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Introduction Short cognitive screening instruments (CSIs) are widely used to stratify patients presenting with cognitive symptoms. The Quick Mild Cognitive Impairment (Qmci) screen is a new, brief ( Methods Consecutive patients aged ≥55 years presenting with cognitive complaints were recruited from two outpatient clinics in Greece. All patients completed the Qmci-Gr and SMMSE and underwent an independent detailed neuropsychological assessment to determine a diagnostic classification. Results In total, 140 patients, median age 75 years, were included; 30 with mild dementia (median SMMSE 23/30), 76 with MCI and 34 with subjective memory complaints (SMC) but normal cognition. The Qmci-Gr had similar accuracy in differentiating SMC from cognitive impairment (MCI & mild dementia) compared with SMMSE, area under the curve (AUC) of 0.84 versus 0.79, respectively; while accuracy was higher for the Qmci-Gr, this finding was not significantly different, (p = .19). Similarly, the Qmci-Gr had similar accuracy in separating SMC from MCI, AUC of 0.79 versus 0.73 (p = .23). Conclusions The Qmci-Gr compared favorably with the SMMSE. Further research with larger samples and comparison with other instruments such as the Montreal Cognitive Assessment is needed to confirm these findings but given its established brevity, it may be a better choice in busy clinical practice in Greece.

We investigated: (i) the cognitive performance of type 2 diabetes mellitus (T2DM) patients compared to healthy control participants and (ii) the Health-related Quality of life (HRQOL) of type 2 diabetics with neuropsychological deficits.We conducted a prospective study in (N = 44) T2DM patients and (N = 28) demographically matched healthy controls. All participants were assessed with a flexible comprehensive neuropsychological battery of tests that have been standardized in Greece and found to be sensitive in detecting cognitive deficits in type 2 diabetics. They were additionally assessed on measures of general intelligence, general mental state, and depression. They were also administered the WHO QOL-BREF self-report questionnaire to evaluate perceived health-related quality of life.Groups were well matched on baseline demographic characteristics and estimated premorbid intelligence. The groups did not differ on general mental state but varied in the encoding of verbal material, total verbal learning, delayed recall of verbal information, mental information processing speed, phonological and semantic verbal fluency and executive functions, set-shifting. Glycosylated hemoglobin levels and an interaction of age, education, and premorbid intelligence were the most important predictors of domain-specific neuropsychological performance. T2DM patients with deficits in verbal learning, executive functions, set-shifting, and semantic verbal fluency, had significantly lower QOL in the domains of psychological and environmental health, social relationships, and general health, respectively.T2DM patients have cognitive deficits on several domains compared to healthy participants. Domain specific neuropsychological deficits in middle aged T2DM patients have a significant impact on HRQOL.

Objective: We investigated: (i) the cognitive performance of type 2 diabetes mellitus (T2DM) patients compared to healthy control participants and (ii) the Health-related Quality of life (HRQOL) of type 2 diabetics with neuropsychological deficits.

About half of patients with multiple sclerosis exhibit cognitive impairment which negatively affects their quality of life. The assessment of cognitive function in routine clinical practice is still undervalued, although various tools have been proposed for this reason. In this article, we describe the potential benefits of implementing cognitive assessment tools in routine follow -ups of MS patients. Early detection of changes in cognitive performance may provide evidence of disease activity, could unmask depression or medication side-effects and provide suitable candidates for cognitive rehabilitation. Since apathy and cognitive deficiencies are common presenting symptoms in Progressive Multifocal Leukoencephalopathy, we discuss the utility of frequent monitoring of mental status in multiple sclerosis patients at increased risk. In addition, we propose a relevant algorithm aiming to incorporate a systematic evaluation of cognitive function in every day clinical practice in multiple sclerosis.

Objective:The objective of this study was to investigate the pattern and severity of cognitive and language impairment in Greek patients with Relapsing-remitting (RRMS) and Secondary Progressive Multiple Sclerosis (SPMS), relative to control participants.Method:A prospective study was conducted in 27 patients with multiple sclerosis (PwMS), (N= 15) with RRMS, (N= 12) with SPMS, and (N= 12) healthy controls. All participants were assessed with a flexible comprehensive neuropsychological – language battery of tests that have been standardized in Greece and validated in Greek MS patients. They were also assessed on measures of disability (Expanded Disability Status Scale; EDSS), fatigue (Fatigue Severity Scale; FSS) and depression (Beck Depression Inventory - fast screen; BDI-FS).Results:Our results revealed that groups were well matched on baseline demographic and clinical characteristics. The two clinical groups (RRMS; SPMS) did not differ on overall global cognitive impairment but differed in the initial encoding of verbal material, mental processing speed, response inhibition and set-shifting. RRMS patients differed from controls in the initial encoding of verbal material, learning curve, delayed recall of verbal information, processing speed, and response inhibition. SPMS patients differed in all utilized measures compared to controls. Moreover, we noted increased impairment frequency on individualized measures in the progressive SPMS group.Conclusion:We conclude that MS patients, irrespective of clinical subtype, have cognitive deficits compared to healthy participants, which become increasingly worse when they convert from RRMS to SPMS.On the contrary,the pattern of impairment remains relatively stable.

Recent studies by Bastiaanse and colleagues found that time reference is selectively impaired in people with nonfluent agrammatic aphasia, with reference to the past being more difficult to process than reference to the present or to the future. To account for this dissociation, they formulated the PAst DIscourse LInking Hypothesis (PADILIH), which posits that past reference is more demanding than present/future reference because it involves discourse linking. There is some evidence that this hypothesis can be applied to people with fluent aphasia as well. However, the existing evidence for the PADILIH is contradictory, and most of it has been provided by employing a test that predominantly taps retrieval processes, leaving largely unexplored the underlying ability to encode time reference-related prephonological features. Within a cross-linguistic approach, this study tests the PADILIH by means of a sentence completion task that 'equally' taps encoding and retrieval abilities. This study also investigates if the PADILIH’s scope can be extended to fluent aphasia. Greek- and Italian-speaking individuals with aphasia participated in the study. The Greek group consisted of both individuals with nonfluent agrammatic aphasia and individuals with fluent aphasia, who also presented signs of agrammatism. The Italian group consisted of individuals with agrammatic nonfluent aphasia only. The two Greek subgroups performed similarly. Neither language group of participants with aphasia exhibited a pattern of performance consistent with the predictions of the PADILIH. However, a double dissociation observed within the Greek group suggests a hypothesis that may reconcile the present results with the PADILIH.

Cognitive impairment is frequently encountered in multiple sclerosis (MS) affecting between 40–65% of individuals, irrespective of disease duration and severity of physical disability. In the present multicenter randomized controlled trial, fifty-eight clinically stable RRMS patients with mild to moderate cognitive impairment and relatively low disability status were randomized to receive either computer-assisted (RehaCom) functional cognitive training with an emphasis on episodic memory, information processing speed/attention, and executive functions for 10 weeks (IG; n=32) or standard clinical care (CG; n=26). Outcome measures included a flexible comprehensive neuropsychological battery of tests sensitive to MS patient deficits and feedback regarding personal benefit gained from the intervention on four verbal questions. Only the IG group showed significant improvements in verbal and visuospatial episodic memory, processing speed/attention, and executive functioning from pre - to postassessment. Moreover, the improvement obtained on attention was retained over 6 months providing evidence on the long-term benefits of this intervention. Group by time interactions revealed significant improvements in composite cognitive domain scores in the IG relative to the demographically and clinically matched CG for verbal episodic memory, processing speed, verbal fluency, and attention. Treated patients rated the intervention positively and were more confident about their cognitive abilities following treatment.

Objectives The purpose of this study was to generate normative data on the Symbol Digits Modalities Test (SDMT) for the written and oral versions in the Greek adult population. We also investigated the test’s validity in discriminating the performance of healthy adults from two groups of adults diagnosed with relapsing remitting (RRMS) and secondary progressive (SPMS) multiple sclerosis. Method The sample consisted of 609 healthy men and women between the ages of 18 and 65. All participants were monolingual native Greek adult speakers. Each healthy participant was administered either the written (n = 460) or oral (n = 149) versions of the SDMT. Discriminant validity was examined by comparing 35 healthy participants who had completed the oral version of the SDMT to 35 age - and education-matched RRMS and SPMS patients. Results Linear regression models explained between 36% and 55% of the variance in the SDMT oral and written version scores. Age was the strongest predictor of difference in SDMT written and oral version performance, followed by education that also accounted for a further proportion of the SDMT variance. On the contrary, gender was found not to contribute significantly to the variance in the SDMT for either the written or the oral versions. As a result, age- and education-adjusted norms were generated. Regarding the tests discriminative validity, we found that both MS patient groups scored significantly lower than the healthy group. Conclusions This is the first study to provide comprehensive normative data for the SDMT in the adult population in Greece, impacting the future practice of neuropsychological assessment in this country.

Objective: Given the underlying frontal-basal ganglia circuit neuropathogenesis of HIV-infected individuals, it is surprising that little is reported about potential language deficits as part of their higher cognitive dysfunctional profile. This study aims to elucidate whether HIV-positive individuals have linguistic impairments that may originate from or be intensified by deficits in cognitive functions. The research questions address (i) quantitative differences in sentence repetition abilities involving complex syntactic phenomena between adults with HIV and non-HIV healthy controls (ii) correlations of sentence repetition scores with neurocognitive measures and (iii) correlation of sentence repetition performance with duration and severity of HIV. Methods: A battery of neuropsychological tests were administered to 40 HIV - seropositive males and 40 demographically matched healthy controls to assess verbal learning/episodic memory, psychomotor speed, executive functions and visuospatial abilities. Language abilities were evaluated using a repetition task that screened specific complex syntactic operations at the sentence-level. Results: A significant difference was noted between the two groups regarding correct repetition of the sentence repetition task with the control group outperforming the HIV-seropositive group. For the HIV group, significant correlations were found for correct sentence repetition with years of education, duration of illness, Mini-Mental State Examination, semantic and phonemic fluency, symbol digit modality test scores, and the Trail Making Test (parts A and B). Conclusion: Speech-language pathologists and neuropsychologists should screen for language deficits associated with the different clinical syndromes in HIV patients as part of their routine clinical care.

Objectives Increasing observational evidence on the biological effects of Space Weather suggests that geomagnetic disturbances may be an environmental risk factor for multiple sclerosis (MS) relapses. In the present study, we aim to investigate the possible effect of geomagnetic disturbances on MS activity. Patients and methods MS patient admittance rates were correlated with the solar and geophysical data covering an eleven-year period (1996–2006, 23rd solar cycle). We also examined the relationship of patterns of the solar flares, the coronal mass ejections (CMEs) and the solar wind with the recorded MS admission numbers. Results The rate of MS patient admittance due to acute relapses was found to be associated with the solar and geomagnetic events. There was a “primary” peak in MS admittance rates shortly after intense geomagnetic storms followed by a “secondary” peak 7–8 months later. Conclusion We conclude that the geomagnetic and solar activity may represent an environmental health risk factor for multiple sclerosis and we discuss the possible mechanisms underlying this association. More data from larger case series are needed to confirm these preliminary results and to explore the possible influence of Space Weather on the biological and radiological markers of the disease.

Cognitive impairment is common in multiple sclerosis (MS), but deficits tend to be more pronounced in progressive MS, negatively impacting daily functional capacity. Despite this, most cognitive rehabilitation (CR) interventions to date have focused on relapsing-remitting MS (RRMS). Moreover, information on the efficacy of CR in progressive MS is limited and controversial. The present study investigated the efficacy of a home based, computer assisted cognitive rehabilitation (HBCACR) intervention (RehaComThis was a randomized, multi site, sham controlled trial. Thirty six (36) individuals with SPMS, naïve to the RehaCom software, with cognitive deficits were randomized to the treatment (IG; n= 19) or control group condition (CG; n=17). Treatment with the RehaCom modules consisted of 24 domain and task specific, 45 minute session's over an 8-week period, three sessions per week, applied by each patient at home. The CG completed non specific computer based activities at home with the same frequency and duration. Primary cognitive outcome measures included the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, and secondary outcome measures for depression (BDI-FS), fatigue (MFIS), and quality of life (EuroQol EQ-5D) visual analogue scale (VAS).The two groups were well matched on demographic and clinical characteristics, cognitive reserve and severity of cognitive deficits at baseline assessment. At post treatment assessment the IG group showed significant improvements with large effect sizes; in verbal learning [z = -4.759, p.0005, g = 2.898], visuospatial memory [z = -3.940, p.0005, g = 1.699] and information processing speed [z= -4.792, p.0005, g = 2.980], compared with the sham control group. We also found significant between group differences on physical [z=-3.308, p = .001, g= -.604], cognitive [z = -4.011, p.0005, g = -1.654], psychosocial [z= 3.308, p = .010, g = -.940], and general fatigue impact [z= -2.623, p = .008, g = -.519], depression severity [z = -2.730, p = .006, g = -.519], and quality of life [z= -4.239, p.0005, g = -1.885] in favor of the treated group.These data provide the first evidence supporting the efficacy of computer based restorative cognitive rehabilitation applied at home exclusively in SPMS patients, suggesting that adaptive neuroplasticity may occur after functional cognitive training in progressive MS. Improved cognitive functioning in combination with mood augmentation appear to have ameliorated fatigue, which impacted daily functioning activity and culminated in improved health related quality of life.

Introduction Cognitive impairment is an important predictor of quality of life at all stages of MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. Objective The aim of the study was to designate the MRI marker that predicts cognitive decline and explore its effect on every day activities and employment status. Methods 50 RRMS patients and 31 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Everyday activities were evaluated with the instrumental activities of daily living (IADL) scale and employment status. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, corpus callosum and thalamic atrophy. Results The frequency of cognitive dysfunction for our RRMS patients was 38%. RRMS patients differed significantly from controls on the TMTA, TMTB, phonological verbal fluency task, memory, psychomotor speed, reaction time and cognitive flexibility. Neuropsychological measures had a strong correlation with all MRI atrophy measures and a weak or moderate correlation with lesion volume. Psychomotor speed was the most sensitive marker for IADL, while memory and TMTB for employment status. Thalamic area was the most sensitive MRI marker for memory, psychomotor speed and TMTB.. Conclusion Thalamic atrophy predicts the clinically meaningful cognitive decline in our RRMS patients.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system, and it has been established that autoreactive T helper (Th) cells play a crucial role in its pathogenesis. Myelin basic protein (MBP) epitopes are major autoantigens in MS, and the sequence MBP87-99 is an immunodominant epitope. We have previously reported that MBP87-99 peptides with modifications at principal T-cell receptor (TCR) contact sites suppressed the induction of EAE symptoms in rats and SJL/J mice, diverted the immune response from Th1 to Th2 and generated antibodies that did not cross react with the native MBP protein. In this study, the linear and cyclic analogs of the MBP87-99 epitope, namely linear (Ala91,Ala96)MBP87-99 (P2) and cyclo(87-99)(Ala91,Ala96)MBP87-99 (P3), were evaluated for their binding to HLA-DR4, stability to lysosomal enzymes, their effect on cytokine secretion by peripheral blood mononuclear cells (PBMC) derived from MS patients or healthy subjects (controls), and their effect in rat EAE. P1 peptide (wild-type, MBP87-99) was used as control. P2 and P3 did not alter significantly the cytokine secretion by control PBMC, in contrast to P1 that induced moderate IL-10 production. In MS PBMC, P2 and P3 induced the production of IL-2 and IFN-γ, with a simultaneous decrease of IL-10, whereas P1 caused a reduction of IL-10 secretion only. The cellular response to P3 indicated that cyclization did not affect the critical TCR contact sites in MS PBMC. Interestingly, the cyclic P3 analog was found to be a stronger binder to HLA-DR4 compared to linear P2. Moreover, cyclic P3 was more stable to proteolysis compared to linear P2. Finally, both P2 and P3 suppressed EAE induced by an encephalitogenic guinea pig MBP74-85 epitope in Lewis rats whereas P1 failed to do so. In conclusion, cyclization of myelin altered peptide ligand (Ala91,Ala96)MBP87-99 improved binding affinity to HLA-DR4, resistance to proteolysis and antigen-specific immunomodulation, rendering cyclo(87-99)(Ala91,Ala96)MBP87-99 an important candidate drug for MS immunotherapy.

Cognitive impairment in Multiple Sclerosis (MS) is more frequent and pronounced in secondary progressive MS (SPMS). Cognitive decline is an important predictor of employment status in patients with MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. The aim of the study was to designate the MRI marker that predicts cognitive decline in SPMS and explore its effect on employment status. 30 SPMS patients and 30 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Employment status was obtained as a quality of life measure. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, thalamic and corpus callosum atrophy. The frequency of cognitive decline for our SPMS patients was 80%. SPMS patients differed significantly from controls in all neuropsychological measures. Corpus callosum area was correlated with cognitive flexibility, processing speed, composite memory, executive functions, psychomotor speed, reaction time and phonological verbal fluency task. Processing speed and composite memory were the most sensitive markers for predicting employment status. Corpus callosum area was the most sensitive MRI marker for memory and processing speed. Corpus callosum atrophy predicts a clinically meaningful cognitive decline, affecting employment status in our SPMS patients.

Background: The last two decades have afforded a small but steady rise in the number of studies exposing language dysfunctions in patients with relapsing remitting multiple sclerosis (RRMS), the most common form of multiple sclerosis however, not much is known about word class naming deficits in this group of individuals.Aim: To explore whether individuals with RRMS show word class naming deficits favouring either nouns or verbs, and if verb accuracy is affected by semantic and phonological verb type.Method: A total of 31 adults with RRMS were compared to 28 demographically matched healthy controls on noun and verb production using the Greek Object and Action Test (GOAT), a picture-based assessment developed for this purpose. Different semantic categories of verbs were investigated such as conceptually/semantically heavy verbs (i.e., instrumental verbs, e.g., sweeping) compared to conceptually/semantically weaker verbs (i.e., non-instrumental verbs (NIVs), e.g., sleeping) and instrumental verbs that were phonologically related to a noun (i.e., name-related instrumental verbs, e.g., mopping).Outcome & results: Verbs were significantly more difficult to retrieve than nouns for the RRMS group on production tasks compared to the demographic and intelligence matched healthy participants. Moreover, there was a significant difference between instrumental and NIV production with instrumental verbs more difficult to retrieve than NIVs. In regard to phonological relatedness, non-name-related instrumental verbs were significantly more difficult to retrieve than name-related instrumental verbs. Multiple regression analyses conducted as a separate model for verbs and nouns indicated that performance on the GOAT could not be explained by any of the predictor variables (demographic, clinical, or neurocognitive performance).Conclusion: Based on the results, the grammatical distinction for Greek verbs and nouns seems to be preserved in this group of individuals with RRMS. The naming deficit is probably in the connection between the semantic lexicon and the phonological lexicon. In the case of verbs, the magnitude of the difficulty was larger because of the effects of word frequency on verb retrieval. Overall, poor performance on verb and noun naming may be a marker of incipient cognitive decline, and typical cognitive-linguistic testing is not sensitive or specific enough to capture this phenomenon. Refereed/Peer-reviewed

Background: Families of individuals with psychotic disorders are playing a major role in the care of their relatives, but report poorer physical competence, elevated symptoms of psychological distress and more psychopathological characteristics. Aim: To compare psychopathological characteristics demonstrated by caregivers of psychotic patients in Greece who participated in support groups organized by non-governmental mental health organizations (NGOMH) compared to caregivers who did not. Methods: Participants were caregivers of a psychotic patient assigned to either the intervention group ( n = 165) or the non-intervention group ( n = 345) according to specific criteria. Participants were assessed for psychopathological characteristics through clinical interviews and with the Symptom Checklist 90–Revised (SCL-90-R). Results: Participants who did not take part in the support groups had higher levels of psychopathological characteristics on the dimensions of interpersonal sensitivity ( t = −2.065, p = .003), depression ( t = 1.043, p = .007), anxiety ( t = 1.001, p = .010), hostility ( t = −4.345, p Conclusion: Participation in support groups and sharing of emotional expression, thoughts and ideas help the caregivers deal with their physical and psychological demands related to the caregiver load. As such, intervention strategies offered to caregivers in the support groups appear to positively contribute to the family with a psychotic patient and improve the quality of life of both patients and their main caregivers.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) of autoimmune etiology that results from an imbalance between CNS-specific T effector cells and peripheral suppressive mechanisms mediated by regulatory cells (RC). In this research, we collected blood samples from 83 relapsing remitting MS (RRMS) patients and 45 healthy persons (HC), to assess the sizes of their RC populations, including CD4⁺CD25(high)Foxp3⁺ (nTregs), CD3⁺CD4⁺HLA(-)G⁺, CD3⁺CD8⁺CD28(-), CD3⁺CD56⁺, and CD56(bright) cells, and how RC are affected by disease activity (acute phase or remission) and types of treatment (methylprednisolone, interferon, or natalizumab). In addition, we isolated peripheral blood mononuclear cells (PBMC) and cultured them with peptides mapping to myelin antigens, to determine RC responsiveness to autoantigens. The results showed decreased levels of nTregs in patients in the acute phase ± methylprednisolone and in remission + natalizumab, but HC levels in patients in remission or receiving interferon. Patients + interferon had the highest levels of CD3⁺CD4⁺HLA(-)G⁺ and CD3⁺CD8⁺CD28(-) RC, and patients in the acute phase + methylprednisolone the lowest. Patients in remission had the highest levels of CD3⁺CD56⁺, and patients in remission + natalizumab the highest levels of CD56(bright) cells. Only nTregs responded to autoantigens in culture, regardless of disease activity or treatment. The highest suppressive activity was exhibited by nTregs from patients in remission. In conclusion, in RRMS disease activity and type of treatment affect different RC populations. nTregs respond to myelin antigens, indicating that it is possible to restore immunological tolerance through nTreg induction.

Multiple sclerosis (MS), an autoimmune disease of the CNS, is mediated by autoreactive Th cells. A previous study showed that the neurosteroid dehydroepiandrosterone (DHEA), when administered preclinically, could suppress progression of relapsing-remitting experimental autoimmune encephalomyelitis (EAE). However, the effects of DHEA on human or murine pathogenic immune cells, such as Th17, were unknown. In addition, effects of this neurosteroid on symptomatic disease, as well as the receptors involved, had not been investigated. In this study, we show that DHEA suppressed peripheral responses from patients with MS and reversed established paralysis and CNS inflammation in four different EAE models, including the 2D2 TCR-transgenic mouse model. DHEA directly inhibited human and murine Th17 cells, inducing IL-10–producing regulatory T cells. Administration of DHEA in symptomatic mice induced regulatory CD4+ T cells that were suppressive in an IL-10–dependent manner. Expression of the estrogen receptor β by CD4+ T cells was necessary for DHEA-mediated EAE amelioration, as well as for direct downregulation of Th17 responses. TGF-β1 as well as aryl hydrocarbon receptor activation was necessary for the expansion of IL-10–producing T cells by DHEA. Thus, our studies demonstrate that compounds that inhibit pathogenic Th17 responses and expand functional regulatory cells could serve as therapeutic agents for autoimmune diseases, such as MS.

Background Although Fingolimod (FGD) and Natalizumab (NTZ) appear to be effective in relapsing-remitting multiple sclerosis (RRMS), they have never been directly compared in a randomized clinical trial (RCT). Methods and Findings We evaluated the comparative efficacy of FGD vs. NTZ using a meta-analytical approach. Data from placebo-controlled RCTs was used for indirect comparisons and observational data was utilized for head-to-head comparisons. We identified 3 RCTs (2498 patients) and 5 observational studies (2576 patients). NTZ was associated with a greater reduction in the 2-year annualized relapse rate (ARR; SMDindirect = -0.24;95% CI: from -0.44 to -0.04; p = 0.005) and with the probability of no disease activity at 2 years (ORindirect:1.82, 95% CI: from 1.05 to 3.15) compared to FGD, while no differences between the two therapies were found in the proportion of patients who remained relapse-free (ORindirect = 1.20;95% CI: from 0.84 to 1.71) and those with disability progression (ORindirect = 0.76;95% CI: from 0.48 to 1.21) at 2 years. In the analysis of observational data, we found no significant differences between NTZ and FGD in the 2-year ARR (SMD = -0.05; 95% CI: from -0.26 to 0.16), and 2-year disability progression (OR:1.08;95% CI: from 0.77 to 1.52). However, NTZ-treated patients were more likely to remain relapse-free at 2-years compared to FGD (OR: 2.19;95% CI: from 1.15 to 4.18; p = z0.020). Conclusions Indirect analyses of RCT data and head-to-head comparisons of observational findings indicate that NTZ may be more effective than FGD in terms of disease activity reduction in patients with RRMS. However, head-to-head RCTs are required to independently confirm this preliminary observation.

Episodic memory impairment is a robust correlate of familial risk for schizophrenia (SZ) and bipolar disorder (BD); still much is unknown about the processes that underlie this deficit and how they may be implicated in BD and SZ. We examined the possibility that (a) episodic memory impairment may arise from abnormalities in the cognitive control of interference between task-relevant and task-irrelevant memories during retrieval; inability to suppress task-irrelevant representations could give rise to intrusions of inappropriate memories and increased rate of forgetting, (b) cognitive control deficits during retrieval may be differentially affected by familial predisposition to SZ or BD. We examined episodic memory in relatives of patients with SZ (SZ-R) (n = 15) or BD (BD-R) (n = 17) compared to healthy controls (n = 23) using the California Verbal Learning Test (CVLT) and the Doors and People Test (DPT). All relatives were free of any psychiatric morbidity and were matched to controls on age, sex, educational achievement and general intellectual ability. During the CVLT, both relatives' groups made significantly more perseverative recall errors than controls. However, intrusion errors were significantly increased in SZ-R only. SZ-R also showed increased rate of forgetting in the DPT while BD-R were comparable to controls. Familial predisposition to SZ, compared to that of BD, was associated with significantly greater impairment in cognitive control processes during episodic memory retrieval with some evidence of specificity for SZ in connection with mechanisms relating to increased forgetting.

Functional single-nucleotide polymorphisms (SNPs) of inflammatory cytokines have been previously related to the occurrence of an ischemic stroke (IS). We investigated whether five functional SNPs (i.e., TNF-α-308G>A, IL6-174G>C, IL12B 1188A>C, IL4-589C>T, and IL10-1082G>A) might be associated with the age of onset and 6-month outcome of an acute IS. A probe-free real-time PCR methodology was used to genotype 145 consecutively admitted cases with a first-ever IS. Simple Kaplan-Mayer and adjusted Cox regression analyses showed no association between inflammatory genotypes and the age of IS onset. IL6-174G>C, IL12B 1188A>C, IL4-589C>T, and IL10-1082G>A were not found to significantly contribute to the long-term outcome of the disease. However, carriage of the TNF-α-308 GG genotype was significantly associated with reduced odds for an adverse outcome. Larger studies are needed to confirm our results.

We report a 40-year-old male patient with widespread chronic plaque psoriasis, who complained of distal numbness in the right leg with gradual proximal extension after 1 month of treatment with oral acitretin. Neurological examination showed suppressed ankle reflexes, reduced pain and vibration sense in a glove and stocking distribution, and mild weakness of feet dorsiflexion. Neurophysiologic examination revealed a shift of the amplitude of all sensory and compound muscle action potentials toward low values, whereas in the case of sural and popliteal nerves, the amplitude felt below reference limits. Follow-up examination of the patient 1 month after treatment discontinuation revealed no abnormal neurological symptoms or signs, whereas the values of the neurophysiologic measurements had returned to normal levels. The case of sensorimotor polyneuropathy presented herein underlines the necessity for detailed neurological and neurophysiologic examinations of patients before and during oral administration of acitretin.

Bone marrow transplantation (BMT) was introduced as a treatment option 15 years ago for severe, drug-resistant multiple sclerosis (MS). Up until now, BMT has been undertaken in relatively few patients worldwide, with moderate success, and recent studies suggest that patients with early, highly aggressive MS benefit most from this treatment. In this work, we determined peripheral blood lymphocyte populations in a patient (patient A) with remitting–relapsing multiple sclerosis (RR-MS), refractory to conventional treatments, and who underwent BMT, relapsed, and has been treated with natalizumab for the last 22 months. Eleven other RR-MS patients in the acute phase of the disease, untreated or treated with interferon-beta, and 20 healthy subjects served as controls. Natalizumab treatment in patient A resulted in lymphocytosis and increased levels of CD20+/CD20+CD5+ B cells and T regulatory cells (Tregs). The patient maintained relatively low levels of T cells, T helper cells, memory T helper cells, and naive cytotoxic T cells, and very low levels of naive T helper cells and natural killer cells throughout. The Tregs of patient A post-treatment with natalizumab responded well in culture to a peptide mapping to a myelin basic protein antigenic epitope (mean 42% increase) compared with Tregs of healthy controls (mean 15% increase) whereas Tregs of the RR-MS controls or patient A prenatalizumab treatment either did not respond or responded adversely to the peptide (mean 3% and 21% decreases, respectively). Since the beginning of natalizumab treatment, patient A has had no relapses, and his Expanded Disability Status Score has improved. From the parameters studied, Treg responsiveness to autoantigens seems to be an important differentiating factor in RR-MS progression.

Background and purpose: Inflammatory cytokines are involved in the systemic inflammation, which precedes an ischaemic stroke (IS), and also participate into brain ischaemia-reperfusion injury. We sought to investigate whether functional polymorphisms of two anti-inflammatory molecules, interleukin (IL)4-589C>T and IL10-1082G>A, might be associated with the occurrence, clinical course and functional outcome of an acute IS. Methods: We genotyped 290 subjects (145 consecutive IS cases and 145 age- and sex-matched controls) using a real-time PCR technology, prototypically designed for these mutations. Patients were evaluated with the Scandinavian Stroke Scale, and definitions of severity grouping and stroke progression were applied based on international agreements. Follow-up on months 1, 3, and 6 included registration of disease relapses, deaths and functional outcome measured by the Barthel Index. Results: IL4-589 and IL10-1082 genotypes did not significantly differ between cases and controls. The presence of IL4-589 T allele was associated with total IS recurrences [OR (95% CI) = 3.34 (1.18–9.45)], adjusted for age, sex and conventional risk factors. IL10-1082 GG genotype was found to significantly predict early stroke progression [OR (95% CI) = 3.72 (1.28–10.76)] and functional outcome by months 1 and 3 [OR (95% CI) = 5.03 (1.15–21.94) and 5.84 (1.07–31.85), respectively], after further corrections for stroke severity and TOAST categories. Conclusions: The functional IL4-589C>T and IL10-1082G>A polymorphisms seem not to be associated with occurrence of an IS, but may predict IS relapses, progressing strokes and functional outcome, independently of conventional risk factors. Our results merit further confirmation in future studies.

A 40-year-old HIV-negative Greek woman was admitted to the Department of Neurology at the University Medical Center of Patras with a 4-day history of progressive muscle weakness in her legs, accompanied by fever (39.5°C), diarrhea and urine retention and a 6-year history of oral and genital lesions that had relapsed 20 days prior to admission. Physical examination revealed multiple large aphthous lesions in the oral mucosa, extensive and deep anogenital ulcers, pseudofolliculitis and pathergy signs but no evidence of arthritis. Initial neurological examination showed muscle power grade 3/5 [Medical Research Council (MRC) scale] in the proximal and grade 4/5 in the distal muscles], brisk symmetrical tendon reflexes, extensor plantar response bilaterally, severe suppression of vibration sense below the knees (particularly on the right extremity) and bilateral reduction of pain appreciation below the T5 level. Neurological disability score in the expanded disability status scale (EDSS) was 6.5, indicating that bilateral assistance was required to walk 20 m. Cranial nerves and motor and sensory function of upper limbs were normal. Magnetic resonance imaging (MRI) of thoracic spinal cord revealed a long intramedullar lesion extending from C7 to T7 vertebrae with gadolinium-enhancement at T3–T4 level, whereas that of the brain showed three unenhanced small lesions at the brainstem (Figure 1.). Cerebrospinal fluid analysis revealed 60 lymphocytes/ml, normal protein and glucose content and negative oligoclonal bands. Figure 1. Magnetic resonance scan of the thoracic cord (sagittal T1-weighted images with gadolinium) showing the intramedullary enhanced lesion before (left image) and 1 month after treatment (right image). Ophthalmologic investigation disclosed posterior uveitis and spotty hemorrhagic foci on both eyes, whereas colonoscopy showed multiple deep ulcers along the large bowel. Erythrocyte sedimentation rate was 70 mm/h, HLA B51 was positive, whereas serum protein electrophoresis revealed a decrease …

The present study investigated differences and associations between cortical perfusion, nigrostriatal dopamine pathway and neuropsychological functions in different stages of Parkinson’s disease (PD). We recruited 53 non-demented PD patients divided into four groups according to the Hoehn and Yahr (HY) staging system and 20 healthy controls who were used in the comparison of the neuropsychological findings. Each patient underwent two separate brain single photon emission computed tomography (SPECT) studies (perfusion and dopamine transporter binding) as well as neuropsychological evaluation. Perfusion images of each patient were quantified and compared with a normative database provided by the NeuroGam software manufacturers. Mean values obtained from the cortical areas and neuropsychological measures in the different groups were also compared by analysis of covariance (ANCOVA) controlling for disease duration and educational level. We found cognitive deficits especially in the late PD stages (HY 3, 4 and 5) compared to the early stages (HY 1 and 2) and associations between cognitive decrements and cortical perfusion deterioration mainly in the frontal and posterior cortical areas. Compared with controls, PD patients showed impairments of cognition and cerebral perfusion that increased with clinical severity. Furthermore, we found a significant correlation between the performance on the phonemic fluency task and regional cerebral blood flow (rCBF) in the left frontal lobe. Dopamine transporter binding in the left caudate nucleus significantly correlated with blood flow in the left dorsolateral prefrontal cortex (DLPFC), but not with measures of executive functions. There are significant cognitive and perfusion deficits associated with PD progression, implying a multifactorial neurodegeneration process apart from dopamine depletion in the substantia nigra pars compacta (SNc).

Multiple sclerosis is the most common non-traumatic neurodegenerative disease in adults. Most of the patients present with both physical and mental deficits which reflect the dissemination of the lesions in the central nervous system, produced by the inflammatory process. The incomplete recovery after relapses, the accumulation of new deficits and the progressive nature of the condition interfere with daily activities of individuals and have a negative impact on their well-being. Indeed, studies show that quality of life measurements are constantly lower in patients with multiple sclerosis. Estimation of health-related quality of life is being increasingly recognized as necessary when analysing the effectiveness of treatment modalities and for the follow up of patients with chronic diseases such as multiple sclerosis. Current immunomodulatory interventions that are shown to reduce the frequency of relapses and delay disease progression might also have a positive effect on quality of life measurements. Additive pharmacological agents that target cognitive impairments and common symptoms such as depression, fatigue and pain, along with life-style modifications and rehabilitation programmes are also important for the appropriate management that aims to improve quality of life.

Research has recently focused on cognitive dysfunction in multiple sclerosis (MS). Cognitive deficits are frequently encountered in patients and account for important impairment in quality of life, therefore posing a major therapeutic challenge for the disease. We presently review studies on cognitive effects of pharmacological treatments in MS. There is evidence for a possible beneficial effect of immunomodulatory treatments, particularly of interferons, and also of acetylcholinesterase inhibitors on cognition in MS, which, however, requires evaluation in larger, multi-centre, longitudinal studies. Methodological issues and future prospects regarding the investigation of this issue are also discussed.

Although once considered rare, several more recent investigations have been published describing psychotic features in multiple sclerosis (MS). The association between the two conditions, however, remains unclear. Large-scale hospital-based, epidemiological and case studies have suggested a relationship between psychosis and MS through demonstrating their higher than chance co-occurrence, their temporal relationship, and their association with particular structural abnormalities in the brain (i.e., periventricular white matter and temporal demyelination). The etiology of psychosis in MS has also not been explained adequately. Regional demyelination and the use of corticosteroids have been implicated, yet their mechanisms of action have not been elucidated. The present review addresses what is known at this point in time regarding the occurrence of psychosis in the context of MS, the data regarding possible etiological factors, and the implications of these data and suggestions regarding diagnosis and treatment. Future research should explore the underlying pathophysiology of psychosis and multiple sclerosis to further our understanding of the central nervous system disease process. This research could help determine the features which would guide clinicians in identifying patients at risk of developing psychosis in the context of MS, as well as propose the optimal pharmacological intervention.

In the present study, we examined relationships between neuropsychological functions and brain single photon emission computed tomography (SPECT) regional cerebral blood flow (rCBF) observed at presurgical evaluation for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson’s disease (PD) patients. Twenty advanced non-demented PD patients, candidates for DBS surgery, underwent perfusion brain SPECT study and neuropsychological assessment prior to surgery (range: 30–50 days). Patients were further assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr (H&Y) scale. During all assessments patients were “on” standard medication. NeuroGam software, which permits voxel by voxel analysis, was used to compare the brain perfusion of PD patients with a normal database adjusted for sex and age. Neuropsychological scores were compared to age, education and sex-adjusted normative databases. Our results indicated that the distribution of rCBF showed significant differences when compared to an age- and sex-adjusted normative database. We found impaired blood flow in 17 (85%) of our patients in the left prefrontal lobe, in 14 (70%) in the right prefrontal lobe and in 11 (55%) in the left frontal and right parietal lobes. Neuropsychological testing revealed that 18 (90%) of our patients had significant impairments in measures of executive functions (set-shifting) and 15 (75%) in response inhibition. Furthermore, we found significant correlations between measures of visual attention, executive functions and the right frontal lobe region. The presence of widespread blood flow reduction was observed mainly in the frontal lobes of dementia-free patients with advanced PD. Furthermore, performance on specific cognitive measures was highly related to perfusion brain SPECT findings.

Derangement of cellular immunity is central in the pathophysiology of multiple sclerosis (MS) and is often manifested by abnormal cytokine production. We investigated cytokine secretion in peripheral blood mononuclear cells (PBMC) of 18 MS patients and 15 controls and correlated cytokine polarization with the nature of antigenic stimulus. We synthesized two novel citrullinated peptides, linear [Cit(91), Ala(96), Cit(97)]MBP(87-99) and cyclo(87-99)[Cit(91), Ala(96), Cit(97)]MBP(87-99) that resulted from citrullination of 91,97 Arg residues in antagonists, linear [Arg(91), Ala(96)]MBP(87-99) and cyclo(87-99)[Arg(91), Ala(96)]MBP(87-99) peptides. PBMC from MS patients and controls were cultured with citrullinated peptides, and both peptides caused a Th1 polarization in all MS patients studied. In contrast, culture with noncitrullinated MBP peptides resulted in heterogeneous cytokine secretion that differed between individual patients. Thus, citrullination of self-antigens may potentially trigger disease in susceptible individuals. This finding may open new avenues in drug design of new substances that inhibit citrullination and arrest epitope spreading and worsening of MS.