A serum autoantibody marker of neuromyelitis optica : distinction from multiple sclerosis

Background: The authors previously proposed diagnostic criteria for neuromyelitis optica (NMO) that facilitate its distinction from prototypic multiple sclerosis (MS) However, some patients with otherwise typical NMO have additional symptoms not attributable to optic nerve or spinal cord inflammation or have MS-like brain MRI lesions Furthermore, some patients are misclassified as NMO by the authors’ earlier proposed criteria despite having a subsequent course indistinguishable from prototypic MS A serum autoantibody marker, NMO-IgG, is highly specific for NMO The authors propose revised NMO diagnostic criteria that incorporate NMO-IgG status Methods: Using final clinical diagnosis (NMO or MS) as the reference standard, the authors calculated sensitivity and specificity for each criterion and various combinations using a sample of 96 patients with NMO and 33 with MS The authors used likelihood ratios and logistic regression analysis to develop the most practical and informative diagnostic model Results: Fourteen patients with NMO (146%) had extra-optic-spinal CNS symptoms NMO-IgG seropositivity was 76% sensitive and 94% specific for NMO The best diagnostic combination was 99% sensitive and 90% specific for NMO and consisted of at least two of three elements: longitudinally extensive cord lesion, onset brain MRI nondiagnostic for MS, or NMO-IgG seropositivity Conclusions: The authors propose revised diagnostic criteria for definite neuromyelitis optica (NMO) that require optic neuritis, myelitis, and at least two of three supportive criteria: MRI evidence of a contiguous spinal cord lesion 3 or more segments in length, onset brain MRI nondiagnostic for multiple sclerosis, or NMO-IgG seropositivity CNS involvement beyond the optic nerves and spinal cord is compatible with NMO

https://n.neurology.org/content/neurology/66/10/1485.full.pdf

Revised diagnostic criteria for neuromyelitis optica

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serves as a specific marker for NMO. Here we show that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. NMO may represent the first example of a novel class of autoimmune channelopathy.

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IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel.

Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient's clinical deficits. We thus analysed global brain pathology in multiple sclerosis, focusing on the normal-appearing white matter (NAWM) and the cortex. Autopsy tissue from 52 multiple sclerosis patients (acute, relapsing-remitting, primary and secondary progressive multiple sclerosis) and from 30 controls was analysed using quantitative morphological techniques. New and active focal inflammatory demyelinating lesions in the white matter were mainly present in patients with acute and relapsing multiple sclerosis, while diffuse injury of the NAWM and cortical demyelination were characteristic hallmarks of primary and secondary progressive multiple sclerosis. Cortical demyelination and injury of the NAWM, reflected by diffuse axonal injury with profound microglia activation, occurred on the background of a global inflammatory response in the whole brain and meninges. There was only a marginal correlation between focal lesion load in the white matter and diffuse white matter injury, or cortical pathology, respectively. Our data suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter. With chronicity, diffuse inflammation accumulates throughout the whole brain, and is associated with slowly progressive axonal injury in the NAWM and cortical demyelination.

/pdf/cortical-demyelination-and-diffuse-white-matter-injury-in-2t65y6m2j8.pdf

Cortical demyelination and diffuse white matter injury in multiple sclerosis

Substantial advances have elucidated some of the central mechanisms underlying the inflammation, demyelination, and neurodegeneration that occur in multiple sclerosis Correspondingly, the clinical strategies available for the management of the disease have widened This review focuses on the current knowledge of the pathogenesis of the inflammatory and neurodegenerative elements of the multiple sclerosis plaque

Multiple Sclerosis — The Plaque and Its Pathogenesis

MS is a chronic recurrent inflammatory disorder of the CNS. The disease results in injury to the myelin sheaths, the oligodendrocytes, and, to a lesser extent, the axons and nerve cells themselves.1-5⇓⇓⇓⇓ The symptoms of MS vary, depending in part on the location of plaques within the CNS. Common symptoms include sensory disturbances in the limbs, optic nerve dysfunction, pyramidal tract dysfunction, bladder or bowel dysfunction, sexual dysfunction, ataxia, and diplopia.5 Four different clinical courses of MS have been defined.6 The first, relapsing–remitting MS (RRMS), is characterized by self-limited attacks of neurologic dysfunction. These attacks develop acutely, evolving over days to weeks. Over the next several weeks to months, most patients experience a recovery of function that is often (but not always) complete. Between attacks the patient is neurologically and symptomatically stable. The second clinical course, secondary progressive MS (SPMS), begins as RRMS, but at some point the attack rate is reduced and the course becomes characterized by a steady deterioration in function unrelated to acute attacks. The third clinical type, primary progressive MS (PPMS), is characterized by a steady decline in function from the beginning without acute attacks. The fourth type, progressive–relapsing MS (PRMS), also begins with a progressive course although these patients also experience occasional attacks.

Evaluation of the relative effectiveness of different therapies requires consideration of which outcome measure or measures are relevant to the goals of therapy. Clearly, the most important therapeutic aim of any disease-modifying treatment of MS is to prevent or postpone long-term disability. However, long-term disability in MS often evolves slowly over many years.1-3⇓⇓ Clinical trials, by contrast, study patients for only short periods of time (2 or 3 years) and, therefore, use only short-term outcome measures to assess efficacy. As a result, …

https://n.neurology.org/content/neurology/58/2/169.full.pdf

Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines.

G. P. Garmany

Papers

Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines.