When the diagnosis is in the patient's hand and in the neurologist's eye.

The objective of this study was to encompass current knowledge about pathophysiological mechanisms of those specific hand postures or deformities caused by central nervous system disorders. In the era of high-resolution neuroimaging and molecular biology, clinicians are progressively losing confidence with neurological examination. Careful hand observation is of key importance in order to differentiate neurological from non-neurological conditions, central from peripheral aetiologies, and organic from functional disorders. Localizing the potential anatomical site is essential to properly conduct subsequent exams. We provided a practical guide for clinicians to recognize hand patterns caused by central nervous system disorders, avoiding mimicking conditions, thus optimizing and prompting the diagnostic pathway.

Phenotypic spectrum of myelin protein zero-related neuropathies: a large cohort study from five mutation clusters across Italy.

BACKGROUND: We aimed to investigate the clinical features of a large cohort of patients with myelin protein zero (MPZ)-related neuropathy, focusing on the five main mutation clusters across Italy. METHODS: We retrospectively gathered a minimal data set of clinical information in a series of patients with these frequent mutations recruited among Italian Charcot-Marie-Tooth (CMT) registry centres, including disease onset/severity (CMTES-CMT Examination Score), motor/sensory symptoms and use of orthotics/aids. RESULTS: We collected data from 186 patients: 60 had the p.Ser78Leu variant ('classical' CMT1B; from Eastern Sicily), 42 the p.Pro70Ser (CMT2I; mainly from Lombardy), 38 the p.Thr124Met (CMT2J; from Veneto), 25 the p.Ser44Phe (CMT2I; from Sardinia) and 21 the p.Asp104ThrfsX13 (mild CMT1B; from Apulia) mutation. Disease severity (CMTES) was higher (p<0.001) in late-onset axonal forms (p.Thr124Met=9.2±6.6; p.Ser44Phe=7.8±5.7; p.Pro70Ser=7.6±4.8) compared with p.Ser78Leu (6.1±3.5) patients. Disease progression (ΔCMTES/year) was faster in the p.Pro70Ser cohort (0.8±1.0), followed by p.Ser44Phe (0.7±0.4), p.Thr124Met (0.4±0.5) and p.Ser78Leu (0.2±0.4) patients. Disease severity (CMTES=1.2±1.5), progression (ΔCMTES/year=0.1±0.4) and motor involvement were almost negligible in p.Asp104ThrfsX13 patients, who, however, frequently (78%, p<0.001) complained of neuropathic pain. In the other four clusters, walking difficulties were reported by 69-85% of patients, while orthotic and walking aids use ranged between 40-62% and 16-28%, respectively. CONCLUSIONS: This is the largest MPZ (and late-onset CMT2) cohort ever collected, reporting clinical features and disease progression of 186 patients from five different clusters across Italy. Our findings corroborate the importance of differentiating between 'classical' childhood-onset demyelinating, late-onset axonal and mild MPZ-related neuropathy, characterised by different pathomechanisms, in view of different therapeutic targets.

Role of Follicle-stimulating Hormone, Inhibin B, and Anti-Müllerian Hormone in Predicting Sperm Retrieval from Men with Nonobstructive Azoospermia Undergoing Microdissection Testicular Sperm Extraction: A Systematic Review and Meta-analysis.

Background and objective: No clear-cut markers for predicting positive sperm retrieval (+SR) at microdissection testicular sperm extraction (mTESE) have been identified thus far. Our aim was to conduct a systematic review and meta-analysis to evaluate the ability of follicle-stimulating hormone (FSH), inhibin B (InhB), and anti-Müllerian hormone (AMH) to predict +SR in men with nonobstructive azoospermia (NOA) undergoing mTESE. Methods: We performed a search in the PubMed, EMBASE, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Thirty-four publications were selected for inclusion in the analysis. Key findings and limitations: Overall, the mean +SR rate was 45%. Pooled standardized mean difference (SMD) values revealed significant hormonal differences between the +SR and -SR groups, with lower FSH (SMD -0.30), higher InhB (SMD 0.54), and lower AMH (SMD -0.56) levels in the +SR group. Pooled odds ratios (Ors) revealed no significant prediction of +SR by either FSH (OR 1.03, 95% confidence interval [CI] 1.00-1.06) or InhB (OR 1.01, 95% CI 1.00-1.02), despite variations in baseline levels and study heterogeneity. Conversely, AMH had significant predictive value (OR 0.82, 95% CI 0.73-0.92), with lower baseline levels in the +SR group. InhB and FSH levels were higher in the +SR group, while InhB exhibited the opposite trend. Conclusions and clinical implications: Despite study heterogeneity, our meta-analysis findings support the ability of AMH to predict +SR for men with NOA undergoing mTESE. Patient summary: We conducted a review and analysis of results from previous studies. Our findings show that for men with an infertility condition called nonobstructive azoospermia, blood levels of anti-Müllerian hormone can predict successful extraction of sperm using a microsurgical technique. Levels of two other hormones did not predict successful sperm extraction.

Spontaneous erectile function recovery among young men with erectile dysfunction taking tadalafil 5 mg once a day.

BACKGROUND: Daily (once a day [OaD]) tadalafil intake is a valuable option for men favoring spontaneous over scheduled sexual intercourse. AIM: The study sought to assess the rate of and the clinical factors associated with spontaneous, medication-free erectile function (EF) recovery after discontinuation of tadalafil 5 mg OaD in a cohort of young men seeking first medical help for psychogenic erectile dysfunction (ED) as their primary complaint. METHODS: Data from 96 consecutive patients <50 years of age seeking first medical help for ED and prescribed tadalafil 5 mg OaD were analyzed. Patients completed the International Index of Erectile Function (IIEF) and underwent baseline penile color Doppler ultrasound. Follow-up involved clinical assessments or phone interviews. Spontaneous medication-free EF recovery was defined as IIEF EF domain score >22 after tadalafil discontinuation, prompting cessation of follow-up. Descriptive statistics compared tadalafil OaD responders and nonresponders. Cox regression hazard models explored the association between baseline characteristics and EF recovery risk post-drug discontinuation. Kaplan-Meier analyses estimated EF recovery probability over time. OUTCOMES: The primary outcome was EF recovery after discontinuation of tadalafil 5 mg OaD. RESULTS: Overall, median age was 39 (interquartile range [IQR], 32-45) years. Of all, 82 (85.4%) patients achieved EF recovery after tadalafil OaD discontinuation, while 14 (14.6%) patients were identified as nonresponders. Median tadalafil usage time (from beginning to discontinuation) was 3 (IQR, 2-11) months. The most common treatment-emergent adverse event was headache in 9 (9.4%) patients. Nonresponders were older (43 [IQR, 42-45] years vs 38 [IQR, 31-44] years; P = .03), had higher body mass index (25.5 [IQR, 23.4-29.9] kg/m2 vs 23.6 [IQR, 21.8-25.9] kg/m2; P = .04), and reported lower baseline IIEF EF domain scores (12 [IQR, 7-15] vs 15 [IQR, 10-22]; P = .02) than responders. Nonresponders and responders did not differ in terms of baseline ED severity, Charlson comorbidity index, smoking, alcohol consumption, regular physical exercise, and color Doppler ultrasound parameters. Upon Cox regression analysis, younger age (hazard ratio, 0.95; 95% confidence interval, 0.92-0.99; P = .01) was associated to EF recovery, after adjusting for baseline ED severity, body mass index, smoking, and Charlson comorbidity index ≥1. The Kaplan-Meier analysis displays the probability of EF recovery over time, indicating rates of 43%, 60%, and 72% at 3-, 6-, and 12-month follow-up intervals, respectively. CLINICAL IMPLICATIONS: Tadalafil 5 mg OaD is an effective short-term treatment for psychogenic ED, allowing its discontinuation after achieving a normal medication-free EF. STRENGTHS AND LIMITATIONS: The main limitations are the limited number of participants and the potential neglect of confounding factors. CONCLUSION: Almost 1 out of 2 young men with primary psychogenic ED who were prescribed with tadalafil 5 mg OaD recovered spontaneous medication-free EF after 3 months of treatment. Overall, the younger the patient was, the higher the chance there was of spontaneous EF recovery after drug discontinuation.

Unrecognised orgasmic phase disorders in men presenting with new-onset erectile dysfunction-Findings from a real-life, cross-sectional study.

BACKGROUND: Orgasmic phase disorders in men worsen the burden of erectile dysfunction on sexual satisfaction. OBJECTIVES: To investigate the prevalence of and predictors of unreported orgasmic phase disorder in a cohort of men looking for their first urological assessment for new-onset erectile dysfunction in a real-life setting. MATERIALS AND METHODS: Data from 1107 heterosexual, sexually active men consecutively assessed for new-onset erectile dysfunction were analysed. Throughout a comprehensive medical and sexual history, all patients were asked to self-report any orgasmic phase disorder and to complete the International Index of Erectile Function and the Beck's Inventory for Depression (depressive symptoms scored as Beck's Inventory for Depression ≥11). Men self-reporting orgasmic phase disorder during the interview were excluded from further analyses. The median value of the International Index of Erectile Function-orgasmic function domain was arbitrarily used to categorise men with (International Index of Erectile Function-orgasmic function ≤5) and without unreported orgasmic phase disorder (International Index of Erectile Function-orgasmic function >5). Circulating hormones were measured in every patient. Descriptive statistics and logistic regression models were used to test the association between clinical variables and unreported orgasmic phase disorder. RESULTS: Of 1098 patients with non-self-reporting orgasmic phase disorder, 314 (28.6%) had International Index of Erectile Function-orgasmic function ≤5. Patients with erectile dysfunction + unreported orgasmic phase disorder were older (median [interquartile range]: 58 [44-66] years vs. 51 [40-60] years), had higher body mass index [25.8 (23.7-28.1) kg/m2 vs. 25.2 (23.3-27.4) kg/m2 ], higher prevalence of type 2 diabetes (36 [11.5%] vs. 45 [5.7%]) and lower International Index of Erectile Function-erectile function scores (6 [2-10] vs. 18 [11-24]) than men with erectile dysfunction-only (all p < 0.05). Patients with erectile dysfunction + unreported orgasmic phase disorder depicted higher rates of severe erectile dysfunction (75.5% vs. 25%) and Beck's Inventory for Depression ≥11 (22.6% vs. 17.9%) (all p < 0.05). In the multivariable logistic regression analysis, older age (odds ratio: 1.02) and lower International Index of Erectile Function-erectile function scores (odds ratio: 0.83) were independently associated with unreported orgasmic phase disorder (all p < 0.05). CONCLUSIONS: Almost one in three men seeking first medical help for erectile dysfunction depicted criteria suggestive of unreported orgasmic phase disorder. Men with unreported orgasmic phase disorder were older and had higher rates of severe erectile dysfunction and concomitant depressive symptoms. These real-life findings outline the clinical relevance of a comprehensive investigation of concomitant sexual dysfunction in men only complaining of erectile dysfunction to more effectively tailor patient management.

Use, tolerability, benefits and side effects of orthotic devices in Charcot-Marie-Tooth disease.

BACKGROUND: Shoe inserts, orthopaedic shoes, ankle-foot orthoses (AFOs) are important devices in Charcot-Marie-Tooth disease (CMT) management, but data about use, benefits and tolerance are scanty. METHODS: We administered to Italian CMT Registry patients an online ad hoc questionnaire investigating use, complications and perceived benefit/tolerability/emotional distress of shoe inserts, orthopaedic shoes, AFOs and other orthoses/aids. Patients were also asked to fill in the Quebec User Evaluation of Satisfaction with assistive Technology questionnaire, rating satisfaction with currently used AFO and related services. RESULTS: We analysed answers from 266 CMT patients. Seventy per cent of subjects were prescribed lower limb orthoses, but 19% did not used them. Overall, 39% of subjects wore shoe inserts, 18% orthopaedic shoes and 23% AFOs. Frequency of abandonment was high: 24% for shoe inserts, 28% for orthopaedic shoes and 31% for AFOs. Complications were reported by 59% of patients and were more frequently related to AFOs (69%). AFO users experienced greater emotional distress and reduced tolerability as compared with shoe inserts (p<0.001) and orthopaedic shoes (p=0.003 and p=0.045, respectively). Disease severity, degree of foot weakness, customisation and timing for customisation were determinant factors in AFOs' tolerability. Quality of professional and follow-up services were perceived issues. CONCLUSIONS: The majority of CMT patients is prescribed shoe inserts, orthopaedic shoes and/or AFOs. Although perceived benefits and tolerability are rather good, there is a high rate of complications, potentially inappropriate prescriptions and considerable emotional distress, which reduce the use of AFOs. A rational, patient-oriented and multidisciplinary approach to orthoses prescription must be encouraged.

Carotid free-floating thrombus stemming from carotid web: co-occurrence of two rare causes of ischemic stroke.

BACKGROUND: Carotid web (CaW) and carotid free-floating thrombus (CFFT) are rare yet critical causes of ischemic stroke in young adults. CASE PRESENTATION: A 54-year-old woman presented with a fluctuating right sensory-motor faciobrachial syndrome. A brain MRI scan revealed multiple small recent asynchronous cortico-subcortical ischemic foci in the vascular territory of the left internal carotid artery. A CT angiography identified a CFFT in the left internal carotid artery arising from an underlying CaW. The patient was treated with excellent clinical outcomes with carotid artery stenting and dual antiplatelet therapy. CONCLUSIONS: We provide a structured pathophysiological rationale connecting CaW and CFFT and highlight pivotal therapeutic implications. Further studies are needed to investigate this relationship and guide assessment and treatment.

Is SARS-CoV-2-induced disease a decisive factor influencing testosterone in males? Findings from a case-control ex post facto study.

BACKGROUND: Whether the observed lower total testosterone (tT) levels in male patients with COVID-19 are caused by a direct impact of SARS-CoV-2 infection or are collateral phenomena shared by other systemic inflammatory conditions has not yet been clarified. OBJECTIVES: To investigate the independent role of COVID-19 in reducing circulating tT levels in men. MATERIALS AND METHODS: We compared demographic, clinical, and hormonal values of patients with laboratory confirmed COVID-19 admitted during the first wave of the pandemic with a cohort of consecutive male patients admitted to the intensive care unit (ICU) of the same academic center because of severe acute respiratory distress syndrome (ARDS) but without SARS-CoV-2 infection and no previous history of COVID-19. Linear regression model tested the independent impact of COVID-19 on circulating tT levels. Logistic regression model was used to test predictors of death in the entire cohort. RESULTS: Of 286 patients with COVID-19, 70 men had been admitted to the ICU ( = cases) and were compared to 79 patients equally admitted to ICU because of severe ARDS but negative for SARS-CoV-2 infection and without previous history of COVID-19 ( = controls). Controls were further grouped into noninfective (n = 49) and infective-ARDS (n = 30) patients. At baseline, controls were older (p = 0.01) and had more comorbidities (p < 0.0001). Overall, cases admitted to ICU had significantly lower circulating tT levels compared to controls (0.9 nmol/L vs. 2.1 nmol/L; vs. 1.2 nmol/L; p = 0.03). At linear regression, being negative for COVID-19 was associated with higher tT levels (Coeff: 2.13; 95% confidence interval - CI 0.71-3.56; p = 0.004) after adjusting for age, BMI, comorbidities and IL-6 levels. Only age and IL-6 levels emerged to be associated with higher risk of death regardless of COVID-19 status. CONCLUSIONS: This case-control ex post facto study showed lower tT levels in men with COVID-19 compared to those without COVID-19 despite both groups have been equally admitted to ICU for severe ARDS, thus suggesting a possible direct impact of SARS-CoV-2 infection toward circulating tT levels and a consequent more severe clinical outcome.

Daytime sleepiness and sleep quality in Charcot-Marie-Tooth disease.

BACKGROUND: Sleep abnormalities have been reported in Charcot-Marie-Tooth disease (CMT), but data are scanty. We investigated their presence and correlation in a large CMT patients' series. METHODS: Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were administered to CMT patients of the Italian registry and controls. ESS score > 10 indicated abnormal daytime somnolence, PSQI score > 5 bad sleep quality. We analyzed correlation with disease severity and characteristics, Hospital Anxiety and Depression Scale (HADS), Modified Fatigue Impact Scale (MFIS), Body Mass Index, drug use. RESULTS: ESS and PSQI questionnaires were filled by 257 and 253 CMT patients, respectively, and 58 controls. Median PSQI score was higher in CMT patients than controls (6 vs 4, p = 0.006), with no difference for ESS score. Abnormal somnolence and poor sleep quality occurred in 23% and 56% of patients; such patients had more frequently anxiety/depression, abnormal fatigue, and positive sensory symptoms than those with normal ESS/PSQI. Moreover, patients with PSQI score > 5 had more severe disease (median CMT Examination Score, CMTES, 8 vs 6, p = 0.006) and more frequent use of anxiolytic/antidepressant drugs (29% vs 7%, p < 0.001). CONCLUSIONS: Bad sleep quality and daytime sleepiness are frequent in CMT and correlated with anxiety, depression and fatigue, confirming that different components affect sleep. Sleep disorders, such as sleep apnea and restless leg syndrome, not specifically investigated here, are other factors known to impact on sleep quality and somnolence. CMT patients' management must include sleep behavior assessment and evaluation of its correlated factors, including general distress and fatigue.

A review on pharmacological options for the treatment of erectile dysfunction: state of the art and new strategies.

INTRODUCTION: Erectile dysfunction (ED) affects between 12.9% and 28.1% of men worldwide, presenting a strong aged-correlated prevalence. Several pharmacological treatments are currently available for ED, which can be classified into oral, injection, and topical/intraurethral therapies. AREAS COVERED: Extensive research on PubMed/MEDLINE until February 2023 was performed. For each of the aforementioned drug classes, available molecules, and formulations, their efficacy and most common adverse events as well as general guidelines on prescription were investigated and extensively described. A glimpse into future directions regarding ED pharmacotherapy is also present. EXPERT OPINION: In recent years, there have been significant developments in pharmacological treatments for ED. It is essential for physicians to identify the best treatment option for patients based on their preferences and sexual habits. The treatment approach for ED has shifted from a sequential to a parallel paradigm, where all treatment options are available as first-line therapies. While there are promising regenerative therapies for ED, such as shockwaves and platelet-rich plasma injections, pharmacological treatment is still the most effective option for most patients.

Clinical spectrum and frequency of Charcot-Marie-Tooth disease in Italy: Data from the National CMT Registry.

BACKGROUND AND PURPOSE: Data are reported from the Italian CMT Registry. METHODS: The Italian CMT Registry is a dual registry where the patient registers and chooses a reference center where the attending clinician collects a minimal dataset of information and administers the Charcot-Marie-Tooth (CMT) Examination/Neuropathy Score. Entered data are encrypted. RESULTS: Overall, 1012 patients had registered (535 females) and 711 had received a genetic diagnosis. Demyelinating CMT (65.3%) was more common than axonal CMT2 (24.6%) and intermediate CMT (9.0%). The PMP22 duplication was the most frequent mutation (45.2%), followed by variants in GJB1 and MPZ (both ~10%) and MFN2 (3.3%) genes. A relatively high mutation rate in some "rare" genes (HSPB1 1.6%, NEFL 1.5%, SH3TC2 1.5%) and the presence of multiple mutation clusters across Italy was observed. CMT4A was the most disabling type, followed by CMT4C and CMT1E. Disease progression rate differed depending on the CMT subtype. Foot deformities and walking difficulties were the main features. Shoe inserts and orthotic aids were used by almost one-half of all patients. Scoliosis was present in 20% of patients, especially in CMT4C. Recessive forms had more frequently walking delay, walking support need and wheelchair use. Hip dysplasia occurred in early-onset CMT. CONCLUSIONS: The Italian CMT Registry has proven to be a powerful data source to collect information about epidemiology and genetic distribution, clinical features and disease progression of CMT in Italy and is a useful tool for recruiting patients in forthcoming clinical trials.

The atherosclerotic cardiovascular disease risk score is a reliable tool to identify patients with arteriogenic erectile dysfunction.

BACKGROUND: The atherosclerotic cardiovascular disease risk score is a validated algorithm predicting an individual's 10-year risk of developing acute cardiovascular events (cardiovascular disease). Patients who suffer from arteriogenic erectile dysfunction are susceptible to developing cardiovascular disease in the future. OBJECTIVES: To apply the atherosclerotic cardiovascular disease score at a homogenous cohort of men with erectile dysfunction undergoing a dynamic penile colour Doppler duplex ultrasound and explore its predictive ability to identify patients with vasculogenic erectile dysfunction at colour Doppler duplex ultrasound. MATERIALS AND METHODS: Complete data of 219 patients undergoing colour Doppler duplex ultrasound were analysed. All patients completed the International Index of Erectile Function. The atherosclerotic cardiovascular disease score and Charlson comorbidity index were applied to the entire cohort. Patients were divided into those with normal vs. pathological parameters at colour Doppler duplex ultrasound. Descriptive statistics were used to explore differences between the two groups. Logistic regression models tested the potential role of atherosclerotic cardiovascular disease to predict arteriogenic and/or venogenic erectile dysfunction. Local polynomial smoothing models graphically displayed the probability of pathological colour Doppler duplex ultrasound parameters at different atherosclerotic cardiovascular disease scores. RESULTS: Overall, arteriogenic erectile dysfunction and venous leakage were diagnosed in 88 (40.2%) and 28 (12.8%) patients respectively. The median (interquartile range) atherosclerotic cardiovascular disease score was 7.7 (3.9-14). Patients with pathologic colour Doppler duplex ultrasound were older (59 vs. 54 years, p < 0.001), had higher Body Mass Index (26.5 vs. 25.6 kg/m2 , p = 0.04), more comorbidities (Charlson comorbidity index ≥ 1) (76.5% vs. 54.4%, p = 0.002) and higher median atherosclerotic cardiovascular disease scores (9.95 vs. 7, p = 0.005), respectively. At logistic regression analysis, a higher atherosclerotic cardiovascular disease risk score was independently associated with arteriogenic erectile dysfunction at colour Doppler duplex ultrasound (odds ratio: 1.03, 95% confidence interval: 1.01-1.08, p = 0.02) after adjusting for Body Mass Index, physical activity, alcohol consumption and severe erectile dysfunction. DISCUSSION: As vasculogenic erectile dysfunction may precede by some years the onset of acute cardiovascular diseases, the rigorous identification of patients with deficient cavernosal arterial blood flow, would definitely allow the implementation of earlier and more effective cardiovascular prevention strategies in men with erectile dysfunction. CONCLUSIONS: The atherosclerotic cardiovascular disease risk score represents a reliable tool to identify patients with arteriogenic erectile dysfunction in everyday clinical practice.

Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series.

INTRODUCTION: Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG). MATERIALS AND METHODS: Twelve patients were enrolled (mean age, 47.7 ± 11.6 years), referred to our attention because of myalgia, pain, or muscle cramps, which persisted about 6 months after the diagnosis of SARS-CoV-2 infection. They underwent conventional electroneurography (ENG), needle electromyography (EMG), and SSRs; moreover, qEMG was performed by sampling at least 20 motor unit potentials (20-30 MUPs) during weak voluntary contraction in deltoid and tibialis anterior muscles. The mean duration, amplitude, and percentage of polyphasic potentials were assessed and compared with healthy and age-matched volunteers. RESULTS: ENG did not disclose significant changes compared to healthy subjects; needle EMG did not reveal denervation activity. In addition, qEMG showed MUPs similar to those recorded in healthy volunteers in terms of polyphasia (deltoid: p = 0.24; TA: p = 0.35), MUP area (deltoid: p = 0.45; TA: p = 0.44), mean duration (deltoid: p = 0.06; TA: p = 0.45), and amplitude (deltoid: p = 0.27; TA: p = 0.63). SSRs were not recordable from lower limbs in seven patients (58%) and from the upper ones in three of them (25%). CONCLUSION: Our data suggest an involvement of the autonomic system, with a focus on cholinergic efferent sympathetic activity, without any evidence of myopathic changes.

Anxiety and depression in Charcot-Marie-Tooth disease: data from the Italian CMT national registry.

BACKGROUND: There is little information about neuropsychiatric comorbidities in Charcot-Marie-Tooth disease (CMT). We assessed frequency of anxiety, depression, and general distress in CMT. METHODS: We administered online the Hospital Anxiety-Depression Scale (HADS) to CMT patients of the Italian registry and controls. HADS-A and HADS-D scores ≥ 11 defined the presence of anxiety/depression and HADS total score (HADS-T) ≥ 22 of general distress. We analysed correlation with disease severity and clinical characteristics, use of anxiolytics/antidepressants and analgesic/anti-inflammatory drugs. RESULTS: We collected data from 252 CMT patients (137 females) and 56 controls. CMT patient scores for anxiety (mean ± standard deviation, 6.7 ± 4.8), depression (4.5 ± 4.0), and general distress (11.5 ± 8.1) did not differ from controls and the Italian population. However, compared to controls, the percentages of subjects with depression (10% vs 2%) and general distress (14% vs 4%) were significantly higher in CMT patients. We found no association between HADS scores and disease duration or CMT type. Patients with general distress showed more severe disease and higher rate of positive sensory symptoms. Depressed patients also had more severe disease. Nineteen percent of CMT patients took antidepressants/anxiolytics (12% daily) and 70% analgesic/anti-inflammatory drugs. Patients with anxiety, depression, and distress reported higher consumption of anxiolytics/antidepressants. About 50% of patients with depression and/or general distress did not receive any specific pharmacological treatment. CONCLUSIONS: An appreciable proportion of CMT patients shows general distress and depression. Both correlated with disease severity and consumption of antidepressants/anxiolytics, suggesting that the disease itself is contributing to general distress and depression.

Frequency, entity and determinants of fatigue in Charcot-Marie-Tooth disease.

BACKGROUND AND PURPOSE: Fatigue, a disabling symptom in many neuromuscular disorders, has been reported also in Charcot-Marie-Tooth disease (CMT). The presence of fatigue and its correlations in CMT was investigated. METHODS: The Modified Fatigue Impact Scale (MFIS) was administered to CMT patients from the Italian Registry and a control group. An MFIS score >38 indicated abnormal fatigue. The correlation with disease severity and clinical characteristics, the Hospital Anxiety and Depression Scale and Epworth Sleepiness Scale scores, and drug use was analysed. RESULTS: Data were collected from 251 CMT patients (136 women) and 57 controls. MFIS total (mean ± standard deviation 32 ± 18.3, median 33), physical (18.9 ± 9.7, 20) and psychosocial (2.9 ± 2.4, 3) scores in CMT patients were significantly higher than controls. Abnormal fatigue occurred in 36% of the patients who, compared to patients with normal scores, had more severe disease (median CMT Examination Score 9 vs. 7), more frequent use of foot orthotics (22% vs. 11%), need of support for walking (21% vs. 8%), hand disability (70% vs. 52%) and positive sensory symptoms (56% vs. 36%). Patients with abnormal fatigue had significantly increased frequency of anxiety/depression/general distress (Hospital Anxiety and Depression Scale), somnolence (Epworth Sleepiness Scale), obesity (body mass index ≥ 30) and use of anxiolytic/antidepressant or anti-inflammatory/analgesic drugs. CONCLUSIONS: Fatigue is a relevant symptom in CMT as 36% of our series had scores indicating abnormal fatigue. It correlated with disease severity but also with anxiety, depression, sleepiness and obesity, indicating different components in the generation of fatigue. CMT patients' management must include treatment of fatigue and of its different generators, including general distress, sleepiness and obesity.

Neuroprotection and Non-Invasive Brain Stimulation: Facts or Fiction?

Non-Invasive Brain Stimulation (NIBS) techniques, such as transcranial Direct Current Stimulation (tDCS) and repetitive Magnetic Transcranial Stimulation (rTMS), are well-known non-pharmacological approaches to improve both motor and non-motor symptoms in patients with neurodegenerative disorders. Their use is of particular interest especially for the treatment of cognitive impairment in Alzheimer's Disease (AD), as well as axial disturbances in Parkinson's (PD), where conventional pharmacological therapies show very mild and short-lasting effects. However, their ability to interfere with disease progression over time is not well understood; recent evidence suggests that NIBS may have a neuroprotective effect, thus slowing disease progression and modulating the aggregation state of pathological proteins. In this narrative review, we gather current knowledge about neuroprotection and NIBS in neurodegenerative diseases (i.e., PD and AD), just mentioning the few results related to stroke. As further matter of debate, we discuss similarities and differences with Deep Brain Stimulation (DBS)-induced neuroprotective effects, and highlight possible future directions for ongoing clinical studies.

Single-cell transcriptome profiling reveals several LncRNAs differentially expressed in idiopathic germ cell aplasia.

Mechanisms underlying severe male infertility are still largely elusive. However, recently, a single-cell transcription study by our group identified several differentially expressed coding genes in all the somatic cell types in testes of patients with idiopathic germ cell aplasia (iGCA). Here, we leverage this work by extending the analysis also to the non-coding portion of the genome. As a result, we found that 43 LncRNAs were differentially expressed in the somatic cells of these patients. Interestingly, a significant portion of the overexpressed LncRNAs was found to be a target of TAF9B, a transcription factor known to be involved in germ cell survival. Moreover, several overexpressed LncRNAs were also found to be activated in a mouse model of Sertoli cells treated with bisphenol A, a widespread environmental contaminant, long suspected to impair male fertility. Finally, a literature search for MEG3, a maternally imprinted LncRNA overexpressed as well in our patients, found it to be involved, among other things, in obesity and inflammation, known comorbidities of iGCA, ultimately suggesting that our findings deepen the understanding of the molecular insights coupled not only to the pathogenesis, but also to the clinical course of this class of patients.

Movement disorders and neuropathies: overlaps and mimics in clinical practice.

Movement disorders as well as peripheral neuropathies are extremely frequent in the general population; therefore, it is not uncommon to encounter patients with both these conditions. Often, the coexistence is coincidental, due to the high incidence of common causes of peripheral neuropathy, such as diabetes and other age-related disorders, as well as of Parkinson disease (PD), which has a typical late onset. Nonetheless, there is broad evidence that PD patients may commonly develop a sensory and/or autonomic polyneuropathy, triggered by intrinsic and/or extrinsic mechanisms. Similarly, some peripheral neuropathies may develop some movement disorders in the long run, such as tremor, and rarely dystonia and myoclonus, suggesting that central mechanisms may ensue in the pathogenesis of these diseases. Although rare, several acquired or hereditary causes may be responsible for the combination of movement and peripheral nerve disorders as a unique entity, some of which are potentially treatable, including paraneoplastic, autoimmune and nutritional aetiologies. Finally, genetic causes should be pursued in case of positive family history, young onset or multisystemic involvement, and examined for neuroacanthocytosis, spinocerebellar ataxias, mitochondrial disorders and less common causes of adult-onset cerebellar ataxias and spastic paraparesis. Deep phenotyping in terms of neurological and general examination, as well as laboratory tests, neuroimaging, neurophysiology, and next-generation genetic analysis, may guide the clinician toward the correct diagnosis and management.

The role of inelastic deformations in the mechanical response of endovascular shape memory alloy devices.

Nickel-titanium alloys are commonly adopted for producing cardiovascular minimally invasive devices such as self-expandable stents, aortic valves and stent-grafts. These devices are subjected to cyclic loads (due to blood pulsatility, leg or heart movements), that can induce fatigue fracture, and may also be subjected to very large deformations (due to crimping procedure, a tortuous physiological path or overloads), that can induce material yield. Recently, the authors developed a new constitutive model that considers inelastic strains due to not-completed reverse phase transformation (not all the stress-induced martensite turns back to austenite) or/and plasticity and their accumulation during cyclic loads. In this article, the model is implemented in the finite element code ABAQUS/Standard and it is used to investigate the effects of inelastic strain accumulation on endovascular nickel-titanium devices. In particular, the behavior of a transcatheter aortic valve is studied considering the following steps: (1) crimping, (2) expansion in a tube resembling a durability test chamber and (3) cyclic loads due to pressure variation applied on the inner surface of the tube. The analyses are performed twice, activating and not activating that part of the new model which describes the development of irreversible strain. From the results, it is interesting to note that plasticity has a very significant effect on the local material response, inducing stress modification from compression to tension. However, permanent deformations are concentrated in few zones of the stent frame and their presence does not affect the global behavior of the device that maintains its capability of recovering the original shape. In conclusion, this work suggests that at least for cardiovascular devices where the crimping is high (local strain may reach values of 8%-9%), taking into account inelastic effects due to plasticity and not-completed reverse phase transformation can be important, and hence using a suitable constitutive model is recommended.