Disc Oedema in A Patient with Chronic Kidney Disease: A Diagnostic Conundrum

ABSTRACT

A 47-year-old woman who presented with headache and blurring of vision was referred to us due to suspicion of idiopathic intracranial hypertension or cerebral sinus venous thrombosis. She had chronic kidney disease and underwent dialysis through multiple ports including the right internal jugular vein (IJV). Her examination showed a best corrected visual acuity of 20/20 in each eye, normal anterior segments in each eye but bilateral papilloedema. Magnetic resonance imaging and venography (MRV) of her brain with contrast showed signs of raised intracranial pressure and a hypoplastic left transverse sinus. An MRV of her neck showed a thrombosis of the right IJV. Her symptoms and papilloedema resolved with carbonic anhydrase inhibitors and anticoagulants. This case highlights an uncommon presentation of papilloedema secondary to raised intracranial pressure from IJV thrombosis and its pathogenesis.

Introduction

Cerebral sinus venous thrombosis (CSVT) is an uncommon form of venous thrombotic disease that often presents with acute neurological symptoms including headaches, seizures, altered sensorium, aphasia, stupor, coma, and visual field defects.¹ Thrombosis may occur at multiple sites; however, the transverse and superior sagittal sinuses are most frequently affected. Internal jugular vein (IJV) thrombosis accounts for 12% of these cases^1,2 and can lead to reduced venous return from the head resulting in secondary intracranial hypertension (ICH) mimicking idiopathic intracranial hypertension. We herein describe a case of a patient with chronic renal failure who had a long-standing indwelling dialysis line in the right IJV and developed a thrombosis in that vein, causing a diagnostic and management dilemma.

Case presentation

A 47-year-old, non-obese woman was referred to our institute by her neurologist for evaluation of headaches and blurring of vision in both eyes for distance and near for 20 days. The headaches were holocranial, diffuse and were slightly worse in the morning. She also reported associated transient visual obscurations for the same amount of time, but denied vomiting, tinnitus, or increased headache on bending forwards. She denied recent weight gain and was not on any drugs associated with causing ICH. Her neurologist had detected bilateral papilloedema and suspected her to have either idiopathic intracranial hypertension (IIH) or a CSVT. She was referred for a Neuro-ophthalmology opinion prior to obtaining neuroimaging and further work-up. She had been diagnosed with diabetes mellitus and arterial hypertension 20 years ago and had been on haemodialysis for chronic kidney disease (CKD) for the previous 18 months. The haemodialysis was being administered with indwelling catheters through from multiple ports, initially from the right IJV and more recently through a left radio-cephalic arterio-venous fistula.

Her examination showed a best corrected visual acuity (BCVA) of 20/20 in each eye (OU), normal colour vision (17/17 of the Ishihara plates OU), normal anterior segments OU, no relative afferent pupillary defect, and full extra-ocular motility OU. Fundus examination revealed 360° disc oedema, with disc hyperaemia and opacification of the peripapillary retinal nerve fibre layer OU (Figure 1). There were also microaneurysms, hard exudates, flame-shaped and dot and blot haemorrhages suggestive of non-proliferative diabetic retinopathy OU (Figure 1). Automated perimetry showed enlarged blind spots in both eyes with superior and inferior arcuate scotomas in the right eye and early nasal defects in the left eye (LE) (Figure 2). Her arterial blood pressure was 120/80 mmHg.

Figure 1.

Fundus photographs showing 360-degree disc oedema with blurring of the peripapillary retinal nerve fibre layer in both eyes (white dotted arcs), and a few flame-shaped haemorrhages in the right eye (white asterisk). There were also microaneurysms, hard exudates, and flame-shaped and dot and blot haemorrhages in the background suggestive of non-proliferative diabetic retinopathy in both eyes. Note the obscuration of blood vessels at the disc margin at presentation in the left eye (white arrowheads).

Figure 2.

Automated perimetry performed using the 24–2 Swedish interactive threshold algorithm-FAST 24–2 testing strategy in both eyes showing enlargement of the blind spots (black circles) with superior and inferior arcuate scotomas in the right eye and nasal depression in the left eye (black arrow).

Magnetic resonance imaging (MRI) with magnetic resonance venography (MRV) of her brain and neck with contrast occurred after consulting her nephrologist as her serum creatinine was 10.3 mg/dl. She underwent haemodialysis on the day of the MRI. The imaging showed flattening of the posterior sclera, with prominent cerebrospinal fluid (CSF) spaces (Figure 3a) along both optic nerves suggestive of ICH. The MRV of her brain showed reduced calibre of the left transverse sinus (Figure 3b). The MRV of her neck showed non-visualisation and thrombosis of an 8.1 cm segment of the right IJV at its mid and distal portions until the confluence into the right subclavian vein (Figure 4 and online supplementary Video 1).

Figure 3.

(a) Contrast-enhanced MRI brain showing flattening of the posterior sclera (white arrows) and increased perioptic nerve sheaths (white asterisk), suggestive of ICH. (b) MRV brain showing a hypoplastic left transverse sinus (white arrowhead).

Figure 4.

Contrast enhanced MRV neck showing normal flow in the right transverse and sigmoid sinuses (white arrows) whilst there is lack of flow in the right IJV (white dotted line) suggestive of thrombosis. See the calibre of the left IJV for comparison (white arrowhead).

Given the long segment of IJV thrombosis and the absence of any clinical or radiological signs of meningitis a lumbar puncture was not performed. Her other relevant investigations are listed in Table 1.

Table 1.

Relevant laboratory investigations at presentation

Laboratory parameter	Patient value at presentation	Reference range
Haemoglobin	11.3 g/dL	11.5–15.5 g/dL
Total red blood cell count	4.37 x 106/mm3	4.5–6.5 x 106/mm3
Mean corpuscular volume	78.7 fL	82–92 fL
Mean corpuscular haemoglobin	25.9 pg	27–32 pg
Mean corpuscular haemoglobin concentration	32.8%	32–36%
Blood urea	194 mg/dL	0–40 mg/dL
Serum creatinine	15.0 mg/dL	0.6–1.4 mg/dL
Serum potassium	2.8 meq/L	3.5 − 5.5 meq/L
Serum sodium	134 meq/L	135–150 meq/L
Serum chloride	103 meq/L	90–106 meq/L
Fasting blood glucose	114 mg/dL	60–100 mg/dL

She was managed in consultation with her neurologist and nephrologist and was started on acetazolamide 500 mg/day and acenocoumarol 2 mg/day with monitoring of her visual function, prothrombin time and international normalised ratio. At 12-weeks’ follow-up, her best corrected visual acuity was 20/20 OU, colour vision was 17/17 of the Ishihara plates OU, and her pupils were equally briskly reacting. Fundus examination showed interval reduction of the disc oedema (Figure 5) and automated perimetry showed interval reduction in the enlarged blind spots and nasal depression (Figure 6). She was continued on acetazolamide 500 mg/day and acenocoumarol 2 mg/day. At her last follow-up (6 months later), her visual function was stable, with near complete resolution of the disc oedema OU. Automated perimetry showed mild peripheral constriction. The acetazolamide was reduced to 250 mg/day and the acenocoumarol was continued as per the advice of her neurologist.

Figure 5.

Fundus photographs at 3 months’ follow-up showing interval reduction of the disc oedema in both eyes (white dotted arcs showing minimal blurring of the peripapillary retinal nerve fibre layer). Note the obscuration of the blood vessels at the disc margins at presentation in Figure 1 has now resolved (white arrowheads).

Figure 6.

Perimetry after 3 months showing improvement with only mild enlargement of the blind spot in the left eye (black circles) and nasal depression in the right eye. Note the interval improvement in the nasal depression in the left eye (black arrow).

Discussion

This case report highlights an uncommon situation where papilloedema occurred secondary to IJV thrombosis in a patient with a long-standing IJV catheter for haemodialysis.

The chief differential diagnoses in a patient with CKD and bilateral disc oedema and prior CKD are highlighted in Table 2.^1,3–10 Our patient did not have any acute signs apart from papilloedema and it was difficult to distinguish clinically between cerebral venous sinus thrombosis (CVST) and an IJV thrombosis, except the presence of the risk factor of the long-standing indwelling catheter. Various factors such as tunnelled dialysis catheters,^11,12 Haemodialysis Reliable Outflow (HeRO) grafts,⁶ and hypercoagulable states^13,14 have been reportedly associated with IJV thrombosis. Reported occurrence of IJV thrombosis varies from 14% to 66% with indwelling IJV catheters.^3,11

Table 2.

Differential diagnosis of disc oedema in a patient with CKD

		Relevance to our patient
Aetiology	Clinical features	Points in favour	Points against
Malignant hypertension/ Hypertensive optic neuropathy	Prior history of systemic hypertension Recent history of fluctuation of arterial blood pressure/accelerated course Generally good visual function Bilateral disc oedema, presence of hard exudates, soft exudates, multiple haemorrhages, and attenuated blood vessels with disc edema even in absence of other features	Known hypertensive for the past 20 years Good visual function Presentation with headache and bilateral disc oedema	Arterial blood pressure under control by measurement and from the medical records Mild narrowing of blood vessels and lack of any other signs of hypertensive retinopathy/malignant hypertension No ECG changes suggestive of acute ischaemia
Diabetic papillopathy	Prior history of diabetes mellitus with usually a history of worsening of diabetes control Good to near normal visual function More commonly associated with bilateral diabetic retinopathy changes	Known diabetic for the 20 years Good visual function and bilateral presentation Associated moderate NPDR	Good glycaemic control as per documented reports and evaluation Moderate NPDR but no marked diabetic retinopathy changes Symptoms of elevated ICP (headache and TVOs)
Non-arteritic anterior ischaemic optic neuropathy	Prior history of vasculopathic risk factors Small crowded disc Haemodialysis may precipitate NAION Sudden change in vision or visual fields Associated localised focal or diffuse attenuation of blood vessels Classical visual field defects are altitudinal or arcuate, however inferior nasal defects possible	Prior history of vasculopathic risk factors	Gradual onset Headache and TVOs Blurred vision but no acute change in vision or visual fields Field defect suggestive of enlargement of the blind spots and nasal depression in both eyes
Uraemic optic neuropathy	Bilateral acute vision loss in patients with massive elevation of serum urea and creatinine levels Clinically presents as severe optic neuropathy with swelling of the discs and limited extension of oedema into the surrounding retina There might be mild retinal oedema as well Serum urea usually greater than 35.7 mmol/L (100 mg/dL) Prompt response to dialysis and systemic corticosteroids	Bilateral involvement Serum urea greater than 100 mg/dl at presentation	Insidious onset of vision disturbance; more like TVOs rather than acute vision change Symptoms of elevated ICP – headache and TVOs Bilateral disc oedema but no associated marked retinal changes Visual field defect suggestive of elevated ICP
Idiopathic/secondary intracranial hypertension	Gradual to subacute onset blurred vision Symptoms of elevated ICP (headache, TVOs, pulsatile tinnitus, diplopia, cranial nerve palsies) Associated bilateral disc oedema with good visual function Radiological signs of elevated ICP Usually seen in young women in the setting of IIH May see secondary raised ICP in patients on drugs such as tetracyclines and vitamin A derivatives No thrombosis on MRV brain/neck	Gradual onset Symptoms of elevated ICP Bilateral disc oedema with good visual function Radiological signs of increased intracranial pressure	Middle-aged non-obese woman No other drug intake reported to cause elevated ICP Definite thrombosis in the right IJV
Cerebral sinus venous thrombosis	Chronic CSVT similar presentation like idiopathic/secondary intracranial hypertension Definite thrombosis of at least one of the venous sinuses Acute/subacute forms might have associated seizures/stroke/encephalopathy	Same as above for IIH	Lack of acute signs: seizures; confusion; focal neurological deficits or altered mental status Chronic CSVT could not be ruled out however, MRV did not show thrombosis of any of the venous sinuses, only a hypoplastic left transverse sinus
Thrombosis of central neck veins/HeRO graft related thrombosis	Acute cases present with neck pain, swelling, erythema of the neck However, patients with subacute/chronic IJV thrombosis can present with isolated raised ICP Prior history of dialysis from a central vein port or HeRO graft especially for long periods	Same as above for IIH History of haemodialysis from the IJV catheter	Not applicable

CVST: Cerebral sinus venous thrombosis

ECG: Electrocardiogram

HeRO: Haemodialysis Reliable Outflow

ICP: Intracranial pressure

IIH: Idiopathic intracranial hypertension

IJV: Internal jugular vein

MRV: magnetic resonance venography

NPDR: Non-proliferative diabetic retinopathy

NAION: Non-arteritic anterior ischaemic optic neuropathy

TVOs: Transient visual obscurations.

In patients with indwelling or haemodialysis catheters, the reported pathophysiological mechanisms for development of thrombosis include physical presence of the catheter acting as a nidus, the effect of the material of the catheter, tip position, secondary infection, and any previous catheterisation.¹⁵ These factors might have contributed to the thrombosis in the right IJV in our patient.

The prevalence of visual complaints and papilloedema is relatively less common in patients with IJV thrombosis. Taban et al. reported among 44 patients with peripheral AV fistulas none of the patients had optic disc oedema or symptoms of ICH.¹⁶

Simon et al. suggested that a two-hit hypothesis, i.e. a combined effect of elevated central venous flow/pressure from a patent AV fistula and superimposed thrombosis in the IJV are necessary for the development of papilloedema and ICH.¹⁷

Our patient had a long-standing haemodialysis catheter that would have caused increased venous flow initially leading to turbulence and damage to endothelium, and a radiologically demonstrable thrombosis in the same vein, possibly meeting the requirements as per the above hypothesis. We hypothesise that in our case thrombosis in the right IJV coupled with hypoplasia of left transverse sinus impeded venous return from the brain from both sides resulting in secondary ICH and papilloedema similar to hypothesis by Simon et al.¹⁷ and the report by Thandra et al.¹⁰

Surprisingly, our patient did not show increased collaterals on the MRV neck, but we hypothesise that this is possibly due to the subacute development, which allowed partial venous drainage from the contralateral hypoplastic left transverse sinus and the left IJV. However, given a long segment of thrombosis in the right IJV it was still the likely aetiology of the ICH.

Management goals in our patient were promoting resolution of the IJV thrombosis with anticoagulants and prevention of vision loss by hastening resolution of papilloedema. In our patient, the IJV catheter had already been removed. Options of medical management and CSF diversion procedure (only in case of worsening despite maximal permissible medical therapy) were considered. Given patient choice and her poor surgical profile due to co-morbidities, we attempted medical management first in coordination with her nephrologist. Fortunately, the patient responded well, and her disc oedema resolved. The long-term management plan was to keep her on anti-coagulants for a period of at least one year and acetazolamide until there had been complete resolution of the disc oedema while monitoring her visual function. A repeat MRV was planned after one year of anti-coagulant therapy, keeping in view the difficulty in planning the imaging with concurrent dialysis.

As highlighted above, some limitations in our patient workup were not obtaining the lumbar puncture opening pressure and thrombotic profile. As we could rule out most other causes of optic neuropathy in our patient (Table 2) and given the temporal profile of our patient course, an IJV thrombosis secondary to the long-standing IJV catheter was the most likely cause of her papilloedema. However, co-existing systemic thrombotic abnormalities could not be ruled out.

Our case posed a both diagnostic and management dilemma. Keeping in mind various diagnostic considerations, CSVT and IJV thrombosis were most likely aetiologies. While both conditions need systemic anti-coagulants anti-oedema measures, acetazolamide, and might need CSF diversion procedures, patients with IJV thrombosis might need additional removal of an indwelling catheter.

Although acute CSVT and IJV thrombosis have distinguishing clinical associations, in the absence of any acute/localising sings, it was not possible to differentiate between the two aetiologies in our patient. The following features prompted suspicion of CSVT/IJV thrombosis instead of IIH: older age; lack of obesity and the prior history of CKD. Further, her prior history of a long-standing central venous catheter for haemodialysis prompted us to order an MRV neck in the initial setting that established the diagnosis of IJV thrombosis. Her co-morbidities and renal function posed challenges in her further evaluation and management. This case report highlights the need for suspecting neck vein thrombosis, obtaining appropriate work up including MRV brain and neck in patients with long-standing central vein catheter, and coordinating care of the patient with multiple specialists.

Funding Statement

Hyderabad Eye Research Foundation (HERF), Hyderabad, Telangana, India (no specific grant).