Gordon Sze

The potential for vigabatrin-induced intramyelinic edema in humans.

Summary: Purpose: Vigabatrin (Sabril, Hoechst Marion Roussel) is an antiepilepsy drug (AED) presently marketed in 64 countries for the treatment of partial and secondarily generalized seizures. Vigabatrin (VGB) is marketed in a subset of these countries for the treatment of infantile spasms. Clinical experience in humans has shown that VGB provides effective seizure control with a wide margin of safety. However, animal toxicity studies raised concern when prolonged administration of VGB was shown to induce intramyelinic edema (IME) in some laboratory animal species.

Safety and efficacy of intravenous glyburide on brain swelling after large hemispheric infarction (GAMES-RP): a randomised, double-blind, placebo-controlled phase 2 trial.

BACKGROUND Preclinical models of stroke have shown that intravenous glyburide reduces brain swelling and improves survival. We assessed whether intravenous glyburide (RP-1127; glibenclamide) would safely reduce brain swelling, decrease the need for decompressive craniectomy, and improve clinical outcomes in patients presenting with a large hemispheric infarction. METHODS For this double-blind, randomised, placebo-controlled phase 2 trial, we enrolled patients (aged 18-80 years) with a clinical diagnosis of large anterior circulation hemispheric infarction for less than 10 h and baseline diffusion-weighted MRI image lesion volume of 82-300 cm(3) on MRI at 18 hospitals in the USA. We used web-based randomisation (1:1) to allocate patients to the placebo or intravenous glyburide group. Intravenous glyburide was given as a 0·13 mg bolus intravenous injection for the first 2 min, followed by an infusion of 0·16 mg/h for the first 6 h and then 0·11 mg/h for the remaining 66 h. The primary efficacy outcome was the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-4 at 90 days without undergoing decompressive craniectomy. Analysis was by per protocol. Safety analysis included all randomly assigned patients who received the study drug. This trial is registered with ClinicalTrials.gov, number NCT01794182. FINDINGS Between May 3, 2013, and April 30, 2015, 86 patients were randomly assigned but enrolment was stopped because of funding reasons. The funder, principal investigators, site investigators, patients, imaging core, and outcomes personnel were masked to treatment. The per-protocol study population was 41 participants who received intravenous glyburide and 36 participants who received placebo. 17 (41%) patients in the intravenous glyburide group and 14 (39%) in the placebo group had an mRS score of 0-4 at 90 days without decompressive craniectomy (adjusted odds ratio 0·87, 95% CI 0·32-2·32; p=0·77). Ten (23%) of 44 participants in the intravenous glyburide group and ten (26%) of 39 participants in the placebo group had cardiac events (p=0·76), and four of 20 had serious adverse events (two in the intravenous glyburide group and two in the placebo group, p=1·00). One cardiac death occurred in each group (p=1·00). INTERPRETATION Intravenous glyburide was well tolerated in patients with large hemispheric stroke at risk for cerebral oedema. There was no difference in the composite primary outcome. Further study is warranted to assess the potential clinical benefit of a reduction in swelling by intravenous glyburide. FUNDING Remedy Pharmaceuticals.

Nerve root hypertrophy as the cause of lumbar stenosis in chronic inflammatory demyelinating polyradiculoneuropathy.

Two patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) developed signs of lumbar stenosis. Radiologic, intraoperative, and pathologic findings demonstrated lumbar stenosis secondary to nerve root hypertrophy. This syndrome has been demonstrated in hereditary, but not acquired, demyelinating neuropathies. CIDP should be considered in the differential diagnosis of sciatica and nerve root hypertrophy.

Neuro-Lyme Disease: MR Imaging Findings

PURPOSE To describe the neuroimaging manifestations of Lyme disease at magnetic resonance (MR) imaging of the brain. MATERIALS AND METHODS Institutional review board approval was obtained and HIPAA compliance was followed. This study retrospectively reviewed the MR imaging findings of all patients seen from 1993 to 2007 in whom neuro-Lyme disease was suspected and who were referred for MR imaging of the brain for the evaluation of neurologic symptoms. RESULTS Of 392 patients suspected of having neuro-Lyme disease, 66 patients proved to have the disease on the basis of clinical criteria, serologic results, and response to treatment. Seven of these 66 patients showed foci of T2 prolongation in the cerebral white matter, one had an enhancing lesion with edema, and three demonstrated nerve-root or meningeal enhancement. Of the seven patients with foci of T2 prolongation in the white matter, three were an age at which white matter findings due to small-vessel disease are common. CONCLUSION In cases of nerve-root or meningeal enhancement, Lyme disease should be considered in the differential diagnosis in the proper clinical setting.

Magnetic resonance imaging in patients with central nervous system pathology: a comparison of OptiMARK (Gd-DTPA-BMEA) and Magnevist (Gd-DTPA).

RATIONALE AND OBJECTIVES The objective of the two pivotal phase 3 studies was to evaluate the safety and efficacy of OptiMARK (Gd-DTPA-bis(methoxyethylamide) [Gd-DTPA-BMEA]) compared with Magnevist (Gd-DTPA) in magnetic resonance imaging of the central nervous system. METHODS Two multicenter, randomized, double-blind, parallel group studies were conducted in 395 patients with known or suspected central nervous system pathology. Subjects were randomized to receive a single 0.1 mmol/kg intravenous injection of either Gd-DTPA-BMEA or Gd-DTPA. The safety of Gd-DTPA-BMEA and Gd-DTPA was monitored for up to 72 hours after study drug administration. Precontrast and postcontrast administration magnetic resonance scans were acquired using identical imaging planes and techniques. RESULTS No deaths or unexpected adverse events were reported in either group. A comparison of adverse events by intensity and relation demonstrated no statistically significant differences between the two groups. Gd-DTPA-BMEA and Gd-DTPA were equivalent with respect to confidence in diagnosis, conspicuity, and border delineation. CONCLUSIONS Gd-DTPA-BMEA and Gd-DTPA demonstrated comparable efficacy profiles, and the safety profiles were considered similar.

Does prenatal stress alter the developing connectome

Human neurodevelopment requires the organization of neural elements into complex structural and functional networks called the connectome. Emerging data suggest that prenatal exposure to maternal stress plays a role in the wiring, or miswiring, of the developing connectome. Stress-related symptoms are common in women during pregnancy and are risk factors for neurobehavioral disorders ranging from autism spectrum disorder, attention deficit hyperactivity disorder, and addiction, to major depression and schizophrenia. This review focuses on structural and functional connectivity imaging to assess the impact of changes in women’s stress-based physiology on the dynamic development of the human connectome in the fetal brain.

Fungal Infections of the Central Nervous System

Fungal infections of the central nervous system (CNS) frequently occur in the immunocompromised or debilitated host. Imaging findings are non-specific but may be organized into extra-axial, parenchymal, and vascular categories. Furthermore, knowledge of fungal morphology may predict the imaging manifestations with large, hyphal species having a predilection for brain parenchymal involvement, while small, unicellular organisms typically result in meningitis. Advanced imaging techniques such as diffusion-weighted imaging, MR perfusion and MR spectroscopy, when combined with clinical findings, may help in differentiating fungal disease from other mimckers such as pyogenic infection or cystic metastases.

Magnetic resonance imaging in the evaluation of spinal tumors

Magnetic resonance imaging (MRI), which has recently begun to replace myelography, postmyelography computed tomography (CT), and to some extent, bone scans, has become the procedure of choice in the evaluation of spinal tumors; the applications of MRI in this role are reviewed. In the extradural space, MRI is the most sensitive technique for the detection of tumors in the vertebral bodies. At the same time, it provides superb delineation of suspected thecal sac impingement. In the intradural extramedullary space, MRI is generally as accurate as myelography and postmyelography CT while being noninvasive. Finally, in the intramedullary space, MRI is unquestionably the procedure of choice in the evaluation of suspected cord tumors. In general, MRI has become the best initial procedure in the evaluation of suspected tumors of the spine, regardless of the space in which they may lie; frequently, it is the only required examination.

Emotional facial paresis with striatocapsular infarction

Emotional facial paresis (EFP) refers to hemifacial paresis of emotionally evoked or spontaneous smiling or weeping with preserved volitional movements of the face. The anatomical location for this phenomenon has been controversial. We report a 15-year-old boy with EFP. Follow-up MRI demonstrated infarction limited to the head of the caudate, putamen and anterior limb of the internal capsule on the contralateral side. This case lends support for selective damage at a striatal or capsular site in the production of EFP.

Lumbar disc nomenclature: version 2.0: recommendations of the combined task forces of the North American Spine Society, the American Society of Spine Radiology, and the American Society of Neuroradiology.

Study Design. This article comprises a review of the literature pertaining to the normal and pathological lumbar disc and the compilation of a standardized nomenclature. Objective. To provide a resource that promotes a clear understanding of lumbar disc terminology among clinicians, radiologists, and researchers. Summary of Background Data. The article “Nomenclature and Classification of Lumbar Disc Pathology. Recommendations of the Combined Task Forces of the North American Spine Society, American Society of Spine Radiology and American Society of Neuroradiology” was published in 2001 in Spine