Francesco Fattapposta

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.

Abnormalities of Cognitive Functions in IDDM Revealed by P300 Event-Related Potential Analysis: Comparison With Short-Latency Evoked Potentials and Psychometric Tests

The possible influence of diabetes on the higher mnestic and cognitive functions has been investigated. The P300 wave latency, an endogenous electrophysiological event, was explored and compared with the multimodal short-latency evoked potential (EP) recordings (visual [VEP], brainstem auditory [BAEP], and median and tibial nerve somatosensory EPs [mSEP and tSEP, respectively]) and psychometric test measures in 16 insulin-dependent diabetic (IDDM) patients, in 16 age- and (IDDM) sex-matched nondiabetic subjects, and in a large normal reference population. The age of subjects, the duration of IDDM, and the metabolic control of patients were taken into account. P300 values were significantly increased in IDDM versus matched control subjects (P < 0.001), and 3 patients showed values above the reference value range. Abnormal VEP recordings were present in 1 of 16 patients, BAEP in 3 of 16, mSEP in 7 of 16, and tSEP in 6 of 16. Digit-span backward test results were significantly (P < 0.02) modified in the diabetic cohort. There was no tendency for anomalies of P300, short-latency EPs, and psychometric test values to be contemporarily present, except in 1 patient. Electrophysiological or psychometric abnormalities were not clearly correlated with the duration of IDDM or the degree of short-term metabolic control. These findings give evidence that 1) higher cognitive functions may be affected in diabetes as documented by P300 analysis and short-term memory tests, 2) endogenous electrophysiological analysis highlights neuropsychological changes not detectable by psychometric tests, 3) an alteration of evoked potentials was present in half of the IDDM subjects studied, and 4) anomalies of the CNS are patchily distributed in diabetes.

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.

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.

Early visual function impairment in CADASIL.

The authors carried out genetic analyses and visual electrophysiologic evaluations in six asymptomatic sons and daughters of patients with symptomatic cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Three subjects showed Notch3 Cys146Tyr missense mutation and a dysfunction of the outer, middle, and innermost retinal layers, with normal neural conduction in postretinal visual pathways, whereas in the remaining subjects without genetic mutations, no electrophysiologic abnormalities were found. An early vascular retinal impairment in CADASIL may precede the onset of clinical manifestations.

L-Dopa decreases cutaneous nociceptive inhibition of motor activity in Parkinson's disease.

Objectives– To estimate changes in motor inhibitory mechanisms at the spinal level in Parkinsons disease (PD) patients by measuring cutaneous silent responses to nociceptive stimuli in the course of L‐Dopa therapy. Material and methods– Fourteen patients with idiopathic PD (Group 1) and 13 patients with other forms of parkinsonism (Group 2) participated in the study. The cutaneous silent period (CSP) from the hand and clinical scores (UPDRS, part III) were measured “off” therapy (T0), after a single dose of L‐Dopa (T1) and 3 months after the beginning of L‐Dopa daily therapy (T2). Results– At T0 the duration of the CSP was significantly prolonged in Group 1 and Group 2. At T1 and T2 the mean duration of the CSP significantly decreased in Group 1 (P < 0.05) and a significant correlation was found between the shortening of the CSP and the improvement of rigidity and bradikynesia in the upper limb. Conclusions– Our findings show that L‐Dopa decreases the cutaneous nociceptive inhibition of motor activity in PD patients. CSP may be useful to assess L‐Dopa responsiveness during the clinical course of PD.

Gilles de la Tourette syndrome and voluntary movement: A functional MRI study

Tourette syndrome (TS) is hypothesised to be caused by an abnormal organization of movement control. The aim of this study was to use functional magnetic resonance imaging to study motor cortex activation in a TS patient. Usual and unusual self-paced voluntary movements were performed. The TS patient displayed supplementary motor area (SMA) activation during both tasks. This activation reflects a continuous use of the SMA to perform the voluntary motor movements required in both tasks. Moreover, the absence of tics during the execution of these voluntary motor tasks suggests that tic activity may be suppressed by additional mental effort.

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.

Reversible diffusion MRI abnormalities and transient mutism after liver transplantation

Transient mutism was observed in a liver transplant patient under immunosuppressant therapy with cyclosporine A and antifungal prophylaxis with amphotericin B. Fluid-attenuated inversion recovery and diffusion-weighted images revealed reversible bilateral symmetric hyperintensity located in the frontal motor cortex and corticospinal tracts. These MRI abnormalities may be caused by acute edema, possibly a combination of cytotoxic and vasogenic edema, which resolved with a prompt change in therapy.

Dopaminergic pharmacological manipulations in normal humans confirm the specificity of the visual (PERG-VEP) and cognitive (P300) electrophysiological alterations in Parkinson's disease.

Retinal and occipital visual evoked potentials and event-related potentials (P300) have been recorded in normal human subjects before and after the administration of the dopaminergic receptor antagonist, haloperidol, and/or the dopaminergic precursor L-DOPA. The data show that either retinal or occipital visual potentials and P300 are delayed by haloperidol. These findings are consistent with the hypothesis that haloperidol in healthy subjects mimicks the electrophysiological abnormalities observed in Parkinsons disease. On the other hand, L-DOPA does not generally modify these latencies in normals, while it is known to decrease the same parameters in parkinsonian patients. This is in accord with the involvement of a specific mechanism in the recovery observed in parkinsonian patients after L-DOPA therapy. Our data confirm that the alterations of visual and cognitive potentials observed in Parkinsons disease are closely related to the impairment of dopaminergic transmission.