Benedikt syndrome is a rare but debilitating constellation of symptoms that manifests from infarction of the red nucleus, cerebral peduncle, oculomotor fascicles, and lower oculomotor nucleus. Clinically, it presents as ipsilateral cranial nerve III palsy, contralateral hemiataxia with intention tremor, contralateral hemiparesis, and hyperactive tendon reflexes. Commonly, the tremor upon purposeful movement proves to be the most debilitating manifestation of the infarction with significant impact on the patient's ability to perform activities of daily living and, therefore, quality of life. The authors report the successful management of this debilitating post–midbrain infarction tremor with the insertion of a deep brain stimulator with targets in the contralateral lenticular fasciculus.
Deep Brain Stimulation
Deep brain stimulation as an effective treatment option for post–midbrain infarction-related tremor as it presents with Benedikt syndrome
S. Kathleen Bandt, Douglas Anderson, and Jose Biller
Deep brain stimulation in the treatment of obesity
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.
Factors involved in long-term efficacy of deep brain stimulation of the thalamus for essential tremor
Julie G. Pilitsis, Leo Verhagen Metman, John R. Toleikis, Lindsay E. Hughes, Sepehr B. Sani, and Roy A. E. Bakay
Although nucleus ventralis intermedius stimulation has been shown to be safe and efficacious in the treatment of essential tremor, there is a subset of patients who eventually lose benefit from their stimulation. Proposed causes for this phenomenon include tolerance, disease progression, and suboptimal location. The goal of this study was to assess the factors that may lead to both stimulation failure, defined as loss of meaningful tremor relief, and less satisfactory outcomes, defined as leads requiring voltages > 3.6 V for effective tremor control.
The authors present their clinical outcomes from 31 leads in 27 patients who had effective tremor control for > 1 year following nucleus ventralis intermedius stimulation. All patients postoperatively had a mean decrease in both the writing and drawing subscales of the Fahn-Tolosa-Marin Tremor Rating Scale (p < 0.001).
After a mean follow-up of 40 months, 22 patients continued to have tremor control with stimulation. Four patients eventually lost efficacy of their stimulation at a mean of 39 months. There was no difference in age, duration of disease, or disease severity between the groups. Examination of perioperative factors revealed that suboptimal anteroposterior positioning as evidenced on intraoperative fluoroscopy occurred significantly more frequently in patients with stimulation failure (p = 0.018). In patients with less satisfactory outcomes, no difference was seen between group demographics. Fluoroscopy again revealed suboptimal positioning more frequently in these patients (p = 0.005).
This study provides further evidence that suboptimal lead position in combination with disease progression or tolerance may result in less satisfactory long-term outcomes.
A prospective blinded evaluation of deep brain stimulation for the treatment of secondary dystonia and primary torticollis syndromes
Theresa E. Pretto, Arif Dalvi, Un Jung Kang, and Richard D. Penn
The aim of this study was to provide an objective assessment of deep brain stimulation (DBS) for groups of patients with mixed secondary dystonia and primary torticollis syndromes by a blinded evaluation of 13 consecutive patients who underwent ineffective medical treatment and botulinum toxin injections.
Nine patients with secondary dystonia and 4 with cranial dystonia involving prominent spasmodic torticollis were selected for a DBS implant after they underwent unsuccessful medical treatment. Preoperative videos and neurological assessments were obtained and the DBS implant was inserted into the globus pallidus internus. Postoperatively, DBS parameters were adjusted to provide optimal benefit. Postoperative videotapes and quality of life scores were obtained. Blinded randomized evaluation of videotapes was performed by a neurologist specializing in movement disorders. Videos were scored using the Unified Dystonia Rating Scale, Toronto Western Spasmodic Torticollis Rating Scale, Burke-Fahn-Marsden Dystonia Rating Scale, or Abnormal Involuntary Movement Scale. Quality of life scoring was assessed using a standardized 7-point Global Rating Scale.
All 13 patients completed preoperative videotaping, medical assessment, and surgery. Optimal DBS programming was completed in 6.5 visits over 5.9 months. Seven patients reported marked improvement, 3 reported moderate improvement, 2 reported slight improvement or no change, and 1 was lost to follow-up. Examiner scores on the Global Rating Scale reflected patient self-reported scores.
Global subjective gains and notable objective improvement were observed in 11 of 13 patients. Although the benefits were variable and not fully predictable, they were of sufficient magnitude to justify offering the procedure when medications and botulinum toxin injections have failed.
Postmortem analysis following 71 months of deep brain stimulation of the subthalamic nucleus for Parkinson disease
David A. Sun, Hong Yu, John Spooner, Armanda D. Tatsas, Thomas Davis, Ty W. Abel, Chris Kao, and Peter E. Konrad
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective neurosurgical treatment for Parkinson disease. Tissue reaction to chronic DBS therapy and the definitive location of active stimulation contacts are best studied on a postmortem basis in patients who have undergone DBS. The authors report the postmortem analysis of STN DBS following 5 years and 11 months of effective chronic stimulation including the histologically verified location of the active contacts associated with bilateral implants. They also describe tissue response to intraoperative test passes with recording microelectrodes and stimulating semimacroelectrodes. The results indicated that 1) the neural tissue surrounding active and nonactive contacts responds similarly, with a thin glial capsule and foreign-body giant cell reaction surrounding the leads as well as piloid gliosis, hemosiderin-laden macrophages, scattered lymphocytes, and Rosenthal fibers; 2) there was evidence of separate tracts in the adjacent tissue for intraoperative microelectrode and semimacroelectrode passes together with reactive gliosis, microcystic degeneration, and scattered hemosiderin deposition; and 3) the active contacts used for ~ 6 years of effective bilateral DBS therapy lie in the zona incerta, just dorsal to the rostral STN. To the authors' knowledge, the period of STN DBS therapy herein described for Parkinson disease and subjected to postmortem analysis is the longest to date.
Subthalamic deep brain stimulation after anesthetic inhalation in Parkinson disease: a preliminary study
Sheng-Huang Lin, Tsung-Ying Chen, Shinn-Zong Lin, Ming-Hwang Shyr, Yu-Cheng Chou, Wanhua Annie Hsieh, Sheng-Tzung Tsai, and Shin-Yuan Chen
The authors of this preliminary study investigated the outcome and feasibility of intraoperative microelectrode recording (MER) in patients with Parkinson disease (PD) undergoing deep brain stimulation of the subthalamic nucleus (STN) after anesthetic inhalation.
The authors conducted a retrospective analysis of 10 patients with PD who received a desflurane anesthetic during bilateral STN electrode implantation. The MERs were obtained as an intraoperative guide for final electrode implantation and the data were analyzed offline. The functional target coordinates of the electrodes were compared preoperatively with estimated target coordinates.
Outcomes were evaluated using the Unified Parkinson's Disease Rating Scale 6 months after surgery. The mean improvement in total and motor Unified Parkinson's Disease Rating Scale scores was 54.27 ± 17.96% and 48.85 ± 16.97%, respectively. The mean STN neuronal firing rate was 29.7 ± 14.6 Hz. Typical neuronal firing patterns of the STN and substantia pars nigra reticulata were observed in each patient during surgery. Comparing the functional target coordinates, the z axis coordinates were noted to be significantly different between the pre- and postoperative coordinates.
The authors found that MER can be adequately performed while the patient receives a desflurane anesthetic, and the results can serve as a guide for STN electrode implantation. This may be a good alternative surgical method in patients with PD who are unable to tolerate deep brain stimulation surgery with local anesthesia.
Long-term follow-up of Huntington disease treated by bilateral deep brain stimulation of the internal globus pallidus
Brigitte Biolsi, Laura Cif, Hassan El Fertit, Santiago Gil Robles, and Philippe Coubes
Deep brain stimulation is now accepted as a safe and efficient treatment for movement disorders including selected types of dystonia and dyskinesia. Very little, however, is known about its effect on other movement disorders, particularly for “choreic” movements. Huntington disease is a fatal autosomal-dominant neurodegenerative disorder characterized by movement disorders, progressive cognitive impairment, and psychiatric symptoms. Bilateral chronic stimulation of the internal globus pallidus was performed to control choreic movements in a 60-year-old man with a 10-year history of Huntington disease. Chronic deep brain stimulation resulted in remarkable improvement of choreic movements. Postoperative improvement was sustained after 4 years of follow-up with a marked improvement in daily quality of life.
Motor cortex stimulation in patients with Parkinson disease: 12-month follow-up in 4 patients
Jeffrey E. Arle, Diana Apetauerova, Janet Zani, D. Vedran Deletis, Dana L. Penney, Daniel Hoit, Christine Gould, and Jay L. Shils
Since the initial 1991 report by Tsubokawa et al., stimulation of the M1 region of cortex has been used to treat chronic pain conditions and a variety of movement disorders.
A Medline search of the literature published between 1991 and the beginning of 2007 revealed 459 cases in which motor cortex stimulation (MCS) was used. Of these, 72 were related to a movement disorder. More recently, up to 16 patients specifically with Parkinson disease were treated with MCS, and a variety of results were reported. In this report the authors describe 4 patients who were treated with extradural MCS.
Although there were benefits seen within the first 6 months in Unified Parkinson's Disease Rating Scale Part III scores (decreased by 60%), tremor was only modestly managed with MCS in this group, and most benefits seen initially were lost by the end of 12 months.
Although there have been some positive findings using MCS for Parkinson disease, a larger study may be needed to better determine if it should be pursued as an alternative surgical treatment to DBS.
Direct inhibition of levodopa-induced beginning-of-dose motor deterioration by subthalamic nucleus stimulation in a patient with Parkinson disease
Hideki Oshima, Yoichi Katayama, Chikashi Fukaya, Toshikazu Kano, Kazutaka Kobayashi, Takamitsu Yamamoto, and Yutaka Suzuki
✓Beginning-of-dose motor deterioration (BDMD) is a complication of levodopa medications in Parkinson disease (PD) that is presumably caused by inhibitory effects of levodopa. Only limited experience of BDMD has been described in the literature. The authors report the case of a patient with PD who demonstrated a marked BDMD while being treated with standard levodopa medications. This 55-year-old woman had a 12-year history of PD and a 10-year history of levodopa treatment. Marked exacerbation of symptoms occurred 15 to 20 minutes after every dose of levodopa at 100 mg and lasted approximately 15 minutes. The PD symptoms, particularly tremor and rigidity, were exacerbated more markedly during this period than during the wearing-off deterioration. The BDMD could be controlled very well by subthalamic nucleus (STN) stimulation without any change in the regimen of levodopa medications. These observations suggest that the BDMD was inhibited by STN stimulation through a direct effect.
The regulation of adult rodent hippocampal neurogenesis by deep brain stimulation
Hiroki Toda, Clement Hamani, Adrian P. Fawcett, William D. Hutchison, and Andres M. Lozano
To examine the influence of deep brain stimulation on hippocampal neurogenesis in an adult rodent model.
Rats were anesthetized and treated for 1 hour with electrical stimulation of the anterior nucleus of the thalamus (AN) or sham surgery. The animals were injected with 5′-bromo-2′-deoxyuridine (BrdU) 1–7 days after surgery and killed 24 hours or 28 days later. The authors counted the BrdU-positive cells in the dentate gyrus (DG) of the hippocampus. To investigate the fate of these cells, they also stained sections for doublecortin, NeuN, and GFAP and analyzed the results with confocal microscopy. In a second set of experiments they assessed the number of DG BrdU-positive cells in animals treated with corticosterone (a known suppressor of hippocampal neurogenesis) and sham surgery, corticosterone and AN stimulation, or vehicle and sham surgery.
Animals receiving AN high-frequency stimulation (2.5 V, 90 μsec, 130 Hz) had a 2- to 3-fold increase in the number of DG BrdU-positive cells compared with nonstimulated controls. This increase was not seen with stimulation at 10 Hz. Most BrdU-positive cells assumed a neuronal cell fate. As expected, treatment with corticosterone significantly reduced the number of DG BrdU-positive cells. This steroid-induced reduction of neurogenesis was reversed by AN stimulation.
High-frequency stimulation of the AN increases the hippocampal neurogenesis and restores experimentally suppressed neurogenesis. Interventions that increase hippocampal neurogenesis have been associated with enhanced behavioral performance. In this context, it may be possible to use electrical stimulation to treat conditions associated with impairment of hippocampal function.