Prospective comparative study of intraoperative balloon electronic brachytherapy versus resection with multidisciplinary adjuvant therapy for recurrent glioblastoma.

BACKGROUND: Intraoperative balloon electronic brachytherapy (IBEB) may provide potential benefit for local control of recurrent cerebral glioblastomas (GBMs). METHODS: This is a preliminary report of an open-label, prospective, comparative cohort study conducted in two neurosurgical centers with ongoing follow-up. At recurrence, patients at one center (n = 15) underwent reresection with IBEB while, at the second center (n = 15), control subjects underwent re-resection with various accepted second-line adjuvant chemoradiotherapy options. A comparative analysis of overall survival (OS) and local progression-free survival (LPFS) following re-resection was performed. Exploratory subgroup analysis based on postoperative residual contrast-enhanced volume status was also done. RESULTS: In the IBEB group, median LPFS after re-resection was significantly longer than in the control group (8.0 vs. 6.0 months; log rank χ2 = 4.93, P = 0.026, P < 0.05). In addition, the median OS after second resection in the IBEB group was also significantly longer than in the control group (11.0 vs. 8.0 months; log rank χ2 = 4.23, P = 0.04, P < 0.05). CONCLUSION: These hypothesis-generating results from a small cohort of subjects suggest putative clinical benefit in OS and LPFS associated with maximal safe re-resection of recurrent GBM with IBEB versus re-resection and standard adjuvant therapy, a hypothesis that deserves further testing in an appropriately powered clinical trial.

Repeat Resection and Intraoperative Radiotherapy for Malignant Gliomas of the Brain: A History and Review of Current Techniques.

The degree of primary resection of malignant brain gliomas (MBGs) has correlated positively with progression-free and overall survival. The indications for surgery and reoperation in MBG relapse remain controversial. Surgery will not be curative and should be followed by adjuvant treatment. We reviewed the reported studies with respect to repeat resection and the various methods of intraoperative radiotherapy for MBGs from the initial experience with high-energy linear accelerators in Japan to modern, integrated brachytherapy solutions using solid and balloon applicators. Because of the findings from our review, we have begun to research into the use of intraoperative balloon brachytherapy for recurrent MBGs.

Symptomatic tension pneumocephalus following Palacos® cranioplasty in a shunted patient.

Tension pneumocephalus is an exceedingly rare complication of cerebrospinal fluid diversion occurring after surgery, trauma or spontaneous fistula formation. We report a case in a patient with a ventriculoperitoneal shunt who developed symptomatic tension pneumocephalus via a skin defect within 24 hours of undergoing bone cement cranioplasty.

Cerebrospinal Fluid Presepsin As a Marker of Nosocomial Infections of the Central Nervous System: A Prospective Observational Study.

BACKGROUND: Nosocomial CNS infection (NI-CNS) is a common and serious complication in neurocritical care patients. Timely, accurate diagnosis of NI-CNS is crucial, yet current infection markers lack specificity and/or sensitivity. Presepsin (PSP) is a novel biomarker of macrophage activation. Its utility in NI-CNS has not been explored. We first determined the normal range of cerebrospinal fluid (CSF) PSP in a control group without brain injury before collecting data on CSF PSP levels in neurocritical care patients. Samples were analyzed in four groups defined by systemic and neurological infection status. RESULTS: CSF PSP levels in 15 control patients without neurological injury were 50-100 pg/ml. Ninety-seven CSF samples were collected from 21 neurocritical care patients. In patients without NI-CNS or systemic infection, CSF PSP was 340.4 ± 201.1 pg/ml. Isolated NI-CNS was associated with CSF PSP levels of 640.8 ± 235.5 pg/ml, while levels in systemic infection without NI-CNS were 580.1 ± 329.7 pg/ml. Patients with both NI-CNS and systemic infection had CSF PSP levels of 1,047.7 ± 166.2 pg/ml. In neurocritical care patients without systemic infection, a cut-off value of 321 pg/ml gives sensitivity and specificity for NI-CNS of 100 and 58.3%, respectively. CONCLUSION: CSF PSP may prove useful in diagnosing NI-CNS, but its current utility is as an additional marker only.

Brain Tumor in an In Vitro Fertilization-Facilitated Pregnancy: Fourth Ventricle Anaplastic Ependymoma in the Second Trimester.

We present a case of fourth ventricle anaplastic ependymoma in a pregnancy which was the first result of three rounds of in vitro fertilization (IVF) and embryo transfer. Whether hormonal treatment can directly or indirectly precipitate brain tumors to develop or become symptomatic is unclear.

High-cervical spinal cord stimulation for medically intractable chronic migraine.

OBJECTIVES: High-cervical spinal cord stimulation (SCS) is a promising neurostimulation method for the control of chronic pain, including chronic cluster headache. The effects of high-cervical SCS in patients with intractable chronic migraine pain are unknown. MATERIALS AND METHODS: This study is a retrospective survey of a cohort of 17 consecutive patients with medically intractable chronic migraine pain implanted with a high-cervical SCS device between 2007 and 2011. RESULTS: After a median of 15 months (range 2-48) since implantation, mean pain intensity was significantly reduced by 60% (p < 0.0001), with 71% of the patients experiencing a decrease of 50% or more. The median number of days with migraine decreased from 28 (range 12-28) to 9.0 (range 0-28) days (p = 0.0313). Quality of life was significantly improved (p = 0.0006), and the proportion of patients not requiring pain medication increased from 0.0% to 37.5% (p = 0.0313). Use of pharmacological and nonpharmacological treatments of migraine was decreased. Working capacity was not significantly improved. Complications were infrequent: three infections (13.0% of all implanted) and three lead dislocations (17.6% of all included). CONCLUSION: In patients with intractable chronic migraine treated with high-cervical SCS, pain and quality of life significantly improved, warranting further research.

The supraorbital endoscopic approach for aneurysms.

OBJECTIVE: To review our surgical experience in minimally invasive transcranial endoscope-assisted microsurgical treatment of intracranial aneurysms, using the supraorbital keyhole craniotomy. METHODS: The supraorbital keyhole approach was performed through an eyebrow skin incision in 793 cases for treatment of 989 intracranial aneurysms. Of patients, 474 were operated on after subarachnoid hemorrhage, and 319 were operated on under elective conditions. After lateral frontobasal burr hole trephination, a limited subfrontal craniotomy was created. To achieve adequate intraoperative exposure through the limited approach, endoscopes were used routinely. Surgical outcome was assessed using the modified Rankin scale. RESULTS: The transcranial endoscope-assisted microneurosurgery technique was used routinely via a supraorbital approach. In 152 operations (19.1%), the endoscope provided important visual information in the vicinity of the aneurysm, revealing subsequent clip repositioning. The results of incidental aneurysms were excellent with a modified Rankin scale score ≤2 in 96.52%. The overall outcome of ruptured aneurysms was good with a modified Rankin scale score ≤2 in 72.2% of patients. There were no approach-related intraoperative or postoperative complications. CONCLUSIONS: The minimally invasive supraorbital keyhole approach allowed safe surgical treatment of intracranial aneurysms, including after subarachnoid hemorrhage. The markedly improved endoscopic visualization increased the assessment of clip placement with ideal control of surrounding vessels including perforators for identification of incorrect clip position.

Postsurgical meningitis complicated by severe refractory intracranial hypertension with limited treatment options: the role of mild therapeutic hypothermia.

Intracranial hypertension is a commonly encountered neurocritical care problem. If first-tier therapy is ineffective, second-tier therapy must be initiated. In many cases, the full arsenal of established treatment options is available. However, situations occasionally arise in which only a narrow range of options is available to neurointensivists. We present a rare clinical scenario in which therapeutic hypothermia was the only available method for controlling intracranial pressure and that demonstrates the efficacy and safety of the Thermogard (Zoll, Chelmsford, Massachusetts, United States) cooling system in creating and maintaining a prolonged hypothermic state. The lifesaving effect of hypothermia was overshadowed by the unfavorable neurologic outcome observed (minimally conscious state on intensive care unit discharge). These results add further evidence to support the role of therapeutic hypothermia in managing intracranial pressure and provide motivation for finding new strategies in combination with hypothermia to improve neurologic outcomes.

Extradural spinal cavernous malformation: a rare but important mimic.

Purely extradural spinal cavernous malformations (ESCMs) are rare, but the number of cases reported seems to be increasing. A 44-year-old woman presented with progressive cervicothoracic back pain, lower limb paraesthesia and hypertonia. MRI showed a well-circumscribed, convex lesion in the T1-4 extradural space causing cord compression and encroaching into the left T2/3 neural foramen. Selective spinal angiography demonstrated a vascular blush at the T2/T3 level corresponding with the mass. A feeding vessel arising from the base of the T1 spinous process was identified and successfully catheterised, but embolisation was precluded by unfavourable anatomy of the posterior spinal artery. At hemilaminectomy, the lesion was found to be an ESCM. The patient went on to make a full recovery. We reviewed 71 cases of ESCM reported in the last decade. Incidence of ESCM is unclear; the largest case series reported on nine patients, but most published accounts were single case studies. Patients presented with back pain (33%), myelopathy (56%) and/or radiculopathy (39%). Onset of symptoms was usually insidious over months to years, but 30% presented with sudden-onset neurological symptoms, often due to spontaneous haemorrhage. Mean age at diagnosis was 44 (range, 2-74; SD, 19.6) years with a 1:1 sex ratio. Lesions were found at all levels except C1-C2, but a strong predilection for the dorsal thoracic spine (68%) was shown. The lesion extended into an intravertebral foramen in at least 24 cases (34%). MRI is the investigation of choice, and angiography of ESCM has rarely been described. Most (87%) were hypo- to isointense on T1 MRI while hyperintensity on T2 (91%) and avid (89%), usually homogenous gadolinium update was almost universal. Perilesional haemosiderin, characteristic of intracranial and intramedullary cavernous malformation was rarely seen. In many cases, meningioma or nerve sheath tumour was misdiagnosed prior to surgery. All patients underwent total (95%) or subtotal (5%) microsurgical resection with excellent results; all improved (23%) or recovered fully (77%) after surgery. Those who presented acutely did worse; 38% had residual deficits.

The neuro-behavioral profile in rats after subarachnoid hemorrhage.

Despite significant advancements in the understanding of the pathophysiological mechanisms of subarachnoid hemorrhage (SAH), little is known about the emotional consequences. The primary goal of this study was to describe the locomotor and behavioral patterns in rats following both a single-injection and double-injection model of SAH. In 48 rats, SAH was induced by injecting 0.3 ml of autologous arterial blood into the cisterna magnum (single-hemorrhagic model). In 24 of these rats, post-SAH vasospasm was induced by a repeated injection of blood into the cisterna magnum 24h later (double-hemorrhagic model). In 24 additional rats, 0.3 ml of saline was injected into the cisterna magnum (sham group). Neurological performance was assessed at 24, 48 h, 1, 2 and 3 weeks after SAH. Four behavioral tests were performed for 3 weeks after SAH for the duration of 6 consequent days, in the following order: open field test, sucrose preference test, elevated plus maze test and forced swimming test. Following both, a single and double-hemorrhagic models of SAH, rats were found to have significant behavioral abnormalities on the open field test, sucrose preference test, elevated plus maze test, and forced swimming test. A more prominent disability was found in rats that underwent the double-hemorrhagic model of SAH than rats that underwent the single-hemorrhagic model. Both a single and double injection model of rats SAH are associated with significant behavioral disturbances including locomotor abnormalities, depressive behavior and increased anxiety, even as early as 3 weeks after SAH.

Cell-free DNA as a potential marker to predict carbon tetrachloride-induced acute liver injury in rats.

PURPOSE: Finding an optimal biomarker for the noninvasive evaluation of acute liver injury (ALI) may be of great value in predicting clinical outcomes and investigating potential treatments. We investigated cell-free DNA (CFD) as a potential biomarker to predict carbon tetrachloride-induced ALI in rats. METHODS: Forty-five Sprague-Dawley rats were randomly assigned to three groups. ALI was induced by carbon tetrachloride via a nasogastric tube at 1, 2.5, or 5 ml/kg of a 50 % solution. Fifteen additional rats underwent a sham procedure. Blood samples were drawn at time t which was 0 (baseline), 3, 6, 12, 24, 48, 72, 96, and 120 h for the measurements of CFD, glutamate-pyruvate transaminase (GPT), glutamate-oxaloacetate transaminase (GOT), and total bilirubin. Prothrombin time and histology were examined at 24 and 120 h following injection of 5 ml/kg carbon tetrachloride in 18 additional rats and in 10 control rats. RESULTS: CFD levels in rats subjected to carbon tetrachloride-induced ALI were significantly increased in all blood samples starting at 12 h after the induction of ALI (p < 0.001), reaching peak levels at 24 h. Blood GOT, GPT, and total bilirubin were elevated in all blood samples starting at 3 h after the induction of ALI (p < 0.0001), reaching peak levels by 48 h. A positive correlation was demonstrated between CFD levels and GOT (R (2) = 0.92), GPT (R (2) = 0.92), and total bilirubin (R (2) = 0.76). CFD levels correlated with liver damage seen on histological examination, as well as predicted liver damage, at 24 h after ALI. CONCLUSIONS: CFD may be a useful biomarker for the prediction and measurement of ALI. There is no evidence to suggest that CFD is superior to other available noninvasive biomarkers.

Combined therapeutic hypothermia and barbiturate coma reduces interleukin-6 in the cerebrospinal fluid after aneurysmal subarachnoid hemorrhage.

Inflammatory response with cytokine release is reported to correlate with clinical outcome after aneurysmal subarachnoid hemorrhage (SAH). In selected cases, hypothermia and barbiturate coma are applied as means for neuroprotection after severe SAH. Hypothermia and high-dose barbiturate are reported to attenuate the inflammatory response. In this pilot study, we assessed the effect of the combined therapy on the inflammatory response. In 15 patients with SAH, daily cerebrospinal fluid (CSF) and plasma samples were collected. Interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), IL-1beta, systemic leukocyte, and leukocyte counts in the CSF were quantified. Group 1 represented 7 cases treated with combined therapeutic hypothermia (33 degrees C) and barbiturate coma. Group 2 represented 8 cases without combined therapy. Compared with the systemic levels, all cases showed higher cytokine levels in the CSF. Mean IL-6 level in the CSF was significantly lower in group 1 (P<0.001). The ratio between IL-6 levels in the CSF and plasma, as a parameter for intrathecal synthesis, was significantly lower in group 1 (P=0.014). Mean CSF and systemic levels of TNF-alpha of group 1 were significantly higher compared with group 2 (P=0.009 and P<0.001). The mean systemic IL-1beta level was significantly lower in group 1 (P<0.001), as well as the leukocyte counts, both, systemic and in the CSF (P<0.001 and P=0.032). The present data show a most pronounced decrease of IL-6 levels in the CSF, beside decrease in systemic IL-1beta levels, systemic leukocyte counts, and CSF leukocyte counts in group 1, which would be expected to reflect an attenuation of inflammatory response. The impact and role of TNF-alpha remains unclear.