Long-term prognosis of ischemic stroke in young adults Hindfelt B, Nilsson 0. Long-term prognosis of ischemic stroke in young adults. Acta Neurol Scand 1992: 86: 440-445. 0 Munksgaard 1992.
I
Prognostic information is provided for 74 young adults (age 16-40 yrs, mean age at stroke 29.5 yrs), who suffered from ischemic stroke and survived the first month after the stroke. The patients were followed for 13-26 yrs; in total for 1190 yrs after their stroke. At follow-up 12 of the patients were dead, mostly from severe underlying disease that was complicated by ischemic stroke. In 3 cases death was unrelated to cerebrovascular disease. Among the surviving 62 patients, 7 had experienced recurrent ischemic events (3 reinfarctions, 4 T1A:s). These 7 patients all had risk factors for cerebrovascular complications already at the time of their primary stroke. It is concluded that the long-term prognosis for ischemic stroke in the young adult is favourable. The recovery from neurological deficits is usually good (exceptions are occlusions within the internal carotid and middle cerebral arteries), the risk for recurrence is low (1.1- 1.2% annualy), and the social prognosis with respect to working capacity and family relation is fair.
Cerebral infarction usually carries a grave prognosis with respect to survival (1,2), persistent morbidity (3,4) and risk for recurrences ($6). Consequently, when a young adult suffers an ischemic stroke, his or her life is at stake. This applies literally as well as in a broader sense - if the individual survives, what are the prospects? What will the future look like? Will the individual be able to adapt to his or her handicap, to maintain family relations, to regain working capacity etc? The questions are many - the definite answers few. In 1976 we published a report on the prognosis of ischemic stroke in young adults (7). The patients had been followed for in average slightly more than four years and our conclusion was that the prognosis was favourable. These results have since been confirmed (8,9). With this study we have extended our original studies (7, 10) by a decade or more, and have included more cases of young adults among our initial series. Material and methods
This series of patients provide long-term prognostic data about ischemic stroke in young adults. Early fatality rate i.e. within one month of the stroke, has earlier been reported (7). Consequently, this series do only give prognostic information for those pa-
440
B. Hindfelt’, 0. Nilsson’
’
Departments of Neurology, Malmo General Hospital, University Hospital of Lund, Sweden
Bengt Hindfelt, Department of Neurology, Malmo General Hospital, Lund University, S-214 01 Malmo, Sweden Accepted for publication March 14, 1992
tients who survived for at least one month after their stroke. Over the period 1965-1978 the included 77 patients (48 men and 29 women, aged 16-40 years; mean 29.5 years) were admitted to the Department of Neurology, University Hospital of Lund. Diagnosis was based on history, clinical examination and laboratory findings (angiography, CT* and CSF findings). A detailed survey of most of this series of patients has earlier been published (7, 10). In the spring 1991 we interviewed almost all the surviving patients included in our previous study, plus another 16 patients (included among the 77 patients). These additional patients were below the age of 40, when they suffered from ischemic stroke over the period 1975-1978. Consequently, we have prognostic information based upon at least 13 years of follow up (range 13-26 years) for no less than 74 young adults with cerebral or brainstem infarction. Among the patients in our original series, 3 could not be contacted. 2 of these were foreigners and could not to be found in social registers. 1 patient, known to be alive, did not respond to our interview request. The additional group (1975-1978) consisted of 18 patients, 2 of whom were dead at the time of follow up. In all cases with subsequent and possibly relevant * CT was
available from 1977.
Young adult ischemic stroke
disorder, their doctor or hospital was contacted for further information. The same was the case for all patients, who had died at the time of follow up. Statistical methods
Fisher’s exact test was used to compare rates in frequency tables. The distribution of lesions between the right and left hemispheres was compared with binomial distribution (p = 0.50) using exact tests.
Anterior circulation Internal carotid artery Bilat. carotid arteries Internal carotid artery and the middle cerebral art. Anterior cerebral artery Middle cerebral artery Uncertain localization Totai: 48
Results
In all, this series of 74 young adults (mean age at the time of the stroke 29.5 yrs, range 16-39 yrs) provide long-term prognostic information for a period of totally 1190 years. At follow-up, 12 (9 men and 3 women) patients were dead. In Table 1-sex, age at stroke (mean 30.5 yrs), time of survival after stroke (mean 7.0 yrs) and the cause of death are presented. The survival times differed markedly; 3 of the patients succumbed from causes unrelated to their ischemic stroke. In summary, most of these patients were severly ill from their underlying disease already at the time of their ischemic stroke. Of the remaining 62 patients still alive, 37 were men and 25 women. Their mean age at the time of stroke was 29.3 yrs (range 16-39 yrs) and these patients have been followed for in total 1100 yrs (mean follow-up 17.7 yrs, range 12-26 yrs). The distribution of the ischemic strokes, as diagnosed by angiography, CT and/or clinical examinaTable 1. Death causes* and suwival times after the initial ischemic stroke. (*Based upon autopsy report or official death certificate)
Sex
Table 2. The locations of vascular pathologies among the 62 still surviving patients as indicated by angiography and/or CT. Exact p values (two-tailed) were calculated from binomial distributions
Age at the inital stroke
Survival time (years)
1. male 2. male
16 29
18 12
3. male 4. male 5. male
39 39 38
21 12 5
6. female
38
2 months
7. male
24
3
8. female 9. male 10. female
23 31 24
2 4 6
11. male
35
6 months
12. male
30
10 months
Cause of death* Intoxication (drugs, alcohol) Cerebral reinfarction thrombotic purpura Dissiminated adenocarcinoma Astrocytoma Cerebral reinfarction, diencephalic astrocytoma, multiple endocrine disturbances, epilepsy Cerebral reinfarction, mitral valve disease Cardiac insufficiency, arterial hypertension, diabetes mellitus Mitral valve disease (operated) Myocardial infarction, diabetes mellitus Uremia Takayashu syndrome Gangrene (op), heart arrythmia/ vegetative state, diabetes mellitus, arterial hypertension, uremia SLE complications
Posterior circulation Posterior cerebral artery Bilat. post. cerebr. art. Sup. cerebellar art. Vertebral art. (PICA) Basilary artery Uncertain localization
Right
Left
1
9 (p=0.34)
0 1 4
3 0 19 (p=0.03) 2
14
33 (p=0.05)
a
7
4
0 3
1 0
Total: 24 Disseminated vascular pathology Anterior/posterior circulation
tion, within different vascular territories, is presented in Table 2. Approximately 2/3 of the patients suffered their infarcts within the anterior circulation, predominantly on the left side (p = 0.05) and within the territory of the middle cerebral artery (p = 0.03). In a minority of patients disseminated vascular pathology was documented. Among the 62 surviving patients, 55 had not experienced any new neurological symptoms since their ischemic stroke; 7 reported that they had suffered from either reinfarctions (3 cases) or episodes of focal neurological dysfunction, compatible with T1A:s (3 cases). In another case of possible TIA, the brief and transient manifestations developed in a manner compatible with an aura of classical migraine. This patient was known to suffer from migraine and had an infarction within the territory of the right posterior cerebral artery. A comparison of the frequencies of risk factors encountered at the time of the primary ischemic stroke, between these 7 patients with recurrent symptoms and those 55 with an uncomplicated course, is presented in Table 3. A risk factor for ischemic stroke was encountered in all the patients subsequently suffering from cerebrovascular complications. Such a factor was only documented in a minority (22%) of the patients with an uncomplicated course . At follow-up 10 patients were on prophylactic treatment with either anticoagulant (n = 5) or ASA (n = 5) therapy. For 3 of these patients the indication 441
Hindfelt & Nilsson Table 3. Various risk factors for cerebrovascular complications encountered among the 62 surviving patients at the time of their primaly ischemic stroke
Number of patients:
Reinfarctions TIAs
Uncomplicated course
7
55
Risk factors: Arterial hypertension Diabetes mellitus Migraine Alcoholism Contraceptive pills
Table 4. Subsequent somatic och psychiatric disorders encountered among the 62 surviving patients during the follow-up period Number of patients Somatic disease Postapoplecticepilepsy Diffuse arthralgia, muscular pain Back pain Arterial hypertension Gastritislulcus Venous thrombosis Endocrine disorders diabetes mellitus thyreotoxicos Claudiocatio intermittens Angina pectoris Myocardial infarction Miscellaneous Persistent headache Migraine Subdural hematoma Vestibular neuronitis GIaucoma Psychiatric disorders Depression Alcoholism, abnormal personality
2
There was just a significant difference in the frequency of epilepsy between the group of dead patients, some of whom suffered from recurrent neurological symptoms, and the group of surviving patients without any recurrences (Fisher's exact test gives a two-sided p = 0.04). A comparison between the frequencies of postapoplectic epilepsy in the group of surviving patients with recurring ischemic events, and the group with an uncomplicated course, did not indicate any significant difference (p = 0.13). The second most common complication, probably or possibly secondary to the stroke, was uncharacteristic pain either manifesting itself as arthralgia, muscular pain or as diffuse back pain (Table 4). Less then 10% subsequently developed arterial hypertension, demanding therapy and, in a similar number of patients, evidence of atherosclerotic vascular disease emerged (Table 4). Major psychiatric disorders were comparably rare (Table4) and only 4 of the still surviving patients manifested overt depressive illnesses, without a preceeding history of similar symptomatology prior to their strokes. In one patient the depression had been associated with psychotic traits. Other psychic ab-
SCORE
30:
'7 3
20
(*3 of these patients had sufferedfrom similar psychiatric illnesses prior to their strokes).
for treatment was recidivating deep venous thrombosis (n = 2) and coronary artery disease (n = 1). The somatic and psychiatric complications that have developed over the post-stroke periods are summarized in table IV. The most frequent late complication was postapoplectic epilepsy, rarely causing therapeutic problems. Postapoplectic epilepsy was observed in 3 of the 12 patients* (25%) who died during the follow-up period, in 2 of the 7 patients (29%) with recurrent neurological manifestations but only in 4 of the 55 (7%) patients with an uncomplicated long-term prognosis.
* The patient, who subsequent developed a right frontal lobe astrocytoma (Table 1, case 4), was omitted as the dtbut of seizures coincided with the diagnosis of brain tumor, several years after the ischemic stroke). 442
Q
1
2
3
Fig. 1. The acute disability score" in comparison with the longterm outcome. 0, 1, 2, 3 denote: no subjective handicap, slight neurological dysfunction, moderate and severe disability, respectively. (The scoring system was not applied to 4 patients with infratentorial lesions).
Young adult ischemic stroke normalities, including alcoholism, were encountered in 3 patients. It is desirable to provide a long-term prognosis, as early as possible after the incurred stroke. Fig. 1 provides some prognostic longterm information. The disability score is based on a previous publication (1 l), to which the reader is referred for details. The score summarizes the deficits in the acute stage i.e. in most cases within the first few days after the stroke, and the long-term outcome, expressed in terms of no, slight, moderate or severe disability. Social prognosis
The short-term prognosis, concerning returning to work, has earlier been reported (7), stating that at least 80% of the young patients will be able to resume work on a full or part-time basis. Among the 62 surviving patients, 39 (63%) reported full working capacity of today (4 patients after retraining). The mean age of these patients was 46.6 years. 7 patients were working part-time, 11because of asbestosis of the lungs; 17 patients had retired (mean age 52.2 years). However, many of these patients, working part-time or being retired, had earlier been able to work full-time even after their strokes (see Discussion). Only 8 of the retired 17 patients had moderate or severe neurological handicaps. Seven patients continuously needed some help from another person for their daily activities. However, in most cases these needs were minor and only 1 patient was cared for at an institution for disabled persons. In 16 families children were born after the stroke. 3 patients were pregnant at the time of their strokes and 5 other women became pregnant after their strokes and had uncomplicated deliveries; 8 patients became fathers after their strokes. Divorce as a consequence of stroke, did occur, but only in one case. Consequently, family complications were very few. Discussion
The present study confirms our previous results indicating, that longterm prognosis of ischemic stroke in young adults is favourable. Thus, the early mortality is low (7), as is the long-term mortality - in this series about 1% /yr. Furthermore, the latter is rather due to progression of the underlying disease, causing cerebrovascular complications, than to cerebrovascular disease as such (Table 1). A substantial group of the patients survived long enough to develope a fatal disease, that was unrelated to their cerebral infarct. The risk for recurrent ischemic events, either as a
brain infarction or as TIA:s, was annually 1.1-1.2% in our complete patient material. Among our surviving 62 patients, the corresponding risk was 0.60.7 % /yr. As the risk for recurrent ischemic stroke in the elderly has been estimated to 5-6%/yr (12, 13), it is evident that the prognosis in the young patient is very favourable. In our early study (7) we also concluded that the recovery from neurological deficits was good. We could do so because recovery is usually almost complete a year or two after the cerebral infarction (14, 15). The impression was strengthened by the results from this follow-up. As shown in Fig. 1, the overwhelming majority of patients had no or minor persistent handicaps. Only 10 of the 62 patients experienced moderate or severe neurological deficits and 8 of these had suffered from occlusions within the internal carotid or middle cerebral arteries (one of the remaining patients had bilateral infarctions within the occipital lobes; another had initially suffered from vertebral/PICA occlusion and had reinfarcted during the follow-up period). Consequently, the worst outcome was seen in patients with occlusions of the internal carotid artery or the proximal part of the middle cerebral artery. The low risk of recurrent ischemic stroke should be mirrored by a low frequency of established risk factors for stroke. This was also the case among our 62 surviving patients, as shown in Table 3. A possibly important risk factor may be migraine (7, 16, 17), a disorder encountered in 8 of the patients. However, the importance of migraine, as a risk factor for cerebrovascular complications, is difficult to assess as it is highly prevalent among young people (18). In this series of young patients, arterial hypertension and diabetes mellitus were infrequent risk factors as opposed to in the elderly (19,20). The potential risk with contraceptive pills is hard to judge from available documentation (2 1, 22), particularly as all the females (n = 5 ) using them were adviced to abandon their use after the stroke. The risk of alcoholism was early emphasized (23), and has been confirmed during recent years (24). The somatic disorders that developed over the postinfarction period (Table 4), do not provide any clues to the pathogenesis of stroke, nor do they indicate any definite risk factors. The most frequent complication was postapoplectic epilepsy, and its occurrence may have some prognostic implications despite that it did never turn up as a therapeutic problem. All patients with this complication, had supratentorial infarcts. The onset varied considerably from weeks to years after the stroke. The implication of these results may be that the risk to developepostapoplectic epilepsyincreases with more devastating cerebral lesions. With one exception (in-
443
Hindfelt & Nilsson farction within the posterior cerebral artery) all patients suffered from occlusions within the internal carotid or the middle cerebral arteries. Among the other somatic disorders/complaints, diffuse or localized pain dominated the panorama (in 11 of 62 patients). Nothing in particular was noticed about the patients’ complaints and, as similar complaints are common among non-stroke individuals, no conclusions can be drawn. Arterial hypertension and diabetes mellitus are both well established risk factors for cerebrovascular complications. However, they are rarely encountered among young adults with acute ischemic stroke (10, 16) and, nor do these diseases emerge to a significant degree even after a prolonged follow-up (Table4). Among the surviving patients 5 of 62 (8%) subsequently developed arterial hypertension, demanding treatment. Only a single patient suffered from newly established diabetes mellitus at followup. Consequently, the spectrum of pathogenetic factors differs from that of the elderly. This fact, combined with the emphasized prognostic differences with respect to risk of recurrence, strongly indicates that the pathophysiology of ischemic stroke in the young is markedly different from that in the elderly. With prolonged follow-up (a period of 12-22 years), as might be expected, a minority of the patients (5/62; 8 %) manifests symptoms of atherosclerotic vascular disease i e angina pectoris, myocardial infarction and claudiocatio intermittens (Table 4). Thus, the relevance of atherosclerosis for stroke in these few patients, may be questioned. Contrary to expectations, major psychiatric complications were few among the interviewed 62 patients. Only 7 (11%) had suffered from significant psychiatric illness (depression) and 3 had periodically suffered from similar symptoms prior to their stroke. Alcholism and abnormal personality were encountered in another 3 patients. This rather low frequency of psychiatric complications probably reflects the generally good outcome of ischemic stroke in young adults. Social prognosis
Our conclusions must be very restricted as a telephone-interview does not necessarily reveal the true facts and possible problems. But certain information should be trusted. The number of patients being retired, working part-time or enjoying full-time work, should not be questioned. In modern society, such matters can easily be checked. Most of our patients (39/62; 63 %) were working full-time, but this figure does not truely reflect the actual working capacity. Thus, a few patients had exhibited full working capacity before they applied for and got pension because of their previ-
444
ous medical history, despite a continuous good working capacity. Consequently, the numbers of employed, full or part-time given in Results, do not reveal the true present state of working capacity. They also reflect social-economic factors, resources for retraining, the labour market, the motivation of the individual, etc. However, when the patients were follow-up within a few years after the stroke, some 80% had resumed full-time work (7), and a decade or more later, still 63% remained in full-time work. These figures provides further evidence that the prognosis of stroke in the young is rather favourable. References 1. SILVERFL, NORRIS JW, LEWISAJ, HACHINSKI VC. Early mortality following stroke:A prospective review. Stroke 1984: 15: 492-496. 2. BONITAR, FORDMA, STEWART AW. Predicting survival after stroke: a three-year follow-up. Stroke 1988: 19: 669673. 3. FEIGENSON JS, MCDOWELL FH, MEESEP, MCCARTHY ML, GREENBERGSD. Factors influencing outcome and length stay in stroke rehabilitation unit. Stroke 1977: 8: 651662. 4. THORNGREN M, WESTLINGB, NORRVING B. Outcome after stroke in patients discharged to independent living. Stroke 1990: 21: 236-240. 5. S ~ c c oRL, WOLFPA, KANNELWB, MCNAMARA PM. Survival and recurrence following stroke. The Framingham study. Stroke 1982: 13: 290-295. 6. FURLANAJ, WHISNANTJP, BAKERHL Jr. Long-term prognosis after carotid artery occlusion. Neurol 1980: 30: 986-988. 7. HINDFELTB, NILSSON 0. The prognosis of ischemic stroke in young adults. Acta Neurol Scand 1977: 55: 123-130. 8. BOGOUSSLAVSKY J, REGLIF. Ischemic stroke in adults younger than 30 years of age. Arch Neurol 1987: 44: 479482. 9. AUF E, SCHNABERTH G , ZEILERK. Langzeitprognose von Patienten mit juvenilem Insult: Katamnestische Ergebnisse. Arch Psychiatr Neurol Sci 1984: 234: 275-280. 10. HINDFELTB, NILSSON 0. Brain infarction in young adults with particular reference to pathogenesis. Acta Neurol Scand 1977: 55: 145-157. 11. HINDFELTB. The prognostic significanceof subfebrility and fever in cerebral infarction. Acta Neurol Scand 1976: 53: 72-79. 12. BAKERRN, SCHWARTZ S, RAMSEYER JC. Prognosis among survivors of ischaemic stroke. Neurology 1968: 18: 933-941. 13. OLSSONJE, MULLERR, BERNELLI S. Long-term anticoagulant therapy for TIA:s and minor strokes with minimum residuum. Stroke 1976: 7: 441-445. 14. ANREWSK, BROCKLEHURST JC, RICHARDS B, LAYCOCK PJ. The rate of recovery from stroke - And its measurement. Int Rehabil Med 1981: 3: 155-161. 15. SKILBECK CE, WADED, LANGTON-HEWER R, WOODV. Recovery after stroke. J Neurol Neurosurg Psychiatr 1983: 46: 5-8. 16. HILTON-JONES D, WARLOW CP. The causes of stroke in the young. J Neurol 1985: 232: 137-143. 17. SACQUEGNA T, ANDREOLI A, BALDRATI A et al. Ischemic stroke in young adults: the relevanceof migrainous infarction. Cephalalgia 1989: 9: 255-258. 18. WATERSWE. Headache (Clin Epidemiol Ser) London: Croom Helm, 1986.
Young adult ischemic stroke 19. WOLFPA, KANNELWB, VERTERJ. Current status of risk factors for stroke. Neurology Clin 1983: 1: 317-343. CH, MCDOWELLF, EASTONJD. Risk factors 20. MILLIKAN in stroke. In: Stroke. Philadelphia: Lea & Febiger, 1987: 7177. F, WIMMER S, DEECKEL. 21. AUFF E, ZEILERK, HOLZNER
Zum Stellenwert der oralen Kontrazeptiva als Risiko-faktor zerebraler Gefasserkrankungen. Wien Klin Wochenschr 1986: 98, pp. 304-310.
22. BRICKJF, RIGGSJE. Ischemic cerebrovascular disease in
the young adult. Emergence of oral contraceptive use and pregnancy as the major risk factors in the 1980s. W V Med J 1989: 85: pp. 7-8. 23. LEE K. Alcoholism and cerebrovascular thrombosis in the young. Acta Neurol Scand 1979: 59: 270-274. M. Ethanol intoxication: a risk factor 24. HILLBOMM, USTE for ischemic infarction in adolescents and young adults. Stroke 1981: 12: 422-425.
445
I
Prognostic information is provided for 74 young adults (age 16-40 yrs, mean age at stroke 29.5 yrs), who suffered from ischemic stroke and survived the first month after the stroke. The patients were followed for 13-26 yrs; in total for 1190 yrs after their stroke. At follow-up 12 of the patients were dead, mostly from severe underlying disease that was complicated by ischemic stroke. In 3 cases death was unrelated to cerebrovascular disease. Among the surviving 62 patients, 7 had experienced recurrent ischemic events (3 reinfarctions, 4 T1A:s). These 7 patients all had risk factors for cerebrovascular complications already at the time of their primary stroke. It is concluded that the long-term prognosis for ischemic stroke in the young adult is favourable. The recovery from neurological deficits is usually good (exceptions are occlusions within the internal carotid and middle cerebral arteries), the risk for recurrence is low (1.1- 1.2% annualy), and the social prognosis with respect to working capacity and family relation is fair.
Cerebral infarction usually carries a grave prognosis with respect to survival (1,2), persistent morbidity (3,4) and risk for recurrences ($6). Consequently, when a young adult suffers an ischemic stroke, his or her life is at stake. This applies literally as well as in a broader sense - if the individual survives, what are the prospects? What will the future look like? Will the individual be able to adapt to his or her handicap, to maintain family relations, to regain working capacity etc? The questions are many - the definite answers few. In 1976 we published a report on the prognosis of ischemic stroke in young adults (7). The patients had been followed for in average slightly more than four years and our conclusion was that the prognosis was favourable. These results have since been confirmed (8,9). With this study we have extended our original studies (7, 10) by a decade or more, and have included more cases of young adults among our initial series. Material and methods
This series of patients provide long-term prognostic data about ischemic stroke in young adults. Early fatality rate i.e. within one month of the stroke, has earlier been reported (7). Consequently, this series do only give prognostic information for those pa-
440
B. Hindfelt’, 0. Nilsson’
’
Departments of Neurology, Malmo General Hospital, University Hospital of Lund, Sweden
Bengt Hindfelt, Department of Neurology, Malmo General Hospital, Lund University, S-214 01 Malmo, Sweden Accepted for publication March 14, 1992
tients who survived for at least one month after their stroke. Over the period 1965-1978 the included 77 patients (48 men and 29 women, aged 16-40 years; mean 29.5 years) were admitted to the Department of Neurology, University Hospital of Lund. Diagnosis was based on history, clinical examination and laboratory findings (angiography, CT* and CSF findings). A detailed survey of most of this series of patients has earlier been published (7, 10). In the spring 1991 we interviewed almost all the surviving patients included in our previous study, plus another 16 patients (included among the 77 patients). These additional patients were below the age of 40, when they suffered from ischemic stroke over the period 1975-1978. Consequently, we have prognostic information based upon at least 13 years of follow up (range 13-26 years) for no less than 74 young adults with cerebral or brainstem infarction. Among the patients in our original series, 3 could not be contacted. 2 of these were foreigners and could not to be found in social registers. 1 patient, known to be alive, did not respond to our interview request. The additional group (1975-1978) consisted of 18 patients, 2 of whom were dead at the time of follow up. In all cases with subsequent and possibly relevant * CT was
available from 1977.
Young adult ischemic stroke
disorder, their doctor or hospital was contacted for further information. The same was the case for all patients, who had died at the time of follow up. Statistical methods
Fisher’s exact test was used to compare rates in frequency tables. The distribution of lesions between the right and left hemispheres was compared with binomial distribution (p = 0.50) using exact tests.
Anterior circulation Internal carotid artery Bilat. carotid arteries Internal carotid artery and the middle cerebral art. Anterior cerebral artery Middle cerebral artery Uncertain localization Totai: 48
Results
In all, this series of 74 young adults (mean age at the time of the stroke 29.5 yrs, range 16-39 yrs) provide long-term prognostic information for a period of totally 1190 years. At follow-up, 12 (9 men and 3 women) patients were dead. In Table 1-sex, age at stroke (mean 30.5 yrs), time of survival after stroke (mean 7.0 yrs) and the cause of death are presented. The survival times differed markedly; 3 of the patients succumbed from causes unrelated to their ischemic stroke. In summary, most of these patients were severly ill from their underlying disease already at the time of their ischemic stroke. Of the remaining 62 patients still alive, 37 were men and 25 women. Their mean age at the time of stroke was 29.3 yrs (range 16-39 yrs) and these patients have been followed for in total 1100 yrs (mean follow-up 17.7 yrs, range 12-26 yrs). The distribution of the ischemic strokes, as diagnosed by angiography, CT and/or clinical examinaTable 1. Death causes* and suwival times after the initial ischemic stroke. (*Based upon autopsy report or official death certificate)
Sex
Table 2. The locations of vascular pathologies among the 62 still surviving patients as indicated by angiography and/or CT. Exact p values (two-tailed) were calculated from binomial distributions
Age at the inital stroke
Survival time (years)
1. male 2. male
16 29
18 12
3. male 4. male 5. male
39 39 38
21 12 5
6. female
38
2 months
7. male
24
3
8. female 9. male 10. female
23 31 24
2 4 6
11. male
35
6 months
12. male
30
10 months
Cause of death* Intoxication (drugs, alcohol) Cerebral reinfarction thrombotic purpura Dissiminated adenocarcinoma Astrocytoma Cerebral reinfarction, diencephalic astrocytoma, multiple endocrine disturbances, epilepsy Cerebral reinfarction, mitral valve disease Cardiac insufficiency, arterial hypertension, diabetes mellitus Mitral valve disease (operated) Myocardial infarction, diabetes mellitus Uremia Takayashu syndrome Gangrene (op), heart arrythmia/ vegetative state, diabetes mellitus, arterial hypertension, uremia SLE complications
Posterior circulation Posterior cerebral artery Bilat. post. cerebr. art. Sup. cerebellar art. Vertebral art. (PICA) Basilary artery Uncertain localization
Right
Left
1
9 (p=0.34)
0 1 4
3 0 19 (p=0.03) 2
14
33 (p=0.05)
a
7
4
0 3
1 0
Total: 24 Disseminated vascular pathology Anterior/posterior circulation
tion, within different vascular territories, is presented in Table 2. Approximately 2/3 of the patients suffered their infarcts within the anterior circulation, predominantly on the left side (p = 0.05) and within the territory of the middle cerebral artery (p = 0.03). In a minority of patients disseminated vascular pathology was documented. Among the 62 surviving patients, 55 had not experienced any new neurological symptoms since their ischemic stroke; 7 reported that they had suffered from either reinfarctions (3 cases) or episodes of focal neurological dysfunction, compatible with T1A:s (3 cases). In another case of possible TIA, the brief and transient manifestations developed in a manner compatible with an aura of classical migraine. This patient was known to suffer from migraine and had an infarction within the territory of the right posterior cerebral artery. A comparison of the frequencies of risk factors encountered at the time of the primary ischemic stroke, between these 7 patients with recurrent symptoms and those 55 with an uncomplicated course, is presented in Table 3. A risk factor for ischemic stroke was encountered in all the patients subsequently suffering from cerebrovascular complications. Such a factor was only documented in a minority (22%) of the patients with an uncomplicated course . At follow-up 10 patients were on prophylactic treatment with either anticoagulant (n = 5) or ASA (n = 5) therapy. For 3 of these patients the indication 441
Hindfelt & Nilsson Table 3. Various risk factors for cerebrovascular complications encountered among the 62 surviving patients at the time of their primaly ischemic stroke
Number of patients:
Reinfarctions TIAs
Uncomplicated course
7
55
Risk factors: Arterial hypertension Diabetes mellitus Migraine Alcoholism Contraceptive pills
Table 4. Subsequent somatic och psychiatric disorders encountered among the 62 surviving patients during the follow-up period Number of patients Somatic disease Postapoplecticepilepsy Diffuse arthralgia, muscular pain Back pain Arterial hypertension Gastritislulcus Venous thrombosis Endocrine disorders diabetes mellitus thyreotoxicos Claudiocatio intermittens Angina pectoris Myocardial infarction Miscellaneous Persistent headache Migraine Subdural hematoma Vestibular neuronitis GIaucoma Psychiatric disorders Depression Alcoholism, abnormal personality
2
There was just a significant difference in the frequency of epilepsy between the group of dead patients, some of whom suffered from recurrent neurological symptoms, and the group of surviving patients without any recurrences (Fisher's exact test gives a two-sided p = 0.04). A comparison between the frequencies of postapoplectic epilepsy in the group of surviving patients with recurring ischemic events, and the group with an uncomplicated course, did not indicate any significant difference (p = 0.13). The second most common complication, probably or possibly secondary to the stroke, was uncharacteristic pain either manifesting itself as arthralgia, muscular pain or as diffuse back pain (Table 4). Less then 10% subsequently developed arterial hypertension, demanding therapy and, in a similar number of patients, evidence of atherosclerotic vascular disease emerged (Table 4). Major psychiatric disorders were comparably rare (Table4) and only 4 of the still surviving patients manifested overt depressive illnesses, without a preceeding history of similar symptomatology prior to their strokes. In one patient the depression had been associated with psychotic traits. Other psychic ab-
SCORE
30:
'7 3
20
(*3 of these patients had sufferedfrom similar psychiatric illnesses prior to their strokes).
for treatment was recidivating deep venous thrombosis (n = 2) and coronary artery disease (n = 1). The somatic and psychiatric complications that have developed over the post-stroke periods are summarized in table IV. The most frequent late complication was postapoplectic epilepsy, rarely causing therapeutic problems. Postapoplectic epilepsy was observed in 3 of the 12 patients* (25%) who died during the follow-up period, in 2 of the 7 patients (29%) with recurrent neurological manifestations but only in 4 of the 55 (7%) patients with an uncomplicated long-term prognosis.
* The patient, who subsequent developed a right frontal lobe astrocytoma (Table 1, case 4), was omitted as the dtbut of seizures coincided with the diagnosis of brain tumor, several years after the ischemic stroke). 442
Q
1
2
3
Fig. 1. The acute disability score" in comparison with the longterm outcome. 0, 1, 2, 3 denote: no subjective handicap, slight neurological dysfunction, moderate and severe disability, respectively. (The scoring system was not applied to 4 patients with infratentorial lesions).
Young adult ischemic stroke normalities, including alcoholism, were encountered in 3 patients. It is desirable to provide a long-term prognosis, as early as possible after the incurred stroke. Fig. 1 provides some prognostic longterm information. The disability score is based on a previous publication (1 l), to which the reader is referred for details. The score summarizes the deficits in the acute stage i.e. in most cases within the first few days after the stroke, and the long-term outcome, expressed in terms of no, slight, moderate or severe disability. Social prognosis
The short-term prognosis, concerning returning to work, has earlier been reported (7), stating that at least 80% of the young patients will be able to resume work on a full or part-time basis. Among the 62 surviving patients, 39 (63%) reported full working capacity of today (4 patients after retraining). The mean age of these patients was 46.6 years. 7 patients were working part-time, 11because of asbestosis of the lungs; 17 patients had retired (mean age 52.2 years). However, many of these patients, working part-time or being retired, had earlier been able to work full-time even after their strokes (see Discussion). Only 8 of the retired 17 patients had moderate or severe neurological handicaps. Seven patients continuously needed some help from another person for their daily activities. However, in most cases these needs were minor and only 1 patient was cared for at an institution for disabled persons. In 16 families children were born after the stroke. 3 patients were pregnant at the time of their strokes and 5 other women became pregnant after their strokes and had uncomplicated deliveries; 8 patients became fathers after their strokes. Divorce as a consequence of stroke, did occur, but only in one case. Consequently, family complications were very few. Discussion
The present study confirms our previous results indicating, that longterm prognosis of ischemic stroke in young adults is favourable. Thus, the early mortality is low (7), as is the long-term mortality - in this series about 1% /yr. Furthermore, the latter is rather due to progression of the underlying disease, causing cerebrovascular complications, than to cerebrovascular disease as such (Table 1). A substantial group of the patients survived long enough to develope a fatal disease, that was unrelated to their cerebral infarct. The risk for recurrent ischemic events, either as a
brain infarction or as TIA:s, was annually 1.1-1.2% in our complete patient material. Among our surviving 62 patients, the corresponding risk was 0.60.7 % /yr. As the risk for recurrent ischemic stroke in the elderly has been estimated to 5-6%/yr (12, 13), it is evident that the prognosis in the young patient is very favourable. In our early study (7) we also concluded that the recovery from neurological deficits was good. We could do so because recovery is usually almost complete a year or two after the cerebral infarction (14, 15). The impression was strengthened by the results from this follow-up. As shown in Fig. 1, the overwhelming majority of patients had no or minor persistent handicaps. Only 10 of the 62 patients experienced moderate or severe neurological deficits and 8 of these had suffered from occlusions within the internal carotid or middle cerebral arteries (one of the remaining patients had bilateral infarctions within the occipital lobes; another had initially suffered from vertebral/PICA occlusion and had reinfarcted during the follow-up period). Consequently, the worst outcome was seen in patients with occlusions of the internal carotid artery or the proximal part of the middle cerebral artery. The low risk of recurrent ischemic stroke should be mirrored by a low frequency of established risk factors for stroke. This was also the case among our 62 surviving patients, as shown in Table 3. A possibly important risk factor may be migraine (7, 16, 17), a disorder encountered in 8 of the patients. However, the importance of migraine, as a risk factor for cerebrovascular complications, is difficult to assess as it is highly prevalent among young people (18). In this series of young patients, arterial hypertension and diabetes mellitus were infrequent risk factors as opposed to in the elderly (19,20). The potential risk with contraceptive pills is hard to judge from available documentation (2 1, 22), particularly as all the females (n = 5 ) using them were adviced to abandon their use after the stroke. The risk of alcoholism was early emphasized (23), and has been confirmed during recent years (24). The somatic disorders that developed over the postinfarction period (Table 4), do not provide any clues to the pathogenesis of stroke, nor do they indicate any definite risk factors. The most frequent complication was postapoplectic epilepsy, and its occurrence may have some prognostic implications despite that it did never turn up as a therapeutic problem. All patients with this complication, had supratentorial infarcts. The onset varied considerably from weeks to years after the stroke. The implication of these results may be that the risk to developepostapoplectic epilepsyincreases with more devastating cerebral lesions. With one exception (in-
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Hindfelt & Nilsson farction within the posterior cerebral artery) all patients suffered from occlusions within the internal carotid or the middle cerebral arteries. Among the other somatic disorders/complaints, diffuse or localized pain dominated the panorama (in 11 of 62 patients). Nothing in particular was noticed about the patients’ complaints and, as similar complaints are common among non-stroke individuals, no conclusions can be drawn. Arterial hypertension and diabetes mellitus are both well established risk factors for cerebrovascular complications. However, they are rarely encountered among young adults with acute ischemic stroke (10, 16) and, nor do these diseases emerge to a significant degree even after a prolonged follow-up (Table4). Among the surviving patients 5 of 62 (8%) subsequently developed arterial hypertension, demanding treatment. Only a single patient suffered from newly established diabetes mellitus at followup. Consequently, the spectrum of pathogenetic factors differs from that of the elderly. This fact, combined with the emphasized prognostic differences with respect to risk of recurrence, strongly indicates that the pathophysiology of ischemic stroke in the young is markedly different from that in the elderly. With prolonged follow-up (a period of 12-22 years), as might be expected, a minority of the patients (5/62; 8 %) manifests symptoms of atherosclerotic vascular disease i e angina pectoris, myocardial infarction and claudiocatio intermittens (Table 4). Thus, the relevance of atherosclerosis for stroke in these few patients, may be questioned. Contrary to expectations, major psychiatric complications were few among the interviewed 62 patients. Only 7 (11%) had suffered from significant psychiatric illness (depression) and 3 had periodically suffered from similar symptoms prior to their stroke. Alcholism and abnormal personality were encountered in another 3 patients. This rather low frequency of psychiatric complications probably reflects the generally good outcome of ischemic stroke in young adults. Social prognosis
Our conclusions must be very restricted as a telephone-interview does not necessarily reveal the true facts and possible problems. But certain information should be trusted. The number of patients being retired, working part-time or enjoying full-time work, should not be questioned. In modern society, such matters can easily be checked. Most of our patients (39/62; 63 %) were working full-time, but this figure does not truely reflect the actual working capacity. Thus, a few patients had exhibited full working capacity before they applied for and got pension because of their previ-
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ous medical history, despite a continuous good working capacity. Consequently, the numbers of employed, full or part-time given in Results, do not reveal the true present state of working capacity. They also reflect social-economic factors, resources for retraining, the labour market, the motivation of the individual, etc. However, when the patients were follow-up within a few years after the stroke, some 80% had resumed full-time work (7), and a decade or more later, still 63% remained in full-time work. These figures provides further evidence that the prognosis of stroke in the young is rather favourable. References 1. SILVERFL, NORRIS JW, LEWISAJ, HACHINSKI VC. Early mortality following stroke:A prospective review. Stroke 1984: 15: 492-496. 2. BONITAR, FORDMA, STEWART AW. Predicting survival after stroke: a three-year follow-up. Stroke 1988: 19: 669673. 3. FEIGENSON JS, MCDOWELL FH, MEESEP, MCCARTHY ML, GREENBERGSD. Factors influencing outcome and length stay in stroke rehabilitation unit. Stroke 1977: 8: 651662. 4. THORNGREN M, WESTLINGB, NORRVING B. Outcome after stroke in patients discharged to independent living. Stroke 1990: 21: 236-240. 5. S ~ c c oRL, WOLFPA, KANNELWB, MCNAMARA PM. Survival and recurrence following stroke. The Framingham study. Stroke 1982: 13: 290-295. 6. FURLANAJ, WHISNANTJP, BAKERHL Jr. Long-term prognosis after carotid artery occlusion. Neurol 1980: 30: 986-988. 7. HINDFELTB, NILSSON 0. The prognosis of ischemic stroke in young adults. Acta Neurol Scand 1977: 55: 123-130. 8. BOGOUSSLAVSKY J, REGLIF. Ischemic stroke in adults younger than 30 years of age. Arch Neurol 1987: 44: 479482. 9. AUF E, SCHNABERTH G , ZEILERK. Langzeitprognose von Patienten mit juvenilem Insult: Katamnestische Ergebnisse. Arch Psychiatr Neurol Sci 1984: 234: 275-280. 10. HINDFELTB, NILSSON 0. Brain infarction in young adults with particular reference to pathogenesis. Acta Neurol Scand 1977: 55: 145-157. 11. HINDFELTB. The prognostic significanceof subfebrility and fever in cerebral infarction. Acta Neurol Scand 1976: 53: 72-79. 12. BAKERRN, SCHWARTZ S, RAMSEYER JC. Prognosis among survivors of ischaemic stroke. Neurology 1968: 18: 933-941. 13. OLSSONJE, MULLERR, BERNELLI S. Long-term anticoagulant therapy for TIA:s and minor strokes with minimum residuum. Stroke 1976: 7: 441-445. 14. ANREWSK, BROCKLEHURST JC, RICHARDS B, LAYCOCK PJ. The rate of recovery from stroke - And its measurement. Int Rehabil Med 1981: 3: 155-161. 15. SKILBECK CE, WADED, LANGTON-HEWER R, WOODV. Recovery after stroke. J Neurol Neurosurg Psychiatr 1983: 46: 5-8. 16. HILTON-JONES D, WARLOW CP. The causes of stroke in the young. J Neurol 1985: 232: 137-143. 17. SACQUEGNA T, ANDREOLI A, BALDRATI A et al. Ischemic stroke in young adults: the relevanceof migrainous infarction. Cephalalgia 1989: 9: 255-258. 18. WATERSWE. Headache (Clin Epidemiol Ser) London: Croom Helm, 1986.
Young adult ischemic stroke 19. WOLFPA, KANNELWB, VERTERJ. Current status of risk factors for stroke. Neurology Clin 1983: 1: 317-343. CH, MCDOWELLF, EASTONJD. Risk factors 20. MILLIKAN in stroke. In: Stroke. Philadelphia: Lea & Febiger, 1987: 7177. F, WIMMER S, DEECKEL. 21. AUFF E, ZEILERK, HOLZNER
Zum Stellenwert der oralen Kontrazeptiva als Risiko-faktor zerebraler Gefasserkrankungen. Wien Klin Wochenschr 1986: 98, pp. 304-310.
22. BRICKJF, RIGGSJE. Ischemic cerebrovascular disease in
the young adult. Emergence of oral contraceptive use and pregnancy as the major risk factors in the 1980s. W V Med J 1989: 85: pp. 7-8. 23. LEE K. Alcoholism and cerebrovascular thrombosis in the young. Acta Neurol Scand 1979: 59: 270-274. M. Ethanol intoxication: a risk factor 24. HILLBOMM, USTE for ischemic infarction in adolescents and young adults. Stroke 1981: 12: 422-425.
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