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JOURNAL REVIEWSPredicting Parkinson’s disease dementiausing EEG microstructureThere is an urgent need for reliable biomarkers capable of predictingParkinson’s disease (PD) complications, particularly dementia. Whilstmost attention is given to genetics, brain imaging and biological fluidmarkers (mainly in CSF), Klassen et al from the Mayo Clinic set out todetermine whether quantitative EEG could fulfil this role.They longitudinally studied 106 PD patients (mean age = 76 years)following a baseline resting EEG. They excluded those taking anticonvulsantsand benzodiazepines. By collecting 100 seconds of EEG datawhen the patient was in a state of “relaxed wakefulness” (sat in recliningchair with eyes shut) and transforming this into its component waveforms,they calculated the global EEG bandpower for each of the fourfrequency bands (δ = 1.5-3.9 Hz, θ = 4-7.9 Hz, α = 8-12.9 Hz, β = 13-30 Hz).They also calculated the background rhythm frequency (BRF) whichwas defined as the dominant waveform present in the posterior electrodes.The mean follow-up duration was 3.3 years (range 0.31 - 8.8years), during which time patients underwent annual neuropsychologicaltesting to detect emerging PD dementia. Clinicians were blinded tothe baseline EEG.Using a Kaplan Meier curve, the incidence of dementia within 5 yearsof baseline EEG for the entire sample was 34%. Patients with mild cognitiveimpairment (MCI) at baseline had a hazard ratio (HR) of 4.3compared to those who did not. Surprisingly, age or PD duration at baselinedid not significantly alter dementia risk.After dichotomising at the median, patients with ‘low’ BRF (less thancut-off of 8.5 Hz) had a significantly greater dementia risk (HR 13)compared to those with ‘high’ BRF. This translates into a dementia incidencewithin 5 years of EEG of 66% compared to 8.1%. Those with ‘high’θ bandpower had a smaller but still significant increased incidence ofPD dementia (HR 3.0) compared to those with ‘low’ θ bandpower. Otherbandpowers did not significantly alter dementia risk. The BRF hazardwas not reduced in the multivariate modelling by more than 15% byeither PD-MCI or any of the other neuropsychological tests. The authorsbelieve that this supports the argument that BRF truly predicts dementiarisk rather than simply acting as a surrogate marker of current cognitivedeficits. θ bandpower, on the other hand, was confounded by both PDduration and MMSE.The authors hypothesise that structural pathology in PD may interferewith the normal background alpha rhythm generated by subcorticaland corticocortical circuits, thereby resulting in a downward spectralshift (i.e. slowing) of the BRF frequency. However, they acknowledge thatfurther work is needed to understand the neural substrates of cognitivedeterioration in PD.The findings are interesting but do they help our PD patients? In theshorter term, it and other biomarkers may allow enrichment of neuroprotectivedrug trials with cognitively ‘at-risk’ patients. The usefulness ofquantitative EEG in detecting cognitive decline and predicting futurerisk on an individual basis still needs to be proven in larger studies withlonger follow-up, and the need for specialist training and equipmentshould be borne in mind. Nonetheless, the concept of using EEGmicrostructure to predict disease progression is an exciting one.– Dr David P Breen, Clinical Research Fellow in Neurology, CambridgeCentre for Brain Repair.Klassen BT, et al. Quantitative EEG as a predictor biomarker forParkinson’s disease dementia. NEUROLOGY 2011;77:118-24.Graft and blockDiaphragmatic paralysis is a major complication of high cervical cordinjury. Unfortunately, many patients sustaining such injuries requirelong-term mechanical ventilation with its myriad of associated complicationsand obvious negative impact on quality of life. A bleak outlook,most would agree. Alilain et al, however, writing in Nature, provide hopefor those left in this desperate state. Using rats receiving C2 hemisectionas their model of injury, the authors describe their experiments thateventually lead to apparent recovery of diaphragmatic innervation onthe lesioned side.It is known that the extracellular space within the mature spinal cordcontains chondroitin sulphate proteoglycans (CSPGs), creating a potentinhibitory environment for neuronal regeneration. Moreover, it is knownthat this inhibitory extracellular matrix is upregulated at sites of injury.Firstly, Alilain et al. show that enzymatic breakdown of this inhibitoryextracellular matrix at the level of the phrenic nerve nuclei leads toincreased number of serotonergic neurons, known to be involved inrespiratory plasticity. Although functional recovery was disappointing,the authors then investigated the effects of implanting autologous nervegrafts in addition to enzymatic treatment, hypothesising that theSchwann cells contained in the grafted nerve would provide the necessaryfactors and support to guide lesioned axons to the denervatedphrenic nerve nuclei ipsilateral and caudal to the C2 hemisection.Remarkably, by 12 weeks, the hemisectioned rats receiving both enzymaticbreakdown of CSPGs and peripheral nerve grafts showedrecovery of ipsilateral diaphragmatic function, often surpassing measuresof activity compared to the contralateral side and the diaphragmsof uninjured animals. Importantly, the authors show that recovery isdependent on the implanted nerve graft as transection leads tocomplete loss of ipsilateral diaphragmatic activity.Time will tell whether these findings can be translated in order tohelp patients who have sustained high cervical cord injuries.Furthermore, Alilain et al.’s work points again to the remarkable potentialability of the nervous system to regenerate, given the appropriateenvironment, and gives hope that such approaches may be applied to awide range of neurological injuries in the context of neurorehabilitationin years to come.– Dr Rhys Roberts, Honorary Consultant in Neurology, Addenbrooke’sHospital, Cambridge.Alilain WJ, Horn KP, Hu H, Dick TE and Silver J. Functional regenerationof respiratory pathways after spinal cord injury.NATURE 2011;475:196-200.Ambu ® Inoject NeedlesThe main points Used for relaxation of muscles that are spasmodic inthe face, particularly around the eyes, head and neck. Help bring relief to sufferers of cerebral palsy andother genetic nerve diseases that cannot be relaxedby manipulation, including laryngeal spasms.The rangeProducts with pre-attached lead wiresSix colour coded sizes from 25mm length0.30mm calibre to 75mm length0.55mm calibreTel: 01480 498 403Fax: 01480 498 405email: uksales@ambu.comWeb: www.ambu.co.uk46 > <strong>ACNR</strong> > VOLUME 11 NUMBER 4 > SEPTEMBER/OCTOBER 2011
NEWS REVIEWPediatric Neurology – A Color HandbookThis new book is written byspecialist authors whorecognise the needs ofnonspecialists and trainees.Recognising patterns ofdisease can be the first stepto successful management ofthe child with a neurologicalproblem; this is emphasisedby the authors throughoutthe book. Their concise,precise account reflects theremarkable recent advancesin paediatric neurology andrelated disciplines, whilestressing the fundamentals ofclinical examination andhistory taking in reaching anaccurate diagnosis. The bookbegins with a detailed discussion of neurologicalexamination techniques and the basic formulationof differential diagnoses and management, usingneuroradiology, electrophysiology, cerebrospinalfluids, genetic and metabolic testing. The secondsection of the book follows a problem-basedIncrease in sales of Ambu’s Inoject needleAmbu are a Danish headquartered company with animpressive portfolio of products. One product that is nowmaking its way into many hospital departments and has seena recent increase in demand is the Inoject needle used forEMG procedures. When asked why use of this needle seemedto be more frequent Chris Smith, UK sales manager for therange, replied “ The Inoject needle provides superiorperformance with reduced friction for ease of skinpenetration and a high quality signal for consistent reliableresults, helping in the accurate use of Botulinum for manyconditions. Inoject needles are currently being used for therelaxation of muscles that are spasmodic in the face,particularly around the eyes, head and neck. The needles alsohelp bring relief to sufferers of cerebral palsy and othergenetic nerve diseases, as well as general nerve spasms thatcannot be relaxed by manipulation, including laryngealspasms. These high quality products are available in a fullrange of sizes and I believe this is reflected in their popularity.”For more information Email. skg@ambu.comapproach, just as diseasespresent in the real world. Itemploys practical, symptomandsign-based strategies forvirtually all conditionsencountered by thepractitioner. The final sectionon neurological emergenciesrecognises that suchconditions present first tosomeone other than apaediatric neurologist.Authors: James F Bale,Joshua L Bonkowsky, FrancisM Filloux, Gary L Hedlund,Denise M Nielsen, Universityof Utah School of Medicine,Salt Lake City, Utah, USA, PaulD Larsen, University ofNebraska College of Medicine, USA.ISBN 9781840761344.For more informationEmail. matt@mansonpublishing.comMerck Serono submitsapplication forextension ofindication for Rebif®in EuropeMerck Serono, a division of Merck KGaA,Darmstadt, Germany has submitted an applicationto the European Medicines Agency (EMA) to extendthe indication of Rebif®, its leading treatment formultiple sclerosis (MS). The requested labelextension is for the use of Rebif® in patients whohave experienced a single demyelinating event, anearly sign of the disease, and who are at high risk ofconverting to MS.“Our application to extend the indication ofRebif® is based on the REFLEX study, which focusedon patients with early signs of multiple sclerosis,”said Dr. Bernhard Kirschbaum, Executive VicePresident for Global Research and Development atMerck Serono. “We remain strongly committed toaddressing the medical needs of patients withmultiple sclerosis at the various stages of thisdevastating disease.”Merck Serono’s submission of a type II variationto extend the indication of Rebif® is supported byresults of the REFLEX study, which were presentedat the American Academy of Neurology (AAN) inApril 2011. The REFLEX study was designed toevaluate the effect of two different doses of Rebif– the currently approved 44mcg three times a weekand 44mcg once a week – versus placebo, on the“Time to conversion to McDonald MS (2005)” inpatients with a first clinical demyelinating event andhaving magnetic resonance imaging (MRI) brainscans consistent with early signs of MS. The studymet its primary endpoint for both doses bydemonstrating that Rebif® significantly delayedconversion to McDonald MS (2005) in thosepatients.The REFLEX study was conducted with thehuman serum albumin (HSA) – free formulation ofRebif®, which is now available in all European Unioncountries, Australia, Canada and Switzerland, as wellas a number of countries in Asia, Latin America,Africa and the Middle East. The HSA-freeformulation of Rebif® is currently not available inthe United States.Tremendous achievement of climbers with MS or PDIn July, 7 men and women withMultiple Sclerosis (MS) and 4 withParkinson’s disease (PD), along withnine climbing companions, reachedthe highest peak in Africa. This is thefirst time that a group of people withboth of these neurodegenerativediseases have united to reach asummit this high. The climb clearlydemonstrated that neurodegenerativediseases do not represent the end of‘normal’ life. Mount Kilimanjaro in Tanzania stands at 19,340 feet, not onlymaking it the highest peak in Africa, but also the highest free-standingmountain in the world.“This ‘Kilimanjaro Leap of Faith Adventure’ was meant to challenge thebody, expand the mind and foster courage in dealing with the diagnosis of aneurodegenerative disease. There have been some really tough parts of thetrek, especially altitude sickness, for which there is nothing you can do.Imagine that on top of our neurodegenerative diseases. But, we’ve made itand that’s a credit to all of us whobelieve that we can go beyond thelimitations of our disease and stillachieve incredible results, bothphysically and mentally,” said triporganiser Lori Schneider, founder ofEmpowerment Through Adventure.“Most of the group dedicatedthemselves to training to preparethemselves for this challenge. A keyattribute of the group is theiroutstandingly positive outlook, regardless of the hurdles they face, and theirunwavering commitment to supporting one another throughout the trip”.Communication activities for the Kilimanjaro Leap of Faith Adventure2011 are kindly supported by Sanofi.For further information on Empowerment Through Adventuresee www.EmpowermentThroughAdventure.com<strong>ACNR</strong> > VOLUME 11 NUMBER 4 > SEPTEMBER/OCTOBER 2011 > 47
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