akinetic mutism following stroke

Journal of Clinical Neuroscience (2004) 11(1), 25–30

0967-5868/$ - see front matter ª 2003 Elsevier Ltd. All rights reserved.

doi:10.1016/j.jocn.2003.04.002

Clinical study

Akinetic mutism following stroke

Nages Nagaratnam, Kujan Nagaratnam, Kevin Ng, Patrick Diu

Blacktown-Mount Druitt Health, Blacktown, NSW 2148, Australia

Summary This is an appraisal of the varied clinical presentation and the neural substrate for akinetic mutism following stroke. The diagnosis is

important as akinetic mutism is often misdiagnosed as depression, delirium and locked-in-syndrome.This is a descriptive study of eight selected

patients with akinetic mutism following infarction/haemorrhage in different regions of the brain with characteristic syndromes. They involved the

critical areas namely, the frontal (cingulate gyrus, supplementary motor area and dorso-lateral border zone), basal ganglia (caudate, putamen),

the mesencephalon and thalamus. The disorders of speech and communication took different forms. The speech disorder included verbal

inertia, hypophonia, perseveration, softened and at times slurred. The linguistic disturbances were fluent, non-fluent, anomia and transcortical

(motor, mixed) aphasias. The findings were related to what is known about the neuroanatomic location of the lesions and the role of the frontal-

subcortical circuitry in relation to behaviour. Akinetic mutism could be explained by damage to the frontal lobe and or interruption of the complex

frontal subcortical circuits.

ª 2003 Elsevier Ltd. All rights reserved.

Keywords: akinetic mutism, abulia, apathy, aphasia, stroke, frontal subcortical circuitry

INTRODUCTION

Akinetic mutism (AM), abulia and apathy are terms that have beenused to describe behavioural abnormalities relating to reducedactivity and slowness. Several investigators proposed that theseclinical states are simply a continuum of severity of reduced be-haviour and AM may be an extreme form.1

Following the landmark case report of Cairns et al.,2 the termAM had been used to describe a syndrome characterised bymarked reduction of nearly all motor functions including facialexpression, gestures and speech output but with some degree ofalertness. They described a patient with an epidermoid cyst in thethird ventricle whom after several evacuations of the cyst becamemore alert and responsive. Since then AM had been used in sit-uations with similar clinical picture associated with differentaetiologies and pathologies. There is considerable variation in thepresentation of such patients and the clinical features of AMcorrespond more closely to the functional anatomy of the brainregions affected rather to the pathology.

This paper will appraise (i) stroke patients with AM selected toillustrate the variability in the clinical presentation, speech andlanguage characteristics and course of the disease process and (ii)the likely pathophysiological mechanisms that underlie the di-verse locations associated with AM.

ILLUSTRATIVE CASES

Right supplementary area and cingulate gyrus

A 77-year-old right handed woman was seen with left-sidedhemiplegia on day two. She was drowsy and responded poorly toverbal commands. She had a right gaze palsy with total weaknessof the left arm and leg. The tone was decreased and the left plantarwas extensor. She was in atrial fibrillation. On day 8 she was alertand non-communicative but seemed to comprehend. Three weekslater although she was alert, she was markedly akinetic with no

Received 17 October 2002

Accepted 9 April 2003

Correspondence to: Nages Nagaratnam, Blacktown-Mount Druitt Health,

Blacktown, NSW 2148, Australia.

speech output except for an occasional word. There was somereturn of power to the left arm. There was no grasp reflex orforced grasping. The CT scan of the brain done on day 2 showedan infarction in the territory of the right anterior cerebral artery(Fig. 1). When seen four weeks post-onset she remained mute.

Left supplementary motor area cingulate gyrus andpremotor area

A 75-year-old right handed man was seen in hospital with a right-sided hemiparesis and inability to talk. He was alert and hadweakness of his right arm and leg, leg more than arm (subtle). Thetone was increased in all four limbs. He had a grasp reflex withforced grasping. He spoke with an occasional “yes” and the voicewas of low volume and showed no emotion. The findings of thespeech assessments at two weeks and a month later were that of ananomic aphasia (Table 1). The CT scan demonstrated an infarctionin the left anterior cerebral artery territory involving the sensory,motor, supplementary motor area, prefrontal and anterior part ofthe cingulate gyrus (Fig. 2).

Right cingulate gyrus and deep left parietal

A right-handed 38-year-old male was seen with right-sidedweakness. The CT scan done the following day and a repeat scanfour days later did not reveal any abnormality. He suffered fromdysarthria and at the end of 4 weeks he had largely recovered andwas walking independently. Cerebral angiogram was normal sowas the carotid doppler. Investigations such as echocardiogram,cardiolipin antibodies, procoagulants, ANA, and ds DNA were allnormal. He was seen 10 months later with a recurrence of hisright-sided weakness. The CT scan and MRI showed hypodenseareas abutting the corpus callosum and involving the cingulategyrus on the right side and deep in the left parietal region (Fig. 3).Speech output was markedly reduced and whatever words he ut-tered were slurred. Comprehension was possible. He had right-sided weakness and bilateral plantar responses. When seen a weeklater he was alert but had reduced verbal output. Comprehensionwas relatively unimpaired and was able to identify objects, col-ours, geometric designs, letters and body parts. The voice washypophonic. He remained alert with eyes open and tracking with

25

Fig. 1 CT scan showing infarction in the right anterior cerebral artery territory.

Table 1 Results of the Western Aphasia Battery test

19.04.98 15.5.98

Spontaneous speech Severe impairment

Information content (10) 0 8

Fluency (10) 0 9

Comprehension Moderate impairment

Yes/no questions (60) 39 59

Auditory word recognition (60) 32 54

Sequential commands (80) 16 72

Repetition (100) Severe 2 96

Naming Severe impairment

Object naming (60) 0 60

Word fluency (20) 0 8

Sentence sequence (10) 4 10

Responsive speech (10) 0 10

Aphasia quotient 9.4 89.3

Reading and writing were severely impaired initially and reassessment.

( ) Maximum score.

26 Nagaratnam et al.

generalised slowness but able to communicate, though poorly. Hedied suddenly two weeks later and no autopsy was done.

Caudate nucleus

A right handed 72-year-old English speaking man of Polish ex-traction was seen in hospital for not talking over three days withnumbness and weakness of his right side of less than a day. He had


been well till three days earlier when the wife noticed him sittingand apparently in “deep thought” and never spoke. Two days laterhe had weakness of the right arm and was unsteady on his feet.These symptoms had largely resolved by the time he was seen inhospital. He was a hypertensive. On examination he was alert. Thespeech output was markedly reduced and expression was limitedto single words when actively spoken to. An Aphasia LanguagePerformance Scale was completed but detailed aphasia assessmentwas not possible. The rest of the nervous system was normal. TheCT scan of the brain showed a hypodense area in the region of theleft caudate nucleus (Fig. 4).

Putamen

This case had been reported in detail earlier.3 This is a 79-year-oldman who was seen with slurred speech and had difficulty inproviding responses to questions with prolonged delay. His voli-tional swallowing was slow chewing was effortful and keptremnants of food in the mouth. He had subtle weakness of hisright side but could walk only with two people. On the BostonDiagnostic Aphasia Examination he was slow with longer in-structions, correct naming of objects and expression were 75%and 50%, respectively, with perseveration on previous response.The findings were consistent with abulia and this lasted for morethan 12 weeks. The CT scan done on day 1 revealed an extensivehaemorrhage in the region of the left putamen and extending to-wards the internal capsule. On day 18 a repeat CT scan showed a


Fig. 2 CT scan showing in the territory of the left anterior cerebral artery involving the sensory, motor, supplementary motor area, prefrontal and anterior part o

the cingulate gyrus.

Fig. 3 MRI scan showing hypodense areas abutting the corpus callosum and involving the cingulate gyrus on the right side and deep in the left parietal region.

Akinetic mutism following stroke 27

hypodense area in the left putamen. On day 60 proton-density-weighted image demonstrated haemosiderin rim in the externalcapsule and a slit extending towards the thalamus (Fig. 5).

Border zones

A 73-year-old man had combined coronary artery bypass and rightcarotid endarterectomy. He had subtle residual weakness on theleft side following an earlier stroke. Post-operatively, he went intocardiogenic shock. Two days later he was alert but was unable tospeak with weakness of the left arm and leg and reluctant to movehis limbs. The tone was increased in all four limbs but the reflexeswere normal. The plantars could not be elicited. Finger dexteritywas poor bilaterally.

He could hardly talk and that to in single words when ac-tively spoke to with a low voice, he understood what was said.

ª 2003 Elsevier Ltd. All rights reserved. Journal of Clinical Neuroscience (2004) 11(1), 25–30

f

However, he was slow and reluctant to carry out simple verbalcommands. The speech output over the next two weeks re-mained markedly reduced, hypophonic and slurred with a ten-dency to perseverate and hardly exhibited any emotion. He hada grasp reflex in his right hand but no forced grasping. Eightweeks post-onset speech assessment revealed the expression tobe restricted but able to produce personal information reason-ably accurately and repetition skills were good and was able toidentify object functions. Yes/no responses were unreliable andwas able to follow commands at the two-word level. A weeklater the speech output was somewhat improved and showedmore emotion and was able to stand and walk with minimalassistance.

The CT scan of the brain showed hypodense areas at the levelsof the centrum semiovale and corona radiata in the central borderzones (right) and in the cortical border zones dorsolateral (left)

Fig. 4 CT scan showing a hypodense area in the region of the left caudate

nucleus.

Fig. 5 On MRI a proton-density-weighted image demonstrating

haemosiderin rim in the external capsule and a slit extending towards the

thalamus.


and posterolateral (right) consistent with bilateral watershed in-farctions (Fig. 6).

Thalamus

A 50-year-old right-handed man and a known hypertensive wasadmitted with left-sided weakness, gaze palsy and was mute.There was apathy with limited responses after long delay. The CTscan of the brain showed a primary right thalamic haemorrhage.On day 3 he developed haemocephalus with mass effect and anexternal ventricular drain was inserted. He remained mute forseveral days with return of speech which was slow, hypophonicand slurred. His mood fluctuated, he was impulsive with denial.

Mesencephalothalamic

A 64-year-old right handed man following a left thalamo-me-sencephalic infarction lacked spontaniety with perseveration ofmovements had been described in an earlier article written by theauthor.4 The CT scan demonstrated an infarction in the regions of


the left thalamus and midbrain bilaterally. Over the next threemonths he remained hypokinetic and his ability to communicatefluctuated from reduced speech to mutism and hypophonia. Healso exhibited disinhibition, incontinence and gait dyspraxiasuggestive of frontal lobe dysfunction. His language deficitsfluctuated with impairment of comprehension, non-fluency, ano-mia with retention of the ability to repeat and the findings wereconsistent with mixed transcortical aphasia.

Table 2 summarises the neurological, neurobehavioural andradiological findings. None of the patients in this study had do-pamine agonists.

DISCUSSION

Eight patients with AM involving different anatomical sites and ofmaximal importance the frontal lobe (supplementary motor area,cingulate gyrus), basal ganglia (caudate, putamen/globus pallidus)and the mesencephalothalamic regions were selected for consid-eration. The diagnosis of AM requires certain criteria for this isnot only important scientifically but also for use in clinicalpractice and in research. Furthermore the heterogeneity among thepatients with akinetic mutism may raise the possibility of suchvaried conditions as advanced Alzheimer’s Disease, Pick’s Dis-ease, Creutzfeld-Jakob’s Disease and may complicate certainpsychiatric disorders including catatonic schizophrenia, severedepression or conversion reaction. AM is erroneously diagnosedas depression, delirium or locked-in-syndrome which are not un-commonly associated with stroke. Depression is a significantproblem in stroke patients. The blunted emotional expression to-gether with apathy and in some patients psychomotor retardationsuch as slurring of speech and body movements may mimic AM.Distinguishing between them is important as treatment differs. Inlocked-in-syndrome the patient is awake and aware but is unableto communicate due to paralysis in all parts of the body but for eyemovements and this is the only way he can communicate. It arisesfrom a lesion in the basis pontis with involvement of the spinaland corticobulbar tracts. Case 3 in this study may be mistaken forlocked-in-syndrome. The pathologies in AM have ranged frommeningitis, encephalitis, hydrocephalus, trauma, tumours, thirdventricular cysts to vascular lesions namely ruptured aneurysmsand infarction. Depending on the clinical picture AM had beensubdivided into two types based on the anatomical location of thelesion. One is related to the mesencephalic region and described as“apathetic” akinetic mutism or “somnolent” mutism. The other isknow as “hyperpathic” akinetic mutism and is associated withbilateral frontal damage.5 In the mesodiencephalic regions therehas been several reports of AM resulting form circulatory dis-turbances in this region6 resulting from damage to the thalamusand hypothalamus7 and midbrain lesions.8

Unilateral as well as bilateral infarction in the territory of theanterior cerebral artery (ACA) is a common cause of mutism withor without akinesia.9;10 AM had been reported following unilateralinfarction involving either the left or right anterior cerebral ar-tery9;11;12 and it is not uncommon to see this syndrome in theperiod soon after dorsal frontal and cingulate lesions. In a study ofthe 10 patients with ACA infarction with involvement of thecingulate gyrus and of them six had AM with four on the right sideand the remaining two in the left, even though five out of the sixand three out of the four had cingulate gyrus involvement.12 It isvery likely the ones that did not show AM at the time of exami-nation could have had AM which had been short-lived. Unilaterallesions are said to give rise to transient akinetic mutism. Inthe case that we have described here (Case 1) AM had continuedfor more than four weeks during the time the patient was underobservation.


Fig. 6 CT scan showing at the levels of the centrum semiovale and corona radiata in the central border zones (right) and in the cortical border zones, dorsolateral

(left) and posterolateral (right) consistent with bilateral watershed infarctions.

Akinetic mutism following stroke 29

According to Meador et al.13 lesions of the cingulate gyrus orSMA or both give rise to akinesia and mutism with restriction ofspontaneous activity. In many ways the anterior cingulate gyrus isvery similar to the SMA and the SMA has afferent and efferentconnections with the cingulate gyrus.14 The side of the lesion,whether right or left is said to produce the same effects. The SMAis concerned with programming, initiating and execution ofmovements and is found to be active during the planning andexecution of complex movements together with the basal ganglia.Lesions of the SMA give rise to decreased activation with hypo-metria and hypokinesia.13 Impaired function of the SMA couldgive rise to abnormalities such as parkinsonian motor perfor-mance15 as many of the structures in the medial frontal and orbito-frontal sub circuits receive dopaminergic innervation. Dopaminereceptor agonists have been shown to cause amelioration ofthe apathy exhibited by some of the patients with akineticmutism.16–18

The frontal lobe plays an important role in the initiation ofbehaviour and speech. Its dysfunction produces lack of spontan-iety and akinesia. Small lesions involving the SMA could give riseto mutism by interrupting the connecting fibres from the SMA tothe frontal lobe motor cortex and with time the speech recovers.There are no language errors and language abnormalities arisefrom larger lesions which involve other projection systems withinthe left hemisphere.19 Transcortical motor aphasia was encoun-tered in one of the four patients with left ACA infarction fol-lowing an initial period of complete mutism12 and in a study by


Borgousslavky et al.20 Mixed transcortical aphasia results fromrecurrent strokes,20 left ACA infarction,21 frontal lobe infarction,22

subcortical lesions such as thalamic and putaminal11;23 and in thesuperior periventricular white matter.24 The case study mentioned4

showed that AM and transcortical aphasia could follow a leftthalamic mesencephalic infarction.

Alexander et al.25 proposed five segregated circuits and eachcircuit linked the frontal lobe, striatum, globus pallidus, substantianigra and the thalamus. Three of them are associated with threedistinct frontal lobe neurobehavioural syndromes.26 The anteriorcingulate syndrome displays akinetic mutism, aspontaniety, in-continence and lack of emotion. Irritability, tactlessness are someof the features associated with orbito-frontal syndrome. Dorso-lateral prefrontal involvement is characterised by reduced verbaland non-verbal fluency and perseveration amongst others.26 Arelationship between basal ganglia and the the frontal corticalareas was proposed by De Long and Georgepolous27 through aconcept of “motor” and “complex” loops. Movement was con-trolled by the motor loop which involve the premotor and sensori-motor cortical areas, the putamen, caudate and a final diencephalicrelay through the nucleus ventralis lateralis to the supplementarymotor area.28 There is a wide network of anatomical structuresinvolved in the eight patients which included frontal lobe andsubcortical structures. Integration of these structures is by way ofthe fronto-subcortical circuits and akinetic mutism could resultfrom damage to the frontal lobe and or interruption of the fronto-subcortical circuitry.


Table 2 Neurological neurobehavioural and neuroimaging findings

Casea Age (years)

Sex

Neurological signs Neurobehavioural

(speech/language)

Neuroimaging Neuroanatomy

1 77 F L sided weakness No speech output (>4 weeks) Infarction R SMA

Markedly akinetic gaze palsy ACAterritory Cingulate gyrus

2 75 M R sided weakness Mute (several days) Infarction L SMA

Initiated movements slow Low volume voice ACA territory Cingulate gyrus

Grasp reflex, forced grasping

tone increased

Aprosodia to anomic aphasia Pre-motor areas

3 38 M R sided weakness Markedly reduced speech

output (>1 week)

Hypodense areas bi Corpus callosum

Alert, eyes open and tracking Slight dysarthria Hemispheric R cinguate

Bilateral extensor plantars Hypophonia L deep parietal

4 72 M Numbness Weakness Mute (3 days) to single words Hypodense area in L caudate Caudate nucleus

R sided slowness of movement

5 79 M R sided weakness Reduced speech output L putaminal haemorrhage L putamen

Prolonged delay to respond Slow swallowing, chewing

(>12 weeks) to perseveration

6 73 M L sided weakness Mute to single words Hypodense areas centrum

semiovale, R corona radiata,

L dorsolateral-frontal,

R posterolateral

Bihemispheric watershed

areas

Reluctance to move limbs Hypophonia

Bilateral signs Aprosodia (~8 weeks)

Grasp reflex +

7 50 M L sided weakness Mute (several days) R thalamic haemorrhage R Thalamus

Gaze palsy Reduced speech output

Generalised slowness Dysarthria

8 64 M L sided weakness Mute L thalamus L Thalamus – mesencephalic

Hypokinetic Reduced speech output to

mixed transcortical aphasia

aAll patients were right handed; SMA, supplementary motor area; ACA, anterior cerebral artery.


REFERENCES

1. Caplan LR, Schmahmann D, Kasi et al. Caudate infarcts. Arch Neurol 1990; 47:133–142.

2. Cairns H, Oldfield HC, Pennybaker JB, Whineridge D. Akinetic mutism withan epidermoid cyst of the third ventricle. Brain 1941; 34: 273–290.

3. Nagaratnam N, Fanello S, Gopinath S, Goodwin A. Prolonged abulia followingputaminal haemorrhage. J Stroke Cerebrovasc Dis 2001; 10: 92–93.

4. Nagaratnam N, McNeil C, Gilhotra JS. Akinetic mutism and mixedtranscortical aphasia following left thalamo-mesencephalic infarction. J NeurolSci 1999; 163: 70–73.

5. Segarra JM. Cerebral vascular disease and behaviour. I. The syndrome of themesencephalic artery. Arch Neurol 1970; 22: 401–418.

6. Hachman HS, Sowers JT, Bruce-Gregoris T. Syndrome of the mesencephalicartery: report of a case with CT and neuropsychological findings. J NeurolNeurosurg Psychiatry 1985; 48: 1179–1181.

7. Shimoda M, Tsugu A, Oda S et al. Development of akinetic mutism andhyperphagia after left thalamic and right hypothalamic lesions. Childs NewSystem 1993; 9: 243–245.

8. Williams D. Cerebral bases of temperament and personality. Lancet 1954; ii:1–4.

9. Bogousslavsky J, Regli F. Anterior cerebral infarctions lausanne stroke registry.Arch Neurol 1990; 47: 144–150.

10. Borggreve F, DeDeyn PP, Marien P et al. Bilateral infarction in the anteriorcerebral artery vascular territory due to an unusual anomaly of the circle ofWillis. Stroke 1994; 25: 2297–2298.

11. Berthier ML, Starkstein SE, Leiguardia R et al. Transcortical aphasia:importance of non-speech dominant hemisphere in language repetition. Brain1990; 1: 631–641.

12. Nagaratnam N, Davies D, Chen E. Clinical effects of anterior cerebral arteryinfarction. J Stroke Cerebrovasc Dis 1998; 7: 391–397.

13. Meador KJ, Watson RT, Bowers D, Heilman KM. Hypometria with hemispatialand limb motor neglect. Brain 1986; 109: 293–305.

14. Damasio AR, Vandstensen GW. Structure and function of the supplementarymotor area. Neurology 1980; 30: 300–359.


15. Benoke R, Rothwell JC, Duk JRP et al. Performance of simultaneous motor actsin normal subjects and in patients with Parkinson’s Disease. Brain 1986; 46:1024–1027.

16. Nagaratnam N, Nagaratnam K. Parkinsonian syndrome following anteriorcerebral artery infarction. Euro J Int Med 1992; 3: 345–350.

17. Ross ED, Stewart JT. Akinetic mutism from hypothalamic damagesuccessful treatment with dopamine agonists. Neurology 1981; 31:11435–11439.

18. Stewart JT, Leadou M, Gonzalez-Rothi LJ. Treatment of a case ofakinetic mutism with bromocriptine. J Neuropsychiat Clin Neurosci 1990; 2:462–463.

19. Kazui S, Sawada T, Naritomi H et al. Angiographic evolution of braininfarction limited to the anterior cerebral artery territory. Stroke 1993; 24:549–553.

20. Bogausslavsky J, Regli F, Assal G. Acute transcortical mixed aphasia. A carotidocclusion syndrome with pial and watershed infarcts. Brain 1988; 11: 631–641.

21. Ross ED. Left medial parietal lobe and receptive with language functions:mixed transcortical aphasia after anterior cerebral infarction. Neurology 1980;30: 144–150.

22. Rapscak SZ, Krupp LB, Rubens AB, Reim MJ. Mixed transcortical aphasiawithout isolation of the speech area. Stroke 1990; 21: 953–956.

23. Nagaratnam N, Gilhotra JS. Acute mixed transcortical aphasia following aninfarction in the left putamen. Aphasiology 1998; 12: 489–493.

24. Nagaratnam N, Barnes R. Language dysfunction in white matter lesions withoutsignificant hemiparesis. J Neurol Rehab 1996; 10: 253–256.

25. Alexander GE, Delaney MR, Strick PL. Parallel organisations of functionallysegregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 1990; 9:357–381.

26. Cummings JL. Frontal-subcortical circuits and human behaviour. Arch Neurol1993; 50: 873–880.

27. DeLong HR, Georgepoulos AP. Motor functions of the basal ganglia asrevealed by studies of single cell activity in the behaving primate. Arch Neurol1979; 24: 131–140.

28. Schell GR, Strick PL. The origin of thalamic infarcts to the arcuate motor andsupplementary motor areas. J Neurol Sci 1984; 4: 539–560.


akinetic mutism following stroke

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