Concomitant Othello syndrome and impulse control disorders in a patient with Parkinson’s disease: A case report

INTRODUCTION

Othello syndrome (OS), also defined as delusional jealousy, is characterized by paranoid delusional beliefs concerning the infidelity of a partner, which may lead to extreme behaviors[1]. This syndrome has been observed in psychiatric patients and neurological patients, such as those with stroke[2], dementia, and Parkinson’s disease(PD)[3]. In a retrospective study of 105 patients with OS at the Mayo Clinic[3], 69.5%had neurological disorders while 30.5% had psychiatric disorders; voxel-based morphometry showed grey matter loss was greater in the patients with neurodegenerative diseases and OS, especially the dorsolateral frontal lobes. Hence, OS is an uncommon but potentially dangerous syndrome in patients with PD.

Given its potential for severe consequences, OS should be identified early,especially in patients undergoing treatment with dopamine agonists.

人才培養(yǎng)的基本要求是育人。大學(xué)人才培養(yǎng)應(yīng)注重以下方面：（1）在科學(xué)層面要具備科學(xué)的方法論和認識論。應(yīng)授之以漁。追求考分的學(xué)習(xí)，培養(yǎng)的是解題能力，而不是解決問題的能力，學(xué)歷不能等同于能力，知識好不好用，只有在具體工作中體現(xiàn)。因此，教者應(yīng)循循善誘，旁征博引，明其理、精其術(shù)，舉一反三，以達明理明道。（2）在文化層面要具備正確的人生觀、價值觀和世界觀。育人不能只看分數(shù)，更應(yīng)看為人之道。追求功利的學(xué)習(xí)，培養(yǎng)的只是狹隘的個人幸福。夫不能報國，不能善待，其擁萬貫不能盡意，其擁相位不能達欲，不可謂君子，不可謂人才，關(guān)鍵在立德樹人。

Impulse control disorders (ICDs) refer to behaviors involving repetitive, excessive,and compulsive activities driven by intense desire[4]. These behaviors include pathological gambling, hypersexuality, compulsive shopping, and binge eating. As ICDs in PD have received increasing attention, the clinical symptom spectrum has gradually expanded to include dopamine dysregulation syndrome, hobbyism, and punding[5]. Both OS and ICDs in PD may be considered as side effects of dopamine agonists[6]. At present, there are only a few case reports and studies related to PD patients with concomitant OS and ICDs. We present the case of a male patient diagnosed with PD who developed OS and ICDs, and report the results of our review of the related literature.

CASE PRESENTATION

Chief complaints

OS in PD is reported infrequently; thus, we conducted a search of the Englishlanguage research literature from 2000-2021 in the MEDLINE database (https://www.ncbi.nlm.nih.gov), using the following keywords: Othello syndrome,delusional jealousy, delusions, jealousy and PD. The search yielded one case report[8],two case series[9,10], and four studies[6,11-13], which we reviewed in addition to our case report. The characteristics of a total of 28 patients who had PD with concomitant OS and ICDs are presented in Table 1.

11月2日，在廣東珠海斗門蓮洲鎮(zhèn)東灣村一塊水稻試驗田邊，2018天禾加鉀平衡施肥項目水稻觀摩會如期而至。雖然臺風(fēng)帶來風(fēng)雨天氣，卻未能阻擋大家參與的熱情。在現(xiàn)場，有農(nóng)民豐收的喜悅、有種植戶關(guān)切的咨詢、有專家科學(xué)的指導(dǎo)，也有天禾加鉀人忙碌的身影。

History of present illness

The patient noticed he had a right-hand tremor ten years ago and then developed akinesia and rigidity. He was diagnosed with PD by a neurologist approximately one year later. Following treatment with levodopa-benserazide (200-50 mg/d), he initially showed significant improvement. His symptoms then progressed to difficulty turning during a walk, constipation, olfactory dysfunction, and vivid anxiety-provoking dreams. Seven years ago, the patient engaged in binge eating with a significant increase in food consumption, eating 3-4 times at night, and the symptoms lasted approximately one year. Six years ago, pramipexole (0.75 mg/d) and selegiline (1 mg/d) were prescribed. His pramipexole dosage was titrated up to 1.5 mg/d. In the past year, his memory has declined, especially his recent memory. About six months ago, he began to accuse his wife of having an affair with someone, although he could not provide any evidence of infidelity. The delusional belief was confirmed by his wife and two children. At the same time, he began to show an obvious increase in libido presenting as frequent masturbation. Three months before his current admission to the hospital, he developed visual hallucinations of seeing ghosts in the window. This visual hallucination was so vivid that he often asked family members to exorcise the ghosts.

History of past illness

The patient was otherwise healthy. He denied a history of hypertension, diabetes mellitus, prior cerebrovascular disease, or other neurological complications. He had no past psychiatric history.

Personal and family history

物資采購的質(zhì)量對企業(yè)產(chǎn)品品質(zhì)起著決定性作用。企業(yè)產(chǎn)品生產(chǎn)過程中，原材料質(zhì)量、生產(chǎn)技術(shù)和管理等因素都對產(chǎn)品最終品質(zhì)產(chǎn)生影響，無疑原材料的質(zhì)量把關(guān)是影響產(chǎn)品品質(zhì)的第一道關(guān)卡。如果采購工作中對物資的質(zhì)量把關(guān)不嚴，則無論生產(chǎn)技術(shù)水平多高、管理能力多強，最終生產(chǎn)出來的產(chǎn)品質(zhì)量都得不到保障，最終會影響企業(yè)的聲譽，并影響企業(yè)的長遠發(fā)展。

Physical examination

The patient’s symptoms showed marked improvement at the follow-up visit two months later, the delusion concerning his wife’s infidelity subsided and his motor syndrome remained stable.

The patient had a college diploma and was retired from the Municipal People's Procuratorate. He denied a past history of drug or alcohol abuse, smoking, and sexual promiscuity. One of his five siblings had PD, but there was no family history of psychiatric illness. The patient is married and has two children who are living independently.

Laboratory examinations

The following laboratory tests were within normal limits: blood cell count, liver and renal function, thyroid function, electrolytes, vitamin B12, folate, syphilis, and tumor markers.

Imaging examinations

Magnetic resonance imaging (MRI) showed mild bilateral frontotemporal atrophy(Figure 1). The T1, T2 and FLAIR sequence showed temporal atrophy, with broadening of the posterior horn of the lateral ventricle (Figure 1A-C); and the magnetic resonance sagittal view showed mild frontal lobe atrophy (Figure 1D).

從業(yè)人員整體素質(zhì)偏低，缺少優(yōu)秀專業(yè)人員，是行業(yè)內(nèi)的一大問題。在如今階段，除了央視廣播電視頻道能夠做到對信息的實時更新和傳播，大多數(shù)地方廣播電視臺受到節(jié)目播出時間、技術(shù)落后等各種因素影響，大部分新聞、資訊播出具有延時性。這樣就非常容易造成在信息反饋給大眾時，發(fā)現(xiàn)新聞播出，但是信息已發(fā)生變化的現(xiàn)象，這就使新聞報道失去了真正的意義。

FINAL DIAGNOSIS

PD with OS, ICDs, and dementia were diagnosed based on the patient’s symptoms and findings from the neurologic examination.

TREATMENT

The patient’s dose of pramipexole was reduced to 50% of the current dosage, and quetiapine 25 mg/d was prescribed. Entacapone was added to alleviate the worsening of his motor symptoms.

OUTCOME AND FOLLOW-UP

The patient’s general examination was unremarkable. The neurologic examination revealed a masked-like facial expression. The motor examination revealed moderate bradykinesia and rigidity of all four limbs. Mild resting tremor was present in the patient’s right upper extremity, and he exhibited difficulty in the initiation of walking and turning. A reduced arm swing was observed when walking, and his performance on the pull-back test was negative. No other positive neurological signs were found.The patient’s scores on the rating scales were as follows: 29 on Part III of the Unified PD Rating Scale, stage II on the Hoehn and Yahr scale, 9/30 on the Mini-Mental State Examination, 13/30 on the Montreal Cognitive Assessment Scale, 11 on the Hamilton Depression Rating Scale, and 11 on the Hamilton Anxiety Rating Scale.

DISCUSSION

Although PD is a common degenerative neurological disorder with typical motor symptoms, its non-motor symptoms have received increasing attention. The most recent update on treatments for non-motor symptoms of PD authored by the Evidence-Based Medicine Committee of the International Parkinson and Movement Disorder Society includes ICDs[7], whereas OS, which has a relatively lower prevalence, is reported less often. In a cross-sectional study of ICDs and OS[6] in 1063 PD patients, 81 of them presented with ICDs (7.61%) and 23 presented with OS(2.16%), while 9 patients presented with both OS and ICDs. A diagnosis of OS is infrequent in PD patients, but its occurrence may have severe consequences. Here, we report the case of a 70-year-old male PD patient with concomitant OS and ICDs, who had a good response to a reduction of his pramipexole dosage and the addition of quetiapine to his medication regimen.

A 70-year-old right-handed man, who showed the first signs of PD at 60 years of age,was admitted to our hospital for behavioral alterations. He presented with a six-month history of a delusional belief that his wife was having an affair with someone. At the same time, he began to show an obvious increase in libido presenting as frequent masturbation.

Concomitant OS and ICDs were more common in males (24 patients) and in middleaged patients. In a retrospective case series study in the Mayo Clinic, 61.9% (65/105) of the patients were male[3]. Similar results were found in studies on PD with ICDs. A prospective multi-center study found that PD patients with ICDs were more likely to develop in males, younger patients, and patients with an earlier onset of PD[14]. The average age of PD onset was 47.00 ± 8.63 years, and only two patients who developed OS were older than 70 years. The mean duration of PD at OS onset was 7.04 ± 3.99 years, which was similar to the previous study at the Mayo Clinic[11].

各個沿海地區(qū)因其所在位置、環(huán)境不同，所屬的沿海景觀也會有所區(qū)別，就好比兩個地域的景觀帶不可能會出現(xiàn)相同景觀。對于景觀設(shè)計來說，地域性不是實物，它既能融入景觀，讓景觀更容易被認知、被理解，又為景觀提供參考價值。特別是當(dāng)沿海景觀帶附近的地形地貌、植被、樹木、水體、光體都被列為地域中的一部分時，景觀設(shè)計就應(yīng)遵循地域性原則，這已被大家列為常識。然而越來越多的海岸景觀已被逐步趨于同化，而忽略了地域文化中的內(nèi)涵，少了設(shè)計中的靈魂。在這次瑯岐島的海岸線規(guī)劃中，因地制宜，恰當(dāng)結(jié)合當(dāng)?shù)氐牡匦物L(fēng)貌、地域文化來展示自己“山、海、島、城”風(fēng)光，設(shè)計出能展現(xiàn)當(dāng)?shù)匚幕坝^節(jié)點，豐富沿海景觀線。

Among the ICDs in our review, hypersexuality (HS) was most prevalent (23/28 patients). Pathological gambling was observed in 9 patients, compulsive shopping in 6 patients, binge eating in 2 patients, punding in 2 patients, and dopamine dysregulation syndrome in 2 patients. HS is characterized by excessive sexual thoughts or behaviors or an atypical change from baseline behavior, such as an inappropriate or excessive sexual desire for the partner, compulsive masturbation, or the development of paraphilias[5]. A functional MRI study compared a group of 12 PD patients with HS with a control group with PD without HS or other ICDs[15]. The results showed an increase in sexual desire in PD patients with HS after exposure to sexual cues; and the increased sexual desire correlated with enhanced activation in the ventral striatum,cingulate cortex, and orbitofrontal cortex. The pathophysiology of OS remains unclear.A previous study showed that OS is associated with the dopaminergic frontostriatal circuits, ventromedial prefrontal cortex, and insula[16]. Overall, both HS and OS were found to be associated with hyperdopaminergic behaviors[13].

Previous studies have shown a relationship between dopamine agonists and OS[9,17-19]. One of these studies, a cross-sectional prevalence study of 805 consecutive PD patients, revealed a significant association between dopamine agonists and OS (odds ratio, 18.1)[17]. Other dopaminergic medications have been reported to have an association with OS, such as amantadine[20], levodopa[9], and selegiline[21]. In our review, all 28 patients were using dopamine agonists at the onset of OS, consistent with the results of previous studies. Pramipexole and ropinirole were used most frequently by 11 patients, pergolide was used by 3 patients, and cabergoline, piribedil,and rotigotine were each used by 1 patient. The duration of treatment with dopamine agonists at the onset of OS varied from a few months to several years under a stable dose. For example, one of the patients[12] developed OS one month after receiving ropinirole treatment, whereas our patient exhibited characteristics of OS more than five years after receiving pramipexole. In early PD, the dopamine depletion is greatest in the ventrolateral tier of the substantia nigra pars compacta, which projects primarily into the dorsal striatum. Thus, the functioning of the dorsolateral frontostriatal circuit(linking the dorsolateral prefrontal cortex and the dorsal striatum), which mediates executive functions, can be restored by dopaminergic medication[22]. However,dopaminergic medication may cause overdosing of the relatively intact orbital frontostriatal circuit (linking the orbitofrontal cortex and the ventral striatum), which mediates reward processing. Dopamine agonists may induce non-physiological tonic dopaminergic stimulation of the orbital frontostriatal circuit, which can lead to an evaluation of the stimulus as a positive reward, thereby inducing an aberrant salient relationship with a loved one[16], and consequently, a greater fear of losing the relationship, resulting in OS. Furthermore, excessive motivation to achieve sexual goals may lead to HS.

The concurrent development of OS and ICDs in our review was more common among patients without dementia and with moderate motor deterioration. Two age peaks in the incidence of PD with OS have been reported: The first peak is in young patients with mild motor impairment and a negligible decline in cognition and the second peak occurs in advanced PD patients with severe motor and cognitive decline[9]. We believe that OS in our patient was associated with both cognitive impairment and the use of dopamine agonists. In addition to having OS and ICDs, 11 of 16 patients in our review had visual hallucinations, and 6 of 11 patients had a psychiatric history;however, the true prevalence could be much higher. The MRI of most of the patients showed normal findings; only one patient’s MRI showed an old infarct of the right basal ganglia, and another patient’s MRI showed mild left frontotemporal atrophy. In our case, the patient showed mild bilateral frontotemporal atrophy, consistent with dementia.

隨著環(huán)境資源友好型社會建設(shè)的開展，建筑施工中的節(jié)能環(huán)保技術(shù)成為目前施工中需要重視的技術(shù)，在施工中，要對施工人員加強環(huán)保節(jié)能教育，不斷完善施工技術(shù)，合理選擇節(jié)能環(huán)保材料與節(jié)能環(huán)保技術(shù)，在確保建筑滿足相關(guān)技術(shù)標準及住戶要求的基礎(chǔ)上，獲得最好的節(jié)能環(huán)保效果。

OS may lead to marital discord and breakdown or have other negative effects. The treatment of OS in patients with PD includes the withdrawal or dosage reduction of dopamine agonists, plus a prescription for atypical antipsychotics at low doses. In 10 of 17 patients in our review, the syndrome was relieved or eliminated with a dosage reduction or withdrawal of the dopamine agonists. Atypical neuroleptics had to be added to 5 patients’ prescriptions: Clozapine for 1 patient and quetiapine for 4 patients. In our case report, it was necessary to use an antipsychotic (quetiapine),which was tolerated quite well. Improvement in our patient’s symptoms was progressive, although slow and gradual. In a case series of 3 young PD patients with OS receiving dopamine agonists, the OS resolved with the withdrawal of the drug and subsequent treatment with bilateral subthalamic nucleus deep brain stimulation (STN DBS)[11]. In another case report, psychotic symptoms in the form of OS appeared after undergoing bilateral STN DBS, and a gradual resolution was achieved by adding a low dosage of quetiapine[23].

CONCLUSION

Both OS and ICDs in PD may be side effects of dopamine agonist therapy. There is a frequent association between OS and ICDs; thus, when the features of either syndrome appear, the features of the other syndrome should be investigated. Clinicians should be aware of OS in patients with PD so they can identify it early, especially in patients treated with dopamine agonists, to help them avoid the devastating psychosocial consequences of this syndrome. PD patients may consider them unrelated to dopamine replacement therapies and even conceal the syndrome to their physician,resulting in challenging and late diagnoses. Patients and their partners should be warned about this uncommon but consequential syndrome. Withdrawal or reduction of dopamine agonists, plus prescriptions of atypical antipsychotics, can usually alleviate symptoms of the syndrome.

基于M/S模式的可定制農(nóng)產(chǎn)品產(chǎn)地環(huán)境數(shù)據(jù)采集系統(tǒng)充分利用了移動互聯(lián)網(wǎng)發(fā)展帶來的成果，通過手機端瀏覽器訪問形式完成數(shù)據(jù)采集工作，具有方便靈活、快捷高效的特點，從而滿足了移動數(shù)據(jù)采集的需要；服務(wù)器端的定制化操作面向不同數(shù)據(jù)采集需求，保證了數(shù)據(jù)的安全性及完整性，滿足多用戶并發(fā)操作。系統(tǒng)整體設(shè)計采用M/S模式，實現(xiàn)了跨平臺操作，并在服務(wù)器端對數(shù)據(jù)操作及邏輯處理實行了封裝化，提高了操作效率，減輕了系統(tǒng)的后期維護工作。使用手機作為移動端采集設(shè)備，具有普遍適用性，降低了采集設(shè)備成本。在建設(shè)國家級農(nóng)產(chǎn)品產(chǎn)地環(huán)境信息庫時，利用此系統(tǒng)完成樣地農(nóng)產(chǎn)品環(huán)境數(shù)據(jù)采集工作，在實際應(yīng)用中，取得了良好的效果。

We are grateful to the patient for giving us his permission to submit this paper for publication.