Page 837 - Clinical Small Animal Internal Medicine

74 Diseases of the Neuromuscular Junction 805

nerve conduction studies are normal in MG. Repetitive acquired MG (see later). Regurgitation associated with
VetBooks.ir nerve stimulation may show a decremental response of megaesophagus has been reported in congenital MG but
not as commonly as in acquired MG. As expected based
the compound muscle action potential but does lack
sensitivity and specificity. More than one muscle group
would be negative. A positive edrophonium (Tensilon)
should be tested, especially in patients with focal MG. on the pathology, serologic tests for AChR antibodies
Single‐fiber EMG (SFEMG) is a sensitive test of neuro- response test (0.1–0.2 mg/kg IV) can be consistent with
muscular transmission and techniques for recording the diagnosis of congenital MG but does not allow for
SFEMG have been described in both the cat and the dog. differentiation of the acquired form of the disease and a
SFEMG records the variability of consecutive discharges negative test does not exclude the diagnosis of congenital
of the interpotential interval between two muscle MG. Other neuromuscular disorders may be excluded by
fiber action potentials belonging to the same motor routine serologic and electrophysiologic testing and
unit (jitter). In MG, the jitter values are increased. muscle and nerve biopsy. Fresh‐frozen muscle biopsy
SFEMG is technically difficult to perform and not widely samples may also be evaluated for localization of AChE,
available. All these electrodiagnostic tests need to be AChR, AChR subunits, IgG, and complement components
performed under general anesthesia so may not be at the neuromuscular junction. Quantification of muscle
suitable for all cases of neuromuscular weakness based AChR may be done but requires a fresh muscle specimen
on their anesthetic risk assessment. intact from origin to insertion, such as external intercos-
The gold standard for the diagnosis of MG is the tal or anconeus muscle.
demonstration of serum autoantibodies directed against Anticholinesterase drugs should be of benefit in ani-
muscle AChRs. The test is extremely sensitive and mals with AChR deficiency. Congenital cases of MG do
specific but cannot predict the degree of weakness or not seem to respond as completely as the acquired dis-
severity of the disease. Immunosuppressive drugs may ease with full return of strength being unusual. The
lower the antibody titers and serum should ideally be weakness can often progress to death within the first
submitted before the use of corticosteroids or other year but with proper care and anticholinesterase therapy,
immunosuppressive drugs. An AChR antibody titer of some affected Jack Russell terriers have survived several
greater than 0.6 nmol/L in the dog and 0.3 nmol/L in the years. Both cats reported with congenital MG survived
cat is diagnostic for MG, with rare false‐positive results. several years.
Seronegative MG occurs in approximately 2% of dogs
with generalized MG but the incidence of seronegative Seronegative Myasthenia Gravis
focal MG is unknown. The AChR assay is species specific
and while there is cross‐reactivity, canine or feline assay Seronegative MG does occur and the patients may have
systems should be used. Low‐positive titers may be the same clinical presentation as a seropositive case.
missed if a human AChR is used as an antigen. Seronegative MG in dogs is defined as a patient with
clinical signs suggestive of MG, a positive edrophonium
response, supportive electrodiagnostic testing (decremen-
Congenital Myasthenia Gravis
tal response on repetitive nerve stimulation, increased
Congenital MG is characterized as a postsynaptic defi- jitter on SFEMG), improvement of muscle weakness after
ciency of ACh receptors with no evidence of autoimmune anticholinesterase therapy, and at least two negative serum
destruction, with a congenital familial form (autosomal AChR antibody titers. The antibody titers should be
recessive trait) having been described in Jack Russell terri- repeated 1–2 months apart as seroconversion may occur.
ers, springer spaniels, and smooth fox terriers. A congenital Seronegative MG may occur because there are anti-
MG was described in three 8‐week‐old miniature smooth‐ bodies directed against non‐ACHR end plate proteins,
haired dachshunds. These dogs had decreased density of the antibodies are all bound to the endplates with little to
ACh receptors in intercostal muscle biopsy samples with no circulating antibodies, or the antibodies may be lost
no demonstrable AChR antibodies or antibody complexes during the AChR extraction procedure.
demonstrated against the AChR in muscle biopsies. In humans, autoantibodies have been detected against
Interestingly, their clinical signs resolved spontaneously at a receptor tyrosine kinase, MuSK, in about 70% of AChR
six months of age which is not typical but is similar to a seronegative patients. The MuSK enzyme is located on
familial infantile myasthenia described in humans. There the postsynaptic membrane and induces acetylcholine
are a few cats reported with congenital MG. accumulation. A dog with a negative AChR antibody titer
and positive MuSK autoantibodies has been identified.
Diagnosis of Congenital MG The ryanodine receptor (RyR) may also play a role in MG.
The diagnosis of congenital MG should be considered in This channel receptor is responsible for the release of
any young animal with the typical clinical presentation of calcium necessary for muscle contraction. Autoantibodies