Familial cluster headache: demographic patterns in affected and nonaffected.

OBJECTIVE: Smoking has been claimed to be more common in cluster headache (CH) sufferers than in nonaffected subjects. Other demographic information such as handedness, body mass index, eye color, education, occupation, and alcohol use has been described as being different in CH patients compared with a control population. The aim of this study was to get more detailed information in CH patients with a positive family history and their nonaffected relatives, assuming that there would be demographic differences between the groups. MATERIALS AND METHODS: Affected CH patients and nonaffected first- and second-degree relatives (n = 114) received a posted questionnaire. Information from 83 subjects (42 affected and 41 first- and/or second-degree relatives) from 23 families was received. P < .05 was chosen to be significant. RESULTS: Parental cigarette smoking during childhood and adolescence of patients and controls and current or former smoking was significantly more common in CH patients. Frequent alcohol intake (2-3 times/week or more) was significantly more common in the affected group of CH patients. There were significant differences as regards the life history of head trauma, but some of the affected had had the trauma after the age of onset of CH. Interestingly, CH patients worked more full-time than nonaffected. CONCLUSION: Formerly described demographic relationships in CH regarding cigarette smoking, alcohol consumption, and head trauma were also seen in our CH patients and their nonaffected relatives. These findings might represent a gene environment interaction in affected CH patients or it could be personality-lifestyle-related phenomena or a combination of these mechanisms.

Restless legs syndrome.

Restless legs syndrome (RLS) is a common neurological sensory-motor disorder that is characterized by intense restlessness and unpleasant creeping sensations deep inside the lower legs. Symptoms appear when the legs are at rest and are worst in the evening and at night. They force patients to keep moving their legs, and often to get out of bed and wander about. Periodic limb movements (PLMS) are also common during sleep amongst those suffering from RLS, and sleep efficiency is severely reduced. There are idiopathic as well as symptomatic forms of RLS, the latter being associated with e.g. pregnancy, iron deficiency and chronic renal failure. A family history of RLS is very common and pedigrees in these cases suggest an autosomal-dominant transmission with high penetrance. Genetic investigations have been performed in order to identify genes associated with RLS. Several loci have been found (on chromosomes 12q, 14q, 9p, 2q, 20p and 16p). Pathophysiology of RLS remains incompletely understood. However, advanced brain imaging studies and positive results of dopaminergic treatment suggest that RLS may be generated by dopamine dysfunction locally within the central nervous system. At present, there is a wide range of treatment options including levodopa, dopamine agonists, opioids, benzodiazepines, antiepileptic drugs and iron supplements.

Lifetime prevalence and concordance risk of cluster headache in the Swedish twin population.

OBJECTIVE: To examine the lifetime prevalence and the concordance risk of cluster headache (CH) in a twin sample representative of the Swedish general population. METHODS: The authors assessed CH as defined by the second edition of the International Classification of Headache Disorders in 31,750 registered twins born from 1935 to 1958. Structured lay screening interviews were followed by neurologist interviews of possible cases. Co-twins of affected index twins were follow-up interviewed regardless of their screening outcome. RESULTS: A total of 250 screening-positives (0.8%) were found, of which 218 (88%) were follow-up interviewed. Forty-five (21%) had the CH diagnosis verified. Among screen-negatives, hospitalization records pointed at two more verified cases and index twins at one more verified case. A total of 48 CH cases provided a crude lifetime prevalence of 151 per 100,000 (95% CI: 108, 194). The male-to-female sex ratio corresponded to 4.8 (95% CI: 2.3, 9.9). The crude lifetime prevalence of CH was higher in the twins born from 1945 to 1958 than in the twins born from 1935 to 1944 (190 vs 90/100,000). CH recurred in 2 of 12 co-twins of monozygous index twins (including 1 nonparticipant twin), whereas all co-twins of 25 dizygous index twins proved to be unaffected. CONCLUSION: As many as 1 per 500 of the general population are affected by cluster headache. Twin concordance seems low, but genetic factors may play a role for familial clustering.

Cluster headache: the history of the Cluster Club and a review of recent clinical research.

In September 2003, a scientific meeting was held in Rome to revive the International Cluster Headache Research Group (or "Cluster Club") tradition. This group of specialists was originally formed in the late 1970s by Ottar Sjaastad in order to promote research ideas, and to generate papers and other important information in this field. Its meetings, the last of which had taken place in 1994, had been informal events at which there was ample time for lively discussion. The last decade of the 20th century brought a significant increase in clinical and experimental research into cluster headache (CH), and this review summarizes some of the results of this research. The male preponderance of CH has been shown to be progressively decreasing over the years. Revised clinical criteria and a modern classification have been presented. First-degree relatives of probands with CH have been shown to have an increased risk of suffering from CH compared with the general population. Genetic analysis suggests that an autosomal dominant gene plays a role in some families. Functional neuroimaging has contributed to a better understanding of the pathophysiology of the condition. Positron emission tomography during provoked attacks has shown activation of the ipsilateral inferior posterior hypothalamus and it has been suggested that CH might be a functional neurovascular disorder of pacemaker or circadian regions in the hypothalamic grey matter. Subcutaneously administered sumatriptan has emerged as a highly effective acute treatment, but, in our opinion, the emphasis should be on attack prevention. Deep brain stimulation of the inferior posterior hypothalamic grey matter seems to be very promising as a novel treatment targeting the presumed central origin of pain attacks.

Multitracer study with positron emission tomography in Creutzfeldt-Jakob disease.

During the period February 1997 to April 2000, 15 patients with clinical symptoms of Creutzfeldt-Jakob disease (CJD) were referred to Uppsala University PET Centre. Positron emission tomography (PET) was performed to detect characteristic signs of the disease, e.g. neuronal death and/or astrocytosis in the brain. The examinations were performed in one session starting with oxygen-15 labelled water scan to measure regional cerebral blood flow, followed by imaging with the monoamine oxidase B inhibitor N-[(11)C-methyl]- L-deuterodeprenyl (DED) to assess astrocytosis in the brain and finally imaging with fluor-18 2-fluorodeoxyglucose (FDG) to assess regional cerebral glucose metabolism (rCMR(glu)) [corrected]. Nine of the patients fulfilled the clinical criteria of probable CJD. In eight of them, FDG and DED imaging revealed, in comparison with normal controls, a typical pattern characterized by a pronounced regional decrease (<2SD) in glucose brain metabolism, indicative of neuronal dysfunction; this was accompanied by a similar increase (>2SD) in DED binding, indicating astrocytosis. These changes were most pronounced in the cerebellum and the frontal, occipital and parietal cortices, whereas the pons, the thalamus and the putamen were less affected and the temporal cortex appeared unaffected. The cerebral blood flow showed a pattern similar to that observed with FDG. In the ninth patient, analysis with DED was not possible. The diagnosis of definite CJD according to international consensus criteria was confirmed in six of these patients. In one patient with probable CJD, protease-resistant prion protein (PrPres) could not be demonstrated. In two patients with probable CJD, autopsy was not allowed. Computed tomography and magnetic resonance imaging, performed in four and seven of these nine patients respectively, showed unspecific, mainly atrophic changes. In six other patients, the PET examinations gave a different pattern. In three of them, high rCMR(glu) was noticed in parts of the brain, particularly in the temporal lobes and basal ganglia, which could suggest encephalitis. One of the patients had Sjögren's syndrome, one had paraneoplastic limbic encephalitis and the third recovered spontaneously. In the other three patients, the DED binding was normal despite a hypometabolic glucose pattern. In conclusion, the PET findings obtained using DED and FDG paralleled neuropathological findings indicating neuronal dysfunction and astrocytosis, changes that are found in CJD.

Lifetime prevalence and characteristics of recurrent primary headaches in a population-based sample of Swedish twins.

OBJECTIVE: To examine the lifetime prevalence and other characteristics of recurrent primary headaches in twins. BACKGROUND: The twin model may provide insights into the role of genetic and environmental influences in headache disorders. However, assumptions as to whether twins are representative of the general population, and whether monozygotic and dizygotic twins are similar have rarely been addressed. METHODS: The study population consisted of a random sample of 17- to 82-year-old twins from the Swedish Twin Registry (n = 1329). Structured interviews on the telephone by lay personnel and the International Headache Society criteria were used for assessment and diagnosis of recurrent primary headaches. Prevalence data of the general population for migraine and tension-type headache was obtained from various published reports. RESULTS: A total of 372 subjects (29%) had ever had recurrent headaches. In total, 241 recurrent headache sufferers fulfilled the criteria for migraine or tension-type headache, and the lifetime prevalence was 7.1% for migraine without aura, 1.4% for migraine always with aura, 1.9% for migraine occasionally with aura, 9.4% for episodic tension-type headache, and 1.3% for chronic tension-type headache. The lifetime prevalence of all migraine and all tension-type headache, including another 84 subjects fulfilling all but one of the criteria for migraine or tension-type headache, was 13.8% and 13.5%, respectively. The corresponding prevalence risk for women was 2.4 (95% confidence interval [CI] 1.7, 3.4) and 1.5 (95% CI 1.1, 2.1), respectively. Zygosity was not a significant predictor for migraine. In tension-type headache, the prevalence risk for dizygotic twins and unlike-sexed twins as compared with monozygotic twins was 1.9 (95% CI: 1.2, 3.1) and 1.8 (95% CI: 1.1, 2.9), respectively. CONCLUSION: There is no twin-singleton or monozygotic-dizygotic difference for the risk of migraine. In tension-type headache, twins seem to have a lower risk than singletons, and this is especially true for monozygotic twins.

Cluster headache: aetiology, diagnosis and management.

Cluster headache is characterised by repeated attacks of strictly unilateral pain in the orbital region associated with local autonomic symptoms or signs. The attacks are brief but of a very severe, almost excruciating intensity. For unknown reasons males are affected more often than females. Recent studies suggest that an autosomal dominant gene has a role in some families with cluster headache. Hormonal studies indicate a dysfunction in the central nervous system. Neuroimaging has revealed primary defects in the hypothalamic grey matter. Local homolateral dilatation in the intracranial segment of the internal carotid and ophthalmic arteries during attacks is the result of a generic neurovascular activation, probably mediated by trigeminal parasympathetic reflexes. Sumatriptan 6mg subcutaneously is the drug of choice in the treatment of acute attacks. Inhalation of 100% oxygen can also be recommended. In the prophylactic treatment, verapamil is the first option. Other drugs that can be considered are corticosteroids, which may induce a remission of frequent, severe attacks, and lithium. Oral ergotamine tartrate may be sufficient for patients with night attacks and/or short, rather mild to moderately severe cluster headache periods. Third line drugs are serotonin inhibitors (methysergide and pizotifen) and valproic acid. Patients should be encouraged to keep headache diaries and be carefully instructed about the nature and treatment of the headaches. Alcohol can bring on extra attacks and should not be consumed during active periods of cluster headache.