Medical management for cerebellar mutism syndrome following posterior fossa surgery: A systematic review.

INTRODUCTION: Cerebellar mutism syndrome (CMS) is a serious complication of posterior fossa surgeries affecting mainly pediatric age group. The pathophysiology is still not fully understood. It adversely affects the recovery of patients. There is no definitive and standardized management for CMS. However pharmacological therapy has been used in reported cases with variable effectiveness. We aim through this review to summarize the available evidence on pharmacological agents used to treat CMS. METHOD: A thorough systematic review until December 2022, was conducted using PubMed Central, Embase, and Web of Science, databases to identify case reports and case series of CMS patients who underwent posterior fossa surgery and received pharmacological treatment. Patients with pathologies other than posterior fossa lesions were excluded from the study. RESULTS: Of 592 initial studies, 8 studies met our eligibility criteria for inclusion, with 3 more studies were added through manual search; reporting on 13 patients. The median age of 13 years (Standard deviation SD=10.60). The most frequent agent used was Bromocriptine. Other agents were fluoxetine, midazolam, zolpidem, and arpiprazole. Most patients recovered within 48 hours of initiating medical therapy. The median follow-up period was 4 months (SD=13.8). All patients showed complete recovery at the end of follow-up period. CONCLUSION: Cerebellar mutism syndrome is reported after posterior fossa surgeries, despite attempts to identify risk factors, pathophysiology, and management of CMS, it remains a challenging condition with significant morbidity. Different Pharmacological treatments have been proposed with promising results. Further studies and formalized clinical trials are needed to evaluate available options and their effectiveness.

Akinetic mutism following bilateral parasagittal meningioma occupied supplementary motor area removal and the spontaneous recovery of symptoms.

Background: Resection of bilateral parasagittal meningiomas of the dominant cortex is challenging. Some postoperative consequences are difficult to predict due to their low incidence. However, it is essential to recognize reversible symptoms. Akinetic mutism is a devastating but reversible symptom that occurs after supplementary motor area (SMA) injury. This report aims to provide more information to support the clinical progression of this syndrome. Case Description: A 47-year-old woman presented with psychomotor retardation and subtle weakness, particularly on the left side. A palpable mass was identified at the head vertex. Magnetic resonance imaging revealed bilateral parasagittal meningiomas with bone and sinus invasion of the SMA. A craniotomy was performed to remove the intracapsular tumor. Two days after the operation, the patient developed gradual deterioration in her motor function until it became a lock-in-like syndrome. Then, 1.5 months after treatment in the hospital and rehabilitation unit, she gradually improved her motor, cognitive, and psychomotor skills. Total recovery was achieved after 1 year. Conclusion: Surgery for lesions involving bilateral SMA can cause akinetic mutism. The typical manifestation of this syndrome may be devastating. However, it is reversible, and patients can regain full motor and cognitive functions over time without specific treatments. It is crucial to persevere and continue to provide the best care to the patient until recovery.

Akinetic mutism and gait disturbance in a patient with delayed post-hypoxic leukoencephalopathy.

We report on a patient with delayed post-hypoxic leukoencephalopathy (DPHL) who showed akinetic mutism and gait disturbance, neural injuries that were demonstrated on diffusion tensor tractography (DTT). A patient was exposed to carbon monoxide (CO) and rapidly recovered; however, two weeks after onset, he began to show cognitive impairment and gait disturbance. At six weeks after CO exposure, he showed akinetic mutism and gait inability. DTT at 6-weeks post-exposure showed discontinuations in neural connectivities of the caudate nucleus to the medial prefrontal and orbitofrontal cortex in both hemispheres. In addition, the corticoreticulospinal tract revealed severe thinning in both hemispheres.

Molecular and immunological origins of catatonia.

Catatonia occurs secondary to both primary psychiatric and neuromedical etiologies. Emerging evidence suggests possible linkages between causes of catatonia and neuroinflammation. These include obvious infectious and inflammatory etiologies, common neuromedical illnesses such as delirium, and psychiatric entities such as depression and autism-spectrum disorders. Symptoms of sickness behavior, thought to be a downstream effect of the cytokine response, are common in many of these etiologies and overlap significantly with symptoms of catatonia. Furthermore, there are syndromes that overlap with catatonia that some would consider variants, including neuroleptic malignant syndrome (NMS) and akinetic mutism, which may also have neuroinflammatory underpinnings. Low serum iron, a common finding in NMS and malignant catatonia, may be caused by the acute phase response. Cellular hits involving either pathogen-associated molecular patterns (PAMP) danger signals or the damage-associated molecular patterns (DAMP) danger signals of severe psychosocial stress may set the stage for a common pathway immunoactivation state that could lower the threshold for a catatonic state in susceptible individuals. Immunoactivation leading to dysfunction in the anterior cingulate cortex (ACC)/mid-cingulate cortex (MCC)/medial prefrontal cortex (mPFC)/paralimbic cortico-striato-thalamo-cortical (CSTC) circuit, involved in motivation and movement, may be particularly important in generating the motor and behavioral symptoms of catatonia.

Unconsciousness or unresponsiveness in akinetic mutism? Insights from a multimodal longitudinal exploration.

The clinical assessment of patients with disorders of consciousness (DoC) relies on the observation of behavioural responses to standardised sensory stimulation. However, several medical comorbidities may directly impair the production of reproducible and appropriate responses, thus reducing the sensitivity of behaviour-based diagnoses. One such comorbidity is akinetic mutism (AM), a rare neurological syndrome characterised by the inability to initiate volitional motor responses, sometimes associated with clinical presentations that overlap with those of DoC. In this paper, we describe the case of a patient with large bilateral mesial frontal lesions, showing prolonged behavioural unresponsiveness and severe disorganisation of electroencephalographic (EEG) background, compatible with a vegetative state/unresponsive wakefulness syndrome (VS/UWS). By applying an unprecedented multimodal battery of advanced imaging and electrophysiology-based techniques (AIE) encompassing spontaneous EEG, evoked potentials, event-related potentials, transcranial magnetic stimulation combined with EEG and structural and functional MRI, we provide the following: (i) a demonstration of the preservation of consciousness despite unresponsiveness in the context of AM, (ii) a plausible neurophysiological explanation for behavioural unresponsiveness and its subsequent recovery during rehabilitation stay and (iii) novel insights into the relationships between DoC, AM and parkinsonism. The present case offers proof-of-principle evidence supporting the clinical utility of a multimodal hierarchical workflow that combines AIEs to detect covert signs of consciousness in unresponsive patients.

Case report: Levodopa-responsive parkinsonism with akinetic mutism after ventriculo-peritoneal shunt.

Background: Parkinsonism and akinetic mutism (AM) following ventriculo-peritoneal shunt (VPS) without underdrainage used to be considered rare, but may be underdiagnosed in daily clinical practice. Although the pathophysiology is still unclear, in several case reports, the parkinsonism and AM after VPS shows responsiveness to dopaminergic treatment. Case presentation: We report a 19-year-old male that presented with severe parkinsonism and AM after VPS. Meanwhile, 18F-FDG-PET showed a cortical and subcortical hypometabolism. Fortunately, levodopa dramatically improved patient's symptoms and brain hypometabolism. This report provides support for the possibility that dopamine deficiency inhibits brain metabolism, and further elucidates the pathogenesis of parkinsonism and AM. Conclusion: This report highlights the presentation of a treatable parkinsonism and points out that Levodopa and/or dopamine agonist should be the first choice if the patients develop parkinson-like symptoms after VPS.

Management dilemma in a rare case of pituitary apoplexy with akinetic mutism in the setting of ruptured junctional brain aneurysm: A case report and literature review.

Backgound: Pituitary apoplexy is associated with stroke, head injury, and brain tumors. Still, its presentation due to the ruptured aneurysm is rare and its presentation with akinetic mutism has not been reported. Case Description: The patient in the present study is 21-year-old female who presented in our emergency department in an altered sensorium with Glasgow comma score (GCS) E2V1M1. She was intubated and resuscitated. Routine blood investigations, lipid profile, and hormonal studies were normal. Initial noncontrast computed tomography (NCCT) head revealed subarachnoid hemorrhage in the interhemispheric fissure and evidence of bleeding in the pituitary gland. Magnetic resonance imaging (MRI) brain was soon done, which showed an infarct and hemorrhage in the pituitary gland; there was an evidence of an infarct in the bilateral medial frontal gyrus, basal ganglia, and supplementary motor area. MR arteriography revealed an aneurysm at the left A1-anterior communicating artery (Acom) junction directed superomedially with diffuse spasm in a bilateral anterior cerebral artery. Pterional craniotomy was done with clipping of the aneurysm and evacuation of blood clots from the interhemispheric fissure and pituitary gland. Histopathology features suggestive of the non-functioning pituitary tumor with interspersed hemorrhagic necrosis. Intraarterial vasodilation with microcatheter injection was given, but vasospasm did not improve. Postoperatively, Levodopa was started. She used to track objects in front of her eye and started nodding her head in "yes and no fashion," with power in limbs improved to 3/5 at 6 months of follow-up. Conclusion: Pituitary apoplexy with ruptured A1-Acom junction aneurysm with nonfunctioning pituitary macroadenoma is rare, and its presentation with akinetic mutism has not been reported. As there is scarce literature suggesting an association between pituitary apoplexy and ruptured aneurysm, it is challenging to comment regarding its pathogenesis. Although akinetic mutism generally has a poor prognosis, it may respond to Levodopa with a better outcome.

Catatonia after COVID-19 infection: scoping 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.

Demographic Features, Physical Examination Findings, and Medication Use in Hospitalized, Delirious Patients With and Without COVID-19 Infection: A Retrospective Study.

BACKGROUND: Delirium is common in the setting of infection with severe acute respiratory syndrome coronavirus 2. Anecdotal evidence and case reports suggest that patients with delirium in the setting of Coronavirus 2019 (COVID-19) may exhibit specific features, including increased tone, abulia, and alogia. OBJECTIVE: To determine whether differences exist in sociodemographic and medical characteristics, physical examination findings, and medication use in delirious patients with and without COVID-19 infection referred for psychiatric consultation. METHODS: We undertook an exploratory, retrospective chart review of 486 patients seen by the psychiatry consultation service at a tertiary care hospital from March 10 to May 15, 2020. Delirious patients were diagnosed via clinical examination by a psychiatric consultant, and these patients were stratified by COVID-19 infection status. The strata were described and compared using bivariate analyses across sociodemographic, historical, objective, and treatment-related variables. RESULTS: A total of 109 patients were diagnosed with delirium during the study period. Thirty-six were COVID-19+. Median age was 63 years and did not differ between groups. COVID-19+ patients with delirium were more likely to present from nursing facilities (39% vs 11%; Fisher's exact test; P = 0.001) and have a history of schizophrenia (11% vs 0%; Fisher's exact test; P = 0.011). Myoclonus (28% vs 4%; P = 0.002), hypertonia (36% vs 10%; P = 0.003), withdrawal (36% vs 15%; P = 0.011), akinesia (19% vs 6%; P = 0.034), abulia (19% vs 3%; P = 0.004), and alogia (25% vs 8%; P = 0.012) were more common in COVID-19+ patients. COVID-19+ delirious patients were significantly more likely to have received ketamine (28% vs 7%; P = 0.006), alpha-adrenergic agents besides dexmedetomidine (36% vs 14%; P = 0.014), and enteral antipsychotics (92% vs 66%; P = 0.007) at some point. CONCLUSIONS: Patients with COVID-19 delirium referred for psychiatric consultation are more likely to reside in nursing facilities and have a history of schizophrenia than delirious patients without COVID-19. Patients with delirium in the setting of COVID-19 may exhibit features consistent with akinetic mutism. Psychiatrists must assess for such features, as they may influence management choices and the risk of side effects with agents commonly used in the setting of delirium.

Case Report: Acute Necrotizing Encephalopathy Following COVID-19 Vaccine.

Objectives: Acute necrotizing encephalopathy (ANE) is a rare neurological disorder arising from a para- or post-infectious "cytokine storm. "It has recently been reported in association with coronavirus disease 2019 (COVID-19) infection. Methods: A 56-year-old male with a diagnosis of ANE 48 h following the first dose of ChAdOx1 nCoV-19 vaccination was investigated. Cytokine analyses on serum and cerebrospinal fluid (CSF) were performed. The patient was treated with high-dose corticosteroids and followed clinically and radiologically. Results: Favorable clinical and radiological outcomes were noted. There was an upregulation in serum levels of CXCL5, CXCL1, Il-8, IL-15, CCL2, TGF-B, and EGF, and up-regulation in CSF levels of CXCL5, IL-2, IL-3, and IL-8. Discussion: As COVID-19 infection has been previously reported as a possible rare cause of ANE, we speculate on an aberrant immune response mechanism that was brought about by the vaccine. To increase our understanding of the pathogenesis of ANE in the context of COVID-19 vaccination and to better define its clinical features and outcomes, clinicians and scientists should continue reporting convincing cases of such entities.

Differential Diagnosis of Akinetic Mutism and Disorder of Consciousness Using Diffusion Tensor Tractography: A Case Report.

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.

Akinetic Mutism and Coronavirus Disease 2019: A Narrative 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.

The Understanding of Pediatric Akinetic Mutism.

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.

System degeneration in an MM1-type sporadic Creutzfeldt-Jakob disease case with an unusually prolonged akinetic mutism state.

Methionine/methionine type 1 (MM1-type) sporadic Creutzfeldt-Jakob disease (sCJD), known as the 'classic type,' shows typical clinicopathological sCJD findings. In general, patients reach an akinetic mutism state within a few months of disease onset and die soon after if supportive therapies are not administered. Here, we describe remarkable neuropathologic observations of MM1-type sCJD in a 48-year-old, Japanese man with an unusually prolonged akinetic mutism state. In the early disease stages, the patient exhibited abnormal behaviour with gait disturbance and rapidly progressive cognitive dysfunction. Diffusion-weighted magnetic resonance imaging revealed extensive cerebral cortical hyperintensity. Prion protein (PrP) gene analysis revealed no mutations, and the polymorphic codon 129 exhibited methionine homozygosity. Although the patient remained stable with tube feeding for more than 2 years after reaching the akinetic mutism state, he died because of central respiratory failure 30 months after disease onset. Neuropathologic investigation showed extensive devastating lesions, such as status spongiosus, and typical spongiform changes could no longer be observed in the cerebral neocortex. Conspicuous pyramidal tract degeneration was observed. However, the regions commonly preserved in MM1-type sCJD pathology were still relatively preserved. Immunostaining revealed extensive diffuse synaptic-type PrP deposition in the grey matter. The pathological findings suggested that sCJD is a neurodegenerative disease that shows system degeneration; there are primary and secondary degenerative regions and distinct preserved regions, even in cases with prolonged disease duration. In addition, it is considered that there is a limited survival period for MM1-type sCJD, even if active symptomatic treatment is provided.

Case Report: Catatonic Stupor in Behavioral Variant Frontotemporal Dementia.

Catatonia is a psychomotor syndrome common to several medical and neuropsychiatric disorders. Here, we report on the case of a 95-year-old woman who underwent a radical change in personality characterized by sexual disinhibition, and physical and verbal aggressiveness. Over several months, she developed verbal stereotypies, gait deterioration, and double incontinence. She eventually developed mutism and an active opposition to all attempts to be fed or cared for. Benzodiazepines, olanzapine and electroconvulsive therapy were of no benefit. Magnetic resonance imaging revealed asymmetric (more severe on the right) frontotemporal, parietal, and upper brainstem atrophy. She died from sepsis without recovering from stupor seven years after the onset of symptoms. We believe that the initial behavioral disinhibition was related to the frontotemporal injury, whereas catatonic stupor reflected the progression of the degenerative process to the parietal cortices. Our case adds to the small number of cases of catatonia as a symptom of degenerative dementia. It also supports the idea that damage to the parietal cortex gives rise to pathological avoidance of which catatonic stupor represents an extreme form.

Delirium in COVID-19: A case series and exploration of potential mechanisms for central nervous system involvement.

INTRODUCTION: Neuropsychiatric manifestations of the coronavirus disease 2019 (COVID-19) have been described, including anosmia, ageusia, headache, paresthesia, encephalitis and encephalopathy. Little is known about the mechanisms by which the virus causes central nervous system (CNS) symptoms, and therefore little guidance is available regarding potential workup or management options. CASES: We present a series of four consecutive cases, seen by our psychiatry consultation service over a one-week period, each of which manifested delirium as a result of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). DISCUSSION: The four cases highlighted here all occurred in older patients with premorbid evidence of cognitive decline. Unique features seen in multiple cases included rigidity, alogia, abulia, and elevated inflammatory markers. In all four cases, a change in mental status was the presenting symptom, and three of the four cases lacked significant respiratory symptoms. In addition to discussing unique features of the cases, we discuss possible pathophysiologic explanations for COVID-19 delirium. CONCLUSIONS: Delirium should be recognized as a potential feature of infection with SARS-CoV-2 and may be the only presenting symptom. Based on the high rates of delirium demonstrated in prior studies, hospitals should consider adding mental status changes to the list of testing criteria. Further research is needed to determine if delirium in COVID-19 represents a primary encephalopathy heralding invasion of the CNS by the virus, or a secondary encephalopathy related to systemic inflammatory response or other factors.

On the pathophysiology and treatment of akinetic mutism.

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.

Akinetic mutism and status epilepticus due to Epstein Barr virus encephalitis.

Neurological complications of Epstein Barr virus (EBV) infection are infrequent and may include occasionally encephalitis, usually with a benign evolution. We here report on an aggressive case of EBV encephalitis in a 14-year-old boy with extensive basal ganglia involvement, and to a lesser degree of brain cortex who presented atypically with akinetic mutism and non-convulsive status epilepticus, requiring intensive care but showed a favorable outcome. EBV encephalitis is uncommon and its best management is unclear. Its pathophysiology is not well understood but could include autoimmunity. Onconeuronal and synaptic antibodies were negative in serum and cerebrospinal fluid, including the dopamine D2 receptor. To the best of our knowledge, this is the first report to evaluate antibodies to D2 receptors in EBV encephalitis. Corticosteroid therapy is usually recommended but the use of acyclovir is controversial. Intensive care is required in severe cases to assure a favorable outcome.