Case report: post COVID-19 encephalopathy and oral cenesthopathy

Abstract

Post-COVID-19 encephalopathy is a neurological complication characterized by cognitive impairment, memory loss, and other neuropsychiatric symptoms in COVID-19 survivors. Oral cenesthopathy, a rare somatic delusion characterized by unusual oral sensations without physical findings, is typically associated with affective disorders and schizophrenia. This case report describes a 73-year-old female who developed post-COVID-19 encephalopathy, presenting initially with cognitive decline, followed by major depression and oral cenesthopathy 16 months after the infection. Comprehensive investigations excluded autoimmune encephalitis, Creutzfeldt-Jakob disease, and other structural or vascular abnormalities. Treatment with Aripiprazole and Carbamazepine resulted in partial improvement, though symptom control was limited by medication side effects. This case represents a rare presentation of long COVID syndrome, highlighting the complex neuropsychiatric sequelae of COVID-19. Further research is needed to explore the pathophysiology, treatment strategies, and long-term impacts of such manifestations.

Background

COVID-19 survivors suffer from neurological and psychiatric sequelae such as cognitive impairment, memory loss, paresthesia, anxiety, depression, and sleep disturbances [1]. Long-term neurodegenerative effects have been reported in COVID-19 survivors; however, the pathophysiology remains largely unknown [2]. Here, we presented a case with post COVID-19 encephalopathy manifested as marked cognitive decline, followed by major depression and oral cenesthopathy, a rare somatic delusion known to be related to affective disorders and schizophrenia in the literature [3], 16 months after COVID-19 infection.

Case presentation

Mrs. P, a 73-year-old female, first presented to our Psychiatric Outpatient Department with a history of hypertension and no family history of psychiatric disorders. At age 71, she contracted COVID-19, which was followed by a progressive decline in cognitive function. She was subsequently admitted to the Neurology ward under the initial impression of autoimmune encephalitis or Creutzfeldt-Jakob disease (CJD). Nonetheless, extensive investigations for common causes of autoimmune encephalitis, including antinuclear antibody (ANA), NMDA, AMPA, GABA-b, caspr, LGI-1, and DPPx, yielded negative results. Brain Magnetic Resonance Imaging (MRI) revealed old lacunar infarctions at the right centrum semiovale and the left basal ganglion but did not demonstrate the classic cortical ribbon signs indicative of CJD. Electroencephalography (EEG) showed diffuse cortical dysfunction. In the absence of evidence supporting autoimmune encephalitis or CJD, post COVID-19 encephalopathy was considered the underlying etiology for her progressive cognitive decline. 16 months post-infection, Mrs. P developed a major depressive episode characterized by anhedonia, insomnia, decreased appetite, general fatigue, feeling of worthlessness and pervasive negative thoughts. In addition to these core mood symptoms, she reported unusual oral sensations, describing them as “small teeth growing within the gums in my mouth” and “these teeth are squeezing and pulling around, and when I tilt my head, they are coming out of my ear”. Despite these vivid descriptions, she did not report specific taste disturbances such as dysgeusia or ageusia. These sensations prompted multiple dental consultations, none of which identified significant abnormalities. Trigeminal neuralgia was suspected, and Carbamazepine was prescribed, but the response was minimal. Mrs. P was admitted to our psychiatric ward with a working diagnosis of major depression with oral cenesthopathy and post COVID-19 encephalitis. She denied other psychotic symptoms such as auditory or visual hallucination, persecutory or reference delusion, or a history of manic episodes. Comprehensive laboratory work up and physical examination upon admission were unremarkable. Repeat EEG showed no evidence of cortical dysfunction and Magnetic Resonance Angiography (MRA) excluded vascular loop syndrome or mass lesions along the bilateral trigeminal nerve courses. Comprehensive neuropsychological assessment revealed significant cognitive impairment, as indicated by Mini-Mental State Examination (MMSE) score of 15/30 and Clinical Dementia Rating (CDR) 1. Pharmacological treatment included Aripiprazole 5 mg and Carbamazepine 600 mg were prescribed. This regimen resulted in partial symptom improvement. While Mrs. P remained convinced of the uncontrollable teeth movement in her mouth, the intensity of her discomfort diminished, and she appeared less agitated and depressed. An attempt to titrate Aripiprazole dosage to 7.5 mg for enhanced symptom control led to unsteady gait and a subsequent fall, necessitating a reduction back to 5 mg. Mrs. P was discharged with partial improvement under the same regimen of Aripiprazole 5 mg and Carbamazepine 600 mg daily.

Discussion

To the best of our knowledge, this is the first case report documenting a patient who initially presented with post-COVID-19 encephalopathy and subsequently developed major depression with oral cenesthopathy 16 months later, representing a rare manifestation of long COVID syndrome.

Long COVID is a multisystemic illness affecting at least 10% of individuals following COVID-19 infection. It is characterized by a wide range of persistent symptoms across multiple organ systems, often lasting months or years [1]. Neurological manifestations are particularly prevalent and persistent in long COVID patients, with the highest prevalence observed within the first 6 months post-infection. Common neurological symptoms include cognitive dysfunction and paresthesia [3]. Cognitive dysfunction is often one of the earliest neurological manifestations, while paresthesia is characterized by abnormal sensations such as tingling, numbness, or a “pins and needles” feeling, typically affecting extremities. Although the exact mechanism of paresthesia remains unclear, it is hypothesized to involve nerve damage or inflammation [4]. In Mrs. P’s case, the significant cognitive decline observed post-COVID aligns with the literature on long COVID. However, her later development of abnormal oral sensations with delusional interpretations diverges from typical post-COVID paresthesia and is better described as oral cenesthopathy. Oral cenesthopathy is defined by unusual sensations without corresponding abnormal findings. These sensations may include feeling of a foreign body in the mouth, excessive mucus secretion, slimy or sticky sensations, or more complex perceptions such as squeezing or pulling sensations. Other reported symptoms include sensations of coils or wires, gas or bubbles, misalignment or twisting sensations in the gums, feelings of something about to spout out or taste disturbance [5, 6]. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), oral cenesthopathy is classified under delusional disorder, somatic type. One previous study has noted oral cenesthopathy predominantly occur in elderly female patients and may be associated with dental treatments during the acute phase of depressive episodes [5]. Additionally, oral cenesthopathy has been linked to conditions such as schizophrenia, depression, and burning mouth syndrome [5, 7]. These symptoms are often chronic, challenging to treat, and significantly impact patients’ quality of life, affecting eating, speaking, and social interactions.

One prior case report documented the co-occurrence of cognitive decline and oral cenesthopathy in a patent with dementia with Lewy Bodies (DLB) [7]. The diagnosis of DLB requires the presence of dementia alongside core clinical features including fluctuating cognition, recurrent visual hallucinations, REM sleep behavior disorder (RBD), and spontaneous parkinsonism. Supportive features include sensitivity to antipsychotic agents, severe autonomic dysfunction and systematized delusions [8]. In Mrs. P’s case, the absence of visual hallucinations, RBD, or parkinsonism rendered a diagnosis of DLB less likely. Furthermore, diagnostic tools such as dopamine transporter scans, 123 iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, and polysomnographic were not pursued, as clinical features did not strongly suggest DLB.

The mechanisms linking post-COVID encephalopathy to oral cenesthopathy remain unclear, but persistent neuroinflammation and immune dysregulation may play a role [1, 3, 5]. Long COVID is associated with prolonged microglial activation, elevated pro-inflammatory cytokines, and structural brain changes, which can disrupt sensory processing and lead to abnormal bodily perceptions [1, 3]. Functional imaging studies in cenesthopathy patients demonstrate hypoperfusion in the prefrontal cortex and hyperperfusion in the somatosensory cortex, patterns potentially exacerbated by COVID-related cytokine storms [6, 9]. Additionally, dopaminergic dysfunction has been implicated, as evidenced by the partial efficacy of dopamine-modulating agents like aripiprazole [6, 10]. In Mrs. P’s case, the progression from post-COVID encephalopathy to oral cenesthopathy may reflect the combined impact of persistent neuroinflammation, sensory misinterpretation, and comorbid depression [5, 6]. Similar cases have been reported in neuropsychiatric disorders where sensory disturbances evolve into somatic delusions [6, 9]. Further research is needed to clarify how post-COVID neuroinflammation alters sensory perception and to explore targeted treatments for oral cenesthopathy in long COVID patients.

Treatment of oral cenesthopathy remains challenging. One retrospective chart review identified several medications/therapy with potential efficacy, including paroxetine [11] fluvoxamine [9] amitriptyline [9, 12], sulpiride [12], risperidone [9], olanzapine [9], aripiprazole [6] and electroconvulsive therapy (ECT) [13]. These treatments primarily target underlying mood disorders that may exacerbate abnormal oral sensations. However, only 36% of patients demonstrated clinically significant improvement after 6 months of pharmacotherapy [6], with aripiprazole being the most effective agent [6]. Aripiprazole, a partial dopamine D2 receptor agonist, has demonstrated efficacy in managing psychiatric conditions associated with delusional symptoms. In Mrs. P’s case, the use of aripiprazole at 5 mg/day exceeded the mean dosage of 1.52 mg/day reported in previous cenesthopathy cohorts [6], reflecting the severity of her delusional preoccupation and comorbid depression. However, dose escalation was limited by side effects, underscoring the challenges of pharmacotherapy in elderly patients with post-COVID encephalopathy. Notably, the average dose of aripiprazole for delusional disorders is 11.1 mg/day, with a range of 1.5–30 mg/day as reported in one recent systematic review [10]. The relatively low dose used in Mrs. P’s treatment may suggest her symptoms were more likely attributed to underlying central nervous system pathology, such as post-COVID-19 encephalopathy, rather than a primary psychiatric disorder.

On the other hand, Carbamazepine, prescribed for suspected trigeminal neuralgia, demonstrated minimal efficacy in this case. While carbamazepine is effective in managing neuropathic pain and mood lability, its limited impact prompted a reevaluation of the diagnosis in this case, leading to the identification of oral cenesthopathy as the underlying condition. Its role in Mrs. P’s case may extend to mitigating neuropathic pain mechanisms potentiated by COVID-related neuroinflammation [14].

Conclusion

This case highlights a rare presentation of post-COVID neuropsychiatric manifestations, including cognitive impairment, depression, and oral cenesthopathy. The findings underscore the need for further research to delineate the long-term neurological and psychiatric sequelae of long COVID, as well as the underlying biological mechanisms, such as inflammation and neurotransmitter dysregulation. Additionally, more studies are warranted to explore effective treatment strategies for neuropsychiatric symptoms in long COVID patients.

Author contributions

JIW wrote the main manuscript text. SHL and PJC revised and edited the manuscript. All authors read and approved the final manuscript.

Funding

Not applicable.

Data availability

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Declarations

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Competing interests

The authors declare no competing interests.