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.

Retinocortical gain in the foveal pathway: the effect of spatial frequency and stimulus size.

The amplitude and the phase of the simultaneously recorded steady-state pattern electroretinogram (PERG) and visual evoked potential (VEP) were evaluated in humans as a function of the vertical diameter (D) of unidimensional Gabor stimuli. In the other dimension, parallel to the horizontal gratings, the patterns all had constant diameter (see Methods and Materials). Spatial frequencies (SFs) of 1 cycle per degree (cpd) and 5.3 cpd were counterphase modulated at a rate of 6.8 Hz. After off-line artifact rejection, the response was subject to Fast Fourier Transformation (FFT). Amplitude and phase of the first and second harmonics of both ERG and VEP were displayed for each SF and stimulus diameter. Both ERG and VEP amplitude were found to increase as a function of D. Using trend analysis we found that ERG amplitude increased linearly as a function of D. VEP amplitude was found to be both linear and cubic, as a function of D. We calculated the ratio of VEP amplitude and ERG amplitude at each D and termed it retinocortical gain (G). G normalized to stimulus area was high for small D and decreased with D independently of SF. Unity gain occurred at stimulus sizes of 6 degrees to 7 degrees. ERG phase was found to be more negative at 5.3 cpd than at 1 cpd. Although no significant difference was found between VEP phases at the two SFs tested, neither ERG nor VEP phase changed as a function of D. The results suggest that retinocortical gain is highest for the foveally centered low spatial frequency small patch Gabors. The results provide support for the notion of the "foveal window" in human vision.

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.

Amplitude loss of electrically and magnetically evoked sympathetic skin responses in early stages of type 1 (insulin-dependent) diabetes mellitus without signs of dysautonomia.

The sympathetic skin responses following both electrical nerve (eSSRs) and magnetic (mSSRs) brain stimulations have been investigated in 19 insulin-dependent diabetic patients with no evidence of a peripheral neuropathy or dysautonomia and compared to those obtained in 10 age-matched healthy subjects. SSR was recorded from the right hand and foot, controlateral to the stimulated side. The main findings were amplitude loss and disappearance of the eSSR in 12/19 (63.2%) and 11/19 (57.9%) patients, occurring more frequently than the mSSR; 7/19 (36.8%) and 5/19 (26.3%) were recorded from the hand and foot, respectively. The SSR to electrical stimulation was significantly reduced in the upper and lower extremities (p < 0.0001) compared to control results, whereas latencies were normal to both stimulation modalities. Only in two cases the responses were absent from the foot, one following electrical stimulation and the other after magnetic stimulation. No correlation was found between the SSR and metabolic indexes of diabetes mellitus or conduction velocity studies. On the basis of these data an early impairment of afferent pathways may be postulated.

Electrophysiological evidence for visuocognitive dysfunction in younger non Caucasian patients with Parkinson's disease.

A study of "primary" (VEPs) and "cognitive" (ERPs) visual evoked potentials was carried out in a group of non-demented Afro-American Parkinson's disease (PD) patients. Current studies suggest that differences exist in the clinical manifestations of PD in Caucasian and non-Caucasian populations. Two horizontal sinusoidal gratings differing in spatial frequency, i.e., 1 and 4 cycles per degree (cpd), were presented in an "odd-ball" paradigm to 17 patients with PD and 17 age-matched control subjects. While the 1 cpd stimulus, is not expected to reveal retinal dopaminergic deficency, but only visuocognitive deficits, the 4cpd may give direct information of both "retinal" and "cognitive" visual deficits. We measured the latencies and amplitudes of N70, P100 and P300 components, and derived the "normalized" measures of P300-N70 latency difference (Central Processing Time-CPT70), the P300-P100 latency difference (CPT100) and the P300 amplitude responses normalized to either N70 and P100 amplitude (Amplitude Ratios AR70 and AR100). Our results do show that cognitive electrophysiological deficits in younger PD patients exist in non-Caucasians, perhaps to an even greater degree than in Caucasians, and confirm that absolute and normalized ERP amplitude and latency abnormalities are a distinguishing feature of younger PD patients from controls. In particular P300 measures are abnormal for 1 cpd pattern. A negative correlation exists between P300 amplitude and the motor score. By comparing the results for 1 and 4cpd stimuli it can be concluded that "primary" and "cognitive" visual abnormalities are independently affected in PD, implying that visuo-cognitive abnormalities are not passively determined by retinal dopaminergic deficiency.

Central motor pathway evaluation using magnetic coil stimulation in hereditary motor and sensory neuropathy type I (HMSN type I, Charcot-Marie-Tooth disease).

Central Motor Conduction Time (CMCT) was investigated in 18 patients (5 m, 13 f; age range: 11-69 yrs) with clinical and electrophysiological features of HMSN type I, using Magnetic Coil (MC) stimulation. No one exhibited clinically pyramidal signs. Brain stimulation Motor Evoked Potentials (MEPs), recorded monolaterally from the left abductor digiti minimi (ADM) and tibialis anterior (TA) muscles, were evoked in all patients from upper extremities and absent in 11.1% from lower limbs. Total Motor Conduction Time (TMCT), as well as Peripheral Motor Conduction Time estimated by either magnetic nerve root stimulation (mag-PMCT) or F-wave latency values (F-PMCT), were markedly delayed in all patients. Central Motor Conduction Time was calculated by subtracting both the latency of mag-PMCT (mag-CMCT) and F-PMCT (F-CMCT) from that one obtained by cortical stimulation. F-CMCT was abnormal in 22.2% in upper extremities and in 27.8% patients from lower extremities, whereas mag-CMCT in 22.2% from ADM muscles and in 33.3% from TA muscles. Furthermore, CMCT to both methods was not possible to evaluate in 5.6% from upper and lower extremities and following magnetic root stimulation in 11.1% from lower limbs. These findings prove lower motor neuron involvement, in agreement with electroneurographic data, and suggest a possible central motor pathways impairment, even in patients without any clinical evidence, but they cannot explain which is the underlying pathophysiological mechanism, a true upper motor neuron involvement or an abnormal spinal motor neuron excitability.