British Journal of Neurosurgery, June 2004; 18(3): 253 – 258 SHORT REPORT Subarachnoid haemorrhage and akinetic mutism Br J Neurosurg Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 11/19/13 For personal use only. K. A. CHOUDHARI Department of Neurosurgery, Regional Neurosciences Unit, Royal Victoria Hospital, Belfast, UK Abstract Two 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 conditions is 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 of AM associated with aneurysmal subarachnoid haemorrhage (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 the British Medical Association’s OVID Medline + 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 conditions, to discuss its pathophysiology and management. Illustrative cases akinetic mutism. CT of the head showed an interhemispheric 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 postoperative course was complicated by chest infection and vasospasm leading to further neurological deterioration. One month 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. 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 Discussion Akinetic mutism (AM) describes a standard clinical state characterized by akinesia (inability to move) 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: kchoudhari@hotmail.com Received for publication 3 September 2003. Accepted 8 March 2004. ISSN 0268-8697 print/ISSN 1360-046X online/04/030253–06 # The Neurosurgical Foundation DOI: 10.1080/02688690410001732698 Br J Neurosurg Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 11/19/13 For personal use only. 254 K. A. Choudhari FIG. 1. Preoperative plain CT axial scan images showing interhemispheric clot with SAH. FIG. 2. Angiogram showing distal anterior cerebral artery aneurysm (white arrow). 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 summarized in Table I. Non-traumatic AM is most commonly caused by tumours arising from diencephalic 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 atherosclerotic 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 hydrocephalus has also been implicated in a delayed form of AM following SAH.10 Rarely, low intracranial pressure caused by decompressive craniectomy and Br J Neurosurg Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 11/19/13 For personal use only. Subarachnoid haemorrhage and akinetic mutism 255 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 Patricolo, 197134 Buge,19754 Koh, 197915 1 1 1 Von Cramon, 198035 1 Postoperative complication Infarction of ACA region Mass effect caused by the aneurysm Hydrocephalus and bilateral ACA territory infarction Nemeth, 19883 Nishigaya, 199036 Danilewicz, 199010 Lechevalier, 199637 Ushikoshi, 199927 Burruss, 19999 1 1 8 1 1 1 Hodozuka, 200011 Kanemoto, 200014 1 1 Present study 2 Presenting feature of SAH Vasospasm in DACA territories Secondary hydrocephalus Infarction in the left ACA territory Post- GDC coiling complication Unknown, intermittent Low pressure due to craniectomy and T – P shunt Mass effect caused by the aneurysm Intracerebral clot and DACA territory infarction 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 Site of the aneurysm Anatomical level of the lesion AComA AComA Basilar artery Hypothalamus Cingulate gyri Mesencephalic compression AComA Left internal carotid artery bifurcation DACA – AComA Superior cerebellar A – Cingulate gyri + diencephalons Cingulate gyri Cingulate gyri Diencephalic Cingulate gyrus + dienecephalic ischaemia Brain stem – AComA Azygous ACA ?Diencephalic Diencephalic compression AComA and DACA Cingulate gyri 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- 256 K. A. Choudhari 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). Br J Neurosurg Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 11/19/13 For personal use only. 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 functions 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 anatomical 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 deteriorate from one into another. In its classic form, regardless of the cause, the underlying biochemical mechanism of AM is postulated to be selective disruption of mesocoeruleo, diencephalospinal and/or mesocorticolimbic dopaminergic pathways.17 Nemeth and colleagues, in their study of akinetic mutism and locked-in syndrome (LiS) analysed morphological observations 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 systems 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 AM with 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 FIG. 4. Schematic diagram depicting various anatomical regions affected in akinetic mutism. 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-diencephalic Subarachnoid haemorrhage and akinetic mutism 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 SAHinduced AM if spontaneous improvement plateaus. Br J Neurosurg Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 11/19/13 For personal use only. 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 aneurysm. 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 believes 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 endovascular, 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 improvement. 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