US FDA best practices for initiating early feasibility studies for neurological devices in the United States.

This article describes the efforts of the US Food and Drug Administration (FDA) Office of Neurological and Physical Medicine Devices to facilitate early clinical testing of potentially beneficial neurological devices in the US. Over the past 5 years, the FDA has made significant advances to this aim by developing early feasibility study best practices and encouraging developers and innovators to initiate their clinical studies in the US. The FDA uses several regulatory approaches to help start neurological device clinical studies, such as early engagement with sponsors and developers, in-depth interaction during the FDA review phase of a regulatory submission, and provision of an FDA toolkit that reviewers can apply to the most challenging submissions.

Postoperative Anticoagulation After Neurologic Surgery.

Management of anticoagulation and antiplatelet medications after neurosurgery can be complex, especially given that these patients have multiple medical comorbidities. In turn, neurosurgical patients are at high risk for the development of venous thromboembolism after surgery, so neurosurgeons must consider the use of pharmacologic prophylaxis. Developments in endovascular neurosurgery have produced therapies that require close management of antiplatelet medications to prevent postoperative complications. Any of these patient populations may need intrathecal access. This article highlights current strategies for managing these issues in the neurosurgical patient population.

Regulation of Neurological Devices and Neurointerventional Endovascular Approaches for Acute Ischemic Stroke.

The United States Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) is charged with ensuring patients in the US have timely access to high-quality, safe, and effective medical devices of public health importance. Within CDRH, the Division of Neurological and Physical Medicine Devices reviews medical technologies that interface with the central and peripheral nervous system (neurotechnologies), including neurointerventional medical devices that are used in the treatment of stroke. Endovascular treatments have demonstrated recent advances in reaching the marketplace and providing more options for patients with acute ischemic stroke and intracranial aneurysms specifically. Depending upon the pathway chosen for regulatory approval, and the evidentiary standard for different regulatory pathways, neurotechnologies can have well-established safety and effectiveness profiles, varying degrees of scientific and clinical uncertainty regarding safety and effectiveness, or when a humanitarian use exists, need only demonstrate a probable benefit and safety to the patient so potentially life-saving treatments can reach the marketplace. Reperfusion therapies have had specific advances in the treatment of stroke patients that originally had limited or no treatment options and for preventative treatments in providing care to patients with intracranial aneurysms to avoid potentially more catastrophic outcomes. Collaboration in multiple forums and environments will be important to continue to foster the neurointerventional technology sector and positively impact clinical medicine, from diagnosing and treating a neurological disorder, to potentially altering the progression of disease, and in many ways, contemporary approved devices have brought a new sense of hope and optimism that serious and otherwise disabling neurological diseases can be treated and in many cases cured with modern therapy. We present here the scope of FDA's regulatory landscape for neurological devices and neurointerventional endovascular approaches for acute ischemic stroke; this is essential information for those seeking to successfully translate medical device neurotechnologies for patient and consumer use.

Balloon-Occlusion Catheter Onyx Embolization of a Spinal Dural Arteriovenous Fistula Presenting with Subarachnoid Hemorrhage in a Pediatric Patient.

OBJECTIVE: Spinal dural arteriovenous fistulas (DAVFs) are insidious pathologies that, if left untreated, harbor potentially devastating consequences to the central nervous system. Spinal DAVFs are rare in the adult population and exceedingly uncommon in the pediatric population. In this report, we describe a spinal DAVF in a 3-year-old child whose initial presentation is subarachnoid hemorrhage (SAH). Balloon-test occlusion and balloon-catheter-assisted embolization of DAVF have not been previously described, and their advantages over alternative embolic and surgical techniques are discussed. METHODS: We performed a literature search on MEDLINE/PubMed to review current reports describing the epidemiology, clinical presentation, and treatment of spinal DAVFs. In this report, we describe a spinal DAVF in a 3-year-old child whose initial presentation is SAH. RESULTS: A spinal DAVF was diagnosed after deciding to image not only the brain but also the spine. Using a balloon-occlusion catheter, we confirmed that the DAVF arterial feeding vessel could be safely embolized. We then proceeded to effectively treat the DAVF with balloon-catheter-assisted Onyx-18 embolization. CONCLUSION: Based on our report and an analysis of the literature, we propose that pediatric patients presenting with nontraumatic SAH should undergo at least a magnetic resonance imaging of the brain and cervical spine as part of their initial workup. In addition, we describe a balloon-occlusion catheter embolization technique that allows not only excellent embolic penetration of the fistula but also prevention of microcatheter reflux and lessening of the need for a tedious plug-and-stack technique.

A murine model of hypertonic saline as a treatment for acute spinal cord injury: effects on autonomic outcome.

OBJECT: spinal cord injury (SCI) continues to be a problem without a definitive cure. Research based on improved understanding of the immunological aspects of SCI has revealed targets for treating and ameliorating the extent of secondary injury. Hypertonic saline (HTS), a substance both easy to create and to transport, has been investigated as an immunologically active material that can be used in a clinically relevant interval after injury. In this pilot study, HTS was investigated in a murine model for its abilities to ameliorate secondary injury after a severe spinal cord contusion. METHODS: female C57Bl/6 mice with severe T8-10 contusion injuries were used as the model subjects. A group of 41 mice were studied in a blinded fashion. Mice received treatments with HTS (HTS, 7.5%) or normal saline solution (NSS, 0.9%) at 2 discreet time points (3 and 24 hours after injury.) A separate group of 9 untreated animals were also used as controls. Animals were assessed for autonomic outcome (bladder function). In a group of 33 mice, histological assessment (cellular infiltration) was also measured. RESULTS: bladder function was found to be improved significantly in those treated with HTS compared with those who received NSS and also at later treatment times (24 hours) than at earlier treatment times (3 hours). Decreased cellular infiltration in each group correlated with bladder recovery. CONCLUSIONS: the increased effectiveness of later administration time of the more osmotically active and immunomodulatory substance (HTS) suggests that interaction with events occurring around 24 hours after injury is critical. These events may be related to the invasion of leukocytes peaking at 8-24 hours postinjury and/or the peak benefit time of subject rehydration.

The timing of carotid endarterectomy post stroke.

The timing of carotid endarterectomy (CEA) post stroke remains a controversial area. Most authorities have advocated waiting at least 2 to 6 weeks after stroke before performing a CEA. More recently, these recommendations have been challenged. This article reviews the background leading to advocacy of delayed CEA after stroke, current literature recommendations regarding CEA after subacute stroke, current literature regarding neuroradiologic imaging findings and their implications in decision making regarding CEA after stroke, and the role of CEA for stroke in evolution.

Small mammal MRI imaging in spinal cord injury: a novel practical technique for using a 1.5 T MRI.

The field of spinal cord injury research is an active one. The pathophysiology of SCI is not yet entirely revealed. As such, animal models are required for the exploration of new therapies and treatments. We present a novel technique using available hospital MRI machines to examine SCI in a mouse SCI model. The model is a 60 kdyne direct contusion injury in a mouse thoracic spine. No new electronic equipment is required. A 1.5T MRI machine with a human wrist coil is employed. A standard multisection 2D fast spin-echo (FSE) T2-weighted sequence is used for imaging the mouse. The contrast-to-noise ratio (CNR) between the injured and normal area of the spinal cord showed a three-fold increase in the contrast between these two regions. The MRI findings could be correlated with kinematic outcome scores of ambulation, such as BBB or BMS. The ability to follow a SCI in the same animal over time should improve the quality of data while reducing the quantity of animals required in SCI research. It is the aim of the authors to share this non-invasive technique and to make it available to the scientific research community.

The timing of carotid endarterectomy post stroke.

Despite the earlier accepted notion that CEA should be delayed 4 to 6 weeks after a stroke, current evidence suggests that CEA may be performed safely earlier than this in most patients who have mild to moderate deficits once symptoms stabilize. The gray areas, however, remain gray, as outlined. Crescendo TIAs are urgent cases in the authors' practice; others advocate a more moderate delayed approach in such cases. Almost everyone agrees that propagating intraluminal thrombus is treated best with a moderate delayed approach that allows the thrombus to resolve first with anticoagulants. Acute carotid occlusion must be assessed on an individual basis: cases that occlude under observation should be explored immediately; cases that come from the field with profound deficits have dismal outcomes, but even here surgery may be effective in salvaging a small group of good functional survivors, and the natural history without surgery is atrocious. Surgery for stroke in evolution is associated with higher morbidity and mortality rates; selected patients may benefit from emergency surgery. A final thought is that for patients who have routine TIA or small stroke, with minimal imaging evidence of infarction or mass effect, a stable deficit, and a normal level of consciousness, there is no reason to empirically delay carotid reconstruction, and patients are served best by a fast-track approach to surgical treatment.

Anterior approach to the subaxial cervical spine in children: a brief review.

Although it was originally developed to address degenerative problems, including disc herniations and cervical spondylotic myelopathy in the adult population, the anterior approach to the subaxial spine has proven to be useful for select indications in the pediatric population. The authors review indications for surgery, bone grafting, and instrumentation as they pertain to children.

Neuroendoscopy for spinal disorders: a brief review.

Neuroendoscopy has grown rapidly in the last 20 years as a therapeutic modality for treating a variety of spinal disorders. Spinal endoscopy has been widely used to treat patients with cervical, thoracic, and lumbosacral disorders safely and effectively. Although it is most commonly used with minimally invasive lumbar spine surgery, endoscopy has gained widespread acceptance for the treatment of thoracic disc herniations and for anterior release and rod implantation in the correction of thoracic spinal deformity. The authors review the use of endoscopy in spine surgery and in the treatment of spinal disorders as well as in the treatment of intrathoracic nonspinal lesions. Endoscopy has some significant advantages over open or other minimally invasive techniques in that it can allow for better visualization of the lesion, smaller incision sizes with reduced morbidity and mortality, reduced hospital stays, and ultimately lower cost. In addition, spinal endoscopy allows observers and operating room staff to be more involved in each case and fosters education. Spinal endoscopy, like any novel modality, carries with it additional risks and the surgeon must always be prepared to convert to an open procedure. The learning curve for spinal endoscopy is steep and the procedure should not be attempted alone by a novice surgeon. Nevertheless, with training and experience, the spine surgeon can achieve better outcomes, reduced morbidity, and better cosmesis with spinal endoscopy, and the operating times are comparable to open procedures. As technology evolves and more experience is obtained, neuroendoscopy will likely achieve further roles as a mainstay in spine surgery.

Request form history, clinical indication, and yield of brain magnetic resonance studies.

PURPOSE: To investigate whether improved clinical history allows the radiologist to better predict the pretest probability of obtaining a positive or negative result from a magnetic resonance (MR) examination. MATERIALS AND METHODS: Six neuroradiologists prospectively reviewed 100 consecutive requests for brain MR examinations and sequentially assessed 1) quality of written history, 2) degree of indication for requested study, and 3) any pertinent new information found during chart review that may have altered the degree of indication. MR yield was correlated with the degree of indication assessed before and after chart review. RESULTS: Most request form histories were judged as poor (63%), and chart review reduced the overall indications for MR examinations, as there was a tendency for high-indication requests to migrate to the low-indication category. Based on request form history alone, the yields for low- and high-indication studies were 13% and 37%, respectively. Correlations between MR yield and indication after chart review improved significantly (P < 0.05) with 2% and 61% for low and high indications, respectively. Sensitivity and specificity for a positive MR yield were 71% and 62%, respectively, for the indication judged by the request history alone, and 96% and 80%, respectively, after chart review. Positive and negative prediction rates were 37% and 87%, respectively, for the indication judged by the request history alone, and 61% and 98%, respectively, for the indication judged after chart review. CONCLUSION: Based on our limited data, most request form histories were inadequate, and essential information available in the chart before MR examinations was frequently missing from the request forms. When adequate information was provided, the indication for the studies as judged by the radiologists predicted the MR yield more accurately, particularly for those requests with low indication. Therefore, our study suggests that MR imaging (MRI) may be used more effectively when pertinent clinical history is available. However, our study is limited and further studies are needed to confirm our results.

Qualitative assessment of cervical spinal stenosis: observer variability on CT and MR images.

BACKGROUND AND PURPOSE: Several studies have been undertaken to validate quantitative methods of evaluating cervical spinal stenosis. This study was performed to assess the degree of interobserver and intraobserver agreement in the qualitative evaluation of cervical spinal stenosis on CT myelograms and MR images. METHODS: Cervical MR images and CT myelograms of 38 patients were evaluated retrospectively. Six neuroradiologists with various backgrounds and training independently assessed the level, degree, and cause of stenosis on either MR images or CT myelograms. Unknown to the evaluators, 16 of the patients were evaluated twice to determine intraobserver variability. RESULTS: Interobserver agreement among the radiologists with regard to level, degree, and cause of stenosis on CT myelograms showed kappa values of 0.50, 0.26, and 0.32, respectively, and on MR images showed kappa values of 0.60, 0.31, and 0.22, respectively. Intraobserver agreement with regard to level, degree, and cause of stenosis on CT myelograms showed mean kappa values of 0.69, 0.41, and 0.55, respectively, and on MR images showed mean kappa values of 0.80, 0.37, and 0.40, respectively. CONCLUSION: MR imaging and CT myelographic evaluation of cervical spinal stenosis by using current qualitative methods results in significant variation in image interpretation.