The PubMed search identified 743 articles; 109 duplicates were removed, resulting in 634 potentially relevant citations (see ESM 1). Following the screening of titles, abstracts and entire articles, a total of 28 articles were retained for inclusion in this systematic review (Fig. 1).
Eight reports were of national populations (Austria, Finland, Germany [2×], Norway, Scotland, Spain and Netherlands). One study compared the epidemiology of TBI between regions of different European countries . Nineteen focused on regions, counties or provinces of one European country. Altogether we found data from sixteen different countries: Norway, Sweden, Netherlands, Italy, Germany, Greece, Finland, France, Austria, Slovak Republic, Croatia, Macedonia, Bosnia, Poland and Scotland.
Fifteen out of the 28 studies had a study period of exactly 1 year, five studies [14, 18, 25, 33, 35] had a study period of 10 years or more. The number of included patients ranged from 247  to 280,000 , the size of the total source population from 83,900  to 82,037,100 . Nine studies did not report their source population size. Characteristics of the included studies and results of quality assessment are presented in Table 1.
Methodological quality and incidence
A total of 19 studies met the five selected STROBE criteria. Nine studies did not meet all five criteria, of which two failed on two criteria and a further 2 on three criteria (Table 1). Table 2 summarises details of inclusion criteria, case definitions, severity assessment and reported/calculated incidence rates per year of the selected studies. A large variation was found in inclusion criteria, case ascertainment and case definitions. Eight studies were based on hospital admissions, six on emergency department admissions and four on a combination of both. Other sources used for case ascertainment were death certificates, ICU admissions, hospital discharges, pre-hospital emergencies, or a combination of these. We also found large differences in the case criteria that were used in the studies. Seven studies used ICD-10 codes to define TBI, seven used ICD-9 codes and another two used both. Five studies used the GCS. Other tools that were used to define TBI, were Head Injury Severity Scale (HISS), Abbreviated Injury Scale (AIS) or clinical symptoms. Twenty-one out of 28 studies provided information on the severity distribution of TBI. The severity of TBI was measured by the GCS score in 12 out of these 21 studies. Other methods that have been used to measure the TBI severity were AIS head score, HISS score, or ICD codes. Eight out of 21 studies focused on severe or moderate-to-severe TBIs. In studies that provide complete information on all TBI severities (n = 12; [2, 3, 5, 7, 10, 12, 24, 27, 31, 34, 36, 37]), we see that the percentage of mild TBIs varies between 71 %  and 97.5 % .
These differences make it difficult to compare the incidence. Six out of 28 studies did not report an incidence rate. Out of the remaining 22 studies, five focused on severe or moderate-to-severe TBI [1, 18–20, 26]. The other 17 studies focused on patients with all TBI severities. The incidences of these 17 studies displayed a large variation: Pérez et al. (2011)  reported an incidence rate of 47.3 per 105 population per year in Spain in 2000–2009, while Andersson et al. (2003)  reported a rate of 546 per 105 population per year in Western Sweden in 1992–1993. Including only the studies that focus on patients with severe TBI (n = 4), a range of incidence is reported from 4.1 per 105 population in Norway  to 17.3 per 105 population in Aquitaine, France . Fig. 2 illustrates this wide variation of reported incidence rates. We note that studies concentrating on severe TBI [1, 18–20] cluster to the left (low incidence) and those including all injuries to the right (higher incidence).
A meta-analysis of the 17 studies focusing on patients with all TBI severities was performed. Figure 3 shows the large variation of these incidences and a substantial degree of heterogeneity was confirmed on statistical evaluation (I
2 = 99.9 %; Z = 6.687). An overall incidence rate of 262 (CI, 185–339) per 100,000 per year for admitted TBI patients was derived.
Epidemiological patterns: age, sex and cause of TBI
Table 3 presents demographic data of the study populations. In assessing the age distribution, we must note that some studies only include adults in their study population. With this caveat in mind, we see that, in general, TBI is more prevalent among people aged <25 years and among people >75 years. In three studies [14, 18, 26] an increase is seen in the elderly percentile or the mean age over the years of the study.
Mean age varies strongly: Styrke et al. (2007)  reported a mean age of 22 years, while Mauritz et al. (2008)  reported a mean age of 49 years. The latter study, however, included only severe TBI cases. The variation in mean age probably reflects different case ascertainment and inclusion criteria. In most cases, the mean age in females was higher than the mean age in males.
In all 28 studies, there was a male predominance: the male-to-female ratio ranged from 1.2:1.0  to 4.6:1.0 .
In 13 out of 26 studies that provided data on the mechanisms of injury, falls were the most frequent cause of TBI. Road traffic accidents (RTAs) were reported as the most frequent cause of TBI in 11 studies. Table 4 shows the most frequent causes of TBI in the study period and TBI severity. In 8 out of 13 studies that include data from before 2000, RTAs are reported as the main cause of TBI. Falls were dominant in the remaining five studies. Only 2 out of 12 studies that include solely data from 2000 or later report RTA as the main cause of the brain injury. In eight studies, falls were dominant. Thus, over time a clear shift can be seen in terms of leading cause of TBI, namely from RTAs to falls.
Within the studies that focus mainly on more severe TBI, RTA as a cause of injury remains dominant. In this category of studies (moderate-to-severe and severe TBI only), RTA remains the leading cause in six out of eight studies.
A clear correlation was also found between age and mechanism of injury. Falls are most common in two age groups: the elderly and children. In contrast, RTAs are the most frequent cause in the age group of young adults. Also notable is the geographical spread of the mechanisms of injury: Scandinavian countries reported mainly falls, while other countries reported more RTAs.
Mortality rate and case fatality rate
Nine studies reported data on mortality rates (ESM 2). As with the incidence rates, a large variation was found in the mortality rates: from 3.0 per 105 inhabitants per year in Hannover and Münster (Germany)  to 18.3 per 105 inhabitants per year in Finland and Romagna (Italy) [14, 31]. This variation can largely be explained by differences in case ascertainment and case definitions. Overall, an average mortality rate of 10.5/100,000 was calculated, but interpretation should be with caution due to the heterogeneity of studies.
The case fatality rate (CFR) expresses disease-specific mortality (e.g. TBI). However, the specificity of the rate is influenced by the inclusion of patients who have died from systemic injuries or non-brain comorbidity. Distinction is made between in-hospital CFR (only in-hospital deaths) and overall CFR (in-hospital and out-of-hospital deaths). CFR is highly dependent on the severity of TBI and age of TBI patients: CFR of TBI in general ranges from 0.9 per 100 patients to 7.6 per 100 patients, while CFR of severe TBI ranges from 29 to 55 per 100 patients. None of the included studies provide information on the difference between CFR in mild TBI compared to severe TBI.