Successful treatment of epilepsy with serotonin reuptake inhibitors: proposed mechanism.

The widely used antidepressants Specific Serotonin Reuptake Inhibitors (SSRI) have been tried with success as anticonvulsants in cases of nonsymptomatic epilepsy. This attempt was performed on the basis of experimental data suggesting the involvement of impairments of the serotonin system in the genesis of epilepsy. This overview summarizes the clinical data and presents biochemical and neurochemical evidences suggesting the mechanism of the therapeutic effects of SSRI in nonsymptomatic epilepsy. In particular, studies on blood-borne neutral amino acids and platelet serotonin transporter (SERT) in epileptics suggest: (a) That a decreased brain availability of tryptophan may be related to some types of epilepsy. (b) That reduction of the density of SERT may be a homeostatic reaction in the brain following epileptic seizures.

The anticonvulsant effect of citalopram as an indirect evidence of serotonergic impairment in human epileptogenesis.

Some evidence would indicate that a serotonergic deficit may be involved in epileptogenesis. A preliminary trial of citalopram, a selective inhibitor of serotonin reuptake, was carried out. Citalopram 20mg/day was given to 11 non-depressed patients with poorly controlled epilepsy as an add on treatment with an open label design for 8-10 months. The median seizure frequency dropped by 55.6% in the whole group, with nine patients improving by at least 50%. No adverse reactions occurred with the exception of mild drowsiness. There were no changes of post-treatment as compared to pre-treatment AED serum concentrations. Although controlled studies are required to confirm the anticonvulsant effect of citalopram, these findings may be regarded as an indirect evidence of serotonergic impairment in human epileptogenesis.

Postvibration depression of the H-reflex as a result of a dual mechanism: an experimental study in humans.

Changes in amplitude of the soleus H (S(H))-reflex and its neurographic correlates (P(1) and P(2) waves) after vibration of the soleus muscle have been evaluated as a function of mechanical stimulation frequency, duration of the conditioning train, and test stimulus intensity. Additional experiments aimed at assessing the nervous system mechanisms underlying the postvibration depression (PVD) have been performed. In particular, homonymous (S(HMR) or S(H)) versus heteronymous (S(HTR)) soleus response, evoked respectively by tibial nerve and femoral nerve electrical stimulation, the effectiveness of sub-H threshold tibial nerve conditioning volleys on the S(HTR), and the respective effects of a brief passive stretching of the quadriceps and soleus muscles on the recovery of both the S(HMR) and S(HTR) after vibration of the homologous muscle were investigated under suitable experimental conditions. It was found that PVD occurs in the absence of changes in amplitude of the P(1) wave and the S(HTR), is paralleled by a reduced effectiveness of tibial nerve-conditioning volleys on the S(HTR) and is shortened consistently by brief passive stretching of the homologous muscle. It follows that PVD may be the result of a long-lasting reduction of the transmitter release from Ia presynaptic terminals depending, at least in part, on a protracted postvibration Ia afferent discharge caused by spindles thixotropy. These findings may provide a better understanding of the pathophysiologic mechanisms underlying spasticity in humans.

Absence of hemispheric dominance for mental rotation ability: a transcranial Doppler study.

Mean blood flow velocity (MFV) of the middle cerebral arteries was monitored in 19 healthy, adult, right-handed subjects during the resting phase and the execution of a series of neuropsychological tests: two right/left discrimination tasks, two mental rotation paradigms (the Ratcliff's test and a cube comparison test) and a phonemic fluency task, which was utilised as an internal control. In the group as a whole, the Ratcliff's test was associated with a significant bilateral increase in MFV versus both the resting state (right: p < .000001, left: p < .000001) and right/left discrimination tasks (task 1: right: p = .003, left: p = .005; task 2: right: p = .001, left: p = .001). The cube comparison in turn produced a significant increase in MFV versus both the baseline conditions (right: p < .000001, left: p < .000001) and the Ratcliff's test (right: p = .01, left: p = .002). As expected, the fluency task was associated with a significant asymmetric increase in cerebral perfusion (left > right: p = .0001). Increasing task difficulty (right/left discrimination < Ratcliffs test < cube comparison) was paralleled by a roughly proportional rise in MFV values (right: r = .424, p < .01; left: r = .331, p = .01). In conclusion, we were able to demonstrate that (1) in addition to the amount of MFV variation due to right/left discrimination (when required), mental rotation per se causes a bihemispheric activation irrespective of the experimental paradigm; (2) the MFV variation is proportional to the difficulty of the tasks.

Presynaptic and postsynaptic mechanisms underlying H-reflex changes produced by a selective voluntary contraction.

Concurrent recordings of (i) the soleus H reflex and (ii) the underlying afferent (P1) and efferent (P2) neural volleys were performed during a protracted, moderate, isometric, voluntary contraction of the soleus (S) muscle, and the subsequent release period. Besides the expected enhancement of the H reflex, muscular contraction caused a significant reduction in the corresponding central delay (as extrapolated from variations of P1-P2 interval), while the opposite trend occurred during the release phase. Control experiments, based on (a) neural blockade below the stimulation site, (b) muscle stretching at the end of the muscular contraction, (c) changes in amplitude of homonymous and heteronymous S responses, and (d) variations in effectiveness of homonymous and heteronymous conditioning volleys on the S motoneuronal pool, showed that both voluntary contraction and the subsequent release period are associated with a reduced effectiveness of la afferents, while postsynaptic motoneuronal responsiveness is significantly modified only during the actual contraction time.

Testing for pre-synaptic and post-synaptic changes in the soleus H reflex pathway following selective muscle vibration in humans.

Muscle vibration does not affect post-synaptic excitability of the corresponding motoneuronal pool, the concurrent depression of the monosynaptic reflex resulting from a pre-motoneuronal block of Ia spindle afferents. Indeed (1) both homonymous and heteronymous soleus responses (to electrical stimulation of the posterior tibial nerve (TN) and femoral nerve (FN), respectively) are clearly depressed during selective vibration of the homologous muscle (namely soleus (S) or quadriceps (Q)), but remain completely unchanged during vibration of the heterologous muscle (i.e. Q or S); (2) the effectiveness of facilitatory conditioning of FN and TN Ia afferents, respectively on the S motoneuronal pool is definitely reduced during vibration of the homologous muscle (namely Q and S).

Clinical effectiveness of lamotrigine and plasma levels in essential and symptomatic trigeminal neuralgia.

This paper reports on the effectiveness of oral lamotrigine in 15 patients suffering from "essential" trigeminal neuralgia and in five patients suffering symptomatic trigeminal neuralgia concomitant with multiple sclerosis. We recorded objective and subjective pain ratings and correlated them to daily dosage (400 mg maximum) and plasma levels of the drug. We detected pain relief proportional to daily dosage and to drug plasma levels. Eleven of the cases affected by the "essential" form of neuralgia showed complete pain relief on reaching their maximum daily dosage. All cases affected by the symptomatic form had complete pain relief. We could detect no changes from these results by the end of the follow-up period (3 to 8 months after the study ended).

Anticonvulsant effect of fluoxetine in humans.

We report an unblinded, open-label, add-on trial of fluoxetine, a selective serotonin reuptake inhibitor, in 17 patients with complex partial seizures with and without secondary generalization (mean follow-up duration, 14 +/- 1.1 months). Six patients showed complete disappearance of their daily seizures; in the others the seizure frequency was lowered by 30%. No patient reported side effects.

Scalp distribution of electrical fields related to blink reflex.

In 20 subjects the supraorbital nerve was stimulated and R1 recorded from electrodes placed over the ipsilateral orbicularis oculi muscle and from locations Fz, F8, F7, Cz, C6, C5, Pz, T4, and T3 on the scalp. The latter were referred either to an extracranial electrode or to Fz. In five subjects an artificial dipole was set at three different positions on the eyebrow and records were taken from the same derivations on the scalp to study the distribution of fields of known intensity originating from known locations. It was found that R1 could be easily detected from all scalp locations. According to its scalp distribution, three patterns were identified, which matched those of the artificial dipole. Conversely from what had been believed by previous authors, the amplitude of R1 could be larger on the contralateral scalp, according to the reference used or to the location of its origin. Therefore, it is remarked that larger amplitude contralateral to the stimulus cannot anymore be considered an exclusive feature of responses arising from the cortex. The evidence we have provided recommends a highly cautious approach in interpreting results describing trigeminal scalp responses in the latency range of R1.

Eye closure affects flash VEP latency in dementia.

In a group of 27 demented patients (21 with DAT and 6 with MID) with normal pattern VEP (PVEP), the latencies of the main flash VEP (FVEP) components (P1, N2, P2 and N3) were assessed both with open and closed eyes. At variance from controls, demented patients showed that both P2 and N3 components are significantly delayed with closed eyes while neither P1 nor N2 timings are affected. Control studies ruled out the possibility that such an outcome might depend on a defective pupillary responsiveness and/or an impaired sensitivity to luminance changes. On these grounds it is suggested that the effect of mode of stimulation on FVEP latency in demented patients is more likely to depend on "central" than on "peripheral" mechanisms. The dependence of latency changes on closure of the eyes seems to negate the direct effect of lesions upon visual structures and suggests an impairment of the modulatory action of non-visual afferents upon the activity of the visual cortex.

Orbital pseudotumor as a presenting sign of temporal arteritis.

Both unilateral proptosis (2 cases) and radiological evidence of orbital inflammatory pseudotumor in the absence of exophthalmos (1 case) have been separately described as presenting signs of temporal arteritis. We report a patient presenting with bilateral exophthalmos associated with CT and MRI signs of orbital inflammation, who had biopsy-proven temporal arteritis. Our case is unique in view of the association of the above clinical and radiological features, and the bilateral involvement of orbital tissues.

Blink reflex far fields mimicking putative cortical trigeminal evoked potentials.

The R1 component of the blink reflex was evoked by stimulation of the left supraorbital and infraorbital nerves in 10 subjects. In addition, an artificial dipole was placed over the left eyebrow, in order to simulate the occurrence of the R1 component of the blink reflex. These electrical events were recorded at scalp locations Fz, F8, F7, C6, C5, referred either to Cv7 (seventh cervical vertebra) or to Fz. It was found that the blink R1 and the field of the artificial dipole had similar behaviour across the scalp; larger amplitudes were recorded ipsilateral to the stimulus from derivations referred to Cv7, but when referred to Fz larger contralateral amplitudes were measured. In the latter condition, the scalp-recorded R1 shows similar amplitude behaviour to electrical events originating from the cortex and hence its appearance may be deceiving.

Focal cerebral ischemia and patent cardiac foramen ovale.

By means of transthoracic contrast echocardiography, the prevalence of a patent foramen ovale (PFO) was studied, in a continuous series of 48 patients aged less than 50 years with a recent episode of acute cerebral ischemia. A PFO was found in 11 subjects (23%). In the subgroup of younger patients (aged less than 30 years), the prevalence was much higher than in those aged 30 or more (58% against 11%, p = 0.0022). In the 19 patients with clear evidence of extracardiac causal factors of cerebral ischemia, there was no PFO; of the remaining 29 subjects, a PFO was present in 11 (38%) (p = 0.0015). In conclusion, the possible presence of a PFO must be carefully investigated in subjects with cerebral ischemia aged less than 30, as well as in subjects aged between 30 and 50 in whom there is no acceptable explanation for their cerebral ischemic episode.

Motor evoked potentials following cervical electrical stimulation in brachial plexus lesions.

The diagnostic relevance of recording motor evoked potentials (MEPs) after electrical stimulation of the cervical region, as compared with conventional needle electromyography (EMG), was evaluated in 26 patients with brachial plexus (BP) damage of different aetiology, severity and topography. MEP abnormalities (absence or latency increase) were observed in at least one muscle of all the patients, with a global incidence of 61.5% of the muscles examined. Neurogenic EMG signs were present in all but one patient with an incidence of 62.2% of the muscles examined. Combining the two methods, the global incidence of abnormalities rose to 69.9%. MEP abnormalities were consistent with the clinical topography and severity of BP lesions and were fairly parallel with EMG findings. Recording MEPs after percutaneous electrical stimulation of the cervical region may be regarded as a rapid, non-invasive method for quantitative electrophysiological assessment of BP damage.

Interindividual variability of central delay changes in the soleus H reflex pathway.

Central delay (CD) changes in the soleus H reflex pathway, as demonstrated by variations in the time interval between afferent (P1) and efferent (P2) neurographic volleys underlying the reflex response, were assessed in a group of normal subjects, both during the steady state and after homosynaptic spatial summation of afferent impulses. The maximal range of CD changes, regardless of whether "spontaneous" or provoked, showed significant interindividual differences whose size was positively related to the Hmax/Mmax ratio, provided that the extension of the subliminal fringe was suitably normalized. Comparatively similar variations in amplitude of the reflex motoneuronal discharge under different experimental conditions can be associated with different CD changes. Indeed, "spontaneous" CD fluctuations occurring during the steady state were consistently greater than CD reductions provoked by spatial summation, the gap size being negatively related to the Hmax/Mmax ratio.

Diagnostic relevance of trigeminal evoked potentials following infraorbital nerve stimulation.

A new tool in neurophysiological exploration of the trigeminal nerve has recently been introduced. It has been demonstrated that stimulation of the infraorbital nerve trunk gives rise to very reliable scalp responses reflecting the activity of the afferent pathway between the maximally nerve and the brain stem. The authors demonstrate that alterations of such trigeminal evoked responses fit with documented pathological processes at various locations along the trigeminal pathway (maxillary sinus, parasellar region, and within the brain-stem parenchyma). They report the findings in 68 patients suffering from "idiopathic" trigeminal neuralgia. Alterations of the response were detected in 33 cases, suggesting that some damage of the nerve had taken place either at the root entry zone into the pons (23 cases) or slightly distal to it (10 cases). Such results support the hypothesis that trigeminal neuralgia may be due to a compression of the trigeminal root at the pons entry zone.