D. Ciampi de Andrade

COGNITIVE IMPAIRMENT AND DEMENTIA IN NEUROCYSTICERCOSIS: A CROSS-SECTIONAL CONTROLLED STUDY

COGNITIVE IMPAIRMENT AND DEMENTIA IN NEUROCYSTICERCOSIS: A CROSSSECTIONAL CONTROLLED STUDY To the Editor: Ciampi de Andrade et al.1 report that two-thirds of patients with neurocysticercosis (NCYST) show cognitive impairment and attributed this to a synergistic interaction of cysticercus lesions and local inflammation.1 We believe that other possible mechanisms for cognitive dysfunction in NCYST should be considered. NCYST affects brain regions that are distant from the location of the cysticerci.2 For example, cysticercosis might cause hippocampal dysfunction prompting epilepsy or cognitive impairment even when lesions are located outside the limbic system.2 Although inflammation may be a cause, other more sophisticated biologic mechanisms related to host– parasite interactions need to be addressed. Parasites may induce expression of several classes of genes in the CNS of the host and exceeds the gene expression seen in inflammatory processes.3 These genes encode proteins or neuropeptides involved in the regulation of vital physiologic and behavioral processes,3 which have led to the behavioral manipulation hypothesis.4 Toxoplasma gondii manipulates the behavior of its intermediate rat host in order to increase its chance of being preyed on by cats, its definitive feline host, ensuring the completion of its life cycle.4 Taenia crassiceps infection in mice is an experimental model for Taenia solium cysticercosis in man.5 In this murine model, cysticercosis induces male feminization characterized by estrogenization, deandrogenization, and loss of sexual and aggressive patterns of behavior.5 Intraperitoneal T crassiceps infection induces a specific increase of c-fos expression in the hypothalamus, hippocampus, and cortex of mice.5 These findings indicate that even intraperitoneal cysticercosis provokes CNS changes that underlie behavioral abnormalities in this infection.5 These observations add a new dimension to parasite–host interaction that may be significant. It is possible that the human brain might also be affected by NCYST in ways that should not be underestimated. We hypothesize that NCYST might also cause cognitive abnormalities in the human brain by mechanisms other than brain damage or inflammation. The studies of such mechanisms will likely improve our knowledge of the clinical manifestations of NCYST and its treatment.

Sensory abnormalities and pain in Parkinson disease and its modulation by treatment of motor symptoms.

Pain and sensory abnormalities are present in a large proportion of Parkinson disease (PD) patients and have a significant negative impact in quality of life. It remains undetermined whether pain occurs secondary to motor impairment and to which extent it can be relieved by improvement of motor symptoms. The aim of this review was to examine the current knowledge on the mechanisms behind sensory changes and pain in PD and to assess the modulatory effects of motor treatment on these sensory abnormalities. A comprehensive literature search was performed. We selected studies investigating sensory changes and pain in PD and the effects of levodopa administration and deep brain stimulation (DBS) on these symptoms. PD patients have altered sensory and pain thresholds in the off‐medication state. Both levodopa and DBS improve motor symptoms (i.e.: bradykinesia, tremor) and change sensory abnormalities towards normal levels. However, there is no direct correlation between sensory/pain changes and motor improvement, suggesting that motor and non‐motor symptoms do not necessarily share the same mechanisms. Whether dopamine and DBS have a real antinociceptive effect or simply a modulatory effect in pain perception remain uncertain. These data may provide useful insights into a mechanism‐based approach to pain in PD, pointing out the role of the dopaminergic system in pain perception and the importance of the characterization of different pain syndromes related to PD before specific treatment can be instituted.

Into the Island: A new technique of non-invasive cortical stimulation of the insula

STUDY AIM We describe a new neuronavigation-guided technique to target the posterior-superior insula (PSI) using a cooled-double-cone coil for deep cortical stimulation. INTRODUCTION Despite the analgesic effects brought about by repetitive transcranial magnetic stimulation (TMS) to the primary motor and prefrontal cortices, a significant proportion of patients remain symptomatic. This encouraged the search for new targets that may provide stronger pain relief. There is growing evidence that the posterior insula is implicated in the integration of painful stimuli in different pain syndromes and in homeostatic thermal integration. METHODS The primary motor cortex representation of the lower leg was used to calculate the motor threshold and thus, estimate the intensity of PSI stimulation. RESULTS Seven healthy volunteers were stimulated at 10 Hz to the right PSI and showed subjective changes in cold perception. The technique was safe and well tolerated. CONCLUSIONS The right posterior-superior insula is worth being considered in future studies as a possible target for rTMS stimulation in chronic pain patients.

Isolated CNS Whipple disease with a variant of oculofacial—skeletal myorhythmia (OFSM)

A 62-year-old woman presented with insidious onset of depressive mood and progressive difficulties with daily activities. She had no diarrhea, abdominal cramps, arthralgia, weight loss, or palpable lymphadenopathy. Physical examination revealed fever, delirium, bilateral upper motor neuron signs, and myorhythmic movements …

Beyond weakness: Characterization of pain, sensory profile and conditioned pain modulation in patients with motor neuron disease: A controlled study

Motor neuron diseases (MND) represent a group of disorders that evolve with inexorable muscle weakness and medical management is based on symptom control. However, deeper characterization of non‐motor symptoms in these patients have been rarely reported.

How to look for deep dynamic mechanical sensitivity

In this issue of the European Journal of Pain you will find the article by Mar ıa Palacios Ce~ na and collaborators (2017) entitled ‘Assessment of Dynamic Mechanical Sensitivity in Individuals with Tension Type Headache: The Dynamic Pressure Algometry’. In this study, the authors’ goal was to further explore a new dimension in quantitative sensory testing (QST): dynamic pressure algometry (DPA). Regular ‘static’ pressure algometry fails to provide a clear spatial distribution of pressure hyperalgesia areas, which can be readily obtained by rolling devices able to capture the slow adaptation properties of sensitized nociceptors by assessing a large volume of tissue in one stroke and thus providing ‘pressure sensitivity maps’. As acknowledged by the authors, this would be analogous to the assessment of dynamic mechanical allodynia with a brush, as opposed to the static mechanical allodynia explored with graded monofilaments (Fig. 1). Indeed, dynamic and static pressure algometry seem to explore two distinct, although probably overlapping, types of deep tissue sensitivity. In the present article, this new QST parameter was used to obtain dynamic pressure thresholds (DPT) in patients with tension type headaches (TTH), according to current appropriate criteria (Headache Classification Committee of the International Headache Society (IHS), 2013). The main aims were to investigate the potential correlations between DPTs and headache characteristics or widespread pressure sensitivity assessed by standard static pressure algometry. The results showed that the correlation between dynamic and standard static pressure pain thresholds was moderate in all the points assessed and the coefficient of determination (r) was between 28% and 43%. These results mean that less than half of DPT variance is explained by PPT alone. Thus, authors’ hypothesis seems verified as the two parameters are only partly correlated and measure two different types of deep sensitivity. Although this new tool could be helpful to investigate deep sensitivity, confirmatory studies are needed in different pain conditions. One major limitation of this study is the absence of a control group. The inclusion of matched healthy volunteers would have allowed concluding whether TTH patients present with hyperalgesia or allodynia. In the future, normative data must be obtained in healthy subjects of different ages, as previously done in various body parts for a set of quantitative sensory tests (Rolke et al., 2006; Marcuzzi et al., 2017).

Tiefe Hirnstimulation reduziert Schmerz bei M. Parkinson

Die tiefe Hirnstimulation des Subthalamus reduziert Schmerz und andere nicht motorische Symptome bei M. Parkinson. Zu diesem Ergebnis kamen die Arzte um R. Cury vom Schmerzzentrum der Neurologischen Abteilung der Universitat von Sao Paulo in Brasilien.

P11-26 Long term analgesic efficacy of transcranial magnetic stimulation of the motor cortex in patients with fibromyalgia

Results: Significant reduction of the SICI and decrease of the rMT were observed in patients with NPH compared to young control subjects and age-matched patients with peripheral neuropathy. At baseline, these changes were not correlated with severity of walking disturbances. However, there was a significant relationship between enhancement of the SICI and improvement of the motor performance following ventricular shunting. Conclusion: The results of this study suggest that NPH affects corticospinal excitability causing a disinhibition of the motor cortex.

P20-26 Neuropharmacological basis of repetitive transcranial magnetic stimulation (rTMS) induced analgesia: the role of endogenous opioids

Background: It has been shown that rTMS to the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) can reduce pain in experimental models in healthy subjects. The mechanisms may depend on the activation of pain modulation systems. Due to the major role of endogenous opioids systems (EOS) in pain modulation, we hypothesized that EOS are involved in the analgesic action of rTMS. Methods: To investigate the role of EOS in rTMS-induced analgesia, we compared the analgesic effects of M1 or DLPFC stimulation before and after naloxone or placebo, using a randomized double-blind design. Twelve healthy volunteers were randomly assigned to three groups and received either active stimulation of the right M1, active stimulation of the right DLPFC (frequency 10 Hz, 80% of the motor threshold, 1500 pulses/session) or sham stimulation, during two experimental sessions within two weeks interval. Based on our previous results showing that rTMS acts preferentially on cold pain [1], measurements of cold pain thresholds were used to evaluate the analgesic effects of rTMS. During each session, cold pain thresholds were measured on the left thenar eminence before and one hour after iv injection of naloxone or saline (bolus of 0.1 mg/kg then continuous infusion of 0.1 mg/kg/h up to the end of rTMS). Results: Compared with the sham stimulation, both the stimulation of M1 and DLPFC induced a significant decrease in cold pain (i.e. analgesia) after saline injection. Naloxone significantly reduced the analgesic effects of M1, but not of DLPFC stimulation. Conclusions: We showed for the first time that EOS are involved in the analgesic effects of rTMS. The differential effects of naloxone on M1 and DLPFC stimulation indicate that, despite their apparent similarity, the analgesic effects evoked by stimulation of these cortical sites involve distinct mechanisms.

215 CEREBRAL PLASTICITY IN PAINFUL PHANTOM LIMB: A STUDY WITH TRANSCRANIAL MAGNETIC STIMULATION AND FUNCTIONAL MAGNETIC RESONANCE IMAGING

in chronic pain patients. Little is known about pain perception in healthy volunteers with high neuroticism scores. Our aim was to use fMRI to investigate differences in central pain processing of a tonic painful stimulus, in young, healthy volunteers with high neuroticism scores, compared to matched low neuroticism scorers. Methods: Neuroticism (N) was assessed with the Eysenck Personality Questionnaire (EPQ). Two age-matched groups of 12 volunteers (high N: mean EPQ: 17, mean age 24.9) (low N: mean EPQ 2.2, mean age 24.4) underwent a functional scan, during which 30-second thermal stimuli of a moderate pain intensity (5/10) were delivered to the arm. Results: The temperature required to obtain a moderate pain intensity rating was not significantly different between the two groups (high N (mean ± SD): 43.92±1.44, mean low 44.25±1.14, p > 0.5). Preliminary fMRI data analysis suggests that, despite no difference in noxious input, high N is associated with more activity in the rACC, mPFC, left IFG and left DLPFC during pain perception, compared to low N. Conclusions: These preliminary results suggest that areas involved in emotion processing and regulation are more activated in young, healthy volunteers with high Neuroticism. An alteration in the function of pathways used for emotion and pain regulation, could explain why a population at risk for depression is also at risk for chronic pain, and hint towards the mechanisms involved in this risk.