Brain Matters

"Recent developments in multiple system atrophy."

Journal of Neurology. 2009 May 27.
Gregor K. Wenning and Nadia Stefanova
Section of Clinical Neurobiology, Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
PubMed ID# 19471850

Here are some excerpts and highlights:

* The authors think we've learned a great deal about MSA between 1969 and the present.

* Autonomic failure is universal in MSA-P and MSA-C.

* Not all sporadic OPCA is MSA-C.

* "The revised consensus criteria regard dementia as a non-supportive feature of MSA. However, recent evidence suggests that dementia can occur in some patients otherwise satisfying the MSA criteria. Further studies are required to assess the frequency and profile of dementia in MSA. These data may support a broader phenotype of MSA that also includes cognitive dysfunction."

* Lots is going on in the area of neuroimaging.  With regard to advanced MRI techniques:  The "MR parkinsonism index that is based on measurements of pons, midbrain, middle and superior cerebellar peduncle, has been proposed to differentiate PSP from PD and MSA-P cases."

"Diffusion-weighted imaging (DWI) has been shown to differentiate MSA-P from PD and control subjects (but not from PSP)...   In contrast, rADCs [regional apparent diffusion coefficient] of the middle cerebellar peduncle allowed the separation of MSA-P and PSP patients. Finally, patients with early-stage MSA-C were discriminated from controls..."

* But functional imaging (eg, PET and SPECT) seems superior to MRI:  "Recently, a comparative study on MRI and 18F-fluorodeoxyglucose PET showed that the latter is more sensitive than MRI in differentiating PD from MSA-P."

Brain "perfusion SPECT shows striatal hypoperfusion in MSA-P that distinguishes this disorder from PD. Perfusion SPECT, when coupled with classic MRI, shows high sensitivity and specificity in differentiating MSA from PD."

* "Recently, transcranial ultrasound was shown to discriminate PD from MSA and PSP. The hyperechogenicity of substantia nigra is typical of PD, whereas the hyperechogenicity of the lenticular nucleus associated with a normal echogenicity of substantia nigra suggests an atypical parkinsonism diagnosis. The discriminant value of transcranial sonography seems higher in cases of disease onset under 60 years. Transcranial ultrasound has been tested in the diagnosis of parkinsonian syndrome at early stages of the disease, suggesting that this technique could really help uncertain clinical diagnosis."

* The causes of MSA are unknown though it is assumed that a "complex interaction of genetic and environmental mechanisms seems likely. However, due to principal limitations of environmental studies...there are no convincing findings. Mercury, methanol, carbon tetrachloride, carbon disulfide, and cyanide have been associated with MSA-like parkinsonian disorders in a small series of cases. Further, manganese intoxication reported in miners can produce clinical, neuroimaging, and pathological findings that may overlap with those of MSA. The few controlled studies available in the literature have attempted to correlate the increased risk of MSA with occupational and daily habits, such as working exposure to solvents, plastic monomers, additives, metals and various other toxins, and history of farming. However, the increased risk of MSA related with occupation and pesticides has not been confirmed by a recent study."

* "Smoking appears to be a protective factor for MSA as in PD... Alcohol consumption showed no association in an earlier study but it was protective in a more recent one."

* "During the last years, polymorphisms of several genes involved in inflammatory processes have been associated with an elevated MSA risk."

* "L-Dopa is widely regarded as the antiparkinsonian therapy of choice in MSA, although a randomized controlled trial of L-Dopa has never been performed. Although MSA patients are commonly believed to be non- or poorly-responsive to dopaminergic therapy, efficacy has been documented in up to 40%, often lasting for up to a few years. ... L-Dopa responsiveness should be tested by administering escalating doses over a 3-month period up to a least 100 g per day (if necessary and if tolerated). L-Dopa-induced induced dyskinesias affecting orofacial and neck muscles occur in 50% of MSA-P patients, sometimes in the absence of motor benefit."

* There were disappointing results with a "short-term open trial with amantadine at high doses (400-600 600 mg/day) in five patients with MSA [who were] unresponsive to L-Dopa."

* There was improvement in motor symptoms in a double-blind placebo-controlled randomized trial with 19 MSA patients and Paxil 30 mg three times/day.

* "[Bilateral] subthalamic stimulation has been reported beneficial in four patients with MSA-P though a poor response was seen in other cases."

* The authors seem to recommend botox injections for orofacial dystonia, limb dystonia, and drooling, but recommend against botox for disproportionate antecollis.

* "Midodrine showed significant benefit in randomized placebo-controlled trials in patients with OH but may exacerbate urinary retention."

* "Inspiratory stridor develops in about 30% of patients."

* "Psychological support for patients and partners needs to be stressed."

* There were disappointing results from some recent studies of recombinant human growth hormone (r-HGH), minocycline, and riluzole.

* "In a recent study in transgenic MSA mice, rasagiline has proven to be a potent neuroprotective candidate for MSA, inducing behavioural improvement as well as preservation of neurons... Presently, a clinical trial with rasagiline in MSA is under discussion."

* "Mesenchymal stem cells (MSCs) are under discussion as a candidate source for brain repair in MSA based on the recent report of Lee and co-workers, who suggested disease progression delay in MSA patients receiving MSC implantation. However, more preclinical work is needed to confirm this effect as well as to define the underlying mechanisms of action."