Neurology (E-Cronicon)最新文献

Dopaminergic dysfunction in reward circuitry is well-documented as a contributor to addictive behaviors. Evidence indicates that changes in synchronous neural activity between brain regions mediating reward and cognitive functions may significantly contribute to substance-related disorders. In this commentary we highlight findings showing that the pro-dopaminergic nutraceutical (KB220) enhances functional connectivity between reward and cognitive brain areas in both animal and human studies. Animal studies demonstrate that KB220 activates important brain reward-related regions, including the nucleus accumbens, anterior cingulate gyrus, anterior thalamic nuclei, hippocampus, and prelimbic and infralimbic loci. Kb220 induced significant functional connectivity, enhanced neuroplasticity, and improved dopaminergic functionality within the brain reward circuitry with effects localized to these regions rather than broader distributed across the brain. In abstinent heroin-dependent individuals, acute KB220 administration significantly induced BOLD activation in caudate-accumbens dopaminergic pathways relative to placebo. Furthermore, data from 36 clinical trials and preclinical studies encompassing over 1,000 subjects, demonstrate that KB220 supports "dopamine homeostasis" across various reward deficiency behaviors. Clinical outcomes and quantitative electroencephalogy (qEEG) results underscore KB220's potential anti-craving/anti-relapse effects in addiction and other psychiatric disorders through direct or indirect dopaminergic modulation. Based on a review of the existing knowledge and further intensive investigation, we propose that instead of relying on mono-pharmaceutical approaches, the scientific community should endorse multi-loci dopaminergic restoration of reward brain circuitry as a fundamental paradigm for addressing mental illness.

Many US states now embrace the medical and recreational use of Cannabis. Changes in the laws have heightened interest and encouraged research into both cannabinoid products and the potential harms of Cannabis use, addiction and intoxication. The major active ingredient of Cannabis sativa (marijuana), Δ⁹-tetrahydrocannabinol (THC) and it powerfully stimulates the type-1 cannabinoid (CB₁) receptor. When used in the form of the plant marijuana, because of the many compounds that exist in the plant form they could inhibit the activity of the CB₁ receptor thereby reducing many of the effects of THC. While this mechanism seems correct, in our opinion, Vallee., et al. incorrectly suggest that blocking CB₁ receptors could open unforeseen approaches to the treatment of cannabis intoxication and addiction. We caution the scientific community that, other CB₁ receptor blockers, such as, Rimonabant (SR141718) have been pulled off the market in Europe. In addition, CB₁ receptor blockers were rejected by the FDA due to mood changes including suicide ideation. We argue that one issue facing the scientific community, has to do with the increasing legalization of Cannabis products in many states across America. We are in favor of some reform in terms of either decriminalization or restrictive legalization especially in control of legal limits of THC. Like other psychoactive compounds at high doses, it is our hypothesis that chronic use of these drugs including high THC content in its various forms (wax, smoke or vapor) resulting in brain reward dysfunction induces an imbalance of neurotransmission and subsequent hypodopaminergia and lead to aberrant substance and non-substance (behavioral) addictions. It is further proposed that in order to overcome THC and even other psychoactive drugs of abuse induced anhedonia the coupling of genetic risk testing and pro dopamine regulation is warranted.

Introduction: The gut microbiome appears to be predictive of Parkinson's disease (PD) with constipation. Chronic constipation frequently manifests prior to motor symptoms and impairs quality of life. An osteopathic manipulative medicine (OMM) sequence used physical exam assessment and manual treatment of neuromusculoskeletal dysfunctions pertinent to constipation in PD for this prospective ABA-design study, IRB-NYITBHS1065. The effects of 4 weekly treatments on the gut microbiome among men and women over 40 years old with chronic constipation and PD were investigated. Severity of PD was rated with the Movement Disorders Society-Unified PD rating scale (UPDRS) in six subjects with constipation. Also, the Bristol stool scale and questionnaires validated for constipation were administered for diagnosis, symptom severity, and quality of life during a 4-week control-period (A), 4-weekly OMM-treatments (B), and 2-weeks no-intervention (A). Biweekly stool samples were assessed for normalized microbiota abundance.

Results: The mean Bristol rating improved from type 2 (± 1) Pre-OMM to 3 (± 1; p = .167; d = 0.677) Post-OMM. Mean constipation severity significantly decreased (p = .010; d = 1.508) Post-OMM. Mean quality of life significantly improved (p = .041; d = 1.072) Post-OMM. The Pre-OMM mean number of families within the phylum Firmicutes decreased by 3 (p = .043; d = 1.177) Post-OMM. There were significant changes in the normalized abundance of phyla Actinobacteria (p = .040; d = 0.845) and Verrucomicrobia (p = .024; d = 0.675) as well as in genus Roseburia (p = .033; d = 1.109), Intestinimonas (p = .035; d = 0.627) and Anaerotruncus (p = .004) Post-OMM.

Conclusion: The gut microbiome shifted among individuals with constipation and PD after four weekly treatments with the OMM-sequence. Changes in the gut microbiome Post-OMM were associated with UPDRS results and constipation measures. Clinical trials and studies to develop the gut microbiome into a validated biomarker for PD are necessary to understand the impact of OMM in patients with PD and constipation.

Objectives: Veterans and patients with epilepsy are at higher risk of suicide than the general population. Some studies suggest that antiepileptic drugs (AEDs) further increase the risk of suicide. The nature of the relationship between suicidality and epilepsy treatment needs clarification. We examined this relationship in a cohort of veterans with seizures.

Methods: We performed a retrospective chart analysis of patients at the Philadelphia VA Medical Center with a diagnosis of seizure disorder between January 2000 and April 2007. Patients with suicidal ideation and/or suicidal behaviors were analyzed with respect to the following risk factors: age, history of traumatic brain injury (TBI), substance abuse and AED prescription.

Results: 526 charts were reviewed, 385 of which met inclusion criteria. Patients with substance abuse were more likely to have suicidal ideation (adjusted odds ratio 3.37, 95% CI 1.84 -6.18). Risk decreased with age (adjusted odds ratio 0.94, 95% CI 0.92 - 0.97 for each year). There was no statistically significant relationship between suicidality and AED use or history of TBI.

Conclusion: In our population, AEDs were not associated with increased risk of suicidality, whereas substance abuse was associated with a substantial risk increase. The interactions among seizures, suicidality, substance abuse and other neuropsychiatric diseases are complex. Large-scale studies in patients with seizures are needed to understand the impact of individual drugs and other contributing factors. Providers should be cautious not to withhold potentially beneficial treatment, however patients with risk factors such as history of substance abuse should be followed closely after AED initiation or adjustment.

Neurodegenerative diseases demonstrate the progressive decline of brain functions resulting in a significant deterioration in the quality of patient's life. With increasing life expectancy, there has been a significant increase in the incidence of these diseases. Neurodegenerative diseases like Alzheimer's, Parkinson's, and Amyotrophic lateral sclerosis are devastating and afflicts a large world population. Eye, given the similar neural and vascular similarity to the brain, demonstrates many pathological hallmarks of some of these neurological diseases. Moreover, these diseases create an economic and social burden to society. Despite tremendous efforts made in the drug discovery, there is no cure for these fatal diseases. Thus, there is an unmet need to understand cellular and molecular pathophysiology of these diseases. All these diseases demonstrate damage to a large number of seemingly disparate cellular processes and functions such as Ca⁺² homeostasis, lipid metabolism, axonal transport, unfolded protein response, autophagy and inflammatory responses. Mitochondria are closely associated with Endoplasmic reticulum (ER) and ER-mitochondrial cross-talk regulates many of these cellular processes and functions damaged in neurodegenerative and eye diseases. Several studies have implicated the disruption of ER-mitochondria contacts in these diseases. This review is aimed at understanding and summarizing the role of ER-mitochondria interacting proteins in major neurodegenerative and eye diseases studied so far.

Objectives: The Hoffman-reflex (H-reflex) is an electrophysiological technique used to evaluate the excitability of the monosynaptic spinal reflex arc. In individuals with upper motor neuron lesions who show elevated spinal excitability, a depression of spinal excitability may indicate adaptive spinal plasticity. Downslope walking (DSW), an exercise intervention comprising repetitive eccentric muscle activity, has been shown to induce depression of soleus H-reflex amplitudes while seated, however, the dose-response time-course of H-reflex modulation during DSW has not been characterized. The objectives of this study were twofold: (1) to evaluate DSW-induced soleus H-reflex depression in the standing posture and during walking, and (2) to investigate the effect of walking duration (20 minutes and 40 minutes) of DSW (-15% decline) on soleus H-reflexes, (with level walking (LW) as a control intervention).

Methods: Soleus H-reflexes were collected Pre, Post-20 minutes, and Post-40 minutes of walking in the standing position; and H-reflexes were also measured at 4 different time points during the terminal stance phase of walking.

Results: Our results showed that soleus H-reflexes evaluated in standing showed a greater % depression after DSW compared to LW, with a statistical trend for greater depression with longer durations (40-minutes). H-reflexes measured during walking showed greater depression after 40 minutes of walking compared to 20- or 30-minutes for both DSW and LW.

Conclusions: Longer duration treadmill walking (40-minutes) may induce a greater acute depressive effect on soleus H-reflex excitability compared to shorter durations (20-minutes) of treadmill walking. Future work will investigate the potential for DSW as a gait training intervention in people with upper motor neuron lesions such as multiple sclerosis and stroke.

Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are stigmatizing illnesses characterized by cognitive difficulties, post-exertional malaise, unrefreshing sleep, and other symptoms. Patients are often incapacitated and stigmatized as having a psychological disorder. The Chronic Fatigue Attitudes Test (CAT) assesses stigmatizing views toward individuals with Chronic Fatigue Syndrome, however, there is little research examining factors that may account for variation in stigmatizing attitudes toward this group. We examined CAT scores among college age research volunteers (N = 90), hypothesizing that exposure to information about ME and CFS as a result of volunteering on a ME and CFS-related research project would be associated with less stigmatizing attitudes compared to volunteers on unrelated projects. Findings indicated that ME and CFS research volunteers expressed less stigmatizing attitudes. Educational efforts aiming to disseminate accurate information about ME and CFS may mitigate stigma and the experience of stigma among individuals with ME and CFS.

The Institute of Medicine (IOM) recently developed clinical criteria for chronic fatigue syndrome (CFS). There might be additional criteria that could select a more homogenous and impaired group of patients, particularly those with pain. The current study focused on criteria which involved meeting the four IOM criteria, excluding medical and psychiatric co-morbidities, along with having fibromyalgia (FM). Findings indicated that those meeting the IOM clinical criteria plus FM were more impaired on a wide variety of symptoms and functional areas than those meeting on the IOM criteria or those with just 6 months of fatigue. The implications of using such research criteria are discussed.

Few studies have explored the rate of cognitive decline and caregiver burden within the context of a specialized memory clinic. When this was done, the focus was largely on functional decline related to Alzheimer's disease (AD). Our goal was to compare the longitudinal decline of AD patients to those with Vascular Dementia (VaD) on Mini-Mental State Examination (MMSE). We further explored the differential impact on caregiver burden. We retrospectively studied 237 charts from patients seen at our Memory Clinic between 2006 and 2012. The data was collected over 17 years. Cohorts were formed by excluding conditions other than AD and VaD, and including patients who had been assessed at least twice with the MMSE (AD: n = 83; mean age: 67.7 yo; VaD: n = 32; mean age: 73.3yo). A small group of 36 caregivers was surveyed by phone to explore caregiver burden. Results indicated that the natural history of MMSE changes in AD patients differed significantly from that of patients with VaD (F = 10.41, p<0.0014), with AD patients showing more cognitive decline over time. Sadness, stress/anxiety, fatigue, and sleep disorders were reported as the main preoccupations by caregivers and its impact was rated as 'severe' in 50% of cases. Altogether, this study provides further insight into the natural history of cognitive decline in AD and VaD. Future studies should explore the progression of dementing disorders in larger cohorts using prospective methodological designs.