Niemann-Pick type C (NP-C) is a rare neurodegenerative disorder. Management is mainly supportive and symptomatic. The investigational use of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) showed a promising role in treating NP-C, although efficacy and safety have not been established. We conducted searches of MEDLINE, Cochrane, EMBASE, and other databases of reported cases of HP-β-CD compassionate use in NP-C disease. Sixteen reported cases were eligible, including evaluable information of 17 patients. The median onset age of HP-β-CD was 14 years (range 2-49 years). Intrathecal route was employed in 16 patients, in 3 patients simultaneously to IV infusions. Intracerebroventricular route was used in two patients. An objective improvement of clinical outcomes was measured in 14 patients, mainly by the NIH NP-C Clinical Severity Score and brainstem auditory evoked potential. Besides, an increase in metabolism and activities of the brain were observed in image tests and cholesterol biomarkers. Most patients showed some clinical benefit or a stabilization of NP-C progression. There were 17 adverse events (AEs) reported in 11 patients, 11 of them related to the drug and 6 to the route of administration. Loss of hearing was reported in four patients. The most severe AE were fever and chemical meningitis. Results suggest that efficacy may be partial and dependent on the early administration of the drug, the severity of the disease, and interpersonal variability. HP-β-CD could help stabilize NP-C with low toxicity potential, although some AEs have been reported. Moreover, controlled clinical trials would be necessary to evaluate the role of HP-β-CD in NP-C.

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Niemann-Pick disease type C (NPD-C) is a rare neurodegenerative disorder characterized by a lysosomal storage disorder. Treatment has been supportive and symptomatic. In animal studies, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) showed a significant decrease in cerebellar damage, neurological progression, and higher lifespan. Based on these results, HP-β-CD has been tested in NPD-C patients for last 8 years. The first compassionate uses of intravenous HP-β-CD obtained a limited improvement in neurological symptoms, probably associated to the non-permeation of the blood-brain barrier. The change or combination with intrathecal administrations of HP-β-CD achieved higher benefits, especially improvement or stabilization of NPD-C progression. Biomarkers of neurological cholesterol homeostasis are being investigated in order to quantify the response of HP-β-CD treatment. The results of a clinical trial recently published have reproduced the slowing of NPD-C progression in 14 patients treated with a dose-escalation protocol of HP-β-CD intrathecal monthly infusions, with respect to a historical comparison cohort. The safety profile of this therapy is acceptable, being the loss of hearing as the most frequent adverse event. However, some severe toxicities have been reported in relation with HP-β-CD, including chemical meningitis and fever. The short experience with HP-β-CD suggested that it could be effective in the management of NPD-C.

Haemodialysis reduces serum levetiracetam concentration and can lead to subtherapeutic levels. Close monitoring is necessary when dialysis is used on patients receiving anticonvulsant drugs that are extensively eliminated by the procedure.

What is known and objective Guidelines for prevention and treatment of peritonitis in paediatric patients recommend vancomycin. We present the clinical practice in neonates during peritoneal dialysis and evaluate dosage and serum levels of vancomycin. Case summary This case report describes a newborn with acute renal failure under continuous peritoneal dialysis therapy and intraperitoneal vancomycin. We report the treatment dosage and serum vancomycin levels. What is new and conclusion There is great variability in the recommended dose of vancomycin for continuous peritoneal dialysis and the available clinical experience. Further investigation of dosing in children particularly in newborns, especially in loading dose, is necessary.