The University of Iowa
Department of Neurology and Department of Ophthalmology and Visual Sciences
Idiopathic intracranial hypertension (IIH) is a disorder of elevated intracranial pressure (ICP) of unknown origin. Although it can affect any age and gender, it is classically seen in obese or overweight women of childbearing age . As per the modified Dandy criteria , IIH is defined by signs and symptoms suggestive of elevated ICP, including severe headaches and vision loss, in the absence of neurologic deficits (although cranial nerve VI palsies may occur) and with elevated ICP in the context of normal neuroimaging and cerebrospinal fluid analyses . These criteria must be fulfilled without another reasonable explanation for the elevated ICP .
Although uncommon overall, the incidence of IIH is on the rise. As of this writing, the overall incidence of IIH is approximately 2 per 100,000 , which is an increase from approximately 1 per 100,000 in 1988 [4,5]. This rising incidence likely reflects the continuing upward trend in obesity worldwide. According to the WHO global database on body mass index (BMI), 32.6% of US adults were obese in 2014, a dramatic increase from the 11.6% of US adults who were reported to be obese in 1990 . Although other known risk factors and systemic disease associations exist, weight remains the primary risk factor for IIH. The rates of obesity among patients with IIH have been examined in several studies worldwide. A retrospective study from Detroit Medical Center determined that more than 90% of IIH patients are obese [5,7]. Similar literature exists worldwide, with another study from Israel reporting that 97.2% of IIH patients were obese [7,8]. A study done in the UK demonstrated that the incidence of IIH in obese women was 11.9 per 100,000 . In another study of obese US women being evaluated for bariatric surgery, the incidence has been reported to be as high as 323 per 100,000 . In contrast to absolute weight alone, IIH is also associated with recent weight gain, as seen in a study of newly-diagnosed IIH patients, which found an increased risk of IIH among those who had gained 5-15% of body weight in the 12 months prior to diagnosis. Interestingly, this risk was present in both obese and non-obese patients, indicating that the pattern of weight gain may also be important factor in developing IIH [5,11].
The mainstays of treatment for IIH include lifestyle modification, medical (acetazolamide, diuretics), and surgical (cerebrospinal fluid shunting, optic nerve sheath fenestration, bariatric surgery) therapies.
Establishing the role of weight loss in IIH began with the work by Newborg in 1974. This research showed that a low salt, fluid restricted diet consisting solely of rice could result in rapid weight loss and alleviation of all IIH symptoms; all 9 patients in this study showed improvement with this intervention . Unfortunately, the most important outcome measure for IIH trials, visual field function, was not measured. A growing body of literature supports the ubiquitous role of weight loss in the treatment of IIH. A retrospective study conducted by Johnson et al in 1998 demonstrated that a 6.2% weight loss in IIH patients is associated with resolution of papilledema (three-grade change in the Frisen scale) [1,13-15]. This study also demonstrated that the degree of weight loss was correlated with the amount of papilledema resolution, with a 3.3% weight loss corresponding to only a one-grade change in papilledema . Results similar to the work by Johnson have been reproduced, including a similar report by Kupersmith et al, which found that IIH patients with a weight loss of 2.5 kg during a 3-month period experienced more rapid improvements in papilledema and visual field testing when compared with those who did not lose weight . This study further supports the notion that the rate of weight loss is also an important factor in the treatment of IIH. A prospective study by Sinclair et al analyzed weight loss by placing women with IIH on a low energy diet. The intervention was divided into 3 stages, each lasting 3 months: no intervention, low calorie diet (425 kcal/day), and a follow-up period. The results showed that subjects who complied with the low energy diet for 3 months experienced weight loss, improvement of visual function, headaches, papilledema, ICP, and also experienced a reduction in analgesic use; these changes were also observed after cessation of the diet in the follow-up period . Perhaps most compelling, however, are the results of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT), a randomized, controlled trial examining the effects of acetazolamide on visual field function in IIH patients with mild visual loss . Compared to controls, the acetazolamide group experienced significant increases in weight loss (6% versus 3%) as well as improvements in visual field function, CSF pressure, papilledema grade, and quality of life measures in IIH . Results from the IIHTT continue to demonstrate the crucial role that weight loss plays in the treatment of IIH, while also offering a potentially exciting step forward in the standard of care for IIH via the adjunctive benefit of acetazolamide in treating the visual symptoms that patients experience .
Similar to the outcomes seen from weight loss by lifestyle modifications, weight loss via bariatric surgery offers complementary benefits for certain subsets of patients. A study by Sugerman found that bariatric surgery had a higher success rate in resolving IIH symptoms compared to CSF peritoneal shunting in severely obese patients (pre-operative BMI average of 47), with symptom resolution in all but one patient within 4 months of surgery . This surgery also offers the benefit of resolving a number of comorbidities associated with obesity, including hypertension, diabetes, degenerative joint disease, sleep apnea, and gastroesophageal reflux disease . A systematic review of 17 publications discussing bariatric surgery in IIH patients demonstrated an improvement in headache symptoms (92% of patients), visual field improvements (93% of patients), resolution of pulsatile tinnitus (88% of patients), and resolution of papilledema (100% of patients) . Bariatric surgery should be discussed and considered for all IIH patients who are morbidly obese (BMI > 40) as the results of long term dietary management in this demographic are poor.
According to a case-control study by Ko et al, 26/50 patients had a higher BMI at the time of symptom recurrence than at initial diagnosis (+2.0 BMI) when compared to patients without recurrence (-0.75 BMI) . Interestingly in this study, the average BMI of patients without recurrence was higher than those with recurrence at all points of observation during the study . The average percentage change in body weight between patients with and without recurrence was 6% and 0%, respectively, between initial resolution and recurrence . These results lend support to the argument that the relative weight gain is more crucial to recurrence than absolute weight gain or baseline weight.
There is a surprisingly sparse amount of data regarding who is most effective at counseling patients about weight loss; specifically, no body of evidence exists that directly compares patient weight loss outcomes between physicians and non-physician providers. However, there is no shortage of literature which consistently demonstrates that obese and overweight patients who receive advice from physicians have a statistically significant effect on weight loss versus those who do not [22,23]. This significant effect is mediated by both patient engagement in weight loss efforts as well as with absolute weight reduction . As a result of the consistent results on this subject, numerous guidelines recommend that physicians and primary care providers should counsel their overweight and obese patients on weight loss . Moreover, a great deal of research has examined the effect of multidisciplinary teams in weight loss. One review concluded that primary care physician led weight loss with the utility of auxiliary health care providers (e.g., lifestyle coaches) had a statistically significant effect compared to physician counseling alone in treating obesity in the primary care setting .
With regard to specific weight loss strategies, personalized weight-management plans are pivotal. The first step needed to create these plans is to assess for obesity-related risk factors including: stressful life circumstances, physical and mental issues, drug and alcohol use, medications that induce weight gain, eating disorders, prior attempts at weight loss, current diet and exercise habits, and the actual willingness to adopt a weight loss plan [25,26].
2013 Guidelines for the Management of Overweight and Obesity in Adults :
Using "patient-centered language" and shared decision making may be the most effective way that physicians can engage with patients in long-term weight loss solutions . Patient-centered language involves using non-judgmental language to describe weight and weight gain and focusing on the overall health impact that results rather than the physical appearance of weight gain. Shared decision making allows patients to dictate the goals of care and weight loss interventions. From a physician standpoint, it is crucial to develop trusting relationships with patients that are empathetic and encouraging to their individual circumstances.
One specific example of a patient-centered communication weight loss strategy is motivational interviewing, which entails four steps: engaging the patient in a non-medical conversation about weight loss, focusing on a specific change, eliciting a reason to change from the patient, and planning the actual intervention to change [25,28]. In this strategy, a patient-centered conversation somewhat removed from medicine guides the conversation with the goal being to engage the patient in such a manner that they outline their own weight loss plan. The role of the physician may be most effective when merely offering suggested options and letting the patient decide what would be best for them.
When assembling a personalized weight-loss plan for a patient, it is important to consider their current medication regimen and assess for any medications that are associated with weight gain and whether or not they can be substituted by a medication that will not affect their weight, or, which may even facilitate weight loss. For instance, a number of commonly-prescribed migraine, diabetic, and psychiatric drugs are associated with weight gain .
The major goal of behavioral intervention is to modify diet and lifestyle in order to create a negative energy balance. Three recommended dietary approaches to achieve a negative energy balance include a general caloric restriction (1,200-1,500 kcal/day for women 1,500-1,800 kcal/day for men), prescribing a 500-750 kcal/day energy deficit, and restricting certain types of foods (high carbohydrate, high fat, low fiber) [25,27]. Physical activity recommendations aim for moderate-to-vigorous activity for >150 minutes per week, preferably 30 minutes daily [25,27]. Used in combination, these two strategies are highly effective weight loss tools . Specific strategies to adhere to these guidelines include self-monitoring and avoiding triggers to unhealthy eating, like stress and sleep deprivation .
According to the 2013 Guidelines, it is recommended that patients follow-up in person with a trained obesity-specialist at least twice monthly . However, it is important to note that the effectiveness of these behavioral interventions is often not transferrable from the specialist setting to that of primary care . According to a 2014 review by Booth et al, behavioral interventions in the primary care setting have a clinically insignificant effect at 12 and 24 months (<5% reduction in body weight) .
One promising behavioral intervention that can be utilized in the primary care setting is the 5 A's model. This model is derived from the National Cancer Institute's model for smoking cessation . Although several iterations exist, the version endorsed by the USPSTF consists of the following 5 A's: Assess, Advise, Agree, Assist, and Arrange . With regard to the specific components, patients particularly like physicians to help "Assist" and "Arrange" (provide adjunctive support, referrals to dieticians/specialists, etc.) . Other components generate more controversy, especially in regard to those that require physician's to identify that a patient has a weight issue, and thus can be perceived by patients as passing judgment . At present, the utility of the model is highly variable as is the data that supports it. More systematic research, including randomized controlled trials, will have to be conducted to ascertain the merit of the 5 A's model .
The use of technology-based behavioral weight loss solutions has also been shown to be effective . Interventions in this category generally have 5 key technical components: self-monitoring, counselor feedback and communication, group support, and use of a structured and individually-tailored program. Interventions that used a combination of at least 4 of these components led to significant decreases in weight compared to controls . These specific interventions are typically internet or smartphone-based and involve feedback support through communication modalities as simple as text messaging or Facebook messaging . Features such as these actually contribute to fairly high adherence rates to treatment plans . However, it is important to note that many technology-based weight loss options exist, and data regarding which specific solutions are optimal is still inconclusive . In a pilot study by Choo et al, a specific technology-based solution involving use of a mobile app and linked accelerometer for a clinic-based weight loss program was evaluated. While the researchers in this study found that their technology-based intervention could be a useful tool for weight management from the standpoint of usability and adoption, it was found to negatively impact the doctor-patient relationship . This finding indicates that a lot of work remains to be accomplished in order to optimize the social construct of communication between patients and physicians in the setting of technology-based weight loss solutions.
Lastly, due to the poor long-term outcomes of dieting (i.e., weight management resulting in dealing with significant periods of hunger during the day), patient education is very important. This includes counseling patients to eat only when hungry, to stop eating when full, and on "eating smart" (i.e., choosing non-processed foods with a high percentage of foods of high volume and low caloric value, such as fresh foods and vegetables). Meals should contain items that provide a feeling of satiety so that one is not hungry after several hours, and not necessarily chosen for low caloric value. An example would be adding avocado to salads or sandwiches.
Traditional dieting also involves limiting consumption to small portions or special kinds of food in order to lose weight and may lead to a feeling of hunger for substantial periods during the day. While this is sometimes a successful short-term strategy for weight management, it is a poor long-term strategy. The optimal weight for a person is not only measured by pounds or BMI. A healthy weight may very well be better defined in terms of fitness (adequate exercise), % body fat and healthy eating habits. Our Neuro-ophthalmology division at the University of Iowa has devised principles that lead to a healthy weight. These are the "Ten Commandments" of weight management:
One should think "make good choices" and not "diet." Instead of starving oneself for periods of time, choose foods that allow you to fill up on fewer calories. These are foods that are unprocessed, high in fiber, and low in fat and sugar. Examples include: fruits, vegetables, cooked whole grains such as barley, oatmeal, whole-wheat products and brown rice, and legumes. For protein, pick leaner cuts such as the white breast meat of poultry (without skin), pork loin, lean beef, legumes, and seafood.
Pharmacologic weight loss treatments are intended to be used by patients on low-calorie diets and increased exercise regimens . In order to be considered eligible for weight loss medications, patients must meet three criteria: failed weight loss goals by behavioral intervention alone, have a BMI ≥ 27 with a weight-related health problem or BMI ≥ 30, and must not be pregnant or trying to become pregnant [25,27]. Regarding the first of these criteria, weight loss goals should be ≥1 pound of weight loss per week in the 1st month intervention and >5% body weight within the first 3-6 months [25,27]. Orlistat (Xenical, Alli), lorcaserin (Belviq), phentermine/topiramate (Qsymia), naltrexone/buproprion (Contrave), liraglutide (Saxenda), diethylpropion (Tenuate, Tenuate Dospan), phentermine (Adipex-P, Suprenza), benzphetamine (Didrex), and phendimetrazine (Bontril, Bontril ER) are all FDA-approved weight loss drugs. Selecting the most appropriate drug for a given patient depends on a number of factors related to the side-effect profiles, mechanisms of action, cost and weight loss interval, and the maximal duration of use of these weight loss drugs. Orlistat, for example, is a generally safe and effective drug, but only confers patients with modest weight loss over an extended period (approximately 4 years of use to achieve its maximal effects) . Conversely, phentermine/topiramate gives patients up to a 10% reduction of body weight within one year, but at the cost of a fairly serious side effect profile (sympathomimetic, impairs cognition, causes depression, teratogenic) [34,35]. The sympathomimetic amines, benzphetamine, diethylpropion, phendimetrazine, and phentermine, are examples of short-term drugs that can only be used for 12 weeks . If a patient has lost <5% of their body weight within 3 months of treatment, a medication switch should be considered, possibly to a drug approved for long-term use . As discussed previously, acetazolamide offers a unique combination of weight loss and improved symptoms in IIH . However, the shortcoming of this therapy is that it does not result in lifestyle changes that are important for long-term appropriate weight maintenance. This is particularly crucial in the treatment of IIH where fluctuations in weight may actually be more detrimental to the individual [5-11].
Eligibility for bariatric surgery includes BMI ≥ 35 with weight-related health problems or BMI ≥ 40 and failure of nonsurgical weight loss interventions [27,36]. An important pre-surgical consideration is to assess for the likelihood of post-operative compliance (maintain follow-up appointments and adhere to post-operative medication and treatment plans). Surgical options include Roux-en-Y gastric bypass, sleeve gastrectomy, and gastric banding . These three procedures are associated with 32%, 25%, and 17% unadjusted reductions in body weight at 1 year, respectively . Accounting for the effects of lifestyle weight loss interventions, gastric bypass and sleeve gastrectomy have 22% and 15% reductions in body weight at 1 year . For patients with BMI ≥ 50, biliopancreatic diversion with or without duodenal switch are occasionally used .
In managing IIH patients at the University of Iowa, we employ the strategies outlined above. This entails a combination of education regarding making good choices (such as following the Ten Commandments of Weight Management), motivational interviewing, and education regarding the danger of blindness from IIH if not properly treated. This approach often results not only in optimal treatment of IIH, but also improved overall health.
Batra R and Sinclair A. "Idiopathic intracranial hypertension; research progress." J Neurol. 2014 Mar; 261(3): 451-60.
See related article Wall M. "Idiopathic Intracranial Hypertension (pseudotumor cerebri)." EyeRounds.org. 2015. Available at http://eyeRounds.org/article/IIH/
Batra NV, Parekh PK, Wall M. Weight Management in Idiopathic Intracranial Hypertension: A Tutorial. EyeRounds.org. July 28, 2016; Available from: http://EyeRounds.org/tutorials/Weight-management-IIH.htm