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Background: Cluster headache (CH) is a comparatively rare, very severe primary headache. Although circumscript and recognisable criteria are available, the diagnosis is often missed or delayed. Besides, while adequate and [...]

Cluster headache (CH) typically presents in clusters of attacks of intense (peri)orbital, unilateral pain. The distribution of the pain implies involvement of central and/or peripheral trigeminal pathways. These can be investigated by means of trigeminal somatosensory evoked potentials (TSEP) and blink reflexes (BR). We aimed to relate functional changes in trigeminal sensory pathways to the presence of cluster periods. TSEP and BR were performed in 28 episodic CH patients during a cluster period and repeated in 22 outside a cluster period. TSEP latencies (N1, P1 and N2) and amplitude (N1-P1 and P1-N2) and BR latencies (R1, R2 ipsilateral and R2 contralateral) were compared between sides, during and outside a cluster period and with healthy control data (n = 22). During a cluster period, N2 TSEP latencies were longer on the symptomatic side compared with the non-symptomatic side (27.2 ± 3.0 ms vs. 26.3 ± 3.4 ms, P = 0.02), and compared with the same side outside the cluster period (26.7 ± 3.1 ms vs. 25.1 ± 3.0 ms, P = 0.01). N1, P1 and N2 latencies on the symptomatic side in patients during the cluster period (14.8 ± 2.3 ms, 20.4 ± 2.5 ms and 27.2 ± 3.0 ms, respectively) were significantly longer than those of healthy controls (13.4 ± 1.9 ms, 18.8 ± 2.4 ms and 25.0 ± 2.6 ms, respectively, P < 0.03). Outside the cluster period, N1 latencies of both sides (15.3 ± 2.8 ms symptomatic side and 15.4 ± 2.6 ms asymptomatic side) were longer compared with controls (13.4 ± 1.9 ms, P < 0.04). TSEP amplitudes and BR latencies revealed no significant differences. We conclude that abnormalities of the afferent trigeminal pathway are present in patients with cluster headache, most prominent during the cluster period, and on the symptomatic side. This seems primarily due of changes within the higher cerebral regions of the system. [ABSTRACT FROM AUTHOR]

Background: Pooled analyses of previous randomised studies have suggested that very early treatment with glyceryl trinitrate (also known as nitroglycerin) improves functional outcome in patients with acute ischaemic stroke or intracerebral haemorrhage, but this finding was not confirmed in a more recent trial (RIGHT-2). We aimed to assess whether patients with presumed acute stroke benefit from glyceryl tr initrate started within 3 h after symptom onset., Methods: MR ASAP was a phase 3, randomised, open-label, blinded endpoint trial done at six ambulance services serving 18 hospitals in the Netherlands. Eligible participants (aged ≥18 years) had a probable diagnosis of acute stroke (as assessed by a paramedic), a face-arm-speech-time test score of 2 or 3, systolic blood pressure of at least 140 mm Hg, and could start treatment within 3 h of symptom onset. Participants were randomly assigned (1:1) by ambulance personnel, using a secure web-based electronic application with random block sizes stratified by ambulance service, to receive either transdermal glyceryl trinitrate 5 mg/day for 24 h plus standard care (glyceryl trinitrate group) or to standard care alone (control group) in the prehospital setting. Informed consent was deferred until after arrival at the hospital. The primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) at 90 days. Safety outcomes included death within 7 days, death within 90 days, and serious adverse events. Analyses were based on modified intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. We separately analysed the total population and the target population (ie, patients with intracerebral haemorrhage, ischaemic stroke, or transient ischaemic attack). The target sample size was 1400 patients. The trial is registered as ISRCTN99503308., Findings: On June 24, 2021, the MR ASAP trial was prematurely terminated on the advice of the data and safety monitoring board, with recruitment stopped because of safety concerns in patients with intracerebral haemorrhage. Between April 4, 2018, and Feb 12, 2021, 380 patients were randomly allocated to a study group. 325 provided informed consent or died before consent could be obtained, of whom 170 were assigned to the glyceryl trinitrate group and 155 to the control group. These patients were included in the total population. 201 patients (62%) had ischaemic stroke, 34 (10%) transient ischaemic attack, 56 (17%) intracerebral haemorrhage, and 34 (10%) a stroke-mimicking condition. In the total population (n=325), the median mRS score at 90 days was 2 (IQR 1-4) in both the glyceryl trinitrate and control groups (adjusted common OR 0·97 [95% CI 0·65-1·47]). In the target population (n=291), the 90-day mRS score was 2 (2-4) in the glyceryl trinitrate group and 3 (1-4) in the control group (0·92 [0·59-1·43]). In the total population, there were no differences between the two study groups with respect to death within 90 days (adjusted OR 1·07 [0·53-2·14]) or serious adverse events (unadjusted OR 1·23 [0·76-1·99]). In patients with intracerebral haemorrhage, 12 (34%) of 35 patients allocated to glyceryl trinitrate versus two (10%) of 21 allocated to the control group died within 7 days (adjusted OR 5·91 [0·78-44·81]); death within 90 days occurred in 16 (46%) of 35 in the glyceryl trinitrate group and 11 (55%) of 20 in the control group (adjusted OR 0·87 [0·18-4·17])., Interpretation: We found no sign of benefit of transdermal glyceryl trinitrate started within 3 h of symptom onset in the prehospital setting in patients with presumed acute stroke. The signal of potential early harm of glyceryl trinitrate in patients with intracerebral haemorrhage suggests that glyceryl trinitrate should be avoided in this setting., Funding: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation., Competing Interests: Declaration of interests HR reports financial support from the European Union's Horizon 2020 research and innovation program, paid to his institution. BJE reports financial support from Health Holland Top Sector Life Sciences & Health (via the Top Consortia for Knowledge and Innovation's public–private partnership), paid to his institution; and unpaid board membership of UEMS Neuroradiology and the Dutch Society of Radiology, Division of Neuroradiology. CBLMM, DWJD, PJN and HBvdW report funding from the Dutch Heart Foundation and Stryker, all paid to their institutions or the CONTRAST consortium. CBLMM reports financial support from the TWIN Foundation and Health Evaluation Netherlands, all paid to his institution. CBLMM and HBvdW report financial support from the European Commission, all paid to their institutions. CBLMM and YBWEMR are minor shareholders of Nicolab. DWJD reports grants from Medtronic, Cerenovus, Penumbra, Brain Foundation Netherlands, ZON MW–The Netherlands Organisation for Health Research and Development, and Health Holland Top Sector Life Sciences & Health, all paid to his institution. HBvdW reports honoraria for consultancy from Bayer and LivaNova, all paid to his institution. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Many people are no longer familiar with the diseases that are part of the Dutch National Immunisation Programme (NIP). The protection given by the NIP has ensured that these diseases, most of them serious, have largely disappeared. The NIP has developed gradually, but in retrospect it was in 1957 that what we now know as the NIP started. Over the years, the NIP has gradually expanded to include various vaccines such as live attenuated vaccines, conjugate vaccines and vaccines that offer protection against chronic viral infections. Currently, the NIP offers protection against twelve different diseases. Occasionally the Netherlands still sees minor outbreaks of those diseases included in the NIP programme, generally among non-vaccinated people. It is important that the NIP is retained; stopping vaccination always leads to the return of the disease. The question is: can good protection be maintained with fewer injections? This subject is on the agenda of the Health Council Of The Netherlands for discussion in 2022.

The national vaccination rate in young children in the Netherlands has decreased in recent years. This has led to social and political discussions, for instance about compulsory vaccination for children in child-care. The national commission on child-care and vaccination has advised that vaccination should be made compulsory when the rate of vaccination has declined to a pre-determined lower threshold, to be determined by the government. A frequently quoted lower threshold is 95%. The idea behind this is the concept of a critical vaccination rate, a threshold needed for elimination of an infection in a large, well-mixed population. In this article we argue why the critical vaccination rate does not offer a scientific basis for a lower threshold to the national vaccination rate.

Introduction: In 2013, the Netherlands Pharmacovigilance Center Lareb published an overview of reports of long-lasting fatigue following bivalent HPV-vaccination (2vHPV). After an update of this overview in 2015, concerns regarding the safety of 2vHPV was picked up by the media, which led to further reports of long-lasting fatigue. Therefore, the Dutch National Institute for Public Health and the Environment (RIVM) investigated a possible association between HPV-vaccination and long-term fatigue., Methods: In this retrospective cohort study conducted in the Integrated Primary Care Information database, we investigated the occurrence of chronic fatigue syndrome (CFS), fatigue ≥6 months and 3-6 months in all girls born in 1991-2000 during the follow-up period January 1st 2007-December 31st 2014 (2007-2008 pre-vaccination and 2009-2014 post-vaccination). Patients with certain fatigue ≥6 m were asked for consent to link their primary care information with vaccination data. Incidence rates per 10,000 person years (PY) for 12-16-year-old girls were compared between pre- and post-HPV-vaccine era. A self-controlled case series (SCCS) analysis was performed using consenting vaccinated cases. A primary high-risk period of 12 months after each dose was defined., Results: The cohort consisted of 69,429 12-16-year-old girls accounting for 2758 PY pre-vaccination and 57,214 PY post-vaccination. Differences between pre- and post-vaccination incidences (CFS: 3.6 (95% CI 0.5-25.7)/10,000 PY and 0.9 (0.4-2.1); certain fatigue ≥6 m: 7.3 (1.8-29.0) and 19.4 (16.1-23.4); certain fatigue 3-6 m: 0.0 and 16.6 (13.6-20.3), respectively) were not statistically significant. SCCS analyses in 16 consenting vaccinated cases resulted in an age-adjusted RR of 0.62 (95%CI 0.07-5.49)., Conclusions: Fatigue ≥6 m and 3-6 m was frequently found among adolescent girls, but CFS was rarely diagnosed. No statistically significant increased incidence rates were found post-vaccination compared to similar age groups of girls pre-vaccination. The SCCS analysis included a low number of cases but revealed no elevated risk of certain fatigue ≥6 m in the high-risk period., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective To evaluate the presence, localization, and specificity of structural hypothalamic and whole brain changes in cluster headache and chronic paroxysmal hemicrania (CPH). Methods We compared T1-weighted magnetic resonance images of subjects with cluster headache (episodic n = 24; chronic n = 23; probable n = 14), CPH ( n = 9), migraine (with aura n = 14; without aura n = 19), and no headache ( n = 48). We applied whole brain voxel-based morphometry (VBM) using two complementary methods to analyze structural changes in the hypothalamus: region-of-interest analyses in whole brain VBM, and manual segmentation of the hypothalamus to calculate volumes. We used both conservative VBM thresholds, correcting for multiple comparisons, and less conservative thresholds for exploratory purposes. Results Using region-of-interest VBM analyses mirrored to the headache side, we found enlargement ( p < 0.05, small volume correction) in the anterior hypothalamic gray matter in subjects with chronic cluster headache compared to controls, and in all participants with episodic or chronic cluster headache taken together compared to migraineurs. After manual segmentation, hypothalamic volume (mean±SD) was larger ( p < 0.05) both in subjects with episodic (1.89 ± 0.18 ml) and chronic (1.87 ± 0.21 ml) cluster headache compared to controls (1.72 ± 0.15 ml) and migraineurs (1.68 ± 0.19 ml). Similar but non-significant trends were observed for participants with probable cluster headache (1.82 ± 0.19 ml; p = 0.07) and CPH (1.79 ± 0.20 ml; p = 0.15). Increased hypothalamic volume was primarily explained by bilateral enlargement of the anterior hypothalamus. Exploratory whole brain VBM analyses showed widespread changes in pain-modulating areas in all subjects with headache. Interpretation The anterior hypothalamus is enlarged in episodic and chronic cluster headache and possibly also in probable cluster headache or CPH, but not in migraine.

Background Familial hemiplegic migraine (FHM) is a rare monogenic migraine subtype characterised by attacks associated with transient motor weakness. Clinical information is mainly based on reports of small families with only short follow-up. Here, we document a prospective 15-year follow-up of an extended family with FHM type 2. Patients and methods After diagnosing FHM in a patient with severe attacks associated with coma and fever, we identified eight more family members with FHM and one with possible FHM. All family members were prospectively followed for 15 years. In total 13 clinically affected and 21 clinically non-affected family members were genetically tested and repeatedly investigated. Results A novel p.Arg348Pro ATP1A2 mutation was found in 14 family members: 12 with clinical FHM, one with psychomotor retardation and possible FHM, and one without FHM features. In 9/12 (75%) family members with genetically confirmed FHM, attacks were severe, long-lasting, and often associated with impaired consciousness and fever. Such attacks were frequently misdiagnosed and treated as viral meningitis or stroke. Epilepsy was reported in three family members with FHM and in the one with psychomotor retardation and possible FHM. Ataxia was not observed. Conclusion FHM should be considered in patients with recurrent coma and fever.

Background It has been hypothesized that a constitutionally narrow cavernous sinus might predispose individuals to cluster headache. Cavernous sinus dimensions, however, have never been assessed. Methods In this case-control study, we measured the dimensions of the cavernous sinus, skull base, internal carotid and pituitary gland with high-resolution T2-weighted magnetic resonance imaging in 25 episodic, 24 chronic and 13 probable cluster headache patients, 8 chronic paroxysmal hemicrania patients and 22 headache-free controls. Dimensions were compared between groups, correcting for age, sex and transcranial diameter. Results On qualitative inspection, no relevant pathology or anatomic variants that were previously associated with cluster headache or chronic paroxysmal hemicranias were observed in the cavernous sinus or paracavernous structures. The left-to-right transcranial diameter at the temporal fossa level (mean ± SD) was larger in the headache groups (episodic cluster headache: 147.5 ± 7.3 mm, p = 0.044; chronic cluster headache: 150.2 ± 7.3 mm, p < 0.001; probable cluster headache: 146.0 ± 5.3 mm, p = 0.012; and chronic paroxysmal hemicrania: 145.2 ± 9.4 mm, p = 0.044) compared with controls (140.2 ± 8.0 mm). After adjusting for transcranial diameter and correcting for multiple comparisons, there were no differences in the dimensions of the cavernous sinus and surrounding structures between headache patients and controls. Conclusion Patients with cluster headache or chronic paroxysmal hemicrania had wider skulls than headache-free controls, but the proportional dimensions of the cavernous sinus were similar.

Expectations are that 25% of the Dutch population will be aged 65 years or older in 2050 whilst in 2008 this proportion was only 15%. As a consequence the annual absolute number of new cases of specific infectious diseases will increase. Elderly people often have less clear symptoms of infection, making it harder for clinicians to recognize the disease. Morbidity and mortality caused by infections increase with age. Ageing will possibly cause an increase in levels of antibiotic resistance. There will be more elderly people in hospitals and nursing homes, where more antibiotics are used. This development will come in addition to other developments in the field of antibiotic resistance. There will be more elderly people with chronic HIV and viral hepatitis B and C infection and their complications because patients who are presently infected with those pathogens are ageing. Policy makers should more often consider introducing vaccination of older age groups against certain infectious diseases.

The Dutch Public Health Act, which came into force on 1 December 2008, replaces the existing laws concerning the combating of infectious diseases. Important changes have been incorporated in the new Public Health Act in comparison with the previous law on infectious diseases. Diseases which are probably infectious in nature and caused by as yet unknown pathogens are now notifiable, laboratories also have a nominal duty of notification and the list of notifiable diseases has been extended with 10 new infectious diseases. The provisions in the law comply with the International Health Regulations of the World Health Organization. The Centre for Infectious Disease Control Netherlands at the Dutch National Institute for Public Health and the Environment (RIVM) has issued a booklet for all Dutch physicians and laboratories providing background information on notifiable diseases. This can be useful in daily practice for helping to decide whether a disorder or cluster of infections is notifiable.

Several infectious diseases are considered to play a causal role in cancer aetiology. It is estimated that in 2003 in the Netherlands at maximum 2553 new cancer cases (3.5% of all new cancer cases) were attributable to infection. This is considerably lower than globally (17.8%) and in developed countries in general (7.7%), as previously estimated by Parkin. Most likely the explanation is that the prevalence of infections in the Netherlands is lower. Infectious agents that cause the highest number of cancer cases in the Netherlands, as well as globally, are Helicobacter pylori (stomach cancer) and the human papilloma virus (mainly cervical cancer).

Climate change is associated with changes in the occurrence of arthropod-borne diseases. It is difficult to foresee which arthropod-borne diseases will appear in the Netherlands due to climate change. Climate change influences the prevalence of ticks and may lead to a further increase in Lyme disease and an increased risk of the introduction of rickettsioses. With further warming of the climate there is a real possibility of settlement of the mosquito Aedes albopictus and introduction of the sandfly in the Netherlands. Whether this will lead to circulation of micro-organisms transmitted by these vectors (e.g. West Nile virus, Dengue virus, Leishmania) is not clear. Continued vigilance is necessary, even for vector-borne diseases that appear to be less relevant for the Netherlands.

The Netherlands' Infectious diseases Surveillance Information System (ISIS) was developed 12 years ago as an early warning system for the country. The initial objective was to establish a surveillance system that gathered the test results of all microorganisms from all medical microbiology laboratories (MMLs) in the Netherlands on a daily basis in order to create an early warning system. This paper analyses the most important results of a recent evaluation of the system. The evaluation was based on an analysis of early warning signals to detect outbreaks, number of visits to the ISIS website, and interviews with stakeholders, documentation on the ISIS system, and analyses of the ISIS MML database. While the daily collection of data on all micro-organisms for early warning has been achieved, the connection of all 85 MMLs in the Netherlands to the central ISIS MML database has not been achieved - only 18 MMLs have been connected. This has resulted in a low coverage and non-representative selection of MMLs for the Netherlands and therefore national outbreaks were missed. Data were used to determine trends in antimicrobial resistance over time. The ISIS system was not found suitable for early warning since outbreaks were detected via other systems. However, with some adaptations the ISIS system could be suitable for the surveillance of antimicrobial resistance. Furthermore, the discontinuation of this network would cause the loss of the most important data system for antimicrobial resistance in the Netherlands, since there is no other national system that gathers data on this topic. This evaluation resulted in a restart of the network.

This article describes a retrospective and descriptive study into the added value of ProMED-mail--the global electronic reporting system for outbreaks of emerging infectious diseases and toxins maintained by the International Society for Infectious Diseases--as an early warning system for The Netherlands Early Warning Committee (NEWC). Information about infectious disease events in foreign countries originating from ProMED-mail was retrieved from the reports of the NEWC between May 2006 and June 2007. Each event was analysed in depth in order to determine if it could have been a possible threat to public health in The Netherlands. It was determined whether these events were mentioned in other sources of information used by the NEWC besides ProMED-mail. In addition, we assessed the possible consequences of missing an event when not reading ProMED-mail or of being informed of the event with a time delay. Semi-structured interviews with stakeholders were conducted to explore other functions of ProMED-mail besides early warning. Five out of 25 events reported in ProMED-mail were assessed as a potential threat to The Netherlands, mainly because of the known vulnerability of The Netherlands for vaccine preventable diseases: an outbreak of measles in the United Kingdom and Japan, a case of poliomyelitis in Kenya, and two events concerning Highly Pathogenic Avian Influenza (HPAI) H5N1. The outbreak of measles in Japan and one case of HPAI H5N1 infection in a bird in Germany were only reported by ProMED-mail; the other potential threats were mentioned in other sources with a time delay. ProMED-mail has a limited but real added value over other sources in the early warning of threats. A more specific approach of using ProMED-mail by defining vulnerabilities of a country would be useful and efficient. ProMED-mail is appreciated for providing background and preliminary outbreak information.

Based on the changes in the epidemiology of infectious diseases in the Netherlands in 2000-2005, it is possible to formulate a prediction for the immediate future. Developments that one may expect with a reasonable amount of certainty are a further rise in sexually transmitted diseases, continued vulnerability for infectious diseases for which the State Vaccination Programme distributes vaccines, a slow increase in bacterial resistance, an increase in opportunistic infections, and growing risks for the introduction of new micro-organisms via international travel and trade. Much less certain are the developments surrounding avian influenza A/H5N1, ticks and mosquitoes, the rise and spread of new diseases, and bioterrorism.

Trigeminal autonomic cephalgias (TACs) include cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing. Associated structural lesions may be found, but a causal relationship is often difficult to establish. We sought to identify clinical predictors of underlying structural abnormalities by reviewing previously described and new TAC and TAC-like cases associated with a structural lesion. We found that even typical TACs can be caused by an underlying lesion. Clinical warning signs and symptoms are relatively rare. We recommend neuroimaging in all patients with a TAC or TAC-like syndrome.

In contrast with migraine, little is known about the relation between cluster headache and menstrual cycle, oral contraceptives, pregnancy, and menopause. A population based questionnaire study was performed among 224 female cluster headache patients, and the possible effect of hormonal influences on cluster headache attacks studied. For control data, a similar but adjusted questionnaire was sent to healthy volunteers and migraine patients. It was found that menstruation, use of oral contraceptives, pregnancy, and menopause had a much smaller influence on cluster headache attacks than in migraine. Cluster headache can, however, have a large impact on individual women, for example to refrain from having children.

Cluster headache (CH) is diagnosed according to criteria of the International Headache Society (IHS), but, in clinical practice, these criteria seem too restrictive. As part of a nation-wide study, we identified a group of patients who met all criteria minus one (IHS-CH-1), and assessed in which way they differed from CH patients meeting all criteria (IHS-CH). We performed a nation-wide questionnaire study for CH and CH-like syndromes, including questions based on the IHS criteria, and additional features such as restlessness during attacks, nocturnal onset of attacks, circadian rhythmicity of attacks and response to treatment. IHS-CH and IHS-CH-1 patients were compared. Of 1452 responders to two questionnaires, 1163 were IHS-CH and 289 were IHS-CH-1. The majority of the IHS-CH-1 patients were classified as such because their attacks exceeded 3 h (64%, median attack duration: 5 h), or came in a frequency of less than 1 per 2 days (16%). Age at onset was similar between the groups. The male to female ratio was 3.7 : 1 in the IHS-CH group and around 1.6 : 1 in the IHS-CH-1 groups (P < 0.005). Patients with attacks exceeding 3 h less often reported a circadian rhythmicity (IHS-CH-1: 49%, IHS-CH: 64%), episodic periodicity (IHS-CH-1: 65%, IHS-CH: 78%), nocturnal attacks (IHS-CH-1: 67%, IHS-CH: 78%), smoking (IHS-CH-1: 90%, IHS-CH: 80%) and restlessness during attacks (IHS-CH-1: 64%, IHS-CH: 76%) than IHS-CH patients (P < 0.005). Photo- or phono-phobia (IHS-CH-1: 67%, IHS-CH: 54%) and nausea (IHS-CH-1: 38%, IHS-CH: 27%) were more frequently reported by patients who reported to have attacks exceeding 3 h (P < 0.005). Similar proportions reported effect of verapamil on their attacks (IHS-CH-1: 54%, IHS-CH 61%). We conclude that average attack duration exceeding 3 h was frequently the reason for not fulfilling IHS CH criteria. Symptoms often accompanying CH such as restlessness, nocturnal attacks and an episodic attack pattern were relatively frequently present in IHS-CH-1 patients with longer attacks. These patients may therefore be diagnosed with CH. Attack frequency may not be a useful criterion for the diagnosis of CH. The upper limit of 3 h should be increased in future diagnostic criteria.

The early warning committee was established in order to recognise threats to public health caused by infectious diseases in the Netherlands in a timely and complete fashion. This article describes the outcome of a retrospective and descriptive evaluation into the completeness of the recognitions made by the early warning committee. Information about outbreaks of infectious disease in the Netherlands in 2002 and 2003, as reported in the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine), and about infectious disease events in other countries, was compared with reports of the regular weekly meetings of the Dutch early warning committee. If an outbreak or a foreign event was not mentioned in the meetings of the early warning committee, the cause for this was established. For events in other countries, it was established on the basis of whether or not the event could have been a threat to public health in the Netherlands. All outbreaks of infectious disease in the Netherlands, published or mentioned in the Nederlands Tijdschrift voor Geneeskunde were discussed by the early warning committee. Three of the events occurring in other countries in 2002 had not been discussed by the committee although, based on the criteria for a potential threat to the Netherlands, they should have been: the outbreak of avian influenza A/H5N1 in domestic fowl in Hong Kong, the increase among hospitalised patients of carriers of extended-spectrum a-lactamase producing micro-organisms in Scotland, and outbreaks of measles in several countries. In 2003, all events in other countries that could have posed a threat to the Netherlands were discussed by the early warning committee. In 2002 and 2003, the early warning committee recognised nearly all threats due to infectious diseases and outbreaks of infectious diseases which were of national importance and published in various sources of literature.

Since 2004, outbreaks of fowl plague caused by a highly pathogenic avian influenza virus of the subtype A/H5NI have been reported from various countries in Southeast Asia. To date, 118 cases with 61 deaths have been documented in humans, due to close contact with infected poultry or raw poultry meat. Although efficient human-to-human transmission has not occurred, in a few cases transmission to blood relatives could not be ruled out. In October 2005, outbreaks of A/H5NI in poultry and wild fowl have been confirmed from Turkey, Romania and Russia, due probably to infection via migratory birds. The direct risk of infection in humans in Europe is very low and is associated with direct exposure to infected poultry. In order to address the long-term risk of a pandemic due to recombination of human and avian viruses or to mutations in the avian virus itself, guidelines for pandemic preparedness have been developed and implemented in the Netherlands.

Objective: To establish whether the meetings of the so-called 'early warning committee' recognise all the threats to the public health in the Netherlands caused by infectious diseases., Design: Retrospective and descriptive evaluation., Method: The information about the outbreaks of infectious diseases in the Netherlands and about events in the area of infectious diseases in foreign countries was compared with the domestic and foreign reports discussed in the regular weekly meetings of the Dutch early warning committee. For this purpose, the authors summarized the outbreaks of infectious diseases in the Netherlands in 2002 and 2003 as reported in articles in the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine). This summary was then compared with the domestic reports discussed in the meetings of the early warning committee. If an outbreak was not mentioned in the meetings of the early warning committee, the cause for this was established. For the same period, a summary was made of the foreign events in the area of infectious diseases and this was also compared with the foreign reports mentioned in the meetings of the early warning committee. When an event had not been discussed in the meetings of the early warning committee, it was established on the basis of criteria whether the event could have been a threat to public health in the Netherlands., Results: All outbreaks of infectious diseases in the Netherlands had been discussed in the early warning committee. Of the foreign events in 2002, 3 had not been discussed in the committee although they should have been, based on the criteria for a potential threat to the Netherlands: the outbreak of avian influenza A/H5NI in domestic fowl in Hong Kong, the increase among hospitalised patients of carriers of extended-spectrum 3-lactamase producing micro-organisms in Scotland, and outbreaks of measles in several countries. In 2003, all foreign events that could have been a threat to the Netherlands were discussed in the early warning committee., Conclusion: In 2002 and 2003, the meetings of the early warning committee recognised practically all the outbreaks of and threats due to infectious diseases.

Syndromic surveillance has been developed in order to detect outbreaks of unusual infectious diseases such as severe acute respiratory syndrome (SARS) or anthrax at an early stage. Whereas the usual surveillance systems are based on established diagnoses and emergency department discharge data, syndromic surveillance uses preliminary outcomes and derived data such as absenteeism, prescription medication and requests for laboratory tests. Investigations abroad have indicated the potential ofsyndromic surveillance. In the Netherlands, the National Institute of Public Health and Environment (RIVM) is examining the feasibility of implementing syndromic surveillance.

Verapamil is an effective prophylactic treatment for cluster headaches and, therefore, is widely used. This report describes four patients with cluster headache who developed gingival enlargement after initiating treatment with verapamil. In two patients, it was possible to control this side effect adequately by optimising oral hygiene and dental plaque control. In the other two patients, lowering of the verapamil dose, in addition to optimal oral hygiene and dental plaque control, was necessary; in one patient verapamil had to be stopped completely to reverse the gingival enlargement. Doctors treating cluster headache with verapamil need to be aware of this side effect, especially as it may be preventable with good dental hygiene and dental plaque control, is reversible with reduction or cessation of verapamil, and can lead to dental loss.

Episodic brain disorders (EBD) form an intriguing group of neurological diseases in which at least some of the symptoms occur in attacks. The hypothalamus integrates many brain functions, including endocrine and autonomic control, and governs various body rhythms. It seems a likely site in which the initiation of attacks of EBD can be modulated. Indeed, the hypothalamus has a crucial role in EBD such as narcolepsy and cluster headache. The same may be true for migraine and depression. Here we summarise the evidence supporting an important role for the hypothalamus in the initiation of disease episodes in various EBD. Study of the various pathophysiological concepts of EBD within the context of the hypothalamus may prove a fruitful example of cross-fertilisation between various research areas.

Objective: To determine the risk factors that contribute to the transmission and return of scabies in health care institutions., Design: Literature analysis., Setting: Public Health Care Service Midden-Kennemerland. Heemskerk, the Netherlands., Methods: Search of Medline over the years 1976-1996 yielded 34 reports of 44 outbreaks. The contents were qualitatively examined on factors possibly contributing to the transmission and return of scabies in health care institutions., Results: Six such factors that contribute to the transmission and return of scabies in health care institutions were found: (a) among residents in health care institutions a considerable number are, once infested, at risk of developing crusted scabies, (b) many people are exposed through close contact, (c) the generally long diagnostic delay, (d) insufficient survey of the epidemiological problem, (e) treatment failures and (f) incomplete post-intervention monitoring.