The Genetic Etiology of Parkinson's Disease Does Not Robustly Affect Subthalamic Physiology.

BACKGROUND: It is unknown whether Parkinson's disease (PD) genetic heterogeneity, leading to phenotypic and pathological variability, is also associated with variability in the unique PD electrophysiological signature. Such variability might have practical implications for adaptive deep brain stimulation (DBS). OBJECTIVE: The aim of our work was to study the electrophysiological activity in the subthalamic nucleus (STN) of patients with PD with pathogenic variants in different disease-causing genes. METHODS: Electrophysiological data from participants with negative genetic tests were compared with those from GBA, LRRK2, and PRKN-PD. RESULTS: We analyzed data from 93 STN trajectories (GBA-PD: 28, LRRK2-PD: 22, PARK-PD: 10, idiopathic PD: 33) of 52 individuals who underwent DBS surgery. Characteristics of ß oscillatory activity in the dorsolateral motor part of the STN were similar for patients with negative genetic tests and for patients with different forms of monogenic PD. CONCLUSIONS: The genetic heterogeneity in PD is not associated with electrophysiological differences. Therefore, similar adaptive DBS algorithms would be applicable to genetically heterogeneous patient populations. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Pathophysiology of Watershed Infarction: A Three-Dimensional Time-of-Flight Magnetic Resonance Angiography Study.

BACKGROUND: Most of the time, watershed infarcts (WIs) involve steno-occlusive carotid disease. The pathophysiological mechanism could be predicted by their pattern: internal WIs (IWIs) are thought to be due to hemodynamic impairment in contrast to cortical WIs (CWIs), which are more likely to be caused by microembolic phenomena. We used a 3D time-of-flight (TOF) magnetic resonance angiography (MRA) study to assess this hypothesis. METHODS: In 45 consecutive patients with a recent WI and ipsilateral cervical carotid stenosis, clinical and radiological data were obtained retrospectively. 3D TOF MRA were analyzed both qualitatively and quantitatively (internal carotid and anterior, middle and posterior cerebral arteries). Then, 2 groups were determined depending on their radiological patterns: WIs with (IWI+) or without (IWI-) an internal watershed. RESULTS: Thirty-two of the 45 patients (71%) had IWIs that were or were not associated with CWIs (IWI+), while 13 patients (29%) had only CWIs (IWI-). There was no significant relationship between the radiological pattern and the demographic data, the cardiovascular risk factors, or the degree of stenosis. However, IWI+ patients more frequently had motor weakness (P = .03) than CWI patients. An ipsilateral reduced middle cerebral artery intensity on 3D TOF MRA in both qualitative and quantitative analyses was significantly associated with IWI+. Instead within IWI-, no significantly reduced signal intensity was found. CONCLUSION: These findings originally support the view that IWIs are mainly caused by a hemodynamic impairment related to carotid stenosis, whereas CWIs are mostly due to a microembolic mechanism. 3D TOF MRA, which gives pertinent information on pathophysiology on IWIs, can help in decision making.

Delayed levodopa-responsive parkinsonism following acute midbrain injury.

Acute midbrain injury may cause both hyperkinetic movement disorders and parkinsonism. The temporal interval between the insult and the emergence of hyperkinetic disorders can last years. A delayed appearance of parkinsonism, on the other hand, was rarely described. We present three cases of male patients (50-, 58- and 28-year-old) who developed levodopa-responsive parkinsonism 20, 8 and two years, respectively, after acute brain insult involving the midbrain. Insults included subcortical intracerebral hemorrhage dissecting into the midbrain, embolic basilar occlusion and trauma. A fluorodopa scan, performed in two cases, revealed reduced striatal uptake. All individuals improved on low doses of levodopa and developed motor fluctuations shortly after levodopa was introduced. We conclude that delayed, levodopa-responsive parkinsonism following midbrain injury should be recognized in the relevant clinical setup. Possible mechanisms include age-related loss of dopaminergic neurons superimposed on acute injury and secondary neurodegeneration.

Development of health technology assessment in France.

OBJECTIVES: The aim of this study was to describe the history of health technology assessment (HTA) in France. METHODS: The approach was a descriptive review done by people who have been very much involved in this history. RESULTS: The interest in HTA and evaluation as a tool for health decision making goes back to the 1970s in France. During the 1980s, there were several attempts to develop a national HTA agency, which finally came to fruition with the development of the Agence Nationale de l'Evaluation Medicale (ANDEM) in 1989. ANDEM's main success, perhaps, was in making HTA known in France by developing its own assessments, writing and validating appropriate methodologies for assessing medical technology and medical practices, and by organizing in France the development of programs of consensus development conferences, which the ANDEM either organized itself or supported and validated. In the mid-1990s, the mandate of ANDEM was extended to hospital accreditation and the agency's name was changed to Agence Nationale d'Accreditation et d'Evaluation en Sante (ANAES). Finally, in 2005, the National Authority for Health (HAS) was formed to consolidate efforts to centralize the programs of HTA, aiming at helping decision making regarding reimbursement and pricing, in one agency and to define the optimal use of health technology in France. CONCLUSIONS: HTA has become a strong influence in the healthcare system in France. These developments may be considered rather typical of the approach to public policy questions in France, where regulation is more in use than in other countries (at least in the healthcare field). At the same time, this approach has made lobbying and other attempts to influence decisions common as well, so one might say that HTA is more politicized than in some other countries in Europe.

Patterns of Acute Ischemic Strokes After Carotid Endarterectomy and Therapeutic Implications.

AIM: Acute ischemic strokes following surgical treatment of carotid stenosis lead to substantial disability and mortality, and vascular mechanisms underlying their development are not fully elucidated. The goal of this study was to analyze the topographic patterns of acute ischemic stroke following carotid endarterectomy (CEA) on diffusion-weighted and perfusion-weighted magnetic resonance imaging (MRI). MATERIAL AND METHODS: Data were retrospectively collected from consecutive patients who underwent CEA and developed postoperative acute ischemic stroke. Based on the MRI data sets, the lesion patterns of acute stoke were characterized. Morphology of the circle of Willis, the 3-D time-of-flight (3D-TOF) of the cerebral arteries, and status of the carotid circulation were also analyzed in order to determine the vascular mechanisms involved in stroke development. RESULTS: Between January 2008 and May 2015, 821 patients were treated surgically for a symptomatic or asymptomatic carotid stenosis at the University Hospital of Nice. Nineteen (2.3%) patients had an acute ischemic stroke after surgery. Among them, 11 (57.9%) patients had a territorial infarction and 8 (42.1%) patients had an internal watershed infarction, cortical watershed infarction, or mixed border zone infarction. According to imaging data sets, embolic mechanism of stroke was reported for 12 (63.2%) patients, hemodynamic mechanism for 2 (10.5%) patients, and mixed mechanism for 5 (26.3%) patients. An asymmetry on 3D-TOF was observed in 60% and 50% of patients with hemodynamic and mixed stroke and in 25% of patients with embolic stroke. The latter 2 patients with embolic stroke underwent successful mechanical thrombectomy using stent-retriever devices. CONCLUSION: In this cohort, embolic mechanism leading to postoperative stroke was more frequently observed than hemodynamic mechanism. Immediate characterization of the cerebral lesion by postoperative brain MRI is of utmost importance because it may rapidly identify patients eligible for treatments such as mechanical thrombectomy.