PICU Admission of Children for Status Epilepticus: Is There a Different Approach Between Referral and Second-Level Hospitals in an Italian Region?

Appropriate status epilepticus (SE) management is key to minimize admission to the pediatric intensive care unit (PICU). We retrospectively describe 115 children admitted to the PICU of the tertiary-care referral hospital of Padova for seizures, SE, and SE-related complications (59% from second-level hospitals, 41% from the referral hospital) and compare SE management among hospitals. Compared with the referral center, in second-level hospitals, anesthetics were more often administered as first/second drug (P < .001), and intubation was more frequent (P < .001). Intubation was significantly associated with SE onset at home (P = .045) and benzodiazepine-associated respiratory depression (P = .044). There was no association between intubation and SE duration, etiology, PICU length of stay, and morbidity at discharge. In conclusion, adherence to treatment protocols on SE management after the first-line drug differs between referral center and second-level hospitals. Lack of association with SE characteristics and patient's outcome suggests PICU admission could be due to inappropriate invasive management.

Electroclinical Features in Two Novel STRADA Patients and a Functional Yeast Assay for the Validation of Missense STRADA Mutations.

Loss of function of the STRADA gene, an upstream mTOR inhibitor, causes a rare neurodevelopmental disorder characterized by polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE syndrome). Patients display a homogeneous phenotype including early-onset drug-resistant epilepsy, severe psychomotor delay, multisystemic comorbidities, and increased risk of premature death. The administration of sirolimus, an mTOR inhibitor, is helpful in controlling seizures in this syndrome. We report the electroclinical phenotype of two novel patients and the development of a yeast model to validate the pathogenicity of missense variants. Patient 1 harbored a missense STRADA variant and had a peculiar electroclinical phenotype with a relatively mild epilepsy course. Patient 2 harbored a truncating STRADA variant and showed a typical PMSE phenotype and a favorable response to early treatment with sirolimus. When we modeled the p.(Ser264Arg) STRADA change in its yeast homolog SPS1, it impaired SPS1 function. The results underlie the importance of a timely molecular diagnosis in these patients and show that yeast is a simple yet effective model to validate the pathogenicity of missense variants.

Apneas requiring respiratory support in young infants with COVID-19: a case series and literature review.

The objective of this study is to describe the clinical features of young infants with apneas as a clinical sign of COVID-19. We reported the cases of 4 infants who needed respiratory support in our PICU for a severe course of COVID-19 complicated with recurrent apneas. Moreover, we conducted a review of the literature about COVID-19 and apneas in infants ≤ 2 months of corrected age. A total of 17 young infants were included. Overall, in most of the cases (88%), apnea was an initial symptom of COVID-19, and in two cases, it recurred after 3-4 weeks. Regarding neurological workup, most children underwent a cranial ultrasound, while a minority underwent electroencephalography registration, neuroimaging, and lumbar punctures. One child showed signs of encephalopathy on electroencephalogram, with further neurological workup resulting normal. SARS-CoV-2 was never found in the cerebrospinal fluid. Ten children required intensive care unit admission, with five of them needing intubation and three non-invasive ventilation. A less invasive respiratory support was sufficient for the remaining children. Eight children were treated with caffeine. All patients had a complete recovery.  Conclusion: Young infants with recurrent apneas during COVID-19 usually need respiratory support and undergo a wide clinical work-up. They usually show complete recovery even when admitted to the intensive care unit. Further studies are needed to better define diagnostic and therapeutic strategies for these patients. What is Known: • Although the course of COVID-19 in infants is usually mild, some of them may develop a more severe disease needing intensive care support. Apneas may be a clinical sign in COVID-19. What is New: • Infants with apneas during COVID-19 may require intensive care support, but they usually show a benign course of the disease and full recovery.

Myoclonic super-refractory status epilepticus with favourable evolution in a teenager with FIRES: Is the association of vagus nerve stimulation and cannabidiol effective?

BACKGROUND: Febrile infection-related epilepsy syndrome (FIRES) is a rare and catastrophic clinical syndrome occurring in previously healthy patients. Aetiology is still unknown and outcome usually poor. We describe a case of myoclonic prolonged super refractory status epilepticus (P-SRSE) in FIRES in a patient admitted to the paediatric intensive care unit of Padova, Italy. CASE REPORT: A previously healthy 14-year-old girl with onset of myoclonic status epilepticus after a mild febrile illness was admitted to our hospital with a diagnosis of FIRES. Extensive diagnostic work-up was inconclusive. Status epilepticus and electroclinical seizures recurred every time weaning from anaesthetic agents was attempted. Eventually, a vagal nerve stimulator (VNS) was implanted and cannabidiol (CBD) administered, 43 days and 70 days after P-SRSE onset, respectively. Two days after CBD introduction, status epilepticus weaned and the girl rapidly regained complete consciousness showing a brilliant and unexpected recovery. At last follow-up, 12 months later, she is 8-months seizure free on multiple antiseizure medications, has only mild neuropsychological impairment with no neurological and intellective deficit. CONCLUSIONS: To our knowledge, this represents a unique case with an extremely favourable evolution with a possible effect of the association of VNS and CBD to traditional antiseizure medications.

Functional Effects of Epilepsy Associated KCNT1 Mutations Suggest Pathogenesis via Aberrant Inhibitory Neuronal Activity.

KCNT1 (K+ channel subfamily T member 1) is a sodium-activated potassium channel highly expressed in the nervous system which regulates neuronal excitability by contributing to the resting membrane potential and hyperpolarisation following a train of action potentials. Gain of function mutations in the KCNT1 gene are the cause of neurological disorders associated with different forms of epilepsy. To gain insights into the underlying pathobiology we investigated the functional effects of 9 recently published KCNT1 mutations, 4 previously studied KCNT1 mutations, and one previously unpublished KCNT1 variant of unknown significance. We analysed the properties of KCNT1 potassium currents and attempted to find a correlation between the changes in KCNT1 characteristics due to the mutations and severity of the neurological disorder they cause. KCNT1 mutations identified in patients with epilepsy were introduced into the full length human KCNT1 cDNA using quick-change site-directed mutagenesis protocol. Electrophysiological properties of different KCNT1 constructs were investigated using a heterologous expression system (HEK293T cells) and patch clamping. All mutations studied, except T314A, increased the amplitude of KCNT1 currents, and some mutations shifted the voltage dependence of KCNT1 open probability, increasing the proportion of channels open at the resting membrane potential. The T314A mutation did not affect KCNT1 current amplitude but abolished its voltage dependence. We observed a positive correlation between the severity of the neurological disorder and the KCNT1 channel open probability at resting membrane potential. This suggests that gain of function KCNT1 mutations cause epilepsy by increasing resting potassium conductance and suppressing the activity of inhibitory neurons. A reduction in action potential firing in inhibitory neurons due to excessively high resting potassium conductance leads to disinhibition of neural circuits, hyperexcitability and seizures.

Corrigendum on: Ventilation weaning and extubation readiness in children in pediatric intensive care unit: A review.

[This corrects the article DOI: 10.3389/fped.2022.867739.].

Natural History Study of STXBP1-Developmental and Epileptic Encephalopathy Into Adulthood.

BACKGROUND AND OBJECTIVES: Pathogenic STXBP1 variants cause a severe early-onset developmental and epileptic encephalopathy (STXBP1-DEE). We aimed to investigate the natural history of STXBP1-DEE in adults focusing on seizure evolution, the presence of movement disorders, and the level of functional (in)dependence. METHODS: In this observational study, patients with a minimum age of 18 years carrying a (likely) pathogenic STXBP1 variant were recruited through medical genetics departments and epilepsy centers. Treating clinicians completed clinical questionnaires and performed semistructured video examinations while performing tasks from the (modified) Unified Parkinson Disease Rating Scale when possible. RESULTS: Thirty adult patients were included for summary statistics, with video recordings available for 19 patients. The median age at last follow-up was 24 years (range 18-58 years). All patients had epilepsy, with a median onset age of 3.5 months. At last follow-up, 80% of adults had treatment-resistant seizures despite long periods of seizure freedom in 37%. Tonic-clonic, focal, and tonic seizures were most frequent in adults. Epileptic spasms, an unusual feature beyond infancy, were present in 3 adults. All individuals had developmental impairment. Periods of regression were present in 59% and did not always correlate with flare-ups in seizure activity. Eighty-seven percent had severe or profound intellectual disability, 42% had autistic features, and 65% had significant behavioral problems. Video examinations showed gait disorders in all 12 patients able to walk, including postural abnormalities with external rotation of the feet, broad-based gait, and asymmetric posture/dystonia. Tremor, present in 56%, was predominantly of the intention/action type. Stereotypies were seen in 63%. Functional outcome concerning mobility was variable ranging from independent walking (50%) to wheelchair dependence (39%). Seventy-one percent of adults were nonverbal, and all were dependent on caregivers for most activities of daily living. DISCUSSION: STXBP1-DEE warrants continuous monitoring for seizures in adult life. Periods of regression are more frequent than previously established and can occur into adulthood. Movement disorders are often present and involve multiple systems. Although functional mobility is variable in adulthood, STXBP1-DEE frequently leads to severe cognitive impairments and a high level of functional dependence. Understanding the natural history of STXBP1-DEE is important for prognostication and will inform future therapeutic trials.

Trisomy 20p/monosomy 18p associated with congenital bilateral perisylvian syndrome.

We report the association, not previously described, between trisomy 20/ monosomy 18 and congenital bilateral perisylvian syndrome (CBPS), a condition featuring intellectual disability, epilepsy, oro-motor dysfunction and bilateral perisylvian polymicrogyria (BPP) in a 29-year-old individual. Detailed clinical evaluation, long-term EEG and EEG analysis by means of electrical source imaging (ESI), 3T MRI and array-CGH were performed. Clinical examination showed moderate/severe intellectual disability, dysmorphic features, oro-motor dysfunction, short stature, abnormal hands and feet, bradykinesia and abnormal posture. The patient had suffered from drug-resistant epilepsy since infancy. Brain MRI showed that BPP was consistent with CBPS. Additional imaging features revealed corpus callosum and cerebellar hypoplasia and fusion of the C1-C2 vertebrae. Ictal EEG and ESI documented tonic seizures originating from the right polymicrogyric cortex. Facial gestalt included dysmorphic features reported in patients with 18- and 20+ chromosomal rearrangements. Array-CGH showed an unbalanced translocation, arr(18p)x1(20p)x3. In conclusion, we provide a detailed electro-clinical and MRI description of a novel condition characterized by the association between trisomy 20p/monosomy 18p and CBPS, also illustrating its clinical evolution into adulthood. This information may help paediatricians, neurologists and geneticists to better counsel families about the developmental prognosis of this rare unbalanced chromosomal rearrangement.

Ventilation Weaning and Extubation Readiness in Children in Pediatric Intensive Care Unit: A Review.

Ventilation is one of the most common procedures in critically ill children admitted to the pediatric intensive care units (PICUs) and is associated with potential severe side effects. The longer the mechanical ventilation, the higher the risk of infections, mortality, morbidity and length of stay. Protocol-based approaches to ventilation weaning could have potential benefit in assisting the physicians in the weaning process but, in pediatrics, clear significant outcome difference related to their use has yet to be shown. Extubation failure occurs in up to 20% of patients in PICU with evidences demonstrating its occurrence related to a worse patient outcome including higher mortality. Various clinical approaches have been described to decide the best timing for extubation which can usually be achieved by performing a spontaneous breathing trial before the extubation. No clear evidence is available over which technique best predicts extubation failure. Within this review we summarize the current strategies of ventilation weaning and extubation readiness evaluation employed in the pediatric setting in order to provide an updated view on the topic to guide intensive care physicians in daily clinical practice. We performed a thorough literature search of main online scientific databases to identify principal studies evaluating different strategies of ventilation weaning and extubation readiness including pediatric patients receiving mechanical ventilation. Various strategies are available in the literature both for ventilation weaning and extubation readiness assessment with unclear clear data supporting the superiority of any approach over the others.

Efficacy of lacosamide in neonatal-onset super-refractory status epilepticus: a case report.

We report the case of a previously healthy newborn who developed super-refractory status epilepticus after Group B streptococcal meningoencephalitis. After administration of first-, second- and third-line anticonvulsants without resolution of status epilepticus, we started intravenous lacosamide as adjunctive therapy to phenobarbital, phenytoin and continuous infusion of ketamine and midazolam. After administration of lacosamide, we observed a clear-cut improvement in the neurological clinical condition coupled with seizure control on continuous video-EEG monitoring, even after suspension of all other medications except for phenobarbital. No adverse effects ascribable to lacosamide were reported. The available data regarding the use of lacosamide for status epilepticus in adults and children are promising, although there is as yet only anecdotal evidence for neonatal status epilepticus. Its lack of potential interactions, good tolerability and the option of intravenous use lend to its appeal as treatment for status epilepticus. To the best of our knowledge, this is one of the first reported cases of effective lacosamide infusion in neonatal-onset super-refractory status epilepticus. This evidence should prompt further investigation on efficacy and safety of lacosamide to support its use in this population.

SARS-CoV2 Related Multi System Inflammatory Syndrome in a Child with Chronic Kidney Disease: Case Report.

Since April 2020, several paediatric cases were reported with a multisystemic inflammatory syndrome related with SARS-CoV2, called MIS-C. In this case report, we describe a 2-year-old male with end-stage renal disease (ESRD) in renal replacement therapy (RRT) with peritoneal dialysis and severe hypertension affected by a severe SARS-CoV2 related illness characterised by multiorgan failure and need for intensive care, with clinical and instrumental features compatible with MIS-C. Most paediatric patients with kidney disease experience mild SARS-CoV2 disease and to our knowledge, this is the first case of a child with chronic kidney disease suffering from MIS-C. We believe that chronic kidney disease together with dialysis status and severe hypertension play a crucial role on developing severe forms of SARS-CoV2 related disease.

KCNT1-related epilepsies and epileptic encephalopathies: phenotypic and mutational spectrum.

Variants in KCNT1, encoding a sodium-gated potassium channel (subfamily T member 1), have been associated with a spectrum of epilepsies and neurodevelopmental disorders. These range from familial autosomal dominant or sporadic sleep-related hypermotor epilepsy to epilepsy of infancy with migrating focal seizures (EIMFS) and include developmental and epileptic encephalopathies. This study aims to provide a comprehensive overview of the phenotypic and genotypic spectrum of KCNT1 mutation-related epileptic disorders in 248 individuals, including 66 previously unpublished and 182 published cases, the largest cohort reported so far. Four phenotypic groups emerged from our analysis: (i) EIMFS (152 individuals, 33 previously unpublished); (ii) developmental and epileptic encephalopathies other than EIMFS (non-EIMFS developmental and epileptic encephalopathies) (37 individuals, 17 unpublished); (iii) autosomal dominant or sporadic sleep-related hypermotor epilepsy (53 patients, 14 unpublished); and (iv) other phenotypes (six individuals, two unpublished). In our cohort of 66 new cases, the most common phenotypic features were: (i) in EIMFS, heterogeneity of seizure types, including epileptic spasms, epilepsy improvement over time, no epilepsy-related deaths; (ii) in non-EIMFS developmental and epileptic encephalopathies, possible onset with West syndrome, occurrence of atypical absences, possible evolution to developmental and epileptic encephalopathies with sleep-related hypermotor epilepsy features; one case of sudden unexplained death in epilepsy; (iii) in autosomal dominant or sporadic sleep-related hypermotor epilepsy, we observed a high prevalence of drug-resistance, although seizure frequency improved with age in some individuals, appearance of cognitive regression after seizure onset in all patients, no reported severe psychiatric disorders, although behavioural/psychiatric comorbidities were reported in ∼50% of the patients, sudden unexplained death in epilepsy in one individual; and (iv) other phenotypes in individuals with mutation of KCNT1 included temporal lobe epilepsy, and epilepsy with tonic-clonic seizures and cognitive regression. Genotypic analysis of the whole cohort of 248 individuals showed only missense mutations and one inframe deletion in KCNT1. Although the KCNT1 mutations in affected individuals were seen to be distributed among the different domains of the KCNT1 protein, genotype-phenotype considerations showed many of the autosomal dominant or sporadic sleep-related hypermotor epilepsy-associated mutations to be clustered around the RCK2 domain in the C terminus, distal to the NADP domain. Mutations associated with EIMFS/non-EIMFS developmental and epileptic encephalopathies did not show a particular pattern of distribution in the KCNT1 protein. Recurrent KCNT1 mutations were seen to be associated with both severe and less severe phenotypes. Our study further defines and broadens the phenotypic and genotypic spectrums of KCNT1-related epileptic conditions and emphasizes the increasingly important role of this gene in the pathogenesis of early onset developmental and epileptic encephalopathies as well as of focal epilepsies, namely autosomal dominant or sporadic sleep-related hypermotor epilepsy.

Dexmedetomidine for EEG sedation in children with behavioral disorders.

OBJECTIVE: To evaluate the efficacy and safety of sedation with dexmedetomidine, a highly selective α2-agonist with sedative effect, for EEG recording in children with behavioral disorders. MATERIAL AND METHODS: Prospective observational study on children with behavioral disorders undergoing EEG at the Pediatric Hospital in Padova, Italy. A 2 mcg/kg intravenous bolus of dexmedetomidine was administered, followed by a 1-2 mcg/kg/h infusion. If necessary, bolus was repeated up to 3 times to reach the target level of sedation, assessed by Pediatric Sedation State Scale. Patients were fully monitored before, during and after the procedure until complete recovery. EEG recording quality, and caregivers' satisfaction were collected. Any adverse effect was registered using SIVA score. RESULTS: For this preliminary study, 19 patients were enrolled. EEG was successfully completed in all of them. Mean total dose of dexmedetomidine was 3.7 ± 1.7 mcg/kg. Adequate sedation was achieved within 11.9 ± 8 minutes. Mean time to first awakening was 30.9 ± 36.9 minutes and time to complete recovery 113.3 ± 92.7 minutes. Adverse effects (hypotension, bradycardia) were reported in 10 patients, all classified as "minor." EEG recording quality was good or excellent. Parents' satisfaction was high in all the interviewed families. CONCLUSIONS: Intravenous dexmedetomidine as a single drug showed an excellent efficacy and good safety profile for EEG recording in children with behavioral disorders.

Expanding the clinical and EEG spectrum of CNKSR2-related encephalopathy with status epilepticus during slow sleep (ESES).

OBJECTIVE: To investigate the clinical and EEG features of Encephalopathy with Status Epilepticus during slow Sleep (ESES) related to CNKSR2 pathogenic variants. METHODS: Detailed clinical history, repeated wakefulness/overnight sleep EEGs, brain MRI were collected in five patients, including one female, with CNKSR2-related ESES. RESULTS: Neurodevelopment in infancy was normal in two patients, delayed in three. Epilepsy onset (age range: 2-6 years) was associated with appearance or aggravation of cognitive impairment, language regression and/or behavioral disorders. Worsening of epilepsy and of cognitive/behavioral disturbances paralleled by enhancement of non-rapid eye movement (NREM) sleep-related, frontally predominant, EEG epileptic discharges [spike-wave-index (SWI): range 60-96%] was consistent with ESES. In three patients, episodes of absence status epilepticus or aggravation of atypical absences occurred, in this latter case associated with striking increment of awake SWI. Speech/oro-motor dyspraxia was diagnosed in four patients. In two patients, long-term follow-up showed epilepsy remission and persistence of mild/moderate cognitive disorders and behavioral disturbances into adulthood. CONCLUSIONS: Novel findings of our study are occurrence also in females, normal neurodevelopment before epilepsy onset, epilepsy aggravation associated with enhanced awake SWI, mild/moderate evolution in adulthood and language disorder due to speech/oro-motor dyspraxia. SIGNIFICANCE: Our findings expand the phenotypic spectrum of CNKSR2-related ESES.

Nontraumatic tension pneumopericardium in nonventilated pediatric patients: a review.

BACKGROUND AND AIMS: Pneumopericardium is a rare air leak syndrome caused by the abnormal presence of air in the pericardial sac, with a high risk of morbidity and mortality. It is clinically divided into nontension and tension pneumopericardium, with the latter resulting in a decreased cardiac output and circulatory failure. There are limited data regarding nontraumatic pneumopericardium in nonventilated pediatric patients. Therefore, we aimed to describe a case of tension pneumopericardium and review the available literature. METHODS: Case report and literature review of nontraumatic pneumopericardium in nonventilated pediatric patients. RESULTS: A 2-month-old infant developed cardiac tamponade secondary to tension pneumopericardium 11 days after cardiac surgery promptly resolved with pericardium drainage. We reviewed the literature on this topic and retrieved 50 cases, of which 72% were nontension whereas a minority were tension pneumopericardium (28%). Patients with tension pneumopericardium were mostly neonates (35.7% vs 22.2%), presented with an isolated air leak (64.3% vs 36.1%), and had a history of surgery (28.6% vs 8.3%) or hematological disease (28.6% vs 11.1%). In all nontension cases, treatment was conservative, whilst in all other cases, pericardiocentesis/pericardium drainage was carried out. There was a high survival rate (86.0%), which was lower in patients with tension pneumopericardium (71.4% vs 91.6%). CONCLUSIONS: Pneumopericardium is a rare condition with a higher mortality rate in patients with tension pneumopericardium, which requires immediate diagnosis and treatment. In nonventilated patients, tension pneumopericardium occurred more frequently in neonates, as an isolated air leak, and in those with a history of surgery or hematological disease.

Brain malformations associated to Aldh7a1 gene mutations: Report of a novel homozygous mutation and literature review.

BACKGROUND: The ALDH7A1 gene is known to be responsible for autosomal recessive pyridoxine-dependent epilepsy (OMIM 266100). The phenotypic spectrum of ALDH7A1 mutations is very heterogeneous ranging from refractory epilepsy and neurodevelopmental delay, to multisystem neonatal disorder. AIM: The present study aims at describing the phenotype associated with a novel homozygous ALDH7A1 mutation and the spectrum of brain malformations associated with pyridoxine-dependent epilepsy. METHODS: We conducted a literature review on the Internet database Pubmed (up to November 2017) searching for ALDH7A1 mutations associated with brain malformations and brain MRI findings. RESULTS: We present the case of two siblings, children of related parents. The proband presented neonatal focal seizures not responding to conventional antiepileptic drugs. Electroencephalography showed a suppression burst pattern and several multifocal ictal patterns, responsive to pyridoxine. Brain MRI was normal. Molecular analysis by targeted next-generation sequencing panel for epileptic encephalopathy disclosed a homozygous missense mutation of ALDH7A1. The same mutation was then found in a stored sample of DNA from peripheral blood of an older sister dead 3 years earlier. This girl presented a complex brain malformation diagnosed with a foetal MRI and had neonatal refractory seizures with suppression burst pattern. She died at 6 months of age. LITERATURE REVIEW: The brain abnormalities most frequently reported in pyridoxine-dependent epilepsy include: agenesia/hypoplasia of the corpus callosum, not specific white matter abnormalities, large cisterna magna, ventriculomegaly, haemorrhages, cerebellum hypoplasia/dysplasia, and, more rarely, dysplasia of the brainstem and hydrocephalus. DISCUSSION AND CONCLUSIONS: ALDH7A1 mutations have been associated to different brain abnormalities, documented by MRI only in few cases. The study cases expand the clinical spectrum of ALDH7A1 associated conditions, suggesting to look for ALDH7A1 mutations not only in classical phenotypes but also in patients with brain malformations, mainly if there is a response to a pyridoxine trial.

Directional Reaching for Water as a Cortex-Dependent Behavioral Framework for Mice.

Optogenetic tools and imaging methods for recording and manipulating brain activity have boosted the field of neuroscience in unprecedented ways. However, behavioral paradigms for mice lag behind those of primates, limiting the full potential of such tools. Here, we present an innovative behavioral framework in which head-fixed mice directionally reach for water droplets, similar to the primate "center-out" reaching task. Mice rapidly engaged in the task, performed hundreds of trials, and reached in multiple directions when droplets were presented at different locations. Surprisingly, mice used chemosensation to determine the presence of water droplets. Optogenetic inactivation of the motor cortex halted the initiation and rapidly diverted the trajectory of ongoing movements. Layer 2/3 two-photon imaging revealed robust direction selectivity in most reach-related neurons. Finally, mice performed directional reaching instructed by vibratotactile stimuli, demonstrating the potential of this framework for studying, in addition to motor control, sensory processing, and decision making.

Safety and immunogenicity of a quadrivalent human papillomavirus vaccine in HIV-infected and HIV-negative adolescents and young adults.

Human papillomavirus (HPV) infection is highly prevalent and can lead to cancer; the development of safe and efficacious vaccines for HPV is a major public health concern. The two licensed HPV vaccines contain recombinant virus-like particles of HPV 16 and 18; one of such vaccines also protects against HPV types 6 and 11 which cause genital warts. We determined safety and immunogenicity of quadrivalent HPV vaccine in HIV-infected and HIV-negative adolescents and young adults, aged 13-27 years. The seroconversion rate, assessed by antibody titers, 1 month after the administration of the third vaccine dose was 0.85 (95% CI 0.75-0.95) in the HIV-infected group and 0.91 (0.83-0.99) in the HIV-negative subjects (p=0.52). The vaccine was generally safe and well tolerated; the most common side effect was local pain and the most frequent systemic side effect was headache. This is the first report on response to HPV vaccination in both female and male HIV-infected adolescents and young adults and highlights that this population may benefit from HPV immunoprophylaxis. Further studies are needed to examine the long term efficacy of this vaccine in HIV-infected individuals.