Posts about neurology from 2 of our recent medical students

drexel_medicine_white_coat_2012

 

Posted by Ilya Grinberg:

Last week I participated in the MDA clinic and there was one patient who really stuck out in my mind. He was a 17 year old male who had Duchenne Muscular Dystrophy. He was completely wheelchair-bound and could barely move any of his extremities. This obviously meant that he was completely reliant on people to take care of him and that he could not participate in the day to day activities that a normal person could. He was also starting to have breathing difficulty and probably would need to start therapy on a ventilator soon too.

DMD is an x-linked recessive disorder that affects boys from an early age. It affects 1 out of 3600 boys so it is not too uncommon. The disease is due to a mutation of the structural protein Dystrophin which is normally found in all muscles. The protein is found on the X chromosome which explains why it is an X-linked disease. Patients are usually born normally but will start gradually developing symptoms during the first few years of life. The first observations are usually progressive muscle weakness in proximal muscles in addition to muscle atrophy. One of the key clinical signs in DMD is calf psuedohypertrophy which occurs due to fibrosis of the necrotic muscle tissue. Another common finding that presents early on is Gower’s sign, where the patient uses his arms to stand up due to weakness in the proximal leg muscles.

Click here to find out more about DMD.

 

Posted by John Soliman:

What is Neurology one may ask? Prior to and during medical school I feel like the exposure to the study of neurology was very limited. Interaction between neurological patients and medical professions was far and few between. I have had little encounters with the realm that lies ahead. Prior to starting the clerkship I was very intimidated due to my lack of knowledge and ignorance. I can say jokingly I barely knew how to spell Neurology. Even the basics of neurology such as anatomy was daunting usually getting hung up on learning one part or area as seen in this video. I have to say I had something in common with Pinky.

After the 4 weeks of neurology I have realized that neurology covers a broad realm of knowledge and information on the central and peripheral nervous system.

During my clerkship I was lucky enough to be exposed to many patients encountering a lot of this medical conditions and problems. I was able to identify and correlate symptoms with disease states and vice versa.

The most memorable experience was the MDA clinic. I was able to meet and was integrated into the care of a lot of the Myotonic dystrophy patients. I was able to see hear their day to day life experience, talk to their care givers and be able to help with their care. After seeing patients like this it really brought “problems” Into perspective. The amazing thing was the broad range of how these medical conditions affect each individual differently.

I had the opportunity to see two brothers who are both affected with Myotonic Dystrophy. One brother can walk, talk and act normal with minimal weakness while the other was wheel chair bound. Talking to them brought home how a muscular dystrophy can affect the lives of affected individuals. Myotonic dystrophy is an autosomal dominant genetic process which means it can affect 50% of the carriers offspring. This may affect a family’s decision on having kids both mentally and psychologically. In this specific case, one of the brothers and his wife decided to adopt children due to the high risk of having a child with myotonic dystrophy. Dealing with something like this is a full time job on its own so it can be draining mentally, physically and financially on families.

Overall the experience has been great as I have gotten to see patients with medical conditions that I may not be able to see again. This clerkship has been knowledgeable and I has encountered a broad real of neurology that I never had experienced in the past.

Click here to find out more about Myotonic Dystrophy.

Click here to find out more about MDA Clinic at Monmouth.

Advertisements

Recent study links marijuana use to structural brain changes

 

 

Post  prepared by Amanda Baker, Drexel University College of Medicine Class of 2014

christie1

 

A study recently published in the Journal of Neuroscience by Harvard researchers have linked casual marijuana use to structural changes in distinct areas of the brain.

These areas, the nucleus accumbens and amygdala, and are largely involved in recognition of reward, motivation, fear, and memory.  In this study, the brain scans of 20 young adult casual marijuana users were compared to those of 20 young adult non-users.

While the results clearly demonstrated significant structural differences between the two groups, the structural changes have not been correlated with consequences in mental or physical functioning.  In other words, researchers aren’t entirely sure of the impact of these brain changes.

 

Casual marijuana use may damage your brain

The debate regarding the use of marijuana medically and recreationally is ongoing in the United States.

Although the Drug Enforcement Administration(DEA) categorizes this drug as Schedule I, “with currently no accepted medical use and a high potential for abuse”, many argue that there is, in fact, much benefit to medical marijuana, especially in comparison to other sedating pain medications.

This is reflected in 21 state laws which have legalized medical marijuana to varying degrees.

Last summer, Dr. Sanjay Gupta completed a documentary “Weed” highlighting the benefit of medical marijuana:

However, some states such as Washington and Colorado, have gone one step further by legalizing marijuana for both recreational and medical use.

Given the ongoing research on the effects of marijuana, perhaps this new study will call into question continued legalization of the most widely used recreational drug in America.

 

Click here to find out more.

 

Helmets: do they work to prevent concussions?

Posted by Vanessa Fabrizio, MSIV Drexel University College of Medicine

FOOTBALL: the most popular sport in America. Little boys dream of growing up and playing in high school, then college, then hopefully the NFL. Even little girls dream of dating football players in school or marrying a NFL superstar.

katherine-webb-aj-mccarron

Those who have never played football can pour money into the sport by simply watching it on TV or more drastically via sports betting. With advancements in the sport and the increasing athelticism of the players, the injury risk has drastically increased while the lifetime of a player in the NFL has decreased. More attention is being brought to the media about concussion and their long term sequelae in professional athletes, yet not enough people question how well the helmets are actually working.

What is a concussion?

concussion

Concussion: a mild traumatic brain injury that leads to a temporary loss of brain function.  Symptoms of a concussion are commonly headaches, dizziness, nausea, vomiting, difficultly on ones feet and balancing, and loss of fine motor coordination. Other symptoms can include light sensitivity, blurry vision, tinnitus, and can even produce seizures. Most individuals who experience a concussion will also experience post-traumatic amnesia and experience difficulty paying attention and disorientation. Post concussive syndrome exists and these symptoms can linger for months affecting lifestyle in many ways.

Treatment for concussion is typically and simply rest. Avoiding head trauma is key to recovery.

Football is not the only sport where its players experience concussions. Boxing is an extremely dangerous sport and many of its victims experience neurological deficits due to their involvement. Soccer, basketball, volleyball, softball, and baseball to name a few all have increased risks of concussions greater than the general public.


This video demonstrates that not only professional players are at risk as it shows a 12yr old on the wrong end of a “hard hit”.

What do the studies say about helmet protection?

helmet

Recently an article in the LA times was published that talked about how the American Academy of Neurology is currently studying the effectiveness of different football helmets on the market today and how well they decrease concussion rates. The research that will be presented is showing that no helmet on the market today is actual effective in preventing concussions. However, it appears that the helmet this study rated as number 1, was rated last in a study at Virginia-Tech Wake Forest University School of Biomedical Engineering and Sciences. Obviously this shows that our testing of how effective helmets work isn’t standardized yet or up to par. As mentioned above, the sport of football itself has advanced so now helmets need to advance and the testing of the efficacy of these new helmets need to advance as well.

Should we encourage children to stop playing football to prevent them harm? As an avid football lover myself, I think that this is not the solution. We need to continue to raise media attention in order to expedite the process of creating these newer, safer helmets. Education about concussions need to be taught to young athletes as well as appropriate tackling measures to ensure safety. The NFL association has been good about updating the rules and regulations of the game to ensure player safety with fines and penalties for unnecessary roughness and hits. Lets hope they continue this way and it continues to trickle down all the way to the peewee leagues.

CLick here to link to the LA times article.

STIFF PERSON SYNDROME: A misleadingly flippant name for a serious disease

SPS1

Posted by Jennifer Ding, MSIV Drexel University College of Medicine

What is Stiff Person Syndrome (SPS)?

exaggerated lumbar spine

Exaggerated lumbar lordosis in SPS

Stiff Person Syndrome (yes, the official moniker) is a very rare autoimmune disease of the nervous system that affects maybe 1 in 1,000,000 people worldwide. Most patients experience fluctuating, involuntary muscle rigidity in the trunk and limbs, an exaggerated lumbar curve, and a heightened sensitivity to their environment.

Loud or unexpected noise, touch and emotional distress can actually set off muscle spasms or even falls in those afflicted.

Attacks of spasms are usually unpredictable, last for minutes and tend to recur over hours. These spasms can be so intense that they actually can cause.

The rigidity seen in SPS is characterized by a stiffness (hence the name) that begins over several months along the spine and spreads to the legs. In the lucky few, the fluctuating rigidity becomes fixed leading to difficulty walking, bending, and frequent falling.

Who gets SPS?

Moersch and Woltman first described SPS in 1956 based on 14 cases that were observed over 32 years. It was initially called “stiff man syndrome” before the disease was found in females and children as well.

Today, we see that SPS affects twice as many women as men and is frequently associated with other autoimmune diseases, such as Diabetes Mellitus Type 1, thyroiditis and vitiligo. Age of onset varies between 30 to 60 with it occurring most frequently in people in their 40s.

What causes SPS?

Now for the science behind SPS: like any autoimmune disease, the problem is thought to lie with antibodies that attack the body’s own cells or enzymes. Patients with SPS have antibodies against glutamic acid decarboxylase (GAD), an enzyme, that produces gamma-aminobutyric acid (GABA), a chief inhibitory neurotransmitter (a chemical) that plays a crucial role in regulating our central nervous systems. GABA is also directly involved in regulating muscle tone.
Mechanism

The exact details of the way GAD antibodies cause SPS remain unknown. Many people with GAD antibodies don’t develop SPS. But most patients with SPS have a high level of GAD antibodies in their blood as well as antibodies that inhibit GABA-receptor-associated-protein (GABARAP). Therefore, scientists hypothesize that the root cause of the muscle rigidity and spasms seen in SPS lie in a GABA impairment.

Think of it this way: muscles work in pairs. When one contracts, the other relaxes, and vice versa. GABA is key in regulating this relaxation and without it, both muscles end up contracting. When both muscles contract, they lose the ability to work together, leading to a stalemate, or stiffness that we see in patients with SPS.

How is SDS diagnosed?

The level of GAD antibodies can be measured in the blood and cerebrospinal fluid (CSF). As aforementioned, the mere presence of GAD antibodies in the blood does not directly correlate with a diagnosis of SPS. Instead, the higher the level of GAD antibodies in the blood, the more likely SPS is the diagnosis.

Electromyography (EMG) can also be used to demonstrate involuntary neuronal firing in muscles.

How is SPS treated?

While there is no cure for SPS to date, there are treatment options that are aimed at symptom relief. Benzodiazepines, such as Valium (diazapam) or Ativan (lorazepam), that act similarly to GABA are the primary treatment for symptom relief. These drugs have muscle relaxant and anticonvulsant effects. Baclofen, another type of GABA-agonist that is dispensed from an implanted pump, can be used as a muscle relaxant. Neurontin (gabapentin) is a seizure medication that has also been used for symptom relief. However, SPS tends to worsen over time, leading to patients requiring increased dosages of drugs.

Intravenous immunoglobulin (IVIG) that target the antibodies themselves are also used in patients with advanced disease. IVIG has been shown to decrease stiffness and the heightened startle reflex. Steroids, rituximab, and plasma exchange have also been used to target the immune system in SPS patients, but the benefit of these treatments remains unclear.

Additional reading material

Click here for more information on SPS, the most up-to-date research on the neurological disease, and social networking for those interested, afflicted, or who have family members who are afflicted.

Click here for an article about a patient with SPS.


News segment about a young dancer with SPS.

Plasma Exchange For Myasthenia Gravis

Posted by Christopher Orr,  Drexel University College of Medicine 2014

Ms. AB presented last week in the Neurology office with shortness of breath and weakness, and she knew it was from her myasthenia gravis.

She was already on an anticholinesterase inhibitor, but it was very apparent that she was suffering from a severe exacerbation of myasthenia gravis.

We sent her to the Emergency Room in order to be admitted so she could receive plasmapheresis in order to minimize the antibodies that were blocking the acetylcholine receptors at her neuromuscular junctions.

To give a brief history of Ms. AB’s myasthenia gravis, she was diagnosed in the Fall of 2013 when she presented with muscle weakness and difficulty breathing.  She was treated with plasmapheresis during that initial episode, and improved.

In the interim, she had also been given steroids to reduce the immune response of her autoantibodies towards her acetylcholine receptors, but this actually caused increased leg weakness, more likely from steroid myopathy than myasthenia gravis.

Unfortunately she experienced another exacerbation in December, and she was treated with intravenous immunoglobulin (IVIG).  What is interesting is that when she was treated with IVIG, her symptoms did not improve as they had done plasmapheresis.

There is limited research on the efficacy of IVIG in comparison to plasmapheresis in the literature.  A comparison study of IVIG vs. plasmapheresis waspublished by Mandaway et. al. in the Annals of Neurology in 2010 and included 1,606 patients – both therapies showed similar clinical outcomes in terms of both mortality and complications.  From a purely financial perspective, IVIG was more cost effective because of lowered length of stay and total inpatient charges.

However, a smaller study published by Stricker et. al. in JAMA in 1993 reported 4 patients who did not respond to initial IVIG treatment but later responded to plasmapheresis.  There were no definite prognostic factors mentioned that might explain why plasma exchange may be better than IVIG in certain patients.  The article stated further research was needed.

Ms. AB did present with myasthenia gravis at a later age of onset than is typically observed.  For future studies that compare IVIG to plasmapheresis, I would be highly interested in a subgroup analysis on a patient’s age and the efficacy of the 2 treatment modalities of IVIG and plasmapheresis.

When we saw Ms. AB in the hospital, she was already doing much better with plasmapheresis.  In addition, we were For the future, Ms. AB would likely be discharged to a rehabilitation facility and there are considerations to start her on CellCept (mycophenolate mofetil).  It would be preferential to start the patient on CellCept as an immunomodulatory drug to decrease the autoantibodies against her acetylcholine receptors and reduce her need for plasmapheresis.

I chose to write a reflection on Ms. AB for 2 reasons.  First, she and her husband are both very kind people, and it is a pleasure to see her improve.  Second, I love technology in medicine and healthcare.  When we saw Ms. AB’s plasmapheresis treatment, it was fascinating to see the apparatus that was using centrifugal force to spin her blood and separate her plasma from the WBCs, RBCs, and platelets.  The mechanism behind performing the plasmapheresis was to take off her plasma, which had the autoantibodies, and replace new plasma with albumin.  Please look below to see a picture of a plasmaphresis apparatus and an explanation of how it works.  After my experience seeing Ms. AB, it was a pleasure to treat her and learn from her condition.

OLYMPUS DIGITAL CAMERA

Pictured above is an apparatus that is used for the plasmapheresis treatments.  Although this machine may seem very intimidating, it operates on the basis of how spinning blood can separate the blood into different components, such as the plasma, RBCs, WBCs, and platelets. To explain in a simple manner, a central venous line is obtained from the patient so blood can be brought to the machine and spun.  After the plasma is removed by the centrifugal force, the remaining components (RBCs, WBCs, and platelets) is added with albumin and saline (a protein found in plasma) then reintroduced into the patient.

In many instances, diseases can be complicated to comprehend.  I wanted to give a better understanding of myasthenia gravis.  I hope this picture and caption that I included make the disease easier to digest.

nmj achr

The above image shows the synapse of a neuromuscular junction.  In a healthy patient, the acetylcholine can bind the acetylcholine receptor and produce a response in the muscle.  In a patient with myasthenia gravis, the antibody (shown in green) is blocking the acetylcholine receptor and preventing the acetylcholine in the synapse from reaching the muscle.  This picture is a good educational tool because it also shows how the treatment of pyridostigmine (Mestinon) can improve a patient’s symptoms.  The acetylcholinesterase (AChE, the red pac-man figure) is what degrades the acetylcholine in the synapase.  Pyridostigmine is an anticholinesterase inhibitor and impedes the red pac-man figure in the picture from working.  Therefore, pyridostigmine increases the amount of acetylcholine in the synapse that can reach the receptor and will improve the symptoms in an episode of myasthenia gravis.

Duchenne Muscular Dystrophy

Posted by Elliot Dubowitch from Drexel University College of Medicine Class of 2014

Duchenne muscular dystrophy (DMD) is one of the four main groups  of muscular dystrophy, a muscle disorder that affects and weakens the musculoskeletal system.

Muscular dystrophies are genetically inherited and progressive.

DMD is inherited in an x-linked manner.  This means that the mother, who is unaffected, is a carrier for the disease and has a 50% chance of passing it on to her male children.

The disease is caused by a deficiency in the Dystrophin protein, a complex that anchors the muscle to surrounding tissue.

dystrophin

This disease has a wide spectrum of symptom severity, depending on the type of genetic mutation, with Duchenne being very severe, and Becker’s muscular dystrophy being much more mild.

The symptoms in DMD are not usually present at birth.  As the child ages, however, they symptoms will gradually become worse and worse.  Most children are unable to walk by thirteen years of age and die in their twenties due to respiratory failure.

One of the earliest signs of DMD is called to as the “Gower Maneuver.”  Although not pathognomonic for DMD, this maneuver is a sign for proximal muscle weakness and is often correlated with DMD.  Below is a clip of a child performing to Gower’s maneuver to stand.  The patient must “walk” up his body using his hands from a sitting position due to weakness in his hip and thigh muscles.  Below is a video clip demonstrating this.

Another early sign is calf pseudohypertrophy.  Although the muscle looks bigger, it is not necessarily stronger, as the functional muscle is replaced by nonfunctional fibrous tissue.

Unfortunately, there is currently no cure for DMD.  However, there is symptomatic treatment available, such as respiratory support, cardiovascular monitoring and treatment and (if needed) surgery for scoliosis.

Steroids are the only current medication that has been shown to keep the boys walking longer.  A study was conducted in which one group of boys were given steroids daily, whereas the other group of boys were given steroids 10 days on and 10 days off.  The boys receiving daily steroids walked on average until the age of 14.5 year, while the boys receiving steroids intermittently walked to only 12 years of age.  The boys receiving continuous steroids also had more side effects including weight gain, mood swings, increase risk of infection, and other side effects of steroid usage.  If one is to consider steroid use, it is imperative to remember that it must be used at the time the child is still ambulating.  The boy will not regain lost function, however he may retain his current function longer.  In the future we hope that new drugs like VBP-15 will hopefully provide the benefits of corticosteroids without some of the side effects.

Genetic research is currently being done to hopefully find a cure for this disease.

Lytico-Bodig Syndrome, You Might Get it From Eating Bats

Posted by Daniel Rubio, Drexel University College of Medicine Class of 2014

“A man” obsessing over “bats”…

“A man” eating “bats”…


The patients above are displaying symptoms resulting from a disease known as Lytico-Bodig Syndrome (LBS), a neurologic disease resembling amyotrophic lateral sclerosis (ALS/Lou Gehrig’s Disease), Parkinson’s disease, and Alzheimer’s disease.  The country with the greatest number affected is the US territory of Guam.  In fact, between the 1940-1960 it was the leading cause of death among the Chamorro people, a tribe found on the island of Guam.  The afflicted were usually between the ages of 25-40 years of age.

What’s up with the bats?

Although yet to be proven, it is believed that the high incidence of LBS is due to the consumption of fruit bat, a cultural delicacy on the island.  These fruit bats feed on specific fruits containing high concentrations of an altered amino acid called beta-N-methylamino-L-alanine (BMAA). BMAA is a known neurotoxin and is believed to be the cause of LBS.  BMAA is a protein building block that is incorporated into neuronal proteins to produce an abnormal form that creates clumps with neurons resulting in their dysfunction and death.

I don’t eat bat though?

I addition to the high concentrations found in the fruit bats on the island of Guam, multiple sources have been proposed leading to BMAA exposure within the United States.  Certain bacteria in fresh and salt waters produce BMAA; and, fish and crustaceans will concentrate BMAA within their tissues when they consume the bacteria as part of their normal diet.  It is believed that human consumption of fish and crustaceans in at-risk areas might increase the incidence of neurodegenerative diseases, like Alzheimer’s, Parkinson’s, and Lou Gehrig’s.  This association has been seen in many areas within the United States, especially around the gulf regions and around large bodies of water.  Click here for more details about this.

Am I more lytico or bodig?

Presenting symptoms exist along the continuum of lytico-bodig.  Patients on the lytico spectrum present more like ALS/Lou Gehrig’s disease.  These patients have muscle wasting/atrophy and accompanying weakness, paralysis of mouth and tongue, and an inability to swallow resulting in choking to death.  Over time, paralysis involves the breathing muscles requiring mechanical ventilation to help the patient breath and to prevent choking on secretions.  Lytico patients remain aware of their deterioration.  The form of LBS is fatal in all cases.

On the other end of the spectrum, patients with bodig presentations look more like Parkinson’s disease and Alzheimer’s disease patients.  Bodig patients present with “freezing” with progressive immobility with loss of starting purposeful movement and loss of spontaneous movement.  Progressive dementia with loss of speech and irrational behavior, including violence and rapid fluctuations in mood, are common.  Over time, patients are left in stiff and immobile postures with inability to speak and swallow.

How would I know if I had LBS?

Currently Lytico-Bodig syndrome is diagnosed based upon appropriate history and physical exam by a neurologist.  Definite LBS is declared in post-mortem autopsy.  However, there is research being done to develop rapid tests using cerebral spinal fluid analysis.

What can I do if I have LBS?

Treatment is mainly supportive as is based upon symptoms present, whether it’s Parkinson’s, Alzheimer’s, ALS, or a combination of the three spectrums of diseases.   The more the symptoms resemble Lytico, the greater the mortality: in patients with predominantly lytico-type symptoms the disease is practically 100% fatal.