When the Central Nervous System Loses Color

History and Physical

A 14-year-old female presented with left arm and leg weakness. One year before, she recalled an episode of abnormal vision without diplopia, blurry vision, or color desaturation. These symptoms lasted for a month and self-resolved. Two weeks earlier, she had vertigo triggered by position changes or rapid head movements, and this also self-resolved. One week prior to presentation, she awoke with left arm and leg weakness that persisted. She denied numbness, trauma, recent infectious symptoms, neck stiffness, insect bites, incontinence, and recent travel. On physical exam, she was found to have intact ocular movements. Sensation was intact to light touch, proprioception, and pinprick throughout. Reflexes were 2+ and symmetric bilaterally. She was found to have grade 4/5 weakness throughout the left upper and lower extremities. Gait was slightly broad-based and unsteady.

Diagnostic Workup

MRI brain was significant for numerous periventricular and subcortical T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities ( Fig. 51.1A and B ). Lesions in the right precentral gyrus and superior frontal gyrus demonstrated incomplete ring and nodular enhancement, respectively ( Fig. 51.1C and D ). There was no restricted diffusion. The patient had extensive clinical workup ruling out infectious, metabolic, and rheumatologic etiologies, and tested negative for myelin oligodendrocyte glycoprotein (MOG) and aquaporin 4 (AQP4) antibodies. CSF studies were significant for lymphocyte predominant pleocytosis, elevated immunoglobin G (IgG) index, and >5 oligoclonal bands. She received 5 days of IV methylprednisolone with improvement and was started on disease-modifying therapy as an outpatient.

A panel of four axial magnetic resonance scan images shows multiple sclerosis with juxtacortical and periventricular hyperintensities and post-contrast enhancing lesions. — Fig. 51.1

Clinical Differential Diagnoses

Demyelinating diseases such as multiple sclerosis (MS), MOG-associated antibody disease (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD) are in the differential. Acute disseminated encephalomyelitis (ADEM) was not a consideration, given the lack of encephalopathy with any of the episodes.

Nondemyelinating neuroinflammatory conditions can also present with recurrent and subacute focal neurologic deficits.

Ischemic events, hemiplegic migraine, alternating hemiplegia of childhood, and periodic paralysis can present with acute-onset unilateral weakness. In this case, onset of symptoms was more subacute, recurrent, and varied, making these etiologies less likely.

Infectious processes can cause intra- and/or extra-parenchymal lesions with a subacute onset.

Imaging Differential Diagnoses

Periventricular and subcortical enhancing T2/FLAIR-hyperintense lesions can be seen in a variety of acquired demyelinating syndromes including MOGAD, NMOSD, and MS. On imaging, these disorders can overlap significantly, but there are some distinguishing features.

NMOSD is most likely to present with optic neuritis or myelitis. Brain lesions are typically hyperintense on T2/FLAIR imaging and can be asymmetric, distributed along the ventricles and cerebral aqueduct ( Fig. 51.2 ). Involvement of the area postrema in the caudal fourth ventricle is a more specific finding. NMOSD is often associated with AQP-4 antibodies, which bind water channels in areas with increased permeability of the blood-brain barrier. There may be contrast enhancement with a heterogeneous “cloud-like” or linear “pencil thin” appearance. When present, spinal lesions classically present as longitudinally extensive transverse myelitis (LETM), spanning three or more vertebral segments. Optic nerve lesions can also be longitudinally extensive and more often involve the chiasm.

A panel of two magnetic resonance scans shows hyperintense areas around the third ventricle and the left anterior temporal lobe. — Fig. 51.2

A similar imaging pattern can be found in patients with MOGAD. These patients tend to present with T2/FLAIR-hyperintense lesions of the deep gray matter, infratentorial parenchyma (brainstem, cerebellar peduncles), optic nerves and conus medullaris. However, these lesions are typically larger, more numerous, and poorly demarcated ( Fig. 51.3 ). The lesions may be symmetric, mimicking a leukodystrophy.