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Biomedical subjects

Francesco Monaco

Publications and source records attributed to Francesco Monaco.

At least 19 recordsLinked to original sources

Antiepileptic drug-induced mania in patients with epilepsy: what do we know?

Although mood disorders have a major impact on quality of life in patients with epilepsy, the nature of some aspects, such as mania, has received little attention. With the introduction of several new antiepileptic drugs into clinical practice, attention to psychiatric treatment-emergent adverse effects has been renewed. This article explores the relationship between antiepileptic drugs and mania in patients with epilepsy, with special emphasis on the clinical pathophysiology of this phenomenon.

Anticonvulsants↗

Excitability of the human epileptic cortex after chronic valproate: a reappraisal.

We explored the action of chronic valproic acid (VPA) on the human epileptic cortex by means of transcranial magnetic stimulation (TMS). TMS is an emerging biomarker for neurotropic drugs. We had 15 drug-naive patients with different epileptic syndromes. Interictally, we measured several TMS indexes of cortical excitability before commencing VPA and 3 months later. At that time, all patients were clinical responders to the drug, whose plasma levels were in the "therapeutic range". We then compared the two conditions, while 18 healthy subjects, of whom 12 were retested at a similar delay, acted as controls. In the pooled patients, the baseline resting motor threshold to TMS was similar to that of controls, but it increased significantly (P < 0.05) after VPA. Intracortical facilitation, another index of cortical excitability, was abnormally enhanced at baseline but decreased significantly after VPA (P < 0.05). On splitting patients according to their diagnosis, the threshold increase was significant (P < 0.05) among partial, but not generalized epilepsies. The reverse was true for changes in intracortical facilitation. TMS phenomena had no linear relation to VPA serum levels. Based on the known pharmacology of TMS effects, VPA reduced the intrinsic membrane excitability of motor cortical neurons, possibly through changes in Na+ channel activity. Then, VPA corrected a transmitter-mediated interneuronal hyper-excitability of the primary motor cortex. The former effect was best seen in partial, and the latter in generalized epilepsy patients.

Adolescent↗

Fas-mediated T-cell apoptosis is impaired in patients with chronic inflammatory demyelinating polyneuropathy.

The Fas death receptor is expressed by activated lymphocytes and is involved in switching-off the immune response. Its inherited defects cause auto-immune lymphoproliferative syndrome. Impaired Fas function may also play a role in other auto-immune diseases, such as multiple sclerosis and type 1 diabetes mellitus. The aim of this work was to evaluate Fas function in T cells from patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We evaluated Fas-induced apoptosis in T-cell lines from 27 patients with CIDP, 12 patients with acute inflammatory demyelinating polyneuropathy (AIDP), and 110 controls. CIDP patients displayed lower Fas function than both AIDP patients and controls, whereas no statistically significant difference was found between AIDP patients and controls. Moreover, Fas function was lower in CIDP patients with progressive course than in those with relapsing-remitting course and lower in CIDP patients with axonal damage than in those with pure demyelination. These data suggest that defective Fas function favours CIDP development and aggressive evolution.

Adult↗

The role of aura in psychopathology and dissociative experiences in epilepsy.

Cognitive auras seem to be associated with depression and anxiety, especially in patients with temporal lobe epilepsy (TLE). Dissociative symptoms may occur as an aura or in the context of psychiatric disorders such as depression, anxiety or schizophrenia. This is a cross-sectional study of 62 patients with TLE, using personality and dissociation measures to investigate their relationship with the presence of aura and its different subtypes. Our findings show no difference in psychopathology in patients with different types of aura and reveal that dissociative symptoms correlate with specific measures of anxiety, suggesting a possible link between these experiences and anxiety disorders.

Adult↗

Combination of tizanidine and amitriptyline in the prophylaxis of chronic tension-type headache: evaluation of efficacy and impact on quality of life.

Chronic tension type headache (CTTH) has a strong impact on the Quality Of Life (QOL). We carried out an open-label randomized clinical trial on 18 patients with CTTH in order to compare two different regimens of pharmacological prophylaxis: the first provided for the use of amitriptyline 20 mg/d during 3 months, while in the second we combined amitriptyline with tizanidine (4 mg/d) in the first 3 weeks of treatment. Our hypothesis is that the combination therapy may guarantee an improvement of QOL even in the early stages of treatment. In fact, it's as well-known, there is a delay of 2-3 weeks in the prophylactic effect of amitriptyline, with a consequent persistence, in the first phases of therapy, of the headache and its negative impact. We assessed the following outcome measures: frequency, pain intensity, duration of headache and the Headache Impact Test (HIT) score, used as headache-related QOL measure. The combination therapy was effective since the first month of treatment, with a significant reduction of the headache, greater than one obtained with amitriptyline alone, in terms of frequency (-52.3% vs. -40.7%), intensity (-59.51% vs. -20.39%) and duration (-53.17% vs. -36.16%). This trend was confirmed by the HIT. Our data suggest that the combination of tizanidine with amitriptyline is faster than the amitriptyline alone in providing an improvement in the headache pattern and correlated QOL.

Adult↗

P-selectin glycoprotein ligand-1 variable number of tandem repeats (VNTR) polymorphism in patients with multiple sclerosis.

P-selectin glycoprotein ligand-1 (PSGL-1) is an important adhesion molecule involved in lymphocyte recruitment into the brain, which represents a crucial step in the pathogenesis of multiple sclerosis (MS). Three hundred twenty-one MS patients and 342 controls were genotyped for the presence of a polymorphism in the PSGL-1 gene, consisting of a variable number of tandem repeats (VNTR) originating three possible alleles: A, B and C, in order to test whether they influence the susceptibility and the course of the disease. No significant differences among allelic frequencies of A, B and C alleles in MS as compared with controls were observed. Stratifying patients according to the course of the disease, a significantly increased frequency of the shortest C allele in PP-MS was found (7.1%), either in comparison with controls (P=0.011) or with all other MS patients, who had acute inflammatory attacks at onset and an initial RR form (P=0.036). Besides, none of SP-MS patients was a carrier of the C allele and B carriers converted later from RR to SP course as compared with A/A subjects (after 15.8 rather than 8.8 years, P=0.01). In conclusion, the C allele of the VNTR polymorphism in PSGL-1 is likely to be associated with PP-MS. As this allele has been demonstrated to have a very low efficiency in mediating lymphocyte binding to brain endothelium during attacks, its high frequency in PP-MS could be related to the absence of exacerbations in such patients.

Adult↗

Obsessionality, obsessive-compulsive disorder, and temporal lobe epilepsy.

We evaluated the prevalence of obsessive-compulsive disorder (OCD) in patients with temporal lobe epilepsy (TLE) and we investigated the hypothesis that obsessionality may represent a trait in TLE. Eighty-two consecutive patients with epilepsy, 62 with TLE and 20 with idiopathic generalized epilepsy (IGE), and 82 matched healthy controls were evaluated using the SCID-IP, Y-BOCS, MMPI-2 (specifically the Psychasthenia and Obsessiveness scales), BDI, and STAI Y1 and Y2. Nine of the TLE patients, none of the IGE patients, and one of the controls had a diagnosis of OCD. Psychasthenia and Obsessiveness scores were significantly higher in the TLE than in the IGE and control groups. Patients with TLE and OCD differed significantly with respect to history of depression when compared with patients with TLE without OCD, whereas there were no differences in age at onset and duration of epilepsy, seizure pattern and frequency, MRI features, laterality of the EEG focus, antiepileptic drug therapy and combinations, and BDI scores.

Adolescent↗

Gadolinium dose optimisation in patients with multiple sclerosis: intra- and inter-individual comparisons.

OBJECTIVE: To assess the efficacy of single, double and triple doses of 1M gadolinium in the magnetic resonance (MR) evaluation of multiple sclerosis (MS) lesions in order to establish the best trade-off in terms of dose and number of injections. MATERIALS AND METHODS: Twenty-three patients with relapsing remitting or secondary progressive MS underwent MR scans of the brain, spine or both. Signal intensity, the number of enhancing lesions and the areas of MS plaque were measured in T1-weighted images before and after single, double or triple doses of contrast medium. Wilcoxon's two-sample test and the Mann-Whitney U-test were used to evaluate the differences between the groups, and between doses in the same patient. RESULTS: There was no significant difference in area signal intensity or the number of enhancing lesions between the group examined after a single injection of double-dose (DD) contrast medium and the group examined after multiple injections of a triple dose (TD). The difference in the areas of enhancement and signal intensity between a single dose (SD) and TD significantly increased after the second bolus. CONCLUSION: Gadolinium injections in MS patients can be optimised by giving a single DD bolus, which leads to the same results as a TD administered as two boli.

Adult↗

Osteopontin gene haplotypes correlate with multiple sclerosis development and progression.

Osteopontin (OPN) is an inflammatory cytokine highly expressed in multiple sclerosis (MS) plaques. In a previous work, we showed that four OPN polymorphisms form three haplotypes (A, B, and C) and that homozygotes for haplotype-A display lower OPN levels than non-AA subjects. In this work, we evaluated the distribution of these OPN haplotypes in 425 MS patients and 688 controls. Haplotype-A homozygotes had about 1.5 lower risk of developing MS than non-AA subjects. Clinical analysis of 288 patients showed that AA patients displayed slower switching from a relapsing remitting to a secondary progressive form and milder disease with slower evolution of disability. MS patients displayed increased OPN serum levels, which were partly due to the increased frequency of non-AA subjects. Moreover in AA patients, OPN levels were higher than in AA controls and similar to those found in both non-AA patients and controls, which suggests a role of the activated immune response. These data suggest that OPN genotypes may influence MS development and progression due to their influence on OPN levels.

Adult↗

E-selectin A561C and G98T polymorphisms influence susceptibility and course of multiple sclerosis.

Three hundred seven patients with MS and 300 controls were genotyped for G98T and A561C SNPs in the E-selectin gene, and genetic data were correlated with the course of the disease. The frequency of the T/T genotype of the G98T SNP was significantly increased in RR-MS patients compared with controls, while was absent in PP-MS. The frequency of the A561C SNP was significantly decreased in SP-MS compared with benign RR-MS. The T/T genotype of the G98T SNP is likely to confer an increased risk to develop MS. The A561C polymorphism seems to act as protective factor towards the progression to SP-MS.

Adenine Nucleotides↗

Consciousness, epilepsy, and emotional qualia.

The last decade has seen a renaissance of consciousness studies, witnessed by the growing number of scientific investigations on this topic. The concept of consciousness is central in epileptology, despite the methodological difficulties concerning its application to the multifaced ictal phenomenology. The authors provide an up-to-date review of the neurological literature on the relationship between epilepsy and consciousness and propose a bidimensional model (level vs contents of consciousness) for the description of seizure-induced alterations of conscious states, according to the findings of recent neuroimaging studies. The neurophysiological correlates of ictal loss and impairment of consciousness are also reviewed. Special attention is paid to the subjective experiential states associated with medial temporal lobe epilepsy. Such ictal phenomenal experiences are suggested as a paradigm for a neuroscientific approach to the apparently elusive philosophical concept of qualia. Epilepsy is confirmed to represent a privileged window over basic neurobiological mechanisms of consciousness.

Consciousness↗

Use of psychotropic drugs in patients with epilepsy: interactions and seizure risk.

It is now accepted that patients with epilepsy are more prone than the general population to develop psychiatric disorders, being significantly at risk due to psychosocial reasons, the presence of electrophysiologic and anatomopathologic abnormalities mainly in the limbic system, and because they are taking antiepileptic drugs which may have negative psychotropic effects. It is also known that many patients with epilepsy sometimes receive psychotropic medications on account of their psychiatric symptoms. This review focuses on the main problems that a clinician may encompass when treating psychiatric disorders in patients with epilepsy. On one hand, the effects of antiepileptic drugs on mood and behavior for a correct differential diagnosis of psychiatric symptoms. On the other hand, the main factors that may affect choice of therapy, patients' response and compliance, when prescribing antidepressants or antipsychotic drugs, drug interactions and the potential proconvulsive risk are reviewed.

Anticonvulsants↗

Abnormal response to glutamate of T lymphocytes from multiple sclerosis patients.

Multiple sclerosis (MS) is an immune-mediate, inflammatory and demyelinating disease of the central nervous system (CNS). Since glutamate (Glu) is a modulator of T lymphocyte function and Glu excitotoxicity has been proposed as one of the mechanisms of the demyelination, we studied the responses of T lymphocytes from normal controls (NC), MS or other non-inflammatory neurological disease (ONND) patients to Glu, by measuring phytohemagglutinin-induced intracellular Ca(2+) ([Ca(2+)](i)) rise (Fura-2 method) and cell proliferation (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide colorimetric assay). No differences in the Glu (1 microM)-induced potentiation of the [Ca(2+)](i) rise were measured in T lymphocytes from all groups of subjects, while a significant decrease in the Glu (1 mM)-induced inhibition of cell proliferation was observed in T lymphocytes from MS patients. These data demonstrate that MS T lymphocytes abnormally respond to Glu.

Adult↗

Posttraumatic epilepsy: neuroradiologic and neuropsychological assessment of long-term outcome.

PURPOSE: We sought to detect the incidence and the risk factors of posttraumatic epilepsy (PTE) in rehabilitation patients; to define the influence of PTE for late clinical and functional outcome; and to assess the cognitive and behavioral features of the patients with PTE. METHODS: Patients were examined with (a) cognitive and behavioral examinations, which included a clinical interview and psychometric tests performed by an expert clinical psychologist; (b) single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI); and (c) functional evaluation including the Glasgow Outcome Scale (GOS) and the Functional Independence Measure (FIM). RESULTS: Of the 143 patients examined in this study, in 27 (19%), seizures developed after a mean time from trauma of 11.9 +/- 8.6 months. The occurrence of PTE was significantly correlated with the hypoperfusion in temporal lobes (p < 0.004), the degree of hydrocephalus (p < 0.04), the evidence of intracerebral hematoma (p < 0.01), and operative brain injury (p < 0.001). Patients with epilepsy showed a significantly higher incidence of personality disorders than did patients without epilepsy. The uninhibited behavior, irritability, and agitated and aggressive behavior were significantly more frequent and severe in PTE patients. The psychometric tests intended to explore memory, language, intelligence, attention, and spatial cognition did not show any significant difference between those with and without epilepsy. PTE also was significantly correlated with a worse functional outcome 1 year after the trauma. CONCLUSIONS: The degrees of hydrocephalus and of hypoperfusion in the temporal lobes are significant risk factors for late PTE. Another main finding of our study is the absence of influence of epilepsy on cognitive disorders; its influence on neurobehavioral disorders and functional outcome is discussed.

Activities of Daily Living↗

Atypical antipsychotics and serotoninergic antidepressants in patients with epilepsy: pharmacodynamic considerations.

PURPOSE: To discuss the pharmacodynamic aspects of the administration of atypical antipsychotics (APs) and serotoninergic antidepressants (SSRIs) to patients with epilepsy. METHODS: This article represents an overview of all studies concerning the administration of APs and SSRIs to people with epilepsy. In particular, it deals with the relationship between neuroleptics (NLTs), APs, SSRIs, serotonin, and dopamine, with special focus on the possible epileptogenic role of psychoactive drugs. RESULTS: NLTs may induce seizures by blocking D2, H1, and.1 receptors, or by sexual hormone activation or a pharmacologic kindling mechanism. The difference among APs in their ability to induce seizures is related mainly to the percentage of D2-receptor occupancy and possibly also to their action on neurosteroids. Seizures occur at SSRIs therapeutic doses, with a 0.1-4% incidence. Coversely, in animal studies fluoxetine was claimed to exert an anticonvulsant action. CONCLUSIONS: The study of the pharmacodynamic aspects of the administration of APs and SSRIs to patients with epilepsy can help to evaluate the importance of some mechanisms of action of several psychoactive drugs in relation to their pro- or anticonvulsant activity.

Antidepressive Agents↗

Carbamazepine-risperidone interactions in patients with epilepsy.

Because concomitant administration of psychoactive and antiepileptic drugs is increasing progressively in neurologic and psychiatric practice, the aim of the current study was to evaluate the pharmacokinetic interactions between risperidone (RISP) and carbamazepine (CBZ) plasma concentrations in a group of patients with epilepsy with behavioral disturbances. The authors assessed eight patients on CBZ monotherapy (CBZ extended-release capsules) at a mean dosage of 625 +/- 253 mg/day (range, 400-1,200 mg/day) for at least 1 year. RISP (1 mg in one daily dose) was added to CBZ therapy for the occurrence of behavior disturbances. CBZ blood levels were assessed before (T0), 24 hours after (T1), and 2 weeks after (T2) RISP administration. Steady-state plasma concentrations of CBZ increased from 6.67 +/- 0.41 microg/mL at baseline to 7.37 +/- 0.59 microg/mL (p < 0.01) at T1, to 7.95 +/- 0.47 microg/mL (p < 0.0001) at T2. The pharmacokinetic data suggest either a possible role of RISP in inhibiting the cytochrome P450 microsomal enzyme system (CYP)-3A4 pathway or a potential role of CYP2D6 in CBZ metabolism.

Adult↗

Antiepileptic-antipsychotic drug interactions: a critical review of the evidence.

The potential for drug-drug interactions in psychiatry and patients with epilepsy is very high. Moreover, antiepileptic drugs are widely used outside epilepsy as psychotropic agents and their spectrum of activity on behavior is of considerable interest to psychopharmacology. In both neurologic and psychiatric practice, pharmacotherapy combinations are commonly used to treat comorbid psychiatric and neurologic disorders, to reduce or control the adverse effects of a medication or to increase its efficacy. This paper focuses on the metabolic pharmacokinetic interactions between two classes of psychotropic drugs: antiepileptic and antipsychotic drugs. The degree of documentation varies for many interactions from clinical case-report experiences to well established research outcomes. The evidence and the clinical significance of these interactions are reviewed. In general, it is better to use as few drugs as possible, as multicolored politherapies increase the possible adverse effects of drug interactions and reduce patient compliance.

Anticonvulsants↗