Other demyelinating diseases: inflammatory and compressive

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Other demyelinating diseases

inflammatory and compressive

Neuromyelitis optica, acute disseminated encephalomyelitis, and acute hemorrhagic leukoencephalopathy are covered in this chapter, together with a group of diseases in which demyelination is probably caused by compression. Demyelinating diseases that occur in other clinical contexts are included in the relevant chapters: progressive multifocal leukoencephalopathy in Chapter 14, central pontine myelinolysis and multifocal necrotizing leukoencephalopathy in Chapter 22, and Marchiafava Bignami disease in Chapter 25. The leukoencephalopathies associated with lysosomal and peroxisomal disorders are covered in Chapter 23.

NEUROMYELITIS OPTICA (DéVIC’S DISEASE)

Neuromyelitis optica (NMO) is characterized by the development of optic neuritis and acute transverse myelitis within weeks of each other (Table 20.1). Approximately two-thirds of patients present with visual loss and subsequently develop paraplegia, sensory loss, and loss of bladder and bowel control, but in the remaining third the order may be reversed. Unlike remissions in MS, recovery in NMO is usually incomplete, even from initial attacks. Some patients die during or soon after the acute syndrome, but others, although severely incapacitated, survive for many years.

Table 20.1

Criteria for diagnosis of neuromyelitis optica

Optic neuritis

Acute myelitis

At least two of the following three supportive criteria:

1. Contiguous spinal cord MRI lesion extending over ≥3 vertebral segments

2. Brain MRI not meeting diagnostic criteria for MS

3. NMO-Ig seropositive status (i.e. serum contains for aquaporin-4 antibodies)

Adapted from Wingerchuk DM, Lennon VA, Pittock SJ, et al. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006; 66:1485–1489.

MACROSCOPIC APPEARANCES

The optic nerves and affected region of the spinal cord are swollen and congested in patients who die during or soon after the acute presentation. The cord may appear necrotic on sectioning (Fig. 20.1). In patients who survive longer, the optic nerves become thin and gray-brown in color, while the cord shows similar discoloration (Fig. 20.2) and may be atrophic.

20.1 Acute neuromyelitis optica. Extensive softening of the spinal white matter and necrosis of the gray matter can be seen. The thoracic region (center section) is most severely affected.

20.2 Neuromyelitis optica. Brown discoloration of the upper part of the cervical cord in long-term survivor of neuromyelitis optica.

AQUAPORIN-4 ANTIBODIES AND NMO-SPECTRUM DISORDERS

The aquaporin-4 (AQP4) protein is a channel that controls the passage of water across the plasmalemma of certain types of cell. In the CNS, it is highly expressed in astrocytic endfeet around blood vessels and in circumventricular organs (e.g. the subforniceal organ and area postrema), and in certain subpopulations of ependymal cells (e.g. those covering the subforniceal organ).

Within these cells, AQP4 is complexed with the Na+-dependent excitatory amino acid transporter 2 (EAAT2); loss of AQP4 in NMO is associated with loss of EAAT2 as well.

AQP4-specific IgG is detectable in the serum of 60–90% of patients with NMO.

AQP4 autoimmunity is also found in a spectrum of CNS inflammatory demyelinating disorders (NMO-spectrum disorders) in patients who do not fulfil current criteria for a diagnosis of NMO but may have AQP4 antibody-associated foci of demyelination in the brain, particularly in AQP4-rich regions (e.g. the hypothalamus and periaqueductal region).

The prevalence of AQP4 autoimmunity is increased in patients with several other autoimmune diseases, such as myasthenia gravis, Graves disease, Hashimoto’s thyroiditis, systemic lupus erythematosus, and Sjögren syndrome).

MICROSCOPIC APPEARANCES

The optic nerves and spinal cord show extensive demyelination (Fig. 20.3). In the acute phase, involved segments of the spinal cord and optic nerve are inflamed, and the cord in particular may be partly necrotic (Fig. 20.4); the inflammatory infiltrates include perivascular neutrophils and eosinophils, and relatively few T cells. There tends to be pronounced perivascular deposition of immunoglobulins (particularly IgM) and C9neo (activated complement), and hyaline fibrosis of small blood vessels. Immunohistochemistry can also be used to demonstrate loss of AQP4 and EEAT2 in the demyelinated regions. The lesions become cavitated and gliotic in those patients who survive the acute stage, and there is usually associated degeneration of ascending and descending tracts.