Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Classical striatal symptoms were interpreted through identification of the underlying projection system, by physiological analysis of neuronal activity of each subnucleus in the base of the thalamus during stereotactic procedures for various involuntary movements. Rigidity, levodopa-induced dyskinesia, idiopathic dyskinesia, symptomatic athetoid movement and symptomatic choreic movement, as well as that in Huntington's disease, belong to the category of striatal symptoms. These symptoms may be alleviated by surgery on the pallido-Vo-complex projection, which is the main output affected by disorders due to striatal dysfunction.
 ...
PMID:Striatal symptoms. 265 43

Dopamine, noradrenaline, glutamic acid decarboxylase and choline acetyltransferase were measured in various regions of brain obtained at autopsy from a large series of cases of Huntington's chorea, dying with advanced forms of the disease. Neurochemical values in the choreic cases were compared with those from control and schizophrenic cases. In brain tissue from choreic patients, highly significant increases in dopamine concentrations were found in the corpus striatum, nucleus accumbens and pars compacta of the substantia nigra. This is consistent with the hypothesis that the nigrostriatal dopamine system is spared and may exert a relatively unopposed action on striatal function. Noradrenaline concentrations were raised in the caudate nucleus, lateral pallidum and pars reticulata of the substantia nigra, indicating preservation of central noradrenergic pathways. Glutamic acid decarboxylase activity was reduced in all brain regions examined but, taking ante-mortem factors into account, the depletion was confined to the striatum and lateral pallidum. This is consistent with the view that striatal GABA-containing interneurons degenerate. Significant losses of choline acetyltransferase activity were observed in the striatum, nucleus accumbens, septal nuclei and hippocampus. The development of muscle rigidity in choreic patients did not significantly affect the neurochemical values. The neurochemical alterations in Huntington's chorea could not be attributed to differences in ante-mortem or post-mortem factors between the choreic group and the control and schizophrenic groups.
 ...
PMID:Neurochemical alterations in Huntington's chorea: a study of post-mortem brain tissue. 610 90

An autopsy case with clinically and molecular genetically diagnosed Huntington's disease (HD) accompanied with minimal non-specific neuropathological features was reported. When the patient was 45 years old, he had faulty memory, mood swing, personality change and agitation. Neurological and psychiatric examinations revealed choreoathetoid movements in limbs and trunk, generalized hyperreflexia and mental deterioration. However, cerebellar ataxia and muscle rigidity were not disclosed. Neuroimaging study did not show a definite atrophy of heads of caudate nuclei. Neuroacanthocytosis and Wilson's disease were ruled out by the peripheral blood examination and serum Cu and ceruloplasmin examination. At the age of 55 he died of pneumonia. Post-mortem examination revealed minimal non-specific neuropathological features for HD (Vonsattel's grade 0), that is, no visible fibrillary gliosis in the striatum, and few neuronal loss and only proliferation of astrocytes (astrocytosis) in the striatum. Molecular-genetic study the patient's brain tissues and his youngest son's blood was performed. These studies revealed 40 CAG repeats in the patient, 56 CAG repeats in his youngest son. These results suggest they may be HD. Vonsattel et al. [ 1998] insist that grade 0 comprises 1% of all HD brains, and grade 1 comprises 4% of all HD brains. But we could not find any reports in which the clinical and neuropathological features were described in detail on the cases with clinically and molecular genetically diagnosed HD without specific pathological findings. Therefore, we present in detail the clinical and neuropathological features of such case.
 ...
PMID:An autopsy case with clinically and molecular genetically diagnosed Huntington's disease with only minimal non-specific neuropathological findings. 1074 90

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by high instability and extension of CAG sequences within the coding region of IT15 gene. It affects both sexes and age at onset of the disease may be different but usually occurs in midlife. The term Juvenile Huntington's disease is generally applied to 10% of the cases with onset before 20. We present clinical features and results of DNA analysis in 16 patients from 14 families aged 9 to 36. The age of onset was between 5 to 20 years; duration of the disease was from 2 to 16 years. In 10 cases the mutated gene was transmitted by the affected father; only in two cases by the mother. In all cases anticipation manifested by earlier onset of the disease in subsequent generations and expansion of CAG repeats was documented. The number of CAG repeats was between 50 and 92 (mean 67.3). Progressive mental deterioration, declining school performance, hyperactivity and emotional disturbances were the first symptoms of juvenile HD. Neuropsychological assessment showed mean IQ in Wechsler test 59.6 and Mini-Mental State Examination scores 22.8. Rigidity and bradykinesia were predominant features in the cases with juvenile onset, the remaining ones developed choreatic movements. Three persons had epileptic seizures; two (both females) revealed behaviour and psychiatric disturbances. Amplitudes of somatosensory evoked potentials, visual evoked potentials and brainstem auditory evoked potentials were markedly reduced. MRI of the brain showed atrophy of heads of the caudate nuclei, putamen and globus pallidus.
 ...
PMID:[Clinical and genetic study of juvenile form of Huntington's disease]. 1204 2

When Huntington's disease (HD) patients are tested on cognitive tasks that involve both striatal and hippocampal memory systems, a decline in their striatal function is compensated for by an increase in hippocampal activity that allows these patients to achieve an optimal performance [Voermans, N. C., Petersson, K. M., Daudley, L., Weber, B., van Spaendonck, K. P., Kremer, H. P. H., et al. (2004). Interaction between the human hippocampus and the caudate nucleus during route recognition. Neuron, 43, 427-435]. Our recent study suggests that there is also an imbalance between hippocampal and striatal memory systems in R6/2 mice, a widely used animal model of HD [Ciamei, A., & Morton, A. J. (2008). Rigidity in social and emotional memory in the R6/2 mouse model of Huntington's disease. Neurobiology of Learning and Memory, 89, 533-544]. However, interactions between multiple memory systems have never been studied directly in HD mice. Here, we used a water maze task to examine striatal and hippocampal systems directly. R6/2 mice were trained to swim from a fixed starting point to a cued platform. During the probe test, the apparatus was rotated by 180 degrees, and mice had to choose between a hidden platform located where the cued platform had been during training (place learning), and a cued platform that was now located in the opposite quadrant (cue learning). Probe trial results showed that in 8 week old R6/2 mice the escape response was driven mainly by a cue-based strategy (striatal), whereas by 12 weeks of age, a higher proportion of mice adopted a place-based strategy (hippocampal) to escape from the maze. We conclude that following striatal decline in R6/2 mice between 8 and 12 weeks of age, hippocampal functions emerge to drive the escape response of R6/2 mice.
 ...
PMID:Progressive imbalance in the interaction between spatial and procedural memory systems in the R6/2 mouse model of Huntington's disease. 1952 96

Dementia is a subject of interest for both neurologists and psychiatrists. The most common causes of dementia are neurodegenerative diseases of the CNS. Alzheimer's disease is the most frequent of them, much less common are Lewy's body disease, Pick's disease, Parkinson's disease or Huntington's disease. Huntington's disease is an autosomally dominant terminal illness, that occurs in approximately 5 - 7 persons in 100 000. In 90% of the cases it begins after the age of 35, the remaining 10% is the juvenile and early form, which varies from that seen in adults. Rigidity, oral motor dysfunction, gait disorder and rapid cognitive decline are the main characteristics of the juvenile and early form. Chorea is rare or absent. The case of a young woman who developed dementia with motor and speech abnormalities is presented in this paper. Due to the great non-specifity of the symptoms she was being diagnosed for about 2 years (hospitalized 3 times in the neurology wards and 4 times in the psychiatry wards). Lack of family history disorders, no specific abnormalities in neurological examination, abundance of traumatic experiences accounted for the preliminary diagnosis of a dissociative disorder (pseudodementia). Many symptoms, such as depression, obsessive-compulsive disorder, personality and behavioural disturbances were observed in the course of the disease. Finally, after 6 years from the appearance of the first symptoms, based on the third MR of CNS, the diagnosis of the early HD was established. The genetic test confirmed it.
 ...
PMID:[Early Huntington disease as a cause of dementia in a 34 year old woman]. 1989 66

The striatum serves as the main input to the basal ganglia, and is key for the regulation of motor behaviors, compulsion, addiction, and various cognitive and emotional states. Its deterioration is associated with degenerative disorders such as Huntington's disease. Despite its apparent anatomical uniformity, it consists of intermingled cell populations, which have precluded straightforward anatomical sub-classifications adhering to functional dissections. Approximately 95% of the striatal neurons are inhibitory projection neurons termed medium spiny neurons (MSNs). They are commonly classified according to their expression of either dopamine receptor D1 or D2, which also determines their axonal projection patterns constituting the direct and indirect pathway in the basal ganglia. Immunohistochemical patterns have further indicated compartmentalization of the striatum to the striosomes and the surrounding matrix, which integrate MSNs of both the D1 and D2 type. Here, we present a transgenic mouse line, Gpr101-Cre, with Cre recombinase activity localized to matrix D1 and D2 MSNs. Using two Gpr101-Cre founder lines with different degrees of expression in the striatum, we conditionally deleted the vesicular inhibitory amino acid transporter (VIAAT), responsible for storage of GABA and glycine in synaptic vesicles. Partial ablation of VIAAT (in ~36% of MSNs) resulted in elevated locomotor activity compared to control mice, when provoked with the monoamine reuptake inhibitor cocaine. Near complete targeting of matrix MSNs led to profoundly changed motor behaviors, which increased in severity as the mice aged. Moreover, these mice had exaggerated muscle rigidity, retarded growth, increased rate of spontaneous deaths, and defective memory. Therefore, our data provide a link between dysfunctional GABA signaling of matrix MSNs to specific behavioral alterations, which are similar to the symptoms of Huntington's disease.
...
PMID:Conditional targeting of medium spiny neurons in the striatal matrix. 2587 May 47

Juvenile Huntington's disease (JHD) is a neurodegenerative disease with onset prior to the age of 21. While it accounts for a relatively small proportion of Huntington's disease (HD) diagnoses, its impact is significant on the quality of life for those affected. Clinicians may be unaware that HD can present in childhood and adolescence, delaying diagnosis. HD develops due to an expanded CAG repeat in the huntington gene. Rigidity, dystonia, and seizures are more common in JHD. Cognitive changes such as executive function impairments and decline in school performance are common. The burden of psychiatric symptoms is considerable and includes depression, anxiety, impulsivity, and aggression. While novel approaches to treatment interventions are investigated, current care is limited to targeting symptoms rather than disease modification. Prompt diagnosis and symptomatic treatment can maximize quality of life for these patients.
 ...
PMID:Juvenile Huntington's Disease: Diagnostic and Treatment Considerations for the Psychiatrist. 2816 95