Enfermedad mínima residual en leucemia mieloide aguda no promielocítica: Resultados preliminares de un estudio colaborativo internacional / Minimal residual disease in non-myelocytic acute myeloid leukemia: preliminary results of an international collaborative study

A pesar de los avances en los protocolos de tratamiento y en las medidas de soporte en pacientes con Leucemia Mieloide Aguda (LMA), 27% presentan recaídas de la enfermedad. Esto se debe, entre otras causas, a la persistencia de pequeñas cantidades de células malignas (blastos) resistentes a la terapia. Estas pequeñas cantidades de blastos remanentes se denominan Enfermedad Mínima Residual (EMR). La determinación de EMR requiere de técnicas no solo muy sensibles, sino también específicas, y permite evaluar la respuesta individual a la terapia. La introducción de la EMR como parámetro de respuesta y estratificación está bien definida en Leucemia Linfoblástica Aguda (LLA). Por el contrario, aunque existen publicaciones sobre el impacto pronóstico de la EMR en LMA, aún no se encuentra incluida en forma sistemática en los protocolos nacionales actuales, entre otros motivos, por lo laborioso de la determinación y por la necesidad de validación de la misma. Debe tenerse en cuenta que el inmunofenotipo de los blastos mieloides suele ser más heterogéneo que el de los blastos en LLA, presentando, en muchos casos, subpoblaciones diferentes entre sí, lo cual dificulta su detección certera y no hay consenso definido en cuanto a la metodología más eficaz. En este trabajo describimos una nueva estrategia de marcación y análisis estandarizada en un estudio multicéntrico internacional para LMA y la utilidad de la EMR como parámetro de respuesta y de estratificación. Asimismo, detallamos los resultados preliminares de nuestra cohorte de pacientes (AU)

Despite the improvement in treatment and supportive care of patients with Acute Myeloid Leukemia (AML), 27% of them relapse. This is due to the persistence of small amounts of malignant cells (blasts) resistant to therapy, among other causes. These small amounts of blasts are called Minimal Residual Disease (MRD). The determination of MRD requires not only techniques with high sensitivity but also with high specificity, and allows to evaluate the individual response to treatment. The introduction of MRD as a response parameter is well established in Acute Lymphoblastic Leukemia (ALL), and it is used in current stratification protocols. On the other hand, even though there are some reports regarding the prognostic impact of MRD in AML, it is still not included in the current national protocols due to the lack of validation of the determination, among other causes. This is due to the fact that the immunophenotype of myeloid blasts is more heterogeneous than in ALL, presenting different subpopulations, which difficults their accurate detection. Thus, there is still no consensus regarding the most effective approach. In this article, we describe a new staining and analysis strategy standardized by an international multicentric study, and the utility of EMR as a response and stratification parameter. Additionally, we show the preliminary results of our patient cohort. (AU)

Cancer burden in adolescents and young adults in Europe.

BACKGROUND: Cancer epidemiology is unique in adolescents and young adults (AYAs; aged 15-39 years). The European Society for Medical Oncology/European Society for Paediatric Oncology (ESMO/SIOPE) AYA Working Group aims to describe the burden of cancers in AYAs in Europe and across European Union (EU) countries. PATIENTS AND METHODS: We used data available on the Global Cancer Observatory. We retrieved crude and age-standardised (World Standard Population) incidence and mortality rates. We reported about AYA cancer burden in Europe and between 28 EU member states. We described incidence and mortality for all cancers and for the 13 cancers most relevant to the AYA population. RESULTS: Incidence and mortality varied widely between countries with the highest mortality observed in Eastern EU countries. Cancers of the female breast, thyroid and male testis were the most common cancers across countries followed by melanoma of skin and cancers of the cervix. Variations in cancer incidence rates across different populations may reflect different distribution of risk factors, variations in the implementation or uptake of screening as well as overdiagnosis. AYA cancer mortality disparities may be due to variation in early-stage diagnoses, different public education and awareness of cancer symptoms, different degrees of access or availability of treatment. CONCLUSIONS: Our results highlight the future health care needs and requirements for AYA-specialised services to ensure a homogeneous treatment across different countries as well as the urgency for preventive initiatives that can mitigate the increasing burden.

Scanning the solutions for the sustainable supply of forest ecosystem services in Europe.

Forests are key components of European multifunctional landscapes and supply numerous forest ecosystem services (FES) fundamental to human well-being. The sustainable provision of FES has the potential to provide responses to major societal challenges, such as climate change, biodiversity loss, or rural development. To identify suitable strategies for the future sustenance of FES, we performed a solution scanning exercise with a group of transdisciplinary forest and FES experts from different European regions. We identified and prioritized fifteen major challenges hindering the balanced provision of multiple FES and identified a series of potential solutions to tackle each of them. The most prominent challenges referred to the increased frequency and impacts of extreme weather events and the normative mindset regarding forest management. The respective solutions pointed to the promotion of forest resilience via climate-smart forestry and mainstreaming FES-oriented management through a threefold strategy focusing on education, awareness raising, and networking. In a subsequent survey, most solutions were assessed as highly effective, transferable, monitorable, and with potential for being economically efficient. The implementation of the solutions could have synergistic effects when applying the notion of leverage points. Seven emerging pathways towards the sustainable supply of FES have been identified. These pathways build on each other and are organized based on their potential for transformation: (1) shifting forest management paradigms towards pluralistic ecosystem valuation; (2) using integrated landscape approaches; (3) increasing forest resilience; (4) coordinating actions between forest-related actors; (5) increasing participation in forest planning and management; (6) continuous, open, and transparent knowledge integration; and (7) using incentive-based instruments to support regulating and cultural FES. These pathways can contribute to the implementation of the new EU Forestry Strategy to support the balanced supply of multiple FES. Supplementary Information: The online version contains supplementary material available at 10.1007/s11625-022-01111-4.

Association between hippocampal structure and serum Brain-Derived Neurotrophic Factor (BDNF) in healthy adults: A registered report.

The hippocampus is a highly plastic brain structure supporting functions central to human cognition. Morphological changes in the hippocampus have been implicated in development, aging, as well as in a broad range of neurological and psychiatric disorders. A growing body of research suggests that hippocampal plasticity is closely linked to the actions of brain-derived neurotrophic factor (BDNF). However, evidence on the relationship between hippocampal volume (HCV) and peripheral BDNF levels is scarce and limited to elderly and patient populations. Further, despite evidence that BDNF expression differs throughout the hippocampus and is implicated in adult neurogenesis specifically in the dentate gyrus, no study has so far related peripheral BDNF levels to the volumes of individual hippocampal subfields. Besides its clinical implications, BDNF-facilitated hippocampal plasticity plays an important role in regulating cognitive and affective processes. In the current registered report, we investigated how serum BDNF (sBDNF) levels relate to volumes of the hippocampal formation and its subfields in a large sample of healthy adults (N = 279, 160 f) with a broad age range (20-55 years, mean 40.5) recruited in the context of the ReSource Project. We related HCV to basal sBDNF and, in a subsample (n = 103, 57 f), to acute stress-reactive change in sBDNF. We further tested the role of age as a moderator of both associations. Contrary to our hypotheses, neither basal sBDNF levels nor stress-reactive sBDNF change were associated with total HCV or volume of the dentate gyrus/cornu ammonis 4 (DG/CA4) subfield. We also found no evidence for a moderating effect of age on any of these associations. Our null results provide a first point of reference on the relationship between sBDNF and HCV in healthy mid-age, in contrast to patient or aging populations. We suggest that sBDNF levels have limited predictive value for morphological differences of the hippocampal structure when notable challenge to its neuronal integrity or to neurotrophic capacity is absent.

Foot and ankle measurements on cone beam weightbearing computed tomography.

Over the last years, an increased number of studies have reported the use of cone beam weightbearing computed tomography (WBCT) in the assessment of foot and ankle pathology. This new technology has enabled to overcome the limits inherently related to two-dimensional radiographs (superimposition bias, operator-related bias, rotation bias) and to obtain images reproducing the bones and joints anatomy during physiological standing with a low radiation dose. We performed a review of the current literature to summarize the evidence about the use of 2D or 3D measurements on WBCT images in various foot and ankle conditions. Our aims were to describe measurements proposed so far and to report data on reliability and validity from primary authors.

Blood loss and transfusion rate in patients undergoing two-stage exchange in infected total knee arthroplasty.

Two-stage exchange in infected total knee arthroplasty is a reliable technique, but it has a high rate of blood loss. The study aims to compare the pre-operative and post-operative haemoglobin levels, the rate of transfusion, and the blood loss in two-stage exchange. From July 2018 to July 2019, eighteen patients underwent two-stage exchange of their infected total knee arthroplasty. Local and systemic tranexamic acid was administered in both surgical stages. Calculated blood loss was 2246 mL (range 1528 - 2850) in the first stage and 2388 mL (1873 - 2829) during reimplantation, respectively. The corresponding transfusion rate was 55 % and 67%, respectively. With the numbers available, these differences were not significant. In conclusion, this study shows that the blood loss and transfusion rate are similar during the two stages of exchange knee arthroplasty for infection.

Use of synthetic cartilage implant (Cartiva®) for degeneration of the first and second metatarsophalangeal joint: what is the current evidence?

Polyvinyl alcohol hydrogel implants (also known as Synthetic Cartilage Implant or Cartiva® have been described in the treatment of degeneration of the first and second metatarsophalangeal joint (MTPJ). We reviewed literature to report characteristics of devices on the market and investigate their efficacy and safety. Following the PRISMA checklist, the Medline and Scopus databases were searched, including studies reporting use of Cartiva® for treating joint degeneration of the first and second MPTJ. Studies were searched for surgical technique, postoperative protocol, clinical scores, complications and reoperations. We found that, although some studies suggest that the use of Synthetic Cartilage Implant (Cartiva® is effective in the treatment of hallux rigidus in providing symptoms relief without sacrifice of joint motion, the redundancy of cohorts reported in studies and the frequency of conflict of interest reported by authors weaken the strength of evidence available and warrant further studies. Regarding the treatment of the second MTPJ ailments, no recommendation can be formulated to date due to the lack of primary studies.

Volar distal radius vascularized bone graft vs non-vascularized bone graft: a prospective comparative study.

The pseudoarthrosis (PSA) of scaphoid leads to alteration in load transfer in the wrist joint. Its treatment aims to achieve consolidation to improve clinical complaints and prevent post-traumatic arthritis. The indication for using vascularized bone grafts is still controversial. This prospective comparative study aimed to compare consolidation rate and time to healing of scaphoid PSA treated by volar distal radius vascularized bone graft vs non-vascularized iliac bone graft. Nine patients underwent vascularized grafting of scaphoid PSA. These patients were compared to a control group consisting of twelve patients treated with iliac crest-free bone graft. PSA consolidation was obtained in 8 of 9 patients (88%) and 9 of 12 patients (75%) in the study and control group, respectively. The difference in consolidation rate was not significant. Two of three patients with AVN of the proximal pole in the study group (66%) went to consolidation. In the control group no patient with AVN obtained bone consolidation. This difference almost reached statistical significance (p = 0.083). The mean time to consolidation was 8.6 weeks (range 8-11) and 11.7 weeks (range 10-16), respectively, in the study and control group. This difference was significant (p < 0.05). In conclusion, the distal radius vascularized graft led to satisfactory consolidation rate of PSA in the current study, even in cases of AVN of the proximal pole. Moreover, the vascularized bone graft resulted in shorter healing time compared to the non-vascularized graft.

Partial wrist denervation versus total wrist denervation: A systematic review of the literature.

The aim of this systematic review was to understand which procedure-total or partial wrist denervation-provides better results in terms of pain relief and function. This review was registered on PROSPERO (CRD42018088856). We searched the Medline (PubMed), Web of Science and Scopus databases. Twenty-one studies were included in this review. We assessed the quality of the studies using the Coleman Methodological Score. Data on demographics, surgical indications, diagnostic methods, follow-up periods, type and rates of complications, survivorship of the procedure, return to work, and outcome measures were recorded. A total of 1065 patients were included in this review; the mean quality of the studies included was considered poor. The outcomes could not be analyzed because none of the studies had reliable outcome data reported, but both procedures were effective in terms of pain relief and range of motion. Partial wrist denervation has an average subsequent procedure rate of 19%. Total wrist denervation had an average subsequent procedure rate of 4.7%. No complications were reported in any patient who underwent partial wrist denervation versus 20 patients who underwent total wrist denervation. Both partial and total wrist denervation are safe and reliable procedures that can provide good pain relief and preserve wrist range of motion. Total wrist denervation offers better long-term outcomes in term of pain relief, with fewer subsequent procedures being needed compared to partial denervation, and with a low complication rate. LEVEL OF EVIDENCE: Level III, Systematic review, Therapeutic.

The ALMANACH Project: Preliminary results and potentiality from Afghanistan.

INTRODUCTION: ALMANACH (ALgorithms for the MANagement of Acute CHildhood illnesses) is an electronic version of IMCI (Integrated Management of Childhood Illness) running on tablets. ALMANACH enhances its concept, it integrates well into health staff's daily consultation work and facilitates diagnosis and treatment. ALMANACH informs when to refer a child or to perform a rapid diagnostic test (RDT), recommends the right treatment dosage and synchronizes collected data real time with a Health Management Information System (DHIS2) for epidemiological evaluation and decision making. OBJECTIVES: Since May 2016, ALMANACH is under investigational deployment in three primary health care facilities in Afghanistan with the goal to improve the quality of care provided to children between 2 months and 5 years old. METHODS: IMCI's algorithms were updated in considering latest scientific publications, national guidelines, innovations in RDTs, the target population's epidemiological profile and the local resources available. Before the implementation of the project, a direct observation of 599 consultations was carried out to assess the daily performance at three selected health facilities in Kabul. RESULTS: The baseline survey showed that nutritional screening, vitamin A supplementation and deworming were not systematically performed: few patients were diagnosed for malnutrition (1.8%), received vitamin A (2.7%) or deworming (7.5%). Physical examination was appropriate only for 23.8% of the diagnoses of respiratory or gastrointestinal diseases, ear infection and sore throat. Respiratory rate was checked only in 33.5% of the children with fever and cough, dehydration status was assessed in only 16.5% of the diarrhoea cases. Forty-seven percent of patients received incorrect treatment. Sixty-four percent of the children, before the introduction of ALMANACH, received at least one antibiotic, although for 87.1% antibiotic therapy was unnecessary. The review of 8'047 paediatric consultations between May 2016 and September 2017 showed that with ALMANACH, malnutrition detection, deworming and Vitamin A supplementation increased respectively to 4.4%, 50.2% and 27.5%. Antibiotic prescription decreased to 21.83% and all children were examined and treated in compliance with the protocols. CONCLUSION: A survey will be conducted one year after the implementation to validate these initial promising results. If the efficacy of the approach is confirmed, ALMANACH could establish as a powerful innovation for primary health care.

An original fibular shortening osteotomy technique in tibiotalar arthrodesis.

Tibiotalar arthrodesis (TTA) is the gold-standard treatment for advanced ankle osteoarthritis. We describe an original fibular shortening osteotomy (FSO) performed during TTA, to allow complete talar ascension and reduce the nonunion rate. Forty-two FSOs were associated to TTA (19 fixed by cross-screwing and 23 by anatomic plates) and assessed clinically and radiographically. At 24.7 months' follow-up, fusion rates were 97.6% for TTA and 100% for FSO, with mean fusion time of 5.2 months. One infection and 1 nonunion (4.7%) required further surgery, with complete resolution. Radiological and clinical outcome in TTA, lack of specific complications of FSO and ease of implementation encourage us to publish the technique.

[Disseminated BCG disease revealing a partial deficiency in receptor 1 interferon gamma]. / Bécégite disséminée révélatrice d'un déficit partiel en récepteur 1 de l'interféron gamma.

We report on a case of disseminated BCGitis with an unusual presentation in a 4-month-old infant revealing a syndrome of Mendelian susceptibility to mycobacteria due to a partial dominant mutation of the interferon gamma receptor 1 gene.

Temporal lobe grey matter volume in schizophrenia is associated with a genetic polymorphism influencing glycogen synthase kinase 3-ß activity.

At the crossroad of multiple pathways regulating trophism and metabolism, glycogen synthase kinase (GSK)3 is considered a key factor in influencing the susceptibility of neurons to harmful stimuli (neuronal resilience) and is a target for several psychiatric drugs that directly inhibit it or increase its inhibitory phosphorylation. Inhibition of GSK3 prevents apoptosis and could protect against the neuropathological processes associated with psychiatric disorders. A GSK3-beta promoter single-nucleotide polymorphism (rs334558) influences transcriptional strength, and the less active form was associated with less detrimental clinical features of mood disorders. Here we studied the effect of rs334558 on grey matter volumes (voxel-based morphometry) of 57 patients affected by chronic schizophrenia. Carriers of the less active C allele variant showed significantly higher brain volumes in an area encompassing posterior regions of right middle and superior temporal gyrus, within the boundaries of Brodmann area 21. The temporal lobe is the brain parenchymal region with the most consistently documented morphometric abnormalities in schizophrenia, and neuropathological processes in these regions develop soon at the beginning of the illness. These results support the interest for GSK3-beta as a factor affecting neuropathology in major behavioural disorders, such as schizophrenia, and thus as a possible target for treatment.

Outcomes of prenatally diagnosed tetralogy of Fallot: Implications for valve-sparing repair versus transannular patch.

OBJECTIVES: To assess outcomes of prenatally diagnosed tetralogy of Fallot and determine factors associated with the choice to undergo a valvesparing repair versus transannular patch, and the use of prostaglandins at birth. METHODS: All cases at The Hospital for Sick Children (Toronto, Ontario) with a fetal diagnosis of tetralogy of Fallot from 1998 to 2006, were reviewed for demographic and fetal echocardiographic data to determine factors associated with the valve-sparing repair and need for perinatal support. RESULTS: Sixty-four fetuses met inclusion criteria (median gestational age 22 weeks) with 47 live births. Twenty-six underwent valve-sparing repair (median age 5.7 months) and 14 underwent transannular patch repair (median age 4.5 months). There were seven deaths before surgery and one post-transannular patch repair. One patient required a transannular patch repair after the initial valve-sparing repair. Twelve of 29 (41%) patients received prostaglandins at birth. Type of surgical repair, use of prostaglandins and postnatal death were among the outcomes investigated. The mean pulmonary valve (PV) z-score was -3.0+/-2.0 and the mean PV/aortic valve (AoV) ratio was 0.65+/-0.10. Lower PV z-score (P=0.04), smaller PV/AoV ratio (P=0.04) and the presence of nonantegrade arterial duct flow (P=0.02) were associated with prostaglandin use. A higher PV/AoV ratio was associated with valvesparing repair (P=0.04). Fetal z-scores of the PV, AoV and right pulmonary artery at 29 to 32 weeks gestational age correlated with respective postnatal z-scores (P=0.01). CONCLUSION: Fetal echocardiographic variables were associated with the use of prostaglandins and valve-sparing repair in fetuses with tetralogy of Fallot, and at 29 weeks, correlated with postnatal valve diameters.

Changes in medial prefrontal cortex neural responses parallel successful antidepressant combination of venlafaxine and light therapy.

Few pilot prospective studies performed BOLD fMRI before and after treatment in order to define the neural correlates of antidepressant response. To determine how antidepressant treatment influences the pattern of neural response to a task targeting the depressive biases in information processing (moral valence decision), eight depressed inpatients were treated with combined venlafaxine and light therapy for four weeks. Brain BOLD functional magnetic resonance imaging on a 3.0 Tesla scanner was performed before and after treatment. Treatment and moral value of the stimuli showed the most significant interaction in right medial frontal gyrus (BA 10), where also clinical status was found to be inversely correlated with response to negative stimuli after treatment. A significant interaction of treatment and valence of the stimuli was also detected in other areas that have been widely associated with the depressive illness.

Leucemias agudas pediátricas de inmunofenotipo inusual / Childhood acute leukemias of unusual phenotype

La mayoría de las Leucemias Agudas (LA) pediátricas pueden clasificarse como Linfoblásticas (principalmente de fenotipo B o T) o Mieloblásticas dependiendo del linaje celular de los blastos, recibiendo tratamiento específico de acuerdo a esta caracterización. La inmunotipificación de las LA se basa en la evaluación de la expresión de antígenos de superficie y/o intracitoplasmáticos de diferenciación linfoide (B o T) o mieloide (My) en los blastos, lo cual permite definir la estirpe celular y clasificar la LA de acuerdo al grado de maduración. Sin embargo, existen grupos particulares poco frecuentes de LA cuya clasificación resulta dificultosa y por eso se las denomina LA de linaje ambiguo (fenotipo mixto/indiferenciadas) y LA de linaje dendrítico. Las de fenotipo mixto son aquellas en las que los blastos expresan marcadores de más de un linaje, y las indiferenciadas aquellas que no expresan antígenos específicos para ningún linaje. Diferentes convenciones se han ido desarrollando para definir y clasificar estos fenotipos inusuales, siendo la más actualizada la propuesta por la Organización Mundial de la Salud (2008). De acuerdo a estas pautas, de 1301 casos de LA diagnosticados entre abril de 1994 y abril de 2009, 28 fueron re-clasificados como LA de linaje Ambiguo, 3 como leucemia mieloide aguda minimamente diferenciadas y 3 como LA de células dendríticas. Debido a lo infrecuente de estos casos, su caracterización resulta relevante, ya que la bibliografía presenta, en general, sólo comunicaciones esporádicas de estos fenotipos particulares. Dada la importante casuística del Hospital Garrahan y el amplio seguimiento de los pacientes, el relevamiento de estos casos inusuales permite caracterizarlos desde el inmunofenotipo, la morfología/citoquímica, la citogenética/biología molecular y evaluar su presentación clínica, evolución, respuesta al tratamiento y sobrevida libre de eventos con la finalidad de colaborar con la definición de su pronóstico y eventualmente con la elaboración de protocolos de tratamiento diferenciados para estos subgrupos de LA (AU)

The majority of childhood acute leukemias (AL) can be classified as lymphoblastic (mainly phenotype B or T) or myeloblastic, depending on the cell lineage of the blasts, requiring specific treatment according to this characterization. Immunotypification of AL is based on surface and/or intracytoplasmic antigen expression with lymhoid (B or T) or myeloide (My) blast differentiation, allowing definition of cell lineage and classification of the AL according to the grade of maturation. Nevertheless, there are rare cases of AL that are difficult to classify, denominated AL of ambiguous lineage (mixed/undifferentiated lineage) and acute dendritic cell leukemia. In AL of the mixed phenotype, the blasts express markers of more than one lineage and in undifferentiated AL, the blasts lack antigen expression of any specific lineage. Different conventions have tried to define and classify these unusual phenotypes, among which the most recent proposal of the World Health Organization (2008). According to the criteria of the latter, of 1301 cases of AL diagnosed between April 1994 and April 2009, 28 were re-classified as AL of ambiguous lineage, 3 as minimally differentiated acute myeloid leukemia, and 3 as acute dendritic cell leukemia. Characterization of these cases is important, as in the literature only sporadic reports of these rare phenotypes are found. Given the large number of patients with a long follow-up of the Garrahan Hospital, a review of these unusual cases allowed characterization from the point of view of the immunophenotype, morphology/cytochemistry, cytogenetics/molecular biology and to evaluate clinical presentation, evolution, response to treatment, and event-free survival to help define the prognosis and develop protocols for the treatment of these subgroups of AL (AU)

A 475 years-old founder effect involving IL12RB1: a highly prevalent mutation conferring Mendelian Susceptibility to Mycobacterial Diseases in European descendants.

Mutations in IFNGR1, IFNGR2, IL12RB1, IL12B, STAT1 and NEMO result in a common clinical phenotype known as Mendelian Susceptibility to Mycobacterial Diseases (MSMD). Interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency is the most common genetic etiology for MSMD. Known mutations affecting IL12RB1 are recessively inherited and are associated with null response to both IL-12 and IL-23. Mutation IL12RB1 1623_1624delinsTT was originally described in 5 families from European origin (2 from Germany; 1 from Cyprus, France and Belgium). Interestingly, this same mutation was found in an unexpectedly high prevalence among IL-12Rbeta1 deficient patients in Argentina: 5-out-of-6 individuals born to unrelated families carried this particular change. To determine whether mutation 1623_1624delinsTT represents a DNA mutational hotspot or a founder effect, 34 polymorphic markers internal or proximal to IL12RB1 were studied in the Argentinean and the Belgian patients. A common haplotype spanning 1.45-3.51Mb was shared by all chromosomes carrying mutation 1623_1624delinsTT, and was not detected on 100 control chromosomes. Applying a modified likelihood-based method the age of the most recent common ancestor carrying mutation 1623_1624delinsTT was estimated in 475 years (95% CI, 175-1275), which is the time when the Spaniards initiated the colonization of the Americas. Mutation 1623_1624delinsTT represents the first founder effect described on IL-12Rbeta1, the most frequently affected gene in MSMD, and affecting patients with European ancestors. The reason(s) behind the persistency of this mutation across multiple generations, its relative high prevalence, and any potential selective advantage are yet to be established.

Longitudinal and cross-sectional analysis of atrophy in pharmacoresistant temporal lobe epilepsy.

BACKGROUND: Whether recurrent epileptic seizures induce brain damage is debated. Disease progression in epilepsy has been evaluated only in a few community-based studies involving patients with seizures well controlled by medication. These studies concluded that epilepsy does not inevitably lead to global cerebral damage. OBJECTIVE: To track the progression of neocortical atrophy in pharmacoresistant temporal lobe epilepsy (TLE) using longitudinal and cross-sectional designs. METHODS: Using a fully automated measure of cortical thickness on MRI, we studied a homogeneous sample of patients with pharmacoresistant TLE. In the longitudinal analysis (n = 18), fixed-effect models were used to quantify cortical atrophy over a mean interscan interval of 2.5 years (range = 7 to 90 months). In the cross-sectional analysis (n = 121), we correlated epilepsy duration and thickness. To dissociate normal aging from pathologic progression, we compared aging effects in TLE to healthy controls. RESULTS: The longitudinal analysis mapped progression in ipsilateral temporopolar and central and contralateral orbitofrontal, insular, and angular regions. In patients with more than 14 years of disease, atrophy progressed more rapidly in frontocentral and parietal regions that in those with shorter duration. The cross-sectional study showed progressive atrophy in the mesial and superolateral frontal, and parietal cortices. CONCLUSIONS: Our combined cross-sectional and longitudinal analysis in patients with pharmacoresistant temporal lobe epilepsy demonstrated progressive neocortical atrophy over a mean interval of 2.5 years that is distinct from normal aging, likely representing seizure-induced damage. The cumulative character of atrophy underlies the importance of early surgical treatment in this group of patients.