Visual hallucinations in PD and Lewy body dementias: old and new hypotheses.

Visual Hallucinations (VH) are a common non-motor symptom of Parkinson's Disease (PD) and the Lewy body dementias (LBD) of Parkinson's disease with dementia (PDD) and Dementia with Lewy Bodies (DLB). The origin of VH in PD and LBD is debated: earlier studies considered a number of different possible mechanisms underlying VH including visual disorders, Rapid Eye Movement (REM) Sleep Intrusions, dysfunctions of top down or bottom up visual pathways, and neurotransmitter imbalance. More recently newer hypotheses introduce, among the possible mechanisms of VH, the role of attention networks (ventral and dorsal) and of the Default Mode Network (DMN) a network that is inhibited during attentional tasks and becomes active during rest and self referential imagery. Persistent DMN activity during active tasks with dysfunctional imbalance of dorsal and ventral attentional networks represents a new hypothesis on the mechanism of VH. We review the different methods used to classify VH and discuss reports supporting or challenging the different hypothetical mechanisms of VH.

Cefixime-induced nonconvulsive status epilepticus.

Nonconvulsive status epilepticus (NCSE) is an epileptic condition lasting >30 min, clinically manifested by an altered mental state and associated with continuous epileptiform activity on the electroencephalogram. NCSE is a common yet still under recognized condition and delay in diagnosis and treatment may be associated with increased mortality as well as cognitive/behavioral consequences. We described an epileptic female patient assuming carbamazepine (900 mg/day) and levetiracetam (3,000 mg/day), seizure free for more than 10 years, who developed NCSE during cefixime treatment, a third-generation cephalosporin compound that along with penicillins is classified within the b-lactam class of antibiotics. In our report we outline the importance and the difficulty to choose secure antibiotic treatment in epileptic patients, we discuss the possible mechanisms by which cephalosporins induce neurotoxicity and the need to stress family components questioning about new drugs assumed. Finally we highlight the value of the EEG recording to diagnose NCSE and treat it adequately and promptly.

Revisiting P300 cognitive studies for dementia diagnosis: Early dementia with Lewy bodies (DLB) and Alzheimer disease (AD).

AIMS OF THE STUDY: Earlier P300 studies were conducted when the prevalence of dementia with Lewy Bodies (DLB) was unknown. Our study aims to examine whether P300 abnormalities are present in DLB and to evidence possible differences between DLB and Alzheimer's disease (AD). A second aim of this study is to look for correlations between P300 recordings and EEG, as abnormal EEG variability has been described in DLB. PATIENTS AND METHODS: Auditory P300 responses were recorded by a classic oddball paradigm in 50 controls, in 36 DLB patients, and in 40 AD patients with MMSE>20. RESULTS: Reliable auditory P300 responses were obtained in 26 DLB (72%), 33 AD (82.5%), and 46 controls (92%). P300 was more delayed and had lower amplitude in DLB compared to AD groups. P300 topography was also different as the anterior-to-posterior scalp amplitude gradient was reversed in DLB. P300 latency correlated with neuropsychological test scores and with EEG variables. Gradient inversion and delayed P300 responses in frontal derivations evidenced differences between DLB and AD patients with a sensitivity of 70% and a specificity of 97%. CONCLUSIONS: P300 recordings are abnormal in DLB and can be useful to distinguish DLB from AD.

Protracted benefit from paradoxical kinesia in typical and atypical parkinsonisms.

Paradoxical kinesia (PK) is the sudden resolution of a previously stabilized akinesia in an advanced idiopathic Parkinson's disease (IPD) patient facing an immediate threat. We are reporting the effect of PK, as a consequence of a life threatening event (earthquake), in a group of 14 patients with parkinsonism and dementia in Hoehn/Yahr (H/Y) stage 3-5. All the patients presented an extraordinary motor response during the earthquake that has recently stricken the Italian city of L'Aquila. All of them were able to safely escape unaided and, in some cases, to assist their families, despite they suffered before from severe night time akinesia and gait difficulties with postural instability requiring assistance. In five patients, the improvement of motor disabilities, particularly of freezing, lasted for 2-5 months.

Persistent genital arousal disorder associated with functional hyperconnectivity of an epileptic focus.

Persistent Genital Arousal Disorder (PGAD) refers to the experience of persistent sensations of genital arousal that are felt to be unprovoked, intrusive and unrelieved by one or several orgasms. It is often mistaken for hypersexuality since PGAD often results in a high frequency of sexual behaviour. At present little is known with certainty about the etiology of this condition. We described a woman with typical PGAD symptoms and orgasmic seizures that we found to be related to a specific epileptic focus. We performed a EEG/MEG and fMRI spontaneous activity study during genital arousal symptoms and after the chronic administration of 300 mg/day of topiramate. From MEG data an epileptic focus was localized in the left posterior insular gyrus (LPIG). FMRI data evidenced that sexual excitation symptoms with PGAD could be correlated with an increased functional connectivity (FC) between different brain areas: LPIG (epileptic focus), left middle frontal gyrus, left inferior and superior temporal gyrus and left inferior parietal lobe. The reduction of the FC observed after antiepileptic therapy was more marked in the left than in the right hemisphere in agreement with the lateralization identified by MEG results. Treatment completely abolished PGAD symptoms and functional hyperconnectivity. The functional hyperconnectivity found in the neuronal network including the epileptic focus could suggest a possible central mechanism for PGAD.

Long half-life and prolonged-release dopamine receptor agonists: a review of ropinirole prolonged-release studies.

Our review summarizes the five main studies conducted to evaluate the efficacy and pharmacokinetics of ropinirole prolonged release (PR) in Parkinson's disease (PD). The PR formulation was developed with Geomatrix coating technology in order to obtain constant pharmacokinetics throughout 24 hours. The areas under the curve were not significantly different from those observed with similar doses of ropinirole immediate-release (IR) formulation, administered 3 times a day, but concentration fluctuations were less for ropinirole PR (2-fold vs 5-fold). The efficacy study of the PR versus IR formulations showed non-inferiority of the PR formulation, similar tolerability and feasibility of overnight switches, and indicated that the optimal doses of ropinirole in patients with de novo PD is in the range of 8-12 mg/day. The efficacy study in PD patients with motor fluctuations treated with L-dopa showed that adding ropinirole PR significantly reduced "off" time and increased "on" time in comparison with placebo. The study with ropinirole as an add-on to L-dopa showed a reduced incidence of dyskinesias.