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Biomedical subjects

Giuseppe Lauria

Publications and source records attributed to Giuseppe Lauria.

16 recordsLinked to original sources
PubMed2026

Revisiting somatosensory evoked potentials in motor neuron diseases: neurophysiological insights from a large cohort.

OBJECTIVE: To systematically investigate Somatosensory Evoked Potential (SEP) abnormalities in a large cohort of patients with Motor Neuron Disease (MND), and to explore their relationship with Motor Evoked Potentials (MEPs) and clinical phenotypes. METHODS: We retrospectively analyzed 267 patients with confirmed MND who underwent standardized SEPs and transcranial magnetic stimulation. Patients were divided into pure/predominant Upper Motor Neuron (UMN) and pure/predominant Lower Motor Neuron/Amyotrophic Lateral Sclerosis (LMN/ALS) groups. SEP abnormalities were assessed using internal normative data, including prolonged latencies, reduced amplitudes, and increased N20-P25 amplitudes. MEPs were classified semi-quantitatively as normal or abnormal by independent raters. RESULTS: At least one SEP abnormality was detected in 75&#xa0;% of patients, with no significant differences between the UMN and LMN/ALS groups. Increased N20-P25 amplitudes were observed in both phenotypes, suggesting widespread sensory cortical hyperexcitability across the MND spectrum. In contrast, abnormal MEPs were significantly more frequent in UMN patients (p&#xa0;<&#xa0;0.001). No significant association was found between SEP abnormalities and MEP findings. Upper- and lower-limb SEP latencies were strongly correlated (all p&#xa0;<&#xa0;0.001), whereas increased SEP amplitudes did not correlate with latency abnormalities. CONCLUSIONS: SEP abnormalities are highly prevalent in MND and appear largely independent from corticospinal dysfunction. Increased SEP amplitudes likely reflect primary cortical sensory hyperexcitability rather than impaired sensory conduction. SIGNIFICANCE: These findings support the concept of MND as a multisystem network disorder that involves sensory cortical circuits and highlight the role of SEPs in the diagnostic workup.

Humans↗
PubMed2007

Celiac disease presenting with motor neuropathy: effect of gluten free-diet.

Celiac disease is a rare cause of neuropathy that most commonly presents with symmetric distal sensory disturbances. We describe two patients with celiac disease in whom neuropathy presented unusually with progressive weakness of the limbs. In both patients a gluten-free diet induced a significant improvement of muscle strength and neurophysiological abnormalities, suggesting a direct pathogenetic role of sensitivity to gluten. Celiac disease should be considered in patients with idiopathic neuropathy even when gastrointestinal symptoms are absent.

Adult↗
PubMed2006

Protective effect of erythropoietin and its carbamylated derivative in experimental Cisplatin peripheral neurotoxicity.

PURPOSE: Antineoplastic drugs, such as cisplatin (CDDP), are severely neurotoxic, causing disabling peripheral neuropathies with clinical signs known as chemotherapy-induced peripheral neurotoxicity. Cotreatment with neuroprotective agents and CDDP has been proposed for preventing or reversing the neuropathy. Erythropoietin given systemically has a wide range of neuroprotective actions in animal models of central and peripheral nervous system damage. However, the erythropoietic action is a potential cause of side effects if erythropoietin is used for neuroprotection. We have successfully identified derivatives of erythropoietin, including carbamylated erythropoietin, which do not raise the hematocrit but retain the neuroprotective action exerted by erythropoietin. EXPERIMENTAL DESIGN: We have developed previously an experimental chemotherapy-induced peripheral neurotoxicity that closely resembles CDDP neurotoxicity in humans. The present study compared the effects of erythropoietin and carbamylated erythropoietin (50 microg/kg/d thrice weekly) on CDDP (2 mg/kg/d i.p. twice weekly for 4 weeks) neurotoxicity in vivo. RESULTS: CDDP given to Wistar rats significantly lowered their growth rate (P < 0.05), with slower sensory nerve conduction velocity (P < 0.001) and reduced intraepidermal nerve fibers density (P < 0.001 versus controls). Coadministration of CDDP and erythropoietin or carbamylated erythropoietin partially but significantly prevented the sensory nerve conduction velocity reduction. Both molecules preserved intraepidermal nerve fiber density, thus confirming their neuroprotective effect at the pathologic level. The protective effects were not associated with any difference in platinum concentration in dorsal root ganglia, sciatic nerve, or kidney specimens. CONCLUSIONS: These results widen the spectrum of possible use of erythropoietin and carbamylated erythropoietin as neuroprotectant drugs, strongly supporting their effectiveness.

Animals↗
PubMed2006

Expression of capsaicin receptor immunoreactivity in human peripheral nervous system and in painful neuropathies.

We describe the expression of the capsaicin receptor (TRPV1) in human peripheral nervous system (PNS) and its changes in sural nerve and skin nerve fibers of patients with painful neuropathy. Dorsal root ganglion (DRG), root, and spinal cord autopsy specimens from subjects without PNS diseases were immunoassayed with anti-TRPV1 antibodies. Bright-field and confocal microscope studies using anti-TRPV1, protein gene product 9.5 (PGP 9.5), and unique-beta-tubulin (TuJ1) antibodies were performed in skin biopsies from 15 healthy subjects and 10 painful neuropathies. The density of intraepidermal nerve fiber (IENF) labeled by each antibody was quantified. Sural nerve biopsies from three patients with painful, one patient with nonpainful diabetic neuropathy, and two patients with multifocal motor neuropathy used as controls were immunoassayed with anti-TRPV1 antibodies and investigated by immunoelectron microscopy. TRPV1 strongly labeled laminae I and II of dorsal horns, most small-size and some medium-size DRG neurons, and small-diameter axons of dorsal roots. In sural nerve, TRPV1 was expressed within the cytoplasm of most unmyelinated and some small myelinated axons, in the muscular lamina of epineural vessels, and in the endothelium of endoneurial vessels. The density of IENF labeled by TRPV1, PGP 9.5, and TuJ1 did not differ. TRPV1 colocalized with TuJ1 in all IENF and dermal nerve bundles. Painful neuropathies showed a diffuse loss of TRPV1-positive axons both in the sural nerve and in the skin. Our findings demonstrated that TRPV1 is normally expressed throughout the nociceptive pathway of PNS and that TRPV1-positive peripheral nerve fibers degenerate in painful neuropathies.

Adult↗
PubMed2006

Botulinum toxin treatment for oropharyngeal dysphagia associated with diabetic neuropathy.

OBJECTIVE: No specific treatment for oropharyngeal dysphagia related to diabetic neuropathy has been described to date. Chemical myotomy of the cricopharyngeus (CP) muscle by botulinum neurotoxin type A (BoNT/A) has been effective in reducing or abolishing dysphagia associated with upper esophageal sphincter (UES) hyperactivity of different etiologies. In the present study, we evaluated the efficacy of BoNT/A injections into the CP muscle in diabetic patients with severe oropharyngeal dysphagia associated with diabetic autonomic and/or somatic peripheral neuropathy. RESEARCH DESIGN AND METHODS: Twelve type 2 diabetic patients with severe dysphagia for both solid and liquid foods associated with autonomic and/or peripheral somatic neuropathy were investigated. Swallowing function was evaluated by clinical examination, videofluoroscopy, and simultaneous needle electromyography (EMG) of the CP and pharyngeal inferior constrictor (IC) muscles. Clinical evaluation using a four-level dysphagia severity score was performed every other day for the 1st week and thereafter every other week until week 24. Videofluoroscopy and EMG follow-up were carried out at week 1, 4, 12, 16, 18, and 24 after BoNT/A injection. BoNT/A was injected percutaneously into the CP muscle under EMG control. RESULTS: BoNT/A induced the complete recovery of dysphagia in 10 patients and had a significant (P = 0.0001, ANOVA) improvement in 2 patients within 4 +/- 1.1 days (range 3-7). Clinical improvement was confirmed by videofluoroscopy and EMG. CONCLUSIONS: Our findings suggest a potential benefit from BoNT/A treatment in dysphagia associated with diabetic neuropathy. Randomized controlled trials are needed to confirm this observation.

Anti-Dyskinesia Agents↗
PubMed2005

IgM deposits on skin nerves in anti-myelin-associated glycoprotein neuropathy.

Anti-myelin-associated glycoprotein (anti-MAG) neuropathy is a chronic demyelinating neuropathy with predominant involvement of large sensory fibers and deposits of IgM and complement on sural nerve myelinated fibers. We assessed the presence of IgM deposits on skin myelinated nerve fibers and the involvement of unmyelinated axons in anti-MAG neuropathy. Skin biopsies were performed in 14 patients with anti-MAG neuropathy, in 8 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and in 2 patients with IgM paraproteinemic neuropathy. Biopsies were taken at the proximal thigh in 20 patients, at the distal leg in 21 patients, at the proximal arm in 13 patients, and at the hand or fingertip in 10 patients. We found IgM deposits on dermal myelinated fibers in all anti-MAG neuropathy patients, with a greater prevalence at the distal site of the extremities. Deposits were located throughout the length of the fibers and at the paranodal loops. CIDP and IgM paraproteinemic neuropathies did not show any deposit of IgM. Anti-MAG neuropathy and CIPD patients showed a decrease in epidermal nerve fiber density reflecting an associated axonal loss. In anti-MAG neuropathy, both large- and small-diameter nerve fibers are affected, and specific deposits of IgM are found on skin myelinated nerve fibers.

Biopsy↗
PubMed2005

Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome.

Burning mouth syndrome is a common disorder that frequently affects women in the 5th-7th decade. It is characterized by persisting painful symptoms mainly involving the anterior two-thirds of the tongue. For several years it has been attributed to psychological causes. We investigated the innervation of the epithelium of the tongue to assess whether damage of peripheral nerve fibers underlies the pathogenesis of the disease. We examined 12 patients with clinically definite burning mouth syndrome for at least 6 months. We obtained superficial biopsies of the lateral aspect of the anterior two-thirds of the tongue from all patients and nine healthy controls. Immunohistochemical and confocal microscope co-localization studies were performed with cytoplasmatic, cytoskeletric, Schwann cell, and myelin markers for pathological changes. The density of epithelial nerve fibers was quantified. Patients showed a significantly lower density of epithelial nerve fibers than controls, with a trend toward correlation with the duration of symptoms. Epithelial and sub-papillary nerve fibers showed diffuse morphological changes reflecting axonal degeneration. Our study demonstrates that burning mouth syndrome is caused by a trigeminal small-fiber sensory neuropathy and that superficial biopsy of the tongue can be helpful in assessing the diagnosis. These findings shed light into the pathogenesis of this common disorder and could contribute to evaluate targeted therapies in patients.

Aged↗
PubMed2005

Sensory neuron diseases.

Sensory neuron diseases (SND) are a distinct subgroup of peripheral-nervous-system diseases, first acknowledged in 1948. Acquired SND have a subacute or chronic course and are associated with systemic immune-mediated diseases, vitamin intoxication or deficiency, neurotoxic drugs, and life-threatening diseases such as cancer. SND are commonly idiopathic but can be genetic diseases; the latter tend to involve subtypes of sensory neurons and are associated with certain clinical pictures. The loss of sensory neurons in dorsal root ganglia causes the degeneration of short and long peripheral axons and central sensory projections in the posterior columns. This pathological process leads to a pattern of sensory nerve degeneration that is not length dependent and explains distinct clinical and neurophysiological abnormalities. Here we propose a comprehensive approach to the diagnosis of acquired and hereditary SND and discuss clinical, genetic, neurophysiological, neuroradiological, and neuropathological assessments.

Ganglia, Spinal↗
PubMed2005

Small fibre neuropathies.

PURPOSE OF REVIEW: To summarize the recent advances in aetiology, diagnostic assessment, and treatment of small fibre neuropathies. RECENT FINDINGS: New causes of small fibre neuropathy have been recognized and advances in neurophysiologic and neuropathologic techniques for investigating small fibres have been made, increasing the interest in this field. In particular, skin biopsy proved to be a sensitive method to diagnose small fibre neuropathy. It allows the detection of subclinical abnormalities of peripheral nerve function in patients with diabetes and tongue denervation in patients with burning mouth syndrome. This technique has also been used to demonstrate the neuroprotective effect of erythropoietin in experimental models of neuropathy. Among nonconventional neurophysiologic techniques for investigating small fibres, laser-evoked potential and contact heat-evoked potential stimulators have been developed and deserve particular interest. Several trials on neuropathic pain that is a typical feature of small fibre neuropathies have been performed and guidelines have recently been published. SUMMARY: Detection of small fibre impairment allows earlier diagnosis of neuropathy and could be used as an outcome measure in future regenerative neuropathy trials. Standardization of skin biopsy can have an important impact on clinical practice and research. Further studies are needed to assess the reliability of current neurophysiologic techniques for testing small fibre function in peripheral neuropathies and the correlation with well established neuropathologic examination.

Animals↗
PubMed2005

Intraepidermal nerve fiber density in rat foot pad: neuropathologic-neurophysiologic correlation.

Quantification of cutaneous innervation in rat footpad is a useful tool to investigate sensory small-diameter nerve fibers, which are affected early in peripheral neuropathies. The aim of this work was to provide normative reference data on the density of intraepidermal nerve fibers (IENFs) and Langerhans cells in the hindpaw footpad of Sprague-Dawley and Wistar rats. We also evaluated the sensibility of IENF density by comparing neuropathologic findings with neurophysiologic examination and the presence of peripheral neuropathy in two well-characterized animal models of neuropathy. IENF density was quantified in 22 Sprague-Dawley rats and 13 Wistar rats and compared with 19 age-matched Sprague-Dawley rats with streptozotocin-induced diabetic neuropathy and 30 age-matched Wistar rats with cisplatin- or paclitaxel-induced neuropathy. Antidromic tail sensory nerve conduction velocity (SNCV) was assessed in all animals. IENF and Langerhans cell densities were constant in healthy Sprague-Dawley rats at any age, and they were similar to those observed in healthy Wistar rats. In neuropathic rats, both SNCV and IENF density were significantly reduced with respect to controls. Quantification of IENF density was significantly correlated with changes in conduction velocity. Diabetic neuropathy rats alone showed a significantly higher density of Langerhans cells compared with controls. Our study demonstrated that IENF density quantification correlates with SNCV changes and suggests that this might represent a useful outcome measurement in experimental neuropathies.

Animals↗
PubMed2004

Erythropoietin both protects from and reverses experimental diabetic neuropathy.

Erythropoietin (EPO) possesses generalized neuroprotective and neurotrophic actions. We tested the efficacy of recombinant human EPO (rhEPO) in preventing and reversing nerve dysfunction in streptozotocin (STZ)-induced diabetes in rats. Two days after STZ [60 mg/kg of body weight (b.w.), i.p.], diabetic animals were administered rhEPO (40 microg/kg of b.w.) three times weekly for 5 weeks either immediately (preventive) before or after a 5-week delay (therapeutic) after induction of hyperglycemia or at a lower dose (8 microg/kg of b.w. once per week) for 8 weeks (prolonged). Tail-nerve conduction velocities (NCV) was assessed at 5 and 11 weeks for the preventive and therapeutic schedule, respectively. Compared to nondiabetic rats, NCV was 20% lower after 5 weeks in the STZ group, and this decrease was attenuated 50% by rhEPO. Furthermore, the reduction of Na(+),K(+)-ATPase activity of diabetic nerves (by 55%) was limited to 24% in the rhEPO-treated group. In the therapeutic schedule, NCV was reduced by 50% after 11 weeks but by only 23% in the rhEPO-treated group. rhEPO treatment attenuated the decrease in compound muscle action potential in diabetic rats. In addition, rhEPO treatment was associated with a preservation of footpad cutaneous innervation, as assessed by protein gene product 9.5 immunostaining. Diabetic rats developed alterations in mechanical and thermal nociception, which were partially reversed by rhEPO given either in a preventative or therapeutic manner. These observations suggest that administration of rhEPO or its analogues may be useful in the treatment of diabetic neuropathy.

Animals↗
PubMed2004

Tubule and neurofilament immunoreactivity in human hairy skin: markers for intraepidermal nerve fibers.

The cytoplasmic protein gene product 9.5 (PGP 9.5) is considered a reliable marker for intraepidermal nerve fibers (IENFs). However, PGP 9.5 expression has never been compared with antibodies against the main components of the cytoskeleton. We compared the density of PGP 9.5-positive IENF at the leg with that obtained using a panel of antibodies specific for certain cytoskeletal components, namely, anti-unique beta-tubulin (TuJ1), anti-nonphosphorylated microtubule-associated protein-1B (MAP1B), anti-70 and 200 KDa neurofilament (NF), and antiphosphorylated neurofilament (SMI 312), in 15 healthy subjects and in 10 patients with painful neuropathy. We also performed colocalization studies and investigated the relationship between IENFs and Schwann cells. In both controls and neuropathies, the density of IENF labeled by PGP 9.5, TuJ1, and MAP1B did not differ, whereas that of NF and SMI 312 was significantly lower. Double-staining studies confirmed that antibodies against cytoskeletal markers can be used to reliably stain skin nerve fibers, suggesting that they might provide insight into specific axonal impairment in peripheral neuropathies.

Biomarkers↗
PubMed2003

Neurophysiological diagnosis of acquired sensory ganglionopathies.

We examined 29 patients with chronic progressive ganglionopathy of different etiology. Neurophysiological abnormalities were dominated by a widespread decrease in sensory nerve action potential amplitudes, which involved both upper and lower limb nerves, even in patients with asymmetrical or patchy clinical presentation. This impairment of sensory nerve conduction, reflecting a nonlenght-dependent pattern of peripheral axon degeneration, should be considered the hallmark of ganglionopathies. The evidence of central sensory pathway impairment, which allows to localize the pathology to the dorsal root ganglion neurons, could be better confirmed by cervical magnetic resonance imaging, which showed a diffuse hyperintensity in the posterior columns in all patients, than by somatosensory evoked potentials, which were undetectable in most of the patients. Few patients showed an impairment of individual motor nerves, which appeared more severe in paraneoplastic associated ganglionopathies. Neurophysiological abnormalities did not appear significantly changed at the 4-year follow-up. We emphasize that distinct abnormalities allow to differentiate ganglionopathies from axonal sensory neuropathies on routine neurophysiological examination.

Action Potentials↗