Alexander G. Khandji

Urgent endovascular revascularization for symptomatic intracranial atherosclerotic stenosis

Background: Endovascular revascularization for intracranial atherosclerotic stenoses is being increasingly performed at major medical centers and has been reported to be technically feasible and safe. The authors report their experience with patients who underwent such a procedure for impending stroke and neurologic instability. Method: All 18 patients (21 intracranial lesions) treated between 1997 and 2002 at the authors’ institution with endovascular revascularization were retrospectively reviewed. Each patient had failed maximal medical therapy and was thought to be at high risk for an imminent stroke. Results: Endovascular revascularization was performed on eight distal internal carotid artery lesions, six middle cerebral artery lesions, four intracranial vertebral artery lesions, and three basilar artery lesions. Recanalization was complete in 5 arteries (Thrombolysis in Myocardial Infarction [TIMI] Grade III), partial in 14 arteries (TIMI Grade II), and complete occlusion (TIMI 0) developed in 1 artery. In a patient with a tight basilar stenosis, no angioplasty could be performed because of the inability to cross the stenosis with the guidewire. Major periprocedural complications occurred in 9 (50%) patients: intracranial hemorrhage in 3 (17%), disabling ischemic stroke in 2 (11%), and major extracranial hemorrhage in 4 (22%). Three patients died: one from intracerebral hemorrhage and two from cardiorespiratory failure. Conclusions: Endovascular revascularization of intracranial vessels is technically feasible and may be performed successfully. However, periprocedural complication and fatality rates in neurologically unstable patients are high. The results suggest that patient selection, procedure timing, and periprocedural medical management are critical factors to reduce periprocedural morbidity and mortality.

Reversible leukoencephalopathy associated with cerebral amyloid angiopathy.

The authors describe three patients with reversible leukoencephalopathy associated with cerebral amyloid angiopathy (CAA). Rapid progression of neurologic symptoms was followed by dramatic clinical and radiographic improvement. Pathologically, CAA was associated with varying degrees of inflammation ranging from none to transmural granulomatous infiltration. In the appropriate clinical context, the MRI finding of lobar white matter edema with evidence of prior hemosiderin deposition may indicate the presence of a reversible CAA leukoencephalopathy.

A Modified Transorbital Baboon Model of Reperfused Stroke

Background and Purpose Although pathophysiological studies of focal cerebral ischemia in nonhuman primates can provide important information not obtainable in rodent models, primate experimentation is limited by considerations of cost, availability, effort, and ethics. A reproducible and quantitative model that minimizes the number of animals necessary to detect differences between treatment groups is therefore crucial. Methods Eight male baboons (weight, 22±2 kg) underwent left transorbital craniectomy followed by 1 hour of temporary ipsilateral internal carotid artery occlusion at the level of the anterior choroidal artery together with bilateral temporary occlusion of both anterior cerebral arteries (A1) proximal to the anterior communicating artery. A tightly controlled nitrous oxide–narcotic anesthetic allowed for intraoperative motor evoked potential confirmation of middle cerebral artery (MCA) territory ischemia. Animals survived to 72 hours or 10 days if successfully self-caring. Outcomes were assessed with a 100-point neurological grading system, and infarct volume was quantified by planimetric analysis of both MRI and triphenyltetrazolium chloride–stained sections. Results Infarction volumes (on T2-weighted images) were 32±7% (mean±SEM) of the ipsilateral hemisphere, and neurological scores averaged 29±9. All animals demonstrated evidence of hemispheric infarction, with damage evident in both cortical and subcortical regions in the MCA vascular territory. Histologically determined infarction volumes differed by <3% and correlated with absolute neurological scores (r =0.9, P =0.003). Conclusions Transorbital temporary occlusion of the entire anterior cerebral circulation with strict control of physiological parameters can reliably produce reperfused MCA territory infarction. The magnitude of the resultant infarct with little interanimal variability diminishes the potential number of animals required to distinguish between 2 treatment regimens. The anatomic distribution of the infarct and associated functional deficits offer comparability to human hemispheric strokes.

Intrathecal Injections in Children With Spinal Muscular Atrophy Nusinersen Clinical Trial Experience

Nusinersen (ISIS-SMNRx or ISIS 396443) is an antisense oligonucleotide drug administered intrathecally to treat spinal muscular atrophy. We summarize lumbar puncture experience in children with spinal muscular atrophy during a phase 1 open-label study of nusinersen and its extension. During the studies, 73 lumbar punctures were performed in 28 patients 2 to 14 years of age with type 2/3 spinal muscular atrophy. No complications occurred in 50 (68%) lumbar punctures; in 23 (32%) procedures, adverse events were attributed to lumbar puncture. Most common adverse events were headache (n = 9), back pain (n = 9), and post–lumbar puncture syndrome (n = 8). In a subgroup analysis, adverse events were more frequent in older children, children with type 3 spinal muscular atrophy, and with a 21- or 22-gauge needle compared to a 24-gauge needle or smaller. Lumbar punctures were successfully performed in children with spinal muscular atrophy; lumbar puncture–related adverse event frequency was similar to that previously reported in children.

Cabergoline therapy of growth hormone & growth hormone/prolactin secreting pituitary tumors.

Dopamine agonists have been used as adjunctive therapy for acromegaly for many years, but relatively few studies have assessed the efficacy of a newer agonist, cabergoline. Some data suggest that cabergoline may be more effective than bromocriptine, in particular for those patients whose tumors secrete both growth hormone and prolactin. In order to assess this possibility further, we have evaluated the biochemical response to cabergoline therapy in patients with acromegaly at our center.We describe first an unusual patient who presented with a pituitary macroadenoma secreting both GH and prolactin. At presentation he had elevated levels of growth hormone 6.0 μg/L, IGF-I, 722 ng/ml, and prolactin, 6000 ng/ml. Cabergoline therapy alone was highly effective in this patient and normalized his levels of all three hormones and his gonadal function as well as produced significant shrinkage of his pituitary tumor.Fourteen other patients with more typical, active postoperative acromegaly were administered cabergoline in a 6-month, open label, dose-escalation study. Mean baseline GH was 1.3 ± .23 ng/ml and fell to a nadir of 0.85 ± .18 ng/ml on cabergoline therapy (p = 0.03). Mean baseline IGF-I was 520 ± 45.2 ng/ml and fell to a mean nadir during cabergoline therapy of 368 ± 29.8 ng/ml (p = 0.0013). At the completion of the cabergoline therapy study period, however, mean IGF-I was 453 ± 46 ng/ml, not significantly lower than the baseline value (p = 0.11). No changes in tumor sizes occurred on cabergoline therapy.Eight of 14 patients achieved a normal IGF-I at some point during the 24 weeks study period, but the efficacy of cabergoline waned with time as only 3 of 14 (21%) of patients had a persistently normal IGF-I with up to 18 months of cabergoline therapy. Six patients had modest hyperprolactinemia at diagnosis (26–142 ng/ml) and 5 patients had positive immunohistochemical staining of their tumor for prolactin, but in neither of these small groups was cabergoline therapy more effective at normalizing IGF-I than in those patients with apparently pure GH secreting tumors. Three of 14 patients (21%) had side effects that limited therapy.A trial of cabergoline as adjunctive therapy may be considered in select patients with mild disease and small tumor residuals, but the expectation for biochemical control in these patients needs to be kept low, even for tumors that co-secrete GH and prolactin.

Multiple Adjacent Vertebral Fractures After Kyphoplasty in a Patient With Steroid-Induced Osteoporosis

IN JUNE 2003, a 50-year-old white woman who was 6 months postmenopausal and had a 19-year history of systemic lupus erythematosus treated chronically with prednisone sought a second opinion for back pain at the Columbia Presbyterian Medical Center. Her pain had begun acutely in December 2002 while shoveling snow. Although a DXA in October 2001 had revealed osteopenia (L-spine T-score 1.99, total hip T-score 1.65), she had previously been free of back pain or fractures. Intranasal calcitonin was prescribed by her primary care physician for presumptive fracture-associated pain in early January 2003, but her pain persisted, prompting an MRI in March 2003 that revealed a subacute partial compression fracture of the L2 vertebral body involving the superior endplate (Fig. 1A); no other fractures were identified (T11 was not fully visualized on this image because it was primarily a lumbar spine MRI; therefore, a minor T11 fracture cannot be definitively excluded). Her orthopedist recommended kyphoplasty of L2, which was performed in April 2003. Fluoroscopy during the procedure identified the single L2 fracture, which was reduced using a Kyphon balloon and injected with 3 ml of bone cement. The patient tolerated the procedure well and was discharged the following day with dramatic pain improvement. Forty-eight hours later, however, without any increase in activity level, her low back pain recurred and became incapacitating, confining her to bed. Six days later, an MRI was performed to assess the recurrence of severe pain and revealed stable kyphoplasty changes within L2 and interval development of several new vertebral fractures, including two acute, severe compression fractures of T11 and T12, with marked anterior wedging (although T11 was not fully visualized on the initial MRI, the follow-up clearly shows a dramatic change), as well as fractures of the L1 inferior endplate, L3 and L4 superior endplates, and the L5 inferior endplate (Fig. 1B). Calcitonin was discontinued and teriparatide was started in May 2003, with a significant reduction in pain over the next month. When we first evaluated her in June 2003, examination revealed a Cushingoid-appearing woman with mild kyphosis and some tenderness to palpation in both the lower thoracic and lumbar spine. Renal, hepatic, hematopoietic, and thyroid function tests, as well as serum calcium, parathyroid hormone (PTH), N-telopeptide, and vitamin D levels, were within normal limits. Bone-specific alkaline phosphatase was elevated at 37.8 g/liter (normal, 6.4–24.4 g/liter), consistent with a healing fracture or possibly early teriparatide effect. The erythrocyte sedimentation rate (ESR) was 4 mm/h. DXA indicated L3 and total hip T-scores of 2.88 and 1.56, respectively. The temporal relationship between the kyphoplasty procedure that eliminated her pain and the subsequent recurrence of pain with documented fractures of six adjacent vertebrae on the follow-up MRI is highly suggestive of causality. It seems unlikely that manipulation during the surgical procedure itself produced these fractures or that these new fractures occurred spontaneously some time after the March MRI and before the April kyphoplasty; the patient’s pain disappeared immediately after the single L2 kyphoplasty, and the postprocedure fluoroscopy revealed no acute fractures. Although new endplate fractures might be undetected by fluoroscopy, the marked changes at T11 and T12 would be difficult to miss. Traditionally, acute vertebral fracture has been medically managed, but percutaneous vertebroplasty and kyphoplasty are becoming increasingly frequent treatments. Percutaneous vertebroplasty refers to the injection of bone cement into a fractured vertebra using fluoroscopic guidance, with the goal of providing pain relief. Kyphoplasty includes inflation of a bone tamp within the vertebral body before cement injection, thereby slightly re-expanding the fractured vertebrae. Kyphoplasty offers the potential advantage of low pressure cement injection and fewer cement leaks, as well as improvement in vertebral height deformity and kyphosis. Despite the increasing popularity of these two procedures, there have been no randomized controlled trials completed to evaluate the efficacy or safety of either procedure. Although prospective kyphoplasty case series suggest a rapid and lasting reduction in pain postprocedure, control groups are lacking. In the only nonrandomized, controlled study of either procedure, there was no significant difference in pain scores between vertebroplasty Dr Siris served as a consultant for Eli Lilly and Company, Merck & Co., Inc., Novartis, and Procter & Gamble. All other authors have no conflict of interest.

Gadolinium‐MRI in acute transverse myelopathy

A patient with acute transverse myelopathy (ATM) had serial magnetic resonance imaging (MRI) studies before and after administration of gadolinium (Gd-DTPA). Gd-DTPA-MRI was useful in estimating the pathologic extent and residual deficit expected in ATM.

Olfactory ensheathing glia injections in Beijing: misleading patients with ALS.

Different forms of cell transplantation therapy are being tested in models of ALS. While the approach offers hope to patients with ALS, much still needs to be learned in the laboratory before it is ready for human trials. Nevertheless, clinics across the world offer various types of open label cell transplantation therapy for high fees. We report a woman who received an injection into each frontal lobe in Beijing, China. Her ALS progressed at a more rapid rate after the procedure and she suffered disabling side‐effects. Clinics that give experimental and potentially harmful treatments outside the construct of well‐designed clinical trials put patients at risk and do a disservice to the ALS community.

Intramedullary inclusion cysts of the cervicothoracic junction. Report of two cases in adults and review of the literature.

Intramedullary inclusion cysts are extremely rare within the rostral spinal cord. In this case report the authors outline the clinical features and surgical treatment of one dermoid cyst and one epidermoid cyst of the cervicothoracic junction. The authors also include a relevant literature discussion regarding the treatment and the embryological origin of these lesions.

Management of residual dysplastic vessels after cerebral arteriovenous malformation resection: implications for postoperative angiography.

OBJECTIVE The verification of surgical resection of cerebral arteriovenous malformations (AVMs) relies on angiography. Abnormal vasculature often is identified after removal of the AVM. Differentiation of dysplastic feeding vessels that resemble the neovascularity of moyamoya disease, as distinct from residual AVM, is crucial for preserving critical brain areas. We review a large experience with immediate postoperative angiography after AVM resection and discuss the implications for management of abnormal dysplastic vessels discovered after AVM resection. METHODS Beginning in 1992, 86 consecutive patients with AVMs underwent operations by standard protocol for immediate postoperative angiography under the same general anesthetic. Angiographic interpretation dictated admission to the intensive care unit or return to the operating room for further resection. RESULTS In 78 patients, the angiogram revealed complete resection. Two patients were returned to the operating room, one for residual malformation with an early draining vein, and one for resection of residual dysplastic vessels. There was one postoperative hemorrhage in a patient whose postoperative angiogram was falsely negative for AVM. Six patients with residual dysplastic vessels mimicking residual AVM, but without an early draining vein, were managed conservatively. Delayed follow-up angiography demonstrated spontaneous involution of these abnormal vessels in all of these patients. CONCLUSION Residual dysplastic feeding vessels resembling the neovascularity of moyamoya disease but not associated with an early draining vein do not necessarily represent residual malformation after AVM resection. The abnormal vessels will proceed to complete spontaneous resolution. Given the difficulty of interpreting intraoperative angiography, immediate postoperative angiography may be a viable alternative after AVM resection.