Neuromyelitis Optica

Vinaykumar.V

Physician Assistant, Department of Neurology Kauvery Hospital, Hosur, Tamil Nadu

Introduction

Neuromyelitis Optica (NMO) is an autoimmune disease affecting parts of nervous system. It most commonly affects optic nerves, spinal cord and certain parts of brain, especially brain stem. This condition has undergone name changes over the years. It’s original name, Devic’s disease, comes from Eugène Devic, the French neurologist who first described it. However, an international group of experts gave the condition its current name in 2015. This condition’s full, formal name is neuromyelitis optica spectrum disorder (NMOSD). But it is still commonly called neuromyelitis optica. NMO is caused by a pathogenic serum IgG antibody against the water channel aquaporin-4 (AQP4) in the majority of patients. It binds to AQP4 channels on astrocytes, triggering activation of the classical complement cascade, causing lymphocyte granulocyte, and eosinophil infiltration, culminating in injury first to astrocyte, then oligodendrocytes followed by demyelination and neuronal loss. Most common presentation of NMO is in the form of transverse myelitis and optic neuritis as classically described. But additional presentation includes cranial nerves palsy and damages to the long tracts (due to brainstem involvement), recurrent hiccups, nausea, and vomiting (due to involvement of Area Postrema), narcolepsy like presentation due to diencephalon involvement and other neurologic deficits localizing to cerebral hemispheres. Because of this various presentation of NMO, the terminology of Neuromyelitis optica spectrum disorders (NMOSD) is more apt. Most NMOSD patients experience severe relapses leading to permanent neurological disability, making suppression of relapse frequency and severity, the primary objective in disease management. Relapses are usually treated with pulse IV methylprednisolone. Therapeutic plasma exchange is considered in intravenous steroid refractory cases. Maintenance therapy with immunosuppressive drugs such as oral prednisone, azathioprine, and mycophenolate mofetil has shown benefit in reducing subsequent relapses. Currently, long-term NMOSD relapse prevention includes off-label use of immunosuppressants, particularly rituximab. Of recent, 3 pivotal clinical trials have expanded the spectrum of drugs available for NMOSD patients. Phase III studies have shown significant relapse reduction compared to placebo in AQP4-Ab-positive patients treated with satralizumab, an interleukin-6 receptor (IL-6R) inhibitor, inebilizumab, an antibody against CD19+ B cells; and eculizumab, an antibody blocking the C5 component of complement. However, the cost and availability of these medicines hinder treatment in most of the NMO patients outside research settings. Sivelestat, ublituximab, ravulizumab, and aquaporumab are newer biologics under clinical evaluation.

Who does Neuromyelitis Optica Affect?

NMO is much more likely to affect females, who make up about 80– 90% of cases. It usually affects people between the ages of 30 and 40. NMO in children is very uncommon, making up only 5% or so of cases. People of all races and ethnic backgrounds can develop NMO, but it doesn’t affect people of all backgrounds at the same rates. NMO affects people of African descent, especially African Caribbean descent, at higher rates. The Caribbean Island of Martinique, a French territory, has the highest number of cases for the size of its population, about 10 per 1000,000 people. It can also disproportionately affect people of Asian descent.

Neuromyelitis Optica Spectrum Disorder Diagnostic Criteria

NMOSD with AQP4 – IgG

At least 1 core clinical characteristic (at right)
Positive test for AQP4 – IgG
Exclusion of alternative diagnoses

NMOSD without AQP4- IgG or Uknown AQP4 – IgG Status

At least 2 core clinical characteristics (at right) resulting from 1 or more clinical attacks and satisfying all the following requirements:
At least 1 of: ON, acute myelitis with LETM or APS
Dissemination in space (> 2 different core characteristics)
MRI requirements, if applicable (at right)
Negative tests for AQP4 – IgG or testing unavailable
Exclusion of alternative diagnoses

Core Clinical Characteristics of NMOSD

Most Common	Less Common
Optic neuritis (ON)	Acute brain stem syndrome
Acute myelitis	Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD - Typical diencephalic MRI lesions
Area postrema syndrome (APS); episode of otherwise unexplained hiccups or nausea and vomiting	Symptomatic cerebral syndrome with NMOSD - Typical brain lesion

Supporting MRI requirements for NMOSD without AQP$ – IgG

Acute optica neuritis: Brain MRI normal or demonstrating only nonspecific white matter lesions; or optic nerve MRI with T2 hyperintense lesion or T1 weighted gadolinium enhancing lesion extending over > 1/2 optica nerve length or involving optic chiasm
Acute myelitis: spinal cord MRI showing attack associated lesion extending > 3 contiguous segments (LETM); or > 3 contiguous segments of focal cord atrophy in patients with prior history of acute myelitis
Area postrema syndrome: dorsal medulla / Area postrema MRI lesion
Acute brain stem syndrome: peri – ependymal brain stem lesions.

Case Presentation

25-year-old female presented with complaints of weakness of her right hand for 3 days.

History of Present Illness

She came with C/o tiredness for 3 days H/o Whole body tingling sensation few days and history of neck pain, weakness of right hand for 3 days and history of burning chest sensation.
No H/o Fever / slurring of speech / headache / vomiting

Past History: No comorbidities

On Examination

Conscious, oriented,
Right partial ptosis with miosis
Right hand clawing (+)
Right hand small muscles: weak
Right hand long flexors and Wrist flexors – weak
Wide based ataxic gait
Lhermitte’s sign (+)
Neck muscle tone increased

Vitals

BP – 120/80mmHg
PR – 74/min
RR – 22/min
Temperature –98⁰F
SpO2 – 98% on RA
GRBS – 127mg/dl
Other Systems – Normal

Investigations

Routine Blood Investigations Were Normal

Tests	Values
ANA by indirect immunofluorescence on HEp - 2 cells	Negative
Angiotensin Converting Enzyme	13.92 U/L
Anti-nuclear Antibody screen Plus (IgG)	< 0.50 Ratio
Antibodies for aquaporin (NMO)	Positive
HIV Rapid	Negative
HBsAg	Negative
HCV Rapid	Negative
MS Panel	Negative (no oligoclonal bands in CSF)

MRI Cervical Spine

Extensive increased T2 signal and expansion of the cord (longitudinally extensive spinal cord lesion) is seen extending between C1 and D4, The T2 signal abnormality involves central grey matter and dorsal columns, linear sagittally heterogenous enhancement is seen posterior within the cord suggestive of transverse myelitis, Minimal cervical spondylosis changes, C3-4 to C5-6 disc mild posterior bulge with small posterolateral osteophyte formation indenting the thecal sac and minimal foraminal narrowing, Brachial plexus appears within normal limit, Whole spine survey L5 – S1 and L4-5 disc mild posterior bulge indenting the thecal sac and just touching the traversing nerve root at the lateral recess, Right brachial plexus – No e/o root avulsion or abnormal signal intensity.

Evaluation and Management

After clinical examination, In view of ataxic gait with Lhermitte’s sign, a spinal cord lesion involving the posterior column was suspected, additionally, in view of involvement of long flexors of fingers and wrist (predominantly C6, C7) and small muscles of hands (C8, T1), along with ipsilateral Horner’s syndrome, a longitudinally extending lesion from at least C6 to T1 was suspected in right side of the spinal cord. MRI Cervical spine with contrast was taken. MRI Cervical Spine matched with the clinical findings. Considering longitudinally extending transverse myelitis in spinal cord, differentials considered were demyelinating lesions (NMO, multiple sclerosis, Anti MOG antibody disorders), neuro sarcoidosis, and infective myelitis. CSF study was done which showed micro protein – 66mg/L, Glucose – 86 mg/dL, Cells count – 02 cells/micro/L. She improved with pulse methylprednisolone and other supportive measures including physiotherapy. She was discharged on oral Prednisolone (1mg/kg). On regular follow up she had residual weakness in her right hand and renervation tremors. She also developed cushingoid features. Corticosteroid dose was tapered and steroids sparing therapy was planned. However, she stopped medicines and lost follow up.5 months later, she presented with shooting pain down her spine on flexing her head. She had Lhermitte’s sign. There were no new focal neurologic deficits. She was restarted on corticosteroid and mycophenolate mofetil was also added. After symptomatic improvement and she again stopped medicines despite explaining risk of relapse. She later presented with acute onset weakness of her right hand and leg. On examination she had worsening of neurologic deficits in right upper limb and right foot drop localizing to spinal cord at the level of L5 intramedullary. A relapse of NMO was considered and after relevant investigations. She was treated with pulse methylprednisolone. Further, after her deficits started improving. Rituximab was administered with tapering dose of oral corticosteroids. As of last follow up she was symptomatically better with only residual deficits involving right hand which includes wasting of thenar, hypothenar and interossei with weakness involving small muscles of hand. This case emphasizes the importance of the use of off label medicines like rituximab in devastating conditions like NMO especially in treatment non – compliant cases due to its ease of administration and long term efficancy in preventing relapse.

Conclusion

Patient functional activity improved. We realised that prompt diagnosis and initiation of aggressive immunosuppressive therapy are critical to minimizing the impact of the disease and improving long-term outcomes

Neuromyelitis Optica

Neuromyelitis Optica

Vinaykumar.V

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