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IDCases
IDCases
IDCases
2214-2509
Elsevier

S2214-2509(24)00140-9
10.1016/j.idcr.2024.e02064
e02064
Case Report
Progressive Multifocal Leukoencephalopathy confined to the posterior fossa as the presenting manifestation of HIV in a paediatric patient
Nshimiyimana JF. jules.nshimiyimana@akhskenya.org
⁎
Onsongo S.
Aga Khan Hospital, Kisumu, P.O. Box 530, Kisumu, Kenya
⁎ Corresponding author. jules.nshimiyimana@akhskenya.org
17 8 2024
2024
17 8 2024
37 e0206415 12 2023
16 8 2024
© 2024 Published by Elsevier Ltd.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Progressive Multifocal Leukoencephalopathy (PML), primarily affecting immunocompromised individuals due to the John Cunningham virus (JC), is common in HIV-positive adults but rare in paediatrics. We present a unique case of a 14-year-old female with PML as the initial manifestation of HIV, with MRI lesions isolated to the posterior fossa. Initial symptoms included fever and rash, progressing to neurological deficits and ataxia. Severe immune suppression due to HIV and JC virus in the cerebrospinal fluid were confirmed. Management included immune reconstitution therapy (antiretroviral treatment) and supportive care. Despite interventions, the patient had a slow recovery with significant residual neurological sequelae. Timely recognition of Immune Reconstitution Inflammatory Syndrome (IRIS) and steroid initiation proved helpful. Antiretroviral therapy improved the survival rate of HIV-related PML, but long-term neurological sequelae, especially in posterior fossa cases, significantly impact the patient's quality of life. This case highlights diagnostic and treatment challenges in paediatric PML, particularly with atypical lesions location.

Highlights

• Rare PML manifestation in pediatric HIV patients.

• Isolated Posterior fossa involvement in PML is uncommon.

• Challenges in diagnosing and treating PML in children.

Keywords

JC virus
Progressive Multifocal Leukoencephalopathy
Pediatric population
Immunocompromised patients
Posterior fossa lesions
Neurological deficits
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pmcIntroduction

Progressive Multifocal Leukoencephalopathy (PML) is a severe opportunistic disease caused by the JC virus. It typically affects individuals with compromised immune systems, such as those with human immunodeficiency virus (HIV), malignancies, autoimmune conditions, or undergoing immunosuppressive treatments. Cortese et al., [2]. The classic presentation of PML involves the subacute onset of neurological deficits in severely immunocompromised patients. In the paediatric population, PML is exceptionally rare [7] and can easily be overlooked when considering differential diagnoses for central nervous system (CNS) lesions [4]. We present a case of PML as the presenting manifestation of HIV infection, with lesions confined to the posterior fossa.

Case presentation

A 14-year-old Kenyan female initially presented at a local healthcare facility with a low-grade fever, diffuse skin rash, and developed a cough that had lasted for a few weeks. Over a three-week period, her symptoms worsened, leading to progressive ataxia and an inability to stand or walk without support. A brain CT scan at the local facility revealed non enhancing hypodense lesions in the cerebellum. The patient received a broad antibiotic cover for the then suspected cerebral abscesses, although there was little improvement in clinical status. Subsequent tests revealed a positive HIV test with severe immune suppression. Based on a positive urine LAM test for tuberculosis (TB) and suspicious findings on chest radiographs, central nervous system tuberculosis coverage was added to her regimen which already included antifungal medications in addition to intravenous antibiotics. Highly active antiretroviral therapy (HAART) was initiated before her discharge from hospital. The cause of her HIV infection was not clear from the history but suspected to be vertical transmission.

The patient was referred to our hospital about two months after discharge, with worsening unresponsiveness and restlessness. She had respiratory distress, requiring intubation in the intensive care unit (ICU). She had very little interaction with the environment and had non-purposeful eye opening. During her stay in the ICU, she had fevers, diarrhoea, and transient hypokalaemia. MRI of the brain revealed non-enhancing hypertense lesions involving the cerebellum, pons, and medulla (Fig. 1). Immune reconstitution inflammatory syndrome (IRIS) was suspected, leading to the initiation of intravenous dexamethasone, while antiretroviral therapy and anti-TB treatment were continued. Her CSF revealed normal cell count, normal glucose level of 4.88 mmol / L, a normal protein level of 36.16 mg/dL, negative cryptococcal Antigen and negative tuberculosis PCR in CSF. A positive cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for JC virus confirmed the diagnosis of probable Progressive Multifocal Leukoencephalopathy (PML). Testing for cytomegalovirus (CMV) in blood was negative. A chest CT scan had findings suggestive of pulmonary tuberculosis. Despite effective treatment of the above complications, she remained in a vegetative state for 7 weeks in the hospital.Fig. 1 MRI images demonstrating hyperintense lesions in the cerebellum and brainstem (A) and absence of white matter lesions over the supratentorial images (B).

Fig. 1

To support her care, a tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube for feeding were inserted. The patient was ultimately discharged for home-based care still in vegetative state. At three months of follow-up after discharge, she remained primarily bedridden, with at least some interactions with her mother such as showing where she feels pain etc. At seven months of follow up, the patient had recovered substantially with ability to feed orally, sit comfortably in a chair and follow up all commands. The tracheostomy was successfully closed and PEG tube was removed safely. However, she continued to experience spastic quadriparesis, more pronounced in the lower extremities (power 3/5) than the upper extremities (4 +/5).

Discussion

PML is a well-documented condition commonly observed in the adult population with HIV but also in several other immunosuppressed states. However, confinement of PML to the posterior fossa is rare, even in the adult population, and is primarily documented in the literature through case reports [8], [9]. A review of the literature focusing on PML cases with brainstem onset identified only nine cases, excluding those with cerebellar involvement [1]. In a study investigating the radiological and clinical manifestations of PML in patients treated with immunosuppressors, approximately 27.4 % of the cases had lesions localised in the posterior fossa [6]. However, it was not specified whether these lesions were isolated at the time of the disease. PML, being an AIDS-defining illness, is also rare as a presenting manifestation of HIV. The scarcity of this condition in the pediatric population may be attributed to the lower seroprevalence of JC virus in this age group. Seroprevalence rates are estimated to be around 16 % in children aged 1–5 years and 34 % in those aged 21–50 years. In contrast, the seroprevalence in adults is much higher, estimated at 86 % [10]. A literature search conducted in 2014 for PML cases in HIV-infected children identified only 19 cases, with the majority (12 patients) acquiring the infection through vertical transmission [10].

Most reported cases of PML in paediatric patients show MRI-detected lesions in supratentorial regions. The occurrence of Progressive Multifocal Leukoencephalopathy (PML) with lesions confined to the posterior fossa in HIV-infected children is exceptionally rare, particularly as the presenting symptom of HIV. Only a limited number of case reports have documented such occurrences in the medical literature [4], [5].

The unusual location of PML in the posterior fossa can lead to diagnostic and treatment uncertainties, as demonstrated in this case, which can ultimately impact the outcome. While immune reconstitution is the mainstay of PML treatment and directly affects the survival rate, prompt recognition of Immune Reconstitution Inflammatory Syndrome (IRIS) can be lifesaving, particularly in cases of suspected coinfection in the context of severe HIV infection. The administration of steroids has demonstrated beneficial effects, even in cases of HIV-related PML. However, the optimal dosage and duration of steroid therapy have yet to be established. Tan [11] In our case the possibility of IRIS related to pulmonary TB may have played a role in the prompt control of symptoms. IRIS can manifest early, within the first week, or after several weeks, as observed in our case, and in some instances, it can occur several months later [11].

The survival rate of HIV-related PML has significantly improved with the introduction of antiretroviral therapy, despite the absence of specific therapy targeting the JC virus itself. Among HIV-infected patients, approximately 50 % can survive PML, albeit with some experiencing significant neurological deficits. Falcó [3] However, on long-term follow-up (3 to 5 years), 66 % to 83 % of patients may show improvement or remain stable with regards to their neurological sequelae [2]. Notably, patients with cerebellar lesions tend to have more disabling outcomes on long-term follow-up due to ataxia and impaired coordination that affect their daily functioning. Cortese et al., [2].

Conclusion

This case highlights the diagnostic and treatment challenges associated with Progressive Multifocal Leukoencephalopathy (PML) in the pediatric population, particularly when the lesions are confined to the posterior fossa. PML, a severe opportunistic disease primarily affecting immunocompromised patients, is rarely observed as the presenting manifestation of HIV infection in children. Prompt recognition, accurate diagnosis, and appropriate management, including immune reconstitution therapy, are crucial for optimal outcomes. Despite the advancements in antiretroviral therapy, PML can still lead to significant neurological deficits. Long-term follow-up is essential, especially in cases involving cerebellar involvement, as neurological sequelae may significantly impact the patient's quality of life.

CRediT authorship contribution statement

Jules Fidele Nshimiyimana: Conceptualization, Data curation, Formal analysis, Writing – original draft, Writing-review-editing; Simon Onsongo: Writing – review & editing

Ethical approval

Not applicable.

Ethical considerations

Written informed consent was obtained from the patient for publication of this case.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Conflict of interest statement

All authors declare no conflict of interest.
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