I. Craniofacial injury and the mechanism of injury
Traumatic cranial brain injury is still a major problem affecting health. The United States each year to more than 2 million patients, of which about 7,500 people died, 125,000 people disabled. The United Kingdom each year to more than 1 million, the mortality rate of 9/100,000, accounting for 1% of all deaths in hospital; 15% to 20% of deaths in the age, between 5 and 35 years. Most of the causes of injury are fall injuries, followed by fights and traffic accidents. At present, the severity of brain injury is increasing, traffic accidents have a major role in it: although its cause of cranio-cerebral injury accounted for 13% of hospitalized patients, but the mortality rate is as high as 58%. It is now believed that traumatic brain injury, which is initially only partial, is followed by many secondary damages in the next few hours to days.
Graham et al. found that 90% of patients who died from traumatic brain injury ( tBI) had ischemic changes as the main mechanism of secondary injury. The cause of increased intracranial pressure ( iCP) is mostly cytotoxic edema in the acute phase 24 to 36 hours after injury without hematoma, and in a few cases vasogenic edema due to blood-brain barrier damage, while brain swelling due to vascular congestion plays a much smaller role than previously thought; in the later phase of acute injury, or at the end of day 3 or beginning of day 4, the cause of elevated iCP may again be vascular congestion, the Because cerebral blood flow (cBF) has increased on day 2 or 3, and the integrity of the blood-brain barrier has been restored within 12 to 24 hours after injury. When iCP is elevated, intracranial buffering is fastest in the volume of intracerebral blood, followed by cerebrospinal fluid. When buffering capacity is depleted, iCP increases dramatically. When iCP increases above 20 to 25 mmHg (1 mmHg = 0.13 kPa), it can rise rapidly to very high levels. If the iCP increases beyond the mean arterial blood pressure (mAP), it will produce a hydrostatic blockage of cerebral perfusion, which can cause brain death in a few minutes.
II. Advances in the principles of craniocerebral injury treatment
The number of mild craniocerebral injuries is much higher than that of moderate and heavy ones, which still include some dangerous patients requiring neurosurgical management. 1993 stein and ross first proposed to further classify mild craniocerebral injuries into mild and light, with the aim of identifying patients with increased risk and giving effective management, which could reduce the serious resource burden for many countries.
(1) Mild patients: no loss of consciousness or amnesia, a gCS score of 15, normal mechanic response and memory, no focal neurological dysfunction, and no palpable depressed fractures. Generally, they can be allowed to go home after being informed about craniosynostosis precautions. However, the indications for hospitalization are: extra-cranial injury; very young or very old; no reliable caregiver at home; potentially serious medical conditions requiring treatment, etc.
(2) Mild patients have more than one of the following characteristics: brief loss of consciousness of less than 5 minutes; amnesia for accidents; a gCS score of 14; impaired motor response and memory; and palpable depressed fractures. A cT scan should be obtained promptly in any patient with a mild form. If no intracranial lesions are seen on the cT scan and there are no other indications for hospitalization, the patient may be allowed to go home after being advised about cranial injury precautions; if intracranial lesions are found on the cT scan or if there are other indications for hospitalization as described above, the patient should be promptly evaluated for surgery. In 1997, Hsiang et al., like others, further proposed to subdivide the originally considered mild craniosynostosis into two types: mild and high-risk mild craniosynostosis. In mild patients: a gCS of 15 and no fractures on cranial x-ray. High-risk mild craniocerebral injury: includes all patients with gCS scores of 13 and 14, as well as those with fractures on cranial x-ray in the gCS score of 15. Under this new classification, the former patients did not undergo any surgical management (including iCP monitor placement and cranial hematoma removal); whereas approximately 10% of the latter underwent surgery. It is more realistic to use x-ray to examine for skull fractures.
The goal of the initial treatment of severe traumatic brain injury is to combat regional or whole-brain ischemia. Reducing intracranial pressure and improving cerebral perfusion pressure (cPP) as well as cerebral blood flow (cBF) are important aspects of the treatment of craniocerebral injury. Treatment with barbiturates and moderate hypothermia under certain conditions and for a certain period of time can reduce brain metabolism, decrease cBF requirements, and reduce intracranial hypertension ( iCH), again an important complementary approach to the treatment of certain severe cranial injuries. Within 7 days of trauma, 140% of resting metabolic consumption should be provided for nonparalyzed patients and 100% for paralyzed patients, with 15% of calories being protein, either via gastrointestinal or non-gastrointestinal administration. The use of phenytoinamide and carbamazepine is effective in preventing early post-traumatic convulsions, but is not suitable as prophylactic treatment for late convulsions.
Third, heavy craniocerebral injury to improve cerebral blood flow to reduce cerebral ischemia treatment
It is now recognized that the establishment and adoption of a traumasystem is an important measure to reduce the mortality of heavy craniocerebral injury. Each traumasystem, which involves pre-hospital site, pre-hospital in-hospital transport, or (and) in-hospital iCU setting, is composed of specific treatment steps and methods that are considered to be the most reasonable at the time, based on research findings at the time. Each of these approaches is a specific manifestation of one aspect of the recently developed cPP management theory of craniocerebral injury described below. It is generally considered important to understand the steps in the systematic management of heavy craniocerebral injury through the knowledge of the trauma system at the time.
According to the Traumatic Coma Data Bank, the mortality rate of heavy craniocerebral injury has decreased from about 50% in the late 1970s to 36% recently due to the use of an “enhanced management program”. The pre-hospital “Advanced Life Support for Trauma”, the in-hospital “Guidelines for the management of severe cranial injury”, and the “European Brain Injury Consortium Guidelines for the management of adult severe cranial injury “These are typical of trauma systems. Although the content and focus of each of them are different, they all try to adopt practical solutions to ensure stable and adequate ventilation and circulation in order to prevent and control secondary brain damage. In each system, special emphasis is placed on early tracheal intubation, rapid transfer of the patient to a treatment unit in appropriate conditions, prompt and timely resuscitation, early cT scanning, timely removal of occupying lesions such as intracranial hematomas or contusions, and finally, extremely specific management within the iCU setting1.
Sedative and muscle relaxant medications, as well as ventilation, may be given to patients with severe craniocerebral injury during transport. Mannitol should not be routinely used prophylactically because of the risk of hypovolemia in hypotensive patients. Hyperventilation should also not be routinely used to reduce pCO2, which can exacerbate cerebral ischemia. However, hyperventilation and mannitol should be used at the onset of clinical signs of cerebellar herniation. It should also be noted that in patients with hypovolemic intracranial hypertension, mannitol should be used only if volumeresus-citation is adequate to prevent a sudden and dramatic drop in blood pressure.
iCP monitoring is now used to guide treatment in major craniocerebral injury treatment centers around the world and has become an integral part of critical care measures. The purpose of iCP monitoring has evolved in the treatment of severe craniosynostosis. Therapeutic attention during the period from 1977 to 1982 onward was almost exclusively focused on the management of iCH itself. Normal iCP is generally considered to be between 0 and 10 mmHg (0 and 136 mmH2O). Some authors consider the absolute upper limit of normal iCP to be 15, 20, or 25 mmHg, but most consider 20 mmHg to be “reasonable” and should be treated when iCP exceeds the upper limit. In practice, however, it is not possible to use a fixed domain value for the treatment of iCH in various situations, and the iCP should be interpreted with reference to clinical features and cT scans.
For example, in the presence of an intracranial occupying lesion, an iCP of 20 mmHg can cause herniation of the cerebellar curtain notch. However, in cases of diffuse brain swelling, iCP up to 30 mmHg can maintain adequate cerebral perfusion. Recent studies after 1990 have begun to emphasize the important role of cPP management. Determination of cPP ( cPP= iCP-MAP) based on iCP and blood pressure monitoring is one of the most important factors in ensuring cBF. Various methods to reduce iCP were used as necessary to improve cPP with the aim of improving cBF. rosner in 1993, based on the basic physiological and pathophysiological concepts necessary to understand the various phenomena of iCP, combined with the previous poiseuille’s law, re-qualified cBF as a function of cPP, vascular radius ( r) and blood viscosity ( n), with the relationship being cBF= cPP r4/ n.
The integrity or partial preservation of cerebrovascular autoregulatory mechanisms is a prerequisite for the use of cPP treatment protocols. The analysis of factors affecting cPP treatment is also an important theoretical basis for other treatments for heavy craniocerebral injury. There is an interaction between iCP, mAP, cPP, cBF and intracerebral blood volume. Because the cerebral vascular autoregulation curve shifts to the right after craniocerebral injury, increasing cPP can increase cBF in most cases, causing vasoconstriction and decreasing intracerebral blood volume to reduce iCP and improve cerebral ischemia. Moderate elevation of blood pressure or effective reduction of intracranial hypertension, or a combination of both, are important ways to increase cPP. In addition to increasing cBF and improving cerebral ischemia by elevating cPP, reducing blood viscosity and relieving vasospasm with drugs can be considered.
The previous classical cPP management protocols were based on the management of cerebral ischemia without dysfunction of cerebrovascular autoregulatory mechanisms after injury. This does not correspond to the actual situation, and further refinement requires accurate monitoring and management in terms of the functional state of cerebrovascular autoregulation, the identification of cerebral ischemia and cerebral congestion, and the degree of satisfaction of cerebral oxygen metabolism supply by cBF. Continuous and simultaneous multiparameter monitoring is important for early recognition and treatment of potentially harmful phenomena. The ideal monitoring should include several parameters of iCP, mAP, cPP, cBF, jugular venous oxygen saturation (sjO2) and arteriovenous oxygen difference (aVDO2), electroencephalographic activity, and transcranial Doppler (tCD). In underdeveloped countries and regions, at least iCP, mAP, cPP, and aVDO2 should also be monitored, and these are low-cost and easy-to-monitor techniques. The use of multiparametric monitoring allows accurate identification of whether the cause of iCH is cerebral ischemia or cerebral congestion. In a subset of patients monitored with partial impairment of cerebral vascular autoregulation, moderate adjustment of mean arterial blood pressure and the use of controlled hyperventilation can improve the vasoconstrictive effect and reduce iCP.
If the cBF after the above treatment still cannot meet the post-injury cerebral oxygen metabolism needs, measures to reduce cerebral oxygen metabolism can be considered to reduce the cBF demand, and on the other hand to ensure the appropriate relationship between cBF and cerebral oxygen metabolism rate demand, to reduce iCH cerebral protection purposes. According to statistics, 10% to 15% of hospitalized patients with severe craniocerebral injury, the use of conventional methods of lowering cranial pressure does not work, and the mortality rate is 84% to 100%. Sedative drugs are more useful for iCP elevation due to diffuse brain swelling, especially in children. When using isoproterenol or sodium thiopental, care must be taken not to bring about a greater drop in blood pressure that would have a negative effect on cPP.
It is now thought that there may be several mechanisms by which barbiturates act: alterations in vascular tone, inhibition of metabolism, and free radical-mediated lipid peroxidation. As the metabolic requirement decreases, so does cBF and its associated reduction in cerebral blood volume, which can have beneficial effects on both iCP and overall cerebral perfusion. In determining the dose and monitoring the effects of phenobarbital, observation of changes in EEG activity is more reliable than serum concentrations: the rate of cerebral oxygen metabolism is reduced by almost 50% when burst suppression ( burst suppression) is present in the EEG. Close monitoring and prompt management of hypotension is essential in the use of these drugs. Hypotension due to depressed myocardial contractility can be avoided by maintaining a normal intravascular volume.
The use of body cooling immediately after severe traumatic brain injury, with moderate hypothermia maintained for 24 hours, can reduce iCP and improve outcomes. The reasons for this effect are the reduction in inflammatory response after severe traumatic brain injury and the reduction in cerebral metabolism. It should be noted that the duration of this treatment, such as more than 48 hours, or temperature drop below 30 degrees, have increased the risk of infection and cardiac arrhythmia.
Fourth, the role of neuroprotective drugs in craniocerebral injury
The purpose of the use of many drugs is to exert an influence on the molecular, biochemical, cellular, and microvascular processes that occur during traumatic brain injury. However, evaluations of the effects of these agents now show that none of them are beneficial. In particular, it should be noted that corticosteroids, which are routinely used, have not improved patient outcomes even at high doses and are therefore no longer recommended. Calcium channel antagonists, glutamate receptor antagonists, and antioxidants, although shown to be effective in animal studies, have not been confirmed in clinical studies to date, probably because of inappropriate criteria for enrolling patients, etc.
V. Potential of gene therapy for craniosynostosis
Gene therapy for central nervous system injury is a new research direction. Animal studies have proved that various neurotrophic factors have therapeutic effects on the treatment of central nervous system injury. The use of transgenic technology to achieve therapeutic levels of CNS neurotrophic factor expression is another way to treat traumatic brain injury. The basic principles of gene therapy suitable for the treatment of craniocerebral injury are.
(1) The blood-brain barrier is open after injury, providing a specific therapeutic window for gene transfection.
(2) Traumatic brain injury, unlike genetic deficiency diseases, does not have to require persistent gene transfer. Recently, it has been found that the use of cationic microparticle-mediated transfer of neurotrophic factor genes has been considered as a potentially promising new therapeutic approach because, on the one hand, it does not carry the possibility of infecting the patient with viral diseases as in the case of virus-mediated gene transfer, and on the other hand, it overcomes the disadvantages of the previous inefficient transfection due to improved technology, etc.