Pregnancy effect on disease activity in women with multiple sclerosis treated with cladribine.

INTRODUCTION: Cladribine is an oral immune reconstitution therapy for relapsing multiple sclerosis (RMS). Hormonal and immune changes are responsible for the decline of disease activity in the third trimester of pregnancy and disease reactivation in the early post-partum period.We investigate the impact of pregnancy on disease activity in women with MS who conceived after cladribine treatment. METHODS: We recruited women of childbearing age with relapsing-remitting MS (RRMS) who became pregnant or not after being treated with cladribine. For both groups, demographic, clinical and radiological data were collected 1 year before and after treatment during a mean follow-up of 3.53 years. We compared disease activity over time between groups using variance analysis for repeated measures. RESULTS: 48 childbearing women were included. 25 women had a pregnancy after a mean of 1.75 years from the first treatment cycle. Women with or without pregnancy did not differ in demographics or pre-cladribine disease activity. No significant differences in disease activity or EDSS worsening were found between women with or without pregnancy. DISCUSSION: Our findings suggest that pregnancy does not appear to influence disease activity and disability in women previously treated with cladribine; further studies with larger numbers and longer follow-up are needed to confirm this finding.

Sexual dysfunction in multiple sclerosis: The impact of different MSISQ-19 cut-offs on prevalence and associated risk factors.

BACKGROUND: Although multiple sclerosis (MS) Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a widely applied tool, no unique definition of sexual dysfunction (SD) based on its score exists. OBJECTIVE: To explore the impact of different MSISQ-19 cut-offs on SD prevalence and associated risk factors, providing relevant information for its application in research and clinical settings. METHODS: After defining SD according to two different MSISQ-19 cut-offs in 1155 people with MS (pwMS), we evaluated SD prevalence and association with sociodemographic and clinical features, mood status and disability via logistic regression. RESULTS: Depending on the chosen cut-off, 45% to 54% of pwMS reported SD. SD defined as MSISQ-19 score >30 was predicted by age (OR=1.01, p=0.047), cognition (OR=0.96, p=0.004) and anxiety (OR=1.03, p=0.019). SD defined as a score >3 on any MSISQ-19 item was predicted by motor disability (OR=1.12, p=0.003) and cognition (OR= 0.96, p=0.002). CONCLUSION: Applying different MSISQ-19 cut-offs influences both the estimated prevalence and the identification of risk factors for SD, a finding that should be considered during study planning and data interpretation. Preserved cognition exerts a protective effect towards SD regardless from the specific study setting, representing a key point for the implementation of preventive and therapeutic strategies.

Leveraging the Full Continuum of Care to Prevent Opioid Use Disorder.

Substance use disorder prevention programs are most effective when matched appropriately to the baseline risk of the population. Individuals who misuse opioids often have unique risk profiles different from those who use other substances such as alcohol or cannabis. However, most substance use prevention programs are geared toward universal audiences, neglecting key inflection points along the continuum of care. The HEAL Prevention Cooperative (HPC) is a unique cohort of research projects that represents a continuum of care, from community-level universal prevention to indicated prevention among older adolescents and young adults who are currently misusing opioids or other substances. This paper describes the theoretical basis for addressing opioid misuse and opioid use disorder across the prevention continuum, using examples from research projects in the HPC.

Functional brain connectomes reflect acute and chronic cannabis use.

Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on whole-brain network organization. The present study attempted to identify changes in the whole-brain human functional connectome as assessed with ultra-high field (7T) resting state scans of cannabis users (N = 26) during placebo and following vaporization of cannabis. Two distinct data-driven methodologies, i.e. network-based statistics (NBS) and connICA, were used to identify changes in functional connectomes associated with acute cannabis intoxication and history of cannabis use. Both methodologies revealed a broad state of hyperconnectivity within the entire range of major brain networks in chronic cannabis users compared to occasional cannabis users, which might be reflective of an adaptive network reorganization following prolonged cannabis exposure. The connICA methodology also extracted a distinct spatial connectivity pattern of hypoconnectivity involving the dorsal attention, limbic, subcortical and cerebellum networks and of hyperconnectivity between the default mode and ventral attention network, that was associated with the feeling of subjective high during THC intoxication. Whole-brain network approaches identified spatial patterns in functional brain connectomes that distinguished acute from chronic cannabis use, and offer an important utility for probing the interplay between short and long-term alterations in functional brain dynamics when progressing from occasional to chronic use of cannabis.

Treatment with K6PC-5, a selective stimulator of SPHK1, ameliorates intestinal homeostasis in an animal model of Huntington's disease.

Emerging evidence indicates that Huntington's disease (HD) may be described as multi-organ pathology. In this context, we and others have contributed to demonstrate that the disease is characterized by an impairment of the homeostasis of gastro-intestinal (GI) tract. Sphingolipids represent a class of molecules involved in the regulation and maintenance of different tissues and organs including GI system. In this study, we investigated whether the alteration of Sphingosine-1-phosphate (S1P) metabolism, previously described in human HD brains and animal models, is also detectable peripherally in R6/2 HD mice. Our findings indicate, for the first time, that sphingolipid metabolism is perturbed early in the disease in the intestinal tract of HD mice and, its modulation by K6PC-5, a selective activator of S1P synthesis, preserved intestinal integrity and homeostasis. These results further support the evidence that modulation of sphingolipid pathways may represent a potential therapeutic option in HD and suggest that it has also the potential to counteract the peripheral disturbances which may usually complicate the management of the disease and affect patient's quality of life.

Prevalence of dysphagia in a consecutive cohort of subjects with MS using fibre-optic endoscopy.

INTRODUCTION: Multiple sclerosis (MS) refers to chronic inflammation of the central nervous system including the brain and spinal cord. Dysphagia is a symptom that represents challenges in clinical practice. The aim of the present study was to evaluate the prevalence of dysphagia in an Italian cohort of subjects with MS using the Dysphagia Outcome Severity Score (DOSS), based on fibre-optic endoscopy, and determine factors that correlate with the presence of swallowing problems. MATHERIALS AND METHODS: Data were collected in a multicentre study from a consecutive sample of MS patients, irrespective of self-reported dysphagia. The study included 215 subjects. Possible scores for DOSS range from 7 to 1, with 7 indicating normal swallowing. RESULTS: One hundred twenty-four (57.7%) subjects demonstrated abnormal swallowing and 57 (26.5%) of these had swallowing problems that required nutrition/diet modifications when evaluated objectively with fibre-optic endoscopy. Subjects with dysphagia were more severely disabled and more often had a progressive form of MS, compared to MS subjects with normal swallowing. In subjects with EDSS, < 4, 8 (13.3%), had a DOSS < 4. Seventy-five percent of subjects older than 60 years of age had dysphagia. CONCLUSION: In this sample of MS patients, more nearly 60% showed swallowing problems.

Curcumin dietary supplementation ameliorates disease phenotype in an animal model of Huntington's disease.

Huntington's disease (HD) has traditionally been described as a disorder purely of the brain; however, evidence indicates that peripheral abnormalities are also commonly seen. Among others, severe unintended body weight loss represents a prevalent and often debilitating feature of HD pathology, with no therapies available. It correlates with disease progression and significantly affects the quality of life of HD patients. Curcumin, a naturally occurring polyphenol with multiple therapeutic properties, has been validated to exert important beneficial effects under health conditions as well as in different pathological settings, including neurodegenerative and gastrointestinal (GI) disorders. Here, we investigated the potential therapeutic action that curcumin-supplemented diet may exert on central and peripheral dysfunctions in R6/2 mice, a well-characterized HD animal model which recapitulates some features of human pathology. Maintenance of normal motor function, protection from neuropathology and from GI dysfunction and preservation of GI emptying and conserved intestinal contractility, proved the beneficial role of life-long dietary curcumin in HD and corroborated the potential of the compound to be exploited to alleviate very debilitating symptoms associated with the disease.

Comparison of genioglossus muscle activity and efficiency of dexmedetomidine or propofol during drug-induced sleep endoscopy in patients with obstructive sleep apnea/hypopnea syndrome.

OBJECTIVE: The purpose of this study is to evaluate the haemodynamic and respiratory effects of dexmedetomidine vs. propofol in patients with OSAHS during the drug-induced sleep endoscopy (DISE), and analyze simultaneously the electromyography of genioglossus muscle. PATIENTS AND METHODS: We conducted a study on 50 patients with OSAHS; patients were subjected to DISE with simultaneous polygraphic cardiorespiratory measurement and electromyography of genioglossus muscle. Patients undergoing DISE were divided in two groups: in Group A (19 M; 8 W) was administered propofol TCI and in Group B (16 M; 7 W) was administered dexmedetomidine TCI. RESULTS: In Group A, a mean minimal SpO2 decreasing of 3.7% (p=0.000) and a mean SpO2 decreasing of 1.6% (p 0.001) was noticed, while there was an increase in BP20 of 14.8% (p=0.000) and HR20 of 11.1% (p=0.000). In Group B, it was showed a decreasing of mean minimal SpO2 and mean SpO2 values, about 1.8% (p=0.000) and 1.1% (p 0.009) respectively, while there was an increase of BP20 and HR20, about 8.7% (p=0.000) and 8% (p 0.002), respectively. Despite EMG activity comparing spontaneous sleep with propofol-DISE, there is a statistically significative change for the amplitude (p=0.040) and an increase of 7.01% for the area under the curve (AUC). Comparing spontaneous sleep with dexmedetomidine-DISE induced one, there is only an increase of 25.87% in the AUC. CONCLUSIONS: A greater worsening of the cardio-respiratory basal values was noted after sleep induction with Propofol and same results were obtained confronting EMG of genioglossus muscle data.

Discontinuation of teriflunomide and dimethyl fumarate in a large Italian multicentre population: a 24-month real-world experience.

BACKGROUND: Teriflunomide (TRF) and Dimethyl fumarate (DMF) are licensed drugs for relapsing-remitting Multiple Sclerosis (RRMS). OBJECTIVES: We aimed to compare the rate and the time to discontinuation among persons with RRMS (pwRRMS), newly treated with TRF and DMF. MATERIALS AND METHODS: A retrospective study on prospectively collected data was performed in nine tertiary MS centers, in Italy. The 24-month discontinuation rate in the two cohorts was the primary study outcome. We also assessed the time to discontinuation and reasons of therapy withdrawn. Discontinuation of TRF and DMF was defined as a gap of treatment ≥ 60 days. RESULTS: A cohort of 903 pwRRMS (316 on TRF and 587 on DMF) was analyzed. During 24 months of follow-up, pwRRMS on TRF and DMF showed similar discontinuation rates. The analysis of predictors with Cox regression model showed differences between the two groups (p for log-rank test = 0.007); male gender [HR 2.21 (1.00-4.90); p = 0.01] and the number of previous switches [HR 1.47 (1.16-1.86); p = 0.01] were associated with higher hazard of discontinuation in the DMF group. CONCLUSIONS: In a real-world setting, pwRRMS on TRF and DMF had similar discontinuation rates over 24 months. Male pwRRMS on DMF with a previous history of therapeutic failure are at more risk of discontinuation therapy.

Late-onset and young-onset relapsing-remitting multiple sclerosis: evidence from a retrospective long-term follow-up study.

BACKGROUND AND PURPOSE: Late-onset multiple sclerosis (MS) has a prevalence of about 10-20% in natural history MS studies. Few data have been published about the long-term disease trajectory in the cohort of late-onset relapsing-remitting MS (LORRMS). The aim of this study was to identify the risk factors for reaching an Expanded Disability Status Scale (EDSS) score of 6.0 in LORRMS (onset at >40 years of age) and young-onset relapsing-remitting MS (YORRMS) (onset between 18 and 40 years of age). METHODS: Clinical and radiological [magnetic resonance imaging (MRI) of the brain] follow-up data were collected. Disability was assessed by EDSS score. A Cox proportional hazards model was used to evaluate the demographic and clinical predictors of reaching an EDSS score of 6.0 in the two cohorts. RESULTS: A total of 671 patients with relapsing-remitting MS were enrolled, 143 (21.3%) with LORRMS and 528 (78.7%) with YORRMS. In LORRMS, age at onset was 47.8 ± 5.3 (mean ± SD) years and duration of follow-up was 120.7 ± 52.7 months. In YORRMS, age at onset was 27 ± 2.7 years and duration of follow-up was 149.9 ± 92.7 months. The survival curve analyses showed a higher probability of reaching an EDSS score of 6.0 for LORRMS in a shorter time (months) than for YORRMS (94.2 vs. 103.2 months; log-rank 8.8; P < 0.05). On MRI, YORRMS showed more brain inflammatory features than LORRMS. In the multivariate Cox model, age at onset [Exp(B) value, 6.5; 95% confidence interval, 1.9-22.6; P < 0.001] and male gender [Exp(B) value, 1.7; 95% confidence interval, 1.0-2.8; P < 0.05] were the strongest predictors of reaching an EDSS score of 6.0. CONCLUSIONS: The male population with LORRMS reached severe disability faster than those with YORRMS, even when YORRMS showed more brain inflammatory features on MRI.

Lateral switch to IFN beta-1a 44 mcg may be effective as escalation switch to fingolimod in selected persons with relapsing remitting multiple sclerosis: a real-world setting experience.

BACKGROUND: The efficacy of lateral and escalation switch is a challenge in MS. We compared in a real-world setting the efficacy of switching to IFN beta-1a 44 mcg or to fingolimod in persons with relapsing remitting MS (pwRRMS) who failed with others injectable IFNs or glatiramer acetate. RESEARCH DESIGN AND METHODS: retrospective analysis of 24 months prospectively-collected data at the MS center of the University of Catania, Italy was performed. Patients who were switched to IFN-beta 1a 44 mcg or fingolimod were analyzed using propensity-score covariate adjustment model within demographic (e.g. age and gender) and disease (e.g. timing of pre-switch relapse) characteristics. Switching-time was considered the starting-time of the observation. RESULTS: 43 pwRRMS on IFN beta-1a 44 mcg and 49 pwRRMS on fingolimod were included. Baseline characteristics differed for EDSS score and number of T2 lesions (higher in group on fingolimod). At 24 months of follow up, both groups showed no differences in the survival curves of reaching a first new relapse, new T2 and Gd+ MRI brain lesions, even corrected for the propensity score covariate adjustment. CONCLUSIONS: lateral switch to IFN beta-1a 44 mcg and escalation switch to fingolimod showed same ability in influencing RRMS disease activity at 24 months.

Identifying neuropathic pain in patients with multiple sclerosis: a cross-sectional multicenter study using highly specific criteria.

BACKGROUND: Pain is a common and heterogeneous complication of multiple sclerosis (MS). In this multicenter, cross sectional study, we aimed at investigating the prevalence of pain in MS using highly specific criteria for distinguishing the different types of pain. MATERIALS AND METHODS: After a structured interview, in patients with pain, clinical examination and DN4 questionnaire were used for distinguishing neuropathic and nociceptive pain. In subjects with neuropathic pain, the Neuropathic Pain Symptom Inventory was used for differentiating neuropathic pain symptoms. RESULTS: We enrolled 1249 participants (832 F, 417 M, mean age 33.9 years, mean disease duration 8 years, mean EDSS 3.2); based on clinical evaluation and DN4 score 429 patients (34.34%) were classified with pain (470 pain syndromes): 286 nociceptive pain syndromes and 184 neuropathic pain syndromes. Multivariate analysis showed that pain was associated with age, gender and disease severity and that neuropathic pain was distinctly associated with EDSS. CONCLUSIONS: Our study, providing definite information on the prevalence, characteristics and variables associated with neuropathic pain due to MS, shows that a more severe disease course is associated with a higher risk of neuropathic pain. Our findings might, therefore, provide a basis for improving the clinical management of this common MS complication.

Neuromedin U potentiates ADP- and epinephrine-induced human platelet activation.

Neuromedin U (NmU) is a pleiotropic hypothalamic neuropeptide involved in the gut-brain axis. It acts via both a Gαq/11-coupled receptor (NMUR1) and a Gαi-coupled receptor (NMUR2) in different cell types. Expression of both receptors was reported in platelets, but their significance for NmU signaling remains elusive. We studied the potential effects of NmU on human platelet activation. In platelet-rich plasma (PRP), NmU alone (up to 10µM) did not induce any measurable aggregation, but at nanomolar concentrations, it potentiated platelet aggregation by low (mean 0.47µM) ADP concentrations (from 25.9±3.6% to 74.8±2.7% maximal aggregation for ADP vs. ADP+NmU, 100nM, mean±SEM, n=13), accompanied by platelet P-selectin expression and intracellular calcium mobilization. Accordingly, platelet preincubation with NmU for 2min sensitized platelets for subsequent activation by ADP. When P2Y1 was inactivated by 50µM MRS2179, NmU comparably potentiated ADP-induced PRP aggregation, suggestive of cooperative activation with Gαi-coupled P2Y12. Likewise, NmU potentiated platelet aggregation by Gαi-operated epinephrine at subthreshold concentrations (99ng/ml, mean), but not that by Gαq-dependent serotonin (20µM). Platelet aggregation by NmU/epinephrine combination was fully inhibited by the Gαq inhibitor YM-254890 (1µM). qPCR detection and western blot analysis substantiated platelet expression of NMUR1 in different donors, a finding collectively complying with functionally relevant Gαq/11-mediated activation of platelet NMUR1 by NmU. Our findings advocate further studies on platelet sensitization by NmU, released during vascular activation and injury, to define its role as a modifier of platelet responsiveness to the physiological activation signals, operational in cardiovascular health and disease.

The combined action of a passive exoskeleton and an EMG-controlled neuroprosthesis for upper limb stroke rehabilitation: First results of the RETRAINER project.

The combined use of Functional Electrical Stimulation (FES) and robotic technologies is advocated to improve rehabilitation outcomes after stroke. This work describes an arm rehabilitation system developed within the European project RETRAINER. The system consists of a passive 4-degrees-of-freedom exoskeleton equipped with springs to provide gravity compensation and electromagnetic brakes to hold target positions. FES is integrated in the system to provide additional support to the most impaired muscles. FES is triggered based on the volitional EMG signal of the same stimulated muscle; in order to encourage the active involvement of the patient the volitional EMG is also monitored throughout the task execution and based on it a happy or sad emoji is visualized at the end of each task. The control interface control of the system provides a GUI and multiple software tools to organize rehabilitation exercises and monitor rehabilitation progress. The functionality and the usability of the system was evaluated on four stroke patients. All patients were able to use the system and judged positively its wearability and the provided support. They were able to trigger the stimulation based on their residual muscle activity and provided different levels of active involvement in the exercise, in agreement with their level of impairment. A randomized controlled trial aimed at evaluating the effectiveness of the RETRAINER system to improve arm function after stroke is currently ongoing.

Episodic replacement of clotting factor concentrates does not prevent bleeding or musculoskeletal damage - the MUSFIH study.

PATIENTS AND METHODS: A longitudinal study was carried out in 255 children from 10 centres in nine developing countries over 5 years to assess the musculoskeletal outcome of children on episodic factor replacement. Outcome was documented by assessment of the annual joint bleeding rate (AJBR), WFH clinical and Pettersson radiological joint scores as well as the FISH score for activities. Of the 203 patients for whom data was available at the end of 5 years, 164 who had received only episodic treatment are included in this report. RESULTS: The median age at the beginning of the study was 10 years (IQR 7-12). The median clotting factor concentrate (CFC) usage was 662 IU kg-1 year-1 (IQ range: 280-1437). The median AJBR was 10 (IQ range: 5-17). The median AJBR was higher in the older children with the median being 5 for the 5 year old child, while it was 9 for the 10 year old and 11 for children older than 15. Given the episodic nature of the replacement therapy, those with a higher AJBR used significantly greater annual CFC doses (P < 0.001); The median change in WFH clinical score and Pettersson radiological score over the 5 years was 0.4/year for each, while the FISH deteriorated at a rate of 0.2/year with poor correlation of these changes with CFC dose. WFH and FISH scores were significantly worse in those with an AJBR of >3 per year (P = 0.001). The change in the Pettersson score was significantly more in those with an AJBR of >5 per year (P = 0.020). Significant changes in FISH scores were only noted after 10 years of age. CONCLUSION: Episodic CFC replacement over a large range of doses does not alter the natural course of bleeding in haemophilia or the musculoskeletal deterioration and should not be recommended as a long term option for treatment. Prophylaxis is the only way to preserve musculoskeletal function in haemophilia.

Ising model with conserved magnetization on the human connectome: Implications on the relation structure-function in wakefulness and anesthesia.

Dynamical models implemented on the large scale architecture of the human brain may shed light on how a function arises from the underlying structure. This is the case notably for simple abstract models, such as the Ising model. We compare the spin correlations of the Ising model and the empirical functional brain correlations, both at the single link level and at the modular level, and show that their match increases at the modular level in anesthesia, in line with recent results and theories. Moreover, we show that at the peak of the specific heat (the critical state), the spin correlations are minimally shaped by the underlying structural network, explaining how the best match between the structure and function is obtained at the onset of criticality, as previously observed. These findings confirm that brain dynamics under anesthesia shows a departure from criticality and could open the way to novel perspectives when the conserved magnetization is interpreted in terms of a homeostatic principle imposed to neural activity.

Motor phenotype is not associated with vascular dysfunction in symptomatic Huntington's disease transgenic R6/2 (160 CAG) mice.

Whereas Huntington's disease (HD) is unequivocally a neurological disorder, a critical mass of emerging studies highlights the occurrence of peripheral pathology like cardiovascular defects in both animal models and humans. The overt impairment in cardiac function is normally expected to be associated with peripheral vascular dysfunction, however whether this assumption is reasonable or not in HD is still unknown. In this study we functionally characterized the vascular system in R6/2 mouse model (line 160 CAG), which recapitulates several features of human pathology including cardiac disease. Vascular reactivity in different arterial districts was determined by wire myography in symptomatic R6/2 mice and age-matched wild type (WT) littermates. Disease stage was assessed by using well-validated behavioural tests like rotarod and horizontal ladder task. Surprisingly, no signs of vascular dysfunction were detectable in symptomatic mice and no link with motor phenotype was found.

Characterizing the Extent of Spatially Integrated Floodplain and Wetland Systems in the White River, Indiana, USA.

Floodplain delineation may inform protection of wetland systems under local, state, or federal laws. Nationally available Federal Emergency Management Agency Flood Insurance Rate Maps (FIRMs, "100-year floodplain" maps) focus on urban areas and higher-order river systems, limiting utility at large scales. Few other national-scale floodplain data are available. We acquired FIRMs for a large watershed and compared FIRMs to floodplain and integrated wetland area mapping methods based on (1) geospatial distance, (2) geomorphic setting, and (3) soil characteristics. We used observed flooding events (OFEs) with recurrence intervals of 25-50 to >100 years to assess floodplain estimate accuracy. FIRMs accurately reflected floodplain areas based on OFEs and covered 32% of river length, whereas soil-based mapping was not as accurate as FIRMs but characterized floodplain areas over approximately 65% of stream length. Geomorphic approaches included more areas than indicated by OFE, whereas geospatial approaches tended to cover less area. Overall, soil-based methods have the highest utility in determining floodplains and their integrated wetland areas at large scales due to the use of nationally available data and flexibility for regional application. These findings will improve floodplain and integrated wetland system extent assessment for better management at local, state, and national scales.

Depressive Symptoms Correlate with Disability and Disease Course in Multiple Sclerosis Patients: An Italian Multi-Center Study Using the Beck Depression Inventory.

BACKGROUND: Depression occurs in about 50% of patients with multiple sclerosis. The aims of this study was to investigate the prevalence of depressive symptoms in a multicenter MS population using the Beck Depression Inventory II (BDI II) and to identify possible correlations between the BDI II score and demographic and clinical variables. METHODS: Data were collected in a multi-center, cross-sectional study over a period of six months in six MS centers in Italy using BDI II. RESULTS: 1,011 MS patients participated in the study. 676 subjects were female, with a mean age of 34 years (SD 10.8), mean EDSS of 3.3 (0-8.5) and mean disease duration of 10.3 years (range 1-50 years). 668 (%) subjects scored lower than 14 on the BDI II and 343 (33.9%) scored greater than 14 (14 cut-off score). For patients with BDI>14 multivariate analysis showed a significant difference between EDSS and disease course. BDI II scores for subjects with secondary progressive (SP) MS were significantly different from primary progressive (PP) patients (p < 0.001) but similar to relapsing-remitting (RR) patients. Considering subjects with moderate to severe depressive symptoms (BDI II score from 20-63), in relation to disease course, 11.7% (83/710) had RR MS, 40.7% (96/236) SP and 13.6% (6/44) PP. CONCLUSIONS: Using the BDI II, 30% of the current sample had depressive symptoms. BDI II score correlates with disability and disease course, particularly in subjects with SP MS. The BDI II scale can be a useful tool in clinical practice to screen depressive symptoms in people with MS.

Function-structure connectivity in patients with severe brain injury as measured by MRI-DWI and FDG-PET.

A vast body of literature exists showing functional and structural dysfunction within the brains of patients with disorders of consciousness. However, the function (fluorodeoxyglucose FDG-PET metabolism)-structure (MRI-diffusion-weighted images; DWI) relationship and how it is affected in severely brain injured patients remains ill-defined. FDG-PET and MRI-DWI in 25 severely brain injured patients (19 Disorders of Consciousness of which 7 unresponsive wakefulness syndrome, 12 minimally conscious; 6 emergence from minimally conscious state) and 25 healthy control subjects were acquired here. Default mode network (DMN) function-structure connectivity was assessed by fractional anisotropy (FA) and metabolic standardized uptake value (SUV). As expected, a profound decline in regional metabolism and white matter integrity was found in patients as compared with healthy subjects. Furthermore, a function-structure relationship was present in brain-damaged patients between functional metabolism of inferior-parietal, precuneus, and frontal regions and structural integrity of the frontal-inferiorparietal, precuneus-inferiorparietal, thalamo-inferioparietal, and thalamofrontal tracts. When focusing on patients, a stronger relationship between structural integrity of thalamo-inferiorparietal tracts and thalamic metabolism in patients who have emerged from the minimally conscious state as compared with patients with disorders of consciousness was found. The latter finding was in line with the mesocircuit hypothesis for the emergence of consciousness. The findings showed a positive function-structure relationship within most regions of the DMN. Hum Brain Mapp 37:3707-3720, 2016. © 2016 Wiley Periodicals, Inc.