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Walter D. Obrist, Thomas W. Langfitt, Jurg L. Jaggi, Julio Cruz and Thomas A. Gennarelli

✓ Cerebral blood flow (CBF) measurements were made in 75 adult patients with closed head injuries (mean Glasgow Coma Scale score 6.2), using the xenon-133 intravenous injection method with eight detectors over each hemisphere. All patients were studied acutely within 96 hours of trauma, and repeatedly observed until death or recovery (total of 361 examinations). Arteriojugular venous oxygen differences (AVDO2) were obtained in 55 of the patients, which permitted assessment of the balance between metabolism and blood flow, and provided estimates of cerebral metabolic rate for oxygen (CMRO2).

Based on mean regional CBF, the patients were classified into two groups: those who exhibited hyperemia on one or more examinations, and those who had a consistently reduced flow during their acute illness. “Hyperemia” was defined as a normal or supernormal CBF in the presence of coma, a definition that was independently confirmed by narrow AVDO2's indicative of “luxury perfusion.” During coma, all patients showed a significant depression in CMRO2.

Forty-one patients (55%) developed an acute hyperemia with an average duration of 3 days, while 34 patients (45%) consistently had subnormal flows. Although more prevalent in younger patients, hyperemia was found at all age levels (15 to 85 years). There was a highly significant association between hyperemia and the occurrence of intracranial hypertension, defined as an intracranial pressure above 20 mm Hg. Patients with reduced flow showed little or no evidence of global cerebral ischemia, but instead revealed the expected coupling of CBF and metabolism. The CBF responses to hyperventilation were generally preserved, with the hyperemic patients being slightly more reactive. In 10 patients with reduced flow, hyperventilation resulted in wide AVDO2's suggestive of ischemia.

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Jurg L. Jaggi, Walter D. Obrist, Thomas A. Gennarelli and Thomas W. Langfitt

✓ Cerebral blood flow (CBF) measurements were obtained acutely in 96 comatose patients with closed head injury, using the intravenous 133Xe technique. Arteriojugular venous oxygen differences and cerebral metabolic rate for oxygen (CMRO2) were determined in a subgroup of 66 patients. The relationship between each of these variables and outcome at 6 months was analyzed, using the Glasgow Outcome Scale.

The CMRO2 was significantly depressed in patients who subsequently died or remained in a vegetative state, whereas higher values were obtained in patients who later regained consciousness. Although CBF was not predictive of outcome in the total sample, omission of patients with acute hyperemia resulted in a significant relationship that paralleled the metabolic findings. Follow-up studies in the survivors revealed a correlation between CBF and degree of functional recovery, the lowest blood flows being obtained among patients with severe disability.

Age, initial Glasgow Coma Scale score, and occurrence of intracranial hypertension were each found to be predictive of outcome, thus confirming previous reports. When these variables were combined with CMRO2 in a logistic regression analysis, the probability of recovery was correctly predicted in 82% of the cases. The CMRO2 was relatively independent of the other prognostic indicators and, next to age, contributed most to the prediction.

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Jason M. Schwalb, Howard A. Riina, Brett Skolnick, Jurg L. Jaggi, Tanya Simuni and Gordon H. Baltuch

✓ The treatment of essential tremor with thalamic deep brain stimulation (DBS) is considered to be more effective and to cause less morbidity than treatment with thalamotomy. Nonetheless, implantation of an indwelling electrode, connectors, and a generator is associated with specific types of morbidity. The authors describe three patients who required revision of their DBS systems due to lead breakage. The connector between the DBS electrode and the extension wire, which connects to the subclavicular pulse generator, was originally placed subcutaneously in the cervical region to decrease the risk of erosion through the scalp and to improve cosmesis. Three patients presented with fractured DBS electrodes that were located in the cervical region near the connector, necessitating reoperation with stereotactic retargeting and placement of a new intracranial electrode. At reoperation, the connectors were placed subgaleally over the parietal region.

Management of these cases has led to modifications in the operative procedure designed to improve the durability of DBS systems. The authors recommend that surgeons avoid placing the connection between the DBS electrode and the extension wire in the cervical region because patient movement can cause microfractures in the electrode. Such microfractures require intracranial revision, which may be associated with a higher risk of morbidity than the initial operation. The authors also recommend considering prophylactic relocation of the connectors from the cervical area to the subgaleal parietal region to decrease the risk of future DBS electrode fracture, which would necessitate a more lengthy procedure to revise the intracranial electrode.

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Tanya Simuni, Jurg L. Jaggi, Heather Mulholland, Howard I. Hurtig, Amy Colcher, Andrew D. Siderowf, Bernard Ravina, Brett E. Skolnick, Reid Goldstein, Matthew B. Stern and Gordon H. Baltuch

Object. Palliative neurosurgery has reemerged as a valid therapy for patients with advanced Parkinson disease (PD) that is complicated by severe motor fluctuations. Despite great enthusiasm for long-term deep brain stimulation (DBS) of the subthalamic nucleus (STN), existing reports on this treatment are limited. The present study was designed to investigate the safety and efficacy of bilateral stimulation of the STN for the treatment of PD.

Methods. In 12 patients with severe PD, electrodes were stereotactically implanted into the STN with the assistance of electrophysiological conformation of the target location. All patients were evaluated preoperatively during both medication-off and -on conditions, as well as postoperatively at 3, 6, and 12 months during medication-on and -off states and stimulation-on and -off conditions. Tests included assessments based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests.

The stimulation effect was significant in patients who were in the medication-off state, resulting in a 47% improvement in the UPDRS Part III (Motor Examination) score at 12 months, compared with preoperative status. The benefit was stable for the duration of the follow-up period. Stimulation produced no additional benefit during the medication-on state, however, when compared with patient preoperative status. Significant improvements were made in reducing dyskinesias, fluctuations, and duration of off periods.

Conclusions. This study demonstrates that DBS of the STN is an effective treatment for patients with advanced, medication-refractory PD. Deep brain stimulation of the STN produced robust improvements in motor performance in these severely disabled patients while they were in the medication-off state. Serious adverse events were common in this cohort; however, only two patients suffered permanent sequelae.

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Atsushi Umemura, Jurg L. Jaggi, Howard I. Hurtig, Andrew D. Siderowf, Amy Colcher, Matthew B. Stern and Gordon H. Baltuch

Object. Deep brain stimulation (DBS) has been advocated as a more highly effective and less morbidity-producing alternative to ablative stereotactic surgery in the treatment of medically intractable movement disorders. Nevertheless, the exact incidence of morbidity and mortality associated with the procedure is not well known. In this study the authors reviewed the surgical morbidity and mortality rates in a large series of DBS operations.

Methods. The authors retrospectively analyzed surgical complications in their consecutive series of 179 DBS implantations in 109 patients performed by a single surgical team at one center between July 1998 and April 2002. The mean follow-up period was 20 months.

There were 16 serious adverse events related to surgery in 14 patients (12.8%). There were two perioperative deaths (1.8%), one caused by pulmonary embolism and the second due to aspiration pneumonia. The other adverse events were two pulmonary embolisms, two subcortical hemorrhages, two chronic subdural hematomas, one venous infarction, one seizure, four infections, one cerebrospinal fluid leak, and one skin erosion. The incidence of permanent sequelae was 4.6% (five of 109 patients). The incidence of device-related complications, such as infection or skin erosion, was also 4.6% (five of 109 patients).

Conclusions. There is a significant incidence of adverse events associated with the DBS procedure. Nevertheless, DBS is clinically effective in well-selected patients and should be seriously considered as a treatment option for patients with medically refractory movement disorders.

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Uzma Samadani, Atsushi Umemura, Jurg L. Jaggi, Amy Colcher, Eric L. Zager and Gordon H. Baltuch

✓ Thalamic deep brain stimulation (DBS) has been demonstrated to be effective for the treatment of parkinsonian or essential tremor. To date, however, few data exist to support the application of this method to treat midbrain tremor.

A 24-year-old right-handed man underwent radiosurgery and subsequent resection of a recurrently hemorrhaging cavernous angioma located in the left side of the midbrain. The surgery exacerbated severe choreoathetotic resting and action tremors of his right extremities and trunk. The patient underwent placement of a deep brain stimulator into the left ventral intermediate nucleus of the thalamus (Vim). Postoperatively, decreased truncal ataxia and right-sided choreoathetotic tremor were demonstrated, with a 57% increase in dexterity as measured by task testing.

The authors demonstrate that DBS can be an effective treatment modality for disabling tremor after resection of a midbrain cavernous angioma.

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Atsushi Umemura, Jurg L. Jaggi, Carol A. Dolinskas, Matthew B. Stern and Gordon H. Baltuch

✓ Generalized dystonia is one of the most disabling movement disorders. Ablative stereotactic surgery such as pallidotomy has been performed for medically refractory dystonia. Recently, deep brain stimulation (DBS) has appeared as an alternative to ablative procedures. Nevertheless, there have been few published reports detailing improvement in dystonia with DBS.

This 36-year-old man with Hallervorden—Spatz syndrome suffered from intractable primary generalized dystonia for 28 years. He was completely dependent for activities of daily living and wheelchair bound because of continuous severe dystonic movements in the face, tongue, neck, trunk, and upper and lower extremities while at rest. The Burke-Fahn-Marsden (BFM) Dystonia Rating Scale score was 112 (maximum 120 points). Bilateral DBS of the globus pallidus internus was performed and resulted in marked improvement in motor functioning and dystonic symptoms with a significant reduction in disability. The BFM score improved to 22.5 points (80% improvement) at 3 months postsurgery and the patient's dystonia was still well suppressed 1 year after surgery.

Bilateral pallidal stimulation is an effective and safe treatment for intractable generalized dystonia in Hallervorden—Spatz syndrome, even if the disability is severe and longstanding.

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Galit Kleiner-Fisman, Grace S. Lin Liang, Paul J. Moberg, Anthony C. Ruocco, Howard I. Hurtig, Gordon H. Baltuch, Jurg L. Jaggi and Matthew B. Stern

Object

Medically refractory dystonia has recently been treated using deep brain stimulation (DBS) targeting the globus pallidus internus (GPI). Outcomes have varied depending on the features of the dystonia. There has been limited literature regarding outcomes for refractory dystonia following DBS of the subthalamic nucleus (STN).

Methods

Four patients with medically refractory, predominantly cervical dystonia underwent STN DBS. Intraoperative assessments with the patients in a state of general anesthesia were performed to determine the extent of fixed deformities that might predict outcome. Patients were rated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) preoperatively and 3 and 12 months following surgery by a rater blinded to the study. Mean changes and standard errors of the mean in scores were calculated for each subscore of the two scales. Scores were also analyzed using analysis of variance and probability values were generated. Neuropsychological assessments and quality of life ratings using the 36-Item Short Form Health Survey (SF-36) were evaluated longitudinally.

Results

Significant improvements were seen in motor (p = 0.04), disability (p = 0.02), and total TWSTRS scores (p = 0.03). Better outcomes were seen in those patients who did not have fixed deformities. There was marked improvement in the mental component score of the SF-36. Neuropsychological function was not definitively impacted as a result of the surgery.

Conclusions

Deep brain stimulation of the STN is a novel target for dystonia and may be an alternative to GPI DBS. Further studies need to be performed to confirm these conclusions and to determine optimal candidates and stimulation parameters.

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Casey H. Halpern, John A. Wolf, Tracy L. Bale, Albert J. Stunkard, Shabbar F. Danish, Murray Grossman, Jurg L. Jaggi, M. Sean Grady and Gordon H. Baltuch

Obesity is a growing global health problem frequently intractable to current treatment options. Recent evidence suggests that deep brain stimulation (DBS) may be effective and safe in the management of various, refractory neuropsychiatric disorders, including obesity. The authors review the literature implicating various neural regions in the pathophysiology of obesity, as well as the evidence supporting these regions as targets for DBS, in order to explore the therapeutic promise of DBS in obesity.

The lateral hypothalamus and ventromedial hypothalamus are the appetite and satiety centers in the brain, respectively. Substantial data support targeting these regions with DBS for the purpose of appetite suppression and weight loss. However, reward sensation associated with highly caloric food has been implicated in overconsumption as well as obesity, and may in part explain the failure rates of conservative management and bariatric surgery. Thus, regions of the brain's reward circuitry, such as the nucleus accumbens, are promising alternatives for DBS in obesity control.

The authors conclude that deep brain stimulation should be strongly considered as a promising therapeutic option for patients suffering from refractory obesity.

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Daniel R. Kramer, Casey H. Halpern, Dana L. Buonacore, Kathryn R. McGill, Howard I. Hurtig, Jurg L. Jaggi and Gordon H. Baltuch

Deep brain stimulation (DBS) is the treatment of choice for otherwise healthy patients with advanced Parkinson disease who are suffering from disabling dyskinesias and motor fluctuations related to dopaminergic therapy. As DBS is an elective procedure, it is essential to minimize the risk of morbidity. Further, precision in targeting deep brain structures is critical to optimize efficacy in controlling motor features. The authors have already established an operational checklist in an effort to minimize errors made during DBS surgery. Here, they set out to standardize a strict, step-by-step approach to the DBS surgery used at their institution, including preoperative evaluation, the day of surgery, and the postoperative course. They provide careful instruction on Leksell frame assembly and placement as well as the determination of indirect coordinates derived from MR images used to target deep brain structures. Detailed descriptions of the operative procedure are provided, outlining placement of the stereotactic arc as well as determination of the appropriate bur hole location, lead placement using electrophysiology, and placement of the internal pulse generator. The authors also include their approach to preventing postoperative morbidity. They believe that a strategic, step-by-step approach to DBS surgery combined with a standardized checklist will help to minimize operating room mistakes that can compromise targeting and increase the risk of complication.