Paraneoplastic and Other Autoimmune Disorders of the Central Nervous System

Abstract

As a result of the burgeoning growth of disease-specific neural autoantibody markers available for diagnostic patient evaluation, there has been increasing awareness of autoimmune central nervous system (CNS) disorders in hospital practice. Hospital-based neurologists have also taken great interest in these disorders since many occur in the setting of an occult systemic cancer which can be detected and treated at an early stage, and many affected patients are responsive to immunotherapy. Associated neurological disorders are typically subacute in onset, some are common or classic (eg, limbic encephalitis, cerebellar degeneration), but others have atypical or multifocal presentations. For patients with a suspected paraneoplastic disorder, many and costly oncological evaluations may be required for diagnosis. Comprehensive serological and cerebrospinal fluid (CSF) evaluation for neural autoantibodies may permit a focused cancer evaluation (eg, antineuronal nuclear antibody type 1 [ANNA-1] is associated with small cell lung carcinoma), and in some circumstances may indicate the likelihood of a good response to therapy (eg, voltagegated potassium channel complex antibody) or poor neurological prognosis (eg, purkinje cell cytoplasmic antibody type 1 [antiYo]). Positron-emission tomography-computed tomography (PET-CT) imaging of trunk may increase the diagnostic yield for certain cancers where other modalities have been negative. For some patients, rapid treatment with immunotherapy may facilitate marked improvement, or full recovery; multiple sequential trials of one or more of steroids, intravenous immunoglobulin or plasma exchange, or combination therapy are often required. For patients with N-methyl-D-aspartate receptor antibody encephalitis, early treatment with immunosuppressants and weeks or months of supportive intensive care may additionally be required. One or more of clinical examination, electroencephalogram (including video telemetry), and imaging provide objective parameters to which posttreatment outcomes can be compared.

A practical approach to the diagnosis of spinal cord lesions

“…Up to 81% of patients have an associated antibody, most commonly collapsin response mediator protein 5 and amphiphysin 102. Antineuronal nuclear antibodies 1 and 2, prostate cancer antigen-1 and glutamate decarboxylase-65 also occur in paraneoplastic myelopathy 105. The most common associated cancers are lung and breast, but others include kidney, thyroid, ovarian, lymphoma and melanoma 102 105.…”

Mycophenolate mofetil in paediatric autoimmune or immune‐mediated diseases of the central nervous system: clinical experience and recommendations

“…MMF regimes for children are often extrapolated from adult data and recommend a dose of approximately 40mg/kg/d, sometimes up to 50mg/kg/d (although dose per square metre is generally more accurate in the paediatric age group: 600mg/m 2 /dose twice a day) (median dose in our cohort: 35mg/kg/d). Regarding suboptimal treatment duration, it should be noted that the initiation of a chronic treatment such as MMF or azathioprine may have a slow onset of efficacy, and there should initially be overlap with another immune therapy for a certain time, up to 6 to 8 months . Relapses on MMF were also associated with a high rate of medication weaning or recent discontinuation of an immune therapy other than MMF no more than 2 months before the event (31 out of 34), possibly supporting the hypothesis of a premature steroid discontinuation or steroid dependence.…”

Review of the Etiological Causes and Diagnosis of Myelitis and Its Medical Orientation Protocol

“…In addition, Positron-emission tomography (PET) scan may increase the diagnostic yield for certain cancers where other modalities have been negative/uninformative. PET imaging alone, or in combination with anatomic data (PET-CT), increases the cancer diagnostic yield by 20% [31].…”