Tonight’s webinar with UCLA neurologist Dr. Susan Perlman was terrific!
Lily, in our local support group, said that Dr. Perlman provided the first diagnosis of MSA to Lily’s mother.
Dr. Perlman’s powers of explanation are impressive. She seems very interested in educating patients. She thinks patients must be aggressive about getting education and information from their MDs. She had interesting things to say about stem cell therapy in China. My notes from the webinar are below. If you attended, please add to or correct anything I’ve said below.
Robin’s Notes from
Susan Perlman, MD, UCLA Ataxia Clinic Director
Topic: Ataxia, OPCA, and MSA-C
September 17, 2009
Ataxia is a lack of coordination of muscle movements
It is caused by problems in the brain or nerves
Problems in the balance center of the brain (cerebellum) –> “cerebellar ataxia”
Other types: sensory ataxia, vestibular ataxia
The causes are different of the different types of ataxia
Tonight we are talking about cerebellar ataxia
Image of the brain found here:
It’s important to know the brain areas and be able to speak with your MD about them.
Types of cerebellar ataxia include:
* Pure cerebellar ataxia
* Cerebellar ataxia with problems in the brainstem = OPCA (olivo ponto cerebellar atrophy)
* Cerebellar ataxia with problems in the spinal cord = spinocerebellar ataxia
* Cerebellar ataxia with problems that look like Parkinson’s = MSA or PSP (also called Parkinson’s Plus syndromes)
* Cerebellar ataxia with problems that look like Parkinson’s and have memory problems = PSP
A neurological exam will tell you what type you have. This is important because the causes are different, and the treatment may be different. Some causes are genetic (inherited), some are not.
MDs usually refer to cerebellar ataxia and OPCA as the same thing.
Two types of MSA: MSA-C (cerebellar) and MSA-P (parkinsonism)
PSP and CBD have problems of dementia (memory and thinking).
National Ataxia Foundation – ataxia.org
Friedreich’s Ataxia Research Alliance – curefa.org
Cooperative Ataxia Group – cooperative-ataxia-group.org
WeMove – wemove.org
CurePSP – curepsp.org
The UCLA Ataxia Clinic has seen 1565 patients in the past 10 years. The clinic evaluates about 150 new patients each year. 40% of cases have either FA or a known genetic (inherited) ataxia. So 60% of cases have an unknown gene or non-genetic cause. (24% have pure cerebellar ataxia. The next largest group is OPCA. The next largest group is MSA. The next largest group is PSP.) The Ataxia Clinic has a DNA bank and works with two tissue banks.
Questions our patients ask:
* what do I have?
* what is the cause?
* are my children at risk?
* can it be cured?
* will it get worse?
* how bad will it get? how soon?
* is there any research?
Patients with ataxia coming on after 50 years of age might be misdiagnosed and in reality have an atypical parkinsonian disorder or Parkinson’s Plus.
Diagnosis can be made by
* symptoms, signs, rate of progression
* lab tests (MRI may be helpful)
* response to treatment
Symptoms that may occur in late-onset ataxia – usually from the cerebellum:
* staggering, wide-based walk (which means there is a risk of falling)
* incoordination of fine hand movements (which can include tremors with hand use)
* slurred or uneven speech
* jumpy, double vision, eye “tremors” (nystagmus)
* mild bladder control problems
Symptoms from the brainstem (midbrain, pons, medulla)
* reduced or slowed eye movement
* speech difficulties
* swallowing difficulties; risk of choking
* tightness of speech or breathing (called stridor)
* neck weakness
* spasticity of arms and legs
“Hot cross bun” sign – often appears on an MRI in MSA
Increased white shadows
In PSP on an MRI scan, the midbrain is atrophied
Symptoms from the basal ganglia (Parkinson’s symptoms):
* stiffness or rigidity of muscles
* freezing or slowed movements
* soft speech
Autonomic symptoms from the autonomic nervous system:
* orthostatic hypotension (significant fall in BP when standing), causing dizziness, blurred vision, lightheadedness
* trouble emptying urine in bladder
* male sexual dysfunction
Other symptoms that may sometime come on before the ataxia or years after the ataxia comes on:
* bladder urgency, often at night
* breathing problems at night, sleep apnea
* parasomnias, eg sleep talking, leg movements during sleep, vivid dreams, nightmares
* fatigue, slowed thinking, dementia
* depression or anxiety
* weight loss, bedsores, infection. These complications can lead to death.
In AD (Alzheimer’s Disease), there is atrophy in the front of the brain (in the cerebral cortex).
In CBD, there is atrophy in the back of the brain.
Rate of progression of symptoms can help determine the cause or uncover complications:
* Acute/rapid (overnight) – traumatic, vascular, metabolic/toxic, infectious, inflammatory causes
* Sub-acute (weeks or months) – post-traumatic, metabolic/toxic, infectious, neoplastic
* Slowly progressive (months to years) – atypical parkinsonism disorders fall into this category of progression
Everyone deserves testing for:
* which part of the brain is involved (MRI)
* medical factors (prior illnesses, toxic exposures, thyroid disease)
* immune or paraneoplastic
* possible genetic disease (SCA6 and FXTAS screening should always be given)
Why is there no family history of ataxia?
* no one asked
* information is unavailable (such as through adoption, loss of contact, non-cooperation, paternity issues)
* prior generations may have died before showing symptoms
* maybe it really is non-genetics
* a genetic counselor can help determine possible causes
Approach to late-onset predominantly cerebellar syndromes:
* use the history and neurological exam, imaging or other diagnostic tests
* detailed family and environmental history
* rule out genetic causes
* work with MD to minimize risks
Differential diagnosis: late-onset ataxia vs. Parkinson’s Plus
Late onset ataxia: slow progression
OPCA: slow progression
FXTAS: slow progression;
MSA-C: moderate progression (less than 10 years to wheelchair, especially if they have symptoms of PD)
PD: slow progression
Many times an MRI can can help diagnose these disorders
Environmental causes – pesticides, chemicals, vascular (stroke)
MSA and PSP have a possible response to levodopa. CBD has a poor response to levodopa.
MSA – most common form of Parkinson’s Plus or atypical PD
* all forms of MSA have symptoms of ataxia, Parkinson’s, and autonomic failure
* 80% start with parkinsonian symptoms, 20% start with cerebellar ataxia
25% of patients with sporadic cerebellar ataxia go on to develop MSA, within 5 years, especially if over 50 years.
The term OPCA has been used interchangeably for MSA-C but it is not the most accurate term.
18F-fluorodopa PET scan can be helpful in separating MSA for pure cerebellar ataxia.
When is MSA not the likely diagnosis:
* onset after age 75
* family history of ataxia or Parkinson’s
* classic pill-rolling rest tremor
* chorea (involuntary twitches)
* slowed or limited eye movement
Treatment of MSA:
* medications used to treat the symptoms become less effective as the disease progresses
* PT and OT always help
* levodopa and dopamine agonists are somewhat helpful for the slowness and stiffness of MSA but they may make low BP worse.
* OH can be treated with medications
* incontinence may be treated with bladder medication or catheterization
* constipation may be improved with dietary fiber or laxatives
* male impotence can be treated
* speech therapy may be able to help swallowing
* sleep disturbances may respond to medication or breathing devices
Once the causes are known, disease-modifying treatment and ultimately a cure will be possible
Neural replacement therapy (stem cell therapy and growth factor therapy) is under development
Active research study in South Korea on stem cell therapy for MSA: NCT00911365
She does NOT recommend any other stem cell programs at this time
Another useful website: hopes.stanford.edu/treatmts/index/trhome.html
Designed for Huntington’s Disease but has very useful info about medications and nutritional supplements
ClinicalTrials.gov studies on MSA:
* stem cell trial in South Korea
* rasagiline trial
* L-DOPS augmentation
Questions and Answers (by Dr. Perlman, unless indicated):
[Robin’s note: I’ve grouped the questions by topic — ataxia, OPCA, SCA, MSA-C, treatment, caregiving and support, and education.]
Q: Exactly what is ataxia?
A: Thinning of nerve cells of the cerebellum are usually seen on an MRI. There are many types of cerebellar ataxia (as we learned in the presentation).
Q: Is ataxia hereditary? Will my children get this? I am age 70, and have just been diagnosed with ataxia.
A: As this person is over 70, it’s unlikely that this is genetic. It’s unlikely it will turn in to MSA. She should have an MRI to look for signs of MSA. She should have testing for the two genes discussed earlier. Perhaps the cause of this person’s ataxia is nutritional imbalance, numbness of feet (causing imbalance), etc.
Q: My husband was diagnosed with ataxia. What type of ataxia is it?
A: It’s important to speak with the MD as to what evidence he/she has of the diagnosis. Even a simple brain MRI can help identify what type of ataxia it is. Blood work is helpful to know about vitamin deficiencies, poisons, etc. The patient must be proactive. The patient must know the terminology. The patient must actively pursue information and knowledge. 40% of people have genetic or inherited ataxias.
Q: I saw a general neurologist and got an ataxia diagnosis.
A: A general neurologist thinks of disorders associated with older people. A general neurologist may never have seen anyone with ataxia. A common misdiagnosis for someone over 50 or 60 is something other than ataxia. A general neurologist may miss blood pressure problems. If you have any question about your diagnosis, you should ask to be referred to an ataxia specialist or a movement disorder specialist.
The most common reasons for a misdiagnosis are:
* Inexperience on the part of the neurologist
* Tendency for the MD to think of the common things, and not the rarer things
* The MD not thinking of diagnostic tests that can be done
Q: [didn’t catch it]
A: 80% of what Dr. Perlman knows about ataxia she has learned from patients.
Q: Is all sporadic OPCA MSA-C? If so, why is the term OPCA still used?
A: The diagnosis OPCA came from looking at the brain on autopsies and on MRI scans. Atrophy was seen in certain areas of the brain. OPCA is basically an MRI diagnosis. OPCA isn’t the final diagnosis. 25% of those people with symptoms of cerebellar ataxia will go on to develop MSA. MSA-C is a separate condition. There may be common causes. The two terms are not interchangeable.
We don’t yet know how to identify these people in advance. Part of the research at UCLA is trying to understand why the 25% go on to develop MSA and why the other 75% do not.
Q: I have SCA6. What treatment is there? What about gabapentin? What about creatine?
A: There are many medications used to treat the symptoms of ataxia and eye tremors (nystagmus). Gabapentin can help with nystagmus. Creatine may protect nerves from deterioration. Creatine is an anti-oxidant.
The Stanford HOPES website has a complete list of supplements. Supplements or medications should be added one at a time.
Q: What is the status of gene therapy trials with SCA?
A: We are about 5 years away from human trials with gene therapy in SCA. Two avenues: blocking the bad gene and stimulating the good gene. To block the bad gene, we are using RNAi (a technique).
We are about one year away from human trials for another technique (histone acetylase inhibitors or something like that).
Q: What is the prognosis for SCA1? My son saw improvement with Chinese stem cell therapy.
A: SCA-type 1 slowly progresses with time. Most people with the genetic ataxias will progress over 15-25 years until they are completely disabled. The earlier a genetic ataxia comes on the more rapidly it progresses. For example, someone who gets SCA-type 1 in their 20s, might be disabled in their 30s.
She’s seen several cases who have been to China for stem cell therapy. The organization in China is not forthcoming. They have published nothing in reputable journals. They do not follow up with people so how can this organization know how these people are doing? Nerves grow and become stronger slowly. Don’t expect to see improvements in stem cell therapy for at least 6 months. Any improvements before six months are not from the stem cell therapy. The treatment in China includes other things such as acupuncture, Chinese herbs, etc. The benefits from that other treatment should decline upon leaving China. The Chinese organization does admit that those with genetic ataxias don’t derive as much benefit from the second and third rounds of stem cell treatment in China as they do from the first round.
Q: I have SCA-type 1. Is this the same as OPCA?
A: SCA-type 1 is a genetic form of ataxia. SCA-type 1 on an MRI shows thinning of the cerebellum. This is different from OPCA. OPCA is a general term. OPCA can have multiple causes.
Q: I have MSA-C. What is the latest research being done to treat and cure this disorder?
A: The oldest and largest research project to date is a natural history study being done in Europe and the US. In the US, the leader is Dr. Sid Gilman at the University of Michigan. The focus is finding the cause of MSA. We must first know the cause before we can know the cure.
See clinicaltrials.gov for MSA trials. The South Korean stem cell trial’s early results look very good. Work with your treating neurologist to find a promising study. Even if there’s no study near you, many of the drugs being studied in the trials can be tried off-label, under the direction of your physician.
Note that when you look on clinicaltrials.gov for multiple system atrophy, you will also see trials for multiple sclerosis (usually at the bottom of the list).
Q: I have MSA-C. What is 4-AP and will this help?
A: 4-AP is being developed by a company in Ireland for use in multiple sclerosis. This drug may be helpful for nystagmus. It is available now through compounding pharmacists (over the counter) but it should be used under an MD’s guidance. A serious side effect is epileptic seizures. This medication is similar to gapapentin. Hopefully this will be available by prescription soon. The compounded form available now may or may not be covered by insurance.
Q: Anything new about stem cell therapy?
A: There is now active research in the US on stem cells. We aren’t ready in the US for the sort of clinical trials that are going on in South Korea. You shouldn’t pay $30K for unproven stem cell therapy. Most funded research in the US allows patients to participate without charge.
She’s in favor of exploring alternative therapies — herbs, homeopathic therapies. These should be monitored by an MD. If in 6-12 months you don’t feel better from a therapy, you should discontinue and move on.
Q: What medications are used to treat depression?
A: Most anti-depressants affect the serotonin pathways. Others affect the adrenaline pathways. Lexapro is a very good drug but it doesn’t affect serotonin or adrenaline. If Lexapro doesn’t work, she tries Wellbutrin, Cymbalta, etc.
Q: I frequently undergo IVIG treatment and it seems to help my ataxia.
A: IVIG is immunoglobulin given intravenously. Perhaps this person’s ataxia is caused by the immune system. When the immune system is not involved, IVIG should not help. The immune system isn’t involved in a genetic form of ataxia.
Sometimes chemotherapy drugs are tried in those where the immune system is involved.
CAREGIVING AND SUPPORT
Q: What can I do to help my mother accept her condition?
A: Acceptance is a lot to ask of someone diagnosed with a neurodegenerative illness where the cause is unknown and there is no cure. There are amazingly strong individuals who are able to accept the diagnosis and take advantage of research. The encouragement of others with the same condition can be a strong motivation.
You have to encourage and support. Start with little steps — try PT, try exercising together.
MDs shouldn’t say “there’s nothing can be done.” There is a lot that can be done.
Q: It’s expensive to hire caregivers for someone. Is there help?
A: In short, no. Resources that are available include IHSS (in-home supportive services) in CA. There are some respite care grants. A few insurance companies are starting to cover nursing home care. Hospice care can be applied for and provides various levels of care in the home. It’s impossible to predict when someone is within six months of death. Hospice care can be renewed.
With proper care, we can put people on plateaus for long periods of time.
Q: How do I get a copy of the book you wrote?
A: The National Ataxia Foundation sponsored the development of a booklet on ataxia. It is written for physicians about diagnosing ataxia. Patients or family members will find it readable. Or take the booklet to an MD, PT, or OT and ask for an explanation.
For webinar participants, the National Ataxia Foundation will reduce the price and offer free shipping of this booklet. Send an email to Susan at the National Ataxia Foundation, [email protected], with “Dr. Perlman’s Book” in the subject line to take advantage of this offer.
Q: Can I get a copy of this presentation?
A (by the moderator): CurePSP is trying to make this presentation available. Maybe it can be emailed out. It will be available on the psp.org website later this year or early next year.
Q: Next webinars?
A: The next five will all be movement disorder specialists:
10/8 – Dr. Neal Hermanowicz, from UC Irvine – Fundamentals and diagnosis of PSP, CBD, and MSA
10/22 – Dr. Robert Hutchman – Interventions
11/5 – Dr. Yvette Bordelon – Latest research
11/19 – Dr. Lawrence Golbe – Research for dummies
12/3 – Dr. Panel of movement disorder specialists, led by Dr. Jerome Lisk