Evidence map›Paper›PMID 33966627›Full record

ArticleNeurological research and practice2021

Treatment of progressive multiple sclerosis with high-dose all-trans retinoic acid - no clear evidence of positive disease modifying effects.

Christoph Ruschil, Evelyn Dubois, Maria-Ioanna Stefanou, Markus Christian Kowarik, Ulf Ziemann, Marcus Schittenhelm, Markus Krumbholz, Felix Bischof

Open access · diamondAbstract read
In one paragraph

Article in Neurological research and practice, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 25% of its field
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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026
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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

8 authors at 3 institutions in 2 countries.

Christoph RuschilDepartment of Neurology & Stroke, Eberhard-Karls University, Tübingen, Germany. Christoph.ruschil@uni-tuebingen.de.ORCID http://orcid.org/0000-0001-9900-4295
Evelyn DuboisDepartment of Neurology & Stroke, Eberhard-Karls University, Tübingen, Germany.
Maria-Ioanna StefanouDepartment of Neurology & Stroke, Eberhard-Karls University, Tübingen, Germany.
Markus Christian KowarikDepartment of Neurology & Stroke, Eberhard-Karls University, Tübingen, Germany.
Ulf ZiemannDepartment of Neurology & Stroke, Eberhard-Karls University, Tübingen, Germany.
Marcus SchittenhelmDepartment of Hematology, Oncology, Clinical Immunology and Rheumatology, Eberhard-Karls University, Tübingen, Germany.
Markus KrumbholzDepartment of Neurology & Stroke, Eberhard-Karls University, Tübingen, Germany.
Felix BischofHertie Institute for Clinical Brain Research, Eberhard-Karls University, Tübingen, Germany.
Hertie Institute for Clinical Brain Research · DEKantonsspital St. Gallen · CHKonrad-Adenauer-Stiftung · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAll-trans retinoic acid (ATRA) is an acid derivative of vitamin A which is discussed as a promising candidate to ameliorate the disease course of multiple sclerosis (MS) by immunomodulation or even by promoting regeneration in progressive MS. Here we report a patient who significantly improved for MS related disability following administration of chemotherapy including ATRA for mitoxantrone-related acute promyelocytic leukemia and assess the effect of high-dose ATRA in three additional patients with progressive MS.

methodsPatients with progressive MS who had failed previous therapies were treated with high-dose ATRA. Patients underwent clinical and routine laboratory monitoring. Additionally, PBMCs were analyzed by flow cytometry for lymphocyte subsets.

resultsATRA was well tolerated and no pathological laboratory abnormalities were observed. After initial mild (not statistically significant) improvement of EDSS and mean MSFC z-score, ongoing disease progression was observed. One patient subacutely experienced severe cognitive and motor worsening. Cerebral MRI revealed persistent gadolinium-enhancing lesions. Flow cytometric alterations of peripheral blood naïve, central memory and effector memory CD4 and CD8 T cells, B lymphocytes, plasma cells, memory B cells, plasmablasts and natural killer (NK) cells did not reach statistical significance.

conclusionsStand-alone therapy with ATRA did not ameliorate progressive MS in our limited cohort and we did not observe consistent alterations of T and B cell subsets. Intriguingly, application of ATRA may have caused marked disease exacerbation in one patient.

Indexed as

All-trans retinoic acidLymphocyte subsetsProgressive multiple sclerosisVitamin A

Identifiers

PMID33966627
PMCPMC8108354
OpenAlexW3160873844

What OpenQuestion 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 OpenQuestion graph.