James McInerney

The role of intracranial electrode reevaluation in epilepsy patients after failed initial invasive monitoring.

Summary: Purpose: Intracranial electrode recording often provides localization of the site of seizure onset to allow epilepsy surgery. In patients whose invasive evaluation fails to localize seizure origin, the utility of further invasive monitoring is unknown. This study was undertaken to explore the hypothesis that a second intracranial investigation is selected patients warrants consideration and can lead to successful epilepsy surgery.

Long-Term Seizure Outcome following Corpus Callosotomy in Children

Introduction: The long-term outcome of pediatric patients undergoing corpus callosotomy (CC) for palliative control of medically intractable seizures is presented. Methods: During a 27-year period, 43 patients, 20 years of age or younger, underwent CC for seizure palliation and had a minimum of 1 year follow-up. Seizure reduction and stability of that outcome for individual seizure types and for most disabling seizure were reviewed. Results: Overall, 63% of the seizures documented showed a good response. For the most disabling seizure, 56% of the patients had good outcomes. Changes in outcome status occurred within the first 6 months, and outcome was largely maintained after that point. Conclusion: Callosotomy achieves the goal of seizure palliation in more than half of the patients, with stable, good outcomes being maintained in the majority of patients.

Perioperative exacerbation of valproic acid-associated hyperammonemia: a clinical and genetic analysis.

We present a case of significant deterioration of chronic hyperammonemia after general anesthesia for neurosurgery despite aggressive treatment. Preoperative evaluation demonstrated that hyperammonemia was most likely related to valproic acid treatment. Genomic analysis revealed that the patient was heterozygotic for a missense polymorphism in the carbamoyl phosphate synthase 1 gene (4217C>A, rs1047891). This mutation was previously suggested to be associated with chronic hyperammonemia. Replacement of threonine with asparagine decreases the activity of carbamoyl phosphate synthase in the urea cycle. Genetic screening can potentially identify a population at risk before initiation of antiepileptic therapy.

Coregistered Ultrasound as a Neurosurgical Guide

Introduction: The dynamic nature and three dimensionality of ultrasound data can be utilized to enhance the capabilities of image guidance systems. Methods: Coregistration of ultrasound data was done using an electromagnetic digitizer, and subsequent ultrasound images were correlated with preoperative MRI studies. Thirty-two patients undergoing craniotomy were investigated in this manner. Results: Phantom testing done with a rigid stylus and 3D ultrasound tracker demonstrated an accuracy of 1.36 ± 1.67 mm in determining the location of a point. Thirty-two clinical cases were coregistered without difficulty. Conclusion: Coregistered ultrasound is a useful methodology that can aid in neuronavigation.

A Prospective Evaluation of an Outpatient Assessment of Postural Instability to Predict Risk of Falls in Patients with Parkinson's Disease Presenting for Deep Brain Stimulation

Postural instability (PI) and falls, major causes of morbidity in patients with PD, are often overlooked. DBS is a mainstay therapy for Parkinsons disease (PD) and has been purported to both worsen and improve PI. An effective PI evaluation that can predict fall risk in patients with PD presenting for DBS is needed.

An Analysis of Scalp Thickness and Other Novel Risk Factors for Deep Brain Stimulator Infections.

Introduction: Deep brain stimulator (DBS) infections are a persistent problem for patients undergoing this procedure. They may require further surgery, treatment with antibiotics, or even removal of the device. To date, no consensus exists on the best practices to avoid DBS infections or what factors predispose patients to an eventual infection. The goal of this study was to examine several patient factors for association with DBS infection. Methods: A single-center, single-surgeon quality improvement database was queried. All patients who experienced an infection were identified. The primary variable analyzed was scalp thickness. Other pre-specified, secondary variables included routine intraoperative cultures, operative time, diagnosis, and age. Results: None of the independent variables examined were significantly associated with DBS infections. Only two of the 46 infections qualified as surgical site infections as defined by the Centers for Disease Control. Conclusion: DBS infections are independent of all of the predictor variables analyzed. Surgical site infections, according to traditional definitions, are not the optimal definition for evaluating DBS infections/erosions. New studies must examine new variables that are not routinely gathered in this population. Also, because of the rare event rates and difficulty in randomizing patients to exposures, a large, multicenter registry may be the optimal study design to solve this clinical problem.

Deep Brain Stimulation for Parkinson Disease Does not Worsen or Improve Postural Instability: A Prospective Cohort Trial

BACKGROUND Falls and postural instability (PI) are major sources of morbidity in Parkinson disease (PD). Deep brain stimulation (DBS) is a major therapy for PD. The effects of DBS on PI and falls remain controversial. OBJECTIVE To study if DBS worsens PI, validated measures of PI (Timed Up and Go, Berg Balance Scale, Unified Parkinsons Disease Rating Scale 3.12 [Pull Test], and the Biodex Sway Index with eyes closed on a firm and soft surface) and reported falls were used to prospectively evaluate the effect of DBS on PI at 3 and 12 mo postoperatively compared to baseline measurements. The primary outcomes were a positive result on 4 out of the 5 PI tests and falls. METHODS Patients presenting for DBS were prospectively enrolled and evaluated at presentation and, 3 and 12 mo postoperatively. All tests were performed at each visit. RESULTS At 3 mo 4 of 5 positive showed noninferiority to baseline, with a rate of 28% vs 41% (relative risk [RR] 0.8 [0.5-1.3]). At 12 mo, 4 of 5 positive had a rate of 35% vs 30% (RR 1.2 [0.8-1.8]) and falls had a rate of 54% vs 46% (RR 1.2 [0.6-2.3]). These did not meet criteria to prove noninferiority. Sensitivity analysis at 12 mo showed noninferiority for 4 of 5 (RR 0.9 [0.6-1.5]) but not falls (RR 1.1 [0.5-2.3]). CONCLUSION This evidence is consistent with the hypothesis that DBS does not worsen PI when measured at 3 and 12 mo postoperatively.

Gamma Knife radiosurgery of saccular aneurysms in a rabbit model

OBJECTIVEIntracranial aneurysms are vascular abnormalities associated with neurological morbidity and mortality due to risk of rupture. In addition, many aneurysm treatments have associated risk profiles that can preclude the prophylactic treatment of asymptomatic lesions. Gamma Knife radiosurgery (GKRS) is a standard treatment for trigeminal neuralgia, tumors, and arteriovenous malformations. Aneurysms associated with arteriovenous malformations have been noted to resolve after treatment of the malformation. The aim of this study was to determine the efficacy of GKRS treatment in a saccular aneurysm animal model.METHODSAneurysms were surgically produced using an elastase-induced aneurysm model in the right common carotid artery of 10 New Zealand white rabbits. Following initial observation for 4 years, each rabbit aneurysm was treated with a conformal GKRS isodose of 25 Gy to the 50% margin. Longitudinal MRI studies obtained over 2 years and terminal measures obtained at multiple time points were used to track aneurysm size and shape index modifications.RESULTSAneurysms did not rupture or involute during the observation period. Whole aneurysm and blood volume averages decreased with a linear trend, at rates of 1.7% and 1.6% per month, respectively, over 24 months. Aneurysm wall percent volume increased linearly at a rate of 0.3% per month, indicating a relative thickening of the aneurysm wall during occlusion. Nonsphericity of the average volume, aspect ratio, and isoperimetric ratio of whole aneurysm volume all remained constant. Histopathological samples demonstrated progressive reduction in aneurysm size and wall thickening, with subintimal fibrosis. Consistent shape indices demonstrate stable aneurysm patency and maintenance of minimal rupture risk following treatment.CONCLUSIONSThe data indicate that GKRS targeted to saccular aneurysms is associated with histopathological changes and linear reduction of aneurysm size over time. The results suggest that GKRS may be a viable, minimally invasive treatment option for intracranial aneurysm obliteration.

Response to Comment on: A Prospective Evaluation of an Outpatient Assessment of Postural Instability to Predict Risk of Falls in Patients with Parkinson's Disease Presenting for Deep Brain Stimulation

We thank the authors for their questions and thoughts on the problem of postural instability and the risk of falling in patients with Parkinson’s disease. To answer their questions, the majority of our patients’ elevated scores on part IV (complications of therapy) of the Unified Parkinson’s Disease Rating Scale were from subsections 4.5 and 4.6, which ask about the unpredictability of off times and painful dystonias, respectively. The score on item 4.2, which asks about the impact of dyskinesias, was rarely above 0 or 1, indicating that the patients had no functional problems from their dyskinesias or that their problems were slight. Nonetheless, it is possible that dyskinesias played a role in generating the scores we used to assess postural instability, especially in patients who were seeking deep brain stimulation surgery; because, presumably, their motor complications have reached an unacceptable state. This fact makes it even more imperative for scales of motor function and postural instability to be validated in the patient population of interest before their widespread clinical adoption. The writers also correctly point out the limitations of the Biodex system in detecting and compensating for dyskinesias when assessing a patient’s risk of falling. This is consistent with our empiric validation of the Biodex measures in predicting the fall risk in these patients and may very likely explain their overall poor performance compared with some other measures in this specific population (many of the Biodex measures we routinely collected in our patient cohort did not correlate at all with falls and were not included in the article describing our system for assessing postural instability). On the question of orthostatic hypotension, those data were not specifically collected; however, patients with “Parkinson’s plus” syndromes were excluded as much as possible given the clinical nature of these diagnoses. We agree that wearables represent a new and exciting development in the monitoring of postural instability and other facets of patient life (such as sleep patterns). Unfortunately, in the population served by our center, there are several barriers to the adoption of wearables in the foreseeable future. Our patients are generally unfamiliar with new technology, and their adoption of it is generally delayed. Furthermore, most patients with Parkinson’s disease in the United States live on a fixed income and rely on medical insurance for expenditures associated with their health care costs. For this reason, it is unlikely that wearable technology will find a large use among this population until a device receives approval from the US Food and Drug Administration for this indication and is a covered expense by Medicare. The goal of our study was to develop and validate a tool for assessing postural instability in patients with Parkinson’s disease who present for deep brain stimulator surgery. The tool we developed, whatever its form, would have to be available now to most community practitioners and patients to be useful for that purpose. We agree that, in the future, the optimal approach would be a clinical evaluation combined with objective, high-quality data that can only be obtained with a wearable device.