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Biomedical subjects

J Guridi

Publications and source records attributed to J Guridi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Deep brain stimulation of the globus pallidus pars interna in advanced Parkinson's disease.

Pallidotomy is now widely performed for the treatment of advanced Parkinson's disease (PD). Preliminary reports of the effect of globus pallidus pars interna deep brain stimulation (GPi DBS) have also been promising. We have analyzed a cohort of 22 consecutive patients enrolled in a multicenter study. Surgery was bilateral in 17 and unilateral in five patients. At 6-month follow-up, the bilaterally GPi-implanted patients demonstrated a marked improvement when examined after drug withdrawal ("off") and under optimal medication ("on") using the Unified Parkinson's Disease Rating Scale (UPDRS). The benefit induced by the stimulation in the "off" medication condition in the total motor score was 31% and in the activities of daily living (ADL) scores was 39%. During the "on" medication period, the reduction in the total "on" dyskinesias score was 66% and in the ADL score was 32%. A similar pattern of improvement was seen in the group of patients with unilateral GPi stimulation, although a second cohort of 12 patients not included in the multicenter study showed greater improvements in "on" motor functioning. Although the effect of DBS is predominantly reversible, electrode insertion alone resulted in measurable clinical effects in the absence of stimulation. Thus, at 6-month follow-up, the benefit observed without stimulation was up to 44% in the "on" dyskinesias score and 29% in timed tapping scores undertaken in the "off" medication state. Complications among 34 patients from all centers included perioperative infection (n=3), hardware fracture (n=2), and premature battery failure (n=3). These results show a positive antiparkinsonian effect of pallidal DBS. No specific complications were observed with bilateral procedures.

Adult↗
PubMed2000

Bilateral deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is rapidly becoming the preferred surgical choice for the treatment of advanced Parkinson's disease (PD). We report initial results in 15 patients after 12 months and in nine patients evaluated between 30 and 36 months postoperatively. Our experience confirms the robust antiparkinsonian effect of DBS of the STN in advanced PD. The severity of "off" episodes, as assessed by the Unified Parkinson Disease Rating Scale (UPDRS), was drastically reduced by 74% at 12 months, and dyskinesia scores (Dyskinesia Rating Scale) decreased. The levodopa daily dose was reduced by 55% at 12 months. A double-blind assessment to determine the effect of stimulation performed in nine patients at 3 months in the "off" medication condition was very significant (p<0.05). Nine patients have been followed for 3 years with maintained efficacy in the UPDRS "off" score and the dyskinesia score. The experience of other groups using a similar technique is reviewed. The overall assessment indicates a high antiparkinsonian effect of DBS of the STN even in advanced patients. The existence of a learning curve for this procedure should be taken into account when initial results are evaluated.

Electric Stimulation Therapy↗
PubMed2000

Pathophysiologic basis of surgery for Parkinson's disease.

Dopamine depletion induces a series of changes in the basal ganglia motor circuit that underlie the origin of the cardinal features of Parkinson's disease. It has now been established that hyperactivity of the subthalamic nucleus (STN) is an essential feature of the parkinsonian state. This leads to increased excitatory driving onto the globus pallidum internum (GPi) and substantia nigra reticulata (SNr) which, in turn, overinhibits the motor projections to the thalamus and brainstem. The STN and GPi have become the preferred targets for surgery to treat PD. In keeping with the classic pathophysiologic model, physiologic and neuroimaging studies in patients have shown that lesioning or functional blockades (by deep brain stimulation, or DBS) of these nuclei increased cortical activation, in parallel with clinical improvements of bradykinesia. Neuronal recording during surgery has also shown tremor-related activity in both the STN and GPi. However, the pathophysiologic model of the basal ganglia needs further refinement to provide a more detailed explanation of the origin of both tremor and rigidity in Parkinson's disease and to explain the antidyskinetic effect of surgery of the GPi and STN.

Basal Ganglia↗
PubMed1999

Stereotactic targeting of the globus pallidus internus in Parkinson's disease: imaging versus electrophysiological mapping.

OBJECTIVE: The reintroduction of pallidotomy for the treatment of Parkinson's disease (PD) has generated various opinions regarding the ideal anatomic or physiological location of the target within the globus pallidus. The role of microelectrode recording guidance in pallidotomy for the treatment of advanced PD is presently under debate. The purpose of this study was twofold. The first goal was to determine the degree of accuracy in the targeting of the globus pallidus internus (GPi) with magnetic resonance imaging (MRI), by comparing these results with the final placement of the thermolytic lesions (as defined by electrophysiological assessment). The second goal was to ascertain the somatotopic arrangement of the GPi in PD. METHODS: The analysis involved 50 patients with PD who underwent microrecording-guided pallidotomy. The theoretical coordinates for lesioning were calculated after definition of the intercommissural line by MRI. The actual placement of the lesions was determined after mapping of the GPi by microrecording, using stimulation to identify the sensorimotor region and its somatotopic organization. RESULTS: In most cases, the lesions were placed posterior and lateral to the targets chosen by MRI. Mapping by microrecording revealed differences of 2.3 +/- 1.55 mm and 3 +/- 1.9 mm in the mediolateral and anteroposterior coordinates, respectively. The actual lesion overlapped the theoretical target for only 45% of the patients. The somatotopic organization of the GPi was analyzed. Most of the units with sensorimotor activity or tremor-related activity were in the lateral portion of the nucleus. Upper limb and axial units were in the most lateral region and mainly in the ventral one-third of the nucleus. Lower limb responses were recorded mainly in the dorsal one-third of the nucleus. Tremor-related cells were found throughout the sensorimotor region of the nucleus. CONCLUSION: These results indicate that lesion targeting based on MRI alone is not sufficiently accurate to guarantee placement of the lesion in the sensorimotor region of the GPi.

Adult↗
PubMed1999

[Pallidotomy in the treatment of complicated Parkinson's disease: clinical results at two years and analysis of prognostic factors].

BACKGROUND: There is a renewed interest in pallidotomy as a treatment for complicated Parkinson's disease (PD). AIM: To present the clinical results as well as the analysis of prognostic factors obtained in 28 patients with PD and motor complications submitted to pallidotomy and followed by one year (n = 28) and 2 years (n = 12). RESULTS: The total motor score (Unified Parkinson's Disease Rating Scale [UPDRS]) in the off state improved by 33 and 23% at one and two years, respectively (p < 0.01). All the cardinal signs of the disease were significantly improved (p < 0.01): tremor (92%), rigidity (67%), bradykinesia (46%) and axial symptoms (21%). A slight tendency to worsening in axial symptoms was observed. Dyskinesias disappeared in all but one patient. The Schawb & England Scale in off was improved by 21%. No improvement in the non-operated side was observed. The subgroup of patients with an improvement of less than 30% in the UPDRS was older than the one with larger clinical benefit. The observed tendency to worsening in the total motor score was related mainly to the progression of the symptoms in the non-operated side. Complications were mild and transient. CONCLUSIONS: Pallidotomy is a relatively safe and effective therapeutic option for complicated PD patients. An adequate selection of patients is necessary, since efficacy is partial and limited to one hemibody.

Adult↗
PubMed1999

[Pathophysiological bases, clinical results and indications for surgical treatment in Parkinson disease].

We review the present status of surgery for Parkinson's disease. Surgical options for Parkinson's disease are rapidly spanding. The main objectives of surgical techniques are to restore the dopaminergic deficit in the striatum (transplantation) and to normalize the neuronal activity of the subthalamic-pallidal circuit (pallidotomy and deep brain stimulation). Whereas cell transplantation is still considered an experimental procedure, ablative procedures and deep brain stimulation are widely used. Both types of surgical procedures are supported by strong scientific data. However, much work remains to be done in order to understand several aspects not clearly elucidated at present. The results and current indications for pallidotomy and deep brain stimulation are analyzed.

Brain↗
PubMed1997

A brief history of pallidotomy.

A large number of surgical procedures involving the globus pallidus and ansa lenticularis were performed from 1939 to the late 1950s for alleviation of rigidity and tremor, two of the main symptoms of Parkinson's disease. Several groups reported beneficial effects using a wide array of techniques and targets within the pallidum and its projections. Over time, pallidal targets lying in the ventral and posterior portions of the internal pallidum were considered to be the most effective. Based on anatomic studies, surgical misadventures, and empirical observations, there was an abrupt shift regarding the favored target to treat parkinsonian tremor to the thalamus, and most neurosurgeons abandoned pallidotomy in the 1960s. With the advent of L-dopa and the realization of its striking clinical benefits in the mid 1960s, within 5 to 10 years, virtually all surgery for Parkinson's disease ceased. We are now witnessing a rediscovery of pallidotomy as patients with Parkinson's disease are experiencing the shortcomings of medical therapy. In this article, we examine the evolution of pallidotomy and discuss the reasons for the renewed interest in this procedure.

Animals↗
PubMed1997

Surgical treatment of Parkinson's disease.

At present, there are three major surgical approaches to Parkinson's disease (PD): (1) Ablative surgery (i.e. pallidotomy, thalamotomy); (2) deep brain stimulation (DBS) of the thalamus, internal globus pallidus (GPi) and subthalamic nucleus (STN); and (3) grafting fetal mesencephalic cells into the striatum. As a result of increasing understanding of the pathophysiology of the basal ganglia and the demonstration of surgical alleviation of experimental parkinsonism, surgery has regained a paramount importance in the management of PD. The aim of pallidotomy and DBS is to reduce the excessive inhibitory output from the GPi and substantia nigra reticulata (SNr). Pallidotomy and DBS of the STN or GPi aim to reverse the pathophysiological consequences of dopamine deficiency in PD, and should be considered entirely symptomatic treatments. The ideal candidates for pallidotomy are young patients in good general health in whom dyskinesias are the main reasons for disability. Patients with severe bilateral problems uncontrollable with present pharmacological tools are candidates for DBS. As yet, there are no formal data to help decide how to choose between GPi and STN stimulation. In our practice, patients are allocated to GPi stimulation when 'on' dyskinesias are extremely severe. In most other instances, we prefer to perform STN stimulation. At present there is almost no reason to decide for the thalamic stimulation since tremor is equally arrested by STN stimulation, which in addition improves all other features of PD. Equally the only indication for thalamotomy would be a patient with long-standing tremor as the main clinical manifestation, which can not be controlled with drugs. The proportion of patients in whom the thalamus will be the preferable target for either DBS or thalamotomy is small (less than 5%). Grafting aims to repair the nigrostriatal pathway and restore dopaminergic function in the striatum. In the future implants containing not only dopaminergic cells but also growth factors and a variety of other substances could become a method to not only functionally compensate the biochemical abnormalities of PD but also to arrest its progression. This technique is limited to a few centres around the world owing to the technical, logistical and ethical problems of obtaining and handling embryonic cells. At present, grafting of dopaminergic cells is perhaps best suited for patients with young-onset PD (less than 45 years old) who are at high risk of developing complications within a short time of beginning pharmacological treatment and in whom the idea of making lesions or implanting electrodes into the brain for decades seems less appealing. Consideration of surgery in any given patient should be weighed against the risks (about 1% mortality and 2-6% of severe morbidity-hemiplegia, cognitive deficit, speech problems, etc.) associated with these techniques. The development of better imaging methods and the growing expertise of multidisciplinary teams will undoubtedly make surgery for PD safer and more effective in the future.

Electric Stimulation Therapy↗
PubMed1997

[Stereotactic surgery in Parkinson's disease].

Stereotactic surgery for Parkinson's disease (PD) has regained interest due to the recently described hyperactivity of the subthalamic-pallidal pathway. Many patients suffering from complications associated with the chronic use of levodopa may benefit from surgical treatments. There are different surgical targets and techniques (ablative and deep brain stimulation). The choice of one particular target and technique relies on the clinical symptoms of the patient. The risk/benefit ratio of surgery is related to the careful selection of patients and the technical accuracy. Intraoperative microrecording is considered the best method to avoid side effects and partial results. A series of patient's selection and follow-up assessment criteria are proposed.

Follow-Up Studies↗
PubMed1996

Subthalamotomy in parkinsonian monkeys. Behavioural and biochemical analysis.

Nineteen Macaca fascicularis monkeys were divided into four different groups: Group A (n = 3), control; Group B (n = 3), monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Group C (n = 8), animals treated with MPTP in which the subthalamic nucleus (STN) was unilaterally lesioned by kainic acid injection; in Group D (n = 5), the STN was lesioned prior to MPTP administration. Subthalamotomy resulted in a bilateral improvement of tremor, spontaneous activity, bradykinesia (evaluated by a manual motor test) and freezing in Group C. All these monkeys developed hemichorea contralateral to the lesion. The improvement was maintained and the hemichorea continued until death. The monkeys in group D showed severe hemiballism which persisted throughout MPTP administration and developed parkinsonian signs mainly on the side ipsilateral to the lesion. Analysis of the in situ hybridization of the mRNA coding for glutamic acid decarboxylase (GAD) of MPTP monkeys showed a significant increase in the mean density of silver grains over every labelled neuron in the globus pallidum lateralis (56.8% over control) as well as the globus pallidus medialis (GPM) (45.7% over control) and the substantia nigra reticulata (SNR) (35.8% over control). No significant change was observed in the thalamic nucleus reticularis. Subthalamotomy (Groups C and D) produced a significant reduction in mRNA GAD expression on the side of the lesion in the GPM and the SNR (34% and 42.3%, respectively) with respect to the ipsilateral (non-lesioned) side and also when compared with parkinsonian monkeys. These results confirm and expand, at the cellular level, the paramount role of STN hyperactivity in the pathophysiology of parkinsonism. The therapeutic consequences of these findings for surgical treatment of Parkinson's disease are discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

Consequences of nigrostriatal denervation on the gamma-aminobutyric acidic neurons of substantia nigra pars reticulata and superior colliculus in parkinsonian syndromes.

To examine the effects of nigrostriatal denervation on the substantia nigra pars reticulata (SNpr), one of the main outputs of the basal ganglia, we used quantitative in situ hybridization to analyze the messenger RNA coding for Mr 67,000 glutamic acid decarboxylase (GAD67 mRNA) in the SNpr neurons from patients with Parkinson's disease (PD), monkeys rendered parkinsonian by 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP), and their respective controls. In MPTP-intoxicated monkeys, the expression of GAD67 mRNA was increased in the SNpr neurons, and the increase was reversed by L-dopa treatment. There were no differences in the level of GAD67 mRNA between PD patients who had been treated with L-dopa and control subjects. Combined with the previously reported increased expression of GAD67 mRNA in the internal segment of the pallidum of MPTP-intoxicated monkeys, these data suggest that the gamma-aminobutyric acid (GABAergic) activity of the output system of the basal ganglia is globally increased by nigrostriatal denervation. We also analyzed the level of GAD67 mRNA expression in the superior colliculus, a structure that receives the inhibitory influence of the GABAergic neurons of the SNpr and that is involved in eye movement control. GAD67 mRNA expression was reduced in both MPTP-intoxicated monkeys, whether or not they received L-dopa therapy, and PD patients, compared to their respective controls. This decrease may result from the hyperactivity of the inhibitory nigrotectal pathway, but also from other influences since it was not corrected by L-dopa therapy. These changes may account for the slight ocular motor and visuospatial cognitive impairment occurring in PD, even after L-dopa therapy.

Animals↗
PubMed1996

Consequence of nigrostriatal denervation and L-dopa therapy on the expression of glutamic acid decarboxylase messenger RNA in the pallidum.

To examine the consequences of nigrostriatal denervation and L-dopa treatment on the basal ganglia output system, we analyzed, by quantitative in situ hybridization, the messenger RNA coding for glutamic acid decarboxylase (Mr 67,000) (GAD67 mRNA) in pallidal cells from patients with Parkinson's disease (PD), monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) receiving or not receiving L-dopa, and their respective control subjects. In MPTP-treated monkeys, the expression of GAD67 mRNA was increased in cells from the internal pallidum, and this effect was abolished by L-dopa treatment. There were no differences in the levels of GAD67 mRNA between patients with PD, who were all treated with L-dopa, and control subjects. These results indicate that the level of GAD67 mRNA is increased in the cells of the internal pallidum after nigrostriatal dopaminergic denervation and that this increase can be reversed by L-dopa therapy.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Effects of nigrostriatal denervation and L-dopa therapy on the GABAergic neurons in the striatum in MPTP-treated monkeys and Parkinson's disease: an in situ hybridization study of GAD67 mRNA.

The effects of nigrostriatal denervation and L-dopa therapy on GABAergic neurons were analysed in patients with Parkinson's disease and in monkeys rendered parkinsonian by MPTP intoxication. The expression of the messenger RNA coding for the 67 kDa isoform of glutamic acid decarboxylase (GAD67 mRNA), studied by quantitative in situ hybridization, was used as an index of the GABAergic activity of the striatal neurons. A significant increase in GAD67 mRNA expression, generalized to all GABAergic neurons, was observed in MPTP-treated monkeys compared to control monkeys in the putamen and caudate nucleus (+44 and +67% respectively), but not in the ventral striatum. L-Dopa therapy significantly reduced GAD67 mRNA expression in the putamen and caudate nucleus to levels similar to those found in control monkeys. However, the return to normal of GAD67 mRNA expression was not homogeneous across all neurons since it was followed by an increase of labelling in one subpopulation of GABAergic neurons and a decrease in another. These data suggest that in MPTP-treated monkeys the degeneration of nigrostriatal dopaminergic neurons results in a generalized increase in GABAergic activity in all the GABAergic neurons of the striatum, which is partially reversed by L-dopa therapy. As the expression of GAD67 mRNA is less intense in the ventral than in the dorsal striatum, this increase in striatal GABAergic activity may be related to the severity of nigrostriatal denervation. In parkinsonian patients who had been chronically treated with L-dopa, GAD67 mRNA expression was significantly decreased in all GABAergic neurons, in the caudate nucleus (by 44%), putamen (by 43.5%) and ventral striatum (by 26%). The opposite variation of GAD67 mRNA in patients with Parkinson's disease, compared with MPTP-treated monkeys, might be explained by the combination of chronic nigrostriatal denervation and long-term L-dopa therapy.

Aged↗
PubMed1994

Subthalamotomy improves MPTP-induced parkinsonism in monkeys.

Hyperactivity of the subthalamic nucleus (STN) is major characteristic of parkinsonism secondary to substantia nigra lesions. Interruption of the STN-internal pallidum (GPi) pathway is a new stereotactic target for Parkinson's disease. We have studied the antiparkinsonian efficacy of STN lesions in MPTP-treated monkeys. Four rhesus monkeys were made parkinsonian by MPTP (i.v. 0.15 +/- 1 mg/kg) administration over 3 months. Unilateral subthalamotomy (kainic acid) was performed by a standard stereotactic method. Severity was rated from 0 (normal) to V by fine manual motor tests. Three monkeys (severity state III/IV) showed marked improvement in spontaneous activity, facial expression and manual dexterity bilaterally but significantly greater in the limb contralateral to the lesion. Mild hemichorea was present in 2 and hemiballism in one. L-Dopa treatment (50 mg b.i.d.) enhanced the hemidyskinesias moderately. The therapeutic effect has persisted for over 8 months postsurgery. Monkey No.4 (severity stage V) showed chorea in the lower limb contralateral to the lesion but no improvement and died a few days later. Subthalamotomy improves parkinsonism in moderately severe parkinsonian monkeys. Dyskinesia might be a persistent complication.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗