Clinical criteria and diagnostic assessment of fibromyalgia: position statement of the Italian Society of Neurology-Neuropathic Pain Study Group.

BACKGROUND: The role of central and/or peripheral nervous system dysfunction is basically fundamental in fibromyalgia. AIM: The aim of this position statement on behalf of the Neuropathic Pain Study Group of the Italian Society of Neurology is to give practical guidelines for the clinical and instrumental assessment of fibromyalgia (FM) in the neurological clinical practice, taking into consideration recent studies. METHODS: Criteria for study selection and consideration were original studies, case-controls design, use of standardized methodologies for clinical practice, and FM diagnosis with ACR criteria (2010, 2011, 2016). RESULTS: ACR criteria were revised. For diagnostic procedure of small-fiber pathology, 47 studies were totally considered. Recent diagnostic criteria should be applied (ACR, 2016). A rheumatologic visit seems mandatory. The involvement of small fibers should request at least 2 among HRV + SSR and/or laser-evoked responses and/or skin biopsy and/or corneal confocal microscopy, eventually followed by monitoring of metabolic and/or immunological/ and or/paraneoplastic basis, to be repeated at 1-year follow-up. CONCLUSIONS: The correct diagnostic approach to FM could promote the exclusion of the known causes of small-fiber impairment. The research toward common genetic factors would be useful to promote a more specific therapeutic approach.

Pain and agitation treatment in severe dementia patients: The need for Italian Mobilization-Observation-Behavior-Intensity-Dementia (I-MOBID2) pain scale translation, adaptation and validation with psychometric testing.

The 97% of dementia patients develops fluctuant neuropsychiatric symptoms often related to under-diagnosed and unrelieved pain. Up to 80% severe demented nursing home residents experiences chronic pain due to age-related comorbidities. Patients lacking self-report skills risk not to be appropriately treated for pain. Mobilization-Observation-Behavior-Intensity-Dementia (MOBID2) is the sole pain scale to consider the frequent co-occurrence of musculoskeletal and visceral pain and to unravel concealed pain through active guided movements. Accordingly, the Italian real-world setting can benefit from its translation and validation. This clinical study provides a translated, adapted and validated version of the MOBID2, the Italian I-MOBID2. The translation, adaptation and validation of the scale for non-verbal, severe demented patients was conducted according to current guidelines in a cohort of 11 patients over 65 with mini-mental state examination ≤ 12. The I-MOBID2 proves: good face and scale content validity index (0.89); reliable internal consistency (Cronbach's α = 0.751); good to excellent inter-rater (Intraclass correlation coefficient, and test-retest (ICC = 0.902) reliability. The construct validity is high (Rho = 0.748 p < 0.05 for 11 patients, Spearman rank order correlation of the overall pain intensity score with the maximum item score of I-MOBID2 Part 1; rho=0.895 p < 0.01 for 11 patients, for the overall pain intensity score with the maximum item score of I-MOBID2 Part 2) and a good rate of inter-rater and test-retest agreement was demonstrated by Cohen's K = 0.744. The average execution time is of 5.8 min, thus making I-MOBID2 a useful tool suitable also for future development in community setting with administration by caregivers.

High-resolution ultrasound in the diagnosis of failed carpal tunnel decompression: a study of 35 cases.

We used high-resolution ultrasound to examine 35 median nerves (35 patients) with failed carpal tunnel decompression to identify the cause of failure. The carpal tunnel was examined before revision surgery, and the results were correlated with surgical findings. The cross-sectional area was measured, and nerve morphology was analysed at the sites of compression. We found persistent median nerve compression in 30 out of 35 patients. In 20 patients, the compression was caused by a residual transverse carpal ligament, in four by perineural fibrosis, in five by both of these causes and in one by tenosynovitis. In four patients, evidence of median nerve injury with an epineural/fascicular lesion was detected; and in one, no abnormalities were found. Surgical findings were consistent with the ultrasound findings except in one patient where tenosynovitis was associated with a giant cell tumour, which was missed by ultrasound. High-resolution ultrasound can provide helpful information in preoperative diagnosis of failed carpal tunnel decompression with good correlation between the ultrasound and surgical findings.Level of evidence: IV.

A Delphi consensus statement of the Neuropathic Pain Special Interest Group of the Italian Neurological Society on pharmacoresistant neuropathic pain.

To improve patient care and help clinical research, the Neuropathic Pain Special Interest Group of the Italian Neurological Society appointed a task force to elaborate a consensus statement on pharmacoresistant neuropathic pain. The task force included 19 experts in neuropathic pain. These experts participated in a Delphi survey consisting of three consecutive rounds of questions and a face-to-face meeting, designed to achieve a consensus definition of pharmacoresistant neuropathic pain. In the three rounds of questions, the participants identified and described the main distinguishing features of pharmacoresistance. In the face-to-face meeting the participants discussed the clinical features determining pharmacoresistance. They finally agreed that neuropathic pain is pharmacoresistant when "the patient does not reach the 50% reduction of pain or an improvement of at least 2 points in the Patient Global Impression of Change, having used all drug classes indicated as first, second, or third line in the most recent and widely agreed international guidelines, for at least 1 month after titration to the highest tolerable dose." Our consensus statement might be useful for identifying eligible patients for invasive treatments, and selecting patients in pharmacological trials, thus improving patient care and helping clinical research.

Effects of a nutraceutical combination in patients with chronic lumbosacral radicular pain.

Drugs used for the treatment of chronic lumbosacral radicular pain (LRP) may have frequent adverse effects leading to medication withdrawal. The use of add-on nutraceuticals, which have no side effects, may therefore play a role in LRP treatment. We performed a six-week, single-center, open label prospective uncontrolled clinical study to evaluate the effect of a nutraceutical combination (Noxiall®) used as an add-on therapy in patients with chronic LRP. Fifteen patients were treated with Noxiall® twice a day for 10 consecutive days, followed by once-daily administration up to the end of the six-week treatment. The participants were evaluated at two visits (before-after), when primary and secondary outcomes were assessed. We found a significant reduction in pain severity post-treatment, as assessed using a numerical rating scale (p= 0.03), and a significant reduction in painkiller intake (p=0.03). Nutraceuticals could be a complementary therapy for chronic LRP.

Electrodiagnostic and nerve ultrasonographic features in upper limb spasticity: an observational study.

To better understand the effects of spasticity on peripheral nerves, we evaluated the electrodiagnostic and nerve ultrasonographic features of the median and ulnar nerves in adults with upper limb spasticity. Twenty chronic stroke patients with spastic hemiparesis underwent nerve conduction study and nerve ultrasonography of the median and ulnar nerves at both upper limbs. Affected versus unaffected upper limb comparisons showed significant differences in the median and ulnar nerve distal motor latencies, compound muscle action potentials and F-wave minimal latencies. Furthermore, we observed a significantly greater median nerve crosssectional area at the elbow of the affected upper limb compared with the unaffected one. Our findings confirmed electrodiagnostic asymmetries and nerve ultrasonographic abnormalities in the affected versus the unaffected upper limb after stroke. Slight changes in lower motor neuron activity and spasticity might contribute to these alterations.

Pisa syndrome in Parkinson's disease: electromyographic quantification of paraspinal and non-paraspinal muscle activity.

Patients with Parkinson's disease (PD) and Pisa syndrome (PS) may present tonic dystonic or compensatory (i.e. acting against gravity) hyperactivity in the paraspinal and non-paraspinal muscles. Electromyographic (EMG) activity was measured in nine patients with PD and PS, three with PD without PS, and five healthy controls. Fine-wire intramuscular electrodes were inserted bilaterally into the iliocostalis lumborum (ICL), iliocostalis thoracis (ICT), gluteus medius (GM), and external oblique (EO) muscles. The root mean square (RMS) of the EMG signal was calculated and normalized for each muscle. In stance condition, side-to-side muscle activity comparisons showed a higher RMS only for the contralateral ICL in PD patients with PS (p=0.028). Moreover, with increasing degrees of lateral flexion, the activity of the EO and the ICL muscles progressively increased and decreased, respectively. The present data suggest that contralateral paraspinal muscle activity plays a crucial compensatory role and can be dysfunctional in PD patients with PS.

How to diagnose neuropathic pain? The contribution from clinical examination, pain questionnaires and diagnostic tests.

Patients with peripheral and central nervous system diseases may suffer from different types of pain, namely nociceptive, neuropathic and mixed pain. Although in some cases, the distinction between these types of pain is clinically evident, yet in some patients an accurate differential diagnosis requires dedicated clinical examination, screening questionnaires and diagnostic techniques some of which are available only in specialized pain centres. This review briefly addresses the currently agreed definitions of the different types of pain and shows how clinical examination, pain questionnaires and diagnostic tests can help the clinicians in identifying neuropathic pain.

Topical distribution of initial paresis of the limbs to predict clinically relevant spasticity after ischemic stroke: a retrospective cohort study.

BACKGROUND: The degree of initial paresis relates to spasticity development in stroke patients. However, the importance of proximal and distal paresis in predicting spasticity after stroke is unclear. AIM: To investigate the role of topical distribution of initial limb paresis to predict clinically relevant spasticity in adults with stroke. DESIGN: Retrospective cohort study METHODS: Seventy-two first-ever ischemic stroke patients were examined. At the acute phase of illness, demographics and the European Stroke Scale motor items (maintenance of outstretched arm position, arm raising, wrist extension, grip strength, maintenance of outstretched leg position, leg flexion, foot dorsiflexion) were evaluated. At six months after the stroke onset, spasticity was assessed at the upper and lower limb with the modified Ashworth Scale. Clinically relevant spasticity was defined as modified Ashworth Scale ≥3 (0-5). RESULTS: The degree of initial paresis of the proximal muscles of the upper limb and the distal muscles of the lower limb showed the strongest association and the best profile of sensitivity-specificity in predicting clinically relevant spasticity at the upper and lower limb, respectively. Younger age showed higher risk for developing clinically relevant spasticity in the upper limb. CONCLUSIONS: Our findings support the hypothesis that the initial degree of proximal paresis of the upper limb and distal paresis of the lower limb as well as age may be considered early predictors of clinically relevant spasticity in adults with ischemic stroke. CLINICAL REHABILITATION IMPACT: Our findings further improve the role of initial paresis as predictor of spasticity after stroke.

Pain and motor function in carpal tunnel syndrome: a clinical, neurophysiological and psychophysical study.

OBJECTIVE: Patients with carpal tunnel syndrome (CTS) complain of motor symptoms. The study is aimed to understand which features are associated with the presence of motor symptoms in CTS. METHODS: We recruited 282 consecutive CTS patients. After selection, 129 patients (203 hands) were included. Patients were asked about the presence and severity of hand weakness (HW) and hand clumsiness (HC). They underwent a self-administered questionnaire on symptoms, clinical evaluation and neurographic study. Quantitative sensory testing (QST) was performed on the patients with unilateral right CTS. RESULTS: HW and HC may be found in 56 % and 48 % of CTS hands, respectively. HW was related to the severity of sensory symptoms (pain, numbness and tingling) but not to clinical-neurographic measures of median nerve involvement. HC was related to the severity of sensory symptoms and to the clinical-neurographic signs of motor but not sensory nerve damage. Motor symptoms were significantly more frequent in right hands. QST showed a relationship between the presence and severity of HW and HC and the warm threshold. CONCLUSIONS: Motor symptoms may be found in approximately half of CTS hands. Clinical and neurographic signs of median nerve motor damage appear to be poorly correlated to motor symptoms. The factor that can help reconcile the discrepancy between motor symptoms and motor signs is pain. Pain modulation on motor function may take place at various anatomical levels in CTS. Nociceptive C-fibers may be involved in pain-motor interactions finally leading to motor symptoms.

Cutaneomotor integration in human hand motor areas: somatotopic effect and interaction of afferents.

The aim of this study was to elucidate sensorimotor integration in human hand motor areas, its time course, somatotopy and the interaction of sensory fields arising from two different fingers. We studied the influence of different intensities of electrical digital stimulation of two different fingers on motor-evoked potentials elicited in hand muscles by transcranial magnetic stimulation (TMS). Single conditioning electrical stimuli were applied to the right second (D2) and fifth fingers (D5) individually and also to both fingers (D2+D5) simultaneously in six normal volunteers. Magnetic tests, adjusted to produce a response in the abductor digiti minimi muscle of the right hand, were delivered using a circular and a focal coil. The digital stimuli were delivered to the finger at the sensory threshold (ST), at 3 and 5 times the ST, and over the pain threshold at interstimulus intervals (ISIs) ranging from 10 to 100 ms. In order to define the anatomical level of the sensorimotor interactions, the effect of the digital stimulation on TMS was compared to the effect on transcranial electrical stimulation. When the peripheral stimulation was delivered at the ST a small inhibitory effect was found only when stimulating both fingers. At 3 times the ST we detected a topographic distribution of motor-evoked potential inhibition, which partially disappeared at higher intensity (5 times the ST); two types of convergence effects took place at different ISIs. When conditioning stimuli were painful, somatotopy and convergence were lost. Sensorimotor integration shows somatotopy and interaction of afferents at different sites. The intensity of the conditioning stimulus plays an important role in topography and sensory convergence. The importance of these mechanisms in physiology and physiopathology is discussed.

Hyperexcitable cortical responses in progressive myoclonic epilepsy: a TMS study.

OBJECTIVE: Transcranial magnetic stimulation (TMS) has allowed investigators to study intracortical inhibition and facilitation and sensorimotor integration in motor disorders and epilepsy. The authors used TMS to elucidate the pathophysiology of reflex myoclonus with giant somatosensory evoked potentials (SEP). METHODS: The authors studied four patients with progressive myoclonic epilepsy. All patients had giant SEP elicited by mixed and digital nerve stimulation. They studied the response to paired-pulse TMS at interstimulus intervals (ISI) ranging from 1 to 15 ms and the conditioning effect of digital electrical stimulation at ISI ranging from 10 to 100 ms on the motor evoked potential amplitude to TMS. RESULTS: Digital stimulation markedly facilitated conditioned motor evoked potentials at ISI ranging from 25 to 40 ms in all patients. This pattern was significantly different from the inhibition observed in controls (n = 12) at the same ISI. In the patients, paired-pulse TMS showed a decrease in intracortical inhibition in the motor cortex in comparison with controls. CONCLUSIONS: These findings suggest cortical and subcortical components of abnormal sensorimotor integration in addition to hyperexcitability of the sensory and motor cortex in our myoclonic patients.

Transient inhibition of the human motor cortex by capsaicin-induced pain. A study with transcranial magnetic stimulation.

Motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the left motor cortex were recorded from the right first dorsal interosseous (FDI), abductor pollicis brevis (APB), abductor digiti minimi (ADM), flexor carpi radialis (FCR), extensor carpi radialis (ECR) in 17 normal subjects, before and after painful application of capsaicin on the skin overlying the right FDI and FCR muscles. The amplitude of MEPs from the FDI and FCR was significantly reduced from 20 to 30 min after the application of capsaicin over the FDI and FCR muscles, respectively, then progressively returned to the basal values. A similar trend of MEPs inhibition was observed for APB and FCR muscles, but this reduction was not significant. Indices of peripheral nerve (M-wave) and spinal cord excitability (F and H waves) did not change throughout the experiments. Motor cortex inhibition induced by tonic cutaneous pain is maximal to muscles adjacent to the painful area. This inhibition may be due to the activation of the C fibres which mediate 'slow' nociception and might be important to alert subject to possible phasic nociceptive events that may occur close to the painful area.