Role of calcitonin gene-related peptide and substance P in different models of pain.

Calcitonin gene-related peptide (CGRP) and substance P (SP) play an important role in the development of pain and hyperalgesia. Experimental models have demonstrated that nitroglycerin (NTG)--a nitric oxide donor--provokes a hyperalgesic state, probably via the activation of second-order neurons in the nucleus trigeminalis caudalis. In order to gain further insight into the role of CGRP and SP in different types of experimental pain, we evaluated and compared changes in immunoreactivity (-ir) for these two neuropeptides at different levels of the central nervous system [nucleus trigeminalis caudalis (NTC) and dorsal horns of the lumbar spinal cord] in two animal models of hyperalgesia: systemic NTG administration and formalin test. Following NTG administration, CGRP-ir decreased steadily in the NTC, whereas SP-ir increased transiently. In the lumbar dorsal horns, NTG induced a decrease in SP-ir 1 h after its administration. Formalin injection induced an ipsilateral increase in both CGRP and SP immunostaining at 1 and 2 h in the lumbar dorsal horns. In the NTC, a significant decrease in CGRP-ir was observed at 1 h. The changes in the staining intensities were paralleled by changes in the numbers of CGRP and of SP varicosities in both the NTC and the lumbar dorsal horns. These findings show specific changes in CGRP and SP at different levels of the central nervous system in the different models of pain. In the case of the formalin test, the changes involve both neuropeptides synchronously and to the same extent, whereas in the case of NTG administration, CGRP seems to play a more prevalent and long-lasting role, particularly at the NTC level.

Combination of dexamethasone and etanercept reduces secondary damage in experimental spinal cord trauma.

The aim of our study was to evaluate the therapeutic efficacy of combination therapy with etanercept and dexamethasone (DEX) in vivo in experimental murine model of spinal cord trauma, which was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and cytokine production followed by recruitment of other inflammatory cells, production of inflammation mediators, tissue damage, apoptosis and disease. Treatment of the mice with etanercept (1.25 mg/kg) and DEX (0.025 mg/kg) when administered as a combination therapy but not as a single treatment significantly reduced the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) infiltration of neutrophils (MPO evaluation), (3) inducible nitric oxide synthase, nitrotyrosine, and cytokines expression (tumor necrosis factor-alpha and interleukin-1 beta), (4) and apoptosis (Terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, Fas-ligand expression and Bax and Bcl-2 expression). In a separate set of experiments we have also clearly demonstrated that the combination therapy significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate for the first time that strategies targeting multiple proinflammatory pathways may be more effective than a single effector molecule for the treatment of spinal cord trauma.

Intrathecal baclofen therapy in patients with severe spasticity.

Spasticity has been described as "a motor disorder, characterized by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflex as one component of the upper motor neuron syndrome". In patients with complete spinal cord lesions, severe untreatable spasticity can make movement, sitting and hygiene difficult or impossible while it may alter gait and personal care in patients with partial lesions. From a clinical point of view, it is useful to distinguish spinal cord spasticity from supraspinal spasticity. Traditionally, the Ashworth scale is the most widely used to quantify the tone of single muscles. In order to quantify hypereflexia, the Reflex Scale is also used. In the spinal spasticity which is characterized by spasms, the Spasm Frequency Scale is useful in order to monitor their frequency. Initially, management of spasticity is based on non-invasive treatments that later become more invasive. The first approach. the conservative treatment, usually includes elimination of the nociceptive stimuli, rehabilitative therapy (physical and occupational), orthopaedic prostheses and plaster corsets. These treatments, do not resolve spasticity in about 33% of cases. In these severe cases, more invasive procedures such as muscle infiltrations with botulin toxin and intrathecal baclofen infusion can be used.

Enhanced spasticity in primary progressive MS patients treated with interferon beta-1b.

Spasticity is a disabling symptom of MS that is enhanced during interferon beta-lb (IFNbeta-1b) treatment. Nineteen patients with primary progressive MS were treated with IFNbeta-1b; an additional 19 patients did not receive this treatment. Thirteen of the 19 patients treated with IFNbeta-1b had increased spasticity requiring increased antispasticity drug administration. This observation suggests that further studies are needed before interferons can be so widely used in primary progressive MS patients.

An unusual spinal presentation of Whipple disease.

SUMMARY: When Whipple disease (WD) is confined to the CNS, diagnosis may be difficult. We report a case of WD with spinal presentation in an otherwise healthy woman who had a 5-year history of relapsing-remitting cervico-thoracic myelopathy. We suggest that the diagnosis of WD should be considered in the presence of an enlarged and enhancing spinal cord even in the absence of any systemic involvement.

Topographical disorientation consequent to amnesia of spatial location in a patient with right parahippocampal damage.

We describe a patient who selectively lost the ability to orient himself in the environment after a stroke involving the right parahippocampal gyrus. The neuropsychological assessment showed a specific pattern of impairment of topographical memory; the patient recognised and recalled environmental landmarks but was unable to recall their spatial location. This study provides evidence that different forms of topographical disorientation may be related to distinct mechanisms of cognitive dysfunction. Furthermore, neuroimaging data suggest that a lesion of the right parahippocampal gyrus is critically related to pure topographical disorientation.

Reproducibility of normal facial motor nerve conduction studies and their relevance in the electrophysiological assessment of peripheral facial paralysis.

To determine the intra-examiner intertrial reproducibility of normal facial motor nerve conduction studies (FNCS) and their relevance in electrophysiological assessments of peripheral facial paralysis, 52 patients with acute unilateral Bell's palsy were examined on two separate occasions 1 months apart. Three electroneurographic methods were assessed. On the unaffected side of the face, FNCS are reliable when performed by a single examiner over time. Nevertheless, compound muscle action potential (CMAP) baseline-to-peak and peak-to-peak amplitude showed a rather high intertrial variability. Reproducibility of the assessed surface electrode recording procedures was similar. Regarding the affected side, in patients with mild axonotmesis of the facial nerve variations of electroneurographic parameters 1 months apart fell within the range of normal intertrial variability. In patients with severe or moderate axonotmesis, the distal latency and the M wave amplitude variations showed significant intertrial variations. Reproducibility of FNCS appears to be similar to that found in limb motor nerves. Normal variability curtails the sensitivity of FNCS in detecting mild facial nerve axonotmesis, although this technique remains useful in severe cases.

The spasticity evaluation test (SeT): a pilot study.

This paper addresses the development of an apparatus designed to evaluate clinically the presence of spasticity affecting the elbow. The biomechanical contributions due to the lever-arm muscles and to the gravity force are accounted for using software algorithms that express gravity force and lever arm as functions of the elbow angle and are able to provide information on the force exerted by the muscles at a known speed. The preliminary data indicate that the device can be applied easily in the clinical setting. Further studies are required to demonstrate conclusively the validity and reliability of this device in quantifying spasticity at the elbow.

R3 nociceptive reflex in multiple sclerosis patients with paroxysmal symptoms treated with gabapentin.

Gabapentin (GBP) is a new, well-tolerated antiepileptic drug found to be effective for painful paroxysmal symptoms (PS) in multiple sclerosis (MS). The aim of this study was to obtain a neurophysiological evaluation of the effects of GBP on the nociceptive system of MS patients suffering PS. We studied 10 MS patients, 6 males, 4 females (mean age 47.3 years), suffering PS (3 had trigeminal neuralgia, 1 painful tonic spasms and 6 dysesthetic or paresthetic symptoms). Three patients were, at the same time, also being treated with carbamazepine. Pain was evaluated by means of the Visual Faces Scale. R3 nociceptive reflex was recorded after 2 weeks' treatment. R3 thresholds and latencies were evaluated and a statistical analysis was performed. A significant variation was found in R3 thresholds between the values recorded before and during GBP treatment; no significant variation was observed in R3 latencies.

Pallidotomy improves quality of life in selected parkinsonian patients: an Italian report.

Pallidotomy has recently been reconfirmed as effective for otherwise intractable symptoms of Parkinson's disease. Nonetheless almost every aspect of its performance requires choices which are not fully established and may vary between centers. These include: 1) patient selection; 2) choice of imaging modality, 3) choice of anatomic landmarks for targeting the lesion, 4) choice of method for physiologic confirmation of location, 5) choice of lesion size and shape. We present two cases of pallidotomy procedures in Parkinsonian patients that in our knowledge are the first reported in Italy. Our experience and a careful review of the literature led to the following choices: 1) selection of Parkinsonian patients with dominant L-Dopa induced dyskinesia, akinetic and rigidity symptoms, 2) use of CT due to the distortion effects of MRI, 3) use of standard (Laitinen) coordinates combined with an image fusion method using MRI, 4) use of stimulation to gauge distance to internal capsule and optic tract, 5) production of vertical lesion covering internal segment of pallidum. At a 1-year follow-up the results include a 45% drop in UPDRS (Unified Parkinson's Disease Rating Scale) motor score and almost complete resolution of contralateral dopa induced dyskinesias in both patients.

Nociceptive R3 reflex in relapsing-remitting multiple sclerosis patients.

Pain in multiple sclerosis (MS) patients has only recently been recognised as a genuine symptom of this disease. It is important to determine whether this pain is the consequence of another symptom of MS or whether it is due to a demyelinating lesion affecting pain pathways. A close relationship has been found between the R3 component of the blink reflex and the pain threshold. The aim of this work was to carry out an objective evaluation of the nociceptive system in MS patients by means of the R3 component of the blink reflex. The study was performed on 20 healthy volunteers and on 20 clinically defined relapsing-remitting MS patients with EDSS not > 3.5, normal R1 and R2 components of the blink-reflex, personal and family anamnesis negative for migraine and trigeminal neuralgia; the patients were not taking drugs at the time of the test. A significant difference was found, between healthy volunteers and patients, for R3 threshold, pain threshold and R3 latency.

Peripheral neuropathy in myotonic dystrophy: electrophysiological and clinical features.

Peripheral neuropathy was investigated in thirty-one patients with myotonic dystrophy (MyD) and sixteen relatives. Using standard electrophysiological criteria, a sensorimotor axonal peripheral neuropathy was found in 14 MyD cases (45%) and not in unaffected first-degree relatives. The whole group of the MyD patients showed significant impairment of mean motor and sensory conduction values, compared with controls. The presence of polyneuropathy was correlated with the patients' age and the severity and duration of the clinical manifestations of MyD.

Electrically evoked long-latency responses in human forearm, arm and shoulder muscles.

Little is known about electrically evoked long-latency responses (LLR) in muscles other than hand muscles. We obtained LLR in forearm, arm and shoulder muscles by ipsilateral homonymous and heteronymous mixed and pure cutaneous electrical stimulation of the median or ulnar nerve in healthy subjects and in patients with focal unilateral Central Nervous System lesions. Our results point out the important role played by hand afferents in the sensorimotor coordination of multiarticulate upper limb movements.

[Electrophysiological findings after TRH-T administration to healthy volunteers]. / Rilievi elettrofisiologici dopo somministrazione di TRH-T in volontari sani.

The central effect of acutely and chronically administered TRH-T were evaluated in ten volunteers by analysis of spontaneous and evoked cerebral electric activity. None of the subjects showed significant BAER changes, of EEG abnormalities. In some subjects acute and chronic administration of TRH-T increased alfa and beta 1 activities.

[Patients with stroke treated with TRH-T. Evaluation of electric brain activity using traditional and computerized methods]. / Pazienti affetti da ictus cerebrale in trattamento con TRH-T. Valutazione dell'attività elettrica cerebrale con metodica tradizionale e computerizzata.

This study was aimed at evaluating the EEG effects of acutely and chronically administered protirelin tartrate in patients with acute and chronic cerebrovascular disease by traditional and computerized analysis of cerebral electric activity. Our data showed: a) TRH-T did not induce EEG abnormalities; b) acute and chronic administration of TRH-T increased alpha frequency band and decreased delta and theta activities.

[Peripheral neuropathy associated with Castleman's lymphoma]. / Neuropatia periferica associata a linfoma di Castleman.

Castleman's lymphoma is a rare clinicopathological entity and is often difficult to classify nosographically. From the histopathological point of view two variants are recognized, one hyalino-vascular and one plasma cellular. Moreover Castleman's lymphoma may be multifocal or unifocal (located within the thorax in 70% of patients). The plasma cellular variant is often associated with systemic symptoms such as fever, sweating, organomegaly, polyneuropathy, and mono- or polyclonal gammopathy. We describe a rare case of unifocal, plasma cellular-type Castleman's lymphoma located in the mediastinum, asymptomatic at onset but later dominated by neurological symptoms (chronic isolated polyneuropathy whose clinical expression was predominantly motor). A brief review is presented of the main clinico-histological characteristics of Castleman's lymphoma together with some hypotheses about the pathogenesis of the associated neuropathy.

[Polyneuropathies associated with lymphoplasmacytic dyscrasias: the clinical and instrumental characteristics of a 38-patient case load]. / Polineuropatie associate a discrasie linfoplasmacellulari: caratteristiche cliniche e strumentali di una casistica di 38 pazienti.

A varying percentage from 40 to 60% of patients having lymphoplasmacytic dyscrasias with a monoclonal component shows a clinical or subclinical polyneuropathy. From a different viewpoint, a monoclonal gammopathy has been detected in 10% of patients effected by chronic idiopathic polyneuropathy. A case study of 38 patients with lymphoplasmacytic dyscrasia subjected to clinical, immunohematological and electrophysiological examination revealed a high prevalence of polyneuropathy (84%), mainly axonal (72%) and often subclinical. The neuropathy was evenly distributed between patients having malignant and benign lymphoplasmacytic dyscrasias. No statistically significant correlation was found between the presence of neuropathy and the main clinical and immunohematological data. This supports the concept that the pathogenesis of polyneuropathy associated with lymphoplasmacytic dyscrasias may be multifactorial. Nor can it be ruled out that the paraprotein may in fact be secondary to the polyneuropathy or sometimes a simple coincidence.