The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology

Figures & data

Figure 1 Overview of the interactions of ICP with all the nerves presented in this paper, the olfactory lymphatic pathway, and the inner ear.

Abbreviations: CSF, cerebrospinal fluid; ICP, intracranial pressure.

Table 1 Overview of the reported signs and symptoms for each condition that may be caused by increased ICP

Affected system	Signs and symptoms	IICH	FM	CFS
Hypothesis		Exacerbation of chronically increased CSP >20–25 cm H2O	Chronic moderate cerebrospinal hypertension (12–20 cm H2O) predominantly affecting the peripheral nervous system	Chronic moderate cerebrospinal hypertension (12–20 cm H2O) predominantly affecting the central nervous system
Increased cranial pressure	Migraine	70.4% of unresponsive migraine patients have IICH^Citation25	55.8%^Citation99	84%^Citation79
	Headaches	• 84% acute^Citation101 • 32% chronic^Citation104	68% tension headaches^Citation51	81% tension headaches^Citation79
	Fatigue	Common^Citation41	Core symptom^Citation20	Core symptom^Citation41
	Cognitive impairment	• Deficits in processing speed and reaction time^Citation105 • Persists after normalization of ICP^Citation103	Impaired processing speed^Citation56	Impaired processing speed^Citation22
	Loss of gray matter		3.3-fold greater age-associated decrease in gray matter volume^Citation57	Regional gray and white matter volume reduction^Citation76
Cranial nerve involvement	I Olfactory nerve	• Decreased olfactory bulb volume^Citation91 • Impaired olfactory function^Citation9	• Decreased olfactory bulb volume^Citation90 • Impaired olfactory function^Citation3
	II Optic nerve	• Increased optic nerve sheath diameter^Citation96 • Visual field constriction^Citation27 • Papilledema^Citation101	• Retinal nerve fiber thinning^Citation35 • Decreased perfusion of the optic nerve^Citation75 • 10% loss of peripheral vision^Citation102
	III Oculomotor IV Trochlear motor VI Abducens	• 18% double vision^Citation101 • Horizontal double vision^Citation59	• Eye motility dysfunction^Citation87 • 15% double vision^Citation102	Eye motility dysfunction^Citation6 Binocular vision dysfunction^Citation37
	V Trigeminal nerve Motor: muscles of mastication Sensory: face, cornea	Electromyography-proven trigeminal neuropathy^Citation4	• 71%–94% masticatory pain^Citation68 • Lacrimal nerve: ocular pain syndromes^Citation58 • Decreased corneal small fiber density^Citation77	21%–32% temporomandibular disorders^Citation83
	VII Facial nerve Motor: facial muscles	• 5% with seventh nerve palsy^Citation101
	VII Submandibular salivary glands and lacrimal glands	Sicca syndrome^Citation94	• > 49 years of age: 80% dry eye syndrome^Citation18 • 71% xerostomia^Citation81	82% Sicca syndrome^Citation89
	VIII Vestibulocochlear	Ménière’s disease^Citation21,Citation78,Citation95	• 30% vertigo^Citation102	Vestibular dysfunction^Citation5,Citation73
		Hearing loss^Citation21,Citation78,Citation101	25% hearing loss^Citation49,Citation102
	IX Glossopharyngeal X Vagus laryngeal and pharyngeal muscles		• 42% hoarseness^Citation102 • 37.3% dysphagia^Citation81
	X Vagus visceromotor	Slower gastric emptying associated with increased ICP^Citation66	• Belching, reflux, bloating, sour taste, and vomiting^Citation74	• Slower gastric emptying^Citation12
Olfactory lymphatic pathway	Evacuation of CSF via the lamina cribriformis to the lymphatic vessels of the nasal mucosa	• Sinusitis^Citation63 • Spontaneous CFS leak with rhinorrhea^Citation62	• 46% nonallergic rhinitis^Citation7	• Idiopathic nonallergic rhinitis is highly prevalent in CFS^Citation8

Notes: The percentages represent the proportion of patients displaying that sign or symptom, unless indicated otherwise.

Abbreviations: CFS, chronic fatigue syndrome; CSF, cerebrospinal fluid; CSP, cerebrospinal pressure; FM, fibromyalgia; ICP, intracranial pressure; IICH, idiopathic intracranial hypertension.

Table 2 Overview of the reported signs and symptoms for each condition that may be caused by increased spinal pressure

	Symptoms	IICH	FM	CFS
Increased spinal pressure	Allodynia/radiculopathy	Radiculopathy^Citation10,Citation38,Citation53,Citation67,Citation72,Citation88,Citation101	72% radiating pain^Citation55	Sharp, shooting, burning pain^Citation17
Cervical and lumbar nerve roots	Paresthesia/numbness in extremities	22% distal extremity paresthesia^Citation88	• 19%–84% numbness^Citation55,Citation102 • 88% stocking hypoesthesia^Citation16 • Objective sensory abnormalities^Citation98	69% numbness/paresthesia^Citation17,Citation24
	Weakness in the arms and legs	69% objective weakness^Citation53	• 58% objective weakness • 13% loss of muscle mass^Citation102	Muscle weakness and fasciculations^Citation17
	Electrodiagnostic abnormalities	62% signs of demyelinating polyneuropathy^Citation53	90% signs of demyelinating and/or axonal polyneuropathy^Citation15,Citation16,Citation97
	Walking difficulties/ataxia	12.2% ataxia^Citation33	• 26% abnormal tandem test due to ataxia • 63% poor balance^Citation102	Ataxia^Citation17 Reduced gait automaticity^Citation28
Sacral nerve roots	Constipation/irritable bowel/fecal incontinence		• 88% bloating • 56% constipation • 35% diarrhea • 56% incontinence^Citation2	38% irritable bowel^Citation45
	Bladder retention/irritable bladder/urinary incontinence	30% nocturia^Citation101	• Urodynamic testing: mostly detrusor overactivity^Citation23 • 39% irritable or painful bladder^Citation46	39.8% urinary incontinence or increased frequency^Citation45
Sympathetic overactivity	Sympathetic overactivity	Intracranial pressure is a determinant of sympathetic activity^Citation92	60% of studies describe sympathetic activity predominance^Citation62	60% of studies describe sympathetic activity predominance^Citation62
Miscellaneous	Female predominance	90% women^Citation11	1990 diagnostic criteria: 90% women^Citation20	90.9% women^Citation30
	Inheritance	5%–40% family members with IICH^Citation50,Citation101	Strong familial aggregation^Citation13	Significant relative risk among first-, second-, and third-degree relatives^Citation1
	Associated with EDS	Anecdotal reports of large case series suggest an association^Citation40	9% of EDS patients are diagnosed with FM^Citation85	Fatigue is common and often disabling in EDS^Citation39
	Obesity	88% obese^Citation101	34% of morbidly obese individuals have FM^Citation26	Increased prevalence of obesity^Citation70
	Depression/anxiety/quality of life	13% depression, 16% anxiety^Citation54	66% moderate-to-severe depression^Citation55	11% depression^Citation13
	Sleep disturbances	82%^Citation54	50%^Citation55	92%^Citation13
	Disability	31% of individuals change occupation due to IICH^Citation34	31% disability^Citation32	27%–41% unemployment rates^Citation65

Notes: The percentages represent the proportion of patients displaying that sign or symptom, unless indicated otherwise.

Abbreviations: CFS, chronic fatigue syndrome; CSP, cerebrospinal pressure; EDS, Ehlers-Danlos syndrome; FM, fibromyalgia; IICH, idiopathic intracranial hypertension.

Figure 2 Dilated optic nerve of a patient with visual field defects and unexplained widespread pain.

Figure 3 (A) Sacral nerve root sheath dilations can be observed, and these appear to be very similar to the optic nerve root sheath dilations. (B) A more lateral view of the sacrum showing significant dilation (Tarlov cyst) of nerve root S3.

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