A Chinese female Morvan patient with LGI1 and CASPR2 antibodies: a case report

Abstract

BackgroundMorvan syndrome is a rare disorder characterized by the combination of peripheral nerve hyperexcitability, encephalopathy and dysautonomia with marked insomnia. It was reported to have association to antibodies to voltage-gated potassium channels including contactin associated protein-like 2 antibodies (CASPR2-Ab) and leucine-rich glioma inactivated protein 1 antibodies (LGI1-Ab). LGI1-Ab was reported to associate with seizures, amnesia, confusion, hyponatraemia and a good prognosis, while CASPR2-Ab with peripheral presentations, probable risk for tumor and a poor prognosis. The vast majority of Morvan syndrome patients were male, with normal magnetic resonance imaging of the brain.Case presentationWe report a female case presenting with a combination of bilateral leg pain, widespread myokymia, memory disturbance, seizure, hyperhidrosis and insomnia. She had antibodies targeting CASPR2 and LGI1, tested by the indirect immunofluorescence test, which demonstrated the diagnosis of typical Morvan syndrome as well as classical limbic encephalitis. Cranial MRI revealed bilateral hyper-intensity of the medial temporal lobe, insular lobe and basal ganglia on T2/FLAIR and DWI sequence. As the treatment carried on, her serum LGI1-Ab disappeared and her memory loss, seizure and confusion quickly relieved. But her peripheral presentations did not relieve until serum CASPR2-Ab turned negative. Intravenous immunoglobulin treatment showed limited efficacy while she achieved almost complete remission with corticosteroids therapy.ConclusionsThis case provides a rare female resource of Morvan syndrome, which is the first patient with both CASPR2-Ab and LGI1-Ab positive Morvan syndrome in China and one of the few female patients with Morvan syndrome reported so far. Through the detailed analysis of her clinical course, the diverse and overlapping clinical phenotype of CASPR2-Ab and LGI1-Ab in patients with Morvan syndrome was obvious and interesting.

Peripheral nerve hyperexcitability syndrome: A clinical, electrophysiological, and immunological study

“…12 However, patients with relatively mild clinical symptoms exhibit lower frequencies and discontinuous discharge modes and can thus even show normal EMG results. 13 Afterdischarges are continuous discharges after stimulation of action potentials and can promote hyperactivity of motor nerve membranes, thus serving as sensitive markers when hyperexcitability levels are low. Additionally, we found that after-discharges are more common in the tibial nerve, which is consistent with a previous study.…”

Mapping autoantigen epitopes: molecular insights into autoantibody-associated disorders of the nervous system

“…Petit-Pedrol et al (2014) recently reported five cases of anti-GABA A R and anti-GAD65 antibodies co-occurring in CSF and serum [ 17 ], and a single case report of a female with encephalitis was found to harbor anti-GABA A R and anti-GAD65 antibodies in CSF and serum [ 184 ]. Other double antibody positivity combinations that have been identified are anti-NMDAR and anti-GAD antibodies [ 185 ], anti-NMDAR and anti-D2R [ 165 , 186 ], anti-GABA B R and anti-Hu [ 187 ], and anti-Caspr2 and anti-Lgi1 in a patient with Morvan syndrome [ 188 ]. Recently, patients positive for anti-MOG and anti-NMDAR antibodies were reported [ 189 ], and later on, double antibody positivity for anti-NMDAR and anti-GlyR and anti-MOG and anti-GlyR antibodies were also shown in two patients [ 190 ].…”

Insomnia and Dysautonomia with Contactin-Associated Protein 2 and Leucine-Rich Glioma Inactivated Protein 1 Antibodies: A “Forme Fruste” of Morvan Syndrome?

“…The mechanism(s) by which CASPR2 and LGI1 antibody cause insomnia remain(s) unclear, though it was suggested that these proteins, located mainly in the neocortex and limbic areas, may be involved in the regulation of sleep need or efficiency via modulation of potassium channels. Only few reports have highlighted the reversal of insomnia in autoimmune encephalitis upon immune-modulatory therapy [4, 9, 10], as in the present case. Our patient demonstrated a major benefit from immune-modulatory therapy in terms of insomnia, as demonstrated by both clinical and polysomnographic evaluations.…”

“…Similarly, a few MoS cases with both LGI1 and CASPR2 antibodies and an incomplete clinical picture have been previously reported. However, these patients have displayed either severe PNH features (e.g., cramps, fasciculations, neuromyotonic discharges) without encephalopathy or prominent encephalopathy features (e.g., hallucination, confusion, amnesia, or seizures) with mild (e.g., myokymia only) or no PNH findings [4, 5, 6], while our patient showed minimal features of both PNH and encephalopathy findings.…”

“…Clinical studies conducted with double-positive MoS patients provide a good opportunity to study the discrepant effects of different voltage-gated potassium channel complex antibodies. LGI1 antibody has been associated with cognitive dysfunction, while CASPR2 antibody has been suggested to be related with PNH findings, dysautonomia, and diencephalon involvement [1, 4]. Presence of mild PNH and cognitive symptoms in some MoS cases with LGI1 and CASPR2 antibodies might putatively be due to a lack of antibodies reactive with pathogenic epitopes or inability of LGI1 antibodies to cross the blood-brain barrier.…”