G. Amabile

Indobufen Versus Warfarin in the Secondary Prevention of Major Vascular Events in Nonrheumatic Atrial Fibrillation

BACKGROUND AND PURPOSE The results of a large prospective randomized trial have shown the efficacy of oral anticoagulation in the secondary prevention of major vascular events in patients with nonrheumatic atrial fibrillation (NRAF); less well established is the role of antiplatelet agents. The present study compared the effects of indobufen, a reversible inhibitor of platelet cyclooxygenase, with those of warfarin in this setting. METHODS A total of 916 patients with NRAF and a recent (< or = 15 days) cerebral ischemic episode were admitted to this multicenter, randomized study, during which they were treated with either indobufen (100 or 200 mg BID) or warfarin (to obtain an international normalized ratio of 2.0 to 3.5) for 12 months. The two groups (462 on indobufen and 454 on warfarin) were well balanced in terms of their main baseline characteristics. The primary outcome of the study was the combined incidence of nonfatal stroke (including intracerebral bleeding), pulmonary or systemic embolism, nonfatal myocardial infarction, and vascular death. RESULTS At the end of follow-up, the incidence of primary outcome events was 10.6% in the indobufen group (95% confidence interval, 7.7% to 13.5%) and 9.0% in the warfarin group (95% confidence interval, 6.3% to 11.8%), with no statistically significant difference between treatments. The frequency of noncerebral major bleeding complications was low: only four cases (0.9%) of gastrointestinal bleeding were observed, all of them in the warfarin group. CONCLUSIONS We conclude that, within the limitations of its design, this study may help the medical community in devising appropriate antithrombotic strategies for NRAF patients for whom oral anticoagulants are contraindicated or do not represent a feasible approach to treatment.

Effects of diffuse noxious inhibitory controls on temporal summation of the RIII reflex in humans

&NA; The aim of this study was to investigate the effects of diffuse noxious inhibitory controls (DNICs) on the temporal summation of the nociceptive flexion reflex (RIII reflex) in humans. Recordings were obtained from 36 healthy adults (16 M, 20 F), and the area and temporal summation threshold (TST) of the RIII reflex were measured. The subjective intensity of the painful sensation was rated on an 11‐point visual analogue scale (VAS). Neurophysiological and VAS measurements were recorded after activation of DNICs by means of the cold pressor test (CPT), which involved immersing the hand in cold water (2–4 °C). A slight significant lower TST was found in the females versus the males. In all the subjects, the CPT induced a significant TST increase and RIII area reduction compared with the control session. The VAS results paralleled those of the RIII reflex area and TST. During the CPT, a significant difference in the percentage TST increase emerged between females and males, being lower in the former. Similarly, we found a significantly lower percentage reduction of the RIII area in women than in men during the CPT. To summarize, activation of DNICs through the CPT significantly increased the TST of the RIII reflex in healthy subjects. This inhibitory effect was gender‐specific. Whereas other findings are based on psychophysical evaluations, the results of this experimental study provide an objective neurophysiological demonstration that DNICs attenuate temporal summation in humans and confirm the presence of significant differences in pain modulation mechanisms between men and women.

Olfactory screening test in mild cognitive impairment

AbstractMild cognitive impairment (MCI) is a transient status between physiologic ageing and dementia. Each year more than 12% of subjects with MCI develop Alzheimer’s disease. This study evaluated the presence of an olfactory deficit in amnesic MCI (aMCI) patients. Twenty–nine patients diagnosed with aMCI and a homogeneous control group of 29 subjects were enrolled in the study. Olfactory function was assessed by the Sniffin’ Sticks Screening Test (SSST) and the Mini Mental State Examination, the Clinical Dementia Rating, the Geriatric Depression Scale and the Mental Deterioration Battery were used to evaluate the neurocognitive status. aMCI patients showed a significant impairment of their olfactory identification compared to controls (SSST score: 8.3±2.1 vs. 10.8±0.9; p<0.001). These results suggest that olfactory tests should be part of the diagnostic armamentarium of pre–clinical dementia. A long–term follow up might confirm the olfactory identification function as an early and reliable marker in the diagnosis of pre–clinical dementia.

Parkinson disease: Electrophysiological (CNV) analysis related to pharmacological treatment

The contingent negative variation (CNV) was studied in a group of patients with Parkinsons disease. Testing was carried out 3 times: after a pharmacological wash-out period and at 15 and 30 days after the start of treatment with L-DOPA and bromocriptine. Peak and area CNV increased significantly after each treatment. The post-imperative negative variation (PINV) was observed in 6 out of 10 patients. The correlation found between electrophysiological functioning (CNV) measures and pharmacological treatment supports the view that dopaminergic brain activity mediates the generation of the slow negative event-related brain potentials.

Modern psychophysical tests to assess olfactory function.

AbstractThe sense of smell significantly contributes to quality of life. In recent years much progress has been made in understanding the biochemistry, physiology and pathology of the human olfactory system. Olfactory disorders may arise not only from upper airway phlogosis but also from neurodegenerative disease. Hyposmia may precede motor signs in Parkinson’s disease and cognitive deficit in Alzheimer’s disease. These findings suggest the complementary role of olfactory tests in the diagnosis and management of neurodegenerative diseases. In this report we present a review of modern olfactory tests and their clinical applications. Although rarely employed in routine clinical practice, the olfactory test evaluates the ability of odour identification and is a useful diagnostic tool for olfaction evaluation. Olfactory screening tests are also available. In this work we strongly recommend the importance of an ENT evaluation before the test administration and dissuade from a self–administration of an olfactory test.

Muscular cramps: Proposals for a new classification

Muscle cramps are involuntary, painful, sudden contractions of the skeletal muscles. They are present in normal subjects under certain conditions (during a strong voluntary contraction, sleep, sports, pregnancy) and in several pathologies such as myopathies, neuropathies, motoneuron diseases, metabolic disorders, hydroelectrolyte imbalances or endocrine pathologies. There has been considerable uncertainty in the literature regarding the classification and nomenclature of muscle cramps, both because the term “cramp” is used to indicate a variety of clinical features of muscles, leading to its use as an imprecise “umbrella” term that includes stiffness, contractures and local pain, and because the spectrum of the diseases in which it appears is wide. The purpose of the present study is to propose a simple classification to provide a framework to better recognize the full spectrum of phenomenology of muscle cramps.

Trigemino-cervical-spinal reflexes in humans

INTRODUCTION Electrical stimulation of the supraorbital nerve (SON) induces late reflex responses in the neck muscles; these responses are hypothesised to be polysynaptic reflexes participating in a defensive withdrawal retraction of the head from facial nociceptive stimuli. Such responses may extend to the proximal muscle of the arms. OBJECTIVE (1) to investigate reflexes in the upper limb muscles (trigemino-spinal responses, TSR) and their relationship with trigemino-cervical responses (TCR); and (2) to identify the nociceptive component of such reflexes and their functional significance. METHODS Reflex responses were registered from the semispinalis capitis and biceps brachii muscles after electrical stimulation of the SON in 12 healthy subjects. The sensory (ST), painful (PT) and reflex thresholds, the latency and area of the responses, the effect of heterotopic painful stimulation (HTP), the recovery cycle as well as the effect of the expected and unexpected stimuli were measured. RESULTS Stable reproducible TCR and TSR responses were identified at 2.5+/-0.4 x ST, which corresponded exactly to the PT in all the subjects. The TCR and TSR areas were markedly reduced after HTP. The recovery cycle of the TSR area was faster than that of the TCR. Repeated rhythmic stimulation failed to induce progressive reflex suppression. CONCLUSIONS These results confirm the nociceptive nature of the TCR and indicate that the biceps brachii response (TSR) has the same nocifensive significance as the posterior neck muscle responses. TCR and TSR are mediated different polysynaptic pathways The presence of trigemino-cervical-spinal responses in our study clearly indicates that there is a reflex interaction between nociceptive trigeminal afferents and both upper and lower cervical spinal cord motoneurons.

A simple method for estimating conduction velocity of the spinothalamic tract in healthy humans

OBJECTIVES The object of this study was to establish a method for estimating the conduction velocity (CV) of the spinothalamic tract (STT) in relation to clinical application. METHODS The CV of the STT was estimated by an indirect method based on that reported by Kakigi and Shibasaki in 1991 (Kakigi R, Shibasaki H. Electroenceph clin Neurophysiol 80 (1991) 39). Laser-evoked potentials (LEP) were measured in 8 subjects following hand (LEPH) and foot (LEPF) laser stimulation. The conduction times recorded at the scalp (P340, P400 and N150 potentials) were considered as the summation of peripheral and central components. The peripheral conduction times were calculated by measuring the latency of the electrical cutaneous silent period (from the same stimulus site of LEPs), corrected for F- and M-wave latency values. RESULTS The CV of the STT ranged between 8.3 and 11.01 m/s and its mean value was found to be approximately 9.87+/-1.24 m/s. The CV of the STT obtained by the N150 latencies overlapped that obtained by the P340/P400 latencies. CONCLUSIONS Our data suggest that our method appears appropriate and useful for practical clinical purposes, furnishing an additional tool for investigating the physiological function of small-fiber pathways.

Effect of painful heterotopic stimulation on the cutaneous silent period in the upper limbs

OBJECTIVE To evaluate the effect of heterotopic painful stimulation (HPS) on the cutaneous silent period (CSP) and the withdrawal flexor reflex (WFR) in the upper limbs, in an attempt to better identify the nociceptive component of the CSP and its functional relationship with the flexor reflex. METHODS The CSP at different stimulus intensities, the WFR and the H/M ratio were studied in 12 healthy adults. Neurophysiological measurements were recorded in the following 4 conditions: (1) control session; (2) non-painful session (dipping hand in water at 25 degrees C); (3) painful (cold pressor test, CPT); and (4) after-effect (3-8 min after taking hand out of water at 5-6 degrees C). RESULTS During the CPT, the duration of the high-threshold CSP was approximately 23% shorter than the baseline value, the high-threshold CSP latency was approximately 10% longer than the baseline value, and the mean RIII reflex area was approximately 40% smaller than the baseline reflex area (all P<0.05). A significant correlation was found between the percentage decrease in the CSP duration and the WFR area (r=0.61, P<0.05). CONCLUSIONS Our findings indicate that the HPS specifically inhibits both the high-threshold CSP and the WFR, thereby providing further evidence that these cutaneous reflexes are functionally and anatomically related, and that they represent different aspects of a complex nocifensive response.

Preprogramming and control activity of bimanual self-paced motor task in Parkinson's disease

OBJECTIVE The authors investigated programming (Bereitschaftspotential or BP) and control activity (Skilled Performance Positivity or SPP) of a bimanual, sequential, skilled motor act in off-therapy Parkinsons disease (PD) patients. METHODS We recorded Movement Related Potentials (MRPs) in 12, non-demented, off-therapy parkinsonian patients and in 17 control subjects who were performing a skilled, time-locked motor act, which was not routine in their everyday life but had to be learned: the Skilled Performance Task (SPT). BP, SPP and correct performances were evaluated in grand average waveforms and in sequential blocks. RESULTS The analysis of correct performances showed that accuracy in PD patients was significantly lower than in the control group and this accuracy did not improve throughout the blocks. A significantly low level of performances was associated with an increased BP amplitude (P<0.05) and decreased SPP amplitude (P<0.05) in PD patients. CONCLUSION Our findings suggest that skill motor learning is impaired in non-demented unmedicated PD patients. We discuss the view that PD patients may allocate more attentional resources, as suggested by the increased BP amplitude, the decreased SPP amplitude and the low correct performances, in order to perform a new skilled motor act.