Amyotrophic lateral sclerosis (ALS) epidemiology has rapidly developed in the last 30 years alongside the evolving changes in concepts in the field of clinical ALS and also due to the recent ...proposals of new classification system for motor neuron diseases. Many of these changes in the clinical scenario have been determined through the results of ALS population-based studies conducted in the last 20 years primarily in Europe. All the evidences converge to show that ALS risk is different across continents and ethnicities. In a European registry consortium named EURALS, ALS incident cases were drawn from a source population comprising almost 24 million people across Europe (ALS cases: 1028) and the estimated incidence was 2.2 per 100,000 person-years (py) for the general population. In contrast, other population-based studies have measured the lowest incidence in East Asia to be 0.89 per 100,000 py and in South Asia to be 0.79 per 100,000 py. A large part of Africa, Latin America and Asia does not have any population-based studies. The origin of geographic difference in ALS incidence is a matter of debate. Probably, this is partly due to genes (C9ORF72) and partly due to environmental risk factors. The rapid disappearance of ALS Foci in Guam, Kii, and West Guinea underline the importance of changes in lifestyle and environmental factors. The Global Burden of Disease, a project aiming to describe the burden of all diseases and injuries across all the countries of the world with a standardized protocol, has collected heterogeneous sources of data to estimate the burden of motor neuron diseases. The demographic changes related to increased expectation of life and the growth of the world population indicate that the load of motor neuron disease is rapidly moving toward 400 thousand prevalent cases. The burden is expected to shift toward Asia and Africa in the next decades for the rapid increase of expectation of life of countries with high demographic impact.
Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional capabilities of older adults to develop a ...coordinated plan to maximize overall health with aging. Specific criteria used by CGA programs to evaluate patients include age, medical comorbidities, psychosocial problems, previous or predicted high healthcare utilization, change in living situation, and specific geriatric conditions. However, no universal criteria have been agreed upon to readily identify patients who are likely to benefit from CGA. Evidence from randomized controlled trials and large systematic reviews and meta-analyses suggested that the healthcare setting may modify the effectiveness of CGA programs. Home CGA programs and CGA performed in the hospital were shown to be consistently beneficial for several health outcomes. In contrast, the data are conflicting for posthospital discharge CGA programs, outpatient CGA consultation, and CGA-based inpatient geriatric consultation services. The effectiveness of CGA programs may be modified also by particular settings or specific clinical conditions, with tailored CGA programs in older frail patients evaluated for preoperative assessment, admitted or discharged from emergency departments and orthogeriatric units or with cancer and cognitive impairment. CGA is capable of effectively exploring multiple domains in older age, being the multidimensional and multidisciplinary tool of choice to determine the clinical profile, the pathologic risk and the residual skills as well as the short- and long-term prognosis to facilitate the clinical decision making on the personalized care plan of older persons.
Age-related hearing impairment (ARHI, also known as presbycusis) is potentially a reversible risk factor for dementia and Alzheimer disease (AD). Social isolation, loneliness, poor verbal ...communication, and cognitive reserve depletion might causally link ARHI with cognitive impairment. ARHI is an important frailty marker, and several factors related to physical frailty could be associated with cognitive impairment. Such factors include inflammatory markers and vascular factors, which might also directly contribute to ARHI. Randomized controlled trials of potential interventions, and larger population-based studies, could facilitate further understanding of the interplay between cognitive impairment, ARHI and frailty in older age. Deficits in both peripheral hearing and central auditory processing (CAP) can contribute to ARHI. Impairments in peripheral hearing and CAP have been linked to accelerated cognitive decline, incident cognitive impairment and AD; moreover, CAP dysfunction is common in mild cognitive impairment (MCI) and AD. Assessment of CAP dysfunction in people with ARHI might, therefore, aid identification of older individuals with increased risk of MCI and AD.
Objective
Current American Academy of Neurology (AAN) guidelines for outcome prediction in comatose survivors of cardiac arrest (CA) have been validated before the therapeutic hypothermia era (TH). ...We undertook this study to verify the prognostic value of clinical and electrophysiological variables in the TH setting.
Methods
A total of 111 consecutive comatose survivors of CA treated with TH were prospectively studied over a 3‐year period. Neurological examination, electroencephalography (EEG), and somatosensory evoked potentials (SSEP) were performed immediately after TH, at normothermia and off sedation. Neurological recovery was assessed at 3 to 6 months, using Cerebral Performance Categories (CPC).
Results
Three clinical variables, assessed within 72 hours after CA, showed higher false‐positive mortality predictions as compared with the AAN guidelines: incomplete brainstem reflexes recovery (4% vs 0%), myoclonus (7% vs 0%), and absent motor response to pain (24% vs 0%). Furthermore, unreactive EEG background was incompatible with good long‐term neurological recovery (CPC 1–2) and strongly associated with in‐hospital mortality (adjusted odds ratio for death, 15.4; 95% confidence interval, 3.3–71.9). The presence of at least 2 independent predictors out of 4 (incomplete brainstem reflexes, myoclonus, unreactive EEG, and absent cortical SSEP) accurately predicted poor long‐term neurological recovery (positive predictive value = 1.00); EEG reactivity significantly improved the prognostication.
Interpretation
Our data show that TH may modify outcome prediction after CA, implying that some clinical features should be interpreted with more caution in this setting as compared with the AAN guidelines. EEG background reactivity is useful in determining the prognosis after CA treated with TH. ANN NEUROL 2010;67:301–307
Parkinson disease (PD) is of unknown but presumably multifactorial etiology. Neuropathologic studies and animal models show that exposure to environmental neurotoxicants can determine progressive ...damage in the substantia nigra many years before the onset of clinical parkinsonism. Therefore, PD, like other neurologic diseases related to aging, may be determined by exposures present in the environment early during the life span or even during pregnancy. Recent epidemiologic studies have focused on the possible role of environmental risk factors present during adult life or aging. Smoking and coffee drinking have consistently been identified to have protective associations, whereas roles of other risk factors such as pesticide and infections have been reported in some studies but not replicated in others. Both genetic inheritance and sharing of common environment in the same family explain the increased risk of PD of relatives of PD cases compared with relatives of controls in familial aggregation studies. Much evidence indicates that risk factors that have a long latency or a slow effect could be important for late-onset PD. Further epidemiologic studies are warranted in this area.
To assess the worldwide variation of amyotrophic lateral sclerosis (ALS) incidence, we performed a systematic review and meta-analysis of population-based data published to date.
We reviewed Medline ...and Embase up to June 2015 and included all population-based studies of newly diagnosed ALS cases, using multiple sources for case ascertainment. ALS crude and standardized incidence (on age and sex using the US 2010 population) were calculated. Random effect meta-analysis and meta-regression were performed using the subcontinent as the main study level covariate. Sources of heterogeneity related to the characteristics of the study population and the study methodology were investigated.
Among 3216 records, 44 studies were selected, covering 45 geographical areas in 11 sub-continents. A total of 13 146 ALS cases and 825 million person-years of follow-up (PYFU) were co-nsidered. The overall pooled worldwide crude ALS incidence was at 1.75 (1.55-1.96)/100 000 PYFU; 1.68 (1.50-1.85)/100 000 PYFU after standardization. Heterogeneity was identified in ALS standardized incidence between North Europe 1.89 (1.46-2.32)/100 000 PYFU and East Asia 0.83 (0.42-1.24)/100 000 PYFU, China and Japan P = 0.001 or South Asia 0.73 (0.58-0.89)/100 000/PYFU Iran, P = 0.02. Conversely, homogeneous rates have been reported in populations from Europe, North America and New Zealand pooled ALS standardized incidence of 1.81 (1.66-1.97)/100 000 PYFU for those areas.
This review confirms a heterogeneous distribution worldwide of ALS, and sets the scene to sustain a collaborative study involving a wide international consortium to investigate the link between ancestry, environment and ALS incidence.
Summary
Purpose: Status epilepticus (SE) that is resistant to two antiepileptic compounds is defined as refractory status epilepticus (RSE). In the few available retrospective studies, estimated RSE ...frequency is between 31% and 43% of patients presenting an SE episode; almost all seem to require a coma induction for treatment. We prospectively assessed RSE frequency, clinical predictors, and outcome in a tertiary clinical setting.
Methods: Over 2 years we collected 128 consecutives SE episodes (118 patients) in adults. Clinical data and their relationship to outcome (mortality and return to baseline clinical conditions) were analyzed.
Results: Twenty‐nine of 128 SE episodes (22.6%) were refractory to first‐ and second‐line antiepileptic treatments. Severity of consciousness impairment and de novo episodes were independent predictors of RSE. RSE showed a worse outcome than non‐RSE (39% vs. 11% for mortality; 21% vs. 63% for return to baseline clinical conditions). Only 12 patients with RSE (41%) required coma induction for treatment.
Discussion: This prospective study identifies clinical factors predicting the onset of SE refractoriness. RSE appears to be less frequent than previously reported in retrospective studies; furthermore, most RSE episodes were treated outside the intensive care unit (ICU). Nonetheless, we confirm that RSE is characterized by high mortality and morbidity.
Summary
Since previous reviews of epidemiologic studies of premature mortality among people with epilepsy were completed several years ago, a large body of new evidence about this subject has been ...published. We aim to update prior reviews of mortality in epilepsy and to reevaluate and quantify the risks, potential risk factors, and causes of these deaths. We systematically searched the Medline and Embase databases to identify published reports describing mortality risks in cohorts and populations of people with epilepsy. We reviewed relevant reports and applied criteria to identify those studies likely to accurately quantify these risks in representative populations. From these we extracted and summarized the reported data. All population‐based studies reported an increased risk of premature mortality among people with epilepsy compared to general populations. Standard mortality ratios are especially high among people with epilepsy aged <50 years, among those whose epilepsy is categorized as structural/metabolic, those whose seizures do not fully remit under treatment, and those with convulsive seizures. Among deaths directly attributable to epilepsy or seizures, important immediate causes include sudden unexpected death in epilepsy (SUDEP), status epilepticus, unintentional injuries, and suicide. Epilepsy‐associated premature mortality imposes a significant public health burden, and many of the specific causes of death are potentially preventable. These require increased attention from healthcare providers, researchers, and public health professionals.
Irisin, the circulating peptide originating from fibronectin type III domain-containing protein 5 (FNDC5), is mainly expressed by muscle fibers under peroxisome proliferator-activated receptor gamma ...coactivator 1-alpha PGC1α control during exercise. In addition to several beneficial effects on health, physical activity positively affects nervous system functioning, particularly the hippocampus, resulting in amelioration of cognition impairments. Recently, FNDC5/irisin detection in hippocampal neurons and the presence of irisin in the cerebrospinal fluid opened a new intriguing chapter in irisin history. Interestingly, in the hippocampus of mice, exercise increases FNDC5 levels and upregulates brain-derived neurotrophic factor (BDNF) expression. BDNF, displaying neuroprotection and anti-inflammatory effects, is mainly produced by microglia and astrocytes. In this review, we discuss how these glial cells can morphologically and functionally switch during neuroinflammation by modulating the expression of a plethora of neuroprotective or neurotoxic factors. We also focus on studies investigating the irisin role in neurodegenerative diseases (ND). The emerging involvement of irisin as a mediator of the multiple positive effects of exercise on the brain needs further studies to better deepen this issue and the potential use in therapeutic approaches for neuroinflammation and ND.
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