Hana Streitová

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.

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.

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.

Cognitive potentials in the basal ganglia—frontocortical circuits. An intracerebral recording study

We studied cognitive functions related to processing sensory and motor activities in the basal ganglia (BG), specifically in the putamen and in cortical structures forming the BG-frontocortical circuits. Intracerebral recordings were made from 160 brain sites in 32 epilepsy surgery candidates. We studied P3-like potentials in five different tests evoked by auditory and visual stimuli, and two sustained potentials that are related to cognitive activities linked with movement preparation: BP (Bereitschaftspotential) and CNV (contingent negative variation). We compared the presence of a potential with a phase reversal or an amplitude gradient to the absence of a generator. All of the studied cognitive potentials were generated in the BG; the occurrence in frontal cortical areas was more selective. The frequency of all but one potential was significantly higher in the BG than in the prefrontal and in the cingulate cortices. The P3-like potentials elicited in the oddball paradigm were also more frequent in the BG than in the motor/premotor cortex, while the occurrence of potentials elicited in motor tasks (BP, CNV, and P3-like potentials in the CNV paradigm) in the motor cortex did not significantly differ from the occurrence in the BG. The processing of motor tasks fits with the model by Alexander et al. of segregated information processing in the motor loop. A variable and task-dependent internal organisation is more probable in cognitive sensory information processing. Cognitive potentials were recorded from all over the putamen. The BG may play an integrative role in cognitive information processing.

The impact of motor activity on intracerebral ERPs: P3 latency variability in modified auditory odd-ball paradigms involving a motor task

The P3 wave of event-related potentials was recorded with intracranial electrodes in 24 epileptic patients during the pre-surgical evaluation of epilepsy surgery. Three different cognitive auditory paradigms were used: (1) odd-ball paradigm with no output required (PGI) where patients had simply to recognize target tones, (2) odd-ball with motor response (PGII), where patients had to press a button in response to target tones, and (3) odd-ball with both counting task and motor response (PGIII), where patients had to recognize target tones, press a button in response to them, and count their number. The occurrence of P3 potential, its latency and amplitude, and the dependence of P3 latency on the task complexity were calculated. Identifiable P3 potentials in all the three paradigms were recorded from locations in mesial cortex (18 locations mesial temporal, eight locations mesial frontal, two locations mesial parietal) and lateral sites (eight sites lateral temporal, five lateral frontal, and two lateral parietal). P3 latency values ranged from 257 to 320 ms in all explored cortical areas when PGI was used; they significantly increased or decreased during PGII and PGIII, depending on the task and structure explored. In the mesial temporal cortex, the changes of P3 latency between paradigms were minimal. In the mesial parietal cortex, there was significant P3 delay in both PGII and PGIII relative to PGI. In the mesial frontal cortex, there was a significant latency decrease in PGII, and practically identical mean latency in PGI and PGIII. In all lateral cortices (temporal, frontal and parietal), there was always a P3 latency increase in PGII and PGIII relative to PGI, the most significant results being observed in the parietal and frontal lateral areas. The results support the multi-generator theory of P3. Prolongation of the mean P3 latency in lateral frontal and parietal cortices when the paradigm involved the execution of a motor task might reflect specific gating in this area during active movements, while the absence of modification in the temporal lobe may reflect minimal involvement of this region in motor planning or processing. The prolongation of mean P3 latency in practically all lateral structures in PGIII suggests that most cortical areas were involved in the cognitive functions needed for this test. The finding of reduction and subsequent prolongation of P3 latency in the mesial frontal cortex might reflect the unique specialization of this area and its specific involvement in motor processing.