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Hughes R.A.,Center for Neuromuscular Diseases
Cochrane database of systematic reviews (Online) | Year: 2012

Guillain-Barré syndrome (GBS) is an acute paralysing disease caused by inflammation of the peripheral nerves, which corticosteroids would be expected to benefit. To examine the ability of corticosteroids to hasten recovery and reduce the long-term morbidity from GBS. We searched The Cochrane Neuromuscular Disease Group Specialized Register (1 November 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), CENTRAL (2011, Issue 4), MEDLINE (January 1966 to October 2011) and EMBASE (January 1980 to October 2011). We included randomised controlled trials (RCTs) or quasi-RCTs of any form of corticosteroid or adrenocorticotrophic hormone in GBS. Our primary outcome was change in disability grade on a seven-point scale after four weeks. Secondary outcomes included time from randomisation until recovery of unaided walking, time from randomisation until discontinuation of ventilation (for those ventilated), death, death or disability (inability to walk without aid) after 12 months, relapse, and adverse events. Two authors extracted the data independently. No new trials were discovered in the new searches in June 2009 or November 2011. Six trials with 587 participants provided data for the primary outcome. According to moderate quality evidence, the disability grade change after four weeks in the corticosteroid groups was not significantly different from that in the control groups, mean difference (MD) 0.36 less improvement (95% confidence intervals (CI) 0.16 more to 0.88 less improvement). In four trials of oral corticosteroids with 120 participants in total, there was significantly less improvement after four weeks with corticosteroids than without corticosteroids, MD 0.82 disability grades less improvement (95% CI 0.17 to 1.47). In two trials with a combined total of 467 participants, there was no significant difference, MD 0.17 (95% CI -0.06 to 0.39) of a disability grade more improvement after four weeks with intravenous corticosteroids. According to moderate to high quality evidence, there were no significant differences between the corticosteroid-treated and the control groups in any of the secondary efficacy outcomes. Diabetes was significantly more common and hypertension significantly much less common in the corticosteroid-treated participants. According to moderate quality evidence, corticosteroids given alone do not significantly hasten recovery from GBS or affect the long-term outcome. According to low quality evidence oral corticosteroids delay recovery. Diabetes requiring insulin was significantly more common and hypertension less common with corticosteroids.

Hughes R.A.,Center for Neuromuscular Diseases
Cochrane database of systematic reviews (Online) | Year: 2012

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a progressive or relapsing and remitting paralysing illness probably due to an autoimmune response which should benefit from corticosteroids. Non-randomised studies suggest that corticosteroids are beneficial. Two commonly used corticosteroids are prednisone and prednisolone. Both are usually given as oral tablets. Prednisone is converted into prednisolone in the liver so that the effect of the two drugs is usually the same. Another corticosteroid, called dexamethasone, is more potent and is used in smaller doses. To evaluate the efficacy of corticosteroid treatment compared to placebo or no treatment for CIDP and to compare the efficacy of different corticosteroid regimes. We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 February 2012), CENTRAL (2012, Issue 2), MEDLINE (January 1966 to February 2012), and EMBASE (January 1980 to February 2012) for randomised trials of corticosteroids for CIDP. We included randomised or quasi-randomised trials of treatment with any form of corticosteroids or adrenocorticotrophic hormone for CIDP, diagnosed by an internationally accepted definition. Two authors extracted the data and assessed risk of bias independently. The primary outcome was intended to be change in disability, with secondary outcomes of change in impairment, maximum motor nerve conduction velocity, or compound muscle action potential amplitude after 12 weeks, and adverse events. In one non-blinded randomised controlled trial (RCT) with 35 eligible participants, the primary outcome for this review was not available. Twelve of 19 participants treated with prednisone, compared with five of 16 participants randomised to no treatment, had improved neuropathy impairment scores after 12 weeks; the risk ratio (RR) for improvement was 2.02 (95% confidence interval (CI) 0.90 to 4.52). Adverse events were not reported in detail, but one prednisone-treated participant died.In a double-blind RCT comparing daily standard-dose oral prednisolone with monthly high-dose oral dexamethasone in 40 participants, none of the outcomes for this review were available. There were no significant differences in remission (RR 1.11; 95% CI 0.50 to 2.45 in favour of monthly dexamethasone) or change in disability or impairment after one year. Eight of 16 in the prednisolone, and seven of 24 in the dexamethasone group deteriorated. Adverse events were similar with each regimen, except that sleeplessness and moon facies (moon-shaped appearance of the face) were significantly less common with monthly dexamethasone.Experience from large non-randomised studies suggests that corticosteroids are beneficial, but long-term use causes serious side effects. Very low quality evidence from one small, randomised trial did not show a statistically significant benefit from oral prednisone compared with no treatment. Nevertheless, corticosteroids are commonly used in practice. According to moderate quality evidence from one RCT, the efficacy of high-dose monthly oral dexamethasone was not statistically different from that of daily standard-dose oral prednisolone. Most adverse events occurred with similar frequencies in both groups, but sleeplessness and moon facies were significantly less common with monthly dexamethasone. Further research is needed to identify factors which predict response.

Manji H.,Center for Neuromuscular Diseases
Handbook of Clinical Neurology | Year: 2013

Although drug-induced neuropathies account for only 2-4% of referrals, their identification is important. Numerically, chemotherapy and antiretroviral drugs are the most important worldwide. Research is currently focused on elucidating pathogenic mechanisms and the earliest presymptomatic changes using neurophysiological and pharmacogenetic techniques in order to avoid the drug or make dosage changes before irreversible damage occurs. Chemoprotectants against chemotherapy-induced neuropathy are also an active area of research. This chapter focuses on the pathophysiology of drug-induced neuropathies in general, followed by detailed reviews of neuropathy due to; newer compounds such as TNF (tumor necrosis factor) α antagonists and antibiotics such as linezolid; chemotherapeutic agents, old and new, where significant progress has been made; antiretroviral drugs; and amiodarone, which is unusual in that it causes a demyelinating neuropathy. The controversial issue of statin-induced neuropathy is also reviewed. © 2013 Elsevier B.V.

Hughes R.A.,Center for Neuromuscular Diseases
Cochrane database of systematic reviews (Online) | Year: 2013

Plasma exchange and intravenous immunoglobulin, but not corticosteroids, are beneficial in Guillain-Barré syndrome (GBS). The efficacy of other pharmacological agents is unknown. This review was first published in 2011 and this update in 2013.  To review systematically the evidence from randomised controlled trials (RCTs) for pharmacological agents other than plasma exchange, intravenous immunoglobulin and corticosteroids. On 28 August 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register CENTRAL (2012, Issue 8 in The Cochrane Library), MEDLINE (January 1966 to August 2012) and EMBASE (January 1980 to August 2012) for treatments for GBS. We considered evidence from non-randomised studies in the Discussion. We included all randomised or quasi-RCTs of acute (within four weeks from onset) GBS of all types, ages and degrees of severity. We discarded trials which only tested corticosteroids, intravenous immunoglobulin or plasma exchange. We included other pharmacological treatments or combinations of treatments compared with no treatment, placebo treatment or another treatment. Change in disability after four weeks was the primary outcome. Two authors checked references and extracted data independently. One author entered and another checked data in Review Manager (RevMan). We assessed risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions. We calculated mean differences and risk ratios with their 95% confidence intervals. We assessed strength of evidence with GradePro software. Only very low quality evidence was found for four different interventions. This update of the review found no new trials. One RCT with 13 participants showed no significant difference in any outcome between interferon beta-1a and placebo. Another with 10 participants showed no significant difference in any outcome between brain-derived neurotrophic factor and placebo. A third with 37 participants showed no significant difference in any outcome between cerebrospinal fluid filtration and plasma exchange. In a fourth with 20 participants, the risk ratio of improving by one or more disability grades after eight weeks was significantly greater with the Chinese herbal medicine tripterygium polyglycoside than with corticosteroids (risk ratio 1.47; 95% confidence interval 1.02 to 2.11). Serious adverse events were uncommon with each of these treatments and not significantly commoner in the treated than the control groups. The quality of the evidence was very low. Three small RCTs, of interferon beta-1a, brain-derived neurotrophic factor and cerebrospinal fluid filtration, showed no significant benefit or harm. A fourth small trial showed that the Chinese herbal medicine tripterygium polyglycoside hastened recovery significantly more than corticosteroids but this result needs confirmation. It was not possible to draw useful conclusions from the few observational studies.

Manji H.,Center for Neuromuscular Diseases | Jager H.R.,National Hospital for Neurology and Neurosurgery | Jager H.R.,University College London | Winston A.,Imperial College London
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2013

Neurological complications due to the HIV itself became apparent early on in the course of the AIDS epidemic. The most feared were the cognitive and motor complications termed AIDS dementia complex or HIV-associated dementia. With the introduction of combination antiretroviral therapy, the incidence of HIV-associated dementia has been dramatically reduced. However, the prevalence of less severe forms of the disorder remains around 20%. There is controversy about whether some patients may continue with progressive cognitive decline despite adequate suppression of the HIV. The salient issues are those of cerebrospinal fluid (CSF) drug penetration, drug neurotoxicity and persistent immune activation and inflammation. This review will also discuss other newly encountered complications, including the compartmentalisation (or CSF escape) and immune reconstitution inflammatory syndromes.

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