Patient's punctuality in an outpatient clinic: the role of age, medical branch and geographical factors.

BACKGROUND: The efficiency of the management of an outpatient clinic largely depends on the administration of patient flows and waiting times increase costs and affect clinical quality. In this study, we verify if the visit acceptance times are influenced by demographic or geographical factors in a large cohort of patients referred to a city and suburban private outpatient multidisciplinary clinic. METHODS: We included all scheduled visits of patients aged from 18 to 75 years who arrived in 2021, 2022 and 2023 in our private outpatient clinics, consisting of 34 medical clinics scattered in Milan metropolitan city and hinterland. The variables collected were age, visit time, check-in time, address of the medical clinic and its distance from the closest underground station, patient typology (new business vs. follow-up patient), and the medical branch of the visit. Outcome is'punctuality', defined as check-in time minus visit time (in minutes). RESULTS: We considered a sample of 410.808 visits from January 2021 to April 2023. The majority of patients check-in early (84.4%) and we found that the percentage of punctual patients increases linearly with age. Earlier hours in the morning show the worst punctuality pattern as well as Blood Draws in the analysis of different medical branches. We also observed that patients who already had some activity recorded in our systems show the worst pattern of punctuality. No particular differences emerged considering the geographical location of the clinics. CONCLUSIONS: Younger patients have worse punctuality than older patients. Moreover, earlier hour slots are the most disadvantaged and the medical specialty has an influence on the arrival habits. This data should be considered for better clinical quality and efficiency.

Distribution of Exonic Variants in Glycogen Synthesis and Catabolism Genes in Late Onset Pompe Disease (LOPD).

Pompe disease (PD) is a monogenic autosomal recessive disorder caused by biallelic pathogenic variants of the GAA gene encoding lysosomal alpha-glucosidase; its loss causes glycogen storage in lysosomes, mainly in the muscular tissue. The genotype-phenotype correlation has been extensively discussed, and caution is recommended when interpreting the clinical significance of any mutation in a single patient. As there is no evidence that environmental factors can modulate the phenotype, the observed clinical variability in PD suggests that genetic variants other than pathogenic GAA mutations influence the mechanisms of muscle damage/repair and the overall clinical picture. Genes encoding proteins involved in glycogen synthesis and catabolism may represent excellent candidates as phenotypic modifiers of PD. The genes analyzed for glycogen synthesis included UGP2, glycogenin (GYG1-muscle, GYG2, and other tissues), glycogen synthase (GYS1-muscle and GYS2-liver), GBE1, EPM2A, NHLRC1, GSK3A, and GSK3B. The only enzyme involved in glycogen catabolism in lysosomes is α-glucosidase, which is encoded by GAA, while two cytoplasmic enzymes, phosphorylase (PYGB-brain, PGL-liver, and PYGM-muscle) and glycogen debranching (AGL) are needed to obtain glucose 1-phosphate or free glucose. Here, we report the potentially relevant variants in genes related to glycogen synthesis and catabolism, identified by whole exome sequencing in a group of 30 patients with late-onset Pompe disease (LOPD). In our exploratory analysis, we observed a reduced number of variants in the genes expressed in muscles versus the genes expressed in other tissues, but we did not find a single variant that strongly affected the phenotype. From our work, it also appears that the current clinical scores used in LOPD do not describe muscle impairment with enough qualitative/quantitative details to correlate it with genes that, even with a slightly reduced function due to genetic variants, impact the phenotype.

The Use of Social Media and Digital Devices Among Italian Neurologists.

Background: Digital devices and online social networks are changing clinical practice. In this study, we explored attitudes, awareness, opinions, and experiences of neurologists toward social media and digital devices. Methods: Each member of the Italian Society of Neurology (SIN) participated in an online survey (January to May 2018) to collect information on their attitude toward digital health. Results: Four hundred and five neurologists participated in the study. At work, 95% of responders use the personal computer, 87% the smartphone, and 43.5% the tablet. These devices are used to obtain health information (91%), maintain contact with colleagues (71%), provide clinical information (59%), and receive updates (67%). Most participants (56%) use social media to communicate with patients, although 65% are against a friendship with them on social media. Most participants interact with patients on social media outside working hours (65.2%) and think that social media have improved (38.0%) or greatly improved (25.4%) the relationship with patients. Most responders (66.7%) have no wearable devices available in clinical practice. Conclusion: Italian neurologists have different practices and views regarding the doctor-patient relationship in social media. The availability of digital devices in daily practice is limited. The use of social networks and digital devices will increasingly permeate into everyday life, bringing a new dimension to health care. The danger is that advancement will not go hand in hand with a legal and cultural adaptation, thus creating ambiguity and risks for clinicians and patients. Neurologists will need to be able to face the opportunities and challenges of this new scenario.

MYH2 myopathy, a new case expands the clinical and pathological spectrum of the recessive form.

BACKGROUND: Hereditary myosin myopathies are a group of rare muscle disorders, caused by mutations in genes encoding for skeletal myosin heavy chains (MyHCs). MyHCIIa is encoded by MYH2 and is expressed in fast type 2A and 2B muscle fibers. MYH2 mutations are responsible for an autosomal dominant (AD) progressive myopathy, characterized by the presence of rimmed vacuoles and by a reduction in the number and size of type 2A fibers, and a recessive early onset myopathy characterized by complete loss of type 2A fibers. Recently, a patient with a homozygous mutation but presenting a dominant phenotype has been reported. METHODS: The patient was examined thoroughly and two muscle biopsies were performed through the years. NGS followed by confirmation in Sanger sequencing was used to identify the genetic cause. RESULTS: We describe the second case presenting with late-onset ophthalmoparesis, ptosis, diffuse muscle weakness, and histopathological features typical for AD forms but with a recessive MYH2 genotype. CONCLUSION: This report contributes to expand the clinical and genetic spectrum of MYH2 myopathies and to increase the awareness of these very rare diseases.

Assessing the Role of Anti rh-GAA in Modulating Response to ERT in a Late-Onset Pompe Disease Cohort from the Italian GSDII Study Group.

INTRODUCTION: Patients with late-onset Pompe disease (LOPD) receiving enzyme replacement therapy (ERT) may develop IgG antibodies against alglucosidase alpha (anti-rhGAA) in the first 3 months of treatment. The exact role of these antibodies in modulating efficacy of ERT in this group of patients is still not fully understood. To assess whether anti rh-GAA antibodies interfere with ERT efficacy, we studied a large Italian cohort of LOPD patients. METHODS: We analyzed clinical findings and performed serial measurements of IgG anti rh-GAA antibody titers from 64 LOPD patients treated with ERT. The first examination (T0) was completed on average at 17.56 months after starting ERT, while the follow-up (T1) was collected on average at 38.5 months. Differences in T0-T1 delta of the six-minute walking test (6MWT), MRC sum score (MRC), gait, stairs and chair performance (GSGC) and forced vital capacity (FVC) were considered and then related to the antibody titers. RESULTS: Almost 22% of the patients never developed antibodies against GAA, while 78.1% had a positive titer (31.2% patients developed a low titer, 43.8% a medium titer and 3.1% a high titer). No statistical significance was found in relating the T0-T1 delta differences and antibody titers, except for MRC sum score values in a subgroup of patients treated < 36 months, in which those with a null antibody titer showed a greater clinical improvement than patients with a positive titer. CONCLUSION: Our results confirm that in a large cohort of LOPD patients, anti rh-GAA antibody generation did not significantly affect either clinical outcome or ERT efficacy. However, in the first 36 months of treatment, a possible interference of low-medium antibody titers with the clinical status could be present. Therefore, a careful and regular evaluation of antibody titers, especially in cases with evidence of clinical decline despite ERT, should be performed.

Immune-mediated necrotizing myopathy due to statins exposure.

Statin-induced necrotizing autoimmune myopathy (IMNM) is an autoimmune disorder induced by anti-3-hydroxy-3-methylglutaryl-coenzyme-A reductase (anti-HMGCR) antibodies. We performed a retrospective clinical, histological, and radiological evaluation of 5 patients with a 3-year therapeutic follow-up. All patients used statins and then experienced proximal weakness that persisted after drug cessation. Muscle biopsies revealed a primary necrotizing myopathy without inflammatory infiltrates. All patients required immunomodulant combination therapy to achieve clinical remission. Magnetic resonance imaging (MRI) showed the presence of edema in the medial gastrocnemius, posterior and central loggia of the thigh, posterior loggia of the arm, and the infraspinatus and subscapularis muscles, as well as extensive inflammation of the subcutaneous tissues and muscolaris fasciae. Serum analysis, muscle biopsy, and MRI are fundamental for IMNM diagnosis and follow-up. The growing use of statins in the general population raises the importance of acquaintance with this disease in clinical practice.

A case report with the peculiar concomitance of 2 different genetic syndromes.

RATIONALE: Down syndrome (DS) is the most common chromosome disorder in live born infants, affecting several body systems, but usually sparing skeletal muscles. We present the case of a child with coexistence of DS and dystrophinopathy. Only 1 similar case has been reported so far. PATIENT CONCERNS: An 8-year-old boy with DS had a history of incidental finding of increased serum creatine kinase levels up to 1775 U/L (normal values 38-174 U/L). He presented no delay in motor development; at the neurological examination, no muscle weakness or fatigability was detected in 2 different evaluations performed over a 6-month period. DIAGNOSES: Skeletal muscle biopsy revealed marked dystrophic changes with patchy immunostaining for dystrophin. The Duchenne muscular dystrophy gene was screened for deletions by multiplex polymerase chain reaction, but no mutations were found. Sequence analysis of the Duchenne muscular dystrophy gene revealed a splice-site mutation c.1812+1G>A in intron 15 and confirmed a diagnosis of Becker muscular dystrophy. INTERVENTIONS: The patient has started a specific physiotherapy that avoided any deterioration in motor development and muscular wasting. OUTCOMES: A multidisciplinary follow-up was initiated. The genetician that followed the patient for DS was supported by the neurologist, the physiotherapist, the pulmonologist, and the cardiologist. LESSONS: This peculiar "double trouble" case exemplifies the value of careful clinical evaluation and adequate clinical experience to identify the concomitance of 2 different genetic syndromes in the same patient, and it points out the significance of muscular strength assessment in DS patients to make the most correct prognosis, and, consequently, to organize the best long-term care.

Charles Bonnet syndrome: two case reports and review of the literature.

Visual hallucinations (VHs) can be associated with a variety of clinical conditions, and are also experienced by healthy people due to visual impairment. The condition is known as Charles Bonnet Syndrome (CBS). The circumstances favoring VHs support the hypothesis that sensory deprivation enhances the ongoing activity of the visual system after sensory loss. Clinician should be aware that a significant proportion of visually impaired patients experience complex VHs, which are sometimes distressing. Herein, we report two cases of CBS. Case 1 is a 60-year-old man with visual impairment due to orbit pseudotumor in autoimmune hypothyroidism. Case 2 is an 87-year-old woman with Parkinson's disease and a 15-year history of intermittent complex VHs due to age-related macular degeneration in both eyes. In both cases investigations for alternative pathological causes of VHs were negative and, therefore, the aetiology of hallucinations was attributed to CBS. The course and treatment of CBS patients vary according to the nature of the visual dysfunction. Drug treatments remain partially satisfactory, with individual cases successfully treated with atypical antipsychotics. Nonpharmacological interventions aimed to reduce the visual pathway deprivation. Reassurance of the benign nature of CBS is essential to support patients and reduce caregiver's burden.

Quantitative muscle strength assessment in duchenne muscular dystrophy: longitudinal study and correlation with functional measures.

BACKGROUND: The aim of this study was to perform a longitudinal assessment using Quantitative Muscle Testing (QMT) in a cohort of ambulant boys affected by Duchenne muscular dystrophy (DMD) and to correlate the results of QMT with functional measures. This study is to date the most thorough long-term evaluation of QMT in a cohort of DMD patients correlated with other measures, such as the North Star Ambulatory Assessment (NSAA) or three 6-min walk test (6MWT). METHODS: This is a single centre, prospective, non-randomised, study assessing QMT using the Kin Com(®) 125 machine in a study cohort of 28 ambulant DMD boys, aged 5 to 12 years. This cohort was assessed longitudinally over a 12 months period of time with 3 monthly assessments for QMT and with assessment of functional abilities, using the NSAA and the 6MWT at baseline and at 12 months only. QMT was also used in a control group of 13 healthy age-matched boys examined at baseline and at 12 months. RESULTS: There was an increase in QMT over 12 months in boys below the age of 7.5 years while in boys above the age of 7.5 years, QMT showed a significant decrease. All the average one-year changes were significantly different than those experienced by healthy controls. We also found a good correlation between quantitative tests and the other measures that was more obvious in the stronger children. CONCLUSION: Our longitudinal data using QMT in a cohort of DMD patients suggest that this could be used as an additional tool to monitor changes, providing additional information on segmental strength.

Effects of rituximab in two patients with dysferlin-deficient muscular dystrophy.

BACKGROUND: The administration of rituximab (RTX) in vivo results in B-cell depletion, but evidence for multiple mechanisms of action have been reported. Surprisingly, B cell depletion produced a response in patients with polymyositis, which is characterized as a T cell-mediated autoimmune disorder with biopsy findings similar to Miyoshi myopathy (MM). Indeed, in dysferlinopathies, there is evidence of immune system involvement including the presence of muscle inflammation and a down regulation of the complement inhibitory factor, CD55. METHODS: Two patients were treated with four weekly infusions of RTX 375 mg/m2. To measure the improvement in muscle strength after treatment, the isometric hand grip maximal voluntary contraction (MVC) was measured by load cell four times during treatment, and again after one year. In order to assess the reproducibility of our grip assessment, we determined the hand MVC analysis in 16 healthy subjects. Moreover, we measured the number of B cells present in patients by flow cytometric analysis during the course of treatment. RESULTS: The analysis of B cell number during the course of treatment showed that CD20- and CD19-positive cells were depleted to 0-0.01%. The decrease in B cells was followed by an improvement in the mobility of the pelvic and shoulder girdles as shown by the MRC%. The MVC values of both patients began at values lower than normal whereas during treatment patients had improved percentage of muscle strength. The strength peak in both patients coincided with the minimum B cell values. There were no severe adverse events associated with an infusion of RTX. CONCLUSION: We consider the increase in muscle strength observed in both treated patients to be a consequence of their treatment with RTX. To our knowledge, these are the first cases of increased muscle strength in patients with MM. Furthermore, the results of this study indicate that B cell depletion with RTX may be useful in the treatment of patients affected by MM, suggesting a possible role for B cells in the pathophysiology of this muscle disorder.