PFBC is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcifications in the basal ganglia. The calcifications may also occur in the dentate nucleus, thalamus, and cerebral cortex. Both nonfamilial and familial cases of PFBC have been reported, predominantly inherited in an autosomal-dominant fashion [5]. It may also be related to calcium and phosphorus metabolism and endocrine changes [7].
Previous studies has shown that changes of some genes, such as solute carrier family 20 member 2 (SLC20A2), platelet-derived growth factor receptor alpha (PDGFRB), platelet-derived growth factor subunit B (PDGFB), xenotropic and polytropic retrovirus receptor 1 (XPR1) and myogenesis regulating glycosidase (MYORG), are associated with the pathogenesis of PFBC [8]. The pathogenic changes of SLC20A2, XPR1, PDGFB and PDGFRB are the reasons for the autosomal dominant inheritance mode of the disease [9,10,11,12]. Furthermore, the biallelic mutation of the MYORG gene determines the cause of autosomal recessive PFBC [13, 14]. However, these genes can only explain less than half of all PFBC cases [8]. The patient's parents have no clinical manifestations or related diseases during the collection of medical history, which precludes the possibility of dominant inheritance. Next-generation sequencing or genotype testing was not performed in this patient, but according to previous studies, the CT images (no pontine calcification) and pre-admission conditions (no dysarthria, movement signs, etc.) do not support the patient as MYORG-mediated PFBC [15].
PFBC has a variety of clinical manifestations, predominantly with neuropsychiatric features and movement disorders [5]. Neuropsychiatric features include cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, schizophrenia-like psychosis, and personality changes [16, 17]. Other clinical features include parkinsonism, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis [18]. Interestingly, PFBC often begins with these clinical features, leading the patients to go to the hospital and therefore be diagnosed with PFBC. However, this patient did not have neuropsychiatric features and movement disorders as her primary manifestations.
Koutsis et al. reported a case of β-thalassemia major combined with PFBC [19]. In that case, long-term transfusions created iron overload, which may cause hypoparathyroidism in thalassemia patients [20]. Besides, previous studies have confirmed that hypoparathyroidism, infection and systemic lupus erythematosus can lead to the formation of calcifications. In our case, she had no history of anemia-related symptoms or blood transfusion, nor did she have any associated endocrine changes. She also did not have calcium, phosphorus, or trace elements metabolism changes. Although 25-hydroxyvitamin D changes and calcifications have been reported to cause intracranial calcification, vitamin supplementation is sufficient for menopausal women who have low levels of 25-hydroxyvitamin D [21]. Therefore, there might be other reasons for the formation of intracranial calcifications in this patient. Notably, this patient did not have endocrine changes, which may have led to her calcifications being smaller than in previous cases, and their small size might be why the patient had no clinical manifestations.
Previously reported literature may shed light on the possible consequences of vascular calcification in these patients. A 65-year-old female patient with PFBC was reported to have a rare site cerebral haemorrhage because of the massive calcification of cerebral blood vessels in the basal ganglia (the most common site of cerebral haemorrhages) that may have prevented the occurrence of hypertensive cerebral hemorrhage [22]. In a report of a 36-year-old male patient with PFBC and ischemic stroke, it was proposed that the underlying pathogenic process of PFBC may lead to extensive calcium and mineral deposits in diseased vessels [23]. Uygur et al. implemented intracranial blood flow testing in the patient and recorded decreased blood flow in calcified areas, which may have led to further focal ischemic changes [24]. Neuropathology has proved that calcifications are observed in the media of medium and small calibre arteries, arterioles, and capillaries in PFBC, leading to luminal obstruction [25]. Further research confirms that alcium-phosphate accumulation initiates in neurovascular unit (including neurons, astrocytes, microglia, pericytes and endothelial cells) in PFBC patients and mouse models [8]. Calcium deposits can be a double-edged sword since a certain degree of calcification may be a favorable manifestation of blood vessels, preventing bleeding. However, severe calcification can lead to obstruction of the blood supply.
Based on these findings, we speculate that PFBC may be due to the formation of abnormal intracranial vascular calcification, which leads to a decrease in blood flow in the calcified area. This then leads to ischemic manifestations in the calcified area and an increased likelihood of bleeding elsewhere. Further clinical cohort studies are necessary to confirm our speculation. Regarding β-thalassemia, the occurrence of β-thalassemia and PFBC is unclear, and there are very few reports. We need more cases to confirm the relationship between β-thalassemia and PFBC and the possible underlying mechanism.
Patients with PFBC may be complicated by hypertension and intracranial aneurysm and other related diseases. Existing examples and evidence have confirmed that abnormal vascular calcification can have severe effects on blood vessels. Although the related factors and causes are unknown, we should pay attention to the blood pressure and intracranial blood vessels of PFBC patients. If there are enough cases, further mechanisms research on cerebrovascular disease, cerebral blood flow, and PFBC-related factors should be conducted.
In conclusion, our case provides clear images of the relative positions of PFBC and a ruptured intracranial aneurysm. This is the first reported case of a patient with PFBC associated with aSAH, ICH, and β-thalassemia. For patients with PFBC, we should pay attention to their blood pressure and intracranial vascular conditions, especially when combined with hypertension and persistent headache or other related prodromal symptoms of cerebrovascular disease. The association between PFGC pathogenic genotype and thalassemia is a point that we should further explore.
