MEDICINA (2002) Vol. 38, No. 3 - http://medicina.kmu.

lt 243

Brain contusion: morphology, pathogenesis, and treatment

Vytautas Ragaišis
Clinic of Neurosurgery, Kaunas Medical University Hospital, Lithuania

Key words: brain contusion, pathogenesis, secondary neuronal damage, intensive care,
surgery.
Summary. Focal cerebral contusions can be dynamic and expansive, leading to a de-
layed neurological deterioration. In head – injured patients, the rise in intracranial pres-
sure (ICP), subsequent to uncontrollable swelling, is the only and the most frequent cause
of death. Studies show that brain swelling, after traumatic brain injury (TBI), is caused by
brain edema rather than cerebral blood volume (CBV). CBV is reduced in proportion to
cerebral blood flow (CBF) reduction, following a severe TBI. Cerebrovascular damages,
leading to subsequent reductions in regional CBF, may play an important role in secondary
cell damages following TBI. The histological examination revealed the formation of
microthrombosis in the contused area, extending from the center to the peripheral areas
within 6 hours after injury. In the pericontusional zone and surrounding parenchyma,
vasoresponsivity may be nearly three times normal, which suggests hypersensitivity to hy-
perventilation and other phenomena.
Glutamate is the most widely distributed excitatory neurotransmitter in the mammalian
brain. However, when glutamate is present in excessive quantities, it may overactivate spe-
cific ion channels, especially the N-methyl-D-aspartate channel. A shift of potassium into
the extracellular space will result in rapid swelling of astrocytes, which absorb quantities
of potassium to preserve ionic homeostasis. This process may cause rapid cytotoxic edema,
which is probably, a major factor in causation of posttraumatic raised ICP. The presence of
a focal contusion and primary or secondary ischemic events were the clinical features most
strongly correlated with high dialysate of glutamate. Raised ICP was significantly more
common, and outcome was worse in patients with high levels of glutamate.
Contusion is a key factor in the development of blood brain barrier (BBB) permeability.
BBB endures at least 7 days post TBI. Biphasing opening of the BBB, following head trauma
and a possible second wave of secondary brain damage, was confirmed. Brain tissue pO2
monitoring might become an important tool in the treatment regime for TBI patients.
Histologically the loss of CA3 pyramidal cells in the hippocampus was observed ipsilat-
erally in the cortical contusion and bilaterally in diffuse axonal injury. Aggressive, early
hyperventilation after TBI augments neuronal death in CA3 hippocampus.
Due to high mortality associated with such cerebral contusions, a standard practice has
evolved into evacuating contusions in patients who had deterioration in the level of con-
sciousness, lesions more than 30 sec and CT suggestion of raised ICP.

Severe head trauma is one of the prevailing causes
of death in the developed countries. According to sta-
tistics, 100,000 people die from trauma in the United
States every year. Severe head injuries constitute ½
of these deaths. Hundreds of thousands of head trauma
survivors suffer from long-term disabilities (1). After
severe and moderate head injuries, parenchymal dam-
age is detected in over 55% of cases (2). For over
50% of patients, contusion foci are located in surgi-
cally favorable frontal and temporal lobes. Until quite
recently, little emphasis has been placed on the analy-
sis of reasons of the neurological state deterioration
after hospitalization. In 1993, Stein et al. proved that
the deterioration of the neurological state of hospital-
ized patients is an indication of poor outcome (1). By
implication, the main task of a surgeon is to avoid or

Correspondence to V.Ragaišis, Clinic of Neurosurgery, Kaunas Medical University Hospital, Eivenių 2, 3007 Kaunas,
Lithuania. E-mail: vragaisis@yahoo.com
244 Vytautas Ragaišis
reduce secondary neuronal damage, which, in effect,
causes the deterioration of the neurological state (1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16). It is thus
necessary to reduce ICP or to maintain cerebral
perfusion pressure (CPP) at 60-70 mm Hg. Neuro-
logical state is classified as deteriorated when Glaskow
Outcome Scale (GCS) is reduced by 2 scores and the
pupils are asymmetric (>1 mm) as well as areactive.
These symptoms indicate the need to introduce
correctives in treatment. Without any changes in treat-
ment, mortality rates increase from 9.6 % to 56.4%,
whereas good results, according to GCS, decrease
from 68 to 29 % (1). It has been proved that subse-
quent neurological state deterioration is caused mainly
by brain parenchyma damage.
BC or BC with hematoma comprises approximately
60 % of the totality of intracranial injuries (3, 4, 5, 6, 7,
8, 16, 17, 18). Contusions leading to the neurological
state deterioration are more common in the age group
of over 40 (56 %). Sometimes initial brain damage
seems mild or moderate immediately after the injury
(2). In patients with BC, neurological deterioration, on
average, manifests 6 hours after the trauma (77.5 %),
while neurological worsening caused by extracerebral
hematomas occur up to 6 hours after the injury (19).
For children and young people, GCS score <9 on ad-
mission was predictive of either severe neurological
state deterioration or death caused by multiple contu-
sion, brain swelling, and brain herniation, i.e. a com-
plex of symptoms indicative of a dynamic, progres-
sive nature of head injury (11). In 1998, Firsching et
al. performed magnetic resonance image (MRI) scan-
ning of over 100 severely head-injured patients of poor
neurological state immediately after the trauma and
detected primary brain stem contusion (pons), which
was not visible on CT. In the majority of cases, these
patients exhibited poor outcome (20).
Studies on the subject emphasize the importance
of an in-depth knowledge of pathogenesis for adequate
clinical management of BC. Recent findings throw new
light on pathogenesis and secondary neuronal dam-
age. BC used to be defined as traumatic necrosis fol-
lowed by reabsorption. Such a view defies the pro-
gressive nature of the injury, though its dynamics is
implied in the commonly acknowledged fact of reab-
sorption. The currently used definition of BC points
out that it is a dynamic and expansive process inevita-
bly leading to the deterioration of the neurological state
(21). Dynamic processes are most pronounced in neu-
rons, glial tissue, and blood vessels. In the early stages,
microscopic examination reveals perivascular hemor-
rhage, astrocytic swelling, changes in the myelin, infil-
tration of the macrophages, apoptosis, phagocytosis,
and atrophy (12). The majority of neuro-researchers
distinguish the following zones in the severely injured
brain: contusional, pericontusional (synonyms -
perilesional, hypoperfusional, ischemic, edemic). Very
important is hypoperfusive zone, which is very dynamic
and apt to expansion in cases of inadequate treatment
(8, 12, 17, 22, 23).
Several pathophysiological processes triggered by
BC are of special significance, and disturbances in
cerebral blood flow are among them. Severe head in-
jury causes disturbances both in hemispheric and re-
gional cerebral blood flow (CBF). Examinations show
that CBF in the contusion foci is 4.7 ml/100g/min., and
it is 16-18 ml/100g/min. in the hypoperfusional zone.
In the normal brain, CBF is >50 ml/100g/min. (24).
Ischemic threshold is commonly considered to be 18-
20 ml//100g/min. Disturbances in blood vessel sensi-
tivity are frequent in hypoperfusional zone and are
related to the increase and, even more so, to the de-
crease of arterial blood pressure (ABP), the increase
of ICP, the decrease of CPP, and changes in ventila-
tion (12, 18, 24, 25). In hypoperfusional zone, blood
flow decreases 3 hours after the injury, while the prob-
ability of blood vessel thrombosis significantly increases
after six hours postinjury (26). Adequate treatment
and permanent multimodal monitoring enable to pre-
vent expansion of the hypoperfusive zone into the nor-
mal brain for approximately 10 days postinjury and
even longer periods. An important fact to be pointed
out is the absence of reperfusion in this zone (18).
Lebedev reports cases of hypoperfusional zone re-
duction (27). Erratic clinical management brings about
the increase of this zone and its expansion into the
normal brain, which causes an irretrievable brain dam-
age. Hypoperfusional zone can encompass approxi-
mately 15% of brain hemisphere. The aggressive ex-
pansion of the volume of the contusion focus increases
the secondary neuronal damage. In patients with poor
outcome, hypoperfusional zone can be very extensive
and encompass a large bulk of brain hemisphere (3, 4,
5, 24, 28, 29). Cerebral autoregulation is an ability to
maintain normal CBF despite changes in CPP; BC is
likely to cause severe damage in cerebral autoregula-
tion. Cerebral autoregulation is based on active varia-
tions of cerebrovascular resistance. ABP, ICP, and
CBF measurements provide important data about ce-
rebral autoregulation (30, 54). We perform ICP and
ABP slow wave simultaneous measurements to in-
vestigate their correlation.
Very important for brain contusion pathogenesis is
the increase of glutamate, its coagonist aspartate, and
MEDICINA (2002) Vol. 38, No. 3 - http://medicina.kmu.lt
 Brain contusion: morphology, pathogenesis, and treatment
structural amino acids (threonine and valine) in paren-
chyma microdialysis probes or in cerebrospinal fluid
(CSF). Glutamate is an excitatory neurotransmitter in
brain. Evidence has been provided on its significant
role in “the causation of both acute and chronic neu-
ronal damage.” Recent studies state that “many of
the normal physiological processes of the cortex and
the hippocampus, in particular, are thought to depend
on this neurotransmitter function of glutamate.” The
increase of glutamate significantly activates ion chan-
nels, N-methyl-D-aspartate channel, in particular. In
a random manner, sodium and calcium penetrate into
cells while potassium enters the extracellular space.
“When this process is rapid, it can result in massive
accumulation of intracellular calcium with rapid neu-
ronal death - ‘fast excitotoxicity.’” Such dynamics
leads to a fast neuronal death that can occur during
the first day after the trauma. In case of delayed en-
try of calcium, neuronal death can be traced within
the period of 5-7 days after the injury (7). The pen-
etration of potassium into the extracellular space causes
a rapid swelling of astrocytes. This can, in turn, lead
to “cytotoxic edema,” which is thought to cause the
increase of intracranial pressure. The investigation of
morphological changes has provided more insight into
the mechanism of astrocyte swelling (7, 12, 16). The
implementation of the microdialysis technique revealed
a rise of glutamate in the extracellular space after se-
vere head injury and stroke. The blockage of glutamate
by N-methyl-D-aspartate channel antagonists de-
creases the secondary damage of neuronal cells. It
has been detected that the biggest amounts of this
neurotransmitter are found in cases of brain contusion
(>20 mmol/L), subdural hematoma and diffuse injury
(< 20 mmol/L), and epidural hematoma (about 3 mmol/
L). These findings suggest that the more severe brain
damage, the higher the increase of glutamate (7). Post-
traumatic increase of glutamate in the cerebrospinal
fluid is indicative of neuronal and glial damage as well
as cytotoxic rather than vasogenic edema (31).
In a lot of cases, BC is accompanied by the fol-
lowing parallel states, which can cause brain ischemia:
hypoxemia (PaO2 <60 mm Hg), hypotension at mean
arterial blood pressure (MABP) <50 Hg (for >30 min.
prior to resuscitation), hemispheric CBF <20 ml/100g/
min., herniation (fixed dilated pupil), and CPP <50 mm
Hg for >30 min. (7).
It has been detected that ischemia is an important
factor influencing the increase of glutamate, which is
>80 mmol/L, in cases of brain contusion, and 5-20
mmol/L in the absence of brain contusion. This im-
plies that brain contusion is crucial for the behavior of
MEDICINA (2002) Vol. 38, No. 3 - http://medicina.kmu.lt
245
glutamates and for the increase of structural amino
acids (threonine and valine) resulting from neuronal
death (7, 16). Following this study, it can be suggested
that the combination of ischemic events and brain con-
tusion causes a more severe secondary neuronal dam-
age.
The data lead to an assumption that the rise of
glutamate in brain microdialysate is followed by the
increase of ICP, decrease of CPP, progressive dam-
age in hippocampus, brain stem, cerebellum, and,
inevidently, in the pericontusional area. The increase
of glutamate >20 mmol/L is suggestive of poor out-
come. When glutamates increase up to 50-100 mmol/
L, neuronal death can be detected within several hours
due to their overexcitation. Studies on animals and
humans indicate that contusion in one hemisphere leads
to neuronal death not only in the focus of BC but also
in the brain stem, cerebellum, and, especially, in the
ipsilateral hippocampus. In cases of contusion in both
hemispheres, neuronal death occurs in bilateral hip-
pocampus, brain stem, and cerebellum (3, 4, 5, 7, 8,
13, 14, 15, 18, 20, 21, 26, 28, 32, 33, 34, 35). Second-
ary hippocampus damage can evoke posttraumatic
epileptic seizures because hippocampus modulates
epileptogenic activity (36, 37, 38). The rise of the neu-
rotransmitter glutamate causes increased
hyperglycolysis, which, in turn, affects a further in-
crease of this neurotransmitter and, in this way, en-
hances the activity of this destructive circle. If CPP
remains <70 mm Hg for more than 1 hour, the level of
glutamate increases, and brain becomes very vulner-
able. The increase of the glutamate concentration is
not even; the highest levels of glutamate have been
detected within 9 days postinjury. It has to be pointed
out that even in cases of normal CPP (80-110 mm
Hg), the occurrence of an epileptic seizure causes a
significant increase of glutamate (30-60 mmol/L (39).
The above-described processes can be defined as a
chain reaction to be interrupted by a careful clinical
management.
Clinical testing of “Selfotel,” the NMDA receptor
antagonist, did not come to expectations. “Selfotel”
proved to be ineffective at high levels of glutamate
(e.g. increase of 50 times normal). Data on 693 pa-
tients demonstrate that satisfactory results were seen
only in patients with epidural and subdural, i.e.
extracerebral hematomas, in cases of mild brain pa-
renchyma damage (40). The use of “Selfotel” for the
treatment of animals with brain contusion demonstrates
better results (28).
The damage of brain blood barrier (BBB) is also
very important (4, 5, 14, 41, 42). Approximately a
246 Vytautas Ragaišis
decade ago, the majority of neurosurgical research
emphasized the vasogenic origin of posttraumatic brain
swelling. At present, many leading scholars in the field,
such as Marmarou, Bullock, Schroder, and others, high-
light the importance of cytotoxic brain edema (7, 12).
A closely related problem is the decrease of BBB. In
literature on the subject, different data on the BBB
damage time are reported. Baldwin et al., for example,
indicates two stages. During the first stage, BBB de-
creases in brain cortex and hippocampus 1 hour after
the injury. After 3 hours, BBB returns to the initial
level. During the second stage, BBB decreases in brain
cortex and hippocampus 1-2 days postinjury (5).
Soares et al. detected the decrease of BBB in brain
cortex and hippocampus 2-12 hours postinjury followed
by its restoration to the initial state within a three-day-
period (19). Holmin et al. report on the decrease of
BBB 2 days after the injury, reaching its maximum 5-
6 days postinjury. BBB restores to normal within 16
days (41). The decrease of BBB causes not only
vasogenic edema but also inflammatory processes,
which, in turn, can cause secondary neuronal damage
(41, 42).
Katayama et al. reveal one more aspect of the
pathogenesis of the BC focus volume increase. They
detected a rapid increase of osmolarity in the BC fo-
cus due to the neuronal cell disintegration, homogeni-
zation, and metabolic disturbances. Such “mass” is
inclined to reabsorb liquids; a process that can be re-
ferred to the increase of osmolarity in this mass, pro-
vided CBF remains sufficient (26).
The increase of ICP and the decrease of CPP will
be mentioned only in passing because this subject is
not the primary intent of the present study. In order to
maintain optimal CPP and to retain optimal brain oxy-
gen saturation, it is essential to manage ICP. When
ICP is >20 mm Hg, it is considered pathological, and,
when ICP is over 40 mm Hg, it is very dangerous.
ICP is one of the main indicators of poor outcome,
though there is an alternative view foregrounding the
significance of CPP. The decrease of ICP is essential
for the increase of CPP. Regardless of CPP, the initial
ICP of >20 mm Hg yields a poorer outcome than that
of <20 mm Hg. With ICP greater than 20 mm Hg, it is
very difficult to maintain CPP in the range of 70-80
mm Hg. The increase of CPP at the expense of the
increase of MABP does not yield good results. CPP
should not be allowed to decrease below 60-70 mm
Hg (1, 43). Until quite recently, ICP was believed to
be uniform in the entire skull cavity. Lately, however,
not only supra-infratentorial but also interhemispheric
gradients of ICP have been detected in patients with
BC (44). These findings help to explain the deteriora-
tion and differences of CPP and brain parenchyma
oxygen saturation in different brain locations (22, 31,
35).
ICP and CPP monitoring does not reflect brain
oxygen consumption. Recent management schemes
propose the estimation of direct parenchyma satura-
tion for oxygen. This method offers higher accuracy
(>90%) compared with that of the oxygen blood satu-
ration method in jugular bulb (accuracy 46 %) and
excludes risk factors such as vein sinus trombosis (45).
In the brain contusion focus, pO2 is constantly below
hypoxic threshold (decreases by 70%) and is not af-
fected by hyperventilation (HV), a fact that is indica-
tive of the brain death zone. In the pericontusional zone,
pO2 decreases, while the reaction of blood vessels to
HV, ABP, and ICP as well as CPP changes is signifi-
cantly disturbed. In the normal brain, both pO2 and
blood vessel reactivity is not impaired (34). Aggres-
sive HV (PaCO2 21mm Hg) radically reduces
hipoperfusional zone saturation (by ½) even when CPP
is above 60 mm Hg. This is due to the changes in the
reactivity of blood vessels in the pericontusional zone
and severe vasoconstriction (24, 31, 34, 35). BC is
thus a very aggressive process triggering many patho-
logical mechanisms that, in turn, activate new pro-
cesses, many of which still need further investigation
(37).
With regard to the stated above, it would be perti-
nent to recapitulate BC-induced changes in brain and
the body: changes in ABP, the decrease of regional
and hemispheric CBF, the increase of contusion focus
osmolarity, the expansion of water into contusion fo-
cus, the increase of ICP, the decrease of CPP, the
occurrence of brain ischemia, the increase of glutamate
concentration and structural amino acids, the swelling
of the glial tissue, the decrease of BBB, the triggering
of inflammatory responses, the increase of platelet
cells activating materials and free radicals, changes in
brain pH, the possibility of brain hyperemia occurrence,
and the decrease of brain saturation. Neuronal death
is detected in the BC focus and the surrounding tissue
as well as in the hippocampus, brainstem, and cer-
ebellum (4, 5, 7, 12, 14, 16, 18, 24, 25, 26, 30, 32, 41,
42). There exists a controversial view on the role of
brain hyperemia: some authors regard it as a negative
factor while others point out its beneficial effects (33,
41).
These complex changes and the morphology of the
dynamics of the hypoperfusive zone play an important
role in the consideration of an effective surgical treat-
ment. During surgical treatment, a histological exami-
MEDICINA (2002) Vol. 38, No. 3 - http://medicina.kmu.lt
 Brain contusion: morphology, pathogenesis, and treatment 247

nation of the pericontusional zone was performed by
an electronic microscope. The examination revealed
that, in extracellular spaces, swelled astrocytes exter-
nally compress blood microvessels obstructed by red
cells and white cells. The fact that the blood vessel
endothelium is not impaired confirms the astrocytal
origin of blood microvessel compression (7, 46).
Lebedev claims that astrocytes exhibit changes dur-
ing the first minutes after the trauma (27).
Neuronal death caused by brain contusion occurs
at different time intervals in different locations. In brain
cortex, it can occur 24 hours postinjury, while maxi-
mum apoptosis is observed on 7th day after the trauma.
In hippocampus, it occurs within 48 hours and in thala-
mus within 14 days (8). Baldwin reports cases of neu-
ronal death in hippocampus 24 hours postinjury and
states that BC causes the death of 41% of neurons in
this zone (5). A question then poses itself whether
and how this posttraumatic chain reaction can be in-
terrupted and what clinical management can yield best
results.
As it has already been stated, brain contusion is a
dynamic and expansive process having pronounced
effects not only in the vicinity of the contusion focus
but also in more remote areas such as hippocampus
and the brain stem. Inadequate treatment and the ab-
sence of monitoring enhance these effects. The rec-
ommended optimal MABP is 140-70 mm Hg and the
optimal CPP range is between 105-70 mm Hg (22).
Some authors recommend maintaining CPP above 70
mm Hg, and they hold that the decrease of CPP un-
der 30 mm Hg can double the contusion focus (1, 22,
29). Some authors explore the influence of MABP on
the dynamics of the BC volume. For example, the rise
of MABP up to 140 mm Hg increases the contusion
volume by 15%, while the fall of MABP up to 50 mm
Hg doubles the contusion volume (22).
The problem of HV as a means of minimizing ICP
also needs to be considered. For approximately 20
years, HV has been a commonly used technique for
the reduction of ICP. Recent research emphasizes
negative effects of aggressive HV and points out a
high degree of risk involved in its use (47). It has been
indicated that the use of HV in the clinical manage-
ment of BC can cause a 40% increase of neuronal
apoptosis in hippocampus at PaCO2 <25 mm Hg af-
ter 5 hours. This occurs only in cases of BC. The
expansion of contusion focus has also been detected,
and this is referred to vasoconstriction, especially in
the pericontusional zone, reduced CBF, alkalosis, and
increased negative effects of glutamate (9). As it has
already been stated, the increase of the contusion fo-
cus, along with its penetration into the normal brain, is
determined by the expansion of the pericontusional
zone due to highly distorted and raised vasoreactivity
(6, 12, 40). In recent studies, the majority of research-
ers claim that conservative treatment of BC is inef-
fective. BC focus is a zone of dead brain, an urgent
removal of which can hinder its expansion into the
normal brain (46). In many countries, patients with
BC undergo surgical treatment. The main criteria for
surgical treatment are the following: the deterioration
of conscious, according to the GCS; contusional focus
of >30 cc; the symptoms of increased ICP (com-
pressed brain ventricles, compressed or invisible basal
cisterns, and the midline shift on CT (21, 48). The
present survey of literature on BC provides sufficient
evidence to claim that surgical treatment can reduce
the secondary neuronal damage and improve short-
term as well as long-term treatment results.

Galvos smegenų sumušimo (kontūzijos) morfologija, patogenezė

ir gydymo principai

Vytautas Ragaišis
Kauno medicinos universiteto klinikų Neurochirurgijos klinika

Raktažodžiai: galvos smegenų kontūzija, patogenezė, antrinis neuronų pažeidimas, intensyvioji terapija,
chirurginis gydymas.

Santrauka. Galvos smegenų kontūzijų gydymas yra labai aktualus. Dėl chirurginio galvos smegenų kontūzijos
gydymo indikacijų ilgai buvo diskutuojama, tačiau pastaraisiais metais prieita vieningos nuomonės. Įrodyta, jog
kontūziniai židiniai nėra stabilūs, jie didėja, o dėl jų poveikio padidėja intrakranijinis slėgis, atsiranda galvos
smegenų įstrigimo pavojus. Kuo intrakranijinis slėgis didesnis, tuo pacientų prognozė yra blogesnė. Be to,
galvos smegenų kontūzija sukelia antrinių morfologinių neuronų pokyčių atokiose nuo kontūzinio židinio galvos

MEDICINA (2002) Vol. 38, No. 3 - http://medicina.kmu.lt

248 Vytautas Ragaišis
smegenų vietose: hipokampe, galvos smegenų kamiene. Tik žinodamas galvos smegenų kontūzijos patogenezę
ir skyręs reikiamą gydymą, gydytojas galės sumažinti antrinį neuronų pažeidimą, sukeltą galvos smegenų
kontūzijos, ir pasiekti geresnių gydymo rezultatų. Tikimasi, kad šiame straipsnyje pateikiama literatūros apžvalga
dėl rekomenduojamos galvos smegenų kontūzijos gydymo taktikos galėtų tapti pagrindu diskusijai apie tokių
pacientų gydymo koregavimą.
Adresas susirašinėjimui: V.Ragaišis, KMUK Neurochirurgijos klinika, Eivenių 2, 3007 Kaunas
El. paštas: vragaisis@yahoo.com
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