Stance Postural Strategies in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

INTRODUCTION: Polyneuropathy leads to postural instability and an increased risk of falling. We investigated how impaired motor impairment and proprioceptive input due to neuropathy influences postural strategies. METHODS: Platformless bisegmental posturography data were recorded in healthy subjects and patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Each subject stood on the floor, wore a head and a hip electromagnetic tracker. Sway amplitude and velocity were recorded and the mean direction difference (MDD) in the velocity vector between trackers was calculated as a flexibility index. RESULTS: Head and hip postural sway increased more in patients with CIDP than in healthy controls. MDD values reflecting hip strategies also increased more in patients than in controls. In the eyes closed condition MDD values in healthy subjects decreased but in patients remained unchanged. DISCUSSION: Sensori-motor impairment changes the balance between postural strategies that patients adopt to maintain upright quiet stance. Motor impairment leads to hip postural strategy overweight (eyes open), and prevents strategy re-balancing when the sensory context predominantly relies on proprioceptive input (eyes closed).

EEG mean frequency changes in healthy subjects during prefrontal transcranial direct current stimulation.

In this pilot study we evaluated electroencephalographic (EEG) mean frequency changes induced by prefrontal transcranial direct current stimulation (tDCS) and investigated whether they depended on tDCS electrode montage. Eight healthy volunteers underwent tDCS for 15 min during EEG recording. They completed six tDCS sessions, 1 wk apart, testing left and right direct current (DC) dipole directions with six different montages: four unipolar montages (one electrode on a prefrontal area, the other on the opposite wrist) and two bipolar montages (both electrodes on prefrontal areas), and a single sham session. EEG power spectra were assessed from four 1-min EEG epochs, before, during, and after tDCS. During tDCS the outcome variable, brain rate (fb), changed significantly, and the changes persisted for minutes after tDCS ended. With the DC dipole directed to the left (anode on the left prefrontal area or wrist), fb increased, and with the DC dipole directed to the right (anode on the right prefrontal area or wrist), fb decreased, suggesting asymmetric prefrontal cortex functional organization in the normal human brain. Anodal and cathodal effects were opposite but equally large. Gender left these effects unchanged.

Transcranial direct current stimulation modulates motor responses evoked by repetitive transcranial magnetic stimulation.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive techniques able to induce changes in corticospinal excitability. In this study, we combined rTMS and tDCS to understand possible interactions between the two techniques, and investigate whether they are polarity dependent. MATERIALS AND METHODS: Eleven healthy subjects participated in the study. Each patient underwent both anodal and cathodal conditioning tDCS in two separate sessions; brief 5 Hz-rTMS trains were delivered over the primary motor cortex at an intensity of 120% the resting motor threshold (RMT) before tDCS (T0), immediately after (T1) and 10 min after current offset (T2). We then analysed changes induced by cathodal and anodal tDCS on TMS variables. RESULTS: Our results showed that in both anodal and cathodal sessions, the motor evoked potential (MEP) amplitude increased significantly in size before stimulation (T0). Conversely, after anodal tDCS, the MEP facilitation measured at T1 and T2 was absent, whereas after cathodal tDCS it was preserved. CONCLUSIONS: Our findings provide new direct neurophysiological evidence that tDCS influences primary motor cortex excitability.

Topiramate and visual loss in a patient carrying a Leber hereditary optic neuropathy mutation.

We describe a 43-year-old patient who experienced visual loss 4 years after beginning antiepileptic therapy with topiramate. Ophthalmological and neurological examinations led to a preliminary diagnosis of bilateral toxic optic neuritis. Mitochondrial genome sequence analysis detected a Leber hereditary optic neuropathy 11778G>A mutation. The possibility that topiramate might favor a conversion disease, alerts physicians to seek a history of blindness in patients undergoing chronic antiepileptic therapy.

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.

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.

A biologically inspired neural network controller for ballistic arm movements.

BACKGROUND: In humans, the implementation of multijoint tasks of the arm implies a highly complex integration of sensory information, sensorimotor transformations and motor planning. Computational models can be profitably used to better understand the mechanisms sub-serving motor control, thus providing useful perspectives and investigating different control hypotheses. To this purpose, the use of Artificial Neural Networks has been proposed to represent and interpret the movement of upper limb. In this paper, a neural network approach to the modelling of the motor control of a human arm during planar ballistic movements is presented. METHODS: The developed system is composed of three main computational blocks: 1) a parallel distributed learning scheme that aims at simulating the internal inverse model in the trajectory formation process; 2) a pulse generator, which is responsible for the creation of muscular synergies; and 3) a limb model based on two joints (two degrees of freedom) and six muscle-like actuators, that can accommodate for the biomechanical parameters of the arm. The learning paradigm of the neural controller is based on a pure exploration of the working space with no feedback signal. Kinematics provided by the system have been compared with those obtained in literature from experimental data of humans. RESULTS: The model reproduces kinematics of arm movements, with bell-shaped wrist velocity profiles and approximately straight trajectories, and gives rise to the generation of synergies for the execution of movements. The model allows achieving amplitude and direction errors of respectively 0.52 cm and 0.2 radians. Curvature values are similar to those encountered in experimental measures with humans. The neural controller also manages environmental modifications such as the insertion of different force fields acting on the end-effector. CONCLUSION: The proposed system has been shown to properly simulate the development of internal models and to control the generation and execution of ballistic planar arm movements. Since the neural controller learns to manage movements on the basis of kinematic information and arm characteristics, it could in perspective command a neuroprosthesis instead of a biomechanical model of a human upper limb, and it could thus give rise to novel rehabilitation techniques.

Impairment in color perception in migraine with and without aura.

OBJECTIVE: To assess visual perception in 40 patients suffering from migraine with aura (MA), 40 patients suffering from migraine without aura (MO), and 40 controls. BACKGROUND: Visual perception abnormalities are a common feature in both MA and MO. METHODS: We performed luminance and color central perimetry. Black and white pattern reversal visual-evoked potentials were also assessed. RESULTS: Luminance perimetry was similar in patients and controls. Color perimetry instead revealed an impairment in the perception of red ("quantitative perception index") in migraine patients; this impairment was more pronounced in patients with MA (P < .001) than in those with MO (P < .05) and was related to the degree of photophobia recorded before testing. A subgroup of MO patients who had a migraine attack shortly after being tested also displayed a marked impairment in the perception of blue. This subgroup of patients had a statistically significant (P < .001) lower perception of blue than the rest of the MO patients, who had a migraine attack later; they also had a high degree of unpleasant perceptions after testing. Black and white visual evoked potentials were similar in patients and controls. CONCLUSION: The impairment in visual perception of red, which was more marked in MA than in MO patients, may be related to the degree of photophobia recorded before testing. The reduced perception of blue, which only occurred in a subgroup of MO patients in the premonitory phase of the migraine attack, probably occurs through mechanisms that involve dopaminergic function. We cannot exclude the possibility that the visual stimulations induced the migraine attack in this subgroup of MO patients shortly after they were tested.

Saliva and serum levetiracetam concentrations in patients with epilepsy.

Although antiepileptic drug (AED) monitoring in saliva may have some clinical applicability, it has not yet come into routine use. The correlation between levetiracetam (LEV) saliva and serum concentrations also remains unclear. To confirm LEV saliva assay as a useful, noninvasive alternative to serum measurement, we investigated the possible correlation between saliva and serum LEV concentrations. Samples of saliva and blood were collected from 30 patients with epilepsy receiving chronic therapy with LEV as monotherapy or add-on therapy, and LEV concentrations were assayed in saliva and serum. Linear regression analyses showed a close correlation between saliva and serum LEV concentrations (r2 = 0.90; P < 0.001). LEV blood and saliva concentrations were linearly related to daily drug doses (r2 = 0.78 and 0.70; P < 0.01). When data were analyzed for subgroups (patients receiving LEV in monotherapy, as add-on therapy with enzyme-inducer AEDs, and as add-on therapy with noninducer or moderate-inducer AEDs), no significant difference was found between saliva and serum LEV concentrations among groups. These preliminary results indicate that LEV, like other AEDs, can be measured in saliva as an alternative to blood-based assays. Saliva LEV collection and assay is a valid noninvasive, more convenient alternative to serum measurement.

A questionnaire study on knowledge of and attitudes toward epilepsy in schoolchildren and university students in Rome, Italy.

PURPOSE: To estimate the knowledge of and attitudes toward epilepsy in schoolchildren and university students in Rome. METHODS: We administered a custom-designed questionnaire in Italian on general knowledge, specific knowledge and social impact of epilepsy to a random sample of upper-middle class pupils and university undergraduate students in Rome. RESULTS: The young people we studied have a reasonable knowledge of epilepsy: as many as 91% claimed to know something about the disease. Yet only 16% correctly stated the prevalence as being about 1 in 100. Middle-school pupils and university graduates consider epilepsy as an illness from which patients rarely recover and one that creates problems in finding employment. The largest number of correct answers for nearly all the questionnaire items came from university students. CONCLUSIONS: These findings suggest that apart from an encouragingly large number of the subjects we studied claim to know something about epilepsy (91% today versus 73% 22 years ago), Italian students still know little about epilepsy. These preliminary data should provide a starting point for a future in-depth population-based survey and information campaigns at schools in the Rome metropolitan area.

The blink reflex in "chronic migraine".

OBJECTIVES: Activation of the trigeminovascular system and sensitisation of brainstem trigeminal nuclei are thought to play an important role in migraine. The aim of this study was to investigate the blink reflex and its habituation in patients with "chronic migraine". METHODS: We studied 35 patients suffering from "chronic migraine" (IHS classification criteria) outside and during a spontaneous attack, and 35 control subjects. An EMG device with a specific habituation test program was used to elicit and record blink reflex responses and to randomly repeat stimulations at different time intervals so as to induce habituation. RESULTS: The R(1) and R(2) latencies, amplitudes and areas of the basal blink reflex were similar in patients studied both outside and during an attack as well as in control subjects, whereas the blink reflex habituation responses were markedly reduced in patients studied outside an attack. The percent changes in the R(2) areas from the baseline values, obtained when stimuli were delivered at time intervals of 10, 5, 4, 3, 2 and 1s, were statistically different (p<0.01-p<0.001) from those of the same patients studied during a migraine attack and of those of control subjects. There was a significant correlation between decreased habituation of the blink reflex and a higher frequency of attacks. The stimulus intensities of the blink reflex (multiples of the detection threshold intensities) were significantly lower (p<0.001) on the side affected, or more severely affected, by headache in patients studied during a migraine attack. CONCLUSIONS: The decreased habituation of the blink reflex outside an attack reflects abnormal excitability in "chronic migraine", which normalizes during the attacks. The inverse correlation between the frequency of attacks and habituation responses confirms the abnormal excitability induced by the high frequency of attacks. Central sensitisation mechanisms (allodynia) may explain the lower detection thresholds observed on the side affected by headache in patients during the attacks. SIGNIFICANCE: The blink reflex and its habituation may help shed light on the subtle neurophysiological changes that occur in migraine patients between and during attacks.

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

Difference in sensorimotor adaptation to horizontal and vertical mirror distortions during ballistic arm movements.

When learning a novel motor task, the sensorimotor system must develop new strategies to efficiently control the limb(s) involved, and this adaptation appears to be developed through the construction of a behavioral map known as an 'internal model'. A common method to uncover the mechanisms of adaptation and reorganization processes is to expose the system to new environmental conditions, typically by introducing visual or mechanical distortions. The present study investigated the adaptation mechanisms of the human sensorimotor system to horizontal and vertical mirror distortions (HMD and VMD) during the execution of fast goal-directed arm movements. Mirror distortions (MDs) were created by means of virtual visual feedback on a computer screen while the movement was executed on a graphics tablet. Twenty healthy adult participants were recruited and assigned to one of two groups of 10 people each. Tests were divided in two subsequent blocks of five trials. The first block consisted of trials with no mirror distortion (NMD), while the second block was recorded when exposing one group to HMD and the other to VMD. Both MDs resulted in kinematic changes: during the tests with the MDs the participants did not reach the performance level found at the NMD test. Motor performance during HMD appeared to be globally better than during VMD and the adaptation process to VMD appeared to be slower than to HMD, but data interpretation was hampered by large within-participant and between-participant variability. In-depth analyses of the data revealed that most of the motor performance information was contained in the direction of movement. The data supported the idea that the internal model for HMD was already partially built.

High prevalence of spontaneous portal-systemic shunts in persistent hepatic encephalopathy: a case-control study.

Large spontaneous portal-systemic shunts have been occasionally described in patients with cirrhosis. This study was undertaken to assess the prevalence of portal-systemic shunts in patients with cirrhosis with recurrent or persistent hepatic encephalopathy (HE) as compared with patients with cirrhosis without HE. Fourteen patients with cirrhosis with recurrent or persistent HE (cases) and 14 patients with cirrhosis without previous or present signs of overt HE matching for age and degree of liver failure (controls) were studied. Each patient underwent neurological assessment and cerebral magnetic resonance (MR) imaging to exclude organic neurological pathological conditions. HE evaluation included psychometric performance (Trail-Making Test A), electroencephalogram (EEG), mental status examination and grading, arterial, venous, and partial pressure of ammonia determination. The presence of portal-systemic shunts was assessed by portal venous phase multidetector-row spiral computed tomography (CT). Large spontaneous portal-systemic shunts were detected in 10 patients with HE and in only 2 patients without HE (71% vs. 14%; chi square = 9.16; df = 1.0; P = .002). The patients with HE presented ascites (P = .002) and medium/large esophageal varices (P = .02) less frequently than the control group. In conclusion, our study suggests that large spontaneous shunts may often sustain the chronicity of HE; the presence of large shunts should be sought in patients with cirrhosis with recurrent or persistent HE.

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.

Clinical, cognitive, and neurophysiologic correlates of short-term treatment with carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers.

BACKGROUND: The adverse effects of the antiepileptic drugs (AEDs) originally developed are well known, while those of the newer AEDs remain unclear. OBJECTIVE: To investigate clinical, cognitive, and neurophysiologic effects of carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers. METHODS: A double-blind crossover study was conducted in 10 volunteers. Eight-day treatment with carbamazepine, oxcarbazepine, levetiracetam, or placebo was administered in random order. Drug doses were titrated gradually to the daily target doses on day 7: carbamazepine 800 mg, oxcarbazepine 1200 mg, and levetiracetam 1500 mg. At baseline and at the end of each treatment period, participants underwent cognitive and neurophysiologic assessment. A washout period of 14 days between treatment periods was conducted. RESULTS: More adverse events were self-reported with carbamazepine (63%) than the other treatments (oxcarbazepine 12%, levetiracetam 20%, placebo 5%; p < 0.001 between the 4 groups). Carbamazepine induced the greatest motor slowing (p = 0.002), followed by oxcarbazepine (p = 0.01). Levetiracetam left baseline motor speed unchanged. All AEDs increased attention span from baseline values as shown on the Stroop test. Quantitative electroencephalogram (EEG) analysis showed that carbamazepine significantly increased the delta-theta power and reduced the frequency of alpha rhythm; oxcarbazepine induced smaller changes than carbamazepine. Levetiracetam did not change any EEG measurements. On color visually evoked potential (VEP) tests, carbamazepine induced a constant slowing of P1 latency, while oxcarbazepine induced changes only after the blue-black pattern. All color VEP measures for volunteers receiving levetiracetam were almost unchanged. CONCLUSIONS: After short-term treatment in healthy volunteers, carbamazepine induced major clinical and neurophysiologic changes. Oxcarbazepine was better tolerated than carbamazepine. Levetiracetam interfered least with clinical and neurophysiologic test results.

Decreased habituation of the R2 component of the blink reflex in migraine patients.

OBJECTIVE: Activation of the trigemino-vascular system as well as of brainstem trigeminal nuclei are thought to play an important role in migraine. The aim of this study was to investigate the habituation phenomenon of the blink reflex in 30 headache-free migraine patients and 30 control subjects. METHODS: An electromyographic device with a specific habituation test program was used to elicit and record blink reflex responses on both the right and left sides, and to randomly repeat the stimulations at different time intervals in order to induce habituation. RESULTS: Whereas the R1 and R2 latencies, amplitudes and areas in the basal assessment were similar in patients and control subjects, the blink reflex habituation responses were markedly reduced in migraine patients who had a migraine attack within 72 h after testing (group A). In these patients, the differences between the R2 areas, obtained when stimuli were delivered at subsequent time intervals ranging between 10-5, 5-4, 4-3 and 3-2 s, were statistically different (P<0.001) from those of the patients who had a migraine attack after a longer time interval (group B) and control subjects. CONCLUSIONS: Our data suggest that the brainstem pathways involved in the blink reflex may be activated in the premonitory phase of migraine attacks, probably through mechanisms that involve dopaminergic function.