Diagnosis, treatment, and management of rickets: a position statement from the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology.

Rickets results from impaired mineralization of growing bone due to alterations in calcium and phosphate homeostasis. Clinical signs of rickets are related to the age of the patient, the duration of the disease, and the underlying disorder. The most common signs of rickets are swelling of the wrists, knees or ankles, bowing of the legs (knock-knees, outward bowing, or both) and inability to walk. However, clinical features alone cannot differentiate between the various forms of rickets. Rickets includes a heterogeneous group of acquired and inherited diseases. Nutritional rickets is due to a deficiency of vitamin D, dietary calcium or phosphate. Mutations in genes responsible for vitamin D metabolism or function, the production or breakdown of fibroblast growth factor 23, renal phosphate regulation, or bone mineralization can lead to the hereditary form of rickets. This position paper reviews the relevant literature and presents the expertise of the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP). The aim of this document is to provide practical guidance to specialists and healthcare professionals on the main criteria for diagnosis, treatment, and management of patients with rickets. The various forms of rickets are discussed, and detailed references for the discussion of each form are provided. Algorithms to guide the diagnostic approach and recommendations to manage patients with rare forms of hereditary rickets are proposed.

Low Levels of Serum Total Vitamin B12 Are Associated with Worse Metabolic Phenotype in a Large Population of Children, Adolescents and Young Adults, from Underweight to Severe Obesity.

Vitamin B12 (or cobalamin) is an essential vitamin for DNA synthesis, fatty acid and protein metabolism as well as other metabolic pathways fundamental to the integrity of cells and tissues in humans. It is derived from the diet and mostly stored in the liver. Its deficiency has been associated with metabolic derangements, i.e., obesity, glucose intolerance, increased lipogenesis and metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH). However, data with regard to body weight across the whole spectrum (from underweight to severe obesity) in children and young individuals are scarce. The present study aims to describe the association between serum total vitamin B12 and body mass index (BMI) ranging from underweight to severe obesity in a large population of children, adolescents and young adults. This study also investigates associations with visceral adiposity, glucose and lipid metabolism and liver dysfunction. A cross-sectional, single-centre study was conducted at the Paediatrics and Endocrinology units of the "Bambino Gesù Children Hospital", a tertiary referral institution for eating disorders. Clinical charts were reviewed and 601 patients aged from 5 to 25 years were enrolled in order to analyse anthropometric, auxological, clinical, biochemical and liver ultrasound data using robust statistical approaches. Analyses were adjusted for potential confounders. A reduction in serum total B12 levels was associated with a linear increase in body weight, as expressed by WHO BMI SDS (r = -0.31, p < 0.001, BCa 95% -0.38, -0.24). Lower B12 levels were associated with higher waist circumference but only in pubertal girls (r = -0.33, p = 0.008, BCa 95% -0.53, -0.11). Hepatic insulin resistance was higher in males with lower B12 levels (B = -0.003 (-0.007, -0.0001), p = 0.039), but not in females, whereas whole-body insulin resistance was unaffected. Serum lipid profiles (total, HDL and LDL cholesterol and triglycerides) were not influenced by serum cobalamin levels. However, lower cobalamin levels were associated with higher grading of ultrasound-scored hepatic steatosis (ptrend = 0.035). Lastly, both AST and ALT showed a significant and direct correlation with total B12 levels in underweight (r = 0.22 and 0.24, p = 0.002 and <0.001, respectively) and severely obese subjects (r = 0.24 and 0.32, p = 0.002 and <0.001). In conclusion lower vitamin B12 levels are associated with higher body weight, adiposity and with worse metabolic health in a large population of children, adolescents and young adults.

Insulin Clearance at the Pubertal Transition in Youth with Obesity and Steatosis Liver Disease.

No data are available on insulin clearance (ClI) trends during the pubertal transition. The aim of this study was to investigate in 973 youths with obesity whether ClI in fasting and post-oral glucose challenge (OGTT) conditions varies at the pubertal transition in relation to the severity of obesity and the presence of steatosis liver disease (SLD). The severity of obesity was graded according to the Centers for Disease Control. SLD was graded as absent, mild and severe based on alanine amino transferase levels. ClI was defined as the molar ratio of fasting C-peptide to insulin and of the areas under the insulin to glucose curves during an OGTT. In total, 35% of participants were prepubertal, 72.6% had obesity class II, and 52.6% had mild SLD. Fasting ClI (nmol/pmol × 10-2) was significantly lower in pubertal [0.11 (0.08-0.14)] than in prepubertal individuals [0.12 (0.09-0.16)] and higher in class III [0.15 (0.11-0.16)] than in class I obesity [0.11 (0.09-0.14)]. OGTT ClI was higher in boys [0.08 (0.06-0.10)] than in girls [0.07 (0.06-0.09)]; in prepubertal [0.08 (0.06-0.11)] than in pubertal individuals [0.07 (0.05-0.09)]; in class III [0.14 (0.08-0.17)] than in class I obesity [0.07 (0.05-0.10)]; and in severe SLD [0.09 (0.04-0.14)] than in no steatosis [0.06 (0.04-0.17)]. It was lower in participants with prediabetes [0.06 (0.04-0.07)]. OGTT ClI was lower in youths with obesity at puberty along with insulin sensitivity and greater secretion. The findings suggest that the initial increase in ClI in youth with severe obesity and SLD is likely to compensate for hyperinsulinemia and its subsequent decrease at the onset of prediabetes and other metabolic abnormalities.

Plasminogen Activator Inhibitor-1 and Vitamin D Association in the Overweight and Obese Pediatric Population.

BACKGROUND: Childhood overweight and obesity have been described by the World Health Organization as noncommunicable diseases and among the greatest public health threats since they have reached epidemic proportions. A child with obesity risks becoming an adult with obesity and developing metabolic and hemostatic disorders which are the basis for the development of coronary heart diseases. Recently, a number of clinical reports have demonstrated that both an increase in plasminogen activator inhibitor-1 (PAI-1) and a deficiency in 25OH-vitamin D3 (VD) are associated with an increase in thrombotic episodes. METHODS: PAI-1 and VD levels were measured in 259 clinically overweight and obese children aged between 2 and 18 years enrolled in the Nutritional Education Program of the Bambino Gesù Children's Hospital and Research Institute of Rome (Italy) and 80 normal-weight subjects. RESULTS: We observed increased HOMA-IR, PAI-1, and other inflammation indices associated with decreased VD levels when compared to normal-weight children. CONCLUSIONS: Our results demonstrated that overweight and obesity are correlated with higher levels of the inflammation index. Moreover, our patients show high PAI-1 and low VD levels, confirming the high thrombotic risk in our pediatric population.

A rare occurrence of non-classic congenital adrenal hyperplasia and type 1 diabetes mellitus in a girl with Prader-Willi Syndrome: Case report and review of the literature.

Prader-Willi syndrome (PWS) is a rare genetic disorder resulting from lack of expression of the paternally derived chromosome 15q11-13, associated with several complications, including pubertal disorders, short stature, hyperphagia, obesity, glucose metabolism abnormalities, scoliosis, obstructive sleep apnea syndrome (OSAS) and behavioral problems. We report the case of a girl affected by PWS who presented at the age of 5.9 with premature pubarche, accelerated linear growth and advanced bone age (BA). She was subsequently diagnosed with non-classic congenital adrenal hyperplasia (CAH) confirmed by genetic analysis. Considering the clinical, biochemical, and genetic findings, hydrocortisone therapy was started to prevent rapid BA acceleration and severe compromission of final height. During infancy, short stature and low levels of insulin-like growth factor-1 (IGF-1) for age and gender led to suspicion of growth hormone deficiency (GHD), confirmed by stimulation testing (arginine and clonidine). rhGH therapy was administered and continued until final height was reached. During endocrinological follow up she developed impaired glucose tolerance with positive markers of ß-cell autoimmunity (anti-glutamic acid decarboxylase antibodies, GAD Ab), which evolved over time into type 1 diabetes mellitus and insulin therapy with a basal-bolus scheme and an appropriate diet were needed.

Study of the Association between Thiols and Oxidative Stress Markers in Children with Obesity.

Obesity has reached epidemic proportions, and the World Health Organization defined childhood overweight and obesity as a noncommunicable disease that represents the most serious public health challenges of the twenty-first century. Oxidative stress, defined as an imbalance between oxidants and antioxidants causing an impairment of the redox signals, is linked to the development of metabolic diseases. In addition, reactive oxygen species generated during metabolic disorder could increase inflammation, causing the development of insulin resistance, diabetes, and cardiovascular disease. We analyze serum levels of cysteine (Cys), cysteinyl-glycine (Cys-Gly), homocysteine (Hcy), and glutathione (GSH), and other markers of oxidative stress, such as thiobarbituric acid reactive substances (T-BARS), 8-isoprostane, and protein carbonyl in our children with obesity. Total antioxidant status was also determined. We found lower GSH and Cys-Gly levels, and higher Hcy and oxidative stress markers levels. We also found a positive correlation between Body Mass Index (BMI), Cys, GSH, and Hcy levels, between insulin and Cys levels, and between BMI and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) with 8-isoprostane levels. Finally, we found a correlation between age and GSH and Cys levels. The deficiency of GSH could be restored by dietary supplementation with GSH precursors, supplying an inexpensive approach to oppose oxidative stress, thus avoiding obesity complications.

Prevalence of prediabetes in children and adolescents by class of obesity.

BACKGROUND: To evaluate prevalence of prediabetes (impaired fasting glucose, IFG; impaired glucose tolerance, IGT; and high glycated haemoglobin, h-HbA1c) in children and adolescents in relation to class of age and obesity; to appraise association with estimates of insulin metabolism, cardiovascular risk factors and alanine aminotransferase (ALT) levels. METHODS: Study of marginal prevalence (i.e., as function of sex, age and obesity class) of isolated and combined IFG, IGT and h-HbA1c in children (age 4-9.9 years) and adolescents (age 10-17.9 years) and association to blood pressure (BP), total, HDL and non-HDL cholesterol, triglycerides, ALT and insulin sensitivity/secretion indexes. RESULTS: Data of 3110 participants (51% males, 33% children; 33% overweight, 39% obesity class I, 20.5% class II, 7.5% class III) were available. Unadjusted prevalence of prediabetes was 13.9% in children (2.1% IFG, 6.7% IGT, 3.9% h-HbA1c, IFG-IGT 0.06%) and 24.6% in adolescents (3.4% IFG, 9.4% IGT, 5.5% h-HbA1c, IFG-IGT 0.09%). Combined h-HBA1c was found in very few adolescents. Prevalence of prediabetes increased significantly by class of obesity up to 20.5% in children and 31.6% in adolescents. Phenotypes of prediabetes were differently but significantly associated with increased systolic and diastolic BP (by 2-7.3 and ~8 mmHg, respectively), triglycerides (by 23-66 mg/dl), and ALT levels (by 10-22 UI/L) depending on the prediabetes phenotype. CONCLUSION AND RELEVANCE: It is worth screening prediabetes in children aged <10 years old with obesity classes II and III and in adolescents. In those with prediabetes, monitoring of blood pressure, triglycerides and ALT levels must be encouraged.

Circulating Extracellular Vesicles Impair Mesenchymal Stromal Cell Differentiation Favoring Adipogenic Rather than Osteogenic Differentiation in Adolescents with Obesity.

Excess body weight has been considered beneficial to bone health because of its anabolic effect on bone formation; however, this results in a poor quality bone structure. In this context, we evaluated the involvement of circulating extracellular vesicles in the impairment of the bone phenotype associated with obesity. Circulating extracellular vesicles were collected from the plasma of participants with normal weight, as well as overweight and obese participants, quantified by flow cytometry analysis and used to treat mesenchymal stromal cells and osteoblasts to assess their effect on cell differentiation and activity. Children with obesity had the highest amount of circulating extracellular vesicles compared to controls. The treatment of mesenchymal stromal cells with extracellular vesicles from obese participants led to an adipogenic differentiation in comparison to vesicles from controls. Mature osteoblasts treated with extracellular vesicles from obese participants showed a reduction in differentiation markers in comparison to controls. Children with obesity who regularly performed physical exercise had a lower circulating extracellular vesicle amount in comparison to those with a sedentary lifestyle. This pilot study demonstrates how the high amount of circulating extracellular vesicles in children with obesity affects the bone phenotype and that physical activity can partially rescue this phenotype.

Bone density and body composition in small for gestational age children with adequate catch up growth: A preliminary retrospective case control study.

BACKGROUND: Fetal growth patterns and birth weight (BW) have been associated with bone mineral density (BMD) and content (BMC) throughout infancy and childhood up to early adulthood. We hypothesized that in small for gestational age (SGA) children, compensatory infant catch-up growth to normal height centiles counteracts the adverse consequences of low BW on bone accrual. AIM: To evaluate BMD and BMC of SGA children born at term who experienced a normal catch-up growth as compared to children born appropriate for gestational age (AGA). PATIENTS: We recruited 53 SGA (26 females) and 60 AGA children (27 females), aged 6 to 18 years, matched for sex and body mass index (BMI). Fat mass (FM); Free fat mass (FFM); Lumbar spine and Total body less head (TBLH) BMD; BMC and BMD standard deviation scores corrected for body size (BMAD, BMAD z-score and TBLH BMD/Height) and TBLH BMC for FFM (TBLHBMC/FFM) were derived from Dual Energy X-ray absorptiometry (DXA) scans. RESULTS: SGA and AGA children did not differ in any auxological, body composition and bone parameters appropriately adjusted for height and FFM. BMI, FM and, remarkably, FFM were significantly correlated with bone mass parameters in both groups while no correlation was found between FM and FFM with the BW SDS in the univariate analysis. CONCLUSION: Our preliminary data demonstrate that SGA children born at term who recover from their growth deficiency through catch-up growth achieve bone mass and body composition not different from children born AGA.

Coupled effects of climate teleconnections on drought, Santa Ana winds and wildfires in southern California.

Projections of future climate change impacts suggest an increase of wildfire activity in Mediterranean ecosystems, such as southern California. This region is a wildfire hotspot and fire managers are under increasingly high pressures to minimize socio-economic impacts. In this context, predictions of high-risk fire seasons are essential to achieve adequate preventive planning. Regional-scale weather patterns and climatic teleconnections play a key role in modulating fire-conducive conditions across the globe, yet an analysis of the coupled effects of these systems onto the spread of large wildfires is lacking for the region. We analyzed seven decades (1953-2018) of documentary wildfire records from southern California to assess the linkages between weather patterns and large-scale climate modes using various statistical techniques, including Redundancy Analysis, Superposed Epoch Analysis and Wavelet Coherence. We found that high area burned is significantly associated with the occurrence of adverse weather patterns, such as severe droughts and Santa Ana winds. Further, we document how these fire-promoting events are mediated by climate teleconnections, particularly by the coupled effects of El Niño Southern Oscillation and Atlantic Multidecadal Oscillation.

Decision-Making, Impulsiveness and Temperamental Traits in Eating Disorders.

OBJECTIVE: To explore decision-making, impulsiveness and temperamental traits in patients suffering from eating disorders (EDs), as compared with healthy controls (HC). METHOD: Fifty-one patients affected by ED (fourteen with anorexia restricting subtype, AN-R; fourteen with bulimia, BN; thirteen with anorexia bingeing/purging subtype, AN-BP; ten with binge-eating disorder, BED) and twenty-eight HC. The patients, recruited at the Section of Psychiatry of the University of Pisa (Italy, were evaluated with a battery of neuropsychological questionnaires, including the IOWA Gambling Task (IGT), the Barratt Impulsiveness Scale (BIS-11), the Temperament and Character Inventory (TCI), the Frontal Assessment Battery (FAB) and the Hamilton Depression Rating Scale (HAM-D). RESULTS: The results indicated that AN-R, AN-BP and BN patients showed poorer IGT performances than HC (p < .05), while BED performances were similar to those of HC. IGT scores suggested the existence of similarities in decision-making performances of AN-BP and BN patients, as they performed differently from HC starting from block 3 (F(16.2)=1.7). In addition, differences between AN-BP/BN and AN-R patients were detected, given that they performed differently starting from block 4. As far as BIS-11 is concerned, AN-BP and BN patients reached the highest BIS total scores, when compared with the other groups. Further, they shared similar temperamental and impulsiveness profiles, as demonstrated by their BIS-11 'motor impulsiveness' scores, and by their TCI 'novelty seeking', 'reward dependence' and 'persistence' dimensions. The post-hoc analyses revealed that both AN groups (namely, AN-R and AN-BP) scored significantly lower than HC on the FAB. No patients fulfilled the criteria for the diagnosis of a current major depression. CONCLUSIONS: Decision-making deficits are common in EDs. In AN-R these seem related to cognitive styles, while in AN-BP and BN patients with temperament features and impulsiveness traits.

Climate change reduces resilience to fire in subalpine rainforests.

Climate change is affecting the distribution of species and the functioning of ecosystems. For species that are slow growing and poorly dispersed, climate change can force a lag between the distributions of species and the geographic distributions of their climatic envelopes, exposing species to the risk of extinction. Climate also governs the resilience of species and ecosystems to disturbance, such as wildfire. Here we use species distribution modelling and palaeoecology to assess and test the impact of vegetation-climate disequilibrium on the resilience of an endangered fire-sensitive rainforest community to fires. First, we modelled the probability of occurrence of Athrotaxis spp. and Nothofagus gunnii rainforest in Tasmania (hereon "montane rainforest") as a function of climate. We then analysed three pollen and charcoal records spanning the last 7,500 cal year BP from within both high (n = 1) and low (n = 2) probability of occurrence areas. Our study indicates that climatic change between 3,000 and 4,000 cal year bp induced a disequilibrium between montane rainforests and climate that drove a loss of resilience of these communities. Current and future climate change are likely to shift the geographic distribution of the climatic envelopes of this plant community further, suggesting that current high-resilience locations will face a reduction in resilience. Coupled with the forecast of increasing fire activity in southern temperate regions, this heralds a significant threat to this and other slow growing, poorly dispersed and fire sensitive forest systems that are common in the southern mid to high latitudes.

How significant is atmospheric metal contamination from mining activity adjacent to the Tasmanian Wilderness World Heritage Area? A spatial analysis of metal concentrations using air trajectories models.

This study investigated metal contamination from historical mining in lakes in the Tasmanian Wilderness World Heritage Area (TWWHA) and surrounding region. The largest increase in sedimentation and metal contamination occurred ca. 1930 when open-cut mining commenced and new mining technology was introduced into the region. The geochemical signal of lake sediments changed from reflecting the underlying geology and lithology to that reflecting mining activities. The HYSPLIT air particle trajectory model explains metal distribution in the lakes, with those in the northwest region closest to the mines having the highest metal contamination. Lake metal concentrations since mining activities commenced are in the order: Owen Tarn > Basin Lake > Perched Lake > Lake Dove > Lake Dobson > Lake Cygnus, with Perched Lake and Lakes Dove, Dobson and Cygnus in the TWWHA. Metal contamination affected centres up to 130 km down-wind of mining sites. Enrichment factors (EF) for Pb, Cu, As and Cd are >1 for all lakes, with Owen Tarn and Basin Lake having very high EFs for Cu and Pb (98 and 91, respectively). Pb, Cu, As and Cd concentrations are above the Australia/New Zealand lower sediment guidelines, with Pb, Cu and As above the high guidelines in Owen Tarn and Basin Lake. This study demonstrated the legacy of metal contamination in the TWWHA by mining activities and the consequences of a lack of execution of environmental regulations by past governments in Tasmania.

Basal levels of 17-hydroxyprogesterone can distinguish children with isolated precocious pubarche.

BACKGROUND: Basal levels of androgens, in particular 17-hydroxyprogesterone (17OHP), are widely debated as predictors of non-classical congenital adrenal hyperplasia (NCCAH) among patients with precocious pubarche (PP). Many authors have recommended the use of adrenocorticotropic hormone (ACTH) stimulation test in children with PP. The aim of our study was to identify clinical and biochemical predictors of NCCAH in children with PP. METHODS: We conducted a prospective study of 92 patients with PP undergoing an ACTH stimulation test. We tested the association of basal clinical and biochemical parameters with NCCAH diagnosis. Patients were suspected to have NCCAH if their stimulated 17OHP plasma levels were >10 ng/mL. In these patients, the diagnosis was confirmed by genetic test. RESULTS: Seven (7.6%) patients resulted having NCCAH. The best basal biochemical predictor for NCCAH was 17OHP level >2 ng/mL. In fact, a basal 17OHP level >2 ng/mL had 100% (95% confidence interval (CI), 59.04-100) sensitivity and 93% (95% CI, 85.3-97.37) specificity. The area under the receiver-operating characteristic curve for 17OHP was 0.99 (95% CI, 0.98-1.007). CONCLUSIONS: Basal 17OHP cut-off of 2 ng/mL was very effective in predicting NCCAH among our patients with PP. Assay-specific cut-off would probably be the best strategy to avoid unnecessary ACTH test.

Molecular Screening of MKRN3, DLK1, and KCNK9 Genes in Girls with Idiopathic Central Precocious Puberty.

BACKGROUND: Mutations in the imprinted gene MKRN3 have been described as a common genetic cause of idiopathic central precocious puberty (CPP), in particular in familial cases. However, the exact prevalence of mutations is unknown. Single nucleotide polymorphisms in 2 other imprinted genes, DLK1 and KCNK9, have been associated with age at menarche. We investigated the prevalence of mutations in MKRN3, DLK1, and KCNK9 genes in a cohort of girls with idiopathic CPP. METHODS: MKRN3, DLK1, and KCNK9 coding regions were sequenced in 60 girls with idiopathic CPP (familial in 23 cases). RESULTS: Three mutations, including a new one, in MKRN3 were found in 2 familial cases (c.1229G>A; p.Cys410Ter and c.477_485del; p.Pro160Cysfs*14) (8.7%) and in 1 sporadic case (c.982C>T; p.Arg328Cys) (2.8%). We did not find rare variants in DLK1 and KCNK9 genes. CONCLUSIONS: (1) The prevalence of MKRN3 mutations in our cohort was similar to that reported in the literature in sporadic cases but lower than previously described in familial ones. This could be due to different inheritance patterns of families studied; (2) we expanded the phenotype of MKRN3 defects describing 3 more patients with MKRN3 mutations; and (3) point mutations in DLK1 and KCNK9 at least do not seem to be a common cause of CPP in girls.

The Role of Electroconvulsive Therapy (ECT) in Bipolar Disorder: Effectiveness in 522 Patients with Bipolar Depression, Mixed-state, Mania and Catatonic Features.

OBJECTIVE: We evaluated the effectiveness of Electroconvulsive Therapy (ECT) in the treatment of Bipolar Disorder (BD) in a large sample of bipolar patients with drug resistant depression, mania, mixed state and catatonic features. METHOD: 522 consecutive patients with DSM-IV-TR BD were evaluated prior to and after the ECT course. Responders and nonresponders were compared in subsamples of depressed and mixed patients. Descriptive analyses were reported for patients with mania and with catatonic features. RESULTS: Of the original sample only 22 patients were excluded for the occurrence of side effects or consent withdrawal. After the ECT course, 344 (68.8%) patients were considered responders (final CGIi score ≤2) and 156 (31.2%) nonresponders. Response rates were respectively 68.1% for BD depression, 72.9% for mixed state, 75% for mania and 80.8% for catatonic features. Length of current episode and global severity of the illness were the only statistically significant predictors of nonresponse. CONCLUSION: ECT resulted to be an effective and safe treatment for all the phases of severe and drug-resistant BD. Positive response was observed in approximately two-thirds of the cases and in 80% of the catatonic patients. The duration of the current episode was the major predictor of nonresponse. The risk of ECT-induced mania is virtually absent and mood destabilization very unlikely. Our results clearly indicate that current algorithms for the treatment of depressive, mixed, manic and catatonic states should be modified and, at least for the most severe patients, ECT should not be considered as a "last resort".

Psychopharmacological options for adult patients with anorexia nervosa.

The aim of this review was to summarize evidence from research on psychopharmacological options for adult patients with anorexia nervosa (AN). Database searches of MEDLINE and PsycINFO (from January 1966 to January 2014) were performed, and original articles published as full papers, brief reports, case reports, or case series were included. Forty-one papers were screened in detail, and salient characteristics of pharmacological options for AN were summarized for drug classes. The body of evidence for the efficacy of pharmacotherapy in AN was unsatisfactory, the quality of observations was questionable (eg, the majority were not blinded), and sample size was often small. More trials are needed, while considering that nonresponse and nonremission are typical of patients with AN.

Catatonia in 26 patients with bipolar disorder: clinical features and response to electroconvulsive therapy.

OBJECTIVES: We describe the clinical characteristics and short-term outcomes of a sample of inpatients with bipolar disorder with severe catatonic features resistant to pharmacological treatment. METHODS: The study involved 26 catatonic patients, resistant to a trial of benzodiazepines, and then treated with electroconvulsive therapy (ECT). All patients were evaluated prior to and one week following the ECT course using the Bush-Francis Catatonia Rating Scale (BFCRS) and the Clinical Global Impression (CGI). RESULTS: In our sample, women were over-represented (n = 23, 88.5%), the mean (± standard deviation) age was 49.5 ± 12.5 years, the mean age at onset was 28.1 ± 12.8 years, and the mean number of previous mood episodes was 5.3 ± 2.9. The mean duration of catatonic symptoms was 16.7 ± 11.8 (range: 3-50) weeks, and personal history of previous catatonic episodes was present in 10 patients (38.5%). Seventeen (65.4%) patients showed abnormalities at cerebral computerized tomography and/or magnetic resonance imaging and neurological comorbidities were observed in 15.4% of the sample. Stupor, rigidity, staring, negativism, withdrawal, and mutism were observed in more than 90% of patients. At the end of the ECT course, 21 patients (80.8%) were classified as responders. The BFCRS showed the largest percentage of improvement, with an 82% reduction of the initial score. The number of previous mood episodes was significantly lower and the use of anticholinergic and dopamine-agonist medications was significantly more frequent in non-responders than in responders. CONCLUSIONS: Our patients with bipolar disorder had predominantly retarded catatonia, frequent previous catatonic episodes, indicating a recurrent course, and high rates of concomitant brain structure alterations. However, ECT was a very effective treatment for catatonia in this patient group that was resistant to benzodiazepines.