Three patients developed akinetic mutism on the third day after the introduction of intravenous cyclosporin A, given for immunosuppression after liver transplantation. One patient in addition developed a florid orofacial dyskinesia, which resolved completely, as did the akinetic mutism, after withdrawal of cyclosporin. In these patients the time course of the akinetic mutism and extrapyramidal syndrome, which developed in the absence of any other identifiable cause, suggests cyclosporin A was the precipitating factor. Subsequently, two of the patients showed signs of pseudobulbar palsy with abnormalities in the pons on MRI scanning, suggesting central pontine myelinolysis (CPM). None of the patients had experienced significant fluctuations in serum sodium or other risk factors for central pontine myelinolysis and the exact relationship to the earlier cyclosporin related mutism was not clear.
An account is given of six cases of Jakob-Creutzfeldt disease confirmed at necropsy. The rapid fatal outcome within three months was typical of the variety designated subacute spongiform encephalopathy (Nevin-Jones). The characteristic EEG changes were found to be of great value in making an early diagnosis and, together with akinetic mutism and myoclonus, constituted an easily recognizable picture. Treatment with idoxyuridine was ineffective in one case in which electronmicroscopy of brain biopsy material supported the diagnosis.
The syndrome of the mesencephalic artery refers to the clinical constellation of akinetic mutism and third nerve palsy which results from occlusion of one or more of the posterior thalamo-perforating arteries that arise from the proximal posterior cerebral artery. A patient with this syndrome is described in whom a bilateral paramedian midbrain infarct was shown by computed tomography and confirmed pathologically. To our knowledge, this is only the second reported case of mesencephalic infarct shown by computed tomography and the first in which the CT findings have been corroborated by pathological examination.
Three cases of bilateral anterior cerebral artery occlusion are presented with akinetic mutism. The anatomical distribution of the infarction in these patients combined with cases in the literature suggests that this syndrome can have a localizing value for the clinician. If increased intraventricular pressure is not present, the clinician can suspect a bilateral lesion of cingulate gyrus, medial nuclei of basal ganglia, and/or anterior and reticular nuclei of the thalamus.
Since a report in 1996 of 10 cases of Creutzfeldt-Jakob disease
(CJD) with onset in a younger than usual age, a pattern of the disease
has emerged. This includes early neuropsychiatric features and sensory
symptoms and neurological signs such as ataxia and involuntary
movements later in the course of the disease. Three patients with
varied clinical presentations and disease course seen at a single
neurology unit are described. The first patient was characterised by
cognitive and psychiatric symptoms together with neurological signs.
The second patient presented with unusual behavioural disturbance and
episodes of collapse. The third patient exhibited striking psychomotor
retardation and had abnormal CSF and MRI findings. All patients
succumbed in a state of akinetic mutism and myoclonus. All three
patients had the methionine/methionine genotype at codon 129 of the PrP
gene and in two of the three patients a tonsil biopsy was performed with positive results. These two patients also tested positive for the
14.3.3. protein in the CSF. Whereas late features of the disease seem very similar in all cases,
the initial presentation was variable and underlines the uncertainty of
the range of the clinical phenotype. Successful diagnosis demands a
high index of clinical suspicion.
OBJECTIVES—Among the classification criteria for
the diagnosis of Creutzfeldt-Jakob disease, akinetic mutism is
described as a symptom which helps to establish the diagnosis as
possible or probable. Akinetic mutism has been anatomically divided
into two forms—the mesencephalic form and the frontal form. The aim of
this study was to delimit the symptom of akinetic mutism in patients
with Creutzfeldt-Jakob disease from the complex of symptoms of an
apallic syndrome and to assign it to the individual forms. METHODS—Between April and December 1996, 25 akinetic and mute patients with Creutzfeldt-Jakob disease
were consecutively examined. The patients were classified according to
the definition of akinetic mutism by Cairns and secondly in accordance
with the features constituting the complete picture of an appalic
syndrome (defined by Gerstenbrand). RESULTS—From 25 patients with definite
Creutzfeldt-Jakob disease, 24 patients showed impoverishment of
speech and, after a mean duration of four (range 1.1-11.2) months,
almost complete absence of voluntary movements and speech. Seven
patients were classified as being mute and akinetic and assigned to the
mesencephalic form whereas 13 patients were classified as apallic. One
patient was mute without being akinetic and four patients were comatose. CONCLUSION—Diffuse brain damage underlies akinetic
mutism in patients with Creutzfeldt-Jakob disease. The term can be used
as a classification criterion for the diagnosis of Creutzfeldt-Jakob
A case is reported of idiopathic CD4+T lymphocytopenia with
progressive multifocal leukoencephalopathy and cervical lymph node
tuberculosis. A 57 year old Japanese man presented with cervical lymphadenopathy and progressive neurological deficits, and six months
later he developed akinetic mutism. He had a persistent severely
depressed number of circulating CD4+T lymphocytes in the absence of
human immunodeficiency virus infection. T1 weighted MRI showed a
diffuse decreased signal intensity limited to the white matter without
mass effect. A brain biopsy specimen had a morphology similar to that
of progressive multifocal leukoencephalopathy. Polyomavirus antigen was detected in the brain lesion, and viral DNA
was identified in nucleated blood cells and urine. Unusually this
serious medical condition has lasted for more than three years without
remission. To our knowledge this is the first patient with
CD4+T lymphocytopenia with progressive multifocal
leukoencephalopathy, suggesting that similar opportunistic infections
should be considered even in previously normal people.
An opportunity to study the effects of methylmercury poisoning in humans was provided by the large outbreak in Iraq in 1971-2. In adults, poisoning resulted from the ingestion of home-made bread prepared from methylmercury-treated seed grain and there was a highly significant correlation between the amount of bread ingested and blood mercury levels. Poisoning in infants resulted either from prior exposure in utero or from suckling or both. Blood mercury levels were higher in infants and children than in adults. There was no increased incidence of congenital defects. Symptoms and signs of poisoning and histopathological changes were mainly confined to the CNS. Symptoms developed, on average, 1-2 months after exposure. In children there was mental retardation with delayed onset of speech and impaired motor, sensory and autonomic function. Severely affected children were blind and deaf. In adults, the clinical picture could be classified as 1, mild (mainly of sensory symptoms) 2, moderate (sensory symptoms accompanied by cerebellar signs) and 3, severe (gross ataxia with marked visual and hearing loss which, in some cases, progressed to akinetic mutism followed by coma). Grades 1 and 2 carried a better prognosis thant grade 3. Interference with transmission at the myoneural junction was found in 14% of patients studied. There was no evidence of peripheral nerve involvement per se and sensory symptoms may be of central origin. The clinical differences between the Iraqi and Japanese outbreaks may be a result...
A 42-year-old man with left posterior inferior cerebellar artery (PICA) infarction presented with akinetic mutism and cognitive impairment. Initially he suffered from akinetic mutism and MRI-documented infarction in the distribution of the left PICA. Twelve days later he developed cognitive impairment. Neuropsychological tests were performed, with the results corrected for age and education being compared with published Korean norms. Impaired performances were evident on executive function testing, with difficulties in planning, abstract reasoning, set-shifting, and perseveration. Akinetic mutism and cognitive-affective syndrome may be a manifestation of unilateral PICA infarction.
In 1968, the Harvard criteria equated irreversible coma and apnea (i.e., brain death) with human death and later, the Uniform Determination of Death Act was enacted permitting organ procurement from heart-beating donors. Since then, clinical studies have defined a spectrum of states of impaired consciousness in human beings: coma, akinetic mutism (locked-in syndrome), minimally conscious state, vegetative state and brain death. In this article, we argue against the validity of the Harvard criteria for equating brain death with human death. (1) Brain death does not disrupt somatic integrative unity and coordinated biological functioning of a living organism. (2) Neurological criteria of human death fail to determine the precise moment of an organism’s death when death is established by circulatory criterion in other states of impaired consciousness for organ procurement with non-heart-beating donation protocols. The criterion of circulatory arrest 75 s to 5 min is too short for irreversible cessation of whole brain functions and respiration controlled by the brain stem. (3) Brain-based criteria for determining death with a beating heart exclude relevant anthropologic, psychosocial, cultural, and religious aspects of death and dying in society. (4) Clinical guidelines for determining brain death are not consistently validated by the presence of irreversible brain stem ischemic injury or necrosis on autopsy; therefore...
A case of central anticholinergic syndrome due to overdosage of trihexyphenidyl hydrochloride presenting as septal akinetic mutism with unequally dilated pupils is discussed in reference to similar presentation in animals and possible clinical application.
The purpose of this study is to determine the characteristic clinical features, radiologic findings, and precipitating and prognostic factors in the patients with breast cancer and with 5-Fluorouracil (5-FU)-induced leukoencephalopathy. We reviewed the medical records of six breast cancer patients who developed leukoencephalopathy after chemotherapy which included 5-FU and also evaluated thorough neurological examinations including mini-mental status examination, cerebrospinal fluid studies, brain images and brain biopsies. Six patients exhibited slowly progressing neurologic symptoms characterized by the impairment of cognitive function, abulia, ataxic gait, and/or akinetic mutism. None of the patients had any specific causes or etiologic factors for leukoencephalopathy. Brain MRI in all patients showed diffuse periventricular white matter changes in the T2-weighted MR image. Brain biopsy in Patient 1 showed fragmented axonal fiber and minimally deprived myelination with many scattered macrophages. Five patients who treated with steroids at the onset of neurological symptoms showed clinical improvement, regardless of their age, sex, the pathology and stage of breast cancer, or the total dosage of chemotherapeutic agents. We conclude that leukoencephalopathy in these cases could be attributable to 5-FU neurotoxicity and suggest that the administration of steroids might be the treatment of choice.
Normal human consciousness requires brainstem, basal forebrain, and diencephalic areas to support generalized arousal, as well as functioning thalamocortical networks to become aware of, and respond to environmental and internal stimuli. Injury to or disconnection of these interconnected systems, typically from cardiac arrest and traumatic brain injury, can result in disorders of consciousness, including coma, vegetative state, minimally conscious state, and akinetic mutism. Similar brain injuries can also result in loss of motor output out of proportion to consciousness, resulting in misdiagnoses of disorders of consciousness. We review pathology and imaging studies and derive mechanistic models for each of these conditions, to aid in the assessment and prognosis of individual patients. We further suggest how such models may guide the development of target-based treatment algorithms to enhance recovery of consciousness in many of these patient.
Mutations in the glucocerebrosidase gene (GBA1) cause Gaucher disease (GD) and are the most common genetic risk factor for the development of Parkinson’s disease (PD). Here, we present a 12-year follow-up study of a male with GD and PD (diagnosed 24years ago), which PD preceded the clinical manifestation of GD by 12years. The patient is a compound heterozygote for mutations c.115+1G>A and c.1226A>G (IVS2 + 1/N370S) in the GBA1 gene. Imiglucerase had a beneficial effect on GD, but not on PD. Treatment with L-dopa and other PD drugs showed temporary efficacy but 2years later significant wearing-off phenomenon and dyskinesias appeared. Unilateral pallidotomy was performed with transient benefit. Cognitive decline appeared later and developed in to akinetic mutism. A lumbar puncture was performed to characterize the biochemical profile of cerebrospinal fluid (CSF). Analyses of monoamine metabolites levels in the CSF, determined by reverse-phase high-performance liquid chromatography, revealed remarkably low levels of all studied monoamine metabolites (HVA, DOPAC, 5-HIAA, MHPG). These data indicate that PD associated with GBA1 mutations may not only affect dopaminergic neurons, but also noradrenergic and serotonergic neurons. Of note...
Akinetic mutism is described in various clinical presentations but typically is defined as a state wherein the patient appears awake but does not move or speak. It can be divided into two different subtypes; the most common subtypes depend on the lesion location, mesencephalic-diencephalic region, also called apathetic akinetic mutism (somnolent mutism), and those involving the anterior cingulate gyrus and adjacent frontal lobes called hyperpathic akinetic mutism. The pathway of akinetic mutism is believed to originate from circuits that link the frontal and subcortical structures. This case reports a 48-year-old African American female with bilateral anterior cerebral artery stroke and akinetic mutism with coexisting thyroid storm. This patient with bilateral anterior cerebral artery infarcts presented with characteristics that are typical for akinetic mutism such as having intact eye movements but an inability to respond to auditory or visual commands. With the incidence of bilateral anterior cerebral artery (ACA) ischemic stroke being rare and the incidence of akinetic mutism secondary to ischemic stroke even rarer, we suspect that this patient potentially had a unilateral occlusion of anomalous anterior cerebral vasculature.
El mutismo acin??tico es considerado como una alteraci??n del estado motivacional de la persona, por la cual el paciente es incapaz de iniciar respuestas verbales o motoras de car??cter voluntario, a??n teniendo reservadas las funciones sensoriomotoras y de vigilancia. La lesi??n, que puede ser vascular, infecciosa, t??xica o degenerativa, incide sobre dos circuitos que podr??an estar funcionalmente relacionados: el cortex frontal medial con afectaci??n del c??ngulo anterior, o el da??o en regiones tal??micas y mesencef??licas relacionadas con la formaci??n reticular activadora ascendente.
El diagn??stico de mutismo acin??tico resulta a veces dif??cil de establecer, y suele confundirse con algunos tipos de afasias o estados de alteraci??n de la conciencia, que tienen un abordaje cl??nico y un pron??stico notablemente diferentes. Con el objetivo de llevar a cabo un buen diagn??stico diferencial proponemos un protocolo cl??nico con una evaluaci??n neuropsicol??gica breve de las funciones que pudieran estar diferencialmente afectadas en todos esos s??ndromes, como atenci??n, praxias y lenguaje. Exponemos un caso de mutismo evaluado con este protocolo para demostrar su especificidad a la hora de distinguirlo de otras afecciones o s??ndromes.; Akinetic mutism is considered as a disturbance of a person??s motivational state...
Abulia refers to an impairment of will, or the inability to initiate behaviour and action. There are reports of successful treatment of akinetic mutism, the most severe form of abulia, with bromocriptine. Four case studies are presented describing the successful treatment of abulia at a lesser severity than akinetic mutism with bromocriptine. Abulia was caused by brain damage due to alcohol in two cases, Wilson's disease and basal ganglia infarct in one each. Maximum bromocriptine dose varied from 25-70 mg. All improved considerably. Withdrawal or reduction of medication in three produced deterioration. The prescription of a neuroleptic drug had a similar effect in the fourth. One patient with a previous history developed a depressive relapse and so the drug was withdrawn and lisuride introduced. This produced a similar improvement. These cases highlight the value of identifying the syndrome of organic abulia and suggest that dopamine agonists may have a place in its treatment, though controlled studies are needed.
Progressive multifocal leucoencephalopathy (PML) may pose a clinical and diagnostic dilemma. The patient may remain in a protracted psychotic state with negative symptoms, without overt features of dementia. The condition blends with catatonia, and eventually with akinetic mutism in a patient of AIDS in the absence of clinical evidence of an immunocompromised state. The present case report highlights the need for an in-depth clinical, biochemical and MRI assessment of patients with catatonia and akinetic mutism. Stupor of an ‘akinetic mutism’ pattern seems an important indication for HIV screening, particularly in high-risk patients.