Understanding the link between obesity and headache- with focus on migraine and idiopathic intracranial hypertension

Abstract Background Obesity confers adverse effects to every system in the body including the central nervous system. Obesity is associated with both migraine and idiopathic intracranial hypertension (IIH). The mechanisms underlying the association between obesity and these headache diseases remain unclear. Methods We conducted a narrative review of the evidence in both humans and rodents, for the putative mechanisms underlying the link between obesity, migraine and IIH. Results Truncal adiposity, a key feature of obesity, is associated with increased migraine morbidity and disability through increased headache severity, frequency and more severe cutaneous allodynia. Obesity may also increase intracranial pressure and could contribute to headache morbidity in migraine and be causative in IIH headache. Weight loss can improve both migraine and IIH headache. Preclinical research highlights that obesity increases the sensitivity of the trigeminovascular system to noxious stimuli including inflammatory stimuli, but the underlying molecular mechanisms remain unelucidated. Conclusions This review highlights that at the epidemiological and clinical level, obesity increases morbidity in migraine and IIH headache, where weight loss can improve headache morbidity. However, further research is required to understand the molecular underpinnings of obesity related headache in order to generate novel treatments.

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Preclinical update on regulation of intracranial pressure in relation to idiopathic intracranial hypertension

Fluids and Barriers of the CNS ◽

10.1186/s12987-019-0155-4 ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 4

Author(s):

Sajedeh Eftekhari ◽

Connar Stanley James Westgate ◽

Maria Schmidt Uldall ◽

Rigmor Hoejland Jensen

Keyword(s):

Intracranial Pressure ◽

Intracranial Hypertension ◽

Idiopathic Intracranial Hypertension ◽

Drug Targets ◽

Molecular Mechanisms ◽

Special Focus ◽

Icp Monitoring ◽

Preclinical Research ◽

New Drug

Abstract Background Elevated intracranial pressure (ICP) is observed in association with a range of brain disorders. One of these challenging disorders is idiopathic intracranial hypertension (IIH), characterized by raised ICP of unknown cause with significant morbidity and limited therapeutic options. In this review, special focus is put on the preclinical research performed in order to understand the pathophysiology behind ICP regulation and IIH. This includes cerebrospinal fluid dynamics, molecular mechanisms underlying disturbances in brain fluids leading to elevated ICP, role of obesity in IIH, development of an IIH model and ICP measurements in rodents. The review also discusses existing and new drug targets for IIH that have been evaluated in vivo. Conclusions ICP monitoring in rodents is challenging and different methods have been applied. Some of these methods are invasive, depend on use of anesthesia and only allow short-term monitoring. Long-term ICP recordings are needed to study IIH but existing methods are hampered by several limitations. As obesity is one of the most common risk factors for IIH, a rodent obese model has been developed that mimics some key aspects of IIH. The most commonly used drugs for IIH have been evaluated in vivo for their efficacy at lowering ICP in the existing animal models. These studies suggest these drugs, including acetazolamide, might have limited or no reducing effect on ICP. Two drug targets that can impact ICP in healthy rodents are topiramate and a glucagon-like peptide-1 receptor (GLP-1R) agonist. However, it remains to evaluate their effect in an IIH model with more precise and valid ICP monitoring system. Therefore, continued evaluation in the preclinical research with refined tools is of great importance to further understand the pathophysiology behind disorders with raised ICP and to explore new drug targets.

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1338 Bariatric Surgery as a Viable Treatment for Idiopathic Intracranial Hypertension: A Case Series

British Journal of Surgery ◽

10.1093/bjs/znab259.195 ◽

2021 ◽

Vol 108 (Supplement_6) ◽

Author(s):

V Mahendran ◽

P Ricart ◽

M Wadley ◽

A Perry ◽

S Robinson

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Intracranial Hypertension ◽

Idiopathic Intracranial Hypertension ◽

Case Series ◽

Radicular Pain ◽

Csf Pressure ◽

Disease Modifying Therapy ◽

Effective Treatment Modality ◽

Preventable Blindness

Abstract Introduction Idiopathic Intracranial Hypertension (IIH) is a significant cause of preventable blindness. Patients also suffer from debilitating headaches, pulsatile tinnitus, nausea, vomiting, photophobia, and radicular pain. If IIH continues to rise as predicted, treatment cost will increase to 462.7 million GBP annually by 2030. Weight loss is the only proven disease-modifying therapy for reversal of IIH. Bariatric surgery is an attractive treatment option due to superlative weight loss and reversal of related comorbidities. The case series aims to raise awareness of bariatric surgery as a safe and effective treatment modality for IIH. Method The case series consists of a retrospective analysis of four patients with a pre-operative diagnosis of IIH. They were referred to our department for bariatric surgery between January to December 2018. They were followed up for a total of two years. Results In our case series, all four patients were females with a mean age of 34 years. Mean BMI reduced from 47.3 kg/m2 before surgery to 30 kg/m2 with an EWL of 76.4% at the end of two years after surgery. They all showed significant improvement or resolution in their symptoms related to IIH, and none of them required further CSF pressure reducing procedures afterwards. Conclusions Bariatric surgery is a safe and effective method of treating IIH. It is superior compared to medical management and CSF pressure reducing procedures which have high rates of recurrence.

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The Potentially Modifiable Risk Factor in Idiopathic Intracranial Hypertension: Body Weight

Neurology Clinical Practice ◽

10.1212/cpj.0000000000001063 ◽

2021 ◽

pp. 10.1212/CPJ.0000000000001063

Author(s):

Susan P Mollan ◽

Abd A Tahrani ◽

Alexandra J Sinclair

Keyword(s):

Weight Loss ◽

Body Weight ◽

Risk Factor ◽

Intracranial Pressure ◽

Intracranial Hypertension ◽

Treatment Strategy ◽

Idiopathic Intracranial Hypertension ◽

Potential Treatment ◽

Distal Small Intestine

AbstractPurpose of review:Idiopathic intracranial hypertension (IIH) prevalence increased in conjunction with rising obesity rates. Here, we highlight the importance of weigh management in IIH, and introduce glucagon-like peptide 1 (GLP-1) receptor agonists (RA) as potential treatment strategy for IIH.Recent findings:Weight gain is a risk factor for IIH; and weight loss (via any treatment strategy) plays a key role in IIH management. GLP-1 is an incretin secreted by the distal small intestine in response to a meal. GLP-1 RA have been shown to improve glycaemic control (no. hypoglycaemia) and lower body weight in patients with and without type 2 diabetes. The choroid plexus has been found to express GLP-1 receptors and treatment with a GLP-1 RA significantly reduces cerebrospinal fluid secretion in vitro and intracranial pressure in rodents.Summary:New research evaluating the pathophysiology of IIH supports GLP-1 RA as a potential treatment for IIH via weight loss dependant and independent mechanism to directly reduce intracranial pressure.

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Obesity and Weight Loss in Idiopathic Intracranial Hypertension

Journal of Neuro-Ophthalmology ◽

10.1097/wno.0000000000000448 ◽

2017 ◽

Vol 37 (2) ◽

pp. 197-205 ◽

Cited By ~ 24

Author(s):

Suresh Subramaniam ◽

William A. Fletcher

Keyword(s):

Weight Loss ◽

Intracranial Hypertension ◽

Idiopathic Intracranial Hypertension

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Therapeutic lumbar puncture for headache in idiopathic intracranial hypertension: Minimal gain, is it worth the pain?

Cephalalgia ◽

10.1177/0333102418782192 ◽

2018 ◽

Vol 39 (2) ◽

pp. 245-253 ◽

Cited By ~ 14

Author(s):

Andreas Yiangou ◽

James Mitchell ◽

Keira Annie Markey ◽

William Scotton ◽

Peter Nightingale ◽

...

Keyword(s):

Intracranial Hypertension ◽

Lumbar Puncture ◽

Idiopathic Intracranial Hypertension ◽

Rating Scale ◽

Acute Effect ◽

Numeric Rating Scale ◽

Severe Exacerbation ◽

Opening Pressure ◽

Headache Severity ◽

Numeric Rating

Background Headache is disabling and prevalent in idiopathic intracranial hypertension. Therapeutic lumbar punctures may be considered to manage headache. This study evaluated the acute effect of lumbar punctures on headache severity. Additionally, the effect of lumbar puncture pressure on post-lumbar puncture headache was evaluated. Methods Active idiopathic intracranial hypertension patients were prospectively recruited to a cohort study, lumbar puncture pressure and papilloedema grade were noted. Headache severity was recorded using a numeric rating scale (NRS) 0–10, pre-lumbar puncture and following lumbar puncture at 1, 4 and 6 hours and daily for 7 days. Results Fifty two patients were recruited (mean lumbar puncture opening pressure 32 (28–37 cmCSF). At any point in the week post-lumbar puncture, headache severity improved in 71% (but a small reduction of −1.1 ± 2.6 numeric rating scale) and exacerbated in 64%, with 30% experiencing a severe exacerbation ≥ 4 numeric rating scale. Therapeutic lumbar punctures are typically considered in idiopathic intracranial hypertension patients with severe headaches (numeric rating scale ≥ 7). In this cohort, the likelihood of improvement was 92% (a modest reduction of headache pain by −3.0 ± 2.8 numeric rating scale, p = 0.012, day 7), while 33% deteriorated. Idiopathic intracranial hypertension patients with mild (numeric rating scale 1–3) or no headache (on the day of lumbar puncture, prior to lumbar puncture) had a high risk of post- lumbar puncture headache exacerbation (81% and 67% respectively). Importantly, there was no relationship between lumbar puncture opening pressure and headache response after lumbar puncture. Conclusion Following lumbar puncture, the majority of idiopathic intracranial hypertension patients experience some improvement, but the benefit is small and post-lumbar puncture headache exacerbation is common, and in some prolonged and severe. Lumbar puncture pressure does not influence the post-lumbar puncture headache.

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