Joshua M. Rosenow

Cellular injury and neuroinflammation in children with chronic intractable epilepsy

ObjectiveTo elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery.MethodsCortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussens encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases.ResultsMarked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy.ConclusionsOur results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.

Repetitive transcranial magnetic stimulation-associated neurobehavioral gains during coma recovery

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive method to induce changes in cortical neural excitability. This report presents findings from the first participant of a safety and efficacy study that examined a therapeutic rTMS protocol for persons with severe traumatic brain injury (TBI). OBJECTIVE The primary hypothesis was that there will be no adverse events related to the provision of a 6-week rTMS protocol for persons with severe TBI who remain, at best, in a minimally conscious state for longer than 3 months. The secondary hypothesis was that the rTMS protocol would induce significant neurobehavioral gains during treatment and that these gains would persist at 6-week follow-up. METHODS A 6-week rTMS protocol (30 sessions) was delivered to a 26-year-old man who remained in a vegetative state 287 days after severe TBI. Stimulation was directed over the right dorsolateral prefrontal cortex. Repeated safety measures, neurobehavioral assessments, clinical examinations, and evoked potentials (EP) were obtained at baseline, every fifth rTMS session (weekly), and at a 6-week follow-up. RESULTS There were no adverse events related to the provision of rTMS treatment. A trend toward significant (P = .066) neurobehavioral gains was temporally related to provision of rTMS. Left-sided brain stem auditory EP wave V latencies and waves I to V interpeak latencies improved along with neurobehavioral gains during provision of rTMS, suggesting that improved neural conduction in the pathway mediated the neurobehavioral improvements. CONCLUSIONS Repetitive TMS merits further investigation as a safe therapeutic intervention to alter neural activity, to modulate neural activity, and/or to facilitate recovery in persons with disordered consciousness subsequent to severe TBI.

Recovery of Pain Control by Intensive Reprogramming after Loss of Benefit from Motor Cortex Stimulation for Neuropathic Pain

Introduction: Motor cortex stimulation (MCS) may serve as an adjunct in managing neuropathic pain after other conservative and interventional methods have failed. However, the magnitude and duration of the benefit are highly variable, with a significant percentage of patients losing pain relief over time. We investigated whether intensive reprogramming could recapture the beneficial effects of MCS. Methods: Six patients who had previously undergone MCS implantation for neuropathic pain but had lost benefit were brought back for 1–5 days of intensive reprogramming. Four patients were evaluated as inpatients while the others were seen as outpatients during multiple visits over several days. Several hours a day were spent with each patient. Patients completed visual analog scale (VAS) ratings at intervals throughout the reprogramming period to judge effectiveness of stimulation. Pre- and postadjustment VAS were compared using a paired t test. Results: The patients’ average age was 50 years (range 26–71). The diagnoses were trigeminal neuropathic pain (2 patients), complex regional pain syndrome I (2), phantom limb pain (1) and poststroke pain (1). The mean duration of pain was 6 years. The MCS benefit had initially lasted for a mean of 7.16 months (range 2–18 months). After reprogramming, 5 of 6 patients experienced improvement in pain. Average VAS scores decreased from 7.44 to 2.28 (p < 0.001) in those patients who responded to reprogramming. The average stimulation parameters in these patients were 5 V amplitude (range 1.7–10), 313 µs pulse width (range 240–390) and frequency of 84 Hz (range 55–130). Three patients experienced seizures during reprogramming. The mean seizure threshold was 8.9 V. No patient experienced seizures at their therapeutic settings. Pain control has been maintained after discharge. Conclusion: Intensive reprogramming can recapture the benefit of MCS in patients who have lost pain control. The use of broad dipoles using two contacts rather than one contact of the 1 × 4 electrode array improved the ability to recapture beneficial stimulation. There is a significant risk of seizures during aggressive reprogramming.

Functional Magnetic Resonance Imaging and Optical Imaging for Dominant-hemisphere Perisylvian Arteriovenous Malformations

OBJECTIVE:In this study, we developed an a priori system to stratify surgical intervention of perisylvian arteriovenous malformations (AVMs) in 20 patients. We stratified the patients into three categories based on preoperative functional magnetic resonance imaging (fMRI) language activation pattern and relative location of the AVM. METHODS:In Group I (minimal risk), the AVM was at least one gyrus removed from language activation, and patients subsequently underwent asleep resection. In Group II (high risk), the AVM and language activation were intimately associated. Because the risk of postoperative language deficit was high, these patients were then referred to radiosurgery. In Group III (indeterminate risk), the AVM and language were adjacent to each other. The risk of language deficit could not be predicted on the basis of the fMRI alone. These patients underwent awake craniotomy with electrocortical stimulation mapping and optical imaging of intrinsic signals for language mapping. RESULTS:All patients from Group I (minimal risk) underwent asleep resection without deficit. All Group II (high-risk) patients tolerated radiosurgery without complication. In Group III (indeterminate risk), three patients underwent successful resection, whereas two underwent aborted resection after intracranial mapping. CONCLUSION:We advocate the use of fMRI to assist in the preoperative determination of operability by asleep versus awake craniotomy versus radiosurgery referral. In addition, we advocate the use of all three functional mapping (fMRI, electrocortical stimulation mapping, and optical imaging of intrinsic signals) techniques to clarify the eloquence score of the Spetzler-Martin system before definitive treatment (anesthetized resection versus radiosurgery versus intraoperative resection versus intraoperative closure and radiosurgery referral).

The application accuracy of a skull-mounted trajectory guide system for image-guided functional neurosurgery

Objective: Frameless image guided systems have traditionally been perceived as being less accurate than stereotactic frames, limiting their adoption for trajectory-based procedures such as deep brain stimulator placement which require submillimetric accuracy. However, some studies have suggested that high degrees of accuracy are attainable with optical localization systems. We evaluated the application accuracy of a skull-mounted trajectory guide coupled to an optical image-guided surgery system in a laboratory setting. Materials and Methods: A plastic skull phantom was fitted with five fiducial markers rigidly attached via self-drilling bone screws. Varying MRI and CT imaging protocols were obtained at 25 different centers. A metal disc marked in 1-mm increments was placed at the expected target point. Following registration and alignment of the trajectory guide, radial and depth localization errors were measured. A total of 560 measurements were obtained and detailed statistical analyses were performed. Results: Mean localization error was 1.25 mm with a 95% confidence interval of 2.7 mm and a 99.9% confidence interval of 4.0 mm. These values were significantly lower than those published for the two most widely used frame systems (p<0.001). Conclusions: Accuracy of image-guided localization using a rigid trajectory guide can meet or exceed that achievable with a stereotactic frame.

Direct classification of all American English phonemes using signals from functional speech motor cortex

OBJECTIVE Although brain-computer interfaces (BCIs) can be used in several different ways to restore communication, communicative BCI has not approached the rate or efficiency of natural human speech. Electrocorticography (ECoG) has precise spatiotemporal resolution that enables recording of brain activity distributed over a wide area of cortex, such as during speech production. In this study, we sought to decode elements of speech production using ECoG. APPROACH We investigated words that contain the entire set of phonemes in the general American accent using ECoG with four subjects. Using a linear classifier, we evaluated the degree to which individual phonemes within each word could be correctly identified from cortical signal. MAIN RESULTS We classified phonemes with up to 36% accuracy when classifying all phonemes and up to 63% accuracy for a single phoneme. Further, misclassified phonemes follow articulation organization described in phonology literature, aiding classification of whole words. Precise temporal alignment to phoneme onset was crucial for classification success. SIGNIFICANCE We identified specific spatiotemporal features that aid classification, which could guide future applications. Word identification was equivalent to information transfer rates as high as 3.0 bits s(-1) (33.6 words min(-1)), supporting pursuit of speech articulation for BCI control.

Application accuracy of an electromagnetic field-based image-guided navigation system

Objective: We tested the application accuracy of an electromagnetic field-based image guidance system to compare it to traditional optically tracked systems. Methods: A plastic skull phantom was fitted with fiducial markers rigidly attached via self-drilling bone screws. Volumetric CT scan was obtained to simulate the clinical condition. A metal disc marked in 1-mm increments was placed at the expected target point. Following registration and alignment of a trajectory guide, radial and depth localization errors were measured after both freehand and stabilized approaches on both the right and left sides. Statistical analyses of the localization errors were performed. Results: Total target localization error ranged from 0.71 to 3.51 mm with a mean ± SEM of 2.13 ± 0.11 mm. The radial error averaged 0.98 ± 0.11 mm, depth error 1.74 ± 0.13 mm. The freehand procedures produced a statistically greater radial, depth and total error than the fixed procedures. Conclusions: Accuracy of image-guided localization using an electromagnetic field guidance system is similar to that reported for optically guided systems.

Utility of brain biopsy in patients with acquired immunodeficiency syndrome before and after introduction of highly active antiretroviral therapy.

OBJECTIVE This study investigates the changing indications, results, and practice patterns of brain biopsy in patients with acquired immunodeficiency syndrome (AIDS) as treatment evolved with the development of highly active antiretroviral therapy (HAART). METHODS We collected data on 246 patients with AIDS who were undergoing brain biopsy of intracranial lesions. Patients were managed in accordance with a uniform protocol. Patients were divided into two groups of those biopsied in the era before (1992–1996) or after (1997–2001) the use of HAART. RESULTS The introduction of HAART led to a steep decrease in the number of biopsies performed annually. The protocol functioned well. Diagnoses were obtained for 92.3% of patients. Lymphoma was the most frequent diagnosis (52.9% of patients), followed by progressive multifocal leukoencephalopathy (18.9% of patients) and toxoplasmosis (8.1% of patients). No patient who underwent lesion biopsy for reasons of negative toxoplasmosis titers or atypical radiology evaluation was diagnosed with toxoplasmosis. Nineteen patients who experienced failed toxoplasmosis treatment were diagnosed with toxoplasmosis. Toxoplasmosis titers had a high specificity and a negative predictive value. Patients with progressive multifocal leukoencephalopathy or nondiagnostic biopsies were more likely to have solitary lesions. The average Karnofsky performance score at the time of biopsy was 72.4, which is still within the range of independent functioning. Significant intracerebral hemorrhages were only observed in patients with lymphoma who also had low platelet counts. CONCLUSION Although the number of patients with AIDS who require brain biopsy has decreased, the procedure still has merits. The paradigm we developed was useful for selecting patients for early biopsy. Patients with AIDS who also have intracerebral lesions should have toxoplasmosis titers performed, and those whose titers are negative for toxoplasmosis should undergo early brain biopsy.

Impact of resident involvement in neurosurgery: an analysis of 8748 patients from the 2011 American College of Surgeons National Surgical Quality Improvement Program database

OBJECT This study evaluates the impact of resident presence in the operating room on postoperative outcomes in neurosurgery. METHODS The authors retrospectively reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and identified all cases treated in a neurosurgery service in 2011. Propensity scoring analysis and multiple logistic regression models were used to reduce patient bias and to assess independent effect of resident involvement. RESULTS Of the 8748 neurosurgery cases identified, residents were present in 4529 cases. Residents were more likely to be involved in complex procedures with longer operative duration. The multivariate analysis found that resident involvement was not a statistically significant factor for overall complications (OR 1.116, 95% CI 0.961-1.297), surgical complications (OR 1.132, 95% CI 0.825-1.554), medical complications (OR 1.146, 95% CI 0.979-1.343), reoperation (OR 1.250, 95% CI 0.984-1.589), mortality (OR 1.164, 95% CI 0.780-1.737), or unplanned readmission (OR 1.148, 95% CI 0.946-1.393). CONCLUSIONS In this multicenter study, the authors demonstrated that resident involvement in the operating room was not a significant factor for postoperative complications in neurosurgery service. This analysis also showed that much of the observed difference in postoperative complication rates was attributable to other confounding factors. This is a quality indicator for resident trainees and current medical education. Maintaining high standards in postgraduate training is imperative in enhancing patient care and reducing postoperative complications.

ACR Appropriateness Criteria Low Back Pain.

Most patients presenting with uncomplicated acute low back pain (LBP) and/or radiculopathy do not require imaging. Imaging is considered in those patients who have had up to 6 weeks of medical management and physical therapy that resulted in little or no improvement in their back pain. It is also considered for those patients presenting with red flags raising suspicion for serious underlying conditions, such as cauda equina syndrome, malignancy, fracture, and infection. Many imaging modalities are available to clinicians and radiologists for evaluating LBP. Application of these modalities depends largely on the working diagnosis, the urgency of the clinical problem, and comorbidities of the patient. When there is concern for fracture of the lumbar spine, multidetector CT is recommended. Those deemed to be interventional candidates, with LBP lasting for > 6 weeks having completed conservative management with persistent radiculopathic symptoms, may seek MRI. Patients with severe or progressive neurologic deficit on presentation and red flags should be evaluated with MRI. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (the RAND/UCLA Appropriateness Method and the Grading of Recommendations Assessment, Development, and Evaluation) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.