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.

Asymmetric Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a heterogeneous disorder according to clinical, electrophysiological, immunologic and pathologic findings. It has usually been considered as an immune-mediated polyneuropathy clinically characterised by acute symmetric muscle weakness and areflexia. We describe a patient who, after a Campylobacter jejuni infection, developed an acute motor-sensory neuropathy with marked and persistent asymmetry of clinical and electrophysiological findings. He had a high titre of anti-GM1 IgG antibodies and cytoalbuminologic dissociation and was responsive to intravenous immunoglobulins. Investigations and three years of follow-up excluded mimics of GBS. Tendon areflexia has recently been challenged as a mandatory diagnostic criterion in GBS; likewise marked and persistent motor asymmetry does not exclude the diagnosis of GBS.

The importance of suspecting superficial siderosis of the central nervous system in clinical practice.

Once the central nervous system surface is greatly encrusted with haemosiderin, even removing the source of bleeding will have little effect on the progression of clinical deterioration. Superficial siderosis of the central nervous system is rare and insidious, but magnetic resonance imaging has turned a previously late, mainly autoptical diagnosis into an easy, specific, in vivo, and possibly early one. Avoiding long diagnostic delay will be very important in those cases susceptible of causal treatment.

Influence of early high-dose steroid treatment on Bell's palsy evolution.

The objective of this double-blind, randomized, placebo-controlled study was to test the efficacy of high-dose prednisone, administered as early as possible, in modifying the natural progression of Bell's palsy. Sixty-two consecutive patients, enrolled within 72 hours of facial palsy onset, were assigned to high dose intravenous prednisone in combination with intramuscular polyvitaminic therapy (group A) or polyvitaminic therapy alone (group B). Clinical grading of facial muscle strength and length of absence from work were evaluated. An early worsening of facial muscle strength was observed in controls, leading to the divergence in the trends of the grading scores in the two groups; this result was not confirmed in the long-term follow-up. Treated patients returned to work earlier than controls. In conclusion, early treatment based on high-dose corticosteroids slightly accelerates spontaneous improvement in Bell's palsy.

Spontaneous intracranial hypotension: the value of brain measurements in diagnosis by MRI.

Caudal brain displacement is inconstantly reported as an MRI feature of spontaneous intracranial hypotension (SIH). We reviewed the clinical data and MRI of eight patients diagnosed as having SIH and investigated the possibility of more precise assessment. On midsagittal images we measured four anatomical landmarks: the position of the cerebellar tonsils, fourth ventricle, and infundibular recess, plus the angle between the bicommissural line and a line tangential to the floor of the fourth ventricle; midsagittal images from 89 normal controls were also measured. On statistical analysis, all measurements differed in the two groups, and the difference was significant for the cerebellar tonsils, fourth ventricle, and infundibular recess. Some overlap between patients and controls was found for each measurement; however, all the patients had two (two patients) or more (six) values outside the range in normal controls range or not above their 1st quartile. Measurement of the position of the third ventricle seemed particularly sensitive. We suggest that examination of midsagittal images can help in diagnosing clinically suspected SIH.

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.

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.

Effects of felbamate on brain polyamine changes following transient cerebral ischemia in the Mongolian gerbil.

We sought to determine whether treatment with felbamate was capable to reduce the accumulation of putrescine induced by transient forebrain ischemia in the Mongolian gerbil. Gerbils underwent 10 min ligation of common carotid arteries followed by recirculation. Immediately after the release of the arterial occlusion, felbamate (75 and 150 mg kg(-1) i.p.) was administered. Putrescine and polyamine levels were measured in hippocampus and striatum at 1, 8, 24 and 48 h after recirculation. Putrescine levels appeared enhanced already 8 h after the release of the arterial occlusion and kept increasing up to 48 h in the hippocampus and striatum. No significant changes in spermidine levels during recirculation were detected. Conversely, spermine appeared to decrease in the hippocampus while it did not show changes in the striatum. Felbamate significantly reduced the ischemia induced changes in putrescine brain content only at the dose of 150 mg kg(-1) i.p.

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.

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.

Changes in somatosensory evoked potentials following forebrain ischemia in the gerbils: effects of felbamate.

Somatosensory evoked potentials (SEPs) as well as change following transient cerebral ischemia in the gerbil were characterized in this study. SEPs were measured in each gerbil before ischemia (day -1), during ischemia, 10 min, 2, 4, 8, 24, 48 h and 8 days after recirculation. During bilateral carotid occlusion, SEP amplitude was dramatically reduced and central conduction time was significantly increased. During recirculation these values showed an improvement when compared to ischemic but not to control values. Moreover at 8 days of recirculation they were still statistically different from control values. Felbamate administration at the dose of 150 mg kg(-1), immediately after recirculation was shown to ameliorate neurophysiological recovery following cerebral ischemia.

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.

Motor evoked potentials in a case of stiff-man syndrome: a longitudinal study.

The clinical and neurophysiological findings in a patient with a typical stiff-man syndrome and their three-year evolution are described. The patient had high titers of anti-glutamic acid decarboxylase antibodies in both serum and cerebrospinal fluid. Magnetic resonance imaging (MRI) of brain and spinal cord was normal. Transcranial magnetic stimulation (TMS) revealed a distinctive motor evoked potential (MEP) pattern in proximal lower limb muscles consisting of markedly increased MEP amplitudes and MEP/M ratios, reduced excitability thresholds, and absent silent period. However, MEP latencies, central and peripheral conduction times and amplitudes obtained by magnetic spinal root stimulation were normal. Treatment with benzodiazepine and baclofen normalized both the clinical picture and the MEP values. TMS may be useful both as a diagnostic tool and to monitor the response to drug treatment.

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.

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.