akinetic mutism: a report of three cases

Acia Neurol Scand 1998: 98: 439444 Prinied in UK - all righis reserved

Copyright 0 Munkrgaard 1998 ACTA NEUROLOGICA

SCANDINAVlCA ISSN 0001-6314

Akinetic mutism: a report of three cases

Ure J, Faccio E, Videla H, Caccun R, Giudice F, Ollan J, Diez M. Akinetic mutism: a report of three cases. Acta Neurol Scand 1998: 98: 439-444. 0 Munksgaard 1998.

Objectives - To report 3 new cases of akinetic mutism, a clinical syndrome defined by silent immobility with preserved visual alertness not accountable by lesion of the areas and/or effector pathways of speech and voluntary movements. Material and methods - Anatomopathological studies were

I performed in Cases 1 and 2; clinical follow-up, EEG, angiography and CT scans in Case 3. Results - Case 1: Bipallidal necrosis; Case 2: Left pallidal necrosis with right frontoparietal cortico-subcortical infarction; Case 3: Striato-capsular infarction on the left side, involving the caudate nucleus and the anterior arm of the internal capsule, together with obstructive hydrocephalus. Conclusion -The roles of both globus pallidus and prefronto- striatal circuits in the onset of voluntary movements are discussed.

Akinetic mutism (AM) (1) is a clinical syndrome liable to be induced by diversely localized lesions almost invariably bilateral, either frontal, subcortical white matter, pallidal, thalamic or midbrain, that arise from very heterogeneous causes (vascular, toxic, infectious, tumoral, degenerative or traumatic). It is characterized by a silent immobility with preservation of motor pathways and speech centres, with the sole behavioural manifestation of ocular mobility.

Here we describe our personal observations on 3 new cases of AM, 2 with post-mortem brain examination, briefly discussing the pathophysiology of this syndrome.

Case reports

Case 1

This 55-year-old male with a history of chronic alcoholism was admitted due to akinesia, mutism, arterial hypertension and fever. When the last two disorders had been corrected, his status remained unchanged. Neurological examination showed ocular mobility, mutism and lack of response to simple commands, the patient closely following the examiner's movements with his gaze. Lower limbs were flexed and hypertonic with neither osteoten- dinous hyperreflexia nor Babinski sign. He died a month later due to a lung infection, with the same

* Deceased February 28th, 1993.

J. Ure', E. Faccio", H.Videla', R. Caccuri', F. Giudice', J. Ollari', M. Diez' Departments of 'Neurology. and 'Pathology, Borda Hospital, Buenos Aires. Argentina

Key words akinetic rnutism. bipallidal lesions. striato- capsular infarction

Dr Jorge Ure. Rebizo 455 (1842) Monte Grande, Buenos Aires. Argentina

Accepted for publication July 28. 1998

rigidity in lower limbs of the extrapyramidal type, and the above-mentioned AM status.

The brain, weighing 1200 g, was fixed in 10% formaldehyde for 25 days. On observation, there was a bilateral lacunar condition of the putamen, with softened areas in both globus pallidus (lateral and medial sectors) and severe arteriosclerosis in cerebral vessels, with atheromatosis of the basilar artery and of both internal carotid arteries in their supraclinoidal portions. No significant alterations in white matter were disclosed by myelin techniques. The right pallidal focus (Fig. 1) involved the medial sector and the lateral one in its anterior portion, while in the posterior portion only the lateral area was affected, corresponding to the medial part of the anterior white commissure. The left pallidal area (Fig. 2) presented similar alterations, somewhat more widespread, involving the most ventral fibres of the internal capsule.

Case 2

This 55-year-old male had a history of chronic alcoholism and Korsakoff syndrome. Admitted due to dysarthria, urinary incontinence and right brachial monoparesis, 15 days later he acutely developed a left hemiparesis. Neurological examination disclosed ocular mobility, absent or mono- syllabic speech, scarce response to pain, preserved response to visual and auditory stimuli and a partially flexed posture in upper limbs. Subsequent

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Fig. 1. Case 1. Coronal section at anterior white commisure level (Weigert-Pal) showing vascular focus within right globus pallidus (arrow).

to this picture compatible with Ah4 and left facio- brachio-crural hemiparesis, he died a month later due to infectious complications.

At autopsy the brain, weighing 1150 g, was fixed in 10% formaldehyde for 25 days. Widespread softened areas were observed cortico-subcortically in the right cerebral hemisphere, involving the frontal lobe at the level of the corpus callosum genu, 30 mm

Fig. 2. Case 1. Coronal section at anterior white commisure level (Weigert-Pal) showing vascular focus within right globus pallidus (arrow), localized within its anterior dorsal area.

Fig. 3. Case 2. Coronal section (Weigert-Pal) at left anterior thalamic nucleus level showing a cavitated left pallidal area involving almost the whole medial sector and some fibres adjacent to the genu of the internal capsule.

outwardly, the parietal lobe and the right angular gyms in the most external and posterior portion of the infarct, together with a 30x20 mm softened cystic area in the anterior region of the left globus pallidus (Fig. 3) and moderate arteriosclerosis of the mixed to predominantly fibrous type in cerebral vessels. Gross observation was corroborated by myelin techniques, which also showed that the softened area on the right interrupted fibres from the ventral and medial layers crossing the corpus callosum genu, as well as a cavitated left pallidal area involving almost the whole medial sector and some fibres adjacent to the genu of the internal capsule. In most posterior sections the infarct became more superficial. Lastly, there was partial degeneration of pyramidal pons fibres on the right side that spared the cortico-geniculo-pontine fascicle and at geniculate level the pyramid was in some sections paler on the right side.

Case 3

This 36-year-old female presented with headache, vomiting, dysarthria and fainting. On admission, haemorrhagic cerebrospinal fluid (CFS) was col- lected. An angiogram and a CT scan were performed, disclosing a saccular aneurysm at the proximal segment of the left anterior cerebral artery, and a hypodensity in the CT scan involving

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Fig. 4. Case 3. Coronal CT scan showing hypodense image in left anterior capsular region (arrow) without mass effect compatible with anterior cerebral artery subcortical infarct probably due to vasospasm after an aneurysmatic bleeding.

the head of the caudate nucleus and the anterior arm of the left internal capsule (Fig. 4). The EEG showed frontal delta waves bilaterally placed. Neurological examination showed visual and pal- pebral response to menace, neck stiffness without meningeal response, decortication rigidity on the right side and conjugate ocular deviation to the left. Later the patient developed hydrocephalus (Fig. 5 ) , with right abducens paresis, bilateral papillary oedema, bilateral Babinski sign and mydriasis on the right side with normal photomotor response. She was operated on 15 days after admission, on the day following CT confirmation of hydrocephalus, with placement of a ventriculo-peritoneal shunt. Twenty-four h later she developed AM, though with minimal left hand movements and masticatory automatisms, with neither facial nor vocal response to pain. She died 20 days later due to an oesophago- bronchial fistula with subsequent lung infection. No autopsy was performed.

Discussion

Cases 1 and 2 featured considerable anatomical destruction of the globus pallidus. In Case 1 the lesion was bilateral; in Case 2 it was restricted to the left side, but AM manifested subsequently to extensive contralateral cortico-subcortical soften- ing that interrupted interhemispheric connective fibres. Howes & Boller (2) reported that right

Fig. 5. Case 3. Second CT, 11 days after Fig. 4. It shows ventricular dilatation with periependymal oedema due to progressive hydrocephalus.

hemisphere infarctions are associated with a greater slowing of reaction times (hypokinesia) than left hemispheric lesions. Verfaellie et al. (3) used a reaction time paradigm capable of fully dissociating attention from intention, also showing that the right hemisphere was dominant for intention. Cases 1 and 2 were alcoholics, a condition associated with relative mediofrontal hypometabolism of unclear origin (4).

Cravioto et al. ( 5 ) reported a case of AM, contending that the syndrome arose from bipallidal necrosis due to lighting gas poisoning. According to Denny-Brown (6), a state of AM often follows poisoning by carbon monoxide, lighting or kitchen gas, carbon dioxide, nitrous oxide, carbon disul- phide or, more rarely, other types of anoxic asphyxia, featuring rigidity in all four limbs, or flexion of upper and extension in lower limbs. The remaining 7 cases described by Cravioto et al. (3, with extensive pontine lesions due to thrombotic occlusion of the basilar artery, represented a locked-in syndrome because of damage to descend- ing motor pathways.

The appearance of AM subsequent to left pallidal lesion has been reported by Brage et al. (7) and by Vitale (8). In the former case, the lesion extended to the genu of the internal capsule and to the anterior white commissure, while in the latter, the ventrolateral thalamic nucleus was also injured by a stereotactic intervention.

Other authors (9, 10) extend the concept of AM to certain settings of extreme abulia, subsequent to anterior striato-capsular infarcts, or limited to the genu of the internal capsule (ll), interpreted as thalamo-cortical disconnection between the intralaminar nuclei and the frontal cortex by involve- ment of the anterior arm of the internal capsule or

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Fig. 6. Schematic diagram of motor cortex activation highlighting circuits selectively impaired to cause AM. ACC receives fibres of hypothalamic origin connecting the system with internal needs. CMPFN activate ventral thalamus while RN can inhibit VA and VL thalamic nuclei. CMPFN and RN are connected with MRF and may receive environmental stimuli. S and GP play a key role in co- ordinating both subsystems (SMA-ACC and CMPFN-RN) with the prefrontal, premotor and motor cortices. SMA: supplementary motor area, ACC: anterior cingulate cortex, RN: reticular thalamic nucleus, CMPFN: centromedian parafascicular nuclei, S: striatum, G P globus pallidus, VA and VL ventral anterior and ventral lateral thalamic nuclei and MRF: midbrain reticular formation.

of the lower portion of its genu. Akiguchi et al. (12) proposed the term “anterior thalamic peduncle syndrome” for this clinical condition.

De Smet et al. (13) presented a case of bilateral striatal infarct followed by tetraparetic mutism involving the upper portion of the internal capsule within the territory of the medial cerebral artery. Previously, Hawke & Donohue (14) had stated that symmetrical bilateral destruction of the striatum produces a picture of cognitive deterioration with the absence of voluntary movements. Richter & Kliiver (15) reported the case of a monkey that suddenly developed akinesia upon suffering bilateral caudate and putamen degeneration due to acute encephalopathy. Although it opened its eyes, it failed to withdraw its limbs from a heat source, thus resembling a clinical AM setting.

The globus pallidus forms a functional complex with the neostriatum, the latter being the afferent sector. The complex receives fibres from the

supplementary motor area (SMA), the anterior cingulate cortex (ACC) and the intralaminar nuclei, projecting to the anterior and lateral ventral thalamic nuclei which activate the prefrontal, premotor and motor cortices. According to Kornhuber (16) and Delong & Strick (17), the basal ganglia generate uniform and slow movements, voluntary in nature. By means of functional and structural magnetic resonance imaging (MRI), Bucher et al. (18) observed that lateral pallidal lesions proved inhibitory for the thalamus inducing slowness in movements (hypokinesia), whereas medial lesions had the opposite effect (hyperkine- sia). In post-mortem pallidal studies in parkinso- nian patients, Foster et al. (19) found increased striatal inhibition on the lateral globus pallidus, presumably due to nigral lesion.

The SMA would appear to act upon planning a movement mentally (20,21), while the ACC would link hypothalamic stimuli with prefrontal areas,

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affecting motivational aspects of spontaneous verbal and gestural behaviour (22) or suppression standards of cortical activity (23). The bicingulate lesion, for instance, subsequent to aneurysmatic rupture in the anterior cerebral artery, as in our Case 3, or in the anterior communicating artery, provides another possible cause of AM (22,2428). Nemeth et al. (27) suggest that the ACC and the SMA should be simultaneously damaged to induce this type of AM, and point out that dopaminergic deficiency in mesolimbocortical projections plays a role in its pathogenesis. Ljunberg & Ungerstedt (29) reported that the interruption of dopaminergic axons projecting from the lateral hypothalamus through the medial forebrain bundle (MFB) induces a behavioural picture similar to AM, which can be reversed by administering apomorphine (30).

According to Ross & Stewart (31), the treatment of AM with bromocriptine, a dopaminergic agonist, may prove useful if the lesion is restricted to the mesencephalic tegment or to the hypothalamus (posterior AM), but it is ineffective if the lesion involves the ACC (anterior AM), because dopaminergic receptors would have been damaged. The motivational nature of cortical AM (SMA and ACC lesion) was documented by Damasio & Van Hoesen (32), who described a patient developing an embolic infarct in the SMA and ACC on the left side who remained speechless during a month, to say later that “she did not speak because she had nothing to say”.

The existence of the other variant of anterior AM, that of subcortical origin, has been questioned by Tatemichi et al. (33), while Weiller et al. (34) believed it could be interpreted as a subcortical aphasia. For their part, De Smet & Brucher (13) regarded it as an anterior AM, with less impact than posterior AM on ocular mobility, when the patient tends to be more stuporous. In our Case 3, the patient suffered a striato-capsular left infarct, but the hydrocephalic decompensation could also have contributed to cause AM (35). Although the causative lesion of AM may be in the centromedian parafascicular (CMPF) nuclei (36-44), due to bilateral butterfly-wing infarcts secondary to obstruction of the posterior thalamic-subthalamic artery (of the retromammillar pedicle) that dis- connects activating thalamic nuclei, patent hypo- perfusion was found in the prefrontal area at SPECT (49, as well as bilateral frontal hypoperfu- sion in bilateral thalamo-capsular lesions (46), suggesting impairment of the fronto-striato-pallido-thalamo-frontal circuit advanced by Laplane et al. (47).

On inserting the intralaminar (CMPF) (and reticular thalamic) (48) nuclei into such circuit

(Fig. 6), all the possible lesion locations liable to induce AM are included. This circuit is operative in triggering motor activation, and its dysfunction leads to AM, with the sole sparing of voluntary ocular movements, whose cortical representation would exceed the limits of such circuit.

In conclusion, the presentation of 3 new cases of AM plus the review of the literature points to the presence of neural networks co-ordinated for motor activation, that is, to prepare the motor cortex for action. Such structures include: 1) the SMA and ACC that channel the decision to move, the latter receiving DA stimulation from the hypothalamus; 2) the thalamic nuclei that make up the various parts of the system: thus, impulses originating from external sources through the reticular formation with the cortico-striatal impulses; the CMPF nuclei acting as motor activators while the reticular nucleus would act as inhibitor; and 3) the lateral globus pallidus makes a contribution to initiate the movement while the striatum (putamen and caudate nucleus) and the medial pallidus may modulate such initiative. Finally, the ventrothalamo-prefronto-premotor and motor circuits that complete the loop become operative.

Acknowledgement

Paula Doumanian is acknowledged for providing artwork.

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akinetic mutism: a report of three cases

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