Analysis of a cerebrospinal fluid protein called neurofilament light (NfL), which is linked to nerve cell damage, can help monitor the neurodegenerative process in patients with mitochondrial diseases.
This finding resulted from the study “Cerebrospinal fluid neurofilament light is associated with survival in mitochondrial disease patients,” which was published in the journal Mitochondrion.
Mitochondrial disease is a group of clinically and genetically variable illnesses that are caused by deregulation of the cell’s powerhouses, the mitochondria. They can manifest at any age and affect any organ or tissue, although the central nervous system and muscles are most typically affected because they are energy-demanding and highly dependent on mitochondria activity.
Due to the associated symptom variability and the complex nature of these disorders, a prompt and accurate diagnosis can be challenging, especially in pediatric patients.
Currently, clinicians have at their disposal several diagnostic tools and strategies, including neuroimaging, muscle and skin biopsy analyses, genetic assessments, and blood, urine, and cerebrospinal fluid (CSF) analysis. However, the results from these methods may not be totally conclusive, which can delay diagnosis and proper care.
Finding new biomarkers that can effectively help identify these diseases and monitor their progression are still needed. A team led by researchers at University of Gothenburg, in Sweden, evaluated if CSF biomarkers could help with this task.
They evaluated 52 patients with confirmed mitochondrial disease, 46 of whom had mitochondrial encephalopathy and six who had mitochondrial myopathy (muscle disease only) without central nervous system involvement, who were followed at the Queen Silvia Children’s Hospital. The study also enrolled 16 healthy volunteers as controls.
The researchers did not find any major differences between the levels of CSF biomarkers in mitochondrial myopathy patients and the control group. In contrast, the levels of CSF lactate and NfL levels were found to be 1.9 and 9.6 times higher in mitochondrial encephalopathy patients compared to controls.
When the researchers re-analyzed the CSF biomarkers according to the subtype of disorder, they found that CSF lactate was increased in all subtypes of mitochondrial disease assessed, except in MERRF (myoclonic epilepsy with ragged red fibers) and non-syndromic mitochondrial encephalopathy patients.
Patients with Leigh syndrome, MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes), and pyruvate dehydrogenase complex deficiency had significantly higher CSF NfL compared to controls. In addition, the researchers found that patients with Kearns-Sayre syndrome had reduced amounts of amyloid-β42 and higher P-tau than controls.
Next they evaluate if these differences in CSF biomarker’s levels could be associated disease outcome.
Analysis of brain magnetic resonance imaging (MRI) revealed that patients who had brain lesions due to nerve cell degeneration had higher levels of NfL. Any of the other biomarkers were associated to abnormal brain MRI results.
Indeed, high amounts of NfL in CSF were associated with 3.23 increased risk of death among mitochondrial encephalopathy patients.
Supported by these results the researchers believe that “CSF NfL may be used in the clinical setting as a biomarker of diagnostic and prognostic value in mitochondrial encephalopathy.” It also can “be used in clinical trials for selection and evaluation of novel therapies for mitochondrial diseases,” they suggested.