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Phenotype-supported diagnosis and combined immunotherapy improve sleep and neuromuscular symptoms in seronegative Morvan syndrome

A 63-year-old man with seronegative Morvan syndrome presenting with agrypnia excitata (2-3 h/night sleep, ISI 24/28) and peripheral nerve hyperexcitability was treated with combined immunotherapy (intravenous methylprednisolone, prednisone taper, azathioprine) and symptomatic therapy (carbamazepine, melatonin). At 6 months, sleep restored to 7-8 h/night, ISI decreased from 24 to 4, MRC sum score improved from 48 to 58/60, and CK dropped from 928 to 185 U/L.

Last updated: Jul 30, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score32/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Seronegative Morvan Syndrome Presenting With Agrypnia Excitata and Peripheral Nerve Hyperexcitability: A Phenotype-Supported Diagnostic and Therapeutic Approach in a Resource-Limited Setting.

observational

Taha HM, Taha KH · Clinical case reports (2026)

Participants: N/A
Duration: 6 months
Intervention: Combined immunotherapy (intravenous methylprednisolone, prednisone taper, azathioprine) plus symptomatic treatment (carbamazepine, melatonin)
Outcome: Sleep duration, Insomnia Severity Index (ISI), Medical Research Council (MRC) sum score, creatine kinase (CK) levels
Effect Size: N/A
Population: 63-year-old Palestinian man with seronegative Morvan syndrome (complete clinical triad: neuromyotonia, agrypnia excitata, dysautonomia)

Result:

PubMed: 42487658DOI: 10.1002/ccr3.73196

Mechanism Graph

Immunotherapy suppresses autoimmune-mediated neuronal hyperexcitability
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Carbamazepine reduces peripheral nerve hyperexcitability
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Melatonin promotes sleep regulation
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Result: Resolution of insomnia, neuromyotonia, and autonomic symptoms

Limitations

  • ⚠Single case report with no control group
  • ⚠Resource-limited setting may limit generalizability to centers with biological therapies

Frequently Asked Questions

What is agrypnia excitata?▼

Agrypnia excitata is a severe insomnia phenotype characterized by near-total sleep loss, motor agitation, and autonomic hyperactivity, often seen in Morvan syndrome.

How was seronegative Morvan syndrome diagnosed in this case?▼

Diagnosis was based on the complete clinical triad (neuromyotonia, agrypnia excitata, dysautonomia), EMG findings (myokymic and neuromyotonic discharges), and exclusion of mimics, despite negative CASPR2 and LGI1 antibodies.

What treatments were effective in this patient?▼

Combined immunotherapy (methylprednisolone, prednisone, azathioprine) and symptomatic drugs (carbamazepine, melatonin) led to marked improvement in sleep, muscle strength, and CK levels at 6 months.

What is the prognosis for seronegative Morvan syndrome?▼

This case suggests that phenotype-supported diagnosis and immunotherapy can yield significant clinical improvement even in seronegative cases and resource-limited settings.

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References

  1. 1.Taha HM, Taha KH. "Seronegative Morvan Syndrome Presenting With Agrypnia Excitata and Peripheral Nerve Hyperexcitability: A Phenotype-Supported Diagnostic and Therapeutic Approach in a Resource-Limited Setting.." Clinical case reports, 2026. PMID: 42487658 DOI: 10.1002/ccr3.73196
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.