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A 56-year old man, originally from Pakistan, presented with bilateral avascular necrosis of the hips on a background of emphysema, pulmonary fibrosis, coronary artery disease, diabetes type 2 and psoriasis. The cause of the avascular necrosis was unclear, with no recent trauma or steroid use. During his preoperative consultation, he presented dysautonomia requiring an inpatient investigation; the surgery was canceled. He reported a thirty-pound weight loss and a three-week history of night sweats and shortness of breath. While hospitalized, this gentleman presented subacute confusion and fluctuation of his sensorium, compatible with limbic encephalitis. Furthermore, he developed diffuse myokymia involving the axial and appendicular musculature, confirmed by EMG.

Morvan's syndrome is a rare syndrome of likely autoimmune etiology characterized by peripheral nerve hyperexcitability, dysautonomia, insomnia, and fluctuating delirium with prominent hallucinations. Since its first mention in 1890, less than 100 cases have been described in literature. The largest existing review includes details of 29 cases. This case series describes 4 cases (M = 4) of Morvan's syndrome which presented between May and November 2017 to a single tertiary care referral teaching hospital in north India. All the four patients manifested behavioral abnormalities, sleep disturbances, hallucinations, autonomic dysfunction, and clinical signs of peripheral nerve hyperexcitability, mostly as myokymia. Two of the patients had Anti-CASPR2 (contactin-associated protein 2) antibodies. Three of them had electromyography features of peripheral nerve hyperexcitability and only one had elevated cerebrospinal fluid protein level. We hypothesize that Morvan's syndrome and other less characterized autoimmune encephalitis/peripheral nervous system syndromes may have infectious triggers. A possible viral trigger may result in generation of autoantibodies which result in the typical manifestations. We base these hypotheses on the finding of four cases of an orphan disease within a short period of time in a limited geographical distribution.

Morvan's syndrome (MoS) is a rare, complex neurological disorder characterized by neuromyotonia, neuropsychiatric features, dysautonomia and neuropathic pain. The majority of MoS cases have a paraneoplastic aetiology, usually occurring prior to the diagnosis of the underlying tumour and showing improvement following its treatment. The present study reports the case of a 35-year-old Caucasian male patient who was diagnosed with stage IVA thymoma. Thymectomy, lung resection, diaphragmatic pleurectomy and pericardio-phrenectomy were performed 6 months after neoadjuvant chemotherapy. The pathological evaluation revealed a type B2-B3 thymoma with focal squamous differentiation. Two years later, the patient underwent new surgical treatment for a local recurrence of the same histological type, and 4 weeks later, the patient presented with complex neurological symptoms compatible with MoS, including neuromyotonia, neuropsychiatric features, dysautonomia and neuropathic pain. Electromyography was compatible with a diagnosis of neuromyotonia. Brain magnetic resonance imaging scan and tests for serum anti-acetylcholine receptor, anti-striated muscle antibodies and anti-30-kDa titin fragment antibodies were all negative, whereas tests for anti-voltage-gated potassium channel (VGKC)-complex antibodies (333.3 pmol/l), anti-leucine-rich glioma inactivated protein 1 and anti-contactin-associated protein-like 2 antibodies were positive. The patient underwent 3 cycles of intravenous administration of immunoglobulins (0.4 g/kg/day for 5 days every 4 weeks) with little clinical and electrophysiological improvement. We speculated that the late onset of the symptoms in the present patient may have been triggered by an increase in the serum level of anti-VGKC antibody, which was caused by the surgery performed for the treatment of recurrent thymoma. To the best of our knowledge, the present report is the first case of MoS associated with this histological type of thymoma uncommonly occurring upon surgical treatment of recurrent thymoma.

Morvan's syndrome is an autoimmune disorder of peripheral and central nervous system mediated by VGKC antibody. Here we report a case of Morvans syndrome who presented 1 month after ayurvedic drug intake. She presented with symptoms of peripheral nerve hyperexcitablity and autoimmune testing revealed positive result for VGKC antibody. Heavy metals level was also significantly raised. She improved after a course of steroids. This case report tries to highlight the association of VGKC mediated Morvans syndrome with heavy metal poisoning and its incidental occurence after Ayurvedic drug intake.

REM sleep behavior disorder (RBD) may occur acutely or subacutely, irrespective of age and sex. RBD or isolated REM sleep without atonia (RSWA) has been associated with various medications, or substance use/abuse, or abrupt withdrawal states. Less frequently, structural brain lesions (vascular, demyelinating disease, tumors), especially in the pontine region, may cause acute RBD. Also, RBD can appear acutely after a stressful life event and in post-traumatic stress disorder. RBD recognition in all these clinical conditions has a clinical value, but could have also a crucial importance in understanding the pathophysiology of RBD. More awareness of the existence of acute forms of RBD and greater familiarity with the various potential clinical pictures may help to avoid misdiagnoses and mistreatments. In addition, if prospective studies will confirm the existence of separate RBD patient subgroups (e.g., older men with neurodegenerative diseases, younger patients with narcolepsy, middle-aged women with depression taking antidepressants, and patients with autoimmune diseases), then prognostic differences and optimal treatments across RBD subgroups could emerge.

Peripheral nerve hyperexcitability (PNH) syndromes are an uncommon group of conditions characterised by spontaneous discharges from motor nerve fibres. These are largely immunological (sometimes secondary to neoplasm like thymoma), and some forms are known to be genetic. Sometimes, they can be secondary to neuropathic or anterior horn cell disease. Electrophysiology shows myokymia or neuromyotonia, and antibodies against voltage-gated potassium channel are often detected. Immunotherapy leads to favourable outcomes, and hence it is important to know about these uncommon conditions.

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.

Morvan’s syndrome is a rare autoimmune disorder characterized by triad of peripheral nerve hyperexcitability, autonomic dysfunction, and central nervous system symptoms. Antibodies against contactin-associated protein-like 2 (CASPR2), a subtype of voltage-gated potassium channel (VGKC) complex, are found in a significant proportion of patients with Morvan’s syndrome and are thought to play a key role in peripheral as well as central clinical manifestations. We report a patient of Morvan’s syndrome with positive CASPR2–anti-VGKC antibody having syndrome of inappropriate antidiuretic hormone as a cause of persistent hyponatremia.

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.

Objective: A study was undertaken to describe the clinical spectrum, voltage-gated potassium channel (VGKC) complex antibody specificities, and central nervous system localization of antibody binding in 29 patients diagnosed with Morvan syndrome (MoS). Methods: Clinical data were collected using questionnaires. Radioimmunoassay, cell-based assays, and mouse brain immunohistochemistry were used to characterize the serum antibodies. Results: Neuromyotonia (100%), neuropsychiatric features (insomnia 89.7%, confusion 65.5%, amnesia 55.6%, hallucinations 51.9%), dysautonomia (hyperhidrosis 86.2%, cardiovascular 48.3%), and neuropathic pain (62.1%) were the most common manifestations. A total of 93.1% of MoS patients were male. VGKC-complex antibodies were present in 23 of 29 (79%) MoS patients at referral; 24 of 27 available sera had CASPR2, LGI1, or both CASPR2 and LGI1 antibodies (3 also with contactin-2 antibodies). CASPR2 antibodies were generally higher titer than LGI1 antibodies. Tumors (41.4%), mainly thymomas, were associated with CASPR2 antibodies and a poor prognosis, whereas LGI1 antibodies were associated with serum hyponatremia. In brain tissue regions including the hypothalamus, raphe, and locus coeruleus, commercial antibodies to LGI1 bound to neuronal cell bodies including the antidiuretic hormone-secreting and orexin-secreting hypothalamic neurons, whereas CASPR2 commercial antibodies bound more often to the neuropil. MoS antibodies bound similarly, but there was evidence of additional antibodies in some sera that were not adsorbed by LGI1- or CASPR2-expressing cells and bound to mouse Caspr2−/− tissue. Interpretation: MoS is clinically distinct from other VGKC-complex antibody-associated conditions, and usually is associated with high-titer CASPR2 antibodies, often accompanied by lower-titer LGI1 antibodies. CASPR2 and LGI1 antibodies bind to multiple brain regions, which helps to explain the multifocal clinical features of this disease, but other antibodies are likely to play a role in some patients and need to be characterized in future studies. ANN NEUROL 2012

Patients presenting with subacute amnesia are frequently seen in acute neurological practice. Amongst the differential diagnoses, herpes simplex encephalitis, Korsakoff's syndrome and limbic encephalitis should be considered. Limbic encephalitis is typically a paraneoplastic syndrome with a poor prognosis; thus, identifying those patients with potentially reversible symptoms is important. Voltage-gated potassium channel antibodies (VGKC-Ab) have recently been reported in three cases of reversible limbic encephalitis. Here we review the clinical, immunological and neuropsychological features of 10 patients (nine male, one female; age range 44-79 years), eight of whom were identified in two centres over a period of 15 months. The patients presented with 1-52 week histories of memory loss, confusion and seizures. Low plasma sodium concentrations, initially resistant to treatment, were present in eight out of 10. Brain MRI at onset showed signal change in the medial temporal lobes in eight out of 10 cases. Paraneoplastic antibodies were negative, but VGKC-Ab ranged from 450 to 5128 pM (neurological and healthy controls

Morvan syndrome is characterized by central, autonomic, and peripheral hyperactivity. Examples of central hyperactivity include confusion, memory problems, hallucinations, insomnia, and myoclonus; examples of autonomic hyperactivity include hyperhidrosis and fluctuations in blood pressure; examples of peripheral hyperreactivity include clinical or electrophysiological evidence of painful cramps, myokymia, and neuromyotonia. We present a typical case of Morvan syndrome and the first detailed review of the clinical and therapeutic literature of all 27 cases from the English language literature. Morvan syndrome is considered to be an autoimmune disorder and antibodies against voltage-gated potassium channels are found in most cases. Oral immunomodulatory therapy, intravenous immunoglobulin, and plasmapharesis may be entertained. Thymoma is found in approximately 50% of cases and thymectomy may be curative as in our particular case.

Antibodies to voltage-gated potassium channels (VGKC) are associated with acquired neuromyotonia, limbic encephalitis, and Morvan's syndrome. The antibodies are often not associated with malignancy and have shown good clinical response to immunomodulatory therapies. A record review identified five patients with laboratory evidence of antibodies to VGKC who underwent plasma exchange (PE) as part of their immunosuppressive therapy for neurologic disease. Four of the patients presented with limbic encephalitis and one with neuromyotonia. Symptoms included memory impairment, seizures, and personality changes. All PE were 1.0 volume and were performed on an every-other-day schedule. Replacement fluid was 5% normal serum albumin except when a bleeding risk was identified and then fresh frozen plasma was added. Four of five patients were also receiving concurrent immunosuppressive therapy including corticosteroids. Of the five patients treated with PE, three had sustained improvement in symptoms for 6-17 months following PE. Two patients did not have signs of improvement at a limited follow-up. One patient had recurrence of her symptoms, which responded to additional PE. These cases, as well as the reports in the literature, suggest that PE could be a useful adjunctive therapy for patients with VGKC antibodies and neurologic symptoms.

We describe a woman with both central and peripheral nervous system symptoms consistent with Morvan’s syndrome who was successfully treated with immunosuppression including rituximab and the new antiepileptic drug lacosamide against peripheral nerve hyperexcitability. Despite being over 8 months in hospital and 4 months in an intensive care unit she recovered fully. It is also the first case where cerebrospinal fluid neurofilament-light (NfL) levels were followed during the disease course. The clinical course resembled that of anti-NMDA receptor encephalitis, where patients often recover surprisingly well despite severe symptoms and an extensive time in intensive care. A possible explanation is the comparatively low levels of NfL, indicating disease processes that are not characterised by extensive neuroaxonal degeneration.

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.

Morvan's syndrome is a rare autoimmune channelopathy. A case of Morvan's syndrome is presented as a paraneoplastic syndrome associated to the recurrence of a well-differentiated thymic carcinoma, which showed a good clinical response to treatment with intravenous immunoglobulin.El síndrome de Morvan es una canalopatía rara de origen autoinmune. Se presenta el caso de un síndrome de Morvan como una entidad paraneoplásica asociada a la recurrencia de un carcinoma tímico bien diferenciado, el cual presentó una buena respuesta clínica al tratamiento con inmunoglobulina intravenosa.

Morvan’s syndrome is a rare neurological condition characterized by the combination of neuromyotonia, autonomic instability and encephalopathy, associated with auto-antibodies against voltage-gated potassium channels. We report a patient with an initial presentation suggestive of typical Guillain–Barre syndrome (GBS), who later developed clinical and laboratory features compatible with Morvan’s syndrome. Several months after resolution of the neurological symptoms, as well as disappearance of the characteristic anti-leucine-rich, glioma inactivated 1 (anti-LGI1) antibodies, the patient presented with episodes of fever of unknown origin, during which the antibodies became positive again, suggesting the possibility of a relapse. In this case, both the GBS-like symptoms at presentation and the isolated episodes of fever of unknown origin during follow-up are atypical, and may suggest the presence of an additional, yet unknown antibody.

Morvan's syndrome is a rare disorder characterized by neuromyotonia, hyperhidrosis, and central nervous system dysfunction. We report a patient with features of this syndrome, but who initially presented with breathing difficulties. Concentric needle electromyography showed an abundance of myokymic and neuromyotonic discharges. Exercise tests and repetitive nerve stimulation showed a decrement-increment response of compound muscle action potentials. Antibodies against voltage-gated potassium channels were not detected on repeated testing, but the presence of oligoclonal bands in the cerebrospinal fluid (CSF) suggested an autoimmune etiology. At follow-up over 3 years, no cancer was found. Electrophysiological in vitro studies of effects of patient serum and CSF on rat nerves provided no evidence of altered voltage-gated sodium or potassium conductances. We conclude that putative humoral factors do not block ion channels acutely but may cause channel dysfunction with chronic exposure.

To provide an overview of paraneoplastic nerve hyperexcitability syndromes.An extensive review of the literature on nerve hyperexcitability was performed. Particular attention was paid to Isaacs' syndrome and Morvan's syndrome, as well as their relationship to neoplasia.An overview of the history, clinical manifestations (including neurophysiologic findings), pathophysiology, and management is presented. Clinical differences between the exclusively peripheral nervous system involving Isaacs' syndrome and Morvan's syndrome, which also involves the central nervous system (CNS) are detailed. The role of immune-mediated dysfunction of specific components of the voltage-gated potassium channel (VGKC) complex in the pathophysiology of these syndromes is explained. Finally, the limited data on management of these syndromes, including the use of antiepileptic and immunomodulatory therapies are discussed.Nerve hyperexcitability syndrome represents a spectrum of neuroimmunologic diseases, which are often paraneoplastic in etiology.

Limbic encephalitis (LE) is often associated with lung, thymic, or testicular tumours and antibodies to Hu, CV2, or Ma2 (Ta) antigens. In these cases, it generally has a poor prognosis. Here we describe two patients with symptoms of LE, negative for typical paraneoplastic antibodies, in whom antibodies to voltage-gated potassium channels (VGKC) were detected retrospectively in serial serum samples. Patient 1 had a thymoma recurrence, but in patient 2 no tumour has been detected in the years following presentation. Plasma exchange was effective in reducing VGKC antibody levels, with substantial improvement in mental symptoms in patient 1. In patient 2, the VGKC antibodies fell spontaneously over two years, with almost complete recovery of mental function. Although neither patient had obvious neuromyotonia at presentation, both showed excessive secretions. We suggest that patients with limbic symptoms and excessive secretions should be tested for VGKC antibodies, and, if they are present, prompt and effective immunosuppressive treatment should be considered.

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.

Morvan's fibrillary chorea is a rare disease characterised by symptoms which include neuromyotonia, cramping, weakness, pruritis, hyperhidrosis, insomnia, and delirium. The first case of Morvan's fibrillary chorea to be associated with clinical manifestations of myasthenia gravis with thymoma, psoriasis, and atopic dermatitis is reported. Muscle histopathology disclosed chronic denervation and myopathic changes and in vitro electrophysiology demonstrated both presynaptic and postsynaptic defects in neuromuscular transmission. Serum antibodies to acetylcholine receptors, titin, N-type calcium channels, and voltage gated potassium channels were detected. Plasmapheresis, thymectomy, and long term immunosuppression induced a dramatic resolution of symptoms. The association of thymoma with other autoimmune disorders and autoantibodies, and prolonged and sustained remission with chronic immunosuppression, place Morvan's fibrillary chorea on the range of neurological diseases arising as a paraneoplastic complication of cortical thymomas.

We evaluated the effects of plasmapheresis in two patients with Morvan's fibrillary chorea, one of whom had sigmoid carcinoma, with oligoclonal bands in the cerebrospinal fluid, and modifications of the lipid-oxidative muscle pattern. The use of plasmapheresis in the treatment of Morvan's fibrillary chorea has not been reported previously and in our patients improved the symptoms markedly.

We describe a patient presenting with a combination of muscle fasciculations, paresthesias, hyperhidrosis, as well as insomnia, agitation and confusion. He went on to develop psychosis and respiratory failure requiring intensive care. Electromyography confirmed the presence of neuromyotonia and CSF showed mild pleocytosis. Routine testing for voltage-gated potassium channel complex (VGKC-complex) antibodies was highly positive, confirming the clinical diagnosis of Morvan's syndrome. The patient improved after treatment with intravenous immunoglobulin and methylprednisolone. Further investigation of the antigenic targets using immunohistochemistry and cell-based assays revealed that he had autoantibodies targeting Lgi1, Caspr2 and Contactin-2/Tag-1, all proteins known to be complexed with VGKC in peripheral nerves and CNS. This is the first case of Morvan's syndrome from Cyprus and illustrates the clinical features as well as the emerging complexity of antigenic targets involved in the pathogenesis.

Thymoma-associated paraneoplastic diseases include myasthenia gravis (MG), neuromyotonia (NMT), Morvan’s syndrome, and several non-neurological paraneoplastic manifestations, including glomerulonephritis. Paraneoplastic syndromes often precede the occurrence of thymoma, but cases occurring after thymomectomy, which sometimes herald the recurrence of thymoma, have also been described. We report on a patient who developed MG after thymomectomy for a malignant thymoma. After MG remission, NMT and Morvan’s syndrome occurred, which heralded a mediastinic recurrence, as demonstrated only by autopsy findings.

Morvan’s syndrome is a rare disease characterized by peripheral nerve hyperexcitability, associated with CNS and autonomic systems involvement. High serum voltage-gated potassium channel (VGKC) antibody titers have been reported, and, till now, Morvan’s syndrome has been considered as a VGKC antibody associated disease. We describe a patient with Morvan’s syndrome associated with myasthenia gravis and a thymoma in his previous history, with surprisingly undetectable levels of VGKC antibodies. The clinical course is similar to those cases of Morvan’s syndrome with VGKC-Ab, except for the lack of response to plasma exchange, previously considered as the first choice treatment. Nevertheless, the good response to corticosteroids therapy and the association with myasthenia confirm an autoimmune origin of the disease.

Pulmonary hyalinizing granulomata are rare, noninfectious, fibrosing lesions of the lung, which can mimic metastatic disease radiographically. Their etiology is unknown, but they may be caused by an exaggerated immune response. We report the radiology, long clinical course, and pathology of a patient with pulmonary hyalinizing granuloma who presented with initially asymptomatic pulmonary nodules. Over a 10-year period, the patient developed multiple insidious autoimmune phenomena, including lupus anticoagulant, neuromyotonia, demyelinating sensorimotor polyneuropathy, and eventually, Morvan's syndrome. Such an association has not been previously published to our knowledge.

Autoantibodies to Shaker -type (Kv1) K+ channels are now known to be associated with three syndromes. Peripheral nerve hyperexcitability is the chief manifestation of acquired neuromyotonia; the combination of neuromyotonia with autonomic and CNS involvement is called Morvan's syndrome (MoS); and CNS manifestations without peripheral involvement is called limbic encephalitis (LE). To determine the cellular basis of these clinical manifestations, we immunostained mouse neural tissues with sera from patients with neuromyotonia ( n = 10), MoS ( n = 2) or LE ( n = 5), comparing with specific antibodies to relevant K+ channel subunits. Fourteen of 17 patients' sera were positive for Kv1.1, Kv1.2 or Kv1.6 antibodies by immunoprecipitation of 125I-α-dendrotoxin-labelled rabbit brain K+ channels. Most sera (11 out of 17) labelled juxtaparanodes of peripheral myelinated axons, co-localizing with Kv1.1 and Kv1.2. In the CNS, all sera tested ( n = 12) co-localized with one or more areas of high Kv1.1, Kv1.2 or Kv1.6 channel expression: 10 out of 12 sera co-localized with Kv1.1 and Kv1.2 at spinal cord juxtaparanodes or cerebellar layers, while 3 out of 12 sera co-localized additionally ( n = 2) or exclusively ( n = 1) with Kv1.6 subunits in Purkinje cells, motor and hippocampal neurons. However, only sera from LE patients labelled the hippocampal areas that are enriched in excitatory, Kv1.1-positive axon terminals. All sera (17 out of 17) labelled one or more of these Kv1 subunits when expressed at the cell membrane of transfected HeLa cells, but not when they were retained in the endoplasmic reticulum. Again, LE sera labelled Kv1.1 subunits more prominently than did MoS or neuromyotonia sera, suggesting an association between higher Kv1.1 specificity and limbic manifestations. In contrast, neuromyotonia sera bound more strongly to Kv1.2 subunits than to Kv1.1 or Kv1.6. These studies support the hypothesis that antibodies to mature surface membrane-expressed Shaker -type K+ channels cause acquired neuromyotonia, MoS and LE, and suggest that future assays based on immunofluorescence of cells expressing individual Kv1 subunits will prove more sensitive than the immunoprecipitation assay. Although more than one type of antibody is often detectable in individual sera, higher affinity for certain subunits or subunit combinations may determine the range of clinical manifestations.

This study was conducted to clarify the clinical and neurophysiologic characteristics of patients with Morvan syndrome, and to compare and contrast this syndrome with other forms of autoimmune encephalitis. A retrospective chart review of the clinical features and neurophysiologic studies of two cases of Morvan syndrome seen at the Mayo Clinic was performed. Neurophysiologic studies included polysomnography, comprehensive autonomic testing, MRI, positron emission tomography, EEG, and single-photon emission computed tomography. In two cases of Morvan syndrome, the clinical features, electrophysiologic findings, and immunologic studies (high levels of voltage-gated potassium channel antibodies) were consistent with previously reported findings. Several novel observations were made. Autonomic testing demonstrated peripheral autonomic neuropathy in addition to autonomic hyperactivity. Polysomnography showed complete absence of sleep. Neuroimaging study findings were largely normal. Morvan syndrome is an autoimmune disorder affecting both the peripheral and central nervous system. Neurophysiologic studies demonstrate hyperexcitability of peripheral nerves, autonomic dysfunction, and severe insomnia. The absence of abnormalities on imaging studies suggests that central nervous system symptoms are related to functional rather than structural disruption of neural networks.

A 70 year old male presented in February 2000 with persistent cough. Chest radiograph revealed a mediastinal abnormality. A computed tomography (CT) scan of the thorax confirmed an anterior mediastinal mass. CT guided mediastinal biopsy was performed but proved inconclusive. The patient declined further invasive investigation for 2 years. After follow up CT showed significant enlargement he underwent surgery in September 2002. An excellent post operative recovery was made. Histology confirmed a minimally invasive thymoma. However, 6 weeks later he developed progressive proximal leg weakness, lethargy, and night sweats. He described a sensation like “someone touching his legs” and became agitated and restless at night. He was readmitted in November 2002 and on the first night became acutely confused and markedly disorientated with visual hallucinations. On examination he was agitated and confused. His eyes opened spontaneously, there was no coherent verbalisation, and he withdrew to pain. He was apyrexial although there was marked hyperhidrosis and hypersalivation. Blood pressure was 120/70 mm Hg, and pulse was 98 bpm and regular. He had profuse diarrhoea although his abdomen was soft and non-tender. There were irregular myoclonic jerks of all four limbs predominating in his upper limbs as elbow flexion jerks. There was no startle reaction. Cranial nerve examination was unremarkable. Power and deep tendon reflexes were normal and plantar responses flexor. Intravenous phenytoin was administered with resolution of the myoclonic movements. Laboratory investigations including electrolytes, auto-antibody screen, and anti-neuronal antibodies were unremarkable. Cerebral spinal fluid (CSF) was clear, colourless, and acellular, CSF glucose was 4.0 mmol/l …

Antibodies to voltage-gated potassium channels (VGKCs) appear likely to be the effector mechanisms in many patients with acquired peripheral nerve hyperexcitability (APNH) syndromes, a group of disorders that include neuromyotonia, cramp-fasciculation syndrome, and Isaacs' syndrome. They may contribute to the associated autonomic changes. Through a central action, they may also be the effector mechanism in those with Morvan's syndrome and in some patients with limbic encephalitis. Evidence supporting this hypothesis includes the increased association of APNH with autoimmune diseases (in particular, myasthenia gravis and thymoma), the response to plasmapheresis, passive transfer of APNH to experimental animals by patients' plasma or immunoglobulins, the action of their serum on VGKC currents studied in vitro, and the presence in many patients of IgG antibodies to VGKCs.

A previously well 66-year-old man presented with a 1-month history of focal involuntary spasms of his arms and then his left leg, culminating in two generalised convulsions. He also complained of episodic memory problems, sleeping difficulties, daytime somnolence, hyperphagia, hyperhidrosis and erectile impotence. He was initially treated with phenytoin for 2 months and then valproate. His family noticed increasing dishevelment and emotional lability over the previous 6 months. Both he and his step-daughter reported that he did not drink to excess, although 10 years previously he was a heavy drinker, but had since cut down considerably. On examination, he was flamboyant, disinhibited and garrulous, but alert and orientated. He confabulated about attending to business and family affairs, whereas he had not worked for several years. He was able to learn a name and address perfectly in three attempts. He showed difficulties in naming people, word-finding and planning constructional tasks, which is indicative of fronto-temporal impairment. Cranial nerves were normal with no frontal release signs. There were prominent fasciculations bilaterally in quadriceps femorii, gastrocnemii and right biceps femoris. Power and coordination were normal. Deep tendon reflexes were absent except for biceps jerks. Plantar responses were flexor. Sensation was intact. The following blood tests …

Acquired neuromyotonia is characterized by hyperexcitability of motor nerves leading to muscle twitching, cramps, and weakness. The symptoms may improve following plasma exchange, and injection of immunoglobulin G (IgG) from 1 neuromyotonia patient into mice increased the resistance of neuromuscular transmission to d-tubocurarine. Here we examine nerves and muscle in vitro from mice injected with plasma or purified IgG from 6 neuromyotonia patients or pooled control subjects, and cultured dorsal root ganglion cells after treatment with IgG. Three of the patients had antibodies against human voltage-gated potassium channels labeled with 125I-alpha-dendrotoxin. The quantal release of acetylcholine (quantal content) at end-plates in diaphragms from mice treated with neuromyotonia IgG preparations was increased by 21% relative to control values (p = 0.0053). With one IgG preparation, the duration of the superficial peroneal nerve compound action currents was increased by 93%. The dorsal root ganglion cells treated with this IgG showed a marked increase in repetitive firing of action potentials. All effects were similar to those obtained with aminopyridines. We conclude that at least some patients with acquired neuromyotonia have antibodies directed against aminopyridine- or alpha-dendrotoxin-sensitive K+ channels in motor and sensory neurons, and they are likely to be implicated in the disease process.

The French physician Augustine Marie Morvan first used the term 'la choriotae fibrillare' to describe a syndrome characterized by peripheral nerve hyperexcitability, dysautonomia, insomnia and fluctuating delirium. There are no published reports of the condition from the Indian subcontinent. We report the first such case from the region. Our patient, a 24-year-old male, presented with easy fatigability and stiffness in both the calves for 18 months; continuous twitching of muscles of all four limbs and jaw for two months; hyperhydrosis, palpitations, urinary symptoms, burning dysesthesia in hands, insomnia and abnormal sleep behavior for about a month. Patient had bilateral hyper-reflexia with extensor plantar on the right and equivocal response on the left. Electromyography revealed continuous muscle fiber activity. Thyroid function test, electroencephalography, computerized tomography scan (head) and routine cerebrospinal fluid analysis were normal. The patient showed marked clinical and electrophysiological improvement on prednisolone along with symptomatic therapy over the next two months.

Neuromyotonia, or Isaacs’ syndrome, is a syndrome of continuous muscle fiber activity caused by hyperexcitability of peripheral nerves.1 Patients present with myokymia, muscle stiffness, cramps, impaired muscle relaxation, and hyperhidrosis. Rarely, these patients also develop an encephalopathy characterized by confusion, insomnia, hallucinations, and agitation.1-5 Neuroimaging results and CSF are usually normal. The EEG typically shows generalized slowing. The triad of neuromyotonia, hyperhidrosis, and encephalopathy is called Morvan’s syndrome. A 62-year-old man presented with a 6-week history of insomnia, malaise, anorexia, hyperhidrosis, and burning pain in both feet. He developed an unsteady gait, drowsiness, fluctuating confusion, generalized headache, and vomiting 3 days before presentation. Five months earlier he was treated for legionella pneumonia. He had presented 15 years earlier with an acute confusional state and vomiting. The cause of these earlier symptoms was not found, but he recovered fully. He was afebrile and there was no meningismus. He was drowsy and intermittently confused. His …