Evidence map›Paper›PMID 41180951›Full record

ArticleBrain communications2025

Deep clinical, genetic, and serum biomarker profiling indicates glial and neuronal pathology in primary brain calcification.

Janine Schwahn, Sophie Hebestreit, Olivia Kosche, Petra Steinacker, Vesile Sandikci, Isabel Winzer, Jasper Hesebeck-Brinckmann, Franziska Bachhuber, Ivan Valkadinov, Stefanie Nittka and 23 more

Abstract read
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In one paragraph

Article in Brain communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

33 authors.

Janine SchwahnDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Sophie HebestreitDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Olivia KoscheDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Petra SteinackerDepartment of Neurology, Martin-Luther-University of Halle-Wittenberg, Halle (Saale) 06120, Germany.
Vesile SandikciDepartment of Neurology, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Isabel WinzerDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Jasper Hesebeck-BrinckmannDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Franziska BachhuberDepartment of Neurology, University of Ulm, Ulm 89081, Germany.
Ivan ValkadinovDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Stefanie NittkaInstitute for Clinical Chemistry, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Lukas MesinDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Max BraunerDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Christine von ArnimDepartment of Geriatrics, University of Göttingen Medical Center, Göttingen 37075, Germany.
Nandhini SanthanamDepartment of Biomedical Informatics, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Marvin SpreyerDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Robert SackmaierDepartment of Neurology, Elisabethinen Clinic, Graz 8020, Austria.
Antje KnehrDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Paula BarthelDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Oliver BährDepartment of Neurology, Aschaffenburg-Alzenau Clinic, Aschaffenburg 63739, Germany.
Herbert GruberDepartment of Neurology, Aschaffenburg-Alzenau Clinic, Aschaffenburg 63739, Germany.
Sabine StallforthDepartment of Molecular Neurology, University Hospital Erlangen, Erlangen 91054, Germany.
Martin RegensburgerDepartment of Molecular Neurology, University Hospital Erlangen, Erlangen 91054, Germany.ORCID https://orcid.org/0000-0002-2172-7386
Jürgen WinklerDepartment of Molecular Neurology, University Hospital Erlangen, Erlangen 91054, Germany.
Rüstem YilmazDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Michael NeumaierInstitute for Clinical Chemistry, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Hayrettin TumaniDepartment of Neurology, University of Ulm, Ulm 89081, Germany.
Mate E MarosDepartment of Biomedical Informatics, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Holger WenzDepartment of Neuroradiology, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
David BrennerDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.ORCID https://orcid.org/0000-0002-1535-3146
Markus OttoDepartment of Neurology, Martin-Luther-University of Halle-Wittenberg, Halle (Saale) 06120, Germany.
Anne EbertDepartment of Neurology, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
Julian ConradDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.ORCID https://orcid.org/0000-0001-7912-0571
Jochen H WeishauptDivision of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Primary brain calcification (primary familial brain calcification in inherited cases) is an often-genetic condition characterized by symmetrical brain calcifications and neuropsychiatric symptoms. The calcifications can also occur without overt clinical symptoms. Identifying laboratory biomarkers in primary brain calcification and their association with imaging, genetic, and clinical data will be crucial for a deeper understanding of primary brain calcification causation and progression and the planning of therapeutic trials. The serum biomarkers for neuronal degeneration (phosphorylated tau, neuron-specific enolase, neurofilament light- and heavy chain) and glial activation (glial fibrillary acidic protein, S100 calcium-binding protein B) were measured in 101 probands (41 controls and 60 probands with primary brain calcification). The deep phenotyping protocol of the German Fahr-NET register included neurological and neuropsychological examination, routine laboratory workup, and whole exome sequencing. We also performed and analyzed 45 cranial CT scans using the total calcification score. While mild pallidal calcifications were observed early in young, asymptomatic primary brain calcification mutation carriers, individuals with calcifications extending beyond the pallidum were symptomatic. Individuals with primary brain calcification had elevated serum glial fibrillary acidic protein and neurofilament light chain levels. Serum biomarkers correlated with both the extent of calcifications and the clinical impairment. Elevated parathyroid hormone levels distinguished the primary brain calcification group without identified mutation from both genetic primary brain calcification and control groups. Our results define a practical imaging cut-off indicating the presence of primary brain calcification symptoms. Elevated parathyroid hormone levels in primary brain calcification without identified mutation, but not in primary brain calcification with a monogenic cause, suggest abortive calcium regulation defects as a pathogenic factor specifically for primary brain calcification without identified mutation. Elevated glial fibrillary acidic protein and neurofilament concentrations in individuals with primary brain calcification indicate early, chronic astrocytosis and neuronal impairment, respectively. The significant association of neurofilament light chain with clinical scores and brain imaging results will be relevant for future therapeutic studies.

Indexed as

basal ganglia calcificationbiomarkermovement disorderneurogeneticsprimary brain calcification

Identifiers

PMID41180951
PMCPMC12574706

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.