Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirteen patients suffering from motor neuron disease with dementia were studied to analyze the clinicopathological spectrum. The diagnosis of the disease was made on the basis of a clinical history of progressive dementia and motor neuron involvement. The mean age at onset of 11 sporadic cases was 54.9 years (range, 43 to 69 years), with a mean duration of disease of 25 months (range, 11 to 47 months). The initial symptoms were dementia in 7 cases, motor neuron involvement in 2 cases, and both dementia and motor neuron involvement in 2 cases. The clinical picture of motor neuron disturbance in sporadic cases represented bulbar-type of amyotrophic lateral sclerosis (ALS). Bulbar palsy was the initial symptom in 7 sporadic cases and all 11 patients developed bulbar palsy with advancing course of illness. Muscular wasting and fasciculation were more predominant in the upper limbs, shoulder girdle and anterior chest. Fasciculation was more extensively and frequently observed in those portions than that of classical ALS. In contrast, muscle strength in the lower limbs was well preserved so that all patients could walk even when respiratory failure developed. Hyperreflexia including jaw jerk was found in all cases and positive Babinski sign in 7 cases. Parkinsonism appeared in the initial stage in one sporadic case and in two familial cases. The type of dementia with uninhibited behavior and personality change closely mimicked that of Pick's disease. The degree of dementia was mild or moderate in 8 cases and severe in 3 cases. Language disorder was characterized by progressive reduction of speech output, leading finally to mutism in 5 cases. Perseveration was observed in 10 cases. Visuospatial disorder was absent even in the advanced stage. Mild memory disturbance was noted in the early stage in 10 cases. Pathological examination was performed in 7 cases including one familial case, revealing frontal atrophy in 3 cases, frontotemporal atrophy in 2 cases and temporal atrophy in 2 cases. On microscopic examination there were mild neuronal loss, gliosis, mild spongy state of the cortical superficial layers and fibrous gliosis in the frontotemporal white matter. The scattered senile plaques in one case did not justify a diagnosis of Alzheimer's type dementia. Neither circumscribed atrophy nor Pick body was found in any case. The nucleus basalis of Meynert showed no neuronal loss. The substantia nigra showed a mild to severe loss of nerve cells without Lewy bodies in all cases.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[A clinicopathological study on 13 cases of motor neuron disease with dementia]. 130 19

The association of Pick's Disease (PD) and Amyotrophic Lateral Sclerosis (ALS) as a familial syndrome is reported for the first time. Four members in two generations of the investigated family suffered from this syndrome, allowing the hypothesis of a dominant mode of inheritance. PD is primary, with onset at 58 to 67 years: loss of interests, depression, aggressivity, perseveration , stereotypies, reduction of speech until total mutism; a few months later appear ALS signs: fasciculations and/or pyramidal symptoms. The total evolution is 3 to 5 years. The brain showed a fronto-temporal atrophy spreading to the precentral gyrus with cortical and white matter gliosis, neuronal loss, atrophic neurons and some ballooned cells, but without senile plaques (SP), neurofibrillary tangles (NFT) or cortical spongiosis; the spinal cord and the medulla oblongata showed typical ALS lesions; mild lesions in the basal nuclei, particularly in the substantia nigra and the pallidum. The differential diagnosis is discussed with: Alzheimer's Disease + ALS (SP + NFT); the Guam syndrome (NFT); Creutzfeldt-Jakob's Disease (cortical microspongiosis); ALS + dementia (primary ALS); Mitsuyama's syndrome (primary dementia and secondary ALS, but with cortical spongiosis and without familial incidence).
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PMID:[A familial syndrome: a combination of Pick's disease and amyotrophic lateral sclerosis]. 332 1

Patients with amyotrophic lateral sclerosis were treated with high-dose intravenous infusion of human leukocyte interferon for six days. Neuropsychological examinations were carried out before, during and after the treatment. Marked reversible dysfunction was detected in immediate memory functions, coordination of hand movements, and drawing. Motor perseveration, micrographia, and slowing of behaviour were also observed. Changes appeared four to 12 days after start of treatment, with the peak on days six to eight. Recovery was almost complete by day 15. Intellectual ability, as measured by three WAIS subtests, praxis of hand movements, visuognostic functions, speech, reading, writing, and calculation remained essentially unaffected. The profile of the neuropsychological deficits observed, the absence of defects typical of focal posterior cortical lesions, the simultaneously slowed electroencephalographic activity with frontal accentuation, and the increased central conduction times of brain stem auditory evoked potentials suggest frontobasal involvement.
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PMID:Memory and psychomotor impairment following high-dose interferon treatment in amyotrophic lateral sclerosis. 408 13

The topographic distribution of degenerative changes in large brain sections from five sporadic amyotrophic lateral sclerosis (ALS) patients with dementia and three without dementia was examined. The dementia characteristics were impaired shifting from one line of thinking to another, perseveration, and emotional disinhibition as well as impairment of cognition, and judgment. Neuropathological examinations showed definite ALS changes in all the patients studied. In addition, the five patients with dementia showed neuronal loss, gliosis, and sponginess of the superficial layers throughout the cerebral cortices, predominantly in the dorsomedial cortex of the temporal tip and the parahippocampal, ambiens, anterior cingulate, rectal, orbital, and insular gyri as well as neuronal loss in the basolateral nucleus of the amygdala, nucleus accumbens, and subiculum of the hippocampus. Ubiquitin-immunoreactive inclusions were present in some neurons in the granular cell layers of the hippocampus. Fibrous gliosis was extensive in the subcortical and deep white matter of the frontotemporal lobes. The affected regions take in the limbic system and its associated areas which are the sources of the psychological problems, including emotional disturbance, experienced by these ALS patients. The psychological problems of ALS need to be investigated in relation to the involvement of the limbic system.
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PMID:Participation of the limbic system and its associated areas in the dementia of amyotrophic lateral sclerosis. 783 49

Amyotrophic lateral sclerosis (ALS) with dementia is characterized by rapidly progressive dementia and motor neuron involvement. The age at onset in 12 sporadic cases ranged from 43 years to 78 years. The initial symptoms are dementia, such as uninhibited behavior and personality change in most patients. Both dementia and motor neuron involvement appear within 1 or 2 years of the onset. The clinical picture of motor neuron disturbance was bulbar-type ALS. In ALS-dementia, lower motor neuron sign is predominant than upper motor neuron sign. The pattern of dementia indicated impaired frontal lobe function, confirmed by frontal sign such as perseveration, forced grasping and utilization behavior. These neurological signs are significant in association with the frontal lesion on CT, MRI and single photon emission computed tomography. The pathological findings show frontotemporal atrophy, mild non-specific neuronal loss of cortical superficial layer, fibrous gliosis of subcortical white matter, degeneration of substantia nigra and motor neuron involvement. The clinicopathological findings resembled those of dementia of frontal type and are distinct from those of Alzheimer's disease. We thus consider that the combination of motor neuron disease and dementia is a new clinicopathological entity, quite distinct from ALS or other dementias, as Yuasa and Mitsuyama proposed earlier.
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PMID:[Reappraisal of amyotrophic lateral sclerosis with dementia]. 875 63

Frontotemporal dementia (FTD)-a common clinical manifestation of frontotemporal lobar degeneration (FTLD)--is characterized by alterations in personality and social conduct. Its symptoms include inertia, loss of volition, social disinhibition, and distractibility, with relative preservation of memory and visuospatial function. We present the typical case of patient with typical clinical symptoms including "going my way" behavior, inactivity, lack of awareness of illness, stereotypic behavior, perseveration, and environmental dependency syndrome. These clinical symptoms can be interpreted on the basis of extent of damage to the frontal lobes and the interaction between the frontal lobes and other neural systems such as the posterior association cortices, basal ganglia or limbic systems. We also address several complex clinical issues, including the relationship between clinical manifestations and pathological findings, underestimation of FTD in patients with amyotrophic lateral sclerosis (ALS) and/or motor neuron disease (MND), and impairment in a single cognitive domain such as isolated agraphia in ALS/MND and FTD. To address these problems, it is essential to observe the clinical symptoms in patients with FTD and ALS/MND in detail and to compare clinical characteristics with pathological findings. It is also critical to develop clinical tests that minimize the impact of speech and motor dysfunction on performance, particularly on the basis of a longitudinal analysis.
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PMID:[Symptoms of frontotemporal dementia]. 1993 79

The ability to reject an automatic tendency, i.e. inhibition, has been linked to the prefrontal cortex, but its neural underpinnings are still controversial. Neurodegenerative diseases represent an interesting model to explore this issue, given its frequent impairment in these disorders. We investigated the inhibitory impairment and its neural basis using four different tests, which evaluate the presence of inhibitory dysfunction (Stroop test, Hayling test, and two graphical perseveration tests), and assessed their correlation with brain metabolism using 18F-fluorodeoxyglucose positron emission tomography in a group of 76 participants with behavioral variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and healthy controls (HC). Inhibition impairment was more frequent in bvFTD and AD, than ALS and HC. AD and bvFTD only differed in the strategy used in Hayling test, and the frequency of impairment in graphical perseveration tests. Correlation between inhibition tests was moderate. The Stroop test correlated with several regions of the frontal and parietal lobes, mainly on the left side. Hayling test correlated with almost all regions of the frontal lobe and, especially, with the orbitofrontal cortex. Some differences in the impaired regions in each disease were found. Inhibition ability was mainly impaired in bvFTD and AD, and it correlated with the bilateral frontal lobe metabolism. There were certain particularities according to the specific task and patients evaluated. These dissimilarities may support the concept of inhibition as a multidimensional construct, with the involvement of common and divergent neural mechanisms.
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PMID:Inhibition impairment in frontotemporal dementia, amyotrophic lateral sclerosis, and Alzheimer's disease: clinical assessment and metabolic correlates. 2974 71

Perseveration and apathy are two of the most common behavioural and psychological symptoms of dementia (BPSDs) in amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD). Availability of a validated and behaviourally characterised animal model is crucial for translational research into BPSD in the FTD context. We behaviourally evaluated the male TDP-43Q331K mouse, an ALS-FTD model with a human-equivalent mutation (TDP-43Q331K) knocked into the endogenous Tardbp gene. We utilised a panel of behavioural tasks delivered using the rodent touchscreen apparatus, including progressive ratio (PR), extinction and visual discrimination/reversal learning (VDR) assays to examine motivation, response inhibition and cognitive flexibility, respectively. Relative to WT littermates, TDP-43Q331K mice exhibited increased responding under a PR schedule. While elevated PR responding is typically an indication of increased motivation for reward, a trial-by-trial response rate analysis revealed that TDP-43Q331K mice exhibited decreased maximal response rate and slower response decay rate, suggestive of reduced motivation and a perseverative behavioural phenotype, respectively. In the extinction assay, TDP-43Q331K mice displayed increased omissions during the early phase of each session, consistent with a deficit in activational motivation. Finally, the VDR task revealed cognitive inflexibility, manifesting as stimulus-bound perseveration. Together, our data indicate that male TDP-43Q331K mice exhibit a perseverative phenotype with some evidence of apathy-like behaviour, similar to BPSDs observed in human ALS-FTD patients. The TDP-43Q331K knock-in mouse therefore has features that recommend it as a useful platform to facilitate translational research into behavioural symptoms in the context of ALS-FTD.
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PMID:Coexistence of perseveration and apathy in the TDP-43Q331K knock-in mouse model of ALS-FTD. 3314 10