Intended for healthcare professionals

Clinical Review Recent developments

Recent developments in neurology

BMJ 2002; 324 doi: https://doi.org/10.1136/bmj.324.7338.656 (Published 16 March 2002) Cite this as: BMJ 2002;324:656

This article has a correction. Please see:

  1. Samuel Wiebe, associate professor in neurology (swiebe{at}uwo.ca),
  2. Michael W Nicolle, associate professor in neurology
  1. Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada
  1. London Health Sciences Centre, University Campus, 339 Windermere Road, London, ON, Canada N6A 5A5

    Neurology has evolved from a rich, descriptive discipline to one with many diagnostic and therapeutic options supported by an increasingly robust evidence base. This review looks at new evidence on the management of temporal lobe epilepsy, which shows that surgery can now prevent years of ineffective drug treatment and unnecessary disability. In stroke, simple clinical scales can accurately identify patients who will benefit most from evidence based treatments, although interventions of proved efficacy and safety continue to be underused. In dementia, while the promise of early preventive measures looms on the horizon, the clinical importance of available antidementia drugs continues to be investigated. Finally, the usefulness of the clinical neurological examination is being systematically analysed in specific conditions, such as migraine and carpal tunnel syndrome.

    Recent developments

    Patients with temporal lobe epilepsy should be considered for surgical treatment if more than two consecutive anticonvulsants fail to control the seizures

    The risk of stroke in patients with atrial fibrillation can be accurately predicted by the presence of risk factors such as congestive heart failure, hypertension, increased age, diabetes, and especially prior cerebral ischaemia

    Carotid endarterectomy for prevention of stroke in symptomatic carotid stenosis is more effective in patients aged over 75 than in younger patients

    Patients with ischaemic stroke who can be treated within three hours of onset should be considered for thrombolysis; larger strokes, as assessed with a simple computed tomography based scoring system, are less likely to be reversed

    Use of interferon for first demyelinating episodes may prevent progression to clinically definite multiple sclerosis

    Early corticosteroid treatment (within seven days of onset of symptoms) may be effective in Bell's palsy

    Methods

    We identified important neurological advances by canvassing subspecialty neurologists, performing hierarchical literature searches with SUMSearch (SUMSearch.UTHSCSA.edu/searchform4.htm), and reviewing medical collections such as bmj.com (www.bmj.com/collections/), Lancet Neurology Network (www.lancetneuronet.com/journal), Bandolier (www.jr2.ox.ac.uk/bandolier/), Health Technology Assessment (www.hta.nhsweb.nhs.uk/), Best Evidence 5, and the Cochrane Library. We chose topics that we judged to be of general interest and appraised the corresponding literature.

    Epilepsy

    Surgery and drugs for epilepsy

    Epilepsy affects one in 1000 people. Although seizures are easily controlled with anticonvulsants in some patients, others are refractory to drugs. Until now, it has been difficult to identify patients who will become refractory to drugs, which is important for counselling and for seeking alternative non-pharmacological treatments. A recent study found that early response to anticonvulsants is a good indicator of future control of seizures.1 Patients whose seizures are uncontrolled with the first anticonvulsant have a very low probability of being free from seizures with subsequent drugs—only 13% became free from seizures with the second drug and 4% with the third drug.

    The optimum treatment for temporal lobe epilepsy, one of the most common forms of drug resistant epilepsy, is no longer controversial. In the first randomised controlled trial comparing surgery with medical treatment, surgery was greatly superior to antiepileptic drugs. At one year, 58% of surgically treated patients and 8% of medically treated patients were free from seizures, with a number needed to treat of 2 (fig 1). Patients treated surgically also had fewer seizures and better quality of life.2 Surgery for other types of epilepsy has not been assessed in randomised controlled trials.

    Fig 1.
    Fig 1.

    Cumulative percentage of patients with temporal lobe epilepsy remaining free from disabling seizures and from any seizures at one year with surgery and with medical treatment. The number needed to treat with surgery was 2 (95% confidence interval 1 to 3) for disabling seizures and 3 (2 to 5) for any seizures

    Risk of death in epilepsy

    Clinicians and patients may misjudge the risk of death in epilepsy. Recent evidence about mortality and risk factors allows clinicians to provide better counselling to patients with epilepsy. In one study of epilepsy in children, the risk of death during the first five years after diagnosis was 7 (95% confidence interval 2.4 to 11.5) times higher than expected, and all the deaths occurred in children with neurological abnormalities (risk increased 22.9 (7.9 to 37.9) times). No deaths were attributed directly to seizures, and sudden unexplained death in epilepsy did not occur.3 In a study of patients of all ages, the age adjusted risk of death was 3.2 (2.9 to 3.5) times higher than expected.4 In another study, mortality was higher in the first few years after diagnosis and in patients with a neurological cause for their epilepsy—for example, congenital neurological abnormalities, in which the risk increased 11-12 times.5 Epilepsy was not common as a direct cause of death in these patients. In contrast, in patients with chronic, medically refractory epilepsy the cause of death was more often directly related to epilepsy. In a cohort of 393 patients undergoing surgery for epilepsy, the fivefold increase in risk of death was abolished if they became free from seizures after surgery. This underlines the importance of striving for complete freedom from seizures.6

    Cerebrovascular disease

    Atrial fibrillation and stroke

    Atrial fibrillation affects 2-5% of the general population over the age of 60, is more common in elderly people, and is associated with a stroke rate of 4-6% a year. Meta-analyses of randomised controlled trials of warfarin in non-rheumatic atrial fibrillation have shown a relative risk reduction for stroke of 60-65%, with a target international normalised ratio of 2.0-3.0, compared with an approximately 20% relative risk reduction with aspirin.7 These benefits persist despite potential haemorrhagic complications. Other risk factors significantly increase the rate of stroke with atrial fibrillation. A recent study assessed a simple six point scheme (CHADS2) for classifying stroke risk on the basis of the presence of risk factors (fig 2).8 In patients aged 65 to 95 with atrial fibrillation, the rate of stroke was 4.4 per 100 patient years. The risk adjusted rate ranged from 1.9 with 0 points to 18.2 with 6 points (fig 2). Thus aspirin alone is probably sufficient in patients with atrial fibrillation and a CHADS2 score of 0, whereas in the presence of one or more risk factors warfarin is the better choice. However, warfarin continues to be underused, especially in elderly patients, in whom atrial fibrillation and other risk factors are more common; appropriate anticoagulation was used in only 30-60% in one survey.9

    Fig 2.
    Fig 2.

    The CHADS2 scoring system for stroke in patients with atrial fibrillation, showing points assigned to risk factors (top) and the risk of stroke (with 95% confidence interval) corresponding to the number of points (bottom)

    Carotid endarterectomy for symptomatic carotid stenosis in elderly patients

    The efficacy of carotid endarterectomy for symptomatic carotid stenosis of greater than 70% is well established.10 Although the risks of carotid endarterectomy may be higher in elderly patients, the benefits are even greater.11 In patients aged over 75 who were studied in the NASCET trial, the absolute risk reduction for ipsilateral ischaemic stroke after carotid endarterectomy was 28.9% (12.9% to 44.9%), compared with 15.1% for patients aged 65-74 and 9.7% for those aged under 65.11 Surprisingly, perioperative risks of stroke and death were no higher in elderly patients.11 However, these carefully selected elderly patients might be healthier than those in the general population.

    Thrombolysis

    A meta-analysis of thrombolysis in stroke showed that patients receiving thrombolysis within six hours of the onset of symptoms were less likely to die or become dependent than were controls (odds ratio 0.83, 0.73 to 0.94), despite an increase in complications.12 Treatment within three hours of onset of symptoms produced even better results (odds ratio 0.58 for death or dependency).12 Reassuringly, administration of tissue plasminogen activator in the community had similar effectiveness, provided the recommended protocol was followed. 12 13 Complications from tissue plasminogen activator are more likely with large strokes or late treatment. 12 13 A scoring system using computed tomography, in which the amount of the middle cerebral artery territory involved was quantified, showed a good correlation between larger stroke, poorer clinical outcome, and increased risk of symptomatic intracerebral haemorrhage.14 Pending validation, this system could be used to identify patients who should not receive tissue plasminogen activator.

    Alcohol and risk of stroke

    Two recent studies showed a protective effect of light to moderate intake of alcohol on the risk of stroke. In the first study, consumption of up to two drinks a day had a protective effect for stroke (odds ratio 0.51, 0.39 to 0.67), even after adjustment for other risk factors.15 However, the risk of stroke increased with consumption of more than seven drinks a day. A second study showed that intake of more than one drink a week reduced the risk of stroke.16 The protective effect decreased with consumption of more than one drink a day.

    Dementia

    Antidementia drugs

    Few therapeutic alternatives exist for people with Alzheimer's disease. A systematic review assessed the efficacy of donepezil (1980 patients), rivastigmine (1990 patients), and galantamine (1614 patients). The studies were of good quality but short duration (<3-6 months). Donepezil and rivastigmine improved global and cognitive assessments, and galantamine at higher dosages also improved functional outcomes. Side effects were generally mild. The clinical relevance of the small but statistically significant improvements remains uncertain.17

    Statins

    Patients prescribed hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) have a reduced chance of having dementia. In a cross sectional study of patients aged 60 or over, the prevalence of dementia was 60-70% lower (P<0.001) in those prescribed statins.18 Similarly, in a case-control study of patients aged 50 or over, the risk of dementia in patients prescribed statins was one third that of those not prescribed statins (P=0.002). The benefit was independent of non-statin lipid lowering agents, cerebrovascular risk factors, and use of cardiovascular drugs.19 Could these findings signal the advent of drugs for preventing dementia? Possibly, but the current evidence cannot substantiate a direct drug effect. A randomised controlled trial currently is under way in Scotland, Ireland, and the Netherlands.20 It is investigating whether 40 mg/day of pravastatin prevents cognitive decline in 5840 people aged 70-82 years. Cognitive function is being measured annually for three years, and results are expected in 2002.

    Vaccines

    Although still at an early, experimental stage, immune therapy in Alzheimer's disease is uniquely promising. In animal models, vaccination with amyloid β prevented memory loss21 and reversed the putative brain abnormalities (amyloid deposits) of Alzheimer's disease22 without apparent toxicity. No clinical trials have yet been conducted.

    Multiple sclerosis

    Interferon for multiple sclerosis

    Although interferon decreases the frequency of relapses in multiple sclerosis, a more important question is whether it averts progression of disability. Of three randomised controlled trials, only the earliest found a benefit. At two years, disability occurred in 38.9% of patients treated with interferon and 49.7% of patients given placebo.23 Two subsequent trials involving 1499 patients failed to show any benefit on accumulating disability at two or three years. 24 25 Interferon does not seem to prevent disability in multiple sclerosis.

    About 50% of patients with a first demyelinating episode develop multiple sclerosis; interferon decreases this risk. In two randomised controlled trials, fewer patients developed clinically definitive multiple sclerosis in the interferon group than in the placebo group at two and three years. The number needed to treat to prevent clinically definite multiple sclerosis in one patient was 6 (4 to 44) at two years. 26 27

    Neuromuscular conditions

    Bell's palsy

    Although the prognosis for untreated Bell's palsy is good, 16% of patients are left with significant dysfunction of the facial nerve. An evidence based review assessed nine prospective studies of early treatment with corticosteroids in Bell's palsy.28 The methodologically strongest studies showed no benefit from corticosteroids, whereas poorer studies suggested a 1.2-fold increase in the likelihood of a good recovery and a 1.7-fold increase in complete recovery. The relative rate of improvement was 1.16 (1.05 to 1.29) after combination of class I and class II studies (see additional educational resources). Another meta-analysis found similar results.29 The evidence is hardly an overwhelming demonstration of efficacy, but as the treatment is inexpensive and brief and has a low rate of adverse effects, the early use of corticosteroids (<7 days from onset) in Bell's palsy is probably justified. The routine use of aciclovir or surgical decompression in Bell's palsy was not supported.28

    Carpal tunnel syndrome

    Carpal tunnel syndrome affects about 5% of the population. A systematic review looked at the usefulness of elements of the history and physical examination for the diagnosis of electrophysiologically proved carpal tunnel syndrome.30 Useful diagnostic findings included decreased sensation in the median nerve territory (likelihood ratio 3.1, 2.0 to 5.1), drawing of symptoms within the appropriate distribution by patients (2.4, 1.6 to 3.5), and weakness of thumb abduction (1.8, 1.4 to 2.3). Other traditional signs, including Phalen's and Tinel's signs, had little or no diagnostic value.30 There is little evidence to guide treatment of carpal tunnel syndrome. Notably, a recent prospective study that monitored the hands of 196 patients (274 hands) with untreated carpal tunnel syndrome showed spontaneous improvement rates of 27% for neurophysiological studies and 34% for symptoms.31

    Migraine

    Many patients with severe headaches carry a diagnosis of migraine, reached by themselves or by their doctors. But how is migraine diagnosed? A comprehensive review established likelihood ratios for possible diagnostic features in migraine.32 The presence of nausea was the most useful feature, while photophobia, phonophobia, exacerbation by physical activity, unilateral headache, and throbbing headache were moderately useful (table). Both precipitation of headaches by chocolate, cheese, or any food and a positive family history of migraine were specific but not sensitive diagnostic features. Features not useful for diagnosing migraine included duration of headache, precipitation by stress, missed meals, lack of sleep, changes in weather, menses, or alcohol.

    Additional educational resources

    Epilepsy
    Stroke
    Multiple sclerosis
    • National Multiple Sclerosis Society (http://164.109.172.91/), Multiple Sclerosis International Federation (www.ifmss.org.uk/)—extensive information and links on MS for professionals and the public

    Migraine
    Bell's palsy
    • Bell's palsy information site (www.bellspalsy.ws/)—good quality information for clinicians and patients

    Carpal tunnel syndrome

    Diagnostic value of various features of migraine32

    View this table:

    Acknowledgments

    We are grateful for helpful comments from Kelly Zarnke, Keith Ferguson, and Sarah Cairncross on an earlier version of this manuscript.

    Footnotes

    • Competing interests None declared.

    References

    1. 1.
    2. 2.
    3. 3.
    4. 4.
    5. 5.
    6. 6.
    7. 7.
    8. 8.
    9. 9.
    10. 10.
    11. 11.
    12. 12.
    13. 13.
    14. 14.
    15. 15.
    16. 16.
    17. 17.
    18. 18.
    19. 19.
    20. 20.
    21. 21.
    22. 22.
    23. 23.
    24. 24.
    25. 25.
    26. 26.
    27. 27.
    28. 28.
    29. 29.
    30. 30.
    31. 31.
    32. 32.