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Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association.
Brain 2008; 131(Pt 10):2553-63B

Abstract

The association of high levels of autoantibodies to glutamic acid decarboxylase (GAD-ab) and stiff-person syndrome (SPS) is well known. However, the full spectrum of neurological syndromes associated with GAD-ab is not well established. In addition, these patients usually present type 1 diabetes mellitus (DM1) that could justify the presence of high GAD-ab levels. To clarify these issues, we reviewed the clinical and immunological features of patients in whom high GAD-ab levels were detected in a reference centre for DM1 and for the detection of antineuronal antibodies in suspected paraneoplastic neurological syndromes (PNS). High GAD-ab levels were defined as values > or =2000 U/ml by radioimmunoassay. Intrathecal synthesis (IS) of GAD-ab was calculated in paired serum/CSF samples. Values higher than the IgG index were considered indicators for positive GAD-ab-specific IS. High GAD-ab levels were identified in 61 patients, 22 (36%) had SPS, 17 (28%) cerebellar ataxia, 11 (18%) other neurological disorders (epilepsy -- four, PNS -- four; idiopathic limbic encephalitis -- two; myasthenia gravis -- one), and 11 (18%) isolated DM1. Patients with SPS and cerebellar ataxia had the same frequency of female gender (86% vs 94%), DM1 (59% vs 53%), CSF oligoclonal bands (35% vs 69%). Three of the four PNS patients, with paraneoplastic encephalomyelitis, a predominant gait cerebellar ataxia, and limbic encephalitis, had neuroendocrine carcinomas. GAD expression was confirmed in the two tumours in which the study was done. The fourth patient presented with paraneoplastic cerebellar degeneration antedating a lung adenocarcinoma. The frequency of increased IS of GAD-ab was 85% in SPS, 100% in cerebellar ataxia, and 86% in other neurological disorders. In conclusion, our study emphasizes that high GAD-ab levels associate with other neurological disorders besides SPS. Cerebellar ataxia, the second most common syndrome associated with high GAD-ab levels, shares with SPS the same demographic, clinical and immunological features. The demonstration of an increased IS of GAD-ab is important to confirm that the GAD autoimmunity is related to the neurological syndrome particularly when there is a concomitant DM1 that could justify the presence of high GAD-ab levels. Lastly, in patients who develop neurological syndromes that suggest a PNS, the finding of GAD-ab does not rule out this possibility and appropriate studies should be done to confirm an underlying cancer.

Authors+Show Affiliations

Service of Neurology, Hospital Clinic and Institut d' Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18687732

Citation

Saiz, Albert, et al. "Spectrum of Neurological Syndromes Associated With Glutamic Acid Decarboxylase Antibodies: Diagnostic Clues for This Association." Brain : a Journal of Neurology, vol. 131, no. Pt 10, 2008, pp. 2553-63.
Saiz A, Blanco Y, Sabater L, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain. 2008;131(Pt 10):2553-63.
Saiz, A., Blanco, Y., Sabater, L., González, F., Bataller, L., Casamitjana, R., ... Graus, F. (2008). Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain : a Journal of Neurology, 131(Pt 10), pp. 2553-63. doi:10.1093/brain/awn183.
Saiz A, et al. Spectrum of Neurological Syndromes Associated With Glutamic Acid Decarboxylase Antibodies: Diagnostic Clues for This Association. Brain. 2008;131(Pt 10):2553-63. PubMed PMID: 18687732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. AU - Saiz,Albert, AU - Blanco,Yolanda, AU - Sabater,Lidia, AU - González,Félix, AU - Bataller,Luis, AU - Casamitjana,Roser, AU - Ramió-Torrentà,Lluis, AU - Graus,Francesc, Y1 - 2008/08/07/ PY - 2008/8/9/pubmed PY - 2008/12/23/medline PY - 2008/8/9/entrez SP - 2553 EP - 63 JF - Brain : a journal of neurology JO - Brain VL - 131 IS - Pt 10 N2 - The association of high levels of autoantibodies to glutamic acid decarboxylase (GAD-ab) and stiff-person syndrome (SPS) is well known. However, the full spectrum of neurological syndromes associated with GAD-ab is not well established. In addition, these patients usually present type 1 diabetes mellitus (DM1) that could justify the presence of high GAD-ab levels. To clarify these issues, we reviewed the clinical and immunological features of patients in whom high GAD-ab levels were detected in a reference centre for DM1 and for the detection of antineuronal antibodies in suspected paraneoplastic neurological syndromes (PNS). High GAD-ab levels were defined as values > or =2000 U/ml by radioimmunoassay. Intrathecal synthesis (IS) of GAD-ab was calculated in paired serum/CSF samples. Values higher than the IgG index were considered indicators for positive GAD-ab-specific IS. High GAD-ab levels were identified in 61 patients, 22 (36%) had SPS, 17 (28%) cerebellar ataxia, 11 (18%) other neurological disorders (epilepsy -- four, PNS -- four; idiopathic limbic encephalitis -- two; myasthenia gravis -- one), and 11 (18%) isolated DM1. Patients with SPS and cerebellar ataxia had the same frequency of female gender (86% vs 94%), DM1 (59% vs 53%), CSF oligoclonal bands (35% vs 69%). Three of the four PNS patients, with paraneoplastic encephalomyelitis, a predominant gait cerebellar ataxia, and limbic encephalitis, had neuroendocrine carcinomas. GAD expression was confirmed in the two tumours in which the study was done. The fourth patient presented with paraneoplastic cerebellar degeneration antedating a lung adenocarcinoma. The frequency of increased IS of GAD-ab was 85% in SPS, 100% in cerebellar ataxia, and 86% in other neurological disorders. In conclusion, our study emphasizes that high GAD-ab levels associate with other neurological disorders besides SPS. Cerebellar ataxia, the second most common syndrome associated with high GAD-ab levels, shares with SPS the same demographic, clinical and immunological features. The demonstration of an increased IS of GAD-ab is important to confirm that the GAD autoimmunity is related to the neurological syndrome particularly when there is a concomitant DM1 that could justify the presence of high GAD-ab levels. Lastly, in patients who develop neurological syndromes that suggest a PNS, the finding of GAD-ab does not rule out this possibility and appropriate studies should be done to confirm an underlying cancer. SN - 1460-2156 UR - https://www.unboundmedicine.com/medline/citation/18687732/Spectrum_of_neurological_syndromes_associated_with_glutamic_acid_decarboxylase_antibodies:_diagnostic_clues_for_this_association_ L2 - https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awn183 DB - PRIME DP - Unbound Medicine ER -