Kesav Raghavan

MKK6 binds and regulates expression of Parkinson's disease-related protein LRRK2.

J. Neurochem. (2010) 112, 1593–1604.

Low testosterone is associated with disability in men with multiple sclerosis

Background: Gonadal steroids may modulate disease course in multiple sclerosis (MS). Objective: To assess the prevalence and clinical associations of hypogonadism in men with MS. Methods: Male patients, aged 18–65 years, with relapsing–remitting MS (RRMS) or clinically-isolated syndrome (CIS) and their first symptom < 10 years prior were selected from a longitudinal clinical study. We measured their hormones in stored morning blood samples, and collected their Expanded Disability Status Scale (EDSS) scores every 6 months and their Symbol Digit Modalities Test (SDMT) results annually. Results: Our analysis included 96 men with a mean age of 40 years, EDSS of 1.1 and disease duration of 4.6 years. Of these men, 39% were hypogonadal (total testosterone < 288 ng/dL); none showed compensatory elevations in luteinizing hormone. Their low testosterone levels and testosterone:estradiol ratios were negatively correlated with body mass index (BMI) and leptin, and showed no correlation with 25-hydroxy-vitamin D levels. In our primary cross-sectional analyses, there was a negative age-adjusted correlation between total testosterone and EDSS (p = 0.044). In the age-adjusted longitudinal analyses, higher baseline testosterone levels were associated with less decline in SDMT (p = 0.012). Conclusions: Men with MS may experience hypogonadotropic hypogonadism. Low testosterone levels may be associated with worse clinical outcomes. A potential neuroprotective role for testosterone warrants further investigation.

Imaging of Cerebrovascular Disease in Pregnancy and the Puerperium

OBJECTIVE The purpose of this article is to review the unique physiologic changes that characterize pregnancy and the puerperium, some that substantially affect the cerebrovascular system. Conditions that can cause neurologic deterioration and share features with preeclampsia-eclampsia include postpartum angiopathy, reversible cerebral vasoconstriction syndrome, posterior reversible encephalopathy syndrome, and amniotic fluid embolism. Other conditions not specific to this patient group include cerebral venous thrombosis, cervicocephalic arterial dissection, ischemic stroke, and hemorrhagic stroke, which can pose specific diagnostic and therapeutic challenges. CONCLUSION Radiologists must be familiar with the imaging findings of cerebrovascular complications and pathologic entities encountered during pregnancy and the puerperium. Ongoing improvements in understanding of molecular changes during pregnancy and the puerperium and advances in diagnostic tests should allow radiologists to continue to make important contributions to the care of this patient population.

MRI of the Knee and Shoulder Performed Before Radiography

PURPOSE Available data are limited on the level of adherence to established guidelines for appropriate utilization of MR in musculoskeletal imaging. This study estimates the percentage of MRI examinations for knee and shoulder pain or tendonitis performed without prior radiography, which thus may fall outside the ACR Appropriateness Criteria for the Medicare and commercially insured populations. METHODS The percentage of MRI examinations for knee and shoulder pain or tendonitis performed without prior radiography was estimated among patients in the Medicare 5% carrier claims limited data set and among commercially insured patients in the Truven Marketscan Treatment Pathways database in 2010. RESULTS Approximately 28% of all knee MRIs, and 35%-37% of all shoulder MRIs were performed without recent prior radiographs. The extrapolated expense of these potentially unwarranted MRIs in the entire fee-for-service Medicare population was between

Progression rates and sample size estimates for PPMS based on the CLIMB study population

20 and

MDCT Diagnosis of Perineural Invasion Involving the Celiac Plexus in Intrahepatic Cholangiocarcinoma: Preliminary Observations and Clinical Implications

35 million. Between 20% and 23% of patients undergoing knee MRI, and 27%-32% undergoing shoulder MRI, did not have radiographic examination at any point before the MRI in the same calendar year. CONCLUSIONS MRI performed without prior radiography represents a potential gap in care and should be considered as an area for establishment of performance measures.

Ruptured middle cerebellar peduncle AVM presenting with a coma treated to complete recovery with endovascular and intensive care therapy: discussion of management.

Background: The clinical trial design for primary progressive multiple sclerosis (PPMS) requires understanding of disability progression in modern patient cohorts. Objective: The objective of this paper is to characterize demographic and clinical characteristics of PPMS and assess rate of disability progression. Methods: We studied PPMS (n = 73) and relapsing-onset MS (ROMS) patients (n = 1541) enrolled in CLIMB, a longitudinal study of MS patients at the Brigham and Women’s Hospital (Boston, MA). Disability progression for each group was compared using interval-censored survival analysis and time to six-month sustained progression. Results: The PP group had a 1.09:1 male:female ratio compared to 1:2.89 for the RO group and greater mean age of onset (PP: 44.4±9.6; RO: 32.7±9.9; p < 0.0001). Motor symptoms at onset and first symptoms localized to spinal cord were each strongly associated with PPMS (p < 0.001). Median time from onset to EDSS 6.0 was faster in PPMS (p < 0.001). PPMS patients progressed faster to EDSS 3 (p < 0.001) and from EDSS 3 to 6 (p < 0.001). Median time to sustained progression in the PP group was 4.85 years (95% CI 2.83–8.35), significantly faster than the RO group (p < 0.001). Conclusions: Our modern PPMS cohort is demographically similar to previously studied cohorts. PPMS is associated with faster disability accrual than ROMS. Current real-world observations of time to sustained progression will inform design of new clinical trials for PPMS.

Developing Quality Measures for Diagnostic Radiologists: Part 2

OBJECTIVE The purpose of this study was to test the hypothesis that soft-tissue infiltration along the celiac plexus and delayed enhancement exceeding two-thirds of the tumor area on preoperative MDCT correlate with histologic evidence of perineural invasion in resected intrahepatic cholangiocarcinomas. MATERIALS AND METHODS Two experienced abdominal radiologists retrospectively reviewed preoperative multiphasic MDCT scans of 20 patients who underwent resection of intrahepatic cholangiocarcinoma, identifying soft-tissue infiltration along the celiac plexus, delayed enhancement exceeding two-thirds of the tumor area, and maximum tumor diameter. Consensus findings were compared with intratumoral perineural invasion in resected intrahepatic cholangiocarcinomas using the Fisher exact test. RESULTS Six patients had histologic intratumoral perineural invasion, five of whom had soft-tissue infiltration along the celiac plexus on preoperative MDCT, with corresponding 83.3% sensitivity and 92.9% specificity for perineural invasion and significant association between these MDCT and histologic findings (p = 0.002). No patients with histologic perineural invasion had enhancement exceeding two-thirds of the tumor area on MDCT; sensitivity was 0.0% for this finding. Tumor diameter on MDCT was not significantly associated with perineural invasion at histopathology (p = 0.530). CONCLUSION Soft-tissue infiltration along the celiac plexus on MDCT is an indicator of perineural invasion in patients with intrahepatic cholangiocarcinoma. The data did not confirm an association between delayed enhancement exceeding two-thirds of the tumor area and perineural invasion. Because perineural invasion from intrahepatic cholangiocarcinoma is associated with a very poor prognosis and is generally a contraindication to surgery, the MDCT diagnosis of celiac plexus perineural invasion in patients with intrahepatic cholangiocarcinoma may have important implications for prognosis and treatment planning.

LRRK2 Modulates Vulnerability to Mitochondrial Dysfunction in Caenorhabditis elegans

Cerebellar AVMs represent 60–75% of all posterior fossa AVMs nd most commonly present with hemorrhage, with a 75–92% eported rate of hemorrhagic presentation [1]. Surgery is currently onsidered the preferred treatment for ruptured cerebellar AVMs, s it eliminates rebleed risk, and allows evacuation of hematomas hich can compress the brainstem or fourth ventricle (V4) [1]. We eport on a young patient with a ruptured cerebellar AVM and a arge hematoma who, despite presenting in a coma, made a full ecovery on non-surgical management.

Intraoperative fires during emergent colon surgery.

The ACR convened a cross-specialty, multidisciplinary technical expert panel to identify and define new measures for quality improvement. These measures can be included in the ACRs National Radiology Data Registry and potentially used in the CMS quality reporting programs. The technical expert panel was tasked with developing measures that reflect the most rigorous clinical evidence and address areas most in need of performance improvement. The measures described in these articles represent a new phase in the ACRs efforts to develop meaningful measures for radiologists that promote population health through diagnostic accuracy, clinical effectiveness, and care coordination.