Inflammatory demyelination disorders of the CNS are a broad group of disorders that involve acute on chronic autoimmune destruction CNS neuroglia. These are relatively common in Caucasians compared to Asian and African-American populations. These disorders vary in terms of their epidemiology, pattern of disease presentation, pathology, imaging findings and prognosis.
Multiple Sclerosis (MS):
MS is the most common form of chronic demyelinating diseases of the CNS.
It has a lifetime incidence of 0.1% and is more common among siblings of affected patients (up to 25%) indicating the strong genetic component of the disease.1,3 The central hypothesis surrounding the pathophysiology of MS involves dysregulation of CD4 T lymphocytes.
There is evidence to suggest that Th1 and Th17 lymphocytes are involved in autoimmunity resulting in demyelination.2 While the precise genes have not been identified, polymorphic variations of CD58, IL7R and IL2Ra genes were correlated with MS.
Over 90% of patients with MS are females and the most common age of onset is between 21 and 30 years. Presenting complaints often include ataxia, reduced visual acuity, parasthesias, bladder and bowel dysfunction and depression.
There are four major clinical courses of MS which include clinically isolated syndrome (CIS) and RIS, relapsing remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS). Patients with CIS may be diagnosed with MS if they satisfy the 2017 McDonald MS diagnostic criteria.
No single diagnostic marker is present and hence the diagnostic criteria is required to make a diagnosis of MS. The only laboratory finding that is part of the criteria is the presence of CSF-specific oligoclonal bands. On MRI, demyelinating plaques are typically identified in the juxtacortical, periventricular, cortical or infratentorial regions or in the spinal cord. Optic nerve involvement is common.4
Acute attacks are treated with intravenous methylprednisolone. Immunotherapies for relapsing and acute attacks include monoclonal antibody drugs, interferons and glatiramer acetate. Imaging is often used to assess response to treatment and monitor progression of disease.
There are many adverse effects of the treatment for MS. Some adverse effects include increased risk of miscarriage (interferon beta), Progressive Multifocal Leukoencephalopathy (PML) due to activation of JC virus (natalizumab), urinary tract infections (VLA4 antagonists), Therapy Related Acute Leukemia (TRAIL) (mitoxantorone), arrhythmias (fingolimod) and thyroid autoimmunity (alemtuzumab) to name a few.5
Neuromyelitis Optica Spectrum Disorders (NMOSD):
NMO or Aquaporin 4 IgG (AQP4-IgG) positive Neuromyelitis Optica was first described in 1870 and was thought to be a subtype of MS. It was later identified as a separate entity due to its unique antibody status. The pathogenesis involves autoimmunity against astrocytes.
Although it is more common in Caucasian populations overall, it has a higher prevalence than MS in non-Caucasian populations. NMO can also be encountered in patients less than 18 years of age.
Patients may present with vision loss, complete acute spinal cord syndrome, intractable hiccups, nausea, narcolepsy and autonomic regulation.
It commonly involves the optic nerve and circumventricular organs, or structures located around the third and fourth ventricles.
Acute attacks are treated with intravenous methylprednisolone. Immunosuppressive therapy with eculizumab has shown to slow disease progression.
There is stepwise progression of the disease due to accumulation of plaques.
Similar to MS, MRI can be used to assess response to treatment in NMO.6,7
Myelin Oligodendrocyte Glycoprotein (MOG) encephalomyelitis:
MOG was initially identified as a form of atypical NMO. These cases for NMO had similar phenotypes to NMO but were AQP4-IgG negative. Later MOG -IgG was identified in a subset of patients with NMOSD. Thus, they were grouped along with NMO Spectrum Disorder (NMOSD). Further testing revealed a significant number of patients with MOG-IgG with similar phenotypes, clinical course and prognosis. The pathogenesis involves autoimmunity against oligodendrocytes in contrast to astrocytes in NMO.
MOG is frequently seen in children, while the above mentioned disorders are less common.
Patients present with recurrent optic neuritis (ON), myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations.
Imaging plays a key role in identifying MOG because conventional treatments for MS and NMO are not effective in MOG-IgG disease.
Treatment of acute attacks involves IV methylprednisolone and IVIg. Immunosuppressive treatment is achieved best with rituximab, ocrelizumab and ofatumumab.
MOG disease also has a higher rate of relapse following cessation of steroid treatment for acute attacks.8,9,10
Mimics of Multiple Sclerosis:
Acute Disseminated Encephalomyelitis (ADEM):
ADEM is a rare inflammatory disorder of the CNS which often follows bacterial or viral infections and less commonly vaccination. It usually occurs in children and is MOG-IgG positive in about 50% of cases. ADEM has a lightly higher male preponderance compared to the above-mentioned disorders. Clinical presentation includes rapid onset altered level of consciousness, behavioral disturbance, ataxia, visual disturbance, seizures, focal neurological symptoms and nausea and vomiting. There is no unique antibody test associated with ADEM.
On MR, large lesions (>1 – 2 cm in size) are encountered in the supra and infratentorial white matter. Grey matter lesions include the basal ganglia and thalamus. Intramedullary lesions are seen in the spinal cord.
Treatment of acute attacks involves IV methylprednisolone. IVIg or plasmapheresis may be used if response to corticosteroids is not adequate. Long term immunomodulating drugs may not be necessary in most cases.
There is rapid partial resolution of the demyelinating lesions within 1-2 weeks. There may be a total resolution of symptoms and lesions in 6 – 12 months. Persistent neurological symptoms may be present in a small subset of people. For these patients, no therapy has been shown to be superior to another.11,12
Susac’s Syndrome (SS)
SS is a clinical disorder characterized by a triad of encephalopathy, sensorineural hearing loss and visual disturbance caused by branch retinal artery occlusion. The condition is very rare as there are only over 100 case reports for this disease. Although its pathophysiology is not clear, the occlusion is believed to be mediated by an autoimmune process affecting the small vessels. This is important to note as it is not a demyelinating disorder, however mimics demyelinating disorders.
It is commonly found in females between 20-40 years of age and quite often within the first year of pregnancy.
The clinical presentation includes symptoms like hearing loss, visual disturbance, urinary dysfunction, aphasia, cognitive impairment and headaches. Not all patients present with the triad described above. The MR findings of this disease are quite characteristic and are described below.
Treatment consists of initial high dose IV methylprednisolone followed by a course of tapering oral steroids. Cyclophosphamide has also shown some evidence of efficacy.
Over 50% of patients have irreversible damage and have residual symptoms, with a mild improvement seen in very few patients. Some patients may also relapse on treatment and may have further brain lesions despite therapy, indicating the need for further research into treatment for this disorder.16,17