Bruno Gregori

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 Parkinsons 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.

Sympathetic skin response and cardiovascular autonomic function tests in Parkinson's disease and multiple system atrophy with autonomic failure.

The relationship between sympathetic skin response (SSR) and cardiovascular autonomic function tests (CVTs) was investigated in 15 patients with idiopathic Parkinsons disease (PD), 15 patients with clinical evidence of multiple system atrophy (MSA) with autonomic failure, and in 15 healthy control subjects. SSR was elicited by electrical stimulation of the right and left median nerves and simultaneously recorded on the palms of both hands. CVTs included the following sympathetic and parasympathetic tests: orthostatism, head‐up tilt, cold pressor test, deep breathing, Valsalva maneuver, and hyperventilation. The SSR was normal in all patients with PD and control subjects but was abnormal or absent in all patients with MSA. For patients with MSA, SSR latency was significantly longer and amplitude was significantly smaller than that of patients with PD and control subjects. For patients with PD, SSR did not differ from that of control subjects. In these patients, SSR latency was significantly longer and SSR amplitude was smaller when the side with more marked motor symptoms was stimulated, both ipsilaterally and contralaterally to the side of stimulation. A statistically significant difference in SSR latencies and amplitudes was found between patients with PD and control subjects only when motor asymmetries were considered. CVTs showed severe sympathetic and parasympathetic hypofunction in patients with MSA, but not in patients with PD or control subjects. No correlation was found between SSR and CVTs that assess sympathetic function in patients and control subjects. SSR is indicated as an additional test for the evaluation of sympathetic degeneration in patients with MSA.

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.

Luminance and chromatic visual evoked potentials in type I and type II diabetes: relationships with peripheral neuropathy

The objective of the study was to investigate the subclinical visual deficit in type I and II diabetes, and its relationship with peripheral neuropathy. Thirty-two healthy volunteers, 20 patients with type I diabetes and 30 patients with type II diabetes were studied in a clinical neurophysiology setting. Luminance (VEPs) and chromatic visual evoked potentials (CVEPs) were recorded, with white-black, grey-black, red-green and blue-yellow sinusoidal gratings. The peak latencies of the VEP positive wave and CVEP negative wave were recorded. Ten patients with type I and 8 with type II diabetes had peripheral neuropathy. VEPs were slower in patients with type II diabetes and CVEPs were slower in patients with type I and type II diabetes than in controls. Blue-yellow CVEPs were slower in type II than in type I diabetes. VEPs and red-green CVEPs were slower in patients with diabetes with neuropathy than in those without. In conclusion, we found that visual system impairment differs in diabetes with and without peripheral neuropathy.

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<males) (P<0.001). No difference was found in the P100 latency in the subgroup of the two sexes with a comparable range of head size. CONCLUSIONS These findings suggest that VEP latency is relatively constant in a sample of healthy subjects. The slight sex difference in P100 latencies observed in a normal sample is mainly related to the slightly smaller average head size in females than in males. SIGNIFICANCE Head size, not sex, should be considered for VEP latency normative studies.

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.

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.

Chromatic modulation of luminance visual evoked potential latencies in healthy subjects and patients with mild vision disorders

OBJECTIVE To study whether and how color modulates luminance visual evoked potentials (VEPs). METHODS We studied pattern-reversal luminance VEPs to red/black and blue/black checkerboards with identical luminance contrast values (mixed luminance and chromatic components) (isocontrast color VEP, in brief, IVEPs) in 25 healthy subjects and two groups of patients with mild vision disorders (23 with glaucoma and 25 with optic neuritis). We then compared these with the standard color VEPs to pure chromatic contrast red/green and blue/yellow gratings (CVEPs). RESULTS In healthy subjects, VEPs to red/black checkerboards and red/green gratings were slower than those obtained with blue/black checkerboards and blue/yellow gratings. Both procedures (IVEPs and CVEPs) differentiated patients with vision disorders from healthy subjects and distinguished between the two different vision disorders. Red/black checkerboards and red-green gratings elicited slower VEPs in patients with optic neuritis and blue/black checkerboards and blue/yellow gratings elicited slower VEPs in patients with glaucoma. IVEPs appeared more stable and ample than CVEPs. The contrast indices normalized CVEP and IVEP latencies in the same subject and showed a positive correlation between CVEP and IVEP latencies in healthy subjects and in patients with optic neuritis, but not in patients with glaucoma. CONCLUSIONS Our study confirms the usefulness of CVEPs in detecting and differentiating mild vision disorders. IVEPs to colored pattern-reversal luminance checkerboards are equally effective in distinguishing between various vision disorders possibly because colors can modulate VEP latencies to luminance contrast stimuli. SIGNIFICANCE IVEPs can be useful in differentiating the various vision disorders and are easier than CVEPs to test in a routine clinical setting.