Clinical features of neuromuscular disorders in patients with N-type voltage-gated calcium channel antibodies

Abstract

Neuromuscular junction disorders affect the pre- or postsynaptic nerve to muscle transmission due to autoimmune antibodies. Members of the group like myasthenia gravis and Lambert-Eaton syndrome have pathophysiologically distinct characteristics. However, in practice, distinction may be difficult. We present a series of three patients with a myasthenic syndrome, dropped-head syndrome, bulbar and respiratory muscle weakness and positive testing for anti-N-type voltage-gated calcium channel antibodies. In two cases anti-acetylcholin receptor antibodies were elevated, anti-P/Q-type voltage-gated calcium channel antibodies were negative. All patients initially responded to pyridostigmine with a non-response in the course of the disease. While one patient recovered well after treatment with intravenous immunoglobulins, 3,4-diaminopyridine, steroids and later on immunosuppression with mycophenolate mofetil, a second died after restriction of treatment due to unfavorable cancer diagnosis, the third patient declined treatment. Although new antibodies causing neuromuscular disorders were discovered, clinical distinction has not yet been made. Our patients showed features of pre- and postsynaptic myasthenic syndrome as well as severe dropped-head syndrome and bulbar and axial muscle weakness, but only anti-N-type voltage-gated calcium channel antibodies were positive. When administered, one patient benefited from 3,4-diaminopyridine. We suggest that this overlap-syndrome should be considered especially in patients with assumed seronegative myasthenia gravis and lack of improvement under standard therapy.

Disruption of Neuromuscular Junction Following Spinal Cord Injury and Motor Neuron Diseases

“…Autoimmune antibodies directed against the voltage-gated calcium channels in the presynaptic membranes of motor nerve terminals cause reduced neuromuscular transmission [ 78 ], resulting in characteristic muscle weakness in patients with LEMS. These channels play a key role in transmitting signals between nerves and muscles, and their dysfunction or destruction can lead to clinical symptoms [ 67 , 79 ].…”

“…weakness in patients with LEMS. These channels play a key role in transmitting signals between nerves and muscles, and their dysfunction or destruction can lead to clinical symptoms [67,79].…”

Neuromuscular Causes of Weakness in Critically Ill Patients

“…22 Botulism and tick paralysis are amongst the uncommon neuromuscular junction disorders encountered in an ICU. Botulism presents with flaccid paralysis, areflexia, and autonomic disturbances.…”