Following IIH diagnosis all patients were treated according to the IIH consensus guidelines with weight management advice and acetazolamide therapy where appropriate [1, 7]. The mean (SD) duration since the IIH diagnosis was 2.4 years (1.5). All cases presented with increased headaches at the time of initially elevated ICP and IIH diagnosis. Their headaches persisted, even after resolution of papilledema, and had migraine-like characteristics (photophobia, phonophobia, kinesophobia, nausea and throbbing pain) as is typically reported IIH headache [1, 4, 6]. All patients were adult, female with IIH in occular remission and chronic moderate/severe headaches (≥15 per month) that ≥3 prior conventional oral preventative treatments had failed (inadequate efficacy with appropriate dosing and treatment duration; intolerable adverse effects; contraindications preventing use ) and then suffered recurrence of papilloedema whilst on erenumab. In this cohort treatments that failed included tricyclic antidepressants, topiramate, propranolol, pizotifen, duloxetine, dosulepin and candesartan. These chronic migraine-like headaches were elibigle for treatment with the CGRP monoclonal antibody erenumab (Aimovig®, Novartis) within the National Health Service (NHS) headache service at University Hospital Birmingham NHS Foundation Trust, UK as part of a free of charge scheme (Novartis).
The pathway for erenumab delivery entailed a full headache and neuro-ophthalmology assessment prior to erenumab initiation, including optical coherence tomography (OCT) imaging and dilated slit lamp fundus assessment, which confirmed complete resolution of papilloedema (Table 1). Patients were then commenced on erenumab 70mg four-weekly subcutaneous injection after a 30-day pre-treatment period including headache diary evaluation. In all cases the headache response (improvement in monthly headache days and/ or severity) was greater than 30% but less than 50% and hence, as per the local pathway, the dose was increased to 140mg at 3 months. Patients were seen 3-monthly over a 12-month period. Erenumab initiation (after assessment of a 30-day pre-treatment period) and follow-up visits involved headache diary evaluation of monthly moderate/severe headache days (MmsHD) (moderate to severe headaches lasting >4 hours), all monthly headache days (MHD) (headaches of any severity lasting > 30 minutes), monthly analgesic frequency, headache severity, disability (Headache Impact Test -6, HIT-6) and IIH symptoms (Table 1). All patients had a stable course and substantial history of debilitating migrainous headaches prior to treatment initiation evident from the high burden of monthly headache days 12 months prior to treatment (Table 1).
A 42 year old woman first presented with severe increased headaches with visual obscurations, double vision, tinnitus and was noted to have papilloedema. The headaches had migraine-like characteristics. She had a past history of occasional episodic migraines, asthma and fibromyalgia and a family history of migraines. Her body mass index (BMI) was 33 kg/m2 and her LP opening pressure was 34cm CSF with no alternative cause of raised ICP on brain imaging (MRI Head and MR Venogram). A diagnosis of IIH was made  and she was commenced on acetazolamide (later stopped due to side effects) and advised to lose weight. The papilloedema resolved but debilitating headaches continued over the subsequent 12 months. Therapeutic trials of topiramate, amitriptyline and propranolol failed (pizotifen was contraindicated) and she was then commenced on erenumab. Headaches substantially improved (Table 2) but she developed worsening of her visual disturbances similar to that experienced at presentation and on review was noted to have a papilloedema relapse (her BMI had also increased) (Table 2). An LP revealed an opening pressure of 31cm CSF (followed by post-LP headache exacerbation for 1 week) and she was commenced on acetazolamide and advised to lose weight with subsequent improvement of papilloedema. Her headaches remained controlled throughout the following year despite the relapse of IIH (Table 2).
A 34 year old woman initially presented with increased debilitating headaches, blurred vision, visual obscurations, tinnitus and was noted to have papilloedema by the optometrist. The headaches had migraine-like characteristics. She had a past history of episodic migraine but no family history of migraines. Her BMI was at 49 kg/m2 (reported weight gain of 30kg over the preceding 5 years). After normal neuro-imaging, CT Head and CT Venogram (apart from radiological signs of raised ICP), she had an LP opening pressure of 34cm CSF. A diagnosis of IIH was confirmed  and she was commenced on acetazolamide and advised to lose weight. She developed side effects from acetazolamide, this was discontinued. Therapeutic trials of topiramate and amitriptyline failed (beta blockers and pizotifen were contraindicated) and her chronic headaches remained. Following weight loss her papilloedema resolved but migraine-like headaches persisted with similar frequency and severity for over 12 months and she was subsequently commenced on erenumab. Headaches then substantially improved (Table 2). During follow-up she reported weight gain and symptoms of visual disturbances. She was noted to have a papilloedema relapse (Figure 1). She was offered acetazolamide but declined and a referral to a community weight management program was made. Following further weight gain, after gall bladder surgery, her papilloedema further worsened and she underwent ventriculo-peritoneal shunt surgery to preserve vision. Her headaches since erenumab initiation remained improved despite the IIH relapse and shunt surgery.
A 46 year old woman presented with substantially increased headache symptoms, with migraine-like characteristics, and was noted to have papilloedema. She had a past history of episodic migraine for 20 years, depression but no known family history of migraine. Her BMI was 39 kg/m2 and no alternative cause of raised ICP on brain imaging (MRI Head and MR Venogram). LP recorded an opening pressure of 36cmCSF and a diagnosis of IIH was made . She was offered acetazolamide and advised to lose weight. Following weight loss, papilloedema resolved but her chronic migraine-like headaches remained consistently severe for at least 12 months (Table 2). Headaches did not improve with a therapeutic trial of amitriptyline. Other preventative therapies were contraindicated (topiramate and beta-blockers due to severe depression and pizotifen due to the risk of weight gain) and erenumab was commenced. Headaches substantially improved (Table 2), but she developed visual disturbances (obscurations) and was noted to have recurrent active papilloedema. She was commenced on acetazolamide and advised to lose weight. Headaches remained improved (Table 2) despite return of papilloedema.
A 24 year old woman first presented with worsening headaches and visual disturbances and was noted to have papilloedema with a BMI of 38kg/m2. The headaches had a migraine-like phenotype. She had a history of occasional tension type headaches, bipolar disorder and no family history of migraines. With no alternative cause of raised ICP on brain imaging (MRI Head and MR Venogram) an LP was performed revealing an opening pressure of 40cm CSF and a diagnosis of IIH was made . She had further LPs with similar opening pressures in the short term with no sustained headache improvement and was commenced on acetazolamide. At subsequent review her papilloedema was in remission and she had already stopped her acetazolamide due to side effects. She was, however, still suffering with ongoing disabling chronic migraine-like headaches for over 12 months since IIH diagnosis. Due to risk of deteriorating mood and weight gain topiramate and tricyclics/beta-blockers were contraindicated, respectively. Candesartan was also contraindicated due to postural vasovagal episodes and she was commenced on erenumab. Her headaches substantially improved (Table 2). Subsequently, visual obscurations returned and she was noted to have a relapse of her papilloedema whilst still maintaining the improvement in her headaches. She was offered acetazolamide, advised to lose weight and her papilloedema did not worsen. Her headaches remained in remission during the IIH recurrence.
A 36 year old woman, with a BMI of 41 kg/m2, initially presented with debilitating headaches, tinnitus and visual disturbances. The optometrist noted papilloedema. Headaches had a migraine-like phenotype. She had a past medical history of low mood, familial structural renal tract abnormalities and no family history or prior history of migraines. Following normal neuro-imaging, CT Head and CT venogram (apart from radiological signs of raised ICP), an LP was performed with an opening pressure recorded at 37cm CSF. A diagnosis of IIH was given  and due to the risk of renal impairment acetazolamide was not recommended and she was referred to a community weight management program which successfully helped her reduce her BMI to 30 kg/m2 with concurrent resolution of her papilloedema. Her chronic migraine-like headaches persisted over 12 months despite therapeutic trials of amitriptyline, topiramate, dosulepin and candesartan with inadequate efficacy or intolerable side effects. She was commenced on erenumab with a marked improvement in headaches (Table 2). Unfortunately her weight increased (to a BMI 42 kg/m2) and her papilloedema recurred. However, her headaches did not increase as they previously have when she initially presented with IIH (Table 2). She was again referred to a community weight management program which was successful in helping her reduce her weight and her papilloedema improved.
A 25 year old woman originally presented with marked worsening of headaches and tinnitus, papilloedema was noted. Her BMI was 35 kg/m2. The headache phenotype was migraine-like. She had a past history of episodic migraines, hypermobility, back pain, Raynaud’s syndrome, depression, low vitamin D and family history of migraines. No alternative cause of raised ICP was found on brain imaging (MRI Head and MR Venogram) and an LP was performed with an opening pressure of 35cm CSF and the diagnosis of IIH was made . She was given advice on weight loss and commenced on acetazolamide. Following successful weight loss her papilloedema resolved despite persistence of her chronic migraine-like headaches over 12 months. Due to resolution of papilloedema and associated side effects, acetazolamide was stopped. She had tried duloxetine for low mood with no effect on her persistent headaches. Due to risk of deteriorating mood and weight gain topiramate and tricyclics/beta-blockers were contraindicated, respectively and was commenced on erenumab. Headaches improved on erenumab (Table 2) but she then developed increasing blurred vision in the context of weight gain. On examination a relapse of papilloedema was noted. Acetazolamide was commenced and weight loss advice was provided. The headaches remained controlled throughout the IIH relapse.
A 25 year old woman (BMI of 31kg/m2) presented with disabling increasing headaches and papilloedema was noted. The headaches had a migraine-like phenotype. She did not have any significant past medical history and no family history of migraines. Neuro-imaging (MRI Head and MR Venogram) did not reveal an alternative cause of raised ICP and an LP recorded an opening pressure of 54cm CSF (followed by post-LP headache exacerbation for 1 week).A diagnosis of IIH was made . She was commenced on acetazolamide and advised to lose weight. Neither acetazolamide nor topiramate were tolerated and did not improve her chronic migraine-like headaches that remained over 12 months. Following weight loss, the papilloedema resolved but migraine-like headaches persisted. Due to risk of weight gain, tricyclics and beta-blockers were contraindicated and erenumab was initiated which improved her headaches (Table 2). At follow-up weight gain was noted and clinical examination revealed return of papilloedema. She was commenced on acetazolamide and advised to lose weight. Papilloedema subsequently improved. Her headaches remained controlled on erenumab despite the IIH relapse.
We have reported seven patients with IIH who had disabling long term headaches with migraine-like characteristics (mean (SD) IIH duration 2.4 (1.4) years) persisting despite complete resolution of papilloedema. Monthly headache burden was significantly reduced following initiation of a CGRP monoclonal antibody therapy (Table 2). Of principle interest here is the lack of headache symptoms when raised ICP retuned, as evidenced by recurrent papilloedema, whist they were taking the CGRP monoclonal antibody, despite headache being the dominant feature at initial IIH presentation and indicating exacerbations of IIH in the past. The relapse of IIH was identified at follow up due to patients’ describing minimal or subjective changes in IIH symptoms (blurred vision, double vision, transient visual obscurations, tinnitus) or weight gain (Table 1) which prompted slit-lamp examination and OCT imaging, which confirmed the recurrence of papilloedema (Table 2, Figure 1). Improved headache burden was also noted at subsequent time points despite ongoing papilloedema (Figure 1). Erenumab reduced the mean frequency of MmsHD by 38% at 3 months, 49% at 6 months, 63% at 9 months and 65% at 12 months compared to the 30-day pre-treatment period. There was a reduction in mean frequency in overall MHDs by 45% at 3 months, 30% at 6 months, 50% at 9 months and 42% at 12 months. There were no serious side effects of treatment reported at the 3-monthly assessments (over 12 months) and none of the patients withdrew from erenumab.