Elevated cerebrospinal fluid protein in <i><scp>POLG</scp></i>‐related epilepsy: Diagnostic and prognostic implications

Hikmat, Omar; Naess, K; Engvall, Martin; Klingenberg, Claus; Rasmussen, Magnhild; Tallaksen, Chantal; Brodtkorb, Eylert; Fiskerstrand, Torunn; Isohanni, Pirjo; Uusimaa, Johanna; Darín, Niklas; Rahman, Shamima; Bindoff, Laurence A.

doi:10.1111/epi.14459

Cited by 10 publications

(10 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…They postulated that these abnormalities were due to the accumulation of abnormal deleted mtDNA which may affect the integrity of the choroid plexus, thereby affecting the blood-brain barrier with loss of FRα, presumably via decreased exosome-shuttling, leading to low 5-MTFH levels and raised CSF protein [23]. Elevated CSF protein has been demonstrated in 70% of patients with POLG-related epilepsies and the level of CSF protein correlates with the severity of the clinical course [25].…”

Section: Significance and Mechanism Of Csf-folate Depletion And Discussion Of Treatmentmentioning

confidence: 99%

Alpers- and MNGIE-like disease with disturbed CSF folate transport and an unusual mode of genetic transmission of POLG mutations: a case report

Korinthenberg

Kirschner

Steinfeld

et al. 2021

JICNA

View full text Add to dashboard Cite

We report about a family with three of five siblings affected by a variable remitting-relapsing disease with epileptic seizures, coma and abdominal crises, and lethal outcome in all. In the youngest son and in one of his deceased brothers we identified two disease causing compound heterozygous POLG mutations. One of these was inherited from the mother, but the other was absent in the father`s blood, saliva, buccal swab and hair bulbs although his paternity was proven genetically. Thus, we assume germline mosaicism for this mutation in the father. Very low 5-methyltetrahydrofolate (5-MTHF) and absence of folate receptor-alpha was repeatedly found in the CSF of the youngest brother indicating a secondary cerebral folate transport deficiency. Folinic acid supplementation over 18 months resulted in some improvement of the neurological condition; however, it did not prevent progression of the systemic disease.

show abstract

Section: Significance and Mechanism Of Csf-folate Depletion And Discussion Of Treatmentmentioning

confidence: 99%

Alpers- and MNGIE-like disease with disturbed CSF folate transport and an unusual mode of genetic transmission of POLG mutations: a case report

Korinthenberg

Kirschner

Steinfeld

et al. 2021

JICNA

View full text Add to dashboard Cite

show abstract

“…To date, more than 190 disease-causing variants of the POLG gene have been identified, and about 100 of them have been linked to epilepsy. Epilepsy is a frequent comorbidity in POLG-related disorders, especially in childhood phenotypes, globally affecting 50–65% of individuals [ 64 , 65 ].…”

Section: Mitochondrial Epilepsy Phenotypesmentioning

confidence: 99%

“…Phenotypes developing during childhood are frequently the result of mtDNA depletion, and these include Alpers–Huttenlocher syndrome and myocerebrohepatopathy spectrum [ 65 ] ( Table 1 ). Alpers–Huttenlocher syndrome is hallmarked by refractory seizures, neurodevelopmental regression and liver dysfunction (developing later in the disease course) [ 66 ].…”

Section: Mitochondrial Epilepsy Phenotypesmentioning

confidence: 99%

Mitochondrial Epilepsy, a Challenge for Neurologists

Lopriore

Gomes

Montano

et al. 2022

IJMS

View full text Add to dashboard Cite

Primary mitochondrial diseases are relatively common inborn errors of energy metabolism, with a combined prevalence of 1 in 4300. These disorders typically affect tissues with high energy requirements, including the brain. Epilepsy affects >1% of the worldwide population, making it one of the most common neurological illnesses; it may be the presenting feature of a mitochondrial disease, but is often part of a multisystem clinical presentation. The major genetic causes of mitochondrial epilepsy are mutations in mitochondrial DNA and in the nuclear-encoded gene POLG. Treatment of mitochondrial epilepsy may be challenging, often representing a poor prognostic feature. This narrative review will cover the most recent advances in the field of mitochondrial epilepsy, from pathophysiology and genetic etiologies to phenotype and treatment options.

show abstract

“…There is a lack of validated biomarkers of disease progression in mitochondrial disease and management currently is supportive [83]. CSF lactate elevations simply relate to the neuropathological injury in SE [13] but CSF / serum albumin ratio as a biomarker may portend poorer outcome [84].…”

Section: Mitochondriamentioning

confidence: 99%

A tiered strategy for investigating status epilepticus

Craig

Mitchell

Thomas

2020

Seizure

View full text Add to dashboard Cite

In status epilepticus the imperative to start anti-seizure therapy, initially subjugates the need to investigate the cause. Once treatment is initiated this balance shifts in favour of identifying: the causes and consequences of the seizure; the factors that predetermined the occurrence of status epilepticus; and finally the prognosis of this acute episode. Just as there are multiple causes of seizures and epilepsy, there are a vast number of causes of status epilepticus. We discuss the more common and the more important to identify as they may dictate a change in therapy or a certain prognosis.Acknowledging that the burden of epilepsy and status epilepticus is preferentially felt in lower and middle income countries, we have tried to rationalise the investigation of status epilepticus. Basic laboratory studies are necessary in all patients with status epilepticus as systemic complications can occur early and can involve every organ system. Aetiology is important, however the morbidity from treatment does not discriminate when treatment resistant status epilepticus is due to dissociative seizures.Seven percent of epilepsy hospitalisations are for status epilepticus and epilepsy is a prior diagnosis half the time; awareness of prior history is invaluable. EEG is critical for diagnosis in the anaesthetised patient or those in non-convulsive status epilepticus. There is poor correlation of EEG with aetiology except in rare circumstances. Currently quantitative EEG methods should best be viewed as screening tool to reduce EEG reviewing time. MRI is clearly superior for identifying cytotoxic change and the networks that are or were involved in the episode of status epilepticus. Sequential imaging changes may give an estimate of recovery but there is insufficient detail to use MRI as a prognostication tool.We suggest the following model: 1) immediate investigations; 2) investigations targeted by the clinical scenario; 3) investigations targeted following results from bloods, imaging or EEG; 4) investigations targeted for rarer causes and super-refractory status epilepticus. First-line laboratory investigationsBasic laboratory studies are necessary in all SE patients as systemic complications can occur early and can involve every organ system. Laboratory data can aid early treatment strategies [6] and tools that

show abstract

Elevated cerebrospinal fluid protein in POLG‐related epilepsy: Diagnostic and prognostic implications

Cited by 10 publications

References 42 publications

Alpers- and MNGIE-like disease with disturbed CSF folate transport and an unusual mode of genetic transmission of POLG mutations: a case report

Alpers- and MNGIE-like disease with disturbed CSF folate transport and an unusual mode of genetic transmission of POLG mutations: a case report

Mitochondrial Epilepsy, a Challenge for Neurologists

A tiered strategy for investigating status epilepticus

Contact Info

Product

Resources

About