Deep brain pallidal stimulation for movement disorders in neuroacanthocytosis.
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Acanthocytes↗
Biomedical subjects
P Burbaud
Publications and source records attributed to P Burbaud.
Subthalamic nucleus stimulation in patients with Parkinson's disease does not increase serum ghrelin levels.
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Deep Brain Stimulation↗
Side-effects of subthalamic stimulation in Parkinson's disease: clinical evolution and predictive factors.
Chronic bilateral high-frequency stimulation of the subthalamic nucleus (STN) is an alternative treatment for disabling forms of Parkinson's disease when on-off fluctuations and levodopa-induced dyskinesias compromise patients' quality of life. The aim of this study was to assess the evolution of side-effects during the first year of follow-up and search for clinical predictive factors accounting for their occurrence. We compared the frequency of side-effects at 3 and 12 months after surgery in a cohort of 44 patients. The off-medication scores of Unified Parkinson's Disease Rating Scale (UPDRS) II, III, axial symptoms, disease duration and age at surgery were retained for correlation analysis. Dysarthria/hypophonia, weight gain and postural instability were the most frequent chronic side-effects. Whereas dysarthria/hypophonia remained stable over time, weight gain and postural instability increased during the first year post-op. High axial and UPDRS II scores at surgery were predictive of dysarthria/hypophonia. Age and axial score at surgery were positively correlated with postural instability. Despite the occurrence of side-effects, the benefit/side-effects ratio of STN stimulation was largely positive during the first year of follow-up. Age, intensity of axial symptoms and UDPRS II off-medication score before surgery are predictive factors of dysarthria/hypophonia and postural instability after surgery.
Aged↗
Clinical and economic results of bilateral subthalamic nucleus stimulation in Parkinson's disease.
BACKGROUND: High frequency stimulation of the subthalamic nucleus (STN) is an alternative but expensive neurosurgical treatment for parkinsonian patients with levodopa induced motor complications. OBJECTIVE: To assess the safety, clinical effects, quality of life, and economic cost of STN stimulation. METHODS: We conducted a prospective multicentre study in 95 consecutive Parkinson's disease (PD) patients receiving bilateral STN stimulation and assessed its effects over 12 months. A double blind randomised motor evaluation was carried out at 3 month follow up, and quality of life, self care ability, and predictive factors of outcome following surgery were assessed. The cost of PD was estimated over 6 months before and after surgery. RESULTS: The Unified Parkinson's Disease Rating Scale (UPDRS) motor score improved by 57% (p<0.0001) and activities of daily living improved by 48% (p<0.0001) at 12 month follow up. Double blind motor scoring improved by 51% at 3 month follow up (p<0.0001). The total PD Quality of Life Questionnaire (PDQL-37) score improved by 28% (p<0.001). The better the preoperative motor score after a levodopa challenge, the better the outcome after STN stimulation. Five patients developed an intracerebral haematoma during electrode implantation with permanent after effects in two. The 6 month costs of PD decreased from 10,087 euros before surgery to 1673 euros after surgery (p<0.0001) mainly because of the decrease in medication. These savings allowed a return on the procedure investment, estimated at 36,904 euros over 2.2 years. CONCLUSIONS: STN stimulation has good outcomes with relatively low risk and little cost burden in PD patients with levodopa induced motor complications.
Activities of Daily Living↗
Evolution of postural stability after subthalamic nucleus stimulation in Parkinson's disease: a combined clinical and posturometric study.
OBJECTIVES: The occurrence of postural and balance disorders is a frequent feature in advanced forms of Parkinson's disease (PD). However, the pathological substrate of these disturbances is poorly understood. METHODS: In the present work, we investigated the evolution of posturometric parameters [center of pressure (CoP) displacement and CoP area] and axial scores between the pre-operative period and 3 months post-operative in seven PD patients who underwent bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). RESULTS: After surgery, the patients leaned backwards much more regardless of the STN stimulation, suggesting that surgery could have a deleterious effect on postural adaptation. During the post-operative period, the improvement in axial and postural scores was similar under levodopatherapy and DBS. On the other hand, DBS of the STN significantly reduced the CoP displacement and the CoP area, whereas levodopatherapy tended only to reduce the CoP displacement and to increase the CoP area significantly. CONCLUSIONS: These data suggest that DBS of the STN and levodopa do not act on the same neurological systems involved in posture regulation. DBS of the STN could improve posture via a direct effect on the pedunculopontine nucleus, which is known to be involved in posture regulation.
Adult↗
Time predictability modulates pre-supplementary motor area neuronal activity.
Two monkeys were trained in a delayed sequential motor task in which the time interval between events and the delay duration were either fixed or variable. Single-unit neuronal activity was recorded in the pre-supplementary motor area (pre-SMA). During the delay, we observed a gradual increase in activity (build-up pattern) in the fixed but not in the variable condition. In the former but not in the latter, the monkey had the opportunity to estimate time duration. Consequently, the build-up pattern observed in the pre-SMA might represent the neuronal substrate of a time accumulator system proposed by previous authors on the basis of functional imaging data. Such a system could play a critical role in the working memory of temporal information.
Action Potentials↗
Disruption of information processing in the supplementary motor area of the MPTP-treated monkey: a clue to the pathophysiology of akinesia?
It has been suggested that the underactivity of mesial frontal structures induced by dopamine depletion could constitute one of the main substrates underlying akinesia in Parkinson's disease. Functional imaging and movement-related potential recordings indicate an implication of the frontal lobes in this pathological process, but the question has not yet been investigated at a cellular level using single unit recording. We therefore compared neuronal activity in both the presupplementary motor area (pre-SMA) and the supplementary motor area proper (SMAp) of the Macaca mulatta monkey during a delayed motor task, before and after MPTP treatment. In the pre-SMA, which receives strong inputs from the prefrontal cortex, the baseline firing frequency and the percentage of neurons responding to visual instruction cues decreased in lesioned monkeys. In the SMAp, which sends direct outputs to the primary motor cortex, not only was the response to visual cues impaired, but the percentage of SMAp neurons responding to intracortical microstimulation fell and the threshold of response rose. Neuronal activity after the Go signal diminished sharply in both structures in the symptomatic animal and the discharge pattern became more irregular; in the SMAp neuronal activity remained modified longer. Most of these changes could already be observed in the presymptomatic animal presenting no clinical signs of parkinsonism. These data would indicate that, at the moment when dopamine depletion has impaired the ability of cortical neurons to operate the focused selection of incoming information giving instructions for movement, pre-SMA and SMAp neurons are also in a state of severe hypoactivity. The conjunction of these phenomena could play a critical role in the genesis of akinesia.
Animals↗
Minimal tissue damage after stimulation of the motor thalamus in a case of chorea-acanthocytosis.
Autopsy findings are reported from a patient with chorea-acanthocytosis treated for 2 years by deep brain stimulation (DBS) of the motor thalamus. Postoperative testing showed a progressive improvement in axial truncal spasms. Although relatively high currents were used for 2 years in this patient, postmortem analysis showed minimal tissue damage in the vicinity of the electrode tip. It is concluded that DBS has little impact on the surrounding tissues.
Adult↗
Comparison of neuronal activity in the rostral supplementary and cingulate motor areas during a task with cognitive and motor demands.
A number of cortical motor areas have been identified on the medial wall of the hemisphere in monkeys. However, their specific role in motor control remains unclear. In this study, we sought to describe and compare the functional properties of the presupplementary (pre-SMA) and rostral cingulate (CMAr) motor areas in two monkeys performing a visually instructed, delayed, sequential movement. We recorded 134 task-related neurons in the pre-SMA and 149 in the CMAr. The main difference between the two areas was the abundance of responses to targets (46%) in the pre-SMA, while CMAr activity was more related to reward (28%). Neuronal responses to targets were more phasic and higher in frequency in the pre-SMA than in the CMAr. During the delay, the percentage of neuronal responses was similar in the two areas. The discharge pattern was different depending upon whether the delay duration was fixed or variable but in most neurons was the same regardless of the sequence performed. Movement-related changes were common in the pre-SMA (75%) and in the CMAr (81%) but they occurred earlier in the former. Neurons activated exclusively during movement were more numerous in the CMAr. Finally, neuronal activity in the pre-SMA was more related to the sequential aspect of the task compared to the CMAr. Our results suggest that although the two areas share functional properties, they also participate in different aspects of motor behaviour. Their functional properties reflect their anatomical positions, which give them the potential to integrate external stimuli (pre-SMA) and internal states (CMAr) during motor planning.
Action Potentials↗
Neuronal activity in the monkey motor thalamus during bicuculline-induced dystonia.
Recent data suggest that a decreased basal ganglia output may occur in dystonia, resulting in an increased thalamic drive to the mesial premotor cortex. In a previous work we found that injection of the GABAA antagonist bicuculline into the rostral motor thalamus induced contralateral dystonic postures, whereas myoclonic jerks were frequent after injection into the caudal motor thalamus. In the present study, we performed electrophysiological recordings in the rostral and caudal parts of the ventrolateral thalamus of two cynomolgus monkeys before and after bicuculline injections or saline injections. Discharge frequencies of thalamic neurons were increased after bicuculline injections vs. controls. Their discharge pattern was more bursty in the caudal part in which bursts of neuronal activity were correlated with myoclonic jerks. After bicuculline injection, neurons responded more frequently and less selectively to passive limb movements in both parts of the motor thalamus. Conversely, the response to microstimulation increased after bicuculline injection, particularly in the caudal part. Our data show that acute bicuculline-induced dystonia is associated with a reversible overactivity and disorganization of neuronal activity in the motor thalamus. Such a phenomenon might induce an overspreading of cortical activity leading to dystonia. We postulate that the distinct clinical syndromes observed after bicuculline injections into the rostral and caudal motor thalamus are due to differences both in the neuronal circuitry within each thalamic nucleus and in segregated cortical projections.
Action Potentials↗
Influence of cognitive strategies on the pattern of cortical activation during mental subtraction. A functional imaging study in human subjects.
Functional magnetic resonance imaging (fMRI) at 1.5 T was used to investigate the influence of cognitive strategies on cortical activation during mental calculation. Twenty-nine right-handed subjects performed a serial subtraction of prime numbers. Even though a common corpus of brain areas was activated during this mental calculation, differences appeared between subjects in function of their spontaneous cognitive strategy. In subjects using a so called verbal strategy (n=15), the main activation was located in the whole left dorsolateral frontal cortex with a little activation of the inferior parietal cortex. In subjects using a so called visual strategy (n=14), a bilateral activation in the prefrontal cortex and a high activation in the left inferior parietal cortex were observed. These results demonstrate that numbers are processed through a distributed network of cortical areas, the lateralization of which is clearly influenced by subject strategy.
Adult↗
Bicuculline injections into the rostral and caudal motor thalamus of the monkey induce different types of dystonia.
The pathophysiology of dystonia remains unclear in comparison with other movement disorders. Recent data suggest that there may exist in dystonia an increased thalamic drive to the mesial premotor cortex. To test this hypothesis, we induced overactivity of the motor thalamus by injecting a GABA-A (gamma-aminobutyric acid) antagonist (bicuculline) into the rostral (pallidal) and caudal (cerebellar) ventrolateral nuclei of the thalamus in both hemispheres of one monkey. Dystonic postures were observed in the contralateral limbs and axis. Electromyographic recordings revealed bursts of muscular activation with co-contractions during spontaneous dystonic movements and alterations in muscular patterns during sequential visually guided arm movements. The type of dystonia depended on the site of injections. Rostral thalamic injections induced more severe dystonic postures, whereas myoclonic jerks predominated following caudal injections. We conclude that these two distinct clinical patterns, which are frequently associated in humans, are probably due to a dysfunctioning of segregated thalamic projections to the supplementary motor area (from the rostral part) and to the primary motor cortex (from the caudal part).
Animals↗
A functional magnetic resonance imaging study of mental subtraction in human subjects.
The neuronal network involved in a precise type of calculation procedure, mental subtraction, was investigated by means of functional magnetic resonance imaging. Two tasks were used requiring covert production of numbers: (1) with calculation; (2) without calculation. During the first task, activation was observed in the left dorsolateral prefrontal and premotor cortices, in Broca's area and bilaterally in the inferior parietal cortex. During the second task, activation was mainly observed in Broca's area and to a less extent in the left prefrontal and premotor cortices. Statistical comparison of data in the two situations revealed that the procedure of mental subtraction is mediated by a distributed system which includes predominantly the left dorsolateral prefrontal cortex and the inferior parietal cortex bilaterally.
Adult↗
Reorganization of area 5 neuron activity in trained deafferented monkeys.
A command function is attributable to certain area 5 neurons which clearly fire before movement in trained monkey. Statistical analysis allowed us to define two categories of spontaneous firing mode for these cells: type I which exhibits a random pattern of discharge (14%), and type II displaying markedly "bursty firing". After deafferentation, both categories were still observed in the same proportion. However, the discharge pattern and frequency in type II cells remained altered for 5 months. This paralleled rises in neural latency response (RS) and reaction time (RT). Beginning the 6th month, there was a progressive reorganization of the spontaneous activity along with normalization of RS and RT. Our results support the idea that an enhancement of the excitability of these area 5 neurons, initially depressed by the suppression of sensory inputs, occurs over time. This sensitivity gain could be due to neural network rearrangements induced by repetitive operant solicitation.
Afferent Pathways↗
Stimulus-sensitive spinal segmental myoclonus improved with injections of botulinum toxin type A.
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Adult↗
[Influence of individual strategies on brain activation patterns during cognitive tasks].
Functional magnetic resonance imaging (fMRI) at 1.5 T was used to investigate the influence of cognitive strategies on cortical activation during mental calculation. Twenty-nine right-handed subjects performed a serial subtraction of prime numbers. Data were analyzed taking into account whether the spontaneous strategy of subjects was verbal (n = 15) or visual (n = 14). Even thought a common corpus of brain areas was activated during this mental calculation task, i.e. the dorsolateral prefrontal, premotor and parietal cortices, and Broca's area, differences appeared between the two groups of subjects. In subjects using a verbal strategy, the main activation was located in the whole left dorsolateral frontal cortex with a little activation of the inferior parietal cortices. In subjects using a visual strategy, a bilateral activation in the prefrontal cortex and a high activation in the left inferior parietal cortex were observed. These results demonstrate that numbers are processed through a distributed network of cortical areas, the lateralization of which is clearly influenced by subject strategy. Taken together this data reveals a functional interaction between the left inferior parietal cortex and the right prefrontal cortex in the visuo-spatial sketchpad for number processing. This network could be involved in sustained selective attention to mental numerical images generated in the left inferior parietal cortex.
Adult↗
Cellular distribution of adenosine A2A receptor mRNA in the primate striatum.
The cellular expression of adenosine A2A receptor mRNA in the adult monkey and human striatum was examined by using single and double in situ hybridization with ribonucleotide probes. Analysis on adjacent sections demonstrated a homogeneous overlapping expression of adenosine A2A receptor and preproenkephalin A mRNAs throughout nucleus caudatus, putamen, and nucleus accumbens. By contrast, high expression of preproenkephalin A mRNA but no expression of adenosine A2A receptor mRNA was found in the nucleus basalis of Meynert. Double in situ hybridization demonstrated an extensive colocalization of adenosine A2A receptor and preproenkephalin A mRNAs in approximately 50% of the medium-sized spiny neurons of the monkey nucleus caudatus, putamen, and nucleus accumbens. A small number of neurons (4-12%) that contained adenosine A2A receptor mRNA but not preproenkephalin A mRNA was found along the ventral borders of the striatum. Virtually all adenosine A2A receptor mRNA-containing neurons co-expressed dopamine D2 receptor mRNA, whereas only very few adenosine A2A receptor mRNA containing neurons co-expressed dopamine D1 receptor or substance P mRNAs. In addition, a sub-population of adenosine A2A receptor mRNA-expressing neurons that also contained preproenkephalin A mRNA was found in the septum in monkeys. These results demonstrate that there is a high expression of adenosine A2A receptor mRNA in the primate striatum that is extensively co-localized with dopamine D2 receptor and preproenkephalin A mRNAs. It is concluded that adenosine A2A receptors are likely to be important for the parallel organization of primate striatal neurotransmission and that these receptors could be a target for drug therapy in Parkinson's disease.
Animals↗
Movement disorders induced by gamma-aminobutyric agonist and antagonist injections into the internal globus pallidus and substantia nigra pars reticulata of the monkey.
Injections of bicuculline into the medial segment of the globus pallidus (GPi) of the monkey induced dose-dependent hypokinesia with dystonic attitudes in contralateral limbs whereas muscimol injections elicited choreiform movements. Injections of the same drugs in substantia nigra pars reticulata (SNr) provoked severe axial postural anomalies with rotational behavior. Conversely, contralateral hypertonia after bicuculline and contralateral hypotonia after muscimol injections were observed. These data suggest that GABA inputs into GPi and SNr play different roles in terms of motor and postural control and add new insights into the pathophysiology of dystonias.
Animals↗