Study of Patients Self-Training Influence on Peripheral Neuropathies Diseases Diagnosis through D.I.T.A Device.

In our daily life, the sight and the sense of touch play a fundamental role in objects recognitions. This process is helped by the experience: if a subject has already seen or already touched an object in the past, he will recognize it more easily in the future. Following this assumption, the authors of this paper wanted to investigate if the experience can influence the results of a clinical examination where the subject has an active role. The attention was focused on the peripheral neuropathies diagnosis since they require an accurate assessment of several parameters including the tactile sensitivity trend. In other words, if the tests encompass an active role of the subjects, one of the main uncertainties is the self-training that influences the subject responses. This work focuses on the study of this self-training using the D.I.T.A device (Dynamic Investigation Test-rig on hAptics). Results clearly show a fundamental role of priming during "haptic modality": expert subjects, previously experienced with the tests, demonstrated better recognition of the encountered stimuli, compared to novices. Moreover, the results show that the maximum difference between the two groups of subjects is in the first part of the test. An ANOVA analysis was carried out to demonstrate that also the errors between the pins-arrays are affected by the priming.

Technique of injection of onabotulinumtoxin A for chronic migraine: the PREEMPT injection paradigm.

In 2013 the Italian Pharmacy Agency (AIFA) approved onabotulinumtoxin A injection to prevent headaches in adult patients with chronic migraine (headaches on at least 15 days per month of which at least 8 days are with migraine) that has not responded to at least three prior pharmacological prophylaxis therapies and whose condition is appropriately managed for medication overuse. In the present paper we report the method of injection of Onabotulinumtoxin A for chronic migraine based on the PREEMPT paradigm as described by Blumenfeld et al. (Headache 50:1406-1418, 2010) adapted to our clinical setting.

Development and validation of a tactile sensitivity scale for peripheral neuropathy screening.

One of the difficult of the hands peripheral neuropathy screening uncertainty is that the current diagnosis is based not on assessments obtained by accurate and repeatable devices, but mostly on the clinical examination. So, in this paper the authors present a tactile pins-array scale determined with well-defined parameters assessed by non-invasive DITA device (Dynamic Investigation Test-rig on hAptics). This high resolution scale permits to screen the gradual tactile sensory deficit of patients affected by neuropathic diseases. The work has started with an experiment on healthy subjects penalizing their bare finger tactile sensitivity with five different pins-arrays. So, a pins-array scale divided in six levels (grouped in three ranges: low, uncertain and normal tactile sensitivity) was created. The scale was validated with a pilot study on six subjects affected by neuropathic disease. Results show an important role of the scale, supporting the clinical screening and reducing the uncertainty.

Hypertension is a factor associated with chronic daily headache.

Chronic daily headache (CDH) is one of the more frequently observed headache syndromes at major tertiary care centers. CDH is defined as headache occurring >15 days/month. Different mechanisms are involved in the development of CDH but what factors specifically contributing to the transformation from episodic into CDH remain largely unknown. Analgesic overuse is commonly identified as the most important factor for such transformation. Hypertension, allergy, asthma, arthritis, diabetes, obesity and hypothyroidism were associated with CDH in clinical series. The objective of this study is to identify risk factors of chronicity in patients with headache. A total of 1,483 consecutive patients were studied. We collected information on age, gender, headache type and comorbidity. Patients were divided into three diagnostic groups: migraine and tension-type headache (CTT) diagnosis were made according to ICHD-II, and CDH fulfilling the Proposal Headache Classification for Chronic Daily Headache described by Silberstein and Lipton (in Chronic daily headache including transformed migraine, chronic tension-type headache, and medication overuse, 2001). We used descriptive statistics and Chi-square test. Our data show that age, gender and headache onset were similar in the three groups. Diabetes, hypercolesterolaemia, smoke and cardiopathy prevalence did not differ in the three groups (P > 0.05). Hypertension prevalence in CDH group (16.2%) was significantly higher than in the other two groups (migraine 7.3%; CTT 6.6%; P < 0.01). There were no differences (P > 0.05) in hypertension prevalence between CDH with and without medication overuse. CDH patients (mean age 41.8 +/- 14) referred to the Headache Center later than migraine and CTT patients (mean age 37 +/- 12) (P > 0.05). According to previous studies we found that hypertension is more frequent in CDH than in migraine and CTT. Examining this result it is possible to conclude that there exists an association between CDH and hypertension, but not that a causal relationship necessarily exists. Considering the other somatic conditions we did not find any correlation. The potential role of somatic comorbidity in CDH has to be studied in further clinical trials.

Frontotemporal dementia: impact of P301L tau mutation on a healthy carrier.

Frontotemporal dementia (FTD) is the second commonest form of dementia after Alzheimer's disease, but its clinical and biological features are less well known. To uncover its earliest signs, we studied the main clinical, neuroimaging, and biochemical findings in an asymptomatic carrier from a three generation FTD family, bearing the P301L pathogenic mutation in the tau gene. Except for selective impairment on the Verbal Fluency Test for letters, all cognitive tests were normal. The brain computed tomography scan was normal, but the brain single photon emission computed tomography and statistical parametric mapping (SPECT-SPM) scan revealed bilateral frontal lobe hypoperfusion. Levels of total tau, 181P-tau, and Abeta1-42 in the cerebrospinal fluid were increased compared with control values. We conclude that detection of these distinctive abnormalities should improve early diagnostic accuracy for FTD and help distinguish it from Alzheimer's disease.

Olfaction in Parkinson's disease: methods of assessment and clinical relevance.

Several neurological conditions have been reported to be associated with peripheral or central deficits of olfactory system. In recent years particular emphasis has been placed on the early and severe olfactory impairment in Parkinson's disease (PD), in which limited neuropathological studies have revealed a marked dopaminergic deficit in the olfactory tubercles. Moreover, indirect evidence suggests that dysfunction of the dopaminergic pathways from mesencephalon to the piriform cortex may play a role in olfactory impairment in PD. A large number of clinical studies have reported that olfactory loss in idiopathic PD is bilateral, present in hemiparkinsonism, unrelated to the stage or clinical subtype of the disease, and independent of antiparkinsonian medication. In addition, major olfactory alterations have been reported in familial PD and dementia with Lewy bodies but not in progressive supranuclear palsy and essential tremor. These findings might stimulate further research targeted to determine the biological substrate of dissimilar olfactory performances in these movement disorders. The present review summarizes standardized procedures for the assessment of olfactory acuity (detection threshold), identification (multiple choice odor naming), discrimination (differentiation between similar/dissimilar odorants), and memory (recognition of a substance previously smelled). Specific suggestions concerning the psychometric and neuropsychological evaluation of PD patients are provided.

From the mind to the brain: an unusual pathway.

One of the most unrecognized aspects of Golgi's life was his deep interest in neuropsychiatry. From 1865 to 1868 he attended the Clinica per le Malattie Nervose e Mentali in Pavia directed by Cesare Lombroso, the founder of modern criminology. Golgi was involved in research on the etiology of psychiatric ailments. During this short period of time he produced significant theoretic advances in clinical psychiatry. However, very soon he started to criticize the conceptual approach as well as the nosological system proposed by his academic mentor. In July 1868 he left Lombroso's school in search for a more rational method of studying brain functions and diseases. In spite of his anatomical approach to the central nervous system, he always maintained curiosity in the phenomenology of functional and organic mental disorders. This predisposition is witnessed by his capability to relate clinical observations to neuropathological findings.

Assessing olfaction in the Italian population: methodology and clinical application.

Disorders of the sense of smell are receiving growing clinical as well as experimental attention. Indeed, several neurological conditions have been associated with peripheral or central deficits of the olfactory system. In recent years, particular emphasis has been attributed to the early and severe olfactory impairment in neurodegenerative diseases, such as Alzheimer's dementia and Parkinson's disease. Olfactory assessment has also been included in comprehensive pre- and post-surgical evaluations of temporal lobe epilepsy. Moreover, the request for standardized methods of olfactory evaluation by forensic and occupational medicine is greatly increasing. Despite this requirement, there is no agreement in the Italian neurological community on olfactory assessment. This lack prompted us to generate a battery of standardized tests capable of bypassing cross-cultural differences in olfactory assessment and to be potentially useful in the clinical as well as experimental settings. Procedures of assessment of olfactory acuity (detection threshold), identification (multiple choice odor naming), discrimination (differentiation between similar/dissimilar odorants) and memory (recognition of a substance previously smelled) are fully described. In order to control bias factors depending upon the nature of the investigated disorder and the applied olfactory tasks, a minimal complementary neuropsychological assessment is recommended.

High prevalence of peripheral neuropathy in hepatitis C virus infected patients with symptomatic and asymptomatic cryoglobulinaemia.

BACKGROUND: Fifty per cent of patients with chronic hepatitis C, show detectable cryoglobulinaemia, even though most of them do not show cryoglobulinaemia related symptoms. Peripheral neuropathy is present in most of the patients with symptomatic cryoglobulinaemia, where it may be the first clinical manifestation. The prevalence of peripheral neuropathy in patients with hepatitis C and cryoglobulinaemia is unknown. AIMS: To assess the prevalence of peripheral neuropathy in HCV infected patients with symptomatic or asymptomatic detectable cryoglobulinaemia. PATIENTS AND METHODS: Eighty-nine patients with HCV infection and detectable cryoglobulinaemia underwent electrophysiological studies. RESULTS: Electrophysiological evidence of peripheral neuropathy was found in 37% and was significantly associated with: the presence of cryoglobulinaemia syndrome, older age, higher rheumatoid factor reactivity and immunoglobulin M levels and reduced complement C4 activity. However, electrophysiological evidence of peripheral neuropathy was unrelated to cryocrit levels and type of cryoglobulinaemia and was found in 23/68 patients without any symptoms of cryoglobulinaemia other than pain and paresthesia. CONCLUSIONS: These findings suggest that peripheral neuropathy is frequent in patients with hepatitis C and detectable cryoglobulins. Neuropathy was found to be present in 1/3 of patients without other cryoglobulinaemia-related symptoms, thus a direct or indirect role of HCV, independent of cryoglobulinaemia, in the pathogenesis of nerve damage cannot be ruled out.

Acute quadriplegia with delayed onset and rapid recovery. Case report.

The authors describe a patient with severe head injury and sepsis who became acutely quadriplegic 3 days postinjury because of a critical illness polyneuropathy (CIP) and critical illness myopathy (CIM), which resolved rapidly after treatment of the underlying infection. In only 3 days the patient developed septic shock together with flaccid quadriplegia and absent deep tendon reflexes with no clinical or radiological evidence of central nervous system deterioration. Neurophysiological studies showed an acute axonal sensorimotor polyneuropathy, whereas the clinical course strongly suggested a concurrent myopathy. A severe Staphylococcus epidermidis infection accompanied by bacteremia was treated and the patient recovered fully within a few days. Although the case described here is unique because of its very early onset and rapid resolution, CIP and CIM are frequent complications of sepsis and multiple organ failure. The authors suggest that severely head injured patients with sepsis should be evaluated for CIP and CIM when presenting with unexplained muscle weakness or paralysis.

Lewy-body dementia and responsiveness to cholinesterase inhibitors: a paradigm for heterogeneity of Alzheimer's disease?

The concept of heterogeneity of Alzheimer's disease is based on molecular, neuropathological, clinical and neuropsychological features, and also supported by the observation that Alzheimer's patients differ in their response to pharmacological interventions. Recent investigations evaluating the therapeutic potential of cholinesterase inhibitors have disclosed the existence of at least two subsets of patients with dementia, defined as 'responders' and 'nonresponders' to this therapy. In this article, Paolo Liberini and colleagues suggest that the cluster of responders to the cholinesterase inhibitors might include a significant number of subjects with a rather selective dysfunction of the cholinergic system, as in the case of Lewy-body dementia. A neuropathological demonstration of this correlation should open up new therapeutic perspectives.

Increase of aldosterone secretion following acute haloperidol administration: possible clinical implications.

The present study was designed to investigate the effect of haloperidol on plasma corticosteroid levels in a small sample of unmediated psychiatric patients requiring acute care. Seven young male normotensive subjects in metabolic balance received a single dose of haloperidol (2 mg i.v.). Blood samples were collected for the radioimmunoassay of plasma renin activity, cortisol and aldosterone concentration at baseline and 3, 6, 12 and 24 h after injection. In five out of seven patients a significant, transient elevation of plasma aldosterone level was observed within 12 h from administration. In contrast, plasma renin activity and cortisol concentration were unchanged. Possible clinical implications of the neuroleptic-associated aldosterone elevations are discussed.

Expression of nerve growth factor in brown adipose tissue: implications for thermogenesis and obesity.

The presence of nerve growth factor (NGF) and the ability of adrenergic stimulation to affect the rate of its synthesis in mouse, rat, and human brown adipose tissue (BAT) were investigated. Addition of conditioned medium, obtained from preconfluent and confluent brown adipocytes, to PC12 cells induced typical morphological changes similar to those due to NGF itself. Anti-NGF antibodies blocked this action. Moreover, NGF mRNA was detected by RT-PCR both in BAT and in brown adipocyte preparations. That NGF is synthesized in and released from brown fat cells was confirmed by immunoblotting. When the animals were exposed to low temperatures, NGF production declined. The effect of cold exposure could be mimicked by the addition of norepinephrine (NE) at day 4 or 8 (preconfluent and confluent cells, respectively). NE depletion obtained by reserpine injection induced a drastic increase of BAT NGF production. In both rat and human BAT, immunohistochemistry identified distinct anatomical structures that express the low affinity neurotropin receptor, termed p75NGFR. BAT production of NGF was higher in genetically obese rats and mice than in their lean counterparts, a difference that becomes more evident with age. Prolonged exposure to low temperature significantly decreased the BAT NGF synthesis also in obese animals. We conclude that NGF is synthesized in and released from brown fat cells, its production being inversely dependent on sympathetic activity, in both physiological and pathophysiological conditions, and increased in genetic animal models of obesity.

Differential expression of fetal and mature tau isoforms in primary cultures of rat cerebellar granule cells during differentiation in vitro.

The molecular mechanism(s) responsible for the differential expression of various tau protein isoforms as well as their functional role in morphogenesis, neurofibrillary tangle formation and neurodegeneration have not been completely clarified. We found that the expression of tau proteins in primary cultures of cerebellar granule cells from neonatal rat brain is a developmentally regulated process affecting tau synthesis at different levels. Changes in tau RNA splicing are clearly demonstrated by PCR data showing the switching on of the mRNA containing four internal repeats by DIV 6 and the switching off of the mRNA containing three internal repeats after DIV 12. The changes in mRNA levels of the different tau isoforms during development in vitro occur in parallel with changes in tau protein expression, both qualitatively and quantitatively, as shown by Western analysis of protein extracts from granule cells at different DIV with an anti-tau polyclonal antibody. Finally, as indicated by MAP2 and tau immunocytochemistry data, the switch in tau protein expression appears to be contemporary with neurite outgrowth and cell differentiation. Our data suggest that a differential expression of various tau proteins parallels the degree of cell maturation.

NGF-mediated synaptic sprouting in the cerebral cortex of lesioned primate brain.

In the present study, coronal brain sections of cortically devascularized non-human primates (Cercopithecus aethiops) were used to assess the lesion-associated synaptic loss, and the effect of exogenous nerve growth factor (NGF) in preventing or reversing this neurodegeneration. The sections were immunolabeled with antibodies against the synaptic marker protein synaptophysin (SYN), as well as choline acetyltransferase (ChAT) and parvalbumin (PV) markers that identify cholinergic neurons and interneurons, respectively. We found that, compared to sham-operated animals, in the lesioned vehicle treated animals SYN immunoreactivity near the lesioned site in the frontoparietal cortex was decreased by 31%. Similarly, corrected optical density values of immunostained sections specific for ChAT in the nucleus basalis of Meynert (ipsilateral to the lesion) decreased by 20% and PV-immunoreactive neurons near the lesion decreased by 47%. In contrast, NGF-treated lesioned animals showed levels of SYN, ChAT, and PV immunoreactivity similar to sham controls. These results are consistent with previous studies and support the view that NGF may not only prevent neurodegenerative changes after neocortical infarction by protecting vulnerable neurons, but also is capable of inducing sprouting and synaptogenesis.

Alz-50 recognizes epitopes in primary sensory fibres and in neurons of the substantia gelatinosa of the spinal cord. An ultrastructural study in the rat.

The monoclonal antibody Alz-50 has been proposed as a marker for cellular pathological changes in Alzheimer's disease. However, it has been reported that this antibody also reacts with specific epitopes in normal individuals. Furthermore, intense Alz-50 immunoreactivity has been recently described in the hypothalamus and spinal cord of rat and monkey. In the present study, we analysed the distribution pattern of Alz-50 immunostaining in the spinal cord of the adult rat. Using light microscopy, immunostained fibres and varicosities were detected mainly in laminae I-II, although some immunostaining lamina I and the outer two thirds of lamina II. The varicosities appeared either scalloped or dome-shaped and contained numerous agranular synaptic vesicles and a few dense-core vesicles. Most varicosities were presynaptic to dendrites. A few immunostained cell bodies and dendrites were also observed, but glial cells were never immunostained. Some ultrathin sections were processed for postembedding immunogold detection of calcitonin gene-related peptide and GABA immunoreactivities. Most of the varicosities which were immunoreactive for Alz-50 also showed calcitonin gene-related peptide immunoreactivity. In contrast, GABA immunoreactivity was never co-localized with Alz-50 immunoreactivity. These results indicate that, in the superficial dorsal horn, the epitope recognized by the Alz-50 antibody is located mainly, but not exclusively, in primary sensory fibres.

Tau protein immunolocalization in fetal and adult human spinal cord.

In the present study, the monoclonal antibody Alz-50 has been used to determine and compare the immunohistochemical localization of phosphorylated tau proteins in the developing and normal adult spinal cord. At all stages of fetal life Alz-50 fiber immunoreactivity was observed in the dorsal roots, in the dorsal and dorsolateral funiculi, and in restricted regions of the dorsal horn. Alz-50 immunoreactivity was also demonstrated in the dorsal root ganglion neurons. In the adult spinal cord a consistent pattern of Alz-50 fiber immunoreactivity was localized in the superficial layers of the dorsal horn (lamina I and II) but not in dorsal and dorsolateral funiculi and in the dorsal root ganglion. Comparable results in fetal specimens have been obtained employing PHF-1, a monoclonal antibody generated against paired helical filament proteins from Alzheimer brains, while no significant immunostaining for PHF-1 was observed in the adult spinal cord. In addition, the staining with monoclonal and polyclonal anti-tau antibodies overlapped with that of Alz-50. The transient, selective pattern of Alz-50 and PHF-1 immunoreactivity may disclose some relevant functions of tau proteins during somatosensory pathway development.