- The MRI can be used to meet the dissemination in space requirement if the McDonald criteria for a positive MRI are applied. The MRI must show three of the following four features: (1) nine or more white matter lesions or one gadolinium-enhancing lesion, (2) three or more periventricular lesions, (3) a juxtacortical lesion, (4) an infratentorial lesion.
- The combination of an abnormal CSF finding and two lesions on the MRI, of which one must be in brain, can also meet the dissemination in space criteria; the CSF must show either oligoclonal bands or an elevated lgG index.
- MRI can be used to satisfy criteria for dissemination in time after the initial clinical event, even in the absence of a new clinical demyelinating event; abnormal T2 or gadolinium-enhancing lesions must develop 3 months after the initial clinical event.
- An episode consistent with the clinical features of ADEM cannot be considered as a first event of multiple sclerosis in most circumstances.
Clinically isolated syndrome
CIS is defined as a first acute clinical episode of CNS symptoms with a presumed inflammatory demyelinating cause for which there is no prior history of a demyelinating event. This clinical event may be either monofocal or multifocal, but usually does not include encephalopathy (except in cases of brainstem syndromes). Examples include, but are not limited to, the following:
- optic neuritis (unilateral or bilateral)
- transverse myelitis (typically partial)
- brainstem, cerebellar and/or hemispheric dysfunction.
In each of these situations testing for increased antibody to NMO (NMO-IgG) and aquaporin protein 4 (AQP4), is indicated.
Aquaporin-4 (AQP4) autoimmunity
AQP4 is a water channel that is localized, appropriately, at CSF-brain junctions. It is thus expressed throughout the linings of the CSF compartment, notably in periventricular regions, on the pia, in the Virchow-Robin spaces, and of course in relation to the optic nerves and spinal cord. Antibodies to AQP4 are known both as AQP4-IgG and as NMO-IgG, and were originally decribed in adults specifically with neuromyelitis optica. AQP4 autoimmunity in children (mainly non-Caucasian and mainly girls) seems to be more pleomorphic, with brainstem (including ophthalmoparesis, cerebellar ataxia, intractable vomiting and hiccups) and encephalopathic presentations, but so far almost all develop recurrent optic neuritis and/or transverse myelitis.
CNS MRI shows increased T2 signal in areas predicted from the expression of AQP4, especially in periventricular sites (in descending order of frequency the medulla, supratentorial and infratentorial white matter, midbrain, cerebellum, thalamus, and hypothalamus), and as tentacle-like lesions in the central white matter along the course of the Virchow-Robin spaces.
Testing for AQP4-IgG/NMO-lgC. is becoming readily available, and should be considered in ADEM, CIS and multiple sclerosis when clinical and MRI features are consistent.
Mary D. King, 2009. A Handbook of Neurological Investigations in Children. 1 Edition. Mac Keith Press.