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

Abstract

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.

• Authors: Bettina Balint, Sven Jarius, Simon Nagel, Uwe Haberkorn, Christian Probst, Inga Madeleine Blöcker, Ramona Bahtz, Lars Komorowski, Winfried Stöcker, Andreas Kastrup, Martin Kuthe, Hans-Michael Meinck
• Journal: Neurology (Neurology) Vol. 82 Issue 17 Pg. 1521-8 (Apr 29 2014) ISSN: 1526-632X [Electronic] United States
• PMID: 24696508 (Publication Type: Case Reports, Journal Article)

Chemical References

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

Topics

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