Untangling adaptive functioning of PMM2-CDG across age and its impact on parental stress: a cross-sectional study.

Phosphomannomutase deficiency (PMM2-CDG) leads to cerebellar atrophy with ataxia, dysmetria, and intellectual deficits. Despite advances in therapy, the cognitive and adaptive profile remains unknown. Our study explores the adaptive profile of 37 PMM2-CDG patients, examining its association with parental stress and medical characteristics. Assessment tools included ICARS for the cerebellar syndrome and NPCRS for global disease severity. Behavioral and adaptive evaluation consisted of the Vineland Adaptive Behavior Scale and the Health of the Nation Outcome Scales. Psychopathological screening involved the Child Behavior Checklist and the Symptom Check-List-90-R. Parental stress was evaluated using Parental Stress Index. Results were correlated with clinical features. No significant age or sex differences were found. 'Daily living skills' were notably affected. Patients severely affected exhibited lower adaptive skill values, as did those with lipodystrophy and inverted nipples. Greater severity in motor cerebellar syndrome, behavioral disturbances and the presence of comorbidities such as hyperactivity, autistic features and moderate-to-severe intellectual disability correlated with greater parental stress. Our study found no decline in adaptive abilities. We provide tools to assess adaptive deficits in PMM2-CDG patients, emphasizing the importance of addressing communication, daily living skills, and autonomy, and their impact on parental stress in clinical monitoring and future therapies.

Ethical Challenges of Early Identification of Advanced Chronic Patients in Need of Palliative Care: The Catalan Experience.

Palliative care must be early applied to all types of advanced chronic and life limited prognosis patients, present in all health and social services. Patients' early identification and registry allows introducing palliative care gradually concomitant with other measures. Patients undergo a systematic and integrated care process, meant to improve their life quality, which includes multidimensional assessment of their needs, recognition of their values and preferences for advance care planning purposes, treatments review, family care, and case management. Leaded by the National Department of Health, a program for the early identification of these patients has been implemented in Catalonia (Spain). Although the overall benefits expected, the program has raised some ethical issues. In order to address these challenges, diverse institutions, including bioethics and ethics committees, have elaborated a proposal for the program's advantages. This paper describes the process of evaluation, elaboration of recommendations, and actions done in Catalonia.

[Empathy, inter-professional collaboration, and lifelong medical learning in Spanish and Latin-American physicians-in-training who start their postgraduate training in hospitals in Spain. Preliminary outcomes]. / Empatía, habilidades de colaboración interprofesional y aprendizaje médico permanente en residentes españoles y latinoamericanos que inician los programas de formación médica especializada en España. Resultados preliminares.

OBJECTIVE: To identify similarities and differences in empathy, abilities toward inter-professional collaboration, and lifelong medical learning, between Spanish and Latin-American physicians-in-training who start their posgraduate training in teaching hospitals in Spain. DESIGN: Observational study using self-administered questionnaires. SETTINGS: Five teaching hospitals in the province of Barcelona, Spain. PARTICIPANTS: Spanish and Latin-American physicians-in-training who started their first year of post-graduate medical training. MAIN MEASUREMENTS: Empathy was measured using the Jefferson scale of empathy. Abilities for inter-professional collaboration were measured using the Jefferson scale attitudes towards nurse-physician collaboration. Learning was measured using the Jefferson scale of medical lifelong learning scale. RESULTS: From a sample of 156 physicians-in-training, 110 from Spain and 40 from Latin America, the Spanish group showed the highest empathy (p<.05). On the other hand, Latin-American physicians had the highest scores in lifelong learning abilities (p<.001). A positive relationship was found between empathy and inter-professional collaboration for the whole sample (r=+0.34; p<.05). CONCLUSIONS: These results confirm previous preliminary data and underline the positive influence of empathy in the development of inter-professional collaboration abilities. In Latin-American physicians who start posgraduate training programs, lifelong learning abilities have a positive influence on the development of other professional competencies.

Phosphomannomutase deficiency (PMM2-CDG): ataxia and cerebellar assessment.

BACKGROUND: Phosphomannomutase deficiency (PMM2-CDG) is the most frequent congenital disorder of glycosylation. The cerebellum is nearly always affected in PMM2-CDG patients, a cerebellar atrophy progression is observed, and cerebellar dysfunction is their main daily functional limitation. Different therapeutic agents are under development, and clinical evaluation of drug candidates will require a standardized score of cerebellar dysfunction. We aim to assess the validity of the International Cooperative Ataxia Rating Scale (ICARS) in children and adolescents with genetically confirmed PMM2-CDG deficiency. We compare ICARS results with the Nijmegen Pediatric CDG Rating Scale (NPCRS), neuroimaging, intelligence quotient (IQ) and molecular data. METHODS: Our observational study included 13 PMM2-CDG patients and 21 control subjects. Ethical permissions and informed consents were obtained. Three independent child neurologists rated PMM2-CDG patients and control subjects using the ICARS. A single clinician administered the NPCRS. All patients underwent brain MRI, and the relative diameter of the midsagittal vermis was measured. Psychometric evaluations were available in six patients. The Mann-Whitney U test was used to compare ICARS between patients and controls. To evaluate inter-observer agreement in patients' ICARS ratings, intraclass correlation coefficients (ICC) were calculated. ICARS internal consistency was evaluated using Cronbach's alpha. Spearman's rank correlation coefficient test was used to correlate ICARS with NPCRS, midsagittal vermis relative diameter and IQ. RESULTS: ICARS and ICARS subscores differed between patients and controls (p < 0.001). Interobserver agreement of ICARS was "almost perfect" (ICC = 0.99), with a "good" internal reliability (Cronbach's alpha = 0.72). ICARS was significantly correlated with the total NPCRS score (rs 0.90, p < 0.001). However, there was no agreement regarding categories of severity. Regarding neuroimaging, inverse correlations between ICARS and midsagittal vermis relative diameter (rs -0.85, p = 0.003) and IQ (rs -0.94, p = 0.005) were found. Patients bearing p.E93A, p.C241S or p.R162W mutations presented a milder phenotype. CONCLUSIONS: ICARS is a reliable instrument for assessment of PMM2-CDG patients, without significant inter-rater variability. Despite our limited sample size, the results show a good correlation between functional cerebellar assessment, IQ and neuroimaging. For the first a correlation between ICARS, neuroimaging and IQ in PMM2-CDG patients has been demonstrated.

Laser evoked potentials and prepulse inhibition of the blink reflex in patients with Wallenberg's syndrome.

Spinothalamic tract lesions in patients with Wallenberg's syndrome can be demonstrated by abnormalities in the laser evoked potentials (LEPs) to stimulation of the affected side. However, before reaching the structures generating LEPs, laser stimuli can induce effects at a subcortical level. We examined LEPs and laser-induced prepulse inhibition of the blink reflex in seven patients with Wallenberg's syndrome within a month after the infarct. All patients had abnormally elevated thresholds for temperature and pain sensation, and for pinprick pain induced by laser stimuli, in the affected vs the non-affected side. LEPs to stimulation of the affected side were abnormal because of absent, reduced or delayed responses. However, the same laser stimuli that were unable to induce LEPs generated normal inhibition of the blink reflex response when applied 250ms before a trigeminal nerve electrical stimulus. The percentage inhibition induced in the R2 response of the blink reflex by laser stimulation of the affected side was not different from that induced by stimulation of the non-affected side, or in control subjects. These results are compatible with either a different pathway for prepulse inhibition and evoked potentials or a reduced energy requirement of the sensory input generating prepulse inhibition in comparison to that generating evoked potentials.