Sunday, January 22, 2017

Review: "First Steps" by Jason DaSilva


Overview

"First Steps" is a short documentary created by Jason DaSilva in 2008 that documents his response to being diagnosed with multiple sclerosis and various ways that he has tried to cope with the disease. DaSilva was diagnosed with MS at the age of 26 when his career as a filmmaker was just beginning. "First Steps" depicts DaSilva's neurological symptoms: loss of balance, inability to walk, and blurred vision. His multiple sclerosis is a form called primary progressive MS which has no cure and no treatment. DaSilva struggles with continuing his love of filmaking due to the disease, claiming, "what kind of filmmaker can't see or walk properly". 

DaSilva explains that he must use a cane to walk. In an effort to gain back his mobility, DaSilva visits a motion capture studio to determine which muscles he must strengthen in order to walk. He visits the gym regularly to strengthen his legs to avoid a complete disability. He also considers leg braces to stabilize his feet and hips, but they do little to help. DaSilva then goes to a hospital to work with experts who aid individuals with cerebral palsy. Of course, none of these methods can fully cure his condition.

Jason DaSilva, director and screenwriter of "First Steps".
To cope with the struggles of MS, DaSilva visits his mother who insists that he should consider those who are even less fortunate than himself. She gives an example of people living in shacks in Jakarta while DaSilva lives in a nice city. DaSilva thinks, "I'd be happy anywhere in Jakarta if I could walk". 

DaSilva then visits an MS support group and feels out of place with all of the older, Caucasian attendees; Jason is of Goan descent and in his mid twenties. 

The film closes with DaSilva attending a film festival in Dallas where he laments the fact that many films don't have disabled actors, simply actors portraying disabilities. There he meets actor Kumar Pallana who, at 90 years old, claims that DaSilva's disability is all in his head and with the proper exercises he can walk again. DaSilva tries the exercises, but his symptoms do not disappear. 

Despite all his failed attempts to walk again DaSilva seems to have accepted MS and determinedly he claims, "whatever happens to me, I'm gonna keep making films".

My Thoughts

DaSilva's film, though short, gives valuable insight to the feelings of anxiousness or despair that MS sufferers might feel when they are first diagnosed. Onset of multiple sclerosis often occurs during young adulthood when someone still has a large portion of their life ahead of them. Their aspirations and visions for the future can seem lost, but DaSilva insists that multiple sclerosis does not have to be the end of his dreams. 

DaSilva is young and full of life and determination. It is shocking to see someone like him using a cane. He even worries about leg braces ruining his fashion as any young person would. I think that many people assume that debilitating diseases are reserved for the elderly, but seeing how MS can affect a man in his 20's makes MS so much more devastating. 

DaSilva focuses on unconventional treatments for multiple sclerosis since his form of the disease, PPMS has no medical cure. I would be curious to also see his interactions with physicians rather than just an orthotist and a physical therapist. 

Overall the film offers an interesting inside perspective of multiple sclerosis that benefits from having the filmmaker as the patient. The documentary focuses on what someone with MS would want outside people to know rather than what a film crew thinks would make an interesting documentary.


References:

DaSilva, J. (Director & Producer). (2008). First Steps [Documentary]. 




Image Sources (in order of appearance):

"First Steps" by Jason DaSilva

http://www.newmobility.com/wp-content/uploads/2015/01/headshot.jpg


Review: "Sex and Gender Issues in Multiple Sclerosis" (Harbo et al.)

This is a review of the article "Sex and Gender Issues in Multiple Sclerosis" which can be read here.

Article Summary

In recent decades the ratio of women to men that contract multiple sclerosis has increase from 2.3:1 to 3.5:1. The prevalence of autoimmune disorders like MS has been increasing in women significantly more than it has in men. This article investigates some of the effects of sex on multiple sclerosis symptoms and treatment effectiveness in an effort to begin to understand why so women are more likely to have the disease.

Certain genetic markers have be shown to correspond to higher risk for multiple sclerosis, including the HLA marker discussed in the previous post. After reviewing various GWAS (genome wide association studies) the researchers of this article claim that there is no real variation between men and women with regard to these genetic markers. As the article claims though, "our methods are constantly improving" differences in genetic expression of MS between men and women could be identified in the future. 

The scientists also analyzed regions of DNA other than the HLA loci that are tied to sex differences. They hypothesized that how men and women react to sun exposure and vitamin D intake could be different and cause different levels of risk for the disease. Other scientists have theorized that the X chromosome is related to immune function. Women, with incorrect X chromosome inactivation, may get incorrect doses of immune genes which could explain a higher prevalence of autoimmune diseases in women. 


A woman has two chromosomes in each cell. Usually one X chromosome
is inactivated to ensure that she receives the correct dosage of each gene

Sex hormones have also been analyzed as a potential culprit for the differences in men and women. Pregnant women, with high levels of the hormone oestriol, have fewer relapses of neurological symptoms. Not much is known for certain about the effect of sex hormones, but the scientists mention a trial taking place at the time of the article's publication (2013) that is studying the use of oestriol as a treatment for MS. 
Women are much more likely
to develop autoimmune diseases
though scientists don't always know
why.

In studying EAE (experimental autoimmune encephalomyelitis or, animals with and induced MS-like disease), scientists have found that testosterone may serve as a mild protection against autoimmune disease. Furthermore, these studies have indicated a difference in how vitamin D alleviates MS symptoms in male and female mice with female mice responding to vitamin D treatment more. 

Multiple sclerosis experts have had varying views on pregnancy. While it was once thought to be dangerous for women with the disease, scientists have found that MS relapses decrease during pregnancy. This is thought to be because a woman's immune system is suppressed so as not to attack the fetus. As suppressed immune system would lead to fewer symptoms of an autoimmune disorder. It should be noted that after pregnancy, relapse can still and often does occur.

There are multiple other suspected relationships between MS and pregnancy and breastfeeding but the current research is too sparse for any real conclusions to be made. The authors suggest that further studies must be done to better understand autoimmune disparity between the sexes. 

My Thoughts

The article did an excellent job of providing future questions for research and indicating what gaps in our knowledge of MS we need to fill. I agree that more large studies must be conducted to better understand the higher prevalence of the disease in women. I would further be interested to research more about how the X chromosome could be related to autoimmune diseases. Perhaps this course of action would not only explain the growing ratio of women to men, but also provide a better understanding of how to treat and/or cure autoimmune disorders.




References:


Harbo, H. F., Gold, R., & Tintoré, M. (2013). Sex and gender issues in multiple sclerosis. Therapeutic Advances in Neurological Disorders6(4), 237–248. http://doi.org/10.1177/1756285613488434


Image Sources (in order of appearance):

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http://www.clipartkid.com/images/563/light-pink-female-symbol-clip-art-at-clker-com-vector-clip-art-KxPUzf-clipart.png



Transmission and Treatment of Multiple Sclerosis

Who is at risk?

While the cause of multiple sclerosis is still unknown, there are certain populations known to be at higher risk for the disease. As mentioned in the previous post, these factors include: genetics, environment, and exposure to certain pathogens (Loma, 2011).

Diagram of human chromosome 6, detailing the HLA locus.
The genetic component of multiple sclerosis can be observed in instances of higher frequency of the disease among related individuals. If someone has a first degree relative with multiple sclerosis, their chance of contracting the disease increases "40-fold" (Loma, 2011). Multiple loci in various chromosomes are suspected to contribute to the genetic basis of the disease. However, the HLA locus on chromosome 6 is the current front-runner thought to cause the most susceptibility (Loma, 2011).

The second component, environment, can be seen by analyzing prevalence of the disease in different global regions. Higher latitudes (both north and south of the equator) are associated with higher prevalence of multiple sclerosis (Alharbi, 2015). Even when adjusted for genetic similarities within geographical regions, latitude still has a significant affect on risk (Simpson, 2011). Newer studies suggest that this environmental risk factor is tied to vitamin D intake during adolescence. Individuals in higher latitudes have greater instances of vitamin D deficiency because of less sun exposure (Alharbi, 2015). While the protective effects of vitamin D are not fully understood, it is clear that vitamin D exposure (through sunlight or oral supplements) correlates to lower risk for the disease. 

Sufficient levels of vitamin D in the blood lower risk for MS.

The final risk factor speculated to be associated with multiple sclerosis is exposure to certain pathogens. In cases of  Relapsing-Remitting Multiple Sclerosis, certain viral infections are known to cause relapses (Loma, 2011). If viruses can trigger a relapse, perhaps they are also responsible for onset of the disease. Herpes virus type 6, Epstein Barr virus, and the bacteria mycoplasma pneumoniae are all being researched for a possible link to MS (Loma, 2011). There is significant evidence that individuals with multiple sclerosis have higher numbers of Epstein Barr virus antibodies in their blood and cerebrospinal fluid (Pender, 2014). 

Viral infections alone are not likely the cause of multiple sclerosis. However, the combination of certain viral exposure with genetic predisposition and vitamin D deficiency likely put an individual at much greater risk for the disease. 


Transmission

Multiple sclerosis is not contagious horizontally between hosts (NMSS - FAQ). Because there seems to be a genetic component tied to the disease, one could say that it is transmissible vertically between parents and their offspring. However, just because an individual has the genetic markers at the HLA locus, does not mean that they will necessarily develop the disease.


Treatment/Prevention

Unfortunately, there is no known cure for multiple sclerosis (Loma, 2011). Patients diagnosed with the disease receive treatment to manage their symptoms and relapse periods. According to the National Multiple Sclerosis Society, treatment falls under five categories:

1. Modifying the disease course with drugs that lessen the frequency of relapses. These medicines can be injected intravenously like Avonex, or taken orally like Gilenya (NMSS - Treating MS). 

2. Treating exacerbations or inflammation in the nervous system with corticosteroids like prednisone. Not all exacerbations need to be treated medically. However, severe inflammation can often cause debilitating symptoms that interfere with daily life and treatment is needed (NMSS - Treating MS).

3. Managing symptoms of multiple sclerosis like fatigue, walking difficulties, and bladder problems. Because these symptoms are not specific to MS, they can be treated with other methods (NMSS - Treating MS).

4. Rehabilitation programs that help improve an individual's everyday functioning. These programs can focus on cognitive rehabilitation or physical/occupational therapy depending on the loss of function (NMSS - Treating MS).

5. Emotional and mental health support is crucial for chronic, incurable diseases like multiple sclerosis. Multiple sclerosis, being a disease that affects the nervous system, can cause depression, anxiety, and mood swings that should be treated by physician or counselor (NMSS - Treating MS).


Eight of the more than 12 FDA approved drug treatments for MS.

As the causes of multiple sclerosis become better understood, prevention methods can be implemented. Based on current science, researchers suggest that vitamin D intake during childhood and adolescence can significantly decrease the risk for MS (Dudani, 2011). Taking vitamin D supplements is a safe preventative measure that avoids the carcinogenic risks of sun exposure. 


References:


Alharbi, F. M., (2015). Update in vitamin D and multiple sclerosis. Neurosciences, 20(4), 329-335. http://doi.org/10.17712/nsj.2015.4.20150357

Dudani, S. J., Kalhan, S., & Sharma, S. P. (2011). Vitamin D and multiple sclerosis: Potential pathophysiological role and clinical implications. International Journal of Applied and Basic Medical Research1(2), 71–74. http://doi.org/10.4103/2229-516X.91146

Loma, I., & Hayman, R. (2011). Multiple Sclerosis: Pathogenesis and Treatment. Current Neuropharmacology, 9(3), 409-416. http://doi.org/10.2174/157015911796557911

Multiple Sclerosis FAQs. (2017). National Multiple Sclerosis Society. Retrieved from: http://www.nationalmssociety.org/What-is-MS/MS-FAQ-s

Pender, M. P. & Burrows, S. R. (2014). Epstein-Barr virus and multiple sclerosis: potential opportunities for immunotherapy. Clinical & Translational Immunology. http://doi.org/0.1038/cti.2014.25

Simpson, S., Blizzard, L., Otahal, P., Van der Mei, I., & Taylor, B. (2011). Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. Journal of Neurology, Neurosurgery, and Psychiatry. 82(10), 1132-1142. http://doi.org/10.1136/jnnp.2011.240432

Treating Multiple Sclerosis. (2017). National Multiple Sclerosis Society. Retrieved from: http://www.nationalmssociety.org/Treating-MS/Comprehensive-Care



Image Sources (in order of appearance):

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https://www.dermaharmony.com/images/articles/vitamind550.jpg

https://www.uspharmacist.com/CMSImagesContent/2012/1/USP1201-MS-T1.gif



Sunday, January 15, 2017

History, Etiology, and Symptoms of Multiple Sclerosis


What is Multiple Sclerosis?


Multiple sclerosis is a chronic autoimmune disorder where an individual's immune system attacks and damages the protective covering of nerve cells (PubMed Health). This covering, called myelin, is crucial for proper nervous system function as it insulates the electric current that neurons use to communicate.

A neuron with a protective myelin sheath around its axon.
                                 
Currently, four different "types" of multiple sclerosis are recognized:

Clinically Isolated Syndrome (CIS): CIS is a 24-hour episode of MS-like symptoms caused by inflammation and demyelination of nerve cells. It can be a one time occurrence or can lead to progression of true multiple sclerosis(NMSS-Types of MS).

Relapsing-Remitting MS (RRMS): The most common form of MS, RRMS, follows a pattern of worsening symptoms (relapse) followed by periods of near complete recovery (remission)(NMSS-Types of MS)

Secondary Progressive MS (SPMS): Many of the individuals diagnosed with RRMS will progress to SPMS. SPMS is a form of MS characterized by worsening of neurologic function(NMSS-Types of MS).

Primary Progressive MS (PPMS): PPMS is a form of MS where symptoms and neurologic function continue to worsen from onset of the disease without any periods of remission(NMSS-Types of MS)

Multiple sclerosis statistics


Multiple sclerosis is a relatively uncommon disease, affecting only around 400,000 people in the US (Loma, 2011) and 2.3-2.5 million people worldwide (NMSS-Who Gets MS). The disease has noticeable geographic and ethnic influence and is more likely to occur in Caucasians and/or in populations that are far from the equator. Geography and ethnicity seem linked as some non-Caucasian populations that are far removed from the equator, such as the Inuit, show low incidence rates of the disease (NMSS-Who Gets MS). Multiple sclerosis also affects certain genders and age groups differently, as women and young adults (20-40 yrs) are more susceptible to the disease (Loma, 2011). In the past decade, some research has indicated that the geographical influence in incidences is decreasing and the ratio of women to men is increasing (Alonso, 2008).



A Brief History


Evidence of multiple sclerosis has existed since the mid 1800's in the form of autopsy reports (Roth, 2005). In 1868, professor Jean-Martin Charcot associated neurological symptoms of living patients with the characteristics of the disease found in autopsies. He described and named the disease, but was unable to determine its cause or an effective treatment (Rolak, 2003). 
In the early 1900's, Dr. Thomas Rivers conducted research that proved that MS was not a viral disease. Some scientists thought that MS could be related to the immune system, but this theory wasn't studied further until the 1960's (Roth, 2005).
In the late 1900's, MRI and new drug treatments enabled doctors to better detect and treat MS (Roth, 2005).

The mystery of the cause of MS persists, but continuing research is uncovering more about the disease in the hope to find a cure. 


Etiology

Currently, there is no definitive cause of multiple sclerosis, however epidemiologists suspect a cocktail of genetic, environmental, and viral etiological agents are responsible for the disease. Individuals with first degree relatives who have contracted the disease are much more susceptible than those with no family history (Loma, 2011). This pattern of incidence would indicate a genetic component of the disease. Environmental factors also seem to play an important role due to trends of higher prevalence in regions further from the equator. Researchers have noted that individuals migrating from a region with high MS incidence rates to a region with low incidence rates are less likely to obtain the disease (Loma, 2011). Finally, some scientists have focused their attention on certain pathogens that could increase an individual’s risk to contract multiple sclerosis (Loma, 2011). These three etiological components will be discussed in further detail in the second blog post.


Symptoms


Because the nervous system is so crucial to so many body processes, multiple sclerosis can present in a wide variety of symptoms. Some symptoms affect the eyes, like blurred vision, red-green color distortion, and temporary blindness (PubMed Health). Other signs can be mental, like depression, dizziness and vertigo, mood swings, and cognitive problems (NMSS-MS Symptoms). Another set of symptoms can be physical, including bladder dysfunction, muscle weakness, numbness, fatigue, and difficulty with coordination and balance (NMSS-MS Symptoms). Symptoms of multiple sclerosis can range in severity from being a mild annoyance to a life-altering disability. 


Diagnosis


The symptoms of multiple sclerosis can be confounding at times due to the fact that they are not specific to this one disease. Other, differently treated illnesses, can present clinical signs that are similar to MS (PubMed Health). In order to diagnose the disease properly, doctors will utilize a patient's medical history with a range of neurological tests. These tests include MRI's to search for inflammation in the nervous system, evoked potential tests that measure nervous system response time, and spinal taps to eliminate other possible diseases (PubMed Health). 



References:


Alonso, A. & Hernán, M. A. (2008). Temporal trends in the incidence of multiple sclerosis: A systematic review. Neurology 71(2), 129-135. http://doi.org/10.1212/01.wnl.0000316802.35974.34

Loma, I. & Heyman, R. (2011). Multiple Sclerosis: Pathogenesis and Treatment. Current      
Neuropharmacology, 9
(3), 409-416. http://doi.org/10.2174/157015911796557911


MS Symptoms. (n.d.). National Multiple Sclerosis Society. Retrieved from: http://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms

Multiple Sclerosis. (n.d.). PubMed Health Glossary. Retrieved
from: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024311/


Rolak, L. A. (2003). MS: The Basic Facts. Clinical Medicine and Research 1(1), 61-62.         Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1069024/

Roth, E. (2005). The History of Multiple Sclerosis: How Far Have We Come? Healthline
Media.
Retrieved from: http://www.healthline.com/health/multiple-sclerosis/history#Overview1


Types of MS. (n.d.). National Multiple Sclerosis Society. Retrieved from: http://www.nationalmssociety.org/What-is-MS/Types-of-MS

Who Gets MS? (n.d.). National Multiple Sclerosis Society. Retrieved from: http://www.nationalmssociety.org/What-is-MS/Who-Gets-MS



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