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Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011 1
2nd Hong Kong Neurological Congress cum24th Annual Scientific Meeting of The Hong Kong Neurological Society
Council of The Hong Kong Neurological Society 5
Organising Committee 5
List of Speakers 6
Scientific Programme 7
SESSION ABSTRACT PAGE
FREE PAPER PRESENTATIONS3D Rotational Angiography as a Screening Imaging Test FP 1 10for Intracranial StentingFlorence SY Fan
Intravenous Alteplase for Ischaemic Stroke Patients with FP 2 10Borderline Eligibility in Hong Kong—How Selective Should We Be? Alexander Lau, Edward Wong, Yannie Soo, Deyond Siu, Venus Hui, Edward Shum, Cecilia Leung, Colin Graham, Thomas Leung, Lawrence Wong
Subthalamic Deep Brain Stimulation for Advanced FP 3 11Parkinson’s Disease: Efficacy and ComplicationsMovement Disorder Group, Prince of Wales Hospital, The Chinese University of Hong Kong; Anne Chan, Jonas HM Yeung, Danny TM Chan, XL Zhu, Edith Wong, KY Lau, Rosanna Wong, Christine Lau, Vincent CT Mok, Wayne WS Poon
Guillain-Barré Syndrome: a Retrospective Study of Clinical FP 4 11Profiles and Outcomes in a Tertiary CentreAnna HY Wong, YF Cheung, WC Fong, KW Fong, HF Chan, YW Ng, LT Chan, YC Chan, WT Lo, M Ismail, HM Chan, P Li
Stroke in Tuberculous Meningitis FP 5 12YP Chu, MK Fong, B Sheng, YH Chan, WT Wong, KK Lau
DISSERTATION HIGHLIGHTSTransient Axonal Glycoprotein-1 (TAG-1) Polymorphism DH 1 13and Its Correlation with Clinical Features and Prognosis in Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)Shirley YY Pang
Volume 17 # Number 6 # DECEMBER 2011
S U P P L E M E N T 5
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
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TL Kwan 關添樂
Alvin KH Kwok 郭坤豪Paul BS Lai 賴寶山Eric CH Lai 賴俊雄
Stephen TS Lam 林德深WY Lam 林永賢
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 Jacobus KF Ng 吳國夫
Hextan YS Ngan 顏婉嫦Martin W Pak 白威
PC Tam 談寶雛SW Tang 鄧兆華
William YM Tang 鄧旭明Clement CY Tham 譚智勇
Martin CS Wong 黃至生Kenneth KY Wong 黃格元
TW Wong 黃大偉Patrick CY Woo 胡釗逸
TK Yau 游子覺
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 17 No 6 # Supplement 5 # December 2011
SESSION ABSTRACT PAGEUsefulness of ABCD2 Score in Prediction of 90-day Risk DH 2 14of Stroke in Patients with Transient Ischaemic Attack in a Chinese, Non-tertiary Care Community HospitalKK Wong
Clinical Profile and Prognosis of Patients with Myasthenia DH 3 15Gravis in Hong KongEric SW Yeung
Factors Associated with the Risk of Thymoma at the DH 4 16Presentation of Myasthenia GravisKY Cheung
Predictors of Early Neurological Deterioration During Acute DH 5 17Phase of Ischaemic Stroke: Experience in Acute Stroke Unit at a Regional Hospital in Hong KongGrace LY Cheung
SYMPOSIUM ON PERIPHERAL NEUROPATHYFocal Neuropathies S 1 17Windsor Mak
Guillain-Barré Syndrome: the Immunopathogenesis and S 2 18Relationship between the Different SubtypesNobuhiro Yuki
Common Pitfalls in the Electrodiagnosis of Entrapment S 3 18NeuropathyAlex CP Chow
SYMPOSIUM ON NEURO-OPHTHALMOLOGYIdiopathic Intracranial Hypertension S 4 19BL Man
Atypical Optic Neuritis S 5 19Carmen KM Chan, Andy CO Cheng
Using Eye Movements for Topological Diagnosis of Central S 6 20DisordersDavid S Zee
NOVARTIS SYMPOSIUM ON MOVEMENT DISORDERS JOINT SYMPOSIUM WITH THE HONG KONG MOVEMENT DISORDER SOCIETYNew Targets for Treatments of Parkinson’s Disease S 7 21Ken KL Yung, John MT Chu, Cathy NP Lui, Olivia TW Ng
Levodopa/carbidopa/entacapone as First-line Levodopa S 8 21Formulation: Pharmacokinetic ConsiderationsThomas Müller
Homocysteine and Entacapone Treatment S 10 22Thomas Müller
Deep Brain Stimulation for the Treatment of Parkinson’s S 11 22DiseaseEugene C Lai
INTERNATIONAL EDITORIAL ADVISORY BOARD
Sabaratnam Arulkumaran United Kingdom
Robert AtkinsAustralia
Peter CameronAustralia
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
David WeatherallUnited Kingdom
Homer YangCanada
EXECUTIVE EDITOR
Cyrus R Kumana
MANAGING EDITOR
Yvonne Kwok 郭佩賢
ASSISTANT MANAGING EDITORS
Warren Chan 陳俊華
Betty Lau 劉薇薇
Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011 3
SESSION ABSTRACT PAGE
ORIENT EUROPHARMA SYMPOSIUM ON EPILEPSY JOINT SYMPOSIUM WITH HONG KONG EPILEPSY SOCIETYPsychogenic Non-epileptic Seizures S 12 23David G Vossler
Upcoming Antiepileptic Drugs: the United States Experience S 13 23David G Vossler
GLAXOSMITHKLINE SYMPOSIUM ON EPILEPSY JOINT SYMPOSIUM WITH HONG KONG EPILEPSY SOCIETYSleep and Epilepsy S 14 24Carl Bazil
Psychiatric Issues in Epileptic Disorders S 15 25Joyce Lam
SYMPOSIUM ON NEUROGENETICSBasic Neurogenetics: What Clinical Neurologists Need to Know S 16 25KY Mok
Molecular Neurogenetics: Tools and Methodsh S 17 26Liz YP Yuen
Advanced Neurogenetics: Frontiers in Research S 18 26KY Mok
ALLERGAN SYMPOSIUM ON HEADACHE & PAINCurrent Approach for Chronic Migraine Management S 19 27SJ Wang
Updated Guidelines for Treatment of Neuropathic Pain S 20 28PP Chen
Trigeminal Autonomic Cephalalgias S 21 29TH Tsoi
BAYER LUNCH SYMPOSIUMAnticoagulation for Prevention of Stroke in Patients with S 22 30Atrial FibrillationJaseong Koo
SYMPOSIUM ON MOYAMOYA DISEASE JOINT SYMPOSIUM WITH THE HONG KONG STROKE SOCIETY Surgical Outcomes from Revascularisation Surgery for S 23 31Moyamoya Disease: Experience in Tuen Mun Hospital, Hong KongKF Fok, WL Poon, YC Wong, Florence Kwok, Dawson Fong
Surgical Management of Moyamoya Disease S 24 32KC Wang
SYMPOSIUM ON ISCHAEMIC STROKE JOINT SYMPOSIUM WITH THE HONG KONG STROKE SOCIETY Mechanical Thrombectomy in Ischaemic Stroke: a Look at S 25 33the ToolboxFerdinand Hui
Medical Management of Intracranial Stenosis S 26 34Kazunori Toyoda
4 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
SESSION ABSTRACT PAGE
POSTERS Off-label Use of Rituximab in Refractory Neurological P 1 35Autoimmune Diseases—Experiences of a Regional Teaching Hospital in Hong KongVincent HL Ip, Alexander YL Lau, Anne YY Chan, Lisa WC Au, Florence SY Fan, Nick NC Ng, Edward HC Wong, Yannie OY Soo, Vincent CT Mok, Thomas WH Leung, Lawrence KS Wong
Cisplatin Neuropathy: a Prospective Study on Chinese Patients P 2 35KF Ko, WY Lau, WK Cheng, MC Kwan, LK Yip, KP Yiu
A Lady with Autoimmune Lymphocytic Hypophysitis P 3 36Presenting with Right 3rd, 4th and 6th PalsiesSH Li
Long-term Outcome of Stroke Thrombolysis in Hong Kong P 4 37Chinese PatientsEdward Wong
Do Cerebral Microbleeds Increase Intracranial Haemorrhage P 5 37Risk in Hong Kong Stroke Patients Receiving Thrombolytic Therapy?Edward Wong, Alexander Lau, Yannie Soo, Deyond Siu, Jill Abrigo, Tom Cheung, Venus Hui, Lawrence Wong
Intravenous Thrombolysis Versus Intra-arterial Recanalisation P 6 38Therapy for Acute Ischaemic Stroke Due to Large Artery Occlusion—Comparison of Outcomes from a Hong Kong HospitalEdward Wong, Simon Yu, Alexander Lau, Joyce Hui, Deyond Siu, Colin Graham, Cecilia Leung, Venus Hui, Lawrence Wong, Thomas Leung
The Efficacy of Deep Brain Stimulation for Advanced P 7 38Parkinson’s DiseaseYF Cheung, HF Chan, TL Poon, PMP Choi, WS Chan, FC Cheung, HM Chan, P Li
A Case with Atypical Neuroleptic Malignant Syndrome P 8 39OC Lau, BH Fung, PW Ng, CH Lo, CK Chan, KY Cheung
Headache Associated with Chest Pain and ECG P 9 39Abnormalities: What Can It Be?Raymond CK Chan, CH Lo, PW Ng
AUTHOR INDEX 40
Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011 5
Council of The Hong Kong Neurological Society
President DrLeonardSheung-waiLi李常威醫生
Vice-President DrJonasHon-mingYeung楊漢明醫生
HonSecretary DrKwok-kwongLau劉國光醫生
HonTreasurer DrWing-chiFong方榮志醫生
CouncilMembers DrEricLok-yiuChan陳樂耀醫生
DrNelsonYuk-faiCheung張煜暉醫生
DrGardianChung-yanFong方頌恩醫生
DrSonnyFong-kwongHon韓方光醫生
DrKwok-faiHui許國輝醫生
DrThomasWai-hongLeung梁慧康醫生
DrColinHiu-tungLui呂曉東醫生
ProfVincentChung-tongMok莫仲棠教授
DrBunSheng盛斌醫生
DrKin-lunTsang曾建倫醫生
DrWinnieWing-yinWong黃詠妍醫生
AdHocMember DrTak-hongTsoi蔡德康醫生
PastPresident DrPing-wingNg吳炳榮醫生
HonLegalAdvisor MrTsang-hoiKoo顧增海律師
HonAuditor MrEricLi李家祥先生
Organising Committee of the 2nd Hong Kong Neurological Congress cum 24th Annual
Scientific Meeting of The Hong Kong Neurological Society
Chairmen DrJonasHon-mingYeung楊漢明醫生
DrLeonardSheung-waiLi李常威醫生(Co-Chair)
ScientificCommittee DrWing-chiFong方榮志醫生
DrGardianChung-yanFong方頌恩醫生
DrSonnyFong-kwongHon韓方光醫生
DrKwok-faiHui許國輝醫生
DrThomasWai-hongLeung梁慧康醫生
DrColinHiu-tungLui呂曉東醫生
ProfVincentChung-tongMok莫仲棠教授
PublicationCommittee DrWinnieWing-yinWong黃詠妍醫生
DrEricLok-yiuChan陳樂耀醫生
Website DrNelsonYuk-faiCheung張煜暉醫生
DrKwok-kwongLau劉國光醫生
DrBunSheng盛斌醫生
DrKin-lunTsang曾建倫醫生
6 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
List of Speakers
Name AffiliationProfCarlBazil CollegeofPhysiciansandSurgeonsatColumbia
University,UnitedStatesDrCarmenKar-munChan HongKongEyeHospital,HongKongSARDrPhoon-pingChen AliceHoMiuLingNethersoleHospital/NorthDistrict
Hospital,HongKongSARDrAndyChi-onCheng HongKongEyeHospital,HongKongSARDrAlexChi-pingChow HongKongSanatorium&Hospital,HongKongSARDrKam-fukFok TuenMunHospital,HongKongSARDrFerdinandHui ClevelandClinicFoundation,UnitedStatesProfJaseongKoo CatholicUniversityofKorea,KoreaProfEugeneCLai TheMethodistNeurologicalInstitute,Houston,Texas,
UnitedStatesDrJoyceLam TheChineseUniversityofHongKong,HongKongSARDrWindsorMak QueenMaryHospital,HongKongSARDrBik-lingMan TuenMunHospital,HongKongSARDrKin-yingMok UCLInstituteofNeurology,UnitedKingdomProfThomasMüller StJosephHospitalBerlin-Weissensee,GermanyDrKazunoriToyoda NationalCerebralandCardiovascularCenter,Osaka,
JapanDrTak-hongTsoi PamelaYoudeNethersoleEasternHospital,HongKong
SARProfDavidGVossler UniversityofWashington,Seattle,UnitedStatesProfKyu-changWang SeoulNationalUniversityHospital,KoreaProfShuu-jiunWang NationalYang-MingUniversitySchoolofMedicine,
TaiwanProfRuey-meeiRobinWu NationalTaiwanUniversity,TaiwanDrLizYuet-pingYuen TheChineseUniversityofHongKong,HongKongSARProfNobuhiroYuki NationalUniversityofSingapore,SingaporeProfKenKLYung HongKongBaptistUniversity,HongKongSARDrDavidSZee JohnsHopkinsSchoolofMedicine,UnitedStates
Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011 7
SCIENTIFIC PROGRAMME
Venue: Grand Ballroom, leVel ll1, Kowloon ShanGri-la hotel
28 octoBer 2011, Friday
09:00 – 09:30 Registration FunctionRoom
09:30 – 11:00 FREE PAPER PRESENTATIONChairpersons: Thomas Leung, Winnie Wong
POSTER PRESENTATION
11:00 – 11:20 CoffeeBreak11:20 – 12:30 DISSERTATION HIGHLIGHTS
Chairpersons: Thomas Leung, Winnie Wong
12:30 – 13:30 Lunch13:30 – 15:00 SYMPOSIUM ON PERIPHERAL NEUROPATHY
Chairpersons: Bun Sheng, Leonard Li
Focal NeuropathiesWindsor Mak
Guillain-Barré Syndrome: the Immunopathogenesis and Relationship between the Different Subtypes
Nobuhiro Yuki
Common Pitfalls in the Electrodiagnosis of Entrapment Neuropathy
Alex CP Chow15:00 – 15:20 CoffeeBreak15:20 – 16:45 SYMPOSIUM ON NEURO-OPHTHALMOLOGY
Chairpersons: SH Ng, Nelson YF Cheung
Idiopathic Intracranial HypertensionBL Man
Atypical Optic NeuritisCarmen KM Chan, Andy CO Cheng
Using Eye Movements for Topological Diagnosis of Central Disorders
David S Zee
8 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
09:00 – 09:30 Registration FunctionRoom
09:30 – 09:40 OPENING CEREMONYWelcome Remarks: Dr Leonard SW Li
President of the Hong Kong Neurological SocietyGuest of Honour: Mr Richard MF Yuen, JP
Permanent Secretary for Food and Health (Health)
POSTER PRESENTATION
09:40 – 10:45 NOVARTIS SYMPOSIUM ON MOVEMENT DISORDERSJOINT SYMPOSIUM WITH THE HONG KONG
MOVEMENT DISORDER SOCIETYChairpersons: Mandy Au Yeung, KL Tsang
New Targets for Treatments of Parkinson’s DiseaseKen KL Yung
Levodopa/carbidopa/entacapone as First-line Levodopa Formulation: Pharmacokinetic Considerations
Thomas Müller10:45 – 11:00 CoffeeBreak11:00 – 12:35 NOVARTIS SYMPOSIUM ON MOVEMENT DISORDERS
JOINT SYMPOSIUM WITH THE HONG KONG MOVEMENT DISORDER SOCIETY
Chairpersons: Vincent Mok, XL Zhu
Routine Genetic Screening for Young Onset / Familial Parkinson’s Disease in Chinese—Are We Ready?
Ruey-Meei Robin Wu
Homocysteine and Entacapone TreatmentThomas Müller
Deep Brain Stimulation for the Treatment of Parkinson’s Disease
Eugene C Lai12:35 – 13:30 Lunch13:30 – 15:00 ORIENT EUROPHARMA SYMPOSIUM ON EPILEPSY
JOINT SYMPOSIUM WITH HONG KONG EPILEPSY SOCIETY
Chairpersons: Colin Lui, Ada Yung
Psychogenic Non-epileptic SeizuresDavid G Vossler
Upcoming Antiepileptic Drugs: the United States Experience
David G Vossler15:00 – 15:20 CoffeeBreak15:20 – 17:00 GLAXOSMITHKLINE SYMPOSIUM ON EPILEPSY
JOINT SYMPOSIUM WITH HONG KONG EPILEPSY SOCIETY
Chairpersons: Eric Chan, Howan Leung
Sleep and EpilepsyCarl Bazil
Psychiatric Issues in Epileptic Disorders Joyce Lam
29 octoBer 2011, Saturday
Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011 9
09:00 – 09:30 Registration FunctionRoom
09:30 – 11:05 SYMPOSIUM ON NEUROGENETICSChairpersons: Jonas Yeung, YL Yu
Basic Neurogenetics: What Clinical Neurologists Need to Know
KY Mok
Molecular Neurogenetics: Tools and MethodsLiz YP Yuen
Advanced Neurogenetics: Frontiers in ResearchKY Mok
POSTER PRESENTATION
11:05 – 11:20 CoffeeBreak11:20 – 12:35 ALLERGAN SYMPOSIUM ON HEADACHE & PAIN
Chairpersons: YW Chan, Edmund Woo
Current Approach for Chronic Migraine ManagementSJ Wang
Updated Guidelines for Treatment of Neuropathic PainPP Chen
Trigeminal Autonomic Cephalalgias TH Tsoi
12:35 – 14:00 BAYER LUNCH SYMPOSIUMChairpersons: Patrick Li, PW Ng
Anticoagulation for Prevention of Stroke in Patients with Atrial Fibrillation
Jaseong Koo14:00 – 15:05 SYMPOSIUM ON MOYAMOYA DISEASE
JOINT SYMPOSIUM WITH THE HONG KONG STROKE SOCIETY
Chairpersons: Dawson Fong, WC Fong
Surgical Outcomes from Revascularisation Surgery for Moyamoya Disease: Experience in Tuen Mun Hospital, Hong Kong
KF Fok
Surgical Management of Moyamoya Diseases KC Wang
15:05 – 15:20 CoffeeBreak15:20 – 17:00 SYMPOSIUM ON ISCHAEMIC STROKE
JOINT SYMPOSIUM WITH THE HONG KONG STROKE SOCIETY
Chairpersons: Raymand Lee, Sonny Hon
Mechanical Thrombectomy in Ischemic Stroke: a Look at the Toolbox
Ferdinand Hui
Medical Management of Intracranial Stenosis Kazunori Toyoda
17:00 ClosingRemarksandPresentationofAwardstoBestFreePaper,BestPosterandBestDissertationPresentations
30 octoBer 2011, Sunday
10 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
FP 13D Rotational Angiography as a Screening Imaging Test for Intracranial Stenting
Florence SY FanDepartment of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR
Background:3Drotationalangiography(3DRA)isanewtechniqueindelineatingfinedetailsofintracranialvasculature.Weinvestigatedtheroleof3DRAinselectingpatients for intracranialself-expandablestenting.Methods:Patientswhohadstrokesreferrabletoahigh-gradesymptomaticstenosiswererecruitedandunderwentscreeningforintracranialstentingbyaconventionaldigitalsubtractionangiography(DSA)anda3DRA.Bothimagingtestswereperformedbyabiplaneangiographicequipment(AlluraXperFD20/20,PhilipsMedicalSystems,Netherland).DSAconsistedofanteroposterior, lateralandbilateralobliqueviewsofthetargetarterywith10mLofiopamiro300ineachinjectionfroma4FH1catheterpositionedatinternalcarotidarteryorvertebralarteryostium.Bythesamecatheterandcontrast,3DRAwasobtainedbyarotatingarmcentredatthetargetlesion,comprising120imagesgatheredoverascantimeof4seconds.Aradiologistblindtothepatient’sclinicalinformationcomparedtheanatomyofthelesionanditsimmediatevicinityasrevealedbythetwoimagingmethods.ThedegreeofstenosiswasmeasuredbyWASIDtechnique.Lesioncharacteristicswhichmightalterthedecisionofendovasculartreatmentwererecorded.Results:PairedDSAand3DRAwereobtainedin169patients.Thetwomethodswerecomparable inthemeasurementofthestenosisseverity.However,amongthefourpatientswhohadfenestrationsmimickingoradjacenttothestenosis(middlecerebralartery=3;basilararterty=1), threewereonlyevidentin3DRAbutnotinconventionDSA.Inanotherthreepatients,angioplasty/stentingwasprecludedbasedon3DRAwhichshowedanadjacentperforatororbranchwithahighlystenosedostium.Conclusions:3DRAmaycompare favourablywithconventionalDSA indepictingminutedetailsofintracranialvascularanatomy,and ispotentiallyuseful inpreoperativeevaluationof intracranialangioplasty.
FP 2Intravenous Alteplase for Ischaemic Stroke Patients with Borderline Eligibility in Hong Kong—How Selective Should We Be?
Alexander Lau1, Edward Wong1, Yannie Soo1, Deyond Siu2, Venus Hui1, Edward Shum1, Cecilia Leung1, Colin Graham3, Thomas Leung1, Lawrence Wong1
1 Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR2 Department of Imaging and Interventional Radiology, Prince of Wales Hospital, Hong Kong SAR3 Department of Accident and Emergency Medicine, Prince of Wales Hospital, Hong Kong SAR
Background:Varianceexistsinselectingpatientsforstrokethrombolysis.UnlikeUSlabelling,intravenousalteplase(IVTPA)isnotrecommendedforage>80yearsandNIHSS>25byEuropeanguideline.Besides,bothexcludepatients>80yearsorwithahistoryofdiabetesandstrokeforthe3-4.5hourswindow.WecomparedtheoutcomesofpatientswhoreceivedIVTPAoutsidetheseguidelinestothosewhocomplied,andtoacontrolgroup.Methods:ConsecutivepatientsreceivedIVTPA<4.5hoursbetweenJanuary2007andJune2011atourcentrewerereviewed.Patientscomplianttobothguidelineswerecomparedtothosewhodidnot.TheywerefurthercomparedtoacontrolgroupwiththesameborderlineeligibilitybutwerenotgivenIVTPAduetonon-officehoursadmissionbetweenOctober2008andMay2011.Outcomemeasureswere3-monthmodifiedRankinScale(mRS)≤2andmortality,andsymptomaticintracranialhaemorrhage(SICH)accordingtoECASS(EuropeanCooperativeAcuteStrokeStudy).Results:Fifty-fourpatientsreceivedIVTPA.Thirty-threewerecomplianttobothguidelinesand21werenon-compliant.Fornon-compliantgroup(meanage81.6±8.2,NIHSS18.6±8.2),16were>80years,5hadNIHSS>25,and2thrombolysedbetween3-4.5hourshadahistoryofbothdiabetesandstrokeor>80years.Forcomparison,22non-thrombolysedcontrols(meanage77.0±10.9,NIHSS19.1±10.1)wereidentified.Twenty(61%)ofthecompliantgroupversus4(19%)ofthenon-compliantandnoneofcontrolgroupsattained3-monthmRS≤2(non-compliantvscontrol,P=0.05).Three-monthmortalityrateswere3%,43%and27%forcompliant,non-compliant,andcontrolgroupsrespectively(non-compliantvscontrol,P=0.35).SICHoccurredinone,two,andonepatientsofcompliant,non-compliantandcontrolgroups,respectively.Conclusions:TheoutcomesofpatientsgivenIVTPAoutsidebothUSandEuropeanguidelineshadpooreroutcomescomparedtothosewhofulfilled.Still,thosewhowerenotgivenIVTPAfaredevenpoorer.FurtherprospectiverandomisedtrialsareneededtosubstantiatetheuseofIVTPAinborderlineeligiblepatients.
Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011 11
Subthalamic Deep Brain Stimulation for Advanced Parkinson’s Disease: Efficacy and Complications
Movement Disorder Group, Prince of Wales Hospital, The Chinese University of Hong Kong; Anne Chan1, Jonas HM Yeung1, Danny TM Chan2, XL Zhu2, Edith Wong2, KY Lau2, Rosanna Wong3, Christine Lau1, Vincent CT Mok1, Wayne WS Poon2
1 Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR2 Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR3 Department of Occupational Therapy, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR
Background:Deepbrainstimulation(DBS)ofsubthalamicnucleus(STN)wasfirstperformedinHongKongsince1998atourcentreforpatientswithadvancedParkinson’sdisease(PD).WeherebyreporttheefficacyandcomplicationsofSTNDBSforadvancedPD.Methods:AllPDpatientswhoreceivedSTNDBSfromSeptember1998toJanuary2010wereincludedinthepresentanalyses.WecomparedtheUnifiedParkinson’sDiseaseRatingScale(UPDRS)beforeandatleast2monthsaftertheoperation.Peri-operativecomplicationswerenoted.Results:Atotalof41PDpatients(meanage,54years;21males)receivedbilateralSTNDBS.Themedianfollow-updurationwas12months(range,2-77months).Therewasasignificantoverallimprovement(31%;P<0.0001)inUPDRSinpartIII(motorperformance)postoperativelyat“onstimulationandoffmedicationcondition”comparedwithpreoperativelyat“offmedicationcondition”.Therewasalsoasignificantimprovement(32%,P<0.0001) inUPDRSpartII (functional level)score.Peri-operativecomplicationsincludedleadfracture(n=1),andleadmigration(n=1).Therewasnoperioperativemortality.Conclusions:Ourefficacyandsafetyresultswerecomparabletooverseascentres.Overall,STNDBSisaneffectiveandsafetreatmentforadvancedPD.
FP 3
FP 4Guillain-Barré Syndrome: a Retrospective Study of Clinical Profiles and Outcomes in a Tertiary Centre
Anna HY Wong, YF Cheung, WC Fong, KW Fong, HF Chan, YW Ng, LT Chan, YC Chan, WT Lo, M Ismail, HM Chan, P LiDepartment of Medicine, Queen Elizabeth Hospital, Hong Kong SAR
Background:Guillain-BarréSyndrome(GBS)isanacuteperipheralneuropathywhichispotentiallyfatalanddebilitating.Effectivetreatmentisavailable.Localdataarescarce.Inthisstudy,wereviewedtheclinicalprofilesandoutcomesofGBSmanagedinatertiarycentreinHongKong.Methods:AretrospectivestudywasperformedonGBSpatientswhomettheAsburyandCornblath(1990)diagnosticcriteriaandwereadmittedbetweenJuly2001andDecember2010totheDepartmentofMedicine,QueenElizabethHospital.DatawereanalysedbyPASWStatistics18software.Results:Wefound65GBSpatientswithinthestudyperiod;44(68%)weremale.Themeanageofonsetwas61(standarddeviation,15.7)years;94%wereChinese.Thenumberofpatientsdiagnosedperyearrangedfrom3to13.Symptomssuggestiveofantecedentupperrespiratorytractinfections(48%)andthegastrointestrinaltractinfections(11%)wererecordedrespectively.Twelvepercentofpatientshadahistoryofrecentvaccinationinthepast1to3weeks.Presentingfeaturesincludedlimbweakness(94%),facialweakness(10%),numbness(63%),visualsymptoms(14%),bulbarsymptoms(24%),hyporeflexia/areflexia(78%),ataxia(22%)anddysautonomia(27%).SimilartoCaucasianseries,acuteinflammatorydemyelinatingpolyradiculoneuropathy(AIDP)wasthecommonestsubtype(57%),followedbyaxonalsubtypes(AMANorAMSAN,21%),Fisher’ssyndrome(12%)andBickerstaffbrainstemencephalitis(2%).Aroundone-thirdreceivedintensivecareunit(ICU)careandone-fourthhadrespiratoryfailurerequiringmechanicalventilation.Seventeenpercentofpatientshadtemporarytracheostomyperformed.Fortheseselectedpopulations,themeanlengthofICUstaywas14days(95%confidenceinterval[CI],8.5-19.6)andthemeanlengthofmechanicalventilationwas25.5days(95%CI,14.4-36.7).At6months,84%ofpatientssurvivedand66%remainedindependentinactivitiesofdailyliving(ADL),asmeasuredbytheGlasgowOutcomeScale.Usingamultivariate logisticregressionmodelwithage,sex,antecedent infection/vaccination,bulbarpresentationanddiseasesubtypeascovariates,agewastheonlyprognosticfactorthatsignificantlydeterminedthe6-monthindependencyinADLbutnotsurvival.Conclusions:Inourcohort,GBScarriedsignificantmorbidityandmortality.Theonlysignificantpredictorwasage inourmodel.Larger,multicentrestudiesarewarranted forbetterdelineationofclinicalpredictorsofadverseoutcomes.
12 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
Stroke in Tuberculous Meningitis
YP Chu, MK Fong, B Sheng, YH Chan, WT Wong, KK LauDepartment of Medicine, Princess Margaret Hospital, Hong Kong SAR
Background:Theobjectiveof this studywas to identify thepredictorsof stroke inpatientswithtuberculousmeningitis(TBM)andtheirprognosticimplications.Methods:AllpatientswithTBMinPrincessMargaretHospitalfrom2000to2010wereincludedinthestudy.Ofthe34patientswithTBM,16patientsdevelopedstroke.Potentialpredictorsofstrokeincludingco-morbiditiesandbiochemicalfindingswerestudied.Radiologicalexaminationsincludingcomputedtomographyormagnetic resonance imagingbrainwerealsostudied.TheneurologicaloutcomemeasuredwasmortalityrateandModifiedRankinScoreat6months(0-3vs4-6).Results:Patientswithstrokewereolder(55.4±15.2vs45.9±16.6;P=0.09)andhadlowercerebrospinalfluid(CSF)–to–serumglucoseratio(0.24±0.14vs0.33±0.14;P=0.09).TherewerelessHIVpatientsinthosewithstroke(6.3%vs22.2%;P=0.19).MostoftheinfarctsinTBMweremultiple(87.5%),bilateral(62.5%),andlocatedinbasalganglion(31.3%)andsubcorticalwhitematter(50%).Patientswithstrokehadahighermortalityrate(31.2%vs11.15%;oddsratio[OR]=3.64;P=0.147)andmoreadverseneurologicaloutcomeat6months(56.2%vs29.4%;OR=3.09;P=0.119).HighCSFtotalprotein(2.59±1.3vs1.57±0.53;P=0.0096)andolderage(64±13.2vs44.4±14.5;P=0.014)wereassociatedwithadverseneurologicaloutcomeat6monthsinTBMpatientswithstroke.Conclusion:StrokeiscommoninpatientswithTBMleadingtoahighermortalityandworseneurologicaloutcome.
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Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011 13
DH 1Transient Axonal Glycoprotein-1 (TAG-1) Polymorphism and Its Correlation with Clinical Features and Prognosis in Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Shirley YY PangDepartment of Medicine, Queen Mary Hospital, Hong Kong SAR
Background:Chronicinflammatorydemyelinatingpolyradiculopathy(CIDP)isaheterogeneousgroupofacquireddisorderscharacterisedbyperipheralnervedemyelination.Previousstudieshaveshownagoodresponse to immunotherapybutasignificantproportionofpatientscontinue to requiremaintenance therapy.A recentstudy identifiedapotentialgeneticmarker for responsiveness tointravenousimmunoglobulin(IVIG).Inthisstudy,CIDPpatientswereexaminedtolookforassociationbetweenclinical,electrophysiologic,geneticfactorsandtreatmentresponseaswellasriskoftreatmentdependence.Methods:Case recordsof32CIDPChinesepatientsdiagnosedbetween January1995andMarch2010at the threeNeurologycentresonHongKongIsland(namely,QueenMaryHospital,PamelaYoudeNethersoleEasternHospital,andRuttonjeeHospital)werereviewedtoexaminetheirclinicalfeatures,electrophysiologicparametersonpresentation,diseasecourseandoutcome.Bloodsampleswereavailablefrom22patientsand147controls.DNAwasextractedfromperipheral leucocytesandthetransientaxonalglycoprotein1 (TAG-1)genotypefor thepreviouslyreportedsinglenucleotidepolymorphism(SNP)wasdeterminedusingtheSequenomMassARRAYsystem.Results:Theoverallresponseratetoimmunotherapywithprednisolone,IVIGorplasmaexchange(PE)was80%withnodifferencedetectedamongthethreetherapies.Clinicalfeaturessuchasageofonset,durationofsymptoms,presenceofdiabetesmellitus(DM),presenceofsensorysymptomsandmodifiedRankinscore (mRS)onpresentationdidnotpredict treatmentresponsiveness.Electrophysiologicparametersontheinitialnerveconductionstudywerealsonotassociatedwithtreatmentresponse.Fifty-eightpercentofourpatientsweredependentonmaintenancetherapyafterameanfollow-upperiodof5.8years.Clinicalfeaturessuchasageofonset,durationofsymptomsandpresenceofDMwerenotpredictiveoftreatmentdependence.Patientswithmoreprolongeddistalmotorlatency(DML)intheupperlimbshadahigherriskoftreatmentdependence(P=0.03,OR=1.03).Patientswithahighermeanmotornerveconductionvelocity(NCV)intheupperlimbsshowedatrendoflowerriskoftreatmentdependencebutthisdidnotreachstatisticalsignificance.TAG-1genotypesin147healthycontrolsandin22CIDPpatientswithregardtotheSNPdesignatedbyrs2275697weredeterminedandnosignificantdifferenceinallelefrequencywasdetected.Furthermore,amongCIDPpatients,therewasnoassociationbetweenTAG-1genotypeandageofonset,presenceofDM,modeofonsetanddiseasecourse.However,thosewhowerehomozygousforGhadsignificantlymoreprolongedDML.ThosewiththeGallelepresent(patientswhowereeitherhomozygousforGorheterozygouswithG/A)hadsignificantlylowercompoundmuscleactionpotential(CMAP)amplitudeintheupperlimbsandmoreprolongedDMLinthelowerlimbsthanthosehomozygousforA.Conclusions:TheoveralltreatmentresponserateinCIDPishighandevenpatientswithadvancedage,unfavourableelectrophysiologicfeaturesandseveredisabilitycanimprovewithtreatment.However,asignificantproportionwillrequirelong-termmaintenancetherapytopreventrelapses.PatientswhoseinitialnerveconductionstudyshowedmoreprolongedDMLintheupper limbswereat increasedriskofbeingtreatmentdependent.TheTAG-1GallelewasfoundtobeassociatedwiththeseverityofdemyelinationontheinitialnerveconductionstudyinCIDPpatients,whichsuggestsaroleofTAG-1inthepathogenesisofdemyelination.
14 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
Usefulness of ABCD2 Score in Prediction of 90-day Risk of Stroke in Patients with Transient Ischaemic Attack in a Chinese, Non-tertiary Care Community Hospital
KK WongDepartment of Medicine and Geriatrics, Yan Chai Hospital, Hong Kong SAR
Background:Strokewasthesecondcauseofmortalityworldwidein2004andrankedthefourthcauseofdeath inHongKongin2008. Itwasfrequentlyprecededbytransient ischaemicattack(TIA).TIAisrecognisedtobeamedicalemergencybecause itsrisksofearlystrokearehigh.VariousclinicalpredictiontoolsareproposedtoaidtheriskstratificationafterTIA.The“ABCD2”scoresareattemptedtoquantifythisrisk.Thosewiththehighestscoreshavesignificantlyincreasedriskofearlystroke.Thesescoreshadbeenvalidatedinseveralstudiesbutwerenotuniversallysuccessfulindifferentpopulations.Aim:ThepurposeofthestudywastoevaluatetheABCD2scoreinpatientswithTIAandtheriskofsubsequentstrokeinalocalChinese,non-tertiarycommunityhospital.Methods:From1January2004to31December2009,allpatients’recordswithprincipaldiagnosisas‘transient ischaemicattack’(TIA)codedbyICD9hadbeenretrieved.IncidenceofstrokeamongTIApatientshadbeenidentifiedat90days.Allthebaselineparameterswererecorded.IncidenceofstrokeamongTIApatientshadbeenidentifiedat90days.ABCD2scoreswerecalculatedretrospectively.Fromthedifferentialstrokeincidence,thepatientswithTIAhavebeendividedintotwogroupswithdifferentABCD2scoresforfurtherstatisticalcomputation.Primaryoutcomewasstrokewithin90daysafterTIA.SecondaryoutcomesarecardiovasculardiseasesincludingrecurrentTIAoracutestroke,cardiovasculardiseaseanddeath.Results:Therewereatotalof446patientswithdiagnosisofTIArecruited.Ofthem,23(5.4%)hadbeenrejected.Thetotal90-dayincidenceofstrokeinrecruitedpatientswas5.2%(22patients).Morethanhalfofthestrokerecurrenceoccurredwithin7days(4patients,18%)and30days(9patients,41%)whereastheremaining(9patients,41%)wereat90days.PatientswerecategorisedintotwogroupswithABCD2scoreat5.Therewassignificantdifferencein90-daystrokeincidencebetweenhigh(16patients,72.7%)andlow(6patients,27.3%)ABCD2score(P=0.047).Oddsratiowas2.817.TheKaplan-Meiersurvivalcurvefor90-daystrokeofdichotomisedABCD2scoreat5wasplotted.Pvalueoflog-ranktestwas0.0295.Conclusion:OurstudyhasconfirmedtheusefulnessofABCD2scoreinpredictingthe90-daystrokeriskinpatientswithTIAinaChinese,non-tertiarylocalcommunityhospital.ThosewithhighABCD2scorewouldbeassociatedwithhigher90-daystrokeincidence.MoreresourcesshouldbeallocatedtothosewithhigherABCD2scoreinTIApatients.
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Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011 15
DH 3Clinical Profile and Prognosis of Patients with Myasthenia Gravis in Hong Kong
Eric SW YeungDepartment of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR
Background:Myastheniagravis(MG)isthecommonestneuromuscularjunctiondisorder.Previouslocalstudiesreportedanannualincidenceof4permillion,whilelatestwesternfiguresaremuchhigher.Withadvancesintreatment,theprognosisofMGpatientshasmuchimprovedinwesterncountriesoverthepastdecades.Howeverthereisascarcityoflocaldata.Objectives:Ourstudyhas fourobjectives: (1) tostudydemographicsandclinicalcharacteristics inpatientswithMG;(2)toexaminetheutilisationofvariousdiagnosticmodalitiesforMG;(3)toreviewourexperienceinmanagementofthedisease;and(4)todeterminetheclinicaloutcomesandprognosisofMGinChinesepatients.Method:This isaretrospectivereviewofpatientswithMGattendingourNeurologyunitofPamelaYoudeNethersoleEasternHospitalbetween1October1993and31December2010.Patientswereidentifiedbytheclinicaldatasystem(CDARS)withthediagnosisofMG,anddividedintothreegroups(ocular,generalised,oculartogeneralised)forcomparison.Demographics,clinicalprofile,historyofhospitalisationandintensivecareunitcare,myasthenic/cholinergiccrisis,investigationresults,treatmentmodalities,outcomeatthetimeofanalysisincludingfunctionalstatusandmortalitywereretrievedfromtheclinicalmanagementsystem(CMS)andhospitalchartsforreviewandanalysis.Factorsassociatedwithmortality,generalisationinocularonsetpatientswerestudied.Results:Atotalof152patientswereidentified.Twopatientswerelosttofollow-upandexcluded.Themeanageatdiagnosiswas51.18(range,13-91)years.Afemalepredominancewasnotedinallage-groups.Theannualincidencewas13.3permillion(range,8.3-23.3).OcularMGcomprisedthemajority(59.3%).Fifteenpatientshadocularonsetanddelayedgeneralisationofsymptoms,alloccurringwithin30(range,1-30)months.Significantassociatedfactorswithgeneralisationincludedpositiveanti-acetylcholinereceptor(anti-AChR)antibody,positiverepetitivestimulationtest(RST),andpresenceofpathologicallyconfirmedthymoma.Theanti-AChRantibodywasthecommonesttestperformed(92.7%)whileTensilontesthadthehighestpositiverate(75%).25.5%ofpatientshadthymomaoncomputedtomography(CT)scanofthorax.91.3%ofpatientswereonmestinon.40.7%wereonsteroids.39patientsrequiredin-patientmanagementoftheirMGexacerbation, leadingtoameanhospitalstayof7.95(range,2-125days).22patientshadmyastheniccrises,alloccurringbeforetreatmentwithstandardimmunotherapy.Thymectomywasdonein23patients,with19pathologicallyconfirmedthymomas.FourpatientsdiedofMG-relatedcomplications:threefromrespiratoryfailureandpneumonia,onefromseveresepsiswhileoncorticosteroid.Thedisease-relatedmortalitywas2.7%overameandiseasedurationof9.65(range,1-51years).Noriskfactorassociationwithmortalitywasidentified.Allsurvivingpatientsachievedclinicalremission,withmodifiedRankinScaleof0or1.Conclusion:MGwascommoninourlocality,withanannualincidencecomparabletowesternstudies.Noneoftheinvestigationmodalitieswassatisfactorytoserveasthe“goldenstandard”fordiagnosis.Utilisationofcurrentpharmacologicaloptionswasadequate,butthymectomywas lessconsidered.Prognosisisgoodinourgroup,comparabletowesterncountriesandpreviouslocalexperience.
16 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
Factors Associated with the Risk of Thymoma at the Presentation of Myasthenia Gravis
KY CheungDepartment of Medicine, Tuen Mun Hospital, Hong Kong SAR
Background:Thymoma is found in10 to15%ofpatientswithmyastheniagravis (MG).Thymoma-associatedMGisconsideredtobeamoreseverediseaseandallthymomapatientsareindicatedforthymectomy.ItisunclearwhethercertainclinicalorserologicalfindingsofMGpatientsatthetimeorearlyafterthediagnosiscanpredictthepresenceofthymoma.Objective:Todeterminethedemographic,clinicalaswellasautoimmuneantibodycharacteristicsthatmaydifferentiatebetweenthymoma-associatedMGandnon-thymoma–associatedMGintheearlycourseofthedisease.Comparisonfortheclinicalcoursesduringthewholefollow-upperiodofMGpatientswithorwithoutthymomawasalsomade.Methods:WeretrospectivelyevaluatedMGpatientsfollowedupatTuenMunHospital inHongKongfromyear2000to2010.MGwasdiagnosedbythetypicalhistoryandsignsoffluctuatingandfatigablemuscleweaknesswithitsassociationswiththefollowingvariables:thetitreofanti-acetylcholinereceptorantibody,anunequivocalclinical improvement inresponsetoanticholinesterase inhibitors,andadecrementalpatternonrepetitivenervestimulationtestandthestatusofthymomaonimagingstudy.Thebaselinecharacteristics,clinicalpresentation,coursesofdiseaseduringtheearlyandthewholefollow-upperiods,treatmentsoffered,anti-acetylcholineautoantibodytitersaswellastheotherassociatedautoimmunediseaseswererecordedandcomparedbetweenthegroupswithorwithoutthymoma.Results:Atotalof184MGpatientswhofulfilledthecriteriawereidentifiedandfollowedup.Thymomawasdiagnosedin19.6%ofthem.Themeanageofpatientswiththymomawasolder(55.08vs44.56;P=0.042);femalesexwasmoreprevalent(femalevsmaleratioof1.4vs1)butthesexratiowassimilarwhencomparedwiththosewithoutthymoma.AlthoughthepresentingsymptomsandbaselineMGFAscoresweresimilar,thymoma-associatedpatientshadasignificantlymorerapiddeteriorationofMGandmoreseverediseasewithhighermeanofmaximumMGFAscore(2.81vs1.26;P<0.001)withinthefirst6monthsoffollow-up,andwerealsomorelikelytodevelopgeneralisedMGeventually(83.3%vs38.5%;P<0.001)whencomparedwithnon-thymomagroup.Allthymomapatientshadpositiveanti-acetylcholinereceptorantibodyandahighertitrewasrecorded.Theirlong-termoutcomewascomparabletonon-thymoma–associatedMGpatientswithsimilarMGFAscoreon last follow-up.Autoimmunediseasewaspresentin37%ofpatientsoverallwiththyroiddiseasebeingthecommonestassociation.Usingmultivariatelogisticregressionmodel,ahighMGFAscoreat6months(MGFA3-5)andaveryhighanti-AChRtitre(>19nmol/L)werepredictiveofthymoma.Conclusion:MGpatientsatriskofthymomacouldbeidentifiedduringtheearlycourseofthedisease.AhighMGFAscoreat6monthsandaveryhighanti-AChRtitrepredictedtheoccurrenceofthymoma.
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Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011 17
DH 5Predictors of Early Neurological Deterioration During Acute Phase of Ischaemic Stroke: Experience in Acute Stroke Unit at a Regional Hospital in Hong Kong
Grace LY CheungDepartment of Medicine and Geriatrics, Tuen Mun Hospital, Hong Kong SAR
Background:Patientssufferingfromacuteischaemicstrokeareatriskofneurologicaldeteriorationwithinthefirstfewdaysafterstrokeonset.Thefrequency,clinicalcharacteristicsandcontributingfactorsofearlyneurologicaldeteriorationduringtheacutephaseofischaemicstrokeinalocalhospitalinHongKongwereinvestigated.Methods:ConsecutiveacuteischaemicstrokepatientsadmittedtotheAcuteStrokeUnitatTuenMunHospital,amajor regionalhospital located in theNewTerritoriesWest,HongKongwerestudiedprospectively.Demographicalcharacteristics,clinicalparameters,computedtomographic(CT)brainfindingsandlaboratoryresultswereevaluated.TheNationalInstituteofHealthStrokeScale(NIHSS)wasusedtoassessstrokeseverityandneurologicaldeficits.AssessmentsusingNIHSSwereperformedatbaselineandafteradmission.EarlyneurologicaldeteriorationwasdefinedasanincreaseinNIHSSscoreby4ormorepointsfrombaselinewithin7daysfromstrokeonset.Results:Atotalof110acuteischaemicstrokepatientswererecruited,ofwhom27(24.5%)sufferedfromearlyneurologicaldeterioration.ThepredictivefactorsofearlyneurologicaldeteriorationincludedahighbaselineNIHSSscore(P<0.001), lowGlasgowComaScalescoreonadmission(P<0.001),andbaselineCTbrainfindingsofinfarctsoncoronaradiata(P=0.024),territorialinfarcts(P<0.001),cerebraloedemaorpressureeffects(P<0.001),hyperdensemiddlecerebralarterysign(P<0.001)andhaemorrhagicinfarcts(P=0.002).Cerebralsmallvesseldisease(P<0.001)andlacunarinfarctsonCTbrain(P=0.001)wereprotectivefactors.Thosewhohadearlyneurologicaldeteriorationweremorelikelytohavediedat30days(33.3%vs1.2%;P<0.001)andhadalongerlengthofhospitalstay(24.3daysvs13.8days;P=0.025).Conclusion:Earlyneurologicaldeteriorationinacuteischaemicstrokeiscommon.Itisassociatedwithhigherriskofearlydeathandlongerlengthofhospitalstay.Thesepatientsmaybeidentifiedearlyattheirpresentations.Agreatsenseofawarenessandpromptinvestigationandmanagementareinneedtopreventitsoccurrence.
Focal Neuropathies
Windsor MakDepartment of Medicine, Queen Mary Hospital, Hong Kong SAR
Focalneuropathyisaproblemfrequentlyencounteredinclinicalpractice.Differentpatientgroupstendtohavedifferentunderlyingaetiologies.Patientswithdiabetesmellituscanhaveacutemononeuropathyaffectingthecranialaswellasperipheralnerves.Besides,theyaremorepronetochronicentrapmentneuropathies.Diabeticamyotrophyisalsoafocalproblembutpatientscanpresentheterogeneously.Vasculiticmononeuropathyandmononeuropathymultiplexcanbeseeninsomeconnectivetissuediseases.Thisconditionmayalsooccurinisolationintheabsenceofextra-neural involvement.Theelectro-andhistologicaldiagnosisofvasculiticmononeuropathymultiplexwillbediscussed.Apartfromdiabeticpatients,entrapmentneuropathyatmultiplesitescanoccur inhereditaryneuropathywithliabilitytopressurepalsiesandattheearlystageofGuillain-Barrésyndrome.Thesemodelsareillustrationsofthedouble-crushphenomenon.FocalinvolvementcanalsobeseeninmotorneuropathywithmultifocalmotorconductionblockandtheCANOMADsyndrome,whicharerarevariantsofchronicinflammatorydemyelinatingpolyneuropathy.
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18 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
Guillain-Barré Syndrome: the Immunopathogenesis and Relationship between the Different Subtypes
Nobuhiro YukiDepartments of Microbiology and Medicine, National University of Singapore, Singapore
The recentadvances inGuillain-Barré syndromeresearchhave improvedourunderstandingoftherelationshipbetweenthedifferentsubtypes.Thethreemajorsubtypesareacute inflammatorydemyelinatingpolyneuropathy(AIDP),acutemotoraxonalneuropathy(AMAN)andFishersyndrome,variationsintheclinicalpresentationsarelikelytorepresentdifferentendsofacontinuousdiseasespectrum.AIDP,whichfrequentlypresents facialpalsiesanddistalparesthesia, isassociatedwithcytomegalovirusandEpstein-Barrvirusinfections.‘Facialdiplegiaandparesthesia’showssubclinicalmotornervedemyelinationin limbsandisassociatedwithbothinfections,supportingthatthis isaregionalformofAIDP.AMANandFishersyndromeareassociatedwithCampylobacter jejunienteritis.C jejuni sialyltransferasegenepolymorphismdeterminestheganglioside-like lipo-oligosaccharidestructure.GM1-orGD1a-likelipo-oligosaccharideinducesanti-GM1or-GD1aautoantibodies,causingAMAN;whereas,GQ1b-likelipo-oligosaccharidestriggersanti-GQ1bantibodiescausingFishersyndrome.ThissuggeststhatAMANandFishersyndromearepartofthesamediseasespectrumalongwiththepresenceofoverlappingcasesofAMANandFishersyndrome.DependingontheseverityofnerveinsultinAMAN,thisautoimmuneattackcausesthelessextensive‘acutemotorconductionblockneuropathy’ormoreextensive‘acutemotor-sensoryaxonalneuropathy’subtypes.AlthoughtypicallyassociatedwithFishersyndrome,anti-GQ1bautoantibodiesarealsoassociatedwithacuteophthalmoplegiawithoutataxia, isolatedinternalophthalmoplegia,acuteoropharyngealpalsy,ataxicGuillain-Barrésyndrome,acutesensoryataxicneuropathy,Bickerstaffbrainstemencephalitisandpharyngeal-cervicalbrachialweakness,suggestingthatthesedifferentclinicalpresentationsarealsopartofacontinuousdiseasespectrum.
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S 3Common Pitfalls in the Electrodiagnosis of Entrapment Neuropathy
Alex CP ChowDivision of Rehabilitation, Hong Kong Sanatorium & Hospital, Hong Kong SAR
Carpal tunnel syndrome and ulnar nerve entrapment at the elbow are common entrapmentneuropathies.Althoughthesetwoconditionsarecommonlyseen,andtheperformanceofmotorandsensoryconductionstudiesarewelldescribedinstandardtextbooks,theelectrodiagnosticevaluationis frequentlycomplexandchallenging toeven themostexperiencedelectrodiagnosticmedicineconsultants.Anumberofthemorecommonpitfallsanditsconsequenceswouldbediscussed.
Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011 19
Idiopathic Intracranial Hypertension
BL ManDepartment of Medicine, Tuen Mun Hospital, Hong Kong SAR
Idiopathicintracranialhypertension(IIH)isdefinedasincreasedintracranialpressurewithoutaspace-occupyinglesionorhydrocephalusandnormalcerebrospinalfluidcomposition.IIHispredominantlyseeninwomenofchildbearingageandassociatedwithahistoryofrecentweightgain.Itisassociatedwithlossofvisualfunctioninupto25%ofcasesandprogressiontoblindnessifuntreated.TheincidenceofIIHisincreasingbecauseofanincreasedawarenessofthesyndromeandtheincreasingprevalenceofobesity.Thediagnosticevaluationofthesepatientsofteninvolvesseveralmedicalsubspecialties.Coordinatingthepatient’scarefrompresentationtofollow-upisanenormouschallenge.ThistalkoffersanupdatedreviewofIIH, includingepidemiologyandpathogenesis,clinicalpresentations,commonclinicalcourse,diagnosticcriteriaandchallenges,andtreatmentsandprognosis.
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S 5Atypical Optic Neuritis
Carmen KM Chan, Andy CO ChengHong Kong Eye Hospital, Hong Kong SAR
Typicallyweassociateopticneuritiswithretrobulbar,demyelinatingopticneuritis,whichoccurs inyoungfemales.Itmaybeassociatedwithmultiplesclerosis,anditusuallyimprovesspontaneouslywithnotreatment.WhilstthisscenariomaybetrueintheCaucasianpopulation,itisnotinfrequentthatweencounter‘atypical’opticneuritisintheChinesepopulation.Ifwemanage‘atypical’opticneuritisliketypicalones,wemaymisstheimportanttherapeuticwindow. Inthistalkwewillcoverthedifferentialdiagnoses,causesandmanagementofatypicalopticneuritis,andconditionswhichcanmimicopticneuritis.Therewillbeparticularemphasisonneuromyelitisopticaandopticperineuritis.
20 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
S 6Using Eye Movements for Topological Diagnosis of Central Disorders
David S ZeeProfessor of Neurology and Ophthalmology, Johns Hopkins School of Medicine, United States
Herewewillfocusonacarefulbedsideexaminationofeachoftheocularmotorsubsystems(saccades,pursuit,vestibularandvergence)tolocaliseandunderstandourpatients’eyemovementdisorders.Wewillapproachsaccadedisordersbasedonabnormalitiesininitiation,amplitudeandspeed,andlocalisethemtothecerebrum,brainstemorcerebellum.Wewillcomparemidbrain,pontine,medullaryandcerebellarlesionsandtheireffectsonsaccades.Midbrainlesionscauseverticalsaccadeslowing;pontinelesionscausehorizontalsaccadeslowingandmedullaryandcerebellarlesionscausesaccadeinaccuracy(dysmetria).Cerebellarvermal lesionscausesaccadehypometriaanddeepcerebellarfastigialnucleilesionscausesaccadehypermetria.Disordersofsaccadeinitiationreflecthigherlevel lesionsinthecerebralhemispheres.Pursuitdisordersarehardertolocalisebutcerebralhemispherelesionsproduceipsilateralsmoothpursuitdeficitsandcontralateralsaccadeinitiationandamplitudedeficits.Cerebellarlesions(primarilyflocculusandparaflocculus[tonsils])producemarkedpursuit(andeccentricgazeholding)deficits. Weapproachnystagmusandotherocularoscillationsusingaclassificationbasedfirstuponwhethertheslowphaseorthequickphaseistheprimaryabnormality.Wewillbuildadecisiontreebasedonwhichistheprimaryabnormality.
A Flow Chart For Classification Of NystagmusIsfixationimpairedbecauseofaslow drift,oranintrusive saccade,awayfromthetarget?
Ifaslow drift isculprit
Jerk
Unidirectional
Central Peripheral
Pendular
Acquired(MSorOPT)orCongenital
Changesdirectionwithdirectionofgaze(gaze-evoked)Vestibular(constant
velocity)
(Useeffectoffixationandvectorofnystagmus)
Changesdirectionwithviewingeye=LatentNystagmus
Acquired(velocitydecreasinge.g.cerebellar
Congenital(velocityincreasing)
A Flow Chart For Classification Of Nystagmus
Ifasaccadeawayfromthefixationtarget(saccadicintrusion)istheculprit?
Withanintersaccadicinterval(~200ms)beforeareturnsaccade
Square-wavejerks(smallsaccadesawayfromandbacktofixation),macrosquarewavejerks(muchlargersaccades)
Macrosaccadicoscillations,largesaccadesaroundfixation(extremedegreeofsaccadehypermetria)
Withoutanintersaccadicinterval(backtobacksaccades)
Opsoclonus(multiaxis)
Flutter(oneaxis)includes‘voluntarynystagmus’
OcularbobbingSingleverticalsaccadeawayfromfixationfollowedbyslowdriftback
Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011 21
New Targets for Treatments of Parkinson’s Disease
Ken KL Yung, John MT Chu, Cathy NP Lui, Olivia TW NgDepartment of Biology, Hong Kong Baptist University, Hong Kong SAR
ClinicalmanagementofParkinson’sdisease involvespharmaceutical interventionsanddeepbrainstimulation.Variable resultsare found indifferentpatientsand thereareneeds to look fornewtreatments.Dataobtainedfromlaboratorieshaveimplicatedthattherearepotentialtargetstoofferneuroprotectiontodopaminergicorprovidecellreplacementofdopaminergicneurons.Thepresenttalkwill focusonseveralaspects.Firstly,rolesandmechanismsofneurokininsandtheirreceptors,namelyNKreceptors,willbediscussed.RecentresultsinourlaboratoryhaveshownthatactivationofNK1receptorsisneuroprotectivewhereasactivationofNK3receptorsisdetrimentaltothesurvivalofdopaminergicneurons.Secondly,rolesofN-methyl-D-aspartatereceptor(NMDAR)2Bingenerationofcelldeathsignallinghavebeeninvestigated.GenesilencingapproachhasbeenemployedinreducingthefunctionalexpressionofNMDAR2Bproteinsinanimals,andtheseapproacheshavebeenfoundtoprovideneuroprotectiveeffectstothedopaminergicneurons.Moreover,wehavealsodiscoveredthatthereareexpressionsofreactiveastrocyteswithinanextremelyshorttimewindowaftertheonsetofParkinson’sdiseaseinanimals.Thereactiveastrocytesexpressmarkerofneuralstemcellsandtheyarefoundtoreleaseneurotrophicfactorswhichcanprotectdegenerationofdopaminergicneuronsandtheirterminals.Thereforereactiveastrocytesarepotentialcellsthatcanbeemployedincellreplacementtherapyinregenerativemedicine.Takingall together,therearepotentialnewtargetsforParkinson’sdiseaseandsomeofthosecouldbetakenintoaccountfordevelopmentofnewapproachesinclinicalmanagementofParkinson’sdisease.
AcknowledgementThe present work was supported by General Research Fund (HKBU 262107 and 262210), Hong Kong Research Grants Council and Hong Kong Baptist University RC/AoE/08-09/02.
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S 8Levodopa/carbidopa/entacapone as First-line Levodopa Formulation: Pharmacokinetic ConsiderationsThomas MüllerDepartment of Neurology, Center for Parkinson’s disease and Multiple sclerosis, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, 13088 Berlin, Germany
Levodopa(LD)isthemostefficaciousandbesttoleratedcompoundforthetreatmentofpatientswithParkinson’sdisease(PD).Thiscompoundisrapidlymetabolisedinparticularbytheenzymesaromaticdopadecarboxylase(DD)andcatechol-O-methyltransferase(COMT).InhibitionofDDwithcarbidopa(CD)markedlyreducestheperipheralLDdegradation.Buttheshortplasmahalf-lifeofLD/CDpreparationslimits itsclinicalbenefit.Therefore,followingtheLDtransport intothebrainandtheconversiontodopamine,analternatingstimulationofnigrostriatalpostsynapticdopaminereceptorstakesplace.Inthelongtermthesefluctuationsofdopamineconcentrationssupportonsetofmotorcomplications(MC)inPDpatients.GeneralopinionisthatlossofcentralcompensatorymechanismsofdopaminemetabolismisresponsibleforthedevelopmentofMC.However,intheperiphery,LDtroughsarepreponderantlyassociatedinclinicalpracticeaccordingtopharmacokineticinvestigationswiththeMCwearingoff,whichisthereappearanceofmotorsymptomswithdecreasingdrugeffect.ApossiblestrategytoprolongplasmametabolismofLD/CDistheadditionofaCOMTinhibitor,ieentacapone(EN).Accordingly,combinationoftheCOMTinhibitorENtoLD/CDimprovedwearingoff,sinceENprolongsLDhalf-lifeandavoidstroughs.PharmacokinetictrialswithPDpatientsalsoshowedthatplasmaLDpeaksaremostlyrelatedtotheclinicalmanifestationoftheMCdyskinesia,whichappearasinvoluntarymovements.OnetimeadditionofENtoaLD/CDformulationshowednoincreaseofperipheralmaximumLDconcentration.ButrepeatcombinationofENtoeachLD/CDintakeelevatedplasmaLDbioavailabilityandpeaks.ThereforeswitchfromaLD/CD–toaLD/CD/ENregimenmayalsoaskforreductionofLD/CDdosingordelayofthenextLD/CDintake,toavoidonsetofthemostcommonpeakdosedyskinesia.MoreoveritmaybeusefultostartwithhigherdosingofLDformulationsinthemorningandthentotitratewithdifferentLDdosagesduringthedayaccordingtotheindividualpatient’smotorbehaviourinmoreadvancedstagesofPD,asLDplasmaavailabilitytendstoaccumulateduringthedaywithrepeatedLDdosing.Thisapproachmayalsopreventonsetofdyskinesia.Inconclusion,pharmacokineticstudiesonperipheralLDmetabolismandmodeofintakeunderlinetheirimportanceasperipheralcomponentsforMCmanifestationsinPDpatients.ThesepharmacokineticfindingsinPDpatientsandhealthyvolunteersontheimpactofCOMT-inhibitiononLDplasmabehaviourmayalsosuggest,thatLD/CD/ENasfirst-lineLDformulationmaybemoreappropriate.LD/CD/ENprovideslessfluctuatingLDplasmalevels,asshownbypharmacokinetictrials.Fromtheclinicalpointofview,LDtherapyis lesscomplex,whenLD/CD/ENis introducedasfirst-lineLDformulation,if tolerated, inPDpatients.ThisapproachcircumventstheabovementionedCOMT-inhibitorrelatedadaptionofLDintakefollowingtheonsetofwearing-offphenomenaduringrepeatedLDintake.SuchaswitchfromLD/CDtoLD/CD/ENmaybecomplexinparticularinmoreadvancedPDpatients,asitmayaskforarepeatedchangeofLDdoses,ofnumberofintakesandofdosingintervals.
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Homocysteine and Entacapone Treatment
Thomas MüllerDepartment of Neurology, Center for Parkinson’s disease and Multiple sclerosis, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, 13088 Berlin, Germany
Thesagaofharmfuladministrationoflevodopa(LD)inthetreatmentofParkinson’sdisease(PD)resultedfromoutcomesofanimal,andcellculturestudiesandtheclinicalobservationofmotorcomplicationsrelatedtotheshortplasmahalf-lifeofthedrug.Thisdiscussiondidonlypartiallyconsiderafurtheraspect,which isassociatedwith the long-termadministrationofLD.ChronicLD intake increaseshomocysteine levels,whichmaysupportprogressionof thediseaseduetoconcomitantonsetofneuropsychiatricsymptomsandcomorbidities, i.e.vasculardisease.Homocysteinedecreasemaythereforebeafuturetherapeuticchallenge,whichmaybeachievedbysupplementationwithcertainvitaminorLD/DDIadministrationwithacatechol-O-methyltransferase(COMT)inhibitor.Monitoringofhomocysteinemayalsoserveasbiomarkerforthedetoxificationpotentialofendogenous,exogenousandenvironmentaltoxins.Thesesubstratesmayalsoaccumulateinthenervoussystem,ashomocysteinesynthesisisassociatedwithO-methylationwhichhasabroaddetoxificationpotential.Intheperiphery,therapeuticapproachesforthisLDmediatedhomocysteineincreasearevitaminsupplementation,iefolicacid,orapplicationofLDwithaninhibitorofCOMT.Inthebrain,abloodbraintrespassingprecursoroffolicacidoracentrallyactingCOMTinhibitormayrepresenthypotheticaltherapeuticapproaches.ThisCOMTinhibitorshouldbeappliedtogetherwithanoxidativestressreducingMAO-B-inhibitor,inordertoforcecentraldopaminemetabolismfurtherdownviathemethylationpath.
Deep Brain Stimulation for the Treatment of Parkinson’s Disease
Eugene C LaiThe Methodist Neurological Institute, Houston, Texas, United States
Deepbrainstimulation,whichinvolvestheimplantationofadevicethatsendselectrical impulsestospecifictargetsinthebrain, isthesurgicaltreatmentofchoicewhenParkinson’sdisease(PD)motorcomplicationsareinadequatelymanagedwithmedications.Thispresentationwilldiscussthefindingsofadouble-blinded,randomisedcontrolledtrialcomparingbestmedicaltherapy(BMT)anddeepbrainstimulation(DBS)ofthesubthalamicnucleus(STN)andglobuspallidus(GPi)forthetreatmentofPD.Atotalof255patientswithidiopathicPDwereenrolledinPhaseIofthestudy.After6months,DBSwasmoreeffectivethanBMTinimprovingontimewithouttroublingdyskinesia,motorfunction,andqualityoflife,butwasassociatedwithanincreasedriskofseriousadverseevents.InPhaseII,299patientswererandomlyassignedtoundergoeitherSTNorGPisurgeryandstimulation.At24months,patientshadsimilarimprovementinmotorfunctionaftereithersubthalamicorpallidalstimulation.Seriousadverseeventsoccurredin56%ofpatientsundergoingsubthalamicstimulationandin51%ofthoseundergoingpallidalstimulationwithnosignificantbetween-groupdifferences.ThebeneficialeffectsofDBSweresustainedover36months.Slightdeclinesinsomequality-of-lifesubscalesfollowinginitialgainsandgradualdeclineinneurocognitivefunctionslikelyreflectedunderlyingdiseaseprogressionandtheimportanceofnonmotorsymptomsindeterminingqualityof life. InordertoplanasuccessfulDBStreatment,factorsincludingpatientselection,targetidentification,skilledteamwork,post-surgicalcareandlong-termsupportneedtobeconsidered.
References1. Weaver FM, Follett K, Stern M, et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson
disease: a randomized controlled trial. JAMA 2009;301:63-73.2. Follett KA, Weaver FM, Stern M, et al. Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N Engl J Med
2010;362:2077-91.
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Psychogenic Non-epileptic Seizures
David G VosslerUniversity of Washington, Seattle, WA, United States
Psychogenicnon-epilepticseizures(PNES)arefoundinapproximately25to30%ofpatientsadmittedtoepilepsymonitoringunitsforseizurediagnosis.Formerlyknownaspseudoseizures,PNESareeventsofpsychologicalthatalters,orappearstoalter,neurologicfunctioninanepisodicmannercausingtransientmotorsigns,orsensory,autonomicorpsychicsymptoms,whichresemblethoseoccurringduringepilepticseizures.PNESareoftenincorrectlydiagnosedforyears.Thisleadstodelayinpropertreatment,over-utilisationofhealthcareresources,patientanxiety,andpotentialseriouscomplicationsfrominappropriatemedicaltreatments.OlderreportsclaimmanyPNESpatientsalsohaveepilepticseizures,butIandothershavefoundapproximately10%overlap.1Ifound41/52(79%)werefemalewithamedianageof38years.Kalogjera-SackellaresdescribestwomajorpsychologicalmechanismsforPNES:(I)Post-traumaticpseudoseizuresyndromeinwhichPNESdevelopduetoone/severaltraumaticexperiencesthatthepatientcannotadequatelyprocessorintegrategivenhis/herownpsychologicalresources,and(II)Developmentalpseudoseizuresyndrome.Inthefirstcategory,thetraumacanbesexual,minorphysical,parental,majorphysicalorso-calledchronictraumaticlifecourse.ExperiencedelectroencephalographersidentifyPNESusingclinicalsemiology.FeaturessuggestiveofPNESincludenon-physiologicornon-anatomicprogressionofsigns,out-of-phasebodymovements,closedeyes, thepresenceofstuffedanimalsinadultswithnormalintelligence,stuttering,2inappropriateemotions,andothers.
References1. Vossler DG. Nonepileptic seizures of physiologic origin. J Epilepsy 1995;8:1-10.2. Vossler DG, Haltiner AM, Schepp SK, et al. Ictal stuttering: a sign suggestive of psychogenic nonepileptic seizures. Neurology
2004;63:516-9.
Upcoming Antiepileptic Drugs: the United States Experience
David G VosslerUniversity of Washington, Seattle, WA, United States
Since1993, theUnitedStatesFood&DrugAdministration(FDA)hasapproved15newantiepilepticdrugs(AEDs).TheyearsofapprovalandtheAEDs,inorder,are1993felbamate,1994gabapentin,1995lamotrigine,1996fosphenytoin,1997topiramateandtiagabine,1999levetiracetam,2000oxcarbazepineandzonisamide,2005pregabalin,2008 lacosamideandrufinamide,2009vigabatrin,2010ACTHgel,2011ezogabine.Theuseoffelbamateislowduetoa1/4000riskofaplasticanaemiaorhepaticfailure.Vigabatrinhas lowusagedue to theriskofperipheralvisual field loss.Oxcarbazepine isused inmonotherapyforfocal-onsetseizures(FOS).ZonisamideisapprovedforadjunctivetherapyforadultswithFOS,but isalsousedaroundtheworldformyoclonicseizures.Tiagabine isaselectiveGABAreuptakeinhibitor(SGRI)usedinadjunctivetherapyforFOS.Fosphenytoinisthewater-solublepro-drugofphenytoin,fori.v.andi.m.use.Lacosamide,anaminoacid,hasanovelmechanismofaction:itenhancesslow inactivationofneuronal sodiumchannels.Thiscontrastswith theclassicAEDscarbamazepine,lamotrigine,oxcarbazepine,phenytoin,andrufinamidewhichenhancerapidinactivationofsodiumchannels.Lacosamideisavailableinivandoralforms.ItisapprovedforadjunctivetherapyforadultswithFOS,butresearchstudiesofgeneralised-onsetseizuresandchildrenareunderway.RufinamidehassomeefficacyinFOS,butisFDAapprovedonlyforLennox-Gastautsyndrome.ACTH(Acthargel) isapprovedforepilepticspasmsonly.AEDsawaitingFDAapprovalareeslicarbazepine,brivaracetam,perampanelandothers.
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Sleep and Epilepsy
Carl BazilCollege of Physicians and Surgeons at Columbia University, United States
Brainactivityduringsleepisverydifferentfromthatseenduringwakefulness.Duringnon-REMsleep,thebrainshowsmuchmoresynchronisedactivitythanduringwakefulnessorREMsleep.Sleepdisruptionisalsoknowntobeariskfactorforseizureexacerbation,andmanydrugsaffectsleep,sleepdisorders,andseizures.Itisthereforenotsurprisingthatepilepsyhasmanypotentialinteractionswithsleepandsleepdisorders.Theseincludedifferentialdiagnosis,timingofcertainseizuretypes,sleepdisruptionduetoseizures,andthefrequencyandtreatmentofcoexistingsleepdisorders. Fromaclinicalstandpoint,bothseizuresandsleepdisorderstypicallyoccuroutsideofamedicalsetting.Theyarenotwitnessedby the treatingphysician, thereforediagnosis reliesheavilyondescriptionsfrompatientandonlookers,whichcanbeincompleteatbestandmisleadingatworst.Asbothparasomniasandnocturnalseizuresinvolvealterationinbehaviourand/orconsciousness,thesecanbedifficulttodistinguish.Prominentexamplesincludenocturnalfrontallobeepilepsy,disordersofarousal,andcataplexy.Thusdifferentialdiagnosisofnocturnalseizuresthereforeoftenincludessleepdisorders,andviceversa. Certainepilepsysyndromesareprofoundlyaffectedbythesleep-wakestate.Prominentexamplesincludejuvenilemyoclonicepilepsy,nocturnalfrontallobeepilepsy,andbenignrolandicepilepsy.Somepartialseizuresalsohavearelationshipwithsleep;frontallobeseizuresforexampletendtoarisemorefrequentlyfromsleep.Theseobservationscanhaveimplicationsfordiagnosisandtreatment. Nocturnalseizuresdisruptsleep,evenwhenquitebrief.Thisdisruptioncanberesponsibleforthedifficulty indaytimefunctioningmanypatientshavefollowingseizures.Assleepdisruptioncanincreasetheriskofseizures,thiscansetupacycleofseizures,consequentsleepdisruption,andfurtherintractabilityofseizures. Sleepdisordersarecommoninthegeneralpopulation,andmanyoccurevenmorefrequentlyinpatientswithepilepsyincludinginsomnia,obstructivesleepapnoea,periodic limbmovements,andrestless legssyndrome.Theseareoftenunrecognised,butwhenuntreatedcanalsocontributetodecreasedfunctioningandtointractabilityofepilepsy. Mostpatientswithepilepsytakeanticonvulsantdrugs.Thesehavethepotentialtoaltersleepthroughimprovement innocturnalseizures; througheffects(positiveornegative)oncoexistingdepression,anxiety,orsleepdisorders;andthroughindependenteffectsonsleep. Qualitysleepisknowntobeimportantintheconsolidationofmanykindsofmemory,thereforesleepdisruption(duetosleepdisorders,seizures,ormedication)cancontributetothememoryproblemssooftendescribedbypeoplewithepilepsy.Vigilanceforpossibleconcurrentsleepdisordersisimportantparticularlywhenpatientshaveunexplainedsomnolence,memoryproblems,orcontinuedseizuresespecially ifseizuresarepredominantlynocturnal.Overall,knowledgeofthe interactionsbetweenepilepsyandsleepdisordersisessentialtotheoptimalcareofpatientswithepilepsy.
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Psychiatric Issues in Epileptic Disorders
Joyce LamDepartment of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR
Overthepastdecades,increasingliteraturessuggestedthatepilepticdisorderhascomplexrelationshipswithotherneurological,cognitive,psychiatricandbehaviouraldisorders.Epilepsyisnowconceptualisedasaspectrumcondition,as theco-morbidconditionshavebeendemonstratedtosharecommonphenotypesandaetiologicalfactorswithepilepsy.Psychiatricillnesses,suchaspsychosis,anddepression,havebeendemonstratedtobehighlyprevalentamongpatientswithepilepsy.Forexample,cross-sectionalstudiesfoundthattheprevalenceofdepressioninpatientswithepilepsyrangedfrom10%to30%incommunity-basedsamplesandevenmountedupto50%inclinicpopulations.Insteadofsimplyapsychologicalreactiontochronicillness,studiesfocusingonthetemporalassociationsestablishedthatdepressionisariskfactorforincidentunprovokedseizures,suggestinganunderlyingbi-directionalrelationship.Psychiatricdisordersarealsofoundtosharegeneticorneurochemicalbasiswithepilepsy.The“iatrogenic”effect, includingtheuseofpsychotropics,anticonvulsantsandsurgicaltreatmentofepilepsy,furthercomplicatestherelationships. Thispresentationwill focusonthepsychiatricandcognitiveco-morbiditiesofepilepticdisorder,illustratingtheclinicalepidemiology,aetiologicalaspects,treatmentimpactandtheco-morbiditiesinspecialclinicalpopulations.
Basic Neurogenetics: What Clinical Neurologists Need to Know
KY MokDepartment of Molecular Neuroscience, UCL Institute of Neurology, United Kingdom
Atbedside,understandingthegenetictransmissionandtheroleinpathomechanismis important.Itiscrucialnotonlyinmanagementofthepatient.Theimportanceextendstothecareoftheirfamilymembersandmayhavesignificantsocial implication.Atmacrolevel,understandingthegeneticsofdiseaseprovideusaviewonthepathophysiology. Syndromescausedbychromosomal insertionsanddeletionsarewelldocumented.Majorityofthesepatientsmaynotbeunderthecareofneurologists.Mendelianormonogenicdisorderisprobablythemostwell-knowntypeofgeneticmechanismknowntoclinicianbutit isnottheonlyone.Manyneurodegenerativediseases,egParkinson’sdisease,motorneurondiseasehaveasmallportioncausedbymonogenicdisorder.Majorityaremulti-factorial,iecomplexdiseasesorcommondisease.Thispatientgroupcontributesthebulkofclinicalload.Theapparentlysameclinicalentitycanbecausedbyasinglemutationwithverylargeeffectsizeoramultipleoffactorswithintermediate/smalleffectsize. Genotypephenotypecorrelationcanbedifficult todissect.Monogenicdisorderscanhavethephenotypealteredbyotherfactors.Sexandthespecialgenetictransmissionofmitochondriaareamongthesefactors.Furthermore,differentmutationswithinthesamegenemayhavedifferentphenotypeandmodeofinheritance. Itisabsolutelytruethatpeoplefromdifferentethnicoriginhavemorefeaturesincommonthanthedifference.Thereistheothersideofthecoin,iedifferenceindiseasepatternisnolessgenuinethanthecommonality.Thisisparticularimportantintheapproachtogeneticdisorders,bydefinition,causedbythegeneticmakeupoftheindividual.Thedifferentialmakeupcontributestothedifferenceinethnicgroupandatthesametime,thediseasespectrum.
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Molecular Neurogenetics: Tools and Methods
Liz YP YuenDepartment of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR
Inthepost-genomicera,thenumberofcausativegenesidentifiedforneurologicaldisordersisincreasinginaveryrapidpace.Thesediscoveriesareaccompaniedbyaproliferationofmolecularmethodologiesthatcanbeappliedinaclinicallaboratoryforaccuratedetectionofmutationsinthesegenes. Thefollowingfactorsthatdeterminethechoiceofmolecularmethodsforaparticulardiseasewillbediscussed.1. Mutationtypes:smallmutations(egsinglebasesubstitutions,smalldeletions/insertions,splicesite
mutations,etc),trinucleotiderepeatsandlargemutations(egexonicorwholegenedeletion,largeinsertion,complexrearrangements)
2. Geneticandallelicheterogeneity3. ProblemsspecifictomitochondrialDNA Anoverviewofcommonlyusedmolecularmethodsthatareusedinclinical laboratorieswillbepresented.1. Numberingoftrinucleotiderepeats2. Mutationscanningversusdirectsequencing3. Methodsfordetectionoflargemutations4. Methodsonthehorizon:nextgenerationsequencing Interpretationofmolecular findingsremainsoneof themostdifficult tasks ingenetic testing.Determinationofpathogenicityofanovelvariantmaynotbestraightforward.Commoninterpretationproblemsandpotentialsolutionswillbediscussed.
Advanced Neurogenetics: Frontiers in Research
KY MokDepartment of Molecular Neuroscience, UCL Institute of Neurology, United Kingdom
RecentadvancesinParkinson’sdiseaseandmotorneurondiseasewillbeusedasillustration.Discussionswill includeunderstandingdiseasemechanismsbasedon thestudyresultsandpracticalclinicalimplicationsinthenewtechnologies.
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S 19Current Approach for Chronic Migraine Management
SJ WangThe Neurological Institute, Taipei Veterans General Hospital; National Yang-Ming University School of Medicine, Taipei, Taiwan
Chronicdailyheadache(CDH)isdefinedisdefinedas≥15headachedayspermonthfor≥3months.Chronicmigraine (CM) isclassifiedasadisablingcomplicationofmigrainewithoutauraby theInternationalClassificationofHeadacheDisorders,2ndedition(ICHD-2),2004.ItisonesubtypeofCDHandisdefinedas≥15headachedayspermonth,≥8migrainedaysfor≥3monthsintherevisedICHD-2criteria,2006.Thepopulationprevalenceisestimatedtobeabout1.5to2%.ItisthecommondiagnosticentityinheadacheclinicsandmanypatientswithCMoverusedabortivetreatmentincludingergotamine,triptans,analgesicsornarcotics.EmergingevidencesuggeststhatepisodicmigraineandCMdiffer,notjustindegree,butalsoinkind.Theexactunderlyingmechanismisnotclearbutsomestudiessuggestcorticalhyper-excitabilityordysinhibition.PatientswithCMhaveworsesocioeconomicstatus,reducedhealth-relatedqualityoflife,increasedheadache-relatedburdenincludingimpairmentinoccupational,social,andfamilyfunctioning,andgreaterpsychiatricandmedicalcomorbiditiesincomparisonwithepisodicmigraine. Adetailedhistorytakingandneurologicalexaminationareimportantforthediagnosisofchronicmigraine.Secondaryheadachedisordersshouldbeexcludedbeforemakingthediagnosis.Routineneuroimagingstudiesarenotevidence-based.Aheadachediaryisbothhelpfulfordiagnosisandfollow-up.Psychiatriccomorbidityespeciallydepressiveandanxietydisordersareverycommoninpatientswithchronicmigraine.Psychiatristsshouldplayamajorroleinthemulti-disciplinarytreatmentteamforbothpsychiatricconsultationandtreatment.Withdrawalofoverusedabortivetreatmenthasbeensuggestedforthosewithmedicationoveruseheadache.However,whetherprophylacticagentsaregivenatthesametimeorafterwithdrawaldonothaveconclusions. PatientswithCMusuallyareexcludedfrommigraineprophylaxistrialsbecausetheyareconsideredtobetoohighlydisabledandtreatmentresistant.However,thereareasubstantialamountofthesepatients,andindeed,theyarethepatientswhoimperativelyrequireeffective,safe,andwell-toleratedheadacheprophylactictherapy.Uptonow,onlyonabotulinumtoxinAandtopiramatehadthebestevidenceforchronicmigraine. The largetrialPhase3ResearchEvaluatingMigraineProphylaxisTherapy(PREEMPT),consistingof twostudies(PREEMPT1andPREEMPT2),aimstoevaluatetheefficacy,safety,andtolerabilityofonabotulinumtoxinAusinga fixed-site, fixed-dose injectionprotocol (in total155Uover31sites)andanoptionaladditionof40U‘follow-the-pain’paradigm.PREEMPT1and2demonstrated thatonabotulinumtoxinAisaneffectiveprophylactictreatmentforCMinreducingheadachedayspermonthastheprimaryoutcomeandmostsecondaryheadachesymptommeasures.Mostadverseevents(AEs)weremildtomoderateinseverity,andfewpatientsdiscontinuedthetrial(onabotulinumtoxinA,3.8%;placebo,1.2%)duetoAE.TworandomisedcontrolledstudiesconductedintheUnitedStatesandEurope,respectively,demonstratedthattopiramateiseffectiveasheadacheprophylaxis inCM.However,thetherapeuticgainofthesetwotreatmentagentsalsowasmodestdespitedifferentstudyend-points.ThemoderateeffectsizesofthesestudiespointedouttherefractorinessofCMandapotentialneedofcombinationtherapyinfuturetrials.Ofnote,bothtopiramateandonabotulinumtoxinAshowedsimilarefficacyintreatmentofCMbetweenthosewithandwithoutmedicationoveruse.
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S 20Updated Guidelines for Treatment of Neuropathic Pain
PP ChenDepartment of Anaesthesia, Alice Ho Miu Ling Nethersole Hospital / North District Hospital, Hong Kong SAR
Severalrecommendationsregardingthetreatmentofneuropathicpainhavebeenpublishedintheliterature,mostlyunder theauspicesofmajorprofessionalandacademicorganisations inNorthAmerica,LatinAmericaandEurope.1-6Overall, therearefewdifferencesamongthepharmacologicalrecommendationsfortreatingneuropathicpain.Inmost,tricyclicantidepressantsandcalciumchannelα2-δ ligandsareoftenregardedasfirst-linetherapy,whileselectiveserotoninnoradrenalinereuptakeinhibitorsandtopicallignocaineareconsideredfirst-orsecond-linetreatments.Tramadolandopioidanalgesicsareregardedassecond-orthird-linetreatment.Afewguidelinessuggestedcombinationtherapywhenmonotherapyisunsatisfactory.5-7 Despite these guidelines providing evidence-based recommendations for the treatment ofneuropathicpain,studieshaveshownthatsuccessfultreatmentsofneuropathicpainatbestprovideonlypartialpainreliefforabouthalfofthosetreated.8Inpart,thisoutcomeisduetothelimitationsintheexistingclinicalevidenceandresearchinneuropathicpain.Recentrecommendationssuggestamorerationalstrategyforthetreatmentofneuropathicpain,includingthefollowing:(1)carefulassessmenttoestablishadiagnosis,(2)considerthesymptomswhichmaysuggesttheunderlyingmechanisms,(3) identifyco-morbiditiesthataffectthetreatment,(4)establisharealisticexpectationwithpatient,(5)selecttheappropriatetreatment—first-,second-,third-linedrugs,avoiddrugwithsignificantadverse
effects,considerdrugthatwillalsoimproveothercomorbidities,egsleepandmood,(6)measurefunctionalandHRQOLoutcomesotherthanpain,(7)reassessthepatientaftertrialperiodoftherapy,(8)considercombinationtreatmentifmonotherapyfailed,(9)refertopainspecialistsiftherapyfailedandifmultidisciplinarymanagementisdeemednecessary. Othernewertreatmentoptionsarealsodiscussedinthelecture.
References1. Dworkin RH, O’Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based
recommendations. Pain 2007;132:237-51.2. Moulin DE, Clark AJ, Gilron I, et al. Pharmacological management of chronic neuropathic pain—consensus statement and
guidelines from the Canadian Pain Society. Pain Res Manag 2007;12:13-21.3. Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. 4. Algorithm for neuropathic pain treatment: an evidence based
proposal. Pain 2005;118:289-305.4. Attal N, Cruccu G, Haanpää M, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol
2006;13:1153-69.5. Attal N, Cruccu G, Baron R, et a. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J
Neurol 2010;17:1113-e88.6. Tan T, Barry P, Reken S, Baker M; Guideline Development Group. Pharmacological management of neuropathic pain in non-
specialist settings: summary of NICE guidance. BMJ 2010;340:c1079.7. Acevedo JC, Amaya A, Casasola Ode L, et al. Guidelines for the diagnosis and management of neuropathic pain: consensus of a
group of Latin American experts. J Pain Palliat Care Pharmacother 2009;23:161-81.8. Dworkin RH, O’Connor AB, Audette J, et al. Recommendations for the pharmacological management of neuropathic pain: an
overview and literature update. Mayo Clin Proc 2010;85(3 Suppl): S3-14.
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S 21Trigeminal Autonomic Cephalalgias
TH TsoiDepartment of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR
Trigeminalautonomiccephalalgias(TACs)areagroupofprimaryheadachedisorderscharacterisedbyunilateraltrigeminaldistributionpaininassociationwithipsilateralcranialautonomicfeatures.TACsincludeclusterheadache,paroxysmalhemicraniaandshort-lastingunilateralneuralgiformheadacheattackswithconjunctivalinjectionandtearing(SUNCTsyndrome),whichareallshort-lastingheadaches.Theseshort-lastingheadacheswithautonomic featuresarecharacterisedbyanexusofactivationbetweentrigeminalafferents(givingrisetopain)andcranialparasympatheticefferents(givingrisetoautonomicfeatures). In1997,GoadsbyandLiptonfirstproposedthattheseheadachesshouldbeclassifiedtogetherasa linkedpathophysiology is thehallmarkof thesesyndromesandsuggestedthetermtrigeminal-autonomiccephalgias(TACs)thoughitdoesnot implyall theseheadacheshaveacommonpathogenesis.Theirproposalwasadoptedby the InternationalHeadacheSociety.TheheadachesaregroupedintoChapter3ofthe2ndeditionofInternationalClassificationofHeadacheDisorders(ICHD-II).ThenosologyofhemicraniacontinuaisunclearandisplacedintheChapter4oftheICHD-II.Ithasacontinuouspainwithexacerbationthatcanincludecranialautonomicsymptomsaspartofthephenotype. Cranialparasympatheticactivation(lacrimation,rhinorrhoea,nasalcongestionandeye-lidoedema)andsympathetichypofunction(ptosisandmiosis)arethesignaturefeaturesofallTACsandhemicraniacontinua.Despitetheirsimilarities,thesedisordersdifferintheirclinicalmanifestationsandresponsetotherapy,thusitisimportanttorecognisethem.Theimportanceofdiagnosingthesesyndromesresidesintheirexcellentbuthighlyselectiveresponsetotreatment.Trigeminal-autonomicreflexisbelievedtobeimplicatedinthepathophysiologyofTACsandithasbeenshowninanimalexperimentsthatstimulationoftrigeminalefferentscanresult incranialautonomicoutflow.PETandfunctionalMRIstudieshavedemonstratedipsilateralhypothalamicactivationinclusterheadacheandSUNCTsyndrome,suggestinganimportantroleofhypothalamicabnormalityinthesetwoTACs.TheimplicationofhypothalamusinpathogenesisofTACsisfurthersupportedbythesuccessoftreatmentwithhypothalamicstimulationinpatientswithdrug-resistantchronicclusterheadache. Inthepastfewyears,manycasesofsecondaryTACorTAC-likesyndromehavebeenaddedintheliterature.Thereareno‘typical’warningsignsorsymptoms.NeuroimagingshouldbeconsideredinallpatientswithTACorTAC-likesyndromesbeforemakingthediagnosisofaprimaryheadache.
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S 22Anticoagulation for Prevention of Stroke in Patients with Atrial Fibrillation
Jaseong KooDepartment of Neurology, Stroke Center, Seoul St. Mary's Hospital, Catholic University of Korea, Korea
Atrial fibrillation (AF) is themostcommoncardiac rhythmdisorder.Comparedwith thegeneralpopulation,peoplewithAFhavea5-foldincreasedriskofstroke.AspirinandvitaminKantagonists(VKAs)areusedforpreventionofAF-relatedstroke.Comparedtoplacebo,aspirinreducesthestrokeriskby22%.VKAsreducethestrokeriskby68%comparedtoplaceboand52%comparedtoaspirin.VKAsarethereforecurrentlyrecommendedasfirst-linetherapyinpatientswithAFandamoderateorhighriskforstroke.However,treatmentwithVKAsisoftenpoorlymanagedandunderusedbecauseofseveraldrawbacks.Themajordrawbacksareunpredictableinteractionswithfoodandotherdrugs,theinconvenienceofINRmonitoring,theneedfordoseadjustment,andtheperceivedriskofbleeding. Recently,threenewnoveloralanticoagulants(dabigatran,rivaroxaban,apixaban)weredeveloped.TheneworalanticoagulantsallsharenotableadvantagesovertheVKAs,includingpredictableanticoagulanteffectsatfixeddoses,limiteddrugandfoodinteractions,noneedforroutinebloodlevelmonitoring,andabroadertherapeuticwindow.Currently,datafromfourlargeclinicaltrials(3warfarintrials[RE-LY,ROCKET-AF,ARISTOTLE]and1aspirin-controlledtrials[AVERROS])ontheefficacyandsafetyoftheseagentsareavailable. DabigatranisadirectthrombininhibitorandwastestedintheRE-LYtrial.RE-LYisarandomisednon-inferioritystudywithanopentreatmentandblindedendpointassessment.InRE-LY,18113patientswhohadAFandariskforstrokewererandomisedtoreceiveeitherafixeddoseof110or150mgdabigatrantwicedailyordose-adjustedwarfarin(INR2-3).Atadoseof110mgtwicedaily,dabigatranwasassociatedwithasimilarrateofstrokeandsystemicembolismtowarfarin,andasignificantlylowerrateofmajorbleedingthanwarfarin.Atthehigherdoseof150mgtwicedaily,therateofstrokeandsystemicembolismwassignificantlylowerthanwithwarfarin,buttherateofmajorbleedingwassimilartothatassociatedwithwarfarin. RivaroxabanisadirectfactorXainhibitorandwastestedintheROCKET-AFstudy.ROCKET-AFisadouble-blindnon-inferioritystudywhichrandomised14264patientswithAFwhowereat increasedriskforstroketoreceiveeitherrivaroxaban20mgoncedailyordose-adjustedwarfarin(INR2-3). Intheprimaryanalysis,rivaroxabanwasassociatedwithasignificantlylowerrateofstrokeandsystemicembolismthanwarfarin.Intheintention-to-treatanalysis,rivaroxabanwasnon-inferiortowarfarinforpreventionofstrokeorsystemicembolism.Theratesofmajorandnon-majorclinicallyrelevantbleedingweresimilarbetweenthegroupswithasignificantlylowerrateofintracranialhaemorrhageandfatalbleedingintherivaroxabangroup. ApixabanisananotherdirectXainhibitorandwastestedintheAVERROSandARISTOTLEstudies.AVERROSisarandomiseddouble-blindstudytoinvestigatethesuperiorityofapixaban5mgtwicedailycomparedtoaspirin(81-324mgperday)in5599patientswithAFandariskforstrokebutarenotsuitablefororareunwillingtoreceiveVKAs.Apixabanwasassociatedwithasignificantlylowerrateofstrokeandsystemicembolismandasimilarrateofmajorbleedingcomparedwithaspirin.ARISTOTLEisadouble-blindnon-inferioritywhichrandomised18201patientswithAFandatleastoneadditionalriskfactorforstroketoreceiveeitherapixaban5mgtwicedailyordose-adjustedwarfarin(INR2-3).Theratesofstrokeorsystemicembolismandmajorbleedingweresignificantlylowerwithapixabanthanwithwarfarin. It isnotappropriate tocomparedirectly theefficacyandsafetyof theneworalanticoagulantsbecausethestudydesignandthestudypopulationweredifferentamongtheclinicalstudies.However,theROCKET-AFstudyismoreexcitingtostrokecliniciansbecause50%ofthestudypopulationhadpriorstrokewithTIAwhichmeansthattheyareahigher-riskpopulationwhiletheRE-LYstudyrecruitedabout20%oftheirpopulationwhohadpriorstrokewithTIA,asdidARISTOTLEandAVERROES.Aftermanyyearsofwrestlingwiththedifficultiesofwarfarin,itseemsquitelikelythatcliniciansnowhaveanembarrassmentofrichesinnew-generationoralanticoagulantsforAF.
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Surgical Outcomes from Revascularisation Surgery for Moyamoya Disease: Experience in Tuen Mun Hospital, Hong Kong
KF Fok1, WL Poon2, YC Wong2, Florence Kwok3, Dawson Fong1
1 Department of Neurosurgery, Tuen Mun Hospital, Hong Kong SAR2 Department of Radiology, Tuen Mun Hospital, Hong Kong SAR3 Psycho-behavioural Unit, Tuen Mun Hospital, Hong Kong SAR
Moyamoyadisease(MMD)isararecerebrovasculardiseasecharacterisedbystenosisandocclusionofthebilateralinternalcarotidarteriesresultinginthecharacteristicdevelopmentofanabnormalnetworkintheareasofthearterialstenosis.Variousrevascularisationprocedureshavebeenusedinthetreatmentofthisgroupofpatients.Tostudytheclinicalcharacteristicsandlong-termoutcomesinthetreatmentofMMDinHongKong,weanalysedourresultatDepartmentofNeurosurgery,TuenMunHospital,HongKong. Dataobtainedin23patientswithMMD(meanage31years,range5-64years)managedinTuenMunHospitalbetween1995and2011wereanalysed.Nineofthemareinpaediatricagerange(age<18years).Nineteenpatientspresentedwithacutesymptom, threewithrecurrent transient ischaemicattack(TIA)andonewasdetectedincidentally.Amongthosewithacutepresentation,almosthalfofthem(52%)demonstratedacutecerebralhaemorrhageinneuroimaging,therestshowedcerebralinfarction.Only17%oftheseMMDpatientsshowednocerebralinsultintheneuroimagingonpresentation.ThediagnosiswasestablishedclinicallyandalsoconfirmedbyMRIandcerebralangiograminallpatients.Preoperativecerebralangiographyshowedthatthepatientsareinvariousstagesofdisease,butthemajorityofthem(20outof38hemispheres)wereinstage3ofSuzukiclassification.RecentlywealsoincludedCTperfusionstudy(CTP)withacetazolaminechallengeandneuropsychologicalassessmentinourpre-surgicalassessmentprotocol. Of the 23 patients, 18 received microsurgical revascularisation procedures. Seven patientsunderwentunilateraland11patientsbilateral revascularisation(30 treatedhemispheres included1repeatedrevascularisation).Thesurgicalprocedures includedencephaloduroarteriosynangiosis(EDAS)in15,encephalodurogaleoarteriosynangiosis(EDGAS)in3,combinedEDASandEDGASin9,encephaloduroarteriomyosynangiosis(EDAMS)in1,Burrholein1andSTA-MCAbypasswithEDGASin1patient.Therewasnomortalityinourseriesbutweexperiencedtwo(6.7%)postoperativecerebralinfarctiondevelopedoutof30hemispheres treated.Bothof themshowedworsenneurologybutimprovedwithconservativemanagement. Themeanfollow-upperiodforthese18patientsunderwentrevascularisationprocedurewas75.2months(range,1-154months).Postoperativecerebralangiogramperformedshowed90%offrontalgraftdevelopedcollateralformationachievinggradeAorBinMatsushimagradingscale(synangiosismorethanone-thirdfillingofanteriorcerebralarteryterritory),while55%ofEDASgraftshowedsimilargrading inmiddlecerebralartery territories.Duringthis follow-upperiod,onepatientdevelopedrecurrenthaemorrhage12yearsafterEDASprocedure.Nopatientinischaemicgroupdevelopednewinfarctonrevascularisedhemisphereinourpatientseries.Functionally,66%(12patients)demonstratedimprovementinmodifiedRankinScale(mRS)by1pointormore.TherestofthegroupshowedthesamemRSasinpreoperativestatus. Inconclusion,revascularisationsurgery inpatientswithMMDcarriesa lowrisk; it iseffectiveatpreventingfutureischaemiceventandimprovesqualityoflife.
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32 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
Surgical Management of Moyamoya Disease
KC WangSeoul National University Hospital, Korea
Moyamoyadisease(MMD)isthemostcommonpaediatriccerebrovasculardiseaseofsurgicalconcern. MMD with symptoms such as TIA, infarction, seizure, headache/orbital pain, haemorrhageis candidate of surgical treatment. For paediatric patients, indirect revascularisation methods,includingencephaloduroarteriosynangiosis (EDAS)usingsuperficial temporaloroccipitalarteries,encephalomyosynangiosis(EMS),encephalogaleo(periosteo)synangiosis(EGS,EGPS),multipleburrholetrephinationwithinsertionofgaleoperiostealflap,andtheircombination,arerecommended.Inadultcases,directrevascularisationmethods,suchassuperficialtemporalartery-middlecerebralartery(STA-MCA)anastomosis,with/withoutindirectrevascularisationmethods,arefrequentlyused.Directsurgeryismoreuseful inadultpatientswithMMDbecausetheindirectsurgery iseffectiveforrecruitmentofcollateralsonlyin40to50%ofadults, incontrasttothepaediatricpatientswhoshownearly100%improvementofCBFifextensiveinfarctionisabsent.Directanastomosisisfrequentlynotfeasibleinchildrenbecauseofsmallsizeandfragilityofthevessels. Accordingtotheresultsofhaemodynamicstudies,suchascerebralangiography,SPECT,PETandperfusionMRI,thebrainareasforrevascularisationareselected.Almostalwaysbothmotorcortexareasareincluded.WerecommendadditionofbifrontalEGS/EGPSforrevascularisationofanteriorcerebralartery(ACA)territories.Insomepatientswithischaemiaintheposteriorcerebralartery(PCA)territory,occipitalartery isusedforEDAS.SomecasesofunilateralMMD(probableMMD)aretreatedwithunilateralsurgery.Because25to35%ofthemshowprogressiontothebilateraldisease,theyshouldbemonitored.Stagedoperationsaredesignedaccordingtothepatient’ssymptom,haemodynamicdataandtherateofdiseaseprogression. Regardlessofthesurgicalmethod,postoperativegoodcollateralformationisfoundin80to90%ofthepatients.Patientswithpreoperativeextensivecerebralinfarctionshowpoorcollateralformationaftersurgery. Perioperative ischaemiccomplicationsarenotrare.Becauseof lackofvascularreserve inthesepatients,theyarevulnerabletoischaemiacausedbytheintraoperativeandpostoperativehypotension,anaemia,hypovolemiaandhypocarbia.CarefulpreservationofthecollateralchannelsandmeticulousmonitoringofthehaemodynamicfactorsareessentialfortheperioperativemanagementofMMD.Mostofthepostoperativeischaemiccomplicationsareevidentduringthefirstpostoperativeweek. Inpatientswithdirectrevascularisation,suddenincreaseofperfusionpressureintheischaemicbrainmaycausebraindamagebytemporaryhyperperfusion,especiallyinpatientswithpreoperativeprolongedprofoundischaemia. MMDpatientsyoungerthan3yearsfrequentlyshowrapidprogressionofdiseasetowidespreadcerebral infarction.Theoutcomemaybeadverselyaffectedbythepreoperativebilateral ischaemicdamage inthisage-group.Eventhoughtheyaremorevulnerabletoperioperative ischaemicbraindamagethanolderchildren,theoverallmanagementoutcomeisbetterincaseswithearlysurgery. ThereisnosolidevidencethatsurgeryisbeneficialincasesofMMDwithhaemorrhage,althoughithasareasonabletheoreticalbasis.Surgeryisfrequentlyrecommendedforthesepatients.
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S 25Mechanical Thrombectomy in Ischaemic Stroke: a Look at the Toolbox
Ferdinand HuiCleveland Clinic Foundation, United States
SincetheintroductionoftheMercifamilyofclotretrieversanddisruptiondevice,therehasbeenablossominginthenumberofdevicesdesignedtore-establishflowinthesettingofischaemicstrokerangingfromthrombectomydevices,aspirationdevices,stents,andstent-retrieverswithmanymoretocome.Efficacyandeaseofuseareprobablytheprimarydeterminantsofphysicianutilisation. ThispresentationwillreviewthemajordevicesavailableinNorthAmerica,EuropeandHongKong,compareandcontrastthemechanismsofaction,easeofusecharacteristics,andreviewsomeofthetipsandtricksassociatedwiththedevicesinquestion. Reviewwillalsoincludemajorintra-arterialtrialsandforthcomingtrialsthatwillbeofinterestinthefurtherdevelopmentofintra-arterialstrategies.
34 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
Medical Management of Intracranial Stenosis
Kazunori ToyodaDepartment of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
Atheroscleroticstenosisofintracranial largearteriesisanimportantstrokemechanismespeciallyforAsianpopulations.Intracranialatherosclerosiscausesstrokeduetothebranchocclusion,arterytoarteryembolism,andboth.Theintracranialstenosisisnotstatic,andmayprogressorregressinarelativelyshortperiodof time.Progressivestenosisof intracranialarteries is relatedto thedevelopmentofischaemicevents. InJapan,weoftenuseintravenousargatroban,adirectthrombininhibitor,aloneorwithantiplateletagents as acute antithrombotic therapy for atherothrombotic stroke patients with intracranialatherosclerosis.Arationaleofargatrobanuse inacuteatherothromboticstroke isderivedfromadomestictrialresults,but itsefficacyfor intracranialatherosclerosis isnotscientificallyestablished.Asanotherintravenousanticoagulant,theFISS-trisstudy1failedtoshowasignificantbenefitof low-molecular-weightheparinoveraspirininpatientswithacutestroke(<48h)withlargearteryocclusivedisease(mostlyintracranial).Forsubacutestroke/TIApatients(<90days)withintracranialarterystenosis,theWASIDtrial2showedhigherratesofadverseeventsandnobenefitofwarfarin(INR2.0-3.0)overaspirin.Thus,anticoagulationisnotaworld-standardstrategyforintracranialatherosclerosis. Dualantiplatelet therapy isapromisingchoice for intracranialatherosclerosis, although thecombinationofaspirinandthienopiridineisnotroutinelyrecommendedforgeneralstrokepatientsduetoincreaseinbleedingrisk.IntheCLAIRtrial,3combinationofclopidogrelwithaspirinwasmoreeffectivethanaspirinaloneinreducingmicroembolicsignalsinacutestroke/TIApatients(<7days)withpredominantlyintracranialarterystenosis.ProgressionofM1orbasilarstenosisduring6monthsafterstroke(<2weeks)wassignificantlylowerinpatientstreatedwithcilostazolplusaspirinthanthosetreatedwithaspirinaloneintheTOSS.4Recently,TOSS-25showedsimilarefficacyofpreventingprogressionofintracranialarterystenosisandnewischaemiclesionsbetweendualtherapyusingcilostazolandaspirinandthetherapyusingclopidogrelandaspirininacutestrokepatients(<2weeks). Statin,pioglitazone,andsomeantihypertensiveagentsareotherpromisingmedicaloptionforintracranialatherosclerosis; their therapeuticpowershouldbeproperlyevaluated.Angioplastyandstentingforsymptomatic intracranialarterystenosisremainscontroversial.Therecruitmentof theSAMMPRIStrialwasprematurelyterminatedbecauseofthehigher30-daystrokeanddeathratesaftertreatmentwithintracranialangioplastycombinedwithstentingusingtheGateway-Wingspansystemthanthoseafteraggressivemedicaltherapyalone.6Furtherstudies,andespeciallystudiesfromAsia,arerequiredtoobtainthebesttherapeuticstrategyinpatientswithintracranialatherosclerosis.
References1. Wong KS, Chen C, Ng PW, et al. Low-molecular-weight heparin compared with aspirin for the treatment of acute ischaemic
stroke in Asian patients with large artery occlusive disease: a randomised study. Lancet Neurol 2007;6:407-13.2. Chimowitz MI, Lynn MJ, HOwlett-Smith H, et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial
stenosis. N Engl J Med 2005;352:1305-16.3. Wong KS, Chen C, Fu J, et al. Clopidogrel plus aspirin versus aspirin alone for reducing embolisation in patients with acute
symptomatic cerebral or carotid artery stenosis (CLAIR study): a randomised, open-label, blinded-endpoint trial. Lancet Neurol 2010;9:489-97.
4. Kwon SU, Cho YJ, Koo JS, et al. Cilostazol prevents the progression of the symptomatic intracranial arterial stenosis: the multicenter double-blind placebo-controlled trial of cilostazol in symptomatic intracranial arterial stenosis. Stroke 2005;36:782-6.
5. Kwon SU, Hong KS, Kang DW, et al. Efficacy and Safety of Combination Antiplatelet Therapies in Patients With Symptomatic Intracranial Atherosclerotic Stenosis. Stroke 2011 Jul 28. Epub ahead of print.
6. Leung TW, Yu SC, Wong KS. Have medical therapy and stenting been fairly compared? A repercussion upon termination of recruitment in the SAMMPRIS trial. Int J Stroke 201;6:312-4.
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Off-label Use of Rituximab in Refractory Neurological Autoimmune Diseases—Experiences of a Regional Teaching Hospital in Hong Kong
Vincent HL Ip, Alexander YL Lau, Anne YY Chan, Lisa WC Au, Florence SY Fan, Nick NC Ng, Edward HC Wong, Yannie OY Soo, Vincent CT Mok, Thomas WH Leung, Lawrence KS WongDivision of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR
Background:Rituximabisachimericmouse-humanmonoclonalantibodyagainsttheproteinCD20whichispresentonthesurfaceofallB-celllineagesexceptforthestemcells,pro-Bcellsandnormalplasmacells.BecauseoftheincreasingawarenessoftheroleofB-cellinthepathogenesisofvariousautoimmuneneurologicaldiseases,thereareincreasingoff-labelprescriptionsofrituximabfortheseseriousdiseasessuchasrelapsingmultiplesclerosis(MS),neuromyelitisoptica(NMO)andmyastheniagravis(MG).However,therearenorandomisedcontrolledtrialsinstudyingtheseoff-labelusesofrituximab.Wereporteightcaseswhereoff-labeluseofrituximabinseveralrefractoryneurologicalconditionsatthePrinceofWalesHospitalinHongKong,atertiaryteachinghospitalofTheChineseUniversityofHongKong.Methods:Patientswhohavereceivedrituximabasanoff-labelindicationwereidentifiedfromtheMSregistries,aswellasfromrecallbyindividualphysicianwhohasuseditinotherconditionssuchasNMOandMG.Datawereretrievedretrospectivelyfromtheelectronicpatientrecord(ePR)betweenAugust2008andJuly2011.Informationincludingthediagnosis,clinicalpresentations,concurrentmedicationsandprevioustreatments,dosagesandregimensofrituximabused,side-effectsexperiencedandclinicalprogresswererecorded.Results:Eightpatientsreceivedrituximabasoff-labeluseduringtheperiodaudited.IndicationsincludedprimaryprogressiveMS,NMOandMG.Twoofthecasesaremalepatients.Rituximabwasusedmainlyasmaintenancetherapyinallcasesexceptinonecaseinwhichitwasusedasanacuteinductiontherapyinoneepisode.Themostcommonprescribeddosageis2000mgpercoursewithregimenof1000mggivenbi-weekly.Coursesoftreatmentgivenrangedfrom1to5,andthetimeintervalbetweencoursesrangedfrom5to11months.Therewerenoreportedseriousinfusionreactionandnonotableadverseeventsassociatedwithrituximabuseduringtheaboveauditedperiod.Conclusions:Overall,theoff-labeluseofrituximabappearstobesafeandpromisingresultscanbeseenincasesofNMOandMG.
Cisplatin Neuropathy: a Prospective Study on Chinese Patients
KF Ko, WY Lau, WK Cheng, MC Kwan, LK Yip, KP YiuDepartment of Medicine and Geriatrics, Kwong Wah Hospital, Hong Kong SAR
Background: Cisplatin is a frequently used anti-cancer drug, and with inclusion of this drug incombinationchemotherapy,highremissionratesfordifferenttumourshavebeenachieved.However,itstherapeuticuseislimitedbyadose-dependentandpredominantlysensory,peripheralneuropathy.Methods: Inthisstudy,theincidenceofthiscomplicationwasevaluatedin19Chinesepatientstreatedwithcisplatin120mg/m2every4weeks.Patientswereexcludediftheywereover70yearsold,withahistoryofpreviouschemotherapy,diabetesmellitus,alcoholabuse,brainandleptomeningealinvolvement,AIDSandimpairedliverorrenalfunction.Thepatientswereclinicallyandelectrophysiologicallytestedbeforeandat3,6,9and12monthsaftertheinitiationofchemotherapy.Results: None of the 19 patients examined before treatment showed symptoms or signs orelectrophysiologicalevidenceofneuropathy.Atthecumulativedoseof360mg/m2,12(63%)outofallthepatientsdevelopedsensoryneuropathy.However,onepatientatthecumulativedoseof1080mg/m2hadnoclinicalorelectrophysiologicalevidenceofneuropathywhatsoever,whereasatthecumulativedoseof1440mg/m2,allthesevensurvivorsdevelopedsensoryneuropathyofvaryingseverity.Despitesubstantialinvolvementofsensorynerves,therewasbarelyanychangeinmotornerveconduction.Ototoxicityduetodamageoftheeighthnervewasdetectedineight(42%)patients.Implications/Conclusions: Cisplatin-inducedneuropathyischaracterisedbyasensoryneuropathy.Ithasbeenproposedthatlargemyelinated1afibresarederanged,probablyatthelevelofdorsalrootganglioncells.Surfacerecordingispreferredtothenearneedleelectroderecording,whichhasbeenshowntobemoresensitiveindetectingSAPsofsmallamplitude.
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36 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
A Lady with Autoimmune Lymphocytic Hypophysitis Presenting with Right 3rd, 4th and 6th Palsies
SH LiDepartment of Medicine, North District Hospital, Hong Kong SAR
A52-year-oldladywithgoodpasthealthwasadmittedtohospital inJuly2011becauseofacuteonsetofdiplopiaworstonlookingtotheleftanddroopyrighteyelid.Shedidnothaveheadacheorotherfocalneurologicalsymptom.Examinationrevealedright3rd,4th,and6thpalsies.Pupilsandvisualfield(confrontationtest)wereunremarkable.OtherexaminationsincludingENTwerenormal. HerRFT,LFT,glucose,CBP,CRPandCXRwerenormal.ESRwas60mm/h.CTbrainscanrevealedasellarmass(Fig1).ContrastCTBshowedthickenedpituitarystalk(0.6cm), intensehomogenouslycontrastenhancingmassinvolvingthehypothalamus,infundibulumstalkandpituitarygland.Neithererosionofthesellarfloornorabnormalleptomeningealenhancementwasnoted.CircleofWilliswasnormal(Figs2and3). Immunemarkers,syphilisserology,tumourmarkerswerenegative.Pituitaryhormoneconfirmedpanhypopituitarism(includingcranialdiabeticinsipidusandhyperprolactinemia).CSFshowedslightlyraisedprotein(0.6g/L),normalglucose,mildlyelevatedwbc(8x106/l, lymphocyte90%)butnegativeGram’sstain,AFBsmear,indianink,culture,cytology,andMTBPCRDNA. Theclinicalandradiologicalfindingsandlaboratoryresultswerehighlysuggestiveofautoimmunelymphocytichypophysitis(AIH).Intravenoushydrocortisone100mgq8hwasinitiatedforsecondaryhypoadrenalism,followedby2weeksoforalprednisolone60mg/dayandsubsequenttaperingforAIH.Rapidimprovementincranialnervepalsieswasnotedwithinfewdays.Hydrocortisone,DDAVPandlaterthyroxineweregiven.ContrastMRIbrain/pituitary6daysaftersteroid(Fig4)showedthickenedpituitarystalk(0.4cm),enlargedpituitaryglandwithlossofT1hyperintensesignalofposteriorpituitaryandhomogenouscontrastenhancement.Featurescouldrepresentlymphocytichypophysitis. Thepatientwasdischargedwithalmostcompleteneurologicalrecovery.Follow-upassessmentandMRIwillbeperformed.Herendocrinestatewillbemonitored.
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Fig 1. CT brain, plain Fig 2. Contrast CT brain (coronal)
Fig 3. Contrast CT brain (sagittal)
Fig 4. MRI contrast (coronal)
Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011 37
Long-term Outcome of Stroke Thrombolysis in Hong Kong Chinese Patients
Edward WongDepartment of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR
Background:Emergingdatahavedemonstratedthesafetyandefficacyofstrokethrombolysisinorientalpopulations.Long-termbenefitwasalsoobservedinCaucasianpopulations.However,dataonlong-termoutcomeofChinesestrokepatientswhoreceivedthrombolysisremainlimited.Methods:Clinicalrecordandstrokeregistrydataofconsecutive ischaemicstrokepatientsreceivedintravenousthrombolysiswithin4.5hoursorintra-arterialthrombolysiswithin6hoursbetweenJanuary2007andAugust2010atourcentrewerereviewed.ModifiedRankinScale (mRS)scoresrecordedprospectivelyat3monthswerecomparedtothatat12monthsandatmostrecentclinicfollow-up.Results:Atotalof60patientswereidentified;42receivedintravenousthrombolysisand18underwentintra-arterialthrombolysis.Themeanagewas71.7±11.8yearsandNationalInstituteofHealthStrokeScalescorewas16.5±6.7.Twenty-five(42%)patientsattainedfavourableoutcomeofmRSscore≤2(iefunctional independence)at3months.Therewere11(18%)mortality.Theproportionofpatients(45%)withmRSscore≤2wassustainedat12months.Siximprovedandfiveworsenedbetween3and12months.Atthemostrecentfollow-upatameanof22.5±9.1months,19(32%)patientshaddeceasedbuttheproportion(42%)withmRSscore≤2remainedstatic.Conclusion:The3-monthoutcomeofstrokethrombolysis inourgroupof localpatientsappearedsustainablelongterm.After3months,asmallproportioncontinuestoimproveinfunctionalstatus,whichwasoffsetbypatientswhodeterioratedorsuccumbedduetoadvancedageandcomorbidities.
Do Cerebral Microbleeds Increase Intracranial Haemorrhage Risk in Hong Kong Stroke Patients Receiving Thrombolytic Therapy?
Edward Wong1, Alexander Lau1, Yannie Soo1, Deyond Siu2, Jill Abrigo2, Tom Cheung2, Venus Hui1, Lawrence Wong1
1 Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR2 Department of Imaging and Interventional Radiology, Prince of Wales Hospital, Hong Kong SAR
Background:Cerebralmicrobleeds (MBs)onT2*-weightedmagneticresonance imaging (MRI)areassociatedwithincreasedintracranialhaemorrhage(ICH)risk.Still,strokethrombolysisisregardedassafeforpatientswithMBsasrecentCaucasianstudiesdemonstratedsmallbutinsignificantincreaseinICHrisk.WeaimedtoinvestigateifthrombolysisisequallysafeforlocalChinesepatientswithMBs.Methods:Consecutive ischaemicstrokepatientsreceivedintravenousor intra-arterial thrombolysisbetweenJanuary2007andJune2011withMRIperformedwithin72hourswererecruited.Thepresence,location,andnumberofMBswererecorded.PrimaryoutcomeswereanyICHandsymptomaticICHbyECASS(EuropeanCooperativeAcuteStrokeStudy)definition.Results:Atotalof54patientsintravenousand24intra-arterialthrombolysispatientswereidentified:46ofthemhadMRIperformedwithin72hours;45wereincludedasoneMRIwasaffectedbymotionartefact.MBsweredetectedinnine(20%)patients.Sevenhad1MB,onehad2MBs,andonehad6MBs.NineMBsweresubcorticalandsixwerecortical.One(11%)of9patientswithMBshadasymptomaticICHatdifferentsitesfromMB,versus6(17%)of36patientswithout(P=1.00).NonehadsymptomaticICH.Forreference,among33patientswithnooruninterpretableMRI,10hadICHofwhichfiveweresymptomatic.Conclusion:MBsdidnotappeartoincreaseICHriskfollowingstrokethrombolysisinthisgroupoflocalpatients.However,ourresultsshouldbeinterpretedwithcautionasMRIwasnotuniformlyperformed.UnderestimationofbothprevalenceofMBsandICHriskcouldnotberuledout.
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38 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
Intravenous Thrombolysis Versus Intra-arterial Recanalisation Therapy for Acute Ischaemic Stroke Due to Large Artery Occlusion—Comparison of Outcomes from a Hong Kong Hospital
Edward Wong1, Simon Yu2, Alexander Lau1, Joyce Hui2, Deyond Siu2, Colin Graham3, Cecilia Leung1, Venus Hui1, Lawrence Wong1, Thomas Leung1
1 Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR2 Department of Imaging and Interventional Radiology, Prince of Wales Hospital, Hong Kong SAR3 Department of Accident and Emergency Medicine, Prince of Wales Hospital, Hong Kong SAR
Background:Forischaemicstrokepatientswithlargearteryocclusionandhighclotburden,recanalisationrateislowdespiteintravenoustissueplasminogenactivator(IVTPA).Intra-arterialtherapy(IAT)hasbeenproposedasanalternativebutrandomisedtrialdatacomparingtoIVTPAislacking.HerewecomparedtheoutcomesofourpatientstreatedwitheitherIATorIVTPA.Methods:BetweenJanuary2007andMay2011,consecutivepatientswithlargearteryocclusion(ICA,MCAM1/M2,VA,BA)treatedwithIAT,withonset-to-IAT-at-clottime≤4.5hourswereidentified.FavourableoutcomewasdefinedasmodifiedRankinScale(mRS)score≤2,andmortalityratesat3monthswerecomparedtopatientswithlargearteryocclusiontreatedwithIVTPAatsimilartime-frame.Results:ThirteenpatientstreatedwithIAT≤4.5hourswereidentified.Meanonset-to-IATtimewas209±38minutes(range,150-260minutes).Forcomparison,13receivedIVTPAbetween2.5and4.5hours(mean179±19,range157-230minutes).Therewerenostatisticallysignificantdifferencesinbaselinecharacteristicsofage,NIHSSscoreandCT-ASPECTSbutIVTPAgroupweretreatedearlier(P=0.02).At3months,7(54%)ofIATand5(38%)ofIVTPAgroupattainedfavourableoutcome(P=0.69).Mortalityratewas23%inIATversus8%inIVTPAgroup(P=0.59).Conclusion:NostatisticallysignificantdifferenceswerefoundinfavourableoutcomeandmortalityrateforoursmallgroupofpatientstreatedwithIATorIVTPA.LargerprospectiverandomisedtrialisneededtoseeifIATissuperiortoIVTPAforthispatientsubgroup.Inthemeantime,IATshouldbereservedforpatientswithcontra-indicationtoIVTPA.
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The Efficacy of Deep Brain Stimulation for Advanced Parkinson’s Disease
YF Cheung1, HF Chan1, TL Poon2, PMP Choi2, WS Chan1, FC Cheung2, HM Chan1, P Li11 Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR2 Department of Neurosurgery, Queen Elizabeth Hospital, Hong Kong SAR
Background:Deepbrainstimulation (DBS) isawell-established treatmentmodality foradvancedParkinson’sdisease(PD)patientswhosesymptomsarerefractorytomedical therapyalone.QueenElizabethHospital(QEH)isoneofthelocalpubliccentreswhichprovidesthisservicesinceJuly2000.Methods:WestudiedtheefficacyofDBSinPDpatientsover11yearsbyrecordreview.Results:UptoJune2011,28patientsreceivedDBSinQEH.Subthalamicnucleuswastargetedinallbutonepatients(whoreceivedthalamicventralisintermediusnucleus[Vim]stimulationononesideandSTNstimulationontheother).Eleven(39%)weremale.Themean(±standarddeviation)ageofonsetandsurgerywere43.2±8.9and55.2±7.9,respectively.Threepatientshadalreadydied,tworelatedtodiseaseprogression(pneumonia)andonecommittedsuicidebyinsecticidepoisoning(5yearsaftersurgery).Webelieveoneofthesepatientswhodiedofpneumoniaactuallysufferedfrommultiplesystematrophy,butwhenhereceivedDBStheclassicalsignshadnotyetbeenmanifested(excludedfromtheremaininganalysis). Baselineand1-yearpostoperativeUnifiedParkinson’sDiseaseRatingScale(UPDRS)scoreswereavailablein25and18patientsrespectively,asshowninthefollowingtable.TheimprovementsofUPDRS-IIand-IIIwerestatisticallysignificant.
Significantreductionofanti-Parkinsonianmedicationswasalsoachieved(levodopaequivalentdailydose1090±622mgto587±382mg,P<0.001,pairedsamplesT-test).Tenpatientshadtheirimplantablepulsegenerator (IPG)replacedduetobatteryrun-out.Themedianbattery lifewas7.1years (95%confidenceinterval,5.1-9.0years,Kaplan-Meierestimates).Conclusion:DBS isproventobeefficacious inourcohort. Italleviatessymptomswith feweranti-Parkinsonianmedications.BatterylongevityisanessentialelementwithasignificantimpactontheneedofIPGreplacementandhealtheconomy.
P 7
UPDRS-I UPDRS-II UPDRS-III
Baseline (OFF-med) 4.0 ± 2.7 18.3 ± 6.3 32.7 ± 14.5One-year post-op (OFF-med, ON-stim) 3.8 ± 1.8 12.3 ± 6.3 16.8 ± 9.1P value (paired samples T-test) 0.7 0.001 <0.001
Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011 39
A Case with Atypical Neuroleptic Malignant Syndrome
OC Lau, BH Fung, PW Ng, CH Lo, CK Chan, KY CheungDepartment of Medicine and Geriatrics, United Christian Hospital, Hong Kong SAR
Case reportA22-year-oldmanwithmildmentalretardation,schizophrenia,anxietyneurosisandepilepsy,receivingquetiapine350mgdailyandvalproate400mgBD.Thepatientwasfoundagitatedinworkplace,quarrelledwithworkmatesandquittedthejobfinally.Hethenexperiencedunstablemoodathomeassociatedwithpalpitation,diarrhoeaandreducedoralintakeforrecentfewdays. HeattendedAccidentEmergencyDepartment(AED)for5timeswithin76hoursandjointconsultationwithpsychiatristsatthattimerevealedanxious-lookingpatientwithgeneralisedfinetremors.Duringhis5thAEDattendance,hewasnotedtohaveabodytemperatureof37.5°C.Hewasgivenintramuscularinjectionof5mghaloperidol inviewofunderlyingunstablemoodandsuspectedhallucination.Hewasadmittedtomedicalwardanddevelopedlead-piperigidity,mutism,diaphoresisandsialorrhoea.Furtherdrugcountdiscoveredpatientmissing400mgofquetiapineandpossibilityofdrugoverdosecouldnotbeexcluded.Vitalsignsshowednormalbloodpressurewithsinustachycardiaupto200+bpm.Temperatureraisedupto39°ClaterthesamedayofadmissionwithdecreaseinGCStoE4V1M5.Laboratoryinvestigationshowedmildleukocytosis(WBC16.3x109 /L)andcreatinekinase(CK)levelraisedupto2535IU/L.CTbrainandCSFanalysisdidnotrevealanyabnormality. Allpsychotropicmedicationswerestopped,supportivetreatmentwithbromocriptine, lorazepamandmadopargiven.Cyproheptadinewasempiricallystartedtocoversuspectedserotoninsyndrome.Hisconditiongraduallyimprovedandmusclerigiditysubsided.CKlevelpeakedat8080IU/Londay7andlaternormalised.However,thepatientremainedmuteandtransferredtothepsychiatricwardforfurthermanagement.
DiscussionWith thecommonuseofatypicalneuroleptics, theprevalenceofatypicalneurolepticmalignantsyndrome(whichisamildervariantofNMS)isincreasing.OurcasemaybeacaseofatypicalNMStobegin,withsubsequentdeteriorationtotypicalNMSbytheconcurrentinjectionofhaloperidol.
Headache Associated with Chest Pain and ECG Abnormalities: What Can It Be?
Raymond CK Chan, CH Lo, PW NgDepartment of Medicine and Geriatrics, United Christian Hospital, Hong Kong SAR
Case reportA60-year-oldman,withahistoryofischaemicheartdisease,wasadmittedforconstrictingchestpainandbilateraldullheadache.Thereweremildexertionaldyspnoea,dizzinessandnausea.Physicalexaminationwasunremarkable.ECGshowedQwaveinleadIII,STsegmentdepressionandTwaveinversioninV4-6.Itwastreatedasischaemicheartdiseasewithantiplatelet.Cardiacenzymescamebacknormal.Nextdaymorning,hesuddenlydevelopedgeneralisedtonic-clonicseizure.UrgentCTbrainshowedsubarachnoidhaemorrhage.Cerebralangiogramrevealedanelongatedaneurysmmeasuring2.5mmx5mminthejunctionofleftA1-A2andanteriorcommunicatingartery.Extraventriculardrainageandembolisationofaneurysmweresuccessfulbutheremainedcomatosewithpoorneurologicalrecovery.Severecerebraloedemasecondarytovasospasmdevelopedandhedied5dayslater.
DiscussionThediagnosisofcerebralaneurysmwasmaskedbycardiacsymptomandECGchanges.ItisknownthatthecardiogenicpresentationofSAHspansfromECGabnormalitiestoelevationofcardiacenzymesandregionalwallmotionabnormalities.ThesemanifestationsareduetothesurgeofcatecholaminereleaseaccompanyingSAH.STsegmentabnormalitieswerereportedin15to51%ofSAHandSTdepressionwasmorecommoninpatientswithpooroutcome. Headachewasapredominantsymptominmyocardialischaemiainanumberofcasereports.Inthe2004InternationalClassificationofHeadache,theentity“Cardiaccephalalgia”wasclassifiedinthegroupofsecondaryheadachesattributedtodisorderofhomoeostasis.Itcouldmimicmigraine,tension-typeheadacheorothertypesofheadachesthatcanhardlyclassified. Thiscaseillustratedtwotalesintwosystems.ECGabnormalitiescouldrepresentprimarychangesinmyocardialischaemiaoroccursecondarytoSAH.Headachemaybesignifyingunderlyingintracranialpathologyorsolelythepredominantmanifestationincardiaccephalgia.AttentionshouldbepaidtodifferentiatethecardiacandneurologicalcausesofheadachewithECGchangesandneuroimagingshouldbeconsideredindividually.
P 8
P 9
40 Hong Kong Med J Vol 17 No 6 # Supplement 5 # December 2011
AUTHOR INDEXPageNo.
AJAbrigo 37LWCAu 35
BCBazil 24
CAYYChan 11,35CKChan 39CKMChan 19DTMChan 11HFChan 11,38HMChan 11,38LTChan 11RCKChan 39WSChan 38YCChan 11YHChan 12PPChen 28ACOCheng 19WKCheng 35FCCheung 38GLYCheung 17KYCheung 16,39TCheung 37YFCheung 11,38PMPChoi 38ACPChow 18JMTChu 21YPChu 12
FFSYFan 10,35KFFok 31DFong 31KWFong 11MKFong 12WCFong 11BHFung 39
GCGraham 10,38
HFHui 33JHui 38VHui 10,37,38
IVHLIp 35MIsmail 11
KKFKo 35JKoo 30MCKwan 35FKwok 31
LECLai 22JLam 25
AYLLau 10,35,37,38CLau 11KKLau 12KYLau 11OCLau 39WYLau 35CLeung 10,38TWHLeung 10,35,38PLi 11,38SHLi 36CHLo 39WTLo 11CNPLui 21
MWMak 17BLMan 19KYMok 25,26VCTMok 11,35TMüller 21,22
NNNCNg 35OTWNg 21PWNg 39YWNg 11
PSYYPang 13TLPoon 38WLPoon 31WWSPoon 11
SBSheng 12EShum 10DSiu 10,37,38KPSiu 35YOYSoo 10,35,37
TKToyoda 34THTsoi 29
VDGVossler 23
WKCWang 32SJWang 27AHYWong 11EHCWong 10,35,37,38EWong 11KKWong 14LKSWong 10,35,37,38RWong 11WTWong 12YCWong 31
YESWYeung 15JHMYeung 11
PageNo. PageNo.
LKYip 35KPYiu 35SYu 38LYPYuen 26NYuki 18KKLYung 21
ZDSZee 20XLZhu 11
Acknowledgements
TheOrganisingCommitteewouldliketoextendtheirgratitudetothefollowing
sponsors(inalphabeticalorder)fortheircontinuingsupport:
AllerganHKLtd
BayerHealthcareLtd
BiogenIdec
BoehringerIngelheimHKLtd
Eisai(HK)CoLtd
GlaxoSmithKline
IPSEN(HK)
JanssenPharmaceuticaHongKong
MedtronicInternationalLtd
MerckPharmaceuticalHKLtd
MerckSharp&Dohme(Asia)Ltd
NovartisPharmaceuticals(HK)Ltd
OrientEuropharmaCoLtd
OtsukaPharmaceutical(HK)Ltd
PfizerCorporationHKLtd
SanofiBMSHongKong
ServierHKLtd
Lastbutnotleast,wewouldliketothankallspeakers,chairmen,presentersand
participantsfortheirparticipationandcontribution.