Curs Neuroinfectii

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NEUROINFECIIBogdan O. Popescu, MD, PhD Clinica de Neurologie S.U.U.B U.M.F. Carol Davila Bucureti

SINDROAME Localizare spaii LCR + leptomeninge (meningita) sistemul ventricular (ventriculita) substana cenuie i alb a encefalului (encefalita) maduva spinrii (mielita) infecia focal bacterian la nivel cerebral = abces cerebral (faza encefalitica / faza de colectare) ntre dura mater i arahnoida = abces (empiem) subdural n afara durei mater = abces (empiem) epidural

http://www.umm.edu/neurosciences/neuro_infect.html

Evoluie manifestri clinice acute (meninigite purulente, listerioza SNC, encefalita herpetica, etc.) manifestri clinice subacute (abces cerebral, encefalita focal, neuroborelioza, neurosifilisul, meningita tuberculoas, neurobruceloza, actinomicoza, etc.) manifestri clinice cronice (meningita tuberculoas, neurosifilisul,

neuroborelioza, boala Creutzfeldt-Jakob, etc.)

Epidemiologie sporadice endemice epidemice

Manifestri clinice meningita i encefalita apar rar n forma pur examenul LCR stabileste diagnosticul manifestri specifice grupelor de pacieni: nou-nscuii: agitaie, abandonarea suptului, febr sau hipotermie, agitaie, tulburare de ritm respirator, crize epileptice, bombare de fontanel btrnii: febr, tulburri de comportament, sindrom confuzional, crize eplieptice, astenie, alterarea strii de constien pn la com imunodeprimaii: febr, cefalee, redoare de ceaf, somnolen + semnele afeciunii de baz

Sindromul meningeal febr sever cefalee intratabil / durere radicular fotofobie / fonofobie grea / vrsturi alterarea strii de constien redoare de ceaf / durere la flexia capului (iritarea leptomeningelui) postura in hiperextensie / opistotonus semn Kernig: rezistena la ridicarea membrului inferior cu genunchiul in extensie semn Brudzinski: flexia involuntara a membrelor inferioare produsa de flectarea capului

http://www.umm.edu/neurosciences/neuro_infect.html

http://www.umm.edu/neurosciences/neuro_infect.html

Sindromul encefalitic cefalee febr crize epileptice (adesea focale) semne focale neurologice (deficite n sfera nn. cranieni III, IV, VI, VII, afazie, hemiparez, piramidalitate, hemianopsie, ataxie, coreoatetoz) tulburri de comportament alterarea strii de constien (agitaie, iritabilitate, confuzie, somnolen, letargie, com) semnele neurologice pot fi precedate de: mialgii/artralgii, subfebr, stare de prostraie

Encefalita - forme speciale cerebelita acut (infecii virale: varicella-zoster, EB, rubeolos, gripal, CMV, echo, coxsakie, HSV mai ales la copii) ataxie, astazo-abazie

encefalita de trunchi cerebral oftamoplegie, parez facial, dizartrie, disfagie, ataxie, hipoacuzie rar: encefalite bacteriene (Legionella, TBC, Listeria, Brucella)

Sindromul mielitic durere local sever paraparez (tetraparez) parestezii tulburri sfincteriene (retenie acut / incontinena prin preaplin) nivel de sensibilitate instalare a deficitelor n ore (acut) sau zile (subacut) diferite sindroame n funcie de localizarea leziunii

Mielita transvers exemplu RMN

www.uiowa.edu

CLASIFICAREA MIELITELOR MIELITE VIRALE enterovirusuri v. varicelo-zosterian HIV v. EB, CMV, HSV v. rabic v. gripal japonez HTLV-1

MIELITE SECUNDARE BOLILOR BACTERIENE, FUNGICE, PARAZITARE SI GRANULOMATOASE Mycoplasma pneumoniae B. Lyme mielite piogenice abcesul epidural acut si granulomul epidural abcesul spinal

MIELITE INFLAMATORII NON-INFECIOASE mielita postinfecioas i postvaccinal SM mielita necrozant subacut mielopatia LES i din alte vasculite mielopatia i poliomielita paraneoplazic

mielita TBC morbul Pott meningomielita TBC tuberculomul medular

infecii parazitare i fungice mielita sifilitic meningoradiculita cronic (tabes dorsalis) meningomielita cronic sifilisul meningo-vascular meningita gomatoas pahimeningita spinal cronic mielita sarcoidotic

PATOGENEZA Germenii patogeni pot ajunge la nivelul SNC extensie local de la un focar infecios apropiat cale venoas (sinuzita, mastoidita cel mai frecvent infectii otice) traumatism local prin nsmnare hematogen de la un focar la distan abilitatea de a disemina hematogen depinde de virulena germenilor Imunocompetena gazdei

diferite ci de a depi BHE centripet de-a lungul nervilor cranieni sau periferici (ex. HSV, v. varicelo-zosterian, v. rabic) endocitoz (Neisseria meningitiditis) transport intracelular (P. falciparum via hematii, T. gondii via macrofage) invazie intracelular (H. influenzae) pot ajunge n spaiul subarahnoidian pe la nivelul plexului coroid, sinusurilor venoase sau plcii cribriforme

la nivelul spaiilor subarahonidiene - rspuns inflamator (eliberare de factori ai complementului, citokine, influx de leucocite si macrofage, activarea microgliilor si astrocitelor) componenta encefalitic a sindromului meningeal alterarea integrittii BHE influx de lichide si proteine de-a lungul endoteliului vascular i n interiorul SNC, declannd edemul cerebral vasogen HIC leziuni cerebrale ischemice, metabolice, hipoxice necroza focal, infarct cerebral

INFECTII BACTERIENE

MECANISME PATOGENICE N MENINGITELE BACTERIENE1.

INFLAMATIA MENINGEAL ACUTarahnoidita pura encefalopatia subpiala afectarea inflamatorie / vasculara a rr. nn. cranieni tromboza vv. meningeale epidurita, plexita coroidal hernie de esut cerebral

2.

MENINGITE SUBACUTE SI CRONICEhidrocefalie hipertensiv infiltrare subdural (sd. HIC + tablou infecios) infarcte extensive arteriale si venoase

3.

SECHELEfibroza meningeala (arahnoidita opto-chiasmatica, meningo-mielita) meningo-encefalita cronica cu hidrocefalie hidrocefalia persistenta a copilului

ETIOLOGIA MENINGITELOR BACTERIENE Germen patogen Pneumococ (S. pneumoniae) Meningococ (N. meningitidis)

Poarta de intrare mucoasa nazala/faringeala, TCC, neurochirurgie, drenaj LCR nazofaringe

H. influenzae Listeria

nazofaringe

tract gastrointestinal

Stafilococul auriu M. tuberculosis

endocardita, TCC, drenaj LCR, punctie lombara, tract urinar TBC extracerebral

Examenul LCR n meningitele bacteriene esenial pentru diagnostic pleiocitoz 1.000-10.000 neutrofile 90%, cu timpul creste procentul de mononucleare presiune LCR crescuta LCR turbulent, purulent hipeproteinorahie (100-500 mg/dl) glicorahie scazut (sub 40 mg/dl) coloratii Gram din sedimentul LCR culturi din LCR, antibiograma ELISA, RIA, contraimunoelectroforeza, PCR

http://www.umm.edu/neurosciences/neuro_infect.html

TRATAMENTUL MENINGITELOR BACTERIENE

penicilina G, ampicilina, cefalosporinele nu trec BHE indemna dar trec BHE cu inflamaie vancomicina cloramfenicol trece BHE pericol de aplazie medular - de rezerva

Meningita purulent

ABCESUL CEREBRAL (I) debuteaz ca o cerebrit (faza encefalitic) apoi stadiul de abcedare (regiune ncapsulat de necroz purulent cu edem perifocal) diseminare a germenilor patogeni local (mastoidit, otit medie, sinuzit, osteomielit) localizare temporal cel mai frecvent nsamnare la distan (endocardit, pneumonie, infecie dentar, diverticulit, pacieni cu malformaii cardiace severe tetralogie Fallot, fistule AV pulmonare) eventual embolii multiple tablou clinic de encefalit la pacient cu endocardit inoculare direct (traum, intervenie neurochirurgical)

ABCESUL CEREBRAL (II) Manifestari clinice: cefalee great, vrsturi febr alterarea strii de contien crize epileptice focale / generalizate redoare de ceaf semne neurologice focale

Diagnostic: RMN/CT cerebral confirmare prin culturi din LCR

Tratament: antibiotic chirurgical de luat in considerare la cele unice si superficiale

ABCES CEREBRAL -CT

ABCESE CEREBRALE IRMStafilococ auriu BK

T1 cu contrastwww.ispub.com/journal

ALTE TIPURI DE ABCESE subdural (glicorahia scazut) peridural (LCR poate fi normal) complicaii ale meningitelor purulente sau post TCC abces medular: paraparez la un pacient cu focar infecios

Neuroborelioza (boala Lyme)

Patogeneza:

B. burgdorferi transmis prin capue (Ixodex ricinus) probabilitatea infeciei e mic (1-2% din oamenii mucai se infecteaz) incubaie 3-30 de zile afeciunea are 3 stadii

Manifestari clinice: stadiul I (infecia localizat): 90% din pts dezvolt macul sau papul eritematoas nedureroas - treptat se deplaseaz de la locul iniial form inelar erythema chronicum migrans + diseminare patogen (febr, astenie, artralgii, mialgii, alte sindroame algice + mai rar adenopatii regionale sau generalizate; toate aceste semne dispar spontan

Manifestri clinice: stadiul II (infecia diseminat): 10-15% dezvolt simptome generale (astenie, anorexie, artralgii, mialgii, cefalee, subfebr, discret opoziie a cefei) + manifestri cardiace (miocardita, pericardita, bloc AV) + manifestari neurologice ( pareze de nn. cranieni, poliradiculit dureroas, meningit limfocitar, dureri radiculare importante, deficite neurologice variate motorii, senzitive, atrofie muscular) + meningita Lyme (cefalee moderata, durere cervicala), LCR cu pleiocitoza mononucleara, hiperproteinorahie, glicorahie normala + rar encefalita (deficite neurologice focale, tulburare de concentrare, modificari de personalitate, depresie), RMN leziuni de substan alb)

stadiul III (infecia persistent) - rar - latena 1-17 ani (neuroborelioza cronic, encefalomielita Lyme) deficite neurologice ataxie, pareze de nn cranieni, para/tetraparez, incontinen urinar, encefalopatie (tulburri de concentrare si memorie, insomnie, astenie, depresie) + miozit + vasculit cerebral + acrodermatita cronic atrofic

Boala Lyme Diagnostic lipsa anamnezei muscaturii de capu (?!) eritemul cronic migrator e un semn clinic relativ constant confirmarea infeciei prin ELISA sau culturi, PCR examenul LCR: meningita limfocitar

Tratament Ceftriaxona sau cefotaxim (Rocephine) pt 2-3 sptmni

Mycoplasma pneumoniae determin o meningoencefalit sever sindrom cerebral, cerebelos, de trunchi cerebral sau spinal n timpul sau dup pneumonie/traheobronit cu mycoplasma coreoatetoz, convulsii, delir, hemipareza, edem cerebral encefalomielit postinfecioas sau leucoencefalit hemoragic (mecanism direct sau mediat imun) LCR clar, pleiocitoza limfocitar moderat, proteinorahie moderat crescut, glicorahie normala sau moderat scazut tratament: eritromicina sau tetraciclina

Neuroinfecia tuberculoas forme: meningita (meningita bazala tipica), meningoencefalita, tuberculom cerebral (semn de focar), mielita, mieloradiculita, arahnoidita opto-chiasmatica factori de risc: istoric de TBC, alcoolism, terapie cortizonica, HIV, imunodepresie, arie endemica nsmnare n parenchimul cerebral prin microtuberculi i n LCR, la nivelul arahnoidei proteinorahie foarte crescut, fibrina foarte crecuta in LCR (semnul vlului!)

Neuroinfecia tuberculoas simptome: febr, sindrom confuzional, cefalee, redoare de ceaf, debut insidios, pe parcursul a 2 sptmni histopatologic: exudat n spaiul subarahnoidian, bazal, cu meningoencefalit bazal, neuropatii de nervi cranieni, arterite, posibil tromboze, obstrucia cisternelor bazale, posibil hidrocefalie prognostic: 10-33% (!) din pts mor in ciuda tratamentului tratament 3-4 tuberculostatice (hidrazida, rifampicina, pirazinamida, etambutol) nu streptomicina (nu trece BHE)

http://www.granuloma.homestead.com/TB_extrapulmonary_gross.html

Sag. T1 & T2 WI: florid lumbosacral tuberculosis (Pott's disease) with epidural and sacral abscesses

Neurosifilisul Patogeneza: Treponema pallidum trei stadii Perioada asimptomatica (luni - ani = sifilis latent), apoi apar manifestari clinice, cum ar fi goma (tegument, oase, rinichi, ficat) leziuni cardiovasculare (anevrism de aorta)

Manifestri clinice: TP poate invada SN n orice stadiu al bolii, fr s genereze neaprat simptome Meningita precoce rar - deficite n sfera nervilor cranieni (n.VIII surditate brusc instalat, n.VII pareza faciala, n. II AV) LCR pleiocitoz limfocitar (100-400 celule/microlitru) i hiperproteinorahie Meningita asimptomatic de obicei - modificari LCR fr sindrom meningeal

Sifilisul meningo-vascular cefalee, tulburri de AV, vertij 5-12 ani de la infecia initial vasculita duce la AVC multiple ischemice, mai ales n teritoriul ACM i a vaselor mici perforante + afectare de nn cranieni (VIII, VII, V) + hidrocefalie + modificri de personalitate, crize epileptice, semne de suferin medular (paraparez, sindrom medular anterior, incontinen urinar) VDRL pozitiv n LCR Paralizia progresiv meningoencefalita cronic cu paralizie progresiva la 10-25 de ani de la infectare demen, tulburri mnestice, de personalitate, dizartrie, disfazie, tremor, apraxie, tulburri de mers, incontinen urinar, RFM abolit (pupile Argyll-Robertson) Tabes dorsalis complicaie meningo-vascular tardiv 25-30 de ani de la infecie manifestri oculare (strabism, modificari pupilare, atrofie papilara), sindrom hiperalgic (dureri lancinante n membrele inferioare, tulburri de mers (deficit de propriocepie), disfuncie autonom (impoten, incontinen urinar), deformri articulare

Tratament: penicilin

Cerebral atrophy, most prominent in frontal lobes seen in general paresis (a form of neurosyphilis).

medic.med.uth.tmc.edu/ edprog/Path/InfDis.htm

Cross section of spinal cord showing Wallerian degeneration of the dorsal or posterior columns that is seen in Tabes dorsalis (a form of neurosyphilis)

medic.med.uth.tmc.edu/ edprog/Path/InfDis.htm

INFECII VIRALE

TIPURI DE NEUROINFECII VIRALE MENINGITE (LCR clar !) ENCEFALITE MIELITE MIELORADICULITE ENCEFALOMIELITE primare (cale direct tropism pentru SN) secundare (focar la distan, mediate imun) Tipuri de virusuri: -arbo, -entero, varicelo-zosterian, HSV, EB, gripale, v. rabic)

Examenul LCR n meningita viral pleiocitoz (mononucleare) (zeci-sute) discret proteinorahie (50-100 mg/dl) glicorahie normal LCR- ap de stnc meningita tuberculoasa (glicorahie scazut, proteinorahie crescuta) meningita carcinomatoas meningita Lyme meningita din vasculite i boli granulomatoase

Alte cauze de meningite cu LCR clar:

ENCEFALITA HERPETIC Patogeneza HSV1 n copilarie leziuni ale mucoasei orale gg. trigeminal acces centripet SNC dormant reactivare (imunodepresie, afectiuni febrile, UV) herpes labial, keratoconjunctivit, encefalit (NC I i V) nu exista asociere intre herpes labial si encefalit HSV2 gg. lombosacrai prin transport axonal de la nivelul infeciei urogenitale (posibil asimptomatic) la adult meningit aseptic, poliradiculit, mielit la nou nascut encefalit encefalita HSV1 extrem de rar la nou-nascuti, encefalita HSV2 exterm de rar la aduli

Semiologie inflamaia prilor mediale i caudale ale lobilor temporali i frontali prodrom: febr, cefalee, grea, anorexie, letargie cteva zile simptome focale: halucinaii olfactive / gustative, afazie, tulburri de comportament (confuzie/psihoz), crize epileptice focale sau partiale complexe cu generalizare secundara, HIC (cu alterarea contienei pn la coma), redoare de ceaf, sindrom piramidal ex LCR: pleiocitoz limfomonocitar, hiperproteinorahie moderat, glicorahie normal, uneori xantocromie sau eritrocite numeroase (encefalita necrozant hemoragic), PCR

EEG: unde ascutite, hipervoltate periodice si complexe de unde lente cu frecventa de 2-3 Hz, focal sau difuz, mai ales la nivel temporal CT normal sau hipodensitate discreta temporobazala fara captare de contrast RMN T2 hiperintensitate precoce

Tratament aciclovir injectabil 10 mg/kgc x 3/zi 2-3 sptmni esenial administrarea ct mai precoce anticonvulsivante

ENCEFALITA HERPETICA

INFECIA CU HIV nu exist pacient n stadiul de SIDA care s nu aib afectare neurologic afectare neurologic: generat de HIV generat de infectii cu agenti patogeni oportuniti de la encefalita la poliradiculonevrit poate mima orice afectiune neurologic

encefalopatia HIV mecanismul patogenic nu este direct HIV modific sinteza proteic apare sinteza unei peptide la nivelul esutului cerebral care se comport ca un agonist de receptor NMDA apare neuroexcitotoxicitate prin fals neurotransmitor

COMPLICAII NEUROLOGICE IN INFECTIA CU HIV-1 (I)

1. CEREBRALE Predominant nonfocale complexul SIDAdemen encefalita acuta HIV encefalita cu CMV encefalita cu v. varicelozosterian encefalopatii metabolice

Predominant focale toxoplasmoza cerebral limfomul primar SNC leucoencefalita multifocala progresiva (LEMP) criptococoza abces / tuberculom cerebral neurosifilisul tulburri vasculare endocardita nonbacterian si hemoragia cerebral asociate cu trombocitopenia

COMPLICAII NEUROLOGICE N INFECIA CU HIV-1 (II)2. MEDULARE

mielopatia vacuolar mielita cu HSV sau zosterian

3. MENINGEALE

meningita aseptic (HIV) meningita criptococozic meningita TBC meningita sifilitic meningita limfomatoasa metastatic

COMPLICATII NEUROLOGICE IN INFECTIA CU HIV-1 (III)4. RDCINI SI NERVI PERIFERICI

sunt infecioase (HIV, v. varicelo-zosterian, CMV) forme:polineuropatia acut i cronic HIV poliradiculopatia lombar cu CMV mononevrita multiplex polineuropatie demielinizant senzitivo-motorie polineuropatia senzitiv dureroas distal

5. MUSCULARE polimiozit i alte miopatii (induse inclusiv de medicamente)

Figure 1. HIV encephalitis in a 35 year-old man. Hyperintense lesions are noted on this conventional spin-echo T2WI, located in the periventricular white matter and centrum semiovale, with relative sparing of the subcortical (arcuate) U-fibers. The lesions are "fluffy" or "cotton-like" and poorly circumscribed, showing confluence and a diffuse appearance. Cortical atrophy is apparent as indicated by enlargement of the subarachnoid spaces (cortical sulci) and lateral ventricles. The central atrophy is especially prominent. The white matter lesions were poorly appreciated on T1WI (not shown) and nonenhancing (not shown). There is no associated mass effect.

Rohit Bakshi Buffalo Neuroimaging Analysis Center, University at Buffalo, State University of New York, Buffalo, NY

Figure 2. Toxoplasmosis in a 44-year-old man with AIDS and a CD4 count of 91 presenting with several days of generalized weakness, malaise, fever, headaches, and new onset seizures. Serial studies are shown before and after antibiotic therapy (adapted in part from reference 7). (A-C) Initial scans, pretreatment. Edematous lesions appear centrally hypodense on CT (A) and centrally isointense to hypointense on T1WI (B) and hypointense to markedly hyperintense on T2WI (C), exerting moderate to severe mass effect. Severe surrounding edema is noted which is much larger than the size of the lesions. On T2WI (C), a central and concentric hypointense core gives a "target" appearance to the lesions. A third subtle lesion is apparent on T2WI in the thalamus (C). Note the relatively poor sensitivity of CT vs. MRI for the lesions in the left hemisphere. After contrast administration on both CT (A) and MRI (B), avid ringlike and nodular enhancement is noted. (D) T2WI shows marked improvement in each of the lesions 2 weeks after the completion of antitoxoplasmosis medical therapy.

Figure 3. Primary CNS lymphoma in two patients with AIDS. Adapted from reference 7. A-B. 24 year-old man with AIDS and hemiparesis, headaches and visual symptoms. Postcontrast T1WI (A) FLAIR (B) and T2WI (Figure 4) show a solitary large ring-enhancing lesion with mild mass effect and moderate vasogenic edema. The hypointensity of the lesion on T2WI (Figure 4) is characteristic of lymphoma. Note that the mass effect and edema is less than expected given the size of the lesion, as is typical for primary brain lymphoma while much more edema and mass effect vs. lesion size is expected in toxoplasmosis (Figure 2). C-D. 30 year-old man with AIDS. Postcontrast T1WI (C) and T2WI (D) show left temporal lobe vasogenic edema, related to a temporal lobe mass lesion (not shown). There are also bilateral lesions in the caudate nuclei on T2WI (D), with periventricular and ependymal extension of enhancement on the right (C). The ependymal spread is characteristic of primary CNS lymphoma.

Figure 5. Progressive multifocal leukoencephalopathy (PML) in 3 patients illustrate typical findings, including lesions that are markedly hypodense on CT (A), and hyperintense on FLAIR (B) and T2WI (C). As is characteristic of PML, lesions were markedly hypointense on T1WI and nonenhancing (not shown). Lesions follow the gray-white interface and prominently involve the subcortical U-fibers, while sparing the cortical ribbon, causing a "scalloped" or "heart of the gyrus" appearance.

Figure 6. Aspergillus cerebritis: serial noncontrast CT in a fatal case. Bilateral intermixed hypodense and hyperdense lesions are seen in the bilateral frontal, parietal and occipital lobes. Hyperdense areas represent hemorrhage. Hypodense areas represent varying degrees of ischemia/infarction, cerebritis, and edema. The two scans are separated by three days. A. Original scan. Note that the repeat CT (B) shows the emergence of diffuse brain edema (note loss of sulcal and gray/white definition). Autopsy revealed systemic and multiorgan aspergillus infection with multiple brain abscesses, angioinvasion and hemorrhage.

Figure 7. Cryptococcal brain infection. T2WI of a 33 year-old woman with AIDS shows multiple tiny bilateral hyperintense lesions in the caudate and putamen. These lesions represent mucoid material secreted by the fungal organisms.

Figure 8. Tuberculosis of the brain with cerebritis and tuberculoma formation. MRI scans of a patient are shown including postcontrast T1WI (A) and T2WI (B). Heterogeneous lesions are seen in the frontal and parietal region, involving both cortical and subcortical areas. The intermixed hypointensities on T2WI most likely represent hypercellularity, free radicals, or both. Postcontrast axial T1WI shows parenchymal and leptomeningeal enhancement, representing both meningitis and sub-pial extension.

BOLILE PRIONICE encefalopatii spongiforme transmisibile

se transmit la oameni prin esut infectat sau instrumente chirurgicale infectate particule proteinacee (prioni) mutaii la nivelul proteinei prionice (PrP) cazuri cu transmitere genetic PrP normala (PrPc) dup sintez transportat la nivelul membranei celulare i apoi returnat intracelular prin endocitoz lizat de proteaze o alt fraciune napoi n mb celular funcie fiziologic nc necunoscut protein ubicuitar, abundent n neuroni

gena PrNP cr. 20 mutaii cazuri genetice (PrP) PrPsc forma mutant encefalopatie spongiform infecioas induce conversia PrP la PrPsc PrPsc ajunge n SNC pe cale axonal retrograd sau pe cale limfocitar PrPsc i PrP nu pot fi lizate de ctre proteazele intracelulare i se acumuleaz intracelular modificri neuropatologice, moarte neuronal

CJD boala Gerstmann-Straussler-Scheinker insomnia fatal familial

CJD (Creutzfeldt Jakob)incidena 1/ 106 aduli, 60 de ani 90% sporadice, 10% familiale, foarte rare iatrogenice progres rapid, 4-12 luni deces precoce: astenie, vertij, tulburare cognitiva, anxietate, insomnie, halucinaii, apatie, depresie demen rapid progresiv, mioclonii, rigiditate, atrofie, fasciculaii, ataxie cerebeloas, tulburri de AV tardiv: mutism akinetic, mioclonii severe, crize epileptice, disfuncie autonom

EEG: complexe periodice bifazice sau trifazice de unde ascutite 1Hz CT atrofie corticala RMN T2 hiperintensitate la nivelul gg bazali LCR: enolaza neuron-specific, S100, tau, 14-33