A paradigm for chronic fatigue syndrome: caught between idiopathic intracranial hypertension and spontaneous intracranial hypotension; caused by cranial venous outflow obstruction, by J Nicholas P Higgins, John D Pickard in Fatigue: Biomedicine, Health & Behavior, 26 Jul 2021 [doi.org/10.1080/21641846.2021.1956223]

Article abstract:

Background

Clinical similarities between chronic fatigue syndrome and idiopathic intracranial hypertension, supported by measurements of intracranial pressure, invite suggestions that they may be connected, the first representing a mild version of the second. Yet, if this is to be the basis for a structural explanation for chronic fatigue syndrome, it already seems incomplete, failing to explain cases where disability seems disproportionate. Is there some other confounding variable?

Purpose

To refine, in this theoretical paper, an earlier model connecting chronic fatigue syndrome with idiopathic intracranial hypertension to allow for a cerebrospinal fluid (CSF) leak.

Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates [animals with backbones].          From: Wikipedia

Model

In this model, the primary structural problem is acquired obstruction to cranial venous outflow. This obstruction can take different forms, may be intermittent and subtle, and even be mistaken for normal venous anatomy, yet would be the driving force behind a tendency towards increased intracranial pressure. This chronic elevation of intracranial pressure stresses the dural membrane maintaining the integrity of the subarachnoid space, which can rupture at a weak point, allowing CSF to leak away and intracranial pressure to fall. The clinical manifestation of this disorder is the product of the severity of cranial venous outflow compromise and of the competing forces on intracranial pressure.

Figure 1. Obstruction to cranial venous outflow causes a rise in intracranial venous pressures leading to a rise in intracranial pressure and the syndrome of IIH. If a CSF leak develops before IIH becomes evident then the physiological disturbance manifests as spontaneous intracranial hypotension (SIH). IIH and SIH have multiple overlapping symptoms and patients may reach an equilibrium position between them, or may cycle between one and the other, reflecting opposing forces on intracranial pressure.

In some instances, a CSF leak will mitigate the effects of venous compromise, in others it will compound it, producing a disease spectrum ranging through idiopathic intracranial hypertension, chronic fatigue syndrome, fibromyalgia, and spontaneous intracranial hypotension.

Conclusion

In chronic fatigue syndrome a normal intracranial pressure does not exclude significant physiological disturbance.

Extract from full article:

We suggest, therefore, that cranial venous outflow obstruction can take different forms, may be intermittent and subtle, and even mistaken as part of normal variant anatomy, yet be the driving force behind a disorder of intracranial pressure in which pressure may be high, normal or low, depending on the nature and severity of venous compromise and whether or not it is complicated by a CSF leak.

We suggest that the clinical manifestation of this disorder will reflect, not just intracranial pressure, but also the underlying venous obstruction, and is represented by a spectrum which includes chronic fatigue syndrome, fibromyalgia, spontaneous intracranial hypotension and IIH. We suspect that a similar mechanism may be operative in other medically unexplained syndromes.