Posterior Reversible Encephalopathy Syndrome Due to Spinal Pathologies or Interventions

Abstract

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity characterized by headache, seizures, visual deterioration, motor and cognitive deficits, and decreased level of consciousness among other symptoms and signs with imaging findings suggestive of vasogenic edema preferentially affecting the occipital and posterior temporal and parietal lobes. As the name suggests in the vast majority of cases, the syndrome is self-limiting and the deficits are reversible to a large extent. It is seen most commonly in periparturient patients and multiple theories have been proposed regarding its pathogenesis. It is widely thought to occur due to intermittent high blood pressures overwhelming the myogenic arm of cerebral autoregulation and in the setting of weaker neurogenic autoregulation in the posterior cerebral circulation being due to sparse innervation; the resulting hyperperfusion creates vasogenic edema. This can be compounded by deranged overcompensation causing hypoperfusion and endothelial dysfunction precipitating vasogenic edema through increased permeability. Various spinal pathologies and interventions can create pathophysiologic cascades that can combine to result in PRES; thus leading to often unforeseen morbidity. This review seeks to present in a narrative form (systematically searched literature) on PRES as a sequel to spinal pathologies or interventions.

INTRODUCTION

Posterior reversible encephalopathy syndrome (PRES) is an increasingly recognized pathology first described by Hinchey et al.^[1] and is a dysfunction of the cerebral microcirculation. It can present with a wide array of symptoms and signs ranging from occipital headache, pain radiating to the neck, behavioral disturbances, altered mental status, decreased visual acuity, cortical blindness, homonymous hemianopia, generalized tonic − clonic seizures, status epilepticus, and focal neurologic deficits.^[2] Since its first description, it has been recognized in multiple different settings such as labile hypertension, hypertensive emergencies, preeclampsia, eclampsia, cerebrospinal fluid (CSF) leak and CSF hypotension, renal disease, SLE, sepsis, and cytotoxic drugs such as chemotherapy or immunosuppressive drug therapy. It tends to occur most often in the posterior circulation-parieto-occipital lobes and cerebellum and is associated with classic imaging findings. Prognosis is generally good, with reversal of symptoms within hours to days and imaging lesions within weeks to months. Multiple theories with potential mutual interaction have been proposed to explain the pathogenesis of PRES. A recent review summarized PRES arising in the setting of CSF leak.^[3]

PRES can manifest secondary to spinal procedures and pathologies. We attempt to systematically review the various spinal pathologies and interventions which have been attributed to cause PRES primarily from an etiologic point of view.

METHODOLOGY

Search strategy

A systematic search was performed in accordance with the PRISMA guidelines with the following search strategy:

Search phrase

((posterior reversible encephalopathy syndrome [MeSH Terms]) OR (reversible posterior leukoencephalopathy[MeSH Terms]) OR (acute hypertensive encephalopathy[MeSH Terms])) AND ((spine surgeries[MeSH Terms]) OR OR (spine surgery[MeSH Terms]) OR (spinal surgery[MeSH Terms]) OR (spinal intervention[MeSH Terms]) OR (spine intervention[MeSH Terms]) OR (spine operation[MeSH Terms]) OR (spinal operation[MeSH Terms]) OR (dural[MeSH Terms]) OR (thecoperitoneal shunt[MeSH Terma]) OR (Lumboperitoneal shunt[MeSH Terms]) OR (shunt[MeSH Terms]) OR (epidural[MeSH Terms]))

Database

Medline.

Timeline

Till August 2022.

Study eligibility

English language case reports and case series were included without geographic or temporal preference. Letters, experimental or translational studies, and reviews and reports where PRES were attributed to pregnancy-related causes were excluded. Study eligibility was assessed by two independent observers (AK and AGK) and disagreements were resolved with the opinion of a third independent observer (RS).

RESULTS

Literature search

Literature search yielded 16 studies, 56 additional studies were identified from the references of studies found. Fifteen duplicate studies were removed, the remaining 57 studies were screened through the title/abstract of study/availability of full text; 52 relevant studies were selected. Out of these, 44 were included for qualitative summarization [Table 1].

Table 1: PRISMA diagram summarizing search strategy and results

Study characteristics

Studies have been subdivided based on etiology attributed to PRES; data pertaining to primary outcomes are accordingly summarized in Tables 2 and 3.

Table 2: Table of studies reporting posterior reversible encephalopathy syndrome secondary to cerebrospinal fluid leaks after spinal interventions or pathologies

Table 3: Table of studies reporting posterior reversible encephalopathy syndrome secondary to autonomic dysreflexia/endothelial dysfunction after spinal interventions or pathologies

NARRATIVE REVIEW

PRES is called so because it tends to affect the posterior circulation more often and portends a good clinical prognosis with high chances of recovery and reversibility. The findings on imaging include hypodense areas on noncontrast computed tomography (CT) brain, hyperintense lesions in the bilateral pareto-occipital cortices, subcortical white matter, cerebellum on T2 weighted and FLAIR MR imaging, hyperintense lesions on apparent diffusion-coefficient mapping suggesting edema, foci of diffusion restriction may be seen in areas with ischemia. Tc99m single-photon emission CT scans when performed may demonstrate hyperperfusion correlating with the affected areas on the magnetic resonance imaging (MRI) scans.^[47] Preferential affliction of vessels of the posterior circulation could possibly be due to less sympathetic innervation and degree of autonomic control as compared to vessels in the anterior circulation.^[2] To our knowledge, ours is the first systematic review of the literature dealing with PRES specifically after or as a result of a spinal procedure, pathology, or trauma. The various spinal etiologies have been grouped and reviewed according to proposed mutually contributing pathogeneses in three categories - CSF hypotension, autonomic dysreflexia (AD) and resultant intermittent hypertension, and endothelial dysfunction.

Cerebrospinal fluid hypotension

According to the Monroe-Kellie doctrine, patients with low CSF pressures resulting from CSF leaks can develop vasogenic edema due a high pressure gradient between the hydrostatic pressure in the cerebral vasculature and intracranial pressure.^[3] Intracranial hypotension leads to cerebral vasodilation, predominantly of the veins causing a compensatory increase in cerebral blood volume.^[48] This alone could be sufficient to cause PRES but when combined with endothelial dysfunction or systemic hypertension can synergistically exacerbate existing dysfunction. Delayed compensatory cerebral autoregulation leading to vasoconstriction in response to the hyperperfusion can exacerbate PRES by causing hypoperfusion and resultant cytotoxic edema. An additional contributory mechanism could be due to intracranial hypotension causing “sagging of the brain.” This is evident on MR imaging as downward displacement of the brain, subdural fluid collections, distention of cerebral and spinal venous systems. This “brain sag” places traction on the meningeal vessels, leading to cerebral vasospasm, ischemia, and edema. The meningeal vessels appear hyperintense on MRI described as meningeal enhancement.^[11,15]

Delgado et al. report PRES in an elderly hypertensive patient which presented as seizures during extubation following L4-L5 laminectomy and dural sac decompression for degenerative spondylolisthesis. The authors theorize that an unrecognized CSF leak caused by dural dehiscence and exacerbated by drain placement during repositioning from prone to supine as evidenced by pseudomeningocoele and root migration toward dura on follow-up MRI could have been the initial insult and this was exacerbated by hypertension. The patient also had nonconvulsive status epilepticus on electroencephalography, recovered fully with blood pressure control and conservative measures.^[5] A case of PRES and focal subarachnoid hemorrhage postlumboperitoneal shunt (LPS) was reported by Fok et al. in a normotensive young adult. The patient had severe visual deterioration and headache which improved upon insertion of a programmable ventriculoperitoneal shunt (VPS) and removal of the LPS. The programmable VPS could better control CSF egress and avoid precipitous lowering of CSF pressure.^[6] Grelat et al. report PRES in a case of a normotensive elderly patient with chronic hydrocephalus postdepletive lumbar puncture. The patient had cortical blindness and hemiplegia which was conservatively managed. The patient later underwent a VPS and redeveloped PRES, for which the shunt chamber pressure was set higher.^[7] A similar case was reported by Karakis et al. in a young adult with cryptococcal meningitis secondary to human immunodeficiency virus infection with PRES post-LPS which resolved after a programmable VPS was inserted. Intracranial hypotension due to CSF drainage combined with an inflammatory mileu might have precipitated PRES in this scenario.^[8]

Shields et al. reported PRES occurring in a patient with controlled hypertension post T4-5 discectomy due to inadvertent intraoperative CSF leak. A lumbar drain was placed to assist in leak healing which could have precipitated PRES further. Re-exploration with repair of the CSF leak along the left T5 nerve root led to the resolution of symptoms.^[9] A similar case was reported by Hammad et al. where a lumbar drain and epidural blood patch were used to manage dural tear complicating lumbosacral instrumentation in an elderly hypertensive for chronic back pain. Lumbar drainage although effective for CSF leak management by providing another avenue for CSF egress and inducing intracranial hypotension exacerbated PRES in both cases.^[10] Santillan et al. report PRES occurring in an elderly normotensive patient with spontaneous lumbar CSF leak, it was managed with an epidural blood patch.^[11] Yamada et al. report a case of a middle-aged hypertensive patient receiving epidural analgesia for cholecystectomy developing PRES associated with cerebral vasoconstriction which was managed with volume expanding agents. This case highlights the potential dual pathogenesis of PRES namely hyperperfusion followed by deranged overcompensatory autoregulation causing cerebral hypoperfusion.^[12] Ortiz et al. present the case of a young adult female with multiple sclerosis (MS) who developed PRES following treatment of postdural puncture headache (PDPS) with intravenous caffeine. The authors surmise that the increased vascular permeability due to MS combined with cerebral vasoconstriction due to caffeine could have resulted in localized patches of hyperperfusion and vasogenic edema combined with hypoperfusion due to vasoconstriction.^[13] The case reported by Eran et al. developed PRES after undergoing combined general and spinal anesthesia for video-assisted pulmonary wedge resection. The patient was middle aged and normotensive, the authors attributing PRES to the intrathecal morphine usage.^[14]

Ho et al. report a case of PRES like clinical and imaging findings in a primipara patient 2 days postdelivery after subsidence of PDPS. The patient had imaging findings of PRES combined with bilateral diffuse vasospasm and normotension, the patient recovered after intravenous magnesium sulphate was administered. The authors proposed CSF leak postdural puncture for spinal block could cause brain sagging and stretch on cerebral vessels precipitating vasospasm.^[15] A similar case was reported by Sagir et al.^[16] Zheng et al. present a case of PRES in a postpartum patient which the authors attributed to inadvertent dural puncture in the course of epidural anesthesia combined with hypertension, imaging showed signs of vasospasm along with classic findings of PRES. The authors theorized that CSF hypotension combined with systemic hypertension led to massive delayed overcompensating vasospasm. Management of the CSF leak and control of hypertension are paramount.^[3] A similar case was reported by Doherty et al. with dural puncture during epidural analgesia for a cesarean section;^[17] Hong et al.^[18] also reported a case with normotension being managed with magnesium sulphate similar to Yildiz et al.^[19] Pugliese et al. reported a similar case which was managed with epidural blood patch.^[20] Magnesium sulfate was also used by Rajan et al.^[21] to manage PRES postspinal anesthesia for caesarean section while Feil et al.^[22] reported a case of PRES with reversible cerebral vasoconstriction syndrome secondary to CSF leak resulting from epidural analgesia which was managed with blood patch. Prout et al. present PRES occurring postpartum in a patient with transient hypertension which was worsened due to chest pain secondary to severe cough resulting from a respiratory tract infection; there were no clinical or biochemical signs of meningitis.^[23] The case reported by Orehek et al. developed tonsillar herniation and midbrain sagging secondary to a suspected CSF leak and intracranial hypotension postepidural analgesia for cesarean section, this case was also managed with epidural blood patch.^[24] In a similar setting, PRES was reported in a postpartum patient with pneumoventricle and hypertension during the onset of PRES by Torrillo et al.^[4] Oxford et al. report PRES occurring postremoval of lumbar drain inserted in an elderly controlled hypertensive patient postendoscopic endonasal resection of a sellar mass. PRES resolved with conservative management and the authors theorize that continued CSF leak from the lumbar drain-induced durotomy combined with intermittent hypertension could result in PRES. Chronic hypertension could predispose to overcompensation of cerebral hyperperfusion with vasospasm and resultant hypoperfusion.^[25] PRES was reported in an elderly hypertensive following inadvertent dural puncture during epidural analgesia for laparotomy by Shah et al.^[26] Hypertension combined with CSF leak was proposed as the cause of PRES. Pradhan et al. report PRES in a young adult undergoing live related renal transplant and attributed it to CSF leak due to subarachnoid migration of epidural analgesia catheter combined with endothelial dysfunction and vasospasm secondary to immunosuppressants, especially cyclosporin. The authors concluded that CSF leak alone is unlikely to lead to PRES but rather will result in PDPS, PRES might result from a combination of intracranial hypotension and resultant hyperperfusion with disordered autoregulation.^[27]

Autonomic dysreflexia

Cerebral autoregulation generally has two components - myogenic and neurogenic. Sudden fluctuations in blood pressure tend to overwhelm the myogenic component making neurogenic autoregulation the sole mechanism left.^[49] Due to sparse innervation of the posterior cerebral (?) circulation, it is thought to be more predisposed to development of hyperperfusion with vasogenic edema which can be compounded by overcompensatory hypoperfusion leading to PRES.^[50] AD postspinal intervention or more frequently postspinal trauma results from disruption of supraspinal inhibitory signals to spinal vasomotor centers which causes massive activation and autonomic surge triggered by any noxious stimulus such as urinary tract infection (UTI) originating from more inferior levels reaching the spinal level in question. This is more likely to be seen with upper dorsal and cervical spinal cord disruptions and interventions.^[51] In spinal trauma, disruption of the intermediolateral column causes a decreased sympathetic drive resulting in a low baseline blood pressure.^[52] In such patients, sudden increases of blood pressure, triggered by AD, to levels considered normal for healthy individuals may overwhelm autoregulation and precipitate PRES.^[29]

Gopalakrishna et al. report PRES occurring in an adolescent with upper dorsal spinal hemangioma who developed postoperative epidural hematoma. The patient had fluctuations in blood pressure during the second perioperative period postepidural hematoma evacuation. The authors surmised PRES was the result of AD due to the dorsal epidural hematoma.^[28] Hubbard et al. present two cases with old upper dorsal or cervical complete spinal cord injuries (SCI) with UTI who present with AD and widely fluctuating blood pressures who developed PRES. Tight blood pressure control and monitoring resulted in complete recovery of PRES-related symptoms.^[29] The cases presented by Phillips and Krassioukov,^[30] Squair et al.^[32] and Matias et al.^[31] also had complete SCI and AD secondary to UTI. The etiology of AD can vary with the cases reported by Chaves and Lee,^[33] Joa et al.^[34] and Yamashita et al.^[35] developing AD due to assisted cough maneuvres, urinary retention, and urethral injury during catheter change. Farooq et al. report a case of complete SCI with open infected abdominal wounds and UTI; AD was the result of the UTI and PRES was attributed to the combination of the endotoxic septic milieu which might accentuate cerebral vascular permeability and AD.^[36] All of the above-mentioned cases had high thoracic or cervical SCI. Yi et al. report a case of an elderly hypertensive patient undergoing lumbar instrumentation without CSF leak but perioperative hypertension which could have overwhelmed cerebral autoregulation and resulted in PRES.^[37] Sanpei et al. report a case of an elderly rheumatoid arthritis (RA) patient with history of chronic intake of cytotoxic drugs who developed Guillain-Barré syndrome (GBS) postsurgery for lumbar canal stenosis. The resultant AD from GBS combined with probable endothelial dysfunction due to longstanding inflammatory milieu as a result of RA and cytotoxic drug intake was theorized to precipitate PRES.^[38] Zimering and Mesfin report a similar case in an elderly patient with RA who underwent anterior approach for decompression and fixation for cervical subluxation, although the patient was hypertensive and did not develop GBS.^[39] Whiting et al. report three cases in elderly or middle aged patients with thoracic or cervical intervention resulting from cord injury during spinal cord stimulation, thoracic disc, or cervical kyphotic deformity. All patients had iatrogenically elevated BP to improve spinal cord perfusion which was theorized to result in PRES.^[40] El Rachkidi et al. present PRES occurring in a young adult with traumatic blunt carotid dissection without brain injury.^[41] The authors propose PRES was the result of impaired baroregulation due to cervical carotid dissection.

Endothelial dysfunction

PRES results from overwhelming of the cerebral autoregulation with the threshold of decompensation being possibly lowered as a result of cerebral vascular endothelial dysfunction resulting from the presence of intradural blood or cytotoxic drugs. This might result in vasogenic edema appearing earlier and at a higher magnitude.^[53]

Porter and Schmitz report a case of an elderly hypertensive patient who had cervical and lumbar canal stenosis who was operated initially for the lumbar disease and had undergone epidural steroid injections. In the perioperative period for the cervical disease, the patient had an episode of transient hypertension and developed PRES. The authors theorized lower threshold of developing PRES as a result of endothelial dysfunction resulting from steroid injections.^[42] A similar case was reported in an elderly normotensive patient who had undergone transforaminal epidural steroid injections by Kim et al.^[43] Vakharia et al. report PRES occurring in an elderly normotensive patient who had undergone nephrectomy for renal cell carcinoma without adjuvant chemo or radiotherapy and presented with a lower thoracic vertebral body metastasis. The patient initially underwent embolization followed by high dose systemic steroid therapy for the same followed by surgical excision. PRES was attributed to the high dose steroid regimen causing endothelial dysfunction.^[44] Valone et al. report PRES in an elderly normotensive patient with prior lacunar infarct who underwent three-staged correction of thoracolumbar deformity. The authors propose PRES occurring due to the previous infarct making autoregulation more susceptible to the transient hypertensive episodes which maybe due to thoracic cord stimulation as a result of deformity correction.^[45] Chen et al. present PRES occurring in a young adult with a history of minor neck injury resulting in a cervicothoracic spinal subdural hematoma. The patient also had cerebral vasoconstriction; the authors propose the presence of subdural blood might have precipitated cerebral vasoconstriction and spinal location might have led to impaired baroregulation and transient AD, although blood pressure fluctuations were minor.^[46]

CONCLUSIONS

PRES as a pathologic entity has multifactorial pathogenic mechanisms. It can be summarized to result primarily from an event of hyperperfusion that overwhelms cerebral autoregulatory mechanisms with predisposition to posterior circulation as a result of sparse autonomic innervation. This results in vasogenic edema and compensatory autoregulation. This might compound with overcompensatory regulation or endothelial dysfunction that results in cerebral vasoconstriction with endothelial dysfunction having an additional effect of increased cerebral vascular permeability worsening the edema.

Spinal pathologies and interventions can contribute in a multitude of ways to these pathogenic mechanisms and PRES remains a rare but important underrecognized reason for morbidity following spinal interventions. Fortunately, in the majority of cases, it is reversible.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.