Reversible Encephalopathy Due to Venous Hypertension From Arteriovenous Hemodialysis Graft

Abstract

Venous congestive encephalopathy is a rare complication in patients with arteriovenous hemodialysis grafts. It commonly manifests as encephalopathy of fluctuating severity, often with seizures. Because these patients typically have multiple significant chronic health problems, venous hypertension’s contribution to the patient’s cognitive decline can easily be overlooked. This nonspecific presentation can make diagnosis challenging, therefore delaying treatment. We describe a case of progressive, fluctuating encephalopathy with seizures due to cerebral venous congestion caused by arterial shunting from an upper limb arteriovenous (AV) fistula to the proximal venous system, that was initially unrecognized, yet ultimately reversed by elimination of the source of venous hypertension.

Case Report

A 71 year-old woman with end stage renal disease (ESRD) on hemodialysis (HD), was admitted multiple times over several months for fluctuating encephalopathy with new-onset epilepsy.

Arteriovenous (AV) access for HD was first established in 2012 in the form of a right upper extremity AV fistula. Over the next 5 years this required several revisions with presence of severe stenosis of the right brachiocephalic vein. Ultimately, a right brachial to jugular AV graft was created in March 2017, 6 months before onset of encephalopathy (Figure 1).

Figure 1.

March 2017 CT neck. Coronal view. Thick arrow = brachial artery to IJ shunt graft; thin arrow = old, thrombosed brachial artery to subclavian vein shunt graft; dotted arrow = dilated IJ vein at level of shunt anastomosis.

In September of 2017 the patient presented with cognitive decline that developed over days and was associated with fever (39.0 ^oC). She was alert and oriented to time and place, but very inattentive, diffuse myoclonus and action tremor in the upper extremities bilaterally were present. Her visual acuity was severely impaired but unchanged compared to prior (finger count only OU), and fundoscopic examination was not performed due to the presence of severe cataract on OD and prior vitreous hemorrhages on OS. Laboratory analysis showed leukocytosis (24.53 K/μL), normal lactic acid levels, mild elevated BUN (27 mg/dl) and creatinine (6.5 mg/dl) that were similar to prior evaluation. Urinalysis show bacteria and pyuria, with cultures showing mixed urogenital flora. EEG showed moderate diffuse background slowing with no epileptiform activity. She was diagnosed with a urinary tract infection (UTI) and secondary encephalopathy, but despite antibiotic treatment with vancomycin and cefepime for 7 days and normalization of leukocytosis, the encephalopathy persisted with fluctuation in severity during the hospital course. MRI brain showed a left frontal subdural hematoma, believed to be due to a fall 3 weeks prior admission. Computerized tomography angiogram (CTA) of the head (Figure 2A-C) showed prominence of the left occipitotemporal cortical veins without evidence of a dural arteriovenous fistula or arteriovenous malformation and, previously demonstrated congenitally small L transverse/sigmoid sinus, and new prominence of the right transverse and sigmoid venous sinuses. MRI brain did not show any additional abnormalities. These findings were attributed to reverse flow from the upper limb AV graft, and thought to be unrelated to the patient’s presentation. Her hospital course was complicated by a generalized tonic-clonic seizure, which did not recur after treatment with levetiracetam.

Figure 2.

Sept 2017 CT head. A) Axial MIP reconstruction showing right transverse sinus dilation (bold arrow) and small left transverse sinus (dotted arrow), B and C) Axial MIP reconstruction showing left cerebral venous congestion (bold arrow). May 2018 CT head. D) Axial MIP reconstruction showing worsening right transverse sinus dilation (bold line) and small left transverse sinus (dotted line), E and F) Axial MIP reconstruction showing worsening left cerebral venous congestion. R: right, L: left (bold arrow).

Despite partial clinical recovery upon discharge, including resolution of action tremor and myoclonus and improved attention, she continued to have significant fluctuations of cognitive functions that in the following months required hospitalization. At her best, she was oriented to person, place, month and year, was able to follow simple commands, and adventitious movements were absent. At worst she could only open her eyes to verbal stimulation, but not track or follow simple commands, and had prominent myoclonus and asterixis. She was hospitalized 6 times over the course of 9 months for the following reasons: bacterial pneumonia and hypertensive emergency, recurrent seizure, acute encephalopathy with hyponatremia and hypothermia, C.Diff colitis (twice) and hypertensive encephalopathy. Neurology was consulted during most but not all of the admissions. Due to the presence of concomitant metabolic or infectious disorder during each admission, the etiology of the encephalopathy was thought to be toxic-metabolic. Despite adequate treatment of these, the encephalopathy only transiently improved and psychomotor slowing, inconsistent orientation, and intermittent myoclonus persisted. Prior Sept 2017 patient was living independent at home, although due to the progressive functional and cognitive decline she was transferred to nursing home in Jan 2018.

In May 2018 she again presented with worsening encephalopathy. Neurologic examination was notable for decreased level of arousal, characterized by drowsiness, ability to open eyes to verbal and tactile stimuli, incomprehensible speech, inability to follow commands, and moderate bilateral myoclonus. Laboratory analysis was overall unremarkable with no leukocytosis and no electrolytes abnormalities with the exception of known renal insufficiency. EEG showed diffuse background slowing (mixed delta and theta frequencies) with no epileptiform activity seen in association with myoclonic movements. CTA showed marked progression in cerebral venous dilation (Figure 2D-F) compared to prior imaging, concerning for cerebral venous hypertension, again thought to be related to the dialysis graft. At this point this finding was considered to be the major underlying factor for her encephalopathy. MRI brain also showed prominent blood vessel seen on SWI sequences.

AV graft ligation was considered but delayed to allow medical stabilization. She developed sepsis due to urinary tract infection and had severe labile hypertension that required close monitoring and prolonged hospital course. Four weeks later, patient’s overall medical status improved as well as her encephalopathy, she was alert but oriented only to self, able to follow commands with rare myoclonic movements. Patient was discharged with planned for elective surgery 2 weeks later, although she was readmitted earlier for left temporal intracerebral hemorrhage.

Etiology of left temporal intracerebral hemorrhage was attributed to increased venous pressure, and the AV graft was ligated. One week later, cerebral angiography demonstrated improvement of the venous dilation (Figure 3, bold arrow) despite the presence of lack of visualization of left transverse sinus, deemed to be chronic due to small hypoplastic tranverse sinus that was prior seen in CT angiogram (Figure 3, dotted arrow). The patient’s mental status also improved, and 3 weeks after graft ligation she was fully alert and oriented, with normal attention and able to follow 2 steps commands; mild asterixis was still present At neurology clinic follow-up 3 and 6 months after graft ligation, her neurological examination showed further improvement with normal mental status by standard bedside testing and absence of abnormal movements.

Figure 3.

Angiogram post AV graft closure. A) LCCA. Anterior view, arterial phase. B) LCCA. Anterior view, venous phase, reduced venous engorgement (bold arrow), small hypoplastic transverse sinus (dotted arrow). C) LCCA. Lateral view, arterial phase. D) LCCA. Lateral view, venous phase. Reduced venous engorgement (bold arrow). R: right, L: left, A: anterior, P: posterior.

Discussion

The most important task for a neurologist in a patient with rapid change in cognitive status is to find and treat reversible causes. While conceptually simple, this can prove difficult in execution. The patient we describe illustrates this problem and highlights the importance of awareness of venous congestive encephalopathy related to hemodialysis grafts as a potential cause of a syndrome of progressive, fluctuating encephalopathy, stepwise decline, myoclonus, new-onset epilepsy, and imaging findings characteristic of cerebral venous hypertension.

Several case reports demonstrate that AV grafts, with direct access to the jugular vein, can result in venous engorgement, causing a variety of neurological symptoms including headache, visual changes and papilledema, gait instability, seizure, subdural hematoma, intracranial hemorrhages, and cognitive decline. A review of the literature yielded at least 15 publications reporting neurological signs and symptoms related to venous hypertension caused by altered cervical and cerebral blood flow from central vein access for hemodialysis.^1-15 Most of these cases clinically manifested with visual changes and papilledema suggesting a more typical presentation of elevated intracranial pressure, while others presented in a manner similar to our patient with seizures, hemorrhages, ischemic events, and encephalopathy. The time from venous access placement to onset of symptoms was extremely variable, suggesting that this condition needs to be considered in patients with such venous access regardless of when the procedure was performed as long as it is still patent. In almost all cases the surgical intervention on the vascular access used for dialysis lead to a complete resolution of the symptoms (Table 1)

Table 1.

Cases of Neurological Symptoms in Setting of Venous Hypertension Due to Vascular Access for Hemodialysis Patients.

First author	Signs and symptoms	Shunt type	Time to presentation from shunt creation	Treatment	Outcome
Molina JC	headache and progressive vision loss, papilledema	Right forearm AV graft	6 months	Ligation of the AV graft	Improved papilledema, no change in visual loss
Hartmann A	Headache, gait instability, memory loss	Left brachial AVF	27 years	Ligation of the AVF	Complete resolution
Nishimoto H	Headache and seizure	Left subclavian AVF	1 day after angioplasty	Ligation of the AVF	Complete resolution
Cuandra SA	Left eye blindness, reduced visual acuity in right eye, bil disc edema, decline in mental status	Right brachial artery to IJ graft	4-5 years	Graft occlusion	Complete resolution of encephalopathy, visual acuity and papilledema in OD, persisted reduced visual acuity in OS
Kornhuber ME	Bilateral visual loss	Right subclavian artery to IJ	9 months	None due to severe medical condition	Died from complication of pneumonia
Cleper R	Right eye vision loss, seizure, decerebrate posturing	Left brachio-basilic AVF	12 months	Ligation of the AVF	Severe brain damage and death
Nishijima H	Seizure, headache	Left brachial AVF	5 years	Ligation of AVF	Complete resolution.
Saha MK	Left parietal hemorrhage	Left cephalic to IJ graft	unclear	Occlusion of the graft	Complete resolution
Samaniego EA	Headache, AMS, drowsiness with right occipital stroke	Right AV graft	2 weeks	Occlusion of the graft	Complete resolution
Herzig DW	Case1: headache and blurry vision Case2: disorientation, seizure	Left brachial AVF	unclear	Ligation of AVF	Complete resolution
Simon MA	Progressive bil. blurry vision with optic disc edema	Right IJ catheter	Several months	Removal of catheter and angioplasty	Complete resolution
Mackav DD	Headache, blurry vision	Left HeRO graft	3 days	VP shunt placed—HeRO graft kept	Complete resolution
Prasad V	Left SDH and left ischemic stroke	Left AV graft	unclear	Venoplasty and endovascular stent repair	Complete resolution
deFraitas D	Bilateral visual loss	Right brachial to axillary AVF	unclear	Venoplasty and self expanding stent	Complete resolution
Haruma J	Seizure	Left brachio-cephalic AVF	4 years	In-stent angioplasty	Complete resolution

Legend: AVF: arteriovenous fistula; AV: arteriovenous; IJ: internal jugular; bil: bilateral; SDH: subdural hematoma; HeRO: hemodialysis reliable outflow; OD: right eye; OS: left eye.

The exact frequency of central venous access is unclear and depends on several factors.¹⁶ Despite the effort to limit the use of central venous access for HD patient, some of them eventually will required central access or have needed central access at the list once in their lives. In both cases that is an increased risk of developing central venous stenosis that will make patients at risk to develop venous hypertension. The prevalence of central venous disease in HD patient ranges widely from 20-50%^10,16,17,18 although not all of them will develop symptoms.

Our patient not only had the presence of stenosis of the right brachiocephalic vein due to prior fistula, but this was associated with reverse flow in the right IJ and presence of a hypoplastic left transverse sinus, that further impaired the cerebral venous drainage. These findings seem to be in line with a recently proposed “2-hit” hypothesis that suggests that the presence of increased venous intracranial flow needs to coexist with venous outflow impairment to become symptomatic.¹¹ It is possible that the presence of fluctuating encephalopathy was due to presence of hemodynamic fluctuations, although this cannot be confirmed. A similar clinical syndrome has been described in patients with dural AV fistulas, in which combined high flow through the AV shunt and associated outflow obstruction cause increased venous pressure that leads to progressive cognitive decline, reversible with surgical intervention.¹⁹ The presence of bedside fundoscopic examination remains a fundamental portion of the neuro exam that should always be assessed. In our case this was not performed initially because the venous hypertension was not recognized as possible cause of her symptoms and later due to technical difficulties.

Patients on HD often have several comorbidities, such as hypertension, electrolytes abnormalities, increased susceptibility to infections, that can confound the evaluation for other causes of cognitive decline that are, although rare, treatable and potentially more harming. Awareness of the clinical syndrome of venous congestive encephalopathy, well demonstrated by our case, is essential to its diagnosis. Although our patient had several competing causes for her encephalopathy, the lack of complete improvement after treatment of them was indicative of a different underlying etiology as the major cause of her cognitive decline. Conversely, lasting neurological improvement after AV graft closure confirmed that her syndrome was due to venous congestion. It is crucial to identify as soon as possible treatable condition such as venous congestive encephalopathy, to avoid long term deficit. Fortunately, despite delay in diagnosis and an intraparenchymal hemorrhage, our patient’s neurologic status still improved following ligation of the AV graft.