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At the heart of general practice since 1960

Confidentiality questions coming to your surgery

Professor Simon Shorvon reviews six new developments

in the field

of medical neurology

1. Epilepsy ­ NICE guidelines for prescribing antiepileptic drugs in adults

The recent guidelines help to clarify which antiepileptic drugs should be used and when. They also emphasise the need to try older drugs before switching to newer alternatives.

Epilepsy prescribing has over the years been rather conservative. For about three decades, since the 1960s, three drugs ­ phenytoin, carbamazepine and valproate ­ dominated therapy. But in the last 15 years a range of new antiepileptic drugs were licensed and introduced into clinical practice and there are more are on the way. The drugs were first introduced as add-on therapy for focal epilepsy in adults, because this was the group in which the clinical trials were carried out. But some are now also licensed for children and as single-drug therapy and therapeutic choice is increasing all the time.

In response to this situation, NICE recently produced guidelines on how and when to use these drugs. Although perhaps bland and predictable, the guidelines will doubtless prove influential.

They recommend the use of new drugs is restricted to those who have not benefited from the older antiepileptic drugs. In other words, the new drugs should not be used as first-line therapies, unless there are contraindications to the use of the older drugs (including drug interactions).

The guidelines also stress that there are particular issues in treating women of childbearing age due to the known teratogenic effect of some antiepileptics (and the lack of knowledge about others) but give no clear advice about choice of drugs in this situation.

2. Stroke prevention ­ the use of statins in primary and secondary prevention

New research now suggests statins reduce the risk of stroke in high-risk patients.

Previously an influential meta-analysis in 1995 (which included an impressive 45 studies and 450,000 persons followed up for 16 years) had found no association between total cholesterol level and stroke but there has since been renewed interest in the role of statins in stroke prevention.

A series of important long-term studies on the effect of statins have been recently completed. In total these studied 70,020 patients who were at high risk of coronary heart disease and have shown there is a relative and absolute risk reduction for stroke of 21 per cent and 0.9 per cent in those treated with statins.

The number of strokes prevented per 1,000 CHD patients treated for five years is nine for statins. This compares with 17 for antiplatelets and 17 for antihypertensive drugs. These studies have shown statins do in fact have favorable effects in the primary prevention of stroke in high-risk groups and also for secondary prevention.

Furthermore this effect is noticeable even in patients with normal baseline cholesterol concentrations. Whether statins are useful in the primary prevention of patients at low risk is unclear.

But in view of the findings from these studies, it is certainly reasonable to use a statin to treat patients with a history of stroke and cholesterol concentrations above 3.5mmol/dL. And statins should also be prescribed as primary prevention for patients with other vascular risk factors such as carotid atherosclerosis, diabetes, previous CHD, hypertension, smokers and those with hypercholesterolaemia.

3. Parkinson's disease ­ a new gene is discovered

It appears many common neurological diseases have a strong genetic background. Usually inheritance is complex with several genes ­ known as susceptibility genes ­ influencing the expression of the disease. These are known as complex polygenic disorders and the fact that several genes are involved explains why, in spite of clear-cut genetic influences, a family history will often be lacking. A clue to which genes may be relevant, though, comes from the rare families in which there is a strong family history.

Linkage studies in these families may identify genes that can be investigated as susceptibility genes in more typical patients with the disease. Such an approach is under way in many common neurological conditions, including epilepsy, Parksinon's disease, Alzheimer's disease and migraine.

Parkinson's is an example of a condition in which an increasing number of susceptibility genes have been discovered. Recently, a sixth gene was identified. Professor Wood's team at the Institute of Neurology in London studied three families from Italy and Spain in which multiple family members had the condition and discovered that mutations in the PINK1 gene was the cause.

The gene produces a protein, which is located in the mitochondria of cells and exerts a protective effect on the cell. Mutations of the gene may result in an increased susceptibility to cellular stress, and this is possibly how Parkinson's is caused. Studies are now under way to see if the PINK1 gene may be involved more widely in patients with Parkinson's, even if they have no obvious family history.

The authors propose that normal function of PINK1 may be to protect neurons from stress-induced mitochondrial dysfunction and apoptosis. The mutations lead to a loss of function of kinase enzymes, which are involved in the phosphorylation of mitochondrial proteins.

The next important step is to identify overlapping or converging pathways that would link other genes and pathology involved in Parkinson's.

4. Imaging ­ magnetic resonance angiography and per-operative MR

New imaging techniques are now making neurosurgery a more accurate and safer option. MRI has of course had a major impact on the practice. Brain tissue is relatively invisible to normal X-rays and the impact in the 1980s of MRI, which could differentiate grey matter, white matter and CSF, revolutionised the whole discipline.

Recent new developments include MR angiography and per-operative MRI.

MR angiography allows visualisation of intracerebral blood vessels without the need for an injection of contrast media, which can be risky and uncomfortable. Aneurysms and anomalies of the intracerebral circulation are now readily diagnosed by MR angiography, but the technology is still not sensitive enough to replace either CT or conventional angiography in the reliable diagnosis of intracranial or extracranial atherosclerosis. MR angiography has reduced the need for contrast angiograms, however, with a reduction in cost and morbidity.

Intra-operative MR is another important development, and the first intra-operative scanners are being installed. These are low field MR scanners which are sited in the operating room. The operation table can be swung sideways on tracks into the scanner allowing the surgeon to check the progress of the operation on instantly available MR scans. This means surgeons can now check if a resection of a tumour is complete or the position within the brain of a surgical target they are trying to locate. I suspect these techniques will become commonplace over the next decade.

5. Neurological infection ­ viral disease patterns are changing

Viral infections of the central nervous system are an increasing concern in neurology, not least because the geographical pattern of previously rare or exclusively tropical viral diseases seems to be changing.

An example is West Nile Virus encephalitis. Although this is currently rare in the UK or western Europe, the condition has been spreading progressively across the US where the disease resulted in more than 200 deaths in 2002.

The virus is an arbovirus (arthropod-borne) and it was probably brought into the US with an infected bird transported by plane from Israel. The neurological features include meningitis, encephalitis, and acute flaccid paralysis. Movement disorders were common acute features of WNV.

The disease has a significant mortality and sequalae include flaccid weakness, gait and movement disorders, fatigue, headache, and myalgia.

Meningitis and encephalitis are likely to have a favourable long-term outcome, but an irreversible poliomyelitis-like syndrome can result. West Nile Viral encephalitis is an example of a condition in which epidemiological surveillance is important.

The pattern of other viral diseases is also changing, most notably, from the neurological point of view, Japanese B encephalitis. Vigilance is important to avoid major outbreaks of these disabling conditions.

6. Alzheimer's ­ leading charity publishes major report

The drug treatment of Alzheimer's disease has been a controversial subject.

It is clear that the drugs do not 'cure' the condition, but do slow its progression in some patients. Some argue that the therapies are expensive and often only marginally effective. Clear-cut guidelines for treatment are needed.

In June 2004, the Alzheimer's Society published a major report ('Drugs for the treatment of Alzheimer's Disease') making its recommendations for treatment.

Drugs licensed in the UK include the anticholinestase drugs (donepezil, rivastigmine, galantamine) and a non-competitive NMDA receptor blocker (memantine). The report provides a vivid picture of the psychosocial as well as medical effects of drug treatment for this distressing condition.

The society's recommendations are:

·Patients in the early stages of the disease should be considered for treatment with anticholinesterase drugs, and with memantine when they have progressed to the moderately severe or severe stages.

·A shared-care protocol should be established in every NHS trust and this should specify how diagnosis and drug initiation should take place.

·The setting in which someone lives should not become a barrier for treatment and that those in residential and nursing care homes should not be excluded from consideration for treatment.

·If there is no positive benefit after six months, anticholinesterase drugs should not be continued, and similarly treatment with memantine should be continued only while continual efficacy is shown.

·Drug treatment should not be stopped in order to determine whether a person is benefiting from the drug treatment ('drug holidays').

And on its way....

four things we can expect to see in the next five years

1New genetic tests which can identify who is susceptible to common neurological disorders such as Alzheimer's disease and Parkinson's. While generally welcomed, these tests will also raise many ethical and practical problems.

2New surgical therapies for Parkinson's. Refinements and better understanding of deep brain stimulation and of targeted lesion surgery in Parkinson's are likely to make treatment more available to a greater number of patients who do not respond to drug therapy.

3Stem cell therapy. Major advances are likely to occur in this field, especially in the treatment of degenerative neurological disorders such as Parkinson's and Alzheimer's. But there are still formidable theoretical and practical issues to overcome first, and it seems unlikely that clinical therapy using stem cells will be available in the next five years.

4New drugs are on the horizon for Parkinson's, Alzheimer's and migraine. It is also likely that genetic testing will be able to predict which drug is most likely to suit a patient and who is most likely to suffer side-effects. In this way, drug therapy will become more effective and personalised.

Useful websites

Association of British Neurologists

Neurological Alliance

Alzheimer's Society

Brain and Spine Foundation

Epilepsy Action

Motor Neurone Disease (MND) Association

MS Society of Great Britain and Northern Ireland

The National Society for Epilepsy

Parkinson's Disease Society of the UK

The Stroke Association

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