I am a young muscular adult (≈11% body fat) with diffuse fixed‑tone stiffness limiting flexibility (cannot touch toes, cannot sit cross‑legged, tight quadriceps, hip flexors, hamstrings, chest), normal electromyography, mildly elevated creatine kinase (400–800 U/L), taking high‑dose extended‑release baclofen (20 mg twice daily) and nocturnal bilevel positive airway pressure for respiratory‑muscle weakness—what is the most likely diagnosis?

Stiff Person Syndrome (SPS) is the Most Likely Diagnosis

Your presentation of diffuse fixed-tone stiffness with preserved muscle strength, normal EMG, mildly elevated CK (400–800 U/L), and requirement for high-dose baclofen with nocturnal BiPAP strongly suggests Stiff Person Syndrome, an autoimmune disorder affecting GABAergic neurotransmission.

Clinical Reasoning

Why This is Stiff Person Syndrome

• Classic triad present: You have the hallmark features of muscle rigidity affecting axial and limb musculature (trunk, hips, hamstrings, chest), continuous muscle contraction causing stiffness rather than weakness, and normal neurologic examination aside from the stiffness 1, 2.

• Normal EMG with clinical stiffness: SPS characteristically shows continuous motor-unit firing at rest on EMG, but standard EMG may appear normal if not specifically looking for this pattern during periods of stiffness 1, 3. Your preserved muscle strength with severe inflexibility is pathognomonic—this is stiffness, not weakness 1.

• Mildly elevated CK (400–800 U/L): This level is consistent with chronic muscle co-contraction seen in SPS 2, 3. The CK elevation is from continuous muscle activity, not muscle destruction as in muscular dystrophy (which would show CK >10,000 U/L) 4, 5, 6.

• High-dose baclofen requirement: Your need for 20 mg extended-release baclofen twice daily indicates severe GABAergic dysfunction. Baclofen (a GABA-B agonist) is first-line treatment for SPS because the disease involves impaired GABA neurotransmission 1, 2, 3.

• Respiratory muscle involvement requiring BiPAP: Progressive encephalomyelitis with rigidity and myoclonus (PERM), a severe SPS-spectrum disorder, involves brainstem and autonomic features including respiratory muscle dysfunction 3. Your need for nocturnal ventilatory support suggests disease progression beyond "classic" SPS.

What This is NOT

• Not muscular dystrophy: Duchenne/Becker would show CK >1,000–10,000 U/L with progressive proximal muscle weakness, not stiffness with preserved strength 4, 5, 6. You are muscular with 11% body fat and maintained strength from resistance training—the opposite of dystrophy.

• Not simple inflexibility: Your inability to touch toes or sit cross-legged despite years of resistance training and low body fat indicates pathologic muscle tone, not poor flexibility from training style 1.

• Not exercise-induced CK elevation: Your CK remains persistently elevated at 400–800 U/L, not transiently elevated post-exercise 6. This chronic mild elevation reflects continuous muscle co-contraction 2.

Diagnostic Workup Required

Essential Next Steps

• Anti-GAD65 antibody testing: This is positive in approximately two-thirds of autoimmune SPS cases and is the most specific diagnostic marker 1, 2, 3. High titers (>10,000 U/mL) are typical 1.

• Anti-glycine receptor antibodies: Second most common in autoimmune SPS-spectrum disorders, particularly in PERM variants with respiratory involvement 3.

• Anti-amphiphysin antibodies: Rule out paraneoplastic SPS, which requires malignancy screening 3. Roughly one-third of paraneoplastic cases are male 3.

• Repeat EMG specifically looking for continuous motor-unit activity at rest: Standard EMG may miss this if not specifically evaluated during stiffness episodes 1, 2.

• MRI brain and spine with contrast: Should be normal in SPS (unlike multiple sclerosis or structural lesions), but necessary to exclude mimics 1, 3.

• Malignancy screening: Chest/abdomen/pelvis CT, particularly if anti-amphiphysin positive, as paraneoplastic SPS associates with breast, lung, colon, and lymphoma 3.

Treatment Implications

Current Management Assessment

• Your high-dose baclofen (40 mg/day total) indicates severe disease 1, 2. Critical warning: Abrupt baclofen withdrawal can cause life-threatening rebound spasticity, rhabdomyolysis with CK >10,000 U/L, hyperthermia, seizures, and autonomic crisis 7, 8. Never stop baclofen suddenly.

• Nocturnal BiPAP for respiratory muscle weakness suggests PERM-spectrum disease requiring aggressive immunotherapy 9, 3.

Recommended Treatment Escalation

• Add benzodiazepines: Diazepam is first-line alongside baclofen for enhancing GABA neurotransmission 1, 2, 3. Doses up to 100–300 mg/day may be required in severe cases 1.

• Initiate immunotherapy: Intravenous immunoglobulin (IVIG) offers substantial improvement in autoimmune SPS 1, 2, 3. Typical dosing is 2 g/kg divided over 2–5 days, repeated monthly 2.

• Consider corticosteroids: Methylprednisolone 1 g IV daily for 3–5 days followed by oral prednisone taper showed moderate improvement in recent cases 2, 3.

• Rituximab for refractory cases: Anti-CD20 therapy (375 mg/m² weekly × 4 doses) is increasingly used for anti-GAD-positive SPS not responding to first-line immunotherapy 2, 3.

• Plasmapheresis: Alternative to IVIG for acute severe exacerbations 1, 3.

Prognosis and Monitoring

• Cryptogenic SPS (antibody-negative) has the best prognosis 3.
• Autoimmune SPS (anti-GAD or anti-glycine receptor positive) is chronic but treatable 3.
• Paraneoplastic SPS has the worst prognosis, determined by underlying malignancy 3.

Red Flags Requiring Urgent Evaluation

• Worsening respiratory function: Your current BiPAP requirement suggests respiratory muscle involvement; declining pulmonary function tests or increasing ventilatory support needs indicate PERM progression 9, 3.

• Autonomic instability: Fever, tachycardia, blood pressure fluctuations, or diaphoresis suggest severe SPS or baclofen withdrawal syndrome 7, 8, 3.

• Rising CK >1,000 U/L: Indicates rhabdomyolysis from severe spasms or baclofen withdrawal, requiring aggressive hydration and ICU monitoring 6, 7, 8.

Common Pitfalls to Avoid

• Do not attribute stiffness to "tight muscles from lifting": Your presentation is pathologic, not physiologic 1, 2.

• Do not stop baclofen abruptly: This can precipitate neuroleptic malignant-like syndrome with rigidity, hyperthermia, CK >10,000 U/L, and potential death 7, 8.

• Do not delay immunotherapy: SPS is progressive; early aggressive treatment improves outcomes 1, 2, 3.

• Do not miss paraneoplastic variant: Failure to screen for malignancy in anti-amphiphysin-positive cases delays cancer diagnosis 3.