Luigi Maria Specchio

Adjunctive therapy versus alternative monotherapy in patients with partial epilepsy failing on a single drug: a multicentre, randomised, pragmatic controlled trial

OBJECTIVE To evaluate the value of alternative monotherapy versus adjunctive therapy in partial epilepsy refractory to single antiepileptic drug (AED) therapy. DESIGN AND METHODS In a multicentre, parallel-group, open-label study, patients with cryptogenic or symptomatic partial epilepsy not controlled after single or sequential AED monotherapies were randomised to monotherapy with an alternative AED or to adjunctive therapy with a second AED. The AED to be added/substituted and dose adjustments were determined by the physicians best judgement. Patients were followed up until withdrawal from the allocated treatment or for 12 months, whichever first. Outcome measures included proportion of patients continuing on the assigned treatment strategy, proportion of patients seizure-free after achieving the target maintenance dose, and adverse effects rates. Data were analysed by actuarial life tables, Kaplan-Meier survival analysis and Cox proportional hazard regression model. RESULTS Of a total of 157 patients (including 94 previously exposed to only one AED), 76 were randomised to alternative monotherapy and 81 to adjunctive therapy. The two groups were balanced in clinical characteristics. The 12-month cumulative probability of remaining on the assigned treatment was 55% in patients randomised to alternative monotherapy and 65% in those randomised to adjunctive therapy (P=0.74). The 12-month probability of remaining seizure-free was 14 and 16%, respectively (P=0.74). Adverse effects were similar in the two groups. No significant differences in outcome within or between groups were identified based on etiology of epilepsy and previous AED exposure. CONCLUSIONS Although these findings should be interpreted with caution due to the low statistical power resulting from the relatively small sample size, alternative monotherapy and adjunctive therapy were associated with similar outcomes. Further work is required to determine whether outcome could be improved through identification of specific AED combinations with synergistic activity.

Abnormal brain processing of cutaneous pain in patients with chronic migraine.

&NA; Syndromes with chronic daily headache include chronic migraine (CM). The reason for the transformation of migraine into chronic daily headache is still unknown. In this study, we aimed to evaluate heat pain thresholds and event‐related potentials following CO2‐laser thermal stimulation (LEPS) in hand and facial regions in patients with CM, to show changes in nociceptive brain responses related to dysfunction of pain elaboration at the cortical level. The results were compared with findings from normal control subjects and from subjects who suffer from migraine without aura. The effects of stimulus intensity, subjective pain perception and attention were monitored and compared with features of the LEPS. Twenty‐five CM patients, 15 subjects suffering from migraine without aura and 15 normal control subjects were enrolled in the study. LEPS amplitude variation was reduced in CM patients with respect to the perceived stimulus intensity, in comparison with migraine without aura patients and control subjects. In both headache groups, the distraction from the painful laser stimulus induced by an arithmetic task failed to suppress the LEPS amplitude, in comparison with control subjects. These results suggest an abnormal cortical processing of nociceptive input in CM patients, which could lead to the chronic state of pain. In both headache groups, an inability to reduce pain elaboration during an alternative cognitive task emerged as an abnormal behaviour probably predisposing to migraine.

EEG spectral analysis in migraine without aura attacks.

In 16 patients suffering from migraine without aura, we examined quantitative EEG and steady-state visual evoked potentials (SSVEPs) at 27 Hz stimulation during the critical phase of migraine and in attack-free periods. The main spontaneous EEG abnormalities found during the critical phase were the slowing and asymmetry of the dominant frequency in the alpha range. The amplitude of the SSVEP F1 component was significantly reduced during the attack phase compared with the intercritical phase; in the latter condition the visual reactivity to 27 Hz stimulus was increased over almost the entire scalp compared with normal subjects. The EEG abnormalities confirm a fluctuating modification of alpha activity during the migraine attack, probably related to a functional disorder. The suppression of visual reactivity during the migraine attack could be related to a phenomenon of neuronal depolarization such as spreading depression, occurring in a situation of central neuronal increased excitability predisposing to migraine attacks.

Modulation of trigeminal reflex excitability in migraine: effects of attention and habituation on the blink reflex

Abstract The modulation of trigeminal reflex excitability in migraine patients was evaluated during the asymptomatic phase by studying the effects of attention, habituation and preconditioning stimulus on the R2 and R3 components of the blink reflex (BR). Fifty patients suffering from migraine without aura, 20 affected by migraine with aura and 35 sex- and age-matched controls were selected. In subgroups of migraine with-aura and without-aura patients, and normal controls, the blink reflex was elicited during different cognitive situations: (a) spontaneous mental activity; (b) stimulus anticipation; (c) recognition of target numbers. In the remaining subjects, R2 and R3 habituation was evaluated by repetitive stimulation at 1, 5, 10, 15, 20, 25 and 30 s intervals. The R2 and R3 recovery curves were also computed. A reduced R3 threshold with a normal pain threshold was found in migraine with-aura and without-aura patients; the R3 component was not significantly correlated with the pain thresholds in patients and controls. The R2 and R3 components were less influenced by the warning of the stimulus in migraine without-aura and migraine with-aura patients, in comparison with the control group. A slight increase of both R2 and R3 recovery after preconditioning stimulus was also observed in migraine patients, probably caused by a phenomenon of trigeminal hyperexcitability persisting after the last attack. The abnormal BR modulation by alerting expresses in migraine a dysfunction of adaptation capacity to environmental conditions, probably predisposing to migraine.

Topographic and dipolar analysis of laser-evoked potentials during migraine attack.

Objective.—The aim of this study was to perform further evaluation of laser‐evoked potentials (LEPs) during migraine attacks using multichannel recording and topographic analysis. Specifically, this study aimed to confirm the pattern previously observed in acute migraine, while also defining the components of LEPs that are mainly modified during headache, as well as the correlation between features of LEPs and clinical variables. In addition, we aimed to conduct a dipolar source analysis of the main LEP waves in migraine patients to check the variability in the source location of LEPs during acute migraine.

Insomnia, quality of life and psychopathological features

Most of the studies about chronic insomnia focused only on specific features, providing in this way a partial outlook of the problem. The aim of this study was to examine a sample of chronic insomniacs from different points of view, by estimating the prevalence of stress, psychopathological symptoms, psychiatric disorders, changes in quality of life and illness behaviour. Forty-three patients (54.4%) experienced some psychosocial stressors in the last 6 months preceding the enrollment in the study. More than 55% of insomniacs reported symptoms of psychopathology. One or more than one psychiatric disorder was diagnosed in 61.5% of insomniacs. Life events could play a role in facilitating the transformation of a psychopathological symptom in a psychiatric disorder, since patients with a psychiatric diagnosis showed a higher percent of stress. The more noticeable disability in the group of insomniacs with psychiatric disorders and the absence of a corresponding worsening in illness behaviour suggests that insomniacs feelings about their health status are so negative to be not fatherly worsen by comorbidity in spite of a worsen disability. The evaluation of insomniacs should be as much detailed as possible, without neglecting tests for the evaluation of disability and illness behaviour, which are important not only for a correct diagnosis but also for monitoring the effects of therapies.

Glossopharyngeal neuralgia responding to pregabalin.

The author reports the use of pregabalin in a patient with glossopharyngeal neuralgia. The patient achieved complete pain relief and tolerated the medication. This is the first published report of the use of this medicine for glossopharyngeal neuralgia.

Successful Treatment of Hypnic Headache with Topiramate: A Case Report

Hypnic headache is a rare cause of benign headache in the elderly. This is a clinical report of a 67‐year‐old housewife, suffering from hypnic headache, in which topiramate yielded a successful prophylactic effect at 100 mg/day.

Photic driving response in primary headache: diagnostic value tested by discriminant analysis and artificial neural network classifiers

Abstract The aim of this study was to discriminate migraine patients (MWoA) from tension-type headache (TTH) patients and normals in order to confirm that the photic driv-ing response in the medium frequency range is a marker of migraine and to test the hypothesis that MWoA and TTH are separate disorders based on electrophysiological pattern. We recruited 120 MWoA patients, 64 TTH patients, and 51 healthy controls without any history of headache or of migraine inheritance, according to International Headache Society (IHS) criteria. The classification method was discriminant analysis using both linear discriminant analysis with a stepwise selection of predictors and an artificial neural network classifier (NNs). The mean amplitude of the first harmonic elicited by flash stimulation in the 15–27 Hz range was significantly increased over Fp1, C3, C4, P4, O2, and O1 electrodes in MWoA and TTH patients in comparison with normal subjects. Using both classification methods, only the control subjects were correctly distinguished. When only the patient groups were matched, no significant difference was detectable. The increased brain response to visual stimulation detected in both migraine and TTH suggests a common neuronal dysfunction in the two headache subtypes.

Features of the blink reflex in individuals at risk for Huntington's disease.

The aim of the study was to correlate the features of the blink reflex (BR) with the genetic abnormalities and the clinical findings in patients with Huntingtons disease (HD) and asymptomatic gene carriers. Twenty patients with HD and 20 relatives were studied. Mutation analysis was performed for the CAG expansion within the HD gene using HD 333–HD 447 as oligonucleotide primers. The BR was elicited transcutaneously by electrical stimulation of the right supraorbital nerve. The recovery curve of the R2 and R3 responses after a conditioning stimulus was evaluated. R2 latency and duration and R3 duration were significantly increased in HD patients and in presymptomatic carriers in comparison with controls; reduced R2 recovery was also clear in both HD and gene‐carrier relatives. In HD patients, the R2 latency increase correlated significantly with the severity of facial chorea. The R2 abnormalities are probably caused by impaired suprasegmental control by the basal ganglia over brainstem interneurons, which may precede the onset of involuntary movements, probably conditioning the severity of facial chorea during development of the disease.