This medical journal article on current and future approaches to the management of MSA was published in July 2010 but the abstract was just recently posted to PubMed. The article reviews current symptomatic treatment, potential neuroprotective drugs, and future approaches to the management of MSA. It was written by a French team of neurologists.
Wonderfully, the full article is available at no charge online via PubMed:
www.ncbi.nlm.nih.gov/pmc/articles/PMC3002658/
Therapeutic Advances in Neurological Disorders. 2010 Jul;3(4):249-63.
Multiple system atrophy: current and future approaches to management.
Flabeau O, Meissner WG, Tison F.
Department of Neurology, University Hospital of Bordeaux, Bordeaux, France.
Here are a few notes:
CURRENT TREATMENT
There is a nice table (Table 1) of current first-line treatment for various symptoms and alternative treatments. I thought one symptom made no sense to include and its treatment also made no sense: the treatment for “cognitive impairment” is “speech therapy.” Table 1 is a good summary of all the first half of the article. In the article, it seems that what is meant by “cognitive impairment” is “verbal fluency”; I’m unclear if speech therapy will help with verbal fluency.
Here’s a very short summary of the current treatments:
“Current symptomatic management in MSA should target motor impairment, autonomic failure and depression, as these features are associated with a poor quality of life. Levodopa remains the main treatment for MSA, despite its modest and nonsustained effect. Among the several treatments available for OH, only midodrine meets the criteria of evidence-based medicine. Strategies for urinary disorders are well standardized, while other symptoms such as breathing disorders, RBD, depression or dystonia remain out of consensus.”
Here are some things I learned from the current treatment section of the article:
* “Although levodopa induces less delirium and hallucinations in MSA than in PD, it can lead to adverse effects such as … pathological hypersexuality.”
I hear from many PD caregivers about Sinemet causing hypersexuality but I’ve never heard this from MSA caregivers.
* “According to consensus criteria, levodopa unresponsiveness should only be accepted after a treatment with at least 1 g of levodopa per day for at least 3 months.”
* “Clean intermittent self- catheterization (CISC) is recommended as the first-line treatment when the postvoid residual is above 100 ml. Thus, the residual volume should be regularly monitored, for example with a portable ultrasound device. The critical threshold of 100 ml is reached in a mean of 2 years after disease diagnosis.”
* “To reduce the risk of infection due to permanent catheterization, surgery such as sphincterotomy or sphincteric wall stenting can be considered as a last option in MSA” [for the treatment of urinary incontinence].
* RBD (REM sleep behavior disorder) “is observed in 69-100% of systematic polysomnography recordings in MSA patients.”
NEUROPROTECTIVE STRATEGIES
All clinical trials investigating neuroprotective strategies — riluzole, minocycline, growth hormone, and estrogen (tested in MSA-C only) — have failed to show any disease-modifying benefits. The authors advocated for further trials of growth hormone at higher doses and with more patients.
FUTURE THERAPIES
For neuroprotection, several drugs are being tested in MSA: lithium, rasagiline, and intravenous immunoglobulins. The lithium study is taking place in Italy. The rasagiline (Azilect) trial has been going on in the US for a year or more.
The IVIg trial is going on at the University of Massachusetts (Peter Novak, MD, PhD is the principal investigator). The authors say: “a former clinical report [on IVIg] does not support any therapeutic effect in MSA.”
The authors mention rifampicin (“no human trial has been yet planned”) and NSAIDs (“the harmful adverse effects of long-term use may limit their evaluation until the development of safer drugs”).
For neurorestoration, three treatments are described:
* transplantation of fetal dopaminergic cells
* injection of bone marrow mesenchymal stem cells
* injection of granulocyte colony stimulating factor (GCSF)
In the “Future Therapies” section, the authors discuss the importance of researching unexplained sudden death in MSA. The authors say: “Occurrence of sudden death is a common cause of mortality in MSA and may happen in the early stages while disability remains acceptable. The origin of sudden death in MSA remains unknown, although clinical reports, experimental and neuropathological evidence suggest that respiratory dysfunction may be the leading cause.”
The importance of the clinical diagnostic criteria and biomarkers is discussed.
Robin