Predictors of Carotid Atherosclerosis Progression: Evidence from an Ultrasonography Laboratory.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the role of risk factors in predicting the variation in carotid atherosclerosis at ultrasonographic follow-up and, therefore, its role in the progression of large-vessel disease. METHODS: This retrospective population study included all the outpatients that underwent at least two carotid ultrasonographies at our laboratory from 2001 to 2017. Demographic data, vascular risk factors, and the results at follow-up were analysed to determine if correlations exist between these risk factors and variation in carotid atherosclerosis. RESULTS: Data from 600 patients (327 males and 273 females with a mean age of 67 years) were collected. The mean follow-up period was 49 months (range: 1-195). We analysed each demographic variable and risk factor to assess its correlation with a worsening of carotid atherosclerosis; previous myocardial infarction (2.594), previous carotid surgical treatment (2.368), and hypertension (1.85) were found to have the highest odds ratios, respectively. Furthermore, the sample was divided into specific subpopulations (diabetes, hypertension, and smoking), and an association was found between age and worsening stenosis. DISCUSSION AND CONCLUSIONS: Our results confirm the importance of carotid ultrasonographic follow-up in the monitoring and managing of large-vessel disease. Myocardial infarction, previous stroke, and previous surgical treatment were the strongest predictors of a worsening of carotid atherosclerosis. These findings suggest a strict follow-up is needed, even in the absence of significant carotid atherosclerosis at baseline.

A critical role of NO/cGMP/PKG dependent pathway in hippocampal post-ischemic LTP: modulation by zonisamide.

Nitric oxide (NO) is an intercellular retrograde messenger involved in several physiological processes such as synaptic plasticity, hippocampal long-term potentiation (LTP), and learning and memory. Moreover NO signaling is implicated in the pathophysiology of brain ischemia. In this study, we have characterized the role of NO/cGMP signaling cascade in the induction and maintenance of post-ischemic LTP (iLTP) in rat brain slices. Moreover, we have investigated the possible inhibitory action of zonisamide (ZNS) on this pathological form of synaptic plasticity as well as the effects of this antiepileptic drug (AED) on physiological activity-dependent LTP. Finally, we have characterized the possible interaction between ZNS and the NO/cGMP/PKG-dependent pathway involved in iLTP. Here, we provided the first evidence that an oxygen and glucose deprivation episode can induce, in CA1 hippocampal slices, iLTP by modulation of the NO/cGMP/PKG pathway. Additionally, we found that while ZNS application did not affect short-term synaptic plasticity and LTP induced by high-frequency stimulation, it significantly reduced iLTP. This reduction was mimicked by bath application of NO synthase inhibitors and a soluble guanyl cyclase inhibitor. The effect of ZNS was prevented by either the application of a NO donor or drugs increasing intracellular levels of cGMP and activating PKG. These findings are in line with the possible use of AEDs, such as ZNS, as a possible neuroprotective strategy in brain ischemia. Moreover, these findings strongly suggest that NO/cGMP/PKG intracellular cascade might represent a physiological target for neuroprotection in pathological forms of synaptic plasticity such as hippocampal iLTP.

Occipital arteriovenous malformations and migraine.

BACKGROUND: Headache has been reported to be the first clinical presentation in several patients with cerebral arteriovenous malformations (AVMs). Headache associated with AVMs often shows characteristics of migraine with and without aura. Angiographic characteristics of AVMs, such as their location, could determine the 'migraine-like' features of attacks. METHODS: We performed an observational study of the clinical and angiographic characteristics of a cohort of 40 consecutive patients with AVMs who had been admitted to our institute for endovascular embolization over a 4-year period. Headache was characterized according to ICHD-II criteria. The relationship between headaches and the angioarchitectural features of AVMs was also analysed. RESULTS: Migraine-like headache was the first clinical manifestation in 22.5% of patients. The location of the malformation was significantly associated with migraine-like presentation (p=0.03) and the occipital lobe was the predominant site. CONCLUSIONS: An occipital location may be linked with spreading depression, a pathogenic mechanism of migraine. Headache associated with arteriovenous malformations in the occipital lobe, although secondary in nature, could have clinical features similar to migraine.

Antiepileptic drugs in migraine: from clinical aspects to cellular mechanisms.

Migraine and epilepsy share several clinical features, and epilepsy is a comorbid condition of migraine. Clinical studies have shown that some antiepileptic drugs are effective at preventing migraine attacks. A rationale for their use in migraine prophylaxis is the hypothesis that migraine and epilepsy share several common pathogenetic mechanisms. An imbalance between excitatory glutamate-mediated transmission and GABA-mediated inhibition in specific brain areas has been postulated in these two pathological conditions. Moreover, abnormal activation of voltage-operated ionic channels has been implicated in both migraine and epilepsy. Cortical spreading depression has been found to be involved in the pathophysiology of epilepsy, in addition to the generation of migraine aura.

Neuronal networks and synaptic plasticity in Parkinson's disease: beyond motor deficits.

The excitatory corticostriatal pathway, which plays a critical role in the building up and storage of adaptive motor behaviours, can undergo long-lasting, activity-dependent changes in the efficacy of synaptic transmission, named long-term potentiation (LTP) and long- term depression (LTD). Both forms of plasticity are thought to underlie motor learning and depend upon the concomitant activation of glutamatergic corticostriatal and dopaminergic nigrostriatal pathways. Accordingly, corticostriatal LTP and LTD are altered in Parkinson's Disease (PD) models. The dopamine (DA)/acetylcholine(Ach) synaptic unbalance could be responsible of some of the cognitive deficits described in PD patients. The impairment of DA/ACh-dependent cellular learning could lead to the storage of unessential memory traces, as it has been postulated for the induction of L-DOPA-induced dyskinesias. Other non-motor symptoms involve not only the central dopaminergic system, but also in the noradrenergic, serotoninergic and cholinergic transmitter systems.

Pathophysiological basis of migraine prophylaxis.

Several cellular and molecular mechanisms have been implicated in migraine pathophysiology including abnormal neuronal excitability and vascular events. Drugs from different pharmacological classes are used for migraine prophylaxis. These agents may normalize neuronal excitability by modulating distinct ionic channels and various neurotransmitter systems. They can also block cortical spreading depression, prevent peripheral and/or central pain sensitization, and normalize brainstem function. Most of the drugs recently used in migraine prophylaxis have been identified by serendipidy and they have been originally approved for other indications. Subsequently, their use has been extended to migraine prevention, according to their putative mechanisms of action. More recently, trials on adequate samples of migraine patients have been conducted for several drugs. In the present review, we will present and discuss the pathophysiological bases for the use of antidepressants, beta-adrenergic blockers, calcium channel blockers and antiepileptic drugs in migraine prevention. Currently, the major classes of conventional migraine preventive drugs include the antidepressant amitriptyline, the beta-adrenergic blocker propranolol, and the antiepileptic drugs topiramate and valproic acid. Promising results have recently been obtained for angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor blockers. Some limited clinical findings have also been reported for atypical antipsychotic agents, nutritional supplements and also botulinum toxin. Targets of migraine preventive treatment are to reduce frequency and intensity of attacks and to decrease disability related to chronic headache.

Levetiracetam in newly diagnosed late-onset post-stroke seizures: a prospective observational study.

Levetiracetam (LEV) monotherapy was investigated in 35 patients (pts) (16M/19F, 71.9+/-7.3 years of age) with late-onset post-stroke seizures (i.e. seizures occurring at least 2 weeks after an ischemic stroke) in a prospective open-label study. Overall, 27 pts (77.1%) achieved a condition of seizure freedom (defined as 1 year without seizures): 19 (54.3%) at a daily LEV dose of 1000mg, 7 (20.0%) at 1500mg, 1 (2.8%) at 2000mg. Four pts (11.4%) discontinued the drug because of intolerable side effects (drowsiness associated to gait disturbance in 1 pt, and aggressive behaviour in the remaining 3 pts); 3 pts were unresponsive at a dose of 3000mg, and 1 pt was lost at follow-up. These observations suggest that LEV exhibits safety and efficacy profiles which make it an optimal candidate as a first-choice drug against post-stroke seizures.