Effects of acute paliperidone palmitate treatment in subjects with schizophrenia recently treated with oral risperidone

Objective

To examine efficacy and safety of acute treatment with paliperidone palmitate in subjects with schizophrenia whose disease remained symptomatic despite recent treatment with oral risperidone.

Methods

Post hoc analysis of a 13-week, double-blind, placebo-controlled study of subjects with symptomatic schizophrenia randomized to paliperidone palmitate 39, 156, or 234 mg (25, 100, or 150 mg equivalents of paliperidone) or placebo. Paliperidone palmitate subjects received a 234-mg day 1 dose, followed by their assigned dose on day 8 and monthly thereafter. Subjects treated with oral risperidone within 2 weeks before randomization regardless of duration were included. Assessments: PANSS, CGI-S, PSP scores; AEs. ANCOVA models with LOCF methodology evaluated treatment group differences.

Results

216 subjects received prior oral risperidone (paliperidone palmitate 39 mg, n = 53; 156 mg, n = 58; 234 mg, n = 48; placebo, n = 57). Median prior risperidone use was 22 days. Significant improvement was observed with paliperidone palmitate 156-mg or 234-mg versus placebo in least-squares mean (SE) score change at end point in PANSS total (156 mg, −15.8 [3.0], p = 0.0001; 234 mg, −17.6 [3.2], p = 0.0001), CGI-S (156 mg, −0.9 [0.2], p = 0.0068; 234 mg, −1.1 [0.2], p = 0.0003), and PSP (156 mg, 10.7 [2.3], p = 0.0061; 234 mg, 12.9 [2.4], p = 0.0009). Most common AEs (≥ 10%) in any paliperidone palmitate group were insomnia, anxiety, and headache.

Conclusions

In subjects with schizophrenia who recently received oral risperidone but who remained symptomatic, acute treatment with monthly doses of 156-mg and 234-mg paliperidone palmitate significantly improved clinical symptoms, global illness ratings, and functioning compared with placebo, with no unexpected safety findings.     

Does neurorehabilitation have a role in relapsing-remitting multiple sclerosis?

Abstract. Patients with relapsing-remitting multiple sclerosis (RR MS) often make incomplete recovery from disabling exacerbations, despite corticosteroid treatment. Inpatient rehabilitation has been shown to be valuable in progressive MS, but its role in RR MS is less clear. We evaluated the effect of rehabilitation in consecutive patients with RR MS admitted to a neurological rehabilitation unit. Outcome measures applied on admission and discharge included the Expanded Disability Status Scale (EDSS), the Barthel Index (BI) and the Functional Independence Measure (FIM), as well as a visual analogue scale (VAS) of the patients perception of rehabilitation impact. Confounding factors including the timing of steroid therapy and re-admissions were also examined. RR patients showed considerable improvement following rehabilitation, with a median change of –0.5 on EDSS, +4 on BI and +12 on FIM (mean change of –0.8 EDSS, +4.5 BI and +15.6 FIM points; effect sizes of –1.01, 0.97 and 0.86, respectively), which was significantly greater than other MS subtypes. RR patients rated their admissions highly (median VAS 8.9, interquartile range 7.5–9.9), and the VAS scores correlated modestly with disability measures (Spearmans rho = –0.42, 0.31 and 0.24 versus EDSS, BI and FIM, respectively; p = 0.007–0.040). Repeat admissions and the timing of steroid treatment did not have a significant effect on outcome. This suggests that inpatient rehabilitation is useful in RR MS, particularly in patients with incomplete recovery from relapses who have accumulated moderate to severe disability.     

A Double-Blind Comparison of Fluvoxamine Versus Placebo in the Treatment of Compulsive Buying Disorder

Nondepressed outpatients with a compulsive buying disorder were recruited by advertisement and word of mouth for inclusion in a controlled treatment trial. Following a 1-week single-blind placebo washout, subjects were randomly assigned to fluvoxamine (n = 12) or placebo (n = 11). Subjects received fluvoxamine (up to 300 mg daily) or placebo for 9 weeks. There were few dropouts. Outcome measures included the Yale–Brown Obsessive-Compulsive Scale—Shopping Version (YBOCS-SV), three Clinical Global Impressions (CGI) ratings, the Hamilton Rating Scale for Depression (HRSD), and the Maudsley Obsessive-compulsive Inventory (MOI). At the conclusion of the trial, 50% of fluvoxamine recipients and 63.6% of placebo recipients achieved CGI ratings of much or very much improvement, while 33% of fluvoxamine recipients were very much improved compared with 18% of placebo recipients (by endpoint analysis). Subjects in both treatment cells showed improvement as early as the second week of the trial, and for most, improvement continued during the 9-week study. There were no significant differences between fluvoxamine- and placebo-treated subjects on any of the outcome measures, with the exception that fluvoxamine recipients achieved greater improvement than placebo recipients on the MOI (p = .02). Adverse experiences were more frequent in the group receiving fluvoxamine, particularly nausea, insomnia, decreased motivation, and sedation. We conclude that in a short-term treatment trial of compulsive buying, subjects receiving fluvoxamine or placebo respond similarly.     

Intravenous synthetic peptide MBP8298 delayed disease progression in an HLA Class II-defined cohort of patients with progressive multiple sclerosis: results of a 24-month double-blind placebo-controlled clinical trial and 5 years of follow-up treatment

MBP8298 is a synthetic peptide with a sequence corresponding to amino acid residues 82–98 of human myelin basic protein (DENPVVHFFKNIVTPRT). It represents the immunodominant target for both B cells and T cells in multiple sclerosis (MS) patients with HLA haplotype DR2. Its administration in accordance with the principle of high dose tolerance results in long‐term suppression of anti‐myelin basic protein (MBP) autoantibody levels in the cerebrospinal fluid (CSF) of a large fraction of progressive MS patients. MBP8298 was evaluated in a 24‐month placebo‐controlled double‐blinded Phase II clinical trial in 32 patients with progressive MS. The objective was to assess the clinical efficacy of 500 mg of MBP8298 administered intravenously every 6 months, as measured by changes in Expanded Disability Status Scale (EDSS) scores. Contingency analysis for all patients at 24 months showed no significant difference between MBP8298 and placebo‐treatments (n = 32, P = 0.29). Contingency analysis in an HLA Class II defined subgroup showed a statistically significant benefit of MBP8298 treatment compared with placebo in patients with HLA haplotypes DR2 and/or DR4 (n = 20, P = 0.01). Long‐term follow‐up treatment and assessment of patients in this responder group showed a median time to progression of 78 months for MBP8298 treated patients compared with 18 months for placebo‐treatment (Kaplan–Meier analysis, P = 0.004; relative rate of progression = 0.23). Anti‐MBP autoantibody levels in the CSF of most MBP8298 treated patients were suppressed, but antibody suppression was not predictive of clinical benefit. Anti‐MBP autoantibodies that reappeared in the CSF of one patient at 36 months, whilst under treatment with MBP8298, were not reactive with the MBP8298 peptide in vitro. The identification of a responder subgroup (62.5% of the patients in this study) enables a more efficient design of a large confirmatory clinical trial of MBP8298. The probability that patients with other less common HLA‐DR haplotypes will respond to this treatment should not be ignored.     

Systemic recombinant alpha-2 interferon therapy in relapsing multiple sclerosis

This report describes the first use of recombinant-DNA-produced human interferon in patients with multiple sclerosis (MS). Ninety-eight patients who were clinically definite for MS with two or more documented exacerbations during the preceding two years were admitted to this placebo-controlled double-blind randomized trial. Although both groups were similar, placebo patients had later MS onset. Patients injected themselves with 2 X 10(6) IU of alpha-2 interferon or placebo three times each week for up to 52 weeks. This dose of interferon was well tolerated in that side effects were minimal. During the trial, the exacerbation rate was sharply reduced in both groups. In the three-month follow-up period after stopping treatment, more patients who were receiving interferon than placebo became worse neurologically. More patients who were receiving interferon than placebo changed from exacerbating MS to progressive MS during the trial. Thus, no clear therapeutic benefit of alpha-2 interferon for MS was detected.     

Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia in Japan: A 6‐week,randomized, double‐blind,placebo‐controlled study

Aim

This study aimed to evaluate the efficacy, safety, and tolerability of brexpiprazole compared to placebo in Japanese patients with acute schizophrenia (SCZ).

Methods

We conducted a 6‐week, multicenter, double‐blind, placebo‐controlled, phase 2/3 study in Japan. Patients with acute SCZ were randomized (1:1:1:1) to receive brexpiprazole 1 mg, 2 mg, 4 mg, or placebo once a day. The primary endpoint was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total scores.

Results

In the 459 patients that were randomized, brexpiprazole 2 mg showed a significant improvement versus placebo (treatment difference: ?7.32, P = 0.0124), although brexpiprazole 4 mg showed numerical improvements (treatment difference: ?3.86, P = 0.1959), and brexpiprazole 1 mg showed only minimal change (treatment difference: ?0.63, P = 0.8330). Treatment‐emergent adverse events with an incidence of ≥5% and ≥2 times the rate of placebo in the brexpiprazole groups were vomiting, elevated blood prolactin, diarrhea, nausea, and dental caries. Most treatment‐emergent adverse events were mild or moderate in severity. There were no clinically significant changes in electrocardiogram parameters, bodyweight, laboratory values, or vital signs in the brexpiprazole groups.

Conclusion

Brexpiprazole was efficacious and well tolerated in Japanese adult patients with acute SCZ.

     

Influence of adjunctive lacosamide in patients with seizures: a systematic review and meta-analysis

Introduction: Adjunctive lacosamide treatment might be promising to treat seizures. However, the results remained controversial. We conducted a systematic review and meta-analysis to compare the efficacy and safety of adjunctive lacosamide versus placebo in patients with seizures.

Methods: PubMed, EMbase, Web of science, EBSCO and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of adjunctive lacosamide versus placebo on seizures were included. Two investigators independently searched articles, extracted data and assessed the quality of included studies. The primary outcomes were 50% responder rate and seizure freedom.

Results: Four RCTs involving 1199 patients were included in the meta-analysis. Overall, compared with placebo treatment, adjunctive lacosamide treatment was associated with a significantly increased 50% responder rate (RR = 1.89; 95% CI = 1.51–2.36; P < 0.00001) and seizure freedom (RR = 4.97; 95% CI = 1.78–13.91; P = 0.002), but improved dizziness (RR = 3.97; 95% CI = 2.91–5.42; P < 0.00001), nausea (RR = 2.85; 95% CI = 1.75–4.66; P < 0.0001), vomiting (RR = 4.11; 95% CI = 2.23–7.57; P < 0.00001), diplopia (RR = 6.85; 95% CI = 3.36–13.94; P < 0.00001), treatment-emergent adverse events (RR = 2.29; 95% CI = 1.93–2.71; P < 0.00001) and serious adverse events (RR = 2.52; 95% CI = 1.33–4.78; P = 0.005).

Conclusions: Compared to placebo, adjunctive lacosamide resulted in a significantly improved 50% responder rate and seizure freedom, but with increased dizziness, nausea, vomiting, diplopia, treatment-emergent adverse events and serious adverse events.     

Soluble vascular cell adhesion molecule (VCAM) is associated with treatment effects of Interferon beta-1b in patients with Secondary Progressive Multiple Sclerosis

Abstract Background Subcutaneous IFN-1b (Betaferon^®) is an established immunomodulatory treatment for relapsing remitting MS and active secondary progressive multiple sclerosis (SPMS). It modulates cytokine and adhesion molecule expression but long term in vivo effects of IFN-1b on the immune system are not known in multiple sclerosis. Objective To address the effects of IFN-1b on serum levels for soluble adhesion molecules and cytokine receptors from MS patients. Methods Serial blood samples were obtained from 40 patients of the frequent MRI subgroup (20 patients each from the placebo and the IFN-1b treatment group), participating in the European multi-center clinical trial with IFN-1b for secondary progressive MS, at regular intervals for up to 36 months. Soluble adhesion molecules (sVCAM, sICAM-1, sL-Selectin) as well as TNF-receptor I and II were analysed in the serum of patients by enzyme linked immunosorbent assays (ELISAs). Monthly brain MRI was performed in 34 of these patients (16 patients from the placebo and 18 from the IFN-1b group) during months 1–6 and 19–24 to monitor disease activity as assessed by newly occurring gadolinium (Gd) enhancing lesions. Results An early and significant increase in sVCAM and sTNF-RII serum levels was detected in 16 out of 20 patients (80 %) treated with subcutaneous IFN-1b already at month 1 but was absent in all but one patient during placebo treatment (p<0.01). Raised sVCAM and TNF RII serum levels during months 1–6 inversely correlated with less MRI activity in the 19–24 months treatment interval in the IFNâ-1b treatment group ( p=0.0093 for TNF-RII; p=0.047 for VCAM). Conclusions sVCAM and sTNF RII levels in the serum of SPMS patients are increased during IFN-1b therapy and may at least in part explain some of the treatment effects, like reduced immune cell transmigration.     

Comparison of Levetiracetam and sodium Valproate in migraine prophylaxis: A randomized placebo-controlled study

Background:

Migraine is a chronic and disabling disorder. Treatment of migraine often comprises of symptomatic (abortive) and preventive (prophylactic) treatment. The current drugs used in migraine prophylaxis include antidepressant drugs (Serotonin Reuptake Inhibitors, Tricyclic antidepressants), and anti-epileptic drugs (valproate, gabapentin, etc).

Objective:

The objective of our study was to assess the efficacy and tolerability of levetiracetam in adult migraine prophylaxis, compared to valproate and placebo.

Materials and Methods:

We conducted a prospective, randomized, placebo-controlled study. A total of 85 patients were randomized to receive levetiracetam 500 mg/d (n = 27), valproate 500 mg/d (n = 32) or placebo (n = 26). The patients were evaluated for treatment efficacy after 6 months. Efficacy was assessed as a more than 50% decrease in headache frequency.

Results:

In levetiracetam group, 17 (63.0%) patients experienced a more than 50% decrease in headache frequency, while this efficacy number was 21 (65.6%) for valproate group and 4 (15.4%) for placebo group. The difference was not statistically significant between levetiracetam and valproate, while it was significant when comparing either levetiracetam or valproate to placebo.

Conclusion:

Compared to placebo, levetiracetam offers improvement in headache frequency in patients with migraine. The efficacy of levetiracetam in migraine prophylaxis is comparable to currently used drugs such as valproate.     

Fluoxetine for poststroke depression ——A randomized placebo controlled clinical trial

BACKGROUND: Studies have demonstrated that poststroke depression(PSD) may be related with the disequilibrium between noradrenaline and 5-hydroxytryptamine (5-HT) caused by cerebral injury. The injured regions involve noradrenergic and 5-hydroxytryptaminergic neurons as well as conduction pathway. The levels of noradrenaline and 5-HT would be decreased. OBJECTIVE: To observe the effect of fluoxetine on preventing against PSD and recovery of neurologic function, and analyze the relationship of fluoxetine and the 5-HT level. DESIGN: A randomized controlled clinical trial. SETTING: Department of Neurology, First Hospital Affiliated to Soochow University. PARTICIPANTS: Ninety consecutive patients, 47 female and 43 male, were recruited who admitted to hospital for recent stroke in the Department of Neurology, First Affiliated Hospital of Soochow University between September 2003 and February 2005. Subjects were aged (64±7 ) years, ranging from 47 to 79 years old. They all met the diagnosis criteria of various cerebrovascular diseases formulated in the 4th National Cerebrovascular Disease Conference and confirmed as stroke by skull CT or MRI; The time from onset to tentative administration was less than 7 days; The patients had clear consciousness, without obvious language disorder. They were randomized into treatment group (n =48) and placebo group (n =42). METHODS: ①All the patients were given routine treatment according to treatment guideline of cerebrovascular disease after admission. Patients in the treatment group and placebo group received 20 mg/d fluoxetine and placebo (component: vitamin C) for 8 weeks, respectively. ② Neurologic deficit was assessed according to 24-item Hamilton Rating Scale for Depression (HAMD) and Activity of Daily Living Scale (ADL) before and at 2,4 and 8 weeks after test, separately; Meanwhile, the levels of platelet 5-HT and plasma 5-HT were determined. Grading criteria of HAMD intergral depression: non-depression < 8 points; mild depression 8–20 points; moderate depression 21–35 points; severe depression > 35 points. ADL was assessed with Barthel index score (full mark 100 points). Higher points indicated better incidence and smaller dependence. Neurologic deficit score was made according to scoring criteria of neurologic deficit formulated in 1995 4th National Cerebrovascular Disease Conference: a score of 0–15 indicated a mild focal neurologic deficit, a score of 16–30 a moderate focal neurologic deficit, and a score of 31–45 a severe focal deficit. MAIN OUTCOME MEASURES: Scores of HAMD, ADL and neurologic deficit, and levels of plasma and platelet 5-HT of patients from 2 groups before, 2,4 and 8 weeks after test. RESULRS: Seventy-three of 90 randomized patients participated in the final analysis. In the treatment group, 11 patients dropped out due to insufficient clinical response (n =4), somatic side effects (n =2), intervening medical illness (n =1), hypomania (n =3), and other reasons (n =2). In the placebo group, 6 patients existed due to insufficient clinical response (n =2), somatic side effects (n =1) and other reasons (n =3). ① Before treatment, there were no significant differences in scores of HAMD, DAL and neurologic deficit in patients between two groups (P > 0.05). After 8 weeks of treatment, the scores of HAMD, DAL and neurologic deficit in the treatment group were significantly different from those in the placebo group (12.6±5.3 vs. 16.3 ±3.7; 8.6±6.4 vs. 11.2±6.4; 60.4±12.5 vs. 52.3±13.5, P < 0.01). ② After 8 weeks of treatment, platelet 5-HT level of patients in the treatment group was significantly lower than that in the placebo group [(325.3± 110.5) mg/L vs. (653.6±138.4) mg/L, P < 0.05], while there were no significant differences in plasma 5-HT between two groups (P > 0.05). CONCLUSION: Early fluoxetine treatment obviously retards PSD. The increase of platelet 5-HT level promotes the recovery of neurologic function.     

T-Lymphocyte subpopulations in multiple sclerosis —Do they help to judge immunosuppressive therapy?

Summary T-cell subpopulations were tested in multiple sclerosis (MS) patients before and after cyclophosphamide (n = 38) and corticotropin (n = 37) treatment and physiotherapy (n = 30). There were no specific changes of subset ratios immediately after immunosuppressive treatment. However, T-cell subpopulations showed great day-to-day variations in MS patients.     

Acute multiple sclerosis exacerbations are characterized by low cerebrospinal fluid suppressor/cytotoxic T-cells

The present study describes peripheral blood (PB) and CSF T-lymphocyte subpopulations in 55 MS patients with and without acute exacerbation and compares the results with those obtained from 8 with CNS infections and 45 with other neurological disorders or symptoms (OND). The MS patients were most strongly characterized by a decline of their CSF suppressor/cytotoxic T-cells, which was most profound during acute exacerbations. The proportional amount of CSF helper/inducer T-cells (Th) was higher in both MS group than in the OND group, but not different from that of the CNS infection group. No statistically significant change in the CSF Th-cells during exacerbations was seen. MS patients without an exacerbation had somewhat higher levels of their PB Th-cells than the patients with OND, but otherwise no differences in the PB T-cell subsets were seen.     

Benign and secondary progressive multiple sclerosis: a preliminary quantitative MRI study

In a preliminary study, we compared by means of quantitative magnetic resonance imaging (MRI) methods (1) the T2 values and the decay characteristics of chronic brain lesions, (2) the T2 values of normal-appearing frontal white matter (NAWM) and (3) brain lesion volumes in patients with benign and secondary progressive multiple sclerosis (MS) in order to evaluate the mechanisms underlying the development of disability. Eleven clinically definite MS patients with either benign MS (n = 5) or secondary progressive MS (n = 6) were studied. Fifty-two chronic lesions (identified by comparison with MRI scans obtained at least 12 months previously) were identified. The mean T2 of large lesions (cross-sectional area greater than 41 mm²) and of the NAWM was similar in both clinical groups. However, small lesions had higher mean T2 values (P < 0.01) in the benign group, probably at least in part because of partial volume effects. Analysis of large lesions revealed biexponential T2 relaxation in 6 of 8 secondary progressive and in 2 of 16 benign lesions, perhaps indicating a greater degree of axonal loss in large lesions of patients with secondary progressive MS. Patients with secondary progressive MS had higher (although not significant) total and infratentorial lesion loads than those of the benign group. These preliminary findings suggest, but do not establish, that variations in the extent, site and pathological nature of lesions may all contribute to different patterns of disease evolution in MS.     

Common dilemmas in couple therapy

Decreased libido and sexual dysfunction (e.g., erectile dysfunction) seem to be the most common adverse effects of long-term methadone usage. To investigate the efficacy of bupropion on sexual dysfunction in men receiving methadone maintenance therapy (MMT), a double-blind, placebo-controlled trial was conducted in the addiction quitting center of Noor and St. Aliasghar Hospital of Isfahan. Sixty male patients receiving MMT for at least six months and having complaints of sexual dysfunction were randomized to treatment (n = 30) with bupropion (200 mg/day) or placebo (n = 30) for eight weeks. Sexual function and depression scores were assessed by Arizona sexual experience scale, and Beck depression inventory II self-reported questionnaires, respectively. The results showed that bupropion could improve sexual dysfunction (P = 0.006), but it showed no effect on depression severity scale (P > 0.05). Our findings suggest that adding bupropion to the current protocols of MMT could be useful in decreasing sexual dysfunction, thus it may result in more adherence to treatment and better outcome. Further studies with control group and greater sample size are warranted to evaluate the efficacy of bupropion on improvement of each phases of sexual function among MMT patients. RCT has been registered in http://irct.ir, code: IRCT2014032616823N1.     

Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis

The accepted standard treatment of relapsing multiple sclerosis consists of medications for disease symptoms, including treatment for acute exacerbations. However, currently there is no therapy that alters the progression of physical disability associated with this disease. The purpose of this study was to determine whether interferon beta-1a could slow the progressive, irreversible, neurological disability of relapsing multiple sclerosis. Three hundred one patients with relapsing multiple sclerosis were randomized into a double-blinded, placebo-controlled, multicenter phase I11 trial of interferon beta-la. Interferon beta-la, 6.0 million units (30 μg), was administered by intramuscular injection weekly. The primary outcome variable was time to sustained disability progression of at least 1.0 point on the Kurtzke Expanded Disability Status Scale (EDSS). Interferon beta-la treatment produced a significant delay in time to sustained EDSS progression (p equals; 0.02). The Kaplan-Meier estimate of the proportion of patients progressing by the end of 104 weeks was 34.9% in the placebo group and 21.9% in the interferon beta-la-treated group. Patients treated with interferon beta-la also had significantly fewer exacerbations (p = 0.03) and a significantly lower number and volume of gadolinium-enhanced brain lesions on magnetic resonance images (pvalues ranging between 0.02 and 0.05). Over 2 years, the annual exacerbation rate was 0.90 in placebo-treated patients versus 0.61 in interferon beta-la-treated patients. There were no major adverse events related to treatment. Interferon beta- la had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity measured by gadolinium-enhanced lesions on brain magnetic resonance images. This treatment may alter the hndamen- tal course of relapsing multiple sclerosis.     

Intrathecally administered natural human fibroblast interferon reduces exacerbations of multiple sclerosis. Results of a multicenter, double-blind study

A randomized, double-blinded, placebo-controlled, two-year multicenter study demonstrated that natural human fibroblast interferon (interferon beta) administered intrathecally (IT) is effective in reducing the exacerbations of exacerbating-remitting multiple sclerosis (MS). The mean reduction in exacerbation rate of 34 patients with MS who received interferon beta administered IT was significantly greater during the study than that of 35 control patients who received placebo. The prestudy exacerbation rates were comparable for both patients who received interferon beta and control patients, but the exacerbation rate of patients receiving interferon beta at the end of the study was significantly lower than that of the control patients. Interferon beta was administered by nine or ten lumbar punctures for the first six months of the study, and observations were continued for two years. In 95% of the recipients, interferon beta therapy was well tolerated, and the side effects experienced were clearly acceptable for the benefits achieved. Low doses of indomethacin dramatically reduced the toxicity of interferon beta therapy and played an important role in successful double blinding. This study confirms a preliminary report on 20 patients that initially suggested that interferon beta administered IT was of benefit in patients with MS. The number of treatments was fewer and the dosage of interferon beta administered was less in the present study than in the preliminary one. It is possible that even fewer treatments with lower doses of interferon beta administered might provide a similar degree of prophylaxis against exacerbations.     

Incidence of varicella zoster virus infections of the central nervous system in the elderly: a large tertiary hospital-based series (2007–2014)

The aim of the study was to describe the clinical and epidemiological characteristics of the central nervous system (CNS) infection by varicella zoster virus (VZV) in patients older than 65 years in a tertiary community hospital. We retrospectively analysed the results of cerebrospinal fluid (CSF) testing in patients older than 65 years between 2007 and 2014 with clinically suspected VZV infection with CNS involvement. Patients whose CSF samples were positive for VZV DNA were included, as were those with negative results who simultaneously presented herpes zoster and CSF or magnetic resonance imaging findings suggestive of CNS infection, and in whom other possible aetiologies had been ruled out. The study included 280 patients. The disease was considered to be caused by a VZV infection in 32 patients (11.4%), of which 23 cases were virologically confirmed (detection of VZV DNA in CSF). The most frequent diagnosis of the patients with VZV CNS infection was encephalitis (83.3%), followed by meningitis (13.3%) and cerebellitis (3.3%). The mean annual incidence of VZV CNS infection was 3.0 cases per 100,000 inhabitants. VZV was the most common cause of encephalitis and viral meningitis, ahead of herpes simplex virus (n = 9). At the time of discharge, 12 (40%) patients showed neurological sequelae. Five patients (20%) died during hospitalization, all with encephalitis. Patients with a fatal outcome had significantly higher median age and longer delay before initiating acyclovir. In conclusion, VZV was the first cause of encephalitis in our elderly population. Despite acyclovir treatment, there was a high rate of case fatality and sequelae at discharge.     

CNS demyelinating disorder with mixed features of neuromyelitis optica and multiple sclerosis in HIV-1 infection. Case report and literature review

An African-American male presented with bilateral visual impairment, gait difficulties, and bladder and bowel incontinence raising concerns for multiple sclerosis (MS) or neuromyelitis optica (NMO). He was identified to be HIV-1 infected with high viral load and low CD4+ counts. Magnetic resonance imaging (MRI) of the brain was abnormal, but atypical for MS. MRI of the cervical and thoracic spinal cord showed multiple areas of myelitis with a longitudinally extensive thoracic transverse myelitis that showed enhancement with gadolinium suggestive of NMO. Cerebrospinal fluid showed oligoclonal IgG bands but did not show reactivity to aquaporin 4. Patient underwent treatment for the acute exacerbation with intravenous corticosteroids and treatment of the HIV infection with highly active antiretroviral therapy (HAART). A year later, his viral load was <20 copies/ml and CD4+ counts were normal. Vision did not significantly improve, but his ambulation improved from a near total non-ambulatory state to ambulating without aids and resolution of the bladder and bowel incontinence. A demyelinating disorder of the central nervous system (CNS) like MS or NMO has been previously reported in the context of HIV infection. The remarkable improvement of symptoms has also been previously reported with HAART, and these observations have led to clinical trials of MS with HAART therapy in the absence of HIV infection. We reviewed the few cases of CNS demyelinating disorders with HIV infection reported in the literature and speculate on the mechanisms of pathogenesis.     

Four year double-blind controlled study of levamisole in multiple sclerosis

41 patients with definite multiple sclerosis (MS) in the stationary phase entered this four year double-blind levamisole-placebo controlled study. 22 patients were treated with levamisole, 150 or 200 mg once a week for a 4 year period, and other 19 with placebo with the same schedule. Patients were put in one of the two groups at random. The treatment was then stopped for those patients who presented a clear exacerbation before the end of the 4 year trial period, and these cases have been considered as negative. Of the group treated with levamisole 8 patients presented an exacerbation during the observation period, and 14 did not. The group treated with placebo presented 14 subjects who had exacerbations and 5 patients who did not. The difference between the two groups was statistically significant. This study demonstrates that levamisole significantly reduced the number of MS patients with acute relapse during the 4 year period of treatment. Nevertheless, not all patients were free from relapse: that could probably suggest that different immunopathological backgrounds may underlie what we usually call MS.

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Sommario Quarantuno pazienti con sclerosi multipla (SM) certa sono stati introdotti in una sperimentazione in doppio cieco levamisolo/placebo mentre erano nella fase stazionaria della malattia. Ventidue di essi hanno ricevuto levamisolo, 150 o 200 mg una volta a settimana per quattro anni, ed altri 19 hanno ricevuto placebo con lo stesso schema posologico. L’assegnazione ad uno dei due gruppi è stata effettuata a caso. I pazienti che hanno presentato una chiara esacerbazione prima dello scadere dei quattro anni non hanno continuato l’assunzione e sono stati considerati come risultati negativi. Nel gruppo trattato con levamisolo 8 pazienti hanno presentato una esacerbazione e 14 no. Nel gruppo che ha ricevuto placebo 14 hanno presentato una riaccensione e 5 no. Questa differenza è risultata essere statisticamente significativa. In questo studio si dimostra che il levamisolo riduce significativamente il numero dei pazienti che presentano una esacerbazione in un periodo di 4 anni. Tuttavia il fatto che non tutti i pazienti hanno ricevuto un tale beneficio potrebbe suggerire che differenti quadri immunopatologici possono essere alla base di ciò che noi usualmente chiamiamo SM.

     

A randomized,controlled trial of aerobic exercise in combination with paroxetine in the treatment of panic disorder

Abstract

Objectives. Regular aerobic exercise (running) has been shown to be superior to a pill placebo in the treatment of panic disorder. Combined drug and exercise treatment has not been investigated in randomized controlled studies to date. Methods. This is a randomized, 10-week, controlled, parallel group, pilot study. A total of 75 outpatients with panic disorder with or without agoraphobia (DSM-IV and ICD-10) received either (1) exercise plus paroxetine 40 mg/day (n=21), (2) relaxation plus paroxetine (n=17), (3) exercise plus pill placebo (n=20), or (4) relaxation plus pill placebo (n=17). Changes in the Panic and Agoraphobia Scale (P&A), and the Clinical Global Impression Scale (CGI) underwent repeated measure analysis. Results. Effects sizes were large for all groups (d=1.53–3.87), however not significantly different. Paroxetine-treated patients were significantly more improved than placebo-treated patients. On the CGI, patients in the exercise groups (plus paroxetine or placebo) had a trend toward better improvement compared to relaxation (P=0.06). Response and remission rates were higher in the paroxetine compared to pill placebo groups. Conclusions. While paroxetine was superior to placebo, aerobic exercise did not differ from relaxation training in most efficacy measures.