Neurorehabilitation and Neural
Repair
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Chronic Akinetic Mutism After Mesencephalic-Diencephalic Infarction: Remediated with
Dopaminergic Medications
Michael P. Alexander
Neurorehabil Neural Repair 2001 15: 151
DOI: 10.1177/154596830101500208
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Neurorehabilitation and Neural Repair 2001;15:151-156
© 2001 Demos Medical Publishing

Case Report

Chronic Akinetic Mutism After Mesencephalic-Diencephalic
Infarction: Remediated with Dopaminergic Medications
Michael P Alexander

Objective: Akinetic mutism (AKM) is an uncommon disorder with a complex
neuropathology. There is no generally accepted treatment, and it is not known if
late treatments are effective. The relationship between AKM and abulia is uncertain.
Methods: The effects of dopaminergic treatment of a patient with chronic AKM after
discrete bilateral infarctions of the mesencephalic ventral tegmental area and the lateral hypothalamus were studied with motor measures, the Functional Independence
Measure (FIM), and neuropsychological tests. Results: Treatment with a combination
of carbidopa/levodopa and pergolide produced prompt amelioration of AKM with dramatic and rapid improvement in FIM. An apathetic, amotivational state persisted despite resolution of akinesia and normal frontal executive functions. Conclusions: AKM
may respond to dopaminergic treatment even after months of severe akinesia. The

mechanism of abulia is more complex than simply a partial dopaminergic deficiency
state and may persist even when AKM is treated and frontal cognitive functions are
normal. Key Words: Akinetic mutism—Dopamine—Abulia.

Akinetic mutism (AKM) is an uncommon neurologic condition characterized by paucity and slowness of
movement and speech despite retamed capacity to move
and to speak (1). Although the pathologic anatomy of
AKM has been identified, many diseases that may cause
it are known, and some treatments have been reported,
several aspects of AKM are not optimally clarified (2).
The clinical recognition of AKM is not always straightforward. When there is also paresis, the contribution of

From Memory Disorders Research Center, Boston University Department of Neurology, and Departments of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massa-

chusetts
Presented m part at the American Academy of Neurology, Seattle,
May 1995.
Address correspondence and reprmt requests to Michael P Alexander, M D., Behavioral Neurology Unit, Beth Israel Deaconess Medical
Center, 330 Brooklme Avenue, Boston, MA 02215, U.S.A.

akmesia to disability may not be recognized. Potential
markers for specific treatments have not been established,
nor is it clear whether chronic AKM responds to treatment. It has been suggested that the amotivational state

(abulia) that sometimes accompanies frontal lobe damage is a lesser form of AKM (2), but it is unknown
whether they necessarily have the same pathophysiology.
If abulia represents lesser injury to the same neural system as AKM, they might have a common treatment.

Case Report
This 36-year-old, right-handed, college-educated
had a stepwise neurologic deficit that progressed
over 15 days. History is significant only for infrequent
common migrame headaches and two normal term pregnancies. Her only medication was an oral contraceptive
woman

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that she had been using for 2 years. After 3 days of se-

headache, she collapsed at home, was bmefly unresponse, and was admitted to the hospital. She was alert,
vere

cognitively mtact, but had left lower facial weakness.
EEG, unenhanced computed tomography (CT), and lumbar puncture were normal. The next day she was less responsive but otherwise unchanged. Magnetic resonance
imaging (MRI) demonstrated bilateral paramedian mid,
brain-thalamic infarcts. Magnetic resonance angtography (MRA) suggested a narrowed distal basilar artery.
Complete coagulation profile, transthoracic echocardiogram, chest radiograph, mammogram, and pelvic ultrasound were normal. Over the next 2 days, she became
drowsier, and vertical gaze paresis and left-sided weakness
developed. Conventional arteriography demonstrated
narrowing of the midbasilar and no filling m the distal
basilar. Heparin was begun. For 6 days, she showed rapid
improvement. On day 14, she again became lethargic
with worsened left hemiparesis. MRI demonstrated a new,
left pontme infarct. Repeated conventional arteriography showed increased narrowing of the basilar artery. She
remamed minimally responsive. On day 32, a right temporal bram/meningeal biopsy was negative. A feeding
tube was placed, and she was discharged to a rehabilitation hospital 40 days after the initial symptoms.
On admission to rehabilitation, she was described as
mute, lying in bed m essentially decorticate posture, with

She was bed-bound and dependent m all
She underwent 3.5 months of daily mtense multi-

no movement.
care.

disciplinary therapy. Relaxation, neuromuscular reeducation, passive ranging, serial casting to all four limbs, re-

peated phenol blocks, and trials of diazepam (up to 15 mg,
t.i.d.), dantrolene (up to 125 mg, qd), and baclofen (Lioresal ; up to 30 mg, t.i.d.) produced little change m function. Vigorous attention to positioning improved swallowmg, and the g-tube was removed after 3 months. At
discharge (5 months after onset), she still had minimal
speech and movement. Medications were dantrolene, 25
mg qd; baclofen, 20 mg, b.i.d.; and oxycodone with acetaminophen (Percocet; 1-4 qd) for limb pam.
At home she required daily services for self-care, suspension transfers, and positioning. Six days weekly, she
had 3 h of outpatient therapy. Treatment contmued to
focus on relaxation, maintenance of range, positioning,
and strengthening. She had botulmum treatments at the
left hand and wrist and left ankle with modest results.
Dantrolene and baclofen were increased with no improvement but with decreased responsmeness.
She was admitted to a second rehabilitation hospital
m hope of identifymg interventions that would allow less
mtense home services. She had almost no spontaneous
speech and very terse responses to questions, with response
latencies routinely >20 s. Speech was aprosodic and hy-

pophonic. Allowing for her extremely slow responses, language and memory seemed normal. Visual fields and pupillary size and responses were normal. All pursmt and hornzontal saccadic eye movements were normal, but she could
produce no vertical saccadic movements. Vertical doll’seyes responses were present. She had moderate lid retraction, very reduced blink rate (<1/mm), and very exaggerated glabellar response. She had masked facies and left
lower facial weakness to command. There was low-amplitude titubation. She was generally akmetic, particularly on
the left, and tended to rest in bed or chair m a near-decorticate position. When prompted, she had good power on
the right, although all requested movements were delayed
and had reduced amplitude, with a coarse proximal tremor.
She required 29 min to do 10 fmger-to-nose circuits at a
distance of 30 cm. She could isolate all small-finger movements, although she required much prompting to continue.
Power m the left leg was good, although agam delayed and
also with a significant action dystoma. The left arm was
fisted m decorticate position with decreased passive range
at all omts. Sensation was normal. Tendon reflexes were
brisk and equal; both toes went down.
Her functional status on admission after 6.5 months
of intense therapy (-600-700 h) was still limited. She
transferred from bed to chair with maximal assistance.
She sat with maximal assistance for support and stood
with moderate assistance using the left ankle-foot orthosis (AFO), but she had no postural reflexes and could
not ambulate or advance her wheelchair. She could do
feeding, grooming, and oral hygiene with maximal assistance ; all other self-care was dependent. Speech mtelligibility was poor: 32% at sentence level. Her overall
Functional Independence Measure (FIM) was 42 (3).
Standard rehabilitation mterventions were contmued,
and carbidopa/levodopa was begun at 10/100 b.i.d. Within
days her movement and speech began to improve. She was
mcreased to a daily dose of 60/600 over 2 weeks. Pergolide
was begun 0.05 mg, b.i.d.. Dantrolene was stopped widthout any clmcal change. Speech latencies were < 10 s; mtelligibility at sentence level had improved to 55%. Titubation and right arm tremor were reduced. Speed of
movement increased; 10 cycles of finger-to-nose, as previously described, required 16 s (45% faster). She sat mdependently and stood with supervision, no AFO required,
although postural stability was still poor. She advanced her
wheelchair mdependently and walked 150 feet with a
rolling walker with minimal assistance. Her upper body
self-care required at most supervision, and lower body,
moderate assistance. Her overall FIM was now 87. She was
transferred to a subacute facility for further therapy.
Four weeks later, taking carbidopa/levodopa 60/600
daily m five doses, and pergolide, 0.10 t.i.d., spontaneous
movement and speech were much more frequent. Re-

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Magnetic resonance imaging performed several months after onset: T, study (A; 2-mm slices and 1-mm gap) demon(a) the left pons, basis, and tegmentum; (b) bilateral midbram (upper center and lower left scans); (c) bilateral hypothalamus; and (d) the right thalamus, partly paramedian and partly in dorsomedial nucleus. Detail from T2 coronal study
(B) demonstrates the right thalamic infarction and also demonstrates the hypothalamic lesions medial and anterior to red nucleus

Figure 1.

strates mfarctions in

and substantia nigra.

sponse latencies were near normal. Voice volume and m-

telligibility were normal although still aprosodic. She ambulated mdependently, ate, and did most self-care mdependently. She went home to live with her family with
minimal home services.
Over the next 8 months, the three medications were
systematically adjusted. Increasing baclofen to 20 mg,

q.i.d., produced no improvements m her persistently tight
left arm. Decreasing it to 10 mg, b.i.d., produced mcreased gait mstability because of left-ankle action dystonia and clonus. Reduction of carbidopa/levodopa to
25/100, b.i.d., quickly produced worsening akmesia, postural mstability, and increased tremor. At pergolide, 0.30
t.i.d., and carbidopa/levodopa, 25/100 five times daily,
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she ambulated completely independently without any assistive device. She was essentially mdependent m selfcare, more talkatme, and doing some household chores.
Her family noted that she appeared unmotivated to mcrease her independence.
She was lost to follow-up for 11 months. Her family
brought her for reevaluation because of her apathy and
poor motivation. Dosages of medications had not been
changed. Examination was unchanged. Increasing either
pergolide or carbidopa/levodopa caused orthostatic hypotension. When either was reduced, tremors and balance worsened. Fluoxetme was added at 10 mg qd with
no effect. After it was mcreased to 20 mg qd, her motivation to do home activities seemed better, but she also
had a marked increase m irritability. The dose was reduced to 10 mg qd. At last follow-up, she had not at-

tempted any return to employment. She expressed little
mterest m household activities, in mcreasmg her role m
her family, doing the home activities that she is able to
do, or pursuing any leisure activities. She often simply sits
for hours.

Neuropsychological Assessments
At 7 months after onset, she was onented, had normal nammg and repetition, normal praxis, and normal
delayed recall of a four-word list. Performance was qmte
delayed, and she often required multiple prompts to produce any response. Because of severe akmesia and
mutism, formal testmg was not possible before treatment.
Her first comprehensive evaluation was 13 months after
onset. Language, fund of knowledge, verbal subtests of
the WAIS-R, Wisconsin Card Sort, Raven’s Progressive
Matrices, and verbal fluency were entirely normal.
Follow-up evaluation (28 months after onset)
demonstrated little change, although some time-dependent tasks were faster. The Stroop test was normal.
Word-list generation (FAS) was average. List learning
was mildly impaired (7-11-14-14-13), but semantic clustering was used as a learning strategy. Delayed recall
(12) was slightly low, but recognition was normal (16 of

16).
At the final neuropsychological evaluation at 39
months after onset, results were essentially normal. She
remained slow on some tasks, especially perceptual-motor
tasks. She had material-specific memory deficits for visual
nonverbal material. All executive cognitive tasks were
normal. The patient was, however, quite aware of, and her
family complamed of, her lack of mterests and poor motivation. She demed any depression, and there were no
vegetative symptoms of depression. Her manner was jocular and breezy.

Discussion
AKM is a disorder m activation to move and to

speak despite conscious awareness, perhaps even the &dquo;desire&dquo; to speak or move, and no impairment m power, coordination, or tone that restricts movement (1). AKM
has been reported as a consequence of lesions m numerous bram regions: (a) bilateral medial frontal (4-7), even
when restricted to anterior cmgulate gyn (ACG) (8-10);
(b) the anterior hypothalamus (11,12) (usually tumors);
(c) with acquired hydrocephalus (13-17); (d) severe diffuse axonal injury of trauma (durmg recovery) (18,19);
(e) bilateral globus pallidus (20-22); (f) the paramedian

mesencephalic-diencephalic region (usually infarctions)
(23-28).
Lesions in any of these areas can damage part of a
neural system critical for activating movement (including
speech) and probably cogmtion without affectmg the patterns or content of either. Damage directly to dopammergic neurons m the midbram or to their ascendmg projections may be the most common pathophysiology of
AKM. There is substantial overlap in the midbram of the
dopammergic neurons projecting to stnatum and those
projecting to cortex (29), but the cortical projections are
more medial and dorsal than the stnatal; that is, they are
centered m the ventral tegmental area (VTA) (30). This
mesocortical system projects through the medial forebram
bundle (MFB) (31 ). The MFB runs through the lateral
hypothalamus into the septal area and then into the infraventricular white matter before projecting to the ACG
and other, predommantly medial frontal structures (32).
MFB pathways are strictly uncrossed (29). Lesions m the
nonnigral ventral tegmental area (VTA, region A10)
cause dopamine depletion m frontal cortex only, and damage to the MFB produces akinesia (31 ).
The terminations of the mesocortical pathway m
frontal lobes are pnmanly the supplementary motor area
(SMA) and the ACG, and bilateral damage to the ACG
and SMA produces AKM. ACG and SMA share many
connectivity properties (33, 34). In addition to the
dopaminergic afferents from the VTA (29), both have bilateral efferents to frontal and premotor cortex and major
projections to the stnatum (33, 34) running in the
periventricular white matter (35). Damage to medial
frontal cortex or to its deep projections produces impaired
activation. Unless very extensive, even bilateral SMA and
ACG damage does not typically cause severe global akinesia, but m some cases, the clmcal presentation can be
to that of the midbrain lesions (36).
quite similar

clinically
Dopaminergic inputs to the stnatum arise from more
lateral midbram structures, primarily the zona compacta
of the substantia nigra (29, 37), and pass through the ventral posterior limb mternal capsule (30). Damage re-

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stncted to the cells of origin produces profound akinesia
(37). The stnatum projects to the globus pallidus. Damage to the globus pallidus produces severe akinesia (38),
and stimulation of globus pallidus can elimmate akmesia (39). Much of the mternal segment of the globus pallidus output is to the thalamus: VA, VL, and CM nuclei,
and the IL region. Damage to the pallidothalamic pathways as they cross the ventral mternal capsule or m the
mtramedullary thalamus may also produce akinesia (40).
The ascending systems are strictly uncrossed. The
cortical efferents are bilaterally distributed. The pallidal
efferents are uncrossed. Complete AKM requires bilateral lesions, although they need not be symmetrical. In
this case, damage was asymmetrical. The precise basis is
uncertam but mcludes at least the right VTA, ascendmg dopammergic pathways m the left lateral hypothalamus, and the medial pallidothalamic pathways.
That AKM responds to vanous medications has also
been known for years (41). L-DOPA, bromocriptme,
lisuride, metoprolol, methylphenidate, and amphetamine

have all been used, but the best agents, optimal doses,
and duration of treatment are unknown. Successful treatment has been reported m TBI (18, 42), herpes simplex
encephalitis (43), hydrocephalus after ventricular shunt
failures ( 13, 14, 16, 17 ), basal tumors (12), hypoxia (42),
and various causes of chronic hepatic encephalopathy
(44). Bromocnptme is the most commonly reported
agent. Once successfully treated, sensitivity to dose reduction has been variables. Given the remarkable number of possible lesions within a very small anatomic region that can cause AKM, it is not surprising that drug
treatment has had variable results. Damage to the afferent (dopammergic) system should be preferentially responsive to dopa agents.
In this case, AKM was not clmically recogmzed for
8 months after onset, perhaps because left hemiparesis developed at the same time. Two features of the examination might have suggested coexistent AKM. First, preservation of isolated finger movements, even with long delay
after requested movement, is atypical m corticospmal
pattern paresis. Second, loss of vertical gaze pomts to a
paramedian injury that often produces AKM. Although
the initial dose was low and peripheral dopamme metabolism was surely not blocked at the starting doses, a
striking clmcal response was seen within days of starting carbidopa/levodopa after months of unchangmg
deficit. Additional benefit was seen with pergolide. In
this case, treatment will probably be permanently required, as attempts to decrease either drug caused worsened deficits within days. Dopaminergic treatment should
be considered even in very chronic cases of AKM.
Despite excellent motor recovery with treatment and
no evidence of executive cognitive deficits, she has re-

mained apathetic and emotionally mdifferent (i.e., abulic). The lack of response of the motivational deficits
under dopammergic treatment suggests that abulia need
not be simply a milder form of AKM. It is still possible
that dopamine deficiency does underlie both disorders,
but that the motor-response impairment (AKM) is more
directly mediated by dopamine and, thus, more directly
treated with dopammergic agents. A similar observation
of differential response to treatment has been made in
cognitive functions (45). In a group of patients with cognitive impairments, but not AKM, after traumatic bram
injury, bromocnptme improved a subset of executive
functions but did not affect working memory, an allegedly
dopamme-dependent operation (46). Various cognitive,
motor, and emotional capacities may share a requirement
for ascending dopammergic input but remain anatomically segregated, use different dopamme receptor systems,
or differ m the extent of direct modulation by dopamme.
In this patient, it can be concluded that abulia is not due
to a simple dopamme deficiency and is not just part of
AKM, as the latter improved so dramatically, and the former not at all. It is also not due to a general executivesystem impairment, as standard assessments of executive
cognitive functions are mtact. Apathy is likely a very
complex disorder with cognitive, emotional, visceral, and
activational components (9). If they have an effect,
dopammergic agents may treat only the activational
component. Perhaps in this patient, the lesion in the
right antenor thalamus has disrupted the emotional components and is the source of the persistent apathy.

Acknowledgment
Supported in part by program project grant NS
26985 to the Boston University School of Medicme,
Memory Disorders Research Center.

References
1

2
3

4

5

6

Alexander MP Disturbances in language initiation mutism and
its lesser forms In Young R, Josephs AB, eds Movement disorders
m neurology and neuropsychiatry Oxford. Blackwell, 1992.389-96.
Fisher CM Honored guest presentation abulia minor vs agitated
behavior Clin Neurosurg 1985;31.9-31.
Stmeman MG, Escarce JJ, Gom JE, Hamilton BB, Granger CV,
Williams SV. A case mix classification system for medical rehabilitation Med Care 1994;32:366-79.
Ferbert A, Thron A Bilateral anterior cerebral atery territory mfarction in the differential diagnosis of basilar artery occlusionJ
Neurol 1992;239:162-4.
Laplane D, Talaraich J, Meininger V, Bancaud J, Orgogozo JM
Clinical consenquences of coticectomeis involving the supplementary motor area in man. J Neurol Sci 1977;34 301-14.
Lechevalier B, Bertran F, Busson P, Chapon F, Raoul G, De
La Sayette V (Akmetic mutism with right hemiplegia caused by
155

Downloaded from nnr.sagepub.com at Utah State University on September 27, 2014

infarction m the territory of the left anterior cerebral artery). Rev
Neurol ),
Pans 1996,152.181-9.
(
7. Minagar A, David NJ. Bilateral infarction m the terntory of the
anterior cerebral arteries (see comments). Neurology 1999,52:
886-8.
8. Barns RW, Schuman HR. Bilateral anterior cingulate lesions syndrome of the anterior cingulate gyn Neurology 1953,3 44-52.
9 Devinsky O, Morrell MJ, Vogt BA. Contributions of the anterior
cingulate cortex to behavior Brain 1995,118.279-306.
10. Nielsen JM, Jacobs LL Bilateral lesions of the anterior cingulate
gyri. Bull LA Neurol Soc 1951;6:231-4
11 Cairns H,Oldfield RC, Pennybacker JB, Whitteridge D. Akinetic
mutism with an epidermoid cyst of the third ventncle Brain

1941;64:273-90.
12. Ross ED, Stewart RM. Akmetic mutism from hypothalamic damage. successful treatment with dopamine agonists

Neurology

the mesencephalon and diencephalon Arch Neurol 1987,44
1127-33
27. Robles A, Aldrey JM, Rodriguez Fernandez RM, et al. (Paramedian bithalamic infarct syndrome report of five new cases). Rev
, 1995,23 276-84.
Neurol
28. Segarra JM. Cerebral vascular disease and behavior, I. the syndrome of the mesencephalic artery (basilar artery bifurcation)
in

Arch Neurol
1970,22:408-18.
Fallon JH. Topographic organization of ascending dopaminergic
projections Ann N Y Acad Sci 1988;537:1-9.
30. Ungerstedt U Stereotaxic mapping of the monoamine pathways
m the rat brain. Acta Physiol Scand Suppl 1971,367.1-48
31. Lmdvall O, Bjorklund A, Moore RY, Stenevi U. Mesencephalic
dopamine neurons projecting to neocortex Brain Res 1974,81
325-31.
32 Nauta WHJ, Feirtag M Fundamental neuroanatomy
. New York
29

1981,31.1435-9

WH Freeman, 1986

13. Anderson B. Relief of akmetic mutism from obstructive hydrocephalus using bromocriptine and ephedrine: case report J Neuro-

33

surg 1992;76.152-5

14

1980,103:525-54

Berger L, Gauthier S, Leblanc R Akinetic mutism and parkin-

associated with obstructive hydrocephalus. Can J Neurosci
1985,12 255-8
15. Moser A, Freyberger HJ, Bruckmann H, Kompf D. Akinetischer

34. Jurgens U. The efferent and afferent connections of the supplementary motor area. Bram Res 1984;300.63-81

sonism

mutismus bei

16.

17.

18.

19

20.

dekompensiertem triventrikularen hudrozephalus.
Fortschr Neurol Psycbaitr 1995,63.248-51
Aidi S, Elalaom-Faris M, Benabdeljlil M, Benomar A, Chaoui
M, Chkili T Akinetic mutism and progressive supranuclear palsylike syndrome after the shunt of an obstructive hydrocephalus:
successful treatment with bromocriptine 2 cases. Rev Neurol
Pans 2000;56. 380-3.
(
)
Caner H, Altmors N, Benli S, Calisaneller T, Albayrak A. Akinetic mutism after fourth ventncle choroid plexus papilloma:
treatment with a dopamine agonist. 1999;51:181-4.
Surg Neurol
Crismon ML, Childs A, Wilcox RE, Barrow N The effect of
bromocriptine on speech dysfunction m patients with diffuse brain
injury (akinetic mutism). Clin Neuropharmacol 1988,11.462-6.
Levm HS, Madison CF, Bailey CB, Meyers CA, Eisenberg HM,
Gumto FC. Mutism after closed head injury Arch Neurol 1983;
40.601-6
Laplane D, Baulac M, Widlocher D, Dubois B. Pure psychic akinesia with bilateral lesions of basal ganglia. J Neurol Neurosurg

Psychiatry 1984,47:377-85
21.

22.

23.

24

25.
26.

Baleydier C, Mauguiere F The duality of the cingulate gyrus in
monkey. Neuroanatomical study and functional hypothesis Bram

35. Yakolev PL, Locke S. Limbic nuclei of the thalamus and connections of limbic cortex. Arch Neurol 1961;5.364-400
36. Borggreve F, De Deyn PP, Marien P, Cras P, Dierckx RA Bilateral infarction in the anterior cerebral artery vascular territory due
to an unusual anomaly of the circle of Willis (see comments)
Stroke 1994;25:1279-81.
37. Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM,
Kopm IJ. A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra

38.

J Neurophysiol 1984,52:290-304.
Iacono RP, Lonser RR, Mandybur G, Yamada S. Stimulation of
the globus pallidus in Parkinson’s disease. Br J Neurosurg
1995,9.505-10
40. Kuo JS, Carpenter MB Organization of pallidothalamic projections in the rhesus monkey. J Comp Neurol
1973,151 201-36.
41. Daley DD, Love JG. Akinetic mutism Neurology 1958,8:238-42.
42 Muller U, von Cramon DY The therapeutic potential of
39.

Mega MS, Cohenour RC. Akinetic mutism: disconnection of
frontal-subcortical circuits. Neuropsychiatry Neuropsychol Behav
Neurol 1997,10.254-9.
Ure J,Faccio E, Videla H, et al Akinetic mutism: a report of three
cases. Acta Neurol Scand 1998,98.439-44.
Botez MI, Barbeau A Role of subcortical structures, and particularly of the thalamus, m the mechanisms of speech and language
a review. 1971
Int J Neurol 8.300-20
Castaigne P, Lhermitte F, Buge A, Escourolle R, Hauw JJ, LyonCaen O. Paramedian thalamic and midbram infarct. clinical and
, 1981;10.127-48.
neuropathological study Ann Neurol
Guberman A, Stuss D. The syndrome of bilateral paramedian
thalamic infarction. Neurology 1983;33.540-6.
Katz DI, Alexander MP, Mandell AM Dementia following strokes

by N-methyl-4- phenyl-1,2,3,6-tetrahydropyridine

Proc Natl Acad Sci U S A 1983;80.4546-50
Horak FB, Anderson ME. Influence of globus pallidus on arm
movements in monkeys, I effects of kainic acid-induced lesions

bromocriptine in neuropsychological rehabilitation of patients
with acquired brain damage. Prog Neuropsychopharmacol Biol Psychiatry 1994,18 1103-20.
Milhaud D, Bernardin G, Roger PM, Deloffre P, Corcelle P, Mattei M. Treatment of akinetic mutism with bromocriptine [Letter]. Presse Med 1993,22.688.
44 Barrett K Treating organic abulia with bromocriptine and lisuride:
four case studies. J Neurol Neurosurg Psychiatry 1991,54. 718-21.
45. McDowell S, Whyte J, D’Esposito M. Differential effects of a
dopaminergic agonist on prefrontal function in traumatic brain
injury patients. Brain 1998; 121.1155-64.
46. Sawaguchi T, Goldman-Rakic PS. D1 dopamine receptors in prefrontal cortex: involvement in working memory Science 1991,
251:947-50
43.

156

Downloaded from nnr.sagepub.com at Utah State University on September 27, 2014