Clinical Characteristics, Course And Prognosis Of Relapsing Devic's NeuroMyelitis Optica
Italian Devic's Study Group (IDESG)
Ghezzi A, Bergamaschi R, Martinelli V, Trojano M, Tola MR, Merelli E, Mancardi L, Gallo P, Filippi M, Zaffaroni M, Comi G
J Neurol 2004 Jan;251(1):47-52
Centro Studi Sclerosi Multipla-Ospedale di Gallarate, Via Pastori 4, 21013 Gallarate, Italy
To evaluate the clinical characteristics, course and prognosis of Devic's NeuroMyelitis Optica (DNO), to evaluate the prognostic role of demographic and clinical features, to evaluate the current DNO diagnostic criteria.
Demographic, clinical, CSF and MRI data of patients affected by DNO were collected from fifteen Italian MS Centers.
Inclusion criteria were:
1) Two or more acute episodes of Neurological dysfunction indicating involvement of the Optic Nerve and Spinal Cord, in a simultaneous or subsequent temporal relationship;
2) No evidence of lesions beyond the Optic Nerve or the Spinal Cord;
3) Brain MRI at onset negative or non-specific for Multiple Sclerosis (MS) (White Matter lesions < or = 2).
Disability was scored by means of Kurtzke's Expanded Disability Status Scale (EDSS).
46 patients with Relapsing DNO were included, 37 females and 9 males, with mean age at onset of 40.1 +/- 16.3 years (range 12-77 years).
The follow up duration was 8.8 +/- 3.5 years, the mean annualized relapse rate was 1.3 +/- 1.2.
After 5, 10 and 15 years EDSS 3.0 was reached respectively by 65%, 82 % and 86% of cases. EDSS 6.0 respectively by 42%, 53 % and 69% of cases, EDSS 10 respectively by 8%, 12% and 23% of cases.
The probability of reaching EDSS 3 was statistically correlated with age at onset, interval between the first and 2(nd) attack, and relapse rate.
The probability of reaching EDSS 6.0 was correlated with the residual EDSS at onset and to relapse rate. During the follow up, Brain White Matter lesions appeared in 8 subjects.
Spinal Cord MRI showed lesions extending across 3 or more segments in 39 subjects, only 1 lesion involving 1 segment in 4 subjects, and was normal in 3 subjects.
One or more CSF abnormalities were found at least once in 29/44 patients (65.9 %), the most frequent findings being PleoCytosis (38.6 %), OligoClonal Bands (34.1 %), high protein level (25 %), and high Albumin ratio (20.5 %).
DNO has a poor prognosis in most cases. Compared with MS, DNO patients have a higher age at onset, females are more frequently affected, the course is more severe.
Brain and Spinal Cord MRI permit the differentiation of DNO from MS. CSF supports the probability of DNO if it shows increased cells and proteins.
A Serum AutoAntiBody Marker Of NeuroMyelitis Optica: Distinction From Multiple Sclerosis
Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG
Lancet 2004 Dec 11-17;364(9451):2106-12
Mayo Clinic Rochester, Department of Neurology, Rochester, MN 55905, USA
NeuroMyelitis Optica is an Inflammatory DeMyelinating Disease with generally poor prognosis that selectively targets Optic Nerves and Spinal Cord.
It is commonly misdiagnosed as Multiple Sclerosis. Neither disease has a distinguishing biomarker, but optimum treatments differ. The relation of NeuroMyelitis Optica to Optic-Spinal Multiple Sclerosis in Asia is uncertain.
We assessed the capacity of a putative marker for NeuroMyelitis Optica (NMO-IgG) to distinguish NeuroMyelitis Optica and related disorders from Multiple Sclerosis.
Indirect immunofluorescence with a composite substrate of mouse tissues identified a distinctive NMO-IgG staining pattern, which we characterised further by dual immunostaining.
We tested masked serum samples from 102 North American patients with NeuroMyelitis Optica or with syndromes that suggest high risk of the disorder, and 12 Japanese patients with Optic-Spinal Multiple Sclerosis.
Control patients had Multiple Sclerosis, Other Myelopathies, Optic Neuropathies, and miscellaneous disorders.
We also established clinical diagnoses for 14 patients incidentally shown to have NMO-IgG among 85000 tested for suspected Paraneoplastic Autoimmunity.
NMO-IgG outlines CNS MicroVessels, Pia, Subpia, and Virchow-Robin Space. It partly colocalises with Laminin.
Sensitivity and specificity were 73% (95% CI 60-86) and 91% (79-100) for NeuroMyelitis Optica and 58% (30-86) and 100% (66-100) for Optic-Spinal Multiple Sclerosis.
NMO-IgG was detected in half of patients with high-risk syndromes. Of 14 SeroPositive cases identified incidentally, 12 had NeuroMyelitis Optica or a high-risk syndrome for the disease.
NMO-IgG is a specific marker AutoAntiBody of NeuroMyelitis Optica and binds at or near the Blood-Brain Barrier.
It distinguishes NeuroMyelitis Optica from Multiple Sclerosis. Asian Optic-Spinal Multiple Sclerosis seems to be the same as NeuroMyelitis Optica.
IgG Marker Of Optic-Spinal Multiple Sclerosis Binds To The Aquaporin-4 Water Channel
Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR
J Exp Med 2005 Aug 15;202(4):473-7
Mayo Clinic College of Medicine, Department of Immunology, Rochester, MN 55905, USA
NeuroMyelitis Optica (NMO) is an Inflammatory DeMyelinating Disease that selectively affects Optic Nerves and Spinal Cord.
It is considered a severe variant of Multiple Sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ.
A Serum ImmunoGlobulin G AutoAntiBody (NMO-IgG) serves as a specific marker for NMO.
Here we show that NMO-IgG binds selectively to the Aquaporin-4 water channel, a component of the Dystroglycan protein complex located in Astrocytic foot processes at the Blood-Brain Barrier. NMO may represent the first example of a novel class of Autoimmune Channelopathy.
Activation Of Humoral Immunity And Eosinophils In NeuroMyelitis Optica
Correale J, Fiol M
Neurology 2004 Dec 28;63(12):2363-70
Raul Carrea Institute for Neurological Research, FLENI, Montaneses 2325 (1428), Buenos Aires, Argentina
To study Immunologic alterations in patients with NeuroMyelitis Optica (NMO).
The authors studied 8 patients with NMO together with 16 healthy subjects, 16 patients with Relapsing/Remitting Multiple Sclerosis (RRMS), and 16 patients with Secondary/Progressive MS (SPMS), matched for age and sex, as controls.
Because recent histopathologic studies have demonstrated that active NMO lesions consist of PeriVascular ImmunoGlobulin (Ig) deposition and Eosinophil infiltration.
IL-5, IL-6, IL-12, IgG, and IgM production by Anti-Myelin Oligodendrocyte Glycoprotein (MOG) MonoNuclear Cells in peripheral blood and CSF were selected for study using ELISPOT.
Eotaxin-2 (Eo-2) and Eotaxin-3 (Eo-3) levels were also assessed using ELISA and Eosinophil Cationic Protein (ECP) levels by radioimmunoassay.
MOG-specific responses in CSF showed significant increase in IL-5, IL-6, IgG, and IgM secreting cells in NMO patients.
Compared with patients with RRMS, SPMS and healthy subjects. Interestingly, numbers of IgM secreting cells were significantly higher than identical specificity IgG secreting ones.
Moreover, CSF Eo-2, Eo-3, and ECP levels were also significantly higher in NMO patients compared to all three control populations. Anti-MOG IL-12 secreting cells were increased in CSF and peripheral blood from NMO, RRMS, and SPMS patients when compared to healthy subjects.
These observations suggest that NeuroMyelitis Optica is associated with a major Humoral Immune Response (particularly Anti-MOG IgM production) and Eosinophil activation present exclusively in CSF.
Acute Partial Transverse Myelitis With Normal Cerebral Magnetic Resonance Imaging: Transition Rate To Clinically Definite Multiple Sclerosis
Scott TF, Kassab SL, Singh S
Mult Scler 2005 Aug;11(4):373-7
Drexel University College of Medicine, Allegheny General Hospital, Pittsburgh, PA 15212, USA
To determine the long-term risk of developing Clinically Definite Multiple Sclerosis (CDMS) in patients with Acute Partial Transverse Myelitis (APTM) and normal Cerebral Magnetic Resonance Imaging (MRI) scans.
We retrospectively studied 30 consecutive patients with clinical evidence of APTM. Patients with symmetric severe Acute Transverse Myelitis were considered to have complete Transverse Myelitis and were excluded.
All patients underwent Spinal and Cerebral MRIs, 13 underwent CerebroSpinal Fluid analysis and 11 patients underwent Evoked Potential studies.
Various other studies were performed to assess for connective tissue disease and causes of APTM other than DeMyelinating Disease.
After an average follow-up of 61 months, all laboratory and clinical evidence, including relapse history, indicated that three patients developed lesions on Cerebral MRI and could be classified as CDMS by either Poser criteria (two patients) or McDonald criteria (one patient).
Relapses limited to the Spinal Cord seen clinically were seen in 14/30 (46.6%) patients. OligoClonal Bands were seen in 8/13 (62%) patients; one patient transitioned to CDMS.
Unifocal lesions of the Cord were seen in 19/30 (63%) patients, multifocal lesions were seen in 8/30 (27%) and 3/30 (10%) had negative MRIs. The three patients who converted to CDMS did so within five years of the onset of Myelitis.
APTM with normal Cerebral MRI had a low rate of conversion to CDMS in this long-term study. To date, there have been only a few follow-up studies that have addressed this issue.