Recently, a good friend suffered two puzzling episodes of prolonged weakness. Despite two hospitalizations and evaluations by his primary physician, a neurologist, and a rheumatologist the etiology remains undetermined.
His neurologist has drawn some blood tests for possible myasthenia gravis. My friend asked me to review myasthenia gravis and discuss it and tests for the disease with him.
Reference (1) is an excellent brief review and update of myasthenia gravis:
Myasthenia gravis (MG) is the archetypic disorder
of both the neuromuscular junction and autoantibodymediated
disease. In most patients, IgG1-dominant antibodies
to acetylcholine receptors cause fatigable weakness
of skeletal muscles. In the rest, a variable proportion possesses
antibodies to muscle-specific tyrosine kinase while
the remainder of seronegative MG is being explained
through cell-based assays using a receptor-clustering technique
and, to a lesser extent, proposed new antigenic targets.
The incidence and prevalence of MG are increasing, particularly
in the elderly.The co-occurrence of MG and demyelinating disorders
happens more than would be expected by chance [76].
Recently, a cohort of 16 patients with neuromyelitis optica
(NMO) and MG was described. In such cases, the MG tended
to be mild and 90 % presented with a prior history of NMO;
however, Aquaporin-4 (AQP4) antibodies could pre-date
clinically evident NMO by up to 16 years [76]. Of note, in
other case series of MG presenting with demyelinating disorders
described as MS or ADEM, AQP4 testing was not
reported; some of these may have represented NMO [77–79]
and in at least one case this was subsequently confirmed [78].
LRP4 antibodies have also been described in NMO patients,
albeit without a known diagnosis of MG, but not other neurological
disorders [70]. Why these two diseases should
occur in this order, with AQP4 antibodies rising over time, is
not understood, although it is speculated that thymectomy
may play a triggering role. Clinicians should at least be
vigilant to the possible co-existence of NMO with MG,
particularly in young patients with AChR-antibody-positive
disease and should test for AQP4 antibodies in MG patients
who develop MS or other demyelinating disorders [76].
Resources:
(1) Myasthenia gravis: a clinical-immunological update. [PubMed Abstract] [Full Text HTML] [Full Text PDF]. J Neurol. 2016 Apr;263(4):826-34. doi: 10.1007/s00415-015-7963-5. Epub 2015 Dec 24.
(2) Myasthenia Gravis Overview from Medscape (accessed 5-4-2016).
(3) Myasthenia in pregnancy: best practice guidelines from a UK multispecialty working group. [PubMed] [Cross Ref]. J Neurol Neurosurg Psychiatry. 2014;85(5):538–543. doi: 10.1136/jnnp-2013-305572.
(4) EFNS/ENS Guidelines for the treatment of ocular myasthenia. [PubMed] [Cross Ref]Eur J Neurol. 2014;21(5):687–693. doi: 10.1111/ene.12359.
(5) Myasthenia gravis: association of British Neurologists’ management guidelines. [PubMed] [Full Text HTML] [Full Text PDF] Pract Neurol. 2015;15(3):199–206. doi: 10.1136/practneurol-2015-001126.
