Treatment of chronic akinetic mutism with atomoxetine: subtraction analysis of brain f-18 fluorodeoxyglucose positron emission tomographic images before and after medication: a case report.

Akinetic mutism is a rare, complex neuropathologic disorder. The pharmaceutical treatment of akinetic mutism typically includes dopaminergic agents, but the resulting therapeutic effects are often unsatisfactory, and it remains unclear whether late treatment using these medications is effective. We present a case study of a 53-year-old male patient who developed akinetic mutism for a period of 7 months after a subarachnoid hemorrhage. The hemorrhage was caused by a ruptured aneurysm in the right anterior communicating artery, followed by a secondary infarction in the territory of the right anterior cerebral artery. Baseline brain F-18 fluorodeoxyglucose positron emission tomographic images revealed decreased glucose metabolism in both frontal lobes. Treatment with atomoxetine, a selective norepinephrine reuptake inhibitor, for a period of 8 weeks led to a clinically significant improvement in the patient's cognitive function and activities of daily living. A subtraction brain positron emission tomographic analysis after atomoxetine medication revealed increased cerebral glucose metabolism in both the premotor and visual association cortices. Thus, we suggest that atomoxetine can be a useful therapeutic option in the treatment of chronic akinetic mutism.

Frontal lobe and cingulate cortical metabolic dysfunction in acquired akinetic mutism: a PET study of the interval form of carbon monoxide poisoning.

A middle-aged man suffering from acute carbon monoxide intoxication was clinically assessed to be in an akinetic and mute state. In order to elucidate regional cerebral disturbances, brain metabolism was investigated with fluoro-deoxyglucose positron emission tomography ((18)FDG-PET) 5.5 months after intoxication. Significantly reduced metabolic rates of glucose were revealed in selected brain regions, especially in both the frontal and anterior cingulate cortices, as well as in the subcortical white matter. Frontal and cingulate cortices showed a preserved metabolism of 35-53%, whereas the regional glucose consumption in cerebral white matter was reduced by more than 70%. In contrast, other areas of the brain such as the sensory-motor cortex, parts of the temporal lobes, basal ganglia and brainstem disclosed normal metabolic values. This lesion topography is discussed in relation to the development of akinetic mutism in the present case and in comparison with recent reports on the topic. Considering a plausible pathophysiology, akinetic mutism appears to be based on a different structural neuropathology when compared with the locked-in syndrome and the vegetative state. It is suggested that akinetic mutism is regarded as a specific condition characterized by injury of the frontal neuronal systems which promote executive functions.

Residual cerebral activity and behavioural fragments can remain in the persistently vegetative brain.

This report identifies evidence of partially functional cerebral regions in catastrophically injured brains. To study five patients in a persistent vegetative state (PVS) with different behavioural features, we employed [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET), MRI and magnetoencephalographic (MEG) responses to sensory stimulation. Each patient's brain expressed a unique metabolic pattern. In three of the five patients, co-registered PET/MRI correlate islands of relatively preserved brain metabolism with isolated fragments of behaviour. Two patients had suffered anoxic injuries and demonstrated marked decreases in overall cerebral metabolism to 30-40% of normal. Two other patients with non-anoxic, multifocal brain injuries demonstrated several isolated brain regions with relatively higher metabolic rates, that ranged up to 50-80% of normal. Nevertheless, their global metabolic rates remained <50% of normal. MEG recordings from three PVS patients provide clear evidence for the absence, abnormality or reduction of evoked responses. Despite major abnormalities, however, these data also provide evidence for localized residual activity at the cortical level. Each patient partially preserved restricted sensory representations, as evidenced by slow evoked magnetic fields and gamma band activity. In two patients, these activations correlate with isolated behavioural patterns and metabolic activity. Remaining active regions identified in the three PVS patients with behavioural fragments appear to consist of segregated corticothalamic networks that retain connectivity and partial functional integrity. A single patient who suffered severe injury to the tegmental mesencephalon and paramedian thalamus showed widely preserved cortical metabolism, and a global average metabolic rate of 65% of normal. The relatively high preservation of cortical metabolism in this patient defines the first functional correlate of clinical- pathological reports associating permanent unconsciousness with structural damage to these regions. The specific patterns of preserved metabolic activity identified in these patients do not appear to represent random survivals of a few neuronal islands; rather they reflect novel evidence of the modular nature of individual functional networks that underlie conscious brain function. The variations in cerebral metabolism in chronic PVS patients indicate that some cerebral regions can retain partial function in catastrophically injured brains.

Akinetic mutism: pharmacologic probe of the dopaminergic mesencephalofrontal activating system.

Four children who exhibited akinetic mutism during the course of their neurologic diseases were treated with bromocriptine. Reversal of the akinetic mute states was evident in all patients. Pathways of the dopaminergic neurons are reviewed and a clinically useful mechanism which causes akinetic mutism is postulated.

Akinetic mutism in a bone marrow transplant recipient following total-body irradiation and amphotericin B chemoprophylaxis. A positron emission tomographic and neuropathologic study.

We describe a case of akinetic mutism associated with diffuse cerebral leukoencephalopathy, which developed in a bone marrow transplant recipient following total-body irradiation and amphotericin B chemoprophylaxis. A trial of high-dose bromocriptine did not stimulate purposeful verbal or motor activity. Fluorine 18-fluorodeoxyglucose/positron emission tomographic studies, performed before and during bromocriptine therapy, demonstrated cerebral hypometabolism and treatment-related decreases in regional cerebral blood volume. We conclude that whole-brain or total-body irradiation may increase blood-brain barrier permeability to polyene antibiotics, and that high-dose therapy with dopamine agonists is unlikely to benefit patients with akinetic mutism due to diffuse white-matter lesions.

[Cerebral hemodynamics in the vegetative state patients--relationship between patterns of dysautoregulation and prognosis (author's transl)].

The pathophysiological analysis of cerebral hemodynamic mechanisms and its metabolism in the vegetative patients was not enough until now. It was reported in this paper that the correlation between cerebral hemodynamics, metabolism and neurological function was analysed in 14 patients with vegetative state caused by cerebrovascular disorders. The materials consist of 14 vegetative patients due to 7 hypertensive intracerebral hemorrhage, 6 subarachnoid hemorrhage and one cerebral infarction. In all of them, the cerebral hemodynamics such as cerebral blood flow (CBF), CO2 reactivity and autoregulation, and cerebral metabolism were measured sequencially by 133Xe clearance methods. In the majority of cases, both values of mean hemispheric CBF and cerebral oxygen consumption (CMRO2) were markedly decreased with severe impairments of autoregulation and CO2 reactivity on the bilateral hemispheres but much more significatly on the affected hemispheres. Futhermore, from view points of the pressureflow relationship in the CBF studies, the patterns of dysautoregulation could be classified into 2 types as follows; Type 1 is the complete loss type, which has no plateau formation in all ranging of systemic arterial blood pressure (SABP). Type 2 is the incomplete loss type with 2 subdivisions, in which the abnormal narrowing plateaus are recognized in relatively higher or lower range of SABP (called as the upper or the lower type of incomplete loss type respectively). And then, the phenomen, which we gave a term as "shift-off phenomenon", was recognized in 8 cases that the proper values of resting SABP was seated outside the plateau level of the auto-regulatory capacity. The correlation between CBF dynamics and the grade of vegetative state was analysed. In 2 cases with slight communications (vegetative grade1), mean hemispheric CBF value was 32.5 (ml/100 g/min.) and CMRO2 was 2.01 (ml/100 g/min.) with the normal or the upper type in incomplete loss of dysautoregulation. In 3 cases of vegetative grade 2, who could slightly response to vocal order, mean CBF and CMRO2 showed 27.0 +/- 2.0 and 1.7 +/- 0.08 respectively. In these cases, dysautoregulations with the upper type incomplete loss were recognized. In 3 cases of vegetative grade 3, who had only spontaneous movement of body and slight emotional expression but no response to vocal order, mean CBF was in 22.4 +/- 1.9 and CMRO2 in 1.28 +/- 0.21. The patterns of dysautoregulation showed the lower type of incomplete loss. We had experienced the shift-off phenomenon in all of 5 cases with the upper type of incomplete loss and in 3 of 7 cases with the lower type of incomplete loss dysautoregulation. As conclusion, in cases of vegetative grade 2 or 3 whose patterns of dysautoregulation are the upper or lower type of incomplete loss with the shift-off pnenomenon, it would be a useful therapeutic method to get away from vegetative state that SABP could be corrected and controlled within the proper plateau level of autoregulation by the suitable administration of some vasoactive agents.