Auditory Hallucinations Associated With Paget’s Disease

“Ms. A,” a 56-year-old, right-handed woman with a past medical history of Paget’s disease and essential hypertension, was admitted to the neurology floor of our hospital for evaluation of an episode of slurred speech lasting for a few seconds. The patient was otherwise asymptomatic and denied any physical complaints at the time of her admission to the hospital. On further evaluation, the patient reported having auditory hallucinations for the past 2 years. These auditory hallucinations consisted of two or three voices of unknown people, conversing with each other and saying good things about her. She also reported recently feeling more anxious than usual, without any obvious new stressors in her life. She stated that she was diagnosed with Paget’s disease about 4 or 5 years ago. She denied any other symptoms of psychosis/mood disorder or use of any psychoactive substances. Her physical examination, including a neurological exam, did not reveal any significant findings other than mild memory impairment. Mental status examination revealed a calm, cooperative, and appropriately-behaving woman with euthymic affect and good insight and judgment. Her family history of neurological/psychiatric/Paget’s disease was insignificant. Her routine blood tests, including complete blood count, complete metabolic panel, and dementia work-up (TSH, B₁₂, folate level, HIV and rapid plasma regain test for syphilis), did not reveal any significant findings. MRI of the brain and EEG were also within normal limits. She was seeing a psychiatrist on an outpatient basis, who started her on paroxetine 20 mg/day for nonspecific anxiety symptoms, but she was not prescribed antipsychotics because the auditory hallucinations were not bothersome.

Paget's disease of bone (often simply called Paget's disease), or osteitis deformans, is the most common form of Paget's disease. It is a chronic disorder that typically results in enlarged and deformed bones.¹ The disease was named after Sir James Paget, the British surgeon who first described it, in 1877.⁴ The excessive breakdown and formation of bone tissue that occurs in Paget's disease can cause weakening of bones, resulting in bone pain, arthritis, bone deformities, and fractures. Paget’s disease-induced neuropsychiatric symptoms have rarely been reported in English literature. Even though a very few cases of psychotic symptoms (in the form of delusions) in Paget’s disease have been described, but none of these cases have reported the presence of auditory hallucinations. To our knowledge, ours is the first report of a case of late-onset psychotic symptoms with auditory hallucinations in a patient with Paget’s disease.

In the above-mentioned case, the factors pointing toward a diagnosis of psychotic symptoms caused by Paget’s disease include the late age at onset of psychiatric illness, the onset of anxiety and psychotic symptoms with mild memory impairment 2 years after diagnosis of Paget’s disease, and the patient’s good insight into psychotic symptoms. There have been previous accounts in the literature, which reported findings of memory impairment, depressive, and psychotic symptoms in the form of delusions,^5–7 but none of these cases have reported the existence of auditory hallucinations. Moreover, it is worth mentioning that there is a syndrome of inclusion-body myopathy associated with Paget’s disease of the bone (PDB) and/or frontotemporal dementia (IBMPFD), characterized by early-onset PDB, premature frontotemporal dementia (FTD), and adult-onset proximal and distal muscle weakness clinically resembling a limb-girdle muscular dystrophy syndrome. IBMPFD can manifest in the form of psychotic symptoms and cognitive impairment along with the physical manifestations of Paget’s disease, as in our case. The pathophysiology behind IBMPFD involves a mutation in VCP (valosin-containing protein, resulting in a mutant form), which acts as an ATP-binding protein involved in vesicle transport and fusion.⁸

The mechanism by which Paget’s disease results in neuropsychiatric symptoms is still not clearly understood. A possible hypothesis proposes that the enlarging, deformed Pagetic bone can cause pressure on the brain, spinal cord, or nerves, thereby reducing blood flow to these areas of the brain and spinal cord, and also by affecting the physical conformation of the skull and vertebral column.⁷ Manifestation of neuropsychiatric symptoms in Paget’s disease remains rare.^7,8 Wyllie has maintained that the nervous system is rarely affected because the spatial capacity of the cranium actually increases with disease progression. However, psychiatric symptoms may arise when the vertical measurements, especially around the foramen magnum, are decreased and the neural foramen is narrowed.⁸

In conclusion, the existence of neuropsychiatric symptoms secondary to Paget’s disease is an underrecognized diagnosis, and clinicians should consider it a possibility whenever they encounter a late-onset, atypical presentation of neuropsychiatric symptoms in Paget’s-disease patients. Treatment of Paget’s disease may improve these symptoms without the need for long-term psychotropic medications.

Funding: None