Cerebellar ataxia and glutamic acid decarboxylase antibodies: immunologic profile and long-term effect of immunotherapy.

Helena Ariño, Nuria Gresa-Arribas, Yolanda Blanco, Eugenia Martínez-Hernández, Lidia Sabater, Mar Petit-Pedrol, Idoia Rouco, Luis Bataller, Josep O. Dalmau, Albert Saiz, Francesc Graus
JAMA Neurol. 2014-08-01; 71(8): 1009
DOI: 10.1001/jamaneurol.2014.1011

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Ariño H(1), Gresa-Arribas N(2), Blanco Y(1), Martínez-Hernández E(1), Sabater L(2), Petit-Pedrol M(2), Rouco I(3), Bataller L(4), Dalmau JO(5), Saiz A(1), Graus F(1).

Author information:
(1)Neurology Service, Hospital Clínic, Barcelona, Spain2Neuroimmunology Program, Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of
Barcelona, Barcelona, Spain.
(2)Neuroimmunology Program, Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
(3)Neurology Service, Department of Neurosciences, Cruces University Hospital, University of the Basque Country, Bizkaia, Spain.
(4)Neurology Service, University Hospital Politècnic La Fe, Valencia, Spain.
(5)Neuroimmunology Program, Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain5Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain6Department of Neurology, University of Pennsylvania, Philadelp.

IMPORTANCE: Current clinical and immunologic knowledge on cerebellar ataxia (CA)
with glutamic acid decarboxylase 65 antibodies (GAD65-Abs) is based on case
reports and small series with short-term follow-up data.
OBJECTIVE: To report the symptoms, additional antibodies, prognostic factors, and
long-term outcomes in a cohort of patients with CA and GAD65-Abs.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study and laboratory
investigations at a center for autoimmune neurologic disorders among 34 patients
with CA and GAD65-Abs, including 25 with long-term follow-up data (median, 5.4
years; interquartile range, 3.1-10.3 years).
MAIN OUTCOMES AND MEASURES: Analysis of clinicoimmunologic features and
predictors of response to immunotherapy. Immunochemistry on rat brain, cultured
neurons, and human embryonic kidney cells expressing GAD65, GAD67, α1-subunit of
the glycine receptor, and a repertoire of known cell surface autoantigens were
used to identify additional antibodies. Twenty-eight patients with stiff person
syndrome and GAD65-Abs served as controls.
RESULTS: The median age of patients was 58 years (range, 33-80 years); 28 of 34
patients (82%) were women. Nine patients (26%) reported episodes of brainstem and
cerebellar dysfunction or persistent vertigo several months before developing CA.
The clinical presentation was subacute during a period of weeks in 13 patients
(38%). Nine patients (26%) had coexisting stiff person syndrome symptoms.
Systemic organ-specific autoimmunities (type 1 diabetes mellitus and others) were
present in 29 patients (85%). Twenty of 25 patients with long-term follow-up data
received immunotherapy (intravenous immunoglobulin in 10 and corticosteroids and
intravenous immunoglobulin or other immunosuppressors in 10), and 7 of them (35%)
improved. Predictors of clinical response included subacute onset of CA (odds
ratio [OR], 0.50; 95% CI, 0.25-0.99; P = .047) and prompt immunotherapy (OR,
0.98; 95% CI, 0.96-0.99; P = .01). Similar frequencies of serum GAD67-Abs were
found in patients with CA (24 of 34 patients [71%]) and in patients with stiff
person syndrome (20 of 28 patients [71%]). However, GAD67-Abs were found in all
of the cerebrospinal fluid samples examined (22 samples from patients with CA and
17 samples from patients with stiff person syndrome). Glycine receptor antibodies
but not other cell surface antibodies were identified in 4 patients with CA. The
presence of glycine receptor antibodies did not correlate with any specific
clinical feature.
CONCLUSIONS AND RELEVANCE: In patients with CA and GAD65-Abs, subacute onset of
symptoms and prompt immunotherapy are associated with good outcome. Persistent
vertigo or brainstem and cerebellar episodes can herald CA and should lead to
GAD65-Ab testing, particularly in patients with systemic organ-specific


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