Neurology October 2012 Volume 79 Issue 14

Objective: To explore the potential relationship between fatigue following strokes and poststroke mood, cognitive dysfunction, disability, and infarct site and to determine the predictive factors in the development of poststroke fatigue (PSF) following minor infarcts.Methods: Ninety-nine functionally active patients aged less than 70 years with a first, nondisabling stroke (NIH Stroke Scale score <=6 in acute phase and <=3 after 6 months, modified Rankin Scale score <=1 at 6 months) were assessed during the acute phase and then at 6 (T1) and 12 months (T2) after their stroke. Scores in the Fatigue Assessment Inventory were described and correlated to age, gender, neurologic and functional impairment, lesion site, mood scores, neuropsychological data, laboratory data, and quality of life at T1 and T2 using a multivariate logistic regression analysis in order to determine which variables recorded at T1 best predicted fatigue at T2.Result: As many as 30.5% of the patients at T1 and 34.7% at T2 (11.6% new cases between T1 and T2) reported fatigue. At both 6 and 12 months, there was a significant association between fatigue and a reduction in professional activity. Attentional-executive impairment, depression, and anxiety levels remained associated with PSF throughout this time period, underlining the critical role of these variables in the genesis of PSF. There was no significant association between the lesion site and PSF.Conclusion: This study suggests that attentional and executive impairment, as well as depression and anxiety, may play a critical role in the development of PSF.GLOSSARY: ACTH : adrenocorticotropic hormoneDSM-IV : Diagnostic and Statistical Manual of Mental Disorders, 4th editionFAI : Fatigue Assessment InstrumentHARS : Hamilton Anxiety Rating ScaleHDRS : Hamilton Depression Rating ScaleMS : multiple sclerosisNIHSS : NIH Stroke ScalePSF : poststroke fatigueTSH : thyroid-stimulating hormone(C)2012 American Academy of Neurology

Objective: To study the frequency and degree of deconditioning, clinical features, and relationship between deconditioning and autonomic parameters in patients with orthostatic intolerance.Methods: We retrospectively studied all patients seen for orthostatic intolerance at Mayo Clinic between January 2006 and June 2011, who underwent both standardized autonomic and exercise testing.Results: A total of 184 patients (84 with postural orthostatic tachycardia syndrome [POTS] and 100 without orthostatic tachycardia) fulfilled the inclusion criteria. Of these, 89% were women, and median age was 27.5 years (interquartile range [IQR] 22-37 years). Symptom duration was 4 years (IQR 2-7.8). Of the patients, 90% had deconditioning (reduced maximum oxygen uptake [VO2max%] <85%) during exercise. This finding was unrelated to age, gender, or duration of illness. The prevalence of deconditioning was similar between those with POTS (95%) and those with orthostatic intolerance (91%). VO2max% had a weak correlation with a few autonomic and laboratory parameters but adequate predictors of VO2max% could not be identified.Conclusion: Reduced VO2max% consistent with deconditioning is present in almost all patients with orthostatic intolerance and may play a central role in pathophysiology. This finding provides a strong rationale for retraining in the treatment of orthostatic intolerance. None of the autonomic indices are reliable predictors of deconditioning.GLOSSARY: BP: blood pressureDBP: diastolic blood pressureHR: heart rateHUT: head-up tiltIIE: early phase IIIIL: late phase IIMET: metabolic equivalentOI: orthostatic intolerancePOTS: postural orthostatic tachycardia syndromePP: pulse pressureRER: respiratory exchange ratioSBP: systolic blood pressureTST: thermoregulatory sweat testVM: Valsalva maneuverVO2max: maximum oxygen uptakeVR: Valsalva ratio(C)2012 American Academy of Neurology

Objectives: Given that multiple sclerosis (MS) hits diffusely the brain hemispheres, we hypothesized that this should result in a distributed pattern of functional connectivity (FC) abnormalities. To this aim, we assessed, using resting-state (RS) fMRI, intrinsic FC and functional network connectivity (FNC) of brain large-scale neuronal networks from 85 patients with relapsing-remitting MS (RRMS) and 40 matched controls.Methods: Independent component analysis was used to analyze RS fMRI data. Intrinsic FC of each cluster of each RS network (RSN) was compared between controls and patients (analysis of variance adjusted for age, gender, and gray matter volume). The FNC toolbox was used to assess interactions among RSNs.Results: Compared to controls, patients with RRMS experienced a decreased RS FC in regions of the salience (SN), executive control (ECN), working memory (WMN), default mode (DMN), sensorimotor, and visual networks. They also had an increased RS FC in regions of the ECN and auditory RSN. Decreased RS FC was significantly correlated with disability and T2 lesion volumes. In patients with RRMS, when compared to controls, FNC analysis showed that the ECN had an increased connectivity with the SN and a decreased connectivity with the DMN. An abnormal connectivity between the WMNs and sensory networks was also found.Conclusions: Functional abnormalities within and between large-scale neuronal networks occur in patients with RRMS and are related to the extent of T2 lesions and the severity of disability. Longitudinal studies should ascertain whether such functional abnormalities confer a systematic vulnerability to disease progression or, conversely, protect against the onset of clinical deficits.GLOSSARY: ANOVA: analysis of varianceCIS: clinically isolated syndromeDMN: default mode networkECN: executive control networkEDSS: Expanded Disability Status ScaleFC: functional connectivityFNC: functional network connectivityGM: gray matterGMV: gray matter volumeICA: independent component analysisIFG: inferior frontal gyrusITG: inferior temporal gyrusLV: lesion volumeMS: multiple sclerosisRRMS: relapsing-remitting multiple sclerosisRS: resting-stateRSN: resting-state networkSN: salience networkWMN: working memory network(C)2012 American Academy of Neurology

Objective: To describe the neurologic and neuroradiologic complications of Shiga toxin producing Escherichia coli infection (STEC)-associated hemolytic-uremic syndrome (HUS) in adults.Methods: All 52 adult patients with STEC O104:H4 infection cared for at Hannover Medical School during the outbreak in Germany through May-July 2011 are considered in this observational study. Forty-three of the 52 patients underwent a standard neurologic diagnostic procedure including clinical examination, Mini-Mental State Examination, and Glasgow Coma Scale Score. Thirty-six patients underwent EEG, and 26 had cerebral MRI, 9 of them repeatedly. Case records of 9 patients who had not been seen by a neurologist were analyzed retrospectively.Results: Forty-eight of the 52 patients had HUS. All but 1 of these showed neurologic symptoms. Focal neurologic signs like double vision, difficulties in finding words, or hyperreflexia were present in 23, additional deficits in orientation, attention, memory, or constructive abilities in 9, and marked impairment of consciousness in 15. MRI showed brainstem, midbrain, thalamus, corpus callosum, and white matter lesions in half of the patients, predominantly in diffusion-weighted images. The extent of MRI lesions did not correlate with clinical symptoms. General slowing but no focal alteration was found in half of the patients examined by EEG.Conclusion: Our findings suggest a toxic-metabolic pathology behind the neurologic impairment instead of multiple infarction due to microthrombosis. Future studies should aim to clarify if early antibiotic therapy or bowel cleansing might help to decrease the rate of neurologic complications in STEC-HUS.GLOSSARY: ADC: apparent diffusion coefficientCRP: C-reactive proteinHUS: hemolytic-uremic syndromeLDH: lactate dehydrogenaseMHH: Hannover Medical SchoolMMSE: Mini-Mental State ExaminationmRS: modified Rankin ScalePRES: posterior reversible encephalopathy syndromeROI: region of interestSTEC: Shiga toxin producing Escherichia coli infectionTPE: therapeutic plasma exchangeWBC: white blood cell(C)2012 American Academy of Neurology

Objective: An increased R2 recovery component of the blink reflex (R2-BRrc) has been commonly observed in Parkinson disease, cranio-cervical dystonia, and dystonic tremor, while the BRrc was reported normal in patients with essential tremor (ET). We studied BRrc in patients with ET associated with resting tremor (rET) in comparison with patients with ET.Methods: This was a cross-sectional study investigating R2-BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500, and 750 msec in 14 patients with rET, 14 patients with ET, and 16 healthy controls. To compare individual patients, we calculated an R2 recovery index in each subject as the mean of R2 area ratio values at ISIs of 150, 200, 300, 400, and 500 msec. All patients and controls underwent DAT-SPECT.Results: Patients with rET differed from those with ET for the presence of resting tremor associated in several cases (36%) with a subtle arm dystonia. DAT-SPECT was normal in all patients and controls. All patients with rET (with and without dystonia) had an increased R2-BRrc while all patients with ET had a normal BRrc comparable to that of control subjects. The R2 recovery index was abnormal in all patients with rET but in none of the patients with ET.Conclusions: Patients with rET showed increased R2-BRrc, suggesting that this form of tremor may be a dystonic tremor rather than a subtype of ET. BRrc helps to correctly diagnose DAT-negative patients with resting tremor also in the absence of overt dystonic posturing.GLOSSARY: ANOVA: analysis of varianceBRrc: recovery cycle of the blink reflexECR: extensor carpi radialisET: essential tremorFCU: flexor carpi ulnarisISI: interstimulus intervalMMSE: Mini-Mental State ExaminationPD: Parkinson diseaseR2-BRrc: R2 recovery component of the blink reflexrET: essential tremor associated with resting tremorSWEDD: scan without evidence of dopaminergic deficit.(C)2012 American Academy of Neurology

Objective: To assess the available evidence for the diagnostic accuracy of CSF testing for protein 14-3-3 in patients with suspected sporadic Creutzfeldt-Jakob disease (sCJD).Methods: The authors performed a systematic review of the available literature from 1995 to January 1, 2011, to identify articles involving patients who were suspected of having sCJD and who had CSF analysis for protein 14-3-3. Studies were rated according to the American Academy of Neurology classification of evidence scheme for diagnostic studies, and recommendations were linked to the strength of the evidence. A pooled estimate of sensitivity and specificity was obtained for all studies rated Class II or higher. The question asked is "Does CSF 14-3-3 protein accurately identify Creutzfeldt-Jakob disease (CJD) in patients with sCJD?"Results: The analysis was conducted on the basis of samples of 1,849 patients with suspected sCJD from 9 Class II studies. Assays for CSF 14-3-3 protein are probably moderately accurate in diagnosing sCJD: sensitivity 92% (95% confidence interval [CI] 89.8-93.6), specificity 80% (95% CI 77.4-83.0), likelihood ratio of 4.7, and negative likelihood ratio of 0.10.Recommendation: For patients who have rapidly progressive dementia and are strongly suspected of having sCJD and for whom diagnosis remains uncertain (pretest probability ~20%-90%), clinicians should order CSF 14-3-3 assays to reduce the uncertainty of the diagnosis (Level B).GLOSSARY: CI: confidence intervalCJD: Creutzfeldt-Jakob diseaseDWI: diffusion-weighted imagingFLAIR: fluid-attenuated inversion recoveryNSE: neuron-specific enolasePSWC: periodic sharp and slow wave complexesROC: receiver operator characteristicsCJD: sporadic Creutzfeldt-Jakob diseaseWB: Western blot.(C)2012 American Academy of Neurology

The role of the physician scientist in biomedical research is increasingly threatened. Despite a clear role in clinical advances in translational medicine, the percentage of physicians engaged in research has steadily declined. Several programmatic efforts have been initiated to address this problem by providing time and financial resources to the motivated resident or fellow. However, this decline in physician scientists is due not only to a lack of time and resources but also a reflection of the uncertain path in moving from residency or postdoctoral training toward junior faculty. This article is a practical guide to the milestones and barriers to successful faculty achievement after residency or fellowship training.(C)2012 American Academy of Neurology