This case report highlights a possible consequence of damage to the left frontoinsular region. A 53-year-old woman with chronic obesity and headaches presented with seizure, leading to the discovery and resection of a large sphenoid wing meningioma. Postoperative brain imaging revealed loss of the left frontoinsular cortex and portions of the underlying white matter, claustrum, and striatum. Throughout her adult life, this patient had tried and failed to lose weight, but after surgery, she no longer desired to eat large meals, and without effort, her body mass index decreased from 38.6 (85th percentile) to 24.9 (25th percentile). Combined with previous research implicating the insular cortex in interoception, appetite, and drug-related urges, her reduced hunger and effortless weight loss after resection of the left frontoinsular cortex suggest that this region of the human brain may play a role in hunger-related urges that contribute to overeating.

© 2023 The Author(s). Published by S. Karger AG, Basel

Primary sensory areas for taste, pain, and temperature are located in the insular cortex [1, 2]. Beyond these primary sensory functions, the insula is implicated in multimodal integration of visceral sensations relevant to appetite. Given its wide range of complex associations, the insular cortex is also thought to play a role in conscious awareness [3]. Much of the insular cortex remains poorly understood – particularly the “frontoinsular area” identified by von Economo [4].

The left frontoinsular area is functionally connected to the anterior cingulate cortex and to an area of the brainstem where lesions produce coma [5], and tracing studies in rodents have identified direct axonal connectivity between these brain regions [6]. These findings led to the hypothesis that the left frontoinsular area is important for conscious wakefulness [5], but other information suggests that consciousness does not require the insular cortex [7, 8], and we are not aware of any published cases with selective destruction of the left frontoinsular cortex.

Such cases would help clarify whether this cortical area plays a role in consciousness or other aspects of human behavior. For example, some ischemic strokes involving the insular cortex eliminate smoking addiction [9, 10]. Here, we describe a patient with preserved consciousness after resection of the left frontoinsular cortex. This patient experienced an interesting analog to disruption of smoking addiction – a reduced urge to overeat that resulted in effortless and sustained weight loss.

The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see www.karger.com/doi/10.1159/000529533).

A 53-year-old woman presented to an outside hospital after a first-time seizure. Her husband was awakened by her convulsing for approximately 1 min, unresponsive, with eyes open. She also had urinary incontinence and a 20–30 min post-ictal phase. After a head CT revealed a mass in the left middle cranial fossa, she was transferred to our tertiary care hospital. On arrival, she was normothermic (36.6°C; 97.9°F) and hypertensive (157/119 mm Hg). Pulse rate (99/min) and respiratory rate (20/min) were mildly elevated. She had no complaints, and there were no abnormalities on exam except tongue trauma. No metabolic abnormalities were evident on routine laboratory studies. Brain MRI revealed a 3.5 × 4 cm extra-axial mass along the anterior clinoid process of the left sphenoid wing, with uniform gadolinium enhancement, plus vasogenic edema in the adjacent brain (shown in Fig. 1). She was treated with dexamethasone and underwent tumor resection 3 days later without complication. Histopathology revealed a benign meningioma, with prominent whorls and scattered psammoma bodies (WHO grade I), plus uninvolved adjacent brain parenchyma.

a, b Preoperative MRI (1.5 T field strength): axial post-gadolinium T1 (a) and axial T2 (b). c–f Postoperative MRI (3 T field strength). c Axial post-gadolinium MPRAGE. d Axial T2. e Coronal post-gadolinium T1. f Coronal T2. The postoperative images reveal loss of the left frontoinsular cortex, along with a portion of the white matter, claustrum, and striatum underlying this anterior-inferior subregion of the insula.

Postoperative recovery was uneventful. There were no unexplained deficits in arousal, and no other neurological deficits were identified. She was prescribed levetiracetam 500 mg, twice daily, as anti-seizure prophylaxis. In a clinic follow-up visit, she reported difficulty with memory and word-finding, as well as episodes of nocturnal vomiting (without nausea) that awakened her from sleep. Levetiracetam was tapered after 6 months.

Seven years later (age 60), she presented to an outside hospital after another nocturnal episode of convulsions and unresponsiveness followed by post-ictal lethargy. Examination identified a right lateral tongue laceration. She was discharged home without anti-epileptic drug therapy. Six months later, she presented to our emergency department after her husband observed another nocturnal seizure. On arrival, she had no complaints. Vital signs, examination, and laboratory studies were unremarkable. Brain MR imaging did not reveal any new abnormalities. A 1-h scalp electroencephalogram (EEG) revealed slowing and frequent (5–10/min) sharp transients in the left mid-temporal area. Levetiracetam was restarted at 500 mg, twice daily. In a neurology clinic visit the following year (age 61), no neurologic deficits were identified. Due to nightmares and mood changes, plus persistent left-temporal slowing and sharp waves on a subsequent EEG, the levetiracetam dose was increased slightly, to 750 mg. She has not had any more seizures, and neuropsychological testing did not identify any cognitive deficits.

In a follow-up visit (age 62), she mentioned that she had lost weight over the 8 years after surgery. Reviewing the electronic medical record confirmed a gradual decline in body weight, from 102 kg, in the ICU immediately after surgery (224.9 lbs, body mass index [BMI] 38.6 kg/m2), to 65.8 kg, in the neurology clinic 9 years later (145 lbs; BMI 24.9 kg/m2). This 35% weight loss (−36.2 kg; −87 lbs; −13.7 kg/m2) represented a fall from the 85th to the 25th percentile among adult women in our electronic medical record (Fig. 2) and among US women her age (“Anthropometric Reference Data for Children and Adults: United States, 2015–2018,” Table 4; available at cdc.gov).

She remembered enjoying food more and eating to excess before surgery. In particular, she recalled difficulty refraining from large meals, which led to regaining weight after efforts to lose weight (“I spent early college to after having kids heavy. Two different times, I lost a lot of weight then gained it all back.”). After surgery, however, weight loss was effortless (“I lost a substantial amount of weight and kept it off… I didn’t do any organized programs or anything. I always thought I was a pretty hefty eater... now, I could just do without.”). She no longer felt hungry early in the day and began setting reminders to eat (“I don’t feel like I’m at all hungry... I don’t have an appetite, really.”).

a Change in body weight (kg) over time. b Change in body mass index (BMI) relative to the local distribution. Blue bars in this histogram represent the BMI distribution of n = 362,794 adult female patients (18–80 years) in the University of Iowa Hospitals and Clinics (UIHC) electronic medical record. Red bars represent the histogram bins containing our patient’s initial postoperative BMI (38.6 kg/m2, 85th percentile) and most recent BMI (24.9 kg/m2, 25th percentile).

Now, she often does not eat until the afternoon (a granola bar). She must set reminders and make a conscious effort to eat earlier, before she gets “shaky” from hypoglycemia (she developed insulin-dependent diabetes with an elevated anti-GAD antibody titer, years after surgery). Neuropsychological examination did identify mild anxiety symptoms, but there was no evidence of clinically significant depression or anhedonia (Beck Anxiety Inventory score: 10; Beck Depression Inventory score: 11). While she no longer feels compelled to eat large meals, she still enjoys food, especially chocolate.

This case is interesting for two reasons. First, there was significant damage to the left frontoinsular cortex but no demonstrable neurological deficit (besides nocturnal seizures). Thus, despite its prominent connectivity to a brainstem region necessary for arousal [5], the left frontoinsular area is not required for consciousness. This observation is consistent with reports of patients who recovered consciousness after herpes simplex encephalitis despite extensive damage to the insular cortex [8], and our conclusion likely applies to adjoining portions of the anterior claustrum and sub-insular white matter that were resected along with the frontoinsular cortex (see Fig. 1).

Second, this patient experienced gradual and sustained weight loss, without effort. She attributed her weight loss to no longer feeling an urge to eat large meals – now, she can “just do without.” To stress the significance of this much weight loss, it is important to understand the likelihood of adult weight loss. In a study of nearly 100,000 obese women [11], fewer than 1% lost even 5% of their body weight at 1-year follow-up, and most regained weight over the following months to years. In contrast, our patient lost 35% of her body weight and has maintained this lower body weight for a decade. Rare patients do lose this much weight, but the process typically involves illness, bariatric surgery, or intense effort. In contrast, weight loss in our patient was uncomplicated and effortless. We propose that the explanation relates to the left frontoinsular cortex.

The frontoinsular cortex is defined by the presence of von Economo neurons [4], but the functions of these neurons and this cortical area remain largely unknown. In one study, 7 of 17 epileptic patients reported a persistent change in appetite after resection of the insular cortex, but their body weights did not change, and the effect did not localize to a specific insular subregion [12]. Studies identifying a loss of drug-related urges after ischemic strokes that involved the insula also did not localize the effect to a specific subregion [9, 10], and patients who stopped craving cigarettes did not report a change in appetite [9], raising the possibility that separate regions are relevant to drug- and food-related cravings. Our patient’s effortless weight loss suggests a clinically relevant function for the frontoinsular region in hunger-related urges that contribute to overeating and obesity.

Previous attempts to treat obesity using deep brain stimulation (DBS) or ablation have targeted the hypothalamus or nucleus accumbens [13], and our patient’s sustained weight loss highlights the left frontoinsular region as an attractive target for further investigation. This anterior region of the insular cortex sends profuse output to the nucleus accumbens [14], where electrophysiologic recordings in the human brain identified a low-frequency activity pattern specific to episodes of overeating and where DBS led to reductions in both overeating and body weight [15]. The left frontoinsular cortex may contain a critical node in the brain network responsible for hunger-related urges, and suppressing this network via implanted electrodes or surgical ablation could be investigated as an alternative to bariatric surgery in patients with morbid obesity that is refractory to conventional treatments.

This research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. The patient gave written informed consent to publish images and other information in this case report. In accordance with local and national guidelines, including those of the University of Iowa Institutional Review Board (https://hso.research.uiowa.edu/ui-investigator’s-guideirb-standard-operating-procedures), this retrospective review of patient data did not require ethical approval.

The authors have no conflicts of interest to declare.

NIH – National Institute for Neurologic Disorders and Stroke (NINDS): NS099425 (JCG).

NIH – National Institute for Neurologic Disorders and Stroke (NINDS): NS114405 (ADB).

The funder had no role in study design, data collection and analysis, decision to publish, or preparation of this manuscript.

Benjamin D. Reasoner and Joel C. Geerling drafted and edited the paper. Benjamin D. Reasoner and Joel C. Geerling drafted and edited the figures. Aaron D. Boes first identified this case and collaborated on writing and editing this report. Benjamin D. Reasoner, Aaron D. Boes, and Joel C. Geerling edited and approved the final manuscript.

All data analyzed during this study are included in this article except for private health data in our electronic medical record. Further inquiries can be directed to the corresponding author.

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