We report a case of a perinatally HIV-infected patient aged 9 years, who presented with right-sided hemiplegia. His initial CD4 T-cell was of 0.21% (4 cells/
Progressive multifocal leukoencephalopathy (PML) is caused by the JC virus (JCV). As a demyelinating disease, PML typically presents with altered mental status, motor deficits, and ataxia, and is associated with immunosuppression, especially human immunodeficiency virus (HIV) [
A previously healthy 9-year-old boy (whose mother was recently found to be HIV-positive) presented to the hospital with 1 week of right-sided hemiplegia and right-sided facial palsy. Past medical history included psoriasis, diagnosed 4 years prior. His only HIV exposure was perinatal. On exam the patient weighed 22 kilograms, and vitals signs were within normal limits. He was alert and oriented with a normal level of consciousness and responded appropriately to questions. His speech was slowed and slurred, but this was his baseline according to his mother. He had right-sided facial palsy and right-sided tongue deviation; otherwise cranial nerves were intact. The boy had 3/5 strength in the right upper extremity and 4/5 strength in the right lower extremity. Left-sided strength was 5/5. The patient was able to walk with limited difficulty. Deep tendon reflexes were 2+ and 3+ throughout. Babinski’s sign showed dorsiflexion of the right 1st toe. Sensation was intact throughout. The patient also had clusters of 1-2 mm skin colored papules on his forehead and left cheek in addition to diffuse mild psoriatic scaling. Immunizations were up to date. The patient was admitted for a workup of these symptoms.
Laboratory studies showed complete blood count: hematocrit 31.6%, hemoglobin 10.5 g/dL, white blood cell count 5000 cells/
Three days after admission a brain computerized tomography (CT) scan was performed and showed frond-like hypodense lesion at the left frontal lobe with mild effacement of the left frontal horn of the lateral ventricle. Highly active antiretroviral therapy (HAART) regimen was subsequently started 10 days after admission, consisting of GPOvir-Z (coformulated zidovudine 250 mg, lamivudine 150 mg, and nevirapine 200 mg) [
CT on day 30 of onset of symptoms and 1 week post-HAART initiation.
MRI on day 38 of onset of symptoms and 2 weeks post-HAART initiation.
The patient was discharged 7 weeks after the first admission. Upon discharge he was able to walk with assistance, but was unable to speak.
The patient was readmitted one day after discharge due to autonomic nervous system dysfunction (nausea, vomiting, and loss of bowel and bladder tone). Deep tendon reflexes were 4+ throughout, and Babinski was positive bilaterally. Continued improvement of immunologic (CD4 T-cell count 2.0%, 30 cells/
2nd MRI, 3 1/2 months after onset of symptoms, 3 days post-HAART cessation.
The patient was readmitted 1 month later (100 days after onset of symptoms). Immune Reconstitution Inflammatory Syndrome (IRIS) was suspected, and the boy was treated with methylprednisolone (2 mg/kg/day) for 5 days. Despite HAART suspension and administration of steroids, his clinical symptoms worsened. The third MRI (Figure
3rd MRI, 4 months after onset of symptoms, 19 days post-HAART cessation.
Clinical manifestations and plasma HIV RNA and CD4 cell count levels.
We report the 2nd case of IRIS associated PML in a perinatally HIV-infected child. Since 1992 there have been reports of 14 HIV-infected children having PML (Table
Overview of studies concerning progressive multifocal leukoencephalopathy in HIV-infected children.
Author | Year reported | Sex | Age (years) | Country | Presentation | MRI/CT | Previous HIV- related event | HAART regimen | CD4 T-cell % or count (cell/ | Viral load (copies/mL) | Outcome | ||
Baseline | Nearest to episode | Baseline | Nearest to episode | ||||||||||
Oberdorfer et al. | 2009 | M | 9 | Thailand | Right hemiplegia | Frond-like hypodense lesion at the left frontal lobe | None | Initially nothing then AZT, 3TC, NVP | 0.21 | 0.21 | 185 976 | 185 976 | Dead |
Liptai et al. | 2007 | M | 15 1/2 | Hungary | Dizzy, diplopia, clumsy right hand, unsteady gait | Large, nonenhancing lesion of the right cerebellar heimsphere with a slight mass effect | None reported | Initially AZT, ddl then refused HAART | 37 | 10.5 | 2900 | 256 000 | Dead |
Shah and Chudgar. | 2005 | F | 8 1/2 | India | Right-sided dystonia, inability to talk, eat, or sit | Asymmetrical subcortical, right frontoparietal, left occipitoparietal and left vasal ganglia lesions | Generalized tonic clonic seizures and loss of consciousness | Initially nothing then AZT, 3TC, EFV, NLF | 320 | Alive, still has dystonia | |||
Robinson et al. | 2004 | M | 17 | USA | Dysarthric speech, facial palsy | Multiple confluent areas of high signal and fluid attenuated inversion recovery in the corona radiata bilaterally | Pneumocystis jiroveci pneumonia | Initially AZT, 3TC then d4T, NVP, lopinavir/ ritonavir then included cidofovir | 3 | 3 | 10–90 000 | 29 100 | Stable, wide-based gait, dysarthria, right-sided tongue deviation |
Nuttall et al. | 2004 | M | 12 | South Africa | Acute cerebellar dysfunction, hemiparesis | Nonenhancing low density lesion in the left cerebellar hemisphere | Growth failure, chronic lung disease | d4T, 3TC, efavirenz | 1.08 | 5.45 | 96 000 | Undetectable | Stable, mild cerebellar dysfunction |
Inui et al. | 1999 | M | 12 | Jaban | Left upper extremity weakness | White matter lesions of the right frontal, parietal and occipital lobes | Candida stomatitis | AZT then ritonavir and 3TC added | 9.5 | 7600 | Stable, left hemiparesis | ||
Araujo et al. | 1997 | M | 10 | Brazil | Subacute cerebellar dysfunction, dementia | Focal nonenhancing area of low attenuation in the cerebellum | None reported | ||||||
Morriss et al. | 1997 | M | 7 | USA | Decreased activity, slurred speech, ataxia | Confluent, nonenhancing, low density lesion in the right cerebellar white matter, middle cerebellar peduncle and dorsolateral pons | Candida esophagitis | ddc | 0 | Death | |||
Whiteman et al. | 1993 | M | 10 | USA | |||||||||
F | 12 | USA | Increased signal intensity in the basal ganglia and corona radiata bilaterally | ||||||||||
Berger et al. | 1992 | F | 13 | USA | Dysarthria, paresthesias of tongue and chin | Sinusitis and hyperintense signals in the basal ganglia | Oral candidiasis | AZT | 421 | 7 | Death | ||
M | 10 | USA | Facial palsy | Left frontal lobe lesion | Pneumocystis jiroveci pneumonia | AZT | 100 | Death | |||||
Vandersteenhoven et al. | 1992 | M | 7 | USA | Decreased activity, left hemiparesis, falling | Bilateral confluent abnormal white matter hyperintensity in the region of the right subcortical/ periventricular region | None reported | Initially nothing then AZT | 390 | Death |
Neuroimaging is an important part of the diagnosis. Multiple bilateral areas of white matter demyelination without contrast enhancement or mass effect are typical findings. For CT imaging these appear hypodense, while on MRI they have either decreased or increased signals depending on the imaging parameters [
Although rare, casesof PML associated with IRIS occur where there is clinical deteriorationdespite improvement of immunological and virologicalmeasures after the initiation of HAART [
PML in HIV-infected adolescents has a wide distribution of ages and geography. Despite the cases presented here, there is limited information about this disease in children. Underdiagnosis is likely to both perpetuate this knowledge gap and discourage physicians from identifying this condition. Additionally, in developing countries, such as Thailand, lack of imaging and laboratory data may further hinder diagnosis. Clinicians should then be cognizant of both of this condition and sequelae after HAART, so that prompt diagnosis and treatment can be made. Clear guidelines would be beneficial to clinicians who face these complex patients.
Lamivudine;
Ziduvodine;
Stavudine;
Zalcitabine;
Didanosine;
Efavirenz;
Highly active antiretroviral therapy;
Nelfinavir;
Nevirapine.
The authors would like to thank Dr. Virat Sirisanthana who provided valuable advice. This work was supported by Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand (to P. Oberdorfer, K. Katanyuwong, and P. Jpttamala) and by a grant from the NIH/Fogarty Clinical Research Training Scholars Program (to C.H. Washington).