Morvan's syndrome

Overview

Morvan’s syndrome, also known as Morvan's fibrillary chorea or Morvan's disease, is a rare autoimmune neurological disorder characterized by a combination of peripheral nerve hyperexcitability, autonomic dysfunction, severe insomnia, and neuropsychiatric symptoms. It is part of a group of disorders called autoimmune encephalitides and is often associated with antibodies targeting voltage-gated potassium channel (VGKC) complex proteins, particularly contactin-associated protein-like 2 (CASPR2).

The syndrome was first described in the 19th century by French physician Augustin Morvan. Although rare, Morvan’s syndrome can be life-threatening if untreated, but many cases show significant improvement with appropriate immunotherapy. It typically affects middle-aged to older men, but cases have also been reported in women and younger individuals.

Causes

Morvan’s syndrome is believed to be an autoimmune disorder, where the immune system mistakenly attacks the nervous system. The primary cause is the presence of autoantibodies against the CASPR2 protein, a component of the voltage-gated potassium channel (VGKC) complex involved in nerve signal regulation.

Common Causes and Triggers

• Autoantibodies: Especially anti-CASPR2 antibodies; occasionally associated with anti-LGI1 or other VGKC complex antibodies

• Paraneoplastic syndrome: Morvan’s syndrome can be associated with underlying tumors, particularly thymoma (tumor of the thymus gland)

• Idiopathic cases: In some patients, no specific trigger or underlying cause is identified

The immune response causes dysfunction in both the central and peripheral nervous systems, leading to the diverse range of symptoms seen in Morvan’s syndrome.

Symptoms

Morvan’s syndrome presents with a characteristic cluster of symptoms involving neuromuscular, autonomic, and central nervous system dysfunction. The severity and combination of symptoms vary, but the following features are commonly reported:

1. Peripheral Nerve Hyperexcitability (Neuromyotonia)

• Muscle twitching (myokymia)

• Muscle cramps and stiffness

• Fasciculations (visible muscle rippling)

• Hyperhidrosis (excessive sweating)

2. Autonomic Dysfunction

• Severe insomnia (agrypnia excitata)

• Profuse sweating (generalized or localized)

• Tachycardia or irregular heart rate

• Hypertension or blood pressure fluctuations

• Constipation or diarrhea

• Urinary retention or incontinence

3. Central Nervous System Involvement

• Hallucinations (visual or auditory)

• Delirium or confusion

• Memory impairment

• Agitation or aggression

• Seizures (occasionally)

4. Additional Findings

• Weight loss

• Fatigue and malaise

• Speech or swallowing difficulties (in advanced cases)

The hallmark of Morvan’s syndrome is the combination of neuromyotonia, autonomic instability, and severe sleep disturbances, often leading to complete insomnia that can persist for weeks or months.

Diagnosis

Diagnosing Morvan’s syndrome can be challenging due to its rarity and overlapping symptoms with other neurological conditions. A high index of suspicion, especially in patients with neuromyotonia and insomnia, is essential. Diagnostic steps include:

1. Clinical Evaluation

• Thorough history and physical examination focusing on neuromuscular and autonomic symptoms

• Assessment of cognitive function and psychiatric symptoms

2. Laboratory Tests

• Autoantibody testing: Detection of anti-CASPR2 antibodies in serum and cerebrospinal fluid (CSF); occasionally anti-LGI1 or other VGKC-complex antibodies

• Basic labs: To assess general health, inflammation, and organ function

3. Electrophysiological Studies

• Electromyography (EMG): Shows continuous muscle fiber activity consistent with neuromyotonia (fibrillations, fasciculations, myokymic discharges)

4. Imaging

• Brain MRI: May show changes related to encephalitis or be normal

• Chest CT/MRI: To search for underlying thymoma or other neoplasms

5. Sleep Studies

• May confirm severe reduction or absence of sleep (agrypnia)

Excluding other causes of neuromyotonia, encephalitis, and paraneoplastic syndromes is necessary for a confident diagnosis.

Treatment

Treatment of Morvan’s syndrome focuses on suppressing the autoimmune response, managing symptoms, and addressing any underlying tumor if present. Early and aggressive immunotherapy can significantly improve outcomes.

1. Immunotherapy

• Corticosteroids: Often first-line treatment to reduce inflammation

• Plasmapheresis or IVIG (intravenous immunoglobulin): Helps remove circulating antibodies

• Immunosuppressants: Such as azathioprine, cyclophosphamide, or rituximab in resistant cases

2. Tumor Management

• Thymectomy: Surgical removal of thymoma if detected can lead to significant symptom improvement or remission

3. Symptomatic Management

• Anticonvulsants or membrane-stabilizing drugs: Such as carbamazepine or phenytoin for neuromyotonia

• Benzodiazepines: May help with muscle symptoms and promote sleep

• Beta-blockers: For autonomic symptoms like tachycardia

• Psychiatric medications: For mood or psychotic symptoms (used cautiously)

Multidisciplinary care is often required, including neurology, immunology, psychiatry, oncology, and sleep medicine.

Prognosis

The prognosis of Morvan’s syndrome varies depending on the underlying cause and response to treatment. Many patients experience significant improvement or remission with immunotherapy, especially if treatment is initiated early. However, the course can be severe or even fatal if untreated or if there is delayed diagnosis.

Factors Influencing Prognosis

• Presence and successful removal of an underlying tumor (e.g., thymoma)

• Type and level of autoantibodies (anti-CASPR2-positive cases often respond well to treatment)

• Severity of autonomic and CNS involvement

• Timeliness and intensity of immunotherapy

With appropriate care, long-term remission is possible. Some patients may experience relapses and require ongoing immunosuppression. Lifelong monitoring is advised to manage recurrences and monitor for associated autoimmune or neoplastic conditions.