Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018991 (hemiplegia)
 3,997 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rapid-onset dystonia-parkinsonism (RDP) is a movement disorder associated with mutations in the ATP1A3 gene. Signs and symptoms of RDP commonly occur in adolescence or early adulthood and can be triggered by physical or psychological stress. Mutations in ATP1A3 are also associated with alternating hemiplegia of childhood (AHC). The neuropathologic substrate of these conditions is unknown. The central nervous system of four siblings, three affected by RDP and one asymptomatic, all carrying the I758S mutation in the ATP1A3 gene, was analyzed. This neuropathologic study is the first carried out in ATP1A3 mutation carriers, whether affected by RDP or AHC. Symptoms began in the third decade of life for two subjects and in the fifth for another. The present investigation aimed at identifying, in mutation carriers, anatomical areas potentially affected and contributing to RDP pathogenesis. Comorbid conditions, including cerebrovascular disease and Alzheimer disease, were evident in all subjects. We evaluated areas that may be relevant to RDP separately from those affected by the comorbid conditions. Anatomical areas identified as potential targets of I758S mutation were globus pallidus, subthalamic nucleus, red nucleus, inferior olivary nucleus, cerebellar Purkinje and granule cell layers, and dentate nucleus. Involvement of subcortical white matter tracts was also evident. Furthermore, in the spinal cord, a loss of dorsal column fibers was noted. This study has identified RDP-associated pathology in neuronal populations, which are part of complex motor and sensory loops. Their involvement would cause an interruption of cerebral and cerebellar connections which are essential for maintenance of motor control.
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PMID:Rapid-onset dystonia-parkinsonism associated with the I758S mutation of the ATP1A3 gene: a neuropathologic and neuroanatomical study of four siblings. 2480 25

Stroke commonly leads to adult disability and death worldwide. Its major symptoms are spastic hemiplegia and discordant motion, consequent to neuronal cell death induced by brain vessel occlusion. Acetylcholinesterase (AChE) is upregulated and allied with inflammation and apoptosis after stroke. Recent studies suggest that AChE inhibition ameliorates ischemia-reperfusion injury and has neuroprotective properties. (-)-Phenserine, a reversible AChE inhibitor, has a broad range of actions independent of its AChE properties, including neuroprotective ones. However, its protective effects and detailed mechanism of action in the rat middle cerebral artery occlusion model (MCAO) remain to be elucidated. This study investigated the therapeutic effects of (-)-phenserine for stroke in the rat focal cerebral ischemia model and oxygen-glucose deprivation/reperfusion (OGD/RP) damage model in SH-SY5Y neuronal cultures. (-)-Phenserine mitigated OGD/PR-induced SH-SY5Y cell death, providing an inverted U-shaped dose-response relationship between concentration and survival. In MCAO challenged rats, (-)-phenserine reduced infarction volume, cell death and improved body asymmetry, a behavioral measure of stoke impact. In both cellular and animal studies, (-)-phenserine elevated brain-derived neurotrophic factor (BDNF) and B-cell lymphoma 2 (Bcl-2) levels, and decreased activated-caspase 3, amyloid precursor protein (APP) and glial fibrillary acidic protein (GFAP) expression, potentially mediated through the ERK-1/2 signaling pathway. These actions mitigated neuronal apoptosis in the stroke penumbra, and decreased matrix metallopeptidase-9 (MMP-9) expression. In synopsis, (-)-phenserine significantly reduced neuronal damage induced by ischemia/reperfusion injury in a rat model of MCAO and cellular model of OGD/RP, demonstrating that its anti-apoptotic/neuroprotective/neurotrophic cholinergic and non-cholinergic properties warrant further evaluation in conditions of brain injury.
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PMID:(-)-Phenserine inhibits neuronal apoptosis following ischemia/reperfusion injury. 2896 51

There is now general agreement that lack of insight is not merely a fundamental aspect of delusions and hallucinations, or just a symptom of psychotic disorders but rather a multi-dimensional construct. Several different components of insight have been proposed and empirically examined during the last three decades, such as the ability to recognize that one has a mental illness, the capacity to relabel unusual mental events as pathological, the specific attribution of one's symptoms to having a mental illness, awareness of illness' consequences, and compliance with treatment.1 Insight impairment is an important prognostic factor in schizophrenia, impacting negatively on medication adherence, treatment outcome, and social functioning.2 Although largely investigated in schizophrenia and other psychoses, insight impairments are observed in many, if not all, mental disorders. Varying levels of awareness of mental illness and/or of specific symptoms are expected in patients with bipolar disorders, Alzheimer disease and other neurocognitive disorders, obsessive-compulsive (OCD) and related disorders.1,3 While in DSM-5 an "insight" specifier was incorporated for OCD, body dysmorphic and hoarding disorder, patients' insight has been found ranging from good to absent in other disorders, such as depressive disorders,4 eating disorders,5 and even specific6 and social7 phobias. Moreover, impaired insight is a common reason that many people with clinical depression or anxiety disorders never seek appropriate treatment and most of the people with addictions and personality disorders fail to recognize and address their problems even when the consequences are devastating: personal suffering, broken relationships, and physical health problems. Depending on the disorder and reflecting different conceptual approaches, many different terms are used to describe lack of insight, such as poor self-awareness, denial, anosognosia (mainly in neurological deficits, e.g. hemiplegia), ego-syntonic symptoms, or even self-deception. At any rate, as an aspect of self-knowledge, insight has psychological (defense mechanisms, coping strategies), social and cultural facets. On the other hand, the attitudes and behaviours towards one's illness are products of inference processes and therefore can be influenced by cognitive dysfunctions. Previous research in schizophrenia showed correlations between neurocognitive functions and insight measures but the strength of this association is rather weak.8 Social cognition may be a crucial cognitive determinant of impaired insight in schizophrenia. The correct attitude toward morbid change in oneself relies on the capacity to reflect upon self from the perspective of the other (i.e., "to see ourselves as others see us"). This capacity is clearly linked to the ability to understand mental states (e.g., beliefs, knowledge, and intentions) of others, that is, theory of mind or mentalizing. Recent research has shown that mentalizing deficits may substantially contribute to insight impairment in schizophrenia.9 This effect could be further examined in the broader context of patient's failures in metacognition, i.e. the general ability to think about thinking, and their relationships with insight impairment in schizophrenia. Mentalizing and introspection are closely related developmentally and it is yet unclear which one is the primary ability: we are able to understand others and then apply this understanding to ourselves or we are able to reflect on ourselves and then apply this reflection to others. A recent line of research in schizophrenia is based on the distinction introduced by Beck et al10 between clinical insight (i.e., awareness of illness) and cognitive insight, which describes a metacognitive ability, specifically patients' flexibility towards their beliefs, judgements and experiences. The self-report Beck Cognitive Insight Scale (BCIS) examines two subcomponents: self-certainty, assessing overconfidence about being right (e.g. "I know better than anyone else what mycomponents: self-certainty, assessing overconfidence about being right (e.g. "I know better than anyone else what my problems are"), and self-reflectiveness, assessing willingness to accept external feedback and recognition of dysfunctionalreasoning style (e.g. "Some of the ideas I was certain were true turned out to be false"). Cognitive insight in thisform describes two related but distinct aspects of metacognition in patients with psychosis, differentially associated withclinical insight, symptoms, treatment outcomes, and functioning.11 Another method for assessment of similar metacognitiveskills also used in schizophrenia is a scale (Metacognition Assessment Scale - Abbreviated, MAS-A) that is administeredthrough a specific interview and examines the capacities of self-reflectivity, understanding of the other individuals'mental states, and using metacognitive knowledge to respond to psychosocial challenges. Lysaker and colleaguesfound recently that metacognitive deficits assessed with MAS-A predict impaired insight in schizophrenia independentof symptoms.12 It is questionable whether BCIS and other methods used so far to assess self-reflection in psychoses arevalid and useful for patients with non-psychotic disorders.11 However, the metacognitive conceptualization of insightmight contribute to a new research framework for insight impairments across mental disorders. According to this approach, poor insight is in part a failure of self-reflection, i.e. the process by which we synthesizeand comprehend ideas about ourselves. This may be due to general deficits in metacognitive abilities (self-reflectivity,mentalizing) or may represent limited, domain-specific, or transient dysfunctions in metacognitive processes. Insight hasto be thought of as a relational concept, that is insight into something: insight into illness, current syndrome, specificsymptoms, pathological personality traits, social difficulties etc.1,3 In an integrated model of insight across mental disorders,aspects of metacognition interacting with multiple other (clinical, neurocognitive, emotional, and social) factorsdetermine patient's ability to correctly process information into self-awareness. The identification of these factors andtheir interactions may be a fruitful field in the research of insight.
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PMID:Insight across mental disorders: A multifaceted metacognitive phenomenon. 3111 49