Unusual presentation of glioblastoma in the brainstem: a case report of a diffuse pontine glioblastoma multiforme and surgical management.

Diffuse pontine glioblastoma multiforme is a rare subtype of glioblastoma associated with a poor prognosis. In this case report, we present a unique case of diffuse primary pontine glioblastoma multiforme in a patient without any supratentorial lesions. We review the symptoms, treatment options, and case management of patients with infratentorial glioblastoma multiforme and compare these with our patient. Our patient presented with symptoms including progressive diplopia, gait disturbance, and lower extremity weakness. Magnetic resonance imaging revealed a diffuse lesion involving the pons and biopsy revealed only mildly-atypical glial infiltrates. Consequentially, diagnosis was driven by genetic analysis. Due to the location of the tumor, surgery was not considered a viable option. Instead, the patient received radiation therapy along with concomitant and adjuvant temozolomide chemotherapy which has resulted in improvement of symptoms. This case highlights the challenges of managing diffuse primary pontine glioblastoma multiforme and the need for more effective treatment options for this rare subtype of glioblastoma. Despite aggressive treatment, the prognosis for patients with infratentorial glioblastoma multiforme remains poor, with a median survival time of less than a year. Further research is needed to improve our understanding of the biology and optimal management of this disease.

Giant primary intracranial multi-fossa leiomyosarcoma involving the frontal sinus, ethmoid air cells, anterior fossa, middle fossa, and intraventricular space: A case report and literature review.

Background: Leiomyosarcomas (LMSs) is a type of sarcoma that arises from smooth muscle and generally presents in the abdomen. Although intracranial LMS has been identified before, most reported presentations have been in immunocompromised patients. Here, we present an intracranial LMS in an immunocompetent patient. Case Description: A 22-year-old male with a history of an atypical pineal parenchymal tumor of intermediate differentiation resected by suboccipital craniotomy at the age of 12 followed by adjuvant radiation therapy, presented with 3 weeks of decreased appetite, weight loss, and lethargy. He subsequently underwent transbasal approach skull base tumor resection. Histologic examination of the mass along with the patient's history of radiation was supportive of a low-grade, radiation-induced LMS arising from the anterior fossa of the skull or meninges and extends to the frontal sinus and ethmoid air cells. Conclusion: Primary intracranial LMS is an extremely rare diagnosis and presenting symptoms vary with the location and size of the tumor. Due to the poor specificity of clinical symptoms, diagnosis is often based on histology. The most common treatment is surgical resection. Adjuvant chemotherapy with various agents has been found to be somewhat effective outside the central nervous system. When LMS does occur, a history of immunocompromised state or previous radiation exposure is often present. Pathological confirmation is required for an appropriate diagnosis.

Radiation Myelopathy: A Case Report and Literature Review.

Proton beam therapy is a common type of radiation treatment that delivers a beam of proton particles to treat cancer and minimize damage to nearby healthy tissue. In this paper, we describe a case of a 20-year-old male patient with osteosarcoma of the distal right femur that eventually metastasized to his thoracic cavity. The patient underwent radiation beam therapy treatment that was directed at his left thorax and nine months later presented with clinical and radiographic findings of delayed radiation myelopathy (RM).

Pediatric abusive head trauma: ThinkFirst national injury prevention foundation.

BACKGROUND: Pediatric abusive head trauma (AHT) represents 80% of nonaccidental trauma deaths, remaining a lead cause of death among infants and young children. Furthermore, neurosurgical intervention can ameliorate damage from secondary injury, but we are currently unable to alter the impact of the primary injury. Thus, prevention through increased public awareness is imperative. This study identifies injuries and predictors of outcomes in pediatric AHT and highlights the importance of partnering with our community through ThinkFirst, a national injury prevention foundation, to educate parents and caregivers about prevention. METHODS: This single-institution retrospective review identifies injuries and predictors of outcomes in pediatric AHT and highlights the importance of partnering with our community to raise awareness and educate parents and caregivers about prevention. RESULTS: The number of pediatric AHT cases continues to steadily increase over time (P < 0.001), and over 70% of these patients are <1 year of age (P < 0.001). Patients suffering AHT have a mortality rate of nearly 10%. In addition to morbidity and mortality, the economic burden of caring for abused children is high as they often require high levels of care, long hospital stays, and extensive rehabilitation. Furthermore, Medicaid pays for nearly 80% of these patients. CONCLUSION: The population of patients with AHT is unique, and one that will benefit from continued efforts at increased multidisciplinary and public awareness. Prevention of AHT through awareness is critical. Through partnering with ThinkFirst, a national injury prevention foundation, we aim to educate parents and caregivers about prevention.

Spinal Cord Stimulator Paddle Lead Surgery Complicated by Cerebrospinal Fluid Leak and Fistula Formation.

Spinal cord stimulation (SCS) paddle leads placed via laminectomy procedures have become common as more data accumulates with regards to their clinical efficacy. In this paper, we describe a case of a 72-year-old male patient with failed back surgery syndrome (FBSS) who underwent a thoracic laminectomy for permanent paddle lead placement. He went on to develop a complication that resulted in a large cerebrospinal fluid leak with a cerebrospinal fluid fistula formation.

Retractorless interhemispheric transtentorial approach for large lesions in the posterior incisural space.

BACKGROUND: Surgical resection of lesions in the posterior incisural space presents a significant surgical challenge, which may result in postoperative visual complications and other neurological deficits. We, therefore, describe a retractorless interhemispheric transtentorial approach that avoids surrounding brain structures with positive outcomes and no complications or visual damage. CASE DESCRIPTION: We present four cases of lesions in the posterior incisural space that was treated with a retractorless interhemispheric transtentorial approach. Two patients were previously seen at another institution for a falcotentorial meningioma. We resected the meningiomas with a parietal-occipital interhemispheric transtentorial approach with no neurological deficits. A third patient presented with a large superior vermian hemangioblastoma with a steep angle of the tentorium. The fourth patient had a large upper vermian metastatic lesion with progressive enlargement, which was refractory to radiation treatments and chemotherapy, and we achieved partial resection. Postoperative visual function was completely preserved in all patients. CONCLUSION: A carefully executed retractorless interhemispheric approach in select cases is an effective option to reduce morbidity and prevent visual complications when removing lesions in the posterior tentorial incisure.

Benign Giant Cell Lesion of C1 Lateral Mass: A Case Report and Literature Review.

Primary osseous tumors of the spinal column account for approximately 1% of the total number of spinal tumors found in the pediatric patient population. The authors present a case of a C1 benign giant cell lesion that was incidentally found in a 15-year-old patient. A transoral biopsy was performed followed by treatment with denosumab, with definitive management in the form of transoral tumor resection with subsequent occiput-cervical three posterior instrumented fusion. The patient tolerated all of the procedures well, as there were no post-operative complications, discharged home neurologically intact and was eager to return to school when assessed during a follow-up visit in clinic. Osteolytic lesions affecting the cervical spine are rare in the pediatric population. It is of utmost importance to have sufficient background knowledge in order to formulate a differential diagnosis, as well as an understanding of principles underlying surgical techniques required to prevent occipital-cervical instability in this patient population. The information presented will guide surgical decision-making by identifying the patient population that would benefit from neurosurgical interventions to stabilize the atlantoaxial junction, in the context of rare osteolytic conditions affecting the cervical spine.

Preparation of Rhythmically-active In Vitro Neonatal Rodent Brainstem-spinal Cord and Thin Slice.

Mammalian inspiratory rhythm is generated from a neuronal network in a region of the medulla called the preBötzinger complex (pBC), which produces a signal driving the rhythmic contraction of inspiratory muscles. Rhythmic neural activity generated in the pBC and carried to other neuronal pools to drive the musculature of breathing may be studied using various approaches, including en bloc nerve recordings and transverse slice recordings. However, previously published methods have not extensively described the brainstem-spinal cord dissection process in a transparent and reproducible manner for future studies. Here, we present a comprehensive overview of a method used to reproducibly cut rhythmically-active brainstem slices containing the necessary and sufficient neuronal circuitry for generating and transmitting inspiratory drive. This work builds upon previous brainstem-spinal cord electrophysiology protocols to enhance the likelihood of reliably obtaining viable and rhythmically-active slices for recording neuronal output from the pBC, hypoglossal premotor neurons (XII pMN), and hypoglossal motor neurons (XII MN). The work presented expands upon previous published methods by providing detailed, step-by-step illustrations of the dissection, from whole rat pup, to in vitro slice containing the XII rootlets.

Microsurgical Technique for Basilar Apex Aneurysm Clipping: Two-Dimensional Video.

We present the case of a 57-year-old female with hypertension, current smoker status, and recent headaches. Imaging studies showed an unruptured 8-mm basilar apex wide neck aneurysm located 4 mm above posterior clinoid (Figure 1) with a 3-mm anterior communicant artery aneurysm. No contraindications were encountered for endovascular treatment, although after we evaluated endovascular and surgical options, surgical clipping was considered also a safe and favorable option based on anterior projection of aneurysm, height of the basilar artery bifurcation, small and elongated posterior communicant artery, and available space between posterior clinoid and basilar artery (4 mm). The presence of a second aneurysm increased the patient's interest in a more definitive treatment, as we mentioned the possibility of its treatment if considered safe intraoperatively. A cranio-orbito-zygomatic craniotomy, anterior clinoidectomy, and sylvian fissure dissection was performed with electrophysiology monitoring. The exposure was enhanced by sphenoparietal sinus ligation, and the anterior clinoidectomy allowed working spaces at optic-carotid and carotid-oculomotor spaces for Liliequist membrane dissection, without need for posterior clinoid removal (Figure 2). Brief temporary clipping at basilar trunk below superior cerebellar arteries at perforating free zone was performed. Two clips were applied, obliterating adequately the aneurysm respecting perforating vessels. After the basilar apex aneurysm clipping, we proceeded in a standard fashion to clip the additional anterior communicant artery aneurysm. Micro-Doppler and intraoperative angiogram confirmed aneurysm exclusion and patent parent vessels (Video 1). The patient developed minimal ptosis due to partial right oculomotor nerve palsy that recovered completely in 2 weeks; otherwise, her neurologic exam was normal. At 1-year follow up, computed tomography angiography showed complete aneurysm exclusion.

Mitophagy Reduces Oxidative Stress Via Keap1 (Kelch-Like Epichlorohydrin-Associated Protein 1)/Nrf2 (Nuclear Factor-E2-Related Factor 2)/PHB2 (Prohibitin 2) Pathway After Subarachnoid Hemorrhage in Rats.

Background and Purpose- Mitoquinone has been reported as a mitochondria-targeting antioxidant to promote mitophagy in various chronic diseases. Here, our aim was to study the role of mitoquinone in mitophagy activation and oxidative stress-induced neuronal death reduction after subarachnoid hemorrhage (SAH) in rats. Methods- Endovascular perforation was used for SAH model of male Sprague-Dawley rats. Exogenous mitoquinone was injected intraperitoneally 1 hour after SAH. ML385, an inhibitor of Nrf2 (nuclear factor-E2-related factor 2), was given intracerebroventricularly 24 hours before SAH. Small interfering RNA for PHB2 (prohibitin 2) was injected intracerebroventricularly 48 hours before SAH. Nuclear, mitochondrial, and cytoplasmic fractions were gathered using nucleus and mitochondria isolation kits. SAH grade evaluation, short- and long- term neurological function tests, oxidative stress, and apoptosis measurements were performed. Pathway related proteins were investigated with Western blot and immunofluorescence staining. Results- Expression of Keap1 (Kelch-like epichlorohydrin-associated protein 1, 2.84× at 24 hours), Nrf2 (2.78× at 3 hours), and LC3II (light chain 3-II; 1.94× at 24 hours) increased, whereas PHB2 (0.46× at 24 hours) decreased after SAH compared with sham group. Mitoquinone treatment attenuated oxidative stress and neuronal death, both short-term and long-term. Administration of mitoquinone resulted in a decrease in expression of Keap1 (0.33×), Romo1 (reactive oxygen species modulator 1; 0.24×), Bax (B-cell lymphoma-2 associated X protein; 0.31×), Cleaved Caspase-3 (0.29×) and an increase in Nrf2 (2.13×), Bcl-xl (B-cell lymphoma-extra large; 1.67×), PINK1 (phosphatase and tensin-induced kinase 1; 1.67×), Parkin (1.49×), PHB2 (1.60×), and LC3II (1.67×) proteins compared with SAH+vehicle group. ML385 abolished the treatment effects of mitoquinone on behavior and protein levels. PHB2 small interfering RNA reversed the outcomes of mitoquinone administration through reduction in protein expressions downstream of PHB2. Conclusions- Mitoquinone inhibited oxidative stress-related neuronal death by activating mitophagy via Keap1/Nrf2/PHB2 pathway after SAH. Mitoquinone may serve as a potential treatment to relieve brain injury after SAH.

Houdini Tumor: Case Report and Literature Review of Pregnancy-Associated Meningioma.

BACKGROUND: Meningiomas are common intracranial neoplasms of undetermined etiology. Accelerated growth during episodes of elevated serum estrogen and progesterone have been demonstrated in pregnant patients, as exhibited by an overexpression of estrogen or progesterone on immunohistochemical analysis. This case report and literature review describe a case of complete meningioma regression in a postpartum patient. CASE DESCRIPTION: A 23-year-old female presented at 37 weeks of pregnancy with 1-month history of fluctuating severe left-sided headaches, periodic blurry vision, nausea, and vomiting. She had 2 previous pregnancies without complication. Magnetic resonance imaging revealed a dural-based, heterogeneously enhancing mass along the left tentorium, just posterior to the transverse sinus, with supratentorial extension and surrounding edema. Differential diagnoses included meningioma versus hemangioma versus hemangiopericytoma. The patient followed up with neurosurgery 1 month after delivery. She had continued left-sided headaches but no longer complained of visual changes. A postpartum surgical resection via left occipital and suboccipital craniotomy was planned. Approximately 1 month later (now about 3 months after delivery) a repeat magnetic resonance imaging demonstrated a marked decrease in meningioma size, and the previously seen edema had resolved. In light of the sudden disappearance of the meningioma, no further surgical intervention was pursued. CONCLUSIONS: Because meningioma shrinkage or disappearance may occur after pregnancy, repeat imaging is advised as part of a preoperative evaluation. In addition, it is possible that an undetermined amount of meningioma removal surgeries may be avoided with further research into monitoring hormone levels connected to meningioma growth.

Computed Tomography Cisternography for Evaluation of Trigeminal Neuralgia When Magnetic Resonance Imaging Is Contraindicated: Case Report and Review of the Literature.

BACKGROUND: Trigeminal neuralgia (TGN) causes severe unilateral facial pain. The etiology is hypothesized to be segmental demyelination of the trigeminal nerve root via compression by the superior cerebellar artery (SCA). Microvascular decompression (MVD) allows immediate and long-term pain relief. Preoperative evaluation includes magnetic resonance imaging (MRI) and/or magnetic resonance angiography of the brain. Having a pacemaker is a contraindication for MRI. There have been isolated reports of using computed tomography (CT) cisternography scans for radiation planning for TGN. CASE DESCRIPTION: A 75-year-old male with a permanent pacemaker who had refractory TGN in the V2 (maxillary) distribution of the trigeminal nerve underwent CT cisternography to prepare for MVD. CT angiography with Isovue 370 intravenous contrast injection and 0.625-mm axial images were obtained from the skull base across the posterior fossa. An intrathecal injection of Isovue 180 was performed at the L2/3 level. Imaging revealed the right SCA abutting the medial margin of the proximal right trigeminal nerve. In surgery (K.D.), a standard retrosigmoid suboccipital craniotomy was performed to access the cerebellopontine angle and separate the abutting SCA and trigeminal nerve. The patient had immediate pain relief. CONCLUSIONS: MRI is the preferred method of evaluating for TGN because it offers excellent visualization of vasculature in relation to the trigeminal nerve without accompanying radiation exposure. However, for patients who have contraindications to MRI, CT cisternography is shown to also be an effective method for visualizing the trigeminal root entry zone and nearby vasculature in preparation for MVD of the trigeminal nerve.

Exendin-4 attenuates neuronal death via GLP-1R/PI3K/Akt pathway in early brain injury after subarachnoid hemorrhage in rats.

Neuronal apoptosis is considered to be a crucial therapeutic target against early brain injury (EBI) after subarachnoid hemorrhage (SAH). Emerging evidence indicates that Exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, plays a neuroprotective role in cerebrovascular disease. This study was conducted in order to verify the neuroprotective role of EX-4 in EBI after SAH in rats. The endovascular perforation model of SAH was performed in Sprague-Dawley rats (n = 153). Ex-4 was intraperitoneally injected 1 h after SAH induction in the rats (SAH + Ex-4). To elucidate the underlying molecular mechanism, small interfering ribonucleic acid (siRNA) for GLP-1R and a specific inhibitor of PI3K, LY294002, were injected intracerebroventricularly into SAH + Ex-4 rats before induction of SAH (n = 6 per group). SAH grading evaluation, immunohistochemistry, Western blots, neurobehavioral assessment, and Fluoro-Jade C (FJC) staining experiments were performed. Expression of GLP-1R was significantly increased and mainly expressed in neurons at 24 h after SAH induction. Administration of Ex-4 significantly improved both short- and long-term neurobehavior in SAH + Ex-4 group compared to SAH + Vehicle group after SAH. Ex-4 treatment significantly increased the expression of GLP-1R, PI3K, p-Akt, Bcl-xl, and Bcl-2, while at the same time was found to decrease expression of Bax in the brain. Effects of Ex-4 were reversed by the intervention of GLP-1R siRNA and LY294002 in SAH + Ex-4+GLP-1R siRNA and SAH + Ex-4+LY294002 groups, respectively. In conclusion, the neuroprotective effect of Ex-4 in EBI after SAH was mediated by attenuation of neuronal apoptosis via GLP-1R/PI3K/Akt signaling pathway, therefore EX-4 should be further investigated as a potential therapeutic agent in stroke patients.

A Look into Stem Cell Therapy: Exploring the Options for Treatment of Ischemic Stroke.

Neural stem cells (NSCs) offer a potential therapeutic benefit in the recovery from ischemic stroke. Understanding the role of endogenous neural stem and progenitor cells under normal physiological conditions aids in analyzing their effects after ischemic injury, including their impact on functional recovery and neurogenesis at the site of injury. Recent animal studies have utilized unique subsets of exogenous and endogenous stem cells as well as preconditioning with pharmacologic agents to better understand the best situation for stem cell proliferation, migration, and differentiation. These stem cell therapies provide a promising effect on stimulation of endogenous neurogenesis, neuroprotection, anti-inflammatory effects, and improved cell survival rates. Clinical trials performed using various stem cell types show promising results to their safety and effectiveness on reducing the effects of ischemic stroke in humans. Another important aspect of stem cell therapy discussed in this review is tracking endogenous and exogenous NSCs with magnetic resonance imaging. This review explores the pathophysiology of NSCs on ischemic stroke, stem cell therapy studies and their effects on neurogenesis, the most recent clinical trials, and techniques to track and monitor the progress of endogenous and exogenous stem cells.

Traumatic Brain Injury and Stem Cell: Pathophysiology and Update on Recent Treatment Modalities.

Traumatic brain injury (TBI) is a complex condition that presents with a wide spectrum of clinical symptoms caused by an initial insult to the brain through an external mechanical force to the skull. In the United States alone, TBI accounts for more than 50,000 deaths per year and is one of the leading causes of mortality among young adults in the developed world. Pathophysiology of TBI is complex and consists of acute and delayed injury. In the acute phase, brain tissue destroyed upon impact includes neurons, glia, and endothelial cells, the latter of which makes up the blood-brain barrier. In the delayed phase, "toxins" released from damaged cells set off cascades in neighboring cells eventually leading to exacerbation of primary injury. As researches further explore pathophysiology and molecular mechanisms underlying this debilitating condition, numerous potential therapeutic strategies, especially those involving stem cells, are emerging to improve recovery and possibly reverse damage. In addition to elucidating the most recent advances in the understanding of TBI pathophysiology, this review explores two primary pathways currently under investigation and are thought to yield the most viable therapeutic approach for treatment of TBI: manipulation of endogenous neural cell response and administration of exogenous stem cell therapy.

Pathophysiology and the Monitoring Methods for Cardiac Arrest Associated Brain Injury.

Cardiac arrest (CA) is a well-known cause of global brain ischemia. After CA and subsequent loss of consciousness, oxygen tension starts to decline and leads to a series of cellular changes that will lead to cellular death, if not reversed immediately, with brain edema as a result. The electroencephalographic activity starts to change as well. Although increased intracranial pressure (ICP) is not a direct result of cardiac arrest, it can still occur due to hypoxic-ischemic encephalopathy induced changes in brain tissue, and is a measure of brain edema after CA and ischemic brain injury. In this review, we will discuss the pathophysiology of brain edema after CA, some available techniques, and methods to monitor brain oxygen, electroencephalography (EEG), ICP (intracranial pressure), and microdialysis on its measurement of cerebral metabolism and its usefulness both in clinical practice and possible basic science research in development. With this review, we hope to gain knowledge of the more personalized information about patient status and specifics of their brain injury, and thus facilitating the physicians' decision making in terms of which treatments to pursue.

Rare Intradural Cervical Nerve Root Metastasis of Follicular Thyroid Carcinoma.

Intradural extramedullary nerve root metastasis is extremely unusual with only a handful of cases reported, and it presents most commonly in the thoracic and lumbosacral regions. We report the first case of metastasis to a ventral cervical nerve root in a patient with low-grade follicular thyroid carcinoma thought to be in remission for several years. Histopathology demonstrated malignant transformation and invasion of the nerve root. This case underscores that any history of malignancy regardless of staging, grading, or remission status should raise the suspicion of metastasis as it can mimic other spine and nerve sheath tumors and represent malignant transformation. Gross total resection can be safely achieved with intraoperative neuromonitoring and result in improved function; however, treatment is likely palliative.

Treatment of IgG4-related pachymeningitis in a patient with steroid intolerance: The role of early use of rituximab.

IgG4-related pachymeningitis is a serious inflammatory condition that can present with symptoms of mass effect and focal deficits. The first-line therapy is steroids and second-line is chemotherapy (methotrexate, azathioprine, etc.). We describe a patient with IgG4-related pachymeningitis in whom steroid use was contraindicated and methotrexate was ineffective. During the course of treatment, the patient presented to the emergency department with receptive and expressive aphasia, slurred speech, right-sided neglect, and loss of sensation. After a single infusion of rituximab and anticonvulsants, her symptoms resolved. Our unique case suggests that patients with IgG4-related pachymeningitis might benefit from early initiation of rituximab.

Increased cortical expression of FK506 binding protein-51 in HIV-associated neurocognitive disorders.

FK506 binding protein (FKBP)-51 and FKBP52 act as molecular chaperones to control glucocorticoid receptor (GR) sensitivity. Dysregulation of proteins involved in GR-mediated signaling can lead to maladaptive stress response and aging-related cognitive decline. As HIV infection is related to chronic stress, we hypothesized that altered cortical expression of these proteins was associated with HIV-associated neurocognitive disorders (HAND). We used quantitative immunohistochemistry to assess expression levels of these proteins in the mid-frontal gyrus of 55 HIV-infected subjects free of cerebral opportunistic diseases compared to 20 age-matched non-HIV controls. The immunoreactivity normalized to the neuroanatomic area measured (IRn) for FKBP51 was increased in HIV subjects both in the cortex and subcortical white matter (p < 0.0001, U test), while no significant alterations were observed for GR or FKBP52. Notably, the cortical FKBP51 IRn was higher in HAND subjects than in cognitively normal HIV subjects (p = 0.02, U test). There was also a trend for increasing cortical FKBP51 IRn with the increasing severity of HAND (p = 0.08, Kruskal-Wallis test). No significant changes in FKBP51 IRn were found with respect to hepatitis C virus infection, lifetime methamphetamine use, or antiretroviral treatment in HIV subjects. In conclusion, the increased cortical expression of FKBP51 (an inhibitor for GR activity) might represent negative feedback in an attempt to reduce GR sensitivity in the setting of chronic stress-induced elevation of GR-mediated signaling inherent in HIV infection. The further increased FKBP51 expression might lead to maladaptive stress response and HAND.