Aims

The aim of this study was to clarify the psychological and social characteristics of patients with primary brain calcification who have PDGFB pathological variants. In addition, we attempted to reveal, in particular, the experience of living with various symptoms.

Design

The qualitative study design that describes and summarizes phenomena as they are in daily language was used to clarify experiences of people living with a rare intractable disease [13, 14].

Participants and recruitment

Five patients over the age of 20 participated in the study. Each provided written, informed consent. Four of the patients were referred to a specialist, and one looked up information on the internet to see a specialist. Prior to the study beginning, PDGFB variants had been already discovered by the genetic study with the approval of the Ethics Committee and with written consent from the participants [11, 15].

Data collection

After introducing herself, one researcher, who has taken interview training, made a request for verbal and written informed consent. After obtaining consent, she conducted semi-structured interviews. At this time, she also received consent from each patient for her to obtain medical information from doctors. She secured a quiet place where privacy could be kept and recorded the interviews on an IC recorder with permission. While emphasizing the freedom to talk about experiences of the illness, she guided them to talk about their thoughts regarding: "how the illness was found", "thoughts when they first heard the name of the illness", "current thoughts about the illness", "thoughts for the family after the diagnosis", “what they learned through their experience with the illness”, and “what they hope for medical care and support systems.” The interviews were performed from March 2017 to February 2020. During this period, 3 out of 5 patients were able to undergo two interviews.

Analysis

Verbatim transcripts were made and qualitative content analysis was performed according to the qualitative method by U. Flick [16]. These verbatim transcripts of the interview, recorded on an IC recorder were done on paper, and the accuracy of the contents was confirmed among the collaborators. After that, (1) the verbatim record was put into MAXQDA10, a qualitative data analysis support software, and the record related to the theme was divided into groups and given names to express the meanings (coding). (2) All the codes were sorted and organized in chronological order. (3) All the codes were compared with each other and summarized by those with similar characteristics. A name indicating the characteristics was given to each group (subcategorization). (4) The passage of time was confirmed for all subcategories, and the subcategories were reassembled in chronological order. (5) Finally, the entire subcategory was reviewed again, compared with each of the other subcategories, summarized by those with similar characteristics, and the names indicating the characteristics were given to the grouped items (categorization).

In order to ensure the quality of the analysis results, we were supervised by collaborators specializing in qualitative research. Moreover, in order to confirm whether the interpretation of the interview data was appropriate, the results were given back to the participants, and a check by researchers was performed [17].

Ethics approval and consent to participate

The studies were approved by the Ethics Committees of Toyama Prefectural University (approval number: H29-14), Gifu Pharmaceutical University (approval number: 1–25 and 1–26) and Gifu University (approval number: 29–245 and 27–298). The studies were also registered in the University Hospital Medical Information Network (UMIN)-CTR System approved by the International Committee of Medical Journal Editors (ICMJE) (Registered ID; UMIN000022167 and 000030100).”

Outline of participants

There were 5 participants in the study: 3 females and 2 males (Table 1).

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Table 1. Summary of participants with PDGFB variants.

https://doi.org/10.1371/journal.pone.0275227.t001

The clinical manifestation and laboratory data of the participants were described in detail elsewhere [11] except ID3. The summary of the patients is also shown Table 1 and below.

Case ID1 is a mother of five children. ID2 is a daughter of ID1. They both had calcification in their brains and had the same pathological variants (c.457-1G>T). ID1 has suffered from headaches since she was 15 years old and had sometimes taken sedatives. Although no other special symptoms and signs were observed, recently she complained of forgetfulness without cognitive decline in examinations.

ID2 is a daughter of ID1. She visited an emergency unit in a hospital owing to headaches and pain in the back of her eyes that had continued since she was 10 years old. Two years later, she was sometimes unable to walk straight, then would recover. When she (ID2) was found to have PDGFB pathogenic variant, her mother (ID1), was also revealed to have the same variant. The data in details in ID1 and ID2 are shown as I-2, and II-2 (Case 2) in family 1, respectively, in the reference [11].

ID3 is a new sporadic case showing a pathological variant (c.196C>T, p.Arg66Cys (Supplementary data 1)). She had a simple head injury at the age of 19 and calcification was identified by a CT scan, according to her medical history. At the age of 38, she visited Gifu University hospital due to severe headaches. Her main complaint was headaches that had continued since her teens. She showed normal physiological examination without mental impairment. Her clinical examination studies showed no specific abnormality except calcification in the brain. ID4 is a sporadic case showing a pathological variant in PDGFB gene (c.33_34delCT, p. Cys12 Leufs*19). He had felt unstable going down the stairs for about a year, which led to his consultation. At the time of his first visit, the Mini-Mental State Examination (MMSE) score was 23 points. Mild tremor of his fingers and mild bradykinesia were also observed at the same time. His family has not been examined. His data are shown in detail as Case 3 in sporadic cases in the reference [11]. ID5, like his father, had calcification in the brain. His main complaint was difficulty speaking and forgetfulness. His neurological examination revealed 28 points in MMSE (almost normal mental activity) and mild cerebellar ataxia. His son was also tested owing to a panic disorder since his teens. He was found to have the same PDGFB variant as his father. However, as his mother did not want her son to be interviewed, no interview was performed. His data are shown in detail as Case 8 (II-2 in family 1) in the reference [11].

The ages of the participants at the time of the interviews were between 21 and 76 years. It had been 3 to 8 years since they were told that they were suffering from Fahr’s disease or IBGC. Interviews were conducted 1 or 2 times. Interview duration ranged from 32–68 minutes. ID4 was accompanied by his wife who worried about his forgetfulness. She said nothing during the interview.

Experiences of the patients who were told they suffer from a rare familial disease

As a result of content analysis, 7 categories, 15 subcategories, and 129 codes were extracted. Below, the categories are indicated by [], the subcategories are indicated by << >>, and the narratives are indicated by "".

Experiences of the patients who were told they suffer from a rare familial disease

Advanced skills are required to diagnose intractable neurological diseases for which there is no cure yet. If not done properly, it can cause psychological damage for patients [18]. Participants in this study with the PDGFB variants were told by specialists the name of this disease, which they had never heard of before, except for one patient (ID5). ID5 had lived with his father who had similar symptoms, and explained that the disease had no cure yet. All other patients were confused when they heard the diagnosis. Psychological support is crucial when announcing the name of a disease because patients may feel the need to make unnecessary decisions like one patient who accepted death, and another, who had an abortion in order to prevent the child from having the same fate. After several years, they realized that the disease was not a life-threatening illness because their CT images at the regular check-ups showed the calcified areas were not growing. However, they also experienced symptoms such as continual headaches, progressive forgetfulness, and small steppage gait. Then, it became clear in the study that anxiety about the future continued. One patient (ID1), especially, who was in the child-rearing period, had to work and needed to take notes to combat her forgetfulness and take painkillers so as not to bother others in her workplace. She had a strong desire not to let people in the workplace know about her illness. This led to anxiety, insomnia, and more severe headaches. In addition, in the current situation where there is no cure and the symptoms cannot be alleviated, the following psychological burden is put on the patients: They fear losing their job due to others knowing about the disease, and/or fear of being discriminated against or prejudiced as persons with a familial intractable disease. Moreover, when ID1 saw her child complaining of a fall or headaches, she was worried that her daughter might have inherited it.

A systematic review [19] of FIBGC reported that headaches are more common in PDGFB (32.5% of cases), and parkinsonism is more common in SLC20A2 (21% of cases). The review also found that cognitive impairment is more common in 15% of all cases and depression in 7% of all cases. In the present study, it was repeatedly stated that patients with PDGFB variants suffer from headaches such as "pain from heartbeats" and "temple tightening" from a young age, and even analgesics do not relieve these symptoms. In contrast, in six patients with the SLC20A2 variants that Batla reported in 2017, it was said that "headaches are relieved by oral medication, so it was not necessary to talk to a doctor about them [19]. Very recently, we have also showed that patients with the PDGFB variant have a tendency for a higher frequency of headaches [20]. The headaches in PBC may be the secondary headaches caused by the dysfunction of the blood-brain-barrier. However, the frequency in more patients and the mechanism of headaches in PBC should be further clarified in the future.

Taken together, support by a multidisciplinary team, including a genetic counsellor, is necessary from an early stage. Judging from the government collected data at the end of 2018, the ages of patients are widespread, from 30s to late-stage elderly, peaking for those in their 60s [21, 22]. Not only genetic support, but also general counseling and employment support, are important for working patients. When we think about support for the patients, it is necessary for us to take into consideration the results of this study that indicate they do not want to participate in the patient association while they are relatively fine. This result reflects their perception that they may not obtain useful information in the meetings because there is no curative medicine. Moreover, this is because of common beliefs about intractable diseases in our contemporary world. The experience of patients with hereditary diseases and their families is very similar to the experience of patients with chronic diseases and their families. One report says that this experience is related to stigma in society [23]. As such stigma reduces self-esteem and self-efficacy and provokes a sense of social isolation. We must start with efforts to make healthcare professionals understand the disease. For example, we need to build a website that gathers information based on patients’ experience and links to a page within the Japan Intractable Diseases Information Center website (https://www.nanbyou.or.jp/entry/3838, in Japanese) [21]. It is necessary for us to promote awareness-raising activities through disseminating accurate information on the disease. If patients can obtain peer support at home through the website, then social isolation, anxiety, confusion, etc. will improve much more [24].

On the other hand, ID5 spent many years seeing CT images of his father, which showed massive calcification. He also saw his father’s forgetfulness and other symptoms. He felt better about talking to his boss about his illness when it became difficult to speak, and because of this, he could work until retirement age. He said that his father’s symptoms were more severe than his and his father had died of aspiration pneumonia. And yet, he was not so pessimistic about the disease. Therefore, patients can avoid unnecessary anxiety through understanding the actual situation of people who live with the illness. It gives patients a great advantage for understanding how to cope. It would be a beneficial factor for patients to predict the future to some extent and be able to accept it. This can help us inform patients with real, true information. Therefore, support with the above-mentioned multidisciplinary collaboration and information dissemination specific to the disease are required in the patient care.