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Volumetric study of brain MRI in a cohort of patients with neurotransmitter disorders

  • Paediatric Neuroradiology
  • Published:
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Abstract

Purpose

Inborn errors of neurotransmitters are rare monogenic diseases. In general, conventional neuroimaging is not useful for diagnosis. Nevertheless, advanced neuroimaging techniques could provide novel diagnosis and prognosis biomarkers. We aim to describe cerebral volumetric findings in a group of Spanish patients with neurotransmitter disorders.

Methods

Fifteen 3D T1-weighted brain images from the International Working Group on Neurotransmitter related Disorders Spanish cohort were assessed (eight with monoamine and seven with amino acid disorders). Volumes of cortical and subcortical brain structures were obtained for each patient and then compared with those of two healthy individuals matched by sex and age.

Results

Regardless of the underlying disease, patients showed a smaller total cerebral tissue volume, which was apparently associated with clinical severity. A characteristic volumetric deficit pattern, including the right Heschl gyrus and the bilateral occipital gyrus, was identified. In severe cases, a distinctive pattern comprised the middle and posterior portions of the right cingulate, the left superior motor area and the cerebellum. In succinate semialdehyde dehydrogenase deficiency, volumetric affection seems to worsen over life.

Conclusion

Despite the heterogeneity and limited size of our cohort, we found novel and relevant data. Total volume deficit appears to be a marker of severity, regardless of the specific neurotransmitter disease and irrespective of the information obtained from conventional neuroimaging. Volumetric assessment of individual brain structures could provide a deeper knowledge about pathophysiology, disease severity and specific clinical traits.

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Abbreviations

GABA:

Gamma-aminobutyric acid

CSF:

Cerebrospinal fluid

MRI:

Magnetic resonance imaging

iNTD:

International Working Group on Neurotransmitter related Disorders

AADCD:

Aromatic amino acid decarboxylase deficiency

ADGTPCHD:

Autosomal dominant GTP cyclohydrolase deficiency

ARGTPCHD:

Autosomal recessive GTP cyclohydrolase deficiency

MAOA-BD:

Monoamine oxidase A and B deficiency

NKH:

Non-ketotic hyperglycinemia

PTPSD:

6-Pyruvoyl-tetrahydropterin synthase deficiency

SSADHD:

Succinate-semialdehyde-dehydroxylase deficiency

THD:

Tyrosine hydroxylase deficiency

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Acknowledgements

We thank the patients and their parents for their support and participation in this study.

Funding

This work was supported by the FIS P118/00111 “Instituto de Salud Carlos III (ISCIII)” and “Fondo Europeo de desarrollo regional (FEDER)”.

Author information

Author notes

  1. Chiara Alfonsi and Christian Stephan-Otto contributed equally to this work.

Authors and Affiliations

  1. Inborn Errors of Metabolism Unit, Pediatric Neurology Department, Institut de Recerca Sant Joan de Déu, and MetabERN, Hospital Sant Joan de Déu, Passeig Sant Joan De Deu Nº 2, 08950, Esplugues De Llobregat, Barcelona, Spain

    Chiara Alfonsi, Natalia Juliá Palacios & Àngels Garcia-Cazorla

  2. Department of Human Neuroscience, Sapienza, University of Rome, Via dei Sabelli n.108, 00185, Rome, Italy

    Chiara Alfonsi

  3. Institut de Recerca Sant Joan de Déu, Pg Sant Joan De Deu Nº 2, 08950, Esplugues De Llobregat, Barcelona, Spain

    Christian Stephan-Otto

  4. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Av. Monforte de Lemos, 3-5. Pabellón 11. Planta 0, 28029, Madrid, Spain

    Christian Stephan-Otto

  5. Unit of Inherited Metabolic Diseases and Neuropediatrics, Hospital German Trias I Pujol, Carretera de Canyet s/n, 08916, Badalona, Spain

    Elisenda Cortès-Saladelafont

  6. Universitat Autònoma de Barcelona, Plaza Cívica, Bellaterra, Cerdanyola del Vallès, 08193, Barcelona, Spain

    Elisenda Cortès-Saladelafont & Inés Podzamczer-Valls

  7. Hospital de La Santa Creu I Sant Pau, Carrer de Sant Antoni Maria Claret n. 167, 08025, Barcelona, Spain

    Inés Podzamczer-Valls

  8. Department of Pediatrics, Hospital Universitario Severo Ochoa, Av. de Orellana s/n, 28911, Leganés, Spain

    Nuria Gutiérrez Cruz

  9. Department of Pediatric Neurology, Hospital Universitario Virgen de La Arrixaca, Ctra. Madrid-Cartagena s/n, 30120, El Palmar, Murcia, Murcia, Spain

    María Rosario Domingo Jiménez & Salvador Ibáñez Micó

  10. Department of Neurology, Hospital La Fe, Avinguda de Fernando Abril Martorell n.106, 46026, Valencia, Spain

    Miguel Tomás Vila

  11. Division of Child Neurology and Metabolic Disorders, University Children’s Hospital Heidelberg and MetabERN, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany

    Kathrin Jeltsch, Oya Kuseyri Hübschmann & Thomas Opladen

  12. Department of Pediatric Neurology, Hospital La Paz, C. de Pedro Rico n. 6, 28029, Madrid, Spain

    Ramón Velázquez Fragua

  13. Department of Psychiatry, Hospital General de Granollers, Carrer de Francesc Ribas s/n, 08402, Granollers, Spain

    Teresa Gómez & Oscar Alcoverro Fortuny

  14. Metabolic Disorders Unit, Hospital Universitario Miguel Servet, P.º Isabel La Católica, 1-3, 50009, Saragossa, Spain

    Inmaculada García Jiménez

  15. Pediatric Neurology Unit, Department of Pediatrics, University Hospital Reina Sofía, IMIBIC, Av. Menendez Pidal S/N, 14004, Córdoba, Spain

    Eduardo López Laso

  16. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), C. de Melchor Fernández Almagro n. 3, 28029, Madrid, Spain

    Eduardo López Laso & Àngels Garcia-Cazorla

  17. Department of Pediatrics, Hospital Parc Tauli, Parc Taulí n. 1, 08208, Sabadell, Spain

    Ana Roche Martínez

  18. Department of Radiology, Hospital Sant Joan de Déu, Pg Sant Joan De Deu Nº 2, 08950, Esplugues De Llobregat, Barcelona, Spain

    Jordi Muchart López

Authors
  1. Chiara Alfonsi
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  2. Christian Stephan-Otto
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  3. Elisenda Cortès-Saladelafont
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  4. Natalia Juliá Palacios
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  5. Inés Podzamczer-Valls
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  6. Nuria Gutiérrez Cruz
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  7. María Rosario Domingo Jiménez
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  8. Salvador Ibáñez Micó
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  9. Miguel Tomás Vila
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  10. Kathrin Jeltsch
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  11. Oya Kuseyri Hübschmann
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  12. Thomas Opladen
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  13. Ramón Velázquez Fragua
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  14. Teresa Gómez
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  15. Oscar Alcoverro Fortuny
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  16. Inmaculada García Jiménez
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  17. Eduardo López Laso
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  18. Ana Roche Martínez
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  19. Jordi Muchart López
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  20. Àngels Garcia-Cazorla
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Contributions

Chiara Alfonsi: conceptualization; data curation; resources; formal analysis; investigation; methodology; writing—original draft.

Christian Stephan-Otto: conceptualization; formal analysis; investigation; methodology; resources; software; validation; writing—original draft.

Elisenda Cortès-Saladelafont: conceptualization; data curation; writing—original draft.

Inés Podzamczer-Valls: data curation.

Natalia Juliá Palacios, Nuria Gutiérrez Cruz, María Rosario Domingo Jiménez, Salvador Ibáñez Micó, Miguel Tomás Vila, Ramón Velázquez Fragua, Teresa Gómez, Oscar Alcoverro Fortuny, Inmaculada García Jiménez, Eduardo López Laso, Ana Roche Martínez: data curation; resources; writing—review and editing.

Kathrin Jeltsch, Oya Kuseyri Hübschmann, Thomas Opladen: writing—review and editing.

Muchart Jordi López: data curation; software; resources; writing—review and editing.

Àngels Garcia-Cazorla: conceptualization; funding acquisition; investigation; project administration; resources; supervision; validation; visualisation; writing—review and editing.

Corresponding author

Correspondence to Àngels Garcia-Cazorla.

Ethics declarations

Ethics approval

The study was approved by the local ethics committee (ID number: PIC-131–18). All the procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2013.

Consent to participate

Oral and written informed consent was obtained from all subjects or their parents/legal guardians regarding publishing their data. Images from control subjects were obtained from a local anonymized MRI database, for which the patients or their parents/legal guardians gave informed consent.

Conflict of interest

Dr. Cortès-Saladelafont reports personal fees from Takeda, outside the submitted work. Dr. Kuseyri Hübschmann reports personal fees from PTC Therapeutics GT, outside the submitted work. Dr. López-Laso has received honoraria as an invited speaker and has also received consultation fees from PTC Therapeutics, outside the submitted work. Dr. Ibáñez-Micó reports grants and personal fees from PTC Therapeutics, during the conduct of the study. Dr. Alfonsi, Dr. Stephan-Otto, Dr. Juliá Palacios, Dr. Podzamczer-Valls, Dr. Nuria Gutiérrez, Dr. Kathrin Jeltsch, Dr. Velázquez Fragua, Dr. Alcoverro-Fortuny, Dr. Teresa Gómez, Dr. Roche Martínez and Dr. Muchart López have nothing to disclose.

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Alfonsi, C., Stephan-Otto, C., Cortès-Saladelafont, E. et al. Volumetric study of brain MRI in a cohort of patients with neurotransmitter disorders. Neuroradiology 64, 2179–2190 (2022). https://doi.org/10.1007/s00234-022-02989-8

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  • DOI: https://doi.org/10.1007/s00234-022-02989-8

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