Clinicians' ability to diagnose dementia with Lewy bodies is not affected by ß-amyloid load.

OBJECTIVE: To investigate whether an increasing load of ß-amyloid and/or neuritic plaques influences the phenotype, and thus the clinical diagnostic accuracy, of dementia with Lewy bodies (DLB). METHODS: A series of 64 subjects with autopsy-proven DLB was studied. Last diagnosis before death was used to determine the clinical diagnostic accuracy of DLB in relation to Lewy body distribution and extent of Alzheimer ß-amyloid and/or neuritic pathology. DLB pathologic diagnosis was made according to consensus criteria, using α-synuclein immunostaining for Lewy body identification. ß-Amyloid immunostaining was used for quantifying ß-amyloid deposits. The Consortium to Establish a Registry for Alzheimer's Disease criteria and Braak stage were applied for semiquantitative grading of neuritic plaque and neurofibrillary tangle pathology. RESULTS: Overall clinical diagnostic accuracy for the entire DLB cohort was high (80%), reflecting the high prevalence of core clinical features (fluctuations [81%], parkinsonism [77%], visual hallucinations [70%]). Lower frequencies of core clinical features of DLB, resulting in lower accuracy of its clinical diagnosis, were associated with decreasing Lewy body distribution (p < 0.0001) and with increasing neuritic plaque pathology (p = 0.035), but not with the number of ß-amyloid plaque deposits. CONCLUSIONS: The likelihood of occurrence of the DLB clinical syndrome is positively related to the extent of Lewy body pathology and negatively related to the severity of Alzheimer neuritic pathology, while ß-amyloid load has no effect.

Jóvenes indígenas en la frontera: relaciones entre etnicidad, escolaridad y territorialidad / Young indigenous people on the boundaries: relationships between ethnicity, schooling and territoriality

Desde una perspectiva etnográfica, se analizan dos escenarios que ubican a los jóvenes indígenas ante situaciones fronterizas. Por un lado, la condición de habitar en los límites geográficos y administrativos que separan a los Estados nacionales. Por el otro, se aborda la escolaridad formal entendiéndola como un espacio de transición o frontera.Planteamos que la frontera, en tanto categoría analítica, se ha convertido en una herramienta teórica colmada de tensiones en las ciencias sociales, por lo que se propone un acercamiento particular desde la Antropología Social. Se ilustran las reflexiones con registros obtenidos a partir del trabajo de campo realizado en comunidades indígenas wichí (Argentina) en el marco de un investigación cualitativa que tiene por objetivo conocer los sentidos que guarda la educación formal para los jóvenes indígenas. Como resultado de la investigación se destaca la generación de conocimientos sobre la escolaridad obligatoria de los pueblos indígenas desde la perspectiva de los actores involucrados.

Epileptic mechanisms in Charles Bonnet syndrome.

Epileptic phenomena are usually not considered a possible cause of prolonged hallucinatory states such as Charles Bonnet syndrome (CBS). A 65-year-old woman with previous right hemorrhagic strokes developed complex visual hallucinations (CVHs), featuring CBS, and delayed palinopsic phenomena, along with new neurological signs and worsening of existing deficits. Video/EEG/polygraphy monitoring revealed the presence of right-sided periodic lateralized epileptiform discharges of the "plus" type (PLEDs plus) and documented a focal seizure in close relation to a delayed palinopsia episode. Adjustment of antiepileptic drug treatment led to remission of the CVHs with simultaneous disappearance of PLEDs plus and epileptic seizures and return to previous neurological status. We discuss the role of continuous (PLEDs plus) and intermittent (focal seizures) epileptic activities in this episodic form of CBS, considering current theories on the genesis of CVHs. EEG assessment is recommended if CBS develops in a patient with unexplained worsening of existing neurological signs.

Focal epileptic seizures mimicking sleep paralysis.

Sleep paralysis (SP) is a common parasomnia. The diagnostic criteria for SP, as reported in the International Classification of Sleep Disorders, are essentially clinical, as electroencephalography (EEG)-polysomnography (PSG) is not mandatory. We describe a subject whose sleep-related events fulfilled the diagnostic criteria for SP, even though her visual hallucinations were elementary, repetitive and stereotyped, thus differing from those usually reported by patients with SP. Video/EEG-PSG documented the focal epileptic nature of the SP-like episodes.

Macrogol for the treatment of constipation in Parkinson's disease. A randomized placebo-controlled study.

Chronic constipation is the most frequent symptom of autonomic system involvement in Parkinson's disease (PD). Quite often the symptom is severe and impairs patients' quality of life. The objective of this study is to determine the efficacy and safety of an isosmotic macrogol solution for the treatment of constipation in PD patients, in a double-blind, placebo-controlled study. A total of 57 PD patients with constipation were randomly assigned to receive an isosmotic macrogol electrolyte solution (MC-ES; 29 patients) or placebo (28 patients) for 8 weeks. Treatment efficacy was defined as complete relief of the symptom or a marked improvement of two of the following indicators: stool frequency, straining, stool consistency, use of rectal laxatives as a rescue therapy. The responder rates were significantly higher in the MC-ES group both at the first (4 weeks; P < 0.0003) and at the final evaluation (8 weeks; P < 0.0012). The frequency of bowel movements (P < 0.002) and stool consistency (P < 0.006) were significantly changed in the MC-ES group compared to the placebo group. At the final evaluation, a rectal laxative was used by 2 (12.5%) patients on placebo, whereas no use was recorded in the MC-ES group. Responder rate for straining showed a favorable trend in patients treated with macrogol versus placebo. Unified Parkinson's Disease Rating Scale Part III and Parkinson's Disease Questionnaire (PDQ-39) did not show any significant modification in either group during the 8-week treatment period. The results of this placebo-controlled study show the efficacy of MC-ES in the treatment of constipation in PD. MC-ES was well-tolerated and did not affect the course of PD.

Relationship between hallucinations, delusions, and rapid eye movement sleep behavior disorder in Parkinson's disease.

Psychotic symptoms are the main and the most disabling "nonmotor" complications of Parkinson's disease (PD), the pathophysiology of which is poorly recognized. Polysomnographic studies have shown a relationship between visual hallucinations and rapid eye movement (REM) sleep. The objective of this study is to clarify the relationship between psychotic symptoms and REM sleep behavior disorder (RBD) in PD. In a Parkinson's disease outpatient unit, 289 consecutive subjects with idiopathic PD were administered (in the period from January to December 2002) a multiple-choice questionnaire and structured interview on sleep and mental disorders. RBD was diagnosed in accordance with the minimal diagnostic criteria of the International Classification of Sleep Disorders. Hallucinations and delusional disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders-IV criteria. The presence or absence of psychotic symptoms, of RBD, and of daytime sleepiness, as well as motor status, cognitive status, and mood were assessed. Approximately 32% (n = 92) of the subjects presented with psychotic disorders; 30% (n = 86) had experienced hallucinations; 2% (n = 6) had delusions without hallucinations. Sixty-two (72%) hallucinators reported nocturnal hallucinations. A total of 6.6% (n = 19) of the subjects complained of a delusional disorder. There were 26.6% (n = 77) of subjects who presented with RBD: 28 (36%) with onset before and 49 (63%) with onset after PD diagnosis. The presence of RBD was associated with an increased risk of manifesting hallucinations and delusions (odds ratio [OR], 2.73). Other independent clinical factors found to have an effect on psychotic disorders were cognitive impairment (OR, 3.92), disease duration (OR, 2.46), advanced age (OR, 2.34), and severity of motor symptoms (OR, 2.06). These results suggest that RBD is widely associated with psychosis in PD.

A questionnaire on sleep and mental disorders in Parkinson's disease (QSMDPD): development and application of a new screening tool.

Psychiatric, cognitive and sleep disorders are the most frequent and disabling non-motor complications of Parkinson's disease (PD). To improve the description of sleep and mental disorders in PD patients, we set out to develop a simple and reliable data collection tool (questionnaire) for the screening of large samples of PD patients. The first draft of the questionnaire was administered to a consecutive series of 120 PD patients from the outpatient department of our unit, who were instructed to fill it in with the help of their caregivers. Subsequent drafts of the questionnaire were evaluated together with the patients and their caregivers, until a final, satisfactory version was obtained. This final version was named the Questionnaire on Sleep and Mental Disorders in PD (QSMDPD). This questionnaire--we used the Italian version, named Questionario sui Disturbi del Sonno e Mentali nella Malattia di Parkinson, ODSMMP--consists of 119 questions with multiple-choice answers. The QSMDPD was mailed or handed to 400 PD patients followed at our unit's outpatient department. Three hundred and twenty (80%) were returned to us. A review of these completed questionnaires, conducted by a neurologist together with the patients, showed 90% of them (289) to be complete and to provide reliable data. This high compliance suggests that the QSMDPD is a promising tool for collecting data on sleep and mental disorders in large samples of PD patients. A short version will be administered as a follow-up tool.

Dopaminergic modulation of apoptosis in human peripheral blood mononuclear cells: possible relevance for Parkinson's disease.

Dopamine (DA) modulates apoptosis in neuronal and non-neuronal cells, and dopaminergic pathways contribute to neurodegenerative disease. Human lymphocytes express dopaminergic receptors and DA transporters, and synthesize endogenous catecholamines, which may modulate apoptosis in these cells. In the present study, dopaminergic modulation of apoptosis was investigated in human peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. Twenty-four-hour DA reduced at 0.1-5 x 3 10(-6) M and enhanced at 1-5 x 310(-4) M spontaneous apoptosis. DA 1 x 310(-6) M was inhibited by the D1-like receptor antagonist SCH 23390 1 x 310(-6) M, but not by the D2-like receptor antagonists domperidone 1 x 3 10(-6) M or haloperidol 1 x 3 10(-6) M, while the effect of DA 5 x 3 10(-4) M was prevented by the antioxidants glutathione 5-10 mM or N-acetyl-l-cysteine 1-10 mM. Intracellular reactive oxygen species were respectively reduced and increased by 1-3 h incubation with DA 0.1-10 x 3 10(-6) M and 1-5x310(-4) M. Twenty-four-hour DA 1 x 3 10(-6) M or 5 x 3 10(-4) M had no effect on PBMC expression of Cu/Zn superoxide dismutase or Bcl-2; however, DA 5 x 3 10(-4) M decreased caspase-3 activity. In human PBMCs, DA seems to promote apoptosis through oxidative mechanisms but may also result in cell rescue from apoptotic death possibly through activation of D1-like receptors. The dual effect of DA on human PBMCs closely resembles that on striatal neurons. Lymphocytes of patients with Parkinson's disease may show reduced DA content and impaired DA transporter immunoreactivity. Human PBMCs may thus represent a simple and readily accessible model to study DA-related mechanisms relevant for neurodegenerative disease.