11th August 2024

Neuroinflammatory disorders

Neuromyelitis optica spectrum disorder

Previously known as Devic disease, neuromyelitis optica (spectrum disorder) (NMO)(SD) presents with recurrent episodes of unilateral or bilateral optic neuritis associated with myelopathy.

It is caused by an immune-mediated attack on aquaporin 4 (AQP4), which is a neural channel protein. NMO-IgG antibody selectively binds AQP4 causing demyelination and axonal death.

Symptoms caused by optic neuritis include:

• Loss or blurring of vision; NMOSD often affects both eyes, unlike MS
• Eye pain with movement
• Loss of colour vision

Symptoms caused by transverse myelitis include:

• Loss of bowel or bladder control or urinary retention
• Spasticity (increased muscle tone or stiffness in the arms or legs)
• Weakness, numbness, or loss of sensation

Blood testing for the AQP4 antibody is highly specific (>99%) and its sensitivity ranges from 48-87%.

Treatments consist of IV corticosteroids and plasma exchange. Immunosuppressive drugs such as mycophenolate mofetil, rituximab, and azathioprine have also been found to be beneficial in treatment. MS treatment is often ineffective in NMO.

Transverse myelitis

This describes inflammation of both sides of a section of the spinal cord due to damage to the myelin sheath.

Symptoms include:

• Pain
• Sensory loss in upper and lower limbs
• Motor weakness in upper and lower limbs
• Bladder and bowel dysfunction

Various conditions can cause transverse myelitis:

• Immune disorders such as MS, NMO, and post-infectious or post-vaccine autoimmune phenomena.
  Myelin oligodendrocyte glycoprotein (MOG) antibody associated disease (MOGAD) causing autoimmune demyelination of the CNS, in particular the optic nerves, brain and spinal cord, can also cause transverse myelitis. Anti-MOG antibodies are present in cases of MOGAD
• Viral infections, including herpes simplex, varicella zoster, cytomegalovirus, Epstein-Barr virus, hepatitis B, mumps, measles, and rubella
• Bacterial infections such as syphilis, TB, actinomyces, pertussis, tetanus, diphtheria, and Lyme disease
• Fungal infections including aspergillus
• Parasites, including toxoplasmosis, cysticercosis, and schistosomiasis
• Inflammatory disorders, such as sarcoidosis, systemic lupus erythematosus, Sjögren’s syndrome, mixed connective tissue disease, scleroderma, and Beçhet’s syndrome

Image Source: Wikimedia Commons (2010). Transverse_myelitis_MRI, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Transverse_myelitis_MRI.jpg (Accessed: 17 July 2024)

Transverse myelitis is diagnosed by MRI of the spinal cord, which confirms the presence of a lesion. An MRI brain may provide clues to underlying causes, especially MS.

Blood tests may be performed to rule out differentials and identify the cause of transverse myelitis, including the presence of autoantibodies (anti-AQP4, anti-myelin oligodendrocyte) and paraneoplastic antibodies. CSF analysis often shows elevated protein and leukocytes.

Management depends on the cause.

Autoimmune encephalitis

Autoimmune encephalitis comprises a group of non-infectious immune-mediated inflammatory disorders of the brain involving the cortical deep grey matter, with or without involvement of white matter, meninges, or spinal cord.

• Common causes of autoimmune encephalitis include acute disseminated encephalomyelitis (ADEM) and anti-NMDA (N-methyl-D-aspartate) receptor encephalitis.
• Paraneoplastic encephalitis is seen most with small cell lung, breast, ovarian and testicular cancer, and Hodgkin’s lymphoma. Antineoplastic antibodies (Anti-Hu, Yo, Ri and Ma) are often positive.
• MRI may often be normal in autoimmune encephalitis therefore, diagnosis is made by CSF analysis including analysis for CSF antibodies.