Cross-syndrome: myasthenia gravis and the demyelinating diseases of the central nervous system combination. Systematic literature review and case reports

Acta Neurol Belg. 2023 Apr;123(2):367-374. doi: 10.1007/s13760-022-01926-z. Epub 2022 Jun 14.


Nowadays the problem of comorbidity is still relevant. In this review, we describe clinical cases of the disease of the neuromuscular junction (myasthenia gravis (MG) generalized form) and the demyelinating disease of the central nervous system (DD CNS) (multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), etc.) combinations registered in our practice with precise pathogenetic analysis. Although the number of the described associations is growing every year, the exact development mechanisms of this cross syndrome as well as the nature of the association between the discussed autoimmune diseases remain unknown. At the beginning of both disorders there is a considerable loss of auto tolerance of the immune system and, as a result, an increased response from autoreactive T-lymphocytes to the structures of the nervous system: brain cells and neuromuscular synapses. There are three main theories for comorbidity: initial predisposition, direct case relationship with disease-modifying therapy (DMT) application, and coincidence. It is known that early diagnostics of MG and timely administration of necessary adequate treatment reduce the risk of process generalization and lead to a decline in mortality. Therefore, the offer to examine MS patients with atypical symptoms for possible MG identification seems very rational. Similarly, MG patients having uncharacteristic symptoms that can be indicative of other autoimmune nervous system diseases also demand special diagnostics. Considering the presence of similar pathogenetic links, several authors propose a possibility of a new nosological unit establishment, including described comorbidity.

Publication types

  • Systematic Review
  • Case Reports
  • Review

MeSH terms

  • Central Nervous System
  • Humans
  • Multiple Sclerosis* / complications
  • Myasthenia Gravis* / complications
  • Neuromyelitis Optica* / complications
  • Pigmentation Disorders* / complications

Supplementary concepts

  • Oculocerebral hypopigmentation syndrome type Preus