Five-months-postoperative neuropsychological outcome from a pilot prospective randomized clinical trial of thalamic deep brain stimulation for Tourette syndrome.

OBJECTIVE: Tourette syndrome (TS) is a neuropsychiatric disorder presenting with motor and/or sonic tics associated with frontostriatal dysfunction. This study provided pilot data of the neuropsychological safety of bilateral thalamic deep brain stimulation (DBS) to treat medication-refractory TS in adults. METHOD: This study used a repeated-measures design with pretest and 3-month follow-up from start of continuous bilateral DBS. Five male patients underwent DBS surgery for medically refractory TS. Repeated-measures ANOVA was used to evaluate for any change in neuropsychological test scores, employing a false discovery rate. Outcome measures included 14 neuropsychological tests assessing psychomotor speed, attention, memory, language, visuoconstructional, and executive functions, as well as subjective mood ratings of depression and anxiety. RESULTS: Average age was 28.2 years (SD = 7.5) with 12-17 years of education. Participants were disabled by tics, with a tic frequency of 50-80 per minute before surgery. At baseline, subjects' cognitive function was generally average, although mild deficits in sequencing and verbal fluency were present, as were clinically mild obsessive-compulsive symptoms. At 3 months of continuous DBS (5 months after implantation), 3 of 5 participants had clinical reductions in motor and sonic tics. Cognitive scores generally remained stable, but declines of moderate to large effect size (Cohen's d > 0.6) in verbal fluency, visual immediate memory, and reaction time were observed. Fewer symptoms of depression and anxiety, as well as fewer obsessions and compulsions, were reported after 3 months of continuous high-frequency DBS. CONCLUSIONS: Bilateral centromedian-parafascicular thalamic DBS for medically refractory TS shows promise for treatment of medically refractory TS without marked neuropsychological morbidity. Symptoms of depression and anxiety improved.

Requirement of longitudinal synchrony of epileptiform discharges in the hippocampus for seizure generation: a pilot study.

OBJECT: The goal in this study was to assess the role of longitudinal hippocampal circuits in the generation of interictal and ictal activity in temporal lobe epilepsy (TLE) and to evaluate the effects of multiple hippocampal transections (MHT). METHODS: In 6 patients with TLE, the authors evaluated the synchrony of hippocampal interictal and ictal epileptiform discharges by using a cross-correlation analysis, and the effect of MHT on hippocampal interictal spikes was studied. Five of the 6 patients were studied with depth electrodes, and epilepsy surgery was performed in 4 patients (anterior temporal lobectomy in 1 and MHT in 3). RESULTS: Four hundred eighty-two (95.1%) of 507 hippocampal spikes showed an anterior-to-posterior propagation within the hippocampus, with a fixed peak-to-peak interval. During seizures, a significant increase of synchronization between different hippocampal regions and between the hippocampus and the ipsilateral anterior parahippocampal gyrus was observed in all seizures. An ictal increase in synchronization between the hippocampus and ipsilateral amygdala was seen in only 24.1% of the seizures. No changes in synchronization were noticed during seizures between the hippocampi and the amygdala on either side. The structure leading the epileptic seizures varied over time during a given seizure and also from one seizure to another. Spike analysis during MHT demonstrated that there were two spike populations that reacted differently to this procedure--namely, 1) spikes that showed maximum amplitude at the head of the hippocampus (type H); and 2) spikes that showed the highest amplitude at the hippocampal body (type B). A striking decrease in amplitude and frequency of type B spikes was noticed in all 3 patients after transections at the head or anterior portion of the hippocampal body. Type H spikes were seen in 2 cases and did not change in amplitude and frequency throughout MHT. Type B spikes showed constantly high cross-correlation values in different derivations and a relatively fixed peak-to-peak interval before MHT. This fixed interpeak delay disappeared after the first transection, although high cross-correlation values persisted unchanged. All patients who underwent MHT remained seizure free for more than 2 years. CONCLUSIONS: These data suggest that synchronized discharges involving the complete anterior-posterior axis of the hippocampal/parahippocampal (H/P) formation underlie the spread of epileptiform discharges outside the H/P structures and, therefore, for the generation of epileptic seizures originating in the H/P structures. This conclusion is supported by the following observations. 1) Hippocampal spikes are consistently synchronized in the whole hippocampal structures, with a fixed delay between the different hippocampal areas. 2) One or two transections between the head and body of the hippocampal formation are sufficient to abolish hippocampal spikes that are synchronized along the anterior-posterior axis of the hippocampus. 3) Treatment with MHT leads to seizure freedom in patients with H/P epilepsy.

Triple pathology in epilepsy: coexistence of cavernous angiomas and cortical dysplasias with other lesions.

Coexistence of cortical dysplasias (CD) with cavernomas has rarely been reported. We reviewed our surgical specimens from patients who underwent surgery for pharmacoresistant epilepsy between 2003 and 2008, and identified seven cases with cavernoma, of whom two had overlying CD. In addition, each of these patients had a third form of a potentially epileptogenic lesion: hippocampal sclerosis in one, and venous angioma in the other. We conclude that CD is heterogeneous, with milder forms appearing to co-exist with other pathologies, including vascular abnormalities and hippocampal sclerosis.

Radiosurgery for glomus jugulare tumors.

Glomus jugulare tumors arise from adventitial chemoreceptor tissue in the jugular bulb. Although histologically benign, these tumors can be locally aggressive because of their proximity to the lower cranial nerves and major vascular structures. Traditional treatment involves microsurgical removal with or without endovascular embolization, but morbidity following total resection can result in injury to the facial and lower cranial nerves. Radiosurgery has recently emerged as a promising alternative to older therapeutic strategies for treatment of glomus jugulare tumors. This article reviews the latest benefits of radiosurgery and demonstrates how this modality represents an effective treatment option for glomus jugulare tumors with excellent tumor control and low risk for morbidity. In addition, this article will detail the role of minimally invasive sub-total resection of glomus jugulare tumors as a surgical complement to gamma knife therapy.

Staged Gamma Knife radiosurgery after tailored surgical resection: a novel treatment paradigm for glomus jugulare tumors.

OBJECT: Although benign and slow growing, glomus jugulare tumors can be locally aggressive because of their proximity to lower cranial nerves and major vascular structures. Surgical resection frequently leads to complications, and radiosurgery alone often does not relieve symptoms. We report a novel treatment paradigm of tailored surgical resection followed by staged radiosurgery that allows for tissue diagnosis and immediate improvement of symptoms and tumor control without the morbidity of radical surgical resection. METHODS: Five patients with glomus jugulare tumors and contraindications to extensive surgery each underwent an outpatient otologic procedure to resect the portion of the tumor in the middle ear and mastoid with no attempt to remove tumor in the jugular bulb. Each patient returned 2-5 months later for Gamma Knife radiosurgery to the remainder of the tumor, which consisted of one 15-Gy dose prescribed to the 50% isodose curve. Patients were followed through outpatient visits and surveillance MR imaging for up to 3 years. RESULTS: All patients were successfully treated as outpatients. Each had improvement or resolution of pulsatile tinnitus and otalgia and preserved or improved hearing. One patient developed a delayed facial palsy prior to radiosurgery that resolved completely; there were no other changes in cranial nerve function after either procedure. Tumor volume was stable or reduced in all patients at most recent follow-up, and there were no immediate or delayed complications. CONCLUSIONS: Staged outpatient microsurgical and radiosurgical therapy for glomus jugulare tumors in the symptomatic patient is safe and yields favorable results regarding tumor size, tinnitus, hearing and cranial nerve status.

Modeling video tic counts in a crossover trial of deep brain stimulation for Tourette syndrome.

A recent pilot crossover study of deep brain stimulation for Tourette syndrome involved the counting of motor and sonic tics from video recordings of patients. The evaluation of a five-minute video (divided into ten 30-second segments) in each of eight intervention states per patient was found to be very tedious and time-consuming. The present study sought to determine the statistical implications of reducing this data collection burden. To make maximal use of data from the small sample (n=5) pilot study, we fit linear mixed effects models to the tic count data. As suggested by an empirical examination of within-person correlations, a novel random effects covariance structure, which we refer to as a 'partitioned random effects model' was found to provide the best fit to the data. The best model for each tic type was then used to estimate relative efficiencies for specified data reductions. This analysis indicated that using a subset of five out of 10 segments would require only a 10% increase in sample size to maintain a specified power. Lastly, the bias of estimated treatment effects based on the reduced data collection was evaluated, and the particular five-segment subsets with the smallest estimated bias were determined.

Medically intractable seizures originating from the primary somatosensory hand area.

A 33-year-old woman had begun having intractable somatosensory seizures affecting the left hand since the age of 13 years. Occasionally, her seizures progressed to left arm posturing followed by secondary generalization. Scalp EEG revealed interictal epileptiform discharges in the right posterior quadrant, but with no ictal EEG correlates. Brain MRI showed a right temporal encephalomalacia, sparing mesial temporal structures, suggestive of a perinatal vascular insult. Ictal electrocorticogram, electrical stimulation mapping, and somatosensory evoked potentials localized the ictal onset to the hand area of the postcentral gyrus. Resection of that area resulted in total resolution of seizures with no significant lasting deficits. Potential complications of resecting the primary somatosensory hand area can be severe, as proprioceptive sensory loss may be permanent, resulting in significant disability. Such deficits may be temporary however, and the literature continues to report conflicting results regarding postsurgical outcome. Cortical plasticity may explain recovery of sensory deficits after partial resection of the primary somatosensory hand area. Multiple subpial transections of that area are sometimes performed to minimize functional deficits, but seizure control may be less optimal than with cortical resection.

Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome.

OBJECT: The severity of Tourette syndrome (TS) typically peaks just before adolescence and diminishes afterward. In some patients, however, TS progresses into adulthood, and proves to be medically refractory. The authors conducted a prospective double-blind crossover trial of bilateral thalamic deep brain stimulation (DBS) in five adults with TS. METHODS: Bilateral thalamic electrodes were implanted. An independent programmer established optimal stimulator settings in a single session. Subjective and objective results were assessed in a double-blind randomized manner for 4 weeks, with each week spent in one of four states of unilateral or bilateral stimulation. Results were similarly assessed 3 months after unblinded bilateral stimulator activation while repeated open programming sessions were permitted. RESULTS: In the randomized phase of the trial, a statistically significant (p < 0.03, Friedman exact test) reduction in the modified Rush Video-Based Rating Scale score (primary outcome measure) was identified in the bilateral on state. Improvement was noted in motor and sonic tic counts as well as on the Yale Global Tic Severity Scale and TS Symptom List scores (secondary outcome measures). Benefit was persistent after 3 months of open stimulator programming. Quality of life indices were also improved. Three of five patients had marked improvement according to all primary and secondary outcome measures. CONCLUSIONS: Bilateral thalamic DBS appears to reduce tic frequency and severity in some patients with TS who have exhausted other available means of treatment.

Intraoperative MRI with a rotating, tiltable surgical table: a time use study and clinical results in 122 patients.

OBJECTIVE: The objective of our study was to evaluate intraoperative low-field MRI for the frequency and duration of imaging sessions needed during surgery, the direct additional procedure time attributable to imaging, and the proportion of cases in which information provided by intraoperative MRI led to a change in the procedure or otherwise was deemed valuable by operating surgeons. MATERIALS AND METHODS: One hundred twenty-two patients (65 males, 57 females; age range, 6-77 years; mean age, 43.8 years) underwent 130 neurosurgical and ENT procedures (106 craniotomies, 17 transsphenoidal pituitary resections, three biopsies, three intracranial cyst aspirations or injections, and one skull base resection) in a specially designed surgical MRI suite equipped with a 0.2-T imager and a prototype rotating, tiltable surgical table. The intraoperative MR sequences included free induction with steady-state precession (fast imaging with steady-state precession [FISP]), steady-state free precession T2-weighted, reverse fast imaging with steady-state free precession (PSIF), FLASH, spin-echo T1-weighted, turbo spin-echo (TSE) T2-weighted, and TSE FLAIR. Each case was analyzed for the number of imaging sessions, duration of each session, total imaging time during surgery, and impact of imaging information on procedure. RESULTS: Each patient underwent between one and five intraor postoperative imaging sessions. Imaging times were 1.7 seconds-8 minutes 31 seconds per sequence. The mean total imaging time was 35 minutes 17 seconds per surgical procedure. Imaging was continuous during biopsy and cyst aspiration procedures and averaged 200.67 and 54.66 minutes, respectively. Additional surgical resection based on intraoperative imaging findings was performed in 72.8% of the cases. CONCLUSION: Intraoperative low-field MRI provides valuable information for surgical decision making that is predominantly related to detection of residual tumor and the exclusion of complications. The benefits of this technology surpass the time cost associated with its implementation when using proper imaging strategies.

12 Gy gamma knife radiosurgical volume is a predictor for radiation necrosis in non-AVM intracranial tumors.

PURPOSE: To determine whether the 12-Gy radiosurgical volume (12-GyV) correlates with the development of postradiosurgical imaging changes suggestive of radiation necrosis in patients treated for non-arteriovenous malformation (non-AVM) intracranial tumors with gamma knife stereotactic radiosurgery (GKSRS). METHODS AND MATERIALS: A retrospective single-institution review of 129 patients with 198 separate non-AVM tumors was performed. Patients were followed with magnetic resonance imaging (MRI) and physical examinations at 3- to 6-month intervals. Patients who developed postradiosurgical MRI changes suggestive of radiation necrosis were labeled as having either symptomatic radiation necrosis (S-NEC) if they experienced any decline in neurologic examination associated with the imaging changes, or asymptomatic radiation necrosis (A-NEC) if they had a stable or improving neurologic examination. RESULTS: 12-GyV correlated with risk of S-NEC, which was 23% (for 12-GyV of 0-5 cc), 20% (5-10 cc), 54% (10-15 cc), and 57% (>15 cc). The risk of A-NEC did not significantly change with 12-GyV. Logistic regression analyses showed that the following factors were associated with the development of S-NEC: 12-GyV (p<0.01), occipital and temporal lesions (p<0.01), previous whole-brain radiotherapy (p=0.03), and male sex (p=0.03). Radiosurgical plan conformality did not correlate with the development of S-NEC. CONCLUSION: The risk of S-NEC, but not A-NEC after GKSRS for non-AVM tumors correlates with 12-GyV, and increases significantly for 12-GyV>0 cc.

Computer-assisted neurosurgery.

Computer-assisted neurosurgery has become so successful that it is rapidly becoming indistinguishable from, quite simply, neurosurgery. This trend promises to accelerate over the next several decades, bringing considerable benefit to the patients we care for. From a pragmatic point of view, can we identify specific instances in which clinical practice has been altered by computer assistance? During craniotomies for the resection of brain tumors, this technology has led to a greater standardization within and among practitioners for the expected degree of resection and the risk of morbidity and mortality. Minimally invasive approaches are transforming the practice of cranial base surgery. This technological trend has made craniotomy for biopsy virtually obsolete in the face of frameless stereotactic techniques. Functional neurosurgery has benefited from these technologies, as deep brain stimulation surgery has become the standard of care for most cases of movement disorder surgery. Extratemporal epilepsy due to cortical dysplasia has proven especially amenable to image-guided surgical techniques that integrate electrophysiological monitoring to refine the target of resection. New surgical procedures made possible by computer assistance include minimally invasive spine surgery, endovascular procedures, resections of low-grade nonenhancing gliomas, and stereotactic radiosurgery. A program for future research and development in this field would include: Electronic patient medical records. Automatic dynamic and elastic registration Novel surgical instrumentation guided by augmented reality Real-time feedback using anatomic and functional information Active robotic servo control systems to amplify neurosurgical capabilities Outcomes analysis-driven refinement of neurosurgical interventions. It is apparent that using computer assistance in neurosurgery has begun a process that will irrevocably transform all of neurosurgical practice itself. It must be neurosurgeons themselves who provide the leadership to transcend the potentially distracting aspects of this technological revolution. What shall not change is the commitment that we, as neurosurgeons, have to the welfare of our patients.

Treatment of glomus jugulare tumors in patients with advanced age: planned limited surgical resection followed by staged gamma knife radiosurgery: a preliminary report.

OBJECTIVE: To minimize treatment comorbidities in glomus jugulare tumor patients with advanced age while reducing pulsatile tinnitus and preserving or improving residual hearing using a limited middle ear/mastoid tumor resection and postoperative gamma knife radiosurgery to tumor remnants in the jugular foramen region. STUDY DESIGN: Retrospective consecutive case review of five patients. SETTING: Tertiary referral, academic medical center. PATIENTS: Patients with advanced age (mean, 69.6 yr; range, 61-78 yr) harboring symptomatic glomus jugulare tumors. INTERVENTION: All patients were treated with resection of middle ear and mastoid portions of tumor and subsequent gamma knife radiosurgery to jugular foramen portion of tumor. MAIN OUTCOME MEASURES: Length of hospitalization; hearing, pulsatile tinnitus, cranial nerve, and tumor control status. RESULTS: All patients were treated on an outpatient surgical basis without the need for blood transfusion. There were no incidents of a change in cranial nerve status (Cranial Nerves VII, IX, X, XI, and XII) in the immediate postoperative period. All patients had improvement or resolution of pulsatile tinnitus with preservation or improvement of preoperative hearing levels. Tumor volume was stable or reduced in all patients at mean follow-up of 19 months (range, 11-24 mo). Gamma knife radiosurgery (mean peripheral dose of 15 Gy) was not associated with any significant immediate or delayed complications. CONCLUSION: Short-term data reveals that staged microsurgical and radiosurgical therapy for glomus jugulare tumors in the symptomatic patient with advanced age is safe and yields favorable results regarding tinnitus, hearing, and cranial nerve status. Long-term data are needed to further evaluate the effectiveness of this treatment algorithm before extrapolating this treatment option to younger patients.

Low-dose radiosurgery for benign intracranial lesions.

This study assesses the efficacy and neurotoxicity of radiosurgical treatment of benign intracranial tumors using a linear accelerator, with relatively low dose and homogeneous dosimetry. Between June 1998 and July 2000, 27 patients were treated for benign lesions with radiosurgery using a 6-MV linear accelerator-based X-knife system and circular collimators. The lesions included schwannoma, meningioma, papillary cyst adenoma, and hemangioblastoma. Five patients had tissue diagnosis. The mean peripheral dose to the tumor margin was 12.8 Gy. The mean dose to the isocenter was 16.3 Gy. One to five isocenters were used to treat these lesions, with a mean of 10 arcs per isocenter and mean collimator size of 1.25 cm. Follow-up information was available on all patients, with a mean follow-up duration of 33 months. Six patients (22%) had improved symptoms and 21 (78%) had stable symptoms. Eight patients (30%) had regression of tumor and 19 had stable disease (70%). No patient had tumor progression, and Radiation Therapy Oncology Group (RTOG) grade III or IV toxicity did not occur in any patients. In 3 patients (11%), RTOG grade I or grade II neurotoxicity developed. Of these, one patient had worsening of a preexisting VIIth nerve deficit that required temporary oral methylprednisolone, and in two patients a mild trigeminal deficit developed that did not require any medical intervention. Low-dose homogeneous radiosurgery using a linear accelerator is an effective treatment for benign intracranial tumors. If lower, more homogeneous radiation doses produce responses as durable as higher doses, then toxicity might be further reduced.

Effect of changing patient position from supine to prone on the accuracy of a Brown-Roberts-Wells stereotactic head frame system.

OBJECTIVE: Despite the growing popularity of frameless image-guided surgery systems, stereotactic frame systems are widely accepted by neurosurgeons and are commonly used to perform biopsies, functional procedures, and stereotactic radiosurgery. We investigated the accuracy of the Brown-Roberts-Wells stereotactic frame system when the mechanical load on the frame changes between preoperative imaging and the intervention because of different patient position: supine during imaging, prone during intervention. METHODS: We analyzed computed tomographic images acquired from 14 patients who underwent stereotactic biopsy, deep brain stimulator implantation, or radiosurgery. Two images were acquired for each patient, one with the patient in the supine position and one in the prone position. The prone images were registered to the respective supine images by use of an intensity-based registration algorithm, once using only the frame and once using only the head. The difference between the transformations produced by these two registrations describes the movement of the patient's head with respect to the frame. RESULTS: The maximum frame-based registration error between the supine and prone positions was 2.8 mm; it was more than 2 mm in two patients and more than 1.5 mm in six patients. Anteroposterior translation is the dominant component of the difference transformation for most patients. In general, the magnitude of the movement increased with brain volume, which is an index of head weight. CONCLUSION: To minimize frame-based registration error caused by a change in the mechanical load on the frame, stereotactic procedures should be performed with the patient in the identical position during imaging and intervention.

Integration of neurosurgical image guidance and an intraoperative magnetic resonance scanner. The University Hospitals of Cleveland experience.

BACKGROUND: Intraoperative magnetic resonance (MR) imaging has been employed as an alternative to image guidance using preoperative images. We integrated both systems to evaluate their clinical use. METHODS: The BrainLAB VectorVision system was integrated in an intraoperative Siemens Open Viva 0.2-tesla MR system. Clinical experience was assessed. RESULTS: Patterns of intraoperative imaging emerged, and benefit was seen in registering preoperative and intraoperative images. CONCLUSIONS: This integrated system has clinically observed effects on imaging, navigation, and surgery.