Teaching Case

A previously healthy 35-year-old female patient presenting with a 2-week history of nausea and constipation, followed by fever, pruritus and difficulty walking in the week prior to admission.
Neurological examination revealed generalised weakness in all four limbs, most marked crural.

The initial head CT and MRI scans revealed a hypodense CT and a MR T2-weighted hyperintense diencephalic lesion, surrounding the third ventricle and involving hypothalamus. There is a T2-weighted hyperintense lesion involving the posterior medulla, and a longitudinally extensive spinal cord lesion extending from C4 to Th3. Both the brain and spinal cord lesions had no contrast enhancement.

Magnetic resonance imaging before and after 1 month of high-dose steroid treatment documented favourable evolution with significant decrease of the lesions sizes.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder, predominantly characterised by attacks of optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM). [1]
The discovery of disease-specific autoantibodies, aquaporin-4 immunoglobulin G (AQP4-IgG), changed the understanding of the disease, which has long been thought to be a variant of multiple sclerosis (MS). [2]

Diagnostic criteria for NMOSD are different depending on AQP4-IgG status. Patients with positive antibodies should have one core clinical characteristic, including clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. Diagnostic requirements are more stringent for seronegative patients and additional neuroimaging findings are needed. [3]

The patient met the diagnostic criteria for NMOSD, as the patient had at least one core clinical characteristic (acute myelitis), positive test for AQP4-IgG and alternative diagnoses were excluded. [3]

The most distinctive manifestations of NMOSD are ON and LETM. LETM is used to describe a spinal cord lesion that extends over 3 or more contiguous vertebral segments and that predominantly involves central grey matter. [2] LETM submitted to high-dose steroid treatment may on follow-up MRI progress into multiple shorter lesions, masking the correct diagnosis.

Brain MRI abnormalities are frequent in patients with NMOSD (43-70%), mostly represented by nonspecific punctate or patches of hyperintensities on T2-weighted sequences in the subcortical or deep white matter, but periventricular distribution is distinctive. Periependymal regions, the hypothalamus and the pathway between the third and fourth ventricles (known to have higher AQP4 expression) are believed to be highly characteristic for NMOSD. [4]

The major differential diagnosis includes: MS, ADEM, Neuro-Behçet, Neurosarcoidosis.
Unlike MS, myelitis in NMOSD is longitudinally and transversally extensive, the corpus callosum lesions involve mostly the splenium and there is a predilection for periventricular (namely III and IV ventricle) distribution.

In ADEM, the lesions are usually multiple, bilateral, synchronous and also can involve brain and spine. Deep and subcortical white matter and grey-matter lesions, such as thalami and basal ganglia may be seen. Spinal cord involvement is less common (33%) with a pattern similar to that of transverse myelitis. [4] Longitudinal MRI imaging could help distinguishing these pathologies, showing improvement or remission in ADEM, while frequently new lesions occur over time in MS and NMOSD. Neuro-Behçet typically involves brainstem and basal ganglia, with spinal cord involvement being less common.

Early and correct diagnosis is essential for proper treatment, preventing disability and avoiding initiation of some MS immunotherapies that may actually aggravate NMOSD. [3]

Written informed patient consent for publication has been obtained.