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Introduction Coronavirus disease 2019 (COVID-19) is associated to neuromuscular symptoms in up to 10.7% of hospitalized patients. Nevertheless, the extent of muscular involvement in infected subjects with no signs of myopathy has never been assessed with neurophysiological investigations. Methods Over a 3-week period — from April 30 through May 20, 2020 — a total of 70 patients were hospitalized in the Internal Medicine Ward of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan, Italy. After excluding patients who underwent invasive ventilation and steroid treatment, 12 patients were evaluated. Nerve conduction studies (NCS) included the analysis of conduction velocity, amplitude, and latency for bilateral motor tibial, ulnar nerves, and sensory sural and radial nerves. Unilateral concentric-needle electromyography (EMG) was performed evaluating at least 4 areas of 8 selected muscles. For each muscle, spontaneous activity at rest, morphology, and recruitment of motor unit action potentials (MUAPs) were evaluated. Results While nerve conduction studies were unremarkable, needle electromyography showed myopathic changes in 6 out of 12 subjects. All patients were asymptomatic for muscular involvement. Clinical features and laboratory findings did not show relevant differences between patients with and without myopathic changes. Conclusion Our data show that in SARS-CoV-2 infection muscular involvement can occur despite the absence of clinical signs or symptoms and should be considered part of the disease spectrum. The application of muscle biopsy to unravel the mechanisms of myofiber damage on tissue specimens could help to clarify the pathogenesis and the treatment response of coronavirus-mediated injury. Supplementary Information The online version contains supplementary material available at 10.1007/s10072-021-05469-8.

Objective: Hereditary spastic paraplegia (HSP) represents a heterogeneous group of neurodegenerative diseases characterized by progressive spasticity and lower limb weakness. We assessed the effects of transcutaneous spinal direct current stimulation (tsDCS) in HSP. Design: A double-blind, randomized, crossover and sham-controlled study. Setting: Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan. Participants: eleven patients with HSP (six men, mean age ± SD: 37.3 ± 8.1 years), eight affected by spastin/SPG4,1 by atlastin1/SPG3a, 1 by paraplegin/SPG7 and 1 by ZFYVE26/SPG15. Interventions: tsDCS (anodal or sham, 2.0 mA, 20’, five days) delivered over the thoracic spinal cord (T10-T12). Outcome measures: Motor-evoked potentials (MEPs), the H-reflex (Hr), F-waves, the Ashworth scale for clinical spasticity, the Five Minutes Walking test and the Spastic Paraplegia Rating Scale (SPRS) were assessed. Patients were evaluated before tsDCS (T0), at the end of the stimulation (T1), after one week (T2), one month (T3) and two months (T4). Results: The score of the Ashworth scale improved in the anodal compared with sham group, up to two months following the end of stimulation (T1, P = .0137; T4, P = .0244), whereas the Five Minutes Walking test and SPRS did not differ between the two groups. Among neurophysiological measures, both anodal and sham tsDCS left Hr, F-waves and MEPs unchanged over time. Conclusions: Anodal tsDCS significantly decreases spasticity and might be a complementary strategy for the treatment of spasticity in HSP.

Background and purpose The aim of this study was to define the prevalence and characteristics of peri-electrode edema in a prospective cohort of patients undergoing deep brain stimulation (DBS) surgery and to correlate it with clinical findings. Methods We performed brain magnetic resonance imaging (MRI) between 7 and 20 days after surgery in 19 consecutive patients undergoing DBS surgery for Parkinson's disease. The T2-weighted hyperintensity surrounding DBS leads was characterized and quantified. Any evidence of bleeding around the leads was also evaluated. Clinical and follow-up data were recorded. In a subgroup of patients, a follow-up MRI was performed 3-6 weeks after surgery. We also retrospectively reviewed the post-operative computed tomography scans of patients who underwent DBS at our center since 2013. Results Magnetic resonance imaging showed a peri-lead edematous reaction in all (100%) patients, which was unilateral in three patients (15.8%). In six patients (31.6%), we detected minor peri-lead hemorrhage. Edema completely resolved in eight out of 11 patients with a follow-up MRI and was markedly reduced in the others. Most patients were asymptomatic but six (31.6%) manifested various degrees of confusional state without motor symptoms. We found no significant correlation between edema volume, distribution and any clinical feature, including new post-operative neurological symptoms. The retrospective computed tomography analysis showed that peri-electrode hypodensity consistent with edema is absent at early post-operative imaging but is common at scans performed >3 days after surgery. Conclusions Peri-electrode edema is a common, transient reaction to DBS lead placement and a convincing relation between edema and post-operative clinical status is lacking.

Music-based interventions seem to enhance motor, sensory and cognitive functions in Parkinson’s disease (PD), but the underlying action mechanisms are still largely unknown. This electroencephalography (EEG) study aimed to investigate the effective connectivity patterns characterizing PD in the resting state and during music listening. EEG recordings were obtained from fourteen non-demented PD patients and 12 healthy controls, at rest and while listening to three music tracks. Theta- and alpha-band power spectral density and multivariate partial directed coherence were computed. Power and connectivity measures were compared between patients and controls in the four conditions and in music vs. rest. Compared to controls, patients showed enhanced theta-band power and slightly enhanced alpha-band power, but markedly reduced theta- and alpha-band interactions among EEG channels, especially concerning the information received by the right central channel. EEG power differences were partially reduced by music listening, which induced power increases in controls but not in patients. Connectivity differences were slightly compensated by music, whose effects largely depended on the track. In PD, music enhanced the frontotemporal inter-hemispheric communication. Our findings suggest that PD is characterized by enhanced activity but reduced information flow within the EEG network, being only partially normalized by music. Nevertheless, music capability to facilitate inter-hemispheric communication might underlie its beneficial effects on PD pathophysiology and should be further investigated.

Background: Subthalamic deep brain stimulation (STN-DBS) effects may decrease with Parkinson’s disease (PD) progression. There is no indication if, when, and how to consider the interruption of DBS treatment in late-stage PD. The objective of the current study was to investigate the percentage of “poor stimulation responders” among late-stage PD patients for elaborating an algorithm to decide whether and when DBS discontinuation may be considered. Methods: Late-stage PD patients (Hoehn Yahr stage ≥4 and Schwab and England Scale

Purpose Patients with Parkinson's disease (PD) variably report sexual dysfunctions. We assessed sexuality in PD by comparing sexual function between a large group of patients with idiopathic PD and a group of subjects without PD. Methods We recruited 121 patients with mild-to-moderate PD (aged 40–80 years) from four Italian Movement Disorder Clinics and 123 non-Parkinsonian controls (NPC) (aged 40–80 years). Sexual function was assessed with four scales: the Brief Index of Sexual Functioning (BISF-M for men; BISF-W for women), the International Index of Erectile Function (IIEF), and the Female Sexual Function Index (FSFI). Both groups also underwent assessment with the Beck Depression Inventory (BDI) and the Mini Mental State Examination (MMSE), and patients were assessed with the Parkinson's Disease Questionnaire-8 (PDQ-8). Results No differences in total score were found between PD and NPC for any sexual function scale (BISF-M, BISF-W, IIEF, FSFI: p > 0.05). However, the Orgasm/Pleasure Domain (BISF, D5) was significantly lower in male patients than in controls. Conclusion Our findings fail to confirm previous findings that PD is associated with a significant sexual impairment. NPC and patients with PD have comparable sexual function in both sexes. Thus, rather than dismissing sexual dysfunction as a normal parkinsonian symptom, physicians should refer patients to sexual medicine specialists who can investigate and discuss problems fully, diagnose possible comorbidities, and suggest appropriate treatments.

Multiple System Atrophy is a severe neurodegenerative disorder which is characterized by a variable clinical presentation and a broad neuropathological spectrum. The pathogenic mechanisms are almost completely unknown. In the present study, we established a cellular model of MSA by using fibroblasts' primary cultures and performed several experiments to investigate the causative mechanisms of the disease, with a particular focus on mitochondrial functioning. Fibroblasts' analyses (7 MSA-P, 7 MSA-C and 6 healthy controls) displayed several anomalies in patients: an impairment of respiratory chain activity, in particular for succinate Coenzyme Q reductase (p

The future of deep brain stimulation (DBS) for Parkinson's disease (PD) lies in new closed‐loop systems that continuously supply the implanted stimulator with new settings obtained by analyzing a feedback signal related to the patient's current clinical condition.1 The most suitable feedback for PD is subthalamic local field potential (LFP) activity recorded from the stimulating electrode itself.2, 3, 4 This closed‐loop technology known as adaptive DBS (aDBS) recently proved superior to conventional open‐loop DBS (cDBS) in patients with PD.2 No studies have yet tested aDBS in freely moving humans for a prolonged time. This information is an essential prerequisite for developing new implantable aDBS devices for chronic PD treatment. In this single‐case study, we tested whether a portable DBS device we developed is suitable to compare the clinical benefit in a freely moving PD patient induced by either aDBS or cDBS. To do so, after a first experimental session for extracting patient settings to personalize the aDBS algorithm, we treated a blinded patient (51 y old, male, 8 y PD history) with cDBS and aDBS in two separate experimental sessions each lasting 120 min, 5 and 6 d, respectively, after DBS electrode implant. To ensure reliable results, the patient underwent repeated clinical assessments every 20 min (T1‐T5) by two independent blinded neurologists through Unified Parkinson's Disease Rating Scale (UPDRS) III subsections and Rush Dyskinesia Rating Scale (see Supplemental Data for details).

Although deep brain stimulation (DBS) surgery rarely leads to complications, when it does they can be serious (Fenoy and Simpson, 2014). In a recent study about DBS surgery complications in movement disorders, postoperative imaging demonstrated that asymptomatic intracerebral hemorrhage (ICH) occurs in 0.5% of patients, asymptomatic intraventricular hemorrhage in 3.4%, symptomatic ICH in 1.1%, and ischemic infarction in 0.4% (Fenoy and Simpson, 2014). Local field potentials (LFPs) are oscillatory bioelectrical signals arising from large neuronal ensembles around an electrode inserted into the central nervous system. LFP originating from deep human brain structures can be recorded through the electrodes used for DBS in various pathological conditions. For instance, in Parkinson’s disease (PD) LFP beta activity (13–30 Hz) is typically recorded in the off-medication state and when DBS is turned off. Levodopa treatment and DBS (Giannicola et al., 2010) both suppress beta activity and the degree of suppression correlates with motor improvement. Though recordings from the subthalamic nucleus (STN) are mainly used for experimental purposes they could be useful for monitoring DBS surgery: Chen and colleagues (Chen et al., 2006) showed that intra-operative LFP recordings help identifying the STN by disclosing specific beta activity. We report the case of a patient in whom LFP recordings disclosed abnormal STN activity before complications related to DBS became clinically and neuroradiologically evident.

Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique inducing prolonged brain excitability changes and promoting cerebral plasticity, is a promising option for neurorehabilitation. Here, we review progress in research on tDCS and language functions and on the potential role of tDCS in the treatment of post-stroke aphasia. Currently available data suggest that tDCS over language-related brain areas can modulate linguistic abilities in healthy individuals and can improve language performance in patients with aphasia. Whether the results obtained in experimental conditions are functionally important for the quality of life of patients and their caregivers remains unclear. Despite the fact that important variables are yet to be determined, tDCS combined with rehabilitation techniques seems a promising therapeutic option for aphasia.

Transcranial direct current stimulation (tDCS) is a non-invasive technique for inducing prolonged functional changes in the human cerebral cortex. This simple and safe neurostimulation technique for modulating motor functions in Parkinson's disease could extend treatment option for patients with movement disorders. We assessed whether tDCS applied daily over the cerebellum (cerebellar tDCS) and motor cortex (M1-tDCS) improves motor and cognitive symptoms and levodopa-induced dyskinesias in patients with Parkinson's disease (PD). Nine patients (aged 60-85 years; four women; HoehnYahr scale score 2-3) diagnosed as having idiopathic PD were recruited. To evaluate how tDCS (cerebellar tDCS or M1-tDCS) affects motor and cognitive function in PD, we delivered bilateral anodal (2 mA, 20 min, five consecutive days) and sham tDCS, in random order, in three separate experimental sessions held at least 1 month apart. In each session, as outcome variables, patients underwent the Unified Parkinson's Disease Rating Scale (UPDRS III and IV) and cognitive testing before treatment (baseline), when treatment ended on day 5 (T1), 1 week later (T2), and then 4 weeks later (T3), at the same time each day. After patients received anodal cerebellar tDCS and M1-tDCS for five days, the UPDRS IV (dyskinesias section) improved (p 0.001). Conversely, sham tDCS, cerebellar tDCS, and M1-tDCS left the other variables studied unchanged (p 0.05). Despite the small sample size, our preliminary results show that anodal tDCS applied for five consecutive days over the motor cortical areas and cerebellum improves parkinsonian patients' levodopa-induced dyskinesias.

Background The thalamus is a deep-seated and crucial structure for the sensorimotor system. It has been long considered a surgically inaccessible area because of the morbidity associated with surgical resections. Astrocytomas of the thalamus are usually treated with bioptic procedures followed by adjuvant treatments. Intraoperative neurophysiologic monitoring (IONM) allows safe and satisfactory resections of lobar gliomas, but few data are available for thalamic lesions. The aim of this study was to review the outcome of a small series of patients with thalamic astrocytomas that were treated with surgical resection with the aid of IONM. Methods Surgical resection with IONM was performed in 5 patients with thalamic astrocytomas (1 grade I, 1 grade II, 2 grade III, 1 grade IV). Two astrocytomas were in the dominant hemisphere. Preoperative and postoperative neuropsychological assessments were performed in 3 patients. IONM was tailored to the individual patient and consisted of transcranial motor evoked potential monitoring, cortical motor evoked potential monitoring, somatosensory evoked potential monitoring, direct electrical stimulation, electroencephalography, and electrocorticography. Results None of the patients experienced permanent motor deficits; 2 patients had a transient hemiparesis requiring rehabilitation; 1 patient had a transient aphasia, and 1 patient had permanent aphasia. None of the patients had intraoperative seizures, but 1 patient experienced postoperative transient status epilepticus. The extent of resection on postoperative volumetric magnetic resonance imaging was >70% in all cases. Conclusions Surgical resection of thalamic astrocytomas appeared to be effective and relatively safe when guided by IONM. Larger series of patients are required to confirm these preliminary data.

COQ2 mutations have been implicated in the etiology of multiple system atrophy (MSA) in Japan. However, several genetic screenings have not confirmed the role of its variants in the disease. We performed COQ2 sequence analysis in 87 probable MSA. A homozygous change p.A43G was found in an MSA-C patient. Cosegregation analysis and the evaluation of CoQ10 content in muscle and fibroblasts did not support the pathogenic role of this variant.

Introduction The possibility that deep brain stimulation (DBS) in Parkinson's disease (PD) alters patients' decisions and actions, even temporarily, raises important clinical, ethical and legal questions. Abnormal moral decision-making can lead to ethical rules violations. Previous experiments demonstrated the subthalamic (STN) activation during moral decision-making. Here we aim to study whether STN DBS can affect moral decision-making in PD patients. Methods Eleven patients with PD and bilateral STN DBS implant performed a computerized moral task in ON and OFF stimulation conditions. A control group of PD patients without DBS implant performed the same experimental protocol. All patients underwent motor, cognitive and psychological assessments. Results STN stimulation was not able to modify neither reaction times nor responses to moral task both when we compared the ON and the OFF state in the same patient (reaction times, p = .416) and when we compared DBS patients with those treated only with the best medical treatment (reaction times: p = .408, responses: p = .776). Conclusions Moral judgment is the result of a complex process, requiring cognitive executive functions, problem-solving, anticipations of consequences of an action, conflict processing, emotional evaluation of context and of possible outcomes, and involving different brain areas and neural circuits. Our data show that STN DBS leaves unaffected moral decisions thus implying relevant clinical and ethical implications for DBS consequences on patients' behavior, on decision-making and on judgment ability. In conclusion, the technique can be considered safe on moral behavior.

The pathophysiological mechanisms responsible for conduction block in multifocal motor neuropathy (MMN) are still unclear. To clarify the physiological abnormalities at the site of the block, we tested the effects induced by polarizing direct currents on motor conduction along forearm nerves in 25 normal nerves (13 subjects), and at the site of conduction block in six nerves (five patients) with MMN. In healthy controls, whereas nerve depolarization failed to change the conditioned compound muscle action potential (CMAP), hyperpolarization elicited a significant, charge-dependent, decrease in the conditioned CMAP size. Hyperpolarization with 4 mC elicited CMAPs that were 86.76 +/- 5.22% (mean +/- SEM) of the control unconditioned response (P < 0.05). Analysis of individual MMN nerves showed that polarizing currents elicited markedly heterogeneous effects: depending on the nerve tested, depolarization or hyperpolarization in most cases significantly improved conduction along motor fibres across the conduction block. In three MMN nerves, pathophysiological abnormalities were consistent with a hyperpolarizing block, in two with a depolarizing block, and in one with a mixed block. Our observations indicate that the pathophysiological abnormalities at the site of conduction block in MMN may arise from depolarization or hyperpolarization, probably depending on the course of disease.

INTRODUCTION: Intra-operative neurophysiological monitoring and brain mapping techniques represent nowadays the gold standard for surgical resection of brain tumors. Brain mapping usually requires the exposure of a large area of brain cortex in order to identify the different eloquent sites (e.g. primary motor strip, speech arrest sites). Thus, relatively large classic fronto-temporal craniotomies are generally performed. Nevertheless, in recent years the use of small craniotomies targeted on the tumor has gained popularity thanks to Neuronavigation systems and to the low morbidity rates associated with shorter surgical procedures and reduced anesthestic drug administration. Aim of this study was to review our experience which combines extensive neurophysiological monitoring and small craniotomies. Length of surgical time, intra-operative and post-operative complications, length of stay, extent of resection rate and the neurological outcomes were assessed. PATIENTS AND METHODS: Eighty-five consecutive patients (54 Males, 31 Females; Median Age 55 years, range 12-77) underwent surgery with brain mapping and intra-operative neurophysiological monitoring for resection of a brain tumor in eloquent location under asleep-asleep (62 patients) or asleep-awake (23 patients) anesthesia. Pre- and post-operative assessment included in-depth neuropsychological evaluation and MRI. Tumor histologies were the following: 74 gliomas (60 HGG, 14 LGG), 6 metastases and 5 other tumor histologies (2 cavernomas, 2, meningiomas, 1 AVM). The bone flap was tailored to the size of the tumor; no cortex other than that which was strictly necessary for tumor resection was exposed. The intra-operative neurophysiological monitoring included: EEG, SSEP, transcranial MEP and/or cortical MEP, ECoG; direct electrical stimulation (DES) was performed using bipolar and monopolar probes. RESULTS: Median surgical time was 230 minutes (range 90-390). Intra-operative complications included 9 seizures (3 requiring pharmacological treatment, 6 regressing after cold irrigation) and 5 electrical seizure. Post-operative neurosurgical complications were the following: 8 seizures and 4 re-operation for hematoma. Seventy-three patients (86%) could be discharged home while 12 (14%) were transferred to rehabilitation. In only 3 patients (3.5%) a permanent new neurological deficit could be noted at 3-month follow-up. Median post-operative stay was 7 days (range 3-45). CONCLUSIONS: In our experience a small craniotomy supported by extensive neurophysiological monitoring and brain mapping permitted to achieve satisfactory results in terms of complications, hospitalization, and neurological outcomes.

A 51-year-old man, from Romania, was referred to our metabolic disease clinic for a dyslipidemia characterized by low total cholesterol (TC) and high triglycerides (TG). He had no family history of cardiovascular and metabolic diseases. He was married with three children: a 14-year-old son, a 9-year-old daughter and a 15-year-old daughter. He had undergone tonsillectomy for recurrent tonsillitis as a child. When he was 20, he was admitted to the Neurology Department of Colentina Hospital (Bucharest) for weakness of the lower limbs with balance and gait disturbances, associated with fever. During the hospitalization, a biopsy of the sural muscle was performed, and the discharge diagnosis was Stark-Kaeser syndrome. The patient reported a progressive improvement of his symptoms, after acupuncture sessions. Currently, he reports a slight weakness of the lower limbs only after prolonged exercise. The rest of his history is unremarkable. He denies taking prescription medications or over-the-counter supplements. His weight was 66.3 kg, body mass index (BMI) 25.3 kg/m, waist circumference 89 cm, blood pressure 120/80, pulse 64 beats per minute. Cardiorespiratory, abdominal and neurological examinations were normal. In particular, tendinous xanthomas, xanthelasmas and corneal arcus were absent. Laboratory tests showed low high-density lipoprotein cholesterol (HDL-C = 1 mg/dl) and TC (48 mg/dl); TG were not detectable because of lipemic serum. After a 15-day hypolipidemic diet, the repeat laboratory tests (Table 1), confirmed the almost complete absence of HDLC, low levels of TC and low-density cholesterol (LDL-C) and mild hypertriglyceridemia. Apolipoprotein A-I (Apo A-I) was undetectable, apolipoprotein A-II (Apo A-II) was almost absent; apolipoprotein B (Apo B) was reduced, while apolipoprotein C-II (Apo C-II), apolipoprotein C-III (Apo C-III) and lipoprotein(a) [Lp(a)] were within normal limits. The Apolipoprotein E genotype was e2/e4. There was also thrombocytopenia, a slight anemia with stomatocytes on a peripheral blood smear (Fig. 1), hyperferritinemia. Aminotransferase (AST), LDH, total and direct bilirubin were slightly high, while haptoglobin and reticulocytes were normal. The two most common mutations in the HFE gene (HFE Cys282[Tyr, HFE His63[Asp), associated with hyperferritinemia, were absent. Laboratory tests also revealed a previous A and B hepatitis. Abdominal ultrasound showed splenomegaly (longitudinal spleen diameter 14.5 cm). Ophthalmologic examination did not reveal any corneal opacity. The electrocardiogram was normal, exercise stress test showed some abnormalities in the ST-T segment at peak exercise; a stress-rest perfusion myocardial scintigraphy was performed and was negative for inducible ischemia. Doppler ultrasound of the supra-aortic T. Lucchi (&) L. Assolari B. Arosio Metabolic Diseases Clinic, Geriatric Operating Unit, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy e-mail: tlucchi@policlinico.mi.it

Multifocal motor neuropathy (MMN) is a rare disorder of the peripheral nervous system characterised by the presence of focal motor conduction blocks. Although the pathological basis of conduction block is believed to be focal demyelination, in multifocal motor neuropathy this mechanism lacks definitive proof from morphological studies. In recent years special neurophysiological techniques for assessing axonal excitability non-invasively in humans have expanded knowledge on the pathophysiology of multifocal motor neuropathy. Nonetheless, several findings support the hypothesis that conduction blocks probably arise from more than one pathogenetic mechanism (hyperpolarisation or depolarisation) which can change during the course of the disease and probably represent the "tip of the iceberg" of axo-myelinic abnormalities.

In the past ten 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, 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 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 spinal cord stimulation in managing various pathologic conditions, including pain.

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.

Transcranial direct current stimulation (tDCS), a technique for central neuromodulation, has been recently proposed as possible treatment in several neurological and psychiatric diseases. Although shifts on focal brain excitability have been proposed to explain the clinical effects of tDCS, how tDCS-induced functional changes influence cortical interneurones is still largely unknown. The assessment of short latency afferent inhibition (SLAI) of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS), provides the opportunity to test non-invasively interneuronal cholinergic circuits in the human motor cortex. The aim of the present study was to assess whether anodal tDCS can modulate interneuronal circuits involved in SLAI. Resting motor threshold (RMT), amplitude of unconditioned MEPs and SLAI were assessed in the dominant hemisphere of 12 healthy subjects (aged 21-37) before and after anodal tDCS (primary motor cortex, 13min, 1mA). SLAI was assessed delivering electrical conditioning stimuli to the median nerve at the wrist prior to test TMS given at the interstimulus interval (ISI) of 2ms. Whereas RMT and the amplitude of unconditioned MEPs did not change after anodal tDCS, SLAI significantly increased. In conclusion, anodal tDCS-induced effects depend also on the modulation of cortical interneuronal circuits. The enhancement of cortical cholinergic activity assessed by SLAI could be an important mechanism explaining anodal tDCS action in several pathological conditions.

Aiming at developing a new, noninvasive approach to spinal cord neuromodulation, we evaluated whether transcutaneous direct current (DC) stimulation induces long-lasting changes in the central pain pathways in human beings. A double-blind crossover design was used to investigate the effects of anodal direct current (2mA, 15min) applied on the skin overlying the thoracic spinal cord on the lower-limb flexion reflex in a group of 11 healthy volunteers. To investigate whether transcutaneous spinal cord DC stimulation (tsDCS) acts indirectly on the nociceptive reflex by modulating excitability in mono-oligosynaptic segmental reflex pathways, we also evaluated the H-reflex size from soleus muscle after tibial nerve stimulation. In our healthy subjects, anodal thoracic tsDCS reduced the total lower-limb flexion reflex area by 40.25% immediately after stimulation (T0) and by 46.9% 30min after stimulation offset (T30). When we analyzed the 2 lower-limb flexion reflex components (RII tactile and RIII nociceptive) separately, we found that anodal tsDCS induced a significant reduction in RIII area with a slight but not significant effect on RII area. After anodal tsDCS, the RIII area decreased by 27% at T0 and by 28% at T30. Both sham and active tsDCS left all the tested H-reflex variables unchanged. None of our subjects reported adverse effects after active stimulation. These results suggest that tsDCS holds promise as a tool that is complementary or alternative to drugs and invasive spinal cord electrical stimulation for managing pain. Thoracic transcutaneous direct current stimulation induces depression of nociceptive lower limb flexion reflex in human beings that persists after stimulation offset; this form of stimulation holds promise as a tool that is complementary or alternative to drugs and invasive spinal cord electrical stimulation for managing pain.

Corrigendum to ‘Ethical safety of deep brain stimulation: A study on moral decision-making in Parkinson's disease’ [Park. Relat. Disord. 21 (2015) 709e716] Manuela Fumagalli , Sara Marceglia , Filippo Cogiamanian , Gianluca Ardolino , Marta Picascia , Sergio Barbieri , Gabriella Pravettoni d, , Claudio Pacchetti , Alberto Priori a, f, * a Centro Clinico per la Neurostimolazione, le Neurotecnologie ed i Disordini del Movimento, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Milan, Italy b U.O. Neurofisiopatologia, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Milan, Italy c Unit a Operativa Parkinson e Disordini del Movimento, IRCCS Istituto Neurologico Mondino, Via Mondino 2, Pavia, Italy d Dipartimento di Economia, Management e Metodi Quantitativi, Universit a degli Studi di Milano, Via Festa del Perdono 7, Milan, Italy e Applied Research Unit for Cognitive and Psychological Science, Istituto Europeo di Oncologia, Via Giuseppe Ripamonti 435, Milan, Italy f Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Universit a degli Studi di Milano, Via Francesco Sforza 35, Milan, Italy

This work is the second of a series of papers in which we investigated the neurophysiological basis of deep brain stimulation (DBS) clinical efficacy using post-operative local field potential (LFP) recordings from DBS electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease. We found that low-frequency (1–1.5 Hz) oscillations in LFP recordings from the STN of patients with Parkinson's disease dramatically increase after DBS of the STN itself (log power change = 0.93 ± 0.62; Wilcoxon: p = 0.0002, n = 13), slowly decaying to baseline levels after turning DBS off. The DBS-induced increase of low-frequency LFP oscillations is highly reproducible and appears only after the delivery of DBS for a time long enough to induce clinical improvement. This increase of low-frequency LFP oscillations could reflect stimulation-induced modulation of network activity or could represent changes of the electrochemical properties at the brain–electrode interface.

Astrocytes associated with beta-amyloid (Abeta) accumulate in senile plaques of Alzheimer's disease (AD). To investigate the biological effects of Abeta/astrocyte interaction, we examined chemokine production by the human astrocytoma cell line U373MG stimulated with Abeta peptides. Northern blot analysis and specific immunoassays demonstrate that Abeta [1-42] and Abeta [25-35] induce mRNA expression and release of monocyte chemotactic protein (MCP)-1 but not of gamma-interferon inducible protein (IP)-10 by U373MG cells. The observation that Abeta induces astrocyte production of the potent microglia chemoattractant MCP-1 contributes to understanding mechanism of damage exerted by Abeta in AD senile plaques.

We read with interest the article by Klein et al 1 providing pathological evidence that the neuropathic attacks in hereditary brachial plexus neuropathy (HBPN) are secondary to an inflammatory process. As a possible pathogenetic mechanism the authors suggest altered immune modulation. In the absence of controlled clinical trials they treated patients with intravenous methyl prednisolone. This treatment—in their experience—relieved the symptoms, particularly the pain, for a brief time, but as they tapered the corticosteroid dose the signs and symptoms reappeared. The authors concluded that in some cases of HBPN an inflammatory multifocal response arising from an immune dysfunction in the brachial plexus and upper limb nerves causes nerve abnormalities and axonal degeneration. Treatments based on immune modulation may therefore be useful in the management of HBPN. To further support the immunological pathogenesis we describe a 13 year old girl who since childhood had suffered from recurrent episodes of severe asymmetric pain and weakness of the shoulder and arm involving the same as well as the opposite side. Her father had similar attacks and genetic testing for hereditary neuropathy with liability to pressure palsy was negative. At the age of 4 years the girl experienced severe left shoulder pain that lasted for 20 days and was treated with corticosteroids. Three years later, a left deltoid muscle hypotrophy …

INTRODUCTION: The thalamus is a deep-seated and crucial structure for the sensory-motor system. It has been longly considered a surgically inaccessible area due to the morbidity associated with surgical resections. In fact, astrocytomas of the thalamus usually undergo bioptic procedures followed by adjuvant treatments (if indicated). Intra-operative neurophysiological monitoring (IONM) allows safe and satisfactory resections of lobar gliomas. Considering the need of reliable specimens for the pathological diagnosis and that the extent of resection is positively associated with overall survival, aim of this study was to review the feasibility and outcome of a small series of patients with thalamic astrocytomas operated with the aid of IONM. PATIENTS AND METHODS: Five patients with thalamic astrocytomas (1 grade I, 3 grade III, 1 grade IV) underwent surgical resection with IONM. Two astrocytomas were in the dominant hemisphere. All patients performed pre-operative and post-operative neuropsychological assessment. IONM consisted in transcranial MEP monitoring (4 patients), cortical MEP monitoring (2 patients), direct electrical stimulation (5 patients), EEG (5 patients) and ECoG monitoring (2 patients). Anesthesia was totally intra-venous (propofol + remifentanyl) for all patients; 1 patients was operated following an asleep-awake protocol, 4 following an asleep-asleep protocol. RESULTS: None of patients suffered from permanent motor deficits; 2 patients had a transient hemiparesis requiring rehabilitation; 1 patient suffered a transient aphasia, and 1 patient had permanent aphasia. None of the patients had intraoperative seizures, but 1 patient had a post-operative transient status epilepticus. Resection was total or subtotal in 3 cases and partial (with resection between 50 and 80% of the tumor volume) in the other 2 cases. CONCLUSIONS: Surgical resection of thalamic astrocytomas could be meaningful and relatively safe when guided by IONM. Larger series of patients are required to confirm this preliminary data.