COVID19

Anosmia and ageusia as clinical manifestations of COVID-19

Anosmia and ageusia as clinical manifestation of COVID-19
Virginia Thornley, M.D.s
Neurologist
April 24, 2020

photo credit CDC by Unsplash
Neurologybuzz.com
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Introduction
COVID-19 can present with a variety of symptoms and is not necessarily limited to fever and respiratory symptoms. As the pandemic continues, more observations of the wide spectrum of clinical presentations are seen. Two of these are anosmia and ageusia-loss of smell and taste.

Studies
A very recent study came out April 22, 2020, comparing patients with COVID-19 and influenza with 79 cases including 40 controls. New onset smell and taste disorders (STD) were found to be more common as initial clinical symptoms compared to controls with influenza (1). In the group with COVID-19, 35% had acute onset as the first symptom, 70% had loss of smell, 90% had loss of taste, and 12.9% had nasal obstruction. 40% recovered after 7.4 days(1).

Anosmia or lack of smell has been reported in several countries U.K., France, United States, South Korea, Italy and Iran (2).

There are case reports on 2 patients with COVID-19 infection one who died, showing anosmia in the absence of respiratory symptoms. It is thought to be related to inflammation of the olfactory nerves (3).

Conclusion
There are now randomized controlled clinical studies showing that anosmia and ageusia can be an initial clinical symptom of COVID-19. There are case reports that it can be the only symptom.


Disclaimer: Information only not advice talk to your doctor.
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References
1. Beltram-Corbelliini, A., Chico-Garcia, J.L, Martinez-Poles, J., Rodrigiez-Jorge, F., Natera-Villalba, E., Gomez,Corral, J., Gomez-Lopez, A., Monreal, E., Parrra-Diaz, P., Cortes-Cuevas, J.L, Galan, J.C., Fragola-Arnau, C., Porta-Etessam, J., Masjuan, Alonso-Canovas, A., Acute-onset small and taste disorder in the context of COVID-19: a pilot multi-center PCR-based case-control study. Eur J Neurol 2020 Apr 22. doi: 10.1111/ene.14273
2. Heidari, F., Karimi, E., Firouzifar, M., Khamushian, P., Ansari, R., Mohammed Ardehali, Heidari, F. Rhinology, 2020, Apr 22. doi: 10.4193/Rhin20.140
3. Villalba, N.L., Maouche, Y., Ortiz, M.B.A., Sosa, Z.C., Chahbazia, J.B., Syrovatkova, A., Pertoldi, P., Andres, E., Abrar-Ahmed, Z, Anosmia and dysgeusia in the absence of other respiratory diseases: should COVID-19 infection be considered? Eur J Case Rep Intern Med. 2020. 7(4):001641 doi: 10.12890/2020_001641

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COVID19

A review of the literature: cytokine storm in COVID-19 and novel treatments and trials

Virginia Thornley, M.D.
Neurologist
April 13, 2020

Neurologybuzz.com
http://virginiathornleymd.com/

Introduction
COVID-19 is now a global pandemic. The world is in the midst of a virus that is still an unknown entity. Here, we look at the published research of what we know so far.

Cytokine storm
COVID-19 or the coronavirus is thought to incite a cytokine storm. On review of the literature for severe influenza, a cytokine storm refers to the release of cytokine factors triggered by infection or drugs. It is caused by the breakdown of infected white blood cells through apoptosis causing the release of cytokine factors that lead to a release of even more white blood cells. First, there are infected white blood cells then pro-inflammatory cytokines react. These lead to increased expression of anti-viral, proinflammatory apoptotic genes resulting in tissue damage. There are simultaneous regenerative processes occurring. Usually, the repair is complete. In some cases, it results in severe tissue damage and excess inflammatory responses resulting in alveolar damage. The excessive cytokine-induced inflammation can leak systemically resulting in widespread organ failure (1).

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photo credit: CDC through Unsplash

Therapies including IL-6 inhibitors and convalescent plasma
In one report, there is some treatment targeting the cytokine storm which is thought to make some progress including interleukin-6 (IL-6) antibody inhibitors, stem cell therapy as well as transfusion of plasma in convalescence(2). Currently, there are clinical trials at Mount Sinai Hospital in New York City to look into the use of convalescent plasma. There are ongoing trials for interleukin-6 inhibitors by drug companies Sanofi and Regeneron.

Chloroquine
While chloroquine is recommended by expert Chinese consensus after extensive discussion, there are, however, no large human randomized controlled clinical trials yet in COVID-19 showing sufficient scientific evidence that it definitively works(3). Many clinical studies for drugs are ongoing at the time of this writing.

NSAIDs and COVID-19
While there are no studies specifically on the effect of non-steroidal anti-inflammatory drugs on COVID-19, however, there are suggestions it could potentially blunt the immune system from fighting the virus (4). In a UK publication in the BMJ 2020, doctors and scientists believe that NSAIDs in the setting of respiratory failure in COVID-19 could potentially lengthen the time of recovery. Thoughts are that the respiratory illness may be prolonged with the use of NSAIDs. This stemmed from a comment made by an infectious disease doctor in the south of France where 4 individuals with COVID-19 appeared to worsen with the inclusion of NSAIDs in the treatment protocol. Ibuprofen was deleted from treatment protocols in patients with infections in France as of 2019 with paracetamol used in its place. This was supported by expert figures in the UK (4).

Hydroxychloroquine and azithromycin
One small study of 20 patients was recently published showing some improvement of patients on a combination of hydroxychloroquine and azithromycin (5).

Summary
Because this is a novel virus, research is still ongoing and fluid. Larger human studies are needed. There are larger trials ongoing for various drugs. So far most of the research that has been published is in a small number of patients.

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Disclaimer: This is information only not advice, please consult with your physician

References
1. Liu, Q., Zhou, Y. & Yang, Z. The cytokine storm of severe influenza and the development of immunomodulatory therapy. Cell Mol Immunol 13, 3–10 (2016). https://doi.org/10.1038/cmi.2015.74
2.Chen, C., Zheng, X.R., Ju, Z.Y., He, WF. Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies. Zhonghua Shao Shang Za Zhi. 2020 Mar. 1;36(0):E005
3.Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):185-188. doi: 10.3760/cma.j.issn.1001-0939.2020.03.009.
4. BMJ 2020;368:m1086 doi: 10.1136/bmj.m1086
5. Gautret, P., Lagier, J., Parola, P., Hoang, V.T., Meddeb, L., Mailhe, M., Doudier, B., Courion, J., Giordanengo, V., Viera, V., Dupont, H., Honore, S., Colson, P., Chabriere, E.,La Scola, B., Rolain, J., Brouqui, P., Raoult, D. Hydroxychloroquine and azithromycin as a treatment of COVD-19: results of an open-label non-randomized clinical trial, Int. J. Antimicrobi Agents. 2020, Mar 20doi: 10.1016/j.ijantimicag.2020.105949 [Epub ahead of print]

Disclaimer: This is information only not advice, please consult with your physician

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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 thrombosis(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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Essential tremor, Uncategorized

Deep brain stimulation and essential tremor

Virginia Thornley, M.D.
Neurologist, Epileptologist
November 6, 2019
Essential tremor is now treated with implantation of a deep brain stimulating device. It has been approved for treatment for Parkinson’s disease, essential tremor, dystonic tremor and obsessive compulsive disorder (1).
Basically, within the brain, there is a recurrent loop that is not inhibited by the correct feedback inhibition resulting in repetitive actions. In obsessive-compulsive disorders, there are repetitive thoughts and actions since this loop is not controlled.
In one study, the ventral intermediate nucleus (VIM) was stimulated in 98 patients with Parkinson’s disease, essential tremor and dystonic tremor with sustained improvement. There was significant long-term improvement even after 10 years(2).
The mechanism is unclear. However, certain nuclei stimulated were found to result in side effects. Thalamic stimulation resulted in fatigue. Subthalamic nuclear implantation was found to give rise to depression and suicidality(3).
Neurologybuzz.com
References
  1. Naestromm, M., Blomstedt, P., Hariz, M., Bodjund, O., Deep brain stimulation for obsessive-compulsive disorder: knowledge and concerns among psychiatrists, psychotherapists and patients,  Surg. Neurol Int. 2017; 8:298 
  2. Cury, R.G., Fraix, V., Castrioto, A.,Perez-Fernandez, M.A., Krack, P., Chabardes, S., Seigneuret, E., Alho, E.J., Benabid, A.L., Moro, E. Thalamic deep brain stimulation in Parkinson disease, essential tremor and dystonia. Neurology. 2017 Sep 26;89(13):1416-1423
  3. Zarzycki, M.Z., Domitrz, I., Stimulation-induced side effects after deep brain stimulation-a systematic review. Acta Neuropsychiatr. 2019, Aug 27:1-24
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Anxiety

Do anti-depressants or anxiolytics cause lower levels of vitamins and minerals?

Virginia Thornley, M.D., Neurologist, Epileptologist
November 4, 2019
A recent question prompted this literature search. We know that patients ho are depressed often complain of fatigue. But which came first the chicken or the egg?
Fatigue could be a result from not sleeping well due persistent thoughts and rumination at night. But can long-term anti-depressants and anxiolytics cause a lowering of vitamins and minerals leading to fatigue? We search the literature.
In one meta-analysis, folate levels were found to be lower in a small number of patients compared to those who were not depressed. However, it does not mention if the use of anti-depressants or anxiolytics were the cause of these lower values. This was an observation (1).
In another study, 355 patients were studied later in life, 60’s and higher in age. Lower levels were found to be lowered which could be a potential cause of later life depression. It is not clear if these patients were on anti-depressants leading to lower Vitamin D levels (2).
In one review, 4 studies were found that an improvement in the the thiamine status led to improved mood. The same study found that folate deficiency led to depression and iron deficiency anemia can lead to fatigue and depression (3).
The take home message is that it is not clear whether anti-depressants and anxiolytic agents used long-term can result in lower levels of minerals and vitamins.
However, it has been studied that lower levels of certain minerals and vitamins can lead to or be associated with depression.
Neurologybuzz.com
Reference
  1. Bender, A., Hagan, K.E., Kingston, N., The association of folate and depression: a meta-analysis. J. Psychiatric Res. 2017 Dec. 95:9-18
  2. Oude Voshaar, R.C.,Derks, W.J., Comiis, H.C., Schoevers, R.A., de Borst, M.H., Marijnissen, R.M. Antidepressants differentially related to 1,25-(OH)2 vitamin D3 and 25-(oH) vitamin D3 in laterlife depression. Transl Psychiatry. 2014, Apr. 15;4:e383
  3. Benton, D., Donohue, R.T. The effects of nutrients on mood. Public Health Nutr. 1999 Sep; 2(3A):403-409
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cannabinoids, Uncategorized

What are the risks of vaping medical cannabinoids in the state of Florida?

Virginia Thornley, M.D.
October 9, 2019
Given the recent rash of deaths thought to be caused by vaping e-cigarettes, patients are scrambling to ask their doctors regarding the risks of vaping medical cannabinoids.
Many of the reports reporting deaths have been with e-cigarettes which do have chemicals that can potentially cause irreversible damage to the lungs.  Some reports report that THC oils were used but do not state the source. THC oils were reported to be placed in the vaporizer device used for e-cigarettes to be vaped. In Florida, medical products used in vaping for medical purposes from regulated dispensaries are from all natural products, a very different set-up compared to the components found in e-cigarettes.
It is not clear if some of these reports are from tightly regulated medical marijuana dispensaries. In the state of Florida, there have been no reports of deaths related to vaping cannabinoids used for medical use that come from stringently regulated dispensaries. In the state of Florida, medical cannabinoids have strict regulations and there is a vertical distribution meaning the products are with the company from time they are grown as a seedling to the time of dispensing so that the company is in complete control of the product being dispensed.
At this point, October 2019, there have been no reported deaths due to vaping medical cannabinoids in Florida when taken from legal regulated dispensaries. The lung-related illnesses associated with vaping in Florida are related to vaping from e-cigarettes which may also have other substances added.  This is completely different from vaping the cannabinoid medical products which are all natural products from medical dispensaries.
We turn to research for the analysis of the potential risks involved with vaping. There is one study but it involves vaping cannabinoids using e-cigarette devices. The gas-thermal degraded products have not yet been thoroughly analyzed. In this study, there is potential exposure to benzene, methacrolein and methyl vinyl ketone. Tetrahydrocannabinol alone and mixed with terpenes can lead to elevated levels of isoprene. Terpenes may lead to higher gas products. Overall, gas-phase products are much lower compared to smoking products (1). There has been little research on vaping medical cannabinoids dispensed from the dispensaries and so far, no deaths have been reported from cannabinoids coming from regulated dispensaries in Florida.
This is information only not advice. Please consult with your physician.
Neurologybuzz.com
Reference
  1. Meehan-Atrash, J., Luo. W., McWhirter, K.J., Strongin, R.M. Aerosol gas-phase components from cannabis e-cigarettes and dabbing: mechanistic insight and quantitative risk analysis. ACS Omega. 2019, Sep. 16,;4(14):6111-16120
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migraine

Effects of barometric pressure changes in weather change in patients with migraine

Virginia Thornley, M.D.
October 9, 2019
A common question that is asked in the office setting is whether weather changes can increase migraines.
In one study of 98 patients followed 45 days, higher humidity between the warm months of April and September correlated with increase number of migraines (1).
In a 7-year study of ER patients, an increase of barometric pressure resulted in more ER visits by patients with migraine. There were less visits when it was a decrease in pressure. There was no correlation with migraine with the actual magnitude of barometric pressure change. Tropical air masses correlated with more ER visits compared to polar masses (2).
In a smaller study of 28 patients followed over 1 year, weather changes correlated with increased migraine frequency in 64%. 14 of those reported low barometric pressure to be associated with it (3).
In summary, despite some mixed results regarding reduction of barometric pressure, if a weather change affects a patient’s underlying condition, it is likely a trigger.
This is information only not advice please see your doctor.
Neurologybuzz.com
Reference
  1. Li, W., Bertisch, S.M., Motofsky, E., Buettner, C., Mittleman, M.A., Weather, ambient air pollution, and risk of migraine headache onset among patients with migraine. Environ. Int. 2019, 132:105100
  2. Elcik, C., Fuhrmann, C.M., Mercer, A.E., Davis, R.E., Relationship between air mass type and emergency department visits for migraine headaches across Triangle region of North Carolina. Int. J. Biometeor. 2017, Dec. 61(12):2245-2254
  3. Kimoto, K., Alba, S., Takashima, R., Suzuki, K., Takekawa, H., Watanabe, Y., Tatsumoto, M., Hirata, K., Influence of barometric pressure in patients with migraine headache. Intern Med. 2011. 50(18):1923-8
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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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