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Background:
Neuropsychological deficits (NPD) are a common finding in patients with aneurysmal subarachnoid haemorrhage (aSAH). NPD are one of the major limiting factors for patients with an otherwise good outcome to continue a pre-morbid way of life. Traditional outcome measures such as the Glasgow Outcome Scale (GOS) or the modified Rankin Scale (mRS) do not correlate with or predict NPD. Therefore, a modern outcome evaluation after aSAH should include the assessment of health-related quality of life (HRQoL) and NPD. Despite the fact that the majority of highly specialized neurovascular and neurorehabilitation centres dealing with aSAH patients rely on professional neuropsychological testing as a sensitive tool to detect possible therapeutic targets during rehabilitation, only few high quality studies published recently have used a standardized cognitive testing battery as a primary or secondary outcome measure.

Objective
The aim of this study was to assess the current practice of neuropsychological outcome reporting after aSAH using a MEDLINE analysis. Moreover, possible reasons for the low acceptance of neuropsychological testing in clinical trials are discussed.

Methods
A MEDLINE analysis was performed on November 26, 2012, using the search term “subarachnoid hemorrhage outcome”. Of the search results, the latest 1000 articles were analyzed. Only peer-reviewed English-language studies on human subjects reporting clinical outcome after aSAH including either mortality, neurological, HRQoL or neuropsychological outcome scales were considered. Animal studies or experimental articles solely reporting laboratory (e.g., inflammatory markers), physiologic (e.g., blood pressure) or radiological (e.g., vessel diameter on CT angiography) end points were not included. Furthermore, review articles, meta-analyses, case reports, and case series with ≤ 3 patients were also excluded. Captured parameters were the study design (prospective randomized trial, PRT; prospective observational study, and retrospective cohort study), the number of patients, and the existence of a neuropsychological outcome report. Studies reporting neuropsychological outcome were subsequently analyzed in detail. Here, the time of testing after aSAH, the neuropsychological tests used, as well as the percentage of patients with NPD were analyzed.

Results
- 324 articles on 346,666 patients published between 2009 and 2012 were reviewed
- 21/324 articles (6.48%) reported neuropsychological outcome
- in 2,001/346,666 of study patients (0.58%) neuropsychological outcome was assessed
- 18/96 prospective studies (18.75%), 3/206 retrospective studies (1.46%), and no PRT included neuropsychological outcome measures
- the studies using neuropsychological outcome measures differed broadly with regard to time after onset of aSAH, the neuropsychological domains tested, the neuropsychological tests used
- the cohort being tested (frequently patients with less favorable clinical outcomes were excluded)
- in 17/21 studies the neuropsychological evaluation was performed by a professional using a face-to-face interview and standardized tests
- the incidence of NPD thus ranged between 19.2 - 73% at 3 months and between 21 - 100% at 12 months following aSAH
- it was almost impossible to compare the results of the different studies

Discussion
There must be reasons for this unfavorable status quo:
1) From the physician’s perspective, there is a high organizational and financial burden associated with implementation of comprehensive neuropsychological assessments in a prospective multicenter project.
2) Especially in aSAH patients with poor-grade outcome and limited attention span, a highly demanding neuropsychological assessment requires a supreme effort of the patient. This can make the application of a standardized protocol impossible.
3) A myriad of neuropsychological tests exist to assess various cognitive domains in humans and normative data are not always available for different languages, genders, or educational status. International multicenter studies struggle with a lack of comparability.

Conclusion
Neuropsychological outcome after aSAH is underreported and its assessment shows great variety in currently published clinical series. There is a need for a comprehensive and validated testing battery that could serve as basis for studies on this subject to enable comparison of results. Future PRTs for aSAH management may benefit from neuropsychological outcome evaluation. This approach might identify otherwise unnoticed treatment effects in future intervention studies, even when no influence on the mRS or GOS is evident.

Conflict of interest / funding:
The authors declare no conflicts of interest. There was no funding received for this study.