Pearls & Oy-sters: Cerebral Venous Congestion Associated With Cognitive Decline Treated by Jugular Release

Discussion

Descriptions of intracranial pressure (ICP) and its hypothesized relationship to arterial and venous blood flow were first published¹ in the late 18th century. He hypothesized that the sum of the volumes of brain, CSF, and intracranial blood is constant such that an increase in one must result in a decrease in another to maintain equilibrium. This principle has been used in understanding several neurologic disorders, specifically idiopathic intracranial hypertension (IIH), in which treatment is focused on CSF pressure and volume management.

Only recently has an association between cerebral vasculature hemodynamics and cerebral venous hypertension, sometimes referred to as congestion, been reported. Cerebral venous congestion (CVC) is a clinical state of symptoms secondary to relative reduction in venous outflow in the brain. CVC is most often interpreted in the context of IIH, venous hypertension, and venous stenosis. In 1995, King et al.² described venous stenosis through venography in IIH. Several case series characterized various rates of intracranial venous narrowing. Transverse sinus narrowing has been reported in as many as 93% of patients with IIH.³ Bilateral transverse flow abnormalities occur in up to 65% of patients and were not seen in age-matched controls.⁴ In 2002, Higgins et al.⁵ reported in Lancet a successful venous sinus stent placement in a woman with intractable IIH symptoms with bilateral transverse sinus stenosis. After dilation of a single transverse sinus, there were reduced pressure gradient and symptomatic relief. Further studies report that one-third of patients with IIH and isolated IJV stenosis who undergo venous stenting show resolution of symptoms including brain fog.⁶

Cognitive dysfunction is occasionally noted in patients with ICP abnormalities; however, the underlying pathophysiology is unknown. In a prospective case-control study of patients with IIH and controls who underwent neuropsychological testing, patients with IIH performed significantly worse in reaction time and processing speed. These impairments persisted on the three-month follow-up despite medical management.⁷ Traditional treatment options in IIH include weight loss and acetazolamide, although procedural diversion of CSF with shunts or optic nerve fenestration is typically reserved for medically refractory cases and venous stenting in transverse sinus stenosis.⁸ In rare cases, extrinsic compression resulting in venous stenosis has been described, particularly obstruction of the IJV from the C1 transverse process, cervical spondylosis, or styloid process.⁹ Surgical intervention to relieve obstruction through styloidectomy for the management of jugular stenosis in IIH has been explored and can provide symptomatic relief to patients.¹⁰

Moreover, intracranial dural arteriovenous fistulas (dAVFs) may infrequently manifest as progressive dementia, believed to be the result or contribution of venous hypertension in the cortex or bilateral thalami as part of a thalamic dementia syndrome.¹¹ In several case series, more than half of the patients undergoing dAVF obliteration experienced significant improvement in cognition or complete reversal of dementia-related symptoms at the six-month follow-up.¹¹

In the current case report, our patient suffered from venous congestion with TP elevated 10 mm Hg from the RA. To date, there are no established reference standards for TP because invasive venous manometry is not typically performed on control patients. Patients with suspected IIH with normal LP OP (<20 mm Hg) have measured TP ranges from 7 to 21 mm Hg.¹² The cited manuscript further describes a direct 1:1 relationship between venous sinus pressure (most accurately measured at the torcula) and OP (1 mm Hg increase per 1 cm H₂O increase, respectively).¹² We believe there is a connection between the venous system, CSF flow and pressure, and potentially blood-brain barrier (BBB), which most profoundly manifested clinically in our patient's cognitive decline.

Basic science research is underway to elucidate the pathogenic role of venous congestion in the brain resulting in cognitive decline. The current hypothesis within a mouse model of CVC showed distribution in the BBB and long-standing activation of neuroinflammatory-related gene expression as compared with control mice.¹³ After jugular vein ligation, the mice showed impaired spatial learning, gait, and cognitive function, as well as immunostaining of brain tissue with evidence of microglial activation. Further models have expanded to include venous dysfunction in human aging, specifically related to age-related cerebral white matter hyperintensities and cognitive decline.¹⁴ The designated venous hypothesis suggests pathologic changes in aging may be, in part, due to progressive degenerative changes in the intracranial venous system—increased venous wall stiffness, loss of compliance, increased pressure environment at the capillary bed, and further disruption of the blood-brain barrier.¹⁵ Understanding vascular changes that may contribute to such deficits in aging and open therapeutic targets to prevent cognitive decline is warranted.

Cognitive dysfunction is often multifactorial and can be seen across all age groups. This case illustrates a potential therapeutic target for cognitive decline. Further research is needed to elucidate the underlying pathophysiology of venous congestion and cognition. Recognizing the potential interrelationship between CVC, intracranial hypertension, CSF leaks, and cognitive impairment may accelerate diagnosis and treatment in such patients.