Effect of Body Mass Index on Venous Sinus Pressures in Idiopathic Intracranial Hypertension Patients Before and After Endovascular Stenting

Effect of Body Mass Index on Venous Sinus Pressures in Idiopathic Intracranial Hypertension... Abstract BACKGROUND Elevated body mass index (BMI) has been correlated with worse outcomes after treatment for idiopathic intracranial hypertension (IIH). Venous sinus stenting (VSS) has emerged as a safe and effective treatment for a subset of patients with IIH and evidence of venous sinus stenosis. However, the association between BMI and the efficacy of VSS remains poorly characterized. OBJECTIVE To determine, in a retrospective cohort study, the effect of BMI on preoperative mean intracranial venous pressure (MVP) and post-VSS outcomes. METHODS We performed a retrospective evaluation of a prospectively collected database of patients with IIH and intracranial venous sinus stenosis who underwent VSS. Patient demographics and treatment factors, including pre- and postprocedural trans-stenosis pressure gradients, were analyzed to identify the relationship between BMI and outcomes after VSS. RESULTS Increasing BMI was significantly correlated with higher maximum MVP (P = .013) and higher trans-stenosis pressure gradient (P = .043) prior to treatment. The degrees of improvement in maximum MVP and pressure gradient after VSS were greatest for obese and morbidly obese patients (BMI > 30 kg/m2). Maximum poststent MVP, clinical outcomes, and stent-adjacent stenosis requiring retreatment after VSS were not significantly associated with BMI. CONCLUSION We provide direct evidence for a positive correlation between BMI and intracranial venous pressure in patients with IIH. VSS affords a significantly greater amelioration of intracranial venous hypertension and stenosis for IIH patients with higher BMIs. As such, obesity should not be a deterrent for the use of VSS in the management of IIH. Endovascular, Idiopathic intracranial hypertension, Intracranial stent, Outcome, Venous sinus ABBREVIATIONS ABBREVIATIONS BMI body mass index CSF cerebrospinal fluid ICP intracranial pressure IIH idiopathic intracranial hypertension MVP mean intracranial venous pressure VSS venous sinus stenting The prevalence of idiopathic intracranial hypertension (IIH) is approximately 1 per 100 000 in North America, although it may be up to 15 to 19 per 100 000 in the subgroup of overweight women aged 20 to 44 yr.1 Due to the increasing prevalence of obesity and the nonspecific nature of symptoms of elevated intracranial pressure (ICP), including pulsatile tinnitus, transient visual obscurations, and headaches, the true prevalence of IIH may be even higher than in the literature.2,3 The diagnostic criteria for IIH was originally defined by Walter Dandy in 1937.4 They were modified in 1985 and now include signs and symptoms of elevated ICP, elevated cerebrospinal fluid (CSF) opening pressure on lumbar puncture (>25 cm H2O) with normal composition of CSF, and no evidence of focal or structural etiology.5,6 IIH has long been associated with elevated body mass index (BMI), and weight loss is an effective treatment for this condition.7-9 The pathoetiology of IIH remains poorly understood, but a relationship among intra-abdominal pressure, central venous pressure, intracranial venous pressure, and ICP has been proposed. Although a positive correlation between higher BMI and increased intracranial venous pressure is logical, there is little direct evidence for the basis of this presumption. However, intracranial venous manometry is being performed with increasing frequency, due to the finding that intracranial dural venous sinus stenosis is significantly more common in patients with IIH than the general population. Therefore, a previously unavailable opportunity to describe the relationship between BMI and intracranial venous pressure has recently emerged. For patients with medically refractory IIH, case series have reported symptomatic improvement, resolution of increased ICP, and improvement in papilledema after endovascular treatment with venous sinus stenting (VSS).5,10-18 Precipitous decreases in ICP can occur in IIH patients who undergo VSS with concurrent ICP monitoring.19,20 Nevertheless, prior studies have suggested that the efficacy of VSS could be limited for obese or morbidly obese patients, in which extrinsic compression of the venous sinuses may be a risk factor for ongoing venous outflow obstruction and symptomatic recurrence after VSS.21,22 However, the effect of BMI on endovascular treatment outcomes for IIH remains poorly understood. Therefore, the aims of this retrospective cohort study are to (1) assess the correlation between BMI and mean intracranial venous pressure (MVP) in IIH patients prior to VSS and (2) determine the effect of BMI on clinical and angiographic outcomes after VSS for IIH. METHODS We performed a retrospective evaluation of a prospectively collected database of patients with IIH who underwent venous manometry at our institution. The prospective database has been maintained since February 2014, and this was reviewed on July 1, 2016. This study was approved by the local Institutional Review Board. Since this was a retrospective cohort study using deidentified patient data, no separate patient consent was sought. The modified Dandy criteria were used to diagnose IIH.6 Preoperative clinical and ophthalmologic assessments were performed in a standard manner, as outlined in a prior publication.19 Briefly, during the initial phase of our investigation, patients were admitted for placement of an intraparenchymal ICP monitor, which was maintained throughout the hospitalization, and during and after the VSS procedure. Later, patients with evidence of venous stenosis on noninvasive imaging (MRV or CTV) and evidence of elevated opening pressure on lumbar puncture underwent outpatient cerebral angiography, venography, and venous manometry under mild conscious sedation. Those with elevated maximum MVP, evidence of ≥50% stenosis of the intracranial venous sinuses with an associated pressure gradient of ≥8 mm Hg were considered for VSS. Data, including patient demographics, symptoms and signs at presentation, intraprocedural findings, and postoperative outcomes, were collected from review of medical charts and neuroimaging. In addition, patients were contacted by telephone to assess clinical outcomes. Venous Manometry and Pressure Measurements MVP is calculated from the systolic and diastolic venous pressures according to the formula MVP = (2/3) × (diastolic venous pressure) + (1/3) × (systolic venous pressure). During diagnostic and treatment procedures, each point is measured once, unless the segment (eg, superior sagittal sinus) is reaccessed from the contralateral side if measurements are equivocal. In those cases, the average of multiple MVP measurements was used. In some cases, the highest venous pressure occurred in the transverse sinus or torcula, rather than the superior sagittal sinus. We compared the highest venous pressure (which we termed “maximum MVP”) from each patient, the means of which were compared by BMI strata and other analyses as reported. VSS Procedure Our VSS procedure has been previously described in detail.19 Briefly, all patients are premedicated for 7 d with daily aspirin (325 mg) and clopidogrel (75 mg). Therapeutic Asprin Reaction Units (<551) and P2Y12 (<208) levels were assessed on the morning of the procedure, and additional aspirin and clopidogrel were administered as necessary. All VSS cases were performed under general anesthesia using high-resolution biplane digital subtraction angiography. Arterial and venous access was obtained, and a shuttle was advanced into the internal jugular vein ipsilateral to the stenosis. Intravenous heparin was administered according to a weight-based protocol and was not reversed following the procedure. Preprocedural angiography was performed, and the diagnostic catheter was then attached to a continuous heparinized drip. Stenting across the segment of venous stenosis was performed with an appropriately sized device under continuous fluoroscopic monitoring. A variety of stents were used, but primarily these were bare metal stents, including Protégé Everflex iliac (Medtronic, Dublin, Ireland), Precise nitinol carotid (Cordis, Hialeah, Florida), and Zilver biliary (Cook Medical, Bloomington, Indiana) stents. Clinical and Radiographic Follow-up Follow-up diagnostic angiography and venography with venous manometry were performed 3 mo after VSS, and annual follow-up with CTV or MRV was performed thereafter. Additional neuroimaging was performed for patients with recurrent or worsening neurological symptoms. For the assessment of clinical outcomes, patients who underwent VSS more than 3 mo prior were contacted by telephone and underwent a standardized telephone interview. Patients were stratified by BMI, as follows: normal was defined as a BMI ≤25, overweight was a BMI of 25 to 30, obese was a BMI of 30 to 40, and morbidly obese was a BMI ≥40 kg/m2. Statistical Analysis Mean and ranges are reported for continuous variable data points, and categorical values are reported as frequencies. Statistical analyses using Pearson's chi-square and Fisher's exact tests were performed for the comparison of categorical variables, and linear regression for correlation of continuous variables. For comparison of continuous variables by BMI category, an ordinary 1-way ANOVA analysis was used. Comparison of pre- and poststenting MVP and pressure gradients were performed using unpaired t-tests. Statistical significance was determined by P-values of <.05. Statistical analysis was performed using GraphPad Prism 7 (GraphPad, San Diego, California). RESULTS Patient and IIH Characteristics During the study period, 89 patients underwent angiographic workup for IIH. Of these, 50 IIH patients underwent placement of 70 intracranial venous stents, and these patients comprised the study cohort. At the initial procedure, 46 patients (92%) had a single stent placed, and 4 patients (8%) had ≥2 stents placed for multiple areas or a long segment of stenosis. Table 1 summarizes the patient and angiographic characteristics of the study cohort, stratified by BMI category. Patients were predominantly female (94%), with mean age 35.9 yr and BMI 37.9 kg/m2. The most common presenting symptoms were headache (98%), visual changes (most commonly intermittent transient visual obscurations; 86%), and pulsatile tinnitus (54%); papilledema was documented at presentation in 60% of patients. The most common location of venous sinus stenosis was the transverse-sigmoid junction (57.1%) followed by the transverse sinus (37.5%). No significant differences were found in patient characteristics, IIH presentation, or angiographic features among BMI categories. TABLE 1. Patient and Angiographic Characteristics of the Study Cohort   No. (%)a  Normal  Overweight  Obese  Morbidly obese    Pretreatment characteristics  (n = 50)  (n = 4)  (n = 8)  (n = 19)  (n = 19)  P-value  Patient characteristics           Females  47 (94.0)  3 (75)  8 (100)  17 (89.5)  19 (100)  .174   Mean age ± SD (yr)  35.9 ± 12.4  28.8 ± 22.2  40.3 ± 10.0  36.6 ± 29.5  37.7 ± 12.4  .345   Mean BMI (kg/m2)  37.9  23.5  27.5  36.6  46.4  <.0001  Presentation           Headache  49 (98.0)  4 (100)  8 (100)  18 (94.7)  19 (100)  .645   Visual changes  43 (86.0)  3 (75)  5 (62.5)  16 (84.2)  19 (100)  .065   Papilledema  30 (60.0)  1 (25)  4 (50)  12 (63.2)  13 (68.4)  .389   Pulsatile tinnitus  27 (54.0)  2 (50)  5 (62.5)  9 (47.4)  11 (57.9)  .788  Location of stenosisb            .494   Superior sagittal sinus  3 (5.4)  0  1 (9.1)  0  2 (9.1)     Transverse sinus  21 (37.5)  1 (20)  3 (27.3)  6 (31.6)  11 (50.0)     Transverse-sigmoid junction  32 (57.1)  3 (60)  7 (63.6)  13 (68.4)  9 (40.9)      No. (%)a  Normal  Overweight  Obese  Morbidly obese    Pretreatment characteristics  (n = 50)  (n = 4)  (n = 8)  (n = 19)  (n = 19)  P-value  Patient characteristics           Females  47 (94.0)  3 (75)  8 (100)  17 (89.5)  19 (100)  .174   Mean age ± SD (yr)  35.9 ± 12.4  28.8 ± 22.2  40.3 ± 10.0  36.6 ± 29.5  37.7 ± 12.4  .345   Mean BMI (kg/m2)  37.9  23.5  27.5  36.6  46.4  <.0001  Presentation           Headache  49 (98.0)  4 (100)  8 (100)  18 (94.7)  19 (100)  .645   Visual changes  43 (86.0)  3 (75)  5 (62.5)  16 (84.2)  19 (100)  .065   Papilledema  30 (60.0)  1 (25)  4 (50)  12 (63.2)  13 (68.4)  .389   Pulsatile tinnitus  27 (54.0)  2 (50)  5 (62.5)  9 (47.4)  11 (57.9)  .788  Location of stenosisb            .494   Superior sagittal sinus  3 (5.4)  0  1 (9.1)  0  2 (9.1)     Transverse sinus  21 (37.5)  1 (20)  3 (27.3)  6 (31.6)  11 (50.0)     Transverse-sigmoid junction  32 (57.1)  3 (60)  7 (63.6)  13 (68.4)  9 (40.9)    BMI = body mass index; SD = standard deviation. Bold face value indicate significant values i.e. P 0.05. aValues are numbers of patients (% of patients) unless otherwise noted. bPercentage indicates percentage of total stenoses, as 6 patients had multiple areas of stenosis. View Large Effect of BMI on Pre- and Post-Treatment Venous Pressures Linear regression analysis of all 89 patients undergoing angiographic workup for IIH revealed a significant positive correlation between BMI and baseline maximum MVP, as measured by cerebral venous manometry (Figure 1; P = .013). Table 2 summarizes the angiographic and clinical outcomes after VSS, stratified by BMI category. The maximum MVP measured prior to VSS was 25.4 mm Hg for the study cohort, but was significantly different among BMI categories; that is, higher BMI patients had significantly higher pre-VSS maximum MVPs. After VSS, the maximum MVP was 13.0 mm Hg, without any significant differences among BMI categories. The baseline maximum MVP decreased after VSS in all BMI categories, and this difference was statistically significant in the morbidly obese subgroup (Figure 2; P = .0004). The degree of reduction in maximum MVP was greater in patients with higher BMI: among normal weight patients, maximum MVP decreased by 7.3 mm Hg (35.0%), whereas among morbidly obese patients, maximum MVP decreased by 15.7 mm Hg (48.4%; Table 2). FIGURE 1. View largeDownload slide Linear regression analysis of all IIH patients with venous sinus stenosis treated with VSS demonstrates a significant positive correlation between BMI and maximum MVP (P = .013). FIGURE 1. View largeDownload slide Linear regression analysis of all IIH patients with venous sinus stenosis treated with VSS demonstrates a significant positive correlation between BMI and maximum MVP (P = .013). FIGURE 2. View largeDownload slide Bar plots showing the maximum MVPs before and after VSS, stratified by BMI category. The reductions in maximum MVP after VSS were statistically significant for the obese (P = .090) and morbidly obese (P = .0008) subgroups. *Unable to calculate P-value, since there was only 1 value at follow-up for this subgroup. FIGURE 2. View largeDownload slide Bar plots showing the maximum MVPs before and after VSS, stratified by BMI category. The reductions in maximum MVP after VSS were statistically significant for the obese (P = .090) and morbidly obese (P = .0008) subgroups. *Unable to calculate P-value, since there was only 1 value at follow-up for this subgroup. TABLE 2. Outcomes Among the Study Cohort, by Weight   Total  Normal  Overweight  Obese  Morbidly obese      (n = 50)  (n = 4)  (n = 8)  (n = 19)  (n = 19)  P-value  Maximum MVP           Prestent (mm Hg)  25.4  20.0  23.4  29.5  32.4  .047   Poststent (mm Hg)  13.0  12.7  12.9  21.7  16.7  .379  Clinical outcomesa           Headache (%)            .745    Improved  21 (67.7)  1 (100)  6 (85.7)  7 (58.3)  6 (60.0)      No change  9 (29.0)  0  1 (14.3)  4 (33.3)  4 (40.0)      Worsened  1 (3.2)  0  0  1 (8.3)  0     Visual function (%)            .222    Improved  18 (60.0)  0  5 (83.3)  5 (41.7)  7 (70.0)      No change  9 (30.0)  1 (50)  1 (16.7)  4 (33.3)  3 (30.0)      Worsened  3 (10.0)  0  0  3 (25.0)  0     Improved tinnitus (%)            .843    Improved  14 (46.7)  1 (100)  3 (57.1)  5 (41.7)  4 (40.0)      No change  15 (50.0)  0  4 (42.9)  6 (50.0)  5 (50.0)      Worsened  1 (3.3)  0  0  1 (8.3)  0    Stent-adjacent Stenosis (%)b  8 (16.0)  0 (0)  1 (12.5)  4 (21.1)  3 (15.8)  .754    Total  Normal  Overweight  Obese  Morbidly obese      (n = 50)  (n = 4)  (n = 8)  (n = 19)  (n = 19)  P-value  Maximum MVP           Prestent (mm Hg)  25.4  20.0  23.4  29.5  32.4  .047   Poststent (mm Hg)  13.0  12.7  12.9  21.7  16.7  .379  Clinical outcomesa           Headache (%)            .745    Improved  21 (67.7)  1 (100)  6 (85.7)  7 (58.3)  6 (60.0)      No change  9 (29.0)  0  1 (14.3)  4 (33.3)  4 (40.0)      Worsened  1 (3.2)  0  0  1 (8.3)  0     Visual function (%)            .222    Improved  18 (60.0)  0  5 (83.3)  5 (41.7)  7 (70.0)      No change  9 (30.0)  1 (50)  1 (16.7)  4 (33.3)  3 (30.0)      Worsened  3 (10.0)  0  0  3 (25.0)  0     Improved tinnitus (%)            .843    Improved  14 (46.7)  1 (100)  3 (57.1)  5 (41.7)  4 (40.0)      No change  15 (50.0)  0  4 (42.9)  6 (50.0)  5 (50.0)      Worsened  1 (3.3)  0  0  1 (8.3)  0    Stent-adjacent Stenosis (%)b  8 (16.0)  0 (0)  1 (12.5)  4 (21.1)  3 (15.8)  .754  MVP = mean venous pressure. Bold face value indicate significant values i.e. P 0.05. aClinical outcomes are measured as percentage of patients with preoperative complaint as follows: headache (n = 31); visual complaint (n = 30); tinnitus (n = 30). bStent-adjacent stenosis is measured as a percentage of all patients: total (n = 50); normal (n = 4); overweight (n = 8); obese (n = 19); morbidly obese (n = 19). View Large Linear regression analysis of the 89 patients who underwent angiographic workup also revealed a significant correlation between BMI and trans-stenosis pressure gradient (Figure 3; P = .043). The trans-stenosis pressure gradient decreased after VSS in all subgroups, and this difference was statistically significant in the obese and morbidly obese subgroups (Figure 4). The absolute reduction in pressure gradient was higher in the patients with higher BMI, but the percentage reduction was similar between BMI strata (84.5% reduction in the normal weight group; 82.3% reduction in the morbidly obese group). FIGURE 3. View largeDownload slide Linear regression analysis of all IIH patients with venous sinus stenosis treated with VSS demonstrates a significant positive correlation between BMI and trans-stenosis pressure gradient (P = .043). FIGURE 3. View largeDownload slide Linear regression analysis of all IIH patients with venous sinus stenosis treated with VSS demonstrates a significant positive correlation between BMI and trans-stenosis pressure gradient (P = .043). FIGURE 4. View largeDownload slide Bar plots showing the trans-stenosis pressure gradients before and after VSS, stratified by BMI category, under conscious sedation. The reductions in pressure gradient were statistically significant for the obese (P = .0003) and morbidly obese (P < .0001) subgroups. FIGURE 4. View largeDownload slide Bar plots showing the trans-stenosis pressure gradients before and after VSS, stratified by BMI category, under conscious sedation. The reductions in pressure gradient were statistically significant for the obese (P = .0003) and morbidly obese (P < .0001) subgroups. Clinical Outcomes and Stent-Adjacent Stenosis The mean angiographic follow-up duration after stenting was 6.8 mo. A total of 41 patients had at least 3 mo of follow-up after VSS, of which 32 were able to be assessed by telephone interview (Table 2). The mean clinical follow-up duration of the patients with available follow-up was 16.8 mo. The incidence of stent-adjacent stenosis (SAS) requiring additional VSS was 16.0%. The mean BMI was not significantly different between patients who developed SAS (37.5 kg/m2) compared with those who did not (37.9 kg/m2; P = .982). The reduction in trans-stenosis gradient after VSS was similar between those who developed SAS (mean poststent gradient 1.4 mm Hg) and those who did not develop SAS (mean poststent gradient 1.2 mm Hg). There was no correlation between reduction in pressure gradient and subsequent development of SAS. In addition, no significant differences were found among the different BMI categories in the incidence of SAS or in clinical outcomes. DISCUSSION The association of IIH with elevated BMI has been recognized since the earliest descriptions of the disorder in the 1930s.4,23 Weight loss is an effective treatment for the condition, although it is often challenging to maintain,7-9 and weight gain for IIH patients has been associated with increased symptomatic recurrence rates after treatment.24 Additionally, morbidly obese IIH patients have been shown to have worse visual outcomes compared to those with lower BMIs.25 Prospective cohort studies found improved outcomes, with respect to ICP, papilledema, and headache, after intervention with a low-calorie diet.26,27 Even weight loss of 5% to 10% total body weight appears sufficient to improve neurological symptoms and papilledema.27-29 In our analysis of a single-center cohort of IIH patients who underwent intracranial venous pressure manometry, we found a significantly positive correlation between BMI and maximum MVP. Although we are unable to establish causality, our results lend credence to the purported effect of obesity on elevated intracranial venous pressures. In part, this may be due to a central venous phenomenon, whereby central obesity causes increased intra-abdominal pressure, secondarily increasing pleural and cardiac filling pressures, and thereby impeding cerebral venous return.30 We also found that IIH patients with larger BMIs had higher trans-stenosis pressure gradients. This may be explained by the Starling-like resistor characteristics of compressible transverse or sigmoid sinuses. Using the Starling resistor model, the venous pressure differential may be significantly influenced by an external compressive force produced by parenchymal or CSF pressure fluctuations.31,32 Over the past decade, VSS has emerged as a safe and effective treatment for patients with IIH, demonstrable venous stenosis, and a trans-stenosis pressure gradient.33,34 A systematic review reported improvements in vision and headache in approximately 85% and 80% of IIH patients treated with VSS, respectively.33,35 Although the pathophysiologic mechanism of IIH in patients with venous sinus stenosis remains incompletely understood,36-38 VSS may help decrease global venous congestion within the brain parenchyma,19,39 thereby reducing intracranial blood volume and reducing ICP. We have observed that, in some cases of IIH, contrast transit time substantially decreases after VSS, which supports this theory. Alternatively, Ahmed et al31 proposed that a Starling-like resistor property of a compressible transverse or sigmoid sinus is a central component of IIH pathogenesis. External compression of venous sinuses raises venous pressure gradients and MVP, leading to decreased CSF absorption. In turn, increased CSF pressure further compresses collapsible venous sinuses, thereby exacerbating the elevated pressure gradients and MVP in a positive feedback mechanism. After VSS, the greater reduction of MVP in IIH patients with larger BMIs supports the critical role of transverse or sigmoid sinus stenosis in this proposed venous-CSF pressure feedback cycle.31,32 On the other hand, we most often observed a focal stenosis at the distal transverse sinus or transverse-sigmoid junction, rather than a long-segment stenosis in the affected sinus. In these cases, it may be that an anatomically large arachnoid granulation exacerbates impaired venous drainage due to high venous pressures, causing stenosis through a combination of the factors described above.40 This is then mechanistically corrected by VSS. Treatments for IIH, including VSS, have been suggested to be less effective for patients with the largest BMIs.21,22 Additionally, there is a theoretically heightened risk of SAS in obese patients, which could lead to higher VSS failure rates.34 We found that, rather than being less effective for patients with the highest BMI, these patients had similar clinical outcomes and rates of SAS compared with lower BMI strata in our cohort. Additionally, maximum MVP, which was significantly higher in patients with the largest BMI prior to VSS, was normalized after endovascular treatment, irrespective of BMI. The rates of clinical improvement and SAS requiring retreatment were not significantly different among the various BMI categories. Limitations This study is limited by its retrospective design, although our center's VSS data are prospectively maintained. The study was performed at a single institution, and is therefore limited by the selection, referral, and management biases of the treating physicians. Additionally, it is unknown if our findings are generalizable to all IIH patients, particularly those without radiological evidence of venous sinus stenosis. In our cohort, there were only 4 patients with normal BMI, which makes comparison between this and other weight strata more challenging. The assessment of weight was made for each patient at the initial visit and was not remeasured at follow-up, so there is a possibility that patient weight classes changed after stenting, which may have confounded assessment of outcomes. Finally, the assessment of clinical outcomes was performed in a nonblinded manner, via a telephone survey. Although this was performed using a structured questionnaire (Figure, Supplemental Digital Content), the assessment of outcomes may be affected by recall bias and incomplete follow-up. Further studies are needed to better define the role of obesity in the pathophysiology of IIH and its effect on treatment outcomes for the subset of affected patients who are refractory to medical therapy. CONCLUSION Our study provides direct evidence for the association of increasing BMI with greater maximum MVP and trans-stenosis pressure gradient for IIH patients with venous sinus stenosis. The efficacy of VSS does not appear to be diminished by obesity. In fact, VSS affords greater reductions in maximum MVP and trans-stenosis pressure gradient for patients with higher BMIs. Future prospective comparisons of VSS with surgical interventions for medically refractory IIH, with assessment of long-term outcomes, will help elucidate the role of endovascular therapy in the management of this condition. Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Durcan FJ, Corbett JJ, Wall M. The incidence of pseudotumor cerebri. Population studies in Iowa and Louisiana. Arch Neurol . 1988; 45 (8): 875 -877. Google Scholar CrossRef Search ADS PubMed  2. Raoof N, Sharrack B, Pepper IM, Hickman SJ. The incidence and prevalence of idiopathic intracranial hypertension in Sheffield, UK. Eur J Neurol.  2011; 18 (10): 1266- 1268. Google Scholar CrossRef Search ADS PubMed  3. Hamdalla IN, Shamseddeen HN, Zelada Getty JL, Smith W, Ali AR. Greater than expected prevalence of pseudotumor cerebri: a prospective study. Surg Obes Rel Dis.  2013; 9 (1): 77- 82. 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Goodwin CR, Elder BD, Ward A et al.   Risk factors for failed transverse sinus stenting in pseudotumor cerebri patients. Clin Neurol Neurosurg . 2014; 127: 75- 78. Google Scholar CrossRef Search ADS PubMed  22. Xu K, Yu T, Yuan Y, Yu J. Current status of the application of intracranial venous sinus stenting. Int J Med Sci.  2015; 12 (10): 780- 789. Google Scholar CrossRef Search ADS PubMed  23. Daniels AB, Liu GT, Volpe NJ et al.   Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol.  2007; 143 (4): 635- 641. Google Scholar CrossRef Search ADS PubMed  24. Ko MW, Chang SC, Ridha MA et al.   Weight gain and recurrence in idiopathic intracranial hypertension: a case-control study. Neurology.  2011; 76 (18): 1564- 1567. Google Scholar CrossRef Search ADS PubMed  25. Szewka AJ, Bruce BB, Newman NJ, Biousse V. Idiopathic intracranial hypertension: relation between obesity and visual outcomes. J Neuroophthalmol.  2013; 33 (1): 4- 8. Google Scholar CrossRef Search ADS PubMed  26. Slair AJ, Burdon MA, Nightingale PG et al.   Low energy diet and intracranial pressure in women with idiopathic intracranial hypertension: prospective cohort study. BMJ.  2010; 341, doi: 10.1136/bmj.c2701. 27. Newborg B. Pseudotumor cerebri treated by rice reduction diet. Arch Intern Med.  1974; 133 (5): 802- 807. Google Scholar CrossRef Search ADS PubMed  28. Jonson LN, Krohel GB, Madsen RW, March Jr GA. The role of weight loss and acetazolamide in the treatment of idiopathic intracranial hypertension (pseudotumor cerebri). Ophthalmology.  1998; 105 (12): 2313- 2317. Google Scholar CrossRef Search ADS PubMed  29. Wong R, Madill SA, Pandey P, Riordan-Eva P. Idiopathic intracranial hypertension: the association between weight loss and the requirement for systemic treatment. BMC Ophthalmol.  2007; 7: 15. Google Scholar CrossRef Search ADS PubMed  30. Sugerman JH, DeMaria EJ, Felton, 3rd WL, Nakatsuka M, Sismanis A. Increased intra-abdominal pressure and cardiac filling pressures in obesity-associated pseudotumor cerebri. Neurology.  1997; 49 (2): 507- 511. Google Scholar CrossRef Search ADS PubMed  31. Ahmed RM, Wilkinson M, Parker GD et al.   Transverse sinus stenting for idiopathic intracranial hypertension: a review of 52 patients and of model predictions. AJNR Am J Neuroradiol.  2011; 32 (8): 1408- 1414. Google Scholar CrossRef Search ADS PubMed  32. De Simone R, Ranieri A, Bonavita V. Starling resistors, autoregulation of cerebral perfusion and the pathogenesis of idiopathic intracranial hypertension. Panminerva Med.  2017;59(1):76-89. 33. Teleb MS, Cziep ME, Issa M et al.   Stenting and angioplasty for idiopathic intracranial hypertension: a case series with clinical, angiographic, ophthalmological, complication, and pressure reporting. J Neuroimaging.  2015; 25 (1): 72- 80. Google Scholar CrossRef Search ADS PubMed  34. Starke RM, Wang T, Ding D et al.   Endovascular treatment of venous sinus stenosis in idiopathic intracranial hypertension: complications, neurological outcomes, and radiographic results. Sci World J.  2015; 2015: 140408, doi: 10.1155/2015/140408. 35. King JO, Mitchell PJ, Thomson KR, Tress BM. Cerebral venography and manometry in idiopathic intracranial hypertension. Neurology.  1995; 45 (12): 2224- 2228. Google Scholar CrossRef Search ADS PubMed  36. Bono F, Lupo MR, Lavano A et al.   Cerebral MR. venography of transverse sinuses in subjects with normal CSF pressure. Neurology.  2003; 61 (9): 1267- 1270. Google Scholar CrossRef Search ADS PubMed  37. McGeeney BE, Friedman DI. Pseudotumor cerebri pathophysiology. Headache.  2014; 54 (3): 445- 458. Google Scholar CrossRef Search ADS PubMed  38. Lai LT, Danesh-Meyer HV, Kaye AH. Visual outcomes and headache following interventions for idiopathic intracranial hypertension. J Clin Neurosci.  2014; 21 (10): 1670- 1678. Google Scholar CrossRef Search ADS PubMed  39. Bono F, Quattrone A. Clinical course of idiopathic intracranial hypertension with transverse sinus stenosis. Neurology.  2013; 81 (7): 695. Google Scholar CrossRef Search ADS PubMed  40. Batra R, Sinclair A. Idiopathic intracranial hypertension; research progress and emerging therapies. J Neurol.  2014; 261 (3): 451- 460. Google Scholar CrossRef Search ADS PubMed  Supplemental digital content is available for this article at www.neurosurgery-online.com. Copyright © 2017 by the Congress of Neurological Surgeons http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Effect of Body Mass Index on Venous Sinus Pressures in Idiopathic Intracranial Hypertension Patients Before and After Endovascular Stenting

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Abstract

Abstract BACKGROUND Elevated body mass index (BMI) has been correlated with worse outcomes after treatment for idiopathic intracranial hypertension (IIH). Venous sinus stenting (VSS) has emerged as a safe and effective treatment for a subset of patients with IIH and evidence of venous sinus stenosis. However, the association between BMI and the efficacy of VSS remains poorly characterized. OBJECTIVE To determine, in a retrospective cohort study, the effect of BMI on preoperative mean intracranial venous pressure (MVP) and post-VSS outcomes. METHODS We performed a retrospective evaluation of a prospectively collected database of patients with IIH and intracranial venous sinus stenosis who underwent VSS. Patient demographics and treatment factors, including pre- and postprocedural trans-stenosis pressure gradients, were analyzed to identify the relationship between BMI and outcomes after VSS. RESULTS Increasing BMI was significantly correlated with higher maximum MVP (P = .013) and higher trans-stenosis pressure gradient (P = .043) prior to treatment. The degrees of improvement in maximum MVP and pressure gradient after VSS were greatest for obese and morbidly obese patients (BMI > 30 kg/m2). Maximum poststent MVP, clinical outcomes, and stent-adjacent stenosis requiring retreatment after VSS were not significantly associated with BMI. CONCLUSION We provide direct evidence for a positive correlation between BMI and intracranial venous pressure in patients with IIH. VSS affords a significantly greater amelioration of intracranial venous hypertension and stenosis for IIH patients with higher BMIs. As such, obesity should not be a deterrent for the use of VSS in the management of IIH. Endovascular, Idiopathic intracranial hypertension, Intracranial stent, Outcome, Venous sinus ABBREVIATIONS ABBREVIATIONS BMI body mass index CSF cerebrospinal fluid ICP intracranial pressure IIH idiopathic intracranial hypertension MVP mean intracranial venous pressure VSS venous sinus stenting The prevalence of idiopathic intracranial hypertension (IIH) is approximately 1 per 100 000 in North America, although it may be up to 15 to 19 per 100 000 in the subgroup of overweight women aged 20 to 44 yr.1 Due to the increasing prevalence of obesity and the nonspecific nature of symptoms of elevated intracranial pressure (ICP), including pulsatile tinnitus, transient visual obscurations, and headaches, the true prevalence of IIH may be even higher than in the literature.2,3 The diagnostic criteria for IIH was originally defined by Walter Dandy in 1937.4 They were modified in 1985 and now include signs and symptoms of elevated ICP, elevated cerebrospinal fluid (CSF) opening pressure on lumbar puncture (>25 cm H2O) with normal composition of CSF, and no evidence of focal or structural etiology.5,6 IIH has long been associated with elevated body mass index (BMI), and weight loss is an effective treatment for this condition.7-9 The pathoetiology of IIH remains poorly understood, but a relationship among intra-abdominal pressure, central venous pressure, intracranial venous pressure, and ICP has been proposed. Although a positive correlation between higher BMI and increased intracranial venous pressure is logical, there is little direct evidence for the basis of this presumption. However, intracranial venous manometry is being performed with increasing frequency, due to the finding that intracranial dural venous sinus stenosis is significantly more common in patients with IIH than the general population. Therefore, a previously unavailable opportunity to describe the relationship between BMI and intracranial venous pressure has recently emerged. For patients with medically refractory IIH, case series have reported symptomatic improvement, resolution of increased ICP, and improvement in papilledema after endovascular treatment with venous sinus stenting (VSS).5,10-18 Precipitous decreases in ICP can occur in IIH patients who undergo VSS with concurrent ICP monitoring.19,20 Nevertheless, prior studies have suggested that the efficacy of VSS could be limited for obese or morbidly obese patients, in which extrinsic compression of the venous sinuses may be a risk factor for ongoing venous outflow obstruction and symptomatic recurrence after VSS.21,22 However, the effect of BMI on endovascular treatment outcomes for IIH remains poorly understood. Therefore, the aims of this retrospective cohort study are to (1) assess the correlation between BMI and mean intracranial venous pressure (MVP) in IIH patients prior to VSS and (2) determine the effect of BMI on clinical and angiographic outcomes after VSS for IIH. METHODS We performed a retrospective evaluation of a prospectively collected database of patients with IIH who underwent venous manometry at our institution. The prospective database has been maintained since February 2014, and this was reviewed on July 1, 2016. This study was approved by the local Institutional Review Board. Since this was a retrospective cohort study using deidentified patient data, no separate patient consent was sought. The modified Dandy criteria were used to diagnose IIH.6 Preoperative clinical and ophthalmologic assessments were performed in a standard manner, as outlined in a prior publication.19 Briefly, during the initial phase of our investigation, patients were admitted for placement of an intraparenchymal ICP monitor, which was maintained throughout the hospitalization, and during and after the VSS procedure. Later, patients with evidence of venous stenosis on noninvasive imaging (MRV or CTV) and evidence of elevated opening pressure on lumbar puncture underwent outpatient cerebral angiography, venography, and venous manometry under mild conscious sedation. Those with elevated maximum MVP, evidence of ≥50% stenosis of the intracranial venous sinuses with an associated pressure gradient of ≥8 mm Hg were considered for VSS. Data, including patient demographics, symptoms and signs at presentation, intraprocedural findings, and postoperative outcomes, were collected from review of medical charts and neuroimaging. In addition, patients were contacted by telephone to assess clinical outcomes. Venous Manometry and Pressure Measurements MVP is calculated from the systolic and diastolic venous pressures according to the formula MVP = (2/3) × (diastolic venous pressure) + (1/3) × (systolic venous pressure). During diagnostic and treatment procedures, each point is measured once, unless the segment (eg, superior sagittal sinus) is reaccessed from the contralateral side if measurements are equivocal. In those cases, the average of multiple MVP measurements was used. In some cases, the highest venous pressure occurred in the transverse sinus or torcula, rather than the superior sagittal sinus. We compared the highest venous pressure (which we termed “maximum MVP”) from each patient, the means of which were compared by BMI strata and other analyses as reported. VSS Procedure Our VSS procedure has been previously described in detail.19 Briefly, all patients are premedicated for 7 d with daily aspirin (325 mg) and clopidogrel (75 mg). Therapeutic Asprin Reaction Units (<551) and P2Y12 (<208) levels were assessed on the morning of the procedure, and additional aspirin and clopidogrel were administered as necessary. All VSS cases were performed under general anesthesia using high-resolution biplane digital subtraction angiography. Arterial and venous access was obtained, and a shuttle was advanced into the internal jugular vein ipsilateral to the stenosis. Intravenous heparin was administered according to a weight-based protocol and was not reversed following the procedure. Preprocedural angiography was performed, and the diagnostic catheter was then attached to a continuous heparinized drip. Stenting across the segment of venous stenosis was performed with an appropriately sized device under continuous fluoroscopic monitoring. A variety of stents were used, but primarily these were bare metal stents, including Protégé Everflex iliac (Medtronic, Dublin, Ireland), Precise nitinol carotid (Cordis, Hialeah, Florida), and Zilver biliary (Cook Medical, Bloomington, Indiana) stents. Clinical and Radiographic Follow-up Follow-up diagnostic angiography and venography with venous manometry were performed 3 mo after VSS, and annual follow-up with CTV or MRV was performed thereafter. Additional neuroimaging was performed for patients with recurrent or worsening neurological symptoms. For the assessment of clinical outcomes, patients who underwent VSS more than 3 mo prior were contacted by telephone and underwent a standardized telephone interview. Patients were stratified by BMI, as follows: normal was defined as a BMI ≤25, overweight was a BMI of 25 to 30, obese was a BMI of 30 to 40, and morbidly obese was a BMI ≥40 kg/m2. Statistical Analysis Mean and ranges are reported for continuous variable data points, and categorical values are reported as frequencies. Statistical analyses using Pearson's chi-square and Fisher's exact tests were performed for the comparison of categorical variables, and linear regression for correlation of continuous variables. For comparison of continuous variables by BMI category, an ordinary 1-way ANOVA analysis was used. Comparison of pre- and poststenting MVP and pressure gradients were performed using unpaired t-tests. Statistical significance was determined by P-values of <.05. Statistical analysis was performed using GraphPad Prism 7 (GraphPad, San Diego, California). RESULTS Patient and IIH Characteristics During the study period, 89 patients underwent angiographic workup for IIH. Of these, 50 IIH patients underwent placement of 70 intracranial venous stents, and these patients comprised the study cohort. At the initial procedure, 46 patients (92%) had a single stent placed, and 4 patients (8%) had ≥2 stents placed for multiple areas or a long segment of stenosis. Table 1 summarizes the patient and angiographic characteristics of the study cohort, stratified by BMI category. Patients were predominantly female (94%), with mean age 35.9 yr and BMI 37.9 kg/m2. The most common presenting symptoms were headache (98%), visual changes (most commonly intermittent transient visual obscurations; 86%), and pulsatile tinnitus (54%); papilledema was documented at presentation in 60% of patients. The most common location of venous sinus stenosis was the transverse-sigmoid junction (57.1%) followed by the transverse sinus (37.5%). No significant differences were found in patient characteristics, IIH presentation, or angiographic features among BMI categories. TABLE 1. Patient and Angiographic Characteristics of the Study Cohort   No. (%)a  Normal  Overweight  Obese  Morbidly obese    Pretreatment characteristics  (n = 50)  (n = 4)  (n = 8)  (n = 19)  (n = 19)  P-value  Patient characteristics           Females  47 (94.0)  3 (75)  8 (100)  17 (89.5)  19 (100)  .174   Mean age ± SD (yr)  35.9 ± 12.4  28.8 ± 22.2  40.3 ± 10.0  36.6 ± 29.5  37.7 ± 12.4  .345   Mean BMI (kg/m2)  37.9  23.5  27.5  36.6  46.4  <.0001  Presentation           Headache  49 (98.0)  4 (100)  8 (100)  18 (94.7)  19 (100)  .645   Visual changes  43 (86.0)  3 (75)  5 (62.5)  16 (84.2)  19 (100)  .065   Papilledema  30 (60.0)  1 (25)  4 (50)  12 (63.2)  13 (68.4)  .389   Pulsatile tinnitus  27 (54.0)  2 (50)  5 (62.5)  9 (47.4)  11 (57.9)  .788  Location of stenosisb            .494   Superior sagittal sinus  3 (5.4)  0  1 (9.1)  0  2 (9.1)     Transverse sinus  21 (37.5)  1 (20)  3 (27.3)  6 (31.6)  11 (50.0)     Transverse-sigmoid junction  32 (57.1)  3 (60)  7 (63.6)  13 (68.4)  9 (40.9)      No. (%)a  Normal  Overweight  Obese  Morbidly obese    Pretreatment characteristics  (n = 50)  (n = 4)  (n = 8)  (n = 19)  (n = 19)  P-value  Patient characteristics           Females  47 (94.0)  3 (75)  8 (100)  17 (89.5)  19 (100)  .174   Mean age ± SD (yr)  35.9 ± 12.4  28.8 ± 22.2  40.3 ± 10.0  36.6 ± 29.5  37.7 ± 12.4  .345   Mean BMI (kg/m2)  37.9  23.5  27.5  36.6  46.4  <.0001  Presentation           Headache  49 (98.0)  4 (100)  8 (100)  18 (94.7)  19 (100)  .645   Visual changes  43 (86.0)  3 (75)  5 (62.5)  16 (84.2)  19 (100)  .065   Papilledema  30 (60.0)  1 (25)  4 (50)  12 (63.2)  13 (68.4)  .389   Pulsatile tinnitus  27 (54.0)  2 (50)  5 (62.5)  9 (47.4)  11 (57.9)  .788  Location of stenosisb            .494   Superior sagittal sinus  3 (5.4)  0  1 (9.1)  0  2 (9.1)     Transverse sinus  21 (37.5)  1 (20)  3 (27.3)  6 (31.6)  11 (50.0)     Transverse-sigmoid junction  32 (57.1)  3 (60)  7 (63.6)  13 (68.4)  9 (40.9)    BMI = body mass index; SD = standard deviation. Bold face value indicate significant values i.e. P 0.05. aValues are numbers of patients (% of patients) unless otherwise noted. bPercentage indicates percentage of total stenoses, as 6 patients had multiple areas of stenosis. View Large Effect of BMI on Pre- and Post-Treatment Venous Pressures Linear regression analysis of all 89 patients undergoing angiographic workup for IIH revealed a significant positive correlation between BMI and baseline maximum MVP, as measured by cerebral venous manometry (Figure 1; P = .013). Table 2 summarizes the angiographic and clinical outcomes after VSS, stratified by BMI category. The maximum MVP measured prior to VSS was 25.4 mm Hg for the study cohort, but was significantly different among BMI categories; that is, higher BMI patients had significantly higher pre-VSS maximum MVPs. After VSS, the maximum MVP was 13.0 mm Hg, without any significant differences among BMI categories. The baseline maximum MVP decreased after VSS in all BMI categories, and this difference was statistically significant in the morbidly obese subgroup (Figure 2; P = .0004). The degree of reduction in maximum MVP was greater in patients with higher BMI: among normal weight patients, maximum MVP decreased by 7.3 mm Hg (35.0%), whereas among morbidly obese patients, maximum MVP decreased by 15.7 mm Hg (48.4%; Table 2). FIGURE 1. View largeDownload slide Linear regression analysis of all IIH patients with venous sinus stenosis treated with VSS demonstrates a significant positive correlation between BMI and maximum MVP (P = .013). FIGURE 1. View largeDownload slide Linear regression analysis of all IIH patients with venous sinus stenosis treated with VSS demonstrates a significant positive correlation between BMI and maximum MVP (P = .013). FIGURE 2. View largeDownload slide Bar plots showing the maximum MVPs before and after VSS, stratified by BMI category. The reductions in maximum MVP after VSS were statistically significant for the obese (P = .090) and morbidly obese (P = .0008) subgroups. *Unable to calculate P-value, since there was only 1 value at follow-up for this subgroup. FIGURE 2. View largeDownload slide Bar plots showing the maximum MVPs before and after VSS, stratified by BMI category. The reductions in maximum MVP after VSS were statistically significant for the obese (P = .090) and morbidly obese (P = .0008) subgroups. *Unable to calculate P-value, since there was only 1 value at follow-up for this subgroup. TABLE 2. Outcomes Among the Study Cohort, by Weight   Total  Normal  Overweight  Obese  Morbidly obese      (n = 50)  (n = 4)  (n = 8)  (n = 19)  (n = 19)  P-value  Maximum MVP           Prestent (mm Hg)  25.4  20.0  23.4  29.5  32.4  .047   Poststent (mm Hg)  13.0  12.7  12.9  21.7  16.7  .379  Clinical outcomesa           Headache (%)            .745    Improved  21 (67.7)  1 (100)  6 (85.7)  7 (58.3)  6 (60.0)      No change  9 (29.0)  0  1 (14.3)  4 (33.3)  4 (40.0)      Worsened  1 (3.2)  0  0  1 (8.3)  0     Visual function (%)            .222    Improved  18 (60.0)  0  5 (83.3)  5 (41.7)  7 (70.0)      No change  9 (30.0)  1 (50)  1 (16.7)  4 (33.3)  3 (30.0)      Worsened  3 (10.0)  0  0  3 (25.0)  0     Improved tinnitus (%)            .843    Improved  14 (46.7)  1 (100)  3 (57.1)  5 (41.7)  4 (40.0)      No change  15 (50.0)  0  4 (42.9)  6 (50.0)  5 (50.0)      Worsened  1 (3.3)  0  0  1 (8.3)  0    Stent-adjacent Stenosis (%)b  8 (16.0)  0 (0)  1 (12.5)  4 (21.1)  3 (15.8)  .754    Total  Normal  Overweight  Obese  Morbidly obese      (n = 50)  (n = 4)  (n = 8)  (n = 19)  (n = 19)  P-value  Maximum MVP           Prestent (mm Hg)  25.4  20.0  23.4  29.5  32.4  .047   Poststent (mm Hg)  13.0  12.7  12.9  21.7  16.7  .379  Clinical outcomesa           Headache (%)            .745    Improved  21 (67.7)  1 (100)  6 (85.7)  7 (58.3)  6 (60.0)      No change  9 (29.0)  0  1 (14.3)  4 (33.3)  4 (40.0)      Worsened  1 (3.2)  0  0  1 (8.3)  0     Visual function (%)            .222    Improved  18 (60.0)  0  5 (83.3)  5 (41.7)  7 (70.0)      No change  9 (30.0)  1 (50)  1 (16.7)  4 (33.3)  3 (30.0)      Worsened  3 (10.0)  0  0  3 (25.0)  0     Improved tinnitus (%)            .843    Improved  14 (46.7)  1 (100)  3 (57.1)  5 (41.7)  4 (40.0)      No change  15 (50.0)  0  4 (42.9)  6 (50.0)  5 (50.0)      Worsened  1 (3.3)  0  0  1 (8.3)  0    Stent-adjacent Stenosis (%)b  8 (16.0)  0 (0)  1 (12.5)  4 (21.1)  3 (15.8)  .754  MVP = mean venous pressure. Bold face value indicate significant values i.e. P 0.05. aClinical outcomes are measured as percentage of patients with preoperative complaint as follows: headache (n = 31); visual complaint (n = 30); tinnitus (n = 30). bStent-adjacent stenosis is measured as a percentage of all patients: total (n = 50); normal (n = 4); overweight (n = 8); obese (n = 19); morbidly obese (n = 19). View Large Linear regression analysis of the 89 patients who underwent angiographic workup also revealed a significant correlation between BMI and trans-stenosis pressure gradient (Figure 3; P = .043). The trans-stenosis pressure gradient decreased after VSS in all subgroups, and this difference was statistically significant in the obese and morbidly obese subgroups (Figure 4). The absolute reduction in pressure gradient was higher in the patients with higher BMI, but the percentage reduction was similar between BMI strata (84.5% reduction in the normal weight group; 82.3% reduction in the morbidly obese group). FIGURE 3. View largeDownload slide Linear regression analysis of all IIH patients with venous sinus stenosis treated with VSS demonstrates a significant positive correlation between BMI and trans-stenosis pressure gradient (P = .043). FIGURE 3. View largeDownload slide Linear regression analysis of all IIH patients with venous sinus stenosis treated with VSS demonstrates a significant positive correlation between BMI and trans-stenosis pressure gradient (P = .043). FIGURE 4. View largeDownload slide Bar plots showing the trans-stenosis pressure gradients before and after VSS, stratified by BMI category, under conscious sedation. The reductions in pressure gradient were statistically significant for the obese (P = .0003) and morbidly obese (P < .0001) subgroups. FIGURE 4. View largeDownload slide Bar plots showing the trans-stenosis pressure gradients before and after VSS, stratified by BMI category, under conscious sedation. The reductions in pressure gradient were statistically significant for the obese (P = .0003) and morbidly obese (P < .0001) subgroups. Clinical Outcomes and Stent-Adjacent Stenosis The mean angiographic follow-up duration after stenting was 6.8 mo. A total of 41 patients had at least 3 mo of follow-up after VSS, of which 32 were able to be assessed by telephone interview (Table 2). The mean clinical follow-up duration of the patients with available follow-up was 16.8 mo. The incidence of stent-adjacent stenosis (SAS) requiring additional VSS was 16.0%. The mean BMI was not significantly different between patients who developed SAS (37.5 kg/m2) compared with those who did not (37.9 kg/m2; P = .982). The reduction in trans-stenosis gradient after VSS was similar between those who developed SAS (mean poststent gradient 1.4 mm Hg) and those who did not develop SAS (mean poststent gradient 1.2 mm Hg). There was no correlation between reduction in pressure gradient and subsequent development of SAS. In addition, no significant differences were found among the different BMI categories in the incidence of SAS or in clinical outcomes. DISCUSSION The association of IIH with elevated BMI has been recognized since the earliest descriptions of the disorder in the 1930s.4,23 Weight loss is an effective treatment for the condition, although it is often challenging to maintain,7-9 and weight gain for IIH patients has been associated with increased symptomatic recurrence rates after treatment.24 Additionally, morbidly obese IIH patients have been shown to have worse visual outcomes compared to those with lower BMIs.25 Prospective cohort studies found improved outcomes, with respect to ICP, papilledema, and headache, after intervention with a low-calorie diet.26,27 Even weight loss of 5% to 10% total body weight appears sufficient to improve neurological symptoms and papilledema.27-29 In our analysis of a single-center cohort of IIH patients who underwent intracranial venous pressure manometry, we found a significantly positive correlation between BMI and maximum MVP. Although we are unable to establish causality, our results lend credence to the purported effect of obesity on elevated intracranial venous pressures. In part, this may be due to a central venous phenomenon, whereby central obesity causes increased intra-abdominal pressure, secondarily increasing pleural and cardiac filling pressures, and thereby impeding cerebral venous return.30 We also found that IIH patients with larger BMIs had higher trans-stenosis pressure gradients. This may be explained by the Starling-like resistor characteristics of compressible transverse or sigmoid sinuses. Using the Starling resistor model, the venous pressure differential may be significantly influenced by an external compressive force produced by parenchymal or CSF pressure fluctuations.31,32 Over the past decade, VSS has emerged as a safe and effective treatment for patients with IIH, demonstrable venous stenosis, and a trans-stenosis pressure gradient.33,34 A systematic review reported improvements in vision and headache in approximately 85% and 80% of IIH patients treated with VSS, respectively.33,35 Although the pathophysiologic mechanism of IIH in patients with venous sinus stenosis remains incompletely understood,36-38 VSS may help decrease global venous congestion within the brain parenchyma,19,39 thereby reducing intracranial blood volume and reducing ICP. We have observed that, in some cases of IIH, contrast transit time substantially decreases after VSS, which supports this theory. Alternatively, Ahmed et al31 proposed that a Starling-like resistor property of a compressible transverse or sigmoid sinus is a central component of IIH pathogenesis. External compression of venous sinuses raises venous pressure gradients and MVP, leading to decreased CSF absorption. In turn, increased CSF pressure further compresses collapsible venous sinuses, thereby exacerbating the elevated pressure gradients and MVP in a positive feedback mechanism. After VSS, the greater reduction of MVP in IIH patients with larger BMIs supports the critical role of transverse or sigmoid sinus stenosis in this proposed venous-CSF pressure feedback cycle.31,32 On the other hand, we most often observed a focal stenosis at the distal transverse sinus or transverse-sigmoid junction, rather than a long-segment stenosis in the affected sinus. In these cases, it may be that an anatomically large arachnoid granulation exacerbates impaired venous drainage due to high venous pressures, causing stenosis through a combination of the factors described above.40 This is then mechanistically corrected by VSS. Treatments for IIH, including VSS, have been suggested to be less effective for patients with the largest BMIs.21,22 Additionally, there is a theoretically heightened risk of SAS in obese patients, which could lead to higher VSS failure rates.34 We found that, rather than being less effective for patients with the highest BMI, these patients had similar clinical outcomes and rates of SAS compared with lower BMI strata in our cohort. Additionally, maximum MVP, which was significantly higher in patients with the largest BMI prior to VSS, was normalized after endovascular treatment, irrespective of BMI. The rates of clinical improvement and SAS requiring retreatment were not significantly different among the various BMI categories. Limitations This study is limited by its retrospective design, although our center's VSS data are prospectively maintained. The study was performed at a single institution, and is therefore limited by the selection, referral, and management biases of the treating physicians. Additionally, it is unknown if our findings are generalizable to all IIH patients, particularly those without radiological evidence of venous sinus stenosis. In our cohort, there were only 4 patients with normal BMI, which makes comparison between this and other weight strata more challenging. The assessment of weight was made for each patient at the initial visit and was not remeasured at follow-up, so there is a possibility that patient weight classes changed after stenting, which may have confounded assessment of outcomes. Finally, the assessment of clinical outcomes was performed in a nonblinded manner, via a telephone survey. Although this was performed using a structured questionnaire (Figure, Supplemental Digital Content), the assessment of outcomes may be affected by recall bias and incomplete follow-up. Further studies are needed to better define the role of obesity in the pathophysiology of IIH and its effect on treatment outcomes for the subset of affected patients who are refractory to medical therapy. CONCLUSION Our study provides direct evidence for the association of increasing BMI with greater maximum MVP and trans-stenosis pressure gradient for IIH patients with venous sinus stenosis. The efficacy of VSS does not appear to be diminished by obesity. In fact, VSS affords greater reductions in maximum MVP and trans-stenosis pressure gradient for patients with higher BMIs. 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NeurosurgeryOxford University Press

Published: Apr 1, 2018

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