Neri Accornero

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. (HEPATOLOGY 2005;42:1158–1165.)

Clinical multisegmental posturography: Age-related changes in stance control

Unlike conventional platform posturography, which analyses the sway in the projection of the body baricentre on a supporting plane, multisegmental posturography provides information about body segmental movements during stance, including those that keep the baricentre still. This paper presents a new technical approach to multisegmental posturography using Virtual Reality electromagnetic tracking devices. This device was used to study age-related differences in normal subjects in the control of upright posture. Body sway was studied by recording the oscillations of two trackers placed on the head and the hip during the Romberg test. The tracking device allowed us to detect age-related differences in postural stance strategies. Although the amplitude and velocity of the oscillations measured at the head did not differ in the two groups, the flexibility of the ankle-hip head axis differed significantly: elderly subjects exhibited a more rigid stance. Closing the eyes increased rigidity in both age groups and this change appear more pronounced in the young.

Fast complex arm movements in Parkinson's disease.

Fast arm movements involving the shoulder and elbow joints have been analysed in normal controls and in patients with Parkinsons disease. The subjects were requested to draw on a graphic tablet triangles and squares of different size and shape. The patients produced a larger number of EMG burst compared with controls. The movements were accurate, and each segment of the geometric figures was performed with a roughly straight trajectory, but the time necessary to trace the geometric figures and the pauses at the vertices were prolonged. We conclude that in Parkinsons disease the disability in generating two joint ballistic movements depends on a difficulty in running motor programmes for complex trajectories.

Stimulation of motor tracts in motor neuron disease.

The muscle responses evoked by cortical and cervical stimulation in 11 patients with motor neuron disease were studied. The muscle potential in the abductor pollicis brevis, evoked by median nerve stimulation and the somatosensory potential evoked by wrist stimulation were also studied. In eight of 11 patients there was absence or increased central delay of the responses evoked by cortical stimulation. In four patients muscle responses on cervical stimulation and muscle action potentials on median nerve stimulation were also altered, indicating peripheral abnormalities. Somatosensory responses evoked by wrist stimulation were normal. Electrophysiological techniques are helpful in estimating the site of motor involvement in motor neuron disease.

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.

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.

Two joints ballistic arm movements

Fast planar arm movements involving two joints have been analyzed in humans. The EMG activity associated with the drawing of straight lines or geometric figures was characterized by sequences of bursts in the agonist and antagonist muscles of constant duration and different amplitude. The shape of each trajectory is defined by a particular sequence of burst activity in the four muscles studied. A pattern of one burst in the agonist and one in the antagonist is the basic building block for different kinds of ballistic trajectories. The time of execution increased linearly with the number of sides of the geometric figures by steps of about 210 ms and did not increase linearly with their size.

The orbicularis oculi response after hemispheral damage.

The corneal and blink reflexes were evaluated in 20 normal subjects and in 30 patients with motor deficits secondary to unilateral hemispheral lesions of vascular origin. In the normal population there were no differences between subjects below and subjects above 50 years of age. In the patients the reflex evoked by electrical stimulation of the cornea of the clinically affected side was depressed in 24 out of 30 cases. The depression mainly affected the afferent branch of the circuit, which triggers both homolateral and contralateral orbicularis oculi discharge (afferent abnormality). In three cases the depression was exerted concomitantly on the efferent branch (afferent and efferent abnormality) and only in one case was it limited to the efferent branch (efferent abnormality). The late R2 component of the blink reflex was depressed in 15 out of 30 patients. The early R1 component was slightly facilitated on the affected side. The changes of the corneal reflex and of the R2 component of blink reflex were similar, but the blink reflex had a greater safety factor. The patients with an abnormal corneal reflex had more extensive damage than had the patients with normal corneal response, as shown by computer tomography, but the site of the lesion was comparable in the two groups. Conduction through the brain stem circuits mediating the orbicularis oculi response is normally under pyramidal facilitatory influences while facial motoneurons are subjected to pyramidal inhibition. After pyramidal damage the transmission of impulses in the brain stem was slowed down, ultimately to a degree that abolished the reflex. Removal of pyramidal inhibition on facial motoneurons is probably the basis of the slight facilitation of the R1 component of the blink reflex.

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.

Stimulation of motor tracts in multiple sclerosis.

Percutaneous electrical stimulation of the motor cortex was used to evaluate corticospinal conduction to upper-limb motoneurons in 29 patients with multiple sclerosis. Central motor conduction abnormalities were correlated with clinical signs and somatosensory evoked potentials. Muscle responses to cortical stimulation were altered in 20 patients. The most common abnormality was increased central motor conduction time; in two cases the responses to cortical stimulation were absent. Abnormalities were also present in patients with no clinical evidence of corticomotoneuron deficit. Alterations of muscle responses and of somatosensory evoked potentials were usually correlated, but may appear independently. Both testing methods are useful in the study of patients with multiple sclerosis.