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New guidelines offer hope for UK patients with MS
Newsdesk New guidelines offer hope for UK patients with MS New guidelines developed by the National Collaborating Centre for Chronic Conditions in the UK should help patients with multiple sclerosis (MS) access better care by encouraging different strands of the National Health Service (NHS) to work together to improve management and treatment of the disease. The guidelines, funded by the National Institute for Clinical Excellence, have been developed to better meet the needs of patients with complex health problems that vary between individuals, focusing on how and where they should receive diagnosis, specific treatments, and rehabilitation. Several proposals in the guidelines are classified as priorities for implementation. These priorities include making specialist neurological services available to every person in the UK, rapid referrals to these services for
people with suspected MS, development of protocols between all relevant organisations in a local health area, determining whether patients with MS have any undiagnosed problems (such as depression or impaired sexual function), and putting facilities in place for patients to self-refer. Alan Thompson from the Institute of Neurology, London, UK, who was a member of the development group, welcomed the guidance and stressed the need for better collaboration between different services within the NHS and particularly for management that requires an integrated approach between health and social care. “If the guidance is translated into practice it should help patients access appropriate services, which at the moment the majority cannot”, he said, but added that very little had been done to launch the recommendations, which had been left up to charities.
Chris Polman (VU Medical Centre, Netherlands) remarked that he was very impressed by the guidance but even more so by the provision of criteria to enable measurement of quality of care. He said “many of the components addressed are not very different from the situation in the Netherlands but we don’t have a similar guidance or initiative to compare practice to guidance and improve on the basis of that”. However, Polman did not agree that there is no need to refer a patient with a suspected episode of MS to an appropriate expert until a subsequent episode occurs. Richard Rudick (Mellen Center for Multiple Sclerosis Treatment and Research, Ohio, USA) commented that the emphasis placed on communication with and treatment of the whole person is the best possible management for MS. Louise Marshall
Viral proteins cause cell death in HIV-associated dementia New research implicates viral proteins in the neurodegeneration behind HIV associated dementia (HAD) and challenges the widely held view that molecules released from macrophages and microglia are the cause neuron death. Encephalopathy affects about 20% of untreated patients with HIV, typically in the late stages of the disease. However, the lack of inflammation and the seemingly apoptotic nature of cell death make the mechanisms behind this a pathological enigma of HIV. “There is this feeling”, Roger Pomerantz (Department of Medicine, Thomas Jefferson University, PA, USA) told The Lancet Neurology, “that most of the destruction of neurons is caused by ‘evil humours’ that come out of macrophages and microglia—from proinflammatory cytokines like TNF␣ to arachidonic-acid metabolites, to various chemokines.” Pomerantz and colleagues suspected that viral proteins had an important role in neuron death leading to HIV dementia. “We did some simple THE LANCET Neurology Vol 3 June 2004
experiments to answer a simple question: what percentage of neuronal death in HIV encephalitis is due to the virus and what percentage is due to the panoply of compounds released from macrophages and microglia?” Cell-culture supernatants were extracted from macrophages and T cells infected with HIV 1. In vitro cultures of human and mouse neurons were then exposed to these virion-containing and virion-depleted supernatants and to recombinant gp120 viral protein. Although apoptosis-inducing compounds were present in the extracts of macrophages, the amount of neuron death was substantially less in the cells treated with virus-depleted supernatant, and the gp120 virus protein accounted for most of the apoptosis (Proc Natl Acad Sci USA 2004; 101: 7070–75). “This study clearly shows that neuronal apoptosis is caused by both viral proteins and factors released by macrophages/microglial cells”, says Francoise Gray (University of Paris, France), “but it stresses the major role of the virus.” The importance of virus in
http://neurology.thelancet.com
neuron death is supported, Gray says, by the fact that there is intense microglial and macrophage activation in the brain during various stages of HIV infection, in none of which is there such specific neuron damage as caused by the virus or the viral protein. The researchers identified two pathways through which the viral protein induces apoptosis: the tumour necrosis factor receptor receptor (TNFR) pathway and the Fas–Fasligand pathway. “The best neuroprotection is to stop viral replication”, says Pomerantz. Antiretrovirals can prevent replication. However, the targeting of TNFR or Fas pathways may help to combat HIV encephalitis in developing countries, where, as Pomerantz says, antiretroviral is “a bit of a dream”. The next step is to test drugs that block these pathways in vivo. Pomerantz and collegues now aim to prove that there is neurodegeneration in monkeys with simian immunodeficiency virus and to test drugs in this model. Peter Hayward
325
For personal use. Only reproduce with permission The Lancet Publishing Group.
people with suspected MS, development of protocols between all relevant organisations in a local health area, determining whether patients with MS have any undiagnosed problems (such as depression or impaired sexual function), and putting facilities in place for patients to self-refer. Alan Thompson from the Institute of Neurology, London, UK, who was a member of the development group, welcomed the guidance and stressed the need for better collaboration between different services within the NHS and particularly for management that requires an integrated approach between health and social care. “If the guidance is translated into practice it should help patients access appropriate services, which at the moment the majority cannot”, he said, but added that very little had been done to launch the recommendations, which had been left up to charities.
Chris Polman (VU Medical Centre, Netherlands) remarked that he was very impressed by the guidance but even more so by the provision of criteria to enable measurement of quality of care. He said “many of the components addressed are not very different from the situation in the Netherlands but we don’t have a similar guidance or initiative to compare practice to guidance and improve on the basis of that”. However, Polman did not agree that there is no need to refer a patient with a suspected episode of MS to an appropriate expert until a subsequent episode occurs. Richard Rudick (Mellen Center for Multiple Sclerosis Treatment and Research, Ohio, USA) commented that the emphasis placed on communication with and treatment of the whole person is the best possible management for MS. Louise Marshall
Viral proteins cause cell death in HIV-associated dementia New research implicates viral proteins in the neurodegeneration behind HIV associated dementia (HAD) and challenges the widely held view that molecules released from macrophages and microglia are the cause neuron death. Encephalopathy affects about 20% of untreated patients with HIV, typically in the late stages of the disease. However, the lack of inflammation and the seemingly apoptotic nature of cell death make the mechanisms behind this a pathological enigma of HIV. “There is this feeling”, Roger Pomerantz (Department of Medicine, Thomas Jefferson University, PA, USA) told The Lancet Neurology, “that most of the destruction of neurons is caused by ‘evil humours’ that come out of macrophages and microglia—from proinflammatory cytokines like TNF␣ to arachidonic-acid metabolites, to various chemokines.” Pomerantz and colleagues suspected that viral proteins had an important role in neuron death leading to HIV dementia. “We did some simple THE LANCET Neurology Vol 3 June 2004
experiments to answer a simple question: what percentage of neuronal death in HIV encephalitis is due to the virus and what percentage is due to the panoply of compounds released from macrophages and microglia?” Cell-culture supernatants were extracted from macrophages and T cells infected with HIV 1. In vitro cultures of human and mouse neurons were then exposed to these virion-containing and virion-depleted supernatants and to recombinant gp120 viral protein. Although apoptosis-inducing compounds were present in the extracts of macrophages, the amount of neuron death was substantially less in the cells treated with virus-depleted supernatant, and the gp120 virus protein accounted for most of the apoptosis (Proc Natl Acad Sci USA 2004; 101: 7070–75). “This study clearly shows that neuronal apoptosis is caused by both viral proteins and factors released by macrophages/microglial cells”, says Francoise Gray (University of Paris, France), “but it stresses the major role of the virus.” The importance of virus in
http://neurology.thelancet.com
neuron death is supported, Gray says, by the fact that there is intense microglial and macrophage activation in the brain during various stages of HIV infection, in none of which is there such specific neuron damage as caused by the virus or the viral protein. The researchers identified two pathways through which the viral protein induces apoptosis: the tumour necrosis factor receptor receptor (TNFR) pathway and the Fas–Fasligand pathway. “The best neuroprotection is to stop viral replication”, says Pomerantz. Antiretrovirals can prevent replication. However, the targeting of TNFR or Fas pathways may help to combat HIV encephalitis in developing countries, where, as Pomerantz says, antiretroviral is “a bit of a dream”. The next step is to test drugs that block these pathways in vivo. Pomerantz and collegues now aim to prove that there is neurodegeneration in monkeys with simian immunodeficiency virus and to test drugs in this model. Peter Hayward
325
For personal use. Only reproduce with permission The Lancet Publishing Group.