Lawrence H. Pitts

Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination.

We have examined the incidence and size of infarction after occlusion of different portions of the rat middle cerebral artery (MCA) in order to define the reliability and predictability of this model of brain ischemia. We developed a neurologic examination and have correlated changes in neurologic status with the size and location of areas of infarction. The MCA was surgically occluded at different sites in six groups of normal rats. After 24 hr, rats were evaluated for the extent of neurologic deficits and graded as having severe, moderate, or no deficit using a new examination developed for this model. After rats were sacrificed the incidence of infarction was determined at histologic examination. In a subset of rats, the size of the area of infarction was measured as a percent of the area of a standard coronal section. Focal (1-2 mm) occlusion of the MCA at its origin, at the olfactory tract, or lateral to the inferior cerebral vein produced infarction in 13%, 67%, and 0% of rats, respectively (N = 38) and produced variable neurologic deficits. However, more extensive (3 or 6 mm) occlusion of the MCA beginning proximal to the olfactory tract--thus isolating lenticulostriate end-arteries from the proximal and distal supply--produced infarctions of uniform size, location, and with severe neurologic deficit (Grade 2) in 100% of rats (N = 17). Neurologic deficit correlated significantly with the size of the infarcted area (Grade 2, N = 17, 28 +/- 5% infarction; Grade 1, N = 5, 19 +/- 5%; Grade 0, N = 3, 10 +/- 2%; p less than 0.05). We have characterized precise anatomical sites of the MCA that when surgically occluded reliably produce uniform cerebral infarction in rats, and have developed a neurologic grading system that can be used to evaluate the effects of cerebral ischemia rapidly and accurately. The model will be useful for experimental assessment of new therapies for irreversible cerebral ischemia.

Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats.

We have evaluated the use of 2,3,5-triphenyltetrazolium chloride (TTC) as an histopathologic stain for identification of infarcted rat brain tissue. The middle cerebral artery (MCA) of 35 normal adult rats was occluded surgically. At various times after surgical occlusion, rats were sacrificed and brain slices were obtained and stained with TTC or hematoxolin and eosin (H & E); the size of the area of infarcted tissue stained by each method was quantified. In rats sacrificed 24 hr after occlusion of the MCA, the size of the area of infarction was 21 +/- 2% of the coronal section for TTC, and 21 +/- 2% for H & E (mean +/- S.D., N = 13). The size of areas of infarction determined by either staining method was not significantly different in area by the paired test, and a significant correlation between sizes determined by each method was found by linear regression analysis (r = 0.91, slope = 0.89, and the y intercept = 4.4%). Staining with TTC is a rapid, convenient, inexpensive, and reliable method for the detection and quantification of cerebral infarction in rats 24 hr after the onset of ischemia.

Five year results of linac radiosurgery for arteriovenous malformations: outcome for large AVMS

PURPOSE For radiosurgery of large arteriovenous malformations (AVMs), the optimal relationship of dose and volume to obliteration, complications, and hemorrhage is not well defined. Multivariate analysis was performed to assess the relationship of multiple AVM and treatment factors to the outcome of AVMs significantly larger than previously reported in the literature. METHODS AND MATERIALS 73 patients with intracranial AVMs underwent LINAC radiosurgery. Over 50% of the AVMs were larger than 3 cm in diameter and the median and mean treatment volumes were 8.4 cc and 15.3 cc, respectively (range 0.4-143.4 cc). Minimum AVM treatment doses varied between 1000-2200 cGy (median: 1600 cGy). RESULTS The obliteration rates for treatment volumes < 4 cc, 4-13.9 cc, and > or = 14 cc were 67%, 58%, and 23%, respectively. AVM obliteration was significantly associated with higher minimum treatment dose and negatively associated with a history of prior embolization with particulate materials. No AVM receiving < 1400 cGy was obliterated. The incidence of post-radiosurgical imaging abnormalities and clinical complications rose with increasing treatment volume. For treatment volumes > 14 cc receiving > or = 1600 cGy, the incidence of post-radiosurgical MRI T2 abnormalities was 72% and the incidence of radiation necrosis requiring resection was 22%. The rate of post-radiosurgical hemorrhage was 2.7% per person-year for AVMs with treatment volumes < 14 cc and 7.5% per person-year for AVMs > or = 14 cc. CONCLUSION As AVM size increases, the dose-volume range for the optimal balance between successful obliteration and the risk of complications and post-radiosurgical hemorrhage narrows.

Evaluation of 2,3,5-triphenyltetrazolium chloride staining to delineate rat brain infarcts.

Background and Purpose: Accurate and reproducible determination of the size and location of cerebral infarcts is critical for the evaluation of experimental focal cerebral ischemia. The purpose of this study was to compare intracardiac perfusion of 2,3,5-triphenyltetrazolium chloride with immersion of brain tissue in 2,3,5-triphenyltetrazolium chloride to delineate brain infarcts in rats. Methods: After 6, 24, or 48 hours of ischemia induced by permanent middle cerebral artery occlusion, some rats were perfused with 2,3,5-triphenyltetrazolium chloride; other rats were given an overdose of barbiturates, after which brain sections were immersed in 2,3,5- triphenyltetrazolium chloride. Coronal sections were taken 4, 6, and 8 mm from the frontal pole, and infarct areas in perfused and immersed sections were compared; subsequently, the same sections were stained with hematoxylin and eosin. Results: In rats subjected to 24 or 48 hours of occlusion, areas of infarction were clearly defined with both 2,3,5-triphenyltetrazolium chloride staining techniques, and the infarct sizes correlated well with the results of hematoxylin and eosin staining (r=0.85−0.94). Conclusions: These results demonstrate that intracardiac perfusion of 2,3,5-triphenyltetrazolium chloride is an accurate, inexpensive, and efficient staining method to detect infarcted tissue 24 and 48 hours after the onset of ischemia in rats.

The Effect of Hypoxia on Traumatic Head Injury in Rats: Alterations in Neurologic Function, Brain Edema, and Cerebral Blood Flow

We evaluated the effects of early posttraumatic hypoxia on neurologic function, magnetic resonance images (MRI), brain tissue specific gravities, and cerebral blood flow (CBF) in head-injured rats. By itself, an hypoxic insult (PaO2 40 mm Hg for 30 min) had little effect on any measure of cerebral function. After temporal fluid-percussion impact injury, however, hypoxia significantly increased morbidity. Of rats subjected to impact (4.9 ± 0.3 atm) plus hypoxia, 71% had motor weakness contralateral to the impact side 24 h after injury, while only 29% of rats subjected to impact alone had demonstrable weakness (p < 0.05). Lesions observed on MR images 24 h after injury were restricted to the impact site in rats with impact injury alone, but extensive areas with longer T1 relaxation times were observed throughout the ipsilateral cortex in rats with impact injury and hypoxic insult. Brain tissue specific gravity measurements indicated that much more widespread and severe edema developed in rats with impact injury and hypoxia. [14C]Iodoantipyrine autoradiography performed 24 h after injury showed that there was extensive hypoperfusion of the entire ipsilateral cortex in rats with impact injury and hypoxia. These results show that large areas of impact-injured brain are extremely vulnerable to secondary insults that can irreparably damage neural tissue, and provide experimental evidence for the observed adverse effects of hypoxia on outcome after human head injury.

Effect of hypoxia on traumatic brain injury in rats: Part 1. Changes in neurological function, electroencephalograms, and histopathology.

The effect of hypoxia on neurological function, compressed spectral array electroencephalography, and histopathology in head-injured rats was evaluated. By itself, an hypoxic insult (PaO2, 40 mm Hg for 30 minutes) caused no neurological deficit. Twenty per cent of rats injured by a 5-atmosphere temporal fluid percussion impact were hemiparetic contralateral to the side of impact, whereas 80% had no deficit 24 hours after injury. Seventy per cent of rats with both fluid impact injury and hypoxic insult, however, either had a definite hemiparesis, showed no spontaneous movement, or died (P less than 0.02). Impact alone produced an initial depression in electroencephalogram power that was prolonged in rats with hypoxic insult; the most dramatic effect was found in the injured hemisphere, with shorter and less profound effects in the contralateral hemisphere. Perfusion staining of injured cerebral tissue in vivo with 2,3,5-triphenyltetrazolium chloride showed an area of extensive ischemia around the impact site in rats with hypoxic insult. This ischemic area was not present in rats with either impact injury or hypoxia alone. We conclude that posttraumatic hypoxia clearly increases the severity of impact injury in this rat model. These findings suggest that hypoxia, which is common in head-injured patients, very likely worsens the effect of impact injury and may account for much of the diffuse neurological dysfunction in patients with severe craniocerebral trauma.

The Fate of the Tumor Remnant after Less-than-Complete Acoustic Neuroma Resection

OBJECTIVES: We sought to determine the recurrence rate after near-total and subtotal resection of acoustic neuroma. STUDY DESIGN, SETTING, AND PATIENTS: We conducted a retrospective chart review of a total of 79 patients: 50 with near-total resections (remnant ≤ 25 mm 2 and ≤ 2 mm thick) and 29 with subtotal resections (any larger remnant). Surgical approach included 5 middle fossa, 17 retrosigmoid, and 57 translabyrinthine. MAIN OUTCOME MEASURES: Recurrence was defined as documented tumor growth by serial imaging or the recommendation for further treatment after a single scan. No recurrence was defined as no visible tumor on imaging for a minimum follow-up time of 3 years or tumor remnants that remained unchanged on serial scans (mean, 5-year follow-up). RESULTS: Fifty-two patients were included in the study group. Recurrences were seen in 1 (3%) of 33 patients who had a near-total resection compared with 6 (32%) of 19 patients who had a subtotal resection. After adjustment for follow-up time and large tumor size, the odds ratio for recurrence was 12 times larger for subtotal than for near-total resections (P = 0.033). All recurrences were seen following the translabyrinthine approach in the mid-cerebellopontine angle. None were encountered in the internal auditory canal. The mean time interval from surgery to the detection of a recurrence was 3 years (range, 1 to 5 years). CONCLUSIONS: The recurrence rate when performing a near-total resection is low but is substantially higher with a subtotal resection. Recurrences can be detected within the first 5 postoperative years. We recommend near-total resection in any patient if needed to preserve neural integrity. Subtotal resection is best avoided whenever possible; however, adjunctive treatment with stereotactic radiotherapy may be considered.

Traumatic intracerebral hematomas: timing of appearance and indications for operative removal.

Immediate and delayed traumatic intracerebral hematomas (ICH) can produce devastating secondary brain damage after severe head injury. The relationship between the initial injury and eventual occurrence, size, and time of appearance of such hematomas is not well understood, but has great importance since delayed appearance may necessitate delayed surgical decompression of developing lesions not present on early CT scans. We reviewed the records of 35 consecutive patients with operated post-traumatic ICH to document when these lesions appeared on CT, what were the indications for surgery, and what was eventual outcome. Time between injury and ICH appearance was categorized as immediate (0-3 hours), intermediate (3-6), delayed (6-24) or very delayed (later than 24 hours). ICH appearance was immediate in 20%, intermediate in 6%, delayed in 29%, and very delayed in 46%. Half of the patients were not comatose at the time of admission (GCS greater than or equal to 8). Hematoma removal was prompted by clinical deterioration or failure to improve in half the patients and by uncontrolled intracranial hypertension in the other half. Half the patients died, generally those in traumatic coma immediately after injury although advanced age also was associated with poor outcome. Only about one quarter of patients who require surgical removal of ICH can be shown to have their lesions soon after injury. Most operable intraparenchymal clots develop after initial CT scanning and trauma surgeons must be prepared to recognize and treat this delayed complication of brain injury. Even with aggressive management, ICH contribute significantly to poor outcome and improved treatment must be sought.

Cerebrospinal fluid leak after acoustic neuroma surgery: a comparison of the translabyrinthine, middle fossa, and retrosigmoid approaches.

Objective To determine whether the choice of surgical approach affects the rate of postoperative cerebrospinal fluid leakage in patients who have undergone surgical resection of acoustic neuroma. Study Design Retrospective chart review. Setting Tertiary referral center. Patients Three hundred patients who underwent surgery for acoustic neuromas were selected by consecutive medical record number until 100 resections via each surgical approach (translabyrinthine, middle fossa, and retrosigmoid) had been gathered. Main Outcome Measures Surgical approach used, cerebrospinal fluid leak incidence, tumor size, patient age. Results Postoperative cerebrospinal fluid leak of any severity was observed in 13% of translabyrinthine, 10% of middle fossa, and 10% of retrosigmoid patients. These difference in the rate of cerebrospinal fluid leakage were not statistically significant (p = 0.82). The majority of leaks were managed conservatively with fluid and activity restriction, often accompanied by a period of lumbar subarachnoid drainage. There was a need to return to the operating room for a definitive procedure in 4% of translabyrinthine, 2% of middle fossa, and 3% retrosigmoid patients; again not statistically different among the approaches (p = 0.43). Tumor size was not correlated with cerebrospinal fluid leak rate (p = 0.13). Patient age, for patients older than 50 years, was suggestive of increased odds of cerebrospinal fluid leak (p = 0.06). Conclusion Neither surgical approach nor tumor size affects the rate of postoperative cerebrospinal fluid leakage or the necessity of managing a leak with a return to the operating room. Cerebrospinal fluid leakage rates have remained stable in recent decades despite numerous innovative attempts to improve dural closure, seal transected air cell tracts, and occlude anatomic pathways. The finding that leak rates were similar among three dissimilar surgical techniques suggests that factors other than techniques of wound closure, such as transient postoperative rises in cerebrospinal fluid pressure, may be responsible for these recalcitrant cases.

Complications of lumboperitoneal shunts

OBJECTIVEPlacement of a lumboperitoneal (LP) shunt is a method for treating communicating hydrocephalus. These shunts can be placed with or without valves. We sought to review the complications associated with the use of LP shunts with the increasing use of horizontal-vertical (HV) valve systems. PATIENTS AND METHODSA retrospective chart review of all patients who received LP shunts at University of California, San Francisco from 1998 to 2005 was performed. RESULTSOf the 74 patients identified in this study, 67 underwent LP shunt placement for the first time, and seven patients had revisions of LP shunts that were originally placed at another hospital. There were a total of 44 revisions for the entire group: 27 patients had one revision, 10 patients had two or three revisions, and one patient had five revisions. Obstruction or migration of the peritoneal catheter was the most common reason for revision. The HV valve was responsible for shunt malfunction in nine patients and was the second-most common site of system problems. Overdrainage symptoms were observed in 11 patients, most of whom had LP shunts without any valve. No patients with an HV valve system developed an acquired Chiari malformation. There were three cases of infection, two of which required removal of the LP shunt. CONCLUSIONOverall, the placement of LP shunts for the treatment of communicating hydrocephalus seems to be a safe procedure. Serious complications such as subdural hematoma were not observed. The HV valve was associated with minor complications, but it was effective in reducing the incidence of overdrainage.