Background: We evaluated the effects of low doses of the tyrosine kinase Abelson (Abl) inhibitor Nilotinib, on safety and pharmacokinetics in Parkinson’s disease dementia or dementia with Lewy bodies.Objectives: The primary outcomes of this study were safety and tolerability; pharmacokinetics and target engagement were secondary, while clinical outcomes were exploratory.Methods: Twelve subjects were randomized into 150 mg (n = 5) or 300 mg (n = 7) groups and received Nilotinib orally every day for 24 weeks.Results: This study shows that 150 mg and 300 mg doses of Nilotinib appear to be safe and tolerated in subjects with advanced Parkinson’s disease. Nilotinib is detectable in the cerebrospinal fluid (CSF) and seems to engage the target Abl. Motor and cognitive outcomes suggest a possible beneficial effect on clinical outcomes. The CSF levels of homovanillic acid are significantly increased between baseline and 24 weeks of treatment. Exploratory CSF biomarkers were measured.Conclusions: This small proof-of-concept study lacks a placebo group and participants were not homogenous, resulting in baseline differences between and within groups. This limits the interpretations of the biomarker and clinical data, and any conclusions should be drawn cautiously. Nonetheless, the collective observations suggest that it is warranted to evaluate the safety and efficacy of Nilotinib in larger randomized, double-blind, placebo-controlled trials.

Patients with Alzheimer's disease (AD) and patients with semantic dementia (SD) both exhibit deficits on explicit tasks of semantic memory such as picture naming and category fluency. These deficits have been attributed to a degradation of the stored semantic network. An alternative explanation attributes the semantic deficit in AD to an impaired ability to consciously retrieve items from the semantic network. The present study used an implicit lexical-decision priming task to examine the integrity of the underlying semantic network in AD and SD patients matched for degree of impairment on explicit semantic memory tasks. The AD (n=11) and SD (n=11) patient groups were matched for age, education, level of dementia and impairment on four explicit semantic memory tasks. Healthy elderly participants (n=22) were matched for age and education. Semantic priming effects were evaluated for three types of semantic relationships (attributes, category coordinates, and category superordinates) and compared to lexical associative priming. Healthy controls showed significant priming across all conditions. In contrast, AD patients showed normal superordinate priming, and significant (although somewhat reduced) coordinate priming, but no attribute priming. SD patients showed no priming effect for any semantic relationship. All groups showed significant associative priming. The results indicate that SD patients do indeed have substantial degradation of semantic memory, while AD patients have a partially intact network, accounting for priming in superordinate and coordinate conditions. These findings suggest that AD patients' impairment on explicit semantic tasks is the product of deficient explicit retrieval in combination with a partially degraded semantic network.

This index case report describes a novel programming approach that utilizes the 8-contact directional Deep Brain Stimulation (DBS) lead to effectively control the akinesia, rigidity and tremor of Parkinson's Disease (PD), as well as a severe kinetic tremor of Essential Tremor (ET), in a patient with overlapping symptoms of both PD and ET. Through utilizing a bipolar directional montage on a single segmented contact, symptom control was attained via likely co-activation of the Subthalamic Nucleus (STN) and the adjacent Zona Incerta (ZI). The patient is a 67-year-old professional guitarist with a long-standing diagnosis of ET manifesting with bilateral kinetic tremor, who then developed right lateralizing symptoms indicative of PD. After optimal medical management did not confer sufficient control, he underwent left-sided unilateral DBS targeting the STN. Both intraoperatively and post-operatively, omnidirectional, and directional electrode review resulted in significant akinesia, rigidity, and as well as resting tremor control but failed to sufficiently improve the kinetic tremor. As electrode 2B was shown to be the most efficacious with the largest therapeutic window, a bipolar directional montage on a single segmented contact was tried with the idea of possibly further extending the axial asymmetry of the directional stimulation toward the adjacent ZI to impact the kinetic tremor. This montage resulted in full kinetic and resting tremor control as well as akinesia and rigidity response [2B cathode (–), 2A anode (+), 2C anode (+) (1.4 mA, rate 160 Hz, pulse width 60 μs)]. At 6 months post initial programming, no montage changes have been made, and the patient has experienced a reduction in Motor UPDRS scores from 23 to 3 (evaluated off medication), full resolution of kinetic tremor and normalization of handwriting, as well as significant reduction in his medication requirements. This patient's response to a single segment bipolar directional montage, and lack of response from monopolar directional stimulation in the same area, does suggest the possibility of further axial asymmetric tissue activation and thus co-activation of both the dorsal STN and adjacent ZI. Further modeling and study are warranted.

While deep brain stimulation (DBS) is now standard therapy for the treatment of Parkinson's disease, essential tremor, and dystonia, infections remain one of the most common perioperative complications. In this report, we describe a 58-year-old female with a history of medically refractory Parkinson's disease, who underwent magnetic resonance (MR)-guided bilateral subthalamic DBS. While the initial surgery and programming were successful, she returned in follow-up with signs of a generator pocket infection. She was taken to surgery for hardware explantation, and cultures revealed multispecies growth which included the rare Cupriavidus pauculus species. This is the first report of C. pauculus infection in conjunction with a neuromodulation device. We provide a literature review and discussion of C. pauculus, and its implications in the context of DBS surgery.