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Hong Kong Med J Vol 19 No 6 # Supplement 6 # December 2013 1

3rd Hong Kong Neurological Congress cum 26th Annual Scientific Meeting of The Hong Kong Neurological Society

Council of The Hong Kong Neurological Society 4

Organising Committee 4

List of Speakers 5

Scientific Programme 6

SESSION ABSTRACT PAGE

FREE PAPER PRESENTATIONSPilot Study for Subgroup Classification for Autism Spectrum FP 1 9Disorder Based on Dysmorphology and Physical Measurements in Chinese Paediatric and Adolescent PopulationPolly TY Wong, Virginia CN Wong

Promotion of Physical Activity and Fitness in the Parki-Fit & FP 2 10Walk Program Addressing the Non-motor Symptom ‘Fatigue’ for Idiopathic Parkinson’s Disease CM Kwok, HT Lui, LF Hui, KY Wong

Cryptococcal Meningitis FP 3 11Helen Yip, MC Kwan, WK Cheng, WY Lau, KF Ko

A Young Lady with Artery of Percheron Infarction and Patent FP 4 12Foramen OvaleSH Li, TY Wai, MF Ip, KK Ma

Clinical and Genetic Evaluation of 23 Children with Infantile- FP 5 13onset Epileptic EncephalopathyAlvin CC Ho, Anna KY Kwong, CW Fung, Virginia CN Wong

DISSERTATION HIGHLIGHTSMorbidity and Mortality of Guillain-Barré Syndrome in DH 1 14Hong KongAnna HY Wong

Intracerebral Haemorrhage in Patients Warfarinised for Non- DH 2 14valvular Atrial Fibrillation (NVAF) and the Use of HAS-BLED Score in Addition to CHA2DS2-VASc Score to Refine the Decision on Anticoagulation for NVAF PatientsMK Fong

Volume 19 # Number 6 # DECEMBER 2013

S U P P L E M E N T 6

Editor-in-ChiefIgnatius TS Yu 余德新

Senior EditorsPT Cheung 張璧濤CB Chow 周鎮邦

Albert KK Chui 徐家強Michael G Irwin

TW Wong 黃大偉

EditorsKL Chan 陳廣亮KS Chan 陳健生

Henry LY Chan 陳力元David VK Chao 周偉強

TW Chiu 趙多和Stanley ST Choi 蔡兆堂

LW Chu 朱亮榮WK Hung 熊維嘉

Bonnie CH Kwan 關清霞 Alvin KH Kwok 郭坤豪

Paul BS Lai 賴寶山Eric CH Lai 賴俊雄

Stephen TS Lam 林德深Patrick CP Lau 劉志斌Arthur CW Lau 劉俊穎Nelson LS Lee 李禮舜

Danny WH Lee 李偉雄KY Leung 梁國賢

Danny TN Leung 梁子昂Thomas WH Leung 梁慧康

WK Leung 梁惠強Kenneth KW Li 李啟煌

David TL Liu 劉大立Janice YC Lo 羅懿之

Herbert HF Loong 龍浩鋒James KH Luk 陸嘉熙Ronald CW Ma 馬青雲

Ada TW Ma 馬天慧 Henry KF Mak 麥嘉豐

Jacobus KF Ng 吳國夫Hextan YS Ngan 顏婉嫦

Martin W Pak 白威Edward CK So 蘇超駒

PC Tam 談寶雛William YM Tang 鄧旭明Martin CS Wong 黃至生

Kenneth KY Wong 黃格元Patrick CY Woo 胡釗逸

Bryan PY Yan 甄秉言TK Yau 游子覺

Kelvin KH Yiu 姚啟恒

Advisors on BiostatisticsWilliam B Goggins

Eddy KF Lam 林國輝

Advisor on Clinical Epidemiology Shelly LA Tse 謝立亞

2 Hong Kong Med J Vol 19 No 6 # Supplement 6 # December 2013

SESSION ABSTRACT PAGEStudy on the Safety and Efficacy of Dabigatran Etexilate DH 3 15(Pradaxa®) in Stroke Prevention on Hong Kong Chinese with Atrial Fibrillation as Compared with Warfarin: a Local Hospital ExperienceKK Ma

Acute Ischaemic Stroke in Patients with Atrial Fibrillation DH 4 16and Their Use of WarfarinEric YC Leung

SYMPOSIUM ON STROKERecent Advances in Stroke Imaging S 1 17PW Cheng

Intracranial Stenting S 2 18WM Lui

SYMPOSIUM ON EPILEPSYClinical Use of Electroencephalography: Ten Years After S 3 19the Millennium Ziyi Chen

The Mechanism of Neural Tube Defects Induced by S 4 19Antiepileptic DrugsLiemin Zhou

Ketogenic Diet / Modified Atkin’s Diet for Epilepsy S 5 20Phyllis YP Yau, Eva LW Fung

SYMPOSIUM ON MOVEMENT DISORDERS AND NEURODEGENERATIONManagement of Gait Disorders in Parkinson’s Disease: a S 6 20Neurologist’s PerspectiveGermaine HF Chan

Rehabilitation of Gait Disorders in Parkinson’s Disease S 7 21Margaret Mak

The Therapeutic Effect of Hepcidin in Parkinson’s Disease S 8 21Via Regulation of Brain Iron and α-Synuclein AccumulationYa Ke

Mechanism of Deep Brain Stimulation in Parkinsonism: S 9 22Direct Involvement of the Primary Motor CortexWH Yung

SYMPOSIUM ON DEMENTIA AND NEURODEGENERATIONSpinocerebellar Ataxia in Chinese S 10 23Anne YY Chan, Edwin HY Chan

Individualised Stem Cell Therapy S 11 24Ken KL Yung

Identification and Characterisation of a Cognitive Enhancer S 12 24from Traditional Chinese MedicineFanny CF Ip, Nancy Y Ip


SESSION ABSTRACT PAGE

LUNCH SYMPOSIUMTreatment of Refractory Multiple Sclerosis S 13 25Finn Sellebjerg

SYMPOSIUM ON NEUROLOGIC INFECTIONIntracranial Abscesses and Infections of Neurosurgical S 14 25Shunts and DrainsYW Fan

The ‘Not So Common’ Causes of Central Nervous System S 15 26Infection in Hong Kong: Diagnoses You Cannot Afford to MissJasper FW Chan

SYMPOSIUM ON NEUROLOGY HIGHLIGHTTen Minutes Vestibular Examinations but Persistent S 16 26Rehabilitative ExercisesDennis KK Au

Neurostimulation in Primary Headache Disorders S 17 27Raymond CK Chan

Late-onset Pompe Disease in the New Enzyme Replacement S 18 27Therapy EraBun Sheng

POSTERSExperience of Using Intravenous Thrombolysis in Elderly P 1 28Patients with Major Acute Ischaemic Stroke in Kwong Wah HospitalHelen Yip, MC Kwan, WK Cheng, WY Lau, KF Ko, TY Chan, ML Lai

Griffiths Mental Developmental Scales Validation for Chinese P 2 28ChildrenWinnie WY Tso, LI Ao, M Li, X Zhang, FY Jiao, X Xu, KX Du, XL Xia, Denise Challis, Virginia CN Wong

The Prognosis of Acute Symptomatic Seizures after Ischaemic P 3 29StrokeT Leung, H Leung, Y Soo, C Leung, V Mok, KS Wong

INDEX 30

INTERNATIONAL EDITORIAL ADVISORY BOARD

Sabaratnam Arulkumaran United Kingdom

Robert AtkinsAustralia

Peter CameronAustralia

David ChristianiUnited States

James DickinsonCanada

Adrian DixonUnited Kingdom

Willard Fee, JrUnited States

Robert HoffmanUnited States

Sean HughesUnited Kingdom

Arthur KleinmanUnited States

Xiaoping LuoChina

Jonathan SametUnited States

Rainer SchmelzeisenGermany

Homer YangCanada

EXECUTIVE EDITOR

Cyrus R Kumana

MANAGING EDITOR

Yvonne Kwok 郭佩賢

DEPUTY MANAGING EDITOR

Betty Lau 劉薇薇

ASSISTANT MANAGING EDITOR

Warren Chan 陳俊華


Council of The Hong Kong Neurological Society

President DrJonasHon-mingYeung楊漢明醫生Vice-President DrWing-chiFong方榮志醫生HonSecretary ProfVincentChung-tongMok莫仲棠教授HonTreasurer DrKwok-kwongLau劉國光醫生CouncilMembers DrRaymondChun-kongChan陳振江醫生 DrEricLok-yiuChan陳樂耀醫生 DrWing-keungCheng鄭永強醫生 DrChun-mingCheung張春明醫生 DrNelsonYuk-faiCheung張煜暉醫生 DrGardianChung-yanFong方頌恩醫生 ProfThomasWai-hongLeung梁慧康教授 DrColinHiu-tungLui呂曉東醫生 DrBunSheng盛斌醫生 DrAlanChoi-tingTse謝采庭醫生 DrWinnieWing-yinWong黃詠妍醫生AdHocMember DrTak-hongTsoi蔡德康醫生PastPresident DrLeonardSheung-waiLi李常威醫生HonLegalAdvisor MrTsang-hoiKoo顧增海律師HonAuditor MrEricLi李家祥先生

Organising Committee of the 3rd Hong Kong Neurological Congress cum 26th Annual Scientific Meeting of The Hong Kong Neurological Society

Chairmen DrWing-chiFong方榮志醫生 DrJonasHon-mingYeung楊漢明醫生(Co-Chair)Secretary ProfVincentChung-tongMok莫仲棠教授Treasurer DrKwok-kwongLau劉國光醫生ScientificCommittee DrRaymondChun-kongChan陳振江醫生 DrEricLok-yiuChan陳樂耀醫生 DrWing-keungCheng鄭永強醫生 DrChun-mingCheung張春明醫生 DrNelsonYuk-faiCheung張煜暉醫生 DrGardianChung-yanFong方頌恩醫生 ProfThomasWai-hongLeung梁慧康教授 DrColinHiu-tungLui呂曉東醫生PublicationCommittee DrChi-namLee李至南醫生 DrAlanChoi-tingTse謝采庭醫生 DrWinnieWing-yinWong黃詠妍醫生Website DrBunSheng盛斌醫生


List of Speakers

Name Affiliation

DrDennisKin-kwokAu TheUniversityofHongKong,HongKongSAR

DrAnneYin-yanChan PrinceofWalesHospital,HongKongSAR

DrEdwinHo-yinChan TheChineseUniversityofHongKong,HongKongSAR

DrGermaineHiu-faiChan QueenElizabethHospital,HongKongSAR

DrJasperFuk-wooChan TheUniversityofHongKong,HongKongSAR

DrRaymondChun-kongChan UnitedChristianHospital,HongKongSAR

ProfZiyiChen TheFirstAffiliatedHospital,Zhongshan(SunYatSen)

University,China

DrPui-waiCheng StTeresa’sHospital,HongKongSAR

DrYiu-wahFan Privatepractice,HongKongSAR

ProfFannyCFIp TheHongKongUniversityofScience&Technology,

HongKongSAR

ProfYaKe TheChineseUniversityofHongKong,HongKongSAR

DrAlexanderYuk-lunLau PrinceofWalesHospital,HongKongSAR

ProfThomasWai-hongLeung PrinceofWalesHospital,HongKongSAR

DrPatrickChung-kiLi QueenElizabethHospital,HongKongSAR

DrWai-manLui QueenMaryHospital,HongKongSAR

DrMargaretKit-yiMak TheHongKongPolytechnicUniversity,HongKongSAR

ProfFinnSellebjerg CopenhagenUniversityHospital,Denmark

DrBunSheng PrincessMargaretHospital,HongKongSAR

MsPhyllisYin-pingYau PrinceofWalesHospital,HongKongSAR

ProfKenKin-lamYung TheHongKongBaptistUniversity,HongKongSAR

ProfWing-hoYung TheChineseUniversityofHongKong,HongKongSAR

ProfLieminZhou TheFirstAffiliatedHospital,Zhongshan(SunYatSen)

University,China


SCIENTIFIC PROGRAMME

Venue: Lecture HaLL, 7/F, BLock H, Princess Margaret HosPitaL, Hong kong sar

2 noVeMBer 2013, saturday

08:30 – 09:00 Registration Lobby

09:00 – 10:15 FREE PAPER PRESENTATIONChairpersons: Wing-keung Cheng, Winnie Wing-yin Wong

POSTER PRESENTATION

10:15 – 10:45 CoffeeBreak/PosterViewing10:45 – 12:15 DISSERTATION HIGHLIGHTS

Chairpersons: Wing-keung Cheng, Winnie Wing-yin Wong

12:15 – 13:00 Lunch13:00 – 13:15 OPENING CEREMONY

Guest of Honour: The Hon Dr Wing-man Ko, BBS, JP, Secretary of Food and Health

13:15 – 14:45 SYMPOSIUM ON STROKEChairpersons: Chen-ya Huang, Chun-ming Cheung

Recent Advances in Stroke ImagingPW Cheng

External counterpulsationThomas WH Leung

Intracranial StentingWM Lui

14:45 – 15:05 CoffeeBreak15:05 – 16:35 SYMPOSIUM ON EPILEPSY

Chairpersons: Jason Ka-yeung Fong, Eric Lok-yiu Chan

Clinical Use of Electroencephalography: Ten Years After the Millennium

Ziyi Chen

The Mechanism of Neural Tube Defects Induced by Antiepileptic Drugs

Liemin Zhou

Ketogenic Diet / Modified Atkin’s Diet for EpilepsyPhyllis YP Yau, Eva LW Fung

18:00 FacultyDinner(byinvitationonly)


08:30 – 09:00 Registration Lobby

09:00 – 10:30 SYMPOSIUM ON MOVEMENT DISORDERS AND NEURODEGENERATION

Chairpersons: Mandy Au-yeung, Kin-lun Tsang

Management of Gait Disorders in Parkinson’s Disease: a Neurologist’s Perspective

Germaine HF Chan

Rehabilitation of Gait Disorders in Parkinson’s DiseaseMargaret Mak

The Therapeutic Effect of Hepcidin in Parkinson’s Disease Via Regulation of Brain Iron and α-Synuclein Accumulation

Ya Ke

Mechanism of Deep Brain Stimulation in Parkinsonism: Direct Involvement of the Primary Motor Cortex

WH Yung

POSTER PRESENTATION

10:30 – 10:50 CoffeeBreak10:50 – 12:20 SYMPOSIUM ON DEMENTIA AND

NEURODEGENERATIONChairpersons: Vincent CT Mok, Ken KL Yung

Spinocerebellar Ataxia in ChineseAnne YY Chan, Edwin HY Chan

Individualised Stem Cell TherapyKen KL Yung

Identification and Characterisation of a Cognitive Enhancer from Traditional Chinese Medicine

Fanny CF Ip, Nancy Y Ip

3 noVeMBer 2013, sunday

(Cont’donp.8)


12:20 – 12:50 Lunch Lobby

12:50 – 13:40 LUNCH SYMPOSIUMChairperson: Kwok-kwong Lau

Treatment of Refractory Multiple SclerosisFinn Sellebjerg

Case SharingAlexander YL Lau

POSTER PRESENTATION

13:40 – 15:10 SYMPOSIUM ON NEUROLOGIC INFECTIONChairpersons: Richard Kay, Alan CT Tse

Neurological Vignette of HIV-infected PatientsPatrick CK Li

Intracranial Abscesses and Infections of Neurosurgical Shunts and Drains

YW Fan

The ‘Not So Common’ Causes of Central Nervous System Infection in Hong Kong: Diagnoses You Cannot Afford to Miss

Jasper FW Chan

15:10 – 15:25 CoffeeBreak15:25 – 16:55 SYMPOSIUM ON NEUROLOGY HIGHLIGHT

Chairpersons: Shi-hon Ng, Bun Sheng

Ten Minutes Vestibular Examinations but Persistent Rehabilitative Exercises

Dennis KK Au

Neurostimulation in Primary Headache DisordersRaymond CK Chan

Late-onset Pompe Disease in the New Enzyme Replacement Therapy Era

Bun Sheng

16:55 – 17:05 ClosingRemarks&AwardPresentation

3 noVeMBer 2013, sunday(Cont’d)


Pilot Study for Subgroup Classification for Autism Spectrum Disorder Based on Dysmorphology and Physical Measurements in Chinese Paediatric and Adolescent Population

Polly TY Wong, Virginia CN WongDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong SAR

Background: Autismspectrumdisorder(ASD)isdefinedasarangeofcomplexneurodevelopmentaldisorderaffecting individualsalongacontinuumofseverity incommunication,social interactionandbehaviour.TheimpactofASDsignificantlyvariesamongindividuals,andthecauseofASDcanoriginatebroadlybetweengeneticandenvironmentalfactors.PreviousASDresearchesindicatethatearlyidentificationcombinedwithatargetedtreatmentplaninvolvingmultidisciplinarytherapiesandbehavioural interventionscanbringaboutsubstantial improvementtothedevelopmentofautisticpatients.CurrentlythereisnocureforASD,andtheclinicalvariabilityanduncertaintyofthedisorderstillremains.Hence,thesearchtounravelheterogeneitywithinASDbysubgroupclassificationmayprovideclinicianswithabetterunderstandingofASDandallowforamoredefinitivecourseofaction.Methods:Inthisstudy,anormofphysicalmeasurementsincludingheight,weight,headcircumference,ear length,outerand innercanthus, interpupillarydistance,philtrum,handandfoot lengthwerecollectedfrom658normalChinesechildrenaged1to7years.Thenormcollectedwascomparedagainst80ChineseASDchildrenaged1to12years.WeattemptedtofindsubgroupswithinASDsubjectsbasedonidentifyingphysicalabnormalities; individualswereclassifiedas(non)dysmorphicwiththeAutismDysmorphologyMeasure(ADM)ScoringAlgorithmfromphysicalexaminations.Results: Ourresultsshowedthattherewasasignificantdifference(P<0.05)betweenage-matchednormalcontrolsandASDgroupinmeasurementsforheadcircumference,outerandinnercanthus,philtrumlength,rightandleftfootlength.Withinthe80ASDpatients,39weredefinedasdysmorphic(P=0.00).Conclusion: This study attempted to identify subgroups within ASD patients based on physicalmeasurementsanddysmorphologyexaminations.TheinformationfromthisstudyseekstobenefitASDcommunitybyidentifyingthepossiblesubtypesofASDinChinesepreschoolpopulation,andtoseekforamoredefinitivediagnosis,referral,andtreatmentplan.

FP 1


Promotion of Physical Activity and Fitness in the Parki-Fit & Walk Program Addressing the Non-motor Symptom ‘Fatigue’ for Idiopathic Parkinson’s Disease

CM Kwok1, HT Lui2, LF Hui2, KY Wong1

1 Physiotherapy Department, Integrated Rehabilitation Services, Tseung Kwan O Hospital, Hong Kong SAR2 Division of Neurology, Department of Medicine, Tseung Kwan O Hospital, Hong Kong SAR

Introduction: IdiopathicParkinson’sdisease(iPD)isoftencomplicatedwithvariousmotorandnon-motorsymptoms,whichhasgreatimpactindailyfunctions,fitness,andqualityoflife(QoL)wellbeing.Fatigueisoneofthecommonirritatingnon-motorsymptoms.Itoftenappearsasanobstacletodailyphysicalexerciseadherence.However, limitedclinicalresearchaddressedits impactsduringtheprocessofrehabilitation.Objectives:(1)Toevaluatetheimpactofnon-motorsymptom,fatigue,onhealthfitness,QoLandamountofphysicalactivityafterparticipatingtheParki-Fit&WalkProgram;and(2)todeterminethepredictingfactorscontributingtothechangeofendurancecapacitythroughphysicalexerciseindailyliving.Methods: AfteriPDpatientsreceivedpharmacologicalcontrolfromNeurologyClinicandIntegratedPDService,indicatedpatientswillberecruitedintheParki-fit&WalkProgramfor6months.ItwasdesignedformultifacetedbehaviouralchangewithvariousstrategiestoachievebetterQoLandhealthfitness,viapromotingactivelifestyletowardsmoderatephysicalactivitylevel.Theamountofphysicalactivitywasmeasuredbyastandardised7-dayrecallquestionnaire(PhysicalActivityRecallQuestionnaire[PARQ]).Detailsofprogramworkflowinclude20iPDpatientsinthe‘fatigue’group(FG)and26inthe‘non-fatigue’group(NFG).Theywereidentifiedbyemployingthe9-itemFatigueSeverityScale(FSS),whichreflectedphysicalandmentalfatigue.Theindividualscoreofthemeanofthenumericalresponseswascalculated;acut-offof4wasusedtoselectfatiguedfromnon-fatigued.Results:TheNFGincreasedby70%andtheFG increasedby49.6%in totalenergyexpenditureofmoderatephysicalactivities(P=0.001;repeatedmeasuredANOVA)afterintervention.Theyallachievedtherecommendedmoderatephysicalexerciselevel.Bothgroupsobtainedobvioushealthfitnessgain.Motorcontrol(UPDRSmotorscore)improvedby33%inNFGand6.4%inFG;walkingendurance(6-minutewalkdistance)improvedby32.5%inNFGand0.6%inFG;comfortgaitspeedimprovedby33.8%inNFGand4.3%inFG;QoLwellbeing(MotorscoreinParkinson’sdisease39Questionnaire)improvedby67.4%inNFGand6.4%inFG(P=0.001;repeatedmeasuredANOVA).Thelinearstepwisemultivariateregressionanalysisshowedthechangeofwalkingendurancewasassociatedwithchangeofgaitspeedandchangeofmoderatelevelphysicalexercises(P=0.000).Thismodelpredicted61%correctly(R2=0.61).Thechangeofendurancecapacitycanbepredictedbythefollowingequation:15.24+161.168xchangeofgaitspeed+0.05xchangeofmoderatelevelphysicalexercisesenergyexpenditure(n=46,R2=0.61,P=0.000).Conclusion:Thestudysuggestedthatearlymultidisciplinaryteamapproachincludedcomprehensiveevaluation,customiseddiseasemanagementandtrainingprogramliketheParki-fit&WalkProgramwillfacilitateholisticcareiniPD.Determiningthefatiguelevelmayfacilitatespecialisededucation,exercisedosageprescription,andprogramadherence.Furtherresearchesarerecommendedtostudyitslong-termeffectonhealthcareoutcomes.

FP 2


Cryptococcal Meningitis

Helen Yip, MC Kwan, WK Cheng, WY Lau, KF KoDepartment of Medicine and Geriatrics, Kwong Wah Hospital, Hong Kong SAR

Wereportacaseofcryptococcalmeningitisinanimmunocompetentmalepresentedwithfeverfor4monthsdespiteextensivework-up. A63-year-oldmanHongKongresidentwho isa retiredshopkeeperwithamedicalhistoryofhypertensionand lumbarspondylosis.HepresentedtoourMedicalUnit formentaldullnesswithdecreasedshort-termmemory.Beforecurrentadmission, thepatientwasadmittedtoOurLadyofMaryknollHospital for4-monthhistoryofpyrexiaandrecentlydiagnosedpulmonarycryptococcalinfectionconfirmedwith lungbiopsybeingputon4daysof fluconazole therapyprior tocurrentadmission. Onexamination,thepatientwasafebrilewithaGlasgowComaScalescoreofE4M6V4.Neckrigiditywasnegative.Limbmusclepowerwasequalandsymmetrical.Plantarswerebilaterallyflexor.Laboratoryinvestigationsrevealedraisedtotalleukocytecount(whitecellcount[WCC],15x109/L).Bloodforrenalfunctiontestsandliverfunctiontestswerenormal.Cerebrospinalfluid(CSF)examinationrevealedWBC168/cm3withpredominantlylymphocytes67%,withproteinof7.03g/Landglucoseof0.9mmol/L(correspondingbloodglucosewas6.0mmol/L). TherewerenomicroorganismsonGramandZiehl-Neelsen(Z-N)stains.Indiainkexaminationwasnegativewithanegativegrowthonbacterialculture.TheCSFandserumcryptococcalantigenwerepositive,withatitreof1:256withcultureyieldCryptococcus neoformans. Acomputedtomography(CT)scanofthebrainshowedhypodensityoverrightcaudatenucleusandLtpontinearea.Mini-MentalStateExamination(MMSE)was19outof30onadmission.Hiscomplementandimmunoglobulinlevelswerewithinnormallimits.Anti-HIVantibodywasnegativeintwobloodsamples3monthsapart. HewasstartedonantifungalpharmacotherapywithamphotericinBwithadditionofflucytosine(5FC)asinductiontherapy.SubsequentMMSEwas26outof30after3weeksofantifungaltreatment.Fluconazolewasfollowedasconsolidationandmaintenancetherapy. Mostcasesofcryptococcalmeningitisoccur in immunocompromisedpatientsbut ithasbeenreportedinHIV-negativepatientscausedbychemotherapy-relatedimmunosuppression,historyoforgantransplantation,haematologicalmalignancies,concurrentuseofcorticosteroidtherapy,andsarcoidosis.Occasionally,noobviousunderlyingcausecanbedetected. Cryptococcalmeningitisremainsadevastatingdiseasewithahighmortality.Animportantpredictorofearlymortalityisanabnormalmentalstatusatpresentationandmortalitycanbeupto25%.Otherprognosticfactorsincludebaselinehigh-openingpressure,poorWCCresponseinCSF,highCSFtitresofcryptococcalantigen>1024,positivebloodcultureandCSFIndiaink/Gramstainpositivity. Ourpatienthadagradual improvement incognitionandmobilityafterprompttreatment.Earlydiagnosisandmanagementisessentialtohastenrecoveryincryptococcalmeningitis.

FP 3


A Young Lady with Artery of Percheron Infarction and Patent Foramen Ovale

SH Li, TY Wai, MF Ip, KK MaDepartment of Medicine, North District Hospital, Hong Kong SAR

A30-year-oldwomanattendedNeurologyClinicatNorthDistrictHospitalinMarch2010forinvestigationofdiplopia.Shecomplainedofaperiodofimpairedconsciousnessfollowedbydiplopiain2003whenshewasinMainlandChina.Shereportedgradualrecoveryafterwardsthoughresidualdiplopiaremained.Shehadnoheadorneckinjury.Sheenjoyedgoodpasthealth. Neurologicalexaminationshowedimpaireddownwardgaze(pursuitandsaccade).Otherpartsofexaminationwereunremarkable.Shedidnothaveanylimbweaknessorataxia.Hercognitivewasunremarkable.Computedtomographicnon-contrastbrainrevealedbilateral thalamicandanteriormidbrainoldinfarcts(Fig1).ElectrocardiogramandchestX-raywerenormal.Bloodtestsforfastingglucose,lipid,renalandliverfunctiontest,completebloodpicture,clotting,erythrocytesedimentationratewerenormal.Immunemarkers(ANA,DNA,ENA,andANCA)werenegative.Anti-cardiolipinantibody,proteinCandS,andanti-thrombinIIIwerealsonormal.Magneticresonance imagingof thebrainshowedoldinfarctsatbilateralparamedianthalamiandleftrostralmidbrain(Figs2and3)suggestingoldinfarctionfromocclusionofarteryofPercheron.Moreover,multiplelacunarinfarctswerenotedinbilateralcoronaradiata,frontalandparietalwhitematter,lefttemporallobeandleftcentrumsemiovale.Magneticresonanceangiographyofthecerebral,carotidandvertebralarterieswereunremarkable(Fig4).ThoroughinvestigationsforheryoungstrokeincludingcarotidduplexultrasoundandtranscranialDoppler(TCD)ultrasound,transthoracicechocardiogramaswellasHoltertestwereallunremarkable.BubbleTCDwas thenperformedthatrevealedonemicroembolicsignalafterValsalvamanoeuvresuggestiveoflow-graderight-to-leftshunt.Transesophagealechocardiogramwasfinallyperformedwhichconfirmedthepresenceofpatentforamenovalethatcanaccountforherpriorstroke. Shehasbeengivenclopidogrel75mgdailyorallysince2010asshehasaspirinallergy.ShedeliveredanormalbabyuneventfullyinJune2011.Shehasnothadstrokerecurrence.

FP 4

Fig 1 Fig 2 Fig 3 Fig 4


Clinical and Genetic Evaluation of 23 Children with Infantile-onset Epileptic Encephalopathy

Alvin CC Ho, Anna KY Kwong, CW Fung, Virginia CN WongDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Queen Mary Hospital / Duchess of Kent Children’s Hospital, Hong Kong SAR

Background: Infantileepilepticencephalopathies(IEE)areagroupofconditions inwhichcognitive,sensory,and/ormotorfunctionsdeteriorateasaconsequenceofepilepticactivities,whichconsistoffrequentseizuresand/ormajorinterictalparoxysmalactivity.TherearevariouscausesofIEEandtheymayoccuratanyage.Methods:Wereviewedpatients in theDepartmentofPaediatricsandAdolescentMedicineof theUniversityofHongKong,QueenMaryHospitalandDuchessofKentChildren’sHospitalwiththeclinicaldiagnosisofIEEofunknownaetiologyovera10-yearperiod(2003-2012).Fivegenes(ARX, CDKL5, KCNQ2, SCN1A,andSTXBP1)werescreenedusingsequencing.Results:Atotalof23patientswereidentifiedandtheirelectroclinicalfeatureswerestudied.Ofthe23patients,10(43.5%)hadepilepticspasmasthepresentingseizuretype.Throughouttheclinicalcourse,patientswerecharacterisedbyfrequentseizuresthatweremultiformandpharmaco-resistant.Thecommonestsubsequentseizuretypewasgeneralisedtonic/clonic/tonic-clonicseizure(17outof23,73.9%).Allofthepatientshaddevelopmentaldelayofvariousdegrees.Movementdisorderintermsofdystoniawasthemostcommonassociatedclinicalfeature(10outof23,43.5%).Fivegenes(ARX, CDKL5, KCNQ2, SCN1A,andSTXBP1)werescreenedin20ofourpatients.WeidentifiedthreepatientswithSTXBP1mutations, twopatientswithSCN1Amutations,andonepatientwithKCNQ2mutation.Theoveralldetectionratewas30%(6/20).TwooutofthreepatientswithDravetphenotypewerescreenedpositiveforSCN1Amutation.TheonlypatientwithtypicalOhtaharaphenotypewasscreenedpositiveforSTXBP1mutation.Conclusion: ThisstudyhighlightedtheclinicalcharacteristicsofIEEandstudiedtheyieldofmutationalscreeningoffiveselectedgenesinthisgroupofpatients.DravetsyndromeandOhtaharasyndromehavecharacteristicphenotypes.SCN1AandSTXBP1mutationalanalysisshouldbeperformedinchildrenwithclassicpresentationsoftheabove-namedconditionsrespectively.

FP 5


DH 1

DH 2

Morbidity and Mortality of Guillain-Barré Syndrome in Hong Kong

Anna HY WongDepartment of Medicine, Queen Elizabeth Hospital, Hong Kong SAR

Objectives:ToreviewtheclinicalprofileandoutcomeofpatientswithGuillain-Barrésyndrome(GBS)managedinhospitals inHongKongandto lookforanypredictorsformechanicalventilation,poordisabilityoutcome,andmortality.Methods:SubjectssufferingfromGBSadmittedtoQueenElizabethHospital,PrincessMargaretHospital,andCaritasMedicalCentrefromJanuary2001toDecember2010wereincluded.Patientsyoungerthan18yearsoldorsufferingfromneuropathyotherthanGBSorincompletemedicalrecordavailableforreviewwereexcluded.Amultivariateanalysiswasusedforanalysisofpredictorsofoutcome.Results:Atotalof104patientswereincluded.Whencomparingbetweencohortsofthreehospitals,theyshowedsimilarbaselinecharacteristicsandoutcome.HigherErasmusGBSoutcomescoreandErasmusGBSrespiratoryinsufficiencyscorewereassociatedwithpooreroutcome,thoughtheassociationwasnotalwaysstatisticallysignificantamongthreecohorts.GBSdisabilityscoreonadmissionandageweresignificantpredictorsofmechanicalventilation(oddsratio=3.0;95%confidenceinterval,1.64-5.52;P<0.0001)andmortality(oddsratio=1.1;confidenceinterval,1.03-1.17;P=0.007),respectively.Nosignificantpredictorcouldbeidentifiedforindependencyofdailylivingat6months.Conclusion:ThemedianageandmortalityrateofGBSinHongKongwashigherwhencomparedtothoseofpreviousstudies.Amongthethreelocalhospitalsstudied,baselinecharacteristicsandoutcomeweresimilar.AgeandGBSdisabilityscoreonadmissionweresignificantlyrelatedtomortalityandriskofmechanicalventilationrespectivelywhileErasmusGBSoutcomescoreandErasmusGBSrespiratoryinsufficiencyscoreonadmissioncanserveasareferenceinpredictingoutcomeofpatientswithGBS.

Intracerebral Haemorrhage in Patients Warfarinised for Non-valvular Atrial Fibrillation (NVAF) and the Use of HAS-BLED Score in Addition to CHA2DS2-VASc Score to Refine the Decision on Anticoagulation for NVAF Patients

MK FongDepartment of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong SAR

Background: Atrialfibrillation(AF)canresult incatastrophicthromboemboliccomplications.Warfarinreducesthromboembolicriskbutisunderutilisedforthefearofmajorbleeding.CHA2DS2-VAScandHAS-BLEDscoresarehelpfulforriskstratification.Objectives: PartI—TocomparetheCHA2DS2-VAScandHAS-BLEDscoresamongwarfarinisednon-valvularAF(NVAF)patientswithandwithoutintracerebralhaemorrhage(ICH).PartII—Tostudytheclinicalcourseandoutcomeofwarfarin-relatedICH.Methods:ThreepatientgroupsinPrincessMargaretHospital(PMH),QueenElizabethHospital(QEH),andCaritasMedicalCentre(CMC)wereretrospectivelystudied:Case—warfarinisedNVAFpatientswithICH(PMH/QEH/CMC)during1January2006to31December2011;PartIreference—warfarinisedNVAFpatients(PMH)withoutICHduring1July2011to31October2011;PartIIcontrol—non-warfarinICHpatients(PMH)matchedwiththecasegroupforgender,age(±1year),andadmissionyear,inone-to-oneratio.Results: InPart I,114casesand661referenceswererecruited.ThecasegrouphadahighermedianCHA2DS2-VAScscore(5vs4;P=0.011)andmorepatientsinhigh-bleedingriskcategorythanreferencegroup(46.5%vs36.6%;P=0.033).Mostanticoagulatedpatients (99.1%)hadappropriatebenefit-riskbalance.InPartII,themeanadmissioninternationalnormalisedratio(INR)was2.8.Eighty-two(73.2%)patientshadICHdespiteadmissionINRdidnotexceedtherapeuticrange(INR≤3.0).InitialICHvolumeswerecomparableamongcaseandcontrolgroups.Amajorityofpatients inbothgroupshadpoorfunctionaloutcomeat6months.Warfarin-relatedICHhadahigherin-patientmortality(51.8%vs36.0%;P=0.02)and6-monthmortality(60.5%vs43%;P=0.01)thannon-warfarinICH.LoweradmissionGlasgowComaScalescore(P=0.001),higherinitialICHvolume(P=0.003),andhigherICHscore(P<0.001)werepredictorsofpooroutcome.Conclusion:Warfarin-relatedICHinNVAFpatientshadsignificantmorbidityandmortality.CHA2DS2-VAScscoreandHAS-BLEDscoreareusefulriskstratificationtoolstoguidetreatmentinNVAFpatients.


Study on the Safety and Efficacy of Dabigatran Etexilate (Pradaxa®) in Stroke Prevention on Hong Kong Chinese with Atrial Fibrillation as Compared with Warfarin: a Local Hospital Experience

KK MaDepartment of Medicine, North District Hospital, Hong Kong SAR

Background:TheuseofanticoagulantforstrokepreventioninatrialfibrillationisraisingconcerninHongKong.Warfarinwastheonlyoralanticoagulantavailableinthemarketbeforethelaunchofdabigatranetexilate.Thebenefitofnewanticoagulantisreportedasnon-inferiortowarfarinonstrokeprevention.Besides,patientswouldbenefitfromlessfood-and-drugrestrictioninviewofrelativelessinteraction.Thus,itcanprovidearelativestableanticoagulationeffectscomparedwithwarfarin.However,therearenolocaldataontheefficacyandsafetyontheuseofdabigatranetexilateinHongKong.Objective:TostudythesafetyandefficacyofdabigatranetexilateinstrokepreventiononHongKongChinesewithatrialfibrillation.Methods:ThiswasaretrospectivephaseIVpostmarketstudy.Patientsondabigatranetexilatefrommedicalspecialistout-patientclinicinNorthDistrictHospitalbetweenJanuary2009andAugust2012wererecruitedinthestudy.Thesafetyissueofthedabigatranetexilatewasdefinedastheincidenceofmajorbleedingincludingintracranialhaemorrhage,andminorbleeding,gastro-intestinalcomplicationsandhypersensitivityreaction.Theefficacyofthedabigatranetexilatewasinvestigatedbypatientoutcomes.Theprimaryoutcomewasrecurrent ischaemicstrokeortransient ischaemicattack.Thesecondaryoutcomewasthemortalityincidence.TheoveralldatawerecomparedwithAsianandnon-AsiandatafromRELYstudyuponthedabigatrantreatmentarmsandwarfarinarm.ThedatawerereviewedbyFebruary2013.Results:Atotalof96patientswereenrolledinthestudy.Themeanfollow-upperiodwas16months.Ourpatientsweremoreadvanceinageandmultipleco-morbiditieswithhigherCHADS2scores.Thestrokeratewas3.37%peryearwhichwashigherwhencomparedwiththedabigatrantreatmentandwarfarinarminRELYstudyas1.39%and2.50%peryear,respectively.Fourpatientsgotinterrupteddabigatranusebeforethestrokeevents.Themortalityratewas3.37%peryearascomparedwithdabigatrantreatmentandwarfarinarminRELYstudyas4.01%and5.01%peryear,respectively.Themajorandminorbleedingriskswere4.69%and1.56%, respectively,whichwere lowerwhencomparedwith thedabigatrantreatmentarmandwarfarinarminRELYstudy.Conclusions:ThemortalityandmajoradverseeventrateswerecomparablebetweenourstudydataandtheRELYstudyintheAsiangroupandnon-Asiangroup.Thehigherstrokerateinourstudymayberelatedtotheinterrupteddabigatranusesuchasprolongeddrugwithdrawalbeforeprocedure,afterminorbleedingorinappropriatedosage.Furtherstudywithlargersamplesize,longerstudyperiod,andcomparablecontrolarmarerecommended.

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DH 4Acute Ischaemic Stroke in Patients with Atrial Fibrillation and Their Use of Warfarin

Eric YC LeungDepartment of Medicine, Ruttonjee Hospital, Hong Kong SAR

Objectives:Atrialfibrillation(AF)isastrongindependentriskfactorforischaemicstroke(IS).Currentguidelinessuggestanticoagulationasaclass1ArecommendationforpatientswithISandAF(IS/AF).WeinvestigatedanydifferencebetweenISpatientswithandwithoutAF,andfactorsassociatedwiththeirinitiationandcontinuationofwarfarin.Methods:Across-sectionalretrospectivestudyutilisingthestrokeregistryofPamelaYoudeNethersoleEasternHospitalfrom2009to2010wasconducted.Atotalof824ISpatientswithAF(n=216)andwithoutAF(n=608)wereexaminedfordifferenceindemographics,strokesubtypes,strokeseverity,treatments,andoutcomes.Univariateanalysiswasusedtodetermineanyassociation(s)withincreasedlikelihoodof1-yearre-strokeordeath.Warfarinprescription,itsuseagainsttheCHADS2scores,reason(s)fornotprescribingwarfarin,warfarininitiationandterminationintheyearpost-dischargewereexaminedinIS/AFpatients.Results:OurIS/AFpatientswereolder,morelikelytobefemale,tohaveischaemicheartdiseaseandmoreseverestroke,toreceiveacutethrombolysis,andweremoredisabledbytheirstroke.ANIHSSscoreof≥5ondischarge,age≥80years,GlasgowComaScalescore (GCS)≤12,andmRS≥4wereassociatedwith increased likelihoodof1-yearmortality.Only61(32.1%)of theIS/AFpatientswereprescribedwarfarinondischarge;warfarinprescriptionwashighestinpatientswithCHADS2scoreof2.Nine(8.0%)ofIS/AFpatientsnotgivenwarfarinondischarge(n=112) initiatedwarfarinandseven(11.5%)of thewarfarinisedpatients (n=61)stoppedwarfarin, in theyear followingdischarge.At12months,58(42.0%)patientswerestillusingwarfarin.Thethreemostfrequentlydocumentedreasonsfornotprescribingwarfarinwerepoorfunctionalstatus,noreasongiven,andbleedingrisk.60%ofourwarfarinisedpatientsspent100%timewithininternationalnormalisedratio(INR)rangeof1.5-3.0,butonly12%ifthetargetINRrangewas2.0-3.0.Conclusions:TheoveralluseofwarfarininourIS/AFpatientsremainedlow.Possibleexplanationsincludecliniciansandpatientperceptionsofhighcomplication(s)riskwithwarfarinandtheunderestimationofstrokeriskfromAF.CliniciansareencouragedtousetheHAS-BLEDscorewiththeCHADS2orCHA2DS2-VAScscoreswhenconsideringpatientsforanticoagulation.


Recent Advances in Stroke Imaging

PW ChengScanning Department, St Teresa’s Hospital, Hong Kong SAR

Withtheadventofmagneticresonance(MR)andcomputedtomography(CT) imagingtechniques,imaginghasbecomean indispensable tool to thediagnosisandmanagementofstrokepatients.Advancedstrokeimagingalsoplaysapivotalroleinselectionandmonitoringofpatientsbeingtreatedbyendovascularorintravenousintra-arterialrecanalisationtherapy. ConventionalMRimaging,especially thediffusion-weightedsequence,hasvastly improvedthesensitivityandspecificityfordetectionofacutestrokeascomparedwithCTscanintheearlydays.Thefirstpartofthistalkwillfocusontheessentialpearlsandpitfallsincontemporaryacutestrokeimagingsoastoimprovediagnosticaccuracyinourdailyclinicalpracticebyrecognisingcommoncriticalartefacts.Neuroimagingscoresforacutestrokeandintra-cerebralhaemorrhagewillalsobebrieflyreviewed. Secondly, thecontinuallyevolvingmulti-modalityandmulti-parametricstrokeimagingapproachwillbeelaborated.Advanced imagingtechniquessuchasCTangiography,CTperfusion,dynamicsusceptibilityperfusion-weightedMRimaging,arterialspin-labellingperfusion-weightedMRimagingareincreasinglyemployedfortriageofpatientsfortailoredacutestroketherapyaswellasevaluationofchronicischaemicstroke. Emergingnovelstrokeimagingtechniquessuchasdiffusiontensorandpermeabilityimagingwillalsobeaddressedinthecontextoftheirpotentialclinicalapplication.Thevariousdirectionsforfuturestrokeimagingresearchwillbehighlighted,includingnon-invasivevulnerableplaqueimaging,recanalisationstrategiesoverextendedtimewindowetc.

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Intracranial Stenting

WM LuiDepartment of Neurosurgery, Queen Mary Hospital, Hong Kong SAR

Intracranial stent as an adjunct to endovascular embolisation/coilingRecenttechnologicaladvanceshaveledtothedevelopmentofadjunctivedevicesandtechniquestoimprovetheresultswithendovascularembolisation/coiling.Thesearedevicesthathelpcoilsstayinsidetheaneurysmsacwhichcanbeparticularlyhelpfulforaneurysmswithwidenecksorlargeaneurysmsthatweredifficulttotreatwithembolisation/coilinginthepast. Onesuchadjunctivedeviceisanintracranialstent.Astentisametalmeshdeviceintheshapeofapipeortubewhichisplacedinsidetheparentarteryatthesiteoftheaneurysmtocovertheneckoftheaneurysm.Thishelpstokeepcoilsplacedintheaneurysmsactostayinsidethesac. Thestentsareusuallymadeofnitinol,ahigh-grademetalalloyofnickelandtitanium.Oneormoreantiplateletmedicinessuchasaspirin,clopidogrel,ticlopidine,orothersarerequiredtopreventthromboembolismafterstentplacement.Therefore,theuseofstentinemergencysituationwithpriorantiplateletcoveragecarriescertainrisk. At the time of the embolisation/coiling procedure, or sometimes as a separate treatment, amicrocatheterandwirearenavigatedfromtheaccesssite(usually thefemoralartery inthegroin)usingX-rayvisualisationuptothesiteoftheaneurysminthebrain.Thestentcanbepushedthroughthemicrocatheteranddeployedattheintendedtargettocovertheaneurysmalneck.Thenanothermicrocatheterisnavigatedthroughthestentstrutandplacedinsidetheaneurysmsac.Thencoilsareplacedintheaneurysmsacaswouldbeperformedasdescribedinthecoilingdescription.Thestentwillpreventthecoilsfromenteringtheparentarteryandinsodoing,acompleteocclusionoftheaneurysmsacismadepossible.

Flow diverters—pipeline embolisation deviceApprovedbytheFoodandDrugAdministrationinApril2011,thepipelineembolisationdevice(PED)isaflexiblemeshtubemadeofplatinumandnickel-cobaltchromiumalloythatcanbeusedtoblockofflarge,giant,orwide-neckedaneurysmsintheintracranialarteries.Thedevicecanalsoreducethelikelihoodthatananeurysmwillrupture. Toimplantthedevice,thepipelineisattachedtotheendofacatheter.Thecatheteristhreadedintothecarotidarteryandintopositionattheaneurysmwherethepipelineisexpandedagainstthewallsofthearteryandacrosstheneckoftheaneurysm,cuttingoffbloodflowtotheaneurysm.Thebloodremainingintheblocked-offaneurysmformsaclotwhichreducesthelikelihoodtheaneurysmwillgrowbiggerorrupture.Aneurysmssuccessfullytreatedwiththepipelinewilloftenshrinkovertime.

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Clinical Use of Electroencephalography: Ten Years After the Millennium

Ziyi ChenDepartment of Neurology, The First Affiliated Hospital, Zhongshan (Sun Yat Sen) University, PR China

Theelectroencephalography(EEG),whichisentirelyharmlessandrelativelyinexpensive, isthemostimportant investigation in thediagnosisofepilepsies. In2001, ILAETaskForceestablishedanewdiagnosticschemeforpeoplewithepilepticseizuresandwithepilepsy:ictalphenomenology,seizuretype,syndrome,aetiology,andimpairment.IamgoingtoshowsomeexamplesofclinicaluseofEEGinthenewdiagnosticscheme.First,theparoxysmaleventshouldbedifferentiatedbetweenepilepticseizureandnon-epilepticattack.Sincetheepilepticseizurehasbeendefinedasatransientoccurrenceofsignand/orsymptomsduetoabnormalexcessiveneuronalactivityinthebrain,synchronousEEGmaybethekeymethodfordifferentiation.Weshouldpayattentiontothosepatientswithrealepilepticseizureandpseudoseizures.Second,thetypeofepilepticseizuresshouldbeconfirmed.Video-EEGisparticularlyimportantintheidentificationandcategorisationofepilepticseizures.HereIamgoingtosharebothsometypicalcasesofclassicepilepticseizuretypes(suchasgeneralisedtonic-clonicseizure,absenceseizure,atonicseizure),andsomenewtypes(suchaseyelidmyoclonia).Third,theepilepticsyndromeorepilepticdiseaseshouldbeclearlydiagnosed.Theepilepticsyndromeisdefinedasanepilepticdisordercharacterisedbyaclusterofsignsandsymptomscustomarilyoccurringtogether.Therearedifferentcharacteristicsindifferentepilepticsyndrome.Forexample,electricalstatusepilepticusinsleep(ESES)isrelatedtoLandau-Kleffnersyndrome(acquiredepilepticaphasia)andepilepsywithcontinuousspike-and-wavesduringslow-wavesleep(ECSWS).Insummary,EEGrecordingisofgreatdiagnosticsignificanceinclinicalpracticesbecauseitisassociatedwithclinicalmanifestations.

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S 4The Mechanism of Neural Tube Defects Induced by Antiepileptic Drugs

Liemin ZhouNeurological Department, The First Affiliated Hospital, Sun Yet-Sen University, Guangzhou 510080, PR China

Neuraltubedefects(NTDs)areamongthemostprevalentandmostseverecongenitalmalformationsworldwide.Polymorphisms inkeygenes involving the folatepathwayhavebeenreported tobeassociatedwiththeriskofNTDs.Valproicacid(VPA)isoneofthefirstlineantiepilepticdrugs(AEDs)andwidelyusedtocontrolmostsubtypesofseizures.SomewomenwithepilepsyduringpregnancyneedtobetreatedbyVPA,whichhoweverwillincreasetheriskofNTDsfromthedataofEURAPandtheNorthAmericanAEDPregnancyRegistry.Atpresent,theteratogenicmechanisminducedbyVPAisstillunclear.Boththegeneticpolymorphismoffolatemetabolicenzymesandvalproicacidtherapycanaffectgenetranscriptionthroughhistonehyperacetylation,DNAhypomethylationandthemodulationofseveraltranscriptionfactors,whichmayplayanimportantroleinneuraltubeclosureinsensitivepatientsviamediatingthegeneexpression.Inthis lecture,wewillanalysetheroleofgeneticpolymorphismsoffolatematabolicenzymes,andDNAmethylationandinhibitionofhistonedeacetylases(HDACs)inNTDsinducedbyVPA,andexplorethemechanismofNTDscausedbyVPA.


Ketogenic Diet / Modified Atkins Diet for Epilepsy

Phyllis YP Yau1, Eva LW Fung2

1 Dietetics Department and 2 Department of Paediatrics, Prince of Wales Hospital, Hong Kong SAR

Ketogenicdiethasbeenusedfortreatingepilepsyforalmost100years.Theutilisationandinterestsinthedietanditsmodification/variationareincreasinginthepastdecade.Withmoreclinicalexperienceandscientificdocumentationofitsefficacy,itsuseshavealsobeenincludedinlatestNICEguidelines.Therearealsoreportsofimplementingthedietintheacutesetting,especiallyincaseswithsuper-refractorystatusepilepticus.Someofthegreatesthurdlesinimplementingtheketogenicdietaretherestrictioninfoodintake,labour-intensiveimplementation,andmaintenanceofthedietandconcernsontheoreticalhealthrisksassociatedwiththediet.Thedevelopmentof less‘stringent’alternatives, likemodifiedAtkinsdietandlowglycaemicindexdiet,havebecomemuchmoreattractive,especiallyforadults.Theyaremucheasiertoimplementandmaintain,bothforthepatientsandclinicians/dietitians.Thereisnorestrictioninmealtimes,calories,andliquid,etc.Studieshavealsodemonstratedtheefficacyinbothchildrenandadults.Besidesusesinepilepsies,newapplicationsofketogenicdiettherapiesforothermedicalconditionshavealsobeenexplored,includingamyotrophiclateralsclerosis,diabeticneuropathy,andmalignantbraintumours,etc.

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Management of Gait Disorders in Parkinson’s Disease: a Neurologist’s Perspective

Germaine HF ChanDepartment of Medicine, Queen Elizabeth Hospital, Hong Kong SAR

Gaitandbalancedisorderisacommon,yetdebilitatingprobleminParkinson’sdisease(PD)patients.TheSydneymulticentrestudyshowedahighfallriskof87%inadvancedPDpatients,resultinginfracturesandimmobilisation.ArecentlypublishedChinesestudyalsoreproducedsimilarresults.Therefore,it is importanttounderstandthepathophysiologicalmechanism,detecttheriskfactors,andprovideappropriatetreatment.

Pathophysiological mechanism of gait and balance disorders in Parkinson’s disease GaitandbalancedysfunctioncanoccurinanystagesofPD,eventhoughitismorecommoninadvancedPDpatients. InearlyPD,dopaminedeficiencyaccounts for theseaxialsymptoms.Nonetheless, inadvancedPD,gaitdisorderismorecomplexandis likelytoinvolveboththedopaminergicandnon-dopaminergicpathways.Besides,difficultyinmulti-tasking,impairedsensorimotorintegration,aswellasalackofcompensatorystepping,maycontributetoahigherincidenceoffallsinPDpatients.

Risk factors of falls in Parkinson’s diseaseAhistoryoftwoormorefallsinthepreviousyearisfoundtobethebestpredictivefactoroffallsinPDpatients.Impairedambulation,poorlowerlimbmotorplanning,andorthostasisalsopredictgaitandbalanceproblems.

Management of gait and balance disorders in Parkinson’s diseaseAxialsymptomsinparkinsonismcanbedividedintotwogroups:dopamineresponsiveanddopamineresistant.InearlyPDpatients,whendopaminedeficiencyisresponsibleforthesesymptoms,steppingupdopaminergicmedications is thesolution. InadvancedPDpatients, thegaitdisordersaremorecomplicatedandareoftenrefractorytodopaminergictreatment.Inthiscase,drugstargetingonthenon-dopaminergicsystem,suchasmethylphenidateandamantadine,maybeusefultoimprovethegaitandbalanceissues.

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The Therapeutic Effect of Hepcidin in Parkinson’s Disease Via Regulation of Brain Iron and α-Synuclein Accumulation

Ya KeSchool of Biomedical Sciences, Faculty of Medicine and Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR

Experimental andclinicalevidencesuggest that abnormal ironaccumulation is involved in thepathogenesisofParkinson’sdisease(PD).Sincethehormonehepcidinisthemainregulatorofbodyiron level, includingthat inthebrain,wehypothesisethathepcidinoffers therapeuticpotential inParkinsonism.WetestedourhypothesisbasedonaratmodelofPDviachronicinjectionofrotenone.InthismodelthatcapturestheclinicalfeaturesofPDwithrespecttoα-synucleinaccumulationaswellastheprogressivenatureofthedisorder,wefoundthatchronicrotenonetreatmentresultedinselectiveaccumulationofα-synucleinandironinthesubstantianigraparscompacta,whichwasaccompaniedbydegenerationofdopamineneurons.Themotorability,assessedbytheopenfieldtestandgridtest,wasalsosignificantlyreduced.Injectionoftheadenovirus-hepcidinstartingonday5intothelateralcerebralventriclecouldsignificantlyrescuethemotordeficit inducedbyrotenone.Postmortemexaminationandin-vitroexperimentsrevealedthattheover-expressedhepcidincouldsuppressα-synucleinandironaccumulation,andreducedneuronaltoxicity.Together,theseresultsstronglysuggestthatmanipulatingthelevelofthehepcidincouldbeapromisingtherapeuticstrategyforPD. ThisworkwassupportedbytheNational973Program(2011CB510004);CUHKDirectGrant(4054042).

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Rehabilitation of Gait Disorders in Parkinson’s Disease

Margaret MakDepartment of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong SAR

WalkingdifficultyisoneofthecardinalsignsleadingtodisabilitiesinpeoplewithParkinson’sdisease(PD).PDpatientsmanifestcontinuousgaitimpairmentsuchasreducedstridelength,reducedgaitspeed,andincreasedstridetimevariabilityand/orepisodicgaitdisorderssuchasfreezingofgait,whichpredisposethemtofalls.Infact,walkingisthemostcommonfall-relatedactivityamongPDpatients.Physiotherapistsplayanimportantroleintherehabilitationofwalkingwhichincludesbothevaluationandtreatment.Gaitassessmentiscarriedouttounderstandthebiomechanicalmechanismsunderlyinggaitdisorderssoastodesignappropriatetreatmentstrategiesaswellastoevaluatetreatmentoutcomes.Numerousstudieshavefoundthattheuseofexternalcuesresults inimmediateimprovementofstridelength,walkingspeed,andwalkingpattern.Thesecuesincludeauditorycues,visualcues,tactilecues,orcognitivecues.Therearepreliminaryreportsonthebenefitsofexternalcuesonenhancingdualcognitive-walkingandturningtasks.Inadditiontocuedtraining,gaittrainingonatreadmillhasbeenfoundtoincreasewalkingspeedandreducevariabilityofgaitandfreezingofgait.Recentstudiesreportedtheeffectsofnon-invasivebrainstimulationtechniquessuchasrepetitivetranscranialmagneticstimulationonenhancingwalkingperformance inPDpatients.Researchevidenceon theseapproachesand theproposedmechanismswillbepresented.

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Mechanism of Deep Brain Stimulation in Parkinsonism: Direct Involvement of the Primary Motor Cortex

WH Yung School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR

High-frequencydeepbrainstimulation(DBS)appliedtothesubthalamicnucleus(STN)hasprovedtobeusefulintreatingParkinson’sdisease(PD),butitsmechanismremainsenigmatic.Inprinciple,DBScandirectlyactivateawiderangeofneuronalelementsinthetargetandsurroundingareas,includingneuronalsoma,nerveterminalsandaxonsofpassage.WehypothesisethatabnormalactivitiesintheprimarymotorcortexplayacriticalroleinthemanifestationofPDsymptomsandcouldbeatargetofDBS.ToenableustoaddressthisquestiononananimalmodelofPD,wemaderecordingsofbothsingle-unitactivitiesandlocalfieldpotentialsinthemotorcortexoffreelymovinghemi-Parkinsonianratsbefore,during,andafterSTN-DBS.Inthesemovement-disabledanimals,abnormalbetarhythminthemotorcortexwasfound,whichwasaccompaniedbymarkedincreaseinburstfiringandsynchronyamong layerVmotorcorticalprojectionneurons.During thedeliveryofSTN-DBS,we identifiedshort-latencyantidromicspikesinlayerVneurons.Intriguingly, increasedfailureratewithincreasingstimulationfrequencyproducedthehighestnumberofrandomantidromicspikesat125Hzstimulation,whichcorrelatedwiththeoptimaltherapeuticefficacyontheseanimals.Thiseffectwasaccompaniedbyincreasedfiringrate,reducedburstspikingandsynchronyoffiringinthemotorcorticalneurons.Fieldpotentialanalysisrevealednormalisationofthepathologicalbetarhythm.Importantly,wefoundevidencethatthefiringprobabilityofthecorticalprojectionneuronwasmodifiedfollowingtheoccurrenceofanantidromicspikesuggestingthatdirectinterferenceofsynchronisedfiringbystochasticantidromicspikesunderliesthebeneficialeffect.OurresultsthereforesupportthatSTN-DBSantidromicallyactivatesoutputneuronsinthemotorcortexthroughthecorticosubthalamicnucleusprojection,whichdirectlydisruptsabnormalneuralactivitiesinthemotorcortexinPD.Althoughdirectstimulationofthemotorcortexinpatientsisstillcontroversial,ourresultshighlightthatgivenasuitablestimulationparadigm,themotorcortexcouldbeapotentialtargetforthetreatmentofPD.

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Spinocerebellar Ataxia in Chinese

Anne YY Chan1, Edwin HY Chan2

1 Department of Medicine and Geriatrics, Prince of Wales Hospital, Hong Kong SAR2 School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Hong Kong SAR

Spinocerebellarataxias (SCA)1,2,3and6are themostcommonautosomaldominantly inheritedcerebellardegenerations.IntheChinesepopulation,themostcommonSCAisSCA3andthefrequencyofSCA3amongSCApatientsis72.5%,followedbySCA2withthefrequencyof12%amongSCApatients.ForSCA1,thefrequencyamongSCApatientsis7%.EventhoughSCAsarerarediseases,asignificantnumberofChinese inHongKongstillsufferfromthisdisorder.HongKongSpinocerebellarAtaxiaAssociationhas88memberswhoaresufferingfromcerebellardegeneration,manyofthemhaveageneticconfirmation. AstherearefewtreatmentsforSCA,understandingitsclinicalmanifestationanddiseasemechanismsisthefirststeptowardsdevelopmentofeffectivetreatment.InEuropeandNorthAmerica,twolargestSCAconsortiainvolvingmanymedicalcentres,EuropeanSCAgroup(EUROSCA),andClinicalResearchConsortiumforSpinocerebellarAtaxias(CRC-SCA)haveestablishedbio-repositorybankstocollectSCApatients’clinicalandgeneticinformationaswellasthenaturalhistoryofSCAs.FromthenaturalhistorystudiesofSCA1,2,3,6,and7,ofthesetwoconsortia, theyalsodevelopedScalefortheAssessmentandRatingofAtaxia(SARA),whichisavalidatedclinicaltooltoreliablyquantifythedegreeofataxiasymptoms.However,wedonothaveacentralisedataxiacentrecollectingsuch informationandspecimeninHongKong.EstablishinganataxiaregistryforclinicalandgeneticinformationinHongKongwillfacilitatetheataxiaresearchworldwide. Spinocerebellarataxias (SCAs)areagroupofgeneticallydiverseneurodegenerativedisorderscausingcerebellardegenerationandprogressiveataxia.Therearecurrently36typesofSCAreportedbutonly21disease-causinggenes/mutationshavebeendetermined.IdentifyingtheunderlyingmutationsenablesmechanisticinvestigationofpathogenesisandsubsequenttherapeuticdevelopmentofSCAs.Byperformingexomeandwhole-genomesequencingonmultiplefamilymembersofanautosomaldominantSCAfamily,weidentifiedasingle-pointmutationinthecodingregionofaprotein-codinggeneinallaffectedindividuals.Further,thismutationwasnotobservedinover200controlgenomescollectedinthelocalpopulation.Clinically, thepatientsexhibitedtypicalcerebellarataxiasignsandmagneticresonanceimagingshowedobviouspontocerebellaratrophyalongwithaglobalreductioninbrainvolume.SincenoknownSCAhaspreviouslybeenassignedtothegeneticlocusoftheidentifiedmutation,ourstudyunveiledanovel formofautosomaldominanttypeofSCAandwenamedthisconditionSCA37.

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Identification and Characterisation of a Cognitive Enhancer from Traditional Chinese Medicine

Fanny CF Ip, Nancy Y IpState Key Laboratory of Molecular Neuroscience, Division of Life Science, The Hong Kong University of Science & Technology, Hong Kong SAR

Neurodegenerativediseases,characterisedbyprogressivelossofneurons,areemergingtobecomeamajorhealthburdeninsocietieswithalargeageingpopulation.Increasingevidencesuggeststhatsynapticdysfunctionplaysakeyroleintheonsetandprogressionofneurodegenerativediseases.Tothisend,wehaveleveragedourresearchstrengthsinmolecularneuroscienceandChinesemedicinetoestablishafocuseddrugdiscoveryprogrammeinsearchofnoveldrugleads,includingthosethatcanregulatesynapticactivity.Wereportherethediscoveryofamultivalentherb-derivedcompound,whichmodulatesfunctionoftheAMPA-typeofglutamatereceptorbyincreasingserinephosphorylationofAMPAreceptorsubunitGluA1,whichisimportantfortraffickingGluA1-containingAMPAreceptorstothesynapses.Administrationofthiscompoundactivatesanarrayofsignallingpathwaysthatarecriticalforsynapticplasticity, resulting in increasedproteinexpressionof theneurotrophinbrain-derivedneurotrophic factorandenhanced levelofmonoamineneurotransmitters inmousehippocampus.Furthermore, thiscompoundcan rescue impaired long-termpotentiation inbrain sliceseithertreatedwithamyloid-betaoligomersor isolated fromTg2576Alzheimer’sdiseasemouse. Invivo,thiscompoundenhancesthereferencememoryofmiceintheMorriswatermazetask,reducesthedurationof immobility intheforcedswimtest,andrescuesneurologicaldeficits inastrokemodel.Theseobservationssuggestthatthiscompoundisanattractivecandidatefordevelopmentasacognitiveenhancertoalleviatememorydysfunctionsassociatedwithageingandneurodegenerativediseases. ThestudyissupportedinpartbyNationalBasicResearchProgramofChina(973Program),ShenzhenPeacockPlan,theHongKongResearchGrantsCouncilTheme-basedResearchScheme(T13-607/12R),andInnovationandTechnologyFund[StateKeyLaboratory(ITCPT/17-9)].

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Individualised Stem Cell Therapy

Ken KL YungDepartment of Biology, Hong Kong Baptist University, Hong Kong SAR

NeurodegenerativediseasesincludingAlzheimer’sandParkinson’sdiseasescancripplelivestovaryingdegrees: fromminordisability to lossofmovementormemory.Atpresent, thereareonly limitedtherapiesforneurodegenerativediseases.Researchinneuralstemcellandregenerativemedicineusingfunctionalneuralstemcellsfromadulthumanbrainiscurrentlyhinderedduetoriskswithbrainsurgeryandtheuncertaintyinthelocationofextraction.Herein,wehaveadoptedlatestinterdisciplinarydesignsandthencombinethenovelnanomaterials todevelopan innovativetreatment.Wedemonstrateasimplemagneticseparationmethodforthesingle-stepextractionofstem/progenitorcellsfromchoroidplexus liningalongthesubventricularzonebyapplyingantibodies-conjugatedmagnetic ironoxidenanoparticles(Ab-MNPs)tothecorrespondingregioninaratbrainwithasuperfinemicro-syringe.Itisshownthatthemagneticallyisolatedbutactivestemcellscanbedevelopedintoneurospheresanddifferentiatedintodifferenttypesofcells inculturemediumin-vitrooutsidethesubjectbody.Thisuniquecharacteristicleadsustodevelopanewtailor-madeneurologicaldisordertherapyasthecellscanbeextracted,modified,andre-appliedtothesamesubject.Asthecellsareoriginatedfromthepatientsthemselves,theriskofimmunerejectioncanbegreatlyreduced.Webelievethatthismethodcouldbeadoptedableasanewtailor-madestemcelltherapybyharvesting,engineering,anddosingtoindividualpatients’ownneuralstemcellsforneurologicaltreatments. Angewandte Chemie International (DOI:10.1002/anie.201305482)

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Intracranial Abscesses and Infections of Neurosurgical Shunts and Drains

YW FanPrivate practice, Hong Kong SAR

Anoverviewofmanagementofintracranialsuppurativeinfectionandcerebrospinalfluid(CSF)shuntcatheterinfectionispresented. Intracranialsuppurativeinfectionsarelife-threateningbuteminentlytreatableconditions.Lackingthealertnessofsuchconditioncan leadtodelay indiagnosisandtreatment.Theclinical features,imagingfinding,roleofsurgery,andantibioticstreatmentstrategiesinthemanagementofintracranialsuppurativeinfectionarediscussed.Withtheincreasingpopularityofendovascularintervention,weareseeingmoreandmoreintracranialinfectivecomplicationsrelatedtoindwellingdevicesandintra-arterialadministrationofmedication.Illustrativecasesarepresented. ThesecondpartofthepresentationisrelatedtoCSFshuntcatheterinfection.AlthoughCSFshuntinghasbeenremarkedasthemostsuccessfulinventioninthehistoryofneurosurgery,neurosurgeonsaretryinghardtoavoidputtinginshuntsintheirpatientsnowadays.ShuntcatheterinfectionisthemostcommoncomplicationinCSFshuntingoperation.Aetiologicalfactors,waystoavoidcatheterinfection,diagnosis,andmanagementofshuntinfectionarediscussed.IndicationsofprophylacticantibioticsforpatientswithCSFshuntgoingfordentalprocedures,gastrostomy,andlaparotomyarediscussed.

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Treatment of Refractory Multiple Sclerosis

Finn SellebjergDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

Treatmentwithinterferon-betaorglatirameracetatehasbeeninroutineuseforthetreatmentofclinicallyisolatedsyndromesandrelapsing-remittingmultiplesclerosis(RRMS)foralmosttwodecades.Althoughmanypatients remainclinicallyandradiologicallystableon treatment,otherpatientshaveeitherradiologicalevidenceofongoingdiseaseactivity,continuetohaverelapses,ordevelopaprogressivediseasecourse.Whethersuchpatientsshouldbeconsiderednon-responsive,ierefractorytotreatment,ortomerelyhaveaninsufficientresponseremainsamatterofdebate. Someoftheemergingoraltherapies,egdimethylfumarate,laquinimodandteriflunomidehavebeencomparedtothewell-known,injectablefirst-linetherapiesinrandomisedcontrolledtrialswithoutclearevidenceofsignificantdifferencesinclinicalefficacy. For patients with high disease activity treatment immunosuppression with mitoxantrone orcyclophosphamidehasbeenusedinsomecountries,andmaystillbeanoptionforpatientsconvertingtoasecondaryprogressivediseasecourse,althoughtoxicitylimitsthegeneraluseofthesetreatments.Natalizumabiswidelyusedasasecond-linetreatmentforRRMS,buthasneverbeencomparedtoothertreatmentsinphase3trials.Fingolimodtreatmentwassuperiortointerferon-beta1ainoneclinicaltrial.Insomecountriesfingolimodislicensedasafirst-linetherapy,inothercountriesonlyforpatientswithhighdiseaseactivityorasasecond-linetherapy.Mostrecently,lymphocytedepletionwithalemtuzumabwasshowntobesuperiortointerferonbeta-1bothasfirst-lineandsecond-linetherapy. Thechoiceoftreatmentfortheindividualpatientwithaninsufficienttreatmentresponsewilldependonathoroughevaluationofthepreviousdiseasecourse,treatmenthistory,thepresenceofriskfactorsforsevereside-effectsoftherapy,andtheevidenceofefficacyforthetreatmentoptionsconsidered.

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The ‘Not So Common’ Causes of Central Nervous System Infection in Hong Kong: Diagnoses You Cannot Afford to Miss

Jasper FW ChanDepartment of Microbiology, Li Ka Shing Faculty of Medcine, The University of Hong Kong, Hong Kong SAR

Infectionofthecentralnervoussystemisaninfectiousdiseaseemergencyfrequentlyencounteredbytheneurologistsinclinicalpractice.Earlydiagnosisandtreatmentisessentialinreducingthesignificantmorbidityandmortalityassociatedwiththeseinfections.Unfortunately,uptotwothirdsofencephalitiscasesanda largenumberofchronicorpartiallytreatedacutemeningitiscasesremainofunknownaetiologydespiteanextensivediagnosticworkup.InametropolitancitywithahighstandardofhealthcarelikeHongKong,mostphysiciansarecompetentinmanagingpatientswithcentralnervoussysteminfectionscausedbycommonpathogenswithestablisheddiagnosticalgorithmsandtreatmentstrategies.However,casescausedbyunusualpathogensorthosewithatypicalmanifestationsoftencausediagnosticdilemmas,andhence,delayintreatment.Anindividualisedclinicalmanagementapproachwithaspecificfocusonepidemiologicalriskassessmentandcloseliaisonwiththeclinicalmicrobiologylaboratoryforstate-of-the-artdiagnostictestsareessentialindecipheringthesecretsofinfectionscausedbythese‘notsocommon’bugs.

Ten Minutes Vestibular Examinations but Persistent Rehabilitative Exercises

Dennis KK AuDepartment of Surgery, Li Ka Shing Faculty of Medcine, The University of Hong Kong, Hong Kong SAR

Vertigo isacommon illness thatpatientsseekconsultation inENTclinics.Patientsoftenhaveahallucinationofenvironmental rotationwhilepatientswithdizzinessoftenhaveasenseof light-headedness.Thispresentationwill introducesomeusefulbutsuccinctclinicalexaminations thatmedicalpractitionerscandoinabout10minutestomakeinitialdiagnosiswhetherthevertigohasaperipheralorcentralcausebeforereferringthepatientformoresophisticatedvertigoandvestibularassessments.Somelatesttechnologiesinassessingvestibularfunctionsarealsointroduced.Vestibularordizzyrehabilitativeexerciseshouldfollowifpermanentvestibularparesisisfound.Withunilateralvestibularlesions,asymmetryoftonicvestibulospinalactivitymayleadtoposturalandgaitimbalance.With symmetrical vestibular loss, the imbalancewillbemorepronouncedandpersistent.Thispresentationintroducessomevestibularordizzinessexercisesthatcanbepractisedbythepatientsathome.Theseexercisestrytoprovokeimbalanceanddizzinessbutatthesametimetrytoimprovethebraintocompensateforanyabnormalitiesinthevestibularsystemandtoretrainthebraintoadaptandtoleratetheinformationfromthedeficitvestibularapparatus.Theexercisesalsotrainthevisualandsomatosensorysystemstocompensateandassistinbalancingandreducethesenseofdizziness.


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S 18

Neurostimulation in Primary Headache Disorders

Raymond CK ChanDepartment of Medicine, United Christian Hospital, Hong Kong SAR

Primaryheadachesarecommonneurologicalproblemsandareasocioeconomicburden.Thequalityoflifecanbeseverelyjeopardisedifthepainisnotadequatelycontrolled.Thechronicforms,chronicdailyheadache,arethemostdisablingandareusuallyrefractorytomedications.Primarychronicdailyheadachescanbeduetochronictension-typeheadache(CTTH),chronicmigraine(CM),newdailypersistentheadache(NDPH),chronicclusterheadache(CCH),chronicparoxysmalhemicrania(CPH),short-lastingunilateralneuralgiformheadacheattackswithconjunctivalinjectionandtearing(SUNCT),short-lastingunilateralneuralgiformheadacheattackswithautonomicsymptoms(SUNA)andhemicraniacontinua(HC). Neurostimulation isrecentlyemergingasanovel treatmentmodality forpatientswithchronic,disabling, and drug-refractory primary headache disorders. Central neurostimulation methodsincludedeep-brainstimulation(DBS)andtranscranialmagneticstimulation(TMS)whereasperipheralneurostimulationmodalitiesincludeoccipitalnervestimulation(ONS),vagusnervestimulation(VNS),sphenopalatineganglionstimulation (SPS),auriculotemporalnervestimulationandsupraorbitalnervestimulation.ThepreliminaryresultsofDBSandONSarepromising.Currentlytherearemorethan60patientswithdrug-resistantclusterheadache(CH)implantedwithDBSwith64%successrateinpainreduction.TherationaleofDBSinCHstemsfromthefindingofhyperactivationofposteriorhypothalamus in the functional imagingduringheadacheattack.ForONS, itsefficacy in treatingheadachepainwasfirstobservedfromitssuccessfultreatmentindrug-resistantoccipitalneuralgiaandsofarthereareabout500CMand90CHpatientstreatedbyONSwithpainimprovementrateof56%and67%,respectively.Intheongoingrandomisedcontrolledtrial,theONSTIMtrial,thepreliminaryresultssuggestthatONSismoreeffectivethanplaceboormedicaltherapyinmedically intractablechronicmigraine. Insummary,ONSandDBSofposteriorhypothalamusseemtobeeffectiveinCCH,andONSseemstobeapromisingtreatmentinCM.Moredatafromfurtherrandomisedcontrolledtrialareneededtoconfirmtheirefficacy.

Late-onset Pompe Disease in the New Enzyme Replacement Therapy Era

Bun ShengDepartment of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong SAR

Pompedisease(PD)isanautosomalrecessivedisordercausedbythedeficiencyoflysosomalenzymeacidα-glucosidase(GAA).Thediseasehastwoclinicalforms.Theclassicinfantileformdevelopsseverehypotoniaandhypertrophiccardiomyopathyshortlyafterbirth.Untilenzymereplacementtherapy(ERT)becomesavailable,victimsofthisdevastatingformseldomsurvivebeyondtheirsecondbirthday.Late-onsetPD(LOPD)ismoreheterogeneous.Patientsusuallypresentwitha limbgirdlepatternofmuscleweaknessanddeveloprespiratoryimpairmentearlyon,buttheheartisalmostalwaysspared.TheclinicalformandseverityofthephenotypeiscorrelatedtotheamountofresidueGAAactivity,whichisdeterminedbythemutations. Inacompoundheterozygousmutation, ifoneallelecarriesaseveremutation,egframeshift, theresultedphenotypewillbeasevereone.Unfortunately, thecommonmutationinChineseisasevereone;ourLOPDpatientsoftenhaveseverephenotype,withearliersymptompresentation,respiratoryfailure,andrequirementofassistedventilation.ERTwithalglucosidase-α (myozyme)wasfirst licensedbyFoodandDrugAdministrationin2006fortreatmentofinfantilePD,andthedrugwasavailableinHongKongsince2008.FollowingthepublicationonthefirstrandomisedtrialofmyozymeinLOPDin2010,HongKongstartedthefirstERTontwobrothersinDecember2010.TherearenowfiveLOPDpatientsonERT.FourpatientshadERTformorethan1year,allshowedimprovementorstabilisationoftheirrespiratoryfunctionandmobility,theoverallresponsewascomparableorevenbetter thanthat intheclinical trials.Nevertheless, thesepatientshaveanaggressivephenotype;theirclinicalcourseisdifferentfromthesubjectsinclinicaltrials.Itisstilltooearlytoconcludewhethertheseearlybenefitscouldbesustainableovertime.ERTnotonlybringsthefirsteffectivetreatmentinLOPD,italsomagnifiesthebenefitofadjuvanttherapiesincludingnutritionandexercise,whichonlyprovidetransientorshort-termeffectsinthepre-ERTera.NewstrategiestoimprovetheefficacyofERTison-going;bettertissuedelivery,autophagytargeted,biologicchaperones,andtheuseofβ2agonistalbuteroltoboosttheleanmuscleareamongthemanyfancyideas.Manyquestionsawaitanswersandmanyproblemsareunsettled,butabetterfutureispromisedinLOPD.


Experience of Using Intravenous Thrombolysis in Elderly Patients with Major Acute Ischaemic Stroke in Kwong Wah Hospital

Helen Yip, MC Kwan, WK Cheng, WY Lau, KF Ko, TY Chan, ML LaiDepartment of Medicine and Geriatrics, Kwong Wah Hospital, Hong Kong SAR

Elderlypatientswithmajorischaemicstrokesmayremainseverelyhandicappedordead.Wereportedtwoelderlypatientsagedgreaterthan80yearsatthetimeofintravenousthrombolysistreatmentgivenin2009to2010. An84-year-oldman(patient1)withahistoryofparoxysmalatrialfibrillationwasadmittedtoKwongWahHospitalinMarch2010forcongestiveheartfailure.HedevelopedacuterighthemiplegiaduringhospitalisationwithNIHSS26.Urgentcomputedtomography(CT)of thebrainwasunremarkable.Intravenousthrombolysiswascommencedafterevaluation.Follow-upNIHSS1daylaterwas13.CTfollowingthenextdayrevealedaninfarctinanteriorpartofleftmiddlecerebralarteryterritory.Therewasnosignofhaemorrhagictransformation.Strokeriskfactorswerebeingoptimised.Hewasabletowalkwithstickundersupervisionwithresidualexpressivedysphasiaafteracourseofrehabilitation.ImprovementofBarthelIndex(BI)from0to79wasreportedafter3monthsoftraining. Another83-year-oldwoman(patient2)wasable towalkunaidedprior toadmission.Shehadahistoryofhypertensionandwasadmittedinyear2009forhyperacutestrokepresentedwithdenserighthemiplegiauponadmissionwithNIHSS15.UrgentCTofbrainwasunremarkable.Shewastreatedwithintravenousthrombolysiswithgoodneurologicalrecovery.Thepatientwasdischargedtorehabilitativecareonday8.At3-monthfollow-up,shewasabletowalkwithstickwithgoodachievementinBIscorefrom48to90afterrehabilitation. Acutethrombolysistherapyisaneffectivetreatmentforacuteischaemicstroke.However,elderlypatientshavemostlybeenexcludedfromacuterevascularisationtrials,duetopoorprognosisasaresultofconcurrentmedicalillness,andfearofhaemorrhagiceventsfromthesetreatment. Theabovetwocasesshowedthatthrombolysisbenefitselderlystrokepatients.ImprovementinBIwascontemplatedinthesetwopatients.Incarefullyselectedpatientswhomeeteligibilitycriteriaforthrombolysis,treatmentshouldnotbewithheldonthebasisofagealone.

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Griffiths Mental Developmental Scales Validation for Chinese Children

Winnie WY Tso1, LI Ao2, M Li3, X Zhang4, FY Jiao5, X Xu6, KX Du7, XL Xia8, Denise Challis9, Virginia CN Wong1

1 Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong SAR2 Rehabilitation Medicine, The Second Affiliated Hospital of Kunming Medical University, PR China 3 Child Neuro-Habilitation Clinic, Department of Paediatrics, The First Hospital of Peking University, PR China4 Department of Child and Adolescent Health, Vice-Dean of School of Public Health, Tianjin Medical University, PR China5 Department of Paediatrics, Shaanxi Provincial People’s Hospital of Xi’an Medical University, PR China6 Child Health Care Department, The Paediatric Hospital of FuDan University, Shanghai, PR China7 Department of Child Neurology, The Third Affiliated Hospital of ZhengZhou University, PR China8 The Second Affiliated Hospital of Kunming Medical University, PR China9 Research and Re-standardisation Committee, The Association for Research in Infant and Child Development

Background:TheGriffithsMentalDevelopmentalScales(GMDS)havebeenusedextensivelybydoctorsandpsychologists inmanycountriestoassessachild’sdevelopmentalprofile. InChina, there isanincreasingawarenessofdevelopmentaldisordersinchildren;theprevalenceofpreschoolchildrenwithdevelopmentaldisorderswasreportedtobeashighas12.97%.TheGMDShavebeendevisedbasedonobservationoftheperformanceofchildrenlivingintheWest.However,thereareobviousdifferencesinthecultureandbeliefsofpeoplegrowingupinAsiaascomparedtothoselivinginwesternsocieties.Inthisstudy,theGMDShavebeentranslatedintoChineseandmodifiedaccordingtoChineseculture.ThisprospectivestudyaimedtoprovidevalidationoftheGMDSforChinesechildren.Methods:ChinesechildrenfromsevendifferentcitiesinChinawithapparentlynormaldevelopmentwithnosignificantmedicalhistorywererecruitedintothestudy.TheirdevelopmentswereassessedusingtheGMDS.Results:GMDSscoreswerecollectedandanalysedforatotalof815Chinesechildrenwithagesrangingfrom1monthto8yearsold;391(48%)werefemale.Smooth‘developmentalgrowth’chartsandstandarddeviation/percentilescoreswerecomputedforeachoftheneurologicaldevelopmentalscalesusingtheLMSmethod.Plotsofthe1st,2.5th,5th,10th,25th,50th,75th,90th,95th,97.5th,and99thpercentileswillbepresentedforeachofthesixsub-scalesandtheoverallGriffithsscore.Conclusion:TherearedifferencesintheChinesedevelopmentalpercentilecurvesascomparedtotheBritishdevelopmentalpercentilecurves.ThesedifferencesaremostobviousinsubscaleF.ChinesechildrenshouldbeassessedusingourvalidatedChinese‘developmentalgrowth’charts.Thiswillpreventunder-estimatingorover-estimatingthedevelopmentalmilestonesinChinesechildren.

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The Prognosis of Acute Symptomatic Seizures after Ischaemic Stroke

T Leung, H Leung, Y Soo, C Leung, V Mok, KS WongDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR

Background and purpose:Seizureisanimportantco-morbidityofstroke.Thisstudyinvestigatedthecharacteristics/prognosisofpatientswithacutesymptomaticseizure(AS)(early,<7daysofstroke)afterischaemicstroke(IS).TheseoutcomemeasuresareimportantwhenconsideringcontroversialtreatmentoptionsinpatientswithconcurrentIS/AS.Methods:Weprospectively investigated2925ISpatients fromapopulation-basedacutestrokeunit(ASU).Thestroke-relatedparameterswereage/sex,strokeaetiology,strokeseverity,functionaldisability,transient-completeocclusion,orpartial recanalisation,multiple-territory infarctandhaemorrhagictransformation.Theseizure-relatedparameterswere(1)ASco-occurringwithincidentIS(CS,day2-7afterstroke),(2)ASfollowingtherecurrenceofIS(ASS>7daysafterincidentstrokewithanotherIS/AS),(3)remotesymptomaticseizure(US,>7daysafterincidentstrokewithoutIS).Weexcludedpatientswithintracerebralhaemorrhage,subduralhaematoma,subarachnoidhaemorrhage,orvenousinfarcts.Results:TheincidenceofASinISwas3.9%(115/2925).Atotalof104patientswithAS/IS(meanage,65years;55%female)hadameanNationalInstituteofStrokeScale(NIHSS)scoreof11.Cardio-embolismwasfoundin48.1%(50/104)andtransient-completeocclusion/partialrecanalisationin30.8%(32/104).Haemorrhagictransformationwasonlyfoundin16.4%(17/104).ThecombinedriskofCS+ASSwas28%at1year,30%at2yearsand40%at8years.TheriskofdevelopingUSwas28%at8years.Statusepilepticus,presenceofanotheracutesymptomaticcause,>2cardiovascularriskfactorswerepredictiveofCS+ASS(P<0.05)andepileptiformdischargeonelectroencephalogram(EEG)forUS(P=0.04).SubgroupanalysisofAS/ISwithseizure-at-onsetdidnotdifferintheircharacteristicsorprognosticindicators.Conclusions:Whilethelong-termriskofdevelopingepilepsyafterIS/ASwasonly28%,additionalacutesymptomaticseizuresarefoundwith indexstrokeorduringrecurrentstrokes inanother40%.Thishas implicationsforshort–to–mediumtermantiepilepticdrugtreatment.Theprognosis intermsofhaemorrhagictransformationinpatientspresentingwithischaemicstrokeandseizureatonsetwithoutthrombolysisbeinggivenwas16%.

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AUTHOR INDEXPageNo.

A

LIAo 28

DKKAu 26

C

DChallis 28

AYYChan 23

EHYChan 23

GHFChan 20

JFWChan 26

RCKChan 27

TYChan 28

ZYChen 19

PWCheng 17

WKCheng 11,28

D

KXDu 28

F

YWFan 25

MKFong 14

CWFung 13

ELWFung 20

H

ACCHo 13

LFHui 10

I

FCFIp 24

MFIp 12

NYIp 24

J

FYJiao 28

K

YKe 21

KFKo 11,28

MCKwan 11,28

CMKwok 10

AKYKwong 13

L

MLLai 28

WYLau 11,28

CLeung 29

EYCLeung 16

HLeung 29

TLeung 29

MLi 28

SHLi 12

HTLui 10

WMLui 18

M

KKMa 12,15

MMak 21

VMok 29

S

FSellebjerg 25

BSheng 27

YSoo 29

T

WWYTso 28

W

TYWai 12

AHYWong 14

KSWong 29

PageNo.


PageNo.

KYWong 10

PTYWong 9

VCNWong 9,13,28

X

XLXia 28

XXu 28

Y

PYPYau 20

HYip 11,28

KKLYung 24

WHYung 22

Z

XZhang 28

LMZhou 19


Acknowledgements

TheOrganisingCommitteewouldliketoextendtheirgratitudetothefollowing

sponsors(inalphabeticalorder)fortheircontinuingsupport:

AllerganHKLtd

BayerHealthCareLtd

BiogenIdec(HK)Ltd

Boehringer-IngelheimHKLtd

Eisai(HK)CoLtd

EVERNeuroPharma(Asia)Ltd

Genzyme–ASanofiCompany

GlaxoSmithKlineLtd

IPSENPharma(HK)

JanssenPharmaceuticaHongKong

LundbeckHongKong

MedtronicInternationalLtd

MerckPharmaceuticalHKLtd

MerckSharp&Dohme(Asia)Limited

NovartisPharmaceuticals(HK)Ltd

OrientEuropharmaCoLtd

OtsukaPharmaceutical(HK)Ltd

PfizerCorporationHKLtd

Lastbutnotleast,wewouldliketothankallspeakers,chairmen,presentersand

participantsfortheirparticipationandcontribution.

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