Andrea Bassi

Interhemispheric differences of hand muscle representation in human motor cortex.

Focal magnetic transcranial stimulation (TCS) is employed for mapping of the motor cortical output to abductor digiti minimi (ADM) muscle. The aim of this study was to evaluate the interhemispheric asymmetries in normals. Motor maps were obtained through motor evoked potentials (MEPs) recordings from ADM muscle in 20 healthy subjects in right and left hemispheres TCS. Measurement of several indexes such as excitability threshold, MEPs amplitude, MEPs latency, and silent period duration did not show differences between the hemispheres. Moreover, no interhemispheric asymmetries were found when the amplitude ratio values were analyzed. The hand motor cortical area, as represented by the number of responsive sites (3.6 vs. 3.5) and the “hot spot” site localization presented a fairly symmetrical organization. Absolute values displayed a relatively wide intersubject variability, while their interhemispheric differences were extremely restricted. This observation can offer a new tool in diagnosing and following up neurological disorders affecting the central motor system, mainly for those concerning monohemispheric lesions.

Discontinuation of Statin Therapy and Clinical Outcome After Ischemic Stroke

Background and Purpose— The majority of patients with previous ischemic stroke are expected to benefit significantly from long-term statin therapy. However, discontinuation of medication therapy frequently occurs in clinical practice. The aim of this study was to assess the impact of discontinued statin therapy on clinical outcome in patients discharged after an acute ischemic stroke. Methods— The study population included 631 consecutive stroke survivors (322 men and 309 women; mean±SD age, 70.2±7.6 years) without clinical evidence of coronary heart disease. All patients were discharged on statin therapy and were followed up for 12 months after the acute ischemic stroke. Results— Within 12 months from discharge, 246 patients (38.9%) discontinued statin therapy; the mean time from discharge to statin discontinuation was 48.6±54.9 days (median time, 30 days; interquartile range, 18 to 55 days). During follow-up, 116 patients died (1-year probability of death=0.18; 95% CI, 0.15 to 0.21). Multivariate analysis demonstrated that after adjustment for all confounders and interactions, statin therapy discontinuation (hazard ratio=2.78; 95% CI, 1.96 to 3.72; P=0.003) was an independent predictor of all-cause 1-year mortality. Conclusions— A large number of patients discontinue their use of statins early after acute stroke. Moreover, patients discontinuing statins have a significantly increased mortality during the first year after the acute cerebrovascular event. These findings suggest that patient care should be improved during the transition from a hospital setting to outpatient primary care.

Prognostic Implications of Right-Sided Insular Damage, Cardiac Autonomic Derangement, and Arrhythmias After Acute Ischemic Stroke

Background and Purpose— Acute stroke is associated with impairment of cardiac autonomic balance and increased incidence of arrhythmias. These abnormalities appear more relevant in the case of involvement of the right insula in the infarct area. The aim of this study was to assess the impact of right-sided insular damage, cardiac autonomic derangement, and arrhythmias on clinical outcome after acute ischemic stroke. Methods— Holter monitoring for 24 hours was performed in 208 consecutive patients with first-ever acute ischemic stroke. Time- and frequency-domain measures of heart rate variability and arrhythmias were considered in all cases. All patients were followed for a 12-month period after the initial event. Results— During the 12-month follow-up period, 48 patients died (1-year probability of death, 0.23; 95% CI, 0.17 to 0.30). Multivariate analysis demonstrated that age (hazard ratio [HR], 1.06; 95% CI, 1.01 to 1.10; P=0.0087), stroke severity on admission (HR, 1.25; 95% CI, 1.13 to 1.39; P=0.0001), presence of right-sided insular damage (HR, 2.01; 95% CI, 1.13 to 1.39; P=0.0187), as well as lower values of the SD of all normal-to-normal RR intervals (HR, 3.32; 95% CI, 1.67 to 6.24; P=0.002), and presence of nonsustained ventricular tachycardia during Holter monitoring (HR, 2.99; 95% CI, 1.58 to 5.67; P=0.0007) were independent predictors of 1-year mortality. Conclusions— The integration of traditional risk stratifiers with autonomic and arrhythmic markers, and the careful search for right-sided insular involvement, may represent an effective approach for identification of stroke patients at risk for early mortality.

Decreased heart rate variability is associated with poststroke depression.

OBJECTIVE Although decreased heart rate variability (HRV) has been well-documented in association with depression after myocardial infarction, this phenomenon has not been studied in patients with stroke. The present study was designed to prospectively assess heart rate in relationship to depression among patients with acute stroke. DESIGN Using 24-hour Holter monitoring, HRV was assessed. SETTING A large university rehabilitation hospital. PARTICIPANTS Patients with first ever stroke and no other severe physical illness, cigarette smoking, or drug therapy that could affect HRV were evaluated over 24 hours for HRV. MEASUREMENTS Patients were evaluated using the Structured Clinical Interview for depression diagnosis. Severity was assessed by the Hamilton Depression Rating Scale. Stroke severity was assessed by the National Institutes of Health Stroke Scale, the Barthel Index, and the Mini- Mental State Exam. The standard deviation (SD) of time in milliseconds of normal to normal beats (SDNN) was the primary measure of HRV. RESULTS Among patients with poststroke major or minor depression (N = 33), the SDNN was 109 +/- 32.6 SD compared with nondepressed patients (N = 16) whose SDNN was 133.9 +/- 40.1 SD (Wilcoxon rank test S = 492, p = 0.048). The SDNN was significantly and independently related to the existence of depression, but no other intergroup differences. CONCLUSIONS These findings, for the first time, have provided some evidence that both major and minor poststroke depression may lead to decreased HRV. Future research in larger groups of patients should determine whether other measures of HRV more specific to sympathetic-parasympathetic tone are decreased in patients with poststroke depression.

Electrophysiological and clinical desensitization to apomorphine administration in parkinsonian patients undergoing stereotaxic neurosurgery.

A decreased motor response after repeated doses of apomorphine is observed in severely affected Parkinsons disease patients. We simultaneously studied clinical symptoms and internal pallidus single unit activity in three parkinsonian patients underlying stereotaxic neurosurgery for deep brain stimulation. In each patient, two closely spaced doses of intraoperatory apomorphine were administered, while recording the same extracellular unit. The reduced clinical effect of the second administration was correlated to a lessened inhibition of the pallidal single unit recorded throughout the double administration. Our data support the proposition that fast postsynaptic desensitization to dopamine agonists may take place in the basal ganglia nuclei and play a role in the physiopathology of levodopa long-term treatment syndrome.

Spontaneous sleep modulates the firing pattern of Parkinsonian subthalamic nucleus

In Parkinson’s disease, the subthalamic nucleus (STN) is a common target for functional neurosurgery. Recent investigations have suggested that physiological non-motor stimuli may dramatically alter STN firing properties. By maintaining long-lasting micro-recordings of STN single units in Parkinson’s disease (PD) patients, here we show that the neurons that are responsive to passive movements are also strongly modulated by altered vigilance state (awake vs. sleep). In addition, sleep was characterized by a distinctive irregular train-like firing pattern. These findings suggest that the reduction of the somato-sensory input modifies rigidity and, hence, STN discharge mode. Further, it is suggested that specific STN electrophysiological features are potential targets for future therapeutic interventions.

Gender-Specific Predictors of Functional Outcome after Stroke Rehabilitation: Potential Role of the Autonomic Nervous System

The aim of this study was to assess the impact of cardiac autonomic derangement on gender-associated functional outcome of patients with subacute ischemic stroke undergoing a hospital-based rehabilitation program. The study population included 126 consecutive first-ever stroke survivors (mean age 59.7 ± 11.6 years). Time-domain measures of heart rate variability (HRV) by 24-hour Holter monitoring (HM) were considered in all cases. By the end of the rehabilitation program an unfavorable functional outcome with dependency (Barthel Index score of <75) was found in 27 men (40.3%) and in 31 women (52.5%; p = 0.168). Multivariate analysis demonstrated that high age, low Barthel Index score and low Rankin Scale score on admission were independent predictors of an unfavorable functional outcome in both men and women. The standard deviation of normal-to-normal RR intervals on HM was an independent predictor of rehabilitation outcome only in men (OR 15.29, 95% CI 2.47–46.58, p = 0.001). The presence of insular damage on neuroimaging studies was independently associated with an unfavorable functional outcome only in female (OR 18.89, 95% CI 2.34–71.4, p = 0.006). HRV does not predict functional outcome after rehabilitation in women. Instead, insular damage appears to have a role in determining the final results of rehabilitation in women but not in men.

Temporal administration of entacapone with slow release L-dopa: pharmacokinetic profile and clinical outcome.

Abstract.Entacapone is a specific, peripherally acting catechol-O-methyltransferase (COMT) inhibitor that prevents peripheral degradation of L-dopa, thus improving its bioavailability. Entacapone is known to have pharmacokinetics similar to standard L-dopa but not to that of controlled-release (CR) L-dopa. The aim was to determine whether delayed entacapone administration may prolong CR L-dopa half-life in comparison to the co-administration modality. We compared plasma L-dopa concentrations after co-administration of CR L-dopa and entacapone or after administration of CR and a delayed (30 and 90 minutes) entacapone dose in 10 parkinsonian patients. The area under the concentration-time curve and other pharmacokinetic parameters were not changed by the delayed administration of entacapone. Different temporal modalities of entacapone administration had similar effects on CR L-dopa pharmacokinetics and on L-dopa-induced clinical improvement.

Dbs in Parkinsonian Subthalamic Nucleus: Electrophysiological and Biochemical Changes

Deep brain stimulation (DBS) of subthalamic nucleus (STN) or internal globus pallidus (GPi) represents a valid strategy in the treatment of medically refractory parkinsonian patients. The mechanisms that explain the efficacy of DBS are still a matter of debate. Here, we examine the early effects promoted, in GPi, by DBS delivered in STN. Surprisingly, although a clear clinical improvement occurred, no change of GPi firing activity was detected in the four tested patients. In two out of these four patients, the extracellular content of GABA and glutamate, assessed by microdialysis probes in GPi, was unaltered suggesting the lack of changes in the synaptic release of endogenous aminoacids in the STN-GPi pathway. In contrast, the concentrations of cyclic guanosine monophosphate (cGMP), evaluated in the other two patients, consistently and irreversibly increased following DBS. These results emphasize the possibility that the clinical effectiveness of STN DBS may derive from a direct impact on pallidofugal fibers close to the nucleus, even in the absence of electrophysiological changes of GPi firing frequency.