摘要:

Neurosyphilis is caused by the spirocheteTreponema pallidum. These organisms divide slowly, requiring long exposure to antibacterials for treatment success. In order for an antibacterial to be effective in the therapy of neurosyphilis, it must achieve treponemicidal concentrations in the CSF, have a long half-life and be given in a treatment regimen that favours compliance. Penicillin was first introduced for the treatment of syphilis in 1943, and despite interest in the use of amoxicillin, erythromycin, tetracycline, doxycycline, ceftriaxone and azithromycin, penicillin remains the only recommended antibacterial agent for neurosyphilis.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

The category of common sleep disorders known as parasomnias includes disorders of arousal, rapid eye movement (REM) sleep behaviour disorder (RBD), nocturnal seizures, rhythmic movement disorder, and tooth grinding or ‘bruxism’. Parasomnias are all characterised as undesirable physical or behavioural phenomena occurring during the sleep period. Although these conditions can be distressing and, in some cases, hazardous to the sleeper and his or her bed partner, it is important to recognise that parasomnias are diagnosable and treatable in the vast majority of patients.Evaluation begins with a careful clinical interview with the sleeper and a family member to elucidate the frequency, duration, description and timing after sleep onset of these behavioural events.Disorders of arousal are the most common type of parasomnia and cover a spectrum from calm sleepwalking to emotionally agitated or complex behaviours, such as dressing or driving, for which the patient usually has no memory upon awaking. ‘Sleep terrors’ are quite common in young children and are often outgrown. Disorders of arousal represent a partial, as opposed to a full, awakening from deep non-REM sleep, typically occurring within the first 60 to 90 minutes after sleep onset.RBD is characterised clinically by a history of dream-enacting behaviour, and the patient may recall dream content. REM sleep periods typically occur in the latter half of the night. Physiologically, RBD results from a lack of the normal muscle atonia that is associated with REM sleep. RBD has been linked to a number of other neurological conditions; thus, a careful review of systems and a physical examination are crucial.A formal laboratory sleep study or polysomnogram with an expanded electroencephalographic montage can help distinguish among non-REM and REM parasomnias and nocturnal seizures. The latter may manifest clinically as arousals from sleep associated with vocalisation and/or complex behaviours.Rhythmic movement disorder can include head banging or body rocking at sleep onset or during the night. Tooth grinding is a common sleep-related behaviour that, when severe, can result in dental injury. Hypnagogic hallucinations (experience of dream imagery at sleep onset) and sleep-onset paralysis (experience of muscle/body paralysis as one is falling asleep) are symptoms rather than diagnostic categories. These phenomena classically occur in many individuals with narcolepsy, but also may occur in healthy sleep-deprived individuals.Safety precautions and good general sleep hygiene measures are recommended for individuals with a parasomnia, as the disorder can be exacerbated by sleep deprivation and various other factors. When the events are frequent or particularly dramatic, medication with a long- or medium-acting benzodiazepine, such as clonazepam, at bedtime is effective therapy in most cases of non-REM disorders of arousal and RBD. A dental guard may be helpful in tooth grinders. Relaxation training and guided imagery may be helpful strategies for some patients, especially those with disorders of arousal or rhythm movement disorders. There is no evidence of any association between parasomnias and psychiatric illness. Demystification of these conditions and reassurance, particularly for parents of paediatric patients, is an important aspect of clinical intervention.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

The pathophysiology of Alzheimer's disease is complex and involves several different biochemical pathways. These include defective β-amyloid (Aβ) protein metabolism, abnormalities of glutamatergic, adrenergic, serotonergic and dopaminergic neurotransmission, and the potential involvement of inflammatory, oxidative and hormonal pathways. Consequently, these pathways are all potential targets for Alzheimer's disease treatment and prevention strategies. Currently, the mainstay treatments for Alzheimer's disease are the cholinesterase inhibitors, which increase the availability of acetylcholine at cholinergic synapses. Since the cholinesterase inhibitors confer only modest benefits, additional non-cholinergic Alzheimer's disease therapies are urgently needed.Several non-cholinergic agents are currently under development for the treatment and/or prevention of Alzheimer's disease. These include anti-amyloid strategies (e.g. immunisation, aggregation inhibitors, secretase inhibitors), transition metal chelators (e.g. clioquinol), growth factors, hormones (e.g. estradiol), herbs (e.g.Ginkgo biloba), nonsteroidal anti-inflammatory drugs (NSAIDs, e.g. indomethacin), antioxidants, lipid-lowering agents, antihypertensives, selective phosphodiesterase inhibitors, vitamins (E, B12, B6, folic acid) and agents that target neurotransmitter or neuropeptide alterations. Neurotransmitter receptor−based approaches include agents that modulate certain receptors (e.g. nicotinic, muscarinic, α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid [AMPA], γ-aminobutyric acid [GABA],N-methyl-D-aspartate [NMDA]) and agents that increase the availability of neurotransmitters (e.g. noradrenergic reuptake inhibitors).Of these strategies, the NMDA receptor antagonist memantine is in the most advanced stage of development in the US and is already approved in Europe as the first treatment for moderately severe to severe Alzheimer's disease. Memantine is proposed to counteract cellular damage due to pathological activation of NMDA receptors by glutamate. Results withGinkgo bilobahave been mixed. Data for neurotrophic therapies and vitamin E (tocopherol) appear promising but require confirmation. NSAIDs and conjugated estrogens have not proven to be of value to date for the treatment of Alzheimer's disease. Statins may have a potential role in reducing the risk or delaying the onset of Alzheimer's disease, although this has yet to be confirmed in randomised trials. There are currently no data to support the use of statins as a treatment for dementia.This article provides an update on the current status of selected agents, focusing primarily on those agents with the most extensive clinical evidence at present.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Glatiramer acetate is a synthetic copolymer composed of a random mixture of four amino acids that modifies the immune response that results in the CNS inflammation, demyelination and axonal loss characteristic of relapsing-remitting multiple sclerosis (RRMS).In three randomised, double-blind trials in patients with RRMS, subcutaneous glatiramer acetate 20 mg/day was significantly more effective than placebo for the primary outcome measure of each trial (mean relapse rate, proportion of relapse-free patients and number of gadolinium-enhancing lesions on magnetic resonance imaging [MRI] scans). The mean relapse rate was significantly reduced at endpoint (approximately one-third less) in the two larger trials (the US pivotal trial [primary endpoint] and the European/Canadian study [tertiary endpoint]) in patients receiving glatiramer acetate compared with those receiving placebo. The rate was 78% less for glatiramer acetate than placebo patients in the pilot trial that investigated a slightly different patient population. Glatiramer acetate significantly decreased disease activity and burden of disease, as assessed in the European/Canadian study using a range of MRI measures. Patients with RRMS treated with glatiramer acetate in the US trial were significantly more likely to experience improved disability (whereas placebo recipients were more likely to experience worsening disability) and their overall disability status was significantly improved compared with placebo recipients. Data from the active-treatment extension of the US trial suggest that glatiramer acetate has sustained clinical benefits up to 8 years.Glatiramer acetate was generally well tolerated; the most commonly reported treatment-related adverse events were localised injection-site reactions and transient post-injection systemic reactions. Both reactions were generally mild and self limiting but were responsible for the majority of withdrawals from treatment (up to 6.5 and 3.5%, respectively). Glatiramer acetate is not associated with the influenza-like syndrome or neutralising antibodies that are reported in patients treated with interferon-β for RRMS.The cost effectiveness of glatiramer acetate has yet to be definitively determined as assessment of available data is confounded by very different models, data sources and assumptions.ConclusionGlatiramer acetate has shown efficacy in well controlled clinical trials in patients with RRMS; it reduces relapse rate and decreases MRI-assessed disease activity and burden. It is generally well tolerated and is not associated with the influenza-like symptoms and formation of neutralising antibodies seen with the interferons-β. Based on available data and current management guidelines, glatiramer acetate is a valuable first-line treatment option for patients with RRMS.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS