Introduction

The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in a significant global health crisis, affecting millions of individuals worldwide. While the respiratory manifestations of COVID-19 have been well documented, the potential of the virus to cause systemic and long-term complications has become increasingly evident. It was noted that more than 90% of COVID-19 patients have reported experiencing at least one subjective neurological symptom, emphasizing the significance of the potential neurological effects of the disease [1]. The general, non-specific neurological symptoms frequently observed in COVID-19 patients include headache, confusion, and dizziness [2]. In contrast, the pediatric population commonly experiences symptoms such as headaches, seizures, encephalopathy, and muscle weakness [3]. Acute necrotizing encephalopathy (ANE) was first described in 1995 as a complication of viral respiratory tract infection in pediatric patients, with RNA viruses implicated in most cases [4, 5]. It is characterized by the presence of symmetrical multifocal lesions with predominantly thalamic involvement, as well as the involvement of the brainstem, white matter of the brain, and cerebellum [6]. The tomography images reveal lesions with lower density compared to the gray matter, whereas MRI scans demonstrate a low-intensity signal in T1, a high-intensity signal in T2, and FLAIR sequences, along with internal hemorrhage and restricted regions involved. Furthermore, ring enhancement is observed after gadolinium administration [7, 8].

Case Presentation

This case involves a 26-year-old male patient who presented with generalized weakness and headaches for one week. He subsequently tested positive for SARS-CoV-2. At the time of diagnosis, the only available vaccine was Sputnik V, which the patient decided to receive following his infection with SARS-CoV-2. Ten days later, he received the Sputnik V vaccine, which caused an unusual euphoric state that was not typical for him. Two days following this vaccine, the patient’s relatives reported that he was feeling weak and lacked energy. The patient has a medical history of right cerebellar anaplastic medulloblastoma and has undergone 28 sessions of radiotherapy and 4 sessions of chemotherapy with cisplatin and etoposide, as well as two surgical interventions. As a result, the patient has had a known history of dysarthria and stable left cerebellar syndrome for the past six years.

Two months later, the condition had worsened, with increased dysarthria and difficulty walking, a cerebellar ataxic gait to the left, as well as tension-type headaches of variable intensity reaching 10/10 on the VAS scale without associated nausea or vomiting. With no improvement in their symptoms, they went to a private doctor, who requested a computerized axial tomography of the skull (Fig. 1). The scan revealed a hypodense lesion in the right thalamus, with a hyperdense border and punctiform hemorrhage. The lesion extended to the posterior arm of the internal capsule and measured 4.3 × 3.5 × 2.2 cm in its three axes. This lesion was compressing the interventricular foramen and third ventricle, resulting in increased lateral ventricle amplitude; in addition, there were post-surgical changes present following a medial occipital craniectomy, with an area of gliosis in the dorsal and rostral regions of the paravermian areas.

Fig. 1
figure 1

Axial tomography in simple phase. Diagnosis of COVID-19-related hemorrhagic encephalitis

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During the evaluation at the emergency department one week later, the patient was found to be awake, alert, and able to maintain attention for extended periods. However, the patient still presented with mixed dysarthria, which was characterized by being flaccid and hypokinetic. The examination of the cranial nerves did not reveal any alterations. Motor exploration revealed hyperreflexia and a left patellar clonus. Gait was supported, but with an expanded support base and instability when standing in multiple directions. In addition to ataxia, limb dysmetria was seen in the upper limbs when performing the nose-finger test, with left-sided predominance. Generalized dysdiadochokinesia and dyssynergia of the four extremities were observed when performing the overshooting and Steward-Holmes maneuvers.

A cerebrospinal fluid analysis was performed, which revealed only a small number of reactive and mature lymphocytes, with no evidence of microorganisms or neoplastic cells present in the sample. Magnetic resonance imaging of the skull (Fig. 2) showed the presence of multiple hemorrhagic lesions with surrounding edema in the right thalamus. These lesions extended to the posterior arm of the internal capsule, while a smaller hemorrhagic lesion was also noted in the left thalamus. Additionally, there was another lesion that had expanded to the ipsilateral peduncle. All sequences showed heterogeneous hypointense behavior, indicating chronic bleeding coupled with the presence of perilesional edema; compared to the last image control, there was no hemorrhagic lesion or malformation that could suggest any radio-induced malformation; it did not show implants or tumor lesions dissemination in the medulla, spectroscopy with a filter to assess taurine negative for progression of medulloblastoma and cerebrospinal fluid without neoplastic cells evaluated in pathology.

Fig. 2
figure 2

Axial magnetic resonance imaging, sequences T1 (a, b), T2 (c, d), FLAIR (e, f), DWI (g, h), SWI (i, j), and T1 with gadolinium (k, l). A diagnosis of COVID-related hemorrhagic encephalitis was made based on the presence of multiple hyperintense lesions in the subcortical white matter, basal ganglia, thalamus, brainstem, and cerebellum in T2, FLAIR, and DWI sequences, with restricted diffusion in DWI and blooming in SWI

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Following the analysis of imaging studies and a positive PCR test for SARS-CoV-2 in the cerebrospinal fluid, a diagnosis of post-COVID hemorrhagic encephalitis was established. Treatment with methylprednisolone boluses was initiated, and the patient showed signs of improvement.

The relatives of the patient first opted to discharge him so he could undergo private therapy. They eventually changed their minds and brought him back to our facility, where he was readmitted. Despite receiving plasmapheresis five times, there was no discernible clinical improvement in his condition. Additionally, the existence of supratentorial hydrocephalus exacerbated his degree of consciousness. As a result, it was decided to place a ventriculoperitoneal shunt to address the condition.

An imaging study (Fig. 3) confirmed a lung infection due to poor secretion management. Broad-spectrum antibiotic treatment was initiated, along with mechanical ventilation and management with amines to address circulatory compromise. The patient’s condition improved satisfactorily after seven days, and this treatment was discontinued. For discharge, on the neurological evaluation, the patient was found to be awake with spontaneous eye opening but unable to follow commands or speak; campimetry did not reveal any abnormalities, a general decrease in strength; in addition to generalized hypertonia and hyperreflexia, bilateral clonus was also present, along with Hoffman and Trommer reflexes. Slight nuchal rigidity was also noted, a gastrostomy probe was placed, and control magnetic resonance imaging with follow-up in an outpatient consult was requested for monitoring of both the medulloblastoma and the hemorrhagic encephalitis processes.

Fig. 3
figure 3

Simple chest-computed tomography. A diagnosis of lung infection due to poor management of secretion

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Discussion

In the literature, multiple reports of neurologic involvement in patients, primarily adults, with coronavirus disease have been reported; these include encephalopathy, seizure, meningitis, and stroke [4]. The cases of acute necrotizing encephalopathy have been reported in severe COVID-19 infection in adults and one in the pediatric population [6]. The hallmark of ANE is multiple necrotic brain lesions showing symmetric distribution [9].

This case report highlights the importance of considering neurological complications in patients with an antecedent of COVID-19 infection, especially those with severe and atypical symptoms. Magnetic resonance imaging is considered the study of choice for SARS-CoV-2-related neurological damage. Characteristic imaging features include symmetrical multifocal lesions, predominantly in the thalamus, brainstem, brain white matter, and cerebellum. These lesions are hypodense on tomography images and hyperintense on T2/FLAIR, with areas of internal bleeding. Magnetic susceptibility sequences such as T2 or SWI, after administration with gadolinium, may show variable enhancement patterns, such as dotted, linear, annular, or incomplete annular. Although this is a single case in an adult patient, we cannot establish causality or generalizability.

Seizures were frequently present, and the prognosis was often poor neurologic involvement in a term neonate with prenatal exposure to SARS-CoV-2 was described for the first time in 2022; the brain in the MRI documented scattered foci of altered signal together with hemorrhagic foci; therapy based on antibiotics, antivirals, and antiepileptic drugs failed; following the research; several autoantibodies such as anti-myelin oligodendrocyte glycoprotein (MOG) antibodies were detected [10]. In adults with COVID-19 with the initial presentation with neurological and respiratory symptoms, most cases manifested respiratory symptoms as an early manifestation of SARS-CoV-2 infection; several cases developed neurological impairment following respiratory symptoms; the latency between the onset of the infection with respiratory manifestations and the onset of neurological complications varied between 3 and 41 days.

Some cases were marked by the identification of specific neuronal antibodies; three patients suffered from NMDA encephalitis, and their clinical manifestations were psychotic symptoms and seizures only; all of them improved with immuno-therapies including IV methylprednisolone and therapeutic plasma exchange; other cases developed MOG antibody-associated encephalitis and had minor clinical manifestations, but multiple MRI signal alterations in T2 and FLAIR sequences [11], mainly with cortical distribution; this ratio improved after IV steroid, and their main manifestation was truncal cerebellar dysfunction [12].

SARS-CoV-2 can cause neurological damage through various mechanisms, such as direct damage to specific receptors, cytokine-associated lesions, retrograde progression through nerve fibers, and secondary hypoxia. When SARS-CoV-2 binds to the pulmonary epithelium, a systemic inflammatory response involving interleukins such as IL-6, IL-12, IL-15, and TNF-a is generated, which activates glial cells and produces a massive pro-inflammatory state, leading to alterations in the nervous system [13].

Acute necrotizing encephalopathy after SARS-CoV-2 infection has been described in a few cases but should not be neglected in the differential diagnosis of neurological complications in patients with radiological image alterations, as evidence suggests that patients recovered from a severe COVID-19 picture may present a cytokine storm syndrome [14, 15].

Furthermore, it is also important to note that SARS-CoV-2-related neurological complications are not limited to the acute phase of the illness. Some studies have reported that patients who have recovered from COVID-19 may continue to experience neurological symptoms such as cognitive impairment, fatigue, and headaches for an extended period, which is referred to as the post-acute sequelae of the SARS-CoV-2 infection.

Conclusion

Acute necrotizing encephalopathy presents a great clinical and diagnostic challenge, close clinical and radiological follow-up is essential, and magnetic susceptibility sequences (T2 or SWI) should be included in the diagnosis protocol. Early recognition and intervention are key to preventing mortality and improving patient outcomes. As only a few cases reported in children are currently available, a more detailed description of the treatment and findings is necessary to prevent patient mortality.