Early induction of hypothermia for evacuated intracranial hematomas: a post hoc analysis of two clinical trials.

The authors hypothesized that cooling before evacuation of traumatic intracranial hematomas protects the brain from reperfusion injury and, if so, further hypothesized that hypothermia induction before or soon after craniotomy should be associated with improved outcomes.


The National Acute Brain Injury Study: Hypothermia I (NABIS:H I) was a randomized multicenter clinical trial of 392 patients with severe brain injury treated using normothermia or hypothermia for 48 hours with patients reaching 33°C at 8.4 ± 3 hours after injury. The National Acute Brain Injury Study: Hypothermia II (NABIS:H II) was a randomized, multicenter clinical trial of 97 patients with severe brain injury treated with normothermia or hypothermia for 48 hours with patients reaching 35°C within 2.6 ± 1.2 hours and 33°C within 4.4 ± 1.5 hours of injury. Entry and exclusion criteria, management, and outcome measures in the 2 trials were similar.


In NABIS:H II among the patients with evacuated intracranial hematomas, outcome was poor (severe disability, vegetative state, or death) in 5 of 15 patients in the hypothermia group and in 9 of 13 patients in the normothermia group (relative risk 0.44, 95% CI 0.22–0.88; p = 0.02). All patients randomized to hypothermia reached 35°C within 1.5 hours after surgery start and 33°C within 5.55 hours. Applying these criteria to NABIS:H I, 31 of 54 hypothermia-treated patients reached a temperature of 35°C or lower within 1.5 hours after surgery start time, and the remaining 23 patients reached 35°C at later time points. Outcome was poor in 14 (45%) of 31 patients reaching 35°C within 1.5 hours of surgery, in 14 (61%) of 23 patients reaching 35°C more than 1.5 hours of surgery, and in 35 (60%) of 58 patients in the normothermia group (relative risk 0.74, 95%, CI 0.49–1.13; p = 0.16). A meta-analysis of 46 patients with hematomas in both trials who reached 35°C within 1.5 hours of surgery start showed a significantly reduced rate of poor outcomes (41%) compared with 94 patients treated with hypothermia who did not reach 35°C within that time and patients treated at normothermia (62%, p = 0.009).


Induction of hypothermia to 35°C before or soon after craniotomy with maintenance at 33°C for 48 hours thereafter may improve outcome of patients with hematomas and severe traumatic brain injury. Clinical trial registration no.: NCT00178711.

Source: Journal of Neurosurgery.






Long-term radiosurgery effects in the treatment of temporal lobe epilepsy.

Epilepsy surgery is an effective treatment for medically resistant temporal lobe epilepsy (TLE). To minimize complication rates and potentially improve neuropsychology outcomes, stereotactic radiosurgery (SRS) has been explored as an alternative. Two pilot trials have demonstrated the effectiveness of SRS for the treatment of medically resistant TLE, with seizure-free outcomes for approximately 65% of patients at last follow-up. Despite encouraging results, no conclusive long-term outcomes are available for SRS. This article discusses a single patient who presented with recurrent seizures, worsening headaches, and persistent abnormal MRI findings 7 years and 8 months after SRS.

This 29-year-old woman with a history of medically refractory complex partial seizures since childhood was referred for evaluation. Medical management had failed in this patient. The workup was compatible with left mesial temporal lobe onset, with MRI findings suggestive of mesial temporal sclerosis. In 2003, at the age of 23 years, she underwent Gamma Knife surgery (GKS) targeting the left temporal mesial area with a dose of 24 Gy at the 50% marginal isodose line. After GKS, the patient’s seizures decreased in frequency over several months, but auras were persistent. Nine months after treatment, she developed worsening headaches. A follow-up MRI study demonstrated a thick, irregular, enhancing lesion in the medial part of the temporal lobe. She was placed on corticosteroids, with resolution of her headaches.

Her seizures and headaches recurred in March 2010. An MRI study showed a 2.2-cm, ill-defined, enhancing cystic lesion in the left mesial temporal lobe with T2 and FLAIR hyperintensity, which was presumably radiation induced. At that time, the patient opted for left temporal lobe resection to control her seizures. Histological examination showed moderately severe, remote, longstanding sclerosis at the level of the hippocampus. A vascular lesion was identified, and it was most consistent with radiation-induced capillary hemangioma. The entorhinal region was severely damaged, with hemorrhage, necrosis, neuronal loss, astrogliosis, and hemosiderin deposition. There was evidence of radiation vasculopathy.

Radiation-induced lesions after SRS for the treatment of epilepsy are not well documented. Although GKS is a promising technique for the treatment of medically resistant TLE, the ideal candidate is not yet well defined. The selection of the appropriate technical parameters to obtain a desirable functional effect without histological damage to the surrounding neural tissue remains a challenge. This case illustrates the need for long-term follow-up when radiosurgery is used for epilepsy.

Source: Journal of Neurosurgery.



A radiopathological classification of dural tail sign of meningiomas.

The completeness of meningioma resection depends on the resection of dura mater invaded by the tumor. The pathological changes of the dura around the tumor can be interpreted by evaluating the dural tail sign (DTS) on MRI studies. The goal of this study was to clarify the pathological characteristics of the DTSs, propose a classification based on the histopathological and radiological correlation, and identify the invasive range of tumor cells in different types of DTS.


The authors retrospectively reviewed 179 patients with convexity meningiomas who underwent Simpson Grade I resection. All patients underwent an enhanced MRI examination preoperatively. The convexity meningiomas were dichotomized into various subtypes in accordance with the 2007 WHO classification of tumors of the CNS, and the DTS was identified based on the Goldsher criteria. The range of resection of the involved dura was 3 cm from the base of the tumor, which corresponded with the length of DTS on MRI studies. Histopathological examination of dura at 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 cm from the base of the tumor was conducted, and the findings were correlated with the preoperative MRI appearance of the DTS.


A total of 154 (86%) of 179 convexity meningiomas were classified into WHO Grade I subtype, including transitional (44 [28.6%] of 154), meningothelial (36 [23.4%] of 154), fibrous (23 [14.9%] of 154), psammomatous (22 [14.3%] of 154), secretory (10 [6.5%] of 154), and angiomatous (19 [12.3%] of 154). The other 25 (14%) were non–Grade I (WHO) tumors, including atypical (12 [48%] of 25), anaplastic (5 [20%] of 25), and papillary (8 [32%] of 25). The DTS was classified into 5 types: smooth (16 [8.9%] of 179), nodular (36 [20.1%] of 179), mixed (57 [31.8%] of 179), symmetrical multipolar (15 [8.4%] of 179), and asymmetrical multipolar (55 [30.7%] of 179). There was a significant difference in distribution of DTS type between Grade I and non–Grade I tumors (p = 0.004), whereas the difference was not significant among Grade I tumors (0.841) or among non–Grade I tumors (p = 0.818). All smooth-type DTSs were encountered in Grade I tumors, and the mixed DTS (52 [33.8%] of 154) was the most common type in these tumors. Nodular-type DTS was more commonly seen in non–Grade I tumors (12 [48%] of 25). Tumor invasion was found in 88.3% (158 of 179) of convexity meningiomas, of which the range of invasion in 82.3% (130 of 158) was within 2 cm and that in 94.9% (150 of 158) was within 2.5 cm. The incidence of invasion and the range invaded by tumor cells varied in different types of DTS, and differences were statistically significant (p < 0.001).


Nodular-type DTS on MRI studies might be associated with non–Grade I tumors. The range of dural resection for convexity meningiomas should be 2.5 cm from the tumor base, and if this extent of resection is not feasible, the type of DTS should be considered. However, for skull base meningiomas, in which mostly Simpson Grade II resection is achieved, the use of this classification should be further validated. The classification of DTS enables the surgeon to predict preoperatively and then to achieve the optimal range of dural resection that might significantly reduce the recurrence rate of meningiomas.

Source: Journal of Neurosurgery.




How Many Transfers to Tertiary Pediatric EDs Are Unnecessary?

In a large study of children transferred to pediatric emergency departments in the U.S., 25% were directly discharged.

In a cross-sectional study of 22,891 emergency department (ED) patients <18 years of age (mean age, 6 years) transferred to 29 U.S. tertiary pediatric hospitals during 1 year, investigators examined common diagnoses and management of those who were discharged directly or admitted for <24 hours.

Of the 5645 patients who were discharged directly from the tertiary ED, 21% required no additional testing, procedures, or medications. An additional 33% received only acetaminophen, ibuprofen, ondansetron, or plain radiographs. The top five diagnostic categories for patients discharged directly were orthopedic problems (16%), nonsurgical abdominal pain (6%), viral gastroenteritis and dehydration (6%), gastrointestinal illness (5%), and traumatic head injury (5%). The authors recommend educational efforts for general ED providers about common pediatric complaints.

Comment: The authors erroneously (and arrogantly) failed to include in the study’s limitations the complete lack of follow-up data on discharged patients. Rather, they assumed no adverse outcomes and used the clinical impression of the physician at the tertiary pediatric ED as its own gold standard. These results may be useful to advocate for more pediatric-specific resources and specialty services across the U.S., but should not be used to preach about the (unfounded) ignorance of general ED providers.

Source: Journal Watch Emergency Medicine.

Silymarin Is Ineffective for Chronic Hepatitis C Virus Infection.

In the most rigorous trial to date, oral silymarin was not superior to placebo in decreasing disease activity.

Silymarin is a botanical extract of milk thistle commonly used by patients with liver disease. In vitro studies have demonstrated antiviral, anti-inflammatory properties of silymarin in hepatitis C virus (HCV) replicon systems. However, the few efficacy studies conducted in patients with chronic HCV infection have produced mixed results.

In a new multicenter, double-blind, placebo-controlled efficacy trial, investigators randomized 154 patients (median age, 54; 71% men) with chronic HCV infection who previously failed interferon-based therapy to receive 420 mg of silymarin, 700 mg of silymarin, or placebo three times daily for 24 weeks. The two oral doses of pure silymarin were determined by earlier dose finding studies and were three to five times higher than concentrations used in previous studies. The primary endpoint was a serum alanine aminotransferase (ALT) level of 45 U/L or a 50% reduction from baseline ALT to a level <65 U/L. Secondary endpoints included HCV RNA levels and quality-of-life indicators.

After 24 weeks of treatment, only two patients in each group achieved the primary endpoint. The mean decline in ALT levels at the end of treatment, the mean change in HCV RNA levels, and the quality-of-life indicators did not differ among the three groups.

Comment: This trial definitively demonstrates that silymarin, even at three to five times the typical dose, is ineffective in treating patients with chronic HCV infection. Unlike previous trials, this study used a pure, quantifiable formulation of silymarin and well-defined outcomes, its cohort was large and representative of the patient population, the treatment period was sufficiently long, and both medication and visit adherence rates were high. Clinicians should quote this study when addressing patients’ questions regarding the use of milk thistle for treating HCV infection.

Source: Journal Watch Gastroenterology