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Functional outcome in patients with postanoxic encephalopathy after cardiac arrest (CA) often remains unclear, and there is a strong need of new prognostication measures. We aimed at investigating serum neurofilament light (NfL) chain concentration in patients with a postanoxic encephalopathy after CA and its prognostic potential. Serum samples were prospectively collected at different time points after CA in consecutive patients admitted to the intensive care unit (ICU) of Ticino Cardiocentre (Lugano, Switzerland) between June 2017 and March 2018. Serum NfL concentration was measured using a single molecule array (SIMOA) assay. The association of NfL levels with time to return of spontaneous circulation (ROSC), serum neuronal specific enolase (NSE) concentration, time between CA and sample collection, electroencephalogram (EEG) pattern and clinical outcome (death status at one month) were explored. Fourteen patients experiencing 15 CAs were included in the study (median age = 58 (57-68) years, 8 males). Median serum NfL concentration was 1027.0 (25.5-6033.7) pg/ml. There were positive associations between serum NfL and time to ROSC (rho = 0.60, p 0.0001), NSE concentration (rho = 0.76, p 0.0001), and severity of brain damage as estimated by EEG, with the highest concentrations measured in patients with suppressed electrical activity (14,954.0 [9006.0-25,364.0] pg/ml). Neurofilament light concentration remained high in samples collected up to 17 days after CA. Median NfL levels were higher among dead than alive patients at one month (6401.7 [3768.5-15,573.3] vs 25.5 [25.2-75.4] pg/ml). High NfL levels performed better than NSE in predicting death status at one month (NfL area under the curve (AUC) = 0.98, 95% confidence interval (CI) = 0.94-1.00; NSE AUC = 0.80, 95% CI = 0.67-0.94). These results support the potential inclusion of serum NfL in the battery of prognostication measures to be used in patients with postanoxic encephalopathy in ICU settings. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Summary Purpose: The endocannabinoid system is involved in excitatory/inhibitory balance mechanisms within the central nervous system (CNS). Growing evidence shows that its perturbation leads to development of epileptic seizures in experimental models, thus indicating that endocannabinoids play an intrinsic protective role in suppressing pathologic neuronal excitability. Experimental data also demonstrate that the endocannabinoid anandamide (AEA) can antagonize epileptic discharges in hippocampal tissue. The objective of our study was to measure endocannabinoids levels in the cerebrospinal fluid (CSF) of drug-naive patients affected by temporal lobe epilepsy (TLE). Methods: We measured the levels of both AEA and the other endocannabinoid, 2-arachidonoylglycerol (2-AG), in the CSF of drug-naive patients with TLE. Results: A significant reduction of AEA was found in the CSF of patients with compared with healthy controls (epileptic patients = 2.55 ± 1.78 pmol/ml; healthy controls = 11.65 ± 7.53 pmol/ml; n = 9 for both groups, p

Of the endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG) have received the most study. A functional interaction between these molecules has never been described. Using mouse brain slices, we found that stimulation of metabotropic glutamate 5 receptors by 3,5-dihydroxyphenylglycine (DHPG) depressed inhibitory transmission in the striatum through selective involvement of 2-AG metabolism and stimulation of presynaptic CB1 receptors. Elevation of AEA concentrations by pharmacological or genetic inhibition of AEA degradation reduced the levels, metabolism and physiological effects of 2-AG. Exogenous AEA and the stable AEA analog methanandamide inhibited basal and DHPG-stimulated 2-AG production, confirming that AEA is responsible for the downregulation of the other eCB. AEA is an endovanilloid substance, and the stimulation of transient receptor potential vanilloid 1 (TRPV1) channels mimicked the effects of endogenous AEA on 2-AG metabolism through a previously unknown glutathione-dependent pathway. Consistently, the interaction between AEA and 2-AG was lost after pharmacological and genetic inactivation of TRPV1 channels.

Objective: To investigate whether repetitive transcranial magnetic stimulation (rTMS) can modify spasticity.Methods: We used high-frequency (5 Hz) and low-frequency (1 Hz) rTMS protocols in 19 remitting patients with relapsing–remitting multiple sclerosis and lower limb spasticity.Results: A single session of 1 Hz rTMS over the leg primary motor cortex increased H/M amplitude ratio of the soleus H reflex, a reliable neurophysiologic measure of stretch reflex. Five hertz rTMS decreased H/M amplitude ratio of the soleus H reflex and increased corticospinal excitability. Single sessions did not induce any effect on spasticity. A significant improvement of lower limb spasticity was observed when rTMS applications were repeated during a 2-week period. Clinical improvement was long-lasting (at least 7 days after the end of treatment) when the patients underwent 5 Hz rTMS treatment during a 2-week protocol. No effect was obtained after a 2-week sham stimulation.Conclusions: Repetitive transcranial magnetic stimulation may improve spasticity in multiple sclerosis.

Restless legs syndrome (RLS)/Willis-Ekbom disease is 3-fold more prevalent in pregnant than in non-pregnant women. Symptoms are particularly strong and frequent during the third trimester of pregnancy and disappear around delivery. A pre-existing form of RLS tends to worsen during pregnancy. Women who experience RLS during pregnancy have a higher risk of symptoms in further pregnancies and of developing a primary form of RLS later in life, than women free of symptoms during pregnancy. This article reviews the literature for pregnancy-related RLS, with particular attention to its epidemiology, course, possible mechanisms, management, and the impact of symptoms.

We tested the effects of 5-Hz rTMS over the motor cortex in multiple sclerosis (MS) subjects complaining of lower urinary tract symptoms either in the filling or voiding phase. Our data show that motor cortex stimulation for five consecutive days over two weeks ameliorates the voiding phase of the micturition cycle, suggesting that enhancing corticospinal tract excitability might be useful to ameliorate detrusor contraction and/or urethral sphincter relaxation in MS patients with bladder dysfunction. Multiple Sclerosis 2007; 13: 269–271. http://msj.sagepub.com

Background Chronic, intermittent exposure to psychostimulant drugs results in striatal neuroadaptations leading to an increase in an array of behavioral responses on subsequent challenge days. A brain-specific striatal-enriched tyrosine phosphatase (STEP) regulates synaptic strengthening by dephosphorylating and inactivating several key synaptic proteins. This study tests the hypothesis that a substrate-trapping form of STEP will prevent the development of amphetamine-induced stereotypies. Methods A substrate-trapping STEP protein, TAT-STEP (C-S), was infused into the ventrolateral striatum on each of 5 consecutive exposure days and 1 hour before amphetamine injection. Animals were challenged to see whether sensitization to the stereotypy-producing effects of amphetamine developed. The same TAT-STEP (C-S) protein was used on acute striatal slices to determine the impact on long-term potentiation and depression. Results Infusion of TAT-STEP (C-S) blocks the increase of amphetamine-induced stereotypies when given during the 5-day period of sensitization. The TAT-STEP (C-S) has no effect if only infused on the challenge day. Treatment of acute striatal slices with TAT-STEP (C-S) blocks the induction of long-term potentiation and potentates long-term depression. Conclusions A substrate trapping form of STEP blocks the induction of amphetamine-induced neuroplasticity within the ventrolateral striatum and supports the hypothesis that STEP functions as a tonic break on synaptic strengthening.

We tested the effects of 5-Hz repetitive transcranial magnetic stimulation (rTMS) over the motor cortex in multiple sclerosis (MS) subjects with cerebellar symptoms. rTMS improved hand dexterity in cerebellar patients ( n = 8) but not in healthy subjects ( n = 7), as detected by a significant transient reduction of the time required to complete the nine-hole pegboard task. rTMS of the motor cortex may be a useful approach to treat cerebellar impairment in MS patients.

Decreased activity of mitochondrial complex I and II is implicated in the pathophysiology of progressive supranuclear palsy (PSP) and Huntington's disease (HD), respectively. Both disorders preferentially affect the nucleus striatum, a brain area particularly vulnerable to excitotoxic damage. To gain insights into the pathophysiology of neuronal degeneration during PSP and HD, here we studied the possible interplay between excitatory transmission and mitochondrial complex I and II inhibition in the development of striatal damage. By using in vitro neurophysiological recordings and cell swelling measures in corticostriatal slices, we found that stimulation of NMDA receptors significantly contributed to the neurotoxic effects of 3-nitropropionic acid (3-NP) but not of rotenone, selective inhibitors of mitochondrial complex II and I, respectively. We also found that blockade of a subset of NMDA receptors containing the NR2B subunit was sufficient to protect the striatum from the injurious effects of 3-NP, an effect unrelated to the prevention of membrane excitation by NMDA receptor stimulation. Pharmacological inhibition of dopamine receptors, conversely, failed to modulate both rotenone- and 3-NP-induced neuronal damage. Our results indicate that the cellular mechanisms leading to striatal neuronal death are different following inhibition of distinct mitochondrial complexes of the respiratory chain, implying that neuroprotective strategies in PSP and HD must significantly differ.

Background One of the earliest neurochemical alterations observed in both Huntington’s disease (HD) patients and HD animal models is the dysregulation of the endocannabinoid system, an alteration that precedes the development of identifiable striatal neuropathology. How this alteration impacts striatal synaptic transmission is unknown. Methods We measured the effects of cannabinoid receptor stimulation on γ-aminobutyric acid (GABA)-ergic synaptic currents recorded from striatal neurons of R6/2 HD mice in the early phase of their disease. Results The sensitivity of striatal GABA synapses to cannabinoid receptor stimulation is severely impaired in R6/2 HD mice. In particular, whereas in control animals activation of cannabinoid CB1 receptors results in a significant inhibition of both evoked and spontaneous GABA-mediated synaptic events by a presynaptic mechanism, in R6/2 mice this treatment fails to reduce GABA currents but causes, in contrast, a slight increase of spontaneous inhibitory postsynaptic currents (sIPSCs). Conclusions Experimental HD was also associated with enhanced frequency of sIPSCs, a result consistent with the conclusion that loss of cannabinoid-mediated control of GABA transmission might contribute to hyperactivity of GABA synapses in the striatum of HD mice. Accordingly, spontaneous excitatory postsynaptic currents, which were not upregulated in R6/2 mice, were still sensitive to cannabinoid receptor stimulation.