[Portuguese Consensus on the Diagnosis and Management of Lewy Body Dementia (PORTUCALE)]. / Consenso Português para o Diagnóstico e Gestão Clínica da Demência com Corpos de Lewy (PORTUCALE).

Lewy body dementia is a common cause of dementia leading to the progressive deterioration of cognitive function and motor skills, behavioral changes, and loss of autonomy, impairing the quality of life of patients and their families. Even though it is the second leading cause of neurodegenerative dementia, diagnosis is still challenging, due to its heterogenous clinical presentation, especially in the early stages of the disease. Accordingly, Lewy body dementia is often misdiagnosed and clinically mismanaged. The lack of diagnostic accuracy has important implications for patients, given their increased susceptibility to the adverse effects of certain drugs, such as antipsychotics, which may worsen some symptoms associated with Lewy body dementia. Therefore, a specialist consensus based on the analysis of the most updated and relevant literature, and on clinical experience, is useful to all professionals involved in the care of these patients. This work aims to inform and provide recommendations about the best diagnostic and therapeutic approaches in Lewy body dementia in Portugal. Moreover, we suggest some strategies in order to raise the awareness of physicians, policy makers, and the society at large regarding this disease.

A demência com corpos de Lewy é uma causa comum de demência, provocando a perda progressiva de funções cognitivas e capacidades motoras, alterações comportamentais, e perda de autonomia, com compromisso da qualidade de vida dos doentes e seus familiares. Apesar de ser a segunda causa mais frequente de demência neurodegenerativa, o diagnóstico mantém-se um desafio, devido à sua apresentação clínica heterogénea, sobretudo nas fases iniciais da doença. Por conseguinte, a demência com corpos de Lewy é frequentemente mal diagnosticada e clinicamente gerida de forma insuficiente. A falta de acuidade diagnóstica tem implicações significativas para os doentes, dada a maior suscetibilidade aos efeitos adversos de determinados fármacos, tais como os antipsicóticos, que podem agravar alguns sintomas associados à demência com corpos de Lewy. Por conseguinte, um consenso de especialistas, baseado na análise da literatura mais atual e relevante, e na experiência clínica, é útil para todos os profissionais envolvidos no cuidado destes doentes. O objetivo deste trabalho é informar e gerar recomendações acerca das melhores abordagens diagnóstica e terapêutica da demência com corpos de Lewy em Portugal. Além disso, sugerimos estratégias para aumentar a sensibilização dos médicos, dos decisores políticos e da sociedade em geral em relação a esta doença.

End of OSLER Test Sessions in Parkinson's Disease do not Correspond to True Sleep Onset: Results from an Exploratory Study.

The aim of the present study was to evaluate the correlation between the end of an Oxford sleep resistance (OSLER) test session and a neurophysiological marker of sleep onset in Parkinson's disease (PD) patients. Single center study was conducted in PD patients with excessive daytime sleepiness [Epworth sleepiness scale (ESS) >9]. The OSLER test was conducted with a concomitant electroencephalography (EEG), electromyography (mentalis), right and left electroculogram, and video monitoring. Neurophysiological (NP) sleep onset was defined according to AASM criteria (2005). Five PD patients with mean ESS of 14 (10-16) were included. OSLER test duration was shorter than 40 min in all patients (mean duration 20 min and 39 s). No patient fulfilled neurophysiological criteria to sleep onset at the time of OSLER test termination. In 13 OSLER sessions that ended before 40 min, eight had microsleeps in the last 30 s before the end of the test. NP monitoring showed signs of sleepiness in all patients. In PD patients, the early termination of an OSLER test session may not correspond to NP criteria of sleep onset. However, in all PD patients with abnormal OSLER results, there were EEG signs of sleepiness, which do not exclude the potential utility of OSLER test to evaluate the risk of falling asleep.

Quantitative Analysis Versus Visual Assessment of Neuromelanin MR Imaging for the Diagnosis of Parkinson's disease.

BACKGROUND: Specific MR sequences have been able to identify the loss of neuromelanin in the substantia nigra (SN) of early stage Parkinson's disease (PD) patients. Since this technique may have a significant impact in clinical patient management, easy and widely available imaging analysis is needed for routine use. OBJECTIVE: In this study we compared a quantitative analysis with a visual assessment of SN neuromelanin-sensitive MR images in early stage PD patients, in terms of pattern changes recognition and diagnostic accuracy. METHODS: The inclusion criteria were untreated "de novo" PD patients or a 2-5 year PD duration; in addition, age matched controls were enrolled. These were studied with a high-resolution T1-weighted MR imaging sequence at 3.0 Tesla to visualize neuromelanin. The primary outcome was the comparison of quantitative width measurement with visual assessment by experienced neuroradiologists of SN neuromelanin sensitive MR images for PD diagnosis. RESULTS: A total of 12 "de novo" PD patients, 10 PD patients with 2-5 year disease duration and 10 healthy controls were evaluated. We obtained a good accuracy in discriminating early-stage PD patients from controls using either a quantitative width measurement of the T1 high signal or a simple visual image inspection of the SN region. CONCLUSIONS: Visual inspection of neuromelanin-sensitive MR images by experienced neuroradiologists provides comparable results to quantitative width measurement in the detection of early stage PD SN changes and may become a useful tool in clinical practice.

Sleepiness in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease.

OBJECTIVE: To determine whether patients with idiopathic and symptomatic RBD were sleepier than controls, and if sleepiness in idiopathic RBD predicted earlier conversion to Parkinson disease. METHODS: The Epworth Sleepiness Scale (ESS) and its determinants were compared at the time of a video-polysomnography for an RBD diagnosis in patients with idiopathic RBD, in patients with Parkinson disease, and in controls. Whether sleepiness at time of RBD diagnosis predicted an earlier conversion to neurodegenerative diseases was retrospectively analyzed in the followed-up patients. RESULTS: The 75 patients with idiopathic RBD were sleepier (ESS: 7.8 ± 4.6) at the time of RBD diagnosis than 74 age- and sex-matched controls (ESS: 5.0 ± 3.6, P < 0.0001). They reached the levels of 114 patients with Parkinson disease (ESS: 8.7 ± 4.8), whether they had (n = 78) or did not have (n = 36) concomitant RBD. The severity of sleepiness in idiopathic RBD correlated with younger age, but not with sleep measures. Among the 69 patients with idiopathic RBD who were followed up for a median 3 years (1-15 years), 16 (23.2%) developed parkinsonism (n = 6), dementia (n = 6), dementia plus parkinsonism (n = 2), and multiple system atrophy (n = 2). An ESS greater than 8 at time of RBD diagnosis predicted a shorter time to phenoconversion to parkinsonism and dementia, from RBD onset, and from RBD diagnosis (when adjusted for age and time between RBD onset and diagnosis). CONCLUSIONS: Sleepiness is associated with idiopathic REM sleep behavior disorder and predicts more rapid conversion to parkinsonism and dementia, suggesting it is an early marker of neuronal loss in brainstem arousal systems.

Nocturnal agitation in Huntington disease is caused by arousal-related abnormal movements rather than by rapid eye movement sleep behavior disorder.

BACKGROUND: Patients with Huntington disease (HD) and their spouses often complain of agitation during sleep, but the causes are mostly unknown. OBJECTIVE: To evaluate sleep and nocturnal movements in patients with various HD stages and CAG repeats length. METHODS: The clinical features and sleep studies of 29 patients with HD were retrospectively collected (11 referred for genotype-phenotype correlations and 18 for agitation during sleep) and compared with those of 29 age- and sex-matched healthy controls. All patients had videopolysomnography, but the movements during arousals were re-analyzed in six patients with HD with stored video. RESULTS: The patients had a longer total sleep period and REM sleep onset latency, but no other differences in sleep than controls. There was no correlation between CAG repeat length and sleep measures, but total sleep time and sleep efficiency were lower in the subgroup with moderate than milder form of HD. Periodic limb movements and REM sleep behavior disorders were excluded, although 2/29 patients had abnormal REM sleep without atonia. In contrast, they had clumsy and opisthotonos-like movements during arousals from non-REM or REM sleep. Some movements were violent and harmful. They might consist of voluntary movements inappropriately involving the proximal part of the limbs on a background of exaggerated hypotonia. Giant (>65 mcV) sleep spindles were observed in seven (24%) patients with HD and one control. CONCLUSION: The nocturnal agitation in patients with HD seems related to anosognostic voluntary movements on arousals, rather than to REM sleep behavior disorder and other sleep problems.

Substantia nigra neuromelanin-MR imaging differentiates essential tremor from Parkinson's disease.

BACKGROUND: Essential tremor (ET) is a very common movement disorder that has no diagnostic markers. Differentiation with Parkinson's disease (PD) can be clinically challenging in some cases, with a high rate of misdiagnosis. Magnetic resonance imaging (MRI) studies have been able to identify neuromelanin changes in the substantia nigra (SN) of PD patients, but they have thus far not been investigated in ET. In this study, we aimed to characterize neuromelanin-MR signal changes in ET and evaluate its diagnostic accuracy in the differential diagnosis with PD. METHODS: The inclusion criteria were patients with ET and untreated "de novo" PD patients; in addition, age-matched controls were enrolled. These were studied with a high-resolution T1-weighted MRI sequence at 3.0 Tesla to visualize neuromelanin. The primary outcomes were the area and width of the SN region with high signal. RESULTS: A total of 15 ET patients and 12 "de novo" PD patients were evaluated. The area and width of the T1 high signal in the SN region were markedly decreased in the PD group compared with the ET and age-matched controls, and a greater decrease was seen in the ventrolateral segment. The neuromelanin measures in the ET group, although slightly lower, were not significantly different from the healthy control group. We obtained a sensitivity of 66.7% and a specificity of 93.3% in discriminating ET from early-stage PD. CONCLUSIONS: Neuromelanin-sensitive MRI techniques can discriminate ET from early-stage tremor-dominant PD and can be a useful clinical tool in the evaluation of tremor disorders. © 2015 International Parkinson and Movement Disorder Society.

Delayed leukoencephalopathy after acute carbon monoxide intoxication.

Delayed leukoencephalopathy is an uncommon complication of hypoxic-ischemic events of different etiologies, including carbon monoxide intoxication. We present a case of a 40-year-old male patient who was admitted with rapidly progressive neurocognitive and behavioral deficits. There was a history of accidental carbon monoxide intoxication one month before, presenting with loss of consciousness and short hospitalization, followed by a complete clinical recovery. The imaging studies in the delayed phase depicted confluent, symmetric supra-tentorial white matter lesions in keeping with diffuse demyelinization. Restricted diffusion and metabolite abnormalities in magnetic resonance proton spectroscopy were also seen. The diagnosis of CO-mediated delayed post-hypoxic leukoencephalopathy was assumed after exclusion of other mimickers. Hyperbaric oxygen therapy was tentatively performed and the patient had a favorable clinical and radiological evolution.

Spinal cord astrocytoma mimicking multifocal myelitis.

INTRODUCTION: Differential diagnosis of acute/subacute intrinsic spinal cord lesions can be challenging. In addition, intramedullary neoplasms typically show gadolinium enhancement, mass effect, and cord expansion. CASE REPORT: We report a patient with spinal cord and brain stem lesions resembling multifocal myelitis. Magnetic resonance imaging showed no spinal cord enlargement or gadolinium enhancing. Treatment of myelitis was undertaken without stopping the progression of the disease. Biopsy was made and led to a histological diagnosis of astrocytoma. DISCUSSION: Astrocytoma must remain as a possible diagnosis of spinal cord lesions, even without typical characteristics of neoplasms. Furthermore, biopsy should always be considered when diagnosis is uncertain.

Recurrent ischemic stroke in an adult with cystinosis: a clinical-pathological case.

A 32-year-old woman with infantile nephropathic cystinosis presented with cystinosis and recurrent ischemic stroke. The neuropathological description demonstrates that recurrent stroke was caused by intracranial stenosis and showed evidence of cystinosis brain involvement. There are few reports of cerebrovascular disease in patients with longstanding nephropathic cystinosis. This case reinforces that cerebrovascular disease can be a cause of neurological impairment and disability in patients with longstanding nephropathic cystinosis, with implications on primary stroke prevention strategies in these patients.

Chorea-acanthocytosis presenting as motor neuron disease.

INTRODUCTION: Chorea-acanthocytosis (ChAc) is a rare autosomal recessive disease characterized by involuntary movements, seizures, cognitive changes, myopathy, and axonal neuropathy. METHODS: We report a patient who presented with gait impairment and dysarthria. Clinical and neurophysiological assessment disclosed upper and lower motor neuron signs suggestive of motor neuron disease (MND). RESULTS: Later observation of involuntary movements prompted further investigation. Acanthocytes were identified, and the patient's chorein level was low. Genetic studies identified a novel double heterozygous mutation of the chorein gene involving an exon-stop mutation associated with another mutation that can affect the normal splicing of the RNA. CONCLUSIONS: We speculate that this genetic mutation could cause the atypical presentation. ChAc should be included in the differential diagnosis of atypical MND.

Skin cancer and Parkinson's disease.

The report of an increased frequency of melanoma during the clinical development of rasagiline prompted a renewed interest in a possible association between skin cancer and Parkinson's disease (PD). The evaluation of this risk ended in a recommendation to perform a periodic dermatological examination as a follow-up measure of their treatment. The recognition of this safety concern lead to the need to clarify if the risk of skin cancer is indeed associated with PD and if levodopa or other anti-parkinsonian drugs might contribute to increase such risk. To answer these questions, we critically reviewed all clinical studies available concerning the association between skin cancer and PD. We found 26 studies on cancer occurrence in PD. The best data available suggest the risk of cancer is reduced in PD patients. However, specific cancers like thyroid and the female breast were reported at higher-than-expected rates. Additionally, it was suggested that PD patients have a higher frequency of melanoma and non-melanoma skin cancers than the general population. The data on non-melanoma skin cancer are less robust than the data on melanoma. Causal factors remain unknown. Due to the weak association between skin cancer and PD, no robust recommendation can be made regarding the need for periodic dermatological screening.