Neurofibromatosis 2 and malignant mesothelioma.

Mutations of the neurofibromatosis 2 (NF2) tumor suppressor gene cause the inherited disorder NF2 and are also common in malignant mesothelioma, which is not a characteristic feature of NF2. The authors report an asbestos-exposed person with NF2 and malignant mesothelioma. Immunohistochemical analysis of the mesothelioma confirmed loss of expression of the NF2 protein, and comparative genomic hybridization revealed losses of chromosomes 14, 15, and 22, and gain of 7. The authors propose that a person with a constitutional mutation of an NF2 allele is more susceptible to mesothelioma.

Microsurgical treatment of symptomatic sacral Tarlov cysts.

OBJECTIVE: Providing relief of symptomatic radiculopathy resulting from sacral perineural cysts has proven difficult. Our goal was to improve the treatment of these cysts with microsurgical cyst fenestration and imbrication, while minimizing functional damage to neural tissues. METHODS: We retrospectively reviewed the records for eight adult patients with large (2-3-cm) sacral perineural cysts who were treated at the University of California, San Francisco, between October 1992 and April 1999. All patients presented with radicular pain that was refractory to medical treatment. Three patients also reported urinary incontinence. We performed sacral laminectomies with microsurgical cyst fenestration and cyst imbrication for all patients, using intraoperative electromyography to minimize damage to the sacral nerve roots. For seven patients, we reinforced the closures with epidural fat or muscle grafts and fibrin glue application. For five patients with cysts that communicated with the subarachnoid space in computed tomographic myelograms, we placed lumbar drains for cerebrospinal fluid diversion for several days postoperatively. We assessed outcomes, using telephone questionnaires and periodic postoperative physical examinations, 3 to 73 months after surgery. RESULTS: After surgery, radicular pain improved markedly for four patients and moderately for three patients; one patient with initial improvement experienced pain recurrence 9 months later. Bladder control improved markedly for two of the three patients with bladder dysfunction. There were no cerebrospinal fluid leaks and no new postoperative neurological deficits. CONCLUSION: Microsurgical cyst fenestration and imbrication are effective treatments for long-term relief of refractory painful radiculopathy and urinary incontinence associated with large sacral perineural cysts.

Lesions of the internal auditory canal and cerebellopontine angle in an only hearing ear: is surgery ever advisable?

OBJECTIVE: To define the indications for surgery in lesions of the internal auditory canal (IAC) and cerebellopontine angle (CPA) in an only hearing ear. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Seven patients with lesions of the IAC and CPA who were deaf on the side opposite the lesion. Five patients had vestibular schwannoma (VS), and one each had meningioma and progressive osseous stenosis of the IAC, respectively. The opposite ear was deaf from three different causes: VS (neurofibromatosis type 2 [NF2]), sudden sensorineural hearing loss, idiopathic IAC stenosis. INTERVENTION(S): Middle fossa removal of VS in five, retrosigmoid resection of meningioma in one, and middle fossa IAC osseous decompression in one. MAIN OUTCOME MEASURE: Hearing as measured on pure-tone and speech audiometry. RESULTS: Preoperative hearing was class A in four patients, class B in two, and class C in one. Postoperative hearing was class A in three patients, class B in one, class C in two, and class D in one. CONCLUSIONS: Although the vast majority of neurotologic lesions in an only hearing ear are best managed nonoperatively, in highly selected cases surgical intervention is warranted. Surgical intervention should be considered when one or more of the following circumstances is present: (1) predicted natural history of the disease is relatively rapid loss of the remaining hearing, (2) substantial brainstem compression has evolved (e.g., large acoustic neuroma), and/or (3) operative intervention may result in improvement of hearing or carries relatively low risk of hearing loss (e.g., CPA meningioma).

Cerebral oxygenation during hemorrhagic shock: perils of hyperventilation and the therapeutic potential of hypoventilation.

OBJECTIVES: Prophylactic hyperventilation of patients with head injuries worsens outcome, presumably by exacerbating tissue hypoxia. Oxygen tension in brain tissue (PbrO2) provides a direct measurement of cerebral metabolic substrate delivery and varies with changing end-tidal carbon dioxide tension (ETCO2) and mean arterial pressure. However, the effects of hyperventilation and hypoventilation on PbrO2 during hemorrhagic shock are not known. The aim of this study was to examine the effects of alteration in ventilation on PbrO2 in hemorrhaged swine. METHODS: Clark-type polarographic probes were inserted into the brain tissue of seven swine to measure PbrO2 directly. To examine the effects of alterations in ventilation on hemorrhage-induced hypotension, swine were hemorrhaged to 50% estimated blood volume and PbrO2 was monitored during hyperventilation (RR = 30) and hypoventilation (RR = 4). RESULTS: After the 50% hemorrhage, PbrO2 declined rapidly from 39.8 +/- 4.6 mm Hg to 11.4 +/- 2.2 mm Hg. Hyperventilation resulted in a further 56% mean decrease in PbrO2. Hypoventilation produced a 166% mean increase in PbrO2. These changes were significant (p = 0.001) for absolute and percentage differences from baseline. CONCLUSION: During hemorrhage, alterations in ventilation significantly changed PbrO2: hyperventilation increased brain-tissue hypoxia whereas hypoventilation alleviated it. This finding suggests that hyperventilation has deleterious effects on brain oxygenation in patients with hemorrhagic shock and those with head trauma. Conversely, hypoventilation with resultant hypercapnia may actually help resolve hemorrhagic shock-induced cerebral hypoxia.

Is the entire fundus of the internal auditory canal visible during the middle fossa approach for acoustic neuroma?

HYPOTHESIS: To determine the degree to which the fundus of the internal auditory canal (IAC) can be visualized during the middle fossa approach (MFA). BACKGROUND: Conventional wisdom states that the MFA provides excellent access to the IAC from the porus acusticus to the fundus. On the basis of observations derived from a substantial surgical experience, it became obvious that a variable fraction of the fundus lies obscure from the surgeon's line of sight during the MFA because of (1) the overhand of the transverse crest and/or (2) the immobility of the facial nerve at its entry into the fallopian canal. METHODS: Intraoperative measurements were performed in ten cases to determine the typical angle of view to the fundus of the IAC in the MFA. This angle of view was projected onto coronal computed tomography scans of 40 temporal bones. Measurements of the IAC were made to determine the amount of fundus that could not be directly visualized during a MF exposure. RESULTS: On the basis of a surgical line of sight, the fraction of the inferior compartment of the canal that could not be directly visualized because of overhand of the transverse crest ranged from 14% to 34% (median 25%). CONCLUSIONS: Complete resection of IAC tumors involving the fundus via the MFA requires some degree of blind dissection. Specialized tools and techniques are required to minimize the risk of neural injury during this indirect dissection. Inspection of the fundus with either mirror or endoscope is often necessary to exclude the possibility of retained tumor fragments.

Extradural temporal lobe retraction in the middle fossa approach to the internal auditory canal: biomechanical analysis.

HYPOTHESIS: The middle fossa (MF) approach is undergoing a marked resurgence in vestibular schwannoma surgery as a hearing conservation technique. It is widely recognized that the extradural temporal lobe retractors used in this procedure, despite their cleverness of design, could be improved. METHODS: To identify the characteristics of an ideal MF retractor, a systematic analysis of the safety and functionality of four commonly used retractors (House-Urban, Fisch, Garcia-Ibanez, and UCSF) in a human anatomical model was conducted. Intensity of temporal lobe compression, width of exposure, angle of visualization, obstruction to instrument access, ergonomic convenience of use, and adaptability to other subtemporal procedures (e.g. lesions of Meckel's cave and cavernous sinus) were quantified. RESULTS: Because the intracranial portions of the retractors are similar, the force transmitted to the brain differed little among the four retractors. Numerous differences were noted in the ergonomics of use and versatility of the various designs. CONCLUSIONS: The optimal MF retractor would incorporate the best features of each of the existing systems: the integral suction of the Garcia-Ibanez, the bone contour-following design of the Fisch retractor base, the unobtrusiveness and adaptability of the UCSF, and the three-plane adjustability of the vintage House-Urban. Evolution of an "ideal" MF retractor requires further technical refinements and the development of an experimental model of extradural brain retraction to assess the optimal strategy for obtaining exposure while minimizing the risk for temporal lobe injury.

Brain tissue oxygenation during hemorrhagic shock, resuscitation, and alterations in ventilation.

OBJECTIVES: Recently developed polarographic microelectrodes permit continuous, reliable monitoring of oxygen tension in brain tissue (PbrO2). The aim of this study was to investigate the feasibility and utility of directly monitoring PbrO2 in cerebral tissue during changes in oxygenation or ventilation and during hemorrhagic shock and resuscitation. We also sought to develop a model in which treatment protocols could be evaluated using PbrO2 as an end point. METHODS: Licox Clark-type polarographic probes were inserted in the brain tissue of 16 swine to monitor PbrO2. In eight swine, changes in PbrO2 were observed over a range of fractional concentrations of inspired O2 (FiO2) as well as during periods of hyperventilation and hypoventilation. In eight other swine, PbrO2 was monitored during a graded hemorrhage of up to 70% estimated blood volume and during the resuscitation period. RESULTS: When FiO2 was elevated to 100%, PbrO2 increased from a baseline of 15+/-2 mm Hg to 36+/-11 mm Hg. Hyperventilation while breathing 100% oxygen resulted in a 40% decrease in PbrO2 (p < 0.05), whereas hypoventilation increased PbrO2 to 88 mm Hg (p < 0.01). A graded hemorrhage to 50% estimated blood volume significantly reduced PbrO2, mean arterial pressure, and intracranial pressure (p < 0.01). Continued hemorrhage to 70% estimated blood volume resulted in a PbrO2 of 2.9+/-1.5 mm Hg. After resuscitation, PbrO2 was significantly elevated, reaching 65+/-13 mm Hg (p < 0.01), whereas mean arterial pressure and cerebral perfusion pressure simply returned to baseline. CONCLUSION: Directly measured PbrO2 was highly responsive to changes in FiO2, ventilatory rate, and blood volume in this experimental model. In particular, hypoventilation significantly increased PbrO2, whereas hyperventilation had the opposite effect. The postresuscitation increase in PbrO2 may reflect changes in both O2 delivery and O2 metabolism. These experiments set the stage for future investigations of a variety of resuscitation protocols in both normal and injured brain.

Primary end points in phase III clinical trials of severe head trauma: DRS versus GOS. The American Brain Injury Consortium Study Group.

The most commonly used primary end point in phase III clinical trials of severe head trauma is the Glasgow Outcome Scale (GOS), usually dichotomized to favorable (good) and unfavorable (poor) outcomes. The alternative endpoints include the Disability Rating Scale (DRS) with a 31-point scale. The purpose of this study was to compare DRS and GOS using the data collected from two completed clinical trials organized by the American Brain Injury Consortium and two pharmaceutical companies. The two outcome scales were examined and compared in terms of the correlation between the two scales, sensitivity, and p values between the differences between two arms of the trials. There was no indication that the DRS was more sensitive or advantageous relative to the dichotomized or four-category GOS. In addition, the highly significant correlation between the two outcome scales (r = 0.95; p < 0.0001) could not justify the DRS as an end point. The other problems with the DRS include the difficulty of determining the clinically meaningful difference in designing trials. The study suggested that the GOS is a better primary end point than DRS.

Hearing preservation in patients undergoing vestibular schwannoma surgery: comparison of middle fossa and retrosigmoid approaches.

OBJECT: The goal of this retrospective study was to evaluate hearing preservation after surgery for vestibular schwannoma in which the middle fossa (MF) or retrosigmoid (RS) approaches were used. Hearing preservation in vestibular schwannoma surgery can be achieved by using either the MR or RS approach. Comparative outcome data between these approaches are lacking, and, as a result, selection has generally been determined by the surgeon's preference. METHODS: The authors have compared removal of small vestibular schwannomas via MF and RS approaches with regard to hearing preservation and facial nerve function. The study group was composed of consecutively treated patients with vestibular schwannoma, 48 of whom underwent operation via an MF approach and 50 of whom underwent the same number of RS operations. Tumors were divided into size-matched groups. Hearing results were recorded according to the American Academy of Otolaryngology-Head and Neck Surgery criteria, and facial nerve outcome was recorded as the House-Brackmann grade. Overall, 26 (52%) of the patients treated via the MF approach achieved a Class B or better hearing result compared with seven (14%) of the RS group. Some hearing was preserved in 32 (64%) of the patients in the MF group and in 17 (34%) of the RS group. The results obtained by using the MF approach were superior for intracanalicular tumors (p=0.009, t-test), and for tumors with a cerebellopontine angle (CPA) component measuring 0.1 to 1 cm (p=0.006, t-test). For tumors in the CPA that were 1.1 to 2 cm in size, our data were inconclusive because of the small sample size. Facial weakness was seen more frequently after MF surgery in the early postoperative period, but results were equal at 1 year. CONCLUSIONS: The results of this study have demonstrated a more favorable hearing outcome for patients with intracanalicular tumors and tumors extending up to 1 cm into the CPA that were removed via the MF when compared with the RS approach.

Acoustic neuromas presenting with normal or symmetrical hearing: factors associated with diagnosis and outcome.

OBJECTIVE: To evaluate the clinical features leading to diagnosis in patients with acoustic neuroma (AN) who present with normal or symmetrical hearing. Underlying tumor characteristics are also studied to identify a possible explanation for this unique presentation in the AN population. STUDY DESIGN: Retrospective case review comprising patients who were identified as having AN that presented with normal audiometry. SETTING: A tertiary referral center. PATIENTS: Patients with AN who met the criteria for normal were included in the report. For this study, abnormal audiometry is defined as an interaural difference of > or =15 dB at a single frequency or > or =10 dB at two or more frequencies, and an interaural speech reception threshold difference of > or =20 dB, or a speech discrimination score of > or =20%. MAIN OUTCOME MEASURES: Presenting symptoms and signs, clinical features that led to the diagnosis of AN, auditory brain stem response results, tumor location, size and relationship to temporal bone landmarks, surgical intervention, surgical outcome, and results of hearing preservation attempts were tabulated for each patient. RESULTS: A total of 29 patients (5%) were identified who had normal or symmetrical pure-tone audiograms between 500 and 4,000 Hz. The average difference in speech reception threshold between tumor and nontumor ear was 3.2 dB, and the average difference in speech detection score was 2.6%. The most common presenting symptoms that led to the diagnosis of the AN were dysequilibrium/vertigo (12 cases), cranial nerve V and VII abnormalities (11 cases), routine screening for families with neurofibromatosis type 2 (5 cases), asymmetrical tinnitus (4 cases), headaches (4 cases), unilateral subjective hearing difficulty (4 cases), and incidental finding during evaluation for another problem (4 cases). The average tumor size was 19 mm, with five cases presenting with tumors of size > or =30 mm. Nineteen patients underwent a hearing preservation procedure (middle fossa or retrosigmoid), 11 of whom had useful hearing postoperatively. CONCLUSIONS: Despite normal audiometry, patients presenting with imbalance or vertigo, Vth or VIIth cranial nerve deficits, or unilateral hearing complaints may warrant further evaluation to rule out the possibility of AN or other retrocochlear lesion. To seek an explanation for this phenomenon, the incidence of various tumor characteristics (e.g., depth of penetration into the internal auditory canal and degree of porous erosion) is discussed and compared with the entire AN population.

Comparison of response amplitude versus stimulation threshold in predicting early postoperative facial nerve function after acoustic neuroma resection.

OBJECTIVE: This study aimed to better predict the early postoperative facial nerve (FN) function after acoustic neuroma (AN) resection. STUDY DESIGN: This study was a prospective series. SETTING: The surgery was conducted in a tertiary referral center. PATIENTS: A total of 44 patients undergoing AN resection with cranial nerve monitoring were observed for at least 1 year after surgery. MAIN OUTCOME MEASURES: The predictive value of amplitude of the FN stimulus response on the early postoperative FN function was measured. RESULTS: Cranial nerve monitoring in AN surgery was used to obtain the stimulation threshold and facial electromyograph response amplitudes to FN stimulation proximal and distal to the tumor at 0.2 V above threshold. Thirty-eight of forty-four patients studied had a low postresection threshold (< or = 0.1 V). Of these (10), 26% sustained a postoperative FN dysfunction of House-Brackmann (HB) grades 3-6. In an effort to improve the predictive value from cranial nerve monitoring, the response amplitude to suprathreshold stimulation was compared with the threshold and FN function. Eighty-nine percent of patients with an amplitude of > or =200 microV had a grade 1-2 early postoperative FN function, whereas only 41% of patients with < 200 microV had a grade 1-2 early postoperative FN function (p = 0.00035). Eighty-eight percent of patients with both a low threshold and high amplitude had a grade 1-2 early postoperative FN function, whereas the remaining 12% of patients had a grade 3-6 FN function (p = 0.0032). The false-positive rate of threshold alone in predicting a grade 1-2 FN function was 26% compared to 12% for low threshold and high amplitude combined. CONCLUSIONS: The use of FN threshold and amplitude together is superior to threshold alone as a predictor of early postoperative FN function.

Outcome after severe head injury: an analysis of prediction based upon comparison of neural network versus logistic regression analysis.

More reliable prediction of outcome would be helpful for clinicians who treat severely head-injured patients. To determine if neural network modeling would improve outcome prediction compared with standard logistic regression analysis and to determine if data available 24 h after severe head injury allows better prediction than data obtained within 6 h, we tested the ability of both techniques at these two times to predict outcome (dead versus alive) at 6 months. One thousand sixty-six consecutive patients with Glasgow Coma Scale scores of 8 or less during the first 24 h after injury were randomly divided into two groups. Data from the first group (n = 799) were used to develop the models; data from the second group (n = 267) were used to test the accuracy, sensitivity, and specificity of the models by comparing predicted and actual outcomes. The 6-month mortality rate was 63.5%. Our findings confirm the importance of age, Glasgow Coma Scale scores, and hypotension in predicting outcome. Using data available at 24 h improved the predictive power of both models compared with admission data; at both time points, however, the differences in the results obtained with the two models were negligible. We conclude that outcome (dead versus alive) at 6 months after severe head injury can be predicted with logistic regression or neural network models based on data available at 24 h. Critical therapeutic decisions, such as cessation of therapy, should be based on the patient's status 1 day after injury and only rarely on admission status alone.

Are acoustic neuromas encapsulated tumors?

In articles and chapters on the subject of acoustic neuroma, it is almost invariably stated that they are well-encapsulated tumors. During surgical procedures, blunt mechanical dissection defines a natural subsurface cleavage plane that leaves intact a several millimeter thick rind of tumor surface. Occasionally, as a concession to neural integrity, less than complete resection is elected, leaving behind this "capsular" remnant. To clarify the nature of the surface of acoustic neuromas and to test whether this long held description is indeed correct, a microscopic analysis of 10 surgical specimens was performed. A wedge was harvested from the free surface of the tumor in the mid cerebellopontine angle that included a large, undisturbed section of the tumor surface. Histologic analysis showed that for most of the tumor surface only an extremely thin (3 to 5 microm) layer of connective tissue envelops the tumor. Neoplastic Schwann cells, which extend essentially to the margin of the tumor, were found to be somewhat flattened and compressed in the vicinity of the surface. Although acoustic neuromas are surrounded by a continuous layer of connective tissue, it is so exceptionally thin (on average less than the diameter of a red blood cell) that its edge cannot be visualized intraoperatively by a surgeon. Because the pathologic definition of a capsule is a thick, enveloping layer of connective tissue that is both micro- and macroscopically evident, it must be concluded that acoustic neuromas are nonencapsulated, at least in the conventional sense of the term. The surface peel observed intraoperatively is surgically produced during tumor debulking by cleaving of the looser central component from the more compressed portion of neoplastic cells that lies immediately beneath the free margin of the lesion.

Predicting survival from head trauma 24 hours after injury: a practical method with therapeutic implications.

OBJECTIVE: To develop a method to predict long-term outcome after head injury and determine if outcome can be accurately predicted 24 hours after injury. DESIGN: A retrospective review was performed on a study cohort of 672 head-injured patients admitted in coma (Glascow Coma Scale score < or = 8) who remained comatose for at least 6 hours, survived more than 24 hours, and had 6-month outcome data available. Stepwise logistic regression analysis was used to determine which clinical variables predicted 6-month outcome. Statistically significant clinical predictors were combined into a single examination variable (MPX score), which reflected a rank-ordering of examinations from worst to best, which was then further weighted by patient age. The relation between 6-month outcome and MPX score at admission and 24 hours was plotted and analyzed. MEASUREMENT AND MAIN RESULTS: Age, best motor score, and pupillary reactivity at admission and 24 hours were significant predictors of outcome; extraocular motility was predictive at 24 hours only. Age was the most important independent predictor, followed by best motor score, pupillary reactivity, and extraocular motility. Combining these predictors into MPX score resulted in a set of graphs that reliably predicted long-term outcome. The 24-hour MPX data were better predictors of 6-month outcome and were more specific in predicting negative outcomes than admission data. CONCLUSIONS: The method is simple to use, relying on bedside neurologic examination and a single graph, but appears to predict long-term outcome accurately as early as 24 hours after head injury. If validated on other large series of patients, this method could provide an objective and practical basis for terminating care in patients unlikely to survive a head injury.

Purkinje cell vulnerability to mild traumatic brain injury.

In this study we examined the cerebellar response to mild traumatic brain injury by assessing microglial activation and Purkinje cell loss. Activated microglia were identified using the antibodies OX-42 and ED-1 as well as isolectin B4. The anti-Purkinje cell antibody PEP-19 was used to evaluate Purkinje cell loss after injury. The mechanism of cell injury was examined using a monoclonal antibody to the inducible 72-kDa heat shock protein. A monoclonal antibody to the N-terminal sequence of Fos was used as a marker for neuronal activation. There was progressive activation of microglia in the cerebellar vermis within a few days after forebrain injury. In coronal sections the processes of activated microglia were oriented in "stripes" perpendicular to the cortical surface. In sagittal sections the activated microglia were in irregularly shaped clusters or in a fan-like distribution that radiated from the Purkinje cell layer toward the cortical surface. There was a significant loss of Purkinje cells 7 days postinjury as compared to the control group. There was no evidence of induction of heat shock protein in the cerebellum. In addition, there was no evidence of induction of c-Fos protein in either the cerebellar cortex or inferior olivary nuclei within the first 3 h after injury. These studies demonstrate that a fluid percussive impact to the forebrain results in cerebellar damage. The close anatomical association between activated microglia and Purkinje cells suggests that Purkinje cell injury is the cause of the microglial activation. The mechanism of Purkinje cell death, however, remains unclear.

Intervertebral disc space infection caused by Aspergillus fumigatus.

The authors describe the case of a 53-year-old woman who suffered from an Aspergillus fumigatus infection of the L2/3 intervertebral disc space unrelated to previous operations on her lumbar spine. After surgical debridement combined with amphotericin therapy she died on the 23rd postoperative day from a fulminant bacterial sepsis of pulmonary origin. Although she had intermittently used steroids for bronchial asthma, this is an unusual case of fungal infection of the lumbar spine in an apparently immunocompetent patient.