‐old man who presented with benign Raeder syndrome, which evolved into an indomethacin‐responsive hemicranial headache that resembled hemicrania continua.

Cerebrospinal fluid tau protein is increased in neurosyphilis: a discrimination from syphilis without nervous system involvement?

Objective: The objective of this study was to investigate the levels of &tgr; protein in neurosyphilis. Study Design: Total &tgr; protein in the cerebrospinal fluid of 12 patients with neurosyphilis, 17 with syphilis without nervous system involvement, 14 controls, and 14 patients with Alzheimer disease of comparable age were analyzed. Double-sandwich enzyme-linked immunosorbent assay was used for measurements. Results: Increased levels of cerebrospinal fluid total &tgr; were observed in neurosyphilis (median [25th–75th percentile]: 349 pg/mL [312–429]) and in Alzheimer disease (543 [441–1017]) as compared with the controls (189 [106–220]) and syphilis without nervous system involvement (190 [160–223]). Using a cutoff level of 300 pg/mL, increased &tgr; discriminated cases of neurosyphilis from syphilis without nervous system involvement with a sensitivity and specificity of 83% and 94%, respectively. Conclusions: These results indicate that increased total &tgr; may be useful in the discrimination of neurosyphilis from syphilis without nervous system involvement.

The rs10492972 KIF1B polymorphism and disease progression in Greek patients with multiple sclerosis

A recent genome-wide association study (GWAS) demonstrated an association of the rs10492972[C] variant of KIF1B with multiple sclerosis (MS) [1]. KIF1B encodes a kinesin superfamily member involved in mitochondrial axonal transport and may influence the ability of oligodendrocytes to remyelinate demyelinated axons [2, 3]. Impaired mitochondrial transport and chronic demyelination have been linked to axonal loss, which is important in the development of irreversible disability in MS [2, 4]. We therefore sought to investigate a possible influence of rs10492972 on disease progression in Greek MS patients. We studied 609 patients with MS [5]. Demographic and clinical data are shown in the table. Expanded disability status scale (EDSS) was measured in remission [6]. A total of 243 patients received disease-modifying therapy. MS severity score (MSSS) was determined in 562 patients (disease duration[1 year) [7]. The control group consisted of 230 healthy subjects (mean age 38.1 ± 10.7 years, 121 women). Patients and controls gave written informed consent for molecular genetic studies. DNA was isolated from peripheral blood using standard NaCl extraction. Genotyping of rs10492972 was performed with a standard PCR protocol (primers: 50 GGATACAAGGGGTGGTGA 30, 50 AAGTTATGTGGCCAGGA 30). MboII restriction of the 112-bp product resulted in Tand C-alleles (T-allele: 67 and 45-bp products; C-allele: 112-bp product). Statistical comparisons between patients and controls and between patients with different genotypes were performed using Chi-square, ANOVA, Mann–Whitney, and Kruskal–Wallis tests, as appropriate. Kaplan–Meier analysis (log-rank test) was used to assess the effect of genotypes on time to sustained disability. Analysis was performed with SPSS software. Genotype distribution in patients and controls was in Hardy–Weinberg equilibrium (p = 0.31 and 0.65). C-allele frequency was 0.31 in both patients and controls. There was no difference in allelic or genotype frequencies between patients and controls (p = 0.99 and 1.0). MSSS and time to EDSS 4.0 (Fig. 1) or 6.0 were not significantly

The Onset of Multiple Sclerosis in Greece: A Single-Center Study of 1,034 Consecutive Patients

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.