A morphological study was performed on the nerve fibers and the smooth muscle of the cerebral arteries in human brains with hypertensive intracerebral hematomas. In addition, an experimental study was also performed on dogs. Immediately after autopsy, the nerve fibers on the Willis circle and its main branches in five patients with hypertensive intracerebral hematomas were examined with Falck and Hillarp's fluorescent method and with Koelle's thiocholine method. The smooth muscle of the main cerebral arteries from ten brains with intracerebral hematomas, which had been preserved in 10% formalin, was studied with histochemical examinations. Bilateral hypothalamic lesions were made experimentally in 16 dogs, and the nerve fibers and the smooth muscle of the main cerebral arteries were examined by the histochemical method and with an electron-microscope. No adrenergic fibers were seen with the fluorescent method in any of the five patients. The cholinergic nerve fibers on the same arteries were observed with the thiocholine method. Examinations for cholinergic nerve fibers of arteries from the affected cerebral hemispheres of two patients did not show any enzymatic activity, while it was shown to be present in the intact hemisphere. Ten brains showed degeneration of the smooth muscle cells in the tunica media. Animal studies showed a decrease of the adrenergic and cholinergic nerve fibers from experimental hypothalamic injuries. The degeneration of the nerve fibers was observed with electron-microscopic examinations. Thus our findings in this study suggest that brain stem damage leads to the degeneration of the smooth muscle together with the adrenergic and cholinergic nerve fibers of the cerebral artery.
Two endocrine functions, HGH synthesis and release, were separately studied on human chromophobe adenomas, isolating the hormone with polyacrylamide gel disc electrophoresis after in vitro labelling of the hormone with 14C-leucine. The results of the experiments utilizing fresh adenoma tissues obtained from 8 cases at operation revealed that all of the adenomas synthesized and released HGH. Employing appropriate parameters, HGH synthesis and release functions of the tumor were estimated. HGH synthesis function was likely to be extremely low, but the release function rather high. HGH content in the adenoma tissues ranged from 0.04 to 2.56 ng/mg wet tissue, which was exceedingly smaller than the value of 8000 ng/mg wet tissue observed with the human anterior pituitary obtained at autopsy.
Tissue culture of 20 pituitary adenomas (four acromegalies, 15 non-functioning tumors, one Forbes-Albright syndrome) was performed with the Maxmow double cover glass assembly. Growth hormone and prolactin in the medium were measured during the culture. Morphological feature in vitro was also compared with that of the original tumor. In chromophobe adenomas of clinically non-functioning, tumor cells had round secretory granules of not only 100, but also 300 mμ in diameter. The study of their tissue culture revealed that these tumor cells were secreting growth hormone in all the cases. In acromegalic patients, the culture medium a month later still contained more than 1000 ng/ml of growth hormone and also many secretory granules remained in the cultured cells. Thus, it was suspected that the tumor cells in acromegalic patients had autonomous secretory functions of growth hormone. In pituitary adenomas of Forbes-Albright syndrome and even non-functioning or acromegaly, prolactin secretion from tumor cells was demonstrated. Ovoid, ellipsoid, or irregular secretory granules of 500 to 1000 mμ in acromegalic patients and 150 to 500 mμ in the other cases were observed with an electron microscope.
Astroprotein, an astrocyte-specific cerebroprotein, in cerebrospinal fluid (CSF) and cyst fluid of tumors from 20 patients with brain tumors as well as other diseases has been measured by radioimmunoassay, and the following results were obtained: 1) Remarkably great amounts of astroprotein were detected in both CSF and cyst fluid of tumor from patients with glioblastoma. 2) Astroprotein in CSF from patients with brain tumors originated from other than astrocyte was found increased when the tumor was huge and was accompanied with severe fibrous gliosis. 3) Astroprotein in CSF from patients with other diseases than brain tumors was found generally minimal.
It is a well-known fact that damage to a cell induces activation of lysosomes. This phenomenon subsequently leads to “autofagy” and “heterofagy, ” which are typical functions of lysosomal enzymes. Some reports state that lysosomal enzymes are highly activated also during cellular division and multiplication. Furthermore, it has been verified that the enzymes retain by far a higher activity in malignant tumor cells. A recent report indicated that cyclic AMP supports morphologically cultured glial cells and glioma tissues toward their differentiation and further toward normalization. Based on these reports, it was the object of this study to examine the effect of cyclic AMP on lysosomal enzyme activities during cellular multiplication. In the acute stage, within one week from injury infliction, β-glucuronidase and acid-phosphatase increased activities conspicuously and reached their respective peaks on the 5th day after injury. The glial cell, being induced by the high enzyme activity, showed active cellular division and multiplication starting from the 5th day on. Although elevation of activity was clearly observed at this stage, the enzyme activity showed little difference during the period of gliosis formation, when division and multiplication settled. Human glioma tissues retained a level of activity several times higher. Administration of dibutyryl cyclic AMP in situ produced significant inhibitory tendency on the enzyme activity, resulting in impediment of multiplication. The rise in enzyme activity after cellular damage and along with cellular division were directly reflected in the cerebrospinal fluid, which might be utilized in diagnosing the extent of intracranial disorders, effectiveness of treatment and prognosis.
The relationship between initial subarachnoid hemorrhage due to an aneurysm rupture and reattacks due to either rerupture or infarction within one month was analysed in 52 cases, with special reference to the severity of the initial attack and the time intervals in between. Differences in the type and time of reattacks depend upon the severity of the initial bleeding: initial bleedings associated with unconsciousness were overwhelmingly followed by infarction occurring exclusively at 4-14 days, whereas rebleeding occurred only within the first three days or after the 15th day. Initial bleedings unassociated with unconsciousness were followed by rebleeding occurring rather at random intervals. These observations may be helpful in deciding the best treatment for ruptured intracranial aneurysms in the acute stage.
The authors report a series of 11 cases of ruptured intracranial aneurysms followed by cerebral vasospasm manifesting neurological deficits. These patients were treated by cervical sympathectomy consisting of perivascular sympathectomy of the cervical internal carotid artery and superior cervical ganglionectomy on the same side as the cerebral angiospasm. Improvement of symptoms was observed following 13 procedures in 11 patients, within 10 hours in four cases, on the next day in five cases, and by the seventh day in two cases. In the remaining two cases no beneficial effect was observed. This technique was most valuable when it was done immediately after the appearance of the symptoms of infarction, before the development of irreversible brain damage.
Fibrin and fibrinogen degradation products (FDP) were examined in 30 cases of chronic subdural hematoma. Fibrinogen was not found in the contents of subdural hematoma in 29 cases, and only a small amount of fibrinogen was detected in the remaining case. The liquefied hematoma content was not coagulated by the addition of thrombin. Early FDP were present in one third of the cases in which paracoagulation tests were positive. Immunoelectrophoresis of hematoma demonstrated precipitation with anti-human fibrinogen serum, anti-FDP-D serum and anti-FDP-E serum. The amount of FDP in hematoma was 10.0 to 10500 μg/ml by hemagglutination-inhibition immunoassay, whereas FDP values were in the normal range in other body fluids, such as serum, cerebrospinal fluid and urine. These results indicate an increased local fibrinolytic activity in chronic subdural hematoma. It is also presumed that local hyperfibrinolysis plays an important role in the etiology of chronic subdural hematoma.
The present experiment was undertaken to clarify the pathogenesis of primary fatal head injury due to impact and further to obtain a severity index denoting the relationship between the magnitude of impact and the severity of head injury in animals with experimental blunt head injuries caused by simplified impact upon the cranium. The experiment was conducted on Ketalar-anesthesized rhesus monkeys. Impact was imparted to the animals by means of a 12 in. HYGE impact tester. Before and after the impact the animals were subjected to a series of examinations at intervals, including respiration, ECG, blood pressure, cerebral circulation, partial pressure of blood gases, acid-base equilibrium and EEG. Pathological examination, measurements of lactic acid and monoamine contents in various portions of the brain were also made. An impact upon the head, at an acceleration in the horizontal antero-posterior direction of 1000-1500 G and a duration of 3-4 msec, proved fatal invariably in animals weighing more than 8 kg (body weight×effective acceleration above 30 kg). In dead animals, primary injury consisting of narrowing of lumen and stoppage of blood flow in perforating arteries of the brain-stem and small hemorrhages in the same areas was noted. It was demonstrated that these changes give rise to central dysregulation of the circulatory (including heart) and respiratory systems which in turn acts on cerebral circulation and metabolism. This fact not only proves the existence of a primary fatal head injury and further clarifies its mechanism of development but also suggests the possibility of grading the severity of head injury by simplified impact and also by expressing the relationship between the magnitude of impact and the severity of brain damage as a severity index.
Factors affecting prognosis of coma following various brain damages were studied on 567 patients who were “unconscious” upon admission to the Trauma Intensive Care Unit of Osaka University Hospital. The total consisted of 313 head injuries, 83 cerebrovascular diseases, 143 carbon monoxide poisonings and 28 post cardiac arrests. Time courses of recovery from unconsciousness were compared from the etiology of brain lesions. And then, in the head-injured patients, age and neurological signs and cerebral metabolic parameters in acute stage were investigated in relation to their outcomes. The conclusions are as follows: 1) Some differences in recovery rates of unconsciousness were observed from the nature of lesions. No recovery after one week's unconsciousness was noted in cases of both cardiac arrest and carbon monoxide poisoning patients. On the other hand, some patients with head injuries or cerebrovascular diseases regained consciousness even after one month of coma. 2) While pupillary abnormalities and decerebrate rigidity in adult patients following head injury promise prolonged unconsciousness or subsequent brain death, they do not always indicate fatal outcome or permanent disability in younger patients. 3) Long lasting decerebrate rigidity and hypocarbia are clues to “vegetative” survival. 4) CSF acidosis and jugular hyperoxia in acute stage are poor prognostic signs.
We reported the results of visually evoked potential (VEP) and somatosensory evoked potential (SEP) examinations in 10 patients in the vegetative state and 20 patients in the coma state following acute serious brain damages. Variable behaviors of average VEP and SEP in vegetative state were divided into four groups, Group I, had a marked suppression or absence of VEP and SEP simultaniously (20%). Group II had a suppression or absence of VEP with a near-normal SEP (20%). Group III had a suppression or absence of SEP with a near-normal VEP (30%). Group IV had a near-normal VEP and SEP respectively (30 %). On the other hand, all of 20 patients with acute disturbed consiousness of delta coma had a marked suppression or absence of each component of average VEP and SEP. Concerning the prognoses of cases of acute serious brain damages, those who had recovered from VEP and SEP within three or four weeks after the serious brain damage, did not fall into the vegetative state. Even when patients had fallen into the vegetative state for about four months, in cases where recoveries of VEP and SEP were observed antecedent to those of EEG, they managed to be free from falling into a permanent vegetative state. Based on these results, it is concluded that clinical study of VEP and SEP in the vegetative state or the acute coma state could be a useful diagnostic aid to predict the prognoses of these vegetative patients.
Thirty adult dogs were subjected to immobilization of the spinal cord under nembutal anesthesia to produce spinal cord injury of two different degrees of severity by means of an impact of 500 G.cm or more and 300 G.cm or less respectively. In one group of animals an assessment was made of the resultant disturbance of spinal cord circulation at its acute stage while registering the serotonin content of the injured segment of the spinal cord as well as the evoked spinal cord potentials in response to peripheral nerve stimulation. The other group underwent local spinal cord cooling (1000 ml/hr.) for a comparison with the nontreated group of the ensuing changes in the circulatory disturbance of the spinal cord. As a result, it was found that the impact on the spinal cord, because of the anatomical constitution of the spinal arteries and veins as well as the specific features of spinal cord circulation, gave rise to rupture of microvessels in the central gray substance along with petechial hemorrhage, which in turn led to elevated serotonin level in the injured area, and that these two phenomena were responsible for the subsequent deterioration of spinal cord circulation with increased central necrosis. It was shown that the local cooling method is effective in ameliorating microcirculation and correcting the metabolic acidosis due to the impact and also in inhibiting the formation of serotonin which acts adversely in these respects.
Two cases of the severe fracture-dislocation of the cervical spine with tetraplegia have been treated successfully with a new technique. This technique consists of anterior vertebral body fusion with a tibia span added to the Cloward's method. This procedure permitted substantial removal of ruptured disks and bone fragments, effectivelly strengthened the spine weakened by fracture, and also enabled early start to a postoperative rehabilitation program. It seems that fracture-dislocation of the cervical spine should be treated operatively as early as possible.