Hypoxic-ischaemic brain injury: imaging and neurophysiology abnormalities related to outcome.

BACKGROUND: The outcome for patients with hypoxic-ischaemic brain injury (HIBI) is often poor. It is important to establish an accurate prognosis as soon as possible after the insult to guide management. Clinical assessment is not reliable and ancillary investigations, particularly imaging and EEG, are needed to understand the severity of brain injury and the likely outcome. METHODS: We undertook a retrospective study of 39 patients on an intensive therapy unit (ITU) with HIBI who were referred for MRI. The patients were seen consecutively >57 months. HIBI was due to a variety of insults causing cardiac arrest, hypoperfusion or isolated hypoxia. RESULTS: The outcome was poor, 29 patients died, 7 were left severely disabled and only 3 made a good recovery. Characteristic imaging changes were seen on MRI. These included extensive changes in the cortex and the deep grey matter present on diffusion-weighted imaging (DWI) and T2-weighted imaging within 6 days of the insult. In other patients, different patterns of involvement of the cortex and basal ganglia occurred. There was no significant difference in the outcome or imaging appearances according to aetiology. A poor prognosis was consistently associated with a non- or poorly responsive EEG rhythm and the presence of periodic generalized phenomena with a very low-voltage background activity. CONCLUSION: In this retrospective study of patients with HIBI, MRI and EEG provided valuable information concerning prognosis.

Trends in utilization of antiepileptic drugs in Denmark.

OBJECTIVES: To describe utilization of antiepileptic drugs (AEDs) in Denmark during 1993-2002, with special emphasis on oxcarbazepine, and to assess probable indications for AED use. MATERIALS AND METHODS: We retrieved prescription data from Odense University Pharmacoepidemiological Database, in Funen County, Denmark (population in 2002: 472,869). Within each calendar year we estimated period prevalence, incidence rate and monotherapy rate. Based on co-medication we defined 'epilepsy' when only AEDs were prescribed, 'pain' with co-prescription of opioids, and 'mood disorder' with co-prescription of antipsychotics or antidepressants. RESULTS: We identified 15,604 AED users. The prevalence of using AED increased from 9.3 (95% CI, 9-9.5) to 12.1 (11.8-12.4)/1000 persons. The incidence rate increased from 1.4 (1.3-1.6) to 1.7 (1.6-1.9)/1000 personyears. The monotherapy rate was 79-82%. AED use for 'epilepsy' declined by 19.7%, whereas the proportion of 'pain' and 'mood disorder' treatment increased by 11.2% and 8.4% respectively. CONCLUSIONS: Antiepileptic drug utilization increased during the study period, the increase probably caused by expanding use in areas other than epilepsy.

Long-term effects of migraine on cognitive function: a population-based study of Danish twins.

OBJECTIVE: To investigate the cognitive functioning of migraineurs vs nonmigraineurs in a large population-based sample of middle-aged twins where headache diagnoses were established by neurologists. METHODS: Twins identified through the population-based Danish Twin Registry participated in face-to-face structured interviews, which included cognitive tests and two previously validated questions screening for migraine. Twins who screened positive for migraine and their co-twins were invited to participate in a telephone-based interview conducted by neurologists, who established headache diagnoses according to the International Headache Society criteria. Cognitive scores on fluency, digit span, delayed word recall, and symbol digit substitution test were compared between migraineurs and nonmigraineurs. Comparisons within monozygotic and dizygotic same sex twin pairs discordant for migraine were also performed. RESULTS: Of the 1,789 twins who were eligible for inclusion in the present study, 1,393 (77.8%) were interviewed. A diagnosis of migraine was established in 536 twins (migraine without aura n = 347; migraine with aura n = 157). Average scores on cognitive tests in twins with migraine or one of the migraine subtypes did not differ from those of nonmigraineurs in any of the tests. Comparisons within twin pairs discordant for migraine produced highly comparable results. Adjustment for possible confounders and stratification by cumulated number of lifetime attacks did not influence the results. CONCLUSIONS: A lifetime diagnosis of migraine was not associated with cognitive deficits in middle-aged subjects.

Saliva and serum concentration of lamotrigine in patients with epilepsy.

The authors examined the interindividual correlation between saliva and serum concentrations of lamotrigine (LTG) and the relationship between LTG concentration in saliva and the free LTG concentration in serum in 40 patients with epilepsy, aged 16 to 73 years, receiving stable doses of LTG and comedication. Saliva was collected before and after stimulation of salivary flow. The free LTG fraction was determined by equilibrium dialysis and ultrafiltration. Drug analysis was performed by high-performance liquid chromatography. The correlation between LTG daily dose and serum concentration was weak but significant (r = 0.47). There was high correlation between LTG concentration in serum and unstimulated (r = 0.85) or stimulated (r = 0.94) saliva, and between total LTG concentration in serum and the free LTG fraction as determined by ultrafiltration (r = 0.95) and equilibrium dialysis (r = 0.93). Lamotrigine concentration in stimulated saliva was significantly correlated to the free LTG fraction. Protein binding of LTG calculated from concentration in stimulated saliva, as determined by ultrafiltration and equilibrium dialysis, was 51.8% +/- 13.03%, 68.05% +/- 7.59%, and 58.72% +/- 7.68% (mean +/- standard deviation) respectively. The differences between the three methods were significant. The authors conclude that saliva sampling may be a useful alternative to blood tests for monitoring LTG treatment.

Risk of subarachnoid haemorrhage in first degree relatives of patients with subarachnoid haemorrhage: follow up study based on national registries in Denmark.

OBJECTIVE: To estimate the risk of occurrence of subarachnoid haemorrhage in first degree relatives (parents, siblings, children) of patients with subarachnoid haemorrhage. DESIGN: Population based cohort study using data from the Danish National Discharge Registry and the Central Person Registry. SUBJECTS: Incident cases of subarachnoid haemorrhage admitted to hospital from 1977 to 1995 (9367 patients) and their first degree relatives (14 781). MAIN OUTCOME MEASURES: The incidence rate of subarachnoid haemorrhage was determined for the relatives and compared with that of the entire population, standardised for age, sex, and calendar period. This process was repeated for patients discharged from neurosurgery units, as diagnoses from these wards had high validity (93%). RESULTS: 18 patients had a total of 19 first degree relatives with subarachnoid haemorrhage during the study period, corresponding to a standardised incidence ratio of 2.9 (95% confidence interval 1.9 to 4.6). Patients discharged from neurosurgery wards had a higher standardised incidence ratio (4.5, 2.7 to 7.3). CONCLUSIONS: First degree relatives of patients with subarachnoid haemorrhage have a threefold to fivefold increased risk of subarachnoid haemorrhage compared with the general population.

Mortality and survival in myasthenia gravis: a Danish population based study.

OBJECTIVES: To study mortality and survival of patients with myasthenia gravis. METHODS: 290 patients with myasthenia gravis were studied, including 212 incident cases identified during a comprehensive epidemiological study of myasthenia gravis in western Denmark 1975-89. Follow up was performed on 31 December 1994. Survival curves were constructed using the life table method. Patient data were compared with data from the public Danish population statistics. Death certificates were provided from the National Registry of Death. RESULTS: The annual average crude mortality rate was 1.8 per million (range 1.5-2.2). The myasthenia gravis related mortality rate (myasthenia gravis as underlying or contributory cause) was 1.4 per million (range 1.1-1.8). The age specific mortality rates were low below 50 years. After this age the mortality increased with age in both sexes; after 60 years more rapidly in men than in women. The overall survival rates three, five, 10, and 20 years from diagnosis were 85%, 81%, 69%, and 63% respectively. The survival of both sexes was shorter than that of the corresponding Danish population. Old age at diagnosis, a classification in Osserman-Genkins group IIB or III, and the presence of a thymoma were associated with a less favourable prognosis. The three, five, 10, and 20 year survival rates of thymectomised patients were 94%, 94%, 86%, and 79% respectively. The corresponding figures for the non-thymectomised patients were 78%, 71%, 56%, and 51%. A Cox regression analysis showed that this apparently significant effect of thymectomy was because the thymectomised patients were younger than the non-thymectomised patients. Furthermore, at the time of diagnosis of myasthenia gravis the non-thymectomised patients had a higher frequency of serious conditions associated with myasthenia gravis than the thymectomised patients. CONCLUSION: Patients with myasthenia gravis generally have a relative good prognosis although their survival is shorter than that of the corresponding population. Old age, a classification in Osserman-Genkins group III, and the presence of a thymoma are associated with a less favourable prognosis. In this study, the apparently significant effect of thymectomy was because the thymectomised patients were younger than non-thymectomised patients and because the non-thymctomised patients had a higher frequency of serious conditions associated with myasthenia gravis.

Associated autoimmune diseases in myasthenia gravis. A population-based study.

During a comprehensive epidemiological study of myasthenia gravis (MG) in Western Denmark 1975-1989, we analyzed the occurrence, clinical characteristics and prognosis of associated autoimmune diseases (AAD) in MG patients. AAD were found in 20 of 212 incident cases (9%) and in 30 of 220 prevalent cases (14%). The most common diseases were: thyroid disorders and rheumatic arthritis. Clinically, it was not possible to identify a subgroup of MG patients with a higher risk of AAD. In most MG patients the AAD occurred before thymectomy. The severity of the AAD was not influenced by thymectomy. The remission rate was lower in MG patients with AAD than in MG patients without AAD suggesting that the autoimmune response in MG patients with AAD is more severe.

Incidence and prevalence of myasthenia gravis in western Denmark: 1975 to 1989.

We studied the epidemiology of myasthenia gravis (MG) in western Denmark from 1975 to 1989, basing case identification on records from all hospitals in the survey area. The population surveyed was 2.80 million in 1985. The average annual incidence rate was 5.0 per million population (women, 5.9; men, 4.2). The point-prevalence rate (January 1, 1990) was 78 per million population (women, 102; men, 53). In men, the incidence increased after 40 years. In women, the incidence rates showed a bimodal pattern with a peak of 7.0 in the age group 20 to 29 years and a second peak of 11.7 in the age group 70 to 79 years. The differences in sex- and age-specific incidence rates suggest that younger women are more susceptible to MG than younger men. Old men and postmenopausal women had similar rates. When last examined, 21% of the 220 prevalent cases were in remission and 18% were moderately or severely disabled.

Double-blind placebo-controlled evaluation of flunarizine as adjunct therapy in epilepsy with complex partial seizures.

Flunarizine was compared to placebo in a double-blind cross-over trial of 2 16-week treatment periods separated by a 4-week wash-out period. The patients had epilepsy with complex partial seizures with or without secondary generalised seizures. Twenty-nine patients entered the trial, but 7 dropped out. Of the 22 patients completing the trial, 13 were women; the median was 39 years (range 15-58) and the median duration of epilepsy 23 years (range 4-55). There was no statistically significant difference between flunarizine 15 mg daily and placebo as adjunct therapy in total seizure frequency, neuropsychological tests, and patient's preferences. No interactions with concomitant antiepileptic drugs and no laboratory abnormalities were registered.