Is the Frontal Lobe the Primary Target of SARS-CoV-2?

Acute delirium and other neuropsychiatric symptoms have frequently been reported in COVID-19 patients and are variably referred to as acute encephalopathy, COVID-19 encephalopathy, SARS-CoV-2 encephalitis, or steroid-responsive encephalitis. COVID-19 specific biomarkers of cognitive impairment are currently lacking, but there is some evidence that SARS-CoV-2 could preferentially and directly target the frontal lobes, as suggested by behavioral and dysexecutive symptoms, fronto-temporal hypoperfusion on MRI, EEG slowing in frontal regions, and frontal hypometabolism on 18F-FDG-PET imaging. We suggest that an inflammatory parainfectious process targeting preferentially the frontal lobes (and/or frontal networks) could be the underlying cause of these shared clinical, neurophysiological, and imaging findings in COVID-19 patients. We explore the biological mechanisms and the clinical biomarkers that might underlie such disruption of frontal circuits and highlight the need of standardized diagnostic procedures to be applied when investigating patients with these clinical findings. We also suggest the use of a unique label, to increase comparability across studies.

Detailed clinical course of fatal acute encephalopathy in children.

OBJECTIVE: Although the mortality among previously healthy children with acute encephalopathy (AE) is approximately 5%, their detailed clinical course has not been clarified. The objective of the present study was to describe the detailed clinical course, in minutes, of fatal AE. METHODS: We retrospectively reviewed the medical records of five patients (from 6 months to 14 years of age) who previously had no neurological disorders and were diagnosed with brain death due to AE between 2002 and 2018 at Kobe Children's Hospital. RESULTS: The initial clinical symptoms were convulsion in three cases and impaired consciousness in two. The earliest noted brain imaging abnormality was 7.5 h after neurological symptom detection. Liver enzymes and creatinine levels increased at initial examination, and sodium elevated gradually. All patients met the criteria of systemic inflammatory response syndrome, disseminated intravascular coagulation, and shock within 14 h of symptom detection. High dose steroids and targeted temperature management were initiated 3.5-14 h after onset. Despite these therapies, patients were diagnosed with brain death from 16 h to 4 days after initial neurological symptoms. AE diagnoses were made between 4 h 29 min and 4 days after initial neurological symptoms and included hemorrhagic shock and encephalopathy syndromes, Reye-like syndrome, and acute necrotizing encephalopathy in two, two, and one patient(s), respectively. CONCLUSIONS: We revealed the time series' of clinical events (e.g. SIRS, shock, DIC, AE diagnosis, brain death, and treatments) and laboratory findings relative to initial neurological symptom in fatal AE.

Developing a mouse model of acute encephalopathy using low-dose lipopolysaccharide injection and hyperthermia treatment.

IMPACT STATEMENT: Acute encephalopathy (AE), mainly reported in East Asia, is classified into four categories based on clinical and neuropathological findings. Among them, AE caused by cytokine storm is known as the severest clinical entity that causes cerebral edema with poor prognosis. Because suitable and convenient model animal of AE had not been developed, the treatment of patients with AE is not established. In the present study, we established a simple and convenient protocol to mimic AE due to cytokine storm. Our model animal should be useful to elucidate the pathogenesis of AE.

Profile of Pediatric Scrub Typhus in Odisha, India.

OBJECTIVE: To investigate the distribution and clinical profile of scrub typhus infection among children with acute febrile illness in Odisha. METHODS: Children (<15 y) presenting with acute fever (>5 days) in 4 agro-climatic zones from June to November 2017 were evaluated. Patients were screened for malaria, leptospira, dengue, typhoid and scrub typhus. Scrub typhus was confirmed by IgM ELISA and PCR. RESULTS: Out of 413 cases examined, 48.7% were positive for scrub typhus, and 5.5% of them developed systemic complications. Eschar was found in 17.9% of cases. Five days treatment of Doxycycline and/or Azithromycin was clinically effective against scrub typhus. CONCLUSIONS: Our study highlights that scrub typhus is one of the causes of high morbidity in children during rainy months in Odisha.

Early ictal and interictal patterns in FIRES: The sparks before the blaze.

OBJECTIVE: Febrile infection-related epilepsy syndrome (FIRES) is a catastrophic epileptic encephalopathy described as explosive onset of super refractory status epilepticus (SRSE) in previously healthy children. We describe electroencephalography (EEG) abnormalities in the hyperacute phase of FIRES, with the aim of contributing to the diagnostic characterization of a syndrome otherwise lacking specific biomarkers. METHODS: This is a retrospective single-center, case series of seven children with FIRES. Cases were identified from a Neurocritical Care database. Patient characteristics and clinical course were obtained from electronic medical records. Electroencephalography recordings were reviewed in two segments: the initial 12 h of recording and the 12 h prior to initiation of a medically induced burst suppression (BS). RESULTS: Fourteen 12-h segments of video-electroencephalography (EEG) recordings were analyzed for commonalities. A beta-delta complex resembling extreme delta brush (EDB) occurred in at least one 12-h segment for all patients. In six patients, seizures were brief and relatively infrequent during the first recording, with a gradual evolution to status epilepticus by the second. We observed a characteristic electrographic seizure pattern in six of seven patients with prolonged focal fast activity at onset. Shifting seizures were seen in four of seven patients. SIGNIFICANCE: The diagnosis of FIRES is typically assigned late in a patient's clinical course, which has broad implications for clinical care and research. We retrospectively analyzed acute EEG features in seven patients with FIRES and discovered three common features: gradual increase in seizure burden, presence of a recurrent EDB, and a typical seizure pattern. Recognition of this pattern may facilitate early diagnosis and treatment.

Acute encephalopathy in a 2-year-old pot-bellied pig following accidental intoxication with clonazepam.

OBJECTIVE: To describe a case of successful management of clonazepam toxicity causing encephalopathy in a pot-bellied pig. CASE SUMMARY: A 2-year-old female pot-bellied pig weighing 13.5 kg was presented for evaluation of clinical signs of acute encephalopathy. Based on the animal's history and clinical signs, a tentative diagnosis of benzodiazepine (BZP) intoxication was made. The results of a urinary drug screening test designed to detect illicit substances in human urine indicated benzodiazepine exposure. Gas chromatography and mass spectrometry analysis later confirmed clonazepam (urinary concentration 496 ng/mL) as the intoxicating substance. The pig responded favorably to treatment which included administration of flumazenil, decontamination with enteral activated charcoal, and intravenous isotonic crystalloid administration. The pig had a rapid improvement in mentation 10 minutes following IV flumazenil administration and was considered mentally appropriate following 24 hours of hospitalization. The pig was discharged from the hospital after 48 hours of care, and was reported to be doing well 6 months later. NEW INFORMATION PROVIDED: Intoxication with prescription benzodiazepines can occur in companion animals and result in clinical signs of acute encephalopathy. Urinary drug screening tests designed for human use may provide rapid results to indicate drug intoxication and guide therapeutic intervention in veterinary species. Administration of flumazenil resulted in a rapid improvement in mentation following clonazepam intoxication in a pot-bellied pig.

A case of acute encephalopathy with biphasic seizures and late reduced diffusion: Utility of arterial spin labeling sequence.

A 1-year-old boy was admitted because of febrile status epilepticus (FSE). A secondary cluster of seizures was seen on day 5 after onset, and the patient eventually displayed developmental delay. Conventional magnetic resonance imaging (MRI) showed no abnormal findings on day 1 after onset, but showed reduced diffusion in the subcortical regions of bilateral frontal lobes on day 5 after onset. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was diagnosed. Arterial spin labeling (ASL) revealed reduced cerebral blood flow (CBF) in bilateral frontal lobes on day 1 after onset and showed increased CBF in the corresponding region in the subacute phase. Outcomes after prolonged febrile seizures are usually good, but mental deficit and/or epilepsy often remain in AESD. Discriminating between these syndromes is difficult, because no useful biomarkers have been identified. Reduced CBF in bilateral frontal lobes was observed on ASL on day 1 of FSE in the present case, and this finding may be predictive of developing AESD.