Surgical treatment of severe Posterior Reversible Encephalopathy Syndrome (PRES) with brainstem involvement: Systematic Review and Illustrative Case

doi:10.21203/rs.3.rs-3740002/v1

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Surgical treatment of severe Posterior Reversible Encephalopathy Syndrome (PRES) with brainstem involvement: Systematic Review and Illustrative Case

https://doi.org/10.21203/rs.3.rs-3740002/v1

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Background and Purpose – Untreated hypertension can lead to severe posterior reversible encephalopathy syndrome (PRES), that is a reversible intracranial complication. Involvement of posterior fossa structures including brainstem is extremely rare but life-threatening condition if not treated properly and timely. Here we review different clinical aspects of surgically treated cases of PRES with brainstem involvement and present an illustrative case.

Methods – We searched the MEDLINE electronic database for studies on PRES with brainstem involvement. Hypertensive crisis as a cause of PRES and surgical treatment of PRES were inclusion criteria. We show a successfully treated case with this constellation. Finally, we summarize the data in current literature to provide treatment recommendation for this rare devastating condition.

Results – We found 5 reports with a total of 7 patients of PRES with brainstem involvement which were treated by posterior fossa decompression. Hypertension or malignant hypertension were common at onset of PRES. 85% of all cases were females and one of these cases was a 3-year-old girl. 71% of patients had a mRS ≤ 3 at discharge.

Conclusions – A clinically manifest brainstem PRES can be alleviated successfully through posterior fossa decompression so the ischemic and oedematous brain tissue can regenerate without further injury due to mechanical compression.

posterior reversible encephalopathy syndrome

hypertensive crisis

Brainstem ischaemia

Cerebellar ischaemia

surgical treatment

decompression

The severe posterior reversible encephalopathy syndrome (PRES) is a neurological emergency that requires emergent medical and in rare cases the surgical treatment^{1, 2}. This condition was initially described in 1996¹ as a clinical-neuroradiological syndrome as a result of hypertensive emergency.^{2, 3} PRES includes the clinical symptoms of nausea, vomiting, headache, visual disturbances, seizures, altered mental status and focal neurologic deficits such as contralateral hemiparesis.⁴ In neuroimaging, PRES presents as malignant oedema, which appears as a hypodense lesion in cranial computed tomography (cCT) and as a hyperintense area in in the T₂- weighted magnetic resonance imaging (MRI).^{1, 2, 5} These lesions are usually localized in the posterior parts of the brain such as the parieto-occipital cortex, cerebellum or the brainstem.^{2, 5} The pathomechanism involves vasospasms and edematous changes to the vascular walls. Distal to vascular stenosis, there is decreased perfusion of brain tissue, and development of stroke-like symptoms.^{5, 6, 7, 8} PRES in supratentorial region in a stable clinical condition can be successfully treated through medication with the goal of a careful and slowly tapering off hypertension under strict monitoring. However, a severe cerebellar and brainstem PRES with severe edema can rapidly lead to mechanical compression due to very limited space in the posterior fossa. Radiological picture seems like an infarction of brain stem, but the CT angiogram show a largely normal patency of vessels. Depending on the severity of severe PRES fourth ventricle can be compressed with a consecutive hydrocephalus. The patients usually present with deep coma. Swelling and mechanical compression of brain stem can end lethally and need rapid decision making for the surgical decompression of posterior fossa to prevent mechanical injury^1–11. Here we review different clinical aspects including clinical outcome of the surgically treated cases of severe brainstem and cerebellar PRES and present an illustrative case of posterior fossa PRES involving brain stem and cerebellum clinically presented with deep coma and was treated with surgical decompression of posterior fossa.

Literature Search:

The MEDLINE database was used to search for literature using the following keywords: posterior reversible encephalopathy syndrome, hypertensive crisis, brainstem ischemia, cerebellar ischemia, surgical therapy, decompression. In total, 2800 articles were found, but only 15 of those articles included surgical treatment. Only seven of these presented with brain stem involvement. The relation between PRES and hypertension was only emphasized in 4 articles. As a result, the data analysis primarily focused on articles related to hypertension, brainstem involvement, surgical therapy, and the main diagnosis of PRES.

Analyzing the reference section of each publication did not provide any additional relevant articles. The systematic review was performed following PRISMA guidelines (Fig. 1). The reasons for excluding the reports were "no surgical treatment" (reason 1), "surgical treatment without brainstem involvement" (reason 2) and finally "brainstem involvement without hypertension" (reason 3). The database analysis mentioned here was exclusively conducted by first and last authors. In addition, we present a case with severe brain stem PRES with posterior fossa involvement that was successfully treated surgically.

Ethical Approval:

Approval from local ethical committee for review and analysis of data from the literature was not required. The patient with PRES admitted to our hospital gave informed consent for the publication of case and radiological images.

Case Report and Treatment:

A 66-year-old female patient with a GCS of 3 was presented at our Neurosurgical Department. Previously, she had experienced a generalized tonic-clonic seizure and had a focal gaze to the left. She had an NIHSS of 9 with concomitant hypertensive derangement and systolic blood pressure values of 235 mmHg.

Cranial computed tomography (cCT) showed bioccipital, subcortical, and bilateral hypodense lesions in the cerebellum, medulla oblongata and pons covering most of areas perfused by the posterior inferior cerebellar artery (PICA) and the anterior inferior cerebellar artery (AICA). Infratentorial swelling lead to compression of the fourth ventricle and resulted in acute hydrocephalic occlusion (Fig. 2 a, b). No contrast deposits were visible, pointing towards vasogenic edema. Haemorrhages and fractures of the cranial vault were ruled out. Computed tomography angiography (CTA) and perfusion CT showed no further pathological findings.

In addition to pharmacological therapy, surgical suboccipital bilateral decompression with expanded duraplasty was performed to reduce intracranial pressure and to relieve mechanical pressure on the 4th ventricle (Fig. 3 a-d). Additionally an external ventricular drainage (EVD) was placed to relieve hydrocephalus and to monitor the patient. Blood pressure was slowly tapered off over a week.

After several weeks of intensive medical care antihypertensive and anti-epileptic medication, the patient was sent for rehabilitation. At discharge the patient had a mRS of 3 and at 3 months follow up the patient did not show any neurological symptoms and the initial symptoms were completely subsided (mRS of 0). Radiological follow-up after a few weeks showed no pathologies and clinical tests did not reveal any new neurological deficits. A long-term follow up one year showed no neurological symptoms (mRS 1) and anti-epileptic medication was tapered off.

Literature Review:

We found 5 reports featuring 6 patients of PRES (3 with malignant hypertension, 3 with hypertension). Most reported cases had brainstem and cerebellar involvement. The clinical features of all cases has been summarized in table 1 (Table 1). The clinical data on age, sex, location of the injury, initial blood pressure, symptoms, history of hypertension, initial GCS, and the mRS at discharge was evaluated and compared with our case. Approximately 85.71% of the here analysed patients were female. Half of all patients had initial hypertensive crisis with malignant hypertension (57.67%) and the other half had a history of hypertension and presented with hypertension. Commonly observed symptoms in patients were unconsciousness, progressive somnolence, sudden onset of nausea, agitation, confusion, slurred speech, headache, nystagmus, vertigo, cranial nerve deficits, ataxia, and hemiparesis. Four out of six patients developed a severe loss of consciousness upon arrival in the emergency department. The level of consciousness as graded by the Glasgow Coma Scale (GCS) was less than 9 in 71.42% of the here described cases. The other two cases had a GCS of 12 and 13 points at arrival.

An adequate therapeutic approach for decompression of the posterior fossa is shown in Fig. 4.

Clinical Outcome:

The clinical outcome of patients was classified according to the modified Rankin Scale (mRS). Half of the patients had a mild or no impairment at discharge. Two out of seven (28,57%) patients had severe neurological impairment and required assistance to cope with daily living. One of the patients required palliative care.

Only seven cases of PRES involving brain stem treated surgically have been reported in world literature. All of the six cases of already reported cases of PRES had a history of hypertension and presented with hypertension or with a severe resistant hypertensive crisis (Table 1). The majority of cases presented in literature were females who presented with reduced consciousness. All patients reached a favourable clinical outcome at discharge (mRS of 3 or better than 3). The data reported in literature is very similar to our case. Our patient was a female with who presented with a malignant hypertension and loss of consciousness. Surgical decompression of posterior fossa, implantation of EVD and combination of antihypertensive and anti-epileptic pharmacotherapy yielded a fairly good clinical outcome at discharge and complete normalization of symptoms at 3 months follow up.

The pathomechanism behind severe posterior reversible encephalopathy syndrome (PRES) is not yet fully understood. However, most of the PRES cases have elevated blood pressure. It is hypothesized that the sudden increase in blood pressure leads to hyperperfusion of the brain, resulting in capillary leakage and edema formation in the brain parenchyma. Symptoms occur depending on the location of the swelling with the posterior fossa being the most common one. PRES is diagnosed clinically as well as radiologically. Patients present with pathological cranial CT or MRI in addition to sudden onset of neurological deficits. Timely combined medical and surgical treatment are critical for the clinical outcome of patients. Surgical treatment allows the edematous brain parenchyma to regress without further compression and mechanical injury.

More than seventy percent of reported patients had a GCS score lower than 9 initially. The affected brain areas were nearly identical in PRES patients with hypertension. All the analysed patients had cerebellar, 83.33% brainstem and approximately forty percent occipital lobe involvement. These patients were admitted with coma and intubated prior to surgery. Our patient presented with a GCS of 3 and was immediately intubated and due to severe cerebellar and brainstem PRES with compression of fourth ventricle sent for emergent surgery.

About fifty percent of the here described patients had a history of manifest hypertension prior to PRES, which is a known high-risk factor for cerebral vasospasm and haemorrhagic insults.

The clinical symptoms of in literature reported patients were diverse with various severity of loss of consciousness, vomiting, severe headache, dizziness, confusion, seizures, agitation and generally developed disturbances of consciousness, pointing towards brain and brainstem injury.

Gender seems to be another factor, because 83.33% of the patients are female, including a 3-year-old girl. There also seems to be a correlation with age as seventy percent of patients were over the age of 50. Our patient had very similar findings being a female with an age above 50 years.

Most of the patients were discharged a few weeks after surgical decompression of the posterior fossa. At discharge, most of them had no neurological deficits (mRS 0).

There are certain limitation in the review of reported cases. First of all, the lack of report on initial blood pressure and vital parameter data in cases reported by Brooks et al. This review only addressed symptoms, localization of edema, therapy, and clinical assessment. Another limitation is that all studies did not address the baseline mRS, but only the mRS score at discharge which points towards PRES being the only cause of neurological impairment. All patients were treated by surgical decompression of the posterior fossa. The combination of medical and surgical therapy provided the optimal results as patients could resume their daily life a few weeks after treatment.

Severe posterior fossa PRES with brainstem involvement need rapid decision making for emergent surgical decompression of posterior fossa to reduce the mechanical injury to brainstem due to prolonged compression with ultimate goal to facilitate regeneration of brainstem without further injury. Most of the patients with brainstem PRES treated with combination of medical and surgical management recovered a few weeks after surgical decompression. Therapeutic decisions about severe PRES should consider the risk of herniation of brain tissue. Quick and efficient treatment in such cases ensures better quality of life of patients (Figure 4).

Disclosures statement

I. Funding Sources:

This research project received financial support from Department of Neurosurgery, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany. However, the funding body had no role in the study design, data collection, analysis, interpretation, or the decision to publish.

II. Employment Affiliations:

Author Ronahi Lala is affiliated with Department of Neurosurgery, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany. The employer was not involved in the design, conduct, analysis, or reporting of this study.

III. Consultancies and Honoraria:

None of the authors received any consultancies or honoraria related to this systematic review.

IV. Financial Interests:

The authors declare no financial interests, direct or indirect, that could be perceived as influencing the findings or conclusions presented in this systematic review.

V. Personal Relationships:

There are no personal relationships with individuals or organizations that could have influenced the outcome of this study.

VI. Competing Products:

None of the authors have any competing products or competing interests that could be associated with this research.

VII. Non-Financial Conflicts:

The authors declare no financial conflicts of interest that may have influenced the study design, data collection, analysis, or interpretation of results.

VIII. The systematic review has been conducted with the highest level of integrity and adherence to accepted research standards, ensuring transparency, objectivity, and unbiased reporting of the findings.

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Table 1 is available in the Supplementary Files section.

No competing interests reported.

PRESManuscriptFinale231111table.pdf

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Surgical treatment of severe Posterior Reversible Encephalopathy Syndrome (PRES) with brainstem involvement: Systematic Review and Illustrative Case

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