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Although palliative sedation therapy is often required in terminally ill cancer patients, its efficacy and safety are not sufficiently understood. The primary aims of this multicenter observational study were to 1) explore the efficacy and safety of palliative sedation therapy, and 2) identify the factors contributing to inadequate symptom relief and complications, using a prospective study design, clearly defined measurement methods, and a consecutive sample from 21 specialized palliative care units in Japan. A sample of 102 consecutive adult cancer patients who received continuous deep sedation were enrolled. Physicians prospectively evaluated the intensity of patient symptoms, communication capacity, respiratory rate, and complications related to sedation. Symptoms were measured on the Agitation Distress Scale, the Memorial Delirium Assessment Scale, and the ad hoc symptom severity scale (0 = no symptoms, 1 = mild and tolerable symptoms, 2 = intolerable symptoms for less than 15 minutes in the previous one hour, and 3 = intolerable symptoms continuing for more than 15 minutes in the previous one hour). Inadequate symptom relief was defined as presence of hyperactive delirium (item 9 of the Memorial Delirium Assessment Scaleor=2) or grade 2 or 3 symptom intensity 4 hours after sedation. The degree of communication capacity was measured on the Communication Capacity Scale. Palliative sedation therapy succeeded in symptom alleviation in 83% of the cases. Median time elapsed before patients initially had one continuous hour of deep sedation was 60 minutes, but 49% of the patients awakened once after falling into a deeply sedated state. The percentage of patients who were capable of explicit communication decreased from 40% before sedation to 7.1% 4 hours after sedation, and the mean Communication Capacity Score significantly decreased to the level of 15 points (P0.001). The respiratory rates did not significantly decrease after sedation (18 +/- 9.0 to 16 +/- 9.4/min, P = 0.62), but respiratory and/or circulatory suppression (respiratory rateor= 8/min, systolic blood pressureor= 60mHg, or 50% or more reduction) occurred in 20%, with fatal outcomes in 3.9%. There were no statistically significant differences in patient age, sex, performance status, target symptoms, or classes and initial dose of sedative medications between the patients with adequate and inadequate symptom relief. Respiratory and/or circulatory suppression was significantly more likely to occur in patients receiving sedation for delirium and those with higher levels on the Agitation Distress Scale. Higher dose of midazolam was significantly correlated with younger age, absence of icterus, pre-exposure to midazolam, and length of sedation. Palliative sedation therapy is effective and safe in the majority of terminally ill cancer patients with refractory symptoms. However, a small number of patients experience fatal complications related to sedation. Comparison studies of different sedation regimens are needed to determine the most effective and safe sedation protocol.

The purpose of this study was to quantitatively assess cardiovagal, adrenergic and postganglionic sudomotor functions in a patient with chorea-acanthocytosis. We describe a 25-year-old woman with acanthocytosis, lip and tongue biting, chorea like movements and increased levels of serum creatine phosphokinase. The patient presented with orthostatic hypotension. The heart period response to deep breathing was moderately decreased and the quantitative sudomotor axon reflex test (QSART) was mildly abnormal in the lower extremities. The composite autonomic score (CASS) for this patient was 6 points which indicates moderate autonomic failure. Although a few previous reports have described autonomic dysfunction associated with chorea-acanthocytosis and have indicated that impairment is primarily sympathetic, our case study suggests that there is also parasympathetic dysfunction. We conclude that there is widespread autonomic involvement in chorea-acanthocytosis and that autonomic studies are useful in monitoring their course.

An operative technique called the extensive transbasal approach is reported with the operative results of 11 cases. This is an operative mode in which en bloc osteotomy of the orbital roofs and frontal sinus is performed after ordinary bifrontal craniotomy. Through this approach, a far wider operative space than that afforded by conventional operative techniques is possible, and reconstruction of the frontal base can be made securely. We consider this approach of major clinical value.

Chronic fatigue syndrome (CFS) is characterized by persistent mental and physical fatigue for at least 6 months. Its pathophysiology is unknown and there is no proven effective treatment. We describe three cases who fulfill the criteria of CFS, in whom a defect of neuromuscular transmission and dysautonomia are present and who respond to acetylcholine-esterase inhibition. Case 1: 18-year-old female with a 3-year history of CFS. Response of compound-muscle-action potential, recorded using surface recording electrode, over left abductor pollicis brevis muscle, to repetitive nerve stimulation (RNS) at a rate of 10 Hz showed a 42% incremental response. Composite autonomic scoring system (CASS) showed mild cholinergic impairment (cardiovagal score: 1; sudomotor score: 2). Serological tests for Epstein-Barr virus (EBV) revealed positive antiviral capsid antigens (anti-VCA) immunoglobulins G (IgG). Oral pyridostigmine therapy (30 mg) resulted in marked improvement in symptoms. Case 2: 28-year-old female with 10-year history of CFS. RNS, using identical protocol, showed a 60% incremental response over the same muscle. CASS showed mild cholinergic impairment (cardiovagal score: 1; sudomotor score: 2) and this patient was also positive for EBV. This patient responded dramatically to 10-mg pyridostigmine. Case 3: 29-year-old female with a history of CFS for longer than 15 years. Repetitive stimulation, using identical paradigm to left abductor pollicis brevis muscle, showed a 42% incremental response. CASS showed mildly cholinergic impairment (cardiovagal score: 2; sudomotor score: 1). EBV antibody titers were positive. Patient responded to 30-mg pyridostigmine with an improvement in her fatigue. These three cases generate the hypothesis that the fatigue in some patients with clinical CFS might be due to a combination of mild neuromuscular transmission defect combined with cholinergic dysautonomia. Support for this thesis derives from the improvement with cholinesterase inhibition.

Intracranial dural cyst is a very rare congenital malformation. The presence of such a cyst was confirmed by means of computed tomography and magnetic resonance findings in a child with an enlargement of the head and developmental retardation and confirmed histologically in surgically obtained specimens of cyst wall.

✓ Lesions in the base of the frontal fossa have conventionally been approached extra- and intradurally through a bilateral frontal craniotomy. However, when the lesion is large or deeply situated, wider bilateral retraction of the frontal lobes is required to obtain a sufficiently large operative field. The authors describe a new operative approach for huge tumors at the frontal skull base, employing an en bloc bilateral osteotomy of the orbital roofs and frontal sinus. This procedure, which is a modification of the transbasal approach described by Derome and Guiot, is termed the “extensive transbasal approach.” The advantages of this technique over conventional operative approaches are described.

Even with the advent of antibiotics, treatment of postmeningitic hydrocephalus has been a difficult problem. Early surgical intervention based on new diagnostic modalities has improved mortality and morbidity. We reviewed 43 cases of postmeningitic hydrocephalus treated at our Institute over the past 20 years so that we could determine an effective therapeutic regimen. The subjects were 43 patients who had hydrocephalus following purulent meningitis. The results of our review were: 1. Thirty cases occurred during the first 10 years, while 13 occurred during the last 10 years, indicating a decline in the number of cases. 2. Meningitis was due to delayed treatment for myelomeningocele in 5 cases or encephalocele (1 case) 3. Complications such as brain abscess (4 cases) and subdural abscess (2 cases) or effusion (3 cases) were factors for poor prognoses. 4. Twenty five percent of the patients had multiloculated ventricular systems, resulting in a grave outcome. 5. Shunt operations should be postponed until ventricular fluid improves in accordance with these parameters: protein, less than 300 mg/dl, preferably less than 100 mg/dl; glucose, more than 30 mg/dl; cell counts, less than 200/3 cells per mm3. 6) Prognoses for the first 30 patients were poor, while those for the last 13 were improved. The present review indicates that early diagnosis and early treatment of meningitis are the keys to promising prognosis. Close communication with pediatricians is most important.

A variety of aromatic compounds with both activating and deactivating substituents were brominated with sodium monobromoisocyanurate (SMBI) 1, diethyl ether, diethyl ether–methanesulfonic acid, trifluoroacetic acid, or sulfuric acid were employed as solvents. Thus nitrobenzene was conveniently brominated in sulfuric acid, benzene was readily monobrominated in diethyl ether–methanesulfonic acid, and phenol was selectively brominated at the ortho position under mild conditions in refluxing diethyl ether. With substituents that are easily protonated, trifluoroacetic acid may be employed as solvent in the reaction with 1, in contrast NBS was ineffective in trifluoroacetic acid. This renders 1 a superior reagent relative to NBS. In addition to aromatics, alkenes, ketones and esters were also brominated with 1. Diethyl malonate was brominated with 1 and then subjected to a Bingel reaction with NaH to afford the desired methanofullerene in reasonable yield.

Cerebral autoregulation and vasomotor responsiveness to carbon dioxide were measured quantitatively in normal baboons and after intravertebral or intravenous of the beta-adrenergic blocking agent, propranolol hydrochloride (Inderal). Continuous measurements were made of cerebral blood flow (CBF: measured as bilateral internal jugular venous outflow using an electromagnetic flowmeter), cerebral perfusion pressure (CPP), arterial Po2 and Pco2 and venous Po2, cerebral arteriovenous oxygen difference and endotracheal Pco2. The autoregulation index (A.I. = deltaCBF/deltaCPP) and the chemical index (C.I.= deltaCBF/deltaPaco2), were used as quantitative measures.

Six cases of normal perssure hydrocephalus (NPH) were found among 160 surgical cases of intracranial hematoma due to severe head injury, in the past 10 years. Out of the 160 cases, 80 were followed up. The incidence of post-traumatic NPH was 3.7%, or 7.5% in the followed-up cases. After a little improvement following the removal of intracranial hematoma, these cases showed prolonged disturbance of consciousness or a delayed recovery rate and a progressive enlargement of the ventricle without cerebral atrophy on CT scan. Diagnosis of post-traumatic NPH was made by the plateau level of clinical improvement accompanied by absence of intracranial hypertension and a progressive ventricular dilatation shown by an increased bicaudate cerebroventricular index on CT scan. Radioisotope serum albumin cisternography revealed disturbance of cerebrospinal fluid (CSF) circulation in all these cases and was a reliable tool for determining the indication for a shunting operation, which brought a marked improvement in five patients. The authors believe that the shunting operation should be tried on post-traumatic NPH patients who do not show cerebral atrophy. Presence of a subarachnoidal and a contusional hemorrhage on brain surfaces, noted in the operation, suggests the need to pay attention not only to the disturbance of the conventional extracerebral CSF pathway, but to that of the intracerebral pathway as regards the pathogenesis of post-traumatic NPH.

The numbers of large and intermediate diameter myelinated fibers of 17 ventral lumbar (L3, L4 and L5) spinal roots (vsr) of man (ages 17-81 years) have been evaluated using the improved methods of histologic processing and morphometry now available, semi-automatic methods of measurement and programmed calculation and plotting. A population of small diameter myelinated fibers as found in thoracic (T11) vsr, which are presumed to be preganglionic sympathetic fibers, were essentially absent from L3, L4 and L5 roots. On the average, there were 5716 (70%) large diameter fibers and 2625 (30%) intermediate diameter fibers in the L3 ventral spinal root. Comparable figures for L4 vsr were 4900 (70%) and 2152 30%) and for L5 vsr were 5043 (75%) and 1559 (25%). On the assumption that these lumbar roots contain few if any small diameter myelinated pre-ganglionic sympathetic axons, the large diameter fibers correspond to alpha motoneuron axons and the small diameter fibers to gamma motoneuron axons. With age, a decrease in the number of myelinated fibers was estimated to be 350 fibers per decade (approximately 5% per decade).

A cell extract of Escherichia coli was found to contain a cytosine deaminase that can stoichiometrically deaminate 5-fluorocytosine to 5-fluorouracil. It was partially purified and aseptically encapsulated in semipermeable cellulose tubes. These capsules, each containing 0.20 U, were implanted under the skin of rats. After a month the capsules were taken out, and found to contain 0.025 ± 0.011 U per capsule (half-life of 10 ± 2 days) (mean ± S.D., n = 6). This fact provided us with an idea for a new approach to the chemotherapy of cancer with the combined use of 5-fluorocytosine administered orally and cytosine deaminase capsule implanted locally.

SUMMARY:The ultrastructural responses of cerebral tissue following temporary periods (½, 1, 2, 3, or 4 hour) of right, middle cerebral artery, (MCA) occlusion were studied acutely after a 3 day or 7 day interval following the removal of the MCA clip. Cortical and basal ganglia tissues for each ischemic duration were compared at 3 post-occlusive periods (acute, 3 days, 7 days).With the short periods of ischemic insult (½, 1, 2, 3, and 4 hour), the temporal and insular cortex contained no greater changes in the 7 day group than in the 3 day group.The basal ganglia were more susceptible to MCA occlusion as indicated by more marked cytological changes and/or necrosis in all intervals of ischemia.

The effect of multidisciplinary therapy is discussed, focusing on the results of the combined use and single use of intracarotid injection of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), fractionated irradiation by 60Co, and subcutaneous injection of OK-432 on brain tumor-bearing rats as well as on 31 human glioma cases. The experiments using brain tumor-bearing rats demonstrated the dose dependency of ACNU, and ACNU combined with 60Co irradiation resulted in an additive promoting effect, compared with the results of single use of each therapy. As for the mechanism of this effect, in addition to cell synchronization, the cell-killing effect of ACNU enforced by the circulatory disturbance due to irradiation was shown by the histological study. Multidisciplinary therapy for clinical cases, on the other hand, demonstrated good results among 60% of glioblastoma patients and 73% of benign astrocytoma patients, resulting in an improved survival rate. In in vivo study, OK-432 showed no cytocidal effect; however, OK-432 was an important agent for clinical use as it was effective in maintaining the general condition, or in reducing side effects induced by the combined use of ACNU and 60Co irradiation.

✓ Cerebral autoregulation and vasomotor responsiveness to carbon dioxide (CO2) were measured quantitatively by the use of the autoregulation index and chemical index, respectively, in normal baboons before and after intravertebral and intracarotid infusion of the anticholinesterase agent, neostigmine methylsulfate (Prostigmin). Continuous measurements were made of cerebral blood flow (measured as bilateral internal jugular venous outflow), arterial and cerebral venous pO2 and pCO2, cerebral arteriovenous oxygen differences, and endotracheal CO2. The effect of intravertebral infusion of neostigmine (12.5 µg/kg body weight) was compared to intracarotid infusion of neostigmine (25 µg/kg body weight) for assessment of any specific action of the drug on a hypothetical cholinergic vasomotor center, presumed to be located in the territory of the vertebrobasilar supply. No significant or persistent changes in cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) followed either intravertebral or intracarotid infusion of neostigmine. Cerebral vascular resistance (CVR) and cerebral perfusion pressure (CPP), however, decreased significantly after intravertebral infusion. Cerebral autoregulatory vasoconstriction during increases of CPP was significantly reduced following both intravertebral and intracarotid infusion. Cerebral autoregulatory vasodilatation was not altered as CPP was lowered. Cerebral vasodilatory reactivity to CO2 inhalation was significantly enhanced following intravertebral neostigmine but not following intracarotid neostigmine. Cerebral vasoconstrictive response to hyperventilation was not influenced by neostigmine. These results support the view that central cholinergic cerebrovascular influences exist, and are vasodilatory in nature.

Perivascular hemorrhagic lesions were produced in squirrel monkeys following transorbital occlusion of the middle cerebral artery. The respective periods of occlusive insult were 7.5, 15, 30 min, and 1 hr. After 1 wk of postoperative care, the animals were prepared for morphological study by a total body perfusion technique. Small hemorrhagic loci were observed grossly in the temporal cortex. By light microscopy these erythrocytic patches occupied predominantly a perivascular position, however, some interparenchymal clumps were also present. Ultrastructurally, separation of erythrocytes from the capillary components was noted. Interventing astrocytic end-feet were not swollen, nor did they show other morphological abnormalities (lysosomal increase, glycogen depletion, etc.). Capillaries were intact and ultrastructurally normal. Increased vacuolization was common in tissue adjacent to the erythrocyte clumps. Since no morphological changes were found in the microvasculature, it was concluded that diapedesis and extravasation had resulted from permeability changes in larger vessels.

The antifungal drug, 5-Fluorocytosine (5-FC) which is a derivative of 5-Fluorouracil (5-FU), lacks antineoplastic activity in human subjects because of the absence of cytosine deaminase (CDase) in mammalian cells. Therefore, intratumoral conversion of 5-FC to 5-FU by extrinsic CDase could be expected to induce antineoplastic effects at a local site with minimal systemic toxicity. The effects of combined administration of 5-FC and CDase in in vitro and in vivo were investigated. CDase was extracted from the E-Coli K-12 strain and purified. In vitro studies resulted in a significant inhibition of cell proliferation on cultured glioma cells (EA-285 cells) with 5-FC concentration over 10 μg/ml. Fluorocytographic studies of the tumor cell cycle progression showed synchronization in the early S phase at lower concentrations and complete blocking at the G1 and the early S phase with over 25 μg/ml. In in vivo studies, tissue concentrations of 5-FC and converted 5-FU were serially measured by a bioassay method after simultaneous intratumoral injection of CDase and systemic administration of 150 mg/kg of 5-FC to brain tumor bearing rats. The maximum concentrations of the drugs in the tumor tissue were 85 μg/g 5-FC at 1 hour and 9.6 μg/g 5-FU at 2 hours, which were sufficient to kill tumor cells. They were kept at higher levels in the tumor tissue than in the normal brain. In comparison, the maximum 5-FU concentration in the serum was only 0.4 μg/ml. The survival times and histological examinations of the experimental brain tumor models by this combined therapy were evaluated. The median survival time of the treated group was significantly prolonged (38.3 days) when compared with that of the control group (28.2 days). No side effects were recognized. Histological studies of the animal brains 2 weeks after the therapy revealed necrosis in the treated tumor. This combined treatment of 5-FC and CDase could be an ideal therapy for brain tumor in the future.

A 69-year-old male was admitted complaining of gait disturbances and diplopia, 2.5 years after an episode of serous meningitis. Neurological examination on admission disclosed Parinaud's sign, unsteady gait and dysdiadochokinesis on the left side. A striking finding on the computerized tomography (CT) was the left to right shift of the posterior portion of the third ventricle without visualization of the quadrigeminal and ambient cisterns, which were almost completely occupied by an isodense mass accompanied by high dense flecks and a low dense part. Enhanced CT showed positive enhancement in the vicinity of the pineal calcification. By the suboccipital supracerebellar approach, an encapsulated mass containing brownish yellow fluid was subtotally removed and a histological examination of it revealed epidermoid tissue and hemosiderin deposits in the solid portion. Few reports of isodense epidermoid cysts have so far been found in the literature giving a full explanation for this unusual CT attenuation value. Based on the clinical course and histology of this case, the pathogenesis of the unusual density is discussed along the following lines: The mixture of the low dense factor due to cholesterin and the high dense factor due to prior bleeding is believed to result in the isodense attenuation value in the liquid portion. Also, in the solid part, a microscopically mixed texture of deposited hemosiderin and cholesterin clefts in the inflammatory granulomatous tissue could explain its density on the CT scan.

✓ A case of multiple aneurysms is reported in which rupture of the internal carotid aneurysm occurred during carotid angiography, opacifying the subdural space. The patient recovered and was successfully treated by clipping of the aneurysm neck.

IN A REVIEW of the ultrastructual organization of human acidophil and chromophobe pituitary adenomas, the acidophils were from abundantly to sparsely supplied with secretory granules measuring 300 to 500 mμ, and the secretory granules in chromophobe adenomas were of two sizes, the average diameter being about 100 mμ in some cells and approximately 300 mμ in others. 1-3 Pituitary adenomas from 50 patients with acromegaly were subdivided by Young et al 4 into two groups designated as typical (6 cases) and atypical (44 cases) adenomas on the basis of staining with azure-eosin, PAS orange G, and Mallory Heidenhain methods. The atypical adenomas were composed of moderately or sparsely granulated acidophils and agranular cells that were indistinguishable from chromophobes. Herlant and his co-workers, 5-9 with the light microscope, studied the changes which occurred in the pituitaries of various animals during their reproductive cycles, and five functional classes of cells were differentiated in

Various classes of nuclear granules and inclusion bodies were observed in primary malignant lymphoma cells in the brain. In addition to the chromatin and the nucleoli, the perichromatin granules and the unusual dense granules were main granular structures. However, the most prominent features were clusters of interchromatin granules. The individual interchromatin granules were round or ovoid, sometimes filamentous in shape, and about 30 to 40 mμ in diameter. They were not extractable in enzyme digestion with pepsin, RNAase, or DNAase, and decreased markedly in electron density when both pepsin and RNAase were employed. It may be reasonably assumed that the interchromatin granules may be a complex of RNA and acidic proteins. Some nuclear bodies involved the interchromatin granules in formation. This study may suggest 2 possible processes of formation of nuclear bodies, which are derived (a) from the interchromatin substances or (b) from the inner nuclear membranes.

Die Wirkung des Augenschliessens und der Kopfrechnung auf Nystagmus wurde von uns untersucht.Wahrend der horizontaler pendelartiger Drehbewegung (Amp. 45 Period 5"), in normalen Fallen und derartigen mit zentraler Schadigung, Nystagmus wird durch der Augenschliessen gehemmt und these Hemmung tritt bei gleichzeitigen Kopfrechnung zuruck.Die Augenschliessen vergrossert den Kalorischen Nystagmus mehr in normalen Fallen und derartigen mit peripheren vestibularen Schadigungen, aber verkleinert in deren mit der zentraler Schadigungen.Spontan-und Lage-Nystagmus wird durch Augenschliessen gehemmt, bei zentraler Schadigungen (Z. B. Hirn Tumoren) aber nicht bei peripherer Schadigungen (Z. B. Menieresche Krankheiten).Gehemmter Nystagmus durch Augenschliessen erscheint bei Kopfrechnung ziemlich deutlich zu sein.Diese data gelten, um dem Herd, zentral oder peripher, zu diagnostieren.

To test whether congenital nemaline myopathy (NM) might have a neurogenic basis, we evaluated the number and frequency distribution of L5 motoneuron cell bodies and their myelinated ventral root (VSR) axons in a typical case. Results were compared to those from three age-matched controls and those from a child with Werdnig-Hoffmann disease (WHD). Diameter histograms of cell bodies of L5 motoneurons from controls contained three peaks which were identified as large, intermediate, and small cytons (LC, IC, and SC). In previous work from our laboratory, the numbers of LC and IC of the L5 segment was found to correspond closely enough to the numbers of LA and IA (large and intermediate diameter myelinated axons) of L5 ventral spinal root to indicate that the majority of LC are alpha and the majority of IC are gamma motoneurons. The number of LC of L5 reference cords varied from 3508 to 4916, and of IC from 967 to 2204. The diameter histogram of cytons from the NM case differed from controls; the LC and IC peaks were displaced to smaller diameter categories, but their number was normal (4520 and 2023, respectively). In WHD, the numbers of LC and IC were 211 and 946, respectively. Axons were similarly affected. The severe decrease from normal in the number of large motoneurons in WHD, and the reduction in size without loss of motoneurons in NM, indicates a different morphologic basis for NM and WHD. In NM the reduction in size without decrease in number of motoneurons is probably secondary to congenital myopathy and does not provide evidence for a neurogenic etiology.

Maffucci's syndrome is a rare, congenital mesodermal dysplasia combined with dyschondroplasia and haemangiomatosis, and there are only about 150 reported cases. This syndrome is often combined with other neoplasms. Our case was associated with goitre, enchondroma of the tuberculum sellae and pituitary adenoma; the latter brought about disturbance of vision. Including ours, four cases of Maffucci's syndrome associated with pituitary adenoma are found in the literature. In the case of Maffucci's syndrome, it is necessary to examine associated disease as well as associated pituitary adenoma and skull base enchondroma, similar to the correlation of von Recklinghausen's disease with acoustic neurinoma.

The diameter histograms of cell bodies (cytons) in motor neuron columns at the L5 segment of the spinal cord of adult man reproducibly yield three peaks of increasing height: small (Cs), intermediate (Ci), and large (Cl). Histograms of L5 myelinated axons obtained from the ventral root have two peaks of increasing height: intermediate (Ai) and large (Al). In histograms prepared from seven cases of amyotrophic lateral sclerosis (ALS), the Cl and Al peaks were decreased selectively and severely. This provides evidence for alpha, but not gamma, motor neuron vulnerability. The Cl peak of spinal ganglion neurons and the Al peak of dorsal roots were significantly reduced in number, without a concomitant increase in Ci, Cs, and Ai peaks. This, plus earlier reports of abnormal cutaneous sensation thresholds, abnormal rates of fiber degeneration in cutaneous nerves, and dorsal column demyelination, provides evidence that large afferent neurons are affected in ALS, but to a lesser degree than alpha motor neurons.

Three cases of acute epidural hematoma which developed on the opposite side during decompressive surgery for traumatic intracranial hematomas, such as, acute subdural hematoma, brain contusion or acute epidural hematoma, are presented. Each case had a skull fracture or a diastasis of the cranial suture contralateral to the decompressive craniotomy, which might have injured the dural artery. During or immediately after decompressive operations, sudden bulging of the brain was unexpectedly encountered. It was suspected that bleeding of the injured dural artery ensued from the abrupt release of the mass effect caused by the intracranial hematoma. Since deviation and distortion of the brain stem would be more rapid and more intense under such circumstances, operative evacuation of the contralateral epidural hematoma should be urgently carried out.

In recent morphometric studies of the cytons of lumbar motoneuron columns, it was possible to discriminate various populations by the criterion of size. It was felt that the use of celloidin embedding, optimal enlargement to increase the number of counting windows, and the use of improved morphometric analysis had been important to this discrimination. Employing the improved methods of histologic preparation and morphometry to a study of the L5 spinal ganglia of man, it has been possible to show tentatively that there are at least three populations of cytons by diameter. The average number of large, intermediate and small cytons were 11,429, 31,675, and 25,389 respectively. It should now be possible to test whether selective congenital absence or degeneration of any of these three populations of cell bodies is found in disorders affecting primary afferent neurons.

As compared to the diameter frequency distribution of myelinated fibers of L3, L4 and L5 ventral spinal roots (VSRs) which have two well developed peaks [large-diameter axons (AL) and intermediate-diameter axons (AI)] and a poorly developed or non-existent peak of small-diameter axons (AS), D11 VSRs contain small AL and AI peaks and a prominent AS peak. Because the ratio of AL to AI myelinated fibers of D11 VSRs is similar to that in L3, L4 and L5 VSRs and it is known that D11 VSRs contain many pre-ganglionic autonomic fibers it seems likely that AS is composed predominantly of preganglionic autonomic fibers. The mean diameter of the AS peak in D11 VSRs is approximately 2.4 micrometer. Average numbers of AS, AI and AL myelinated fibers for D11 VSRs are 3835, 738, and 1545 per root. These values should be useful as controls for morphometric studies of various neuropathies. The average diameter positions of the peak of AL, AI and AS of D11 VSRs as compared to those of L3, L4 and L5 are displaced to smaller diameter categoried which may reflect the smaller axon diameters of neurons which are shorter.

Sixty-two cases of acute subdural hematoma were clinically analyzed with special reference to such prognostic factors as age, Glasgow Coma Scale (GCS) score on admission, pupillary signs, decerebration, and initial computed tomography (CT) findings. Intraparenchymal lesions demonstrated by CT were evaluated according to Yamaura's classification. In 19 cases, serum fibrin and fibrinogen degradation products (FDP) were measured at the time of admission. Emergency surgery was performed in 46 cases, and the remaining 16 patients were treated conservatively. The final outcome was judged according to the Glasgow Outcome Scale, and patients were divided into a “good outcome” group (good recovery or moderate disability) and a “poor outcome” group (severe disability, vegetative state, or death). In general, the outcomes proved to be unsatisfactory. Forty-four patients (71%) had a poor outcome, with 32/62 (52%) mortality, and only 18 (29%) had a good outcome. The clinical factors associated with a poor outcome were age over 64 years, a GCS score on admission of less than 7, decerebration, and absence of pupillary reaction to light. Initial CT scans showed brain damage in 46 patients (74%), 39 (85%) of whom had a poor outcome. This indicates that the outcome was significantly related to brain injury complicating the acute subdural hematoma. A high serum FDP level was similarly related to a poor outcome, which suggests that the serum FDP level reflects the degree of both primary and secondary brain injury. Thus, measurement of serum FDP may be valuable both in assessing clinical status and in evaluating the extent of brain injury in acute subdural hematoma.

Few reports of metastatic Ewing's sarcoma encroaching on the central nervous system have been available, and two types of CNS involvement have been described; one is invasion of the skull and/or dura forming an extracerebral mass, and the other is intraparenchymal infiltration causing focal symptoms. A 12-year-old male received a ventriculo-peritoneal shunt operation because of non-communicating hydrocephalus brought about by a metastatic bony tumor on the occipital squama two years after the amputation of the right humerus as an initial treatment for the primary Ewing's sarcoma. After an eight month interval of remission, he underwent a revision of the shunt but still neurological condition worsened. The associated soft tissue mass around his nuchal region exhibited a tremendously rapid growth. Three months later, he died of compression of the brain stem by the metastatic bony tumor occupying the cisterna magna. Though the post-mortem examination showed the cerebellum apparently demarcated from the mass, histological survey verified some invasion at the cerebellar surface which had had direct contact with the mass.

Using a methodology which corrects for split cell error, and for the linear relationship between diameter of nucleolus and of cell body (cyton) and using semi-automatic methods of counting and sizing and programmed calculation and plotting, the number and diameter histograms of cytons of L-3, L-4, and L-5 motoneuron columns of 18 reference spinal cords of man (ages 17 to 82 years) have been evaluated. The number and frequency distribution of diameters (diameter histograms) of myelinated fibers of L-3, L-4 and L-5 ventral spinal roots (VSRs) had been determined in a preceding study as a control to validate the estimated number of alpha and gamma motoneuron cytons determined in this study from the same segment of spinal cord. The diameter histograms of cytons of motoneuron columns consistently contain three discrete peaks: a large-diameter peak (CL), an intermediate-diameter (CI) and small-diameter peak (CS). To illustrate, on the average, there were 4874 ± 585 large cytons and 1700 ± 564 ← intermediate cytons in the L5 segment of spinal cord. A reasonably close concordance was found between the average number of large cytons of spinal cord segments and the number of large-diameter myelinated fibers of ventral spinal roots (VSRs) (0.91, 0.94, and 0.98 for L3, L4 and L5 spinal cord segments and ventral spinal roots, respectively). For the ratio of the number of intermediate cytons to the number of intermediate axons the concordance was not as good (0.77, 0.85, and 1.14 for L3, L4 and L5 segments, respectively). Assuming that a cyton provides only one axon to VSR it is reasonable to infer from our studies that most large-diameter cytons are those of alpha motoneurons and that most of the intermediate-diameter cytons are those of gamma motor neurons. The greater number of axons than of cytons for the intermediate diameter group may be from a spurious inclusion of small-diameter axons (possibly pre-ganglionic autonomic fibers) with the intermediate-diameter group. On the average, the range of diameters of large-diameter cyton population in motoneuron columns was found to be 33 to 59 µm and for intermediate-diameter cytons was 24 to 33 µm. The total number of cytons per L3, L4 and L5 segments fell at a rate of ∽260, 175 and 200 per decade, respectively.

Cerebral autoregulation was studied in the baboon by increasing and decreasing cerebral perfusion pressure (CPP) before and after intravenous administration (1.5 mg per kilogram) of a long-acting alpha adrenergic blocker, phenoxybenzamine (PBZ). Likewise, cerebral vasomotor reactivity to changes of arterial carbon dioxide tension (Pa CO 2 ) was examined before and after PBZ. In order to permit quantitative analysis, cerebral autoregulation (A.I.) and chemical vasomotor reactivity (C.I.) were expressed as indices where A.I.=δCBF/δCPP and C.I.=δCBF/δPa CO 2 . Following the intravenous injection of PBZ, cerebral autoregulatory vasoconstriction was impaired as CPP was increased. Cerebral vasomotor reactivity to changes in Pa CO 2 was altered both during hyperventilation hypocapnia (HV) and hypercarbia induced by inhalation of 5% carbon dioxide if alterations of CPP brought about by these procedures were taken into consideration. During hypocapnia C.I. was reduced 30% and during hypercarbia C.I. was increased 10%. It is concluded that PBZ reduces the vasoconstrictor tonus of cerebral vessels during hypocapnia and raised CPP. It also enhances the vasodilator response to CO 2 inhalation.

Motor, spinal ganglion, intermediolateral and sympathetic trunk neurons were reconstructed by morphometric sampling of their cell bodies at L5 and T7 segments and at various levels of spinal roots and peripheral nerves in a 31-year-old patient with dysautonomia and compared to reference cases. The patient had strikingly fewer intermediate motoneuron column neurons and intermediate ventral root axons (probably gamma motoneurons), spinal ganglion neurons, preganglionic autonomic neurons and sympathetic trunk neurons that did controls (approximately 10--30% of reference values). The striking agreement between selective absence of intermediate-diameter cytons (Ci) and of intermediate diameter myelinated fibers (Ai), which are thought to be gamma efferent, of L5 motoneuron columns provides further confirmation to our previous suggestion that the Ci peak of motoneuron columns are somas of gamma efferent neurons. The number and size of alpha motoneuron cell bodies and their proximal axons were like those of controls but their distal axons were probably atrophic. This finding probably explains the small reduction in maximum conduction velocity of motor nerve fibers found in this disorder. The brunt of the pathologic process in this disorder has been borne by intermediate and small neurons preferentially.

Lesions in the frontal base have been conventionally approached extra- and intradurally through a bilateral frontal craniotomy. However, when the lesion is large or deeply situated, wider retraction of the bilateral frontal lobes is required to obtain a sufficient operative field. The authors describe a new operative approach to dumbbell-shaped tumors in the frontal base, consisting of en bloc osteotomy of the bilateral orbital roofs and frontal sinus. This procedure, which is a modification of the transbasal approach described by Derome, is termed the "extensive transbasal approach." Successful applications of this procedure in three patients with frontal base tumors, two with frontal base fractures, one with a frontal arteriovenous malformation, and one with a frontal sinus mucocele are described. Also, the advantages of this approach over other, conventional operative approaches are discussed.

Morphometric assessment of the size distribution of cell bodies (cytons) in motor neuron columns from serial sections of lumbar spinal segments reproducibly yields three peaks. Using troughs between peaks as division points, it is possible to determine the number of large (Cl), intermediate (Ci), and small (Cs) cytons per lumbar segment. In a patient with above-knee amputation 4 1/2 years previously, the number of Cl was 42%, Ci 99%, and Cs 129% that of normal. Nine years after total amputation of a lower limb for chondrosarcoma, a second patient exhibited values of 25%, 14%, and 55%, respectively. Normal results were obtained from the non-amputated sides. These results, and our previous studies on the permanent axotomy model, show that loss of target tissue by axotomy leads to atrophy and then loss of motor neurons. Extrapolated to the interpretation of morphologic abnormalities of proximal neuronal alterations in peripheral neuropathy, these results suggest that atrophy and loss of such proximal elements cannot be explained by acute distal pathology, but could be the result of chronic disorders, particularly when severe.