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G Lauria

Publications and source records attributed to G Lauria.

At least 19 recordsLinked to original sources
PubMed2006

Progesterone and its derivatives are neuroprotective agents in experimental diabetic neuropathy: a multimodal analysis.

One important complication of diabetes is damage to the peripheral nervous system. However, in spite of the number of studies on human and experimental diabetic neuropathy, the current therapeutic arsenal is meagre. Consequently, the search for substances to protect the nervous system from the degenerative effects of diabetes has high priority in biomedical research. Neuroactive steroids might be interesting since they have been recently identified as promising neuroprotective agents in several models of neurodegeneration. We have assessed whether chronic treatment with progesterone (P), dihydroprogesterone (DHP) or tetrahydroprogesterone (THP) had neuroprotective effects against streptozotocin (STZ)-induced diabetic neuropathy at the neurophysiological, functional, biochemical and neuropathological levels. Using gas chromatography coupled to mass-spectrometry, we found that three months of diabetes markedly lowered P plasma levels in male rats, and chronic treatment with P restored them, with protective effects on peripheral nerves. In the model of STZ-induced of diabetic neuropathy, chronic treatment for 1 month with P, or with its derivatives, DHP and THP, counteracted the impairment of nerve conduction velocity (NCV) and thermal threshold, restored skin innervation density, and improved Na(+),K(+)-ATPase activity and mRNA levels of myelin proteins, such as glycoprotein zero and peripheral myelin protein 22, suggesting that these neuroactive steroids, might be useful protective agents in diabetic neuropathy. Interestingly, different receptors seem to be involved in these effects. Thus, while the expression of myelin proteins and Na(+),K(+)-ATPase activity are only stimulated by P and DHP (i.e. two neuroactive steroids interacting with P receptor, PR), NCV, thermal nociceptive threshold and intra-epidermal nerve fiber (IENF) density are also affected by THP, which interacts with GABA-A receptor. Because, a therapeutic approach with specific synthetic receptor ligands could avoid the typical side effects of steroids, future experiments will be devoted to evaluating the role of PR and GABA-A receptor in these protective effects.

20-alpha-Dihydroprogesterone↗
PubMed2005

EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy.

Skin biopsy has become a widely used tool to investigate small calibre sensory nerves including somatic unmyelinated intraepidermal nerve fibres (IENF), dermal myelinated nerve fibres, and autonomic nerve fibres in peripheral neuropathies and other conditions. Different techniques for tissue processing and nerve fibre evaluation have been used. In March 2004, a Task Force was set up under the auspices of the European Federation of Neurological Societies (EFNS) with the aim of developing guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathies. We searched the Medline database from 1989, the year of the first publication describing the innervation of human skin using immunostaining with anti-protein-gene-product 9.5 (PGP 9.5) antibodies, to 31 March 2005. All pertinent papers were rated according to the EFNS guidance. The final version of the guidelines was elaborated after consensus amongst members of the Task Force was reached. For diagnostic purposes in peripheral neuropathies, we recommend performing a 3-mm punch skin biopsy at the distal leg and quantifying the linear density of IENF in at least three 50-mum thick sections per biopsy, fixed in 2% PLP or Zamboni's solution, by bright-field immunohistochemistry or immunofluorescence with anti-PGP 9.5 antibodies (level A recommendation). Quantification of IENF density closely correlated with warm and heat-pain threshold, and appeared more sensitive than sensory nerve conduction study and sural nerve biopsy in diagnosing small-fibre sensory neuropathy. Diagnostic efficiency and predictive values of this technique were very high (level A recommendation). Confocal microscopy may be particularly useful to investigate myelinated nerve fibres, dermal receptors and dermal annex innervation. In future, the diagnostic yield of dermal myelinated nerve fibre quantification and of sweat gland innervation should be addressed. Longitudinal studies of IENF density and regeneration rate are warranted to correlate neuropathological changes with progression of neuropathy and to assess the potential usefulness of skin biopsy as an outcome measure in peripheral neuropathy trials (level B recommendation). In conclusion, punch skin biopsy is a safe and reliable technique (level A recommendation). Training in an established cutaneous nerve laboratory is recommended before using skin biopsy as a diagnostic tool in peripheral neuropathies. Quality control at all levels is mandatory.

Biopsy↗
PubMed2003

Axonal swellings predict the degeneration of epidermal nerve fibers in painful neuropathies.

OBJECTIVE: To correlate the density of swellings in intraepidermal nerve fibers (IENF) with the longitudinal measurement of the epidermal innervation density in patients with painful neuropathy and to assess the predictive value of IENF swelling to progression of neuropathy. METHODS: Fifteen patients with persistent pain in the feet underwent neurologic examination, nerve conduction studies, quantitative sensory examination, and skin biopsies at proximal thigh and distal leg. In all patients and in 15 healthy subjects, IENF density and swelling ratio (no. swellings/no. IENF) were quantified at distal leg. Follow-up study, including IENF density and swelling ratio quantification, was performed a mean of 19.2 months later. Double staining confocal microscope studies using anti-human protein-gene-product 9.5, anti-tubule, anti-neurofilament, and anti-synaptophysin antibodies were performed to assess specific accumulation within swellings. Ultrastructural investigation of IENF was also carried out. RESULTS: Patients with neuropathy had lower density of IENF and higher swelling ratio than healthy subjects (p < 0.01) at distal leg. At follow-up, patients showed a parallel decrease in both IENF density (p = 0.02) and swelling ratio (p = 0.002). However, swelling ratio remained higher (p = 0.03) than in controls. Progression of neuropathy was confirmed by the decay in sural nerve sensory nerve action potential amplitude. Double immunostaining studies suggest accumulation of tubules and ubiquitin-associated proteins within swellings. Swollen and vacuolated IENF were identified in patients with neuropathy by conventional and immuno-electron microscopy. CONCLUSIONS: Increased swelling ratio predicted the decrease in IENF density in patients with painful neuropathy. Its quantification could support earlier diagnosis of sensory axonopathy.

Adult↗
PubMed2001

Epidermal nerve fiber density in sensory ganglionopathies: clinical and neurophysiologic correlations.

We assessed the involvement of somatic unmyelinated fibers in sensory ganglionopathies by skin biopsy and quantitative sensory testing (QST). Sixteen patients with ganglionopathy, 16 with axonal neuropathy, and 15 normal controls underwent skin biopsy at the proximal thigh and the distal leg. Intraepidermal nerve fibers (IENF) were immunostained by antiprotein gene product 9.5, and their linear density was quantified under light microscopy. Confocal microscopy studies with double staining of nerve fibers and basement membrane were also performed. Healthy subjects and neuropathy patients showed the typical proximodistal gradient of IENF density; in neuropathies, values were significantly lower at the distal site of the leg, confirming the length-dependent loss of cutaneous innervation. Conversely, ganglionopathy patients with hyperalgesic symptoms did not show any change of IENF density between the proximal thigh and the distal leg. The distinct pattern of epidermal denervation seen in sensory ganglionopathy reflected the degeneration of somatic unmyelinated fibers in a fashion that was not length-dependent, which was consistent with both clinical and neurophysiologic observations and supported the diagnosis.

Biopsy↗
PubMed2000

Cranial nerve involvement in CMT disease type 1 due to early growth response 2 gene mutation.

Mutations in the gene coding for the Schwann cell transcription factor early growth response 2 (EGR2), which seems to regulate myelinogenesis and hindbrain development, have been observed in few cases of inherited neuropathy. The authors describe a unique combination of cranial nerve deficits in one member of a Charcot-Marie-Tooth 1 family carrying an EGR2 mutation (Arg381His). This finding further supports the role of EGR2 in cranial nerve development.

Adult↗
PubMed2000

Clinical and magnetic resonance imaging findings in chronic sensory ganglionopathies.

Twenty-two of 29 patients with chronic sensory ataxic neuropathy showed T2-weighted magnetic resonance imaging high signal intensity in the posterior columns of the cervical spine. T2 changes reflected the degeneration of central sensory projections and localized the disease process to T-shaped dorsal root ganglion neurons. No similar abnormalities were found in sensory and sensorimotor length-dependent axonal neuropathy patients. Spinal cord magnetic resonance imaging is a useful tool to support the clinical diagnosis of primary ganglionopathy.

Adolescent↗
PubMed1999

Epidermal innervation: changes with aging, topographic location, and in sensory neuropathy.

In previous work we demonstrated little effect of aging on the density and spatial pattern of epidermal innervation, however, this was restricted to two sites proximal and distal in the leg. To expand on these observations, we used punch skin biopsy in ten healthy controls to examine the variation in intra-epidermal nerve fiber (IENF) density at multiple specific sites in the leg. There was a consistent gradient in IENF from proximal to distal sites in all subjects, but minimal effect of age was noted. In the older age group (> or =70 years), the IENF densities ranged from 28.6+/-1.9 IENF/mm at the trunk to 15.5+/-1.5 at the distal leg. In a group of six patients with painful sensory neuropathy, we confirmed a length-dependent reduction in IENF. We observed what may be a predegenerative change, namely increased branching of epidermal nerve fibers at clinically unaffected sites. These data suggest little age-related change in IENF, at least up to age 75 years, in healthy normals. The increased branching complexity noted in unaffected sites in patients with sensory neuropathies implies that this may be a predegenerative change, preceding the actual loss of nerve fibers. Skin biopsy may be a useful tool for assessing the topographic extent and degree of nerve fiber damage in sensory neuropathies and its quantitative interpretation should be little affected by aging changes.

Adult↗
PubMed1999

Innervation of the human epidermis. A historical review.

Skin biopsy represents an attractive technique to evaluate the extensive innervation of human epidermis, as demonstrated by the immunoreactivity of the intra-epidermal nerve fibers to the marker protein gene product 9.5. Intra-epidermal nerve fibers can be reliably quantified, and their density correlates with both the presence and the severity of sensory neuropathy. The first description of nerve fibers within human epidermis was published by Paul Langerhans. However, the limitations imposed by the relatively insensitive staining methods led several investigators working during the following century to deny or minimize their existence. The author reviews the assumptions and the striking discrepancies emerging from the wide literature on cutaneous sensory terminations since the late nineteenth century and highlights the new developments emerging from the most recent works.

Animals↗
PubMed1999

Temporal trend and factors associated with delayed hospital admission of stroke patients.

The effectiveness of stroke treatment depends on the time interval between onset of symptoms and admission to hospital. The purpose of our investigation was to assess, over a 10-year period, the mean delay in admission to hospital in stroke patients to determine factors which might be associated with this delay, to define the putative number of patients available for accrual in clinical trials, and to identify strategies aimed at decreasing the time to admission. We collected data on all stroke patients consecutively admitted to our clinic from 1986 to 1995. The following variables were investigated: age, sex, educational and occupational level, home accommodation, family and personal history of vascular disease or factors known to affect the risk of vascular disease, and type and severity of stroke. The individual and independent contribution of these variables was assessed by univariate and multivariate analysis. The accurate time of stroke onset was established for 760 patients. Of these, 24.7% were admitted within 1 h from the onset of symptoms, 41% within 2 h, 54% within 4 h and 72.5% within 12 h. The mean delay was 21 +/- 2 h (SE) and the median was 3.5 h. Acute onset of neurological deficits, stroke severity and family history of cerebrovascular disease were associated with earlier presentation. According to the current guidelines for thrombolytic therapy, only 16% of the patients could have been included in a clinical trial. This study suggests that despite a relatively short time to hospital admission in most patients and an altered help-seeking behavior over time, many stroke patients did not present early enough to be recruited for clinical trials or to benefit from new treatments. The majority of patients with timely presentation were not eligible for acute treatment, or were subjects with severe stroke for whom caution is advised before initiating thrombolytic therapy. It has been suggested that the patient's indecision to seek medical help is the most important reason for a delayed hospital admission of stroke patients. These results underscore the importance of interventions aimed at reducing the delay in stroke treatment induced by patients who are unaware of the decisive role of the time of treatment induction. The finding that earliest admissions for stroke comprised patients with a previous history of cerebrovascular disease suggests that an education campaign might highlight the importance of an early admission.

Adult↗
PubMed1998

Age-related biology and diseases of muscle and nerve.

Age-related biological changes in neurons and skeletal muscle commonly affect neuromuscular function and strongly influence the expression of neuromuscular disease. Of primary importance is the attrition of entire motor units, with resultant neurogenic atrophy of skeletal muscle. Other age-related processes are sensory neuron loss, distal axonal degeneration, axonal atrophy, accumulation of multiple mitochondrial DNA mutations in muscle, and physical inactivity and deconditioning. The decline for most of these begins in early life and proceeds steadily; the curious lack of an abrupt falloff with age is not yet accounted for by any theory of pathogenesis.

Aged↗
PubMed1998

Transient global amnesia and transient ischemic attack: a community-based case-control study.

OBJECTIVES: Few case-control studies of first-ever transient global amnesia (TGA), transient ischemic attack (TIA) and normal controls have been performed to date. We aimed to assess the prevalence of cerebrovascular risk factors in a well defined population of TGA patients. MATERIAL AND METHODS: We undertook a retrospective and prospective community-based case-control study of 170 first-ever TGA, 170 first-ever TIA and 170 normal controls. RESULTS: Age-matched analysis revealed that TGA cases had a significantly lower prevalence of atrial fibrillation and diabetes mellitus than TIA controls. The prevalence of cigarette smoking and diabetes mellitus was significantly higher in normal controls than in TGA cases. CONCLUSION: Our community-based case-control study showed that atrial fibrillation and diabetes mellitus, two important risk factors for cerebrovascular disease, were significantly more common in the TIA group than in the TGA one. These results make the thromboembolic pathogenesis of TGA unlikely.

Amnesia↗
PubMed1998

An epidemiological study of multiple sclerosis in central Sardinia, Italy.

OBJECTIVES: To verify morbidity estimates in central Sardinia, Italy. METHODS: A prevalence study was performed in the province of Nuoro, Central Sardinia, which has a population of 273,768 inhabitants (135,383 men and 138,385 women). A complete enumeration approach was adopted by using all possible case-collection sources. RESULTS: On prevalence day, December 31, 1993, 394 subjects (124 men and 270 women) living in the study area were known to suffer from definite and probable MS, giving a crude prevalence rate of 143.9 cases per 100,000 people, 91.6 for males and 195.11 for females. The crude prevalence estimated on December 31, 1985, based on 282 MS cases alive in the study area, was 102.94 per 100,000. CONCLUSION: This study reinforced central Sardinia's position as a high and rising prevalence area for MS.

Adolescent↗
PubMed1998

Neuropathological alterations in diabetic truncal neuropathy: evaluation by skin biopsy.

OBJECTIVES: To describe the neuropathological features in skin biopsies from patients with diabetic truncal neuropathy. METHODS: Three patients with diabetic truncal neuropathy underwent skin biopsies from both symptomatic and asymptomatic regions of the chest and trunk. After local anaesthesia, biopsies were performed using a 3 mm diameter punch device (Acupunch). Intraepidermal nerve fibres (IENFs), the most distal processes of small myelinated and unmyelinated nerve fibres, were identified after staining with PGP 9.5 as previously described. RESULTS: Diabetes was diagnosed at the time of the neurological presentation in two, and one was a known diabetic patient. All three had associated sensory-motor polyneuropathy. In all, skin biopsies showed a marked reduction of both epidermal and dermal nerve fibres in the symptomatic dermatomes, compared with skin from asymptomatic truncal areas. In one patient, a follow up skin biopsy when symptoms had improved showed a return of IENFs. CONCLUSIONS: In diabetic truncal neuropathy, skin biopsies from symptomatic regions show a loss of IENFs. After clinical recovery, there is a return of the IENF population, suggesting that improvement occurs by nerve regeneration. These findings suggest that sensory nerve fibre injury in diabetic truncal neuropathy is distal to or within the sensory ganglia. Skin biopsy provides a possible tool for understanding the pathophysiology of the disease.

Aged↗