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Gary B. Rajah and Yuchuan Ding

Acute ischemic stroke (AIS) is a leading cause of disability and death worldwide. To date, intravenous tissue plasminogen activator and mechanical thrombectomy have been standards of care for AIS. There have been many advances in diagnostic imaging and endovascular devices for AIS; however, most neuroprotective therapies seem to remain largely in the preclinical phase. While many neuroprotective therapies have been identified in experimental models, none are currently used routinely to treat stroke patients. This review seeks to summarize clinical studies pertaining to neuroprotection, as well as the different preclinical neuroprotective therapies, their presumed mechanisms of action, and their future applications in stroke patients.

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Gary Rajah, Sandra Narayanan and Leonardo Rangel-Castilla

Flow diversion has become a well-accepted option for the treatment of cerebral aneurysms. Given the significant treatment effect of flow diverters, numerous options have emerged since the initial Pipeline embolization device studies. In this review, the authors describe the available flow diverters, both endoluminal and intrasaccular, addressing nuances of device design and function and presenting data on complications and outcomes, where available. They also discuss possible future directions of flow diversion.

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Gary Rajah, Hamidreza Saber, Rasanjeet Singh and Leonardo Rangel-Castilla

Neuromodulation and deep brain stimulation (DBS) have been increasingly used in many neurological ailments, including essential tremor, Parkinson’s disease, epilepsy, and more. Yet for many patients and practitioners the desire to utilize these therapies is met with caution, given the need for craniotomy, lead insertion through brain parenchyma, and, at many times, bilateral invasive procedures. Currently endovascular therapy is a standard of care for emergency thrombectomy, aneurysm treatment, and other vascular malformation/occlusive disease of the cerebrum. Endovascular techniques and delivery catheters have advanced greatly in both their ability to safely reach remote brain locations and deliver devices. In this review the authors discuss minimally invasive endovascular delivery of devices and neural stimulating and recording from cortical and DBS targets via the neurovascular network.

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Matthew Schreckinger, Todd Francis, Gary Rajah, Jay Jagannathan, Murali Guthikonda and Sandeep Mittal

Lymphocytic hypophysitis is an uncommon autoimmune condition that often results in significant morbidity. Although most cases resolve spontaneously or after a short course of steroids, rarely, refractory cases can cause persistent neurological deficits despite aggressive medical and surgical management.

A 41-year-old woman presented with progressive visual loss in the left eye and was found to have a sellar mass. She underwent transsphenoidal surgery because of lesion enlargement. Histopathology was consistent with adenohypophysitis with B-cell predominance. Despite steroid treatment, her neurological condition worsened and she experienced loss of vision in the right eye. Craniotomy with decompression of the right optic nerve was performed. Her condition improved initially, but she continued to have progressive visual compromise over the following months. She was therefore treated with rituximab, a monoclonal antibody against B cells. Her vision improved significantly within a few weeks. There was no clinical or radiographic exacerbation 2 years after starting immunotherapy.

Rituximab, an anti-CD20 antibody that specifically depletes B lymphocytes, can be an effective treatment strategy for patients with steroid-refractory, B cell–predominant lymphocytic hypophysitis.

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Gary Rajah, David Altshuler, Omar Sadiq, V. Kwasi Nyame, Hazem Eltahawy and Nicholas Szerlip

OBJECT

Pathological compression fractures in cancer patients cause significant pain and disability. Spinal metastases affect quality of life near the end of life and may require multiple procedures, including medical palliative care and open surgical decompression and fixation. An increasingly popular minimally invasive technique to treat metastatic instabilities is kyphoplasty. Even though it may alleviate pain due to pathological fractures, it may fail. However, delayed kyphoplasty failures with retropulsed cement and neural element compression have not been well reported. Such failures necessitate open surgical decompression and stabilization, and cement inserted during the kyphoplasty complicates salvage surgeries in patients with a disease-burdened spine. The authors sought to examine the incidence of delayed failure of structural kyphoplasty in a series of cement augmentations for pathological compression fractures. The goal was to identify risk predictors by analyzing patient and disease characteristics to reduce kyphoplasty failure and to prevent excessive surgical procedures at the end of life.

METHODS

The authors retrospectively reviewed the records of all patients with metastatic cancer from 2010 to 2013 who had undergone a procedure involving cement augmentation for a pathological compression fracture at their institution. The authors examined the characteristics of the patients, diseases, and radiographic fractures.

RESULTS

In total, 37 patients underwent cement augmentation in 75 spinal levels during 45 surgeries. Four patients had delayed structural kyphoplasty failure necessitating surgical decompression and fusion. The mean time to kyphoplasty failure was 2.88 ± 1.24 months. The mean loss of vertebral body height was 16% in the patients in whom kyphoplasty failed and 32% in patients in whom kyphoplasty did not fail. No posterior intraoperative cement extravasation was observed in the patients in whom kyphoplasty had failed. The mean spinal instability neoplastic score was 10.8 in the patients in whom kyphoplasty failed and 10.1 in those in whom kyphoplasty did not fail. Approximately 50% of the kyphoplasty failures occurred at junctional spinal levels. All the patients in whom kyphoplasty failed had fractures in 3 or more cortical walls before treatment, whereas 46% of patients in the nonfailure group had fractures with breaching of 3 or more walls.

CONCLUSIONS

Although rare, delayed failures of structural augmentation with cement during kyphoplasty do occur and can lead to additional surgeries. A possible predictive index may include wall integrity of the vertebral body, competency of the posterior tension band, and location of the kyphoplasty at a junctional spinal level. Additional studies are required to confirm these findings.

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Gary Rajah, Chiu Yuen To, Sandeep Sood, Steven Ham, Deniz Altinok, Janet Poulik and Abilash Haridas

Blue rubber bleb nevus syndrome (BRBNS) can present with vascular malformations throughout the body, especially in the gastrointestinal tract. Spinal cord compression from these lesions is rare, particularly in the pediatric population. The authors report a case of BRBNS involving an 18-year-old female patient who presented with back pain and an epidural thoracic mass with cord compression. She underwent an uncomplicated thoracic laminectomy and decompression, with removal of what appeared to be a venous malformation. Postoperatively her pain improved, and imaging revealed resolution of cord compression. Pathological analysis highlighted dilated venous channels with myxoid degeneration in the wall with clot, characteristic of BRBNS. The early age of presentation and location are unique based on the literature search of BRBNS. The present report highlights the multiplicity of venous malformations in BRBNS, and the management of this case.

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Bradley Kolb, Hassan Fadel, Gary Rajah, Hamidreza Saber, Ali Luqman and Leonardo Rangel-Castilla

OBJECTIVE

Steno-occlusive diseases of the cerebral vasculature have been associated with cognitive decline. The authors performed a systematic review of the existing literature on intracranial steno-occlusive disease, including intracranial atherosclerosis and moyamoya disease (MMD), to determine the extent and quality of evidence for the effect of revascularization on cognitive performance.

METHODS

A systematic search of PubMed/MEDLINE, the Thomson Reuters Web of Science Core Collection, and the KCI Korean Journal Database was performed to identify randomized controlled trials (RCTs) in the English-language literature and observational studies that compared cognitive outcomes before and after revascularization in patients with steno-occlusive disease of the intracranial vasculature, from which data were extracted and analyzed.

RESULTS

Nine papers were included, consisting of 2 RCTs and 7 observational cohort studies. Results from 2 randomized trials including 142 patients with symptomatic intracranial atherosclerotic steno-occlusion found no additional benefit to revascularization when added to maximal medical therapy. The certainty in the results of these trials was limited by concerns for bias and indirectness. Results from 7 observational trials including 282 patients found some cognitive benefit for revascularization for symptomatic atherosclerotic steno-occlusion and for steno-occlusion related to MMD in children. The certainty of these conclusions was low to very low, due to both inherent limitations in observational studies for inferring causality and concerns for added risk of bias and indirectness in some studies.

CONCLUSIONS

The effects of revascularization on cognitive performance in intracranial steno-occlusive disease remain uncertain due to limitations in existing studies. More well-designed randomized trials and observational studies are needed to determine if revascularization can arrest or reverse cognitive decline in these patients.

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Cuiping Xu, Tao Yu, Guojun Zhang, Gary B. Rajah, Yuping Wang and Yongjie Li

OBJECTIVE

The aim of this study was to evaluate the electro-clinical features, etiology, treatment, and postsurgical seizure outcomes in patients with intractable epileptic spasms (ESs).

METHODS

The authors retrospectively studied the medical records of all patients who had presented with medically intractable ESs and had undergone surgery in the period between October 2009 and August 2015. The interictal electroencephalography (EEG) pattern, MRI studies, magnetoencephalography findings, and postsurgical seizure outcomes were compared.

RESULTS

Twenty-six patients, 12 boys and 14 girls (age range 3–22 years), were eligible for study inclusion. Of these 26 patients, 84.6% (22) presented with multiple seizure types including partial seizures (PSs) independent of the ESs (30.8%); ESs followed by tonic seizures (30.8%); myoclonic seizures (19.2%); tonic seizures (19.2%); ESs followed by PSs (19.2%); focal seizures with secondary generalization (15.4%); atypical absence (11.5%); PSs followed by ESs (7.7%); and myoclonic followed by tonic seizures (7.7%). Seventeen patients underwent multilobar resection and 9 underwent unilobar resection. At the last follow-up (mean 36.6 months), 42.3% of patients were seizure free (outcome classification [OC] 1), 23.1% had > 50% reduction in seizure frequency (OC2–OC4), and 34.6% had < 50% reduction in seizure frequency or no improvement (OC5 and OC6). Predictors of favorable outcomes included an interictal focal EEG pattern and concordance between interictal EEG and MRI-demonstrated lesions (p = 0.001 and 0.004, respectively).

CONCLUSIONS

A favorable surgical outcome is achievable in a highly select group of patients with ESs secondary to structural lesions. Interictal EEG can help in identifying patients with the potential for favorable resective outcomes.

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Leonardo Rangel-Castilla, Gary B. Rajah, Hakeem J. Shakir, Hussain Shallwani, Sirin Gandhi, Jason M. Davies, Kenneth V. Snyder, Elad I. Levy and Adnan H. Siddiqui

OBJECTIVE

Acute tandem occlusions of the cervical internal carotid artery and an intracranial large vessel present treatment challenges. Controversy exists regarding which lesion should be addressed first. The authors sought to evaluate the endovascular approach for revascularization of these lesions at Gates Vascular Institute.

METHODS

The authors performed a retrospective review of a prospectively maintained, single-institution database. They analyzed demographic, procedural, radiological, and clinical outcome data for patients who underwent endovascular treatment for tandem occlusions. A modified Rankin Scale (mRS) score ≤ 2 was defined as a favorable clinical outcome.

RESULTS

Forty-five patients were identified for inclusion in the study. The average age of these patients was 64 years; the mean National Institutes of Health Stroke Scale score at presentation was 14.4. Fifteen patients received intravenous thrombolysis before undergoing endovascular treatment. Thirty-seven (82%) of the 45 proximal cervical internal carotid artery occlusions were atherothrombotic in nature. Thirty-eight patients underwent a proximal-to-distal approach with carotid artery stenting first, followed by intracranial thrombectomy, whereas 7 patients underwent a distal-to-proximal approach (that is, intracranial thrombectomy was performed first). Thirty-seven (82%) procedures were completed with local anesthesia. For intracranial thrombectomy procedures, aspiration alone was used in 15 cases, stent retrieval alone was used in 5, and a combination of aspiration and stent-retriever thrombectomy was used in the remaining 25. The average time to revascularization was 81 minutes. Successful recanalization (thrombolysis in cerebral infarction Grade 2b/3) was achieved in 39 (87%) patients. Mean National Institutes of Health Stroke Scale scores were 9.3 immediately postprocedure (p < 0.05) (n = 31), 5.1 at discharge (p < 0.05) (n = 31), and 3.6 at 3 months (p < 0.05) (n = 30). There were 5 in-hospital deaths (11%); and 2 patients (4.4%) had symptomatic intracranial hemorrhage within 24 hours postprocedure. Favorable outcomes (mRS score ≤ 2) were achieved at 3 months in 22 (73.3%) of 30 patients available for follow-up, with an mRS score of 3 for 7 of 30 (23%) patients.

CONCLUSIONS

Tandem occlusions present treatment challenges, but high recanalization rates were possible in the present series using acute carotid artery stenting and mechanical thrombectomy concurrently. Proximal-to-distal and aspiration approaches were most commonly used because they were safe, efficacious, and feasible. Further study in the setting of a randomized controlled trial is needed to determine the best sequence for the treatment approach and the best technology for tandem occlusion.

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Feng Yan, Gary Rajah, Yuchuan Ding, Yang Hua, Hongqi Zhang, Liqun Jiao, Guilin Li, Ming Ren, Ran Meng, Feng Lin and Xunming Ji

OBJECTIVE

Symptomatic intracranial hypertension can be caused by cerebral venous sinus stenosis (CVSS) and cerebral venous sinus thrombotic (CVST) stenosis, which is usually found in some patients with idiopathic intracranial hypertension (IIH). Recently, at the authors’ center, they utilized intravascular ultrasound (IVUS) as an adjunct to conventional venoplasty or stenting to facilitate diagnosis and accurate stent placement in CVSS.

METHODS

The authors designed a retrospective review of their prospective database of patients who underwent IVUS-guided venous sinus stenting between April 2016 and February 2017. Clinical, radiological, and ophthalmological information was recorded and analyzed. IVUS was performed in 12 patients with IIH (9 with nonthrombotic CVSS, 3 with secondary stenosis combined with CVST) during venoplasty through venous access. The IVUS catheter was used from a proximal location to the site of stenosis. Post-stenting follow-up, including symptomatic improvement, stent patency, and adjacent-site stenosis, was assessed at 1 year.

RESULTS

Thirteen stenotic cerebral sinuses in 12 patients were corrected using IVUS-guided stenting. No technical or neurological complications were encountered. The IVUS images were excellent for the diagnosis of the stenosis, and intraluminal thrombi were clearly visualized by using IVUS in 3 (25%) of the 12 patients. A giant arachnoid granulation was demonstrated in 1 (8.3%) of the 12 patients. Intravenous compartments or septations (2 of 12, 16.7%) and vessel wall thickening (6 of 12, 50%) were also noted. At 1-year follow-up, 10 of 12 patients were clinically symptom-free in our series.

CONCLUSIONS

IVUS is a promising tool with the potential to improve the diagnostic accuracy in IIH, aiding in identification of the types of intracranial venous stenosis, assisting in stent selection, and guiding stent placement. Further study of the utility of IVUS in venous stenting and venous stenosis pathology is warranted.