Transient Early Fine Motor Abnormalities in Infants Born to COVID-19 Mothers Are Associated With Placental Hypoxia and Ischemia

Background: Long-term effects of Coronavirus Disease 2019 (COVID-19) on infants born to infected mothers are not clear. Fine motor skills are crucial for the development of infant emotional regulation, learning ability and social skills.Methods: Clinical information of 100 infants born to 98 mothers (COVID-19 n = 31, non-COVID-19 n = 67) were collected. Infants were follow-up up to 9 months post-partum. The placental tissues were examined for SARS-CoV-2 infection, pathological changes, cytokines, and mtDNA content.Results: Decreased placental oxygen and nutrient transport capacity were found in infected pregnant women. Increased IL-2, IL-6, TNF-α, and IFN-γ were detected in trophoblast cells and maternal blood of COVID-19 placentas. Elevated early fine motor abnormal-ities and increased serum TNI (troponin I) levels at delivery were observed in infants born to mothers with COVID-19. Increased abnormal mitochondria and elevated mtDNA content were found in the placentas from infected mothers. The placental mtDNA content of three infants with abnormal DDST were increased by 4, 7, and 10%, respectively, compared to the mean of the COVID-19 group. The Maternal Vascular Malperfusion (MVM), elevated cytokines and increased placental mtDNA content in mothers with COVID-19 might be associated with transient early fine motor abnormalities in infants. These abnormalities are only temporary, and they could be corrected by daily training.Conclusions: Babies born to COVID-19 mothers with mild symptoms appeared to have little or no excess long-term risks of abnormal physical and neurobehavioral development as compared with the infants delivered by non-COVID-19 mothers.

Inhibition of Brain GTP Cyclohydrolase I Attenuates 3-Nitropropionic Acid-Induced Striatal Toxicity: Involvement of Mas Receptor/PI3k/Akt/CREB/ BDNF Axis

GTP cyclohydrolase I (GTPCH I) is the rate-limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis; the latter is an essential factor for iNOS activation that contributes neuronal loss in Huntington’s disease (HD). The aim of the study was to investigate the neuroprotective effect of 2,4-diamino-6-hydroxypyrimidine (DAHP), GTPCH I enzyme inhibitor, against neuronal loss in 3-nitropropinic acid (3-NP)-induced HD in rats and to reveal the possible involved mechanisms mediated through PI3K/Akt axis and its correlation to Mas receptor (MasR). Rats received 3-NP (10 mg/kg/day; i.p.) with or without administration of DAHP (0.5 g/kg/day; i.p.) or wortmannin (WM), a PI3K inhibitor, (15 μg/kg/day; i.v.) for 14 days. DAHP improved cognitive, memory, and motor abnormalities induced by 3-NP, as confirmed by striatal histopathological specimens and immunohistochemical examination of GFAP. Moreover, DAHP treatment inhibited GTPCH I activity, resulting in decreased BH4 levels and iNOS activation. Also, DAHP upregulated the protein expression of survival protein; p85/p55 (pY458/199)-PI3K and pS473-Akt that, in turn, boosted the activation of striatal neurotrophic factors and receptor, pS133-CREB, BDNF and pY515-TrKB, which positively affect MasR protein expression and improve mitochondrial dysfunction, as indicated by enhancing both SDH and PGC-1α levels. Indeed, DAHP attenuates oxidative stress by increasing SOD activity and Nrf2 expression in addition to reducing neuro-inflammatory status by inhibiting NF-κB p65 and TNF-α expression. Interestingly, all the previous effects were blocked by co-administration of WM with DAHP. In conclusion, DAHP exerts neuroprotective effect against neuronal loss induced by 3-NP administration via inhibition of GTPCH I and iNOS activity and activation of MasR/PI3K/Akt/CREB/BDNF/TrKB axis besides its antioxidant and anti-inflammatory effect.

A Neurologist's Practical Approach to Cognitive Impairment

The global prevalence of dementia is expected to triple by the year 2050. This impending health care crisis has led to new heights of public awareness and general concern regarding cognitive impairment. Subsequently, clinicians are seeing more and more people presenting with cognitive concerns. It is important that clinicians meet these concerns with a strategy promoting accurate diagnoses. We have diagramed and described a practical approach to cognitive impairment. Through an algorithmic approach, we determine the presence and severity of cognitive impairment, systematically evaluate domains of function, and use this information to determine the next steps in evaluation. We also discuss how to proceed when cognitive impairment is associated with motor abnormalities or rapid progression.

P.009 Improving Detection of Creutzfeldt-Jakob Disease Mimics in Clinical Practice

Background: Assays capable of detecting prions in CSF (e.g., RT-QuIC) have greatly improved the antemortem diagnosis of Creutzfeldt-Jakob disease (CJD) yet take time to conduct and are not widely accessible. There is a need to identify clinical features and common tests that identify mimics at presentation. Methods: Mimics were identified within longitudinal studies of rapidly progressive dementia at study sites. Mimics met clinical criteria for probable CJD but did not have CJD. Clinical features were compared between mimics and patients with CJD assessed at Mayo Clinic Enterprise (n=79) and Washington University in St. Louis (n=10; Jan-2014 to Oct-2020). Results: Mimics (10/155; 6.5%) were diagnosed with autoimmune encephalitis (n=7), neurosarcoidosis, frontotemporal lobar degeneration with motor neuron disease, and unknown dementia. Age-at-symptom onset, gender, presenting symptoms, and EEG and MRI findings were similar between mimics and CJD patients. Focal motor abnormalities (49/93, 10/10), elevations in CSF leukocytosis (4/92, 5/10) and protein (39/92, 9/10) were more common in mimics (p<0.01). Neural-specific autoantibodies associated with autoimmune encephalitis were detected within the serum (4/9) and CSF (5/10) of mimics, but not CJD cases. Conclusions: Autoimmune encephalitis, neurosarcoidosis and neurodegenerative diseases may mimic CJD at presentation and should be considered in patients with early motor dysfunction and abnormal CSF studies.

Catatonia: A Common Cause of Late Regression in Autism

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and restricted interests and behaviors which begin very early in life. In about a quarter of cases, the symptoms emerge about 18–24 months after a period of normal development, a phenomenon commonly described as early regression. However, marked functional decline can also occur in persons with autism after a relatively stable childhood. As opposed to early regression, which occurs in normally developing children, late regression occurs typically in adolescents with an established diagnosis of autism. Apart from their occasional mention in the literature, these individuals have not been examined systematically. This Brief Report describes the presentation, comorbidity and short-term outcome of 20 persons with ASD who developed late regression. The mean age of onset of regression was 13 years. One of the earliest symptoms was an increase in obsessive slowing and compulsive rituals. Other symptoms included motor abnormalities, aggression and mood disturbance. The most common comorbid disorder was catatonia occurring in 17 patients. Despite treatment with several modalities, the outcome was often suboptimal. These findings suggest that catatonia is a common cause of late regression in persons with autism. Clinical and research implications are discussed.

Contactless In-Home Monitoring of the Long-Term Respiratory and Behavioral Phenotypes in Older Adults With COVID-19: A Case Series

Currently, there is a limited understanding of long-term outcomes of COVID-19, and a need for in-home measurements of patients through the whole course of their disease. We study a novel approach for monitoring the long-term trajectories of respiratory and behavioral symptoms of COVID-19 patients at home. We use a sensor that analyzes the radio signals in the room to infer patients' respiration, sleep and activities in a passive and contactless manner. We report the results of continuous monitoring of three residents of an assisted living facility for 3 months, through the course of their disease and subsequent recovery. In total, we collected 4,358 measurements of gait speed, 294 nights of sleep, and 3,056 h of respiration. The data shows differences in the respiration signals between asymptomatic and symptomatic patients. Longitudinally, we note sleep and motor abnormalities that persisted for months after becoming COVID negative. Our study represents a novel phenotyping of the respiratory and behavioral trajectories of COVID recovery, and suggests that the two may be integral components of the COVID-19 syndrome. It further provides a proof-of-concept that contactless passive sensors may uniquely facilitate studying detailed longitudinal outcomes of COVID-19, particularly among older adults.