Leandro Provinciali

Transcranial direct current stimulation improves word retrieval in healthy and nonfluent aphasic subjects

A number of studies have shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) affects performances of both healthy and brain-damaged subjects. In this study, we investigated the potential of tDCS to enhance associative verbal learning in 10 healthy individuals and to improve word retrieval deficits in three patients with stroke-induced aphasia. In healthy individuals, tDCS (20 min, 1 mA) was applied over Wernickes area (position CP5 of the International 10–20 EEG System) while they learned 20 new “words” (legal nonwords arbitrarily assigned to 20 different pictures). The healthy subjects participated in a randomized counterbalanced double-blind procedure in which they were subjected to one session of anodic tDCS over left Wernickes area, one sham session over this location and one session of anodic tDCS stimulating the right occipito-parietal area. Each experimental session was performed during a different week (over three consecutive weeks) with 6 days of intersession interval. Over 2 weeks, three aphasic subjects participated in a randomized double-blind experiment involving intensive language training for their anomic difficulties in two tDCS conditions. Each subject participated in five consecutive daily sessions of anodic tDCS (20 min, 1 mA) and sham stimulation over Wernickes area while they performed a picture-naming task. By the end of each week, anodic tDCS had significantly improved their accuracy on the picture-naming task. Both normal subjects and aphasic patients also had shorter naming latencies during anodic tDCS than during sham condition. At two follow-ups (1 and 3 weeks after the end of treatment), performed only in two aphasic subjects, response accuracy and reaction times were still significantly better in the anodic than in the sham condition, suggesting a long-term effect on recovery of their anomic disturbances.

Cerebrovascular Reactivity and Cognitive Decline in Patients With Alzheimer Disease

Background and Purpose— The aim of this study was to explore the possible contribution of alterations in cerebral hemodynamics to the evolution of cognitive impairment in patients with Alzheimer disease (AD). Method— Fifty-three patients with AD were investigated. The evolution of cognitive decline over 12 months was evaluated by means of changes in Mini Mental State Examination (MMSE) and AD Assessment Scale for Cognition (ADAS-Cog) scores. Demographic characteristics, vascular risk profile, pharmacological treatment, and presence of white matter lesions were assessed at entry. Further, a basal evaluation of cerebrovascular reactivity to hypercapnia was measured with transcranial Doppler ultrasonography using the breath-holding index (BHI). Results— Of all the variables considered, both MMSE and ADAS-Cog changes had the highest correlation with BHI, followed by age and diabetes. After subdividing both cognitive measures reductions into bigger and smaller-than-average decline (2 points for MMSE; 5 points for ADAS-Cog), multiple logistic regression indicated BHI as the sole significant predictor of cognitive decline. Conclusions— These results show an association between impaired cerebral microvessels functionality and unfavorable evolution of cognitive function in patients with AD. Further research is needed to fully establish whether altered cerebral hemodynamics may be considered an independent factor in sustaining cognitive decline progression or an effect of pathological processes involved in AD.

Monoamine Oxidase-A Genetic Variations Influence Brain Activity Associated with Inhibitory Control: New Insight into the Neural Correlates of Impulsivity

BACKGROUND Previous evidence has shown that genetic variations in the serotonergic system contribute to individual differences in personality traits germane to impulse control. The monoamine oxidase-A (MAO-A) gene, coding for an enzyme primarily involved in serotonin and noradrenaline catabolism, presents a well-characterized functional polymorphism consisting of a variable number of tandem repeats in the promoter region, with high-activity and low-activity variants. High-activity allele carriers have higher enzyme expression, lower amine concentration, and present higher scores on behavioral measures of impulsivity than low-activity allele carriers. METHODS We studied the relationship of this polymorphism to brain activity elicited by a response inhibition task (Go/NoGo task), using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging in 24 healthy men. RESULTS Direct comparison between groups revealed a greater BOLD response in the right ventrolateral prefrontal cortex (Brodmanns area [BA] 45/47) in high-activity allele carriers, whereas a greater response in the right superior parietal cortex (BA 7) and bilateral extrastriate cortex (BA 18) was found in low-activity allele carriers. CONCLUSIONS These data suggest that a specific genetic variation involving serotonergic catabolism can modulate BOLD response associated with human impulsivity.

Predictive value of clinical indices in detecting aspiration in patients with neurological disorders

OBJECTIVES (1) To evaluate the predictive value of a detailed clinical screening of aspiration in patients withneurological diseases, both with and without symptoms of dysphagia taking videofluoroscopy as the gold standard; (2) to assess the existence of risk factors for silent aspiration, measuring the cost-benefit ratio of radiological examination. METHODS 93 consecutive patients meeting the diagnostic criteria for a neurological disease with a risk of swallowing dysfunctions (cerebrovascular accidents, brain injury, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, myotonic dystrophy, and abiotrophic diseases) underwent a detailed clinical assessment using a 25 item form to check for symptoms of dysphagia and impairment of the oropharyngeal swallowing mechanism. The 3 oz water swallow test was also performed to assess the aspiration risk. Sensitivity, specificity, positive predictive, and negative predictive values (NPV) of dysphagia, history of cough on swallowing, and 3 oz test positivity, versus videofluoroscopy documented aspiration, taken as the gold standard, were measured in all the patients and in subgroups with different neurological disorders. RESULTS Non-specific complaints of dysphagia showed a very poor predictive value, whereas the symptom “cough on swallowing” proved to be the most reliable in predicting the risk of aspiration, with 74% sensitivity and specificity, 71% positive predictive, and 77% negative predictive value. The standardised 3-oz test had a higher predictive potential than the clinical signs, but had low sensitivity. The association of cough on swallowing with the 3 oz test gave a positive predictive of 84%, and an negative predictive value of 78%. In cases where the clinical tests failed to detect any impairment, videofluoroscopy documented only a low risk (20%) for mild aspiration. CONCLUSIONS The association of two clinical items (such as history of cough on swallowing and 3 oz test positivity) provides a useful screening tool, the cost:benefit ratio of which seems very competitive in comparison with videofluoroscopy in aspiration risk evaluation.

Botulinum toxin type A for drooling in Parkinson's disease: a double-blind, randomized, placebo-controlled study.

To investigate the safety and efficacy of botulinum toxin type A (BoNTX) treatment to reduce sialorrhea in Parkinsons disease (PD), a double‐blind, randomized, placebo‐controlled study enrolled 32 PD patients complaining of excessive drooling. Patients received either 50 U Botox in each parotid gland or placebo without using ultrasound guidance. Subjects treated with BoNTX experienced a reduction in both drooling frequency and familial and social disability (Time × Group effect: P < 0.01), as well as in saliva production (Time × Group effect: P < 0.0001). No adverse events were recorded. BoNTX injections are safe and effective treatment for the management of PD‐related drooling.

Low-dose botulinum toxin with ankle taping for the treatment of spastic equinovarus foot after stroke

OBJECTIVE To evaluate the efficacy of a combined treatment for spastic foot using selective injections of botulinum toxin (BTA) into the tibialis posterior muscle followed by ankle taping, and to compare it with current BTA treatment procedure. DESIGN Single-blind randomized control trial. Three-month follow-up after treatment. SETTING Neurorehabilitation clinic. SUBJECTS Eighteen outpatients with equinovarus foot due to severe spasticity after stroke. INTERVENTIONS (1) Injection of 190 to 320 BTA U into several calf muscles (group A); (2) injection of 100 BTA U into the tibialis posterior muscle, followed by ankle-foot taping (group B). MAIN OUTCOME MEASURES Ankle range of motion (ROM), Ashworth scale, gait velocity, and step length. RESULTS Average Ashworth scores decreased 1 point in both groups, but the benefit appeared of shorter duration in group B. Changes in both foot position at rest and passive ankle ROM were observed in all patients, without treatment-related differences, except for gain in passive dorsiflexion that appeared higher in group A. Gait velocity and step length showed similar increases in both groups. CONCLUSION The combination of selective injections of low BTA doses with ankle-foot taping is as effective as the injection of the current doses for the reduction of foot inversion with positive effects on gait parameters.

Low-frequency rTMS promotes use-dependent motor plasticity in chronic stroke A randomized trial

Objective: To investigate the long-term behavioral and neurophysiologic effects of combined time-locked repetitive transcranial magnetic stimulation (rTMS) and physical therapy (PT) intervention in chronic stroke patients with mild motor disabilities. Methods: Thirty patients were enrolled in a double-blind, randomized, single-center clinical trial. Patients received 10 daily sessions of 1 Hz rTMS over the intact motor cortex. In different groups, stimulation was either real (rTMSR) or sham (rTMSS) and was administered either immediately before or after PT. Outcome measures included dexterity, force, interhemispheric inhibition, and corticospinal excitability and were assessed for 3 months after the end of treatment. Results: Treatment induced cumulative rebalance of excitability in the 2 hemispheres and a reduction of interhemispheric inhibition in the rTMSR groups. Use-dependent improvements were detected in all groups. Improvements in trained abilities were small and transitory in rTMSS patients. Greater behavioral and neurophysiologic outcomes were found after rTMSR, with the group receiving rTMSR before PT (rTMSR-PT) showing robust and stable improvements and the other group (PT-rTMSR) showing a slight improvement decline over time. Conclusion: Our findings indicate that priming PT with inhibitory rTMS is optimal to boost use-dependent plasticity and rebalance motor excitability and suggest that time-locked rTMS is a valid and promising approach for chronic stroke patients with mild motor impairment. Classification of evidence: This interventional study provides Class I evidence that time-locked rTMS before or after physical therapy improves measures of dexterity and force in the affected limb in patients with chronic deficits more than 6 months poststroke. Neurology® 2012;78:256–264

Long-term efficacy and safety of pramipexole in advanced Parkinson's disease: Results from a European multicenter trial

A double‐blind, placebo‐controlled study with a subsequent open‐label phase was conducted in 354 patients with Parkinsons disease (PD) and motor fluctuations under individually adjusted therapy with levodopa. During the double‐blind phase 174 patients received pramipexole and 180 placebo. In agreement with previous studies, pramipexole treatment improved UPDRS sum scores of parts II and III by 30% and off times by approximately 2.5 hours per day. Differences between the treatment groups became significant at a daily dose of 0.75 mg of pramipexole dihydrochloride. We, furthermore, performed post hoc analyses with respect to resting tremor and depression. Patients with pronounced resting tremor derived a clear benefit from pramipexole treatment compared with placebo. In addition, pramipexole significantly improved the subitems motivation/initiative and depression in a subpopulation with increased Unified Parkinsons Disease Rating Scale I scores at the time of inclusion. There were 262 patients who were subsequently enrolled into the open‐label study featuring a maximum duration of up to 57 months. Statistical analysis revealed good long‐term efficacy and tolerability of pramipexole. Overall, only a low prevalence of somnolence was found. In summary, this study provides additional level I evidence of the usefulness of pramipexole, suggests a particular tremorlytic and a possible antidepressant action of this compound, and addresses for the first time its efficacy and safety during long‐term administration in advanced PD.

Post-stroke spasticity management with repeated botulinum toxin injections in the upper limb.

OBJECTIVE Although the botulinum toxin A (BTX-A) treatment has proved effective in spasticity management, no information is available with regard to the effects of repeated injections over time. DESIGN To evaluate the effects of BTX-A on moderate or severe upper limb spasticity, an exploratory investigation was performed on 28 stroke patients treated for 2 yr or longer and observed for 3 yr. Every 3 to 5 mo, each patient received BTX-A injections in upper limb muscles. The assessment, performed before and 1 mo after each injection for a median of 28 mo, included technical and functional objectives and the burden of care. The former were evaluated by using the modified Ashworth Scale for spasticity and the goniometric measurement of rest position and range of motion; functional objectives were evaluated by means of the Frenchay Arm Test and a patient/caregiver goals assessment scale. RESULTS BTX-A treatment was followed by an improvement in all technical outcome measures. Motor dexterity scores improved in only 8 of 28 patients, vs. daily living activities, which increased in all subjects. Although the average dosage injected per session did not change, intervals between injections became longer. No relationship between either spasticity onset or residual motoricity and response to treatment could be found. CONCLUSIONS This investigation is relevant clinically because repeated BTX-A injections show unchanging effectiveness in the management of focal spasticity after stroke.

A multidimensional assessment of multiple sclerosis: relationships between disability domains

Objective ‐ i) To test the feasibility of a multidimensional assessment based on both task‐related and self‐evaluation questionnaire scores in patients with multiple sclerosis (MS); ii) to correlate the results from selective measures with the severity of illness in terms of the Expanded Disability Status Scale (EDSS) score; iii) to assess the relationships between different domains of MS‐related disability and handicap. Patients and methods ‐ Eighty‐three MS patients (M/F 31/52; age 43.26±10.9 years, range 21–72) underwent a standard clinical evaluation of motor abilities (by means of the Rivermead Mobility index, Timed Walking Test, Nine Hole Peg test and Hauser Ambulation Index) and cognitive performances (using Digit Symbol, Buschke‐Fuld selective remind test, “FAS” Word Fluency, Wisconsin Card Sorting test and Block design test). The Beck Depression inventory, MS Specific Fatigue Scale, Functional Assessment of MS and London Handicap Scale were applied to evaluate mood, fatigue, quality of life and handicap, respectively. Minimal Record of Disability measures ‐ MRD (i.e. EDSS, Inability Status Scale and Environmental Status Scale) were also applied to test the criterion validity of the selected disability and handicap scales. The Kruskal‐Wallis H‐test for independent samples tested differences between subgroups with an increasing EDSS score (<3.5, 3.5–6.0, >6.0). The covariance and redundancy of measures included in the multidimensional assessment were evaluated through Factor Analysis. The Multiple Regression Analysis was used to detect the relative impact of either motor or cognitive disabilities and depression on handicap and quality of life. Results ‐ The multimodal assessment took 70 min on average to be performed, being well accepted by patients. Motor abilities worsened as the EDSS score rose, unlike cognitive performances which proved to be similarly impaired at different severity levels. Measures of fatigue and depression were not related to EDSS values. The chosen measures were assigned by Factor Analysis to 4 domains corresponding to motor performance, executive performance, cognitive abilities and quality of life, respectively. Regression analysis showed how handicap and depression independently affect quality of life. While the handicap score is mostly influenced by motor ability, as measured by the Rivermead Mobility Index, the depression score grows independently of any physical or cognitive disability and seems to be related to fatigue self‐assessment scores. Conclusions ‐ A multidimensional approach to MS patient assessment allows a more detailed and sensitive evaluation of their disability profile and perceived difficulties, leading to a care programme tailored to the patients needs.