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Other Central Nervous System Demyelinating Disorders


Neuromyelitis Optica (Devic Disease) and Neuromyelitis Optic Spectrum Disorder

Clinical Vignette

A 58-year-old woman was admitted to the hospital with a 5-day history of numbness and weakness in both lower extremities, a tight bandlike sensation across her chest associated with gait difficulties, and urinary urgency. The patient had similar but less severe symptoms 1 year prior that resolved within a few weeks. She did not seek medical attention at that time. In addition, she reported having an episode of left optic neuritis 3 years prior and since then has had extremely poor vision in that eye.

Her neuro exam was remarkable for an afferent defect on the left, a pale left disk, visual acuity of 20/200 on the left, and lower extremity weakness with a T4 sensory level in all modalities. The patient had magnetic resonance images (MRIs) of her brain and spine that showed central predominant intramedullary T2 hyperintense signal abnormality from C7 through T5-T6, with peripheral enhancement from T2 through T4 ( Fig. 40.1 ). Spinal fluid showed 8 white blood cells, 90% lymphocytes, protein of 55, and glucose of 71, with normal IGG index and no oligoclonal bands. She had positive aquaporin-4 in the blood and in the spinal fluid. Lyme, ACE, ANA screen, and HIV were negative. The patient was diagnosed as having neuromyelitis optic spectrum disorder with positive aquaporin-4 antibodies. She was treated with a 5-day course of 1000 mg of IV methylprednisolone with some improvement of her symptoms and subsequently placed on intravenous rituximab every 6 months without any recurrence of the neurologic symptoms.

Fig. 40.1, (A) Sagittal T2 MRI of the thoracic spinal cord showing extensive abnormal T2 hyperintense signal in the lower cervical and upper thoracic cord with more than three segments involved, characteristic of NMO. (B) Sagittal T1 Fat Sat postcontrast image demonstrating peripheral intramedullary enhancement from T2 through T4.

Comment: This is a typical clinical presentation and imaging studies in this 58-year-old woman presenting with a thoracic transverse myelitis with an extensive spinal cord lesion extending for more than three vertebral bodies. Of note, this patient had a prior episode of a severe optic neuritis that left her legally blind on the left as well as a prior demyelinating event involving her spinal cord the year before. A positive serum aquaporin-4 confirmed the diagnosis.

Neuromyelitis optica (NMO) is an inflammatory disorder causing severe damage to the myelin and axons of the central nervous system, affecting mostly the optic nerves and spinal cord. First described by E. Devic in 1894, NMO was initially thought to be a variant of multiple sclerosis. However, recent advances have shown that NMO has its own distinct clinical and immunologic characteristics. The discovery over a decade ago of pathogenic IGG antibodies in patients with NMO that specifically target aquaporin-4 (AQPR-4), a water channel protein located in the astrocytic foot processes, has allowed an easier distinction between the two clinical entities, supporting a humoral rather than a cell-mediated mechanism. Furthermore, the increase in specificity of the AQPR-4 antibody due to improved assays have expanded the clinical and radiologic spectrum of NMO, prompting the introduction in 2007 of the term neuromyelitis optic spectrum disorders (NMOSD) to include AQPR-4 antibody positive patients with limited or atypical forms of NMO.

Pathologically this syndrome is characterized by astrocytic damage, demyelination, neuronal loss, and frequently the presence of severe necrosis.

Revised criteria as of 2015 have simplified the terminology of these conditions, and currently the unifying term NMOSD stratified by presence, absence, or unknown status of AQPR-4 antibodies is recommended and will be used in this chapter. As expected, the criteria for patients with absent or unknown AQPR-4 antibodies are more stringent as compared with positive patients ( Box 40.1 ).

Box 40.1
Neuromyelitis Optic Spectrum Disorders Diagnostic Criteria for Adult Patients

Diagnostic criteria for NMOSD with AQP4 antibodies

  • 1

    At least one core clinical characteristic

  • 2

    Positive test for AQP4 antibodies using best available method (cell-based assay strongly recommended)

  • 3

    Exclusion of alternative diagnosis

Diagnosis criteria for NMOSD without or unknown AQP4 antibodies

  • 1

    At least two core clinical characteristics occurring as a result of one or more clinical attacks and meeting all the following requirements:

    • a

      At least one core clinical characteristic must be optic neuritis, acute myelitis with LETM, or area postrema syndrome

    • b

      Dissemination in space (two or more different core clinical characteristics)

    • c

      Fulfillment of additional MRI requirements, as applicable

  • 2

    Negative tests for AQP4 antibodies using best available detection method, or testing unavailable

  • 3

    Exclusion of alternative diagnosis

Core clinical characteristics

  • 1

    Optic neuritis

  • 2

    Acute myelitis

  • 3

    Area postrema syndrome episode of otherwise unexplained hiccups or nausea and vomiting

  • 4

    Acute brainstem syndrome

  • 5

    Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions

  • 6

    Symptomatic cerebral syndrome with NMOSD-typical brain lesions

Additional MRI requirements for NMOSD without or with unknown AQP4 antibodies

  • 1

    Acute optic neuritis: requires brain MRI showing:

    • a

      Normal findings or only nonspecific white matter lesions OR

    • b

      Optic nerve MRI with T2-hyperintense lesion or T1-W gado enhancing lesion extending over optic nerve length or involving optic chiasma

  • 2

    Acute myelitis requires

    • a

      Associated intramedullary MRI lesion extending over ≥3 contiguous segments (LETM) OR

    • b

      ≥3 contiguous segments of focal spinal cord atrophy in patients with history compatible with acute myelitis

  • 3

    Area postrema syndrome: requires associated dorsal medulla/area postrema lesions

  • 4

    Acute brainstem syndrome: requires associated periependymal brainstem lesions

AQP4, Aquaporin-4; LETM, longitudinal extensive transverse myelitis; MRI, magnetic resonance imaging; NMOSD, neuromyelitis optic spectrum disorders.

Clinical Picture

Since AQPR-4, the main target of the NMOSD IGG antibodies, is highly concentrated in the optic nerves, spinal cord gray matter, periaqueductal, and periventricular regions, the following clinical manifestations can occur in those patients: optic neuritis, acute myelitis, acute brainstem, and diencephalic syndromes and symptomatic cerebral syndrome. In general, NMOSD has a relapsing course with more than half of the patients presenting with a relapse within the first year of the initial attack and 90% within the first 3 years. In contrast to multiple sclerosis, secondary progression phase is rare in this entity.

Optic Neuritis

Episodes of optic neuritis in patients with NMOSD are characterized by visual loss often associated with eye pain, similar to the attacks secondary to multiple sclerosis; however, simultaneous or sequential involvement of both optic nerves, accompanied by severe visual loss, is characteristic of NMOSD. Altitudinal defects as well as involvement of the optic chiasm are also very suggestive of NMOSD.

Acute Myelitis

Differently from multiple sclerosis (MS), patients with NMOSD often present with a complete transverse myelitis characterized by motor and sensory loss below the level of the lesion associated with bowel and bladder dysfunction, as well as severe pain and paroxysmal tonic spasms of the trunk or extremities. In addition, in contrast to MS, the lesions in NMOSD are usually extensive, involving more than three vertebral segments on MRI.

Brainstem Syndrome

The most common brainstem syndrome is due to the involvement of the area postrema and characterized by nausea, vomiting, and intractable hiccups. Oculomotor involvement and less commonly involvement of other cranial nerves have been reported.

Acute Diencephalic Syndrome

Hypothalamic involvement may lead to hypersomnia or symptomatic narcolepsy as well as temperature and appetite dysregulations.

Symptomatic Cerebral Syndrome

Large tumefactive or spindlelike lesions causing encephalopathy and/or neurologic deficits have been reported in NMOSD.

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