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Lancet Neurology August 2006; 5:646-647
DOI:10.1016/S1474-4422(06)70509-9
News in brief
Polio outbreak in Namibia
A mass immunisation campaign is underway in Namibia after an outbreak of polio, unusually predominantly affecting adults, in the country. Namibia was free from the disease for over 10 years but on June 7, WHO annouced there were 34 suspected cases of the disease in Namibia, most in the region of the capital, Windhoek (http://www.who.int/csr/don/200...). Since then, there have been ten deaths and a further 60 suspected cases. Genetic sequencing showed that the disease originated in India and arrived in Namibia via its northern neighbour, Angola, which experienced an outbreak last year. Although no cases have been reported in Angola since November, 2005, the Namibia outbreak may signal an unknown reservoir in Angola. The greatest area of concern remains northern Nigeria, where 438 cases of polio have been reported so far this year.
Click to enlarge image
Poliovirus causing the outbreak in Namibia originated in Angola
PARK2 mutations prompt PD
The heterozygosity status of mutations in the PARK2 gene, which encodes parkin, influences the age at onset of Parkinson's disease (PD; Arch Neurol 2006; 63: 826?32). Genetic screening of at least one member from each of the 183 families with familial PD selected from the GenePD study identified 18 PARK2 mutations, four of which were previously unknown. In patients with single mutations, mean age at onset was 49?6 years. In homozygotes and compound heterozygotes, mean age at onset was 36 years. In carriers of one mutation, PD started 11?7 years earlier than in patients without mutations (p=0?04); and patients with two or more mutations had onset at 13?2 years earlier than those with only one mutation (p=0?04).
Renewed interest in kuru
Incubation periods of infection with human prions can exceed 50 years, according to findings of a surveillance study undertaken in Papua New Guinea. A team of researchers aimed to establish the prevalence of kuru, a human prion disease propagated by the practice of cannibalism in mortuary rites among the Fore people in areas of Papua New Guinea, where the disease reached epidemic proportions in the 1950s (Lancet 2006; 367: 2068?74). 11 patients with kuru were identified from July, 1996, to June, 2004. All were born before the cessation of cannibalism in the late 1950s. These data should be used to model the epidemiology of variant Creutzfeldt-Jakob disease, the authors conclude.
Pesticide exposure and PD risk
Exposure to pesticides could increase risk for Parkinson's disease (PD). A prospective analysis was done for 143 325 individuals who participated in the Cancer Prevention Study II Nutrition Cohort who did not have a diagnosis of or symptoms of PD at baseline (Ann Neurol 2006; published online June 26. DOI:10.1002/ana.20904). 7864 participants (6%) reported exposure to pesticides and incidence of PD was 70% higher in these individuals than in those not exposed (adjusted relative risk 1?7, 95% CI 1?2?2?3; p=0?002). The authors draw attention to the need to identify the specific chemicals responsible for this association.
Clozapine and metabolic syndrome
Patients with schizophrenia who take the antipsychotic clozapine, which is also used to treat psychoses in some neurodegenerative disorders, have a higher prevalence of metabolic syndrome than patients not taking the drug. Among 93 patients taking clozapine, 53?8% had metabolic syndrome compared with just 20?7% of the 2701 matched controls (Am J Psychiatry 2006; 163: 1273?76). ?Psychiatrists and other providers should consider performing regular physical health monitoring to prevent long-term adverse health consequences?, the authors conclude.
Drugs for childhood migraine
Zolmitriptan and ibuprofen are effective and well tolerated in childhood migraine attacks with mild side-effects (Neurology 2006; published online June 14. DOI:10.1212/01.wnl.0000231138....). In a double-blind, placebo-controlled, crossover study 32 children received placebo, zolmitriptan (2?5 mg), and ibuprofen (200?400 mg) to treat three consecutive migraine attacks. Pain relief after 2 h was achieved in 28% taking placebo, 62% taking zolmitriptan, and 69% taking ibuprofen (p<0?05). ?After the intake of ibuprofen, gastrointestinal side effects occurred. Zolmitriptan but not ibuprofen produced significantly more adverse events than placebo. However, both drugs are safe?, the investigators conclude.
Celecoxib in ALS
The cyclo-oxygenase-2 inhibitor celecoxib, although safe, is not effective in the treatment of patients with amyotrophic lateral sclerosis (ALS). In a double-blind, placebo-controlled clinical trial, 200 patients were treated with 800 mg/mL celecoxib, and 100 received placebo. (Ann Neurol 2006; 60: 22?31). After 1 year follow-up, celecoxib did not improve muscle strength, vital capacity, motor-unit number estimates, ALS functional rating scale-revised score, or survival. The drug was well-tolerated and did not increase adverse events, but the study did not prove its biological effect. ?Further studies of celecoxib at this dosage in patients with ALS are not warranted?, the authors conclude.
Trial preparation
Recruitment of a large sample of healthy individuals who have a gene mutation responsible for a future fatal disease is feasible. The Predict-HD Study enrolled 505 individuals at risk of Huntington's disease (HD) who had previously undergone elective DNA analyses for the CAG expansion in the HD gene and who did not have a clinical diagnosis of the disease (Arch Neurol 2006; 63: 883?90). Striatal volumes, cognitive performance, and even psychiatric rating significantly declined with motor manifestations of the disease. Data accrued from the Predict-HD study will better refine the design of clinical trials of experimental therapeutics to slow, reverse, or halt progression during the earliest period of disease.
AD pathology but no AD
Some elderly people without dementia or mild cognitive impairment have the pathological changes associated with Alzheimer's disease (AD; Neurology 2006; 66: 1837?44). 134 people without cognitive impairment, who were part of the Religious Orders Study or the Memory and Aging Project underwent brain autopsy and post-mortem assessment for Alzheimer's disease pathology. Two people (1?5%) met the National Institute of Aging-Reagan criteria for high likelihood of AD and 48 (35?8%) met criteria for intermediate likelihood; 29 (21?6%) had cerebral infarction, and 18 (13?4%) had Lewy bodies. Although not cognitively impaired, people with intermediate or high pathological likelihood of AD at autopsy had had changes in episodic memory before death.
Management of brain metastases
Whole-brain radiation therapy is commonly omitted from the initial treatment of brain metastases with stereotactic radiosurgery to avoid neurotoxicity. This precaution does not have an adverse affect on survival (JAMA 2006; 295: 2483?91). 132 patients with from one to four lesions with diameters of less than 3 cm were randomly assigned to receive surgery alone or combined with up-front radiation therapy. The results suggest that ?[stereotactic surgery] alone could be a treatment option, provided that frequent monitoring of brain tumor status is conducted?, say the authors.
Natalizumab returns
Both the US Food and Drug Adminstration and European Medicines and Evaluation Agency gave marketing approval to natalizumab for the treatment of relapsing multiple sclerosis in June. Trials of the drug were suspended in the USA last year after one confirmed, fatal case of progressive multifocal leucoencephalopathy and one suspected case in clinical-trial participants (see Lancet Neurol 2006; 5: 373). Both agencies have issued new guidance that restricts or bars use of the drug as first-line therapy.
Stick to warfarin
Oral anticoagulation should remain the therapy of choice to prevent stroke in patients with atrial fibrillation (Lancet 2006; 367: 1903?12). In the ACTIVE W trial, 3371 patients with atrial fibrillation and at least one other stroke risk factor were randomly allocated oral anticoagulation therapy or clopidogrel plus aspirin. The anticoagulation group had fewer major ischaemic events than patients on dual antiplatelet therapy (annual risk 3?93% vs 5?60%; relative risk 1?44, 95% CI 1?18?1?76; p=0?0003). This clear difference led to the trial being stopped early.
H pylori limits absorption of levodopa
Helicobacter pylori eradication in patients with Parkinson's disease increases levodopa absorption and correlates with better clinical response. In a double-blind study, 17 patients with Parkinson's disease and motor fluctuations received H pylori eradication therapy for 15 days, while 17 patients had an antioxidant (Neurology 2006; 66: 1824?29). Assessments at 2 weeks and 3 months after randomisation showed that H pylori-eradicated patients had better levodopa absorption, lower global clinical scores, and longer ?on? time duration. The authors conclude that levodopa pharmacokinetic changes after H pylori eradication may improve symptom control in patients with fluctuating responses to treatment with levodopa.
DOI:10.1016/S1474-4422(06)70509-9
News in brief
Polio outbreak in Namibia
A mass immunisation campaign is underway in Namibia after an outbreak of polio, unusually predominantly affecting adults, in the country. Namibia was free from the disease for over 10 years but on June 7, WHO annouced there were 34 suspected cases of the disease in Namibia, most in the region of the capital, Windhoek (http://www.who.int/csr/don/200...). Since then, there have been ten deaths and a further 60 suspected cases. Genetic sequencing showed that the disease originated in India and arrived in Namibia via its northern neighbour, Angola, which experienced an outbreak last year. Although no cases have been reported in Angola since November, 2005, the Namibia outbreak may signal an unknown reservoir in Angola. The greatest area of concern remains northern Nigeria, where 438 cases of polio have been reported so far this year.
Click to enlarge image
Poliovirus causing the outbreak in Namibia originated in Angola
PARK2 mutations prompt PD
The heterozygosity status of mutations in the PARK2 gene, which encodes parkin, influences the age at onset of Parkinson's disease (PD; Arch Neurol 2006; 63: 826?32). Genetic screening of at least one member from each of the 183 families with familial PD selected from the GenePD study identified 18 PARK2 mutations, four of which were previously unknown. In patients with single mutations, mean age at onset was 49?6 years. In homozygotes and compound heterozygotes, mean age at onset was 36 years. In carriers of one mutation, PD started 11?7 years earlier than in patients without mutations (p=0?04); and patients with two or more mutations had onset at 13?2 years earlier than those with only one mutation (p=0?04).
Renewed interest in kuru
Incubation periods of infection with human prions can exceed 50 years, according to findings of a surveillance study undertaken in Papua New Guinea. A team of researchers aimed to establish the prevalence of kuru, a human prion disease propagated by the practice of cannibalism in mortuary rites among the Fore people in areas of Papua New Guinea, where the disease reached epidemic proportions in the 1950s (Lancet 2006; 367: 2068?74). 11 patients with kuru were identified from July, 1996, to June, 2004. All were born before the cessation of cannibalism in the late 1950s. These data should be used to model the epidemiology of variant Creutzfeldt-Jakob disease, the authors conclude.
Pesticide exposure and PD risk
Exposure to pesticides could increase risk for Parkinson's disease (PD). A prospective analysis was done for 143 325 individuals who participated in the Cancer Prevention Study II Nutrition Cohort who did not have a diagnosis of or symptoms of PD at baseline (Ann Neurol 2006; published online June 26. DOI:10.1002/ana.20904). 7864 participants (6%) reported exposure to pesticides and incidence of PD was 70% higher in these individuals than in those not exposed (adjusted relative risk 1?7, 95% CI 1?2?2?3; p=0?002). The authors draw attention to the need to identify the specific chemicals responsible for this association.
Clozapine and metabolic syndrome
Patients with schizophrenia who take the antipsychotic clozapine, which is also used to treat psychoses in some neurodegenerative disorders, have a higher prevalence of metabolic syndrome than patients not taking the drug. Among 93 patients taking clozapine, 53?8% had metabolic syndrome compared with just 20?7% of the 2701 matched controls (Am J Psychiatry 2006; 163: 1273?76). ?Psychiatrists and other providers should consider performing regular physical health monitoring to prevent long-term adverse health consequences?, the authors conclude.
Drugs for childhood migraine
Zolmitriptan and ibuprofen are effective and well tolerated in childhood migraine attacks with mild side-effects (Neurology 2006; published online June 14. DOI:10.1212/01.wnl.0000231138....). In a double-blind, placebo-controlled, crossover study 32 children received placebo, zolmitriptan (2?5 mg), and ibuprofen (200?400 mg) to treat three consecutive migraine attacks. Pain relief after 2 h was achieved in 28% taking placebo, 62% taking zolmitriptan, and 69% taking ibuprofen (p<0?05). ?After the intake of ibuprofen, gastrointestinal side effects occurred. Zolmitriptan but not ibuprofen produced significantly more adverse events than placebo. However, both drugs are safe?, the investigators conclude.
Celecoxib in ALS
The cyclo-oxygenase-2 inhibitor celecoxib, although safe, is not effective in the treatment of patients with amyotrophic lateral sclerosis (ALS). In a double-blind, placebo-controlled clinical trial, 200 patients were treated with 800 mg/mL celecoxib, and 100 received placebo. (Ann Neurol 2006; 60: 22?31). After 1 year follow-up, celecoxib did not improve muscle strength, vital capacity, motor-unit number estimates, ALS functional rating scale-revised score, or survival. The drug was well-tolerated and did not increase adverse events, but the study did not prove its biological effect. ?Further studies of celecoxib at this dosage in patients with ALS are not warranted?, the authors conclude.
Trial preparation
Recruitment of a large sample of healthy individuals who have a gene mutation responsible for a future fatal disease is feasible. The Predict-HD Study enrolled 505 individuals at risk of Huntington's disease (HD) who had previously undergone elective DNA analyses for the CAG expansion in the HD gene and who did not have a clinical diagnosis of the disease (Arch Neurol 2006; 63: 883?90). Striatal volumes, cognitive performance, and even psychiatric rating significantly declined with motor manifestations of the disease. Data accrued from the Predict-HD study will better refine the design of clinical trials of experimental therapeutics to slow, reverse, or halt progression during the earliest period of disease.
AD pathology but no AD
Some elderly people without dementia or mild cognitive impairment have the pathological changes associated with Alzheimer's disease (AD; Neurology 2006; 66: 1837?44). 134 people without cognitive impairment, who were part of the Religious Orders Study or the Memory and Aging Project underwent brain autopsy and post-mortem assessment for Alzheimer's disease pathology. Two people (1?5%) met the National Institute of Aging-Reagan criteria for high likelihood of AD and 48 (35?8%) met criteria for intermediate likelihood; 29 (21?6%) had cerebral infarction, and 18 (13?4%) had Lewy bodies. Although not cognitively impaired, people with intermediate or high pathological likelihood of AD at autopsy had had changes in episodic memory before death.
Management of brain metastases
Whole-brain radiation therapy is commonly omitted from the initial treatment of brain metastases with stereotactic radiosurgery to avoid neurotoxicity. This precaution does not have an adverse affect on survival (JAMA 2006; 295: 2483?91). 132 patients with from one to four lesions with diameters of less than 3 cm were randomly assigned to receive surgery alone or combined with up-front radiation therapy. The results suggest that ?[stereotactic surgery] alone could be a treatment option, provided that frequent monitoring of brain tumor status is conducted?, say the authors.
Natalizumab returns
Both the US Food and Drug Adminstration and European Medicines and Evaluation Agency gave marketing approval to natalizumab for the treatment of relapsing multiple sclerosis in June. Trials of the drug were suspended in the USA last year after one confirmed, fatal case of progressive multifocal leucoencephalopathy and one suspected case in clinical-trial participants (see Lancet Neurol 2006; 5: 373). Both agencies have issued new guidance that restricts or bars use of the drug as first-line therapy.
Stick to warfarin
Oral anticoagulation should remain the therapy of choice to prevent stroke in patients with atrial fibrillation (Lancet 2006; 367: 1903?12). In the ACTIVE W trial, 3371 patients with atrial fibrillation and at least one other stroke risk factor were randomly allocated oral anticoagulation therapy or clopidogrel plus aspirin. The anticoagulation group had fewer major ischaemic events than patients on dual antiplatelet therapy (annual risk 3?93% vs 5?60%; relative risk 1?44, 95% CI 1?18?1?76; p=0?0003). This clear difference led to the trial being stopped early.
H pylori limits absorption of levodopa
Helicobacter pylori eradication in patients with Parkinson's disease increases levodopa absorption and correlates with better clinical response. In a double-blind study, 17 patients with Parkinson's disease and motor fluctuations received H pylori eradication therapy for 15 days, while 17 patients had an antioxidant (Neurology 2006; 66: 1824?29). Assessments at 2 weeks and 3 months after randomisation showed that H pylori-eradicated patients had better levodopa absorption, lower global clinical scores, and longer ?on? time duration. The authors conclude that levodopa pharmacokinetic changes after H pylori eradication may improve symptom control in patients with fluctuating responses to treatment with levodopa.
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