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2017 ; 4
(ä): 16
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Immune-mediated cerebellar ataxias: from bench to bedside
#MMPMID28944066
Mitoma H
; Manto M
; Hampe CS
Cerebellum Ataxias
2017[]; 4
(ä): 16
PMID28944066
show ga
The cerebellum is a vulnerable target of autoimmunity in the CNS. The category of
immune-mediated cerebellar ataxias (IMCAs) was recently established, and includes
in particular paraneoplastic cerebellar degenerations (PCDs), gluten ataxia (GA)
and anti-GAD65 antibody (Ab) associated-CA, all characterized by the presence of
autoantibodies. The significance of onconeuronal autoantibodies remains uncertain
in some cases. The pathogenic role of anti-GAD65Ab has been established both in
vitro and in vivo, but a consensus has not been reached yet. Recent studies of
anti-GAD65 Ab-associated CA have clarified that (1) autoantibodies are generally
polyclonal and elicit pathogenic effects related to epitope specificity, and (2)
the clinical course can be divided into two phases: a phase of functional
disorder followed by cell death. These features provide the rationale for prompt
diagnosis and therapeutic strategies. The concept "Time is brain" has been
completely underestimated in the field of immune ataxias. We now put forward the
concept "Time is cerebellum" to underline the importance of very early
therapeutic strategies in order to prevent or stop the loss of neurons and
synapses. The diagnosis of IMCAs should depend not only on Ab testing, but rather
on a rapid and comprehensive assessment of the clinical/immune profile. Treatment
should be applied during the period of preserved cerebellar reserve, and should
encompass early removal of the conditions (such as remote primary tumors) or
diseases that trigger the autoimmunity, followed by the combinations of various
immunotherapies.