[The new Parkinson's disease pain classification system (PD-PCS)]. / Die neue Parkinson-Schmerzklassifikation (PSK).

BACKGROUND: Chronic pain is a common non-motor symptom in patients with Parkinson's disease (PD). AIM: To facilitate the diagnosis of pain in PD, we developed a new classification system the Parkinson's disease pain classification system (PD-PCS) and translated the corresponding validated questionnaire into German. METHODS: A causal relationship of the respective pain syndrome with PD can be determined by four questions before assigning it hierarchically into one of three pain categories (neuropathic, nociceptive and nociplastic). RESULTS: In the initial validation study 77% of the patients (122/159) had PD-associated pain comprising 87 (55%) with nociceptive, 36 (22%) with nociplastic and 24 (16%) with neuropathic pain. The study revealed a high validity of the questionnaire and a moderate intrarater and interrater reliability. The questionnaire has been adapted into German and employed in 30 patients. DISCUSSION: The PD-PCS questionnaire is a valid and reliable tool to determine the relationship of a pain syndrome with PD before classifying it according to the underlying category, facilitating further diagnostics and treatment.

Neuropathic pain in rheumatoid arthritis and its association with Afro-descendant ethnicity: a hierarchical analysis.

BACKGROUND: nociceptive pain from joint damage caused by autoimmune inflammatory disease is expected in rheumatoid arthritis. However, neuropathic pain also occurs and persists even with the disease under control. This study aimed to investigate factors associated with neuropathic pain in rheumatoid arthritis by considering sociodemographic and behavioral data as well as lifestyle and clinical aspects in a self-referenced afro-descendant ethnicity sample. METHODS: In a cross-sectional study, the Douleur Neuropathique 4, Health Assessment Questionnaire, the Hospital Anxiety and Depression Scale and sociodemographic characteristics were used. Additionally, a Bivariate analysis was performed, followed by hierarchical multiple logistic regression, with results expressed as odds ratio and 95% confidence intervals. RESULTS: the frequency of NP was at a proximal level consisting of clinical characteristics related to anxiety (p=0.03) and depression (p=0.04). When a hierarchical multiple logistic regression analysis was conducted, an independent association was identified between neuropathic pain and black race. At the third and fourth stages, when the clinical variables were adjusted by race, an association was found with moderate functionality (p=0.04) and anxiety (p=0.04). CONCLUSION: neuropathic pain in rheumatoid arthritis is related to the Afro-descendant ethnicity that affects functionality and anxiety levels.

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

BACKGROUND: 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. METHODS: This cross-sectional study aimed to describe non-motor symptoms in MND and their impact on quality of life and functional status, with a focus on pain and sensory changes. Eighty patients (31 females, 55.7 ± 12.9 years old) with MND underwent a neurological examination, pain, mood, catastrophizing and psychophysics assessments [quantitative sensory testing (QST) and conditioned pain modulation (CPM)], and were compared to sex- and age-matched healthy controls (HC). RESULTS: Chronic pain was present in 46% of patients (VAS =5.18 ± 2.0). Pain of musculoskeletal origin occurred in 40.5% and was mainly located in the head/neck (51%) and lower back (35%). Neuropathic pain was not present in this sample. Compared to HC, MND patients had a lower cold detection threshold (p < 0.002), and significantly lower CPM scores (4.9 ± 0.2% vs. 22.1 ± 0.2%, p = 0.012). QST/CPM results did not differ between MND patients with and without pain. Pain intensity was statistically correlated with anxiety, depression and catastrophism, and spasticity scores were inversely correlated with CPM (ρ = -0.30, p = 0.026). CONCLUSIONS: Pain is frequently reported by patients with MNDs. Somatosensory and CPM changes exist in MNDs and may be related to the neurodegenerative nature of the disease. Further studies should investigate the most appropriate treatment strategies for these patients. SIGNIFICANCE: We report a comprehensive evaluation of pain and sensory abnormalities in motor neuron disease (MND) patients. We assessed the different pain syndromes present in MND with validated tools, and described the QST and conditioned pain modulation profiles in a controlled design.

Restless legs syndrome in Wilson's disease: frequency, characteristics, and mimics.

OBJECTIVE: To determine characteristics, clinical significance, frequency, and mimics of restless legs syndrome (RLS) in a cohort of Wilson's disease (WD, n = 42/f = 18), compared to healthy, matched controls. MATERIALS AND METHODS: Structured clinical interviews (patients and caregiving family members), repeated neurological examinations (afternoon and presleep), comprehensive laboratory tests, WD-, RLS-, and sleep-specific rating scales, and video-polysomnography. RESULTS: Thirteen patients with WD (13/42 = 31.0%) clearly fulfilled the five diagnostic criteria of RLS; in eight patients (19.1%), the burden of RLS was clinically significant. The RLS was of moderate severity, equally distributed among sexes, manifested mainly in the evening and before falling asleep, and had developed mostly after clinical manifestation of WD (time elapsed 10.2 ± 14.5 years), still at a young mean age (27.5 ± 11.5 years). The known RLS-associated features were absent (normal iron and kidney parameters) or rare (positive family history, polyneuropathy). Compared to WD patients without RLS, patients with RLS were significantly elder and had suffered longer from WD. WD-specific RLS mimics as well as RLS confounding motor comorbidities (dystonia, tremor, chorea) were frequent and a diagnostic challenge; in difficult cases, the differentiation was reached by clinical observation of the motor behavior in the evening or at nighttime. CONCLUSION: RLS was frequent in this cohort of WD and might be causally related to WD. RLS should be included in the diagnostic work-up of WD. In complex motor disorders, differential diagnosis of RLS might require evening/nighttime examination and video-polysomnography. In WD patients with a clinically significant RLS, treatment with dopaminergic substances may be considered.

From pulses to pain relief: an update on the mechanisms of rTMS-induced analgesic effects.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that allows cortical stimulation. Recent studies have shown that rTMS of the primary motor cortex or dorsolateral prefrontal cortex decreases pain in various pain conditions. The aim of this review was to summarize the main characteristics of rTMS-induced analgesic effects and to analyse the current data on its mechanisms of action. DATABASES: Medline, PubMed and Web of Science were searched for studies on the analgesic effects and mechanisms of rTMS-induced analgesic effects. Studies on epidural motor cortex stimulation (EMCS) were also included when required, as several mechanisms of action are probably shared between both techniques. RESULTS: Stimulation site and stimulation parameters have a major impact on rTMS-related analgesic effects. Local cortical stimulation is able to elicit changes in the functioning of distant brain areas. These modifications outlast the duration of the rTMS session and probably involve LTP-like mechanisms via its influence on glutamatergic networks. Analgesic effects seem to be correlated to restoration of normal cortical excitability in chronic pain patients and depend on pain modulatory systems, in particular endogenous opioids. Dopamine, serotonin, norepinephrine and GABAergic circuitry may also be involved in its effects, as well as rostrocaudal projections. CONCLUSIONS: rTMS activates brain areas distant from the stimulation site. LTP-like mechanisms, dependence on endogenous opioids and increase in concentration of neurotransmitters (monoamines, GABA) have all been implicated in its analgesic effects, although more studies are needed to fill in the still existing gaps in the understanding of its mechanisms of action.

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.

Pain-related evoked potentials: a comparative study between electrical stimulation using a concentric planar electrode and laser stimulation using a CO2 laser.

OBJECTIVE: To compare the pain-related evoked potentials (PREPs) obtained by superficial electrical stimulation using a concentric planar electrode to those obtained by CO2 laser stimulation. METHODS: In 12 healthy subjects, PREPs, sympathetic skin reflexes (SSRs), motor reaction times (mRTs), and the conduction velocity (CV) of the recruited nerve fibres were assessed in response to electrical and laser stimulation. RESULTS: In response to superficial electrical stimulation, PREP latencies and mRTs were shorter, while PREP amplitude tended to be increased. By contrast, SSR amplitudes and latencies and estimated CVs of the stimulated nerve fibres did not differ between electrical and laser stimulation. Fifteen minutes after PREP recordings, the residual pain intensity and the degree of unpleasantness were higher for laser stimulation than for electrical stimulation. In addition, CO2 laser stimuli induced dyschromic spots on the skin. For these reasons, all subjects declared that they would prefer superficial electrical stimulation rather than CO2 laser stimulation if they had to perform PREPs again. CONCLUSIONS: The estimated CVs of the recruited nerve fibres and the localized pinprick sensation felt by the subjects suggest that small-diameter fibres in the A-delta range, conveying "first-pain" information, were stimulated in response to superficial electrical stimulation as for laser stimulation. Superficial electrical stimulation using a concentric planar electrode could be a valuable alternative to laser stimulation for assessing PREPs in the practice of clinical neurophysiology.

Analgesic effects of repetitive transcranial magnetic stimulation of the motor cortex in neuropathic pain: influence of theta burst stimulation priming.

BACKGROUND: 'Conventional' protocols of high-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to M1 can produce analgesia. Theta burst stimulation (TBS), a novel rTMS paradigm, is thought to produce greater changes in M1 excitability than 'conventional' protocols. After a preliminary experiment showing no analgesic effect of continuous or intermittent TBS trains (cTBS or iTBS) delivered to M1 as single procedures, we used TBS to prime a subsequent session of 'conventional' 10 Hz-rTMS. METHODS: In 14 patients with chronic refractory neuropathic pain, navigated rTMS was targeted over M1 hand region, contralateral to painful side. Analgesic effects were daily assessed on a visual analogue scale for the week after each 10 Hz-rTMS session, preceded or not by TBS priming. In an additional experiment, the effects on cortical excitability parameters provided by single- and paired-pulse TMS paradigms were studied. RESULTS: Pain level was reduced after any type of rTMS procedure compared to baseline, but iTBS priming produced greater analgesia than the other protocols. Regarding motor cortex excitability changes, the analgesic effects were associated with an increase in intracortical inhibition, whatever the type of stimulation, primed or non-primed. CONCLUSIONS: The present results show that the analgesic effects of 'conventional' 10 Hz-rTMS delivered to M1 can be enhanced by TBS priming, at least using iTBS. Interestingly, the application of cTBS and iTBS did not produce opposite modulations, unlike previously reported in other systems. It remains to be determined whether the interest of TBS priming is to generate a simple additive effect or a more specific process of cortical plasticity.

Spectrum of cognitive impairment in neurocysticercosis: differences according to disease phase.

OBJECTIVES: Cognitive decline related to neurocysticercosis (NC) remains poorly characterized and underdiagnosed. In a cross-sectional study with a prospective phase, we evaluated cognitive decline in patients with strictly calcified form (C-NC), the epidemiologically largest subgroup of NC, and investigated whether there is a spectrum of cognitive abnormalities in the disease. METHODS: Forty treatment-naive patients with C-NC aged 37.6 ± 11.3 years and fulfilling criteria for definitive C-NC were submitted to a comprehensive cognitive and functional evaluation and were compared with 40 patients with active NC (A-NC) and 40 healthy controls (HC) matched for age and education. Patients with dementia were reassessed after 24 months. RESULTS: Patients with C-NC presented 9.4 ± 3.1 altered test scores out of the 30 from the cognitive battery when compared to HC. No patient with C-NC had dementia and 10 patients (25%) presented cognitive impairment-no dementia (CIND). The A-NC group had 5 patients (12.5%) with dementia and 11 patients (27.5%) with CIND. On follow-up, 3 out of 5 patients with A-NC with dementia previously still presented cystic lesions with scolex on MRI and still had dementia. One patient died and the remaining patient no longer fulfilled criteria for either dementia or CIND, presenting exclusively calcified lesions on neuroimaging. CONCLUSIONS: Independently of its phase, NC leads to a spectrum of cognitive abnormalities, ranging from impairment in a single domain, to CIND and, occasionally, to dementia. These findings are more conspicuous during active vesicular phase and less prominent in calcified stages.

Antimicrobial activity of two techniques for arm skin disinfection of blood donors in Brazil.

OBJECTIVE: Evaluation of the antimicrobial effect of skin disinfection techniques is essential to avoid the transmission of infectious agents during blood transfusion. The aim of this study was to examine the effectiveness of two methods of arm skin disinfection used in blood donors at a Hemotherapy Center in Brazil that represents an important centre for distributing haemocomponents to many cities in the country. METHODS: Two skin disinfection techniques in 50 blood donors were evaluated. For the first arm, 10% povidone-iodine/two-stage technique was used. On the opposite arm, 0.5% chlorhexidine digluconate alcohol solution/one-stage technique was used. The swabs were seeded on three culture media: blood agar, mannitol salt agar and Mac Conkey agar. Automated bacterial classification based on biochemical tests/specific substrates was performed. Donor characteristics were collected using the computerised system of the Hemotherapy Center. RESULTS: We found that microbial reduction was significantly higher for 10% povidone-iodine technique (98.57-98.87%) when compared with 0.5% chlorhexidine technique (94.38-95.06%). The species Leuconostoc mesenteroides and Staphylococcus hominis showed resistance to both disinfection techniques. We did not find statistically significant relationships between donor characteristics and microbial reduction. CONCLUSIONS: Arm skin disinfection with 10% povidone-iodine produced better antimicrobial activity. We must acknowledge that 10% povidone-iodine technique has the limitation of being a two-stage method. However, prevention of adverse events due to bacterial contamination and transfusion reactions should be prioritised. Production of hypoallergenic and stronger antiseptics that allowed a safe one-stage disinfection technique should be encouraged in health systems, not only in Brazil but also around the world.

Cognitive impairment and dementia in neurocysticercosis: a cross-sectional controlled study.

OBJECTIVES: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, affecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of patients with NCYST in comparison with cognitively healthy controls (HC) and patients with cryptogenic epilepsy (CE). METHODS: Forty treatment-naive patients with NCYST, aged 39.25 +/- 10.50 years and fulfilling absolute criteria for definitive active NCYST on MRI, were submitted to a comprehensive cognitive and functional evaluation and were compared with 49 HC and 28 patients with CE of similar age, educational level, and seizure frequency. RESULTS: Patients with NCYST displayed significant impairment in executive functions, verbal and nonverbal memory, constructive praxis, and verbal fluency when compared with HC (p < 0.05). Dementia was diagnosed in 12.5% patients with NCYST according to DSM-IV criteria. When compared with patients with CE, patients with NCYST presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatial orientation. No correlation emerged between cognitive scores and number, localization, or type of NCYST lesions on MRI. CONCLUSIONS: Cognitive impairment was ubiquitous in this sample of patients with active neurocysticercosis (NCYST). Antiepileptic drug use and seizure frequency could not account for these features. Dementia was present in a significant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in world public health.

Neurophysiological comparison between the Sit-to-Stand test with the 6-Minute Walk test in individuals with COPD.

OBJECTIVES: The Sit-to-Stand test (SST) is accepted and utilized during functional assessments of COPD patients, along with the 6-Minute Walk test (6MWT). Since there is a lack of evidence in literature regarding the neurophysiological effectiveness of SST compared to 6MWT, the present study is justified with the purpose of assessing the neurophysiological effectiveness of SST in comparison to the 6MWT during the functional assessment of such patients, once it is known that both tests are good predictors of functional state. METHODS: Fourteen patients with moderate to severe COPD randomly performed the 6MWT and the SST with a 30-minute interval in between tests. Blood lactate was collected along with the median frequency (MDF), obtained with the electromyography of the muscles rectusfemoris (RF), vastus lateralis (VL), tibialis anterior (TA), and soleus (SO) for the comparison of the neurophysiological effectiveness. RESULTS: The results of the blood lactate concentration during rest and at the end of the functional tasks along with the results from the angular coefficient (AC) obtained from the median frequency were analyzed with the Student t test. The initial and final values obtained from SST and 6MWT were compared within each activity, along with the comparison between the initial and final values for each functional test. A significant difference (p = 0.0005) was only verified between the initial and final values of SST. CONCLUSION: We found neurophysiological correlation between both tests which enabled us to suggest that SST may determine functional status as easily as the 6MWT in regard to neurophysiological effectiveness.

A reappraisal of the value of lateral spread response monitoring in the treatment of hemifacial spasm by microvascular decompression.

BACKGROUND: Lateral spread response (LSR) to the electrical stimulation of a facial nerve branch is a specific electrophysiological feature of primary hemifacial spasm (HFS). The curative treatment of HFS is based on surgical microvascular decompression (MVD). However, the outcome of this procedure is not always satisfactory. OBJECTIVE: To evaluate the correlation between intraoperative LSR changes and the short- and long-term postoperative clinical outcome following MVD. METHODS: Thirty-two consecutive patients with primary HFS treated by MVD performed with intraoperative LSR monitoring were retrospectively included. The patients were assessed for the presence of HFS and surgical complications at 1 day, 1 month and 6 months after surgery. The long-term clinical result was assessed between 1 and 10 years (mean 5.4 years) using a self-report questionnaire. RESULTS: Patients were divided into three groups based on intraoperative LSR changes: (1) in 15 patients, LSRs were present before incision and disappeared after MVD (47%); (2) in nine patients, LSRs were present before incision but persisted despite MVD (28%); (3) in eight patients, LSRs were absent before surgery and remained so after the procedure (25%). Intraoperative LSR abolition during the MVD procedure correlated with HFS relief in the long term (p<0.0001, Fisher exact test), but not on the first day after surgery (p = 0.3564). CONCLUSIONS: Monitoring MVD by recording LSRs intraoperatively could be of value not only to indicate the resolution of the vasculonervous conflict at the end of surgery, but also to predict a successful clinical outcome in the long term after the surgical intervention.