Laszlo Mechtler

A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma

RMP-7, a bradykinin analog, temporarily increases the permeability of the blood-brain tumor barrier to chemotherapy drugs like carboplatin. We conducted a randomized, controlled trial of carboplatin and RMP-7 versus carboplatin and placebo in patients with recurrent malignant glioma. The primary outcome measure was time to tumor progression (TTP). Adults with recurrent glioblastoma multiforme or anaplastic glioma were randomized in a 1:1 ratio to receive carboplatin and either RMP-7 or placebo. Radiation therapy had failed in all patients, and they may have received prior chemotherapy. Carboplatin (dosed to achieve an area under the curve of 5 mg/ml x time for patients who had received prior chemotherapy, or 7 mg/ml x time for those who had not) was given intravenously every 4 weeks, followed by intravenous infusion of either RMP-7 or placebo (300 ng/kg). TTP, tumor response, neuropsychological assessments, functional independence, and quality of life assessments were analyzed every 4 weeks. There were 122 patients enrolled, 62 in the RMP-7 and carboplatin group and 60 in the placebo and carboplatin group. Median TTP was 9.7 weeks (95% CI, 8.3-12.6 weeks) for the RMP-7 and carboplatin group and 8.0 weeks (95% CI, 7.4-12.6 weeks) for the placebo and carboplatin group. Median survival times were 26.9 weeks (95% CI, 21.3-37.6 weeks) for the RMP-7 group and 19.9 weeks (95% CI, 15.0-31.3 weeks) for the placebo group. No differences were noted for time to worsening of neuropsychological assessments, functional independence, or quality of life assessments. The use of RMP-7 had no effect on the pharmacokinetics or toxicity of carboplatin. At the dose and schedule used in this trial, RMP-7 did not improve the efficacy of carboplatin. Recent preclinical pharmacokinetic modeling of RMP-7 suggests that higher doses of RMP-7 may be required to increase carboplatin delivery to tumor.

Occipital Lobe Seizures as the Major Clinical Manifestation of Reversible Posterior Leukoencephalopathy Syndrome: Magnetic Resonance Imaging Findings

Summary: Purpose: Reversible posterior leukoencephalopathy syndrome (RPLS) is an increasingly recognized brain disorder most commonly associated with malignant hypertension, toxemia of pregnancy, or the use of immunosuppressive agents. When associated with acute hypertension, RPLS typically occurs concurrently with the fulminant clinical syndrome of hypertensive encephalopathy. We describe occipital lobe seizures, in the setting of only moderate elevations of blood pressure, as the major clinical manifestation of RPLS.

Role of fluorodeoxyglucose positron emission tomography in the diagnosis of neurosarcoidosis

A 45-year-old man developed seizures and myelopathy. MRI showed bitemporal and cervical spinal cord hyperintense lesions on T2-weighted and FLAIR images that contrast-enhanced. Initial evaluation for sarcoidosis was negative, including serum angiotensin converting enzyme (ACE) and chest X-ray. Whole body fluorodeoxyglucose positron emission tomography (FDG-PET) revealed multiple hypermetabolic hilar and mediastinal foci and spinal cord hypermetabolism at the site of MRI abnormality. Temporal lobe MRI lesions were hypometabolic. Mediastinal lymph node biopsy was consistent with sarcoidosis. The brain, spinal cord, and chest metabolic abnormalities together with the clinical presentation were interpreted as being most consistent with sarcoidosis. FDG-PET helped target the site of biopsy that subsequently confirmed the diagnosis histologically. In patients with perplexing neurologic presentations, whole body FDG-PET can help secure a timely and minimally invasive diagnosis of neurosarcoidosis.

MRI FINDINGS IN LUMBAR PUNCTURE HEADACHE SYNDROME: ABNORMAL DURAL-MENINGEAL AND DURAL VENOUS SINUS ENHANCEMENT

Intracranial hypotension (IH) is a treatable cause of persistent headaches. Persistent cerebrospinal fluid (CSF) leak at a lumbar puncture (LP) site may cause IH. We present postcontrast MRI of a patient with post-lumbar-puncture headache (LPHA) showing abnormal, intense, diffuse, symmetric, contiguous dural-meningeal (pachymeningeal) enhancement of the supratentorial and infratentorial intracranial dura, including convexities, interhemispheric fissure, tentorium, and falx. MRI also showed abnormal dural venous sinus enhancement, a new finding in LPHA, suggesting compensatory venous expansion. Thus, IH and venodilatation may play a role in the development of LPHA.

Spinal Cord Tumors: New Views and Future Directions

Spinal cord tumors are uncommon neoplasms that, without treatment, can cause significant neurologic morbidity and mortality. The historic classification of spine tumors is based on the use of myelography with 3 main groups: (1) extramedullary extradural, (2) intradural extramedullary, and (3) intradural intramedullary. This chapter focuses on intramedullary spinal cord tumors (ISCTs), with an emphasis on new diagnostic imaging modalities and treatment options. The common ISCTs include ependymoma, astrocytoma and hemangioblastoma, which together account for over 90% of primary ISCTs. Rare tumors such as gangliglioma, oligodendroglioma, paraganglioma, melanocytoma, lipoma, and primary spinal cord lymphoma are also included in this review, in addition to spinal cord metastatic disease.

Magnetic resonance imaging findings in acute cerebellitis

Cerebellitis, also known as acute cerebellar ataxia, is an inflammatory syndrome of cerebellar dysfunction that may reflect an infectious, post-infectious, or post-vaccination disorder. We present serial magnetic resonance imaging (MRI) findings in a partially reversible, idiopathic cerebellitis. Bilateral cerebellar parenchymal abnormalities were noted, including hyperintensities on T2-weighted images and cerebellar swelling. After contrast administration, the cerebellum showed abnormal bilateral enhancement. The authors state this represents the first report of abnormal contrast enhancement in this condition. The MRI lesions most likely reflect the reversible, inflammatory nature of the syndrome.

Cranial magnetic resonance imaging findings in bacterial endocarditis: the neuroimaging spectrum of septic brain embolization demonstrated in twelve patients.

Infective endocarditis (IE) is an elusive systemic disorder that is often associated with neurologic complications. The contribution of brain magnetic resonance imaging (MRI) to the diagnosis of IE and the spectrum of such findings has been only sparsely described previously. The authors report cranial MRI findings in 12 patients with IE. Each of the patients had MRI evidence of cerebral embolization, with multiple brain lesions noted in most patients (n = 1 0). Cortical branch infarction was the most common lesion (n = 8), which usually involved the distal middle cerebral artery tree. The next most common finding (n = 7) was numerous small embolic lesions which typically lodged in the supratentorial gray‐white junction, some of which were clinically silent and many of which enhanced (probable microabscesses). Brain hemorrhages were noted in four patients, most commonly subarachnoid hemorrhage (n = 3). Two patients developed multiple frank parenchymal macroabscesses/cerebritis lesions. A previously unreported finding in septic embolization, a stroke that became infected with abscess formation (“septic infarction”), was noted in two patients. MRI showed orbital cellulitis in two patients. Most patients studied with gadolinium showed enhancement of lesions (n = 5/8). The authors conclude that cranial MRI may be a valuable tool in the evaluation of patients with IE. The presence of characteristic cranial MRI lesions, especially of multiple types, may prompt early diagnosis and treatment. Key words: MRI, brain, endocarditis, septic emboli, abscess, stroke, orbital infection.

Cognitive impairment after acute supratentorial stroke : a 6-month follow-up clinical and computed tomographic study

SummaryTo document the occurrence, time course, and predictors of global cognitive impairment following a supratentorial stroke, we prospectively studied 41 consecutive patients with acute cerebral ischemia and no evidence of pre-existing intellectual disturbances. The Graded Neurologic Scale and Mattis Dementia Rating Scale were used to assess neurologic and cognitive deficits within the first week, 3 weeks and 6 months after the onset of symptoms. CT was performed at each examination and semiquantitative measurements of infarct volumes and brain atrophy were obtained. Sixty-one percent of patients were found to be cognitively impaired within the first week. After 6 months this deficit had resolved in 24%, but was still present in 37% of individuals. Initial findings associated with a high risk of longterm intellectual dysfunction were: 1. moderately severe cognitive impairment, 2. diminished alertness in the acute stroke stage, 3. infarction involving the temporal lobe, 4. evidence of multiple brain infarcts and 5. pronounced ventricular enlargement. Logistic regression analysis revealed temporal infarcts and evidence of multiple ischemic lesions as the most powerful predictors of persistent cognitive impairment. By these two factors alone, 85.4% of study participants could be correctly classified regarding their cognitive outcome. These results suggest cognitive dysfunction to be a frequent sequela of supratentorial stroke. Its long-term persistence may be predicted on the basis of certain features.

Neuroimaging in Neuro-Oncology

Neuroimaging is now entering a more mature era, whereby we can ask sophisticated questions concerning the biologic behavior of brain tumors. Multimodality imaging (CT, MRI, PET) offers the most precise information noninvasively on tumor type and grade, guides therapeutic choices, and assesses the effects of therapy. The incorporation of functional MRI (such as diffusion-weighted imaging, diffusion tensor imaging, proton MR spectroscopy, and perfusion-weighted imaging) has allowed neuro-oncologists a window of opportunity to assess the biologic behavior of brain neoplasms. These new multimodality approaches will be routinely used preoperatively, intraoperatively, and eventually, therapeutically.

Advanced Neuroimaging of Mild Traumatic Brain Injury

This article focuses on advancements in neuroimaging techniques, compares the advantages of each of the modalities in the evaluation of mild traumatic brain injury, and discusses their contribution to our understanding of the pathophysiology as it relates to prognosis. Advanced neuroimaging techniques discussed include anatomic/structural imaging techniques, such as diffusion tensor imaging and susceptibility-weighted imaging, and functional imaging techniques, such as functional magnetic resonance imaging, perfusion-weighted imaging, magnetic resonance spectroscopy, and positron emission tomography.