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, Brodmann's area 4); the lateral and mesial (SMA) premotor cortices (Brodmann's 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.

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.

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 > or = 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.

Amantadine infusion in treatment of motor fluctuations and dyskinesias in Parkinson's disease.

Efficiency and safety of amantadine sulfate (AMS) infusions were investigated in late stage complications of Parkinson's disease (PD). In an open-label study, 21 PD patients suffering from motor fluctuations and/or dyskinesias were administered AMS infusions (PK-Merz, 400 mg per day) during seven days. Oral AMS treatment followed. Significant improvement of UPDRS motor scores was observed between day 0 and day 7, remaining improved until day 21. Based on patients' diary notes, both severity and occurrence of hypokinetic "off" state significantly decreased (from 6.6 to 3.1 hours, p < 0.001, average "off" time per day) as well as dopaminergic-induced dyskinesias (from 2.5 to 1.3 hours, p < 0.05, average duration of dyskinesias per day). AMS infusions followed by oral administration appeared as a safe method for improvement of both motor fluctuations and dyskinesias in advanced PD. In advantage to simple oral therapy, AMS infusions allowed fast introduction of a profound and durable treatment effect.

Lateralization of the P22/N30 precentral cortical component of the median nerve somatosensory evoked potentials is different in patients with a tonic or tremulous form of cervical dystonia.

Somatosensory evoked potentials (SEPs) of the median nerve were recorded in 40 patients with the tonic and tremulous form of torticollis and in 40 healthy volunteers. Polymyographic recordings of the activity of cervical muscles were performed in all patients with cervical dystonia to determine the dystonic and antagonistic muscles. Patient SEPs were recorded during abnormal head movement. SEPs in 20 healthy volunteers were recorded with the head in the middle position. SEPs in another 20 healthy volunteers were recorded with the head rotated 60 degrees to the right. The mean peak-to-peak amplitude values of the precentral P22/N30 and the postcentral N20/P25 complexes and their mean side-to-side ratios were calculated in the F3 (F4), C3' (C4'), and C3+ (C4+) electrode positions in all four groups. In patients with the tonic form of torticollis (group I), an apparent mean P22/N30 amplitude increase was found above the hemisphere contralateral to the direction of head deviation in both precentral electrode positions, F3(4) and C3(4)'. A statistically significant difference was observed between group I and other patient and control groups. In patients with the tremulous form of torticollis (group II), an increase in the mean P22/N30 amplitude was found above both hemispheres in both precentral electrode positions F3(4) and C3(4)'; a significant difference was found between group II and both control groups. Lateralization of the P22/N30 component was found only in patients with the tonic form of torticollis. The mean side-to-side ratio of the precentral P22/N30 component amplitude was significantly different when group I was compared with either group II or control groups. No significant difference between group II and either control group was found. No significant abnormalities in the postcentral N20/P25 component were found in either the dystonic patients or in healthy control subjects. These results might indicate a different pattern of cortex excitability in patients with tonic versus tremulous forms of torticollis and therefore may implicate different underlying pathophysiological mechanisms in these two forms of disorder.

Change in lateralization of the P22/N30 cortical component of median nerve somatosensory evoked potentials in patients with cervical dystonia after successful treatment with botulinum toxin A.

The precentral P22/N30 cortical component of the median nerve somatosensory evoked potentials (SEPs) was recorded in 16 patients (11 women and five men) suffering from cervical dystonia before and after botulinum toxin therapy. Cervical dystonia was diagnosed as idiopathic in all patients: 13 patients suffered from right-sided torticollis, and three suffered from left-sided torticollis. The amplitude of the P22/N30 component and the side-to-side ratio of amplitude values were measured. Normal values were obtained by acquiring measurements in two groups of healthy volunteers (n1 = 20 and n2 = 20). The recordings in the first control group were done with the patient's head in a normal position, whereas, in the second control group, the patient kept the head intentionally rotated 60 degrees to the right. Patients were treated with local injections of botulinum toxin A (BTX-A). The mean duration of treatment was 8.3 months, and the mean total amount of BTX injected was 295 U. The P22/N30 precentral component was repeatedly recorded in patients after head posture had been corrected to the normal plane by BTX-A treatment. The recordings showed that the amplitude of the P22/N30 precentral component recorded contralaterally to the direction of head deviation was significantly higher in patients before treatment than after treatment. Contralateral pretreatment amplitudes were also significantly higher (p < 0.01 and p < 0.05, respectively) than amplitudes in both groups of healthy volunteers. The mean side-to-side ratio of precentral P22/N30 component amplitudes was significantly higher in patients before treatment compared with after treatment and also compared with both control groups. These changes in dystonic patients probably reflect the direction of head rotation, the muscle pattern of torticollis, and the change in force of dystonic contraction after the treatment. The changes presumably could be the result of higher excitability of the precentral cortex contralateral to head rotation in patients with cervical dystonia and its change after successful BTX-A treatment.

Lateralization of the P22/N30 component of somatosensory evoked potentials of the median nerve in patients with cervical dystonia.

Somatosensory evoked potentials (SEPs) of the median nerve were recorded in 40 patients suffering from cervical dystonia and in 40 healthy volunteers as a control. Before recording the median nerve SEPs, polymyographic recordings were performed in all patients with cervical dystonia. The activity of cervical muscles was recorded, and the leading muscle of cervical dystonia was determined. Patients were divided into two groups according to the results of polymyography. The leading muscle was sternocleidomastoid in the first group and the splenius capitis in the second group. Patient SEPs were recorded during abnormal head rotation. SEPs in 20 healthy volunteers were recorded with the head in the middle position. SEPs of another 20 healthy volunteers were recorded with the head rotated 60 degrees to the right. The mean peak-to-peak amplitude values of the precentral P22/N30 complex and the mean ratio of the P22/N30 amplitudes between both hemispheres were calculated in the F3 (F4) and C3' (C4') electrode positions in all four groups. No significant lateralization of the precentral P22/ N30 component was found in either group of healthy volunteers. In dystonic patients in whom the sternocleidomastoid was determined as the leading muscle of dystonia, a statistically significant lateralization of the P22/N30 component toward the ipsilateral side of the leading muscle was found. In the group with the splenius capitis determined as the leading muscle of dystonia, a statistically significant lateralization of the P22/N30 component toward the contralateral side of the leading muscle was found. The possibility that the precentral cortex is activated differently in cervical dystonia patients who have different muscle patterns of dystonia is discussed.