Caterina Pauletti

Donepezil in the treatment of hallucinations and delusions in Parkinson's disease.

As cholinergic mechanisms may be at least partially responsible for hallucinations and delusions in Parkinson’s disease (PD), we conducted an open study in 8 PD patients to assess the efficacy and tolerability of the cholinesterase inhibitor donepezil, 5 mg at bedtime for two months, in the treatment of these complications. Hallucinations and delusions improved significantly in all patients. Donezepil was overall well tolerated, but a deterioration in motor disability was noted in 2 out of 8 patients.

Excessive daytime sleepiness in de novo and treated Parkinson's disease

Excessive daytime sleepiness (EDS) in Parkinsons disease (PD) is due to either treatment‐related factors or the disease itself. The study of this disturbing phenomenon in de novo parkinsonian patients may contribute to a better understanding of its pathophysiology. We conducted a case control study in which we compared 25 PD patients who had never been treated before with dopaminergic drugs (de novo PD), 50 PD patients being treated with dopaminergic drugs (treated PD), and 25 healthy control subjects, all of whom were matched for age and gender. EDS was measured by means of the Epworth Sleepiness Scale (ESS) and quality of sleep by means of the Pittsburgh Sleep Quality Index (PSQI). ESS and PSQI scores were not statistically different between de novo PD patients and controls, whereas they were significantly higher in treated PD. Differences in ESS score variability were best explained by the treatment effect, whereas there was no clear correlation between PSQI and any of the clinical variables considered.

Excessive daytime somnolence in Parkinson's disease. Follow-up after 1 year of treatment.

Abstract.Excessive daytime somnolence (EDS) and quality of sleep were studied in 25 parkinsonian patients at baseline, when they had not yet received any antiparkinsonian medication, and after 1 year of treatment with dopaminergic drugs. EDS was measured by the Epworth Sleepiness Scale (ESS) and sleep quality by the Pittsburgh Sleep Quality Index (PSQI). At baseline, the ESS score was not different from that of agematched healthy controls. The mean ESS score increased significantly after 1 year of follow-up, being more than 10 in 12 patients. The mean PSQI also increased significantly after 1 year of treatment, but there were no differences in the number of “bad sleepers” at baseline and at follow-up. In conclusion, EDS seems to emerge during the course of the illness, at least in a proportion of PD patients, and could represent another clinical correlate of the interaction between the ongoing neurodegenerative process and the side effects of drugs.

Prefrontocerebellar transcranial direct current stimulation increases amplitude and decreases latency of P3b component in patients with euthymic bipolar disorder

Introduction Neurocognitive impairments have been observed in patients with bipolar disorder (BD) even during the euthymic phase of the disease, potentially representing trait-associated rather than state-associated characteristics of the disorder. In the present study, we used transcranial direct current stimulation (tDCS) applied to cerebellar and prefrontal cortices to improve the neurophysiological performances of patients with euthymic BD. Methods Twenty-five outpatients with BD underwent open-label prefrontocerebellar tDCS for 3 consecutive weeks. Neurophysiological performances were assessed through the examination of the P3b and P3a subcomponents of P300 event-related potential at baseline and after stimulation. Results Compared to baseline, P3b component after tDCS showed significantly higher amplitude and shorter latency (latency: Fz P=0.02, Cz P=0.03, and Pz P=0.04; amplitude: Fz P=0.24, Cz P=0.02, and Pz P=0.35). Conclusion In our sample of patients with euthymic BD, concomitant prefrontoexcitatory and cerebellar-inhibitory modulations led to improved brain information processing stream. This improvement may at least partially result from neuroplastic modulation of prefrontocerebellar circuitry activity.

An atypical case of neuro-Whipple: Clinical presentation, magnetic resonance spectroscopy and follow-up

We report a case of a 53-year-old man with a 2-year history of progressive gait and balance disturbance, supranuclear ophthalmoparesis, mild dysarthria and dysmetria. EMG revealed a lower limb axonal sensory-motor neuropathy, while MR imaging demonstrated a small focal lesion in the right frontal lobe, mild diffuse hyperintensity of the periventricular white matter and diffuse brain atrophy. Magnetic resonance spectroscopy revealed a mild decrease in N-acetyl-aspartate peak and an increase in the choline peak in the small right frontal lesion and within 6 voxels of interest in normal appearing cerebral tissue. According to the clinical picture the diagnosis of WD was made by the positivity of PCR for T. whipplei DNA on CSF. After treatment the patient showed a mild clinical improvement although MR images and laboratory test remained unchanged. The MRS findings suggest that the pathological process of the disease diffusely involves the brain. Despite the absence of gastrointestinal involvement WD should be suspected in all complex and atypical neurological pictures, even in presence of peripheral involvement, in order to be able to start treatment promptly.

The Role of the Right Dorsolateral Prefrontal Cortex in Phasic Alertness: Evidence from a Contingent Negative Variation and Repetitive Transcranial Magnetic Stimulation Study

Phasic alertness represents the ability to increase response readiness to a target following an external warning stimulus. Specific networks in the frontal and parietal regions appear to be involved in the alert state. In this study, we examined the role of the right dorsolateral prefrontal cortex (DLPFC) during the attentional processing of a stimulus using a cued double-choice reaction time task. The evaluation of these processes was conducted by means of Event-Related Potentials (ERPs), in particular by using the Contingent Negative Variation (CNV), and repetitive 1-Hz Transcranial Magnetic Stimulation (rTMS). Transient virtual inhibition of the right DLPFC induced by real 1-Hz rTMS stimulation led to a significant decrease in total CNV and W1-CNV areas if compared with the basal and post-sham rTMS conditions. Reaction times (RTs) did not decrease after inhibitory rTMS, but they did improve after sham stimulation. These results suggest that the right DLPFC plays a crucial role in the genesis and maintenance of the alerting state and learning processes.

Attentional processing in bulbar- and spinal-onset amyotrophic lateral sclerosis: Insights from event-related potentials

Abstract Our objective was to evaluate attentional processing with respect to the clinical-onset subtype in amyotrophic lateral sclerosis (ALS) using event-related potentials (ERPs). Thirty-three non-demented ALS patients (22 spinal onset, 11 bulbar onset) and 32 age- and gender-matched controls underwent a psychophysiological evaluation. Mismatch Negativity (MMN), P300 components and Contingent Negative Variation (CNV) were obtained. Latencies and amplitudes of the MMN, P3a and P3b waves and CNV amplitude were then evaluated. Clinical parameters were correlated with ERP data. No differences emerged between ALS patients and controls with regard to the MMN and P3b components. N1-P3a inter-peak latency (Fz, p = 0.003; Cz, p = 0.001; Pz, p = 0.002) was longer in ALS-b than in ALS-s. Total CNV area (Cz, p = 0.01) and W1-CNV area were significantly reduced (Cz, p = 0.05; Pz, p = 0.03) in ALS-b with respect to the one of the controls, while no differences were found between ALS-s patients and controls. In conclusion, automatic pre-attentive processing of stimuli seems to be preserved in ALS. However, a significant delay in the time-course of selective attentive processing and a difficulty in initiating and sustaining attention may be present in ALS-b, which points to a possible dysfunction in the frontal neural network that responds to novelty and to abnormal integration of associative functions. This attentional impairment should be taken in account while developing alternative communicative strategies in ALS patients.

Unusual posterior reversible encephalopathy syndrome in a case of influenza A/H1N1 infection

Central nervous system involvement is an uncommon though potentially a severe complication during influenza infection; the pathogenic mechanisms of the neurological syndromes described in humans are largely unknown. We describe a case of a 51-year-old man who presented with fever and behavioral changes but no focal neurological deficits. The next day, the condition rapidly evolved into a severe neurological syndrome with recurrent focal motor seizures with secondary generalization. At the brain MRI, FLAIR disclosed a slight area of increased signal in the left mesial frontal cortex extending to the frontopolar area and insula. At DWI, a mild hyperintensity was evident in the mesial-frontopolar cortex, with normal ADC values. MR perfusion was indicative of severe hypoperfusion. Fungal, bacterial and viral cultures in CSF, blood and urine were negative. The nasopharyngeal swab PCR was positive for the H1N1-influenza A virus. The patient was thus treated and by day five the neurological examination results had returned to normal. A follow-up MRI, performed two weeks later, only revealed a residual slight hyperintensity in the left medial frontal cortex. The onset of a rapidly evolving encephalopathy syndrome, its close association with a MRI brain pattern of acute vasogenic edema and favorable outcome support a diagnosis of PRES during influenza A infection. However, the topographic characteristics of the cerebral lesion seem to define a PRES with an atypical pattern.

Effects of cerebellar transcranial direct current stimulation on attentional processing of the stimulus: Evidence from an event-related potentials study

Attentional processing consists of a set of processes that manage the flow of information through the nervous system and appropriately allocate attentional resources to relevant stimuli. Specific networks in the frontal and parietal regions appear to be involved in attention. The cerebellum has been identified as a subcortical structure that interacts with cortical brain areas, thereby controlling attentional processes. The aim of this study was to investigate the role of the cerebellum in attentional processing of the stimulus using a P300 Novelty task. We studied the effects of transcranial Direct Current Stimulation (tDCS) delivered over the left cerebellar hemisphere in cathodal, anodal and sham sessions on the P300 components in healthy subjects. Only cathodal cerebellar tDCS significantly reduced the amplitude of the N1, N2 and P3 components for both the target and novel stimuli. Moreover, N1 latency for all the stimuli was shorter after the cathodal tDCS session than after the sham or anodal sessions. These results point to a role of the cerebellum in attentional processing of the stimulus. The cerebellum may act indirectly by regulating and managing the activation and inhibition levels of the cortical areas involved in attentional networks.

Prefronto-cerebellar tDCS enhances neurocognition in euthymic bipolar patients. Findings from a placebo-controlled neuropsychological and psychophysiological investigation

OBJECTIVES The present double blind placebo-controlled study aimed at investigating the efficacy of 3-weeks prefronto-cerebellar transcranial direct current stimulation (tDCS) on neurocognitive functioning in euthymic BD patients. METHODS Forty-two outpatients with BD were randomly assigned to receive either active (n=21) or sham (n=21) prefronto-cerebellar tDCS for 3 consecutive weeks. Neurocognitive abilities were assessed with both neuropsychological testing and psychophysiological evaluation with a P300 novelty task. RESULTS Our results showed that (i) Trail Making Test-B, a measure of executive functioning, decreased significantly in the active but not in the sham group, (ii) Rey Complex Figure Test Delay Recall, a measure of visuospatial memory, increased significantly in both groups with a greater increase in the active compared to the sham group, and (iii) P3b latency, a measure of brain information processing stream, decreased significantly in the active but not in the sham group. No significant changes were observed in the other explored neuropsychological and psychophysiological measures. CONCLUSIONS The study suggests that concomitant prefrontal-excitatory and cerebellar-inhibitory tDCS in euthymic BD patients may lead to better neurocognitive performance, quantified through neuropsychological and psychophysiological measures.