Conjoint occurrence of GABA-B receptor antibodies in Lambert-Eaton myasthenic syndrome with antibodies to the voltage gated calcium channel M¨ujgan Dogan Onugoren, Helmut Rauschka, Christian G. Bien PII: DOI: Reference:

S0165-5728(14)00153-2 doi: 10.1016/j.jneuroim.2014.05.011 JNI 475915

To appear in:

Journal of Neuroimmunology

Received date: Revised date: Accepted date:

28 January 2014 17 May 2014 20 May 2014

Please cite this article as: Onugoren, M¨ ujgan Dogan, Rauschka, Helmut, Bien, Christian G., Conjoint occurrence of GABA-B receptor antibodies in Lambert-Eaton myasthenic syndrome with antibodies to the voltage gated calcium channel, Journal of Neuroimmunology (2014), doi: 10.1016/j.jneuroim.2014.05.011

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ACCEPTED MANUSCRIPT Conjoint occurrence of GABA-B receptor antibodies in Lambert-Eaton myasthenic

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Müjgan Dogan Onugoren1 –Helmut Rauschka2 - Christian G Bien1

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syndrome with antibodies to the voltage gated calcium channel

Epilepsy Centre Bethel, Krankenhaus Mara, Bielefeld, Germany; 2 Department of

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Neurology, Sozialmedizinisches Zentrum Ost – Donauspital, Vienna, Austria

Keywords:

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Lambert-Eaton myasthenic syndrome – paraneoplastic antibodies - GABAB receptor

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antibodies – voltage gated calcium channel antibodies

Dr. M. Dogan Onugoren

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Epilepsy Centre Bethel Krankenhaus Mara Maraweg 17-21

33617 Bielefeld Germany [email protected] Telephone: +49-521-77278908 Fax: +49-521-77278857

ACCEPTED MANUSCRIPT Abstract Antibodies (abs) to the GABAB receptor have been recently found to be responsible for

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immune-mediated encephalitis with dominant seizures. They are in approximately 50% of

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cases associated with small-cell lung cancer (SCLC). GABAB receptors are mainly located in

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the hippocampus, thalamus and cerebellum in the presynaptic and postsynaptic regions of synapses. The main function of these receptors is to reduce activity states of neurons. In some instances, GABAB receptor abs in these patients were accompanied by other antibodies,

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among them VGCC abs (Lancaster et al., 2010, Boronat et al., 2011). VGCC abs cause

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paraneoplastic Lambert Eaton myasthenic syndrome (LEMS) by reduction of presynaptic VGCCs (Titulaer et al., 2011). In the domain of CNS disease, VGCC abs have been found in association with paraneoplastic cerebellar ataxia (Mason et al., 1997) and rarely and at low

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titres also in other paraneoplastic encephalopathies together with Hu abs (Lennon et al., 1995). It has been a long-standing debate if abs in paraneoplastic conditions associate rather

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with the neurological syndrome or the tumour. Here, we describe the conjoint occurrence of abs to the GABAB receptor and to the VGCC in

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a patient with SCLC presenting only symptoms of the peripheral nervous system giving another example of the latter hypothesis. Case description

A 47-year-old woman with a long history of nicotine abuse was admitted to the neurological department due to progressive weakness in the legs over the last 4 weeks, blurred vision, diplopia and dyspnoea on mild exertion. Neurological examination revealed cranial nerve disorders including diplopia and right-sided soft palate paresis as well as decreased tendon reflexes. Cranial CT as well as MRI showed no abnormalities. Electrophysiological studies disclosed significant presynaptic disturbances in the neuromuscular transmission. Using repetitive nerve stimulation at low frequencies (3Hz) of both nervi accessorii, a significant decrement of 10%

ACCEPTED MANUSCRIPT or 13% respectively was detected. Post-exercise stimulation of both ulnar nerves revealed significant increase (370%) of compound muscle action potential (CMAP), which was

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considered diagnostic of LEMS. In line with these findings, abs to P/Q-type VGCC were

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elevated (543 pmol/l; normal range

Conjoint occurrence of GABAB receptor antibodies in Lambert-Eaton myasthenic syndrome with antibodies to the voltage gated calcium channel.

Antibodies (abs) to the GABAB receptor have been recently found to be responsible for immune-mediated encephalitis with dominant seizures. They are in...
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