A Phase 2 Randomized, Sham-Controlled Trial of Internal Carotid Artery Infusion of Autologous Bone Marrow-Derived ALD-401 Cells in Patients With Recent Stable Ischemic Stroke (RECOVER-Stroke).

BACKGROUND: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow-derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy. METHODS: This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications. RESULTS: There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, -0.3 to 0.8; P=0.330). There were no significant differences between the groups on any of the secondary efficacy measures. CONCLUSIONS: Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01273337.

The Effectiveness and Risks of Fluoroscopically-Guided Cervical Medial Branch Thermal Radiofrequency Neurotomy: A Systematic Review with Comprehensive Analysis of the Published Data.

OBJECTIVE: To determine the effectiveness and risks of fluoroscopically-guided cervical medial branch thermal radiofrequency neurotomy (CMBTRFN) for treating chronic neck pain of zygapophysial joint origin. DESIGN: Systematic review of the literature with comprehensive analysis of the published data. INTERVENTIONS: Four reviewers formally trained in evidence-based medicine searched the literature on CMBTRFN. Each assessed the methodologies of studies found and appraised the quality of evidence presented. OUTCOME MEASURES: The primary outcomes assessed were 100% relief of pain 6 and 12 months after treatment. Other outcomes were noted if reported. The evidence was evaluated in accordance with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. RESULTS: The searches yielded eight primary publications on the effectiveness of the procedure. The evidence shows a majority of patients were pain free at 6 months and over a third were pain free at 1 year. The number needed to treat for complete pain relief at 6 months is 2. The evidence of effectiveness is of high quality according to the GRADE system. Twelve papers were found reporting unwanted effects, most of which are minor and temporary. No serious complications have ever been reported from procedures performed according to the published guidelines. The evidence of risks is of low quality according to the GRADE system. CONCLUSIONS: If performed as described in the International Spine Intervention Society Guidelines, fluoroscopically-guided CMBTRFN is effective for abolishing zygapophysial joint pain and carries only minor risks.

Feasibility and effectiveness of telehealth in the management of cervicothoracic and lumbar pain during the first six months of the SARS-CoV-2 pandemic: A case series.

Objectives: The primary study objective is to assess the effectiveness and utility of telehealth in managing spine pain. The secondary objective is to evaluate the feasibility of employing various treatments utilizing telehealth. Study design: Retrospective case series of patients with spinal pain managed primarily by telehealth during the first 6 months of the SARS-CoV-2 pandemic in the United States. Setting: A single center community based out-patient clinic and ambulatory surgical facility. Subjects: 101 consecutive adult patients complaining of cervicothoracic or low back pain presenting to a specialized spine clinic. Methods: Telehealth was the preferred method of consultation for 101 consecutive patients presenting with cervicothoracic and/or low-back pain. After conservative care, patients with continued pain and disability were offered procedures. Disability Index (NDI and ODI) and pain Visual Analog Scores (VAS) were used to determine patient outcomes. Results: 101 new out-patient consultations occurred. Telehealth initial consultation occurred in 98% of cases. There was a total of 504 follow up consultations. Follow up was via telehealth in 69%. Significant neurological abnormalities were detected by telehealth in 3% of patients. The lost to follow up rate was 10%. All 63 interventional procedures performed on 42 patients were completed as planned during telehealth visits. Likewise for all 9 surgical procedures. Outcomes were monitored via telehealth. Overall, for patients with cervicothoracic pain, minimal clinically important differences (MCID) for VAS or NDI were reached in 71%. Overall, the MCID for VAS or ODI for low back pain patients was reached in 70%. Conclusion: Telehealth in our series was easily deployable, highly feasible, allowed accurate monitoring of patient care and resulted in accurate triaging for interventions and surgery. Overall patient outcomes compare favorably with that reported for in-person spinal pain care. Telehealth was effective and easily utilizable.

Evolving minimally invasive spine surgery: a surgeon's perspective on technological convergence and digital or control system.

Degenerated spinal disc and spinal stenosis are common problems requiring decompressive spinal surgery. Traditional open spinal discectomy is associated with significant tissue trauma, greater morbidity/complications, scarring, often longer term of convalescence, and even destabilization of the spine. Therefore, the pursuit of less traumatic minimally invasive spine surgery (MISS) began. The trend of spinal surgery is rapidly moving toward MISS. MISS is a technologically dependent surgery, and requires increased utilization of advanced endoscopic surgical instruments, imaging-video technology, and tissue modulation technology for performing spinal surgery in a digital operating room (DOR). It requires seamless connectivity and control to perform the surgical procedures in a precise and orchestrated manner. A new integrated DOR, the technological convergence and control system SurgMatix(R), was created in response to the need and to facilitate MISS with "organized control instead of organized chaos" in the endoscopic OR suite. It facilitates the performance, training, and further development of MISS.

Extent of intra-arterial calcification on head CT is predictive of the degree of intracranial atherosclerosis on digital subtraction angiography.

BACKGROUND: Intracranial intra-arterial calcifications (ICAC) are a common finding on head CT examinations, but their significance is not known. The aim of this study is to determine if a relationship exists between ICAC on head CT and the presence of a high-grade atherosclerotic stenosis on cerebral angiography. METHODS: This was a retrospective study of 108 consecutive patients admitted to the stroke service at Parkland Hospital in Dallas, Tex., USA. Each patient had undergone a head CT and catheter-based angiographic study to meet the inclusion criteria. Demographic information was recorded along with CT imaging data in regards to the amount of calcification. Angiographic images were reviewed independently, and a comparison was made to determine if calcification was predictive of finding a high-grade stenosis on angiography. RESULTS: A total of 108 consecutive patients with a mean age of 56 +/- 12 years were studied. Of the 540 vessels studied, 65 (12%) were found to have a stenosis of >or=50% on angiography, and 71 (13.1%) were found to have a calcium grade of 3 or 4 on head CT. ICAC appeared to be more common in the anterior circulation compared to the posterior circulation. Patients with grade 3 or 4 calcification of an intracranial vessel on head CT were more likely to have a stenosis of >or=50% on cerebral angiography. CONCLUSIONS: The presence of ICAC on head CT appears to correlate with the presence of an underlying intracranial stenosis on angiography. Further study is required to validate these preliminary findings.

Spontaneous spinal cerebrospinal fluid leak as a cause of coma after craniotomy for clipping of an unruptured intracranial aneurysm.

Spontaneous spinal CSF leaks are best known as a cause of orthostatic headache, but may also be the cause of coma. The authors encountered a unique case of a spontaneous spinal CSF leak causing coma 2 days after craniotomy for clipping of an unruptured aneurysm. This 44-year-old woman with autosomal dominant polycystic kidney disease underwent an uneventful craniotomy for an incidental anterior choroidal artery aneurysm. No intraoperative spinal CSF drainage was used. Two days after surgery the patient became comatose with a left oculomotor nerve palsy. Computed tomography scanning revealed a right extraceberal hematoma and loss of gray-white matter differentiation. The hematoma was evacuated and a diagnosis of hemodialysis disequilibrium syndrome was made. Continuous hemodialysis and hyperosmolar therapy were instituted without any improvement. The CT scans were then reinterpreted as showing sagging of the brain, and the patient was placed in the Trendelenburg position which resulted in prompt improvement in her level of consciousness. A CT myelogram demonstrated an upper thoracic CSF leak that eventually required surgical correction. The patient made a complete neurological recovery. Neurological deterioration after craniotomy may be caused by brain sagging caused by a spontaneous spinal CSF leak, similar to intracranial hypotension due to intraoperative lumbar CSF drainage.

Interventional MR imaging with an endospinal imaging coil: preliminary results with anatomic imaging of the canine and cadaver spinal cord.

Percutaneous intraspinal navigation (PIN) is a new minimally invasive approach to the subarachnoid space. Using conventional radiographic fluoroscopy, entrance is gained to the lumbar subarachnoid space, allowing navigation throughout the spinal canal. Using an antenna/guidewire introduced via PIN, we performed endospinal MR imaging of the thoracic spinal cord in a cadaver and canine subject. Comparison images were obtained with an optimal surface coil. PIN allows endospinal MR imaging of the spinal cord, providing significant signal-to-noise ratio gains over conventional imaging.

Stent-coil treatment of a distal internal carotid artery dissecting pseudoaneurysm on a redundant loop by use of a flexible, dedicated nitinol intracranial stent.

Treatment of dissecting pseudoaneurysms of the distal cervical internal carotid artery with preservation of the parent artery by using stents or coils has become routine. Tortuosity remains a significant obstacle to successful endovascular treatment in some cases. We report the use of a stent-coil technique to treat a nonhealing dissecting pseudoaneurysm and associated stenosis with anatomic preservation of a redundant loop involving the stented arterial segment. This was accomplished by using a Neuroform dedicated intracranial stent.

MR-guided catheter navigation of the intracranial subarachnoid space.

Percutaneous intraspinal navigation (PIN) is a new minimally invasive approach to the CNS. The authors studied the utility of MR-guided intracranial navigation following access to the subarachnoid compartment via PIN. The passive tracking technique was employed to visualize devices during intracranial navigation. Under steady-state free precession (SSFP) MR-guidance a microcatheter-microguidewire was successfully navigated to multiple brain foci in two cadavers. SSFP MR fluoroscopy possesses adequate contrast and temporal resolution to allow MR-guided intracranial navigation.

Experimental third ventriculostomy performed using endovascular surgical techniques and their adaptation to percutaneous intradural neuronavigation: proof of concept cadaver study.

OBJECTIVE: Endoscopic third ventriculostomy has developed into a therapeutic alternative to shunting for the management of carefully selected patients with primarily noncommunicating hydrocephalus. This procedure, however, requires a general anesthetic and necessitates violation of the brain parenchyma and manipulation near vital neural structures to access the floor of the third ventricle. Using two cadavers and off-the-shelf angiographic catheters, we sought to determine whether it was possible to navigate a catheter, angioplasty balloon, and stent percutaneously through the subarachnoid space from the thecal sac into the third ventricle so as to perform a third ventriculostomy from below. METHODS: Using biplane angiography and off-the-shelf angiographic catheters along with angioplasty balloons and stents, we were able to pass a stent coaxially from the thecal sac to and across the floor of the third ventricle so as to achieve a third ventriculostomy from below. RESULTS: Coaxial catheter techniques allowed for the percutaneous insertion of a stent across the floor of the third ventricle. Ventriculostomy was confirmed by injecting contrast medium into the lateral ventricle and seeing it pass through the stent and into the chiasmatic cistern. CONCLUSION: We describe the performance of third ventriculostomies in two cadavers by use of the new concept of percutaneous intradural neuronavigation. This procedure may obviate the need for general anesthetic and minimize the potential for brain and vascular injury, especially if ultimately combined with magnetic resonance fluoroscopy.

Complications of preoperative embolization of cerebral arteriovenous malformations.

OBJECT: Preoperative embolization is viewed by the authors as a useful adjunct in the surgical management of cerebral arteriovenous malformations (AVMs). This study was performed to determine the rate of significant complication in patients undergoing this procedure. METHODS: Demographic, anatomical, and procedure data were collected prospectively. The treating physician reported complications. In addition, a review of medical records including procedure reports, operative reports, and discharge summaries was performed. Univariate statistical analysis was performed to determine if any of the variables was predictive of a poor outcome of embolization (death or permanent neurological deficit). Endovascular procedures for embolization were performed 339 times in 201 patients during an 11-year period. Female patients comprised 53.7% of the study group and 85.6% of the AVMs were supratentorial. Embolization was performed using polyvinyl alcohol particles, N-butyl cyanoacrylate, detachable coils, and/or the liquid polymer Onyx. Analyzed by procedure, a poor result of embolization occurred in 7.7%. Analyzed by patient, 11% died or had a permanent neurological deficit as a result of the embolization. None of the demographic, anatomical, or procedure variables identified were predictive of a poor outcome. CONCLUSIONS: Preoperative embolization may gradually reduce flow to an AVM, reduce intraoperative blood loss, and reduce operative time. The risks of this procedure, however, are not insignificant and must be considered in planning treatment for patients with AVMs.