Occipital Nerve Stimulation and Sphenopalatine Ganglion Stimulation for Treatment of Intractable Headache Syndromes.

Headaches are an increasing cause of disability in the world. Intractable headache syndromes affect all age groups but predominantly the middle-aged, working population. Occipital neuralgia is a frequent comorbidity with intractable migraine headaches. Occipital nerve stimulation at the level of nuchal ridge is a reasonable option for these refractory patients. Ultrasound guidance of occipital nerve stimulation can optimize depth placement of leads. Revision surgeries of occipital nerve stimulation are usually performed using surgical leads. Cluster headaches and trigeminal autonomic cephalagias (TACs) are refractory headache conditions that are mediated by sphenopalatine ganglion. Sphenopalatine ganglion stimulation with infrazygomatic approach and fluoroscopic guidance of percutaneous leads can help alleviate pain from cluster headaches and TACs. Innovation in neurostimulation technologies have brought new optimism to these refractory conditions. Efficient and optimal delivery of neurostimulation for intractable headache syndromes requires a multidisciplinary team-based approach for long term compliance and efficacy.

Extended disease-free interval of 6 years in a recurrent glioblastoma multiforme patient treated with G207 oncolytic viral therapy.

BACKGROUND: Glioblastoma multiforme (GBM) is a relentless primary central nervous system malignancy that remains resistant to conventional therapy despite major advances in clinical neurooncology. This report details the case of a patient who had failed conventional treatment for recurrent GBM and was ultimately treated with a genetically engineered herpes simplex virus (HSV) type 1 vector, G207. METHODS: Case report detailing the outcomes of one patient enrolled into the gene therapy arm of the Neurovir G207 protocol whereby stereotactic injection of 120 µL G207 viral suspension containing 1×10(7) plaque-forming units (or active viral particles) was made into the enhancing region of the tumor. RESULTS: In this patient, despite aggressive surgical resection, adjuvant radiotherapy and chemotherapy, tumor progression occurred. However, with G207 oncolytic therapy and brief exposures to second and third treatments, this patient had an extended survival time of 7.5 years and a 6-year apparent disease-free interval, an extraordinarily unusual finding in the pretemozolomide era. CONCLUSION: With minimal adjunctive chemotherapy, including one course of temozolomide, one course of procarbazine, and four cycles of irinotecan, the patient survived over 7 years before the next recurrence. Addition of G207 to this patient's traditional therapy may have been the critical treatment producing her prolonged survival. This report demonstrates the potential for long-term response to a one-time treatment with oncolytic HSV and encourages continued research on oncolytic viral therapy for GBM.

Robert Bentley Todd's contribution to cell theory and the neuron doctrine.

Robert Bentley Todd, who is best remembered for "Todd's paralysis," made many more important contributions to neurology and neuroscience, including the concept of brain electricity and electrical discharges in epilepsy. He was also a pioneering microscopist and we here review his neurohistological studies and his contributions to the application of Schwann's (1839) cell theory to the nervous system and the later neuron doctrine, as described in his textbook The Descriptive and Physiological Anatomy of the Brain, Spinal Cord and Ganglions (Todd, 1845), his Cyclopaedia of Anatomy and Physiology (1847) and his joint textbook with William Bowman The Physiological Anatomy and Physiology of Man (1845). Writing in the mid-1840s, Todd acknowledged that the "vesicles" he observed corresponded to the earlier descriptions of "globules" or "kugeln" by Valentin and which Schwann first interpreted as cell bodies. Todd was among the first to recognize that nerve cell bodies were in continuity with axons ("axis cylinders"), sometimes associated with "the white substance of Schwann" ("tubular" fibers), or sometimes without ("gelatinous" fibers). He also described continuous nerve cell branching processes, later called dendrites. He was the first to recognize the insulating properties of Schwann's "white substance" (myelin) to facilitate conduction. Influenced by his contemporary, Faraday, Todd was also the first to develop the functional concept of dynamic polarization ("nervous polarity") to explain nerve cell conduction.

Early optical detection of cerebral edema in vivo.

OBJECT: Cerebral edema is a significant cause of morbidity and mortality in diverse disease states. Currently, the means to detect progressive cerebral edema in vivo includes the use of intracranial pressure (ICP) monitors and/or serial radiological studies. However, ICP measurements exhibit a high degree of variability, and ICP monitors detect edema only after it becomes sufficient to significantly raise ICP. The authors report the development of 2 distinct minimally invasive fiberoptic near-infrared (NIR) techniques able to directly detect early cerebral edema. METHODS: Cytotoxic brain edema was induced in adult CD1 mice via water intoxication by intraperitoneal water administration (30% body weight intraperitoneally). An implantable dual-fiberoptic probe was stereotactically placed into the cerebral cortex and connected to optical source and detector hardware. Optical sources consisted of either broadband halogen illumination or a single-wavelength NIR laser diode, and the detector was a sensitive NIR spectrometer or optical power meter. In one subset of animals, a left-sided craniectomy was performed to obtain cortical biopsies for water-content determination to verify cerebral edema. In another subset of animals, an ICP transducer was placed on the contralateral cortex, which was synchronized to a computer and time stamped. RESULTS: Using either broadband illumination with NIR spectroscopy or single-wavelength laser diode illumination with optical power meter detection, the authors detected a reduction in NIR optical reflectance during early cerebral edema. The time intervals between water injection (Time Point 0), optical trigger (defined as a 2-SD change in optical reflectance from baseline), and defined threshold ICP values of 10, 15 and 20 mm Hg were calculated. Reduction in NIR reflectance occurred significantly earlier than any of the ICP thresholds (p < 0.001). Saline-injected control mice exhibited a steady baseline optical signal. There was a significant correlation between reflectance change and tissue specific gravity of the cortical biopsies, further validating the dual-fiberoptic probe as a direct measure of cerebral edema. CONCLUSIONS: Compared with traditional ICP monitoring, the aforementioned minimally invasive NIR techniques allow for the significantly earlier detection of cerebral edema, which may be of clinical utility in the identification and thus early treatment of cerebral edema.

Short-term antifibrinolytic therapy before early aneurysm treatment in subarachnoid hemorrhage: effects on rehemorrhage, cerebral ischemia, and hydrocephalus.

BACKGROUND: Long-term administration of the antifibrinolytic agent epsilon aminocaproic acid (EACA) reduces the rate of rehemorrhage in patients with aneurysmal subarachnoid hemorrhage (SAH), but is associated with cerebral ischemia. OBJECTIVE: To evaluate short-term administration of EACA before early surgery in patients with SAH. METHODS: Retrospective review of 356 patients admitted between June 2002 and December 2007 with a diagnosis of aneurysmal SAH. Medical records were reviewed to determine SAH risk factors, clinical grade at the time of admission, and incidence of rehemorrhage, permanent new-onset focal neurological deficits, computed tomography evidence of cerebral infarction, symptomatic vasospasm, and hydrocephalus. RESULTS: Patients underwent treatment of the ruptured aneurysm an average of 47.4 hours after admission and received an average total dose of 40.6 g of EACA. The mean length of time of administration of EACA was 35.6 hours. There was a total of 5 rehemorrhages, for an overall rebleeding rate of 1.4% and a rate of rehemorrhage per 24-hour period of 0.71%. Overall, the rates of symptomatic vasospasm and permanent neurological deficits attributable to ischemic stroke were 11.5% and 7.2%, respectively, and the incidence of shunt-dependent hydrocephalus was 42.3%. Patients who were treated with coiling had higher rates of symptomatic vasospasm and ischemic complications than patients who had surgery. CONCLUSION: Short-term administration of EACA is associated with rates of rehemorrhage, ischemic stroke, and symptomatic vasospasm that compare favorably with historical controls. The rate of hydrocephalus is relatively high and may be attributable to EACA treatment.

Localization of angiopoietin-1 and Tie2 immunoreactivity in rodent ependyma and adjacent blood vessels suggests functional relationships.

Angiopoietin-1 (Angpt1; previously Ang-1) participates in vascular maintenance and remodeling. In the current study, we investigated the distribution of Angpt1 protein in rat brain. We detected Angpt1 immunoreactivity (IR) in cerebral blood vessels, cuboidal ependyma, and tanycytes, which are specialized hypothalamic bipolar ependymal cells. We also evaluated patterns of IR of endothelium-specific receptor tyrosine kinase 2 (Tie2, the receptor for Angpt1). Tie2 IR was present in Angpt1-immunoreactive cuboidal ependyma in a membranous pattern, suggesting an autocrine or paracrine role for Angpt1-Tie2. Tie2 IR was also associated with peri-ependymal blood vessels, some of which were contacted by tips of Angpt1-immunoreactive tanycyte processes, implying a potential functional ligand-receptor interaction mediating communication between the cerebrospinal fluid and vascular compartments. Because we previously found that cerebral Angpt1 expression was modulated by 17beta-estradiol (E2), and because some tanycyte functions are modulated by E2, we tested the hypothesis that E2 affects ependymal and tanycyte Angpt1 expression in vivo. No gross E2 effect on the ependymal pattern of Angpt1 IR or cerebral Angpt1 protein content was observed.

Tumor-associated epilepsy.

Tumor-associated epilepsy is an important contributor to morbidity in patients with brain tumors. Proposed pathophysiological mechanisms to explain these effects range from neuronal and glial dysfunction to deranged vascular homeostasis, to ionic and pH changes. Perilesional tissue alterations play a vital role in the generation of tumor-associated seizures. Clinical studies have determined that tumor-associated seizures are usually focal with secondary generalization and often resistant to antiepileptic drugs. Tumor histopathological characteristics and location are independent factors that impact seizure burden. Further understanding of the mechanisms of tumor-associated epilepsy may lead to new types of treatments targeted at perilesional tissue alterations.

Estradiol augments peri-infarct cerebral vascular density in experimental stroke.

Peri-infarct increase of vascular density has been observed in animals and in humans with ischemic stroke. Increased peri-infarct vascular density correlates with improved functional outcome after stroke. We hypothesized that pre-treatment with estradiol will increase post-ischemic peri-infarct capillary density in a rat model of transient ischemic stroke. Estradiol, compared to placebo, augmented post-ischemic peri-infarct vascular density by 22% 10 days after stroke. Recovery of forelimb function was not improved with estradiol treatment on day three and nine post-stroke. Loss of estradiol may limit repair in the peri-infarct region by limiting angiogenesis, but functional significance in stroke recovery requires further investigation.