Unveiling post-COVID-19 Rasmussen’s encephalitis: a case report of rare neurological complication

Abstract

Introduction and importance:

Rasmussen encephalitis (RE) is a rare autoimmune disorder that causes unilateral inflammation of the cerebral cortex and can lead to drug-resistant epilepsy and progressive neurological decline. Although the emergence of RE following COVID-19 has not been well documented, it emphasizes the need to understand the impact of COVID-19 on neurological health. This case emphasizes the importance of early recognition and intervention to prevent adverse outcomes related to post-COVID-19 neurological complications.

Case presentation:

A 30-year-old woman, recently diagnosed with COVID-19, experienced recurrent seizures that primarily affected the left side of her body. Despite medical management, signs of progressive weakness and altered consciousness were observed. Neurological examination, imaging, and electroencephalography confirmed a diagnosis of post-COVID-19 RE. Despite conservative management, the patient’s condition continued to deteriorate, ultimately resulting in fatal outcomes.

Clinical discussion:

The relationship between COVID-19 and autoimmune responses, which can lead to neurological complications, such as RE, is a matter of concern. Accurate diagnosis of RE depends on imaging and EEG studies; however, a definitive diagnosis often requires histopathological examination. The management of RE involves the use of anti-seizure medications and surgical interventions to control symptoms and improve outcomes. However, the unusual presentation of this case, along with challenges in diagnosis and treatment, underscores the need for increased awareness and extensive research on the neurological consequences of COVID-19.

Conclusion:

This case underscores the severe neurological consequences that can emerge after COVID-19, emphasizing the need for prompt identification and intervention. Additional research is essential to improve the comprehension and management of the neurological aftermath of COVID-19 with the ultimate goal of enhancing patient outcomes.

Introduction

Highlights

• Rare neurological complication: The presentation of Rasmussen’s encephalitis following COVID-19 highlights the necessity of increased caution regarding post-viral neurological consequences.

• Diagnostic and management challenges: The presentation of a detailed case highlights the challenges in diagnosis and treatment, particularly for cases that are resistant to treatment, leading to the need for careful consideration of therapeutic strategies.

• Contribution to understanding: This study sheds light on the post-COVID-19 neurological complication known as RE by providing important information on its pathogenesis, diagnostic methods, and treatment options. The findings will be beneficial for future research and clinical practice in the field of neurological complications related to COVID-19.

RE is a disorder of the cerebral cortex that is characterized by inflammation of one side of the brain, drug-resistant epilepsy, and progressive deterioration of neurological and cognitive functions¹. Neuropathological and immunological studies have revealed that Rasmussen encephalitis is an immune-mediated disease with a predominant role in CD8+ T cytotoxic cells, microglial cells, and activation of the inflammasome pathway².

Rasmussen syndrome manifests as continuous partial seizures in three distinct stages of the disease process. The initial stage is a prodrome with sporadic hemiparesis crisis. The next stage begins with an increase in the frequency and severity of the hemiparetic crises and cognitive dysfunction. If it involves the dominant hemisphere, hemianopia and aphasia may occur. Finally, in the third phase, the frequency of sporadic hemiparetic crises decreases. However, permanent neurological deficits persist³. The occurrence of Rasmussen encephalitis following a recent COVID-19 infection is exceedingly rare, as evidenced by the lack of similar cases in existing literature. This case highlights the potential of COVID-19 to precipitate severe neurological complications, thereby necessitating a shift in focus toward comprehending its impact on the nervous system. Prompt reporting of this case constitutes a vital contribution to the scientific community, underscoring the need for extensive clinical research on COVID-19’s neurological sequelae. By documenting and disseminating such uncommon presentations, clinicians can enhance awareness, facilitate early recognition, and improve the management strategies for neurological complications associated with COVID-19. Ultimately, this can help to advance patient care and improve patient outcomes.

Case presentation

A 30-year-old woman newly diagnosed with COVID-19 arrived at the emergency department with repeated tonic-clonic seizures that predominantly affected the left side of her body over the past 12–14 h. She also experienced loss of consciousness, tongue biting, and episodes of falling. Subsequently, the patient developed partial weakness that gradually progressed to generalized weakness on the left side of the body.

Three weeks prior to her referral for neurological assessment, the patient presented to the outpatient department (OPD) with shortness of breath, mild fever, and cough. The patient had mild respiratory distress, but her oxygen saturation level was normal. Based on her symptoms, she was suspected of having COVID-19. Hence, we performed a reverse transcriptase-polymerase chain reaction (RT-PCR) to confirm this diagnosis. Owing to the absence of respiratory distress, we managed her COVID-19 infection conservatively. At this time, the patient did not exhibit any neurological symptoms. The patient was discharged after treatment for respiratory symptoms.

Upon the first assessment during the seizure episode, her heart rate was 114 beats per min, blood pressure was 100/65 mmHg, breathing rate was 22 breaths per min, and body temperature was 98F. Neurological examination revealed that the patient was oriented to the person only, with the Glasgow Coma Scale (GCS) score deteriorating from 12/15 to 8/15. Cranial nerves II–XII were intact. Motor examination showed normal muscle bulk, increased tone (hypertonia) in the left limbs, and moderate weakness (3/5) in the left limbs, with normal strength (5/5) in the right. Hyperreflexia was noted on the left side with an extensor plantar response (Babinski sign) and normal reflexes on the right side. Sensory examination revealed diminished light touch, pinprick, and vibration sensations on the left side and a normal sensation on the right side. Coordination and gait could not be assessed because of altered consciousness and weakness. Tongue biting and incontinence were noted during seizures. The remainder of this paper is organized as follows. There was no significant medical, surgical, or family history.

After resuscitation and stabilization of her condition, a comprehensive neurological examination was performed to assess the extent of altered consciousness and identify any focal neurological deficits. The patient also received intravenous midazolam, valproic acid, and carbamazepine to control seizures.

The diagnostic approach included a basic metabolic profile, a computed tomography scan without contrast, and a MRI scan. A spinal tap was also performed for cerebrospinal fluid analysis. The relevant laboratory investigations are summarized in Table 1.

Table 1.

Summary of the laboratory findings of the patient.

Parameters	Patient’s value	Results in normal range
CBC report
Hemoglobin (mg/dl)	8.4	12–14
Leukocytes (cells/microliter)	12 000	4000–11 000
Polymorphonuclear cells	84%	40–80%
Lymphocytes	10%	20–40%
Platelets (per microliter)	498 000	150 000–400 000
CSF report
Leukocytes (per mm3)	3	3–5
Glucose (mg/100 ml)	65	50–80
Protein (mg/ml)	80	15–60

CBC, complete blood count; CSF, cerebrospinal fluid.

MRI scan showed right cerebral atrophy with an ex-vacuo dilatation of the occipital horn of the right lateral ventricle along with adjacent gliotic changes and prominent CSF spaces likely sequelae of previous ischemic insult. No space-occupying lesions or midline shifts were observed (Fig. 1).

Figure 1.

MRI scan findings of the patient showing right cerebral atrophy with ex-vacuo dilation of the ipsilateral lateral ventricle.

Furthermore, electroencephalography (EEG) revealed generalized slow waves and intermittent theta waves (sharp waves), as illustrated in Fig. 2.

Figure 2.

Electroencephalography Findings of the patient showing generalized slow waves along with intermittent theta waves (sharp waves).

We continuously monitored the patient, including electroencephalogram (EEG) monitoring, to capture any ongoing epileptic activity and assess the seizure patterns.

On the basis of the patient’s clinical history, laboratory results, characteristic imaging findings, and recent history of COVID-19, she was diagnosed with post-COVID-19 Rasmussen encephalitis. Her EEG showed typical findings of Rasmussen encephalitis, confirming the diagnosis. During the hospital stay, she experienced recurrent episodes of seizures and did not respond to anti-seizure medication. Therefore, we recommended hemispherectomy. However, the patient’s medical power of attorney refused to undergo a hemispherectomy. She continued receiving medical management, but her condition continued to deteriorate, and she died on the 12^th day after her recent admission to the hospital.

Discussion

Theodore Rasmussen was a neurosurgeon who first described RE⁴. RE is an autoimmune disorder, and COVID-19 may trigger autoimmune responses, particularly in women, due to sex-specific factors. Severe inflammation and cytokine storms can lead to autoimmune reactivity against the nervous system, with immune cells potentially cross-reacting with the antigens in the central nervous system. Increased concentrations of pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-6, and IL-17 have the potential to stimulate self-reactive T and B cells to evade tolerance mechanisms. COVID-19 can potentially trigger autoimmune reactions, as immune cells activated by SARS-CoV-2 interact with antigens in the central nervous system (CNS)^5,6.

In the era of climate change, the COVID-19 pandemic caused by the zoonotic SARS-CoV-2 highlights the need for vigilance. Climate change significantly impacts the spread of infectious diseases by altering environmental conditions, such as temperature and rainfall patterns, necessitating enhanced disease monitoring and adaptable public health strategies. Additionally, human activities such as deforestation and urbanization increase contact with wildlife, raising the risk of disease transmission and complicating efforts to control zoonotic infections⁷.

It is worth mentioning that the RE spectrum is variable. Nunziata et al. ⁸ reported a case of a 6-month-old infant who presented with recurrent seizures, left conjugate eye deviation, and hypotonia. Our case involved a 30-year-old woman who presented with repeated tonic-clonic seizures that predominantly affected the left side, loss of consciousness, tongue biting, and falling episodes. Nunziata and colleagues observed focal neurological signs such as left conjugate eye deviation and hypotonia. In our case, the patient developed partial weakness that progressed to generalized weakness on the left side accompanied by hypertonia and hyperreflexia in her left limbs. In addition, Nunziata and colleagues reported cortical and subcortical hypodense areas in the left frontal and parietal lobes, indicating vasogenic edema and vascular inflammation on imaging studies. However, MRI in our case showed right cerebral atrophy with ex-vacuo dilation of the ipsilateral lateral ventricle without tumors or focal lesions. Regarding COVID-19 diagnosis and management, Nunziata and colleagues treated patients with antiviral and immunosuppressive therapies. In contrast, our case involved a woman diagnosed with mild respiratory symptoms who was managed conservatively. Nunziata and colleagues reported gradual clinical improvement and resolution of symptoms over weeks with combined therapy. In the present case, the patient’s symptoms did not improve after treatment.

The criteria for evaluating Rasmussen encephalitis, as outlined in the 2005 European consensus on its pathogenesis, diagnostic workup, and management, remain widely accepted by the academic community⁹. Diagnostic imaging techniques such as CT and MRI play a crucial role in diagnosing Rasmussen’s encephalitis. MRI scans typically reveal uni-hemispheric localized cortical atrophy, accompanied by at least one of the following characteristics⁹:

1. Increased intensity in gray or white matter in T2/FLAIR sequences.

2. Hyperintense signal or atrophy was observed in the head of the caudate on the same side and in the ex-vacuo dilatation of the ventricular system and sulci.

Furthermore, ex-vacuo dilatation can occur in patients with RE. However, further research is required to establish a clear causal relationship and understand the connection between brain tissue atrophy and compensatory ventricular enlargement. Notably, our patient fulfilled this criterion.

Cerebrospinal fluid (CSF) analysis may yield non-specific findings. The Montreal research group has documented the most extensive series of CSF examinations for Rasmussen encephalitis (RE). Approximately half of these examinations revealed normal cellular and protein levels. In the remaining cases, abnormal findings included elevated cell counts (ranging from 16 to 70 cells/µl, primarily lymphocytes), increased protein content (ranging from 50 to 100 mg/dl), or alterations in the colloidal gold curve with either an initial or mid-zone elevation. Only 15% of the abnormal CSF test results exhibited abnormalities in all three parameters. Oligoclonal bands displayed variability, ranging from absent to present in 0–67% of cases across the three smaller series⁹.

Interestingly, the following uni-hemispheric EEG findings strongly suggest RE.

• Alterations in background activity and sleep spindles.

• Localized deceleration of brainwave activity.

• Presence of multiple ictal discharges across various brain regions.

• Occurrence of subclinical ictal activity.

However, laboratory tests cannot be used to definitively diagnose Rasmussen-like encephalitis. Glutamate receptor (GluR3) antibodies in serum and CSF are not specific to RE and do not provide pathogenic clues for treatment selection. Histopathology plays a crucial role in diagnosis, with characteristic features, including cortical inflammation, neuronal loss, and gliosis confined to one cerebral hemisphere, typically progressive and multifocal. Other features, such as parenchymal macrophages, B cells, plasma cells, or viral inclusion bodies, can exclude the diagnosis of RE. Although RE is typically found in young children, our case of a patient in her 30s highlights its atypical presentation and diagnostic challenges³. This unusual age of onset, along with the COVID-19 infection and diagnostic challenges, underscores the uniqueness of our case. This highlights the need for increased awareness and thorough investigation of Rasmussen encephalitis across various age groups, leading to improved diagnostic and treatment approaches.

Advancements in mRNA vaccines have provided crucial insights into immune responses and neurological effects related to post-COVID-19 RE. The rapid development and deployment of mRNA vaccines, especially for COVID-19, highlight their adaptability and efficacy in managing infectious diseases and preventing severe outcomes¹⁰. These vaccines are pivotal in generating robust immune responses against SARS-CoV-2 and have demonstrated significant efficacy in preventing severe COVID-19. This is particularly relevant for neurological complications such as RE, as the strong immune response elicited by mRNA vaccines helps mitigate risks by controlling viral spread and reducing inflammation associated with severe infections.

Limitation

This case resulted in a fatal outcome and the patient died on the 12^th day of treatment. Therefore, we did not have a record of any health condition outcomes.

Conclusion

This case report highlights the severe neurological complications that can occur after COVID-19 infection, resulting in a fatal outcome in a young woman with a history of the disease. Rapid recognition and intervention are crucial for the effective management of neurological sequelae, emphasizing the need for heightened healthcare provider vigilance. Further research is required to understand and manage these complications better.

Ethical approval

Not applicable.

Consent

The publication of this case report and its accompanying images was authorized by obtaining written informed consent from the patient’s father. A copy of the consent form is readily available for review by editorial members of the journal, ensuring transparency and adherence to ethical standards regarding patient confidentiality and publication protocols.

Source of funding

Not applicable.

Author contribution

Z.N. and M.U.H. drafted the manuscript, and M.U.H., Z.N., and L.A. participated in the writing process. A.M.A. and Z.N. contributed to manuscript editing and actively engaged in patient care. All the authors have thoroughly reviewed and approved the final version of the manuscript.

Conflicts of interest disclosure

The authors declare no conflicts of interest.

Research registration unique identifying number (UIN)

Not applicable.

Guarantor

Muhammad Usman Hashmi.

Data availability statement

We declare data availability statement.

Provenance and peer review

Not commissioned, externally peer-reviewed.