The signs and symptoms of NMO are that of optic neuritis or myelitis with anyone presenting initially. 

Symptoms of optic neuritis:

1. Loss of vision or loss of visual acuity in one eye (unilateral) or both the eyes (bilateral).
2. Pain in the eye due to inflammation of the optic nerve.
3. Loss of color vision.
4. It may or may not precede an upper respiratory infection.

Symptoms of myelitis:

1. It affects the spinal cord and causes demyelination of the spinal cord affecting bladder and below motor and sensory functions.
2. Pain in spine or the extremities sometimes accompanied with stiff neck and headaches.
3. Weakness in the limbs which may be mild or may progress to being as severe as paraplegia or quadriplegia.
4. Loss of control over bowel and bladder.
5. Loss of sensation or sensory impairment towards stimuli.
6. 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.

• Underweight

  Alphabet (GOOG, GOOGL), Facebook (FB), and Amazon.com (AMZN) were initiated with an Overweight at Barclays, while Snap (SNAP) was initiated with an Equal Weight and Twitter (TWTR) was initiated with an Underweight. [thefly.com]

• Malaise

  […] warned to report immediately any signs or symptoms of bone marrow suppression e.g. inexplicable bruising or bleeding, infection Contra-indications: hypersensitivity to azathioprine or mercaptopurine Side-effects: hypersensitivity reactions (including malaise [web.archive.org]

• Back Pain

  If the swelling is in the lower back, then symptoms can include back pain, weakness of both legs and bowel and bladder problems. [gosh.nhs.uk]

  Six months before admission, he developed the lower back pain and numbness in lower limbs, and urinary incontinence. This time, he complained of acute onset of right lower limb paralysis, paresthesia and urinary incontinence. [ncbi.nlm.nih.gov]

  The most common adverse effects reported in the study that were associated with eculizumab were upper respiratory tract infection (29%), nasopharyngitis (21%), diarrhea (16%), back pain (15%), and dizziness (15%). [pharmacytimes.com]

• 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]

• Diplopia

  A 21-year-old female manifested dizziness and diplopia ten months and six months before, respectively. Both responded to steroid therapy and improved completely. [ncbi.nlm.nih.gov]

  LETM 40% Recurrent Optic Neuritis 20% Single Occurrence of Optic Neuritis Intractable Vomiting Acute Disseminated Encephalomyelitis (ADEM), Posterior Reversible Encephalopathy Syndrome (PRES) Encephalopathy, Sleep Disorder, SIAD Hearing Loss Ataxia, Diplopia [mayomedicallaboratories.com]

  Optic Neuritis 20% Single Occurrence of Optic Neuritis <5% Intractable Vomiting <5% Acute Disseminated Encephalomyelitis (ADEM), Posterior Reversible Encephalopathy Syndrome (PRES) <5% Encephalopathy, Sleep Disorder, SIAD <5% Hearing Loss <5% Ataxia, Diplopia [mayocliniclabs.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]

• 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]

• Nystagmus

  Rochester, MN Areas of focus: Cataract surgery, Temporal artery biopsy, Double vision, Ischemic optic neuropathy, Neuromyelitis optica, Nystagmus, Optic neuritis, Pituitary tumor, Pseudotumor cerebri more see full list in profile Eoin P. [mayoclinic.org]

  The examination confirmed left hemibody ataxia with nystagmus when looking to the left, pronounced left osteotendinous reflexes, and left hemibody hypoesthesia up to the base of the neck. [ncbi.nlm.nih.gov]

  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]

  Recently, cortical oscillopsia without nystagmus-related cortical involvement of area V5 in a patient with AQP4-Ab-seropositive NMOSD was reported [52]. 3.7. [hindawi.com]

• Lhermitte Sign

  Two months from the onset of digestive problems with Lhermitte's sign and hand and foot contracture access without vesico-sphincter problems were established. [ncbi.nlm.nih.gov]

  About 30% of the patients have a positive Lhermitte’s sign in patients with recurrent disease. [6] Signs and symptoms Approximately 30% of the patients present with a flu-like illness with symptoms such as; fever, myalgia, and headache. [eyewiki.aao.org]

  Lhermitte’s sign was absent in this patient. His gait, however, was unsteady. Full blood count showed haemoglobin 14.1 g/dl, white blood cells 11,900/mm3 (neutrophils 76%, lymphocytes 22%, monocytes 1%, and basophils 1%), and platelets 152,000/mm3. [hindawi.com]

  Devic 8 (little is written about Devic. 8 He also described ‘Lhermitte's sign’ in MS some 6 years before Lhermitte (Bereil T, Devic E. Sur un cas de douleurs à type de décharge dans la sclérose en plaques. [doi.org]

  Devic8 (little is written about Devic.8 He also described ‘Lhermitte's sign’ in MS some 6 years before Lhermitte (Bereil T, Devic E. Sur un cas de douleurs à type de décharge dans la sclérose en plaques. [nature.com]

• Dysarthria

  A 33-year-old man presented with dysarthria, movement disorder and occasional seizures. He had 6 relapses in 28 years. When suffered from upper respiratory tract syndrome, he developed behavioral and consciousness impairment. Cranial MRI was normal. [ncbi.nlm.nih.gov]

  Eight of them (53%) presented with encephalopathy, as evidenced by symptoms such as decreased mental status, confusion, and seizure, with or without other neurological symptoms such as dysarthria or hemiparesis. [hindawi.com]

  Paroxysmal dysarthria and ataxia in a patient with Behçet's disease. Journal of Neurology 1995; 242: 344-347. 3. Akman-Demir G, Bahar S, Baykan-Kurt B, Gürvit H, Serdaroğlu P. Intracranial hypertension in Behçet's disease. [florence.com.tr]

  A and B, FLAIR MR imaging shows hypothalamic and medullary lesions in symptomatic AQP4-positive NMO spectrum disorder presenting with diplopia, dysarthria, dysphagia, and a right-sided sensorimotor syndrome. [ajnr.org]

• Paresthesia

  This time, he complained of acute onset of right lower limb paralysis, paresthesia and urinary incontinence. [ncbi.nlm.nih.gov]

  In addition, there can be altered sensation (paresthesias). This altered sensation could include tingling, pins and needles, burning, coldness, pain or other odd sensations. [swedish.org]

  The common reactions include hypotension, vasovagal reactions, and perioral paresthesias due to hypocalcaemia. [emjreviews.com]

  Symptomatic therapy for pain, paresthesia, spasticity, dysuria and constipation which commonly occur in the chronic stage of NMO is also important to improve patients' quality of life. 収録刊行物 日本臨床免疫学会会誌 = Japanese journal of clinical immunology [ci.nii.ac.jp]

Diagnosis of NMO can be done as follows:

1. 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].
2. MRI of the brain: In NMO brain scans are normal or may show slight changes along with changes in optic nerve unlike MS.
3. CSF analysis: It shows high number of white blood cells with preponderance of nuetrophils and no oligoclonal banding unlike MS.
4. 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.

• Abnormal Visual Evoked Potential

  […] 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]

• 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]

• 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]

• Gliosis

  In active multiple sclerosis (MS) lesions astrocytes reveal changes of reactive protoplasmatic or fibrillary gliosis. [ncbi.nlm.nih.gov]

  Vascular hyalinization, tissue necrosis, demyelination, and gliosis commonly accompany the inflammatory process [18–22]. 3. Immunotherapy of NMO Immunotherapy of NMO is based on the current understanding of its pathogenesis. [hindawi.com]

  T2W image of brain showing a tumefactive demyelinating lesion with evidence of contralateral gliosis and atrophy from a previous attack. 3. PRES like brain lesions. 4. Lesion near fourth ventricle extending to middle cerebellar peduncle. 5. [annalsofian.org]

• HLA-A3

  Initial studies, using serological techniques, showed an association of MS with human leukocyte antigens (HLA) class I, especially HLA-A3 and HLA-B7.[1] Multiple recent researches which used current molecular methods [sequence specific oligonucleotide-polymerase [oaepublish.com]

• HLA-A1

  *03 and especially the whole haplotype, HLA A1-B8-DR3-DQ2, is the most commonly attributed to MG in the Caucasians, an haplotype common and in other autoimmune diseases.[32] HLA-DRB1*03 allele is highly frequent in the NMO-IgG positive patients, as we [oaepublish.com]

Treatment modality revolves around corticosteroids and plasmapheresis.

1. Corticosteroids: In an acute attack; IV corticosteroids are beneficial.
2. 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].

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].

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.

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].

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:

1. Neuroinflammation: Direct attack on the astrocytes by AQP-4 Ab or activation of the complement system leading to attacking the astrocytes.
2. 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].

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.

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:

1. 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. 
2. 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.

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:

1. Blurring of vision that could lead to complete loss of vision in one or both the eyes.
2. Loss of color vision.
3. Pain in eye movements.

Symptoms related to spinal cord:

1. Weakness in limbs.
2. Issues with bladder and bowel control.

Diagnosis

Diagnosis revolves around imaging studies and blood tests.

1. Imaging studies: MRI of the brain and spinal cord are done to differentiate it from MS since they present in similar fashion.
2. Visual evoked potential test is also used to diagnose NMO.
3. 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.

1. 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.
2. 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.
3. Drugs to relieve muscle spams: Drugs like Baclofen or tizanidine are used for their anti-spasmodic properties which helo in decreasing muscle spasms.

1. 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.
2.  Wingerchuk DM, Lennon VA, Pittock SJ, et al. Revised diagnostic criteria for neuromyelitis optica. Neurology. 2006; 66:1485–89.
3. Marrie RA, Gryba C. The incidence and prevalence of neuromyelitis optica: a systematic review. Int J MS Care. 2013; 15(3):113-8.
4. Bernard-Valnet R, Marignier R. Evolution of Devic's neuromyelitis optica spectrum disorders. Presse Med. 2015 Apr; 44(4 Pt 1):401-10.
5. Kantarci OH, Weinshenker BG. Natural history of multiple sclerosis. Neurol Clin. 2005; 23:17–38.
6. Wingerchuk DM, Weinshenker BG. Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology. 2003; 60:848–53.
7. Erb W. Über das Zusammenkommen von Neuritis optica und Myelitis subacute. Arch Psychiatr Nervenkr. 1879- 1880; 1:146-157.
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10. Wingerchuk DM, Hogancamp WF, et al. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999; 53:1107–14.
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