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


CONCLUSIONS
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.
From the Departments of Neurology (B.B., S.J., S.N., H.-M.M.) and Nuclear Medicine (U.H.), University of Heidelberg; Institute for Experimental Immunology (C.P., I.M.B., R.B., L.K., W.S.), Euroimmun, Lübeck; Department of Neurology (A.K.), Klinikum Bremen Ost; and Department of Neurology (M.K.), Community Hospital Herdecke, Germany.
Bettina
B
Balint
Sven
S
Jarius
Simon
S
Nagel
Uwe
U
Haberkorn
Christian
C
Probst
Inga Madeleine
IM
Blöcker
Ramona
R
Bahtz
Lars
L
Komorowski
Winfried
W
Stöcker
Andreas
A
Kastrup
Martin
M
Kuthe
Hans-Michael
HM
Meinck
D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood* / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000276:immunology*; D004576:Electromyography; D004679:Encephalomyelitis / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D008297:Male; D009127:Muscle Rigidity / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D009207:Myoclonus / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology*; D015221:Potassium Channels / Q000276:immunology*; D055815:Young Adult
D000906:Antibodies; D016756:Immunoglobulins, Intravenous; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; C503535:DPP6 protein, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases