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

BackgroundObesity 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.MethodsWe conducted a narrative review of the evidence in both humans and rodents, for the putative mechanisms underlying the link between obesity, migraine and IIH.ResultsTruncal 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.ConclusionsThis 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.     

The Relationship Between Idiopathic Intracranial Hypertension and Obesity

Objective.— Idiopathic intracranial hypertension (IIH) is usually considered to result from deficient intracranial absorption of cerebrospinal fluid, but has also been suggested to be caused by decreased cranial venous flow because of increased intrathoracic pressure resulting from intra‐abdominal obesity. To test this hypothesis, cerebrospinal fluid pressure (Pcsf), extracranial venous pressure (Pvf), intracranial venous pressure, and body mass index (BMI) were studied in patients with IIH with papilledema compared with patients with chronic tension‐type headache (CTTH). Design and Subjects.— The Pcsf and the pressures in frontal veins without (Pvf) and with bilateral compression of the supraorbital branch of the frontal veins and the superficial facial veins (Pvfc), the latter considered to be about equal to Pvfc, were studied in 10 consecutive patients with IIH with papilledema. Ten consecutive CTTH patients were used for controls. Orbital phlebography was performed to confirm that the compression of facial veins other than the frontal veins resulted in adequate communication between the frontal vein used for the studies and the cavernous sinus. Results.— Cerebrospinal fluid pressure was between 200 and 250 mm water in 5 of the CTTH patients and above 350 mm water in all IIH patients. Body mass index was >25 in all CTTH patients and similar in the 2 groups. Cerebrospinal fluid pressure was similar to Pvfc in all 10 CTTH patients but significantly greater in 6 of the 10 IIH patients. Pvf was similar in the 2 groups and related to BMI. Conclusions.— Chronic tension‐type headache patients may be prone to have Pcsf > 200 mm water and BMI > 25. Papilledema because of intracranial hypertension occurred in the present study at Pcsf > 350 mm water. The findings of Pvfc and Pcsf being similar in all CTTH patients support the suggestion that the techniques used for measuring intracranial venous pressure are adequate. The findings of similar BMI in the CTTH and the IIH patients who differed significantly as to Pcsf refute the hypothesis that obesity precedes, and is the cause of, intracranial hypertension in IIH. The difference between Pcsf and Pvfc in 6 of the IIH patients also does not support such a hypothesis but may indicate that IIH is due to deficient intracranial cerebrospinal fluid absorption. Since a relationship between intracranial hypertension and obesity is established and obesity is not found to cause intracranial hypertension in IIH, intracranial hypertension may be suggested to be the primary cause of weight increase in IIH. Obesity, however, may secondarily increase the preexistent IIH.     

BLIND OVERNIGHT: A case of fulminant idiopathic intracranial hypertension

Idiopathic Intracranial Hypertension (IIH) is a syndrome seen predominantly in obese women of reproductive age group, characterized by signs and symptoms of increased intracranial pressure due to an unknown cause. Some individuals have a more malignant form of disease called fulminant idiopathic intracranial hypertension with rapid worsening of symptoms over days. We report a case of 33 year-old obese female (BMI 36.9) who presented with a severe headache and blurred vision for one week, found to have idiopathic intracranial hypertension with rapid worsening of symptoms suggestive of a fulminant course of disease. She was managed with prompt surgical intervention. In patients with fulminant idiopathic intracranial hypertension, surgery such as cerebrospinal fluid shunting or optic nerve sheath fenestration should not be delayed to prevent vision loss.     

特发性颅内压增高的诊断与治疗现状

特发性颅内压增高呈自限性病程,大多数预后良好,但是少数可复发或慢性经过,慢性重度头痛和视功能障碍影响患者的工作和社会生活。永久性的视力障碍虽然少见,却是最严重的并发症,对特发性颅内压增高的明确诊断和有效治疗仍是困惑我们的难题。本文对特发性颅内压增高的诊断治疗及研究进展等进行综述如下。     

What is new about idiopathic intracranial hypertension? An updated review of mechanism and treatment

Idiopathic intracranial hypertension (IIH) is the syndrome of raised intracranial pressure without clinical, laboratory or radiological evidence of intracranial pathology. IIH is a relatively rare disease but rapidly increasing incidence is reported due to a global increasing incidence of obesity. Disease course is generally said to be self-limiting within a few months. However, some patients experience a disabling condition of chronic severe headache and visual disturbances for years that limit their capacity to work. Permanent visual defects are serious and not infrequent complications. The pathophysiology of IIH is still not fully understood. Advances in neuroimaging techniques have facilitated the exclusion of associated conditions that may mimic IIH. No causal treatment is yet known for IIH and existing treatment is symptomatic and rarely sufficient. The aim of this review is to provide an updated overview of this potentially disabling disease which may show a future escalating incidence due to obesity. Theories of pathogenesis, diagnostic criteria and treatment strategies are discussed.     

Emergency department presentation of idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, is a syndrome characterized by an elevated intracranial pressure in the absence of a focal lesion, infective process, or hydrocephalus. New onset IIH may present to the emergency department in a variety of ways. To describe the etiologic associations and clinical features in this disorder, we performed a retrospective analysis of consecutive emergency department patients with new onset IIH during the calendar years 1987-1996. A total of 52 patients met all study criteria. The mean patient age was 27+/-8.9 years; the female-to-male ratio was 7:1. An etiologic association could be identified in 85% of cases and included obesity, hypertension, drugs, endocrine, and systemic disorders. Headache was a dominant complaint in most patients (48/52) and associated with dizziness, nausea, and/or visual complaints. Fourteen patients (27%) were not diagnosed on their initial ED visit and were more likely to have atypical clinical features (71% vs. 24%; P = .004). Atypical features included paraesthesias, neck/back pain, unilateral headache, vertigo, and nystagmus. Papilledema, the ophthalmoscopic hallmark of IIH, was not detected initially in 11 patients (21%). These results suggest that IIH is a relatively uncommon neurological illness that may have a variety of causes. The emergency department diagnosis may be complicated by atypical clinical features and a lack of detectable papilledema.     

Treatment of idiopathic intracranial hypotension: cervicothoracic and lumbar blood patch and peroral steroid treatment

METHODS: Twelve consecutive patients with clinical symptoms and testing results compatible with a diagnosis of idiopathic intracranial hypotension (IIH), but no identifiable site of cerebrospinal fluid (CSF) leakage, were treated with a cervicothoracic or lumbar epidural "blood patch" (EBP) or orally administered steroids. RESULTS: Prompt and complete relief from headache persisting for at least 4 months was attained in 3 of 4 treatments with cervicothoracic EBP, 2 of 15 with lumbar EBP, and 4 of 8 with steroids. CONCLUSION: These results suggest that in patients who presumably suffer from IIH and yet have no identifiable site of CSF leakage, the presumed leakage more often occurs at the cervicothoracic level than the lumbar. In addition, our experience suggests that some IIH patients may be treated effectively with oral steroids and a trial of such therapy may be considered as an alternative to EBP.     

Idiopathic intracranial hypertension presenting with migraine phenotype is associated with unfavorable headache outcomes

Objective

To assess the prognostic impact of migraine headache in idiopathic intracranial hypertension (IIH).

Background

Migraine headache is common in IIH, but it is unclear whether it has prognostic relevance.

Methods

We investigated patients with IIH from the Vienna-IIH-database and differentiated migraine (IIH-MIG) from non-migraine headache (IIH-nonMIG) and without headache (IIH-noHA). Using multivariable models, we analyzed the impact of IIH-MIG on headache and visual outcomes 12 months after diagnosis.

Results

Among 97 patients (89% female, mean [SD] age 32.9 [11.1] years, median body mass index 32.0 kg/m², median cerebrospinal fluid opening pressure 310 mm), 46% were assigned to IIH-MIG, 37% to IIH-nonMIG (11% tension-type, 26% unclassifiable), and 17% to IIH-noHA. Overall, headache improvement was achieved in 77% and freedom of headache in 28%. The IIH-MIG group showed significantly lower rates for headache improvement (67% vs. 89% in IIH-nonMIG, p = 0.019) and freedom of headache (11% vs. 33% in IIH-nonMIG and 63% in IIH-noHA, p = 0.015). These differences persisted when only analyzing patients with resolved papilledema at follow-up. In contrast, visual worsening was significantly less common in IIH-MIG (9% vs. 28% in IIH-nonMIG and 31% in IIH-noHA, p = 0.045). In multivariable models, IIH-MIG was associated with a significantly lower likelihood of achieving headache improvement (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.40–0.78, p < 0.001) and freedom of headache (OR 0.29, 95% CI 0.12–0.46, p < 0.001), but also a lower risk for visual worsening (OR 0.26, 95% CI 0.04–0.82, p < 0.001).

Conclusions

In IIH, migraine headache is associated with unfavorable outcomes for headache, even when papilledema has resolved, and possibly favorable visual outcome.     

Intracranial hypertension and migraine

We describe the case report of a migraineur who developed daily postural headache due to benign intracranial hypertension. The CSF pressure was elevated despite the lack of papilledema on clinical examination. This case emphasizes that intracranial hypertension without papilledema must be in the differential diagnosis of the so-called "migraine transformation" headache. Accordingly, CSF analysis, including CSF pressure measurement, should be part of the diagnostic evaluation of "migraine transformation" headache.     

Cluster-like headache secondary to idiopathic intracranial hypertension

Few cluster-like headaches have been described. Idiopathic intracranial hypertension (IIH) presents with headaches in more than 90% of patients. We describe a male patient with new onset cluster-like headache secondary or related to IIH.     

The patients’ perspective on the burden of idiopathic intracranial hypertension

BackgroundIdiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure without evidence of a tumor or any other underlying cause. Headache and visual disturbances are frequent complaints of IIH patients, but little is known about other symptoms. In this study, we evaluated the patients’ perspective on the burden of IIH.MethodsFor this cross-sectional study, we developed an online survey for patients with IIH containing standardized evaluations of headache (HIT-6), sleep (PROMIS Sleep Disturbance Scale) and depression (MDI) in relation to BMI, lumbar puncture opening pressure (LP OP) and treatment.ResultsBetween December 2019 and February 2020, 306 patients completed the survey. 285 (93 %) were female, mean age was 36.6 years (± 10.8), mean BMI 34.2 (± 7.3) and mean LP OP at diagnosis was 37.8 cmH₂O (± 9.5). 219 (72 %) of the participants were obese (BMI ≥ 30); 251 (82 %) reported severe impacting headaches, 140 (46 %) were suffering from sleep disturbances and 169 (56 %) from depression. Higher MDI scores correlated with higher BMI and increased sleep disturbances. Patients with a normalized LP opening pressure reported less headaches, less sleep disturbances and less depression than those with a constantly elevated opening pressure.ConclusionsIn addition to headaches and visual disturbances, sleep disturbances and depression are frequent symptoms in IIH and contribute to the patients’ burden. Structured questionnaires can help to identify IIH patients’ needs and can lead to personalized and better treatment.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01283-x.     

Depression and anxiety in women with idiopathic intracranial hypertension compared to migraine: A matched controlled cohort study

Objective

To evaluate mental health burden in women with idiopathic intracranial hypertension (IIH) compared to matched women with migraine and population controls.

Background

Depression and anxiety are recognized comorbid conditions in those with IIH and lead to worse predicted medical outcomes. The mental health burden in IIH has not been previously evaluated in a large, matched cohort study.

Methods

We performed a population-based matched, retrospective cohort study to explore mental health outcomes (depression and anxiety). We used data from IQVIA Medical Research Data, an anonymized, nationally representative primary care electronic medical records database in the United Kingdom, from January 1, 1995, to September 25, 2019. Women aged ≥16 years were eligible for inclusion. Women with IIH (exposure) were matched by age and body mass index with up to 10 control women without IIH but with migraine (migraine controls), and without IIH or migraine (population controls).

Results

A total of 3411 women with IIH, 30,879 migraine controls and 33,495 population controls were included. Of these, 237, 2372 and 1695 women with IIH, migraine controls and population controls, respectively, developed depression during follow-up, and 179, 1826 and 1197, respectively, developed anxiety. There was a greater hazard of depression and anxiety in IIH compared to population controls (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.20–1.58; and aHR 1.40, 95% CI 1.19–1.64, respectively), while hazards were similar to migraine controls (aHR 0.98, 95% CI 0.86–1.13; and aHR 0.98, 95% CI 0.83–1.14, respectively).

Conclusion

Depression and anxiety burden in women with IIH is higher than in the general population, and comparable to that in matched women with migraine. This may indicate that presence of headache is a potential driver for comorbid depression and anxiety in IIH.     

Utility of Point-of-Care Ultrasound in the Diagnosis of Idiopathic Intracranial Hypertension in the Emergency Department

BackgroundEmergency physicians are frequently required to identify and triage patients with increased intracranial pressure (ICP). Idiopathic intracranial hypertension (IIH) is a possible cause that must be considered. Its prognosis depends on prompt recognition and treatment, and progression of the disease can lead to permanent vision loss and considerable morbidity. Point-of-care ultrasound can rapidly identify elevated ICP. Measurements of the optic nerve sheath diameter (ONSD) and optic disc elevation (ODE) can act as surrogates for ICP.Case SeriesWe describe five cases in which ultrasound was used to identify increased ICP and aid clinical decision-making. In several of the cases, ultrasound was used to confirm a suspicion for IIH and initiate therapy while awaiting the results of a more time-consuming and technically challenging test, such as lumbar puncture or optical coherence tomography. One of the patients was pregnant, and sonographic evidence of elevated ICP helped avoid exposing the patient to unnecessary radiation.Why Should an Emergency Physician Be Aware of This?Ultrasound is a quick and versatile tool for screening patients with neurologic symptoms, and when integrated into the proper clinical context, can reduce the use of more invasive tests. It can be particularly useful in patients with pathology that may not show abnormalities on computed tomography scan or in whom lumbar puncture is technically difficult, making patients at risk for IIH well-suited to examination by ultrasound. We use a cutoff of 5 mm for ONSD and 0.6 mm for ODE, though there are no universally agreed on cutoff values.     

Evaluation of acute headaches in adults

Classifying headaches as primary (migraine, tension-type or cluster) or secondary can facilitate evaluation and management A detailed headache history helps to distinguish among the primary headache disorders. "Red flags" for secondary disorders include sudden onset of headache, onset of headache after 50 years of age, increased frequency or severity of headache, new onset of headache with an underlying medical condition, headache with concomitant systemic illness, focal neurologic signs or symptoms, papilledema and headache subsequent to head trauma. A thorough neurologic examination should be performed, with abnormal findings warranting neuroimaging to rule out intracranial pathology. The preferred imaging modality to rule out hemorrhage is noncontrast computed tomographic (CT) scanning followed by lumbar puncture if the CT scan is normal. Magnetic resonance imaging (MRI) is more expensive than CT scanning and less widely available; however, MRI reveals more detail and is necessary for imaging the posterior fossa. Cerebrospinal fluid (CSF) analysis can help to confirm or rule out hemorrhage, infection, tumor and disorders related to CSF hypertension or hypotension. Referral is appropriate for patients with headaches that are difficult to diagnose, or that worsen or fail to respond to management     

Quantifying headache symptoms and other headache features from chart notes

OBJECTIVES: To describe a method for quantifying headache symptoms/features in family practice charts for patients diagnosed with headache NOS (not otherwise specified, ICD-9: 784) and to determine the share of NOS headache diagnoses with clinical data strongly suggestive of migraine or probable migraine headache. BACKGROUND: Headache is one of the most common pain symptoms that brings patients to a family physician. However, the majority of headache sufferers do not receive a specific headache diagnosis when they visit physicians. METHODS: We examined the chart notes of 454 patients exclusively diagnosed with one or more ICD-9 coded headache NOS diagnoses from July 1, 1995 through December 31, 1999 at a large suburban, university-affiliated practice. We developed a template containing 20 headache items combining International Headache Society diagnostic criteria and additional headache symptoms/features, and decision rules for coding symptoms/features and collected data from patient charts. We then developed decision rules and reclassified NOS headaches into categories strongly suggestive of migraine, probable migraine headache, or other diagnosis. Our main outcome measure is the consistency in the application of decision rules and diagnostic criteria. RESULTS: With this method we estimate 3 in 10 (29%) headache NOS patients may have had migraine (8%) or probable migraine headache (21%). Reclassified migraine visits averaged 6.5 migraine symptoms and reclassified probable migraine headache visits 4.7 migraine symptoms. Logistic regression analysis supports the consistency of diagnostic criteria for classifying headache based on coded symptoms/features--our model correctly predicted 96% of visits. Evidence of physical examination was recorded at 75% of visits suggesting that physician attention is focused on elimination of secondary headache. CONCLUSIONS: We think the use of our rigorous procedures reveals that a substantial amount of migraine and probable migraine headache may be missed in everyday practice. We hope our findings will provide a basis for the development of diagnostic methods more closely suited to the needs of nonspecialists, and contribute to a better standard of care for headache patients seen in primary care practice. Finally, we are hopeful that other researchers will consider using our template and guideline procedures in their efforts to identify diagnostic patterns and study headache and other health problems.     

Chronic Migraine: An Update on Physiology,Imaging, and the Mechanism of Action of Two Available Pharmacologic Therapies

Several lines of research support the hypothesis that migraine is a spectrum of illness, with clinical symptoms that vary along a continuum from episodic migraine to chronic migraine. Physiologic changes may result in episodic migraine evolving into chronic migraine over months to years in susceptible individuals. With chronification, headache frequency increases, becoming more disabling and less responsive to therapy. Neurophysiologic and functional imaging research has reported that chronic migraine may be associated with severity‐specific metabolic, functional, and structural abnormalities in the brainstem. Without longitudinal studies, it is unclear whether these changes may represent a continuum of individual progression and/or are reversible. Furthermore, chronic migraine is associated with larger impairments in cortical processing of sensory stimuli when compared with episodic migraine, possibly caused by more pronounced cortical hyperexcitability. Progressive changes in nociceptive thresholds and subsequent central sensitization due to recurrent migraine attacks in vulnerable individuals contribute to the chronic migraine state. This may result in changes to baseline neurologic function between headache attacks, evident in both electrophysiological and functional imaging research. Patients experiencing migraine chronification may report increased non‐headache pain, fatigue, psychiatric disorders (eg, depression, anxiety), gastrointestinal complaints, and other somatic conditions associated with their long‐term experience with migraine pain. Recent research provides a foundation for differentiating episodic and chronic migraine based on neurophysiologic and neuroimaging tools. In this literature review, we consider these findings in the context of models designed to explain the physiology and progression of episodic migraine into chronic migraine, and consider treatment of chronic migraine in susceptible individuals. Advances in pharmacotherapy provide treatment options for chronic migraine. Of the currently available treatment options, only onabotulinumtoxinA and topiramate have received regulatory approval and have demonstrated efficacy in patients with chronic migraine, although the exact mechanisms of action are not fully elucidated.     

The relation of brain ouabain-like compounds and idiopathic intracranial hypertension

OBJECTIVES: To determine the relationship between levels of ouabain-like compounds (OLC) in the cerebrospinal fluid (CSF) and the occurence of idiopathic intracranial hypertension (IIH). BACKGROUND: OLC are naturally occurring inhibitors of the sodium-potassium ATPase that are found in the CSF of mammals. Since the production of CSF is dependent upon sodium-potassium ATPase activity, and since there is evidence that the increased intracranial pressure found in the condition of IIH may be the result of increased CSF production, we hypothesized that the level of endogenous OLC would be reduced in the CSF of patients with IIH. METHODS: CSF samples were obtained from n = 7 patients with IIH and n = 31 patients with neurological disorders other than IIH ("control" patients) who had lumbar puncture as part of their routine evaluation or treatment. The concentration of OLC in the CSF samples was measured using an established ELISA. RESULTS: Patients with IIH exhibited a concentration of OLC in the CSF of 0.11 +/- 0.03 ng/mL. In comparison, the concentration of OLC in CSF samples from non-IIH control patients was 0.12 +/- 0.01 ng/mL. These values were not statistically different when compared with a t-test (P= 0.31). However, the concentration of OLC did negatively correlate to the opening pressure on lumbar puncture, but only in the IIH group (r=-0.80, P= .03). Furthermore, IIH patients who were newly diagnosed or who were unsuccessfully treated (n = 5 of 7 IIH patients) exhibited OLC concentrations of 0.06 +/- 0.1 ng/mL, which is nearly lower than that of the control group (P= .06). CONCLUSIONS: The average concentration of OLC in IIH patients (treated and untreated) is unlikely to be distinguishable from that in non-IIH control patients with other neurological conditions. However, the concentration of OLC may be inversely related to the intracranial pressure in patients with IIH, and it may prove to be lower in the subgroup of untreated and unsuccessfully treated IIH patients.     

Cluster-like headache and idiopathic intracranial hypertension: a case report

Cluster headache (CH) is a well-defined primary headache syndrome, but cases of symptomatic headache with clinical features of CH have been previously reported. Idiopathic Intracranial Hypertension (IIH) is a secondary headache disorder characterized by headache and visual symptoms, without clinical, radiological or laboratory evidence of intracranial pathology. Both papilloedema and IIH-related headache are typically bilateral, however asymmetrical or even unilateral localizations are described in literature. We report the case of a previously headache-free woman who presented cluster-like headache and asymmetrical papilloedema related to IIH. In our opinion the asymmetrical presentation supports, in this case, the hypothesis of cavernous sinus involvement in the IIH-related cluster-like headache pathogenesis.