Post-partum posterior reversible encephalopathy syndrome requiring decompressive craniectomy: case report and review of the literature.

Posterior reversible encephalopathy syndrome (PRES) is an uncommon but potentially devastating syndrome if not recognized and treated appropriately. As the name implies, recognition of the condition and proper management may reverse the clinical and radiological findings. However, diagnosis is not always straightforward. We present the case of a 24-year-old female who was 4 days post-partum and presented with headache, neck pain, and new-onset seizures. She had undergone epidural anesthesia during labor, and initial imaging was suggestive of intracranial hypotension versus pachymeningitis. Despite initial conservative therapy including anti-epileptic drugs, magnesium therapy, empiric antibiotics, and Trendelenburg positioning, the patient continued to deteriorate. Follow-up imaging was suggestive of PRES with signs of intracranial hypertension. The patient underwent a decompressive suboccipital craniectomy for refractory and severe PRES and later fully recovered. This case highlights the sometimes difficult diagnosis of PRES, possible association with pregnancy, eclampsia/preeclampsia and/or cerebrospinal fluid drainage, and the rare but life-saving need for decompression in severe cases.

Supplements, nutrition, and alternative therapies for the treatment of traumatic brain injury.

Studies using traditional treatment strategies for mild traumatic brain injury (TBI) have produced limited clinical success. Interest in treatment for mild TBI is at an all time high due to its association with the development of chronic traumatic encephalopathy and other neurodegenerative diseases, yet therapeutic options remain limited. Traditional pharmaceutical interventions have failed to transition to the clinic for the treatment of mild TBI. As such, many pre-clinical studies are now implementing non-pharmaceutical therapies for TBI. These studies have demonstrated promise, particularly those that modulate secondary injury cascades activated after injury. Because no TBI therapy has been discovered for mild injury, researchers now look to pharmaceutical supplementation in an attempt to foster success in human clinical trials. Non-traditional therapies, such as acupuncture and even music therapy are being considered to combat the neuropsychiatric symptoms of TBI. In this review, we highlight alternative approaches that have been studied in clinical and pre-clinical studies of TBI, and other related forms of neural injury. The purpose of this review is to stimulate further investigation into novel and innovative approaches that can be used to treat the mechanisms and symptoms of mild TBI.

Elucidating the role of compression waves and impact duration for generating mild traumatic brain injury in rats.

BACKGROUND: In total, 3.8 million concussions occur each year in the US leading to acute functional deficits, but the underlying histopathologic changes that occur are relatively unknown. In order to improve understanding of acute injury mechanisms, appropriately designed pre-clinical models must be utilized. METHODS: The clinical relevance of compression wave injury models revolves around the ability to produce consistent histopathologic deficits. Mild traumatic brain injuries activate similar neuroinflammatory cascades, cell death markers and increases in amyloid precursor protein in both humans and rodents. Humans, however, infrequently succumb to mild traumatic brain injuries and, therefore, the intensity and magnitude of impacts must be inferred. Understanding compression wave properties and mechanical loading could help link the histopathologic deficits seen in rodents to what might be happening in human brains following concussions. RESULTS: While the concept of linking duration and intensity of impact to subsequent histopathologic deficits makes sense, numerical modelling of compression waves has not been performed in this context. In this interdisciplinary work, numerical simulations were performed to study the creation of compression waves in an experimental model. CONCLUSION: This work was conducted in conjunction with a repetitive compression wave injury paradigm in rats in order to better understand how the wave generation correlates with histopathologic deficits.

Aneurysmal Subarachnoid Hemorrhage and Neuroinflammation: A Comprehensive Review.

Aneurysmal subarachnoid hemorrhage (SAH) can lead to devastating outcomes including vasospasm, cognitive decline, and even death. Currently, treatment options are limited for this potentially life threatening injury. Recent evidence suggests that neuroinflammation plays a critical role in injury expansion and brain damage. Red blood cell breakdown products can lead to the release of inflammatory cytokines that trigger vasospasm and tissue injury. Preclinical models have been used successfully to improve understanding about neuroinflammation following aneurysmal rupture. The focus of this review is to provide an overview of how neuroinflammation relates to secondary outcomes such as vasospasm after aneurysmal rupture and to critically discuss pharmaceutical agents that warrant further investigation for the treatment of subarachnoid hemorrhage. We provide a concise overview of the neuroinflammatory pathways that are upregulated following aneurysmal rupture and how these pathways correlate to long-term outcomes. Treatment of aneurysm rupture is limited and few pharmaceutical drugs are available. Through improved understanding of biochemical mechanisms of injury, novel treatment solutions are being developed that target neuroinflammation. In the final sections of this review, we highlight a few of these novel treatment approaches and emphasize why targeting neuroinflammation following aneurysmal subarachnoid hemorrhage may improve patient care. We encourage ongoing research into the pathophysiology of aneurysmal subarachnoid hemorrhage, especially in regards to neuroinflammatory cascades and the translation to randomized clinical trials.

Ischemic stroke injury is mediated by aberrant Cdk5.

Ischemic stroke is one of the leading causes of morbidity and mortality. Treatment options are limited and only a minority of patients receive acute interventions. Understanding the mechanisms that mediate neuronal injury and death may identify targets for neuroprotective treatments. Here we show that the aberrant activity of the protein kinase Cdk5 is a principal cause of neuronal death in rodents during stroke. Ischemia induced either by embolic middle cerebral artery occlusion (MCAO) in vivo or by oxygen and glucose deprivation in brain slices caused calpain-dependent conversion of the Cdk5-activating cofactor p35 to p25. Inhibition of aberrant Cdk5 during ischemia protected dopamine neurotransmission, maintained field potentials, and blocked excitotoxicity. Furthermore, pharmacological inhibition or conditional knock-out (CKO) of Cdk5 prevented neuronal death in response to ischemia. Moreover, Cdk5 CKO dramatically reduced infarctions following MCAO. Thus, targeting aberrant Cdk5 activity may serve as an effective treatment for stroke.

Medical student education in neurosurgery: optional or essential?

ISSUE: Current medical school curricula emphasize general practice principles, and this has led predictably to increasingly limited exposure to subspecialties, including neurosurgery. However, a significant amount of neurosurgical disease and/or emergencies present in primary care settings or emergency rooms. In light of an already acknowledged shortage of neurosurgery providers, this means that general practitioners should be well educated and prepared to diagnose and manage neurosurgical disease. Considering the devastating consequences of a missed or delayed neurosurgical diagnosis, limiting future physicians' exposure to the field of neurosurgery is not in the best interests of the patient. EVIDENCE: In this article, the authors review and discuss the results of several studies investigating the prevalence, presentation, diagnosis, and management of neurosurgical disease in emergency and general practice settings. They then discuss the current status of neurosurgical education in medical schools, both from the educators' and students' perspectives, and how this status might impact patient care. Finally, they offer suggestions for the improvement of neurosurgical education during medical school. IMPLICATIONS: Despite being considered highly subspecialized, neurosurgical diagnosis and care is a field in which all physicians should receive proper education and training. To properly serve patients and produce competent physicians, steps should be taken to re-emphasize the importance of neurosurgical education for medical students.

Intraoperative neuronavigation for transoral surgical approach: use of frameless stereotaxy with 3D rotational C-arm for image acquisition.

The transoral route is a standard surgical approach to the anterior craniovertebral junction, where neuronavigation is difficult secondary to the mobility of the cervical spine in relation to the cranium. We describe the use of neuronavigation combined with intraoperative 3D C-arm to direct our approach and resection of two lesions of the craniovertebral junction. Neuronavigation was employed in planning of incision, bony resection, and assessment of lesion resection. Both patients underwent transoral approach without complication using this method. Frameless stereotaxy with BrainLab VectorVision and 3D C-arm is an effective method of neuronavigated approach to the anterior craniocervical junction, which may contribute to the safety of this approach.

Transcranial orbital decompression for progressive compressive optic neuropathy after 3-wall decompression in severe graves' orbitopathy.

PURPOSE: To determine surgical outcomes after transcranial decompression of the superior orbit in patients with progressive compressive optic neuropathy (CON) secondary to Graves' orbitopathy (GO) who had previously been treated with 3-wall decompression. METHODS: Approval from the West Virginia University Institution Review Board was obtained. A retrospective review of 4 patients with GO who received bilateral transcranial decompression of the orbits for progressive compressive optic neuropathy after bilateral maximal extracranial 3-wall decompression was performed. The patients were treated by the Multidisciplinary Orbit and Skull Base Services at West Virginia University and the University of Michigan. RESULTS: Bilateral transcranial decompression of the orbit for GO was performed on 8 orbits in 4 patients. All 8 orbits had radiographic evidence of compression of the orbital apex, and all patients had been treated with steroids, orbital radiation, and bilateral 3-wall decompression. Preoperative vision ranged from 20/25 to 20/100, which improved to 20/25 or better in all eyes. The visual field mean deviation improved from a mean of -13.05 to -1.67 dB. Hertel measurements improved from a mean of 19.25 to 15.25 mm. Extraocular motility was essentially unchanged. Two patients were noted to have asymptomatic ocular pulsations. There were no other complications, and all patients remained stable during a follow-up period of 5 years (range 2-8 years). CONCLUSIONS: Transcranial decompression is an effective and safe method of salvaging vision when standard treatments fail. This is only the second report of transcranial decompression for refractory compressive optic neuropathy after decompression from a standard approach.

Bryostatin improves survival and reduces ischemic brain injury in aged rats after acute ischemic stroke.

BACKGROUND AND PURPOSE: Bryostatin, a potent protein kinase C (PKC) activator, has demonstrated therapeutic efficacy in preclinical models of associative memory, Alzheimer disease, global ischemia, and traumatic brain injury. In this study, we tested the hypothesis that administration of bryostatin provides a therapeutic benefit in reducing brain injury and improving stroke outcome using a clinically relevant model of cerebral ischemia with tissue plasminogen activator reperfusion in aged rats. METHODS: Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18- to 20-month-old female Sprague-Dawley rats using an autologous blood clot with tissue plasminogen activator-mediated reperfusion. Bryostatin was administered at 6 hours post-MCAO, then at 3, 6, 9, 12, 15, and 18 days after MCAO. Functional assessment was conducted at 2, 7, 14, and 21 days after MCAO. Lesion volume and hemispheric swelling/atrophy were performed at 2, 7, and 21 days post-MCAO. Histological assessment of PKC isozymes was performed at 24 hours post-MCAO. RESULTS: Bryostatin-treated rats showed improved survival post-MCAO, especially during the first 4 days. Repeated administration of bryostatin post-MCAO resulted in reduced infarct volume, hemispheric swelling/atrophy, and improved neurological function at 21 days post-MCAO. Changes in αPKC expression and εPKC expression in neurons were noted in bryostatin-treated rats at 24 hours post-MCAO. CONCLUSIONS: Repeated bryostatin administration post-MCAO protected the brain from severe neurological injury post-MCAO. Bryostatin treatment improved survival rate, reduced lesion volume, salvaged tissue in infarcted hemisphere by reducing necrosis and peri-infarct astrogliosis, and improved functional outcome after MCAO.

Neuroprotection for ischemic stroke: moving past shortcomings and identifying promising directions.

The translation of neuroprotective agents for ischemic stroke from bench-to-bedside has largely failed to produce improved treatments since the development of tissue plasminogen activator (tPA). One possible reason for lack of translation is the failure to acknowledge the greatest risk factor for stroke, age, and other common comorbidities such as hypertension, obesity, and diabetes that are associated with stroke. In this review, we highlight both mechanisms of studying these factors and results of those that have been addressed. We also discuss the potential role of other lifestyle factors associated with an increased stroke risk such as sleep fragmentation and/or deprivation. Furthermore, many proposed therapeutic agents have targeted molecular mechanisms occurring soon after the onset of ischemia despite data indicating delayed patient presentation following ischemic stroke. Modulating inflammation has been identified as a promising therapeutic avenue consistent with preliminary success of ongoing clinical trials for anti-inflammatory compounds such as minocycline. We review the role of inflammation in stroke and in particular, the role of inflammatory cell recruitment and macrophage phenotype in the inflammatory process. Emerging evidence indicates an increasing role of neuro-immune crosstalk, which has led to increased interest in identification of peripheral biomarkers indicative of neural injury. It is our hope that identification and investigation of factors influencing stroke pathophysiology may lead to improved therapeutics.

Potential age-dependent effects of estrogen on neural injury.

In 2000, approximately 10 million women were receiving hormone replacement therapy (HRT) for alleviation of menopausal symptoms. A number of prior animal studies suggested that HRT may be neuroprotective and cardioprotective. Then, in 2003, reports from the Women's Health Initiative (WHI) indicated that long-term estrogen/progestin supplementation led to increased incidence of stroke. A second branch of the WHI in women with prior hysterectomy found an even stronger correlation between estrogen supplementation alone and stroke incidence. Follow-up analyses of the data, as well as data from other smaller clinical trials, have also demonstrated increased stroke severity in women receiving HRT or estrogen alone. This review examines the studies indicating that estrogen is neuroprotectant in animal models and explores potential reasons why this may not be true in postmenopausal women. Specifically, age-related differences in estrogen receptors and estrogenic actions in the brain are discussed, with the conclusion that animal models of disease must closely mimic human disease to produce clinically relevant results.

Age and the metabolic syndrome as risk factors for ischemic stroke: improving preclinical models of ischemic stroke.

Ischemic stroke represents a leading cause of morbidity and mortality in the developed world. This disabling and sometimes fatal event puts an ever increasing burden on the family members and medical professionals who care for stroke victims. Preclinical ischemic stroke research has predominantly utilized young adult, healthy animals, a clear discrepancy when considering the clinical population affected by stroke. A broad spectrum of risk factors such as age, obesity, diabetes, and hypertension has been associated with an increased stroke risk. The effect of these comorbidities on both stroke pathophysiology and outcome has not been emphasized and has been recognized as a shortcoming of preclinical studies. By addressing these conditions in experimental models of ischemic stroke, it may be possible to more accurately represent the clinical scenario and improve therapeutic translation from bench-to-bedside. In this work, we review many of the risk factors associated with increased stroke risk, particularly as each risk factor relates to inflammation. Additionally, we explore potential animal models that could be utilized in identifying the contribution of these risk factors to stroke outcome. By investigating the risk factors for stroke and how these may alter stroke pathophysiology, the present discrepancies between preclinical studies and the clinical reality can be reconciled in an effort to improve therapeutic development and translation from bench-to-bedside.

A survey study of occupational pain and injury in ophthalmic plastic surgeons.

PURPOSE: To determine factors associated with pain/injury related to practicing ophthalmic plastic and reconstructive surgery. METHODS: A 29-question electronic survey was sent to the American Society of Ophthalmic Plastic and Reconstructive Surgery's listserv. The Chi-Squared Automatic Interaction Detector technique was used to generate a decision tree using SPSS software. The levels of dendograms were limited to 8. Significance was pre-established at α = 0.05. RESULTS: One hundred thirty surveys were completed, and 72.5% reported pain associated with operating, 80.9% reported use of loupe magnification, 68.7% reported use of a headlight, 42.5% reported modification of their operating room practice, and 9.2% reported stopping operating due to pain or spine injury. Most respondents regularly exercise, with 55.7% characterizing the amount of exercise as less than necessary; 60.8% and 57.3% agreed that loupe use and headlamp use, respectively, can lead to spine problems.Chi-Squared Automatic Interaction Detector analysis found that 62.7% (n = 47) with neck pain had modified their operating room practice, compared with 13.5% (n = 7) without pain (χ = 30.42; df = 1; p < 0.001); All surgeons that had to stop operating (n = 9) had tried modifying their operating room practice; over half (57.6%, n = 38) of practicing surgeons had changed their operating room practice (χ = 6.09; df = 1; p = 0.014). The majority who exercised 5 hours or less had modified their operating room practice (70.2%, n = 33), compared with 26.3% (n = 5) who exercised more. CONCLUSIONS: Many oculoplastic surgeons experience discomfort due to operating, and an alarming minority have stopped operating due to pain or neck injury. Participants identified loupe and headlamp use as a special concern.

Medical management of cerebellar abscess: a case report and review of the literature.

A large abscess of the posterior fossa often warrants surgical intervention. We report a case of a 50-year-old male presenting with a cerebellar abscess measuring 2.8 cm x 1.6 cm located in the left cerebellar hemisphere at the level of the middle cerebellar peduncle that was treated conservatively and successfully with antibiotics. Therapeutic management options are discussed in regards to this case specifically as well as a review of the literature. This case illustrates the successful medical management of a cerebellar abscess of otogenic origin in an adult, a unique result in terms of abscess size and age of the patient.

Low-intensity Blast Wave Model for Preclinical Assessment of Closed-head Mild Traumatic Brain Injury in Rodents.

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of medical visits in the United States. There are currently no FDA-approved treatments available for TBI. The increased incidence of military-related, blast-induced TBI further accentuates the urgent need for effective TBI treatments. Therefore, new preclinical TBI animal models that recapitulate aspects of human blast-related TBI will greatly advance the research efforts into the neurobiological and pathophysiological processes underlying mild to moderate TBI as well as the development of novel therapeutic strategies for TBI. Here we present a reliable, reproducible model for the investigation of the molecular, cellular, and behavioral effects of mild to moderate blast-induced TBI. We describe a step-by-step protocol for closed-head, blast-induced mild TBI in rodents using a bench-top setup consisting of a gas-driven shock tube equipped with piezoelectric pressure sensors to ensure consistent test conditions. The benefits of the setup that we have established are its relative low-cost, ease of installation, ease of use and high-throughput capacity. Further advantages of this non-invasive TBI model include the scalability of the blast peak overpressure and the generation of controlled reproducible outcomes. The reproducibility and relevance of this TBI model has been evaluated in a number of downstream applications, including neurobiological, neuropathological, neurophysiological and behavioral analyses, supporting the use of this model for the characterization of processes underlying the etiology of mild to moderate TBI.

The use of MR-myelography combining flexion and extension imaging in the diagnosis of cervical myelopathy: a case report.

This report describes the use of a non-invasive MR-Myelogram combining flexion and extension views to demonstrate causative factors in cervical myelopathy. Utilizing a new approach to MRI, mimicking an older technique of flexion/extension cervical myelography, we were able to identify the pathology of a patient suffering from progressive cervical myelopathy. We report a patient suffering from progressive multilevel cervical myelopathy due to posterior compression of the spinal cord by an inbuckling ligamentum flavum. Neutral position radiologic assessment failed to reveal any significant spinal cord compression. In this patient, the dynamic MRI and MR-Myelography was critical for demonstrating the posterior compression of the spinal cord by the ligamentum flavum. Flexion and extension MRI images of the cervical spine complemented by non-invasive MR-myelography were obtained. Surgical decompression was indicated based on these additional studies. The use of invasive myelography and in particular, flexion/extension myelography is in decline. MR-myelography combining flexion and extension views can be a useful noninvasive means of studying patients with possible ligamentous hypertrophy and dynamic cord compression.

Venous Manometry as an Adjunct for Diagnosis and Multimodal Management of Intracranial Hypertension due to Meningioma Compressing Sigmoid Sinus.

Intracranial venous hypertension is a rare presentation of meningiomas in the transverse-sigmoid sinus region. We describe a case of a young patient presenting with intracranial hypertension due to a meningioma causing compression of the dominant sigmoid sinus. We were able to document the cerebral venous pressure gradient across the lesion confirming our hypothesis that compression of the sigmoid sinus from the meningioma was the cause of intracranial hypertension. The patient is a 17-year-old male who presented with intracranial hypertension due to meningioma at the right dominant sigmoid sinus, which was treated by a Simpson grade IV surgical resection followed by stereotactic radiosurgery. Following treatment, his papilledema resolved and he remains symptom-free at 18 months. In conclusion, venous manometry is a useful adjunct to diagnose intracranial hypertension in non-idiopathic causes of intracranial hypertension. A multimodal management approach of intracranial hypertension due to outflow obstruction from the dominant sinus led to an excellent recovery on follow up.

Single-stage complex reconstruction for fibrous dysplasia: a case report.

OBJECTIVE AND IMPORTANCE: Fibrous dysplasia is a benign skeletal condition which can involve the craniofacial skeleton. Surgery is indicated for correction of deformity and neurovascular decompression. Traditional surgery involves harvesting remote bone or calvarial grafts, requiring prolonged, multisite procedures. Custom implants may eliminate the need for bone harvesting, but usually require staged procedures with interim bony defects. We report the use of preoperative cranial modeling and implant design, allowing for a single reconstructive procedure. CLINICAL PRESENTATION: A 32-year-old woman with McCune-Albright syndrome was referred to Neurosurgery and Ophthalmology for right facial pain, deformity, and eye pressure. Examination revealed a 6-mm right eye proptosis and decreased sensation and severe pain in the right V2 distribution. Imaging demonstrated extensive fibrous dysplasia, with right orbital mass effect and nerve compression. INTERVENTION: A single procedure was planned to remove and replace the involved bone. High-resolution CT was used to create a scale model of the patient's cranium. The planned resection was performed on the model, allowing for preoperative custom implant design. We then performed single-stage resection and reconstruction. The right superior and lateral orbital rims, portions of the left superior and medial orbital rims, and the nasion were resected. The custom implant was contoured to fit and remaining small defects were filled with Fast Set Norian. No complications occurred. At follow-up, the patient reported pain and pressure relief, and examination showed resolution of proptosis, improved sensation, and excellent cosmesis. CONCLUSION: Preoperative cranial modeling and implant design allows for a shorter, one-step resection and reconstruction procedure without compromising structural or cosmetic outcome.

Chordoma of the anterior cranial fossa and ethmoids with orbital involvement.

PURPOSE: To report a case of orbital chordoma, emphasizing the clinical, operative, and histopathologic findings, and to review similar English-language reports. METHODS: This is a single case report with histopathologic correlation. Search of the English-language literature and review of referenced citations was performed. RESULTS: After treatment with resection and proton beam radiation, our patient is alive, without recurrence at 3-year follow-up. Biopsy of the recurrent tumor was consistent with chordoma. The original biopsy had S100 and pancytokeratin-positive tumor cells, with abundant clear to eosinophilic cytoplasm. Focal EMA positivity was present. Literature review identified 14 additional cases. CONCLUSION: Orbital chordoma is rare. Extraocular motility disturbances occur solely with intracranial lesions as well as those extending into the orbit, but globe displacement is the most common sign of orbital involvement. This tumor often recurs in the path of previous resection. Diagnosis is confirmed by distinctive histopathologic features and positive staining for S100, pancytokeratin, and EMA. Treatment and outcome analysis of orbital chordoma is difficult due to its rarity and lack of reported follow-up and may need to be extrapolated from reported skull base cases.

The potential dangers of neck manipulation & risk for dissection and devastating stroke: An illustrative case & review of the literature.

Chiropractic cervical manipulation is a common practice utilized around the world. Most patients are never cleared medically for manipulation, which can be devastating for those few who are at increased risk for dissections. The high velocity thrust used in cervical manipulation can produce significant strain on carotid and vertebral vessels. Once a dissection has occurred, the risk of thrombus formation, ischemic stroke, paralysis, and even death is drastically increased. In this case report, we highlight a case of a 32-year-old woman who underwent chiropractic manipulation and had vertebral artery dissection with subsequent brainstem infarct. She quickly deteriorated and passed away shortly after arrival to the hospital. Although rare, one in 48 chiropractors have experienced such an event. We utilize this case to highlight the risk associated with cervical manipulation and urge open dialogue between chiropractors and physicians. Receiving medical clearance prior to cervical manipulation in potential at risk patients would drastically reduce morbidity and mortality.