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.

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.

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.

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.

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.

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.

Ultrasound assessment of oxaliplatin-induced neuropathy and correlations with neurophysiologic findings.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy is a major adverse effect of oxaliplatin (OXL) treatment. Whereas neurophysiologic study is commonly used to assess the occurrence and severity of polyneuropathies, ultrasound (US) analysis of the peripheral nerves, an emerging technique in the study of peripheral nerve diseases, has never been used in chemotherapy-induced peripheral neuropathy. PATIENTS AND METHODS: Fifteen patients (four women; 11 men; mean age, 60.1 ± 10.6 years; median, 62; range, 37-75) with colorectal cancer treated with OXL-based treatment have been clinically and neurophysiologically evaluated before and after OXL therapy. At the end of chemotherapy, all patients underwent also nerve US study at four limbs, and the findings correlated with clinical and neurophysiologic measures. RESULTS: Clinical and neurophysiological evaluation showed that 13 of 15 (86.7%) patients developed sensory axonal neuropathy, 10 of whom severe (two or more sensory nerve action potential amplitude absent and the other amplitudes decreased of ≥50%). Nerve US did not reveal decreased cross-sectional area (CSA), a reported finding in axonal neuropathies. Instead increased CSA at entrapment sites (median nerve at wrist and ulnar nerve at elbow) was found in 09/15 (60%) of patients. DISCUSSION: Sensory axonal neuropathy is a very common complication of OXL therapy, affecting almost 90% of patients. US findings of enlargement of median and ulnar nerves, mostly at entrapment sites, in patients with no history or symptoms of neuropathies at recruitment, and no neurophysiologic evidence of entrapment, may be expression of increased, OXL-induced, nerve susceptibility to mechanical damage. An ongoing prospective study will help clarify these findings.

Ambulatory arterial stiffness indices and non-alcoholic fatty liver disease in essential hypertension.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) has been found to be strongly related to an increased arterial stiffness in patients with essential hypertension, suggesting a pathophysiologic link between major cardiovascular and metabolic abnormalities associated with liver steatosis and the functional and structural alterations of the arterial wall. The aim of our study was to investigate, in a group of essential hypertensive patients without additional cardiovascular risk factors, the relationship between NAFLD and arterial stiffness. METHODS AND RESULTS: Sixty-eight consecutive patients with essential hypertension underwent 24-h ambulatory blood pressure monitoring (ABPM) and were separated according to the presence (n = 40) or absence (n = 28) of NAFLD at liver ultrasonography. The Ambulatory Arterial Stiffness Index (AASI) and Symmetric AASI (Sym-AASI) were derived from ABPM tracings. Patients with diabetes, obesity, hyperlipidaemia or other risk factors for cardiovascular or liver disease were excluded. Hypertensive patients were compared with a normotensive control group.The two hypertensive groups had comparable age, sex distribution and clinic/ABPM blood pressure levels. In hypertensive patients with NAFLD, body mass index, fasting glucose, insulin, homeostasis model of assessment of insulin resistance index and triglyceride levels were higher, whereas plasma adiponectin was lower than in patients without NAFLD. In hypertensive patients, AASI and Sym-AASI were higher (P < 0.001) than in normotensive subjects, but both indices of vascular stiffness were comparable in patients with and without NAFLD. CONCLUSIONS: In essential hypertensive patients without additional cardiovascular risk factors, NAFLD is associated with insulin resistance but not with increased arterial stiffness.

Genetic variation in KIFAP3 is associated with an upper motor neuron-predominant phenotype in amyotrophic lateral sclerosis.

BACKGROUND: Some authors have recently reported that the CC genotype of single-nucleotide polymorphism (SNP) rs1541160 mapping within the kinesin-associated protein 3 (KIFAP3) gene is associated with increased survival in sporadic amyotrophic lateral sclerosis (sALS). OBJECTIVE AND METHODS: The relationship between the rs1541160 genotype and several clinical features of 228 ALS patients was evaluated with the intent of assessing any association between the ALS phenotype and KIFAP3. The SNP rs1541160 within the KIFAP3 expression profile was investigated using real-time PCR in a group of 6 patients harboring the CC genotype and in 12 patients harboring the TT genotype. RESULTS: Analysis of our patients' clinical features showed that almost half of those with the CC genotype were classified as having upper motor neuron-predominant ALS (UMN-ALS). Conversely, there was an approximately 10% frequency of UMN-ALS in both the TT and the TC patient groups as well as in the entire cohort considered as a whole (p < 0.005). The SNP rs1541160 genotype did not appear to have any effect on patient survival or on KIFAP3 expression. CONCLUSIONS: The incidence of the UMN-ALS phenotype in the CC patients of this cohort supports the hypothesis that the SNP rs1541160 within the KIFAP3 gene is a potential modifier of the ALS phenotype.

Retrospective study on PET-SPECT imaging in a large cohort of myotonic dystrophy type 1 patients.

The aim was to study brain involvement in myotonic dystrophy type 1 by single photon emission tomography (SPECT) and positron emission tomography (PET). 58 DM1 patients were subjected to SPECT; 17 to both SPECT and PET. SPECT patients were grouped as 'normally perfused' and 'abnormally perfused'; PET patients as 'normal performers' and 'abnormal performers'. To quantify hypoperfusion and/or hypometabolism, we used a semi-quantitative scale. To localize focal hypoperfusion/hypometabolism, nine cerebral areas of involvement were identified. The Chi-square, Wilcoxon, McNemar tests were used for statistics. SPECT showed abnormalities in 52/58 patients. PET showed an abnormal glucidic uptake in 15/17. Hypoperfusion was mild/moderate in 50/58 patients, mostly involving the left supratentorial areas. Abnormal glucidic uptake was mainly observed in the left frontal lobe. Abnormalities in blood perfusion and/or glucose metabolism are frequent in DM1. These abnormalities involve the left more often than the right hemisphere, the frontal lobe more than other lobes. Such abnormalities are more often cortical than subcortical.

Transverse dural sinuses: incidence of anatomical variants and flow artefacts with 2D time-of-flight MR venography at 1 Tesla.

PURPOSE: This study sought to identify imaging criteria useful in discriminating anatomical variants from thrombosis of the posterior intracranial venous system. MATERIALS AND METHODS: A total of 102 patients underwent coronal unenhanced two-dimensional time-of-flight (2D ToF) magnetic resonance (MR) venography. Transverse sinus (TS) calibre and asymmetry were considered. Oval (O-FG) and linear (L-FG) flow gaps were recorded. Several slices of the 2D ToF sequence were applied perpendicularly to the TS within each FG to avoid in-plane saturation. RESULTS: Mean calibre of the right TS was significantly greater than the contralateral sinus (6.5 mm+/-1.84 vs 5.1 mm+/-1.72). Right and left dominance was observed in 61% and 17% of cases, respectively. The mean right-left TS diameter was 5.77 mm. Among 204 TS, 44 L-FG and 42 O-FG were observed. Partial L-FG (<2/3 of TS) never involved the distal TS. No L-FG was observed in a dominant TS. Supplementary sagittal 2D ToF images disclosed blood flow in all but two L-FGs. O-FGs were mostly observed laterally (91%). CONCLUSIONS: L-FGs in a dominant TS, partial L-FGs in the distal part or O-FG in the medial part of any TS, a left-right mean diameter <3 mm and absence of flow even in ToF images perpendicular to the direction of blood flow should raise the suspicion of sinus pathology.

Neurolupus is associated with anti-ribosomal P protein antibodies: an inception cohort study.

OBJECTIVE: Serum IgG antibodies (Abs) to phosphorylated ribosomal (P ribosomal) proteins have been inconsistently associated with neuropsychiatric manifestations in systemic lupus erythematosus (SLE). Our aim was to assess whether serum IgG Abs to ribosomal P proteins are associated with neuropsychiatric SLE. PATIENTS AND METHODS: We examined an inception cohort of 219 SLE patients. Neuropsychiatric SLE manifestations were characterized using the American College of Rheumatology (ACR) definition. Serum Abs to P ribosomal proteins were searched for by immunoblotting. In a subgroup of patients, Abs were investigated also in cerebrospinal fluid (CSF). RESULTS: Abs to P ribosomal proteins were detected in 45 (21%) patients, 23 of whom (51%) with neuropsychiatric involvement. Abs to P ribosomal protein were present both in serum and CSF. Abs to P ribosomal proteins significantly correlated with psychosis (p=0.017), mononeuropathy multiplex (p=0.040), malar rash (p=0.004), serum anti-Sm Abs (p=0.042), and lupus anticoagulant (p=0.036). SLE onset age was significantly younger in patients with Abs to P ribosomal proteins. Logistic regression analysis confirmed the relationship between Abs to P ribosomal proteins and psychosis, malar rash, SLE onset age and lupus anticoagulant. CONCLUSIONS: Abs to ribosomal P proteins are associated with psychosis and might be associated with peripheral nervous system complications.

Non-alcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in essential hypertension.

BACKGROUND AND AIM: Insulin resistance is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). A relation between insulin sensitivity and left ventricular morphology and function has been reported in essential hypertension, where a high prevalence of NAFLD has been recently found. We investigated the inter-relationship between left ventricular morphology/function, metabolic parameters and NAFLD in 86 never-treated essential hypertensive patients subdivided in two subgroups according to the presence (n = 48) or absence (n = 38) of NAFLD at ultrasonography. METHODS AND RESULTS: The two groups were similar as to sex, age and blood pressure levels. No patient had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for liver disease. Body mass index, waist circumference, triglycerides, glucose, insulin, homeostasis model of assessment index for insulin resistance (HOMA-IR), aspartate aminotransferase and alanine aminotransferase were higher and adiponectin levels were lower in patients with NAFLD than in patients without NAFLD, and were associated with NAFLD at univariate analysis. Patients with NAFLD had similar prevalence of left ventricular hypertrophy compared to patients without NAFLD, but a higher prevalence of diastolic dysfunction (62.5 vs 21.1%, P < 0.001), as defined by E/A ratio <1 and E-wave deceleration time >220 ms. Diastolic dysfunction (P = 0.040) and HOMA-IR (P = 0.012) remained independently associated with NAFLD at backward multivariate analysis. CONCLUSIONS: Non-alcoholic fatty liver disease was associated with insulin resistance and abnormalities of left ventricular diastolic function in a cohort of patients with essential hypertension, suggesting a concomitant increase of metabolic and cardiac risk in this condition.

Thalidomide and sensory neurotoxicity: a neurophysiological study.

BACKGROUND: Recent studies confirmed a high incidence of sensory axonal neuropathy in patients treated with different doses of thalidomide. The study's aims were to measure variations in sural nerve sensory action potential (SAP) amplitude in patients with refractory cutaneous lupus erythematosus (CLE) treated with thalidomide and use these findings to identify the neurotoxic potential of thalidomide and the recovery capacity of sensory fibres after discontinuation of treatment. PATIENTS AND METHODS: Clinical and electrophysiological data in 12 female patients with CLE during treatment with thalidomide and up to 47 months after discontinuation of treatment were analysed. Sural nerve SAP amplitude reduction > or =40% was the criteria for discontinuing therapy. RESULTS: During treatment, 11 patients showed a reduction in sural nerve SAP amplitude compared to baseline values (9 with a reduction > or =50% and 2 <50%). One patient showed no changes in SAP amplitude. Five patients complained of paresthesias and leg cramps. After thalidomide treatment, sural SAP amplitude recovered in 3 patients. At detection of reduction in sural nerve SAP amplitude, the median thalidomide cumulative dose was 21.4 g. The threshold neurotoxic dosage is lower than previously reported. CONCLUSIONS: Sural nerve SAP amplitude reduction is a reliable and sensitive marker of degeneration and recovery of sensory fibres. This electrophysiological parameter provides information about subclinical neurotoxic potential of thalidomide but is not helpful in predicting the appearance of sensory symptoms.

Reliability of hearing screening in high-risk neonates: comparative study of otoacoustic emission, automated and conventional auditory brainstem response.

OBJECTIVE: To compare the diagnostic reliability of automated transient evoked otoacoustic emissions (a-TEOAE), automated auditory brainstem response (a-ABR) and conventional brainstem auditory evoked potential (BAEP/ABR) for identification of hearing loss in high-risk neonates. METHODS: Two hundred and six neonatal intensive care unit (NICU) admitted neonates were tested pre-discharge. Follow-up included a-TEOAE in all children, repetition of a-ABR or BAEP if failed in NICU. Sensitivity and specificity were compared and correlated with auditory risk factors. RESULTS: BAEP had the highest sensitivity (100%) and specificity (90.8%), a-ABR the lowest (88.9% and 70.6%). A statistically significant difference in risk factors for temporary hearing loss was observed between normal and false positive a-TEOAE and BAEP, but not a-ABR outcome. Differences in specificity between a-ABR and a-TEOAE explain the pattern of "absent a-ABR/present a-TEOAE" in 13.8% of ears. CONCLUSIONS: The BAEP appears the more reliable test for hearing screening of high-risk neonates because of highest sensitivity and specificity and should be used to confirm the diagnosis of "auditory neuropathy" in high-risk neonates. The reliability of a-ABR devices in critically ill neonates needs further investigation. SIGNIFICANCE: This is, to our knowledge, the first attempt to compare the diagnostic reliability of a-TEOAE, a-ABR and BAEP in high-risk neonates.

Serum lipoprotein profile and APOE genotype in Alzheimer's disease.

Alterations in cholesterol homeostasis are associated with Alzheimer's disease (AD). The role played by specific fractions of serum lipoproteins in modifying the risk of AD, and the interaction with APOE genotype has not yet been investigated. We studied serum lipoprotein profiles using a gradient-density ultracentrifugation method in a cohort of late-onset sporadic AD patients without cerebrovascular lesions and in healthy elderly subjects. In the AD group the lipoprotein cholesterol distribution showed an increase in LDL cholesterol, reaching a significant difference with respect to controls in the LDL sub-fractions representing the transition between small dense-LDL (fraction 11, p = 0.04) and normal-density LDL particles (fraction 12, p = 0.03). APOE genotype and LDL cholesterol were independently associated with AD. The mean concentration of LDL in fractions 11 and 12 increased the risk of developing AD (p = 0.01 and p = 0.025, respectively). These results confirm that an alteration of cholesterol homeostasis is associated with AD and that serum concentrations of LDL cholesterol are higher in AD patients without cerebrovascular pathology than in elderly normal subjects. The presence of the APOE epsilon4+ allele is a risk factor for AD independent of increased serum cholesterol or a modification of other vascular risk factors. Increased levels of specific sub-fractions of LDL cholesterol may be associated with increased risk of AD.

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.

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.

The glucocorticoid receptor N363S polymorphism and steroid response in Duchenne dystrophy.

BACKGROUND: Steroid administration is beneficial in Duchenne muscular dystrophy (DMD), but the response, incidence, and the severity of side effects are variable. AIMS: To investigate whether glucocorticoid receptor (GRL) gene polymorphisms may be responsible for glucocorticoid sensitivity in DMD. METHODS: Forty eight DMD patients treated either with prednisone or deflazacort were subjected to genetic analyses of the GRL gene. RESULTS: Mutation studies revealed an heterozygous A to G mutation at GRL cDNA position 1220 in three DMD patients resulting in an asparagine to serine amino acid change at amino acid position 363 (N363S). The N363S carrier DMD patients showed a trend towards a later age at loss of ambulation in comparison with non-carrier patients. CONCLUSIONS: These data suggest that the N363S GRL polymorphism may be implicated in the long term response to glucocorticoids.