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Neuroscience and Biobehavioral Reviews May 2020Akinetic mutism (AM) is a rare neurological disorder characterized by the presence of an intact level of consciousness and sensorimotor capacity, but with a simultaneous... (Review)
Review
Akinetic mutism (AM) is a rare neurological disorder characterized by the presence of an intact level of consciousness and sensorimotor capacity, but with a simultaneous decrease in goal-directed behavior and emotions. Patients are in a wakeful state of profound apathy, seemingly indifferent to pain, thirst, or hunger. It represents the far end within the spectrum of disorders of diminished motivation. In recent years, more has become known about the functional roles of neurocircuits and neurotransmitters associated with human motivational behavior. More specific, there is an increasing body of behavioral evidence that links specific damage of functional frontal-subcortical organization to the occurrence of distinct neurological deficits. In this review, we combine evidence from lesion studies and neurophysiological evidence in animals, imaging studies in humans, and clinical investigations in patients with AM to form an integrative theory of its pathophysiology. Moreover, the specific pharmacological interventions that have been used to treat AM and their rationales are reviewed, providing a comprehensive overview for use in clinical practice.
Topics: Adrenergic Uptake Inhibitors; Akinetic Mutism; Animals; Dopamine Agonists; Dopamine Uptake Inhibitors; Dopaminergic Neurons; GABA-A Receptor Agonists; Gray Matter; Humans; Motivation; Zolpidem
PubMed: 32044373
DOI: 10.1016/j.neubiorev.2020.02.006 -
Therapeutic Advances in Neurological... 2023The locked-in syndrome (LiS) is characterized by quadriplegia with preserved vertical eye and eyelid movements and retained cognitive abilities. Subcategorization,... (Review)
Review
The locked-in syndrome (LiS) is characterized by quadriplegia with preserved vertical eye and eyelid movements and retained cognitive abilities. Subcategorization, aetiologies and the anatomical foundation of LiS are discussed. The damage of different structures in the pons, mesencephalon and thalamus are attributed to symptoms of classical, complete and incomplete LiS and the locked-in plus syndrome, which is characterized by additional impairments of consciousness, making the clinical distinction to other chronic disorders of consciousness at times difficult. Other differential diagnoses are cognitive motor dissociation (CMD) and akinetic mutism. Treatment options are reviewed and an early, interdisciplinary and aggressive approach, including the provision of psychological support and coping strategies is favoured. The establishment of communication is a main goal of rehabilitation. Finally, the quality of life of LiS patients and ethical implications are considered. While patients with LiS report a high quality of life and well-being, medical professionals and caregivers have largely pessimistic perceptions. The negative view on life with LiS must be overthought and the autonomy and dignity of LiS patients prioritized. Knowledge has to be disseminated, diagnostics accelerated and technical support system development promoted. More well-designed research but also more awareness of the needs of LiS patients and their perception as individual persons is needed to enable a life with LiS that is worth living.
PubMed: 37006459
DOI: 10.1177/17562864231160873 -
Cureus Jan 2021Pediatric akinetic mutism syndrome is a clinical disease resulting from cerebellar injury and characterized by the absence of speech or reduced speech, emotional... (Review)
Review
Pediatric akinetic mutism syndrome is a clinical disease resulting from cerebellar injury and characterized by the absence of speech or reduced speech, emotional lability, there may also be hypotonia, oropharyngeal dysfunction/dysphagia, bladder and intestinal incontinence, or other behavioral disorders and neurological signals. It is described as the most recurrent complication in children, after posterior fossa tumor surgery, mainly related to cerebellar midline injuries. An increasing number of research and prospective reviews have provided valuable information on cerebellar mutism syndrome in recent years. The purpose of this review was to elucidate the pathophysiological basis and the predictive factors for this syndrome. Most cases of mutism are due to injury cerebellar tracts and cerebellar-cerebral circuits, involving particularly distinct points of the dentate-thalamus-cortical and dentato-rubro-thalamus-cortical. Advanced neuroimaging techniques, such as tractography and perfusion studies, have contributed to demonstrating changes in these pathways in patients with pediatric cerebellar mutism.
PubMed: 33542880
DOI: 10.7759/cureus.12593 -
Journal of the Academy of... 2021Coronavirus disease 2019 (COVID-19) has been associated with neuropsychiatric complications ranging from new-onset psychosis to delirium, dysexecutive syndromes,... (Review)
Review
BACKGROUND
Coronavirus disease 2019 (COVID-19) has been associated with neuropsychiatric complications ranging from new-onset psychosis to delirium, dysexecutive syndromes, catatonia, and akinetic mutism (AM). AM can be conceptualized as a disorder of motivation wherein patients exhibit a loss of speech and spontaneous movement, owing to disruption of underlying frontal-subcortical circuits.
OBJECTIVES
The objectives of this study were to review the concept and differential diagnosis of AM, as well as the clinical literature on AM in COVID-19 and discuss potential implications for underlying functional neuroanatomy and mechanistic pathways, as well as clinical management.
METHODS
A narrative literature review was performed using PubMed querying published articles for topics associated with AM and its occurrence in COVID-19.
RESULTS
AM has been described in case reports and a prospective cohort study of patients with COVID with neurological complaints. Three COVID-19 AM subgroups can be distinguished, including individuals with severe respiratory illness, those with meningoencephalitis, and those with delirium and pre-existing neuropsychiatric illness. Electrophysiology and functional imaging suggest COVID-19 AM may result from underlying frontal lobe dysfunction and disruption of associated distributed circuits subserving goal-directed behavior. Distinctive combinations of pathophysiological mechanisms may be at play in the different subgroups of COVID-19 AM cases.
CONCLUSION
AM has been described in association with COVID-19 and may manifest in clinically heterogenous subgroups with distinct underlying mechanisms. The diagnosis of AM and evaluation of potential etiologies can be complex. The occurrence of AM contributes evidence to the hypothesis of frontal lobe dysfunction in COVID-19.
Topics: Akinetic Mutism; COVID-19; Humans; Motivation; Prospective Studies; SARS-CoV-2
PubMed: 34461295
DOI: 10.1016/j.jaclp.2021.08.009 -
BJPsych Bulletin Aug 2023Catatonia has been increasingly described in cases of COVID-19; we therefore aimed to investigate the evidence for catatonia in patients with COVID-19. We searched... (Review)
Review
AIMS AND METHOD
Catatonia has been increasingly described in cases of COVID-19; we therefore aimed to investigate the evidence for catatonia in patients with COVID-19. We searched PubMed, EMBASE, PsycINFO, BIN and CINAHL databases for articles published in English, from the initial descriptions of the COVID-19 pandemic to January 2022.
RESULTS
A total 204 studies were identified, 27 (13%) of which met the inclusion criteria. The evidence available was based on case reports. The articles included in this review identified a total of 42 patients, ranging from the ages of 12 to ≥70 years, with confirmed or possible catatonia during or after a COVID-19 infection.
CLINICAL IMPLICATIONS
This review provides valuable information to clinicians in medical practice for treating patients with COVID-19, and a foundation for further research for this uncommon syndrome of COVID-19.
PubMed: 35670192
DOI: 10.1192/bjb.2022.30 -
Annals of Clinical and Translational... Apr 2021Many neurological manifestations are associated with COVID-19, including a distinct form of encephalopathy related to cytokine storm, the acute systemic inflammatory... (Review)
Review
OBJECTIVE
Many neurological manifestations are associated with COVID-19, including a distinct form of encephalopathy related to cytokine storm, the acute systemic inflammatory syndrome present in a subgroup of COVID-19 patients. Cytokine storm is also associated with immune effector cell-associated neurotoxicity syndrome (ICANS), a complication of chimeric antigen receptor T-cell (CAR-T) therapy, a highly effective treatment for refractory hematological malignancies. We investigated whether COVID-19-related encephalopathy, ICANS, and other encephalopathies associated with cytokine storm, share clinical and investigative findings.
METHODS
Narrative literature review.
RESULTS
Comparisons between COVID-19-related encephalopathy and ICANS revealed several overlapping features. Clinically, these included dysexecutive syndrome, language disturbances, akinetic mutism and delirium. EEG showed a prevalence of frontal abnormalities. Brain MRI was often unrevealing. CSF elevated cytokine levels have been reported. A direct correlation between cytokine storm intensity and severity of neurological manifestations has been shown for both conditions. Clinical recovery occurred spontaneously or following immunotherapies in most of the patients. Similar clinical and investigative features were also reported in other encephalopathies associated with cytokine storm, such as hemophagocytic lymphohistiocytosis, sepsis, and febrile infection-associated encephalopathies.
INTERPRETATION
COVID-19-related encephalopathy and ICANS are characterized by a predominant electro-clinical frontal lobe dysfunction and share several features with other encephalopathies associated with cytokine storm, which may represent the common denominator of a clinical spectrum of neurological disorders. Therefore, we propose a unifying definition of cytokine storm-associated encephalopathy (CySE), and its diagnostic criteria.
Topics: Brain; Brain Diseases; COVID-19; Cytokine Release Syndrome; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen
PubMed: 33780166
DOI: 10.1002/acn3.51348 -
Frontiers in Human Neuroscience 2022This paper presents a case in whom a differential diagnosis of akinetic mutism with a disorder of consciousness was made using diffusion tensor tractography (DTT). A...
This paper presents a case in whom a differential diagnosis of akinetic mutism with a disorder of consciousness was made using diffusion tensor tractography (DTT). A 69-year-old female patient was diagnosed with subarachnoid hemorrhage, intraventricular hemorrhage, and intracerebral hemorrhage produced by the subarachnoid hemorrhage. She exhibited impaired consciousness with a Coma Recovery Scale-Revised score of 13 until 1 month after onset. Her impaired consciousness recovered slowly to a normal state according to the Coma Recovery Scale-Revised (23 points: full score) at 7 weeks after onset. On the other hand, she exhibited the typical clinical features of akinetic mutism (no spontaneous movement [akinesia] or speech [mutism]). On the DTT performed at 1-month, the upper, and lower dorsal ascending reticular activating systems, which are related to a disorder of consciousness, showed an almost normal state. In contrast, the prefronto-caudate and prefronto-thalamic tracts, which are related to akinetic mutism, showed severe injuries. These DTT results suggested that the patient's main clinical features were not a disorder of consciousness but akinetic mutism. Therefore, DTT for the ascending reticular activating system, and the prefronto-caudate and prefronto-thalamic tracts could provide additional evidence for a differential diagnosis of DOC and AM at the early stages of stroke.
PubMed: 35280207
DOI: 10.3389/fnhum.2022.778347 -
Brain, Behavior, & Immunity - Health Aug 2021
Review
PubMed: 34002170
DOI: 10.1016/j.bbih.2021.100272