Metabolomics in Idiopathic Intracranial Hypertension to Identify Markers of Disease and Headache 2022

[pattismith]

DOI: https://doi.org/10.1212/WNL.0000000000201007

Nuclear Magnetic Resonance Spectroscopy Metabolomics in Idiopathic Intracranial Hypertension to Identify Markers of Disease and Headache

Background and Objective

We evaluated the metabolomic profile in the CSF, serum, and urine of participants with idiopathic intracranial hypertension (IIH) compared with that in controls and measured changes in metabolism associated with clinical markers of disease activity and treatment.

A case-control study compared women aged 18–55 years with active IIH (Friedman diagnostic criteria) with a sex-matched, age-matched, and body mass index–matched control group. IIH participants were identified from neurology and ophthalmology clinics from National Health Service hospitals and underwent a prospective intervention to induce disease remission through weight loss with reevaluation at 12 months.

RESULTS
Urea was lower in IIH participants (CSF; urine), correlated with ICP (urine) and headache severity (CSF), and increased by 12 months.

The lactate/pyruvate ratio was increased in IIH participants compared with that in controls (CSF) and decreased at 12 months (CSF).

acetate was higher in IIH participants (CSF, controls ), correlated with headache severity and headache disability, and was reduced at 12 months .

Ketones, 3-hydroxybutyrate and acetoacetate, were altered in the CSF at baseline in IIH participants and normalized at 12 months.

Discussion
We observed metabolic disturbances that are evident in the CSF, serum, and urine of IIH participants, suggesting global metabolic dysregulation.

Altered ketone body metabolites normaliser after therapeutic weight loss.

CSF/serum urea ratio was altered, which may influence ICP dynamics and headache.

Elevated CSF acetate, known to stimulate trigeminal sensitization, was associated with headache morbidity.

These alterations of metabolic pathways specific to IIH provide biological insight and warrant mechanistic evaluation.

 

[pattismith]

Elevated CSF acetate, known to stimulate trigeminal sensitization, was associated with headache morbidity.

trigeminal hyperexcitability has already been reported in IIH

Conclusions: The significant increase in R2 recovery rates in patients with IIH in remission suggests that there is an increased excitability in the trigeminal pathways

Trigeminal Hyperexcitability in Idiopathic Intracranial Hypertension: A Blink Reflex Study - PubMed (nih.gov)

 

[pattismith]

A new treatment for IIH with Exenatide

Conclusions

Exenatide reduced ICP acutely and after chronic dosing. GLP-1R agonists represent a new approach to treat IIH.

The Potentially Modifiable Risk Factor in Idiopathic Intracranial Hypertension | Neurology Clinical Practice