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)

We have established that the frequency of LRRK2 mutations in a series of 118 cases of familial Parkinson's disease is 5.1%. In the largest family with autosomal dominant, late-onset Parkinson's disease where affected subjects share a Y1699C missense mutation we provide a detailed clinical, pathological and imaging report. The phenotype in this large British kindred included asymmetrical, levodopa-responsive parkinsonism where unilateral leg tremor at onset and foot dystonia were prominent features. There was no significant abnormality of cognition but there was prominent behavioural disorder. We observed a lower age of onset in successive generations. Histopathology in one patient showed substantia nigra cell loss and Lewy body formation, with small numbers of cortical Lewy bodies. 18F-dopa positron emission tomography (PET) in another patient showed a pattern of nigrostriatal dysfunction typical of idiopathic Parkinson's disease. 18F-dopa-PET scans in unaffected family members prior to identifying the disease locus did not detect subclinical nigrostriatal dysfunction. Olfaction was assessed in affected subjects and Lewy bodies were identified in the olfactory bulb as well as cortex and brainstem of one deceased patient. In order to assess the role of mutations in this gene in other familial cases we undertook a mutation screen of all 51 exons of LRRK2 in 117 other smaller British kindreds with familial Parkinson's disease. The commonest mutation was G2019S and we also identified two novel mutations, R1941H and T2356I, in the coding sequence. These data suggest that parkinsonism caused by mutations in LRRK2 is likely to represent the commonest locus for autosomal dominant Parkinson's disease with a phenotype, pathology and in vivo imaging similar to idiopathic, late-onset Parkinson's disease.
 ...
PMID:Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data. 1631 Dec 69

We report on seven children (five males, two females) who presented with marked, often asymmetrical, toe-walking from onset of independent walking, associated with abnormal foot postures and increased tone at the ankles with characteristics of dystonia. Most of the children had presented with unusual pre-walking locomotion and a mild delay in independent walking. They did not fit into the usual categories of 'habitual' toe-walking or congenital short tendo calcaneus but nor did they have the clinical signs of spastic diplegia or of a peripheral neuromuscular disease. Normalization occurred progressively in the second to fourth years of life. The children were re-examined several years later (1 to 11y) and were normal. We believe that their persistent toe-walking corresponded to a variant of 'transient focal dystonia of infancy'. Knowledge of its existence may justify a period of observation without special investigations, surgery, or casting.
 ...
PMID:Transient dystonic toe-walking: differentiation from cerebral palsy and a rare explanation for some unexplained cases of idiopathic toe-walking. 1720 82

A 60-year-old man presented with slowly progressive left hemi-Parkinsonism, left hand apraxia, myoclonus, dystonia, visuospatial disturbances, and alien limb phenomenon, resembling corticobasal syndrome. Eight years later, neuropathology revealed features of Alzheimer's disease, with asymmetrical (right more than left) cortical tau burden with image analysis. The videotaped clinical features, neuropsychological aspects, and neuropathological correlates are presented and discussed.
 ...
PMID:Alzheimer's disease presenting as corticobasal syndrome. 1809 77

Corticobasal degeneration (CBD) is a rare neurodegenerative disorder characterized by distinctive clinical manifestations including asymmetric akinetic-rigid syndrome and higher cortical dysfunctions. We characterized the clinical, electrophysiological and imaging presentations in four patients with CBD. All patients exhibited unilateral hand dystonia, rigidity and apraxia, but showed no significant response to levodopa therapy. Surface electromyography demonstrated short duration and stimulus-sensitive myoclonus in three of the four patients. On the other hand, there was no "giant" SEPs (somatosensory evoked potentials), and the backaveraged electroencephalography did not show any jerk-locked cortical potentials. Brain magnetic resonance imaging showed asymmetrical cortical atrophy. [99mTc]HMPAO single-photon emission computed tomography (SPECT) revealed decreased regional cerebral blood flow in the frontoparietal areas and thalamus opposite to the more severely affected limb. [99mTc]TRODAT-1 SPECT showed decreased uptake in the striatum of the affected hemisphere. These data supported that there are abnormal cortical excitability and asymmetric pathological change of the affected hemisphere in the patients with CBD.
 ...
PMID:Clinical, imaging and electrophysiological studies of corticobasal degeneration. 1748 28

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

Myoclonic jerks and myoclonic status (MS) are sometimes difficult to distinguish clinically from movement disorders such as hand stereotypies, tremor, and dystonia in Rett syndrome. We describe a rare and complete video-polygraphic study of a girl with Rett syndrome (MECP2 mutation) and MS misdiagnosed as movement disorders and disclosed after video-polygraphic recordings. Corresponding to closely recurring activity of diffuse spike and polyspikes-wave-type paroxysms, rhythmic and, especially, arrhythmic myoclonias, usually asymmetrical and asynchronous, involving mainly right muscle deltoid and rarely followed by an inhibitory phenomenon, appeared. The MS improved and, most importantly, disappeared after the use of levetiracetam, with an evident antimyoclonic efficacy and a marked improvement of daily life for the patient and her caregivers. The difficulty in differentiating some typical nonepileptic behavioral features and movement disorders of patients with Rett syndrome from seizures was overcome using prolonged video-polygraphic recordings in our case.
 ...
PMID:Myoclonic status misdiagnosed as movement disorders in Rett syndrome: a video-polygraphic study. 1960 60

Patients with focal dystonia exhibit proprioception abnormalities that can lead to kinematic deficits. Proprioceptive abnormalities are present in both symptomatic and asymptomatic body parts of dystonic patients. To ascertain whether in patients with idiopathic cervical dystonia (CD) movements performed with nondystonic segments display kinematic abnormalities, we studied trajectory formation of out and back arm reaching movements in 10 patients with CD (before and 3 weeks after treatment with Botulinum toxin) and in 10 age-matched controls. Before treatment, patients with CD showed significant trajectory abnormalities when compared with normal controls. Patients' trajectories were more curved with asymmetrical temporal velocity profiles as well as increased hand path areas, and had longer reversal lags between the out and back segments. Treatment with botulinum toxin improved all the kinematic parameters. These results suggest that in patients with CD, movements performed with nondystonic segments are abnormal. The kinematic abnormalities are likely to derive from long-standing defective integration of the proprioceptive input, which, in turn, causes general changes in the internal models of limb dynamics. It is plausible that treatment with botulinum toxin partially restores proprioceptive processing and thus, such internal models.
 ...
PMID:Cervical dystonia affects aimed movements of nondystonic segments. 1960 7

Corticobasal degeneration (CBD) is an uncommon, sporadic, neurodegenerative disorder of mid- to late-adult life. We describe a further example of the pathologic heterogeneity of this condition. A 71-year-old woman initially presented dysarthria, clumsiness, progressive asymmetric bradykinesia, and rigidity in left arm. Rigidity gradually involved ipsilateral leg; postural instability with falls, blepharospasm, and dysphagia subsequently developed. She has been previously diagnosed as unresponsive Parkinson's Disease. At our clinical examination, she presented left upper-arm-fixed-dystonia, spasticity in left lower limb and pyramidal signs (Babinski and Hoffmann). Brain MRI showed asymmetric cortical atrophy in the right frontotemporal cortex. Neuropsychological examination showed an impairment in visuospatial functioning, frontal-executive dysfunction, and hemineglect. This case demonstrates that association of asymmetrical focal cortical and subcortical features remains the clinical hallmark of this condition. There are no absolute markers for the clinical diagnosis that is complicated by the variability of presentation involving also cognitive symptoms that are reviewed in the paper. Despite the difficulty of diagnosing CBD, somatosensory evoked potentials, motor evoked potentials, long latency reflexes, and correlations between results on electroencephalography (EEG) and electromyography (EMG) provide further support for a CBD diagnosis. These techniques are also used to identify neurophysiological correlates of the neurological signs of the disease.
 ...
PMID:An unusual cause of dementia: essential diagnostic elements of corticobasal degeneration-a case report and review of the literature. 2178

Corticobasal syndrome (CBS) is characterised by asymmetrical parkinsonism and cognitive impairment. The underlying pathology varies between corticobasal degeneration, progressive supranuclear palsy, Alzheimer's disease, Creutzfeldt-Jakob disease and frontotemporal lobar degeneration sometimes in association with GRN mutations. A 61-year-old male underwent neurological examination, neuropsychological assessment, MRI, and HMPAO-SPECT at our medical centre. After his death at the age of 63, brain autopsy, genetic screening and mRNA expression analysis were performed. The patient presented with slow progressive walking disabilities, non-fluent language problems, behavioural changes and forgetfulness. His family history was negative. He had primitive reflexes, rigidity of his arms and postural instability. Later in the disease course he developed dystonia of his left leg, pathological crying, mutism and dysphagia. Neuropsychological assessment revealed prominent ideomotor and ideational apraxia, executive dysfunction, non-fluent aphasia and memory deficits. Neuroimaging showed symmetrical predominant frontoparietal atrophy and hypoperfusion. Frontotemporal lobar degeneration (FTLD)-TDP type 3 pathology was found at autopsy. GRN sequencing revealed a novel frameshift mutation c.314dup, p.Cys105fs and GRN mRNA levels showed a 50% decrease. We found a novel GRN mutation in a patient with an atypical (CBS) presentation with symmetric neuroimaging findings. GRN mutations are an important cause of CBS associated with FTLD-TDP type 3 pathology, sometimes in sporadic cases. Screening for GRN mutations should also be considered in CBS patients without a positive family history.
 ...
PMID:Symmetrical corticobasal syndrome caused by a novel C.314dup progranulin mutation. 2186 16


<< Previous 1 2 3 Next >>