Unruptured Intracranial Aneurysms

An aneurysm is formed when a region of the blood vessel wall or artery weakens and balloons out to form a sac-like structure (Figure 1). A UIA is classified as an aneurysm without historical or pathological evidence of a breach through the artery wall (Weir, 2002). The presence of an UIA can come to clinical attention in several ways, including discovery when investigating headaches, seizures or embolic events (Orz et al., 2000). UIAs can also be discovered when treating a ruptured aneurysm, or they may be found incidentally during the assessment of an unrelated problem (Orz et al., 2000). Differences in the manner in which UIAs come to clinical attention have led to variations in the terminology used to describe these aneurysms. For example, the term “symptomatic aneurysm” is used to describe aneurysms that rupture, or aneurysms that produce neurological symptoms by space occupying effects. “Asymptomatic aneurysms” are not responsible for clinical presentations and are typically found in patients with an additional symptomatic aneurysm, or when conducting investigations in patients who are at risk of harboring an aneurysm. “Incidental aneurysms” are those found unexpectedly in patients undergoing investigation for other suspected pathology (Wardlaw & White, 2000). In this paper the generic term “unruptured intracranial aneurysm” (UIA) is used to describe all three categories of unruptured aneurysm.

Radiographic image of an unruptured intracranial aneurysm.

Decisions to treat UIAs are said to depend on the relative risk of subsequent spontaneous rupture and SAH in untreated patients versus the risks of treatment (Orz et al., 2000). Unfortunately, accurate knowledge regarding the natural history of aneurysms is still lacking (Asari & Ohmoto, 1993; Juvela et al., 1993), although an annual rate of rupture of between 1–2% is in the main well accepted (Juvela et al., 2000). Several potential risk factors for aneurysm formation and rupture have been discussed extensively in the literature and the interested reader is referred to the excellent review article recently published in the Journal of Neurosurgery (Weir, 2002). Briefly, increasing aneurysm size and aspect ratio have been hypothesized to present a significant risk in terms of intrinsic features of the aneurysm itself whilst cigarette smoking, alcohol intake and high life event stress appear to present the greatest risk in terms of modifiable risk factors. Age is also thought to be an important risk factor with it suggested that the peak risk for aneurysm rupture occurs between the ages of 40 to 60 years (Samson, 1996). Factors related to pregnancy and hormone changes following menopause also appear to be important but at this stage are largely uninvestigated.

Outcome following treatment for an UIA is also still largely open to debate. Currently there are generally three main management techniques employed. These are surgical clipping, endovascular therapy with coiling and “best medical therapy,” otherwise known as conservative management (lifestyle modifications and ongoing monitoring). With both surgery and endovascular therapy (Figure 2) the aim is to exclude the aneurysm from the blood circulation to prevent future rupture and/or to relieve any symptoms of mass effect associated with the aneurysm (Molyneux, 2000), whilst at the same time not producing adverse cognitive or neurological symptoms. Additional factors that need to be considered when selecting the optimal treatment method are the cost of the treatment, length of hospital stay and duration of rest and recovery period (Martin, 1997).

Endovascularly coiled aneurysm (A) and surgically clipped aneurysm (B) (Johnston et al., 2000).

Mortality and Neurological Morbidity Following Surgical Treatment

Based on a review of 30 studies conducted between 1977 and 2001 (Table 1) the gross outcome following clipping of an unruptured aneurysm appears to be generally good. The range of reported morbidity and mortality values does, however, vary widely, falling anywhere between 0–7% for mortality and between 5–25% for morbidity. These variations can largely be accounted for by the differences in measures of morbidity used, time frame of assessment of outcome, exclusion and inclusion protocols for patient populations, and different demographics of patient populations.

Surgical and endovascular mortality and morbidity

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For example, studies with lower morbidity and mortality figures typically did not include larger aneurysms or poor risk candidates (Wirth et al., 1983). Poor surgical outcome is generally reported by studies that include patients with larger aneurysms, aneurysms in difficult-to-treat locations and aneurysms in the elderly (Solomon & Baker, 1992). Another variable affecting the mortality and morbidity figures is hospital volume, with those hospitals more frequently performing aneurysm operations having lower mortality (Solomon et al., 1996). These, and other methodological differences, make comparisons between the various studies problematic.

In order to overcome the limitations of many of the studies and the difficulty in comparing results, several investigators have opted to pool studies and conduct meta-analyses of the findings. Selection protocols for meta-analysis studies are typically rigorous and ensure that only studies with similar methodological protocols are compared. One such meta-analysis has been conducted by King et al. (1994). In their study only patients who had undergone surgery for incidental or multiple aneurysms were included, and all patients with symptomatic aneurysms were excluded. They also included only patients who had a good neurological status prior to treatment. Surgical mortality was defined as any death within 30 days of surgery. Morbidity was defined as a permanent significant neurological deficit and was based on the longest reported follow-up period. Their search of the literature produced a 28-case series containing a total of 733 eligible patients. They reported a range in morbidity rates from 0.0% to 16.7% and a range in mortality of 0.0% to 7.7%, with a combined morbidity of 4.1% and a mortality of 1.0%.

Raaymakers et al. (1998) have also conducted a meta-analysis of studies based on surgery for unruptured aneurysms, but with slightly different criteria to those of King et al. (1994). Unlike King et al. (1994), Raaymakers et al. (1998) included in their analysis studies of patients with symptomatic aneurysms and patients who had neurological signs or symptoms preoperatively. They also included higher proportions of posterior circulation aneurysms and giant aneurysms. The analysis of Raaymakers et al. (1998) included 61 studies with 2,460 patients. From these studies they reported a combined mortality of 2.6% and a permanent morbidity of 10.9%. They noted that morbidity percentages tended to be higher in studies they considered to be of “high” quality.

Recently the International Study of Unruptured Intracranial Aneurysm Investigators (ISUIA; 1988) conducted a large scale multi-center study of UIAs in which they found the morbidity and mortality figures for treatment of unruptured aneurysms to be much higher than previously reported by King et al. (1994), and slightly higher than those reported by Raaymakers et al. (1998). Morbidity and mortality figures were based on 996 cases that proceeded to surgery. Mortality was 1.8% 30 days after surgery and 3.6% 1 year after surgery. The ISUIA (1988) study is interesting and, at the time it was published, was the only study to have utilized cognitive as well as neurological measures of outcome. The measures used by the ISUIA (1988) study were the Telephone Interview for Cognitive Status (Brandt et al., 1988) and the Mini-Mental State Examination (Folstein et al., 1975). When based on the Rankin Disability Scale (Rankin, 1957) alone, a brief scale of functional outcome following a stroke, morbidity 30 days after surgery was 3.6%, and 1 year after surgery it was 2.9%. When based on cognitive status alone, 30 days after surgery morbidity was 6.3% and 1 year after surgery it was 6.1%. When based on either the Rankin scale, or cognitive status, or both, morbidity 30 days after surgery was 15.0% and one year after surgery it was 12.0%. Although at 1 year the patients without a history of SAH had a slightly poorer outcome in terms of overall morbidity, when it came to measures of cognitive status alone, patients with a history of SAH had a poorer outcome. The authors attributed this to the effect of three consecutive cerebral events (1 SAH and 2 craniotomies) on mental status. These findings raise several interesting points. First, basing measures of outcome on either neurological status or cognitive status alone can be misleading. Second, morbidity changes with time, and typically will improve given time. Studies that report morbidity figures based only on short follow-up periods may therefore result in overestimates of morbidity outcomes. Third, the ISUIA (1988) study fails to adequately control for the effect of other factors on morbidity, such as previous SAH.

In summary, the generally favorable outcome following surgery for unruptured aneurysms combined with extensive research demonstrating the poor outcome following the rupture of an aneurysm (Ogden et al., 1990, 1993, 1994) have been used to argue in favor of treatment of unruptured aneurysms to avoid the possibility of future rupture (Eskesen et al., 1988; Heiskanen, 1986; Mizoi et al., 1989). The ISUIA (1988) study concludes that mortality and morbidity rates following surgery for unruptured aneurysms are higher than the rate of spontaneous rupture if the UIA is left untreated. However this conclusion has been criticized by several researchers (Alexander & Spetzler, 1999; Debrun, 1999; Hashi, 1999; Kobayashi & Orz, 1999; Solomon, 1999). The ISUIA study does nonetheless raise the possibility that surgical risks might outweigh the benefits of occluding the aneurysm (Roy et al., 2001), and hence the controversy remains unresolved.

Mortality and Neurological Morbidity Following Endovascular Treatment

In contrast to the information available about surgical clipping, data on the effectiveness and risks of endovascular coil embolization for UIAs is more tentative (Wardlaw & White, 2000). This technique has only been in widespread use since 1991, and is undergoing constant refinement. Thus long-term follow-up is not yet well documented (Kahara et al., 1999; Lot et al., 1999). In addition, at this stage, endovascular coiling and surgical clipping tend to be used in different patient populations (Viñuela et al., 1997). For example, in most studies the indications for endovascular treatment remain that surgical treatment is unsuitable because of anatomical considerations, patient medical condition, or patient age. For this reason, how the two techniques compare in equivalent patient populations is as yet unknown (Johnston et al., 1999a). A more extensive analysis of the long-term results of treatment with endovascular coiling is considered to be particularly important as such a treatment may provide a less invasive alternative to surgery (Wardlaw & White, 2000).

Many of the existing studies on the efficacy of endovascular embolization using coiling have been conducted on SAH populations (Byrne et al., 1999; Casasco et al., 1993; Lempert et al., 2000; Vanninen et al., 1999; Viñuela et al., 1997), or on a combination of ruptured and unruptured cases where the two groups are not separately analyzed (Cognard et al., 1999; Raftopoulos et al., 2000; Steiger et al., 1999; Zubilaga et al., 1994). In other studies the numbers of UIAs in the various groups in the study are too small to make useful comparisons (Kahara et al., 1999; Redekop et al., 1999; Regli et al., 1999). Only a limited number of studies have reviewed coiling in samples consisting of UIAs. It has, however, been argued that studies of UIAs provide more useful information about treatment outcome than SAH studies because patients are generally minimally impaired and therefore any new deficits can be attributed to the treatment rather than the hemorrhage (Johnston et al., 2000). These UIA studies report a wide range of mortality percentages, from 0–13%, and morbidity percentages from 5–20% (see Table 1).

A recent meta-analysis of studies of embolization suggested that treatment-related complication rates are similar to those reported following surgery, with a morbidity of 3.7% and a mortality of 1% (Brilstra et al., 1999). Brilstra et al. (1999) however noted that longer-term results are needed before final conclusions can be drawn. This is particularly important because of the possibility of recanalization and rebleeding in incompletely occluded aneurysms. In addition it is unlikely that the group of patients treated endovascularly and reviewed in the meta-analysis by Brilstra et al. (1999) are equivalent to patients reviewed in studies of surgical outcome.

Comparing studies of outcome following coiling and clipping is problematical because the two treatment methods are not considered equally appropriate for every case. In addition Brilstra et al. (1999) advises caution when comparing the two techniques because of the widely heterogeneous nature of study designs, patients and aneurysms. A few studies have, however, attempted to compare outcome following the two procedures, although with varying conclusions. As an example Leber et al. (1998) concluded that coiling with Guglielmi electrolytically detachable coils (GDCs) is as safe and effective as clipping in cases of UIAs. However, it should be noted that in their study there were many more patients enrolled in the endovascular group than in the surgical group, with the reason for this not given.

In another study that compares endovascular and surgical outcome in a large multi-center cohort of patients with UIAs, Johnston et al. (1999a) conclude that adverse outcomes were significantly more common in surgical cases when compared to endovascular cases. Mortality, however, was not significantly affected by treatment type. The authors do acknowledge several limitations of their study. For example, an adverse outcome was defined as in-hospital death or transfer to a nursing home or rehabilitation hospital at discharge. As they note, recovery from surgery may be slower, but more complete, and this would not be reflected in their measure of adverse outcome. Further, although variables of gender, age, race and admission source (emergency room, transfer or elective), were controlled for statistically when comparing the two treatment groups, other important variables, such as aneurysm characteristics, could not be controlled for in the study (Johnston et al., 1999a). As noted by Johnston et al. (2000) in a later article, the previous study cannot rule out that better outcome following coiling was a result of the selection of lower risk candidates for this procedure. Nonetheless the authors concluded that despite the limitations of the study, the findings are important and provocative. Although they cannot provide a definitive basis for recommending coil embolization they do consider their study provides impetus for further studies comparing the two methods.

The later paper by Johnston et al. (2000) reports on a similar study conducted at a single institution. From that study the authors draw a very similar conclusion that endovascular treatment of UIAs seems to be significantly safer than surgical clipping. They found that surgery was associated with greater rates of early and persistent disability, more procedure-related complications and a greater delay in return of function. They do note, however, that the rupture of three aneurysms in the endovascular patients during follow-up compared with one in the surgical group highlights the need for longer-term follow-up. As with the first study they also note that there may be unmeasurable factors contributing to the differences between outcomes in groups (Johnston et al., 2000).

To summarize, it has been suggested that it might be too soon to make durable comparisons between surgical and endovascular methods as it is quite likely that the endovascular technique will continue to undergo further modifications, with alternative devices possibly providing more complete and stable aneurysm occlusion (Bavinzski et al., 1999). Combined studies may be particularly useful in evaluating the belief that the combination of surgical clipping and coiling in management protocols may help to improve the overall outcome of all cases (Johnston et al., 2000; Sturaitis et al., 2000). Combined approaches may also be particularly useful in cases of complex intracranial aneurysms often deemed too difficult for standard treatment (Hacein-Bey et al., 1997). As Martin (1998) comments, endovascular methods should be considered as a complementary method to surgery, rather than as a replacement method. They suggest endovascular options extend treatment to patients with inoperable or high-surgical-risk aneurysms.

Mortality and Morbidity Following Aneurysm Rupture

As mentioned earlier “best medical therapy,” or conservative management, is considered to be a viable option for the treatment of UIAs. However, this treatment option in itself carries a risk—the risk that the aneurysm may rupture at some point in the future. As already noted, rupture rates of between 1–2% per year are generally accepted. Unfortunately whilst the number of patients experiencing good outcome following the rupture of an aneurysm have increased in the last decade (Cesarini et al., 1999; Hop et al., 1997; Le Roux et al., 1995), fatality rates are still high. In the review conducted by Hop et al. (1997) case-fatality rates ranging between 32% to 67% were reported. Further, morbidity rates in those who survive a SAH also remain unacceptably high and are said to range between 40–50% (Dorsch, 2000; Samson, 1996).

Adding to the already dismal picture Hop et al. (1997) note many of the patients who remain “independent” after a SAH may experience difficulties returning to their former level of functioning. Many studies of reportedly “good” recovery patients, as determined by neurological outcomes scales, have revealed that many of these patients still demonstrate deficits in terms of cognitive functioning, psychosocial functioning and quality of life (Bornstein et al., 1987; Hop et al., 1998; Ljunggren et al., 1985; Ogden et al., 1990, 1993, 1994; Säveland et al., 1992).

In a study conducted by Ogden et al. (1990) 100% of the patients were rated as having achieved a good neurological recovery whilst only 37.5% were rated as having achieved a good neuropsychological outcome. All patients had achieved full physical independence but only 63% had returned to their previous level of leisure activities and only 50% had returned to their premorbid work levels. Other researchers have reported similar figures (Ropper & Zervas, 1984; Säveland et al., 1986; Tidswell et al., 1995). Further, a recent review of health outcome one year following SAH (Hackett & Anderson, 2000) likewise found that many patients continue to experience significant reductions in quality of life, and in particular in social role functioning. They also reported that between one-third to one-half of the patients reported ongoing subjective problems of memory and mood (Hackett & Anderson, 2000). Examples such as these, and the extensive experience in the field of SAH research again reinforces the importance of considering factors other than neurological outcome when evaluating the management of a particular disease process.

Another important area debated in the existing SAH literature, particularly in terms of predicting what we might expect to see following treatment of a UIA, is that of what processes underlie the observed poor cognitive outcome of many patients. SAH is considered to be a complex disorder involving the initial hemorrhage and a number of secondary events (Cesarini et al., 1999). It has been suggested that the considerably unfavorable outcomes that have been observed to follow SAH are to a large extent the consequence of secondary insults sustained by the brain during the acute phase of the disease (Cesarini et al., 1999).

Some evidence has been reported which suggests that observed neuropsychological deficits are related to the diffuse brain damage as disclosed on CT scan 1 year after SAH (Vilkki et al., 1990). However other investigations have failed to find a relationship between damage to the brain and cognitive disturbances in patients with reportedly good neurological outcome (Berry et al., 1997). Other factors associated with the surgical treatment of the aneurysm have also reportedly been found not to be associated with evidence of poor cognitive outcome (Berry et al., 1997). Indeed, from a study that reviewed the cognitive and psychological sequelae of uncomplicated aneurysm surgery, Maurice-Williams et al. (1991) concluded that uncomplicated surgery itself does not involve any risk of detectable impairment. Once again, however, there remains some controversy with other researchers who conclude that aspects of surgery to treat a SAH do correlate with longer-term cognitive disability (Tidswell et al., 1995).

A possible means of resolving some of this controversy may be to compare surgically clipped SAH cases to matched endovascularly coiled SAH cases. If differences in neuropsychological outcome are observed in these cases then it may be possible to argue that these differences are due to the treatment, assuming of course that the cases are well matched. If there are no differences between the two groups then it may in turn be appropriate to argue that any observed deficits are most likely due to shared factors, such as the diffuse damage from the original bleed, experience of hospitalization, anesthetic effects, etc. Some evidence on this controversy has recently been provided by Hadjivassiliou et al. (2001) who compared pairs of subarachnoid hemorrhage patients matched on factors other than treatment modality and found that coiling and clipping produced statistically similar impairments across a wide range of cognitive domains. In this study the authors concluded that such evidence suggested that the impairments in cognitive outcome observed to follow SAH were largely the result of the original hemorrhage. They do however also note that there was some evidence that surgical clipping produced more frontotemporal damage (Hadjivassiliou et al., 2001). In addition, the recent International Subarachnoid Aneurysm Trial (ISAT) study (2002) found the neurological morbidity in clipped SAH cases to be significantly worse than the neurological morbidity of endovascularly coiled SAH cases, suggesting that clipping produces some additional damage above and beyond the effects of the original bleed.

Another study design which can also shed useful light on the controversy is a design which compares neuropsychological outcome in well matched SAH and UIA cases. As Hillis et al. (2000) note such a study allows the neuropsychological effects which result from the SAH to be separated out from the neuropsychological deficits that result from the treatment, treatment complications, anesthesia and other factors such as psychological depression. From their study which utilized such a design they concluded that some specific deficits appeared to be related to the original SAH whereas other deficits were more likely related to the general effects of treatment (Hillis et al., 2000). Further investigations with study designs that incorporate clipped and coiled cases and/or SAH and UIA cases are clearly needed to shed further light on the relative contribution of initial SAH and subsequent treatment to the profile of cognitive deficits often observed to follow rupturing of an aneurysm.

In addition to the cognitive deficits experienced by many victims of SAH a considerable number of recovered patients also report psychological deficits. With regard to the processes that may underlie these deficits it has been hypothesized that the poor social and psychological outcome observed in SAH victims may result from the subjective experience of suffering from a SAH (McKenna et al., 1989; Ogden et al., 1990; Vilkki et al., 1990). An interesting finding from the study conducted by Ogden et al. (1990) was that the group of patients for whom an aneurysm could not be identified experienced significantly poorer outcomes on several psychosocial variables. From this Ogden et al. (1990) hypothesized that because these patients could not be reassured that an aneurysm had been occluded, psychological rather than neuropsychological processes may underlie some aspects of recovery. If part of the outcome picture typically observed to follow SAH without an identifiable aneurysm can be attributed to psychological repercussions of having suffered a life-threatening illness, then we might expect to see some deficits following discovery of an UIA. Again, however, a thorough investigation is needed to confirm this.

Neuropsychological and Psychosocial Outcome Following Treatment of UIAs

Physicians are schooled in the tradition of “first do no harm.” But what do we consider to be harm? To a large extent measurement and significance of postoperative outcome depends on the measure of outcome used (Raaymakers, 2000). Raaymakers notes that outcome measures, or measures of harm, have generally been restricted to measures of neurological impairment. Typically assessments of neurological status are similar across studies and include the monitoring of such deficits as hemiparesis, aphasia, nerve palsy, motor deficits and speech disturbances. In most studies the usual standard of practice is to group neurological outcomes into four categories: excellent, good, poor, and death. Excellent is usually defined as a return to preoperative function level with no new neurological deficits. Good is assigned to a patient considered to be ambulatory, cognitively independent but with minor new neurological deficits, and poor is a patient who is dependent or not ambulatory. These categories are often labelled differently; for example as good recovery, mild deficits, severe deficits, and death. They still however represent similar groupings of outcomes. Usually the patients who fall into the poor categories are those represented in morbidity figures. Patients who fall into the good or excellent categories are in turn typically regarded as having had a “favorable” recovery.

Commonly used measures such as the Glasgow Outcome Scale (Jennett & Bond, 1975), the Rankin Scale (Rankin, 1957), or even the Mini-Mental State Examination (Folstein et al., 1975) do not assess cognitive functioning in any detail. It is therefore possible that many people classified as having “favorable” outcome have not returned to their pre-surgery level of functioning (Orz et al., 2000). In addition, many studies reporting morbidity figures do not make explicit their method for classifying deficits or for defining morbidity (King et al., 1994). Finally, use of a single measure of outcome such as neurological status on discharge from hospital, or at 6 weeks post surgery, may also be misleading, especially if the important information is outcome in the long term.

One particularly detailed system of outcome measurement is the scheme proposed by the World Health Organization for the classification of the consequence of any disease (World Health Organization, 1980). As Wade (1996) notes, although considered too complex for everyday use, the WHO model does form a good conceptual framework for understanding neurological deficits. The model notes the need to assess illness on three levels: impairment, disability and handicap. Just recently a new version of the World Health Organization model has been released (World Health Organization, 2001). This revised model defines several domains of health, with these domains grouped under two classifications: (1) body functions and structures; and (2) activities and participation. These two new classifications replace the terms impairment, disability and handicap from the original model, and are said to extend their scope to include positive experiences. In addition, the revised model has moved away from an emphasis on the consequences of disease towards an approach that considers the various components of health (World Health Organization, 2001). Although this revised model undoubtedly builds upon and extends the original model, as it is not yet in widespread use the original model is referred to here.

Impairments are defined as the direct neurophysiological consequences of the underlying pathology (Wade, 1996) and are typically measured by neurological outcome. Assessment of impairment should also include assessment of psychological and neuropsychological dysfunction, such as memory impairment. Disability refers to a disturbance in aspects of a patient's behavior or normal function and is essentially the external, behavioral consequences of the pathology. Examples include slow walking, needing help to dress, no longer being able to cook a simple meal, or forgetting to take one's medication (Wade, 1996). Finally, handicaps are the social and societal consequences of the pathology and are the most important determinant of the severity of the illness from the patient's point of view (Wade, 1996). In essence, handicap reflects the consequences for the individual that stem from the presence of impairment and disability (WHO, 1980). A common example is the patient's inability to return to work full time because of increased fatigue levels (Ogden et al., 1990, 1994). It is this particular aspect of outcome that has in the past been neglected by most morbidity studies of UIAs.

Health-related outcome has many facets, and its measurement should reflect this. As Raaymakers (2000) notes, different measures of outcome may be of differing importance for professionals and patients. A neurosurgeon may be most interested in neurological impairments whereas a patient may consider ongoing quality of life to be the most relevant factor. Behavior is often the most sensitive measure of cerebral function, and hence investigations, including clinical neuropsychological assessments, which assess behavior consistently find problems that are not revealed by other measures of brain function (Kolb & Whishaw, 1996; Lezak, 1995). Neuropsychological assessment can provide data that is useful for both the neurosurgeon and the patient.

A particular difficulty with neurological measures is that common outcome scales may not reveal deficits that can affect people in very debilitating ways. As an example, Ogden et al. (1993) discuss the example of an architect whose work involved a high degree of visuospatial ability. Such an individual would be considerably disadvantaged by very subtle impairments of visuospatial function. However, such deficits are only likely to be detected if comprehensive neuropsychological testing is carried out. As Ogden et al. (1993) note, if the patient is unaware that they have a deficit, even a mild deficit, they may become frustrated and irritable at their work performance. Such emotions may negatively impact on friends, family and colleagues, thereby creating a vicious cycle that ultimately results in a decline in well-being.

Providing patients and their families with simple information about what they can expect with regard to their recovery can help to alleviate many fears and misconceptions and allow patients and families to make the necessary adjustment to their lives. Therefore from the patient's perspective, the neuropsychological report is in many cases likely to be more informative than the neurological report. Neuropsychological assessment is also useful for defining baseline levels of cognitive functioning for longitudinal comparisons with follow-up data. Longitudinal follow-up data is particularly helpful when attempting to identify the rate of improvement or deterioration in cognitive status in response to treatment (Mitrushina et al., 1999). In addition to providing the patient with useful information on their pattern of recovering, neuropsychological data can be used to make inferences at a group level concerning the overall “success” of a particular treatment option.

Neurological status data, such as has been reported in the bulk of the literature on UIA outcome, can also provide useful information regarding the overall impact of a particular treatment option. This is especially pertinent in studies that include large numbers of patients, because of the time-consuming nature of neuropsychological assessment. In addition, when evaluating the effect of a treatment involving neurosurgery, the neurological outcome is clearly important. Therefore, in the early stages of treatment evaluation standard measures of neurological outcome may be most appropriate, with long-term neuropsychological and psychosocial outcome assessed at 3 months, and again at 6 to 12 months following treatment.

To date, very few studies of UIAs have gone beyond the measures of neurological status or simple “screening” tests of cognitive function. There are, however, a few exceptions where researchers have included more comprehensive neuropsychological outcome measures. Fukunaga et al. (1999) recently reviewed the neuropsychological functioning of 30 patients prior to and following surgery for UIAs. Patients who demonstrated a decline in performance 1 month after surgery were tested again 2 months later. The tests used in the study were the Mini Mental State Examination (MMSE), a maze test, and a speeded letter recognition task (“Kana-Hiroi” test). One month after surgery scores on the MMSE decreased in 10 cases, scores on the “Kana-Hiroi” test decreased in 17 cases and the time taken to complete the maze test was increased in 30 cases. All three scores worsened in the case of 6 patients. At 3 months post-surgery all these 6 patients had recovered to pre-operative levels. Patients with anterior communicating artery aneurysms were significantly worse on measures of neuropsychological deterioration following surgery than those with UIAs in other sites.

An interesting finding to emerge from the Fukunaga et al. (1999) study is that residual cognitive deficits remained evident 1 month post surgery but had resolved by the time of the 3-month follow-up assessment. This information can be useful in planning rehabilitation strategies and, as the authors note, for indicating when it is advisable for patients to return to normal life, be this occupationally or socially. However, the Fukunaga et al. (1999) battery covers only a small number of possible cognitive impairments, and therefore their findings are limited in their applicability.

The ISUIA (1988) study also included measures of cognitive change, using the Telephone Interview for Cognitive Status (Brandt et al., 1988) and the MMSE (Folstein et al., 1975). One of the points of interest from this study was the difference in morbidity figures produced by basing outcome on neurological status alone when compared to the morbidity figures derived from basing outcome on cognitive status (2.9% vs. 6.1% at 1 year). Another interesting finding from this study was that of the 90 patients who had either impaired cognitive status or impaired neurological status at one year, only 29 of these had impairments on both measures. Thus the ISUIA (1988) study demonstrates that the assessment of cognitive status detects impairments additional to neurological difficulties and supports the inclusion of both types of outcome measures.

The ISUIA (1988) study has been criticized on several grounds; however only those that relate to the measures of cognitive outcome will be discussed here. First, the study's estimates of cognitive changes were based on a short telephone interview of cognitive status conducted 1 year after surgery. Second, the study also failed to take a measure of pre-operative cognitive functioning, making it difficult to ascertain whether cognitive impairment was due to the intervention or instead reflected pre-morbid variability within the study population (Hillis et al., 2000). In addition, cognitive status was not measured in the patients who did not undergo surgery; therefore there was no comparison group (Alexander & Spetzler, 1999). Despite these difficulties, the ISUIA study takes a positive step with its inclusion of cognitive testing, particularly in such a large sample of patients.

More recently an excellent study of functional outcome and quality of life in 18 patients who underwent elective operation for asymptomatic UIAs was published by Raaymakers (2000). Measures of patient-reported quality of life are considered to be an important component of patient outcome as they give insight into patients' subjective feelings of physical, psychological and social well-being not otherwise detected by measures of functional or cognitive abilities (Hop et al., 1998). Raaymakers (2000) identified the 18 patients who made up the subject pool for the study by screening relatives of patients who had suffered a spontaneous SAH. All patients were assessed in terms of impairments, disabilities, handicaps and quality of life. Disability in activities of daily living were assessed by means of the Barthel Index (Mahoney & Barthel, 1965), handicap by a modified Rankin Scale (Rankin, 1957), and quality of life by the Sickness Impact Profile (SIP) (Bergner et al., 1981) and the Medical Outcomes Study Short Form 36 (Ware & Sherbourne, 1992).

Raaymakers (2000) reported that the combination of angiography and the operation resulted in persistent neurological sequelae in 5 of the 18 patients (28%) if anosmia was included as a neurological deficit, and 3 of the 18 patients (17%) if it was not, with these sequelae present at three months and one year after the operation. In terms of other measures of outcome, 3 months after surgery 2 patients had disabilities, as measured by the Barthel Index and 15 had less than optimal Rankin handicap scores. At 1 year after operation all disabilities had resolved. However, 8 patients still had sub-optimal Rankin handicap scores. In terms of the quality of life findings, Raaymakers (2000) reports that according to the SIP at 3 months, 16 patients had a lower quality of life than before their operation, and according to the SF-36, 11 patients showed a decrease in quality of life. At 1 year, according to the SIP 10 patients still reported a decrease in quality of life whereas on the SF-36 8 patients reported a decrease in quality of life. Raaymakers (2000) concluded that elective surgery for unruptured aneurysm has a short-term negative impact on quality of life in most patients. However, 1 year after operation, outcome had considerably improved, although recovery was not complete. Raaymakers (2000) noted that these results could only be generalized to patients with incidentally found, mostly small aneurysms, who have one relative with SAH. Whether these same outcomes also apply to other categories of patients treated for unruptured aneurysms is not known.

Hillis et al. (2000) have also recently published a study of cognitive impairments following surgery for UIAs. In addition to being valuable for its analysis of cognitive functioning following treatment for UIAs, the study is also notable because it conducts pre-surgery and post-surgery testing. Such testing allows patients' performances following treatment to be evaluated against their own pre-operative performance level.

This is a more reliable method than comparing post-treatment performance to published test norms to assess outcome. In the Hillis et al. (2000) study, a subset of 12 patients were administered a comprehensive battery of neuropsychological tests prior to surgery and approximately 3 months after surgery. As a group, poorer post-operative performance was reported on tests of verbal fluency, immediate and delayed verbal recall, and “frontal lobe” or executive abilities. The authors comment that as impairments in these areas are also commonly found to follow repair of ruptured aneurysms, a proportion of the long-term cognitive sequelae of SAH may result from the effects of the neurosurgery per se, rather than from the hemorrhage. This study does suffer from small patient numbers, and a 3-month follow-up time is quite short for assessment of neuropsychological function. It is possible that many of the impairments may have resolved given a longer follow-up period and that deficits may have been underestimated due to possible test-retest effects given such a short follow-up period.

In addition to the possibility of cognitive changes or quality of life deterioration following UIA treatment, it is also necessary to consider the costs of not having the aneurysm treated, and carrying the ongoing risk of the aneurysm rupturing at any point in time. In their study on the costs and benefits of treating UIAs Johnston et al. (1999b) estimated that the cost of living with a low risk, but high consequence, condition would produce a mildly impaired emotional state (Johnston et al., 1999b). As the risks associated with the aneurysm increased, or the UIA produced painful or compressive symptoms, the emotional costs of living with the untreated aneurysm increased. The ongoing emotional disturbance associated with living with an untreated UIA is an important variable to take into consideration when evaluating treatment options, but it is at this stage largely unmeasured.

Neuropsychological and Psychosocial Assessment: Future Recommendations

Although the few neuropsychological and psychosocial outcome studies published make an excellent contribution and their preliminary findings are an important step forward, further comprehensive studies are needed. Some recommendations of how these studies might be conducted follow.