Progressive encephalomyelitis with rigidity and myoclonus: a new variant with DPPX antibodies

Neurology. 2014 Apr 29;82(17):1521-8. doi: 10.1212/WNL.0000000000000372. Epub 2014 Apr 2.


Objective: To describe a novel and distinct variant of progressive encephalomyelitis with rigidity and myoclonus (PERM) associated with antibodies directed against dipeptidyl peptidase-like protein 6 (DPPX), a regulatory subunit of the Kv4.2 potassium channels on the surface of neurons.

Methods: Case series describing the clinical, paraclinical, and serologic features of 3 patients with PERM. A recombinant, cell-based indirect immunofluorescence assay with DPPX-expressing HEK293 cells was used to detect DPPX antibodies in conjunction with mammalian tissues.

Results: All patients presented with a distinct syndrome involving hyperekplexia, prominent cerebellar ataxia with marked eye movement disorder, and trunk stiffness of variable intensity. Additional symptoms comprised allodynia, neurogenic pruritus, and gastrointestinal symptoms. Symptoms began insidiously and progressed slowly. An inflammatory CSF profile with mild pleocytosis and intrathecal immunoglobulin G synthesis was found in all patients. High DPPX antibody titers were detected in the patients' serum and CSF, with specific antibody indices suggestive of intrathecal synthesis of DPPX antibodies. Response to immunotherapy was good, but constant and aggressive treatment may be required.

Conclusion: These cases highlight the expanding spectrum of both PERM and anti-neuronal antibodies. Testing for DPPX antibodies should be considered in the diagnostic workup of patients with acquired hyperekplexia, cerebellar ataxia, and stiffness, because such patients might benefit from immunotherapy. Further studies are needed to elucidate both the entire clinical spectrum associated with DPPX antibodies and their role in pathogenesis.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Antibodies / blood*
  • Antibodies / cerebrospinal fluid
  • Brain / metabolism
  • Brain / pathology
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / immunology*
  • Electromyography
  • Encephalomyelitis / blood*
  • Encephalomyelitis / complications
  • Encephalomyelitis / drug therapy
  • Encephalomyelitis / immunology
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Male
  • Muscle Rigidity / blood*
  • Muscle Rigidity / complications
  • Muscle Rigidity / drug therapy
  • Muscle Rigidity / immunology
  • Myoclonus / blood*
  • Myoclonus / complications
  • Myoclonus / drug therapy
  • Myoclonus / immunology
  • Nerve Tissue Proteins / immunology*
  • Potassium Channels / immunology*
  • Young Adult


  • Antibodies
  • Immunoglobulins, Intravenous
  • Nerve Tissue Proteins
  • Potassium Channels
  • DPP6 protein, human
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases

Supplementary concepts

  • Progressive Encephalomyelitis with Rigidity