Ethan Taub

Directional deep brain stimulation: an intraoperative double-blind pilot study

Deep brain stimulation of different targets has been shown to drastically improve symptoms of a variety of neurological conditions. However, the occurrence of disabling side effects may limit the ability to deliver adequate amounts of current necessary to reach the maximal benefit. Computed models have suggested that reduction in electrode size and the ability to provide directional stimulation could increase the efficacy of such therapies. This has never been demonstrated in humans. In the present study, we assess the effect of directional stimulation compared to omnidirectional stimulation. Three different directions of stimulation as well as omnidirectional stimulation were tested intraoperatively in the subthalamic nucleus of 11 patients with Parkinsons disease and in the nucleus ventralis intermedius of two other subjects with essential tremor. At the trajectory chosen for implantation of the definitive electrode, we assessed the current threshold window between positive and side effects, defined as the therapeutic window. A computed finite element model was used to compare the volume of tissue activated when one directional electrode was stimulated, or in case of omnidirectional stimulation. All but one patient showed a benefit of directional stimulation compared to omnidirectional. A best direction of stimulation was observed in all the patients. The therapeutic window in the best direction was wider than the second best direction (P = 0.003) and wider than the third best direction (P = 0.002). Compared to omnidirectional direction, the therapeutic window in the best direction was 41.3% wider (P = 0.037). The current threshold producing meaningful therapeutic effect in the best direction was 0.67 mA (0.3-1.0 mA) and was 43% lower than in omnidirectional stimulation (P = 0.002). No complication as a result of insertion of the directional electrode or during testing was encountered. The computed model revealed a volume of tissue activated of 10.5 mm(3) in omnidirectional mode, compared with 4.2 mm(3) when only one electrode was used. Directional deep brain stimulation with a reduced electrode size applied intraoperatively in the subthalamic nucleus as well as in the nucleus ventralis intermedius of the thalamus significantly widened the therapeutic window and lowered the current needed for beneficial effects, compared to omnidirectional stimulation. The observed side effects related to direction of stimulation were consistent with the anatomical location of surrounding structures. This new approach opens the door to an improved deep brain stimulation therapy. Chronic implantation is further needed to confirm these findings.

Cognitive training in Parkinson disease Cognition-specific vs nonspecific computer training

Objective: In this study, we compared a cognition-specific computer-based cognitive training program with a motion-controlled computer sports game that is not cognition-specific for their ability to enhance cognitive performance in various cognitive domains in patients with Parkinson disease (PD). Methods: Patients with PD were trained with either a computer program designed to enhance cognition (CogniPlus, 19 patients) or a computer sports game with motion-capturing controllers (Nintendo Wii, 20 patients). The effect of training in 5 cognitive domains was measured by neuropsychological testing at baseline and after training. Group differences over all variables were assessed with multivariate analysis of variance, and group differences in single variables were assessed with 95% confidence intervals of mean difference. The groups were similar regarding age, sex, and educational level. Results: Patients with PD who were trained with Wii for 4 weeks performed better in attention (95% confidence interval: −1.49 to −0.11) than patients trained with CogniPlus. Conclusions: In our study, patients with PD derived at least the same degree of cognitive benefit from non–cognition-specific training involving movement as from cognition-specific computerized training. For patients with PD, game consoles may be a less expensive and more entertaining alternative to computer programs specifically designed for cognitive training. Classification of evidence: This study provides Class III evidence that, in patients with PD, cognition-specific computer-based training is not superior to a motion-controlled computer game in improving cognitive performance.

Sonication of catheter tips for improved detection of microorganisms on external ventricular drains and ventriculo-peritoneal shunts

The diagnosis of infections involving internal or external neurosurgical drainage devices is challenging, and to our knowledge no single reliable microbiological test exists. We used sonication to study bacterial colonization in 14 explanted external ventricular drains (EVD) and 13 ventriculo-peritoneal shunt (VPS) devices. This technique dislodges biofilm bacteria from the surface of implanted materials before culture. Removed devices were sonicated in saline (40 kHz, 1 minute, 0.25 W/cm(2)), the resulting fluid was cultured aerobically and anaerobically at 37°C, and bacterial growth was counted. Ventricular cerebrospinal fluid (CSF) was cultured separately. In the EVD group, sonication cultures grew significantly more bacteria (64%, 9/14) than cultures of aspirated ventricular CSF (14%, 2/14). In the VPS group the difference was not significant. Positive sonication cultures of EVD catheters yielded a median of >100 colony forming units (CFU) (range, 60-800). For positive sonication cultures of VPS, the median was 1000 CFU (range, 20-100,000). All patients with bacteria in their CSF also had positive sonication cultures from the removed device. Of the five patients with sterile or presumably contaminated CSF cultures but positive sonication cultures of removed shunts, one became afebrile after removal of the EVD, two developed meningitis and two remained asymptomatic. Sonication culture of EVD appears to improve the microbiological assessment of device-related infection and it corroborates with CSF cultures of revision surgery for VPS. Sonication of the removed EVD tip may raise awareness for the onset of meningitis.

Growth retardation and bilateral cataracts followed by anaplastic meningioma 23 years after high-dose cranial and whole-body irradiation for acute lymphoblastic leukemia : case report and review of the literature

SummaryWe report a case of meningioma diagnozed 23 years after high-dose cranial and whole-body irradiation for the treatment of acute lymphocytic leukemia (ALL). Radiotherapy in this case also caused early radiation injury to the lenses and the pituitary gland, with growth retardation and mineralizing angiopathy. Radiation-induced meningiomas are more commonly malignant, more commonly multiple, and more likely to recur after resection than non-radiation-induced meningiomas. Survivors of childhood ALL treated with high-dose cranial irradiation are at risk both for early radiation injury in radiosensitive organs, such as the lens and pituitary gland, and for the later development of a radiation-induced meningioma.

Older Candidates for Subthalamic Deep Brain Stimulation in Parkinson's Disease Have a Higher Incidence of Psychiatric Serious Adverse Events.

Objective: To investigate the incidence of serious adverse events (SAE) of subthalamic deep brain stimulation (STN-DBS) in elderly patients with Parkinsons disease (PD). Methods: We investigated a group of 26 patients with PD who underwent STN-DBS at mean age 63.2 ± 3.3 years. The operated patients from the EARLYSTIM study (mean age 52.9 ± 6.6) were used as a comparison group. Incidences of SAE were compared between these groups. Results: A higher incidence of psychosis and hallucinations was found in these elderly patients compared to the younger patients in the EARLYSTIM study (p < 0.01). Conclusions: The higher incidence of STN-DBS-related psychiatric complications underscores the need for comprehensive psychiatric pre- and postoperative assessment in older DBS candidates. However, these psychiatric SAE were transient, and the benefits of DBS clearly outweighed its adverse effects.

A Review of the Literature on the Transciliary Supraorbital Keyhole Approach

BACKGROUND Conventional craniotomy approaches involve substantial soft tissue manipulation that can cause complications. The transciliary supraorbital keyhole approach was developed to avoid these complications. The aim of this review is to evaluate the safety and the effectiveness of the transciliary supraorbital keyhole approach. METHODS We searched the PubMed/Medline database for full-text publications from 1996 onward containing data on 100 or more cases of aneurysm clipping or tumor resection by the transciliary supraorbital keyhole approach. The primary outcome was the incidence of approach-related complications. The secondary outcomes were the aneurysm occlusion rate and the extent of tumor resection. RESULTS Eight publications met the eligibility criteria. All publications were of the retrospective case-series or case-cohort type without any independent assessment of outcomes. The risk of bias at the individual study level may thus have influenced any conclusions drawn from the overall study population, which included 2783 patients with 3085 lesions (2508 aneurysms and 577 tumors). Approach-related complications included 3.3% cerebrospinal fluid collection or leak, 4.3% permanent and 1.6% temporary supraorbital hypesthesia, 2.9% permanent and 1% temporary facial nerve palsy, and 1% wound healing disturbance or wound infection. Complete aneurysm clipping was achieved in 97% of cases. Complete tumor resection in 90% of cases. The overall surgical revision rate was 2.5%. The esthetic outcome was typically reported as highly acceptable. CONCLUSIONS This approach may represent a safe, effective, and less invasive alternative to conventional craniotomies in experienced hands and for a well-selected subset of patients. However, higher-level evidence is needed to confirm this hypothesis.

An epidural neuroblastoma causing spinal cord compression in a 67-year-old woman

We report a case of disseminated neuroblastoma (NB) causing epidural spinal cord compression in a 67-year-old woman. Because NB is primarily a tumor of infancy and childhood, less is known about its clinical course and optimal treatment in adults. This patient was treated with a thoracic laminectomy and tumor resection; polychemotherapy with one cycle of vindesine, cisplatin, and etoposide; one cycle of vincristine, dacarbazine, ifosfamide, and doxorubicin; and radiotherapy to the spine. She remained able to walk but died 8.5 months later of diffuse systemic tumor progression.

Intended Near-Total Removal of Koos Grade IV Vestibular Schwannomas: Reconsidering the Treatment Paradigm.

BACKGROUND The goals of treating Koos grade IV vestibular schwannomas are to relieve brainstem compression, preserve or restore neurological function, and achieve long‐term tumor control while minimizing tumor‐ and treatment‐related morbidity. OBJECTIVE To propose a treatment paradigm involving the intentional near‐total removal of Koos grade IV vestibular schwannomas, in which a small amount of residual tumor is not dissected off the cisternal portion of the facial nerve. Patients are then followed by a wait‐and‐scan approach. Any subsequent volumetric progression of the residual tumor is treated with radiosurgery. METHODS This is a case series of 44 consecutive unselected patients who underwent intended near‐total resection of a Koos grade IV vestibular schwannoma through a retrosigmoid approach from January 2009 to December 2015. Pre‐ and postoperative volumetric analyses were performed on routine magnetic resonance imaging sequences (constructive interference in steady state and gadolinium‐enhanced T1‐weighted sequence). RESULTS The mean preoperative tumor volume was 10.9 cm3. The mean extent of resection was 89%. At the last clinical follow‐up, facial nerve function was good [House and Brackmann (HB) I‐II] in 89%, fair (HB III) in 9%, and poor (HB IV‐VI) in 2% of the patients. At the last radiological follow‐up, the residual tumor had become smaller or remained the same size in 84% of patients. Volumetric progression was negatively correlated with the original extent of resection and positively correlated with postoperative residual tumor volume (P = .01, P < .001, respectively). CONCLUSION Intended near‐total removal results in excellent preservation of facial nerve function and has a low recurrence rate. Any progressive residual tumor may be treated by radiosurgery.

A novel assistive method for rigidity evaluation during deep brain stimulation surgery using acceleration sensors

OBJECTIVE Despite the widespread use of deep brain stimulation (DBS) for movement disorders such as Parkinsons disease (PD), the exact anatomical target responsible for the therapeutic effect is still a subject of research. Intraoperative stimulation tests by experts consist of performing passive movements of the patients arm or wrist while the amplitude of the stimulation current is increased. At each position, the amplitude that best alleviates rigidity is identified. Intrarater and interrater variations due to the subjective and semiquantitative nature of such evaluations have been reported. The aim of the present study was to evaluate the use of an acceleration sensor attached to the evaluators wrist to assess the change in rigidity, hypothesizing that such a change will alter the speed of the passive movements. Furthermore, the combined analysis of such quantitative results with anatomy would generate a more reproducible description of the most effective stimulation sites. METHODS To test the reliability of the method, it was applied during postoperative follow-up examinations of 3 patients. To study the feasibility of intraoperative use, it was used during 9 bilateral DBS operations in patients suffering from PD. Changes in rigidity were calculated by extracting relevant outcome measures from the accelerometer data. These values were used to identify rigidity-suppressing stimulation current amplitudes, which were statistically compared with the amplitudes identified by the neurologist. Positions for the chronic DBS lead implantation that would have been chosen based on the acceleration data were compared with clinical choices. The data were also analyzed with respect to the anatomical location of the stimulating electrode. RESULTS Outcome measures extracted from the accelerometer data were reproducible for the same evaluator, thus providing a reliable assessment of rigidity changes during intraoperative stimulation tests. Of the 188 stimulation sites analyzed, the number of sites where rigidity-suppressing amplitudes were found increased from 144 to 170 when the accelerometer evaluations were considered. In general, rigidity release could be observed at significantly lower amplitudes with accelerometer evaluation (mean 0.9 ± 0.6 mA) than with subjective evaluation (mean 1.4 ± 0.6 mA) (p < 0.001). Of 14 choices for the implant location of the DBS lead, only 2 were the same for acceleration-based and subjective evaluations. The comparison across anatomical locations showed that stimulation in the fields of Forel ameliorates rigidity at similar amplitudes as stimulation in the subthalamic nucleus, but with fewer side effects. CONCLUSIONS This article describes and validates a new assistive method for assessing rigidity with acceleration sensors during intraoperative stimulation tests in DBS procedures. The initial results indicate that the proposed method may be a clinically useful aid for optimal DBS lead placement as well as a new tool in the ongoing scientific search for the optimal DBS target for PD.

Cerebral venous thrombosis requiring invasive treatment for elevated intracranial pressure in women with combined hormonal contraceptive intake: risk factors, anatomical distribution, and clinical presentation

OBJECTIVE Women taking combined hormonal contraceptives (CHCs) are generally considered to be at low risk for cerebral venous thrombosis (CVT). When it does occur, however, intensive care and neurosurgical management may, in rare cases, be needed for the control of elevated intracranial pressure (ICP). The use of nonsurgical strategies such as barbiturate coma and induced hypothermia has never been reported in this context. The objective of this study is to determine predictive factors for invasive or surgical ICP treatment and the potential complications of nonsurgical strategies in this population. METHODS The authors conducted a 2-center, retrospective chart review of 168 cases of CVT in women between 2000 and 2012. Eligible patients were classified as having had a mild or a severe clinical course, the latter category including all patients who underwent invasive or surgical ICP treatment and all who had an unfavorable outcome (modified Rankin Scale score ≥ 3 or Glasgow Outcome Scale score ≤ 3). The Mann-Whitney U-test was used for continuous parameters and Fishers exact test for categorical parameters, and odds ratios were calculated with statistical significance set at p ≤ 0.05. RESULTS Of the 168 patients, 57 (age range 16-49 years) were determined to be eligible for the study. Six patients (10.5%) required invasive or surgical ICP treatment. Three patients (5.3%) developed refractory ICP > 30 mm Hg despite early surgical decompression; 2 of them (3.5%) were treated with barbiturate coma and induced hypothermia, with documented infectious, thromboembolic, and hemorrhagic complications. Coma on admission, thrombosis of the deep venous system with consecutive hydrocephalus, intraventricular hemorrhage, and hemorrhagic venous infarction were associated with a higher frequency of surgical intervention. Coma, quadriparesis on admission, and hydrocephalus were more commonly seen among women with unfavorable outcomes. Thrombosis of the transverse sinus was less common in patients with an unfavorable outcome, with similar distribution in patients needing invasive or surgical ICP treatment. CONCLUSIONS The need for invasive or surgical ICP treatment in women taking CHCs who have CVT is partly predictable on the basis of the clinical and radiological findings on admission. The use of nonsurgical treatments for refractory ICP, such as barbiturate coma and induced hypothermia, is associated with systemic infectious and hematological complications and may worsen morbidity in this patient population. The significance of these factors should be studied in larger multicenter cohorts.