Can Multiple System Atrophy (MSA) cause restless legs syndrome or anxiety?

Multiple System Atrophy (MSA) and its Relationship to Restless Legs Syndrome and Anxiety

Yes, Multiple System Atrophy (MSA) can cause both restless legs syndrome and anxiety as part of its constellation of symptoms. 1, 2, 3

MSA and Restless Legs Syndrome

MSA is a progressive neurodegenerative disorder classified as a "Parkinson-plus" syndrome that involves abnormal accumulation of alpha-synuclein in oligodendroglia. It presents with various motor and non-motor symptoms beyond the classic triad of parkinsonism, cerebellar ataxia, and autonomic dysfunction 1.

Key points regarding MSA and restless legs:

• MSA can be subdivided into three clinical subtypes:

  • MSA-P: Predominant parkinsonian features
  • MSA-C: Predominant cerebellar symptoms
  • MSA-A: Predominant autonomic dysfunction (Shy-Drager syndrome) 1

• While not explicitly listed as a core feature of MSA, restless legs symptoms can occur as part of the broader spectrum of motor and sensory disturbances in MSA patients.

• The diagnostic criteria for Restless Legs Syndrome (RLS) include:

  • An urge to move the legs accompanied by uncomfortable sensations
  • Symptoms beginning or worsening during periods of rest
  • Relief with movement
  • Worsening of symptoms in the evening or night 4

• MSA patients often experience various motor symptoms that may overlap with or mimic RLS, particularly in the early stages of the disease 2.

MSA and Anxiety

Anxiety is a significant non-motor symptom in MSA:

• Research has demonstrated that MSA patients experience higher rates of anxiety compared to the general population 3.

• A 2018 study specifically found that MSA-P patients (those with predominant parkinsonian features) had higher anxiety scores on the Hamilton Anxiety Scale compared to MSA-C patients 3.

• Anxiety in MSA patients contributes significantly to decreased health-related quality of life, as confirmed by regression analysis showing anxiety as an independent predictor of decreased quality of life 3.

Clinical Implications and Management

For patients with MSA experiencing restless legs or anxiety:

• Diagnostic Considerations:

  • Evaluate for RLS using established diagnostic criteria and tools such as the RLS Diagnostic Index (sensitivity 93%, specificity 98.9%) 4
  • Distinguish RLS from other conditions with similar presentations (peripheral neuropathies, vascular disease, nocturnal leg cramps) 4
  • Consider laboratory evaluation including ferritin levels, as iron deficiency can exacerbate RLS symptoms 4

• Management of RLS in MSA:

  • First-line pharmacological treatment: Alpha-2-delta ligands (pregabalin or gabapentin) 4
  • Second-line: Dopamine agonists (with caution due to risk of augmentation) 4
  • Non-pharmacological approaches: Regular exercise, smoking cessation, alcohol avoidance, caffeine reduction 4

• Management of Anxiety in MSA:

  • Address anxiety as it significantly impacts quality of life 3
  • Consider both pharmacological and non-pharmacological approaches
  • Regular monitoring of anxiety symptoms as part of comprehensive MSA care

Important Caveats

• MSA is a progressive disorder with a mean disease duration of approximately 6 years from onset 1.

• The presence of RLS or anxiety symptoms in a patient with suspected MSA should prompt comprehensive evaluation for other characteristic features of MSA, including autonomic dysfunction, parkinsonism, and cerebellar signs 1, 2.

• Patients with MSA-P tend to have more severe motor impairment, depression, anxiety, cognitive impairment, and lower quality of life than those with MSA-C 3.

• When managing MSA patients with RLS symptoms, be aware that dopamine agonists (commonly used for RLS) must be used cautiously due to potential exacerbation of orthostatic hypotension, which is already a problem in MSA 4.

• Regular monitoring for disease progression and symptom management is essential for optimizing quality of life in MSA patients 3.