Noninvasive Calculation of Cerebrospinal Fluid Production Using Phase-Contrast Magnetic Resonance Imaging: First Implementation in Augusta, Georgia.

This retrospective review examines the utility of phase-contrast magnetic resonance imaging (PC-MRI) to calculate flow through the aqueduct between the third and fourth ventricles to estimate cerebrospinal fluid (CSF) production. Imaging software quantified the CSF flow rate across the aqueduct of four females and two males at a single center, and the mean of these results was compared to the established mean CSF production calculated by invasive techniques. There was no significant difference between the means, contributing to the body of literature suggesting the utility of PC-MRI in estimating CSF production rates.

The intercostal nerve as a target for diagnostic biopsy.

OBJECTIVE Peripheral nerve biopsy is a useful tool in diagnosing peripheral neuropathies. Sural and gracilis nerves have become the most common targets for nerve biopsy. However, the yield of sural nerve biopsy is limited in patients who have motor neuropathies, and gracilis nerve biopsy presents technical challenges and increased complications. The authors propose the intercostal nerve as an alternative motor nerve target for biopsy. METHODS A total of 4 patients with suspected peripheral neuropathies underwent intercostal nerve biopsy at the authors' institution. A rib interspace that is inferior to the pectoralis muscle and anterior to the anterior axillary line is selected for the procedure. Generally the lower intercostal nerves (i.e., T7-11) are targeted. An incision is made over the inferior aspect of the superior rib at the chosen interspace. Blunt dissection is carried down to the neurovascular bundle and the nerve is isolated, ligated, and cut to send for pathological examination. RESULTS The average operative time for all cases was 73 minutes, with average blood loss of 8 ml. Biopsy results from 1 patient exhibited axonopathy, and the other 3 patients demonstrated axonopathy with demyelination. There were no short- or long-term postoperative complications. None of the patients reported sensory or motor deficits related to the biopsy at 6 weeks postoperatively. CONCLUSIONS The intercostal nerve can be an alternative target for biopsy, especially in patients with predominantly motor neuropathies, due to its mixed sensory and motor fibers, straightforward anatomy, minimal risk of serious sensory deficits, and no risk of motor impairment.

Significant anti-tumor effect of bevacizumab in treatment of pineal gland glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most aggressive subtype of malignant gliomas. Current standard treatment for GBM involves a combination of cytoreduction through surgical resection, followed by radiation with concomitant and adjuvant chemotherapy (temozolomide). The role of bevacizumab in the treatment of GBM continues to be a topic of ongoing research and debate. Despite aggressive treatment, these tumors remain undoubtedly fatal, especially in the elderly. Furthermore, tumors present in the pineal gland are extremely rare, accounting for only 0.1-0.4 % of all adult brain tumors, with this location adding to the complexity of treatment. We present a case of GBM, at the rare location of pineal gland, in an elderly patient who was refractory to initial standard of care treatment with radiation and concomitant and adjuvant temozolomide, but who developed a significant response to anti-angiogenic therapy using bevacizumab.

Intracranial calcified pseudocyst reaction to a shunt catheter.

A 9-year-old boy with spina bifida, Chiari II malformation, and hydrocephalus presented with signs of increased intracranial pressure consistent with a shunt malfunction. Radiological investigations revealed an intracranial calcified lesion along the ventricular catheter. A shunt tap revealed a translucent milky white fluid. The patient underwent a ventriculostomy and, eventually, a shunt revision. Pathology findings were consistent with the formation of dystrophic calcification and a pseudocyst around the shunt catheter. Postoperatively, the patient returned to his neurological baseline. This is, to the best of the authors' knowledge, the first report of an intracranial calcified pseudocyst in a patient with normal renal function.

Indium 111 diethylenetriamine pentaacetic acid scintigraphy in the identification and management of intrathecal pump malfunction.

BACKGROUND: Intrathecal drug-delivery systems have become widely used tools in the management of refractory chronic pain and spasticity. Because increasing numbers of patients are using these systems, rehabilitation specialists frequently are the initial care providers who identify clinical signs and symptoms indicating possible complications relating to the implanted system. Identification of a pump malfunction often presents a diagnostic challenge. Distinguishing among progression of disease, new organic problems, and/or drug-device complications is critical. The use of nuclear medicine indium 111 diethylenetriamine pentaacetic acid (DTPA) studies represents a highly effective, straightforward, minimally invasive way to assess implant function and drug distribution. OBJECTIVE: To identify patients with suspected intrathecal pump malfunction and to determine whether the use of indium 111 DTPA is effective in identifying the source of failure. DESIGN: A retrospective review was performed from 2011 to 2012. SETTING: The study was performed at Georgia Health Sciences University. PATIENTS: The 23 selected patients had implanted devices for either spasticity or pain and were experiencing symptoms of a possible pump malfunction despite normal radiographic imaging. Twenty-four scintigraphic studies were performed, with malfunction documented in 19 patients. METHODS: A standard refill technique was used to inject 0.3 mL of indium 111 DTPA into the pump reservoir. Radionuclide images were reviewed at varying time points up to 48 hours after injection. The extent of radionuclide progression from the pump reservoir to the intrathecal space was evaluated. In cases in which a problem with the implant was identified, correlation with operative findings is described. RESULTS: Normal results of studies ultimately correlated with other clinical issues and confirmed an alternative etiology for the clinical changes noted. In studies with abnormal results, several patterns of failure were identified: restriction of the radionuclide to the pump reservoir, extravasations of tracer into the pump subcutaneous pocket, failure of the tracer to migrate from the subcutaneous catheter to the intrathecal space, and pooling of the tracer in the subcutaneous tissues. In all cases, surgical findings confirmed the suspected mechanism of malfunction as determined by the study. CONCLUSIONS: Indium 111 DTPA scintigraphy is a safe, straightforward way to identify and characterize clinical changes associated with intrathecal drug-delivery systems and to guide appropriate and clinical surgical management.

Evaluation of salvage techniques for infected baclofen pumps in pediatric patients with cerebral palsy.

OBJECT: Intrathecal baclofen therapy has been used successfully for intractable spasticity in children with cerebral palsy. Infections are rare, but they are potentially life threatening if complicated by bacteremia or meningitis. Treatment without removal of the system is desirable if it can be done safely and effectively. METHODS: The Authors reviewed the records of 207 patients ranging from 3 to 18 years of age with cerebral palsy who underwent placement or revision of a baclofen pump. They identified 38 patients with suspected or documented infectious complications. Initial attempts were made to eradicate infection with the devices in situ in all patients. Methods and effectiveness of pump salvage were evaluated. RESULTS: Of the 38 patients identified, 13 (34.2%) had documented infections; 11 had deep wound/pocket empyemas and 2 had meningitis. Eight patients with deep wound infections received intravenous antibiotics alone. All required pump explantation. The remaining 3 patients underwent a washout procedure as well; the infection was cured in 1 patient. Both patients with meningitis received intravenous and intrathecal antibiotics, and both required device explantation. In addition, 25 patients (65.8%) had excessive or increasing wound erythema. No objective criteria to document a superficial infection were present. The wounds were considered suspicious and were managed with serial examinations and oral antibiotics. The erythema resolved in 24 of the 25 patients. CONCLUSIONS: In general, observation, wound care, and oral antibiotics are sufficient for wounds that are suspicious for superficial infection. For deep-seated infection, antibiotic therapy alone is generally insufficient and explantation is required. Washout procedures can be considered, but failures are common.

Treatment with transducible phosphopeptide analogues of the small heat shock-related protein, HSP20, after experimental subarachnoid hemorrhage: prevention and reversal of delayed decreases in cerebral perfusion.

OBJECT: Delayed vasospasm is a significant cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Proteomic therapeutics offers a new modality in which biologically active proteins or peptides are transduced into cells via covalent linkage to cell permeant peptides (CPPs). The hypothesis of this study was that either intrathecal or intravenous delivery of a phosphopeptide mimetic of the small heat shock-related protein, HSP20, linked to a CPP, would inhibit delayed decreases in cerebral perfusion after experimental SAH in a rat model. METHODS: This study was conducted in 3 parts: 1) prevention and 2) reversal of delayed decreases in cerebral perfusion via either intrathecal or intravenous administration of a CPP linked to phosphopeptide mimetics of HSP20 (AZX100) and 3) determining the effect of intravenous administration of AZX100 on blood pressure and heart rate. Subarachnoid hemorrhage was induced in rats by endovascular perforation. Subsequently, AZX100 was administered intrathecally via a cisternal catheter or intravenously. Cerebral perfusion was determined by laser Doppler monitoring. Blood pressure was monitored by telemetry in a separate group of naïve animals treated with AZX100 for 24 hours. RESULTS: The maximal decrease in cerebral perfusion occurred 3 days after SAH. Cisternal administration of AZX100 (0.14-0.57 mg/kg) 24 hours after hemorrhage prevented decreases in cerebral perfusion after SAH. Animals receiving lower doses of AZX100 (0.068 mg/kg) or a scrambled sequence of the active HSP20 peptide linked to CPP developed decreases in cerebral perfusion similar to those seen in control animals. Intravenous administration of AZX100 (1.22 mg/kg) 24 hours after hemorrhage prevented the decreases in cerebral perfusion seen in the controls. Intravenous administration (0.175 mg/kg and 1.22 mg/kg) of AZX100 on Days 2 and 3 after SAH reversed decreases in cerebral perfusion as early as Day 3. There was no impact of AZX100 on blood pressure or heart rate at doses up to 2.73 mg/kg. CONCLUSIONS: Cisternal administration of AZX100 24 hours after hemorrhage prevented decreases in cerebral perfusion. Intravenous administration of AZX100 also prevented and reversed decreases in cerebral perfusion at doses that did not induce hypotension. Transduction of biologically active motifs of downstream regulators like HSP20 represents a potential novel treatment for SAH.

Postoperative pain management after craniotomy: evaluation and cost analysis.

OBJECTIVE: Patients undergoing craniotomies have traditionally received opiates for the management of their postoperative pain. The use of narcotic pain medications can be costly, can decrease early walking, can lengthen hospital stay, and can alter a patient's neurological examination results. The use of alternative pain medications such as cyclooxygenase-2 (COX-2) inhibitors may benefit patients by resolving many of these issues. Compared with traditional nonsteroidal anti-inflammatory drugs, these anti-inflammatory medications may be used safely in neurosurgical patients because of their selective inhibition of the COX-2 enzyme, which avoids the platelet dysfunction caused by other nonsteroidal anti-inflammatory drugs. METHODS: A randomized, single-blinded prospective study was used to evaluate the efficacy of alternative pain management strategies for patients who have undergone craniotomy. Twenty-seven patients were randomly assigned to a control group (n = 13) receiving narcotics alone or an experimental group (n = 14) receiving a COX-2 inhibitor in addition to narcotic pain medications. RESULTS: The narcotics group was noted to have statistically significantly higher visual analog scale scores, increased length of stay, and increased narcotic use compared with the COX-2 group. The narcotics group also had increased hospitalization costs when compared with the COX-2 group. CONCLUSION: The use of scheduled atypical analgesics, such as COX-2 inhibitors, in addition to narcotics for the management of postoperative pain after craniotomy may provide better pain control, may decrease side effects associated with narcotic pain medications, may encourage earlier walking, and may reduce total hospitalization costs.

Evolution of the treatment of cerebral vasospasm.

Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is a disease process for which the lack of effective treatments has plagued neurosurgeons for decades. Historically, successful treatment after SAH in the acute setting was often followed by a rapid, uncontrollable deterioration in the subacute interval. Little was known regarding the nature and progression of this condition until the mid-1800s, when the disease was first described by Gull. Insight into the origin and natural history of cerebral vasospasm came slowly over the next 100 years, until the 1950s. Over the past five decades our understanding of cerebral vasospasm has expanded exponentially. This newly discovered information has been used by neurosurgeons worldwide for successful treatment of complications associated with vasospasm. Nevertheless, although great strides have been made toward elucidating the causes of cerebral vasospasm, a lasting cure continues to elude experts and the disease continues to wreak havoc on patients after aneurysmal SAH.

Heat shock protein expression in cerebral vessels after subarachnoid hemorrhage.

OBJECTIVE: The mechanisms of cerebral vasospasm after subarachnoid hemorrhage (SAH) remain controversial. Recent data have implicated two small heat shock proteins (HSPs), namely HSP20 and HSP27, in the regulation of vascular tone. Increases in the phosphorylation of HSP20 are associated with vasorelaxation, and increases in the phosphorylation of HSP27 are associated with impaired vasorelaxation. Therefore, we hypothesized that alterations in the expression and/or phosphorylation of these two small HSPs might play a role in cerebral vasospasm after SAH. METHODS: A rat model of endovascular perforation was used to induce SAH. Middle cerebral arteries were harvested from control animals, sham-treated animals, and animals with SAH, 48 hours after SAH induction. Dose-response curves for endothelium-independent (sodium nitroprusside, 10(-8) to 10(-4) mol/L) and endothelium-dependent (bradykinin, 10(-10) to 10(-5) mol/L) relaxing agents were recorded ex vivo. Physiological responses were correlated with the expression and phosphorylation of HSP20 and HSP27 by using one- and two-dimensional immunoblots. RESULTS: There was impaired endothelium-independent and endothelium-dependent relaxation in cerebral vessels after SAH. These changes were associated with decreased expression of both total and phosphorylated HSP20 and increases in the amount of phosphorylated HSP27. CONCLUSION: In this model, impaired relaxation of cerebral vessels after SAH was associated with increases in the amount of phosphorylated HSP27 and decreases in the expression and phosphorylation of HSP20. These data are consistent with alterations in the expression and phosphorylation of these small HSPs in other models of vasospasm.