Neurotoxicity is a term used to describe neurophysiological changes caused by exposure to toxic agents. Such exposure can result in neurocognitive symptoms and/or psychiatric disturbances. Common toxic agents include heavy metals, drugs, organophosphates, bacterial, and animal neurotoxins. Among heavy metal exposures, lead exposure is one of the most common exposures that can lead to significant neuropsychological and functional decline in humans. In this review, neurotoxic lead exposure's pathophysiology, etiology, and epidemiology are explored. In addition, commonly associated neuropsychological difficulties in intelligence, memory, executive functioning, attention, processing speed, language, visuospatial skills, motor skills, and affect/mood are explored.

Parkinson's disease (PD) is a common, degenerative disorder of the central nervous system. Individuals experience predominantly extrapyramidal symptoms including resting tremor, rigidity, bradykinesia, gait abnormalities, cognitive impairment, depression, and neurobehavioral concerns. Cognitive impairments associated with PD are diverse, including difficulty with attention, processing speed, executive functioning, memory recall, visuospatial functions, word-retrieval, and naming. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is FDA approved and has been shown to be effective in reducing motor symptoms of PD. Studies have found that stimulating STN and GPi are equally effective at improving motor symptoms and dyskinesias; however, there has been discrepancy as to whether the cognitive, behavioral, and mood symptoms are affected differently between the two targets. The present study used random-effects meta-analytic models along with a novel p-curve analytic procedure to compare the potential cognitive and emotional impairments associated with STN-DBS in the current literature to those associated with GPi-DBS. Forty-one articles were reviewed with an aggregated sample size of 1622 patients. Following STN-DBS, small declines were found in psychomotor speed, memory, attention, executive functions, and overall cognition; and moderate declines were found in both semantic and phonemic fluency. However, GPi-DBS resulted in fewer neurocognitive declines than STN-DBS (small declines in attention and small-moderate declines in verbal fluency). With regards to its effect on depression symptomatology, both GPi-DBS and STN-DBS resulted in lower levels of depressive symptoms post-surgery. From a neurocognitive standpoint, both GPi-DBS and STN-DBS produce subtle cognitive declines but appears to be relatively well tolerated.

OBJECTIVE There is an unmet need for safe and rapidly effective therapies for refractory brain radiation necrosis (RN). The aim of this prospective single-arm phase II trial was to evaluate the safety and efficacy of a single low-dose targeted bevacizumab infusion after blood-brain barrier disruption (BBBD) in adult patients with steroid-refractory brain RN. METHODS Ten adults with steroid-refractory, imaging-confirmed brain RN were enrolled between November 2016 and January 2018 and followed for 12 months after treatment. Bevacizumab 2.5 mg/kg was administered as a one-time targeted intra-arterial infusion immediately after BBBD. Primary outcomes included safety and > 25% decrease in lesion volume. Images were analyzed by a board-certified neuroradiologist blinded to pretrial diagnosis and treatment status. Secondary outcomes included changes in headache, steroid use, and functional status and absence of neurocognitive sequelae. Comparisons were analyzed using the Fisher exact test, Mann-Whitney U-test, linear mixed models, Wilcoxon signed-rank test, and repeated-measures 1-way ANOVA. RESULTS Ten adults (mean ± SD [range] age 35 ± 15 [22–62] years) participated in this study. No patients died or exhibited serious adverse effects of systemic bevacizumab. At 3 months, 80% (95% CI 44%–98%) and 90% (95% CI 56%–100%) of patients demonstrated > 25% decrease in RN and vasogenic edema volume, respectively. At 12 months, RN volume decreased by 74% (median [range] 76% [53%–96%], p = 0.012), edema volume decreased by 50% (median [range] 70% [−11% to 83%], p = 0.086), and headache decreased by 84% (median [range] 92% [58%–100%], p = 0.022) among the 8 patients without RN recurrence. Only 1 (10%) patient was steroid dependent at the end of the trial. Scores on 12 of 16 (75%) neurocognitive indices increased, thereby supporting a pattern of cerebral white matter recovery. Two (20%) patients exhibited RN recurrence that required further treatment at 10 and 11 months, respectively, after bevacizumab infusion. CONCLUSIONS For the first time, to the authors’ knowledge, the authors demonstrated that a single low-dose targeted bevacizumab infusion resulted in durable clinical and imaging improvements in 80% of patients at 12 months after treatment without adverse events attributed to bevacizumab alone. These findings highlight that targeted bevacizumab may be an efficient one-time treatment for adults with brain RN. Further confirmation with a randomized controlled trial is needed to compare the intra-arterial approach with the conventional multicycle intravenous regimen. Clinical trial registration no.: NCT02819479 (ClinicalTrials.gov)

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