Neuromyelitis Optica Flashcards
Neuromyelitis Optica (Delvic Disease)
Neuromyelitis optica (Devic disease) should be suspected when the following is noted:
- quadriparesis or paraparesis within days to weeks
- vision changes
- normal brain MRI
- presence of anti-NMO antibodies (anti-aquaporin 4 antibodies)
- responsive to immunosuppressants
Neuromyelitis optica (NMO) is monophasic or relapsing-remitting demyelinating CNS disorder Although previously thought to be a variant of multiple sclerosis, it is now recognised to be a distinct disease, particularly prevalent in Asian populations1. It typically involves the optic nerves and cervical spine, with imaging of the brain frequently normal. Vomiting is also a common presenting complaint.
Diagnosis is requires bilateral optic neuritis, myelitis and 2 of the follow 3 criteria2:
- Spinal cord lesion involving 3 or more spinal levels
- Initially normal MRI brain
- Aquaporin 4 positive serum antibody
It’s features are best remembered by what they describe: the co-occurrence of optic neuritis and myelitis. Myelitis describes swelling of the spinal cord and in NMO it characteristically extends over three or more vertebral segments, and the limb features correspond to the level affected. The optic neuritis in NMO is bilateral.
The clinical course of NMO is variable. It may occur as a monophasic illness that is either fulminant and fatal or associated with varying degrees of recovery. Polyphasic courses characterised by relapses and remissions also occur.
A curative treatment for NMO does not exist to date and management, like in MS, focuses on remission and prevention of relapse.
Treatment of an acute attack is with steroids: 5 days of IV methylprednisolone at a dose of 1g, followed by an oral steroid taper. Maintenance therapy is normally with azathioprine, rituximab, or mycophenolate mofetil.
Neuromyelitis Optica - Example Question
Example Question:
A 45-year-old man complains of lower limb numbness associated with weakness. He also noted some recent problems with urinary incontinence and has recently attended the opticians due to some blurring of vision
On examination he has bilateral lower limb weakness (grade 3+/5). His tone was spastic on both sides with exaggerated reflexes. The planter reflexes were up-going bilaterally. The sensory level was at the tenth thoracic vertebra (T10). Eye examination revealed a normal visual acuity with a normal fundal examination.
He has a history of asthma and is currently well controlled with just a salbutamol inhaler.
Magnetic resonance imaging (MRI) of the brain is normal. MRI of the spine shows a hyper intense lesion spanning from (T7-T12). The following investigations had been ordered:
Na+ 135 mmol/l K+ 4 mmol/l Creatinine 80 µmol/l Urea 4.5 mmol/l CRP 5 mg/l ESR 10 mm/hr Urine analysis Normal ANA Negative
Which one of the following investigations would be most useful to reach a diagnosis?
Auditory evoked response potentials CSF analysis for oligoclonal bands > Anti-aquaporin 4 antibodies Serum B12 Visual evoked response potentials
Neuromyelitis Optica - Example Question
A 32-year-old lady develops a progressive loss of central vision in both eyes over two days. Her eyes are also painful to move. 24 hours later she develops additional paraesthesia in both arms with an associated weakness of both arms. On examination, she has central scotoma of both eyes. She also has a 3/5 global weakness of both arms with hyperreflexia and patchy sensory loss. In the following days, this progresses to paraesthesia and weakness in both lower limbs plus extensor plantar responses. Raised serum levels of which of the following would be most helpful in establishing the suspected underlying diagnosis? helpful in establishing the suspected diagnosis?
Anti-Hu antibodies Antinuclear antibodies N-methyl-d-aspartate (NMDA) receptor antibodies > Anti-Aquaporin-4 antibodies Voltage gated potassium channel antibodies
BILATERAL OPTIC NEURITIS, MYELITIS + VOMITING =
Neuromyelitis Optica (Devic’s Disease)
NMO - Example Question
A 37 year old Japanese female presents with her second episode of loss of colour vision and significant visual acuity impairment in both eyes. Three days later, she complains of vomiting, acute urinary retention, requiring urinary catheter insertion, and inability to move either leg. On examination, she was unable to correctly name any Ishihara plates. A MRI of her brain and spine demonstrates multiple hyperintense T2 white matter lesions in her spine suggestive of demyelination, one of which extends from C5 to T1. Which investigation confirms the diagnosis?
Lumbar puncture for oligoclonal bands Repeat MRI spine with diffusion weighting > Serum aquaporin 4 antibody Serum anti-NMDA antibody Repeat MRI spine with gadolinium contrast
The patient has presented with optic neuritis, myelitis and vomiting, strongly suggestive of a diagnosis of neuromyelitis optica (NMO), also known as Devics disease.
In this case CSF oligoclonocal bands neither confirms nor excludes a diagnosis MRI spine with DWI would demonstrate acute ischaemic infarcts if spinal stroke was suspected. Gadolinium enhanced imaging does not add to the diagnostic critiera for NMO. Anti-NMDA antibody is a serum autoantibody for a subtype of autoimmune encephalitis.
NB Diagnosis of NMO:
Diagnosis is requires bilateral optic neuritis, myelitis and 2 of the follow 3 criteria2:
1. Spinal cord lesion involving 3 or more spinal levels
2. Initially normal MRI brain
3. Aquaporin 4 positive serum antibody
Optic Neuritis presentation in NMO - Diagnosis: Example Question
A 32 year old female is referred for a neurological opinion. She describes two separate occasions within the last six months of unilateral blurred visual loss. Her symptoms developed over a few days, comprising blurring of the vision and pain, particularly on eye movement. On both occasions this peaked within three days then gradually resolved over two weeks. Lumbar puncture reveals elevated protein level and CSF pleocytosis. Serum Aquaporin-4 is positive. What is the most likely diagnosis?
Multiple sclerosis > Neuromyelitis optica Leptomeningeal gliomatosis Myasthenia gravis Idiopathic intracranial hypertension
Her symptoms are highly suggestive of Neuromyelitis optica (NMO, also known as Devic disease). NMO causes demyelination of the optic nerves or spinal cord due to autoimmune inflammation. Aquaporin-4 (AQP-4) is a water channel protein located in the astrocytic foot processes; NMO-IgG antibody attacks AQP-4 causing demyelination.
NMO typically presents with episodes of optic neuritis or transverse myelitis. The optic neuritis can be clinically indistinguishable from that seen in multiple sclerosis (MS), whereas the transverse myelitis is commonly more of a complete picture than that of MS. This is a result of the fact that the resulting spinal cord demyelination seen in NMO is longer and more extensive.
NMO - Example Question
A 60-year-old female presents to the Emergency Department with altered sensation in both hands and reduced visual acuity in the left eye. She states that these symptoms have slowly worsened over a week. She has no issues with bladder or bowel activity.
On examination, she is haemodynamically stable. Of note, she has a sensory loss throughout her arms and legs, but no clear sensory level. Additionally, she has brisk reflexes in both the upper and lower limbs. She also has a visual acuity of 6/36 in the left eye, but normal vision in the right eye, with normal visual fields.
Her MRI scan reveals multiple continuous segments of inflamed spinal cord throughout the cervical region and left optic nerve inflammation. There are no cerebral lesions. Her cerebrospinal fluid (CSF) studies are negative for oligoclonal bands.
Which of the following tests will confirm the diagnosis?
dsDNA antibodies > Aquaporin-4 antibodies ACh receptor antibodies NMDA receptor antibodies Neuronal antibodies
The description of a patient with optic neuritis and longitudinal extensive cervical transverse myelitis with a CSF negative for oligoclonal bands is highly suggestive of neuromyelitis optica (NMO). The classic antibody associated with this disease is NMO-IgG or antibodies against aquaporin-4.
The 2006 diagnostic criteria for NMO are as follows:
Transverse myelitis and optic neuritis with at least 2 of the following features:
MRI brain negative/nondiagnostic for multiple sclerosis
MRI spinal cord lesion extending over 3 vertebral segments (LETM)
NMO-IgG/Aquaporin-4 antibody seropositivity
NMO - Diagnostic Criteria
The 2006 diagnostic criteria for NMO are as follows:
Transverse myelitis and optic neuritis with at least 2 of the following features:
MRI brain negative/nondiagnostic for multiple sclerosis
MRI spinal cord lesion extending over 3 vertebral segments (LETM)
NMO-IgG/Aquaporin-4 antibody seropositivity
NMO - Example Question
A 46 year old white Caucasian female presents to the Emergency Department after waking up unable to walk and complains for problems with vision in her right eye. The patient says she is normally extremely healthy and the only time she has ever visited her GP was when she had an episode of diarrhoea and vomiting about a week ago. She is understandably distressed as she has not experienced any symptoms before and has not been previously diagnosed with any medical conditions. She has no drug or family history. Nursing staff report to you that she has been given a pad on her bed as she is incontinent of urine, which she is tearfully embarrassed by.
On examination of her cranial nerves, a right relative afferent papillary defect is noted. Visual acuity and colour vision are 6/6 with 17/17 Ishihara plates on the left, 6/60 with 0/17 Ishihara plates on the right. She reports no diplopia with a full range of eye movements and normal facial sensation. Facial movements are normal. Fundoscopy was unremarkable. Examination of the patients upper and lower limb power demonstrateted normal tone with 2-/5 power on the left arm and leg in all movements; and 4-/5 all movements in right arm and leg. There is patchy loss of sensation to cotton wool on right lateral wrist and anterior aspect left lateral shin. Both plantars are upgoing. Reflexes are brisk at knee and ankles bilaterally. Anal tone and saddle sensation are intact. The patients cognitive state is normal on superficial examination.
An urgent MRI head and whole spine demonstrates abnormal high signal in the cervical cord from C3 to C7. Her blood tests were mislabelled and hence unavailable. A lumbar puncture was performed with the following results:
WCC 12 mm/³ RBC <1 mm/³ Protein 0.9 g/l Glucose 5.2 mmol/l (10.2 mmol/l serum) Oligoclonal bands awaited Viral PCR awaited
What is the likely diagnosis?
Idiopathic intracranial hypertension Transverse myelitis Miller-Fisher syndrome Multiple sclerosis > Devic's disease
A first episode of a optic neuritis and myelitis occurring together is suggestive of a central neuroinflammatory cause. A full range of eye movements makes Miller-Fisher syndrome unlikely (and any ataxia demonstrated is likely secondary to limb weakness). Although there is the temptation of diagnosing multiple sclerosis in a patient with features disseminated in place, the keys to the answer are the sites of the lesion (optic nerve and cervical cord) and the long length of cord involvement beyond 3 vertebral levels, much more suggestive of neuromyelitis optic or Devic’s disease. The diagnosis would be clinched by a positive aquaporin 4 antibody.
Neuromyelitis Optica - Diagnosis
Diagnosis is requires bilateral optic neuritis, myelitis and 2 of the follow 3 criteria:
- Spinal cord lesion involving 3 or more spinal levels
- Initially normal MRI brain
- Aquaporin 4 positive serum antibody
However this says unilateral OR bilateral optic neuritis !
The 2006 diagnostic criteria for NMO are as follows:
Transverse myelitis and optic neuritis with at least 2 of the following features:
MRI brain negative/nondiagnostic for multiple sclerosis
MRI spinal cord lesion extending over 3 vertebral segments (LETM)
NMO-IgG/Aquaporin-4 antibody seropositivity
Neuromyelitis Optica - Mx
Curative treatment for NMO does not exist to date and management, like in MS, focuses on remission and prevention of relapse.
Treatment of an acute attack is with steroids: 5 days of IV methylprednisolone at a dose of 1g, followed by an oral steroid taper.
Maintenance therapy is normally with azathioprine, rituximab, or mycophenolate mofetil.
Differentiating Transverse Myelitis/ Neuromyelitis Optica/ Multiple Sclerosis
Transverse myelitis = inflammation of SC
Can be first symptom of either multiple sclerosis (MS) or neuromyelitis optica (NMO)!
NMO typically presents with episodes of optic neuritis or transverse myelitis. The optic neuritis can be clinically indistinguishable from that seen in multiple sclerosis (MS), whereas the transverse myelitis is commonly more of a complete picture than that of MS. This is a result of the fact that the resulting spinal cord demyelination seen in NMO is longer and more extensive.
MS Diagnosis - has to demonstrate lesions separate in time and space
Although there is the temptation of diagnosing multiple sclerosis in a patient with features disseminated in place the sites of the lesion (optic nerve and cervical cord) and the long length of cord involvement beyond 3 vertebral levels may be much more suggestive of neuromyelitis optic or Devic’s disease.
