Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of cognitive impairment in corticobasal degeneration (CBD) is now widely recognised. Our review of the literature reveals that, although the pattern and severity of neuropsychological impairments can be highly variable across patients, several general trends can be identified. The most characteristic impairments are limb apraxia (usually ideomotor), constructional and visuospatial difficulties, acalculia, frontal dysfunction, and nonfluent aphasia. The limb apraxia is associated with deficits in drawing, copying, and handwriting, but there is emerging evidence that the problems with handwriting are not due exclusively to the apraxia. The findings with respect to episodic memory are more variable, but when there is impairment in this area, it tends to be milder than that seen in Alzheimer's disease. Semantic memory functioning appears relatively preserved but has been poorly studied. Problems with speech are common, and may be due to dysarthria or buccofacial apraxia. Aphasia, although initially considered rare, is in fact a common accompaniment of CBD, may be the presenting feature, and is typically nonfluent in type. More systematic investigation of the clinical and neuropathological overlap between progressive nonfluent aphasia (generally considered to be a form of frontotemporal dementia) and CBD is needed.
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PMID:Corticobasal degeneration as a cognitive disorder. 1463 61

A four-generation pedigree exhibiting early-onset autosomal dominant Alzheimer disease (AD) with spastic paraplegia, dystonia, and dysarthria due to a novel 6-nucleotide insertional mutation in exon 3 of the presenilin 1 gene (PS1) is described. Serial examinations, PET scans, and autopsy revealed that the mutation in this highly conserved portion of PS1 causes an aggressive dementia that maintains the usual regional hierarchy of disease pathology while extending abnormalities into more widespread brain areas than typically seen in AD.
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PMID:Novel insertional presenilin 1 mutation causing Alzheimer disease with spastic paraparesis. 1515 97

Like Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which a very defined population of neurons selectively degenerates. Muscular atrophy and central paresis develop in ALS patients relatively quickly--usually within months to a few years. Bulbar symptoms such as swallowing disorders and dysarthria are frequently observed in the beginning. The disease progresses steadily and without remission. The average length of survival after diagnosis is two to three years. The diagnosis is made on the basis of a characteristic group of symptoms and confirmed or substantiated through additional clinical neurological tests. Currently, the cause of the disease cannot be treated. Treatment concentrates primarily on symptomatic measures and providing supportive devices.
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PMID:[Diagnosis and treatment of amyotrophic lateral sclerosis]. 1772 75

Progressive nonfluent aphasia (PNFA) is a clinical syndrome characterized by motor speech impairment and agrammatism, with relative sparing of single word comprehension and semantic memory. PNFA has been associated with the characteristic pattern of left anterior insular and posterior frontal atrophy, including the motor and premotor regions and Broca's area. Postmortem histopathologic evidence has shown that PNFA is usually associated with tau pathology, although focal Alzheimer disease pathology and tau-negative, ubiquitin-TDP-43 inclusions also have been reported in association with this clinical syndrome. We performed a detailed analysis of motor speech errors in 18 patients with PNFA and investigated their neural correlates using voxel-based morphometry on magnetic resonance imaging scans. Seven patients demonstrated only apraxia of speech (AOS) errors, whereas 11 showed AOS along with dysarthria. Slow rate of speech, effortful articulation with groping, and consonant distortions were the most common AOS errors. Hypernasality was the most represented dysarthric feature and dysarthria was most often classified as spastic, hypokinetic, or mixed spastic-hypokinetic. Neuroimaging results demonstrated that patients with AOS-only and AOS plus dysarthria showed atrophy in the left posterior frontal, anterior insular, and basal ganglia regions when compared with controls. Patients with AOS plus dysarthria showed greater damage than patients with AOS-only in the left face portion of primary motor cortex and left caudate. PNFA is a distinct frontotemporal lobar degeneration clinical syndrome associated with characteristic clinical, neuroimaging, and pathologic features. The clinical features are driven by the severity of left frontal and caudate damage.
Alzheimer Dis Assoc Disord
PMID:Progressive nonfluent aphasia and its characteristic motor speech deficits. 1809 Apr 19

Progranulin gene (PGRN) mutations cause frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Patients usually present with a frontotemporal dementia syndrome and have prominent atrophy and neuronal loss in frontal and temporal cortices and the striatum, with neuronal intranuclear and cytoplasmic inclusions. Clinical, neuropathological, and genetic studies are reported on an individual with PGRN mutation and her family members. We describe a patient with a PGRN c.26C>A mutation who presented with progressive stuttering dysarthria, oculomotor abnormalities, choreic buccolingual movements, and mild parkinsonism. Two other family members were affected, one with a behavioral variant frontotemporal dementia syndrome, the other with a diagnosis of probable Alzheimer's disease. At autopsy there was no neuronal loss in the cortex or medial temporal lobe structures, but there was striatal gliosis. Immunohistochemistry for ubiquitin and TDP-43 revealed neuronal cytoplasmic and intranuclear inclusions as well as neurites. This study further expands the clinical and pathological spectrum of PGRN mutations, and suggests the diagnosis could be missed in some individuals with atypical presentations.
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PMID:Progranulin gene mutation with an unusual clinical and neuropathologic presentation. 1844 19

An increasing number of inherited neurodegenerative diseases are known to be caused by the expansion of unstable trinucleotide repeat tracts. Spinocerebellar ataxia type 8 (SCA8) has been identified as being partly caused by a CTG expansion in an untranslated, endogenous antisense RNA that overlaps the Kelch-like 1 (KLHL1) gene. Clinically, SCA8 patients show similar features to those with the other SCAs, including limb and truncal ataxia, ataxic dysarthria and horizontal nystagmus, all of which are signs of dysfunction of the cerebellar system. However, allele sizes within the SCA8 proposed pathogenic range have been reported in patients with ataxia of unknown etiology, in individuals from pedigrees with other SCA or Friedreich's ataxia, and in patients with Alzheimer's disease, schizophrenia or parkinsonism. These observations suggest that mutation of the SCA8 locus might affect neurons other than the cerebellum. Antisense transcripts are known to regulate complementary sense transcripts and are involved in several biologic functions, such as development, adaptive response, and viral infection. In order to test whether SCA8 affects the KLHL1 expression by antisense RNA in brain cells, we examined the expression pattern of KLHL1 and SCA8 in human tissues and in mouse brain regions. SCA8 expression was colocalized with KLHL1 transcript in many brain regions whose functions are correlated to the clinical symptoms of SCA8 patients. These findings lead to the hypothesis of a possible relevance that SCA8 transcript downregulates KLHL1 expression through an antisense mechanism, which then leads to SCA8 neuropathogenesis.
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PMID:SCA8 mRNA expression suggests an antisense regulation of KLHL1 and correlates to SCA8 pathology. 1870 37

It has become increasingly apparent, especially with the advent of MRI brain scanning, that a large number of patients develop signal intensity changes in the subcortical white matter and periventricular region as they age. This appears to be accelerated by risk factors for small vessel cerebrovascular disease such as hypertension, smoking, diabetes mellitus and hyperlipidemia. The major question becomes when such changes become clinically significant. It is obvious that subcortical lacunar-type infarction can be identified by the clinical presentation. For example, typical examples of so-called "lacunar syndrome" include pure motor hemiparesis, pure sensory stroke, sensorimotor stroke, clumsy hand-dysarthria, and hemiataxia-hemiparesis. The issue becomes a measure of impact on functional ability. This is influenced by several factors. Baseline IQ and educational level, as well as expectations of age, certainly play a role. A person who develops cognitive impairment and long tract signs in their 50s or 60s is certainly going to be recognized as more impaired than an 80 year old individual who is retired and primarily is engaged in recreational activity. It would be expected that a person born with limited intellectual capacity and/or limited educational opportunity would be less likely to be identified as impaired than a person who has achieved substantial economic achievement through their innate talents. The concept of tissue loss or lesion load becomes important when determining how pronounced the ischemic cerebrovascular changes translate into functional impairment. Correlative pathology may include cortical atrophy and ventricular dilatation. Loss of either cortical or subcortical tissue function is expected to be related to functional compromise. In addition, there are potential features such as the coexistence of small vessel cerebrovascular disease and Alzheimer's disease. Small vessel cerebrovascular disease might also play a contributing factor in patients susceptible to Dementia with Lewy Bodies or patients susceptible to fronto-temporal dementia or any other dementing process. Thus, the concept of tissue loss or lesion burden of disease becomes increasingly important as we recognize the potential for multifactorial issues, including genetic factors, to contribute to the phenotypic expression. The relationships between cognitive impairment, dementia and subcortical vascular lesions are poorly understood. There have been several papers on the different aspects of cerebral insults and their impact on cognition, the various kinds of dementia and different methods of analyzing the impact of the various insults to the brain. This chapter is an attempt to review all pertinent information currently available on the poorly understood condition of "subcortical ischemic cerebrovascular dementia."
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PMID:Subcortical ischemic cerebrovascular dementia. 1950 11

We describe a case of late onset neurodegeneration with brain iron accumulation (NBIA) presenting as frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS). A male patient presented at age 66 with change of personality: disinhibition, emotional blunting, and socially inappropriate behavior, coupled with dysarthria, dystonia, and corticospinal tract involvement. Magnetic resonance imaging showed general cortical atrophy, iron deposits in the globus pallidus, and the "eye of the tiger" sign. Neuropsychologic performance was globally reduced, especially executive functions. Fluorodeoxyglucose positron emission tomography showed hypometabolism predominantly in frontal and temporal areas. Repeated neurophysiologic examinations showed signs of chronic denervation. The patient was diagnosed with NBIA but fulfilled consensus criteria for FTD and had a clinical picture of ALS, without neurophysiologic confirmation. Our finding introduces NBIA as a possible cause of FTD and as a differential diagnosis of the FTD-ALS complex.
Alzheimer Dis Assoc Disord
PMID:Frontotemporal dementia-amyotrophic lateral sclerosis complex is simulated by neurodegeneration with brain iron accumulation. 1956 52

Progressive nonfluent aphasia (PNFA) is one of the 3 clinical presentations of frontotemporal lobar degeneration (FTLD), the other 2 being frontotemporal dementia and semantic dementia (SD). PNFA and SD, both representing relentlessly progressive language impairment in the realm of FTLD, may share a large part with primary progressive aphasia (PPA). A salient distinction between PPA and PNFA or SD is that PPA includes another clinical type, namely, logopenic/phonemic aphasia (LPA), which is not represented in FTLD. This is primarily because LPA is usually caused by Alzheimer's disease (AD) and the brunt of the lesion is localized at the left temporo-parietal region of the brain. Further, PNFA/SD should be limited to the clinical consequencies of FTLD while PPA is more generous with regard to its causal pathology. By definition, PNFA is an expressive language impairment which is characterized by effortful speech, phonemic errors, grammatical impairment, and word-finding difficulties. Reading and writing may be comparatively impaired. Comprehension of single word meaning is normal, while comprehension of sentencies may sometimes be impaired. PNFA should be differentiated from SD, LPA, and pure progressive apraxia of speech (AOS or alternatively referred to as aphemia or anarthria). SD may be distinguished from PNFA by virtue of its fluency, characteristic loss of word meaning and absence of agrammatism. LPA is similar to PNFA, yet differs in that there is preservation of grammatical skills and speech motor function that is devoid of AOS and/or dysarthria. AOS is an impairment at the level of speech motor programming without language impairment. Thus, there may be a double dissociation between AOS and PNFA i. e., PNFA may or may not accompany AOS and vice versa. PNFA is associated with a localized lesion in the left frontotemporal area of the brain. Immunohistochemical investigations have revealed that ubiquitin/TAR DNA binding protein-43 (TDA-43) positive and tau negative pathology, mostly FTLD with ubiquitin-positive inclusions (FTLD-U) type 3, accounts for 90% of PNFA cases, while the remaining 10% may be caused by tauopathy. Therapeutic attempts for PNFA are currently unsuccessful.
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PMID:[Clinical types of FTLD: progressive nonfluent aphasia; comparative discussions on the associated clinical presentations]. 1993 81

The importance of designating criteria for diagnosing dementia lies in its implications for clinical treatment, research, caregiving, and decision-making. Dementia diagnosis in Huntington's disease (HD) is often based on criteria developed for Alzheimer's disease requiring memory loss. However, it is likely that other cognitive deficits contribute to functional impairment in HD before memory declines. The goal is to identify cognitive deficits that contribute to functional impairment to support dementia criteria that reflect HD neuropathology. Eighty-four HD mutation-positive subjects completed neuropsychological tests and the Unified Huntington's Disease Rating Scale Functional Independence Scale (FIS). Functional impairment was defined as 80 or below on the FIS. Speed of processing, initiation, and attention measures accounted for 70.0% of the variance in FIS ratings (linear regression) and correctly classified 91.7% of subjects as functionally impaired or intact (logistic regression). Measures of memory, motor impairment except dysarthria, neuroleptic use, and depressed mood did not improve prediction. A definition of HD dementia that includes cognitive impairment in at least two areas of cognition but does not require a memory deficit, in the context of impaired functional abilities and a deteriorating course, more accurately reflects HD neuropathology and could lead to improved research methods and patient care.
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PMID:Cognitive and functional decline in Huntington's disease: dementia criteria revisited. 2062 24


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