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Thalamotomy versus thalamic stimulation for multiple sclerosis tremor.

Disabling intractable tremor occurs frequently in patients with multiple sclerosis (MS). There is currently no effective medical treatment available, and the results of surgical intervention have been variable. Thalamotomy has been the mainstay of neurosurgical therapy for intractable MS tremor, however the popularisation of deep brain stimulation (DBS) has led to the adoption of chronic thalamic stimulation in an attempt to ameliorate this condition. With the goal of examining the relative efficacy and adverse effects of these two surgical strategies, we studied twenty carefully selected patients with intractable MS tremor. Thalamotomy was performed in 10 patients, with chronic DBS administered to the remaining 10. Both thalamotomy and thalamic stimulation produced improvements in postural and intention tremor. The mean improvement in postural tremor at 16.2 months following surgery was 78%, compared with a 64% improvement after thalamic stimulation (14.6 month follow-up) (P > 0.05). Intention tremor improved by 72% in the group undergoing thalamotomy, a significantly larger gain than the 36% tremor reduction following DBS (P < 0.05). Early postoperative complications were common in both groups. Permanent complications related to surgery occurred in four patients overall. Following thalamotomy, long-term adverse effects were observed in three patients (30%), and comprised hemiparesis and seizures. Only one patient in the thalamic stimulation group experienced a permanent deficit (monoparesis). We conclude that thalamotomy is a more efficacious surgical treatment for intractable MS tremor, however the higher incidence of persistent neurological deficits in patients receiving lesional surgery may support the use of DBS as the preferred surgical strategy.

Adult↗

Subthalamic nucleus stimulation affects a frontotemporal network: a PET study.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective strategy in the treatment of motor symptoms in advanced Parkinson's disease. However, clinical studies have shown that DBS can affect verbal fluency. Seven Parkinson's disease patients with bilateral DBS of the STN were studied with positron emission tomography (PET) to investigate the effects of STN stimulation on regional cerebral blood flow during a verbal fluency task. Activation of the right orbitofrontal cortex and verbal fluency-associated activation within a left-sided frontotemporal network were decreased during STN stimulation compared with the OFF state. Our results offer an explanation for the commonest neuropsychological side effect of STN stimulation and show that STN stimulation affects a frontotemporal network during a fluency task.

Aged↗

Chronic precentral stimulation in trigeminal neuropathic pain.

The results of Deep Brain Stimulation in deafferentation pain syndromes, in particular in thalamic pain, indicate that excellent long-term pain relief can hardly ever be achieved. We report 7 cases using Motor-Cortex-Stimulation for treating severe trigeminal neuropathic pain syndromes, i.e., dysaesthesia, anaesthesia dolorosa and postherpetic neuralgia. The first implantation of the stimulation device for precentral cerebral stimulation was performed in June 1993, the last in September 1995. In all but one case the impulse-generator was implanted after a successful period of test stimulation. Successful means a pain reduction of more than 50% as assessed with a Visual Analogue Scale. Excluding one case, in whom a prolonged focal seizure resulting in a postictal speech arrest occurred during test stimulation, there have been no operative complications and the postoperative course was uneventful. In all the other patients the pain inhibition appeared below the threshold for producing motor effects. Initially these patients reported a good to excellent pain relief. In three of 6 patients a good to excellent pain control was maintained for a follow-up period of 5 months to 2 years. In the remaining three patients the positive effect decreased over several months.

Adult↗

Neuronal electrical high frequency stimulation modulates presynaptic GABAergic physiology.

Electrical high frequency deep brain stimulation (DBS) of the globus pallidus internus (GPi) or the subthalamic nucleus (STN) has dramatic beneficial motor effects in advanced Parkinson's disease (PD). However, the mechanisms underlying these clinical results remain unclear. It is proposed that the gamma-aminobutyric acid (GABA) system is involved in the effectiveness of DBS. To prove this hypothesis, rat striatal slices were stimulated electrically (130 Hz) in vitro; GABA and glutamate (GLU) outflow from striatal slices of normal or kainic acid-lesioned rats were measured after o-phthaldialdehyde sulphite derivatization using HPLC with electrochemical detection. Our results could demonstrate that high frequency stimulation (HFS) did not modulate basal GABA outflow in the perfusate. In the presence of submaximal concentrations of the voltage-gated sodium channel opener veratridine, HFS significantly enhanced GABA outflow. When the GABA transporter inhibitor, nipecotic acid, was added to the incubation medium, the HFS effects decreased to nearly control values. Destruction of striatal GABAergic neurons by kainic acid completely reversed the effects of HFS on GABA outflow. In the present study no effect of HFS on glutamate outflow was observed under any condition. These results suggest that HFS has a specific effect on GABAergic neuronal terminals resulting in an enhancement of extracellular GABA in the caudate nucleus. This effect is probably due to an inhibitory effect of HFS on the GABA uptake system rather than to stimulation of vesicular GABA release from GABAergic neurons, which are both associated with the presynaptic GABAergic physiology.

Animals↗

Studying neurosurgical implants for Parkinson disease: a question of design.

North American researchers' perspectives on designing neurosurgical implant studies for Parkinson disease (PD) challenged the custom of holding surgical trials to less stringent evidentiary standards than other clinical studies. Researchers supported placebo surgery-controlled trials. The framework they used to design and evaluate studies both of deep brain stimulation and cellular implants for PD may be applicable to a broad range of surgical implants for other disorders.

Biomedical Research↗

Stimulation of the nervous system for the management of seizures: current and future developments.

Vagal nerve stimulation (VNS) for the treatment of refractory epilepsy appears to have started from the theory that since VNS can alter the EEG, it may influence epilepsy. It proved effective in several models of epilepsy and was then tried in short-term, open-label and double-blind trials, leading to approval in Canada, Europe and the US. Follow-up observations in these patients demonstrated continued improvement in seizure control for up to 2 years. Close to 50% of treated patients have achieved at least a 50% reduction in seizure frequency. This therapy was also useful as rescue therapy for ongoing seizures in some patients; many patients are more alert. The initial trials were completed in patients >/=12 years of age with refractory partial seizures. Subsequently, similar benefits were shown in patients with tuberous sclerosis complex, Lennox-Gastaut syndrome, hypothalamic hamartomas and primary generalised seizures. Implanting the generator and leads is technically easy, and complications are few. The method of action is largely unknown, although VNS appears to alter metabolic activity in specific brain nuclei. Considering that improvement in mood is frequently found in patients using VNS, it has undergone trials in patients with depression. Other illnesses deserving exploration with this unusual therapy are Alzheimer's disease and autism. Some aspects of VNS have proven disappointing. Although patients have fewer seizures, the number of antiepileptic drugs they take is not significantly reduced. In addition, there is no way to accurately predict the end of life of the generator. Optimal stimulation parameters, if they exist, are unknown. Deep brain stimulation is a new method for controlling medically refractory seizures. It is based on the observation that thalamic stimulation can influence the EEG over a wide area. Several thalamic nuclei have been the object of stimulation in different groups of patients. Intraoperative brain imaging is essential for electrode placement. The procedure is done under local anaesthesia. Experience with this therapy is currently limited, but growing.

Brain↗

Acute and separate modulation of motor and cognitive performance in parkinsonian rats by bilateral stimulation of the subthalamic nucleus.

The subthalamic nucleus (STN) is involved in motor and cognitive performance through its key role in the basal ganglia-thalamocortical circuits, but how these different modalities (motor and cognition) are controlled (similar vs. dissimilar) has not yet been elucidated. In the present study, the effects of bilateral STN deep brain stimulation (DBS) on motor and cognitive performance were investigated in a rat model of Parkinson disease (PD). After being trained in a choice reaction time (CRT) task, rats received bilateral injections of 6-hydroxydopamine (6-OHDA) into the striatum. One group of 6-OHDA animals was implanted bilaterally with stimulation electrodes at the level of the STN. Stimulations were performed at 130 Hz (frequency), 60 micros (pulse width), and varying amplitudes of 1, 3, 30, and 150 microA during the CRT task. Finally, rats were sacrificed and the brains processed for staining to determine the dopaminergic lesion (TH immunohistochemistry) and localization of the electrode tip (HE histochemistry). Bilateral 6-OHDA infusion significantly decreased (70%) the number of dopaminergic cells in the substantia nigra pars compacta (SNc) and increased motor time (MT), proportion of premature responding (PR), and reaction time (RT). Bilateral STN stimulation with an amplitude of 3 microA normalized 6-OHDA-induced deficits in PR and RT. Simulation with an amplitude of 30 microA reversed the lesion-induced deficits in MT and RT. Our data show for the first time that bilateral STN stimulation differentially affected the 6-OHDA-induced motor and cognitive deficits. This means that basal ganglia-thalamocortical motor and associative circuits responsible for specific motor and cognitive performance, which are processed through the STN, have unique physiological properties that can acutely and separately be modulated by specific electrical stimuli.

Animals↗

Neural repair strategies for Parkinson's disease: insights from primate models.

Nonhuman primate models of Parkinson's disease (PD) have been invaluable to our understanding of the human disease and in the advancement of novel therapies for its treatment. In this review, we attempt to give a brief overview of the animal models of PD currently used, with a more comprehensive focus on the advantages and disadvantages presented by their use in the nonhuman primate. In particular, discussion addresses the 6-hydroxydopamine (6-OHDA), 1-methyl-1,2,3,6-tetrahydopyridine (MPTP), rotenone, paraquat, and maneb parkinsonian models. Additionally, the role of primate PD models in the development of novel therapies, such as trophic factor delivery, grafting, and deep brain stimulation, are described. Finally, the contribution of primate PD models to our understanding of the etiology and pathology of human PD is discussed.

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

[Subthalamic stimulation in a patient with multiple system atrophy: a clinicopathological report].

INTRODUCTION: Efficacy of high frequency subthalamic nucleus (STN) stimulation has been demonstrated in idiopathic Parkinson's disease (IPD). However, since it may be difficult to differentiate IPD from multiple system atrophy with parkinsonian presentation (MSA-P), a few cases of MSA-P has been treated by deep brain stimulation (DBS) and showed no sustained improvement of clinical signs. We report a patient with a clinical misdiagnosed MSA-P, later confirmed by neuropathological study, who was improved by DBS for one year. CASE REPORT: A 63-year-old parkinsonian patient had been treated by levodopa for 6 years with a persistent good response. Over one year he progressively developed disabling fluctuations with severe axial syndrome and vegetative non motor symptoms in off periods. After checking usual contraindications, he was included in surgical procedure protocol (bilateral STN stimulation). During the first year after surgery, the clinical status improved with disappearance of non motor fluctuations, a 45 percent decrease of the OFF UPDRS III score, and a 39 percent reduction of the treatment. However after one year, axial symptoms reappeared with recurrent falls, as well as increasing dysarthry and swallowing difficulties which were only slightly improved by levodopa. He developed severe urinary disorders increased by a prostatic adenoma which led to surgical treatment. During the post operative period, 2 years after DBS, he died suddenly from an unexplained cause. A cerebral autopsy was performed and showed a good position of the two electrodes in the STN. Microscopic studies revealed severe neuronal depletion in the substantia nigra but no Lewy bodies. Immunohistochemical methods demonstrated numerous argyrophilic glial cytoplasmic inclusions positive for alpha-synuclein and ubiquitin in the STN, putamen, globus pallidus, pontine nuclei and cerebellar white matter, significant of MSA. CONCLUSION: This case shows that DBS can improve parkinsonian signs in MSA-P with persistent dopa sensitivity. However, probably because of striatal degeneration progression, this improvement is time limited and STN DBS cannot be recommended in MSA.

Adenoma↗

Surgical insights into Parkinson's disease.

Surgery for Parkinson's disease was popularized in the mid-twentieth century before the advent of effective medical therapies. Early lesioning treatments contributed to our understanding of the functional anatomy of Parkinson's disease. Observations of the limitations and long-term complications of established pharmacological therapies for Parkinson's disease, together with major contributions from animal research to elucidate the roles of the basal ganglia in movement disorders, inspired a recent renaissance in neurosurgical interventions for Parkinson's disease including deep brain stimulation; this continues to yield much neurophysiological information. The development of potentially restorative treatment modalities, such as gene therapy, neural transplantation and nanotechnology, hold much promise for surgery, both therapeutically and in revealing further insights into Parkinson's disease pathophysiology.

Catheter Ablation↗

Stimulation of the subthalamic region facilitates the selection and inhibition of motor responses in Parkinson's disease.

The aim of the present study was to specify the involvement of the basal ganglia in motor response selection and response inhibition. Two samples were studied. The first sample consisted of patients diagnosed with Parkinson's disease (PD) who received deep-brain stimulation (DBS) of the subthalamic nucleus (STN). The second sample consisted of patients who received DBS for the treatment of PD or essential tremor (ET) in the ventral intermediate nucleus of the thalamus (Vim). Stop-signal task and go/no-go task performances were studied in both groups. Both groups performed these tasks with (on stimulation) and without (off stimulation) DBS to address the question of whether stimulation is effective in improving choice reaction time (RT) and stop-signal RT. The results show that DBS of the STN was associated with significantly enhanced inhibitory control, as indicated by shorter stop-signal RTs. An additional finding is that DBS of the STN led to significantly shorter choice RT. The effects of DBS on responding and response inhibition were functionally independent. Although DBS of the Vim did not systematically affect task performance in patients with ET, a subgroup of Vim-stimulated PD patients showed enhanced stop-signal RTs in on stimulation versus off stimulation. This result suggests that the change in performance to stop signals may not be directly related to STN function, but rather results from a change in PD function due to DBS in general. The findings are discussed in terms of current functional and neurobiological models that relate basal ganglia function to the selection and inhibition of motor responses.

Adult↗

Extradural motor cortex stimulation in advanced Parkinson's disease: the Turin experience: technical case report.

OBJECTIVE AND IMPORTANCE: At our institution, extradural motor cortex stimulation (EMCS) has recently been applied for treating Parkinson's disease symptoms. We report our results and review the literature supporting this application of EMCS. CLINICAL PRESENTATION: Since 1998, six patients affected by advanced Parkinson's disease and not fulfilling inclusion criteria for deep brain stimulation underwent EMCS. INTERVENTION: A quadripolar electrode was introduced in the extradural space over the motor cortex, opposite to the side on which parkinsonian symptoms had begun. Bipolar chronic electrostimulation was delivered at 2.5 to 6 V, 150 to 180 microseconds, and 25 to 40 Hz. Preoperative and postoperative clinical status was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and recorded on videotapes. The follow-up of this series varied from 4 months to 2.5 years. After EMCS, the overall UPDRS score decreased by 42 to 62%; Section III UPDRS score (motility evaluation) by 32 to 83%; and Section IV UPDRS score (therapy complications) by 100% in two patients, by 50 to 67% in four patients, and by 33% in one patient. L-Dopa therapy was reduced by 11 to 33% in three patients and by 70 to 73% in the other two patients. No postoperative complications or negative side effects of electrostimulation were recorded, except for a misplacement of the electrodes in one patient. CONCLUSION: Unilateral EMCS relieves, at least partially, but sometimes dramatically, the whole spectrum of symptoms in advanced Parkinson's disease. L-Dopa may be reduced up to 70%. The symptoms of long-term L-dopa syndrome are usually markedly improved. The neurophysiological mechanisms involved are still under debate. Our clinical experience adds favorable data to enlarge the series of parkinsonian patients treated by EMCS.

Aged↗

Anesthesia for functional neurosurgery: review of complications.

The use of functional stereotactic neurosurgery is increasing for treatment of patients with movement disorders and other chronic illnesses. The anesthetic considerations include the influence of the anesthetic agents on the microelectrode recordings and stimulation testing of an awake patient. The purpose of this study was to review the anesthetic management and incidences of intraoperative complications during functional neurosurgery in our institution. One hundred seventy-eight patients underwent an ablative procedure (n = 6) or the insertion of deep brain stimulator (n = 172) under monitored anesthesia care for movement disorders (n = 124), chronic pain (n = 20), and other procedures (n = 34). Local anesthetic was used for head frame pin sites and burr holes. No sedation/analgesia was administered to 57 (32%) patients. One patient required conscious sedation and another general anesthesia for the entire procedure. The remainder received small increments (mean +/- SD) of propofol (113 +/- 73 mg), midazolam (1.6 +/- 0.8 mg), and/or fentanyl (93 +/- 55 mug). Intraoperative complications that occurred in 16% of the patients included seizures (n = 8), change in neurologic status (n = 5), airway obstruction (n = 2), and hypertension (n = 7). Functional neurosurgery can be performed with minimal anesthesia in many patients. Awareness and vigilance can improve the identification and early treatment of intraoperative complications such as seizures, loss of airway, and changes in the neurologic status.

Adult↗

Twenty-five years of experience with physiological neurosurgery.

Twenty-five years of experience with physiological neurosurgery for the treatment of movement disorders leads the author to conclude that such syndromes are caused by disordered mechanisms of sensory communication within the brain. The physiological and therapeutic effects of ablation of the posterior portions of the ventrolateral nucleus of the thalamus, the stimulation of the anterior or rostral cerebellar cortex, and deep brain stimulation of some thalamic nuclei are due to the decrease of pathological disinhibition of motor mechanisms. Further advances in the reversal of chronic neurological symptoms by the alleviation of pathological sensory disinhibition are anticipated.

Adult↗

[Three-dimensional atlas of subthalamic nucleus and its adjacent structures].

The deep brain stimulation (DBS) is an effective treatment modality of the functional neurosurgery for disorders such as Parkinson's disease, essential tremor and generalized dystonia. Recently, the targets of DBS for treatment of Parkinson's disease are the thalamus, the Globus pallidus and subthalamic nucleus (STN). The STN-DBS induces improvements in axial motor fluctuation and the on-off phenomenon. The important problem for STN-DBS is that DBS is inserted properly into the STN for good results. The STN is a small body in the deep brain structures. We cannot understand the STN clearly because of its small size and complex shape. The topographical information of deep brain structures has been essential for accurate stereotactic placement of the stimulating electrode of DBS. The target of a deep brain structure is based on the Schaltenbrand and Wahren atlas (S-W atlas). The S-W atlas consists of two-dimensional images such as a coronal section. For this reason, it is difficult to understand localization and the shape of deep brain structures spatially, especially of the subthalamic nucleus on S-W atlas. The three-dimensional image is a useful tool for diagnosis and preoperative planning, because it can easily give neurosurgeons the vivid spatial image of complex structures. We studied a practical use of a three-dimensional atlas of deep brain structures in functional neurosurgery. We devised a three-dimensional atlas to see an image at a free angle on a personal computer. It provided us with more useful information about structures than ones by two-dimentional images. Three-dimensional atlas also helped us make a decision for placement of the deep brain electrode and appropriate electrophysiological recording.

Brain Mapping↗

High-frequency stimulation of the subthalamic nucleus for the treatment of Parkinson's disease--a team perspective.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder affecting more than 1.2 million people in the United States. Genetic and environmental toxins are believed to be risk factors in acquiring the disease. PD is characterized by tremors, rigidity, bradykinesia, poor gait, and postural instability. These cardinal symptoms improve with medication such a levo-dopa (L-dopa). However, over time, as the disease progresses, the patient becomes refractory to medication, or medication produces debilitating side effects. When this occurs or when there are worsening of symptoms, neurosurgical treatment is recommended, particularly deep brain stimulating (DBS) electrodes implanted in the subcortical subthalamic nucleus (STN). Over the last 5 years STN DBS has gained acceptance and become the neurosurgical treatment of choice for PD. To achieve maximum beneficial effects with minimum adverse effects from the surgery, the expertise of an integrated team of physicians and nurses is essential. A clear understanding of the different aspects of the procedure, including the risks and benefits of the treatment, assists neuroscience nurses in communicating with the PD patient, and providing the most appropriate, knowledge-based pre- and postoperative care.

Deep Brain Stimulation↗

Anesthesia for minimally invasive cranial and spinal surgery.

The field of minimally invasive neurosurgery has evolved rapidly in its indications and applications over the last few years. New, less invasive techniques with low morbidity and virtually no mortality are replacing conventional neurosurgical procedures. Providing anesthesia for these procedures differs in many ways from conventional neurosurgical operations. Anesthesiologists are faced with the perioperative requirements and risks of newly developed procedures. This review calls attention to the anesthetic issues in various minimally invasive neurosurgical procedures for cranial and spinal indications. Among the procedures specifically discussed are endoscopic third ventriculostomy, endoscopic transsphenoidal hypophysectomy, endoscopic strip craniectomy, deep brain stimulation, video-assisted thorascopic surgery, vertebroplasty and kyphoplasty, cervical discectomy and foraminectomy, and laparoscopically assisted lumbar spine surgery.

Anesthesia↗