HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Correspondence to:

BRIEF COMMUNICATIONS: Marc Gotkine, Yakov Fellig, and Oded Abramsky Occurrence of CNS demyelinating disease in patients with myasthenia gravis Neurology 2006; 67: 881-883 [Abstract] [Full text] [PDF]

Correspondence: Submit a response to this article

Correspondence published:

Occurrence of CNS demyelinating disease in patients with myasthenia gravis

Brian G. Weinshenker, Anu Jacob   (4 December 2006)

Occurrence of CNS demyelinating disease in patients with myasthenia gravis

Ken Ikeda, Yo Araki, and Yasuo Iwasaki.   (4 December 2006)

Occurrence of CNS demyelinating disease in patients with myasthenia gravis

Ilya Kister, Joseph Herbert, Michael L. Swerdlow, Roberto Bergamaschi, Giovanni Piccolo and Joel Oger   (4 December 2006)

Reply from the Authors

Marc Gotkine, Oded Abramsky   (4 December 2006)

Occurrence of CNS demyelinating disease in patients with myasthenia gravis 4 December 2006
Brian G. Weinshenker, Department of Neurology, Mayo Clinic College of Medicine W8B,Mayo Clinic College of Medicine,200 First St SW ,Rochester MN 55905 USA, Anu Jacob Send Correspondence to journal: Re: Occurrence of CNS demyelinating disease in patients with myasthenia gravis weinb{at}mayo.edu Brian G. Weinshenker, et al.	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.
Occurrence of CNS demyelinating disease in patients with myasthenia gravis 4 December 2006
Ken Ikeda, Department of Neurology, PL Tokyo Health Care Center 16-1, Kamiyamacho, Shibuyaku, Tokyo, 150-0047, Japan, Yo Araki, and Yasuo Iwasaki. Send Correspondence to journal: Re: Occurrence of CNS demyelinating disease in patients with myasthenia gravis keni{at}pl-tokyo-kenkan.gr.jp Ken Ikeda, et al.	We read with great interest the article by Gotkine et al [1] concerning occurrence of CNSDD and myasthenia gravis (MG). We also encountered one patient with recurrent myelitis among 325 patients with MG. A 53-year-old woman was diagnosed as MG at age 29. Thymectomy was performed at age 30 years and the pathologic finding revealed hyperplasia. After she was treated with pyridostigmine and prednisolone until age 42 years, MG was remitted completely without medication. Three years later, she developed weakness and dysesthesisa in the upper limbs. Cervical MRI showed T2-hyperintensity signal areas in the C2-6 segments with enhancement. Methylprednisolone treatment improved motor and sensory deficits without sequences. She experienced paresthesia ascending from the lower limbs to body and upper limbs and painful tonic seizures in the upper limbs at age 51. Neurological examination showed paresthesia and hyperreflexia in the four extremities and Lhermitte's sign was presented. Immunological analyses showed negative acetylcholine receptor antibodies and increased anti-nuclear antibodies. Brain MRI was normal. Spinal MRI disclosed T2-hyperintensity signal areas in the C3-T1 segments with ring-shaped enhancement. On visual evoked potentials, P100 latency was delayed (115 msec in the right and 118 msec in the left). Two years later, optic neuritis occurred. The final diagnosis of neuromyelitis optica (NMO) was made. According to recent diagnostic criteria for NMO, [6] the features of spinal MRI reveal longitudinally extensive cord lesions more than three segments in our and four patients of Gotkine et al. [1] Those pathognomic distribution of spinal lesions suggest a possibility of NMO. Gotkine et al [1] describe that prolonged visual evoked potentials in Patient 4. The first question is whether visual evoked potentials are performed in Patient 1, 3 and 5. The first question is whether visual evoked potentials are performed in the other four patients. We would like to know serum NMO-IgG antibodies in Patient 1 and 5 who have no lesions on brain MRI. How is the possibility of NMO in those patients? NMO is associated in MG patients after thymectomy. [4,7] Besides NMO, recurrent myelitis without optic neuritis could contribute to common immunological mechanism as a subgroup of CNSDD in thymectomized MG patients. References 6. Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006; 66: 1485-1489. 7. Furukawa Y, Yoshikawa H, Yachie A, Yamada M. Neuromyelitis optica associated with myasthenia gravis: characteristic phenotype in Japanese population. Eur J Neurol 2006; 13: 655-658. Disclosure: The authors report no conflicts of interest.
Occurrence of CNS demyelinating disease in patients with myasthenia gravis 4 December 2006
Ilya Kister, NYU/Hospital for Joint Diseases 301 East 17th Sreet, Suite 550, New York, NY 10003, Joseph Herbert, Michael L. Swerdlow, Roberto Bergamaschi, Giovanni Piccolo and Joel Oger Send Correspondence to journal: Re: Occurrence of CNS demyelinating disease in patients with myasthenia gravis ilya.kister{at}mssm.edu Ilya Kister, et al.	Gotkine et al [1] describe three patients with myasthenia gravis (MG) who underwent thymectomy and subsequently developed either recurrent or monophasic acute myelitis. The authors suggest that these patients may have a "form fruste of SLE", given their elevated ANA titers, though they have not exhibited any non-neurologic manifestations of SLE and had no anti-ds DNA Ab in serum. Alternatively, we would like to propose that the three patients may have form fruste of Neuromyelitis Optica (NMO). ANA positivity is not an infrequent finding in NMO [8] and would not preclude this diagnosis. All three patients had extensile cord lesions three or more vertebral segments in length, which are highly characteristic of NMO; absence of MS-like plaques in brain and oligoclonal bands in CSF is also suggestive of this disease. It would be interesting to examine the patients for stigmata of past attacks of optic neuritis on neuro-ophthalmologic exam and on visual evoked potentials, as well as to test their NMO IgG status. We recently reported four patients with MG who underwent thymectomy and developed clinically definite NMO; two of our four patients had an elevation in ANA titers. [4]. Concurrently, Furukawa et al, published two cases of MG followed by NMO: one patient had thymectomy prior to NMO onset, while the other has been previously diagnosed with SLE [7]. There are presently no less than 13 reports in the literature of thymectemized myasthenics developing NMO, or recurrent acute myelitis. [4,7,9 and references therein]. In all these cases, MG was diagnosed prior to the first CNS event. Moreover, in all but one patient with definite MG and NMO, thymectomy preceded NMO onset. We agree with the conjecture of Gotkine et al that thymectomy may lead to breakdown of self-tolerance thereby potentiating development of autoimmune disease. A systematic analysis of long-term effects of thymectomy is needed, using non-thymectomized myasthenics as controls, to assess whether thymectomy indeed confers an increased risk of future autoimmune disease and what the magnitude of the excess risk is. It may also be worthwhile to investigate whether thymectomy predisposes to development of NMO IgG autoantibodies even in the absence of clinical manifestations of NMO. References 8. Ghezzi A, Bergamaschi R, Martinelli V, et al. Clinical characteristics, course and prognosis of relapsing Devic’s Neuromyelitis Optica. J Neurol 2004; 251:47-52. 9. Antoine J-C, Camdessanche J-P, Absi L, Lassabliere F, Feasson L. Devic disease and thymoma with anti-central nervous system and antithymus antibodies Neurology 2004 62: 978-980. Disclosure: The authors report no conflicts of interest.
Reply from the Authors 4 December 2006
Marc Gotkine, Department of Neurology, Hadassah University Hospital P.O. Box 12000, Jerusalem 91120, Israel, Oded Abramsky Send Correspondence to journal: Re: Reply from the Authors marcgotkine{at}gmail.com Marc Gotkine, et al.	We thank the authors for raising some important questions which reiterate the importance of the discovery by Dr. Weinshenker's group of the NMO-IgG and its value in defining patients with a distinct spectrum of diseases. We agree with Drs Weinshenker and Jacob, Dr. Ikeda et al and Dr. Kister et al that the extensive longitudinal involvement of the spinal cord with cord swelling is characteristic of the type of myelitis occurring in patients with NMO-IgG. We also would point out that this type of spinal cord lesion also occurs in patients with SLE. [10] As SLE is a syndrome with clinical criteria we once again emphasize that none of our patients had SLE (hence we defined the syndrome as a "forme fruste") although we stand by our assertion that the neurological involvement observed in some of our patients may be due to pathogenetic mechanisms which also occur in SLE. [1] Ikeda et al make a valid point regarding visual evoked potentials (VEP). Although not fully detailed in our original paper these were normal in patient 1 and abnormal in patients 3 and 4. Unfortunately patient 5 had not performed a VEP test and was unavailable for further testing. We are impressed by the close resemblance of clinical and laboratory features between Dr. Ikeda's patient and our patient 1. The most noteworthy difference is the clinical and electrophysiological evidence of optic nerve dysfunction in Dr. Ikeda's patient whereas our patient 1 has never suffered from visual symptoms and had normal visual evoked potentials bilaterally. NMO-IgG has been reported in patients with MG with classic NMO [4] but has not yet been documented in patients with MG and isolated myelitis. Nevertheless, prior to the publication of our article we sent serum from patient 1 (relapsing longitudinal myelitis) and patient 3 (relapsing localized myelitis) for NMO-IgG testing. Not surprisingly, patient 1 (the patient discussed by Weinshenker and Jacob and Ikeda et al) but not patient 3, tested positive for NMO-IgG. Given that NMO occurs in patients with SLE [11] it is certainly conceivable that the myelitis of SLE is closely related, if not part of the NMO spectrum. As a corollary we hypothesize that systematic investigation of SLE patients with longitudinal myelitis will reveal a high proportion of patients with NMO-IgG. References 10. Krishnan AV, Halmagyi GM. Acute transverse myelitis in SLE. Neurology 2004;62(11):2087-. 11. Jacobi C, Stingele K, Kretz R, et al. Neuromyelitis optica (Devic's syndrome) as first manifestation of systemic lupus erythematosus. Lupus 2006;15(2):107-109. Disclosure: The authors report no conflicts of interest.