DÄ internationalArchive12/2010Clinical Findings in the Chronic Phase of Traumatic Brain Injury

Original article

Clinical Findings in the Chronic Phase of Traumatic Brain Injury

Data From 12 Years’ Experience in the Cognitive Neurology Outpatient Clinic at the University of Leipzig

Dtsch Arztebl Int 2010; 107(12): 199-205. DOI: 10.3238/arztebl.2010.0199

Scheid, R; Cramon, D Y v

Back­ground: There are many unre­solved issues in the diagnosis and treat­ment of persons with trau­matic brain injury (TBI) in its post-acute and chronic phases. This article deals with two problems of clinical import­ance: (i) the inter­re­la­ti­ons­hips between struc­tural brain damage, brain func­tion, and clinical outcome, and (ii) post-trau­matic epilepsy.
Methods: Explo­ra­tory, retro­spec­tive analysis of clinical, neuro­ra­dio­lo­gical (MRI), and neuro­psy­cho­lo­gical data of all pati­ents with TBI who were treated in a cogni­tive neuro­logy outpa­tient clinic of a German univer­sity hospital over a period of 12 years (n=320).
Results: 156 pati­ents (48.8%) had brain contu­sions, 83 of them (25.9%) as the sole neuro­ra­dio­lo­gical abnor­ma­lity. Trau­matic micro-hemor­r­hages were seen in 148 pati­ents (46.2%) and were the sole neuro­ra­dio­lo­gical abnor­ma­lity in 79 of them (24.7%). 49 pati­ents (15.3%) had no struc­tural brain lesion. There was no obvious corre­la­tion between the neuro­ra­dio­lo­gical findings and the clinical outcome, as measured either by a general outcome para­meter such as the extended Glasgow Outcome Scale (GOSE) or by neuro­psy­cho­lo­gical testing.
47 pati­ents (14.7 %) had post-trau­matic epilepsy; its occur­rence was posi­tively corre­lated with the presence of brain contu­sions, but not with an isolated diagnosis of diffuse axonal injury (DAI).
Conclu­sion: A compa­rison of the findings of neuro­ra­dio­lo­gical studies and neuro­psy­cho­lo­gical tests among pati­ents in the chronic phase of trau­matic brain injury does not reveal any simple rela­ti­onship between struc­tural and func­tional brain abnor­ma­li­ties. Diffuse axonal injury is often present in combi­na­tion with other findings, and it may well be the only struc­tural abnor­ma­lity in many cases; there­fore, all sympto­matic pati­ents should undergo MRI of the brain. Pati­ents with isolated DAI seem to be less prone to post-trau­matic epilepsy than those with brain contu­sions.
LNSLNS Traumatic brain injury (TBI) is one of the commonest disorders within neuropsychiatry in its widest sense. The incidence of TBI in Germany is approximately 332 per 100 000, in comparison to 182 per 100 000 for strokes (1, 2). Its annual direct and indirect costs amount to roughly 2.5 billion euros (2). It is generally accepted that its overall burden for health economics is equal to the total costs of other well-known neurological diseases such as Parkinson’s disease, multiple sclerosis, Guillain-Barré syndrome, amyotrophic lateral sclerosis, and myasthenia combined (3). However, despite an overabundance of literature—the PubMed database has more than 50 000 hits for the search term “traumatic brain injury”—the complex area of TBI is actually somewhat overlooked in both medical training and subsequent general medical and neuropsychiatric practice.

There are many questions regarding the diagnosis, prognosis and best possible treatment of traumatic brain injury in its post-acute and chronic phases that cannot yet be satisfactorily answered. This article focuses mainly on the clinically significant aspects of potential interrelationships between structural brain damage, brain function, and clinical outcome, and on the frequency and conditions for onset of post-traumatic epilepsy. It is based on an exploratory, retrospective analysis of the clinical data of all TBI patients of the Cognitive Neurology Outpatient Clinic at the University of Leipzig, Germany from 1996 to 2007. The overwhelming majority (>85%) of the neuroradiological information provided is derived from MRI data. Until now this type of evaluation, based on MRI data alone, has not been standard for this patient population in either clinical practice or larger clinical studies. It therefore deserves particular mention.

The descriptive findings are discussed in the context of searches of the literature. The research makes a contribution to the diagnosis and interpretation of morphological/structural and functional consequences of traumatic brain lesions. Ideally, this should also stimulate a process at the end of which this potentially chronic and serious brain damage is given the professional attention which it deserves on the strength of epidemiological data.

Methods
Database and data collection
Between January 1, 1996 and December 31, 2007 (the last day covered by this evaluation), 320 patients (18%) with a primary diagnosis of TBI (the inclusion criterion) were treated in the Cognitive Neurology Outpatient Clinic at the University of Leipzig. For this retrospective analysis, the following data on these patients were taken from electronic and original medical records:

• Sex
• Age on the dates of the injury and magnetic resonance imaging (MRI)
• Closed or open TBI
• Glasgow Coma Scale (GCS) score (according to ER records or, if these do not exist or are not available, calculated retrospectively for the patient’s condition at the site of the accident when attended by a professional paramedic) (e1, e2)
• Previous illnesses
• Medications taken at the time of the injury
• Cause of TBI
• Presence of polytrauma, skull fracture, generalized brain edema, or hypoxic encephalopathy.
• The following injury patterns were recorded:
• Subarachnoid hemorrhages (SAHs)
• Subdural hemorrhages (SDHs)
• Epidural hemorrhages (EDHs)
• Hygromata
• Contusions and their locations
• Traumatic microbleeds (TMBs) and their locations as a marker of diffuse axonal injury (DAI)
• Diffuse vascular injury (DVI) or traumatic intracerebral hematomas (9)
• Midbrain and/or brainstem injuries
• Injuries to blood vessels that supply the brain.

Patient subgroups had already been included in several individual studies, particularly regarding potential structural and functional correlates of DAI (48).

The following were recorded as the functional and clinical outcome parameters at the time of patients’ semi-inpatient hospital stays (median 12 months post-trauma):

• Results of standardized neuropsychological testing
• Extended Glasgow Outcome Scale (GOSE) score (e3)
• Post-traumatic epilepsy
• Psychiatric morbidity (according to ICD-10 criteria wherever possible)
• Ongoing prescription of psychoactive drugs.

MRI
274 patients (86%) underwent at least one brain MRI scan after having the procedure explained to them and after consenting to it. There were contraindications for MRI in 46 patients. The scans were performed using two 3-Tesla whole-body scanners (for information on machine specifications and scan protocols, see [4, 5]).

Neuropsychological examinations
All patients underwent neuropsychological examination of attention and psychomotor speed (e4), executive functions (e5, e6), learning/memory (e7, e8), and intelligence (e9). Where there were results for more than one point in time, those from the patients’ first stay at the clinic were used for this evaluation.

Statistical calculations
The data gathered were statistically tested for any significant correlations between clinical variables (Fisher’s exact test, Mann-Whitney U test, Spearman’s rank correlation). Unless explicitly stated otherwise, the enquiry in each case was exploratory, and significance levels are therefore not given. One exception to this is the hypothesis-led enquiry into statistically significant correlations between structural findings and the results of neuropsychological tests (Mann-Whitney U test, Spearman’s rank correlation). Specifically, the patients’ results in the following neuropsychological tests were used as parameters:

• TAP (Test for Attentional Performance) test battery (e4)
• Behavioral Assessment of the Dysexecutive Syndrome (BADS) (e5)
• Stroop test (e6)
• California Verbal Learning Test (CVLT) (e7)
• Wechsler Memory Scale—Revised (WMS-R) (e8)
• Multiple-Choice Vocabulary Intelligence Test (MWT A/B) (e9).

Altogether, confirmation of 22 hypotheses was sought (multiple significance level = 0.05; local significance level following correction for multiple testing [Bonferroni correction] = 0.0023). All statistical calculations were carried out using SPSS software, version 15.
Results
Clinical histories
Table 1 (gif ppt) provides an overview of patient demographics. Road traffic accidents (RTAs) were the leading cause of TBI, accounting for 69% of cases (221 patients). Next came falls, with 25.6% (82 patients); and blows to the head, with 5% (16 patients). In one patient (0.3%), brain injury was caused by a blow and a fall combined. Within the RTA group, car accidents (43.4%, 139 patients) were the leading cause, followed by bicycle/motorcycle accidents (20.6%, 66 patients) and pedestrians involved in RTAs (5%, 16 patients).

Structural findings
156 patients (48.8%) had brain contusions, 83 of them (25.9%) as the sole neuroradiological abnormality, i.e. there were no other traumatic parenchymatous changes (Figure 1 gif ppt and Table 2 gif ppt). Traumatic microbleeds were seen in 148 patients (46.2%) and were the sole neuroradiological abnormality in 79 of them (24.7%) (Figure 1 and Table 2). Significant generalized brain atrophy according to visual criteria was observed in 13 patients (4%). As no quantitative analyses were carried out regarding this, no statistical calculations were performed. However, 12 of these patients showed clear signs of traumatic microbleeds. 27 patients (8.4%) had isolated extra-axial injuries. In 49 patients (15.3%), no structural consequences of trauma were detectable on imaging at any time. Thus, examination of patients with isolated extra-axial injury included, imaging revealed no chronic morphological parenchymatous traumatic signal changes in a total of 76 patients (23.8%).

Clinical condition
On the GOSE, 18 patients (5.6%) achieved a score of 4, 74 patients (23.1%) a score of 5, 124 patients (38.8%) a score of 6, 88 patients (27.5%) a score of 7, and 9 patients (2.8%) the highest score, 8; the median of the sample was 6. For 7 patients (2.2%), there were not enough data for sufficiently accurate calculation. There was a weak correlation between severity of initial TBI according to the GCS and outcome according to the GOSE (Spearman’s rank correlation [rs] = 0.335, p<0.001).

There were also statistical correlations both between GCS/GOSE and evidence of a structural brain lesion in general (p<0.001/ p = 0.006, Mann-Whitney U test), and between GCS/GOSE and evidence of substantial cranial trauma (patients with extra-axial injury patterns but no parenchymatous lesions) (p<0.001/p = 0.007, Mann-Whitney U test). There was also evidence of statistical correlations between GCS/GOSE and history of brain edema during the acute phase (p<0.001/p = 0.008, Mann-Whitney U test). Finally, there were correlations between the GCS and primary presence of contusions/traumatic microbleeds (p = 0.004/p = 0.005, Mann-Whitney U test) but not between evidence of contusions/traumatic microbleeds as the primary or sole neuroradiological abnormality and GOSE scores (contusions: p = 0.051 and p = 0.228; traumatic microbleeds: p = 0.244 and p = 0.467, Mann-Whitney U test).

Correlations between imaging, clinical, and neuropsychological findings
Contrary to the hypothetical assumption, there was no correlation between GCS/GOSE and neuropsychological test results (Spearman’s rank correlation, multiple significance level p = 0.05, local significance level p = 0.0023), nor was any statistically significant correlation found between the latter and the following parameters (Mann-Whitney U test, p>0.0023 in each case):

• Traumatic microbleeds (general or isolated)
• Contusions (general or isolated)
• Other traumatic parenchymatous brain lesions
• Corpus callosum, midbrain, or brainstem lesions
• Generalized brain edema during the acute phase.

Post-traumatic epilepsy
47 patients (14.7%) suffered post-traumatic epilepsy. Onset was not correlated with TBI severity according to the GCS (p = 0.739, Mann-Whitney U test), but it was negatively correlated with outcome according to the GOSE (p = 0.048, Mann-Whitney U test). Post-traumatic epilepsy occurred with detectable contusions in 20% of patients. In contrast, only 10% of patients with traumatic microbleeds were affected. There was a statistical correlation between post-traumatic epilepsy and isolated contusions (p<0.001, Fisher’s exact test), but not between the former and isolated traumatic microbleeds (p = 0.713, Fisher’s exact test).

Discussion
Types and causes of traumatic brain lesions
The findings on the type, frequency, pattern, and mechanism of traumatic brain damage partly confirm the results stated in the literature (2, 911). This is particularly true, for example, for the distribution of contusional injuries, which tend to affect the structures of the frontal pole/front base and temporal pole (9, 10). Discrepancies from the conclusions of current large epidemiological studies (2), such as those on the cause and severity of TBI, may be dependent on various different factors. Worthy of particular mention are the retrospective nature of data collection and the fact that all the information on the patient population was obtained from a single clinic which focuses mainly on cognitive rehabilitation. This latter fact undoubtedly results in selection bias. Despite this limitation, however, the evaluation does yield well-founded information on the range of structural and functional findings from a sample of patients suffering from chronic problems as a result of TBI. It is therefore suitable for use as a source of data, including for comparative investigations of other establishments.

The results of the research show that traumatic microbleeds are present in around half of cases, either alone or with contusions. If we consider these changes to be neuroradiological markers of DAI (4), this means that “pure DAI” is present in around half of cases. This has direct consequences for imaging diagnostics: all symptomatic TBI patients should undergo MRI examination (Figure 2 gif ppt). Particularly suitable sequences in this context are currently T2*-weighted gradient-echo imaging (T2*GRE), susceptibility-weighted imaging (SWI), and diffusion tensor imaging (DTI) (4, 14, 15).

Lack of evidence of traumatic brain damage
Patients in whom no structural brain damage is evident and patients with no definite evidence of substantial TBI (i.e. also with no isolated extra-axial injury) combined represent the category “minor head injury” (12, e10, e11). There were significant correlations to both the GCS and the GOSE for both groups. The relatively high proportion, almost a quarter (23.8%), of patients who fell into these two categories is emphatic evidence of the significance of this problem. It also makes it clear that some patients suffer from chronic health disorders (general, neurological, cognitive, or psychological) comprising “post-concussion syndrome” even after mild TBI (12, 13, e10). After all, these sequelae were sufficiently pronounced for an outpatient clinic to be attended and/or for the attention of primary care physicians, neurologists/neuropsychiatrists, or inpatient rehabilitation establishments to be considered necessary. The causes and conditions for onset of such disorders are hotly disputed (e10, e12). Conventional neuroradiological procedures have not proved helpful to date (14, e13, e14). Further efforts regarding objective evidence of potential underlying neuronal damage (15) are therefore necessary and worthwhile, with respect to both diagnostic and therapeutic issues and medical law.

Neuropsychological data and magnetic resonance imaging
No conclusive relationship to structural injury patterns has been found using either the GOSE or neuropsychological tests. This comes in addition to equivalent results of a separate study involving patients with isolated traumatic microbleeds (5). It is true that varying profiles of patients with focal and diffuse damage patterns were described by Wallesch et al. according to the relevant clinical scales (Neurobehavioral Rating Scale, Frontal Lobe Score) (16, e15) and that these point to varying disorders, mainly in the frontal-subcortical neuronal circuits in the context of contusional and DAI-compatible injuries as functional neuroanatomical causes. However, in general, focal and diffuse injuries combined probably contribute to general and neuropsychological outcomes, and in this case neuropsychological tests are of only limited use in distinguishing between these different injury patterns (17).

Many studies of TBI involving neuropsychological data yield inconsistent findings on structural or functional correlations (5, 1619, e14, e16). Regarding etiology, it must be borne in mind that TBI is heterogeneous and consists of different dynamic processes at different times of assessment, and that these processes are also affected by often multiple neuropsychiatric (co-)morbidities (20). There are also multiple suspected adaptive and neuroplastic processes about whose conditions, progress, and efficacy current knowledge is still rudimentary (e17). Interestingly, our results are also in line with the evaluation of a current long-term psychiatric observation. This long-term observation concludes that most post-traumatic psychiatric disorders on Axes I and II according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) have only a very limited relationship to outcome and the specific location of cortical contusions (Axis I: Major clinical disorders including developmental and learning disabilities; Axis II: personality disorders, mental retardation) (21).

Post-traumatic epilepsy
TBI is a major cause of epileptic fits (22). Approximately 15% of patients suffered from post-traumatic epilepsy. This figure is higher than generally assumed (4% to 7%) (e18, e19) but roughly corresponds to the observed incidence of approximately 17% in TBI patients with non-penetrating injuries in rehabilitation establishments (e20).

Contusions have been established as a risk factor (e21, e22). A corresponding correlation was also found in our patients. Worthy of note is the low prevalence of post-traumatic seizures in patients with isolated traumatic microbleeds. It could be deduced from this that patients with “pure DAI” are at lower risk. There are no systematic findings on this in the literature. This is not a trivial observation, as intra-cerebral hemorrhages are generally associated with the opposite: a higher risk of seizures (23, e20). A possible explanation for this may be the extracortical location of the majority of the associated changes. However, in most cases of epilepsy with “subclinical cerebrovascular disorders,” for example, the cerebellar white matter is also primarily affected (24, 25, e23), and such disorders are also associated with the onset of cerebral micro-hemorrhages (e24). Regardless of the possible pathogenesis, the finding should nevertheless be verified by further research, as it may be prognostically relevant.

The literature provides no completely consistent information on the relationship between post-traumatic seizures and clinical outcome in the literature (e20). The evidence found here of an inverse correlation with the GOSE supports the assumption that post-traumatic epilepsy, unlike post-traumatic early seizures, has a negative effect on general functional outcome as a result of the other health-related, psychological, and potentially work-related consequences associated with it.

Acknowledgement
The authors would like to thank the patients and in particular all the staff at the Cognitive Neurology Outpatient Clinic at the University of Leipzig, Germany, without whose help and ongoing dedication this article could not have been written.

Conflict of interest statement
The authors declare that no conflict of interest exists according to the guidelines of the International Committee of Medical Journal Editors.

Manuscript submitted on 23 January 2009, revised version accepted on 3 September 2009.

Translated from the original German by Caroline Devitt, MA.


Corresponding author
PD Dr. med. habil. Rainer Scheid
Max-Planck-Institut für Kognitions- und Neurowissenschaften
Stephanstr. 1A
04103 Leipzig, Germany
scheid@cbs.mpg.de


@For e-references please refer to:
www.aerzteblatt-international.de/ref1210
2.
Rickels E, von Wild K, Wenzlaff P, Bock WJ: Schädel-Hirn-Verletzung. Epidemiologie und Versorgung – Ergebnisse einer prospektiven Studie. München: W. Zuckschwerdt Verlag 2006.
3.
Kiraly M, Kiraly SJ: Traumatic brain injury and delayed sequelae: a review—traumatic brain injury and mild traumatic brain injury (concussion) are precursors to later-onset brain disorders, including early-onset dementia. Sci World J 2007; 12: 1768–76. MEDLINE
4.
Scheid R, Preul C, Gruber O, Wiggins C, von Cramon DY: Diffuse axonal injury associated with chronic traumatic brain injury: Evidence from T2*-weighted gradient-echo imaging at 3 T. AJNR Am J Neuroradiol 2003; 24: 1049–56. MEDLINE
5.
Scheid R, Walther K, Guthke T, Preul C, von Cramon DY: Cognitive sequelae of diffuse axonal injury. Arch Neurol 2006; 63: 418–24. MEDLINE
6.
Scheid R, Zimmer C, Schroeter ML, Ballaschke O, von Cramon DY: The clinical spectrum of blunt cerebrovascular injury. Neurologist 2006; 12: 255–62. MEDLINE
7.
Scheid R, Ott DV, Roth H, Schroeter ML, von Cramon DY: Comparative MR-imaging at 1.5 T and 3 T for the evaluation of traumatic microbleeds. J Neurotrauma 2007; 24: 1811–6. MEDLINE
8.
Schroeter ML, Ettrich B, Schwier BS, Scheid R, Guthke T, von Cramon DY: Diffuse axonal injury due to traumatic brain injury alters inhibition of imitative response tendencies. Neuropsychologia 2007; 45: 3149–56. MEDLINE
9.
Graham DI, Gennarelli TA, McIntosh TA: Trauma. In: Graham DI, Lantos PI (eds.): Greenfield’s neuropathology. 7th ed. London, New York: Arnold 2002: 823–98.
10.
Bigler ED: Neuroimaging correlates of functional outcome. In: Zasler ND, Katz DI, Zafonte RD (eds.): Brain injury medicine: principles and practice. New York: Demos Medical Publishing; 2007: 201–24.
11.
Brown AW, Elovic EP, Kothari S, Flanagan SR, Kwasnica C: Congenital and acquired brain injury. 1. Epidemiology, pathophysiology, prognostication, innovative treatments, and prevention. Arch Phys Med Rehabil 2008; 89(Suppl 1): p.3–p.8. MEDLINE
12.
Ropper AH, Gorson KC: Concussion. N Engl J Med 2007; 356: 166–72. MEDLINE
13.
Deb S, Lyons I, Koutzoukis C: Neurosychiatric sequelae one year after minor head injury. J Neurol Neurosurg Psychiatry 1998; 65: 899–902. MEDLINE
14.
Metting Z, Rödiger LA, De Keyser J, van der Naalt J: Structural and functional neuroimaging in mild-to-moderate head injury. Lancet Neurol 2007; 6: 699–710. MEDLINE
15.
Niogi SN, Mukherjee P, Ghajar J, et al.: Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury. AJNR Am J Neuroradiol 2008; 29: 967–73. MEDLINE
16.
Wallesch CW, Curio N, Kutz S, Jost S, Bartels C, Synowitz H: Outcome after mild-to-moderate blunt head injury: effects of focal lesions and diffuse axonal injury. Brain Injury 2001; 15: 401–12. MEDLINE
17.
Wilson JT, Hadley DM, Wiedmann KD, Teasdale GM: Neuropsychological consequences of two patterns of brain damage shown by MRI in survivors of severe head injury. J Neurol Neurosurg Psychiatry 1995; 59: 328–31. MEDLINE
18.
Felmingham KL, Baguley IJ, Green AM: Effects of diffuse axonal injury on speed of information processing following severe traumatic brain injury. Neuropsychol 2004; 18: 564–71. MEDLINE
19.
Fork M, Bartels C, Ebert AD, Grubich C, Synowitz H, Wallesch CW: Neuropsychological sequelae of diffuse traumatic brain injury. Brain Injury 2005; 19: 101–8. MEDLINE
20.
McAllister TW: Neuropsychiatric aspects of TBI. In: Zasler ND, Katz DI, Zafonte RD (eds.): Brain injury medicine: principles and practice. New York: Demos Medical Publishing; 2007: 835–61.
21.
Koponen S, Taiminen T, Kurki T, et al.: MRI findings and Axis I and II psychiatric disorders after traumatic brain injury: a 30-year retrospective follow-up study. Psychiatry Res 2006; 146: 263–70. MEDLINE
22.
Christensen J, Pedersen MG, Pedersen CB, Sidenius P, Olsen J, Vestergaard M: Long-term risk of epilepsy after traumatic brain injury in children and young adults: a population-based cohort study. Lancet 2009; 373: 1105–10. MEDLINE
23.
Temkin NR: Risk factors for post-traumatic seizures. Epilepsia 2003; 44(Suppl 10): 18–20. MEDLINE
24.
Duncan JS, Sander JW, Sisodiya SM, Walker MC: Adult epilepsy. Lancet 2006; 367: 1087–100. MEDLINE
25.
Werhan KJ: Epilepsy in the Elderly [Altersepilepsie]. Dtsch Arztebl Int 2009; 106(9): 135–42. VOLLTEXT
e1.
Teasdale G, Jennett B: Assessment of coma and impaired consciousness. A practical scale. Lancet 1974; 2: 81–4. MEDLINE
e2.
Katz DI, Alexander MP: Traumatic brain injury. Predicting course of recovery and outcome for patients admitted to rehabilitation. Arch Neurol 1994; 51: 661–70. MEDLINE
e3.
Wilson JT, Pettigrew LE, Teasdale GM: Structured interviews for the Glasgow Outcome Scale and the Extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma 1998; 15: 573–85. MEDLINE
e4.
Zimmermann P, Fimm B: Testbatterie zur Aufmerksamkeitsprüfung (TAP). [Test battery for the assessment of attention]. Psychologische Testsysteme. Würselen; 1993.
e5.
Wilson B, Alderman N, Burgess PW, Emslie H, Evans JJ: Behavioural assessment of the dysexecutive syndrome. Thames Valley Test Company. Bury St. Edmunds; 1996.
e6.
Wolfram H, Neumann J, Wieczorek V: Psychologische Leistungstests in der Neurologie und Psychiatrie. [Psychological performance test in neurology and psychiatry]. VEB Georg Thieme. Leipzig; 1986.
e7.
Delis DC, Kramer JH, Kaplan E, Obler BA: The California verbal learning test: Adult version. The Psychological Corporation. San Antonio; 1987.
e8.
Härting C, Markowitsch HJ, Neufeld U, Calabrese P, Deisinger K, Kessler J: Wechsler Gedächtnis Test – Revidierte Fassung (WMS-R). [German version of the revised version of the Wechsler memory scale]. Bern: Verlag Hans Huber 2000.
e9.
Lehrl S, Merz J, Burkhard G, Fischer B: Mehrfachwahl-Wortschatz-Intelligenztest (MWT A/B). [Multiple choice vocabulary intelligence test]. Erlangen: perimed Fachbuch-Verlagsgesellschaft mbH 1991.
e10.
Iverson GL, Zasler ND Lange RT: Post-concussive disorder. In: Zasler ND, Katz DI, Zafonte RD (eds.): Brain injury medicine: principles and practice. New York: Demos Medical Publishing 2007: 373–403.
e11.
Saatman KE, Duhaime AC, Bullock R, Maas AI, Valadka A, Manley GT, Workshop Scientific Team and Advisory Panel Members: Classification of traumatic brain injury for targeted therapies. J Neurotrauma 2008; 25: 719–38. MEDLINE
e12.
Meares S, Shores EA, Taylor AJ, et al.: Mild traumatic brain injury does not predict acute postconcussion syndrome. J Neurol Neurosurg Psychiatry 2008; 79: 300–6. MEDLINE
e13.
Hughes DG, Jackson A, Mason DL, Berry E, Hollis S, Yates DW: Abnormalities on magnetic resonance imaging seen acutely following mild traumatic brain injury: correlation with neuropsychological tests and delayed recovery. Neuroradiology 2004; 46: 550–8. MEDLINE
e14.
Lee H, Wintermark M, Gean AD, Ghajar J, Manley GT, Mukherjee P: Focal lesions in acute mild traumatic brain injury and neurocognitive outcome: CT versus 3T MRI. J Neurotrauma 2008; 25: 1049–56. MEDLINE
e15.
Wallesch CW, Curio N, Galazky I, Jost S, Synowitz H: The neuropsychology of blunt head injury in the early postacute stage: effects of focal lesions and diffuse axonal injury. J Neurotrauma 2001; 18: 11–20. MEDLINE
e16.
Kamikubo T, Ohashi M, Hashimoto K, Miyano S: Cognitive dysfunction in 32 diffuse axonal injury cases. No To Shinkei 2003; 55: 669–73. MEDLINE
e17.
Kothari S, Flanagan SR, Kwasnica C, Brown AW, Elovic EP: Congenital and acquired brain injury. 5. Emerging concepts in prognostication, evaluation, and treatment. Arch Phys Med Rehabil 2008; 89(Suppl 1): S27–31. MEDLINE
e18.
Jennett B: Epilepsy after non-missile head injuries, 2nd ed. Chicago: William Heinemann 1975.
e19.
Annegers JF, Grabow JD, Groover RV, Laws ER Jr, Elveback LR, Kurland LT: Seizures after head trauma: a population study. Neurology 1980; 30: 683–9. MEDLINE
e20.
Yablon SA, Dostrow VG: Posttraumatic seizures and epilepsy. In: Zasler ND, Katz DI, Zafonte RD (eds.): Brain injury medicine: principles and practice. New York: Demos Medical Publishing; 2007: 835–61.
e21.
Angeleri F, Majkowski J, Cacchiò G, et al.: Posttraumatic epilepsy risk factors: one-year prospective study after head injury. Epilepsia 1999; 40: 1222–30. MEDLINE
e22.
Asikainen I, Kaste M, Sarna S: Early and late posttraumatic seizures in traumatic brain injury rehabilitation patients: brain injury factors causing late seizures and influence of seizures on long-term outcome. Epilepsia 1999; 40: 584–9. MEDLINE
e23.
Brodie MJ, French JA: Management of epilepsy in adolescents and adults. Lancet 2000; 356; 323–9. MEDLINE
e24.
Greenberg SM, Vernooij MW, Cordonnier C, et al.: Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 2009; 8: 165–74. MEDLINE
Max-Planck-Institut für Kognitions- und Neurowissenschaften, Leipzig: PD Dr. med. habil. Scheid, Prof. Dr. med. habil. von Cramon
Tagesklinik für Kognitive Neurologie, Universitätsklinikum Leipzig: PD Dr. med. habil. Scheid, Prof. Dr. med. habil. von Cramon
Max-Planck-Institut für Neurologische Forschung, Köln: Prof. Dr. med. habil. von Cramon
1. Gesundheitsbericht für Deutschland 2006.
2. Rickels E, von Wild K, Wenzlaff P, Bock WJ: Schädel-Hirn-Verletzung. Epidemiologie und Versorgung – Ergebnisse einer prospektiven Studie. München: W. Zuckschwerdt Verlag 2006.
3. Kiraly M, Kiraly SJ: Traumatic brain injury and delayed sequelae: a review—traumatic brain injury and mild traumatic brain injury (concussion) are precursors to later-onset brain disorders, including early-onset dementia. Sci World J 2007; 12: 1768–76. MEDLINE
4. Scheid R, Preul C, Gruber O, Wiggins C, von Cramon DY: Diffuse axonal injury associated with chronic traumatic brain injury: Evidence from T2*-weighted gradient-echo imaging at 3 T. AJNR Am J Neuroradiol 2003; 24: 1049–56. MEDLINE
5. Scheid R, Walther K, Guthke T, Preul C, von Cramon DY: Cognitive sequelae of diffuse axonal injury. Arch Neurol 2006; 63: 418–24. MEDLINE
6. Scheid R, Zimmer C, Schroeter ML, Ballaschke O, von Cramon DY: The clinical spectrum of blunt cerebrovascular injury. Neurologist 2006; 12: 255–62. MEDLINE
7. Scheid R, Ott DV, Roth H, Schroeter ML, von Cramon DY: Comparative MR-imaging at 1.5 T and 3 T for the evaluation of traumatic microbleeds. J Neurotrauma 2007; 24: 1811–6. MEDLINE
8. Schroeter ML, Ettrich B, Schwier BS, Scheid R, Guthke T, von Cramon DY: Diffuse axonal injury due to traumatic brain injury alters inhibition of imitative response tendencies. Neuropsychologia 2007; 45: 3149–56. MEDLINE
9. Graham DI, Gennarelli TA, McIntosh TA: Trauma. In: Graham DI, Lantos PI (eds.): Greenfield’s neuropathology. 7th ed. London, New York: Arnold 2002: 823–98.
10. Bigler ED: Neuroimaging correlates of functional outcome. In: Zasler ND, Katz DI, Zafonte RD (eds.): Brain injury medicine: principles and practice. New York: Demos Medical Publishing; 2007: 201–24.
11. Brown AW, Elovic EP, Kothari S, Flanagan SR, Kwasnica C: Congenital and acquired brain injury. 1. Epidemiology, pathophysiology, prognostication, innovative treatments, and prevention. Arch Phys Med Rehabil 2008; 89(Suppl 1): p.3–p.8. MEDLINE
12. Ropper AH, Gorson KC: Concussion. N Engl J Med 2007; 356: 166–72. MEDLINE
13. Deb S, Lyons I, Koutzoukis C: Neurosychiatric sequelae one year after minor head injury. J Neurol Neurosurg Psychiatry 1998; 65: 899–902. MEDLINE
14. Metting Z, Rödiger LA, De Keyser J, van der Naalt J: Structural and functional neuroimaging in mild-to-moderate head injury. Lancet Neurol 2007; 6: 699–710. MEDLINE
15. Niogi SN, Mukherjee P, Ghajar J, et al.: Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury. AJNR Am J Neuroradiol 2008; 29: 967–73. MEDLINE
16. Wallesch CW, Curio N, Kutz S, Jost S, Bartels C, Synowitz H: Outcome after mild-to-moderate blunt head injury: effects of focal lesions and diffuse axonal injury. Brain Injury 2001; 15: 401–12. MEDLINE
17. Wilson JT, Hadley DM, Wiedmann KD, Teasdale GM: Neuropsychological consequences of two patterns of brain damage shown by MRI in survivors of severe head injury. J Neurol Neurosurg Psychiatry 1995; 59: 328–31. MEDLINE
18. Felmingham KL, Baguley IJ, Green AM: Effects of diffuse axonal injury on speed of information processing following severe traumatic brain injury. Neuropsychol 2004; 18: 564–71. MEDLINE
19. Fork M, Bartels C, Ebert AD, Grubich C, Synowitz H, Wallesch CW: Neuropsychological sequelae of diffuse traumatic brain injury. Brain Injury 2005; 19: 101–8. MEDLINE
20. McAllister TW: Neuropsychiatric aspects of TBI. In: Zasler ND, Katz DI, Zafonte RD (eds.): Brain injury medicine: principles and practice. New York: Demos Medical Publishing; 2007: 835–61.
21. Koponen S, Taiminen T, Kurki T, et al.: MRI findings and Axis I and II psychiatric disorders after traumatic brain injury: a 30-year retrospective follow-up study. Psychiatry Res 2006; 146: 263–70. MEDLINE
22. Christensen J, Pedersen MG, Pedersen CB, Sidenius P, Olsen J, Vestergaard M: Long-term risk of epilepsy after traumatic brain injury in children and young adults: a population-based cohort study. Lancet 2009; 373: 1105–10. MEDLINE
23. Temkin NR: Risk factors for post-traumatic seizures. Epilepsia 2003; 44(Suppl 10): 18–20. MEDLINE
24. Duncan JS, Sander JW, Sisodiya SM, Walker MC: Adult epilepsy. Lancet 2006; 367: 1087–100. MEDLINE
25. Werhan KJ: Epilepsy in the Elderly [Altersepilepsie]. Dtsch Arztebl Int 2009; 106(9): 135–42. VOLLTEXT
e1. Teasdale G, Jennett B: Assessment of coma and impaired consciousness. A practical scale. Lancet 1974; 2: 81–4. MEDLINE
e2. Katz DI, Alexander MP: Traumatic brain injury. Predicting course of recovery and outcome for patients admitted to rehabilitation. Arch Neurol 1994; 51: 661–70. MEDLINE
e3. Wilson JT, Pettigrew LE, Teasdale GM: Structured interviews for the Glasgow Outcome Scale and the Extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma 1998; 15: 573–85. MEDLINE
e4. Zimmermann P, Fimm B: Testbatterie zur Aufmerksamkeitsprüfung (TAP). [Test battery for the assessment of attention]. Psychologische Testsysteme. Würselen; 1993.
e5. Wilson B, Alderman N, Burgess PW, Emslie H, Evans JJ: Behavioural assessment of the dysexecutive syndrome. Thames Valley Test Company. Bury St. Edmunds; 1996.
e6. Wolfram H, Neumann J, Wieczorek V: Psychologische Leistungstests in der Neurologie und Psychiatrie. [Psychological performance test in neurology and psychiatry]. VEB Georg Thieme. Leipzig; 1986.
e7. Delis DC, Kramer JH, Kaplan E, Obler BA: The California verbal learning test: Adult version. The Psychological Corporation. San Antonio; 1987.
e8. Härting C, Markowitsch HJ, Neufeld U, Calabrese P, Deisinger K, Kessler J: Wechsler Gedächtnis Test – Revidierte Fassung (WMS-R). [German version of the revised version of the Wechsler memory scale]. Bern: Verlag Hans Huber 2000.
e9. Lehrl S, Merz J, Burkhard G, Fischer B: Mehrfachwahl-Wortschatz-Intelligenztest (MWT A/B). [Multiple choice vocabulary intelligence test]. Erlangen: perimed Fachbuch-Verlagsgesellschaft mbH 1991.
e10. Iverson GL, Zasler ND Lange RT: Post-concussive disorder. In: Zasler ND, Katz DI, Zafonte RD (eds.): Brain injury medicine: principles and practice. New York: Demos Medical Publishing 2007: 373–403.
e11. Saatman KE, Duhaime AC, Bullock R, Maas AI, Valadka A, Manley GT, Workshop Scientific Team and Advisory Panel Members: Classification of traumatic brain injury for targeted therapies. J Neurotrauma 2008; 25: 719–38. MEDLINE
e12. Meares S, Shores EA, Taylor AJ, et al.: Mild traumatic brain injury does not predict acute postconcussion syndrome. J Neurol Neurosurg Psychiatry 2008; 79: 300–6. MEDLINE
e13. Hughes DG, Jackson A, Mason DL, Berry E, Hollis S, Yates DW: Abnormalities on magnetic resonance imaging seen acutely following mild traumatic brain injury: correlation with neuropsychological tests and delayed recovery. Neuroradiology 2004; 46: 550–8. MEDLINE
e14. Lee H, Wintermark M, Gean AD, Ghajar J, Manley GT, Mukherjee P: Focal lesions in acute mild traumatic brain injury and neurocognitive outcome: CT versus 3T MRI. J Neurotrauma 2008; 25: 1049–56. MEDLINE
e15. Wallesch CW, Curio N, Galazky I, Jost S, Synowitz H: The neuropsychology of blunt head injury in the early postacute stage: effects of focal lesions and diffuse axonal injury. J Neurotrauma 2001; 18: 11–20. MEDLINE
e16. Kamikubo T, Ohashi M, Hashimoto K, Miyano S: Cognitive dysfunction in 32 diffuse axonal injury cases. No To Shinkei 2003; 55: 669–73. MEDLINE
e17. Kothari S, Flanagan SR, Kwasnica C, Brown AW, Elovic EP: Congenital and acquired brain injury. 5. Emerging concepts in prognostication, evaluation, and treatment. Arch Phys Med Rehabil 2008; 89(Suppl 1): S27–31. MEDLINE
e18. Jennett B: Epilepsy after non-missile head injuries, 2nd ed. Chicago: William Heinemann 1975.
e19. Annegers JF, Grabow JD, Groover RV, Laws ER Jr, Elveback LR, Kurland LT: Seizures after head trauma: a population study. Neurology 1980; 30: 683–9. MEDLINE
e20. Yablon SA, Dostrow VG: Posttraumatic seizures and epilepsy. In: Zasler ND, Katz DI, Zafonte RD (eds.): Brain injury medicine: principles and practice. New York: Demos Medical Publishing; 2007: 835–61.
e21. Angeleri F, Majkowski J, Cacchiò G, et al.: Posttraumatic epilepsy risk factors: one-year prospective study after head injury. Epilepsia 1999; 40: 1222–30. MEDLINE
e22. Asikainen I, Kaste M, Sarna S: Early and late posttraumatic seizures in traumatic brain injury rehabilitation patients: brain injury factors causing late seizures and influence of seizures on long-term outcome. Epilepsia 1999; 40: 584–9. MEDLINE
e23. Brodie MJ, French JA: Management of epilepsy in adolescents and adults. Lancet 2000; 356; 323–9. MEDLINE
e24. Greenberg SM, Vernooij MW, Cordonnier C, et al.: Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 2009; 8: 165–74. MEDLINE