Antibody-associated CNS syndromes without signs of inflammation in the elderly

Neurology. 2017 Oct 3;89(14):1471-1475. doi: 10.1212/WNL.0000000000004541. Epub 2017 Sep 6.

Abstract

Objective: To report the CNS syndromes of patients ≥60 years of age with antibodies against neuronal surface antigens but no evidence of brain MRI and CSF inflammatory changes.

Methods: This was a retrospective clinical analysis of patients with antibodies against neuronal surface antigens who fulfilled 3 criteria: age ≥60 years, no inflammatory abnormalities in brain MRI, and no CSF pleocytosis. Antibodies were determined with reported techniques.

Results: Among 155 patients ≥60 years of age with neurologic syndromes related to antibodies against neuronal surface antigens, 35 (22.6%) fulfilled the indicated criteria. The median age of these 35 patients was 68 years (range 60-88 years). Clinical manifestations included faciobrachial dystonic seizures (FBDS) in 11 of 35 (31.4%) patients, all with LGI1 antibodies; a combination of gait instability, brainstem dysfunction, and sleep disorder associated with IgLON5 antibodies in 10 (28.6%); acute confusion, memory loss, and behavioral changes suggesting autoimmune encephalitis (AE) in 9 (25.7%; 2 patients with AMPAR, 2 with NMDAR, 2 with GABAbR, 2 with LGI1, and 1 with CASPR2 antibodies); and rapidly progressive cognitive deterioration in 5 (14.3%; 3 patients with IgLON5 antibodies, 1 with chorea; 1 with DPPX antibody-associated cerebellar ataxia and arm rigidity; and 1 with CASPR2 antibodies).

Conclusions: In patients ≥60 years of age, the correct identification of characteristic CNS syndromes (FBDS, anti-IgLON5 syndrome, AE) should prompt antibody testing even without evidence of inflammation in MRI and CSF studies. Up to 15% of the patients developed rapidly progressive cognitive deterioration, which further complicated the differential diagnosis with a neurodegenerative disorder.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging
  • Antibodies / metabolism*
  • Cell Adhesion Molecules, Neuronal / immunology
  • Central Nervous System / immunology*
  • Central Nervous System / metabolism*
  • Female
  • HEK293 Cells
  • Humans
  • Inflammation
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Nervous System Diseases / immunology*
  • Nervous System Diseases / pathology*
  • Proteins / immunology
  • Receptors, GABA-B / immunology
  • Retrospective Studies

Substances

  • Antibodies
  • Cell Adhesion Molecules, Neuronal
  • IgLON5 protein, human
  • Intracellular Signaling Peptides and Proteins
  • LGI1 protein, human
  • Proteins
  • Receptors, GABA-B