Abnormal cerebellar connectivity and plasticity in isolated cervical dystonia.

There is increasing evidence that supports the role of the cerebellum in the pathophysiology of dystonia. We used transcranial magnetic stimulation to test the hypothesis that patients with cervical dystonia may have a disrupted cerebellar cortical connectivity at rest, and that cerebellar plasticity is altered too. We enrolled 12 patients with isolated cervical dystonia and 13 controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right cerebellum and the left primary motor area. Changes in the amplitude of motor evoked potentials were analysed. Continuous and intermittent Theta Burst Stimulation over the cerebellum was also applied. The effects of these repetitive protocols on cortical excitability, on intra-cortical circuits and on cerebellar cortical inhibition were analysed. In healthy subjects, but not in dystonic patients, a conditioning stimulus over the cerebellum was able to inhibit the amplitude of the motor evoked potentials from primary motor cortex. In healthy subjects continuous and intermittent cerebellar Theta Burst Stimulation were able to decrease and increase respectively motor cortex excitability. Continuous Theta Burst Stimulation was able to abolish the cerebellar cortical inhibition observed in basal condition. These effects were not observed in patients with cervical dystonia. Cerebellar cortical connectivity and cerebellar plasticity is altered at rest in patients with cervical dystonia.

Trait- and state-dependent cortical inhibitory deficits in bipolar disorder.

OBJECTIVES: Euthymic patients with bipolar disorder (BD) have deficits in cortical inhibition. However, whether cortical inhibitory deficits are trait- or state-dependent impairments is not yet known and their relationship with psychiatric symptoms is not yet understood. In the present study, we examined trait- and state-dependent cortical inhibitory deficits and evaluated the potential clinical significance of these deficits. METHODS: Nineteen patients with bipolar I disorder were evaluated using the paired-pulse transcranial stimulation protocol, which assessed cortical inhibition during an acute manic episode. Cortical inhibition measures were compared with those obtained in 28 demographically matched healthy controls. A follow-up assessment was performed in 15 of these patients three months later, when there was remission from their mood and psychotic symptoms. The association between cortical inhibitory measures and severity of psychiatric symptoms was also studied. RESULTS: During mania, patients showed decreased short-interval intracortical and transcallosal inhibition, as well as a normal cortical silent period and long-interval cortical inhibition. These findings were the same during euthymia. Symptoms associated with motor hyperactivity were correlated negatively with the degree of cortical inhibition. These correlations were not significant when a Bonferroni correction was applied. CONCLUSIONS: The present longitudinal study showed cortical inhibitory deficits in patients with BD, and supports the hypothesis that cortical inhibitory deficits in BD are trait dependent. Further research is necessary to confirm the clinical significance of these deficits.

Aberrant cortical associative plasticity associated with severe adult Tourette syndrome.

BACKGROUND: Recent studies have shown altered cortical plasticity in adult patients with Tourette syndrome. However, the clinical significance of this finding remains elusive. METHODS: Motor cortical plasticity was evaluated in 15 adult patients with severe Tourette syndrome and 16 healthy controls using the paired associative stimulation protocol by transcranial magnetic stimulation. Associations between paired associative stimulation-induced plasticity and relevant clinical variables, including cortical excitability, psychiatric comorbidities, drug treatment and tic severity, were assessed. RESULTS: Motor cortical plasticity was abnormally increased in patients with Tourette syndrome compared with healthy subjects. This abnormal plasticity was independently associated with tic severity. CONCLUSION: Patients with severe Tourette syndrome display abnormally increased cortical associative plasticity. This aberrant cortical plasticity was associated with tic severity, suggesting an underlying mechanism for tic pathophysiology.

Parieto-motor cortical dysfunction in primary cervical dystonia.

BACKGROUND: Dystonia is considered as a motor network disorder involving the dysfunction of the posterior parietal cortex, a region involved in preparing and executing reaching movements. OBJECTIVE/HYPOTHESIS: We used transcranial magnetic stimulation to test the hypothesis that cervical dystonic patients may have a disrupted parieto-motor connectivity. METHODS: We enrolled 14 patients with primary cervical dystonia and 14 controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right posterior parietal cortex and the right primary motor area. Changes in the amplitudes of motor evoked potential were analyzed as an index of parieto-motor effective connectivity. Patients and healthy subjects were also evaluated with a reaching task. Reaction and movement times were measured. RESULTS: In healthy subjects, but not in dystonic patients, there was a facilitation of motor evoked potential amplitudes when the conditioning parietal stimulus preceded the test stimulus applied over the primary motor area by 4 ms. Reaction and movement times were significantly slower in patients than in controls. In dystonic patients, the relative strength of parieto-motor connectivity correlated with movement times. CONCLUSIONS: Parieto-motor cortical connectivity is impaired in cervical dystonic patients. This neurophysiological trait is associated with slower reaching movements.

Effects of two weeks of cerebellar theta burst stimulation in cervical dystonia patients.

Dystonia is generally regarded as a disorder of the basal ganglia and their efferent connections to the thalamus and brainstem, but an important role of cerebellar-thalamo-cortical (CTC) circuits in the pathophysiology of dystonia has been invoked. Here in a sham controlled trial, we tested the effects of two-weeks of cerebellar continuous theta burst stimulation (cTBS) in a sample of cervical dystonia (CD) patients. Clinical evaluations were performed by administering the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). We used TMS to measure the inhibitory connectivity between the cerebellum and the contralateral motor cortex (cerebellar brain inhibition [CBI]), and the excitability of the contralateral primary motor cortex assessing intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). Paired associative stimulation (PAS) was tested to evaluate the level and the topographical specificity of cortical plasticity, which is abnormally enhanced and non-focal in CD patients. Two weeks of cerebellar stimulation resulted in a small but significant clinical improvement as measured by the TWSTRS of approximately 15%. Cerebellar stimulation modified the CBI circuits and reduced the heterotopic PAS potentiation, leading to a normal pattern of topographic specific induced plasticity. These data provide novel evidence CTC circuits could be a potential target to partially control some dystonic symptoms in patients with cervical dystonia.

Study of cerebello-thalamocortical pathway by transcranial magnetic stimulation in Parkinson's disease.

BACKGROUND: Although functional changes in the activation of the cerebellum in Parkinson's disease (PD) patients have been consistently described, it is still debated whether such altered cerebellar activation is a natural consequence of PD pathophysiology or rather it involves compensatory mechanisms. OBJECTIVE/HYPOTHESIS: We used different forms of cerebellar transcranial magnetic stimulation to evaluate the hypothesis that altered cerebello-cortical interactions can be observed in PD patients and to evaluate the role of dopaminergic treatment. METHODS: We studied the effects of a single cerebellar magnetic pulse over the excitability of the contralateral primary motor cortex tested with motor-evoked potentials (MEPs) (cerebellar-brain inhibition-CBI) in a group of 16 PD patients with (ON) and without dopaminergic treatment (OFF), and in 16 age-matched healthy controls. Moreover, we also tested the effects of cerebellar continuous theta-burst stimulation (cTBS) on MEP amplitude, short intracortical inhibition (SICI) and short intracortical facilitation (SICF) tested in the contralateral M1 in 13 PD patients in ON and OFF and in 16 age-matched healthy controls. RESULTS: CBI was evident in controls but not in PD patients, even when tested in both ON and OFF conditions. Similarly, cerebellar cTBS reduced MEP amplitude and SICI in controls but not in PD patients under any condition. CONCLUSION(S): These results demonstrate that PD patients have deficient short-latency and long-lasting cerebellar-thalamocortical inhibitory interactions that cannot be promptly restored by standard dopaminergic medication.

Relation between training-induced left ventricular hypertrophy and risk for ventricular tachyarrhythmias in elite athletes.

The aim of this study was to analyze the relation between the magnitude of training-induced left ventricular (LV) hypertrophy and the frequency and complexity of ventricular tachyarrhythmias in a large population of elite athletes without cardiovascular abnormalities. Ventricular tachyarrhythmias are a common finding in athletes, but it is unresolved as to whether the presence or magnitude of LV hypertrophy is a determinant of these arrhythmias in athletes without cardiovascular abnormalities. From 738 athletes examined at a national center for the evaluation of elite Italian athletes, 175 consecutive elite athletes with 24-hour ambulatory (Holter) electrocardiographic recordings (but without cardiovascular abnormalities and symptoms) were selected for the study group. Echocardiographic studies were performed during periods of peak training. Athletes were arbitrarily divided into 4 groups according to the frequency and complexity of ventricular arrhythmias during Holter electrocardiographic monitoring. No statistically significant relation was evident between LV mass (or mass index) and the grade or frequency of ventricular tachyarrhythmias. In addition, a trend was noted in those athletes with the most frequent and complex ventricular ectopy toward lower calculated LV mass. In conclusion, ventricular ectopy in elite athletes is not directly related to the magnitude of physiologic LV hypertrophy. These data offer a measure of clinical reassurance regarding the benign nature of ventricular tachyarrhythmias in elite athletes and the expression of athlete's heart.

Energy cost of walking measurements in subjects with lower limb amputations: a comparison study between floor and treadmill test.

Measuring the energy cost of walking (ECW) is a valid way of assessing the walking efficiency of subjects who were prosthetic users following lower limb amputation. The aim of this study was to determine whether, in these subjects, treadmill and floor ECW measurements are comparable. We tested 24 subjects who had undergone unilateral lower limb amputations for vascular diseases as they walked at a self-selected comfortable speed on the floor and on a treadmill. The tests were conducted at the end of rehabilitative treatment to fit prosthesis. Eight subjects underwent transtibial and 16 transfemoral amputation. The measurements were taken with a portable gas analyzer. The self-selected comfortable speed on the treadmill was significantly lower than that on the floor, where the patients adopted the aid they normally used for walking; oxygen consumption was the same in the two tests. Therefore, for both transtibial and transfemoral patients, ECW was greater during walking on the treadmill. Steady-state heart rate did not differ in the two tests. The data show that the ECW values of the amputated subjects obtained on the treadmill at the end of rehabilitation did not correspond with those they obtained on the floor. The floor test is the one that may better reflect walking with prostheses and aids in everyday life, in subjects with dysvascular lower limb amputation, using the prosthesis for a short time.

Functional status and factors influencing the rehabilitation outcome of people affected by above-knee amputation and hemiparesis.

OBJECTIVES: To evaluate the functional status of people with transfemoral amputation and hemiparesis and to identify the factors that influence rehabilitation outcome after inpatient treatment. DESIGN: Retrospective study. SETTING: Rehabilitation hospital. PARTICIPANTS: Forty-five patients (30 men, 15 women; mean age, 69+/-9y) with intact mental status affected by unilateral transfemoral amputation for vascular disease and mild or moderate hemiparesis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Barthel Index, Barthel Index effectiveness, and Locomotor Capabilities Index (LCI) scores were measured. The following factors were studied: side and cause of amputation, side and severity of hemiparesis, sequence and laterality of dual impairment, time interval between impairments, and hospital length of stay. RESULTS: At discharge, mean Barthel Index and LCI scores +/-1 standard deviation were 79+/-12 and 15+/-5.6, respectively; Barthel Index effectiveness was 55+/-23.8. Only 2 patients ambulated without walking aids. Barthel Index effectiveness was better in patients with mild hemiparesis than in patients with more severe impairment. Ipsilateral localization of dual impairment increased the probability of higher LCI scores. CONCLUSIONS: Selected patients with dual impairment can recover the ability to walk. Severity of hemiparesis and laterality were the 2 clinical factors that had the greatest influence on functional measures.