Steroid-Responsive Encephalitis in Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) infection has the potential for targeting the central nervous system, and several neurological symptoms have been described in patients with severe respiratory distress. Here, we described the case of a 60-year-old patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but only mild respiratory abnormalities who developed an akinetic mutism attributable to encephalitis. Magnetic resonance imaging was negative, whereas electroencephalography showed generalized theta slowing. Cerebrospinal fluid analyses during the acute stage were negative for SARS-CoV-2, positive for pleocytosis and hyperproteinorrachia, and showed increased interleukin-8 and tumor necrosis factor-α concentrations. Other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of cerebrospinal fluid parameters was observed after high-dose steroid treatment, thus arguing for an inflammatory-mediated brain involvement related to COVID-19. ANN NEUROL 2020;88:423-427.

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.

Akinetic mutism following prefrontal injury by an electrical grinder a case report: A diffusion tensor tractography study.

RATIONALE: A 72-year-old male had suffered from head trauma resulting from injury to his frontal area by an electrical grinder while working at his home. PATIENT CONCERNS: He lost consciousness for approximately 10 minutes and experienced continuous post-traumatic amnesia. DIAGNOSES: He was diagnosed as traumatic intracerebral hemorrhage in both frontal lobes, intraventricular hemorrhage, and subarachnoid hemorrhage, and underwent decompressive craniectomy and hematoma removal. INTERVENTIONS: The patient's Glasgow Coma Scale score was 5. At 2 months after onset, when starting rehabilitation, he showed no spontaneous movement or speech; he remained in a lying position all day with no spontaneous activity. OUTCOMES: On 2-month diffusion tensor tractography, decreased neural connectivity of the caudate nucleus to the medial prefrontal cortex (PFC, Broadmann area [BA]: 10 and 12) and orbitofrontal cortex (BA 11 and 13) was observed in both hemispheres. LESSONS: Akinetic mutism following prefrontal injury.

Ganser-like syndrome after loss of psychic self-activation syndrome: psychogenic or organic?

Very few data are available on the long-term changes in the cognitive abilities of patients with loss of psychic self-activation syndrome (LPSAS). Here, we present a 25-year follow-up study on a case of LPSAS resulting from bilateral pallidal lesions caused by carbon monoxide intoxication. Typical signs of LPSAS were observed, showing no changes in severity, but Ganser syndrome (GS) gradually developed and worsened during the follow-up period. GS is generally assumed to be a psychogenic syndrome, but an organic etiology has been suspected by the authors of several case reports. Here, atypical features of GS plead against the independence of GS and LPSAS. DaTSCAN and brain 18FDG-PET were performed. Since left hippocampal hypometabolism has been previously described in patients with functional amnesia, it is possible that long periods of mental inactivity may have psychological consequences, but the atypical features of GS also suggest that an organic mechanism may be involved.

Acute inferior homonymous quandrantanopia in a 71-year-old woman.

A 71-year-old woman presented with acute inferior homonymous quadrantanopia initially mimicking acute ischemic stroke. As clinical signs and symptoms progressed to akinetic mutism with myoclonus the diagnosis of the Heidenhain variant of Creutzfeldt-Jakob disease was made. Brain MRI 4 days after symptom onset revealed ribbon-like high signal intensity in the medial occipital cortex.

Delayed post-hypoxic leucoencephalopathy presenting akinetic mutism after traumatic cervical cord injury: a case report.

Delayed post-hypoxic leucoencephalopathy is a demyelinating syndrome characterized by acute onset of neuropsychiatric symptoms including parkinsonism or akinetic mutism that occurs days to weeks after recovery from cerebral hypo-oxygenation. We encountered a patient who presented with an akinetic mute state late after cervical cord injury without a definite hypoxic event.

Vegetative state, minimally conscious state, akinetic mutism and Parkinsonism as a continuum of recovery from disorders of consciousness: an exploratory and preliminary study.

The aim of this study was to review the usefulness of clinical and instrumental evaluation in individuals with disorders of consciousness (DOC). Thirteen subjects with severe acquired brain injury (ABI) and a diagnosis of DOC were evaluated using the Coma Recovery Scale in its revised version (CRS-R) and a new global disability index, the Post-Coma Scale (PCS). These instruments were administered both by a neutral examiner (professional) and by a professional in the presence of a caregiver. All patients were also scored using the International Classification of Functioning, Disability and Health (ICF). A statistically significant correlation between CRS-R and PCS was demonstrated. However, there also emerged significant differences in responsiveness between professional versus caregiver+professional assessment using the two scales. The emotional stimulation provided by significant others (caregivers) during administration of DOC evaluation scales may improve the assessment of responsiveness.

Delayed-onset diurnal bruxism, psychic akinesia and depression after carbon monoxide poisoning: a case report.

Diagnosing the delayed neuropsychological sequelae of carbon monoxide (CO) poisoning is a clinical challenge because of its varied presentations. Pallidal lesions, the most common site of involvement in CO poisoning [Clin Radiol. 2000;55(4):273-80] can cause psychic akinesia [Mov Disord. 2001;16(5):810-4; J Neurol Neurosurg Psychiatry 1984;47(4):377-85]. We present a patient with diurnal bruxism, psychic akinesia and depression that were delayed manifestations of CO poisoning.

The neurology of decreased activity: abulia.

Delirium is sometimes defined as acute onset of either overactivity or underactivity. This article reviews the nature and clinico-anatomical locations of lesions in patients with reduced activity. The term abulia is used to describe global underactivity. Abulia is customarily explained by interruptions in frontal-subcortical circuitry. These interruptions can occur with lesions in the frontal lobes, caudate nuclei, midbrain, and thalamus. The article describes the anatomy of frontal and subcortical circuits and reviews in detail individual cases and series of patients with reduced initiative and activity who have had localized central nervous system lesions.

Pathological subthalamic nucleus oscillations in PD: can they be the cause of bradykinesia and akinesia?

There is growing evidence that Parkinson's disease (PD) is associated with pathological synchronous oscillatory activity in the basal ganglia. These synchronized oscillations primarily occur in the 11-30 Hz range, the so-called beta band. Studies of local field potential activity in the subthalamic nucleus (STN) of PD patients suggest that exaggerated beta band oscillatory activity can disrupt function and, in particular, may contribute to slowness of movement. It has been previously shown that the degree of beta oscillatory activity in the STN of PD patients correlates with the patients' benefit from dopaminergic medications, but not with baseline motor deficits. In a paper that was recently published in Experimental Neurology, [Kuhn A.A., Tsui A., Aziz T., Ray N., Brucke C., Kupsch A., Schneider G.H., Brown P., 2009. Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity. Exp. Neurol. 215, 380-387.] the authors further establish that the degree of suppression of beta oscillations in the STN by dopaminergic medications can predict the level of improvement in bradykinesia and rigidity but not tremor. This commentary reviews some of the recent findings on beta oscillatory activity in PD and highlights the possible role of these pathological oscillations in mediating PD symptoms.

Akinetic mutism--not coma.

We describe a case of akinetic mutism mistaken as coma. A 77-year old lady presented with apparent unresponsiveness. In fact she responded when stimulated. She subsequently developed movements typical of clonic perseveration, erroneously treated as seizures. She also had features of a frontal lobe syndrome. Initial CT scan showed no abnormality; it was only after an MRI scan that a diagnosis of bilateral paramedian thalamic infarction was made. MRI scanning should be considered early in the investigation of patients with atypical neurological presentation.

Relationship between clinical course and Diffusion-weighted MRI findings in sporadic Creutzfeldt-Jakob Disease.

The aim of this study was to investigate the relationship between clinical course and diffusion-weighted MRI (DWI) findings in sporadic Creutzfeldt-Jakob Disease (sCJD). We reviewed clinical records and MRI examination in nine probable sCJD. According to hyperintense signal distribution on DWI, the patients were classified into two groups with cortical ribbon plus basal ganglia hyperintensity (6/9) and with only increased cortical signals (3/9). Clinical features including quadriparesis (3/6), akinetic mutism (2/6), and dysphasia (2/6), which were usually observed in the more advanced stage of CJD, were noted only in patients with cortical ribbon plus basal ganglia hyperintensity at the time of initial DWI examination. The patients with the cortical plus basal ganglia hyperintensity (6.4+/-1.7 weeks) had a shorter interval from symptom onset to akinetic mutism than those with only cortical ribbon hyperintensity (26.0+/-22.5 weeks) (p=0.02). These findings suggest that DWI may predict the clinical course of CJD.

Akinesia and the frontal lobe.

A report of severe akinetic episodes in patients with Parkinson disease (PD) has been the stimulus for the following discussion of akinesia and its variants. Severe persistent akinesia may occur in frontal lobe impairment. Therefore, it is likely that extension of the Parkinsonian dysfunction into the frontal lobe causes severe akinesia which should be separated from the very common Parkinsonian hypokinesia. Another very common clinical phenomenon of PD is sudden freezing. Hence the frontal lobe--hardly regarded as a region of special interest in the realm of PD--can be the cause of severe and dangerous complications of PD. The term "arrest reaction" or "motor arrest" denotes a similar freezing. It is recommended to restrict these terms to certain forms of frontal lobe epilepsy. This discussion of hypokinetic and akinetic states should also include catatonia: a form of schizophrenia with a special type of akinesia. Though without major neuropathological substratum, this condition can, in extremely rare cases, lead to severe hyperthermia and fatal outcome (presumably via hypothalamic dysfunction).

Inflammatory cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Sporadic Creutzfeldt-Jakob disease (CJD) is a fatal, transmissible spongiform encephalopathy characterized by rapidly progressive dementia, myoclonus, ataxia and akinetic mutism. The underlying mechanism is believed to be a conformational change of a native prion protein which characteristically fails to provoke an immune response. Commensurate with the latter, cerebrospinal fluid (CSF) classically exhibits a non-inflammatory profile. CASES: We report two patients with pathologically-proven sporadic CJD presenting with a significant CSF pleocytosis. CONCLUSION: Although uncommon, the presence of an inflammatory CSF profile should not exclude the diagnosis of sporadic CJD.