Psychiatric presentation in Rasmussen’s encephalitis

Abstract

Rasmussen’s encephalitis (RE) is a rare neurological disorder characterized by drug-resistant focal epilepsy, progressive hemiplegia, and cognitive decline. While the neurological aspects of RE have been extensively studied, its psychiatric manifestations are often overlooked. This case series presents four illustrative cases of RE with prominent psychiatric symptoms. All cases exhibited a combination of longstanding seizures, developmental delays, and recent-onset psychiatric symptoms, including behavioral disturbances, psychotic features, and altered behavior. Neurological examination revealed characteristic findings such as weakness, tremors, and abnormal reflexes, alongside magnetic resonance imaging evidence of hemicerebral atrophy consistent with RE. Treatment involved a multidisciplinary approach including antiepileptic drugs, antipsychotics, and immunomodulatory therapy. Significant improvements were observed in seizure control and psychiatric symptoms following treatment. Psychiatric manifestations in RE are often attributed to seizure activity and immune responses. RE presents a complex clinical picture with both neurological and psychiatric manifestations. This case series highlights the importance of recognizing and managing psychiatric symptoms in RE to provide comprehensive care to affected individuals.

Rasmussen’s encephalitis (RE), described by Theodore Rasmussen et al.[1] in 1958, also called Rasmussen’s syndrome, is a progressive disease characterized by drug-resistant focal epilepsy, progressive hemiplegia, and cognitive decline, with unihemispheric brain atrophy. RE is an extremely rare and chronic brain disorder that mostly affects one side of the brain. It primarily affects children or young adults.[2] The diagnostic standards for RE were initially defined by Bien et al.[3] in the European consensus statement for RE in 2005. In 2013, Olson et al.[4] introduced an extra criterion. While the main focus has traditionally been on epilepsy and neurological decline, its psychiatric manifestations are often overlooked. Psychosis, affective symptoms, and abnormal behavior are rarely reported.[5] Diagnosis involves clinical signs and symptoms, electroencephalogram (EEG), and magnetic resonance imaging (MRI) findings along with detailed neurological examination. The following case series imparts a better understanding toward the psychiatric symptoms rarely present with this disorder [Table 1].

Table 1:

Case series of 4 cases of RE presenting with psychiatric features

Variable	Case 1	Case 2	Case 3	Case 4
Age and sex	23 years/female	15 years/male	33 years/female	21 years/female
Seizure disorder:Type	Focal seizures	GTCS	Focal seizures	Focal seizures
Secondary generalisation	GTCS present since 8 years		GTCS	GTCS
Age of onset	5 years	8 years	5 years	5 months
Total duration of seizures	18 years	7 years	28 years	20 years
Frequency of seizure	2-3 per day to once every 2 weeks	1-2 episodes per week	Once every 5-10 days	Once every 2-3 months
Neurological symptoms	Weakness in left upper and lower limb since the age of 6 years	Left-sided weakness in upper and lower limbs, bilateral resting tremors. Hypertonia and hyperreflexia in the left upper and lower limbs.
Psychiatric symptoms	Singing religious songs, aggressive, abusive behavior, wandering aimlessly, sudden weeping and laughing spells, poor oral intake and disturbed sleep since 7 days	Decreased social and verbal interaction; unprovoked anger outbursts, occasional episodes of smiling with muttering to himself, poor self-care, and a decreased sleep. Since 2 months.	Muttering to self, suspicious particularly toward her family members and inability to care of herself since 15 days.	Disinhibited behavior, aimless wandering, poor self-care, and decreased sleep since 2 months.
Past history	Similar episodes were reported previously twice in last 1 year and lasted for a brief period of around 1-2 months. History of delayed developmental milestone	History of developmental delays in early childhood with a difficult temperament while growing up.		History of delayed developmental milestones in childhood
Mental status examination findings	Conscious and oriented; alert, arousable with ill sustained concentration; untidy, inappropriately dressed, increased psychomotor activity, spontaneous speech with increased volume and decreased reaction time. Mood and affect were labile with an increased range and mobility. Thought process revealed acceleration and increased volubility; content revealed grandiose ideas with few ideas of persecution, Judgment was impaired and insight was Grade 1	Kempt, tidy, conscious and oriented, alert arousable with ill sustained concentration, decreased psychomotor activity with minimal verbal interaction, blunted affect, judgment impaired and insight- Grade 1.	General appearance and behavior was within normal limit. She exhibited hallucinatory behavior but had normal productivity, reaction time, relevant and coherent speech. The mood was alright, the affect was shallow with decreased mobility and communicability. Thought content was suggestive of delusions of reference and ideas of persecution. Second- and third-person auditory hallucinations were present in perception. Judgment was impaired, and insight was Grade 1.	Normal general physical appearance with intact consciousness and orientation. There is a decrease in productivity of speech with increased reaction time. In thought formal thought disorder was present and in perception third person auditory hallucinations were present. Judgement and insight were absent.
MRI findings	Mild diffuse uniform hemicerebral atrophy, involving right cerebral hemisphere with ex vacuo dilatation of the right lateral ventricle [Figure 1].	Diffuse right hemicerebral atrophy, with volume loss and ex vacuo dilatation of the right lateral ventricle [Figure 2].	Unilateral cortical atrophy predominantly affecting the left cerebral hemisphere, with more pronounced involvement of left capsuloganglionic region and left fronto-parietal lobes [Figure 3].	Patchy areas of T2 hyperintensity showing suppression on FLAIR in left fronto parieto temporal lobes with adjacent gliosis causing ex vacuo dilatation of adjacent sulcal spaces, body of ipsilateral lateral ventricle and ipsilateral sylvian fissures [Figure 4]
Treatment
Antiepileptics	Valproate	Valproate	Valproate	Valproate
Antipsychotics	Risperidone	Olanzapine	Risperidone	Risperidone
Response	Seizures controlled Psychiatric features showed good response	Seizures controlled Psychiatric features showed good response	Seizures controlled and behavior improved	Seizures controlled and behavior improved

Figure 1.

MRI showing mild diffuse uniform hemicerebral atrophy, involving right cerebral hemisphere with ex vacuo dilatation of the right lateral ventricle

Figure 2.

MRI showing diffuse right hemicerebral atrophy, with volume loss and ex vacuo dilatation of the right lateral ventricle

Figure 3.

MRI showing unilateral cortical atrophy predominantly affecting the left cerebral hemisphere, with more pronounced involvement of the left capsuloganglionic region and left fronto-parietal lobes

Figure 4.

MRI showed patchy areas of T2 hyperintensity showing suppression on FLAIR in left fronto parieto temporal lobes with adjacent gliosis causing ex vacuo dilatation of adjacent sulcal spaces, body of ipsilateral lateral ventricle, and ipsilateral sylvian fissures

DISCUSSION

Psychiatric manifestations in RE can be attributed to the multiple factors, including seizure activity and immune responses mediated by T-cells. Ongoing seizure activity can directly cause abnormalities in the brain circuits, leading to disturbances in mood, behavior, and cognition. It can also cause temporary alterations in consciousness, hallucinations, and emotional dysregulation, leading to psychosis.[6,7] Various studies have shown that the majority of inflammatory cells involved in RE are T-lymphocytes. These cells can lead to neuronal damage and inflammation within the affected hemisphere of the brain. These T-cells may recognize specific antigens within the brain tissue, triggering an immune response that results in cytotoxic effects on neurons, ultimately leading to neuronal death. These progressive brain tissue losses can be attributed to the various psychiatric manifestations in RE.[8,9] Additionally, the chronic and debilitating nature of RE, coupled with distressing symptoms such as progressive hemiplegia and cognitive decline, can exacerbate psychiatric distress. The combination of neuroinflammation, seizure activity, and structural brain changes leads to a range of psychiatric symptoms, including mood swings, aggression, psychosis, and cognitive impairment.

Psychiatric diagnostic and therapeutic challenges encountered in such cases include differentiating between primary psychiatric disorders and psychiatric symptoms secondary to RE. However, managing psychiatric symptoms poses a diagnostic dilemma as it remains unclear whether they directly result from seizure activity or exist independently. This ambiguity complicates treatment decisions, especially regarding the duration of antipsychotic therapy. Prolonged use of these drugs may concern the potential harmful side effects. Furthermore, administering steroids, while effective in treating RE-related inflammation, may exacerbate psychosis, further complicating treatment. Balancing seizure control and potential side effects of antiepileptic drugs is also challenging in optimizing patient care. The interdisciplinary collaboration between neurology, psychiatry, and rehabilitation services is essential for providing holistic care to individuals with RE. Pharmacological interventions targeting both seizures and psychiatric symptoms, alongside supportive therapies and psychosocial interventions, play a vital role in managing RE-related psychiatric manifestations.

CONCLUSION

RE presents a complex clinical picture with neurological and psychiatric manifestations. This case series highlights the importance of recognizing and managing psychiatric symptoms in RE. Early detection and interdisciplinary collaboration between neurology and psychiatry are crucial for comprehensive care. By addressing both neurological and psychiatric aspects, clinicians can improve outcomes and enhance the quality of life for patients with RE.

Ethics approval

The ethical approval was given by the ethics and scientific review committee Shyam Shah Medical College and Sanjay Gandhi Memorial Hospital, Rewa.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Author Contributions

All authors contributed significantly in the conceptualization, design, data collection, data analysis, manuscript preparation and review.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.