Cerebral concussion in the monkey: an experimental model.

A statistically significant experimental model has been developed for reproducing head injury by impact in the monkey. Results with 80 monkeys subjected to occipital impact under specified conditions ( duration of phenomena, 1 to 10 milliseconds) enable the construction of curves relating the production of experimental cerebral concussion in 10, 50, and 90 percent of the monkeys to the average impulse of the blow in pounds-seconds, as well as to the average linear acceleration of the head. These curves are proposed as a baseline from which blows to various parts of the head, as well as nonimpacting impulsive loads, can be studied under various conditions of protection and according to varioucs time regimes.

Primate model for long-term study of intraventricularly or intrathecally administered drugs and intracranial pressure.

Meaningful pharmacokinetic investigations require animal systems which approximate the human situation. This report describes a primate model in which silicone catheters are placed into the fourth ventricle and the spinal subarachnoid space and connected to subcutaneous cerebrospinal fluid without tissue damage, prod, enables spinoventricular perfusion, and permits ventricular cerebrospinal fluid sampling over extended periods in unanethetized rhesus monkeys. This animal system may provide intraventricular pressure recordings and pharmacokinetic data similar to that obtained in man.

Massive cortical reorganization after sensory deafferentation in adult macaques.

After limited sensory deafferentations in adult primates, somatosensory cortical maps reorganize over a distance of 1 to 2 millimeters mediolaterally, that is, in the dimension along which different body parts are represented. This amount of reorganization was considered to be an upper limit imposed by the size of the projection zones of individual thalamocortical axons, which typically also extend a mediolateral distance of 1 to 2 millimeters. However, after extensive long-term deafferentations in adult primates, changes in cortical maps were found to be an order of magnitude greater than those previously described. These results show the need for a reevaluation of both the upper limit of cortical reorganization in adult primates and the mechanisms responsible for it.

A primate model for study of methotrexate pharmacokinetics in the central nervous system.

A new technique enabling repetitive sampling of cerebrospinal fluid (CSF) in unanesthetized rhesus monkeys was developed to study the pharmacokinetics of methotrexate (MTX) in the CSF. CSF and plasma MTX levels were monitored following intraventricular and intravenous MTX administration. CSF and plasma MTX disappearance curves in the monkey were virtually identical to curves generated in humans, suggesting that the mechanisms of transport between the CSF and plasma compartments are similar in both species. These observations validate this experimental primate model and indicate its potential application to the pharmacological study of CNS chemotherapeutic agents in man.

Granulomatous angiitis of the brain: a successfully treated case.

A patient with clinical and radiographic findings initially suggesting a neoplasm was diagnosed as having Hodgkin disease. Computerized axial tomography demonstrated profound diffuse decreased density similar to that seen in cases of cerebral edema or leukomalacia. Cerebral angiography showed blood vessels with a beaded appearance. A diagnosis of granulomatous angitis was made on the basis of brain biopsy specimens. Viral cultures were negative. Skin testing revealed poor response to antigens. The patient improved dramatically following a combination of radiotherapy and steroid therapy. Resolution of the low-density abnormally seen on serial EMI scanning and resolution of the vasculitis demonstrated in the post-therapy brain biopsy specimen was dramatic. This is the first case of granulomatous angitis of the brain diagnosed during life, and it points out the value of radiation and steroid therapy for relief of neurologic symptoms.

Head injury mechanisms and the concept of preventive management: a review and critical synthesis.

Recent advances in head injury research have produced a plethora of useful data coupled with a paucity of conceptual integration across the four ways in which this research is pursued. These research orientations are the epidemiological, biomechanical, basic neuroscientific, and clinicopathologic/therapeutic (including rehabilitation). This overview of the history and current state of the art assumes that biomechanics is the basic science of causation in head injury research and when fully integrated with its counterparts, physiology and pathology, it can serve to overcome our conceptual handicaps. A paradigm integrating biomechanics; into the sequence of preventive, protective, acute therapeutic, and rehabilitative interventions will be described as the concept of preventive management. From this we derive the hypothesized claim that the exact biomechanics and the physiopathologic response at the time of injury (at the macroscopic and microscopic levels) determine the sequence of so-called secondary effects that are conceived as the inexorable delayed manifestations of the primary events and concomitant boundary conditions. Knowledge of these events will enable accurate predictions of the natural history and outcome of head injuries from observations carried out in the early acute phase. Examples to test this claim will be given with particular reference to the two types of traumatic brain injury (TBI) phenomenologically associated with disturbances of consciousness, the onset of which can be either immediate or delayed. The current economics and availability of computational power provide a significant opportunity for the development of selected experimental, physical, and simulated models of head injury on the basis of which the complex neurovascular and nonneural cellular and fluid elements of the nervous system may be accurately modeled. This approach will significantly improve the efficiency and quality of the essential biological and clinical observations and model experiments required to validate the theoretical methods and their predictions.

Chronic ventricular cerebrospinal fluid sampling, drug injections, and pressure monitoring using subcutaneous reservoirs in monkeys.

Animal models enabling reliable access to ventricular cerebrospinal fluid (CSF) are crucial to the study of neuropharmacological and neurotoxicological effects of cytotoxic agents used to treat central nervous system neoplasms. This investigation concludes that 4th ventricular catheterization using subcutaneous CSF reservoirs in rhesus monkeys: (a) provides chronic access to sterile CSF without chronic immobilization, (b) enables mixing of injected drugs with lateral ventricular CSF, (c) permits sensitive monitoring of intraventricular pressure and (d) does not produce tissue damage during cannula implantation or breakdown of the blood-brain barrier.

Experimental intraoperative localization of retained intracerebral bone fragments using transdural ultrasound.

Precise intraoperative localization of retained bone fragments and foreign bodies avoids extensive brain disseciton, cerebral edema, damage to vital structures, incomplete debridement, and prolonged surgical procedures. Such localization after head trauma is often hampered by cerebral distortion, previous incomplete debridement, fragment migration, and surgical draping. Our intraoperative technique of transdural A-scanning using aspiration-biopsy transducers precisely localized 3.5-mm fragments without damage to underlying cortical tissue and vessles. Transdural A-mode echoencephalography was found to be more reliable for intracerebral depth estimations but epidural B-mode sonography was more useful for determining the size of fragments. Transdural ultrasound offered an intraoperative alternative to stereotaxic localization of retained bone fragments in experimental head trauma.

Role of vascular proliferation on angiographic appearance and encapsulation of experimental traumatic and metastatic brain abscesses.

Experimental traumatic abscesses were produced in rhesus monkeys by intracerebral injection of nutrient agar contaminated with Staphylococcus epidermidis, and metastatic abscesses were induced by intracarotid embolization of silicone cylinders contaminated with Staphylococcus epidermidis. All monkeys underwent preoperative and serial postoperative carotid angiography. Traumatic abscesses produced early capsular blushes and progressive anterior cerebral artery displacements. Metastatic abscesses induced transient midline shifts but no capsular stains. Postmortem studies on the monkeys showed that mean capsular thickness and segmental wall vascularity of the traumatic and metastatic abscesses were significantly different (p less than 0.001), despite equal abscess ages and similar abscess volumes. In comparison to traumatic abscesses, metastatic abscesses demonstrated reduced inflammatory cell infiltration and retarded collagen formation around proliferating capsular vessels. Brain surrounding the metastatic abscesses demonstrated ischemic changes. The results suggest that 1) capsular blushes during cerebral angiography are secondary to vascular proliferation within the capsule and not to compression of surrounding brain, 2) vascular staining reflects capsular thickness, 3) capsular vascularity contributes to collagen formation, 4) encapsulation is dependent upon the integrity of surrounding brain, and 5) adjacent cerebral ischemia may impede inflammatory responses involved in capsule formation.

Computerized axial tomography: estimation of spatial and density resolution capability.

The spatial and density resolution capability of the EMI-Scanner device for computerized axial tomography has been determined in vitro. For density differences greater than +/-1 per cent the spatial resolution is 6 X 6 mm. For density differences of 3 per cent and greater the resolution is 3 X 3 mm. Density resolution is at least +/-1 per cent for objects greater than 1 cm. Preliminary data on in vitro measurement of X-ray linear attenuation coefficients in tissue biopsies and standard solutions are given, together with the early results of enhancement of tissue density differences in vivo. Implications of this new technique for an in vivo neuropathology are suggested.

Motivation for traumatic brain injury rehabilitation questionnaire (MOT-Q): reliability, factor analysis, and relationship to MMPI-2 variables.

A Likert scale questionnaire was developed to assess motivation for postacute rehabilitation by traumatic brain injury patients. Items were designed to reflect head-injured individuals' statements about their attitudes toward head injury rehabilitation. Factors such as denial of illness, anger, compliance with treatment, and medical information seeking behavior were used to assess unfavorable and favorable components of motivation. Reliability was assessed using Cronbach's Alpha, which was found to be 0.91 for the total scale. Four factor analysis derived subscales were identified: Lack of Denial, Interest in Rehabilitation, Lack of Anger, and Reliance on Professional Help. Correlation and multiple regression analyses demonstrated moderate relationships between MOT-Q and several MMPI-2 variables largely related to indicators of somatic distress, depression and capacity for self-sufficiency. Lack of Denial subscale showed the strongest relationship to MMPI-2 of all MOT-Q variables, while Interest in Rehabilitation showed the best correlation to the MOT-Q total.