Development and validation of the Myasthenia Gravis TeleScore (MGTS).

OBJECTIVE: The aim of our study was to validate the Myasthenia Gravis TeleScore (MGTS), a scale for the evaluation of MG patients in telemedicine. INTRODUCTION: COVID-19 pandemic has boosted telemedicine in clinical practice. It could be crucial in the care of neurological patients with chronic disease. However, there is a lack of validated disease-specific tools to evaluate MG patients in telemedicine. METHODS: The MGTS included ten items divided in four districts: ocular, generalized muscular strength, bulbar, and respiratory. Patients were assessed with two different scales: the MGTS and the INCB-MG chosen as a reference from which MGTS was partially derived. Visit in presence with INCB-MG and televisit with MGTS were performed consecutively. Televisit was conducted by another neurologist between two rooms. A blind method was adopted. The strength of correlation was determined by the correlation coefficient (r); analysis of covariance (ANOVA-Kruskal-Wallis test) was used to compare subgroups. Significance was set to p < 0.05. RESULTS: One hundred thirty-one patients were included in the study, 71 females and 60 males. The Spearman correlation coefficient between the INCB-MG scale and the MGTS was 0.825 (p < 0.001), indicating a very strong correlation between them. Different items showed different correlations from low to high (0.32 to 0.80). As expected, correlation was lower between items with different evaluation modality (anamnestic vs clinical). DISCUSSION: The MGTS demonstrated a good correlation with INCB-MG, reliability and construct validity.

Prevalence of low back pain and its effect on health-related quality of life in 409 scholar adolescents from the Veneto region.

Low back pain (LBP) is a common condition with profound effects on well-being. We aimed to define the prevalence and the characteristics of LBP and to investigate its impact on the quality of life (QoL) of 409 students (265 females and 144 males), all high-school adolescents from the Veneto region. LBP was measured with a structured, self-report questionnaire, while the SF-36 questionnaire was used to measure physical and mental QoL. 253 students (61.3%) reported one or more episodes of LBP, with female predominance. Adolescents with LBP treated with drugs and rehabilitation cares have significantly poor belief in pain resolution (p=0.005), but more belief in a prevention program (p=0.006) than the others. After adjustment for sex, a significant association between the SF-36 dimension of vitality and the presence of LBP in males was observed. All SF-36 domains except mental health were significantly higher in females with LBP. Our study confirmed that LBP is frequent in Italian scholar adolescents and has an impact on QoL. Strategies for reducing the effects of LBP on QoL should be an important purpose for clinicians and health policy makers.

Anti-sulfatide/galactocerebroside antibodies in immunoglobulin M paraproteinemic neuropathies.

BACKGROUND AND PURPOSE: Anti-sulfatide antibodies have been observed in heterogeneous neuropathies and their clinical relevance is still controversial. Whether the combination of sulfatide with galactocerebroside would increase sensitivity or specificity of enzyme-linked immunosorbent assay testing compared to sulfatide alone was assessed. METHODS: Immunoglobulin M (IgM) antibodies to sulfatides, galactocerebroside and combined sulfatide and galactocerebroside (Sulf/GalC) were measured in 229 neuropathy patients, including 73 with IgM paraproteinemic neuropathy [62 with anti-myelin-associated glycoprotein (anti-MAG) antibody] and 156 with other neuropathies. Results from 27 patients with IgM monoclonal gammopathy without neuropathy and 28 healthy subjects served as control. RESULTS: Thirty-three patients showed increased titers of anti-sulfatide antibodies, 28 of whom had an IgM paraproteinemic neuropathy (P < 0.0001). When evaluating the reactivity for the combination Sulf/GalC, 57/229 patients were found to be positive, including 36/73 (49%) with IgM paraproteinemic neuropathy (P < 0.0001). Patients with known anti-sulfatide antibodies also showed anti-Sulf/GalC reactivity, with increased titers in 48.5% of the cases. Testing for anti-Sulf/GalC antibodies allowed 24 additional patients to be detected (eight with IgM paraproteinemic neuropathies), who had no reactivity to the individual glycolipids. Amongst the 11 subjects with IgM paraproteinemic neuropathy who were negative for anti-MAG antibodies, only two were reactive to sulfatide, whilst six (55%) were found to be positive when tested against the combination of sulfatide and galactocerebroside. CONCLUSIONS: Testing for both sulfatide and galactocerebroside in IgM paraproteinemic neuropathies seems to increase the sensitivity compared to anti-sulfatide antibodies alone (49% and 39%, respectively, with a slightly reduced specificity, from 97% to 87%), helping the characterization of otherwise undefined neuropathy that could benefit from immunomodulatory therapy.

Neuroimaging Changes in Menkes Disease, Part 1.

Menkes disease is a rare multisystem X-linked disorder of copper metabolism. Despite an early, severe, and progressive neurologic involvement, our knowledge of brain involvement remains unsatisfactory. The first part of this retrospective and review MR imaging study aims to define the frequency rate, timing, imaging features, and evolution of intracranial vascular and white matter changes. According to our analysis, striking but also poorly evolutive vascular abnormalities characterize the very early phases of disease. After the first months, myelination delay becomes evident, often in association with protean focal white matter lesions, some of which reveal an age-specific brain vulnerability. In later phases of the disease, concomitant progressive neurodegeneration might hinder the myelination progression. The currently enriched knowledge of neuroradiologic finding evolution provides valuable clues for early diagnosis, identifies possible MR imaging biomarkers of new treatment efficacy, and improves our comprehension of possible mechanisms of brain injury in Menkes disease.

BAFF Index and CXCL13 levels in the cerebrospinal fluid associate respectively with intrathecal IgG synthesis and cortical atrophy in multiple sclerosis at clinical onset.

BACKGROUND: B lymphocytes are thought to play a relevant role in multiple sclerosis (MS) pathology. The in vivo analysis of intrathecally produced B cell-related cytokines may help to clarify the mechanisms of B cell recruitment and immunoglobulin production within the central nervous system (CNS) in MS. METHODS: Paired cerebrospinal fluid (CSF) and serum specimens from 40 clinically isolated syndrome suggestive of MS or early-onset relapsing-remitting MS patients (CIS/eRRMS) and 17 healthy controls (HC) were analyzed for the intrathecal synthesis of IgG (quantitative formulae and IgG oligoclonal bands, IgGOB), CXCL13, BAFF, and IL-21. 3D-FLAIR, 3D-DIR, and 3D-T1 MRI sequences were applied to evaluate white matter (WM) and gray matter (GM) lesions and global cortical thickness (gCTh). RESULTS: Compared to HC, CIS/eRRMS having IgGOB (IgGOB+, 26 patients) had higher intrathecal IgG indexes (p < 0.01), lower values of BAFF Index (11.9 ± 6.1 vs 17.5 ± 5.2, p < 0.01), and higher CSF CXCL13 levels (27.7 ± 33.5 vs 0.9 ± 1.5, p < 0.005). In these patients, BAFF Index but not CSF CXCL13 levels inversely correlated with the intrathecal IgG synthesis (r > 0.5 and p < 0.05 for all correlations). CSF leukocyte counts were significantly higher in IgGOB+ compared to IgGOB- (p < 0.05) and HC (p < 0.01), and correlated to CSF CXCL13 concentrations (r 0.77, p < 0.001). The gCTh was significantly lower in patients with higher CSF CXCL13 levels (2.41 ± 0.1 vs 2.49 ± 0.1 mm, p < 0.05), while no difference in MRI parameters of WM and GM pathology was observed between IgGOB+ and IgGOB-. CONCLUSIONS: The intrathecal IgG synthesis inversely correlated with BAFF Index and showed no correlation with CSF CXCL13. These findings seem to indicate that intrathecally synthesized IgG are produced by long-term PCs that have entered the CNS from the peripheral blood, rather than produced by PCs developed in the meningeal follicle-like structures (FLS). In this study, CXCL13 identifies a subgroup of MS patients characterized by higher leukocyte counts in the CSF and early evidence of cortical thinning, further suggesting a role for this chemokine as a possible marker of disease severity.

Basilar Artery Changes in Fabry Disease.

BACKGROUND AND PURPOSE: Dolichoectasia of the basilar artery is a characteristic finding of Fabry disease. However, its prevalence, severity, and course have been poorly studied. This study quantitatively evaluated, by MRA, a panel of basilar artery parameters in a large cohort of patients with Fabry disease. MATERIALS AND METHODS: Basilar artery mean diameter, curved length, "origin-to-end" linear distance (linear length), and tortuosity index ([curved length ÷ linear length] - 1) were retrospectively measured on 1.5T MRA studies of 110 patients with Fabry disease (mean age, 39.4 ± 18.6 years; 40 males) and 108 control patients (mean age, 42.0 ± 18.2 years; 40 males). RESULTS: Patients with Fabry disease had increased basilar artery mean diameter (P < .001) and basilar artery linear length (P = .02) compared with control patients. Basilar artery curved length and tortuosity index correlated with age in both groups (P < .001), whereas basilar artery linear length correlated with age only in patients with Fabry disease (P = .002). Patients with Fabry disease showed a basilar artery curved length mean increase of 4.2% (9.7% in male patients with Fabry disease versus male control patients), whereas the basilar artery mean diameter had a mean increase of 12.4% (14.3% in male patients with Fabry disease versus male control patients). Male patients with Fabry disease had increased basilar artery mean diameter, curved length, and tortuosity index compared with female patients with Fabry disease (P = .04, P = .02, and P < .001, respectively) and male control patients (P < .001, P = .01, and P = .006, respectively). Female patients with Fabry disease demonstrated an age-dependent increase of basilar artery mean diameter that became significant (P < .001) compared with female control patients above the age of 45 years. CONCLUSIONS: The basilar artery of patients with FD is subjected to major remodeling that differs according to age and sex, thus providing interesting clues about the pathophysiology of cerebral vessels in Fabry disease.

Image-guided fine-needle aspiration cytology and flow cytometry phenotyping of neck lymphadenopathy for the diagnosis of recurrent lymphoma.

OBJECTIVE: In patients with a history of lymphoma, each lymphadenopathy should be carefully evaluated. The aims of this study were to evaluate (i) the usefulness of high-resolution ultrasonography (US), US-guided fine-needle aspiration cytology (FNAC) and flow cytometry phenotyping (FCP) together in the diagnosis of recurrent lymphoma and (ii) whether these tools were independent predictors of correct results. DESIGN: Retrospective cohort study with stepwise forward logistic regression analysis of results. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 151 patients with a history of lymphoma who developed a cervical mass during follow-up. METHODS: On neck US, a lymphadenopathy was shown in 129 (85.4%) patients (median age 57 years, range 18-78 years), and US-guided FNAC combined with FCP were immediately performed. All patients had surgical excision and subsequent histological examination of the enlarged node(s), to establish lymphoma subclassification. RESULTS: Final histology confirmed recurrence in 82 (63.6%) patients. According to the logistic regression analysis, FNAC and FCP were independent predictors of correct results (P = 0.009 and 0.028, respectively) and did not interfere with each other. The sensitivity, specificity and accuracy of the combination of all of the tools were 98.8%, 100% and 99.2%, respectively, and the area under the receiver operating characteristic curve was 0.902 (95% CI: 0.797-0.986). CONCLUSION: This minimally invasive procedure is easily performed and should be recommended for all patients with cervical lymphadenopathy and a history of lymphoma, avoiding the need of core-biopsy or surgical excision if recurrence was excluded.

No effect of AR polyG polymorphism on spinal and bulbar muscular atrophy phenotype.

BACKGROUND AND PURPOSE: Disease severity varies considerably among patients with Spinal and Bulbar Muscular Atrophy (SBMA). Our aim was to investigate the role of androgen receptor (AR) polymorphic repeats in SBMA phenotype. METHODS: We analyzed the length of AR polyQ and polyG tracts in 159 SBMA patients. RESULTS: No relationship between polyG size or polyG/polyQ haplotypes and clinical phenotype was found. An independent negative correlation between polyQ-length and onset of weakness was confirmed (P < 0.001). CONCLUSIONS: The negative results of our study prompt to continue the search for potential disease modifiers in SBMA outside the AR gene.

Accuracy of transcranial brain parenchyma sonography in the diagnosis of dementia with Lewy bodies.

BACKGROUND AND PURPOSE: Transcranial sonography (TCS) of the brain parenchyma is used to visualize alterations in the substantia nigra (SN) and it is applied for early diagnosis of Parkinson's disease. Our aim was to explore specific echogenic alterations of the SN in dementia with Lewy bodies (DLB) compared to Alzheimer's disease (AD). METHODS: Seventy-one subjects underwent TCS: 22 DLB, 28 AD and 21 healthy elderly controls. Cognitive impairment, extrapyramidal signs, visual hallucinations, fluctuations and rapid eye movement sleep behaviour symptoms were investigated. TCS assessed SN hyperechogenicity and symmetry. RESULTS: Transcranial sonography revealed SN hyperechogenicity in 100% of DLB compared to 50% of AD and 30% of controls. Mean SN echogenic area (cm(2) ) was 0.22 ± 0.03 in DLB, 0.15 ± 0.03 in AD and 0.14 ± 0.03 in controls (P < 0.0001). More than 50% of DLB presented a marked hyperechogenicity (cutoff value >0.22 cm(2) ) compared to only 10% of AD (P < 0.0003). DLB had symmetrical SN enlargement, whereas AD were mostly asymmetrical (P = 0.015). A combination of SN echogenic area and asymmetry index had a sensitivity of 88.9% and a specificity of 81.2% in discriminating DLB from AD (positive predictive value 85.7%, negative predictive value 85.7%). No association was found between SN hyperechogenicity and Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination or the presence of visual hallucinations. CONCLUSIONS: Transcranial sonography may be a valid supportive tool in the diagnostic workup of neurodegenerative dementia helping clinicians to distinguish DLB from AD even at the early stages.

Power spectral analysis of two-channel EEG in very premature infants undergoing heat loss prevention.

OBJECTIVE: To evaluate whether wearing a wool cap, a routine practice used to prevent heat loss in premature infants, affects interpretation of electroencephalogram spectral analysis. METHODS: Eighteen premature infants (median gestational age 28 weeks, range 23-32) without neurological complications were randomized to two channel (C3, C4 referred to Cz) digital electroencephalogram recordings with (90 min) and without (90 min) wearing wool cap, at 4 days of life. Electroencephalogram was analyzed automatically by measurement of burst suppression ratio and asymmetry index and by Fast Fourier Transform to calculate total absolute spectral power; relative spectral power in the δ (0.5-3.5 Hz), θ (4-7.5 Hz), α (8-12.5 Hz), and ß (13-30 Hz) frequency bands; spectral edge frequency; and mean dominant frequency. RESULTS: The use of wool cap had no effect on all electroencephalogram parameters considered. Gestational age showed an effect on relative spectral power of all considered bands, spectral edge frequency and mean dominant frequency, while no effect was seen on burst suppression ratio and asymmetry index. Neonates born at gestational weeks lower than 28 had significantly higher relative power in the δ band and lower relative power in the α and ß bands. CONCLUSIONS: Heat loss prevention using wool cap does not affect interpretation of spectral electroencephalogram. Spectral values in our group of very premature infants without neurological complications correspond to normal data reported in the literature. Maturation changes consist of reduction of relative power of the δ band, spectral edge frequency and mean dominant frequency.