Deep brain stimulation of the Vim nucleus of the thalamus for the treatment of tremor.

The surgical treatment of tremor has evolved considerably in the past few years. Of the several conditions associated with severe tremor, the most common are Parkinson's disease (PD) and essential tremor (ET). Levodopa therapy reduced drastically the number of patients with PD who require surgery because of inadequate control. However, there remains a small number of "tremor dominant" PD patients for whom surgical treatment is often the best option. The ventralis intermediate nucleus (Vim) of the thalamus has been the preferred surgical target for the treatment of parkinsonian tremor for many years, but this is now challenged by the subthalamic nucleus (STN). Deep brain stimulation (DBS) of either target possesses high therapeutic efficacy against tremor in PD. ET may be difficult to treat pharmacologically. Thalamotomy is an effective surgical procedure for ameliorating ET but may be associated with persistent neurologic deficits. DBS of the thalamus is also a highly effective means of reducing ET. DBS appears to be safer than thalamotomy and is now the recommended surgical procedure.

Unilateral pallidal stimulation for Parkinson's disease: neurobehavioral functioning before and 3 months after electrode implantation.

Unilateral pallidotomy is thought to have a low risk for cognitive morbidity. Nonetheless, recent research suggests that some patients experience declines in memory and language and that pallidal stimulation might be a safer treatment for Parkinson's disease (PD). We investigated the neurobehavioral effects of unilateral pallidal stimulation. Nine consecutive PD patients undergoing unilateral deep brain-stimulating electrode implantation in the globus pallidus interna were evaluated with a neuropsychological test battery approximately 1 month before and 3 months after surgery. Patients reported significantly fewer symptoms of anxiety and greater vigor after surgery. There was a trend toward fewer depressive symptoms. Semantic verbal fluency and visuoconstructional test scores declined significantly after surgery. However, among five patients showing declines in semantic verbal fluency, only one patient's score declined by more than 2 SD. No patient showed significant decline or improvement in the overall level of cognitive functioning. This study supports the relative safety, in terms of cognitive function, of unilateral pallidal stimulation in PD.

Reduction in voice tremor under thalamic stimulation.

We studied the effect of deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus on voice symptoms in seven patients with essential tremor. All had undergone DBS for management of hand tremor. Five of the patients had received unilateral implants; two were treated bilaterally. Each reported improvement in hand tremor with thalamic stimulation (a 1-to-3-point change on a 5-point severity scale). Voice tremor was evaluated with and without stimulation using patient and clinician severity ratings, and acoustic measures (rate and amplitude). Four of the seven patients showed reductions in voice symptoms in at least two of these measures, although degree of change differed (e.g., from 1 to 3 points on the 5-point severity scale). Voice gains typically were restricted to those patients with the more severe symptoms and did not parallel improvements in the upper extremities. It appears that reduced voice tremor may be an additional benefit of DBS for some individuals.

Bilateral thalamic stimulation for the treatment of essential tremor.

OBJECTIVE: To determine the safety and efficacy of bilateral thalamic stimulation in the treatment of essential tremor (ET). METHODS: Nine ET patients with disabling tremor refractory to pharmacotherapy underwent bilateral staged implants. Tremor was assessed by the Fahn-Tolosa-Marin Tremor Rating Scale at baseline 1 (before first implant), baseline 2 (before second implant), and at 6-month and 1-year follow-up. Blinded evaluations were performed at 3 months. Associated changes in speech were evaluated in six patients. There were seven men and two women with a mean age of 73.8 years. RESULTS: There was a significant improvement in the mean total tremor score from a baseline of 66.1+/-11.6 to 28.4+/-12.8 12 months after the second surgery. Similarly, the mean motor tremor subscore was 20.1+/-5.0 before the first surgery and improved significantly to 14.1+/-3.6 before the second surgery. Motor tremor scores 6 months after the second surgery (6.0+/-3.7) and 12 months after the second surgery (7.5+/-3.9) also improved significantly relative to the preoperative scores. The mean activities of daily living (ADL) subscore at baseline was 18.2+/-2.9 and improved significantly before the second surgery to 9.0+/-3.2. These ADL scores further improved 6 months (6.2+/-5.2) and 12 months (7.9+/-5.7) following the second surgery, but these gains were not significant. Blinded evaluations also revealed a similar degree of improvement. Complications were noted in five patients: asymptomatic intracranial hematoma (1), postoperative seizures (1), a hematoma over the implanted pulse generator (IPG) (1), lead repositioning (1), and IPG malfunction (1). Adverse effects related to stimulation were mild and resolved with adjustment of the stimulation parameters. Three of the six patients demonstrated worsening of dysarthria with both stimulators on. CONCLUSIONS: Bilateral thalamic stimulation is effective in reducing tremor and functional disability in ET; however, dysarthria is a possible complication.

Neuropsychological and quality of life outcome after thalamic stimulation for essential tremor.

OBJECTIVE: To evaluate short-term effects of unilateral thalamic deep brain stimulation (DBS) on cognition, mood state, and quality of life in patients with essential tremor (ET). BACKGROUND: Unilateral thalamotomy and thalamic DBS are effective in alleviating refractory tremor contralateral to the side of surgery. Thalamotomy can lead to cognitive morbidity, and DBS might be a preferable surgical intervention given potential avoidance or reversibility of such morbidity. Although unilateral thalamic DBS is cognitively safe and leads to quality of life improvement in PD, its neurobehavioral effects in ET are unknown. METHODS: Forty patients with ET were administered a broad neuropsychological test battery, measures of mood state, and generic and disease-specific quality of life measures approximately 1 month before and 3 months after surgery (left hemisphere, 38 patients). RESULTS: Unilateral thalamic DBS was associated with significant improvements in tremor and dominant-hand fine visuomotor coordination. Statistically significant but clinically modest gains were observed on tasks of visuoperceptual and constructional ability, visual attention, delayed word list recognition, and prose recall. Only lexical verbal fluency declined significantly after surgery. Patients rated themselves as less anxious after surgery, and they perceived their quality of life as improved significantly. In particular, patients reported improved quality of life with respect to activities of daily living, stigma, emotional well-being, and communication. CONCLUSIONS: Unilateral thalamic DBS for ET is cognitively safe and associated with improvements in anxiety and quality of life in the near term and in the absence of operative complications. Patients were better able to carry out activities of daily living after surgery, and they reported improvement in several psychosocial domains of quality of life.

Rhabdoid transformation of tumor cells in meningiomas: a histologic indication of increased proliferative activity: report of four cases.

Four cases of meningeal tumors in adults (ages ranging from 28 to 84 years) are presented. All had the typical gross appearance of meningiomas at operation. In three tumors, areas of meningothelial or fibroblastic meningiomas showed transition to cell groups of the rhabdoid type. In the fourth case only rhabdoid cells were encountered, possibly representing a total "take-over" of a meningioma by rhabdoid elements. In the three cases with mixed pattern, the rhabdoid cells showed more anaplasia and atypism than the conventional meningiomatous elements. In case 3 this was expressed by very high MIB-1 positivity in the rhabdoid cells and absence of same in the fibroblastic meningiomatous elements. These cases (the first three with certainty, the fourth with a strong likelihood) indicate that the phenotypic changes to cells with "rhabdoid" morphology may involve meningiomas and that such change is associated with aggressive biologic and clinical behavior of the tumors showing this type of alteration.

Three-dimensional computerized reconstruction. Illustration of incremental articular cartilage thinning.

RATIONALE AND OBJECTIVES: The authors have addressed the ability of magnetic resonance (MR) imaging to resolve incremental thinning of articular cartilage by assessment of three-dimensional (3-D) and two-dimensional (2-D) representations. METHODS: Using a porcine knee model, sequential cartilage shavings were characterized using a 3-D fat suppressed spoiled gradient-echo (SPGR) MR imaging protocol that provided good contrast between high-signal articular cartilage and lower signal surrounding tissues. Lesion dimensional measurements were made on both MR images and 3-D computerized reconstructions. Volumes of cartilage removed were approximately 0.06 mL. RESULTS: Incremental articular cartilage thinning typically was apparent on 3-D reconstructed images. Three-dimensional articular cartilage reconstructions were effective in depicting location and orientation of shaved cartilage regions. Average percent error associated with length and with measurements based on 2-D MR images was approximately 19% for observer 1 and 33% for observer 2 when compared with direct measurements of the shaved cartilage. Average percent error of thickness measurements based on 2-D MR was approximately 21% for observer 1 and 37% for observer 2. Overall average errors associated with length, width, and thickness measurements were approximately 25%. CONCLUSIONS: Incremental thinning of articular cartilage can be tracked qualitatively and quantitatively using 3-D computerized reconstructions and 2-D MR images. Errors associated with the quantitative measurements can be attributed to limitations of measurement methods and intrinsic limitation of MR resolution.

Analysis of three-dimensional computerized representations of articular cartilage lesions.

RATIONALE AND OBJECTIVES: The authors assess the accuracy of three-dimensional (3D) computer representations based on magnetic resonance images of articular cartilage lesions, using actual cartilage lesions as reference standards. METHODS: Grade 2 and grade 3 articular lesions were created on articular surfaces of five porcine knee joints. The knees were then imaged using 3D fat-suppressed SPGR acquisition at four different slice thicknesses. Magnetic resonance imaging data sets were transferred to a computer workstation for image processing and 3D reconstruction. Lesion dimensions (length, width, and depth) based on the 3D reconstructed image were compared with the dimensions measured using actual lesions. RESULTS: The average percent error of lesion length, width, and depth based on the 3D images ranged from approximately 8% to 12% when using the thinnest magnetic resonance slice thickness (0.7 mm). CONCLUSIONS: Three-dimensional reconstructed images derived from thin-slice magnetic resonance imaging can provide reasonable representations of true articular cartilage lesion dimensions.

Vagal and sciatic nerve stimulation have complex, time-dependent effects on chemically-induced seizures: a controlled study.

Previous studies of the effects of electrical vagus stimulation on experimental seizures were without suitable controls or statistical validation, and ignored the potential role of vagally-induced hemodynamic depression on seizure expression. This study addresses these limitations. The effects of periodic left vagus nerve stimulation (LVNS) on chemically-induced seizures in rats were compared with control groups receiving no stimulation (NoS), left sciatic nerve stimulation (LSNS) and LVNS after pretreatment with methyl atropine (MA-LVNS). Stimulation followed a 30 s on-120 s off cycle over 130 min. Seizures were scored visually and the temporal variation of their probability P(s) across the stimulation cycle was measured statistically. P(s) was significantly different (P<0.01) for all groups: LSNS had the highest and MA-LVNS the lowest seizure probability; LVNS and NoS had intermediate values. While LVNS blocked seizures, it also precipitated them, explaining why its anti-seizure effect was only slightly greater than NoS. Neither LVNS nor MA-LVNS induced changes in cortical rhythms ('activation') associated with decreased P(s), unlike LSNS which increased cortical rhythm synchrony and with it, P(s). LVNS alone induced marked bradycardia and moderate hypoxemia. In conclusion, cranial and peripheral nerve stimulation have complex, time-varying effects on cerebral excitability: low frequency LSNS facilitated seizures, while LVNS both suppressed and facilitated them. The anti-seizure effect of LVNS was small and may have, in part, been due to a hemodynamically-induced deficit in energy substrates. The effects of MA-LVNS on seizure duration and P(s) raise the possibility that, in the absence of hemodynamic depression, stimulation of this nerve does not have a strong anti-seizure effect.

Hematoma in the posterior fossa secondary to a tangential gunshot wound of the occiput: case report and discussion.

The case of 16-year-old boy who incurred a subdural hematoma in the posterior fossa an intracerebellar hematoma after a tangential civilian gunshot wound is reported. The skull was not fractured, and yet surgically significant clots required removal. The patient recovered. The discussion centers on the mechanism of injury and seriousness of tangential gunshot wounds and traumatic hematomas in the posterior fossa.

Magnetic resonance imaging and pathological analysis of a pituicytoma: case report.

A case of a pituicytoma is presented that describes the clinical, pathological, and magnetic resonance imaging features of a rare tumor of the neurohypophysis. A 26-year-old woman presented with a 4-month history of dizziness and visual obscuration. A magnetic resonance image revealed a pituitary mass with suprasellar extension. The specimen obtained from a transsphenoidal decompression identified the mass as an astrocytoma of the posterior pituitary (pituicytoma). Immunohistochemical staining was positive for glial fibrillary acidic protein, S-100, and vimentin. Electron microscopy identified intermediate filaments, numerous broad cell junctions, no secretory granules, and two cellular populations with either an electron-dense or lucent cytoplasmic matrix. This case is unique in that other documented cases originating in the posterior pituitary have all been pilocytic astrocytomas, whereas this neoplasm was not a pilocytic variant. This is also the first case in the literature of a pituicytoma documented by magnetic resonance imaging. This report reviews the cytological elements of the neurohypophysis and the origin of pituicytomas and stresses the proper use of the term "pituicytoma" in relation to tumors of the posterior pituitary.

An introduction to contingent (closed-loop) brain electrical stimulation for seizure blockage, to ultra-short-term clinical trials, and to multidimensional statistical analysis of therapeutic efficacy.

Automated seizure blockage is a top research priority of the American Epilepsy Society. This delivery modality (referred to herein as contingent or closed loop) requires for implementation a seizure detection algorithm for control of delivery of therapy via a suitable device. The authors address the many potential advantages of this modality over conventional alternatives (periodic or continuous), and the challenges it poses in the design and analysis of trials to assess efficacy and safety-in the particular context of direct delivery of electrical stimulation to brain tissue. The experimental designs of closed-loop therapies are currently limited by ethical, technical, medical, and practical considerations. One type of design that has been used successfully in an in-hospital "closed-loop" trial using subjects undergoing epilepsy surgery evaluation as their own controls is discussed in detail. This design performs a two-way comparison of seizure intensity, duration, and extent of spread between the control (surgery evaluation) versus the experimental phase, and, within the experimental phase, between treated versus untreated seizures. The proposed statistical analysis is based on a linear model that accounts for possible circadian effects, changes in treatment protocols, and other important factors such as change in seizure probability. The analysis is illustrated using seizure intensity as one of several possible end points from one of the subjects who participated in this trial. In-hospital ultra-short-term trials to assess safety and efficacy of closed-loop delivery of electrical stimulation for seizure blockage are both feasible and valuable.

Effect and time course of deep brain stimulation of the globus pallidus and subthalamus on motor features of Parkinson's disease.

We studied the effect and temporal profile of deep brain stimulation (DBS) of the globus pallidus and subthalamic nucleus on the motor signs of Parkinson's disease (PD). Four patients with bilateral deep brain stimulators of the globus pallidus and four patients with bilateral deep brain stimulators of the subthalamus were studied while taking no medication and at 15 and 30 minutes and 1, 2, 4, and 6 hours after turning stimulation on. An immediate (15 minutes) and sustained (6 hours) benefit was observed for all the motor manifestations of PD for both stimulation sites. Deep brain stimulation of the globus pallidus and subthalamus is highly effective in reducing all the cardinal motor features of PD.

Cognitive outcome following staged bilateral pallidal stimulation for the treatment of Parkinson's disease.

As neurosurgical treatment of parkinsonian symptoms has become increasingly popular, concern about the cognitive morbidity which may result from such interventions has risen proportionately. Previous reports of cognitive difficulties associated with pallidotomy and thalamotomy, especially in bilateral cases, have provided the impetus for research into chronic electrical deep brain stimulation procedures which are believed to be safer than ablation. Given the lack of neurobehavioral research following bilateral deep brain stimulation procedures, this preliminary study of six Parkinson's disease patients undergoing staged bilateral pallidal stimulation was undertaken. A battery of tests assessing attention, executive function, visuomotor coordination, language, visuoperceptual function, learning memory and mood revealed no significant change in overall level of cognitive functioning after either unilateral or bilateral pallidal deep brain stimulation. No significant declines were observed about three months following bilateral stimulation, and in fact, significant gains in delayed recall and relief of anxiety symptoms were noted. It was concluded from this preliminary data that bilateral pallidal stimulation for the treatment of Parkinson's disease, at least in the absence of operative complications, offers a cognitively safe alternative to ablation.

Synovial cysts of the lumbar spine: diagnosis, surgical management, and pathogenesis. Report of eight cases.

BACKGROUND: Synovial cysts are uncommon extradural degenerative lesions associated with symptoms of lower back pain and radiculopathy. Most of these lesions occur in the lumbar spine at the L4-5 level and to a lesser extent at the L5-S1 and L3-4 levels. METHODS: A retrospective study involving eight patients seen by the neurosurgery service from January 1, 1989, to May 30, 1994, was analyzed. The type, duration, and distribution of symptoms were evaluated, along with the patient's age and sex. All patients had lumbosacral spine x rays and magnetic resonance imaging. Four had a computed tomography-myelogram of the lumbar spine. All patients underwent a laminectomy or hemilaminectomy and cyst excision, and all were followed for a minimum of 1 year. The presence of a synovial cyst was confirmed by histopathology. RESULTS: Of the eight patients, seven had dramatic pain relief with five having complete resolution of pain. The single care of persistent pain was found to be due to scar tissue at the operative site. All five cases of preoperative lower extremity weakness showed complete resolution. Dysesthesia was either unchanged or decreased. CONCLUSIONS: Surgery is a safe, effective treatment for patients with lumbar synovial cysts and is the treatment of choice for these lesions.

Real-time automated detection and quantitative analysis of seizures and short-term prediction of clinical onset.

PURPOSE: We describe an algorithm for rapid real-time detection, quantitation, localization of seizures, and prediction of their clinical onset. METHODS: Advanced digital signal processing techniques used in time-frequency localization, image processing, and identification of time-varying stochastic systems were used to develop the algorithm, which operates in generic or adaptable "modes." The "generic mode" was tested on (a) 125 partial seizures (each contained in a 10-min segment) involving the mesial temporal regions and recorded using depth electrodes from 16 subjects, and (b) 205 ten-minute segments of randomly selected interictal (nonseizure) data. The performance of the algorithm was compared with expert visual analysis, the current "gold standard." RESULTS: The generic algorithm achieved perfect sensitivity and specificity (no false-positive and no false-negative detections) over the entire data set. Seizure intensity, a novel measure that seems clinically relevant, ranged between 35.7 and 6129. Detection was sufficiently rapid to allow prediction of clinical onset in 92% of seizures by a mean of 15.5 s. CONCLUSIONS: This algorithm, which was implemented with a personal computer, represents a definitive step toward rapid and accurate detection and prediction of seizures. It may also enable development of intelligent devices for automated seizure warning and treatment and stimulate new study of the dynamics of seizures and of the epileptic brain.

Textural parameters based on the Spatial Gray Level Dependence Method applied to melanocytic nevi.

The purpose of this study is to evaluate the Spatial Gray Level Dependence Method (SGLDM) of texture analysis with respect to its ability to discriminate between melanocytic nevi and normal skin. Thirteen textural features based on the SGLDM were evaluated with respect to their relative sensitivities to both texture and tone. Ten features were found to be more sensitive to texture than tone and were selected for further study. Twenty-four digitized images of benign melanocytic nevi were obtained from six volunteers. Ten textural features were analyzed for each nevus and for surrounding sections of normal skin. Of these 10 features, 8 features can distinguish between textural properties of melanocytic nevi and surrounding skin.

Chronic electrical stimulation of the left ventrointermediate (Vim) thalamic nucleus for the treatment of pharmacotherapy-resistant Parkinson's disease: a differential impact on access to semantic and episodic memory?

Thalamotomy for medically refractory Parkinson's disease (PD) is considered to be efficacious and relatively safe. Because a minority of patients experience decrements in language and memory (often mild and transient) after thalamotomy, chronic thalamic deep brain stimulation (DBS) might be a safer treatment given its reversibility and the modifiability of stimulation parameters. Two preliminary studies support the relative cognitive safety of unilateral DBS of the ventral intermediate (Vim) thalamic nucleus, but it is unclear whether possibly subtle changes in language and memory represent effects of "microthalamotomy" or of stimulation per se. This report provides preliminary data concerning effects of left thalamic stimulation on information processing speed, semantic memory (verbal fluency and visual confrontation naming), and verbal episodic memory in a patient with PD. In addition to being evaluated before and 3 and 6 months after surgery, the patient was tested 18 months after surgery either on or off medications and with the stimulator turned either on or off (order counterbalanced across medication conditions). Test performance differences between the stimulation conditions were attenuated "off" as compared to "on" medication. Vim stimulation consistently, albeit subtly, improved semantic verbal fluency but interfered with immediate recall of word lists. Parallels to findings from acute, intraoperative thalamic stimulation studies are explored. The hypothesis is offered that left Vim stimulation might facilitate access to semantic memory, but interfere with episodic memory processes.

Long term safety and efficacy of unilateral deep brain stimulation of the thalamus for parkinsonian tremor.

The objective was to investigate the long term safety and efficacy of unilateral deep brain stimulation (DBS) of the VIM nucleus of the thalamus in Parkinson's disease. Twelve patients with Parkinson's disease underwent unilateral DBS of the thalamus for medication resistant tremor between 1994 and 1997. Patients were evaluated with the motor section of the unified Parkinson's disease rating scale (UPDRS) in the medication on state at baseline, 3 months, 12 months, and yearly thereafter.Three patients were lost to follow up. Nine patients had follow up evaluations greater than 24 months and were included in the analyses. The last postsurgical follow up occurred on average 40.0 (SD 17.2) months after surgery. Tremor scores were significantly improved with stimulation on at the long term follow up compared with baseline. There was no significant change in UPDRS motor scores at long term follow up compared with baseline. There was no significant change in any stimulus parameters from 3 months to the long term follow up. Two patients had asymptomatic intracerebral haemorrhages and one patient had a subcutaneous haematoma over the implantable pulse generator site. Stimulus related adverse reactions were mild and easily controlled with changes in stimulus parameters. Two patients had replacement of the implantable pulse generator due to normal battery depletion, one patient had lead repositioning due to migration, and one patient had the lead extension wire replaced due to erosion. In conclusion, unilateral DBS of the thalamus has long term efficacy for treatment of tremor due to Parkinson's disease.