Akinetic mutism, resulting from anterior communicating artery aneurysm rupture, with subarachnoid hemorrhage and anterior cerebral artery distribution infarcts
A CT scan of the head was performed, which showed subarachnoid hemorrhage as well as bifrontal (anterior cerebral artery distribution) infarcts. The patient was taken emergently for dye angiography, which showed a saccular anterior communicating artery aneurysm and vasospasm in the A1 and M1 segments. The aneurysm was surgically clipped, and the patient was treated with "triple H" therapy (hypervolemia, hypertension, and hemodilution) as well as with nimodipine. However, a follow up angiogram the next day showed continued vasospasm, and angioplasty of the A1 and M1 segments was performed, with the intent of improving blood flow to affected regions. The patient tolerated this procedure, but later suffered another infarct, involving the parietal lobe.
The patient convalesced and underwent extensive physical and occupational therapy, but remained akinetic and mute at the time of discharge, four months after her presentation. She remained in a rehabilitation facility for several months, and was discharged to home. Subsequent outpatient follow up has documented little significant improvement.
Neurological disorders of volitional movement or speech output are frequently difficult to distinguish from primarily psychiatric presentations of illness. In this patient's case, circumstantial evidence (her obvious depression, suicide attempts, and recent multi-substance drug abuse) initially suggested the latter. However, persistence of her disability, as well as development of fever and urinary incontinence, occasioned a thorough search for an underlying disease process. In any unresponsive, febrile patient receiving neuroleptic medications, the neuroleptic malignant syndrome should be considered. However, no significant alteration of muscle tone was documented to support this possibility. Examination of the patient documented global hypokinesia and apathy, as well as subtle lateralizing signs. Neuroimaging demonstrated subarachnoid hemorrhage and vasospasm associated with an anterior communicating artery aneurysm. We note that the patient did not endorse the symptom of headache, and no meningeal signs were detected on examination, despite the presence of considerable subarachnoid hemorrhage on the CT study.
Apathy, which is derived from the Greek word pathos, can be defined as the absence of feeling, interest or concern. Abulia, derived from the Greek word boul (will), is usually defined as lack of will or an inability to decide.[1] C. Miller Fisher, in an presentation at a national Neurosurgery meeting, suggested that akinetic mutism represented abulia in its most extreme form.[2] The differential diagnosis of the volitional disorders of movement or speech is vast. They may be seen as part of a recognized personality disorder, such as avoidant or schizoid personality disorders. They may develop as a response to socio-environmental factors such as imprisonment, retirement, or a natural disaster. Apathy is frequently seen in affective and psychotic disorders such as major depression and schizophrenia.[1] Major medical illnesses may also be associated with apathy or abulia during the course of illness, presumably relating either to systemic influences on brain function or psychiatric responses to the impact of illness.
There have been numerous case reports of akinetic mutism in the literature. The first mention of the term was in a paper published in 1941 by Cairns et al., discussing the findings of a 14 year old girl with craniopharyngioma.[3] Since then there have been documented cases associated with lesions (both stroke and tumor) in the cingulate gyri, midbrain and thalamus, as well as processes in the third ventricle. Cases of akinetic mutism have also been described in association with hydrocephalus, encephalitis lethargica and traumatic encephalopathy.[2]
The anatomic sites reported to be affected in cases of akinetic mutism generally represent structures comprising the mesencephalofrontal activating system (MAS). The MAS involves dopaminergic neuron cell bodies in the substantia nigra and the ventral tegmentum of the midbrain, which project to the frontal and cingulate gyri (as well as to the locus coeruleus and to the dorsal gray matter of the spinal cord).[4] These observations have led many to treat akinetic mutism with dopaminergic medications. When the lesion causing akinetic mutism is in the frontal lobe, occasional favorable responses to L-DOPA or dopamine agonists such as bromocriptine have been reported.[5] Akinetic mutism associated with mesencephalic lesions has been suggested to respond to dopamine agonists.[6] However, in most cases, especially those associated with systemic insults such as anoxia, there is minimal response even to dopamine agonists.[7]
Akinetic mutism is unusual and is quite striking in its presentation, even in the typical case. At an affiliated hospital, the Methodist Hospital, Burruss and Chacko reported the case of a patient without volitional activity following rupture of a basilar artery aneurysm. He remained in this state for years until he had a brief resumption of his pre-morbid persona following a generalized tonic-clonic seizure. Intermittent amelioration of his disability associated with similar circumstances occurred four more times in the next year, which prompted a therapeutic trial of electroconvulsive therapy (ECT). The ECT treatments did lead to brief "awakenings" following the first two treatments. However, further ECT did not ameliorate the akinetic-mute state and the treatments were halted.[8] C. Miller Fisher described a patient who lay in an akinetic-mute state after an anterior cerebral artery infarct for months, only to converse fluently for a minute or two when Dr. Fisher telephoned him directly. Dr. Fisher reported this "telephone effect" to be present in over three-fourths of the patients he had seen with akinetic mutism, and suggested the possible existence of alternative pathways to initiate communication as an explanation.[3]
Cerebral vasospasm may be present in up to 70% of all patients with subarachnoid hemorrhage.[9] Occurrence of vasospasm peaks 4-10 days after initial bleeding, causing focal cerebral ischemia and ultimately infarction. In a recent study, patients with ultra-early angiographic vasospasm (within 48 hours of presumed onset of hemorrhage) were reported to be at high risk for clinically significant vasospasm and poor outcome. Early surgery appeared to neither ameliorate nor aggravate this risk.[10]
Treatment of cerebral vasospasm frequently involves "triple-H" (hypervolemia, hypertension, and hemodilution) therapy. This approach employs colloid or crystalloid volume expansion, often combined with a vasopressor such as dopamine or phenyephrine. Nimodipine, originally recognized as a blocker of L-type calcium channels, has been accepted treatment of cerebral vasospasm for over a decade. Numerous reports suggest treatment of fever to ameliorate ischemic brain damage in a variety of cerebral insults, and induced hypothermia is under study as a possible intervention in patients with subarachnoid hemorrhage-induced vasospasm. Trials are also underway for erythropoietin, which has exhibited neuroprotective effects in addition to its effects on red cell mass, and newer vasodilators such as fasudil, a Rho kinase inhibitor.[9]
Our patient was also treated with angioplasty of intracranial vessels exhibiting persistent spasm. Although some literature supports this intervention,[11,12] a recent multi-center trial did not suggest significant clinical benefit from angioplasty after symptomatic vasospasm despite excellent angiographic results.[13] At this point, the timing and indications for endovascular approaches to symptomatic cerebral vasospasm remain to be defined.
We thank Dr. R. Glenn Smith, formerly of the Neurology Service at the Ben Taub General Hospital, for his valuable input and suggestions in this case. Dr. Smith currently is at the Department of Neurology, University of Texas Medical Branch (Galveston).
-- Dennis R. Mosier, M.D., Ph.D.
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