Neuromyelitis optica (NMO), also known as Devics disease or Devic's syndrome, is a rare type of autoimmune channelopathy associated with the antigen Aquaporin-4 water channel found in astrocytes which surround and protect the blood brain barrier in central nervous system (CNS). It causes inflammation and demyelination of the optic nerve and spinal cord.
Presentation
The signs and symptoms of NMO are that of optic neuritis or myelitis with anyone presenting initially.
Symptoms of optic neuritis:
- Loss of vision or loss of visual acuity in one eye (unilateral) or both the eyes (bilateral).
- Pain in the eye due to inflammation of the optic nerve.
- Loss of color vision.
- It may or may not precede an upper respiratory infection.
Symptoms of myelitis:
- It affects the spinal cord and causes demyelination of the spinal cord affecting bladder and below motor and sensory functions.
- Pain in spine or the extremities sometimes accompanied with stiff neck and headaches.
- Weakness in the limbs which may be mild or may progress to being as severe as paraplegia or quadriplegia.
- Loss of control over bowel and bladder.
- Loss of sensation or sensory impairment towards stimuli.
- Absent Deep tendon reflexes which may later become exaggerated.
As mentioned earlier MS and NMO are often confused together. Though both present similarly but NMO presents more severely than MS. MRI findings are normal in NMO unlike in MS and spinal tap does not show oligoclonal bands in NMO as compared to MS. NMO patients usually show improvement in vision and paralysis with high dose of corticosteroids with a partial recovery of the sensory and motor functions. Repeated attacks cause permanent damage leading to blindness or impaired mobility.
Entire Body System
- Arm Pain
Neuromyelitis optica may cause blindness in one or both eyes, weakness or paralysis in the legs or arms, painful spasms, loss of sensation, and bladder or bowel dysfunction from spinal cord damage. [delawareonline.com]
Common symptoms include: Blurry vision or blindness in one or both eyes Weakness or paralysis in the legs or arms Painful spasms Numbness or loss of sensation throughout the body Persistent nausea Uncontrollable vomiting Persistent hiccups Bladder or [ohsu.edu]
Neuromyelitis optica may cause blindness in one or both eyes, weakness or paralysis in the legs or arms, painful spasms, loss of sensation, uncontrollable vomiting and hiccups, and bladder or bowel dysfunction from spinal cord damage. [thailandmedical.news]
Respiratoric
- Pneumonia
This is the first report to describe the pathological findings of interstitial pneumonia, which may represent a rare extra-central nervous system complication of NMOSD. [ncbi.nlm.nih.gov]
Medical measures to prevent thromboembolic complications, aspiration pneumonia, decubiti and urinary tract infections are also required. 7 Links For further information on nmo please visit the worldwide devic's and nmo support group: [1] [flexikon.doccheck.com]
Side effects of this drug include life-threatening meningococcal meningitis, pneumonia, upper respiratory infections, and headache. Doctors usually give people who take eculizumab the meningococcal vaccine and closely monitor them. [msdmanuals.com]
- Common Cold
The most frequently reported adverse reactions reported by patients in the NMOSD clinical trial were: upper respiratory infection, common cold (nasopharyngitis), diarrhea, back pain, dizziness, influenza, joint pain (arthralgia), sore throat (pharyngitis [fda.gov]
The most common side effects in people with NMOSD treated with SOLIRIS include: common cold (upper respiratory infection) pain or swelling of your nose or throat (nasopharyngitis) diarrhea back pain dizziness flu like symptoms (influenza) including fever [alexion.com]
Unfortunately, it also can lower your immune system’s ability to fight contagious illnesses like the common cold, the flu, COVID-19, pneumonia and urinary tract infections (UTIs). [my.clevelandclinic.org]
Other preceding events included "common cold" and "feverish infection" (N = 10); sinusitis (2); otitis media (1); bronchitis (1); pneumonia (1); urinary tract infection (7; including urosepsis in 1); and gastrointestinal infection (2). [ncbi.nlm.nih.gov]
Gastrointestinal
- Constipation
Medications can help with issues such as constipation or frequent urination. Nerve pain: NMOSD attacks can cause long-term pain, numbness and other nerve issues. [ohsu.edu]
If the nerves to the bowels are affected, constipation results. Sexual function may be affected by numbness, erectile dysfunction or decreased lubrication. Optic nerve involvement results in decreased vision. [swedish.org]
[…] numbness, tingling, and a sensation of coldness or burning weak, heavy limbs, sometimes leading to total paralysis changes in urination patterns, including urinary incontinence, difficulty urinating, and more frequent urination fecal incontinence or constipation [medicalnewstoday.com]
- Persistent Vomiting
These problems were observed while the patient was hospitalized for a few days in the hepato-gastroenterology department for persistent vomiting, abdominal pain and hiccups lasting for about a month. [ncbi.nlm.nih.gov]
Ears
- Hearing Impairment
Steroid-responsive hearing impairment in NMO-IgG/aquaporin-4-antibody-positive neuromyelitis optica. J Neurol 2013;260:663-4. [PUBMED] 28. Jarius S, Paul F, Ruprecht K, Wildemann B. [annalsofian.org]
Steroid-responsive hearing impairment in NMO-IgG/aquaporin-4-antibody-positive neuromyelitis optica. J Neurology 2013 Feb;260(2):663-4. Jarius S, Paul F, Ruprecht K, Wildemann B. [klinikum.uni-heidelberg.de]
PubMed View Article Google Scholar Jarius S, Lauda F, Wildemann B, Tumani H: Steroid-responsive hearing impairment in NMO-IgG/aquaporin-4-antibody-positive neuromyelitis optica. J Neurol 2012. [doi.org]
Steroid-responsive hearing impairment in NMO-IgG/aquaporin-4-antibody-positive neuromyelitis optica. J Neurol. 2013; 260 :663–664. doi: 10.1007/s00415-012-6755-4. [ PubMed ] [ CrossRef ] [ Google Scholar ] 74. [ncbi.nlm.nih.gov]
Skin
- Pruritus
Neuromyelitis Optica as a Cause of Neuropathic Pruritus Neuropathic itch (or pruritus) refers to pruritus caused by neuronal or glial damage [5]. [karger.com]
Patients with NMOSD and PTS were characterized by a higher age at onset (P = 0.017), higher annual relapse rate (ARR) (P = 0.003), higher ARR of myelitis (P = 0.011), and a tendency to experience pruritus (P = 0.025). [ncbi.nlm.nih.gov]
Uncontrollable itching (pruritus). Nausea and vomiting that happen without a clear reason. Hearing loss. Double vision (diplopia), uncontrollable eye movements (nystagmus) or other problems with control of your eye movements. [my.clevelandclinic.org]
- Alopecia
Other cutaneous disorders, such as dermatomyositis, dermatitis herpetiformis, pemphigus foliaceus, psoriasis, bullous pemphigoid, pyoderma gangrenosum, vitiligo, atopic dermatitis, alopecia aerata, and limited scleroderma, have been reported to be associated [karger.com]
Acute toxicity gives rise to the well-known and expected side effects of alopecia, anaemia, thrombocytopaenia and leucopenia. Many patients also experience fever with or without bacteraemia. [doi.org]
- Sweating
Aquaporins are crucial for skin hydration, implicated in wound healing and epidermal barrier repair, and involved in sweat secretion and other physiological mechanisms [22]. [karger.com]
Examples include breathing, blood pressure, sweating and more. If NMO affects your brainstem, it can cause the following symptoms: Uncontrollable hiccups. Uncontrollable itching (pruritus). Nausea and vomiting that happen without a clear reason. [my.clevelandclinic.org]
- Skin Disease
Consequently, aquaporins may be involved in the pathophysiology of some skin diseases [23]. [karger.com]
- Dry Skin
skin, resistance to skin carcinogenesis, impaired cell proliferation, and altered fat metabolism [24]. [karger.com]
Eyes
- Eye Pain
Optic neuritis tends to occur suddenly and causes eye pain and varying degrees of vision loss. In most cases, only one eye is affected. [rarediseases.info.nih.gov]
pain Weakness, sensory changes, loss of bladder control, pain Diagnostic studies UMMC’s Center for Multiple Sclerosis Treatment and Research specializes in diagnosing, treating and managing NMOSD. [umms.org]
Symptoms of optic neuritis and transverse myelitis include: eye pain loss of vision colours appearing faded or less vivid weakness in the arms and legs pain in the arms or legs – described as sharp, burning, shooting or numbing – and increased sensitivity [nidirect.gov.uk]
During an NMOSD attack, or relapse, people with the condition might experience eye pain; vision loss; numbness, weakness, or paralysis in the arms and legs; and loss of bladder and bowel control. [nyulangone.org]
Individuals with NMOSD typically have attacks of optic neuritis, which causes eye pain and vision loss. [ajmc.com]
- Central Scotoma
Later, unilateral or bilateral ocular pain, acuity and color disturbances, phosphenes, as well as central scotomas start affect the patient secondary to the optic neuropathy. [6] There is no additional neurologic involvement aside of the spinal and ophthalmologic [eyewiki.aao.org]
Visual field testing typically reveals a central scotoma. Relative afferent pupillary dilation may be present, but can also be absent if both the optic nerves are affected equally. [one.wikia.com]
Neurologic
- Headache
TACs are a rare group of headache disorders characterized by severe unilateral headache in the V1 distribution of the trigeminal nerve and autonomic symptoms. This presentation in NMO is hitherto unreported in literature. [ncbi.nlm.nih.gov]
Call your doctor or get emergency medical care right away if you get any of these signs and symptoms of a meningococcal infection: headache with nausea or vomiting headache and fever headache with a stiff neck or stiff back fever fever and a rash confusion [alexion.com]
The prodrome consists of headache, fever, fatigue, myalgias and respiratory or gastrointestinal complaints. Rapid, bilateral and occasionally, complete visual loss. [flexikon.doccheck.com]
There is headache, vomiting, stiff neck, paralysis and blindness and the death rate is high. In those who survive, recovery is often surprisingly complete. Also known as Devic's disease. (Eugene Devic, 1858–1930, French physician). [medical-dictionary.thefreedictionary.com]
- Stroke
National Institute of Neurological Disorders and Stroke. 14 Feb. 2014. [medicinenet.com]
Neurological Disorders and Stroke » [brainfacts.org]
Her diagnosis was elusive, initially attributed to achalasia cardia and subsequently to stroke. A dorsal medullary lesion was revealed on MRI of the brain, which involved and extended beyond the area postrema. [ncbi.nlm.nih.gov]
- Limb Weakness
Late-onset biotinidase deficiency presents distinctly from the classical form such as limb weakness and vision problems. A 14-year-old boy presented with progressive vision loss and upper limb weakness. [ncbi.nlm.nih.gov]
Most individuals experience some degree of permanent limb weakness or vision loss from NMO. However, reducing the number of attacks with immunosuppressive medications may help prevent with accumulation of disability. [ninds.nih.gov]
Most individuals experience a moderate degree of permanent limb weakness from myelitis. Muscle weakness can cause breathing difficulties and may require the use of artificial ventilation. [medicinenet.com]
- Neuralgia
As patients with NMOSD experience severe occipital neuralgia, a relapse should be considered and a cervical MRI should be performed. [ncbi.nlm.nih.gov]
Less commonly brain stem lesions are present, resulting in; nausea, vomiting, vertigo, hypoacusia, trigeminal neuralgia, nystagmus, etc. [eyewiki.aao.org]
(progressive) (spinal cord) (subacute) G04.91 - see also Encephalitis ICD-10-CM Diagnosis Code G04.91 Myelitis, unspecified 2016 2017 2018 2019 Billable/Specific Code optic neuritis in G36.0 Neuritis (rheumatoid) M79.2 ICD-10-CM Diagnosis Code M79.2 Neuralgia [icd10data.com]
– oculomotor dysfunction, – deafness, – facial palsy, trigeminal neuralgia and other cranial nerve signs – vertigo. 18. • Other symptoms/syndromes that have been reported include – seizures, – hyposmia, – posterior reversible encephalopathy syndrome [de.slideshare.net]
- Vertigo
MS patients tend to have more symptoms like vertigo, facial pain, memory/cognitive problems, and mood problems because they have much more brain involvement, and MS may or may not include optic nerve or spinal cord involvement. [utswmed.org]
Other symptoms include vertigo, facial numbness, nystagmus, headache and postural tremor. 5 Diagnosis MRI of the brain and spinal cord : during acute optic neuritis the MRI may demonstrate a swelling of the affected optic nerve or the chiasm. [flexikon.doccheck.com]
Less commonly brain stem lesions are present, resulting in; nausea, vomiting, vertigo, hypoacusia, trigeminal neuralgia, nystagmus, etc. [eyewiki.aao.org]
Due to its effects on the brain, people with MS are more likely than people with NMO to have memory or cognitive problems, vertigo, facial pain, and mood changes. [medicalnewstoday.com]
If you also have other associated neurological problems, such as tinnitus or vertigo, it may indicate a problem with the nerves in the ear or brain. Hearing loss may be unilateral or bilateral. [en.wikipedia.org]
Workup
Diagnosis of NMO can be done as follows:
- MRI of the spine: It shows inflammation of the spinal cord extending more than 3 verterbral segments unlike MS in which only a short segment of spinal cord is affected [8].
- MRI of the brain: In NMO brain scans are normal or may show slight changes along with changes in optic nerve unlike MS.
- CSF analysis: It shows high number of white blood cells with preponderance of nuetrophils and no oligoclonal banding unlike MS.
- Blood test: A new test called as NMO Ig-G test or anti-aquaporin4 antibody test can be carried out. About 70% of patients test positive. This test is negative in MS and thereby marks a significant distinction.
EEG
- Abnormal Visual Evoked Potentials
[…] electro-oculogram[EOG]) 이상 망막전도(Abnormal electroretinogram[ERG]) 이상 시각 유발 전위(Abnormal visually evoked potential[VEP]) 신경자극에 대한 이상 반응(Abnormal response to nerve stimulation) R94.2 폐 기능 연구상 이상 결과(Abnormal results of pulmonary function studies) 감소된 환기용량 [dic.impact.pe.kr]
Microbiology
- Treponema Pallidum
Her series of blood test requests returned negative results for human immunodeficiency virus (HIV)1/2 testing and the treponema pallidum hemagglutination assay (TPHA)/Venereal Disease Research Laboratory test (VDRL) test for syphilis. [jmedicalcasereports.com]
Among bacterial infections, Mycobacterium tuberculosis, Mycoplasma pneumoniae, and Treponema pallidum have been reported in the literature [9, 26]. [karger.com]
• Treponema pallidum hemagglutination assay, • Paraneoplastic antibodies (in particular, anti-CV2/CRMP5 and anti-Hu). 30. [slideshare.net]
pallidum hemagglutination assay, and paraneoplastic antibodies (in particular, anti-CV2/CRMP5 [ 82 ] and anti-Hu). [link.springer.com]
Visual Field Test
- Central Scotoma
Later, unilateral or bilateral ocular pain, acuity and color disturbances, phosphenes, as well as central scotomas start affect the patient secondary to the optic neuropathy. [6] There is no additional neurologic involvement aside of the spinal and ophthalmologic [eyewiki.aao.org]
Visual field testing typically reveals a central scotoma. Relative afferent pupillary dilation may be present, but can also be absent if both the optic nerves are affected equally. [one.wikia.com]
Other Pathologies
- Spinal Cord Necrosis
[…] absence of oligoclonal bands Pathology: Spinal cord necrosis and cavitation with thickened vessel walls and absence of inflammatory infiltrates; demyelination of optic nerves with or without cavitation; no demyelinating lesions in the brain, brainstem [one.wikia.com]
Treatment
Treatment modality revolves around corticosteroids and plasmapheresis.
- Corticosteroids: In an acute attack; IV corticosteroids are beneficial.
- Plasmapheresis: Patients who did not respond to corticosteroids underwent a randomized, controlled crossover trial where they were treated with seven plamapheresis (1.0 to 1.5 plasma volume per exchange) for a period of 2 weeks and showed results. Another study carried out on 6 patients showed that about 50% of these patients responded to plasmapheresis [9]. Early initiation of plasmapheresis is recommended in cervical myelitis and optic neuritis [12]. Patients suffering from cervical myelitis are at a high risk of developing neurogenic respiratory failure and hence early intervention with plasmapheresis reduces the chances of it [10] [11].
Since MS and NMO were always considered to be one entity, it was believed that the immunomodulatory therapies of MS would help NMO patients. But recent studies have shown that they prove no benefit to the patient and are to be used only in cases of relapse [13].
Prognosis
The prognosis for neuromyelitis optica is not very promising and involves various factors especially number of relapses in initial years of the disease. Complete recovery is unlikely due to frequent relapses. Patients with relapses tend to have slow prognosis ranging from weeks to months. Frequent and severe relapses lead to early disability [5].
Approximately more than 50% of the patients suffering from neuromyelitis optica end up blind in one or both the eyes in just a span of 5 years posing the necessity of ambulatory help. The overall prognosis significantly depends on the severity of the first attach, the number of relapses during the first 2 years of the course of disease and presence of other autoimmune disorders like systemic lupus erythematosus (SLE) [6] [7].
Etiology
It isn't well understood as to why aquaporin-4 in CNS is attacked. NMO is known to being an autoimmune disease but in patients with non-relapsing variant, antibodies to myelin oligodendrocyte glycoprotein were discovered by researchers in the UK and Japan which shows immunological heterogenecity.
Nearly 50% of the patients show strong family history of autoimmunity. Though 95% of the patients have no family history of NMO but 3% of them have reported family history of other neurological condition.
Epidemiology
Though the incidence of NMO per 100,000 population ranges between 0.053 to 0.40, the prevalence per 100,000 population ranges 0.52 to 4.4 [3].
Pathophysiology
The most characteristic feature of NMO is the autoantibodies produced against aquaporin-4 (AQP4-Ab). The pathogenesis of NMO is based on in vivo and ex vivo experiments that were concluded as follows:
- Neuroinflammation: Direct attack on the astrocytes by AQP-4 Ab or activation of the complement system leading to attacking the astrocytes.
- Neuromodulation: Internalization of AQP-4Ab resulting in significant changes in astrocytes.
NMO AQP4-Ab possitive belong to a spectrum of autoimmune diseases of the CNS but with the recent discovery of AQP4-Ab autoimmunity; a new spectrum called the 'NMO spectrum disorder', 'aquaporinopathy' or 'autoimmune AQP4 channelopathy' was proposed. Despite of the recent advances, researchers havent been able to identify the pathogenesis behind AQP-4Ab seronegative patients thereby posing a challenge to treat such patients. Studies are also focusing on the T cell involvement in NMO patients. NMO was thought to be a subset of MS for a long time which is proven wrong now hence MS approved treatment modalities are condemned for NMO patients as they cause more harm than good.
According to prospective series and few retrospective studies, several treatment methods have proven effective in preventing an attack and stabilizing NMO patients while relapses were prevented by early intervention wtih immunosuppresants [4].
Prevention
Depending on the AQP4 antibody status, the prevention approach differs.
Postivie AQP4 antibody: Patients who are AQP4 antibody positive and fulfill the NMO criteria and have relapses would need immunosuppressive or immunomodulatory treatment to prevent further relapses.
Negative AQP4 antibody: Patients who have a negative AQP4 antibody and have had a single attack of LETM or ON don't need any preventive measure unless they have relapse. If relapse occurs, immunosuppression is the way to go to avoid further relapses.
Recurrent relapses increase the chances to keep a patient on immunosuppressive therapy risking long term side effects. Hence the goal in NMO is to achieve faster remission by tapering the dose of corticosteroids in a patient who responds well to them and help curb the side effects.
Summary
Neuromyelitis optica (NMO) is a rare autoimmune disease of the central nervous system (CNS) that presents classically with inflammation and demyelination of the optic nerve (optic neuritis) and spinal cord (transverse myelitis) [1] [2]. It is characterized by loss of vision and disturbed spinal function.
Visual pathway symptoms (Optic neuritis)
- Decreased or loss of vision in one or both the eyes.
- Pain in the eye worsening with movement.
- Loss of color vision or a 'washed out' appearence of the colors.
Spinal cord dysfunction (Longitudinally extensive transverse myelitis (LETM))
- Weakness in limbs which may further progress to paresis or quadriparesis.
- Decreased sensation to touch, heat, cold.
- Painful muscle spasm.
- Bladder incontinence.
Due to its striking similarity to multiple sclerosis (MS), NMO was considered to be a variant of multiple sclerosis and often was and is still misdiagnosed. The key features differing NMO from MS are as follows:
- In the early course of disease NMO does not involve the brain as compared to MS.
- The attacks seen in NMO are much worse than MS attack.
- NMO is known to be associated with a anti-aquaporin4 antibodies while MS is a T-cell mediated disease.
NMO is further divided into 2 main types:
- Relapsing neuromyelitis optica: This type of NMO is seen more in females than males. The first attack of NMO is followed by frequent attacks that occur over couple of years. Some patients may not recover completely that causes permanent neurological damage and hence causing disability.
- Monophasic neuromyelitis optica: It affects both males and females. The attacks are experienced just over few days or weeks with no relapsing attacks.
Diagnosis
Blood tests can detect anti-aquaporin-4 antibody (NMO-IgG). It is highly specific (>99%) but has a sensitivity of 48-72% depending on the assay used.
Treatment and prevention
For acute management of the disease, IV prednisolone and plasma exchange(PLEX) are considered. To prevent relapses-immusuppresants including mycophenolate mofetil or rituximab are considered along with rehabilitation.
Patient Information
Neuromyelitis optica (NMO) is a demyelinating disorder that affects the eyes and spinal cord. The underlying etiology is still unknown but its cause is often believed to be due to an autoimmune condition or post infection.
Causes
NMO is considered to be an autoimmune disease and has been associated with an abnormality in channelopathy. The presence of an antibody against the Aquaporin-4 is believed to cause the symptoms seen in NMO.
Symptoms
The symptoms are related to both eyes and the spinal cord.
Symptoms related to eye:
- Blurring of vision that could lead to complete loss of vision in one or both the eyes.
- Loss of color vision.
- Pain in eye movements.
Symptoms related to spinal cord:
Diagnosis
Diagnosis revolves around imaging studies and blood tests.
- Imaging studies: MRI of the brain and spinal cord are done to differentiate it from MS since they present in similar fashion.
- Visual evoked potential test is also used to diagnose NMO.
- Blood Test: AQP4 antibody also called as NMO-IgG is present in patients with NMO. Though in some patients it maybe negative but doesnt rule out NMO. Depending on the constellation of MRI findings and symptoms, a negative NMO-IgG patient can still have a diagnosis of NMO.
Treatment
Unfortunately till date no treatment exists. Various attempts are made to slow the progression of the disease and prevent relapses.
- Corticosteroids and immunomodulatory drugs: These have shown positive results and therefore Methylprednisolone and Azathioprine are used. Some studies have shown plasma exchange to be promising in patients refractory to corticosteroids.
- Other drugs: Rituximab (an anti–B-cell antibody) has shown to reduce the levels of IgG in the blood thereby reducing the symptom progression and severity.
- Drugs to relieve muscle spams: Drugs like Baclofen or tizanidine are used for their anti-spasmodic properties which helo in decreasing muscle spasms.
References
- Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients. J Neuroinflammation. 2012; 9:14.
- Wingerchuk DM, Lennon VA, Pittock SJ, et al. Revised diagnostic criteria for neuromyelitis optica. Neurology. 2006; 66:1485–89.
- Marrie RA, Gryba C. The incidence and prevalence of neuromyelitis optica: a systematic review. Int J MS Care. 2013; 15(3):113-8.
- Bernard-Valnet R, Marignier R. Evolution of Devic's neuromyelitis optica spectrum disorders. Presse Med. 2015 Apr; 44(4 Pt 1):401-10.
- Kantarci OH, Weinshenker BG. Natural history of multiple sclerosis. Neurol Clin. 2005; 23:17–38.
- Wingerchuk DM, Weinshenker BG. Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology. 2003; 60:848–53.
- Erb W. Über das Zusammenkommen von Neuritis optica und Myelitis subacute. Arch Psychiatr Nervenkr. 1879- 1880; 1:146-157.
- Filippi M, Rocca MA, Moiola L, et al. MRI and magnetization transfer imaging changes in the brain and cervical cord of patients with Devic's neuromyelitis optica. Neurology. 1999; 53:1705-1710.
- Watanabe S, Nakashima I, Misu T, et al. Therapeutic effi cacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica. Mult Scler. 2007; 13:128–32.
- Wingerchuk DM, Hogancamp WF, et al. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999; 53:1107–14.
- Keegan M, Pineda AA, McClelland RL, et al. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 2002; 58: 143–46.
- Ruprecht K, Klinker E, Dintelmann T, et al. Plasma exchange for severe optic neuritis: treatment of 10 patients. Neurology. 2004; 63:1081–83.
- Wingerchuk DM, Weinshenker BG. Neuromyelitis optica. Curr Treat Options Neurol. 2005; 7:173–82.