Case studies of Paget's disease

- Asymptomatic discovery and rare neurological complications

A case of Paget’s of the skull

A recent case study was published in the Journal of Clinical and Translational Research where the authors presented a case of a 60-year-old female in Pakistan, whose Paget’s disease was found when she was undergoing evaluation for gallbladder surgery. A blood test showed an alkaline phosphatase (ALP) of 1537 IU/L (normal range is between 30-130 although reference ranges may vary between laboratories). Her high ALP prompted further investigation and a bone scan revealed Paget’s disease in the skull, although she was asymptomatic at diagnosis. Clinical symptoms differ with the disease location; skull involvement usually causes the skull to enlarge, along with headaches and/or deafness. When the base of the skull is affected, it can lead to rare complications such as hydrocephalus.

The lady had a bisphosphonate infusion of 5 mg zoledronic acid. She was followed-up after three months at the rheumatology outpatient department, when a repeat ALP test showed markedly reduced levels down to 250 IU/L.

Early detection and management of Paget’s is important. While it might not initially present with symptoms, left unchecked, it can lead to severe complications. Therefore, it's crucial for healthcare professionals to thoroughly investigate any unusual blood test results, even in asymptomatic individuals. Staying vigilant and taking timely action can make a substantial difference in managing Paget's disease and ensuring better outcomes for those affected. A key goal of the Paget’s Association is to push for early diagnosis.

The authors point out the rarity of this disease in Southeast Asia. In conclusion, they remarked that isolated raised ALP levels should always be investigated to rule out asymptomatic individuals.

Reference
Ali M, Farooq O, Rafique Z, Farooq H, Iftikhar F, Malik M. A rare case of asymptomatic Paget's disease of the skull in a 60-year-old Asian female. Journal of Clinical and Translational Research. 2023 Jul 26;9(4):261-264. PMID: 37593243; PMCID: PMC10431192.

Epilepsy, a rare complication of Paget's disease

This case study from authors in Morocco underscores a critical but rare aspect of Paget's disease – its ability to occasionally manifest alongside unusual neurological symptoms, such as epileptic seizures. While the connection between Paget’s and headaches is more established, the occurrence of seizures, as illustrated in this case, is far less common and often poses a diagnostic challenge, particularly in older adults. The 75-year-old woman in this study presented with a history of chronic headaches that did not prompt a thorough investigation for Paget’s disease until she experienced tonic-clonic seizures (the type of seizure most people picture when they think about seizures). These had begun three weeks before admission at a rate of one every other day. An examination showed bulging of temporal veins, head enlargement and protruding forehead. The authors provide compelling evidence suggesting the patient's seizures were directly related to Paget’s affecting her skull. The epileptic activity seen on an EEG (a measure of electrical activity of the brain), was localised to the right frontal region of her brain – the same area where an MRI scan revealed the most significant bone thickening and compression. Despite being on anti-seizure medication, she experienced non-convulsive status epilepticus, suggesting an underlying, untreated cause. A bone scan showed Paget’s disease restricted to her skull and face. An x-ray of her skull showed a characteristic ‘cotton wool’ appearance and her ALP levels were high (536 IU/L).

Her seizures completely resolved after she received zoledronic acid, a potent bisphosphonate used to treat Paget’s disease. Her anti-seizure medication was subsequently tapered off without any recurrence of seizures. Comprehensive diagnostic tests ruled out other possible causes including infections, metabolic disorders, inflammation or tumours, further strengthening the link between seizures and Paget’s in this case.
While this case study sheds light on the potential for Paget’s to cause epileptic seizures, the exact mechanisms responsible for this association remain unclear. The authors propose that the same processes involved in Paget’s-related headaches might also play a role in seizure development. One such process is regional vascular steal syndrome where the increased blood flow to the Pagetic bone essentially "steals" blood from the surrounding tissues including the brain, potentially leading to ischaemia (reduced blood flow).

This case study serves as a crucial reminder to clinicians to consider Paget’s as a potential diagnosis in older patients presenting with neurological symptoms, even seemingly common complaints like chronic headaches. The delay in this case highlights a crucial point: the condition often mimics other conditions leading to delayed diagnosis and potential complications. Early recognition and prompt treatment with a bisphosphonate is needed to prevent rare debilitating complications like epileptic seizures, ultimately improving outcomes and quality of life.

Reference
Ouhabi D, Tibar H, Benomar A, Jiddane M, Regragui W. Headache and Status Epilepticus Reveal Paget's Disease of the Bone. Cureus. 2024 May 19;16(5):e60588. doi: 10.7759/cureus.60588. PMID: 38894759; PMCID: PMC11184908.