Molly E. Hubbard

Multiple calcifying pseudoneoplasms of the neuraxis

Calcified pseudoneoplasms of the neuraxis (CAPNON) are a rare diagnostic entity. They have been reported intra‐cranially as well as in the spine, and are most commonly found at the skull base. This is a case report of a 38‐year‐old woman who presented with bilateral CAPNON, diagnosed 8 years apart. While there are approximately 46 reported in the current literature of cerebral and spinal fibro‐osseous lesions, this is the first report of separate lesions.

Transfundal stent placement for treatment of complex basilar tip aneurysm: technical note.

We describe a case where a complex unruptured basilar tip aneurysm was treated with a unique method of stent-assisted coil embolization. The aneurysm was considered to have a complex anatomy since both the left posterior cerebral artery and left superior cerebellar artery originated from the dome of the aneurysm. Also, the right posterior cerebral artery was incorporated in the aneurysm neck and needed to be protected prior to coil embolization. This case describes placement of a stent across the span of the aneurysm fundus in order to preserve the two branches arising from it, and the aneurysm dome was coiled without any complication. Using modifications of existing strategies for stent-assisted coil embolization, the aneurysm was treated without any complications and all of the vessels at risk were preserved.

Increase in brain atrophy after subdural hematoma to rates greater than associated with dementia

OBJECTIVEChronic subdural hematoma (cSDH) is a highly morbid condition associated with brain atrophy in the elderly. It has a reported 30% 1-year mortality rate. Approximately half of afflicted individuals report either no or relatively unremarkable trauma preceding their diagnosis, raising the possibility that cSDH is a manifestation of degenerative or inflammatory disease rather than trauma. The purpose of this study was to compare the rates of cerebral atrophy before and after cSDH to determine whether it is more likely that cSDH causes atrophy or that atrophy causes cSDH. The authors also compared atrophy rates in patients with cSDH to the rates in patients with and without dementia.METHODSThe authors developed algorithmic segmentation analysis software to measure whole-brain, CSF, and intracranial space volumes. They then identified military veterans who had undergone at least 4 brain CT scans over a period of 10 years. Within this database, the authors identified 146 patients with 962 head CT scans who had received diagnoses of either cSDH, dementia, or no known dementia condition. Volumetric analyses of brains in 45 patients with dementia (dementia group) and 73 patients without dementia (nondementia group), in whom 262 and 519 head CT scans were obtained, respectively, were compared with 11 patients in whom 81 CT scans were obtained a mean of 4.21 years before a cSDH diagnosis and 17 patients in whom 100 scans were obtained a mean of 4.24 years after SDH. Longitudinal measures were then related to disease status and the time since first scan by using hierarchical models, and atrophy rates between the groups were compared.RESULTSHead CT scans from patients were obtained for an average time period of 4.21 years (SD 1.69) starting at a mean patient age of 74 years. Absolute brain volume loss for the 17 patients in the post-SDH group (13 were treated surgically) was significantly greater, at 16.32 ml/year, compared with 6.61 ml/year in patients with dementia, 5.33 ml/year in patients without dementia, and 3.57 ml/year in pre-SDH patients. The atrophy rate for these individuals prior to enrollment in the study was 2.32 ml/year (p = 0.001). In terms of brain volume normalized to cranial cavity size, the post-SDH group had an atrophy rate of 0.7801%/year, compared with 0.4467%/year in patients with dementia, 0.3474%/year in patients without dementia, and 0.2135%/year in the pre-SDH group.CONCLUSIONSPrior to development of a cSDH, the atrophy rates in patients who ultimately develop cSDH are similar to those of patients without dementia. After development of a cSDH, the atrophy rates increase to more than twice those of patients with dementia. Chronic subdural hematoma is thus associated with a significant increase in brain atrophy rate. These findings suggest the neurotoxic consequences of cSDH and may have implications for better understanding of the pathophysiology of cerebral atrophy and dementia.

Naturally Occurring Canine Glioma as a Model for Novel Therapeutics

Abstract Background: Current animal models of glioma are limited to small animal models, which are less predictive of treatment of human disease. Canines often develop gliomas de novo, but the natural history of the disease is not well described. Objective: We provide data for naturally occurring canine gliomas; evaluating medical and surgical therapies. Methods: We reviewed medical records of pet dogs with a presumptive diagnosis of glioma from MRI imaging that underwent surgery as part of the Canine Brain Tumor Clinical Trials Program. Breed, age, sex, median progression-free, and overall survival times and cause of death were recorded for multivariate analysis. Results: Ninety five dogs (56 male; mean age = 8.3 years) were included, but nine were excluded as final pathology was non-neoplastic. Gross total resection was reported in 81 cases based on postoperative MRI. Seventy had high-grade tumors (grade III or IV). Eighty three dogs presented with seizures, being the most common presenting clinical sign. Median survival after surgery was 723 days (95% CI 343–1103) for grade II tumors, 301 days (197–404) for grade III and 200 days (126–274) for grade IV (p = .009 Kaplan–Meier survival analysis; Log Rank test). Age (cox regression, p = .14) or sex (Kaplan–Meier test, p = .22) did not predict survival. Conclusions: This study establishes normative data for a model exploiting dogs with naturally occurring glioma, which can be used to test novel therapies prior to translation to human trials. Further work will focus on the effects of different therapies, including chemotherapy, radiation therapy, and immunotherapy.

Assessment of acute head injury in an emergency department population using sport concussion assessment tool – 3rd edition

ABSTRACT Sport Concussion Assessment Tool version 3 (SCAT-3) is one of the most widely researched concussion assessment tools in athletes. Here normative data for SCAT3 in nonathletes are presented. The SCAT3 was administered to 98 nonathlete healthy controls, as well as 118 participants with head-injury and 46 participants with other body trauma (OI) presenting to the ED. Reference values were derived and classifier functions were built to assess the accuracy of SCAT3. The control population had a mean of 2.30 (SD = 3.62) symptoms, 4.38 (SD = 8.73) symptom severity score (SSS), and 26.02 (SD = 2.52) standardized assessment of concussion score (SAC). Participants were more likely to be diagnosed with a concussion (from among healthy controls) if the SSS > 7; or SSS ≤ 7 and SAC ≤22 (sensitivity = 96%, specificity = 77%). Identification of head injury patients from among both, healthy controls and body trauma was possible using rule SSS > 7 and headache or pressure in head present, or SSS ≤ 7 and SAC ≤ 22 (sensitivity = 87%, specificity = 80%). In this current study, the SCAT-3 provided high sensitivity to discriminate acute symptoms of TBI in the ED setting. Individuals with a SSS > 7 and headache or pressure in head, or SSS ≤ 7 but with a SAC ≤ 22 within 48-hours of an injury should undergo further testing.

Poster 75: Headache Prevalence 30 Years After Severe Traumatic Brain Injury (TBI): Results From a Comparative Cohort Study

Disclosures: Jacob Moore: I Have No Relevant Financial Relationships To Disclose Objective: To develop predictive scales in pediatric patients with Charcot-Marie-Tooth (CMT) that correlate changes in the CharcotMarie-Tooth neuropathy score (CMTNS) with type of ambulatory aid used. Design: This is a retrospective cross-sectional study. Data collected included demographics, CMTNS, type of ambulatory aid used, foot surgery, difficulty with buttons, and difficulty with eating utensils. Mean scores and standard deviations for CMTNS were calculated for every ambulatory aid used to develop predictive scales. Setting: An integrated group of academic medical centers. Participants: 625 patients, 270 male and 269 female, who were consented through the Inherited Neuropathy Consortium as part of the natural history clinical registry trial [NCT01193075] were assessed in this study, and of these, 539 were included in the analysis. Mean age was 13 years old, range 8-18, SD 2.9. 84% of the patients were Caucasian. Interventions: Not applicable. Main Outcome Measures: Not applicable. Results: There was a strong correlation between ambulatory aid used and CMTNS score (0.63, p < .0001); smaller correlations were seen between ambulatory aid used and foot surgery (0.16, p 1⁄4.007), buttons (0.31, p < .0001) and eating utensils (0.33, p < .0001). No ambulatory aid use and minimal (shoe inserts, custom shoes, nightsplints) ambulatory aid use had equivalent mean CMTNS at 8.4. Mean CMTNS for use of one or more of the following ambulatory aids: supramalleolar orthosis (SMO), supramalleolar ankle foot orthosis (SMAFO), ankle foot orthosis (AFO), molded ankle foot orthotics (MAFO), Arizona brace was calculated at 10.5. Mean CMTNS for using a wheelchair or scooter was 23. Conclusions: We have identified predictive scales that correlate CMTNS values with progressive functional needs. We recommend prospective validation of our predictive scales in a CMT clinic population. Level of Evidence: Level II

Elevated intracranial pressure and reversible eye-tracking changes detected while viewing a film clip

OBJECTIVE The precise threshold differentiating normal and elevated intracranial pressure (ICP) is variable among individuals. In the context of several pathophysiological conditions, elevated ICP leads to abnormalities in global cerebral functioning and impacts the function of cranial nerves (CNs), either or both of which may contribute to ocular dysmotility. The purpose of this study was to assess the impact of elevated ICP on eye-tracking performed while patients were watching a short film clip. METHODS Awake patients requiring placement of an ICP monitor for clinical purposes underwent eye tracking while watching a 220-second continuously playing video moving around the perimeter of a viewing monitor. Pupil position was recorded at 500 Hz and metrics associated with each eye individually and both eyes together were calculated. Linear regression with generalized estimating equations was performed to test the association of eye-tracking metrics with changes in ICP. RESULTS Eye tracking was performed at ICP levels ranging from -3 to 30 mm Hg in 23 patients (12 women, 11 men, mean age 46.8 years) on 55 separate occasions. Eye-tracking measures correlating with CN function linearly decreased with increasing ICP (p < 0.001). Measures for CN VI were most prominently affected. The area under the curve (AUC) for eye-tracking metrics to discriminate between ICP < 12 and ≥ 12 mm Hg was 0.798. To discriminate an ICP < 15 from ≥ 15 mm Hg the AUC was 0.833, and to discriminate ICP < 20 from ≥ 20 mm Hg the AUC was 0.889. CONCLUSIONS Increasingly elevated ICP was associated with increasingly abnormal eye tracking detected while patients were watching a short film clip. These results suggest that eye tracking may be used as a noninvasive, automatable means to quantitate the physiological impact of elevated ICP, which has clinical application for assessment of shunt malfunction, pseudotumor cerebri, concussion, and prevention of second-impact syndrome.

Thoracic spinal cord impingement by an arachnoid web at the level of a hemivertebra: case report

Congenital scoliosis due to a hemivertebra requires surgical stabilization prior to skeletal maturity if rapidly progressive curve growth occurs. Here the authors present the unique case of a man who, at the age of 12 years, had undergone Harrington rod placement for stabilization of progressive congenital scoliosis due to a T-11 hemivertebra and then, at the age of 53 years, presented with acutely progressive myelopathy due to spinal cord compression from an arachnoid web at T-11 despite a solid fusion mass at the prior surgical site. The patient underwent a posterior midline approach for resection of the T-11 pedicle at the level of the hemivertebra, intradural spinal cord detethering with resection of the arachnoid web at T-11, and T2-L2 instrumented fusion with deformity correction, leading to subsequent resolution of his acute myelopathic symptoms. In conclusion, arachnoid web formation superimposed on preexisting tension on the thoracic spinal cord from congenital scoliosis due to a T-11 hemivertebra caused acute myelopathy in an adult with a previously solid fusion mass from childhood. The resolution of acute myelopathy and halting of further progression occurred with pedicle resection, arachnoid web fenestration, and spinal deformity correction.

Effect of Gamma Knife Radiosurgery and Programmed Cell Death 1 Receptor Antagonists on Metastatic Melanoma

Learning objectives To evaluate radiation-induced changes in patients with brain metastasis secondary to malignant melanoma who received treatment with Gamma Knife radiosurgery (GKRS) and programmed cell death 1 (PD-1) receptor antagonists. Introduction Stereotactic radiosurgery and chemotherapeutics are used together for treatment of metastatic melanoma and have been linked to delayed radiation-induced vasculitic leukoencephalopathy (DRIVL). There have been reports of more intense interactions with new immunotherapeutics targeting PD-1 receptors, but their interactions have not been well described and may result in an accelerated response to GKRS. Here we present data on subjects treated with this combination from a single institution. Methods Records from patients who underwent treatment for metastatic melanoma to the brain with GKRS from 2011 to 2016 were reviewed. Demographics, date of brain metastasis diagnosis, cause of death when applicable, immunotherapeutics, and imaging findings were recorded. The timing of radiation therapy and medications were also documented. Results A total of 79 subjects were treated with GKRS, and 66 underwent treatment with both GKRS and immunotherapy. Regarding the 30 patients treated with anti-PD-1 immunotherapy, 21 patients received pembrolizumab, seven patients received nivolumab, and two patients received pembrolizumab and nivolumab. Serial imaging was available for interpretation in 25 patients, with 13 subjects who received GKRS and anti-PD-1 immunotherapy less than six weeks of each other. While four subjects had indeterminate/mixed findings on subsequent magnetic resonance imaging (MRI), nine subjects were noted to have progression. Two of these patients showed progression but subsequent imaging revealed a decrease in progression or improvement on MRI to previously targeted lesions by GKRS. None of the 13 subjects had surgery following their combined therapies. Conclusions This data suggests that there is need for further investigation of the role for concurrent treatment with PD-1 inhibitors and GKRS to enhance the treatment of metastatic melanoma. We present data on 13 patients who appear to have some radiologic benefit to this treatment combination, two of whom had radiographic pseudoprogression.

Diagnosing Traumatic Encephalopathy Syndrome

be noted that all measurements of partial brain tissue oxygen tension were 16 mm Hg or greater and no brain around the partial brain tissue oxygen tension probes met criteria for either type of oxidative metabolism impairment. It seems that an alternative explanation could be offered for the inability to augment OEF, and that would be uncoupling hypoxia resulting from primary mitochondrial failure.3 Areas exhibiting primary mitochondrial failure may produce a similar tissue signature with reduced CMRO2, cerebral blood flow, and a nonaugmenting OEF. It is interesting to know whether these 2 different states, diffusion limitation (diffusion hypoxia) vs mitochondrial failure (uncoupling hypoxia), could be further distinguished based on imaging and/or neuromonitoring tools. Using microdialysis, it has been reported that an increased lactate-pyruvate ratio with preserved vs reduced pyruvate could hint toward mitochondrial failure as the predominant mechanism.4 It would have been further informative if participants of this study had microdialysis catheters to correlate cytoplasmic redox biochemical data (lactate, pyruvate, lactate-pyruvate ratio, and tissue pH) with PET data. Selective inhibition of mitochondrial function has been also used in animal models to investigate tissue oxygen utilization and metabolism patterns in primary mitochondrial failure. The ability to differentiate can have clinical implications because hyperoxia has been proposed as a way to overcome diffusion limitation, whereas mitochondrial failure could be a target for novel neurotherapeutics. Additionally, based on potential adverse effects of hyperoxia, knowledge of the pattern would allow for selective and targeted use.