Bilingual side effect: a case of foreign language syndrome following chlorpromazine-induced neuroleptic malignant syndrome

Abstract

Background

Foreign language syndrome is a rare neuropsychiatric phenomenon typically following general anesthesia. To date, foreign language syndrome has not been associated with neuroleptic malignant syndrome (NMS) in the literature. This case aims to broaden the clinical understanding of NMS by presenting an atypical manifestation of foreign language syndrome and emphasizing the need for prompt recognition of such presentations for accurate diagnosis and management.

Case presentation

A 34-year-old Caucasian male with a history of schizoaffective disorder and recurrent psychiatric hospitalizations was admitted for a depressive episode. His condition worsened hours after the administration of intramuscular chlorpromazine, leading to NMS characterized by agitation, muscle rigidity, hyperthermia, autonomic instability, abnormal laboratory findings, and altered mental status, including foreign language syndrome. Management included the discontinuation of the prior psychopharmacotherapy, intravenous hydration, and medications (biperiden, lorazepam). The patient showed significant improvement, with resolution of NMS symptoms and normalized sleep patterns by the time of discharge.

Conclusion

Foreign language syndrome is an exceptionally rare occurrence, with only nine documented cases to date, all involving male patients. This case presents a novel instance of foreign language syndrome in the context of NMS in a male patient, providing insight into the potential sex-specific mechanisms underlying this rare phenomenon. This case adds valuable evidence to the understanding of the clinical spectrum of NMS and highlights the importance of recognizing atypical presentations in managing patients with neuropsychiatric conditions.

Background

Neuroleptic Malignant Syndrome (NMS) is a rare, life-threatening idiosyncratic reaction primarily triggered by dopamine antagonists, including first-generation and second-generation antipsychotics, as well as other drugs that affect central dopaminergic neurotransmission. NMS typically presents with a combination of major symptoms such as muscle rigidity, hyperthermia, and diaphoresis in the context of exposure to dopamine antagonists within 72 h before the onset of symptoms, alongside minor symptoms, including autonomic instability, altered mental status and characteristic laboratory findings (primarily elevated levels of creatine phosphokinase (CPK) and leukocytosis) [1]. It is crucial that these symptoms are not attributed to another substance, neurological disorder, or underlying medical condition for an accurate diagnosis of NMS [4]. While high-potency first-generation antipsychotics are most commonly associated with NMS, it can also be induced by low-potency antipsychotics and even clozapine, as well as other medications like certain antidepressants, mood stabilizers, and antiemetics [2,3,4]. According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), NMS is classified as a drug-induced movement disorder with a wide range of clinical manifestations [1]. However, despite the well-documented clinical features and risk factors, there is limited understanding of its pathophysiology and potential associations with other phenomena.

Foreign language syndrome, characterized by an unexpected switch to a non-native language, has been documented in only a few cases within the current literature, typically following general anesthesia in the immediate postoperative period [5,6,7,8,9,10,11]. While the exact cause of this phenomenon remains unclear, it has been reported as a temporary condition with spontaneous recovery. In contrast to [12] foreign accent syndrome, which involves a change in speech rhythm, foreign language syndrome involves a full transition to a second language, with the patient often unaware of the switch. The association between NMS and foreign language syndrome has not been explored in the current literature.

This case report aims to fill this gap by reporting the first known instance of foreign language syndrome occurring in the context of chlorpromazine-induced NMS. The purpose of this report is to examine the potential connection between these two rare phenomena, offering insights into the neurobiological mechanisms that may underlie their co-occurrence.

Case presentation

A 34-year-old Caucasian male, whose native language is Serbian and who completed primary school as his highest level of education, was admitted to the Clinical Department for Psychotic Disorders at the Institute of Mental Health in Belgrade, Serbia in July 2024, where his psychiatric treatment had begun two months earlier. Upon admission, the patient reported experiencing marked apathy, low energy, significantly diminished motivation, tearfulness and persistent insomnia over the past six months. He struggled with daily tasks, neglecting both his agricultural responsibilities and familial duties.

Upon initial assessment, the patient appeared well-groomed but slightly older than his stated age. He was cooperative but demonstrated slight psychomotor retardation, with decreased spontaneous movements and reduced facial expressions. His speech was slow, with a monotonous tone and a prolonged reaction time. He appeared anxious, with signs of restlessness and a fine hand tremor. His mood was moderately to severely depressed, with thoughts dominated by nihilistic ideation, though he denied any suicidal or self-harm thoughts. There were no delusions, hallucinations, or obsessive-compulsive symptoms. His thought processes were logical but slowed, and his concentration was impaired, evidenced by difficulties with simple calculations. Immediate and recent memory was mildly impaired, and his intelligence was estimated to be in the low-average range. He demonstrated fair insight into his illness, recognizing the need for treatment, although his judgment regarding complex decision-making was impaired. On physical examination, the patient appeared well-nourished and hydrated. Vital signs were within normal limits. A mild unilateral (left) congenital blepharoptosis was noted. No evidence of neurological deficits was found.

A significant portion of the patient’s psychiatric medical records pertaining to previous treatments were unavailable upon admission due to their destruction during a prior exacerbation. Therefore, the history of present illness, past treatments, and medications, as well as the family history, were derived from the remaining available records.

The patient’s first psychiatric symptoms appeared at the age of 14, including obsessive thoughts, compulsions, and aggressive behavior. He was diagnosed with schizoaffective disorder, leading to the initiation of lithium and clozapine therapy. Throughout adolescence, the patient was hospitalized multiple times due to self-discontinuation of medications, resulting in recurrent decompensations. At the age of 22, after an episode of aggression, the patient was started on olanzapine, valproate, and diazepam. Despite periods of stability, medication tapering led to recurrent aggressive outbursts, resulting in three more hospitalizations between the ages of 28 and 33. His most recent therapy prior to admission described in this case report consisted of levomepromazine and valproate.

The patient denied any history of head injuries, loss of consciousness, or serious somatic illnesses, but acknowledged occasional alcohol consumption over the past fifteen years, sometimes to the point of intoxication. The frequency and amount of alcohol use should be interpreted cautiously due to his tendency to minimize intake. There was no history of other substance abuse. His family history revealed psychiatric conditions, including a brother with intellectual disabilities and a paternal grandfather who died by suicide.

Based on the chief complaints, the history of present illness, and the mental status examination, a diagnosis of a depressive episode in the context of schizoaffective disorder was made, and a plan for further complementary diagnostic work-up and modification of therapy was established. Initial blood analyses revealed minor, clinically insignificant variances in creatinine levels, uric acid, and sedimentation rate, while all other parameters were within normal limits (see Table 1). 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.

Table 1 Comparative presentation of blood analysis results

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. He inquired with visible anxiety, asking, “Where am I… What hospital is this… Why am I here… What’s wrong with me?” His tone was filled with confusion and distress, and he appeared highly anxious, exhibiting physical signs of anxiety such as pallor and profuse sweating. This episode lasted only about five minutes, after which the patient reverted to non-communication with the medical staff, returning to his previous state of silence. It was only after the episode had ended that we learned from the patient that his knowledge of English was limited to what he had learned in primary school and through watching cartoons. He had never used the language in practical settings after school, as he lived in a rural area in Serbia and had never travelled abroad.

Considering the presence of several major and minor DSM-5 criteria for NMS, including muscle rigidity, hyperthermia, and diaphoresis in the context of exposure to dopamine antagonists within 12 h prior to the onset of symptoms, along with autonomic instability and altered mental status, a suspicion of NMS was raised in this patient. Consequently, all previous psychopharmacotherapy was discontinued, and the following treatments were administered: 500 ml of 0.9% sodium chloride 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 characteristic laboratory findings - elevated CPK values at 1662 IU/L (reference range: 20 to 200 IU/L) and leukocytosis at 9.5 × 10^9/L (reference range: 4.0 to 9.0 × 10^9/L). Additionally, there were several other clinically less significant deviations (see Table 1).

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 electrocardiogram 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% sodium chloride 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 1.

Over the following days, two additional internal medicine check-ups were conducted with repeated blood laboratory analyses (refer to Table 1 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 the findings were unremarkable, except for the noted presence of mild unilateral (left) congenital blepharoptosis without visual disturbance. An electroencephalogram recording was also performed, which showed low amplitude basic activity and drug-induced acceleration, without pathological changes. A brain magnetic resonance imaging was indicated to be performed after discharge from hospital treatment.

Upon stabilization, a psychological assessment was also conducted, indicating low-average intellectual functioning (total intelligence quotient (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 only remaining symptoms. After stabilizing laboratory parameters, quetiapine was gradually introduced in the evening, with the dose gradually increasing to 200 mg. The daily lorazepam dose was then reduced. This led to normalized sleep patterns and initial remission upon discharge. Details regarding the patient’s follow-up after discharge were not available, as the patient failed to attend the scheduled outpatient appointment.

Discussion and conclusions

NMS, first described in 1965 as “fatal hyperpyrexia”, following the introduction of chlorpromazine [13], is a rare but potentially life-threatening condition affecting 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 dopamine D2 receptors. Other established risk factors include dehydration, malnutrition, parenteral administration of antipsychotics, pre-existing brain lesions, substance use disorders, and a history of NMS. Treatment involves immediate discontinuation of the offending agent, supportive care, and specific pharmacological interventions such as dantrolene and bromocriptine in severe cases [16]. Re-initiation of antipsychotic therapy should be approached cautiously, with low-potency agents at low doses after a minimum two-week resolution period, gradually titrating to achieve a therapeutic effect.

The pathophysiology of NMS remains complex and incompletely understood. Most symptoms arise from a sudden reduction in central dopaminergic activity, either from dopamine D2 receptor blockade or abrupt withdrawal of dopamine stimulation. Mortality rates can reach 10%, primarily due to autonomic instability and complications such as rhabdomyolysis, disseminated intravascular coagulation, acute respiratory or renal failure and sepsis [17]. Prompt recognition and intervention are critical to prevent adverse outcomes. NMS should be suspected when a cluster of symptoms including autonomic instability, neuromuscular abnormalities, and central nervous system dysfunction appears in patients treated with medications that affect dopaminergic neurotransmission. However, atypical presentations can occur, as observed in the case presented here.

To our knowledge, there are only nine documented cases of foreign language syndrome to date [5] (see Table 2). Common features across these cases, including ours, include male gender, Caucasian ethnicity, switching from a native language to a second language learned later in life (rather than being bilingual from the outset), and limited proficiency in the acquired language.

Table 2 Summary of reported cases of Foreign Language Syndrome

The observation that all reported cases, including ours, involved males may be coincidental. However, sex-differences in brain lateralization could provide an alternative explanation. Research has shown that language lateralization tends to be more pronounced in males, with left hemisphere dominance during speech, whereas women often exhibit bilateral activation [18, 19]. Notably, half of the cases, including ours, did not recall speaking the foreign language during the episode, and many patients were surprised to learn they had done so. The lack of self-awareness during these transient episodes is a common feature.

Previous reports have also documented two cases of recurrence of foreign language syndrome: one postoperatively after 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, as it can exacerbate global cognitive deficits [6].

The exact pathophysiology of foreign language syndrome. remains uncertain. It may represent a delirium phenotype rather than a distinct syndrome, as suggested by Salamah et al. (2022) [5]. This hypothesis is supported by findings of impaired language functions in delirious patients, such as disrupted speech production and comprehension [20]. The hypothesis that delirium may underlie foreign language syndrome is plausible, as it could contribute to transient cognitive changes, including the temporary switch to a non-native language.

Language remains one of humanity’s most impressive cognitive abilities, yet the mechanisms underlying its processing in the brain remain largely unknown. The brain areas responsible for native and foreign language processing are not fully understood, but studies suggest that the native language is often represented in subcortical regions such as the basal ganglia and cerebellum, while second languages are stored more broadly across the cerebral cortex [21]. Functional imaging studies show that early bilinguals (i.e. who learned a second language before the age of 5) exhibit overlapping brain regions for both languages, whereas late bilinguals show distinct regions for each [22,23,24]. This distinction may help explain the occurrence of foreign language syndrome, as differential brain activation during episodes of altered consciousness (e.g., under anesthesia or during NMS) could suppress native language centers while activating regions responsible for the second language.

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, which limits the generalizability to a broader population. Additionally, some important medical details were unavailable due to the destruction of records, which may affect the accuracy of reported associations. The patient’s complex psychiatric history and the use of multiple medications introduce confounding factors, complicating the attribution of symptoms solely to NMS or foreign language syndrome. Further research involving additional cases is needed to validate and expand these findings.

In conclusion, this case highlights the need for further investigation into the neurobiological mechanisms linking NMS with foreign language syndrome, as well as the potential role of delirium in the manifestation of this rare phenomenon. It also underscores the importance of understanding sex-differences in brain structure and function in relation to language processing. Further studies are required to better understand the pathophysiology of foreign language syndrome and its relationship with NMS.