Ho se sebetse hantle ha autonomic prodromal mafung a 'mele a Lewy

letsatsi: E ka ba 2026
E lokiselitsoe ke Litho tsa SIC: Sephira Ryman, PhD, le Michele Matarazzo, MD
bangodi: David S. Goldstein, MD, PhD, Abhimanyu Mahajan MD, MHS; Alison Yarnall, PhD, MBBS 
Bahlophisi: Lorraine Kalia, MD, PhD; Per Svenningsson, MD, PhD

Selelekela

Ho se sebetse hantle ha tsamaiso ea 'mele ea ho iketsahalla ha lesea ho hlahile e le sebaka sa bohlokoa sa lipatlisiso ho utloisiseng mafu a 'mele oa Lewy, ho kenyeletsoa le lefu la Parkinson (PD) le Dementia le 'mele ea Lewy (DLB). Bopaki bo ntseng bo eketseha bo bontša hore mathata a methapo ea pelo, mala, moroto, tsamaiso ea thermoregulatory le a mang a ikemetseng a ka 'na a etella pele matšoao a khale a ho tsamaea kapa a ho nahana ka lilemo.  

Puisano ena e ikemiseditse ho buisana ka bopaki bo tšehetsang ho se sebetse hantle ha boits'oaro ba 'mele mafung a prodromal Lewy, ao libaka tsa 'mele tse ikemetseng li ka bang le tlhahisoleseling e ngata bakeng sa ho lemoha kapele, lisebelisoa tse hlahang tsa tlhahlobo, le temohisiso ea liphuputso tsena le bohlokoa ba tsona tlhokomelong ea bongaka.   

Sengolwa sena sa blog se hlahisitsoe ka tshebedisano mmoho le Michelle Matarrazo le MDS Podcast. 

Mamela karolo ea podcast:

Mamela hona joale

1. Ke bopaki bofe ba kliniki kapa ba biomarker bo tšehetsang boteng ba ho se sebetse hantle ha boits'oaro ba 'mele karolong ea prodromal ea mafu a 'mele a Lewy?  

Ngaka David Goldstein

Bopaki bo matla ka ho fetisisa ba ho se tloaelehe ho itseng ha autonomic mafung a mmele a Lewy bo tsoa ho cardiac sympathetic neuroimaging. Tlaleho ea rona ea pele ka 1997 ho New England Journal of Medicine e hlalositse ka lekhetlo la pele hore ho bakuli ba nang le mafu a mmele a Lewy, lefu la Parkinson le pure autonomic failure, ba bontša tahlehelo ea methapo ea kutlo ea myocardial sympathetic re sebelisa [18F] fluordopamine PET scanning. Ha rea ​​ka ra bontša liphapang ho non-Lewy body synucleinopathy, Shy-Drager syndrome, e ileng ea bitsoa multiple system atrophy. 

Ho theosa le dilemo tse mashome a mararo tse fetileng re tiisitse diphihlello tsena kamora lefu ka ho hlahloba dikahare tsa norepinephrine pelong. Hona jwale ha ho pelaelo hore ho na le kgaello e tebileng ya noradrenergic ya pelo mafung a mmele a Lewy mme ka kakaretso ha ho le e nngwe ho atrophy ya ditsamaiso tse ngata.  

Ke neng nakong ea mafu ana moo ho se tloaelehe hona ho iketsahallang ho bonahalang? Bonyane ho seo hona joale se bitsoang mofuta oa pele oa 'mele oa synucleinopathies e bohareng, leqeba la kutloelo-bohloko ea pelo le etella pele ho qaleha ha Parkinsonism kapa ho se sebetse hantle ha kelello joalo ka ha ho le joalo ka lefu la 'dementia' le nang le 'mele ea Lewy.

Ngaka Abhimanyu Mahajan

E 'ngoe ea lipampiri tsa pele tse ntle ka ho fetisisa mabapi le taba ena e phatlalalitsoe ka 2013 ke Moprofesa Ron Postuma, moo a hlalositseng litšobotsi tsa autonomic sehlopheng sa bakuli ba 91. Ba hlokometse bonyane letšoao le le leng ka subdomain e ikemetseng, e neng e kenyelletsa matšoao a orthostatic, ho se sebetse hantle ha moroto, ho pipitleloa, le ho se sebetse hantle ha botona kapa botšehali mohatong oa prodromal oa lefu lena.  

Haufinyane re sebelisitse database ea Parkinson's Progression Markers Initiative (PPMI) ho lekola hore na moroalo oa pele oa autonomic o bolela esale pele ho senyeha ha kelello ho PD ea prodromal. Re sebelisitse Scales for Outcomes in Parkinson's Disease Autonomic Dysfunction (SCOPA-AUT), e leng sekala se netefalitsoeng ke MDS. Haeba u nka karabo e ntle ho e 'ngoe ea lipotso tseo karolong e 'ngoe le e 'ngoe ea subdomain, hoa makatsa hore na bakuli ba bakae ba prodrome ba na le bonyane letšoao le le leng la autonomic. 

Ngaka Alison Yarnall

Ho DLB ea prodromal, e leng ho fokola ho fokolang ha kelello ka 'mele ea Lewy, re na le lihlopha tse tebileng tsa phenotype mona Newcastle tseo re li latetseng ka lilemo tse 'maloa' me ra li bapisa le ho fokola ho fokolang ha kelello ka Alzheimer's le ka taolo. Ka sebele, ho tsoa phihlelong ea rona, re fumane hore matšoao a ikemetseng a ne a tlalehoa hangata, 'me seo se ne se tloaelehile haholo ha se bapisoa le botsofali bo tloaelehileng. Leha ho le joalo, e ne e se ntho e tloaelehileng haholo ha e bapisoa le ba nang le MCI ba nang le mofuta oa Alzheimer's pathology.  

1.1. Na libaka tse ikhethileng tse ikhethileng (mohlala, pelo le methapo ea mali khahlanong le mala) hangata li sa tloaeleha ho lihlopha tsa prodromal?  

Ngaka Abhimanyu Mahajan

Ho na le lebaka la hore ho se sebetse hantle ha pelo le methapo ea mali ho na le tšusumetso e matla phetohong ea phenoconversion le liphellong tsa kelello. Re bontšitse hore ho se sebetse hantle ha pele ho its'ebetso ea 'mele ho thehiloeng ho SCOPA-AUT ho ne ho amahanngoa haholo le kotsi e eketsehileng ea ho se sebetse hantle ha kelello kapa dementia (P < 0.001). Moroalo oa matšoao a its'ireletso ea pelo le methapo ea mali, haholo-holo, e ne e le ponelopele e matla e ikemetseng (HR = 5.21, P = 0.01). 

Ho se sebetse hantle ha methapo ea mali ho entse hore ho be le li-biomarker tse matla tse hlahisitsoeng. Leha ho le joalo, ha re ntse re tseba haholoanyane, re tseba hanyane haholo hore na re tseba hanyane hakae ka ho se sebetse hantle ha methapo ea mali. Haeba li-biomarker tse betere li hlahisoa likarolong tse ling tse nyane, tsena li ka ba le tšusumetso e kholo ka ho lekana, haeba e se eona.  

1.2. Matšoao a ikemetseng a prodromal a bapisoa joang ka kutloisiso le ho totobala le matšoao a mang a prodromal?

Ngaka Alison Yarnall

Re fumane hore matšoao a mala le a secretory psychomotor a ne a atisa ho tlalehoa, empa matšoao a pelo le methapo a ne a le matla haholo ho lihlopha tsa rona tsa prodromal DLB. Bongata ba matšoao ana a na le kutlo e phahameng, kahoo a atisa ho ba teng. Re a bona maemong a fetang halofo a prodromal DLB, haholo-holo ho pipitleloa kapa hypotension ea orthostatic. Matšoao ana a na le ho hlaka ho tlase haholo ha a bapisoa le matšoao a mang a mantlha ao re a bonang, joalo ka boteng ba REM sleep behavior disorder kapa dopamine transporter imaging e sa tloaelehang. 

Ke sebaka se ntseng se fetoha 'me re ntse re lemoha ho se sebetse hantle ha boits'ireletso ba 'mele haholoanyane. Ka lehlakoreng le leng, matšoao ana a mangata a boetse a tlalehoa hangata ho batho ba baholo.

2. Ke mekhoa efe e hlahang ea ho lekola ts'ebetso ea boikemelo e nang le tšepiso e kholo ea ho lemoha lefu la prodromal?   

Ngaka David Goldstein

Hypotension ea orthostatic ha e fumanoe hantle. Lingaka tsa methapo ea kutlo hangata ha li nahane ka hona ntle le haeba mokuli a e-na le letšoao. U tla nyenyefatsa makhetlo a hypotension ea orthostatic haeba u itšetlehile ka matšoao.  

Ho na le di-biomarker tsa fisioloji, tsa methapo, tsa ditshwantsho tsa methapo, le tsa micro-neuroimaging tse kopanang setshwantshong sa Venn. Ha ho tluoa tabeng ya fisioloji, di-indices tsa baroreflex le tshebetso ya methapo ya kutlo e ka ba molemo. Ha ho tluoa tabeng ya dikhemikhale tsa methapo, maemo a CSF a di-catecholamine le di-metabolite tsa tsona a ka ba molemo. Ha ho tluoa tabeng ya ditshwantsho tsa methapo, re se re buile ka ho hlahloba pelo ya PET ho PD le DLB ya mmele pele. Lefatsheng la nnete, ho hlahloba MIBG SPECT ho ka ba molemo. Ha ho tluoa tabeng ya ho hlahloba methapo ya kutlo e ka ba molemo. Ha ho tluoa tabeng ya ho hlahloba methapo ya kutlo e ka ba molemo, di-biopsies tsa letlalo di ka ba molemo, di batla ho bewa ha alpha-synuclein methapong ya kutlo e fanang ka methapo ya madi, di-gland tsa mofufutso, le mesifa ya arrector pili. Ntle le khemikhale ya kutlo mabapi le di-catecholamine, ho na le ho mela ha di-synuclein tsa CSF, e neng e le ponelopele thutong ya rona ya bokamoso ba nako e telele. 

Nakong e tlang, ke tšepa hore ho tla ba le phetoho ho tloha ho hlahlobisiso ea bongaka feela ho ea ho mokhoa oa algorithmic o kenyelletsang li-biomarker. Qala ka lintho tse potlakileng, tse theko e tlase, tse sireletsehileng, empa tse nang le kutlo e lekaneng - ho tloha ntlheng eo ea pono, tlhahlobo ea phapang ea sekhahla sa pelo haholo-holo sebakeng sa maqhubu. Kamora moo, fetela ho matšoao a synuclein a lateloang ke fluorodopa PET scanning ea boko. Haeba ho ka etsoa, ​​fluorodopamine PET scanning ea pelo.  

Ngaka Abhimanyu Mahajan

Ho ba le li-biomarker tse ikhethang haholo ho bohlokoa hore re utloisise pathophysiology. Hase feela pathophysiology, empa le fisioloji ea hore na tsena tsohle li sebetsa joang. Ka nako e ts'oanang, ho na le molemo o mongata oa ho se nyenyefatse melemo ea seo re ka se etsang pela bethe.  

Khatello ea mali ea Orthostatic ha e sebelisoe hantle. Re entse phuputso Univesithing ea Cincinnati 'me ra hlahloba litekanyo tsa hypotension ea orthostatic pela bethe. Hoo e ka bang 30% ea bakuli ba ne ba sa tsebe hore khatello ea mali ea bona e ne e le orthostatic. Habohlokoa le ho feta, leha ba ne ba se na matšoao, kotsi ea mesebetsi e mebe ea bophelo ba letsatsi le letsatsi le ho oa e ne e ntse e le holimo, e totobatsang hore leha mokuli a sa lemohe hypotension ea orthostatic, ha ho bolele hore ha e na tšusumetso.  

Ho sa tsotellehe kutloelo-bohloko e fokolang ea matšoao, ho bohlokoa haholo ho a tšoara pela bethe. Boitsebiso bo bongata boo re nang le bona mabapi le tšusumetso ea moroalo oa matšoao a orthostatic le tšusumetso ea ona libakeng tse ling ho PD bo tsoa lithutong tsa ho shebella le lihlopha tse lateloang kliniking, tse kenyeletsang mehato e kang SCOPA-AUT le tse ling. Ke habohlokoa ho tšoara nakong eohle ea lefu lena. Bokhoni ba ho etsa litekanyo tsena le litlhahlobo tsena pela bethe bo re fa bokhoni ba ho hapa tlhahisoleseling ho tsoa boholo ba lisampole tse kholo tse re thusang ho hlalosa tse ling tsa ho se tšoane ha lefu leo ​​​​re le bonang. 

Mekhoa ea biomarker le ea bongaka ea ho lekola ho se sebetse hantle ha autonomic e tlameha ho sebetsa ka nako e le 'ngoe. Ehlile, ke ea mahala. 

2.1. U bona tlhokomelo e tsoelang pele ea hole e ntlafatsa tlhahlobo ea mafu le kutloisiso ea rona ea 'nete ea bakuli ba kantle ho tleliniki joang?

Ngaka Alison Yarnall

Tlhokomelo e tsoelang pele ke tsela eo lefatše le tsamaeang ka eona. Mona UK re na le moralo oa lilemo tse 10 bakeng sa NHS ea rona. E 'ngoe ea litšiea tse tharo ke ho tloha sepetlele ho ea sechabeng, ho tloha ho bokuli ho ea thibelong, ho ea ho ho laola tlhokomelo lapeng. Sena se tla thusa ho lekanya ho se sebetse hantle ha boits'ireletso, hammoho le mehato e meng e mengata, joalo ka boroko, mokhathala, ho tsamaea, ho tsamaea le ho lemoha. Ho lekanya sena tikolohong ea motho ka nako ea matsatsi a supileng, kapa e tšoanang, ho bolela hore ha rea ​​​​lokela ho itšetleha ka setšoantšo se le seng se ke keng sa hapa liphetoho tse teng tse leng karolo ea PD le DLB.  

Ho ka ’na ha fokotsa moroalo oa nako ea lingaka. Haeba re na le liphello tsa bakuli ka nako ea sebele, re ka ’na ra khona ho etsa liphetoho re le hole ho thibela batho ho tla kliniking. E lumella ho kenyelletsoa hape. Bakuli ba hōlileng, ba fokolang, batho ba mahaeng ba tla ba le tlhokomelo e tšoanang le ea ba lulang haufi le litsi tsa univesithi mabapi le menyetla ea bongaka le ea lipatlisiso. 

Ho nka mokhoa oa algorithm o tšoanang le oo David a buileng ka oona e ka ba mokhoa o motle ka ho fetisisa. Ho hapa litekanyo tse ngata le lintlha ho ka ntlafatsoa ho khetholla ba hatelang pele ka potlako, butle-butle, le ba hlokang thuso. 

Ngaka David Goldstein

Nka eketsa mehato ea ho lekola khatello ea mali khafetsa. Ho bohlokoa haholo ho fumana hore na khatello ea mali e phahameng hakae motšehare. Hangata e mpefala hoseng, 'me haeba e mpefala hoseng, u ke ke ua phekola motho ka vasoconstrictor bosiu le motšehare.  

3. Ke litlamorao life tsa kliniki tseo temohisiso ena e nang le tsona bakeng sa ho arola likotsi le ho beha leihlo batho ba nang le bothata ba ho se sebetse hantle ha prodromal autonomic?  

Ngaka David Goldstein

Ke tla bua ka thuto ea kotsi ea PD hobane ke e 'ngoe ea lithuto tse 'maloa tse tsoelang pele tsa batho ba nang le mabaka a mangata a kotsi ho fumana boleng ba ho bolela esale pele ba mefuta e fapaneng ea li-biomarker. Ponelopele, e thehiloeng feela linthong tse kotsi, nalane ea lelapa, boitšoaro ba ho etsa litoro, ho se sebetse hantle ha monko, le ho se mamelle ha orthostatic li matla haholo. Ha li kopantsoe li eketsa haholo liphello tsa ho bolela esale pele le tsa ho bolela esale pele mabapi le phenoconversion nakong e tlang. Ha li-biomarker tsa laboratori tse nang le sepheo sa catecholamine ea khaello ea alpha-synucleinopathy li eketsoa, ​​​​ha e le hantle ha e sa le taba ea kotsi. U na le lefu lena. Ke taba ea nako pele matšoao a kliniki a hlaha. Li-biomarker tseo li tla fetola kotsi e lekanyelitsoeng ho ea ho lekholo la liphesente. Bokamoso bo ka ho eketsa li-biomarker linthong tse kotsi tseo re seng re buile ka tsona.  

4. Ha re sheba pele, litlamorao tse ka bang teng tsa kalafo ke life?  

Ngaka Alison Yarnall

Mohlomong nakong e tlang, mokuli a ka tla tleliniking, o tla tsebahatsa fisioloji ea autonomic le matšoao a ka sebelisoang ho hlalosa mekhoa ea bona ea phekolo le mekhoa ea bona ea phekolo. Litšobotsi tsa autonomic prodromal li ka re bolella ka kotsi le karohano ea likotsi. Seo se ka fana ka tšehetso ho bao u ba behileng tekong ea bongaka. 

Teko ea kliniki ea ho qetela e tla ba ntho e thibelang motho ho fetoha ho tloha lefung la prodromal ho ea ho DLB kapa PD e hlakileng. Litšobotsi tsa kliniki le tsa biomarker tsa lefu la autonomic li ka re thusa ho etsa qeto ea hore na ke mang ea kenang tekong efe ea kliniki. 

Ngaka Abhimanyu Mahajan

Ho ntlafatsa liteko tsa kliniki ke tsela e nepahetseng ka ho feletseng. Joale kaha re tseba hore ho se sebetse hantle ha autonomic pele ho nako ho amahanngoa le nako e potlakileng ea phenoconversion, ho kula ho hoholo, ho phela hanyane, mohlomong le kotsi e kholo ea kelello, ho bohlokoa ho arola sampole litekong tsa kliniki.

5. Lintho tsa bohlokoa tsa lipatlisiso tsa hona joale ke life sebakeng sena?

Ngaka David Goldstein

Ho hlwaya di-biomarker tsa lefu la pele ho tleliniki. Esita le lefung la pele ho tleliniki ho se ho ntse ho na le tshenyo e kgolo. Tshepo ya bokamoso ke ho hlwaya tshebetso ya lefu pele motho a ba le matshwao ho hang. Sepheo ha se ho lelefatsa nako ya lefu le nang le matshwao, ke se fapaneng feela. Sepheo ke ho diehisa ho qaleha ha lefu le nang le matshwao. Haeba o ne o ka lelefatsa nako ya bophelo bo botle, eo e ne e tla ba sepheo sa setjhaba.  

Ngaka Alison Yarnall

Taolo ea matšoao ana a boima ho a phekola a ikemetseng e bohlokoa. Ho na le khaello e itseng motheong oa bopaki ba hona joale, 'me hangata e ama boleng ba bophelo haholo. Seo e tla ba sona seo ke tla se etsa lipatlisisong tsa ka tse ka sehloohong.

Ngaka Abhimanyu Mahajan

Ho fumana litsela tsa ho tšoara moroalo oa autonomic bakeng sa mokuli e mong le e mong ea nang le synucleinopathy ea tlang kliniking, ebang ke mokuli ea hlahetsoeng ke lefu la pele ho nako, PD ea pele ho nako, kapa DLB ea morao. Hafeela u ka khona ho e tšoara ka nepo le ho phekola matšoao ao, eseng feela bakeng sa phello ea matšoao ao, empa hape, 'me ena ke pie setšoantšong se leholimong, ho thibela matšoao a amanang le ona nakong e tlang. Seo e tla ba ntho ea pele ho 'na.  

Hape ha re na dikgetho tse lekaneng ts'ebetsong ea rona ea ho hlasela bothata ba kelello. Ho se sebetse hantle ha boits'oaro, ho kenyeletsoa le ho se sebetse hantle ha pelo le methapo ea mali, ho ka ba molemo ho ho shebana le ho ntlafatsa bothata ba kelello. Re hloka ho tseba mekhoa e ntlafatsang kutloisiso.  

References

1. Goldstein DS, Holmes C, Cannon RO, Eisenhofer G, Kopin IJ. Bolwetse ba pelo bo amang maikutlo ho dysautonomias. N Engl J Med 1997;336(10):696–702. doi:10.1056/NEJM199703063361004 

2. Goldstein DS, Holmes C, Lopez GJ, Wu T, Sharabi Y. Ho se sebetse hantle ha pelo ho bolela esale pele lefu la Parkinson ho batho ba kotsing. Parkinsonism Relat Disord 2018;52:90–93. doi:10.1016/j.parkreldis.2017.10.003 

3. Goldstein DS. Li-biomarker tsa pele ho kliniki tsa catecholaminergic tsa mafu a 'mele a bohareng ba Lewy. J Clin Neurol 2026;22(1):6. doi:10.3988/jcn.2026.22.1.6 

4. Hamilton CA, Frith J, Donaghy PC, Barker SA, Durcan R, Lawley S, Barnett N, Firbank M, Roberts G, Taylor JP, Allan LM, O'Brien JT, Yarnall AJ, Thomas AJ. Tlhahlobo ea matšoao a ikemetseng e ka thusa ho lemoha kapele mathata a fokolang a kelello a amanang le 'mele ea Lewy. Int J Geriatr Psychiatry 2022;37(4). doi:10.1002/gps.5697 

5. Hamilton CA, Frith J, Donaghy PC, Barker SA, Durcan R, Lawley S, Barnett N, Firbank M, Roberts G, Taylor JP, Allan LM, O'Brien JT, Yarnall AJ, Thomas AJ. Khatello ea mali le karabelo ea sekhahla sa pelo ho phephetso ea orthostatic le mokhoa oa Valsalva oa ho sitisoa ke tsebo le 'mele ea Lewy. Int J Geriatr Psychiatry 2022;37(5). doi:10.1002/gps.5703 

6. Martinez-Nunez AE, Mills KA, Seemiller J, Morrow CB, Pontone GM, Mahajan A. Moroalo oa pele oa boikemelo lefung la Parkinson la prodromal o bolela esale pele ho fokola ha kelello. Mov Disord 2026. doi:10.1002/mds.29972 (epub pele ho khatiso) 

7. Mahajan A, Morrow CB, Seemiller J, Mills KA, Pontone GM. Phello ea dysautonomia ho feto-fetoha ha methapo ea kutlo, boitšoaro le tsebo ho lefu la Parkinson. Mov Disord 2025;40(1):157–162. doi:10.1002/mds.29614 

8. Mahajan A, Dwivedi AK, Galvin JE, Maixner SM, Paulson HL, Manning CA, Fields JA, Boeve BF, Mills KA, Morrow C, Pontone GM, Armstrong MJ. Ho feto-fetoha ha kelello, moroalo oa methapo ea kutlo, le boleng ba bophelo ho dementia e tsoetseng pele ka tekanyo e itekanetseng le 'mele ea Lewy: karolo ea dysautonomia. Neurology 2026;106(9):e214934. doi:10.1212/WNL.0000000000214934 

9. Merola A, Romagnolo A, Rosso M, Lopez-Castellanos JR, Wissel BD, Larkin S, Bernardini A, Zibetti M, Maule S, Lopiano L, Espay AJ. Ho fokotseha ha khatello ea mali ho bakoang ke lefu la Parkinson: na hoa tsotelleha hore na ha ho na matšoao? Parkinsonism Relat Disord 2016;33:65–71. doi:10.1016/j.parkreldis.2016.09.013 

10. Patino J, Duque K, Abanto J, Bloemer A, Deraz H, Espay AJ, Mahajan A. Liketsahalo tse nang le khatello e phahameng ea mali li etella pele ho feto-fetoha ha kelello ho lefu la Parkinson dementia. Mov Disord Clin Pract 2026. doi:10.1002/mdc3.70590 (epub pele ho khatiso) 

11. Postuma RB, Gagnon JF, Pelletier A, Montplaisir J. Matšoao le matšoao a autonomic a Prodromal lefung la Parkinson le dementia ka 'mele ea Lewy. Mov Disord 2013;28(5):597–604. doi:10.1002/mds.25473