BACKGROUND: Lesioning the Forel field or the subthalamic region is considered a possible treatment for tremoric patients with Parkinson disease, essential tremor, and other diseases. This surgical treatment was performed in the 1960s to 1970s and was an alternative to thalamotomy. Recently, there has been increasing interest in the reappraisal of stimulating and/or lesioning these targets, partly as a result of innovations in imaging and noninvasive ablative technologies, such as magnetic resonance-guided focused ultrasonography. OBJECTIVE: We wanted to perform a thorough review of the subthalamic region, both from an anatomic and a surgical standpoint, to offer a comprehensive and updated analysis of the techniques and results reported for patients with tremor treated with different techniques. METHODS: We performed a systematic review of the literature, gathering articles that included patients who underwent ablative or stimulation surgical techniques, targeting the pallidothalamic pathways (pallidothalamic tractotomy), cerebellothalamic pathway (cerebellothalamic tractotomy), or subthalamic area. RESULTS: Pallidothalamic tractotomy consists of a reduced area that includes pallidofugal pathways. It may be considered an interesting target, given the benefit/risk ratio and the clinical effect, which, compared with pallidotomy, involves a lower risk of injury or involvement of vital structures such as the internal capsule or optic tract. Cerebellothalamic tractotomy and/or posterior subthalamic area are other alternative targets to thalamic stimulation or ablative surgery. CONCLUSIONS: Based on the significant breakthrough that magnetic resonance-guided focused ultrasonography has meant in the neurosurgical world, some classic targets such as the pallidothalamic tract, Forel field, and posterior subthalamic area may be reconsidered as surgical alternatives for patients with movement disorders.

Background During magnetic resonance-guided focused ultrasound for essential or parkinsonian tremor, adverse events (headache, nausea/vomiting, or anxiety) may alter the outcome of the procedure despite being mostly transient and mild. Objectives Our aim was to analyze the relationship between demographic, procedural, and anesthetic characteristics with magnetic resonance/ultrasound-related events. Methods This was a retrospective study at the Clinica Universidad de Navarra of patients undergoing thalamotomy with magnetic resonance-guided focused ultrasound between September 2018 and October 2019. The anesthesia protocol included headache and nausea/vomiting prophylaxis and rescue therapy. Dexmedetomidine was used for anxiolysis in some patients after thorough multidisciplinary assessment. Results A total of 123 patients were included. Headache was directly related to skull density ratio (P < 0.001) and skull thickness (P = 0.02). Patients with a skull density ratio less than 0.48 had 3 times the odds of experiencing moderate or severe headache (odds ratio [OR], 3.08; 95% confidence interval [CI], 1.21-7.82) and had a higher odds of aborting sonication due to pain. Sex was associated with increased nausea (P = 0.007). Women had 4 times the odds of nausea than men (OR, 4.4; 95% CI, 1.61-12.11). Dexmedetomidine did not reduce headache or nausea incidence. Patients who received dexmedetomidine had a higher number (P = 0.01) and total minutes of sonication (P = 0.01). Conclusions Patients with lower skull density ratios and higher skull thicknesses could benefit from an aggressive analgesic prophylaxis. Women are more likely to experience nausea. Dexmedetomidine did not reduce headache and nausea, but increased the number and duration of sonications. Its exact effect on tremor is still unclear.

Aims To identify and prioritize the root causes of adverse drug events (ADEs) in hospitals and to assess the ability of artificial intelligence (AI) capabilities to prevent ADEs. Design A mixed method design was used. Methods A cross-sectional study for hospitals in Spain was carried out between February and April 2019 to identify and prioritize the root causes of ADEs. A nominal group technique was also used to assess the ability of AI capabilities to prevent ADEs. Results The main root cause of ADEs was a lack of adherence to safety protocols (64.8%), followed by identification errors (57.4%), and fragile and polymedicated patients (44.4%). An analysis of the AI capabilities to prevent the root causes of ADEs showed that identification and reading are two potentially useful capabilities. Conclusion Identification error is one of the main root causes of drug adverse events and AI capabilities could potentially prevent drug adverse events. Impact This study highlights the role of AI capabilities in safely identifying both patients and drugs, which is a crucial part of the medication administration process, and how this can prevent ADEs in hospitals.

We describe a Caucasian man in his late 60s who was admitted to the intensive care unit (ICU) with a history of cardiogenic shock secondary to an acute myocardial infarction. The patient's baseline serum creatinine levels were 0.9-1 mg/dL. On day 7 of the admission treatment with quetiapine was initiated due to a delirium episode. The next day the patient developed an erythematous-maculopapular rash and fever, with eosinophilia in the blood count. Over the following days the patient experienced an acute deterioration of kidney function requiring continuous renal replacement therapy. The skin lesions and eosinophilia resolved after withdrawal of quetiapine and systemic steroid therapy was administered. The patient was discharged from the ICU with a serum creatinine level of 2.6 mg/dL. Three months later, blood tests showed no recovery of the kidney function. According to the Naranjo adverse drug reaction probability scale, this event would be classified as 'probable' DRESS syndrome and, based on the RegiSCAR scoring system, was classified as 'definite' DRESS syndrome.

Background: Dexmedetomidine is frequently used for sedation during deep brain stimulator implantation in patients with Parkinson's disease, but its effect on subthalamic nucleus activity is not well known. The aim of this study was to quantify the effect of increasing doses of dexmedetomidine in this population. Methods: Controlled clinical trial assessing changes in subthalamic activity with increasing doses of dexmedetomidine (from 0.2 to 0.6 mg kg(-1) h(-1)) in a non-operating theatre setting. We recorded local field potentials in 12 patients with Parkinson's disease with bilateral deep brain stimulators (24 nuclei) and compared basal activity in the nuclei of each patient and activity recorded with different doses. Plasma levels of dexmedetomidine were obtained and correlated with the dose administered. Results: With dexmedetomidine infusion, patients became clinically sedated, and at higher doses (0.5-0.6 mg kg(-1) h(-1)) a significant decrease in the characteristic Parkinsonian subthalamic activity was observed (P<0.05 in beta activity). All subjects awoke to external stimulus over a median of 1 (range: 0-9) min, showing full restoration of subthalamic activity. Dexmedetomidine dose administered and plasma levels showed a positive correlation (repeated measures correlation coefficient=0.504; P<0.001). Conclusions: Patients needing some degree of sedation throughout subthalamic deep brain stimulator implantation for Parkinson's disease can probably receive dexmedetomidine up to 0.6 mg kg(-1) h(-1) without significant alteration of their characteristic subthalamic activity. If patients achieve a 'sedated' state, subthalamic activity decreases, but they can be easily awakened with a non-pharmacological external stimulus and recover baseline subthalamic activity patterns in less than 10 min.

The aim of this narrative review is to confirm that acute pain after craniotomy is frequent and presents with moderate to severe intensity. We also highlight the importance of not only treating post-craniotomy pain, but also of preventing it in order to reduce the incidence of chronic pain. Physicians should be aware that conventional postoperative analgesics (non-steroidal anti-inflammatory, paracetamol, cyclooxygenase inhibitors 2, opioids) are not the only options available. Performing a scalp block prior to surgical incision or after surgery, the use of intraoperative dexmedetomidine, and the perioperative administration of pregabalin are just some alternatives that are gaining ground. The management of post-craniotomy pain should be based on perioperative multimodal analgesia in the framework of an "enhaced recovery after surgery" (ERAS) approach.

Parkinson's disease is characterized by motor and nonmotor symptoms that gradually appear as a consequence of the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Currently, no treatment can slow Parkinson's disease progression. Inasmuch, there is a need to develop animal models that can be used to understand the pathophysiological mechanisms underlying dopaminergic neuron death. The initial goal of this study was to determine if canine adenovirus type 2 (CAV-2) vectors are effective gene transfer tools in the monkey brain. A second objective was to explore the possibility of developing a large nonhuman primate that expresses one of the most common genetic mutations causing Parkinson's disease. Our studies demonstrate the neuronal tropism, retrograde transport, biodistribution, and efficacy of CAV-2 vectors expressing GFP and leucine-rich repeat kinase 2 (LRRK2(G2019S)) in the Macaca fascicularis brain. Our data also suggest that following optimization CAV-2-mediated LRRK2(G2019S) expression could help us model the neurodegenerative processes of this genetic subtype of Parkinson's disease in monkeys.

The aim of this narrative review is to confirm that acute pain after craniotomy is frequent and presents with moderate to severe intensity. We also highlight the importance of not only treating post-craniotomy pain, but also of preventing it in order to reduce the incidence of chronic pain. Physicians should be aware that conventional postoperative analgesics (non-steroidal anti-inflammatory, paracetamol, cyclooxygenase inhibitors 2, opioids) are not the only options available. Performing a scalp block prior to surgical incision or after surgery, the use of intraoperative dexmedetomidine, and the perioperative administration of pregabalin are just some alternatives that are gaining ground. The management of post-craniotomy pain should be based on perioperative multimodal analgesia in the framework of an "enhaced recovery after surgery" (ERAS) approach.

ObjectivesTo evaluate the relationship between pharmacokinetic descriptors of dexmedetomidine (predicted area under the curve during the procedure, predicted plasma level at the end of the procedure, and duration of procedure) and sedation depth (proportion of time with bispectral index <85 during the procedure) with recovery time after ambulatory procedures.Materials and methodsClinical observational study of patients undergoing oral and maxillofacial ambulatory surgery with dexmedetomidine as sole sedative agent. Patients received a loading dose of dexmedetomidine (0.25-1gkg(-1)) followed by a maintenance infusion (0.2-1.4gkg(-1)h(-1)) to keep a bispectral index <85 until 5min before the end of the procedure, and were transferred to a post-anesthesia care unit until criteria for discharge were met.ResultsData from 75 patients was analyzed. Sedation depth was directly associated with recovery time (Pearson correlation coefficient [r]=0.26; p=0.024). Around 7% of the variation in recovery time was explained by the proportion of time with bispectral index <85. No association with procedure duration (r=0.01; p=0.9), predicted area under the curve (r=0.1; p=0.4), or predicted plasma level of dexmedetomidine at the end of the procedure (r=0.12; p=0.3) with recovery time was observed.ConclusionsSedation depth with dexmedetomidine could play a role in increasing recovery time after oral and maxillofacial ambulatory surgery. In our study, the pharmacokinetic descriptors of dexmedetomidine did not seem to influence recovery time.Clinical relevanceSedation depth with dexmedetomidine could play a role in increasing recovery time after ambulatory procedures.

Purpose Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces degeneration of dopaminergic neurons and reproduces the motor features of Parkinson disease (PD); however, the effect of MPTP on extranigral structures has been poorly studied. The aim of this research was to study the cardiac sympathetic innervation of control and MPTP-treated monkeys in order to describe the influence of MPTP toxicity on cardiac tissue. Methods Eight monkeys were included in the study and divided into two groups, four monkeys serving as controls and four forming the MPTP group. Sections from the anterior left ventricle were immunohistochemically examined to characterize the sympathetic fibers of cardiac tissue. The intensity of immunoreactivity in the nerve fibers was quantitatively analyzed using ImageJ software. Results As occurs in PD, the sympathetic peripheral nervous system is affected in MPTP-treated monkeys. The percentage of tyrosine hydroxylase immunoreactive fibers in the entire fascicle area was markedly lower in the MPTP group (24.23%) than the control group (35.27%) (p < 0.05), with preservation of neurofilament immunoreactive fibers in the epicardium of MPTP-treated monkeys. Alpha-synuclein deposits were observed in sections of the anterior left ventricle of MPTP-treated monkeys but not in control animals, whereas phosphorylated synuclein aggregates were not observed in either controls or MPTP-treated monkeys. Conclusion The peripheral autonomic system can also be affected by neurotoxins that specifically inhibit mitochondrial complex I.

For many years the subthalamic nucleus had a poor reputation among neurosurgeons as a result of the acute movement disorders that develop after its lesion or manipulation through different surgical procedures. However, this nucleus is now considered a key structure in relation to parkinsonism, and it is currently one of the preferred therapeutic targets for Parkinson's disease. The implication of the subthalamic nucleus in the pathophysiology of chorea and in the parkinsonian state is thought to be related to its role in modulating the basal ganglia, a fundamental circuit in movement control. Indeed, recent findings have renewed interest in this anatomical structure. Accordingly, this review aims to present a history of the subthalamic nucleus, evolving from the classic surgical concepts associated with the avoidance of this structure, to our current understanding of its importance based on findings from more recent models. Future developments regarding the relationship of the subthalamic nucleus to neuroprotection are also discussed in this review. (c) 2018 International Parkinson and Movement Disorder Society

Objective Subthalamotomy is an effective alternative for the treatment of Parkinson's disease (PD). However, uncertainty about the optimal target location and the possibility of inducing haemichorea-ballism have limited its application. We assessed the correlation between the topography of radiofrequency-based lesions of the subthalamic nucleus (STN) with motor improvement and the emergence of haemichorea-ballism. Methods Sixty-four patients with PD treated with subthalamotomy were evaluated preoperatively and postoperatively using the Unified Parkinson's Disease Rating Scale motor score (UPDRSm), MRI and tractography. Patients were classified according to the degree of clinical motor improvement and dyskinesia scale. Lesions were segmented on MRI and averaged in a standard space. We examined the relationship between the extent of lesion-induced disruption of fibres surrounding the STN and the development of haemichorea-ballism. Results Maximum antiparkinsonian effect was obtained with lesions located within the dorsolateral motor region of the STN as compared with those centre-placed in the dorsal border of the STN and the zona incerta (71.3%, 53.5% and 20.8% UPDRSm reduction, respectively). However, lesions that extended dorsally beyond the STN showed lower probability of causing haemichoreaballism than those placed entirely within the nucleus. Tractography findings indicate that interruption of pallidothalamic fibres probably determines a low probability of haemichorea-ballism postoperatively. Conclusions The topography of the lesion is a major factor in the antiparkinsonian effect of subthalamotomy in patients with PD. Lesions involving the motor STN and pallidothalamic fibres induced significant motor improvement and were associated with a low incidence of haemichorea-ballism.