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Arquivos de Neuro-Psiquiatria

Print version ISSN 0004-282XOn-line version ISSN 1678-4227

Arq. Neuro-Psiquiatr. vol.66 no.1 São Paulo Mar. 2008

http://dx.doi.org/10.1590/S0004-282X2008000100001 

ARTICLES

 

Neuromyelitis optica: brain abnormalities in a Brazilian cohort

 

Neuromielite óptica: alterações encefálicas em pacientes brasileiros

 

 

Denis Bernardi BichuettiI, III; René Leandro Magalhães RiveroII, IV; Daniel May OliveiraI, III; Nilton Amorin de SouzaI, IV; Nitamar AbdalaII, V; Enedina Maria Lobato OliveiraI, IV, VII; Alberto Alain GabbaiI, VI

INeurology and Neurosurgery Department - Federal University of São Paulo, São Paulo SP, Brazil
IIRadiology Department - Federal University of São Paulo, São Paulo SP, Brazil
IIIPost-Graduate Student of Neurology - Federal University of São Paulo, São Paulo SP, Brazil
IVAssistent Phisician - Federal University of São Paulo, São Paulo SP, Brazil
VHead, Neuroradiology Sector - Federal University of São Paulo, São Paulo SP, Brazil
VIFull Professor, Discipline of Neurology - Federal University of São Paulo, São Paulo SP, Brazil
VIINeurologist Advisory for Schering do Brasil - Federal University of São Paulo, São Paulo SP, Brazil

 

 


ABSTRACT

Neuromyelitis optica (NMO) is a demyelinating disease consisting of relapsing-remitting optic neuritis and myelitis with a more severe course than Multiple Sclerosis. Recently, it has been shown that almost 50% of patients with NMO can have brain magnetic resonance imaging (MRI) abnormalities. We report on six Brazilian patients with NMO, fulfilling the 1999 Wingerchuck criteria for this disease, with abnormal brain MRI and discuss their clinical and radiological features.

Key words: neuromyelitis optica, brain abnormalities, MRI.


RESUMO

Neuromielite óptica (NMO) é doença desmielinizante, remitente-recorrente, com acometimento predominante dos nervos ópticos e medula espinal e uma evolução mais grave comparada à esclerose múltipla. Estudos recentes demonstraram que até 50% dos pacientes com NMO podem apresentar lesões encefálicas à ressonância magnética (RM). Relatamos seis pacientes brasileiros com NMO, que satisfazem os critérios diagnósticos de Wingerchuck (1999) para NMO, com alterações encefálicas em RM de encéfalo e discutimos seus dados clínicos e de imagem.

Palavras-chave: neuromielite óptica, alterações encefálicas, ressonância magnética.


 

 

Neuromyelitis optica (NMO), also known as Devic's syndrome or Devic's disease, is a demyelinating disease with predilection for the optic nerve and spinal cord1,2. It was first considered to have a monophasic course and to be a multiple sclerosis (MS) variant, but data gathered in the past few years have shown NMO to be a relapsing disease with clinical behavior and pathology distinctive from MS1,3. The first Brazilian reports on NMO have also disclosed extensive demyelination in the optic nerves and spinal cord4,5.

The first attempt to establish diagnostic criteria for NMO demanded the occurrence of optic neuritis (uni or bilateral) and acute myelitis with no restriction on the timeframe over which the first attacks of optic neuritis and myelitis occur (index event), and no evidence of disease outside the optic nerve and spinal cord2. Neurologists have thus been reluctant to diagnose NMO in someone with brain scan abnormalities, even though these abnormalities do not fulfill the criteria for MS6.

Therefore, we sought to survey our NMO patient's records in search of cases with brain MRI abnormalities and discuss their disease course.

 

METHOD

We retrospectively reviewed records of 63 patients attended at the Federal University of São Paulo Hospital Neuroimmunology Clinic, Brazil, from 1994 to 2006, who presented with a recurrent idiopathic demyelinating disease, predominantly affecting the optic nerves and spinal cord. Apart from the clinical course they had spinal cord lesions longer than three vertebral segments and brain magnetic resonance imaging (MRI) abnormalities not fulfilling MS criteria, thus meeting the 1999 criteria for NMO2. Based solely on the records notes, 50% had some form of unspecific brain MRI abnormality. We selected six of these patients whose brain MRI were available for evaluation; we collected their clinical and radiological data respectively from medical records and from digital recordings of the Department of Radiology.

 

RESULTS

All patients were seen by at least one of the authors (Dr. Gabbai saw the patients on admission) up to 2006 with a mean follow-up of 3.5 years (range 1-7); their clinical information are shown on Table 1. Briefly, mean age at onset was 24.2 years (range 17-43), Kurtze's Expanded Disease Severity Score (EDSS) on first appointment was 4 (range 4-6) and evolved to 8 (range 4.0-10) on last visit, with a median relapse rate and progression index (last EDSS/disease duration)7,8 of 1.3 (range 1.0-5.0) and 1.4 (range 0.6-9.5) respectively. Four patients underwent cerebrospinal fluid (CSF) analysis, two had abnormal cell count (20 and 15/mm3) and the other two had normal cell count and absence of oligoclonal bands. Patients 3 and 6 responded to azathioprine plus prednisone and patient 4 improved after immunoglobulin therapy, and is currently on regular prednisone plus azathioprine maintenance therapy9. Patient 1 was refractory to all proposed treatments, including prednisone, methylprednisolone, azathioprine, cyclophosphamide, and immunoglobulin. Patients 2 and 5 had a very rapid course with severe disability, despite attempts to use different drug regimens, which included methylprednisolone, cyclophosphamide and azathioprine.

Brain MRI analysis revealed variable signal abnormalities in the spinal cord, concomitant to or extending from the cervical cord lesion in all patients (Figure). There were signal abnormalities in the optic chiasm in all but patient 2 and in the diencephalon in three of them (Patients 1, 4 and 6) (Table 2 ). In patient 4, only slight abnormalities were observed in the midbrain and corpus callosum, whereas in patients 3 and 5 the lesions extended to the midbrain (predominantly to the cerebral peduncles), internal capsule and corpus callosum; patient 5 also showed a few focal signal abnormalities in the periventricular white matter. Patient 1 had the most striking brain involvement with extensive signal abnormalities in the periventricular white matter as well as in the right hippocampus. Patient 2 also had extensive subcortical white matter involvement with hypointense signal on T1- weighted images, suggesting early axonal loss. We observed a variable pattern regarding gadolinium enhancement: absence of enhancement (patient 3), mild punctiform enhancement (patients 4 and 6), corpus callosum enhancement only (patient 2) and nodular enhancement inside the lesions (patients 1 and 5). None of the images evaluated fulfilled the Barkhoff criteria for MS6.

 

 

Five patients had atypical symptoms (1, 2, 3, 4 and 6) including dysphonia, vomiting, hiccups, headache and altered mental status. Although patients 1 and 2 had longer time from the first relapse to index event, the severity of their attacks and unresponsiveness to therapy was remarkable, and both needed respiratory support (Table 1). All patients had predominance of myelitis over optic neuritis attacks.

 

DISCUSSION

We report on a series of Brazilian NMO patients with brain abnormalities. Brain abnormalities in Brazilian patients with NMO have previously been reported10, 11, as also in the original series from the Mayo Clinic2, but until recently it was not know the cause of these lesions.

The identification of an antibody that binds to blood-brain-barrier (BBB) aquaporin 4 channel (NMO-IgG), which is 73% sensitive and 91% specific12,13, has turned NMO into a BBB channelopathy with abnormal humoral immunity activation. This antibody was positive in 68% of NMO patients with atypical brain lesions14 and in 63% patients with the optic-spinal MS15, which also had atypical brain lesion similar to the ones described by Pittock et al.14 . Furthermore, sites of high brain aquaporin 4 expression seems to correspond to brain MRI lesions sites in patients with NMO16. The concept of an abnormal brain MRI in NMO has been recently evaluated in a cohort of sixty patients14 and led to new insights in disease aetiology and its diagnostic criteria17.

Our patients are younger and with higher EDSS scores than the ones described by Pittock et al.14 and Nakashima et al.15, Three of them evolved to severe disability, including the need for respiratory support, which is in accordance with previous reports on the natural history of NMO1,18,19. In the series reported by Pittock et al.14, almost half of the patients with brain MRI abnormalities had a normal scan on first evaluation, only disclosing brain abnormalities during follow-up images14. In our series, all patients but one presented with atypical brain MRI since the initial relapse, but they could not be classified as having MS. Only patient 1 showed extensive brain damage after five years of a relapsing-remitting optic-spinal disease. Possibly, other patients will develop brain lesions over time in a way similar to the ones described by Pittock et al.14; such evolution pattern should prompt neurologists to perform follow-up brain MRI in all NMO patients, regardless of their initial presentation. Testing for the NMO-Ig in our cohort would have reinforced the diagnosis of NMO12,13, but this technique was unavailable in Brazil at time this patients were seen. At last follow-up visit one had died and 2 have reached an EDSS of 9.5 and have returned to their home town, thus making the serology testing not viable. However, due to the clinical presentation and the course of the disease, we are certain that these patients have recurrent NMO, despite their atypical pattern of brain lesions.

The impact of having or not lesions beyond the spinal cord and optic nerve in NMO patients is still uncertain. The pattern of lesion distribution in the brain is clearly different from what is seen in classical MS, but whether it means a more aggressive disease or late-stage Devic's disease, which all patients will reach, is difficult to determine without long-term epidemiological studies.

Treatment of NMO is a challenge since conventional MS therapy is not effective1. The association of prednisone with azathioprine, plasma exchange and immunoglobulin seems to be beneficial9,20,21, and rituximab was shown to be effective in a series of NMO patients and may be a treatment option22. However, it is yet unknown whether patients with brain lesions will respond differently to the available therapies.

In conclusion, anormal brain MRI was once considered a distinctive feature of NMO. Nevertheless, recent data have shown that some patients may have brain MRI lesions which are not typical of MS. The question of whether NMO with brain abnormalities has a more aggressive course and will respond differently to proposed treatments, or is simply the late stage of NMO, remains unanswered. The number of cases described so far and the lack of comparison to patients with normal brain MRI on follow-up prevent us from drawing further conclusions, and long-term studies are needed to answer these questions.

 

REFERENCES

1. Wingerchuk DM. Neuromyelitis optica. Int MS J 2006;13:42-50.        [ Links ]

2. Wingerchuk DM, Hogancamp WF, O'Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic's syndrome). Neurology 1999;53:1107-1114.        [ Links ]

3. Lucchinetti CF, Mandler RN, McGavern D, et al. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain 2002;125:1450-1461.        [ Links ]

4. Assis JL, Maffei WE. Mielite neuro-óptica. Arq Neuropsiquiatr 1945;3:225-233.        [ Links ]

5. Assis JL, Aidar O, Lombardi J. Mielopatia neuro-óptica. Artério e arteriolosclerose: considerações a propósito de um caso anatomo-clínico. Arq Neuropsiquiatr 1951;9:157-170.        [ Links ]

6. Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol 2005;58:840-846.        [ Links ]

7. Weinshenker BG, Bass B, Rice GP, et al. The natural history of multiple sclerosis: a geographically based study: I. Clinical course and disability. Brain 1989;112(Pt 1):133-146.        [ Links ]

8. Cendrowski W. [Nuclear magnetic resonance in multiple sclerosis]. Pol Tyg Lek 1986;41:794-796.        [ Links ]

9. Mandler RN, Ahmed W, Dencoff JE. Devic's neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology 1998;51:1219-1220.        [ Links ]

10. Papais-Alvarenga RM, Miranda-Santos CM, Puccioni-Sohler M, et al. Optic neuromyelitis syndrome in Brazilian patients. J Neurol Neurosurg Psychiatry 2002;73:429-435.        [ Links ]

11. Domingues RB, Kuster GW, Lanes F, Callegaro D. Recurrent neuromyelitis optica with diffuse central nervous system involvement: case report. Arq Neuropsiquiatr 2004;62:543-546.        [ Links ]

12. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004;364:2106-2012.        [ Links ]

13. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005;202:473-477.        [ Links ]

14. Pittock SJ, Lennon VA, Krecke K, Wingerchuk DM, Lucchinetti CF, Weinshenker BG. Brain abnormalities in neuromyelitis optica. Arch Neurol 2006;63:390-396.        [ Links ]

15. Nakashima I, Fujihara K, Miyazawa I, et al. Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG. J Neurol Neurosurg Psychiatry 2006;77:1073-1075.        [ Links ]

16. Pittock SJ, Weinshenker BG, Lucchinetti CF, Wingerchuk DM, Corboy JR, Lennon VA. Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch Neurol 2006;63:964-968.        [ Links ]

17. Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006;66:1485-1489.        [ Links ]

18. Wingerchuk DM, Weinshenker BG. Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology 2003;60:848-853.        [ Links ]

19. Pirko I, Blauwet LK, Lesnick TG, Weinshenker BG. The natural history of recurrent optic neuritis. Arch Neurol 2004;61:1401-1405.        [ Links ]

20. Keegan M, Pineda AA, McClelland RL, Darby CH, Rodriguez M, Weinshenker BG. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 2002;58:143-146.        [ Links ]

21. Weinshenker BG. Therapeutic plasma exchange for acute inflammatory demyelinating syndromes of the central nervous system. J Clin Apher 1999;14:144-148.        [ Links ]

22. Cree BA, Lamb S, Morgan K, Chen A, Waubant E, Genain C. An open label study of the effects of rituximab in neuromyelitis optica. Neurology 2005;64:1270-1272.        [ Links ]

 

 

Received 27 July 2007, received in final form 25 September 2007. Accepted 10 November 2007.

 

 

Dr. Denis Bernardi Bichuetti – Rua Pedro de Toledo 377 - 04039-000 São Paulo SP - Brasil. E-mail: denisbichuetti@globo.com

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