Virtual hospital and artificial intelligence: a first step towards the application of an innovative health system for the care of rare cerebrovascular diseases.

The development of virtual care options, including virtual hospital platforms, is rapidly changing the healthcare, mostly in the pandemic period, due to difficulties in in-person consultations. For this purpose, in 2020, a neurological Virtual Hospital (NOVHO) pilot study has been implemented, in order to experiment a multidisciplinary second opinion evaluation system for neurological diseases. Cerebrovascular diseases represent a preponderant part of neurological disorders. However, more than 30% of strokes remain of undetermined source, and rare CVD (rCVD) are often misdiagnosed. The lack of data on phenotype and clinical course of rCVD patients makes the diagnosis and the development of therapies challenging. Since the diagnosis and care of rCVDs require adequate expertise and instrumental tools, their management is mostly allocated to a few experienced hospitals, making difficult equity in access to care. Therefore, strategies for virtual consultations are increasingly applied with some advantage for patient management also in peripheral areas. Moreover, health data are becoming increasingly complex and require new technologies to be managed. The use of Artificial Intelligence is beginning to be applied to the healthcare system and together with the Internet of Things will enable the creation of virtual models with predictive abilities, bringing healthcare one step closer to personalized medicine. Herein, we will report on the preliminary results of the NOVHO project and present the methodology of a new project aimed at developing an innovative multidisciplinary and multicentre virtual care model, specific for rCVD (NOVHO-rCVD), which combines the virtual hospital approach and the deep-learning machine system.

Watch brain circulation in unexplained progressive myelopathy: a review of Cognard type V arterio-venous fistulas.

BACKGROUND: Intracranial dural arterio-venous fistulas are pathological anastomoses between arteries and veins located within dural sheets and whose clinical manifestations depend on location and hemodynamic features. They can sometimes display perimedullary venous drainage (Cognard type V fistulas-CVFs) and present as a progressive myelopathy. Our review aims at describing CVFs' variety of clinical presentation, investigating a possible association between diagnostic delay and outcome and assessing whether there is a correlation between clinical and/or radiological signs and clinical outcomes. METHODS: We conducted a systematic search on Pubmed, looking for articles describing patients with CVFs complicated with myelopathy. RESULTS: A total of 72 articles for an overall of 100 patients were selected. The mean age was 56.20 ± 14.07, 72% of patients were man, and 58% received an initial misdiagnosis. CVFs showed a progressive onset in 65% of cases, beginning with motor symptoms in 79% of cases. As for the MRI, 81% presented spinal flow voids. The median time from symptoms' onset to diagnosis was 5 months with longer delays for patients experiencing worse outcomes. Finally, 67.1% of patients showed poor outcomes while the remaining 32.9% obtained a partial-to-full recovery. CONCLUSIONS: We confirmed CVFs' broad clinical spectrum of presentation and found that the outcome is not associated with the severity of the clinical picture at onset, but it has a negative correlation with the length of diagnostic delay. We furthermore underlined the importance of cervico-dorsal perimedullary T1/T2 flow voids as a reliable MRI parameter to orient the diagnosis and distinguish CVFs from most of their mimics.

Paraneoplastic neurological syndromes of the central nervous system: a single institution 7-year case series.

BACKGROUND: Paraneoplastic neurological syndromes (PNSs) are nonmetastatic complications of malignancy, defined by the presence of onconeural antibodies (ONAs). ONAs may be found in 60% of patients with central nervous system (CNS) involvement, and they are directed against intraneuronal antigens or channels, receptors or associated proteins located at the synaptic or extra-synaptic neuronal cell membrane. Given its rare incidence, there are few epidemiological case series on CNS-PNS. We aim to discuss the variability of CNS-PNSs etiology, clinical features, management and outcome, highlighting the importance of early recognition and appropriate treatment, leading to significant reduction of mortality and morbidity. METHODS: We retrospectively reviewed our 7-years single-center experience, and specifically discussed the underlying etiology, parenchymal CNS involvement, and the acute treatment response. Only cases fulfilling PNS Euronetwork criteria for definitive PNS were included. RESULTS: A total of 26 probable PNSs cases involving CNS were identified. We reported medical records of eleven (42.3%) illustrative cases, meeting the criteria of definite PNS and presenting variable clinical spectrum and different radiological appearances. Our series has a relative paucity of the most common syndromes and larger portion of clinical diagnosis with ONAs. Well-characterized ONAs had been detected in CSF of six patients. CONCLUSIONS: Our case series supports the utmost importance of early recognition of CNS-PNSs. Screening for occult malignancies should not be limited to patients with classical CNS syndrome. Empiric immunomodulatory therapy may be considered before the diagnostic evaluation is completed, in order to prevent unfavorable outcome. Late presentations should not discourage initiation of treatment.

SORL1 gene mutation and octapeptide repeat insertion in PRNP gene in a case presenting with rapidly progressive dementia and cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) has been associated with a variety of neurodegenerative disorders, included prion diseases and Alzheimer's disease; its pathophysiology is still largely unknown. We report the case of an 80-year-old man with rapidly progressive dementia and neuroimaging features consistent with CAA carrying two genetic defects in the PRNP and SORL1 genes. METHODS: Neurological examination, brain magnetic resonance imaging (MRI), electroencephalographic-electromyographic (EEG-EMG) polygraphy, and analysis of 14-3-3 and tau proteins, Aß40, and Aß42 in the cerebrospinal fluid (CSF) were performed. The patient underwent a detailed genetic study by next generation sequencing analysis. RESULTS: The patient presented with progressive cognitive dysfunction, generalized myoclonus, and ataxia. Approximately 9 months after symptom onset, he was bed-bound, almost mute, and akinetic. Brain MRI was consistent with CAA. CSF analysis showed high levels of t-tau and p-tau, decreased Aß42, decreased Aß42/Aß40 ratio, and absence of 14.3.3 protein. EEG-EMG polygraphy demonstrated diffuse slowing, frontal theta activity, and generalized spike-waves related to upper limb myoclonus induced by intermittent photic stimulation. Genetic tests revealed the presence of the E270K variant in the SORL1 gene and the presence of a single octapeptide repeat insertion in the coding region of the PRNP gene. CONCLUSIONS: The specific pathogenic contribution of the two DNA variations is difficult to determine without neuropathology; among the possible explanations, we discuss the possibility of their link with CAA. Vascular and degenerative pathways actually interact in a synergistic way, and genetic studies may lead to more insight into pathophysiological mechanisms.

Long-term success of low-frequency subthalamic nucleus stimulation for Parkinson's disease depends on tremor severity and symptom duration.

Patients with Parkinson's disease can develop axial symptoms, including speech, gait and balance difficulties. Chronic high-frequency (>100 Hz) deep brain stimulation can contribute to these impairments while low-frequency stimulation (<100 Hz) may improve symptoms but only in some individuals. Factors predicting which patients benefit from low-frequency stimulation in the long term remain unclear. This study aims to confirm that low-frequency stimulation improves axial symptoms, and to go further to also explore which factors predict the durability of its effects. We recruited patients who developed axial motor symptoms while using high-frequency stimulation and objectively assessed the short-term impact of low-frequency stimulation on axial symptoms, other aspects of motor function and quality of life. A retrospective chart review was then conducted on a larger cohort to identify which patient characteristics were associated with not only the need to trial low-frequency stimulation, but also those which predicted its sustained use. Among 20 prospective patients, low-frequency stimulation objectively improved mean motor and axial symptom severity and quality of life in the short term. Among a retrospective cohort of 168 patients, those with less severe tremor and those in whom axial symptoms had emerged sooner after subthalamic nucleus deep brain stimulation were more likely to be switched to and remain on long-term low-frequency stimulation. These data suggest that low-frequency stimulation results in objective mean improvements in overall motor function and axial symptoms among a group of patients, while individual patient characteristics can predict sustained long-term benefits. Longer follow-up in the context of a larger, controlled, double-blinded study would be required to provide definitive evidence of the role of low-frequency deep brain stimulation.

Migraine and rare neurological disorders.

Although migraine is generally considered an idiopathic and isolated neurological condition, it may also represent the presenting symptom of several uncommon heritable and acquired neurological diseases contributing to the recognition of such conditions. Migraine may indeed present with atypical characteristics or prolonged duration and may be associated with specific neuroradiological findings that may help in identifying the underlying condition. However, features of migraine in rare diseases are usually little known because of the lack of systematic studies. The aim of this paper is to provide clinicians with an updated review on specific clinical and neuroradiological features of migraine in uncommon neurological diseases that may be helpful to their diagnosis and treatment. Therefore, the early diagnosis of these uncommon diseases is crucial for patients' clinical management and for the implementation of therapeutic approaches aimed at targeting the underlying disease pathogenic mechanisms. Thus, when investigating patients affected by migraine, physicians should always be aware about rare causes of migraine that if misdiagnosed could seriously impact patients' outcome. Given these relevant implications, future studies specifically assessing features of migraine in uncommon diseases are mandatory.

Vascular Remodeling in Moyamoya Angiopathy: From Peripheral Blood Mononuclear Cells to Endothelial Cells.

The pathophysiological mechanisms of Moyamoya angiopathy (MA), which is a rare cerebrovascular condition characterized by recurrent ischemic/hemorrhagic strokes, are still largely unknown. An imbalance of vasculogenic/angiogenic mechanisms has been proposed as one possible disease aspect. Circulating endothelial progenitor cells (cEPCs) have been hypothesized to contribute to vascular remodeling of MA, but it remains unclear whether they might be considered a disease effect or have a role in disease pathogenesis. The aim of the present study was to provide a morphological, phenotypical, and functional characterization of the cEPCs from MA patients to uncover their role in the disease pathophysiology. cEPCs were identified from whole blood as CD45dimCD34+CD133+ mononuclear cells. Morphological, biochemical, and functional assays were performed to characterize cEPCs. A significant reduced level of cEPCs was found in blood samples collected from a homogeneous group of adult (mean age 46.86 ± 11.7; 86.36% females), Caucasian, non-operated MA patients with respect to healthy donors (HD; p = 0.032). Since no difference in cEPC characteristics and functionality was observed between MA patients and HD, a defective recruitment mechanism could be involved in the disease pathophysiology. Collectively, our results suggest that cEPC level more than endothelial progenitor cell (EPC) functionality seems to be a potential marker of MA. The validation of our results on a larger population and the correlation with clinical data as well as the use of more complex cellular model could help our understanding of EPC role in MA pathophysiology.

Propranolol for familial cerebral cavernous malformation (Treat_CCM): study protocol for a randomized controlled pilot trial.

BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular malformations characterized by clusters of enlarged leaky capillaries in the central nervous system. They may result in intracranial haemorrhage, epileptic seizure(s), or focal neurological deficits, and potentially lead to severe disability. Globally, CCMs represent the second most common intracranial vascular malformation in humans, and their familial form (FCCMs) accounts for one-fifth of cases. Neurosurgical excision, and perhaps stereotactic radiosurgery, is the only available therapeutic option. Case reports suggest that propranolol might modify disease progression. METHODS: Treat_CCM is a prospective, randomized, open-label, blinded endpoint (PROBE), parallel-group trial involving six Italian clinical centres with central reading of brain magnetic resonance imaging (MRI) and adverse events. Patients with symptomatic FCCMs are randomized (2:1 ratio) either to propranolol (40-80 mg twice daily) in addition to standard care or to standard care alone (i.e. anti-epileptic drugs or headache treatments). The primary outcome is intracranial haemorrhage or focal neurological deficit attributable to CCMs. The secondary outcomes are MRI changes over time (i.e. de novo CCM lesions, CCM size and signal characteristics, iron deposition, and vascular leakage as assessed by quantitative susceptibility mapping and dynamic contrast enhanced permeability), disability, health-related quality of life, depression severity, and anxiety (SF-36, BDI-II, State-Trait Anxiety Inventory). DISCUSSION: Treat_CCM will evaluate the safety and efficacy of propranolol for CCMs following promising case reports in a randomized controlled trial. The direction of effect on the primary outcome and the consistency of effects on the secondary outcomes (even if none of them yield statistically significant differences) of this external pilot study may lead to a larger sample size in a definitive phase 2 trial. TRIAL REGISTRATION: ClinicalTrails.gov, NCT03589014. Retrospectively registered on 17 July 2018.

Understanding the Pathophysiology of Cerebral Amyloid Angiopathy.

Cerebral amyloid angiopathy (CAA), one of the main types of cerebral small vessel disease, is a major cause of spontaneous intracerebral haemorrhage and an important contributor to cognitive decline in elderly patients. Despite the number of experimental in vitro studies and animal models, the pathophysiology of CAA is still largely unknown. Although several pathogenic mechanisms including an unbalance between production and clearance of amyloid beta (Aß) protein as well as 'the prion hypothesis' have been invoked as possible disease triggers, they do not explain completely the disease pathogenesis. This incomplete disease knowledge limits the implementation of treatments able to prevent or halt the clinical progression. The continuous increase of CAA patients makes imperative the development of suitable experimental in vitro or animal models to identify disease biomarkers and new pharmacological treatments that could be administered in the early disease stages to prevent irreversible changes and disease progression.

CADASIL as Multiple Sclerosis Mimic: A 48-year-old man with severe leukoencephalopathy and spinal cord involvement.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a common cause of inherited stroke in young adults. CADASIL causes extensive white matter T2 hyperintensities at brain MRI, in particular involving anterior-temporal lobes and external capsules; usually, there is no spinal cord involvement. Since CADASIL clinical spectrum is heterogeneous and MRI findings are sometimes not specific, Multiple Sclerosis (MS) represents a frequent CADASIL misdiagnosis. Herein, we describe the case of a 48-year-old man affected by CADASIL and referred to our clinic with an initial diagnosis of secondary progressive MS because of diffuse leukoencephalopathy and spinal cord lesions at MRI.

Discovering the Italian phenotype of cerebral amyloid angiopathy (CAA): the SENECA project.

Cerebral amyloid angiopathy (CAA) is one of the major types of cerebral small vessel disease, and a leading cause of spontaneous intracerebral hemorrhage and cognitive decline in elderly patients. Although increasingly detected, a number of aspects including the pathophysiology, the clinical and neuroradiological phenotype, and the disease course are still under investigation. The incomplete knowledge of the disease limits the implementation of evidence-based guidelines on patient's clinical management and the development of treatments able to prevent or reduce disease progression. The SENECA (SEarchiNg biomarkErs of Cerebral Angiopathy) project is the first Italian multicenter cohort study aimed at better defining the disease natural history and identifying clinical and neuroradiological markers of disease progression. By a multidisciplinary approach and the collection of a large and well-phenotyped series and biorepository of CAA patients, the study is ultimately expected to improve the diagnosis and the knowledge of CAA pathophysiological mechanisms.

Deep brain stimulation in Parkinson's disease: A multicentric, long-term, observational pilot study.

BACKGROUND: The impact of deep brain stimulation (DBS) on cognitive and urinary disorders, falls, and eventually hospitalizations and mortality in Parkinson's disease (PD) is still debated. OBJECTIVE: We compared the rates of dementia, mild cognitive impairment (MCI), urinary incontinence, nocturia, falls, hospitalizations, and mortality in a cohort of PD patients undergoing DBS with a cohort of medically-treated patients chosen as controls. METHODS: We conducted a retrospective pilot study in six Italian DBS centers. 91 PD patients receiving DBS and 91 age- and gender-matched controls receiving the best medical treatment alone with a minimum follow-up of one year were enrolled. Clinical data were collected from baseline to the last follow-up visit using an ad-hoc developed web-based system. RESULTS: The risk of dementia was similar in the two groups while patients in the surgical cohort had lower rates of MCI, urinary incontinence, nocturia, and falls. In contrast, the risk of hospital admissions related to PD was higher in the surgical cohort. However, when excluding hospitalizations related to DBS surgery, the difference between the two cohorts was not significant. The surgical cohort had a lower number of hospitalizations not related to PD. The risk of death was similar in the two groups. CONCLUSION: Despite a higher risk of hospitalization, patients receiving DBS had a lower rate of MCI, urinary incontinence, nocturia and falls, without evidence of an increased risk of dementia and mortality. Although these findings need to be confirmed in prospective studies, they seem to suggest that DBS may play a significant role in the management of non-motor symptoms and common complications of advanced PD.

Asymmetric STN DBS for FOG in Parkinson's disease: A pilot trial.

BACKGROUND: In Parkinson's disease (PD), freezing of gait (FOG) is a highly disabling gait disorder. Though deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficient treatment for advanced PD, the management of STN DBS refractory FOG remains challenging. OBJECTIVE: To evaluate the long-term impact on FOG of unilateral stimulation reduction in PD treated with bilateral STN DBS. METHODS: Patients with bilateral STN DBS for at least one year and refractory FOG were included in a randomized, double blind, cross-over clinical trial. They were randomized to chronic (CHR) vs. experimental (EXP) stimulation (30% amplitude reduction contralateral to the least affected body side), each condition for 4 weeks. Gait and FOG were assessed both in the OFF and ON medication conditions. Primary outcome was the difference in the FOG percentage during gait assessment and in a composite gait score in CHR vs. EXP stimulation. RESULTS: The study was stopped early for futility. Of the 12 patients included, eight dropped out because of re-emerging of PD symptoms. In the four patients who sustained the experimental condition, the FOG percentage did not improve, whether in the OFF (CHR: 13.4% vs. EXP: 16.8%) or in the ON (CHR: 19.5% vs. EXP: 19.8%) medication condition. There was no change in the composite gait score (CHR: 5.5 ±â€¯1.3 vs. EXP: 6.3 ±â€¯3.3). CONCLUSIONS: Most patients did not tolerate the unilateral amplitude reduction of STN DBS in the long-term. Moreover, this strategy failed to improve FOG in patients who could sustain the procedure. CLINICALTRIAL. GOV IDENTIFIER: NCT02704195.

Risk of Infection After Local Field Potential Recording from Externalized Deep Brain Stimulation Leads in Parkinson's Disease.

OBJECTIVE: Adaptive deep brain stimulation (aDBS) controlled by local field potentials (LFPs) is considered a promising treatment for advanced Parkinson's disease (PD). The clinical research investigating aDBS functioning is performed using external deep brain stimulation (DBS) systems that require LFP recording through the temporary externalization of DBS leads. Although research examining LFP was first undertaken more than 20 years ago, only a few studies concern lead externalization and LFP recording safety. In the present retrospective study, we assessed the risk of infection related to these procedures. METHODS: A total of 105 patients with PD who underwent DBS surgery and lead externalization at our hospital from 2002 to 2014 were included in the present study. The medical records were used to collect clinical data and information concerning surgical site infections. We assessed the infection incidence in our cohort and the risk of infection related to the LFP recording procedure. RESULTS: The incidence of infections in patients who underwent lead externalization was 2.8%, which was consistent with the postoperative infectious risk reported in the literature (Wilcoxon signed rank test; P > 0.05). Moreover, the LFP recording procedure did not significantly increase the infection risk (LFP recordings vs. no LFP recordings: 2.5% vs. 4.2%; Fisher exact test; P > 0.05). CONCLUSIONS: DBS lead externalization and LFP recording are safe and do not increase the postoperative infection risk in patients with PD who undergo DBS surgery. Our retrospective study supported further clinical research in the field of LFP-based aDBS.

Deep Brain Stimulation during Pregnancy and Delivery: Experience from a Series of "DBS Babies".

INTRODUCTION: Deep brain stimulation (DBS) is widely used to improve quality of life in movement disorders (MD) and psychiatric diseases. Even though the ability to have children has a big impact on patients' life, only a few studies describe the role of DBS in pregnancy. OBJECTIVE: To describe risks and management of women treated by DBS for disabling MD or psychiatric diseases during pregnancy and delivery. METHODS: We report a retrospective case series of women, followed in two DBS centers, who became pregnant and went on to give birth to a child while suffering from disabling MD or psychiatric diseases [Parkinson's disease, dystonia, Tourette's syndrome (TS), Obsessive Compulsive Disorder (OCD)] treated by DBS. Clinical status, complications and management before, during, and after pregnancy are reported. Two illustrative cases are described in greater detail. RESULTS: DBS improved motor and behavioral disorders in all patients and allowed reduction in, or even total interruption of disease-specific medication during pregnancy. With the exception of the spontaneous early abortion of one fetus in a twin pregnancy, all pregnancies were uneventful in terms of obstetric and pediatric management. DBS parameters were adjusted in five patients in order to limit clinical worsening during pregnancy. Implanted material limited breast-feeding in one patient because of local pain at submammal stimulator site and led to local discomfort related to stretching of the cable with increasing belly size in another patient whose stimulator was implanted in the abdominal wall. CONCLUSION: Not only is it safe for young women with MD, TS and OCD who have a DBS-System implanted to become pregnant and give birth to a baby but DBS seems to be the key to becoming pregnant, having children, and thus greatly improves quality of life.

The effects of levodopa and deep brain stimulation on subthalamic local field low-frequency oscillations in Parkinson's disease.

New adaptive systems for deep brain stimulation (DBS) could in the near future optimize stimulation settings online so as to achieve better control over the clinical fluctuations in Parkinson's disease (PD). Local field potentials (LFPs) recorded from the subthalamic nucleus (STN) in PD patients show that levodopa and DBS modulate STN oscillations. Because previous research has shown that levodopa and DBS variably influence beta LFP activity (8-20 Hz), we designed this study to find out how they affect low-frequency (LF) oscillations (2-7 Hz). STN LFPs were recorded in 19 patients with PD during DBS, after levodopa medication, and during DBS and levodopa intake combined. We investigated the relationship between LF modulations, DBS duration and levodopa intake. We also studied whether LF power depended on disease severity, the patient's clinical condition and whether LF modulations were related to electrode impedances. LF power increased during DBS, after levodopa intake and under both experimental conditions combined. The LF power increase correlated with the levodopa-induced clinical improvement and the higher the electrode impedance, the greater was the LF power change. These data suggest that the LF band could be useful as a control neurosignal for developing novel adaptive DBS systems for patients with PD.

Transcutaneous spinal direct current stimulation.

In the past 10 years renewed interest has centered on non-invasive transcutaneous weak direct currents applied over the scalp to modulate cortical excitability ("brain polarization" or transcranial direct current stimulation, tDCS). Extensive literature shows that tDCS induces marked changes in cortical excitability that outlast stimulation. Aiming at developing a new, non-invasive, approach to spinal cord neuromodulation we assessed the after-effects of thoracic transcutaneous spinal DC stimulation (tsDCS) on somatosensory potentials (SEPs) evoked in healthy subjects by posterior tibial nerve (PTN) stimulation. Our findings showed that thoracic anodal tsDCS depresses the cervico-medullary PTN-SEP component (P30) without eliciting adverse effects. tsDCS also modulates post-activation H-reflex dynamics. Later works further confirmed that transcutaneous electric fields modulate spinal cord function. Subsequent studies in our laboratory showed that tsDCS modulates the flexion reflex in the human lower limb. Besides influencing the laser evoked potentials (LEPs), tsDCS increases pain tolerance in healthy subjects. Hence, though the underlying mechanisms remain speculative, tsDCS modulates activity in lemniscal, spinothalamic, and segmental motor systems. Here we review currently available experimental evidence that non-invasive spinal cord stimulation (SCS) influences spinal function in humans and argue that, by focally modulating spinal excitability, tsDCS could provide a novel therapeutic tool complementary to drugs and invasive SCS in managing various pathologic conditions, including pain.

Subthalamic local field potentials after seven-year deep brain stimulation in Parkinson's disease.

Studies describing subthalamic (STN) local field potentials (LFPs) recorded during deep brain stimulation (DBS) in patients with Parkinson's disease (PD), within the first month after DBS electrode implant, show that DBS modulates specific STN oscillations: whereas low-frequency (LF) oscillations (2-7 Hz) increase, beta oscillations (8-30 Hz) variably decrease. No data show whether LFPs remain stable for longer than one month after DBS surgery. Having long-term information is essential especially for use as a long-term feedback control signal for adaptive DBS systems. To evaluate how STN activity behaves years after prolonged chronic stimulation in PD we studied STN LFPs at rest without DBS and during ongoing DBS, in 11 parkinsonian patients 7 years (7.54±1.04) after STN electrode implantation for DBS (hyperchronic group) and in 16 patients 3 days after STN electrode implantation (acute group). STN LF and beta-band LFPs recorded at rest at 7 years contained almost the same information as those recorded at 3 days. STN recordings showed similar LFP responses to DBS in the acute and hyperchronic stages: whereas during ongoing DBS the LF power band increased for the whole population, beta activity decreased only in nuclei with significant beta activity at baseline. The LF/beta power ratio in all nuclei changed in both study groups, suggesting that this variable might be an even more informative marker of PD than the single LF and beta bands. Because STN LFP activity patterns and STN LFP responses to DBS stay almost unchanged for years after DBS electrode implantation they should provide a consistent feedback control signal for adaptive DBS.