Isaacs syndrome: A review

Abstract

Isaacs syndrome is a peripheral nerve hyperexcitability (PNH) syndrome that presents as continuous motor activity. Clinical findings include cramps, fasciculations, and myokymia. Electrodiagnosis plays a key role in diagnosis by demonstrating after-discharges on nerve conduction studies, and fasciculation potentials, myokymic discharges, neuromyotonic discharges, and other types of abnormal spontaneous activity on needle examination. Etiopathogenesis involves the interaction of genetic, autoimmune, and paraneoplastic factors, which requires a broad-ranging evaluation for underlying causes. Initial treatment is symptomatic, but immune therapy is often needed and can be effective. The purpose of this review is to describe the syndrome and its pathogenesis, assist the reader in evaluating patients with suspected Isaacs syndrome and distinguishing it from other disorders of PNH, and suggest an approach to management, including both symptomatic and immunomodulating therapy.

Antiepileptic drug therapy in patients with autoimmune epilepsy

“…12 These agents act by reducing neuronal repetitive firing through interaction with voltage-gated sodium channels. 11,12 Perhaps, the observed favorable response of these agents in VGKC-complex ab–associated AE is attributable to this mechanism. In our series, one patient with GAD65 ab–associated AE became seizure free with carbamazepine after failing immunotherapy.…”

“…Two of these responded to oxcarbazepine, one to lacosamide, and the other to carbamazepine (figure 1). Indeed, sodium-channel blocking agents such as carbamazepine and phenytoin have been successfully used to treat autoimmune VGK channelopathies such as neuromyotonia 11 and episodic ataxia type 1. 12 These agents act by reducing neuronal repetitive firing through interaction with voltage-gated sodium channels.…”

Focal neurogenic muscle hypertrophy and fasciculations in multifocal motor neuropathy

“…Immunoglobulin M (IgM) antibodies to the ganglioside GM1 were negative in our patient, but only half of MMN patients have such antibodies . There was no clinical, electrophysiologic, or biologic evidence of Isaacs syndrome …”

Antiepileptic drug therapy in autoimmune epilepsy associated with antibodies targeting the leucine‐rich glioma‐inactivated protein 1

“…13 Carbamazepine has also been shown to inhibit the development of inflammation via dose-dependent reduction of prostaglandin E2 and substance P. 14,15 NCB AEDs, including carbamazepine, have been noted to be efficacious in other VGKC channelopathies such as immune-mediated neuromyotonia and hereditary episodic ataxia type 1. 16,17 Although these agents act primarily by either slow or fast inactivation of voltagegated sodium channels, at concentrations used to treat epilepsy, some of these have also been shown to modulate ATP-sensitive potassium channels as well as calcium-activated potassium channel activity. 18,19 Alternatively, the potential class effect with NCBs could be due to a delayed therapeutic response to immunotherapy instituted prior to or during the NCB-AED use.…”