Case report Case series of six patients diagnosed and managed for idiopathic intracranial hypertension at a tertiary institution eye centre Naa N. Tagoe1, Vera M. Beyuo2 and Kwesi N. Amissah-Arthur2 Ghana Med J 2019; 53(1): 79-87 http://dx.doi.org/10.4314/gmj.v53i1.12 1Lions Eye Centre, Korle Bu Teaching Hospital Accra, Ghana 2Department of Surgery, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Legon, Accra, Ghana. Corresponding author: Naa Naamuah Tagoe E-mail: naanaamuahtagoe@gmail.com Conflict of interest: None declared SUMMARY Background: Idiopathic Intracranial Hypertension (IIH) occurs secondary to raised intracranial pressure (ICP) of unknown etiology and is diagnosed when all other causes of raised ICP have been excluded. It can leave devastating sequelae such as permanent visual loss, hence the need for timely diagnosis and treatment. Anecdotally, one or two cases of idiopathic intracranial hypertension (IIH) previously presented at the Eye Centre, KBTH yearly. However, six cases were seen within a 6-month period, prompting the need to study the clinical features of IIH in this population. Objective: We aim to evaluate the clinical features of patients presenting with IIH at KBTH. Methodology: This is a retrospective case series with contemporaneous collection of data of six patients who presented to the Eye Centre (KBTH) between October 2016 and March 2017 with clinical features suggestive of IIH. The patients were evaluated and diagnosed based on clinical judgement as well as using the modified Dandy criteria. Results: All six patients were female and all except one were obese. The age range was 8 to 40 years with median 22.5 years. Symptoms in the 8-year-old were preceded by oral doxycycline for acne treatment. One patient had a history of using oral contraceptive pills prescribed for irregular menses. Clinical features of blurred vision, headache, and papilloedema were relieved with oral acetazolamide. Conclusion: The upsurge of IIH may be due to the increased incidence of obesity in Ghana. Timely diagnosis and treatment is needed to avoid irreversible blindness. Funding: None Keywords: headaches, idiopathic intracranial hypertension, obesity, blindness, raised intracranial pressure. INTRODUCTION Idiopathic intracranial hypertension (IIH) occurs when The currently used term “idiopathic intracranial there is raised intracranial pressure (ICP) of unknown hypertension” reflects the general lack of understanding etiology and is diagnosed when all other causes of raised of the pathophysiology of this disorder. ICP have been excluded.1 It was previously known as “Pseudo tumor cerebri” and “benign intracranial Diagnosis is made using the modified Dandy criteria: hypertension”. It is a diagnosis of exclusion. Though 1) Symptoms and signs of raised ICP i.e. headache, previously referred to as benign, it can leave devastating nausea, vomiting, pulsatile tinnitus, transient visual sequelae such as permanent visual loss in 31% of cases,2 obscurations, papilledema) hence the need for early diagnosis and intervention. 2) Absence of localizing signs, except for abducens nerve Suggestions have been made that the terms “primary” palsy and “secondary” intracranial hypertension should be 3) No identifiable cause for raised ICP on neuroimaging considered to describe these two groups of patients: 1) (brain MRI or CT scan) the young obese women with isolated raised ICP and no 4) Cerebrospinal fluid (CSF) opening pressure of greater obvious precipitating factors and 2) patients with isolated than 25 cmH2O, with normal CSF composition raised ICP associated with factors such as endocrine 5) No alternate explanation for the raised ICP disorders, anemia, obstructive sleep apnea, medications, or cerebral venous sinus stenosis.3,4 79 www.ghanamedj.org Volume 53 Number 1 March 2019 Case report Anecdotally, only one or 2 cases of idiopathic visual acuity was 6/9 in both eyes. The anterior segment intracranial hypertension (IIH) presented at the Eye examination was essentially normal except for the right Centre, KBTH in a year. However, six cases were seen pupil which reacted sluggishly and left pupil which had a within a 6-month period, thus prompting the need to Relative Afferent Pupillary Defect (RAPD). Her colour study the clinical features of IIH in this population. The vision was moderately impaired (11/20 on the right and prevalence of IIH in sub Saharan Africa is not 12/20 on the left using the Ishihara chart).The intraocular documented, however there have been case reports from pressures were 17mmHg and 16mmHg in her right and Nigeria and South Africa.1, 2 left eyes respectively and examination of the optic discs revealed marked papilloedema (Frisen stage 4). There is still a lot that is not known about the exact pathophysiology of IIH. It is usually a diagnosis of Cranial computerized tomography (CT) scan was exclusion. It may be a diagnostic challenge in low reported as normal. Our clinical diagnosis was resource settings such as in Sub Saharan Africa. More Papilloedema secondary to possible Idiopathic awareness needs to be created about this disease in Africa Intracranial hypertension. She was commenced on oral and protocols for diagnosis and management that are acetazolamide 500mg 4 times daily and referred to a suitable for our setting established, to achieve good dietician for weight reduction. 4 weeks post treatment her outcomes and prevent permanent visual loss. visual acuity had not improved. The patient revealed that she had stopped taking acetazolamide after 2 weeks The goal of this study was to document the epidemiology because it made her feel unwell. of patients presenting with IIH at KBTH. The specific objectives were: 1. To document the presenting symptoms of patients with IIH at KBTH 2. To study the signs of patients presenting with IIH at KBTH and 3. To document the demographic features of patients with IIH METHODS This was a retrospective case series with contemporaneous collection of data of six patients who presented to the Eye Centre (KBTH) between October 2016 and March 2017 with symptoms and signs suggestive of idiopathic intracranial hypertension. This retrospective case series conformed to the Declaration of Helsinki. Patients were evaluated, investigated and Case 1a Elevation of the entire nerve head, obscuration diagnosed based on clinical judgement as well as using of all borders and peripapillary halo (RE) the modified Dandy criteria. CASE REPORTS CASE 1 A 31-year-old female presented on September 13, 2016 with a 2- week history of severe headaches and blurred vision. She had been diagnosed of hypertension during her last pregnancy 4 years prior and her blood pressure remained persistently high despite treatment. Her last BP checked was 148/85mmHg. Two weeks prior to presentation she started experiencing severe global headaches associated with tinnitus and blurred vision and her symptoms were worse in the morning. There was no history of nausea or vomiting. Case 1b Elevation of the entire nerve head, obscuration of all borders and peripapillary halo (LE) On examination she weighed 90 kilograms (kg), height was 1.62m and her Body Mass Index (BMI) was 34.3. Her blood pressure was 140/90mmHg. Her best corrected 80 www.ghanamedj.org Volume 53 Number 1 March 2019 Case report She was counseled on compliance and the dose of Child was referred to dieticians for weight reduction and acetazolamide was reviewed to 250mg twice daily. By started on oral acetazolamide, an initial dose of 375mg the 12th week the headaches and tinnitus had resolved. tid, and stepped up after one week to 500mg tid. On her Her blood pressure (BP) was 110/80mmHg and her 3rd clinic visit, the headaches had subsided, diplopia had weight had reduced to 87kg, with a BMI of 33.2. In resolved and visual acuity was 6/9 in right eye (RE) and addition, her best corrected visual acuity had improved to 6/6 in left eye (LE). 6/6 in both eyes, her colour vision had returned to normal and the papilloedema had resolved. She complained of paraesthesia, hence the morning dose of acetazolamide was tapered to 250mg. At her last CASE 2 consultation, 3 months since her initial presentation her An 8- year- old girl presented on 14th September, 2016, best visual acuity was 6/6 in both eyes, the squint had with a 4-month history of recurrent headaches and 3- resolved and her optic nerves were normal. She is week history of diplopia. She had been on oral currently on oral acetazolamide 125mg daily and still doxycycline (a derivative of tetracycline) for acne being followed up. treatment 2-3 weeks prior to the onset of her symptoms. When the headaches started she reported to a couple of CASE 3 health facilities and had been placed on different A 20-year-old female university student presented on analgesics. It was when eye deviation was noticed three October 18, 2016 with a month’s history of poor vision weeks prior to presentation that the mother was advised in both eyes, worse in the right. She started experiencing by a doctor relation to do a cranial MRI after which they black outs initially and later developed severe headaches reported to our centre. On examination, the child was that were frontal, radiating to the eyes. She reported to a found to be obese. Her weight was 46kg, height 1.3m, tertiary facility where a Cranial CT scan was done and with a BMI of 27.2. reported as normal. She was subsequently put on some eye care supplements. However when there was no significant improvement in her symptoms she reported to a private eye clinic where she was commenced on oral acetazolamide 250mg bd and referred to the Eye Centre, Korle Bu Teaching Hospital for further management. On examination she weighed 124kg and her blood Case 2a severely swollen disc, dome-shaped protrusions, pressure was 149/96mmHg. Her best corrected visual peripapillary haemorrhages with macula exudates (RE). acuity was 6/36 in RE and 6/12 in LE. There was normal Before and 3 months after photos ocular alignment with no ophthalmoplegia. Fundus examination showed stage 5 papilloedema (Frisen grading), haemorrhages, exudates, macula oedema with macula star. A lumbar puncture was done and the opening pressure was 35cmH2O. Test results of CSF biochemistry and bacteriology were negative. Case 2b Severely swollen disc, dome-shaped protrusions, peripapillary haemorrhages with macula exudates (RE). Before and 3 months post treatment Her blood pressure- 100/60mmHg. The best corrected visual acuity was 6/36 in both eyes (moderately impaired) and she had a right exotropia (divergent squint) Case 3a Severely swollen disc, obscuration of all vessels, of 20 prism diopters. Fundus examination revealed stage complete obliteration of cup, retinal haemorrhages and 5 (Frisen staging) disc swelling/papilloedema with a macular exudates (RE) macula star. A lumbar puncture was done but the opening pressure could not be measured due to the unavailability of a manometer. MRI done showed a swollen optic nerve. 81 www.ghanamedj.org Volume 53 Number 1 March 2019 Case report Case 3b. Severely swollen disc, obscuration of all vessels, complete obliteration of cup, retinal Case 4b Disc swelling, peripapillary cotton wool spots haemorrhages and macular exudates (LE) (LE) The patient was referred to see the dieticians for weight Fundus examination revealed bilateral disc oedema reduction. The dose of Acetazolamide was increased (papilloedema), haemorrhages and cotton wool spots. initially to 500mg three times daily and a week later to The macula was normal on both sides. The CSF opening 500mg 6 hourly. On week two review visit, her weight pressure was 55cmH2O. She was referred to dieticians for had dropped to 121kg, the symptoms of headache had weight reduction and continued on oral acetazolamide improved, and visual acuity had improved to 6/24 in the 500mg bd and oral furosemide 80mg bd which had been right eye. By one-month review, visual acuity in the right started by her physicians. This patient has been lost to eye had improved to 6/18 while that of the left eye follow up. remained 6/12. The patient returned to school which was in another region and has since been lost to follow up. CASE 5 She was however contacted via phone and stated that she A 24-year-old female presented with a 3- week history was doing well. of headache and blurred vision. She had associated symptoms of photophobia, diplopia which was binocular, CASE 4 constant and horizontal as well as transient visual A 21-year- old female was referred from the obscurations (TVOs). She also had tinnitus, nausea and neurosurgical unit on 20th October 2016, with a diagnosis neck pain. The patient had a history of irregular menses of IIH. She presented with headaches, nuchal rigidity and for which she was being managed by the gynaecologists horizontal diplopia. On examination, she was obviously and had been placed on oral contraceptive pills (OCP). obese. Her weight was 104kg, height of 1.76, with BMI The symptoms started around the same time she of 33.57. Her best corrected visual acuity was 6/6 in commenced the OCPs. On examination her weight was -1 both eyes and she had bilateral esotropia. 100kg and height 1.73m, with BMI 33.4. Her blood pressure was 120/72mmHg. The best corrected visual acuity was 6/6 in the right eye and 6/9 in the left eye. Colour vision was normal at 11/12 in both eyes using Ishihara colour plates. Examination of the optic discs revealed Grade 3 papilloedema. Cranial CT scan showed small ventricles but was otherwise normal. A lumbar puncture was done but the opening pressure was not measured. Results of her CSF biochemistry and bacteriology were negative. Case 4a Disc swelling, peripapillary haemorrhages, cotton wool spots (RE) 82 www.ghanamedj.org Volume 53 Number 1 March 2019 Case report Case 6a Obscuration of major vessels inferiorly, circumferential blurring of disc margins, superior peripapillary haemorrhage (RE) Case 5a. Obscuration of major vessels inferiorly, peripapillary haemorrhages (RE) Figure 5b Obscuration of major vessels superiorly, Case 6b. Obscuration of major vessel inferiorly, peripapillary halo (LE) circumferential blurring of disc margins (LE) She was initially seen by physicians who started her on Her visual acuity was counting fingers at 4 metres in both IV methylprednisolone, IV Ceftriaxone, oral eyes, best corrected to 6/6 with glasses. Colour vision acetazolamide 250mg tid and 2 doses of IV mannitol. She was normal; 15/15 (Ishihara colour vision chart) and was subsequently referred to the Eye Centre, KBTH funduscopy revealed moderate papilloedema. (Frisen where upon complaints of persistent headache, the dose grade 3). Cranial CT scan showed an empty sella. She of acetazolamide was increased to 250mg qid. A week was referred to the dieticians for weight loss and later she still had headaches hence the dose of commenced on oral acetazolamide 250mg tid. Her acetazolamide was further increased to 500mg tid and symptoms of headache, vomiting and tinnitus abated on referred to dieticians for weight loss. By week 3, the this dose. headaches, diplopia and blurred vision had subsided. However, she developed an urticarial rash hence the dose DISCUSSION of acetazolamide was reduced to 500mg bd interspersed Several studies have shown that IIH is more common in with oral furosemide 40mg bd which was well tolerated. women and obese individuals.5-8 Among women aged 20–44 years who are 20% or more above ideal body CASE 6 weight, the incidence increases to approximately A 40-year-old woman presented with a prolonged history 19/100,000, about 20 times the incidence in the general of headache and a week history of floater in her left eye. population and similar to the incidence of multiple She reported to a private eye clinic where she was sclerosis.5,9Prior to the period of this report, very few examined and subsequently referred to our facility for cases of suspected IIH were seen in the department. This management. Prior to the appearance of the floater she could be attributable to the improvement in diagnostic had been experiencing severe headaches associates with capabilities in our centre or due to the increasing vomiting and tinnitus. She frequently took amoxicillin- incidence of obesity in the developing world of which clavulanic acid for recurrent tonsillitis, otherwise there Ghana is inclusive. The prevalence of IIH in sub Saharan was no other drug history of significance. On Africa is not documented, however there have been case examination her BMI was 40.98 (weight was 97.2kg, reports from Nigeria and South Africa.10,11 height 1.54m), and her BP was138/85mmHg 83 www.ghanamedj.org Volume 53 Number 1 March 2019 Case report A study in Libya between 1982 and 1989 with 81(76 18,19or deficiency, and systemic conditions (such as female, 5 male) patients diagnosed with IIH revealed the pregnancy, menstrual irregularities, polycystic ovarian following annual incidence rates: syndrome, anaemia, and obstructive sleep apnoea).20,21 2.2cases/100,000 population (total population) have been found in some studies to be associated, 12 cases/100,000 women aged 15-44 years.12 precipitate or worsen IIH. All six patients in this study were female and all except All 6 cases in this series experienced headaches. This is one were obese. This is in line with several other studies corroborated by studies by Wall M et al and Giuseffi V23 that observed that IIH is more common in women and who reported headache as the commonest presenting obese individuals.5-8 In a recent multicenter case-control symptom. Headache, though the most common symptom study of newly-diagnosed women with IIH compared to at presentation,22,23 is less likely to be reported by men women who were newly-diagnosed with other neuro- than by women.24 The headache of IIH is typically ophthalmologic disorders, it was found that higher body pulsatile, global, worse after waking, and exacerbated by mass index is associated with a greater risk of IIH.13 The manoeuvres that increase intracranial pressure (ICP). same study also showed that even non-obese patients Features consistent with migraine, including unilateral were at greater risk for IIH if they had a recent moderate throbbing, with nausea and photophobia have also been weight gain (5-15%). reported.26 Thus, it is likely that the prevalence of IIH in the developed world will rise in parallel with that of In many cases, patients might also have a coexisting obesity.13 primary headache disorder, such as migraine or tension headache25and thus the headache does not always One of our patients was an eight-year-old female. With respond to treatments that decrease ICP. the exception of this child, all the other patients were between ages 20 to 40 years. Despite a high predilection Case 6 had a prolonged history of headaches spanning for obese young women, IIH can occur in children, older over a year. Considering the fact that her disc did not adults, and in non-obese persons of either sex.14,15 show signs of chronic papilloedema or atrophic changes, it is possible that she had a primary headache disorder. It In children, the annual incidence for symptomatic disease has been reported that back pain, neck pain and radicular is 0.9/100,000.14 It was previously thought that there was pain frequently occur27 and neck pain was reported in two no sex predilection in IIH among children however of our cases. Papilloedema is the most common sign at Balcer et al found that prevalence of IIH increased with presentation. It may be associated with peripapillary age. He found that children with IIH aged 3 to 11 years, haemorrhages, exudates, and macular oedema. 50% were girls, 12 to 14 years of age, 88% were girls, Papilloedema commonly results in transient ischaemic and in children older than 15 years, 100% were girls.16 obscurations (TVOs) which are due to transient ischaemia of the swollen optic nerve head. TVOs can The underlying pathogenesis of IIH is uncertain however present as brief episodes of monocular or binocular raised ICP is a uniform characteristic feature. It appears vision loss. Transient visual obscurations were that changes in the volume of blood, CSF and brain tissue experienced by 2 out of 6 of our patients (33.3%). This is influence intracranial pressure. IIH therefore likely lower than the 68% reported by Giuseffi et al.23 This may represents a disorder of CSF regulation, potentially be due to the fact that most of them may not have through CSF over secretion or impaired drainage. The understood the symptom of TVO and interpreted it as symptoms and signs in the only paediatric case in this blurred vision. case series was a preceded by a history of taking doxycycline for acne treatment. Doxycycline is a well- Fifty percent of our patients reported horizontal diplopia. recognized precipitant of idiopathic intracranial This is not a surprising finding since diplopia has been hypertension.17 Case 5 also had a history of using oral found to occur in one-third to two-thirds of patients with contraceptive pills which had been prescribed for IIH at presentation.28 It tends to be binocular and treatment of irregular menses. horizontal, as a consequence of abducens nerve palsy, and typically resolves with normalization of ICP. Factors such as medications (tetracycline and its derivatives, cyclosporine, lithium, nalidixic acid, Untreated papilloedema can progress to irreversible nitrofurantoin, oral contraceptives, levonorgestrel and vision loss and secondary optic atrophy in up to 31% of tamoxifen), endocrine abnormalities (such as patients28 and this is more likely to occur in men,8 black corticosteroid withdrawal, anabolic steroids, excessive patients7 and those with a fulminant onset of IIH.29 Visual growth hormone, and thyroid disease), vitamin A excess loss ranged from none to moderately severe in our 84 www.ghanamedj.org Volume 53 Number 1 March 2019 Case report patients. Pulsatile tinnitus has also been reported and this departments often leads to delays in getting the lumbar was experienced by three out of six (50%) of our patients. puncture with opening pressure measurement done. Other factors include lack of appropriate sized lumbar In developing countries diagnosis is particularly a puncture needles, difficulty in accessing manometers and challenge for several reasons. The first reason is failure a deficiency of medical personnel who are conversant to recognize the symptoms and suspect the disease. In with the use of manometers to measure CSF pressure. case 2, the patient was an 8 year old who had been Only 2 out of our 6 patients had their CSF opening experiencing the symptoms of headaches for 4 months pressures measured. The goals of management are to during which she had attended health facilities. It was improve the symptoms and preserve vision. It is only when she started experiencing diplopia that she was important to establish at the beginning whether there is seen at a facility where a Cranial MRI was requested and any precipitant or contributing factor, and remove it. the parents decided to report to the Eye Centre, KBTH for a second opinion. It was a similar occurrence in most Our 5th patient was on oral contraceptive pills at the time of the patients presenting to us. Majority were diagnosed of presentation and this was discontinued immediately. after 2 weeks of onset of symptoms. In the case of our paediatric patient, the doxycycline had already been stopped prior to presentation. Obesity or On presentation, it is essential to measure the patient’s recent weight gain are well known associations of IIH.13 blood pressure to exclude malignant hypertension.11None It has been observed that even a modest degree of weight of our patients had severe or malignant hypertension. loss (5-10%) is usually required for improvement in The initial weight must also be checked and documented. symptoms and signs.33-36 Optic nerve function must be assessed by testing visual acuity, pupillary responses and colour vision. The pupils Drug treatment should be dilated for optic nerve head and macula Acetazolamide, a potent enzyme inhibitor of carbonic examination. The level of papilloedema should be anhydrase, is currently considered the mainstay of documented as this helps in follow up. This has been pharmacological management in IIH. It works by made easier with the use of the Optical Coherence impeding the activity at the choroid plexus reducing CSF Tomography (OCT) which accurately quantifies the secretion. Piper et al, in a recent Cochrane systematic degree of optic disc swelling.30 Where not available the review identified two randomised control trials for the Frisen scale can be used to quantify degree of use of acetazolamide in IIH.37 Dosage is usually started papilloedema. The Frisen scale was used to grade the at 1-2g/day in divided doses. Most patients cannot level of papilloedema in our patients. tolerate high doses due to unpleasant side effects such as lethargy, nausea, altered sense of taste and paraesthesia. Brain imaging is key in excluding space-occupying All of our patients were started on oral acetazolamide. lesions and other causes of raised ICP as such as hydrocephalus and cerebral venous thrombosis, to make The dose range was 500mg-2g/day. Doses had to be the diagnosis of IIH.1 MRI/MRV is preferable to CT scan altered to suit the patient’s tolerability to acetazolamide. in making a diagnosis. Imaging abnormalities such as Case 5 experienced complete alleviation of symptoms on empty sella or flattening of the pituitary, tight 1.5g/day on acetazolamide however developed an subarachnoid spaces, flattening of the posterior globe, urticarial rash for which dose was reduced to 1g/day in 2 protrusion of the optic nerve head, enhancement of the divided doses interspersed with 2 doses of furosemide prelaminar portion of the optic nerve head, distension of 40mg. Topiramate has been reported to be efficacious in the optic nerve sheath, and vertical tortuosity of the optic relieving headache caused by IIH;23 however none of our nerve are associated with raised ICP are commonly patients was put on it. observed in IIH patients.31,32All our patients had neuroimaging however only one did an MRI scan which Surgery is the preferred form of imaging to diagnose IIH.32 Surgical procedures are usually required in patients with a fulminant onset of disease or when other treatments Lumbar puncture plays a significant role in the have failed to prevent progressive visual loss. Options management of patients with IIH. It is both diagnostic include optic nerve sheath fenestration or a CSF and therapeutic. In our setting however performing a diversion procedure, such as ventriculo/lumbo-peritoneal lumbar puncture and measuring opening pressure can be shunting. Ventriculo/lumbo-peritoneal shunting a challenging task for ophthalmologists, as they do not produces a rapid reduction in ICP, often with a perform the procedure themselves but have to refer subsequent improvement in symptoms and signs, patients to the neurology unit for the procedure The lack particularly headaches.38,39 Surgery was also not of a well-established rapport between the two indicated in any of our patients. 85 www.ghanamedj.org Volume 53 Number 1 March 2019 Case report 13. Daniels AB, Liu GT, Volpe NJ, Galetta SL, Moster CONCLUSION ML, Newman NJ, Biousse V, Lee AG, Wall M, In conclusion, IIH can no longer be described as a rare Kardon R, Acierno MD, Corbett JJ, Maguire MG, disease in our part of the world. As the prevalence of Balcer LJ. Profiles of obesity, weight gain, and obesity increases,12 clinicians must be prepared to see quality of life in idiopathic intracranial hypertension more cases of IIH. It is important to have a high index of (pseudotumor cerebri). 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