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Case Report

A case of Neuromyelitis optica as a presentingmanifestation of Systemic Lupus Erythematosis

V.L. Arul Selvan

Consultant Neurologist, Apollo Institute of Neurosciences, Chennai 600078, India

a r t i c l e i n f o

Article history:

Received 25 July 2013

Accepted 7 August 2013

Available online 4 September 2013

Keywords:

Neuromyelitis optica

Antiaquaporin antibody

Hypothyroidism

Catheter

E-mail address: drarulselvan@yahoo.com0976-0016/$ e see front matter Copyright ªhttp://dx.doi.org/10.1016/j.apme.2013.08.005

a b s t r a c t

Neuromyelitis optica (NMO) is a well characterised, autoimmune, clinicopathological

syndrome, which is uncommon and occurs as an isolated entity. Unlike multiple sclerosis,

in NMO, the autoimmunity is humorally mediated and the recent availability of Anti-

aquaporin antibody testing has increased the positive diagnosis of this condition. NMO can

also occur in patients with established Systemic Lupus Erythematosis (SLE) who have

multiple autoantibodies. The presence of Antiaquaporin antibody is specific for NMO and is

seen in patients with SLE who develop inflammatory CNS disease. However, Neuromyelitis

optica occurring as a presenting manifestation of SLE is extremely rare and we report one

such case.

Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.

1. Case report jerks were brisk, Supinator and Knee jerks were sluggish and

A 51-year-old female came to the hospital with history of

constricting pain over the thorax bilaterally of 3 days duration

withweakness of both lower limbs and acute urinary retention

of one day duration. There was no history of fever or trauma.

Her past history consisted of 15 years of hypothyroidism, hy-

pertension of 6 years duration, Diabetes of 10 years and pe-

ripheral vascular disease of 5 years duration with past history

of DVT of left leg for which she was on Acitrome, clopidogrel,

Levothyroxine, oral hypoglycemics and amlodipine. Therewas

no previous neurological illness. No history of prolonged fever,

joint pains, skin lesions or renal impairment. On neurological

examination, she was Alert and oriented and her speech and

cranial nerve examination were normal. She had Quad-

riparesis with a power of 4/5 in the upper limb and a power of

1/5 at hip, 2/5 at knee and 3/5 distally. Abdominal reflex was

absent and plantars were extensor. The Biceps and Triceps

.2013, Indraprastha Medic

Ankle jerk was absent. Vibration sense was reduced in the

lower limbs and touch was impaired below T5. Pain sensation

was reduced below T9. There was no spinal tenderness or

deformity. She was catheterised in view of the urinary reten-

tion. A clinical diagnosis of Acute myeloradiculopathy at the

cervicodorsal level was made and patient was further inves-

tigated. MRI revealed longitudinally extensive myelitic

changes from C5 to the conus with faint enhancement with

contrast (Fig. 1). CSF study revealed a Protein of 110 mg/dl with

glucose of 92 mg/dl and 100 RBCs and 110 WBCs with 92%

lymphocytes. Routine Blood investigations were normal and

ESR was 2 mm/h and Sr Creatinine was 0.5 mg/dl. VEP was

normal. A diagnosis of Acute Disseminated Encephalomyelitis

was made and the patient started on 5 sittings of Plasma ex-

change of 2.5 L each. The patient was managed by a multi-

specialitymedical team for her systemic problems. The patient

started improving by the 4th cycle and was discharged on the

al Corporation Ltd. All rights reserved.

Fig. 1 e a: STIR image showing longitudinally extensive myelitis. b: Axial T2 image at dorsal level showing hyperintensity

in the centre of the dorsal cord.

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11th day when she was able to walk with support with Urinary

catheter in situ. After 4 weeks she had almost completely

recovered and the catheter was removed.

10 months from the initial event, she came back with

transient blurring of vision of right eye associated with

numbness of the right upper limb with slipping of objects

from the hand. MRI Brain revealed a flame shaped lesion in

the left frontoparietal white matter with faint enhancement

with the possibility of demyelination infarct (Fig. 2). VEP done

Fig. 2 e a: Diffusion Weighted Image showing the acute infarct i

the flame shaped lesion (the 2nd episode occurred 10 months a

showed prolongation of P100 latency on the right side and CSF

study was normal. She was treated with 3 days of Solumedrol.

She improved completely in one month.

21 months after the initial event she got readmitted with

history of loss of appetite and loss of weight of 3 months

duration with intermittent low grade fever followed by 2 day

history of weakness of all four limbs (4/5) with bladder

retention and right inferior quadrantanopia. MRI revealed

longitudinally extensive lesion from C5 to lower dorsal with

n the left parietal region. b: FLAIR coronal imaging showing

fter the 1st neurological event).

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patchy lesion in the left occipital lobe (Fig. 3). Her ESR was

100mm/h and CRPwas normal. Shewas started on a course of

IV Solumedrol 1 g/day for 5 days with Plasma exchange of 5

cycles. She again made a remarkable recovery.

At this point, Antiaquaporin-4 antibodywas tested positive

and she was diagnosed as Neuromyelitis optica. She had

sudden drop in Hemoglobin and Coombs test became positive.

Her ANA and dsDNA were also strongly positive. C3 and C4

levels were reduced. Her clinical picture fulfilled the criteria

for Systemic Lupus Erythematosis. Antiphospholipid anti-

bodies were negative. A diagnosis of Neuromyelitis optica in

the setting of SLE was made and she was started on oral ste-

roids along with Mycophenolate, which was later changed to

Azathioprine due to leucopenia.

2. Discussion

Themost widely accepted diagnostic criteria for NMO is: optic

neuritis and acute myelitis with atleast 2 of the following 3: 1.

Spinal cord MRI lesion extending over 3 or more vertebral

segments. 2. Brain MRI not meeting diagnostic criteria for MS

and 3. Positive Antiaquaporin-4 antibody in serum.1 In 2004, a

specific pathogenic antibody called NMO-IgG was discovered.

Fig. 3 e a: Sagittal T2W image showing the hyperintensity main

after the first). b: Left occipital patchy hyperintensity in axial FL

This antibody is targeted against the aquaporin-4 (AQP4)

water channel widely expressed in the optic nerves, the spinal

cord and the periventricular regions. This discovery clearly

placed NMO in the B-cell disease category, which from a

pathophysiological perspective mimics vasculitis rather than

MS.2 Binding of NMO-IgG to AQP4 expressed at the astrocyte

membrane can initiate complement activation and

complement-dependent cytotoxicity. Antiaquaporin-4 anti-

body also damages oligodendrocytes through an excitotoxic

mechanism resulting from glutamate homeostasis disruption

in astrocytes.3

With wider availability of Antiaquaporin antibody, the

clinical spectrum of NMO has widened and includes patients

with isolated severe optic neuritis with poor recovery and dor-

sal brainstem lesions with persistent hiccups and nausea.4,5

Neuropsychiatric manifestations occur in 50% of patients

with SLE sometime in the course of their illness but presen-

tation with neurological illness is seen in less than 3% of pa-

tients. In SLE, headache (54%) and seizures (42%) are the

commonest CNS manifestations.6 The other important man-

ifestations are psychosis, dementia, stroke, myelopathy, pe-

ripheral neuropathy and cranial nerve involvement.7 There

are several case reports of the association of NMO with SLE.

The proposed explanation is a shared environmental/genetic

ly in the dorsal cord (the 3rd episode happened 21 months

AIR image.

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predisposition to autoimmunity.8 Neuromyelitis optica

mostly occurs in the setting of established SLE. However, NMO

presenting as the first manifestation of SLE is extremely rare

and there is an isolated case report of a patient who developed

clinical SLE 7 years after the onset of NMO.9

NMO antibodies are uncommon in SLE and in one study

among 326 patients with SLE including 6 patients with

neurological involvement, only 1 patient tested positive and

he had myelitis.10 In another series of patients with connec-

tive tissue disorderswith neurological involvement consistent

with NMO, aquaporin-4 antibody was positive in 78% of in-

dividuals whereas it was negative in all the patients without

CNS involvement. Hence Antiaquaporin antibody is not a

nonspecific autoantibody seen in SLE and its presence signi-

fied CNS disease consistent with NMO.11,12 On the contrary,

ANA positivity is common in NMO and often is nonspecific. In

one study, ANA was positive in 43.8% of patients with NMO

spectrumdisease, whereas only 2% of patients fulfilled criteria

for SLE.12

NMO is distinctly different from multiple sclerosis in clin-

ical manifestation, etiopathogenesis and response to treat-

ment and the use of the NMO antibody may help to

differentiate the two in difficult situations. Compared to MS,

patients with NMOmay be left with severe permanent deficits

even after a single clinical event, hence differentiating the two

early has important practical implications. Unlike in MS, the

interferon activity is increased in SLE and NMO and this may

explain the worsening that is often seen when interferon is

used in SLE or NMO.13 Plasma exchange is effective in NMO

but has no role in MS. Relapse prevention is by immunomo-

dulation in MS and by immunosuppression in NMO.

In NMO, the initial treatment of choice is Pulse IV meth-

ylprednisolone and patients who do not show a quick

response are treated with Plasma exchange. The response to

treatment in NMO is highly variable, but there are several

reports of individual patients with NMO and SLE who have

responded remarkably to either glucocorticoids or Plasma

exchange over prolonged periods of upto 35 years.14 In one

report Cyclophosphamide was used successfully in 2 patients

who had a overlap of NMO and SLE.15 In patients with re-

fractory NMO, Rituximab is recently being recommended.4

The interesting features in the present patient are 1. Pres-

ence of multiple comorbidities. 2. Having two attacks of NMO

prior to the development of clinical SLE. 3. Dramatic response

to Plasma exchange during both the attacks of extensive

myelitis. 4. Two attacks involving the brain.

3. Conclusion

NMO is a CNS demyelinating disease with a characteristic

presentation and now, has a distinct biomarker. It may be

associated with other autoimmune diseases, especially

SLE and Sjogren’s syndrome. A high index of suspicion is

necessary to diagnose one, when the other disease is present.

An early and aggressive immunosuppressive treatment is

imperative in patients with NMO to prevent devastating

sequelae.

Conflicts of interest

The author has none to declare.

r e f e r e n c e s

1. Wingerchuk DM, Lennon VA, Pittock SJ, et al. Reviseddiagnostic criteria for neuromyelitis optica. Neurology.2006;66:1485e1489.

2. Sato Douglas Kazutoshi, Nakashima Ichiro,Takahashi Toshiyuki, et al. Aquaporin-4 antibody-positivecases beyond current diagnostic criteria for NMO spectrumdisorders. Neurology. 2013;80:2210e2216.

3. Marignier Romain, Giraudon Pascale, Vukusic Sandra,Confavreux Christian, Honnorat Jerome. Anti-aquaporin-4antibodies in Devic’s neuromyelitis optica: therapeuticimplications. Ther Adv Neurol Disord. 2010;3:311.

4. Collongues Nicolas, de Seze Jerome. Current and futuretreatment approaches for neuromyelitis optica. Ther AdvNeurol Disord. 2011;4:111 originally published online 4 March2011.

5. Wang KC, Lee CL, Chen SY, Lin KH, Tsai CP. Prominentbrainstem symptoms/signs in patients with neuromyelitisoptica in a Taiwanese population. Clin Neurosci. 2011Sep;18(9):1197e1200.

6. Joseph Fady G, Alistair Lammie G, Scolding Neil J. CNS lupus:a study of 41 patients. Neurology. 2007;69:644e654.

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9. Jacobi C. Neuromyelitis optica as first manifestation ofsystemic lupus erythematosus. Lupus. 2006;15(2):107e109.

10. Katsumata Y, Kawachi I, Kawaguchi Y, et al. Semiquantitativemeasurement of aquaporin-4 antibodies as a possiblesurrogate marker of NMO spectrum disorders with systemicautoimmune diseases. Mod Rheumatol. 2012Sep;22(5):676e684.

11. Jarius S, Jacobi C, de Seze J, et al. Frequency and syndromespecificity of antibodies to aquaporin-4 in neurologicalpatients with rheumatic disorders. Mult Scler. 2011Sep;17(9):1067e1073.

12. Pittock Sean J, Lennon Vanda A, de Seze Jerome.Neuromyelitis optica and non organ-specific autoimmunity.Arch Neurol. 2008 Jan;65(1):78e83.

13. Feng X, Reder NP, Yanamandala M. Type I interferonsignature is high in lupus and NMO but low in multiplesclerosis. J Neurol Sci. 2012 Feb 15;313(1e2):48e53.

14. Margaux J, Hayem G, Meyer O, Kahn MF. Systemic lupuserythematosus with optical neuromyelitis (Devic’ssyndrome). A case with a 35-year follow-up. Rev Rhum Engl Ed.1999 Feb;66(2):102e105.

15. Polgar A, Rozsa C, Muller V, Matolcsi J, Poor G, Kiss EV. Devic’ssyndrome and SLE: challenges in diagnosis and therapeuticpossibilities based on two overlapping cases. Autoimmun Rev.2011 Jan;10(3):171e174.

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