- Department of Neurosurgery, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
DOI:10.25259/SNI_483_2019Copyright: © 2020 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Alexandra Rose Lyons, Sarah Louise Olson. Parinaud syndrome as an unusual presentation of intracranial hypotension. 09-May-2020;11:98
How to cite this URL: Alexandra Rose Lyons, Sarah Louise Olson. Parinaud syndrome as an unusual presentation of intracranial hypotension. 09-May-2020;11:98. Available from: https://surgicalneurologyint.com/surgicalint-articles/10012/
Background: Vertical gaze palsy is a rare clinical manifestation of intracranial hypotension. The typical features of intracranial hypotension include a postural headache, dural enhancement, and low cerebrospinal fluid (CSF) opening pressure.
Case Description: We describe a case of a shunt-dependent middle-aged female with aqueductal stenosis who developed recurrent presentations of upgaze palsy with postural headaches, confirmed low opening pressure, and slit ventricles on magnetic resonance imaging (MRI) due to shunt overdrainage. Her ophthalmoplegia and headaches improved following third ventriculostomy and with increasing the shunt opening pressure to prevent excess CSF drainage.
Conclusion: Intracranial hypotension should be considered part of the differential diagnosis for patients presenting with an upgaze palsy.
Keywords: Intracranial hypotension, Ophthalmoplegia, Parinaud syndrome, Slit ventricle, Upgaze palsy, Ventriculoperitoneal shunt
Parinaud syndrome (also called dorsal midbrain syndrome and pretectal syndrome) is primarily characterized by a supranuclear vertical conjugate gaze paralysis. Other features include upper eyelid retraction (Collier’s sign), dissociated pupillary response to light (pseudo-Argyll Robertson pupil), and a convergence and accommodation palsy.[
In the case of hydrocephalus, the third ventricle enlarges producing direct and/or indirect pressure through displacement of the suprapineal recess causing compression of decussating posterior commissure fibers responsible for bilateral conjugate vertical gaze.[
computes impulses ascending from the vestibular system through the MLF and descending fibers from the cerebral hemisphere (mainly frontal eye field) through the pretectum to finalize gaze commands[
(a) Saccades – visual stimuli in the occipital cortex gets processed in the parietal eye field located in the posterior parietal cortex. The frontal eye field then initiates ocular motor saccades after integrating information from the parietal eye field (spatial targeting where to look), supplementary eye field and dorsolateral prefrontal cortex (latter two involved in decision making and planning movements). Direct excitation of the superior colliculus leads to the stimulation of the mesencephalic (riMLF for vertical) or pontine (horizontal) reticular formations which results in coordinated saccadic eye movement. An indirect pathway goes through the caudate and basal ganglia. The substantia nigra pars reticulata prevents saccade generation through inhibition of the superior colliculus; however, stimulation of the caudate nucleus from the frontal eye field inhibits the substantia nigra and hence this pathway. (b) Smooth pursuit – The striate cortex of the occipital lobe commences early motion analysis of visual stimuli. The temporal eye field (middle temporal and medial superior temporal areas) then integrates information to calculate velocity and direction of the object. The frontal eye field initiates motor execution after also receiving contributions from the supplementary eye field and dorsolateral prefrontal cortex which plan and track motion. Corticopontine fibers synapse on the dorsolateral pontine nuclei which project signals to the cerebellum (flocculus, paraflocculus, and fastigial nuclei), then to vestibular nuclei which modulate and coordinate cranial nerve nuclei for extraocular movement. This allows tracking of an object with constant feedback to adjust speed and direction of ocular movements so smooth pursuit of an object can occur. Note gaze centers are not part of this pathway.
Along with medial and superior vestibular nuclei, the perihypoglossal nuclei are thought to have an influence on the integration of vertical eye movement commands. It receives fibers from the paramedian pontine reticular formation, vestibular nuclei, and the nucleus of Darkschewitsch and has both direct and indirect excitatory influence on ocular motor neurons.[
The cerebellum has contributions affecting vertical eye movements. The fastigial nuclear complex receives vestibulocerebellar fibers and projects back to the vestibular nuclei through the cerebellovestibular tract. It likely has involvement in generation and execution of vertical saccades. Experimental lesions of this area have resulted in oblique trajectory of attempted vertical eye movement.[
Other supranuclear pathologies which affect structures involved in vertical gaze include progressive supranuclear palsy, multiple sclerosis, pineal tumor, vascular accidents (posterior thalamo-subthalamic paramedian artery supplies bilateral riMLF territories), parkinsonism, encephalitis, and drugs (carbamazepine and barbiturates).[
Consideration of vertical gaze deficits in relation to the anatomical region of the midbrain is another approach to reviewing pathology [
Despite it being generally useful to use the paradigm, whereby downgaze represents tegmental pathology and upgaze represents tectal pathology,[
This report describes a case of a middle-aged female with recurrent presentations of partially reversible Parinaud syndrome associated with intracranial hypotension due to shunt overdrainage.
A 47-year-old female presented with a 2-week progressive history of blurred vision, horizontal diplopia, inability to look upward, slowed mentation, and a postural headache on standing. There were no nausea, decreased consciousness, limb neurology, or fevers.
She was initially diagnosed with idiopathic intracranial hypertension at the age of 41 (2012); however, on later imaging, it became apparent that the underlying pathology was aqueductal stenosis. A ventriculoperitoneal (VP) shunt was inserted in 2012 and required two revisions, one in 2013 and 2017. After the 2017 shunt revision for kinked shunt tubing, she had recurrent admissions for intracranial hypotension symptoms with reproducible symptomatology of blurry vision, cognitive decline, postural headache, and an upgaze palsy. Shunt interrogation confirmed that the shunt was working in early 2018, so the shunt valve pressure was consequently increased to 7 to reexpand the ventricles to a normal size. This adjustment, however, resulted in acute ventriculomegaly with a drop in Glasgow Coma Scale indicating shunt dependence, so the setting was reduced back to 4 which improved her conscious state and symptoms, with her ventricles returning to slit-like size on CT. On MRI later in 2018, she was found to have new fluid-attenuated inversion recovery (FLAIR) signal changes in bilateral optic nerves and the midbrain [
Previous MRI (a) High-resolution T2 MRI showing cerebral aqueduct stenosis/web. (b) Axial FLAIR MRI showing abnormal signal in the optic chiasm extending to bilateral optic tracts and in the midbrain from the interpeduncular fossa extending between the red nuclei to the area of the oculomotor nuclei.
Other medical history included anxiety, depression, and asthma. She was taking no regular medications, however, self-ceased fluoxetine a couple of months ago due to fatigue side effects. There were no allergies. She is nonsmoker with occasional alcohol intake. Occupation is a phlebotomist.
On examination, she was found to have an almost complete upgaze paralysis bilaterally with torsional nystagmus (more prominent in the left eye) and painful convergence- retraction nystagmus on attempted upgaze. The upgaze palsy could be overcome with the doll’s eye maneuver. At rest, there was bilateral inferior deviation of her eyes. There was a convergence and accommodation paresis. The patient experienced horizontal diplopia maximally when trying to accommodate and look up. Her left eye had exotropia on upgaze; however there was no strabismus at rest. Smooth pursuit extraocular movements horizontally and downwards were normal. Pupils were equal and reactive to light, there was no light-near dissociation or relative afferent pupillary defect. Ophthalmologist review revealed no papilledema or refractive error causing the blurred vision. Intraocular pressures were normal, visual acuity 6/6 bilaterally. The rest of the cranial nerve examination was normal, as was limb neurology. There was no postural drop in blood pressure.
CSF culture had no growth, protein was low at <0.07, otherwise, cell counts and glucose were normal. Blood tests were normal including a pituitary panel with the exception of gonadotropins showing a perimenopausal pattern. Shunt series XR showed no disconnection of the shunt or CSF collection in the abdomen. CT brain showed slit lateral and third ventricles, no intracranial hemorrhage and confirmed that the tip of the catheter was in the ventricle. MRI brain showed no ischaemia, tumour, or lesions in the area of the dorsal midbrain. There were no FLAIR changes or evidence of mechanical distortion from brain ‘sag’ [
Clinically, she has Parinaud syndrome. The convergence insufficiency and accommodation palsy were likely responsible for her blurred vision and diplopia. The differential diagnosis was between an overdraining shunt and an underdraining/ malfunctioning shunt in the context of slit ventricle syndrome. The final diagnosis of overdrainage causing intracranial hypotension was based on the postural symptoms which correlated with low CSF opening pressures, a functioning shunt, lack of papilledema, and the MRI finding of slit ventricles. During her admission, the VP Codman Certas shunt settings were changed from 4 to 5 which gave her marked improvement with nystagmus, postural symptoms, and the ability to move her eyes above midline when looking up, however, not full resolution of the upgaze palsy [
The characteristic diagnostic triad of intracranial hypotension is a positional headache (exacerbated by upright posture and coughing), dural enhancement with gadolinium, and low CSF opening pressures.[
There are three other documented cases where intracranial hypotension has presented with an upgaze palsy. Fedi et al. (2008) depicted a middle-aged woman with reversible Parinaud syndrome from intracranial hypotension secondary to a ruptured T11/12 perineural cyst. Gupta et al. (2014) presented a case of shunt overdrainage causing parkinsonism and Parinaud syndrome with persistence of the upgaze palsy despite improvement of her other ophthalmoplegia signs and postural symptoms with shunt ligation. Bray et al. (2016) described a case of spontaneous intracranial hypotension with associated dorsal midbrain venous infarction presenting with an upgaze palsy.[
The amount of brain “sag” explains some of the varying presentations of intracranial hypotension from infrequent postural headaches to stupor.[
The transient FLAIR changes seen in the MRI following the episode of acute hydrocephalus may have contributed to her presentation of Parinaud syndrome and decreased visual acuity on that occasion. However, they fail to explain previous and ongoing presentations of Parinaud syndrome and blurred vision without the FLAIR abnormality. FLAIR sequence suppresses CSF and intensifies T2-weighted images so abnormalities in the subarachnoid space and brain-CSF boundary become more apparent. In the context of intracranial hypotension, especially following intracranial hypertension, an elevated blood pool-to- CSF ratio can cause sulcal FLAIR hyperintensity.[
Optokinetic nystagmus is a reflex oscillation in response to motion in the visual field, whereby the body tries to stabilize an image on the retina. Optokinetic nystagmus response occurs when an object being tracked visually by the eyes reaches the limit of vision and, not being able to comfortably pursue the object anymore, the eyes rapidly return to a neutral position with a reflex saccade. There are two main pathways responsible for optokinetic nystagmus: direct retinal fibers to the pretectum (nucleus of the optic tract) and a cortical pathway mediated through the occipital lobe. A key feature of Parinaud syndrome is convergence retraction nystagmus which, with optokinetic nystagmus testing, presents as an abnormal optokinetic response which facilitates the diagnosis.[
Shunt underdrainage and overdrainage are a common result in shunt-dependent patients with fine tuning of opening valve pressures and occasionally different types of shunts required to find the right balance of CSF drainage for each individual patient. Long-term shunt overdrainage can lead to craniosynostosis in children, slit ventricle syndrome, subdural hematomas, and intracranial hypotension symptoms. There is 10–12% incidence of one of these complications occurring in the initial 6.5 years following the first shunt insertion.[
Slit (collapsed) ventricle syndrome is a complication of chronic shunt overdrainage. Given the depletion of CSF within the ventricular spaces, the surface tension increases (as with collapsed alveoli in the lung) due to Laplace’s law, it, hence, requires more intraventricular pressure to overcome the tension within the wall of the ventricle for expansion to occur.[
Intracranial hypotension should be considered part of the differential diagnosis for patients presenting with an upgaze palsy. This is especially prominent in patients with intracranial shunt devices in situ where overdrainage is a common phenomenon.
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1. . Available from: https://www.aao.org/bcscsnippetdetail.aspx?id=9ccbbaa3-a369-485c-b3e8-b80e69c19978 [Last accessed on 2019 Oct 23].
2. Antony J, Hacking C, Jeffree RL. Pachymeningeal enhancement-a comprehensive review of literature. Neurosurg Rev. 2015. 38: 649-59
3. Barmack NH. Inferior olive and oculomotor system. Prog Brain Res. 2006. 151: 269-91
4. Bergsneider M, Miller C, Vespa PM, Hu X. Surgical management of adult hydrocephalus. Neurosurgery. 2008. 62: 643-60
5. Bray TJ, Chandrashekar H, Rees J, Burke A, Merve A, Thust S. Venous infarction mimicking a neoplasm in spontaneous intracranial hypotension: An unusual cause of parinaud’s syndrome. J Surg Case Rep. 2016. 2016: rjw037-
6. Danchaivijitr C, Kennard C. Diplopia and eye movement disorders. J Neurol Neurosurg Psychiatry. 2004. 75: 24-31
7. Fedi M, Cantello R, Shuey NH, Mitchell LA, Comi C, Monaco F. Spontaneous intracranial hypotension presenting as a reversible dorsal midbrain syndrome. J Neuroophthalmol. 2008. 28: 289-92
8. Gold DR.editors. Eye movement disorders: Conjugate gaze abnormalities. Liu, Volpe, and Galetta’s Neuro- ophthalmology. Amsterdam: Elsevier; 2019. p. 549-84
9. Gupta M, Patidar Y, Khwaja GA, Chowdhury D, Batra A, Dasgupta A. Intracranial hypotension due to shunt overdrainage presenting as reversible dorsal midbrain syndrome. Neurol Asia. 2014. 19: 107-10
10. Hill L, Gwinnutt C. Cerebral blood flow and intracranial pressure. Update Anaesth. 2007. 24: 30-5
11. Kheradmand A, Zee DS. Cerebellum and ocular motor control. Front Neurol. 2011. 2: 53-
12. Kompf D, Caplan LR, Hopf HC.editors. Oculomotor syndromes in rostral brain-stem lesions. Brain-stem Localization and Function. Berlin: Springer; 1993. p. 107-17
13. Leigh R, Gross M.editors. Eye movement disorders. Encyclopedia of Neuroscience. Amsterdam: Elsevier; 2009. p. 169-77
14. Lloyd-Smith Sequeira A, Rizzo JR, Rucker JC. Clinical approach to supranuclear brainstem saccadic gaze palsies. Front Neurol. 2017. 8: 429-
15. London R. Optokinetic nystagmus: A review of pathways, techniques and selected diagnostic applications. J Am Optom Assoc. 1982. 53: 791-8
16. Mccrea RA, Baker R, Delgado-Garcia J. Afferent and efferent organization of the prepositus hypoglossi nucleus. Prog Brain Res. 1979. 50: 653-65
17. Mokri B. The monro-kellie hypothesis: Applications in CSF volume depletion. Neurology. 2001. 56: 1746-8
18. Mustari MJ, Fuchs AF, Kaneko CR, Robinson FR. Anatomical connections of the primate pretectal nucleus of the optic tract. J Comp Neurol. 1994. 349: 111-28
19. Ozyigit A, Michaelides C, Natsiopoulos K. Spontaneous intracranial hypotension presenting with frontotemporal dementia: A case report. Front Neurol. 2018. 9: 673-
20. Pudenz RH, Foltz EL. Hydrocephalus: Overdrainage by ventricular shunts. A review and recommendations. Surg Neurol. 1991. 35: 200-12
21. Smith SVGeorge RNguyen KLee AGKini AAl-Zubidi N. Available from: https://www.eyewiki.aao.org/vertical_gaze_palsy [Last accessed on 2019 Apr 10].
22. Stuckey SL, Goh TD, Heffernan T, Rowan D. Hyperintensity in the subarachnoid space on FLAIR MRI. AJR Am J Roentgenol. 2007. 189: 913-21
23. Swash M. Disorders of ocular movement in hydrocephalus. Proc R Soc Med. 1976. 67: 480-4
24. Yazdani M, Stalcup ST, Chatterjee AR, Matheus MG. Sulcal FLAIR hyperintensity after CSF removal in two patients with intracranial hypertension. Eur J Radiol Open. 2019. 6: 33-5