Skip to main content
Erschienen in: Neuroradiology 3/2020

18.12.2019 | Paediatric Neuroradiology

Children with epilepsy demonstrate macro- and microstructural changes in the thalamus, putamen, and amygdala

verfasst von: Sarah J. MacEachern, Jonathan D. Santoro, Kara J. Hahn, Zachary A. Medress, Ximena Stecher, Matthew D. Li, Jin S. Hahn, Kristen W. Yeom, Nils D. Forkert

Erschienen in: Neuroradiology | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Despite evidence for macrostructural alteration in epilepsy patients later in life, little is known about the underlying pathological or compensatory mechanisms at younger ages causing these alterations. The aim of this work was to investigate the impact of pediatric epilepsy on the central nervous system, including gray matter volume, cerebral blood flow, and water diffusion, compared with neurologically normal children.

Methods

Inter-ictal magnetic resonance imaging data was obtained from 30 children with epilepsy ages 1–16 (73% F, 27% M). An atlas-based approach was used to determine values for volume, cerebral blood flow, and apparent diffusion coefficient in the cerebral cortex, hippocampus, thalamus, caudate, putamen, globus pallidus, amygdala, and nucleus accumbens. These values were then compared with previously published values from 100 neurologically normal children using a MANCOVA analysis.

Results

Most brain volumes of children with epilepsy followed a pattern similar to typically developing children, except for significantly larger putamen and amygdala. Cerebral blood flow was also comparable between the groups, except for the putamen, which demonstrated decreased blood flow in children with epilepsy. Diffusion (apparent diffusion coefficient) showed a trend towards higher values in children with epilepsy, with significantly elevated diffusion within the thalamus in children with epilepsy compared with neurologically normal children.

Conclusion

Children with epilepsy show statistically significant differences in volume, diffusion, and cerebral blood flow within their thalamus, putamen, and amygdala, suggesting that epilepsy is associated with structural changes of the central nervous system influencing brain development and potentially leading to poorer neurocognitive outcomes.
Literatur
1.
2.
Zurück zum Zitat Hauser WA, Annegers JF, Kurland LT (1993) Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935-1984. Epilepsia 34:453–468PubMed Hauser WA, Annegers JF, Kurland LT (1993) Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935-1984. Epilepsia 34:453–468PubMed
3.
Zurück zum Zitat MacEachern SJ, D'Alfonso S, McDonald RJ et al (2017) Most children with epilepsy experience postictal phenomena, often preventing a return to normal activities of childhood. Pediatr Neurol 72(42–50):e43 MacEachern SJ, D'Alfonso S, McDonald RJ et al (2017) Most children with epilepsy experience postictal phenomena, often preventing a return to normal activities of childhood. Pediatr Neurol 72(42–50):e43
4.
Zurück zum Zitat Danguecan AN, Smith ML (2017) Academic outcomes in individuals with childhood-onset epilepsy: mediating effects of working memory. J Int Neuropsychol Soc:23(7):594–604PubMed Danguecan AN, Smith ML (2017) Academic outcomes in individuals with childhood-onset epilepsy: mediating effects of working memory. J Int Neuropsychol Soc:23(7):594–604PubMed
5.
Zurück zum Zitat Hamiwka LD, Wirrell EC (2009) Comorbidities in pediatric epilepsy: beyond “just” treating the seizures. J Child Neurol 24:734–742PubMed Hamiwka LD, Wirrell EC (2009) Comorbidities in pediatric epilepsy: beyond “just” treating the seizures. J Child Neurol 24:734–742PubMed
6.
Zurück zum Zitat Ottman R, Lipton RB, Ettinger AB, Cramer JA, Reed ML, Morrison A, Wan GJ (2011) Comorbidities of epilepsy: results from the epilepsy comorbidities and health (EPIC) survey. Epilepsia 52:308–315PubMed Ottman R, Lipton RB, Ettinger AB, Cramer JA, Reed ML, Morrison A, Wan GJ (2011) Comorbidities of epilepsy: results from the epilepsy comorbidities and health (EPIC) survey. Epilepsia 52:308–315PubMed
7.
Zurück zum Zitat Berg AT, Baca CB, Rychlik K et al (2016) Determinants of social outcomes in adults with childhood-onset epilepsy. Pediatrics 137PubMedPubMedCentral Berg AT, Baca CB, Rychlik K et al (2016) Determinants of social outcomes in adults with childhood-onset epilepsy. Pediatrics 137PubMedPubMedCentral
8.
Zurück zum Zitat Gilmore JH, Lin W, Prastawa MW, Looney CB, Vetsa YS, Knickmeyer RC, Evans DD, Smith JK, Hamer RM, Lieberman JA, Gerig G (2007) Regional gray matter growth, sexual dimorphism, and cerebral asymmetry in the neonatal brain. J Neurosci 27:1255–1260PubMedPubMedCentral Gilmore JH, Lin W, Prastawa MW, Looney CB, Vetsa YS, Knickmeyer RC, Evans DD, Smith JK, Hamer RM, Lieberman JA, Gerig G (2007) Regional gray matter growth, sexual dimorphism, and cerebral asymmetry in the neonatal brain. J Neurosci 27:1255–1260PubMedPubMedCentral
9.
Zurück zum Zitat Knickmeyer RC, Gouttard S, Kang C et al (2008) A structural MRI study of human brain development from birth to 2 years. J Neurosci 28:12176–12182PubMedPubMedCentral Knickmeyer RC, Gouttard S, Kang C et al (2008) A structural MRI study of human brain development from birth to 2 years. J Neurosci 28:12176–12182PubMedPubMedCentral
10.
Zurück zum Zitat Sampaio RC, Truwit CL (2001) Myelination in the developing human brain. Handbook of developmental cognitive neuroscience:35–44 Sampaio RC, Truwit CL (2001) Myelination in the developing human brain. Handbook of developmental cognitive neuroscience:35–44
11.
Zurück zum Zitat Forkert ND, Li MD, Lober RM, Yeom KW (2016) Gray matter growth is accompanied by increasing blood flow and decreasing apparent diffusion coefficient during childhood. AJNR Am J Neuroradiol 37:1738–1744PubMed Forkert ND, Li MD, Lober RM, Yeom KW (2016) Gray matter growth is accompanied by increasing blood flow and decreasing apparent diffusion coefficient during childhood. AJNR Am J Neuroradiol 37:1738–1744PubMed
12.
Zurück zum Zitat Holmes GL, Ben-Ari Y (2001) The neurobiology and consequences of epilepsy in the developing brain. Pediatr Res 49:320–325PubMed Holmes GL, Ben-Ari Y (2001) The neurobiology and consequences of epilepsy in the developing brain. Pediatr Res 49:320–325PubMed
13.
Zurück zum Zitat Lee JH, Kim SE, Park CH et al (2015) Gray and white matter volumes and cognitive dysfunction in drug-naive newly diagnosed pediatric epilepsy. Biomed Res Int 2015:923861PubMedPubMedCentral Lee JH, Kim SE, Park CH et al (2015) Gray and white matter volumes and cognitive dysfunction in drug-naive newly diagnosed pediatric epilepsy. Biomed Res Int 2015:923861PubMedPubMedCentral
14.
Zurück zum Zitat O'Muircheartaigh J, Vollmar C, Barker GJ, Kumari V, Symms MR, Thompson P, Duncan JS, Koepp MJ, Richardson MP (2011) Focal structural changes and cognitive dysfunction in juvenile myoclonic epilepsy. Neurology 76:34–40PubMedPubMedCentral O'Muircheartaigh J, Vollmar C, Barker GJ, Kumari V, Symms MR, Thompson P, Duncan JS, Koepp MJ, Richardson MP (2011) Focal structural changes and cognitive dysfunction in juvenile myoclonic epilepsy. Neurology 76:34–40PubMedPubMedCentral
15.
Zurück zum Zitat Overvliet GM, Besseling RM, Jansen JF et al (2013) Early onset of cortical thinning in children with rolandic epilepsy. Neuroimage Clin 2:434–439PubMedPubMedCentral Overvliet GM, Besseling RM, Jansen JF et al (2013) Early onset of cortical thinning in children with rolandic epilepsy. Neuroimage Clin 2:434–439PubMedPubMedCentral
16.
Zurück zum Zitat Baram TZ (2012) The brain, seizures and epilepsy throughout life: understanding a moving target. Epilepsy Curr 12:7–12PubMedPubMedCentral Baram TZ (2012) The brain, seizures and epilepsy throughout life: understanding a moving target. Epilepsy Curr 12:7–12PubMedPubMedCentral
17.
Zurück zum Zitat Nuyts S, D'Souza W, Bowden SC, Vogrin SJ (2017) Structural brain abnormalities in genetic generalized epilepsies: a systematic review and meta-analysis. Epilepsia 58:2025–2037PubMed Nuyts S, D'Souza W, Bowden SC, Vogrin SJ (2017) Structural brain abnormalities in genetic generalized epilepsies: a systematic review and meta-analysis. Epilepsia 58:2025–2037PubMed
18.
Zurück zum Zitat Whelan CD, Altmann A, Botia JA et al (2018) Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study. Brain 141:391–408PubMedPubMedCentral Whelan CD, Altmann A, Botia JA et al (2018) Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study. Brain 141:391–408PubMedPubMedCentral
19.
Zurück zum Zitat Kimiwada T, Juhasz C, Makki M et al (2006) Hippocampal and thalamic diffusion abnormalities in children with temporal lobe epilepsy. Epilepsia 47:167–175PubMed Kimiwada T, Juhasz C, Makki M et al (2006) Hippocampal and thalamic diffusion abnormalities in children with temporal lobe epilepsy. Epilepsia 47:167–175PubMed
20.
Zurück zum Zitat Keller SS, Ahrens T, Mohammadi S, Möddel G, Kugel H, Ringelstein EB, Deppe M (2011) Microstructural and volumetric abnormalities of the putamen in juvenile myoclonic epilepsy. Epilepsia 52:1715–1724PubMed Keller SS, Ahrens T, Mohammadi S, Möddel G, Kugel H, Ringelstein EB, Deppe M (2011) Microstructural and volumetric abnormalities of the putamen in juvenile myoclonic epilepsy. Epilepsia 52:1715–1724PubMed
21.
Zurück zum Zitat Nehlig A, Vergnes M, Waydelich R, Hirsch E, Charbonne R, Marescaux C, Seylaz J (1996) Absence seizures induce a decrease in cerebral blood flow: human and animal data. J Cereb Blood Flow Metab 16:147–155PubMed Nehlig A, Vergnes M, Waydelich R, Hirsch E, Charbonne R, Marescaux C, Seylaz J (1996) Absence seizures induce a decrease in cerebral blood flow: human and animal data. J Cereb Blood Flow Metab 16:147–155PubMed
22.
Zurück zum Zitat Le Bihan D (2013) Apparent diffusion coefficient and beyond: what diffusion MR imaging can tell us about tissue structure. Radiology 268:318–322PubMed Le Bihan D (2013) Apparent diffusion coefficient and beyond: what diffusion MR imaging can tell us about tissue structure. Radiology 268:318–322PubMed
23.
Zurück zum Zitat Le Bihan D, Johansen-Berg H (2012) Diffusion MRI at 25: exploring brain tissue structure and function. Neuroimage 61:324–341PubMed Le Bihan D, Johansen-Berg H (2012) Diffusion MRI at 25: exploring brain tissue structure and function. Neuroimage 61:324–341PubMed
24.
Zurück zum Zitat Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, Lagae L, Moshé SL, Peltola J, Roulet Perez E, Scheffer IE, Zuberi SM (2017) Operational classification of seizure types by the international league against epilepsy: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 58:522–530PubMed Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, Lagae L, Moshé SL, Peltola J, Roulet Perez E, Scheffer IE, Zuberi SM (2017) Operational classification of seizure types by the international league against epilepsy: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 58:522–530PubMed
25.
Zurück zum Zitat Dai W, Garcia D, de Bazelaire C, Alsop DC (2008) Continuous flow-driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields. Magn Reson Med 60:1488–1497PubMedPubMedCentral Dai W, Garcia D, de Bazelaire C, Alsop DC (2008) Continuous flow-driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields. Magn Reson Med 60:1488–1497PubMedPubMedCentral
26.
Zurück zum Zitat Buxton RB, Frank LR, Wong EC, Siewert B, Warach S, Edelman RR (1998) A general kinetic model for quantitative perfusion imaging with arterial spin labeling. Magn Reson Med 40:383–396PubMed Buxton RB, Frank LR, Wong EC, Siewert B, Warach S, Edelman RR (1998) A general kinetic model for quantitative perfusion imaging with arterial spin labeling. Magn Reson Med 40:383–396PubMed
27.
Zurück zum Zitat Li MD, Forkert ND, Kundu P et al (2017) Brain perfusion and diffusion abnormalities in children treated for posterior fossa brain tumors. J Pediatr 185:173–180PubMed Li MD, Forkert ND, Kundu P et al (2017) Brain perfusion and diffusion abnormalities in children treated for posterior fossa brain tumors. J Pediatr 185:173–180PubMed
28.
Zurück zum Zitat Stejskal E, Tanner J (1965) Spin diffusion measurements: spin echoes in the presence of a time-dependent field gradient. J Chem Phys 42:288–292 Stejskal E, Tanner J (1965) Spin diffusion measurements: spin echoes in the presence of a time-dependent field gradient. J Chem Phys 42:288–292
29.
Zurück zum Zitat Mazziotta J, Toga A, Evans A et al (2001) A probabilistic atlas and reference system for the human brain: international consortium for brain mapping (ICBM). Philos Trans R Soc Lond Ser B Biol Sci 356:1293–1322 Mazziotta J, Toga A, Evans A et al (2001) A probabilistic atlas and reference system for the human brain: international consortium for brain mapping (ICBM). Philos Trans R Soc Lond Ser B Biol Sci 356:1293–1322
30.
Zurück zum Zitat Sakov A, Golani I, Lipkind D et al (2010) High-throughput data analysis in behavior genetics. Ann Appl Stat 4:743–763 Sakov A, Golani I, Lipkind D et al (2010) High-throughput data analysis in behavior genetics. Ann Appl Stat 4:743–763
31.
Zurück zum Zitat Chilla GS, Tan CH, Xu C, Poh CL (2015) Diffusion weighted magnetic resonance imaging and its recent trend-a survey. Quant Imaging Med Surg 5:407–422PubMedPubMedCentral Chilla GS, Tan CH, Xu C, Poh CL (2015) Diffusion weighted magnetic resonance imaging and its recent trend-a survey. Quant Imaging Med Surg 5:407–422PubMedPubMedCentral
32.
Zurück zum Zitat Haykin M, Gorman M, van Hoff J et al (2006) Diffusion-weighted MRI correlates of subacute methotrexate-related neurotoxicity. J Neuro-Oncol 76:153–157 Haykin M, Gorman M, van Hoff J et al (2006) Diffusion-weighted MRI correlates of subacute methotrexate-related neurotoxicity. J Neuro-Oncol 76:153–157
33.
Zurück zum Zitat Zhang L, Ravdin LD, Relkin N, Zimmerman RD, Jordan B, Lathan WE, Uluğ AM (2003) Increased diffusion in the brain of professional boxers: a preclinical sign of traumatic brain injury? AJNR Am J Neuroradiol 24:52–57PubMed Zhang L, Ravdin LD, Relkin N, Zimmerman RD, Jordan B, Lathan WE, Uluğ AM (2003) Increased diffusion in the brain of professional boxers: a preclinical sign of traumatic brain injury? AJNR Am J Neuroradiol 24:52–57PubMed
34.
Zurück zum Zitat Chappell MH, Ulug AM, Zhang L et al (2006) Distribution of microstructural damage in the brains of professional boxers: a diffusion MRI study. J Magn Reson Imaging 24:537–542PubMed Chappell MH, Ulug AM, Zhang L et al (2006) Distribution of microstructural damage in the brains of professional boxers: a diffusion MRI study. J Magn Reson Imaging 24:537–542PubMed
35.
Zurück zum Zitat Baliyan V, Das CJ, Sharma R et al (2016) Diffusion weighted imaging: technique and applications. World J Radiol 8:785–798PubMedPubMedCentral Baliyan V, Das CJ, Sharma R et al (2016) Diffusion weighted imaging: technique and applications. World J Radiol 8:785–798PubMedPubMedCentral
36.
Zurück zum Zitat Sherman SM (2016) Thalamus plays a central role in ongoing cortical functioning. Nat Neurosci 19:533–541PubMed Sherman SM (2016) Thalamus plays a central role in ongoing cortical functioning. Nat Neurosci 19:533–541PubMed
37.
Zurück zum Zitat Steriade M, Llinas RR (1988) The functional states of the thalamus and the associated neuronal interplay. Physiol Rev 68:649–742PubMed Steriade M, Llinas RR (1988) The functional states of the thalamus and the associated neuronal interplay. Physiol Rev 68:649–742PubMed
38.
Zurück zum Zitat Timofeev I, Steriade M (2004) Neocortical seizures: initiation, development and cessation. Neuroscience 123:299–336PubMed Timofeev I, Steriade M (2004) Neocortical seizures: initiation, development and cessation. Neuroscience 123:299–336PubMed
39.
Zurück zum Zitat Blumenfeld H (2005) Cellular and network mechanisms of spike-wave seizures. Epilepsia 46(Suppl 9):21–33PubMed Blumenfeld H (2005) Cellular and network mechanisms of spike-wave seizures. Epilepsia 46(Suppl 9):21–33PubMed
40.
Zurück zum Zitat Futatsugi Y, Riviello JJ Jr (1998) Mechanisms of generalized absence epilepsy. Brain and Development 20:75–79PubMed Futatsugi Y, Riviello JJ Jr (1998) Mechanisms of generalized absence epilepsy. Brain and Development 20:75–79PubMed
41.
Zurück zum Zitat Blumenfeld H (2003) From molecules to networks: cortical/subcortical interactions in the pathophysiology of idiopathic generalized epilepsy. Epilepsia 44(Suppl 2):7–15PubMed Blumenfeld H (2003) From molecules to networks: cortical/subcortical interactions in the pathophysiology of idiopathic generalized epilepsy. Epilepsia 44(Suppl 2):7–15PubMed
42.
Zurück zum Zitat Blumenfeld H (2014) What is a seizure network? Long-range network consequences of focal seizures. Adv Exp Med Biol 813:63–70PubMedPubMedCentral Blumenfeld H (2014) What is a seizure network? Long-range network consequences of focal seizures. Adv Exp Med Biol 813:63–70PubMedPubMedCentral
43.
Zurück zum Zitat Nolan MA, Redoblado MA, Lah S, Sabaz M, Lawson JA, Cunningham AM, Bleasel AF, Bye AM (2004) Memory function in childhood epilepsy syndromes. J Paediatr Child Health 40:20–27PubMed Nolan MA, Redoblado MA, Lah S, Sabaz M, Lawson JA, Cunningham AM, Bleasel AF, Bye AM (2004) Memory function in childhood epilepsy syndromes. J Paediatr Child Health 40:20–27PubMed
45.
Zurück zum Zitat Lin JJ, Riley JD, Hsu DA, Stafstrom CE, Dabbs K, Becker T, Seidenberg M, Hermann BP (2012) Striatal hypertrophy and its cognitive effects in new-onset benign epilepsy with centrotemporal spikes. Epilepsia 53:677–685PubMedPubMedCentral Lin JJ, Riley JD, Hsu DA, Stafstrom CE, Dabbs K, Becker T, Seidenberg M, Hermann BP (2012) Striatal hypertrophy and its cognitive effects in new-onset benign epilepsy with centrotemporal spikes. Epilepsia 53:677–685PubMedPubMedCentral
46.
47.
Zurück zum Zitat Bower SP, Vogrin SJ, Morris K et al (2003) Amygdala volumetry in “imaging-negative” temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 74:1245–1249PubMedPubMedCentral Bower SP, Vogrin SJ, Morris K et al (2003) Amygdala volumetry in “imaging-negative” temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 74:1245–1249PubMedPubMedCentral
48.
Zurück zum Zitat Lv RJ, Sun ZR, Cui T et al (2014) Temporal lobe epilepsy with amygdala enlargement: a subtype of temporal lobe epilepsy. BMC Neurol 14:194PubMedPubMedCentral Lv RJ, Sun ZR, Cui T et al (2014) Temporal lobe epilepsy with amygdala enlargement: a subtype of temporal lobe epilepsy. BMC Neurol 14:194PubMedPubMedCentral
49.
Zurück zum Zitat Joo EY, Hong SB, Tae WS, Han SJ, Seo DW, Lee KH, Lee MH (2006) Effect of lamotrigine on cerebral blood flow in patients with idiopathic generalised epilepsy. Eur J Nucl Med Mol Imaging 33:724–729PubMed Joo EY, Hong SB, Tae WS, Han SJ, Seo DW, Lee KH, Lee MH (2006) Effect of lamotrigine on cerebral blood flow in patients with idiopathic generalised epilepsy. Eur J Nucl Med Mol Imaging 33:724–729PubMed
50.
Zurück zum Zitat Gaillard WD, Zeffiro T, Fazilat S, DeCarli C, Theodore WH (1996) Effect of valproate on cerebral metabolism and blood flow: an 18F-2-deoxyglucose and 15O water positron emission tomography study. Epilepsia 37:515–521PubMed Gaillard WD, Zeffiro T, Fazilat S, DeCarli C, Theodore WH (1996) Effect of valproate on cerebral metabolism and blood flow: an 18F-2-deoxyglucose and 15O water positron emission tomography study. Epilepsia 37:515–521PubMed
51.
Zurück zum Zitat Kaushal S, Tamer Z, Opoku F et al (2016) Anticonvulsant drug-induced cell death in the developing white matter of the rodent brain. Epilepsia 57:727–734PubMedPubMedCentral Kaushal S, Tamer Z, Opoku F et al (2016) Anticonvulsant drug-induced cell death in the developing white matter of the rodent brain. Epilepsia 57:727–734PubMedPubMedCentral
Metadaten
Titel
Children with epilepsy demonstrate macro- and microstructural changes in the thalamus, putamen, and amygdala
verfasst von
Sarah J. MacEachern
Jonathan D. Santoro
Kara J. Hahn
Zachary A. Medress
Ximena Stecher
Matthew D. Li
Jin S. Hahn
Kristen W. Yeom
Nils D. Forkert
Publikationsdatum
18.12.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Neuroradiology / Ausgabe 3/2020
Print ISSN: 0028-3940
Elektronische ISSN: 1432-1920
DOI
https://doi.org/10.1007/s00234-019-02332-8

Weitere Artikel der Ausgabe 3/2020

Neuroradiology 3/2020 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Was nützt die Kraniektomie bei schwerer tiefer Hirnblutung?

17.05.2024 Hirnblutung Nachrichten

Eine Studie zum Nutzen der druckentlastenden Kraniektomie nach schwerer tiefer supratentorieller Hirnblutung deutet einen Nutzen der Operation an. Für überlebende Patienten ist das dennoch nur eine bedingt gute Nachricht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.