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Record W3121079554 · doi:10.1002/jimd.12360

Brain <scp>MR</scp> patterns in inherited disorders of monoamine neurotransmitters: An analysis of 70 patients

2021· article· en· W3121079554 on OpenAlexaff
Oya Kuseyri Hübschmann, Alexander Mohr, Jennifer Friedman, Filippo Manti, Gabriella Horváth, Elisenda Cortès‐Saladelafont, Saadet Mercimek‐Andrews, Yılmaz Yıldız, Roser Pons, Jan Kulhánek, Mari Oppebøen, Jeanette Koht, Inés Podzamczer‐Valls, Rosario Domingo‐Jiménez, Salvador Ibáñez, Òscar Alcoverro-Fortuny, Teresa Gómez‐Alemany, Pedro de Castro, Chiara Alfonsi, Dimitrios Zafeiriou, Eduardo López‐Laso, Philipp Guder, René Santer, Tomáš Honzík, Georg F. Hoffmann, Sven F. Garbade, Serap Sivri, Vincenzo Leuzzi, Kathrin Jeltsch, Ángeles García‐Cazorla, Thomas Opladen

Bibliographic record

VenueJournal of Inherited Metabolic Disease · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMetabolism and Genetic Disorders
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of TorontoBC Children's HospitalUniversity of British Columbia
FundersEuropean Regional Development FundInstituto de Salud Carlos IIIDietmar Hopp StiftungPTC TherapeuticsMinisterstvo Zdravotnictví Ceské RepublikyBiogen
KeywordsMedicineTetrahydrobiopterinMonoamine neurotransmitterEncephalopathyInternal medicineNeuroimagingCerebral atrophyPathologyEndocrinologyAtrophySerotoninPsychiatryNitric oxideNitric oxide synthase

Abstract

fetched live from OpenAlex

Inherited monoamine neurotransmitter disorders (iMNDs) are rare disorders with clinical manifestations ranging from mild infantile hypotonia, movement disorders to early infantile severe encephalopathy. Neuroimaging has been reported as non-specific. We systematically analyzed brain MRIs in order to characterize and better understand neuroimaging changes and to re-evaluate the diagnostic role of brain MRI in iMNDs. 81 MRIs of 70 patients (0.1-52.9 years, 39 patients with tetrahydrobiopterin deficiencies, 31 with primary disorders of monoamine metabolism) were retrospectively analyzed and clinical records reviewed. 33/70 patients had MRI changes, most commonly atrophy (n = 24). Eight patients, six with dihydropteridine reductase deficiency (DHPR), had a common pattern of bilateral parieto-occipital and to a lesser extent frontal and/or cerebellar changes in arterial watershed zones. Two patients imaged after acute severe encephalopathy had signs of profound hypoxic-ischemic injury and a combination of deep gray matter and watershed injury (aromatic l-amino acid decarboxylase (AADCD), tyrosine hydroxylase deficiency (THD)). Four patients had myelination delay (AADCD; THD); two had changes characteristic of post-infantile onset neuronal disease (AADCD, monoamine oxidase A deficiency), and nine T2-hyperintensity of central tegmental tracts. iMNDs are associated with MRI patterns consistent with chronic effects of a neuronal disorder and signs of repetitive injury to cerebral and cerebellar watershed areas, in particular in DHPRD. These will be helpful in the (neuroradiological) differential diagnosis of children with unknown disorders and monitoring of iMNDs. We hypothesize that deficiency of catecholamines and/or tetrahydrobiopterin increase the incidence of and the CNS susceptibility to vascular dysfunction.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.133
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.007
GPT teacher head0.246
Teacher spread0.239 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations17
Published2021
Admission routes1
Has abstractyes

Explore more

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