Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003635 (apraxia)
 2,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the case of a 76-year-old man with apraxia of eyelid opening (AEO) and amyotrophic lateral sclerosis with dementia (ALS-D)/frontotemporal lobar degeneration with motor neuron disease (FTLD-MND). The initial symptom was AEO. Neurological examination revealed mainly bulbar symptoms with a neurogenic pattern on needle electromyograms of the tongue muscles and the biceps muscles. Furthermore, he developed severe dementia with frontal lobe dysfunction and progressive non-fluent aphasia. Brain magnetic resonance imaging revealed severe cerebral atrophy and leukoaraiosis in the bilateral frontal lobes and the anterior part of the bilateral temporal lobes; brain 99mTc ethyl cysteinate dimer single photon emission computed tomography (ECD SPECT) showed hypoperfusion in the same areas. The patient showed improvement in stereotyped behavior and AEO after treatment with 50 mg/day of fluvoxamine maleate (the initial dose was 25 mg/day). Because serotonin receptors are markedly reduced in the frontal and temporal cortexes of patients with FTLD, we considered that dysfunction of the serotonergic system in the frontotemporal lobe caused AEO. Considering the findings of this case along with those of previous reports, we propose that there is a relatively homogeneous development of ALS-D/FTLD-MND with AEO.
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PMID:[A case of amyotrophic lateral sclerosis/frontotemporal lobar degeneration with apraxia of eyelid opening]. 2096 Sep 30

Descriptions of extrapyramidal (EP) involvement in Pick's disease (renamed recently as FTD) appeared 80 years ago. CBD pathology was confirmed as a common substrate for primary progressive aphasia (PPA). We suggested that CBD and PPA should be included with frontal lobe dementia as Pick complex. PSP was prototype for "subcortical dementia", and aphasia and apraxia, considered unusual for PSP, are now seen as a rule. The overlap of PSP and CBD is considerable. We recently reviewed our cohort with EPS in FTD and identified 22 patients with the movement disorder as a first syndrome and another larger group of 48 patients who developed EPS after an initial onset with a cognitive disorder: aphasic, behavioral or both. All cognitive onset CBD/PSP patients and all but two with motor onset developed aphasia during the course of their illness. General cognitive and behavioral measures are similar for each presentation, but language scores are worse in cognitive onset cases, reflecting the frequency of aphasic presentations. Anomic patients become non-fluent, logopenic, agrammatic and mute. Using the Frontal Behavioral Inventory (FBI), a questionnaire specifically designed for the spectrum of apathy and disinhibition displayed by patients with FTD, we have documented the behavior change in CBD/PSP with motor and cognitive onsets. The significant personality changes consisted of apathy, disinhibition, perseveration and inattention, some of the core symptoms of FTD. In 18 autopsied cases, 15 had tau pathology. The overlap of CBD/PSP with PPA and bvFTD suggests a spectrum of related entities and predicts tau-positive pathology. Cross-sectional studies without significant follow-up may not observe the subsequent development language or behavior deficit, or the evolution from PPA and/or FTD-bv to CBD/PSP.
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PMID:Extrapyramidal syndromes in frontotemporal degeneration. 2188 21

Frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP) and Pick's disease are common pathological substrates in FTLD patients. Because most Japanese FTLD-TDP patients lack a family history, characterizing clinical features in sporadic FTLD-TDP is important to infer the underlying pathologies in FTLD patients. Our recent study suggested that these two diseases tended to show different clinical pictures. Early impairment of semantic memory was frequent in sporadic FTLD-TDP, but very rare in Pick's disease. In contrast, early impairment of speech output, including non-fluent aphasia and speech apraxia, was more frequent in Pick's disease. Asymmetric motor disturbances (e.g., pyramidal signs, parkinsonism, and contracture) were frequent in sporadic FTLD-TDP, but rare in Pick's disease. The most common first syndrome in FTLD-TDP was semantic dementia (39%), but that in Pick's disease was frontotemporal dementia (64%). Pathologically, consistent with clinical features, the temporal cortex, striatum, globus pallidus, substantia nigra, and pyramidal tract were more severely degenerated in sporadic FTLD-TDP. These findings suggest that the early impairment of semantic memory and asymmetric motor disturbances in sporadic FTLD patients predict FTLD-TDP rather than Pick's disease, while initial behavioral symptoms or non-fluent aphasia without subsequent asymmetric motor disturbances predict Pick's disease rather than FTLD-TDP.
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PMID:[Clinicopathological features of sporadic frontotemporal lobar degeneration with TDP-43-positive inclusions]. 2192 51

This review focuses on six key papers published in the mid 2000 s based on work conducted in Cambridge. The first two relate to clinico-pathological studies which established that Alzheimer's disease (AD) is a relatively common cause of focal cortical syndromes, notably progressive aphasia (largely nonfluent), progressive apraxia, and posterior cortical atrophy with complex visual symptoms. Building on these findings, criteria for the progressive aphasias have been developed which define the variant associated with AD (progressive logopenic aphasia). Memory in the dementias has been a major area of interest and one paper discussed here explored the neural basis for episodic and semantic memory failure in AD and semantic dementia. Despite very different memory profiles, the two disorders both cause severe hippocampal hypometabolism and atrophy but differ in the degree of involvement of other memory related structures. This work drew attention to the role of pathology in non-hippocampal structures early in AD. The next two articles deal with the behavioral variant frontotemporal dementia (bvFTD) which we have shown is associated with breakdown in theory of mind, social reasoning, empathy, and emotion processing and contributed towork on the neural basis of social cognition. We also identified a subgroup of bvFTD who fail to progress over many years, termed phenocopy cases, who are differentiated by their lack of atrophy on MRI. The final paper described the application of the Addenbrooke's Cognitive Examination-Revised, which has proven a useful brief assessment tool for the early detection of a range of neurodegenerative disorders including AD and FTD. It also appears to be helpful in predicting those with mild cognitive impairment who will progress to frank dementia.
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PMID:Alzheimer's disease and the frontotemporal dementias: contributions to clinico-pathological studies, diagnosis, and cognitive neuroscience. 2276 37

FTLD consists of three clinical types: behavioural variant FTD, progressive non-fluent aphasia (PNFA) and semantic dementia (SD). The latter two types manifest aphasia. Thus, it is quite important to pertinently assess the symptoms of aphasia and related impairments for diagnosis of FTLD. The most important point for diagnosis of PNFA is existence of anarthria/apraxia of speech, which is a focal symptom of the left prefrontal gyrus and underlying white matter. With the progression of the disease word generation and comprehension is deteriorating. SD shows Gogi aphasia when the lesion have predilection of left temporal lober atrophy. We investigated 28 patients without any antecedents causing speech/language impairments, who developed primary progressive aphasia. All the patients underwent a routine neurological and neuropsychological examinations and related symptoms such as orofacial apraxia, frontal lobe signs, dysphasia and so on were assessed. The results indicated that 20 patients were diagnosed as PNFA, and they were subdivided into three clinical groups. One group developed naming impairment and orofacial apraxia in several years after onset, and followed with various frontal symptoms. Another group showed anterior opereculum syndromes within two years after onset. The third group retained pure anarthria/apraxia of speech for many years without any other symptoms.
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PMID:[Aphasia and related impairments pertaining to FTLD]. 2319 71

Corticobasal syndrome (CBS) is a clinical syndrome presenting with progressive asymmetric bradykinesia, rigidity, and dystonia accompanied by cortical signs, such as apraxia, alien limb phenomena, cortical sensory loss, myoclonus, and mirror movements. CBS is associated with different pathological conditions including FTLD-tau (corticobasal degeneration, CBD; progressive supranuclear palsy, PSP: and Pick disease), FTLD-TDP, Alzheimer disease, Creutzfeldt-Jakob disease, and Parkinson disease/dementia with Lewy bodies. Among these, the most common pathology is CBD. In patients with familial and sporadic FTLD, MAPT, GRN and C9orf72 mutations are the three main causes of the disease, even though the C9orf72 mutation is rare in Japan. Patients with MAPT mutations present with FTLD-tau, and patients with GRN and C9orf72 mutations exhibit FTLD-TDP. FTLD is also associated with VCP, CHMP2B, TARDBP and FUS mutations, but each of these account for <1% of familial FTLD cases. In sporadic cases, the H1c haplotype and the rare p.A152T variant of MAPT are known to be associated with FTLD-tau, and the common genetic variant (rs5848) in the 3'-UTR of GRN is associated with FTLD-TDP. A recent genome-wide association study identified TMEM106B as a potential risk-modifying factor for FTLD-TDP, and STX6, EIF2AK3 and MOBP, for PSP. Despite major advances in genetic studies in recent years, the majority of sporadic CBS cases are genetically unsolved. Further studies are needed to unveil the genetic background of CBS. In this review, we discuss the recent advances related to the genetics of CBS, particularly about the genetics of FTLD.
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PMID:[The genetics of corticobasal syndrome]. 2330 Jan

Primary progressive aphasia (PPA) is a progressive loss of specific language functions with relative sparing of other cognitive domains at least for the first few years of the illness. Based on the constellation of symptoms, PPA has been recently classified into a nonfluent, semantic, or logopenic variant. Nonfluent variant PPA is characterized by dysfluent and effortful speech, often combined with agrammatism. Also, some patients have initially predominant apraxia of speech. The neuroimaging findings in nfvPPA are in most cases progressive atrophy within the left inferior, opercular, and insular regions. Pathology is a tauopathy (FTLD-T), most often Pick's disease or CBD. Semantic variant PPA, on the other hand is characterized by fluent, but circumlocutory speech, then severe anomia and word-finding difficulties, all being associated with a progressive loss of lexical-semantic knowledge. As the disease progresses, the semantic impairment typically becomes multimodal. The clinical picture of svPPA is often associated with atrophy of the anterior regions of the temporal lobes, usually more prominent on the left side. The majority of these patients have TDP-43 pathology. The third, most recently described form of PPA is the logopenic variant characterized by decreased spontaneous speech output with frequent word-finding pauses, phonologic parahpasias, and repetition deficits. It resembles aphasia in Alzheimer's disease. Imaging abnormalities in lvPPA have been predominantly found in the left temporo-parietal junction area, and the pathological changes have been often those of AD.
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PMID:Primary progressive aphasia. 2471 49

In our study we analysed clinical and neuropsychological data in a cohort of 57 Sardinian patients with FTD (55 apparently unrelated and two belonging to the same family), who underwent genetic screening for the C9orf72 mutation. Eight out of 56 patients were found positive for the C9orf72 mutation representing 14% of the entire cohort and 31.6% of the familial cases (6/19). C9orf72 mutated patients differed from the other FTD cases of the cohort for a younger age of onset, higher frequency of familial history for FTD and higher prevalence of delusional psychotic symptoms and hallucinations. In the neuropsychological assessment, C9orf72 mutated patients differed from non-mutated for the high frequency of visuospatial dysfunction regarding constructional apraxia (p = 0.02). In conclusion, our study confirms that Sardinian FTD patients have peculiar genetic characteristics and that C9orf72 mutated patients have a distinctive clinical and neuropsychological profile that could help differentiate them from other FTD patients. In our cohort we found that constructional apraxia, rarely reported in FTD, can properly discriminate between C9orf72 mutated and non-mutated patients and contribute to broaden the neuropsychological profile in frontotemporal dementia associated with this mutation.
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PMID:Constructional apraxia in frontotemporal dementia associated with the C9orf72 mutation: broadening the clinical and neuropsychological phenotype. 2528 76