Epidemiology and aetiology

In children and adolescents, psychogenic pseudosyncope typically occurs between the ages of 10 and 15, with a higher prevalence in females compared to males. ^{Reference Zhang, Li and Liang6–Reference Heyer, Harvey and Islam10} The reported prevalence of psychogenic pseudosyncope varies significantly in the literature, ranging from 1% to 18.9%. ^{Reference Tannemaat, Thijs and Van Dijk11–Reference Van Campen and Visser14} The prevalence of psychogenic pseudosyncope in children and adolescents is 12.3% in China. ^{Reference Zhang, Li and Liang6} It is evident that psychogenic pseudosyncope is one of the important causes of transient loss of consciousness in children.

Psychogenic pseudosyncope is essentially a form of conversion disorders, characterised by neurological symptoms due to psychological disorders. Conversion disorders is characterised by the presence of one or more symptoms of altered voluntary motor or sensory function, and the symptom or deficit is not better explained by another medical or mental disorder. What is more, the symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation. ¹⁵ In most cases, symptoms are abrupt in onset and initiate from a minor illness or injury. ^{Reference Leary16} The pathogenesis of conversion disorders is currently unclear. Former studies explained that the symptoms of conversion disorders reflected errors in how information about body state was processed and represented, where psychological factors induced brain dysfunction in susceptible individuals. ^{Reference Kozlowska17–Reference Su19} Stone et al. ^{Reference Stone, Zeman and Simonotto20} found that when patients with conversion disorders were asked to move their “weak” limbs during a functional magnetic resonance imaging examination, they demonstrated activation in a network of regions, including the putamen and lingual gyri bilaterally, the left inferior frontal gyrus, the left insula, and concurrent deactivation in the right middle frontal and orbitofrontal cortices. Vuilleumier et al. ^{Reference Vuilleumier, Chicherio and Assal21} reported that single photon emission computerised tomography in patients of conversion disorders with unilateral sensorimotor loss revealed a consistent decrease of regional cerebral blood flow in the thalamus and basal ganglia contralateral to the deficit and resolved after recovery.

As a manifestation of conversion disorders, the aetiology of psychogenic pseudosyncope is related to genetic, psychological, physical, and sociocultural factors: ^{Reference Su19} (1) Genetic factor: There is a genetic basis for conversion disorders in children. Ani et al. ^{Reference Ani, Reading and Lynn22} found that 26% of patients with conversion disorders had family members diagnosed with psychiatric disorders such as depressive and anxiety disorder, and 3% had a family history of conversion disorders. In a study conducted by Spagnolo et al., ^{Reference Spagnolo, Norato and Maurer23} 18 single-nucleotide polymorphisms from 14 candidate genes were examined in 69 patients with conversion disorders. The results indicated that a tryptophan hydroxylase 2 gene polymorphism, G703T, was a significant predictor of both clinical and neurocircuitry manifestations of conversion disorders. Additionally, the tryptophan hydroxylase 2 genotype showed a significant interaction with childhood trauma, suggesting that it may serve as a valuable predictor of symptom severity. Apazoglou et al. ^{Reference Apazoglou, Adouan and Aubry24} found that methylation of the oxytocin receptor gene, which is associated with stress regulation, was increased in patients with conversion disorders. (2) Psychological factors: Most children experience acute onset of symptoms under negative psychological factors. Previous studies revealed evidence of unhappiness at school, domestic stress, unresolved grief, or poor intrafamilial communication and feelings of parental rejection in children with conversion disorders. Maloney et al. ^{Reference Maloney25} reported that 97% of children with conversion disorders experienced symptoms onset related to recent family stress, with 88% of them had family communication problems and 58% suffered from unresolved grief due to events such as death of relatives, parental divorce, or moving. Binzer et al. ^{Reference Binzer and Eisemann26} found that conversion disorders group had a higher frequency of parental rejection and less familial emotion warmth than control group (P<0.05). Individuals may often be in a state of anxiety, fear, and sadness owing to traumatic life events, academic pressure, or family misfortune, etc., which can subsequently manifest as physical disorders. (3) Physical factors: Previous studies have found that physical injuries, or some pathophysiologic disease or physiologic events can trigger the onset of conversion disorders. ^{Reference Carson, Hallett and Stone27} These conditions may dysregulate the fronto-parietal attentional network, which is responsible for sensory processing and integration. This dysregulation could lead to erroneous overemphasis, neglect, or improper integration of sensory experiences. ^{Reference Tayeb28} (4) Sociocultural factors: Patients with conversion disorders frequently come from regions with lower educational and economic levels. Osman et al. ^{Reference Osman, Alsharief and Siddig29} found that 87.5% of patients diagnosed with conversion disorders were from lower socio-economic backgrounds. They also observed that 55% of patients had a low level of education. In addition, cultural factors and societal attitudes in relation to sickness can also influence the disease. ^{Reference Mavroudis, Kazis and Kamal30} Patients with psychogenic pseudosyncope are believed to have symptoms that are neither voluntary nor intentional generated although psychogenic pseudosyncope is caused by psychological factors. ^{Reference Walsh, Baneck and Page5,Reference Goldstein and Mellers31}

Clinical features

Psychogenic pseudosyncope shares certain similarities with vasovagal syncope clinically. ^{Reference Zhang, Li and Liang6,Reference Brignole, Moya and De Lange32} Both are more common in young women and often result in sudden falls due to transient loss of consciousness. They may also present with presyncope symptoms, including dizziness, unclear vision, and nausea, among other things. Some patients with psychogenic pseudosyncope experience episodes triggered by prolonged standing, as well as in stuffy environments, while patients with vasovagal syncope may experience syncope because of emotional stress. However, there are significant differences between psychogenic pseudosyncope and vasovagal syncope in some clinical features. The 2018 European Society of Cardiology Guidelines for the Diagnosis and Management of Syncope proposed specific historical clues for the preliminary diagnosis of psychogenic pseudosyncope: ^{Reference Brignole, Moya and De Lange32} (1) The duration of psychogenic pseudosyncope can vary but a much longer duration aids in the diagnosis: patients may lie immobile on the floor for 15-30 min. (2) The eyes are usually closed during episodes. (3) The frequency of attack is high, with multiple attacks possible within a week or even a single day. (4) There is usually no recognisable trigger beforehand. (5) Injury does not exclude psychogenic pseudosyncope.

Psychogenic pseudosyncope has a long period of apparent transient loss of consciousness. ^{Reference Zhang, Li and Liang6,Reference Villafane, Miller and Glickstein33} Heyer et al. ^{Reference Heyer, Harvey and Islam13} observed 52 patients with psychogenic pseudosyncope and found that 50.0% and 34.6% had syncope duration greater than 2 min and 10 min, respectively. Li et al. ^{Reference Li, Zhang and Liao7} conducted a retrospective study involving 233 children aged 5-17 years (183 children with vasovagal syncope and 50 with psychogenic pseudosyncope) and found that the syncope duration in psychogenic pseudosyncope group was significant longer than control group [20.0 (5.8, 60.0) min vs. 2.0 (1.0, 4.0) min, P<0.05] [median (25th percentile, 75th percentile)]. Zhang et al. ^{Reference Zhang, Jiang and Han8} reported that syncope duration in patients with psychogenic pseudosyncope was longer than patients with vasovagal syncope [50.0 (25.3, 74.8) min vs. 5.5 (2.5, 8.4) min, P<0.05] [median (25th percentile, 75th percentile)]. Walsh et al. ^{Reference Walsh, Baneck and Page5} observed 14 patients with psychogenic pseudosyncope (age 35 ± 14 years, 11 female) and found that the syncope duration of patients ranged from a few seconds to over an hour. Tannemaat et al. ^{Reference Tannemaat, Van Niekerk and Reijntjes34} reported that the median duration of apparent transient loss of consciousness in the psychogenic pseudosyncope group was longer than the vasovagal syncope group [median 44 s (range: 2 s to 13 min 31 s) vs. median 20 s (range 4-55 s), P<0.05].

Psychogenic pseudosyncope has a high frequency of events. ^{Reference Alciati, Shiffer and Dipaola4,Reference Brignole, Moya and De Lange32} Benbadis et al. ^{Reference Benbadis and Chichkova35} prospectively evaluated patients referred to the centre for evaluation of recurrent syncope and found that the frequency of events of psychogenic pseudosyncope patients could reach up to 4 times per day. Walsh et al. ^{Reference Walsh, Baneck and Page5} observed 14 psychogenic pseudosyncope patients (age 35 ± 14 years, 11 female) and found that the patients had an average frequency of syncope of 53 ± 35 episodes per year, with 8 patients experiencing daily episodes. Li et al. ^{Reference Li, Zhang and Liao7} statistically found that psychogenic pseudosyncope had a higher daily frequency of syncope episodes than vasovagal syncope [1 (1, 3) times vs. 1 (1, 1) times, P<0.05] [median (25th percentile, 75th percentile)]. Blad et al. ^{Reference Blad, Lamberts and Van Dijk36} conducted a retrospective study on 1,164 patients (23 patients with mixed vasovagal syncope and psychogenic pseudosyncope) who underwent head-up tilt test and found that the frequency of episodes in vasovagal syncope/psychogenic pseudosyncope group was significantly higher than vasovagal syncope group (median 2 per month vs. median 0.25 per month, P<0.05). Zhang et al. ^{Reference Zhang, Li and Liang6} reported that attack frequency in children with psychogenic pseudosyncope was higher than children with vasovagal syncope (median 6 times vs. median 2 times, P<0.05).

Eye closure and head drop are common during an attack in psychogenic pseudosyncope. ^{Reference Tannemaat, Thijs and Van Dijk11,Reference Brignole, Moya and De Lange32} Tannemaat et al. ^{Reference Tannemaat, Van Niekerk and Reijntjes34} conducted a retrospective study of 800 patients (27 patients with psychogenic pseudosyncope, 69 patients with vasovagal syncope) who underwent head-up tilt test from 2006 to 2012 and found that a sudden head drop as well as eye closure were more common in psychogenic pseudosyncope than in vasovagal syncope during episodes (59% vs. 28%, P<0.05; 97% vs. 7%, P<0.05). Heyer et al. ^{Reference Heyer, Albert and Weber9} prospectively observed 80 patients (40 patients of psychogenic pseudosyncope and 40 patients of psychogenic nonepileptic seizures) age 9-22 years and found that head drop and eye closure occurred more often in psychogenic pseudosyncope than in psychogenic nonepileptic seizures (20% vs. 5%, P<0.05; 60% vs. 12.5%, P<0.05).

Profound sweating can occur with psychogenic pseudosyncope and vasovagal syncope. However, the sweating patterns observed in the two diseases are distinct. Heyer et al. ^{Reference Heyer, Harvey and Islam10} found that during head-up tilt test induced syncope episodes in patients with psychogenic pseudosyncope and neurally mediated syncope, the sweat patterns in patients with psychogenic pseudosyncope matched the patterns associated with symptoms of anxiety and panic which were attributed to an emotional form of sweating, while the sweat patterns in patients with neurally mediated syncope corresponded to hypotension sweating patterns. Additionally, patients with psychogenic pseudosyncope typically do not sustain injuries from syncope episodes. ^{Reference Brignole, Moya and De Lange32} Compared to neurally mediated syncope, patients with psychogenic pseudosyncope may show some unique presyncope symptoms such as change in speech or language, tearfulness or crying, and depressed mood. ^{Reference Heyer37} These clinical features can help to distinguish patients with psychogenic pseudosyncope from those with vasovagal syncope.

Diagnosis and differential diagnosis

After history taking, physical examination, and laboratory tests to exclude other causes of syncope, the patient is referred to a paediatric psychiatry specialist for consultation and follow-up, and if the psychiatrist diagnoses the patient with conversion disorders, then a diagnosis of psychogenic pseudosyncope is confirmed. ^{Reference Zhang, Du and Wang38} A detailed history plays a paramount role in the identification of the cause of syncope. ^{Reference Mohanty, Kumar and Kaku39} Psychogenic pseudosyncope has typically been ranked low in the differential diagnosis of syncope in previous literature, considered an uncommon and exclusionary diagnosis, ^{Reference Kapoor40,Reference Linzer, Yang and Estes41} but it is not. Documenting an attack with a home video camera or with head-up tilt test during which heart rate, blood pressure, and electroencephalogram are normal is considered the gold standard for psychogenic pseudosyncope currently. ^{Reference Brignole, Moya and De Lange32}

Psychogenic pseudosyncope needs to be differentiated from vasovagal syncope. Accurate information about transient loss of consciousness episodes from eyewitness observations can make an important contribution to the differentiation of psychogenic pseudosyncope and vasovagal syncope. ^{Reference Chen, Jamnadas-Khoda and Broadhurst42} Psychogenic pseudosyncope predominantly occurs out of hospital and the information of attacks largely relies on eyewitness accounts; however, it is challenging to diagnose psychogenic pseudosyncope based solely on clinical presentations, due to the limited accuracy of eyewitness observations. ^{Reference Thijs, Wagenaar, Middelkoop, Wieling and van Dijk43} Additionally, the head-up tilt test is used as a diagnostic tool to induce syncope episodes and may cause several complications such as psychological fear, severe cardiac arrhythmias, transient aphasia, and convulsions. ^{Reference Chu, Wu and Wang44–Reference Joo, Koo and Yim47} Furthermore, the head-up tilt test necessitates the involvement of skilled medical personnel to conduct the test and manage any arising complications, posing significant challenges for implementation in primary care hospitals. To solve the problems mentioned above, Zhang et al. ^{Reference Zhang, Jiang and Han8} conducted a retrospective study involving 176 children with syncope (150 cases of vasovagal syncope and 26 cases of psychogenic pseudosyncope) and found that QT dispersion was significantly higher in vasovagal syncope than in psychogenic pseudosyncope [41.3 (38.7, 44.0) ms vs. 27.9 (22.5, 33.3) ms, P<0.05] [median (25th percentile, 75th percentile)], and a DUQ scoring model was established for differentiation between psychogenic pseudosyncope and vasovagal syncope. In the scoring model, three points were given for a duration (D) of syncopal episode>30 min; two points for those without upright (U) posture as an inducement factor; and one point for QT dispersion (Q)<31 ms. When the total points were ≥3, the DUQ model yielded a sensitivity and specificity of 91.3% and 76.9%, respectively, for the diagnosis of psychogenic pseudosyncope. What is more, the negative and positive predictive values of the model were 78.8% and 91.7%, respectively, in the external validation test, with an accuracy of 80.8%. Transcranial Doppler can contribute to differentiate psychogenic pseudosyncope from vasovagal syncope by monitoring cerebral blood flow velocity of right middle cerebral artery during episodes. ^{Reference Raj, Rowe and Fleisch48} In patients with psychogenic pseudosyncope, transcranial Doppler signal was observed to be within normal limits. Conversely, patients with vasovagal syncope showed a narrowing of the transcranial Doppler velocity wave during systole and early diastole and onset of negligible diastolic cerebral flow in their transcranial Doppler. Claffey et al. ^{Reference Claffey, Pérez-Denia and Rivasi49} proposed utilising non-invasive near-infrared spectroscopy, a non-invasive and convenient technology employing specific wavelengths of near-infrared light to penetrate brain tissue to accurately assess the cerebral oxygen saturation, to increase the accuracy of diagnosis of psychogenic pseudosyncope. The aforementioned methods and technologies are non-invasive as well as easy to perform, and they can significantly help in the screening and diagnosis of psychogenic pseudosyncope when using appropriately.

Psychogenic pseudosyncope needs to be differentiated from factitious disorder. Factitious disorder, also known as Münchhausen Syndrome or factitious mental disorder, is a kind of special deceptive behaviour which patients falsify physical or psychological signs or symptoms, or induce injury or disease, in oneself or others without obvious external rewards. ¹⁵ The prevalence of factitious disorder ranges from 0.02% to 3%, and it is more common in females among children and adolescents. ^{Reference Yates and Feldman50,Reference Ehrlich, Pfeiffer and Salbach51} Psychogenic pseudosyncope needs to differentiate from factitious disorder with neurological symptoms. Psychogenic pseudosyncope is classified under conversion disorders, where patients often seek rewards such as care or attention and the diagnosis does not require the judgement that the symptoms are not intentionally produced (i.e., not feigned), whereas factitious disorder is absence of obvious rewards and has intentional falsification of disease in oneself. ¹⁵

Psychogenic pseudosyncope also needs to be differentiated from malingering. The essential feature of malingering is the intentional fabrication of physical or psychological symptoms that are either false or grossly exaggerated, and this behaviour is driven by external incentives, including the desire to avoid military duty or work, obtain financial compensation, evade criminal charges, or acquire drugs. ¹⁵ That is, we should consider malingering rather than psychogenic pseudosyncope when there is definite evidence of feigning by the individual (e.g., loss of function is present during the examination but not at home) for the purpose of external incentives like obtaining money.

Treatment and prognosis

The 2018 European Society of Cardiology Guidelines for the Diagnosis and Management of Syncope proposed that somatic disease specialist who diagnosed psychogenic pseudosyncope should announce the psychological diagnosis to patients and their family as well as providing a thorough explanation of the symptoms actively before treatment, which helps patients accept the diagnosis and believe that events are involuntary, thereby avoiding aggravating psychological burden on the patients. ^{Reference Brignole, Moya and De Lange32} Moreover, the physician should provide regular follow-up to patients with psychogenic pseudosyncope and let them know that they will be taken seriously to improve compliance. ^{Reference Raj, Rowe and Fleisch48} Borisovskaya et al. ^{Reference Borisovskaya, Horibe and Bright52} performed three conscious sedation interviews with a 49-year-old female and encouraged her to maintain good mood and accept strong emotions and found that the patient’s symptoms improved significantly on follow-up, with the frequency of attacks decreased from 7 times per day to 3 times per week. Conscious sedation interview, which involves conducting interviews with individuals under the influence of sedative drugs, was once commonly used for conversion disorder. ^{Reference Fackler, Anfinson and Rand53} The patient is in a twilight state and should avoid falling asleep during the interview. This method attempted to encourage the free expression and release of previously repressed emotion. Saal et al. ^{Reference Saal, Overdijk and Thijs54} found that the attack frequency was significantly lower after communicating with patients with psychogenic pseudosyncope of the diagnosis with near one-third of the patients remaining event-free at the follow-up of 4 years. Heyer et al. ^{Reference Heyer, Pabst and Kaucic12} prospectively observed 84 patients of psychogenic pseudosyncope (age 15.5 ± 2.2 years, 78 female) and found that 38.1% of them had immediate resolution after following communication of the diagnosis with patients and families. This highlights the crucial role of physicians in explaining the condition to patients with psychogenic pseudosyncope and their families, and that timely and accurate communication significantly contributes to better management of psychogenic pseudosyncope.

Psychotherapy is now considered as the treatment of choice for psychogenic pseudosyncope and is positive to the outcomes of patients. ^{Reference Alciati, Shiffer and Dipaola4,Reference Ventura, Maas and Rüppel55,Reference Cuijpers, Van Straten and Andersson56} McFarlane et al. ^{Reference Mcfarlane, Allcott-Watson and Hadji-Michael57} reported that 82% of 22 children with conversion disorders got a significant improvement in symptoms after cognitive behavioural therapy. Balconi et al. ^{Reference Balconi, Angioletti and Crivelli58} proposed that mindfulness-based training with neurofeedback technique could enhance the emotional regulation and stress coping skills of patients with psychogenic pseudosyncope. Psychogenic nonepileptic seizures are a form of conversion disorders, and psychogenic nonepileptic seizures and psychogenic pseudosyncope are both classified as psychogenic transient loss of consciousness. ^{15,Reference Brignole, Moya and De Lange32} There is currently a lack of literature on the treatment outcomes for children with psychogenic pseudosyncope, but the treatment used for psychogenic nonepileptic seizures may provide valuable insights for managing psychogenic pseudosyncope. LaFrance et al. ^{Reference Lafrance, Baird and Barry59} conducted a randomised clinical trial on patients with psychogenic nonepileptic seizures and found that cognitive behavioural therapy significantly lessened the frequency of events compared to treatment as usual (refers to the neurologist sharing the diagnosis with the patient and family, while continuing to follow up with the patient and gradually reducing the dosage of the antiepileptic medication in lone psychogenic nonepileptic seizures) or treatment with sertraline alone. Several non-controlled studies found that psychotherapy for patients with psychogenic nonepileptic seizures could significantly reduce the frequency of seizures and the utilisation of health care. ^{Reference Martlew, Pulman and Marson60}

In clinical practice, patients with conversion disorders exhibit varied responses to antipsychotic drugs and the outcomes may not always be satisfactory. ^{Reference Kroenke61} There are no controlled studies of the effects of antipsychotic drugs on psychogenic pseudosyncope. For children with conversion disorders, medication is more often used to manage comorbidities (e.g. anxiety and depression, etc.), but the prolonged use of these medications may increase suggestibility and potentially lead to a protracted course. ^{Reference Su19}

Children with conversion disorders have a better prognosis than adults. Stone et al. ^{Reference Stone, Sharpe and Rothwell62} conducted a 12-year follow-up study on patients with conversion disorders and found that older age at onset was associated with poorer physical functioning at follow-up, suggesting that the prognosis of conversion disorders was related to the age of onset. Reilly et al. ^{Reference Reilly, Menlove and Fenton63} retrospectively analysed and found that children with psychogenic nonepileptic seizures had a better prognosis compared to adults, with remission rates ranging from 43% to 81% in children, which may be attributed to the shorter duration of symptoms or the higher quality of treatment they receive.

The presence of a psychiatric disorder is associated with an increased risk of recurrence. ^{Reference Kouakam, Lacroix and Klug64} Kapoor et al. ^{Reference Kapoor, Fortunato and Hanusa65} found that syncope was frequently comorbid with major depression and generalised anxiety disorder. Furthermore, the one-year recurrence rate for syncope in patients without a psychiatric diagnosis was 15%, compared to 35% in those with any psychiatric disorders (P<0.05). One study found that the one-year recurrence rate of transient loss of consciousness in patients with a single psychiatric disorder was 26%, while the recurrence rate increased to 50% in patients with greater than two psychiatric disorders. ^{Reference Raj, Rowe and Fleisch48} Caring for the mental health of patients with psychogenic pseudosyncope not only alleviates their symptoms but also improves prognosis and reduces recurrence.

Key points

• The diagnosis and treatment of psychogenic pseudosyncope remains challenging, due to its similarities with vasovagal syncope and insufficient awareness of psychogenic pseudosyncope among clinicians.

• Psychogenic pseudosyncope is more common in females, and the prevalence of psychogenic pseudosyncope varies significantly in the literature, ranging from 1% to 18.9%. The aetiology of psychogenic pseudosyncope is related to genetic, psychological, physical, and sociocultural factors.

• Compared to vasovagal syncope, psychogenic pseudosyncope is characterised by prolonged syncope duration, high frequency of events, eye closure and head drop during episodes, and few injuries.

• Head-up tilt test, video- electroencephalogram, non-invasive near-infrared spectroscopy, transcranial Doppler, and scoring models are useful for the diagnosis and differentiation of psychogenic pseudosyncope.

• Psychotherapy is the treatment of choice for psychogenic pseudosyncope, and the effectiveness of pharmacotherapy for psychogenic pseudosyncope still requires further investigation.