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PubMed2003

Update on cluster headache.

PURPOSE OF REVIEW: Although cluster headache has traditionally been thought of as a vascular headache disorder, its periodicity suggests an involvement of central areas such as the hypothalamus. This review covers the past 3 years, which have seen remarkable progress in understanding the pathophysiology of circadian headache syndromes and have brought exciting news. RECENT FINDINGS: As more cluster headache patients are seen by headache specialists, new forms of this well-defined primary headache syndrome are being identified. In addition, we discuss recent findings with regard to abnormalities in the secretion of hormones, genetic influences, neuroimaging of cluster headache attacks, and the use of newer substances as preventive therapy in cluster headache. SUMMARY: We have entered a new diagnostic and therapeutic era in primary headache disorders. In recent reports, the use of deep brain stimulation of the hypothalamus has enabled intractable chronic cluster headache patients to be successfully operated upon. Further research in this field is urgently needed and the recent possibility of combining deep brain stimulation with positron emission tomography will certainly help to unravel the brain circuitry implicated in stimulation-produced analgesia. The time has come to use the evidence for a disorder of circadian rhythm in cluster headache to further the development of chronobiotics in the treatment of this disorder.

Cluster Headache↗

PubMed2006

Two cases of ischemia associated with subthalamic nucleus stimulator implantation for advanced Parkinson's disease.

Deep brain stimulation is generally a safe and effective method of alleviating motor impairment in advanced-stage Parkinson's disease patients. However, adverse events of surgery have been noted, such as hemorrhage, infection, seizures, and device failure. In this report, we describe 2 cases of the unusual adverse event of ischemia associated with subthalamic nucleus stimulator implantation. We present the intraoperative neurological symptoms, microelectrode recording data, imaging findings, and other correlated events. In the first case, the clinical effects of ischemia were evident intraoperatively and coincided with silence during microelectrode recording from the ischemic region. In the second case, the timing of the ischemic event could not be determined precisely but also was associated with a difficult mapping. Subcortical ischemia may be an underrecognized event that confounds neurophysiological mapping of deep brain structures and affects clinical outcomes.

Aged↗

PubMed2005

Suppression of secondary generalization of limbic seizures by stimulation of subthalamic nucleus in rats.

OBJECT: Deep brain stimulation (DBS) of subcortical nuclei such as the subthalamic nucleus (STN) or the substantia nigra pars reticulata (SNR) may provide an alternative therapy for intractable epilepsy. The authors attempted to evaluate the antiepileptic effects of DBS to these structures in an experimental seizure model. METHODS: Three groups of rats were prepared. In the first two groups, the rats underwent unilateral implantation of stimulation electrodes in the STN (six rats) or the SNR (six rats). A control group received no electrodes (six rats). Kainic acid (KA) was systemically administered to induce limbic seizures, which started with focal seizures and became generalized secondarily. High-frequency electrical stimulation of the STN or SNR was begun immediately after KA administration, and changes on electroencephalography (EEG) and the magnitude of clinical seizures were evaluated. Results showed that STN stimulation significantly reduced the duration of generalized seizures on EEG, although the total duration of seizures (generalized plus focal seizures) was unchanged. The duration of focal seizures on EEG was prolonged by STN DBS, a result possibly due to the suppression of secondary generalization. In addition, STN DBS reduced the severity of clinical seizures. On the other hand, stimulation of the SNR demonstrated no effect. CONCLUSIONS: Unilateral STN DBS showed significant suppression of the secondary generalization of limbic seizures. Note, however, that SNR DBS was less effective, which implies that in addition to the nigral control of the epilepsy system, another antiepileptic mechanism such as antidromic stimulation of the corticosubthalamic pathway should be considered.

Animals↗

PubMed2006

Subthalamic nucleus stimulation: improvements in outcome with reprogramming.

BACKGROUND: Deep brain stimulation (DBS) is currently the most effective surgical treatment for advanced Parkinson disease (PD). Even when the electrode is well positioned in the target, the optimization of clinical results depends on careful programming of electrical parameters and changes in antiparkinsonian drug dosages. OBJECTIVE: To determine whether stable outcomes from subthalamic nucleus DBS for PD can be improved by revising stimulation parameters and drug dosages through "hands-on" involvement of a neurologist expert in both movement disorders and DBS programming. METHODS: In 44 consecutive patients with PD with long-term stable response to subthalamic nucleus DBS (mean +/- SD, 3.5 +/- 1.7 years), we compared scores from the Unified Parkinson's Disease Rating Scale parts II through IV obtained immediately before and following a formal reprogramming of their stimulation. The reprogramming was performed by a neurologist expert in both PD and DBS and accompanied by further medication adjustments. The patients were subsequently followed up for as long as 14 months. RESULTS: In 24 patients (54.6%), the scores on the Unified Parkinson's Disease Rating Scale parts II and III significantly improved by 15.0% and 25.9%, respectively. Anti-PD drugs were significantly reduced (by 25.9%). No improvement was observed in 16 patients (36.4%), and the conditions of 4 patients (9.1%) worsened. CONCLUSIONS: Further improvement of parkinsonian signs can be achieved in the majority of patients even after long-term stable stimulation. Improved patient outcomes from subthalamic nucleus DBS are obtained when postoperative care is personally managed by a neurologist expert in movement disorders and DBS who is directly responsible for stimulation programming and simultaneous drug adjustments based on observed clinical responses to changing stimulation parameters.

Antiparkinson Agents↗

PubMed2004

Improvement of apraxia of lid opening by STN-stimulation in a 70-year-old patient with Parkinson's disease. A case report.

We report on a 70-year-old female patient with Parkinson's disease, who showed an improvement of a preexisting apraxia of lid opening on electrical impulses, so-called deep brain stimulation (DBS) delivered to the subthalamic nucleus (STN). This was not described by any other authors before. Up to now, the appearance of apraxia of lid opening was observed only as a side effect after deep brain stimulation in the nucleus subthalamicus. We suggest that these differences may be due to the region of the nucleus subthalamicus that is influenced by the stimulation.

Aged↗

PubMed2003

Synaptic plasticity in rat subthalamic nucleus induced by high-frequency stimulation.

The technique of deep brain stimulation (DBS) has become a preferred surgical choice for the treatment of advanced Parkinson's disease. The subthalamic nucleus (STN) is presently the most promising target for such DBS. In this study, whole-cell patch-clamp recordings were made from 46 STN neurons in rat brain slices to examine the effect of high-frequency stimulation (HFS) of the STN on glutamatergic synaptic transmission in STN neurons. HFS, consisting of trains of stimuli at a frequency of 100 Hz for 1 min, produced three types of synaptic plasticity in 17 STN neurons. First, HFS of the STN induced short-term potentiation (STP) of evoked postsynaptic current (EPSC) amplitude in four neurons. STP was associated with a reduction in the EPSC paired-pulse ratio, suggesting a presynaptic site of action. Second, HFS of the STN generated long-term potentiation (LTP) of EPSC amplitude in eight neurons. Although the EPSC paired-pulse ratio was reduced transiently in the first 2 min following HFS, ratios measured 6-20 min after HFS were unchanged from control. This suggests that LTP is maintained by a postsynaptic mechanism. Third, HFS produced long-term depression (LTD) of EPSC amplitude in five STN neurons. LTD was associated with a significant increase in EPSC paired-pulse ratios, indicating a presynaptic site of action. These results suggest that HFS can produce long-term changes in the efficacy of synaptic transmission in the STN. HFS-induced synaptic plasticity might be one mechanism underlying the effectiveness of DBS in the STN as a treatment of advanced Parkinson's disease.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2000

Neuropsychological functioning in a patient with essential tremor with and without bilateral VIM stimulation.

The effects of deep brain stimulation on motor functions, cognitive abilities, and mood were assessed in an 80-year-old, right-handed male with a chronic history of essential tremor. Electrodes were implanted bilaterally in the ventral intermediate nucleus of the thalamus during a single operation. Upon evaluation at 3 months postsurgery, bilateral stimulation was associated with a clinically significant reduction in tremor ratings and improvement in manual dexterity. At that time, a battery of neuropsychological measures was administered with and without bilateral stimulation. The patient demonstrated comparable performances on measures of visuospatial perception, attention, mental tracking, verbal learning, and verbal recognition memory in both the "on" and "off" conditions. Without stimulation, the patient demonstrated declines of greater than 1 SD on measures of verbal fluency and verbal recall compared to when the stimulators were active. Responses to mood rating scales also indicated greater subjective distress without stimulation. Results are discussed in the context of previous studies of the effects of thalamic stimulation on neurocognitive functioning.

Aged↗

PubMed2006

A dominant bursting electromyograph pattern in dystonic conditions predicts an early response to pallidal stimulation.

Although chronic pallidal deep brain stimulation (DBS) is effective in the treatment of medically intractable dystonia, there is no way of predicting the variations in clinical outcome, partly due to our limited understanding of the pathophysiological mechanisms underlying this condition. We recorded electromyographic (EMG) activity from the most severely affected muscle groups in seven dystonia patients before and after pallidal DBS. Patient EMG recordings could be classified into two groups: one consisting of patients who at rest demonstrated a dominant low frequency component of activity on power spectral analysis (ranging from 2 to 5 Hz), and one group in which this dominant pattern was absent. Early postoperative improvements (within 2-3 days) were observed in the former group, whereas the latter group benefited more gradually (over several months). Analysis of EMG activity may provide a sensitive means of identifying dystonic patients who are likely to be most responsive to functional neurosurgical intervention.

Action Potentials↗

PubMed2002

[Parkinson disease: deep cerebral stimulation].

The effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal pallidum (GPi) on the parkinsonian triad and on levodopa-induced dyskinesias are very similar. The antiakinetic effect of STN DBS seems to be slightly better. On the contrary to pallidal DBS, stimulation of the STN allows to reduce dopaminergic treatment by more than 50 p. 100 on average. Moreover, the current drain is smaller in STN. Thus, the STN is a low budget target compared to the GPi. STN DBS seems to be as effective on PD tremor as stimulation of the classic thalamic target, the ventral intermediate nucleus (Vim), whereas Vim stimulation has no effect on akinesia and very little on levodopa-induced dyskinesias. Thus, the STN has become the main target nucleus for DBS in PD, which is most often performed bilaterally in one surgical procedure. There is a good correlation of the preoperative response to levodopa and postoperative effects of bilateral STN DBS and this defines the patient population. Given the large patient population, simple guidelines for patient selection are developed. The referring physician can preselect patients based mainly on age (less than 70), absence of dementia and presence of severe disability related to motor fluctuations or dyskinesias. It is the responsibility of the operating centre to determine the levodopa response, to confirm the diagnosis, to rule out contraindications and to make sure that the medical treatment cannot be further optimised. Severe surgical complications with permanent sequels are relatively rare, about 1 p. 100 per implanted side. The patient selection, the precision of the surgery and the quality of the postoperative follow-up are the three main determinants of success.

Adult↗

PubMed2004

Pallidal stimulation for dystonia.

OBJECTIVE: High-frequency deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a new and promising treatment option for severe dystonia. Yet only few studies have been published to date regarding this treatment. We present the results of DBS of the GPi in 17 patients with severe dystonia of different causes. METHODS: In our study, we included 10 patients with primary generalized dystonia, six patients with secondary generalized dystonia, and one patient with a severe dystonic cervical tremor. In all patients, DBS electrodes were implanted bilaterally within the GPi. Mean follow-up time was 36 months (range, 12-66 mo). Preoperative and postoperative evaluations (at least annually) were performed using the Burk-Fahn-Marsden scale. RESULTS: The best improvement was achieved in patients with DYT1-positive dystonia. Patients with DYT1-negative generalized dystonia showed inhomogeneous results. There was no significant change in patients with tardive dystonia. One case of Hallervorden-Spatz disease improved dramatically within the first 2 years. The improvement in the cervical dystonic tremor was disappointing, however. Three years after DBS implantation, we found a secondary worsening of symptoms in one patient with a DYT1-positive dystonia and in the patient with Hallervorden-Spatz disease. CONCLUSION: DBS of the GPi is a new and promising treatment option for dystonia. Secondary worsening may limit this therapy.

Adolescent↗

PubMed2004

[Surgical treatment for Parkinson's disease].

In the past years there has been an increasing interest in the surgical therapies for Parkinson's disease. This renewed interest is related to differents factors. First, pharmacological treatments are still unable to alter substantially the progression of the disease and after a few years they generally cause motor complications and dyskinesias. Secondly, the great advances in the surgical techniques, especially with the improvement of stereotactic surgery, have decreased morbidity in recent years. Finally, the introduction of deep brain stimulation, now allows surgical treatment without damaging brain structures. In this review, different surgical treatments are summarized. Ablative surgery, deep brain stimulation and reinervation therapies are described.

Animals↗

PubMed1999

Surgical treatment of Parkinson's disease.

Stereotaxtic surgery is an effective therapeutic maneuver in the management of advanced Parkinson's disease (PD). Thalamotomy is an effective measure to control tremor but other PD symptoms are not changed. Bilateral operations are associated with a risk of severe speech impairment. Deep brain stimulation (DBS) of the thalamus is as effective as thalamotomy and is associated with fewer side effects. Pallidotomy is effective in reducing contralateral dyskinesias and the cardinal symptoms of PD. Bilateral pallidotomy often results in cognitive dysfunction. Deep brain stimulation of the pallidum replicates the positive effects of pallidotomy and appears to be safer than ablative lesions. Subthalamic DBS is currently under investigation. This procedure may control all PD symptoms, and the dose of levodopa can often be dramatically reduced. Neurotransplantation is a promising surgical approach to PD. However, further investigation is needed to optimize this approach.

Brain Tissue Transplantation↗

PubMed2006

Emerging treatments for depression.

Established treatments for depression are often effective. However, a significant number of patients show limited or no response. With advancements in the explanation of the underlying neurobiology of depression, several novel therapeutic approaches have been developed. Emerging drug targets include novel monoamine oxidase inhibitors, triple monoamine re-uptake inhibitors, omega-3 fatty acids, melatoninergic agonists and receptor antagonists for corticotropin-releasing factor(1), glucocorticoid, substance-P and NMDA. Developments in therapeutic focal brain stimulation include vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy and deep brain stimulation. The role of psychotherapy, both as monotherapy and as adjunctive therapy, is an active avenue of investigation. Although data on these treatments are limited, preliminary results are encouraging. A major goal that remains to be achieved is the identification of predictors of response to the various antidepressant treatments that have diverse mechanisms of action.

Antidepressive Agents↗

PubMedDate not supplied

[Treatment of a case of generalised dystonia using subthalamic stimulation].

INTRODUCTION: Generalised dystonia is an entity that does not usually respond well to medical treatment. Different surgical targets have therefore been used in the treatment of dystonia, including several thalamic nuclei or the internal globus pallidus. The subthalamic nucleus plays a fundamental role in the physiology of the basal ganglia. It could therefore be considered to be a good potential target for stimulation. CASE REPORT: A patient who was confined to a wheelchair and who had not responded to a number of different medical treatment protocols or to a bilateral thalamotomy was treated with bilateral deep brain stimulation in the subthalamic nucleus. Tetrapolar electrodes were placed in both subthalamic nuclei in two stages. The patient showed a significant improvement from the very beginning of the post-operative period. After six months' progression, the patient was able to walk unaided and the dystonic seizures diminished significantly. Unfortunately, the patient died from choking. We used a bipolar stimulation protocol at 50 Hz with 210 micros pulses, which do not reach the levels of maximum charge density that are considered to be harmful. CONCLUSION: The subthalamic nucleus can be a good surgical target for deep brain stimulation in cases of generalised dystonia; it responds well to stimulation at intermediate frequencies with safe charge densities.

Dystonia↗

PubMed2004

[Update on neurosurgical treatment for obsessive compulsive disorder].

Responses to pharmacotherapy and psychotherapy in obsessive-compulsive disorder (OCD) range from 60 to 80% of cases. However, a subset of OCD patients do not respond to adequately conducted treatment trials, leading to severe psychosocial impairment. Stereotactic surgery can be indicated then as the last resource. Five surgical techniques are available, with the following rates of global post-operative improvement: anterior capsulotomy (38-100%); anterior cingulotomy (27-57%); subcaudate tractotomy (33-67%); limbic leucotomy (61-69%), and central lateral thalamotomy/anterior medial pallidotomy (62.5%). The first technique can be conducted as a standard neurosurgery, as radiosurgery or as deep brain stimulation. In the standard neurosurgery neural circuits are interrupted by radiofrequency. In radiosurgery, an actinic lesion is provoked without opening the brain. Deep brain stimulation consists on implanting electrodes which are activated by stimulators. Literature reports a relatively low prevalence of adverse events and complications. Neuropsychological and personality changes are rarely reported. However, there is a lack of randomized controlled trials to prove efficacy and adverse events/complication issues among these surgical procedures. Concluding, there is a recent development in the neurosurgeries for severe psychiatric disorders in the direction of making them more efficacious and safer. These surgeries, when correctly indicated, can profoundly alleviate the suffering of severe OCD patients.

Humans↗

PubMed1999

Cognitive outcome after unilateral pallidal stimulation in Parkinson's disease.

OBJECTIVES: Chronic high frequency electrostimulation of the globus pallidus internus mimics pallidotomy and improves clinical symptoms in Parkinson's disease. The aim of this study was to investigate the cognitive consequences of unilateral deep brain stimulation. METHODS: Twenty non-demented patients with Parkinson's disease (age range 38-70 years) were neuropsychologically assessed 2 months before and 3 months after unilateral pallidal stimulation. The cognitive assessment included measures of memory, spatial behaviour, and executive and psychomotor function. In addition to group analysis of cognitive change, a cognitive impairment index (CII) was calculated for each individual patient representing the percentage of cognitive measures that fell more than 1 SD below the mean of a corresponding normative sample. RESULTS: Neurological assessment with the Hoehn and Yahr scale and the unified Parkinson's disease rating scale disclosed a significant postoperative reduction in average clinical Parkinson's disease symptomatology (p<0.001). Repeated measures multivariate analysis of variance (using right/left side of stimulation as a between subjects factor) showed no significant postoperative change in cognitive performance for the total patient group (main effect of operation). The side of stimulation did not show a significant differential effect on cognitive performance (main effect of lateralisation). There was no significant operation by lateralisation interaction effect. Although the patients experienced significant motor symptom relief after pallidal stimulation, they remained mildly depressed after surgery. Analysis of the individual CII changes showed a postoperative cognitive decline in 30% of the patients. These patients were significantly older and took higher preoperative doses of levodopa than patients showing no change or a postoperative cognitive improvement. CONCLUSIONS: Left or right pallidal stimulation for the relief of motor symptoms in Parkinson's disease seems relatively safe, although older patients and patients needing high preoperative doses of levodopa seem to be more vulnerable for cognitive decline after deep brain stimulation.

Adult↗

PubMed2005

An effect of dopamine depletion on decision-making: the temporal coupling of deliberation and execution.

When a decision between alternative actions has to be made, the primate brain is able to uncouple motor execution from mental deliberation, providing time for higher cognitive processes such as remembering and reasoning. The mental deliberation leading to the decision and the motor execution applying the decision are likely to involve different neuronal circuits linking the basal ganglia and the frontal cortex. Behavioral and physiological studies in monkeys indicate that dopamine depletion may result in a loss of functional segregation between these circuits, hence, in interference between the deliberation and execution processes. To test this hypothesis in humans, we analyzed the movements of parkinsonian patients in a go/no-go task, contrasting periods of uncertainty with periods of knowledge about the rule to be applied. Two groups of patients were compared to healthy subjects: one group was treated with dopaminergic medication and the other with deep brain stimulation; both groups were also tested without any treatment. In healthy subjects, the movement time was unaffected by uncertainty. In untreated patients, the movement time increased with uncertainty, reflecting interference between deliberation and execution processes. This interference was fully corrected with dopaminergic medication but was unchanged with deep brain stimulation. Moreover, decision-related hesitations were detectable in the movements of dopamine-depleted patients, revealing a temporal coupling of deliberation and execution. We suggest that such coupling may be related to the loss of dopamine-mediated functional segregation between basal ganglia circuits processing different stages of goal-directed behavior.

Aged↗

PubMed2006

Advances in the treatment of depression.

SUMMARY: Depression is a highly prevalent and disabling condition associated with significant morbidity and mortality. Currently available treatments for depression include tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, various atypical antidepressants, and electroconvulsive therapy. Although these treatments are effective, a significant number of patients do not respond or achieve sustained remission despite aggressive management. Advances in the neurobiology of depression have suggested a number of novel targets for antidepressant treatment. Based on an improved understanding of the neurobiology of depression, several novel pharmacologic and nonpharmacologic interventions are being developed. Pharmacologic developments include CRF antagonists, glucocorticoid receptor antagonists, substance P receptor antagonists, NMDA glutamate receptor antagonists, transdermal selegiline, so-called "triple" reuptake inhibitors, and augmentation of typical antidepressant medications with atypical antipsychotics. Nonpharmacologic advances have largely involved focal brain stimulation techniques including vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, and deep brain stimulation. For the most part, the data on these treatments are preliminary, and more study is needed to clarify their potential clinical benefit. However, it is clear that further study of the neurobiology of depression will continue to provide a rationale for developing innovative targets for antidepressant therapies.

Antidepressive Agents↗