Isolated pontine involvement in posterior reversible encephalopathy syndrome with coincidental acute ischaemic stroke

Abstract

Posterior reversible encephalopathy syndrome (PRES) is a cliniconeuroradiological syndrome characterised by a unique reversible pattern on imaging and total regression of clinical symptoms and signs. We describe an unusual case of PRES with isolated pontine involvement with coincidental acute ischaemic stroke in a 60-year-old man who presented with headache, unsteadiness of gait, blurred vision and elevated blood pressure. MRI scan revealed an expanded pons with diffuse T2 and Fluid attenuated Inversion Recovery (FLAIR) hyperintensities and an acute infarct in the right temporal lobe. A diagnosis of PRES was considered most likely after exclusion of other differentials and the patient was started on antihypertensive treatment as for hypertensive encephalopathy. He became asymptomatic after controlling blood pressure and the follow-up MRI scan at 3 weeks showed complete resolution of the pontine high signals which confirmed the diagnosis of PRES.

Background

Isolated diffuse involvement of pons is rarely seen in posterior reversible encephalopathy syndrome (PRES). We report a patient with isolated pontine involvement of PRES and coincidental acute temporal lobe ischaemic infarction. This is a rare combination and there are few case reports in the medical literature about the brainstem variant of PRES and acute ischaemic infarctions. This case report emphasises the importance of awareness among the clinicians about the isolated pontine involvement in PRES and the possible coexistence of acute ischaemic strokes.

Case presentation

A 60-year-old man presenting with occipital headache for 6 weeks and sudden-onset dizziness, worsening of headache with nausea, restlessness, unsteadiness of gait and blurring of vision in both eyes of 1 day duration, was admitted to the Accident and Emergency unit. He denied any head injury, fever, weakness or numbness of limbs, seizures or speech problems.

He was a known patient with hypertension diagnosed 3 years ago and had stopped treatment himself for the last 2 years. He had no history of diabetes, chronic renal failure or connective tissue disorders and he was not a chronic alcohol user. He had not been on any regular medications including immunosuppressive drugs.

On arrival, his blood pressure was 215/127 mm Hg and the heart rate was 78 beats per minute. The oxygen saturation on air was 96%. He had unsteadiness of gait but there were no other cerebellar signs or any other focal neurological deficit suggestive of acute stroke. His visual acuity and visual field examinations were essentially normal and there was no papilloedema. He had no neck stiffness or other signs of meningism.

Investigations

Initial blood investigations were normal including inflammatory markers except serum creatinine which was 125 mmol/L. The 12-lead ECG was in sinus rhythm with changes of chronic hypertension. His blood sugar and magnesium levels were normal.

An urgent non-contrast CT scan showed a diffusely hypodense pons. Mild changes of chronic small vessel ischaemia were seen in the periventricular and deep white matter of both cerebral hemispheres. No other abnormality was seen (figure 1). He underwent a non-contrast MRI scan which demonstrated a small focus of restricted diffusion in the right posterior temporal lobe, consistent with an acute infarct (figure 2). In addition, the pons appeared expanded with generalised hyperintense signals on T2 and Fluid attenuated Inversion Recovery (FLAIR) sequences without any associated restricted diffusion or haemorrhage (figure 3).

Figure 1.

Non-contrast CT brain which showed the diffusely hypodense pons.

Figure 2.

Non-contrast MRI brain diffusion-weighted MRI (DWI) sequences which demonstrated a small focus of restricted diffusion in the right posterior temporal lobe, consistent with an acute infarct.

Figure 3.

The pons appeared expanded with generalised hyperintense signals on non-contrast MRI brain T2 and FLAIR sequences.

The transthoracic echocardiogram did not show valve abnormalities or intracardiac thrombus. The carotid and vertebral Dopplers did not show significant stenosis (less than 30% carotid stenosis in both sides according to North American Symptomatic Carotic Endarterectomy Trail (NASCET) grading). The ultrasound scan of the kidneys showed relatively small left kidney and demonstrated cortical thinning. Renal Dopplers were difficult to obtain on the left, but there appeared to be ‘Parvus et tardus’ waveforms. The appearances were suggestive of left renal artery stenosis.

Differential diagnosis

The signal changes of pons were strikingly unusual in appearance. The patient did not have any electrolyte imbalance or any history of correction of hyponatraemia, thus excluding central pontine myelinolysis. Moreover, the signal abnormality involved the entire pons rather than limiting to a central location, which also went against central pontine myelinolysis.¹

Other differential diagnoses of hyperintense lesion in the brainstem include tumours (gliomas and lymphomas), vasculitis, infections, multiple sclerosis or hepatic encephalopathy.² Pontine lesions may manifest as hemiplegia hemisensory deficit, bulbar dysfunction and vertigo which were absent in our patient.³ He was not a chronic alcohol user and did not have correction of hyponatraemia, clinical or biochemical evidence of hepatic encephalopathy, or features compatible with multiple sclerosis or infection. We considered pontine PRES as the most probable diagnosis with pontine glioma as a less likely differential.

Treatment

On the first day of admission, he was managed as hypertensive encephalopathy and started on oral antihypertensives, initially 10 mg amlodipine once a day with the target of reducing mean arterial pressure by 25% on day 1 as the CT did not show acute stroke. His blood pressure did not drop and then 4 mg doxazosin once daily on day 2 was added. However, at the end of 48 hours, he had persistently elevated blood pressure above 200/110 mm Hg and he was continuously symptomatic. So, it was decided to start him on glyceryl trinitrate infusion (GTN). By then, the MRI of the head was available, and we decided to follow the stroke guidelines to control blood pressure and subsequently 1.5 mg indapamide once a day and 50 mg atenolol were added while weaning off from GTN infusion by day 4. When his blood pressure was controlled by day 4 of admission, his symptoms completely disappeared. After MRI of the head, he was started on 300 mg of aspirin daily and changed to 75 mg clopidogrel once daily on discharge on day 6. He was started on 40 mg atorvastatin on day 3. We did not start him on an ACE inhibitor or angiotensin receptor blocker due to the high possibility of renovascular hypertension as he developed severe hypertension at a later age, and because of the ultrasound imaging findings.

Outcome and follow-up

Once his blood pressure was controlled, almost all his symptoms were resolved. Three weeks after the initial presentation, he underwent a contrast MRI scan. There was almost complete resolution of the pontine signal abnormality. No enhancement was seen in the pons following contrast administration. The small infarct in the right temporal lobe was seen again. These findings confirmed the diagnosis of PRES (figure 4) with coincidental acute ischaemic stroke.

Figure 4.

Follow-up contrast-enhanced MRI brain which demonstrated almost complete resolution of the pontine signal abnormality. Small infarct in the right temporal lobe was seen again.

We arranged 24 hours ECG tap, and renal and cerebral CT angiograms during the follow-up but, unfortunately he was lost to follow-up.

Discussion

PRES was first described by Hinchey in 1996 as a reversible neurotoxic syndrome manifested with acute onset of headache, alteration of level of consciousness, seizures, visual field defects and associated white matter changes predominantly affecting posterior parietal and occipital lobes of the brain. Wide varieties of medical conditions have been implicated as causes of PRES such as hypertensive encephalopathy, eclampsia, immunosuppressive therapy, renal failure, acute intermittent porphyria and thrombotic thrombocytopenia purpura.⁴

Even though the exact pathogenesis of this condition is unknown, there are two theories to explain the pathological findings. According to the first hypothesis, which is widely accepted, the vascular leakage and vasogenic oedema is caused by elevation of blood pressure above the cerebral autoregulation. The second theory suggests that this syndrome is triggered by endothelial dysfunction caused by circulating either endogenous (as seen in pre-eclampsia and sepsis) or exogenic (such as chemotherapy and immunosuppressive agents) toxins.⁵ The predominantly posterior distribution can be explained on the grounds of better developed sympathetic innervations and autoregulation in the anterior circulation.⁶

There are no specific diagnostic criteria for PRES. In the appropriate clinical setting, MRI brain adds considerable diagnostic information. Most commonly described abnormalities consist of symmetrical cortical and subcortical hyperintense signals on T2-weighted and FLAIR-weighted sequences. The most commonly affected region is the parieto-occipital lobe followed by the frontal lobes, basal ganglia, cerebellum, brainstem and thalamus.⁷ Even though the central variant of PRES is widely described, infratentorial involvement and particularly diffuse involvement of the pons is rare.⁸ There are anecdotal case reports in the medical literature with isolated brainstem involvement in PRES and concomitant acute ischaemic cerebral infarctions.⁹

The treatment of PRES is basically symptomatic and managing the underlying condition as there is no specific therapeutic strategy currently available.¹⁰ However, it is very important to recognise it promptly since the neurological dysfunction is usually reversible with appropriate treatment.

When a patient presents with PRES with high blood pressure, as in our patient, there are no evidence-based prospective controlled studies to support strict blood pressure control to reverse the neurological sequalae. A reduction of blood pressure by 25% from baseline is recommended using antihypertensive medications as per hypertensive emergency while avoiding blood pressure fluctuations.¹¹ However, this is more complex when the patient has got a concomitant stroke. In a Cochrane review, it has been shown that lowering blood pressure in patients with acute stroke, regardless of aetiology, has failed to improve the outcome. More importantly, more than 20% fall in blood pressure within 48 hours of onset has been associated with poor outcome.¹² Therefore, most guidelines suggest postponing treatment for hypertension by days to weeks unless the blood pressure is more than 220/120 mm Hg, or more than 200/100 mm Hg with concomitant acute kidney injury, encephalopathy, aortic dissection, haemorrhagic stroke, pulmonary oedema or cardiac injury. Our working diagnosis was hypertensive encephalopathy and he was managed with oral antihypertensives, initially 10 mg of amlodipine once a day with the target of reducing the mean arterial pressure by 25% on day 1 as the CT did not show acute stroke. The longer the time taken to control the causative factor such as hypertension and hyperglycaemia adversely affect the 90-day functional outcome and mortality in PRES.¹³ Therefore, some patients may warrant intravenous antihypertensives with continuous haemodynamic monitoring.

Patients with PRES may present with seizures that are usually generalised tonic-clonic type and there is a tendency for recurrence. They need anticonvulsive therapy frequently. However, there are no recommendations for specific anticonvulsive drugs or optimal duration of anticonvulsive therapy. Usually, anticonvulsive therapy can be weaned off once the patient is asymptomatic and the imaging findings are reversed.¹⁴ A high number of patients with PRES have been found to have low magnesium levels. As magnesium has got prophylactic anticonvulsive and vasodilating effects, hypomagnesaemia should be avoided and magnesium levels should be maintained in the high normal range.¹¹

Our patient presented with hypertensive emergency and the onset of hypertension was after the age of 50 years. The findings of the ultrasound scan of the kidneys suggested possible renovascular hypertension. In such a situation, antihypertensives of choice are calcium channel blockers and β blockers, while ACE inhibitors and angiotensin receptor blockers should be avoided. Renal angiography and angioplasty should be considered for patients with PRES and malignant hypertension.¹⁵

Learning points.

• If a patient presents with elevated blood pressure with neurological symptoms and signs, possibility of posterior reversible encephalopathy syndrome (PRES) should also be considered.

• Isolated infratentorial involvement in MRI head with compatible clinical symptoms and signs should raise the possibility of PRES even though it commonly presents as a reversible vasogenic oedema predominantly affecting the posterior parieto-occipital region. Follow-up MRI is important to exclude other differential diagnosis for diffuse infratentorial involvement.

• It is important to be aware of the possibility of coincidental ischaemic stroke together with PRES.

• If a patient with PRES has got a coincidental acute ischaemic stroke, blood pressure should be controlled as for hypertensive emergency with acute ischaemic stroke.