Characteristics of 212 patients with GAD65 neurological autoimmunity*
| All GAD65 neurological autoimmunity (n=212) | Stiff-person spectrum disorders (SPSD) (n=71) | Cerebellar ataxia (n=55) | Epilepsy (n=35) | Limbic encephalitis (LE)† (n=7) | Overlap Syndromes‡ (n=44) | P value | |
| Median age at symptom onset in years (range) | 46 (5–83) | 46 (5–76) | 59 (14–83) | 24 (5–56) | 45 (23–65) | 46 (10–70) | <0.0001 |
| Female (%) | 163/212 (77) | 53/71 (75) | 42/55 (76) | 30/35 (86) | 6/7 (86) | 32/44 (73) | 0.65 |
| Caucasian (%) | 157/196 (80) | 52/68 (76) | 44/50 (88) | 26/33 (79) | 6/6 (100) | 29/39 (74) | 0.21 |
| Median total symptom duration recorded in months (range) | 76 (3–636) | 90 (6–624) | 42 (3–171) | 137 (3–552) | 72 (18–221) | 89.5 (6–636) | <0.0001 |
| Systemic autoimmunity (%) | 125/212 (59) | 43/71 (61) | 36/55 (65) | 19/35 (54) | 4/7 (57) | 23/44 (52) | 0.70 |
| T1DM (%) | 63/212 (30) | 23/71 (32) | 18/55 (33) | 9/35 (26) | 0/7 (0) | 13/44 (30) | – |
| Thyroid disease (%) | 72/212 (34) | 27/71 (38) | 20/55 (36) | 11/35 (31) | 2/7 (29) | 12/44 (27) | – |
| Pernicious anaemia (%) | 40/212 (19) | 14/71 (20) | 11/55 (20) | 3/35 (9) | 2/7 (29) | 10/44 (23) | – |
| Other (%)§ | 21/212 (10) | 6/71 (8) | 7/55 (13) | 5/35 (14) | 0/7 | 3/44 (7) | – |
| Cancer diagnosed within 5 years of symptom onset (%)¶ | 9/212 (4) | 0/71 (0) | 6/55 (11) | 1/35 (3) | 1/7 (14) | 1/44 (2) | 0.01 |
| Median serum anti-GAD65 titre in nmol/L (range) | 534 (20.1–7558) | 537 (25.6–7558) | 464 (21.5–4040) | 423 (33.1–4415) | 415 (34–1481) | 667.5 (20.1–6960) | 0.43 |
| Median CSF anti-GAD65 titre in nmol/L (range)** | 10 (0.1–274) | 6.5 (0.2–163) | 17.6 (1.2–274) | 2.5 (0.3–52.3) | 14.2 (0.2–102) | 14 (0.1–214) | 0.10 |
| CSF pleocytosis (%) | 15/127 (12) | 4/33 (12) | 4/36 (11) | 2/24 (8) | 2/6 (33) | 3/28 (11) | 0.56 |
| CSF-specific OCB (%) | 46/114 (40) | 10/30 (33) | 13/31 (42) | 8/21 (38) | 3/5 (60) | 12/27 (44) | 0.79 |
| Elevated CSF protein (%) | 78/122 (64) | 20/34 (59) | 20/33 (61) | 15/24 (63) | 4/6 (67) | 19/25 (76) | 0.71 |
| Elevated CSF IgG index (%) | 10/108 (9) | 2/31 (6) | 5/27 (19) | 0/22 (0) | 1/4 (25) | 2/24 (8) | 0.17 |
*Regarding other neural antibodies identified that were potentially relevant to disease manifestation, 3 patients had glycine receptor α1 subunit-specific antibodies (two SPSD, 1 overlap of SPSD, cerebellar ataxia and epilepsy), 1 patient with epilepsy had collapsin response-mediator protein 5 antibodies (diagnosed with thymoma, not classified as LE due to absence of medial temporal lobe T2-hyperintensity on brain MRI), and one patient with epilepsy had a clinicoradiographic presentation that was in retrospect concerning for gamma-aminobutyric acid type A antibodies but confirmatory testing was not performed (described in text).
†All patients with LE had epilepsy; as such, LE with epilepsy alone was not classified as an overlap syndrome.
‡Of patients with overlap syndromes, SPSD was reported in 36/44, cerebellar ataxia in 36/44, epilepsy without LE in 17/44, and LE in 3/44.
§Other systemic autoimmunity includes adrenal insufficiency, vitiligo and coeliac disease.
¶Cancers diagnosed included thyroid cancer (4: 2 papillary thyroid cancer, 2 not otherwise specified), breast cancer (3: 1 ductal carcinoma, 2 not otherwise specified), lung cancer (3: 1 large cell neuroendocrine carcinoma, 1 small cell lung cancer, 1 bronchioalveolar carcinoma), and thymoma (1). Two patients had both breast and thyroid cancer diagnosed. Seven of 9 patients had a cancer diagnosed within 2 years of symptom onset, while the remaining two patients had cancer diagnosed 2–5 years from symptom onset (one thyroid cancer not otherwise specified, 1 breast cancer not otherwise specified).
**Testing for anti-GAD65 in CSF was performed in 93/212 patients.
CSF, cerebrospinal fluid; GAD65, glutamic acid decarboxylase-65; OCB, oligoclonal bands; T1DM, type 1 diabetes mellitus.