The National Institute of Neurological Disorders and Stroke (NINDS) describes multiple system atrophy (MSA) as a progressive neurological disorder with symptoms that reflect neurodegeneration in different parts of the nervous system. Neuron death in the central nervous system leads to motor dysfunction while neuron death in the autonomic nervous system leads to changes in involuntary bodily functions, like digestion and blood pressure. MSA is divided into two types, both of which present with autonomic dysfunction. The first presents with parkinsonism, called MSA-P. The other impacts cerebellar functions, like balance, called MSA-C. MSA is a rare disease, with estimates between 15,000 and 50,000 Americans.
Although rare, MSA can be difficult to diagnose, a challenge that researchers Deepmala Nandanwar and Daniel D. Truong of the Parkinson and Movement Disorder Institute investigate in new research. MSA is challenging to diagnose because it has a heterogeneous presentation, especially early in the disease course, with symptoms often closely resembling other movement disorders, like Parkinson’s disease. This makes a differential diagnosis challenging, leading to a problematic delay in diagnosis of MSA, including misdiagnoses. Many diagnostic tools are available, including MRIs, cardiac metaiodobenzylguanidine (MIBG) scans, dopamine transporter SPECT scan (DaTscan), and skin biopsy to detect phosphorylated alpha-synuclein. However, the authors of the study note that it is not always clear which test to use and when.
The authors state that “a timely diagnosis is important to enable patients and caregivers to plan their future; physicians can offer appropriate counseling and treatment to the patient with the correct diagnosis.” The authors propose a diagnostic algorithm for MSA, published in Clinical Parkinsonism & Related Disorders. Nandanwar and Truong stress that their algorithm is not meant to replace the Movement Disorders Society criteria for the diagnosis of MSA, but to supplement it in difficult cases.
In cases of suspected MSA-P or MSA-C, the authors recommend laboratory work to rule out other causes that are more common than MSA, such as diabetes, amyloidosis, or ataxia caused by drug or alcohol use. This initial differential diagnosis should be followed by brain imaging with MRI. Diffusion-weighted MRI can help differentiate MSA from Parkinson’s. However, MRI lacks sensitivity in key signs that can help positively diagnose MSA. This means that, while MRI is useful to differentiate from Parkinson’s, MRI should not be used to rule out MSA.
In cases of suspected MSA-P, the authors recommend a series of diagnostic tests to differentiate between different types of parkinsonism associated with MSA. First is the use of DaTscan, which can help to differentiate between either neurodegenerative parkinsonism or non-neurodegenerative parkinsonism. Next is the recommendation to test for the presence of phosphorylated alpha-synuclein, a key step in differentiating between synucleinopathies and tauopathies, two distinct etiologies of parkinsonism in MSA. The authors further note that detection of phosphorylated alpha-synuclein by skin biopsy is highly sensitive, even in the early stages of disease.
Next, MSA must be differentiated from Parkinson’s or dementia with Lewy bodies. This can include further examination of clinical features, additional brain scans, cardiovascular autonomic testing, and potentially a trial of levodopa therapy.
The authors conclude that “the diagnosis of MSA remains challenging despite two consensus MSA diagnostic criteria,” but contend that their algorithm can help guide the optimal use of the diagnostic tests currently available.
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Reference:
Nandanwar D, Truong DD. Multiple system atrophy: Diagnostic challenges and a proposed diagnostic algorithm. Clin Park Relat Disord. 2024;11:100271. doi: 10.1016/j.prdoa.2024.100271
Multiple system atrophy. National Institute of Neurological Disorders and Stroke. Accessed November 24, 2024. https://www.ninds.nih.gov/health-information/disorders/multiple-system-atrophy
Walsh RR, Krismer F, Galpern WR, et al. Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting. Neurology. 2018;90(2):74-82. doi:10.1212/WNL.0000000000004798
Low PA, Reich SG, Jankovic J, et al. Natural history of multiple system atrophy in the USA: a prospective cohort study. Lancet Neurol. 2015;14(7):710-719. doi:10.1016/S1474-4422(15)00058-7
