SPECT BRAIN PERFUSION FINDINGS IN MILD OR MODERATE TRAUMATIC BRAIN INJURY

SPECT brain perfusion studies have been playing an important role in understanding the patho-physiology, medical and socio-economic decision-making involving mild head injury patients (^(33-38).^. It is highly sensitive for detecting regional cerebral blood flow (rCBF) disturbances in-patients with acute head injury⁽³⁰⁾. Many studies on patients with head injury have already demonstrated that brain perfusion SPECT can depict larger rather than smaller and more numerous lesions than on CT. Most of these studies however have addressed rather severe trauma cases^(14,15). In mild traumatic brain injury there is increasing evidence in the literature showing the superiority of SPECT over CT in detecting abnormal brain perfusion findings ^(1,16-26). The sensitivity of CT in mild to moderate trauma is less than 25%⁽¹⁵⁾. While SPECT imaging does not replace traditional structural imaging modalities for identifying major lesions, hematomas, or edema, brain SPECT does play an important role in assessing cortical, basal ganglia, and thalamic perfusion alterations resulting from trauma.

Our findings suggest that basal ganglia and thalamic perfusion abnormalities are more common than previously reported. Previous reports described frontal and temporal lobes to be the most common abnormalities^(14-26). In our subset of patients who suffered traumatic brain injury without loss of consciousness, basal ganglia hypoperfusion abnormalities are second to frontal lobes abnormalities and more common than temporal lobe abnormalities. Our results further confirmed that the SPECT brain perfusion studies are more sensitive than X-ray CT in detecting brain lesions following mild / moderate traumatic brain injury. We previously reported that early imaging less than three months following the incident detects more lesions than in delayed imaging performed more than three months after the accident ⁽³⁹⁾. The present findings offer new and objective evidence that "mild" head injury may be accompanied by objective neurotrauma not revealed by other imaging procedures which are less sensitive to "minor" head injury, especially in the absence of areas of hematoma, contusion, mass effects and edema.

It is noteworthy that BG and thalamic lesions are located in areas protected from lesser impact injury. It is important to be aware of the range of physiological and traumatic circumstances that are hypothesized to contribute to patient's symptoms and to the SPECT-detected lesions in the mild traumatic brain injury. These include: 1. Primary physical traumatic effects upon (a) the parenchyma of the brain; (b) the arteries in the neck and head; 2. Disturbance of brain autoregulation; 3. Intracellular damage (damage to the blood-brain barrier; neurotoxic cascades) 4. Transneuronal degeneration and atrophy consequent to parenchymal trauma (direct injury and vascular dysfunctions); and 5. Diaschisis consequent to atrophy and dysfunction of nuclei subserving distant incoming circuits.

Because of many unclear issues in our practice and in dealing with patients with traumatic brain injury, we aim in this presentation to review some of the facts that have been reported in the literature related to mechanism and pathology of traumatic brain injury.

The brain, floating in the CSF inside the skull, is known to be a penetrable, deformable, soft, and not very elastic structure. The skull and the scalp, in addition to the dura and dural extensions, serve as a cushion to the brain against impacting forces. When the forces of traumatic impact on the skull exceeds local elasticity, it induces permanent deformation. Further trauma is caused by the brain being pushed against fixed structures such as the internal surface of the skull, meninges, and blood vessels. When one portion of an anatomic structure is fixed in place and the other is moved by impact, creating acceleration or deceleration, a shearing force occurs, a significant cause of trauma. The shearing effects take place within the layers of the brain , between the brain and its entering and exiting vascular supply, especially to the hypothalamus, infandibulum, pituitary gland seated in the sella turcica, and occasionally the cranial nerves. Movement of the brain is expected to damage the pituitary stalk, the perforating vessels to the hypothalamus from the anterior cerebral arteries and pituitary portal veins^(40-44). Minor head injury has been identified experimentally as causing meningeal thickening, discoloration of the cerebral cortex from old extravasated blood, contusions and lacerations⁽³⁴⁾. Under impact conditions, the vascular tissues of the brain undergo sudden deformations beyond their recoverable limit. The vascular tissue is a very complex structure with different responses to rapid mechanically induced trauma. The three-dimensional vascular distribution of vessels in the brain contributes to the overall stability of the brain ⁽⁴⁵⁾.

Major blood supply to the basal ganglia and thalamus originate from vascular branches from the anterior and middle cerebral arteries, and the posterior cerebral artery which arise from the circle of Willis. ^(46-47 ) The multiple branches of these complex structures render the blood supply vulnerable to physical trauma and disruption of autoregulation and mass effects.

Sympathetic fibers reach cerebral vessels by three routes: 1) the carotid artery territory via post ganglionic fibers that originate in the superior cervical ganglia; innervation of the vertebrobasilar territory via fibers that arise from the stellate ganglion; from the stellate ganglion following the tunica adventitia of the common and internal carotid arteries possibly innervating the rostral part of the Circle of Willis⁽⁴⁸⁾. As the carotid artery emerges from the cavernous sinus, it is surrounded by a sympathetic plexus ⁽⁴⁷⁾. The vasomotor center (anterior lateral portion of the medulla) has noradrenergic fibers that excite the vasoconstrictor neurons of the sympathetic nervous system (SNS), effecting the vasculature of the brain. Cerebral blood vessels are also innervated by intraparenchymal fibers, which originate from the locus ceruleus. Intracerebral arterioles are supplied with perivascular sympathetic nerves, whereas cerebral microvessels, capillaries and venules may be supplied with or closely associated with intraparenchymal adrenergic nerves.

Ordinarily cerebral autoregulation prevents major changes stemming from sympathetic stimulation. However, cerebral sympathetic stimulation can markedly constrict the cerebral arteries in order to prevent high pressure from reaching the smaller blood vessels and causing stroke ^(48-50). Early and late vasospasm, involving the large basal intracranial arteries (middle cerebral and basilar), is considered to be a significant entity in head trauma, occurring in up to 25% of patients with head injury ⁽⁴⁰⁾. Cerebral arterial spasm can occur in-patients whose CT scans did not show subarachnoid or intracerebral blood. It has been deemed unlikely that posttraumatic cerebral arterial spasm is caused by elevated intracerebral pressure. Onset of vasospasm can occur from 48 hours to 7 days later ^(49-50). Ischemia (associated with vasospasm or mass effects) impairs the metabolic need of the brain, setting into motion multiple mechanisms of toxic metabolite formation and cell destruction. Blunt trauma was found to be able to cause cerebral hypoperfusion. This association is statistically stronger for the most severely injured patients ⁽⁵⁰⁾. The intracranial artery can be injured by direct damage to neck structures, i.e. impact, stretching, tearing or compression of the intracranial arteries and other cervical vessels^(51,52) caused by impact or hyper-extension / hyper-reflexion and rotation in various planes ("whiplash"). Cerebro-arterial spasm can occur secondary to sudden traction on the carotid artery sheath at the base of the brain, with symptoms of vascular type of headaches, and feeling of being dazed or stunned⁽⁵²⁾. Shearing effects may injure the intracranial arteries as it emerges from the cavernous sinus, and can create diffuse brain injury since the brain moves past the arterial tree⁽⁵³⁾. The combination of carotid occlusion and brain impact is more severe than carotid occlusion alone. Traumatized cerebral vasculature seems unable to respond to reduced perfusion pressure associated with carotid artery occlusion ⁽⁵⁴⁾.

Cerebral vasoreactivity is under the control of the SNS through complex CNS circuits (medulla oblongata; pons; hypothalamus), feedback through the extra-cellular fluid (electrolytes; hormones), temperature and negative feedback baroreceptor mechanism of the tractus solitarius^(55). Cerebral vasospasm can be relieved through electrical stellate or cervical ganglia blocks⁽⁵⁶⁾. In a personal communication (Fritz Jenkner, M.D., Vienna, Austria), hemispheric flow measured by electrical resistance ("rheoencephalography") increased towards normal levels after stellate block in 11 patients who had symptoms secondary to decreased cerebral flow due to various reasons including head trauma.

Neuronal integrity is maintained through control of brain metabolism and blood gas level, affected by a variety of metabolic and neurogenic effect⁽⁵⁶⁾. SPECT signs of hypoperfusion have been attributed to loss of cerebral autoregulation after head trauma including minor head injury⁽⁵⁷⁾. Vasospasm is described as occurring after 48 hours. Brainstem damage or subarachnoid hemorrhage is associated with vasospasm independently of dysregulation. Impaired cerebral autoregulation of vasomotor control occurs after minor head injury⁽⁵⁸⁾ and is associated with poor outcome. After impact injury (rat model) there is transient hypertension and increased blood flow, followed by blood flow reduction below control values within minutes^(56-59). Ischemia and luxury perfusion occurs at different post-trauma periods⁽⁶⁰⁾. Vasospastic ischemia is most common after injury but can occur throughout the acute recovery period. After head injury and hypoperfusion, cerebral metabolic rate of oxygen tends to be highest very early and decreasing over the first 1-5 days⁽⁶¹⁾. While blood flow measurements vary with location, the PCS is associated with slowed cerebral circulation for up to 3 years^(62).. Arterial hypotension or increased intracranial pressure can result in lowered cerebral perfusion pressure. Sudden increases in blood pressure can be transmitted to the brain’s microcirculation, contributing to secondary hemorrhage and edema. Loss of autoregulation may occur in some areas but not others⁽⁶³⁾.

Reperfusion following resolution of ischemia or vasospasm leads to additional neurological injury: Phagocytic damage to the endothelium and surrounding tissues; release of oxygen-derived free radicals ⁽⁶⁴⁾. This creates damage to vascular, neuronal, and glial membranes, with excitotoxic, intracellular calcium overload and excitatory amino acid release, i.e., glutamate ^(65-67).

Lesions may account for some subtle neurobehavioral dysfunctions in the inter-connected thalamus and basal ganglia^(68,69). The basal ganglia is associated with multiple behavioral disorders that might occur following mild or moderate traumatic brain injury. BG circuits and connections (including the cortex) have been implicated in disparate functions dependent upon circuits and nuclei involved: These included repeated skilled movement and idiomotor apraxia⁽⁷⁰⁾. Depression among patients with left BG lesions may be due to disrupted ascending noradrenergic / serotonergic pathways⁽⁷¹⁾; species specific sexual behavior⁽⁷²⁾; movement disorders and behavior problems (abulia or disinhibition)⁽⁷³⁾; dementia associated with involuntary movement disorders⁽⁷⁴⁾; in Parkinson’s disease and Huntington’s disease, intellectual and emotional disorders⁽⁷⁵⁾. The potential for BG lesions to be caused by transneuronal degeneration is raised by the finding that thalamic (subcortical) atrophy is related to injury severity, degree of brain atrophy and the presence of nonthalamic cortical or subcortical lesions, i.e. diaschesis ^(75,76).

The thalamus participates in numerous neurobehavioral functions through its location in the limbic circuit, and as a relay for diffuse stimuli influencing arousal and topographic sensory stimuli, and output for motivational systems^(76,77). The intra-thalamic laminar nuclei (ILN) may be the thalamic pacemaker, and are involved in functions disturbed in TBI (wakefulness, desynchronized sleep and pain). They receive topographically organized projections from the cerebral cortex, reticular formation, basal ganglia, cerebellum and the brainstem up to the midbrain and superior colliculus. The ILN projects to the cerebral cortex (primarily frontal, medial and dorsolateral cortex), the striatum and substantia nigra, limbic forebrain, amygdala and hippocampus.

We realize that this report lacks a direct comparison with a normal control group (a problem many institutions face), and that there is a high false positive rate and non-specificity of SPECT brain perfusion abnormalities in head trauma and other disorders. Nevertheless this group was a part of a much larger series, in which all studies were read blindly to the patients’ history and presenting symptoms as described above.

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