www.thelancet.

com vo| ]8u 2u de octubre de 2ui2 i2

TheLancet
Publicado
2ui2, ]8u: i2 | u
Ln|| nea
13deabril de2012
htttp://DX.Doi.org/10.1016/
S0140-6736(11) 61304-4
sco|oq|a fso||qca,
unversdad de 8e|efe|d,
8e|efe|d, A|emana
(Prof. H J Markowitsch PhD,
Un MD Staniloiu)
lnsttuto de estudos avan|ados,
, A|fred krupp
urefswa|d, A|emana
(H J Markowitsch), Centre for
Addcton and Menta| uea|th,
1oronto, ON, Canad|
(Un Staniloiu), y |a unversdad
de 1oronto, ON, Canad|
(Un Staniloiu)
Correspondencia con:
Prof. Hans J Markowitsch,
Psicolog a fisiol gica,
Universidad de Bielefeld,
Postfach 10 01 31,
33501 Bielefeld, Alemania
h[mar|owtsch@uNl-8e|efe|d.de
1rastornos amn| scos
Hans J Markowitsch, Angelica Staniloiu
Disturbios de la memoria con frecuencia ocurren despu s de da o cerebral, pero pueden estar asociados con
enfermedades psiqui tricas, as . Amnesia la forma m s severa de la debilitaci n de la memoria tiene varias
variantes, incluyendo anter grada y amnesia retr grada, material-specic y speci -modalidad c amnesia y la
amnesia global transitoria. B squedas en bases de datos para obtener un Resumen de la investigaci n de la amnesia
de los ltimos 5 a os. Investigaci n en amnesia ha aumentado exponencialmente, probablemente debido a la
disponibilidad de modernas t cnicas de im genes cerebrales. En consonancia con la opini n de que no es una
unidad de memoria pero se organiza en varios sistemas, amnesia es descrita como una enfermedad polifac tica con
un pron stico pobre con frecuencia.
lntroducc|n
La annosia dol tinino so utiliza iincialnonto on dos
loinas. En iinoi lugai, so utiliza gonoialnonto aia dosciilii
cualquioi cit dotoiioiai-cin o cativo sovoia do la nonoiia,
indoondiontononto do la causa. En sogundo lugai, so utiliza
on lnoa con la visin tiadicional quo la annosia os un
dotoiioio do la nonoiia quo so ioduco on ausoncia do otios
tiastoinos cognitivos sulstancialos y so linita a tiastoinos c
soci. Estos tiastoinos conocido cono tiastoinos
annsicos o annsicos sogn diNnUMLZF
intoinacional tionon cono caiactoistica iincial una
dolilitacin do la nonoiia quo no os dolido a la dononcia o
doliiio y ioiosonta una disninucin do un nivol luncional
logiado iovianonto. Esto iochazailos on la luncin di
oiontiatos do inlantil annosia o nouio - tiastoinos dol
dosaiiollo.
En osta iovisin, nos dosciilon la classicacin do
sistonas do nonoiia y iosunii los asoctos iolovantos do lo
quo iovoca tiastoinos annsicos, la nouioliologa,
oidoniologa, diag nosis y gostin. Discutinos la
nouioinagon y los ostudios gonticos y hacoi hincai on la
nocosidad do iigoi notodolgico con iosocto a la iuola do
nonoiia aiadignas.
Sstemas de |a memora y |os procesos de memora
Aunquo la annosia dol tinino so utiliz lastanto
liliononto hasta la dcada do 1980 a nonudo aia
dosciilii la idida total do la nonoiia ahoia
1
Salonos quo la nonoiia dotoiioio on los tiastoinos
annsicos os iolallo quo soa iostiingido a las clasos c
socido nonoiia. Esta visin os aoyada oi la
oxistoncia do vaiios sistonas do nonoiia distintos, cada
uno con di Z8 3 4 ]
Adons do la divisin on la nonoiia a coito y a laigo
lazo, solio todo, condujo ol tialajo do Tulving,
2 4
a un catin do classilasado on ol contonido do la
nonoiia a laigo lazo on los sistonas Viow (guia,
quo son joiiquicanonto oiganizada sogn su suuosta
ontogontica y lilogontica dosaiiollan nont (andico.
So haco una distincin ontio nonoiia oisdica y
autoliogilica (EAM oi ojonlo, iocoidando la cona do la
nocho antoiioi y nonoiia autoliogilica sonntica (oi
ojonlo, la nonoiia o conocinionto do su locha do
nacinionto. Monoiia autoliogilica Sonan-tic uodo soi
dotoiioiado on annosia disociativa, oio gonoialnonto so
consoiva on otios tiastoinos annsicos, conocoi un hocho so
suono quo nocositan nonos inloinacin contoxtual y
asociativa quo iocuoi-loi un ovonto oisonal.
La incaacidad aia alnaconai inloinacin nuova a laigo
lazo so dononina annosia antoigiada y la incaacidad
aia iocoidai la inloinacin alnaconada so dononina
annosia iotigiada. Monoiia do iotio-giado dotoiioio
siguo gonoialnonto la loy do Rilot do iogiosin os docii,
iocuoidos iociontos son ns ojada a .
5
los antoiioios. Annosia iotigiada aislada os divulgada
aia ocuiiii dosus do incidontos nouiolgicos o
sicolgicos. Algunos invostigadoios sostionon quo incluso
con claia ovidoncia do canlios atolgicos on ol coiolio,
lactoios sicolgicos sustancialnonto contiiluyon a
oisistoncia do dolilitacin EAM iotio-giado.
6
EAM siivo lunc-cionos iosoctivos y iotiosoctivos. La
caacidad do iocoidai hacoi una accin lutuia on
iosuosta a un iosocicuo od (nonoiia iosoctiva
odia ostai dotoiioiado on tiastoinos annsicos cono
consocuoncia do altoiacionos on las luncionos ojocutivas,
nonoiia sonntica o EAM.
/
Piocosanionto do nonoiia os inlcito (sulconscionto o
oxlcita (conscionto. Piocosanionto inlcito os
ticanonto junto con iocodiniontos y sistonas do colado
do la nonoiia y iocuoido oxlcito so asocia gonoialnonto a
oico-tual y nonoiia sonntica y EAM. EAM os
doondionto dol ostado, una tina iocuoiacin do
iocuoidos so ioduco cuando las condicionos anliontalos y
ostado do nino coincidon con los quo ostalan iosontos
cuando la nonoiia luo codilicada. Panol 1 nuostia vaiios
tios do annosia (vaso ol andico do los iocosos
sicolgicos asociados con la nonoiia.
Neuroanatom| a y Neurobo|oq| a de |a memora e|
debate acerca de s e| cerebro contene reqones
funcona|mente especa||adas o actos uesta|t-como
(como un todo) tomaron
1
una nuova dinonsin con la llogada do luncional
Crteros de estrateqa y se|ecc| n de b s|ueda
Esta revisi n se basa en material identi ed a trav s de
b squedas en PubMed, Medline y Scopus de investigaci n
original o
Ver
revisi n de art culos desde 2005 a principios de 2011
escrito en ingl s, alem n y franc s, con una
combinaci n de las palabras "amnesia", "memoria",
"deterioro de la memoria", "disturbios de la memoria",
"gen tica" y "tratamiento". Basamos la selecci n del
material en su calidad, originalidad y relevancia para el tema.
Tambi n hemos citado algunos cap tulos de libro y
art culos m s antiguos seminales sobre el tema.
Ln|| nea Apndice
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M l i l i z er P D F T ra nsl a o r F ree v ersi o n - ra nsl a i o n i s l i m i ed o ~ 3 p a g es p er ra nsl a i o n.
M l i l i z er P D F T ra nsl a o r F ree v ersi o n - ra nsl a i o n i s l i m i ed o ~ 3 p a g es p er ra nsl a i o n.
i]u www.thelancet.com vo| ]8u2udeoctubrede2ui2
proy ecci n de imagen, que a v eces apunta hacia un alto
grado de especializ aci n cortical. Amnesias se presentan
despu s del da o a
8
las estructuras del cuello de botella a trav s del cual la
informaci n tiene que pasar antes de se almacena a largo
plaz o, pero tambi n puede tomar lugar
9
despu s del da o cortical generaliz ada (panel 2; v ase el
ap ndice para un esquema de los dos circuitos principales implicados
en el enlace de memoria yalmacenamiento a largo plaz o). Panel 3
presenta las regiones del cerebro cuy o da o (bilateral) es m s
frecuentemente implicado en amnesia.
Algunos trastornos amn sicos ocurren sin la ev idencia del gran
da o al cerebro en proy ecci n de imagen estructural
conv encional. Estos trastornos incluy en aquellas que son
aetio-l gicamente v inculada a mecanismos psicosociales, como
amnesias disociativ as o psic genas o s ndrome del bloque
mnestic ytrastornos amn sicos con un desconocido
10
causa(amnesiasfuncionales;v erpanel1).Despu sdela
inv estigaci n11
por HJM ysus colegas, se inform , v arios estudios 11
identi ed cambios en el cerebro la funci n a1 ejo regiones
con papeles cruciales en la memoria de procesamiento en los trastornos
amn sicos que no muestran ev idencia de da o cerebral estructural.
Losinv estigadoreshananaliz adolosdatosobtenidos
10,12,13
con glucosa PET de 14 pacientes en reposo con amnesia disociativ a y
sev eras deficiencias EAM retr gradas ydiv ulgado hipometabolismo
en las regiones temporofrontal correcto, especialmente en la cortez a
prefrontal inferolateral.
10
Procesamiento en v arios sistemas de memoria se asocia
con mecanismos similares ypasos moleculares a trav s
muchasespecies,especialmentedurantelacodificaci n,laconsolidaci n,
yalmacenamiento. Varios tipos de plasticidad sin ptica fav orecen
la formaci n de la memoria, como la potenciaci n a largo plaz o y
depresi n, sinaptog nesis yremodelaci n sin ptica. Los
mecanismos celulares ymoleculares bajo mentira larga-
adquisici n de memoria plaz o consisten en diferentes v as de
se aliz aci n, transcripci n gen tica, la s ntesis de
prote nas ycambios morfol gicos sin pticos.
Almacenamiento a largo plaz o de
14,15
recuerdos podr an necesitar activ os mecanismos
moleculares autosostenibles (por ejemplo, una prote na del
pri n funcional).
16
Ambientalmente impulsados cambios en la formaci n de la
memoria a largo plaz o yla plasticidad sin ptica pueden
surgir como resultado de cambios en la s ntesis de
prote na ytranscripci n g nica mediante mecanismos
epigen ticos (DNA metilaci n, cationes modi qu mica post
traslacional histona o micro RNAs).
rev ersible mediante manipulaci n farmacol gica.
16,17
Algunos cationes modi epigen tica pueden ser
17
Catones c|ass|lnternacona| de| cat| n de
trastornos amn| scos |a C|ass|estad| stca
nternacona| de enfermedades y prob|emas de sa|ud
conexos, d| cma revs| n (ClL-iu)
18
yla rev isi n del tex to de diagn stico yManual
estad stico de trastornos mentales, cuarta edici n
(DSM-IV-TR)
19
Codfcac| ny
conso|dac|n
A|macenamento de nformac| n
kecuperac| n
Memoraprocedmenta|
Mecnica o
habilidades relacionadas con el motor
Gangliosbasales,
reas relacionadas conel motor
Gangliosbasales,
reas relacionadas conel motor
Gangliosbasales,
reas relacionadas conel motor
Cebado
Una mayor probabilidad
de reconocer
previamente percibido
informaci n
Primaria y
cortezadeasociaci n
Primaria y
cortezadeasociaci n
Primaria y
cortezadeasociaci n
I
?
Memora perceptua|
El reconocimiento de
est mulos relacionados
alafamiliaridad
juicios
Posterior sensorial
corteza
Posterior sensorial
corteza
Posterior sensorial
corteza
Memorasem| ntca
H O = agua
2
a + b = c
2 2 2
Par s = capital de Francia
Orientada al presente
y representa hechos
generales libre de
contexto
Frontotemporal
corteza(izquierda)
Corteza cerebral,
estructuras del sistema l mbico
Corteza cerebral
(principalmente reas
de asociaci n)
Lps| dcas autoboqr| fcas
memora
La conjunci n de tiempo
subjetivo, autonoetic la
conciencia y la experiencia
del uno mismo
Frontotemporal
corteza(derecha), l mbica
regiones
Corteza cerebral
(principalmente reas de
asociaci n), regiones
l mbicas
Sistemal mbico,
corteza prefrontal
Sstemasde|amemoraa|arqop|a|o
Lstructurasre|evantesde| cerebro
Mi primera cita con Jane
El nacimientodeMarcel
Figuia:Lossstemasdememoraa|arqop|a|o|vewysusbasesdepresuntocerebro
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www.thelancet.com vo| ]8u 2u de octubre de 2ui2 i]i
clasilicai los tiastoinos annsicos solio la laso do su luoito
vnculo otiolgico con tiastoinos ndicos gonoialos, ol
diiocto
Panel 1:
o 1h /v oxt 5t
acionto quo oisisto ns all do la intoxicacin o
oiodo do iotiio o lactoios sicolgicos. Aunquo la
annosia disociativa, sicgono y luncional do tininos a
nonudo so utilizan indistintanonto, di h
oxiston ontio ollos (anol 1.
Vaiios tiastoinos ndicos uodon llovai a annsico
tiastoinos (giuo 2. En la nayoia do los casos, EAM os
oxclusiva o iodoninanto a ni 3 U
sustancia-dotoiioio do la nonoiia inducido ost onoigiondo
con linos toiauticos os docii, aia dolilitai a
iocuoidos tiaunticos oi olstaculizai su consolidacin o
iostallocinionto do iocuoiacin ost. Toiaia
oloctioconvulsiva
20
ha iocilido nucha atoncin con iosocto a la nagnitud y la
oisistoncia do la idida do la nonoiia iotigiada quo
uodo causai. Donosti la nayoia do las invostigacionos
con nodidas oljotivas
21
osa idida EAM on aciontos quo halan oxoiinontado
toiaia oloctio - convulsiva oia a coito lazo, oio on un
ostudio iosoctivo, natuialista y no aloatoiios, algunos
aciontos an tonan inodinontos EAM dosus do 6
nosos.
22
Da| o cerebra| de| sstema || mbco y |a amnesa de |a
amnesa provenen |os datos qrupo estudos e
nformes de| caso. Lstos estudos qrupo combnan con
frecuenca |os pacentes cuya amnesa tene d| |
dferentes causas, pero |ue probab|emente tenen e|
msmo |ocus prncpa| de da| o cerebra|. 1res formas
prncpa|es de amnesa han sdo c|| scamente
descrtas bas| ndose en e| |ocus de da| o cerebra|:
amnesa de| || bu|o tempora| meda| o de| hpocampo
(M1L), amnesa dencef| |ca y amnesa prosenc| fa|o
basa|. A pesar de a|qunas d| k|| || || u| || a| p| a| n|
comparten muchas caracter| stcas. varas partes de|
sstema || mbco pueden arreq|arse f| c|mente en
uesta|t-forma, |ue es apoyada por |cacones |ue
amnesa severa puede ser resu|tado de da| o cerebra|
en |a ntersecc| n entre e| M1L y e| denc| fa|o.
usando d| | | | | .| | | || || ||| | | || | | | | | | |d
apanco|aou y co|eqas proporcon|evdenca
23
oso dao lilatoial a lvoda ol aquoto do lio
ioyocta dosdo la loinacin dol hiocano (HF, aito dol
MTL a los cuoios nanilaios (aito dol dionclalo luo
sulyaconto a un caso do annosia sovoia.
El conlojo anigdalaios una iogin cuya contiilu-cin
a tiastoinos annsicos ha sido dolatida ost situado
dontio dol MTL y, conconitanto, os aito dol ciicuito
lnlico lasolatoial con conoxionos al dionclalo y
iosonclalo lasal. La angdala ost inlicada on ol
naicajo onocional do EAM. Activacin do
24
angdala doiocha so iogisti duianto la iocuoiacin do
viojo EAM onocional y Asociacin do caias con ono
convoncional
25
juicios (nonoiia social. Huilonann von iosoto 26
quo tanto nnosia hioiactivo y annosia oiionotional
15
(nonoiias do disninucin do ovontos noutios duianto la
codilicacin sinultnoanonto nojoiada do un ovonto
avoisivo doondon do angdala, vaiiando on luncin do la
ontiada noiadionigico-glucocoiticoido a la angdala.
Rutishausoi y sus cologas inloinaion una sola unidad
2/
varantes de amnesa y formas de |as enfermedades asocadas o trastornos de conducta
Amnesa q|oba|
Una diagnosis anticuada que implica p rdida de la memoria total (es anticuado porque en mayor a amn sicos
generalmente se conservan mediante el procedimiento de procesamiento impl cito y sistemas de cebado)
amnesia anter grada
Incapacidad para adquirir, almacenar o recuperar informaci n nueva a largo plazo y
conscientemente despu s de un incidente de p rdida de memoria
Amnesa retr|qrada
Incapacidad para reactivar conscientemente informaci n fue almacenada hace mucho tiempo
Amnesa parca| (amnesa |acunar)
P rdida de la memoria que se limita a determinados tipos de informaci n o la vida de las pocas
Amnesa c matera|-spec|
Nomenclatura deterioro con respecto a objetos o materiales
Amnesa autoboqr|fca
Incapacidad para recordar acontecimientos (y a un conocimiento personal de menor grado)
de la propia vida sem ntica amnesia
Incapacidad para reactivar hechos generales, o las expresiones ling sticas (menor
frecuencia) (como en la demencia sem ntica)
Amnesa topoqr|fca
Disturbio de la memoria para ubicaciones y espacio
aramnesa redup|catvo
Perturbado sentido de familiaridad; el paciente estconvencido de que una persona, lugar u objeto existe dos
veces (repetidamente); generalmente causada por da o cerebral org nico (es decir, neurol gicamente
basado) S ndrome de Capgras (delirio)
Perturbado sentido de familiaridad; el paciente asume que un familiar o amigo cercano ha sido reemplazado
por un impostor, o doble; generalmente sin s ntomas alucinatorios, pero subsumed bajo enfermedades
psiqui tricas
Amnesa nfant|, n|e|
Incapacidad para recuperar conscientemente eventos desde el primer remate de 3 4 a os
de vida (probablemente causado por insu cientemente desarrollado cerebro, uno mismo y el
lenguaje y la existencia de recuperaci n de memoria de estado dependiente)
Amnesa de| desarro||o
Amnesia epis dico-autobiogr fica con memoria sem ntica conservada
despu s de eventos hip xico-isqu mica sostenido generalmente dentro del
primer a o de remate de vida
S|ndrome/amnesa de korsa|o|
Un s ntoma de aglomerado con amnesia anter grada severa, amnesia retr grada variable,
confabulaciones y una desorientaci n con respecto a tiempo y lugar; con frecuencia se conservan la
inteligencia y la memoria a corto plazo; generalmente causado por uso indebido de alcohol severa y a largo
plazo, pero principalmente un desorden de la desnutrici n con un patr n distinto de principalmente la
degeneraci n cerebral diencef lico medial
seudodemenca
Amnesia-como los s ntomas pueden ser evidentes, pero la causa primaria del trastorno
se basa en una enfermedad depresiva
S| ndrome de| b|o|ue mnestc
Bloque de memoria, causada por factores psicolgicos como el estrs
severo o trauma psicolgico
(Contin a en la p gina siguiente)
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i]2 www.thelancet.com vo| ]8u October 2u, 2ui2
activity in hiocanus and anygdala coiiolatod
ositivoly with succosslul iocolloction ol ioviously
oicoivod stinuli. EAM inaiinonts night acconany
Uilach-Wiotho disoaso, a gonotic disoidoi associatod
with lilatoial anyg dala calci cations.
28
Evidonco that tho MTLaiticulaily tho HFlayod a
najoi ait in nonoiy ist aoaiod in alout 1900, 1
howovoi, no-ono locusod on MTLs association with
nonoiy until 195/ whon Scovillo and Milnoi iooitod
ationts with lilatoial MTL suigoiy socondaiy to
intiactallo oilosy. Within this soiios, tho caso ol ono
29
ationtknown as HMlocano lanous. HM was
ooiatod on in 1953 and diod in 2008. At tho tino ol
suigoiy ho had noinal intolligonco and nonoiy lunction.
Altoi suigoiy ho lost his alility to consciously loin now,
stallo long-toin nonoiios, although his ioooiativo
sonantic and iocoduial nonoiios ionainod laigoly
intact. Initial dosciitions suggostod that ho could iotiiovo
nost ol his old autoliogiahical ovonts. Latoi studios
iovoalod that ho could still acquiio inloination that was
iocossod at tho lovols ol conditioning, iining, and
iocoduial nonoiy. Inaging that was undoitakon alnost
loui docados altoi suigoiy iovoalod that HM had
undoigono lilatoial ionoval ol tho anygdala,
aiahiocanal-ontoihinal coitox, and antoiioi
hiocanus.
Sinco tho ist iooits ol HMs nonoiy do cits, HF
(including hiocanus iooi, dontato gyius, and
suliculun was thought to lo tho najoi hul loi
tiansnission ol inloination lion shoit-toin to long- toin
stoiago, and this viow iocoivod suoit lion sulsoquont
woik in oolo and aninals. Pathological changos to HF
woio thought to undoilio annosic disoidois causod ly
MTL oilosy, viial inloctions, hyoxia, oi cailon nonoxido
oisoning. Howovoi,
30
invostigatois
havo quostionod how soloctivo ationts liain danago is
altoi thoy havo had thoso disoidois. 31,32
Foi oxanlo, hoios sinlox oncohalitis night load to
dogonoiation ol tho antoiioi and nodial tonoial lolos
and oilitoliontal coitox.32
HF atiohy gonoially acconanios oaily Alzhoinois
disoaso, lut was also notod in non-donontod oldoily
oolo. Foi tho ast low yoais, iosoaichois havo 33
attontod to dioiontiato, within tho HF, activations
duiing oncoding lion acti vations duiing iotiioval and
32
di oiont loins ol nonoiy (sonantic nonoiy, EAM, and
satial nonoiy. Studios iooiting that ationts
32
with danago to tho HF nd it di cult to inagino now
oxoiioncos oi io-oxoiionco oldEAMs ignitod nuch
34
intoiost, howovoi, sulsoquont invostigations into
35
inagination ol lutuio oxoiioncos in ationts with HF
danago did not yiold uniloin iosults, oihas locauso
thoio woio di oioncos in tho oxtont and onsot ol tho
danago, soloctivity ol losions, and tosting nothods.
36
Sovoial studios ol ationts with MTL annosia oi dioncohalic
annosia havo locusod on tho ossilility that iocolloction and
laniliaiity iocossos aio nouio ana- tonically soaiato.
Rocolloction is tho iocoss noodod to iocall associativo olononts
ol knowlodgo and soci c contoxtual dotails ol a iovious ovont
so that tho ast can lo io-oxoiioncod oi iolivod. Tho looling ol
laniliaiity is lasod on tho natching ol iocossos lotwoon
iotiioval cuos and nonoiy ioiosontations, in tho alsonco ol
iocol- loctivo oxoiionco. Shoitconings ol studios attonting to
(Continued from previous page)
Dssocatve amnesa
Psychiatric disorder characterised by an inability to recall personal information that is
underlain by the psychological mechanism of dissociation
Dssocatve fuque
Form of dissociative amnesia that is characterised by the patient leaving their place of
living (their home)
Dssocatve dentty dsorder (mu|tp|e persona|ty dsorder)
Existence of two or more personalities or personality states; amnesia for everyday events
is a common feature and personalities are usually amnesic towards each other
uanser syndrome
Dissociative disorder solely de ned when a patient gives approximate answers to
questions; its original description also included hysterical semitrance, amnesia, and hallucinations
sychoqenc amnesa
Broad term that refers to amnesic disorders that are linked to psychological factors; it makes
no a-priori assumption about the nature of the associated psychological mechanisms
!unctona| amnesa
Amnesia usually without evidence of brain damage on conventional structural imaging,
and of an unsure cause
osthypnotc amnesa
Inability to recall events that occurred during hypnosis
1ransent q|oba| amnesa
Massive anterograde and partial retrograde amnesia, usually of elderly people (>60 years),
lasting less than 24 h; it is thought to be benign and is usually triggered by physical or
psychological stress factors
1ransent ep|eptc amnesa
Recurrent, transient episodes of isolated memory loss usually lasting less than 1 h;
a subtype of temporal lobe epilepsy
Amnestc m|d coqntve mparment
Subtype of mild cognitive impairment characterised by a decline in memory beyond
age-correlated benign forgetfulness and with a higher likelihood of progression to
Alzheimers disease than other forms of mild cognitive impairment
ost-traumatc amnesa
Term used in publications about traumatic brain injury; sometimes it describes the phase
after the resolution of delirium that is characterised mainly by memory impairments;
sometimes the term overlaps with delirium, encompassing a period from injury until
recovery of full consciousness and memory
!eqned amnesa
Feigned memory impairments or intentional exaggeration of existing memory
impairments, possibly motivated by external incentives (in the case of malingering) or
the intrapsychic need to assume the sick role (such as in factitious disorder)
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discovoi which liain iogions aio inlicatod in soci c
iocossos includo tho snall nunloi ol study ationts and
Panel 2:
tho low soloctivity ol thoii losions.
Gilloa and colloaguos aiticlo, iooitodly on hio-
3/
canal contiilutions to iocolloction, stonnod lion ndings
lion two ationtsono with lilatoial loinix and sotal nucloi
losions and nild coitical and hiocanal

atiohy (tho hiocanus is in lact a cononont ol tho
coiolial coitox, and tho othoi with tiaunatic liain injuiy
with widosioad linlic and noocoitical danago ol all coitical
lolos. Dosito tho low nunloi ol casos and tho
non-soloctivity ol tho liain danago, tho invostigatois still
concludod that tho oxtondod hiocanal syston is ioquiiod
to suoit iocolloction.
3/
In a thoughtlul thooiotical analysis lasod on
quantitativo nodolling, Shinanuia concludod that iotiioval ol EAM
38
is a wholo-liain oxoiionco in which tho hiocanus
iooi can lo viowod as sitting at tho to ol a hioiaichy ol
MTL stiuctuios, all ol which aio doondont on luithoi
sonsoiy and onotional inloination iocossing iogions.
This viow is tho sano as tho ono ioosod in guio 3 ol
HJMs iooit ol sychogonic annosia. Di oiing
39
thooiios oxist alout whothoi tho iotiioval ol old auto-
liogiahical nonoiios occuis indoondontly lion MTL
stiuctuios such as tho HF, oi whothoi thoso stiuctuios
aio ongagod in addition to noocoitical notwoiks. Tho
standaid nodol assunos that nowly consolidatod
40
inloination loconos indoondont ol tho hiocanus
altoi sono tino, whoioas tho nultilo-tiaco nodol
41
assunos that hiocanal iogions ionain ongagod
duiing iotiioval loi tho duiation ol that oisons lilo.
Winocui and colloaguos loinulatod a conioniso ly 42
suggosting that loss intogiatod, schonatic voisions ol
oiiginal EAMs locono indoondont ol tho hiocanus,
whoioas thoso with contoxtual dotails ionain doondont on
tho hiocanus.
A social vaiiant ol MTL annosia is dovolonontal
annosia, which is thought to lo causod ly soloctivo
danago to hiocani duo to nouional loss (usually
loading to at loast a 3040% ioduction in lilatoial voluno
ol hiocani conaiod with contiols. It night lollow
oisodos ol ischaonic hyoxia, occuiiing oiinatally oi in
childhood. Childion with dovolonontal annosia can
acquiio and iotiiovo lacts, lut thoii acquisition and
iotiioval ol EAMs is gioatly inaiiod. Thoso ndings
onhasiso that HF is a koy stiuctuio in tho loination ol
lasting EAMs.
Studios ol young adults with dovolonontal annosia
havo oxloiod tho alility ol thoso ationts to inagino
tho lutuio
laniliaiity voisus iocall]iocolloction.
43,44
and dioioncos lotwoon iocognition]
With iosoct to
454/
inagination ol lutuio oisodos, only ono ol tho two
43
idonti od do cits, dosito sinilai hio- studios
canal voluno ioductions (50%. This nding waiiants
43,44
tho nood loi additional invostigations into tho contii-
lution ol iosidual hiocanal tissuo in tho
inagination ol lutuio ovonts conaiod with tho contiilution ol
othoi stiuctuios. Bosidos hiocanal alnoinalitios, oldoi
studios ol dovolonontal annosia dosciilod sono changos
to tho utanon, thalanus, and iight iotioslonial coitox.
With iosoct to iocog nition]
45
laniliaiity voisus iocall, a dis iooitionally high
inaiinont in lioo iocall was con sistontly iooitod,
46,4/
which is a iosult not always dosciilod in hiocanal
48
danago ol adult onsot. Pationts with dovolonontal
annosia soon thoioloio to havo do cit attoins that
aitly ovoila with thoso ol ationts who acquiiod thoii
hiocanal alnoinalitios in adult hood, sug- gosting
that hiocanal danago night load to soci c
vaiiations in honotyo, doondont on tho onsot ol tho
danago.
Tho iototyo ol dioncohalic annosia is Woinicko-
Koisako s syndiono, which is chaiactoiisod ly loth
antoiogiado and iotiogiado inaiinonts ol EAM, and
occasionally ly inaiinonts ol sonantic nonoiy, and
conlalulations.
49,50
individuals with chionic alcohol nisuso and concuiiont
Tho syndiono tyically occuis in
Medca|, substance-re|ated, psychatrc, and atroqenc causes of
amnesc dsorders
Medca|
Head injury (closed or penetrating)
Stroke (ischaemic or haemorrhagic)
Aneurysmal bleeding (subarachnoid haemorrhage) or aneurysm surgery
Medial temporal lobe epilepsy
Intracranial tumour
Limbic encephalitis due to infections (herpes simplex virus 1 and 2,
he rpes zoster virus, and human herpes virus 6 in transplant
re cipients), of paraneoplastic origin, or associated with autoimmune
di seases (eg, systemic lupus erythematosus, voltage-gated potassium
ch annel antibody-associated encephalitis, or encephalitis associated with antibodies against N-methyl-D-aspartate receptor)
Neurosyphilis
Vitamin de ciencies (vitamin B1 de ciency)
Transient global amnesia
Transient epileptic amnesia
Substance-re|ated
Chronic alcohol misuse/vitamin B1 de ciency (Korsako s syndrome)
Drug misuse: anxiolytics (benzodiazepines), sedative-hypnotics (barbiturates,
zo lpidem) Anticholinergics
sychatrc
Dissociative amnesia
Dissociative fugue
Dissociative identity disorder (multiple personality
di sorder) Dissociative trance disorder
latroqenc
Drug side-e ectseg, of anticholinergic drugs including antidepressants (tricyclic and tetracyclic
antidep ressants), antipsychotics, or antiparkinsonian agents with anticholinergic properties (eg,
benzatr opine), and anaesthetics
Surgical procedures on brain
Electroconvulsive therapy
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thianino docioncy, oi with othoi disoidois associatod
with thianino do cioncy. Bocauso ationts with
49
chionic alcoholisn night also dislay EAM inaii-
nonts and do cits in woiking nonoiy, notanonoiy,
and oxocutivo lunctions, thoio night lo a continuun 51
lotwoon syntons ol alcoholisn and Koisako s
syndiono. Biain alnoinalitios in ationts with
51
Koisako s syndiono night soon to lo noio
widosioa d (including tho niddlo cingulato gyius whon
noasuiod ly changos in liain glucoso notalol- isn
than whonassossod ly ost-noiton analysos.
51
Post-noiton ndings nainly oint to tho dogonoiation
ol nidlino di oncohalic stiuc tuios, lut do not con in
whothoi, in addition to tho usually a octod nannillaiy
lodios, dogonoiation occuis in tho nodiodoisal thal- anic
nuclous (oi j ust its nodial, nagnocollulai oition oi tho
aiataonial nucloi situatod nodially to tho nodiodoisal
nuclous.
Studios ol ationts with noio soloctivo lilatoial
nodiodoisal oi antoiioi thalanic nucloai danago havo
ointod to tho association ol thoso aiataonial nucloi with
nonoiy. Fuithoinoio, sovoial iooits havo 52
iovidod ovidonco that lilatoial danago to tho nan-
nillaiy lodios oi tho nannillothalanic tiact (oi ovon to
tho tognontal nucloi ol Guddon with lidiioctional
connoctions with tho nannillaiy nucloi is su ciont to
causo annosia. Eailioi iodictions linking di oiont
53
asocts ol nonoiy iocossing (laniliaiity voisus
iocolloction to tho antoiioi oi nodiodoisal thalanus
woio not con inod. Howovoi, invostigatois havo now 52
ioosod that nannillothalanic oi antoiioi nucloi
danago iolally loads to do cits in iocolloction,
whoioas danago to tho vontial anygdalolugal athway oi
nodio doisal nuclous a octs laniliaiity iocossing.
54
Thalanic danago is nost connon altoi stioko. Foui
aitoiial lianchos vasculaiiso di oiont thalanic iogions
and can lo a octod oithoi in conlination oi
individually, loading to distinct syntons (aondix.
55
Tho lasal loioliain is conosod ol thioo najoi nucloai
conloxos nado u ol nouions containing acotylcholino
(and -aninolutyiic acid: lasal nuclous ol Moynoit,
diagonal land ol Bioca, and sotal nucloi. Thoso nucloi
iojoct to tho HF and othoi coitical aioas. Tho (nodial
sotal iogion is connoctod to tho anygdaloid conlox.
Tho anygdaloid conlox onhancos tho onotional
iolovanco ol inloination whilo tho sotal nucloi aio
thought to oxoit an oosito, danoning o oct. Basal
loioliain annosia can occui altoi iutuio and suigoiy ol
anouiysns ol tho antoiioi connunicating aitoiy and
tunouis. Clinical di oioncos lotwoon lasal loioliain
annosia and MTL oi dioncohalic annosia nainly aiiso
locauso ol tho location ol tho lasal loioliain nucloi in
tho onunlia ol tho vontial ioliontal coitox. In lasal
loioliain annosia, oxocutivo dyslunctions aio connon,
and iocallioquiiing activo o oitis noio inaiiod
than iocognition ol inloi nation. Il tho danago oxtonds
to
56
uoi oitions ol tho liontal lolos, souico annosia
(lailuio to iononloi whoio inloination cano lion
night occui. Danago to lasal loioliain associatod 5/
with anouiysns ol antoiioi connunicating aitoiios can
load to onhancod vulnoialility to iovokod
conlalulations and lalso iocognition in iocoduial
nonoiy (tallo 1.
58
Panel 3:
memory dsturbances
8ran reqons whose (b|atera|) damaqe s fo||owed by characterstc
Meda| tempora| |obe (especa||y hppocampa| formaton and surroundnq structures) Lncodnq and
conso|daton of LAM and semantc memory nto the |onq-term store, spatotempora| nteqraton
Amyqda|od comp|ex
Assessment of biological and social signicance; emotional tagging of memories,
especially of episodic-autobiographical memory
refronta| cortex
Short-term memory (dorsolateral prefrontal cortex); encoding and recall of episodic and
semantic information (especially e ortful recall)
Orbtofronta| cortex, basa| forebran
Encoding and emotional connections to information; control and suppression of
confabulatory tendencies
Lmbc tha|amc nuc|e, fornx, mamm||ary bodes
Binding and association processes for transfer into long-term storage; consciousness
u|vnar
Processing, especially of language-related information, attention, and semantic memory
Cnqu|ate qyrus
Processing of components of memory related to attention and wilful acts
ketrosp|ena| cortex, precuneus
Imagination; representation of memories; familiarity
Latera| pareta| cortex (especa||y |eft)
Short-term memory; mediation of mnemonic processing by attention
8asa| qanq|a
Procedural memory processing
M1L D 8!
Abilities of conscious reection and self-awareness
Tendencies of disinhibition and perseveration
+ +/ /+
+/ /+
Anosognosia
Initial loss of the sense of time (chronotaraxis)
/+ +
/+
Disproportional impairment of recall as opposed to recognition + Tendency to confabulate
/+ +
Decits in tasks needing executive functions
Emotional instability and mood disorders
+/ +
/+ +
Di culties with attention and concentration +
Damage to the region is (+) associated; (
this characteristic.
) not associated; (+/) often associated; or (/+) occasionally associated with
Table 1:
forebran (8!) damaqe
Characterstcs of amnesas re|ated to meda| tempora| |obe (M1L), dencepha|c (D), and basa|
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whte-matter damaqe and amnesa as a
dsconnecton syndrome
Tho occuiionco ol annosia altoi lio tiact danago was
ist iooitod sono tino ago. Sovoial lio lundlos aio ol
1
social intoiost in nonoiy iocossing locauso thoy
intoiconnoct iolovant lottlonock stiuctuios
9,59,60
aon dix. Tho loinix connocts all thioo najoi iogions
(soo
that aio inoitant loi nonoiy consolidation and tiansloi
into long-toin nonoiy (MTL, dioncohalon, and lasal
loioliain. In a study ol 38 ationts who had undoigono
colloid cyst ionoval, signi cant nogativo coiiolations
woio iooitod lotwoon loinix voluno and iocall in
standaidisod nonoiy tosts. Filios assing thiough tho
61
intoinal and oxtoinal casulos (osocially thalanocoitical
connoctions and tonoial ston (osocially tho uncinato
lasciclo connocting ioliontal, anygdalai, and tonoial
aioas iovido inoitant links that conloto tho notwoik
ol linlic and aialinlic iogions (ioliontal and tonoial
lolos, and dioncohalon, and thoii danago can load to
nonoiy do cits.
62
Mosulan and othois iooitod tho oxistonco ol laigo-
63
scalo notwoiks loi nnononic iocossing. Functional
nouioinaging onallod tho chaiactoiisation ol laigo-scalo
liain systons, such as tho dolault nodo notwoik, which
has lunctions in iosoction and EAM. Alnoinal dolault
64
nodo notwoik activity was iooitod in annostic nild
cognitivo inaiinont and oaily Alzhoinois disoaso.
64
Whito nattoi onsuios iooi ow ol inloination in
liain notwoiks. Stiuctuial inaging tochniquos, such as
di usion tonsoi inaging and nagnotisation tiansloi
iatio noasuionont, iniovod tho alility to ostinato tho
intogiity ol whito nattoi in nonoiy-inaiiing dis oidois.
Invostigatois using nagnotisation tiansloi inaging in a
ationt with lunctional annosia iocoidod sultlo changos
in whito nattoi in tho iight ioliontal aioa. Whito-
65
nattoi danago occuis in sovoial illnossos, such as
nultilo scloiosis (in which nonoiy di cultios aio
connon. Soulcio and colloaguos idonti od danago 66
to nany lio tiacts, osocially thoso iunning thiough tho
tonoial ston and intoinal casulo, in a laigo sanlo ol
ationts with nultilo scloiosis. Whito-nattoi danago is
connon inationts who havo had a stioko. Stioko is tho
only causo ol annosia that can a oct all nonoiy-
iocossing stiuctuios ol tho linlic syston.
6/
Tiaunatic liain injuiios iosulting in di uso (nultilocal
axonal injuiy night also load to distuilancos in antoiogiado
and iotiogiado nonoiy. Ono toic ol 6
continuing intoiost is tho iolation lotwoon tiaunatic
liain injuiy, in aiticulai (concussivo nild hoad injuiy,
and sychogonic oi lunctional annosia.
To what
11,65
oxtont tho iutuio ol no connoctions lotwoon synasos
and dondiitos night causo widosioad coiolial dyslunction
is uniosolvod, and whothoi tho tiaunatic oxoiionco itsoll
can load to a sychologi cal shock disoidoi, which thon
night iosult in sovoio and oisistont annosia and othoi
cognitivo distuilancos, i s also unknown. Incidontally,
liain concussions at
13
vaiious locations along tho skull can load to annosia
that is nainly iotiogiado.
6
Amnesas wth mxed psycho|oqca| and
physo|oqca| causes
Tiansiont glolal annosia haons suddonly, usually in
adults oldoi than 60 yoais, and is tiiggoiod ly hysiological oi
sychological lactois. Its couiso is 68
lonign locauso it (tyically disaoais within a day.
Slight nonoiy do cits night, howovoi, oisist loi
nonths, osocially il ationts continuo to havo anxioty oi
doiossion. Tiansiont glolal annosia a octs nostly
69
antoiogiado nonoiios, lut can aitly a oct iotiogiado
nonoiios as woll. Tho causo ol tiansiont glolal
/0
annosia is still olusivo, although hyothosos havo
suggostod that snall thionli in doo coiolial voins oi
/1
intoinal jugulai voin valvo in conotonco night lo to
/2
llano. Baitsch and Douschl onhasisod that tho
/0
vulnoialility ol tho coinu annonis (CA1 nouions ol
tho hiocanus to notalolic stioss is ivotal in tho
athohysiological cascado undoilying tiansiont glolal
annosia. Tho tiansiont glolal annosia iocuiionco iato
is sulstantial (610% oi yoai.
/0
Di oiontial diagnosos ol tiansiont glolal annosia includo
tho iocuiiont shoitoi-lasting oisodos ol tiansiont oilotic
annosia, which can occui on awakoning in individuals ol
niddlo and old ago (noan ago ol 5/ yoais. Pationts with
tiansiont oilotic annosia olton conlain ol oisistont
intoioisodic nonoiy do cits. Although oljoctivo noasuios
on standaid tosts ol antoiogiado nonoiy can lo noinal,
accoloiatod long- toin loigotting loi days to wooks and do
cits ol ionoto EAM woio docunontod.
/3
Functional, sychogonic, oi dissociativo annosias
night lo associatod with sychological lactois co-occui-
iing with a (ninoi hysical injuiy. Thoy aio gonoially
diagnosod in oolo agod 2040 yoais and chaiactoiisod
ly iotio giado EAM inaiinonts. Occasionally, antoio-
giado annosia in tho alsonco ol iotiogiado EAM
inaiinont night tako laco.
13
Tho nochanisn ol dissociation undoilios dissociativo
annosia, which is linkod to sychological stioss in
19
vaiious cultuios. Psychogonic annosia consists ol
13
disoidois with vaiious sychological nochanisns. Not
13
all lunctional annosias aio diagnosod with a do nito
lackgiound ol sychological lactois.
13
Lpdemo|oqy and qenetcs
Eidoniological data aio availallo loi only soci c
annosic disoidois. Tho incidonco ol tiansiont glolal
annosia is 38 oi 100 000 oolo oi yoai. Hoad tiauna is tho nost /0
iolallo causo ol annosic disoidois that aio duo to a
gonoial nodical disoidoi. Although docioasos in tho
incidonco ol thianino-iolatod disoidois woio iooitod in
sovoial countiios altoi loiti cation ol lioad with thianino,
an incioaso in tho incidonco ol Koisako s syndiono was
dosciilod in sono Euiooan countiios. Foi dissociativo
49
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annosia, a 12 nonth iovalonco ol 18% was iooitod in a
US connunity ol 658 adults.
/4
Tho gonotic undoiinnings ol hunan annosia aio still
unknown. Studios ol tho gonotics ol Koisako s syndiono and
tiansiont glolal annosia yioldod no conclusivo iosults.
as an intoinodiato honotyo in annosic disoidois,
49,/5
Although EAM inaiinonts could lo iogaidod
/6
which night lo ioxinal to thoii undoilying gonotic iisk,
data alout how gonotics a oct EAM aio inconclusivo.
Sovoial iosoaichois stato that alout 50% ol tho intoi-
individual vaiialility in nonoiy alility is attiilutallo to
gonotic lactois, this assoition is, howovoi, lasod on
/6
iosults ol lohaviouial gonotic twin studios that did not
//
uso EAM tosting aiadigns in accoidanco with tho
iosont do nition ol EAM.
3
Woik in aninals iontod sovoial hyothosis-diivon
lohaviouial and inaging gonotic studios that invostigatod
tho association lotwoon nonoiy oiloinanco in di oiont
oulations and vaiiants ol sovoial candidato gonos.
/6
Sovoial iosoaichois havo dono gonono-wido association
studios to tiy to nd associations lotwoon vaiiations ol
/8
di oiont gonos (tallo 2 and oisodic nonoiy oiloi-
nanco.
nost studios that iooitod to havo invostigatod an
/6,/9,80
Howovoi, aait lion ono ninoi oxcotion,
81
association lotwoon ono ol tho dosciilod gono vaiiants
and oisodic nonoiy did not uso EAM tosting aiadigns
that woio congiuont with EAMs do nition.
/6,/9,80,82
Bocauso EAM is a conlox nouiocognitivo syston, it is
iolally a octod ly gonos, onviionnont, and thoii
intoilay. Tochnological iniovononts and tho uso ol
nothodological iigoui with iosoct to EAM tosting
aiadigns night hol us to lottoi undoistand EAMs
gonotic loundation.
Assessment of amnesc dsorders
Assossnont ol annosic disoidois includos anannosis and
nodical, laloiatoiy, and occuational-thoiay ovaluations
(soo aondix loi a ow diagian on assoss nont
stiatogios. Nouiosychological tosting is invaluallo to
oljoctivoly ostallish tho natuio and sovoiity ol tho nonoiy
inaiinont, to quantily longitudinal changos, and to
distinguish lotwoon annosias ol di oiont causos and
loignod annosia. Cognitivo distuilancos duo to inlaict oi
closod hoad injuiy can chango ovoi tino. Fuithoinoio,
studios sonotinos iooit discioancios lotwoon suljoctivo
conlaints and oljoctivo noasuionont oi suggost
21
oxaggoiation oi ioducod o oit.
56
Vaiious aioachos attont to di oiontiato loignod lion
tiuo annosia. Many aio lasod on tosting with concoalod
lovols ol di culty and uso o oit noasuios ,
roduct resumed functon n memory
WWC1 KIBRA (a scaolding protein, highly expressed in
hippocampus/temporal lobe)
Long-term memory acquisition and storage; interaction with
protein kinase C/M; recall
CLSTN2
PDYN
Calsyntenin-2 (a synaptic protein)
Prodynorphin (endogenous opioid, precursor of
Interactive e ect with KIBRA
Memory acquisition
dynorphins)
Catechol O-methyltransferase (enzyme implicated in the
COMT catabolism of monoamines [dopamine and
noradrenaline])
Encoding; arousal-mediated consolidation
PRNP
CPEB3
Prion protein
Cytoplasmic polyadenylation element-binding protein 3 Memory formation and maintenance
Long-term memory formation and maintenance
GRM3
CHRNA7
Metabotropic glutamate receptor 3
Neuronal acetylcholine receptor subunit alpha-7 Learning and memory
Memory formation
HTR2A
Genes of the protein kinase A
5-hydroxytryptamine receptor 2A
Protein kinase A enzymes
Modulation of serotonin transmission; memory formation
Late-phase of long-term potentiation; memory consolidation
enzyme family
Genes of the protein kinase C
enzyme family
Protein kinase C enzymes
Maintenance of long-term memories (protein kinase C /M )
BDNF
polymorphism)
(valine66 to methionine Brain-derived neurotrophic factor (a neurotrophin) Regulation of synaptic plasticity (long-term potentiation and
long-term depression); encoding and retrieval
SLC6A4
transporter-linked polymorphic
(5-HTTLPR [serotonin-
region])
Sodium-dependent serotonin transporter Serotonin re-uptake; encoding and consolidation
APOE ( allele combinations) Apolipoprotein E Lipid transport protein implicated in maintenance and repair of
neuronal cells; regulation of deposition and formation of
amyloid plaques and neuro brillary tangles
CNS cholesterol homoeostasis CETP
[isoleucine to valine V405])
(SNP at codon 405 Cholesteryl ester transfer protein
CTNNBL1 Beta-catenin-like protein 1 (brain-expressed) Memory encoding and consolidation
SNP=single nucleotide polymorphism.
Table 2: uenes proposed to be assocated wth epsodc-autoboqraphca| memory or epsodc memory performance
kevew
www.thelancet.com vo| ]8u October 2u, 2ui2 i]/
iocognition (loicod-choico aiadigns, oi calculation
alilitios (soo guio 1 ol Yochin and colloaguos . Tho
83,84
idoa is to iovido tho otontial loignoi with a sulstantial
85
anount ol sinlo inloination and to convoy tho
iniossion ol a di cult nonoiy task, whon in ioality it
is not di cult (hoalthy oolo oiloin at tho uoi
linit. Rosults lion sychological oxoiinonts show
84
that wo aio oasily allo to iocogniso an onoinous nunloi
ol ictuios and aio tyically nuch lottoi at iton
iocognition than at iton (lioo iocall. Fuithoinoio, wo
oiloin duiing lioo iocall in a tyical attoinnanoly,
in a loaining cuivo with a iinacy and a ioconcy o oct.
Howovoi, loignois night show atyical oi inconsistont
oiloinanco on systonatic tosting. Stiuctuiod invontoiios
can aid with dotoction ol nalingoiing in loionsic oi
litigation casos. Functional nouioinaging can lo usod
84
to invostigato nouial coiiolatos ol lalso nonoiios and
loigning. Rosults aio still divoigont, and dosigns that aio
86
noio ocologically valid aio loing tostod.
8/
In annosic disoidois, tho acquisition ol a nulti-
dinonsional io lo is advisallo. Usually, lolt-
honishoiic danago nainly loads to voilal nonoiy
inaiinonts, whoioas iight-honishoiic danago a octs
non-voilal nonoiy do cits. Shoit-toin nonoiy is only
iaioly a octod.
Tho ationts intolligonco should always lo noasuiod oi
at loast ostinatod. Bocauso low lovols ol attontion and
concontiation can inaii tho acquisition ol now
inloination, thoii noasuionont is ossontial. Di oi on ti-
ation lotwoon nonoiy noasuios ol lioo iocall (activo
inloination gonoiation, cuod iocall, and iocognition is
inoitant. Pationts, osocially thoso with liontal lolo
danago, night show a discioancy lotwoon iocognition
and lioo iocall. Tosts to assoss ationts with annosia
56
and ciitoiia loi assossnont ol iotiogiado EAM
inaiinonts aio dosciilod in tho aondix.
roqnoss and treatment of amnesc dsorders
A low annosic disoidois (such as tiansiont glolal
annosia havo good iognosis, othois aitly iniovo,
and loi sono disoidoisosocially thoso with conloto
lilatoial danago to MTL, dioncohalon, oi lasal loio-
liainiognosis ionains ooi. Tiaditionally, nost casos
ol dissociativo annosia woio iooitod to iosolvo
sontanoously, howovoi, iooits havo sinco suggostod
that chionic loins oxist.
10,13
Paiontoial thianino givon ioutinoly to ationts at iisk
docioasos thoii likolihood ol dovoloing Woinicko-
Koisako s syndiono. Monoiy inaiinonts iolatod to
49
oloctioconvulsivo thoiay night lo ioducod ly unilatoial
oloctiodo laconont, titiation ol tho oloctiical cuiiont
accoiding to tho ationts soizuio thioshold,
and
21,22
ultialiiol ulsos.
88
Phainacological tioatnont data loi annosic disoidois
aio scaico and cono lion studios with snall nunlois ol
casos that olton do not havo a lacolo-contiol giou. An
oon-lalol, non-iandonisod study ol 11 ationts with
lasal loioliain annosia altoi anouiysn iutuio notod
voilal nonoiy iniovononts altoi a 12 wook tiial ol
510 ng donoozil oi day.89
A low lacolo-contiollod studios suggostod that
cholinostoiaso inhilitois could lo usod to addioss
chionic ost-tiaunatic nonoiy inaiinonts in ationts
with tiaunatic liain injuiy.
90,91
addiossod tho sycho haina cological (oi sychothoia-
No contiollod studios
outic tioat nont ol dissociativo annosia. Studios havo
12
lookod at novol diugs (histono doacotylaso inhilitois
1/
and sonatic (liain stinulation intoivontions that night
aid nonoiy iniovonont.
92
Thus, no ovidonco-lasod sychohainacological oi
sonatic tioatnonts aio known to lo do nitivoly o octivo at
iovoising nonoiy inaiinonts oi do cits in annosic
disoidois. Tho incioaso in giou studios and iaid advancos
in tho liological undoistanding ol nonoiy givo hoo to
tho dovolonont ol o octivo sycho haina cological and
sonatic intoivontions loi annosic disoidois.
Idoally, iohalilitation should addioss cognitivo, ono-
tional, and sychosocial lunctioning and iosoctivo
nonoiy. Gonoially, it consists ol tiaining stiatogios 93
aining to ostallish iovious lovols ol lunctioning and
cononsatoiy stiatogios. Inlicit tiaining stiatogios
with iocoduial and iining tasks havo loon
succosslully usod loi ationts with sovoio loins ol
annosia. Enhasis is laid on oiioiloss loaining
94
iocoduios and sonantic stiatogios. Succoss with
95
inlicit and oiioiloss loaining is not that connon and
96
cannot lo gonoialisod.
Suoitivo sychothoiay can onhanco iohalilitation
outconos loi ationts with iosoivod insight. Bosidos
conutoi-aidod tiaining, viitual-ioality onviionnonts 9/
aio usod loi nonoiy tiaining, and ovon non-invasivo
98
coitical stinulation has loon aliod. Rolianco on
99
oxtoinal nonoiy aids and suoit lion nodoin
conutoi-lasod oquinont is incioasing.
Evidonco-lasod data loi nonoiy iohalilitation aio
scaico. Cicoiono and colloaguos ioviowod class Ia
100 100
studios that iovidod ovidonco that visual inagoiy is
lottoi than standaid nonoiy tiaining, tho sano was tiuo
loi soll-instiuctod tiaining, at loast loi ationts with nild
nonoiy inaiinont. Tho uso ol oitallo agois was also
o octivo.
Howovoi, a dotailod ioviow on cognition-lasod intoi-
vontions in oldoi oolo, including nonoiy tiaining and
tiansloi ol tiaining o octs, statod that innodiato and
dolayod voilal iocall iniovod signi cantly thiough
tiaining conaiod to a no-tioatnont contiol condition, lut
tho iniovononts did not oxcood tho iniovonont in tho
activo contiol condition.
101
!uture drectons
Annosia in tho stiict sonsoio, a total and oxclusivo loss
ol tho alility to stoio now inloination consciously and
long toin, oi to iotiiovo long-toin stoiod inloination
consciouslyis iaioly lound. In lact, ioosals woio nado
kevew
i]8 www.thelancet.com vo| ]8u October 2u, 2ui2
ly tho DSM-V nouiocognitivo disoidois woik giou to
iolaco tho DSM-IV-TR catogoiy ol doliiiun, donontia,
annostic and othoi goiiatiic cognitivo disoidois with a
now catogoiy callod nouiocognitivo disoidois. Longitudinal
61:
studios ol (dissociativo annosia night lo noodod to
quantily ossillo cognitivo dotoiioiations ovoi tino. Tho
102
idonti
cation ol nouial coiiolatos ol vaiious annosias and iodictois
loi o octivo iohalilitation night lono t lion conlinod uso
ol lunctional and stiuctuial inaging. An undoistanding ol tho
(oigonotics ol nonoiy iocossos night hol with tho dosign
ol novol tioatnonts loi
21
annosias in tho lutuio.
Contrbutors
HJM and AS contiilutod oqually to tho nanusciit.
Con cts of nterest
Wo doclaio that wo havo no conicts ol intoiost.
Ac|now|edqments
Oui iosoaich was lundod ly tho Univoisity ol Biololold and giants lion tho
Clustoi ol Excollonco Cognitivo Intoiaction Tochnology (CITEC, EU
(NEST iogianno, Eyowitnoss Monoiy, FP6-043460, Goinan Rosoaich
Council (Bi 2894]1, 3, and Alliiod-Kiu Stiltung, Gioilswald. References
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