Kusagadzikana kweprodromal autonomic muzvirwere zvemuviri weLewy

 Nhasi, ndinofara kubatana nenyanzvi nhatu dzakakurumbira, David Goldstein wekuNIH, ane basa guru mukutsanangura basa rekutadza kwemuviri uye kushomeka kwecatecholamine muzvirwere zvesynucleinopathies, kusanganisira zvidzidzo zvakakosha pakukundikana kwemuviri sechirwere cheprodromal.

David, tinokutendai nekubatana nesu [00:01:00].

 Abhimanyu Mahajan ane basa rake raachangobva kuita rakatarisana nekushanda zvisina kunaka kwemuviri sechiratidzo chekutanga chezvirwere zvinoderedza mashandiro etsinga, kusanganisira chidzidzo chake chaachangobva kuita chekuongorora maitiro emuviri muprodromal synucleinopathies. Abhi, tinokutendai nekuva nesu nhasi.

Dr. Abhimanyu Mahajan: Ndatenda Michele, uye ndatenda nekundigamuchira.

Dr. Michele Matarazzo: Uye Alison Yarnall, purofesa wezvekurapa kwevanhu vakwegura anozivikanwa nebasa rake pakuongorora zviratidzo zveLewy body diseases uye zvisiri zvekufamba kwemuviri, kusanganisira zvidzidzo zvenguva refu pa prodromal dementia neLewy bodies uye early non-motor phenotyping. Ndatenda, Alison, nekuve neni nhasi.

Dr. Alison Yarnall: Ndatenda nekukoka.

Dr. Michele Matarazzo: Saka, David, regai nditange newe. Basa rako rakanyatsogadzira maonero edu nezvekusashanda zvakanaka kwemuviri sechiratidzo chekutanga chesynucleinopathy. Ndeupi humbowo hwekiriniki kana hwebiomarker hunotsigira kuvapo kwekusashanda zvakanaka kwemuviri muchikamu cheprodromal chezvirwere zvemuviri zveLewy?

Dr. David Goldstein: Ndinofunga kuti humbowo hwakasimba hunobva mukuongorora kwemwoyo kunobatsira vanhu kunzwa marwadzo. [00:02:00] Hazvirevi kuti I-123 MIBG ndiyo inoshandiswa pasi rese. Uye tinogona kutaura nezvazvo gare gare, kana zvichidikanwa. Asi ne fluordopamine, [18F]fluordopamine PET scanning, yandakagadzira paNIH kare kare, uye yandakashandisa kwemakore anopfuura makumi matatu.

Mushumo wekutanga waive muna 1997 muNew England Journal of Medicine uye mumushumo iwoyo takatsanangura kekutanga musiyano uripo pakati pezvirwere zvemuviri zveLewy, kukundikana kwemuviri muchirwere cheParkinson. Uye chirwere cheNon Lewy body synucleinopathy, Shy-Drager syndrome, iyo yakazonzi multiple system atrophy.

Mumakore makumi matatu apfuura takasimbisa kuongororwa kwemuviri mushure mekufa nekutarisa norepinephrine mumoyo. Uye hapana mubvunzo kuti pane kushomeka kwakakura kwechirwere chemwoyo chinonzi noradrenergic [00:03:00] muzvirwere zvemuviri zveLewy. Uye kazhinji hapana kana chimwe chazvo mu multiple system atrophy.

Saka iyi biomarker haina kungosiyanisa mamiriro ezvinhu chete, asiwo yakasimbiswa ne postmortem neurochemistry. Ehe, mubvunzo unomuka, izvi zvinoitika riini? Uye izvozvo zvakatora nguva yakareba, asi ikozvino zvave pachena kuti zvirinani mune, chinonzi muviri fomu yekutanga ye central synucleinopathies, iyo zvakare, tinogona kupinda mairi gare gare.

Asi zvirinani muchimiro chekutanga chemuviri, hapana mubvunzo kuti chirwere chemwoyo chinotangira kutanga kweParkinsonism kana kusagadzikana kwepfungwa sekunge kune dementia ine Lewy bodies. Zvakabuda mu fluorodopamine cardiac zvakasimbiswawo ne cardiac catheterization zvichiratidza kuti kune kudzikira kukuru kwehuwandu hwe norepinephrine mu venous range yemoyo muzvirwere zveLewy body kwete mu multiple [00:04:00] system atrophy.

Saka ndinofunga kuti chirwere ichi chinosarudza mwoyo muzvirwere zvemuviri zveLewy. Uye pakupedzisira pane nyaya yekuti chii nezve synucleinopathy kune dzimwe nzvimbo, uye ndine chokwadi chekuti tichataura nezve ganda biopsies uye synuclein seeding activity uye gut and vagal afferent traffic nezvimwewo uye kuti izvi zvine hukama sei zvichiri chakavanzika.

Uye ndinofunga kuti izvozvo zvakakosha. Kana uine biopsy yeganda inoratidza kuiswa kwealpha-synuclein uye tsinga dzinonzwa tsitsi, uye uine synucleinopathy yakaonekwa paongororo yakaitwa mudumbu, uye unoita iyi cardiac sympathetic imaging. Zvinobatana sei? Uye zvakanyanya, hapana anoziva.

Dr. Michele Matarazzo: Ehe. Wanyatsogadzira pano neruzivo rwakawanda nezvezviratidzo zvakasiyana-siyana uye nzira dzakasiyana dzekuyera izvi. Uye Abhi, pamwe regai ndikuudzei [00:05:00] pano. Pane here zvimwe zvikamu zve autonomic zvakaita sekusashanda zvakanaka kwemwoyo kana gastrointestinal, kana zvimwe zviratidzo zveweti, zvinowanzova zvisina kujairika mu prodromal cohorts?

Dr. Abhimanyu Mahajan: Chekutanga, ndaigona kungoteerera Dr. Goldstein vachitaura nezveizvi kwemaawa mashoma, uye ndiyo inguva yakanakisisa yati yamboshandiswa. Zvandakasangana nazvo zvechokwadi kuti hatina mukana wekuwana zvinhu zvinoshamisa zvakagadzirwa naye kuNIH uye chikamu chikuru chezvandave ndichiedza kuita ndechekutarisa mapoka ekurapa uye kutarisa zviyero zvechikero kuti ndione kuti zvingabatsira sei varwere vedu.

Seti yedata yatakashandisa yaive PPMI, iyo Parkinson's Progressions Markers Initiative, iyo sezvatinoziva iri sosi yakawanda yedata pamusoro pevarwere, pamusoro pevanhu vane chirwere cheParkinson's prodromal. Ehe, kwave kune mamwe maseti edata kare zvakare, mamwe mapoka munguva yakapfuura.

Ndinofunga ndinofanira kutanga nekutaura kuti rimwe remapepa akanakisa panyaya iyi pakutanga raive ra2013 rakanyorwa naProfessor Ron Postuma, kwavakatsanangura maitiro e autonomic, zviratidzo zve autonomic [00:06:00], uye zviyero zvekiriniki padivi pemubhedha, zvakaita se orthostatic hypotension muboka revarwere vangangoita vapfumbamwe, uye boka rakanaka re control.

Uye akataura kuti paiva nechiratidzo chimwe chete pachikamu chimwe nechimwe chemuviri. Saka kana uchitaura nezvemwoyo, gastrointestinal, genital, weti, bonde, nezvimwewo, akatsanangura chiratidzo chimwe chete pachikamu chimwe chete muhuwandu hwevarwere ava vane chirwere cheParkinson's uye muPPMI zvakare. Zvinova zvakaoma nekuti unoda kubvisa hanyanisi zvakadii, handiti?

Saka kana uchida kuti ive inonzwisisika zvakanyanya uye uchida kufunga nezvemubvunzo mumwe chete, saka chiyero chakashandiswa chaive SCOPA-AUT, inova chiyero chakabvumidzwa neMDS, uye chave chichishandiswa kwemakore akati wandei. Uye chikamu chimwe nechimwe, chikamu chimwe nechimwe chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega chega, saka zvinoshamisa kuti vangani vevarwere ava [00:07:00] vanonzi vane chirwere cheprodromal muchirwere chavo uye prodromal vanotsanangurwa nekutanga kwezviratidzo zvemota, hongu. Vanenge vese vachave nemubvunzo mumwe chete wavanopindura kuti hungu.

Sezvakataurwa naDr. Goldstein, mhedzisiro huru yatakanga tichiongorora, iyo iri kushaya simba kwepfungwa, mutoro wezviratidzo zvemwoyo neropa, ndiyo yatakaona kuti ndiyo yakanyanya kukosha, ine huwandu hwengozi hwakanyanya hwe5.21. Asi hongu, paivawo nevamwe.

Dr. Michele Matarazzo: Saka unofunga kuti zviratidzo zvemwoyo ndizvo zvine simba pari zvino kana kuti uri kufunga kuti tiri kurerutsa zvimwe zvinhu zvakaita sematumbu kana kuti pane kusashanda zvakanaka kwemuviri, pane chimwe chinhu chatisingataure nezvacho.

Dr. Abhimanyu Mahajan: Ndinofunga kuti pane zvakanakira izvozvo. Ndinofunga kuti kusashanda zvakanaka kwemoyo neropa kwakakonzera kuti ma biomarker akasimba agadziriswe pasina mubvunzo. Uye ndinofunga kuti kana tichiziva zvakawanda, ndipo patinoziva zvishoma. Saka, handingashamisike kana ma biomarker ari nani akagadziriswa mune mamwe ma subdomains toawana.

Zvinozivikanwawo [00:08:00], chidzidzo chandiri kufunga nezvacho chidzidzo chePD risk kubva kuNIH, asi kwave nemamwe mapoka futi. Kunyangwe ukarega kutaura nezve prodromal Parkinson's disease totarisa bepa razvino rakaburitswa kubva kuUCL London pamusoro pekukundikana kwe autonomic. Mapoka ese aya anotaura nyaya yakafanana.

Saka kana ukanyanya kutarisa pamutoro wemwoyo neropa, hongu, uchawana hukama nepfungwa. Uchawana hukama nekushanduka kwe pheno, kunyange kurarama, asi kuvimbiwa, nhengo dzepabonde, kushandiswa kwe catheter yeweti, nezvimwewo, zvave zvichibatanidzwa nekushanduka kwe pheno kuita MSA, semuenzaniso, panzvimbo pePD DLB, handiti?

Ndinofunga kuti kana tikanyatsoongorora, tichawana hukama hwakasimba kwete nekuchinja kwe pheno chete, asiwo kuchinja kwe pheno kuenda kurudzi rwechirwere.

Dr. Michele Matarazzo: Uye Alison, ndinoda kuti uuye nemaonero ako pano kunyanya tichifunga nezvebasa rako pa prodromal dementia ine Lewy bodies uye cognitive first phenotypes. Zviratidzo zve autonomic zvinoenzaniswa sei mu sensitivity uye [00:09:00] specificity nezvimwe zviratidzo zve prodromal, zvakaita se, REM sleep behavior disorder, cognitive fluctuation pa neuropsychiatric symptoms?

Dr. Alison Yarnall: Ndiri kufunga kana ndingogona kudzokera shure ndotanga ndafungisisa zvishoma zvaitaurwa naAbhi totaura nezvechiitiko chedu mu prodromal dementia neLewy bodies. Saka tichitarisa mild cognitive impairment neLewy bodies, uko tine deep phenotype cohorts pano muNewcastle yatakatevera kwemakore akati wandei uye takaienzanisa ne mild cognitive impairment neAlzheimer's uye ne controls.

Zvechokwadi kubva pane zvakaitika kwatiri, takaona kuti zviratidzo zvemuviri zvaiwanzotaurwa, uye izvozvo zvaiwanzoonekwa zvakanyanya kana tichienzanisa nekukwegura kwakajairika, asi kutaura chokwadi, zvaisaonekwa zvakanyanya kana tichienzanisa nevaya vane MCI vane chirwere cheAlzheimer's type pathology. Uye zvakare, sezvakataurwa naAbhi, tiri kutengesa nyaya imwe chete.

Takawana kuti zviratidzo zvemudumbu uye zvepfungwa zvinobuda mudumbu zvaiwanzotaurwa, asi zviratidzo zvemwoyo zvakataurwa kuti zvakanyanya kuipa.

Saka kuti tiende pane zvamakandibvunza zvakananga ndezvekuti tingaenzanisa sei kusanzwa uye [00:10:00] specificity? Zviratidzo izvi zvakawanda zvine high sensitivities, saka zvinowanzoonekwa. Saka tinozviona muvanhu vanopfuura hafu ye prodromal DLB cases, kunyanya kuvimbiwa kana orthostatic hypotension, asi zvine specificity yakaderera zvikuru kana tichienzanisa nezvimwe zviratidzo zvatinoona. Saka kuvapo kweREM sleep behavior disorder kana abnormal dopamine transporter imaging.

Uye zvakare, ndaizodzokera kuongororo yakataura nezvayo naAbhi, iyo yakanyatsoita kuti chirwere cheParkinson chiitike, tichitarisa IBD uye tichitevera boka iroro kwemakore akati wandei, izvo zvakatibatsira zvikuru. Ndinofunga kuti kune mamwe mabasa matsva kubva kuboka rekuBologna akaburitswa mu neurology gore rapfuura.

Uye vakatarisa kuti zviyero zvengozi zvaive zvekuchinja, kuchinja pheno. Uye zvakare, zviratidzo zvakafanana zvakabuda. Saka neurogenic orthostatic hypotension, blunted responses regal, zvinhu zvakakosha zvengozi yekufanotaura kuchinja pheno.

Dr. Michele Matarazzo: Uye zvino tichitaura nezvezviratidzo zvakasiyana-siyana zve [00:11:00] mune mamwe mabasa enyu, kusanganisira zvidzidzo zvinotarisa maitiro ekutanga asiri ekufamba kwemuviri uye maitiro ekufambira mberi, kusagadzikana kwekuzvitonga kunoonekwa pamwe chete nezviratidzo zvepfungwa dzepfungwa pane kungozviparadzanisa nevamwe. Zvino, munofunga here kuti kusagadzikana kwekuzvitonga parizvino hakuna kuenzana muhurongwa huripo?

Chekutanga, tichienzanisa nedementia, tiri kufunga nezvenzira dzisingashande dzekufamba netsoka. Munofunga kuti hatifungi zvakanyanya nezvekusashanda zvakanaka kwemuviri here? Kana muchida kutaura, Alison nezvehurongwa hwakaita seMDS research criteria kubva kuchirwere cheParkinson's.

Saka zvatova nekushanda kwemuviri kusina kunaka. Asi unofunga kuti nzira iyi inoratidza zvizere spectrum yatiri kuona iye zvino uye tiri kuziva zvakawanda, kunyanya kana tichifunga nezvemhando dzakasiyana uye ma phenotypes akasiyana ezvirwere zvemuviri zveLewy.

Dr. Alison Yarnall: Ehe, ndinofunga kuti mamiriro ezvinhu ari kuchinja uye ndinofunga kuti tiri kungozviona zvakanyanya. Uye ndinofunga kuti kana tikaongorora zvakadzama, tichaona izvi uye tinozviona kakawanda. Ini ndinofunga kuti [00:12:00] kune rumwe rutivi, zviratidzo izvi zvakawanda zvinowanzoonekwawo muvanhu vakuru uye zvinowanzoonekwa sezvatinokura.

Saka pane kupindirana uku pakati pekukwegura pamwe chete nepakati pechirwere chemuviri cheLewy.

Dr. Michele Matarazzo: Zvakanaka, ngatiendei pakuongorora chirwere. David, ndichadzoka kwauri. Ehe, munhu wese anonzwa akasununguka kutaura. Saka ndedzipi nzira dziri kubuda dzekuongorora mashandiro emuviri dzinopa vimbiso yakawanda yekuona chirwere cheprodromal?

Dr. David Goldstein: Ndinofunga zvakakosha kusiyanisa zviratidzo zvekiriniki kubva kune zve laboratory. Izvi zvakakosha. Saka kana zvasvika pa orthostatic hypotension, semuenzaniso, iyo yandinofunga kuti haina kuratidzwa zvakakwana. Imhaka yekuti vanachiremba vetsinga havafungi nezvazvo kunze kwekunge murwere aine chiratidzo.

Hazviwanzoitiki kuti zviratidzo zvemuviri zviongororwe nguva nenguva mukiriniki yeuropi. Saka zvechokwadi, uchaderedza kuwanda kweropa muropa [00:13:00] kana uchivimba nezviratidzo. Ini ndinofarira zvikuru biomarkers uye kune physiological, kune neurochemical, kune neuroimaging, kune micro neuroimaging biomarkers, uye zvese zvinoenderana neVenn diagram.

Kana zvasvika pakufunga nezvemuviri, ndinonyanya kufunga nezvezviratidzo zve diver reflex, sympathetic neural function. Kana zvasvika pakufunga nezve neurochemical, ndinofunga nezve CSF levels ye catecholamines uye metabolites dzavo. Handizive kuti pane zvakawanda zvekutaura nezvazvo kana zvasvika pakuongorora plasma, ngatitii, nezve catecholamines uye metabolites dzavo mumamiriro ezvinhu aya, kunze kwekukundikana kwe autonomic. Kana zvasvika pakufunga nezve neuroimaging, takatotaura nezve PET scanning uye munyika chaiyo une MIBG SPECT scanning yako, yakadaro, inotarisa moyo. Uye kana zvasvika pakuongorora micro neuroimaging, saka une ganda rako biopsies. Kuwedzera kune [00:14:00] neurochemistry nezve catecholamines, hongu pane synuclein seeding thing, iyo mukudzidza kwedu yaive yekufungidzira mukudzidza kwenguva refu.

Saka izvozvo zvinokoshawo. Saka sezvandiri kuona, kune nzvimbo dzakasiyana dze biomarkers, uye ndinotarisira kuti mune ramangwana pachava nekuchinja kubva pakuongororwa kwekiriniki chete nekuti ndinofunga kuti hazvina hanya uye hazvina kunyanya kutaurwa. Uye pachinzvimbo pachava nekusimbiswa kwakanyanya pane idzi nzvimbo dzakasiyana dze biomarkers.

Dr. Michele Matarazzo: Zvakanaka, saka ndisati ndaenda kuna Abhi, ndinoziva kuti munoda kuwedzera chimwe chinhu, asi regai nditaure zvishoma nezve biomarkers. Saka munofunga kuti tinofanira kushandisa biomarkers idzi nguva dzose mukurapa uye kana muchifanira kutaura kuti chimwe kana zviviri zvichava, kana kuti zvichava nemhedzisiro yakawanda mune ramangwana rekurapa kwedu ngatitii mumakore mashanu kusvika gumi, chii chamungasarudza?

Dr. David Goldstein: Ndingashandisa nzira ye [00:15:00]. Unotanga nezvinhu zvinokurumidza, zvakachipa, zvakachengeteka, asi zvinonzwisisika zvakakwana. Uye ndinofunga kuti kubva ipapo une ongororo yekuchinja kwekurova kwemoyo wako kunyanya munharaunda yema frequency.

Ndinofunga kuti ndizvo zvatakaona zvichiitika. Asi pane chinjana nekuti pane zvinhu zvakawanda zvakanaka zvenhema uye zvinhu zvisina kunaka zvenhema nezvimwewo zvakadaro. Mushure meizvozvo, ndinofunga kuti ndaizoenda kune chimwe chinhu chine chekuita nesynuclein.

Uye ndinofunga kuti munoziva zvandiri kutaura nezvazvo. Uye mushure meizvozvo, ndinofunga kuti ndaizoenda kuPET scanning, fluorodopa PET scanning yeuropi. Uye kana zvichigona kuitwa fluorodopa PET scanning yemoyo. Saka tinotanga kubva pane zvakachipa, zviri nyore, nekukurumidza, uye zvakachengeteka kusvika kune ndiani anoita izvozvo?

Dr. Michele Matarazzo: Ehe. Zvakanaka. Saka ndinoda pfungwa yealgorithm. Ipfungwa yakanaka kwazvo. Unofungei nezvaAbhi, uye waida kuwedzera chii pahurukuro ye biomarker.

Dr. Abhimanyu Mahajan: Saka chimwe chinhu chakafanana nezvakataurwa naDr. Goldstein, sezvandinofunga nezvazvo, ndinofunga kuti kuva nezviratidzo zvebiomarker zvakanangana zvakanyanya kwakakosha zvikuru kuti tinzwisise pathophysiology. Kwete pathophysiology chete, asi physiology yekuti zvese izvi zvinoshanda sei.

Panguva imwe chete, ndinofunga kuti pane zvakanaka zvakawanda mumaonero angu kuti tisazvidza kubatsira kwemubhedha nezvatingaita pamubhedha. Ndinobvumirana zvizere kuti kunyangwe orthostatic blood pressure, semuenzaniso, chidzidzo ichi chakaitika paYunivhesiti yeCincinnati makore mashoma apfuura ikozvino. Uye takatarisa varwere vaive ne orthostatic hypotension padivi pemubhedha.

Uye takavabvunza nezvezviratidzo zve orthostatic hypotension. Uye vanhu vanosvika 30% vaisaziva kuti BP yavo yaive orthostatic. Chinokosha ndechekuti, kunyangwe vasina ruzivo, kunyangwe vasina zviratidzo, njodzi yeADLs nekudonha kwakanyanya yaive ichiri yakakwira, handiti? Saka kungoti murwere haazvizivi hazvirevi kuti hazvina zvazvinobatsira. Panguva imwe chete, zvirinani mukiriniki yangu, ndinoedza nepese pandinogona napo kuva nechiyero chakaderera kuti ndiwane orthostatic blood pressure.[00:17:00] 

Kunyangwe zviratidzo zvisinganyanyi kunzwisisika, ndichiri kufunga kuti zvakakosha kuzvibata padivi pemubhedha. Ruzivo rwakawanda rwatinarwo nezvemhedzisiro yezviratidzo zve orthostatic uye kukanganisa kwazvinoita kune mamwe matunhu muParkinson's muzvidzidzo uye muma cohorts anoteverwa mukiriniki rwakavakirwa pazviyero zvakadaro, zvakaita seSCOPA nedzimwe. Uye kwete prodromal chete, ndinofunga kuburikidza nechirwere uri kutaura nezveParkinson's isina kukanganisa kwepfungwa, Parkinson's yakatangwa, uye kunyange varwere veDLB vakakura zvakare.

Saka zvinotevera mukufamba kwechirwere kwete chete muchirwere cheParkinson's uye zvinogona kubatsira pakurapa. Chinhu chekupedzisira chandinoda kuwedzera ndechekuti, ndinofunga kuti kugona kuita zviyero izvi uye kuongororwa uku padivi pemubhedha kunotipa mukana wekutora ruzivo kubva kumasaizi makuru izvo zvinotibatsira kunzwisisa kusiyana kwezvirwere zvatinoona.

Kunyangwe tichiedza sei kuita kuti mapoka aya ave chaiwo sezvinobvira, kuchine huwandu hwakakwana [00:18:00] hwekusiyana. Saka kuongororwa padivi pemubhedha kunotibatsira kuwedzera huwandu hwemuenzaniso. Uye zvakare zvinoita kuti zvive nyore kuverengerwa mumiedzo yekiriniki uye zvatinoziva nezvekiriniki.

Saka ndinofunga kuti nzira idzi dzese dzekuongorora kusashanda zvakanaka kwemuviri dzinofanira kushanda pamwe chete. Ehe, hadzina kubhadharwa.

Dr. Michele Matarazzo: Zvino regai ndikubvunzei imi vatatu, munofungei nezvekuongorora kwakakwira uye kunodhura uye tobva taenda padivi pemubhedha kuti tiite chimwe chinhu chiri nyore kuwana. Asi ngatiendei mberi totaura nezvekutarisa nguva dzose. Chimwe chinhu chatinogona kuwana zvakananga kubva kumurwere ari kure. Munofungei nezvemhando iyi yemidziyo mune ramangwana, kwete kungoongorora chete asiwo kunzwisisa zvinoitika kuvarwere ava, vangave vasiri nesu muchipatara kana mukiriniki yekutsvagisa, Alison.

Dr. Alison Yarnall: Ehe, ndiri kufarira zvikuru izvi uye ndinofunga kuti ndizvo zviri kuitika pasi rose. Pano muUK tine chirongwa chemakore gumi cheNHS yedu, chimwe chezvinhu zvitatu izvi [00:19:00] kufamba kubva kuchipatara kuenda kunharaunda, kurwara kuenda kukudzivirira, kutarisirwa kumba. Uye ndinofunga kuti iyi ndiyo nzira yatiri kuenda nayo kune chero matanho aya atiri kutaura nezvawo, pamwe chete nezvimwe zviyero zvakawanda, kurara, kuneta, kufamba, kufamba, uye kuziva kunyangwe. Kuyera izvi munzvimbo yemumwe munhu mukati memazuva manomwe zvinoreva kuti hatina mufananidzo usingazotore kuchinja kuripo kuri chikamu chechirwere cheParkinson nedementia Lewy bodies. Uye ndinofunga kuti apa ndipo patiri kuenda uye patiri kuenda.

Uye zvingangoderedza mutoro wenguva yechiremba. Kana tiine mhedzisiro yemurwere panguva chaiyo, tinogona kukwanisa kuchinja zviri kure kudzivirira vanhu kuti vasauye kukiriniki. Zvinobvumirawo kubatanidzwa. Saka varwere vakwegura, vasina simba, vanhu vari kumaruwa zvaizovabvumira kuwana rubatsiro rwakafanana nerwevaya vanogara pedyo nenzvimbo huru dzeyunivhesiti [00:20:00] mukiriniki uye munzvimbo yekutsvagisa.

Uye ndinofunga kuti iyi ndiyo nzira yatiri kufamba nayo, uye pamwe kwete kutarisa chinhu chimwe chete, saka kwete nzira yeunivar asi tichitora pamwe chete algorithm yakakurukurwa naDavid. Saka pamwe zviyero zvakawanda, orthostatic blood pressure, kushanduka kwekurova kwemoyo, nezvimwewo. Uye pamwe mamakisi uye kukwanisa kusiyanisa avo vanofambira mberi nekukurumidza, zvishoma nezvishoma, uye avo vanoda kupindira. Ndinofunga iyi ndiyo nzira yekufambira mberi.

Dr. Michele Matarazzo: Zvakanaka. Saka mubvunzo unotevera waive wekushandisa maturusi erudzi urwu pakusarudza njodzi uye pamwe kana kusashanda zvakanaka kwemuviri kunogona kutibatsira kuziva vanhu vari panjodzi huru yekuchinja maitiro avo vari munjodzi yechirwere cheParkinson kana dementia vane Lewy bodies.

Unoda kuwedzera chimwe chinhu pane izvi here? Pamwe David.

Dr. David Goldstein: Ndichataura nezve PD risk study nekuti ndeimwe yezvidzidzo zvishoma zve longitudinal perspective zvevanhu vane zvinhu zvakawanda zvinokanganisa kuti vaone kuti predictive value ndeyei [00:21:00] kuwedzera mhando dzakasiyana dze biomarkers. Ndinofunga kuti ndicho chinhu chakakosha che PD risk study chakaita kuti ive yakasiyana.

Kufanotaura, kwakavakirwa pazvinhu zvine njodzi, nhoroondo yemhuri, maitiro ekurota achitevedzera, kusashanda zvakanaka kwemafuta, kusashivirira orthostatic, zvinhu zvakadaro. Izvozvo zvakasimba kwazvo. Kunyanya kana zvakabatana. Wedzera zvakanyanya mhedzisiro yekufanotaura, yerudzi rwekufanotaura maererano nekushandurwa kwepheno mune ramangwana. Asi kana ukawedzera mune biomarkers, saka muchokwadi, haisi nyaya yenjodzi zvakare. Une chirwere. Inyaya yenguva. Uye ndinofunga kuti ndiyo yaive chidzidzo chikuru chekuenda nacho kumba kubva muongororo yePD risk. Izvo biomarkers zvichachinja njodzi, handizivi, kashanu kusvika zana muzana, ndizvo chete. Ndinofunga kuti ramangwana riri mukuwedzera mune biomarkers kunyanya dzemwoyo [00:22:00] kune zvinhu zvine njodzi zvatatotaura nezvazvo. Ndaida kutaura zvakare, ndichitevera pfungwa yekuita remote or online monitoring.

Ndinobvumirana nazvo, zvine simba chaizvo. Zvine simba guru. Uye ndinowedzerawo, kuyerwa kweBP nguva dzose kana kuyerwa BP nguva nenguva, kutarisa BP nguva nenguva, zvakadaro. Nekuti varwere vazhinji havana zviratidzo zve orthostatic, asi vane hypotension mushure mekudya yaunogona kuona.

Ndinofunga zvakakosha kuziva varwere kuti kana hypotension yavo ye orthostatic yakanyanya kuipa masikati. Nekuti kazhinji inoipa mangwanani, uye kana yakanyanya kuipa mangwanani, hausi kuzorapa munhu wacho nemushonga we vasoconstrictor nguva dzese.

Kuva nekutarisa ikoko kunogona kuongororwa uri kure, ndinofunga kuti ndiyo nguva yemberi.

Dr. Michele Matarazzo: Zvakanaka, saka ndinoona kuti tine vateveri vatatu vakuru ve biomarkers pano izvo zvakanaka. Uye ndinofungawo kuti meseji yekupedzisira yekuti ruzivo urwu runoshanda sei kune varwere chaivo [00:23:00] vakaita sewe vaitaura nezvaDavid nekuda kweBP. Icho chinhu chatinofanira kunyatso yeuka.

Mushure mekutaura nezvazvo, ndinoda kutaura zvishoma nezve pathophysiology. Zvino, pamwe Abhi, kana uchigona kutaura nezvazvo, kusashanda zvakanaka kwemuviri muchikamu cheprodromal chechirwere kunogona kutidzidzisei nezve pathophysiology iri pasi pezvirwere zvemuviri zveLewy?

Ehe unogona kutaura nezve chero chaunoda. Asi tanga tatotaura nezvemuviri uyu, hurukuro yepfungwa yekutanga. Unofungei nezveizvi?

Dr. Abhimanyu Mahajan: Chero bedzi ndine rezenisi rekufungidzira zvisina musoro, ndinogona kufungidzira zvichibva pane zvatinoziva. Asi kutaura kamwe chete pamusoro pezvakataurwa naDr. Yarnall kare. Handina kukwanisa kurega kunzwa godo re2% chete pavakataura kuti NHS ine chirongwa chemakore gumi chekubatanidza izvi nekuti ndinogona kukuudzai kuti parizvino tine chirongwa chekutsvagisa pakushandisa mamonitor eBP ambulatory panzvimbo yedu. Uye munguva pfupi yapfuura varwere vedu vaviri vakarasikirwa nemamonitor eBP uye iyoyo yaive $6,000. Uye ndichiri kutarisira kuti izvozvo zvinobva mubhajeti redu rekutsvagisa. Saka tiri kuedza kuita izvozvo nekuda kwezvikonzero zvese zvandakataura. Asi zvinofanira kubva murubatsiro kwete kubva mumari yehurumende.

Ndataura nezvazvo, ndinoenda kumubvunzo wako. Ndinofunga kuti kune humbowo hwakawanda hune musoro, kana husiri muchirwere cheprodromal, saka zvechokwadi muPD yekutanga uye DLB yekutanga nezvechingave chiri chikonzero chechirwere ichi.

Zvimwe zvacho ndezvekutanga, kutaura nezvekushaya simba kwemoyo uye kugona kuziva. Chinhu chakanyanya kundinetsa kutaura nezvacho i cerebral autonomics uye kukanganisa kwacho. Ndinoziva Dr. Rymans vakaburitsa izvi munguva pfupi yapfuura muMovement Disorders journal, asi paive neongororo yakanaka uye meta-analysis kwavakaratidza kuti paive nehukama hwakananga, kutaura chokwadi, vakaratidza chikonzero nekuti chaive nemhinduro yedose zvakare, pakati pekuchinja kweropa uye kufamba kweropa muuropi kune avo vane neurogenic orthostatic hypotension. Saka, kana uine kuchinja kweropa [00:25:00], unogona kuva nekuchinja kweropa muuropi, izvo zvinotsanangura zvimwe zvezviratidzo izvi zvatinoona.

Nyaya dzakatevedzana dzatakaburitsa munguva pfupi yapfuura muMDCP, takaona kuti muvarwere vana pakanga paine kudzikira kweBP mukati meawa imwe chete muchengeti wevarwere asati ataura nezvekuchinja-chinja kwepfungwa. Saka ndicho chimwe chezvikonzero zvacho. Ehe, locus coeruleus yanga iri nyaya inonyanya kutaurwa kwenguva yakareba, uye ndinofunga kuti iri kuwedzera mukurumbira munguva pfupi yapfuura.

Kuburikidza nekuburitswa kwe noradrenaline unogona kuva nemhedzisiro kwete chete pamaitiro e autonomic, asiwo pakutarisisa. Nenzira, izvi zvingasave zvakanangana nezvirwere zvemuviri zveLewy, asi zvechokwadi muzvirwere zvemuviri zveLewy kune cholinergic system, iyo zvakare, ndinoziva Dr. Yarnall akaburitsa pamusoro pekurasikirwa ne cholinergic drive. Mubvunzo we alpha synuclein deposition, kungave pakati kana kumativi, unogara uripo, uye handizive kuti hukama hwacho hwakanyatsoongororwa. Uye ndinofunga kuti zvechokwadi unofanirwa kudaro. Uye zvechokwadi sympathetic denervation, handiti? Izvo Dr. [00:26:00] Goldstein akakurukura pakutanga.

Saka iyi haisi rondedzero yakazara. Zvinogoneka kuti zvimwe zveizvi, kana zvese izvi zvine chekuita nezvirwere. Zvingangoita kuti musanganiswa wekuti ndezvipi zveizvi zvinobatanidzwa unosiyana zvichienderana nerudzi rwechirwere nerudzi rwemurwere. Saka ndinofunga kuti zvese izvi zvinoda kunzwisiswa kana tichida kutaura nezvekurapa kwemurwere kunoshanda kumurwere iyeye.

Dr. Michele Matarazzo: Zvakanaka. Zvakanaka, Alison naDavid, makataurwa naAbhi paakapindura. Saka kana muchida kuwedzera chimwe chinhu pane izvi.

Dr. David Goldstein: Kune mibvunzo miviri mikuru isati yambopindurwa kana zvasvika pakudzidza nezve pathophysiology. Wokutanga ndewekuti chii chinokonzera kushomeka kwe catecholamine? Kushomeka kwe putamen dopamine kwakanyanya, se 98%. Hapana imwe neurotransmitter, kune mamwe ma transmitter, hongu, anobatanidzwa, asi hapana chakaita se 98%. Chii chinokonzera izvozvo?

Pane mhando dzakasiyana dzema "reaction" dzinoitika mu "dopamine terminals". Ndedzipi dzadzo dzakakanganiswa? Mhedzisiro yacho [00:27:00] muhuwandu ihwohwo hwekushomeka. Mubvunzo wechipiri ndewokuti, chii chinobatanidza kushomeka kwe catecholamine neLewy bodies, kana kuti mune mamwe mazwi emazuva ano ne alpha synucleinopathy?

Sei zvakadaro? Izvozvo zvakatsanangurwa naTretiakoff makore anopfuura zana apfuura. Kubatana uku kuri pakati pemiviri yaLewy, yaakauya nayo sezita uye kubviswa kweganda muganda, uko kwava kunzi kushomeka kwedopamine, dambudziko remakemikari europi.

Chii chiri hwaro hwehurefu ihwohwo? Ndiyo mibvunzo miviri. Ndine mhinduro. Asi ikozvino zvese izvi inyaya yepfungwa. Haisi nyaya yedata rakajeka. Dai paine data rakajeka, ndaizowana mibairo kwese kwese. Iri ingori zano.

Pfungwa yacho ndeyekuti chinokonzera kushomeka kwe catecholamine inyaya yekusakwanisa kuchengeta catecholamines mu vesicles, [00:28:00] vesicular storage defect. Izvi zvinoitika, ndinofunga, pakutanga kwechirwere chisati chatanga. Ndinozviti zvinorwara, asi kwete chiitiko chakafa.

Uye chii chinobatanidza kushomeka uku ne alpha synuclein?

Izvi ndinofunga kuti zvinobva mukugadzirwa kwemetabolism ye catecholamines inonzi aldehydes, catechol aldehydes. Aldehyde ye dopamine inonzi DOPAL. Kana ikangoerekana yaita oxidize, inoderedza mafomu eprotein nesimba uye inobatanidza alpha synuclein. Ndinofunga kuti ndiyo link yacho.

Zvirwere zvemuviri weLewy hazvisi zvesynucleinopathies, chaizvo. Zvirwere apo alpha synuclein inosangana ne catecholamine metabolites, dzakadai seDOPAL. Uye kune humbowo hwakawanda hwepamberi pekiriniki nezvimwewo. DOPAL inowanikwa mu putamen postmortem zvichienzaniswa ne dopamine muchirwere cheParkinson.

Asi kuti [00:29:00] unyatsonyengetedza munhu asina chokwadi, unofanira kuita ongororo yekuti unopindira papi panyaya iyi wobva waratidza kuti kana ukadaro, hausi kutanga chirwere chacho. Uye izvozvo hazvina kuitika.

Dr. Michele Matarazzo: Uyewo, mubvunzo ndewokuti, sei izvozvo zvakaitika pakutanga?

Dr. David Goldstein: DOPAL iri kugadzirwa nguva dzese. Dopamine iri kugadzirwa nguva dzese. Saka inoonekwa semushonga we autotoxin. Haisi mhando yechinhu chinoonekwa nharaunda. Haisi chinhu che genetic. Ichi chikamu chehupenyu. Zvinoitika nguva dzese.

Mune vamwe vanhu, kana usingakwanise kubvisa chepfu mu aldehyde iyoyo, nekuti ngatiti une dambudziko re aldehyde dehydrogenase raunozvarwa naro, kana kuti uri kusangana nemushonga wezvipembenene unozodzivisa aldehyde dehydrogenase. Ndizvo zvinoita kuti dambudziko riripo re homeostasis rive chirwere.

Zvese izvi ndezvedzidziso, asi ndizvo zvandinofunga nezve pathophysiology.

Dr. Michele Matarazzo: [00:30:00] Zvakanaka. Alison, tisati tataura nezvekurapa, unoda here kuwedzera chimwe chinhu pa pathophysiology kana 

Dr. Alison Yarnall: Ehe, ndakangonakidzwa nehurukuro idzi uye kunzwa zvese nezvazvo.

Ndinofunga zvese izvi zvinongoratidza kuti Parkinson's, Lewy body diseases, DLB, zvese izvi zvine kusiyana kukuru uye pamwe kushomeka uku mu neurotransmitters dzakasiyana ndiko kunokonzera izvozvo.

Uye ndinofunga kuti kana tichienderera mberi nemubvunzo unotevera, unoratidza mhedzisiro yekurapa kweizvi. Saka pamwe mune ramangwana, munyika ino yakanaka ine zviratidzo izvi, murwere akapinda mukiriniki, wakakwanisa kuziva kana vakanga vasina ma neurotransmitters akasiyana-siyana, zviratidzo zve autonomic zvavaiva nazvo zvinogona kutsanangura kurapwa kwavo uye sarudzo dzavo dzekurapa. Pamusoro pezvo, ndinofunga kuti ndezvipi zviratidzo zve autonomic pro zvinogona kutiudza nezvezvirwere zve prodomal. Zvinogonawo kutipa pfungwa nezve njodzi uye kupatsanurwa kwenjodzi. Uye izvozvo zvinogona kupa rutsigiro kune waunoisa pamberi mukuyedzwa kwekiriniki.

Uye [00:31:00] zvichida kuyedzwa kwekupedzisira kwekiriniki kuchava chimwe chinhu chinodzivisa munhu kuchinja kubva kuchirwere cheprodromal kuenda kuDLB, PD inoratidzwa. Zvingangodaro nekuona izvi zviratidzo zvekiriniki uye zvebiomarker zvechirwere cheautonomic, zvinogona kutibatsira kusarudza kuti ndiani anopinda mukuyedzwa kupi kwekiriniki.

Dr. Michele Matarazzo: Zvakanaka, saka kushandisa zviratidzo zve autonomic dysfunction kuwedzera miedzo yekiriniki uye, tibatsirei kuti tiende kupfungwa iyi inozivikanwa uye inoshandiswa zvakanyanya pari zvino yekurapa kwakarurama, kuwana kurapwa kwakakodzera murwere akakodzera. 

Dr. Alison Yarnall: Zvakarurama. Ehe.

Dr. Abhimanyu Mahajan: Ndingawedzera pfungwa imwe chete pane izvozvo here?

Dr. Michele Matarazzo: Ehe, Abhi.

Dr. Abhimanyu Mahajan: Ehe, ndinofunga kuti kuwedzera miedzo yekiriniki ndiyo nzira chaiyo yekutevera, asi ndingatiwo zvino zvatava kuziva kuti kusashanda zvakanaka kwemuviri kwekutanga kunobatanidzwa nenguva inokurumidza yekuchinja kwe pheno, kunobatanidzwa nezvirwere zvakawanda, kupona kushoma, pamwe nenjodzi huru yekuziva. Kunyangwe kana tisiri kushandisa [00:32:00] mutoro wekuzvitonga semhedzisiro, hatisi kushandisa mutoro wekuzvitonga kunowedzera miedzo yekiriniki. Ndinofunga zvakakosha zvikuru kupatsanura muenzaniso mumiedzo yekiriniki nekuti zvatinofunga sedata repamutemo maererano nekumhanya kwekufambira mberi nezvimwe zvakadaro. Zvakasiyana zvikuru kune avo vane kusashanda zvakanaka kwemuviri.

Uye hukama hwekupindura kwedosi. Semuenzaniso, mukukundikana kwe autonomic chaiyo, boka rekucherechedza remakore gumi rakaburitswa kubva kuUCL pakutanga kwegore rino, varwere 281. Saka harisi boka diki. Kukura kwekushomeka kweropa mumuviri kwaive chimwe chezvinhu zvine njodzi kurufu, kuhupenyu, uye kukurumidza kufambira mberi.

Saka zvakakosha kuti zvinhu izvi zvifungisiswe kuti unzwisise kuti chii chinonzi quote uncounte data rakajairika kana kuti rinogara riripo mumurwere wako wepakati akanyoreswa mune chero chezvidzidzo izvi. Ndinofunga kuti ipfungwa inokosha yekunzwisisa.

Kana zvisina kudaro, kunzwisisa kwekuchinja kwechirwere, semuenzaniso, tinowanzo enzanisa magirafu uye kutarisa nguva [00:33:00] kuti tizadze nzvimbo isina chinhu, handiti? Uye kana izvozvo zvichisiyana nekuda kwekuvapo kwemutoro wekuzvitonga, saka ndinofunga izvozvo zvinofanira kufungwa nezvazvo.

Dr. Michele Matarazzo: Saka tichishandisa ruzivo rwatinarwo nezvezviratidzo zvekufungidzira zvezviratidzo izvi tozviisa muongororo yemigumisiro yemiedzo yekiriniki. Ndinofunga kuti izvozvo zvingave chinhu chinonakidza zvikuru. Ndatenda zvikuru. Tave nehurukuro inonakidza uye inoshamisa, saka ndinoda kukutendai zvechokwadi.

Tisati tapedza, ndinoda kukubvunzai mubvunzo wekupedzisira, mubvunzo mumwe chete kwamuri vatatu. Uye zvakare, ndichatanga naDavid. Munofungei kana kuti chii chamunoona sechinonyanya kukosheswa mundima iyi mumakore mashanu kusvika gumi anotevera?

Dr. David Goldstein: Kuziva zviratidzo zve preclinical.

Pfungwa yacho ndeyekuti kunyangwe uine chirwere chekubereka mwana, pane kukuvara kukuru kwatovepo. Kana ukava nedambudziko rekuziva, kana ukava neParkinsonism isingaonekwe, ndizvozvo. Ini ndinofunga kuti tariro yeramangwana re[00:34:00] ndeyekuziva maitiro echirwere munhu asati ava nezviratidzo zvachose. Uye chinangwa hachisi chekurebesa nguva yechirwere. Zvakasiyana. Chinangwa ndechekunonotsa kutanga kwechirwere. Munhu wese achafa.

Asi kana ukakwanisa kuwedzera nguva yehutano hwako kwehupenyu hwako, ndicho chinangwa chevanhu. 

Dr. Michele Matarazzo: Zvakakwana. Waita basa. Zvino, Alison, chii chaunonyanya kukoshesa pakutsvaga ruzivo mumakore mashanu kusvika gumi anotevera?

Dr. Alison Yarnall: Ndinofunga kuti kugadzirisa zviratidzo izvi zvakaoma kurapa zvemuviri kwakakosha. Pane hama iri muhumbowo huripo parizvino, uye kazhinji kacho kukanganisa hupenyu hwemunhu zvakanyanya. Saka ndicho chinhu chandinonyanya kukoshesa pakutsvaga.

Dr. Michele Matarazzo: Zvakanaka, Abhi.

Dr. Abhimanyu Mahajan: Ini ndinofunga kwandiri, mumakore mashanu kusvika gumi anotevera, kana paine mutoro wekuzvitonga wakakodzera kumurwere wese ane synucleinopathy anouya kukiriniki, kungave [00:35:00] murwere weprodromal, PD yekutanga, DLB yekupedzisira, chero bedzi uchikwanisa kuibata nemazvo uye kurapa zviratidzo izvozvo, kwete chete nekuda kwemhedzisiro yezviratidzo izvozvo asiwo, uye uyu mufananidzo wepasi rose wekudzivirira zviratidzo zvine chekuita nazvo mune ramangwana. Ndinofunga kuti ndicho chaizova chinhu chekutanga kwandiri. Kunyanya, ndinofunga kuti kukanganisa kwepfungwa, hatina zvinhu zvakakwana mudura redu rekurwisa kukanganisa kwepfungwa.

Uye ndinofunga kuti mutoro wekuzvitonga, mutoro wemwoyo, ndechimwe chezvinhu izvozvo. Zviri pamberi pedu chaipo. Tinofanira kuita basa riri nani mukuratidza kupindira kunotungamira mukuvandudza kugona kwepfungwa. Kunze kwezvatinogona kufungidzira kubva muzvidzidzo zvine chekuita nepfungwa, izvozvo ndizvo zvakanyanya kukosha kwandiri.

Dr. Michele Matarazzo: Iyi yave hurukuro inonakidza zvechokwadi, saka ndinoda kukutendai imi vatatu. Ndatenda, David. Ndatenda, Abhi. Ndatenda, Alison, nekundibatana nhasi.

Dr. Alison Yarnall: Kutenda nekuve neni.

Dr. David Goldstein: Zvinofadza.

Dr. Michele Matarazzo: Uye ndinodawo kukutendai zvechokwadi, Sephira Ryman neMDS Scientific Issues Committee [00:36:00] nekubatsira kugadzira chikamu chino. Sechiyeuchidzo, hurukuro iyi ichaburitswawo seblog post pawebhusaiti yeMDS, yakarongwa uye yakagadziriswa naSephira.

Uye kana makanakidzwa nechikamu chino, musakanganwawo kunyorera kuMDS podcast. Uye tinotenda mese nekuteerera.