Intracerebroventricular Delivery as a Safe, Long-Term Route of Drug Administration

Intrathecal delivery methods have been used for many decades to treat a broad range of central nervous system disorders. A literature review demonstrated that intracerebroventricular route is an established and well-tolerated method for prolonged central nervous system drug delivery in pediatric and adult populations. Intracerebroventricular devices were present in patients from one to 7156 days. The number of punctures per device ranged from 2 to 280. Noninfectious complication rates per patient (range, 1.0% to 33.0%) were similar to infectious complication rates (0.0% to 27.0%). Clinician experience and training and the use of strict aseptic techniques have been shown to reduce the frequency of complications.(VLID)485637

Best practices for the use of intracerebroventricular drug delivery devices

For decades, intracerebroventricular (ICV), or intraventricular, devices have been used in the treatment of a broad range of pediatric and adult central nervous system (CNS) disorders. Due to the limited permeability of the blood brain barrier, diseases with CNS involvement may require direct administration of drugs into the brain to achieve full therapeutic effect. A recent comprehensive literature review on the clinical use and complications of ICV drug delivery revealed that device-associated complication rates are variable, and may be as high as 33% for non-infectious complications and 27% for infectious complications. The variability in reported safety outcomes may be driven by a lack of consensus on best practices of device use. Numerous studies have demonstrated that employing strict aseptic techniques and following stringent protocols can dramatically reduce complications. Key practices to be considered in facilitating the safe, long-term use of these devices are presented.(VLID)469777

Cerliponase Alfa for the Treatment of Atypical Phenotypes of CLN2 Disease: A Retrospective Case Series.

BackgroundThe classic phenotype of CLN2 disease (neuronal ceroid lipofuscinosis type 2) typically manifests between ages 2 and 4 years with a predictable clinical course marked by epilepsy, language developmental delay, and rapid psychomotor decline. Atypical phenotypes exhibit variable time of onset, symptomatology, and/or progression. Intracerebroventricular-administered cerliponase alfa (rhTPP1 enzyme) has been shown to stabilize motor and language function loss in patients with classic CLN2 disease, but its impact on individuals with atypical phenotypes has not been described.MethodsA chart review was conducted of 14 patients (8 male, 6 female) with atypical CLN2 phenotypes who received cerliponase alfa. Pre- and posttreatment CLN2 Clinical Rating Scale Motor and Language (ML) domain scores were compared.ResultsMedian age at first presenting symptom was 5.9 years. First reported symptoms were language abnormalities (6 [43%] patients), seizures (4 [29%]), ataxia/language abnormalities (3 [21%]), and ataxia alone (1 [7%]). Median age at diagnosis was 10.8 years. ML score declined before treatment in 13 (93%) patients. Median age at treatment initiation was 11.7 years; treatment duration ranged from 11 to 58 months. From treatment start, ML score remained stable in 11 patients (treatment duration 11-43 months), improved 1 point in 1 patient after 13 months, and declined 1 point in 2 patients after 15 and 58 months, respectively. There were 13 device-related infections in 8 patients (57%) and 10 hypersensitivity reactions in 6 (43%).ConclusionsCerliponase alfa is well tolerated and has the potential to stabilize motor and language function in patients with atypical phenotypes of CLN2 disease

Cerliponase Alfa for the Treatment of Atypical Phenotypes of CLN2 Disease: A Retrospective Case Series.

BackgroundThe classic phenotype of CLN2 disease (neuronal ceroid lipofuscinosis type 2) typically manifests between ages 2 and 4 years with a predictable clinical course marked by epilepsy, language developmental delay, and rapid psychomotor decline. Atypical phenotypes exhibit variable time of onset, symptomatology, and/or progression. Intracerebroventricular-administered cerliponase alfa (rhTPP1 enzyme) has been shown to stabilize motor and language function loss in patients with classic CLN2 disease, but its impact on individuals with atypical phenotypes has not been described.MethodsA chart review was conducted of 14 patients (8 male, 6 female) with atypical CLN2 phenotypes who received cerliponase alfa. Pre- and posttreatment CLN2 Clinical Rating Scale Motor and Language (ML) domain scores were compared.ResultsMedian age at first presenting symptom was 5.9 years. First reported symptoms were language abnormalities (6 [43%] patients), seizures (4 [29%]), ataxia/language abnormalities (3 [21%]), and ataxia alone (1 [7%]). Median age at diagnosis was 10.8 years. ML score declined before treatment in 13 (93%) patients. Median age at treatment initiation was 11.7 years; treatment duration ranged from 11 to 58 months. From treatment start, ML score remained stable in 11 patients (treatment duration 11-43 months), improved 1 point in 1 patient after 13 months, and declined 1 point in 2 patients after 15 and 58 months, respectively. There were 13 device-related infections in 8 patients (57%) and 10 hypersensitivity reactions in 6 (43%).ConclusionsCerliponase alfa is well tolerated and has the potential to stabilize motor and language function in patients with atypical phenotypes of CLN2 disease