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2014 ; 71
(8
): 1009-16
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Cerebellar ataxia and glutamic acid decarboxylase antibodies: immunologic profile
and long-term effect of immunotherapy
#MMPMID24934144
Ariño H
; Gresa-Arribas N
; Blanco Y
; Martínez-Hernández E
; Sabater L
; Petit-Pedrol M
; Rouco I
; Bataller L
; Dalmau JO
; Saiz A
; Graus F
JAMA Neurol
2014[Aug]; 71
(8
): 1009-16
PMID24934144
show ga
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, ?1-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 autoimmunities.
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