High-resolution ultrasound changes of the vagus nerve in idiopathic Parkinson's disease (IPD): a possible additional index of disease.

BACKGROUND AND RATIONALE: Histopathological studies revealed degeneration of the dorsal motor nucleus of the vagus nerve (VN) early in the course of idiopathic Parkinson's disease (IPD). Degeneration of VN axons should be detectable by high-resolution ultrasound (HRUS) as a thinning of the nerve trunk. In order to establish if the VN exhibits sonographic signs of atrophy in IPD, we examined patients with IPD compared with age-matched controls. MATERIAL AND METHODS: We measured the caliber (cross-sectional area, CSA) and perimeter of the VN in 20 outpatients with IPD (8 females and 12 males; mean age 73.0 + 8.6 years) and in age-matched controls using HRUS. Evaluation was performed by blinded raters using an Esaote MyLab Gamma device in conventional B-Mode with an 8-19 MHz probe. RESULTS: In both sides, the VN CSA was significantly smaller in IPD outpatients than in controls (right 2.37 + 0.91, left 1.87 + 1.35 mm2 versus 6.0 + 1.33, 5.6 + 1.26 mm2; p <0.001), as well as the perimeter (right 5.06 + 0.85, left 4.78 + 1.74 mm versus 8.87 + 0.86, 8.58 + 0.97 mm; p <0.001). There were no significant correlations between VN CSA and age, the Hoehn and Yahr scale, L-dopa therapy, and disease duration. CONCLUSION: Our findings provide evidence of atrophy of the VNs in IPD patients by HRUS. Moreover, HRUS of the VN represent a non-invasive easy imaging modality of screening in IPD patients independent of disease stage and duration and an interesting possible additional index of disease.

Motor and somatosensory evoked potentials in Autosomal Dominant Hereditary Spastic Paraparesis (ADHSP) linked to chromosome 2p, SPG4.

The aim of our study was to evaluate Motor Evoked Potentials (MEPs) and cortical excitability, using Transcranial Magnetic Stimulation (TMS) as well as short latency Somatosensory Evoked Potentials (SEPs) in Autosomal Dominant Hereditary Spastic Paraparesis (ADHSP) patients. MEPs were recorded from upper and lower limb muscles in 12 patients (7 m and 5f) affected by ADHSP with spastin mutation (SPG4). We measured: (i) motor threshold (MTh); (ii) total motor conduction time (TMCT); (iii) direct and indirect central motor conduction time (d-CMCT and i-CMCT) calculated by subtracting from the cortical latency those obtained on magnetic spinal stimulation (d-PMCT) and via the F-wave method (i-PMCT); (iv) MEP amplitude (MEP/Mmax ratio%) and (v) duration of the cortical silent period (CSP). Latency, amplitude and persistence of the F-wave obtained with electrical nerve stimulation were also considered; H reflex was also tested from lower extremities. SEPs were recorded from spine and scalp sites following median and posterior tibial nerve stimulation; conventional latency and amplitude measurements were performed. In a comparison with the control group, the MTh recording from lower limbs was significantly higher (67.5 +/- 7.7% versus 52.5 +/- 6.9%), MEPs were absent in one case and showed reduced amplitude in the remainders (22.9 +/- 12.6% versus 66.3 +/- 25.9% of M wave); TMCT resulted to be abnormal (36.5 +/- 3.9 ms versus 27.1 +/- 1.4 ms) and d-CMCT as well as i-CMCT were significantly prolonged (23.1 +/- 3.5 ms versus 13.8 +/- 1.3 ms; and 20.1 +/- 3.4 ms versus 10.6 +/- 1.3 ms, respectively). The CSP, which was normal from the hands, was significantly shortened from the legs and correlated with spasticity scoring (Ashworth scale). Cortical SEPs from lower limbs were abnormal in all cases, whereas SEPs by stimulation of median nerves were normal; F-wave parameters from upper limbs showed no abnormalities, whereas an increased persistence was detected from lower limbs; H reflex amplitudes resulted larger compared with controls. Moreover, shortening of the CSP, being correlated with the Ashworth scale, can be considered an electrophysiological marker of spasticity that seems to arise from impairment of the supraspinal or intracortical inhibitory pathways with an additional contribution of increased segmental motor neuron excitability. These data prove the existence of comparable neurophysiological abnormalities in ADHSP with spastin mutation (SPG4) when long ascending and descending pathways are involved.

Mismatch negativity analysis in drug-resistant epileptic patients implanted with vagus nerve stimulator.

It is well known that some epileptic patients does not respond to conventional treatments, despite multiple combination of antiepileptic drugs, and they are therefore considered drug-resistant. For these patients, vagal nerve stimulation (VNS) represents a successful alternative to traditional therapy, and it is generally well tolerated; beside benefits on seizure frequency, VNS showed positive effects on cognition and mood. Aim of this study was to investigate short-term memory changes in a group of 12 patients implanted with VNS, through Mismatch Negativity wave (MMN). After 1 year of follow-up, MMN latencies and amplitudes did not show significant changes following VNS implantation, independently on current intensity, as compared with pre-implantation values. In two patients, MMN values, which were abnormal before VNS implantation, showed a major reduction in latency and an increase in amplitude after implantation, suggesting a likely positive effect of VNS on pre-attentive processes investigated by MMN.

A low-cost interface for control of computer functions by means of eye movements.

Human-computer interactions (HCI) have become an important area of research and development in computer science and psychology. Appropriate use of computers could be of primary importance for communication and education of those subjects which could not move, speak, see or hear properly. The aim of our study was to develop a reliable, low-cost and easy-to-use HCI based on electrooculography signal analysis, to allow physically impaired patients to control a computer as assisted communication. Twenty healthy subjects served as volunteers: eye movements were captured by means of four electrodes and a two-channel amplifier. The output signal was then transmitted to an "Analog to Digital" (AD) converter, which digitized the signal of the amplifier at a rate of 500 Hz, before being sent to a laptop. We designed and coded a specific software, which analyzed the input signal to give an interpretation of eye movements. By means of a single ocular movement (up, down, left and right) the subjects were then able to move a cursor over a screen keyboard, passing from one letter to another; a double eye blink was then necessary to select and write the active letter. After a brief training session, all the subjects were able to confidently control the cursor and write words using only ocular movements and blinking. For each subject we presented three series of randomized words: mean time required to enter a single character was about 8.5s, while input errors were very limited (less than 1 per 250 characters). Our results confirm those obtained in previous studies: eye-movement interface can be used to properly control computer functions and to assist communication of movement-impaired patients.

Quantitative EEG analysis in post-traumatic anosmia.

Many objective and quantitative methods have been developed to create a procedure or a device to prove, describe and quantify olfactory deficit and anosmia, especially after a head trauma. Electrophysiological testing throughout olfactoelectroencephalography (olfactoEEG) is based on brain activity desynchronisation, and on the subsequent disappearance of alpha activity on the posterior regions after an olfactory stimulus. Yet traditional evaluation of EEG can be difficult, because of little or hardly detectable alpha activity on the posterior regions ('alpha rare'). The aim of this study was to evaluate the Olfactory Stop Reaction (OSR) by means of frequency band power calculation and subsequent topographical mapping in patients with post-traumatic anosmia, who presented 'alpha rare' EEG. Twenty-five consecutive patients, affected by anosmia caused by head trauma, were submitted to an EEG recording with olfactory stimulation. After signal processing and analysis, an Olfactory Stop Reaction was detected in 17 out of 25 patients; moreover, in these patients we detected a significant decrease in alpha band power in the occipital regions and an increase in theta band power on midline frontal and central regions after olfactory stimulation. In the remaining eight patients, no significant variation in band power was observed. In conclusion, an objective evaluation of the olfactory function with this method of automatic EEG signal analysis allows the limits given by psychophysical methods and traditional EEG to be overcome and attempts to fulfil the requirements for standardization of olfactory function evalution.

Visual-evoked potentials to onset of chromatic red-green and blue-yellow gratings in Parkinson's disease never treated with L-dopa.

The differential dysfunction of chromatic and achromatic visual pathways in early Parkinson's disease (PD) was evaluated by means of visual-evoked potentials (VEPs) recorded in 12 patients (mean age 60.1 +/- 8.3 years; range 46 to 74 years) in the early stages of PD and not yet undergoing treatment with L-dopa, and in 12 age-matched controls. Visual stimuli were full-field (14 deg) equiluminant red-green (R-G), blue-yellow (B-Y), and black-white (B-W) sinusoidal gratings of two cycles per degree, presented in onset (300 milliseconds)--offset (700 milliseconds) mode, at two contrast (K) levels (90% and 25%). The VEP mean latencies were significantly more delayed in PD patients than in controls for chromatic than for luminance stimuli, in particular for B-Y stimuli of low contrast (K90%: B-W = 6.6 milliseconds, R-G = 3.34 milliseconds, B-Y = 15.48 milliseconds; K25%: B-W = 7.8 milliseconds, R-G = 14.8 milliseconds, B-Y = 28.9). Latencies of chromatic VEPs were more variable that achromatic VEP latencies in both normal subjects and PD patients. Therefore, the frequency of latency abnormalities (within 30%) was not significantly different for the three visual stimuli. Our results show that, in addition to achromatic VEPs, chromatic VEPs are impaired in early PD patients not yet undergoing L-dopa therapy, indicating an acquired color deficiency in these patients. The greater delay for the B-Y VEPs suggests a higher vulnerability of visual blue-cone pathway in the early stages of the disease. However, the overall sensitivity of chromatic VEPs in detecting early visual impairment in PD is comparable with that of achromatic VEPs.

Characteristics of cerebral microembolism during carotid stenting and angioplasty alone.

BACKGROUND: Cerebral microembolism has often been documented by transcranial Doppler imaging during carotid angioplasty and stenting. However, few data are available about its characteristics during the 2 different kinds of procedure. OBJECTIVES: To compare the incidence of microemboli occurring during angioplasty alone with that during stenting in the different phases of the procedures and to relate it to periprocedural cerebrovascular complications. PATIENTS AND METHODS: Thirty-eight patients underwent 41 procedures (15 angioplasty alone and 26 stenting) for symptomatic carotid stenoses of 70% or more. Transcranial Doppler monitoring was performed to detect microemboli in the middle cerebral artery during 3 phases of the procedure: (1) guidewire crossing, (2) first dilatation in case of angioplasty alone or stent release with predilatation if performed, and (3) further dilatation. RESULTS: Microemboli occurred in all cases in phase 1 of the procedure but less frequently in the arteries treated with stenting when compared with those treated with angioplasty alone in phase 2 and particularly (P<.02) in phase 3. The mean number of microemboli was highest in phase 2, predominant (P<.05) during angioplasty alone, and particularly reduced (P<.02) in phase 3 during the stenting procedures. During 2 (5%) of the 41 procedures, cerebrovascular complications occurred in phase 1, with the number of microemboli being higher than mean values. CONCLUSIONS: Cerebral microembolism is a very common event, especially during guidewire crossing and angioplasty alone compared with stenting. Further studies concerning the prognostic significance of this are advisable.

Mitochondrial tRNA(Cys) gene mutation (A5814G): a second family with mitochondrial encephalopathy.

We report an Italian family with maternally inherited encephalomyopathy including progressive external ophthalmoplegia, seizures, and neurophysiological evidence of brainstem dysfunction. Mitochondrial DNA analysis showed a heteroplasmic point mutation at position 5814 in the tRNA gene for cysteine (A5814G), previously reported in a 5-year-old girl of Portuguese origin. The mutation was very abundant (> 95%) in both muscle and blood from the proposita and was present in lower proportions (average 85 +/- 6%) in blood from three less severely affected maternal relatives. This observation confirms pathogenicity for the A5814G mutation.

Changes in pain perception and pain-related somatosensory evoked potentials in humans produced by exposure to oscillating magnetic fields.

Nociception has been reported to be influenced by exposure to magnetic fields (MFs). The aim of this study was to investigate the effects of 2 h exposure to weak, oscillating MFs on pain perception thresholds and on pain-related somatosensory evoked potentials (SEPs). In 11 healthy volunteers, pain perception thresholds and pain-related SEPs were assessed by intracutaneous electrical stimulation. After sham treatment, pain thresholds significantly increased, whereas after MFs a slight non-significant decrease in thresholds was found. After both treatments pain-related SEP amplitude was reduced, but this decrease was more evident and statistically significant only after MF exposure. The increase found in thresholds after sham exposure may be due to stress-induced analgesia (SIA) and the contrasting behaviour recorded after MF exposure might indicate a suppression of SIA. The significant reduction in pain-related SEP amplitude observed after MF exposure provides the first evidence that human SEPs are influenced by MFs.

Normative data for onset VEPs to red-green and blue-yellow chromatic contrast.

OBJECTIVE: To better characterize the properties of chromatic VEPs to onset-offset of red-green and blue-yellow equiluminant patterns, and establish normative values for a set of stimuli able to elicit robust and reliable responses, suitable for the clinical application. METHODS: Chromatic VEPs have been recorded (Oz lead) from 28 normal subjects (age range 20-53 years) in response to monocular presentation of both red-green and blue-yellow equiluminant sinusoidal gratings. Stimuli were generated by a Cambridge VSG/2 card and displayed on a Barco CCID monitor (14x14 deg field size). Spatial frequency, chromaticity, contrast and onset-offset duration were varied. RESULTS: For both red-green and blue-yellow equiluminant stimuli, robust responses have been obtained with gratings of 2 c/deg, presented in onset (300 ms) offset (700 ms) mode, at contrasts ranging from 90 to 6%. In all observers, the VEP waveform consisted mainly of a negative wave at stimulus onset, with a latency rapidly increasing with decreasing contrast. For both red-green and blue-yellow stimuli, the VEP contrast threshold coincided with the psychophysical threshold. CONCLUSIONS: The results complement previous studies aimed at characterizing the properties of chromatic VEPs. In addition, normative data are provided for a set of stimulus characteristics suitable for the clinical routine.

Changes in long-latency reflexes onset latencies across full-wave rectified and non-rectified recordings.

Electrically elicited long-latency reflexes (LLRs) were obtained from thenar muscles by either fully rectified or non-rectified raw recordings in 10 healthy volunteers. The LLR II onset latencies were significantly (P < 0.0001) delayed on rectified (mean +/- SD: 49.8+/-2.9 ms) compared to raw (45.3+/-2.3 ms) recordings, with a mean difference of 4.4 ms. These data show that, according to the recording technique employed, the LLR II onset latencies can change considerably. The possible implications on cortical relay time (CRT) calculation and the understanding of the intracortical connections physiology are discussed.

Cortical silent period in patients with amyotrophic lateral sclerosis.

Transcranial magnetic stimulation (TMS) during a muscle contraction induces a motor-evoked potential (MEP) in the skeletal muscle followed by a cessation of EMG activity, the cortical silent period (C-SP). The C-SP is a useful parameter to indicate the activation of the motor system. Accurate determination of the C-SP can be important in amyotrophic lateral sclerosis (ALS), a progressive disorder of unknown etiology characterised by degeneration of upper and lower motor neurons. The aim of this study was to evaluate the sensitivity of C-SP as an index of motor system involvement, in ten patients affected by ALS, with a mean duration of the disease: 5. 5+/-3.4 months, by means of an objective computer-aided method to measure C-SP and its relationship to stimulation intensity. C-SP duration was significantly reduced in ALS patients compared to controls at low stimulation intensity corresponding to an MEP threshold increased by 15%. While in less severely affected patients C-SP duration approached control values at higher stimulation intensities (25 and 50% upper MEP threshold), in more severe ALS subjects it showed a further reduction, allowing them to be discriminated.

Vestibular-evoked myogenic potentials: a method to assess vestibulo-spinal conduction in multiple sclerosis patients.

Vestibular-evoked myogenic potentials (VEMPs), elicited by acoustic stimulation, have been proposed in the assessment of the vestibulo-cervical reflex pathways. The procedure has been previously validated in several otovestibular disorders. The aim of this study was to investigate patients affected by multiple sclerosis (MS) in the attempt to clarify the underlying physiopathogenetic mechanisms and the clinical utility of VEMPs in detecting vestibulospinal involvement in this disease. VEMPs were obtained according to the technique described by Colebatch and Halmagyi [Neurology 42 (1992) 1635]. We averaged the surface tonic electromyogram from right and left sternocleidomastoid muscle, after bilateral click stimulation (click duration 0.1 ms, repetition rate 3 Hz, intensity 140 dBSPL, 256 stimuli, repeated at least twice). In all cases, we obtained the biphasic, initially positive, p13-n23 wave pattern. P13 peak latency was bilaterally or unilaterally delayed in 8 out of 15 patients (mean delay: 2.2 ms; p < 0.01 on right and <0.05 on left side) and peak-to-peak amplitude significantly reduced (mean amplitude loss: 130 microV; p < 0.01 on right and <0.05 on left side). Their overall diagnostic yield resulted in 60%. In conclusion, the present findings prove that VEMPs are delayed in p13 component and altered in amplitude in MS patients. We hypothesise that these changes might be the result of a conduction impairment in vestibulo-spinal fibres, producing a morphologic alteration of the myogenic responses.

Equiluminant red-green and blue-yellow VEPs in multiple sclerosis.

The primate visual system is composed by two color-opponent pathways--red-green (R-G) and blue-yellow (B-Y)--subserved by the so-called parvo- and koniocellular streams respectively. The authors' aim was to compare the relative involvement of chromatic visual subsystems in multiple sclerosis (MS). In 30 MS patients with different forms of MS they recorded visual evoked potentials (VEPs) to onset (300 msec) and offset (700 msec) of equiluminant R-G and B-Y sinusoidal gratings of different contrast (90% and 25%). Equiluminance was established psychophysically by establishing the R-G and the B-Y color ratio at which chromatic gratings alternating at 15 and 10 Hz respectively had minimum visibility. The negative wave at stimulus onset with a peak latency of 120 to 160 msec was evaluated. Ordinary VEPs to luminance (LUM) contrast (black-white reversing checkerboards of 15' check size and 50% contrast) were also recorded for comparison. Latencies of R-G VEPs were abnormal in 53.3% and 58.3% of patients at 90% and 25% contrast respectively, whereas abnormal B-Y VEPs were 56.6% and 48.3%. Latencies of LUM VEPs were abnormal in 45% of patients. Interocular latency asymmetries were abnormal in 59.2% and 33.3% of patients for R-G, and 51.8% and 62.9% for B-Y. Latency asymmetries for LUM VEP were abnormal in 46.4% of patients. The higher rate of VEP abnormalities found with equiluminant chromatic stimuli compared with achromatic stimuli confirms the general vulnerability of color-opponent visual pathways in MS, even if the number of patients with abnormal findings was not significantly different when both test conditions were compared. VEPs to R-G and B-Y equiluminant stimuli appear to be involved approximately to the same extent.

Cryoglobulinemic peripheral neuropathy: neurophysiologic evaluation in twenty-two patients.

The aim of this study was to evaluate the frequency and degree of peripheral neuropathy in 22 consecutive patients with mixed cryoglobulinemia, whether symptom-free or with subjective neurological symptoms. Electrophysiological investigations were carried out and a biopsy of the sural nerve was performed in six patients. Peripheral neuropathy of the lower limbs was demonstrated, which was mostly sensory and light or moderate in 86% of cases (19 patients). F-Wave and H-reflex recordings were found to be the most reliable methods; in 77% of cases, they were abnormal (17 patients). Using somatosensory evoked potentials, we were able to exclude simultaneous central nervous system involvement in 10 patients.

The evaluation of sellar region tumours with pattern visual evoked potentials.

Pattern visual evoked potentials (PVEPs) were performed on 20 patients with sellar tumours. The aim was to assess the validity of full-field PVEPs combined with a topographic recording in chiasmatic compression. They were abnormal in 95% of the patients, with variable patterns (absent or distorted responses). Our results show that PVEPs are very sensitive in revealing compression on visual pathways and that they correlate with the progression of the tumour. However, they are not reliable in detecting the chiasmatic or retrochiasmatic site of the lesion and relative visual field defect, because of the multidirectional extension of the tumour.

Trigemino-cervical reflex in pathology of the brain stem and of the first cervical cord segments.

The trigemino-cervical reflex (CR) sensitivity and specificity in the assessment of cervico-bulbar lesions was evaluated in eleven selected subjects (4 multiple sclerosis, 3 tumoural processes and 4 cervical cord spondilogenetic myelopathies). Results were compared with those obtained from others neurophysiological investigations (EMG and blink-reflex) and with neuroimaging findings. Significant abnormal responses of CR were found in all patients varying from absent responses, to delayed or reduced amplitude patterns. These data stress the utility of CR in the check of cervico-bulbar lesions, where it can be considered complementary to other electrophysiological tests.

[Personal clinical and neurophysiological experience in the surgically treated carpal tunnel syndrome]. / La nostra esperienza clinica e neurofisiologica sulla sindrome del canale del carpo trattata chirurgicamente.

In 18 cases of carpal tunnel syndrome treated by surgical decompression of the median nerve, a neurophysiological control was performed before and after surgery. In all cases improvement or disappearance of the pain was observed; improvement in motor function was less constant. Control of the median nerve conduction showed that in all cases with preoperative distal latency less than 6 msec. there was a normalization of the nerve conduction after only 3 months. In cases of distal latency over 6 msec, and especially in those with complete motor conduction block, the latency remain within patological limits even 15 months after surgery. This may be explained either by a slower conduction of the regenerated fibres or by a persistent myelinic and axonal damage of the nerve.

[Clinical manifestations of spasmophilia in developing age]. / Le manifestazioni cliniche della spasmofilia in età evolutiva.

82 children (47 male and 35 female), aged between 2 and 12 years, with signs and symptoms consistent with spasmophilia, were investigated with an emg technique to better define boundaries of tetanic syndrome. In all subjects an ischaemic test was performed to the upper limb and the spontaneous emg activity from thenar eminence was recorded both during and after ischaemia. Moreover a clinical examination, with particular attention to objective signs of spasmophilia, were performed and serum electrolytes determined. Electromyographic spontaneous activity was noticed in 46 children (24 female, 22 male), 31 of them were hypocalcemic. The frequency of the various clinical manifestations is reported and correlated with emg and humoral findings. Significant difference between sexes in the incidence of tetanic syndrome where not noticed. More frequent symptoms for spasmophilia are tensive headache and cramps, abdominal spasms, psycomotos instability and anxiety; Chvostek's sign is frequent but no specific. The other symptoms assume relevance only if present in association. The role of electromyographic criteria in the detection of tetanic syndrome is stressed.

Transcallosal inhibition dampens neural responses to high contrast stimuli in human visual cortex.

Visual cortical areas in the two hemispheres interact via the corpus callosum, but the precise role of the callosal pathway in visual processing remains controversial. Here we have investigated the function of transcallosal projections in human primary visual cortex (V1). Visual evoked potentials (VEPs) triggered by grating stimuli of different contrasts were recorded before and after functional inactivation of the occipital cortex of one hemisphere via off-line low-frequency repetitive transcranial magnetic stimulation (rTMS; 0.5 Hz stimulation for 20 min). VEPs were recorded in V1 before (T0), immediately after (T1) and 45' following the completion of rTMS (T2). We found that low-frequency rTMS had an inhibitory effect on VEPs amplitudes at all contrasts in the treated side. Remarkably, reduction of VEP amplitudes in the inhibited hemisphere at T1 was accompanied by an increase in VEP amplitudes in the contralateral side only at mid-high contrasts (50-90%). This disinhibitory effect was observed with both central and hemifield stimulation. No changes in VEP amplitudes were observed when rTMS was applied to a cortical site more anterior with respect to V1. These data provide the first evidence that a mechanism of transcallosal inhibition dampens neural responses at high contrasts in human visual cortex.