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PubMed2005

The first evaluation of brain shift during functional neurosurgery by deformation field analysis.

Stereotactic surgery is based on a high degree of accuracy in defining and localising intracranial targets and placing surgical tools. Brain shift can influence its accuracy significantly. Deep brain stimulation of the subthalamic nucleus can markedly change the quality of life of patients with advanced Parkinson's disease, but the outcome depends on the quality of electrode placement. A patient is reported in whom the placement of the second electrode was not successful. Deformation field analysis of pre- and postoperative three dimensional magnetic resonance images showed an intraoperative brain movement of 2 mm in the region of the subthalamic nucleus (the target point). Electrode repositioning resulted in efficient stimulation effects. This case report shows the need to reduce risk factors for intraoperative brain movement and demonstrates the ability of deformation field analysis to quantify this complication.

Aged↗
PubMed2006

Neuronal activity of the zona incerta in Parkinson's disease patients.

The objective of this study was to describe the firing characteristics of the zona incerta (ZI) in Parkinson's disease patients. The ZI constitutes a band of gray matter lying dorsal to the subthalamic nucleus, whose firing properties have not been well defined in humans yet. ZI proved to become hyperactive in 6-OHDA-lesioned rats as compared to normal rats, and regarding these noticeable changes in the discharge patterns it was suggested that ZI could be a putative target for the surgical treatment of Parkinson's disease. Twelve patients who underwent microrecording-guided subthalamic surgery consented to the study. Neurons from different tracts were classified as belonging to the ZI according to their firing features, background extracellular activity, anatomical mapping of trajectories, and atlas confirmation. Fifty-nine neurons were classified as belonging to ZI. The mean firing rate proved to be 29.5 Hz, with a broad dispersion band, even covering subthalamic nucleus (STN) frequency ranges. Pattern analysis showed heterogeneous neuronal signals ranging from tonic to burst and paused neurons. A decrease in extracellular background activity in the defined ZI was also observed. Five of the recorded neurons showed rhythmical spike trains with oscillations of 8 to 14 Hz, and two units were found to discharge trains at 4 Hz. None of the recorded ZI neurons responded to proprioceptive maneuvers. ZI presented firing activities with a broad spectrum in terms of frequency and tonicity. It is differentiated from STN recordings in Parkinson's disease patients mainly because of absent proprioceptive-related units and diminished extracellular background activity.

Aged↗
PubMed2001

Organization of inputs from cingulate motor areas to basal ganglia in macaque monkey.

The cingulate motor areas reside within regions lining the cingulate sulcus and are divided into rostral and caudal parts. Recent studies suggest that the rostral and caudal cingulate motor areas participate in distinct aspects of motor function: the former plays a role in higher-order cognitive control of movements, whereas the latter is more directly involved in their execution. Here, we investigated the organization of cingulate motor areas inputs to the basal ganglia in the macaque monkey. Identified forelimb representations of the rostral and caudal cingulate motor areas were injected with different anterograde tracers and the distribution patterns of labelled terminals were analysed in the striatum and the subthalamic nucleus. Corticostriatal inputs from the rostral and caudal cingulate motor areas were located within the rostral striatum, with the highest density in the striatal cell bridges and the ventrolateral portions of the putamen, respectively. There was no substantial overlap between these input zones. Similarly, a certain segregation of input zones from the rostral and caudal cingulate motor areas occurred along the mediolateral axis of the subthalamic nucleus. It has also been revealed that corticostriatal and corticosubthalamic input zones from the rostral cingulate motor area considerably overlapped those from the presupplementary motor area, while the input zones from the caudal cingulate motor area displayed a large overlap with those from the primary motor cortex. The present results indicate that a parallel design underlies motor information processing in the cortico-basal ganglia loop derived from the rostral and caudal cingulate motor areas.

Action Potentials↗
PubMed1985

Efferent connections of the ventral pallidum: evidence of a dual striato pallidofugal pathway.

Previous histological and histochemical studies have provided evidence that the globus pallidus (external pallidal segment) as conventionally delineated in the rat extends ventrally and rostrally beneath the transverse limb of the anterior commissure, invading the olfactory tubercle with its most ventral ramifications. This infracommissural subdivision of the globus pallidus or ventral pallidum (VP) is most selectively identified by being pervaded by a dense plexus of substance-P-positive striatofugal fibers; the extent of this plexus indicates that the VP behind the anterior commissure continues dorsally over some distance into the anteroventromedial part of the generally recognized (supracommissural) globus pallidus; the adjoining anterodorsolateral pallidal region, here named dorsal pallidum (DP), receives only few substance-P-positive fibers, but contains a dense plexus of enkephalin-positive striatal afferents that also pervades VP. Available autoradiographic data indicate that VP and DP receive their striatal innervation from two different subdivisions of the striatum: whereas VP is innervated by a large, anteroventromedial striatal region receiving substantial inputs from a variety of limbic and limbic-system-associated structures (and therefore called "limbic striatum"), DP receives its striatal input from an anterodorsolateral striatal sector receiving only sparse limbic afferents ("nonlimbic" striatum) but instead heavily innervated by the sensorimotor cortex. The present autoradiographic study has produced evidence that this dichotomy in the striatopallidal projection is to a large extent continued beyond the globus pallidus: whereas the efferents of DP were traced to the subthalamic nucleus and substantia nigra, those of VP were found to involve not only the subthalamic nucleus and substantia nigra but also the frontocingulate (and adjoining medial sensorimotor) cortex, the amygdala, lateral habenular and mediodorsal thalamic nucleus, hypothalamus, ventral tegmental area, and tegmental regions farther caudal and dorsal in the midbrain. These findings indicate that the ventral pallidum can convey striatopallidal outflow of limbic antecedents not only into extrapyramidal circuits but also back into the circuitry of the limbic system.

Acetylcholinesterase↗
PubMed2002

Presynaptic parkinsonism in multiple system atrophy mimicking Parkinson's disease: a clinicopathological case study.

We describe the clinicopathological findings in a patient aged 63 years at death who, at age 55 years, developed levodopa-responsive parkinsonism with no atypical features. A diagnosis of idiopathic Parkinson's disease (PD) was made. During the clinical course, fluctuations and dyskinesias appeared. Eight years after onset, he was successfully treated with subthalamic nucleus stimulation but died 3 weeks postoperatively from pulmonary embolus. Brain autopsy showed marked neuronal loss and gliosis in the substantia nigra and locus coeruleus, and, to a much lesser extent, in the basis pontis, inferior olivary nuclei, and cerebellar cortex. Striatum was normal. There were numerous oligodendroglial and neuronal cytoplasmic inclusions and neuropil threads, the highest density being localized in the pons and cerebellar white matter. No Lewy bodies were observed. We conclude that nigral, presynaptic parkinsonism may occur in multiple system atrophy, which even in the long run can be indistinguishable from PD. Putaminal preservation accounts for good response to both levodopa therapy and subthalamic nucleus stimulation.

Brain↗
PubMed2001

Deep brain stimulator electrodes used for lesioning: proof of principle.

OBJECTIVE: Patients with chronically implanted deep brain stimulator (DBS) electrodes can encounter complications requiring hardware removal. We assessed the safety and efficacy of using implanted DBS electrodes to create a therapeutic lesion before their removal. METHODS: Revision or removal of the DBS electrodes was required in two patients who had previously undergone DBS implantation. We conducted a series of in vitro experiments to confirm that the DBS electrodes could be used to generate radiofrequency lesions and to assess the relationship between radiofrequency parameters and lesion size. With this information, and with the approval of the hospital ethical review board, implanted electrodes were used to create incremental radiofrequency lesions in the thalamus in one patient and in the subthalamic nucleus in another. The procedures were performed under local anesthesia with contiguous contacts of the DBS lead connected to the active and reference sites of the RF generator to create a bipolar lesion. RESULTS: A 51-year-old man with essential tremor and a thalamic DBS required repeated battery changes secondary to tolerance and high voltage demands. Rather than replacing the battery, a radiofrequency thalamotomy was performed by using the existing left DBS electrode. At the 6-month follow-up examination, successful lesioning provided near complete tremor control. A second patient, a 50-year-old man with Parkinson's disease who had undergone bilateral subthalamic deep brain stimulation, developed skin erosion over the DBS hardware. A subthalamic nucleus lesion was made through the right DBS electrode. Lesion position and size were confirmed with magnetic resonance imaging. CONCLUSION: Lesions can be made through chronically implanted DBS electrodes in a safe, graded fashion and can produce therapeutic benefit.

Device Removal↗
PubMed1999

Extrastriatal dopaminergic innervation of human basal ganglia.

A tyrosine-hydroxylase immunohistochemical analysis of the brains of normal human individuals has revealed nigrostriatal axons providing collaterals that arborize in the pallidum and subthalamic nucleus. These thin and varicose collaterals emerge from thick and smooth axons that course backward along the main output pathways of the basal ganglia, including the ansa lenticularis, the lenticular fasciculus and Wilson's pencils. Many of these fibers run within pallidal medullary laminae before reaching the putamen, whereas others climb along the reticular thalamic nucleus to reach the caudate nucleus. This extrastriatal innervation, which allows nigral dopaminergic neurons to directly affect the pallidum and subthalamic nucleus, may play a crucial role in the functional organization of human basal ganglia, in both health and disease.

Adult↗
PubMed2003

Different methods for anatomical targeting.

AIM: Several procedures are used in the different neurosurgical centers in order to perform stereotactic surgery for movement disorders. At the moment no procedure can really be considered superior to the other. We contribute with our experience of targeting method. METHODS: Ten patients were selected, in accordance to the guidelines for the treatment of Parkinson disease, and operated by several methods including pallidotomy, bilateral insertion of chronic deep brain electrodes within the internal pallidum and in the subthalamic nucleus (18 procedures). INTERVENTIONS: in each patient an MR scan was performed the day before surgery. Scans were performed axially parallel to the intercommissural line. The operating day a contrast CT scan was performed under stereotactic conditions. MEASURES: after digitalization of the MRI images, it was possible to visualize the surgical target and to relate it to parenchimal and vascular anatomic structures readable at the CT examination. The CT scan obtained was confronted with the MR previously performed, the geometrical relation between the different parenchimal and vascular structures and the selected targets were obtained. Stereotactic coordinates were obtained on the CT examination. RESULTS: It was possible to calculate the position of the subthalamic nucleus and of the internal pallidum on the CT scan, not only relating to the intercommissural line, but considering also the neurovascular structures displayed both on the MRI and the CT scans. CONCLUSION: The technique that our group presents consist in an integration between information derived from the CT and the MR techniques, so that we can benefit from the advantages of both methods and overcome the disadvantages.

Aged↗
PubMed2006

Neuropsychological effects of bilateral STN stimulation in Parkinson disease: a controlled study.

OBJECTIVE: To evaluate the cognitive and behavioral effects of bilateral subthalamic nucleus (STN) stimulation in patients with Parkinson disease (PD). METHODS: The authors included 103 patients; 99 patients were evaluated 6 months after surgery. A control group of 39 patients with PD was formed and 36 patients were evaluated 6 months later. At baseline and at follow-up we administered neuropsychological tests of language, memory, visuospatial function, mental speed, and executive functions. A depression rating scale, a quality of life scale, self and proxy ratings of memory and dysexecutive symptoms, and a neuropsychiatric interview were also administered. RESULTS: Six months after surgery, the STN group showed a larger decline than the control group on measures of verbal fluency, color naming, selective attention, and verbal memory. Moreover, the STN group showed a decrease in positive affect, and an increase in emotional lability and cognitive complaints. On the other hand, the STN group showed an increase in quality of life and a slight decrease in depressive symptoms. Nine percent of the STN patients had psychiatric complications (vs 3% of controls). CONCLUSIONS: Bilateral subthalamic nucleus stimulation has an adverse effect on executive functions with implications for daily life of the patients and their relatives.

Cognition Disorders↗
PubMed2000

The indirect basal ganglia pathway in dopamine D(2) receptor-deficient mice.

Recent pathophysiological models of basal ganglia function in Parkinson's disease predict that specific neurochemical changes in the indirect pathway would follow the lack of stimulation of D(2) dopamine receptors. Post mortem studies of the basal ganglia in genetically modified mice lacking functional copies of the D(2) dopamine receptor gene allowed us to test these predictions. When compared with their congenic N(5) wild-type siblings, mice lacking D(2) receptors show an increased expression of enkephalin messenger RNA in the striatum, and an increased activity and expression of cytochrome oxidase I in the subthalamic nucleus, as expected. In addition, D(2) receptor-deficient mice display a reduced expression of glutamate decarboxylase-67 messenger RNA in the globus pallidus, as the basal ganglia model predicts. This reduction contrasts with the lack of change or increase in glutamate decarboxylase-67 messenger RNA expression found in animals depleted of dopamine after lesions of the mesostriatal dopaminergic system. Furthermore, D(2) receptor-deficient mice show a significant decrease in substance P messenger RNA expression in the striatonigral neurons which form the direct pathway. Finally, glutamate decarboxylase-67 messenger RNA expression in the basal ganglia output nuclei was not affected by mutations in the D(2) receptor gene, a fact that could probably be related to the absence of a parkinsonian locomotor phenotype in D(2) receptor-deficient mice. In summary, these findings provide compelling evidence demonstrating that the lack of endogenous stimulation of D(2) receptors is sufficient to produce subthalamic nucleus hyperactivity, as assessed by cytochrome oxidase I histochemistry and messenger RNA expression, and strongly suggest the existence of interactions between the basal ganglia direct and indirect pathways.

Animals↗
PubMed1999

Mechanism and consequences of nerve cell death in Parkinson's disease.

The etiology of Parkinson's disease remains unknown, making it difficult to develop therapeutical approaches to stop the progression of the disease. The best known treatment to date is based on the use of L-DOPA or dopaminergic agonists. These are merely substitutive therapies and have limitations because of their side effects. Thus, the development of new therapeutical strategies will require a far better knowledge of the mechanism and the consequences of nerve cell death in Parkinson's disease. Parkinson's disease is characterized by a selective vulnerability of sub-populations of dopaminergic neurons in the mesencephalon. The fact that the neurons which degenerate in Parkinson's disease are already sensitive to oxidative stress in control subjects and the reported increased production of oxygen free radicals in Parkinson's disease suggest that oxidative stress may be involved in the mechanism of nerve cell death. Furthermore, oxygen free radicals are also involved in an oxygen-dependent pro-apoptotic pathway stimulated by the inflammatory reaction observed in Parkinson's disease. These data suggest that anti-oxidant or anti-inflammatory treatments may slow down the progression of the disease. On the other hand, new substitutive therapies may be developed by trying to restore the activity of the neurons located downstream from the nigrostriatal pathway. Indeed, the nigrostriatal denervation induces a hyper-activity of the output structures of the basal ganglia (internal segment of the globus pallidus and substantia nigra pars reticulata), as demonstrated in various animal models of the disease. These changes in the activity of the output structures of the basal ganglia seem to be directly induced by the hyperactivity of the glutamatergic afferent fibers from the subthalamic nucleus. The fact that L-DOPA treatment or a reduction in the activity of the subthalamic nucleus alleviate the symptoms of the disease and restore the activity of the output structures of the basal ganglia in parkinsonism suggests that these structures play a key role in the pathophysiology of the disease and could represent a potential therapeutic target.

Animals↗
PubMed1996

Corticobasal degeneration: widespread argentophilic threads and glia in addition to neurofibrillary tangles. Similarities of cytoskeletal abnormalities in corticobasal degeneration and progressive supranuclear palsy.

A 57-year-old man had exhibited cortical sensory disturbance, rigidity, spasticity, dementia, alien hand, grasp reflex, supranuclear ophthalmoplegia, pseudobulbar palsy, and neck dystonia for 4 years. Histological examination of autopsied specimens revealed neuronal loss in the cerebral cortex, with ballooned neurons, subthalamic nucleus, substantia nigra, basal ganglia, midbrain tegmentum, and the thalamus. There were neurofibrillary tangles in the subthalamic nucleus and the substantia nigra. Gallyas-Braak silver impregnation demonstrated numerous argentophilic tangles, threads, and a few argentophilic glia in the cerebral cortex, subcortical white matter, particularly in the precentral gyrus, subcortical nuclei, and the brainstem. These argentophilic structures were largely positive for tau, and negative for ubiquitin, paired helical filaments, and phosphorylated neurofilament. Ultrastructurally, 15-nm-wide straight tubules were observed in the neurons of the substantia nigra, globus pallidus, and the precentral cortex, coexisting with a few twisted tubules periodically constricted at 160- to 230-nm intervals. It was conclusively shown that Gallyas- and tau-positive cytoskeletal abnormalities occurred widely in brain of corticobasal degeneration. Both distribution and morphology of abnormal phosphorylated tau protein in corticobasal degeneration appear to resemble these features in progressive supranuclear palsy. These findings suggest a common cytoskeletal etiopathological significance in corticobasal degeneration and progressive supranuclear palsy.

Basal Ganglia↗
PubMed1983

Glutamate uptake, glutamate decarboxylase and choline acetyltransferase in subcortical areas after sensorimotor cortical ablations in the cat.

High affinity glutamate uptake (HAGU), glutamate decarboxylase (GAD) and choline acetyltransferase (CAT) activities were measured from subcortical nuclei in the cat brain after ipsilateral ablation of the sensorimotor cortex. Results showed a drop in HAGU in all the structures assayed except the subthalamic nucleus. These changes in HAGU are generally accompanied by a decrease in GAD while CAT is unaffected. However, in the red nucleus the drop in HAGU is concomitant to an increase in GAD and CAT. In the subthalamic nucleus HAGU and CAT are increased while GAD is decreased. These results are consistent with the concept that most corticofugal fibres to subcortical structures use glutamate as their neurotransmitter. Results concerning GAD suggest that GABAergic subcortical neurons are under a cortical influence. This influence seems to be weak on cholinergic neurons.

Animals↗
PubMed2001

Assessments of axial motor control during deep brain stimulation in parkinsonian patients.

OBJECTIVE: We tested the hypothesis that bilateral deep brain stimulation (DBS) in the globus pallidus internus or the subthalamic nucleus improves various components of postural and oromotor function and that some of the components correlate with changes in the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's disease. METHODS: Six patients with Parkinson's disease were evaluated for four postural and two orofacial UPDRS items, and quantitative tests of posture adjustments and oromotor control were performed while the patients were on and off DBS. Measurements of postural adjustments included reactive force and latency before a voluntary step. The oromotor assessments involved velocity and amplitude changes during voluntary jaw movement. RESULTS: DBS significantly improved the total UPDRS motor score by an average of 44%, which included improvement of 18 to 54% in the postural and orofacial items. DBS also decreased foot lift-off latency significantly, but it produced a variable response to the preparatory postural force in the swing limb. DBS significantly improved jaw-opening velocity by 14 to 50% and jaw opening amplitude by 5 to 41%. Significant correlations for the percentage change from off and on DBS occurred among a few UPDRS items and foot lift-off latency and jaw-opening velocities. CONCLUSION: DBS in either the globus pallidus internus or the subthalamic nucleus induces improvements in bradykinesia of specific components of postural and oromotor control, which also can be measured by the postural and orofacial UPDRS items. In some Parkinson's disease patients, DBS results in improvements in force or amplitude control, although these changes are not reflected in changes in UPDRS postural and orofacial items. A battery of quantitative and clinical tests must be used to evaluate the effects of DBS on axial motor control adequately.

Electric Stimulation↗
PubMed1982

Projections of the pedunculopontine tegmental nucleus in the rat: evidence for additional extrapyramidal circuitry.

The projections of the pedunculopontine tegmental nucleus (PPT) were studied in the rat using anterograde and retrograde transport methods. Ascending fibers to the substantia nigra, the subthalamic nucleus, the globus pallidus, the entopeduncular nucleus, the neostriatum, the ventral thalamus, and the medial and sulcal frontal cortical areas were identified. PPT has been reported to receive afferents from the substantia nigra, the subthalamic nucleus, the entopeduncular nucleus and the neostriatum. The connections of PPT provide an additional limb to extrapyramidal circuitry.

Afferent Pathways↗
PubMed1993

The organization of the descending ventral pallidal projections in the monkey.

This study describes the organization and topography of the descending efferent projections from the monkey ventral pallidum. The main efferent projections from the globus pallidus are to the subthalamus, to the thalamus, and to the substantia nigra. Although these projections have been well established for the dorsal pallidum, the projections of the ventral pallidum have not been explored in primates. The results of this study add an important link in how information from the limbic lobe is channeled through the basal ganglia in monkeys. Anterograde tracers, Phaseolus vulgaris-leucoagglutinin, and tritiated amino acids were injected into various regions of the ventral pallidum. The descending efferent projection from the ventral pallidum in monkeys terminates primarily in the subthalamic nucleus and adjacent lateral hypothalamus, in the substantia nigra, and in the lateral habenular nucleus. Although terminals are also found in the thalamus, these are relatively sparse. The projections to the subthalamic nucleus and the lateral hypothalamus are topographically arranged, while those to the substantia nigra are not. These results suggest that pathways from distinct pallidal regions that receive specific striatal input terminate in distinct regions of the subthalamic/hypothalamic regions, thus maintaining a topographic arrangement. Projections to the substantia nigra, however, overlap extensively, suggesting convergence of terminals from different ventral pallidal regions. The relatively small projection to the thalamus raises the question that without a prominent thalamic projection, is this system parallel to that described for the dorsal globus pallidus?

Amino Acids↗
PubMed1978

[Connections between the globus pallidus and putamen and the hypothalamus and subthalamus].

In 16 adult cats with electrolytically destructed external and internal parts of the globus pallidus and in 8 cats with destructed putamen direct strio-pallido-hypothalamic and strio-pallido-subthalamic pathways have been studied. Degeneration of the axonal preterminals and terminals have been examined in preparations treated after Nauta--Gygax, Nauta--Laidlow, Finck--Heimer with simultaneous additional staining of the nuclei with cresyl violet after Kawamura--Niimi. Direct pallido- and putamen-hypothalamic pathways to nuclei of the grey tubercle, posterior and lateral nuclei of the hypothalamus were stated. Direct pathways from the putamen to the subthalamic nucleus have been revealed, however, these pathways are represented in less degree than those of pallido-subthalamic connections. Direct pathways from the external portion of the globus pallidus and putamen to the subthalamic nucleus are more pronounced and represented by greater numbers of projections than those of strio-pallido-hypothalamic origin.

Animals↗
PubMed2003

Gait and Balance Dysfunction in Adults.

Determining the precise cause of gait dysfunction in adults is often difficult because of the multifactorial nature of the disorder. Additionally, elderly patients have other comorbidities that further complicate their diagnosis. A proper history and physical examination, however, often allow the clinician to arrive at the correct diagnosis. Once a diagnosis is reached, appropriate therapeutic decisions can be made. Patients presenting with Parkinsonism need a thorough evaluation to rule out potentially reversible conditions, such as normal pressure hydrocephalus. Patients with idiopathic Parkinson's disease usually develop gait difficulty and freezing episodes late in the course of the illness. Another important cause of gait disturbance in adults is the cerebellar ataxias. Among the sporadic forms, gluten sensitivity is an important consideration. Identification of this entity is important, because the disease process can be halted with a gluten-free diet. Another group is the paraneoplastic ataxias, which can often be diagnosed in the proper clinical setting. Most of the adult-onset hereditary ataxias are autosomal dominant conditions. Except for the episodic ataxias, treatment of these conditions has been disappointing. Mixed results have been obtained with the use of amantadine, buspirone, and 5-hydroxytryptophan. Physical therapy plays an important role in the gait rehabilitation of these patients. Over the past several years, researchers have developed a greater understanding of motor control and how it relates to freezing. Clinicians can now train patients to use external cues to overcome their motor blocks. Another important advance has been the development of subthalamic nucleus deep brain stimulation in the treatment of patients with troublesome peak dose dyskinesia and other motor fluctuations. Subthalamic nucleus deep brain stimulation should be considered when best medical treatment fails. Cortical myoclonus can be treated with levetiracetam, which has US Food and Drug Administration approval as an antiepileptic agent. It has been quite effective in the treatment of myoclonus and should be considered when other medications fail.

Journal Article↗