Altered intra- and interregional synchronization in the absence of the corpus callosum: a resting-state fMRI study

Agenesis of the corpus callosum (AgCC) can result in subtle to severe cognitive deficits. Individuals with impaired cognition often show abnormalities on resting-state functional magnetic resonance imaging (rs-fMRI). This study used rs-fMRI to investigate changes in regional homogeneity (ReHo) and functional connectivity (FC) among individuals with AgCC. AgCC individuals (n = 10) and age-, sex-, and education-matched healthy control subjects (n = 19) were included in this study. The ReHo values were calculated to represent spontaneous brain activity. The regions which showed altered ReHo were selected as seeds to compare FC with the whole brain between the AgCC group and the healthy control group. Compared with healthy control subjects, the AgCC individuals had increased ReHo in the left anterior cingulate gyrus, left rolandic operculum, and right precuneus and decreased ReHo in the right calcarine, right cingual gyrus and right cuneus gyrus. The right calcarine and the right lingual gyrus in the AgCC exhibited decreased FC with bilateral cuneus, superior occipital gyrus, Rolandic operculum, superior temporal gyrus, posterior central gyrus, and midcingulate gyrus.The right cuneus gyrus in the AgCC individuals exhibited decreased FC with the bilateral calcarine gyrus, left cuneus, and left superior occipital gyrus. Our study revealed several subareas within the visual cortex exhibited remarkable abnormalities of spontaneous brain activity and decreased FC with the higher-order cognitive cortex.The abnormalities of ReHo and FC in AgCC individuals may provide new insights into the neurological pathophysiology.     

Exposure to childhood trauma is associated with altered n-back activation and performance in healthy adults: implications for a commonly used working memory task

Previous research suggests that a history of early life stress (ELS) impacts working memory (WM) in adulthood. Despite the widespread use of WM paradigms, few studies have evaluated whether ELS exposure, in the absence of psychiatric illness, also impacts WM-associated brain activity in ways that might improve sensitivity to these ELS effects or provide insights into the mechanisms of these effects. This study evaluated whether ELS affects WM behavioral performance and task-associated activity by acquiring 3T functional images from 27 medication-free healthy adults (14 with ELS) during an N-back WM task that included 0- and 2-back components. Whole brain voxel-wise analysis was performed to evaluate WM activation, followed by region of interest analyses to evaluate relationships between activation and clinical variables. ELS was associated with poorer accuracy during the 2-back (79 %?±?19 vs. 92 %?±?9, p?=?0.049); accuracy and response time otherwise did not differ between groups. During the 0-back, ELS participants demonstrated increased activation in the superior temporal gyrus/insula, left inferior parietal lobule (IPL) (both corrected p?<?0.001), and middle temporal and parahippocampal gyrus (MTG/PHG)(corrected p?<?0.010). During the 2-back, ELS was associated with greater activation in the IPL, MTG/PHG and inferior frontal gyrus (corrected p?<?0.001), with a trend towards precuneus activation (p?=?0.080). These findings support previous research showing that ELS is associated with impaired neurobehavioral performance and changes in brain activation, suggesting recruitment of additional cognitive resources during WM in ELS. Based on these findings, ELS screening in future WM imaging studies appears warranted.     

Post-traumatic stress influences local and remote functional connectivity: a resting-state functional magnetic resonance imaging study

Post-traumatic stress disorder (PTSD) is associated with alterations in regional brain activation and remote functional connectivity (FC) in limbic and prefrontal cortex. However, little is known about local FC changes following a traumatic event. Resting-state functional magnetic resonance images were collected for typhoon survivors with (n = 27) and without PTSD (n = 33), and healthy controls (n = 30). Local FC was examined by calculating regional homogeneity (ReHo), and remote FC was investigated between regions showing significant ReHo group differences. The PTSD group showed ReHo changes in multiple regions, including the amygdala, parahippocampal gyrus, and prefrontal cortex relative to both control groups. Compared with healthy controls, typhoon survivors had increased ReHo in the insula/inferior frontal gyrus, middle and dorsal anterior cingulate cortex (MCC/dACC), as well as enhanced negative FC between the MCC/dACC and posterior cingulate cortex (PCC)/precuneus. The typhoon-exposed control group exhibited higher ReHo in the PCC/precuneus than the PTSD and healthy control groups. Furthermore, positive correlations were found between PTSD symptom severity and ReHo in several regions. Post-traumatic stress can influence local and remote FC, irrespective of PTSD diagnosis. Future studies are needed to validate the findings and to determine whether the alterations represent pre-existing or acquired deficits.     

Cognitive rehabilitation correlates with the functional connectivity of the anterior cingulate cortex in patients with multiple sclerosis

We investigated how resting state (RS) functional connectivity (FC) of the anterior cingulate cortex (ACC) correlates with cognitive rehabilitation in relapsing remitting multiple sclerosis (RRMS) patients. A neuropsychological assessment and RS fMRI at baseline and after 12 weeks were obtained from 20 RRMS patients, who were assigned randomly to undergo treatment (n?=?10) (treatment group-TG), which entailed computer-assisted cognitive rehabilitation of attention/information processing and executive functions for 3 days/week, or not to receive any cognitive rehabilitation (n?=?10) (control group-CG). Voxel-wise changes of ACC RS FC were assessed using SPM8. In both groups, at the two study time points, ACC activity was correlated with the bilateral middle and inferior frontal gyrus, basal ganglia, posterior cingulate cortex, cerebellum, precuneus, middle temporal gyrus, and inferior parietal lobule (IPL). At follow up, compared to baseline, the TG showed an increased FC of the ACC with the right middle frontal gyrus (MFG) and right IPL, while the CG showed a decreased FC of the ACC with the right cerebellum and right inferior temporal gyrus (ITG). A significant “treatment × time” interaction was found for the increased FC of the right IPL and for the decreased FC of the right ITG. In the TG only, significant correlations (p?PASAT performance and RS FC of the ACC with the right MFG (r?=?0.88) and right IPL (r?=?0.76). In MS, cognitive rehabilitation correlates with changes in RS FC of brain regions subserving the trained functions. fMRI might be useful to monitor rehabilitative strategies in MS.     

Natalizumab reduces serum pro-angiogenic activity in MS patients

Angiogenesis has been implicated in the pathobiology of multiple sclerosis (MS). Osteopontin exerts a pro-angiogenetic effect and is increased in body fluid of MS patients. To evaluate the effect of 1 year natalizumab treatment on serum pro-angiogenic activity and on plasma osteopontin levels in relapsing (RR) MS patients. Ten RRMS patients scheduled for natalizumab treatment were enrolled and evaluated at baseline and after 1-year natalizumab treatment. Pro-angiogenic activity was assessed by a chick embryo chorioallantoic membrane assay (CAM), osteopontin levels were evaluated by an enzyme-linked immunosorbent assay. Plasma and serum samples of 10 treatment-naïve RRMS and 10 healthy controls (HCs) were used as controls of baseline evaluations. Both treatment-naïve and natalizumab scheduled RRMS patients had higher baseline vessel density (22.0?±?3.9 and 22.5?±?2.6, p?<?0.0001) and higher osteopontin levels (65.7?±?24.3 ng/ml and 65.9?±?16.6 ng/ml, p?=?0.019 and p?=?0.029, respectively) than HCs (9.0?±?2.2; 48.5?±?7.8 ng/ml, respectively). Baseline osteopontin levels and vessel density were significantly correlated (rs?=?0.373, p?=?0.043). After 1 year of treatment, the number of vessels and the osteopontin levels, were significantly reduced (11.9?±?2.1, p?<?0.005; 49.3?±?20.0 ng/ml, p?=?0.028). Our results suggest that natalizumab could exert its anti-inflammatory properties also by inhibiting the angiogenetic mechanisms in RRMS patients.     

The Validation Study of Neurofilament Heavy Chain and 8-hydroxy-2′-deoxyguanosine as Plasma Biomarkers of Clinical/Paraclinical Activity in First and Relapsing-Remitting Demyelination Acute Attacks

Although current evidence mainly suggests immunopathogenesis of demyelination and neurodegeneration in multiple sclerosis (MS), there are results which document the importance of other factors, such as oxidative stress and its mediated injuries. The oxidative stress intensity in axonal damage during acute demyelination is little known. We performed this study as a cross-sectional biomarker validation study in order to evaluate the parameters of axonal damage (phosphorylated neurofilaments heavy chain (pNF-H)) and oxidative stress (8-hydroxy-2′-deoxyguanosine (8-OHdG)) in plasma of patients with initial and relapsing-remitting demyelination attacks, defined as clinically isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RRMS); and the correlations between these parameters and biological (index of blood brain barrier (BBB) permeability), clinical (index of disease progression), and radiological (T₁-Gd-enhancing lesion volume) activities of disease. Both parameters were increased in CIS and RRMS compared to control subjects (p < 0.05). The positive correlations were observed between 8-OHdG values and index of BBB permeability, clinical severity of disease, and demyelinated brain lesion volume, in CIS group (r > 0.50; p < 0.05). Similar correlations were obtained between pNF-H values and the above parameters, as well as the index of disease progression, in RRMS group (r > 0.30; p < 0.05). There was a significant correlation between values of 8-OHdG and pNF-H only in CIS group, r = 0.52, p < 0.05. While the plasma values of 8-OHdG reflect the degree of acute demyelination in CIS, pNF-H values reflect that in RRMS. The obtained results must be reevaluated in similar prospective studies related to their prognostic values.     

Assessment of Protein Prenylation Pathway in Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic inflammatory disorder with several genetic and environmental factors being implicated in its pathogenesis. Protein prenylation as one of the important posttranslational modifications of proteins has crucial role in immune system regulation. In the current case–control study, we compared expression of five genes coding for the different subunits of proteins implicated in protein prenylation in 50 Iranian MS patients with those of healthy subjects. No significant difference has been found in FNTA and PGGT1B expressions between cases and controls. Spearman correlation analysis between FNTA relative expression and disease duration showed significant correlation in male patients (r?=???0.671, P?=?0.024) but not female patients (r?=?0.253, P?=?0.12). FNTB expression was significantly higher in MS patients compared with healthy subjects. Spearman correlation analysis between FNTB relative expression and disease duration showed significant correlation in male patients (r?=??0.876, P?=?0.004) but not female patients (r?=?0.296, P?=?0.06). RABGGTA was significantly upregulated in total MS patients, total male patients, female patients aged between 30 and 40 and male patients aged >40 compared with corresponding control groups. RABGGTB was significantly downregulated in total MS patients, total female patients, and female patients aged >?40 compared with corresponding control groups. Totally, we demonstrated dysregulation of protein prenylation pathway in MS patients compared with healthy subjects. Future studies are needed to find the clinical implication of this pathway in MS patients.     

Expression Analysis of Long Non-coding RNAs in the Blood of Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system (CNS) with multiple genetic and environmental risk factors. Long non-coding RNAs (lncRNAs) have been recently reported to participate in the regulation of immune responses. Consequently, aberrant expression of lncRNAs has been suggested as an underlying cause of MS. In the present study, we evaluated the expression of three lncRNAs with putative roles in the regulation of immune response, namely TNF-α and heterogeneous nuclear ribonucleoprotein L (THRIL), Fas cell surface death receptor- antisense 1 (FAS-AS1), and plasmacytoma variant translocation 1 (PVT1) in circulating blood cells of 50 Iranian relapsing–remitting multiple sclerosis (RRMS) patients compared with healthy subjects by means of quantitative real-time polymerase chain reaction (PCR). We detected a significant downregulation of PVT1 and FAS-AS1 expressions in RRMS patients while a significant upregulation of THRIL in patients compared with controls (P < 0.001). Correlation analyses between lncRNA expression levels and clinical data of MS patients revealed no significant correlation between lncRNAs expression levels and Expanded Disability Status Scale (EDSS), a moderate correlation between PVT1 expression levels and duration of the disorder and no significant correlation between lncRNAs expression levels and age at onset. In addition, we demonstrated correlations between the expression levels of PVT1 and THRIL as well as expression levels of THRIL and FAS-AS1 in RRMS patients. In brief, we have demonstrated dysregulation of three lncRNAs in MS patients. Further studies are needed to explore the exact mechanisms by which these lncRNAs participate in regulation of immune responses.     

Lower functional connectivity of default mode network in cognitively normal young adults with mutation of <Emphasis Type="Italic">APP</Emphasis>, <Emphasis Type="Italic">presenilins</Emphasis> and <Emphasis Type="Italic">APOE ε4</Emphasis>

In this study, we used resting-state functional magnetic resonance imaging to explore the genetic effects of amyloid precursor protein (APP) or presenilins mutation and apolipoprotein E (APOE) ε4 on the default-mode network (DMN) in cognitively intact young adults (24.1 ± 2.5 years). Both the APP or presenilin-1/2 group and the APOE ε4 group had significantly lower DMN functional connectivity (FC) in the some brain regions like precuneus/middle cingulate cortices (PCu/MCC) than controls (AlphaSim corrected, P < 0.05). Only a lower FC tendency was demonstrated (control < APOE ε4 < APP or presenilin-1/2 group). Moreover, lower FC in PCu/MCC is correlated with some neuropsychological assessments such as similarity test in APOE ε4 group. These findings indicate that DMN FC alteration in APP or presenilin-1/2 or APOE ε4 subjects is prior to the occurrence of neurological alterations and clinical symptoms, and DMN FC might be a valuable biomarker to detect genetic risk in the preclinical stage.     

Relevance of early cervical cord volume loss in the disease evolution of clinically isolated syndrome and early multiple sclerosis: a 2-year follow-up study

Upper cervical cord area (UCCA) atrophy is a prognostic marker for clinical progression in longstanding multiple sclerosis (MS). The objectives of the study were to quantify UCCA atrophy and evaluate its impact in clinically isolated syndrome (CIS) and relapsing–remitting MS (RRMS); to compare converting CIS patients with stable CIS, and to study changes of UCCA and brain white matter (WM) and grey matter (GM) at 2-year follow-up. 110 therapy-naive patients including 53 CIS [6 ± 6 months after symptom onset (SO)] and 57 early RRMS (SO: 12 ± 9 months) underwent sagittal 3D-T1w brain MR (3T). Mean UCCA (C1–C3 level), WM and GM, disability status (EDSS), pyramidal and sensory functional scores, motoric fatigue were assessed at baseline (BL), 12 and 24 months. Volumes were compared with 34 age- and gender-matched healthy controls to assess atrophy. RRMS (78.1 ± 8.7 mm², p = 0.011) and converting CIS (77.3 ± 8.0 mm², p = 0.046) presented with baseline UCCA atrophy, when compared with controls (82.7 ± 5.2 mm²), but not stable CIS (82.6 ± 7.4 mm², p = 0.998). Baseline WM was reduced in RRMS (509.3 ± 25.7 ml vs. controls: 528.4 ± 24.1 ml, p = 0.032). Baseline UCCA correlated negative with muscular weakness and fatigability in all patients and RRMS. EDSS exceeding 3 was associated with lower baseline UCCA. Longitudinal atrophy rates were higher in UCCA than in brain volumes. Early cervical cord atrophy in CIS and RRMS was confirmed and may represent a potential new risk marker for conversion from CIS to MS. Baseline atrophy and atrophy change rates were higher in UCCA compared to WM and GM, suggesting that cervical cord volumetry might become an additional MRI marker relevant in future clinical studies in CIS and early MS.     

Insular multiple sclerosis lesions are associated with erectile dysfunction

Erectile function (EF) is frequently compromised in men with multiple sclerosis (MS). Functional neuroimaging in healthy men identified a network of brain areas, such as the insula, visual and somatosensory association areas, cingulate gyrus, prefrontal cortex, as well as subcortical regions, contributing to EF. This study intended to determine associations between EF deterioration during MS and cerebral MS-associated lesion sites. In 31 men with MS (mean age 38.2 ± 11.2 years), we evaluated MS-related EF deterioration by comparing scores of the 5-item International Index of Erectile Function-5 questionnaire (IIEF5) at the time of study and retrospectively, 3 months prior to MS diagnosis, by calculating score differences as DeltaIIEF5 (DeltaIIEF5 score < 0 indicated EF deterioration). To assess the impact of confounding factors of EF, patient age, disease duration, disease severity, depressiveness, bladder and bowel symptoms, and total cerebral MS lesion volume were correlated with DeltaIIEF5 scores (Spearman rank correlation) and compared between patients with and without EF deterioration (t tests or Mann–Whitney U test). MS lesions were assessed on T2-weighted magnetic resonance imaging (MRI; 1.5 or 3 T). We determined the lesion overlap (prevalence of identical lesion sites among patients), subtracted lesion overlaps in patients without EF deterioration from overlaps in patients with EF deterioration, and compared DeltaIIEF5 scores voxel-wise between patients with and without lesions in a given voxel (t test; significance: p < 0.05). In 14 patients (45.2%), DeltaIIEF5 scores indicated EF deterioration. DeltaIIEF5 scores were not associated with age (ρ = 0.06; p = 0.74), disease duration (ρ = 0.26; p = 0.15), disease severity (ρ = ? 0.19; p = 0.31), depressiveness (ρ = 0.07; p = 0.72), bladder symptoms (ρ = ? 0.11; p = 0.57), bowel symptoms (ρ = 0.17; p = 0.37), and total lesion volume (ρ = ? 0.13; p = 0.47). The voxel-wise analysis showed associations between EF deterioration and MS lesions primarily in the bilateral, and predominantly left juxtacortical insular region. In conclusion, MS lesions particularly in the left insular region, which is activated with sexual arousal, contribute to erectile dysfunction.     

The role of nonverbal working memory in morphosyntactic processing by children with specific language impairment and autism spectrum disorders

Background

Both children with autism spectrum disorders (ASD) and children with specific language impairment (SLI) have been shown to have difficulties with grammatical processing. A comparison of these two populations with neurodevelopmental disorders was undertaken to examine similarities and differences in the mechanisms that may underlie grammatical processing. Research has shown that working memory (WM) is recruited during grammatical processing. The goal of this study was to examine morphosyntactic processing on a grammatical judgment task in children who varied in clinical diagnosis and language abilities and to assess the extent to which performance is predicted by nonverbal working memory (WM). Two theoretical perspectives were evaluated relative to performance on the grammatical judgment task—the “working memory” account and the “wrap-up” account. These accounts make contrasting predictions about the detection of grammatical errors occurring early versus late in the sentence.

Methods

Participants were 84 school-age children with SLI (n?=?21), ASD (n?=?27), and typical development (TD, n?=?36). Performance was analyzed based on diagnostic group as well as language status (normal language, NL, n?=?54, and language impairment, LI, n?=?30). A grammatical judgment task was used in which the position of the error in the sentence (early versus late) was manipulated. A visual WM task (N-back) was administered and the ability of WM to predict morphosyntactic processing was assessed.

Results

Groups differed significantly in their sensitivity to grammatical errors (TD?>?SLI and NL?>?LI) but did not differ in nonverbal WM. Overall, children in all groups were more sensitive and quicker at detecting errors occurring late in the sentence than early in the sentence. Nonverbal WM predicted morphosyntactic processing across groups, but the specific profile of association between WM and early versus late error detection was reversed for children with and without language impairment.

Conclusions

Findings primarily support a “wrap up” account whereby the accumulating sentence context for errors positioned late in the sentence (rather than early) appeared to facilitate morphosyntactic processing. Although none of the groups displayed deficits in visual WM, individual differences in these nonverbal WM resources predicted proficiency in morphosyntactic processing.

     

Correlation of occupational stress with depression,anxiety, and sleep in Korean dentists: cross-sectional study

Background

This study aimed to investigate the degree of occupational stress and the clinical mental state of dentists. In addition, we investigated the correlation of occupational stress with depression, anxiety, and sleep among dentists in Korea.

Methods

A cross-sectional survey on 231 dentists was conducted using the Doctor Job Stress Scale, Center for Epidemiologic Studies Depression Scale (CES-D), State-Trait Anxiety Index (STAI), and Pittsburgh Sleep Quality Index (PSQI). Correlation of occupational stress with mental health was investigated by adjusted multiple regression analysis.

Results

The scores of CES-D, STAI, and PSQI revealed a significant correlation with the Doctor Job Stress Scale (t?=?3.93, P?<?0.0001; t?=?4.05, P?<?0.0001; t?=?4.18, P?<?0.0001, respectively). In particular, patient factors and clinical responsibility/judgment factors were significantly associated with depression (t?=?2.80, P?=?0.0056; t?=?4.93, P?<?0.0001, respectively), anxiety (t?=?2.35, P?=?0.0195; t?=?5.11, P?<?0.0001, respectively), and sleep (t?=?3.78, P?=?0.0002; t?=?4.30, P?<?0.0001, respectively), whereas work factors were not associated with any mental health state.

Conclusions

This study confirms that dentists as professions experience more severe mental states. For successful mental health care among dentists, stress management focusing on interpersonal relationship with patients and responsibility as an expert rather than the intensity of work should be considered.

     

Short video interventions to reduce mental health stigma: a multi-centre randomised controlled trial in nursing high schools

Background

We aimed to assess whether short video interventions could reduce stigma among nursing students.

Methods

A multi-centre, randomised controlled trial was conducted. Participating schools were randomly selected and randomly assigned to receive: (1) an informational leaflet, (2) a short video intervention or (3) a seminar involving direct contact with a service user. The Community Attitudes towards Mental Illness (CAMI) and Reported and Intended Behaviour Scale (RIBS) were selected as primary outcome measures. SPANOVA models were built and Cohen’s d calculated to assess the overall effects in each of the trial arms.

Results

Compared to the baseline, effect sizes immediately after the intervention were small in the flyer arm (CAMI: d?=?0.25; RIBS: d?=?0.07), medium in the seminar arm (CAMI: d?=?0.61; RIBS: d?=?0.58), and medium in the video arm (CAMI: d?=?0.49 RIBS: d?=?0.26; n?=?237). Effect sizes at the follow-up were vanishing in the flyer arm (CAMI: d?=?0.05; RIBS: d?=?0.04), medium in the seminar arm (CAMI: d?=?0.43; RIBS: d?=?0.26; n?=?254), and small in the video arm (CAMI: d?=?0.22 RIBS: d?=?0.21; n?=?237).

Conclusion

Seminar had the strongest and relatively stable effect on students’ attitudes and intended behaviour, but the effect of short video interventions was also considerable and stable over time. Since short effective video interventions are relatively cheap, conveniently accessible and easy to disseminate globally, we recommend them for further research and development.

     

Primary lateral sclerosis and the amyotrophic lateral sclerosis–frontotemporal dementia spectrum

Aim

To investigate whether primary lateral sclerosis (PLS) represents part of the amyotrophic lateral sclerosis–frontotemporal dementia (ALS–FTD) spectrum of diseases.

Methods

Comprehensive assessment was taken on 21 patients with PLS and results were compared to patients diagnosed with pure motor ALS (n?=?27) and ALS–FTD (n?=?12). Clinical features, Addenbrooke’s Cognitive Examination (ACE) scores, Motor Neuron Disease Behaviour (Mind-B) scores, motor disability on the ALS functional rating scale (ALSFRS) and survival times were documented. Motor cortex excitability was evaluated using transcranial magnetic stimulation (TMS).

Results

Global cognition was impaired in PLS (mean total ACE score 82.5?±?13.6), similar to ALS–FTD (mean total ACE score 76.3?±?7.7, p?>?0.05) while behavioural impairments were not prominent. TMS revealed that resting motor threshold (RMT) was significantly higher in PLS (75.5?±?6.2) compared ALS–FTD (50.1?±?7.2, p?<?0.001) and ALS (62.3?±?12.6, p?=?0.046). Average short-interval intracortical inhibition (SICI) was similar in all three patient groups. The mean survival time was longest in PLS (217.4?±?22.4 months) and shortest in ALS–FTD (38.5?±?4.5 months, p?=?0.002). Bulbar onset disease (β?=???0.45, p?=?0.007) and RMT (β?=?0.54, p?=?0.001) were independent predictors of global cognition while motor scores (β?=?0.47, p?=?0.036) and SICI (β?=?0.58, p?=?0.006) were significantly associated with ALSFRS.

Conclusion

The cognitive profile in PLS resembles ALS–FTD, without prominent behavioural disturbances. A higher RMT in PLS than ALS and ALS–FTD is consistent with differential cortical motor neuronal abnormalities and more severe involvement of corticospinal axons while SICI, indicative of inhibitory interneuronal dysfunction was comparable with ALS and ALS–FTD. Overall, while these findings support the notion that PLS lies on the ALS–FTD spectrum, the mechanisms underlying slow disease progression are likely to be distinct in PLS.

     

Non-motor and Extracerebellar Features in Spinocerebellar Ataxia Type 2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant degenerative disease. Pathological studies have demonstrated not only cerebellar and brainstem atrophy, but substantia nigra, motoneurons, basal ganglia, thalamus, and peripheral nerves involvement. These findings may explain non-motor and extra-cerebellar features in SCA2. We accessed the non-motor symptoms and extra-cerebellar signs in SCA2 patients in order to provide a better understanding on pathophysiological mechanisms and natural history of brain degeneration in the disease. Thirty-three SCA2 patients were evaluated and compared with 26 healthy subjects. We investigated the following variables: sleep disorders, cognitive deficit, olfactory impairment, urinary dysfunction, psychiatric symptoms, cramps, pain, movement disorders, and weight loss. SCA2 had a high frequency of REM sleep behavior disorder (48.48 %, N?=?16) as well as excessive daytime sleepiness (42.42 %, N?=?14). Chorea was present in 15.15 % (N?=?5), dystonia in 27.27 % (N?=?9), and parkinsonism in 27.27 % (N?=?9). Slow saccadic pursuit was present in 87.87 % (N?=?29) and ophtalmoparesis in 78.78 % (N?=?26) of patients. Regarding sleep disorders, 18.18 % (N?=?6) of patients had restless leg syndrome. Dysphagia was present in 39.39 % (N?=?13), weight loss 24.24 % (N?=?8), and urinary dysfunction 27.27 % (N?=?9). Cramps was present in only 6 % of patients (N?=?2). This study highlighted the high frequency of non-motor symptoms and extra-cerebellar signs in SCA2. Our findings demonstrate the widespread of nervous system involvement in SCA2 patients and contribute to better understand the natural history of brain degeneration in this genetic condition.     

The Usefulness of the TOAST Classification and Prognostic Significance of Pyramidal Symptoms During the Acute Phase of Cerebellar Ischemic Stroke

Cerebellar stroke is a rare condition with very nonspecific clinical features. The symptoms in the acute phase could imitate acute peripheral vestibular disorders or a brainstem lesion. The aim of this study was to assess the usefulness of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification in cerebellar stroke and the impact of clinical features on the prognosis. We retrospectively analyzed 107 patients with diagnosed ischemic cerebellar infarction. We studied the clinical features and compared them based on the location of the ischemic lesion and its distribution in the posterior interior cerebellar artery (PICA), superior cerebellar artery (SCA), and anterior inferior cerebellar artery (AICA) territories. According to the TOAST classification, stroke was more prevalent in atrial fibrillation (26/107) and when the lesion was in the PICA territory (39/107). Pyramidal signs occurred in 29/107 of patients and were more prevalent when the lesion was distributed in more than two vascular regions (p?=?0.00640). Mortality was higher among patients with ischemic lesion caused by cardiac sources (p?=?0.00094) and with pyramidal signs (p?=?0.00640). The TOAST classification is less useful in assessing supratentorial ischemic infarcts. Cardioembolic etiology, location of the ischemic lesion, and pyramidal signs support a negative prognosis.     

‘Timed up and go’ and brain atrophy: a preliminary MRI study to assess functional mobility performance in multiple sclerosis

Motor and cognitive disabilities are related to brain atrophy in multiple sclerosis (MS). ‘Timed up and go’ (TUG) has been recently tested in MS as functional mobility test, as it is able to evaluate ambulation/coordination-related tasks, as well as cognitive function related to mobility. The objective of this study is to evaluate the relationship between brain volumes and TUG performances. Inclusion criteria were a diagnosis of MS and the ability to walk at least 20 m. TUG was performed using a wearable inertial sensor. Times and velocities of TUG sub-phases were calculated by processing trunk acceleration data. Patients underwent to a brain MRI, and volumes of whole brain, white matter (WM), grey matter (GM), and cortical GM (C) were estimated with SIENAX. Sixty patients were enrolled. Mean age was 41.5 ± 11.6 years and mean EDSS 2.3 ± 1.2. Total TUG duration was correlated to lower WM (ρ = 0.358, p = 0.005) and GM (ρ = 0.309, p = 0.017) volumes. A stronger association with lower GM volume was observed for intermediate (ρ = 0.427, p = 0.001) and final turning (ρ = 0.390, p = 0.002). TUG is a useful tool in a clinical setting as it can not only evaluate patients’ disability in terms of impaired functional mobility, but also estimate pathological features, such as grey atrophy.     

The association between retinal nerve fibre layer thickness and corpus callosum index in different clinical subtypes of multiple sclerosis

The objective of this paper is to evaluate the association between physical disability in multiple sclerosis (MS) patients, the thickness of the retinal nerve fibre layer (RNFL) and corpus callosum volumes, as expressed by the corpus callosum index (CCI). This study was based on a cohort of 212 MS patients and 52 healthy control subjects, who were age and gender matched. The MS patients included 144 women and 177 relapsing-remitting MS (RRMS) patients. Peripapillary and volumetric optical coherence tomography (OCT) scans of the macula were performed using spectral-domain OCT technology. All magnetic resonance imaging (MRI) scans were performed using 1.5-T systems. CCI and RNFL were lower in MS than healthy control subjects (0.341 versus 0.386, p < 0.01 and 92.1 versus 105.0, p < 0.01). In addition, CCI correlated with RNFL (r = 0.464, p < 0.01). This was also true for the subgroup of patients with no history of optic neuritis (ON). There is a correlation between the thickness of the RNFL and CCI values in MS patients with no history of ON, which suggests that OCT might be a suitable marker for neurodegeneration in MS clinical trials.