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  • Author or Editor: C. David Weaver x
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David S. Ditor, Sunil John, Jason Cakiroglu, Colin Kittmer, Paula J. Foster and Lynne C. Weaver

Object

The purpose of this study was to compare measures of lesion volume obtained by means of 1.5-T MR imaging to those obtained by the Cavalieri method, 6 weeks after experimental spinal cord injury.

Methods

Nine male Wistar rats were subjected to spinal cord injury by clip compression (50 g) at the T-4 level. Six weeks postinjury, the rats were sacrificed, and spinal cords were analyzed ex vivo for lesion volume by means of 1.5-T MR imaging and subsequently, by the Cavalieri method. In the latter method, cords were cut longitudinally in 25-μm sections and stained with solochrome cyanin for myelin. The area of the lesion was determined for each serial section, and the distance-weighted sum of all area measures was then calculated to estimate the total lesion volume.

Results

Bland–Altman analysis showed that the 2 methods had an acceptable level of agreement for lesion volume estimation, but the Cavalieri method was prone to an overestimation bias. The MR imaging estimates of lesion volume were greater than the Cavalieri method estimates in 3 spinal cords, but the difference between measures was within 1 standard deviation of perfect agreement in these 3 lesions, and the mean difference between measures was 18.3%. In contrast, in those lesions in which the Cavalieri method yielded larger lesion volumes (5 lesions), the difference between measures was 2 standard deviations away from perfect agreement for 2 animals and the mean difference between measures was 72.4%.

Conclusions

The results illustrate that the overestimation bias of the Cavalieri method is due, in part, to artifacts produced during processing of the spinal cord tissue.

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S. Scott Lollis, P. Jack Hoopes, Susan Kane, Keith Paulsen, John Weaver and David W. Roberts

Object

Intracisternal injection of kaolin is a well-described model of feline hydrocephalus. Its principal disadvantage is a high rate of procedure-related morbidity and mortality. The authors describe a series of modifications to a commonly used protocol, intended to ameliorate animal welfare concerns without compromising the degree of ventricular enlargement.

Methods

In 11 adult cats, hydrocephalus was induced by injection of kaolin into the cisterna magna. Kaolin doses were reduced to 10 mg, compared with historical doses of ~ 200 mg, and high-dose dexamethasone was used to reduce the severity of meningeal irritation. A control cohort of 6 additional animals received injections of isotonic saline into the cisterna magna.

Results

The mean ventricular volume increased from a baseline of 0.183 ± 0.068 ml to 1.43 ± 0.184 ml. Two animals were killed prior to completion of the study. Of the remaining animals, all were ambulatory by postinjection Day 1, and all had resumed normal oral intake by postinjection Day 3. Two animals required subcutaneous fluid supplementation. Ventriculostomy using anatomical landmarks was performed to ascertain intraventricular pressure. The mean intraventricular pressure after hydrocephalus was 15 cm H2O above the ear (range 11–20 cm H2O).

Conclusions

Reduction in kaolin dosage and the postoperative administration of high-dose corticosteroid therapy appear to reduce morbidity and mortality rates compared with historical experiences. Hydrocephalus is radiographically evident as soon as 3 days after injection, but it does not substantially interfere with feeding and basic selfcare. To the extent that animal welfare concerns may have limited the use of this model in recent years, the procedures described in the present study may offer some guidance for its future use.

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David S. Ditor, Feng Bao, Yuhua Chen, Gregory A. Dekaban and Lynne C. Weaver

Object

The purpose of this study was to investigate the therapeutic time window for antiinflammatory treatment within the first 24 hours of spinal cord injury (SCI). The authors have shown that an anti-CD11d antibody treatment attenuates leukocyte infiltration and improves neurological function when administered beginning 2 hours after SCI. A more clinically relevant time for the initiation of treatment after SCI, however, is 6 or more hours postinjury.

Methods

In Study 1, the T-4 vertebrae in four groups of rats were injured by a 50-g clip-induced compression method, and the anti-CD11d antibody (1 mg/kg) was intravenously administered starting 2, 6, 12, or 24 hours postinjury. All groups received subsequent doses at 24 and 48 hours, and animals were killed at 72 hours. The anti-CD11d antibody treatment starting at 6 hours postinjury caused significant attenuation of leukocyte infiltration, reactive oxygen species–associated enzymes, and secondary tissue damage. Based on these findings, Study 2 included two groups of rats receiving the aforementioned injury and treatment beginning at 6 hours postinjury (with subsequent treatments at 24 and 48 hours) with the anti-CD11d or a control antibody (1B7); these rats were then observed for 5 weeks. Basso-Beattie-Bresnahan (BBB) scores were significantly higher in anti-CD11d–treated rats (mean BBB score 8.9 ± 0.1) than controls (mean BBB score 7.7 ± 0.1) 5 weeks postinjury. Increases in mean arterial pressure during colon distension were smaller in anti-CD11d–treated rats (19.5 ± 3.7 mm Hg) than in controls (37.4 ± 4.7 mm Hg).

Conclusions

These findings suggest that antiinflammatory treatments that reduce secondary tissue damage after SCI may be delayed until 6 hours postinjury and still be effective.

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Matthew L. Carlson, William R. Copeland III, Colin L. Driscoll, Michael J. Link, David S. Haynes, Reid C. Thompson, Kyle D. Weaver and George B. Wanna

Object

The goals of this study were to report the clinical presentation, radiographic findings, operative strategy, and outcomes among patients with temporal bone encephaloceles and cerebrospinal fluid fistulas (CSFFs) and to identify clinical variables associated with surgical outcome.

Methods

A retrospective case series including all patients who underwent a middle fossa craniotomy or combined mastoid–middle cranial fossa repair of encephalocele and/or CSFF between 2000 and 2012 was accrued from 2 tertiary academic referral centers.

Results

Eighty-nine consecutive surgeries (86 patients, 59.3% women) were included. The mean age at time of surgery was 52.3 years, and the left side was affected in 53.9% of cases. The mean delay between symptom onset and diagnosis was 35.4 months, and the most common presenting symptoms were hearing loss (92.1%) and persistent ipsilateral otorrhea (73.0%). Few reported a history of intracranial infection (6.7%) or seizures (2.2%).

Thirteen (14.6%) of 89 cases had a history of major head trauma, 23 (25.8%) were associated with chronic ear disease without prior operation, 17 (19.1%) occurred following tympanomastoidectomy, and 1 (1.1%) developed in a patient with a cerebral aqueduct cyst resulting in obstructive hydrocephalus. The remaining 35 cases (39.3%) were considered spontaneous. Among all patients, the mean body mass index (BMI) was 35.3 kg/m2, and 46.4% exhibited empty sella syndrome. Patients with spontaneous lesions were statistically significantly older (p = 0.007) and were more commonly female (p = 0.048) compared with those with nonspontaneous pathology. Additionally, those with spontaneous lesions had a greater BMI than those with nonspontaneous disease (p = 0.102), although this difference did not achieve statistical significance.

Thirty-two surgeries (36.0%) involved a middle fossa craniotomy alone, whereas 57 (64.0%) involved a combined mastoid–middle fossa repair. There were 7 recurrences (7.9%); 2 patients with recurrence developed meningitis. The use of artificial titanium mesh was statistically associated with the development of recurrent CSFF (p = 0.004), postoperative wound infection (p = 0.039), and meningitis (p = 0.014). Also notable, 6 of the 7 cases with recurrence had evidence of intracranial hypertension. When the 11 cases that involved using titanium mesh were excluded, 96.2% of patients whose lesions were reconstructed with an autologous multilayer repair had neither recurrent CSFF nor meningitis at the last follow-up.

Conclusions

Patients with temporal bone encephalocele and CSFF commonly present with persistent otorrhea and conductive hearing loss mimicking chronic middle ear disease, which likely contributes to a delay in diagnosis. There is a high prevalence of obesity among this patient population, which may play a role in the pathogenesis of primary and recurrent disease. A middle fossa craniotomy or a combined mastoid–middle fossa approach incorporating a multilayer autologous tissue technique is a safe and reliable method of repair that may be particularly useful for large or multifocal defects. Defect reconstruction using artificial titanium mesh should generally be avoided given increased risks of recurrence and postoperative meningitis.