NIGHTM ARES WITHOUT ATONIA AS AN EARLY
SYM PTOM OF DIFFUSE LEWY BODIES DISEASE
Paulo Robert o de Brit o-M arques
1, Robert o Vieira de M ello
1,2, Luciano M ont enegro
1,2ABSTRACT - A m ale 70 years old p atient w ith d iffuse or “p ure” Lew y b od y d isease is d escrib ed . The d iag nosis w as m ad e b ased on clinical features of nig htm ares w ith no atonia, attention d eficits w ith fluctuation in co g n it ive fu n ct io n , in ca p a cit y t o fin d h is w a y a ro u n d t h e n eig h b o u rh o o d a n d o t h er fo rm erly fa m ilia r environm ents and m ild neurop sychiatric sym p tom s. Neurop sycholog ical assessm ent showed m em ory d eficits, visuospatial and visuo-constructive disturbances. He had neither parkinsonism nor recurrent visual hallucinations t yp ica lly w e ll fo rm e d a n d d e t a ille d . Ne u ro im a g in g (co m p u t e d t o m o g ra p h y a n d m a g n e t ic re so n a n ce sp ectroscop y) show ed m ild d iffuse cortical atrop hy, m ostly on the left tem p oral lob e and a d ecrease of N-acetil-asp artate levels. A cholinesterase inhib itor w as p rescrib ed to this p atient d uring 6 m onths w ith clinically relevant b ehavioral effect. Diag nosis confirm ation w as m ad e b y p ost-m ortem neurop atholog ical find ing s. Macroscop ical features w ere m ild atrop hy on the frontal, p arietal and tem p oral lob es, noted ly on the frontal lob es. Microscop ically, there w as neuronal loss and d iffuse classic Lew y b od ies. Brainstem (sub stantia nig ra, rap he nucleus, locus coeruleus, p ed unculop ontine nucleus), lim b ic cortex, and neocortex (frontal, p arietal and tem p oral) w ere the areas of p red ilection for Lew y b od ies. Hem atoxylin-eosin and Bielschow sky staining d id not show neuronal sw elling (b alooned cell), arg yrop hilic inclusion (Pick’s b od ies), neurofib rillary tang les nor senile p laq ues. Im m unohistochem ical staining for anti-tau, anti-β-am yloid , and anti-p rion p rotein w ere neg ative. Antiub iq uitine reaction w as p ositive for Lew y b od y in the cereb ral cortex and b rainstem .
KEY WORDS: nig htm ares, extrap yram id al sig ns, visual hallucination, d em entia, w ith Lew y b od ies d em entia.
Pesadelos sem atonia como primeiro sintoma da doença difusa a corpos de Lew y
RESUMO - É d escrito o caso d e hom em d e 70 anos d e id ad e com história p rog ressiva, iniciad a há 6 anos com pesadelos, problem as com a atenção e m em ória recente, dificuldade de encontrar lugares fam iliares e episódios d e alucinação visual p ouco elab orad os. Na p rim eira avaliação neurop sicológ ica havia d éficit d ifuso d e leve intensid ad e, esp ecialm ente nas funções d e atenção e m em ória, viso-esp acial e viso-construtiva. Não houve sinais de parkinsonism o nem delírios recorrentes. Tom ografia cerebral com putadorizada m ostrou atrofia cerebral p róp ria d a id ad e. Ressonância m ag nética com esp ectroscop ia foi norm al p ara faixa etária, em b ora houvesse red ução na curva d o N-acetil-asp artato. O uso d e um inib id or colinesterásico d urante 6 m eses m elhorou sua autonom ia cog nitiva, com p ortam ento e sono. Os achad os d e necróp sia evid enciaram atrofia cortical nas regiões fronto-p arieto-tem p orais com m aior acentuação nos lob os frontais. Do p onto d e vista histop atológico, havia m od erad a q uantid ad e d e corp os d e Lew y intracitop lam áticos d istrib uíd os em tod o o córtex cereb ral, a lém d e d esp o vo a m en t o n eu ro n a l co m lib era çã o p ig m en t a r. As co lo ra çõ es p o r h em a t o xilin a -eo sin a e Bielschow sky não revelaram células b aloniform es, corp os d e Pick, d eg eneração neurofib rilar e p laca senil. Com exceção d os corp os d e Lew y intracitop lasm áticos, as reações im uno-histoq uim icas foram neg ativas p ara anti-ub iq uitina, anti-tau, anti-β am ilóid e, e p roteína anti-p rion.
PALAVRAS-CHAVE: p esad elos, sinais extrap iram id ais, alucinação visual, d em ência, d em ência a corp os d e Lewy.
1Behavioral Neurology Unit, Departm ent of Neurology, Faculty of Medical Sciences, University of Pernam buco, Recife PE, Brazil; 2Departm ent
o f Pat h o lo g y, Healt h Scien ces Cen t er, Fed eral Un iversit y o f Pern am b u co , Recife PE, Brazil. Received 13 Jan u ary 2003, received in fin al fo rm 6 Ju n e 2003. Accep t ed 3 Ju ly 2003.
Dr. Paulo Robert o de Brit o-M arques - Rua Sport Clube do Receif e 280/616 - 50070-450 Recif e PE - Brasil. E-mail: pbrit o@t ruenet .com.br
Dem en t ia w it h Lew y b o d ies (DLB) is a co m m o n fo rm o f d em en t ia in t h e eld erly. It acco u n t s fo r 15-20% o f cases o f d em en t ia in o ld ag e. Lew y b o d ies are intracytop lasm ic, sp herical, eosinop hilic neuronal in clu sio n b o d ies1. Lew y b o d y fo rm at io n is cen t ral t o
t h e p a t h o lo g ica l p h e n o t yp e o f a sp e ct ru m o f d iso rd ers2 as at axia t elan g iect asia3, co rt ico b asal d
e-g en eratio n4, Dow n’s synd rom e5, fam ilial early-o n set
Alzh eim er’s d isease (AD)6, Hallervo rd en -Sp at z d
ise-ase7, m o t o r n eu ro n d isease8, m u lt ip le syst em at ro
-p hy9, neuroaxonal d ystrop hy10, p rog ressive sup
ranu-clear p alsy11, su b acu t e sclero sin g p an en cep h alit is12.
d isease (PD)2. Stud ies of d em entia in the eld erly sug
-g est t h at an o t h er d iso rd er o f Lew y b o d y p at h o lo -g y is eq u ally o r even m o re co m m o n t h an PD. Th is syn -d ro m e o f DLB h as b een n am e-d several -d iag n o st ic lab els and is characterized b y d em entia, m ild p arkin-sonism , visual hallucinations, and fluctuations of the consciousness. Althoug h m any of these features can b e in PD, t h e p at ien t s w it h DLB t en d t o h ave early n eu ro p sych ia t ric fea t u res w h ich ch a ra ct erize t h e clin ical p ictu re, b ein g th e d iag n o sis o f th e syn d ro m e in p ract ice is co n cern ed w it h t h e d ifferen t ial d iag -nosis of AD. The d ifferential d iag -nosis of DLB d isease h a s received in crea sin g a t t en t io n in t h e p a st few years in view o f it s p o t en t ial t h erap eu t ic im p lica-t io n s1,2. Fo r in st an ce, n ig h t m are t h at h as n o t b een
in clu d ed in co n sen su s crit eria fo r t h e clin ical d iag -n o sis o f p ro b ab le a-n d p o ssib le d em e-n t ia w it h Lew y b o d ies as a sp ecific sym p t o m1,13.
Th e rep o rt o f t h is case is u n iq u e b ecau se n ig h t -m are w as th e first sy-m p to -m fo u n d an d it kep t g o in g t h ro u g h all t h e co u rse o f t h e d isease, excep t d u rin g six m onths when the patient was treated with a choli-n est erase icholi-n h ib it o r, rivast ig m icholi-n e.
M ETHOD
A d iag nosis of p ossib le Lew y b od ies d em entia w as m a-d e in a m ale p at ien t acco ra-d in g t o t h e crit eria a-d escrib ea-d b y McKeit h et a l.1. Th e Clin ical Dem en t ia Rat in g (CDR)14 an d Glo b al Det erio rat io n Scale (GDS)15 m et h o d s w ere u sed . Neu ro p sych o lo g ical assessm en t w as m ad e o n t h e b asis o f so m e it e m s o f Alzh e im e r’s Dise a se Asse ssm e n t Sca le (ADAS)16 an d Min i-Men t al St at e Exam in at io n (MMSE)17. Th e Carreg iver Bu rd en w as u sed fo r m easu rin g careg iver st ress18. Th e p at ien t w as also su b m it t ed t o n eu ro im ag in g st u d ies su ch as co m p u t ed t o m o g rap h y (CT) an d sp ect ro sco p y m ag n et ic reso n an ce im ag e (SMRI). Th e n eu ro p h at o lo g ical exam in at io n w as p erfo rm ed acco rd in g t o Co n sen -su s g u id elin es fo r t h e clin ical an d p at h o lo g ic d iag n o sis o f d em en t ia w it h Lew y b o d ies1. Th e en t ire b rain w as fixed 10% fo rm alin fo r 4 w eeks p rio r cu t t in g an d it w as cu t in t o co ro n a l se ct io n s. We e xa m in e d 6 m m t h ick p a ra ffin em b ed d ed sect io n s fro m t h e m id d le fro n t al, u p p er t em -p o ral, m id d le t em -p o ral, in ferio r -p ariet al lo b es, b ilat erally, h yp p o cam p u s g yri, am yg d alo id n u clei, an d m esen cep h lon. They were routinely p rocessed and stained with hem at o xilin eo sin , an d Bielsch o w sky m eat h o d s. Im m u n o h ysat o -chem ical reactions with antib od ies ag ainst tau, ub iq uitine, β-am ylo id w ere carried o u t .
CASE
A 70-year-old m an right-handed, retired, without schooling, was adm itted in Oswaldo Cruz University Hospital Pernam buco-Brazil, in January 1995. He be-gan exhibiting excessive m ovem ent associated with
nightm ares with no atonia (NWNA) about 6 years pri-or to his first evaluation. One year befpri-ore the first con-sult, the patient had an intestinal infection and he started to have visospatial disorder, some memory pro-blem s and attention deficits. During all course of the disease he had incapacity to find his way around the neighbourhood and other form erly fam iliar environ-ments, mild visual hallucinations and jealousy episodes with m ild to m oderate fluctuation in cognitive func-tions including situafunc-tions of going blank.
Du rin g h is NWNA h e b eg an exh ib itin g a b eh avio r su ch a s ju m p in g o u t o f t h e b e d , sh o u t in g , a n d scream in g . He w as t alkat ived as if t alkin g t o im ag i-n ary p eo p le ai-n d p resei-n t ed m ai-n y m o vem ei-n t s as a fig h t . So m et im es h e fell fro m t h e b ed o n t h e flo o r o r g o t u p fro m b ed t o fig h t w it h t h e w all. Th e p a-t ien a-t ´ s w ife u sed a-t o w ake h im u p an d ask h im w h aa-t h ad h ap p en ed . He w h en ro u sed fro m sleep u sed t o t ell h er h is n ig h t m ares an d h e w o u ld so o n fall b ack asleep ag ain . In it ially, t h ese ep iso d ies o ccu rred o n ce o r t w ice p er m o n t h , an d t h ereaft er t h eir freq u en cy g ra d u a lly in crea sed . Excessive d a yt im e sleep in ess w ith ep isod es of confusion d uring w akefulness w ere p resen t ed an d it w as accen t u at ed b y a n o n st im u la-t in g en viro n m en la-t . Perso n al an d so cial fu n cla-t io n s an d p erfo rm an ce in d aily livin g skills w ere m arked ly im -p aired in the early stag es. The -p attern of his m em ory im p airm en t m an ifest ed it self as so m e d ifficu lt y in tasks w ith attentional req uests. Mem ory of everyd ay life seem ed t o b e im p airm ed . He h esit at ed ab o u t w here he left som e ob jects and ord inary d aily events w ere n o t rem em b ered , b u t so m e o f h is d aily livin g activities were not im pairm ed. There were fluctuation in co n fu sio n an d t em p o ral d eso rien t at io n ep iso d ies d u rin g all co u rse o f t h e d isease, b u t t h e p erio d icit y an d m ag n it u d e o f t h ese even t s w ere variab le. He w as a p reviously efficient and ind ep end ent truck d ri-ver. He n ever h ad an y d ifficu lt ies t o d rive an yw h ere as he always p reviously d rived his truck all over Brazil. Ho w ever, h e w as u n ab le t o fin d h is w ay aro u n d t h e n eig h b o u rh o o d a n d o t h er fo rm erly fa m ilia r en vi-ro n m en t s. He h ad a feelin g h e w as st ep p in g o n an u n even su rface. He h ad jealo u sy fro m h is w ife w it h an y m an . So m et im es h e d id n o t w an t h is w ife t o leave t h eir h o m e t o sh o p o r o t h er t rivial t h in g s.
vascu lar risk fact o rs. He d id n o t u se m ed icat io n s as b et a b lo ckers o r L-d o p a o r n eu ro lep t ics d u rin g all d isease co u rse. His fam ily h ist o ry d isclo sed n o d e-m en t in g d iseases an d n o p sych iat ric ab n o re-m alit ies em erg ed fro m h is m ed ical h ist o ry.
Th e fin d in g s o f t h e n eu ro lo g ical exam in at io n 6 years aft er t h e o n set o f sym p t o m s revealed a rig h t -hand ed , attentive to the exam , coop erative and sen-sit ive m an . Th ere w ere n o t p yram id al, ext rap yram i-d al, o r cereb ellar sig n s. No p erip h eral n eu ro p at h y w as fo u n d , an d o cu lar m o vem en t w as n o rm al. He kn ew h o w t o h an d le m o n ey very w ell, h e co u ld o n ly w rit e h is n am e an d m ake sim p le arit h m et ical o p era-t io n s. He w as fu lly o rien era-t ed in era-t im e an d sp ace an d h e h ad co llab o rat ed ad eq u at ely d u rin g t h e t est ses-sio n s. He o b t ain ed a sco re o f 0,5 o n t h e CDR16 an d
19/30 o n t h e MMSE17. Th e p at ien t u sed 1,5 m g b .i.d
(3m g/day) throught 6m g b.i.d (12m g/day) of rivastig-m in e d u rin g six rivastig-m o n t h s (Tab le 1).
Bio ch em ical ro u t in e, h em at o lo g ical an d so ro lo -g ical in vest i-g at io n s w ere n o rm al. Po lyso n o -g rap h ia evalu at io n w as n o t d o n e in t h is p at ien t t o co n firm t h e clin ical h yp o t h esis o f b eh avio ral rap id eyem o -vim en t (REM) d iso rd er. A CT o b t ain ed w h en h e w as 69 years o ld sh o w ed m ild d iffu se co rt ical at ro p h y, sp ecially o n t h e left t em p o ral lo b e. SMRI p erfo rm ed w h en h e w as 76 years o ld revealed d iffu se co rt ical at ro p h y, m ain ly o n t h e t em p o ral lo b es, b ein g t h e left m o re at ro p h yc t h an t h e rig h t . Th e h ip p o cam p i g yri w ere n o rm al, sp ecially w h en t h ey w ere co m p a-red w it h t h e t em p o ral lo b es (Fig 1).
Wh en t h e p at ien t d isco n t in u ed rivast ig m in e, h e g o t a p ro g ressive w o rsen in g o f t h e d em en t ia, an d ab out eighteen m onths after, he had a sub acute sub -d u ral h em at o m a w h en h e fell fro m h is b e-d , -d u rin g a n ig h t m are. He u n d erw en t a n eu ro su rg ery an d re-m ain ed b ed rid d en an d all h is p erso n al n eed s w ere
cared fo r b y n u rsin g p erso n al at t h e Osw ald o Cru z Un iversit y Ho sp it al. He d ied at t h e ag e o f 77, aft er a total clinical course of 12 years, from the first NWNA o n , an d 6 years fro m t h e first co n su lt . His d eat h o n May 2nd 2001 w as at t rib u t ed t o an in fect io n . Th e
clin ical d iag n o sis w as t h at o f a p o ssib le d em en t ia w it h Lew y´ s b o d ies.
Gro ss p at h o lo g y. Th e p o st m o rt em in t erval w as 14 hours. The b rain w eig hed 1100 g ram s. The lep to-m en in g es an d cereb ral art eries w ere n o rto-m al. Th ere was m ild cortical atrop hy on the frontal, p arietal and t em p o ral lo b es, sp ecially o n t h e fro n t al lo b es. Co ro -n al sectio -n s revealed m o d erate d ilatatio -n o f th e m e-dium ventricules. Midbrain sections showed m ild pal-lor in the sub stantia nigra. There were no other gross ab n o rm alit ies.
Table 1. Clinical and Neuropsychological assessement w it h rivast igmine
Oct ./98 Jan ./99 Ap r./99
Do m a in Test s Sco re Sco re Sco re
Lan g u ag e16 Oral n am in g 2/12 2/12 2/12
Visu o sp at ial16 Dig it sym b o l Rig h t 0 Rig h t 1 Rig h t 0
Wro n g 1 Wro n g 2 Wro n g 1 Om issio n 0 Om issio n 3 Om issio n 1
Gn o sia16 Fin g er g n o sia 4/5 2/5 2/5
Carreg iver Bu rd en18 Overlo ad 3,2,3,4 1,1,1,1 1,1,1,1
Eco n o m ic t rain s 3,3,2 3,3,2 3,3,2
Ro le cap it ivit y 1,1,1 1,1,1 1,1,1
Screen in g17 Min i Men t al St at e Exam in at io n 17/30 22/30 19/30
Scale15 Glo b al Det erio rat io n Scale 5/7 4/7 3/7
Micro sco p ic p a t h o lo g y. Bra in se ct io n s w e re st ain ed w it h h em at o xylin an d eo sin , Bielsch o w sky, an d im m u n o cyt o ch em ically fo r an t iu b iq u it in e, an t i-t a u a n d a n i-t i-β-a m ylo id p ro t e in . Exa m in a t io n o f m id d le fro n t al g yru s, su p erio r an d m id d le t em p o ral, inferior p arietal gyri, hyp p ocam p i, am ygd aloid nuclei a n d m e se ce p h a lo n se ct io n s re ve a le d m o d e ra t e am o u n t o f in t racit o p lasm ic Lew y b o d ies an d n eu ro n al lo ss. Exam in at io n o f t h e p ed u n cu lo p o n t in e n u -clei, locus coeruleus, b asal nucleus of Meynert, rap he d orsal nuclei, and sub stantia nig ra show ed Lew y b o-dies and also neuronal loss (Fig 2). Hem atoxylin-eosin (HE) and silver stains d id not show neuronal sw elling (b alo o n ed cell o r Pick’s cells), arg yro p h ilic in clu sio n (Pick’s b o d ies), n eu ro fib rilla ry t a n g les, a n d sen ile p laq u es. Im m u n o h ist o ch em ical st ain in g fo r an t ib o -dies against tau, and β-am yloid were tested negative. Th ere w ere also im p o rt an t release o f lip o fu scin an d an o xia sig n s in t h e g reat p yram id al n eu ro n s. No fo cal w h ite m atter lesio n s o r vascu lar d isease w ere o b -served . Defin it ive d iag n o st ic w as d iffu se Lew y b o d y d isease.
DISCUSSION
This case was based on the supposition that NWNA was a specific sym ptom for the clinical diagnosis of p rob ab le and p ossib le d iffuse Lewy b od ies d isease (DLBD). The antem ortem features used in classifying
such patients with dem enting illnesses have not in-cluded phenom ena reflecting brainstem alterations, that m ay occur several years before the developm ent of neurodegenerative signs. The patient´ s wife related m e that following m ore than 6-year history suggestive of NWNA, the clinical features shifted to progressive cognitive deficit with m ild spontaneous visual halluci-nations, and notedly progressive fluctuation in cogni-tion. He did not have parkinsonism . According to Bar-raquer y Bordas19, the practice of polisonographic
re-cordings allows to identify loss of m uscle atonia, as well as the m otor com plex activities that identify the im paired subject, while the bioelectrical desyncroniza-tion and R.E.M persist. On the other hand, a careful m edical interview with the affected subjects with that syndrom e m ade possible to recognize the correspon-dence, the link, between the dream content, usually full of angst, fear, and also agressivity, and the behavior, m ostly destructive of the subject in contem porary pa-rasom nia: socks, kicks, strangling and fleeing etc, as observed in this case.
Rivast ig m in e w as u sed as t reat m en t fo r t h is d ise-ase w it h g o o d clin ical resp o n se. Po st -m o rt em exm ination of the liexm b ic cortex, neocortex (frontal, p a-riet al an d t em p o ral) an d m id b rain (lo cu s co eru leu s an d su b st an t ia n ig ra) an d b rain st em (rap h e, p ed u n -culop ontine and Meynert nuclei) showed loss of neu-ro n s an d t h e p resen ce o f Lew y b o d ies. Th ese clin ical
an d p at h o lo g ic ch an g es w ere also fo u n d in t h e five cases p u b lish ed o f REM sleep b eh avio r d iso rd er20-23.
Th e Seco n d In t ern at io n al Wo rksh o p o n DLB reco m -m en d ed t h at t h e Co n sen su s crit eria sh o u ld co n t n u e t o b e u sed in it s cu rren t fo rm at , t h e o n ly m o d i-ficat io n b ein g t h e ad d it io n o f REM sleep b eh avio r d iso rd er an d d ep ressio n t o t h e list o f ad d it io n al fea-t u res “su p p o rfea-t ive” o f fea-t h is d iag n o sis13. Po ssib ly th ere
is a clin ical an d p at h o lo g ical relat io n b et w een t h e NWNA sym p t o m an d t h e DLBD. Ad d it io n al clin ical features of DLBD, NWNA as specific clinical sym ptom , m ay im p ro ve t h e p rem o rt em d iag n o st ic sen sit ivit y, sp ecificity, and p red ictive value of p ub lished criteria.
The p hysiologic m echanism s governing non-rap id eye m ovem ent (NREM) and REM sleep lie in the p on-t in e reon-t icu lar fo rm aon-t io n , as p aron-t s o f on-t h e ascen d in g ret icu lar act ivat in g syst em . Ch o lin erg ic an d am in er-gics neurons interact with the p ed unculop ontine nu-clei an d th e m ed ial p o n tin e reticu lar fo rm atio n (d o r-sal n u cleu s o f rap h e). Th erefo re, lesio n s o f th e rap h e n u clei, su b st an t ia n ig ra an d m ain ly lo cu s co eru leu s d ecrease o f m o n o am in e levels an d in crease th e REM act ivit y b y in h ib it in g ch o lin erg ic n eu ro n s in t h e p e-d u n cu lo p o n t in e n u cleu s m ee-d ia t in g a t o n ia e-d u rin g REM sleep20,24. Ea rly a ccu ra t e clin ica l d ia g n o sis o f
DLBD is p art icu larly im p o rt an t t o m an ag e issu e su ch as avo id in g severe n eu ro lep t ic sen sit ivit y react io n s, a ch ie vin g t h e o p t im a l le ve l o f a n t ip a rkin so n ia n t rea t m en t w it h o u t exa cerb a t in g p sych ia t ric sym -p t o m s, an d a -p o ssib le b en eficial res-p o n se t o ch o li-n est erase ili-n h ib it o rs25. Th erefo re, ad d it io n al clin ical
feat u res o f DLBD m ay im p ro ve t h e p rem o rb id d ia-g n o st ic sen sit ivit y, sp ecifivit y, an d p red ict ive valu e o f p u b lish ed crit eria as t h is case.
Th e au t o p sy sh o w ed co rt ical Lew y b o d ies t h at w ere less w ell circu m scrib ed an d d ifficu lt t o reco g -nize using conventional staining m ethods, but readily visualized with antiubiquitine im m unocytochem ical detection. The areas of prediletion for Lewy bodies on the coronal slices through human brain depicting Brodm ann areas were frontal (Brodm iddle frontal giry 8/9), teBrodm -poral (superior tem -poral giry 22), tem -poral (m iddle tem poral gyri 21), parietal (inferior parietal lobule 40), h ip p o ca m p y g yri, a m yg d a lo id n u cle i, a n d lo cu s coeruleus26. Besides these Brodm ann areas there were
also Lewy bodies in Meynert, raphe, locus coeruleus and pedunculopontine group nuclei in our case.
Many deficits in cholinergic neurotransm ission are seen in patient brains with Lewy body dem entia. They are p ro b ab ly seco n d ary t o p resyn ap t ic d ep let io n in b ra in st em a n d b a sa l fo reb ra in ch o lin erg ic n u clei, w ith m ore p reservation of p ostsynap tic m echanism s
t h an seen in AD26. Th erefo re, d ru g s en h an cin g cen
-tral cholinerg ic function rep resent a rationally-b ased t h erap eu t ic ap p ro ach t o t h is d iso rd er26. Carb aco l o r
g lu t am at em ed iat ed excit at io n o f ch o lin erg ic n eu -ro n s in t h e p ed u n cu lo p o n t in e n u cleu s in d u ces REM sleep , an d acet ylch o lin est erase in h ib it o rs d ecrease REM sleep latency and increase REM sleep d uration20.
It is p o ssib le t h at t h is p at ien t h ad a sig n ifican t n eu -rob ehavioral im p rovem ent with rivastigm ine, and his clin ical im p ro vem en t m ig h t b e relat ed t o a ch o lin er-g ic in t eract io n b et w een t h e lo cu s co eru leu s an d t h e rap h e n u clei, an d t h e p ed u n cu lo p o n t in e n u clei24.
Neu ro p sych o lo g ic t est s reveal d eficit p ro file o f d eficits that help to id entify DLBD27. Visuosp atial d
is-turbances were the m ost found frequently sym ptom s in o u r p at ien t b o t h in relat io n t o t h e m ed ical rep o rt and the ob jective clinical assessem ents. It was shown t h at t h ese erro r t yp es w ere a m an ifest at io n o f visu -o sp at ial d eficit , revealin g a m aj-o r p r-o b lem -o f t h e DLBD: t h e sp at ial o rg an izat io n . Th ere w ere n o t im -p o rt a n t sig n ifica n t ch a n g es in t h e la n g u a g e t est s w h ile t h e n eu ro p sych o lo g ical t est s w ere im p ro ved o n t h e MMSE17, GDS15, Careg iver Bu rd en18. Th is p
a-t ien a-t also p resen a-t ed even g reaa-t er im p ro vem en a-t o f t h e n ig h t m ares, p erso n al an d so cial fu n ct io n an d d aily livin g skills p erfo rm an ce an d in o t h er co g n it ive and neuropsychiatric sym ptom s as well, when he was treated w ith a ch o lin estearase in h ib ito r. Ap p ro xim at ely 10% o f at h e DLB p o p u laat io n ap p ear at o b e h o m o -zyg o u s t o t h e b u t yrylch o list erase K lo cu s co m p ared t o o n ly 1 o r 2% in t h e AD g ro u p , so t h at t h is g en et ic risk fact o r seem s t o d ist in g u ish t h e t w o d iseases2.
Th is fin d in g m ay b e relevan t t o t h e h yp o t esis t h at DLB cases are m o re likely t o resp o n d t o ch o lin erg ic t h erap y t h an AD2. Wh en t h e p at ien t d isco n t in u ed
rivast ig m in e, h e g o t a p ro g ressive w o rsen in g o f t h e d em en t ia. Deficit s in m em o ry, lan g u ag e, an d o t h er co g n it ive skills o verlap w it h t h o se seen in a severe p rim ary d em entia, b y a com b ination of cognitive and neurolog ic d isab ility. During a nig htm are the p atient had craniocereb ral traum a and had a sub acute sub -d u ral h em at o m a. He u n -d erw en t a su rg ery an -d re-m ain ed b ed rid d en an d all h is p erso n al n eed s w ere cared fo r b y t h e n u rsin g p erso n al at t h e Osw ald o Cru z Un iversit y Ho sp it al.
-w een t h e DLBD versu s o t h er b rain p at h o lo g ies, (iv) rivastig m ine, a cholinesterase inhib itor, m ay b e used as a t h erap eu t ic ap p ro ach in p at ien t s w it h p o ssib le DLBD, (v) t h e p resen ce o f Lew y b o d ies in t h e lo cu s co eru leu s, su b st an t ia n ig ra, rap h e n u cleu s an d sp e-cia lly in t h e p e d u n cu lo p o n t in e n u cle u s m a y b e in vo lved w it h t h e o f NWNA m ech a n ism , (vi) t h e occurrence of Lewy bodies in the neocortex and basal n u cleu s o f Meyn ert m ay p lay an im p o rt an t ro le in t h e p at h o g en esis o f co g n it ive an d m em o ry d ist u r-b an ces, resp ect ively, an d (vii) t h e d iffu se Lew y r-b o d y d isease is a n o so lo g ic en t it y. Fu t u re d evelo p m en t s in clinical classification of the d em entias should take t h ese co n sid erat io n s o n acco u n t .
Acknow ledgment - The authors acknowled ge the con-t rib u con-t io n o f con-t h e p acon-t ien con-t an d h is fam ily fo r con-t h is arcon-t icle. Th e authors thank Ana Paula De Biase Mulatinho, occup ational t h e ra p ist a t Be h a vio ra l Ne u ro lo g y Un it - Re se a rch o n Alzh eim er´ s Disease an d Relat ed Diso rd er.
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