Faculty Bibliography

In familial and sporadic multiple system atrophy (MSA) patients, deficiency of coenzyme Q10 (CoQ10) has been associated with mutations in COQ2, which encodes the second enzyme in the CoQ10 biosynthetic pathway. Cerebellar ataxia is the most common presentation of CoQ10 deficiency, suggesting that the cerebellum might be selectively vulnerable to low levels of CoQ10 To investigate whether CoQ10 deficiency represents a common feature in the brains of MSA patients independent of the presence of COQ2 mutations, we studied CoQ10 levels in postmortem brains of 12 MSA, 9 Parkinson disease (PD), 9 essential tremor (ET) patients, and 12 controls. We also assessed mitochondrial respiratory chain enzyme activities, oxidative stress, mitochondrial mass, and levels of enzymes involved in CoQ biosynthesis. Our studies revealed CoQ10 deficiency in MSA cerebellum, which was associated with impaired CoQ biosynthesis and increased oxidative stress in the absence of COQ2 mutations. The levels of CoQ10 in the cerebella of ET and PD patients were comparable or higher than in controls. These findings suggest that CoQ10 deficiency may contribute to the pathogenesis of MSA. Because no disease modifying therapies are currently available, increasing CoQ10 levels by supplementation or upregulation of its biosynthesis may represent a novel treatment strategy for MSA patients.

BACKGROUND AND PURPOSE: Infections are common after intracerebral hemorrhage, but little is known about the risk of serious infection requiring readmission after hospital discharge. METHODS: To determine if infections are prevalent in patients readmitted within 30 days of discharge, we performed a retrospective cohort study of patients discharged from nonfederal acute care hospitals in California with a primary diagnosis of intracerebral hemorrhage between 2006 and 2010. We excluded patients who died during the index admission, were discharged against medical advice, or were not California residents. Our main outcome was 30-day unplanned readmission with primary infection-related International Classification of Diseases, Ninth Revision, Clinical Modification code. RESULTS: There were 24 540 index intracerebral hemorrhage visits from 2006 to 2010. Unplanned readmissions occurred in 14.5% (n=3550) of index patients. Of 3550 readmissions, 777 (22%) had an infection-related primary diagnosis code. When evaluating primary and all secondary diagnosis codes, infection was associated with 1826 (51%) of readmissions. Other common diagnoses associated with readmission included stroke-related codes (n=840, 23.7%) and aspiration pneumonitis (n=154, 4.3%). The most common infection-related primary diagnosis codes were septicemia (n=420, 11.8%), pneumonia (n=124, 3.5%), urinary tract infection (n=141, 4.0%), and gastrointestinal infection (n=42, 1.2%). Patients with a primary infection-related International Classification of Diseases, Ninth Revision, Clinical Modification code on readmission had higher in-hospital mortality compared with other types of readmission (15.6% versus 8.0%, P<0.001). After controlling for other predictors of mortality, primary infection-related readmissions remained associated with in-hospital mortality (relative risk, 1.7; 95% confidence interval, 1.3-2.2). CONCLUSIONS: Infections are associated with a majority of 30-day readmissions after intracerebral hemorrhage and increased mortality. Efforts should be made to reduce infection-related complications after hospital discharge.

Introduction Infections are common inpatient complications after intracerebral hemorrhage (ICH), but little is known about risk of infection after hospital discharge. Methods We performed a retrospective cohort study of patients discharged from non-federal acute-care hospitals in California with a primary diagnosis of ICH between 2006 and 2010. ICH was defined as a primary ICD-9CM discharge diagnosis code of 431. Only the first eligible ICH admission was included for each patient. Exclusion criteria were discharge against medical advice, in-hospital death, and non-California residency. After discharge from index admission, we assessed the proportion of readmissions to an acute-care hospital within 30 days that were related to infection. Clinical Classification Software (CCS) categorization of ICD-9CM codes was utilized for etiology of readmission. Inter-hospital transfers and readmission for likely planned procedures (craniotomy, embolization) were not included. Log-binomial regression was used to assess relationship between baseline characteristics and readmission mortality. Results There were 24,540 index ICH visits from 2006 to 2010. Unplanned readmissions occurred in 14.8% (n=3,269) of index patients. Of the 3,269 revisits, 934 (26%) had an infection-related primary diagnosis code. When evaluating all available revisit diagnosis codes, infection was associated with 1,945 (54%) of readmissions. Other common primary causes for readmission included stroke-related codes (n=894, 24.6%) and complications of medical/surgical care (n=92, 2.5%). The most common infection-related primary diagnosis codes were septicemia (n=422, 11.6%), respiratory infections/aspiration (n=292, 8.0%), urinary tract infection (n=141, 3.9%), and gastrointestinal infection (n=90, 2.5%). Patients with primary infection-related readmissions had higher in-hospital mortality compared to other types of readmission (15.7% vs. 7.7%, p< 0.001). After controlling for other predictors of mortality, primary infection-related readmissions remained associated with in-hospital mortality (RR=1.5, 95% CI 1.2-1.8). Conclusions Readmission for infection after ICH is common and associated with in-hospital death. Efforts should be made to identify ways to reduce infection-related complications in ICH patients after hospital discharge

OPINION STATEMENT: Neurologic injury is a common complication of major cardiovascular procedures including coronary artery bypass graft (CABG) surgery, coronary valve replacement, and aortic aneurysm surgery. However, despite ongoing research in the field of neuroprotection, there are currently few pharmacologic and interventional options to effectively protect the brain and spinal cord in the postoperative period. CSF drainage after aortic surgery currently stands as the only neuroprotective intervention that has been consistently shown to protect the spinal cord from ischemic injury, leading to significantly fewer patients with paraplegia and paraparesis. There is promising but conflicting evidence about the potential benefits of agents such as dexmedetomidine, lidocaine, magnesium, and erythropoietin in preventing postoperative stroke and cognitive dysfunction. Postoperative hypothermia has also been studied in preventing neurologic injury after cardiopulmonary bypass. With the rate of cardiovascular surgeries increasing yearly, further investigations are needed to validate many of these therapies and discover new ways to protect the brain and spinal cord from intraoperative and postoperative injuries in this high-risk population.

BACKGROUND: Treatment options for neuromyelitis optica (NMO) are currently based on small retrospective case series and open label studies, ranging from 10 to 103 patients. OBJECTIVE: To compare the efficacy and tolerability of azathioprine, cyclophosphamide, mycophenolate, and rituximab in patients with neuromyelitis optica. METHODS: This is a retrospective chart review and telephone follow-up study of 71 patients with NMO or NMO spectrum disorder, 54 of whom were treated with the study drugs. We compared adverse events, annualized relapse rates and expanded disability status scales before and after treatment. RESULTS: The median ARR decreased from 1.17 to 0.25 on rituximab (P<0.01), 0.92 to 0.56 on azathioprine (P=0.475), 1.06 to 0.39 on mycophenolate (P<0.05) and 1.30 to 0.92 on cyclophosphamide (P=0.746). When compared directly to azathioprine, rituximab significantly reduced relapse rates (P=0.021). The median EDSS decreased from 7 to 5 on rituximab (P<0.01) and 7 to 6 on azathioprine (P<0.01), and did not change significantly on mycophenolate (4 to 5; P=0.463) or cyclophosphamide (6.5 to 6.5; P=0.881). Twenty-five percent of patients noted adverse events on rituximab, 36% on azathioprine, 36% on mycophenolate, and 80% on cyclophosphamide. CONCLUSION: Rituximab significantly reduces relapse rates and improves disability while maintaining comparable tolerability to other immunosuppressive treatments for NMO.

While evidence suggests that transcranial direct current stimulation (tDCS) may facilitate language recovery in chronic post-stroke aphasia, individual variability in patient response to different patterns of stimulation remains largely unexplored. We sought to characterize this variability among chronic aphasic individuals, and to explore whether repeated stimulation with an individualized optimal montage could lead to persistent reduction of aphasia severity. In a two-phase study, we first stimulated patients with four active montages (left hemispheric anode or cathode; right hemispheric anode or cathode) and one sham montage (Phase 1). We examined changes in picture naming ability to address (1) variability in response to different montages among our patients, and (2) whether individual patients responded optimally to at least one montage. During Phase 2, subjects who responded in Phase 1 were randomized to receive either real-tDCS or to receive sham stimulation (10 days); patients who were randomized to receive sham stimulation first were then crossed over to receive real-tDCS (10 days). In both phases, 2 mA tDCS was administered for 20 min per real-tDCS sessions and patients performed a picture naming task during stimulation. Patients' language ability was re-tested after 2-weeks and 2-months following real and sham tDCS in Phase 2. In Phase 1, despite considerable individual variability, the greatest average improvement was observed after left-cathodal stimulation. Seven out of 12 subjects responded optimally to at least one montage as demonstrated by transient improvement in picture-naming. In Phase 2, aphasia severity improved at 2-weeks and 2-months following real-tDCS but not sham. Despite individual variability with respect to optimal tDCS approach, certain montages result in consistent transient improvement in persons with chronic post-stroke aphasia. This preliminary study supports the notion that individualized tDCS treatment may enhance aphasia recovery in a persistent manner.