Autologous chondrocyte implantation for the treatment of osteochondral lesions of the talus: What happens after 20 years?

BACKGROUND: The purpose of this study was to assess the long-term clinical efficacy of first-generation autologous chondrocyte implantation (ACI) technique for osteochondral lesions of the ankle joint. METHODS: Eleven patients with symptomatic OLTs underwent ACI from December 1997 to October 2002. A total of 9 patients (5 men, 4 women, age 25.2 ± 6.3) were evaluated at baseline and at 1, 3, 10 years, and at final follow-up of minimum 20 years with AOFAS ankle-hindfoot score, NRS for pain, and with the Tegner score. RESULTS: The AOFAS score improved significantly from the baseline value of 40.4 ± 19.8 to 82.7 ± 12.9 at the final follow-up (p < 0.0005). The NRS for pain improved significantly from 7.8 ± 0.7 at baseline to 4.8 ± 2.1 at the final follow-up (p < 0.0005). Moreover, the Tegner score underwent a modification from the pre-operative median value of 1 (range: 1-3) and from a pre-injury value of 5 (range: 3-7) to 3 (range: 2-4) at the final follow-up (p < 0.0005). CONCLUSIONS: ACI has proven to be an effective treatment option for patients suffering from OLTs, leading to a long-lasting clinical improvement even beyond 20 years of follow-up. LEVEL OF EVIDENCE: Level IV.

Clozapine Treatment for Aggressive Behaviors in Youths with Neurodevelopmental Disorders.

Objectives: The aim of this study was to assess effectiveness and tolerability of Clozapine in the treatment of aggression in youth with Neurodevelopmental Disorders. Methods: Patients were consecutively admitted at our third-level university hospital with nationwide catchment from June 2018 to October 2022, and followed up to July 2023. Eligibility criteria were as follows: (1) Autism Spectrum Disorder (ASD) and/or Intellectual Disability/Borderline Cognitive Functioning, (2) behavioral dyscontrol with physical aggression; (3) age range between 8 and 18 years; (4) clinical indication for Clozapine treatment after at least two failed trials with other Second-Generation Antipsychotics (SGAs); (5) availability of an at least 6-month-long follow-up. To evaluate the response to Clozapine, we used the Clinical Global Impressions (CGI) rating scales (Clinical Global Impressions-Severity [CGI-S] and Clinical Global Impressions-Improvement [CGI-I]), the Children's Global Assessment Scale (CGAS), and the Aberrant Behavior Checklist (ABC). Results: Twenty-six children and adolescents (21 boys, age 13.47 ± 2.05 years, follow-up duration 9.77 ± 3.50 months) were included in the analysis. Clinical severity (CGI-S) and functional impairment (Clinical Global Assessment Scale) significantly improved, as well as the ABC Total Score and the scores in several subscales. Sixteen patients (61.54%) were responders (CGI-I ≤2), and 13 (50.00%) displayed remission of aberrant behaviors (ΔABC-Total >35), while response/remission condition was not affected by add-on medications and psychotherapy. Most frequent side effects were increased appetite (50.00%), sialorrhea (38.46%), and increased repetitive behaviors (26.92%). Two patients presented epileptic seizures, while no patients presented leucopoenia. Conclusions: Our results suggest that Clozapine may be helpful in ameliorating treatment-resistant aggression in youth with neurodevelopmental conditions. Possible pharmacological strategies for the management of most frequent side effects are also suggested.

Internet Gaming Disorder in Children and Adolescents with Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have been related to an increased risk for behavioral addictions including online gaming. However, the relationship between these two conditions and Internet gaming disorder (IGD) is still debated. The aim of this study is to address this topic by exploring the prevalence of IGD in a consecutive sample of ASD youth and ADHD youth, compared with a normal control group, and by assessing selected psychopathological and neuropsychological features in ASD and ADHD patients with and without IGD. This study included 77 ASD patients (67 males, mean age 13.58 ± 2.75 years), 94 ADHD patients (79 males, mean age 11.46 ± 2.47 years), and 147 normal controls (NC) (mean age 13.9 ± 3.0 years, 114 males) that received structured measures for IGD (IAT, IGDS9-SF, and UADI). In the ADHD group, 72.34% of the sample were above the IGD cut-off, compared with 45.45% in the ASD group and 9.5% in the NC group. ASD patients with IGD presented with greater severity and more severe attention problems, with no difference in the ASD core symptoms between patients with and without IGD. In the comparison between the ASD and ADHD groups according to the presence of IGD, ASD patients with IGD were the most severe group according to the CGI (Clinical Global Impression) scale. The follow-up, conducted on 45 patients affected by ASD, showed an improvement in CGI and CGAS (Children's Global Assessment Scale) scores, but not in the IGD symptoms. These findings could place the diagnosis of ASD as a negative prognostic factor in the follow-up of aspects of video game addiction compared with ADHD.

The 'placebo effect' in the conservative treatment of plantar fasciitis: a systematic review and meta-analyses.

Purpose: The study of the placebo effect is key to elucidate the 'real effect' of conservative interventions for plantar fasciitis. The aim of this meta-analysis was to quantify the impact of placebo in the different conservative treatments of plantar fasciitis. Methods: A systematic literature review was performed on double-blind placebo-controlled trials (RCTs) according to PRISMA guidelines on PubMed, Embase, and Web of Science. The meta-analysis primary outcome was the 0-10 pain variation after placebo treatments analyzed at 1 week, 1, 3, 6, and 12 months. The risk of bias was assessed using the RoB 2.0 tool, while the overall quality of evidence was graded according to the GRADE guidelines. Results: The placebo effect for conservative treatments was studied in 42 double-blind RCTs on 1724 patients. The meta-analysis of VAS pain showed a statistically significant improvement after placebo administration of 2.13/10 points (P < 0.001), being highest at 12 months with 2.79/10 points (P < 0.001). The improvement of the placebo groups was higher in the extracorporeal shock wave therapy studies compared to the injection studies (2.59 vs 1.78; P = 0.05). Eight studies had a low risk of bias, 23 studies had 'some concerns,' and 4 studies had a high risk of bias. The GRADE evaluation showed an overall high quality of evidence. Conclusion: This systematic review and meta-analysis demonstrated that the placebo effect represents an important component of all conservative approaches to treat plantar fasciitis. This effect is statistically and clinically significant, increases over time, and depends on the type of conservative treatment applied to address plantar fasciitis.

Hikikomori (Severe Social Withdrawal) in Italian Adolescents: Clinical Features and Follow-Up.

Severe social withdrawal, including staying alone in one's bedroom, non-attendance at school or work, and minimal or absent social contacts, sometimes only through electronic devices, can be found in several psychiatric disorders, or in a 'primary' form, firstly defined in Japan as 'Hikikomori'. The distinction between primary and secondary forms is questionable, as it prevalently depends on the quality of psychiatric assessment. To date, few studies specifically explored Hikikomori in an adolescent population outside Japan. The aim of the present study is to describe clinical features of a consecutive group of 80 referred youth (13 to 18 years, 57 males) with social isolation, of which 40 were followed up on for 4-6 months, to characterize clinical features and outcome. All the participants presented psychiatric comorbid disorders, prevalently anxiety disorders, mood disorders, and autism spectrum disorder. Suicidality (ideation and behavior) was reported in 32.5% of the participants, and 20% of the participants attempted suicide. More than half of the participants exceeded the cut-off of the Internet Addiction Test, and 42.4% met the criteria for the Internet Gaming Disorder. At the follow-up appointment, an improvement of social withdrawal was reported in 75% of the sample; 67.5% of the participants significantly improved according to the CGI-improvement scale; and 55% of the participants had an improvement of functioning according to the C-GAS. Our findings suggest that Hikikomori is a transnosographic entity, with high rates of suicidality and Internet addiction, and that can it improve when it is timely diagnosed and treated.

Hyaluronic scaffold transplantation with bone marrow concentrate for the treatment of osteochondral lesions of the talus: durable results up to a minimum of 10 years.

PURPOSE: The aim of this study was to evaluate the long-term clinical results of the transplantation of a hyaluronic acid membrane augmented with bone marrow aspirate concentrate (BMAC) in an one-step technique for the treatment of patients affected by osteochondral lesions of the talus (OLT). METHODS: A total of 101 patients (64 men, 37 women, age 32.9 ± 10.9) were evaluated for a minimum of 10 years of follow-up (151.5 ± 18.4 months) The mean lesion size was 2.2 ± 1.4 cm2, the lesion had a post-traumatic origin in 73 patients, 15 patients previously had an ankle fracture, 22 patients had ankle osteoarthritis. All patients were clinically evaluated at baseline and at 2, 5, and a minimum of 10 years after treatment using the AOFAS score, the NRS for pain, and the Tegner score. A survival analysis was performed to check the survival to failure up to the last follow-up. RESULTS: The AOFAS score significantly improved from baseline (59.6 ± 13.9) to the final follow-up (82.3 ± 14.2) (p < 0.0005). A significant reduction in the AOFAS score was found from 2 to 10 years (p < 0.0005). The NRS for pain changed from 7.0 ± 1.3 at baseline to 3.9 ± 2.7 at the final follow-up (p < 0.0005). A significant worsening was documented between 5 years and the final follow-up (p < 0.0005). The Tegner score improved from the preoperative value of 2.0 (range 1-7) to 3.0 (range 1-7) at the final follow-up (p < 0.0005), although it remained lower as compared to the preinjury level of 4.0 (range 1-9) (p < 0.0005). Better results were documented in male and younger patients with smaller lesions, without the previous surgery, and without the previous ankle fractures or osteoarthritis. At the final follow-up, 85 patients considered their general health status "satisfactory" and 84 patients reported feeling "better" than the preoperative condition. Five patients were considered failures and underwent prosthetic ankle replacement or repeated the same surgery. CONCLUSION: This one-step technique showed to be an effective procedure for the treatment of OLT, providing a low failure rate and offering durable clinical improvements up to a minimum of 10 years of follow-up. However, this technique demonstrated a small yet significant decrease over the years in terms of pain and function and poor results in terms of sports activity level. LEVEL OF EVIDENCE: Level IV.

Subtalar arthroereisis post-operative management in children: A literature review.

PURPOSE: Subtalar arthroereisis is a minimally-invasive technique for the treatment of flexible flatfoot. Some issues regarding the procedure are still debated, such as post-operative management. The aim of this study is to offer a review of the pertaining literature to identify current post-operative protocols and describe possible differences among them. METHODS: We searched the PubMed database for all papers related to subtalar arthroereisis in children specifying the post-operative protocols. After reviewing all studies according to excluding criteria, 50 articles were selected for analysis. RESULTS: Based on the literature review, different post-operative protocols emerged in the treatment of patients undergoing subtalar arthroereisis, in particular regarding length of hospital stay, type and duration of immobilization, weight-bearing management, adopted rehabilitation scheme, sport resumption and implant removal. CONCLUSIONS: The most important finding was the existence of a wide variety in post-operative management after subtalar arthroereisis in children, thus confirming that no clear consensus still exists in this field.

Persistent Non-Suicidal Self-Injury and Suicidality in Referred Adolescents: A Longitudinal Study Exploring the Role of Cyclothymic Temperament.

Non-suicidal self-injury (NSSI) is deliberate harm to the body surface without suicidal intent, though it may be a predictor of suicide attempts. Our aim was to test the hypothesis that persisting and recovering NSSI may have a different longitudinal risk for suicidal ideation and behavior and that the intensity of Cyclothymic Hypersensitive Temperament (CHT) may increase this risk. Fifty-five patients (mean age 14.64 ± 1.77 years) referred for mood disorders according to the DSM-5 were consecutively recruited and followed-up for a mean of 19.79 ± 11.67 months and grouped according to the presence/absence of NSSI at baseline and follow-up into three groups: without NSSI (non-NSSI; n = 22), with NSSI recovered at follow-up (past-NSSI; n = 19), and with persistent NSSI at follow-up (pers-NSSI; n = 14). At follow-up, both NSSI groups were more severely impaired and failed to improve internalizing problems and dysregulation symptoms. Both NSSI groups reported higher scores in suicidal ideation compared to non-NSSI, but only pers-NSSI presented higher scores in suicidal behavior. CHT was higher in pers-NSSI, followed by past-NSSI and then by non-NSSI. Our data support a continuity between NSSI and suicidality, and they suggest the prognostic validity of persistent NSSI, associated with highest CHT scores.

Early Sensory Profile in Autism Spectrum Disorders Predicts Emotional and Behavioral Issues.

Background: Abnormal sensory reactivity is considered one of the diagnostic criteria for autism spectrum disorders (ASD) and has been associated with autism severity, poorer functional outcomes, and behavioral difficulties across the lifespan. Its early characterization could provide valuable insights into the processes favoring the instantiation of maladaptive behaviors. Objectives: The present study has two aims: (1) to describe the sensory profile of preschool children with ASD compared with an age-matched population of children with a diagnosis of language disorder (DLD) and typically developing (TD) control peers; (2) to explore within each group whether the sensory alterations play a predictive role in the instantiation of emotional and behavioral issues. Methods: The parents of 42 ASD, 18 DLD, and 56 TD filled out the Sensory Processing Measure­Preschool (SPM-P). To gather information on competencies, behaviors, and emotional problems of children, the Child Behavior Checklist 1½-5 (CBCL 1½-5) was also administered. Results: On the SPM-P, ASD and DLD samples generally had scores more compromised than control peers. The contrast between ASD and DLD was reflected in a higher (and highly significant) impairment on the social participation and hearing subscales, suggesting a greater sensitivity and a possible specificity of these scores for ASD. More importantly, linear regression analyses revealed a strong and predictive association for ASD children with SPM total scores explaining more than 50% of the variance of the CBCL 1½-5 total scores (p < 0.001). Conclusions: Our findings reinforce the need to detect the abnormal sensory profiles of ASD already at an early stage and during clinical evaluations. Due to the impact on the emotional and behavioral manifestations, such a procedure has significant clinical and social implications, potentially guiding the development of new interventions relying on multisensory strategies.

Patient-specific instrumentation in total ankle arthroplasty.

The recent increase in the adoption of total ankle arthroplasty (TAA) reflects the improvements in implant designs and surgical techniques, including the use of preoperative navigation system and patient-specific instrumentation (PSI), such as custom-made cutting guides. Cutting guides are customized with respect to each patient's anatomy based on preoperative ankle computed tomography scans, and they drive the saw intra-operatively to improve the accuracy of bone resection and implant positioning. Despite some promising results, the main queries in the literature are whether PSI improves the reliability of achieving neutral ankle alignment and more accurate implant sizing, whether it is actually superior over standard techniques, and whether it is cost effective. Moreover, the advantages of PSI in clinical outcomes are still theoretical because the current literature does not allow to confirm its superiority. The purpose of this review article is therefore to assess the current literature on PSI in TAA with regard to current implants with PSI, templating and preoperative planning strategies, alignment and sizing, clinical outcomes, cost analysis, and comparison with standard techniques.

Sensory Profiles in School-Aged Children with Autism Spectrum Disorder: A Descriptive Study Using the Sensory Processing Measure-2 (SPM-2).

Background: Sensory reactivity is considered one of the diagnostic criteria for Autism Spectrum Disorders (ASD) and has been associated with poorer functional outcomes, behavioral difficulties, and autism severity across the lifespan. The characterization of the sensory processing in ASD has thus become crucial to identify the sensory and motor features influencing the development of personal autonomy. Objectives: The present study has two aims: (1) to compare the sensory processing between school-aged children with ASD and typically developing peers (TD); (2) to evaluate whether, within the ASD sample, the cognitive level and reported sensory symptoms explain the scores exhibited at the Sensory Processing Measure (SPM-2). Methods: The SPM-2 test was administered to the parents of 105 children with ASD and 70 TD. The ASD group was further subdivided into two groups, namely high and low functioning based on their cognitive level (High Functioning (HF), IQ > 80; Low Functioning (LF), IQ < 80). Results: ASD children exhibited higher scores throughout the SPM-2 total score and its multiple subscales. Within ASD, while HF and LF children did not differ in terms of the SPM-2 total score, a significant difference was found for the hearing, social participation, and balance and motion subscales. Conclusions: Aside from classical knowledge that the ASD population suffers from sensory processing disorders, we revealed that different sensory patterns are associated with high or low cognitive functioning. Beyond its neurobiological interest, such knowledge may be of fundamental importance for individualizing psychoeducational interventions in preschool- and school-aged children and later developmental stages.

Could You Give Me the Blue Brick? LEGO®-Based Therapy as a Social Development Program for Children with Autism Spectrum Disorder: A Systematic Review.

LEGO®-based therapy is a social skills development program aimed at children with autism spectrum disorder (ASD). A systematic review of the literature was conducted using PRISMA guidelines. PubMed, Scopus and Web of Science bibliographic databases were searched from their date of inception to August 2020. The review included 19 studies. Studies were classified according to experimental designs (e.g., Randomized Control Trial, Non-Randomized Studies of Interventions and case report and series) and a narrative synthesis of each was provided, along with a critical discussion of the strengths and weaknesses of the available literature on the topic. Although LEGO®-based therapy appears a promising treatment for social interaction in ASD, the findings of LEGO®-based therapy studies should be interpreted and generalized with caution, due to the low quality of the studies and the small sample sizes.

Traumatic Cuboid Dislocation. The Potential Role of Plantar Ligaments Integrity in Facilitating Reduction: A Case Report.

CASE: A 56-year-old male patient sustained a traumatic cuboid medioplantar dislocation associated with a lateral cuneiform fracture. The patient was treated with open reduction and fixation using 2 temporary Kirschner wires. During surgery, the plantar ligament apparatus was found to be almost intact and the reduction was easily performed. At the last follow-up visit, the patient's functional outcomes were excellent. CONCLUSIONS: Traumatic cuboid medioplantar dislocation associated with lateral cuneiform fracture usually requires surgical treatment. The authors conclude the integrity of the plantar ligament apparatus may play a role in facilitating the reduction.

A novel multidimensional questionnaire for the assessment of emotional dysregulation in adolescents: Reactivity, Intensity, Polarity and Stability questionnaire-youth version (RIPoSt-Y).

BACKGROUND: The failure to regulate emotions, namely emotional dysregulation (ED), is a relevant construct in adolescent psychiatry, in terms of prognostic and developmental implications. We developed and validated a novel self-report questionnaire for the assessment of ED, the RIPoSt-Y, both in clinical and non-clinical samples. METHODS: Items selection and subscales construction were conducted on healthy controls (n=374), while test-retest reliability was evaluated in a subsample (n=72); internal consistency was examined both in the control group and in two clinical samples, respectively including patients with Bipolar Spectrum Disorders (BSD; n=44) and ADHD (n=34). Construct, concurrent and convergent validity were also assessed. RESULTS: Thirty-one items were finally retained, and three subscales were identified (Affective Instability, Emotional Reactivity, Interpersonal Sensitivity). Test-retest was significant for each subscale with moderate-to-good correlations, and internal consistency showed good-to-excellent coefficients. Construct validity was supported by significant differences between patients and controls and gender-related differences. Concurrent validity was confirmed through significant associations with two subscales of the CHT-Q, while convergent validity proved to be significant with the CBCL/YSR dysregulation-profile. Cut-offs were also computed to discriminate clinically significant scores of ED. LIMITATIONS: The use of a school-based survey to recruit controls could have biased our results; gender distributions between clinical and non-clinical samples were significantly different. CONCLUSIONS: Our novel questionnaire proved to be a valid and reliable tool able to assess the presence of ED in youths and to characterize this fundamental construct in its multidimensional facets.

Autism Spectrum Disorder and Disruptive Behavior Disorders Comorbidities Delineate Clinical Phenotypes in Attention-Deficit Hyperactivity Disorder: Novel Insights from the Assessment of Psychopathological and Neuropsychological Profiles.

Although childhood-onset psychiatric disorders are often considered as distinct and separate from each other, they frequently co-occur, with partial overlapping symptomatology. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) commonly co-occur with each other and with other mental disorders, particularly disruptive behavior disorders, oppositional defiant disorder/conduct disorder (ODD/CD). Whether these associated comorbidities represent a spectrum of distinct clinical phenotypes is matter of research. The aim of our study was to describe the clinical phenotypes of youths with ADHD with and without ASD and/or ODD/CD, based on neuropsychological and psychopathological variables. One-hundred fifty-one participants with ADHD were prospectively recruited and assigned to four clinical groups, and assessed by means of parent-reported questionnaires, the child behavior checklist and the behavior rating inventory of executive functions. The ADHD alone group presented a greater impairment in metacognitive executive functions, ADHD+ASD patients presented higher internalizing problems and deficits in Shifting tasks, and ADHD+ODD/CD subjects presented emotional-behavioral dysregulation. Moreover, ADHD+ASD+ODD/CD individuals exhibited greater internalizing and externalizing problems, and specific neuropsychological impairments in the domains of emotional regulation. Our study supports the need to implement the evaluation of the psychopathological and neuropsychological functioning profiles, and to characterize specific endophenotypes for a finely customized establishment of treatment strategies.

A Naturalistic Study of Youth Referred to a Tertiary Care Facility for Acute Hypomanic or Manic Episode.

BACKGROUND: Bipolar Disorders (BD) in youth are a heterogeneous condition with different phenomenology, patterns of comorbidity and outcomes. Our aim was to explore the effects of gender; age at onset (prepubertal- vs. adolescent-onset) of BD; and elements associated with attention deficit hyperactivity disorder (ADHD) and Substance Use Disorder (SUD) comorbidities, severe suicidal ideation or attempts, and poorer response to pharmacological treatments. METHOD: 117 youth (69 males and 57 females, age range 7 to 18 years, mean age 14.5 ± 2.6 years) consecutively referred for (hypo)manic episodes according to the Diagnostic and Statistical Manual of Mental Disorders, 54th ed (DSM 5) were included. RESULTS: Gender differences were not evident for any of the selected features. Prepubertal-onset BD was associated with higher rates of ADHD and externalizing disorders. SUD was higher in adolescent-onset BD and was associated with externalizing comorbidities and lower response to treatments. None of the selected measures differentiated patients with or without suicidality. At a 6-month follow up, 51.3% of the patients were responders to treatments, without difference between those receiving and not receiving a psychotherapy. Clinical severity at baseline and comorbidity with Conduct Disorder (CD) and SUD were associated with poorer response. Logistic regression indicated that baseline severity and number of externalizing disorders were associated with a poorer outcome. CONCLUSIONS: Disentangling broader clinical conditions in more specific phenotypes can help timely and focused preventative and therapeutic interventions.

Lithium treatment in bipolar adolescents: a follow-up naturalistic study.

BACKGROUND: Although lithium is currently approved for the treatment of bipolar disorders in youth, long term data, are still scant. The aim of this study was to describe the safety and efficacy of lithium in referred bipolar adolescents, who were followed up at the 4th (T1) and 8th (T2) month of treatment. METHODS: The design was naturalistic and retrospective, based on a clinical database, including 30 patients (18 males, mean age 14.2±2.1 years). RESULTS: Mean blood level of lithium was 0.69±0.20 mEq/L at T1 and 0.70±0.18 mEq/L at T2. Both Clinical Global Impression-Severity (CGI-S) and Children Global Assessment Scale (C-GAS) scores improved from baseline (CGI-S 5.7±0.5, C-GAS 35.1±3.7) to T1 (CGI-S 4.2±0.70, C-GAS 46.4±6.5; P<0.001), without significant differences from T1 to T2. Thyroid-stimulating hormone significantly increased from 2.16±1.8 mU/mL at baseline to 3.9±2.7 mU/mL at T2, remaining within the normal range, without changes in T3/T4 levels; two patients needed a thyroid hormone supplementation. Creatinine blood level did not change. No cardiac symptoms and electrocardiogram QTc changes occurred. White blood cell count significantly increased from 6.93±1.68 103/mmc at baseline to 7.94±1.94 103/mmc at T2, and serum calcium significantly increased from 9.68±0.3 mg/dL at baseline to 9.97±0.29 mg/dL at T2, both remaining within the normal range; all the other electrolyte levels were stable and normal during the follow-up. The treatment with lithium was well tolerated, probably due to the relatively low lithium blood levels. Gastrointestinal symptoms (16.7%), sedation (9.7%) and tremor (6.4%) were the most frequently reported side effects. CONCLUSION: Lithium was effective and safe in adolescent bipolar patients followed-up for eight months.

Massive asymptomatic creatine kinase elevation in youth during antipsychotic drug treatment: case reports and critical review of the literature.

A massive asymptomatic creatine kinase elevation (MACKE) has been described during antipsychotic exposure in adult psychotic patients without signs of neuroleptic malignant syndrome (NMS), or other most frequent reasons for high creatine kinase (CK) serum level (intramuscular injections, restraints, intense physical activity, dystonic reactions). In this article, we review this clinical condition, and report three cases of MACKE in nonpsychotic, drug-naïve youth during treatment with second generation antipsychotics. The diagnosis of MACKE should be considered after ruling out other possible common reasons of CK increase. The finding of MACKE should indicate a need for weekly monitoring of the CK level only when there are reasons to believe elevated CK is toxic or harmful. Further investigations are recommended when signs and symptoms raise a suspicion of NMS or rhabdomyolysis, including flu-like syndrome, fever, weakness, alteration of consciousness, muscle rigidity, tachycardia, hyper-/hypotension, and dark urine. A drug discontinuation should be considered when possible signs of NMS or rhabdomyolysis are suspected, or in cases of very high and persisting CK levels. Empirical evidence indicates that there is not a "safe" antipsychotic medication; therefore, a switch to another antipsychotic with a different profile is not necessarily a safe option. The spontaneously remitting or intermittent course suggests that the "true" MACKE should be kept distinct from both rhabdomyolysis and NMS. Raising awareness with MACKE may reduce the need for unnecessary diagnosis of NMS or rhabdomyolysis, which may otherwise lead to an unnecessary discontinuation of an effective therapeutic agent.

Denial of symptoms and psychopathology in adolescent anorexia nervosa.

OBJECTIVE: To evaluate the psychopathological status and denial of symptoms in a sample of 38 consecutively admitted adolescents with anorexia nervosa (AN). METHOD: The Schedule for Affective Disorders and Schizophrenia for School-Aged Children was used to determine the categorical diagnosis of eating disorder. The anorexic adolescents completed the EAT-40 (Eating Attitude Test) and, on the basis of its score, the sample was dichotomized in a false-negative group (FNG) scoring under 30 and a positive group (PG) scoring over 30. We compared these two subgroups in terms of clinical variables (age of onset and admission, duration of illness prior to admission, diagnosis, BMI) and psychopathology assessed by the CBCL (Child Behaviour Checklist) and the YSR (Youth Self-Report). In order to evaluate the possible role of diagnosis and BMI on the EAT score we also dichotomized the sample with respect to the diagnosis (full vs. partial AN) and to the mean female BMI (< or = 15 vs. > 15). RESULTS: A significant difference was found in terms of duration of illness prior to admission, which was briefer in the FNG. Higher CBCL and YSR values were found in the PG with significant differences in terms of YSR internalizing symptoms. A large amount of significantly positive Pearson's correlations were found between the CBCL and YSR values in the FNG. No significant Pearson's correlations were found between EAT, BMI and diagnosis. CONCLUSIONS: The lower CBCL and YSR values in the FNG seem to point out a tendency of this group to deny anxiety and depression as well as an eating pathology; the longer duration of illness prior to admission in the PG seems to support the hypothesis that the PG may be considered to be not so much more disturbed as more aware of its eating attitudes and psychopathology. The nature of denial in anorexic adolescents is discussed.

Internalizing and externalizing conditions in adolescent anorexia.

OBJECTIVE: To identify the prevalence of internalizing and externalizing conditions in referred anorexic adolescents. METHOD: Child Behavior CheckList (CBCL) and Youth Self Report (YSR) were used to assess psychopathology: (a) in the global sample (43 adolescents); (b) in different subtypes of anorexia; (c) considering the timing of admission after the onset of the disease. RESULTS: A high percentage of patients were found in the internalizing clinical range both at CBCL and YSR. Higher mean values were found in full syndromes both at CBCL and YSR, and in the binge-eating subtype only at the YSR. Subjects arrived within the first year of illness showed a less severe psychopathology. CONCLUSIONS: Adolescents with anorexia have high rates of internalizing psychopathology. The less severe psychopathology in adolescents arrived within the first year of illness shed light on discontinuity between anorexia and internalizing condition. On the basis of the psychopathological severity, three types of adolescent anorexia are proposed which could be of interest for therapeutic decisions.