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Biomedical subjects

V Gallai

Publications and source records attributed to V Gallai.

At least 37 records · Page 2Linked to original sources
PubMed2001

Levels of nerve growth factor in cerebrospinal fluid of chronic daily headache patients.

Nerve growth factor (NGF) levels were determined in the CSF of patients with chronic daily headache (CDH) and correlated with levels of sensory neuropeptides. Patients with CDH showed higher NGF levels in the CSF compared with control subjects (p < 0.0001). Higher CSF levels of substance P (SP) (p < 0.002) and calcitonin-gene-related peptide (CGRP) (p < 0.0001) were also found. There was a significant positive correlation between NGF and both SP and CGRP values. These findings suggest that NGF is involved in the long-lasting sensitization and sustained activation of the trigeminal system in CDH.

Adult↗
PubMed2001

Expression of TNF-alpha mRNA by peripheral blood mononuclear cells of multiple sclerosis patients treated with IFN-beta 1A.

The aim of the present study was to verify the expression of tumour necrosis factor (TNF)-alpha mRNA by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in unstimulated peripheral blood mononuclear cells (MNCs) of 15 relapsing-remitting multiple sclerosis (MS) patients who underwent treatment with IFN-beta 1a (6 millions of international units (MIU) i.m. once a week) and in 15 untreated MS patients matched for age and expanded disability status score (EDSS). At the same time the expression of TNF-alpha mRNA was assessed in 10 healthy age-matched control subjects. All MS patients were assessed at the basal time and after 6 months. At the basal time, the band of TNF-alpha mRNA was detectable in 12 out of the 15 untreated patients and in 13 out of the 15 patients who underwent IFN-beta 1a treatment. The higher TNF-alpha mRNA was evident in patients with gadolinium-enhancing lesions. At the 6-month follow-up, 13 out of the 15 untreated patients still had detectable values of TNF-alpha mRNA and no significant difference emerged when compared with basal time. On the contrary, the expression of TNF-alpha mRNA was absent at the same time in nine out of the 15 patients treated with IFN-beta 1a. A longitudinal analysis carried out monthly in eight MS patients (four untreated and four treated) revealed a transient increase in TNF-alpha mRNA expression in MNCs of all four treated patients in the first 3 months, supporting previous findings of an early immunoenhancing effect of IFN-beta 1a. This early activation is followed by an inhibitory effect of IFN-beta 1a on TNF-alpha mRNA expression in about 2/3 of treated MS patients when assessed at 6 months. Further long-term studies are needed to confirm this immunomodulatory effect of IFN-beta 1a not only on TNF-alpha but also on other cytokines of Th(1)and Th(2)types.

Adult↗
PubMed2001

Magnetic resonance imaging and 1H-magnetic resonance spectroscopy in amyotrophic lateral sclerosis.

We aimed to increase confidence in the combined use of MRI and proton MR spectroscopy (1H-MRS) in diagnosis of amyotrophic lateral sclerosis (ALS). We investigated 12 patients with ALS, seven definite and five probable, taking into account clinical measures of motor neuron function. On T2-weighted images we found high signal in the corticospinal tract in six and low signal in the primary motor cortex in seven of the 12 patients. Atrophy of the precentral gyrus was apparent in all the patients apart from one with probable ALS. Absolute quantification of cerebral metabolites using 1H-MRS demonstrated a significantly lower mean concentration of N-acetylaspartate (NAA) in the precentral gyrus of patients with probable and definite ALS (8.5 +/- 0.62) than in control subjects (10.4 +/- 0.71; P < 0.001). NAA concentration in primary motor cortex correlated with Norris scale scores (r = 0.30; P < 0.0001) but not with the ALS Functional Rating Scale score or disease duration. Significantly lower levels of NAA were detected in patients with low signal in the motor cortex than in those without (P < 0.01). Mean choline (Cho) and creatine (Cr) values did not differ between patients with ALS and controls.

Aged↗
PubMed2001

CSF phosphorylated tau is a possible marker for discriminating Alzheimer's disease from dementia with Lewy bodies. Phospho-Tau International Study Group.

Tau and beta-amyloid (1-42) (Abeta42) are two independent markers for the early diagnosis of Alzheimer's disease (AD). In the present study, biochemical markers were validated as tools for differential diagnosis between AD and dementia with Lewy bodies (DLB). Tau, Abeta42 and phospho-tau (181P) were measured in cerebrospinal fluid (CSF) from controls (n=40) and from patients with AD (n=80) or DLB (n=43) using the HT7-AT270 assay (prototype version). In comparison with AD, in DLB no differences were found for Abeta42 and lower phospho-tau. ROC analysis was used to compare the discriminatory power of total tau with that of phospho-tau. The area under the curve (AUC) amounted to 0.782 +/- 0.048 (mean +/- SE) for tau and to 0.839 +/- 0.042 for phospho-tau (p = 0.039) for differentiation of AD from DLB. The present results indicate that CSF phospho-tau may be a good marker for differentiation between AD and DLB.

Alzheimer Disease↗
PubMed2001

Plasma total homocysteine levels and the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene: a study in an Italian population with dementia.

Hyperhomocysteinemia is a known risk factor for vascular disease and commonly occurs in the elderly. Several studies have shown an association between elevated plasma homocysteine levels and cognitive impairment, indicating that it may play a role in the pathophysiology of dementia. We studied plasma homocysteine, folate, vitamin B12 levels and the MTHFR C677T genotype in an Italian population of patients with dementia. We confirmed that elevated plasma tHcy (>14 micromol/l) is common in elderly subjects with dementia. Although we found a high prevalence of the MTHFR TT genotype (21.2%) the allele frequency is not over-represented relative to the control population. We also observed a high incidence of folate deficiency (38%) in subjects with dementia. Elevated homocysteine was associated with low plasma folate (<5.7 nmol/l) and the MTHFR TT genotype. Moderate to severe hyperhomocysteinemia (>26.1 nmol/l) was associated with a significantly lower MMSE score. Hyperhomocysteinemia may be neurotoxic by several different mechanisms affecting cognitive function. Further studies are needed to fully explore the potential of B vitamin supplementation to lower plasma homocysteine and improve cognitive function.

Aged↗
PubMed2001

Treatment of cognitive dysfunction associated with Alzheimer's disease with cholinergic precursors. Ineffective treatments or inappropriate approaches?

The observations of the loss of cholinergic function in neocortex and hippocampus in Alzheimer's disease (AD) developed the hypothesis that replacement of cholinergic function may be of therapeutic benefit to AD patients. The different approaches proposed or tested included intervention with acetylcholine (ACh) precursors, stimulation of ACh release, use of muscarinic or nicotinic receptor agonists and acetylcholinesterase (AChE) or cholinesterase (ChE) inhibition. Inhibition of endogenous ACh degradation through ChE inhibitors and precursor loading were treatments more largely investigated in clinical trials. Of the numerous compounds in development for the treatment of AD, AChE and ChE inhibitors are the most clinically advanced, although clinical trials conducted to date did not always confirm a significant benefit of these drugs on all symptom domains of AD. The first attempts in the treatment of AD with cholinergic precursors did not confirm a clinical utility of this class of compounds in well controlled clinical trials. However, cholinergic precursors most largely used such as choline and phosphatidylcholine (lecithin) were probably not suitable for enhancing brain levels of ACh. Other phospholipids involved in choline biosynthetic pathways such as CDP-choline, choline alphoscerate and phosphatidylserine clearly enhanced ACh availability or release and provided a modest improvement of cognitive dysfunction in AD, these effects being more pronounced with choline alphoscerate. Although some positive results cannot be generalized due to the small numbers of patients studied, they probably would justify reconsideration of the most promising molecules in larger carefully controlled trials.

Age of Onset↗
PubMed2001

Activation of complement and contact system in Alzheimer's disease.

beta-Amyloid protein (betaA) has been implicated in the pathogenesis of Alzheimer's disease (AD) because of its neurotoxicity and ability to trigger a local inflammatory response. Although assembly of betaA in particular aggregates seems to be crucial event in AD pathogenesis, soluble, non-fibrillar betaA may also be involved. Non-fibrillar betaA1-42, and truncated peptide 1-28, induced dose-dependent activation of C4 sparing C3. The mechanism of C4 activation was not dependent on C1q, because non-fibrillar betaA can still activate C4 in plasma genetically deficient in C1q. A C1q independent mechanism of complement classical pathway activation could be via the activation of contact/kinin system. The possible involvement of contact system in AD is suggested by the finding that this system is massively activated in CSF of AD patients. The mechanism of activation of contact system could be the result of an anionic interaction of residues within the region 1-11 of betaA1-42 with factor XII, and of kallikrein generation. Concomitant incubation of a small cationic peptide (lysine4) with betaA abrogated its ability to trigger the cleavage of high molecular weight kininogen. In vivo, prevention of contact system activation beside the reduction of kallikrein generation, can also decrease the activation of complement system and the release of interleukin-6, both factors being considered to play an important role in the inflammatory reactions in AD brain.

Alzheimer Disease↗
PubMed2001

Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data.

This paper has reviewed the documentation on the clinical efficacy of choline alphoscerate, a cholinergic precursor, considered as a centrally acting parasympathomimetic drug in dementia disorders and in acute cerebrovascular disease. Thirteen published clinical trials, examining in total 4054 patients, have evaluated the use of choline alphoscerate in various forms of dementia disorders of degenerative, vascular or combined origin, such as senile dementia of the Alzheimer's type (SDAT) or vascular dementia (VaD) and in acute cerebrovascular diseases, such as transitory ischemic attack (TIA) and stroke. Analysis has assessed the design of each study, in particular with respect to experimental design, number of cases, duration of treatment and tests used to evaluate drug clinical efficacy. Most of the ten studies performed in dementia disorders were controlled trials versus a reference drug or placebo. Overall, 1570 patients were assessed in these studies, 854 of which in controlled trials. As detected by validated and appropriate tests, such as Mini Mental State Evaluation (MMSE) in SDAT and Sandoz Clinical Assessment Geriatric (SCAG) in VaD, administration of choline alphoscerate significantly improved patient clinical condition. Clinical results obtained with choline alphoscerate were superior or equivalent to those observed in control groups under active treatment and superior to the results observed in placebo groups. Analysis stresses the clear internal consistency of clinical data gathered by different experimental situations on the drug effect, especially with regard to the cognitive symptoms (memory, attention) characterising the clinical picture of adult-onset dementia disorders. The therapeutic usefulness of choline alphoscerate in relieving cognitive symptoms of chronic cerebral deterioration differentiates this drug from cholinergic precursors used in the past, such as choline and lecithin. Three uncontrolled trials were performed with choline alphoscerate in acute cerebrovascular stroke and TIA, totalling 2484 patients. The results of these trials suggest that this drug might favour functional recovery of patients with cerebral stroke and should be confirmed in future investigations aimed at establish the efficacy of the drug in achieving functional recovery of patients with acute cerebrovascular disease.

Cerebrovascular Disorders↗
PubMed2001

Cerebrospinal fluid acetylcholinesterase activity after long-term treatment with donepezil and rivastigmina.

At present acetylcholinesterase (AChE) inhibitors (AChEIs) represent the only reliable therapeutic resource for symptomatic treatment of Alzheimer Disease (AD). This study was designed to assess the effects of 6-12 month treatment with AChEIs donepezil and rivastigmine on cerebrospinal fluid (CSF) AChE and butyrylcholinesterase (BuChE) activity in AD patients. The pattern of AChE isoforms (G4, G1, G2) before and after treatment was investigated as well. In AD patients treated with donepezil a significant increase of CFS AChE activity was observed, whereas treatment with rivastigmine induced a significant decrease of AChE activity. Both drugs did not change BuChE activity and tended to restore the physiological pattern of AChE isoform. The possible significance of the influence of AChEIs on CSF AChE activity and isoforms is discussed.

Acetylcholinesterase↗
PubMed2001

Pharmacological treatment of non-cognitive disturbances in dementia disorders.

Behavioral and psychological symptoms of dementia (BPSD) occur in 50-90% of patients with Alzheimer's disease (AD). They cause premature institutionalization, increased costs of care and significant loss of quality-of-life for the patient and his/her family and caregivers. Non-pharmacological interventions are first-line in dealing with milder BPSD, while for moderate to severe BPSD, medication is clearly indicated in conjunction with non-pharmacological interventions. An imbalance of different neurotransmitters (acetylcholine, dopamine, noradrenaline, serotonin) has been proposed as the neurochemical correlate of BPSD. An involvement of some specific brain regions responsible for emotional activities (parahippocampal gyrus, dorsal raphe, locus coeruleus) and cortical hypometabolism have been suggested to contribute to BPSD. Atypical or novel antipsychotic drugs represent the reference drugs for treating BPSD. Among these, risperidone is considered as a drug of choice. Also, selective serotonin reuptake inhibitors (SSRIs) are useful in the treatment of BPSD.

Alzheimer Disease↗
PubMed2001

Event-related potentials in posttraumatic headache.

OBJECTIVES: To assess impairment of cognitive functions occurring in patients with posttraumatic headache as a consequence of a minor cranial trauma in the absence of organic damage involving the central nervous system. BACKGROUND: The term posttraumatic syndrome defines a stereotypic set of symptoms following traumatic brain injury that are subjective and varied. A deficit of cognitive function and impairment of the rapid processes of learning, attention, and short-term memory have frequently been identified. Moreover, headache is the most frequent symptom reported by the patients. Due to the nature of the symptoms, a great limitation in defining the posttraumatic syndrome is represented by the lack of methods and diagnostic tools that allow quantification of the subjective disturbances and evidence of the signs indicative of central nervous system involvement in this pathological condition. METHODS: Twenty-five subjects (16 women, 9 men; mean age, 28 +/- 9 years) were examined between 3 and 6 months after the traumatic event. The P300 event-related potential was recorded by an odd-ball paradigm with an acoustic modality. The patients underwent electroencephalography and brain stem auditory evoked potentials; magnetic resonance imaging was performed to exclude the presence of cerebral lesions. RESULTS: The mean latency of P300 was increased in both central electrodes (Cz and Pz) in patients with posttraumatic syndrome compared with controls (P<.001); assuming the value of mean +/- 2 SD was the cutoff point between normal and abnormal results, the P300 latency results were altered in 13 patients (52%). In the patient group, a significant correlation was demonstrated between Zung Depression Scale score and P3 and N2 wave latencies (r = 0.54, P <.004; r = 0.56, P<.003) and between Zung Anxiety Scale scores and P3 wave latencies (r = 0.46, P<.02). CONCLUSIONS: These data suggest the usefulness of the P300 event-related potential in evaluating cognitive disturbances in patients affected by posttraumatic syndrome. Alteration of cognitive potential in such patients, even in the absence of lesions detectable by neuroimaging, indicate the functional impairment of specific cerebral areas that can occur after a traumatic event.

Adolescent↗
PubMed2001

Mild hyperhomocyst(e)inemia: a possible risk factor for cervical artery dissection.

BACKGROUND AND PURPOSE: The pathogenesis of cervical artery dissection (CAD) remains unknown in most cases. Hyperhomocyst(e)inemia [hyperH(e)], an independent risk factor for cerebrovascular disease, induces damage in endothelial cells in animal cell culture. Consecutive patients with CAD and age-matched control subjects have been studied by serum levels of homocyst(e)ine and the genotype of 5,10-methylenetetrahydrofolate reductase (MTHFR). METHODS: Twenty-six patients with CAD, admitted to our Stroke Unit (15 men and 11 women; 16 vertebral arteries, 10 internal carotid arteries), were compared with age-matched control subjects. All patients underwent duplex ultrasound, MR angiography, and/or conventional angiography. RESULTS: Mean plasma homocyst(e)ine level was 17.88 micromol/L (range 5.95 to 40.0 micromol/L) for patients with CAD and 6.0+/-0.99 micromol/L for controls (P:<0.001). The genetic analysis for the thermolabile form of MTHFR in CAD patients showed heterozygosity in 54% and homozygosity in 27%; comparable figures for controls were 40% (P:=0.4) and 10% (P:=0.1), respectively. CONCLUSIONS: Mild hyperH(e) might represent a risk factor for cervical artery dissection. The MTHFR mutation is not significantly associated with CAD. An interaction between different genetic and environmental factors probably takes place in the cascade of pathogenetic events leading to arterial wall damage.

Adolescent↗
PubMed2001

Normal pressure hydrocephalus and basilar artery aneurysm. Case report and pathogenetic consideration.

The authors describe the case of a 60-year-old patient with basilar artery aneurysm who in time developed normal pressure hydrocephalus (NPH). Clinical examinations and laboratory tests did not reveal other data from which the pathology could be attributed to causes other than the vascular malformation already considered. The mechanical obstruction exerted by the aneurysm lodged on the floor of the third ventricle represents, according to the authors, the physiopathogenetic mechanism by which a temporal delay is developed between the endoventricular pulsation and that of the cerebral veins so as to produce a precise pulsatile gradient in a centrifugal direction to allow the formation of an active hydrocephalus proportional to the entity of cerebrospinal fluid (CSF) pulse.

Basilar Artery↗
PubMed2000

Cerebrospinal fluid pyruvate levels in Alzheimer's disease and vascular dementia.

Increased amounts of CSF pyruvate and lactate were found in patients with AD and patients with vascular dementia (VaD). In the AD group, CSF pyruvate values did not show any overlap with those obtained in controls; within the VaD group, the highest values were observed in possible VaD cases. A significant correlation between the severity of dementia and these biochemical parameters was also observed in both AD and possible VaD. The similarities of CSF pyruvate patterns observed in AD and possible VaD patients implicate a neurodegenerative component in this VaD subgroup.

Aged↗
PubMed2000

Nitric oxide metabolites, prostaglandins and trigeminal vasoactive peptides in internal jugular vein blood during spontaneous migraine attacks.

Despite evidence emerging from the experimental model of nitroglycerin-induced headache, the endogenous increase in nitric oxide (NO) production during migraine attacks is only speculative. It has been hypothesized that there is a close relationship between activation of the L-arginine/NO pathway and production of certain vasoactive and algogenic prostaglandins during spontaneous migraine attacks, but this suggestion also needs to be confirmed. In the present study the levels of nitrites, the stable metabolites of NO, were determined with high performance liquid chromatography (HPLC) in the internal jugular venous blood of five patients affected by migraine without aura examined ictally. These samples were taken within 30 min, 1, 2, and 4 h from the onset of the attack and at the end of the ictal period. At the same time, the plasma levels of calcitonin gene-related peptide (CGRP), neurokinin A (NKA), prostaglandin E2 (PGE2) and 6 keto PGF1alpha, the stable product of PGI2, were assessed with radioimmunoassay (RIA) kits in the same samples. The levels of the intracellular messengers, cGMP and cAMP, were also measured with the RIA method. Nitrite, cGMP, CGRP and NKA levels reached their highest values at the first hour, then they tended to decrease progressively and returned, after the end of attacks, to values similar or below those detected at the time of catheter insertion (ANOVA, statistical significance: P<0.001; P<<0.002; P<0.002; P<0.003, respectively). PGE2 and 6 keto PGF1alpha, as well as cAMP levels also significantly increased at the first hour but reached a peak at the 2nd hour and remained in the same range until the 4th and 6th hours. Then their values tended to decrease after the end of attacks, becoming lower than those measured immediately after catheter positioning for internal jugular venous blood drawing (ANOVA: P<0.002, P<0.004, P<0.001, respectively). Our results support early activation of the L-arginine/NO pathway which accompanies the release of vasoactive peptides from trigeminal endings and a late rise in the synthesis of prostanoids with algogenic and vasoactive properties which may intervene in maintaining the headache phase.

Adult↗