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Abstract

Migraine patients abusing ergotamine often have chronic daily headaches associated with tiredness, sleep and memory disturbances, and reduced general well‐being. We quantified psychological and cognitive functioning in 12 migraine patients with and 12 without ergotamine abuse (≥ 5 days/week for ≥ 6 months) and 12 healthy controls. Psychological functioning assessed by Symptom Checklist‐90 (SCL‐90) and Profile Of Mood State (POMS), was impaired in ergotamine abusers compared to healthy controls. Cognitive functioning divided into four domains: attention (critical flicker frequency analysis and mental control subscale of the Wechsler Memory Scale (WMS), speed of information processing (reaction time tasks and lexical decision tasks), memory (four subscales of the WMS) and cognitive flexibility (trailmaking test and WMS digits backwards), was impaired in ergotamine abusers in speed of information processing and cognitive flexibility. These differences disappeared after correction for total SCL‐90 scores. In conclusion, ergotamine abuse is associated with high psychological distress but not with structural impaired cognitive functioning.

Keywords

Ergotamine abuse ergot headache psychological distress cognitive functioning withdrawal

Despite formal lack of evidence for efficacy and a wide range of often severe side‐effects, ergots are still being frequently used in the treatment of migraine attacks (1). On long‐term use, many patients will develop the syndrome of ‘ergot headache’, characterized by gradual increase of headache frequency and ergot consumption (2, 3). Ultimately, patients will use ergots (nearly) daily and will have chronic (nearly) daily headache associated with tiredness, attention problems, sleep and memory disturbances, and reduced general well‐being (4–6). These symptoms usually improve after drug withdrawal (7–9). Little is known about the effects of ergotamine abuse on psychological and cognitive functioning. Three studies, one using critical flicker fusion analysis (10) and two using visual evoked potentials (11, 12) have suggested impaired cognitive functioning in patients with ’ergot headache’. The present study was designed to quantify differences in psychological distress and cognitive performance in migraine patients with and without ergotamine abuse.

Methods

Subjects

Ergotamine‐abusing patients were recruited through advertisement in newspapers and the journal of the Dutch migraine patient association. Ergotamine abuse was defined as intake of ergotamine‐containing medication on 5 or more days a week, for more than 6 consecutive months. For each ergotamine abuser an age‐ and sex‐matched migraine patient (13) was selected from the migraine patient database of the neurology outpatient clinic of Leiden University Medical Centre. They were not to use or to have ever used on a regular basis ergotamine‐containing drugs on more than 1 day per 2 weeks. Age‐ and sex‐matched friends of the patients who had never experienced a migraine attack, nor had suffered from tension‐type headaches for more than 10 days a month or had abused analgesics, were invited as second control group. Approval of the study protocol was obtained from the local ethics committee of Leiden University Medical Center and informed consent was obtained from each subject before enrolment in the study.

Study design

All participants were investigated using a standardized protocol. Subjects were asked to complete a headache and medication questionnaire and the Symptom Checklist‐90 (SCL‐90) at home. During a visit to the hospital all participants were asked about their education years and level. Education years were defined as the amount of education years after primary school. Education level was defined using a 5‐point scale in which 1 represents special education, 2 = lower, 3 = middle, 4 = higher secondary school and 5 = university. Thereafter, short physical and neurological examinations were performed and participants were asked to complete the shortened Profile of Mood State (POMS) and to perform several neuropsychological tests. Ergotamine abusers were asked to withdraw abruptly from ergotamine. Those who did so were retested at least 3 months after withdrawal.

Psychological distress measures

The SCL‐90 estimates the general psychological and somatic state of the participants, and consists of 90 statements, which have to be rated on a 5‐point scale (14–15). The questionnaire shows a high validity and has been used previously in substance abuse populations (16–18). The Dutch version comprises nine subscales: depression, somatization, interpersonal sensitivity, obsessive‐compulsive disorder, anxiety, hostility, phobic anxiety, sleeping problems and miscellaneous. The total SCL‐90 score indicates the general level of distress. The questionnaire was completed by all participants in their usual environment, on a normal weekday and reflected the psychological distress over the past 7 days. The POMS measures the actual psychological state of the participant and consists of 32 feelings, which have to be rated on a 5‐point scale (19–20). It comprised five subscales: depression, anger, fatigue, tension and vigour. All items of the POMS referred to the patient's feeling at the time of completing the questionnaire (during the hospital visit).

Cognition

Based on complaints from ergotamine abusers, like tiredness, concentration problems, sleep and memory disturbance and reduced general well‐being, we selected four different neuropsychological domains in which we expected to see differences between the three groups. The selected domains, earlier described by Denburg et al. (21), were attention, speed of information processing, memory and cognitive flexibility. For each of the four domains standard neuropsychological measurements were used.

Attention was measured by the critical flicker fusion test (CFF) (10–22) and the mental control subscale of the Wechsler Memory Scale (WMS) (23).

Speed of information processing was measured by simple and complex visual reaction time tasks (24) and the lexical decision task (LEXDEC). The LEXDEC is a four‐level test with increasing cognitive task load (25), during which subjects had to evaluate words which appeared on a PC screen by pressing keyboard keys (← ‘yes’ or → ‘no’) according to the following criteria: onset of appearance (test 1, 25 trails for each key), written in capitals or not (test 2, 50 trials), representing organic matter or not (test 3), and finally, written in non‐capitals and representing non‐organic matter or not (test 4). For each task condition the same set of words was used, and reaction times and accuracy (% correct reactions) were computed.

Memory was assessed with four subscales of the WMS: immediate verbal memory (digits forward), verbal memory (logical passages), visual‐spatial memory (visual reproduction) and verbal learning (paired association) (23).

Cognitive flexibility was measured by trailmaking test A and B (22–27) and WMS digits backwards (23).

Statistical analysis

Differences between groups were analysed by means of the Kruskal–Wallis one‐way anova. Post hoc pair‐wise group analysis was performed with the Mann–Whitney U‐test. P‐values < 0.005 were considered statistically significant and 0.005 < P < 0.05 borderline significant. When differences between the three groups were found, trend analyses were performed to test for linear relationships in the order ergotamine abusers, migraine patients and healthy controls (P < 0.05 was considered statistically significant). When the Kruskal–Wallis one‐way anova showed differences in cognitive performances these differences were corrected for influence of psychological distress by analysis of covariance (ancova) with total SCL‐90 score as covariate (P < 0.05). All data in the text and figures are presented as mean ± sem.

Results

Subjects

The demographic and clinical characteristics of the study population are summarized in Table 1. A total of 12 ergotamine abusers (years of addiction 11.3 ± 2.3) entered the study. The average number of days of ergotamine intake per month was 28 ± 1, and the average dose per day was 2.1 ± 0.3 mg. One patient used in addition daily sumatriptan, six patients used daily analgesics, two used antidepressive medication, one used benzodiazepines, and three used β‐blockers (two as prophylactic medication for migraine and one for hypertension). All abusers took their normal daily dose of ergotamine on the day of investigation. Two migraine patients used β‐blockers (one for prophylactic medication and one for hypertension). The three groups showed no differences in education years or level of education.

TABLE 1

Demographic and clinical characteristics of study population (n = 36)

	Ergotamine abusers (n = 12)	Migraine patients (n = 12)	Healthy controls (n = 12)
Gender (female)	11	11	11
Age (years)∗	56 ± 2	56 ± 2	55 ± 3
Education years∗	5 ± 1	6 ± 1	7 ± 1
Education level∗	4 ± 1	3 ± 1	3 ± 1
Migraine history
Migraine with aura	0	0	–
Migraine without aura	10 (83%)	10 (83%)	–
Both	2 (17%)	2 (17%)	–
Age of onset (years)∗	23 ± 3	20 ± 2	–
Number of attacks/month∗	29 ± 1	4 ± 1	–
Sumatriptan use	3 (25%)	9 (75%)	–
Prophylactic treatment	2 (17%)	2 (17%)	–
Analgesics use	8 (66%)	6 (50%)	3 (25%)
days/month∗	12 ± 4	4 ± 1	< 1

∗

Expressed as mean ± sem.

Psychological distress

Total SCL‐90 scores (the general level of distress) differed significantly between the three groups (ergotamine abusers: 157 ± 13, migraine patients: 122 ± 7, healthy controls: 102 ± 2, P < 0.005). These differences were primarily due to differences between ergotamine abusers and healthy controls (P < 0.0001). Trend analysis showed a significant linear decline in total SCL‐90 score from ergotamine abusers to healthy controls (P trend = 0.0001). SCL‐90 subscale scores are shown in Fig. 1. None of the POMS subscales differed significantly between the three groups (Fig. 2). Four of the five subscales showed a linear decline from ergotamine abusers to healthy controls.

Figure 1

The SCL‐90 subscale scores expressed as mean ± sem. Interpretation of scores: a high score indicates high psychological distress (low well‐being). DEP = depression, SOM = somatization, INT = interpersonal sensitivity, OBS = obsessive‐compulsive disorder, ANX = anxiety, HOS = hostility, PHO = phobic anxiety, SLE = sleeping problems. ∗∗Significant difference between the three groups (P < 0.005). ∗Borderline significant difference between the three groups (0.005 < P < 0.05). ¹Significant difference between ergotamine abusers vs. healthy controls (P < 0.0001 to P = 0.003) for the DEP, SOM, INT, OBS and ANX subscales. ²Significant difference between ergotamine abusers vs. migraine patients (P = 0.003) for the SOM subscale. For all subscales: trend analysis showed a significant linear decline in scores from ergotamine abusers to healthy volunteers (P trend < 0.0001 to P = 0.04). •= ergot; ▴ = migraine; ♦= controls.

Figure 2

The POMS subscale scores expressed as mean ± sem. Interpretation of scores: high depression (DEP), fatigue (FAT), tension (TEN) and anger (ANG) scores and low vigour (VIG) scores indicate high psychological distress. For DEP, FAT, TEN and VIG subscales: trend analysis showed a significant linear relationship (P trend = 0.005 to P = 0.03). • = ergot; ▴ = migraine; ♦ = controls.

Cognition

All measures of cognition are summarized in Table 2. The measurements for attention and memory did not differ between the three groups. Speed of information processing differed significantly between groups only for complex reaction time tasks (CRT; P = 0.02). The total CRT tended to be longer in the ergotamine abusers compared to both migraine patients (mean difference: 0.11 ± 0.03 s, P = 0.008) and healthy volunteers (mean difference: 0.09 ± 0.04 s, P = 0.03). This difference was due to a significantly longer motor time compared to healthy controls and borderline significant longer motor time compared to migraine patients (Table 2). The accuracy, measured as percentage correct reaction, did not differ significantly during the reaction time tests and the LEXDEC tests (data not shown). The cognitive flexibility measurements differed significantly between groups for speed of trailmaking test A, and tended to be different for speed of Trailmaking test B (Table 2).

TABLE 2

Results of cognitive measurements for the four neuropsychological domains (mean ± sem)

	Ergotamine abusers (n = 12)	Migraine patients (n = 12)	Healthy controls (n = 12)
Attention
CFF (Hz)	38.5 ± 0.8	39.0 ± 0.6	38.8 ± 0.6
WMS mental control	7.5 ± 0.5	8.1 ± 0.3	7.5 ± 0.3
Speed of information processing
Simple reaction time (s)
Decision time	0.31 ± 0.02	0.28 ± 0.02	0.31 ± 0.02
Motor time	0.23 ± 0.02	0.19 ± 0.01	0.19 ± 0.01
Complex reaction time (s)
Decision time	0.44 ± 0.02	0.40 ± 0.01	0.43 ± 0.03
Motor time	0.25 ± 0.02	0.19 ± 0.01	0.18 ± 0.01∗∗ †
Lexdec (s)
Test I	0.49 ± 0.04	0.42 ± 0.02	0.43 ± 0.03
Test II	0.83 ± 0.06	0.73 ± 0.05	0.72 ± 0.05
Test III	0.91 ± 0.05	0.83 ± 0.03	0.81 ± 0.03∗
Test IV	1.32 ± 0.12	1.13 ± 0.08	1.17 ± 0.10
Memory WMS
Digits forward	6.5 ± 0.3	6.0 ± 0.3	5.8 ± 0.3
Logical passage	7.0 ± 0.8	9.8 ± 0.8	8.8 ± 0.6†
Visual reproduction	10.0 ± 0.6	11.3 ± 0.6	10.4 ± 0.7
Paired associates	15.6 ± 1.0	18.4 ± 0.8	16.8 ± 0.7† ‡
Cognitive flexibility
Trailmaking test A (s)	53 ± 4	42 ± 3	35 ± 2∗∗
Trailmaking test B (s)	95 ± 7	85 ± 7	75 ± 7∗
WMS digits backwards	4.4 ± 1.2	4.7 ± 0.3	4.7 ± 0.3

∗∗

P < 0.005;

∗

P < 0.05 ergotamine abusers vs. healthy controls.

†

P < 0.05 ergotamine abusers vs. migraine patients.

‡

P < 0.05 migraine patients vs. healthy volunteers.

Since psychological distress influences cognitive performances (28), we corrected the found differences in motor time (CRT) and speed of trailmaking test A for total SCL‐90 scores. After correction, neither of the two tests differed significantly between the three groups (P = 0.88, P = 0.14, respectively).

Withdrawal

Seven patients withdrew from ergotamine within the study period. Compared to those who did not they tended to have more years of education (6 ± 1 vs. 3 ± 1 years, respectively; P = 0.02) and lower SCL‐90 depression scores (23 ± 3 vs. 37 ± 5, respectively; P = 0.04). Stopping was not related to years of addiction, dosage of ergotamine used or any of the cognitive performances. During the first weeks after withdrawal patients experienced severe headaches (7/7), nausea (6/7), vomiting (6/7), sleep disturbances (2/7), perspiration (2/7) palpitations (2/7) and tiredness (2/7). The duration of these withdrawal symptoms was 26 ± 7 days. Table 3 shows individual changes after withdrawal for the SCL‐90 scores (Fig. 3) and the two cognitive performances CRT and trailmaking test A. Compared to non‐responders patients who responded to withdrawal therapy (reduction of more than 20 headache days per month) showed lower SCL‐90 scores and were faster in the trailmaking test A and CRT during the second measurement.

Figure 3

Total SCL‐90 scores of seven ergotamine abusers before and after withdrawal (mean withdrawal period 5.4 ± 1.8 months). The numbers of headache days per month before and after withdrawal are indicated.

TABLE 3

Individual differences in psychological distress and cognitive performances after ergotamine withdrawal

PatientsNR/age	Withdrawal(months)	Number of headache days∗	SCL‐90(total score)	TMT‐A(s)	CRT‐MT (s)
PatientsNR/age	Withdrawal(months)	Before	SCL‐90(total score)	TMT‐A(s)	CRT‐MT (s)	After
1/63	4.5	30	25	30	22	0.04
2/55	6	30	25	0	2	− 0.19
3/57	3	30	19	3	39	0.15
4/45	9	30	9	− 62	− 26	− 0.24
5/54	6	30	4	− 34	1	− 0.03
6/62	5	30	6	– 21	− 17	− 0.10
7/54	4	30	4	– 2	− 29	− 0.06
Mean	5.5	30	13	– 12	− 1	− 0.06

Age in years; TMT‐A = trailmaking test A; CRT‐MT = motor time during the complex reaction time task.

∗

Number of headache days per month before and after withdrawal; reduction of more than 20 headache days after withdrawal was defined as response to withdrawal treatment.

Discussion

In this study we objectivated psychological and cognitive functioning of migraine patients abusing ergotamine by means of a neuropsychological test battery. We found that ergotamine abusers showed higher psychological distress (total SCL‐90 scores) compared to healthy controls, and that migraine patients had intermediate scores (Fig. 1). Furthermore, we found that for the four selected cognitive domains ergotamine abusers had a slower speed of information processing (complex reaction time) and lower cortical flexibility (trailmaking test) compared to healthy controls. Again, migraine patients scored in‐between. However, the three groups did not differ in cognitive functioning after correction for psychological distress (total SCL‐90 score). Thus, ergotamine abusers and to a lesser degree migraine patients performed worse on two cognitive tests than healthy controls, most likely due to higher psychological distress.

This correlation between psychological and cognitive functioning is supported by findings in the seven abusers who were tested at least 3 months after withdrawal from ergotamine. All patients who improved after withdrawal (≤ 10 headache days per month) showed decreased psychological distress and performed better on the two cognitive tests (Table 3). Although both other groups were not tested for the second time, it seems unlikely that learning effects influenced our findings, since three patients with more than 15 headache days left after withdrawal performed worse on both psychological as well as cognitive functioning. Thus, response to withdrawal therapy is associated with reduction in psychological distress and improved cognitive functioning.

Psychological distress

The present findings show that ergotamine abusers scored high on the total SCL‐90 scale and most of the subscales. The high scores on the somatization subscale suggest a high level of physical symptoms, whereas high scores on the depression and anxiety subscales suggest large psychological problems in everyday life. Migraine patients scored in‐between ergotamine abusers and healthy controls. This is in agreement with earlier findings with other questionnaires in which migraine patients showed increased occurrence of depression (29–30), perceived disturbed contentment and vitality (MSEP (31)), more emotional distress (SSAP (31)) as well as a lesser sense of well‐being (PGWB (31); MOS (32); SF‐36 (33–35)) than did healthy control persons. When frequency of migraine attacks is used as measure for disease severity (35), ‘ergotamine’ headache (daily migraine‐like headache) can be seen as a very severe form of migraine with high psychological distress and low general well‐being.

Cognition

We could not objectivate impairment of cognitive functioning in ergotamine abusers. In contrast with this finding are the results of MRI investigations in the same participants during the same visit. All MRIs were scored for white matter hyperintensities (WMH; for detailed information see Bakker et al. 1999). Normal white matter (no lesion or only a single one) was found in none of the ergotamine abusers (0%; 95% C.I. = 0–26%), in four of the 12 migraine patients (33%; 95% C.I. = 9–65%) and in seven of the 12 healthy volunteers (58%; 95% C.I. = 28–65%). The mean number of WMH differed significantly between ergotamine abusers and healthy controls (P = 0.007). Since other risk factors for WMH were excluded, and groups were matched for age and sex, these data suggest that ergotamine abuse is related to structural damage in the white matter of the brain.

Earlier investigations in different populations suggest that WMH are related to cognitive decline (36–40). We found no correlation between cognitive functioning and severity of WMH. This lack of correlation can be explained by two factors. Firstly, earlier investigations were mostly done in subjects with hypertension or other cerebrovascular diseases instead of healthy controls. Most studies in healthy volunteers failed to find a relationship between WMH and cognitive performance (39–43). Some studies, however, found this relationship in the assessment of speed of information processing and cognitive flexibility (38–46). Secondly, none of these earlier investigations corrected cognitive performance for psychological distress. We concluded that white matter lesions in ergotamine abusers were not associated with general cognitive decline at the time of investigation.

In conclusion, ergotamine abuse in migraine patients is associated with high psychological distress but not with structural impaired cognitive functioning. Migraine patients scored in‐between ergotamine abusers and healthy volunteers. After withdrawal, psychological and cognitive functioning improved, proportional to reduction in headache frequency.

Footnotes

Acknowledgements

This study was in part financially supported by Glaxo‐Wellcome B.V., The Netherlands.

References

1 Ferrari

. Migraine. Lancet 1998; 351: 1043–51.

2 Meyler

. Side effects of ergotamine. Cephalalgia 1996; 16: 5–10.

3 Saper

. Ergotamine dependency – a review. Headache 1987; 27: 435–8.

4 Rapoport

Weeks

. Characteristics and treatment of analgesic rebound headache. In: Diener

Wilkinson

, eds. Drug‐Induced Headache. Berlin: Springer‐Verlag, 1988: 162–7.

5 Elkind

. Drug abuse and headache. Med Clinics North Am 1991; 75: 717–32.

6 Mathew

Kurman

Perez

. Drug induced refractory headache‐clinical features and management. Headache 1990; 30: 634–8.

7 Williams

ACC

Richardson

Nicholas

et al.Inpatient vs. outpatient pain management: results of a randomized controlled trial. Pain 1996; 66: 13–22.

8 Hering

Steiner

. Abrupt outpatient withdrawal of medication in analgesic‐abusing migraineurs. Lancet 1991; 337: 1442–3.

9 Mathew

. Management of ergotamine withdrawal. In: Diener

Wilkinson

, eds. Drug‐Induced Headache. Berlin: Springer‐Verlag, 1988: 150–6.

10.

10 Schnider

Maly

Mraz

et al.MMPI and critical flicker frequency (CFF) analysis in headache patients with and without drug abuse. Headache 1995; 35: 17–20.

11.

11 Grotemeyer

Husstedt

Settelmayer

et al.Optically‐elected event‐related potentials and reaction time in healthy persons, migraine patients without ergotamine, and those under ergotamine therapy. In: Clifford Rose

, ed. New Advances in Headache Research. London: Smith‐Gordon, 1994: 61–4.

12.

12 Evers

Schmidt

Bauer

et al.The impact of ergotamine‐induced headache and ergotamine withdrawal on information processing. Psychopharmacology 1999; 142: 61–7.

13.

13 Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgia's, and facial pain. Cephalalgia 1988; 8 (Suppl. 7):1–96.

14.

14 Arrindell

Ettema

. SCL‐90; Handleiding Bij Een Multidimensionele Psychopathologie‐Indicator. Lisse: Swets and Zeitlinger, 1986.

15.

15 Derogatis

Cleary

. Factorial invariance across gender for the primary symptom dimension of SCL‐90. Br J Soc Clin Psychol 1977; 16: 347–56.

16.

16 Haver

. Screening for psychiatric comorbidity among female alcoholics: the use of a questionnaire (SCL‐90) among woman early in their treatment program. Alcohol Alcoholism 1997; 32: 725–30.

17.

17 Holi

Sammallahti

Aalberg

VAA

. Finnish validation study of the SCL‐90. Acta Psychiatr Scand 1998; 97: 42–6.

18.

18 Zack

Toneatto

. The SCL‐90 factor structure in comorbid substance abusers. J Substance Abuse 1998; 10: 85–101.

19.

19 Wald

FDM

Mellenberg

. De verkorte versie van de Nederlandse vertaling van de Profile of Mood States (POMS). Nederlands Tijdschrift Voor Psychologie 1991; 45: 86–90.

20.

20 McNair

Lorr

Droppleman

. Manual for the Profile of Mood States. San Diego, California: Educational and Industrial Testing Service, 1981.

21.

21 Denburg

Carbotte

Denburg

. Cognitive impairment in systemic lupus erythematosus: a neuropsychological study of individual and group deficit. J Clin Exp Neuropsychol 1987; 9: 323–39.

22.

22 Speen

Strauss

. Compendium of Neuropsychological Tests, 2nd edn. Oxford: Oxford University Press, 1998.

23.

23 Wechsler

. The Wechsler Memory Scale. Form 1. New York: The Psychological Corporation, 1945.

24.

24 Middelkoop

HAM

Vink

Lanser

JBK

. Movement initiation and execution times in the study of human cognition and motor performance: differential and significant effects of sex and age. In: Beersma

DGM

, ed. Sleep‐Wake Research in the Netherlands, 7th edn. Utrecht: Elinkwijk, 1996: 107–10.

25.

25 Mahurin

Pirozzolo

. Application of Hick's law of response speed in Alzheimer and Parkinson's disease. Perceptual Motor Skills 1993; 77: 107–13.

26.

26 Armitage

. An analysis of certain psychological tests used for the evaluation of brain injury. Psychol Monogr 1946; 60: 1–48.

27.

27 Reitan

. Validity of the trail‐making test as an indicator of organic brain damage. Perceptual Motor Skills 1958; 8: 271–6.

28.

28 Dufouil

Fuhrer

Dartigues

Alperovitch

. Longitudinal analysis of the association between depressive symptomatology and cognitive deterioration. Am J Epidemiol 1996; 144: 634–41.

29.

29 Keck

Jr Merikangas

McElroy

Strakowski

. Diagnostic and treatment implications of psychiatric comorbidity with migraine [Review]. Ann Clin Psychiatry 1994; 6: 165–71.

30.

30 Breslau

Davis

. Migraine, physical health and psychiatric disorder: a prospective epidemiologic study in young adults. J Psychiatr Res 1993; 27: 211–21.

31.

31 Dahlof

CGH

Dimenas

. Migraine patients experience poorer subjective well‐being/quality of life even between attacks. Cephalalgia 1995; 15: 31–6.

32.

32 Solomon

Skobieranda

Gragg

. Quality of life and well‐being of headache patients: measurement by the Medical Outcomes Study Instrument. Headache 1993; 33: 351–8.

33.

33 Essink‐bot

van Royen

Krabbe

Bonsel

Rutten

FFH

. The impact of migraine on health status. Headache 1995; 35: 200–6.

34.

34 Osterhaus

Townsend

Gandek

Ware

. Measuring the functional status and well‐being of patients with migraine headache. Headache 1994; 34: 337–43.

35.

35 Terwindt

Ferrari

Tijhuis

et al. The impact of migraine on quality of life: a population based study. submitted, 1999.

36.

36 Mirsen

Lee

Wong

et al.Clinical correlates of white‐matter changes on magnetic resonance imaging of the brain. Arch Neurol 1991; 48: 1015–20.

37.

37 Longstreth

Manolio

Arnold

. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The cardiovascular health study. Stroke 1996; 27: 1274–82.

38.

38 Schmidt

Fazekas

Koch

et al.Magnetic resonance imaging, cerebral abnormalities and neuropsychologic test performance in elderly hypertensive subjects. A case‐control study. Arch Neurol 1995; 52: 905–10.

39.

39 Almkvist

Wahlund

Andersson‐lundman

Basun

Bäckman

. White‐matter hyperintensity and neuropsychological functions in dementia and healthy aging. Arch Neurol 1992; 49: 626–32.

40.

40 van Swieten

Geyskes

Derix

MMA

et al.Hypertension in the elderly is associated with white matter lesions and cognitive decline. Ann Neurol 1991; 30: 825–30.

41.

41 van Swieten

Staal

Kappelle

Derix

MMA

van Gijn

. Are white matter lesions directly associated with cognitive impairment in patients with lacunar infarcts? J Neurol 1996; 234: 196–200.

42.

42 Tupler

Coffey

Logue

Djang

Fagan

. Neuropsychological importance of subcortical white matter hyperintensities. Arch Neurol 1992; 49: 1248–52.

43.

43 Fein

Van Dyke

Davenport

et al.Preservation of normal cognitive functioning in elderly subjects with extensive white‐matter lesions of long duration. Arch Gen Psychiatry 1990; 47: 220–3.

44.

44 DeCarli

Murphy

DGM

Tranh

et al.The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 adults. Neurology 1995; 45: 2077–84.

45.

45 Fukui

Sugita

Takeuchi

Tsukagoshi

. Cognitive functions in subjects with incidental cerebral hyperintensities. Eur Neurol 1994; 34: 272–6.

46.

46 Ylikoski

Ylikoski

Erkinjuntti

et al.White matter changes in healthy elderly persons correlate with attention and speed of mental processing. Arch Neurol 1993; 50: 818–24.

The Influence of Ergotamine Abuse on Psychological and Cognitive Functioning

Abstract

Keywords

Methods

Subjects

Study design

Psychological distress measures

Cognition

Statistical analysis

Results

Subjects

Psychological distress

Cognition

Withdrawal

Discussion

Psychological distress

Cognition

Footnotes

Acknowledgements

References