Neurology July 2012 Volume 79 Issue 4

Objectives: Efficacy of thrombolytic therapy for ischemic stroke decreases with time elapsed from symptom onset. We analyzed the effect of interventions aimed to reduce treatment delays in our single-center observational series.Methods: All consecutive ischemic stroke patients treated with IV alteplase (tissue plasminogen activator [tPA]) were prospectively registered in the Helsinki Stroke Thrombolysis Registry. A series of interventions to reduce treatment delays were implemented over the years 1998 to 2011. In-hospital delays were analyzed as annual median door-to-needle time (DNT) in minutes, with interquartile range.Results: A total of 1,860 patients were treated between June 1995 and June 2011, which included 174 patients with basilar artery occlusion (BAO) treated mostly beyond 4.5 hours from symptom onset. In the non-BAO patients, the DNT was reduced annually, from median 105 minutes (65-120) in 1998, to 60 minutes (48-80) in 2003, further on to 20 minutes (14-32) in 2011. In 2011, we treated with tPA 31% of ischemic stroke patients admitted to our hospital. Of these, 94% were treated within 60 minutes from arrival. Performing angiography or perfusion imaging doubled the in-hospital delays. Patients with in-hospital stroke or arriving very soon from symptom onset had longer delays because there was no time to prepare for their arrival.Conclusions: With multiple concurrent strategies it is possible to cut the median in-hospital delay to 20 minutes. The key is to do as little as possible after the patient has arrived at the emergency room and as much as possible before that, while the patient is being transported.GLOSSARY: BAO: basilar artery occlusionDNT: door-to-needle timeEMS: emergency medical serviceER: emergency roomINR: international normalized ratioIQR: interquartile rangemRS: modified Rankin ScaleNIHSS: NIH Stroke ScaleNNT: number needed to treatOTT: onset-to-treatment timePOC: point-of-careRCT: randomized controlled trialstPA: tissue plasminogen activator(C)2012 American Academy of Neurology

Objective: We aimed to determine whether amyloid imaging can help predict the location and number of future hemorrhages in cerebral amyloid angiopathy (CAA).Methods: We performed a longitudinal cohort study of 11 patients with CAA without dementia who underwent serial brain MRIs after baseline amyloid imaging with Pittsburgh compound B (PiB). Mean distribution volume ratio (DVR) of PiB was determined at the sites of new micro/macrobleeds identified on follow-up MRI and compared with PiB retention at "simulated" hemorrhages, randomly placed in the same subjects using a probability distribution map of CAA-hemorrhage location. Mean PiB retention at the sites of observed new bleeds was also compared to that in shells concentrically surrounding the bleeds. Finally the association between number of incident bleeds and 3 regional amyloid measures were obtained.Results: Nine of 11 subjects had at least one new microbleed on follow-up MRI (median 4, interquartile range [IQR] 1-9) and 2 had 5 new intracerebral hemorrhages. Mean DVR was greater at the sites of incident bleeds (1.34, 95% confidence interval [CI] 1.23-1.46) than simulated lesions (1.14, 95% CI 1.07-1.22, p < 0.0001) in multivariable models. PiB retention decreased with increasing distance from sites of observed bleeds (p < 0.0001). Mean DVR in a superior frontal/parasagittal region of interest correlated independently with number of future hemorrhages after adjustment for relevant covariates (p = 0.003).Conclusions: Our results provide direct evidence that new CAA-related hemorrhages occur preferentially at sites of increased amyloid deposition and suggest that PiB-PET imaging may be a useful tool in prediction of incident hemorrhages in patients with CAA.GLOSSARY: A[beta]: [beta]-amyloidCAA: cerebral amyloid angiopathyCI: confidence intervalDVR: distribution volume ratioIQR: interquartile rangePiB: Pittsburgh compound BROI: region of interestSWI: susceptibility-weighted imaging(C)2012 American Academy of Neurology

Objective: To characterize the phenotype of spinocerebellar ataxia type 36 (SCA36), a novel dominant disorder (nicknamed "Asidan") caused by a hexanucleotide GGCCTG repeat expansion in intron 1 of the NOP56 gene.Methods: We investigated the clinical, genetic, and neuropathologic characteristics of 18 patients with SCA36. We performed histologic evaluation of a muscle biopsy specimen from 1 patient with SCA36, and neuropathologic evaluation of an autopsied brain from another patient with SCA36.Results: The (GGCCTG)n expansion was found in 18 ataxic patients from 9 families. The age at onset of ataxia was 53.1 +/- 3.4 years, with the most frequent symptoms being truncal ataxia (100% of patients), ataxic dysarthria (100%), limb ataxia (93%), and hyperreflexia (79%). Tongue fasciculation and subsequent atrophy were found in 71% of cases, particularly in those of long duration. Skeletal muscle fasciculation and atrophy of the limbs and trunk were found in 57% of cases. Lower motor involvement was confirmed by EMG and muscle biopsy. The neuropathologic study revealed significant cerebellar Purkinje cell degeneration with obvious loss of lower motor neurons. Immunohistochemical analysis showed that NOP56 was localized to the nuclei of various neurons. Cytoplasmic or intranuclear inclusion staining of NOP56, TDP-43, and ataxin-2 was not observed in the remaining neurons.Conclusions: This is the first description of the unique clinical features of SCA36, a relatively pure cerebellar ataxia with progressive motor neuron involvement. Thus, SCA36 is a disease that stands at the crossroads of SCA and motor neuron disease.GLOSSARY: ALS: amyotrophic lateral sclerosisCMAP: compound muscle action potentialeZIS: easy Z-score imaging systemH&E: hematoxylin & eosinMCP: middle cerebellar peduncleMCV: motor nerve conduction velocityNADH-TR: nicotinamide adenine dinucleotide-tetrazolium reductaseNCS: nerve conduction studySARA: Scale for Assessment and Rating of AtaxiaSCA: spinocerebellar ataxiaSCV: sensory nerve conduction velocitySNAP: sensory nerve action potential99mTc-ECD: 99mTc-ethylcysteinate dimer(C)2012 American Academy of Neurology

Objective: To determine the most critical symptoms in a national myotonic dystrophy type 1 (DM1) population and to identify the modifying factors that have the greatest effect on the severity of these symptoms.Methods: We performed a cross-sectional study of 278 adult patients with DM1 from the national registry of patients with DM1 between April and August 2010. We assessed the prevalence and relative significance of 221 critical DM1 symptoms and 14 disease themes. These symptoms and themes were chosen for evaluation based on prior interviews with patients with DM1. Responses were categorized by age, CTG repeat length, gender, and duration of symptoms.Results: Participants with DM1 provided symptom rating survey responses to address the relative frequency and importance of each DM1 symptom. The symptomatic themes with the highest prevalence in DM1 were problems with hands or arms (93.5%), fatigue (90.8%), myotonia (90.3%), and impaired sleep or daytime sleepiness (87.9%). Participants identified fatigue and limitations in mobility as the symptomatic themes that have the greatest effect on their lives. We found an association between age and the average prevalence of all themes (p < 0.01) and between CTG repeat length and the average effect of all symptomatic themes on participant lives (p < 0.01).Conclusions: There are a wide range of symptoms that significantly affect the lives of patients with DM1. These symptoms, some previously underrecognized, have varying levels of importance in the DM1 population and are nonlinearly dependent on patient age and CTG repeat length.GLOSSARY: DM1: myotonic dystrophy type 1FDA: Food and Drug AdministrationFSHD: facioscapulohumeral muscular dystrophyPRISM-1: Patient Reported Impact of Symptoms in Myotonic Dystrophy Type 1.(C)2012 American Academy of Neurology

Objective: To investigate the relation between retinopathy and the risk of dementia.Methods: We investigated the associations between retinopathy and dementia and its subtypes Alzheimer disease (AD) and vascular dementia both cross-sectionally and prospectively in the Rotterdam Study, a large population-based cohort study. Digitized retinal images were available for 195 participants with prevalent dementia and 6,078 participants without dementia at baseline (1990-1993). Participants were reexamined in 1993-1994, 1997-1999, and 2002-2004 and were continuously monitored for development of dementia until January 1, 2007. Retinopathy was graded on fundus photographs and was defined as the presence of one or more dot/blot hemorrhages, microaneurysms, cotton wool spots, or evidence of laser treatment for retinopathy.Results: Retinopathy was associated with prevalent dementia (age and sex-adjusted odds ratio 2.04, 95% confidence interval [CI] 1.34-3.09). Results were similar for AD and vascular dementia. During a mean follow-up of 11.4 years, 735 participants developed incident dementia, of whom 583 had AD and 80 had vascular dementia. There was no association of retinopathy at baseline with the risk of incident dementia during follow-up (age- and sex-adjusted hazard ratio 1.15, 95% CI 0.88-1.48) or the risk of incident AD or vascular dementia.Conclusions: Retinopathy is more prevalent in persons with dementia but is not associated with an increased risk of dementia over time.GLOSSARY: AD: Alzheimer diseaseARIC: Atherosclerosis Risk in CommunitiesCI: confidence intervalCRP: C-reactive proteinDSM-III-TR: Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revisedGMS: Geriatric Mental State scheduleMMSE: Mini-Mental State ExaminationOR: odds ratio(C)2012 American Academy of Neurology

Objectives: Video-sharing Web sites are being used for information about common conditions including dizziness. The Epley maneuver (EM) is a simple and effective treatment for benign paroxysmal positional vertigo (BPPV) of the posterior canal. However, the maneuver is underused in routine care. In this study, we aimed to describe and analyze the available information about the EM on youtube.com.Methods: A YouTube search was performed on August 31, 2011, for videos that demonstrated the entire EM. Detailed data were abstracted from each video and corresponding Web site. Videos were rated on the accuracy of the maneuver by 2 authors, with differences resolved by adjudication. Comments posted by viewers were assessed for themes regarding video use.Results: Of the 3,319 videos identified, 33 demonstrated the EM. The total number of hits for all videos was 2,755,607. The video with the most hits (802,471) was produced by the American Academy of Neurology. Five of the videos accounted for 85% of all the hits. The maneuver demonstration was rated as accurate in 64% (21) of the videos. Themes derived from the 424 posted comments included patients self-treating with the maneuver after reviewing the videos, and providers using the videos as a prescribed treatment or for educational purposes.Conclusion: Accurate video demonstration of the Epley maneuver is available and widely viewed on YouTube. Video-sharing media may be an important way to disseminate effective interventions such as the EM. The impact of video Web sites on outcomes and costs of care is not known and warrants future study.GLOSSARY: BPPV: benign paroxysmal positional vertigoEM: Epley maneuver(C)2012 American Academy of Neurology