Results

Altogether 25 patients were included in the study; 18 women and seven men. The mean age at disease onset was 65.8 (SD 8.5); range 44–83) years. The mean time between appearance of the first symptoms and occurrence of akinetic mutism was four (range 1.1–11.2) months. The mean duration of disease of all patients was 7.5 (range 2-17) months. The time span between occurrence of akinetic mutism and date of death was a mean of 3.5 (range 0.3–15) months.

CLINICAL PRESENTATION AT THE ONSET AND IN THE COURSE OF THE DISEASE

Seventeen patients (68%) showed signs of a rapidly progressive dementia syndrome at the onset of the disease. Speech disorders with phonematic or semantic paraphasia, dysarthria, perseverations, and impairments in speech understanding were seen in only five cases at the onset. Pseudobulbar speech was noticed in three cases at the beginning of the disease, in two other cases it was noticed during the subsequent observation period. Akinetic mutism never appeared as an initial symptom. In the course of the disease, all patients developed dementia and mutism which often manifested itself in a reduction of spontaneous speech, construction of incomplete sentences, and single word utterances.

CLASSIFICATION ACCORDING TO MASTERS et al6

According to the classification of Masters et al, 22 patients were classified as probable and three as possible cases (later confirmed as definite cases by neuropathological examination). All patients had shown at least two of the four concomitant symptoms previously described which are necessary to assume the potential diagnosis of Creutzfeldt-Jakob disease. In addition, six patients presented disturbances of ocular motor control; two of them had a vertical gaze palsy.

CLASSIFICATION OF THE PATIENTS ACCORDING TO THE DEFINITION AND DESCRIPTION OF THE STATE OF AKINETIC MUTISM BY CAIRNS et al1

Seven of 25 patients fulfilled the criteria of akinetic mutism developed by Cairns et al 1 . These patients were awake, fixed their eyes on the examining person, and reacted to auditory stimuli by moving their eyes (table 1). At the time of the examination one patient was mute but able to walk and perform activities of daily living on his own and was therefore not assigned to a state of an akinetic mutism. In the further progression of the disease he developed an akinetic mutism.

CLASSIFICATION OF THE PATIENTS ACCORDING TO THE SYMPTOMS CONSTITUTING THE COMPLETE PICTURE OF AN APALLIC SYNDROME (GERSTENBRAND)5

Thirteen patients who presented a special kind of impaired consciousness in the sense of a coma vigile were categorised into the complex of symptoms of an apallic syndrome. All these patients showed an impaired sleep-waking cycle and no emotions of any kind. Table 2shows the individual symptoms.The symptoms constituting the complete picture of an apallic syndrome were applied to the seven patients who were in the state of akinetic mutism (table 3). Many of these patients showed a disturbed sleep-waking cycle and a lack of emotions. One patient responded with a smile, another looked reluctantly and was moaning. Oculovestibular reflexes and a coma vigile could not be found. All patients showed a visual fixation of the examining person. The symptoms of these patients thus differ from those present in patients with an apallic syndrome. It is striking that abnormalities of posture and primitive motor patterns occurred twice as often in patients with an apallic snydrome than in patients with akinetic mutism. These symptoms belong to the complex of symptoms 5–8 comprising disinhibited functions after a failure of higher cortical systems. Proportionally, vegetative dysregulation was found more often in patients who were in a state of akinetic mutism. At the time of investigation, four patients had already been comatose—that is, their consciousness was clouded and the sleep-waking cycle was disturbed.7 They are not included in tables 2 and 3.

Discussion

CLINICAL PRESENTATION AT THE ONSET AND IN THE COURSE OF THE DISEASE

After a mean duration of four months, akinetic mutism occurred in 24 patients. However, mutism and akinesis must not develop simultaneously. One patient was in a state of mutism and very apathic; however, he could walk and was able to perform some activities of daily living on his own. In accordance with the definition of Cairns et al 1 this patient, despite his apathy and hypokinesia, cannot be classified as being akinetic and mute. In psychotic disorders also, which originate from a loss of motivation but not from diffuse or circumscribed cerebral lesions, such as catatonia and depression, the term should not be applied. In some of the other 24 patients, who lay motionless in bed, motor activity could also be induced by startling them through auditory stimuli. They often reacted with defensive reflexes of all four limbs and thus proved that, in a state of akinetic mutism, they lie motionless but not paralysed in bed. This aspect is also part of the definition of Cairns et al 1 and Freemon.2

AKINETIC MUTISM ACCORDING TO CAIRNS et al1

Cairns et al 1 describe the symptomatology of their patient with a cyst in the third ventricle with complete immobility, inability to speak, and showing adequate reactions to external stimuli. The condition of a patient with circulatory disturbances in the mesodiencephalic region is characterised similarly by Segarra.8 The patient lay motionless but not paralysed in bed, was somnolent but not comatose, calm but not mute. The akinetic state of the patient of Cairns et al 1 could immediately be remedied by puncture of the cyst. The child could speak normally and did not show any other neurological deficiencies. At the time of the disease, the child’s ability to move and speak seems to have been blocked. There are similar reports from other authors, who noted an improvement in the symptomatology of their patients.9-10 The case study of Lhermitte et al 11 showed that some patients who are in a state of akinetic mutism can even be oriented relative to time and place and show a certain understanding of speech. They could elaborate a communication code with a patient who had developed akinetic mutism after an ischaemic lesion of the reticular formation. By hand movements she indicated as to which of the answers given in choice were correct and, for short periods during the day, she could answer with “yes” and “no”. By contrast with this blockage of speech and motor activity caused by a circumscribed lesion, our patients always developed dementia during a primary degenerative process. According to Kretschmer7 this means a quantitative reduction of cerebral performances, although cerebral functioning is preserved to a certain degree. This process often also affects speech and may entail a veritable degradation of speech. An attempt to develop a communication code with the 25 patients examined, similar to the code elaborated by Lhermitte et al 11 and his patient, was unsuccessful. There is a discrepancy, though, between speech production and speech understanding. One patient, in a prestage to akinetic mutism, was mute but correctly followed simple instructions. This also occurred in some of the patients who were in a state of akinetic mutism. Lebrun defines mutism as a loss of speech while a clearly better speech understanding is preserved.12 This definition is valid for patients with Creutzfeldt-Jakob disease. Several years after its introduction by Cairns et al,1 the term akinetic mutism was more exactly subdivided into a pathologically anatomically localised frontal form and a mesencephalic form and, in accordance with the clinical picture, into a hyperpathic and somnolent form.8 The frontal form occurs in patients with bilateral circulatory disturbances in the supply area of the anterior cerebral artery.2 13-19Other papers state that akinetic mutism occurred in patients with glioblastoma which had infiltrated bilaterally the rostral midline structures and medial parts of the frontal lobe.20 In various papers, examples for mesodiencephalic lesions are given—for example, in the case of a craniopharyngioma in the region of the third ventricle,10 21 damage to the thalamus and hypothalamus,22 a small midbrain lesion,23lesions in the late stage of an obstructive hydrocephalus,24 and circulatory disturbances in the mesodiencephalic region.25 These lesions always go along with perceptive and cognitve deficiencies.3 Our patients would have to be assigned to the mesencephalic type. Segarra8 assigned two different clinical appearance forms to both anatomical localisations: “hyperpathic” akinetic mutism to bilateral frontal lobe damage, “somnolent” or “apathetic” akinetic mutism to the mesencephalic region. On the one hand, both forms can be distinguished by the degree of vigilance and on the other by the preservation of ocular motor control. Mesencephalic damage is typically characterised by vertical gaze palsy and ophthalmoplegia. Interestingly, six patients from the selected group showed disorders of the ocular motor control and two patients a vertical gaze palsy. Our patients would thus have to be assigned to the mesencephalic type and somnolent type of akinetic mutism. By contrast with the case descriptions mentioned above neuropathological findings in the brain of patients with Creutzfeldt-Jakob disease are not limited to the mesencephalon. On light microscopical examination, various degrees of spongiform change was observed in 189 patients examined by Brownet al.26 Lesions were typically seen in the neocortex, thalamus, basal ganglia, and cerebellum, but the comparative severity varied greatly from patient to patient and within different regions of the same brain. Therefore it seems unlikely that a correlation will be found between neuropathological patterns and the akinetic mutism in patients with Creutzfeldt-Jakob disease. Nevertheless, no attempt has not been made, yet.

APALLIC SYNDROME ACCORDING TO GERSTENBRAND5

According to Kretschmer,7 the apallic syndrome may represent the end stage of a chronic or acute process, such as a tumour disease or trauma respectively. Phases of a coma prolongé, parasomnia, and akinetic mutism may preceed a traumatic apallic syndrome which may turn into a coma during the course. The phases of a prolonged coma and parasomnia occur after development of an acute midbrain syndrome and are characterised by persistent coma and a somnolent state in which the eyes of the patient are closed. These phases do not necessarily appear in patients with a degenerative process. However, the 25 patients showed different stages. In the earliest stage of the disease, one patient was mute but not akinetic, seven were in a state of akinetic mutism, 13 in a subsequent stage of an apallic syndrome, and four patients in a final stage of a coma. In the whole course of the disease, there was considerable time variation in reaching the individual stages and the duration of the individual stages. The progression of the symptomatology is reflected in the increase in symptoms appearing from the occurrence of akinetic mutism to the end stage of an apallic syndrome.Comparatively, the symptoms describing a functional loss of higher cortical functions more often occur in patients with an apallic syndrome. This difference is much more obvious in the case of the symptoms characterising a disinhibition of the autonomous functions. They occurred twice as often in patients with an apallic syndrome, except for the feature of a vegetative dysregulation which appeared as an early symptom in both groups. If the description of an apallic syndrome7 with the disturbance of the disinhibitory systems of the brain stem due to a blockage of the pallium is taken as a basis for the division of the symptoms into a complex of symptoms 1–4 and 5–8, the conclusion is reached that decortication in patients with an apallic syndrome shows a more advanced degree of development than patients in a state of akinetic mutism. Akinetic mutism can therefore be considered as a prestage to an apallic syndrome.The coma vigile is an important distinctive feature for the diagnosis of an apallic syndrome and an akinetic mutism. The apallic patients, who are in a coma vigile, seem to be alert with eyes open but do not respond to any external stimulus. Formally, they have to be considered as being comatose. By contrast with these patients, patients in a state of akinetic mutism are alert and able to contact their surroundings, at least by eye contact. This supports the impression of an at least partly preserved activity of consciousness. On the basis of the aforementioned differences between akinetic mutism and an apallic syndrome, the complex symptomatology in patients with Creutzfeldt-Jakob disease should not be simply subsumed under the picture of an apallic syndrome. Patients with Creutzfeldt-Jakob disease have to be assigned to the mesencephalic form of akinetic mutism. They have to be distinguished from akinetic mutism caused by bifrontal brain damage, which creates a distinct syndrome without cognitive deficiencies or other neurological deficiencies. The term akinetic mutism has been used as a classification criterion for the diagnosis of Creutzfeldt-Jakob disease, although the term apallic syndrome would have been more appropriate for many instances. Many patients originally classified as akinetic and mute were probably already apallic. For practical reasons it is not useful to change the classification criteria. Therefore the term akinetic mutism can be applied but should be delimited clearly from the apallic syndrome as a prestage to the same.The main differences on clinical examination are: patients with an apallic syndrome (coma vigile) seem alert but without visual fixation of objects and without evident acitivity of consciousness. By contrast, patients in a state of akinetic mutism are alert with preserved visual fixation of objects. Although the spontanous speech is lost, the activity of consciousness may be evident through better speech understanding and the ability to carry out simple commands.