Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007758 (cerebellar ataxia)
 3,609 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The current worldwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that causes coronavirus disease 2019 (COVID-19) has brought some medical systems to the brink of collapse. This crisis is also negatively impacting the care of patients with non-COVID-19 conditions, including those with cerebellar ataxia (CA). Older patients with CA and those with immune-mediated ataxias on immunosuppressive medication are potentially at high risk of developing serious complications of the infection, although it is also possible that immunosuppressive agents may provide a defense against cytokine storm. This has implications for even greater attention to preventing contracting the disease through physical distancing and/or isolation. The CA patient population is also at higher risk because of the neurological complexities of their underlying disorder and the comorbid medical illnesses that often accompany the genetic ataxias. As the disruption of social patterns and healthcare delivery in response to the crisis continues, interruption of rehabilitation, speech and language therapy, and face-to-face consultations threatens to have a negative impact on the course and well-being of CA patients. Mental and physical health is also potentially at greater risk because the prevailing uncertainty and anxiety may be superimposed upon cerebellum-specific neuropsychological challenges. We identify and review some of the short- and long-term consequences of this global pandemic for the community of ataxia patients and their families and for the clinical and academic neurologists/ataxiologists caring for these patients. This includes the recognition that telemedicine has emerged as a principle means of caregiver-patient contact and that neurological manifestations of COVID-19 including those specific to cerebellar neurobiology are increasingly recognized and will require close surveillance and monitoring. This COVID-19 Cerebellum Task Force consensus provides some guidance on how we may approach this uncertain time and consider preparing for the new realities we face in CA patient care once this acute crisis has passed.
 ...
PMID:Management of Patients with Cerebellar Ataxia During the COVID-19 Pandemic: Current Concerns and Future Implications. 3240 55

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the cause of the current pandemic coronavirus disease 2019 (COVID-19), primarily targets the respiratory system. Some patients also experience neurological signs and symptoms ranging from anosmia, ageusia, headache, nausea, and vomiting to confusion, encephalitis, and stroke. Approximately 36% of those with severe COVID-19 experience neurological complications. The virus may enter the central nervous system through the olfactory nerve in the nasal cavity and damage neurons in the brainstem nuclei involved in the regulation of respiration. Patients with cerebellar ataxia (CA) are particularly vulnerable to severe outcome if they contract COVID-19 because of the complexity of their disease, the presence of comorbidities, and their use of immunosuppressive therapies. Most CA patients burdened by progressive neurologic deficits have substantially impaired mobility and other essential functions, for which they rely heavily on ambulatory services, including rehabilitation and psychosocial care. Cessation of these interventions because of isolation restrictions places the CA patient population at risk of further deterioration. This international panel of ataxia experts provides recommendations for neurologists caring for patients with CA, emphasizing a pro-active approach designed to maintain their autonomy and well-being: continue long-term medications, promote rehabilitation efforts, utilize the technology of virtual visits for regular contact with healthcare providers, and pay attention to emotional and psychosocial health. Neurologists should play an active role in decision-making in those CA cases requiring escalation to intensive care and resuscitation. Multi-disciplinary collaboration between care teams is always important, and never more so than in the context of the current pandemic.
 ...
PMID:Medical and Paramedical Care of Patients With Cerebellar Ataxia During the COVID-19 Outbreak: Seven Practical Recommendations of the COVID 19 Cerebellum Task Force. 3257 47

ACE2 is a type I membrane protein with extracellular carboxypeptidase activity displaying a broad tissue distribution with highest expression levels at the brush border membrane (BBM) of small intestine enterocytes and a lower expression in stomach and colon. In small intestinal mucosa, ACE2 mRNA expression appears to increase with age and to display higher levels in patients taking ACE-inhibitors (ACE-I). There, ACE2 protein heterodimerizes with the neutral amino acid transporter Broad neutral Amino acid Transporter 1 (B0AT1) (SLC6A19) or the imino acid transporter Sodium-dependent Imino Transporter 1 (SIT1) (SLC6A20), associations that are required for the surface expression of these transport proteins. These heterodimers can form quaternary structures able to function as binding sites for SARS-CoV-2 spike glycoproteins. The heterodimerization of the carboxypeptidase ACE2 with B0AT1 is suggested to favor the direct supply of substrate amino acids to the transporter, but whether this association impacts the ability of ACE2 to mediate viral infection is not known. B0AT1 mutations cause Hartnup disorder, a condition characterized by neutral aminoaciduria and, in some cases, pellagra-like symptoms, such as photosensitive rash, diarrhea, and cerebellar ataxia. Correspondingly, the lack of ACE2 and the concurrent absence of B0AT1 expression in small intestine causes a decrease in l-tryptophan absorption, niacin deficiency, decreased intestinal antimicrobial peptide production, and increased susceptibility to inflammatory bowel disease (IBD) in mice. Thus, the abundant expression of ACE2 in small intestine and its association with amino acid transporters appears to play a crucial role for the digestion of peptides and the absorption of amino acids and, thereby, for the maintenance of structural and functional gut integrity.
 ...
PMID:ACE2 and gut amino acid transport. 3314 Aug 27