Claudia L. Craven, Paul Gissen, Rebecca Bower, Laura Lee, Kristian Aquilina, and Dominic N. P. Thompson
Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare autosomal recessive disease caused by tripeptidyl peptidase 1 enzyme deficiency. At the authors’ center, the medication cerliponase alfa is administered every 2 weeks via the intracerebroventricular (ICV) route. This requires the placement of a ventricular access device (VAD) or reservoir and frequent percutaneous punctures of this device over the child’s lifetime. In this study, the authors audited the longevity and survival of these VADs and examined the causes of device failure.
A single-center survival analysis of VAD insertions and revisions (January 2014 through June 2020) was conducted. All children received cerliponase alfa infusions through a VAD. Patient characteristics and complications were determined from a prospectively maintained surgical database and patient records. For the VAD survival analysis, the defined endpoint was when the device was removed or changed. Reservoir survival was assessed using Kaplan-Meier curves and the log-rank (Cox-Mantel) test.
A total of 17 patients had VADs inserted for drug delivery; median (range) age at first surgery was 4 years 4 months (1 year 8 months to 15 years). Twenty-six VAD operations (17 primary insertions and 9 revisions) were required among these 17 patients. Twelve VAD operations had an associated complication, including CSF infection (n = 6) with Propionibacterium and Staphylococcus species being the most prevalent organisms, significant surgical site swelling preventing infusion (n = 3), leakage/wound breakdown (n = 2), and catheter obstruction (n = 1). There were no complications or deaths associated with VAD insertion. The median (interquartile range) number of punctures was 59.5 (7.5–82.0) for unrevised VADs (n = 17) versus 2 (6–87.5) for revised VADs (n = 9) (p = 0.70). The median survival was 301 days for revisional reservoirs (n = 9) versus 2317 days for primary inserted reservoirs (n = 17) (p = 0.019).
In the context of the current interest in intrathecal drug delivery for rare metabolic disorders, the need for VADs is likely to increase. Auditing the medium- to long-term outcomes associated with these devices will hopefully result in their wider application and may have potential implications on the development of new VAD technologies. These results could also be used to counsel parents prior to commencement of therapy and VAD implantation.
Michael F. Barbaro, Kelsi Chesney, Daniel R. Kramer, Spencer Kellis, Terrance Peng, Zack Blumenfeld, Angad S. Gogia, Morgan B. Lee, Janet Greenwood, George Nune, Laura A. Kalayjian, Christianne N. Heck, Charles Y. Liu, and Brian Lee
Closed-loop brain-responsive neurostimulation via the RNS System is a treatment option for adults with medically refractory focal epilepsy. Using a novel technique, 2 RNS Systems (2 neurostimulators and 4 leads) were successfully implanted in a single patient with bilateral parietal epileptogenic zones. In patients with multiple epileptogenic zones, this technique allows for additional treatment options. Implantation can be done successfully, without telemetry interference, using proper surgical planning and neurostimulator positioning.
Trajectories for the depth leads were planned using neuronavigation with CT and MR imaging. Stereotactic frames were used for coordinate targeting. Each neurostimulator was positioned with maximal spacing to avoid telemetry interference while minimizing patient discomfort. A separate J-shaped incision was used for each neurostimulator to allow for compartmentalization in case of infection. In order to minimize surgical time and risk of infection, the neurostimulators were implanted in 2 separate surgeries, approximately 3 weeks apart.
The neurostimulators and leads were successfully implanted without adverse surgical outcomes. The patient recovered uneventfully, and the early therapy settings over several months resulted in preliminary decreases in aura and seizure frequency. Stimulation by one of the neurostimulators did not result in stimulation artifacts detected by the contralateral neurostimulator.
Christine Park, Lefko T. Charalambous, Zidanyue Yang, Syed M. Adil, Sarah E. Hodges, Hui-Jie Lee, Laura Zitella Verbick, Aaron R. McCabe, and Shivanand P. Lad
Nontraumatic, primary intracerebral hemorrhage (ICH) accounts for 2 million strokes worldwide annually and has a 1-year survival rate of 50%. Recent studies examining functional outcomes from ICH evacuation have been performed, but limited work has been done quantifying the incidence of subsequent complications and their healthcare economic impact. The purpose of this study was to quantify the incidence and healthcare resource utilization (HCRU) for major complications that can arise from ICH.
The IBM MarketScan Research databases were used to retrospectively identify patients with ICH from 2010 to 2015. Complications examined included cerebral edema, hydrocephalus, venous thromboembolic events (VTEs), pneumonia, urinary tract infections (UTIs), and seizures. For each complication, inpatient mortality and HCRU were assessed.
Of 25,322 adult patients included, 10,619 (42%) developed complications during the initial admission of ICH: 22% had cerebral edema, 11% hydrocephalus, 10% pneumonia, 6% UTIs, 5% seizures, and 5% VTEs. The inpatient mortality rates at 7 and 30 days for each complication of ICH ranked from highest to lowest were hydrocephalus (24% and 32%), cerebral edema (15% and 20%), pneumonia (8% and 18%), seizure (7% and 13%), VTE (4% and 11%), and UTI (4% and 8%). Hydrocephalus had the highest total cost (median $92,776, IQR $39,308–$180,716) at 7 days post–ICH diagnosis and the highest cumulative total cost (median $170,839, IQR $91,462–$330,673) at 1 year post–ICH diagnosis.
This study characterizes one of the largest cohorts of patients with nontraumatic ICH in the US. More than 42% of the patients with ICH developed complications during initial admission, which resulted in high inpatient mortality and considerable HCRU.
Marlon G. Saria, Courtney Corle, Jethro Hu, Jeremy D. Rudnick, Surasak Phuphanich, Maciej M. Mrugala, Laura K. Crew, Daniela A. Bota, Beverly Dan Fu, Ryan Y. Kim, Tiffany Brown, Homira Feely, Joanne Brechlin, Bradley D. Brown, Jan Drappatz, Patrick Y. Wen, Clark C. Chen, Bob Carter, Jong Woo Lee, and Santosh Kesari
The object of this study was to determine the tolerability and activity of lacosamide in patients with brain tumors.
The authors reviewed the medical records at 5 US academic medical centers with tertiary brain tumor programs, seeking all patients in whom a primary brain tumor had been diagnosed and who were taking lacosamide.
The authors identified 70 patients with primary brain tumors and reviewed seizure frequency and toxicities. The majority of the patients had gliomas (96%). Fifty-five (78%) had partial seizures only, and 12 (17%) had generalized seizures. Most of the patients (74%) were started on lacosamide because of recurrent seizures. Forty-six patients (66%) reported a decrease in seizure frequency, and 21 patients (30%) reported stable seizures. Most of the patients (54 [77%]) placed on lacosamide did not report any toxicities.
This retrospective analysis demonstrated that lacosamide was both well tolerated and active as an add-on antiepileptic drug (AED) in patients with brain tumors. Lacosamide's novel mechanism of action will allow for concurrent use with other AEDs, as documented by its activity across many different types of AEDs used in this patient population. Larger prospective studies are warranted.