Robotic Deep Brain Stimulation (R-DBS)-"Awake" Deep Brain Stimulation Using the Neuromate Robot and O-Arm.

BACKGROUND: Deep brain stimulation (DBS) is an effective surgical technique used to ameliorate the motor symptoms associated with Parkinson's disease. One of the key elements that determine successful patient outcomes is the accurate positioning of the DBS electrode during surgery. OBJECTIVE: To describe a robotic DBS (R-DBS) procedure using "awake" technique. METHODS AND MATERIALS: This procedure was performed using a frame-based approach with the NeuroMate surgical robot and intraoperative image verification of DBS electrode placement using the O-arm mobile x-ray system. The procedure was performed "Awake" using microelectrode recording (MER), stimulation, and macro-electrode testing. RESULTS: The accurate placement of DBS electrodes was confirmed with intraoperative image verification. This patient had good therapeutic response intraoperatively. No immediate postoperative complications related to DBS electrode placement were identified. CONCLUSIONS: R-DBS is a technique that can be used for the highly accurate placement of electrodes necessary for DBS.

Single injection of a low dose of pentylenetetrazole leads to epileptogenesis in an animal model of cortical dysplasia.

PURPOSE: Cortical dysplasia (CD) is one of the most frequent causes of pharmacoresistent focal epilepsy. Despite significant advances in various diagnostic and therapeutic methods, the basic mechanisms of higher susceptibility for seizures in patients with CD are unknown. Animal models of CD present with a lower threshold for seizure induction. The purpose of this study is to further characterize the animal model of in utero radiation-induced CD and to illustrate the effect of a late postnatal second hit (low dose of pentylenetetrazole, PTZ) on the development of spontaneous seizures. METHODS: Pregnant Sprague-Dawley rats were irradiated on E17 (145 cGy; control group was left untreated). Litters were implanted with bifrontal epidural and hippocampal depth electrodes. After baseline electroencephalography (EEG) recording, animals received 30 mg/kg PTZ and were chronically monitored. Histopathology of the brains was verified. RESULTS: No seizures were detected in animals that did not receive PTZ. PTZ-injected irradiated (XRT) rats showed severe prolonged, repetitive seizures during the acute period. During the chronic period, XRT rats had recurrent seizures and epileptiform spikes. PTZ-injected control animals exhibited milder and fewer acute seizures and did not show seizures during the chronic period. Histology was consistent with cortical and hippocampal dysplasia. CONCLUSIONS: This study shows that a single treatment with a low dose of PTZ renders XRT rats (but not age-matched controls) epileptic, exhibiting spontaneous epileptiform spikes and seizures on EEG. These results might mirror the natural history of patients with CD thought to be caused by prenatal/congenital or perinatal insults.

Gene expression changes in an animal model of in utero irradiation-induced Cortical Dysplasia.

PURPOSE: Cortical Dysplasia (CD) is the histopathological substrate in almost half of all drug-resistant focal epilepsies. Little is known about the gene expression profile of CD. As such information may help target therapeutics more effectively, our aim was to perform a gene expression analysis of an animal model of cortical dysplasia induced by in utero irradiation. METHODS: Nine offspring from irradiated animals, and nine age-matched controls were sacrificed at post-natal day 60. Cortical and hippocampal regions were separated, and total ribonucleic acid (RNA) was extracted using a commercially available kit (Qiagen). RNA was then subjected to a gene expression analysis using an oligonucleotide microarray platform (Illumina). After statistical analysis, genes were considered differentially expressed when a p value less than 0.001 was observed. Real-time, quantitative polymerase chain reaction (RT-qPCR) was used to confirm microarray results for three genes via the Livak method. RESULTS: Twenty three genes from cortical tissue met criteria for altered gene expression. Six genes from cortex seemed relevant to the pathogenesis of CD. Two genes that promoted cell survival (connective tissue growth factor and peroxiredoxin) were upregulated. One gene that promoted excitotoxic neurodegeneration (latrophilin-2) was downregulated. Two genes involved in glutamate (protein kinase C-alpha) and AMPA receptor recycling (NEEP-21) were downregulated. One gene, (Shank-1) involved in the control of dendritic maturation, was downregulated. CONCLUSION: Gene expression analysis in this animal model revealed some of the potential mechanisms by which CD may lead to the phenotype of intractable epilepsy. The downregulation of genes that are involved in glutamate and AMPA receptor recycling may lead to increased excitability. Disinhibition of aberrant dendritic branching, resulting from a downregulation of Shank-1, may also result in an increase in sprouting, excitation and/or hypersynchrony. Finally, genes promoting cell survival, either directly (connective tissue growth factor, peroxiredoxin) or indirectly (latrophilin-2) may allow CD tissue to survive the excitotoxic injury that it produces, thus allowing it to perpetuate the epileptic condition over time.

Oligoastrocytoma presenting with intractable epilepsy.

OBJECTIVE: Oligoastrocytomas (OA) are mixed gliomas with distinct oligodendroglial and astrocytic neoplastic components. Very little about OA has been reported in the intractable epilepsy population. METHODS: We undertook a retrospective review of 923 patients who underwent resective surgery for intractable epilepsy between 1996 and 2004. RESULTS: 6/923 (0.7%) patients were diagnosed with OA. Five patients were female, one was male. Median age at diagnosis was 25 years (range 19-44 years). Tumors arose from the left side in all patients and from the temporal lobe in five patients. Three patients had complex partial seizures. Median length of refractory epilepsy prior to surgery was 10.5 years (range 1-28 years), and the median number of antiepileptic drugs used was 2 (range 1-10). Preoperative WADA testing for language and memory localization was done for three patients; preoperative stereotactical localization was done for three patients. Surgical pathology revealed low-grade OA (WHO II) in five patients, and anaplastic OA in one. There were no surgical complications, clinical or radiographic tumor recurrence at a mean follow up period of 3.2 years (range 2-8). Excellent seizure freedom was achieved in 5/6 patients. CONCLUSION: As a result of our small sample size, general conclusions may be imprecise, but this review suggests that OA behave similar to other tumors related to intractable epilepsy: they usually have a preoperative seizure course of many years, an excellent rate of seizure-freedom following surgery, and are in general, low-grade tumors with an indolent course for which serial imaging is sufficient follow-up.

Risk factors for carbamazepine elevation and toxicity following epilepsy surgery.

UNLABELLED: A proportion of patients undergoing epilepsy surgery, and receiving carbamazepine (CBZ), experience significant elevations in CBZ plasma concentrations, some with associated CBZ toxicity. The objective of this study was to identify significant risk factors for elevations (>12 microg/ml) in CBZ concentrations and CBZ-induced toxicity following epilepsy surgery. METHODS: We retrospectively examined charts of 74 inpatients (31 children and 43 adults) chronically receiving CBZ and undergoing epilepsy surgery between January 1996 and June 2000. Patient demographics, medications, type of surgery, seizure history, adverse events, CBZ doses and concentrations were evaluated. RESULTS: 51.2% of adults and 51.6% of pediatric patients had drug elevations. In the pediatric group, 12.9% had symptoms of toxicity compared to 9.3% in the adult group. Five risk factors-pre-operative CBZ dose, fentanyl dose, surgery day CBZ concentration, body weight, and blood loss-were related to post-operative CBZ concentrations. Three risk factors: age <18 years, pre-operative CBZ dose, and the surgery day CBZ (immediate pre-operative) concentration, were significantly related to the outcome measure of abnormal CBZ concentration (>12 microg/ml). Two variables significantly related to toxicity were average post-operative CBZ dose and the surgery day CBZ concentration. Increases in concentrations occurred at a mean 33+/-13.7 h (range: 11-74 h) after surgery. DISCUSSION: Based upon our results in patients with one or more risk factors, we suggest that reduction of post-operative CBZ doses be considered.

Quality-of-life outcomes with minimally invasive transforaminal lumbar interbody fusion based on long-term analysis of 304 consecutive patients.

STUDY DESIGN: This was a prospective clinical study that took place in an outpatient spine clinic. OBJECTIVE: To demonstrate the short-/long-term outcomes from a large cohort of patients undergoing minimally invasive transforaminal lumbar interbody fusion (MITLIF). SUMMARY OF BACKGROUND DATA: Long-term prospective outcomes in patients undergoing minimally invasive spinal fusion for debilitating back pain has not been well studied. METHODS: Presenting diagnosis was determined from clinical findings and radiographical (radiograph, magnetic resonance image, computed tomographic scan) evaluations preoperatively. Patients were assessed with outcome measures preoperatively, and postoperatively at 2 weeks, 3 months, 6 months, 12 months, 24 months, and annually 2 to 7 years (mean follow-up: 47 mo) final follow-up. The rate of postoperative complications and reoperations at the initial level of MITLIF and adjacent level(s) were followed. Fusion rates were assessed blinded and independently by radiograph. RESULTS: Visual analogue scale scores decreased significantly from 7.0 preoperatively to 3.5 at mean 47-month follow-up. Oswestry Disability Index scores declined from 43.1 preoperatively to 28.2 at mean 47-month follow-up. Short-Form 36 mental component scores increased from 43.8 preoperatively to 49.7 at 47-month follow-up. Short-Form 36 physical component scores increased from 30.6 preoperatively to 39.6 at 47-month follow-up (P < 0.05). CONCLUSION: This prospectively collected outcomes study shows long-term statistically significant clinical outcomes improvement after MITLIF in patients with clinically symptomatic spondylolisthesis and degenerative disc disease with or without stenosis. MITLIF resulted in a high rate of spinal fusion and very low rate of interbody fusion failure and/or adjacent segment disease requiring reoperation while reducing postoperative complications. LEVEL OF EVIDENCE: 3.

Predicting seizure freedom after two or more chronic invasive evaluations in patients with intractable epilepsy.

OBJECTIVE: In patients with intractable epilepsy, failure to localize and/or resect the epileptic focus after invasive monitoring is multifactorial. Rarely do these patients return for a second invasive evaluation, and their outcome is not clearly characterized. This study aims to determine the seizure outcome after a second invasive electroencephalographic (EEG) evaluation, and its possible predictors. METHODS: We retrospectively reviewed 30 patients who underwent two or more invasive evaluations at Cleveland Clinic between 1980 and 2007. Clinical, surgical, imaging, and pathology information was analyzed using a multivariate regression model. A favorable outcome was defined as complete seizure freedom, allowing for auras and seizures restricted to the first postoperative week. RESULTS: Ten patients (33%) became seizure free after the second operation (mean follow-up duration 3.13 years [range 6 months-17 years]). Seizure freedom was more likely in patients reporting fewer seizures per month preoperatively (mean 19 seizures/mo), and in those with a predominantly regional/lateralized scalp EEG ictal pattern (32% seizure free), as opposed to those with higher seizure frequency (mean 70 seizures/month; P = 0.02) or diffuse ictal EEGs (0% seizure free; P = 0.04). There was a significant association between acute postoperative seizures and failure of repeat surgery (P = 0.0083). In 17 of 30 patients, at least one complication was reported (57%) after the second invasive evaluation compared with a complication rate of 23% after the first invasive evaluation. CONCLUSIONS: A second invasive evaluation may lead to seizure freedom in one-third of patients. However, this must be weighed against the increased complication rate with reoperation.

Is it safe to use recombinant human bone morphogenetic protein in posterior cervical fusion?

STUDY DESIGN: A retrospective chart review of all patients who underwent posterior cervical fusion during a 1-year time period. OBJECTIVE: To analyze the safety profile of recombinant human bone morphogenetic protein (rhBMP)-2 in posterior cervical fusion. SUMMARY OF BACKGROUND DATA: Use of rhBMP-2 in anterior cervical spine surgery has been associated with complications including postoperative edema, dysphagia, and hematoma formation. No literature exists regarding the safety of rhBMP-2 use for posterior cervical fusion. METHODS: We reviewed all posterior cervical fusions performed during 1 year at our hospital following institutional review board permission. RESULTS: A total of 83 patients underwent posterior cervical fusion. Sixty-seven (81%) did not receive rhBMP (control group), whereas 16 (19%) underwent fusion with rhBMP. The most common reason for the use of rhBMP was a failure of an anterior cervical fusion resulting in persistent neck pain, myelopathy, or radiculopathy. The average dose of rhBMP used was 1.3 mL per level. Immediate postoperative medical complications occurred in 5 (7%) in the control group and 2 (13%) in the rhBMP group. A new neurologic deficit after surgery was found in 3 (4%) in the control group and 1 (6%) in the rhBMP group. Wound infection requiring further surgery occurred in 8 (12%) in the control group, and in none in the rhBMP group. One (6%) patient in the rhBMP group had significant postoperative neck swelling, but improved with steroid treatment over 1 week, and without any compromise of vital neck structures. No postoperative hematomas were seen in either group. Chi2 analysis revealed that no complication variable reached significance (P < 0.05) when the 2 groups were compared. CONCLUSION: rhBMP can safely be used in patients undergoing posterior cervical fusion, as it does not produce complications at the rate previously seen with its use in the anterior cervical spine.

Magnetic resonance spectroscopy in animal models of epilepsy.

The noninvasive localization of the epileptogenic zone continues to be a challenge in many patients that present as candidates for possible epilepsy surgery. Magnetic resonance imaging (MRI) techniques provide accurate anatomical definition, but despite their high resolution, these techniques fail to visualize the pathological neocortical and hippocampal changes in a sizable number of patients with focal pathologies. Further, visualized lesions on MRI may not all produce seizures. One of the keys to the understanding of the epileptogenic zone lies in the recognition of the metabolic alterations that occur in the setting of epileptic seizures. Magnetic resonance spectroscopy (MRS) is a valuable tool that can be used to study the metabolic changes seen in both acute and chronic animal models of epilepsy. Such study allows for the identification of epileptic tissue with high sensitivity and specificity. We present here a review of the use of MRS in animal models of epilepsy.

Fracture of subthalamic nucleus deep brain stimulation hardware as a result of compulsive manipulation: case report.

OBJECTIVE AND IMPORTANCE: Trichotillomania (TTM) is an impulse control disorder characterized by the recurrent pulling of one's hair resulting in noticeable hair loss. There has been no definite association drawn between Parkinson's disease (PD) and TTM, although there is a suggestion that obsessive-compulsive symptomatology may be more prevalent in left-side predominant PD. We believe that it is important to be aware of psychiatric comorbidities in the surgical treatment of PD, as they may significantly impact the postoperative course. CLINICAL PRESENTATION: We describe the case of a 58-year-old woman with an eleven-year history of left-side predominant PD who also suffered from TTM. She underwent subthalamic nucleus deep brain stimulation (STN-DBS) and subsequently developed significant wound complications of her left-sided deep brain stimulation leads. It was noted during the postoperative period that the patient was picking her left-sided, but not right-sided, incision-a behavior that was felt to be a part of this patient's impulse control disorder. INTERVENTION: Multiple wound revisions and eventual replacement of her left-sided deep brain stimulation lead was performed as a result of hardware malfunction secondary to wound manipulation by the patient. CONCLUSION: Before surgery, this patient's TTM was right-sided, but after subthalamic nucleus deep brain stimulation, her wound picking was only left-sided. This case suggests that subthalamic nucleus deep brain stimulation may have a role in unleashing the symptomatology of TTM through an as yet poorly understood mechanism. Furthermore, there is also an implication that the pathophysiology of PD and TTM may be intertwined.