Abstract
Stiff Person Syndrome (SPS) is a rare autoimmune disorder associated with antibodies against glutamic acid decarboxylase (GAD-Ab), the key enzyme in γ-aminobutyric acid synthesis (GABA). In order to investigate the role of cerebral benzodiazepinereceptor binding in SPS, we performed [11C]flumazenil (FMZ) positron emission tomography (PET) in a female patient with SPS compared to nine healthy controls. FMZ is a radioligand to the postsynaptic central benzodiazepine receptor which is co-localized with the GABA-A receptor. In the SPS patient, we found a global reduction of cortical FMZ binding. In addition, distinct local clusters of reduced radiotracer binding were observed. These data provide first in vivo evidence for a reduced postsynaptic GABA-A receptor availability which may reflect the loss of GABAergic neuronal inhibition in SPS.
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References
Dalakas MC, Fujii M, Li M, McElroy B (2000) The clinical spectrum of anti- GAD antibody-positive patients with stiff-person syndrome. Neurology 55:1531–1535
Eden RJ, Costall B, Domeney AM, Gerrard PA, Harvey CA, Kelly ME, Naylor RJ, Owen DA, Wright A (1991) Preclinical pharmacology of ropinirole (SK&F 101468-A) a novel dopamine D2 agonist. Pharmacol Biochem Behav 38:147–154
Faingold CL (2002) Role of GABA abnormalities in the inferior colliculus pathophysiology – audiogenic seizures. Hear Res 168:223–237
Heiss WD, Graf R, Fujita T, Ohta K, Bauer B, Lottgen J, Wienhard K (1997) Early detection of irreversibly damaged ischemic tissue by flumazenil positron emission tomography in cats. Stroke 28:2045–2051; discussion 2051–2042
Heiss WD, Kracht LW, Thiel A, Grond M, Pawlik G (2001) Penumbral probability thresholds of cortical flumazenil binding and blood flow predicting tissue outcome in patients with cerebral ischaemia. Brain 124:20–29
Levy LM, Hallett M (2002) Impaired brain GABA in focal dystonia. Ann Neurol 51:93–101
Levy LM, Levy-Reis I, Fujii M, Dalakas MC (2005) Brain gamma-aminobutyric acid changes in stiff-person syndrome. Arch Neurol 62:970–974
Lingamaneni R, Hemmings HC Jr (2003) Differential interaction of anaesthetics and antiepileptic drugs with neuronal Na+ channels, Ca2+ channels, and GABA(A) receptors. Br J Anaesth 90:199–211
Meinck HM (2000) Stiff-man syndrome from neurological perspective. Internist (Berl) 41:455–459
Meinck HM, Faber L, Morgenthaler N, Seissler J, Maile S, Butler M, Solimena M, DeCamilli P, Scherbaum WA (2001) Antibodies against glutamic acid decarboxylase: prevalence in neurological diseases. J Neurol Neurosurg Psychiatry 71:100–103
Meinck HM, Thompson PD (2002) Stiff man syndrome and related conditions. Mov Disord 17:853–866
Meyer M, Koeppe RA, Frey KA, Foster NL, Kuhl DE (1995) Positron emission tomography measures of benzodiazepine binding in Alzheimer’s disease. Arch Neurol 52:314–317
Perani D, Garibotto V, Moresco RM, Ortelli P, Corbo M, Fazio F, Folli F (2007) PET evidence of central GABAergic changes in stiff-person syndrome. Mov Disord 22:1030–1033
Raju R, Rakocevic G, Chen Z, Hoehn G, Semino-Mora C, Shi W, Olsen R, Dalakas M (2006) Autoimmunity to GABAA-receptor-associated protein in stiff-person syndrome. Brain 129:3270–3276
Rudolf J, Sobesky J, Ghaemi M, Heiss WD (2002) The correlation between cerebral glucose metabolism and benzodiazepine receptor density in the acute vegetative state. Eur J Neurol 9:671–677
Rudolf J, Sobesky J, Grond M, Heiss WD (2000) Identification by positron emission tomography of neuronal loss in acute vegetative state. Lancet 355:115–116
Sandrini M, Vergoni AV, Bertolini A (1993) No modifications of GABAA and benzodiazepine receptors following experimental dysthyroidism in rats. Pharmacol Res 28:47–52
Szelies B, Sobesky J, Pawlik G, Mielke R, Bauer B, Herholz K, Heiss WD (2002) Impaired benzodiazepine receptor binding in peri-lesional cortex of patients with symptomatic epilepsies studied by [(11)C]-flumazenil PET. Eur J Neurol 9:137–142
Talairach J, Tournoux P (1988) Coplanar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System – an Approach to Cerebral Imaging. Thieme, New York
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Open Access This is an open access article distributed under the terms of the Creative Commons Attribution Noncommercial License ( https://creativecommons.org/licenses/by-nc/2.0 ), which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
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Galldiks, N., Thiel, A., Haense, C. et al. 11C-Flumazenil positron emission tomography demonstrates reduction of both global and local cerebral benzodiazepine receptor binding in a patient with Stiff Person Syndrome. J Neurol 255, 1361–1364 (2008). https://doi.org/10.1007/s00415-008-0920-9
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DOI: https://doi.org/10.1007/s00415-008-0920-9