Neuroplasticity and brain reorganization associated with positive outcomes of multidisciplinary rehabilitation in progressive multiple sclerosis: A fMRI study.

BACKGROUND: Multiple sclerosis (MS) is characterized by a range of symptoms, including motor, sensorimotor and cognitive impairments, that limit the quality of life. A multidisciplinary rehabilitation approach in people affected by multiple sclerosis was recently reported to improve the functional abilities of MS patients in daily activities. The purpose of the study was to assess the effect of multidisciplinary rehabilitation on the whole brain of MS patients by means of functional magnetic resonance imaging (fMRI). METHODS: Thirty individuals affected by MS (49.9 ± 12.1 years; disease duration: 16.0 ± 8.5 years) with a medium-high severity of disease were enrolled. The fMRI examination assessed a range of action-related tasks involving passive movement, mental simulation of action and miming of action triggered by external stimuli, such as object photography. The three tasks were performed using each arm separately. The fMRI acquisitions were performed at T1 (inclusion in the study), T2 (3 months later, at the start of rehabilitation) and T3 (after 3 months of multidisciplinary rehabilitation). RESULTS: The fMRI results revealed a significant reduction in the activity of brain areas related to task-specific networks as well as the activation of cerebral regions not usually involved in task-specific related network, such as the medial prefrontal area. CONCLUSIONS: The effectiveness of multidisciplinary rehabilitation on activity and participation has been established in previous studies. Our study sheds new light on the effect of such treatment on brain reorganization.

Evaluation of the Impact of Cognitive Training on Quality of Life in Patients with Multiple Sclerosis.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of cognitive rehabilitation in a group of multiple sclerosis (MS) patients. METHODS: Thirty-four patients were included in this study and randomly allocated either to treatment with multidisciplinary rehabilitation plus cognitive training or to treatment with multidisciplinary rehabilitation alone. RESULTS: After 3 months of cognitive treatment, the patients assigned to the rehabilitation plus cognitive training group displayed an improvement in the cognitive test of executive function and a marked improvement in quality of life (QoL). The patients treated with multidisciplinary rehabilitation without cognitive training improved in the physical composite score alone. Both groups of patients displayed an improvement in depression, though the improvement was confirmed at the 6-month follow-up examination (p = 0.036) only in patients treated with multidisciplinary rehabilitation plus cognitive training. CONCLUSIONS: Our results indicate that the multidisciplinary rehabilitation treatment is the best approach to treat MS. The specific effect of each treatment needs to be assessed to be able to determine its role within a multidisciplinary approach. Cognitive rehabilitation is an important aspect of this multidisciplinary approach insofar as it may improve the QoL of MS people.

Does robot-assisted gait training improve ambulation in highly disabled multiple sclerosis people? A pilot randomized control trial.

BACKGROUND: Robotic training is commonly used to assist walking training in patients affected by multiple sclerosis (MS) with non-conclusive results. OBJECTIVE: To compare the effect of robot-assisted gait training (RAGT) with that of conventional walking training (CWT) on gait competencies, global ability, fatigue and spasticity in a group of severely affected patients with MS. METHODS: A pilot, single-blind randomized controlled trial was conducted in 43 severe (Expanded Disability Status Scale (EDSS) score of 6-7.5) and non-autonomous ambulant in-patients with MS. Experimental group performed 12 sessions of RAGT, whereas control group performed the same amount of CWT. Primary outcome measures were gait ability assessed by 2 minutes walking test and Functional Ambulatory Category; secondary outcomes were global ability (modified Barthel Index), global mobility (Rivermead Mobility Index), severity of disease (EDSS) and subjectively perceived fatigue (Fatigue Severity Scale). RESULTS: The number of subjects who achieved a clinical significant improvement was significantly higher in RAGT than in CWT ( p < 0.05 for both primary outcome measures). RAGT also led to an improvement in all the other clinical parameters (global ability: p < 0.001, global mobility: p < 0.001, EDSS: p = 0.014 and fatigue: p = 0.001). CONCLUSIONS: RAGT improved the walking competencies in non-autonomous ambulant patients with MS, with benefits in terms of perceived fatigue.

Chronic Pain in Multiple Sclerosis Patients: Utility of Sensory Quantitative Testing in Patients with Fibromyalgia Comorbidity.

BACKGROUND: Lower thermal and discomfort thresholds may predispose multiple sclerosis (MS) patients to chronic pain, but a possible effect of fibromyalgia (FM) comorbidity has never been investigated. Aims were to investigate the thermal and discomfort thresholds in the evaluation of pain intensity between MS patients with FM (PFM+) and MS patients with pain not associated to FM (PFM-). METHODS: One hundred thirty three MS patients were investigated for chronic pain. FM was assessed according to the 1990 ACR diagnostic criteria. An algometer was used to measure the thresholds in the patients and 60 matched healthy subjects. RESULTS: Chronic pain was present in 88 (66.2%) patients; 12 (13.6%) had neuropathic pain, 22 (17.3%) were PFM+ and 65 (48.9%) PFM-. PFM+ were predominantly female (p = 0.03) and had a greater EDSS (p = 0.01) than NoP; no other significant differences emerged than PFM-. The thresholds were lower in MS patients than controls (p < 0.01), mainly in the PFM+. FM severity influenced the thermal threshold (p < 0.001), while the female gender influenced the discomfort threshold (p < 0.001). CONCLUSION: Thermal and discomfort thresholds were lower in patients than controls and were the lowest in PFM+. Their more severely impaired thermal threshold supports a neurophysiological basis of such association.

Inability to Process Negative Emotions in Cerebellar Damage: a Functional Transcranial Doppler Sonographic Study.

Recent studies have implicated the cerebellum as part of a circuitry that is necessary to modulate higher order and behaviorally relevant information in emotional domains. However, little is known about the relationship between the cerebellum and emotional processing. This study examined cerebellar function specifically in the processing of negative emotions. Transcranial Doppler ultrasonography was performed to detect selective changes in middle cerebral artery flow velocity during emotional stimulation in patients affected by focal or degenerative cerebellar lesions and in matched healthy subjects. Changes in flow velocity during non-emotional (motor and cognitive tasks) and emotional (relaxing and negative stimuli) conditions were recorded. In the present study, we found that during negative emotional task, the hemodynamic pattern of the cerebellar patients was significantly different to that of controls. Indeed, whereas relaxing stimuli did not elicit an increase in mean flow velocity in any group, negative stimuli increased the mean flow velocity in the right compared with left middle cerebral artery only in the control group. The patterns by which mean flow velocity increased during the motor and cognitive tasks were similar within patients and controls. These findings support that the cerebellum is part of a network that gives meaning to external stimuli, and this particular involvement in processing negative emotional stimuli corroborates earlier phylogenetic hypotheses, for which the cerebellum is part of an older circuit in which negative emotions are crucial for survival and prepare the organism for rapid defense.

Chronic pain in multiple sclerosis: is there also fibromyalgia? An observational study.

BACKGROUND: Chronic pain is common in persons with multiple sclerosis (MS), but the co-morbidity of fibromyalgia (FM) has yet to be investigated in MS. Objectives of the study were to evaluate, among the various types of chronic pain, the frequency of FM in MS and its impact on MS patients' health-related quality of life (HRQoL). MATERIAL AND METHODS: 133 MS patients were investigated for the presence and characterization of chronic pain within 1 month of assessment. A rheumatologist assessed the presence FM according to the 1990 ACR diagnostic criteria. Depression, fatigue, and HRQoL were also assessed by means of specific scales. RESULTS: Chronic pain was present in 66.2% of patients (musculoskeletal in 86.3%; neuropathic in 13.7%; absent in 33.8% [called NoP]). Pain was diagnosed with FM (PFM+) in 17.3% of our MS patients, while 48.9% of them had chronic pain not FM type (PFM-); the prevalence of neuropathic pain in these 2 sub-groups was the same. PFM+ patients were prevalently females and had a higher EDSS than NoP. The PFM+ patients had a more pronounced depression than in the NoP group, and scored the worst in both physical and mental QoL. CONCLUSIONS: In our sample of MS patients we found a high prevalence of chronic pain, with those patients displaying a higher disability and a more severe depression. Moreover, FM frequency, significantly higher than that observed in the general population, was detected among the MS patients with chronic pain. FM occurrence was associated with a stronger impact on patients' QoL.

Altered cerebral vasoregulation predicts the outcome of patients with partial anterior circulation stroke.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the correlation between cerebral hemodynamic changes and the evolution of neurological deficit after stroke. METHODS: We included 65 patients with non-lacunar stroke admitted to a rehabilitation hospital within 4 weeks from the event. An evaluation of cerebrovascular reactivity to hypercapnia was performed with transcranial Doppler ultrasonography using the breath-holding index (BHI). Activities of daily living status was measured by the Barthel Index (BI) and impairment of mobility was assessed by means of the Rivermead Mobility Index (RMI). Multivariate analyses were performed using effectiveness of treatment, evaluated on BI and RMI as dependent variables. Independent variables were BHI values, age, sex, length of stay, hypertension, smoking habit, presence of aphasia and neglect, poststroke depression, and the degree of severity of stroke. RESULTS: The effectiveness on BI was associated positively with normal BHI values and with neurological severity at admission, measured by the Canadian Neurological Scale. The regression coefficients for effectiveness on RMI showed that the most relevant predictor was ipsilateral BHI (the slope resulted equal to 5.8), followed by age (a 10-year age difference is expected to diminish the effectiveness by about 4.3%) and by depression (depressed patients have almost 11% less effectiveness than non-depressed patients). CONCLUSION: These findings suggest that a satisfactory recovery from neurologic deficits requires a preserved cerebrovascular reactivity in the lesioned hemisphere despite the presence of an anatomic lesion.

Enhanced-MRI and ultrasound evaluation of painful shoulder in patients after stroke: a pilot study.

BACKGROUND: Epidemiological and radiological studies have previously been performed to identify the possible causes of hemiplegic shoulder pain (HSP). Many different etiologies have been postulated, though no clear correlations have emerged, and a multifactorial pathogenesis of HSP has been proposed. Recently, two MRI-based studies have described different shoulder findings as possible causes of pain in chronic stroke survivors. PURPOSE: The aim of this study was to describe the structural abnormalities of the painful shoulder in the first months after stroke by ultrasound and enhanced MRI. The secondary aims were to identify possible predisposing factors for HSP and to evaluate its impact on motor recovery. METHODS: One hundred and fifty-three first-time stroke patients, admitted to the Santa Lucia Foundation for rehabilitation, were investigated for HSP. Twenty-five stroke patients with HSP and 16 stroke patients without shoulder pain were included. An ultrasound evaluation and enhanced shoulder MRI were performed for all the patients. RESULTS: Among the shoulder abnormalities detected by both imaging studies, only capsulitis, which was detected by enhanced shoulder MRI in 88% of the HSP patients, was independently associated with pain (p < 0.001) and proven to be predictive of pain intensity as expressed by the VAS score (p < 0.003). HSP correlated with a worse global recovery (p < 0.05) as well as with male sex (p = 0.006), neglect (p = 0.02) and subluxation (p = 0.03), although none of these features were found to be independent predictors of pain. CONCLUSION: Adhesive capsulitis was found to be a possible cause of HSP. However, MRI, which is more expensive than other diagnostic tools, may be considered the gold standard tool for understanding the etiology of HSP.

Basilar and middle cerebral artery reactivity in patients with migraine.

BACKGROUND: Migraine has been reported as a possible risk factor for ischemic stroke. The mechanisms underlying this association are unknown. OBJECTIVES: To evaluate cerebrovascular reactivity to hypercapnia in the anterior and posterior circulation of patients with migraine, as reduced cerebrovascular reactivity is associated with a predisposition to stroke in various clinical conditions. METHODS: Using transcranial Doppler ultrasonography, changes in flow velocity during apnea were measured in both middle cerebral arteries and in the basilar artery of 15 control subjects and 30 patients with migraine (15 with aura and 15 without aura) during an attack-free period. Cerebrovascular reactivity was evaluated using the breath-holding index, which is calculated by dividing the percent increase in mean flow velocity recorded during a breath-holding episode by its duration (in seconds) after a normal inspiration. RESULTS: Vascular reactivity in the middle cerebral arteries was similar in patients and controls and significantly lower in the basilar artery of patients with migraine with aura compared with the other 2 groups (P <.0001). CONCLUSIONS: These findings show that in patients with migraine with aura, there is an impairment in the adaptive cerebral hemodynamic mechanisms in the posterior circulation. This fact could have pathogenetic implications since the association between migraine and stroke frequently regards patients with migraine with aura, and cerebral infarcts occur more commonly in the vertebrobasilar district.

Functional outcome of ischemic and hemorrhagic stroke patients after inpatient rehabilitation: a matched comparison.

BACKGROUND AND PURPOSE: The goal of this study was to assess the specific influence of stroke etiology on rehabilitation results. METHODS: This was a case-control study of 270 inpatients with sequelae of first stroke who were enrolled in homogeneous subgroups and matched for stroke severity, basal disability, age (within 1 year), sex, and onset admission interval (within 3 days) who were different only in terms of stroke origin, infarction versus hemorrhage. We compared the groups' length of stay, efficiency and effectiveness of treatment, and percentage of low and high responder patients. Odds ratios of dropouts and of low and high therapeutic response were also quantified. RESULTS: Compared with ischemic patients, hemorrhagic patients had significantly higher Canadian Neurological Scale and Rivermead Mobility Index scores at discharge; higher effectiveness and efficiency on the Canadian Neurological Scale, Barthel Index, and Rivermead Mobility Index; and a higher percentage of high responders on the Barthel Index. Hemorrhagic patients showed a probability of a high therapeutic response on the Barthel Index that was approximately 2.5 times greater than that of ischemic patients (odds ratio, 2.48; 95% confidence interval, 1.19 to 5.20; accuracy on prediction, 87.06%). CONCLUSIONS: The results of this study provide further evidence of better functional prognosis in stroke survivors with hemorrhagic stroke.

Early cerebral hemodynamic changes during passive movements and motor recovery after stroke.

Recovery from hemiplegia is a complex phenomenon that depends on various adaptive processes involving both the affected and the unaffected hemisphere. Our aim in this study was to investigate changes in cerebral perfusion in hemiplegic stroke patients during passive movements and their correlation with the subsequent motor recovery. The study included 30 patients with single, subcortical ischemic cerebral lesions. Within 14 days (range 8 to 14 days) from stroke onset, all patients were examined for the effects of passive elbow movements on cerebral blood flow in the middle cerebral arteries (MCAs) by means of bilateral transcranial Doppler (TCD) ultrasonography. On the same day as TCD assessment, they were also evaluated clinically with the Canadian Neurological Scale (CNS) and with Medical Research Council (MRC) scale for motor deficit of the affected arm. A clinical evaluation using the same scales was repeated after two months of motor rehabilitation therapy. We investigated the relationship between changes of Mean Flow Velocity (MFV) during passive movements and degree of recovery after stroke. The logistic regression procedure indicated that out of all factors considered as possibly related to a good clinical motor deficit recovery of the affected arm, evaluated by means of MRC, only the MFV percentage increase played a predictive role. In particular, for each additional point of contralateral MFV percentage increase during passive movement of the affected arm, the relative probability of good clinical recovery increased 5.68 times (95% CI=1.76-18.40; p=0.004). Similar results were found when the clinical recovery was measured by means of the CNS (slope=0.40, p<0.001). Passive movements in hemiplegic stroke patients before clinical recovery elicit activation patterns that may be critical for the restoration of motor function.I n particular, early and consistent activation of the affected hemisphere, as detected with TCD, seems to predict the positive evolution of a motor deficit.

Aging and stroke rehabilitation. a case-comparison study.

The aim of this study was to assess the specific influence of age on basal functional status and rehabilitation results. We conducted a case-comparison study on 150 stroke inpatients. They were enrolled in homogeneous subgroups, matched for severity of stroke (measured by Canadian Neurological Scale - CNS) and onset admission interval (within 3 days) and divided into five subgroups according to age: or=85 years. Even when severity of stroke was the same, increasing age was associated with greater disability in activities of daily living (ADL) and mobility, minor results of rehabilitation treatment and shorter length of stay. Patients >or=85 years were nearly ten times as likely to show a low response in ADL (OR = 9.28, 95% CI = 2.89-29.76) and nearly six times in mobility (OR = 6.13, 95% CI = 2.18-17.25) than younger patients. However, rehabilitation treatment was efficacious also in patients >or=85 years, with effectiveness of treatment 27.96% on ADL and 18.64% on mobility. On one hand our results confirm the unfavorable influence of age on functional outcome and on the other that inpatient rehabilitation is substantially effective also for very old patients, although less than for younger ones.