- Email: [email protected]
Unusual Delayed Presentation of Posterior Reversible Encephalopathy Syndrome Following Vestibular Schwannoma Surgery: A Rare Neurologic Emergency
Accepted Manuscript Unusual delayed presentation of PRES following vestibular schwannoma surgery: a rare neurological emergency Deepak Khatri, MS, MCh, Kamlesh singh bhaisora, Mch, Abhijit parab, MS, Arun K. srivastava, MCh, Kuntal Kanti, Das, Mch PII:
S1878-8750(18)32130-2
DOI:
10.1016/j.wneu.2018.09.084
Reference:
WNEU 10289
To appear in:
World Neurosurgery
Received Date: 4 June 2018 Revised Date:
7 September 2018
Accepted Date: 11 September 2018
Please cite this article as: Khatri D, bhaisora Ks, parab A, srivastava AK, Kanti K, Unusual delayed presentation of PRES following vestibular schwannoma surgery: a rare neurological emergency, World Neurosurgery (2018), doi: https://doi.org/10.1016/j.wneu.2018.09.084. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Manuscript type: Case report Title: Unusual delayed presentation of PRES following vestibular schwannoma surgery: a rare neurological emergency
First Author: Deepak Khatri, MS, MCh
RI PT
Name of authors:
1. Deepak Khatri, MS, MCh Post-doctoral fellow, Neurosurgery, SGPGIMS [email protected]
M AN U
2. Kamlesh singh bhaisora, Mch Assistant Professor, Neurosurgery, SGPGIMS [email protected]
SC
Order of Authors: Deepak khatri, MS,MCh; Kamlesh singh bhaisora, Mch; Abhijit parab, MS; Arun kumar srivastava, MCh; Kuntal Kanti Das, Mch
3. Abhijit parab, MS Resident, Neurosurgery, SGPGIMS [email protected]
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4. Arun K srivastava, MCh Additional Professor, Neurosurgery, SGPGIMS [email protected]
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EP
5. Kuntal Kanti Das, Mch Assistant Professor, Neurosurgery, SGPGIMS [email protected]
Corresponding author: Kamlesh singh bhaisora Postal Address: Department of Neurosurgery, SGPGIMS, Raibareily road, Lucknow, Uttar Pradesh, ZIP – 226014 Running title: Unusual delayed presentation of PRES following vestibular schwannoma surgery
ACCEPTED MANUSCRIPT
Unusual delayed presentation of PRES following vestibular schwannoma surgery: a rare neurological emergency
RI PT
Introduction In 1996, Hinchey et al first described posterior reversible encephalopathy syndrome (PRES) as a rare clinical condition in which patient presents with heterogeneous clinical findings
SC
such as altered mental condition, seizure, vision loss and vomiting along with characteristic radiological changes on MRI (T2 and FLAIR sequences). [1] Radiologically, patient usually
M AN U
have diffuse subcortical vasogenic edema, most commonly in the parieto- occipital regions, but it may involve frontal region, cerebellum and parts of brainstem in severe cases. PRES has been reported to be associated with various conditions like hypertension, eclampsia, sepsis, electrolyte imbalances, autoimmune diseases and immunosuppressive therapy. [2,3] It
TE D
is a self-limiting condition with good outcome with aggressive management with antihypertensive therapy and antiepileptic drugs. On very rare occasions, PRES has been found associated with posterior fossa tumor and
EP
lateral skull base surgery. [2-9] Wide intra-operative BP fluctuations and surgical manipulation of the rostral ventro-lateral medulla (RVLM) have been the frequently proposed
AC C
culprits. However, exact pathophysiology of PRES still remains a controversy. So far, only 10 cases of various posterior fossa tumors including only one case of vestibular schwannoma developing features of PRES intra-operatively or in immediate post-operative period have been reported. [2-9] All previously reported cases presented within a week of tumor surgery. We are reporting the very first case of “unusually delayed” clinical presentation of this rare condition 8 months after vestibular schwannoma surgery in a young female along with review of pertinent literature.
ACCEPTED MANUSCRIPT
Case history
A 23 years old female patient previously operated for right vestibular schwannoma presented
RI PT
in our emergency department (ED) with altered sensorium, seizures for 6-7 days. Patient had multiple episodes (about 12-15) of generalized tonic-clonic seizures on the day of admission itself.
SC
Eight months back, she underwent retromastoid sub-occipital craniectomy and gross total excision of right vestibular schwannoma uneventfully. [Figure 1] However, she required a
M AN U
medium pressure ventriculo-peritoneal shunt on post-operative day (POD) 4 for unresolved hydrocephalus. Patient was then discharged with uneventful recovery until 2 months later when she developed recurrence of lower cranial nerve and cerebellar symptoms. Repeat contrast MRI showed recurrence of the tumor, therefore patient was planned for re-surgery.
TE D
[Figure 1]
On examination, she had eye opening to pain, incomprehensible verbal response and localizing to painful stimuli. At the time of presentation in ED, her blood pressure was
EP
recorded (180/110 mmHg) high! Emergency CT head showed diffuse subcortical edema
AC C
involving bilateral frontal, and parieto-occipital lobes without any significant increase in tumor size as compared to the post-operative scan. Also, no compression of fourth ventricle or hydrocephalus was noted. At this point, possibility of cortical venous thrombosis and acute demyelinating encephalitis were considered among differentials and a contrast MRI with MR venography was planned. Upon MRI imaging, bilateral frontal and parieto-occipital lobes were found to have diffuse subcortical edema with evidence of micro bleeds on SWAN sequences. A large recurrence of the tumor along with increase in cystic component was also noted in right cerebello-pontine angle cistern. Peri-lesional edema was seen involving middle
ACCEPTED MANUSCRIPT cerebral peduncle causing mass effect on pons and medulla with mild effacement of 4th ventricle. Ventricular tip of shunt was seen in the frontal horn without any hydrocephalus. MR venography did not reveal any signs of thrombosis of cortical veins or deep venous sinuses. [Figure 2] There was no history of chronic hypertension, autoimmune disease,
RI PT
immunosuppressive therapy, intake of vasoactive drugs, CSF leak from wound or pregnancy. Electrolyte imbalances, meningitis and sepsis were also ruled out. Abdominal ultrasonogram revealed normal caliber of renal arteries bilaterally.
SC
Having excluded other common possibilities, radiological findings of bilateral diffuse subcortical edema and microbleeds with altered sensorium and seizures in an operated case of
M AN U
vestibular schwannoma lead us to think of posterior reversible encephalopathy syndrome in our patient. Along with above-mentioned clinical presentation, the finding of high blood pressure did corroborate our diagnosis.
Patient was managed conservatively with anti-epileptics and antihypertensive therapy was
TE D
started. During 2-week hospital course, she regained consciousness, was able to follow commands with no new-onset neurological deficits. Patient was discharged with plan for
Discussion
EP
excision of recurrent tumor.
AC C
Posterior reversible encephalopathy syndrome is a distinct clinico-radiological entity, very rarely encountered in neurosurgical practice. Various clinical findings have been described to be associated with this syndrome but it often presents as a global encephalopathy. Seizures, headache and altered sensorium along with visual deficits are the most frequently reported symptoms. Currently available literature suggests PRES to be associated with pregnancy, cytotoxic drugs like cisplatin, cyclosporine, tacrolimus etc; viral or bacterial infection, trauma and vasospasm therapy among others. Recently, few cases of posterior fossa tumor associated with PRES have been described. [2-9] Most of these tumors were around 4th ventricle, with
ACCEPTED MANUSCRIPT only one case of vestibular schwannoma. Details of these cases have been summarized in table 1. Several authors have attempted to explain the pathophysiological mechanism for development of PRES which includes – surgical manipulation of RVLM, jugular bulb
cushing’s
reflex
secondary to
obstructive
RI PT
occlusion, raised venous pressure, production of vasoactive neuropeptides, a result of hydrocephalus.
[2-9]
However,
exact
pathophysiology of PRES in neurosurgical cases still remains elusive due to their rarity.
SC
Moriarity et al have proposed that development of PRES in posterior fossa tumor surgery may be explained as a result of uncontrolled intra-operative variation in blood pressure,
M AN U
which causes loss of auto regulatory response of cerebral vasculature leading damage to blood-brain barrier (BBB). [2] This hypertensive disruption of BBB causes extravasation of plasma and macromolecules leading to vasogenic edema and microbleeds. Posterior circulation is more prone to autonomic dysreflexia because of its meagre sympathetic
TE D
innervation.
Although hypertension thought to be initiating cause of PRES, mean arterial pressure in most hypertensive PRES patients stays within normal autoregulatory response limits. [10]
EP
Interestingly, the degree of vasogenic edema as well did not co-relate with severity blood
AC C
pressure. [11] Of note, PRES has also been reported in patients with normal BP. [12] Bartynski et al believe that a complex systemic inflammatory response involving activation of T-cells and certain inflammatory cytokines leading to systemic vasoconstriction and hypoperfusion may be the underlying mechanism in such normotensive-PRES cases. [13] Few authors have proposed that left-sided tumors are more prone to result in PRES postoperatively. [8] However, our case suggests that laterality of the tumor plays no role in development of PRES following surgery. Also, it is interesting to note that majority (9 out of
ACCEPTED MANUSCRIPT 10) of the previously reported cases are males. So, male gender predilection in this rare condition still needs to be investigated. Sorour et al have described ‘delayed’ onset of PRES on POD 8 of vestibular schwannoma surgery. [8] To our knowledge, an ‘unusually prolonged delay’ months after the surgery has
RI PT
never been reported earlier. A high index of clinical suspicion and low threshold for radiological investigation helped us clinch the diagnosis in our case.
Even though several pathophysiological mechanisms have been proposed earlier, none of
SC
them fully explain the development of PRES in our case. We believe that rapid recurrence of the residual tumor leading to brainstem distortion may have lead to such findings in our
histopathological diagnosis. [Figure 3]
M AN U
patient. Such an unusual presentation in a vestibular schwannoma even made us review our
Hedna et al have established that PRES is associated with brain hypoperfusion based upon CT perfusion studies and may even mimic stroke!! [14] Therefore, it becomes imperative to
TE D
identify promptly and aggressive management of this frequently reversible condition to avoid subsequent neurological sequalae.
To conclude, PRES should be considered among possible complications of posterior fossa
EP
tumor surgery which presents with acute neurological symptoms. With correct diagnosis in
AC C
time and aggressive treatment, most patients achieve complete neurological recovery within 1-3 months and clinical improvement often precedes resolution of lesions radiologically.
References
1. Hinchey J,
Chaves
C,
Appignani
B,
et
al.
A
reversible
posterior
leukoencephalopathy syndrome. N Engl J Med 1996;334(8): 494–500. 2. Moriarity JL Jr, Lim M, Storm PB, Beauchamp NJ Jr, Olivi A. Reversible
ACCEPTED MANUSCRIPT posterior leukoencephalopathy occurring during resection of a posterior fossa tumor: case report and review of the literature. Neurosurgery 2001;49(5):1237– 1239; discussion 1239–1240. 3. Patel AJ, Fox BD, Fulkerson DH, et al. Posterior reversible encephalopathy
RI PT
syndrome during posterior fossa tumor resection in a child. J Neurosurg Pediatr 2010;6(4):377–380.
4. Gephart MG, Taft BP, Giese AK, Guzman R, Edwards MS. Perioperative
SC
posterior reversible encephalopathy syndrome in 2 pediatric neurosurgery patients
M AN U
with brainstem ependymoma. J Neurosurg Pediatr 2011;7(3):235–237. 5. Sánchez-cuadrado LL, Royo A, Cerdeño V, Roda JM, Gavilán J. Reversible posterior leukoencephalopathy syndrome after lateral skull base surgery. Otol Neurotol 2011;32(5):838–840.
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6. Avecillas-Chasín JM, Gómez G, Jorquera M, Alvarado LR, Barcia JA. Delayed posterior reversible encephalopathy syndrome (PRES) after posterior fossa surgery. Acta Neurochir (Wien) 2013; 155(6):1045–1047.
EP
7. Kuhnt D, Becker A, Benes L, Nimsky C. Reversible cortical blindness and
AC C
internuclear ophthalmoplegia after neurosurgical operation: case report and review of the literature. J Neurol Surg A Cent Eur Neurosurg 2013;74(Suppl 1):e128–e132.
8. Sorour M, Sayama C, Couldwell WT. Posterior Reversible Encephalopathy Syndrome after Surgical Resection of a Giant Vestibular Schwannoma: Case Report and Literature Review. J Neurol Surg A Cent Eur Neurosurg. 2016 May;77(3):274-9.
ACCEPTED MANUSCRIPT 9. González Quarante LH, Mena-Bernal JH, Martín BP, Ramírez Carrasco M, Muñoz Casado MJ, Martínez de Aragón A, de las Heras RS. Posterior reversible encephalopathy syndrome (PRES): a rare condition after resection of posterior fossa tumors: two new cases and review of the literature. Childs Nerv Syst. 2016
RI PT
May;32(5):857-63.
10. Bartynski WS, Boardman JF. Catheter angiography, MR angiography, and MR
Neuroradiol 2008;29(3):447–455.
SC
perfusion in posterior reversible encephalopathy syndrome. AJNR Am J
M AN U
11. Bartynski WS, Boardman JF, Zeigler ZR, Shadduck RK, Lister J. Posterior reversible encephalopathy syndrome in infection, sepsis, and shock. AJNR Am J Neuroradiol 2006;27(10):2179–2190.
12. Vakharia K, Siasios I, Dimopoulos VG, Pollina J. Posterior Reversible
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Encephalopathy Syndrome Resolving Within 48 Hours in a Normotensive Patient Who Underwent Thoracic Spine Surgery. Journal of Clinical Medicine Research. 2016;8(3):263-266. WS.
Posterior
EP
13. Bartynski
reversible
encephalopathy
syndrome,
part
2:
AC C
controversies surrounding pathophysiology of vasogenic edema. AJNR Am J Neuroradiol 2008;29(6):1043–1049.
14. Hedna VS, Stead LG, Bidari S, et al. Posterior reversible encephalopathy syndrome (PRES) and CT perfusion changes. International Journal of Emergency Medicine 2012;5:12.
ACCEPTED MANUSCRIPT
4th ventricle ependymoma
Day of onset Day of surgery
Radiological involvement Parieto-occipital
Recovery period 2 months
Moriarity et al. 2001 [2]
19/Male
Patel et al. 2010 [3] 6/Male
Cerebellar juvenile pilocytic astrocytoma
Day of surgery
Parieto-occipital, Temporal cortex
3 months
Gephart et al. 2011 [4]
4/Male
4th ventricle grade III ependymoma
Day 7
7/Male
4th ventricle grade II ependymoma
Day 5
Parieto-occipital with speckled contrast enhancement Holohemispheric and cerebellar
58/Male
Day 4 Adenoid cystic carcinoma (right external auditory canal with intracranial extension)
Sanchez-Cuadrado et al. 2011 [5]
RI PT
Histo-pathology
SC
Age/sex
Occipital, cerebellar
M AN U
Study
3 months
1 month 2 weeks
Not reported. 4th ventricular tumor
Day 8
Parieto-occipital, Basal ganglia
Kuhnt et al. 2013 [7]
63/Male
Two infratentorial hemangiopericytomas
Day of surgery
Parieto-occipital, 1 week Rostral paramedian mesencephalon and pons
Sorour et al. 2013 [8]
57/Female Giant acoustic schwannoma
Day 2
Parieto-occipital
1 month
Quarante et al. 2015 [9]
4/Male
Day 9
Parieto-occipital
1 month
Day 2
Diffusely involving both hemispheres Diffusely involving both hemispheres
1 month
EP
TE D
Avecillas-Chasín et 19/Male al. 2013 [6]
AC C 14/Male
Present case
Posterior fossa medulloblastoma Grade II ependymoma (fourth ventricle)
23/Female Acoustic schwannoma
8 months
1 month
2 weeks
Table 1: A summary of previously reported cases of PRES associated with various posterior fossa tumor surgeries.
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
Figure 1: Pre-operative MRI T1- & T2- weighted images (axial, coronal & saggital views) showing large solid-cystic vestibular schwannoma reaching causing mass effect on brainstem
EP
with proximal ventriculomegaly. [A-C] Immediate post-operative contrast CT head (axial
AC C
and saggital views) suggestive of gross total resection of the tumor with well-formed surgical cavity. [D, E] At 3 month follow-up, T2WI axial view MRI shows recurrence of tumor causing distortion of the brainstem. [F]
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
Figure 2: Non-contrast CT head done in emergency 8 months after surgery showing diffuse
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subcortical edema involving bilateral frontal, & parieto-occipital lobes with no ventriculomegaly. Ventricular shunt tip is also seen in the frontal horn. [A, B] Axial view T2WI MRI image showing increase in the size of recurrent tumor measuring about 5 x 4 cm
EP
along with enlargement of cystic component posteriorly as well as medially (Blue arrows) causing brainstem compression with mild effacement of 4th ventricle. [C] On T2-weighted
AC C
MRI image (axial view), bilateral frontal and parieto-occipital lobes were found to have diffuse subcortical edema with hyperintense area in left parieto-occipital region. [D] There was evidence of micro bleeds seen on SWAN sequence. [E] MR venography did not reveal any signs of thrombosis of cortical veins or deep venous sinuses. [F] MR angiogram (coronal and lateral views) showing normal vasculature in anterior as well as posterior circulation. [G, H]
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
Figure 3: Microphotograph of hematoxylin and eosin stained section showing tumor
EP
composed of spindle cells disposed in vaguely alternating cellular and hypocellular areas. Tumor cells showed oval to elongated nuclei, bland chromatin, inconspicuous nucleoli and
AC C
moderate amount of cytoplasm. Occasional verocay bodies, composed of palisaded nuclei and few blood vessels were noted in the stroma. There was no evidence of increased mitotic activity, necrosis or malignancy.
ACCEPTED MANUSCRIPT Highlights:
•
A rare clinical condition with uncertain pathophysiology in which patient presents
•
RI PT
with heterogeneous clinical findings.
Associated with various conditions like hypertension, eclampsia, sepsis, electrolyte
•
SC
imbalances, autoimmune diseases and immunosuppressive therapy.
So far, only 10 cases of various posterior fossa tumor surgery have presented with
•
M AN U
PRES intra-operatively or within a week of surgery.
We are reporting the very first case of “unusually delayed” clinical presentation of
Also, we have proposed “Rapid tumor recurrence leading to rostral medulla
EP
compression” as a new pathophysiological mechanism of this entity.
AC C
•
TE D
this rare condition 8 months after vestibular schwannoma surgery.
ACCEPTED MANUSCRIPT Abbreviations:
EP
TE D
M AN U
SC
RI PT
Posterior reversible encephalopathy syndrome – PRES Rostral ventro-lateral medulla – RVLM Emergency department – ED Post-operative day – POD Blood-brain barrier - BBB
AC C
• • • • •
S1878-8750(18)32130-2
DOI:
10.1016/j.wneu.2018.09.084
Reference:
WNEU 10289
To appear in:
World Neurosurgery
Received Date: 4 June 2018 Revised Date:
7 September 2018
Accepted Date: 11 September 2018
Please cite this article as: Khatri D, bhaisora Ks, parab A, srivastava AK, Kanti K, Unusual delayed presentation of PRES following vestibular schwannoma surgery: a rare neurological emergency, World Neurosurgery (2018), doi: https://doi.org/10.1016/j.wneu.2018.09.084. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Manuscript type: Case report Title: Unusual delayed presentation of PRES following vestibular schwannoma surgery: a rare neurological emergency
First Author: Deepak Khatri, MS, MCh
RI PT
Name of authors:
1. Deepak Khatri, MS, MCh Post-doctoral fellow, Neurosurgery, SGPGIMS [email protected]
M AN U
2. Kamlesh singh bhaisora, Mch Assistant Professor, Neurosurgery, SGPGIMS [email protected]
SC
Order of Authors: Deepak khatri, MS,MCh; Kamlesh singh bhaisora, Mch; Abhijit parab, MS; Arun kumar srivastava, MCh; Kuntal Kanti Das, Mch
3. Abhijit parab, MS Resident, Neurosurgery, SGPGIMS [email protected]
TE D
4. Arun K srivastava, MCh Additional Professor, Neurosurgery, SGPGIMS [email protected]
AC C
EP
5. Kuntal Kanti Das, Mch Assistant Professor, Neurosurgery, SGPGIMS [email protected]
Corresponding author: Kamlesh singh bhaisora Postal Address: Department of Neurosurgery, SGPGIMS, Raibareily road, Lucknow, Uttar Pradesh, ZIP – 226014 Running title: Unusual delayed presentation of PRES following vestibular schwannoma surgery
ACCEPTED MANUSCRIPT
Unusual delayed presentation of PRES following vestibular schwannoma surgery: a rare neurological emergency
RI PT
Introduction In 1996, Hinchey et al first described posterior reversible encephalopathy syndrome (PRES) as a rare clinical condition in which patient presents with heterogeneous clinical findings
SC
such as altered mental condition, seizure, vision loss and vomiting along with characteristic radiological changes on MRI (T2 and FLAIR sequences). [1] Radiologically, patient usually
M AN U
have diffuse subcortical vasogenic edema, most commonly in the parieto- occipital regions, but it may involve frontal region, cerebellum and parts of brainstem in severe cases. PRES has been reported to be associated with various conditions like hypertension, eclampsia, sepsis, electrolyte imbalances, autoimmune diseases and immunosuppressive therapy. [2,3] It
TE D
is a self-limiting condition with good outcome with aggressive management with antihypertensive therapy and antiepileptic drugs. On very rare occasions, PRES has been found associated with posterior fossa tumor and
EP
lateral skull base surgery. [2-9] Wide intra-operative BP fluctuations and surgical manipulation of the rostral ventro-lateral medulla (RVLM) have been the frequently proposed
AC C
culprits. However, exact pathophysiology of PRES still remains a controversy. So far, only 10 cases of various posterior fossa tumors including only one case of vestibular schwannoma developing features of PRES intra-operatively or in immediate post-operative period have been reported. [2-9] All previously reported cases presented within a week of tumor surgery. We are reporting the very first case of “unusually delayed” clinical presentation of this rare condition 8 months after vestibular schwannoma surgery in a young female along with review of pertinent literature.
ACCEPTED MANUSCRIPT
Case history
A 23 years old female patient previously operated for right vestibular schwannoma presented
RI PT
in our emergency department (ED) with altered sensorium, seizures for 6-7 days. Patient had multiple episodes (about 12-15) of generalized tonic-clonic seizures on the day of admission itself.
SC
Eight months back, she underwent retromastoid sub-occipital craniectomy and gross total excision of right vestibular schwannoma uneventfully. [Figure 1] However, she required a
M AN U
medium pressure ventriculo-peritoneal shunt on post-operative day (POD) 4 for unresolved hydrocephalus. Patient was then discharged with uneventful recovery until 2 months later when she developed recurrence of lower cranial nerve and cerebellar symptoms. Repeat contrast MRI showed recurrence of the tumor, therefore patient was planned for re-surgery.
TE D
[Figure 1]
On examination, she had eye opening to pain, incomprehensible verbal response and localizing to painful stimuli. At the time of presentation in ED, her blood pressure was
EP
recorded (180/110 mmHg) high! Emergency CT head showed diffuse subcortical edema
AC C
involving bilateral frontal, and parieto-occipital lobes without any significant increase in tumor size as compared to the post-operative scan. Also, no compression of fourth ventricle or hydrocephalus was noted. At this point, possibility of cortical venous thrombosis and acute demyelinating encephalitis were considered among differentials and a contrast MRI with MR venography was planned. Upon MRI imaging, bilateral frontal and parieto-occipital lobes were found to have diffuse subcortical edema with evidence of micro bleeds on SWAN sequences. A large recurrence of the tumor along with increase in cystic component was also noted in right cerebello-pontine angle cistern. Peri-lesional edema was seen involving middle
ACCEPTED MANUSCRIPT cerebral peduncle causing mass effect on pons and medulla with mild effacement of 4th ventricle. Ventricular tip of shunt was seen in the frontal horn without any hydrocephalus. MR venography did not reveal any signs of thrombosis of cortical veins or deep venous sinuses. [Figure 2] There was no history of chronic hypertension, autoimmune disease,
RI PT
immunosuppressive therapy, intake of vasoactive drugs, CSF leak from wound or pregnancy. Electrolyte imbalances, meningitis and sepsis were also ruled out. Abdominal ultrasonogram revealed normal caliber of renal arteries bilaterally.
SC
Having excluded other common possibilities, radiological findings of bilateral diffuse subcortical edema and microbleeds with altered sensorium and seizures in an operated case of
M AN U
vestibular schwannoma lead us to think of posterior reversible encephalopathy syndrome in our patient. Along with above-mentioned clinical presentation, the finding of high blood pressure did corroborate our diagnosis.
Patient was managed conservatively with anti-epileptics and antihypertensive therapy was
TE D
started. During 2-week hospital course, she regained consciousness, was able to follow commands with no new-onset neurological deficits. Patient was discharged with plan for
Discussion
EP
excision of recurrent tumor.
AC C
Posterior reversible encephalopathy syndrome is a distinct clinico-radiological entity, very rarely encountered in neurosurgical practice. Various clinical findings have been described to be associated with this syndrome but it often presents as a global encephalopathy. Seizures, headache and altered sensorium along with visual deficits are the most frequently reported symptoms. Currently available literature suggests PRES to be associated with pregnancy, cytotoxic drugs like cisplatin, cyclosporine, tacrolimus etc; viral or bacterial infection, trauma and vasospasm therapy among others. Recently, few cases of posterior fossa tumor associated with PRES have been described. [2-9] Most of these tumors were around 4th ventricle, with
ACCEPTED MANUSCRIPT only one case of vestibular schwannoma. Details of these cases have been summarized in table 1. Several authors have attempted to explain the pathophysiological mechanism for development of PRES which includes – surgical manipulation of RVLM, jugular bulb
cushing’s
reflex
secondary to
obstructive
RI PT
occlusion, raised venous pressure, production of vasoactive neuropeptides, a result of hydrocephalus.
[2-9]
However,
exact
pathophysiology of PRES in neurosurgical cases still remains elusive due to their rarity.
SC
Moriarity et al have proposed that development of PRES in posterior fossa tumor surgery may be explained as a result of uncontrolled intra-operative variation in blood pressure,
M AN U
which causes loss of auto regulatory response of cerebral vasculature leading damage to blood-brain barrier (BBB). [2] This hypertensive disruption of BBB causes extravasation of plasma and macromolecules leading to vasogenic edema and microbleeds. Posterior circulation is more prone to autonomic dysreflexia because of its meagre sympathetic
TE D
innervation.
Although hypertension thought to be initiating cause of PRES, mean arterial pressure in most hypertensive PRES patients stays within normal autoregulatory response limits. [10]
EP
Interestingly, the degree of vasogenic edema as well did not co-relate with severity blood
AC C
pressure. [11] Of note, PRES has also been reported in patients with normal BP. [12] Bartynski et al believe that a complex systemic inflammatory response involving activation of T-cells and certain inflammatory cytokines leading to systemic vasoconstriction and hypoperfusion may be the underlying mechanism in such normotensive-PRES cases. [13] Few authors have proposed that left-sided tumors are more prone to result in PRES postoperatively. [8] However, our case suggests that laterality of the tumor plays no role in development of PRES following surgery. Also, it is interesting to note that majority (9 out of
ACCEPTED MANUSCRIPT 10) of the previously reported cases are males. So, male gender predilection in this rare condition still needs to be investigated. Sorour et al have described ‘delayed’ onset of PRES on POD 8 of vestibular schwannoma surgery. [8] To our knowledge, an ‘unusually prolonged delay’ months after the surgery has
RI PT
never been reported earlier. A high index of clinical suspicion and low threshold for radiological investigation helped us clinch the diagnosis in our case.
Even though several pathophysiological mechanisms have been proposed earlier, none of
SC
them fully explain the development of PRES in our case. We believe that rapid recurrence of the residual tumor leading to brainstem distortion may have lead to such findings in our
histopathological diagnosis. [Figure 3]
M AN U
patient. Such an unusual presentation in a vestibular schwannoma even made us review our
Hedna et al have established that PRES is associated with brain hypoperfusion based upon CT perfusion studies and may even mimic stroke!! [14] Therefore, it becomes imperative to
TE D
identify promptly and aggressive management of this frequently reversible condition to avoid subsequent neurological sequalae.
To conclude, PRES should be considered among possible complications of posterior fossa
EP
tumor surgery which presents with acute neurological symptoms. With correct diagnosis in
AC C
time and aggressive treatment, most patients achieve complete neurological recovery within 1-3 months and clinical improvement often precedes resolution of lesions radiologically.
References
1. Hinchey J,
Chaves
C,
Appignani
B,
et
al.
A
reversible
posterior
leukoencephalopathy syndrome. N Engl J Med 1996;334(8): 494–500. 2. Moriarity JL Jr, Lim M, Storm PB, Beauchamp NJ Jr, Olivi A. Reversible
ACCEPTED MANUSCRIPT posterior leukoencephalopathy occurring during resection of a posterior fossa tumor: case report and review of the literature. Neurosurgery 2001;49(5):1237– 1239; discussion 1239–1240. 3. Patel AJ, Fox BD, Fulkerson DH, et al. Posterior reversible encephalopathy
RI PT
syndrome during posterior fossa tumor resection in a child. J Neurosurg Pediatr 2010;6(4):377–380.
4. Gephart MG, Taft BP, Giese AK, Guzman R, Edwards MS. Perioperative
SC
posterior reversible encephalopathy syndrome in 2 pediatric neurosurgery patients
M AN U
with brainstem ependymoma. J Neurosurg Pediatr 2011;7(3):235–237. 5. Sánchez-cuadrado LL, Royo A, Cerdeño V, Roda JM, Gavilán J. Reversible posterior leukoencephalopathy syndrome after lateral skull base surgery. Otol Neurotol 2011;32(5):838–840.
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ACCEPTED MANUSCRIPT 9. González Quarante LH, Mena-Bernal JH, Martín BP, Ramírez Carrasco M, Muñoz Casado MJ, Martínez de Aragón A, de las Heras RS. Posterior reversible encephalopathy syndrome (PRES): a rare condition after resection of posterior fossa tumors: two new cases and review of the literature. Childs Nerv Syst. 2016
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Encephalopathy Syndrome Resolving Within 48 Hours in a Normotensive Patient Who Underwent Thoracic Spine Surgery. Journal of Clinical Medicine Research. 2016;8(3):263-266. WS.
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14. Hedna VS, Stead LG, Bidari S, et al. Posterior reversible encephalopathy syndrome (PRES) and CT perfusion changes. International Journal of Emergency Medicine 2012;5:12.
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4th ventricle ependymoma
Day of onset Day of surgery
Radiological involvement Parieto-occipital
Recovery period 2 months
Moriarity et al. 2001 [2]
19/Male
Patel et al. 2010 [3] 6/Male
Cerebellar juvenile pilocytic astrocytoma
Day of surgery
Parieto-occipital, Temporal cortex
3 months
Gephart et al. 2011 [4]
4/Male
4th ventricle grade III ependymoma
Day 7
7/Male
4th ventricle grade II ependymoma
Day 5
Parieto-occipital with speckled contrast enhancement Holohemispheric and cerebellar
58/Male
Day 4 Adenoid cystic carcinoma (right external auditory canal with intracranial extension)
Sanchez-Cuadrado et al. 2011 [5]
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Histo-pathology
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Age/sex
Occipital, cerebellar
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Study
3 months
1 month 2 weeks
Not reported. 4th ventricular tumor
Day 8
Parieto-occipital, Basal ganglia
Kuhnt et al. 2013 [7]
63/Male
Two infratentorial hemangiopericytomas
Day of surgery
Parieto-occipital, 1 week Rostral paramedian mesencephalon and pons
Sorour et al. 2013 [8]
57/Female Giant acoustic schwannoma
Day 2
Parieto-occipital
1 month
Quarante et al. 2015 [9]
4/Male
Day 9
Parieto-occipital
1 month
Day 2
Diffusely involving both hemispheres Diffusely involving both hemispheres
1 month
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Avecillas-Chasín et 19/Male al. 2013 [6]
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Present case
Posterior fossa medulloblastoma Grade II ependymoma (fourth ventricle)
23/Female Acoustic schwannoma
8 months
1 month
2 weeks
Table 1: A summary of previously reported cases of PRES associated with various posterior fossa tumor surgeries.
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Figure 1: Pre-operative MRI T1- & T2- weighted images (axial, coronal & saggital views) showing large solid-cystic vestibular schwannoma reaching causing mass effect on brainstem
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with proximal ventriculomegaly. [A-C] Immediate post-operative contrast CT head (axial
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and saggital views) suggestive of gross total resection of the tumor with well-formed surgical cavity. [D, E] At 3 month follow-up, T2WI axial view MRI shows recurrence of tumor causing distortion of the brainstem. [F]
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Figure 2: Non-contrast CT head done in emergency 8 months after surgery showing diffuse
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subcortical edema involving bilateral frontal, & parieto-occipital lobes with no ventriculomegaly. Ventricular shunt tip is also seen in the frontal horn. [A, B] Axial view T2WI MRI image showing increase in the size of recurrent tumor measuring about 5 x 4 cm
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along with enlargement of cystic component posteriorly as well as medially (Blue arrows) causing brainstem compression with mild effacement of 4th ventricle. [C] On T2-weighted
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MRI image (axial view), bilateral frontal and parieto-occipital lobes were found to have diffuse subcortical edema with hyperintense area in left parieto-occipital region. [D] There was evidence of micro bleeds seen on SWAN sequence. [E] MR venography did not reveal any signs of thrombosis of cortical veins or deep venous sinuses. [F] MR angiogram (coronal and lateral views) showing normal vasculature in anterior as well as posterior circulation. [G, H]
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Figure 3: Microphotograph of hematoxylin and eosin stained section showing tumor
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composed of spindle cells disposed in vaguely alternating cellular and hypocellular areas. Tumor cells showed oval to elongated nuclei, bland chromatin, inconspicuous nucleoli and
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moderate amount of cytoplasm. Occasional verocay bodies, composed of palisaded nuclei and few blood vessels were noted in the stroma. There was no evidence of increased mitotic activity, necrosis or malignancy.
ACCEPTED MANUSCRIPT Highlights:
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A rare clinical condition with uncertain pathophysiology in which patient presents
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with heterogeneous clinical findings.
Associated with various conditions like hypertension, eclampsia, sepsis, electrolyte
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imbalances, autoimmune diseases and immunosuppressive therapy.
So far, only 10 cases of various posterior fossa tumor surgery have presented with
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PRES intra-operatively or within a week of surgery.
We are reporting the very first case of “unusually delayed” clinical presentation of
Also, we have proposed “Rapid tumor recurrence leading to rostral medulla
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compression” as a new pathophysiological mechanism of this entity.
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this rare condition 8 months after vestibular schwannoma surgery.
ACCEPTED MANUSCRIPT Abbreviations:
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Posterior reversible encephalopathy syndrome – PRES Rostral ventro-lateral medulla – RVLM Emergency department – ED Post-operative day – POD Blood-brain barrier - BBB
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• • • • •