Medical Strategies and Surgical Interventions in Idiopathic Intracranial Hypertension: A Prospective Comparative Study

Transcription

1 Medical Strategies and Surgical Interventions in Idiopathic Intracranial Hypertension: A Prospective Comparative Study Hatem Samir 1, Sherif Kamel 2, Ayman Enab 3 Departments of Neurology 1, Ophthalmology 2, Neurosurgery 3, Cairo University ABSTRACT Objective: To evaluate the outcome of patients with idiopathic intracranial hypertension who adopted medical therapy comparing to those who underwent either optic nerve sheath decompression or lumboperitoneal shunt. Methods: In a prospective study, 28 Egyptian patients with the syndrome of idiopathic intracranial hypertension were enrolled. They underwent intensive neuro-ophthalmological examination, visual field assessment, neuro-radiological evaluation and spinal tap. They received maximum medical therapy for 3 months; thereafter, patients who failed to respond to medical therapy were subjected to surgical interventions (optic nerve sheath decompression if the main complaint was visual; or lumboperitoneal shunt if headache was the main morbidity). Patients were followed up for 18 months. Results: The headache and the visual status improved significantly in all included patients throughout the follow-up period. Those who adopted medical therapy showed no recurrence or worsening of their symptoms as long as they were maintained regularly on treatment, and the doses of acetazolamide were reduced in 40% of them after one year of stabilization of their condition, with no evidence of recurrence. Patients who were subjected to optic nerve sheath decompression or lumboperitoneal shunt showed measurable improvement without serious complications in their follow-up period. Conclusions: Medical treatment, optic nerve sheath decompression and lumboperitoneal shunt are complementary modalities, a conjoint work should provide the rational decisions in saving vision and relieving symptoms in patients with idiopathic intracranial hypertension. (Egypt J. Neurol. Psychiat. Neurosurg., 2006, 43(1): ) INTRODUCTION Idiopathic intracranial hypertension (IIH) is vision-threatening disease of unknown etiology that affects predominantly obese women of childbearing age 1,2. The female dominance was reported by Durcan et al. 3 and Radhakrishnan et al. 4, who recorded the female-to-male ratio as high as 8:1. Current theories concerning the pathogenesis of elevated intracranial pressure include increased resistance to cerebrospinal fluid (CSF) outflow at the arachnoid granulations through which CSF reabsorption is thought to occur by bulk flow. Alternatively the role of occult cerebral venous outflow abnormalities that might produce IIH was emphasized 5. Idiopathic intracranial hypertension is a syndrome of increased intracranial pressure without hydrocephalus or mass lesion with elevated CSF pressure but with normal chemical and cellular composition 6. It is usually presented by headache and papilledema, and occasional sixth nerve palsy with an otherwise normal 91

2 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 neurological examination; this forms the basis of the modified Dandy criteria for the diagnosis of IIH 7. It usually responds to medical therapy over months or years, but the disease process sometimes leads to serious visual loss due to papilledema and compression of the optic nerve fibers 8. The medical therapy includes weight control, non-ketotic diet, discontinuation of contributing medications, serial lumbar punctures, provision of carbonic anhydrase inhibitors and diuretics, steroids, and certain analgesics (6,9). In addition, some authorities believed that digoxin has a beneficial effect in lowering CSF pressure and it is associated with fewer adverse effects 10. When medical therapy fails with evidence of progressive deterioration of visual function; surgical procedures should be considered. However; management of cases refractory to medical treatment is difficult, and some patients are subjected to repeated neurosurgical procedures attempting to reduce intracranial pressure 11. Neurosurgical procedures used to alleviate intracranial pressure include subtemporal decompression, lumboperitoneal shunts, parietal flaps 12, and recently the venous sinus stenting 2. However, Lumboperitoneal shunt is the traditional method for providing prompt reduction of intracranial pressure (ICP) in patients with IIH 13. Although visual improvement was recorded in a good percent of cases; yet, vision is not always saved in many cases after a successful functioning shunting procedure 12. The other surgical option is optic nerve sheath decompression (ONSD), which has a good potential for reversal of visual loss 14,15. This procedure is simple without great morbidity and with low rate of complications and also has a long term stability of the results 16,17. The procedure involves cutting slits in the dura surrounding the optic nerve immediately behind the globe; which allows CSF flow into the orbital fat to be absorbed into the venous circulation. However; headache is not reliably relieved by this approach 18. Wall 19 reported that patients failing medical therapy have optic nerve sheath fenestration performed if visual loss is the main morbidity. Shunting procedures are considered if headache is the main symptom. The aim of this work, is to assess the outcome of patients with idiopathic intracranial hypertension comparing patients adopted medical therapy to those who underwent either optic nerve sheath decompression or lumboperitoneal shunt. SUBJECTS AND METHODS Study Design and Patient Selection This was a prospective (longitudinal) study on therapeutic modalities of idiopathic intracranial hypertension; that compared the outcome in patients adopted medical strategies, optic nerve sheath fenestration and lumboperitoneal shunting procedure. It included 28 Egyptian patients presented with idiopathic intracranial hypertension, drawn in the period between March 2002 and April 2004, and they were followed up for at least 18 months. Criteria for diagnosis of IIH included the presence of papilledema and headaches; all patients had documented raised CSF pressure (>250 mm / CSF) measured by spinal tap. CSF analysis was done (cytology and chemistry) with parallel blood sugar level just before the procedure 2. Exclusionary Criteria. (1) Ventricular enlargement or an intracranial mass on imaging, (2) evidence of venous sinus thrombosis (3), abnormal CSF constituents and (4) patients with irregular follow-up [patients were considered irregular when one follow-up visit was missed]. Patient Enrollment and Initial Evaluation. Initially we included 41 patients, 13 patients were missed in one of their follow-up visits and they were not subjected to any surgical intervention, but they were excluded from the study. All the other 28 patients enrolled in this study were submitted to the following: 92

3 Neurological Assessment. This include thorough history taking of headache characters, associated symptoms, and intensity according to Blanchard and Andrasik 20, history of transient visual obscurations (TVOs), and double vision. It also includes funduscopic assessment, visual acuity, pupillary reactions, ocular motility, other cranial nerves involvement, and signs of lateralization. In addition body mass index (BMI) was calculated according to the following formula 21 : Body Weight (Kg) (Height [M]) 2 Ophthalmological Assessment. Fifty six eyes of the included 28 patients have been evaluated. Eyes were assessed for the degree of papilledema with fundus photographs, intraocular pressure measurement, visual acuity, pupillary reaction, and field of vision. According to severity of papilledema, eyes were divided into (1) early papilledema, (2) acute fully developed papilledema, (3) chronic papilledema and (4) atrophic papilledema: that has furtherly divided into 3 groups; (i) atrophic papilledema on top of chronic papilledema, (ii) atrophic papilledema on top of acute papilledema and (iii) postpapilledemic optic atrophy 22. Visual Field Testing. Using the Humphrery automated perimeter. The test strategy used was the full threshold test 24-2 test strategy. It evaluates the mean deviation of retinal sensitivity (MD) in each eye, and the size of blind spot. The mean deviation (MD) was used to evaluate the deterioration and improvement according to Spoor and McHenry 23, taking (-/+ 2) of MD as a significant worsening or improvement. Radiological Assessment. All patients included in this work had had brain computerized tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance venography (MRV). Laboratory Tests. Include complete blood picture, fasting and post-prandial blood sugar, hormonal profile; when clinically indicated, coagulation profile and parallel blood sugar level just before spinal tap. For patients receiving diuretics, serum potassium level was periodically assessed. Spinal Tap. Lumbar puncture (LP) was done under complete aseptic conditions using a 20-gauge needle, and carried out while the patient in the left lateral decubitus position assuming a fetal posture. The procedure was explained to the patients and the location for needle insertion was identified by palpation between the two spinous processes of L4 and L5 levels. The area was prepared carefully and draped, measuring CSF opening pressure was done, CSF pressure was measured using LP manometer, and CSF samples were obtained. When sufficient fluid was obtained, the needle was withdrawn and a dry sterile dressing was applied to the puncture site. The frequency of LP and amount of CSF withdrawn were determined for each patient individually 24. Medical Management. All 28 patients received maximum medical therapy with modest dieting and following a lowsalt regimen with caution against overuse of fluids. The carbonic anhydrase inhibitor [acetazolamide] was used for 4 weeks, this was accompanied by repeating of spinal tap for 6 patients. If no clinical improvement was documented steroids were added to the treatment 25, in addition to Furosemide (lasix) as a second-line agent 1,7,19 for another 8 weeks. Thereafter, patients were reassessed neurologically and ophthalmologically, and by using visual field testing. Follow up and Assessment. 93

4 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 Patients broadly fell into three categories based on classifications adopted by Higgins et al. 2 into (1) asymptomatic with resolution of headache and visual impairment, (2) improved with some residual headache and/or visual impairment not requiring further intervention, and (3) no change or worsening of headache intensity or visual impairment. Patient Categorization. Accordingly; patients were divided into two groups; (1) the responder group (Group I) (11/28), who experienced resolution or improvement of headache (no headache or intensity 1), with documented improvement of visual function, and (2) the non-responder group (Group II) (17/28) showed mild non-satisfactory improvement, no changes or even worsening of either headache or visual function. According to the main morbidity in the non-responder patients [Group II], surgical intervention was decided; patients with visual loss was the main symptomatology [8/28] were subjected to ONSD and continued on medical therapy, while those with headache was the main symptomatology [9/28] were subjected to lumboperitoneal shunting procedure (1,19). Optic Nerve Sheath Decompression (ONSD). Eight patients (8/28) were subjected to this procedure, when the vision and field loss is progressive despite the received maximal medical therapy. Eleven surgeries were done in the 8 patients, 6 patients had unilateral surgery while 2 patients had bilateral surgeries; and one eye was operated twice. All patients were kept on same doses of medical therapy post-operatively. Surgical Technique. The medial transconjunctival approach was used in all cases, with a controllable eyelid speculum was used to open the eyelid. A single incision over the insertion of the medial rectus extending from the upper to the lower fornices without release incisions. Disinsertion of the medial rectus muscle with a double armed 6-0 Vicryl leaving a muscle stump of about 1 mm is left for the intrascleral suture. Intrascleral traction suture (5-0 non-absorbable) passed through the scleral stump of the medial rectus muscle taking partial thickness of the sclera. The traction on the globe was limited to 30 to 60 seconds and the interval between traction periods was 15 to 30 seconds. Because of the frequent cutting of the suture through the muscles stump, one suture is passed through the stump until the middle and another suture is passed from the other end of the muscle stump to meet the other suture in the middle. A retinal detachment retractor was used to retract the medial rectus and the medial orbital contents medially. The intrascleral course of the long posterior ciliary artery was used for orientation in finding the nerve sheath. The operating microscope was focused along this line to reach the sheath. Multiple incision technique was used by a microvitreo-retinal blade starting from 2 mm behind the globe and extended for about 5mm not exceeding 8mm behind the globe making 3 incisions. The initial CSF gush was seen in most of the cases. The medial rectus was reattached with closure of the conjunctiva. Subconjunctival getamicin and decadron were given in the lower fornix in all cases 26. Full ophthalmological examination was done in the first postoperative day with the exception fundus photography and visual field test. The Lumboperitoneal Shunt (LPS). Initially 9 patients (9/28) were subjected to this procedure when symptoms of headache are prominent and refractory to medical therapy. Another one patient who was on irregular intake of medical therapy was subjected to LPS one year later as she experienced increase of headache intensity and deterioration of visual field that was associated with increase in CSF pressure. All patients post-operatively were drugs-free. Surgical Technique. The patient is placed on the lateral decubitus position. The spine is moderately flexed to open the interlaminar spaces; and pads are placed in the axilla and at the anterior part of the abdomen to 94

5 support the patient s position. A special one-piece shunt is used and the lumbar catheter is placed by a percutaneous technique, using a Tuohy cannula in the passage of the tube or by a small open laminectomy. The Tuohy cannula is introduced with the tip parallel to the longitudinal fiber direction of the dura to avoid CSF leakage. The ability of the lumbar tube to move through the cannula should be checked before shunt placement. A small laminotomy is necessary in between to open the dura under direct vision. The dome and peritoneal part are tunneled subcutaneously from the lumbar spinal area to the side of the abdomen, a 3 cm subcostal skin incision is done, and the subcutaneous tissue is divided, the muscle fascia opened sharply and the muscle fibers divided by blunt dissection until the peritoneum. The peritoneum is grasped by hemostats (Kochers) and opened very carefully with scissors to avoid damage to the intestines. A thin absorbable purse-string suture is placed in the peritoneum, and the catheter is pushed lightly in to the peritoneal cavity. The peritoneum is secured by a purse-string suture and the muscle fascia, subcutis and skin are closed in the usual way 27. Post-operative Assessment. Headache evaluation and the change in frequency and severity were recorded. Visual symptoms were assessed and visual field examination was performed 2 weeks postoperatively with the same parameters mentioned before. Fundus photography was done after field examination in the same day. Long-term Follow-up. Visual field testing was repeated every 3 months or when there was any doubt of visual deterioration. Detailed headache assessment in a structured interview and full neurological examination were done in every session. Follow up of patients was performed for at least 18 months after initial enrollment. Statistical Analysis: Data analysis was carried out with the Statistical Package for Social Sciences (version 10.0, 1999; SPSS Inc. Chicago, IL, USA). Descriptive Statistics: Mean + SD, number and percentage; Analytic tests using the independent t- test, Pearson correlation coefficient (r) was done for all continuous data and the probability (p) was obtained from the tables according to the degree of freedom and so significance was calculated. Analysis of variance (ANOVA) used for making comparison between 3 or more samples with posthoc test to detect significant group. In nonparametric variables, X 2 chi square test was used for the nominal data and Mann-Whitney test was used for the ordinal data. P-value < 0.05 was considered significant. RESULTS A) Clinical Characteristics. Twenty-eight patients were included in the current study, (23 females 82.1%, and 5 males 17.9% ); the mean age was years (with range from 20 to 37 years). The initial presentations of all included patients were headache and visual symptoms, the duration of symptoms ranging from 2 to 13 months with a mean of months. Asymmetric visual affection was detected in 11 patients (39.29%). Basic clinical characteristics are shown in table (1). B) Patient Assessment. Field evaluation showed bilateral enlargement of blind spot in all included patients. The means of baseline field affection using the mean deviation (MD) of retinal sensitivity in included patients were (range ) in right eye, and (range ) in the left eye. The basic mean deviation of retinal sensitivity in each eye, basic documented CSF pressure, and radiological assessment for included patients is shown in table (2). Correlation of Degree of papilledema and MD: There is highly significant correlation 95

6 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 between the degree of papilledema and the affection of visual field measured by MD of the retinal sensitivity (P<0.001), which documented the reliability of the tested field. C) Patient Management and Outcome Assessment. Maximum medical therapy was advocated for all included patients, the dose of Acetazolamide ranged from 1250 mg to 2000 mg per day. Four patients received short course of steroids (1 mg/kg prednisolone for 2 weeks and then tapered gradually over another 2 weeks); and 10 patients received add on furosemide [serum potassium was regularly checked]. Six patients (6/28) were subjected to repeated spinal tap [2 to 4 times over one month] and withdrawal of 15 c.c CSF fluid was done in each time. Patients were assessed after 12 weeks of initiation of medical therapy by headache diary, funduscopic evaluation and visual field testing. Eleven patients (11/28) experienced improvement or resolution of symptoms [Group I] (Responder Group), in this group no adverse events of medications were encountered. The other seventeen patients (17/28) showed mild non-satisfactory improvement, no changes or even worsening of either headache or visual function [Group II] (Non-Responder Group); in this group, 5 patients were subjected to repeated spinal tap to relieve their symptoms, 3 patients received steroids, and 7 patients received add on furosemide. Two patients in this group experienced side effects of therapy, one experienced hypotension, and the other stopped acetazolamide because of a very agonizing paresthesia. The difference between the two groups in basic characteristics is shown in table (3). The shorter the duration of illness, the milder the degree of papilledema, the lesser affection of visual field, the lower the basic CSF pressure, and the less frequently needed repeated spinal tap for initial improvement of symptoms were significantly reported in responder group. Though there is no statistical significant difference between the responder patients to medical therapy and those who were subjected to surgical intervention regarding the BMI, yet, 12 patients in the non-responder group are in category II, and III obesity, while, only 4 in responder are in same categories. Assessment of Medically-Responding Patients. One of those patients had initially sixth nerve paresis, that rapidly responding to repeated spinal tap short course of steroids and diuretics. None of the medically responding patients had any neurological deficits or visual symptoms after 3 months of medical therapy. The headache intensity and MD (visual field testing) showed statistically significant improvement in the responder group. Table (4). Surgical Intervention. Eight patients were subjected to ONSD and continued on medical therapy. Six patients had unilateral surgery [the worse eye or that with RAPD] while 2 patients had bilateral surgeries. Whereas 9 patients were subjected to lumboperitoneal shunting procedure and post-operatively they were drugs-free. Post-operative Assessment. Symptomatology Outcome. Headache intensity assessment and visual field testing were done 2 weeks post-operatively; shows postoperatively. Measurable improvement was detected in all patients regarding the headache intensity, visual symptoms and the mean of MD in both groups (Table 5). After ONSD, one patient (1/8) experienced marked improvement of headache intensity that was associated with reduction of acetazolamide, other 7 patients received the same dose of acetazolamide and one of them was kept on add on frusemide. After LPS, non of those patients was on diuretics, and they experienced significant headache improvement. All patients with preoperative TVOs experienced complete recovery of this condition after surgery (either ONSD or LPS) irrespective of the grade of papilledema and visual improvement. Three cases had an afferent 96

7 pupillary defect (10.7%), the eye with the RAPD was always the eye with the more affected visual functions, the three patients were subjected to ONSD, and two of them improved after surgery and pupillary reactions were normal. The remaining one eye had no improvement. In ONSD, the unoperated eye showed improvement in response to surgery in the fellow eye; and all eyes with atrophic papilledema that improved after surgery had residual field defects. Postoperative Complications: ONSD. Complications of surgery was divided into: (1) intra-operative and (2) postoperative complications. (1) Intraoperative complications. (a) Difficult exposure was experienced in one of our eyes, (b) massive intraorbital hemorrhage did not happen in any of our cases. However, bleeding from the cut dural edges was seen in nearly all our cases with great variability. (2) Postoperative complications. (a) Lid and conjunctival edema occurred in all eyes of variable severity and duration, (b) transient horizontal motility disorder was found in two operated eyes; but all eyes the defect was reversed without residual, (c) no vascular complications had occurred in this work, (d) there was one surgical failure, and surgery was done twice; in this patient exposure was difficult and a thin membrane of fibrous tissue at the fenestration site covered the optic nerve sheath. After the second ONSD, the patient experienced mild improvement in visual field test. No long-term complications were encountered for 15 months after surgery. Shunting Procedure. One patient experienced post-operative superficially infected abdominal wound, which managed by systemic antibiotics and completely resolved. No other complications were encountered in short-term follow up period. D) Long-Term Follow up: Follow up (over 12 months). Headache intensity assessment, neurological and ophthalmological examination, and visual field tests were done every 3 months. Over a period of one year after the initial assessment, none of our 28 patients had recurrent visual symptoms or newly-developed headaches, and no one was on more than the initial dose of Acetazolamide. After 6 months only five patients had mild headache [2 patients were on medical therapy and one underwent ONSD and on regular treatment, and 2 patients with LPS and on no medications], there was no evidence of visual deterioration, those patients responded well to nonsteroidal antiinflammatory drugs and propranolol. Tables (6) and (7) showed the visual field assessment (using the means of MD of retinal sensitivity) after 6 and 12 months of initial assessment, respectively. There was no statistically significant difference between patients who were on medical therapy, and those who underwent surgical interventions. Follow up (after 18 months). One patient who was on medical therapy experienced increase of headache intensity and deterioration of visual field that was associated with increase in CSF pressure [this patient was non-compliant on therapy]; and she was subjected to LPS; another patient who underwent shunting procedure had the shunt obstructed and it was revised once. Doses of acetazolamide were reduced in 4 patients out of responder (4/10) to 750 mg/d after one year of stabilization of their condition, with no evidence of recurrence, the other 6 patients were kept in the same doses, as upon trying to reduce the dose, they encountered increase in their headache intensity but with no visual symptoms. All patients with LPS on no therapy, and 2 patients of ONSD were on reduced doses of acetazolamide (750 mg/d), while other 6 patients were on same doses. There was no deterioration in either visual functions or headache intensity; the five patients who had mild headache were kept on propranolol with less frequent attacks in their headache diary. Also, there was no statistically significant difference between patients who were on medical therapy, and those who underwent surgical interventions (Table 8). 97

8 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 Table 1. Basic clinical characteristics of the included patients. No. Age (Y)/ Sex BMI Other risk factors Duration [mo] Adopted Therapy Visual Symptoms Headache intensity Neurologic deficits Papilledema Grading 1 30/M 2 5 ME Blurring /F 3 8 ME Blurring /F 2 HT 3 ME TVO /F 1 HT 10 S - Acuity 5 V neuralgia 4 (i) /F 3 - PTH 2 ME Blurring /F 4 4 ME Sparkling /F 5 3 ME TVO /M 3 6 ME Diplopia 5 6 th N palsy /F 3 MI 2 ME TVO /F 4 4 ME TVO /F 2 7 OD Blurring /F 3 HT 9 OD TVO 3 RAPD (Lt) 3 4 (i) 13 35/F 5 HT 6 S Diplopia 5 6 th N palsy /F 5 HT 5 S Blurring 4 V neuralgia /F 5 HT 7 S Diplopia 5 6 th N palsy /M 4 6 S TVO /M 4 4 S TVO /F 5 5 S TVO /F 5 MI 7 OD TVO /F 5 6 ME S Blurring /F 2 HT 13 OD - Acuity 3 4 (iii) /F 3 HT 9 OD - Acuity 4 RAPD (Rt) 4 (i) /M 4 3 S Diplopia 5 6 th N palsy /F 5 2 OD - Acuity 1 RAPD (Rt) 4 (ii) /F 4 5 S TVO /F 3 4 ME Blurring /F 5 HT 3 OD TVO /F 4 HT 6 OD TVO Right (Rt) Left (Lt) M: MALE, F: FEMALE. BMI [body mass index]: (1) normal [ ], (2) pre-obese [ ], (3) obese class I [ ], (4) obese class II [ ], (5) obese class III [> 40] Kg / m2. HT: Hormonal Therapy (for contraception), MI: Menstrual Irregularity, - PTH: Hypoparathyroidism. ME: medical therapy. S: lumboperitoneal shunt, OD: optic nerve decompression. TVO: Transient Visual Obscurations. RAPD: Relative Afferent Pupillary Defect. V neuralgia: trigeminal neuralgia. 98

9 Table 2. Basic visual field, CSF pressure, and radiological data. No. Visual Field Testing Initial CSF Pressure Radiology MD Right (OD) MD Left (OS) (cm/csf) Normal Normal Normal Normal Bilateral calcification of BG Normal Attenuated ventricles (R) Normal Empty sella Normal Normal Normal (R) Attenuated ventricles Normal Normal (R) Attenuated ventricles Normal (R) Attenuated ventricles Empty sella Normal Empty sella (R) Attenuated ventricles Normal (R) Empty sella Normal Attenuated ventricles Normal Attenuated ventricles. MD: Mean Deviation of Retinal Sensitivity. OD: right. OS: left. BG: Basal Ganglia. (R): spinal tap was repeated. 99

10 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 Table 3. The difference between the medically responders and the non responders in basic characteristics. Group I Group II P value Age (mean + SD) Duration (mean + SD) BMI Normal 0 1 Pre-obese 2 2 Obesity (I) Obesity (II) 2 5 Obesity (III) 2 7 Headache intensity Degree of Papilledema (RIGHT) Degree of Papilledema (LEFT) MD (RIGHT) MD (LEFT) CSF pressure Table 4. Comparison between the medically responders and the non responders in both headache intensity and visual field. Responder (n=11) Non-responder (n=17) Initially After 3 mo P-value Initially After 3 mo P-value Headache Intensity MD (RIGHT) MD (LEFT)

11 Table 5. Headache intensity and visual field assessment pre- and post-operatively in the surgically treated patients. ONSD (n=8) LPS (n=9) Preoperative Post-operative P-value Preoperative Post-operative P-value Headache Intensity MD (Right) MD (Left) Table 6. Visual field assessment in patient groups after 6 months of initial assessment. Medical therapy (n=11) ONSD (n=8) LPS (n=9) P value MD (Right) MD (Left) Table 7. Visual field assessment in patient groups after 12 months of initial assessment. Medical therapy (N=11) ONSD (N=8) LPS (N=9) P value MD (Right) MD (Left) Table 8. Visual field assessment in patient groups after 18 months of initial assessment. Medical therapy (N=10) ONSD (N=8) LPS (N=10) P value MD (Right) MD (Left) DISCUSSION Idiopathic intracranial hypertension remains an enigmatic diagnosis of exclusion. Prompt diagnosis and thorough evaluation and treatment are crucial for improving the condition. The most important goal of both medical and surgical therapies is to prevent or arrest progressive visual loss 9. The aim of this work is to compare the outcome in patients adopted medical therapy and those who underwent either lumboperitoneal shunt or optic nerve sheath decompression. Twenty-eight patients were included in the current study, their mean age was years (range from 20 to 37), which goes in accordance with the range of age in which the diagnosis of IIH is documented 2,28,29,30,31. The female dominance was noted in this study as well as other similar studies 19,29,32 ; in our series, 82.1% of our patients were females; Carta et al. 30 reported 80 % of their patients were females; 101

12 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 whereas, Galvin and Van Stavern 31 reported a higher incidence reached up to 92.2%; while other studies reported female-to-male ratio up to 8:1 3,4. Obesity is an important factor contributing to IIH development and has a major impact on disease progression and might affect prognosis. The annual incidence of IIH was reported to be 0.9 per 100,000 population; which increases to 7.9 per 100,000 obese women 4. In our study, 23 patients out of 28 were obese (82.1%). Merle et al. 33 (1998) found 75% of their patients were obese; while Galvin and Van Stavern 31 found that obesity was described in 87.8% of their patients. In our study, obesity was more detected in patients who were subjected to surgical intervention. Curry et al. 34 reported that obesity is a major risk factor for IIH, and they recognized that incidence of CSF shunting for IIH is increasing in the United States at about the same relative rate as morbid obesity; in addition, they recommended further studies to establish the best shunting method and to explore alternative treatment strategies, such as optic nerve sheath fenestration and bariatric surgery. On the same track; Shin and Balcer 1 emphasized that bariatric surgery could be an effective treatment for IIH in obese patients. Headache and visual symptoms were present in all cases in this study; the most common neurological deficit was abducens nerve paresis and it was found in 4 patients (14.3%), this goes in accordance with Digre and Corbett 35, who reported that diplopia due to sixth nerve palsy occurs in about 10% to 30% of patients. Transient visual obscurations (TVOs) were present in 12 patients (42.9%), which is less than what was previously reported by Corbett et al. 36, who reported that TVOs could be a presenting feature or develop in the course of the disorder in up to 72%. This discrepancy could be attributed to the duration of illness and the earlier intervention in our study as the maximum duration in our series is 13 months with a mean of months. Relative afferent papillary defect (RAPD), which is a valuable objective evidence of visual loss is present only in only 3 patients (10.7%) and it was always present on the side of worse visual functions. Moreover; asymmetric visual affection was detected in 39.29% of cases. Asymmetric or even unilateral papilledema was previously described by many authorities Lepore 38 hypothesized that in those patients one optic nerve is relatively protected from pressure effects by optic nerve sheath anomalies or lamina cribrosa changes due to increased collagen and decreased elasticity. We reported two patients with trigeminal neuralgic-like symptoms; this was not considered as an exclusionary criterion for the diagnosis of IIH, and it was previously reported 40. We also described a case with hypoparathyroidism associated with manifestations of IIH, this patient was presented with the syndrome of IIH associated with muscle cramps, her brain CT scan showed bilateral calcifications of basal ganglia; she was kept on calcium and vitamin D with Acetazolamide; she markedly improved with subsequent reduction of the dose of acetazolamide. This association between hypoparathyroidism and IIH was documented since 1950s In the current study, there were 4 patients (14.3%) with radiological evidence of empty sella, without any abnormalities in their hormonal assay. This finding is a common association with IIH, and it is usually innocuous 45. In the current study, 17 patients (60.7%) were subjected to surgical interventions. It is noteworthy that this high percentage does not represent the true incidence of medically intractable cases and two considerable issues should be emphasized, the first is that we actually enrolled 41 patients, and 13 patients were irregularly followed up and hence excluded, but they were not subjected to any surgical interventions; the second is the adopted criteria for measuring the improvement of field testing according to Spoor and McHenry 23, which taking (-/+ 2 of MD) as a significant worsening or improvement and thus limit the continuation of medical therapy in mildly improved patients. Basically; the therapeutic choice for IIH is an intriguing issue; as there is insufficient information to generate an evidence-based 102

13 management strategy for idiopathic intracranial hypertension and several different treatments have been proposed ranging from relatively conservative measures to more invasive treatments; and properly designed trials are needed 32. It has been recognized that long-term treatment, side effects, possible severity of the ocular disease, difficulties of dietary restriction and the high rate of recurrence, which reached up to 50% would indicate a need to reconsider surgical treatment 33. On the other view; Wall 19 reported that most patients respond well to medical therapy, however, they added that IIH may recur throughout life. Moreover; Mezaal and Saadah 46 recognized that IIH has relatively benign course and more aggressive treatment is not recommended. The milder visual affection, the lower the basic CSF pressure and the less frequently needed repeated spinal tap for initial improvement of symptoms were significantly reported in responder group; also the shorter the duration of illness between first presentation and medical intervention the more the chance of responding to medical therapy; which propose earlier intervention might help in preventing the progression of the disease and saving vision through relief of the axoplasmic flow stasis and ischemia in the viable fibers of optic disc 47. However; it is very uncommon that one can know exactly when a bout of intracranial hypertension begins and the duration of symptoms before the diagnosis is made varies from few weeks to more than a year 48. Long-Term Follow-up. Patients who were maintained on medical therapy showed no recurrence as long as they were on regular intake of medications, no documented cases with deterioration except when medical therapy was discontinued or irregularly received, which was detected in one patient who was subjected to LPS; during the 18 months follow-up, the doses of acetazolamide were reduced in 4 patients (4/10) with no evidence of recurrence. These findings emphasized that IIH requires long-term maintenance on medical therapy to prevent recurrence; however, dose reduction could be tried after stabilization of the condition; this was previously reported by Kesler et al. 49, who studied the long-term prognosis of 54 patients with IIH over a mean observation period of 6.2 years, they found that 33 patients had two or more recurrences, but these did not occur while patients were maintained on acetazolamide. Optic Nerve Sheath Decompression. The unilateral 6 surgeries were done in the more affected eyes; whereas, the bilateral surgeries were done because those patients had a bilateral serious visual deterioration. All the eyes in this work had improved visual field; in one eye, in which surgery was done twice, after the second ONSD, field of vision was mildly improved. We reported one patient with headache improvement after ONSD. Optic nerve sheath decompression is not a surgery for headache relief. If it does, headache relief should be viewed as a bonus on top of visual recovery 14. The effect of ONSD on visual field is far beyond any doubt as proved in this work and other similar studies 50,51. In the current study, the unoperated eyes in those with unilateral surgeries showed improvement in response to surgery in the fellow eye. Goh et al. 18 recognized that cutting slits or rectangular patches in the dura surrounding the optic nerve immediately behind the globe will allow egress of CSF directly into the orbital fat where it is absorbed into the venous circulation; however, reduction of CSF pressure does not consistently detected, and headache is not reliably relieved by this approach. They added that despite general lack of CSF pressure -lowering effect, papilledema in both eyes may regress following fenestration of one optic nerve. Furthermore; in this work all eyes with atrophic papilledema showed improvement in the visual field tests but with residual defects. This might conclude that surgery is indicated in cases of atrophic papilledema, without waiting for the results of medical therapy because this may jeopardize the remaining vision of the patient. A white flat disc is not hopeless because inside this atrophic disc there may be viable fibers suffering 103

14 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 only axoplasmic flow obstruction and their number may not be sufficient to cause ophthalmoscopically visible disc swelling 16,52,53. The medial transconjunctival approach was adopted, as most of the recent literature recommends, as it is much easier and time saving 16,54. During of this work, most of the cases were done through multiple incisions rather than window removal technique; as it has lower time consumption, less manipulation, and less traction on the globe; which minimize vascular complications of surgery; however, the preference between incisions and window removal may be a personal surgical preference 15. In our study, further modifications on the current technique was adopted; this include (a) reduction of the size of the conjunctival incision to about 90 degrees, with subsequent minimal postoperative chemosis and lid edema, (b) changing the direction of traction from anterolateral to lateral or even posterolateral to avoid exposure of vascular structures attached to the nerve sheath to stretch, (c) using the modified double baseball suture; which provides a more stable traction without the possibility of cutting through the insertion at one end because of the 4-point traction. In the current work, we have one surgical failure due to difficult exposure, other complications included bleeding from the cut dural edges and lid and conjunctival edema of variable degree that were detected in almost all operated eyes and they were mild and transient. In two operated eyes, transient horizontal motility disorder was found which was reversed without residual. No long-term complications were encountered. Our results go in accordance with what was reported by Banta and Farris 55, who concluded that optic nerve sheath decompression is a safe and effective means of stabilizing visual acuity and the visual fields of those tested. In the current work, patients who underwent ONSD were kept on medications; this should be considered in choosing surgical intervention in those who were medically non-responding. Optic nerve sheath fenestration is a filtration surgery and it improves visual function in patients with IIH who experience deteriorating visual acuity and fields in spite of medical therapy 18. Lumboperitoneal Shunt. This procedure is an effective mean of acutely lowering intracranial pressure and providing prompt reduction of ICP in patients with IIH. In the current work, manifestations of increased ICP that include headaches, visual symptoms and field tests were improved in all included patients, another major advantage of LPS is withdrawal of all medications post-operatively. Two patients (2/10) experienced complications, one had post-operative superficially infected abdominal wound, and the other had the shunt obstructed and it was revised once. No serious or other long-term complications were encountered in this study. Burgett et al 13 recognized that the major drawback of LP shunting is the need for frequent revisions in a few patients, and this poor shunt tolerance is detected in certain individuals of unclear reasons. Though, lumboperitoneal shunting is considered as a first surgical choice for patients with IIH 13 ; yet, some neurosurgeons prefer ventriculoperitoneal shunt over lumboperitoneal shunting; the reasons for this preference are that these shunts can be monitored for function using an extracranial subcutaneous compressible bulb, moreover, the use of ventricular shunts was associated with a lower risk of shunt obstruction and revision 56. However; other neurosurgeons are reluctant to place ventricular shunts in patients with IIH because the ventricles are small and difficult to cannulate without radiographic guidance and they recommended the use of lumboperitoneal shunting 9,13,57. Whatever the surgical choice cerebrospinal fluid (CSF) diversion procedures are the mainstay of treatment in IIH after more conservative measures have failed. These reduce intracranial pressure regardless the pathogenic mechanisms responsible for the disease 2. Comparing ONSD with the classic technique of CSF diversion; in the former, it is limited to the orbital area and the intracranial pressure remains unchanged. The complications are different, yet 104

15 analysis of the literature shows the same efficacy in terms of visual function 58. Hence; the choice between optic nerve fenestration and lumboperitoneal shunting or both remains unresolved, in some cases optic nerve fenestration was required before or after lumboperitoneal shunting to relieve pressure on the optic nerve 59. Another considerable point is that in our study, we detected patient with improved headache following ONSD. In the current study; after more than one year follow-up no significant difference was observed between patients maintained on medical treatment, those underwent ONSD and those with CSF derivation. In conclusion; idiopathic intracranial hypertension is a chronic disease that requires long-term maintenance on medical therapy to prevent recurrence, most patients usually respond to medical therapy as long as it is maintained and tolerated; optic nerve sheath fenestration and lumbar peritoneal shunt are effective surgical means to reduce the pressure on the optic disc in patients who were intolerant to medical therapy or when clinical deterioration was detected, with long-term equal efficacy. The three modalities are complementary to each others and a neurologist, a neurosurgeon and an ophthalmologist should work together to provide the evidence on which to base rational decisions in the care of patients with idiopathic intracranial hypertension. REFERENCES 1. Shin RK, and Balcer LJ (2002): Idiopathic Intracranial Hypertension. Curr Treat Options Neurol; Jul,4(4): Higgins JNP, Cousins C, Owler BK, Sarkies N and Pickard JD (2003): Idiopathic intracranial hypertension: 12 cases treated by venous sinus stenting. J Neurol Neurosurg Psychiatry;74: Durcan FJ, Corbett JJ and Wall M (1988): The incidence of pseudotumor cerebri. Population studies in Iowa and Louisiana. Arch Neurol; Aug,45(8): Radhakrishnan K, Thacker AK and Bohlaga NH (1993): Epidemiology of idiopathic intracranial hypertension: a prospective and case-control study. J Neurol Sci; May,116(1): Walker RWH (2001): Idiopathic intracranial hypertension: any light on the mechanism of the raised pressure?. J Neurol Neurosurg Psychiatry; 71: Tang RA, Dorotheo EU, Schiffman JS and Bahrani HM (2004): Medical and surgical management of idiopathic intracranial hypertension in pregnancy. Curr Neurol Neurosci Rep; Sep;4(5): Lim M, Kurian M, Penn A, Calver D and Lin JP (2005): Visual failure without headache in idiopathic intracranial hypertension. Archives of Disease in Childhood; 90: Hayreh MS, and Hayreh SS (1977): Optic disc oedema in raised intracranial pressure. Evolution and resolution. Arch Ophthalmol; 95: Binder DK, Horton JC, Lawton MT and McDermott MW (2004): Idiopathic intracranial hypertension. Neurosurgery; Mar,54(3): Schott GD and Holt D (1974): Digoxin in benign intracranial hypertension. Lancet; Mar,2,1(7853): (Letter). 11. Sussman JD, Sarkies N and Pickard JD (1988): Benign intracranial hypertension. Pseudotumour cerebri: idiopathic intracranial hypertension. Adv Tech Stand Neurosurg; 24: Rifaat M (1993): Benign intracranial hypertension: introduction of a new technique, the Rifaat`s parietal flap, Med J Cairo Univ; 61 (No. 2) : Burgett RA, Purvin VA and Kawasaki A (1997): Lumboperitoneal shunting for pseudotumor cerebri. Neurology; Sep, 49(3): Kaye AH, Galbraith JK and King J (1981): Intracranial pressure following optic nerve decompression for benign intracranial hypertension. J Neurosurg; 55 : Flaharty PM and Sergott RC (1992): Optic nerve sheath decompression. Ophthalmol Clin North Am; 5(No. 3): Sergott RC, Savino PJ and Bosly TN (1988): Modified optic nerve sheath decompression provides Long-term visual improvement for pseudotumor cerebri. Arch., Ophthalmol; 106: Plotnik JL and Kosmorsky GS (1993): Operative complications of optic nerve sheath decompression. Ophthalmology; 100:

16 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan Goh KY, Schatz NJ, Glaser JS (1997): Optic nerve sheath fenestration for pseudotumor cerebri. J Neuroophthalmol; Jun; 17(2): Wall M (2000): Idiopathic intracranial hypertension: mechanisms of visual loss and disease management. Semin Neurol; 20(1): Blanchard EB and Andrasik F (1985): Management of chronic headaches, a psychological approach. First Edition. Wheaton A., Co. Ltd., Exeter Pergamon Press. 21. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults (1998): The evidence report. National Institutes of Health. Obes Res; 6 (suppl): Kline LB and Bajandas FJ (1996): The swollen Optic Disc. In: Drummond AE and Huda CM (Eds.), Neuro-ophthalmology Review Manual. SLACK Inc. Fourth edition; chapter 9: Spoor TC and McHenry JG (1993): Long-term effectiveness of optic nerve sheath decompression for pseudotumor cerebri. Arch Ophthalmol; 111: Fishman RA (1992): Cerebrospinal Fluid in Diseases of the Nervous System. 2nd ed. Philadelphia, WB Saunders. 25. Tillman O, Kaiser HJ and Killer HE (2002): Pseudotumor cerebri in a patient with Goldenhar's and Duane's syndromes. Ophthalmologica; Jul-Aug, 216 (4): Sergott R C (1992): Optic nerve sheath decompression. Int Ophthalmol Clin; 32: Angiari P, Corradini L, Corsi M and Merli GA (1992): Pseudotumor cerebri. Lumboperitoneal shunt in long lasting cases. J Neurolosurgical Sciences; Jul-Sep; 36(3): Greer M (1963): Benign intracranial hypertension. III. Pregnancy. Neurology; 13: Huna-Baron R and Kupersmith MJ (2002): Idiopathic intracranial hypertension in pregnancy. J Neurol; Aug; 249(8): Carta A, Bertuzzi F, Cologno D, Giorgi C, Montanari E and Tedesco S (2004): Idiopathic intracranial hypertension (pseudotumor cerebri): descriptive epidemiology, clinical features, and visual outcome in Parma, Italy, 1990 to Eur J Ophthalmol; Jan-Feb;14(1): Galvin JA and Van Stavern GP (2004): Clinical characterization of idiopathic intracranial hypertension at the Detroit Medical Center. J Neurol Sci; Aug 30; 223(2): Lueck C and McIlwaine G (2005): Interventions for idiopathic intracranial hypertension. Cochrane Database Syst Rev; Jul 20;(3):CD Merle H, Smadja D, Ayeboua L, Cabre P, Gerard M, Alliot E, Rapoport P, Jallot-Sainte-Rose N, Richer R and Poman G (1998): Benign intracranial hypertension. Retrospective study of 20 cases. J Fr Ophtalmol; Jan;21(1): [ABSTRACT]. 34. Curry WT, Butler WE and Barker FG 2nd (2005): Rapidly rising incidence of cerebrospinal fluid shunting procedures for idiopathic intracranial hypertension in the United States, Neurosurgery; Jul;57(1): Digre KB and Corbett JJ (1988): Pseudotumor cerebri in men. Arch Neurol; 45: Corbett JJ, Savino PJ, and Thompson HS (1982): Visual loss in pseudotumor cerebri. Follow-up of 57 patients from 5 to 41 years and profile of 14 patients with permanent severe visual loss. Arch Neurol; 39: Wall M and White WN 2 nd (1998): Asymmetric papilloedema in idiopathic intracranial hypertension: prospective interocular comparison of sensory visual function. Invest Ophthal Vis Sci; 39: Lepore FE (1992): Unilateral and highly asymmetric papilledema in pseudotumor cerebri. Neurology; Mar, 42(3 Pt 1): Maxner CE, Freedman MI and Corbett JJ (1987): Asymmetric papilledema and visual loss in pseudotumor cerebri. Can J Neurol Sci; Nov, 14(4): Hart RG and Carlin JT (1982): Pseudotumor cerebri and facial pain. Arch Neurol; 39: Sugar O (1953): Central neurological complications of hypoparathyroidism. Arch Neurol Psychiatry; 70: Palmer RF, Searles HH and Boldrey EB (1959): Papilledema and hypoparathyroidism simulating brain tumor. J Neurosurg; 116: Radhakrishnan K, Ahlskog JE and Garrity JA (1994): Idiopathic intracranial hypertension. Mayo Clin Proc; Feb; 69(2): Corbett JJ (1995): Idiopathic intracranial hypertension. In: Kennard C (Ed.) recent advances in clinical neurology. No. 8 : Shapiro I and Shapiro SK (1980): Familial pseudotumor cerebri and the empty sella syndrome. Ann Ophthalmol; 12: Mezaal M and Saadah M (2005): Idiopathic intracranial hypertension in Dubai: nature and 106