Sexual dysfunction in multiple sclerosis: The impact of different MSISQ-19 cut-offs on prevalence and associated risk factors.

BACKGROUND: Although multiple sclerosis (MS) Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a widely applied tool, no unique definition of sexual dysfunction (SD) based on its score exists. OBJECTIVE: To explore the impact of different MSISQ-19 cut-offs on SD prevalence and associated risk factors, providing relevant information for its application in research and clinical settings. METHODS: After defining SD according to two different MSISQ-19 cut-offs in 1155 people with MS (pwMS), we evaluated SD prevalence and association with sociodemographic and clinical features, mood status and disability via logistic regression. RESULTS: Depending on the chosen cut-off, 45% to 54% of pwMS reported SD. SD defined as MSISQ-19 score >30 was predicted by age (OR=1.01, p=0.047), cognition (OR=0.96, p=0.004) and anxiety (OR=1.03, p=0.019). SD defined as a score >3 on any MSISQ-19 item was predicted by motor disability (OR=1.12, p=0.003) and cognition (OR= 0.96, p=0.002). CONCLUSION: Applying different MSISQ-19 cut-offs influences both the estimated prevalence and the identification of risk factors for SD, a finding that should be considered during study planning and data interpretation. Preserved cognition exerts a protective effect towards SD regardless from the specific study setting, representing a key point for the implementation of preventive and therapeutic strategies.

MR Imaging Signs of Gadolinium Retention Are Not Associated with Long-Term Motor and Cognitive Outcomes in Multiple Sclerosis.

BACKGROUND AND PURPOSE: The long-term impact of gadolinium retention in the dentate nuclei of patients undergoing administration of seriate gadolinium-based contrast agents is still widely unexplored. The aim of this study was to evaluate the impact of gadolinium retention on motor and cognitive disability in patients with MS during long-term follow-up. MATERIALS AND METHODS: In this retrospective study, clinical data were obtained from patients with MS followed in a single center from 2013 to 2022 at different time points. These included the Expanded Disability Status Scale score to evaluate motor impairment and the Brief International Cognitive Assessment for MS battery to investigate cognitive performances and their respective changes with time. The association with qualitative and quantitative MR imaging signs of gadolinium retention (namely, the presence of dentate nuclei T1-weighted hyperintensity and changes in longitudinal relaxation R1 maps, respectively) was probed using different General Linear Models and regression analyses. RESULTS: No significant differences in motor or cognitive symptoms emerged between patients showing dentate nuclei hyperintensity and those without visible changes on T1WIs (P = .14 and 0.92, respectively). When we tested possible relationships between quantitative dentate nuclei R1 values and both motor and cognitive symptoms, separately, the regression models including demographic, clinical, and MR imaging features explained 40.5% and 16.5% of the variance, respectively, without any significant effect of dentate nuclei R1 values (P = .21 and 0.30, respectively). CONCLUSIONS: Our findings suggest that gadolinium retention in the brains of patients with MS is not associated with long-term motor or cognitive outcomes.

The Minor's test in Frey syndrome treated with botulinum toxin: Methodology and efficacy.

In this paper, we aimed at methodologically presenting a video-case of Frey Syndrome occurred after parotidectomy, assessed by means of Minor's Test and treated with intradermic botulinum toxin A (BoNT-A) injection. Although largely described in the literature, a detailed explanation of both the procedures has not been previously elucidated. In a more original approach, we also highlighted the role of the Minor's test in identifying the most affected skin areas and new insight on the patient-tailored approach provided by multiple injections of botulinum toxin. Six months after the procedure, the patient's symptoms were resolved, and no evident signs of Frey syndrome were detectable through the Minor's test.

Quantitative MRI in Multiple Sclerosis: From Theory to Application.

Quantitative MR imaging techniques allow evaluating different aspects of brain microstructure, providing meaningful information about the pathophysiology of damage in CNS disorders. In the study of patients with MS, quantitative MR imaging techniques represent an invaluable tool for studying changes in myelin and iron content occurring in the context of inflammatory and neurodegenerative processes. In the first section of this review, we summarize the physics behind quantitative MR imaging, here defined as relaxometry and quantitative susceptibility mapping, and describe the neurobiological correlates of quantitative MR imaging findings. In the second section, we focus on quantitative MR imaging application in MS, reporting the main findings in both the gray and white matter compartments, separately addressing macroscopically damaged and normal-appearing parenchyma.

A Combined Radiomics and Machine Learning Approach to Overcome the Clinicoradiologic Paradox in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Conventional MR imaging explains only a fraction of the clinical outcome variance in multiple sclerosis. We aimed to evaluate machine learning models for disability prediction on the basis of radiomic, volumetric, and connectivity features derived from routine brain MR images. MATERIALS AND METHODS: In this retrospective cross-sectional study, 3T brain MR imaging studies of patients with multiple sclerosis, including 3D T1-weighted and T2-weighted FLAIR sequences, were selected from 2 institutions. T1-weighted images were processed to obtain volume, connectivity score (inferred from the T2 lesion location), and texture features for an atlas-based set of GM regions. The site 1 cohort was randomly split into training (n = 400) and test (n = 100) sets, while the site 2 cohort (n = 104) constituted the external test set. After feature selection of clinicodemographic and MR imaging-derived variables, different machine learning algorithms predicting disability as measured with the Expanded Disability Status Scale were trained and cross-validated on the training cohort and evaluated on the test sets. The effect of different algorithms on model performance was tested using the 1-way repeated-measures ANOVA. RESULTS: The selection procedure identified the 9 most informative variables, including age and secondary-progressive course and a subset of radiomic features extracted from the prefrontal cortex, subcortical GM, and cerebellum. The machine learning models predicted disability with high accuracy (r approaching 0.80) and excellent intra- and intersite generalizability (r ≥ 0.73). The machine learning algorithm had no relevant effect on the performance. CONCLUSIONS: The multidimensional analysis of brain MR images, including radiomic features and clinicodemographic data, is highly informative of the clinical status of patients with multiple sclerosis, representing a promising approach to bridge the gap between conventional imaging and disability.

Unraveling Deep Gray Matter Atrophy and Iron and Myelin Changes in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Modifications of magnetic susceptibility have been consistently demonstrated in the subcortical gray matter of MS patients, but some uncertainties remain concerning the underlying neurobiological processes and their clinical relevance. We applied quantitative susceptibility mapping and longitudinal relaxation rate relaxometry to clarify the relative contribution of atrophy and iron and myelin changes to deep gray matter damage and disability in MS. MATERIALS AND METHODS: Quantitative susceptibility mapping and longitudinal relaxation rate maps were computed for 91 patients and 55 healthy controls from MR images acquired at 3T. Applying an external model, we estimated iron and myelin concentration maps for all subjects. Subsequently, changes of deep gray matter iron and myelin concentration (atrophy-dependent) and content (atrophy-independent) were investigated globally (bulk analysis) and regionally (voxel-based and atlas-based thalamic subnuclei analyses). The clinical impact of the observed MRI modifications was evaluated via regression models. RESULTS: We identified reduced thalamic (P < .001) and increased pallidal (P < .001) mean iron concentrations in patients with MS versus controls. Global myelin and iron content in the basal ganglia did not differ between the two groups, while actual iron depletion was present in the thalamus (P < .001). Regionally, patients showed increased iron concentration in the basal ganglia (P ≤ .001) and reduced iron and myelin content in thalamic posterior-medial regions (P ≤ .004), particularly in the pulvinar (P ≤ .001). Disability was predicted by thalamic volume (B = -0.341, P = .02), iron concentration (B = -0.379, P = .005) and content (B = -0.406, P = .009), as well as pulvinar iron (B = -0.415, P = .003) and myelin (B = -0.415, P = .02) content, independent of atrophy. CONCLUSIONS: Quantitative MRI suggests an atrophy-related iron increase within the basal ganglia of patients with MS, along with an atrophy-independent reduction of thalamic iron and myelin correlating with disability. Absolute depletions of thalamic iron and myelin may represent sensitive markers of subcortical GM damage, which add to the clinical impact of thalamic atrophy in MS.

Streamline density and lesion volume reveal a postero-anterior gradient of corpus callosum damage in multiple sclerosis.

BACKGROUND AND PURPOSE: Although interhemispheric disconnection significantly contributes to disability in multiple sclerosis (MS), the topography, timeline and relationship of callosal damage accrual with hemispheric damage are still unclear. METHODS: Streamline density and the presence of focal lesions in five callosal subregions were computed in 55 people with MS [13 relapsing-remitting (RRMS), 20 secondary progressive (SPMS), 22 primary progressive (PPMS)] and 24 healthy controls. RESULTS: Streamline density decrease was identified in SPMS in all corpus callosum (CC) subregions, in PPMS in the posterior CC and mid-posterior CC and in RRMS in the posterior CC. CC density was independently predicted by CC lesion volume and hemispheric lesion volume and independently predicted visuospatial memory, Expanded Disability Status Scale, manual dexterity and ambulation. CONCLUSIONS: The reduction in CC density across phenotypes suggests an earlier involvement of the posterior regions, followed only at a later stage by involvement of the anterior portions of the CC. Such interhemispheric disconnection seems to develop as a consequence of white matter macroscopic damage and exerts a relevant impact on motor and, to a lesser extent, cognitive disability.

Axonal water fraction as marker of white matter injury in primary-progressive multiple sclerosis: a longitudinal study.

BACKGROUND AND PURPOSE: Diffuse white matter (WM) injury is prominent in primary-progressive multiple sclerosis (PP-MS) pathology and is a potential biomarker of disease progression. Diffusion kurtosis imaging allows the quantification of non-Gaussian water diffusion, providing metrics with high WM pathological specificity. The aim of this study was to characterize the pathological changes occurring in the normal-appearing WM of patients with PP-MS at baseline and at 1-year follow-up and to assess their impact on disability and short-term disease progression. METHODS: A total of 26 patients with PP-MS and 20 healthy controls were prospectively enrolled. Diffusion kurtosis imaging single-shot echo-planar imaging (EPI) was acquired on a 3-T scanner (Philips Achieva, Best, The Netherlands) (voxel size, 2 × 2 × 2 mm3 , 30 directions for each b-value = 1000, 2000 s/mm2 and one b = 0 s/mm2 ). A two-compartment biophysical model of WM tract integrity was used to derive spatial maps of axonal water fraction (AWF), intra-axonal diffusivity, extra-axonal axial and radial diffusivities (De,axial , De,radial ) and tortuosity from the following WM tracts: corpus callosum (CC), corticospinal tract (CST) and posterior thalamic radiation (PTR). RESULTS: At baseline, patients with PP-MS showed a widespread decrease of AWF, tortuosity and De,axial and an increase of De,radial in CC, CST and PTR (P ranging from 0.001 to 0.036). At 1-year follow-up, a significant AWF decrease was detected in the body of CC (P = 0.048), PTR (P = 0.008) and CST (P = 0.044). Baseline AWF values in CST significantly discriminated progressed from non-progressed patients (P = 0.021; area under the curve, 0.854). CONCLUSION: Based on its change over time and its relationship with disease progression, among the analyzed metrics, AWF seems the most sensitive metric of WM tissue damage in PP-MS and therefore it could be considered as a marker for monitoring disease progression.

An overview of osteopathy graduates' perceived preparedness at transition from educational environment to clinic environment one year after graduation: a cross sectional study.

BACKGROUND: This study investigated perceived preparedness to practice, one year after graduation across osteopathic education institutions (OEIs) and explored possible differences between countries where osteopathy is regulated (Reg) and countries where it is not (Unreg). METHODS: Two hundred forty-five graduates from 7 OEIs in 4 European countries, already assessed in a previous study, were contacted one year after their graduation to complete the survey. Survey tools included a questionnaire to assess perceived preparedness to practice: Association of American Medical Colleges (AAMC) questionnaire, and a questionnaire to collect socio-demographic information and practice characteristics. RESULTS: One hundred sixty-eight graduates (68.6%) completed the survey. The AAMC mean score one year after the graduation (23.19; confidence interval 22.81-23.58) was significantly higher than in the previous study (17.58; 16.90-18.26) (p < 0.001). A difference was also found between Reg (23.49; 23.03-23.95) and Unreg (22.34; 21.74-22.94) (p = 0.004). Osteopaths with a previous healthcare degree scored significantly higher on AAMC score (25.53; 24.88-26.19) than osteopaths without a previous healthcare degree (22.33; 21.97-22.69) (p < 0.001). Regulation and a previous degree were the only significant independent variables in the most predictive multivariate linear model. The model had an r2 = 0.33. CONCLUSIONS: Graduates from OEIs where osteopathy is regulated felt significantly better prepared to practice than Unreg. Systematic information searches about graduates' perception of preparedness to practice, may enable OEIs to strengthen their existing curricula to ensure their graduates are effectively prepared to practice.

Spread of dystonia in patients with idiopathic adult-onset laryngeal dystonia.

BACKGROUND AND PURPOSE: Adult-onset laryngeal dystonia (LD) can be isolated or can be associated with dystonia in other body parts. Combined forms can be segmental at the onset or can result from dystonia spread to or from the larynx. The aim of this study was to identify the main clinical and demographic features of adult-onset idiopathic LD in an Italian population with special focus on dystonia spread. METHODS: Data were obtained from the Italian Dystonia Registry (IDR) produced by 37 Italian institutions. Clinical and demographic data of 71 patients with idiopathic adult-onset LD were extracted from a pool of 1131 subjects included in the IDR. RESULTS: Fifty of 71 patients presented a laryngeal focal onset; the remaining subjects had onset in other body regions and later laryngeal spread. The two groups did not show significant differences of demographic features. 32% of patients with laryngeal onset reported spread to contiguous body regions afterwards and in most cases (12 of 16 subjects) dystonia started to spread within 1 year from the onset. LD patients who remained focal and those who had dystonia spread did not show other differences. CONCLUSIONS: Data from IDR show that dystonic patients with focal laryngeal onset will present spread in almost one-third of cases. Spread from the larynx occurs early and is directed to contiguous body regions showing similarities with clinical progression of blepharospasm. This study gives a new accurate description of LD phenomenology that may contribute to improving the comprehension of dystonia pathophysiology.

Correction to: The Italian Dystonia Registry: rationale, design and preliminary findings.

In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy.The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.

Looking into cognitive impairment in primary-progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment in primary-progressive multiple sclerosis (PP-MS) is correlated with global brain atrophy. Unfortunately, brain volume computation requires processing resources that are not widely available in clinical practice. Therefore, we decided to test the predictive role of retinal atrophy metrics on cognitive decline, applying them as a proxy of gray matter atrophy in PP-MS. METHODS: Twenty-five patients with PP-MS completed the Brief International Cognitive Assessment for Multiple Sclerosis and underwent spectral-domain optical coherence tomography (OCT) and 3.0-T magnetic resonance imaging. We tested, through a stepwise logistic regression, whether OCT metrics [retinal nerve fiber layer, ganglion cell + inner plexiform layer (GCIPL) and total macular volume] predicted cognitive impairment and explored the role of gray matter atrophy in mediating these correlations. RESULTS: Among OCT metrics, only GCIPL was associated with cognitive impairment (rp = 0.448, P = 0.036) and predictive of objective cognitive impairment (Wald [1] = 4.40, P = 0.036). Controlling for demographics, normalized brain volume and thalamic volume were correlated with GCIPL (rp = 0.427, P = 0.047 and rp = 0.674, P = 0.001, respectively) and cognitive scores (rp = 0.593, P = 0.004 and rp = 0.501, P = 0.017, respectively), with thalamic volume nearly mediating the association between GCIPL and cognition (Sobel z = 1.86, P = 0.063). CONCLUSIONS: The GCIPL thickness is a suitable measure of neurodegeneration. In comparison with brain atrophy, GCIPL offers higher histopathological specificity, being a pure correlate of neuronal loss, and may be a non-invasive, easy-to-perform way to quantitatively evaluate and monitor neuronal loss related to cognitive impairment in PP-MS.

The Italian Dystonia Registry: rationale, design and preliminary findings.

The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

Upper motor neuron evaluation in multiple sclerosis patients treated with Sativex®.

BACKGROUND: Spasticity in multiple sclerosis (MS) results from an imbalance of inputs from descending pathways to the spinal motor circuits, as well as from a damage of the corticospinal tract (CST). OBJECTIVES: To assess CST impairment in MS patients with and without spasticity and to evaluate its evolution under Sativex® treatment. METHODS: Ten MS patients with spasticity ("cases") underwent clinical (EDSS, 9-hole Peg, Ashworth scale, Timed 25-Foot Walk, and NRS for spasticity), MRI (CST fractional anisotropy [FA]), and electrophysiological (central motor conduction time [CMCT] and H/M ratio) evaluations at baseline and after 12 months. We selected 20 MS patients without spasticity as control group at baseline. RESULTS: At baseline, cases showed a lower CST FA (0.492±0.045 vs 0.543±0.047; P=.01) and a higher CMCT (P=.001) compared to the control group. No correlations were found between clinical, electrophysiological, and MRI features. After 12 months, cases showed a decrease in non-prevalent degree of impairment (PDI) side FA (0.502±0.023 vs 0.516±0.033; P=.01) without differences for electrophysiological features compared to baseline. Treatment with Sativex® resulted in a reduction of NRS for spasticity (P=.01). CONCLUSIONS: We confirm the presence of CST impairment in MS patients with spasticity. We did not identify structural/electrophysiological correlates that could explain Sativex® clinical effect.

Imported occupational lead poisoning: report of four cases.

BACKGROUND: In most industrialized countries, occupational lead poisoning has become increasingly rare, however this metal remains a serious health hazard in the rest of the world. REPORT OF CASES: We observedfour male patients (aged 35 / 54 years) who had suffered recurrent abdominal pain due to recent lead exposure (for 7 to 13 months) in two Chinese battery recycling plants. On their return to Italy, three of them presented normocytic, normochromic anaemia. The diagnosis was confirmed by high lead levels in the blood and urine, decreased erythrocyte delta-aminolevulinic acid dehydratase (ALA-D), raised erythrocyte zinc protoporphyrin (ZP), and elevated urinary excretion of b-aminolevulinic acid (ALA-U) and porphyrins. Chelation with EDTA resulted in increased urinary lead excretion, improvement of the clinical picture, decreased ZP, and progressive normalization of the other lead biomarkers (Pb-B, ALA-D, ALA-U, urinary porphyrins). CONCLUSIONS: Temporary work in developing countries may result in imported lead poisoning. Differential diagnosis of this unusual condition requires careful medical history collection and specific toxicological analysis. Preventive measures for workers going abroad are needed.

National Cholesterol Education Program and International Diabetes Federation definitions of metabolic syndrome in the prediction of diabetes. Results from the FIrenze-Bagno A Ripoli study.

BACKGROUND: The International Diabetes Federation (IDF) proposed to modify the diagnostic criteria for metabolic syndrome (MS) previously issued by the National Cholesterol Education Program (NCEP). Aim of the present investigation is to compare the predictive value for diabetes of NCEP and IDF definitions of MS in a large sample of predominantly Caucasian subjects. METHODS: A prospective observational study was performed on a cohort study (n = 3096) enrolled in a diabetes-screening programme, the FIrenze-Bagno A Ripoli study. All subjects with fasting glucose >126 mg/dl and/or post-load glucose > or =200 mg/dl (5.7%) were excluded from the present analysis. Follow-up of each subject was continued until diagnosis of diabetes, death or until 31 December 2005. Mean follow-up was 27.7 +/- 11.3 months. RESULTS: Among subjects enrolled, 13.7 and 25.2% were affected by MS using NCEP and IDF criteria respectively. During follow-up, 38 new cases of diabetes were diagnosed, with a yearly incidence rate of 0.5%. The relative risk for diabetes in subjects with MS was 10.10 [5.13; 20.00] and 7.87 [3.70; 16.7] using NCEP and IDF definitions respectively. After adjustment for age, sex, fasting glucose and waist circumference, NCEP-defined MS, but not IDF-, was significantly associated with incident diabetes (hazard ratio, 95% CI: 2.41 [1.01; 5.95] and 2.05 [0.80; 5.29] respectively). CONCLUSIONS: Although the reasons for the proposed changes in diagnostic criteria for MS are easily understandable, the newer IDF definition, while increasing estimates of prevalence of the syndrome, reduces the effectiveness of MS in identifying subjects at risk for diabetes. Further research is needed before the previous NCEP criteria are abandoned.

Effects of metformin on glucagon-like peptide-1 levels in obese patients with and without Type 2 diabetes.

Metformin has been shown to increase glucagon-like peptide-1 (GLP-1) levels after an oral glucose load in obese non-diabetic subjects. In order to verify if this effect of the drug was also present in obese Type 2 diabetic patients who have never been treated with hypoglycemic drugs, 22 Type 2 diabetic and 12 matched non-diabetic obese patients were studied. GLP-1 was measured before and after a 100 g glucose load at baseline, after a single oral dose of 850 mg of metformin, and after 4 weeks of treatment with metformin 850 mg three times daily. Post-load GLP-1 levels were significantly lower in diabetic patients. A single dose of metformin did not modify GLP-1 levels. After 4 weeks of treatment, fasting GLP-1 increased in diabetic patients (3.8 vs 4.9 pmol/l; p<0.05), while the incremental area under the curve of GLP-1 significantly increased in both diabetic [93.6 (45.6-163.2) vs 151.2 (36.0-300.5) pmol x min/l; p<0.05] and non-diabetic [187.2 (149.4-571.8) vs 324.0 (238.2-744.0) pmol x min/l; p<0.05] subjects. In conclusion, GLP-1 levels after an oral glucose load in obese type 2 diabetic patients were increased by 4 weeks of metformin treatment in a similar fashion as in obese subjects with normal glucose tolerance.