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Morvan just a syndrome…!
Case Report
seizures, CASPR2 antibodies are associated with peripheral nerve hyperexcitability and encephalitis. Up to 40% of cases have been associated with thymoma,1,2,5 which can also produce antibodies that cause other paraneoplastic syndromes, such as Lambert-Eaton myasthenic syndrome, paraneoplastic cerebellar degeneration, or stiff person syndrome. Immunotherapy—corticosteroids, immunoglobulins, plasmapheresis, azathioprine, or cyclo phosphamide2— can be used in the treatment of paraneoplastic autoimmine encephalopathies, and low doses of carbamazepine or phenytoin can often give relief of neuromyotonia.1–3 Contributors JLP, TCV, LAD, LA, and OGB cared for the patient. LHPF, LBFP, and GFP did the EMG, EEG, and polysomnogram. RH analysed the serum
and CSF samples. All authors contributed to writing of the report. Written consent to publication was obtained. References 1 Höftberger R, Rosenfeld MR, Dalmau J. Update on neurological paraneoplastic syndromes. Curr Opin Oncol 2015; 27: 489–95. 2 Irani SR, Pettingill P, Kleopas A, et al. Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol 2012; 72: 241–55. 3 Lee EK, Maselli RA, Ellis WG, Agius MA. Morvan’s fibrillary chorea: a paraneoplastic manifestation of thymoma. J Neurol Neurosurg Psychiatry 1998; 65: 857–62. 4 Abgrall G, Demeret S, Rohaut B, Leu-Semenescu S, Arnulf I. Status dissociatus and disturbed dreaming in a patient with Morvan syndrome plus myasthenia gravis. Sleep Med 2015; 16: 894–96. 5 Olsen AL, Lai Y, Dalmau J, Scherer SS, Lancaster E. Caspr2 autoantibodies target multiple epitopes. Neurol Neuroimmunol Neuroinflamm 2015; 2: e127.
Case Report Comment Morvan just a syndrome...! Ernest R Somerville, Arjune Sen Lancet 2017; 389: 1368 Comprehensive Epilepsy Service, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia (Prof E R Somerville FRCP); and Oxford Epilepsy Research Group, National Institute of Health Research, Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK (Prof A Sen FRCP) Correspondence to: Prof Ernest R Somerville, Comprehensive Epilepsy Service, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2031, Australia [email protected]
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Neurologists are often perceived as diagnosticians with little in the way of treatments to benefit their patients. However, this view is being gradually dispelled. In no area of neurology is this occurring more rapidly than in neuroimmunology, where recognition of constellations of clinical signs can lead to prompt and effective treatment, often preventing serious sequelae. In The Lancet, Thiago Vale and colleagues1 describe a man who illustrates the many curious features of Morvan syndrome, a rare male-predominant autoimmune disorder characterised by peripheral nerve hyperexcitability, auto nomic dysfunction, and encephalopathy, often with severe insomnia accompanied by dream enactment and hallucinations (agrypnia excitata).2,3 Peripheral nerve hyperexcitability manifests as fasciculations and con tinuous low amplitude muscle fibre contractions, resulting in a “bag of worms” appearance known as myokymia and well illustrated in the video accompanying Vale’s case report. Electromyography shows spontaneous motor unit action potentials firing as doublets or triplets. Most patients have CASPR2 antibodies in their serum. Morvan syndrome is just one of the ever-broadening spectrum of autoimmune neurological disorders, which now encompasses seizures, memory loss, behavioural disorders, cerebellar degeneration, movement disorders, myelopathy, peripheral neuropathy, myasthenia gravis, and myositis. In many patients the disorder is paraneoplastic, but the same syndromes can occur in the absence of a detectable tumour. An intriguing aspect of autoimmune neurological syndromes is that the same antibody can cause quite different syndromes in different patients. AntiHu antibodies, for example, are associated with limbic encephalitis in some patients and sensory neuropathy in others.4 Conversely, the same syndrome can be associated with different antibodies—eg, LGI1 antibodies might be
associated with a distinctive seizure type5 but have also been found in some patients with Morvan syndrome.2,3 Some patients have more than one autoantibody, suggesting a more widespread derangement of their immune system. In the largest reported series of patients with Morvan syndrome, more patients had both LGI1 and CASPR2 antibodies than had either antibody alone.3 Although rare, the clinical importance of early recognition of Morvan syndrome and other autoimmune neurological syndromes lies in their responsiveness to immunomodulatory therapy. Antibody testing can take time, but in some cases the clinical features might allow a confident diagnosis and initiation of therapy while awaiting confirmation of a positive antibody titre. Moreover, some neurological autoimmune disorders are associated with tumours that are resectable; up to half of patients with Morvan syndrome harbour thymomas, as the patient in this case did. Removal of the tumour might cure the autoimmune disorder. As the number of detectable antibodies continues to expand and the spectrum of clinical symptoms and signs associated with each antibody increases, physicians must maintain their clinical skills to enable recognition of these disorders at the bedside. References 1 Vale TG, Pedroso JL, Dutra LA, et al. Morvan syndrome as a paraneoplastic disorder of a thymoma with anti-CASPR-2 antibodies. Lancet 2017; 389: 1367–68. 2 Irani SR, Pettingill P, Kleopas A, et al. Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol 2012; 72: 241–55. 3 van Sonderen A, Ariño H, Petit-Pedrol M, et al. The clinical spectrum of Caspr2 antibody-associated disease. Neurology 2016; 87: 521–28. 4 Höftberger R, Rosenfeld MR, Dalmau J. Update on neurological paraneoplastic syndromes. Curr Opin Oncol 2015; 27: 489–95. 5 Sen A, Wang J, Laue-Gizzi H, Lee T, Ghougassian D, Somerville ER. Pathognomonic seizures in limbic encephalitis associated with anti-LGI1 antibodies. Lancet 2014; 383: 2018. www.thelancet.com Vol 389 April 1, 2017
seizures, CASPR2 antibodies are associated with peripheral nerve hyperexcitability and encephalitis. Up to 40% of cases have been associated with thymoma,1,2,5 which can also produce antibodies that cause other paraneoplastic syndromes, such as Lambert-Eaton myasthenic syndrome, paraneoplastic cerebellar degeneration, or stiff person syndrome. Immunotherapy—corticosteroids, immunoglobulins, plasmapheresis, azathioprine, or cyclo phosphamide2— can be used in the treatment of paraneoplastic autoimmine encephalopathies, and low doses of carbamazepine or phenytoin can often give relief of neuromyotonia.1–3 Contributors JLP, TCV, LAD, LA, and OGB cared for the patient. LHPF, LBFP, and GFP did the EMG, EEG, and polysomnogram. RH analysed the serum
and CSF samples. All authors contributed to writing of the report. Written consent to publication was obtained. References 1 Höftberger R, Rosenfeld MR, Dalmau J. Update on neurological paraneoplastic syndromes. Curr Opin Oncol 2015; 27: 489–95. 2 Irani SR, Pettingill P, Kleopas A, et al. Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol 2012; 72: 241–55. 3 Lee EK, Maselli RA, Ellis WG, Agius MA. Morvan’s fibrillary chorea: a paraneoplastic manifestation of thymoma. J Neurol Neurosurg Psychiatry 1998; 65: 857–62. 4 Abgrall G, Demeret S, Rohaut B, Leu-Semenescu S, Arnulf I. Status dissociatus and disturbed dreaming in a patient with Morvan syndrome plus myasthenia gravis. Sleep Med 2015; 16: 894–96. 5 Olsen AL, Lai Y, Dalmau J, Scherer SS, Lancaster E. Caspr2 autoantibodies target multiple epitopes. Neurol Neuroimmunol Neuroinflamm 2015; 2: e127.
Case Report Comment Morvan just a syndrome...! Ernest R Somerville, Arjune Sen Lancet 2017; 389: 1368 Comprehensive Epilepsy Service, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia (Prof E R Somerville FRCP); and Oxford Epilepsy Research Group, National Institute of Health Research, Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK (Prof A Sen FRCP) Correspondence to: Prof Ernest R Somerville, Comprehensive Epilepsy Service, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2031, Australia [email protected]
1368
Neurologists are often perceived as diagnosticians with little in the way of treatments to benefit their patients. However, this view is being gradually dispelled. In no area of neurology is this occurring more rapidly than in neuroimmunology, where recognition of constellations of clinical signs can lead to prompt and effective treatment, often preventing serious sequelae. In The Lancet, Thiago Vale and colleagues1 describe a man who illustrates the many curious features of Morvan syndrome, a rare male-predominant autoimmune disorder characterised by peripheral nerve hyperexcitability, auto nomic dysfunction, and encephalopathy, often with severe insomnia accompanied by dream enactment and hallucinations (agrypnia excitata).2,3 Peripheral nerve hyperexcitability manifests as fasciculations and con tinuous low amplitude muscle fibre contractions, resulting in a “bag of worms” appearance known as myokymia and well illustrated in the video accompanying Vale’s case report. Electromyography shows spontaneous motor unit action potentials firing as doublets or triplets. Most patients have CASPR2 antibodies in their serum. Morvan syndrome is just one of the ever-broadening spectrum of autoimmune neurological disorders, which now encompasses seizures, memory loss, behavioural disorders, cerebellar degeneration, movement disorders, myelopathy, peripheral neuropathy, myasthenia gravis, and myositis. In many patients the disorder is paraneoplastic, but the same syndromes can occur in the absence of a detectable tumour. An intriguing aspect of autoimmune neurological syndromes is that the same antibody can cause quite different syndromes in different patients. AntiHu antibodies, for example, are associated with limbic encephalitis in some patients and sensory neuropathy in others.4 Conversely, the same syndrome can be associated with different antibodies—eg, LGI1 antibodies might be
associated with a distinctive seizure type5 but have also been found in some patients with Morvan syndrome.2,3 Some patients have more than one autoantibody, suggesting a more widespread derangement of their immune system. In the largest reported series of patients with Morvan syndrome, more patients had both LGI1 and CASPR2 antibodies than had either antibody alone.3 Although rare, the clinical importance of early recognition of Morvan syndrome and other autoimmune neurological syndromes lies in their responsiveness to immunomodulatory therapy. Antibody testing can take time, but in some cases the clinical features might allow a confident diagnosis and initiation of therapy while awaiting confirmation of a positive antibody titre. Moreover, some neurological autoimmune disorders are associated with tumours that are resectable; up to half of patients with Morvan syndrome harbour thymomas, as the patient in this case did. Removal of the tumour might cure the autoimmune disorder. As the number of detectable antibodies continues to expand and the spectrum of clinical symptoms and signs associated with each antibody increases, physicians must maintain their clinical skills to enable recognition of these disorders at the bedside. References 1 Vale TG, Pedroso JL, Dutra LA, et al. Morvan syndrome as a paraneoplastic disorder of a thymoma with anti-CASPR-2 antibodies. Lancet 2017; 389: 1367–68. 2 Irani SR, Pettingill P, Kleopas A, et al. Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol 2012; 72: 241–55. 3 van Sonderen A, Ariño H, Petit-Pedrol M, et al. The clinical spectrum of Caspr2 antibody-associated disease. Neurology 2016; 87: 521–28. 4 Höftberger R, Rosenfeld MR, Dalmau J. Update on neurological paraneoplastic syndromes. Curr Opin Oncol 2015; 27: 489–95. 5 Sen A, Wang J, Laue-Gizzi H, Lee T, Ghougassian D, Somerville ER. Pathognomonic seizures in limbic encephalitis associated with anti-LGI1 antibodies. Lancet 2014; 383: 2018. www.thelancet.com Vol 389 April 1, 2017