Molecular hydrogen therapy for neurological diseases: a review of current evidence.

Reactive oxygen species and other free radicals cause oxidative stress which is the underlying pathogenesis of cellular injury in various neurological diseases. Molecular hydrogen therapy with its unique biological property of selectively scavenging pathological free radicals has demonstrated therapeutic potential in innumerable animal studies and some clinical trials. These studies have implicated several cellular pathways affected by hydrogen therapy in explaining its anti-inflammatory and antioxidative effects. This article reviews relevant animal and clinical studies that demonstrate neuroprotective effects of hydrogen therapy in stroke, neurodegenerative diseases, neurotrauma, and global brain injury.

Management of a ruptured and unruptured pial arteriovenous fistula during and after pregnancy.

We present the case of a 16-week pregnant 19-year-old female who presented with hemiplegia due to a ruptured right frontal pial arteriovenous fistula (PAVF). She was also found to have an unruptured right temporal PAVF and a family history of brain hemorrhage. The patient was managed with Onyx embolization of the ruptured fistula, followed by surgical excision and hematoma evacuation. At 35 weeks gestation, she underwent cesarean section to prevent rupture of the second fistula in the setting of peripartum hypervolemia and increasing headaches. The child was delivered healthy. Subsequently, the right temporal AV fistula, supplied by a middle cerebral artery and posterior cerebral artery branch, underwent staged embolization resulting in complete occlusion. The patient recovered to a modified Rankin score of two, with a left foot drop as only persistent significant motor deficit.

Intracranial Venous Sinus Stenting in Idiopathic Intracranial Hypertension: A Case Report and Review of the Literature.

We describe a case of severe headaches, double vision, and progressive vision loss secondary to a ruptured intracranial cyst (IAC) in a 31-year-old woman with no relevant past medical history. The case is peculiar because drainage of the subdural hygroma led to a minimal improvement in vision with persistent elevated intracranial pressure (ICP). Further exploration revealed transverse sinus stenosis necessitating stenting. Evaluation post-stenting showed marked reduction of ICP and improvement in symptoms. This report underscores the importance of comprehensive work-up and suspicion of multiple underlying etiologies that may be crucial to complete resolution of presenting symptoms in some cases. We provide an overview of the clinical indications and evidence for venous sinus stenting in treating idiopathic intracranial hypertension (IIH).

Mechanical Thrombectomy for Sequential Bilateral Middle Cerebral Artery Occlusions in a Patient With Recurrent Cryptogenic Strokes: A Case Report.

Recurrent sequential mechanical thrombectomy for cryptogenic large vessel occlusion (LVO) can lead to excellent clinical outcome. A 68-year-old right-handed male presented with an acute proximal right middle cerebral artery (MCA) ischemic syndrome and underwent successful revascularization by mechanical thrombectomy with normal functional recovery. He was treated with dual antiplatelet therapy for 2 months following discharge, however later discontinued clopidogrel due to side effects. He then developed a recurrent, contralateral MCA occlusion 16 months later and once again received emergent endovascular reperfusion therapy with excellent neurological outcome. He has remained on off-label empiric oral anticoagulation since and has not had recurrent stroke nor evidence of cerebral ischemia. Favorable clinical outcomes can be achieved in patients despite recurrent LVO who underwent emergent mechanical thrombectomy. Optimal antithrombotic secondary stroke prevention strategies following embolic stroke of unknown source remains uncertain as recent evidence does not support rivaroxaban or dabigatran over aspirin. The benefit of apixaban over aspirin for the prevention of recurrent cerebral ischemia is under current investigation.

Review of Atypical and Anaplastic Meningiomas: Classification, Molecular Biology, and Management.

Although the majority of meningiomas are slow-growing and benign, atypical and anaplastic meningiomas behave aggressively with a penchant for recurrence. Standard of care includes surgical resection followed by adjuvant radiation in anaplastic and partially resected atypical meningiomas; however, the role of adjuvant radiation for incompletely resected atypical meningiomas remains debated. Despite maximum treatment, atypical, and anaplastic meningiomas have a strong proclivity for recurrence. Accumulating mutations over time, recurrent tumors behave more aggressively and often become refractory or no longer amenable to further surgical resection or radiation. Chemotherapy and other medical therapies are available as salvage treatment once standard options are exhausted; however, efficacy of these agents remains limited. This review discusses the risk factors, classification, and molecular biology of meningiomas as well as the current management strategies, novel therapeutic approaches, and future directions for managing atypical and anaplastic meningiomas.

The anterior incisural width as a preoperative indicator for intradural space evaluation: An anatomical investigation.

BACKGROUND: The opticocarotid triangle (OCT) and the carotico-oculomotor triangle (COT) are two anatomical triangles used in accessing the interpeduncular region. Our objective is to evaluate if the anterior incisural width (AIW) is an indicator to predict the intraoperative exposure through both triangles. METHODS: Twenty sides of 10 cadaveric heads were dissected and analyzed. The heads were divided into the following: Group A - narrow anterior incisura and Group B - wide anterior incisura - using 26.6 mm as a cutoff distance of the AIW. Subsequently, the area of the COT and the OCT in the transsylvian approach was measured, along with the maximum widths through the two trajectories in modified superior transcavernous approach. RESULTS: The COT in the wide group was shown to have a significantly larger area compared with the COT in the narrow group (38.4 ± 12.64 vs. 58.3 ± 15.72 mm, P < 0.01). No difference between the two groups was reported in terms of the area of the OCT (50.9 ± 19.22 mm vs. 63.5 ± 15.53 mm, P = 0.20), the maximum width of the OCT (6.6 ± 1.89 vs. 6.5 ± 1.38 mm, P = 1.00), or the maximum width of the COT (11.7 ± 2.06 vs. 12.2 ± 2.32 mm, P = 0.50). Clinical cases were included. CONCLUSION: An AIW <26.6 mm is an unfavorable factor related to a limited COT area in a transsylvian approach for pathologies at the interpeduncular fossa. Preoperative identification and measurement of a narrow AIW can suggest the need to add a transcavernous approach.

Combined petrosal approach for resection of petroclival chondrosarcoma: Microsurgical 2-D video.

BACKGROUND: Petroclival lesions pose a significant neurosurgical challenge due to involvement or close proximity to important neurovascular structures. Chondrosarcomas are rare lesions that can affect these areas. CASE DESCRIPTION: A 24-year-old male with 3 months history of poor coordination, imbalance, left-sided face hypoesthesia, facial palsy House-Brackmann Grade 2, and 6th cranial nerve palsy with diplopia. Hearing was preserved. Preoperative images showed a 5.5 cm multilobulated enhancing extra-axial mass centered in the left petroclival region with extension into middle and posterior fossa causing severe (Stage 3) brainstem compression.[1] After a lengthy discussion of treatment options, the patient consented for the procedure. We performed a presigmoid retrolabyrinthine combined petrosal approach. We used cranial nerves monitoring (VII, VIII, IX, X, XI, XII), frameless stereotaxy, and a lumbar drain. Due to the tumor size and location (petroclival region with extension into the posterior and middle cranial fossa), we chose this approach to achieve a maximal safe resection of the tumor and preserve hearing. Alternative approaches of use are expanded middle fossa with transcavernous extension or expanded endonasal approach. The selected approach achieved wide exposure of the tumor which was highly vascular. The tumor was carefully dissected off the brainstem, cranial nerves (IV, V, VI, VII, VIII), and basilar artery trunk. A gross total resection was achieved (Multimedia 1). The patient did well after surgery and was extubated on postoperative day (POD) 1 and the lumbar drain removed on POD 5. Pathology reported low-grade chondrosarcoma (WHO grade I). At 3 months follow-up, the patient improved neurologically, including facial nerve weakness (House-Brackmann Grade 1) except for his left 6th cranial nerve palsy which mildly improved. CONCLUSION: Petroclival chondrosarcomas are rare tumors that are usually treated with surgical resection followed by stereotactic radiosurgery. The tumor size, location, and extension dictate approach selection. For lesions involving the petroclival region with extension into the middle fossa and posterior fossa, the combined petrosal approach is reasonable.

Optimizing Radiosurgery for Trigeminal Neuralgia: Impact of Radiation Dose and Anatomic Target on Patient Outcomes.

OBJECTIVE: Radiosurgery is an increasingly popular treatment for trigeminal neuralgia (TN); however, several treatment variables require further study. This meta-analysis was conducted to clarify ambiguity in the literature and optimize treatment parameters. METHODS: A random-effects proportions meta-analysis using subgroup analysis and meta-regression investigated the association of prescription dose and anatomic target on outcomes in patients with typical TN. The PRISMA guidelines were used. Radiation doses used ranged from 70 to 90 Gy and the anatomic targets were either the root entry zone or a more distal nerve location. Outcome measures were pain at last follow-up and the development of bothersome numbness. RESULTS: Increasing radiation prescription dose was associated with improved outcomes across all analyzed doses (P < 0.001). Patients treated at a distal trigeminal nerve target had better pain control compared with a root entry zone target (P < 0.001). Despite a higher median dose, a distal target was independently associated with improved pain control. There were similar rates of bothersome numbness across radiation doses and both treatment targets. CONCLUSIONS: Higher radiation dose was associated with superior pain control without increasing bothersome numbness. Independent of dose, the distal target was also associated with improved pain control. Bothersome numbness was not related to dose or target.

Tailoring the surgical corridor to the basilar apex in the pretemporal transcavernous approach: morphometric analyses of different neurovascular mobilization maneuvers.

BACKGROUND: The pretemporal transcavernous approach (PTA) provides optimal exposure and access to the basilar artery (BA); however, the PTA can be invasive when vital neurovascular structures are mobilized. The goal of this study was to evaluate mobilization strategies to tailor approaches to the BA. METHODS: After an orbitozygomatic craniotomy, 10 sides of 5 cadaveric heads were used to assess the surgical access to the BA via the opticocarotid triangle (OCT), carotid-oculomotor triangle (COT), and oculomotor-tentorial triangle (OTT). Measurements were obtained, and morphometric analyses were performed for natural neurovascular positions and after each stepwise expansion maneuver. An imaginary line connecting the midpoints of the limbus sphenoidale and dorsum sellae was used as a reference to normalize the measurements of BA exposure and to facilitate the clinical applicability of this technique. RESULTS: In the OCT, the exposed BA segment ranged from - 1 ± 3.9 to + 6 ± 2.0 mm in length in its natural position. In the COT, the accessible BA segment ranged from - 4 ± 2.3 to - 2 ± 3.0 mm in length in its natural position. Via the OTT, the accessible BA segment ranged from - 7 ± 2.6 to - 5 ± 2.8 mm in length in its natural position. In the OCT, COT, and OTT, a posterior clinoidectomy extended the exposure down to - 6 ± 2.7, - 8 ± 2.5, and - 9 ± 2.9 mm, respectively. CONCLUSIONS: This study quantitatively evaluated the need for the expansion maneuvers in the PTA to reach BA aneurysms according to the patient's anatomical characteristics.

High flow bypass for right giant cavernous internal carotid artery aneurysm with fibromuscular dysplasia of cervical internal carotid artery: microsurgical 2-D video.

BACKGROUND: It is well known that intracranial aneurysms can be associated to fibromuscular dysplasia (FMD). Nevertheless, it is not clear the best treatment strategy when there is an association of giant symptomatic cavernous carotid aneurysm with extensive cervical internal carotid artery (ICA) FMD. CASE DESCRIPTION: We present the case of 63 year-old right-handed female with hypothyroidism, 1 month history of right-sided pulsatile headache and visual disturbances with feeling of fullness sensation and blurry vision. Her neurological exam showed partial right oculomotor nerve palsy with mild ptosis, asymmetric pupils (right 5 mm and left 3mm, both reactive), and mild exotropia, normal visual acuity. Computed tomography angiogram and conventional angiogram showed 2.5 × 2.6 × 2.6 cm non-ruptured aneurysm arising from cavernous segment of the right ICA. She had right hypoplastic posterior communicant artery, and collateral flow through anterior communicant artery during balloon test occlusion and the presence of right cervical ICA FMD. The patient was started on aspirin. After lengthy discussion of treatment options in our neurovascular department, between observations, endovascular treatment with flow diverter device, or high flow bypass, recommendation was to perform high flow bypass and patient consented for the procedure. We performed right-sided pterional trans-sylvian microsurgical approach and right neck dissection at common carotid bifurcation under electrophysiology monitoring (somatosensory evoked potentials and electroencephalography); while vascular surgery department assisted with the radial artery graft harvesting. The radial artery graft was passed through preauricular tunnel, cranially was anastomosed at superior trunk of middle cerebral artery, and caudally at external carotid artery (Video). Intraoperative angiogram showed adequate bypass patency and lack of flow within aneurysm. The patient was extubated postoperatively and discharged home with aspirin in postoperative day 5. Improvement on oculomotor deficit was complete 3 weeks after surgery. CONCLUSION: Nowadays, endovascular therapy can manage small to large cavernous ICA aneurysms even if associated to FMD, although giant symptomatic cavernous carotid aneurysms impose a different challenge. Here, we present the management for the association of symptomatic giant cavernous ICA aneurysm and cervical ICA FMD with high flow bypass. We consider important to keep the skills in the cerebrovascular neurosurgeon armamentarium for the safe management of these lesions.

Headache Relief Is Maintained 7 Years After Anterior Cervical Spine Surgery: Post Hoc Analysis From a Multicenter Randomized Clinical Trial and Cervicogenic Headache Hypothesis.

OBJECTIVE: To evaluate whether anterior cervical spine surgery offers sustained (7 years) relief in patients with cervicogenic headaches (CGHs), and evaluate the difference between cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) for 1 and 2-level surgeries from a multicenter randomized clinical trial. METHODS: A post hoc analysis was performed of 575 patients who underwent one or 2-level CDA or ACDF for symptomatic cervical spondylosis as part of a prospective randomized clinical trial. Assessment of pain and functional outcome was done with the Neck Disability Index (NDI) in the trial. We used the NDI headache component to assess headache outcome. RESULTS: For both 1- and 2-level CDA and ACDF groups, there was significant headache improvement from preoperative baseline out to 7 years (p < 0.0001). For 1-level surgeries, headache improvement was similar for both groups at the 7-year point. For 2-level treatment, CDA patients had significantly improved headache scores versus ACDF patients at the 7-year point (p = 0.016). CONCLUSION: The headache improvement noted at early follow-up was sustained over the long-term period with ACDF and CDA populations. In the case of 2-level operations, CDA patients demonstrated significantly greater benefit compared to ACDF patients over the long-term. Sinuvertebral nerve irritation at the unco-vasculo-radicular junction and anterior dura may be the cause of CGH. Therefore, it is possible that improved cervical kinematics and preservation of range of motion at adjacent uncovertebral joints in CDA may contribute to the observed difference between the groups.

Stem and progenitor cell microenvironment for bone regeneration and repair.

Stem cells reside in their native microenvironment, which provides dynamic physical and chemical cues essential to their survival, proliferation and function. A typical cell-based therapeutic approach requires the mesenchymal stem cells (MSC) to depart their native microenvironment, transplant to in-vivo environment, differentiate toward multiple lineages and participate in bone formation. The long-term survival, function and fate of MSC are dependent on the microenvironment in which they are transplanted. Transplantation of morselized autologous bone, which contains both stem cells and their native microenvironment, results in a good clinical outcome. However, implantation of bone graft substitutes does not provide the complete and dynamic microenvironment for MSC. Current bone graft therapeutics may need to be improved further to provide an optimal engineered MSC microenvironment.

Disseminated Coccidioidomycosis to the Spine-Case Series and Review of Literature.

Coccidioidomycosis is a fungal infectious disease caused by the Coccidioides species endemic to Southwestern United States. Symptomatic patients typically present as community-acquired pneumonia. Uncommonly, in about 1% of infections, hematogenous extra pulmonary systemic dissemination involving skin, musculoskeletal system, and meninges occur. Disseminated spinal infection is treated with antifungal drugs and/or surgical treatment. A retrospective review of medical records at our institution was done between January 2009 to December 2018 and we present three cases of spinal coccidioidomycosis and review the current literature. Disseminated coccidioidomycosis can lead to spondylitis that can present as discitis or a localized spinal or paraspinal abscess. Spinal coccidioidomycosis is typically managed with antifungal treatments but can include surgical treatment in the setting poor response to medical therapy, intractable pain, presence of neurological deficits due to compression, or structural spinal instability.

DuraSeal Exact Is a Safe Adjunctive Treatment for Durotomy in Spine: Postapproval Study.

STUDY DESIGN: A nonrandomized, two-armed prospective study. OBJECTIVE: Water-tight dural closure is paramount to the prevention of cerebrospinal fluid (CSF) leakage and associated complications. Synthetic polyethylene glycol (PEG) hydrogel has been used as an adjunct to sutured dural repair; however, its expansion postoperatively is a concern for neurological complications. A low-swell formulation of PEG sealant was introduced as DuraSeal Exact Spine Sealant System (DESS). A Post-Approval Study was performed primarily to evaluate the safety and efficacy of DESS for spinal dural repair compared to current alternatives, in a large patient population, reflecting a real-world practice. METHODS: A total of 36 sites in the United States enrolled 429 patients treated with DESS as an adjunct to dural repair in the spinal sealant group and 406 patients treated with all other modalities in the control arm, from October 2011 to June 2016. The primary endpoint was the incidence of CSF leak within 90 days of operation. The secondary endpoints evaluated were deep surgical site infection and neurological serious adverse events. RESULTS: The CSF leakage in the DESS group (6.6%) was not significantly different from the control group (6.5%) (p = .83), and there was no significant difference in the time to first leak. The two groups had no significant differences in deep surgical site infection (1.6% versus control 2.1%, p = .61) or proportion of subjects with neurological serious adverse events (2.9% versus control 1.6%, p = .516). CONCLUSIONS: DuraSeal Exact Spinal Sealant is safe when compared to current alternatives for spinal dural repair.

Adult Thoracic Intradural Exophytic Mature Teratoma: Case Report and Literature Review.

Mature thoracic intraspinal teratomas are rare tumors in adults. In this case study, we present a case of intradural, extramedullary teratoma, which was surgically resected. A 50 year old man presented with progressive bilateral leg pain, severe myelopathy and weakness. Magnetic Resonance Imaging (MRI) revealed a cystic mass lesion in the T11-12 region region. Microsurgical resection of the tumor using CO2 laser with neuromonitoring was performed. Postoperatively, the patient had a remarkable clinical improvement. Mature spinal teratomas are rare, slow growing spinal tumors. Surgical resection provides excellent recovery, and recurrence rates are low.

Radial Artery Bypass for Intractable Vertebrobasilar Insufficiency: Case Series and Review of the Literature.

BACKGROUND: Vertebrobasilar insufficiency resulting from embolism, atherosclerosis, or arterial dissection has long been a challenge for successful management and outcomes. The main treatment options include medical therapy, angioplasty and stenting, and surgical revascularization. Unlike cardiac or peripheral vascular revascularization, large randomized trials with cerebrorevascularization have not revealed favorable outcomes. In patients who have failed maximal medical therapy, and having persistent debilitating symptomology, cerebral revascularization may still be a viable option. METHODS: We report 3 patients who presented with symptoms of vertebrobasilar ischemia. The diagnosis was verified by computerized tomographic arteriography and digital subtraction angiography. RESULTS: These patients subsequently underwent revascularization with a radial artery graft. We also present a comprehensive review of the literature of treatment for vertebrobasilar insufficiency. CONCLUSIONS: Surgical revascularization should be considered in the posterior circulation in the rare subset of patients with VBI, who remain symptomatic despite having a protracted course of maximal medical therapy with large- and medium-sized vessel occlusions and poor collateral circulation.

Management of spinal epidural arteriovenous fistulas: interventional techniques and results.

BACKGROUND: Spinal epidural arteriovenous fistulas (SEDAVF) are rare and poorly understood clinical entities. MATERIALS AND METHODS: We report a series of five (three men, two women) consecutive cases treated at our center to analyze their characteristic and treatment strategies in their management. We report a successful technique of percutaneous embolization of fistulas in a patient with failed previous attempts. RESULTS: All five patients were symptomatic; three patients presented with a history of back pain, which progressed to myelopathic symptoms, one patient had symptoms of persistent back pain, and one patient had intermittent numbness of the left arm and thigh. Of the three patients who had myelopathic symptoms, two were successfully treated with transarterial embolizations with Onyx copolymer. The third patient who had a prominent epidural venous pouch with numerous arterial feeders was embolized percutaneously with a flat detector CT guided navigation (XperCT) and real time fluoroscopic monitoring of the injected n-butyl cyanoacrylate glue, after previous unsuccessful attempts with surgery and arterial embolizations. All three myelopathic treated patients had complete angiographic remission of the fistulas and symptoms on follow-up (mean 7.2 months). CONCLUSIONS: The diagnosis and treatment of SEDAVF can be challenging due to their rarity and intricate pathomechanics. Patients with severe pain or progression of symptoms or myelopathic symptoms need to be treated at the earliest opportunity, while asymptomatic patients can be closely monitored. Percutaneous embolization is an effective strategy to embolize SEDAVF associated venous pouch.

Tibial artery autografts: alternative conduits for high flow cerebral revascularizations.

BACKGROUND: Extracranial-to-intracranial (EC-IC) bypass is a valuable tool in treating intracranial diseases requiring flow replacement or parent vessel sacrifice. Radial artery grafts (RAGs) and saphenous vein grafts (SVGs) have been used as conduits to provide adequate high flow revascularizations. It is a therapeutic challenge when these grafts are unavailable. METHODS: All EC-IC high flow cerebral revascularizations performed using conduits other than RAGs or SVGs were identified from a prospective cerebrovascular registry. These patients were retrospectively reviewed for surgical technique, graft patency, graft flow, and clinical outcomes. RESULTS: Three patients (all women) underwent EC-IC bypass surgery using tibial artery grafts (two anterior tibial artery and one posterior tibial artery) because of the nonavailability of RAG or SVG. The two anterior tibial artery graft bypasses were patent with good flow at 8 and 3 months. The posterior tibial artery graft occluded intraoperatively. None of the patients developed vascular complications in the lower extremity due to tibial artery harvest. CONCLUSIONS: Tibial arteries are safe, contingent alternatives to conventional conduits for performing high flow cerebral revascularizations and conduit reconstructions.

Surgical resection of cavernous malformations of the brainstem: evolution of a minimally invasive technique.

OBJECTIVE: The purpose of this study is to provide an institutional retrospective review of surgically treated brainstem cavernous malformations. METHODS: Between 2005 and 2010, 22 consecutive patients with brainstem cavernous malformations (15 female and 7 male) with a mean age of 43 years underwent surgical treatment. Mean volume of the resected cavernous malformations was 0.65 cm(3). A minimally invasive resection technique was used for these cases, in conjunction with skull base approaches. RESULTS: The mean follow-up period was 26.6 months (range, 4-68 months). Of the 22 patients, 9% did not have clear evidence of hemorrhage at the time of presentation. Of the remainder, 22% had two or more instances of hemorrhage documented by magnetic resonance imaging. After resection and during follow-up, 54% of patients had an improvement in their modified Rankin scale, whereas 14% were worse compared with their preoperative presentation; 32% were unchanged and 9% of patients were found to have residual cavernoma post-surgery. CONCLUSION: Our longitudinal experience has guided us to emphasize minimally invasive approaches during resection of the brainstem cavernous malformations, occasionally at the expense of achieving a complete resection, to improve patient outcomes.

Petrous bone epidermoid cyst caused by penetrating injury to the external ear: Case report and review of literature.

Epidermoid cysts are histologically benign, slow-growing congenital neoplasms of the central nervous system that may arise from retained ectodermal implants. The epidermoid lesions are generally caused during the 3(rd) to 5(th) week of gestation by an incomplete cleavage of the neural tissue from the cutaneous ectoderm, though it can also happen later in life due to introduction of skin elements by skin puncture, trauma or surgery. We present this unique case of a petromastoid epidermoid cyst associated with ipsilateral cerebellar abscesses, presenting 20 years after a penetrating trauma to the external auditory canal. Radical excision of both lesions and revision of the previous fistulous tract was performed. We present the diagnostic challenge and the operative treatment of this unique case, which to our knowledge is the first where an epidermoid cyst and an adjacent brain abscess occurred as a result of a single traumatic event.