An unusual cause of shunt failure requiring multidisciplinary treatment.

Rarer etiologies of shunt malfunction may be difficult to detect, can present insidiously, and often require a multidisciplinary approach to safely and effectively address.

Safety and interim survival data after intracranial administration of M032, a genetically engineered oncolytic HSV-1 expressing IL-12, in pet dogs with sporadic gliomas.

OBJECTIVE: The diagnosis of glioma remains disheartening in the clinical realm. While a multitude of studies and trials have shown promise, improvements in overall survival have been disappointing. Modeling these tumors in the laboratory setting has become increasingly challenging, given their complex in situ behavior and interactions for therapeutic evasion. Dogs, particularly brachycephalic breeds, are known to spontaneously develop gliomas that resemble human gliomas both clinically and pathophysiologically, making canines with sporadic tumors promising candidates for study. Typically, survival among these dogs is approximately 2 months with palliation alone. METHODS: The authors have completed the first stage of a unique phase I dose-escalating canine clinical trial in which the safety and tolerability of M032, a nonneurovirulent oncolytic herpes simplex virus-1 vector genetically engineered to express interleukin-12, are being studied in pet dogs with gliomas undergoing maximum safe tumor resection and inoculation of the cavity with the viral infusate. RESULTS: Twenty-five canine patients were enrolled between January 2018 and August 2020. One patient was electively withdrawn from the trial by its owner, and 3 did not receive the virus. For the 21 dogs that remained, 13 had high-grade gliomas, 5 had low-grade gliomas, and 3 were undetermined. According to histopathological analysis, 62% of the tumors were oligodendrogliomas. At the time of this report, the median overall survival from the date of treatment was 151 days (± 78 days). No significant adverse events attributable to M032 or dose-limiting toxicities have been observed to date. CONCLUSIONS: In this largest study of oncolytic viral therapy for canine brain tumors to date, treatment with M032 did not cause harm and the combination of surgery and oncolytic viral therapy may have contributed to prolonged survival in pet dogs with spontaneous gliomas. Forthcoming in-depth radiographic, immunohistochemical, and genetic analyses will afford a more advanced understanding of how this treatment impacts these tumors and the immune system. Our goal is to utilize these findings bitranslationally to inform human studies and refine therapies that will improve outcomes in both humans and pet dogs with gliomas.

Posterior communicating artery injury and symptomatic vasospasm after high-energy blunt head injury: illustrative case.

BACKGROUND: Most of the published literature pertaining to blunt traumatic cerebrovascular injury (BCVI) is focused on extracranial arterial injury. Studies of intracranial arterial injury are relatively uncommon. OBSERVATIONS: The clinical course of a patient who sustained an injury to the right posterior communicating artery followed by infarction due to vasospasm after severe traumatic brain injury is presented, along with a focused literature review. LESSONS: Intracranial BCVI is uncommon, and this report may serve to raise awareness of BCVI management and the importance of recognizing symptomatic vasospasm due to BCVI.

Rapid Evolution and Rupture of an Incidental Aneurysm During Hyperdynamic Therapy for Cerebral Vasospasm.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. Among the most common sequelae of aSAH is delayed cerebral ischemia. Hyperdynamic therapy (fluid supplementation and hypertension) is used to increase cerebral perfusion. However, the safety of hyperdynamic therapy in patients with separate unruptured, unsecured intracranial aneurysms is not well-established. Herein, a rare case demonstrating the rapid evolution and rupture of an incidental unsecured aneurysm in the setting of hyperdynamic therapy is presented. CASE DESCRIPTION: A 56-year-old woman without significant medical history presented with aSAH secondary to rupture of a 3-mm left posterior inferior cerebellar artery aneurysm. After endovascular treatment of this aneurysm, she developed symptomatic vasospasm prompting initiation of hyperdynamic therapy. Seven days after initiation of hyperdynamic therapy, she experienced rupture of an incidental pericallosal artery aneurysm that was found to have increased in size during the hyperdynamic therapy. She ultimately survived and was functionally independent approximately 1 year after her initial ictus. CONCLUSIONS: This case demonstrates that enlargement and rupture of an incidental, previously unruptured aneurysm may occur during hyperdynamic therapy.

Upward transtentorial herniation.

While subfalcine, transtentorial, and transmagnal herniation are most often thought of as downward phenomena, brain herniation can also occur in the upward direction with similarly disastrous clinical consequences.

The One Health Consortium: Design of a Phase I Clinical Trial to Evaluate M032, a Genetically Engineered HSV-1 Expressing IL-12, in Combination With a Checkpoint Inhibitor in Canine Patients With Sporadic High Grade Gliomas.

As the most common and deadly of primary brain tumors, malignant gliomas have earned their place within one of the most multifaceted and heavily-funded realms of medical research. Numerous avenues of pre-clinical investigation continue to provide valuable insight, but modeling the complex evolution and behavior of these tumors within a host under simulated circumstances may pose challenges to extrapolation of data. Remarkably, certain breeds of pet dogs spontaneously and sporadically develop high grade gliomas that follow similar incidence, treatment, and outcome patterns as their human glioma counterparts. The most malignant of these tumors have been refractory to limited treatment options despite aggressive treatment; outcomes are dismal with median survivals of just over 1 year in humans and 2 months in dogs. Novel treatments are greatly needed and combination therapies appear to hold promise. This clinical protocol, a dose-escalating phase I study in dogs with sporadic malignant glioma, represents a first in comparative oncology and combination immunotherapy. The trial will evaluate M032, an Interleukin-12 expressing Herpes Simplex virus, alone and combined with a checkpoint inhibitor, Indoximod. Extensive pre-clinical work has demonstrated safety of intracranial M032 administration in mice and non-human primates. M032 is currently being tested in humans with high-grade malignant gliomas. Thus, in a novel fashion, both canine and human trials will proceed concurrently allowing a direct "head-to-head" comparison of safety and efficacy. We expect this viral oncolytic therapy to be as safe as it is in human patients and M032 to (a) infect and kill glioma cells, producing a virus and tumor cell antigen-rich debris field; (b) provide an adjuvant effect due to liberation of viral DNA, which is rich in unmethylated CpG sequences that "toggle" TLR-9 receptors; and (c) express IL-12 locally, stimulating induction of TH1 lymphocytes. The resultant immune-mediated anti-viral responses should, through cross-epitope spreading, translate into a strong response to tumor antigens. The ability to compare human and dog responses in real time affords the most stringent test of suitability of the dog as an informative model of human brain tumors. Subsequent studies will allow canine trials to properly inform the design of human trials.

Incidence and risk factors for seizures associated with deep brain stimulation surgery.

OBJECTIVE: The objective of this study was to determine the incidence of seizures following deep brain stimulation (DBS) electrode implantation and to evaluate factors associated with postoperative seizures. METHODS: The authors performed a single-center retrospective case-control study. The outcome of interest was seizure associated with DBS implantation. Univariate analyses were performed using the Student t-test for parametric continuous outcomes. The authors used the Kruskal-Wallis test or Wilcoxon rank-sum test for nonparametric continuous outcomes, chi-square statistics for categorical outcomes, and multivariate logistic regression for binomial variables. RESULTS: A total of 814 DBS electrode implantations were performed in 645 patients (478 [58.7%] in men and 520 [63.9%] in patients with Parkinson's disease). In total, 22 (3.4%) patients who had undergone 23 (2.8%) placements experienced seizure. Of the 23 DBS implantation-related seizures, 21 were new-onset seizures (3.3% of 645 patients) and 2 were recurrence or worsening of a prior seizure disorder. Among the 23 cases with postimplantation-related seizure, epilepsy developed in 4 (17.4%) postoperatively; the risk of DBS-associated epilepsy was 0.50% per DBS electrode placement and 0.63% per patient. Nine (39.1%) implantation-related seizures had associated postoperative radiographic abnormalities. Multivariate analyses suggested that age at surgery conferred a modest increased risk for postoperative seizures (OR 1.06, 95% CI 1.02-1.10). Sex, primary diagnosis, electrode location and sidedness, and the number of trajectories were not significantly associated with seizures after DBS surgery. CONCLUSIONS: Seizures associated with DBS electrode placement are uncommon, typically occur early within the postoperative period, and seldom lead to epilepsy. This study suggests that patient characteristics, such as age, may play a greater role than perioperative variables in determining seizure risk. Multiinstitutional studies may help better define and mitigate the risk of seizures after DBS surgery.

Cerebellar Arteriovenous Malformation Rupture Despite Apparent Angiographic Obliteration.

BACKGROUND: Arteriovenous malformations (AVMs) can occur in all regions of the brain and spinal cord, with clinical consequences and risks varying by location. Delayed AVM rupture despite digital subtraction angiography-confirmed obliteration post-radiation is exceedingly rare. CASE DESCRIPTION: To our knowledge, we present the first documented case of delayed hemorrhage associated with a cerebellar AVM 5 years after linear accelerator-based radiation in a man aged 31 years despite apparent angiographic obliteration. CONCLUSIONS: Intracranial hemorrhage after radiosurgery in digital subtraction angiography-confirmed obliterated AVMs is rare, with limited understanding of risk factors, appropriate preventative management, and mechanisms of occurrence. This case serves to demonstrate the need for greater awareness of this rare complication, as well as the need for appropriate surveillance and management strategies.

Patient Satisfaction in Surgery for Parkinson's Disease: A Systematic Review of the Literature.

The objective of the study was to establish how patient satisfaction with surgical treatment of Parkinson's disease (PD) has been previously measured, determine whether an ideal patient satisfaction instrument exists, and to define the dimensions of care that determine patient satisfaction with the surgical treatment of PD. A systematic search of four online databases, unpublished sources, and citations was undertaken to identify 15 studies reporting patient satisfaction with the surgical treatment of PD. Manuscripts were reviewed and instruments were categorized by content and method axes. One study was found to utilize two distinct patient satisfaction instruments, which brought the total number of satisfaction instruments assessed to 16. Major factors influencing patient satisfaction were identified and served as a structure to define the dimensions of patient satisfaction in the surgical treatment of PD. Studies used predominantly multidimensional (10/16), rather than global (6/16) satisfaction instruments. Generic (12/16) rather than disease-specific (4/16) instruments were utilized more frequently. Every study reported on satisfaction with outcome and four studies reported on satisfaction with outcome and care. Six dimensions of patient status, outcome and care experience affecting patient satisfaction were identified: motor function, patient-specific health characteristics, programming/long-term care, surgical considerations, device/hardware, and functional independence.  At present, no patient satisfaction instrument exists that is disease-specific and covers all dimensions of patient satisfaction in surgery for PD. For quality improvement, such a disease-specific, comprehensive patient satisfaction instrument should be designed, and, if demonstrated to be reliable and valid, widely implemented.

Le Coup de Poignard Rachidien: A Historical Perspective.

A spinal subarachnoid hemorrhage (SAH) is uncommon. One of the earliest detailed analyses of a spinal SAH was in 1928 by the French physician Paul Michon, who coined the term "le coup de poignard rachidien" to describe the pathognomonic, intense spinal pain experienced by patients with spinal SAH, equating it to being stabbed by a dagger. Michon sub-classified spinal SAH into the upper and lower forms, pointing out that the stabbing spinal pain is more characteristic of SAH in the cervical and thoracic regions and especially in the interscapular region. Translation and subsequent analysis of Michon's original French paper published in La Presse Medicale in 1928 shed light on two cases in which patients presented with le coup de poignard rachidien and signs of spinal cord dysfunction but little, if any, intracranial symptoms. The patients both showed symptomatic relief following therapeutic lumbar puncture. Later, authors have questioned the notion that intense spinal or interscapular pain is mandatory in the diagnosis of spinal SAH and have additionally provided evidence contrary to Michon's assertion that intracranial symptoms, if any, occur later in the progression of spinal SAH and are largely insignificant.

Seizure outcomes after stereotactic radiosurgery for the treatment of cerebral arteriovenous malformations.

OBJECTIVE Patients with cerebral arteriovenous malformations (AVMs) commonly present with seizure. Seizure outcomes in patients treated with stereotactic radiosurgery (SRS) are poorly defined. A case series of patients with cerebral AVMs treated with SRS is presented to evaluate long-term seizure outcome. METHODS A retrospective review of the medical record was performed, identifying 204 consecutive patients with AVMs treated with SRS between January 1991 and June 2012. Clinical and radiographic data were evaluated. Seizure outcome was measured using the Engel Epilepsy Surgery Outcome Scale. Mean duration of follow-up was 37.1 months (SD 38.3 months) with a minimum follow-up period of 1 month. RESULTS Of the 204 patients with cerebral AVMs treated with SRS, 78 patients (38.2%) presented with seizures and 49 of those patients were treated with antiepileptic drugs (AEDs). Following SRS, 63 (80.8%) of the 78 patients who had had seizures prior to SRS were seizure-free at a mean follow-up time of 37.2 months (SD 41.3 months). Of the 49 patients who had been treated with AEDs, 17 were still taking AEDs at last follow-up. Of the 126 patients who did not present with seizures prior to treatment with SRS, only 5 patients (4.0%) had seizures in the post-SRS period. There was no significant correlation between post-SRS seizure status and patient demographic features, comorbidities, AVM characteristics, history of operative intervention, pre- or posttreatment hemorrhage, or radiographic degree of AVM resolution. CONCLUSIONS Stereotactic radiosurgery for treatment of cerebral AVMs is effective at providing long-term control of seizures. A substantial number of patients who were treated with SRS were not only seizure free at their last follow-up, but had been successfully weaned from antiepileptic medications.

Assessment of driving outcomes after epilepsy surgery.

INTRODUCTION: Driving is an important factor contributing to good quality of life in patients with epilepsy. Little work has been undertaken to explore the details of driving experience alone in this patient population. We assessed the driving status of our patients prior to and following surgery for epilepsy. We also sought to determine what associations exist between patient characteristics and postoperative driving status. METHODS: The participants were selected from those adult patients with epilepsy who have required surgical treatment at our home institution between 2006 and 2010. Each participant received a questionnaire asking about driving and seizure status before and after surgery. The surveys were distributed using a modified Dillman approach. Perioperative patient data were obtained from the electronic medical record system in addition to a previously assembled epilepsy database from the Neurology Department at our institution. Independent variables were analyzed to look for significant associations with driving outcomes. RESULTS: One hundred forty eligible patients were included in the survey population; 78 patients returned a questionnaire for a response rate of 55.7%. Eighty percent of patients experienced driving as a regular part of life at some point prior to surgery. At the time of the questionnaire distribution, 68% of patients had returned to regular driving. Demographic characteristics did not play a significant role in whether or not the patient had a favorable driving outcome after surgery. However, patients who had a history of driving on a regular basis prior to surgery and those who had an Engel Class I outcome after surgery had significantly higher rates of good driving outcomes. Also, patients with an unfavorable preoperative driving status were more likely to have a favorable driving outcome after surgery if they had an Engel Class I outcome. Patients in whom intracranial electroencephalography (EEG) was utilized prior to resection had worse driving outcomes. CONCLUSIONS: A surprisingly high percentage of patients with epilepsy have experienced driving on a regular basis prior to surgery. We can assume that most patients were not driving immediately prior to surgery, given the fact that they had progressed to requiring surgery for treatment of their epilepsy. Thus, a driving rate of 68% after surgery can be considered good. We found that a patient's preoperative driving history, the use of intracranial EEG before surgical resection, and Engel classification were significant predictors of postoperative driving outcomes. These data provide patients with assistance in preoperative counseling. More investigation needs to be completed in other patient variables - such as seizure types, magnetic resonance imaging (MRI) findings, and patient motivators for driving - as possible predictors of driving outcomes.

The nonsurgical nature of patients with subarachnoid or intraparenchymal hemorrhage associated with mild traumatic brain injury.

OBJECT: Mild traumatic brain injury (mTBI), as defined by Glasgow Coma Scale (GCS) score of 13 or higher, is a common problem in the United States and worldwide, estimated to affect more than 1 million patients yearly. When associated with intracranial hemorrhage, it is a common reason for neurosurgical consultation and transfer to tertiary care centers. The authors set out to investigate the clinical implications of subarachnoid hemorrhage (SAH) and/or intraparenchymal hemorrhage (IPH) associated with mTBI in hopes of standardization of mTBI clinical care and optimization of resource allocation. METHODS: The authors performed a retrospective review of 500 consecutively treated patients with mTBI and SAH and/or IPH admitted to a Level I trauma center in Alabama between May 2003 and May 2013. They performed a review of medical records to confirm the diagnosis, determine neurological condition at admission, and assess for episodes of neurological decline or brain injury-related complications including altered mental status, seizures, and hyponatremia. RESULTS: Of the 500 patients for whom data were reviewed, 304 (60.8%) were male and 196 (39.2%) were female. Average age was 46.3 years. Overall, 63 patients (12.6%) had isolated IPH, 411 (82.2%) had isolated SAH, and 26 (5.2%) had radiographic evidence of both IPH and SAH. One hundred forty-five patients (29%) were transferred an average distance of 64.5 miles. The authors identified no patients who experienced neurological worsening during their hospital course. Two patients experienced hyponatremia that required treatment with sodium supplementation. CONCLUSIONS: Patients with the constellation of SAH and/or IPH and mTBI do not require neurosurgical consultation, and these findings should not be used as the sole criteria to justify transfer to tertiary referral centers.