The evaluation of brain CBF and mitochondrial function by a fiber optic tissue spectroscope in neurosurgical patients.

The brain of neurosurgical patients are exposed to various manipulations in the ICU or during surgery. Under such conditions brain O2 balance may become negative and as a result brain vitality and function will deteriorate. In order to evaluate brain vitality in real time it is important to measure more than one parameter. The multiparametric monitoring system used in our previous study to monitor comatose patients (Mayevsky et al., Brain Res. 740: 268-274, 1996) was changed into a "simplified" tissue spectroscope for real time monitoring of brain O2 balance. Mitochondrial function was evaluated by monitoring the NADH redox state by surface fluorometry. Microcirculatory blood flow was assessed by laser Doppler flowmetry. The combined optical probe was located on the surface of the brain during various neurosurgical procedures and the responses were recorded and presented in real time to the surgeon. A total of 32 patients were monitored during various procedures. The results could be summarized as follows: 1. Hypercapnia led to 3 different types of responses. In two patients the 'stealing' like event was recorded. In the other 7 patients the responses to high CO2 was not detectable. In the last group of 6 patients a clear CBF elevation was recorded with variable response of mitochondrial NADH. 2. Our monitoring device was able to evaluate the efficacy of the STA-MCA anastomosis during aneurysm surgery. 3. A significant correlation was recorded between CBF and NADH redox state during changes in blood pressure, papaverine injection, spontaneous drop in blood supply to the brain or during releasing of high ICP levels. We conclude that in order to evaluate the metabolic state of the brain during neurosurgical procedures it is necessary to monitor both CBF and mitochondrial NADH by using the tissue spectroscope.

Combined beta FSH and beta LH response to TRH in patients with clinically non-functioning pituitary adenomas.

OBJECTIVE: 'Paradoxical' responses of LH, FSH, alpha-subunits and beta LH to TRH have previously been reported in individuals with clinically non-functioning pituitary tumours (NFT). The present study was designed to assess the in vivo and in vitro responses of beta FSH to TRH in NFT. We further examined the possibility that a TRH challenge with combined measurement of beta FSH and beta LH will identify a common anomalous secretory pattern in patients with NFT. DESIGN, PATIENTS AND MEASUREMENTS: Forty patients with NFT underwent a standard TRH test (400 micrograms intravenously). Blood samples for the determination of beta FSH, beta LH, FSH and LH were collected prior to TRH as well as 15, 30, 45, 60 and 90 minutes following injection. Additionally, cultured adenomatous cells from eight to these patients were exposed to TRH in the absence and presence of octreotide and gonadotropin subunits were determined. RESULTS: TRH elicited a marked rise in circulating beta FSH in 29 of 40 individuals and in beta LH in 28 of 36 patients with NFT. In a subgroup of eight individuals whose tumours were harvested during surgery and cultured for 7-21 days, TRH increased beta FSH or beta LH and alpha-subunit release in cultured adenomatous cells in all cases, including tumours from subjects not responding to TRH in vivo. In this subgroup of patients octreotide inhibited basal beta FSH secretion but not basal beta LH secretion both in vivo and in primary cultures of NFT cells. Both the in vivo and in vitro beta FSH, beta LH and alpha-subunit responses to TRH were entirely inhibited by octreotide. In all, 38 of the 40 subjects could be identified by either elevated basal beta FSH or beta LH levels and/or an abnormal rise in either beta FSH or beta LH in response to TRH. CONCLUSION: The measurement of basal and TRH-stimulated beta-FSH and beta-LH levels identifies an abnormal hormonal secretory pattern in the vast majority (> 90%) of patients with clinically nonfunctioning pituitary tumours.

Relative sparing of anterior pituitary function in patients with growth hormone-secreting macroadenomas: comparison with nonfunctioning macroadenomas.

Pre- and postoperative anterior pituitary function was assessed in 26 subjects with nonfunctioning macroadenoma (NFMA) and in 15 acromegalic subjects with macroadenomas. Preoperatively, NFMA patients had a higher prevalence of secondary hypogonadism (78% vs. 40%; P < 0.05), hypothyroidism (23% vs. 0%; P = 0.06), and hypoadrenalism (43% vs. 7%; P = 0.02) compared to individuals with GH-secreting macroadenoma (GHMA). Patients with NFMA also had a higher prevalence of more severe pituitary failure compared with acromegalic patients; 56% of the patients in this group had more than one pituitary hormone axis impaired compared to only 8% in the acromegalic group. These differences could not be accounted for by tumor grade and/or stage. Transsphenoidal pituitary surgery led to a significant improvement in anterior pituitary function in the NFMA group. Nevertheless, the prevalence of pituitary deficiency postoperatively was still significantly greater in NFMA patients than in the acromegalic group (68% vs. 17%, respectively; P < 0.04). The results suggest that anterior pituitary function is better preserved in GHMA than in NFMA and that this difference is independent of tumor size. The mechanism underlying the lower rate of hypopituitarism in acromegalics with macroadenomas remains to be elucidated.

Activating mutations of the Gs alpha-gene in nonfunctioning pituitary tumors.

The majority of pituitary tumors are of monoclonal origin; however, the molecular basis for their formation is poorly understood. Somatic mutations in the alpha-subunit of the GTP-binding protein, Gs alpha (gsp oncogene) have been found in about one third of GH-secreting tumors. Mutations in another alpha-subunit of a GTP-binding protein, Gi2 alpha (gip mutations) have been described in other endocrine tumors. In this study, we examined 21 nonfunctioning pituitary tumors and 4 macroprolactinomas for gsp mutations and 27 nonfunctioning tumors and 4 macroprolactinomas for gip mutations. Using the polymerase chain reaction and denaturing gradient gel electrophoresis, 2 nonfunctioning pituitary tumors displayed migration abnormalities when the Gs alpha-gene was analyzed. Sequence analysis of these abnormally migrating polymerase chain reaction products revealed two previously known gsp mutations: arginine at codon 201 altered to cysteine, and glutamine at codon 227 changed to leucine. No gip mutations could be demonstrated. These findings emphasize the monoclonal origin of nonfunctioning pituitary tumors and suggest that cAMP may play a role in tumorigenesis of nonfunctioning pituitary tumors.

Organization of layers II-III connections in human visual cortex revealed by in vitro injections of biocytin.

In the search for cortical mechanisms subserving psychological phenomena, a better understanding of human cortical circuitry is crucial. In this report we describe aspects of intrinsic connectivity of supragranular layers in human visual cortex, revealed by extracellular injections of the anterograde tracer biocytin in vitro. Human cortical slices were obtained from visual association cortex in the posterior-medial portion of the dorsal bank of the occipital lobe, removed during neurosurgical tumor ablations. Small iontophoretic injections of biocytin into layers II-III revealed intense Golgi-like staining of axonal projections emanating from the injection sites. Vertically descending axons are grouped in bundles 20 microns in diameter which are spaced 15 microns apart. Some of these axons enter the white matter and send long oblique and horizontal collaterals. The main horizontal spread of the axons could be observed in layers II-III and V. The bulk of projections extends to a distance of 1.5 mm in layers II-III and 1.1 mm in layer V. Few individual axons could be observed at greater distances. In contrast, layer IV is almost devoid of horizontal connections, forming a clear gap between supra- and infragranular layers. Axon collaterals in the infragranular layers project mostly in a descending oblique direction with long horizontal collaterals in lower layer VI.

Epidural haematoma: computerized tomography (CT) parameters in 19 patients.

Between the years 1984 to 1989, 624 urgent brain CT examinations were performed for head-trauma patients in the Tel-Aviv Medical Center. In 19 patients, epidural haematomas were diagnosed. Different radiological parameters were discussed such as homogeneity of the haematoma, midline shift, ventricular collapse, obliteration of the peri-mesencephalic cistern and the presence of additional brain damage.

Spinal epidural compression in chronic lymphocytic leukemia.

Spinal epidural compression is a rare neurologic complication in patients with lymphoma. It occurs mostly in those with intermediate-grade to high-grade malignancy disease. This type of neurologic involvement has not been described in chronic lymphocytic leukemia (CLL). A patient with a long, stable CLL course developed spinal epidural compression and consequently died. The frequency of spinal epidural compression in lymphoma, according to the histologic subtypes and the considerations in making the right choice of therapy are discussed in light of the presented case.

New methods of treatment of severely injured sciatic nerve and spinal cord. An experimental study.

It has been demonstrated that low-energy laser irradiation (LELI) applied simultaneously to the injured sciatic nerve and the corresponding segment of the spinal cord, accelerates the process of regeneration of the injured peripheral nerve. A beneficial influence of LELI was also observed when it was applied to the spinal cord following transection and implantation of a segment of an autologous sciatic nerve, but further studies are necessary to evaluate if real regeneration or only earlier distal cord automatism occurred. Both methods are proposed for treatment of peripheral nerve lesions (PNS) and spinal cord injuries.

Infratentorial epidermoids.

Infratentorial epidermoids are rarely seen in the lifetime of a neurosurgeon. Most published series consist of a dozen or so cases. In a period of 20 years we operated on only 6 such patients. Five are doing excellently, one patient died two and a half months after operation of a fulminating infection. The follow-up is of 20 years, 9 years, and 3 years of the first three patients, while the remaining three were operated during the last year. Such an accelerated pace of epidermoid incidence in our department during the last year may be fortuitous, but may also be an indication that, many patients with vague complaints who had an epidermoid, had been missed in the past. Undoubtedly, the CT scan has greatly facilitated the diagnosis of epidermoid cysts, whether infra- or supratentorial. Diagnosis, however, hinges on suspicion or awareness on clinical grounds of the possibility of an infratentorial epidermoid. The analysis of the clinical presentation in our 6 cases, seems to allow the division of infratentorial epidermoids into those that are posteriorly located, which uniformly manifested at some stage of illness raised intracranial pressure, and the anterior epidermoids in the cerebello-pontine angle characterized by the insidious involvement of cranial nerves. Computerized tomography, in some cases with the adjunct of Metrizamide cisternography, confirms the diagnosis and delineates the spread of the lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulatory effect of He-Ne low dose laser on injured sciatic nerves of rats.

Injury to a mammalian peripheral nerve is accompanied by a restorative process that is manifested after a delay. This process is expressed morphologically by the emergence of new nerve fibers. Restoration of function occurs when the regenerating fibers reconnect with the target organ. Because of the low rate of fiber elongation, the denervated target is partially degenerated by the time that the regenerating fibers approach it. To prevent such an atrophy, one must find a way to prevent the degeneration of the nerve, to speed up regeneration, or to maintain the target during the period of nerve degeneration. In the present work, we examined the potential of treatment with low energy laser radiation for improving regeneration or preventing degeneration of mammalian peripheral nerve after injury. After repeated injury for 20 consecutive days, treatment of the sciatic nerve of the rat with low energy laser (He-Ne, 17 mW) caused a significant increase in the amplitude of the action potential recorded in the corresponding gastrocnemius relative to the action potential of injured but not treated nerves. The action potential of the injured sciatic nerves that were laser-irradiated increased to values close to that of a noninjured nerve. The studies include follow-up for 1 year after the injury. This electrophysiological manifestation of the effect of laser treatment on injured nerves was accompanied by a diminution of the size of the scar tissue from these nerves. Yet to be resolved is whether these two phenomena (i.e., electrophysiological and morphological responses) coincide or whether they relate to each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Delayed epidural hematoma. A review.

Since the CT has become the main diagnostic tool in head trauma, more cases of DEDH have become confirmed and published although some have been classified among other entities and under different criteria. This review tries to describe the characteristics of DEDH based on the cases previously published, as well as on three of our own cases. The entity is mainly radiological i.e. appearance of an epidural hematoma in a CT scan following up a previous one which has not shown this pathology. Although not specific, we have found some common features among the cases published. The patients are usually young people. The cause of many injuries is either a fall injury or involvement of a pedestrian in a road accident. Skull fracture under which the DEDH develops is the rule. DEDH is not found in the usual location of the classic epidural hematoma (the temporal fossa). Some of the patients developed DEDH after an earlier neurosurgical operation for evacuation of another traumatic mass lesion for urgent decompression. Others developed DEDH after medical treatment aimed at restoring normal blood pressure or reducing increased ICP. This main group of patients had other associated lesions, mainly intracranial. The others (including our case no. 1) were considered to have a skull fracture associated only with concussion of the brain, as the clinical picture changed or persistent headache developed, another CT scan was indicated and DEDH was then found. This group constitutes those patients in whom the prognosis is expected to be good or excellent. Keeping in mind the necessity for repeated CT scans in this group (we think the number will increase in the future), other patients will benefit from the awareness of the clinician of the importance of this diagnostic tool. CT scan is efficient, accurate and can be repeated at short intervals. It enables a correct diagnosis to be made in nearly 100% of cases of head trauma. Although this liberal use of CT may increase the number of negative scans, it will also increase the number of DEDH's diagnosable at an earlier stage.

Response of peripheral nerve to He-Ne laser: experimental studies.

Low-energy He-Ne laser irradiation (LELI) was found to affect the electric activity and morphology in both intact and severely injured peripheral nerves in rats. Action potential (AP) in the healthy nerve increased by 33% following a single transcutaneous irradiation. Similar irradiation in crushed nerves caused AP to increase significantly over the AP of nonirradiated crushed nerve. Morphological observations revealed that a laser-irradiated injured nerve had diminished scar tissue as compared to an injured but not an irradiated nerve.

HeNe laser irradiation delivered transcutaneously: its effect on the sciatic nerve of rats.

For our study of the effect of low energy laser irradiation (LELI) on living tissue we used HeNe laser on rats. The exponential absorption was reaffirmed in the living tissues overlying the sciatic nerve. An optimal range of energy between 3.5 and 7 J--associated with energy concentration of 4-10 J/cm2 delivered transcutaneously--was found to cause a significant increase in action potential in the sciatic nerve. The effect lasted for more than 8 months after the irradiation session.

Electrophysiological effect of HeNe laser on normal and injured sciatic nerve in the rat.

The effect of low energy CW HeNe laser irradiation on normal and dissected nerves in the rat was examined. The methods are described. Results are compared to the laser effect on other living tissues. HeNe irradiation was found to increase significantly the action potentials of the nerves. It was found to be a long-lasting effect, keeping an increase in the nerves action potential for more than eight months after irradiation has been stopped. A possible explanation for the way the irradiation acts on the nerve is suggested.

Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin.

Epidermal growth factor (EGF), through interaction with specific cell surface receptors, generates a pleiotropic response that, by a poorly defined mechanism, can induce proliferation of target cells. Subversion of the EGF mitogenic signal through expression of a truncated receptor may be involved in transformation by the avian erythroblastosis virus (AEV) oncogene v-erb-B, suggesting that similar EGF receptor defects may be found in human neoplasias. Overexpression of EGF receptors has been reported on the epidermoid carcinoma cell line A431, in various primary brain tumours and in squamous carcinomas. In A431 cells the receptor gene is amplified. Here we show that 4 of 10 primary brain tumours of glial origin which express levels of EGF receptors that are higher than normal also have amplified EGF receptor genes. Amplified receptor genes were not detected in the other brain tumours examined. Further analysis of EGF receptor defects may show that such altered expression and amplification is a particular feature of certain human tumours.

Amplification and overexpression of the EGF receptor gene in primary human glioblastomas.

The expression of epidermal growth factor (EGF) receptor in brain tumours of glial origin was studied at the protein, mRNA and genomic levels. Four out of 10 glioblastomas that overexpress EGF receptor also have gene amplification. The amplified genes appear to be rearranged, generating an aberrant mRNA in at least one of these tumours. Such receptor defects may be relevant to tumorigenesis of human glioblastomas.

Characterization of activities and forms of cholinesterases in human primary brain tumors.

The activities and molecular forms of cholinesterases were studied in a collection of primary brain tumors consisting of primarily gliomas and meningiomas, together with samples of forebrain taken postmortem from patients suffering from diseases unrelated to the nervous system. Both types of tumors, as well as normal forebrain, contained substantial amounts of cholinesterase activity and some gliomas contained exceptionally high levels. In both normal forebrain and meningiomas, acetylcholinesterase (acetylcholine hydrolase; EC 3.1.1.7) accounted for almost all the cholinesterase activity, but in almost all gliomas elevated pseudocholinesterase (acylcholine acylhydrolase; EC 3.1.1.8) could be detected. The cholinesterase activity of both normal forebrain and gliomas migrated on sucrose gradients as a major component of 10-11 S together with a minor component of 4-5 S. In meningiomas a light (4.5 S) form was the principal component.