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)

We investigated the evolution of the neurological and neuropsychological characteristics in a right-handed woman who was 53-years-old at the onset and who showed personality changes and behavioral disorders accompanied by progressive dysarthria. She had hypernasality and a slow rate of speech with distorted consonants and vowels, which progressed as motor disturbances affecting her speech apparatus increased; finally, she became mute two years post onset. Her dysarthria due to bilateral voluntary facio-velo-linguo-pharyngeal paralysis accompanied with automatic-voluntary dissociation fit the description of anterior opercular syndrome. She showed personality changes and behavioral abnormalities from the initial stage of the disease, as is generally observed in frontotemporal degeneration (FTD), and her magnetic resonance image showed progressive atrophy in the frontotemporal lobes; thus, she was clinically diagnosed with FTLD. This patient's symptoms suggest that FTLD, including bilateral anterior operculum degeneration, causes progressive pseudobulbar paretic dysarthria accompanied by clinical symptoms of FTD, which raises the possibility of a new clinical subtype in the FTLD spectrum.
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PMID:A case of frontotemporal lobar degeneration with progressive dysarthria. 1687 20

We report a clinicopathological study of a patient suffering from frontotemporal dementia (FLD) with severe dysarthria and concomitant motor neuron disease (MND). The patient was a 52-year-old woman with almost simultaneous emergence of severe dysarthria and FTD. The severe dysarthria subsequently evolved into anterior opercular syndrome. Motor neuron signs then emerged, and the patient developed akinetic mutism approximately 2 years after the onset of the disease. The patient died of pneumonia after a 7-year clinical illness. Pathologically, severe and widespread degeneration in the frontal and temporal lobes, including the anterior opercular area, limbic system, basal ganglia, spinal cord and cerebellum, and frequent ubiquitin- and tau-negative basophilic inclusions were observed. The pyramidal tracts and anterior horns of the cervical cord also showed marked degeneration. Cases showing basophilic inclusions reported so far have been divided into two groups: early onset FTD and MND with basophilic inclusions. Our case presented clinicopathological features of both FTD and MND, which suggests that cases showing basophilic inclusions may constitute a clinicopathological entity of FTD/MND.
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PMID:An autopsy case of frontotemporal dementia with severe dysarthria and motor neuron disease showing numerous basophilic inclusions. 1708 Jul 24

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.
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PMID:Frontotemporal dementia-amyotrophic lateral sclerosis complex is simulated by neurodegeneration with brain iron accumulation. 1956 52

Basophilic Inclusion Body Disease (BIBD) is a tau-negative form of frontotemporal lobar degeneration (FTLD), characterized by neuronal cytoplasmic inclusions (NCI) that are visible on hematoxylin and eosin stain (HE), contain RNA, and are inconsistently ubiquitin-immunoreactive (ir). The normal nuclear expression of TDP-43 is not altered. Here we investigate whether the distribution of the structurally and functionally related protein fused in sarcoma (FUS) is altered in BIBD. Mutations in the FUS gene have recently been identified as a cause of familial amyotrophic lateral sclerosis (ALS). In addition to these familial ALS cases, FUS protein has recently been demonstrated in NCI in a subset of FTLD with ubiquitinated inclusions (atypical FTLD-U) and in neuronal intermediate filament inclusion disease (NIFID). We examined seven BIBD brains of patients with average age at onset 46 (range 29-57) and average duration of disease 8 years (range 5-12). Three cases presented with the behavioural variant of fronto-temporal dementia (FTD-bv) and one with FTD-bv combined with severe dysarthria. All four developed motor neuron disease/ALS syndrome (MND/ALS) several years later. In the other three cases, presentation was predominantly with motor symptoms, construed as MND/ALS in two, and progressive supranuclear palsy (PSP) in one. Severity of cortical degeneration varied, but all cases shared severe nigrostriatal atrophy and lower motor neuron pathology. In spared areas of cortex, FUS antibodies showed intense labelling of neuronal nuclei and weak positivity of cytoplasm, whereas, in affected areas, intense labelling of NCI was accompanied by reduction or disappearance of the normal IR pattern. The number of FUS-ir NCI was much greater than the number detected by HE or with ubiquitin or P62 immunohistochemistry. FUS-ir glial cytoplasmic inclusions (GCI) were abundant in the grey and white matter in all cases, whereas neuronal intranuclear inclusions were rare and only seen in 2/7 cases. Thus, BIBD shares with atypical FTLD-U and NIFID the presence of FUS-ir NCI and GCI, and together comprise a new biochemical category of neurodegenerative disease (FUS proteinopathies). The consistent involvement of motorneurons in BIBD indicates that the association of FTLD and MND/ALS can occur on a FUS or TDP-43 pathological substrate.
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PMID:FUS pathology in basophilic inclusion body disease. 1984 30

Two previously distinct leukodystrophies, pigmentary orthochromatic leukodystrophy and hereditary diffuse leukoencephalopathy with spheroids, have recently been interpreted as variants of the same disease, adult-onset leukoencephalopathy with spheroids and pigmented glia (ALSP). We report a sporadic case of a 56-year-old male with ALSP presenting as frontotemporal dementia behavioral variant (FTD-bv). He had a history of depression and developed socially inappropriate behaviors consistent with FTD-bv. His first neurological exam was normal, but he developed new symptoms in the next 1.5 years: executive functional difficulties, anosognosia, urinary incontinence, epilepsy, extrapyramidal syndrome, severe gait disturbance, dysarthria, dysphagia and mutism. He died of pneumonia 20 months after initial presentation. MRI revealed increased T2-FLAIR signal in periventricular white matter and corpus callosum atrophy. Histology showed extensive demyelination of the centrum semiovale, most severe in frontal and temporal lobes, sparing U-fibers. There was no cortical neuronal loss, but selective loss of thalamic neurons. Histopathological hallmarks were cortical neuronal ballooning, white matter orthochromasia, pigmented macrophages, oligodendroglial loss, and axonal spheroids, some myelinated and some vacuolated. Morphometric studies for myelin, spheroids, oligodendrocytes and astrocytes showed that: 1) spheroids were most abundant in areas of partial demyelination rather than areas of extensive demyelination, being absent in normal appearing areas, 2) oligodendrocyte loss only occurred in regions of extensive demyelination and not in partial demyelination, and 3) there was no statistically significant change in number of astrocytes. There were also many more spheroids than physiologically expected in the gracile and cuneate nuclei. These findings suggest that the formation of spheroids is an early-stage event in disease progression. *These authors contributed equally to this work.
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PMID:Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: report on a case with morphometric studies. 2358 69

A 76-year-old woman showed a dramatic lowering of her tone of voice in October 2014, followed by muscle weakness of the left arm. The previous attending physician noticed remarkable left dominant frontotemporal lobe atrophy on cranial MRI. Her dysarthria, dysphagia and the muscle weakness of her extremities worsened, and a muscle biopsy revealed mitochondrial abnormality. The mitochondrial DNA from her muscle showed multiple deletions; the previous physician therefore diagnosed the patient with mitochondrial disease. The patient resembled amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD). No other cases of ALS-FTD with mitochondrial disease have been reported in Japan. We therefore consider the present case to be valuable.
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PMID:[A case of mitochondrial disease with multiple mitochondrial DNA deletions suspected amyotrophic lateral sclerosis-frontotemporal dementia]. 2926 92

We describe a 64-year-old woman, suffering from late-onset obsessive-compulsive disorder (OCD) from the age of 57, who developed dysarthria and dysphagia, spastic diplegic, and proximal muscles weakness. Needle electromyography showed no active denervation. Neuropsychological evaluation showed intact cognitive functioning. We diagnosed upper motor neuron disease (MND), with no known genetic correlates. Brain magnetic resonance (MRI) detected bilateral hippocampal atrophy with sclerosis of right hippocampus. 18F-FDG positron emission tomography (PET) showed moderate right temporal cortex thinning. Six months later, motor and behavioral symptoms worsened. Neuropsychological examination revealed long-term memory deficit and executive dysfunction. MRI and PET evidenced severe worsening of atrophy in temporal and frontal lobes. Four years later a definitive diagnosis of primary lateral sclerosis (PLS) and FTD was made. To our knowledge, this is the first report of PLS and FTD with OCD at onset.
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PMID:A case of late-onset OCD developing PLS and FTD. 2945 Oct 27