Treatment of pseudobulbar laughter after gamma knife thalamotomy.

We describe a case of pathological laughter after gamma knife thalamotomy which resolved after treatment with sertraline. It is important to identify this potentially treatable complication of surgical therapy.

Thalamic deep brain stimulation: comparison between unilateral and bilateral placement.

BACKGROUND: Unilateral thalamic deep brain stimulation (DBS) is accepted as an effective treatment for essential tremor (ET) and the tremor of Parkinson disease (PD). There are, however, relatively little data concerning bilateral thalamic DBS and no thorough comparisons between the 2 methods. METHODS: To assess the relative benefit of a staged second contralateral DBS placement in patients with PD and ET, we compared preoperative baseline assessments with those at 3 months after the initial implantation, and again at 3 months after the second contralateral implantation. The assessments included the Unified Parkinson's Disease Rating Scale for patients with PD (n = 8) and a modified Unified Tremor Rating Assessment for patients with ET (n = 13). The design included open and blinded (unknown activation status) assessments. RESULTS: Overall, after the second implantation, all specific measures assessing tremor contralateral to that side improved in patients with PD and ET, generally without sacrificing those contralateral to the first side implantation. Midline tremors (face and head) improved only after the second side implantation. In patients with ET, functional and subjective scores tended to further improve after the second placement; however, patients with PD had less subjective improvement. Hand tremor scores in patients with ET randomized to "on" stimulation improved from 6.7 +/- 0.9 to 1.3 +/- 1.2 (P<.005). The scores of patients with PD randomized to on stimulation improved from 9.3 +/- 1.0 to 1.0 +/- 0.5. (Data are given as mean +/- SD.) Tremor scores did not change from baseline in those patients randomized to "off" stimulation in either group. Adverse events related to stimulation increased after the second implantation in both groups. CONCLUSIONS: Bilateral thalamic DBS is more effective than unilateral DBS at controlling bilateral appendicular and midline tremors of ET and PD. Despite this, overall functional disability only improved in patients with ET, possibly secondary to more problematic adverse events in patients with PD, especially balance problems. Bilateral DBS should be considered when unilateral DBS does not offer satisfactory benefit, especially in patients with ET.

[Treatment of dyskinetic disorders with tremor by lesioning and DBS of Vim].

OBJECTIVE: To explore the effect of stereotactic operation in treatment of dyskinetic disorders with tremor as the main symptom and to study the value of anatomic location and microelectrode functional location. METHODS: Surgiplan system and microelectrode direction technique were used to locate the Vim, and then target lesioning and deep brain simulation (DBS) were performed in 22 patients with dyskinetic disorders with tremor. After the operation, a follow-up was conducted for 6 approximately 12 months. RESULTS: After the operation, tremor disappeared in 21 patients and hypermyotonia was improved in 13 cases. During the follow-up tremor completely disappeared in 18 patients, including 3 cases treated with DBS, was markedly alleviated in 3 cases and was slightly improved in one case. Typical cell firing at tremor was recorded in 17 cases during the operation. CONCLUSION: The surgiplan system and microelectrode recording technique play an important role in location of Vim. Accurate location is crucial for success of operation. The curative effect of DBS is similar as lesioning operation.

[Surgical treatment of Parkinson disease and essential tremor]. / Kirurgisk behandling af Parkinsons sygdom og essentiel tremor.

Recognition of the often failing effect of levodopa treatment as Parkinson's disease (PD) progresses has led to the resumption of surgical treatment. In the 1950'ies and 1960'ies pallidotomy and thalamotomy were commonly performed to reduce parkinsonian symptoms, whilst today these permanent lesions are replaced by Deep Brain Stimulation (DBS) of implanted leads. The advantages of DBS in either the subthalamic nuclei (STN) or the internal part of the globus pallidus are that implantation of leads into these nuclei can be performed bilaterally, and that DBS is a reversible treatment. Pallidotomy and thalamotomy are permanent lesions and if performed bilaterally these lesions often cause unacceptable complications. Bilateral stimulation of the STN is often preferred due to the reduction of rigidity, hypokinesia and tremor as well as the significant reduction of dyskinesias and off-periods. The motor functions are significantly improved and stabilized.

[Treatment of severe Parkinson disease with electric stimulation of the subthalamic nuclei]. / Behandling af svaer Parkinsons sygdom med elektrisk stimulation i nucleus subthalamicus.

INTRODUCTION: Patients with Parkinson's disease suffering from severe fluctuations, i.e. dyskinesias and on-off periods and/or severe tremor, who cannot be improved by adjustment of the medical treatment, can be treated with deep brain stimulation via leads implanted bilaterally into the subthalamic nuclei. METHODS: Nine patients with advanced idiopathic Parkinson's disease were treated with stereotactic and bilateral implantation of leads into the subthalamic nuclei. All patients had levodopa responsive Parkinson's disease and levodopa induced fluctuations in the form of on-off periods and dyskinesias. The mean age was 61 years and the mean duration of disease 15 years. The patients were followed for 12 months and evaluated with the Unified Parkinson's Disease Rating Scale off and on medications before and after lead implantation. RESULTS: The Hoehn & Yahr stage fell from 3.9/2.8 before lead implantation and off/on medication to 3.0/2.3 with lead stimulation turned on and off/on medication. The activity of daily living (ADL) index was significantly improved and reduced from 27/13 before lead implantation and off/on medication to 12/7 with the stimulation turned on and off/on medication i.e. with 55%/46% on stimulation. The motor score was likewise significantly improved and reduced from 55/28 to 24/17 i.e. with 56%/39% on stimulation. The most important results of deep brain stimulation in the subthalamic nuclei is the significant reduction of the motor fluctuations. On stimulation off periods were reduced from 30% to 6% and the dyskinesias were significantly reduced from 47% to 14% of the daytime. The mean dose of levodopa equivalent medication was reduced with 26%. DISCUSSION: In conclusion, patients with advanced Parkinson's disease and levodopa induced fluctuations can be successfully treated with bilateral high frequency electric stimulation of leads implanted into the subthalamic nuclei.

Deep brain stimulation reduces symptoms of Parkinson disease.

Surgical ablation or continuous electrical stimulation of specific areas deep in the brain may help patients with Parkinson disease or other movement disorders for whom medications have failed or who experience dose-limiting side effects from medications.

Ablative surgery and deep brain stimulation for Parkinson's disease.

Surgical options for Parkinson's disease (PD) are rapidly expanding and include ablative procedures, deep brain stimulation, and cell transplantation. The target nuclei for ablative surgery and deep brain stimulation are the motor thalamus, the globus pallidus, and the subthalamic nucleus. Multiple factors have led to the resurgence of interest in the surgical treatment of PD: 1) recognition that long-term medical therapy for PD is often unsatisfactory, with patients eventually suffering from drug-induced dyskinesias, motor fluctuations, and variable responses to medication; 2) greater understanding of the pathophysiology of PD, providing a better scientific rationale for some previously developed procedures and suggesting new targets; and 3) use of improved techniques, such as computed tomography- and magnetic resonance imaging-guided stereotaxy and single-unit microelectrode recording, making surgical intervention in the basal ganglia more precise. We review the present status of ablative surgery and deep brain stimulation for PD, including theoretical aspects, surgical techniques, and clinical results.

Targeting the subthalamic nucleus in the treatment of Parkinson's disease.

As more is learnt about the functional implications of basal ganglia connectivity, the role of the subthalamic nucleus as a target site for stereotactic procedures in the amelioration of the symptoms of Parkinson's disease is becoming clearer. A comparison of various neurosurgical procedures in the disease is discussed in relation to current thinking about circuitry. Experimental investigations involving lesioning or stimulation of the subthalamic nucleus in nonhuman primate models and in clinical studies of Parkinson's disease are compared. Neurosurgical procedures that lesion structures bilaterally are more likely to induce side effects than is deep-brain stimulation, which has the added advantage of reversibility and which is more amenable to titration in relation to medication and dosage. A small but growing number of parkinsonian patients have received subthalamic stimulation either unilaterally or bilaterally. Stimulation of the subthalamic nucleus ameliorates tremor, rigidity and hypokinesia, as opposed to thalamic stimulation which is probably best reserved for tremor-dominant patients. Such procedures also do not involve the same complex technical and ethical issues that are associated with foetal mesencephalic grafting. Although subthalamic stimulation shows great promise, it has not been developed to the point where it can be used as more than an experimental treatment. Further experimental research is required before the new strategies can be used on a larger scale.

Effect of electrical stimulation of the thalamic Vim nucleus on hand tremor during stereotactic thalamotomy.

OBJECTIVE: The aim of this study was to analyze the correlation between neuronal responses in the thalamic ventralis intermedius (Vim) nucleus to peripheral, natural stimulation and the modulation of tremor by electrical stimulation during stereotactic thalamotomy. DESIGN AND METHODS: The authors studied 36 patients with hand tremor using a microelectrode. The responses of tremor to electrical stimulation were analysed electromyographically. Sixty stimulation sites were divided into three groups. RESULTS: Group A (20 sites) where responses to stretching of the contralateral forearm muscles were recorded. Group B (26 sites) where responses to stretching of the other muscles of the upper extremity were recorded. Electrical stimulation at sites in groups A and B temporarily suppressed the contralateral tremor, but the minimum current intensity to suppress tremor at sites in group A was less than that in group B. Electrical stimulation in group C (14 sites), where kinesthetic responses of contralateral lower extremity were recorded, resulted in increased amplitude of hand tremor. Selective coagulation including the area of tremor suppression resulted in abolition of the tremor in all patients. CONCLUSIONS: These results suggest that the most effective site for thalamotomy may also be suitable for chronic stimulation in the Vim nucleus.

Gamma knife radiosurgery for thalamotomy in parkinsonian tremor: a five-year experience.

OBJECT: Certain patients, for example, elderly high-risk surgical patients, may be unfit for radiofrequency thalamotomy to treat parkinsonian tremor. Some patients, when given the opportunity, may choose to avoid an invasive surgical procedure. The authors retrospectively reviewed their experience using gamma knife radiosurgery for thalamotomies in this patient subpopulation: 1) to determine the efficacy of the procedure; 2) to see if there is a dose-response relationship; 3) to review radiological findings of radiosurgical lesioning; and 4) to assess the risks of complications. METHODS: Radiosurgical nucleus ventralis intermedius thalamotomy using the gamma knife unit was performed to make 38 lesions in 24 men and 10 women (median age 73 years, range 58-87 years) over a 5-year period. A median radiation dose of 130 Gy (range 100-165 Gy) was delivered to 38 nuclei (four patients underwent bilateral thalamotomy) using a single 4-mm collimator following classic anatomical landmarks. Twenty-nine lesions were made in the left nucleus ventralis intermedius thalamus for right-sided tremor. Patients were followed for a median of 28 months (range 6-58 months). Independent neurological evaluation of tremor based on the change in the Unified Parkinson's Disease Rating Scale tremor score was correlated with subjective patient evaluation. Comparison was made between a subgroup of patients in whom "low-dose" lesions were made (range 110-135 Gy, mean 120 Gy) and those in whom "high-dose" lesions were made (range 140-165 Gy, mean 160 Gy) for purposes of dose-response information. Four thalamotomies (10.5%) failed, four (10.5%) produced mild improvement, 11 (29%) produced good improvement, and 10 (26%) produced excellent relief of tremor. In nine thalamotomies (24%) the tremor was eliminated completely. The median time to onset of improvement was 2 months (range 1 week-8 months). Concordance between an independent neurologist's evaluation and that of the patient was statistically significant (p < 0.001). Two patients who underwent unilateral thalamotomy experienced bilateral improvement in their tremor. There were no neurological complications. There was better tremor reduction in the high-dose group than in the low-dose group (p < 0.04). CONCLUSIONS: Although less effective than other stereotactic techniques, gamma knife radiosurgery for thalamotomy offers tremor control with minimal risk to patients unsuited for open surgery.

Neural activity of the subthalamic nucleus in Parkinson's disease patients.

The neural activity pattern of the subthalmic nucleus (STN) was investigated in five patients with Parkinson's disease who were scheduled for electrode implantation for chronic stimulation of the STN. The initial target was placed 8 mm or 10 mm lateral to the midline, 3 mm to 4 mm posterior to the midcommissural point, and 5 mm to 6 mm below the intercommissural (AC-PC) line. The STN was identified by semi-microelectrode recordings with a trajectory moving laterally in 2-mm steps. The amplitudes of multi-unit activities were relatively low at depths from 8 mm to 5 mm above and from 1 mm to 4 mm below the target, while those 4 mm to 0 mm above the target were significantly higher than at the other sites (ANOVA, Fisher's test, p < 0.05), with the highest amplitude at 2 mm above the target (91.0 +/- 23.3 mu v, n = 15). In the mediolateral direction, amplitudes were relatively higher in the lateral portion, and amplitudes at 14 mm lateral to the midline were significantly higher than at the other sites (ANOVA, Fisher's test, p < 0.05). The target for chronic electrical stimulation was determined to be at the midpoint of the hyperactive STN, i.e., 12 mm lateral to the midline in three patients and 13 mm lateral in two patients. Movement-related neural activity was observed at 5 sites, i.e., 3 sites responded to passive movement of the contralateral wrist and 2 sites to passive knee and/or ankle movement. In conclusion, our data show that the lateral part of the STN is hyperactive in PD, and recordings of neural activities contributed greatly to identifying the STN and determining the target for chronic stimulation within it.

[Neurosurgical methods in treatment of Parkinson disease. Current status]. / Neurochirurgische Verfahren zur Behandlund des Morbus Parkinson. Eine Bestandsaufnahme.

There is a world-wide renaissance of neurosurgical treatments of Parkinson's disease (PD), based on substantial progress in basic sciences. A model of parallel motor circuitry has identified potential targets for lesioning by clarifying the pathophysiological role of the basal ganglia in PD. The internal globus pallidus (Gpi) is an essential player as it connects to thalamocortical projections and can be disinhibited by overactivity of the nucleus subthalamicus (Nst). Lesioning of these targets has been successful in MPTP damaged primates. There is clinical use of destructive as well as restorative and stimulative technics. Pallidotomy and thalamatomy have evolved by the use of better neuroradiological and electrophysiological targeting. The first technic is used for treatment of rigidity, hypokinesia and dyskinesias, the latter one has proven to be efficient for tremor. Dopaminergic reinnervation and increased dopaminergic output of the striatum has only been seen after transplantation of fetal cells; this method however carries immunological and ethical problems. The continuous high frequency stimulation of basal ganglia is the newest technic; it is highly adaptable to the patient's need and carries a low morbidity profile. Thalamic stimulation is used for the treatment of tremor. The stimulation of Nst and Gpi are proposed for dyskinesias and on/off phenomena. Animal research further focuses on xenotransplantation and implantation of genetically transformed cells or pluripotent precursor cells.--In summary neurosurgical procedures seem to be very promising; however longterm comparison studies are needed to define the best (combination) treatment(s) for the future.

Pallidotomy revisited. Analysis of posteroventral pallidotomy.

Posteroventral pallidotomy (PVP) has been shown to alleviate motor symptoms in Parkinson's disease (PD), e.g., rigidity, secondary akinesia due to existence of muscle rigidity and slight tremor, but not the marked tremor. For the latter, additional lesion of the ventral intermediate nucleus of the thalamus is necessary. Akinesia was divided into three subtypes, and the influence of PVP on each type is described. Primary akinesia is not changed by either PVP or thalamotomy but responds well to L-dopa. Psychological symptoms, i.e., depressive mood, loss of initiation or abulia, and lowered emotional activity, which are generally termed as bradyphrenia, benefit well from PVP but less from thalamotomy. This effect is interpreted as due to the lesion extending into the ventral pallidum, where a small posterior part of the limbic-motor projections may possibly be involved. Such experience suggests that the third type of akinesia in PD, named the 'psychomotor or limbic-motor type' by the author, can be improved by the surgical procedure on the ventral globus pallidus. These observations offer an important chance to understand the psychological symptoms in PD as a result of dopamine deficiency of ventral tegmental area neurons projecting to the ventral striatum, which further influences the ventral pallidum.

Deep brain stimulation for essential tremor.

We examined the effects and safety of deep brain stimulation (DBS) as a treatment for essential tremor (ET). Ten ET patients with disabling medication-refractory tremor underwent stereotactic implantation of a DBS lead in the left Vim thalamic nucleus and completed a 6-month follow-up. The Clinical Tremor Rating Scale and disability assessments were performed at baseline, 1-, 3-, and 6-month follow-up. There were significant improvements in dressing, drinking, eating, bathing, and handwriting as reported by the subjects. Tremor severity, writing, pouring, and spiral and line drawing were significantly improved as rated by the examiner. Improvements persisted through the 6-month follow-up period. Although global disability significantly lessened in the group as a whole, one subject with hand-finger tremor accentuated by writing had no change in disability status. In this 6-month open-label study, DBS was effective and safe in reducing tremor and functional disability in ET.