Clinical experience with intravenous valproate as first-line treatment of status epilepticus and seizure clusters in selected populations.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of intravenous valproate (i.v. VPA) as first-line treatment of status epilepticus (SE) and seizure clusters in selected patient populations. METHODS: We enrolled 23 patients (11 females and 12 males; mean age: 61 years) with SE who received i.v. VPA as first-line therapy (25 mg/kg in 100 mL saline infused over 15 min). ECG tracing was monitored before, during, and after infusion. Liver function and serum ammonia tests were conducted after 24 and 72 h of treatment. We evaluate the response of SE to i.v. therapy and short-term outcome. RESULTS: In 15 out of 23 patients (65%), i.v. VPA was effective. In our population, we retrospectively identified three different subgroups: patients with cardiorespiratory comorbidities discouraging the use of traditional SE first-line drugs, patients with specific epileptic subsyndromes (such as idiopathic generalized epilepsy), and patients affected by psycho-organic syndromes. No significant adverse effects were detected. DISCUSSION: Our study shows the clinical relevance of i.v. VPA as first-line therapy of SE in patients with medical conditions contraindicating the use of traditional first-line antiepileptic drugs for SE, and in those presenting with specific forms of SE.

A differential color flicker test for detecting acquired color vision impairment in multiple sclerosis and diabetic retinopathy.

BACKGROUND: Optic neuritis related to multiple sclerosis and diabetic retinopathy are relatively selective post-retinal and retinal vision disorders. Vision impairment in both conditions is reliably measured by testing critical fusion frequency (CFF). METHODS: To examine color vision, we measured the CFF in response to red and blue stimuli, and tested CFF values in patients without evident vision impairment. To ensure that differences in CFF values in a given subject depended only on color perception we displayed red and blue flickering stimuli at equal luminance. CFF to red or blue stimuli were compared in patients with medical history of optic neuritis related to multiple sclerosis (post-retinal vision impairment), patients with diabetic retinopathy (retinal vision impairment) and healthy subjects. RESULTS: The test procedure disclosed altered CFF values for red and blue stimuli in both groups of patients studied. The comparison between the two groups disclosed a prevalent CFF impairment for red stimuli in patients with optic neuritis related to multiple sclerosis and for blue stimuli in patients with diabetic retinopathy. CONCLUSIONS: The differential color flicker test appears highly accurate in detecting color vision impairment. Comparison of the two color CFFs differentiates retinal from post-retinal visual disorders.

Metaplasticity of the human trigeminal blink reflex.

Although synaptic plasticity in the human cerebral cortex is governed by metaplasticity, whether a similar mechanism operates at brainstem level is unknown. In this study in healthy humans we examined the effects and interactions induced by pairing supraorbital nerve high-frequency electrical stimulation (HFS) protocols on the R2 component of the trigeminal blink reflex [Mao, J.B. & Evinger, C (2001) J Neurosci., 21:RC151(1-4)]. Changes in the R2 component were tested by pairing three different priming stimulation protocols inducing long-term potentiation (LTP)-like or long-term depression (LTD)-like effects (LTP-HFS and LTD-HFS), or no change (CONTROL-HFS) with a subsequent test LTP-HFS. Additionally, to examine changes in the R2 component induced by nonspecific factors, two CONTROL-HFS sessions were paired. Priming LTP-, LTD- or CONTROL-HFS potentiated, inhibited or left unchanged the area of the R2 component. Regardless of the type of priming LTP-, LTD- or CONTROL-HFS, the test LTP-HFS induced negligible differences in the R2 component. When two CONTROL-HFS sessions were paired, the test CONTROL-HFS increased the latency and markedly reduced the duration and area of the R2 component. The analysis of the normalized data across the first three experimental sessions, corrected for the inhibitory effects found in the fourth experiment, showed that the test LTP-HFS potentiated the R2 component area of the trigeminal blink reflex only when preceded by a priming LTD-HFS. We propose that homosynaptic metaplasticity might operate in the brainstem circuitry of the blink reflex.

Voluntary, spontaneous and reflex blinking in patients with clinically probable progressive supranuclear palsy.

Patients with progressive supranuclear palsy (PSP) often have blinking abnormalities. In this study we examined the kinematic features of voluntary, spontaneous and reflex blinking in 11 patients with PSP and healthy control subjects. Patients were asked to blink voluntarily as fast as possible; spontaneous blinking was recorded during two 60 s rest periods; reflex blinking was evoked by electrical stimulation of the supraorbital nerve. Eyelid movements were recorded with the SMART analyzer motion system. During voluntary blinking the closing and opening phases lasted longer in patients than in healthy subjects. Furthermore, the peak velocity of the closing phase of voluntary blinking was lower in patients than healthy subjects. During spontaneous blinking the blink rate was markedly lower in patients than in control subjects. Patient's recordings also showed kinematic abnormalities of spontaneous (reduced peak velocity of both closing and opening phases) and reflex (reduced peak velocity and increased duration of the opening phase) blinking. Recordings during reflex blinking disclosed an enhanced excitability of the interneuronal pool mediating the closing and opening blink phases. Finally, the pause, a neurophysiological marker of the switching processes between the closing and opening phases, was prolonged in all the three types of blinking. The abnormal kinematic variables correlated with patients' clinical and kinematic features. Abnormal voluntary, spontaneous and reflex blinking in patients with PSP reflects the widespread cortical, subcortical and brainstem degeneration related to this disease.

Ipsilateral sequential arm movements after unilateral subthalamic deep-brain stimulation in patients with Parkinson's disease.

Unilateral STN-DBS significantly improves the performance of contralateral sequential arm movements. Whether unilateral STN-DBS also improves ipsilateral sequential movement is unclear. In this study in unmedicated parkinsonian patients, we tested the effect of unilateral STN-DBS on the performance of ipsilateral sequential movements and compared it with the performance of contralateral sequential movements. Three-dimensional movements were recorded with the ELITE system and three kinematic variables were considered: total movement time (TMT), total inter-onset latency (IOL), and spatial accuracy. Unilateral STN-DBS significantly decreased TMT in the contralateral arm and only tended to do so also in the ipsilateral arm, whereas it significantly decreased IOL and worsened spatial accuracy only on the contralateral side. Before unilateral STN-DBS a positive correlation was present between the clinical impairment and the TMTs in the contralateral and ipsilateral sides. After unilateral STN-DBS the UPDRS scores improved in the contralateral and to a lesser extent also in the ipsilateral side. Correlation analysis between clinical and kinematic data showed no differences between the contralateral and ipsilateral sides. Our kinematic findings show that after STN-DBS parkinsonian patients' performance of a sequential motor task improves significantly on the contralateral but only tended to do so on the ipsilateral side. Ipsilateral changes can be explained by the observation that the output structures of the basal ganglia send large ipsilateral and less dense contralateral projections to the thalamus.

Voluntary, spontaneous, and reflex blinking in Parkinson's disease.

Blinking, a motor act consisting of a closing and an opening eyelid movement, can be performed voluntarily, spontaneously, and reflexly. In this study we investigated the kinematic features of voluntary, spontaneous, and reflex blinking in patients with Parkinson's disease (PD), OFF and ON dopaminergic treatment. Patients were asked to blink voluntarily as fast as possible. Spontaneous blinking was recorded for a minute during which the subjects just relaxed. Reflex blinking was evoked by electrical stimulation on the supraorbital nerve. Eyelid movements were recorded with the SMART analyzer motion system. Patients OFF therapy paused longer than controls during voluntary blinking but not during spontaneous and reflex blinking. The blink rate tended to be lower in patients OFF therapy than in controls and the spontaneous blinking had abnormally low amplitude and peak velocity. Finally, in patients OFF therapy the excitability of the neural circuit mediating the closing phase of the reflex blinking was enhanced. Dopaminergic treatment shortened the pause during voluntary blinking and increased the blink rate. In PD patients the longer pauses between the closing and opening phase in comparison to normal subjects, suggest bradykinesia of voluntary blinking. PD patients also display kinematic abnormalities of spontaneous blinking and changes in the excitability of the closing phase of reflex blinking.

Visual evoked potentials modulation during direct current cortical polarization.

Transcranial direct current stimulation (tDCS) at low intensity induces changes in cortical excitability that persist after polarization ends. The effects of anodal and cathodal polarization remain controversial. We studied changes in visual evoked potentials (VEPs) during and after anodal and cathodal tDCS by applying, in healthy volunteers, 1 mA polarization through surface electrodes placed over the occipital scalp (polarizing) and over the anterior or posterior neck-base (reference). We compared tDCS applied at two durations, 3 and 10 min and both polarities. We assessed VEP-P100 latencies and amplitudes in response to pattern-reversal checkerboard stimuli before, during, and after polarization. Anodal polarization reduced VEP-P100 amplitude whereas cathodal polarization significantly increased amplitude but both polarities left latency statistically unchanged. These changes persisted for some minutes after polarization ended depending on the duration of tDCS and on the contrast level of visual stimuli. tDCS-induced changes in VEPs seem to depend on the duration of polarization and type of visual stimuli used. The effects induced on visual cortical neurones during polarization are more consistent than the aftereffects. Studying these changes during polarization may therefore improve our understanding of these phenomena.

Vep latency: sex and head size.

OBJECTIVE: To investigate whether differences in visual evoked potential (VEP) latencies in a large sample of healthy subjects are influenced by different head size or sex or both. METHODS: Black-and-white pattern-reversal checkerboard VEPs at a frequency of 2c/deg. were recorded in a group of 54 normal subjects of both sexes (age 30.15+/-9.12 years). P100 latency was measured in all subjects and the data were analyzed in the whole sample and in a selected subgroup of subjects of both sexes with comparable head size. RESULTS: In the study group overall, the P100 latency was slightly shorter in females than males and this small difference reached only weak statistical significance (P<0.04) whereas head size differed significantly between sexes (females

The timing and intensity of transcranial magnetic stimulation, and the scalp site stimulated, as variables influencing motor sequence performance in healthy subjects.

OBJECTIVE: The increasing therapeutic use of transcranial magnetic stimulation (TMS) in disorders of cortical excitability raises the need for reliable stimulus variables. Stimulation of cortical motor areas influences motor programming and execution. We investigated the effects of TMS delivered over various cortical motor areas during the reaction time (RT) on the execution of sequential rapid arm movements in healthy subjects. METHODS: Subjects performed a five-submovement (S1-S5) motor sequence mainly involving upper limb proximal muscles. RT and movement time (MT) were measured. We delivered late (close to movement onset) and early (close to the go signal) TMS over the primary motor area (M1-FDI hot-spot for the first dorsal interosseus, M1-D hot-spot for the deltoid muscle), the premotor (PM) area, and the supplementary motor area (SMA), using subthreshold and suprathreshold intensity, single and triple pulses. RESULTS: The motor sequence showed a characteristic pattern of submovement duration, S2-S3-S4 being faster than S1 and S5. Late TMS prolonged RT only when high-intensity pulses were delivered over M1-FDI. Single- and triple-pulse TMS over M1-D or M1-FDI significantly prolonged MT with a dose-related effect. Suprathreshold triple-pulse TMS over the PM-but not over the SMA-also lengthened the MT but did not change RT. Early triple-pulse TMS reduced the RT independently from the stimulus intensity and scalp site. SMA and PM-but not M1-D-stimulation also reduced the MT. Single-pulse TMS over the SMA, despite being delivered through a double-cone coil, did not change RT or MT. CONCLUSIONS: TMS-induced changes in the kinematics of a sequential arm movement depend closely on the timing of TMS interference, the scalp site stimulated, and the intensity (and number) of stimuli delivered. Late TMS interference inhibits, whereas early interference facilitates, motor performance. The cortical motor region most sensitive to TMS-induced inhibition is that below the scalp site for M1-FDI. In contrast, TMS-induced facilitation has no strict topographic organization. Particularly for MT (although inhibitory and facilitatory effects both depend on stimulation at high intensities) intensity is less crucial than timing of interference and scalp site.