Rasmussen’s encephalitis (RE) is a rare epilepsy syndrome associated with treatment-resistant seizures, cognitive decline and developmental sequelae.^1,2,3,4,5,6 Its incidence ranges between 1.7 and 2.4 per 10 million individuals.^2,3,6 Disease progression typically occurs in three clinical stages:⁶

Neuroimaging can detect pathological changes from 4 months after disease onset.⁷ Atypical forms of RE include adult-onset, bilateral RE and RE associated with other diseases.^1,8,9 Adult-onset RE may present as a ‘myoclonic phenotype’ (focal cortical myoclonus) or an ‘epileptic phenotype’ (focal motor seizures and more severe brain atrophy).¹

The pathogenesis of RE is poorly understood; however, it is postulated to be immune-mediated, involving both adaptive and innate immunity.^1,4,7 Hemispherectomy remains the only cure for resistant epilepsy, but carries risks of severe postoperative complications.^2,3,4 During early stages, immunotherapy may slow early progression, but does not prevent cognitive decline; evidence is limited to case series and lacks randomised controlled trials.^4,10

This case highlights severe cognitive decline in atypical RE and underscores the role of early neuroimaging in reducing morbidity.

Ethical clearance to conduct this study was obtained from the University of the Witwatersrand Human Research Ethics Committee (Ref. No. M241083). Written informed consent for publication was obtained from the patient’s legal guardian.

Mr X is a 34-year-old African male who was working as a security guard. He has no history of childhood seizures, head injury, substance use, metabolic disease, human immunodeficiency virus (HIV) or syphilis, and has no significant family history. He was diagnosed with epilepsy at age 24 years, following his first seizure; no neuroimaging was performed at the time. He subsequently developed frequent and severe generalised tonic-clonic seizures, which led to job loss and multiple hospital admissions. Subsequently, he developed a decline in cognitive functioning, including poor attention, memory, executive functioning and social cognition. Over the years, he received valproate, lamotrigine, risperidone, quetiapine and fluphenazine decanoate for epilepsy and behavioural disturbances. Despite medication adherence, he was readmitted several times as a result of uncontrolled seizures and behavioural problems. In 2014, his cognitive decline worsened, rendering him childlike and causing him to struggle with simple tasks, such that Mr X needed constant supervision in performing basic activities of daily living. In 2019, he developed transient hemiplegia, expressive aphasia and agraphia, along with disinhibited behaviour leading to recurrent hospitalisation. Over subsequent admissions, he exhibited severe disorganisation, poor self-care, hoarding behaviour and aggression; clozapine was trialled but discontinued because of seizure risk and poor response.

Mr X was transferred to Sterkfontein Hospital (SFH) because of ongoing problematic behaviour. At SFH, his medication included therapeutic dosages of amisulpride, sodium valproate, lamotrigine, orphenadrine and clothiapine (for sedation when necessary). Neurological examination revealed global aphasia with a positive grasp reflex. He had no cranial nerve fallout. His power was normal in all limbs, but reflexes were reduced. His sensation was decreased globally, and he had markedly reduced pain perception. There were no abnormalities detected on the cerebellum examination. Mental state examination indicated disorientation, incoherence and perseveration. His mood was euthymic with a reactive affect. Formal cognitive testing was limited by the severity of the impairment, with deficits evident in attention, executive function and language.

Mr X cannot fully participate in therapy because of cognitive impairment; however, psychology instituted a basic behavioural plan. Efforts to optimise the dose of amisulpride for behaviour control failed because of hyperprolactinaemia (55.20 µg/L), as did a trial of lithium. The lamotrigine dose was optimised to 150 mg twice a day. Despite initiating quetiapine and optimising to 400 mg twice daily, his behaviour remained unchanged. Fluoxetine was initiated, leading to improvement in impulsive and hoarding behaviour. His seizures remain well controlled on treatment.

Investigations done included a routine electroencephalogram (EEG) (10 August 2023), which was normal, blood and cerebrospinal fluid analysis, which showed no significant findings (Table 1). His Magnetic Resonance Imaging (MRI) brain (28 August 2023; Figure 1) displayed features consistent with RE of the left cerebral hemisphere, including cortical atrophy and ventricular dilation on a background of generalised brain atrophy. There was no evidence of ongoing inflammation, ischaemia or infarcts.

He was assessed as having Rasmussen encephalitis, currently in the residual phase, with major neurocognitive disorder probable due to RE, with behavioural problems.

Mr X’s prognosis is poor as a result of extensive cerebral atrophy and disease progression limiting treatment options.

Atypical RE is a rare variant of classic childhood-onset, unihemispheric form.¹ It includes adult-onset disease, bilateral involvement or association with other conditions.¹ These atypical features often delay diagnosis and limit treatment, as hemispherectomy is usually not feasible, leaving immunotherapy and supportive care as the main options.^2,3,4,10

The case presented demonstrates such one variant, in which delayed diagnosis contributed to loss of independence and functional decline, resulting in institutionalisation. Diagnosis is also challenging because of broad differentials, which can cloud the clinical picture. Further research is needed to clarify diagnostic pathways and treatment options, including well-designed randomised controlled trials.

Clinicians should consider atypical RE in individuals presenting with new-onset seizures and cognitive decline, especially in the context of comorbidities, older age and bilateral hemispheric involvement. Early detection and treatment may improve outcomes and reduce morbidity and mortality.