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Biomedical subjects

Luigi Murri

Publications and source records attributed to Luigi Murri.

At least 19 recordsLinked to original sources

Absence of angiogenic genes modification in Italian ALS patients.

To investigate the role of vascular endothelial growth factor (VEGF) and angiogenin (ANG) as genetic determinants in the susceptibility to sporadic ALS in Italian patients. VEGF genotype and haplotype analysis revealed no association between any variants and the risk of ALS. Regarding ANG gene, no mutation was detected and the rs11701 polymorphism, previously described as associated with ALS, was not differently distributed between patients and controls. Overall, our data argue against the hypothesis of both genes as risk factors for motoneuron neurodegeneration, at least in an Italian population.

Amyotrophic Lateral Sclerosis↗

Intracranial hypotension syndrome following chiropractic manipulation of the cervical spine.

Cervical spine manipulation has been associated with several disorders such as cervical arteries dissection, but rarely has a relationship with intracranial hypotension been reported. We describe a patient showing intracranial hypotension syndrome following chiropractic cervical spine treatment. Magnetic resonance showed the presence of dural leakage at cervical level, suggesting the pathogenesis of the syndrome. We state that cervical spine manipulation should be considered a treatment with risk of neurological complications, including the occurrence of intracranial hypotension.

Arachnoid Cysts↗

Long-term clinical evaluation in patients with Parkinson's disease and early autonomic involvement.

OBJECTIVE: To evaluate in a prospective longitudinal study the evolution of functional disability and the response to dopaminergic therapy in PD patients with and without autonomic involvement. METHODS: Sixty untreated consecutive patients with PD underwent autonomic cardiovascular function evaluation using the five autonomic tests of Ewing. An integrated index (Autonomic Score=AS), taking in account the results of all subtests, was calculated. Patients were treated with pergolide and bromocriptine during a 5-year follow-up until the level of functional disability was sufficient to warrant the initiation of levodopa therapy. RESULTS: Results of autonomic testing were compared with those of a group of age-matched healthy subjects. A value of AS>2 was considered as indicative of autonomic failure. Eighteen patients with PD (35%) showed AS>2 (autonomically impaired group=AI), the remaining 33 (65%) had AS<2 (nonautonomically impaired group=non-AI). During the follow-up levodopa was added to the treatment regimen of 10/18 (55%) patients in AI group, and 6/33 (18%) patients in non-AI group (p<.01). CONCLUSIONS: The increased occurrence of levodopa adjunct in autonomically impaired PD suggests that there is a more rapid deterioration of functional performance in parkinsonian patients with early autonomic involvement.

Aged↗

Antimyoclonic effect of levetiracetam in MERRF syndrome.

The treatment of progressive myoclonic epilepsy (PME) is largely empirical, even though valproic acid (VPA) is usually considered the drug of first choice. However, VPA should be used with caution in PME due to mitochondrial dysfunction, i.e. in MERRF (myoclonic epilepsy with ragged red fibers) syndrome, because of its interaction with mitochondrial respiration and metabolism. Levetiracetam (LEV) treatment was started in combination with VPA in a patient with typical clinical, histological, and biochemical features of MERRF due to a mutation on the tRNA of Phenilalanine gene. The average myoclonus score improved dramatically, as well as the quality of life and no side effects were observed, even after having withdrawn VPA. LEV may benefit myoclonus in PME of mitochondrial origin without altering mitochondrial function, and it could be considered the drug of first choice for the treatment of myoclonus in MERRF.

Activities of Daily Living↗

Genes and the environment in neurodegeneration.

Neurodegenerative diseases are a heterogeneous group of pathologies which includes complex multifactorial diseases, monogenic disorders and disorders for which inherited, sporadic and transmissible forms are known. Factors associated with predisposition and vulnerability to neurodegenerative disorders may be described usefully within the context of gene-environment interplay. There are many identified genetic determinants for neurodegeneration, and it is possible to duplicate many elements of recognized human neurodegenerative disorders in animal models of the disease. However, there are similarly several identifiable environmental influences on outcomes of the genetic defects; and the course of a progressive neurodegenerative disorder can be greatly modified by environmental elements. In this review we highlight some of the major neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and prion diseases.) and discuss possible links of gene-environment interplay including, where implicated, mitochondrial genes.

Alzheimer Disease↗

MDMA and seizures: a dangerous liaison?

In the past decades, there was a massive increase in the abuse of methylenedioxymethamphetamine (MDMA) in the Western countries. Seizure onset after MDMA is considered to be related mainly to its acute systemic effects (e.g., hyponatremia and hyperthermia). However, additional mechanisms might concur to it as well. Experiments aimed at disclosing the basis for such an acute effect have the advantage of profiting of controlled conditions and the "pure" compounds, as opposed to the limits of clinical data which are biased by several confounding factors. Amphetamines exert profound effect on different monoaminergic systems, which might participate to lowering of seizure threshold. Chronic effects of MDMA abuse on seizure threshold have not been explored in detail so far. Recent data showed that in mice receiving small, repeated doses of MDMA, a persisting pro-convulsant effect toward limbic seizures and metabolic hyperexcitability can be observed. In the present article, we reviewed these studies and we report our preliminary experimental data documenting the lack of mossy fiber sprouting at short time intervals following MDMA, when seizure susceptibility is already present.

Acute Disease↗

Mitochondrial dysfunction, oxidative stress and neurodegeneration.

Mitochondria play a critical role in several metabolic processes and apoptotic pathways, regulating life cycle from the cradle to the grave. Despite the evidence of morphological, biochemical and molecular abnormalities in mitochondria in various tissues of patients with neurodegenerative disorders, the question "is mitochondrial dysfunction a necessary step in neurodegeneration?" is still unanswered. Moreover, a growing body of evidence seems to indicate that oxidative stress, which is increased in damaged mitochondria, is an earlier event associated with neurodegeneration. Here we examine the current evidences in this field, which indicate a key role of mitochondria and oxidative stress in contributing to the neurodegenerative processes.

Alzheimer Disease↗

Mitochondrial dysfunction and Alzheimer's disease: new developments.

There is substantial evidence of morphological, biochemical and molecular abnormalities in mitochondria in various tissues of patients with Alzheimer's disease (AD). However, the precise role of mitochondria in the neurodegenerative cascade leading to AD is still unclear, leaving the answer to the question "what's first: the chicken or the egg?" pending. Here we focus our attention on the progress made in this field in the past few years, which indicates a key role of this fossil organelle and of its specific DNA in contributing to the disease.

Alzheimer Disease↗

Impaired clearance of microemboli and cerebrovascular symptoms during carotid stenting procedures.

BACKGROUND: Transcranial Doppler monitoring shows a high prevalence of microemboli during carotid artery stenting (CAS); however, the occurrence of cerebrovascular symptoms (CVSs) does not seem to be related to the microembolic load. OBJECTIVE: To evaluate embolic and hemodynamic transcranial Doppler monitoring findings and their relationships with the occurrence of procedural CVSs. Patients Fifty-four patients who had carotid stenosis of more than 70% underwent a total of 57 CAS procedures during transcranial Doppler monitoring of mean blood flow velocity and microembolic signals in the middle cerebral artery. The occurrence of transient ischemic attack, transient monocular blindness, and stroke during the CAS procedure was considered CVSs. RESULTS: Nine (15.8%) of the 57 patients had CVSs during the procedure (ie, 6 patients with transient ischemic attack, 1 with transient monocular blindness, 1 with a minor stroke, and 1 with a major stroke). The mean blood flow velocity median values were statistically significantly lower (P < .001) in the group of 9 patients with CVSs (36 cm/s; interquartile range, 32.3-38.5) compared with the 48 without CVSs (48 cm/s; interquartile range, 41.5-52). The median number of isolated microembolic signals was similar in the 2 groups (72; interquartile range, 66-81 vs 75; interquartile range, 67-83.5). The median number of microembolic signal showers (clusters of too many signals to be counted separately in one cardiac cycle) presented a nonsignificant prevalence in the patients with CVSs (9; interquartile range, 7.5-11.2) compared with the ones without CVSs (8.2; interquartile range, 7-9). CONCLUSION: The low flow velocity in the middle cerebral artery may impair the clearance of the microembolic load and should be considered a precursor of CVSs during the CAS procedure.

Aged↗

Prevalence of right-to-left shunt in patients with cluster headache.

Recent investigations documented that the prevalence of right-to-left shunt (RLS) in patients with migraine with aura (MA) is significantly higher than in healthy controls and similar to prevalence of RLS in young patients with cryptogenic stroke (CS). Nevertheless, little data are available in the literature about RLS prevalence in the other forms of primary headache. The aim of this study was to investigate the occurrence of RLS in patients with cluster headache (CH). We enrolled 30 consecutive patients with CH diagnosis according to the IHS criteria and 40 controls. RLS was assessed with bilateral transcranial Doppler contrast (TCDc) monitoring of middle cerebral arteries. Eleven patients (37%) resulted positive to TCDc monitoring for evaluation of RLS. These data show that the presence of RLS in this group is more prevalent than in the general population and similar to that found in MA and in CS.

Adult↗

Sleep quality, chronotypes and preferential timing of attacks in migraine without aura.

Clinical observations show that migraine attacks have a seasonal, menstrual and circadian timing, suggesting a role of chronobiological mechanisms and their alterations in the disease, but little experimental data exists about this issue. The aim of this study was to estimate sleep quality chronotypes and the possible circadian timing of attacks in migraneurs. One hundred patients suffering from migraine without aura according to the IHS criteria (2004), and 30 controls were enrolled. Morning and evening type subjects were more represented in migraine patients than in controls and showed a tendency towards worse sleep quality and higher disability. Forty-two percent of migraineurs presented more than 75% of their attacks at night. Morning and evening types rather than intermediate and differences between real and preferred times may represent stressors that can worsen the disease. A preferential timing for occurrence of migraine attacks during the night and early morning hours was documented.

Adult↗

Daytime sleepiness in mild and moderate Alzheimer's disease and its relationship with cognitive impairment.

The increased tendency to fall asleep during the daytime together with increased wakefulness during the night has been demonstrated in patients with advanced Alzheimer's disease (AD). The aim of this study was to assess daytime sleep propensity in a cohort of patients with mild/moderate AD and to correlate it with cognitive impairment. Twenty drug-free AD patients meeting the NINCDS-ADRDA criteria for probable AD were evaluated. According to their Clinical Dementia Rating scores, subjects were classified into mild (CDR1; n=11) and moderate (CDR2; n=9) dementia patients. A group of 12 healthy subjects was taken as controls. The subjects were evaluated by the multiple sleep latency test (MSLT) after their nocturnal sleep pattern had been assessed by a polysomnographic recording throughout the night before. Both groups of AD patients showed a higher level of daytime sleepiness, which was statistically significant for mean daytime sleep latency (MDSL) (controls versus CDR1 and versus CDR2, CDR1 versus CDR2) and for 10:00 and 12:00 hour naps (controls versus CDR1, controls versus CDR2). In the entire group of AD patients, MDSL was significantly related with MMSE, De Renzi's Token test, verbal fluency, verbal digit span, story recall, Raven's Progressive Matrices, Weigl test and Benton's three-dimensional test. These data indicate that an increased sleep propensity during daytime occurs also in patients with mild/moderate AD detected by objective neurophysiological techniques.

Aged↗

Diffusion-tensor MR imaging of corticospinal tract in amyotrophic lateral sclerosis and progressive muscular atrophy.

PURPOSE: To prospectively evaluate several diffusion-tensor magnetic resonance (MR) imaging indexes (mean diffusivity [MD], fractional anisotropy [FA], and eigenvalues) of corticospinal tract impairment in patients with progressive muscular atrophy (PMA) and patients with amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: This study had institutional review board approval, and written informed consent was obtained from all subjects. Eight male patients with PMA (mean age, 63 years +/- 13 [standard deviation]), eighteen patients with ALS (14 men and four women; mean age, 64 years +/- 7), and twelve control subjects (four men and eight women; mean age, 65 years +/- 6) underwent diffusion-tensor MR imaging at which 25 spin-echo echo-planar imaging diffusion-weighted images (b = 1000 sec/mm2) were acquired along noncollinear directions. MD and FA were measured along the corticospinal tracts in each patient and subject. Changes in diffusion along and orthogonal to fiber bundles in patients were evaluated by using diffusion-tensor eigenvalues. Differences in diffusion-tensor imaging indexes between patients with PMA and those with ALS, as compared with these indexes in control subjects, were evaluated with Mann-Whitney testing. Correlations between diffusion-tensor imaging indexes and clinical variables were estimated with Pearson and Spearman rank correlation testing. RESULTS: As compared with MD (697.1 x 10(-6) mm2/sec +/- 28.1) and FA (0.585 +/- 0.032) in control subjects, MD was typically significantly increased (734.7 x 10(-6) mm2/sec +/- 41.2, P = .035) and FA significantly decreased (0.534 +/- 0.053, P = .037) along the corticospinal tracts in patients with ALS, while these parameters showed no significant change in patients with PMA (MD, 707.0 x 10(-6) mm2/sec +/- 44.2; FA, 0.559 +/- 0.028). Estimation of diffusion-tensor eigenvalues revealed normal diffusion along fiber tracts in all patients, while diffusion was increased orthogonal to fiber tracts only in patients with typical ALS. In patients with ALS, MD correlated with disease duration while FA correlated with disease severity. CONCLUSION: Diffusion-tensor MR imaging reveals corticospinal tract impairment in ALS but not in PMA.

Aged↗

Could mitochondrial haplogroups play a role in sporadic amyotrophic lateral sclerosis?

Mitochondrial impairment has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS). Furthermore, mitochondrial-specific polymorphisms were previously related to other neurodegenerative diseases, such as Parkinson, Friedreich and Alzheimer disease. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of sporadic ALS (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian patients with sALS and 151 matched controls. Individuals classified as haplogroup I demonstrated a significant decrease in risk of ALS versus individuals carrying the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4, p < 0.01). Further stratification of the dataset by sex, age and site of onset of disease and survival failed to reach significance for association. Our study provides evidence of the contribution of mitochondrial variation to the risk of ALS development in Caucasians. Further it may help elucidate the mechanism of the mitochondrial dysfunction detectable in ALS, and may be of relevance in development of strategies for the treatment of this disease.

Adult↗

Body movements during night sleep in healthy elderly subjects and their relationships with sleep stages.

In order to enlighten the profile of body movements during sleep at old age, the night sleep of twelve elderly subjects was polygraphically investigated; seven young healthy subjects were the control group. Significantly less body movements during sleep were found in the elderly compared to young subjects, meaning that the decrease in the number of body movements observed from infancy to childhood up to adulthood also continues at later ages. Differently from young adult, whose sleep body movements mainly occur in stage REM, no specific sleep state and/or stage was preferentially associated with the occurrence of body movements in the elderly. These data may point to an age-related modification in the interaction between motor cortex control and subcortical circuits. Furthermore, when body movements occur in elderly individuals, they are significantly more often followed in the next 60 s by a sleep stage change or by a spontaneous behavioural awakening. This might reflect a peculiar inability of elderly subjects to sustain stable states, and could also suggest that body movements may act as a co-factor in a process, comprising other physiological changes, leading to state shifts.

Adult↗

Dream experience during REM and NREM sleep of patients with complex partial seizures.

This study examined the effectiveness of the cognitive processes underlying dreaming in patients with complex partial seizures (CPS), by assessing the frequency of recall and the structural organization of dreams reported after awakenings provoked alternately during REM and stage 2 NREM sleep on 12 cognitively unimpaired CPS-patients (six with epileptic focus in the right hemisphere and six in the left one). Each patient was recorded for three consecutive nights, respectively, for adaptation to the sleep laboratory context, for polysomnography and for dream collection. The frequency of dream recall was lower after stage 2 NREM sleep than REM sleep, regardless of the side of epileptic focus, while the length and structural organization of dreams did not significantly differ in REM and NREM sleep. However, the length of story-like dreams was influenced by global cognitive functioning during REM sleep. These findings indicate that in CPSs-patients the elaboration of dream experience is maintained in both REM and NREM sleep, while the access to information for conversion into dream contents and the consolidation of dream contents is much less effective during NREM rather than during REM sleep. Further studies may distinguish between these two possibilities and enlighten us as to whether the impaired memory functioning during NREM sleep is a side effect of anticonvulsant treatment.

Adult↗

The role of norepinephrine in epilepsy: from the bench to the bedside.

This article provides a brief review of the role of norepinephrine (NE) in epilepsy, starting from early studies reproducing the kindling model in NE-lesioned rats, through the use of specific ligands for adrenergic receptors in experimental models of epilepsy, up to recent advances obtained by using transgenic and knock-out mice for specific genes expressed in the NE system. Data obtained from multiple experimental models converge to demonstrate the antiepileptic role of endogenous NE. This effect predominantly consists in counteracting the development of an epileptic circuit (such as in the kindling model) rather than increasing the epileptic threshold. This suggests that NE activity is critical in modifying epilepsy-induced neuronal changes especially on the limbic system. These data encompass from experimental models to clinical applications as recently evidenced by the need of an intact NE innervation for the antiepileptic mechanisms of vagal nerve stimulation (VNS) in patients suffering from refractory epilepsy. Finally, recent data demonstrate that NE loss increases neuronal damage following focally induced limbic status epilepticus, confirming a protective effect of brain NE, which has already been shown in other neurological disorders.

Adrenergic Agonists↗