Jack Jallo

Clinical Trials in Head Injury

Secondary brain damage, following severe head injury is considered to be a major cause for bad outcome. Impressive reductions of the extent of brain damage in experimental studies have raised high expectations for cerebral neuroprotective treatment, in the clinic. Therefore multiple compounds were and are being evaluated in trials. In this review we discuss the pathomechanisms of traumatic brain damage, based upon their clinical importance. The role of hypothermia, mannitol, barbiturates, steroids, free radical scavengers, arachidonic acid inhibitors, calcium channel blockers, N-methyl-D-aspartate (NMDA) antagonists, and potassium channel blockers, will be discussed. The importance of a uniform strategic approach for evaluation of potentially interesting new compounds in clinical trials, to ameliorate outcome in patients with severe head injury, is proposed. To achieve this goal, two nonprofit organizations were founded: the European Brain Injury Consortium (EBIC) and the American Brain Injury Consortium (ABIC). Their aim lies in conducting better clinical trials, which incorporate lessons learned from previous trials, such that the succession of negative, or incomplete studies, as performed in previous years, will cease.

CB2 receptor activation attenuates microcirculatory dysfunction during cerebral ischemic/reperfusion injury

Previous studies from our laboratory indicated that selective cannabinoid CB(2) agonists were able to attenuate cerebral ischemia/reperfusion (I/R) injury. The goal of current study is to further test whether this attenuation involves cerebral microcirculatory function during I/R injury. Middle cerebral artery occlusion with reperfusion (MCAO/R) was performed in male mice. A selective CB(2) agonist was administered at different dosages and different times. Cerebral infarction volume, neurological function and cerebral microcirculatory function (leukocyte/endothelial interactions, cell adhesion molecule expression and blood-brain barrier disruption) were examined in vivo and in vitro. CB(2) knockout mice were subjected to MCAO/R following same procedures. Administration of the CB(2) agonist at middle dosage exerted optimal effects in reducing cerebral infarction and improving neurological function compared with other dosage groups and control group. Treatment with the CB(2) agonist at the optimal dose was still effective when given 3 h after MCAO. Transient ischemia significantly increased leukocyte/endothelial interactions, adhesion molecules expression and blood-brain barrier disruption which were all attenuated by pre-treatment with a CB(2) agonist. CB(2) knockout mice showed larger cerebral infarction and worse neurological function compared to wide type. In conclusion, CB(2) activation contributed to protecting the brain through the attenuation of cerebral microcirculatory dysfunction during cerebral I/R injury.

Hypertonic saline: a clinical review

Literature suggest that hypertonic saline (HTS) solution with sodium chloride concentration greater than the physiologic 0.9% can be useful in controlling elevated intracranial pressure (ICP) and as a resuscitative agent in multiple settings including traumatic brain injury (TBI). In this review, we discuss HTS mechanisms of action, adverse effects, and current clinical studies. Studies show that HTS administered during the resuscitation of patients with a TBI improves neurological outcome. HTS also has positive effects on elevated ICP from multiple etiologies, and for shock resuscitation. However, a prospective randomized Australian study using an aggressive resuscitation protocol in trauma patients showed no difference in amount of fluids administered during prehospital resuscitation, and no differences in ICP control or neurological outcome. The role of HTS in prehospital resuscitation is yet to be determined. The most important factor in improving outcomes may be prevention of hypotension and preservation of cerebral blood flow. In regards to control of elevated ICP during the inpatient course, HTS appears safe and effective. Although clinicians currently use HTS with some success, significant questions remain as to the dose and manner of HTS infusion. Direct protocol comparisons should be performed to improve and standardize patient care.

Diagnosis and Management of Occipital Condyle Fractures

The authors recently treated three cases involving fractures of the occipital condyle. First described by Bell in 1817, this lesion has proven to be very rare, with only 32 cases previously reported in the literature. Plain films often do not reveal any abnormality, making diagnosis difficult. High-resolution computed tomography has been demonstrated to be very sensitive in diagnosing this lesion. This fact was borne out in the authors series. All of the authors patients were managed either with a Philadelphia collar or with halo fixation, with excellent outcomes.

An investigation of cerebral edema and injury volume assessments for controlled cortical impact injury.

UNLABELLEDnUsing the controlled cortical impact (CCI) model, our laboratory compared edema in contralateral and ipsilateral regions to help clarify conflicting reports of contralateral edema and for enhanced assessment and interpretation of CCI injury pathophysiology. This investigation examined regional edema in response to graded injury severities over time with regards to tissue damage. Prior to injury rats were anesthetized with ketamine and xylazine (1:1). CCI injury parameters were set at 4.0m/s and 120 to 130 ms. Rats were randomized to receive moderate or severe injuries set at 2.0 and 3.0mm depths, respectively. Cerebral edema and injury volume were examined separately following euthanasia with pentobarbital. Cerebral edema was measured using the wet-dry weight technique at 24 or 48 h after injury. Sham animals underwent all surgical procedures except the impact injury. Injury volume was quantified using 2,3,5-triphenyltetrazolium chloride staining at 24h or 7 days after injury. The results of this investigation confirm that cerebral edema is absent in the uninjured, contralateral hemisphere after moderate and severe CCI injury. There were regional differences in cerebral edema formation in the hemisphere ipsilateral to injury that were dependent on injury severity and the length of time after injury. Tissue damage was reduced over 7 days following moderate CCI injury.nnnCONCLUSIONSn(1) the absence of edema in the contralateral hemisphere allows it to serve as a valid control for edema formation, (2) misrepresenting injury volume because of edema continues to be a problem for evaluating CCI injury and treatment efficacy, and (3) reduced injury volume over 7 days following CCI injury suggests tissue recovery after initial dysfunction.

Chordoma: A case report

BACKGROUNDnChordomas are tumors of notochordal origin that account for approximately 1%-4% of all primary malignant bone tumors. The majority of patients with chordomas have a poor surgical prognosis due to extent of disease at diagnosis. These lesions have been previously classified based solely on their location.nnnMETHODSnWe describe here a case report of a posterior epidural C5-T1 chordoma that was discovered in a young patient who presented with weakness and paresthesia in all four extremities. This lesion was notable for its extraosseous and extradural characteristics.nnnRESULTSnC5-T1 laminectomy with gross total resection of the mass led to complete resolution of all symptoms. There has been no evidence of tumor recurrence to date.nnnCONCLUSIONSnWe propose here a new classification system for chordomas that emphasizes the difference in resectability of these lesions depending on the space they occupy and the presence or absence of an osseous connection.

Cerebral Syrinx with Chiari I Malformation

A 13-year-old female presented with acute left gaze paralysis. MRI revealed hydrosyringomyelia (HSM) with syringobulbia in the left pons extending cephalad into the centrum semiovale. A suboccipital craniotomy was performed and the foramen of Magendie was imperforate. Ocular movements normalized in 2 months and postoperative MRI confirmed resolution of the cerebral syrinx and syringobulbia and diminished HSM. This case represents an extreme example of the altered spinal fluid dynamics with Chiari I malformation. Theories on HSM are reviewed.

A chronic model to simultaneously measure intracranial pressure, cerebral blood flow, and study the pial microvasculature

In an effort to study changes in cerebral blood flow (CBF), intracranial pressure (ICP) and intracranial compliance (ICC) simultaneously, we have developed a chronic model in rats using a pial window crown with two ports. This model can also be used to study vasoreactivity of pial vessels. Female Sprague-Dawley rats weighing between 225-250 g underwent placement of cranial chamber with dual ports under pentobarbital anesthesia. To test the utility of this technique 45 groups of rats were studied. Group 1 consisted of control animals. Group 2 consisted of rats undergoing 15 min of global cerebral ischemia. Rats in group 3 were evaluated for changes in vessel diameter and ICP after adenosine injection. In group 4 leukocyte/endothelial interactions were evaluated. These groups demonstrate the ability of this model to monitor CBF, ICP, ICC and pial vessel architecture in chronic rat experiments.