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Update on Idiopathic Intracranial Hypertension Management

Atualização no manejo da Hipertensão Intracraniana Idiopática

ABSTRACT

Background:

Idiopathic Intracranial Hypertension (IIH) is a secondary headache with a steadily growing incidence. Currently, there is little evidence to guide the treatment of IIH.

Objective:

To review the pathophysiology of IIH, with focus on the role of obesity as a risk factor, and the implications for new therapeutic perspectives.

Methods:

in this narrative review, we summarized the current knowledge on treatment options highlighting available evidence for managing intracranial hypertension, obesity, and headache.

Results:

Clinical Presentation: headache is the most common symptom and a significant cause of quality-of-life impairment. Visual loss is common in the diagnosis. Pathophysiology: there is no unified theory able to explain all symptoms and the evolution of the disease. There is growing data pointing to metabolic changes and obesity with a central role in IIH pathophysiology. Treatment: most published data on IIH treatment is related to pressure control and protection from visual loss. Acetazolamide and cerebrospinal fluid diversion are the best options available. Optic nerve sheath fenestration might be useful to temporally control the pressure over the optic nerve and thus protect from visual deterioration. Recently, venous sinus stenting has proven to be a safe option in selected cases. Finally, bariatric surgery has proven to effectively control elevated intracranial pressure.

Conclusion:

IIH is a potential cause of high disability. Early recognition is important, and treatment should be tailored to the needs of each case. There is a lack of research on headache management, which might persist after ICP control.

Keywords:
Pseudotumor Cerebri; Acetazolamide; Optic Nerve; Cerebrospinal Fluid; Bariatric Surgery.

RESUMO

Antecedentes:

A Hipertensão Intracraniana Idiopática (HII) é uma cefaleia secundária com incidência crescente. Atualmente há pouca evidência disponível na literatura referente ao manejo da HII.

Objetivo:

O entendimento da fisiopatologia e o papel central da obesidade como fator de risco para HII abriu novas perspectivas de tratamento.

Métodos:

nessa revisão narrativa, objetivamos revisar as principais opções de tratamento disponíveis atualmente para o manejo da HII, controle da obesidade e da cefaleia.

Resultados:

Apresentação clínica: a cefaleia é o sintoma mais comum e uma importante causa de impacto na qualidade de vida, e o déficit visual é um achado comum no diagnóstico. Fisiopatologia: atualmente não existe uma teoria unificada capaz de explicar satisfatoriamente os sintomas e a evolução da doença. Um crescente corpo de evidências aponta para o papel central das alterações metabólicas e da obesidade na fisiopatologia da HII. Tratamento: a maioria dos dados publicados sobre HII estão relacionados a medidas para controle da hipertensão intracraniana e proteção da visão. Acetazolamida e Derivação Ventriculo Peritoneal são as principais alternativas com esse fim. A fenestração do nervo óptico pode ser útil como medida termporaria de controle da pressão sobre o nervo óptico e proteção contra a progressão do déficit visual. Cirurgia bariátrica se mostrou efetiva no controle da pressão intracraniana.

Conclusão:

A HII é uma causa importante de incapacidade cujo reconhecimento precoce é importante. O tratamento deve ser individualizado. Atualmente há uma importante defasagem de evidências sobre o manejo da cefaleia nesse grupo de pacientes.

Palavras-chave:
Pseudotumor Cerebral; Acetazolamida; Nervo Óptico; Líquido Cefalorraquidiano; Cirurgia Bariátrica.

INTRODUCTION

Idiopathic intracranial hypertension (IIH) is a secondary headache caused by an elevation of the intracranial pressure (ICP). IIH typically affects obese women of childbearing age11. Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013 Sep 24;81(13):1159-65. https://doi.org/10.1212/WNL.0b013e3182a55f17
https://doi.org/10.1212/WNL.0b013e3182a5...
. In a recent study in the UK, the estimated annual incidence was 4.7, which represents a growth of 108% in 14 years, and parallels the growth of obesity prevalence22. Mollan SP, Aguiar M, Evison F, Frew E, Sinclair AJ. The expanding burden of idiopathic intracranial hypertension. Eye (Lond). 2019 Mar 1;33(3):478-85. https://doi.org/10.1038/s41433-018-0238-5
https://doi.org/10.1038/s41433-018-0238-...
. Healthcare resource utilization has also grown as reflected by a rise of 442% in hospital admissions in 12 years22. Mollan SP, Aguiar M, Evison F, Frew E, Sinclair AJ. The expanding burden of idiopathic intracranial hypertension. Eye (Lond). 2019 Mar 1;33(3):478-85. https://doi.org/10.1038/s41433-018-0238-5
https://doi.org/10.1038/s41433-018-0238-...
.

CLINICAL PRESENTATION AND DIAGNOSIS

Headache is the most common symptom, frequently accompanied by transient visual obscurations, pulsatile tinnitus, back pain, dizziness, neck pain, visual loss, cognitive disturbances, radicular pain, and horizontal diplopia33. Wakerley BR, Mollan SP, Sinclair AJ. Idiopathic intracranial hypertension: update on diagnosis and management. Clin Med (Lond). 2020 Jul;20(4):384-8. https://doi.org/10.7861/clinmed.2020-0232
https://doi.org/10.7861/clinmed.2020-023...
. Papilledema is found in the vast majority of patients with confirmed IIH44. Digre KB, Nakamoto BK, Warner JEA, Langeberg WJ, Baggaley SK, Katz BJ. A comparison of idiopathic intracranial hypertension with and without papilledema. Headache. 2009 Feb 3;49(2):185-93. https://doi.org/10.1111/j.1526-4610.2008.01324.x
https://doi.org/10.1111/j.1526-4610.2008...
, and the grade of papilledema is directly related to the risk of permanent visual loss and treatment failure55. Wall M, Falardeau J, Fletcher WA, Granadier RJ, Lam BL, Longmuir RA, et al. Risk factors for poor visual outcome in patients with idiopathic intracranial hypertension. Neurology. 2015 Sep 1;85(9):799-805. https://doi.org/10.1212/WNL.0000000000001896
https://doi.org/10.1212/WNL.000000000000...
. At diagnosis, visual impairment is present in over 80% of patients, and some degree of permanent visual loss is observed in 10% of patients66. Rowe FJ, Sarkies NJ. Assessment of visual function in idiopathic intracranial hypertension: a prospective study. Eye (Lond). 1998 Jan 1;12(12):111-8. https://doi.org/10.1038/eye.1998.18
https://doi.org/10.1038/eye.1998.18...
. Another less common IIH symptom is diplopia, which is due to sixth nerve palsy, usually related to a more severe presentation.

The current diagnostic criteria for IIH requires the presence of papilledema, neuroimaging without evidence of a secondary cause of intracranial hypertension, normal CSF composition, and elevated lumbar pressure11. Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013 Sep 24;81(13):1159-65. https://doi.org/10.1212/WNL.0b013e3182a55f17
https://doi.org/10.1212/WNL.0b013e3182a5...
. The detailed diagnosis criteria is found in Table 1. IIH rarely presents without papilledema. In these cases, the alternative criteria require the presence of 3 of the 4 typical indirect findings of intracranial hypertension: empty sella, flattering of the posterior aspect of the globe, distention of the perioptic subarachnoid space with or without a tortuous optic nerve, and transverse venous sinus stenosis in the neuroimaging.

Box 1.
Modified diagnostic criteria for idiopathic intracranial hypertension.

PATHOPHYSIOLOGY

The pathogenesis of IIH is not yet clear. Dysfunction in the balance between CSF secretion and drainage seems to be the underlying cause. The high prevalence of obesity among IIH patients points to the role of metabolic changes, but this association is complex as obesity is a common condition and IIH is a rare disease. Furthermore, weight loss leads to clinical improvement77. Johnson LN, Krohel GB, Madsen RW, March GA Jr. The role of weight loss and acetazolamide in the treatment of idiopathic intracranial hypertension (pseudotumor cerebri). Ophthalmology. 1998 Dec 1;105(12):2313-7. https://doi.org/10.1016/S0161-6420(98)91234-9
https://doi.org/10.1016/S0161-6420(98)91...
, and weight gain is linked to IIH recurrence88. Ko MW, Chang SC, Ridha MA, Ney JJ, Ali TF, Friedman DI, et al. Weight gain and recurrence in idiopathic intracranial hypertension: a case-control study. Neurology. 2011 May 3;76(18):1564-7. https://doi.org/10.1212/WNL.0b013e3182190f51
https://doi.org/10.1212/WNL.0b013e318219...
. Recent evidence supports the role of adipokine, leptin, Glucagon-like peptide-1, and 11ß-hydroxysteroid dehydrogenase (11-ßHSD1) in the pathophysiology of IIH, highlighting the metabolic nature of this condition99. Hornby C, Mollan SP, Botfield H, O’Reilly MW, Sinclair AJ. Metabolic concepts in idiopathic intracranial hypertension and their potential for therapeutic intervention. J Neuroophthalmol. 2018 Dec;38(4):522-30. https://doi.org/10.1097/WNO.0000000000000684
https://doi.org/10.1097/WNO.000000000000...
. Understanding of the metabolic pathways involved in ICP regulation has led to the development of novel targeted therapies such as bariatric surgery1010. Mollan SP, Mitchell JL, Ottridge RS, Aguiar M, Yiangou A, Alimajstorovic Z, et al. Effectiveness of bariatric surgery vs community weight management intervention for the treatment of idiopathic intracranial hypertension: a randomized clinical trial. JAMA Neurol. 2021 Jun 1;78(6):678-86. https://doi.org/10.1001/jamaneurol.2021.0659
https://doi.org/10.1001/jamaneurol.2021....
, 11-ßHSD1 inhibitor1111. Markey KA, Ottridge R, Mitchell JL, Rick C, Woolley R, Ives N, et al. Assessing the efficacy and safety of an 11β-Hydroxysteroid dehydrogenase type 1 inhibitor (AZD4017) in the idiopathic intracranial hypertension drug trial, IIH:DT: clinical methods and design for a phase II randomized controlled trial. JMIR Res Protoc. 2017 Sep 18;6(9):e181. https://doi.org/10.2196/resprot.7806
https://doi.org/10.2196/resprot.7806...
and GLP-1 receptor agonist.

In IIH patients, the elevated cranial pressure induces microstructural compression of the optic nerve, impairing axoplasmic flow and causing papilledema and visual loss1212. Hoffmann J, Kreutz KM, Csapó-Schmidt C, Becker N, Kunte H, Fekonja LS, et al. The effect of CSF drain on the optic nerve in idiopathic intracranial hypertension. J Headache Pain. 2019 May 23;20(1):59. https://doi.org/10.1186/s10194-019-1004-1
https://doi.org/10.1186/s10194-019-1004-...
. The main goal of therapies directly targeting ICP control is to reduce transient and permanent visual loss.

Headache is the most common symptom and the cause of significant quality of life impairment for IIH patients1313. Mulla Y, Markey KA, Woolley RL, Patel S, Mollan SP, Sinclair AJ. Headache determines quality of life in idiopathic intracranial hypertension. J Headache Pain. 2015 May 15;16(45):521. https://doi.org/10.1186/s10194-015-0521-9
https://doi.org/10.1186/s10194-015-0521-...
. The most common phenotype is a migraine-like headache1414. Mollan SP, Hoffmann J, Sinclair AJ. Advances in the understanding of headache in idiopathic intracranial hypertension. Curr Opin Neurol. 2019 Feb;32(1):92-8. https://doi.org/10.1097/WCO.0000000000000651
https://doi.org/10.1097/WCO.000000000000...
. Although headache seems to be related to the raised ICP, a substantial number of patients present with a persistent headache after ICP normalization1515. Yri HM, Rönnbäck C, Wegener M, Hamann S, Jensen RH. The course of headache in idiopathic intracranial hypertension: a 12-month prospective follow-up study. Eur J Neurol. 2014 Dec;21(12):1458-64. https://doi.org/10.1111/ene.12512
https://doi.org/10.1111/ene.12512 ...
. Despite the high frequency and burden of headache for IIH patients, to date little is known about the pathophysiology, and no directed trials have investigated headache treatment.

TREATMENT

IIH treatment has three main objectives: body weight loss, vision protection, and headache control.

To date, weight loss is the only modifying disease measure. All patients with BMI ≥ 30 kg/ m² should be oriented for weight control. A multidisciplinary team (nutritionist, endocrinologist) is sometimes necessary to help patients in weight management. The precise amount of weight reduction that should be aimed for IIH remission is not established. However, 5-15% weight gain is a risk factor for developing IIH, so it is reasonable to advise patients to lose at least 15% weight1616. Daniels AB, Liu GT, Volpe NJ, Galetta SL, Moster ML, Newman NJ, et al. Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol. 2007 Apr 1;143(4):P635-41. https://doi.org/10.1016/j.ajo.2006.12.040
https://doi.org/10.1016/j.ajo.2006.12.04...
.

PHARMACOLOGICAL TREATMENT

The main goal of the pharmacological treatment of IIH is to protect from visual loss. Acetazolamide is the first-choice drug, and its use in patients with mild visual loss can result in improvement in visual field function and quality of life1717. Wall M, McDermott MP, Kieburtz KD, Corbett JJ, Feldon SE, Friedman DI, et al. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial. JAMA. 2014 Apr 23-30;311(16):1641-51. https://doi.org/10.1001/jama.2014.3312
https://doi.org/10.1001/jama.2014.3312...
. The starting dose is 250-500mg twice a day, and it can be titrated until a maximal dose of 4g daily. Common adverse effects are diarrhea, dysgeusia, fatigue, nausea, paresthesia, tinnitus, vomiting, depression, and rarely renal stones. Periodic monitoring of serum electrolytes and venous gasometry should be performed1818. Mollan SP, Davies B, Silver NC, Shaw S, Mallucci CL, Wakerley BR, et al. Idiopathic intracranial hypertension: consensus guidelines on management. J Neurol Neurosurg Psychiatry. 2018 Sep 13;89(10):1088-100. https://doi.org/10.1136/jnnp-2017-317440
https://doi.org/10.1136/jnnp-2017-317440...
.

An open-label study suggested similar efficacy of acetazolamide and topiramate (50-200mg daily)1919. Celebisoy N, Gökçay F, Şirin H, Akyürekli Ö. Treatment of idiopathic intracranial hypertension: topiramate vs acetazolamide, an open-label study. Acta Neurol Scand. 2007 Nov;116(5):322-7. https://doi.org/10.1111/j.1600-0404.2007.00905.x
https://doi.org/10.1111/j.1600-0404.2007...
. Topiramate might be very helpful considering the frequency of obesity and migraine among IIH patients. Furosemide (maximal dose of 40mg twice a day) is a third option if the previous drugs cannot be tolerated2020. Wakerley BR, Tan MH, Ting EY. Idiopathic intracranial hypertension. Cephalalgia. 2015 Mar 1;35(3):248-61. https://doi.org/10.1177/0333102414534329
https://doi.org/10.1177/0333102414534329...
.

SURGICAL PROCEDURES

In the presence of imminent visual deterioration, surgical management is an effective alternative for visual protection. CSF diversion and optic nerve sheath fenestration (ONSF) have been employed in the short term.

CSF DIVERSION SURGERY

In many centers, the neurosurgical CSF diversion is a surgical first-line choice. Ventriculoperitoneal shunt (VPS) and lumboperitoneal shunt (LPS) are both effective in patients with progressive vision loss based on case series1818. Mollan SP, Davies B, Silver NC, Shaw S, Mallucci CL, Wakerley BR, et al. Idiopathic intracranial hypertension: consensus guidelines on management. J Neurol Neurosurg Psychiatry. 2018 Sep 13;89(10):1088-100. https://doi.org/10.1136/jnnp-2017-317440
https://doi.org/10.1136/jnnp-2017-317440...
. The shunt procedure did not reverse established visual loss but was effective in stabilizing the worsening. In 53 patients’ retrospective case series, patients who underwent a CSF shunt presented papilledema reduction and improvement in visual acuity and tinnitus. Fundus examination showed a significant reduction in the number of patients with papilledema from 92% at baseline to 65% at 6 months, 48% at 12 months, and 44% at 24 months after shunt surgery. The LPS was the most performed procedure in the studies, but with a high rate of shunt revision when compared to VPS, hence the last one is most recommended. Ideally, the surgical approach should be performed by an experienced neurosurgeon with an interest in CSF disorders2121. Sinclair AJ, Kuruvath S, Sen D, Nightingale PG, Burdon MA, Flint G. Is cerebrospinal fluid shunting in idiopathic intracranial hypertension worthwhile? A 10-year review. Cephalalgia. 2011 Dec 1;31(16):1627-33. https://doi.org/10.1177/0333102411423305
https://doi.org/10.1177/0333102411423305...
.

In the case series, headache recurrence was documented in about 60-70% of patients by 1-year post-procedure. Therefore, shunts should not be indicated for the treatment of IIH-associated headaches in the absence of visual loss2222. Mollan SP, Grech M, Sinclair AJ. Headache attributed to idiopathic intracranial hypertension and persistent post-idiopathic intracranial hypertension headache: a narrative review. Headache. 2021 Jun 9;61(6):808-16. https://doi.org/10.1111/head.14125
https://doi.org/10.1111/head.14125...
. More than half of patients undergoing shunts will require surgical revision and about one-third underwent multiple revisions. Other complications are reported, such as abdominal pain, valve and/or circuit obstruction, infection, headaches due to low CSF pressure, subdural hematoma, and tonsillar herniation. Adjustable valves should be preferred because of the risk of low-pressure headaches. Deaths are reported in shunt placement; however, no data were obtained from IIH studies2323. Abubaker K, Ali Z, Raza K, Bolger C, Rawluk D, O’Brien D. Idiopathic intracranial hypertension: lumboperitoneal shunts versus ventriculoperitoneal shunts -- case series and literature review. Br J Neurosurg. 2011 Feb 16;25(1):94-9. https://doi.org/10.3109/02688697.2010.544781
https://doi.org/10.3109/02688697.2010.54...
. Despite the adverse events, CSF derivations are still the most available procedure in fulminant IIH or medication failure, with positive visual outcomes.

OPTIC NERVE SHEATH FENESTRATION

The optic nerve sheath fenestration (ONSF) is a technique with a lower complication rate and no reported mortality. Therefore, ONSF is preferred by many experts when considering the re-approaches after the shunt placement2424. Spitze A, Malik A, Al-Zubidi N, Golnik K, Lee AG. Optic nerve sheath fenestration vs cerebrospinal diversion procedures: what is the preferred surgical procedure for the treatment of idiopathic intracranial hypertension failing maximum medical therapy? J Neuroophthalmol. 2013 Jun;33(2):183-8. https://doi.org/10.1097/WNO.0b013e318292d06f
https://doi.org/10.1097/WNO.0b013e318292...
. The ONSF may be performed by neuro-ophthalmologists experienced with the technique, which limits access in many centers. Reports and case series have shown positive outcomes with this approach in improving visual acuity and visual field in patients with medication failure. In the majority of reported cases, ONSF was bilateral, but unilateral ONSF can be an option especially when there is asymmetric visual impairment, and may improve not only the operated eye, but also the non-operated eye. In the unilateral technique, the eye chosen for the fenestration is the one with the worst visual performance. The possibility to perform a unilateral ONSF with bilateral results reduces the time of anesthesia and possibility of complications2525. Banta JT, Farris BK. Pseudotumor cerebri and optic nerve sheath decompression. Ophthalmology. 2000 Oct 1;107(10):P1907-12. https://doi.org/10.1016/s0161-6420(00)00340-7
https://doi.org/10.1016/s0161-6420(00)00...
.

The rate of OSNF’s complications is low and the main adverse effects are transient, not needing further surgery procedures: double vision, anisocoria, and ocular hemorrhages. Permanent complications such as central retinal artery occlusion are reported in < 1% of the cases2626. Gilbert AL, Chwalisz B, Mallery R. Complications of optic nerve sheath fenestration as a treatment for idiopathic intracranial hypertension. Semin Ophthalmol. 2018 Feb 8;33(1):36-41. https://doi.org/10.1080/08820538.2017.1353810
https://doi.org/10.1080/08820538.2017.13...
. OSNF is also considered by some experts as a first-line approach to fulminant visual loss to protect vision while effective weight loss treatment is achieved. In case of failure, the patient should undergo a more invasive procedure such as CSF shunt, avoiding the need for multiple procedures. The results of fenestration in improving headaches are conflicting, with a single review with about 50% improvement and other studies with 20-30%. The pathophysiology of headache improvement is uncertain and may result from a placebo effect2424. Spitze A, Malik A, Al-Zubidi N, Golnik K, Lee AG. Optic nerve sheath fenestration vs cerebrospinal diversion procedures: what is the preferred surgical procedure for the treatment of idiopathic intracranial hypertension failing maximum medical therapy? J Neuroophthalmol. 2013 Jun;33(2):183-8. https://doi.org/10.1097/WNO.0b013e318292d06f
https://doi.org/10.1097/WNO.0b013e318292...
. The OSNF is a safe, less invasive, and effective alternative for progressive visual loss in patients with medication failure in asymmetric papilledema causing unilateral visual loss1818. Mollan SP, Davies B, Silver NC, Shaw S, Mallucci CL, Wakerley BR, et al. Idiopathic intracranial hypertension: consensus guidelines on management. J Neurol Neurosurg Psychiatry. 2018 Sep 13;89(10):1088-100. https://doi.org/10.1136/jnnp-2017-317440
https://doi.org/10.1136/jnnp-2017-317440...
.

VENOUS SINUS STENTING

A more recent therapeutic approach for IIH is venous sinus stenting, reported for the first time in 20022727. Higgins JNP, Owler BK, Cousins C, Pickard JD. Venous sinus stenting for refractory benign intracranial hypertension. Lancet. 2002 Jan 19;359(9302):228-30. https://doi.org/10.1016/S0140-6736(02)07440-8
https://doi.org/10.1016/S0140-6736(02)07...
. Since then, an increasing number of case series have shown promising results. In a large meta-analysis with 474 patients, the overall rate of improvement in papilledema, headache and pulsatile tinnitus was 93.7% (95% CI 90.5% to 96.9%), 79.6% (95% CI 73.3% to 85.9%) and 90.3% (95% CI 83.8% to 96.70%), respectively (28). It may be reasonable for highly selected IIH patients with venous sinus stenosis and elevated pressure gradient across the stenosis region (8mm Hg or higher) in whom standard therapies failed1818. Mollan SP, Davies B, Silver NC, Shaw S, Mallucci CL, Wakerley BR, et al. Idiopathic intracranial hypertension: consensus guidelines on management. J Neurol Neurosurg Psychiatry. 2018 Sep 13;89(10):1088-100. https://doi.org/10.1136/jnnp-2017-317440
https://doi.org/10.1136/jnnp-2017-317440...
. Regarding the procedure, venography and manometry should ideally be performed with the patient awake, along with dual or single antiplatelet drugs administered before as well as at least 3-6 months following stenting2929. Fargen KM, Liu K, Garner RM, Greeneway GP, Wolfe SQ, Crowley RW. Recommendations for the selection and treatment of patients with idiopathic intracranial hypertension for venous sinus stenting. J Neurointerv Surg. 2018 Nov 20;10(12):1203-8. https://doi.org/10.1136/neurintsurg-2018-014042
https://doi.org/10.1136/neurintsurg-2018...
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Recurrence of IIH symptoms after stenting occurred in 9.8% (95% CI 6.7% to 13%) of patients2828. Nicholson P, Brinjikji W, Radovanovic I, Hilditch CA, Tsang ACO, Krings T, et al. Venous sinus stenting for idiopathic intracranial hypertension: a systematic review and meta-analysis. J Neurointerv Surg. 2019 Apr;11(4):380-5. https://doi.org/10.1136/neurintsurg-2018-014172
https://doi.org/10.1136/neurintsurg-2018...
. High BMI, African-American race, female gender, pure extrinsic compression of the transverse-sigmoid junction, highly raised opening pressures and persisting papilledema post-procedure possibly increase the risk of stent failure3030. Gurney SP, Ramalingam S, Thomas A, Sinclair AJ, Mollan SP. Exploring the current management idiopathic intracranial hypertension, and understanding the role of dural venous sinus stenting. Eye Brain. 2020 Jan 14;12:1-13. https://doi.org/10.2147/EB.S193027
https://doi.org/10.2147/EB.S193027 ...
. On the other hand, patients who had higher mean pressure gradients and higher changes in pressure gradients after stent placement seem to have favorable outcomes3131. McDougall CM, Ban VS, Beecher J, Pride L, Welch BG. Fifty shades of gradients: Does the pressure gradient in venous sinus stenting for idiopathic intracranial hypertension matter? A systematic review. J Neurosurg. 2018 Mar 2;130(3):999-1005. https://doi.org/10.3171/2017.8.JNS17459
https://doi.org/10.3171/2017.8.JNS17459...
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The rate of major complications (subdural hematoma, subarachnoid hemorrhage, thrombosis, fistulae) was 1.9% (95% CI 0.07% to 3.1%) and the overall mortality was 0%2828. Nicholson P, Brinjikji W, Radovanovic I, Hilditch CA, Tsang ACO, Krings T, et al. Venous sinus stenting for idiopathic intracranial hypertension: a systematic review and meta-analysis. J Neurointerv Surg. 2019 Apr;11(4):380-5. https://doi.org/10.1136/neurintsurg-2018-014172
https://doi.org/10.1136/neurintsurg-2018...
. Short-lived ipsilateral, stent-adjacent headache was the most common complication (30%)3232. Dinkin MJ, Patsalides A. Venous sinus stenting for idiopathic intracranial hypertension: Where are we now? Neurol Clin. 2017 Feb;35(1):59-81. https://doi.org/10.1016/j.ncl.2016.08.006
https://doi.org/10.1016/j.ncl.2016.08.00...
. The outcomes and the eligibility for the procedure were not standardized among studies, and randomized clinical trials are lacking.

BARIATRIC SURGERY

As obesity is the main modifiable risk factor for IIH88. Ko MW, Chang SC, Ridha MA, Ney JJ, Ali TF, Friedman DI, et al. Weight gain and recurrence in idiopathic intracranial hypertension: a case-control study. Neurology. 2011 May 3;76(18):1564-7. https://doi.org/10.1212/WNL.0b013e3182190f51
https://doi.org/10.1212/WNL.0b013e318219...
researchers have hypothesized that treatment targeting body weight control improves clinical outcome (10,14). One randomized controlled trial compared bariatric surgery (BS) (N= 33) to community weight management (CWM) (N= 33). The primary outcome evaluated was change in ICP after 12 months. Secondary outcomes included change in ICP after 24 months, visual acuity, Headache Impact Test score (HIT-6), perimetric mean deviation, and quality of life (measured by the 36-item Short Form Health Survey). At baseline, the mean BMI was 43.7 in the CWM group and 44.2 in the BS group. In the surgery arm, different procedures were accepted, and the main method was Roux-en-Y gastric bypass (44%), followed by gastric banding (37%) and laparoscopic sleeve gastrectomy (18.5%). At 12 months the mean ICP decreased from 34.8 to 26.4 cm CSF (-8.7 cm CSF; P <0.001) in the BS arm and from 34.6 cm CSF to 32.0 cm CSF (P =0.08). After 24 months the change in ICP demonstrated increasing effect size with a difference between the 2 arms of -8.2 cm CSF (P<0.001). Weight control was more effective in the BS arm compared to the CWM, with a difference of mean weight loss and excess weight loss of -18.3% (P< 0.001), and -46.4% (P<0.001), respectively. No difference was found between arms regarding perimetric mean deviation, HIT-6, or quality of life. The authors suggest that the negative secondary outcomes might have been influenced by the low number of patients recruited, which was expected considering the complex nature of the surgical intervention. Although more data is warranted to confirm the clinical benefits of BS for IIH treatment, this trial supports it as an effective treatment for patients with IIH and a BMI of 35 or higher.

HEADACHE MANAGEMENT

Headache is the most common symptom and near-universal sequela of IIH. Despite the high morbidity, there is a lack of evidence to guide persistent headache management1414. Mollan SP, Hoffmann J, Sinclair AJ. Advances in the understanding of headache in idiopathic intracranial hypertension. Curr Opin Neurol. 2019 Feb;32(1):92-8. https://doi.org/10.1097/WCO.0000000000000651
https://doi.org/10.1097/WCO.000000000000...
. The treatments used for visual protection, either clinical with acetazolamide or surgical, have not shown benefit in improving headaches and therefore should not be prescribed for this purpose1818. Mollan SP, Davies B, Silver NC, Shaw S, Mallucci CL, Wakerley BR, et al. Idiopathic intracranial hypertension: consensus guidelines on management. J Neurol Neurosurg Psychiatry. 2018 Sep 13;89(10):1088-100. https://doi.org/10.1136/jnnp-2017-317440
https://doi.org/10.1136/jnnp-2017-317440...
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Management is mostly based on off-label treatments according to headache phenotype. IIH-related headaches can change phenotype throughout the disease, and a comprehensive clinical characterization is extremely important for phenotypic definition. A mixture of diverse phenotypes such as migraine, analgesic overuse headache, tension-type headache, and even CSF hypotension headache secondary to drainage procedures is not uncommon3333. Mollan SP, Grech O, Sinclair AJ. Headache attributed to idiopathic intracranial hypertension and persistent post-idiopathic intracranial hypertension headache: a narrative review. Headache. 2021 Jun 9;61(6):808-16. https://doi.org/10.1111/head.14125
https://doi.org/10.1111/head.14125...
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In almost 68% of IIH patients, the predominant phenotype is migraine, and therefore, prophylactic migraine therapy is commonly the treatment of choice. Attention should be given to avoid prophylactics that increase weight and worsen psychiatric comorbidities such as depression. Topiramate is the preferred oral prophylactic among neurologists. It reduces appetite, causes weight loss, and there is evidence that it promotes some degree of reduction in ICP. A limiting factor for topiramate is tolerability of the most reported adverse effects, like paresthesia and cognitive complaints. There are no randomized trials comparing the antimigraine therapeutics in IIH3333. Mollan SP, Grech O, Sinclair AJ. Headache attributed to idiopathic intracranial hypertension and persistent post-idiopathic intracranial hypertension headache: a narrative review. Headache. 2021 Jun 9;61(6):808-16. https://doi.org/10.1111/head.14125
https://doi.org/10.1111/head.14125...
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Recently, a prospective open-label study evaluated patients with persistent headaches using Erenumab, a calcitonin gene-related peptide (CGRP) receptor monoclonal antibody. Erenumab significantly reduced (by 71%) days with moderate to severe headache and days with any headache (by 45%) from baseline to 12 months. In addition to improvement in pain, there was also a significant improvement in presenteeism, absenteeism, and analgesic use days. Erenumab had high tolerability without any patient leaving the study due to side effects. CGRP has been studied and implicated in the pathophysiology of migraine and may play a role in the pathophysiology of IIH-related headaches. Therefore, Anti-CGRP antibodies may be a potential therapeutic approach for IIH persistent headache3434. Mollan SP, Grech O, Sinclair AJ. Headache attributed to idiopathic intracranial hypertension and persistent post-idiopathic intracranial hypertension headache: a narrative review. Headache. 2021 Jun 9;61(6):808-16. https://doi.org/10.1111/head.14125
https://doi.org/10.1111/head.14125...
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Publication Dates

  • Publication in this collection
    12 Aug 2022
  • Date of issue
    May 2022

History

  • Received
    15 Mar 2022
  • Accepted
    29 Apr 2022
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