Animal Approaches to Studying Risk Factors for Parkinson's Disease: A Narrative Review.

Despite recent efforts to search for biomarkers for the pre-symptomatic diagnosis of Parkinson's disease (PD), the presence of risk factors, prodromal signs, and family history still support the classification of individuals at risk for this disease. Human epidemiological studies are useful in this search but fail to provide causality. The study of well-known risk factors for PD in animal models can help elucidate mechanisms related to the disease's etiology and contribute to future prevention or treatment approaches. This narrative review aims to discuss animal studies that investigated four of the main risk factors and/or prodromal signs related to PD: advanced age, male sex, sleep alterations, and depression. Different databases were used to search the studies, which were included based on their relevance to the topic. Although still in a reduced number, such studies are of great relevance in the search for evidence that leads to a possible early diagnosis and improvements in methods of prevention and treatment.

Curcumin-Loaded Mesoporous Silica Nanoparticles Dispersed in Thermo-Responsive Hydrogel as Potential Alzheimer Disease Therapy.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive and behavioral impairment. Curcumin-loaded mesoporous silica nanoparticles (MSN-CCM) can overcome the drawbacks related to the free curcumin (CCM) clinical application, such as water insolubility and low bioavailability, besides acting over the main causes associated to AD. A thermo-responsive hydrogel is an interesting approach for facilitating the administration of the nanosystem via a nasal route, as well as for overcoming mucociliary clearance mechanisms. In light of this, MSN-CCM were dispersed in the hydrogel and evaluated through in vitro and in vivo assays. The MSNs and MSN-CCM were successfully characterized by physicochemical analysis and a high value of the CCM encapsulation efficiency (EE%, 87.70 ± 0.05) was achieved. The designed thermo-responsive hydrogel (HG) was characterized by rheology, texture profile analysis, and ex vivo mucoadhesion, showing excellent mechanical and mucoadhesive properties. Ex vivo permeation studies of MSN-CCM and HG@MSN-CCM showed high permeation values (12.46 ± 1.08 and 28.40 ± 1.88 µg cm-2 of CCM, respectively) in porcine nasal mucosa. In vivo studies performed in a streptozotocin-induced AD model confirmed that HG@MSN-CCM reverted the cognitive deficit in mice, acting as a potential formulation in the treatment of AD.

Progressive spastic tetraplegia and axial hypotonia (STAHP) due to SOD1 deficiency: is it really a new entity?

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rare, progressive, and fatal neurodegenerative disease due to upper and lower motor neuron involvement with symptoms classically occurring in adulthood with an increasing recognition of juvenile presentations and childhood neurodegenerative disorders caused by genetic variants in genes related to Amyotrophic Lateral Sclerosis. The main objective of this study is detail clinical, radiological, neurophysiological, and genetic findings of a Brazilian cohort of patients with a recent described condition known as Spastic Tetraplegia and Axial Hypotonia (STAHP) due to SOD1 deficiency and compare with other cases described in the literature and discuss whether the clinical picture related to SOD1 protein deficiency is a new entity or may be represent a very early-onset form of Amyotrophic Lateral Sclerosis. METHODS: We conducted a case series report which included retrospective data from five Brazilian patients with SOD1 protein deficiency of a Brazilian reference center for Neuromuscular Disorders. Clinical data were obtained from a review of the medical records and descriptive statistics and variables were summarized using counts and percentages of the total population. RESULTS: All 5 patients presented with a childhood-onset neurodegenerative disorders characterized by spastic tetraplegia with axial hypotonia in all cases, with gestational history showing polyhydramnios in 4/5 and intrauterine growth restriction in 3/5 patients, with most patients initially presenting a normal motor development until the six month of life or during the first year followed by a rapidly progressive motor decline with severe dysphagia and respiratory insufficiency in all patients accompanied by cognitive impairment in 3/5 patients. All patients were homozygous for the c.335dupG (p.Cys112Trpfs*11) mutation in the SOD1 gene with completely decreased enzyme activity. CONCLUSIONS: This case series is the biggest data collection of the new recent clinical entity described as Spastic Tetraplegia and Axial Hypotonia (STAHP) due to SOD1 deficiency.

The Renin-Angiotensin System in Huntington's Disease: Villain or Hero?

Huntington's Disease (HD) is an autosomal dominant, progressive neurodegenerative disorder characterized by severe symptoms, including motor impairment, cognitive decline, and psychiatric alterations. Several systems, molecules, and mediators have been associated with the pathophysiology of HD. Among these, there is the Renin-Angiotensin System (RAS), a peptide hormone system that has been associated with the pathology of neuropsychiatric and neurodegenerative disorders. Important alterations in this system have been demonstrated in HD. However, the role of RAS components in HD is still unclear and needs further investigation. Nonetheless, modulation of the RAS components may represent a potential therapeutic strategy for the treatment of HD.

Intracerebroventricular injection of deltamethrin increases locomotion activity and causes spatial working memory and dopaminergic pathway impairment in rats.

Deltamethrin (DM) is widely used in agriculture, veterinary medicine and control of domestic pests. Epidemiological studies suggest that DM exposure is a risk factor for neurodegenerative disorders such as Parkinson's (PD) and Alzheimer diseases; however the mechanisms are elusive. In the present study we evaluated the effects of intracerebroventricular (i.c.v.) administration of DM on locomotion activity, spatial working memory and dopaminergic pathway in the rat. Middle-aged male Wistar rats received three i.c.v. injections of DM 0.5 µg, DM 5 µg or vehicle, every other day. Across the treatment, the animals were submitted to behavioral evaluation in the catalepsy test, open field test, and spontaneous alternation task. Following completion of behavioral tests, rats were perfused and their brains were processed to tyrosine hydroxylase (TH) immunohistochemistry. We observed that i.c.v. administration of DM 5 µg increased locomotion activity (open field) and caused spatial working memory impairment (spontaneous alternation task). These alterations were accompanied by reduction TH immunoreactivity in the substantia nigra pars compacta (SNpc), ventral tegmental area (VTA) and dorsal striatum. Conversely, no motor change was observed in the catalepsy test. These results indicate that i.c.v. administration of DM can cause hyperactivity and cognitive alteration which may be related to disruption of the dopaminergic pathway.

Cannabidiol Partially Blocks the Excessive Sleepiness in Hypocretindeficient Rats: Preliminary Data.

BACKGROUND: Excessive daytime sleepiness and cataplexy are among the symptoms of narcolepsy, a sleep disorder caused by the loss of hypocretin/orexin (HCRT/OX) neurons placed into the Hypothalamus (LH). Several treatments for managing narcolepsy include diverse drugs to induce alertness, such as antidepressants, amphetamine, or modafinil, etc. Recent evidence has shown that cannabidiol (CBD), a non-psychotropic derived from Cannabis sativa, shows positive therapeutic effects in neurodegenerative disorders, including Parkinson´s disease. Furthermore, CBD provokes alertness and enhances wake-related neurochemicals in laboratory animals. Thus, it is plausible to hypothesize that excessive somnolence observed in narcolepsy might be blocked by CBD. OBJECTIVE: Here, we determined whether the systemic injection of CBD (5mg/kg, i.p.) would block the excessive sleepiness in a narcoleptic model. METHODS: To test this idea, the neurotoxin hypocretin-2-saporin (HCRT2/SAP) was bilaterally injected into the LH of rats to eliminate HCRT leading to the establishment of narcoleptic-like behavior. Since excessive somnolence in HCRT2/SAP lesioned rats has been observed during the lights-off period, CBD was administered at the beginning of the dark phase. RESULTS: Hourly analysis of sleep data showed that CBD blocked the sleepiness during the lights-off period across 7h post-injection in lesioned rats. CONCLUSION: Taking together, these preliminary findings suggest that CBD might prevent sleepiness in narcolepsy.

Aluminum affects neural phenotype determination of embryonic neural progenitor cells.

Aluminum (Al) is a neurotoxin and is associated with the etiology of neurodegenerative diseases, such as Alzheimer's disease (AD). The Al-free ion (Al3+) is the biologically reactive and toxic form. However, the underlying mechanisms of Al toxicity in the brain remain unclear. Here, we evaluated the effects of Al3+ (in the chloride form-AlCl3) at different concentrations (0.1-100 µM) on the morphology, proliferation, apoptosis, migration and differentiation of neural progenitor cells (NPCs) isolated from embryonic telencephalons, cultured as neurospheres. Our results reveal that Al3+ at 100 µM reduced the number and diameter of neurospheres. Cell cycle analysis showed that Al3+ had a decisive function in proliferation inhibition of NPCs during neural differentiation and induced apoptosis on neurospheres. In addition, 1 µM Al3+ resulted in deleterious effects on neural phenotype determination. Flow cytometry and immunocytochemistry analysis showed that Al3+ promoted a decrease in immature neuronal marker ß3-tubulin expression and an increase in co-expression of the NPC marker nestin and glial fibrillary acidic protein. Thus, our findings indicate that Al3+ caused cellular damage and reduced proliferation and migration, resulting in global inhibition of NPC differentiation and neurogenesis.

The effects of retinol oral supplementation in 6-hydroxydopamine dopaminergic denervation model in Wistar rats.

Vitamin A (retinol) is involved in signaling pathways regulating gene expression and was postulated to be a major antioxidant and anti-inflammatory compound of the diet. Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by loss of nigral dopaminergic neurons, involving oxidative stress and pro-inflammatory activation. The aim of the present study was to evaluate the neuroprotective effects of retinol oral supplementation against 6-hydroxydopamine (6-OHDA, 12 µg per rat) nigrostriatal dopaminergic denervation in Wistar rats. Animals supplemented with retinol (retinyl palmitate, 3000 IU/kg/day) during 28 days exhibited increased retinol content in liver, although circulating retinol levels (serum) were unaltered. Retinol supplementation did not protect against the loss of dopaminergic neurons (assessed through tyrosine hydroxylase immunofluorescence and Western blot). Retinol supplementation prevented the effect of 6-OHDA on Iba-1 levels but had no effect on 6-OHDA-induced GFAP increase. Moreover, GFAP levels were increased by retinol supplementation alone. Rats pre-treated with retinol did not present oxidative damage or thiol redox modifications in liver, and the circulating levels of TNF-α, IL-1ß, IL-6 and IL-10 were unaltered by retinol supplementation, demonstrating that the protocol used here did not cause systemic toxicity to animals. Our results indicate that oral retinol supplementation is not able to protect against 6-OHDA-induced dopaminergic denervation, and it may actually stimulate astrocyte reactivity without altering parameters of systemic toxicity.

Age-Related Changes in the Behavior of Apolipoprotein E Knockout Mice.

The knockout mouse model, B6.129P2-Apoetm1Unc is homozygotic for the Apolipoprotein E (ApoE) deletion; thus, it is capable of developing hyperlipidemia and atherosclerosis but ApoE is also a lipid-transport protein abundantly expressed in most neurons in the central nervous system, so these animals could also be models of neurodegenerative diseases. The aim of this study was to determine age-related changes in spontaneous behavior and in learning and memory of Apolipoprotein E knockout mice. Spontaneous behavioral measurements included sleeping pattern, motor coordination and balance by rotarod and open field activity, whereas learning and memory tests included forced alternation in Y-maze, novel object recognition and passive avoidance conditioning. Significant behavioral differences between aged knockout mice and age-matched wild type strain, C57Bl/6 were found in all the behavioral tests, except for the rotarod test. Genetically' modified mice exhibited less huddling contact during sleeping, decreased locomotor activity in novel environments and in learning and memory deficits. These results are consistent with the cognitive impairment and memory loss seen as the earliest clinical symptoms in neurodegenerative disorders such as Alzheimer's disease. The ApoE knockout mice might therefore be an appropriate model for studying the underlying mechanisms involved in behavioral changes caused by neurodegenerative diseases as well as for evaluating new therapies for these pathologies.

Síntomas no motores en pacientes con enfermedad de Parkinson / Non motor symptoms in patients with Parkinson´s disease

Se realizó un estudio prospectivo de 44 pacientes con enfermedad de Parkinson, atendidos en la consulta de Trastornos del Movimiento del Hospital Provincial Docente Clinicoquirúrgico Saturnino Lora Torres de Santiago de Cuba, desde agosto de 2013 hasta julio de 2015, con vistas a determinar la frecuencia de aparición de síntomas no motores. Entre los más frecuentes figuraron los siguientes: depresión (72,7 por ciento), nicturia (68,2 por ciento), ansiedad (54,6 por ciento), síndrome de piernas inquietas (50,0 por ciento), estreñimiento (47,7 por ciento) e insomnio (40,9 por ciento), por citar algunos. Cabe destacar que 95,5 por ciento de los afectados presentó algún síntoma y el promedio por paciente fue de 7,45, con menor aparición durante el primer año de la enfermedad

A prospective study of 44 patients with Parkinson´s disease assisted in the service for movement disorders of Saturnino Lora Torres Teaching Clinical Surgical Provincial Hospital in Santiago de Cuba, was carried out from August, 2013 to July, 2015, aimed at determining the emergence frequency of non motors symptoms. Among the most frequent symptoms there were: depression (72.7 percent), nicturia (68.2 percent), anxiety (54.6 percent), restless legs syndrome (50.0 percent), constipation (47.7 percent) and insomnia (40.9 percent), just to mention some of them. It is necessary to highlight that 95.5 percent of the affected patients presented some symptom and the average for patient was 7.45, with less emergence during the first year of the disease

Presentación atípica de la enfermedad de Alexander infantil sin macrocefalia / An atypical presentation of Infantile Alexander disease lacking macrocephaly

Resumen: Introducción: La enfermedad de Alexander consiste en una forma de leucodistrofia poco frecuente que afecta principalmente a los astrocitos; tiene un patrón de herencia autosómica recesiva y es causada por mutaciones en el gen GFAP, localizado en el cromosoma 17q21. Puede presentarse a cualquier edad y la forma infantil se caracteriza por macrocefalia, crisis convulsivas, retraso motor y cognitivo grave y espasticidad o ataxia progresivas. Caso clínico: Paciente de sexo femenino de 8 meses evaluada por retraso psicomotor y crisis convulsivas motoras focales no provocadas. En la exploración física, con perímetro cefálico normal, respuesta motora incrementada ante estímulos táctiles y al ruido, signos piramidales y ausencia de visceromegalias. Se observó hipodensidad generalizada de la sustancia blanca en la resonancia magnética y punción lumbar con hiperproteinorraquia. Se descartó enfermedad de Krabbe mediante ensayo enzimático y secuenciación del gen GALC. En la reevaluación del caso, las alteraciones en la neuroimagen hicieron sospechar de enfermedad de Alexander, y la secuenciación del gen GFAP reportó una mutación en el exón 4 c.716G > A, lo que ocasionó un cambio de arginina por histidina en la posición 239 de la proteína (p.Arg239His). Conclusiones: Los signos radiológicos en la resonancia fueron determinantes para el diagnóstico, que posteriormente se confirmó con estudio molecular. Es importante considerar que ciertas mutaciones no se asocian con macrocefalia, lo cual puede ocasionar retraso en el diagnóstico.

Abstract: Background: Alexander disease is a rare form of leukodystrophy that involves mainly astrocytes; it is inherited in an autosomal recessive manner and occurs by mutations in the GFAP gene, located on chromosome 17q21. It can occur at any age and its infantile form is characterized by macrocephaly, seizures, severe motor and cognitive delay, and progressive spasticity or ataxia. Case report: An 8-month-old female was evaluated with a history of neurodevelopmental delay and unprovoked focal motor seizures. Physical examination showed normal head circumference, increased motor responses to tactile and noise stimuli, pyramidal signs and no visceromegalies. Widespread hypodense white matter was found on magnetic resonance and lumbar puncture showed hyperproteinorrachia. Krabbe disease was ruled out by enzymatic assay and gene sequencing of GALC. In the reassessment of the case, abnormalities in neuroimaging lead to suspicion of Alexander disease, and GFAP gene sequencing reported a pathogenic mutation in exon 4 c.716G > A, which caused a change of arginine to histidine at position 239 of the protein (p.Arg239His). Conclusions: The radiographic signs observed in the resonance were decisive for the diagnosis, later confirmed by molecular study. It is important to consider that certain mutations are not associated with macrocephaly, which may cause delay in diagnosis.

[An atypical presentation of Infantile Alexander disease lacking macrocephaly]. / Presentación atípica de la enfermedad de Alexander infantil sin macrocefalia.

BACKGROUND: Alexander disease is a rare form of leukodystrophy that involves mainly astrocytes; it is inherited in an autosomal recessive manner and occurs by mutations in the GFAP gene, located on chromosome 17q21. It can occur at any age and its infantile form is characterized by macrocephaly, seizures, severe motor and cognitive delay, and progressive spasticity or ataxia. CASE REPORT: An 8-month-old female was evaluated with a history of neurodevelopmental delay and unprovoked focal motor seizures. Physical examination showed normal head circumference, increased motor responses to tactile and noise stimuli, pyramidal signs and no visceromegalies. Widespread hypodense white matter was found on magnetic resonance and lumbar puncture showed hyperproteinorrachia. Krabbe disease was ruled out by enzymatic assay and gene sequencing of GALC. In the reassessment of the case, abnormalities in neuroimaging lead to suspicion of Alexander disease, and GFAP gene sequencing reported a pathogenic mutation in exon 4 c.716G>A, which caused a change of arginine to histidine at position 239 of the protein (p.Arg239His). CONCLUSIONS: The radiographic signs observed in the resonance were decisive for the diagnosis, later confirmed by molecular study. It is important to consider that certain mutations are not associated with macrocephaly, which may cause delay in diagnosis.

Elevated ferric, calcium and magnesium ions in the brain induce protein aggregation in brain mitochondria / El aumento de iones férricos, calcio y magnesio en el cerebro induce la agregación de proteínas en las mitocondrias del cerebro

OBJECTIVE: Alzheimer s disease and Parkinson s disease are two of several neurodegenerative disorders that affect the elderly. Although their aetiology remains uncertain, studies suggest that elevated aluminium or other metal ions in the brain directly influence the development of the histological abnormalities normally associated with these diseases; other investigations suggest that metal-ion-induced-dysfunction of mitochondria might be a critical factor. METHODS: In this study, the impact of elevated aluminum (Al3+), ferric (Fe3+), calcium (Ca2+) and magnesium (Mg2+) ions on brain histology and on the protein composition of brain mitochondria were evaluated. Rabbits were injected intra-cerebrally with 1.4% solutions of either aluminium chloride (AlCl3), ferric chloride (FeCl2), calcium chloride (CaCl2) or magnesium chloride (MgCl2) and sacrificed 10 days later. RESULTS: Histological analysis revealed that Al3+ but not the other ions induced neurofibrillary degeneration within the midbrain and medulla. Alternatively, SDS-PAGE revealed that Fe3+, Ca2+ and Mg2+ but not Al3+ induced alterations to the distribution of brain mitochondrial proteins. Both Fe3+ and Ca2+ triggered decreased concentration of three low molecular weight proteins (~7-14 kd) but Ca precipitated their total absence. Both ions led to increased concentration of a high molecular weight protein (~ 110 kd). In contrast, Mg2+ led to the total absence of the protein of lowest molecular weight (~7 kd) and increased concentration of a ~36 kd protein. CONCLUSION: These results suggest that elevation of some metal ions in the brain induces protein aggregation with the nature of the aggregation being highly ion dependent. The results also point toward major differences between the histopathological effect of Al3+ and other ions.

OBJETIVO: La enfermedad de Alzheimer y la enfermedad de Parkinson son dos de los varios trastornos neurodegenerativos que afectan al anciano. Aunque su etiologia sigue siendo incierta, los estudios sugieren que el aumento de los iones de aluminio, influyen directamente sobre el desarrollo de las anormalidades histológicas asociadas normalmente con estas enfermedades. Otras investigaciones sugieren que la disfunción de las mitocondrias, inducida por iones metálicos, pudiera ser un factor critico. MÉTODOS: Este estudio evalúa el impacto del aumento de los iones de aluminio (Al3+), los iones férricos (Fe3+), y los iones de calcio (Ca2+) y magnesio (Mg2+) sobre la histologia del cerebro y la composición proteica de las mitocondrias del cerebro. Un número de conejos recibieron inyecciones intracerebrales de soluciones al 1.4% de soluciones de cloruro de aluminio (AlCl3), cloruro ferroso (FeCl3), cloruro de calcio (CaCl2), o cloruro de magnesio (MgCl2), y fueron sacrificados después de 10 días. RESULTADOS: El análisis histológico reveló que el Al3+ indujo una degeneración neurofibrilar dentro del mesencéfalo y la médula, Sin embargo, esto no ocurrió con los otros iones. Alternativamente, la técnica de electroforesis SDS-PAGE reveló que los iones Fe3+, Ca2+ y Mg2+, a diferencia del ión Al3+, inducían alteraciones de la distribución de las proteínas mitocondriales cerebrales. Tanto el Fe3+ como el Ca2+ desencadenaron una disminución de la concentración de tres proteínas de bajo peso molecular (~7-14 kd) pero Ca2+ precipitó su ausencia total. Ambos iones condujeron a un aumento de una proteína de peso molecular alto (~ 110 kd). En cambio, Mg2+ llevó a la ausencia total de la proteína de más bajo peso molecular (~7 kd) y al aumento de la concentración de una proteína de ~36 kd. CONCLUSIÓN: Estos resultados parecen sugerir que la elevación de algunos iones de metal en el cerebro induce la agregación de la proteína, siendo la naturaleza de la agregación altamente dependiente de los iones. Los resultados también apuntan a grandes diferencias entre el efecto histopatológico del Al3+ y otros iones.

Insights into Alzheimer disease pathogenesis from studies in transgenic animal models

Alzheimer disease is the most common cause of dementia among the elderly, accounting for ~60-70 percent of all cases of dementia. The neuropathological hallmarks of Alzheimer disease are senile plaques (mainly containing p-amyloid peptide derived from amyloid precursor protein) and neurofibrillary tangles (containing hyperphosphorylated Tau protein), along with neuronal loss. At present there is no effective treatment for Alzheimer disease. Given the prevalence and poor prognosis of the disease, the development of animal models has been a research priority to understand pathogenic mechanisms and to test therapeutic strategies. Most cases of Alzheimer disease occur sporadically in people over 65 years old, and are not genetically inherited. Roughly 5 percent of patients with Alzheimer disease have familial Alzheimer disease-that is, related to a genetic predisposition, including mutations in the amyloid precursor protein, presenilin 1, and presenilin 2 genes. The discovery of genes for familial Alzheimer disease has allowed transgenic models to be generated through the overexpression of the amyloid precursor protein and/or presenilins harboring one or several mutations found in familial Alzheimer disease. Although none of these models fully replicates the human disease, they have provided valuable insights into disease mechanisms as well as opportunities to test therapeutic approaches. This review describes the main transgenic mouse models of Alzheimer disease which have been adopted in Alzheimer disease research, and discusses the insights into Alzheimer disease pathogenesis from studies in such models. In summary, the Alzheimer disease mouse models have been the key to understanding the roles of soluble b-amyloid oligomers in disease pathogenesis, as well as of the relationship between p-amyloid and Tau pathologies.

The Clinical use of quantitative EEG in cognitive disorders / A utilização clínica do EEG quantitativo nos transtornos cognitivos

Abstract: The primary diagnosis of most cognitive disorders is clinically based, but the EEG plays a role in evaluating, classifying and following some of these disorders. There is an ongoing debate over routine use of qEEG. Although many findings regarding the clinical use of quantitative EEG are awaiting validation by independent investigators while confirmatory clinical follow-up studies are also needed, qEEG can be cautiously used by a skilled neurophysiologist in cognitive dysfunctions to improve the analysis of background activity, slow/fast focal activity, subtle asymmetries, spikes and waves, as well as in longitudinal follow-ups.

Resumo: O uso clínico do EEG Quantitativo nas doenças cognitivas. O diagnóstico das doenças cognitivas geralmente é clínico mas o EEG é importante como exame auxiliar na avaliação, diagnóstico e classificação de algumas delas. O debate atual refere-se ao uso clínico do EEGq. Embora muitos achados no EEGq ainda aguardem validação, o EEGq pode ser usado cautelosamente em situações específicas e por um neurofisiologista experiente. Nas doenças cognitivas ele pode contribuir na análise da atividade de base, em atividades focais lentas ou rápidas, assimetrias sutís, pontas e ondas e no acompanhamento longitudinal dos pacientes.

The clinical use of quantitative EEG in cognitive disorders.

The primary diagnosis of most cognitive disorders is clinically based, but the EEG plays a role in evaluating, classifying and following some of these disorders. There is an ongoing debate over routine use of qEEG. Although many findings regarding the clinical use of quantitative EEG are awaiting validation by independent investigators while confirmatory clinical follow-up studies are also needed, qEEG can be cautiously used by a skilled neurophysiologist in cognitive dysfunctions to improve the analysis of background activity, slow/fast focal activity, subtle asymmetries, spikes and waves, as well as in longitudinal follow-ups.

O uso clínico do EEG Quantitativo nas doenças cognitivas. O diagnóstico das doenças cognitivas geralmente é clínico mas o EEG é importante como exame auxiliar na avaliação, diagnóstico e classificação de algumas delas. O debate atual refere-se ao uso clínico do EEGq. Embora muitos achados no EEGq ainda aguardem validação, o EEGq pode ser usado cautelosamente em situações específicas e por um neurofisiologista experiente. Nas doenças cognitivas ele pode contribuir na análise da atividade de base, em atividades focais lentas ou rápidas, assimetrias sutís, pontas e ondas e no acompanhamento longitudinal dos pacientes.