Temporary Lumbar Drain as Treatment for Pediatric Fulminant Idiopathic Intracranial Hypertension

Several ophthalmic findings including optic disc swelling, globe flattening and choroidal folds have been observed in astronauts following long-duration space flight. The authors now report asymmetric choroidal expansion, disc swelling and optic disc morphologic changes in a 45-year-old astronaut which occurred during long-duration space flight and persisted following his space mission. Case study of ocular findings in an astronaut documented during and after a long-duration space flight of approximately 6 months. Before, during and after his spaceflight, he underwent complete eye examination, including fundus photography, ultrasound, and optical coherence tomography. We documented asymmetric choroidal expansion inflight that largely resolved by 30 days postflight, asymmetric disc swelling observed inflight that persisted for over 180 days postflight, asymmetric optic disc morphologic changes documented inflight by OCT that persisted for 630 days postflight and asymmetric globe flattening that began inflight and continued 660 days postflight. Lumbar puncture opening pressures obtained at 7 and 365 days post-mission were 22 and 16 cm H20 respectively. The persistent asymmetric findings noted above, coupled with the lumbar puncture opening pressures, suggest that prolonged microgravity exposure may have produced asymmetric pressure changes within the perioptic subarachnoid space.

Original Contribution Temporary Lumbar Drain as Treatment for Pediatric Fulminant Idiopathic Intracranial Hypertension Kim Jiramongkolchai, MD, Edward G. Buckley, MD, M. Tariq Bhatti, MD, Carrie R. Muh, MD, MS, Robert E. Wiggins, MD, Pawina Jiramongkolchai, MD, Mays A. El-Dairi, MD Abstract: Fulminant idiopathic intracranial hypertension (FIIH) is a subtype of idiopathic intracranial hypertension (IIH) characterized by rapid, severe, progressive vision loss. Surgical intervention is often performed either as a cerebrospinal fluid (CSF) shunt procedure or an optic nerve sheath fenestration or, at times, both. These surgical procedures carry a significant risk of morbidity and failure. We present 2 patients in whom a temporary lumbar drain was successfully used in the management of medically undertreated pediatric FIIH, and circumvented the need for surgical intervention. Journal of Neuro-Ophthalmology 2017;37:126-132 doi: 10.1097/WNO.0000000000000457 © 2016 by North American Neuro-Ophthalmology Society F ulminant idiopathic intracranial hypertension (FIIH) is a subtype of IIH characterized by acute, rapidly progressive, and profound vision loss. Given the high risk of permanent vision impairment, Thamibsetty et al (1) recommended surgical intervention within 5 days of onset of Departments of Ophthalmology (KJ, EGB, MTB, MAE), Neurology (MTB), and Neurosurgery (CRM), Duke University Medical Center, Durham, North Carolina; Asheville Eye Associates (RW), Asheville, North Carolina; and Department of Otolaryngology (PJ), Washington University School of Medicine Otolaryngology, St. Louis, Missouri. Portions of this work were presented in poster format at the North American Neuro-ophthalmology Society Meeting, February 24, 2015, San Diego, CA. M. A. El-Dairi is a consultant for Prana pharmaceuticals and is a recipient of the Knights Templar Foundation Award (7/2015-7/ 2016); M. T. Bhatti is a speaker and consultant for Novartis Pharmaceuticals; K. Jiramongkolchai is the recipient of the Heed Research Fellowship Award (7/2015-7/2016); C. R. Muh is a recipient of the Coulter-Duke Translational Partnership Grant and the Duke Institute for Brain Sciences Research Incubator Award and is a consultant for Cyberonics, Inc. The remaining authors report no conflicts of interest. Address correspondence to Mays A. El-Dairi, MD, Duke University Eye Center, DUMC 3802, Durham, NC 27710; E-mail: mays.el-dairi@ dm.duke.edu 126 symptoms. Lumboperitoneal shunt (LPS) or ventricular peritoneal shunt (VPS) have been recommended for patients with severe headaches associated with visual loss, and optic nerve sheath fenestration (ONSF) is reserved for those with primarily vision loss (1-4). However, these procedures may lead to significant morbidity. VPS and LPS are associated with risk of shunt failure and the need for surgical revision, and ONSF with visual loss and ocular motility disturbances (2,5-8). We report the successful management of 2 pediatric patients with FIHH using a temporary lumbar drain (LD) as an alternative form of treatment. REPORT OF CASES Patient 1 A 13-year-old obese girl with a body mass index (BMI) of 37.8 kg/m2 was diagnosed with doxycycline-induced intracranial hypertension with resultant headaches and blurry vision for 6 weeks. She was prescribed acetazolamide, 750 mg twice a day, by her ophthalmologist. After 2 weeks, she was referred for progressive constriction of her visual fields and decreased vision in both eyes. On examination, visual acuity was light perception, right eye and 20/80, left eye. She could recognize 12/14 color plates with her left eye, and there was a right relative afferent pupillary defect. Funduscopic examination disclosed severe papilledema (Frisén Grade 5) (Fig. 1A, B). Optical coherence tomography (OCT) showed marked peripapillary retinal nerve fiber layer (RNFL) thickening (Fig. 1C, D) and subretinal fluid in each macula with photoreceptor changes (Fig. 1E, F). Brain MRI and magnetic resonance venography (MRV) results were normal. Lumbar puncture revealed an opening pressure of greater than 55 cm H2O with normal cerebrospinal fluid (CSF) composition. Jiramongkolchai et al: J Neuro-Ophthalmol 2017; 37: 126-132 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. Patient 1. A and B. There is severe papilledema in both eyes. C and D. Optical coherence tomography (OCT) demonstrates peripapillary retinal nerve fiber layer thickening bilaterally. E and F. OCT of the maculas shows subretinal fluid and photoreceptor changes in both eyes. G and H. One week after placement of a lumbar drain, OCT of the maculas reveals decreased subretinal fluid but persistent photoreceptor changes. Because of the acute and severe vision and visual field loss, the patient was given 1 g intravenous methylprednisolone (IVMP) per day for a total of 6 days and acetazolamide 2 g daily. An LD was placed and titrated to drain a target of 15 mL CSF/hour. One day after placement of the LD, vision at near was hand motion, right eye, and 20/40, left eye. For the first 8 days, the LD was titrated to 15 mL CSF/hour, followed by 5 mL CSF/hour for 1 day, 3 mL CSF/hour for 1 day, and then was clamped for 1 day. Ten days after the placement of the LD, vision at near improved to 20/70, right eye, with eccentric fixation and 20/25, left eye. The following day, her opening pressure on lumbar puncture (LP) ranged from 10-15 cm H2O, and the LD was removed. The patient's headaches lessened for the first 8 days after LD placement and then resolved. Of note, on post-LD day 5, she developed a small CSF leak that required resuturing of the drain. OCT of the maculas showed decreased subretinal fluid but persistent photoreceptor changes in both eyes (Fig. 1G, H). She was discharged on acetazolamide 1,000 mg twice daily. Eighteen months later, vision had stabilized at 20/200, right eye and 20/50, left eye. Both Jiramongkolchai et al: J Neuro-Ophthalmol 2017; 37: 126-132 optic discs were pale (Fig. 2A, B). OCT showed RNFL thickness of 61 mm, right eye, and 57 mm, left eye (normal: 90- 100 mm) (Fig. 2C). In addition, the volume of the retinal ganglion cell-inner plexiform layer (RGC-IPC) complex was reduced, right eye = 0.89 mm3 and left eye = 0.34 mm3 (pediatric normative database mean = 1.31 ± 0.10 mm3). Kinetic perimetry showed constricted visual fields, bilaterally (Fig. 2D, E). Patient 2 A 13-year-old obese girl with BMI 42.5 kg/m2 was diagnosed with IIH. While on acetazolamide 500 mg twice daily for 2 weeks, she complained of new-onset vision loss and headaches and was referred to our neuro-ophthalmology service. Examination documented acuity of 20/400, right eye and count finger at 5 feet, left eye. There was a left relative afferent pupillary defect, a left abduction deficit, and bilateral papilledema (Frisén Grade 5) (Fig. 3A, B). OCT showed swollen RNFL in each eye (Fig. 3C, D) and subretinal fluid and photoreceptor changes bilaterally (Fig. 3E, F). Visual fields were severely constricted bilaterally 127 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 2. Patient 1, 18 months after lumbar drain. A and B. There is bilateral optic disc pallor. C. Optical coherence tomography shows retinal nerve fiber layer thinning in both eyes. D and E. Kinetic visual fields demonstrate constriction, bilaterally. RNFL, retinal nerve fiber layer; OD, right eye; ONH, optic nerve head; OS, left eye; OU, both eyes. (Fig. 3G, H). Brain MRI and MRV results were normal. Lumbar puncture showed an opening pressure of 37 cm H2O with normal CSF analysis. The patient was given IVMP 1 g per day for 3 days, and acetazolamide was increased to 1 g twice daily. An LD was placed and titrated to drain 10-15 ml CSF/hour. One day after placement of the LD, vision at near had improved to 20/200 in each eye. Three days later, near vision was 20/70 bilaterally. Because of the improvement in vision, the LD was removed. It had averaged 11.1 ml CSF drained per hour during the 4 days when it was in place. The patient did not experience any adverse effects of LD placement or removal. There was a marked decrease in papilledema, and acetazolamide was continued at 2 g daily. 128 Three weeks later, vision was 20/70, right eye and 20/60, left eye. However, 2 months after the LD was removed, vision acuity in the left eye declined to 20/400 but remained stable at 20/70 in the right eye. In both eyes, there was optic disc pallor with gliosis and optocilliary shunt vessels and macular exudates (Fig. 4A, B). Spontaneous venous pulsations were seen only in the right eye. OCT showed reduced swelling of the RNFL in both eyes (Fig. 4C, D). In addition, there was resolution of subretinal fluid with photoreceptor changes and new inner nuclear layer cysts (Fig. 4E, F). Volume of the RGC- IPL complex was decreased, right eye = 0.74 mm3 and left eye = 0.60 mm3 (pediatric normative database mean = 1.13 ± 0.10 mm3). Kinetic visual fields remained constricted but were improved compared with those obtained Jiramongkolchai et al: J Neuro-Ophthalmol 2017; 37: 126-132 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 3. Patient 2. A and B. There is marked papilledema bilaterally. C and D. Optical coherence tomography (OCT) demonstrates swelling of the retinal nerve fiber layer in both eyes. E and F. OCT of each macula shows subretinal fluid and altered photoreceptors. G and H. Kinetic visual fields are severely constricted. before placement of the LD (Fig. 4G, H). Repeat LP revealed an opening pressure of 48 cm H2O, and vision in the left eye improved to 20/100. Given the elevated intracranial pressure and the improvement in vision in Jiramongkolchai et al: J Neuro-Ophthalmol 2017; 37: 126-132 the left eye after the lumbar puncture, a left ONSF was performed. Two months postoperatively, visual acuity was 20/60, right eye, and 20/80, left eye, with spontaneous venous pulsations in both eyes. 129 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 4. Patient 2, two months after lumbar drain. A and B. The optic discs are pale with optociliary shunt vessels. C and D. Optical coherence tomography (OCT) shows diminished swelling of the retinal nerve fiber layer bilaterally. E and F. Macular OCT reveals inner nuclear layer cysts and photoreceptor changes. G and H. Kinetic visual fields are constricted but improved compared with visual fields obtained before placement of a lumbar drain. 130 Jiramongkolchai et al: J Neuro-Ophthalmol 2017; 37: 126-132 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution DISCUSSION FIIH is a form of IIH characterized by rapid and severe progressive visual loss occurring in 2.2%-2.9% of cases (1). In the largest case series of FIIH with 16 patients, the time between the onset of symptoms to the nadir of visual loss ranged from 7 to 28 days with a mean of 16.1 days. The median time from evaluation in the neuro-ophthalmology clinic to surgery, with either shunt placement or ONSF, was 3 days with a range of a few hours to 37 days. Importantly, patients legally blind at follow-up had a mean surgical delay of 6.5 days, whereas patients who were not legally blind had a median delay of 2 days. Therefore, although there is no prospective clinical data regarding treatment of FIIH, immediate surgery has been recommended to prevent further visual loss (1,9,10). However, ONSF, LPS, and VPS are associated with serious potential complications and have been shown to eventually fail in a large proportion of patients (11). Complication rates for ONSF range from 4.8% to 45% (mean 12.9%) (8), and include transient diplopia because of injury of an extraocular muscle in 29%-35% of reported cases (12-14), pupillary abnormality in 11% (14,15), and vision loss in up to 11%, with permanent vision loss in 1.5%-2.6% (13,14,16-20). Failure rate of ONSF resulting in worsening visual acuity or visual field has been reported to occur in approximately 10% of patients (21). Complications of VPS and LPS include shunt obstruction, overshunting leading to intracranial hypotension, infection, CSF leak, cerebellar tonsillar herniation, lumbar radiculopathy, catheter migration resulting in abdominal pain/bowel perforation, subdural hemorrhage, subarachnoid hemorrhage, and intracerebral hematoma (22-29). One report documented that at 2 years following shunt placement, 75% had failed (86% of LPS and 44% of VPS) (30). It is our protocol to start lumbar drainage at a rate of 10-15 ml CSF/hour. Before removal of the drain, we decrease fluid output to test how the patient will do without CSF diversion. In our 2 patients, a temporary LD was successful in managing visual loss and headaches. Although the final vision and visual fields were improved in both patients, neither patient recovered normal visual function. We hypothesize that both patients already had irreversible damage to the optic nerves by the time they had presented to us. Both patients had volume loss of the RGC-IPL complex, and also demonstrated foveal photoreceptor loss on presentation, which limited their visual recovery. It is unclear from other reported cases of FIIH why some patients fail medical treatment. However, as demonstrated in the patient 2, these individuals should be followed very closely for an extended period to detect for any progressive visual loss which would require surgical intervention. Other temporary CSF diversion procedures include serial lumbar punctures, large volume lumbar punctures, and external ventricular drains (EVDs). The disadvantage of serial lumbar punctures is that they are uncomfortable and Jiramongkolchai et al: J Neuro-Ophthalmol 2017; 37: 126-132 painful for many patients, and in obese patients, lumbar punctures are technically challenging. Large volume lumbar punctures and repeated lumbar punctures also have a minimal overall effect as CSF is replenished within 6 hours (31). EVDs are technically challenging in this patient population, as these individuals tend to have very small ventricles (32). There is a 10% risk of hemorrhage with EVD placement, and a more than 20% risk of hemorrhage with EVD removal (33). Compared with these other approaches, a temporary LD offers the advantage of titratable control of CSF volume in a monitored setting while avoiding an intracranial procedure (9). In addition, an LD can be used as a diagnostic tool to determine whether elevated intracranial pressure is the cause of the headache and whether a permanent CSF diversion procedure will be beneficial. As with any procedure, lumbar drainage is associated with complications. Major complications occur in approximately 3% of patients and minor complications in 5% (34). Significant complications include neuraxial hematoma in 3.2% of patients (35), catheter fracture in 0.1%-3.2%, (36,37), CSF leak in 0.3%, (37,38), meningitis in 0.2%- 3%, (37), and intracranial hemorrhage in 1%-3.2% (35,39). Minor complications include nerve root irritation in 2.6% and low-pressure headache in 1.7% (34). Both of our patients received IVMP concurrent with placement of an LD. One could argue that an LD might preclude the need for steroids. However, based on the literature, IVMP seems to have a beneficial effect on highgrade papilledema (40-44). The mechanism of this effect is not proven but is thought to increase CSF absorption by the arachnoid granulations (45). In conclusion, we believe that a temporary LD should be considered in the management of patients with FIIH and rapid vision loss. These patients still require close follow-up over an extended period to monitor for further visual decline. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: M. A. El-Dairi, K. Jiramongkolchai, M. T. Bhatti, C. R. Muh, P. Jiramongkolchai, and E. G. Buckley; b. Acquisition of data: M. A. El-Dairi, K. Jiramongkolchai, M. T. Bhatti, C. R. Muh, and R. Wiggins; c. Analysis and interpretation of data: M. A. El-Dairi, K. Jiramongkolchai, M. T. Bhatti, C. R. Muh, P. Jiramongkolchai, and E. G. Buckley. Category 2: a. Drafting the article: M. A. El-Dairi, K. Jiramongkolchai, M. T. Bhatti, and C. R. Muh; b. Revising it for intellectual content: M. A. El-Dairi, K. Jiramongkolchai, M. T. Bhatti, C. R. Muh, P. Jiramongkolchai, E. G. Buckley, and R. Wiggins. Category 3: a. Final approval of the completed article: M. A. El-Dairi, K. Jiramongkolchai, M. T. Bhatti, C. R. Muh, P. Jiramongkolchai, E. G. Buckley, and R. Wiggins. REFERENCES 1. Thambisetty M, Lavin PJ, Newman NJ, Biousse V. Fulminant idiopathic intracranial hypertension. Neurology. 2007;68:229-232. 2. Uretsky S. Surgical interventions for idiopathic intracranial hypertension. 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