COVID19

Review of literature: introduction and clinical presentations of COVID19

Review of literature: introduction to the COVID19 and clinical presentations

credit: photo by CDC by Unsplash

Virginia Thornley, M.D.
Neurologist
April 2, 2020

Introduction
A new virus emerged in Wuhun, China in December 2019. But the information is still emerging on how to treat it and the exact pathophysiology.

The coronavirus is a type of virus that can infect both animals and humans.
It was named COVID19 for corona virus disease 2019 and renamed SARS-CoV2 which was discovered in the epithelium of the respiratory system of patients from Wuhun, China (1).

COVID-19
COVID19 first occurred December 7, 2019 in the markets of Wuhun, China. The pathogen is the SAR-CoV2. The intermediate host is thought to be the Pangolin. It is a type of RNA virus. The original host is an animal but it jumped to humans. The species pathogen is the B-corona virus. The latency period is about 2-7 days infecting people who have never been exposed to it before(1).

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Clinical presentation
The infection is classified as mild, moderate, severe and critical. Mild cases present with fever, respiratory symptoms and no pneumonia on imaging studies. Moderate is described as those with fever, respiratory symptoms and pneumonia on imaging studies. Severe cases present with respiratory failure with a respiratory rate greater than 30/minute, oxygen saturation or O2 saturation of less than or equal to 93mmHg, PaO2/FiO2 of less than 300mmHg. Critical cases include one of the following: need for mechanical ventilation, shock or organ failure requiring ICU admission. There can be dyspnea leading to acute respiratory distress syndrome (ARDS), metabolic abnormalities that are refractory to correction, shock and coagulopathy (3).

Epidemiology
The SARS epidemic which occurred in 2003 affecting China extending to other other Southeast Asian countries, by contrast, lasted 7 months affecting 8096 people resulting in 774 deaths. There was a high mortality rate among hospital personnel of about 21% (1). The COVID19 started December 7, 2019 and is still ongoing at the time of this writing. At the time of this writing, there are 1,040617 affected with 55,188 deaths(2). The numbers continue to climb. It was declared a pandemic by the WHO. Most clinical cases are elderly, however, the coronavirus could be seen in those with diabetes mellitus and hepatitis B. An immunocompromised state is also a risk factor. Male to female ratio based on studies in China is 2.7:1. Mortality rate is 2.1%

References:
1. Xu, J., Zhao, S., Teng, T., Abdalla, A.E., Zhu, W., XIE, L., Wang, Y., Guo, X. Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV. Viruses. 2020, Feb. 22;12(2).
2. Worldometer, Coronavurus pandemic 2019
3. Feng, Y., Liu, N., Hu, J., Wu, l., Su, G., Zhong, N., Zheng, Z. 4S Respiratory rehabilitation guidelines for patients with pneumonia infected by new Coronavirus. Chinese Journal of Tuberculosis and Respiratory Diseases, 2020, 43: Pre-published online. DOI: 10.3760 / cma.j.issn.1001-0939.2020.0004

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PRP

Platelet-rich plasma and mechanism of action

Virginia Thornley, M.D., Neurologist
January 26, 2020

Introduction
Pain is one of the most common conditions that brings a patient to see a physician. Pain is a sign of dysfunction, something is not quite right. There is a plethora of research devoted to understanding the mechanisms.

Some of the more novel approaches are platelet-rich plasma and stem cell therapy. Currently, it is not FDA approved in the United States. It is a novel approach used more extensively outside of the United States.

Mechanism of action
PRP has several growth factors that helps with pain one of which is platelet derived growth factor (PDGF). PDGF arises in the setting of injury when platelets are degranulated. It activates cells which develop high phosphate bonds which leads to specific activities. These activities include mitogenesis, angiogensis and stimulation of macrophage activity. Other growth factors include TGF-beta or transforming growth factor-beta. The target cells are pre-osteoblasts, fibroblasts and marrow stem cells. VEGF or vascular endothelial growth factor is found which stimulates angiogenesis or the formation of new blood vessels. EGF or epidermal growth factor stimulates growth of cells, proliferation and differentiation (1).

Indications
It was found to be helpful in helping injured ligaments and tendons in sports injury.
In one study of 22 patients with intradiscal pain, PRP intradiscal injections were performed which showed encouraging results (2). There are many other indications for PRP in terms of pain control for other conditions.

Summary
PRP shows promising results for various types of pain which was initially used in sports medicine injury but is now expanding to other areas. Large randomized-controlled clinical trials are still needed. However, it is still a viable option. More studies are needed.


References
Jain., N.K., Gulati, M, Platelet-rich plasma: a healing virtuoso, Blood Res. 2016 Mar; 51(1):3-5.
Levi, D., Horn, S., Tyszko, S., Levin, J., Hecht-Leavitt, C., Walko, E., Intradiscal platelet-rich plasma injection for chronic discogenic low back pain: preliminary results from a prospective trial, Pain Med. 2016, Jun; 17(6):1010-1022.

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neurology

Can anti-psychotic agents reduce brain volume?

Virginia Thornley, M.D.
Neurologist, Epileptologist
October 9, 2019
Can medications cause cerebral atrophy? Atrophy refers to shrinkage of the cells causing the appearance of the brain to have less volume than usual.
This question was asked last week. Anti-epileptics such as phenytoin is well-known in the literature and clinically to cause cerebellar atrophy. But what about other agents such as anti-psychotics.
Animal studies
In one animal study, exposure to anti-psychotic drugs showed a reduced volume of brain on volumetric studies. The number of cells remained the same but the volume was increased for cells in the anterior cingulate gyrus which is in the  limbic lobe. The limbic lobe subserves emotions and has influence on memory. Animal studies do not always correlate with human responses.
Human studies
One small study showed that the thalamic volume was reduced after olanzepine administration. This was a small study of 10 patients (2).
While there is some information in the literature the studies are animal studies and small human studies. More information is needed. Based on the current literature, there are not enough significant studies to correlate atrophy with use of anti-psychotics.
References
  1. Vernon, A.C., Crum, W.R., Lerch, J.P., Chege, W., Natesan, S., Modo, M., Cooper, J.D., Williams, S.C., Kapur, S. Reduced cortical volume and elevated astrocyte density in rats chronically treated with anti-psychotic drugs-linking magentic resonance imaging findings to cellular pathology. Biol Psychiatry. 2014, Jun. 15, 75(12):982-90
  2. Khorram, B., Lang, D.J., Kopala, L.C., Vandorpe, RF.A., Rui, Q., Goghari, V.M., Smith, G.N., Honer, W.G. Reduced thalamic volume in patients with chronic schizophrenia after switching from typical anti-psychotic medications to olanzepine. Am J sychiatry. 2006, Nov. 163 (11):2005-7
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dementia

Animal study demonstrating CBD’s (cannabidiol) effects on neuroplasticity and memory loss

Virginia Thornley, M.D.
Neurologist, Epileptologist
August 26, 2019
In an animal study, one group demonstrates that Cannabidiol may help with the neuroplasticity in patients with Alzheimer’s disease (1).
LTP in the hippocampus is the long-term potentiation seen that elevates the efficacy of synapses involved in memory. Beta-amyloid peptide is toxic towards this  feature. When animals were pretreated with CBD the neurotoxicity was found to be reduced against beta-amyloid peptide. The same study showed that it did not involve the 5-HT1a, CB1 or adenosine receptors (1).
There have been other previous studies showing that cannabidiol could have protective effects against the toxic effects of beta-amyloid peptide which is involved in the neurodegenerative process seen in Alzheimer’s disease.
More clinical randomized control trials are needed. Animal studies do not always translate into human studies.
Neurologybuzz.com
References
  1. Hughes, B., Herron, C.E., Cannabidiol reverses deficits in hippocampal LTP in a model of Alzheimer’s disease. Neurochem. Res. 2019, Mar. 44(3):703-713

This is medical information not medical advice. Please consult with your physician.

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multiple sclerosis, Uncategorized

The impact of immunomodulating agents used in multiple sclerosis on the risk of cancer

Virginia Thornley, M.D., Neurologist, Epileptologist
June 14, 2019
Introduction
Multiple sclerosis is already an illness where the immune system recognizes the nervous system specifically the white matter tracts as foreign and attacks it. The complex cascade of mechanisms make adequate treatment challenging. Many treatments focus on the inflammatory mechanism with little attention on the degenerative mechanism involved.
Presentation of symptoms come in a wide variety depending on the the location of the multiple sclerosis plaque in the brain.
Patients may have concomitant morbidities which may make treatment challenging.
 
Immunomodulating agents and its impact on cancer
Many of the newer treatments for multiple sclerosis work at the level of the immune system through immunosuppression, the newer ones tend to be very potent. With greater efficacy comes greater risks including the risk of cancer.
Some of the newer medications can potentially increase the risk of cancer. Higher risk of cancer was found in many reports to occur with use of cyclophosphamide, azathioprine and mitoxanthrone. Fingolimod, natalizumab and alemtuzamab  can potentially increase the risk of cancer, these agents lack long-term data and work through the immune system. Dimethyl fumarate, terifluonimide, ocrelizumab, daclizumab and cladribine merit mandatory risk management plans to detect cancer before its use.
Reference
  1. Lebrun, C., Rocher, F., Cancer risk in patients with multiple sclerosis: potential impact of disease-modifying drugs. CNS Drugs. 2018, Oct. 32(10):939-949 doi:10.1007/s40263-018-0564-y
Disclaimer: This is medical information only not medical advice. Please consult your physician
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cerebellar ataxia

Genetics of Hereditary Cerebellar Ataxia and Hereditary Spastic Paraplegia

Virginia Thornley, M.D.
Neurologist, Epileptologist
March 18, 2019
Introduction
Cerebellar ataxias are rare disorders, only a few types are treatable. This reviews some of the research regarding the genetics of cerebellar ataxias.
Next generation sequencing is a revolutionary way of DNA sequencing that can sequence an entire genome in one day which previously took 10 years. Clinical applications are still pending (1).
Genetics of hereditary cerebellar ataxias
In one study of 87 patients, the genetics were studies. In the probands meaning the first in a genetic line, triplet repeat testing was done. 58% were male. Genetic variants included ANO10, CACNA1A, SPG7 and DRKCG. The detection rate in probands for the trinucleotide repeat was about 13.8%. Those with variants may have a longer duration of disease and a slower progression of the disorder (2).
 
Genetic testing in hereditary spastic paraparesis
In another study where 306 were genetically tested, next generation sequence testing was performed and different genes were found. These include ATL1 (atlastin 1, SPG3),
PAST (spastin, SPG4),  ITPR1, WASHC5 (SPG8),  KIF1A (SPG30), SPG11 spastacsin), KIF5A (SPG10), CYP27A1, and SETX (3).
There are overlapping genetics and clinical symptoms with spinocerebellar ataxia and amyotrophic lateral sclerosis.
Reference
  1. Behjati, S., Tarpey, P., What is next generation sequencing? Arch Dis Child Educ Pract Ed. 2013 Dec; 98(6)236-238
  2. Kang, C., Liang, C., Ahmad, K.E., Gu, Y., Siow, S.F., Colebatch, J.G., Whyte, S., N, K., Cremer, P.D., Corbett, A.J., Davis, R.L., Roscioloi, T., Cowley, M.J., Park, S.J., Sue, C.M., Kumar, K.R. High Degree of Genetic Hetereogeneity for Hereditary Cerebellar Ataxias in Australia, Cerebellum, 2019, Feb. (1):137-146
  3. Elert-Dobkowska, E., Stepniak, I., Krysa, W., Ziora-Jakutowicz, K., Rakowicz, M., Sobanska, A., Pilch, J., Antczak-Marach, D., Zaremba, J., Sulek, A. Next-generation sequencing reveals the broader variant spectrum of hereditary spastic paraplegia and related phenotypes. Neurogenetic, 2019, Feb, doi:10.1007/s10048-019-00565-6
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