Case 212: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids.

History A previously healthy 23-year-old white man presented to the emergency department of our hospital with a 2-month history of dysarthria, progressively worsening vertigo, and difficulty walking. A diagnosis of retinitis pigementosa was made in this patient's childhood. He did not have any history of congenital syphilis. He did not have a history of nausea or vomiting, fever, weight loss, headache, photophobia, seizure, extremity weakness, or sensory disturbance. Physical examination revealed dysarthria, dysmetria, and ataxia. Kernig and Brudzinski signs were absent, and pathergy test results were negative. Laboratory evaluation revealed normal complete and differential blood counts and normal serum chemistry, including a normal serum angiotensin-converting enzyme level. Analysis of his serum was negative for antinuclear antibody (or ANA), cytoplasmic antineutrophil cvtoplasmic antibody (or cANCA), Sjögren syndrome antigens A and B (SS-A and SS-B, respectively), antitissue transglutaminase and antiendomysial antibodies, and paraneoplastic profile. Serum analysis was also negative for human immunodeficiency virus type 1 and type 2 RNA, Venereal Disease Research Laboratory (VDRL) test, rapid plasma regain (RPR), and fluorescent treponemal antibody absorption. Cerebrospinal fluid (CSF) analysis revealed clear fluid, a normal glucose level (64 mg/dL [3.6 mmol/L]; normal range, 40-70 mg/dL [2.2-3.9 mmol/L]), an elevated protein level (97 mg/dL; normal range, 12-60 mg/dL), and an elevated white blood cell count (7/mm(3) [0.007 ×10(9)/L] in tube 1 and 17/mm(3) [0.017 × 10(9)/L] in tube 2) with 84% lymphocytes. CSF immunoglobulin G level was elevated (30.1 mg/dL; normal, <5.9 mg/dL); however, there were no oligoclonal bands. Gram staining, acid-fast staining, and lactic acid, cryptococcal antigen, histoplasma antigen, herpes simplex virus polymerase chain reaction, VDRL, and RPR test results for CSF were negative. CSF did not grow any bacteria, fungus, or acid-fast bacillus at culture. CSF flow cytometry did not reveal a monoclonal lymphoid population. Initial imaging included brain magnetic resonance (MR) imaging. Computed tomography (CT) images of the chest, abdomen, and pelvis were normal (not shown). The patient's clinical symptoms and imaging findings responded to treatment with a high dose of oral steroids. However, the patient's symptoms exhibited clinical and radiologic progression after several attempts to taper the steroid dose.

Survival analysis in patients with newly diagnosed primary glioblastoma multiforme using pre- and post-treatment peritumoral perfusion imaging parameters.

The objective of this study was to evaluate if peritumoral (PT) perfusion parameters obtained from dynamic susceptibility weighted contrast enhanced perfusion MRI can predict overall survival (OS) and progression free survival (PFS) in patients with newly diagnosed glioblastoma multiforme (GBM). Twenty-eight newly diagnosed GBM patients, who were treated with resection followed by concurrent chemoradiation and adjuvant chemotherapy, were included in this study. Evaluated perfusion parameters were pre- and post-treatment PT relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF). Proportional hazard analysis was used to assess the relationship OS, PFS and perfusion parameters. Kaplan-Meier survival estimates and log-rank test were used to characterize and compare the patient groups with high and low perfusion parameter values in terms of OS and PFS. Pretreatment PT rCBV and rCBF were not associated with OS and PFS whereas there was statistically significant association of both posttreatment PT rCBV and rCBF with OS and posttreatment rCBV with PFS (association of PFS and posttreatment rCBF was not statistically significant). Neither the Kaplan-Meier survival estimates nor the log-rank test demonstrated any differences in OS between high and low pretreatment PT rCBV values and rCBF values; however, high and low post-treatment PT rCBV and rCBF values did demonstrate statistically significant difference in OS and PFS. Our study found posttreatment, not pretreatment, PT perfusion parameters can be used to predict OS and PFS in patients with newly diagnosed GBM.

Tobacco smoke exposure induces nicotine dependence in rats.

RATIONALE: Tobacco smoke contains nicotine and many other compounds that act in concert on the brain reward system. Therefore, animal models are needed that allow the investigation of chronic exposure to the full spectrum of tobacco smoke constituents. OBJECTIVES: The aim of these studies was to investigate if exposure to tobacco smoke leads to nicotine dependence in rats. METHODS: The intracranial self-stimulation procedure was used to assess the negative affective aspects of nicotine withdrawal. Somatic signs were recorded from a checklist of nicotine abstinence signs. Nicotine self-administration sessions were conducted to investigate if tobacco smoke exposure affects the motivation to self-administer nicotine. Nicotinic receptor autoradiography was used to investigate if exposure to tobacco smoke affects central alpha7 nicotinic acetylcholine receptor (nAChR) and non-alpha7 nAChR levels (primarily alpha4beta2 nAChRs). RESULTS: The nAChR antagonist mecamylamine dose-dependently elevated the brain reward thresholds of the rats exposed to tobacco smoke and did not affect the brain reward thresholds of the untreated control rats. Furthermore, mecamylamine induced more somatic withdrawal signs in the smoke-exposed rats than in the control rats. Nicotine self-administration was decreased 1 day after the last tobacco smoke exposure sessions and was returned to control levels 5 days later. Tobacco smoke exposure increased the alpha7 nAChR density in the CA2/3 area and the stratum oriens and increased the non-alpha7 nAChR density in the dentate gyrus. CONCLUSION: Tobacco smoke exposure leads to nicotine dependence as indicated by precipitated affective and somatic withdrawal signs and induces an upregulation of nAChRs in the hippocampus.