Abstract
A number of cortical and spinal excitability variables have been tested in a patient with Stiff Person Syndrome (SPS), before and after immunotherapy with mycophenolate mofetil, intravenous immunoglobulin and corticosteroids, which normalized plasma levels of anti-GAD antibodies and dramatically improved the clinical picture. The overlapping time-course of neurophysiological, clinical and bio-umoral findings suggests that immunotherapy might have changed GABA/Glutamate balance at cortical level, favoring the former, as reflected by normalization of the startle reflex, lengthening of the cortical silent period and clear-cut reduction of intracortical facilitation to paired-pulse transcranial magnetic stimulation. This represents the first report investigating effects of immunotherapy on cortical excitability in SPS.
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References
Dalakas MC, Fuji M, Li M, McRoy B (2000) The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome. Neurology 55:1531–1535
Meinck HM, Ricker K, Conrad B (1984) The stiff-man syndrome: new pathophysiological aspects from abnormal exteroceptive reflexes and the response to clomipramine, clonidine, and tizanidine. J Neurol Neurosurg Psychiatry 47:280–287
Perani D, Garibotto V, Moresco RM et al (2007) PET evidence of central GABAergic changes in stiff-person syndrome. Mov Dis 22:1030–1033
Levy LM, Levy-Reis I, Fujii M, Dalakas MC (2005) Brain aminobutyric acid changes in stiff-person syndrome. Arch Neurol 62:970–974
Rossini PM, Rossi S (2007) Transcranial magnetic stimulation. Diagnostic, therapeutic and research potential. Neurology 68:484–488
Chen R, Cros D, Curra A et al (2008) The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 119:504–532
Koerner C, Wieland B, Richter W, Meinck HM (2004) Stiff-person syndromes. Motor cortex hyperexcitability correlates with anti-GAD autoimmunity. Neurology 62:1357–1362
Ziemann U, Rothwell JC, Ridding MC (1996) Interaction between intracortical inhibition and facilitation in human motor cortex. J Physiol (Lond) 496:873–881
Di Lazzaro V, Oliviero A, Meglio M et al (2000) Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex. Clin Neurophysiol 111:794–799
Yu M (2007) Recent developments of the PET imaging agents for metabotropic glutamate receptor subtype 5. Curr Top Med Chem 7:1800–1805
Dalakas MCJ (2005) The role of IVIg in the treatment of patients with stiff person syndrome and other neurological diseases associated with anti-GAD antibodies. J Neurol 252(Suppl 1):119–125
Rossini PM, Barker AT, Berardelli A et al (1994) Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalogr Clin Neurophysiol 91:79–92
Ziemann U, Lo¨nnecker S, Steinhoff BJ, Paulus W (1996) Effects of antiepileptic drugs on motor cortex excitability in humans: a transcranial magnetic stimulation study. Ann Neurol 40:367–378
Tokimura H, Di Lazzaro V, Tokimura Y et al (2000) Short latency inhibition of human hand motor cortex by somatosensory input from the hand. J Physiol (Lond) 523:503–513
Di Lazzaro V, Oliviero A, Saturno E et al (2005) Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans. J Physiol 564:661–668
Di Lazzaro V, Pilato F, Di leone M, Proficue P, Ranieri F, Ricci V et al (2007) Segregating two inhibitory circuits in human motor cortex at the level of GABAA receptor subtypes: a TMS study. Clin Neurophysiol 118:2207–2214
Ziemann U, Lonnecker S, Steinhoff BJ, Paulus W (1996) The effect of lorazepam on the motor cortical excitability in man. Exp Brain Res 109:127–135
Siebner HR, Dressnandt J, Auer C, Conrad B (1998) Continuous intrathecal baclofen infusions induced a marked increase of the transcranially evoked silent period in a patient with generalized dystonia. Muscle Nerve 21:1209–1212
Hanajima R, Ugawa Y, Terao Y et al (1998) Paired-pulse magnetic stimulation of the human motor cortex: differences among I waves. J Physiol (Lond) 509:607–618
Ziemann U, Chen R, Cohen LG, Hallett M (1998) Dextromethorphan decreases the excitability of the human motor cortex. Neurology 51:1320–1324
Rossi S, De Capua A, Tavanti M, Calossi S, Polizzotto NR, Mantovani A, Falzarano V, Bossini L, Passero S, Bartalini S, Ulivelli M (2009) Dysfunctions of cortical excitability in drug-naive posttraumatic stress disorders patients. Biol Psychiatry 66:54–61
Sandbrink F, Ali Syed N, Fuji MD, Akas C, Floeter MK (2000) Motor cortex excitability in stiff-person syndrome. Brain 123:2231–2239
Matsumoto JY, Caviness JN, McEvoy KM (1994) The acoustic startle reflex in stiff-man syndrome. Neurology 44:1952–1955
Meinck HM, Ricker K, Hulser PJ, Solimena M (1995) Stiff man syndrome: neurophysiological findings in eight patients. J Neurol 242:134–142
Floeter MK, Valls Solè JP, Toro C, Hallett M (1998) Physiologic studies of spinal inhibitory circuits in patients with stiff-person syndrome. Neurology 51:85–93
Lorish TR, Thorsteinsson G, Howard FM Jr (1989) Stiff-man syndrome updated [Review]. Mayo Clin Proc 64:624–636
Baker MR, Das M, Isaacs J, Fawcett PRW, Bates D (2005) Treatment of stiff person syndrome with rituximab. J Neurol Neurosurg Psychiatry 76:999–1001
Lockman J, Burns TM (2007) Stiff-person syndrome. Curr Treat Options Neurol 9:234–240
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Rossi, S., Ulivelli, M., Malentacchi, M. et al. Effects of immunotherapy on motor cortex excitability in Stiff Person Syndrome. J Neurol 257, 281–285 (2010). https://doi.org/10.1007/s00415-009-5331-z
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DOI: https://doi.org/10.1007/s00415-009-5331-z