Reduced-dose radiosurgery for vestibular schwannomas.

OBJECTIVE: To evaluate tumor control and complications associated with low-dose radiosurgery for vestibular schwannomas. METHODS: Between December 1993 and January 2000, 47 patients with vestibular schwannomas were treated at our center with gamma knife radiosurgery. The marginal tumor doses ranged from 7.5 to 14.0 Gy (median, 12.0 Gy) for patients treated after microsurgery and from 10.0 to 15.0 Gy (median, 12.0 Gy) for patients in whom radiosurgery was the primary treatment. The median maximum tumor diameter was 18 mm (range, 3-50 mm). Evaluation included audiometry, neurological examination, and serial imaging tests. A survey was conducted at the time of analysis. RESULTS: Follow-up data were available for 45 patients and ranged from 1 to 7 years (median, 3.6 yr). In 43 patients (96%), tumor control (no radiographic progression or surgical resection) was observed. All 33 previously untreated patients had tumor control. Transient facial weakness, experienced in two patients (4%), had resolved completely within 6 months. No patient developed trigeminal neuropathy. Hearing was diminished from baseline in 12% of patients with useful hearing (Gardner-Robertson Class III). However, all patients with pretreatment hearing Gardner-Robertson Class I or II maintained testable hearing (Class I to III) at the most recent examination. CONCLUSION: Low-dose radiosurgery in this series provided comparable local control and decreased incidences of complications in relation to other reports. Additional follow-up will allow more definitive conclusions to be reached regarding the ultimate rates of tumor control and hearing preservation. Nevertheless, the current dose used for vestibular schwannomas at the University of Maryland Medical Center is 12.0 Gy to the tumor periphery.

Neuronal nicotinic receptors in synaptic functions in humans and rats: physiological and clinical relevance.

The present report describes the participation of nicotinic receptors (nAChRs) in controlling the excitability of local neuronal circuitries in the rat hippocampus and in the human cerebral cortex. The patch-clamp technique was used to record responses triggered by the non-selective agonist ACh and the alpha7-nAChR-selective agonist choline in interneurons of human cerebral cortical and rat hippocampal slices. Evidence is provided that functional alpha7- and alpha4beta2-like nAChRs are present on somatodendritic and/or preterminal/terminal regions of interneurons in the CA1 field of the rat hippocampus and in the human cerebral cortex and that activation of the different nAChR subtypes present in the preterminal/terminal areas of the interneurons triggers the tetrodotoxin-sensitive release of GABA. Modulation by nAChRs of GABAergic transmission, which can result either in inhibition or disinhibition of pyramidal neurons, depends both on the receptor subtype present in the interneurons and on the agonist acting upon these receptors. Not only do alpha7 nAChRs desensitize faster than alpha4beta2 nAChRs, but also alpha7 nAChR desensitization induced by ACh lasts longer than that induced by choline. These mechanisms, which appear to be retained across species, might explain the involvement of nAChRs in cognitive functions and in such neurological disorders as Alzheimer's disease and schizophrenia.

Nicotinic receptor activation in human cerebral cortical interneurons: a mechanism for inhibition and disinhibition of neuronal networks.

Cholinergic control of the activity of human cerebral cortical circuits has long been thought to be accounted for by the interaction of acetylcholine (ACh) with muscarinic receptors. Here we report the discovery of functional nicotinic receptors (nAChRs) in interneurons of the human cerebral cortex and discuss the physiological and clinical implications of these findings. The whole-cell mode of the patch-clamp technique was used to record responses triggered by U-tube application of the nonselective agonist ACh and of the alpha7-nAChR-selective agonist choline to interneurons visualized by means of infrared-assisted videomicroscopy in slices of the human cerebral cortex. Choline induced rapidly desensitizing whole-cell currents that, being sensitive to blockade by methyllycaconitine (MLA; 50 nM), were most likely subserved by an alpha7-like nAChR. In contrast, ACh evoked slowly decaying whole-cell currents that, being sensitive to blockade by dihydro-beta-erythroidine (DHbetaE; 10 microM), were most likely subserved by an alpha4beta2-like nAChR. Application of ACh (but not choline) to the slices also triggered GABAergic postsynaptic currents (PSCs). Evidence is provided that ACh-evoked PSCs are the result of activation of alpha4beta2-like nAChRs present in preterminal axon segments and/or in presynaptic terminals of interneurons. Thus, nAChRs can relay inhibitory and/or disinhibitory signals to pyramidal neurons and thereby modulate the activity of neuronal circuits in the human cerebral cortex. These mechanisms, which appear to be retained across species, can account for the involvement of nAChRs in cognitive functions and in certain neuropathological conditions.

Choline and selective antagonists identify two subtypes of nicotinic acetylcholine receptors that modulate GABA release from CA1 interneurons in rat hippocampal slices.

Neuronal nicotinic receptors (nAChR) are known to control transmitter release in the CNS. Thus, this study was aimed at exploring the diversity and localization of nAChRs present in CA1 interneurons in rat hippocampal slices. The use of a U-tube as the agonist delivery system was critical for the reliable detection of nicotinic responses induced by brief exposure of the neurons to ACh or to the alpha7 nAChR-selective agonist choline. The present study demonstrated that CA1 interneurons, in addition to expressing functional alpha7 nAChRs, also express functional alpha4beta2-like nAChRs and that activation of both receptors facilitates an action potential-dependent release of GABA. Depending on the experimental condition, one of the following nicotinic responses was recorded from the interneurons by means of the patch-clamp technique: a nicotinic whole-cell current, depolarization accompanied by action potentials, or GABA-mediated postsynaptic currents (PSCs). Responses mediated by alpha7 nAChRs were short-lasting, whereas those mediated by alpha4beta2 nAChRs were long-lasting. Thus, phasic or tonic inhibition of CA1 interneurons may be achieved by selective activation of alpha7 or alpha4beta2 nAChRs, respectively. It can also be suggested that synaptic levels of choline generated by hydrolysis of ACh in vivo may be sufficient to control the activity of the alpha7 nAChRs. The finding that methyllycaconitine and dihydro-beta-erythroidine (antagonists of alpha7 and alpha4beta2 nAChRs, respectively) increased the frequency and amplitude of GABAergic PSCs suggests that there is an intrinsic cholinergic activity that sustains a basal level of nAChR activity in these interneurons.

Time-frequency analysis using the matching pursuit algorithm applied to seizures originating from the mesial temporal lobe.

OBJECTIVES: The ability to analyze patterns of recorded seizure activity is important in the localization and classification of seizures. Ictal evolution is typically a dynamic process with signals composed of multiple frequencies; this can limit or complicate methods of analysis. The recently-developed matching pursuit algorithm permits continuous time-frequency analyses, making it particularly appealing for application to these signals. The studies here represent the initial applications of this method to intracranial ictal recordings. METHODS: Mesial temporal onset partial seizures were recorded from 9 patients. The data were analyzed by the matching pursuit algorithm were continuous digitized single channel recordings from the depth electrode contact nearest the region of seizure onset. Tine frequency energy distributions were plotted for each seizure and correlated with the intracranial EEG recordings. RESULTS: Periods of seizure initiation, transitional rhythmic bursting activity, organized rhythmic bursting activity and intermittent bursting activity were identified. During periods of organized rhythmic bursting activity, all mesial temporal onset seizures analyzed had a maximum predominant frequency of 5.3-8.4 Hz with a monotonic decline in frequency over a period of less than 60 s. The matching pursuit method allowed for time-frequency decomposition of entire seizures. CONCLUSIONS: The matching pursuit method is a valuable tool for time-frequency analyses of dynamic seizure activity. It is well suited for application to the non-stationary activity that typically characterizes seizure evolution. Time-frequency patterns of seizures originating from different brain regions can be compared using the matching pursuit method.

Assessment of training progress and examinations.

Board certification and accreditation of training programs began as measures of quality in the United States. Both functions were done initially by the American Board of Neurological Surgery (ABNS). In 1954, certification of trainees and accreditation of programs became separate functions in order to eliminate potential conflicts of interest. Currently, the ABNS certifies trainees who have completed neurological surgery training in an accredited program whose curriculum includes operative and nonoperative experience, have the endorsement of the training program director, and have passed the written in-training examinations and a final oral examination. Accreditation of training programs is a separate function administered by the Residency Review Committee (RRC) of the Accreditation Council for Graduate Medical Education. Individual programs are reviewed on a periodic basis for quality of the curriculum, facilities, faculty, and patient volume. The ABNS and the RRC are separate groups, both comprised of neurosurgeons with a strong commitment to the educational process.

Cell and molecular biology for neurosurgeons (or everything you wanted to know about molecular biology but were afraid to download).

We are fortunate to be physicians at a time when the molecular pathogenesis of disease is being unraveled. Beginning with the discovery of the structure of DNA to the Human Genome Project, molecular biology over the past 45 years has revolutionized medicine. Neurosurgery has a strong scientific tradition, but to remain active participants in this new era of medicine, we must understand the science of pathology at the molecular level, applying our unique perspective to its advancement. We will review most of the current techniques used today by cell and molecular biologists. Interwoven with these descriptions will be a brief discussion of pertinent molecular and cell biology concepts, a full review being beyond the scope of this article.

Ventriculostomy infections: the effect of monitoring duration and catheter exchange in 584 patients.

The investigators undertook a retrospective analysis of ventriculostomy infections to evaluate their relationship to monitoring duration and prophylactic catheter exchange. In 1984, the results of an epidemiological study of ventriculostomy-related infection were published. One of the conclusions of the paper was that the incidence of ventriculostomy-related infections rose after 5 days of monitoring. This led to the recommendation that catheters be prophylactically changed at 5-day intervals if prolonged monitoring was required. A recent randomized prospective study on central venous catheters showed no reduction in infection with prophylactic catheter exchanges. This has led the authors to reexamine their experience with ventriculostomy infections. Data on 584 severely head injured patients with ventriculostomies were prospectively collected in two data banks, The Traumatic Coma Data Bank and The Medical College of Virginia Neurocore Data Bank. These data were retrospectively analyzed for factors associated with ventriculostomy related infections. It was found that there is a relationship of ventriculitis to monitoring duration but it is not simple or linear. There is a rising risk of infection over the first 10 days, but infection then becomes very unlikely despite a population that continues to be at risk. Patients in whom catheters were replaced prior to 5 days did not have a lower infection rate than those whose catheters were exchanged at more than 5-day intervals. Based on these data, it is recommended that ventriculostomy catheters for intracranial pressure monitoring be removed as quickly as possible, and in circumstances in which prolonged monitoring is required, there appears to be no benefit from catheter exchange.

NGF-producing transfected 3T3 cells: behavioral and histological assessment of transplants in nigral lesioned rats.

The rodent fibroblast clonal cell line, 3T3, was retrovirally transfected with the rat nerve growth factor (NGF) gene and selected for NGF synthesis. This study tested the hypothesis that transplanted 3T3 cells, transfected to secrete nerve growth factor (3T3NGF+), change motor behavioral indices created by striatal denervation in a dose-dependent fashion. 3T3NGF+ cells were transplanted into the lateral ventricle of rats following ipsilateral lesions of the substantia nigra pars compacta by stereotaxic injections of 6-hydroxydopamine (10 micrograms), an established lesion model. Control groups included vehicle injections and transplanted untransfected cells. The extent of the lesions was measured by determining rotational behavior before and two weeks after transplantation. Immediately prior to transplantation, cells were incubated with the fluorescent dye marker, Dil. To assess cell viability, whole brains were cryosectioned and examined for Dil-labeled 3T3 cells using fluorescent microscopy. The number of Dil-labeled profiles in five animals per group were counted in at least five noncontiguous sections per animal. From these data a statistically derived estimate of viable, transplanted 3T3 cells was obtained. The number of surviving transplanted cells correlated with the behavioral changes measured. The 3T3NGF+ transplants reduced rotational behavior, while control 3T3 transplants exacerbated rotational behavior. Thus, while NGF delivery was found to be beneficial, it was apparent that naive 3T3 had detrimental effects. These results underscore the importance of making dose-response measurements when attempting transplant-based modifications of CNS behavior.

Reversible amnesia associated with a left temporal hematoma in a case of right temporal complex partial seizures.

We report the case of a 44-year-old woman with complex partial seizures (CPS) of right frontotemporal origin who developed generalized amnesia after undergoing intracranial electrode implantation complicated by left hippocampal hemorrhage. Serial memory testing disclosed recovery from the amnesic disorder, while repeated magnetic resonance imaging (MRI) showed resolution of her left hippocampal hemorrhage in a 2-month period. A second intracarotid amytal procedure confirmed the capability of her left temporal region to support memory. Consequently, a right orbitofrontotemporal lobectomy was performed without complication.

Neurobehavioural consequences of closed head injury in older adults.

This study examined the neurobehavioural effects of closed head injury (CHI) in adults aged 50 years and older. Twenty two mild to moderate CHI patients who were within seven months of the injury were administered measures of language, memory, attention, and executive functioning. Compared with demographically similar normal controls, the patients exhibited significantly poorer functioning on the cognitive domains. Naming and word fluency under timed conditions, verbal and visual memory, and the ability to infer similarities were especially vulnerable. These initial findings indicate that CHI in older adults produces considerable cognitive deficits in the early stages of recovery. Future research should characterise long term outcome and the potential links between head injury and the development of progressive dementia.

Dissociation between delayed alternation and memory after pediatric head injury: relationship to MRI findings.

This study investigated the usefulness of a delayed alternation task in characterizing the cognitive sequelae of closed head injury in children and adolescents. Verbal learning and memory (California Verbal Learning Test) were also studied for comparison. Sixty-two closed head injury patients (mean age, 9.6 years), who were studied after an average postinjury interval of 20 months, were divided according to both their lowest postresuscitation Glasgow Coma Scale score (3 to 8 versus 9 to 15) and age range (5 to 7 years versus 8 to 16 years) at the time of testing. Magnetic resonance imaging was performed to evaluate the relationship of focal brain lesions to cognitive and memory performance. Fifty-six neurologically normal children (mean age, 9.9 years) were tested on the same measures. The results disclosed no relationship between delayed alternation performance and severity of injury. In contrast, verbal memory was impaired in the severely-injured patients, relative to both controls and less severely-injured patients. Frontal lobe (but not extrafrontal) lesion size incremented the Glasgow Coma Scale score in predicting verbal memory, but there was no relationship between focal brain lesions and delayed alternation performance. In contrast to the tendency for more efficient delayed alternation performance in the 5- to 7-year-old subjects than in the 8- to 16-year-old subjects, verbal memory significantly improved with age in the closed head injury and control groups. Notwithstanding our essentially negative findings for delayed alternation, it is possible that this task may be useful for assessing frontal lobe injury in younger children or infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Cognition in relation to magnetic resonance imaging in head-injured children and adolescents.

To investigate the relationship between cognitive sequelae and magnetic resonance imaging (MRI) findings following closed head injury of varying severity in the pediatric age range, 76 head-injured children and adolescents were studied at least 3 months after trauma and compared with 57 normal controls. Problem solving, planning, verbal and design fluency, memory, and response modulation were assessed. Significant effects of injury were obtained on all of the cognitive measures. Cognitive impairment was more consistently present on the various outcome measures in children who were 6 to 10 years old at the time of the study than in the older children and adolescents. Magnetic resonance imaging disclosed areas of abnormal signal in the frontal lobes of 42 patients, whereas focal lesions restricted to the extrafrontal region were found in 15 children. Regression analyses disclosed that taking into account the size of frontal lobe lesion enhanced the relationship between cognitive performance and the severity of injury.

Effects of transcallosal surgery on interhemispheric transfer of information.

The effects of transcallosal surgery on interhemispheric transfer of information were investigated in five patients who underwent partial section of the corpus callosum for evacuation of a brain tumor. In comparison with normal controls, postoperative findings indicated subtle motor and/or sensory manifestations of hemispheric disconnection which tended to resolve overtime. However, in no case were the disconnection effects disabling in the performance of daily activities.

Relationship between Glasgow Outcome Scale and neuropsychological measures after brain injury.

The present study was conducted to further our understanding of the relationship between performance on neuropsychological tests and functional status after head injury and to provide information on the relative usefulness of neuropsychological tests as outcome measures in clinical trials of brain injury. We sought to select the fewest number of 19 neuropsychological tests administered to 110 patients that, in combination, were most closely related to outcome (as measured by the Glasgow Outcome Scale (GOS) and to the remaining neuropsychological measures. The relationship of memory and intellectual deficits to functional status was also considered. To address these questions, we analyzed 19 neuropsychological measures and GOS scores of 110 severely brain injured patients from the Traumatic Coma Data Bank. Of 19 neuropsychological measures compared with GOS at 3 and 6 months, four tests (Controlled Oral Word Association, Grooved Pegboard, Trailmaking Part B, and Rey-Osterrieth Complex Figure Delayed Recall) provided the closest relationship to GOS and to the remaining 15 tests. Similar analyses were performed on 30 moderately injured patients to test the generality of our findings across different levels of patient severity. The same four tests were found to be highly predictive of GOS. Grooved Pegboard, a test of fine motor coordination, accounted for 80% of the variation in GOS. Fifteen percent of 116 patients with severe brain injury could not complete a neuropsychological battery and 39% were excluded because of previous brain injury or known substance abuse.

Visual evoked magnetic fields reveal activity in the superior temporal sulcus.

Evoked magnetic fields to randomized infrequent omissions of visual stimuli resulted in a magnetic field pattern over the right hemisphere consistent with a dipolar source and led to localization of this source within the superior temporal sulcus. Previous investigations using implanted microelectrodes, ablation/lesion procedures in monkeys and observations of behavioral anomalies following injury in humans have already indicated the importance of the inferior portions of the temporal lobe in visual processing. However, until now, no method was available to study noninvasively the role of temporal cortex during visual processing.

Magnetoencephalography reveals two distinct sources associated with late positive evoked potentials during visual oddball task.

The present investigation was undertaken in order to utilize magnetoencephalography to locate generator sources, modeled as equivalent current point dipoles, that account for the well-established late positive electrical potentials commonly measured along the midline (Cz, Pz, Fz, and Oz) in response to rare or task-relevant stimuli and their simultaneously recorded magnetic field components. Two simultaneous but spatially distinct sources were present in all six subjects. One source in which the magnetic flux exited and reentered the brain over the right hemisphere was localized in deep structures under the temporal cortex in the vicinity of the right hippocampal formation. The other occurred in the vicinity of the primary visual cortex in the occipital area with magnetic flux entering and exiting over the posterior aspects of the subjects' heads. These data correspond to depth and surface electrode studies that have demonstrated multiple generator sources.

Predictors of outcome following severe head trauma: follow-up data from the Traumatic Coma Data Bank.

Outcome as a function of employment status or return to school was evaluated in severely head-injured patients. A priori we selected the most salient demographic, physiological, neuropsychological and psychosocial outcome predictors with the aim of identifying which of there variables captured at baseline or 6 months would best predict employability at 6 or 12 months. Based on the patients evaluated at 6 months, 18% of former workers had returned to gainful employment and 62% of former students had returned to school. For those not back to work or school at 6 months, 31% of the former workers and 66% of the former students had returned by 12 months. Age, length of coma, speed for both attending and motor movements, spatial integration, and intact vocabulary were all significantly related to returning to work or school. The three most potent predictors for returning to work or school were intactness of the patient's verbal intellectual power, speed of information processing and age.