subarachnoid haemorrhage and akinetic mutism
TRANSCRIPT
SHORT REPORT
Subarachnoid haemorrhage and akinetic mutism
K. A. CHOUDHARI
Department of Neurosurgery, Regional Neurosciences Unit, Royal Victoria Hospital, Belfast, UK
AbstractTwo rare cases of akinetic mutism induced by aneurysmal subarachnoid haemorrhage are reported. The literature is reviewed,the possible pathophysiological mechanism of akinetic mutism is considered and the association between these two conditionsis explored with an attempt to address the roles of medical treatment and surgery and to discuss prognosis.
Key words: Akinetic mutism, aneurysm, anterior cerebral artery, cingulate gyrus, subarachnoid haemorrhage.
Introduction
Cairns and coworkers1 in 1941 introduced the term
‘akinetic mutism’ (AM) to denote a syndrome
characterized by lack of responsiveness in the presence
of apparently preserved vigilance.2 It is a neurological
state with total immobility (but not paralysis) except
for eye movements and complete absence of all other
types of communication.3 A person with akinetic
mutism has sleep-waking cycles. When apparently
awake, he may be able to indicate alertness with eyes
open, but lies mute, immobile and unresponsive. The
condition is known to be associated with trauma,
neoplasia and ischaemia of the brain.Two cases ofAM
associated with aneurysmal subarachnoid haemor-
rhage (SAH) are reported—one as a presenting feature
and the other as a delayed sequel of the SAH.
Comprehensive MEDLINE search was carried out
via theBritishMedicalAssociation’sOVIDMedline+
system, as well as via National Library of Medicine’s
PUBMED using ‘subarachnoid haemorrhage’ and
‘akinetic mutism’ as primary key words, initially
focused and exploded on these key words, and later
combined. Relevant literature is reviewed to explore
the anatomical association between these two condi-
tions, to discuss its pathophysiology andmanagement.
Illustrative cases
Case 1
A 41-year-old woman presented with collapse at work
and was thought to be unconscious at the scene. In the
casualty department, she was noticed to be in a state of
akinetic mutism. CT of the head showed an inter-
hemispheric clot situated dorsal to the corpus
callosum splaying the cingulate gyri (Fig. 1). There
was associated diffuse subarachnoid haemorrhage.
Angiography showed the presence of a saccular
aneurysm arising at the junction of left pericallosal
and calloso-marginal arteries (Fig. 2). This was
treated with right frontal craniotomy, clipping of the
aneurysm and complete evacuation of the clot via an
interhemispheric approach (Fig. 3). Her postopera-
tive course was complicated by chest infection and
vasospasm leading to further neurological deteriora-
tion. Onemonth later she improved to the state of AM
again. Very little improvement has been noticed after 3
months despite satisfactory radiological appearances.
Case 2
A 40-year-old woman presented with devastating
subarachnoid haemorrhage and remained comatose
for several weeks. An anterior communicating artery
(AComA) aneurysm was diagnosed, but was not
treated owing to the patient’s poor grade. It was
uneventfully coiled as an elective procedure after 6
months. Her condition at that stage was of akinetic
mutism. CT revealed infarcts in the distribution of
the distal anterior cerebral arteries (DACA). One
year following treatment she has shown very little
neurological improvement.
Discussion
Akinetic mutism (AM) describes a standard clinical
state characterized by akinesia (inability to move)
Received for publication 3 September 2003. Accepted 8 March 2004.
Correspondence: Mr K. A. Choudhari, Department of Neurosurgery, Regional Neurosciences Unit, Royal Victoria Hospital, Belfast BT12 6BA, UK.
Tel: + 44 (0)2890 635395. Fax: + 44 (0)2890 237733. E-mail: [email protected]
British Journal of Neurosurgery, June 2004; 18(3): 253 – 258
ISSN 0268-8697 print/ISSN 1360-046X online/04/030253–06 # The Neurosurgical Foundation
DOI: 10.1080/02688690410001732698
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and mutism (inability to speak). Although, its
clinical expression is fairly typical irrespective of
the cause, aetiological factors are diverse and
various anatomical sites are known to be involved.
Common neurosurgical causes of AM are summar-
ized in Table I. Non-traumatic AM is most
commonly caused by tumours arising from dience-
phalic structures or those arising in the midline
from the skull base4 or in the region of the third
ventricle. Common vascular causes of AM include
ischaemia of the basilar artery (BA) or the ACA4,5
territories, bilateral thalamic infarction of athero-
sclerotic origin,6 ACA dissection7 or, in rare
circumstances, purely due to abnormal morphology
of the ACA.8
Review of the literature
AM has been rarely linked directly to aneurysms and
aneurysmal SAH (Table II). A literature review
suggests that the most common cause of AM in
patients with SAH is secondary infarction in the
DACA territory.4,9 Sometimes post-SAH hydroce-
phalus has also been implicated in a delayed form of
AM following SAH.10 Rarely, low intracranial
pressure caused by decompressive craniectomy and
FIG. 1. Preoperative plain CT axial scan images showing interhemispheric clot with SAH.
FIG. 2. Angiogram showing distal anterior cerebral artery aneurysm (white arrow).
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theco-periotoneal shunt following SAH has been
reported to result in AM.11 AM has also been noted
during the natural course12 or recovery phase13 of
coma-producing SAH. Expanding or thrombosing
midline giant aneurysms are known to present with
AM without the SAH.14,15 AM as a presenting
feature of a poor-grade SAH as in our first case has
been sporadically reported,3,16 but is rare and usually
carries poor prognosis.
Pathophysiology of akinetic mutism
The syndrome of AM usually can be classified either
according to the anatomical site affected or depend-
FIG. 3. Postoperative CT scan showing satisfactory appearances, but residual hypodensities in the region of cingulate gyri.
TABLE I. Anatomical classification and neurosurgical causes of akinetic mutism
Anatomical level Structures affected Common pathologies
Telencephalic Cingulate gyri of the mesial frontal Lobes Vascular (ischaemic28, aneurysmal14,29), neoplastic
Diencephalic Thalamus (or thalamo-cortical tracts), caudate nucleus Neoplastic30, vascular (ischaemic)6, drugs31,32, hydrocephalus10
Mesenecephalic Upper brain-stem reticular activating system Traumatic 33
TABLE II. Akinetic mutism associated with Intracranial aneurysms and SAH
Author, year,
Reference
No of
cases
Cause of
AM
Site of the
aneurysm
Anatomical level
of the lesion
Patricolo, 197134 1 Postoperative complication AComA Hypothalamus
Buge,19754 1 Infarction of ACA region AComA Cingulate gyri
Koh, 197915 1 Mass effect caused by the aneurysm Basilar artery Mesencephalic compression
Von Cramon, 198035 1
Hydrocephalus and bilateral ACA
territory infarction AComA Cingulate gyri + diencephalons
Nemeth, 19883 1 Presenting feature of SAH
Left internal carotid
artery bifurcation Cingulate gyri
Nishigaya, 199036 1 Vasospasm in DACA territories DACA Cingulate gyri
Danilewicz, 199010 8 Secondary hydrocephalus – Diencephalic
Lechevalier, 199637 1 Infarction in the left ACA territory AComA Cingulate gyrus+dienecephalic ischaemia
Ushikoshi, 199927 1 Post- GDC coiling complication Superior cerebellar A Brain stem
Burruss, 19999 1 Unknown, intermittent – –
Hodozuka, 200011 1
Low pressure due to craniectomy
and T–P shunt AComA ?Diencephalic
Kanemoto, 200014 1 Mass effect caused by the aneurysm Azygous ACA Diencephalic compression
Present study 2
Intracerebral clot and DACA
territory infarction AComA and DACA Cingulate gyri
Subarachnoid haemorrhage and akinetic mutism 255
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ing on the underlying pathological condition. The
author prefers to classify it anatomically as:
. telencephalic (mainly affecting medial frontal
lobes- cingulate gyri;
. diencephalic (thalamic/basal ganglia);
. mesencephalic (upper brain-stem reticular
activating system; Fig. 4).
Two pathological mechanisms of AM can be
described:
. reduced ‘arousal’ of cortical function due to
lesions at or rostral to the meso-diencephalic
junction;
. impaired activation of the motor system
following bilateral damage to the frontal lobes.
Neither of these mechanisms in isolation is likely to
be responsible in the causation of AM and it is
possible that both mechanisms may play some roles
in varying combination in an individual case. Some
authors such as Ackerman et al., however, group the
frontal AM (type i in the anatomically-based
classification) separately from the mesodiencephalic
AM (types ii and iii in the anatomically-based
classification). Since perceptual and cognitive func-
tions are also severely disturbed in the latter variety,
they have labelled it as the ‘apallic syndrome’ if it is
in a milder form or ‘vegetative state’ if it is in its
extreme form, thus restricting the term ‘akinetic
mutism’ to reduced motor activation following
bilateral medial frontal damage.2 Unless the anato-
mical localization in a given patient is discrete, there
may be some overlapping of clinical features. This
may lead to usages of different terms interchangeably
by different authors, mainly depending upon their
perception of the severity of akinesia and mutism.
Thus, it appears that the conditions akinetic mutism,
apallic syndrome and vegetative state are not
mutually exclusive. Rather there is an overlap
between them and patients may improve or deterio-
rate from one into another.
In its classic form, regardless of the cause, the
underlying biochemical mechanism of AM is postu-
lated to be selective disruption of mesocoeruleo,
diencephalospinal and/or mesocorticolimbic dopa-
minergic pathways.17 Nemeth and colleagues, in
their study of akinetic mutism and locked-in
syndrome (LiS) analysed morphological observa-
tions in relation to the neurochemical findings and
found a consistent correlation between pathways of
dopaminergic neurons and the lesions associated
with AM. They concluded that dopaminergic sys-
tems are selectively damaged in AM but spared in
LiS.17 Echiverri et al. described reversible akinetic
mutism induced by bromocriptine in four children.18
Apart from isolated case reports, this theory has not
gained wide support in the clinical field, nor does it
tie in convincingly with the anatomical subtypes
described above. In cases where routine imaging
(CT/MRI) is not able to pin-point the anatomical
site affected, Tc99m brain SPECT imaging is said to
be of localizing value.19
Role of cingulate gyri
Aneurysmal SAH classically results in the frontal or
telencephalic AMwith affection of cingulated gyri and
almost always from aneurysms in the region of
anterior cerebral arteries. Each cingulate gyrus has
complex reciprocal connections with other limbic
structures and frontal cortex, and appears to provide
an interface between the decision-making process of
the frontal lobe and the emotional world of the limbic
system. Stimulation of the cingulate gyrus in humans
often produces negative or positive feelings, and in
lower animals, stimulation causes erection of the penis
and grooming. Most cases of aneurysmal AM result
from destruction of both cingulate gyri manifested by
immobility and speechlessness. Conversely, increased
activity in this region may contribute to Tourette’s
syndrome, characterized by increased movement
such as muscular and vocal tics, facial grimacing,
pacing, twirling, coughing, sniffing and grunting.
Medical treatment
AM caused by primarily neuronal damage may have
slightly better prognosis than that caused by mainly
white matter disruption and may also show better
response to medical therapy than the latter. Several
workers have reported encouraging response of the
AM state to medical treatments with agents like
levodopa20,21 or bromocriptine18,22 – 26 However,
AM in all these cases has been meso-diencephalicFIG. 4. Schematic diagram depicting various anatomical regions
affected in akinetic mutism.
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in contrast to the AM seen after SAH that is mostly
telencephalic (frontal). Although there is no strong
evidence to support routine administration of these
medications, a short therapeutic trial with dopamine
agonists may not be unjustified in cases of SAH-
induced AM if spontaneous improvement plateaus.
Role of surgery and prognosis
The author believes that SAH presenting with AM
carries similar prognosis to that of any poor-grade
SAH despite a preserved sensorium. In most
literature reviews, the presence of AM invariably
led to poor outcome irrespective of whether AM was
present before or after the treatment of the aneur-
ysm. The only exception seems to be that resulting
from secondary hydrocephalus, where promising
results have been reported.10 At our Institute, we
have achieved good results by radical evacuation of
intracranial clot together with clipping of the
ruptured aneurysm in poor-grade SAH patients
(unpublished). However, our efforts to radically
evacuate the clot and to treat the aneurysm urgently
in an attempt to reverse the AM (case 1) have yielded
slightly disappointing result. The author now be-
lieves that, in the absence of a localized haematoma,
acute surgical intervention may, in fact, worsen a
patient’s neurological condition if the patient already
has AM. Interventional workers have also reported
similar disappointing results with GDC coiling.27
Usually, we are firm advocates of early intervention
for aneurysmal SAH. However, in the presence of
AM, any intervention, whether surgical or endovas-
cular, may be deferred for weeks or months following
the onset of AM. Although the literature provides
scanty evidence to help in prognosticating in this
uncommon condition, the author believes that
delayed intervention may perhaps optimize the
chances of maximal spontaneous neurological im-
provement. Generally, the dismal prognosis carried
by the AM in presence of aneurysmal SAH makes
‘re-bleeding’ hardly a threatening consequence.
References
1 Cairns HWB OR, Pennybacker JB, Whitteridge D. Akinetic
mutism with an epidermoid cyst of the 3rd ventricle. Brain
1941;64:273 – 91.
2 Ackermann H, Ziegler W. Akinetic mutism—a review of the
literature. Fortschr Neurol Psychiat 1995;63:59 – 67.
3 Nemeth G, Hegedus K, Molnar L. Akinetic mutism associated
with bicingular lesions: clinicopathological and functional
anatomical correlates. Eur Arch Psychiat Neurol Sci
1988;237:218 – 22.
4 Buge A, Escourolle R, Rancurel G, Poisson M. Akinetic
mutism and bicingular softening. 3 anatomo-clinical cases. Rev
Neurol (Paris) 1975;131:121 – 31.
5 Nicolai J, van Putten MJ, Tavy DL. BIPLEDs in akinetic
mutism caused by bilateral anterior cerebral artery infarction.
Clin Neurophysiol 1726;112:1726 – 8.
6 Naito Y, Kuzuhara S, Yamanouchi H. Complete recovery
from akinetic mutism caused by bilateral thalamic infarction.
Rinsho Shinkeigaku Clin Neurol 1986;26:817 – 20.
7 Ueda A, Hirano T, Katsura K, et al. A case of juvenile cerebral
infarction caused by bilateral anterior cerebral artery dissec-
tion. Rinsho Shinkeigaku 2002;42:623 – 8.
8 Wolff V, Saint Maurice JP, Ducros A, Guichard JP, Woimant
F. Akinetic mutism and anterior bicerebral infarction due to
abnormal distribution of the anterior cerebral artery. Rev
Neurol (Paris) 2002;158:377 – 80.
9 Burruss JW, Chacko RC. Episodically remitting akinetic
mutism following subarachnoid hemorrhage. J Neuropsychiat
Clin Neurosci 1999;11:100 – 2.
10 Danilewicz B, Czepko R, Pyrich M, Betlej M, Stachura K,
Zawilinski J. Immediate and late results of surgical treatment of
hydrocephalus after subarachnoid hemorrhage. Przegl Lek
1990;47:678 – 81.
11 Hodozuka A, Takebayashi S, Nakai H, Hashizume K, Tanaka
T. A case of the syndrome of the sinking skin flap: case report.
No Shinkei Geka Neurol Surg 2000;28:245 – 9.
12 Jimbo M. Differential diagnosis of vegetative state and brain
death. Nippon Rinsho 1985;1:43160 – 3.
13 Hen R, Ito Z, Uemura K, Kawakami H. Cerebral hemody-
namics in the vegetative state patients – relationship between
patterns of dysautoregulation and prognosis (author’s transl).
No To Shinkei 1978;30:757 – 70.
14 Kanemoto Y, Tanaka Y, Nonaka M, Hironaka Y. Giant
aneurysm of the azygos anterior cerebral artery—case report.
Neurol Med Chir (Tokyo) 2000;40:472 – 5.
15 Koh CS, Inoue K, Kagaya H, Yanagisawa N, Tsukagoshi H. A
case of thrombosed giant basilar aneurysm associated with
akinetic mutism (author’s transl). Rinsho Shinkeigaku Clin
Neurol 1979;19:744 – 50.
16 Ogunyemi AO. Akinetic mutism caused by subarachnoid
haemorrhage. A case report. Centr Afr J Med 1984;30:273 – 4.
17 Nemeth G, Hegedus K, Molnar L. Akinetic mutism and
locked-in syndrome: the functional-anatomical basis for their
differentiation. Funct Neurol 1986;1:128 – 39.
18 Echiverri HC, Tatum WO, Merens TA, Coker SB. Akinetic
mutism: pharmacologic probe of the dopaminergic mesence-
phalofrontal activating system.PediatNeurol1988;4(4):228 – 30.
19 Hazouard E, Legras A, Corcia P, et al. Significance of single
photon emission computed tomography and akinetic mutism.
Rev Neurol (Paris) 1998;154:856 – 8.
20 Combarros O, Infante J, Berciano J. Akinetic mutism from
frontal lobe damage responding to levodopa. J Neurol
2000;247:568 – 9.
21 Watahiki Y, Narita S, Kurahashi K, Tanaka T, Matsunaga M.
Akinetic mutism from recurrent hydrocephalus: successful
treatment with levodopa, bromocriptine and trihexyphenidyl.
No To Shinkei 1987;39:977 – 82.
22 Caner H, Altinors N, Benli S, Calisaneller T, Albayrak A.
Akinetic mutism after fourth ventricle choroid plexus papillo-
ma: treatment with a dopamine agonist. Surg Neurol
1999;51:181 – 4.
23 Milhaud D, Bernardin G, Roger PM, Deloffre P, Corcelle P,
Mattei M. Treatment of akinetic mutism with bromocriptine.
Presse Med 1993;22:688.
24 Anderson B. Relief of akinetic mutism from obstructive
hydrocephalus using bromocriptine and ephedrine. Case
report. J Neurosurg 1992;76:152 – 5.
25 Stewart JT, Leadon M, Gonzalez-Rothi LJ. Treatment of a
case of akinetic mutism with bromocriptine. J Neuropsychiat
Clin Neurosci 1990;2:462 – 3.
26 Ross ED, Stewart RM. Akinetic mutism from hypothalamic
damage: successful treatment with dopamine agonists. Neurol-
ogy 1981;31:1435 – 9.
27 Ushikoshi S, Kikuchi Y, Houkin K, Miyasaka K, Abe H.
Aggravation of brainstem symptoms caused by a large superior
cerebellar artery aneurysm after embolization by Guglielmi
detachable coils—case report. Neurol Med Chir (Tokyo)
1999;39:524 – 9.
28 Kumral E, Bayulkem G, Evyapan D, Yunten N. Spectrum of
anterior cerebral artery territory infarction: clinical and MRI
findings. Eur J Neurol 2002;9:615 – 24.
Subarachnoid haemorrhage and akinetic mutism 257
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from
info
rmah
ealth
care
.com
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Uni
vers
itaet
s- u
nd L
ande
sbib
lioth
ek D
uess
eldo
rf o
n 11
/19/
13Fo
r pe
rson
al u
se o
nly.
29 Maurice-Williams RS. Delayed akinetic mutism after subar-
achnoid haemorrhage. Guys Hosp Rep 1972;121:229 – 31.
30 Oberndorfer S, Urbanits S, Lahrmann H, Kirschner H,
Kumpan W, Grisold W. Akinetic mutism caused by bilateral
infiltration of the fornix in a patient with astrocytoma. Eur J
Neurol 2002;9:311 – 3.
31 Rubin DI, So EL. Reversible akinetic mutism possibly induced
by baclofen. Pharmacother 1999;19:468 – 70.
32 Tutuncuoglu S, Kantar M, Tekgul H, Candan C. Akinetic
mutism due to diphenylhydantoin toxicity. Turk J Pediat
1997;39:403 – 7.
33 Assal G. Post-traumatic deficit syndromes. Schweiz Arch
Neurol Psychiat 1985;136:17 – 24.
34 Patricolo A, Chiapetta F, Esposito S, Gazzeri G. Hypothalamic
complications in the surgical treatment of aneurysms of the
anterior communicating artery. Minerva Neurochir
1971;15:146 – 50.
35 von Cramon D, Albus M. Bilateral anterior infarct and
hydrocephalus aresorptivus. Complications of a ruptured
aneurysm of the anterior communicating artery. Fortschr Med
1980;98:1602 – 6.
36 Nishigaya K, Kimura R, Naganuma H, Fukamachi A, Nukui
H, Kobayashi M. Ruptured cerebral aneurysm followed by
primary intracranial malignant lymphoma: case report. No
Shinkei Geka 1990;18:367 – 72.
37 Lechevalier B, Bertran F, Busson P, Chapon F, Raoul G, De
La Sayette V. Akinetic mutism with right hemiplegia caused by
infarction in the territory of the left anterior cerebral artery. Rev
Neurol (Paris) 1996;152:181 – 9.
258 K. A. Choudhari
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sbib
lioth
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eldo
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/19/
13Fo
r pe
rson
al u
se o
nly.