Shared mechanisms of epilepsy, migraine and affective disorders.

Since the nineteenth century several clinical features have been observed in common between migraine and epilepsy (such as episodic attacks, triggering factors, presence of aura, frequent familiarity), but only in recent years researchers have really engaged in finding a common pathogenic mechanism. From studies of disease incidence, we understand how either migraine among patients with epilepsy or epilepsy among migraine patients are more frequent than in the general population. This association may result from a direct causality, by the same environmental risk factors and/or by a common genetic susceptibility. Ischemic events are the most frequent direct causes, especially among women and elderly people: migraine can lead to silent or clinically considerable strokes, and these ones could explain the increased risk of developing epilepsy in people with a history of migraine. Head injuries can lead headache, often with migraine characteristics, and seizures. But there are also many idiopathic cases. The comorbidity migraine-epilepsy might be explained in these cases by a neuronal hyperexcitability, which increases the risk of both diseases: a higher concentration of extracellular glutamate, the main excitatory neurotransmitter, leads in fact as a result a Cortical Spreading Depression (the pathophysiological mechanism at the base of aura) and convulsions; antiepileptic drugs such as topiramate are, therefore, used also in migraine prophylaxis. A genetic link between these two diseases is particularly evident in familial hemiplegic migraine: mutations of ATP1A2, SCN1A and CACNA1A genes, identified in this disease, have also been involved in different types of epilepsy and febrile seizures. The channelopathies, especially engaging sodium and potassium ions, can be the common pathogenic mechanism of migraine and epilepsy. Both migraine and epilepsy also have, compared to the general population, a higher prevalence and incidence of affective disorders such as anxiety, depression and suicidal ideation. Anxiety and depression can be part of symptoms that accompany migraine or seizures. Female patients with a long history of illness and frequent attacks are the most at risk. The impact of these diseases on the quality of life is the most obvious cause of these disorders, furthermore some antiepileptic drugs can have depressive effects on mood; the anxious-depressive disorders often result from the interaction between iatrogenic and psychosocial factor with common neurobiological pathogenesis. A chronic lowering of 5-HT (serotonin) levels has been demonstrated both in migraineurs and in depressed patients; amitriptyline and venlafaxine are the most indicated drugs in the treatment of migraine with comorbid depression currently. Likewise imbalance in dopamine levels has been also demonstrated: a D2 receptor genotype has been directly related to comorbidity migraine-depression. In women, hormonal fluctuations are also crucial, especially in the post-partum and late luteal phase, when the estrogenic reduction, associated with up-regulation of SNPs and down-regulation of serotonergic and GABAergic systems, increases the risk of migraine and depression. Furthermore, central sensitization phenomena have been highlighted in both diseases, and result in a progressive increase in the frequency of attacks up to chronicity and the consequent development of drug resistance and overuse. Further studies will be necessary to deepen the close relationship between these three diseases.

Expression of apoptosis-related proteins and of mRNA for dopaminergic receptors in peripheral blood mononuclear cells from patients with Alzheimer disease.

In search for biomarkers of neurodegeneration, increasing attention has been focussed on peripheral blood mononuclear cells (PBMC). In particular, PBMC from patients with Alzheimer disease (AD) have been suggested to carry apoptotic changes and alterations of neurotransmitter receptor expression, which may resemble those occurring in central nervous system neurons. We investigated the expression of apoptosis-related proteins Bcl-2, Bax, and caspase-3 and the levels of dopaminergic receptors (DR) D3 and D5 mRNA in PBMC from 17 AD patients and 11 age-matched healthy subjects. Apoptosis-related proteins were assayed by standard Western blotting analysis and DR mRNA by real-time polymerase chain reaction techniques. PBMC from healthy subjects and from AD patients expressed Bcl-2, Bax, and caspase-3 to about the same extent, and the Bcl-2/Bax ratio did not differ in the 2 groups. Levels of mRNA for DRD3 and DRD5 were similar in cells from healthy subjects and from AD patients. In conclusion, we found no evidence that PBMC from AD patients may express apoptosis-related proteins or DR mRNA to any different extent in comparison to cells from healthy subjects. These findings do not necessarily imply that immune cells cannot be exploited as biomarkers in AD (and in other central nervous system disorders). Future studies, however, should take into account the inherent complexity of the immune network.

Progression to vascular dementia of patients with mild cognitive impairment: relevance of mild parkinsonian signs.

Mild parkinsonian signs (MPS) may be found among patients presenting with mild cognitive impairment (MCI), but few data are available about the relation of these signs with the prospective risk for dementia. Our retrospective investigation considered a case-series of 119 MCI subjects followed over a three-year period: their baseline clinical picture has been analyzed in search of correlation between the cognito-motor profile and the final diagnosis. The population included 66 patients with amnesic MCI and 53 with an involvement of other cognitive areas (nonamnesic MCI). MPS were detected in 22 subjects (18.5%). At the first observation, MPS cases showed an higher frequency of nonamnesic MCI and more pronounced deficits at the Trail Making Test (p < 0.05). After a three-year follow-up, 48 patients had converted to dementia. The presence of MPS at the baseline evaluation was significantly related to the development of a vascular-type dementia. The study investigates the association between MPS and MCI and might indicate for these cases a greater risk for an involvement of executive functions and the subsequent development of vascular dementia.

[Occupational relevance of alcohol related neurological involvement]. / Comorbilità neurologica dell'alcolismo di rilevanza occupazionale e relazionale.

BACKGROUND AND OBJECTIVES: Accidents and various degrees of impairment in working performances and abilities are strongly correlated to alcohol consumption, either of moderate or of severe degree. Accidents, in particular, have been investigated in population studies that strongly suggest a direct effect of alcohol on attention and executive functions as well as a relevant interference of drinking with the neurological functioning and with eventual subclinical dysfunction of individuals: epilepsy threshold, cardiovascular risk and previous events, sleep disorders; post-traumatic sequelae. DISCUSSION AND CONCLUSIONS: Impairment of cognitive function (and concomitant functional/structural brain damage) is characterized, in particular, by difficulties in abstract problem solving, visuo-spatial and verbal learning, memory function, perceptual and motor skills, related to disruption of frontal, pontocerebellar and cerebellothalamocortical systems. These abilities should therefore be monitored in at-risk working populations in order to prevent work accidents and to address appropriate therapeutic and rehabilitative interventions.