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Thymic malignancy is often associated with paraneoplastic neurological diseases (PNDs) and recognition of these disorders is important for physicians who treat these patients. The most common thymoma-associated PNDs are myasthenia gravis (MG), acquired neuromyotonia (Isaacs' syndrome), encephalitis, Morvan's syndrome, and myositis. Diagnosis of these disorders is complex but often aided by testing for specific autoantibodies, including those to the acetylcholine receptor for MG and to contactin-associated protein-like 2, protein of the voltage-gated potassium channel complex, in patients with acquired neuromyotonia, Morvan's syndrome, or encephalitis. Patients who manifest these disorders should be screened for thymoma at diagnosis, and worsening of these PNDs may be associated with recurrent thymoma. These disorders can cause profound disability but usually respond to immunotherapy, and often improve with thymoma treatment. Close cooperation among a team of specialists is required to take proper care of these patients.

Background Morvan’s syndrome is a rare disorder, characterized by peripheral nerve hyperexcitability, dysautonomia and encephalopathy with marked insomnia. About three quarters of patients have voltage gated potassium channel (VGKC) antibodies. A significant proportion of patients have associated tumours and the majority of these are thymomas. Introduction A 53 year-old man presented with a history of pain, cramps and twitching of the muscles of the chest and limbs, insomnia, hyperhidrosis, hypersalivation and cognitive impairment with hallucinations. Examination revealed fasciculations of the proximal upper limbs, piloerection of the forearms and mild postural hypotension. Investigations The patient underwent a number of electrophysiological studies: (1) EMG demonstrated spontaneous and frequent irregularly occurring neuromyotonic activity as doublet, triplet and multiplet single motor unit discharges firing at a high intraburst frequency (133–200 Hz), consistent with peripheral nerve hyperexcitability. (2) Paired-pulse transcranial magnetic stimulation revealed reduction in the short-interval intracortical inhibition (SICI) suggestive of central hyperexcitability. (3) EEG demonstrated left temporal slowing on an otherwise normal background. (4) autonomic testing showed a generalized sudomotor impairment consistent with autonomic dysfunction. Neuroimaging of the brain with PET demonstrated bilateral temporal lobe hypometabolism. Whole body PET revealed a hypermetabolic thyroid lesion, which was subsequently confirmed histologically to be a multifocal papillary thyroid carcinoma. Discussion The clinical and electrophysiological presentation was consistent with a diagnosis of Morvan’s syndrome in the context of a paraneoplastic phenomenon secondary to papillary thyroid cancer. The patient underwent a thyroidectomy and adjuvant radiotherapy. In addition, monthly intravenous methylprednisolone and intravenous immunoglobulin was instituted. Subsequently, the patient experienced significant symptomatic improvement with resolution of muscle fasciculations and cramps, hyperhidrosis and visual hallucinations. Insomnia and pain although improved did not completely resolve. Conclusion This case reviews the clinical and neurophysiological findings of Morvan’s syndrome. The case adds to the small number of non-thymomatous tumours associated with this syndrome and highlights the importance of a thorough search for malignancy in this clinical context.

Augustin Morvan (1819–1897) was a contemporary of Jean-Martin Charcot who practised medicine in rural Brittany. A perspicacious and astute clinician, he described three clinical pictures not previously isolated: in 1875 the semiology of myxoedema, in 1883 the neurological semiology of syringomyelia which he called “paretic analgesia of the upper extremities”, and finally in 1890 the semiology of “fibrillary chorea”, currently considered a model of synaptic pathology involving immunological damage to potassium channels and causing (as perfectly described by Morvan) myokymia, autonomic nervous system disturbances and agrypnia. “Fibrillary chorea” is today known as Morvan's syndrome and linked to limbic encephalitis.

A subgroup of limbic encephalitis is associated with antibodies against voltage-gated potassium channels (VGKC), and responds well to immuno-modulating therapies. Anti-VGKC antibodies are also found in Isaacs' syndrome and Morvan's syndrome, both of which are sometimes complicated by thymoma. We describe a 52-years-old man with limbic encephalitis, thymoma, and anti-VGKC antibodies, who presented with autonomic dysfunctions such as severe intestinal pseudo-obstruction, hyperhidrosis and hypertension. Thymectomy and corticosteroid therapy remarkably improved his symptoms. Brain magnetic resonance imaging showed hypothalamic lesions, in addition to the bilateral involvement of the medial temporal lobes. This patient had severe autonomic dysfunctions resembling those of Morvan's syndrome. This case may represent a subgroup of VGKC-antibody associated syndromes with a wide spectrum of symptoms, including Isaacs' syndrome, Morvan's syndrome, and limbic encephalitis.

Background Morvan's syndrome is characterized by peripheral nervous system hyperexcitibility (myokymia and neuromyotonia), hyperhydrosis, sleep disorder, limb paresthesias, and encephalopathy. Voltage gated potassium channel antibodies (VGKC abs) are frequently present. Reduplicative paramnesia (RP) has not been reported with this disorder. Objective To describe a patient with Morvan's syndrome presenting with RP. Design Single case study. Patient A 64-year-old man with several years of myokymia and myoclonus with escalating parasomnia and confusion developed the delusion that a replica of his house and its contents existed 40 mi away. Results Serum VGKC ab titer was elevated. Neuropsychological testing disclosed executive function and memory deficits. Electromyography demonstrated diffuse myokymia. Treatment with intravenous immunoglobulin and prednisone produced improvement of RP and myoclonus, but not myokymia. Conclusion RP may occur in patients with VGKC ab-associated Morvan's syndrome. Both RP and nervous system hyperexcitability may respond to immunotherapy including intravenous immunoglobulin and corticosteroids.

Autoantibodies against voltage-gated potassium channels (VGKC-Abs) are associated with acquired neuromyotonia (Isaacs' syndrome) and related disorders such as Morvan's syndrome and some cases of limbic encephalitis. The mechanisms underlying the various phenotypes induced by VGKC-Abs are not fully understood. Recently, we reported a case of LE with VGKC-Abs accompanied by severe intestinal pseudo-obstruction and thymoma. Thymectomy and immunosuppressive therapy induced dramatic clinical improvement of LE symptoms, and VGKC-Abs titers decreased from 1254 pM to 549 pM (normal>100 pM). Seventeen months later, the patient developed progressive generalized muscle cramping, paresthesias in his lower extremities, excessive sweating, and severe constipation. There was no recurrence of the LE. Electromyography showed fasciculation potentials and myokymic discharges, and the plasma VGKC-Abs titer was again elevated to 879 pM. Here we report a case of Isaacs' syndrome after complete remission of LE with VGKC-Abs that may provide an insight into a possible link among VGKC-Abs associated syndromes.