Occurrence of CNS demyelinating disease in patients with myasthenia gravis
Brian G.Weinshenker, Department of Neurology, Mayo Clinic College of Medicine, W8B,Mayo Clinic College of Medicine,200 First St SW ,Rochester MN 55905 USAweinb@mayo.edu
Anu Jacob
Submitted December 04, 2006
We read with interest the article by Gotkine et al who suggest an
association between myasthenia gravis(MG), "CNS-specific demyelinating
disease" and a "forme fruste of SLE", in a series of five patients. [1] We
suggest a more specific neurological diagnosis for these patients.
Patients 1, 3, and 5 had MG, ANA, and subsequently presented with
myelitis or recurrent myelitis. Patient 1, a 28-year-old woman had two
episodes of longitudinally extensive transverse myelitis (LETM, initially
from C4 to C6; subsequently from C2 to T10) with edema and
enhancement. The brain MRI was normal. This description is more consistent
with the newly recognized neuromyelitis optica (NMO) spectrum of
disorders. [2]
NMO (also known as optic-spinal MS or Devic’s disease) is an
idiopathic inflammatory demyelinating disorder of the CNS characterized by
LETM and optic neuritis (ON), and usually has a relapsing course. 'Mixed'
CSF pleocytosis, as in this case, occasionally with neutrophil
predominance, absence of oligoclonal bands, and lack of brain lesions on
MRI are typical. Relapsing optic neuritis or relapsing myelitis, often
represent limited forms of the NMO phenotype ("NMO spectrum disorders")
and a high proportion of these cases are seropositive for the NMO-specific
autoantibody, NMO-IgG, which is directed at the astrocytic water channel
protein aquaporin-4. [3] The sensitivity of NMO-IgG for the diagnosis of NMO
is 73 percent and specificity 90 percent. Its sensitivity for relapsing
LETM is 52% for first event LETM is 40%. [2,3] In a prospective study of
patients who experienced a first event LETM, NMO-IgG seropositivity
predicted with greater than 50% certainty recurrence of LETM or
development of ON within one year. [2] NMO is recognized to be associated
with other autoimmune disorders in up to 40 percent of cases. Its
association with MG has been documented in several reports. [4]
None of the patients in this report seem to satisfy the ARA
criteria for SLE. ANA is non-organ-specific autoantibody associated with a
variety of immune reactions. Our group recently reported that patients
with NMO spectrum disorders who are seropositive for NMO-IgG have a higher
rate of seropositivity for ANA and SSA/SSB antibodies than those who are
seronegative for NMO-IgG. [5] We suggest that the diagnosis
suggested by Gotkine et al of a "CNS-specific demyelinating disorder",
occurring with MG and a "forme fruste of SLE" is most likely an NMO
spectrum disorder. Testing for NMO-IgG would be helpful for diagnosis and
prognosis.
References
1. Gotkine M, Fellig Y, Abramsky O. Occurrence of CNS demyelinating
disease in patients with myasthenia gravis. Neurology 2006;67:881-883.
2. Weinshenker BG, Wingerchuk DM, Vukusic S, et al. Neuromyelitis optica IgG predicts relapse after
longitudinally extensive transverse myelitis. Ann Neurol 2006;59:566-569.
3. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica:
distinction from multiple sclerosis. Lancet 2004;364:2106-2112.
4. Kister I, Gulati S, Boz C, et
al. Neuromyelitis optica in patients with myasthenia gravis who underwent
thymectomy. Arch Neurol 2006;63:851-856.
5. Pittock SJ, Lennon VA, Wingerchuk DM, Homburger HA, Lucchinetti
CF, Weinshenker BG. The prevalence of non-organ-specific autoantibodies
and NMO-IgG in neuromyelitis optica (NMO) and related disorders. Neurology
2006; 66(5 Suppl 2):A307.
Disclosure: Dr. Weinshenker will receive royalties related to a patent for NMO-IgG held by Mayo Medical Ventures. Dr. Jacob reports no conflicts of interest.
We read with interest the article by Gotkine et al who suggest an association between myasthenia gravis(MG), "CNS-specific demyelinating disease" and a "forme fruste of SLE", in a series of five patients. [1] We suggest a more specific neurological diagnosis for these patients.
Patients 1, 3, and 5 had MG, ANA, and subsequently presented with myelitis or recurrent myelitis. Patient 1, a 28-year-old woman had two episodes of longitudinally extensive transverse myelitis (LETM, initially from C4 to C6; subsequently from C2 to T10) with edema and enhancement. The brain MRI was normal. This description is more consistent with the newly recognized neuromyelitis optica (NMO) spectrum of disorders. [2]
NMO (also known as optic-spinal MS or Devic’s disease) is an idiopathic inflammatory demyelinating disorder of the CNS characterized by LETM and optic neuritis (ON), and usually has a relapsing course. 'Mixed' CSF pleocytosis, as in this case, occasionally with neutrophil predominance, absence of oligoclonal bands, and lack of brain lesions on MRI are typical. Relapsing optic neuritis or relapsing myelitis, often represent limited forms of the NMO phenotype ("NMO spectrum disorders") and a high proportion of these cases are seropositive for the NMO-specific autoantibody, NMO-IgG, which is directed at the astrocytic water channel protein aquaporin-4. [3] The sensitivity of NMO-IgG for the diagnosis of NMO is 73 percent and specificity 90 percent. Its sensitivity for relapsing LETM is 52% for first event LETM is 40%. [2,3] In a prospective study of patients who experienced a first event LETM, NMO-IgG seropositivity predicted with greater than 50% certainty recurrence of LETM or development of ON within one year. [2] NMO is recognized to be associated with other autoimmune disorders in up to 40 percent of cases. Its association with MG has been documented in several reports. [4]
None of the patients in this report seem to satisfy the ARA criteria for SLE. ANA is non-organ-specific autoantibody associated with a variety of immune reactions. Our group recently reported that patients with NMO spectrum disorders who are seropositive for NMO-IgG have a higher rate of seropositivity for ANA and SSA/SSB antibodies than those who are seronegative for NMO-IgG. [5] We suggest that the diagnosis suggested by Gotkine et al of a "CNS-specific demyelinating disorder", occurring with MG and a "forme fruste of SLE" is most likely an NMO spectrum disorder. Testing for NMO-IgG would be helpful for diagnosis and prognosis.
References
1. Gotkine M, Fellig Y, Abramsky O. Occurrence of CNS demyelinating disease in patients with myasthenia gravis. Neurology 2006;67:881-883.
2. Weinshenker BG, Wingerchuk DM, Vukusic S, et al. Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis. Ann Neurol 2006;59:566-569.
3. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004;364:2106-2112.
4. Kister I, Gulati S, Boz C, et al. Neuromyelitis optica in patients with myasthenia gravis who underwent thymectomy. Arch Neurol 2006;63:851-856.
5. Pittock SJ, Lennon VA, Wingerchuk DM, Homburger HA, Lucchinetti CF, Weinshenker BG. The prevalence of non-organ-specific autoantibodies and NMO-IgG in neuromyelitis optica (NMO) and related disorders. Neurology 2006; 66(5 Suppl 2):A307.
Disclosure: Dr. Weinshenker will receive royalties related to a patent for NMO-IgG held by Mayo Medical Ventures. Dr. Jacob reports no conflicts of interest.