=Acta Neurochirurgica
Acta Neurochir (Wien) (1992) 119:29-34
9 Springer-Verlag 1992 Printed in Austria
Subarachnoid Haemorrhage of Unknown Aetiology A~ Ronkainen and J. Hernesniemi Department of Neurosurgery, University Hospital of Kuopio, Kuopio, Finland
Summary Eighty-six of 996 patients with primary subarachnoid haemorrhage (SAH) had negative panangiography studies. These 86 patients with subarachnoid haemorrhage of unknown origin (SAHNUD) were compared with 853 patients sustaining an aneurysmal bleed (SAH-A) admitted during the same period 1980- 1989. The age and sex distribution of both groups were similar. The SAHNUD group was in better condition on admission, with less blood evident on CT scan. All 16 (repeat control) angiography studies in the SAH-NUD group were negative. During a follow-up period ranging from 1 to 10 years (mean 5.4 years), two patients experienced rebleeding with negative repeat angiographies and subsequent total recovery. Using the Glasgow Outcome Scale (GOS) the final outcome
was good in 86% of the study group and 54% of the aneurysm group. However, half of the SAH-NUD patients complained of persistent symptoms at long-term follow-up. Thus, despite a generally good prognosis, for a given individual SAH-NUD may be catastrophic with many residual symptoms persisting for the rest of the person's life. Keywords: Subarachnoid haemorrhage; negative panangiography; unknown aetiology.
Introduction N o w a d a y s i n m o r e t h a n 4/5 & p a t i e n t s w i t h p r i m a r y subarachnoid haemorrhage (SAH) the bleeding point
Table 1. Aetiology o f Non-Traumatic S A H
Year
SAH
Aneurysm
AVM
Total
No.
%
No.
104l 140 113 94 849 308 529 369 469 1322 1180 814 50 120 996
901 80 84 68 760 256 339 288 424 1192 815 763 42 92 853
87% 57% 74% 72% 90% 83% 64% 78% 90% 90% 69 % 94% 84% 77% 86%
- - * 22 6 3 - - ** 8 40 23 - - * 58 104 5 - -* - -* 57
8394
6957
83%
326
SAH-NUD %
No.
%
no,
Aleksander etal. Andrioli etal. Bj6rkesten etal. Bonita et al. Cioffi et al. Eskesen et al. Forster et al. Giombini etal. Iwanaga et al. Kawamura etal. Shephard Suzuki et al. Van Gijn etal. Van Gijn etal. Present study
1986 1979 1964 1985 1989 1984 1978 1988 1990 1990 1984 1987 1980 1985 1990
Total: - - * Excluded from the study. - - ** Statistics are missing.
6%
140 38 17 23 65 44 150 58 37 72 261 41 8 28 86
13% 27% I5% 24% 8% I4% 28% 16% 8% 5% 22 % 5% 16% 23% 9%
6%
1068
13%
16% 5% 3% 3% 8% 6% 4% 9% 0.6%
30
A. Ronkainen and J. Hernesniemi: Subarachnoid Haemorrhage of Unknown Aetiology
can be demonstrated either by CT scan, cerebral angiography or M R I study (Table 1) 1' 2, 4, 16, 19, 43. In the days when angiography was the only neuroradiological method available, the group of patients with subarachnoid haemorrhage of unknown aetiology (SAH-NUD) was heterogeneous and formed a high percentage (up to 46 per cent) of patients with SAH 24. Cases of spontaneous intracerebral haematomas, tumours, cerebral contusions and undiagnosed aneurysms (especially in the posterior circulation, as many series included patients without vertebral angiograms) were included in even the most sophisticated series. Nowadays with CT scans S A H - N U D seems to be a well-defined group. This subgroup of SAH has a good prognosis without any specific treatment I' 5, 29, 34, 35, 39 and rebleeding occurs very s e l d o m 2' 14, 19, 23, 24 For unknown reasons the incidence of SAH in Finland is one of the highest in the world ~I' 31. We have evaluated the natural history of SAH-NUD, correlated clinical and CT findings with those of SAH-A and followed up the patients carefully to determine the final outcome of the disease. Patients and Methods
nimodipine treatment. Two patients had shunting for ventricular enlargement and two patients had ventriculostomy. The follow-up study was done in two steps. All patients were examined in the outpatient department two months after discharge. A final assessment was made in the spring of 1990 by questionnaire or telephone call. All patients were traced. The mean follow-up period was 5.4 years (range from one to ten years). The follow-up grading was made using the Glasgow Outcome Scale (GOS)2~
Results Hypertensive blood pressure values were measured on admission in 16 cases in the S A H - N U D group ( > 100mmHg in diastole or > 180mmHg in systole). On admission 65 patients were clinical grade I, seven were grade II, ten were grade III and four were grade IV. CT scans were performed in 85 cases, during the first three days in 82% of cases and during the first
Table 3. Comparison of CT Findings in SAH Patients With ( N = 853) and Without (N = 86) Aneurysm 100
PER CENT %
80
Patients with head injuries, intracranial or intraspinal tumours, CNS infections, anticoagulant therapy, intracranial haematomas on CT scan, blood dyscrasia or atypical features of SAH were excluded frmn the present study. 996 patients with a clinical presentation of primary SAH were admitted to the University Hospital of Kuopio during 1980- 1989. Of these 996 patients, 86 had a negative panangiography study and formed the study group. Forty-seven were female. Age ranged from 14 to 69 years (mean age 51 years) (Table 2). No patient had a previous history of SAH. Fifteen patients had a history of arterial hypertension. Clinical grading on admission was performed according to Hunt and Hess 17. SAH was verified by lumbar puncture in 73 cases and by CT scan in 85 cases. CT findings were evaluated and graded according to Fisher 1~ Panangiographic studies were performed mainly by the transfemoral route. Control angiographies were done in 16 cases. All patients received symptomatic treatment for headache and were maintained on bedrest for 2 - 3 weeks, after which they were mobilized without any further restrictions. Antifibrinolytic agents were not used. Twenty patients received corticosteroids; ten patients had
60
40
20
0
NORMAL
SEVERESAH HYDROCEPPH.
! l
ANEURY$M
L
~
IVH
HAEMATOMA
NO ANEURYSM
Table 4. Comparison of Final Outcome ( GO S) in SAH Patients With ( N = 853) and Without ( N = 86) Aneurysm. ** All deaths are included. PER CENT
' ~ 1 7I6
%
[
86
80 60
Table 2_ Details of Patients in Aneurysm and Non-Aneurysm Groups 40
Aneurysm
No aneurysm
853 447 52% 406 48% 47 years 52 years
86 39 47 48 53
20
Total number Sex male female Mean age male female
45% 55% years years
6 0
3
GOOD RECOVERY MILD DISABILITYSEVERE DISABILITY
~ B ANEURYSM
~
NO ANEURYSM
3 DEATH-~
A. Ronkainen and J. Hernesniemi: Subarachnoid Haemorrhage of Unknown Aetiology Table 5. Persistent Symptoms drier Non-Aneurysmal SAH in 85 Patients
Patients
No symptoms Symptoms - headache - fatigue - memory defect - neurasthenic symptoms - dysphasia - vision defect
No.
Per cent
43 42 19 12 9 9 4 3
51% 49% 23% 14% 11% 11% 5% 4%
seven days in 93%. In a few cases the mildness of the presenting symptoms caused delay in diagnosis and CT scanning. In 29 cases the CT study was normal. Subarachnoid bleeding was considered minor in 32, moderate in 13 and severe in 11 cases (Table 3). All 86 panangiographies were normal. In 16 (19%) cases angiography was repeated with negative results, but with three angiographic complications. All of these three were related to vertebral angiographic studies. During the follow-up period, two patients had a second haemorrhage, one patient after two months and the other one four years later; at this time the angiographic study was again normal. Two male patients died from trauma and one male patient died from lung cancer. Fifty-four out of 64 (84%) working patients recovered totally and were able to return to full-time
31
work. Nine patients retired. Two patients (3%) had a p o o r outcome: a 44 year-old female already mentioned suffered severe, permanent postangiographic balance disturbances and ataxia, and a 64 year-old female sustained severe aphasia. Seventy-three (86%) patients made a good recovery and nine (11%) were left with a moderate disability (Table 4). In follow-up p r o f o r m a 42 (49 %) patients complained of various persistent subjective symptoms after SAH (Table 5).
D i s c u s s i o n
S A H - N U D is still frequent (up to 20% of SAH). Although neuroradiological methods have advanced greatly during the last twenty years, the nature of the bleeding point remains speculative. Compared to the p o o r prognosis of aneurysm-induced SAH, the present study confirms the benign character of S A H - N U D recorded in all reports 1-3' 5, 7-9, 14, 16, 19, 23, 24, 27--30, 32, 34--36, 39, 41, 44 (but only in comparison with the aneurysmal SAH). On admission 72 per cent of patients in the aneurysm group were in grades II and I I I as compared to 20 per cent of the S A H - N U D patients (the majority of whom were in grade I). In the S A H - N U D group, 84% of patients had a good recovery; this is consistent with all previous reports 1- 45 Due to the definition of this S A H - N U D group (negative panangiography), cases who might have the disease and die are never included, but this number of cases must be small. In our experience with more than 1,300 cases of primary SAH only two patients died without demonstrable aneurysms or AVMs at autopsy.
Fig. 1. Computed tomogram showing a small spot-like bleed behind the sella (a), medium-sizedsubarachnoid haemorrhage with ventricular enlargement (b), and a large subarachnoid bleed with hydrocephalus (c)
32
A. Ronkainen and J. Hernesniemi: Subarachnoid Haemorrhage of Unknown Aetiology
In this study we did not find any difference in the clinical states on admission, on CT scans or in final outcome between patients with high and normal blood pressure. Two patients were shunted for acute hydrocephalus. In the literature the incidence of acute hydrocephalus after S A H - N U D is 2 - 15 per cent and in the aneurysm group it is 30 per cent 8' 23. Our own figures for severe hydrocephalus are much smaller, being in the S A H - N U D group two per cent and in the aneurysm group eight per cent. Acute hydrocephalus associated with S A H - N U D is usually temporary, and treatment consists of repeated lumbar punctures. The need for a shunting operation is very rare. On admission we had 22 S A H - N U D patients with blood in the ventricular system, acute ventricular enlargement, or massive distribution of blood on CT scan. Ten of these 22 (45 %) were unconscious on admission: two were shunted and two had ventriculostomies. The clinical outcome was poor in this subgroup of 22, with two patients experiencing severe disabilities and three moderate disabilities, cf. 1' 10, 26. Patients with massive amounts of blood on CT comprise a small subgroup who are prone to a poor outcome and cerebral vasospasm, and might be the group with thrombosed aneurysms. We tried to evaluate different types of S A H - N U D bleeding from the CT pictures. In our opinion there is no one typical CT finding to rely on in diagnosing SAH-NUD, but rather three different main groups of CT findings can be seen (Figs. 1 a - c ) . In the patients with the type of bleeding shown in Figs. 1 a and 1 b, a rupture of small perforating vessels is suspected. The patients with severe bleeding (cf. Fig. 1 c) may represent the group of small or thrombosed aneurysms who are prone to spasm and poor outcome. Small AVMs or cervical AVMs are unlikely to be the bleeding point in a large number of cases. M R I studies in the future may further divide S A H - N U D into different subgroups. CT confirms SAH and provides information about a patient's prognosis, but it does not encourage the performance of exploratory surgery when the panangiographic study is negative. Even in these days of
Table 6. Reasonsfor Repeat Angiography Situation
Repeat angiography
Adequate primary study Inadequate primary study Rebleeding
no yes, immediately yes
sophisticated microsurgery we believe exploratory surgery in these cases is contraindicated 25. If thrombosed aneurysms or AVM are considered to be good treatment results in radiation of endovascular therapy, so also must be a cure achieved by nature. Repeat angiography is not required if the initial angiographic studies are properly done with adequate projections. A false negative rate should be less than two per cent 12' 14, 21, 36 (cf. Table 6). All sixteen of our repeat studies following adequate initial studies were negative, which is in agreement with earlier reports 3' 7, 8, 12, 19. In the present study, three patients experienced a complication after repeated vertebral angiography. In our experience, repeat angiography performed within 1 - 2 weeks after SAH is an investigation which engenders a high risk of severe complications differing from the usual complication rate in our department. In the case of an unsatisfactory angiographic study and high suspicion of aneurysm, a new study should of course be done immediately. Rebleeding, the rate varies from 0 to 10%, is only definite reason to repeat a late control study 3' 7--9, 14, 16 Patients with mild S A H - N U D can be mobilized within a few days, and patients with more severe clinical findings should be treated with effective medication to prevent vascular spasm and to control high blood pressure 9, 14, 21. We have used hypervolaemic-vasodilator medication in combination with bethamethasone to prevent late vasospasm; medical treatment is the same as for patients with operated aneurysms. In the long-term follow-up, 49% of patients complain about new symptoms after SAH; for the most part, these side-effects do not disturb normal life. Eskesen et al. found in their own study persistent symptoms in 84% of patients: headache in 44%, fatigue in 41%, dementia in 31%, and dysphasia in 17% 9. In the present study, patients had fewer complaints. Both studies give the same type of results for patients at long-term follow-up: most of the patients return to work, but many of them have some minor side-effects likely to persist for the rest of their life7. S/iveland et al. and Vilkki et al. have studied the outcome after aneurysmal SAH, and they report that only a very few patients will have a full recovery with no signs of psychosocial or cognitive disturbances 38' 42. We think that patients with S A H - N U D have very much the same problems, and that this result is seldom discussed and often overlooked. These patients with persistent sideeffects may need help and they should be identified and directed to further neuropsychological rehabili-
A. Ronkainen and J. Hernesniemi: Subarachnoid Haemorrhage of Unknown Aetiology t a t i o n . D e p r e s s i o n a n d a n x i e t y s h o u l d be t r e a t e d effectively by short-term medication.
References I. Alexander MSM, Dias PS, Uttley D (1986) Spontaneous subarachnoid haemorrhage and negative cerebral panangiography. J Neurosurg 64:537-542 2. Andrioli GC, Salar G, Rigobello L, Mingrino S (1979) Subarachnoid haemorrhage of unknown etiology. Acta Neurochir (Wien) 48:217 221 3. Beguelin C, Seiler R (1983) Subarachnoid haemorrhage with normal cerebral panangiography. Neurosurgery 13:409-411 4. Bj6rkesten af G, Halonen V (1965) Incidence of intra-cranial vascular lesion in patients with subarachnoid haemorrhage investigated by four-vessel angiography. J Neurosurg 1:29-32 5. Bj6rkesten af G, Troupp H (1957) Prognosis of subarachnoid haemorrhage a comparison between patients with verified aneurysms and patients with normal angiograms. J Neurosurg 14: 434.441 6. Bonita R, Thompson S (1985) Subarachnoid haemorrhage: epidemiology, diagnosis, management and outcome. Stroke 4: 591594
7. Brismar J, Sundb~irg G (1985) Subarachnoid haemorrhage of unknown origin: Prognosis and prognostic factors. J Neurosurg 63:349-354 8. Cioffi F, Pasqualin A, Cavazzani P, DaPian R (1989) Subarachnoid haemorrhage of unknown origin: clinical and tomographical aspects. Acta Neurochir (Wien) 97:31-39 9. Eskesen V, Sorensen E, Rosenorn J, Schmidt K (1984) The prognosis in subarachnoid haemorrhage of unknown etiology. J Neurosurg 61:1029-1031 10. Fisher CM, Kitler JP, Davis JM (1980) Relation of cerebral vasospasm to subarachnoid haemorrhage visualized by computerized tomographie scanning. J Neurosnrg 6:1-9 11. Fogelholm R (1981) Subarachnoid haemorrhage in Middle-Finland: incidence, early prognosis and indications for neurosurgical treatment. Stroke 12:296-301 12. Forster D, Steiner L, Hakanson S, Bergvall U (1978) The value of repeat pan-angiography in cases ofunex plained subarachnoid haemorrhage. J Neurosurg 48:712-716 I3. Gilbert J, Lee C, Young B (1990) Repeat cerebral pan-angiography in subarachnoid haemorrhage of unknown etiology. Surg Neurol 33:19-21 14. Giombini S, Bruzzone M, Pluchino F (1988) Subarachnoid haemorrhage of unexplaned cause. Neurosurgery 2:313-316 15. Gomez P, Lobato R, Rivas J, Cabrera A, Sarabia R, Castro S, Castaneda M, Canizal J (I989) Subarachnoid haemorrhage of unknown etiology. Acta Neurochir (Wien) 101:35-41 16. Hayward R (1977) Subarachnoid haemorrhage of unknown aetiology. A clinical and radiological study of 51 cases. J Neurol Neurosurg Psychiatry 40:926-931 17. Hunt WE, Hess RM (1968) Surgical risk as related to time of intervention in the repair ofintracranial aneurysms. J Neurosurg 28:14-20 I8. Iwanaga H, Wakai S, Ochiai C, Narita J, Inoh S, Nagai M (1990) Ruptured cerebral aneurysms missed by initial angiographic study. Neurosurgery 27:45-51
33
19. Jain V, Hedge T, Easwaran R Das B, Reddy G (1987) Benign subarachnoid haemorrhage. Subarachnoid haemorrhage of unknown aetiology. Acta Neurochir (Wien) 86:89-92 20. Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. A practical scale. Lancet 1:480-484 21. Juul R, Fredriksen T, Ringkjob R (1986) Prognosis in subarachnoid haemorrhage of unknown etiology. J Neurosurg 64: 359362 22. Juvela S, Kaste M, Hillbom M (1989) The effects of earlier surgery and shorter bedrest on the outcome in patients with subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 52: 776-777 23. Kawamura S, Yasui N (1990) Clinical and long-term follow-up study in patients with spontaneous subarachnoid haemorrhage of unknown aetiology. Acta Neurochir (Wien) 106:110-114 24. Levy L (1960) Subarachnoid haemorrhage without arteriographic vascular abnormality. J Neurosurg 17:252-258 25. Lorenzo N, Guidetti G (I988) Anterior communicating aneurysrns missed at angiography: report of two cases treated surgically. Neurosurgery 4:494-499 26. Mohsen F, Pomonis S, Illingwortb R (1984) Prediction of delayed cerebral ischaemia after subarachnoid haemorrhage by computed tomography. J Neurol Neurosurg Psychiatry 47: 1197-1202 27. Nishioka H, Torner J, Graf C, Kassell N, Sash A, Goettler L (1984) Cooperative study on intracranial aneurysms and subarachnoid haemorrhage: a long-term prognostic study II. Ruptured intracranial aneurysms managed conservativley. Arch Neurol 41:1142-1146 28. Oder W, Kollegger H, Zeiler K, Dal-Bianco P, Wessely P, Deecke L ( 1991) Subarachnoid haemorrhage o f unknown etiology: early prognostic factors for long-term functional capacity. J Neurosurg 74:601-605 29. Pakarinen S (1967) Incidence, aetiology, and prognosis of primary subarachnoid haemorrhage. Acta Neurol Scand 43 [Suppl 29]: 1-128 30. Rinkel G, Wijdieks E, Vermenlen M, Hageman I, Tans J, van Gijn J (1990) Outcome in perimesencephalic (nonaneurysmal) subarachnoid haemorrhage: a follow-up study in 37 patients. Neurology 40:1130-1132 3 I. Sarti C, Tuomilehto J, Narva E, Salmi K, Sivenius J, Kaarsalo E (1990) Epidemiology of subarachnoid haemorrhage in Finland during years 1982 - 85. First European Stroke Conference, Diisseldorf. J Neurology 237:142 32. Shepard R (1984) Prognosis of spontaneous (non-traumatic) subarachnoid haemorrhage of unknown cause. Lancet 7: 777778 33. Sonesson B, S/iveland H, Ljunggren B, Brandt L (1989) Cognitive functioning after subarachnoid haemorrhage of unknown origin. Acta Neurol Scand 80:400-410 34. Spaltone A, Ferrante L, Palatisky E, Santoro A, Acqui M (1986) Subarachnoid haemorrhage of unknown origin. Acta Neurochir (Wien) 80:12-17 35. Standnes B, Heilo A (1980) Subarachnoid haemorrhage of unknown etiology. J Oslo City Hosp 30:151-152 36. Sundbfirg G, Brismar J, Ljunggren B (1982) SAH of unknown origin. A good-natured catastrophe. Acta Neurochir (Wien) 66: 251 37. Suzuki S, Kayama T, Sakurai Y, Ogawa A, Suzuki J (1987) Subarachnoid haemorrhage of unknown cause. Neurosurgery 21:310-313
34
A. Ronkainen and J, Hernesniemi: Subarachnoid Haemorrhage of Unknown Aetiology
38. S/ireland H, Sonesson B, Ljunggren B, Brandt L, Uski T, Zygmunt S, Hindfelt B (1986) Outcome evaluation following subarachnoid haemorrhage. J Neurosurg 64:191-196 39. Tappura M (1962) Prognosis of subarachnoid haemorrhage: a study of 120 patients with unoperated vascular lesions demonstrable in bilateral carotid angiograms. Acta Med Scand [Suppl] 392:1-75 40. van Gijn J, van Dongen K (1980) Computerized tomography in subarachnoid haemorrhage: difference between patients with and without an aneurysm on angiography. Neurology 30: 538539 41. van Gijn J, van Dongen K, Vermeulen M, Hijdra A (1985) Perimesencephalic haemorrhage: a nonaneurysmal and benign from of subarachnoid haemorrhage. Neurology 35:493-497 42. Vilkki J, Holst P, Ohman J, Servo A, Heiskanen O (1990) Social outcome related to cognitive performance and computed tomo-
graphic findings after surgery for a ruptured intracranial aneurysm. Neurosurgery 4:579-585 43. West H, Mani R, Eisenberg R, Tuerk K, Stucker T (1977) Normal cerebral arteriography in patients with spontaneous subarachnoid haemorrhage. Neurology 27:592-594 44. Wijdicks E, Kerkhoff H, van Gijn J (1988) Long-term followup of 71 patients with thunderclap headache mimicking subarachnoid haemorrhage. Lancet 9:68-70 45. Yoshida M, Anegawa S, Moritaka K (1981) Significance of infundibular dilatation in unexplained subarachnoid haemorrhage. Neurosurgery 6:718-721
Correspondence and Reprints: Antti Ronkainen, M.D., Department of Neurosurgery, University Hospital of Kuopio, SF-70210 Kuopio, Finland.
Acta Neurochir (Wien) (1992) 119:29-34
9 Springer-Verlag 1992 Printed in Austria
Subarachnoid Haemorrhage of Unknown Aetiology A~ Ronkainen and J. Hernesniemi Department of Neurosurgery, University Hospital of Kuopio, Kuopio, Finland
Summary Eighty-six of 996 patients with primary subarachnoid haemorrhage (SAH) had negative panangiography studies. These 86 patients with subarachnoid haemorrhage of unknown origin (SAHNUD) were compared with 853 patients sustaining an aneurysmal bleed (SAH-A) admitted during the same period 1980- 1989. The age and sex distribution of both groups were similar. The SAHNUD group was in better condition on admission, with less blood evident on CT scan. All 16 (repeat control) angiography studies in the SAH-NUD group were negative. During a follow-up period ranging from 1 to 10 years (mean 5.4 years), two patients experienced rebleeding with negative repeat angiographies and subsequent total recovery. Using the Glasgow Outcome Scale (GOS) the final outcome
was good in 86% of the study group and 54% of the aneurysm group. However, half of the SAH-NUD patients complained of persistent symptoms at long-term follow-up. Thus, despite a generally good prognosis, for a given individual SAH-NUD may be catastrophic with many residual symptoms persisting for the rest of the person's life. Keywords: Subarachnoid haemorrhage; negative panangiography; unknown aetiology.
Introduction N o w a d a y s i n m o r e t h a n 4/5 & p a t i e n t s w i t h p r i m a r y subarachnoid haemorrhage (SAH) the bleeding point
Table 1. Aetiology o f Non-Traumatic S A H
Year
SAH
Aneurysm
AVM
Total
No.
%
No.
104l 140 113 94 849 308 529 369 469 1322 1180 814 50 120 996
901 80 84 68 760 256 339 288 424 1192 815 763 42 92 853
87% 57% 74% 72% 90% 83% 64% 78% 90% 90% 69 % 94% 84% 77% 86%
- - * 22 6 3 - - ** 8 40 23 - - * 58 104 5 - -* - -* 57
8394
6957
83%
326
SAH-NUD %
No.
%
no,
Aleksander etal. Andrioli etal. Bj6rkesten etal. Bonita et al. Cioffi et al. Eskesen et al. Forster et al. Giombini etal. Iwanaga et al. Kawamura etal. Shephard Suzuki et al. Van Gijn etal. Van Gijn etal. Present study
1986 1979 1964 1985 1989 1984 1978 1988 1990 1990 1984 1987 1980 1985 1990
Total: - - * Excluded from the study. - - ** Statistics are missing.
6%
140 38 17 23 65 44 150 58 37 72 261 41 8 28 86
13% 27% I5% 24% 8% I4% 28% 16% 8% 5% 22 % 5% 16% 23% 9%
6%
1068
13%
16% 5% 3% 3% 8% 6% 4% 9% 0.6%
30
A. Ronkainen and J. Hernesniemi: Subarachnoid Haemorrhage of Unknown Aetiology
can be demonstrated either by CT scan, cerebral angiography or M R I study (Table 1) 1' 2, 4, 16, 19, 43. In the days when angiography was the only neuroradiological method available, the group of patients with subarachnoid haemorrhage of unknown aetiology (SAH-NUD) was heterogeneous and formed a high percentage (up to 46 per cent) of patients with SAH 24. Cases of spontaneous intracerebral haematomas, tumours, cerebral contusions and undiagnosed aneurysms (especially in the posterior circulation, as many series included patients without vertebral angiograms) were included in even the most sophisticated series. Nowadays with CT scans S A H - N U D seems to be a well-defined group. This subgroup of SAH has a good prognosis without any specific treatment I' 5, 29, 34, 35, 39 and rebleeding occurs very s e l d o m 2' 14, 19, 23, 24 For unknown reasons the incidence of SAH in Finland is one of the highest in the world ~I' 31. We have evaluated the natural history of SAH-NUD, correlated clinical and CT findings with those of SAH-A and followed up the patients carefully to determine the final outcome of the disease. Patients and Methods
nimodipine treatment. Two patients had shunting for ventricular enlargement and two patients had ventriculostomy. The follow-up study was done in two steps. All patients were examined in the outpatient department two months after discharge. A final assessment was made in the spring of 1990 by questionnaire or telephone call. All patients were traced. The mean follow-up period was 5.4 years (range from one to ten years). The follow-up grading was made using the Glasgow Outcome Scale (GOS)2~
Results Hypertensive blood pressure values were measured on admission in 16 cases in the S A H - N U D group ( > 100mmHg in diastole or > 180mmHg in systole). On admission 65 patients were clinical grade I, seven were grade II, ten were grade III and four were grade IV. CT scans were performed in 85 cases, during the first three days in 82% of cases and during the first
Table 3. Comparison of CT Findings in SAH Patients With ( N = 853) and Without (N = 86) Aneurysm 100
PER CENT %
80
Patients with head injuries, intracranial or intraspinal tumours, CNS infections, anticoagulant therapy, intracranial haematomas on CT scan, blood dyscrasia or atypical features of SAH were excluded frmn the present study. 996 patients with a clinical presentation of primary SAH were admitted to the University Hospital of Kuopio during 1980- 1989. Of these 996 patients, 86 had a negative panangiography study and formed the study group. Forty-seven were female. Age ranged from 14 to 69 years (mean age 51 years) (Table 2). No patient had a previous history of SAH. Fifteen patients had a history of arterial hypertension. Clinical grading on admission was performed according to Hunt and Hess 17. SAH was verified by lumbar puncture in 73 cases and by CT scan in 85 cases. CT findings were evaluated and graded according to Fisher 1~ Panangiographic studies were performed mainly by the transfemoral route. Control angiographies were done in 16 cases. All patients received symptomatic treatment for headache and were maintained on bedrest for 2 - 3 weeks, after which they were mobilized without any further restrictions. Antifibrinolytic agents were not used. Twenty patients received corticosteroids; ten patients had
60
40
20
0
NORMAL
SEVERESAH HYDROCEPPH.
! l
ANEURY$M
L
~
IVH
HAEMATOMA
NO ANEURYSM
Table 4. Comparison of Final Outcome ( GO S) in SAH Patients With ( N = 853) and Without ( N = 86) Aneurysm. ** All deaths are included. PER CENT
' ~ 1 7I6
%
[
86
80 60
Table 2_ Details of Patients in Aneurysm and Non-Aneurysm Groups 40
Aneurysm
No aneurysm
853 447 52% 406 48% 47 years 52 years
86 39 47 48 53
20
Total number Sex male female Mean age male female
45% 55% years years
6 0
3
GOOD RECOVERY MILD DISABILITYSEVERE DISABILITY
~ B ANEURYSM
~
NO ANEURYSM
3 DEATH-~
A. Ronkainen and J. Hernesniemi: Subarachnoid Haemorrhage of Unknown Aetiology Table 5. Persistent Symptoms drier Non-Aneurysmal SAH in 85 Patients
Patients
No symptoms Symptoms - headache - fatigue - memory defect - neurasthenic symptoms - dysphasia - vision defect
No.
Per cent
43 42 19 12 9 9 4 3
51% 49% 23% 14% 11% 11% 5% 4%
seven days in 93%. In a few cases the mildness of the presenting symptoms caused delay in diagnosis and CT scanning. In 29 cases the CT study was normal. Subarachnoid bleeding was considered minor in 32, moderate in 13 and severe in 11 cases (Table 3). All 86 panangiographies were normal. In 16 (19%) cases angiography was repeated with negative results, but with three angiographic complications. All of these three were related to vertebral angiographic studies. During the follow-up period, two patients had a second haemorrhage, one patient after two months and the other one four years later; at this time the angiographic study was again normal. Two male patients died from trauma and one male patient died from lung cancer. Fifty-four out of 64 (84%) working patients recovered totally and were able to return to full-time
31
work. Nine patients retired. Two patients (3%) had a p o o r outcome: a 44 year-old female already mentioned suffered severe, permanent postangiographic balance disturbances and ataxia, and a 64 year-old female sustained severe aphasia. Seventy-three (86%) patients made a good recovery and nine (11%) were left with a moderate disability (Table 4). In follow-up p r o f o r m a 42 (49 %) patients complained of various persistent subjective symptoms after SAH (Table 5).
D i s c u s s i o n
S A H - N U D is still frequent (up to 20% of SAH). Although neuroradiological methods have advanced greatly during the last twenty years, the nature of the bleeding point remains speculative. Compared to the p o o r prognosis of aneurysm-induced SAH, the present study confirms the benign character of S A H - N U D recorded in all reports 1-3' 5, 7-9, 14, 16, 19, 23, 24, 27--30, 32, 34--36, 39, 41, 44 (but only in comparison with the aneurysmal SAH). On admission 72 per cent of patients in the aneurysm group were in grades II and I I I as compared to 20 per cent of the S A H - N U D patients (the majority of whom were in grade I). In the S A H - N U D group, 84% of patients had a good recovery; this is consistent with all previous reports 1- 45 Due to the definition of this S A H - N U D group (negative panangiography), cases who might have the disease and die are never included, but this number of cases must be small. In our experience with more than 1,300 cases of primary SAH only two patients died without demonstrable aneurysms or AVMs at autopsy.
Fig. 1. Computed tomogram showing a small spot-like bleed behind the sella (a), medium-sizedsubarachnoid haemorrhage with ventricular enlargement (b), and a large subarachnoid bleed with hydrocephalus (c)
32
A. Ronkainen and J. Hernesniemi: Subarachnoid Haemorrhage of Unknown Aetiology
In this study we did not find any difference in the clinical states on admission, on CT scans or in final outcome between patients with high and normal blood pressure. Two patients were shunted for acute hydrocephalus. In the literature the incidence of acute hydrocephalus after S A H - N U D is 2 - 15 per cent and in the aneurysm group it is 30 per cent 8' 23. Our own figures for severe hydrocephalus are much smaller, being in the S A H - N U D group two per cent and in the aneurysm group eight per cent. Acute hydrocephalus associated with S A H - N U D is usually temporary, and treatment consists of repeated lumbar punctures. The need for a shunting operation is very rare. On admission we had 22 S A H - N U D patients with blood in the ventricular system, acute ventricular enlargement, or massive distribution of blood on CT scan. Ten of these 22 (45 %) were unconscious on admission: two were shunted and two had ventriculostomies. The clinical outcome was poor in this subgroup of 22, with two patients experiencing severe disabilities and three moderate disabilities, cf. 1' 10, 26. Patients with massive amounts of blood on CT comprise a small subgroup who are prone to a poor outcome and cerebral vasospasm, and might be the group with thrombosed aneurysms. We tried to evaluate different types of S A H - N U D bleeding from the CT pictures. In our opinion there is no one typical CT finding to rely on in diagnosing SAH-NUD, but rather three different main groups of CT findings can be seen (Figs. 1 a - c ) . In the patients with the type of bleeding shown in Figs. 1 a and 1 b, a rupture of small perforating vessels is suspected. The patients with severe bleeding (cf. Fig. 1 c) may represent the group of small or thrombosed aneurysms who are prone to spasm and poor outcome. Small AVMs or cervical AVMs are unlikely to be the bleeding point in a large number of cases. M R I studies in the future may further divide S A H - N U D into different subgroups. CT confirms SAH and provides information about a patient's prognosis, but it does not encourage the performance of exploratory surgery when the panangiographic study is negative. Even in these days of
Table 6. Reasonsfor Repeat Angiography Situation
Repeat angiography
Adequate primary study Inadequate primary study Rebleeding
no yes, immediately yes
sophisticated microsurgery we believe exploratory surgery in these cases is contraindicated 25. If thrombosed aneurysms or AVM are considered to be good treatment results in radiation of endovascular therapy, so also must be a cure achieved by nature. Repeat angiography is not required if the initial angiographic studies are properly done with adequate projections. A false negative rate should be less than two per cent 12' 14, 21, 36 (cf. Table 6). All sixteen of our repeat studies following adequate initial studies were negative, which is in agreement with earlier reports 3' 7, 8, 12, 19. In the present study, three patients experienced a complication after repeated vertebral angiography. In our experience, repeat angiography performed within 1 - 2 weeks after SAH is an investigation which engenders a high risk of severe complications differing from the usual complication rate in our department. In the case of an unsatisfactory angiographic study and high suspicion of aneurysm, a new study should of course be done immediately. Rebleeding, the rate varies from 0 to 10%, is only definite reason to repeat a late control study 3' 7--9, 14, 16 Patients with mild S A H - N U D can be mobilized within a few days, and patients with more severe clinical findings should be treated with effective medication to prevent vascular spasm and to control high blood pressure 9, 14, 21. We have used hypervolaemic-vasodilator medication in combination with bethamethasone to prevent late vasospasm; medical treatment is the same as for patients with operated aneurysms. In the long-term follow-up, 49% of patients complain about new symptoms after SAH; for the most part, these side-effects do not disturb normal life. Eskesen et al. found in their own study persistent symptoms in 84% of patients: headache in 44%, fatigue in 41%, dementia in 31%, and dysphasia in 17% 9. In the present study, patients had fewer complaints. Both studies give the same type of results for patients at long-term follow-up: most of the patients return to work, but many of them have some minor side-effects likely to persist for the rest of their life7. S/iveland et al. and Vilkki et al. have studied the outcome after aneurysmal SAH, and they report that only a very few patients will have a full recovery with no signs of psychosocial or cognitive disturbances 38' 42. We think that patients with S A H - N U D have very much the same problems, and that this result is seldom discussed and often overlooked. These patients with persistent sideeffects may need help and they should be identified and directed to further neuropsychological rehabili-
A. Ronkainen and J. Hernesniemi: Subarachnoid Haemorrhage of Unknown Aetiology t a t i o n . D e p r e s s i o n a n d a n x i e t y s h o u l d be t r e a t e d effectively by short-term medication.
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A. Ronkainen and J, Hernesniemi: Subarachnoid Haemorrhage of Unknown Aetiology
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Correspondence and Reprints: Antti Ronkainen, M.D., Department of Neurosurgery, University Hospital of Kuopio, SF-70210 Kuopio, Finland.
