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Spontaneous canalith jam is an uncommon form of benign paroxysmal positional vertigo mimicking acute vestibular neuritis. We described for the first time a spontaneous horizontal semicircular canalith jam associated with a typical canalolithiasis involving contralateral posterior semicircular canal (PSC), illustrating how the latter condition modified direction-fixed nystagmus during head movements. An 81-year-old woman with persistent vertigo referred to our center. Video-Frenzel examination showed horizontal direction-fixed right-beating nystagmus in primary gaze position, inhibited by visual fixation. She exhibited corrective saccades after leftward head impulses. Chin-to-chest positioning at the head-pitch test did not modify spontaneous nystagmus, whereas slight torsional components with the top pole of the eye beating toward the right ear appeared in backward head-bending, resulting in mixed horizontal-torsional nystagmus. At supine positioning tests, direction-fixed nystagmus turned into direction-changing geotropic horizontal nystagmus, which was stronger on the left side, while overlapping upbeat nystagmus with torsional right-beating components appeared on the right. Primary clinical findings were consistent with a left horizontal semicircular canalith jam, inducing a persistent utriculofugal cupular displacement, combined with a typical right-sided PSC-canalolithiasis. Once canalith jam crumbled, resulting in a non-ampullary arm canalolithiasis of the horizontal semicircular canal, both involved canals were freed by debris with appropriate repositioning procedures.

Recently WHO has declared novel coronavirus disease 2019 (COVID-19) outbreak a pandemic. Acute respiratory syndrome seems to be the most common manifestation of COVID-19. Besides pneumonia, it has been demonstrated that SARS-CoV-2 infection affects multiple organs, including brain tissues, causing different neurological manifestations, especially acute cerebrovascular disease (ischemic and hemorrhagic stroke), impaired consciousness and skeletal muscle injury. To our knowledge, among neurological disorders associated with SARS-CoV2 infection, no Posterior Reversible Encephalopathy Syndrome (PRES) has been described yet. Herein, we report a case of a 64-year old woman with COVID19 infection who developed a PRES, and we suggest that it could be explained by the disruption of the blood brain barrier induced by the cerebrovascular endothelial dysfunction caused by SARS-CoV-2.

Background Homelessness and unstable housing (HUH) negatively impact care outcomes for people living with HIV (PLWH). To inform the design of a clinic program for PLWH experiencing HUH, we quantified patient preferences and trade-offs across multiple HIV-service domains using a discrete choice experiment (DCE). Methods We sequentially sampled PLWH experiencing HUH presenting at an urban HIV clinic with ≥1 missed primary care visit and viremia in the last year to conduct a DCE. Participants chose between 2 hypothetical clinics varying across 5 service attributes: care team "get to know me as a person" versus not; receiving $10, $15, or $20 gift cards for clinic visits; drop-in versus scheduled visits; direct phone communication to care team versus front-desk staff; and staying 2 versus 20 blocks from the clinic. We estimated attribute relative utility (ie, preference) using mixed-effects logistic regression and calculated the monetary trade-off of preferred options. Results Among 65 individuals interviewed, 61% were >40 years old, 45% White, 77% men, 25% heterosexual, 56% lived outdoors/emergency housing, and 44% in temporary housing. Strongest preferences were for patient-centered care team [β = 3.80; 95% confidence interval (CI): 2.57 to 5.02] and drop-in clinic appointments (β = 1.33; 95% CI: 0.85 to 1.80), with a willingness to trade $32.79 (95% CI: 14.75 to 50.81) and $11.45 (95% CI: 2.95 to 19.95) in gift cards/visit, respectively. Conclusions In this DCE, PLWH experiencing HUH were willing to trade significant financial gain to have a personal relationship with and drop-in access to their care team rather than more resource-intensive services. These findings informed Ward 86's "POP-UP" program for PLWH-HUH and can inform "ending the HIV epidemic" efforts.

Purpose of Review Singular interventions targeting vulnerable populations of people living with HIV (PLWH) are necessary for reducing new infections and optimizing individual-level outcomes, but extant literature for PLWH who experience homelessness and unstable housing (HUH) has not been compiled. To inform implementation of clinic-based programs that improve care outcomes in this population, we present a synthetic review of key studies examining clinic-based interventions, specifically case management, patient navigation, financial incentives, and the use of mobile technology. Recent Findings Results from unimodal interventions are mixed or descriptive, are limited by inability to address related multimodal barriers to care, and do not address major challenges to implementation. Summary Multi-component interventions are needed, but gaps in our knowledge base may limit widespread uptake of such interventions before further data are compiled. Future research evaluating interventions for PLWH experiencing HUH should include implementation outcomes in order to facilitate adaptation across diverse clinical settings.

Objective: Residual dizziness is a disorder of unknown pathophysiology, which may occur after repositioning procedures for benign paroxysmal positional vertigo. This study evaluates the relationship between regular daily physical activity and the development of residual dizziness after treatment for benign paroxysmal positional vertigo. Study Design: Prospective observational cohort study. Setting: Academic university hospital. Methods: Seventy-one patients admitted with benign paroxysmal positional vertigo involving the posterior semicircular canal were managed with Epley’s procedure. Three days after successful treatment, the patients underwent a telephone interview to investigate vertigo relapse. If the patients no longer complained of vertigo, they were asked about symptoms consistent with residual dizziness. Subsequently, they were asked about the recovery of physical activities they regularly performed prior to the onset of vertigo. Results: Sixty-nine patients (age: 57.79 ± 15.05) were enrolled: five (7.24%) reported vertigo relapse whereas twenty-one of sixty-four non-relapsed patients (32.81%) reported residual dizziness. A significant difference in the incidence of residual dizziness was observed considering the patients’ age (p = 0.0003). Of the non-relapsed patients, 46 (71.88%) recovered their regular dynamic daily activities after treatment and 9 (19.57%) reported residual dizziness, while 12 of the 18 patients (66.67%) who did not resume daily activity reported residual symptoms (p = 0.0003). A logistic regression analysis showed a significant association between daily activity resumption and lack of residual dizziness (OR: 14.01, 95% CI limits 3.14–62.47; p = 0.001). Conclusions: Regardless of age, the resumption of regular daily physical activities is associated with a lack of residual dizziness.

Posterior reversible encephalopathy cases are increasingly being reported in patients affected by COVID-19, but the largest series so far only includes 4 patients. We present a series of 6 patients diagnosed with PRES during COVID-19 hospitalized in 5 Centers in Lombardia, Italy. 5 out of the 6 patients required intensive care assistence and seizures developed at weaning from assisted ventilation. 3 out of 6 patients underwent cerebrospinal fluid analysis which was normal in all cases, with negative PCR for Sars-CoV-2 genome search. PRES occurrence may be less rare than supposed in COVID-19 patients and a high suspicion index is warranted for prompt diagnosis and treatment., Highlights • Posterior reversible encephalopathy syndrome is increasingly being reported in COVID-19 patients. • Weaning from assisted ventilation may be a critical moment in seizure development. • No evidence of viral genome in the cerebrospinal fluid in this cohort

Background: Several studies focused on the possible role of vitamin D (vitD) in pain chronicization.. The aim of this study was to assess the potential implications of VitD deficit on headache characteristics and extracranial pain extension.Methods: Eighty consecutive patients with primary headache underwent neurological examination, laboratory exams including serum calcifediol 25(OH)D and headache features assessment along with three questionnaires investigating depression, anxiety and allodynia. Results: The 82.6% of the population had migraine (48% episodic and 52% chronic form). The 45% of patients had extracranial pain and 47% suffered from allodynia. In the 45% of patients had a VitD deficit since the serum 25(OH)D levels fell below the cut-off level of 20 ng/ml. The occurrence of VitD deficit was significantly higher (p=0.009) in patients suffering from chronic migraine (CM)- medication overuse migraine (MOH) (64.7%) than in episodic migraine (EM) or tension type headache (TTH). The occurrence of subjects with extracranial pain and allodynia was higher, as expected, in the CM-MOH than in the EM and in the TTH groups but was not related to the co-occurrence of vit-D deficiency (Fischer’s exact test p=0.11 and p=0.32 respectively).Conclusions: Our findings show that 25(OH)D deficit is related to chronic pain suggesting that vitD probably has anti-inflammatory and tolerogenic properties, rather than a direct antinociceptive effect, and reinforce the idea of a neuroinflammatory mechanisms underpinning migraine chronicization.

During the COVID-19 outbreak, the Neurology and Stroke Unit (SU) of the hospital of Varese had to serve as a cerebrovascular hub, meaning that the referral area for the unit doubled. The number of beds in the SU was increased from 4 to 8. We took advantage of the temporary suspension of the out-patient clinic and reshaped our activity to guarantee the 24/7 availability of recombinant tissue Plasminogen Activator (rtPA) intravenous therapy (IVT) in the SU, and to ensure we were able to admit patients to the SU as soon as they completed endovascular treatment (EVT). In 42 days, 46 stroke patients were admitted to our hospital, and 34.7% of them underwent IVT and/or EVT, which means that we treated 0.38 patients per day; in the baseline period from 2016 to 2018, these same figures had been 23.5% and 0.23, respectively. The mean values of the door-to-first CT/MRI and the door-to-groin puncture, but not of the onset-to-door and the door-to-needle periods were slightly but significantly longer than those observed in the baseline period in 276 patients. On an individual basis, only one patient exceeded the door-to-groin puncture time limit computed from the baseline period by about 10 min. None of the patients had a major complication following the procedures. None of the patients was or became SARS-CoV2 positive. In conclusion, we were able to manage the new hub-and-spoke system safely and without significant delays. The reshaping of the SU was made possible by the significant reduction of out-patient activity. The consequences of this reduction are still unknown but eventually, this emergency will suggest ways to reconsider the management and the allocation of health system resources.

Objective Homelessness is the greatest risk factor for HIV viremia in San Francisco. Innovative care models for people with HIV (PWH) with homelessness or unstable housing (HUH) are needed to address this inequity. We developed a novel low-barrier clinic-based program for PWH-HUH in an urban safety-net clinic ('POP-UP') and report outcomes on care engagement and viral suppression. Design A prospective cohort study. Setting San Francisco General Hospital HIV Clinic (Ward 86). Participants We enrolled PWH who are HUH, viraemic and for whom usual care is not working (at least one missed primary care appointment and at least two drop-in visits at Ward 86 in the last year). Intervention POP-UP provides drop-in comprehensive primary care, housing assistance and case management, financial incentives and patient navigation with frequent contact. Main outcome measures We describe uptake of eligible patients into POP-UP, and cumulative incidence of antiretroviral therapy (ART) initiation, return to care and virologic suppression 6 months post-enrolment, estimated via Kaplan--Meier. Results Out of 192 referred patients, 152 were eligible, and 75 enrolled. All 75 were off ART and viraemic; 100% had a substance use disorder; and 77% had a mental health diagnosis. Over three-quarters restarted ART within 7 days of enrolment, and 91% returned for follow-up within 90 days. The cumulative incidence of viral suppression at 6 months was 55% (95% confidence interval 43-68). Conclusion A novel care model for PWH-HUH demonstrates early success in engaging viraemic patients in care and improving viral suppression. Low-barrier, high-contact primary care programmes offering comprehensive services and incentives may improve outcomes for this vulnerable population.

Gonorrhea and chlamydia (GC/CT) testing falls below recommended rates for people living with HIV (PLWH) in routine care. Despite evidence that homelessness and unstable housing (HUH) negatively impacts clinical outcomes for PLWH, little is known about GC/CT screening for HUH-PLWH in routine care.Using an observational cohort of PLWH establishing care at a large publicly funded HIV clinic in San Francisco between February 2013 and December 2014 and with at least 1 primary care visit (PCV) before February 2016, we assessed GC/CT testing for HUH (staying outdoors, in shelters, in vehicles, or in places not made for habitation in the last year) compared with stably housed patients. We calculated (1) the odds of having GC/CT screening at a PCV using logistic regression with random effects to handle intrasubject correlations and (2) the percent of time enrolled in clinical care in which patients had any GC/CT testing ("time in coverage") based on 180-day periods and using linear regression modeling.Of 323 patients, mean age was 43 years, 92% were male, 52% were non-Latino white, and 46% were HUH. Homeless and unstably housed PLWH had 0.66 odds of GC/CT screening at a PCV than did stably housed patients (95% confidence interval, 0.44-0.99; P = 0.043). Time in coverage showed no difference by housing status (regression coefficient, -0.93; 95% confidence interval, -8.02 to 6.16; P = 0.80).Homeless and unstably housed PLWH had 34% lower odds of GC/CT screening at a PCV, demonstrating a disparity in routine care provision, but similar time in coverage. More research is needed to effectively increase GC/CT screening among HUH-PLWH.

Coronavirus disease-2019 (COVID-19) threatens to further worsen HIV outcomes among people experiencing homelessness. We conducted an interrupted time-series analysis of care engagement and viral suppression among unhoused individuals in the 'POP-UP' low-barrier, high-intensity HIV primary care program during COVID-19. Among 85 patients, care engagement and viral suppression did not decrease in the 5 months following implementation of San Francisco's 'shelter-in-place' ordinance. Low-barrier, in-person HIV care for homeless individuals may be important for maintaining HIV outcomes during COVID-19.

Western diets that are high in saturated fat and sugar disrupt circadian rhythms, induce weight gain, and lead to metabolic diseases including obesity. However, the mechanistic link between altered circadian rhythms and energy homeostasis remains poorly understood. In C57BL/6J mice, consuming a Western diet for 16 weeks significantly reduced food intake (at zeitgeber 12–16), in association with decreases in hypothalamic expression of the orexigenic neuropeptides, neuropeptide Y (Npy) and agouti-related peptide (AgRP). To examine the acute effects of the most prevalent saturated fatty acid in a Western diet, palmitate, and the role of the core clock gene, Bmal1, in the regulation of hypothalamic feeding neuropeptides, we used heterogeneous and clonal BMAL1 knockout (KO) immortalized hypothalamic cell lines, expressing specific neuropeptides, derived from male (M) and female (F) mice. Both mHypoA-BMAL1-KO/F and mHypoA-BMAL1-KO/M cells demonstrated a loss of circadian rhythmicity in expression of the clock gene, Per2, as compared to wild-type (control) cultures. Loss of BMAL1 also altered the time-dependent expression of Npy and proopiomelanocortin, and disrupted AgRP rhythmicity. Furthermore, palmitate increased BMAL1 binding to the Npy promotor region, and palmitate treatment (50 μM for 24 h) stimulated Npy expression in a BMAL1-dependent manner in both heterogeneous and clonal NPY-expressing female-derived cell models. The results of this study demonstrate that circadian expression of Bmal1 serves as a mechanistic link between Western diet- and palmitate-induced disruptions of the normal rhythmic patterns in hypothalamic feeding-related neuropeptides.

Saliva is an essential body fluid. It is important in maintaining oral health, taste acuity, mastication, deglutition, digestion, regulation of oral flora, oral cleansing, voice acuity, and speech articulation. In the elderly, the glandular parenchyma undergoes involution of the cellular component, and this leads to a reduction in the production of saliva. Qualitative and quantitative alterations of this biological fluid can cause patient discomfort and quality of life decline. This often translates into xerostomia, whose real meaning is mouth dryness. We will discuss here causes of xerostomia in the elderly, such as drugs, head and neck radiotherapy, and autoimmune diseases.

Background:The diagnosis of benign paroxysmal positional vertigo (BPPV) involving the lateral semicircular canal (LSC) is traditionally entrusted to the supine head roll test, also known as supine head yaw test (SHYT), which usually allows identification of the pathologic side and BPPV form (geotropic vs. apogeotropic). Nevertheless, SHYT may not always allow easy detection of the affected canal, resulting in similar responses on both sides and intense autonomic symptoms in patients with recent onset of vertigo. The newly introduced upright head roll test (UHRT) represents a diagnostic maneuver for LSC-BPPV, supplementing the already-known head pitch test (HPT) in the sitting position. The combination of these two tests should enable clinicians to determine the precise location of debris within LSC, avoiding disturbing symptoms related to supine positionings. Therefore, we proposed the upright BPPV protocol (UBP), a test battery exclusively performed in the upright position, including the evaluation of pseudo-spontaneous nystagmus (PSN), HPT and UHRT. The purpose of this multicenter study is to determine the feasibility of UBP in the diagnosis of LSC-BPPV.Methods:We retrospectively reviewed the clinical data of 134 consecutive patients diagnosed with LSC-BPPV. All of them received both UBP and the complete diagnostic protocol (CDP), including the evaluation of PSN and data resulting from HPT, UHRT, seated-supine positioning test (SSPT), and SHYT.Results:A correct diagnosis for LSC-BPPV was achieved in 95.5% of cases using exclusively the UBP, with a highly significant concordance with the CDP (p< 0.000, Cohen's kappa = 0.94), regardless of the time elapsed from symptom onset to diagnosis. The concordance between UBP and CDP was not impaired even when cases in which HPT and/or UHRT provided incomplete results were included (p< 0.000). Correct diagnosis using the supine diagnostic protocol (SDP, including SSPT + SHYT) or the sole SHYT was achieved in 85.1% of cases, with similar statistical concordance (p< 0.000) and weaker strength of relationship (Cohen's kappa = 0.80).Conclusion:UBP allows correct diagnosis in LSC-BPPV from the sitting position in most cases, sparing the patient supine positionings and related symptoms. UBP could also allow clinicians to proceed directly with repositioning maneuvers from the upright position.

Background: Pain is a common and heterogeneous complication of multiple sclerosis (MS). In this multicenter, cross sectional study, we aimed at investigating the prevalence of pain in MS using highly specific criteria for distinguishing the different types of pain. Materials and methods: After a structured interview, in patients with pain, clinical examination and DN4 questionnaire were used for distinguishing neuropathic and nociceptive pain. In subjects with neuropathic pain, the Neuropathic Pain Symptom Inventory was used for differentiating neuropathic pain symptoms. Results: We enrolled 1249 participants (832 F, 417 M, mean age 33.9 years, mean disease duration 8 years, mean EDSS 3.2); based on clinical evaluation and DN4 score 429 patients (34.34%) were classified with pain (470 pain syndromes): 286 nociceptive pain syndromes and 184 neuropathic pain syndromes. Multivariate analysis showed that pain was associated with age, gender and disease severity and that neuropathic pain was distinctly associated with EDSS. Conclusions: Our study, providing definite information on the prevalence, characteristics and variables associated with neuropathic pain due to MS, shows that a more severe disease course is associated with a higher risk of neuropathic pain. Our findings might, therefore, provide a basis for improving the clinical management of this common MS complication.

While poverty is an established barrier to achieving success at each step of the HIV care continuum, less is known about specific aspects of poverty and how they overlap with behavior in exceptionally low-income individuals who live in well-resourced areas. We considered unsuppressed viral load over three years among women living with HIV in San Francisco who used homeless shelters, low-income hotels and free meal programs. One-hundred twenty study participants were followed; 60% had ≥1 unsuppressed viral load and 19% were unsuppressed at every visit. Across six-month intervals, the odds of unsuppressed viral load were 11% higher for every 10 nights spent sleeping on the street (Adjusted Odds Ratio [AOR] =1.11, 95% CI:1.02-1.20); 16% higher for every 10 nights spent sleeping in a shelter (AOR/10 nights= 1.16, 95% CI: 1.06-1.27); 4% higher for every 10 nights spent sleeping in a single-room occupancy hotel (AOR/10 nights= 1.04, 95% CI: 1.02-1.07); and almost four-fold higher among women who experienced any recent incarceration (AOR=3.56, 95% CI: 1.84-6.86). Violence and recent use of outpatient health care did not significantly predict viral suppression in adjusted analysis. While strategies to promote retention in care are important for vulnerable persons living with HIV, they are insufficient to ensure sustained viral suppression in low-income women experiencing homelessness and incarceration. Results presented here in combination with prior research linking incarceration to homelessness among women indicate that tailored interventions, which not only consider but prioritize affordable housing, are critical to achieving sustained viral suppression in low-income women living with HIV.

BACKGROUND: Staphylococcus aureus is a leading cause of bacteremia, yet there remains a significant knowledge gap in the identification of relevant biomarkers that predict clinical outcomes. Heterogeneity in the host response to invasive S. aureus infection suggests that specific biomarker signatures could be utilized to differentiate patients prone to severe disease, thereby facilitating earlier implementation of more aggressive therapies. METHODS: To further elucidate the inflammatory correlates of poor clinical outcomes in patients with S. aureus bacteremia, we evaluated the association between a panel of blood proteins at initial presentation of bacteremia and disease severity outcomes using 2 cohorts of patients with S. aureus bacteremia (n = 32 and n = 124). RESULTS: We identified 13 candidate proteins that were correlated with mortality and persistent bacteremia. Prognostic modeling identified interleukin (IL)-8 and CCL2 as the strongest individual predictors of mortality, with the combination of these biomarkers classifying fatal outcome with 89% sensitivity and 77% specificity (P < .0001). Baseline IL-17A levels were elevated in patients with persistent bacteremia (P < .0001), endovascular (P = .026) and metastatic tissue infections (P = .012). CONCLUSIONS: These results demonstrate the potential utility of selected biomarkers to distinguish patients with the highest risk for treatment failure and bacteremia-related complications, providing a valuable tool for clinicians in the management of S. aureus bacteremia. Additionally, these biomarkers could identify patients with the greatest potential to benefit from novel therapies in clinical trials.

Circadian rhythms drive the timing of daily physiological functions, including food intake. These cellular rhythms depend on the intricate regulation of core clock genes, such as BMAL1. Disruptions of the molecular clock in rodents have been shown to induce obesity and features of the metabolic syndrome, as well as altering diurnal food intake patterns. In vitro studies using palmitate, a saturated fatty acid comprising a large portion of high-fat diets, demonstrate alterations in hypothalamic BMAL1 and feeding-related neuropeptide expression. We hypothesized that the high-fat, high-sugar (Western) diet alters circadian food intake rhythms by altering hypothalamic feeding-related neuropeptide expression in a BMAL1-dependent manner. C57BL/6-J mice were fed either rodent chow (RC; control) or Western diet (WD) for 16 weeks. Male and female WD mice gained more weight compared to controls, and consumed a larger proportion of their food during the inactive (light) period. Hypothalamic mRNA expression patterns of neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC) were markedly altered by WD feeding. Compared to RC controls, WD mice showed a blunted mRNA expression of AgRP and NPY, accompanied by an altered hypothalamic expression of the clock genes BMAL1 and Per2. To identify the cellular mechanism by which the WD affects the central control of food intake, hypothalamic cell lines were derived from adult BMAL1-wildtype (WT) and knockout (KO) C57BL/6-J mice. Hypothalamic primary cultures were immortalized with SV40 T-antigen and characterized to demonstrate a robust rhythmic cycling of clock gene expression, in addition to the expression of several neuropeptides. Importantly, BMAL1-WT neurons exhibited a 24-hour period in Per2 clock gene mRNA expression, while the BMAL1-KO cell line lacked rhythmic expression of Per2, confirming the cell line as a hypothalamic model of circadian disruption. Additionally, the expression patterns of NPY, AgRP, and POMC were altered with BMAL1 knockout. Treatment with palmitate increased BMAL1, Per2, and POMC expression at 9 or 21 hours, corresponding to the peak and trough of clock and neuropeptide mRNA expression. Taken together, these results suggest a role for the circadian clock in regulating hypothalamic neuropeptide expression and, thereby, central control of food intake. Sources of research support: MNC has received graduate awards from the Banting and Best Diabetes Centre and the Ontario Graduate Scholarship; studies were supported by CIHR and NSERC operating grants. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Summary Background The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Background Staphylococcus aureus (SA) bacteremia often requires a long treatment duration with antibiotics to prevent relapse due to the ability of SA to establish reservoirs of infection in sites such as heart and bone. These metastatic sites of infection cannot be serially sampled to monitor the clearance of SA infection. This study aimed to establish a link between persistence of circulating SA deoxyribonucleic acid (SA-DNA) and tissue reservoirs in patients with SA bacteremia. Methods A highly sensitive quantitative polymerase chain reaction was used to measure whole blood SA-DNA and plasma-derived SA cell-free DNA (SA-cfDNA) in a set of longitudinal samples from 73 patients with confirmed SA bacteremia and correlated with clinical features. Results Blood SA-DNA was detected for longer than the duration of positive blood cultures. Longer duration of circulating bacterial DNA was observed in complicated SA bacteremia infections, such as endocarditis and osteoarticular infections, compared with uncomplicated bloodstream infections. In contrast, traditional blood cultures demonstrated similar time to clearance regardless of foci of infection. Plasma-derived SA-cfDNA showed concordance with blood SA-DNA levels. Baseline levels of SA-DNA were higher in patients presenting with greater clinical severity and complicated bacteremia. Conclusions Prolonged levels of circulating SA-DNA in patients with complicated tissue reservoirs after clearance of blood cultures observed in this single-center study should be validated in additional cohorts to assess the potential utility for monitoring clearance of infection in patients with SA bacteremia.

Background People living with HIV (PLWH) who experience homelessness and unstable housing (HUH) often have fragmented health care. Research that incorporates granular assessments of housing status and primary care visit adherence to understand patterns of acute care utilization can help pinpoint areas for intervention. Methods We collected self-reported living situation, categorized as stable (rent/own, hotel/single room occupancy), unstable (treatment/transitional program, staying with friends), or homeless (homeless shelter, outdoors/in vehicle) at an urban safety-net HIV clinic between February and August 2017 and abstracted demographic and clinical information from the medical record. Regression models evaluated the association of housing status on the frequency of acute care visits—urgent care (UC) visits, emergency department (ED) visits, and hospitalizations—and whether suboptimal primary care visit adherence ( Results Among 1198 patients, 25% experienced HUH. In adjusted models, unstable housing resulted in a statistically significant increase in the incidence rate ratio for UC visits (incidence rate ratio [IRR], 1.35; 95% confidence interval [CI], 1.10 to 1.66; P < .001), ED visits (IRR, 2.12; 95% CI, 1.44 to 3.13; P < .001), and hospitalizations (IRR, 1.75; 95% CI, 1.10 to 2.77; P = 0.018). Homelessness led to even greater increases in UC visits (IRR, 1.75; 95% CI, 1.29 to 2.39; P < .001), ED visits (IRR, 4.18; 95% CI, 2.77 to 6.30; P < .001), and hospitalizations (IRR, 3.18; 95% CI, 2.03 to 4.97; P < .001). Suboptimal visit adherence differentially impacted UC and ED visits by housing status, suggesting interaction. Conclusions Increased acute care visit frequency among HUH-PLWH suggests that interventions at these visits may create opportunities to improve care.

The links between obesity, inflammation and insulin resistance, which are all key characteristics of type 2 diabetes mellitus, are yet to be delineated in the brain. One of the key neuroinflammatory proteins detected in the hypothalamus with over-nutrition is tumour necrosis factor (TNF)α. Using immortalised embryonic rat and mouse hypothalamic cell lines (rHypoE-7 and mHypoE-46) that express orexigenic neuropeptide Y and agouti-related peptide, we investigated changes in insulin signalling and inflammatory gene marker mRNA expression after TNFα exposure. A quantitative polymerase chain reaction array of 84 inflammatory markers (cytokines, chemokines and receptors) demonstrated an increase in the expression of multiple genes encoding inflammatory markers upon exposure to 100 ng mL-1 TNFα for 4 hours. Furthermore, neurones pre-exposed to TNFα (50 ng mL-1 ) for 6 or 16 hours exhibited a significant reduction in phosphorylated Akt compared to control after insulin treatment, indicating the attenuation of insulin signalling. mRNA expression of insulin signalling-related genes was also decreased with exposure to TNFα. TNFα significantly increased mRNA expression of IκBα, Tnfrsf1a and IL6 at 4 and 24 hours, activating a pro-inflammatory state. An inhibitor study using an inhibitor of nuclear factor kappa B kinase subunit β (IKK-β) inhibitor, PS1145, demonstrated that TNFα-induced neuroinflammatory marker expression occurs through the IKK-β/nuclear factor-kappa B pathway, whereas oleate, a monounsaturated fatty acid, had no effect on inflammatory markers. To test the efficacy of anti-inflammatory treatment to reverse insulin resistance, neurones were treated with TNFα and PS1145, which did not significantly restore the TNFα-induced changes in cellular insulin sensitivity, indicating that an alternative pathway may be involved. In conclusion, exposure to the inflammatory cytokine TNFα causes cellular insulin resistance and inflammation marker expression in the rHypoE-7 and mHypoE-46 neurones, consistent with effects seen with TNFα in peripheral tissues. It also mimics insulin- and palmitate-induced insulin resistance in hypothalamic neurones. The present study provides further evidence that altered central energy metabolism may be caused by obesity-induced cytokine expression.

The brain, specifically the hypothalamus, controls whole body energy and glucose homeostasis through neurons that synthesize specific neuropeptides, whereas hypothalamic dysfunction is linked directly to insulin resistance, obesity, and type 2 diabetes mellitus. Nutrient excess, through overconsumption of a Western or high-fat diet, exposes the hypothalamus to high levels of free fatty acids, which induces neuroinflammation, endoplasmic reticulum stress, and dysregulation of neuropeptide synthesis. Furthermore, exposure to a high-fat diet also disrupts normal circadian rhythms, and conversely, clock gene knockout models have symptoms of metabolic disorders. While whole brain/animal studies have provided phenotypic end points and important clues to the genes involved, there are still major gaps in our understanding of the intracellular pathways and neuron-specific components that ultimately control circadian rhythms and energy homeostasis. Because of its complexity and heterogeneous nature, containing a diverse mix cell types, it is difficult to dissect the critical hypothalamic components involved in these processes. Of significance, we have the capacity to study these individual components using an extensive collection of both embryonic- and adult-derived, immortalized hypothalamic neuronal cell lines from rodents. These defined neuronal cell lines have been used to examine the impact of nutrient excess, such as palmitate, on circadian rhythms and neuroendocrine signaling pathways, as well as changes in vital neuropeptides, leading to the development of neuronal inflammation; the role of proinflammatory molecules in this process; and ultimately, restoration of normal signaling, clock gene expression, and neuropeptide synthesis in disrupted states by beneficial anti-inflammatory compounds in defined hypothalamic neurons.

Housing instability negatively impacts outcomes in people living with human immunodeficiency virus (PLHIV), yet the effect of diverse living arrangements has not previously been evaluated. Using 6 dwelling types to measure housing status, we found a strong inverse association between housing instability and viral suppression across a spectrum of unstable housing arrangements.

© 2018 Jason Coquim et al. This investigation assessed the biomechanical performance of the metal plate and bone strut technique for fixing recalcitrant nonunions of femur midshaft segmental defects, which has not been systematically done before. A finite element (FE) model was developed and then validated by experiments with the femur in 15 deg of adduction at a subclinical hip force of 1 kN. Then, FE analysis was done with the femur in 15 deg of adduction at a hip force of 3 kN representing about 4 x body weight for a 75 kg person to examine clinically relevant cases, such as an intact femur plus 8 different combinations of a lateral metal plate of fixed length, a medial bone strut of varying length, and varying numbers and locations of screws to secure the plate and strut around a midshaft defect. Using the traditional “high stiffness” femur-implant construct criterion, the repair technique using both a lateral plate and a medial strut fixed with the maximum possible number of screws would be the most desirable since it had the highest stiffness (1948 N/mm); moreover, this produced a peak femur cortical Von Mises stress (92 MPa) which was below the ultimate tensile strength of cortical bone. Conversely, using the more modern “low stiffness” femur-implant construct criterion, the repair technique using only a lateral plate but no medial strut provided the lowest stiffness (606 N/mm), which could potentially permit more in-line interfragmentary motion (i.e., perpendicular to the fracture gap, but in the direction of the femur shaft long axis) to enhance callus formation for secondary-type fracture healing; however, this also generated a peak femur cortical Von Mises stress (171 MPa) which was above the ultimate tensile strength of cortical bone.

Background: Lower thermal and discomfort thresholds may predispose multiple sclerosis (MS) patients to chronic pain, but a possible effect of fibromyalgia (FM) comorbidity has never been investigated. Aims were to investigate the thermal and discomfort thresholds in the evaluation of pain intensity between MS patients with FM (PFM+) and MS patients with pain not associated to FM (PFM−). Methods: One hundred thirty three MS patients were investigated for chronic pain. FM was assessed according to the 1990 ACR diagnostic criteria. An algometer was used to measure the thresholds in the patients and 60 matched healthy subjects. Results: Chronic pain was present in 88 (66.2%) patients; 12 (13.6%) had neuropathic pain, 22 (17.3%) were PFM+ and 65 (48.9%) PFM−. PFM+ were predominantly female (p = 0.03) and had a greater EDSS (p = 0.01) than NoP; no other significant differences emerged than PFM−. The thresholds were lower in MS patients than controls (p < 0.01), mainly in the PFM+. FM severity influenced the thermal threshold (p < 0.001), while the female gender influenced the discomfort threshold (p < 0.001). Conclusion: Thermal and discomfort thresholds were lower in patients than controls and were the lowest in PFM+. Their more severely impaired thermal threshold supports a neurophysiological basis of such association.

Background Depression occurs in about 50% of patients with multiple sclerosis. The aims of this study was to investigate the prevalence of depressive symptoms in a multicenter MS population using the Beck Depression Inventory II (BDI II) and to identify possible correlations between the BDI II score and demographic and clinical variables. Methods Data were collected in a multi-center, cross-sectional study over a period of six months in six MS centers in Italy using BDI II. Results 1,011 MS patients participated in the study. 676 subjects were female, with a mean age of 34 years (SD 10.8), mean EDSS of 3.3 (0–8.5) and mean disease duration of 10.3 years (range 1–50 years). 668 (%) subjects scored lower than 14 on the BDI II and 343 (33.9%) scored greater than 14 (14 cut-off score). For patients with BDI>14 multivariate analysis showed a significant difference between EDSS and disease course. BDI II scores for subjects with secondary progressive (SP) MS were significantly different from primary progressive (PP) patients (p < 0.001) but similar to relapsing-remitting (RR) patients. Considering subjects with moderate to severe depressive symptoms (BDI II score from 20–63), in relation to disease course, 11.7% (83/710) had RR MS, 40.7% (96/236) SP and 13.6% (6/44) PP. Conclusions Using the BDI II, 30% of the current sample had depressive symptoms. BDI II score correlates with disability and disease course, particularly in subjects with SP MS. The BDI II scale can be a useful tool in clinical practice to screen depressive symptoms in people with MS.

Background: Robotic training is commonly used to assist walking training in patients affected by multiple sclerosis (MS) with non-conclusive results. Objective: To compare the effect of robot-assisted gait training (RAGT) with that of conventional walking training (CWT) on gait competencies, global ability, fatigue and spasticity in a group of severely affected patients with MS. Methods: A pilot, single-blind randomized controlled trial was conducted in 43 severe (Expanded Disability Status Scale (EDSS) score of 6–7.5) and non-autonomous ambulant in-patients with MS. Experimental group performed 12 sessions of RAGT, whereas control group performed the same amount of CWT. Primary outcome measures were gait ability assessed by 2 minutes walking test and Functional Ambulatory Category; secondary outcomes were global ability (modified Barthel Index), global mobility (Rivermead Mobility Index), severity of disease (EDSS) and subjectively perceived fatigue (Fatigue Severity Scale). Results: The number of subjects who achieved a clinical significant improvement was significantly higher in RAGT than in CWT ( p Conclusions: RAGT improved the walking competencies in non-autonomous ambulant patients with MS, with benefits in terms of perceived fatigue.

Background Chronic pain is common in persons with multiple sclerosis (MS), but the co-morbidity of fibromyalgia (FM) has yet to be investigated in MS. Objectives of the study were to evaluate, among the various types of chronic pain, the frequency of FM in MS and its impact on MS patients' health-related quality of life (HRQoL). Material and methods 133 MS patients were investigated for the presence and characterization of chronic pain within 1 month of assessment. A rheumatologist assessed the presence FM according to the 1990 ACR diagnostic criteria. Depression, fatigue, and HRQoL were also assessed by means of specific scales. Results Chronic pain was present in 66.2% of patients (musculoskeletal in 86.3%; neuropathic in 13.7%; absent in 33.8% [called NoP]). Pain was diagnosed with FM (PFM+) in 17.3% of our MS patients, while 48.9% of them had chronic pain not FM type (PFM-); the prevalence of neuropathic pain in these 2 sub-groups was the same. PFM+ patients were prevalently females and had a higher EDSS than NoP. The PFM+ patients had a more pronounced depression than in the NoP group, and scored the worst in both physical and mental QoL. Conclusions In our sample of MS patients we found a high prevalence of chronic pain, with those patients displaying a higher disability and a more severe depression. Moreover, FM frequency, significantly higher than that observed in the general population, was detected among the MS patients with chronic pain. FM occurrence was associated with a stronger impact on patients' QoL.

Background: We reported that 6-month therapy with intravenous immunoglobulin (IVIg) was more frequently effective or tolerated than intravenous methylprednisolone (IVMP) in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We now retrospectively compared the proportion of patients who eventually worsened after discontinuing therapy and the median time to clinical worsening. Methods: By March 2013, data were available from 41 of the 45 patients completing the trial with a median follow-up after therapy discontinuation of 42 months (range 1-60). Three patients withdrew during the original study and one failed to respond to either of the therapies. No patient received a diagnosis alternative to CIDP during the follow-up. Results: Twenty-eight of the 32 patients treated with IVIg (as primary or secondary therapy after failing to respond to IVMP) improved after therapy (87.5%) as compared with 13 of the 24 patients treated with IVMP as primary or secondary therapy (54.2%). After a median follow-up of 42 months (range 1-57), 24 out of 28 patients responsive to IVIg (85.7%) worsened after therapy discontinuation. The same occurred in 10 out of 13 patients (76.9%) responsive to IVMP (p=0.659) after a median follow-up of 43 months (range 7-60). Worsening occurred 1-24 months (median 4.5) after IVIg discontinuation and 1-31 months (median 14) after IVMP discontinuation (p=0.0126). Conclusions: A similarly high proportion of patients treated with IVIg or IVMP eventually relapse after therapy discontinuation but the median time to relapse was significantly longer after IVMP than IVIg. This difference may help to balance the more frequent response to IVIg than to IVMP in patients with CIDP.

Staphylococcus aureus bacteremia (SAB) is a tremendous health burden. Previous studies examining the association of vancomycin MIC and outcomes in patients with SAB have been inconclusive. This study evaluated the association between vancomycin MICs and 30- or 90-day mortality in individuals with SAB. This was a prospective cohort study of adults presenting from 2008 to 2013 with a first episode of SAB. Subjects were identified by an infection surveillance system. The main predictor was vancomycin MIC by MicroScan. The primary outcomes were death at 30 and 90 days, and secondary outcomes included recurrence, readmission, or a composite of death, recurrence, and readmission at 30 and 90 days. Covariates included methicillin susceptibility, demographics, illness severity, comorbidities, infectious source, and antibiotic use. Cox proportional-hazards models with propensity score adjustment were used to estimate 30- and 90-day outcomes. Of 429 unique first episodes of SAB, 11 were excluded, leaving 418 individuals for analysis. Eighty-three (19.9%) participants had a vancomycin MIC of 2 μg/ml. In the propensity-adjusted Cox model, a vancomycin MIC of 2 μg/ml compared to P = 0.70] and 0.94 [95% CI, 0.55, 1.58] [ P = 0.80], respectively) or 90 days (HRs of 0.91 [95% CI, 0.49, 1.69] [ P = 0.77] and 0.69 [95% CI, 0.46, 1.04] [ P = 0.08], respectively) after SAB diagnosis. In a prospective cohort of patients with SAB, vancomycin MIC was not associated with 30- or 90-day mortality or a composite of mortality, disease recurrence, or hospital readmission.

BackgroundThymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone.MethodsWe compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period.ResultsA total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P

Fever of unknown origin (FUO) can be an unusual first clinical manifestation of pheochromocytoma. Pheochromocytomas are tumors that may produce a variety of substances in addition to catecholamines. To date, several cases of IL-6-producing pheochromocytomas have been reported. This report describes a 45-year-old woman with pheochromocytoma who was admitted with FUO, normal blood pressure levels, microcytic and hypochromic anemia, thrombocytosis, hyperfibrinogenemia, hypoalbuminemia, and normal levels of urine and plasma metanephrines. After adrenalectomy, fever and all inflammatory findings disappeared.

To evaluate the efficacy and the safety of repeated botulinum toxin type A (BT-A) injections in patients with severe acquired brain injury (ABI) and to gain a better knowledge of possible clinical or demographic characteristics associated with a better rehabilitation outcome.Prospective study with a 1-year follow-up period.Twenty-one patients with spasticity due to severe ABI and no further improving with rehabilitation treatment and oral anti-spastic drugs.Repeated BT-A injections associated to a rehabilitation programme.Barthel Index (BI), Modified Ashworth Score (MAS) and VAS score for pain subjective perception were recorded.At the end of the follow-up study, MAS, BI and VAS significantly improved. Despite the number of BT-A injections, a shorter interval between severe ABI onset and first BT-A treatment correlated to a better BI improvement. None of the patients experienced adverse events attributable to BT-A.BT-A was effective and safe in the treatment of spasticity in severe ABI patients, with a better functional outcome in those subjects treated earlier after spasticity onset. The lack of correlation between clinical outcome and number of injections suggests, in addition to a direct inhibition at the neuromuscular junction, a more distant BT-A long-term effect.

Background Staphylococcus aureus is a leading cause of bacteremia, yet there remains a significant knowledge gap in the identification of relevant biomarkers that predict clinical outcomes in patients with S. aureus bacteremia. Heterogeneity in the host response to invasive S. aureus infection suggests that specific biomarker signatures could be utilized to differentiate patients prone to severe disease, thereby facilitating earlier implementation of more aggressive therapies. To further elucidate the inflammatory correlates of poor clinical outcomes in patients with S. aureus bacteremia, we evaluated the association between a panel of blood proteins at initial presentation of bacteremia and disease severity outcomes. Methods We conducted an observational study (n = 32) to evaluate the prognostic value of circulating protein biomarkers for mortality and persistent bacteremia in patients with S. aureus bloodstream infections. A case–control study of 124 patients with complicated confirmed S. aureus bloodstream infections was used to validate our findings in the observational study. Results We identified 13 candidate proteins that were correlated with mortality and persistent bacteremia by multiple comparisons. Further statistical modeling identified IL-8 and CCL2 as the strongest individual predictors of mortality, with the combination of these biomarkers having the best power to classify fatal outcome. Baseline IL-17A levels were elevated in patients with persistent bacteremia, endovascular and metastatic tissue infections. Conclusion The results demonstrate the potential utility of selected biomarkers to distinguish patients with the highest risk for treatment failure and bacteremia-related complications, providing a valuable tool for clinicians in the management of S. aureus bacteremia. Additionally, these biomarkers could identify patients with the greatest potential to benefit from novel therapies in clinical trials. Disclosures All authors: No reported disclosures.

Mitoxantrone (MTX) is an antineoplastic agent approved for treatment of secondary progressive and rapidly worsening relapsing-remitting multiple sclerosis (MS). We designed a longitudinal open-label prospective study to evaluate the efficacy and toxicity of MTX over a 2-year treatment period with a further 3-year follow-up. Fifty consecutive MS patients were included and received MTX intravenously (8 mg/m(2) every 2 months for a total of 12 infusions). Efficacy was assessed clinically and by brain MRI performed before MTX therapy, at the end of treatment and at the end of each year of follow-up. Forty-nine patients completed the 5-year study, 44 (89.8%) completed the MTX course, five (10.2%) interrupted the treatment because of side effects. Fifteen (30.6%) patients showed Expanded Disability Status Scale (EDSS) progression on treatment and nine (18.4%) during follow-up. Seventeen (34.7%) patients had enhancing lesions at baseline, nine (18.4%) at the end of treatment, but none at the end of follow-up. In conclusion, we observed EDSS progression in about 1/3 of the patients during the treatment period and in 1/5 during the further 3-year follow-up period. This evidence suggests a delayed beneficial effect after MTX treatment is completed with only a minority of patients showing disability progression once the drug was suspended.

To assess factors related to residual dizziness (RD) in patients who underwent successful canalith repositioning procedures (CRPs) for benign paroxysmal positional vertigo (BPPV).Prospective cohort study.Academic center.Ninety-seven consecutive patients with BPPV of the posterior semicircular canal were initially enrolled. Diagnosis was assessed according to clinical history and bedside evaluation. All patients were treated with CRPs until nystagmus disappeared. Three days after the successful treatment, presence of RD was investigated. If RD was present, patients were monitored every 3 days until the symptoms disappeared. Subjects who required ≥4 CRPs or who failed to meet the follow-up visit were excluded. The Dizziness Handicap Inventory (DHI) was obtained from patients at the time of diagnosis and at every subsequent visit.At the end of selection, 86 patients were included; 33 (38.36%) reported RD after successful treatment. A significant difference in the incidence of RD was observed in consideration of the age of the subjects (P = .0003) and the DHI score at the time of diagnosis (P.001). A logistic regression analysis showed that the probability of RD occurrence increased with the increase of the emotional subdomain score of the DHI questionnaire.RD is a common self-limited disorder, more frequent in the elderly, which may occur after the physical treatment for BPPV. The DHI score at the time of BPPV diagnosis represents a useful tool to quantify the impact of this vestibular disorder on the quality of life and to estimate the risk of RD after CRPs.

The objective of this study was to establish whether the time interval of 3 months is sufficient to detect whole-brain atrophy changes in patients with relapsing-remitting (RR) multiple sclerosis (MS). Another aim was to assess the value of monthly gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) and of different Gd-enhancement patterns as predictors of brain atrophy. Thirty patients with RRMS (mean disease duration 4.9 years, mean age 34.4 years and mean Expanded Disability Status Scale [EDSS] 1.4) were assessed at baseline and monthly for a period of 3 months with clinical and MRI examinations. Calculations of baseline and monthly absolute and percent changes of MRI measures have been obtained using two semiautomated (Buffalo and Trieste) and one automated (SPM99) segmentation method. Changes of brain parenchymal fraction (BPF) were investigated according to Gd-enhancement patterns. Mean absolute and percent changes of BPF did not significantly differ at any time point in the study for any of the three methods. There was slight but not significant decrease of BPF from baseline to month 3: -0.0004 (0.05%), p=0.093 for Trieste; -0.0006 (0.07%), p=0.078 for Buffalo; and -0.0006 (0.08%), p=0.081 for SPM99 method. In ring-enhancement positive patients, there was a significant difference between baseline and month 3 changes of BPF, EDSS, and number of relapses. Over the study period, we did not demonstrate differences between changes of BPF according to the presence of Gd enhancement. Longitudinally, multiple regression analysis demonstrated that the only clinical or MRI parameter that predicted BPF decrease was the mean absolute change of ring-enhancing lesion load (R=0.62, p=0.003). The noteworthy findings of this study are (1) the observation that a significant brain atrophy progression cannot be detected over a 3-month period in RRMS; (2) the demonstration that the ring-enhancement pattern may contribute to more severe brain tissue loss in the short term; and (3) the lack of relationship between the presence and duration of Gd-enhancement activity and brain volume changes in the short term.

This multi-center Italian prospective observational study reports the 4 months follow-up data of 87 patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) shifted from intravenous to subcutaneous immunoglobulin treatment. A therapeutic shift from intravenous to subcutaneous immunoglobulin was performed in 87 patients (66 CIDP; 21 MMN) affected by immune-mediated peripheral neuropathies with evidence of a sustained clinical response to intravenous immunoglobulin. Patients were evaluated by means of the Overall Neuropathy Limitation Scale, Medical Research Council Scale and Life Quality Index questionnaire, both at the time of therapeutic shift and after 4 months of subcutaneous immunoglobulin treatment. A sustained clinical efficacy was observed after the switch to subcutaneous immunoglobulin: the Overall Neuropathy Limitation Scale score improved in the group of 66 CIDP patients (P = 0.018), with only one subject reporting a worsening of 1 point, and remained stable in the group of 21 MMN patients (P = 0.841), with one subject reporting a worsening of two points. An improvement in the patient's perception of therapeutic setting was reported in both groups. This large multi-center study confirms the short-term clinical equivalence of subcutaneous versus intravenous immunoglobulin and a possible improvement in the patient's perception of therapeutic setting with the subcutaneous administration. However, further studies are required to extend the results to a longer observational period.

Objectives: To investigate whether clinical and magnetic resonance imaging (MRI) outcomes of patients with multiple sclerosis (MS) who required a reduction of administration frequency of interferon-beta (IFNB) were similar to those of patients who did not. Methods: We identified three subgroups of patients under treatment for 24 months with subcutaneous (sc) high-frequency IFNB-1a or -1b: those continuing to receive IFNB according to the drug label (recommended frequency group), those reducing the administration frequency of sc IFNB-1a or -1b (reduced frequency group), and those switched to once weekly intramuscular (im) IFNB (switched group). All patients were followed for further 24 months. The occurrence of relapse, MRI activity and disability worsening were considered as outcome measures. Results: We identified 308 patients, 201 in the recommended frequency group, 70 in the reduced frequency group, and 37 in the switched group. Patients in the reduced frequency group had increased risk for relapses (HR = 1.95, p < 0.001) and MRI activity (HR = 1.41, p < 0.001), while patients in the switched group had increased risk for relapses (HR = 1.67, p = 0.012), but not for MRI activity (HR = 1.26, p = 0.08) than those in the recommended frequency group. Predictors for disease activity re-start after the reduction of IFNB administration frequency were younger age, higher pre-IFNB relapse rate, and reducing sc IFNB frequency to twice weekly rather than switching to im IFNB-1a once weekly. Conclusion: Our findings discourage the reduction of sc IFNB administration frequency, especially in younger patients with a higher pre-IFNB relapse rate. However, switching to im IFNB-1a may be considered in some selected cases.

Myotonic dystrophy type 1 (DM1) is characterized by both a premature appearance of age-related phenotypes and multiple organ involvement, which affects skeletal and smooth muscle as well as the eye, heart, central nervous system, and endocrine system. Although erectile dysfunction (ED) is a frequent complaint in patients with DM1, it has not been investigated in great depth. Hypogonadism, which is reported to be one of the physical causes of ED in the general population, frequently occurs in DM1. We planned this case–control study to evaluate the relationship between hypogonadism, as defined by the sexual hormone profile (FSH, LH, testosterone (T) and prolactin) and ED, as assessed by means of an internationally validated self-administered questionnaire (IIEF). DM1 patients had significantly increased mean levels of both gonadotropins (FSH and LH) (p < 0.0001) and a reduced mean level of T (p < 0.0001) when compared to controls. Twelve patients were eugonadic (normal LH, T, and FSH), while 18 displayed hormonal evidence of hypogonadism, characterized by tubular failure (increased FSH) in all the subjects and associated with interstitial failure in 14 subjects: seven with primary hypogonadism (increased LH and reduced T) and seven with compensated hypogonadism (increased LH and normal T). Patients with hormonal evidence of interstitial failure had a larger CTG expansion (p = 0.008), longer disease duration (p = 0.013), higher grade of disease (p = 0.004) and lower erectile function score (p = 0.02) than eugonadic patients. Impotence occurred in 13/14 hypogonadic patients with interstitial failure and in 5/12 eugonadic patients (p = 0.017, OR = 18.2).

JO N 2912 and personal life of these patients. Hypothesizing that impotence may be an intrinsic characteristic in DM1, we performed a study to assess its frequency and characteristics. The complete series of male patients (aged 18-60 years) with genetically-confirmed DM1, under clinical surveillance in our Neuromuscular Unit in January 2005, was clinically evaluated for any disease or medication and tested with both the Mini-Mental State Examination and Hamilton Depression Rating Scale. Subjects with physical or mental diseases known to interfere with sexual activity [4] and those with congenital DM1, or cognitive dysfunction or HAM-D “severe” or “very severe” scores, were excluded. Patients are shown in Fig. 1. A total of 31 patients and 31 age-matched healthy controls filled out the questionnaire of the Internationally Validated Index of ErecGiovanni Antonini Alessandro Clemenzi Elisabetta Bucci Stefania Morino Matteo Garibaldi Micaela Sepe-Monti Franco Giubilei Giuseppe Novelli

Thalidomide is a neurotoxic immunomodulating agent currently used in Multiple Myeloma (MM). We prospectively evaluated the frequency and characteristics of peripheral neuropathy in a continuous series of 25 patients (13 M, 12 F; age 38–60, median 55 yrs) treated with thalidomide for MM. Patients underwent a neurological and neurophysiological evaluation before starting thalidomide therapy and monthly throughout duration of treatment. Sixteen patients (5 M, 11 F) developed neurophysiological characteristics of axonal sensitive damage and/or clinical peripheral neuropathy with distal sensory symptoms; treatment duration ranged between 95 and 572 days (median 298) in patients with neuropathy, and 49–264 days (median 162) in patients without neuropathy; the total amount of thalidomide taken ranged between 26 and 169 g (median 83 g) for patients with neuropathy and 13–170 g (median 51 g) for those without. In four patients, ENG alterations appeared before clinical symptoms, while in two patients they were not followed by clinical symptoms. In the remaining three patients, clinical symptoms preceded neurophysiological alterations. Age at onset of MM, disease duration before thalidomide therapy was started, total dose, duration of therapy and previous treatments were not correlated with neuropathy (multivariate logistic regression analysis). Female gender was a risk factor for developing neuropathy (OR 7.7).