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Neurology A.N Postgrad Med J (1991) 67, 509 - 531 i) The Fellowship of Postgraduate Medicine, 1991 Postgrad Med J: first published as 10.1136/pgmj.67.788.509 on 1 June 1991. Downloaded from Reviews in Medicine Neurology A.N. Gale, J.M. Gibbs, A.H.V. Schapira and P.K. Thomas Department ofNeurological Science, Royal Free Hospital School ofMedicine, RowlandHill Street, London NW3 2PF, UK Introduction The past few years have seen a significant improve- gitis, Tunkel et al.' point out that the mortality has ment in our ability to diagnose and treat neuro- not changed significantly over the last 30 years but logical diseases. New imaging techniques such as the prognosis for Gram-negative meningitis has computed tomographic (CT) scanning and magne- been markedly improved by the introduction of tic resonance imaging (MRI) have had a major third generation cephalosporins. impact on the practice ofneurology. Whilst techni- In adults and older children the commonest ques such as positron emission tomography (PET) causative organisms are Neisseria meningitidis and are mainly research orientated at present, they may Streptococcus pneumoniae and the treatment of soon find wider clinical application. New electro- choice in the UK is intravenous benzyl penicillin, physiological examinations such as magnetic brain with chloramphenicol as a second line agent. In stimulation have found use in the investigation of children aged 4 months to 6 years the most likely central motor conduction pathways. The applica- organism is Haemophilus influenzae type b which copyright. tion of the techniques of molecular biology to the may be resistant to ampicillin. Initial treatment in study of neurological disease is having a profound this age group has been chloramphenicol and effect on our understanding of the mechanisms ampicillin until sensitivities are known, but Peltona underlying these diseases. The clinical application et al.2 found that the third generation cephalos- of this knowledge is being seen in genetic counsell- porins cefotaxime and ceftriaxone were as effective ing and the diagnosis of neurodegenerative dis- as ampicillin and possibly better than chloram- orders. phenicol in a randomized comparison ofthese four The past few years have also seen major drugs in the treatment ofbacterial meningitis in 197 advances in the treatment of such diseases as children aged 3 months to 15 years. They found http://pmj.bmj.com/ epilepsy, Parkinson's disease, Guillain-Barre synd- that ceftriaxone sterilized the cerebrospinal fluid rome and migraine. Considerable work is now more rapidly than the others and discuss the being directed to effective treatment of disorders advantages and disadvantages ofeach agent rather such as Alzheimer's disease and multiple sclerosis. than expressing any firm preference. In this review, we have sought to provide an update Schaad et al.3 conducted a randomized, prospec- on selected topics chosen to cover a wide spectrum tive study comparing ceftriaxone (100 mg/kg/day ofneurological practice. They have been written to as a single daily dose) with cefuroxime (240 mg/kg/ on October 1, 2021 by guest. Protected emphasize recent advances in our understanding of day in four divided daily doses) for the treatment of the mechanisms of these diseases as well as in their bacterial meningitis in 106 children aged 6 weeks to management. 16 years. H. influenzae was the commonest infect- ing organism and N. meningitidis the next most frequent. Both drugs were clearly effective but Neurological emergencies results were better with ceftriaxone. Cerebrospinal fluid cultures were still positive at 24 hours in 6 out Thirdgeneration cephalosporins in treatment of of 52 patients treated with cefuroxime compared meningitis with one out of 52 in the ceftriaxone group, and moderate to profound hearing loss was found in 9 In a comprehensive review ofrecent advances in the of the cefuroxime treated patients and 2 of the pathophysiology and treatment ofbacterial menin- ceftriaxone group at 8 and 10 weeks after dis- charge. Moderate to severe sensorineural deafness is thought by some to be due to bacterial invasion of the cochlea. It occurs in about 10% of children Correspondence: A.H.V. Schapira, B.Sc., M.R.C.P. treated with ampicillin or chloramphenicol and is 510 A.N. GALE et al. Postgrad Med J: first published as 10.1136/pgmj.67.788.509 on 1 June 1991. Downloaded from no less common following cefuroxime. If this the authors conclude that angiography is not complication can be reduced by ceftriaxone its necessary if both CSF and CT brain scan are place in treating this serious infection can be normal. Patients who delay presentation so that recommended. these investigations cannot be done within 2 weeks of the headache may need angiography. Encephalitis Nimodipine in subarachnoid haemorrhage Herpes simplex encephalitis is uncommon, affect- ing 2 to 4 per million of the adult population per The value ofnimodipine in improving the outcome year, but it should be considered in encephalo- in patients with subarachnoid haemorrhage has pathic patients particularly if there is accompany- been confirmed by Pickard et al.7 in a randomized, ing fever, behavioural changes, focal disturbances double blind comparision of nimodipine, 60 mg or seizures. The mortality untreated is around 70% four hourly, orally, for 21 days, against placebo. and survivors are often severely impaired, but in Treatment was commenced within 96 hours of the patients treated early with acyclovir nearly 40% ictus. Cerebral infarction occurred in 61 out of 278 recover with no or little residual deficit. This (22%) patients given nimodipine, compared with subject was reviewed recently by Whitley.4 92 out of 276 (33%) patients given placebo. Poor Laboratory confirmation may be difficult and outcome, including death, vegetative state, or waiting for a demonstrable rise in antibody titres is severe residual disability at 3 months, occurred in oflittle practical help in the acute situation. Rowley 55 patients (20%) treated with minodipine and 91 et al.,5 in a preliminary report, detected herpes (33%) on placebo and the death rate was lower in simplex virus DNA in cerebrospinal fluid (CSF) by the nimodipine treated group (43 compared with using the polymerase chain reaction, in all 4 60). patients with biopsy proven herpes simplex ence- Nimodipine is a calcium-channel blocker which phalitis and in none of their 6 control patients with readily crosses the blood-brain barrier and has a other neurological diseases. This method amplifies vasodilator effect on cerebral vessels, but little very small amounts of DNA, not otherwise detect- effect on the peripheral vasculature. It was thought copyright. able, and the results are available within 2 to 3 days. that it would reduce vasospasm which is often seen It is likely to be much more reliable than CSF on angiograms following subarachnoid haemorr- culture, which is rarely informative, and is less hage. It is interesting that in this study there was no invasive than brain biopsy, particularly as CSF is apparent reduction in vasospasm, angiographic- required anyway in the emergency investigation of ally, in patients on nimodipine, and the incidence of these patients to exclude other conditions. rebleeding was slightly lower in the nimodipine group. It seems likely that nimodipine provides Subarachnoid haemorrhage andstroke some benefit directly by blocking calcium entry into neuronal cells. http://pmj.bmj.com/ Thunderclap headache Nimodipine in acute stroke Patients with proven subarachnoid haemorrhage often report recent symptoms suggesting a pre- Gelmers et al.8 reported benefit from nimodipine in vious haemorrhage - the 'warning bleed' - and in acute ischaemic stroke in a prospective controlled most cases either the patient or the doctor has not trial of 186 patients in whom treatment was started appreciated the significance ofthe symptoms at the within 24 hours of onset, but a more recent, larger, time. Conversely, it is not uncommon for patients placebo-controlled, double blind trial of oral on October 1, 2021 by guest. Protected to present with sudden severe headache where nimodipine, 120 mg/day for 21 days, has provided appropriate investigation reveals no evidence of no support for the administration of this agent subarachnoid haemorrhage. Harling et al.6 report- following acute stroke.9 Treatment was allocated ed a small but useful prospective study of 49 randomly and commenced within 48 hours ofonset patients presenting with symptoms suggesting sub- in 1215 patients over the age of 40 who were arachnoid haemorrhage. Thirty-five had haemorr- hemiparetic, conscious and able to swallow, and hage confirmed by CSF examination, CT brain had been functionally independent beforehand. scan or both. Eight of the 14 patients with both There was no difference between the nimodipine normal CSF and CT scan had angiography and this and placebo treated groups in terms ofsurvival and was negative in every case. In all 14 patients degree of independence at 7 days, 21 days and 24 follow-up for 18 to 30 months revealed no subse- weeks in the trial as a whole and no difference quent subarachnoid haemorrhage or serious between the groups in 441 patients commencing disease. Even in retrospect, it was not possible to treatment within 24 hours. identify the patients who had bled on clinical The results ofclinical trials correlate with experi- grounds alone, so investigation is important, but mental studies10 which suggest that nimodipine NEUROLOGY 511 Postgrad Med J: first published as 10.1136/pgmj.67.788.509 on 1 June 1991. Downloaded from minimizes ischaemic damage if given before or with lobar haemorrhages where hypertension was within minutes of the onset of ischaemia, but once less common. They found that at each site the an infarct has become established little benefit can prognosis was better in non-hypertensive patients be expected. or in hypertensive patients with evidence ofchronic vascular disease than in hypertensive patients with- Surgeryforprimary intracerebral haemorrhage out evidence of chronic vascular disease.
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