Bilingual Side Effect: A Case of Foreign Language Syndrome Following Chlorpromazine-Induced Neuroleptic Malignant Syndrome

Bilingual Side Effect: A Case of Foreign Language Syndrome Following Chlorpromazine-Induced Neuroleptic Malignant Syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Bilingual Side Effect: A Case of Foreign Language Syndrome Following Chlorpromazine-Induced Neuroleptic Malignant Syndrome Sanja Andric Petrovic, Nadja P Maric This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4919126/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Jan, 2025 Read the published version in Annals of General Psychiatry → Version 1 posted 13 You are reading this latest preprint version Abstract Background Foreign language syndrome is rare neuropsychiatric condition which usually follows routine general anesthesia. To the best of our knowledge, the occurrence of foreign language syndrome has not been previously associated with neuroleptic malignant syndrome (NMS) in the existing literature. By documenting the following case, we aim to expand the understanding of NMS's clinical spectrum and highlight the importance of recognizing atypical presentations for prompt diagnosis and effective management. Case presentation: A 34-year-old Caucasian male with a history of schizoaffective disorder and multiple psychiatric hospitalizations was admitted for a depressive episode. His condition deteriorated several hours after intramuscular chlorpromazine administration, leading to NMS, characterized by agitation, muscle rigidity, hyperthermia, autonomic instability, typical characteristic laboratory findings, and altered mental status, including foreign language syndrome. Treatment involved discontinuation of prior psychopharmacotherapy, intravenous hydration and medication (biperiden, and lorazepam). The patient showed significant improvement with resolution of NMS symptoms and normalized sleep patterns upon discharge. Conclusion Foreign Language Syndrome is a rare phenomenon documented in only nine cases to date, all involving male patients. This report introduces a novel case where Foreign Language Syndrome is associated with NMS in a male patient. This case represents the first documented instance of Foreign Language Syndrome linked to NMS in a male, thereby contributing to the understanding of potential sex-specific mechanisms underlying this condition. Neuroleptic malignant syndrome Foreign language syndrome Antipsychotic-induced complications Chlorpromazine Atypical neurological presentations Sex-difference Background Neuroleptic malignant syndrome (NMS) is a rare, life-threatening idiosyncratic reaction typically associated with the recent initiation or dosage increase of medications affecting central dopaminergic neurotransmission. Although NMS is usually associated with high-potency first-generation antipsychotics, it can also be triggered by low-potency first generation antipsychotics and second generation antipsychotics (including clozapine), low-potency, as well as other drugs that antagonize dopamine D2 receptors such as certain antidepressants, mood stabilizers, and antiemetics [ 1 – 3 ]. According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), NMS is classified as a subtype of drug-induced movement disorders [ 4 ]. While traditionally characterized by the triad of fever, muscle rigidity, and altered mental status, NMS can present with a broad spectrum of clinical features (DSM-5 diagnostic criteria are shown in Table 1 ). Table 1 DSM-5 diagnostic criteria for neuroleptic malignant syndrome Major symptoms 1. Rigidity 2. Hyperthermia 3. Diaphoresis 4. Exposure to dopamine antagonists within 72h prior to the beginning of the symptoms Minor symptoms 1. Autonomic nervous system instability Tachycardia (rate > 25% above baseline), hypertonia (> 25% above baseline or with fluctuation), sialorrhea, urinary incontinence, pallor, tachypnea (> 50% above baseline), dyspnea 2. Altered mental status Changes in consciousness, whether qualitative (delirium) or quantitative (ranging from stupor to coma) 3. Motor symptoms Tremor, akinesia, dystonia, myoclonia, trismus, dysarthria, dysphagia 4. Laboratory findings ↑Leukocytes, ↑ Creatine phosphokinase (CPK), ↑Myoglobin, ↑Catecholamines, ↑Creatinine, ↓Fe, Metabolic acidosis, Hypoxia Exclusion criteria The aforementioned symptoms are not attributable to another substance, neurological disorder, or any other general medical condition - Insert Table 1 here - Foreign language syndrome is characterized by patients unexpectedly switching from their native language to a second language and maintaining this switch for certain duration [ 5 ]. This rare phenomenon has been documented in only a few cases within the current literature, typically occurring in the immediate postoperative period [ 5 – 11 ]. Ward and Marshall (1999) [ 6 ] first described a unique case of temporary fixation on a non-native language following routine general anesthesia. A 54-year-old patient, whose first language was English, awoke in the recovery room speaking only Spanish, though he understood English. Before being transferred to the hospital ward, he reverted to speaking English without any issues. The patient later informed his anesthetist that he had learned Spanish in school 40 years earlier but claimed he no longer spoke it. In the years that followed, only a few more cases of foreign language syndrome have been described in the literature [ 5 ], with all cases experiencing spontaneous recovery after a short period. The underlying cause of this language transition remains unclear. Foreign language syndrome should be distinguished from foreign accent syndrome, a rare speech disorder characterized by altered speech rhythm, which has been far more extensively documented in the literature [ 12 ]. To the best of our knowledge, the occurrence of foreign language syndrome has not been previously associated with NMS in the existing literature. In this paper, we report a case of foreign language syndrome associated with chlorpromazine-induced NMS. Case presentation A 34-year-old Caucasian male was admitted to the Department for Psychotic Disorders at the Institute of Mental Health in Belgrade, Serbia, presenting with a depressive episode associated with schizoaffective disorder. His first psychiatric symptoms emerged at the age of 14, manifesting as obsessive thoughts, compulsions, and aggressive behavior towards family, peers, and school property. Initial psychiatric treatment at the Clinic for Child and Adolescent Psychiatry led to a diagnosis of schizoaffective disorder, with subsequent initiation of lithium and clozapine therapy. Throughout adolescence, the patient experienced three psychiatric hospitalizations at the aforementioned clinic due to self-initiated discontinuation of prescribed medication resulting in recurrent decompensations. The fourth hospitalization, at age of 22 (the first in adulthood), followed aggressive behavior towards family members and lead to the introduction of olanzapine 5mg, valproate 500mg, and diazepam 30mg into his treatment. Despite a stable period over the next five years, a gradual tapering of psychopharmacotherapy led to a decline characterized by recurrent aggressive outbursts, resulting in three additional hospitalizations at the local psychiatry department in the place of residence between ages of 28 and 33. The patient’s psychiatric treatment at the Institute of Mental Health in Belgrade began in May 2024, at the age of 34 years. Upon admission, a significant portion of the psychiatric medical records pertaining to previous treatments were unavailable due to patient’s destruction of these documents during a prior exacerbation. Consequently, the available information about past psychiatric treatments and prescribed psychotropic medications was derived from the remaining medical records. According to collateral information, the last prescribed therapy before admission to IMH consisted of levomepromazine 100mg and valproate 1500mg daily. Upon admission, the patient reported experiencing marked apathy, low energy, and significantly diminished motivation over the past six months. He struggled with daily tasks, neglecting his agricultural responsibilities and familial duties. Additionally, he reported tearfulness and persistent insomnia. He denied any history of head injuries, loss of consciousness, or serious somatic illnesses, although he acknowledged occasional alcohol consumption over the past fifteen years, sometimes to the point of intoxication. The information provided about the amount and frequency of alcohol consumption should be interpreted with caution, due to the patient's tendency to minimize their intake. There was no history of use of other substances. Family history revealed a familial burden of psychiatric illnesses, including a brother with intellectual disabilities requiring special education, and a paternal grandfather who died by suicide. On initial assessment, the patient appeared well-groomed, slightly older than his stated age. He was cooperative but demonstrated slight psychomotor retardation with decreased spontaneous movements and reduced facial expressions. He established and maintained eye contact and verbal communication, answered questions in a direct and logical fashion, although with prolonged reaction time. His speech was slow, with a monotonous tone and reduced spontaneity. His mood was moderately to severely depressed, his affect was congruent with thought content, with no visible intensive fluctuations. Anxiety was evident through restlessness and fine hand tremor. Thought processes were logical and coherent but slowed. The content of thought was dominated by Beck's cognitive triad, with nihilistic ideation but denied suicidal or self-harm thoughts. There were no delusions, hallucinations, or obsessive-compulsive symptoms. The patient was alert and well oriented to self, person, place and time. Concentration was impaired as evidenced by difficulties with simple calculations. Immediate and recent memory was mildly impaired. Intelligence was estimated to be in the low-average range with difficulties in abstract thinking. Insight into the illness was fair, with recognition of the need for treatment. Judgment was intact regarding personal care but impaired in terms of complex decision-making. On physical examination, the patient appeared well-nourished and hydrated. Vital signs were within normal limits. A congenital right eyelid ptosis was noted. No evidence of neurological deficits was found. Blood analyses upon admission revealed minor, clinically insignificant variances in creatinine levels (58 µmol/L, reference range: 62 to 106 µmol/L), uric acid (524 µmol/L, reference range: 143 to 416 µmol/L), and sedimentation rate (14 mm/h, reference range: 2 to 12 mm/h), while all other parameters fell within normal limits. Upon admission, therapy adjustment commenced, involving a gradual reduction in the daily dosage of valproate and the introduction of lithium. Persistent insomnia prompted the medical team to administer additional peroral therapy for several consecutive nights, consisting of 15 mg of midazolam, followed by 10 mg of zolpidem, 50 mg of quetiapine, and 10 mg of diazepam. Nevertheless, the patient experienced less than two hours of continuous sleep. Following the intramuscular administration of 50 mg of chlorpromazine in the evening therapy for persistent and refractory insomnia fourth day upon admission, the patient exhibited agitation, failed to establish verbal communication despite being awake, displayed disorganized behavior, and presented with pale, diaphoretic skin in the morning. Vital signs recorded included a body temperature of 37.7°C, blood pressure of 150/90 mmHg, and blood glucose level of 8.4 mmol/L. Rigidity and hypertonicity were observed in the arm and neck muscle groups bilaterally. During the physical examination, the previously non-verbal patient suddenly began conversing fluently in English (which he had learned during childhood but had never spoken outside of school), primarily inquiring about the hospital’s location and the reason for his presence. This episode lasted approximately 5 minutes, after which the patient reverted to non-communication with the medical staff. Due to suspicion of developing NMS, all previous psychopharmacotherapy was discontinued. The following treatments were administered: 500 ml of 0.9% NaCl solution with vitamin B and C intravenously, 5 mg of biperiden hydrochloride intramuscularly, and 2.5 mg of lorazepam orally three times a day. A blood sample was sent for urgent laboratory analysis, which confirmed the suspicion of NMS showing elevated creatine phosphokinase (CPK) values at 1662 IU/L (reference range: 20 to 200 IU/L) and leukocytosis at 9.5x10^9/L (reference range: 4.0 to 9.0 x10^9/L). Additionally, there were several other clinically less significant deviations: sodium 133.0 mmol/L (reference range: 136.0 to 145.0 mmol/L), chlorides 96.0 mmol/L (reference range: 98.0 to 107.0 mmol/L), uric acid 435 µmol/L (reference range: 143 to 416 µmol/L), AST 84 IU/L (reference range: <40 IU/L), CRP 10.52 mg/L (reference range: <5 mg/L), and direct bilirubin 5.7 µmol/L (reference range: <5 µmol/L). Several hours after the administration of the parenteral therapy the patient felt better. On the same day, he was thoroughly examined by an internist. Subjectively, he complained of difficulty speaking, slowness, and instability while walking. Objectively, he was eupneic, obese, subfebrile (body temperature 37.5°C), and his extremities were without swelling. Lung auscultation revealed normal breath sounds, and heart auscultation revealed clear tones without murmurs. His blood pressure was 125/80 mmHg. An ECG showed sinus rhythm with a heart rate of 100 beats per minute, and the ST and T waves were unremarkable. The therapy was adjusted to include bisoprolol 2.5 mg in the morning and amoxicillin/clavulanic acid (875 mg/125 mg) twice daily, along with the parenteral administration of one liter of infusion solution daily (0.9% NaCl with vitamins C and B). After two days, repeat blood biochemical analyses showed a slight decrease in CPK levels (1416 IU/L). For a detailed comparative presentation of the blood laboratory analysis results, see Table 2 . Table 2 Comparative presentation of blood analysis results Laboratory analysis (reference range) Upon admission – day 0 Suspicion of NMS – day 5 Follow-up - day 7 Follow-up - day 11 Follow-up - day 12 Sodium (136.0-145.0 mmol/l) 144.0 133.0 138.0 136.0 140.0 Chlorides (98.0-107.0 mmol/L) 104.7 96.0 102.1 101.9 104.1 Creatinine (62–106 umol/l) 58 70 57 53 56 Urea (1.7–8.3 mmol/l) 2.8 4.0 3.5 3.5 3.9 Uric acid (143–416 µmol/L) 524 435 468 403 373 AST (< 40 IU/L) 19 84 111 39 32 ALT (< 41 IU/L) 15 36 50 46 41 Direct bilirubin (< 5 µmol/L / 5.7 / 2.3 1.4 Albumins (30–50 g/L) / 51 / 48 48 CPK (20–200 IU/L) / 1662 1416 344 212 Total leukocyte count (4.0–9.0 x10^9/L) 5.9 9.5 / 7.4 7.8 Platelets (150–350 x10^9/L) 243 295 / 360 358 CRP (< 5 mg/L) / 10.52 / 1.47 1.14 Sedimentation (2–12 mm/h) 14 4 / / 4 Note: Only the laboratory analysis results that deviated from the reference values at any point during the monitoring are shown; “/” – the analysis was not performed at the given time point. - Insert Table 2 here - Over the following days, two additional internal medicine check-ups were conducted with repeated blood laboratory analyses (refer to Table 2 for details). Parenteral and oral rehydration therapy continued, accompanied by ongoing monitoring of vital signs. The patient remained afebrile, with pulse and blood pressure consistently within normal ranges. Consequently, antibiotics were discontinued after one week, along with bisoprolol. The patient was also examined by a neurologist and an EEG recording was performed. Besides the congenital anomaly of the left eyeball the neurological exam was unremarkable. EEG showed low amplitude basic activity and drug-induced acceleration, without pathological changes. A brain MRI was indicated to be performed after discharge from hospital treatment. Upon stabilization, a psychological assessment was also conducted, indicating low-average intellectual functioning (total IQ 79, verbal IQ 78, performance IQ 77). The personality inventory showed self-defeating and depressive personality dimensions, high level of internal anxiety, and persistent vulnerability to disorganization in response to daily life stressors. Concurrently, the patient's mental state gradually improved, with persistent insomnia and evening irritability as the sole remaining symptoms. Following stabilization of the laboratory parameters, quetiapine was gradually initiated in the evening (dose gradually increased to 200 mg), followed by reduction in the daily lorazepam dose. This resulted in normalized sleep patterns and initial remission upon discharge. Discussion and conclusions NMS, initially termed “fatal hyperpyrexia” in 1956 shortly after the introduction of chlorpromazine [ 13 ] ( AYD, 1956 ), is a rare condition affecting approximately up to 3% of patients using antipsychotic drugs [ 14 , 15 ]. First-generation antipsychotics pose a higher risk compared to newer agents due to their affinity towards D2 receptors. Other established risk factors include dehydration, malnutrition, parenteral administration of antipsychotics, preexisting brain lesions, substance use disorders, and a history of NMS. Treatment involves immediate discontinuation of the offending agent with supportive care, and specific pharmacological interventions (i.e. dantrolene, bromocriptine) recommended for severe cases [ 16 ]. Re-initiating antipsychotic therapy should be approached cautiously, starting with low-potency agents at low doses after at least two weeks of NMS resolution, gradually titrating to achieve therapeutic effect. The pathophysiology of NMS is complex and not fully understood. Most symptoms arise from a sudden reduction in central dopaminergic activity, either from D2 receptor blockade or abrupt withdrawal of D2 receptor stimulation. Mortality rates can reach up to 10%, primarily due to autonomic nervous system instability and complications such as rhabdomyolysis, disseminated intravascular coagulation, acute respiratory or kidney failure, sepsis, and other systemic issues [ 17 ]. Prompt recognition is crucial to prevent adverse outcomes. NMS should be suspected when a cluster of symptoms related to autonomic instability, neuromuscular abnormalities, and central nervous system dysfunction gradually appears in patients treated with medications affecting central dopaminergic neurotransmission. However, atypical presentations can occur. To our best knowledge, nine documented cases of foreign language syndrome exist in the literature to date [ 5 ]. Common features observed in all cases, including ours, include male gender, Caucasian ethnicity, switching from a native language to a second language acquired later in life (rather than being bilingual from the outset), and limited proficiency in the acquired language. The observation that all reported postoperative foreign language syndrome involved males, as well as our NMS-associated case, may be coincidental. However, another plausible explanation related to sex differences in the brain could also be considered. Namely, language lateralization tends to be more pronounced in males, with women often showing bilateral activation during speech while men typically exhibit left hemisphere dominance [ 18 , 19 ]. Half of the cases, including ours, did not recall speaking the foreign language during the episode. A notable feature in most cases is the lack of self-awareness exhibited by patients during transient fixation episodes. Some deny being able to speak their non-native language at all, and most, including our case, are surprised to learn they had spoken it during the episode. Previous reports also document two cases of recurrence: one postoperatively after awakening from anesthesia, and another during severe alcohol intoxication. Both alcohol and anesthetics impact cerebral blood flow and glucose metabolism, with anesthetics having a more suppressive effect. Hypoglycemia has been proposed as a possible contributing factor [ 6 ]. Evidence also suggests that global transient cognitive deficits may be worsened with hypoglycemia. Foreign language syndrome, an exceptionally rare manifestation observed in NMS and other brain conditions, challenges our understanding of language processing in the brain. The precise pathophysiology of this intriguing phenomenon remains uncertain, particularly whether it represents a distinct syndrome on its own or a phenotype of another syndrome such as delirium. Salamah et al. (2022) [ 5 ] proposed that foreign language syndrome might represent a delirium phenotype, rather than a distinct entity. This hypothesis is supported by findings of impaired language functions in delirious patients compared to cognitively unimpaired individuals, including spontaneous speech production, word quantity, speech content, and language comprehension [ 20 ]. Considering these hypotheses and our case presentation, it is reasonable to assume that delirium could be a common underlying factor in the manifestation of foreign language syndrome in our patient with NMS and in postoperative cases documented in previous literature. Language remains one of humanity's most impressive cognitive abilities, yet the mechanisms underlying its processing in the brain remain largely unknown. The anatomical areas responsible for native and foreign languages are not fully understood. The neuropsychological rationale for the substitution of a native language with a later-acquired one suggests that the native language is partly acquired and stored through implicit memory systems in subcortical regions such as the basal ganglia and cerebellum. In contrast, second languages learned through explicit rules are thought to be represented broadly across the cerebral cortex [ 21 ]. Functional brain imaging studies provide evidence of distinct cortical areas associated with native and later-acquired languages [ 22 , 23 ]. Studies also indicate that these areas may overlap in early bilinguals (i.e. who learned a second language before the age of 5), whereas late bilinguals exhibit distinct regions for each language [ 24 ]. Previous theories about the causes of transient fixation on a non-native language under general anesthesia suggest that the separation between native and non-native languages allows differential effects of anesthesia on the brain, with one language faculty remaining active while the other is suppressed [ 6 , 9 ]. Possible mechanisms include suppression of brain areas responsible for native language abilities, whether due to anesthesia or another underlying pathophysiological mechanism, leading to a language switch and compensation from activation of second language centers in different brain regions [ 10 ]. This case report should be considered in light of its limitations. The findings are based on a single patient, limiting their generalizability to a broader population and potentially not reflecting the experiences of other individuals with NMS or foreign language syndrome. Key details about previous treatments and psychiatric history were unavailable due to the destruction of medical records, which may impact the accuracy of the reported associations and the interpretation of the patient's condition. Additionally, the patient’s use of multiple medications and complex psychiatric history introduce confounding factors, complicating the attribution of symptoms solely to NMS or foreign language syndrome. Further research involving additional cases is essential to validate and expand upon these findings. This case points to opportunities for further research into the neurobiological mechanisms linking NMS with foreign language syndrome, sex-differences in the brain and the role of conditions like delirium in language processing. Abbreviations CPK Creatine phosphokinase DSM 5-Diagnostic and Statistical Manual of Mental Disorders NMS Neuroleptic malignant syndrome Declarations Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki, and the conduct of this study was approved by the ethics committee of the Institute of Mental Health in Belgrade, Serbia Consent for publication: Consent for publication was obtained from patient presented in the case-report. Availability of data and materials: All data generated or analysed during this study are included in this published article Competing interests: The authors declare that they have no competing interests Funding: Nothing to declare Authors' contributions : SAP and NM equally contributed to the analysis and interpretation of the patient data, as well as the literature search. Both authors also played an equal role in writing the manuscript. 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Cite Share Download PDF Status: Published Journal Publication published 02 Jan, 2025 Read the published version in Annals of General Psychiatry → Version 1 posted Editorial decision: Revision requested 05 Dec, 2024 Reviews received at journal 23 Nov, 2024 Reviews received at journal 10 Nov, 2024 Reviewers agreed at journal 07 Nov, 2024 Reviews received at journal 05 Nov, 2024 Reviewers agreed at journal 05 Nov, 2024 Reviewers agreed at journal 04 Nov, 2024 Reviewers agreed at journal 03 Nov, 2024 Reviewers agreed at journal 02 Nov, 2024 Reviewers invited by journal 02 Nov, 2024 Editor assigned by journal 15 Aug, 2024 Submission checks completed at journal 15 Aug, 2024 First submitted to journal 15 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4919126","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":344219224,"identity":"ffb76d41-dc2b-4f8d-8139-f562d59e8ca7","order_by":0,"name":"Sanja Andric Petrovic","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYJACAwYGZgY2BuYDQLaEDCla2BJAWniItYgZiHkMQCzCWuTbzx4o+LnDOp+P/cznVzdqLHgY2A8f3YDXUWfyEgx7z6RbtvHkbrPOOQZ0GE9a2g38/sgxMOBtO2zAJsG7zTiHDahFgscMrxb5/jcGhn/BWnieGef8I0ILw40cA2OILTzMj3PbiNBicOONgbFsW7oBG0+aGXNunwQPGyG/yPfnmBm+bbM2kG8//Phzzrc6OX72w8fwO4yBgc0AxpAAkwSUgwDzAxjjAxGqR8EoGAWjYAQCAMrSP27uUOW9AAAAAElFTkSuQmCC","orcid":"","institution":"Faculty of Medicine, University of Belgrade","correspondingAuthor":true,"prefix":"","firstName":"Sanja","middleName":"Andric","lastName":"Petrovic","suffix":""},{"id":344219225,"identity":"5966fc8a-7158-4d75-98ad-42825b896d78","order_by":1,"name":"Nadja P Maric","email":"","orcid":"","institution":"Faculty of Medicine, University of Belgrade","correspondingAuthor":false,"prefix":"","firstName":"Nadja","middleName":"P","lastName":"Maric","suffix":""}],"badges":[],"createdAt":"2024-08-15 11:54:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4919126/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4919126/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12991-024-00538-6","type":"published","date":"2025-01-02T15:57:12+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":73093206,"identity":"4b18db6b-64f6-4fbf-b2af-f41e5f606933","added_by":"auto","created_at":"2025-01-06 16:10:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":515805,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4919126/v1/c006c0e0-3a29-4463-abb8-1f7006669397.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Bilingual Side Effect: A Case of Foreign Language Syndrome Following Chlorpromazine-Induced Neuroleptic Malignant Syndrome","fulltext":[{"header":"Background","content":"\u003cp\u003eNeuroleptic malignant syndrome (NMS) is a rare, life-threatening idiosyncratic reaction typically associated with the recent initiation or dosage increase of medications affecting central dopaminergic neurotransmission. Although NMS is usually associated with high-potency first-generation antipsychotics, it can also be triggered by low-potency first generation antipsychotics and second generation antipsychotics (including clozapine), low-potency, as well as other drugs that antagonize dopamine D2 receptors such as certain antidepressants, mood stabilizers, and antiemetics [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), NMS is classified as a subtype of drug-induced movement disorders [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. While traditionally characterized by the triad of fever, muscle rigidity, and altered mental status, NMS can present with a broad spectrum of clinical features (DSM-5 diagnostic criteria are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDSM-5 diagnostic criteria for neuroleptic malignant syndrome\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eMajor symptoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1. Rigidity\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2. Hyperthermia\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3. Diaphoresis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4. Exposure to dopamine antagonists within 72h prior to the beginning of the symptoms\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eMinor symptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1. Autonomic nervous system instability\u003c/p\u003e \u003cp\u003eTachycardia (rate\u0026thinsp;\u0026gt;\u0026thinsp;25% above baseline), hypertonia (\u0026gt;\u0026thinsp;25%\u003c/p\u003e \u003cp\u003eabove baseline or with fluctuation), sialorrhea, urinary incontinence, pallor, tachypnea (\u0026gt;\u0026thinsp;50% above baseline), dyspnea\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2. Altered mental status\u003c/p\u003e \u003cp\u003eChanges in consciousness, whether qualitative (delirium) or quantitative (ranging from stupor to coma)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3. Motor symptoms\u003c/p\u003e \u003cp\u003eTremor, akinesia, dystonia, myoclonia, trismus, dysarthria, dysphagia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4. Laboratory findings\u003c/p\u003e \u003cp\u003e\u0026uarr;Leukocytes, \u0026uarr; Creatine phosphokinase (CPK), \u0026uarr;Myoglobin,\u003c/p\u003e \u003cp\u003e\u0026uarr;Catecholamines, \u0026uarr;Creatinine, \u0026darr;Fe, Metabolic acidosis, Hypoxia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExclusion criteria\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe aforementioned symptoms are not attributable to another substance, neurological disorder, or any other general medical condition\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e- Insert Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e here -\u003c/p\u003e \u003cp\u003eForeign language syndrome is characterized by patients unexpectedly switching from their native language to a second language and maintaining this switch for certain duration [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This rare phenomenon has been documented in only a few cases within the current literature, typically occurring in the immediate postoperative period [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Ward and Marshall (1999) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] first described a unique case of temporary fixation on a non-native language following routine general anesthesia. A 54-year-old patient, whose first language was English, awoke in the recovery room speaking only Spanish, though he understood English. Before being transferred to the hospital ward, he reverted to speaking English without any issues. The patient later informed his anesthetist that he had learned Spanish in school 40 years earlier but claimed he no longer spoke it. In the years that followed, only a few more cases of foreign language syndrome have been described in the literature [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], with all cases experiencing spontaneous recovery after a short period. The underlying cause of this language transition remains unclear. Foreign language syndrome should be distinguished from foreign accent syndrome, a rare speech disorder characterized by altered speech rhythm, which has been far more extensively documented in the literature [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo the best of our knowledge, the occurrence of foreign language syndrome has not been previously associated with NMS in the existing literature. In this paper, we report a case of foreign language syndrome associated with chlorpromazine-induced NMS.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 34-year-old Caucasian male was admitted to the Department for Psychotic Disorders at the Institute of Mental Health in Belgrade, Serbia, presenting with a depressive episode associated with schizoaffective disorder.\u003c/p\u003e \u003cp\u003eHis first psychiatric symptoms emerged at the age of 14, manifesting as obsessive thoughts, compulsions, and aggressive behavior towards family, peers, and school property. Initial psychiatric treatment at the Clinic for Child and Adolescent Psychiatry led to a diagnosis of schizoaffective disorder, with subsequent initiation of lithium and clozapine therapy. Throughout adolescence, the patient experienced three psychiatric hospitalizations at the aforementioned clinic due to self-initiated discontinuation of prescribed medication resulting in recurrent decompensations. The fourth hospitalization, at age of 22 (the first in adulthood), followed aggressive behavior towards family members and lead to the introduction of olanzapine 5mg, valproate 500mg, and diazepam 30mg into his treatment. Despite a stable period over the next five years, a gradual tapering of psychopharmacotherapy led to a decline characterized by recurrent aggressive outbursts, resulting in three additional hospitalizations at the local psychiatry department in the place of residence between ages of 28 and 33.\u003c/p\u003e \u003cp\u003eThe patient\u0026rsquo;s psychiatric treatment at the Institute of Mental Health in Belgrade began in May 2024, at the age of 34 years. Upon admission, a significant portion of the psychiatric medical records pertaining to previous treatments were unavailable due to patient\u0026rsquo;s destruction of these documents during a prior exacerbation. Consequently, the available information about past psychiatric treatments and prescribed psychotropic medications was derived from the remaining medical records. According to collateral information, the last prescribed therapy before admission to IMH consisted of levomepromazine 100mg and valproate 1500mg daily.\u003c/p\u003e \u003cp\u003eUpon admission, the patient reported experiencing marked apathy, low energy, and significantly diminished motivation over the past six months. He struggled with daily tasks, neglecting his agricultural responsibilities and familial duties. Additionally, he reported tearfulness and persistent insomnia. He denied any history of head injuries, loss of consciousness, or serious somatic illnesses, although he acknowledged occasional alcohol consumption over the past fifteen years, sometimes to the point of intoxication. The information provided about the amount and frequency of alcohol consumption should be interpreted with caution, due to the patient's tendency to minimize their intake. There was no history of use of other substances. Family history revealed a familial burden of psychiatric illnesses, including a brother with intellectual disabilities requiring special education, and a paternal grandfather who died by suicide.\u003c/p\u003e \u003cp\u003eOn initial assessment, the patient appeared well-groomed, slightly older than his stated age. He was cooperative but demonstrated slight psychomotor retardation with decreased spontaneous movements and reduced facial expressions. He established and maintained eye contact and verbal communication, answered questions in a direct and logical fashion, although with prolonged reaction time. His speech was slow, with a monotonous tone and reduced spontaneity. His mood was moderately to severely depressed, his affect was congruent with thought content, with no visible intensive fluctuations. Anxiety was evident through restlessness and fine hand tremor. Thought processes were logical and coherent but slowed. The content of thought was dominated by Beck's cognitive triad, with nihilistic ideation but denied suicidal or self-harm thoughts. There were no delusions, hallucinations, or obsessive-compulsive symptoms. The patient was alert and well oriented to self, person, place and time. Concentration was impaired as evidenced by difficulties with simple calculations. Immediate and recent memory was mildly impaired. Intelligence was estimated to be in the low-average range with difficulties in abstract thinking. Insight into the illness was fair, with recognition of the need for treatment. Judgment was intact regarding personal care but impaired in terms of complex decision-making. On physical examination, the patient appeared well-nourished and hydrated. Vital signs were within normal limits. A congenital right eyelid ptosis was noted. No evidence of neurological deficits was found.\u003c/p\u003e \u003cp\u003eBlood analyses upon admission revealed minor, clinically insignificant variances in creatinine levels (58 \u0026micro;mol/L, reference range: 62 to 106 \u0026micro;mol/L), uric acid (524 \u0026micro;mol/L, reference range: 143 to 416 \u0026micro;mol/L), and sedimentation rate (14 mm/h, reference range: 2 to 12 mm/h), while all other parameters fell within normal limits. Upon admission, therapy adjustment commenced, involving a gradual reduction in the daily dosage of valproate and the introduction of lithium. Persistent insomnia prompted the medical team to administer additional peroral therapy for several consecutive nights, consisting of 15 mg of midazolam, followed by 10 mg of zolpidem, 50 mg of quetiapine, and 10 mg of diazepam. Nevertheless, the patient experienced less than two hours of continuous sleep.\u003c/p\u003e \u003cp\u003eFollowing the intramuscular administration of 50 mg of chlorpromazine in the evening therapy for persistent and refractory insomnia fourth day upon admission, the patient exhibited agitation, failed to establish verbal communication despite being awake, displayed disorganized behavior, and presented with pale, diaphoretic skin in the morning. Vital signs recorded included a body temperature of 37.7\u0026deg;C, blood pressure of 150/90 mmHg, and blood glucose level of 8.4 mmol/L. Rigidity and hypertonicity were observed in the arm and neck muscle groups bilaterally. During the physical examination, the previously non-verbal patient suddenly began conversing fluently in English (which he had learned during childhood but had never spoken outside of school), primarily inquiring about the hospital\u0026rsquo;s location and the reason for his presence. This episode lasted approximately 5 minutes, after which the patient reverted to non-communication with the medical staff.\u003c/p\u003e \u003cp\u003eDue to suspicion of developing NMS, all previous psychopharmacotherapy was discontinued. The following treatments were administered: 500 ml of 0.9% NaCl solution with vitamin B and C intravenously, 5 mg of biperiden hydrochloride intramuscularly, and 2.5 mg of lorazepam orally three times a day. A blood sample was sent for urgent laboratory analysis, which confirmed the suspicion of NMS showing elevated creatine phosphokinase (CPK) values at 1662 IU/L (reference range: 20 to 200 IU/L) and leukocytosis at 9.5x10^9/L (reference range: 4.0 to 9.0 x10^9/L). Additionally, there were several other clinically less significant deviations: sodium 133.0 mmol/L (reference range: 136.0 to 145.0 mmol/L), chlorides 96.0 mmol/L (reference range: 98.0 to 107.0 mmol/L), uric acid 435 \u0026micro;mol/L (reference range: 143 to 416 \u0026micro;mol/L), AST 84 IU/L (reference range: \u0026lt;40 IU/L), CRP 10.52 mg/L (reference range: \u0026lt;5 mg/L), and direct bilirubin 5.7 \u0026micro;mol/L (reference range: \u0026lt;5 \u0026micro;mol/L).\u003c/p\u003e \u003cp\u003eSeveral hours after the administration of the parenteral therapy the patient felt better. On the same day, he was thoroughly examined by an internist. Subjectively, he complained of difficulty speaking, slowness, and instability while walking. Objectively, he was eupneic, obese, subfebrile (body temperature 37.5\u0026deg;C), and his extremities were without swelling. Lung auscultation revealed normal breath sounds, and heart auscultation revealed clear tones without murmurs. His blood pressure was 125/80 mmHg. An ECG showed sinus rhythm with a heart rate of 100 beats per minute, and the ST and T waves were unremarkable. The therapy was adjusted to include bisoprolol 2.5 mg in the morning and amoxicillin/clavulanic acid (875 mg/125 mg) twice daily, along with the parenteral administration of one liter of infusion solution daily (0.9% NaCl with vitamins C and B). After two days, repeat blood biochemical analyses showed a slight decrease in CPK levels (1416 IU/L). For a detailed comparative presentation of the blood laboratory analysis results, see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparative presentation of blood analysis results\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory analysis\u003c/p\u003e \u003cp\u003e(reference range)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUpon admission \u0026ndash; day 0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSuspicion of NMS \u0026ndash; day 5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFollow-up - day 7\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFollow-up - day 11\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFollow-up - day 12\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSodium (136.0-145.0 mmol/l)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e144.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e133.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e138.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e136.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e140.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChlorides (98.0-107.0 mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e96.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e102.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e101.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e104.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCreatinine (62\u0026ndash;106 umol/l)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e58\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e57\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e53\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e56\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrea (1.7\u0026ndash;8.3 mmol/l)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUric acid (143\u0026ndash;416 \u0026micro;mol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e524\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e435\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e468\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e403\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e373\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAST (\u0026lt;\u0026thinsp;40 IU/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e84\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e111\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eALT (\u0026lt;\u0026thinsp;41 IU/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e46\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDirect bilirubin (\u0026lt;\u0026thinsp;5 \u0026micro;mol/L\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e5.7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlbumins (30\u0026ndash;50 g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e51\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCPK (20\u0026ndash;200 IU/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1662\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e1416\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e344\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e212\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal leukocyte count (4.0\u0026ndash;9.0 x10^9/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e9.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePlatelets (150\u0026ndash;350 x10^9/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e295\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e360\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e358\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP (\u0026lt;\u0026thinsp;5 mg/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e10.52\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSedimentation (2\u0026ndash;12 mm/h)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e14\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cem\u003eNote: Only the laboratory analysis results that deviated from the reference values at any point during the monitoring are shown; \u0026ldquo;/\u0026rdquo; \u0026ndash; the analysis was not performed at the given time point.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e- Insert Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e here -\u003c/p\u003e \u003cp\u003eOver the following days, two additional internal medicine check-ups were conducted with repeated blood laboratory analyses (refer to Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e for details). Parenteral and oral rehydration therapy continued, accompanied by ongoing monitoring of vital signs. The patient remained afebrile, with pulse and blood pressure consistently within normal ranges. Consequently, antibiotics were discontinued after one week, along with bisoprolol. The patient was also examined by a neurologist and an EEG recording was performed. Besides the congenital anomaly of the left eyeball the neurological exam was unremarkable. EEG showed low amplitude basic activity and drug-induced acceleration, without pathological changes. A brain MRI was indicated to be performed after discharge from hospital treatment. Upon stabilization, a psychological assessment was also conducted, indicating low-average intellectual functioning (total IQ 79, verbal IQ 78, performance IQ 77). The personality inventory showed self-defeating and depressive personality dimensions, high level of internal anxiety, and persistent vulnerability to disorganization in response to daily life stressors.\u003c/p\u003e \u003cp\u003eConcurrently, the patient's mental state gradually improved, with persistent insomnia and evening irritability as the sole remaining symptoms. Following stabilization of the laboratory parameters, quetiapine was gradually initiated in the evening (dose gradually increased to 200 mg), followed by reduction in the daily lorazepam dose. This resulted in normalized sleep patterns and initial remission upon discharge.\u003c/p\u003e"},{"header":"Discussion and conclusions","content":"\u003cp\u003eNMS, initially termed \u0026ldquo;fatal hyperpyrexia\u0026rdquo; in 1956 shortly after the introduction of chlorpromazine [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] (\u003cem\u003eAYD, 1956\u003c/em\u003e), is a rare condition affecting approximately up to 3% of patients using antipsychotic drugs [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. First-generation antipsychotics pose a higher risk compared to newer agents due to their affinity towards D2 receptors. Other established risk factors include dehydration, malnutrition, parenteral administration of antipsychotics, preexisting brain lesions, substance use disorders, and a history of NMS. Treatment involves immediate discontinuation of the offending agent with supportive care, and specific pharmacological interventions (i.e. dantrolene, bromocriptine) recommended for severe cases [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Re-initiating antipsychotic therapy should be approached cautiously, starting with low-potency agents at low doses after at least two weeks of NMS resolution, gradually titrating to achieve therapeutic effect.\u003c/p\u003e \u003cp\u003eThe pathophysiology of NMS is complex and not fully understood. Most symptoms arise from a sudden reduction in central dopaminergic activity, either from D2 receptor blockade or abrupt withdrawal of D2 receptor stimulation. Mortality rates can reach up to 10%, primarily due to autonomic nervous system instability and complications such as rhabdomyolysis, disseminated intravascular coagulation, acute respiratory or kidney failure, sepsis, and other systemic issues [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Prompt recognition is crucial to prevent adverse outcomes. NMS should be suspected when a cluster of symptoms related to autonomic instability, neuromuscular abnormalities, and central nervous system dysfunction gradually appears in patients treated with medications affecting central dopaminergic neurotransmission. However, atypical presentations can occur.\u003c/p\u003e \u003cp\u003eTo our best knowledge, nine documented cases of foreign language syndrome exist in the literature to date [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Common features observed in all cases, including ours, include male gender, Caucasian ethnicity, switching from a native language to a second language acquired later in life (rather than being bilingual from the outset), and limited proficiency in the acquired language. The observation that all reported postoperative foreign language syndrome involved males, as well as our NMS-associated case, may be coincidental. However, another plausible explanation related to sex differences in the brain could also be considered. Namely, language lateralization tends to be more pronounced in males, with women often showing bilateral activation during speech while men typically exhibit left hemisphere dominance [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Half of the cases, including ours, did not recall speaking the foreign language during the episode. A notable feature in most cases is the lack of self-awareness exhibited by patients during transient fixation episodes. Some deny being able to speak their non-native language at all, and most, including our case, are surprised to learn they had spoken it during the episode. Previous reports also document two cases of recurrence: one postoperatively after awakening from anesthesia, and another during severe alcohol intoxication. Both alcohol and anesthetics impact cerebral blood flow and glucose metabolism, with anesthetics having a more suppressive effect. Hypoglycemia has been proposed as a possible contributing factor [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Evidence also suggests that global transient cognitive deficits may be worsened with hypoglycemia.\u003c/p\u003e \u003cp\u003eForeign language syndrome, an exceptionally rare manifestation observed in NMS and other brain conditions, challenges our understanding of language processing in the brain. The precise pathophysiology of this intriguing phenomenon remains uncertain, particularly whether it represents a distinct syndrome on its own or a phenotype of another syndrome such as delirium. Salamah et al. (2022) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] proposed that foreign language syndrome might represent a delirium phenotype, rather than a distinct entity. This hypothesis is supported by findings of impaired language functions in delirious patients compared to cognitively unimpaired individuals, including spontaneous speech production, word quantity, speech content, and language comprehension [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Considering these hypotheses and our case presentation, it is reasonable to assume that delirium could be a common underlying factor in the manifestation of foreign language syndrome in our patient with NMS and in postoperative cases documented in previous literature.\u003c/p\u003e \u003cp\u003eLanguage remains one of humanity's most impressive cognitive abilities, yet the mechanisms underlying its processing in the brain remain largely unknown. The anatomical areas responsible for native and foreign languages are not fully understood. The neuropsychological rationale for the substitution of a native language with a later-acquired one suggests that the native language is partly acquired and stored through implicit memory systems in subcortical regions such as the basal ganglia and cerebellum. In contrast, second languages learned through explicit rules are thought to be represented broadly across the cerebral cortex [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Functional brain imaging studies provide evidence of distinct cortical areas associated with native and later-acquired languages [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Studies also indicate that these areas may overlap in early bilinguals (i.e. who learned a second language before the age of 5), whereas late bilinguals exhibit distinct regions for each language [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrevious theories about the causes of transient fixation on a non-native language under general anesthesia suggest that the separation between native and non-native languages allows differential effects of anesthesia on the brain, with one language faculty remaining active while the other is suppressed [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Possible mechanisms include suppression of brain areas responsible for native language abilities, whether due to anesthesia or another underlying pathophysiological mechanism, leading to a language switch and compensation from activation of second language centers in different brain regions [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis case report should be considered in light of its limitations. The findings are based on a single patient, limiting their generalizability to a broader population and potentially not reflecting the experiences of other individuals with NMS or foreign language syndrome. Key details about previous treatments and psychiatric history were unavailable due to the destruction of medical records, which may impact the accuracy of the reported associations and the interpretation of the patient's condition. Additionally, the patient\u0026rsquo;s use of multiple medications and complex psychiatric history introduce confounding factors, complicating the attribution of symptoms solely to NMS or foreign language syndrome. Further research involving additional cases is essential to validate and expand upon these findings.\u003c/p\u003e \u003cp\u003eThis case points to opportunities for further research into the neurobiological mechanisms linking NMS with foreign language syndrome, sex-differences in the brain and the role of conditions like delirium in language processing.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCPK\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCreatine phosphokinase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDSM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e5-Diagnostic and Statistical Manual of Mental Disorders\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNMS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeuroleptic malignant syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThe study was conducted in accordance with the Declaration of Helsinki, and the conduct of this study was approved by the ethics committee of the Institute of Mental Health in Belgrade, Serbia\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eConsent for publication was obtained from patient presented in the case-report. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eAll data generated or analysed during this study are included in this published article\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNothing to declare\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e:\u0026nbsp;SAP and NM equally contributed to the analysis and interpretation of the patient data, as well as the literature search. Both authors also played an equal role in writing the manuscript. SAP and NM have reviewed and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDonnet A, Harle JR, Dumont JC, Cherif AA. Neuroleptic malignant syndrome induced by metoclopramide. Biomed Pharmacother. 1991;45(10):461\u0026ndash;2. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0753-3322(91)90048-x\u003c/span\u003e\u003cspan address=\"10.1016/0753-3322(91)90048-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO'Griofa FM, Voris JC. Neuroleptic malignant syndrome associated with carbamazepine. 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J Neurolinguistics. 2015;36:35\u0026ndash;55. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jneuroling.2015.05.001\u003c/span\u003e\u003cspan address=\"10.1016/j.jneuroling.2015.05.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-general-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"agps","sideBox":"Learn more about [Annals of General Psychiatry](http://annals-general-psychiatry.biomedcentral.com/)","snPcode":"12991","submissionUrl":"https://submission.nature.com/new-submission/12991/3","title":"Annals of General Psychiatry","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Neuroleptic malignant syndrome, Foreign language syndrome, Antipsychotic-induced complications, Chlorpromazine, Atypical neurological presentations, Sex-difference","lastPublishedDoi":"10.21203/rs.3.rs-4919126/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4919126/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eForeign language syndrome is rare neuropsychiatric condition which usually follows routine general anesthesia. To the best of our knowledge, the occurrence of foreign language syndrome has not been previously associated with neuroleptic malignant syndrome (NMS) in the existing literature. By documenting the following case, we aim to expand the understanding of NMS's clinical spectrum and highlight the importance of recognizing atypical presentations for prompt diagnosis and effective management.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eA 34-year-old Caucasian male with a history of schizoaffective disorder and multiple psychiatric hospitalizations was admitted for a depressive episode. His condition deteriorated several hours after intramuscular chlorpromazine administration, leading to NMS, characterized by agitation, muscle rigidity, hyperthermia, autonomic instability, typical characteristic laboratory findings, and altered mental status, including foreign language syndrome. Treatment involved discontinuation of prior psychopharmacotherapy, intravenous hydration and medication (biperiden, and lorazepam). The patient showed significant improvement with resolution of NMS symptoms and normalized sleep patterns upon discharge.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eForeign Language Syndrome is a rare phenomenon documented in only nine cases to date, all involving male patients. This report introduces a novel case where Foreign Language Syndrome is associated with NMS in a male patient. This case represents the first documented instance of Foreign Language Syndrome linked to NMS in a male, thereby contributing to the understanding of potential sex-specific mechanisms underlying this condition.\u003c/p\u003e","manuscriptTitle":"Bilingual Side Effect: A Case of Foreign Language Syndrome Following Chlorpromazine-Induced Neuroleptic Malignant Syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-12 07:37:19","doi":"10.21203/rs.3.rs-4919126/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-05T14:33:56+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-24T01:47:43+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-10T14:49:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"249601971399585228607873684401655491712","date":"2024-11-07T14:32:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-05T07:34:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"106241601716863075786225913878421879209","date":"2024-11-05T07:09:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"103210363731843059238850407016968910597","date":"2024-11-04T12:50:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"106576178444233010362466356844697266181","date":"2024-11-04T01:43:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"140725316086548988182938533915446216466","date":"2024-11-02T12:58:07+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-02T10:20:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-15T13:29:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-15T13:29:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of General Psychiatry","date":"2024-08-15T11:52:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-general-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"agps","sideBox":"Learn more about [Annals of General Psychiatry](http://annals-general-psychiatry.biomedcentral.com/)","snPcode":"12991","submissionUrl":"https://submission.nature.com/new-submission/12991/3","title":"Annals of General Psychiatry","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"56e6ce23-98e9-4bd3-b355-03e1aa0a2d76","owner":[],"postedDate":"September 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-01-06T15:59:56+00:00","versionOfRecord":{"articleIdentity":"rs-4919126","link":"https://doi.org/10.1186/s12991-024-00538-6","journal":{"identity":"annals-of-general-psychiatry","isVorOnly":false,"title":"Annals of General Psychiatry"},"publishedOn":"2025-01-02 15:57:12","publishedOnDateReadable":"January 2nd, 2025"},"versionCreatedAt":"2024-09-12 07:37:19","video":"","vorDoi":"10.1186/s12991-024-00538-6","vorDoiUrl":"https://doi.org/10.1186/s12991-024-00538-6","workflowStages":[]},"version":"v1","identity":"rs-4919126","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4919126","identity":"rs-4919126","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}