Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Corticobasal syndrome is characterized by cortical dysfunction and L-dopa-unresponsive Parkinsonism, with asymmetrical onset of clinical presentation and evidence of atrophy and/or hypometabolism at neuroimaging. Recently, the heterogeneous pathologic substrate of corticobasal syndrome has been further expanded to include cases with pathologic diagnosis of frontotemporal lobar degeneration with ubiquitin/TDP-43 (TAR DNA binding protein 43)-positive inclusions associated with progranulin (PGRN) mutations. We report a family in which several individuals have been affected with a dementia/movement disorder phenotype. The proband presented at age 45 with spontaneous left arm levitation, ideational apraxia, asymmetric parkinsonism, and dystonia. Subsequently, he developed limb-kinetic apraxia, left-side hemineglect, memory loss, and executive dysfunction. Magnetic resonance imaging and [F]fluorodeoxyglucose-positron emission tomography studies revealed severe cerebral cortical atrophy and hypometabolism, which were significantly more pronounced in the parietal lobes (right > left). Neuropathologic examination displayed the highest degree of degeneration and ubiquitin/TDP-43 pathology in the proband's parietal areas. Genetic analysis revealed the presence of the c.26C>A PGRN mutation in 1 allele. This mutation has been reported in association with hereditary-dysphasic-disinhibition-dementia, Alzheimer-like dementia, progressive supranuclear palsy, and primary progressive aphasia. The peculiar findings observed in this patient indicate that the parietal lobe may represent the most vulnerable anatomical area in some of the PGRN-associated frontotemporal lobar degeneration with ubiquitin/TDP-43-positive inclusion cases.
 ...
PMID:Corticobasal syndrome associated with the A9D Progranulin mutation. 1791 83

Bipedal locomotion and fine motility of hand and larynx of humans introduced musculoskeletal adaptations, new pyramidal, corticostriatal, corticobulbar, nigrostriatal, and cerebellar pathways and expansions of prefrontal, cingular, parieto-temporal and occipital cortices with derived new brain capabilities. All selectively degenerate in aged homo sapiens following 16 syndromic presentations: (1) Parkinsonism: nigrostriatal control for fast automatic movements of hand, larynx, bipedal posture and gait ("simian gait and hand"). (2) Frontal (highest level) gait disorders (lower body parkinsonism, gait apraxia, retropulsion): prefrontostriatal executive control of bipedal locomotion. (3) ataxia: new synergistic coordination of bipedal gait and fine motility. (4) Dyskinesias (chorea, dystonia, tremor...): intrusions of simian basal ganglia motor subroutines. (5) motoneuron diseases: new proximo-distal and bulbar motoneurones, preserving older ones (oculomotor, abdominal...). (6) Archaic reflexes: prefrontal disinhibition of old mother/tree-climbing-oriented reflexes (sucking, grasping, Babinski/triple retraction, gegenhalten), group alarms (laughter, crying, yawning, grunting...) or grooming (tremor=scratching). (7) Dysautonomia: contextual regulation (orthostatism...). (8) REM sleep disorders of new cortical functions. (9) Corticobasal syndrome: melokinetic control of hand prehension-manipulation and language (retrocession to simian patterns). (10) Frontal/temporal lobe degeneration: medial-orbitofrontal behavioural variant: self monitoring of internal needs and social context: apathy, loss of personal hygiene, stereotypia, disinhibition, loss of concern for consequences of acts, social rules, danger and empathy; dorsolateral executive variant: inadequacy to the context of action (goal, environmental changes...); progressive non-fluent aphasia: executive and praxic processing of speech; temporal variant: abstract concepts for speech, gestures and vision (semantic dementia, progressive nonfluent aphasia) (11) Temporomesial-limbic-paralimbic-associative cortical dementias (Alzheimer's disease, Lewy body, progressive amnesia): processing of explicit cognition: amnesic syndrome, processing of hand, larynx and eye: disorientation, ideomotor apraxia, agnosia, visuospatial processing, transcortical aphasia. (12) Focal posterior atrophy (Benson, progressive apraxia): visuomotor processing of what and where. (13) Macular degeneration: retinal "spot" for explicit symbols. (14) "Psychiatric syndromes": metacognition, self monitoring and regulation of hierarchical processing of metacognition: hallucinations, delusions, magic and mystic logic, delusions, confabulations; drive: impulsivity, obsessive-compulsive disorders, mental automatisms; social interactions: theory of mind, autism, Asperger. (15) Mood disorders: control on emotions: anxio-depressive and bipolar disorders, moria, emotional lability. (16) Musculoskeletal: inclusion body myositis: muscles for bipedal gait and fine motility. Paget's disease: bones for bipedal gait and cranium. Understanding of the genetic mechanisms underlying the evolution of these recent human brain regions and paleoneurology my be the key to the focal, asymmetrical or systemic character of neurodegeneration, the pathologic heterogeneity/overlap of syndromic presentations associating gait, hand, language, cognition, mood and behaviour disorders.
 ...
PMID:Paleoneurology: neurodegenerative diseases are age-related diseases of specific brain regions recently developed by Homo sapiens. 1870 90

Frontotemporal degeneration (FTD), formerly known as Pick's disease has become recognized as a distinct and relatively common entity encompassing behavioural (bvFTD language (PPA) and extrapyramidal (CBD/PSP) presentations. Further clinical subdivisions such as semantic dementia(SD), and pathological subtypes such as mesial temporal sclerosis increase the complexity of diagnosis.The relatively younger age of onset, the typical presentations of syndromes and focal asymmetrical frontotemporal atrophy on imaging allows experienced clinicians to make the diagnosis confidently as long as the overlap between the syndromes is recognized. There is also an overlap with ALS pathologically and clinically. The underlying histology in FTD/Pick complex is ubiquitin positive tau and synuclein negative neuronal inclusions (FTLD-U) in more than half of autopsies and tau positive CBD/PSP/ Pick bodies (FTLD-T) in the rest. The clinical syndromes of bvFTD and SD are likely associated with FTLD-U and PPA/CBDS/PSP with FTLD-T, but there is too much overlap to predict the pathology from the clinical syndromes reliably. The ubiquitin-tau pathological dichotomy is best considered under the Pick complex umbrella to allow for the significant overlap. So far trazodone in behavior and galantamine in aphasia had symptomatic benefit in small trials and SSRI-sand antipsychotics in uncontrolled reports were used as symptomatic therapies. Recent discoveries of tau and progranulin (in the ubiquitin-positive cases) mutations on chromosome 17 and other mutations on chromosome 3 and 9 in the high incidence of autosomal dominant families and a common protein abnormality, the TDP-43 in FTLD-U and ALS are likely to be important in finding therapeutic targets.
 ...
PMID:Clinical features and diagnosis of frontotemporal dementia. 1918 72

Frontotemporal lobar degeneration is currently associated with three syndromic variants. Disorders of speech and language figure prominently in two of the three variants, and are associated with left-sided frontotemporal atrophy. The detailed characterization of these syndromes contrasts with the relative paucity of information relating to frontotemporal lobar degeneration primarily affecting the right cerebral hemisphere. The objective of this study was to identify the clinical profile associated with asymmetrical, predominantly right-sided, temporal lobe atrophy. Twenty patients with predominant right temporal lobe atrophy were identified on the basis of blinded visual assessment of the MRI scans. The severity of right temporal lobe atrophy was quantified using volumetric analysis of the whole temporal lobes, the amygdala and the hippocampus. Profiles of cognitive function, behavioural and personality changes were obtained on each patient. The pattern of atrophy and the clinical features were compared with those observed in a group of patients with semantic dementia and predominant left-sided temporal lobe atrophy. The mean right temporal lobe volume in the right temporal lobe atrophy group was reduced by 37%, with the mean left temporal lobe volume reduced by 19%. There was marked atrophy of the right hippocampus and right amygdala, with mean volumes reduced by 41 and 51%, respectively (left hippocampus and amygdala volumes were reduced by 18 and 33%, respectively). The most prominent cognitive deficits were impairment of episodic memory and getting lost. Prosopagnosia was a symptom in right temporal lobe atrophy patients. These patients also exhibited a variety of behavioural symptoms including social disinhibition, depression and aggressive behaviour. Nearly all behavioural disorders were more prevalent in the right temporal lobe atrophy patient group than the semantic dementia group. Symptoms particular to the right temporal lobe atrophy patient group included hyper-religiosity, visual hallucinations and cross-modal sensory experiences. The combination of clinical features associated with predominant right temporal lobe atrophy differs significantly from those associated with the other syndromes associated with focal degeneration of the frontal and temporal lobes and it is, therefore, proposed that this right temporal variant should be considered a separate syndromic variant of frontotemporal lobar degeneration.
 ...
PMID:The clinical profile of right temporal lobe atrophy. 1929 6

The aspects of various neurodegenerative diseases can be observed overlapping with each other during autopsy. Corticobasal degeneration (CBD) is a rare neurodegenerative disease, whereas Alzheimer disease (AD) is the most common cause of dementia. In this article, we present the combination of CBD and AD in an autopsy case. The patient, an 82-year-old right-handed woman developed asymmetrical parkinsonism, visuospatial dysfunction and memory loss, as well as subsequent non-influent aphasia over the past 10 years. The autopsy revealed characteristic CBD-related pathology, ballooned neurons, globose tangles and astrocytic plaques, mainly in the frontal cortex and basal ganglia. The Alzheimer-related pathology was also present concomitantly. Senile plagues deposited diffusively throughout the hippocampus and neocortices. Neurofibrillary tangles (NFTs) were more confined to the hippocampus. The autopsy demonstrated pathological overlap of CBD and AD, which therefore explained the clinical early development of dementia and parkinsonism. We should suspect the concurrence of various neurodegenerative disorders in any case with atypical or complex clinical manifestations. Tau pathology is a prominent feature in both CBD and AD. Such a combination would be a clue for the pathogenesis of various tauopathies.
 ...
PMID:The overlap of corticobasal degeneration and Alzheimer changes: an autopsy case. 1932 89

Frontotemporal lobar degeneration (FTLD) has been clinically categorized into 3 subtypes: frontotemporal dementia, semantic dementia, and progressive nonfluent aphasia. The histological subtypes of FTLD are Pick disease, corticobasal degeneration, dementia with grain, dementia with ubiquitin-positive tau-negative inclusions, and amyotrophic lateral sclerosis with dementia. In this paper, I briefly describe the magnetic resonance imaging (MRI) findings in Pick disease, progressive nonfluent aphasia, semantic dementia, and dementia with grain. In Pick disease, so-called knife-blade atrophy is seen in the frontal and temporal lobes at a relatively early stage of the disease. In progressive nonfluent aphasia atrophy is seen in the upper part of the left frontal lobe. Marked atrophy in the left temporal pole is observed in patients with semantic dementia, and asymmetrical atrophy around the ambient gyri is detected in patients who have dementia with grains. Although such focal atrophy can be observed on routine MRI, it is more easily detected on voxel-based morphometry and voxel-based specific regional analysis system for Alzheimer disease (VSRAD).
 ...
PMID:[Magnetic resonance imaging for frontotemporal lobar degeneration]. 1993 83

Frontotemporal lobar degeneration (FTLD) refers to a clinically, pathologically, and genetically heterogeneous group of dementias that arises from the degeneration of the frontal and temporal lobes. Mutations in the progranulin gene (GRN) are a major cause of FTLD with TDP-43 inclusions. Herein, we describe the clinical, neuropathological, and genetic findings in a case of autosomal dominant behavioral variant of frontotemporal dementia (bvFTD) with asymmetrical parkinsonism and prominent visuospatial deficits that carries a novel GRN mutation. This case highlights important clinical characteristics that seem to be common in FTLD GRN-associated patients, such as asymmetrical parkinsonism and parietal symptoms, and that are correlated to the pathological involvement of striatum (rather than substantia nigra in our case) and parietal lobe. We also emphasize that plasma progranulin level can be useful to infer about the pathogenicity of new GRN mutations.
 ...
PMID:Clinical, neuropathological, and genetic characteristics of the novel IVS9+1delG GRN mutation in a patient with frontotemporal dementia. 2236 70

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder which presents with either behavioral or language impairment. The two language syndromes are known as progressive nonfluent aphasia (PNFA) and semantic dementia (SEMD). While cross-sectional imaging patterns of brain atrophy are well-described in FTLD, fewer studies have investigated longitudinal imaging changes. We measured longitudinal hemispheric and lobar atrophy rates using serial MRI in a cohort of 18 patients with PNFA and 17 patients with SEMD as well as 14 cognitively-normal control subjects. We subsequently calculated sample size estimates for clinical trials. Rates of left hemisphere atrophy were greater than rates of right hemisphere atrophy in both PNFA and SEMD with no significant differences between the groups. The disease groups showed asymmetrical atrophy (more severe on the left) at baseline with significantly increasing asymmetry over time. Within a hemisphere, the fastest rate of atrophy varied between lobes: in SEMD temporal > frontal > parietal > occipital, while in PNFA frontal > temporal/parietal > occipital. In SEMD, using temporal lobe measures of atrophy in clinical trials would provide the lowest sample sizes necessary, while in PNFA left hemisphere atrophy measures provided the lowest sample size. These patterns provide information about disease evolution in the FTLD language variants that is of both clinical and neurobiological relevance.
 ...
PMID:Rates of hemispheric and lobar atrophy in the language variants of frontotemporal lobar degeneration. 2240 42

The cardinal symptoms of Parkinson disease (PD) are asymmetrical bradykinesia, rigidity, resting tremor and postural instability. However, the presence and spectrum of, and disability caused by, nonmotor symptoms (NMS) are being increasingly recognized. NMS include dementia, psychosis, depression and apathy, and are a major source of disability in later stages of PD, in association with axial symptoms that are resistant to levodopa therapy. The model of clinical progression of PD should, therefore, incorporate NMS, instead of being restricted to motor signs and levodopa-induced motor complications. Patients with disabling motor complications are classified as having advanced PD, which has been thought to represent the ultimate stage of disease. However, deep brain stimulation to treat motor complications has dramatically changed this scenario, with implications for the definition of advanced-stage disease. As treatment improves and survival times increase, patients are increasingly progressing to a later phase of disease in which they are highly dependent on caregivers, and disability is dominated by motor symptoms and NMS that are resistant to levodopa. In this article, we review the changing landscape of the later stages of PD, and propose a definition of late-stage PD to designate patients who have progressed beyond the advanced stage.
 ...
PMID:Late-stage Parkinson disease. 2277 51

Marchiafava-Bignami disease (MBD) is a rare alcohol-associated disorder. Clinical features include not only disturbed consciousness, dysarthria, tetraparesis, astasia-abasia, and symptoms of interhemispheric disconnection as initial symptoms but also cognitive deficits as clinical outcomes. The clinical significance of cerebral microhemorrhage (CMH) has been recognized in patients with cognitive deficits; however, the presence of CMH in patients with MBD has not been emphasized. The aim of the present study was to clarify the relationship between CMH and MBD. For this purpose, we report four patients with MBD, who showed asymmetrical hypointense areas in multiple cortico-subcortical regions on susceptibility-weighted imaging (SWI). All cases had a history of chronic alcohol abuse and symmetrical lesions in the entire corpus callosum. These patients' clinical symptoms included not only coma, dysarthria, and astasia-abasia as initial symptoms but also dementia as a clinical outcome. SWI showed asymmetrical hypointense areas in the multiple cortico-subcortical regions, indicating the presence of CMH. Compared with patients with normal cognitive function, demented patients showed higher severity of CMH. Our report would indicate that CMH is an important factor indicating the severity of dementia in patients with MBD.
 ...
PMID:Cerebral microhemorrhage in Marchiafava-Bignami disease detected by susceptibility-weighted imaging. 2277 68


<< Previous 1 2 3 4 5 6 Next >>