Intraputamenal cerebral dopamine neurotrophic factor in Parkinson's disease: a randomized, double‐blind, multicenter phase 1 trial

Background: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD). Objective: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity. Methods: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone‐anchored transcutaneous port connected to four catheters. This phase 1 trial was divided into a placebo‐controlled, double‐blind, 6‐month main study followed by an active‐treatment 6‐month extension. Eligible patients, aged 35 to 75 years, had moderate idiopathic PD for 5 to 15 years and Hoehn and Yahr score ≤ 3 (off state). Seventeen patients were randomized to placebo (n = 6), 0.4 mg CDNF (n = 6), or 1.2 mg CDNF (n = 5). The primary endpoints were safety and tolerability of CDNF and DDS and catheter implantation accuracy. Secondary endpoints were measures of PD symptoms, including Unified Parkinson's Disease Rating Scale, and DDS patency and port stability. Exploratory endpoints included motor symptom assessment (PKG, Global Kinetics Pty Ltd, Melbourne, Australia) and positron emission tomography using dopamine transporter radioligand [18F]FE‐PE2I. Results: Drug‐related adverse events were mild to moderate with no difference between placebo and treatment groups. No severe adverse events were associated with the drug, and device delivery accuracy met specification. The severe adverse events recorded were associated with the infusion procedure and did not reoccur after procedural modification. There were no significant changes between placebo and CDNF treatment groups in secondary endpoints between baseline and the end of the main and extension studies. Conclusions: Intraputamenally administered CDNF was safe and well tolerated, and possible signs of biological response to the drug were observed in individual patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Ganglioglioma surgery associated with postoperative status epilepticus : a case report

Background: Gangliogliomas are brain tumors associated with drug-resistant focal epilepsy. In most cases, seizures improve after surgical treatment. It is still not concluded to what extent the lesion itself or the perilesional area contributes to the epileptogenicity. Case presentation: In the case presented in this report, the patient, a 24-year-old Caucasian male, developed a refractory status epilepticus after a surgical attempt to remove a cerebral ganglioglioma. The postoperative magnetic resonance imaging revealed that the lesion was intact, and that inadvertently only the perilesional area and adjacent cortex had been resected. The patient underwent a new surgical procedure where the ganglioglioma was removed, and the status epilepticus cessated. Conclusions: This clinical case suggests that the lesion itself plays an important role in seizure generation and propagation, and notably, that the surrounding cortex by an inhibitory action can act as a gate to seizure spread

Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease : A Randomized, Double-Blind, Multicenter Phase 1 Trial

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