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.

Consistence and discrepancy of neuropathic pain screening tools DN4 and ID-Pain.

Pain is a subjective condition that cannot be objectively measured; for this reason, self patient-perspective is crucial. Recently, several screening tools to discriminate between nociceptive and neuropathic pain have been developed. We aimed at assessing the consistence and discrepancy of two widely used screening tools, The Douleur Neuropathique 4 (DN4) and the 6-item questionnaire (ID-Pain), by comparing their ability in discriminating neuropathic from nociceptive pain. DN4 and ID-Pain were administered to 392 Italian patients attending 16 outpatient services for peripheral nerve diseases. Based on medical history, clinical findings and diagnostic tools, patients were divided into two groups (neuropathic and nociceptive). Globally, ID-Pain identified neuropathic pain in 60 % of patients (38 % probable, 22 % likely). Interestingly also DN4 diagnosed neuropathic pain in 60 % of cases. A discrepancy was observed in 16 % of cases. DN4 and ID-Pain resulted to be highly interrelated in the identification of neuropathic pain. Sensitivity of DN4 was 82 % and specificity was 81 %, while ID-Pain (considering both probable and likely groups) showed sensitivity 78 % and specificity 74 %. Reliable screening tools for neuropathic pain are well related between them; hence, they are available for researchers and clinicians who may choose the most appropriate for their activity. Since the gold standard for the diagnosis and treatment of neuropathic pain cannot do without a neurological evaluation, perhaps DN4, that includes physician objective measures, may help reducing the percentage of dubious cases. Conversely, when needing a more agile tool (not needing a physician) ID-Pain may be adopted.

High prevalence of neuropathies in patients with end-stage liver disease.

OBJECTIVES: Peripheral neuropathy has been reported in association with end-stage liver disease, but there is only a limited number of reports on the incidence and features of these neuropathies. MATERIALS AND METHODS: In this study, 83 patients awaiting liver transplantation were evaluated for the presence of peripheral and autonomic neuropathy. RESULTS: Sixty-five percent of the patients had evidence of neuropathy, in agreement with peripheral NCS or cardiovascular autonomic function test. The neuropathy was more frequent in patients with advanced hepatic failure, evaluated with the MELD score. The most frequent abnormalities in nerve conduction studies were sensory-motor neuropathies and sensory neuropathies, with a length-dependent pattern. CONCLUSION: Peripheral neuropathy and autonomic neuropathy are common in patients with end-stage liver disease with different etiology and correlate with the severity of the liver disease.

Chronic triventricular hydrocephalus: morphological and functional study before and after ventriculoperitoneal shunting.

We have neuroradiologically and neuropsycho-physiologically studied a case of chronic hydrocephalus due to congenital acqueductal stenosis, before and after ventriculoperitoneal shunting. The aims of the study were: 1) to point out the correlation between neuroimaging (Computerized Tomography/Magnetic Resonance Imaging) and mapping of Computerized Spectral Analysis EEG (CSA-EEG); 2) to monitor evoked bioelectrical activity by neurophysiological evaluation of acoustic and visual N1 and P3. Both bioelectrical activity and neuroimaging evaluation showed a considerable recovery of the neurobiological substratum after neurosurgical shunting, while neuropsychological investigation showed a slight improvement in all cognitive tasks.

Somatosensory- and motor-evoked potential monitoring during spine and spinal cord surgery.

STUDY DESIGN: Prospective, observational study. SETTING: Regional Trauma Center, Torino, Italy. OBJECTIVES: Complex spinal surgery carries a significant risk of neurological damage. The aim of this study is to determine the reliability and applicability of multimodality motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SEPs) monitoring during spine and spinal cord surgery in our institute. METHODS: Recordings of MEPs to multipulse transcranial electrical stimulation (TES) and cortical SEPs were made on 52 patients during spine and spinal cord surgery under propofol/fentanyl anaesthesia, without neuromuscular blockade. RESULTS: Combined MEPs and SEPs monitoring was successful in 38/52 patients (73.1%), whereas only MEPs from at least one of the target muscles were obtained in 12 patients (23.1%); both MEPs and SEPs were absent in two (3.8%). Significant intraoperative-evoked potential changes occurred in one or both modalities in five (10%) patients. Transitory changes were noted in two patients, whereas three had persistent changes, associated with new deficits or a worsening of the pre-existing neurological disabilities. When no postoperative changes in MEP or MEP/SEP modalities occurred, it was predictive of the absence of new motor deficits in all cases. CONCLUSION: Intraoperative combined SEP and MEP monitoring is a safe, reliable and sensitive method to detect and reduce intraoperative injury to the spinal cord. Therefore, the authors suggest that a combination of SEP/MEP techniques could be used routinely during complex spine and/or spinal cord surgery.

A further critical evaluation of requests for electrodiagnostic examinations.

The aim of this study was to evaluate the impact of electrophysiological (EDX) tests in the clinical management and diagnosis of patients, and the appropriateness of the referral diagnosis. A study was carried out in three electrodiagnostic services in the Torino area, over a 12-month period. In our study 3,900 individuals (2,340 females, 1,560 males) were evaluated. Patients underwent EDX examinations including nerve conduction study, electromyography and repetitive stimulation test. Most patients had been sent for EDX tests by specialists. Specialists suspected mainly polyneuropathy, whilst general practitioners suspected mainly carpal tunnel syndrome. Seventy-two percent of the requests were correctly formulated, 55% by general practitioners and 77% by specialists. There was a concordance between the results of the EDX tests and diagnostic hypothesis 40% of the time. This study confirms the usefulness and diagnostic impact of EDX examinations and evidences the amount of time and resources wasted as a result of incorrect or incomplete requests.

Pain affects the quality of life of neuropathic patients.

The aim of this study was to verify the extent to which the presence of pain affects the quality of life (QoL) of neuropathic patients. The patients were selected in our Department of Peripheral Nervous System Diseases. We enrolled 120 consecutive patients with chronic polyneuropathy who had not received continuous pain therapy during the two months preceding study entry, and administered them the Total Neuropathy Score (TNS), the official Italian version of the SF-36 and the Italian Pain Questionnaire (QUID). Our main finding was that the QoL is affected not only by the presence of neuropathy, but also by the presence and intensity of pain: the physical aspect of the QoL correlated only weakly with the TNS, but pain was closely related to a worsening in this parameter; moreover, the mental domains of the SF-36 were only correlated with pain. Pain per se worsens the QoL of neuropathic patients, regardless of disease severity.

Differential diagnosis of chronic dysimmune demyelinating polyneuropathies with and without anti-MAG antibodies.

The distinction between chronic demyelinating polyneuropathies associated with IgM paraproteinemia and anti-myelin-associated glycoprotein (MAG) antibodies (MAG-PN) and chronic inflammatory demyelinating polyneuropathies (CIDPs) relies on the anti-MAG antibodies assay. The aim of the study was to identify clinical and electrophysiological features suggesting a diagnosis of MAG-PN. Fourteen patients with MAG-PN and 35 with CIDP were included, and a discriminant analysis was performed to identify the clinical and electrophysiological features suggestive of MAG-PN. Pure sensory clinical phenotype, low median and ulnar terminal latency index, and absence of M responses in the lower limbs were significantly associated with the diagnosis of MAG-PN, and indicate a moderate to large increase in probability of this diagnosis in patients with chronic dysimmune demyelinating polyneuropathies.

Intracranial stimulation of the facial nerve: normative values with magnetic coil in 240 nerves.

This study was aimed at defining normative values of latency and amplitude of the compound muscle action potential (CMAP) from the orbicularis oculi muscle, obtained by transcranial magnetic stimulation. We evaluated the dependence of latency and amplitude on the age of the subjects, in order to calculate cut-off values for each age decade. A total of 120 healthy normal subjects, aged 15-78 years, were studied. CMAP from the orbicularis oculi muscle, pars inferior, was excited by means of transcranial magnetic stimulation of the homolateral scalp. A suitable mathematical model was developed to evaluate the mean variation of the latency and amplitude of CMAP for each age decade in the studied population. Mean values were, respectively, 4.62+/-0.40 ms for latency and 4.17+/-0.72 mV for amplitude. We found an increase in latency of about 0.12 ms for every ten years, that became 0.15 ms if referring only to subjects over 20 years, and a decrease in amplitude of 0.18 mV each ten years. Normality interval values for the latency and amplitude were calculated for each age decade. Our data, obtained in a representative population for range of age of evaluated subjects, provide normality values and variability coefficients useful for future confronting works.

Terminal latency index in polyneuropathy with IgM paraproteinemia and anti-MAG antibody.

Criteria for the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) are met by the polyneuropathy associated with immunoglobulin M (IgM) paraproteinemia and anti-myelin-associated glycoprotein (MAG) antibody (MAG-CIDP). However, MAG-CIDP differs from other types of CIDP, mainly in its poorer response to treatment. The utility of terminal latency index (TLI) as an electrophysiological marker for MAG-CIDP has been debated. In this study we confirmed its diagnostic usefulness and evaluated TLI threshold values for motor nerves investigated in routine nerve conduction studies. Median, ulnar, peroneal, and tibial TLIs of 11 subjects with MAG-CIDP, 18 with CIDP, and 76 healthy controls were compared, and threshold values for MAG-CIDP evaluated as the lowest value with a likelihood ratio higher than 10. Mean TLI values and TLIs of all but the peroneal nerve were significantly lower in MAG-CIDP. Median nerve TLI of 0.26 and ulnar nerve TLI of 0.33 were identified as the threshold TLI values for MAG-CIDP.

Thalidomide neuropathy: clinical, electrophysiological and neuroradiological features.

OBJECTIVE: Thalidomide is a promising therapy for multiple myeloma. Sensory neuropathy is a side effect of thalidomide and resulted to be partially reversible in 50% of cases, suggesting a sensory ganglionopathy. Spinal cord magnetic resonance imaging (MRI) was found to be useful in the diagnosis of sensory ganglionopathies and we use it to determine if thalidomide neuropathy has features of a ganglionopathy. MATERIAL AND METHODS: Six patients with multiple myeloma developed thalidomide-induced polyneuropathy. Nerve conduction studies, somatosensory-evoked potentials (SEPs) and cervical and dorsal spinal cord MRI were obtained in all. RESULTS: All patients had a sensory neuropathy, with clinical or electrophysiological abnormalities involving all four limbs. Spinal cord MRI showed high signal intensity in the posterior columns in only one patient, with abnormal central conduction time at SEPs. CONCLUSION: Our results suggest that thalidomide can induce either an axonal length-dependent neuropathy or, less frequently, a ganglionopathy.

Thalidomide sensory neurotoxicity: a clinical and neurophysiologic study.

The clinical and neurophysiologic data from 65 patients taking thalidomide were reviewed. Thalidomide sensory neurotoxicity was found to be cumulative dose dependent but occurs only when the total dose is relatively high (>20 g). The risk of developing sensory neuropathy is around 10% below this threshold but increases with higher doses.