Neuromyelitis Optica

Introduction[edit | edit source]

Devic.jpg

Neuromyelitis Optica (NMO) or Devic's Syndrome is a rare autoimmune disease of the Central Nervous System (CNS) that mainly affects the optic nerve (CN II), a paired nerve which conveys visual impulses to the lateral geniculate nucleus of the brain[1], and spinal cord. It's a demyelinating disorder thus myelin, an insulator of the CNS is the primary focus of the disease[2]. This condition affects more prevalent in women than men[3].

There are two types of NMO:

  • Relapsing form: This form is characterized by periodic flare-ups with some recovery and another surge later. 80% of affected patients are female.[3]
  • Monophasic form: This form is characterized by a single attack that lasts a month or two months. Men and women get this type equally[4].

Pathological Process[edit | edit source]

Neuromyelitis Optica is caused by a highly specific serum immunoglobulin (Ig)G autoantibody (NMO-IgG) which targets the most abundant astrocytic water channel aquaporin-4 (AQP4) causing the activation of other parts of the immune system and thus resulting in the inflammation and damage to cells as well as the demyelination of the optic nerve (optic neuritis) and the spinal cord (myelitis)[5] [3]. NMO-IgG/AQP4-antibodies are present in up to 80% of patients with NMO [6].

Clinical Presentation[edit | edit source]

Patients with NMO experience attacks that come and go. These attacks vary from mild to severe and can last from days to months ad in some cases these attacks may last and become permanent. The symptoms are broken down into three categories[7]:

Optic neuritis (ON) occurs due to the inflammation of one or both of the optic nerves. Some of the optic neuritis symptoms include[8]:

  • Decreased visual acuity
  • Visual field defects
  • Color blindness
  • Eye pain

Transverse Myelitis (TM) occur due to the inflammation of the spinal cord and some of it's symptoms include[9]:

  • Muscle weakness and paralysis
  • Decreased sensation
  • Incontinence
  • Spasticity
  • Pain
  • Sexual dysfunction

Brain function disruptions occur when NMO affects the brain stem and the hypothalamus which are the main centers that control the autonomic processes in the body. Some of its symptoms include[10]:

  • Uncontrollable hiccups
  • Pruritus
  • Nausea and vomiting
  • Diplopia and nystagmus
  • Palsy
  • Vertigo and ataxia
  • Trigeminal neuralgia

Diagnostic Procedures[edit | edit source]

The diagnostic criteria for Neuromyelitis Optica require the presence of history of optic neuritis and transverse myelitis in addition to 3 other supportive criteria which are[11]:

  • Magnetic Resonance Imaging (MRI) not diagnostic of Multiple Sclerosis (MS) at disease onset
  • Spinal MRI with a contiguous lesion ≥ 3 segments
  • Aquaporin-4 immunoglobulin G (AQP4-IgG) seropositivity (Blood Test)

In addition to that other findings which may raise suspicion of NMO include:

  • For ON, patients with severe vision loss or visual field depression and MRI findings of posterior optic nerve or chiasm involvement of extensive visual pathway lesions[12].
  • For TM, the presence of a longitudinally extensive spinal cord or central cord lesion. In addition to that, cerebrospinal fluid (CSF) findings suggestive of NMO presence include a pleocytosis greater than 50 cells per microliter, a high percentage of polymorphonuclear cells, or the presence of eosinophils[13].

Differential Diagnosis[edit | edit source]

The diagnosis of Neuromyelitis Optica is usually central to the presence of AQP4-Ab however clinical and radiological differential examinations remain important to rule out the possibility of other diseases that mimic the clinical and radiological features of NMO.

  • Multiple sclerosis (MS): MS and NMO share the same phenotypic features however they are very different in terms of epidemiology where MS is more common than NMO and there's high female predominance in NMO and moderate female predominance with MS[14]. In addition to that, they differ in terms of prognosis where the chance of having severe visual loss in the chronic state in NMO is common occurring in 50% of patients within 10 years of onset on the disease while in MS it is uncommon occurring in only 4.2% of patients within 11 years of onset of disease[15]. The differential diagnosis is critically important because the disease-modifying treatments used for MS such as interferon-β and fingolimod can aggravate NMO[7].
  • Acute Disseminated Encephalomyelitis (ADEM): ADEM differs from NMO by the absence of AQP4-Ab, the absence of female predominance, the presence of polyfocal neurologic symptoms at onset and it being more common among pediatric patients than older patients[16].
  • Idiopathic Acute Transverse Myelitis (iATM): Female gender, recurrent disease course, higher expanded disability status scale (EDSS), and poor response to steroid treatment are all associated with the presence of AQP4-Ab among patients with isolated longitudinally extensive transverse myelitis (LETM) which is frequently associated with NMO rather than iATM[17].

Management[edit | edit source]

There is no cure for Neuromyelitis Optica however with proper management various symptoms of the disease can be reversed, prevention of future attacks can be done and even long-term remission is possible.

Medical Management[edit | edit source]

Medical intervention upon diagnosis of NMO includes:

  • Intravenous Methylprednisolone Pulse Therapy (IVMP): Often used in early stages to manage acute exacerbations and minimize axonal loss during acute stages[18].
  • Therapeutic Plasma Exchange (TPE) : Often used when the treatment with corticosteroids does not improve the patient's condition or makes it worse. The use of TPE helped reduce the number of NMO exacerbations and provided sustained stabilization in patients with steroid-refractory relapsing forms of NMO[19].
  • Immunosuppressants like azathioprine[20] and mycophenolate[21].

Physiotherapy Management[edit | edit source]

Physiotherapy management is essential for possible future remission as interventions focus on the clinical presentations which are most of the time physical disabilities. Physiotherapy interventions may include[22][23]:

  1. Gait training
  2. Wheelchair training
  3. Neuromuscular and Muscular Electrical Stimulation (NMES)
  4. Transfer training
  5. Strengthening exercises
  6. Stretching exercises

References[edit | edit source]

  1. Smith AM, Czyz CN. Neuroanatomy, Cranial Nerve 2 (Optic). InStatPearls. StatPearls Publishing. 2022
  2. Kowarik MC, Soltys J. Bennett JL. The Treatment of Neuromyelitis Optica. Journal of Neuro-Ophthalmology. 2014. 34 (1): 70–82
  3. 3.0 3.1 3.2 Barkhof F, Koeller KK (February 2020). 13 Demyelinating Diseases of the CNS (Brain and Spine) . In: Hodler J, Kubik-Huch RA, von Schulthess GK (eds.). Diseases of the Brain, Head and Neck, Spine 2020–2023: Diagnostic Imaging . IDKD Springer Series. Cham, Switzerland: Springer. pp. 165–176.
  4. Neuromyelitis Optica. Neuromyelitis Optica | Johns Hopkins Medicine. Available at: https://www.hopkinsmedicine.org/health/conditions-and-diseases/neuromyelitis-optica (accessed 17/2/2023)
  5. Paul F, Jarius S, Aktas O, Bluthner M, Bauer O, Appelhans H, Franciotta D, Bergamaschi R, Littleton E, Palace J, Seelig HP. Antibody to aquaporin 4 in the diagnosis of neuromyelitis optica. PLoS medicine. 2007 Apr;4(4):e133.
  6. Waters P, Jarius S, Littleton E, Leite MI, Jacob S, Gray B, Geraldes R, Vale T, Jacob A, Palace J, Maxwell S. Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Archives of neurology. 2008 Jul 14;65(7):913-9.
  7. 7.0 7.1 Jarius S, Wildemann B, Paul F. Neuromyelitis optica: clinical features, immunopathogenesis and treatment. Clinical & Experimental Immunology. 2014 May;176(2):149-64.
  8. Toosy AT, Mason DF, Miller DH. Optic neuritis. The Lancet Neurology. 2014 Jan 1;13(1):83-99.
  9. Frohman EM, Wingerchuk DM. Transverse myelitis. New England Journal of Medicine. 2010 Aug 5;363(6):564-72.
  10. Cho EB, Han CE, Seo SW, Chin J, Shin JH, Cho HJ, Seok JM, Kim ST, Kim BJ, Na DL, Lee KH. White matter network disruption and cognitive dysfunction in neuromyelitis optica spectrum disorder. Frontiers in neurology. 2018 Dec 17;9:1104.
  11. Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised Diagnostic Criteria for Neuromyelitis Optica. Journal of Neurology. 2006. 66 (10): 1485–9.
  12. Fernandes DB, Ramos Rde I, Falcochio C, Apostolos-Pereira S, Callegaro D, Monteiro ML. Comparison of visual acuity and automated perimetry findings in patients with neuromyelitis optica or multiple sclerosis after single or multiple attacks of optic neuritis. J Neuroophthalmol. 2012;32:102–106.
  13. Jarius S, Paul F, Franciotta D, Ruprecht K, Ringelstein M, Bergamaschi R, Rommer P, Kleiter I, Stich O, Reuss R, Rauer S. Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures. Journal of the neurological sciences. 2011 Jul 15;306(1-2):82-90.
  14. Asgari N, Lillevang ST, Skejoe HP, Falah M, Stenager E, Kyvik KO. A population-based study of neuromyelitis optica in Caucasians. Neurology. 2011 May 3;76(18):1589-95.
  15. Merle H, Olindo S, Bonnan M, Donnio A, Richer R, Smadja D, Cabre P. Natural history of the visual impairment of relapsing neuromyelitis optica. Ophthalmology. 2007 Apr 1;114(4):810-5.
  16. Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, Ghezzi A, Hintzen R, Kornberg A, Pohl D, Rostasy K. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Multiple Sclerosis Journal. 2013 Sep;19(10):1261-7.
  17. Kim SM, Waters P, Woodhall M, Kim JY, Kim JE, Yang JW, Kim JS, Sung JJ, Park KS, Lee KW. Utility of aquaporin-4 antibody assay in patients with neuromyelitis optica spectrum disorders. Multiple Sclerosis Journal. 2013 Jul;19(8):1060-7.
  18. Nakamura M, Nakazawa T, Doi H, Hariya T, Omodaka K, Misu T, Takahashi T, Fujihara K, Nishida K. Early high-dose intravenous methylprednisolone is effective in preserving retinal nerve fiber layer thickness in patients with neuromyelitis optica. Graefe's Archive for Clinical and Experimental Ophthalmology. 2010 Dec;248:1777-85.
  19. Khatri BO, Kramer J, Dukic M, Palencia M, Verre W. Maintenance plasma exchange therapy for steroid‐refractory neuromyelitis optica. Journal of clinical apheresis. 2012;27(4):183-92.
  20. Mandler RN, Ahmed W, Dencoff JE. Devic's neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology. 1998 Oct 1;51(4):1219-20.
  21. Vodopivec I, Miloslavsky EM, Kotton CN, Cho TA. A neurologist's guide to safe use of immunomodulatory therapies. InSeminars in neurology 2014 Sep (Vol. 34, No. 04, pp. 467-478). Thieme Medical Publishers.
  22. Kelling H. Physical Therapy Management of Newly Diagnosed Neuromyelitis Optica: A Case Report (Doctoral dissertation, University of Iowa).
  23. Kim WB, Lee SY, Kim BR, Kim YJ. Rehabilitation of neuromyelitis optica: Two CARE-compliant case reports. Medicine. 2019 Oct;98(41).