Neuropsychiatric manifestations due to metabolic and structural dysfunction: two cases of hyperostosis frontalis interna

Hyperostosis frontalis interna (HFI) is a medical condition defined as abnormal bone growth on the posterior (internal) aspect of the frontal bone which is possibly a metabolic bone disease with significant clinical consequences particularly in postmenopausal women. While the etiology of HFI is not clear yet, it is frequently associated with other metabolic and endocrine conditions [1]. We are reporting on two patients who have HFI alongside secondary hyperparathyroidism caused by chronic kidney disease (CKD). Both patients showed significant neuropsychiatric manifestations, specifically tactile hallucinations and somatic delusions localised on their frontoparietal area.

Case 1: An 80-year-old female patient with hypertension presented with CKD with creatinine 1.30 mg/dL, eGFR 38.1 mL/min, urea 68 mg/dL, calcium 8.7 mg/dL and elevated PTH (82 pg/mL), confirming secondary hyperparathyroidism related to her kidney disease. Additionally, her hemoglobin level was 8.1 g/dL, which was consistent with anemia of chronic disease. In mental state examination; she exhibited agitation, insomnia, and somatic delusions paired with tactile hallucinations described as the sensation of dust pouring over her forehead to her face. Cranial CT imaging showed cerebral atrophy, dense nodular calcifications near the falx cerebri and HFI. Minimental state examination (MMSE) showed mild cognitive impairment with a score of 23. She was fully oriented and delirum was not considered with normal EEG recording.

Case 2: A 74-year-old female with a history of hypertension and CKD presented with the sensation of insects on her head. Laboratory tests revealed an eGFR of 34 mL/min, creatinine of 1.57 mg/dL, and urea of 40 mg/dL. Her metabolic profile also showed secondary hyperparathyroidism with a PTH of 74 pg/mL (14–72), calcium of 8.6 mg/dL, phosphorus of 2.9 mg/dL, and Vitamin D at 19.3 ng/mL. Additionally, her hemoglobin was 9.9 g/dL consistent with anemia of chronic disease. The patient reported tactile hallucinations of insects crawling and itching, particularly around her frontoparietal area and developed somatic delusions that insects had entered her brain through her ears. Her orientation was intact, she exhibited a cognitive (MMSE) score of 22, indicating mild cognitive impairment. Brain CT revealed cerebral atrophy and significant HFI in the frontoparietal region, while an EEG showed irregular fronto-temporal slowing.

Discussion: Both patients exhibit a similar, syndromic presentation. The observed intense tactile hallucinations and somatic delusions were evaluated as a result of a triad of CKD, secondary hyperparathyroidism, and HFI. Uremia and calcium-phosphorus imbalance in the context of CKD may impair neuronal excitability, triggering hallucinations, while HFI adds a structural dimension to this process. It is hypothesized that the local suppressive effect of HFI on the frontal cortex and dura mater irritation may lead to frontal‑predominant neuropsychiatric symptoms, especially executive dysfunction, working memory deficits. Impairment in the executive functions, in turn, predisposes to the misinterpretation of these faulty perceptions and their eventual transformation into persistent somatic delusions [2,3]. These cases highlight the importance of a holistic evaluation of metabolic, endocrine, and structural findings in the differential diagnosis of newly onset neuropsychiatric symptoms in the elderly.

References

1.Alvarez, L., Corrigan, W., McGonegal, et al (2024). The clinical manifestations of hyperostosis frontalis interna: A qualitative systematic review of cases. Clinical Anatomy, 37(5), 505–521. 2.de Zubicaray, G. I., Chalk, J. B., et al (1997). Deficits on self ordered tasks associated with hyperostosis frontalis interna. Journal of Neurology, Neurosurgery, and Psychiatry, 63(3), 309–314. 3.Topaloğlu, Ö., Bayraktaroğlu, T., Tekin, et al (2022). Hyperostosis Frontalis Interna. Turkish Journal of Endocrinology & Metabolism, 26(4), 213–216.