Patients With Hemangioblastoma: Mood Disorders and Sleep Quality

Abstract

Background

Sleep has confirmed physical, psychological, and behavioral benefits, and disruptions can result in disturbances in these states. Moreover, it can be linked bidirectionally with susceptibility to and the subsequent status of brain tumors. The current study examined mood disorders and sleep quality before and after surgery for hemangioblastoma brain tumors.

Methods

Thirty-two patients diagnosed with hemangioblastoma brain tumors between 2017 and 2023 underwent surgical treatment. The Karnofsky Performance Status and ECOG performance status scales, the Brunel Mood Scale, the Morningness-Eveningness Questionnaire, and the Mini-Sleep Questionnaire were employed to assess the patients.

Results

The findings indicate that after surgery, sleep quality and mood disorders, including tension, vigor, and depression, did not exhibit significant differences in these patients (p>0.05). However, tension, vigor, depression, and sleep quality did have a significant impact on their functional status post-surgery (p<0.05).

Conclusion

Depression is the significant mood factor in patients with brain tumors that impact their functional status. In this context, it is recommended that psychological therapies be considered for them, alongside conducting more comprehensive and in-depth studies on psychological disorders in patients with brain tumors.

INTRODUCTION

Hemangioblastomas, being benign neoplasms, are highly vascular and have slow growth rates [1]. They typically affect the central nervous system and account for approximately 1%–2.5% of all intracranial tumors, about 2%–3% of all intracerebral neoplasms, and 2%–10% of primary spinal cord neoplasms [2]. These highly vascular tumors usually occur in the cerebellum (45%–50%), followed by the spinal cord (40%–45%), and brainstem (5%–10%) [3].

Hemangioblastomas appear as single and scattered lesions in approximately 70%–80% of cases [4]. The remaining cases are related to Von Hippel-Lindau disease, which is an inherited condition with autosomal dominant inheritance, and it predisposes individuals to have multiple hemangioblastomas and other visceral lesions throughout life [5]. These tumors predominantly affect adults, with a peak incidence in the third and fifth decades of life, and they are somewhat more common in males than females [2].

Hemangioblastomas of the central nervous system do not invade or metastasize, but they can cause symptoms due to tumor-related bleeding or compression of adjacent structures [6]. Depending on their anatomical location and growth pattern, they can become significant causes of morbidity and mortality. A wrong or delayed diagnosis can lead to the use of unnecessary treatments, potentially harming the patient, and also result in avoidable complications if appropriate and timely treatment is not provided [7].

The standard treatment for hemangioblastomas includes surgical resection of symptomatic tumors. Gross total resection is considered the definitive cure. In addition to surgery, radiotherapy also plays a role in managing central nervous system hemangioblastomas, especially in cases with residual, recurrent, or inoperable lesions [8].

A comprehensive review study 2015 indicated that brain tumors might solely present with psychiatric symptoms. These symptoms can manifest as mood fluctuations, psychosis, memory issues, personality alterations, anxiety, or loss of appetite [9]. Additionally, these symptoms can be misleading, complicating the clinical diagnosis. Further studies also acknowledge that primary and recurrent brain tumors often coincide with psychiatric and behavioral manifestations, including cognitive changes, personality shifts, perceptual disturbances, disruptions in thought content and processing, anxiety, agitation, and mood variations. The severity of these changes tends to correlate with the rapidity of tumor growth [10,11].

An illuminating case report from Iran recounted the experience of a 26-year-old woman who sought treatment for neurological and psychiatric symptoms and was prescribed sedatives and antipsychotic medications. Despite receiving medical attention, she tragically succumbed six months later [12]. The post-mortem examination revealed the presence of a hemangioblastoma tumor. Central nervous system hemangioblastomas are considered benign neoplasms, and patients are expected to improve clinically after surgical intervention. However, due to limited extensive studies on their psychological aspects, the current research seeks to explore mood disorders and sleep quality in these patients before and after surgical procedures.

MATERIALS AND METHODS

The study included 32 patients (18 men and 14 women) with hemangioblastomas who were treated surgically at the University of Isfahan during the period 2017–2023. Code of ethics was received from the ethics committee of Isfahan University of Medical Sciences (IR.MUI.MED.REC.1399.1081). Informed consent form was received from the patients.

The inclusion criteria were all patients who visited two teaching hospitals in Isfahan (Al-Zahra and Kashani) between 2017 and 2022, were diagnosed with hemangioblastomas by a specialist based on pathological results, and had complete file information or information that could be supplemented through phone calls or in-person visits.

The exclusion criteria were patients with incomplete medical files, those who did not consent to answer questions to complete the information during phone calls, and patients whose pathological test results were unavailable.

One year post-surgery, all patients were assessed for mood and sleep disorders. Initially, 32 patients were enrolled in the study. However, following the follow-up phase, the number was reduced to 22 patients (owing to the death of 7 patients and 3 being unreachable).

Patient data were collected using a checklist. The Karnofsky Performance Status (KPS) [13] and the Eastern Cooperative Oncology Group (ECOG) score [14] were used to assess the patients’ performance status. The KPS scale consisted of 11 items, ranging from 0 (passed away) to 100 (totally normal and active). The ECOG scale also consisted of five items, ranging from 0 (totally normal and active) to 5 (passed away). The ECOG score was classified into two groups based on performance status: favorable (≥1) and unfavorable (<1) (Table 1).

Table 1. Karnofsky and ECOG functional status scale.

ECOG	ECOG	%	Karnofsky
Fully active, able to carry on all pre-disease performance without restriction	0	100	Normal; no complaints; no evidence of disease
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work	1	90	Able to carry on normal activity; minor signs or symptoms of disease
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work	1	80	Normal activity with effort; some signs or symptoms of disease
Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours	2	70	Cares for self. Unable to carry on normal activity or to do active work
Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours	2	60	Requires occasional assistance, but is able to care for most of his needs
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours	3	50	Requires considerable assistance and frequent medical care
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours	3	40	Disabled; requires special care and assistance
Completely disabled; cannot carry out any selfcare; Totally confined to bed or chair	4	30	Severely disabled; hospitalization is indicated although death not imminent
Completely disabled; cannot carry out any selfcare; Totally confined to bed or chair	4	20	Very sick; hospitalization necessary; active supportive treatment necessary
Completely disabled; cannot carry out any selfcare; Totally confined to bed or chair	4	10	Moribund; fatal processes progressing rapidly
Dead	5	0	Dead

ECOG, Eastern Cooperative Oncology Group. Adapted from Yıldız Çeltek et al. Turk J Med Sci 2019;49:894-8 [13] and Azam et al. Case Rep Oncol 2019;12:728-36 [14], under the Creative Commons License.

Three standard questionnaires were used, including the Mini-Sleep Questionnaire (MSQ) [15], Morningness-Eveningness Questionnaire (MEQ) [16], and Brunel Mood Scale (BRUMS) [17].

Mini-Sleep Questionnaire

The MSQ was originally developed for screening excessive daytime somnolence (EDS) [15]. The first version included six items investigating symptoms of EDS (fall asleep during the day; suffer from morning fatigue; snoring; wake up during sleep; headache on awakening; chronic unexplained fatigue) and only one item was related to sleep (sleep restless). Subsequently, three items were added regarding sleep quality (difficulty falling asleep; waking up too early; hypnotic medication use). Respondents used a frequency scale of 1–7 (1, never; 2, very rarely; 3, rarely; 4, sometimes; 5, frequently; 6, very often; 7, always). The total sum score offered an estimation of sleep–wake quality, with higher scores reflecting more sleeping problems: 10–24 points for good sleep–wake quality; 25–27 points for mild sleep–wake difficulties; 28–30 points for moderate sleep–wake difficulties; and >30 points for severe sleep–wake difficulties.

Morningness-Eveningness Questionnaire

The MEQ, developed by Horne and Ostberg, was used to assess the study participants’ preference for activity in the morning or evening (sleep chronotype) [16]. It consists of 19 items and the global score varies from 16 to 86. Individuals with values below 42 were classified as evening type; those with values above, as morning type, and those with values between 42 and 58 were regarded as having the intermediate type. The MEQ has high internal consistency reliability (Cronbach alpha=0.86) and high test-retest reliability (r=0.89).

Brunel Mood Scale

The BRUMS has 24 items arranged into six subscales: anger, confusion, depression, fatigue, tension, and vigor, each with four items [17]. The research participant selects, from a numerical rating scale of 0 to 4 (0=not at all, 1=a bit, 2=moderate, 3=enough; 4=extremely), the option they believe best represents the situation at that time, using questions such as “How do you feel now?,” “How have been feeling in the past week, including today?,” or “How have you been feeling?” The sum of the responses of each subscale results in a score that ranges from 0 to 16. The questionnaire does not generate an overall score, and each scale should be examined individually, although the constructs are related.

The items on each subscale are: 1) anger: annoyed, bitter, angry, and bad-tempered (i.e., items 7, 11, 19, 22); 2) confusion: confused, mixed up, muddled, and uncertain (i.e., items 3, 9, 17, 24); 3) depression: depressed, downhearted, unhappy, and miserable (i.e., items 5, 6, 12, 16); 4) fatigue: worn out, exhausted, sleepy, and tired (i.e., items 4, 8, 10, 21); 5) tension: panicky, anxious, worried, and nervous (i.e., items 1, 13, 14, 18); and 6) vigor: lively, energetic, active, and alert (i.e., items 2, 15, 20, 23).

Statistical analysis

Statistical analyses were performed using SPSS Statistics version 16 (SPSS Inc., Chicago, IL, USA). A p value <0.05 was considered significant. Mean and standard deviation were used to characterize quantitative factors. The distribution and frequency of qualitative factors were reported using descriptive statistics. Statistical methods were used to analyze the data, including the paired-samples t-test and Pearson’s correlation coefficient.

RESULTS

The demographic and clinical characteristics of the patients are shown in Table 2. The age of the patients was 44.28±15.15 years and 18 (56.3%) were male. The follow-up time of the patients was 6.71±3.57 years. Also, the average tumor size was 35.40±12.98 mm. Nine patients (28.1%) underwent radiotherapy in addition to surgery and five patients (15.6%) underwent chemotherapy.

Table 2. Demographic and clinical characteristics of the patients.

Variables	Total (n=32)
Age (yr)	44.28±15.15
Sex, male	18 (56.3)
Duration of the disease (yr)	7.75±4.57
Follow-up (yr)	6.71±3.57
Tumor size (mm)	35.40±12.98
Radiotherapy, yes	9 (28.1)
Chemotherapy, yes	5 (15.6)
Expired patients, yes	7 (21.9)
Duration of death after surgery, year	3.25±1.44

Values are presented as mean±standard deviation or n (%).

In Table 3, the functional status of KPS and ECOG, as well as the mood and sleep quality of patients before and after surgery are shown. As can be seen, KPS, ECOG, and mood disorders (including anger, confusion, and fatigue) showed a significant difference before and after surgery (p<0.05). However, no significant difference was observed in mood (including depression, tension, and vigor) (p>0.05).

Table 3. Functional and mood disorders of patients before and after surgery.

Variable		Before (n=32)	After (n=22)	p value
Functional status (KPS)		47.6±13.57	59.2±19.77	0.001
Functional status (ECOG)		3.45±1.78	2.03±1.19	0.0001
MSQ		31.27±2.94	29.72±1.83	0.342
BRUMS
	Anger	13.14±2.74	9.43±1.76	0.002
	Confusion	11.53±1.46	8.87±2.32	0.0001
	Depression	9.46±1.56	8.42±1.42	0.434
	Fatigue	11.87±1.67	9.48±1.35	0.003
	Tension	11.28±2.12	10.36±2.31	0.328
	Vigor	10.66±1.59	9.84±1.53	0.567
MEQ		-	61.23±17.4	-
	Evening type	-	21 (65.6)	-

Values are presented as mean±standard deviation or n (%). KPS, Karnofsky Performance Status scale; ECOG, Eastern Cooperative Oncology Group scale; MSQ, Mini-Sleep Questionnaire; BRUMS, Brunel Mood Scale; MEQ, Morningness-Eveningness Questionnaire

Twenty-one individuals (65.6% of the patients) exhibited improved daytime activity after surgery compared to other times.

In Table 4, the correlation between the investigated variables after surgery is shown. As can be seen, there was a significant and direct relationship between sleep quality and the two scales of KPS (p=0.0001, r=0.432) and ECOG (p=0.001, r=0.213). There was a significant and direct relationship between depression and sleep quality (p=0.0001, r=0.116) and a significant and inverse relationship with KPS functional status (p=0.001, r=-0.345). A significant and inverse relationship was also observed between vigor and functional status of KPS (p=0.001, r=-0.567).

Table 4. Correlation between the investigated variables.

Variable	KPS	ECOG	Sleep quality	Anger	Confusion	Depression	Fatigue	Tension	Vigor
KPS	1
ECOG	0.986 (0.342)	1
Sleep quality	0.432 (0.0001)	0.213 (0.001)	1
Anger	0.102 (0.321)	0.287 (0.547)	0.143 (0.271)	1
Confusion	0.143 (0.123)	0.117 (0.344)	0.324 (0.456)	0.154 (0.722)	1
Depression	-0.345 (0.001)	0.334 (0.054)	0.116 (0.0001)	0.341 (0.356)	0.098 (0.921)	1
Fatigue	0.189 (0.675)	0.476 (0.216)	0.137 (0.329)	0.287 (0.436)	0.657 (0.335)	0.587 (0.423)	1
Tension	-0.234 (0.001)	0.137 (0.002)	0.519 (0.001)	0.712 (0.001)	0.642 (0.571)	0.337 (0.0001)	0.387 (0.067)	1
Vigor	-0.567 (0.001)	0.657 (0.057)	0.167 (0.645)	0.226 (0.389)	0.567 (0.218)	0.546 (0.546)	0.345 (0.775)	0.565 (0.923)	1

Data are Pearson’s correlation coefficient r (p values). KPS, Karnofsky Performance Status scale; ECOG, Eastern Cooperative Oncology Group scale

There was a significant direct relationship between tension and depression (p=0.0001, r=0.337), sleep quality (p=0.001, r=0.519), ECOG (p=0.002, r=0.137), and anger (p=0.001, r=0.712). However, the relationship between tension and functional status of KPS was significant and inverse (p=0.001, r=-0.234).

DISCUSSION

Patients with brain tumors can experience a range of neurological, cognitive, and psychiatric symptoms that have a significant impact on their daily lives. This review specifically focuses on mood disorders and sleep quality in patients with hemangioblastoma. The findings indicate that after surgery, sleep quality and mood disorders, including tension, vigor, and depression, did not exhibit significant differences in these patients. However, tension, vigor, depression, and sleep quality did have a significant impact on their functional status post-surgery (p<0.05).

According to studies conducted by Giovagnoli [18], Taphoorn and Klein [19], and Mukand et al. [20], nearly 80% of patients with brain tumors experience various neurological or cognitive symptoms during the course of their disease, particularly after undergoing treatment. Additionally, two other studies revealed that besides significant neurological-cognitive disorders, patients with brain tumors are more susceptible to reactive mood disorders, such as depression and/or anxiety, compared to healthy individuals or patients with other cancers not involving the central nervous system. The current study also observed that tension and depression persist in these patients despite successful treatment.

A study conducted in Italy by Leonetti et al. [21] found that factors related to mood disorders and low quality of life in patients with glioma vary throughout the disease. Mood disorders and low quality of life were evident in individuals with low-grade glioma from the third month after surgery.

In California, Tibbs et al. [22] stated that, after studying 54 patients undergoing radiotherapy, increased depression and anxiety were independently associated with worsened neurological cognition, especially in attention/processing speed, among patients with brain tumors. In the present study, although depression and tension decreased after surgery, they did not significantly differ from preoperative levels.

Sharma et al. [23], in India, conducted a study on 176 patients with brain tumors and reported that 27% of them exhibited psychiatric symptoms. Depression was the most common symptom, affecting 24% of the patients, followed by anxiety disorders. Psychiatric symptoms were more prevalent in supratentorial tumors compared to infratentorial tumors. Additionally, it was noted that psychiatric symptoms were more associated with malignant tumors and edema around the tumor. Gliomas had the highest rates of depression, whereas meningiomas had the lowest. Similar to the present study, depression was observed in patients after surgery.

In the study conducted by Pidani et al. [24] in Pakistan, 51 patients with brain tumors were examined. The findings indicated that depression is a common occurrence among individuals with primary brain tumors and directly affects their functional status, which aligns with the results of the current investigation. Furthermore, it was observed that tumor-related and treatment-related factors, such as tumor grade, location, type, and hemisphere involvement, did not show any significant correlation with depression.

In Italy, Ghandour et al. [10] pointed out that brain tumors can present with various psychiatric symptoms, with or without accompanying neurological signs. However, a systematic description of the specific symptoms that warrant neurological evaluation has not been provided yet. Moreover, in adults, the appearance of focal or general neurological symptoms after psychiatric symptoms, rather than concurrently with them, significantly delayed the diagnosis. Therefore, timely evaluation of psychiatric symptoms may contribute to an early diagnosis of brain tumors.

To summarize, it can be concluded that patients with brain tumors often exhibit common behavioral and neurological symptoms, which can have multiple underlying causes. Accordingly, different symptoms may require distinct therapeutic approaches, making it crucial to adopt a comprehensive treatment strategy involving pharmacological and/or psychotherapeutic interventions for these patients.

One notable limitation of the study is the accurate estimation of mood and sleep quality in these individuals, along with assessing the extent of their impact on daily functioning and family life, which demands a more comprehensive approach. Additionally, it is recommended to investigate these quality at different time points to determine the timing of their occurrence and whether they intensify or diminish.

Based on the results, patients with hemangioblastoma showed significant differences in functional and mood disorders (including anger, confusion, and fatigue) before and after surgery. Consistent with other studies, depression was the significant mood factor in patients with brain tumors, affecting their functional status. Therefore, conducting more comprehensive studies on the psychological disorders of patients with any brain tumor and considering psychological therapies as part of the treatment process for these patients is recommended.

Availability of Data and Material

The datasets generated or analyzed during the study are not publicly available due to containing information that could compromise the privacy of research participants but are available from the corresponding author on reasonable request.