In a 60-year-old patient with progressive muscle spasms, limb rigidity, paresthesia, normal electrolyte panel, spasms that improve with baclofen, worsening of symptoms when lying still and attempting to sleep, requiring straight leg positioning at night, and no weakness, what is the most likely diagnosis and recommended management?

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Stiff-Person Syndrome (SPS) - Diagnosis and Management

This clinical presentation is highly suggestive of Stiff-Person Syndrome (SPS), and you should immediately check anti-GAD65 antibodies and obtain EMG to confirm continuous motor unit activity before escalating baclofen therapy.

Diagnostic Reasoning

The constellation of progressive muscle rigidity, stimulus-sensitive spasms (worse when lying still), tingling sensations, response to baclofen, normal strength, and normal electrolytes strongly points toward SPS rather than other spasticity disorders 1. The key distinguishing features are:

  • Stimulus-induced worsening: Symptoms triggered by lying still and attempting sleep are characteristic of SPS's heightened sensitivity to sensory stimuli 1, 2
  • Baclofen responsiveness: The partial improvement with baclofen supports a GABAergic dysfunction, which is the pathophysiologic hallmark of SPS 3
  • Absence of weakness: This excludes myopathy or motor neuron disease 1
  • Progressive rigidity with paresthesias: Classic for SPS presentation 4

Critical diagnostic tests needed immediately:

  • Anti-GAD65 antibody titers (serum and CSF) - positive in ~80% of classic SPS cases 1
  • EMG showing continuous motor unit activity at rest - pathognomonic for SPS 5, 2
  • Consider muscle biopsy only if GAD-negative to rule out inflammatory myopathy 6

Management Algorithm

First-Line Therapy (Current Stage)

Optimize oral baclofen dosing - The patient is already responding, indicating GABAergic therapy is appropriate 3. Baclofen is FDA-approved for spasticity and should be titrated to maximum tolerated dose (typically 60-80 mg/day in divided doses) 3.

Add high-dose benzodiazepines (diazepam 5-20 mg TID or clonazepam 0.5-2 mg TID) as these enhance GABA activity and are considered standard first-line therapy alongside baclofen 7, 8.

Second-Line: Immunotherapy

If symptoms remain refractory to oral GABAergic medications, initiate intravenous immunoglobulin (IVIG) therapy, as SPS is fundamentally an autoimmune disorder 7, 4. Standard dosing is 2 g/kg divided over 2-5 days, repeated monthly.

Third-Line: Intrathecal Baclofen Pump

For medically refractory cases, intrathecal baclofen (ITB) pump implantation provides the most definitive symptomatic control 8. The 2026 multicenter case series demonstrated sustained improvement in all six patients with severe SPS, with maintenance doses of 365-650 μg/day and durable benefit for 2.5-4 years 8.

Critical implementation points for ITB:

  • Perform a 4-day continuous intrathecal trial (not single-injection) starting at 50 μg/day and titrating to 150 μg/day to determine effective dose 6
  • This extended trial better predicts long-term success compared to single-bolus testing 6
  • ITB is effective even in GAD-negative SPS cases 6, 5
  • Expect significant functional improvement: patients transition from wheelchair-dependent to independent ambulation 7

Adjunctive Therapy

OnabotulinumtoxinA (Botox) injections into affected muscle groups can provide 3-month relief cycles and should be considered as adjunctive therapy, particularly for localized rigidity 4. A 2025 case report showed marked improvement in rigidity, posture, and ADLs with excellent safety profile 4.

Common Pitfalls to Avoid

  1. Don't mistake this for restless legs syndrome (RLS): While symptoms worsen at rest, RLS presents with an irresistible urge to move that relieves symptoms, whereas SPS causes painful rigidity that worsens with movement attempts. The 2025 AASM RLS guidelines 9 recommend gabapentin/pregabalin as first-line, but this patient's response to baclofen and lack of movement-relief pattern argues against RLS.

  2. Don't use baclofen for rheumatic muscle spasm: The FDA label explicitly states baclofen is NOT indicated for skeletal muscle spasm from rheumatic disorders 3. It's specifically for CNS-mediated spasticity.

  3. Monitor for baclofen withdrawal: Never abruptly discontinue oral baclofen, especially if transitioning to ITB, as withdrawal can cause seizures and hallucinations 3.

  4. Screen for ovarian cysts in women: Chronic baclofen use causes dose-related ovarian cysts in ~4% of patients; perform periodic pelvic examinations 3.

  5. Avoid dopamine agonists: While pramipexole and ropinirole might seem reasonable for movement disorders, the AASM now recommends against their standard use due to augmentation risk 9, and they have no role in SPS management.

Evidence Quality Note

The ITB recommendations are based on multiple case reports and a 2026 multicenter series 8 - the highest quality evidence available for this rare condition. The consistent dramatic functional improvements across all published cases (wheelchair to independent ambulation) 7, 6, 10, 5 make ITB the definitive therapy for refractory SPS, despite the lack of randomized trials given the disease rarity.

References

7
Research

Effectiveness of Intrathecal Baclofen for Intractable Stiffperson Syndrome: a Case Report.

Journal of rehabilitation medicine. Clinical communications, 2021

8
Research

Intrathecal Baclofen Pump Therapy for Medically Refractory Stiff Person Syndrome: A Multicenter Case Series.

Neuromodulation : journal of the International Neuromodulation Society, 2026

9
Guideline

treatment of restless legs syndrome and periodic limb movement disorder: an american academy of sleep medicine clinical practice guideline.

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2025

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.