Martin Bareš

Pramipexole and pergolide in the treatment of depression in Parkinson's disease:a national multicentre prospective randomized study.

An 8‐month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin®) and pergolide (PRG; Permax®) as add‐on to L‐dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non‐demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinsons disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self – Rating Depression Scale by Zung were evaluated in an open‐label design.

Levodopa-induced dyskinesias and continuous subcutaneous infusions of apomorphine: results of a two-year, prospective follow-up.

Twelve patients with levodopa‐induced dyskinesias were treated with continuous subcutaneous apomorphine. A markedly significant reduction in peak dose dyskinesias occurred over a two‐year follow‐up.

Intracortical inhibition and facilitation are impaired in patients with early Parkinson's disease: a paired TMS study

Twelve patients with early Parkinsons disease (PD), none of whom had received any previous l‐DOPA treatment, but using other antiparkinsonian drugs, were studied using transcranial magnetic stimulation (TMS). Contralateral and ipsilateral hemispheres were examined, with a focus on the more pronounced parkinsonian symptoms. The conditioning‐test TMS paradigm (with a subthreshold conditioning stimulus and a suprathreshold test stimulus) was used through a stimulating round coil. Paired stimuli of short (3, 5 and 7 ms), medium (10, 15 and 20 ms), and long (100, 150, 200 and 250 ms) interstimulus intervals (ISI) were pseudo‐randomly mixed with a single stimulus. The first interosseus muscle was used for the motor‐evoked potential recordings. Ten healthy subjects (age and sex matched) were studied in the same manner to obtain normative data. When both groups were compared, the significant difference (reduction of the intracortical inhibition and facilitation) between the PD patients and the control group was found at the short and the medium ISI (3, 5, 7, 10, 15 and 20 ms) in both hemispheres (P < 0.05). The longer ISI produced non‐significant differences between the two groups in intracortical excitability. There was a non‐significant difference in the motor threshold. In conclusion, it can be supposed that both intracortical inhibition and facilitation are impaired in patients with early PD using other antiparkinsonian treatments than l‐DOPA or dopamine agonists.

Predictive motor timing performance dissociates between early diseases of the cerebellum and Parkinson's disease.

There is evidence that both the basal ganglia and the cerebellum play a role in the neural representation of time in a variety of behaviours, but whether one of them is more important is not yet clear. To address this question in the context of predictive motor timing, we tested patients with various movement disorders implicating these two structures in a motor-timing task. Specifically, we investigated four different groups: (1) patients with early Parkinsons disease (PD); (2) patients with sporadic spinocerebellar ataxia (SCA); (3) patients with familial essential tremor (ET); and (4) matched healthy controls. We used a predictive motor-timing task that involved mediated interception of a moving target, and we assessed the effect of movement type (acceleration, deceleration and constant), speed (slow, medium and fast) and angle (0°, 15° and 30°) on performance (hit, early error and late error). The main results showed that PD group and arm ET subgroup did not significantly differ from the control group. SCA and head ET subjects (severe and mild cerebellar damage, respectively) were significantly worse at interception than the other two groups. Our findings support the idea that the basal ganglia play a less significant role in predictive motor timing than the cerebellum. The fact that SCA and ET subjects seemed to have a fundamental problem with predictive motor timing suggests that the cerebellum plays an essential role in integrating incoming visual information with the motor output in a timely manner, and that ET is a heterogeneous entity that deserves increased attention from clinicians.

Basal ganglia involvement in sensory and cognitive processing. A depth electrode CNV study in human subjects

OBJECTIVE Intracranial recordings were taken from the basal ganglia (BG) in order to explore the possible role of the BG in the cognitive processing of sensory information. METHODS Ten patients with intractable temporal lobe epilepsy, who were candidates for epilepsy surgery, underwent intracranial recordings with depth electrodes. A frontal approach was used for the insertion of diagonal depth electrodes into the amygdalo-hippocampal complex (AH complex). These electrodes passed through the BG. The putamen was explored in 8 patients; the nucleus caudatus and pallidum were explored in two patients. The contingent negative variation (CNV) paradigm was tested using auditory warning stimuli and visual imperative stimuli followed by a hand flexion. The auditory and visual middle and late latency potentials evoked by the warning and imperative stimuli were analyzed. RESULTS (1) Auditory evoked potentials (EPs): the amplitude potential gradient was observed with latencies of (a) 150-195ms (9 patients); (b) 215-290ms (9 patients); and (c) 350-600ms (10 patients). Negative potentials, with latencies of 100 and 110ms were observed in two patients. (2) Visual EPs: (a) 160-195ms (9 patients); (b) 210-295ms (9 patients); and (c) 330-550ms (7 patients). Negative potentials with latencies between 100 and 120ms were observed in 4 patients. CNV was obtained from the BG in 8 patients; a phase reversal was observed twice. CONCLUSIONS (1) The BG generate middle and late latency EPs in a cognitive paradigm linked to the motor task. (2) The BG generate CNV. (3) The BG could play an integrative role in the processing of sensory, cognitive, and motor information.

Efficacy and safety of a standardised 500 unit dose of Dysport® (Clostridium botulinum toxin type A haemaglutinin complex) in a heterogeneous cervical dystonia population: results of a prospective, multicentre, randomised, double-blind, placebo-controlled, parallel group study

Abstract Results from a dose-ranging study in a selected group of de novo patients with rotational cervical dystonia (CD) suggest that 500 units of Dysport (Clostridium botulinum toxin type A haemaglutinin complex) is the optimal starting dose. The present study aimed to confirm the efficacy and safety profile of this dose in a population of CD patients more representative of those seen in a typical dystonia clinic.A total of 68 patients with moderate to severe CD (Tsui score ≥ 9) were randomly assigned to receive placebo or Dysport 500 units. Treatment was administered according to the clinical pattern of head deviation, using a standardised injection protocol. A total of 21 patients (11 Dysport, 10 placebo) had not previously received botulinum toxin type A (BtxA) injections, and 47 patients (24 Dysport, 23 placebo) had received BtxA more than 12 weeks previously. Assessments were performed at baseline and weeks 4, 8 and 16. Patients defined as non-responders at week 4 were re-treated in an open phase with 500 units of Dysport at week 6, and were followed up at week 10.Significant between-group differences in Tsui scores were present at weeks 4 (p=0.001) and 8 (p=0.002). Similarly, there were significant between-group differences (p < 0.001) in patient and investigator assessments of response in favour of Dysport at weeks 4 and 8. Also, more Dysport (49 %) than placebo (33 %) patients were pain-free at week 4 (p=0.02). Overall, 30/35 (86 %) Dysport patients and 14/33 (42 %) placebo patients were classified as responders at week 4. Adverse events were reported by 15/35 Dysport patients and 9/33 placebo patients. Open phase treatment produced improvements in Tsui (p < 0.001) and pain scores (p=0.011), and 23/24 patients were classified as responders.Although individual dose titration and muscle selection is desirable, this study demonstrated that a dose of 500 units of Dysport injected into clinically identified neck muscles without electromyographic guidance is safe and effective in the treatment of patients with the major clinical types of cervical dystonia.

Movement-related potentials in the basal ganglia: a SEEG readiness potential study

OBJECTIVES The brain potentials preceding and accompanying self-paced acral limb movements (Bereitschaftspotential/readiness potential (RP) paradigm) were studied in 12 patients. METHODS Intracranial electrodes were implanted in order to explore intractable epilepsy. The electrodes were introduced into sites corresponding to the electroclinical characteristics of each patients epileptic seizures. In 7 patients, several depth electrodes were implanted orthogonally, in the temporal, fronto-orbital and prefrontal cortex. In 4 patients, subdural strip electrodes were used for the exploration of the fronto-temporal convexity. There were no RPs recorded in these areas. No contacts were placed in the central region known to generate cortical RP. In all the patients, one or two diagonal electrodes passed through or touched the basal ganglia to reach the amygdala and the hippocampus. The putamen was explored in 11 patients (in 3 of them bilaterally); the caudate head was explored in two patients, and the pallidum was explored in two patients. RESULTS RP with a clear amplitude gradient was present in all explored structures, however a phase reversal was never observed. RP was observed in the caudate in all recordings, and in the pallidum in one patient. It was recorded in the putamen in 8 out of the 11 explored patients. RPs were displayed contralaterally to the movement 9 times in 13 explorations, and ipsilaterally 4 times in 9 explorations. The shape of RP resembled the RP shape in the cortex and on the scalp. Movement accompanying potentials (MAPs) were also present in all 3 explored structures. The electrophysiological characteristics of MAP differed from RP, indicating separate generators. In the basal ganglia, RPs preceded the onset of movement by 500-1500 ms, at an average of 1080 (+/-330) ms. It seems that the RP in the basal ganglia starts slightly later than the RP in the motor cortices. That should be definitely demonstrated in patients with simultaneous recordings from cortical and subcortical structures. RP and MAP were displayed synchronously in the cortex and in the basal ganglia during most of the premovement period, as well as during the execution of movement. RP generators were reported by several authors in other deeply located structures, i.e. in the thalamus and in the brain-stem. CONCLUSIONS Based on all these recordings, we presume that the RPs recorded on the scalp are generated simultaneously in several cortical as well as subcortical structures.

A SEEG study of ERP in motor and premotor cortices and in the basal ganglia.

OBJECTIVE Our intention was to study the electrical activity related to the cognitive processing of simple sensory stimuli in the brain structures that participate in motor control. We focused our interest on the 250-600 ms time window, in which cognitive activity most probably provides the basis for the activity recorded. METHODS Intracerebral stereoelectroencephalography (SEEG) recordings were made from 15 epilepsy surgery candidates. We studied potentials that were recorded in a time window in which P300 usually could be recorded on the scalp and that were directly recorded from brain structures involved in motor control: the primary motor cortex (MC, Brodmanns area 4); the lateral and mesial (SMA) premotor cortices (Brodmanns area 6); and the basal ganglia. We evaluated the first distinctive potential to occur in the 250-600 ms time window that displayed an amplitude gradient in several adjacent contacts. Four protocols were performed: an auditory oddball (aP3); a visual oddball (vP3); and contingent negative variation (CNV) protocols, in which the potentials evoked by the auditory warning (aCNV) and visual imperative (vCNV) stimuli were evaluated. In the protocols aP3, vP3, and vCNV, the tested person responded by flexing his/her thumb or hand. In the aCNV paradigm, and in a further auditory oddball paradigm (aP3c), no motor response was required. We compared the presence of an event-related potential (ERP) with an amplitude gradient to the absence of a generator. RESULTS The frequency of P3-like potential components was statistically significantly higher in the basal ganglia when compared with the explored cortical sites. Statistically non-significant latency differences between the basal ganglia and the cortex were displayed. The differences in the distribution of the potentials in the individual cortical areas were insignificant. The mean latency of vP3 was longer than the latencies of aP3, aP3c and vCNV. There was no significant difference between the distribution and latency of aP3 and aP3c. CONCLUSIONS (1) ERPs are generated in cortical as well as in subcortical structures. (2) The cognitive processing of sensory information in all the tested protocols occurred in the basal ganglia; the occurrence in the investigated cortical areas was less frequent and more dependent on the task. The basal ganglia may play an integrative role in cognitive information processing, in motor and non-motor tasks.

Impaired predictive motor timing in patients with cerebellar disorders.

The ability to precisely time events is essential for both perception and action. There is evidence that the cerebellum is important for the neural representation of time in a variety of behaviors including time perception, the tapping of specific time intervals, and eye-blink conditioning. It has been difficult to assess the contribution of the cerebellum to timing during more dynamic motor behavior because the component movements themselves may be abnormal or any motor deficit may be due to an inability to combine the component movements into a complete action rather than timing per se. Here we investigated the performance of subjects with cerebellar disease in predictive motor timing using a task that involved mediated interception of a moving target, and we tested the effect of movement type (acceleration, deceleration, constant), speed (slow, medium, fast), and angle (0°, 15° and 30°) on performance. The subjects with cerebellar damage were significantly worse at interception than healthy controls even when we controlled for basic motor impairments such as response time. Our data suggest that subjects with damage to the cerebellum have a fundamental problem with predictive motor timing and indicate that the cerebellum plays an essential role in integrating incoming visual information with motor output when making predictions about upcoming actions. The findings demonstrate that the cerebellum may have properties that would facilitate the processing or storage of internal models of motor behavior.

The change of prefrontal QEEG theta cordance as a predictor of response to bupropion treatment in patients who had failed to respond to previous antidepressant treatments

UNLABELLED The aim of the study was to examine whether the reduction of theta prefrontal quantitative EEG (QEEG) cordance after one week of bupropion administration is a predictor of response to a 4-week treatment in patients that had failed to respond to previous antidepressant treatments. METHOD EEG data of 18 inpatients were monitored at baseline and after one week. QEEG cordance was computed at 3 frontal electrodes (Fp1, Fp2, Fz). Response to treatment was defined as a >/=50% reduction of MADRS score. RESULTS Nine of the eleven responders and one of the seven non-responders showed decreased prefrontal cordance value after the first week of treatment (p=0.01). Positive and negative predictive values of cordance reduction for the prediction of response to the treatment were 0.9 and 0.75, respectively. CONCLUSION Similar to other antidepressants, the reduction of prefrontal QEEG cordance might be helpful in the prediction of the acute outcome of bupropion treatment.