Chapter Five. Anosmia after aneurysmal subarachnoid hemorrhage. M.J.H. Wermer, M. Donswijk, P. Greebe, B. Verweij and G.J.E.

Transcription

1 Chapter Anosmia after aneurysmal subarachnoid hemorrhage M.J.H. Wermer, M. Donswijk, P. Greebe, B. Verweij and G.J.E. Rinkel

2 Abstract Background and purpose Anosmia has an important impact on well-being, but is often neglected by physicians. In patients with subarachnoid hemorrhage (SAH) anosmia has been reported mainly after surgery for aneurysms of the anterior communicating artery (ACA). We studied the prevalence, predisposing factors (aneurysm site and type of treatment), impact and prognosis of anosmia in SAH patients. Chapter Methods From those SAH patients who resumed independent living, we included all patients treated by between 1997 and 2003 and a sample of patients treated by between 1985 and Patients underwent structured interviews regarding the presence and duration of anosmia. The impact of anosmia was scored on a visual analog scale (VAS) ranging from zero (no influence) to 100 (the worst thing ever). Risk factors for anosmia were assessed by logistic regression analysis. Results Overall 89 (28% [95% CI 23-34%]) of the 315 interviewed patients reported anosmia after the SAH (mean follow-up 7.4 years); 10 (15%) of the 67 coiled patients and 79 (32%) of the 248 clipped patients. The median VAS impact score was 53 (range 0-100). In 20 of the 89 patients (23% [95% CI 15-33]) the symptoms had improved over time. Risk factors for anosmia were treatment by (OR 2.7 [95% CI ]) and ACA aneurysms (OR 2.0 [95% CI ]). Conclusions Anosmia after SAH has a high prevalence, a considerable impact and a poor prognosis. Its occurrence after suggests that not only damage to the olfactory nerve by but also the SAH itself plays a role in its pathogenesis. 60

3 Introduction Loss of smell (anosmia) has an important impact on the quality of life and on nutritional intake. Commonly reported problems from anosmia are safety issues, such as not perceiving potentially toxic environmental substances or spoiled food, and interpersonal relations, such as insecurity about one s own body odor and impaired sexual life. 1 Anosmia has been reported in surgically treated patients who have recovered after aneurysmal subarachnoid hemorrhage (SAH), especially in patients with a ruptured aneurysm of the anterior communicating artery, 2 but also in patients treated for aneurysms at other sites via the frontotemporal approach. 3 In patients with anterior communicating artery aneurysms the prevalence of anosmia has been reported to vary with the neurosurgical approach, 4 which suggests that brain retraction of the frontal lobe or direct pressure from spatula at the olfactory bulb or nerve during of the aneurysm plays an important role in the development of anosmia. Anosmia has, however, also been reported after neurovascular decompression for trigeminal neuralgia performed in sitting position 5, which indicates that not only direct damage but also traction from brain shift can cause anosmia. Whether aneurysmal rupture itself can also cause anosmia and whether anosmia occurs after endovascular treatment of aneurysms is unknown. Also, the prognosis of anosmia after SAH is unclear, because no follow-up studies exist that investigated the long-term outcome of anosmia. The objective of our study was to determine the prevalence, the impact and prognosis of anosmia in patients who have been treated for a ruptured aneurysm. By comparing the prevalence in clipped and coiled patients and in aneurysms at different locations we tried to identify causal factors in the development of anosmia. Methods Patients Patients who had been treated by between 1997 and 2003 or by between 1985 and 2001 in the University Medical Center Utrecht (UMCU) were eligible for our study. We included patients who met the following inclusion criteria 1) subarachnoid hemorrhage confirmed by CT or lumbar puncture; 2) presence of a saccular aneurysm confirmed by conventional angiography or CT- angiography; 3) treatment of the ruptured aneurysm; 4) age at time of SAH 18 years and 5) discharge to home or a rehabilitation facility. The clipped patients had been enrolled in a long-term follow-up study on the incidence of recurrent SAH. 7 The clipped patients were a sample of participants of this follow-up study; only patients who were enrolled after January 2004 were asked to participate in the anosmia study. Not eligible for the study were patients who resided in a nursing home, who were not able to communicate well 61

4 enough to give informed consent, or who were treated by both and. Patients who reported to have had loss of smell before the SAH were excluded from the analysis. Data-extraction and questionnaires Chapter We recorded the age and gender of the patients, the mode of treatment, the number of treatments and the location and size of the ruptured and additional aneurysms. Aneurysm locations were categorized into: 1) anterior cerebral artery (ACA) including the anterior communicating artery and pericallosal arteries; 2) internal carotid artery (ICA) containing the ophthalmic, posterior communicating, anterior choroidal arteries and the carotid T junction; 3) middle cerebral artery (MCA) and the 4) vertebrobasilar system. For the aneurysms located at the anterior communicating artery and the pericallosal artery we retrieved operation reports and categorized the neurosurgical approach into: a) frontotemporal approach or b) anterior interhemispheric approach. Patients underwent a standardized, semi-structured interview in which a self-developed questionnaire was administered by one of three researchers (MW, PG, MD). The coiled patients were all interviewed by telephone. The clipped patients 70 years of age were interviewed at the outpatient clinic, the patients older than 70 were interviewed by telephone. The researchers did five of the interviews together at the start of the study to reduce possible interobserver variation. The questionnaire comprised questions on whether patients had noticed any degree of loss of smell and/or taste after the SAH. Patients were asked whether there had been some degree of recovery and if so, after what time recovery had occurred. The impact of anosmia on quality of life was assessed on a visual analogue scale (VAS) by placing a mark on a vertical scale which ranges from zero (no influence on their lives at all) to 100 (the worst thing ever happened to them). Patients who were interviewed by telephone were asked to rate the impact on quality of life on a scale from zero to 100 instead of placing a mark. Data-analysis Descriptive statistics were performed by SPSS (version 11.5). We used logistic regression analysis to calculate odds ratios (OR) of characteristics associated with anosmia. The following factors were included in the analyses: age at time of SAH (continuous), gender, location of the ruptured aneurysm (categorical: internal carotid artery [ICA], anterior cerebral artery [ACA], medial cerebral artery [MCA], vertebrobasilar and dichotomous: ACA versus other locations), neurosurgical approach (only for anterior and pericallosal aneurysms), size of the ruptured aneurysm (dichotomous 10 millimeters and > 10 millimeters), number of aneurysms at the time of SAH (dichotomous: one versus multiple) and total number of treatments for the ruptured and additional aneurysms. We performed univariate regression analysis for all risk factors and multivariate regression analysis with forward selection of variables with probability values < 0.20 in the univariate analysis. Data were reported with 95% confidence intervals (CI). 62

5 Results Patients Eighty-two coiled patients were eligible for the study; of these 82 coiled patients 14 were lost to follow-up and one declined participation. Of the 776 eligible clipped patients, 502 were not included because they had been enrolled in the follow-up study of recurrent SAH before 2004 and 24 were lost to follow-up. Of the remaining 250 patients none declined participation, but two had pre-existent anosmia and were therefore excluded from the analysis. Thus, we included 315 patients; 67 (21%) had been treated by and 248 (79%) by. The mean age of the patients at the time of the interview was 60.3 years (range 25 91) and 199 (63%) of them were women. The mean follow-up time after the SAH was 7.4 years (median 5.7 range ). The baseline characteristics of the included patients are shown in Table 1. Incidence, impact and prognosis of anosmia Eighty-nine (28% [95% CI 23-34]) of the 315 patients reported to have had loss of smell after treatment for SAH; 10 (15% [95% CI 8-26]) of the 67 coiled patients and 79 (32% [95% CI 26-38]) of the 248 clipped patients (Table 2). The mean age of the patients with anosmia was 60.8 years (range 26-82) and 50 (56.2%) of them were women. In 48 (54%) of these patients the ruptured aneurysm was located at the ACA, in 17 (19%) at the MCA, in 17 (19%) at the ICA and in seven (8%) at the vertebrobasilar system. Of the 89 patients with anosmia, 15 said they were not able to express the impact of anosmia on a scale from 0 to 100. The remaining 74 patients evaluated the impact on life with a median of 53 on a scale from zero to 100 (mean 55, SD 29.3, range zero-100). Twenty (23% [95% CI 15-33]) of the 89 patients had noticed some degree of recovery over time; improvement had occurred in 13 (16%) of the 79 clipped patients and seven (70%) of the 10 coiled patients (difference between proportions 54% [95% CI 24-83). The median interval between SAH and onset of recovery was six months (SD 26.0, range 1-80). Three patients reported some degree of recovery more than a year after the SAH, in all other patients improvement occurred within the first year. 63

6 Table 1 Baseline characteristics of the 315 participants Coiled patients N=67 Clipped patients N=248 Women 41 (61.2%) 158 (63.7%) Mean age at time of SAH ±SD 52.4 ± ± 12.5 Chapter Mean time after SAH ± SD 3.5 ± ± 4.8 Location ruptured aneurysm* ACA -Anterior cerebral artery -Acom -Pericallosa MCA ICA VB Size of ruptured aneurysm 10 mm > 10 mm Unknown 20 (30%) (36%) 2 (3%) 21 (31%) 24 (36%) 16 (24%) 27 (40%) 117 (47%) (23%) 60 (24%) 15 (6%) 49 (20%) 87 (35%) 112 (45%) Number of aneurysms at SAH 1 > 1 with ipsilateral aneurysms > 1 with contralateral aneurysms 51 (76%) 9 (14%) 7 (10%) 222 (90%) 13 (5%) 13 (5%) *ACA= anterior cerebral artery including the anterior communicating artery and pericallosal arteries MCA= medial cerebral artery ICA= internal communicating artery VB= vertebrobasilar system Risk factors for anosmia In the univariate regression analysis treatment by means of (OR 2.7, 95% CI ) and treatment of a ACA aneurysm (OR 2.2, 95% CI ) were statistically significant related with anosmia. Gender (OR for men 0.7, 95% CI ) and the presence of multiple aneurysms at the time of the SAH (OR 1.7, 95% CI ) were not statistically significant factors in the univariate analyses but had a p-value of < 0.2 and were therefore included in the multivariate analyses. For patients with anterior and pericallosal aneurysms, the risk of anosmia was higher when treated by the frontotemporal approach compared to the anterior interhemispheric approach, but this difference was not statistically significant (OR 1.3; 95% CI ) In the multivariate regression analysis, treatment by means of (OR 2.7, 95% CI ) and treatment of a ACA aneurysm (OR 2.0, 95% CI ) were both statistically significant risk factors for anosmia. 64

7 Table 2 Anosmia in relation to type of treatment and location and size of the aneurysm Presence of anosmia (95% CI) All patients 28% (23-34) 32% (26-38) 15% (8-26) Location of the aneurysm ACA MCA ICA VB 35% (27-44) 38% (29-47) 20% (7-44) 27% (17-40) 28% (18-42) 0% 21% (13-32) 25% (15-39) 13% (3-33) 19% (9-37) 27% (9-55) 14% (4-37) Neurosurgical approach Acom and anterior aneurysms (n=110) frontotemporal (n= 93) anterior interhemispheric (n=0) unkown (n=17) Pericallosa aneuryms (n=7) frontotemporal (n=0) anterior interhemispheric (n=6) unknown (n=1) Size of the ruptured aneurysm (n=176) 10 millimeters >10 millimeters 38% (29-48) 39% (30-50) 0% 29% (11-56) 29% (5-70) 0% 33% (6-76) 0% 22% (13-33) 31% (19-46) 4% (0-23) 28% (20-38) 32% (23-43) 6% (0-32) ACA = Anterior cerebral artery including the anterior communicating artery and the pericallosal arteries MCA = Middle cerebral artery ICA = Internal carotid artery VB = Vertebrobasilar arteries 65

8 Discussion Chapter This study shows that the prevalence of anosmia is high in patients who have recovered from an aneurysmal SAH and in whom the aneurysm had been treated by means of neurosurgical or endovascular. One out of every three patients treated neurosurgically and one out of every six patients treated endovascularly reported anosmia, and in three out of every four patients anosmia was permanent. Recovery occurred more often after than after. The impact on patients well-being was rated as considerable. Risk factors for development of anosmia after endovascular or surgically treated SAH were ACA aneurysms and treatment by means of. Several studies previously reported on the frequency of anosmia following operation for aneurysms in the anterior circulation. The relation between this aneurysm location and anosmia is understandable due to the close anatomical relation of the anterior circulation and the olfactory tract. The prevalence found in these studies depended on the mode of aneurysm approach. Coming from the front, with the anterior interhemispheric approach (AIA), the frontal lobe is elevated and the olfactory tract must be extensively dissected. In this group, subjective anosmia was reported in 52 (55%) of 94 patients. 8 A variation of this approach is the (lower) anterior basal interhemispheric approach (ABIA), which enables a lesser extent of both dissection of the olfactory tract and frontal lobe elevation. In one study 1 (2%) of the 52 patients treated via the ABIA had postoperative anosmia compared to 15 (31%) of the 49 patients treated via the AIA. 4 However, drawbacks of these approaches are the lack of control of the circulation proximal from the aneurysm and pressure on the frontal lobes. A more favoured approach for aneurysms of the anterior communicating artery, also in our hospital, is the frontotemporal or pterional approach (FTA) (coming mostly from the temporal side) were vascular control is safer and the olfactory tract can be anatomically easier preserved and both sided injury is unlikely. Twenty-two of 25 patients (88%) operated for ruptured intracranial aneurysms by the FTA had postoperatively anosmia ipsilateral to the side of surgery. 3 However, in another study on the FTA, the functions of the olfactory nerve could be preserved in 85% of the 100 included patients by placing the retractor only against the frontal lobe and using an aperture of only centimeters. 2 In the majority of these studies anosmia was found with olfactory testing and was not reported by the patients themselves. In our study we found a higher risk of anosmia in aneurysms treated by the AIA (39%) compared to FTA (33%) but this difference was not statistically significant, probably because of the low number of patients treated by AIA. To our knowledge, no other studies reported on the impact and prognosis of anosmia after endovascular or surgically treated aneurysmal SAH or on the prevalence of anosmia after. The profound impact of anosmia on quality of life has been described in other studies. 1,9 In 17-29% of patients with anosmia signs of depression were found and overall satisfaction 66

9 with life was reported by only 50% of patients. 9 Commonly reported impairments by anosmia patients were inability to recognize spoiled food, gas leaks or fire and the decreased enjoyment of food and cooking. Furthermore, a good sense of smell was found to be important for personal hygiene, social interactions and sex life. 1 There are some limitations of our study that need to be acknowledged. The presence of anosmia after the SAH was assessed by means of a questionnaire. Deficits in smell could have been measured more objectively by means of standardized olfactory testing. There is, however, not one standard way of testing olfaction. In two studies that used both questionnaires and formal testing of olfaction, the correlation between subjective and objective test results was high. 4,8 The positive predictive value in both studies was 100%. The negative predictive value was 84% in the study that used five odors at eight concentration levels as testing of olfaction 8 and 64% in the study that used vanilla essence placement with contralateral occlusion as testing of olfaction. 4 These findings suggest that the use of questionnaires instead of formal olfactory tests in our study could have led to an underestimation of the prevalence of anosmia. Furthermore, because the nature of our study was retrospective, patients might have had problems to recall anosmia that had subsided during follow up. This also might have resulted in an underestimation of both the proportion of patients with anosmia and the prognosis of anosmia. Finally, we did not systematically exclude other causes of anosmia such as medication, nasal and sinus disease, trauma or early Parkinson s disease. 1 However, given the relation in time with the SAH (we asked for the presence of anosmia right after treatment for the ruptured aneurysm) we consider these other causes unlikely. Anosmia did not only occur in patients who had been treated by for an aneurysm of the anterior cerebral or communication artery, but also in patients treated by and in patients who had ruptured aneurysms at other sites than the anterior circulation. This suggests that direct mechanical damage to the olfactory nerve is not the only causal factor for anosmia. The olfactory nerve and olfactory bulb might also be damaged through contact with subarachnoid blood or by increased intracranial pressure at the time of the aneurysmal rupture. In patients with siderosis of the central nervous system, anosmia occurred in at least 17% of the patients. 10 Another possible causal factor for the development of anosmia might be ischemia of parts of the cerebral cortex involved in the processing of olfactory information. In a recent study, 10 (10%) out of 102 stroke patients with a first ever stroke had olfactory dysfunction. 11 In SAH patients cortical damage might develop as a consequence of an intracerebral hematoma from the aneurysmal rupture or as a consequence of delayed cerebral ischemia. Our study did not include patients with unruptured aneurysms. Assessing smell in treated and untreated patients with unruptured aneurysms could further unravel the role of treatment and subarachnoid blood in the pathogenesis of anosmia. In conclusion, anosmia after endovascular or surgically treated aneurysmal SAH has a widespread occurrence and an important impact on quality of life. It is likely that it often goes unrecognised by physicians and therefore more attention should be paid to this deficit in 67

10 the post-operative contact with SAH patients. The results of our study could help physicians in informing patients with anosmia about prognosis. More research is needed on the occurrence of anosmia in patients treated for unruptured aneurysms to further elucidate its pathophysiology. Chapter 68

11 References 1. Hummel T, Nordin S. Olfactory disorders and their consequences for quality of life. Acta Otolaryngol 2005;125: Aydin IH, Kadioglu HH, Tuzun Y, Kayaoglu CR, Takci E, Ozturk M. Postoperative anosmia after anterior communicating artery aneurysms surgery by the pterional approach. Minim Invasive Neurosurg 1996;39: Eriksen KD, Boge-Rasmussen T, Kruse-Larsen C. Anosmia following operation for cerebral aneurysms in the anterior circulation. J Neurosurg 1990;72: Fujiwara H, Yasui N, Nathal-Vera E, Suzuki A. Anosmia after anterior communicating artery aneurysm surgery: Comparison between the anterior interhemispheric and basal interhemispheric approaches. Neurosurgery 1996;38: Ramsbacher J, Vesper J, Brock M. Permanent postoperative anosmia: A serious complication of neurovascular decompression in the sitting position. Acta Neurochir (Wien) 2000;142: Wermer MJH, van der Schaaf IC, Velthuis BK, Algra A, Buskens E, Rinkel GJE. Follow-up screening after subarachnoid haemorrhage: Frequency and determinants of new aneurysms and enlargement of existing aneurysms. Brain 2005;128: Wermer MJH, Greebe P, Algra A, Rinkel GJE. Incidence of recurrent subarachnoid hemorrhage after for ruptured intracranial aneurysms. Stroke 2005;36: Suzuki J, Yoshimoto T, Mizoi K. Preservation of the olfactory tract in bifrontal craniotomy for anterior communicating artery aneurysms, and the functional prognosis. J Neurosurg 1981;54: Miwa T, Furukawa M, Tsukatani T, Costanzo RM, DiNardo LJ, Reiter ER. Impact of olfactory impairment on quality of life and disability. Arch Otolaryngol Head Neck Surg 2001;127: Fearnley JM, Stevens JM, Rudge P. Superficial siderosis of the central nervous system. Brain 1995;118: Heckmann JG, Stossel C, Lang CJ, Neundorfer B, Tomandl B, Hummel T. Taste disorders in acute stroke: A prospective observational study on taste disorders in 102 stroke patients. Stroke 2005;36: