Acquired auditory agnosia in childhood and normal sleep electroencephalography subsequently diagnosed as Landau-Kleffner syndrome: a report of three cases.

Aim  We report three cases of Landau-Kleffner syndrome (LKS) in children (two females, one male) in whom diagnosis was delayed because the sleep electroencephalography (EEG) was initially normal. Method  Case histories including EEG, positron emission tomography findings, and long-term outcome were reviewed. Results  Auditory agnosia occurred between the age of 2 years and 3 years 6 months, after a period of normal language development. Initial awake and sleep EEG, recorded weeks to months after the onset of language regression, during a nap period in two cases and during a full night of sleep in the third case, was normal. Repeat EEG between 2 months and 2 years later showed epileptiform discharges during wakefulness and strongly activated by sleep, with a pattern of continuous spike-waves during slow-wave sleep in two patients. Patients were diagnosed with LKS and treated with various antiepileptic regimens, including corticosteroids. One patient in whom EEG became normal on hydrocortisone is making significant recovery. The other two patients did not exhibit a sustained response to treatment and remained severely impaired. Interpretation  Sleep EEG may be normal in the early phase of acquired auditory agnosia. EEG should be repeated frequently in individuals in whom a firm clinical diagnosis is made to facilitate early treatment.

Reversible acquired epileptic frontal syndrome and CSWS suppression in a child with congenital hemiparesis treated by hemispherotomy

Rapport de synthèse : Cette thèse a étudié en détail le cas d'un enfant souffrant d'une hémiplégie congénitale sur un infarctus prénatal étendu qui a développé une forme particulière d'épilepsie, le syndrome des pointes ondes continues du sommeil (POCS), associé à une régression mentale massive. Les caractéristiques de cette détérioration pointaient vers un dysfonctionnement de type frontal. Une chirurgie de l'épilepsie (hémisphérotomie) a, non seulement, permis la guérison de l'épilepsie mais une récupération rapide sur le plan comportemental et cognitif, suivie d'une reprise plus lente du développement, avec finalement à l'âge de 11 ans un niveau de déficience intellectuelle modérée. L'intérêt de cette étude réside dans le fait que l'enfant a pu être suivi prospectivement entre l'âge de 4.5 ans et 11 ans par des enregistrements électro-encéphalographiques (EEG) ainsi que des tests neuropsychologiques et des questionnaires de comportements sériés, permettant de comparer les périodes pré-, péri- et postopératoires, ce qui est rarement réalisable. Un enregistrement EEG de surface a même pu être effectué durant l'opération sur l'hémisphère non lésé, permettant de documenter l'arrêt des décharges épileptiformes généralisées dès la fin de l'intervention. L'hypothèse que nous avons- souhaité démontrer est que la régression comportementale et cognitive présentée par l'enfant après une période de développement précoce presque normale (retard de langage) était de nature épileptique : nous l'expliquons par la propagation de l'activité électrique anormale à partir de la lésion de l'hémisphère gauche vers les régions préservées, en particulier frontales bilatérales. L'hémisphérotomie a permis une récupération rapide en déconnectant l'hémisphère gauche lésé et épileptogène de l'hémisphère sain, qui a ainsi pu reprendre les fonctions cognitives les plus importantes. Les progrès plus lents par la suite et l'absence de rattrapage au delà d'un niveau de déficience mentale modérée sont plus difficiles à expliquer: on postule ici un effet de l'épilepsie sur le développement de réseaux neuronaux de l'hémisphère initialement non lésé, réseaux qui sont à la fois à un stade précoce de leur maturation et en cours de réorganisation suite à la lésion prénatale. La littérature sur les déficits cognitifs avant et après hemisphérotomie s'est surtout préoccupée du langage et de sa récupération possible. À notre connaissance, notre étude est la première à documenter la réversibilité d'une détérioration mentale avec les caractéristiques d'un syndrome frontal après hémisphérotomie. La chirurgie de l'épilepsie a offert ici une occasion unique de documenter le rôle de l'activité épileptique dans la régression cognitive puisqu'en interrompant brusquement la propagation de l'activité électrique anormale, on a pu comparer la dynamique du développement avant et après l'intervention. La mise en relation des multiples examens cliniques et EEG pratiqués chez un seul enfant sur plusieurs années a permis d'obtenir des informations importantes dans la compréhension des troubles cognitifs et du comportement associés aux épilepsies focales réfractaires. ABSTRACT : A boy with a right congenital hemiparesis due to a left pre-natal middle cerebral artery infarct developed focal epilepsy at 33 months and then an insidious and subsequently more rapid, massive cognitive and behavioural regression with a frontal syndrome between the ages of 4 and 5 years with continuous spike-waves during sleep (CSWS) on the EEG. Both the epilepsy and the CSWS were immediately suppressed by hemispherotomy at the age of 5 years and 4months. A behavioural-cognitive follow-up prior to hemispheratomy, an per-operative EEG and corticography and serial post-operative neuropsychological assessments were performed until the age of 11 years. The spread of the epileptic activity to the "healthy" frontal region was the cause of the reversible frontal syndrome. A later gradual long-term but incomplete cognitive recovery, with moderate mental disability was documented. T9ris outcome is probably explained by another facet of the epilepsy, namely the structural effects of prolonged epileptic dischazges in rapidly developing cerebral networks which are, at the same time undergoing the reorganization imposed by a unilateral early hemispheric lesion. Group studies on the outcome of children before and after hemispherectomy using only single IQ measures, pre- and postoperatively, may miss particular epileptic cognitive dysfunctions as they are likely to be different from case to case. Such detailed and rarely available complementary clinical and EEG data obtained in a single case at different time periods in relation to the epilepsy, including peroperative electrophysiological findings, may help to understand the different cognitive deficits and recovery profiles and the limits of full cognitive recovery.

Selective acquired long QT syndrome (saLQTS) upon risperidone treatment.

ABSTRACT: BACKGROUND: Numerous structurally unrelated drugs, including antipsychotics, can prolong QT interval and trigger the acquired long QT syndrome (aLQTS). All of them are thought to act at the level of KCNH2, a subunit of the potassium channel. Although the QT-prolonging drugs are proscribed in the subjects with aLQTS, the individual response to diverse QT-prolonging drugs may vary substantially. CASE PRESENTATION: We report here a case of aLQTS in response to small doses of risperidone that was confirmed at three independent drug challenges in the absence of other QT-prolonging drugs. On the other hand, the patient did not respond with QT prolongation to some other antipsychotics. In particular, the administration of clozapine, known to be associated with higher QT-prolongation risk than risperidone, had no effect on QT-length. A detailed genetic analysis revealed no mutations or polymorphisms in KCNH2, KCNE1, KCNE2, SCN5A and KCNQ1 genes. CONCLUSIONS: Our observation suggests that some patients may display a selective aLQTS to a single antipsychotic, without a potassium channel-related genetic substrate. Contrasting with the idea of a common target of the aLQTS-triggerring drugs, our data suggests existence of an alternative target protein, which unlike the KCNH2 would be drug-selective.

Vitamin D status in a Brazilian cohort of adolescents and young adults with perinatally acquired human immunodeficiency virus infection

The purpose was to determine the prevalence and related factors of vitamin D (VitD) insufficiency in adolescents and young adults with perinatally acquired human immunodeficiency virus. A cohort of 65 patients (17.6 ± 2 years) at the Federal University of Rio de Janeiro, Brazil, were examined for pubertal development, nutrition, serum parathormone and serum 25-hydroxyvitamin D [s25(OH)D]. s25(OH)D levels < 30 ng/mL (< 75 nmol/L) were defined as VitD insufficiency. CD4+ T-cell counts and viral load, history of worst clinical status, immunologic status as nadir, current immunologic status, and antiretroviral (ART) regimen were also evaluated as risk factors for VitD insufficiency. Mean s25(OH)D was 37.7 ± 13.9 ng/mL and 29.2% had VitD insufficiency. There was no difference between VitD status and gender, age, nutritional status, clinical and immunological classification, and type of ART. Only VitD consumption showed tendency of association with s25(OH)D (p = 0.064). Individuals analysed in summer/autumn season had a higher s25(OH)D compared to the ones analysed in winter/spring (42.6 ± 14.9 vs. 34.0 ± 11.9, p = 0.011). Although, the frequency of VitD insufficiency did not differ statistically between the groups (summer/autumn 17.9% vs. winter/spring 37.8%, p = 0.102), we suggest to monitor s25(OH)D in seropositive adolescents and young adults, especially during winter/spring months, even in sunny regions.

Speech and oromotor deficits of epileptic origin in benign partial epilepsy of childhood with rolandic spikes (BPERS). Relationship to the acquired aphasia-epilepsy syndrome.

The authors report three children who suffered temporary oromotor or speech disturbances as focal epileptic manifestations within the frame of benign partial epilepsy of childhood with rolandic spikes and review similar cases described in the literature. The deficit can occur as an initial symptom of the disorder without visible epileptic seizures and interferes in a variable way with simple voluntary oromotor functions or complex movements including speech production, depending on the exact location and spread of the discharging epileptic focus around the perisylvian region. The most severe deficit produces the anterior operculum syndrome. More subtle non-linguistic deficits such as intermittent drooling, oromotor apraxia or dysfluency, as well as linguistic ones involving phonologic production, can occur. The rapidity of onset, progression and recovery of the deficit is very variable as well as its duration and presumably reflects the degree of epileptic activity. In some cases, rapid improvement with antiepileptic medication occurs and coincidence between the paroxysmal EEG activity (which is usually bilateral) and the functional deficit is seen. The clinical and EEG profile of the seizures disorder and the dynamic of the deficit in these cases bear a strong resemblance to what is seen in the acquired epilepsy-aphasia syndrome (Landau and Kleffner). The variations in clinical symptoms appear more related to the main site, local extension and bilaterality of the epileptic foci rather than a basic difference in physiopathology.

Early-onset acquired epileptic aphasia (Landau-Kleffner syndrome, LKS) and regressive autistic disorders with epileptic EEG abnormalities: the continuing debate.

Early-onset acquired epileptic aphasia (Landau-Kleffner syndrome) may present as a developmental language disturbance and the affected child may also exhibit autistic features. Landau-Kleffner is now seen as the rare and severe end of a spectrum of cognitive-behavioural symptoms that can be seen in idiopathic (genetic) focal epilepsies of childhood, the benign end being the more frequent typical rolandic epilepsy. Several recent studies show that many children with rolandic epilepsy have minor developmental cognitive and behavioural problems and that some undergo a deterioration (usually temporary) in these domains, the so-called "atypical" forms of the syndrome. The severity and type of deterioration correlate with the site and spread of the epileptic spikes recorded on the electroencephalogram within the perisylvian region, and continuous spike-waves during sleep (CSWS) frequently occur during this period of the epileptic disorder. Some of these children have more severe preexisting communicative and language developmental disorders. If early stagnation or regression occurs in these domains, it presumably reflects epileptic activity in networks outside the perisylvian area, i.e. those involved in social cognition and emotions. Longitudinal studies will be necessary to find out if and how much the bioelectrical abnormalities play a causal role in these subgroup of children with both various degrees of language and autistic regression and features of idiopathic focal epilepsy. One has to remember that it took nearly 40 years to fully acknowledge the epileptic origin of aphasia in Landau-Kleffner syndrome and the milder acquired cognitive problems in rolandic epilepsies.

Le QT long acquis [Acquired long QT syndrome].

The long QT syndrome may be acquired or genetically determined. The syndrome is characterized by a prolonged QT interval and is associated with an increased risk of cardiac arrhythmia such as a torsade de pointe and death. Electrolytes disorders such as hypomagnesemia and hypokaliemia and several drugs may increase the risk to develop a long QT syndrome. The epidemiology, the aetiology, the diagnostic approach as well as the management options of an acquired QT prolongation is discussed and reviewed herein.

HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies.

OBJECTIVE: To evaluate deaths from AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (nADM) in the D:A:D Study and to investigate the relationship between these deaths and immunodeficiency. DESIGN: Observational cohort study. METHODS: Patients (23 437) were followed prospectively for 104 921 person-years. We used Poisson regression models to identify factors independently associated with deaths from ADM and nADM. Analyses of factors associated with mortality due to nADM were repeated after excluding nADM known to be associated with a specific risk factor. RESULTS: Three hundred five patients died due to a malignancy, 298 prior to the cutoff for this analysis (ADM: n = 110; nADM: n = 188). The mortality rate due to ADM decreased from 20.1/1000 person-years of follow-up [95% confidence interval (CI) 14.4, 25.9] when the most recent CD4 cell count was <50 cells/microl to 0.1 (0.03, 0.3)/1000 person-years of follow-up when the CD4 cell count was more than 500 cells/microl; the mortality rate from nADM decreased from 6.0 (95% CI 3.3, 10.1) to 0.6 (0.4, 0.8) per 1000 person-years of follow-up between these two CD4 cell count strata. In multivariable regression analyses, a two-fold higher latest CD4 cell count was associated with a halving of the risk of ADM mortality. Other predictors of an increased risk of ADM mortality were homosexual risk group, older age, a previous (non-malignancy) AIDS diagnosis and earlier calendar years. Predictors of an increased risk of nADM mortality included lower CD4 cell count, older age, current/ex-smoking status, longer cumulative exposure to combination antiretroviral therapy, active hepatitis B infection and earlier calendar year. CONCLUSION: The severity of immunosuppression is predictive of death from both ADM and nADM in HIV-infected populations.

Severe Postnatally Acquired Cytomegalovirus Infection Presenting with Colitis, Pneumonitis and Sepsis-Like Syndrome in an Extremely Low Birthweight Infant

Few cases of severe postnatally acquired cytomegalovirus (CMV) infection are reported in premature infants. We report on an extremely low birthweight (ELBW) preterm infant who presented with a sepsis-like syndrome and multiple organ involvement, notably pneumonitis and colitis. The course of infection was assessed by repeated analysis of urine, tracheal aspirates and blood. The patient was given intravenous ganciclovir. The clinical course was rapidly favorable. Development of neutropenia led to the discontinuation of the antiviral treatment after 28 days. Follow-up showed moderate white matter anomalies on cerebral MRI, a transient hypoacusis and a mild developmental delay at 18 months of corrected age. To the best of our knowledge, this is the first description of a severe combination of pneumonitis and colitis in postnatal CMV infection. Many issues remain controversial and are discussed. We propose that antiviral treatment should be considered in severe postnatal CMV infection in ELBW patients.

Strong impact of smoking on multimorbidity and cardiovascular risk among human immunodeficiency virus-infected individuals in comparison with the general population.

Background.  Although acquired immune deficiency syndrome-associated morbidity has diminished due to excellent viral control, multimorbidity may be increasing among human immunodeficiency virus (HIV)-infected persons compared with the general population. Methods.  We assessed the prevalence of comorbidities and multimorbidity in participants of the Swiss HIV Cohort Study (SHCS) compared with the population-based CoLaus study and the primary care-based FIRE (Family Medicine ICPC-Research using Electronic Medical Records) records. The incidence of the respective endpoints were assessed among SHCS and CoLaus participants. Poisson regression models were adjusted for age, sex, body mass index, and smoking. Results.  Overall, 74 291 participants contributed data to prevalence analyses (3230 HIV-infected; 71 061 controls). In CoLaus, FIRE, and SHCS, multimorbidity was present among 26%, 13%, and 27% of participants. Compared with nonsmoking individuals from CoLaus, the incidence of cardiovascular disease was elevated among smoking individuals but independent of HIV status (HIV-negative smoking: incidence rate ratio [IRR] = 1.7, 95% confidence interval [CI] = 1.2-2.5; HIV-positive smoking: IRR = 1.7, 95% CI = 1.1-2.6; HIV-positive nonsmoking: IRR = 0.79, 95% CI = 0.44-1.4). Compared with nonsmoking HIV-negative persons, multivariable Poisson regression identified associations of HIV infection with hypertension (nonsmoking: IRR = 1.9, 95% CI = 1.5-2.4; smoking: IRR = 2.0, 95% CI = 1.6-2.4), kidney (nonsmoking: IRR = 2.7, 95% CI = 1.9-3.8; smoking: IRR = 2.6, 95% CI = 1.9-3.6), and liver disease (nonsmoking: IRR = 1.8, 95% CI = 1.4-2.4; smoking: IRR = 1.7, 95% CI = 1.4-2.2). No evidence was found for an association of HIV-infection or smoking with diabetes mellitus. Conclusions.  Multimorbidity is more prevalent and incident in HIV-positive compared with HIV-negative individuals. Smoking, but not HIV status, has a strong impact on cardiovascular risk and multimorbidity.

Darunavir: A Critical Review of Its Properties, Use and Drug Interactions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Patologia do Coração na AIDS. Estudo de 73 Necropsias Consecutivas

Purpose - To study the incidence and the etiology of the cardiac lesions in AIDS patients. Methods - The autopsy protocols and the filled slides of the heart from 73 consecutive AIDS patients were reviewed. There were, at least, 2 slides of each heart stained by haematoxylin-eosin; when indicated, Ziehl-Nielsen, Gram and Gomori Grocott stains were used. Results - No cause of death was assigned to the heart. There was involvement of the heart in 66 (90%) cases. Marked atrophy of cardiac fibers with or without lipomatosis was observed in 38 patients. Interstitial infiltrates of myocardium were present in 38 necropsies and in 13 of these cases a probable pathogen was demonstrated: cryptococcus neoforms in three cases and mycobacteria tuberculosis, atypical mycobacteria, toxoplasma gondii, trypanosoma cruzi and cytomegalovirus in two cases each. Bacterial endocarditis was found in 4 autopsies and Kaposi sarcome in one. The pericardium was involved in 22 cases; in 12 there was only non specific mononuclear infiltration. Conclusion - Autopsy examination of the heart from AIDS patients revealed frequent pathologic involvement.

Manifestações otorrinolaringológicas em crianças com AIDS

Introduction: The study of otolaryngologic manifestations in children HIV + can lead to early diagnosis of AIDS, allowing specific treatment, responsible by reduced morbidity and mortality. Objectives: Detect the otolaryngologic manifestations in children with AIDS and alert to the importance of the early diagnosis. Study design: Clinical prospective. Material and method: We evaluated 22 children with AIDS assisted at Faculdade de Medicina de Botucatu (São Paulo, Brasil). The medical records were reviewed and the children were submitted to otolaryngologic and hearing acuity exams. Results: We evaluated 12 boys and 10 girls, whose ages ranged from 8 months to 12 years. In B and C clinical classification were included 18 children who were using anti-retroviral medicaments. Physical examination mainly indicated cervical lymphadenopathy (18 cases), paleness of the nasal mucous membrane with abundant mucous secretion over the nasal epithelium (15 cases) and retraction of tympanic membranes (seven cases). The main otolaryngologic diagnoses were: rhinosinusitis (16 cases), oral candidiasis (13 cases), inadequate eustachian tube function (seven cases) and recurrent tonsillar infections (six cases). Conductive hearing loss were detected in 4 children. No child presented sensorineural hearing loss. Conclusions: The main otolaryngologic manifestations presented by the children with HIV virus were rhinosinusitis, oral candidiasis, inadequate eustachian tube function and recurrent tonsillar infections. The allergic aspect of the nasal mucous membrane and the cervical lymphadenopathy were frequent signs and could alert the otolaryngologyst to AIDS during the exam.

Cryptosporidiosis of the biliary tract mimicking pancreatic cancer in an AIDS patient

Diarrhea caused by Cryptosporidium sp is frequent in patients with AIDS, but involvement of other organs of the digestive tract is uncommon. We report a case of Cryptosporidium-associated obstruction of the biliary tract mimicking cancer of the head of the pancreas in a 43-year-old woman with AIDS.