Skip to main content
Top
Published in: Journal of Neurology 3/2010

01-03-2010 | Original Communication

SPECT and PET analysis of subthalamic stimulation in Parkinson’s disease: analysis using a manual segmentation

Authors: Claire Haegelen, Daniel García-Lorenzo, Florence Le Jeune, Julie Péron, Bernard Gibaud, Laurent Riffaud, Gilles Brassier, Christian Barillot, Marc Vérin, Xavier Morandi

Published in: Journal of Neurology | Issue 3/2010

Login to get access

Abstract

The subthalamic nucleus (STN) has become an effective target of deep-brain stimulation (DBS) in severely disabled patients with advanced Parkinson’s disease (PD). Clinical studies have reported DBS-induced adverse effects on cognitive functions, mood, emotion and behavior. STN DBS seems to interfere with the limbic functions of the basal ganglia, but the limbic effects of STN DBS are controversial. We measured prospectively resting regional cerebral metabolism (rCMb) with 18-fluorodeoxyglucose and PET, and resting regional cerebral blood flow (rCBF) with HMPAO and SPECT in six patients with Parkinson’s disease. We compared PET and SPECT 1 month before and 3 months after STN DBS. On cerebral MRI, 13 regions of interest (ROI) were manually delineated slice by slice in frontal and limbic lobes. We obtained mean rCBF and rCMb values for each ROI and the whole brain. We normalized rCBF and rCMB values to ones for the whole brain volume, which we compared before and following STN DBS. No significant difference emerged in the SPECT analysis. PET analysis revealed a significant decrease in rCMb following STN DBS in the superior frontal gyri and left and right dorsolateral prefrontal cortex (p < 0.05). A non-significant decrease in rCMb in the left anterior cingulate gyrus appeared following STN DBS (p = 0.075). Our prospective SPECT and PET study revealed significantly decreased glucose metabolism of the two superior frontal gyri without any attendant perfusion changes following STN DBS. These results suggest that STN DBS may change medial prefrontal function and therefore the integration of limbic information, either by disrupting emotional processes within the STN, or by hampering the normal function of a limbic circuit.
Literature
1.
go back to reference Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 9:357–381CrossRefPubMed Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 9:357–381CrossRefPubMed
2.
go back to reference Benabid AL, Krack P, Benazzouz A, Limousin P, Koudsie A, Pollak P (2000) Deep brain stimulation of the subthalamic nucleus for Parkinson’s disease: methodologic aspects and clinical criteria. Neurology 55:S40–S44PubMed Benabid AL, Krack P, Benazzouz A, Limousin P, Koudsie A, Pollak P (2000) Deep brain stimulation of the subthalamic nucleus for Parkinson’s disease: methodologic aspects and clinical criteria. Neurology 55:S40–S44PubMed
3.
go back to reference Biseul I, Sauleau P, Haegelen C, Trebon P, Drapier D, Raoul S, Drapier S, Lallement F, Rivier I, Lajat Y, Verin M (2005) Fear recognition is impaired by subthalamic nucleus stimulation in Parkinson’s disease. Neuropsychologia 43:1054–1059CrossRefPubMed Biseul I, Sauleau P, Haegelen C, Trebon P, Drapier D, Raoul S, Drapier S, Lallement F, Rivier I, Lajat Y, Verin M (2005) Fear recognition is impaired by subthalamic nucleus stimulation in Parkinson’s disease. Neuropsychologia 43:1054–1059CrossRefPubMed
4.
go back to reference Boussion N, Houzard C, Ostrowsky K, Ryvlin P, Mauguiere F, Cinotti L (2002) Automated detection of local normalization areas for ictal-interictal subtraction brain SPECT. J Nucl Med 43:1419–1425PubMed Boussion N, Houzard C, Ostrowsky K, Ryvlin P, Mauguiere F, Cinotti L (2002) Automated detection of local normalization areas for ictal-interictal subtraction brain SPECT. J Nucl Med 43:1419–1425PubMed
5.
go back to reference Cardebat D, Doyon B, Puel M, Goulet P, Joanette Y (1990) Evocation lexicale formelle et sémantique chez des sujets normaux: performances et dynamiques de production en fonction du sexe, de l’âge et du niveau d’étude. Acta Neurol Belg 90:207–217PubMed Cardebat D, Doyon B, Puel M, Goulet P, Joanette Y (1990) Evocation lexicale formelle et sémantique chez des sujets normaux: performances et dynamiques de production en fonction du sexe, de l’âge et du niveau d’étude. Acta Neurol Belg 90:207–217PubMed
6.
go back to reference Chang LT (1978) A method for attenuation correction in radionuclide computed tomography. IEEE Trans Nucl Sci 25:638–643CrossRef Chang LT (1978) A method for attenuation correction in radionuclide computed tomography. IEEE Trans Nucl Sci 25:638–643CrossRef
7.
go back to reference Chudasama Y, Baunez C, Robbins TW (2003) Functional disconnection of the medial prefrontal cortex and subthalamic nucleus in attentional performance: evidence of corticosubthalamic interaction. J Neurosci 23:5477–5485PubMed Chudasama Y, Baunez C, Robbins TW (2003) Functional disconnection of the medial prefrontal cortex and subthalamic nucleus in attentional performance: evidence of corticosubthalamic interaction. J Neurosci 23:5477–5485PubMed
8.
go back to reference Collins DL, Neelin P, Peters TM, Evans AC (1994) Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space. J Comput Assist Tomogr 18:192–205CrossRefPubMed Collins DL, Neelin P, Peters TM, Evans AC (1994) Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space. J Comput Assist Tomogr 18:192–205CrossRefPubMed
9.
go back to reference Darbaky Y, Baunez C, Arecchi P, Le Gallet E, Apicella P (2005) Reward-related neuronal activity in the subthalamic nucleus of the monkey. Neuroreport 16:1241–1244CrossRefPubMed Darbaky Y, Baunez C, Arecchi P, Le Gallet E, Apicella P (2005) Reward-related neuronal activity in the subthalamic nucleus of the monkey. Neuroreport 16:1241–1244CrossRefPubMed
10.
go back to reference Drapier D, Drapier S, Sauleau P, Haegelen C, Raoul S, Biseul I, Péron J, Lallement F, Rivier I, Reymann JM, Edan G, Verin M, Millet B (2006) Does subthalamic nucleus stimulation induce apathy in Parkinson’s disease? J Neurol 253:1083–1091CrossRefPubMed Drapier D, Drapier S, Sauleau P, Haegelen C, Raoul S, Biseul I, Péron J, Lallement F, Rivier I, Reymann JM, Edan G, Verin M, Millet B (2006) Does subthalamic nucleus stimulation induce apathy in Parkinson’s disease? J Neurol 253:1083–1091CrossRefPubMed
11.
go back to reference Drapier D, Péron J, Leray E, Sauleau P, Biseul I, Drapier S, Le Jeune F, Travers D, Bourguignon A, Haegelen C, Millet B, Verin M (2008) Emotion recognition impairment and apathy after subthalamic nucleus stimulation in Parkinson’s disease have separate neural substrates. Neuropsychologia 46:2796–2801CrossRefPubMed Drapier D, Péron J, Leray E, Sauleau P, Biseul I, Drapier S, Le Jeune F, Travers D, Bourguignon A, Haegelen C, Millet B, Verin M (2008) Emotion recognition impairment and apathy after subthalamic nucleus stimulation in Parkinson’s disease have separate neural substrates. Neuropsychologia 46:2796–2801CrossRefPubMed
12.
go back to reference Dujardin K, Defebvre L, Krystkowiak P, Blond S, Destee A (2001) Influence of chronic bilateral stimulation of subthalamic nucleus on cognitive function in Parkinson’s disease. J Neurol 248:603–611CrossRefPubMed Dujardin K, Defebvre L, Krystkowiak P, Blond S, Destee A (2001) Influence of chronic bilateral stimulation of subthalamic nucleus on cognitive function in Parkinson’s disease. J Neurol 248:603–611CrossRefPubMed
13.
go back to reference Dujardin K, Blairy S, Defebvre L, Krystkowiak P, Hess U, Blond S, Destee A (2004) Subthalamic nucleus stimulation induces deficits in decoding emotional facial expressions in Parkinson’s disease. J Neurol Neurosurg Psychiatry 75:202–208PubMed Dujardin K, Blairy S, Defebvre L, Krystkowiak P, Hess U, Blond S, Destee A (2004) Subthalamic nucleus stimulation induces deficits in decoding emotional facial expressions in Parkinson’s disease. J Neurol Neurosurg Psychiatry 75:202–208PubMed
14.
go back to reference Duvernoy HM (1991) The human brain. Surface, three-dimensional sectional anatomy and MRI. Springer, Vienna Duvernoy HM (1991) The human brain. Surface, three-dimensional sectional anatomy and MRI. Springer, Vienna
15.
go back to reference Ekman P, Friesen W (1976) Pictures of facial affect. Consulting Psychologists Press, Palo Alto Ekman P, Friesen W (1976) Pictures of facial affect. Consulting Psychologists Press, Palo Alto
16.
go back to reference Fahn S, Elton RL (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Goldstein M, Calne DB (eds) Recent developments in Parkinson’s disease, vol 2. Macmillan, New York, pp 153–163 Fahn S, Elton RL (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Goldstein M, Calne DB (eds) Recent developments in Parkinson’s disease, vol 2. Macmillan, New York, pp 153–163
17.
go back to reference Frouin V, Comtat C, Reilhac A, Gregoire MC (2002) Correction of partial-volume effect of PET striatal imaging: fast implementation and study of robustness. J Nucl Med 43:1715–1726PubMed Frouin V, Comtat C, Reilhac A, Gregoire MC (2002) Correction of partial-volume effect of PET striatal imaging: fast implementation and study of robustness. J Nucl Med 43:1715–1726PubMed
18.
go back to reference Grova C, Biraben A, Scarabin JM, Jannin P, Buvat I, Benali I, Gibaud B (2001) A methodology to validate MRI/SPECT registration methods using realistic SPECT simulated data. In: Proceedings of Medical Image Computing and Computer Assisted Interventions (MICCAI), Lectures Notes in Computer Science (LNCS) 2208:275–282 Grova C, Biraben A, Scarabin JM, Jannin P, Buvat I, Benali I, Gibaud B (2001) A methodology to validate MRI/SPECT registration methods using realistic SPECT simulated data. In: Proceedings of Medical Image Computing and Computer Assisted Interventions (MICCAI), Lectures Notes in Computer Science (LNCS) 2208:275–282
19.
go back to reference Grova C, Aubert-Broche B, Reilhac A, Gibaud B (2004) Evaluation of partial volume correction for FDG PET and perfusion SPECT data. In: IEEE Nuclear Science Symposium and Medical Imaging Conference Grova C, Aubert-Broche B, Reilhac A, Gibaud B (2004) Evaluation of partial volume correction for FDG PET and perfusion SPECT data. In: IEEE Nuclear Science Symposium and Medical Imaging Conference
20.
go back to reference Haegelen C, Verin M, Aubert-Broche B, Prigent F, Jannin P, Gibaud B, Morandi X (2005) Does subthalamic nucleus stimulation affect the frontal limbic areas? A SPECT study using a manual anatomical segmentation method. Surg Radiol Anat 14:1–6 Haegelen C, Verin M, Aubert-Broche B, Prigent F, Jannin P, Gibaud B, Morandi X (2005) Does subthalamic nucleus stimulation affect the frontal limbic areas? A SPECT study using a manual anatomical segmentation method. Surg Radiol Anat 14:1–6
21.
go back to reference Haegelen C, Rouaud T, Darnault P, Morandi X (2009) The subthalamic nucleus is a key-structure of limbic basal-ganglia functions. Med Hypoth 72:421–426CrossRef Haegelen C, Rouaud T, Darnault P, Morandi X (2009) The subthalamic nucleus is a key-structure of limbic basal-ganglia functions. Med Hypoth 72:421–426CrossRef
22.
go back to reference Hilker R, Voges J, Thiel A, Ghaemi M, Kerholz K, Sturm V, Heiss WD (2002) Deep brain stimulation of the subthalamic nucleus versus levodopa challenge in Parkinson’s disease: measuring the on- and off-conditions with FDG-PET. J Neural Transm 109:1257–1264CrossRefPubMed Hilker R, Voges J, Thiel A, Ghaemi M, Kerholz K, Sturm V, Heiss WD (2002) Deep brain stimulation of the subthalamic nucleus versus levodopa challenge in Parkinson’s disease: measuring the on- and off-conditions with FDG-PET. J Neural Transm 109:1257–1264CrossRefPubMed
23.
go back to reference Hilker R, Voges J, Weisenbach S, Kalbe E, Burghaus L, Ghaemi M, Lehrke R, Koulousakis A, Herholz K, Sturm V, Heiss WD (2003) Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson’s disease. J Cereb Blood Flow Metab 24:7–16 Hilker R, Voges J, Weisenbach S, Kalbe E, Burghaus L, Ghaemi M, Lehrke R, Koulousakis A, Herholz K, Sturm V, Heiss WD (2003) Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson’s disease. J Cereb Blood Flow Metab 24:7–16
24.
go back to reference Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442PubMed Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442PubMed
25.
go back to reference Langston JW, Widner H, Goetz CG, Brooks D, Fahn S, Freeman T, Watts R (1992) Core assessment program for intracerebral transplantation (CAPIT). Mov Disord 7:2–13CrossRefPubMed Langston JW, Widner H, Goetz CG, Brooks D, Fahn S, Freeman T, Watts R (1992) Core assessment program for intracerebral transplantation (CAPIT). Mov Disord 7:2–13CrossRefPubMed
26.
go back to reference Le Jeune F, Péron J, Biseul I, Fournier S, Sauleau P, Drapier S, Haegelen C, Drapier D, Millet B, Garin E, Herry JY, Malbert CH, Vérin M (2008) Subthalamic nucleus stimulation affects orbitofrontal cortex in facial emotion recognition: a PET study. Brain 131:1599–1608CrossRefPubMed Le Jeune F, Péron J, Biseul I, Fournier S, Sauleau P, Drapier S, Haegelen C, Drapier D, Millet B, Garin E, Herry JY, Malbert CH, Vérin M (2008) Subthalamic nucleus stimulation affects orbitofrontal cortex in facial emotion recognition: a PET study. Brain 131:1599–1608CrossRefPubMed
27.
go back to reference Krack P, Batir A, Van Blercom N, Chabardes S, Fraix V, Ardouin C, Koudsie A, Limousin PD, Benazzouz A, Le Bas JF, Benabid AL, Pollak P (2003) Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 349:1925–1934CrossRefPubMed Krack P, Batir A, Van Blercom N, Chabardes S, Fraix V, Ardouin C, Koudsie A, Limousin PD, Benazzouz A, Le Bas JF, Benabid AL, Pollak P (2003) Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 349:1925–1934CrossRefPubMed
28.
go back to reference Maurice N, Deniau JM, Glowinski J, Thierry AM (1998) Relationships between the prefrontal cortex and the basal ganglia in the rat: physiology of the corticosubthalamic circuits. J Neurosci 18:9539–9546PubMed Maurice N, Deniau JM, Glowinski J, Thierry AM (1998) Relationships between the prefrontal cortex and the basal ganglia in the rat: physiology of the corticosubthalamic circuits. J Neurosci 18:9539–9546PubMed
29.
go back to reference Maurice N, Deniau JM, Menetrey A, Glowinski J, Thierry AM (1998) Prefrontal cortex-basal ganglia circuits in the rat: involvement of ventral pallidum and subthalamic nucleus. Synapse 29:363–370CrossRefPubMed Maurice N, Deniau JM, Menetrey A, Glowinski J, Thierry AM (1998) Prefrontal cortex-basal ganglia circuits in the rat: involvement of ventral pallidum and subthalamic nucleus. Synapse 29:363–370CrossRefPubMed
30.
go back to reference Maurice N, Deniau JM, Glowinski J, Thierry AM (1999) Relationships between the prefrontal cortex and the basal ganglia in the rat: physiology of the corticonigral circuits. J Neurosci 19:4671–4681 Maurice N, Deniau JM, Glowinski J, Thierry AM (1999) Relationships between the prefrontal cortex and the basal ganglia in the rat: physiology of the corticonigral circuits. J Neurosci 19:4671–4681
31.
go back to reference Mattis S (1988) Dementia rating scale. Psychological Assessment Resources, Odessa Mattis S (1988) Dementia rating scale. Psychological Assessment Resources, Odessa
32.
go back to reference Nelson HE (1976) A modified card sorting test sensitive to frontal lobe defects. Cortex 12:313–324PubMed Nelson HE (1976) A modified card sorting test sensitive to frontal lobe defects. Cortex 12:313–324PubMed
33.
go back to reference Ono M, Kubik S, Abernathey CD (1990) Atlas of the cerebral sulci. Georg Thieme Verlag, Stuttgart Ono M, Kubik S, Abernathey CD (1990) Atlas of the cerebral sulci. Georg Thieme Verlag, Stuttgart
34.
go back to reference Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop. Brain Res Rev 20:91–127CrossRefPubMed Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop. Brain Res Rev 20:91–127CrossRefPubMed
35.
go back to reference Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Rev 20:128–154CrossRefPubMed Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Rev 20:128–154CrossRefPubMed
36.
go back to reference Parent A (1996) Carpenter’s human neuroanatomy. Williams & Wilkins, Media Parent A (1996) Carpenter’s human neuroanatomy. Williams & Wilkins, Media
37.
go back to reference Parsons TD, Rogers SA, Braayen AJ, Woods SP, Troster AI (2006) Cognitive sequelae of subthalamic nucleus deep brain stimulation in Parkinson’s disease: a meta-analysis. Lancet Neurol 5:578–588CrossRefPubMed Parsons TD, Rogers SA, Braayen AJ, Woods SP, Troster AI (2006) Cognitive sequelae of subthalamic nucleus deep brain stimulation in Parkinson’s disease: a meta-analysis. Lancet Neurol 5:578–588CrossRefPubMed
38.
go back to reference Reitan RM (1958) Validity of the trail making test as an indication of organic brain damage. Percept Mot Skills 8:271–276CrossRef Reitan RM (1958) Validity of the trail making test as an indication of organic brain damage. Percept Mot Skills 8:271–276CrossRef
39.
go back to reference Romanelli P, Heit G, Bruce C, Kraus A, Hastie T, Bronte-Stewart HM (2004) Microelectrode recording revealing a somatotopic body map in the subthalamic nucleus in humans with Parkinson disease. J Neurosurg 100:611–618CrossRefPubMed Romanelli P, Heit G, Bruce C, Kraus A, Hastie T, Bronte-Stewart HM (2004) Microelectrode recording revealing a somatotopic body map in the subthalamic nucleus in humans with Parkinson disease. J Neurosurg 100:611–618CrossRefPubMed
40.
go back to reference Sauleau P, Raoul S, Lallement F, Rivier I, Drapier S, Lajat Y, Verin M (2005) Motor and non motor effects during intraoperative subthalamic stimulation for Parkinson’s disease. J Neurol 252:457–464CrossRefPubMed Sauleau P, Raoul S, Lallement F, Rivier I, Drapier S, Lajat Y, Verin M (2005) Motor and non motor effects during intraoperative subthalamic stimulation for Parkinson’s disease. J Neurol 252:457–464CrossRefPubMed
41.
go back to reference Schroeder U, Kuehler A, Haslinger B, Erhard P, Fogel W, Tronnier VM, Lange KW, Boecker H, Ceballos-Baumann AO (2002) Subthalamic nucleus stimulation affects striato-anterior cingulate cortex circuit in a response conflict task: a PET study. Brain 125:1995–2004CrossRefPubMed Schroeder U, Kuehler A, Haslinger B, Erhard P, Fogel W, Tronnier VM, Lange KW, Boecker H, Ceballos-Baumann AO (2002) Subthalamic nucleus stimulation affects striato-anterior cingulate cortex circuit in a response conflict task: a PET study. Brain 125:1995–2004CrossRefPubMed
42.
go back to reference Schroeder U, Kuehler A, Lange KW, Haslinger B, Tronnier VM, Krause M, Pfister R, Boecker H, Ceballos-Baumann AO (2003) Subthalamic nucleus stimulation affects a frontotemporal network: a PET study. Ann Neurol 54:445–450CrossRefPubMed Schroeder U, Kuehler A, Lange KW, Haslinger B, Tronnier VM, Krause M, Pfister R, Boecker H, Ceballos-Baumann AO (2003) Subthalamic nucleus stimulation affects a frontotemporal network: a PET study. Ann Neurol 54:445–450CrossRefPubMed
43.
go back to reference Schroeder U, Kuelher A, Hennenlotter A, Haslinger B, Tronnier VM, Krause M, Pfister R, Sprengelmeyer R, Lange KW, Ceballos-Baumann AO (2004) Facial expression recognition and subthalamic nucleus stimulation. J Neurol Neurosurg Psychiatry 75:648–650CrossRefPubMed Schroeder U, Kuelher A, Hennenlotter A, Haslinger B, Tronnier VM, Krause M, Pfister R, Sprengelmeyer R, Lange KW, Ceballos-Baumann AO (2004) Facial expression recognition and subthalamic nucleus stimulation. J Neurol Neurosurg Psychiatry 75:648–650CrossRefPubMed
44.
go back to reference Stroop JR (1935) Studies of interference in serial verbal reactions. J Exp Psych 18:643–662CrossRef Stroop JR (1935) Studies of interference in serial verbal reactions. J Exp Psych 18:643–662CrossRef
45.
go back to reference Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain. Georg Thieme Verlag, Stuttgart Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain. Georg Thieme Verlag, Stuttgart
46.
go back to reference Temel Y, Kessels A, Tan S, Topdag A, Boon P, Visser-Vandewalle V (2006) Behavioural changes after bilateral subthalamic stimulation in advanced Parkinson disease: a systematic review. Parkinsonism Relat Disord 12:265–272CrossRefPubMed Temel Y, Kessels A, Tan S, Topdag A, Boon P, Visser-Vandewalle V (2006) Behavioural changes after bilateral subthalamic stimulation in advanced Parkinson disease: a systematic review. Parkinsonism Relat Disord 12:265–272CrossRefPubMed
47.
go back to reference Wichmann T, DeLong MR (1996) Functional and pathophysiological models of the basal ganglia. Curr Opin Neurobiol 6:751–758CrossRefPubMed Wichmann T, DeLong MR (1996) Functional and pathophysiological models of the basal ganglia. Curr Opin Neurobiol 6:751–758CrossRefPubMed
Metadata
Title
SPECT and PET analysis of subthalamic stimulation in Parkinson’s disease: analysis using a manual segmentation
Authors
Claire Haegelen
Daniel García-Lorenzo
Florence Le Jeune
Julie Péron
Bernard Gibaud
Laurent Riffaud
Gilles Brassier
Christian Barillot
Marc Vérin
Xavier Morandi
Publication date
01-03-2010
Publisher
Springer-Verlag
Published in
Journal of Neurology / Issue 3/2010
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-009-5327-8

Other articles of this Issue 3/2010

Journal of Neurology 3/2010 Go to the issue