Dataset Information

Comorbidities in patients with Unverricht-Lundborg disease (EPM1).

ABSTRACT:

Background

Unverricht-Lundborg disease (EPM1) typically leads to accumulating disability. Disability may also be caused by comorbidities but there are no data available on these.

Aims of the study

To investigate the frequency of comorbidities in EPM1.

Methods

Comorbidity data of a previously described cohort of 135 Finnish patients with EPM1 were retrieved from neurological, surgical (including subspecialities), internal medicine (including subspecialities) and intensive care patient charts of the treating hospitals.

Results

Mean follow-up time was 31.4 years (SD 12.4 years, range 6.8-57.8 years), during which at least one comorbidity was observed in 107 patients (79%) and three or more in 53 (39%). The most common diagnostic categories were external injuries, mental and behavioural disorders and endocrine, nutritional and metabolic diseases. The most common single comorbid diagnosis was a fracture of the ankle (in 19% of all patients). The second most common single comorbid diagnosis in the cohort was diabetes (in 13% of all patients), and the third was depression, recorded for 13% of the cohort. Malignancies and cardiovascular end-organ damage were rare, whereas phimosis/paraphimosis appeared more common than in general population.

Conclusions

Patients with EPM1 often have comorbidities. Trauma and mental health risks should be especially followed and acted upon. Further studies are needed to more accurately comorbidity risks, characteristics and patient needs.

SUBMITTER: Sipila JOT

PROVIDER: S-EPMC9826374 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Comorbidities in patients with Unverricht-Lundborg disease (EPM1).

Sipilä Jussi O T JOT Kälviäinen Reetta R

Acta neurologica Scandinavica 20220913 5

<h4>Background</h4>Unverricht-Lundborg disease (EPM1) typically leads to accumulating disability. Disability may also be caused by comorbidities but there are no data available on these.<h4>Aims of the study</h4>To investigate the frequency of comorbidities in EPM1.<h4>Methods</h4>Comorbidity data of a previously described cohort of 135 Finnish patients with EPM1 were retrieved from neurological, surgical (including subspecialities), internal medicine (including subspecialities) and intensive ca ...[more]

PMID: 36097839

Similar Datasets

Project description:Unverricht-Lundborg disease (ULD), also known as progressive myoclonic epilepsy 1 (EPM1), is a rare autosomal recessive neurodegenerative disorder characterized by a complex symptomatology that includes action- and stimulus-sensitive myoclonus and tonic-clonic seizures. The main cause of the onset and development of ULD is a repeat expansion of a dodecamer sequence localized in the promoter region of the gene encoding cystatin B (CSTB), an inhibitor of lysosomal proteases. Although this is the predominant mutation found in most patients, the physio-pathological mechanisms underlying the disease complexity remain largely unknown. In this work, we used patient-specific iPSCs and their neuronal derivatives to gain insight into the molecular and genetic machinery responsible for the disease in two Italian siblings affected by different phenotypes of ULD. Specifically, fragment length analysis on amplified CSTB promoters found homozygous status for dodecamer expansion in both patients and showed that the number of dodecamer repeats is the same in both. Furthermore, the luciferase reporter assay showed that the CSTB promoter activity was similarly reduced in both lines compared to the control. This information allowed us to draw important conclusions: (1) the phenotypic differences of the patients do not seem to be strictly dependent on the genetic mutation around the CSTB gene, and (2) that some other molecular mechanisms, not yet clearly identified, might be taken into account. In line with the inhibitory role of cystatin B on cathepsins, molecular investigations performed on iPSCs-derived neurons showed an increased expression of lysosomal cathepsins (B, D, and L) and a reduced expression of CSTB protein. Intriguingly, the increase in cathepsin expression does not appear to be correlated with the residual amount of CSTB, suggesting that other mechanisms, in addition to the regulation of cathepsins, could be involved in the pathological complexity of the disease.

Dataset Information

Comorbidities in patients with Unverricht-Lundborg disease (EPM1).

Background

Aims of the study

Methods

Results

Conclusions

Publications

Comorbidities in patients with Unverricht-Lundborg disease (EPM1).

Similar Datasets

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