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BACKGROUND Hereditary angioedema (HAE) related to C1 esterase-inhibitor deficiency activates the classic complement pathway and results to edematous crises. Although HAE is usually associated with multiple immunoregulatory disorders,... more
BACKGROUND Hereditary angioedema (HAE) related to C1 esterase-inhibitor deficiency activates the classic complement pathway and results to edematous crises. Although HAE is usually associated with multiple immunoregulatory disorders, neurologic manifestations are rare. CASE REPORT We report on the case study of a 33-year-old man diagnosed with HAE (SERPIN1G gene mutation) and multiple sclerosis (MS), followed up for at least 6 years. After a first clinical attack of HEA with scrotal edema, MS disease exacerbation was observed. Treatment with glatiramer acetate could not prevent either MS or HAE clinical attacks with recurrent exacerbations been observed. Remission of MS and significant amelioration of HAE attacks were achieved under fingolimod treatment. CONCLUSIONS Herein we provide long term evaluation of an extremely rare case of concomitant existence of HAE and MS and present the effects of MS current disease-modifying therapies in HAE attacks. Our case highlights the possible effect of fingolimod in immunoregulatory-mechanisms implicated in both diseases.
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Background Baló’s Concentric Sclerosis (BCS) is a rare heterogeneous demyelinating disease with a variety of phenotypes on Magnetic Resonance Imaging (MRI). Existing literature lacks data especially on the therapeutic approach of the... more
Background Baló’s Concentric Sclerosis (BCS) is a rare heterogeneous demyelinating disease with a variety of phenotypes on Magnetic Resonance Imaging (MRI). Existing literature lacks data especially on the therapeutic approach of the disease which we intended to elucidate by means of suggesting a new possible BCS classification and introducing different therapeutic concepts based on each BCS-subgroup characteristics. Methods We present a retrospective study of eight treated patients with BCS-type lesions, emphasizing on MRI characteristics and differences on therapeutic maneuvers. Results Data analysis showed: at disease onset the BCS-type lesion was tumefactive (size ≥2 cm) in 6 patients, with a mean size of 2.7 cm (± 0.80 SD); a coexistence of MS-like plaques on brain MRI was identified in 7 patients of our cohort. The mean age was 26.3 years (±7.3 SD) at disease onset and the mean follow-up period was 56.8 months (range 9–132 months). According to radiological characteristics and...
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Aims:Our goal was to expand the spectrum of clinico-radiologic characteristics and the possible therapeutic choices in patients with tumefactive demyelinating lesions (TDLs).Methods:A retrospective analysis of 50 patients with at least... more
Aims:Our goal was to expand the spectrum of clinico-radiologic characteristics and the possible therapeutic choices in patients with tumefactive demyelinating lesions (TDLs).Methods:A retrospective analysis of 50 patients with at least one TDL was performed at an academic neurology center (2008–2020).Results:Our cohort comprised mostly women (33/50) with a mean age of 38 years at TDL onset. The mean follow-up time was 76 months. The mean Expanded Disability Status Scale score at TDL onset and at the latest neurological evaluation was 3.7 and 2.3, respectively. We subcategorized the patients into seven groups based mainly on the clinical/radiological findings and disease course. Group A included patients presenting with a Marburg-like TDL ( n = 4). Groups B and C comprised patients presenting with monophasic ( n = 7) and recurrent TDLs ( n = 12), respectively. Multiple sclerosis (MS) patients who subsequently developed TDL ( n = 16) during the disease course were categorized as Group...
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We aimed to determine whether Alemtuzumab-induced immune reconstitution affects immunoglobulin and complement levels in the serum of Relapsing-Remitting Multiple Sclerosis (RRMS) patients. IgG4-levels were increased 24-months after... more
We aimed to determine whether Alemtuzumab-induced immune reconstitution affects immunoglobulin and complement levels in the serum of Relapsing-Remitting Multiple Sclerosis (RRMS) patients. IgG4-levels were increased 24-months after treatment initiation compared to baseline levels in twenty-nine patients. Alemtuzumab-treated patients with the highest IgG4-levels were more prone to thyroid-related autoimmune manifestations and specific autoimmune adverse events such as Crohn's disease, Graves' disease, and hemolytic anemia. Compared to baseline, total IgG-levels showed a trend towards reduced levels following two-courses of Alemtuzumab, but no significant change of C3 and/or C4-levels was observed. In conclusion, monitoring of IgG4-levels can serve as a marker for secondary autoimmunity risk in multiple sclerosis patients treated with Alemtuzumab.
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Neuromyelitis optinca (NMO) represents a serious demyelinating disease of the central nervous system selectively attacking the spinal cord and optic nerve. Early differential diagnosis from multiple sclerosis is of vital importance, as... more
Neuromyelitis optinca (NMO) represents a serious demyelinating disease of the central nervous system selectively attacking the spinal cord and optic nerve. Early differential diagnosis from multiple sclerosis is of vital importance, as NMO mandates immunosuppressive and not immunomodulatory treatment. Rituximab has been recently introduced as a treatment option for NMO. However, optimal surrogate measures and treatment intervals are still unclear. Five patients (females, mean age 54±10.21years) with NMO and NMO spectrum disorders (NMOSD) were evaluated with respect to disability and relapse rate. All patients were found positive for NMO IgG. All patients (three with NMO and two with NMOSD, 1 patient with recurrent optic neuritis and 1 patient with recurrent myelitis) had received rituximab treatment for six years. One patient with NMOSD received cyclophosphamide prior to rituximab while two were misdiagnosed as multiple sclerosis and had received interferon treatment. All received rituximab infusion of 375mg/m2 once per week for 4weeks and then every two months for the first two years and then every six months. B-cell counts were measured every two months and were kept in almost undetectable levels. No relapse was noted during the treatment period while EDSS score was improved in all patients. No severe adverse effects occurred during RTX treatment. Rituximab treatment on NMO and NMOSD patients showed significant improvement in disability and relapse-rate without any significant adverse effects.
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ObjectiveThe polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding... more
ObjectiveThe polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome‐wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases.MethodsWe assembled an independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and genotyped single‐nucleotide polymorphisms (SNPs) selected from the most significant hits in the HD study.ResultsIn the analysis of DNA repair genes ...
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AimsBladder dysfunction is frequent during the course of multiple sclerosis (MS), observed in up to 75% of patients. Urinary symptomatology can be a feature of the first episode of MS in a minority of cases, and most often shows... more
AimsBladder dysfunction is frequent during the course of multiple sclerosis (MS), observed in up to 75% of patients. Urinary symptomatology can be a feature of the first episode of MS in a minority of cases, and most often shows characteristics of an overactive bladder (OAB), with voiding symptoms seen less frequently, often in combination with OAB. The neural control of micturition is complex, involving systems located in the brain, spinal cord, and periphery, and implicating central noradrenergic, serotonergic, and dopaminergic activities. Urinary disorders are also linked to anxiety and depression, conditions connected to hypothalamus–pituitary–adrenal axis activity. In this study we aimed to investigate neurochemical and neuroendocrine correlates of bladder dysfunction in early MS.MethodsWe included 101 patients at first demyelinating episode suggestive of MS that were drug‐free at assessment. We evaluated the presence of urinary symptomatology and estimated CSF levels of the ma...
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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.... more
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...
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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... more
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...
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Several studies have investigated leptin levels in patients with multiple sclerosis (MS) with somewhat conflicting results. They have all focused on patients with established relapsing-remitting (RR) MS but have not specifically looked at... more
Several studies have investigated leptin levels in patients with multiple sclerosis (MS) with somewhat conflicting results. They have all focused on patients with established relapsing-remitting (RR) MS but have not specifically looked at patients with clinically isolated syndrome (CIS) suggestive of MS, in the early stages of disease. In this study, serum leptin levels were measured in 89 treatment-naïve patients with CIS (53 patients) or RRMS (36 patients) and 73 controls searching for differences between the groups and for associations with several disease parameters. The expected significant sexual dimorphism in leptin levels (higher levels in females) was observed in both MS patients and controls. Increased leptin levels were found in female patients with RRMS compared to female controls (P=.003) and female CIS patients (P=.001). Female CIS patients had comparable levels to controls. Leptin levels correlated positively to disease duration, but not to EDSS, in female patients wi...
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Research Interests: Multiple sclerosis, Incidence Geometry, Biology, Medicine, Serotonin, and 15 moreHumans, Internal Medicine, Correlation, Aggression, Cholesterol, Female, Male, Clinically isolated syndrome, Central Nervous System, Middle Aged, Adult, Sex Characteristics, lumbar puncture, Psychology and Cognitive Sciences, and Medical and Health Sciences
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Research Interests: Multiple sclerosis, Cognition, Medicine, Comorbidity, Greece, and 15 moreBrain, Humans, Female, Male, Clinically isolated syndrome, Clinical Sciences, Middle Aged, Cognitive impairment, Adult, Learning Disorders, Age Factors, Memory Disorders, Cognition disorders, Neuropsychological Tests, and Disability Evaluation
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Crying as a response to emotionally-charged situations varies greatly among individuals, genders, and cultures. Information on the neural systems involved in crying behavior comes mainly from studies of pathological laughing and crying in... more
Crying as a response to emotionally-charged situations varies greatly among individuals, genders, and cultures. Information on the neural systems involved in crying behavior comes mainly from studies of pathological laughing and crying in patients after brain injury. The authors assessed crying proneness (CPR) as expressed by the score on the "crying easily" item of the SCL-90 questionnaire in 65 men and 105 women subjects in whom lumbar puncture was performed for diagnostic reasons. None of the subjects showed pathological laughing or crying. The authors estimated the levels of the main metabolites of noradrenaline (MHPG), serotonin (5-HIAA), and dopamine (HVA) in CSF, and searched for associations to CPR score. Subjects with high CPR showed significantly lower MHPG levels than subjects with low CPR, and no differences in 5-HIAA or HVA levels. Higher frequencies of women were found in the subgroups with high CPR. The "crying easily" score was positively associated with the Interpersonal Sensitivity subscale of the SCL-90 questionnaire in female but not in male subjects, indicating the cultural dimension of crying behavior, while it was not associated with the Depression subscale score. It is suggested that central noradrenergic mechanisms control the threshold for tear production in normal crying behavior.
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Research Interests: Endocrinology, Multiple sclerosis, Neuroendocrinology, Adolescent, Medicine, and 15 moreCerebrospinal Fluid, Humans, Prolactin, Internal Medicine, Female, Male, Clinically isolated syndrome, Clinical Sciences, Middle Aged, Adult, Remyelination, Neurosciences, Case Control Studies, Demyelinating diseases, and relapsing remitting multiple sclerosis
Axonal degeneration and brain tissue loss occur during disease progression in multiple sclerosis (MS) and are expected to influence neurotransmitter activities, with consequences on neurologic and psychiatric symptomatology. We searched... more
Axonal degeneration and brain tissue loss occur during disease progression in multiple sclerosis (MS) and are expected to influence neurotransmitter activities, with consequences on neurologic and psychiatric symptomatology. We searched for relationships of disease duration, disability, and severity of MS patients to CSF levels of the major metabolites of noradrenaline, dopamine, and serotonin, MHPG, methoxyhydroxyphenylglycol (MHPG), homovanillic acid, and 5‐hydroxyindoleacetic acid (5‐HIAA), respectively, in 39 patients with relapsing–remitting (RR) MS in remission, and 26 patients with progressive (PR) MS. Disability and Disease Severity were assessed by the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). Compared with the levels of 50 control subjects, MHPG levels were not different in either MS group, correlated negatively to duration of illness and number of relapses in the RRMS group, but not to EDSS score or to MSSS. Homovanillic aci...
Research Interests: Psychology, Multiple sclerosis, Neurochemistry, Adolescent, Medicine, and 15 moreDopamine, Humans, Internal Medicine, Female, Male, Regression Analysis, Young Adult, Disease Severity, Middle Aged, Adult, Disease Progression, Neurotransmitter, Neurosciences, Severity of Illness Index, and Disability Evaluation
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... more
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.
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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... more
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 ...