原发性进行性失语的临床、影像及语言特征

目的 探讨原发性进行性失语（PPA）的临床、影像及语言特征.方法 PPA患者7例,其中语义性痴呆（SD）6例,进行性非流利性失语（PNFA）1例,收集患者的人口学资料、病史,进行头MRI检查,采用汉语失语成套测验进行语言评估.结果 患者平均发病年龄56岁,均缓慢起病,以语言表达、命名障碍为首发症状.MRI示左侧颞极萎缩为主,病程长的患者左侧额叶和顶叶、右侧颞叶也明显萎缩.语言评估发现所有患者的自发语言、复述、命名、听理解、阅读和书写均不同程度损害.SD患者言语流利,复述、朗读能力下降相对较轻,命名、复杂语句的理解能力损害突出.PNFA言语顿挫吃力,患者列名能力明显下降,但命名相对保存完好.结论 PPA多为老年前期发病,语言障碍为最早、最突出的症状.MRI特征性的改变为额叶和颞极萎缩,左侧为著.其中SD表现为命名性失语和经皮质感觉性失语,PNFA表现为经皮质运动性失语的特征.     

Primary progressive aphasia: a review

This review summarizes clinical and imaging features associated with primary progressive aphasia (PPA). We investigate the hypothesis that these patients can be divided into subgroups of progressive non-fluent aphasia (PNFA) and semantic dementia (SD), based on their linguistic profiles and related imaging studies, and examine whether each of these major subgroups can be further subdivided. We focus on several critical features within each progressive aphasic subgroup. In PNFA, we examine agrammatism, phonologic disorder, and impaired verb processing to determine whether this syndrome is related to a modality-specific impairment in word formation and articulation, or a conceptual deficit that interferes with grammatical processing. In SD, we examine impaired semantic memory, limited remote memory, and anomia to assess whether this syndrome is due to a modality-neutral interruption of semantic memory, or the degradation of various material-specific representations of object features and words. We conclude that there is sufficiently consistent and converging evidence from clinical and imaging studies to support the claim that PNFA and SD are distinct subgroups of PPA. However, there does not appear to be sufficient evidence at this point to support further discrimination within these progressive aphasic subgroups. Testing hypotheses about finer-grained syndromes such as progressive dysarthria or progressive anomia has important consequences for improving our understanding of language organization and the neural basis for language.     

Primary progressive aphasia: diagnosis, varieties, evolution.

A referred cohort of 67 clinically defined PPA patients were compared to 99 AD patients with formal language and nonverbal cognitive tests in a case control design. Language fluency was determined at the first and last follow up visits. Quantitation of sulcal and ventricular atrophy on MRI was carried out in 46 PPA and 53 AD patients. Most PPA patients (57%) are relatively fluent when first examined. Visuospatial and memory functions are initially preserved. Aphemic, stuttering, "pure motor" presentation, or agrammatic aphasia are seen less frequently. Later most PPAs become logopenic and nonfluent, even those with semantic aphasia (dementia). In contrast, AD patients were more fluent and had relatively lower comprehension, but better overall language performance. MRI showed significant left sided atrophy in most PPA patients. Subsequent to PPA, 25 patients developed behavioral manifestations of frontotemporal dementia and 15 the corticobasal degeneration syndrome, indicating the substantial clinical overlap of these conditions. Language testing, particularly fluency scores supported by neuroimaging are helpful differentiating PPA from AD. The fluent-nonfluent dichotomy in PPA is mostly stage related. The aphemic-logopenic-agrammatic and semantic distinction is useful, but the outcomes converge.     

Primary progressive aphasia: a 25-year retrospective

The diagnosis of primary progressive aphasia (PPA) is made in any patient in whom a language impairment (aphasia), caused by a neurodegenerative disease (progressive), constitutes the most salient aspect of the clinical picture (primary). The language impairment can be fluent or nonfluent and may or may not interfere with word comprehension. Memory for recent events is relatively preserved although memory scores obtained in verbally mediated tests may be abnormal. Lesser changes in behavior and object recognition may be present but are not the leading factors that bring the patient to medical attention. This selective clinical pattern is most conspicuous in the initial stages of the disease. Progressive nonfluent aphasia and some types of semantic dementia can be considered subtypes of PPA. Initially brought to the attention of contemporary literature 25 years ago, PPA has recently witnessed substantial progress related to its neurolinguistic features, neuroanatomy, imaging, neuropathology, genetics, and risk factors.     

Cognition and anatomy in three variants of primary progressive aphasia

We performed a comprehensive cognitive, neuroimaging, and genetic study of 31 patients with primary progressive aphasia (PPA), a decline in language functions that remains isolated for at least 2 years. Detailed speech and language evaluation was used to identify three different clinical variants: nonfluent progressive aphasia (NFPA; n = 11), semantic dementia (SD; n = 10), and a third variant termed logopenic progressive aphasia (LPA; n = 10). Voxel-based morphometry (VBM) on MRIs showed that, when all 31 PPA patients were analyzed together, the left perisylvian region and the anterior temporal lobes were atrophied. However, when each clinical variant was considered separately, distinctive patterns emerged: (1) NFPA, characterized by apraxia of speech and deficits in processing complex syntax, was associated with left inferior frontal and insular atrophy; (2) SD, characterized by fluent speech and semantic memory deficits, was associated with anterior temporal damage; and (3) LPA, characterized by slow speech and impaired syntactic comprehension and naming, showed atrophy in the left posterior temporal cortex and inferior parietal lobule. Apolipoprotein E epsilon4 haplotype frequency was 20% in NFPA, 0% in SD, and 67% in LPA. Cognitive, genetic, and anatomical features indicate that different PPA clinical variants may correspond to different underlying pathological processes.     

Is there a schizophasia? A study applying the single case approach to formal thought disorder in schizophrenia

It has been suggested that formal thought disorder, the incoherent speech of schizophrenia, may involve a language disturbance among other abnormalities, or even be a form of dysphasia. Six patients with and seven without formal thought disorder were evaluated on an aphasia test battery. Spontaneous speech was also analysed using Brief Syntactic Analysis. Poor performance on the aphasia test battery was found to be associated with general intellectual impairment but not with formal thought disorder. Naming was preserved in both groups. Patients with formal thought disorder, but not those without, produced semantic errors in their spontaneous speech, and these were unrelated to general intellectual status. The disorder of language in formal thought disorder thus appears to be one of expressive semantic abnormality, which, however, spares naming. Further analysis of two intellectually preserved patients suggested that formal thought disorder may be associated with an additional difficulty in constructing an appropriate model for generating one's own speech.     

A longitudinal study of sentence comprehension difficulty in primary progressive aphasia

CONTEXT: Patients with primary progressive aphasia have sentence comprehension difficulty, but the longitudinal course of this deficit has not been investigated. OBJECTIVE: To determine how grammatical, single word meaning, and working memory factors contribute to longitudinal decline of sentence comprehension in primary progressive aphasia. We hypothesised partially distinct patterns of sentence comprehension difficulty in subgroups of patients with progressive non-fluent aphasia (PNFA) and semantic dementia (SD). DESIGN: Cohort. SETTING: Institutional out patient referral centre. PATIENTS: PNFA (n = 14), SD (n = 10). MAIN OUTCOME MEASURE: Sentence comprehension accuracy. RESULTS: PNFA patients were significantly impaired at understanding grammatically complex sentences when first seen, and this was more evident than impairment of their comprehension of grammatically simple sentences (p<0.05). Comprehension of grammatically complex sentences correlated with their working memory deficit at presentation (p<0.05). PNFA patients showed modest decline over time in grammatical comprehension. In SD, comprehension of grammatically complex sentences was not more impaired than comprehension of grammatically simple sentences when first seen, but these patients demonstrated a significant longitudinal decline in understanding grammatically complex sentences (p<0.05). Cox regression analyses showed that a deficit in single word meaning contributes to the progressive impairment for grammatically complex sentences in SD (p<0.05), but working memory does not contribute to longitudinal decline in PNFA. CONCLUSION: Patients with PNFA and SD have sentence comprehension difficulty, but distinct factors contribute to this impairment during the course of their disease.     

Repeat and Point: differentiating semantic dementia from progressive non-fluent aphasia

To determine whether a new, simple, quick measure, the Repeat and Point test, reliably differentiates between semantic dementia (SD) and progressive non-fluent aphasia (PNFA). Fifteen patients with SD, six patients with PNFA and 18 healthy controls were administered the Repeat and Point test. Participants were required to repeat 10 multi-syllabic concrete nouns and, following each repetition, to point to the word's pictorial referent amongst an array of six semantically and perceptually similar foils. Patients with SD were consistently impaired relative to PNFA patients and controls on the comprehension (pointing) component of the task, whereas patients with PNFA showed no significant deficit on pointing but were impaired at the production (repeating) component. Discriminant function analysis confirmed perfect classification of the individual patients into their respective groups: criteria involving a ratio of the two scores are provided. The Repeat and Point test is particularly appropriate for routine use in a clinical context: it is quick and easy to administer and score; it reliably discriminated between the two patient groups, SD and PNFA; and it offers a simple rule of thumb, i.e., the Repeat-to-Point ratio, to aid in the diagnosis of these two language variants of frontotemporal dementia (FTD).     

Creutzfeldt-Jakob disease revealed by a logopenic variant of primary progressive aphasia

Logopenic aphasia, mainly characterized by word anomia, sentence and phrase comprehension difficulties secondary to phonological loop deficits but relatively preserved single word comprehension and no agrammatism, is one of the 3 main variants of primary progressive aphasia (PPA). We describe the first case of PPA that fulfilled clinical criteria of logopenic aphasia but showed abnormal DWI hyperintensities that were predominant on the left hemisphere and compatible with Creutzfeldt-Jakob disease (CJD). After abnormally long isolated language deficits, the patient rapidly worsened and died. Autopsy performed 18 months after onset of language difficulties confirmed the diagnosis. We therefore advocate performing DWI sequences in any suspicion of PPA in order to rule out CJD.     

Mixed language dominance: insights from a case of unexpected fluent aphasia with semantic jargon resulting from massive left perisylvian lesion

We report a right-handed patient with a massive lesion in left perisylvian language cortex, who unexpectedly presented with fluent aphasia with semantic jargon. Language deficits were assessed with a comprehensive battery of language tests. Comprehension, naming, reading, and writing were severely impaired, and verbal expression was moderately fluent with semantic jargon. Although the patient’s lesion included brain areas typically essential for motor speech coordination, he was neither nonfluent nor apraxic. He exhibited strikingly unexpected aphasia with semantic jargon and prominent comprehension deficits, suggesting that this is a case of mixed dominance: the right hemisphere likely controls motor speech and basic syntactic skills, while the severely damaged left hemisphere controls semantic processing, predictably severely impaired.     

Primary progressive aphasia

Primary progressive aphasia (PPA) is a focal dementia characterized by an isolated and gradual dissolution of language function. The disease starts with word-finding disturbances (anomia) and frequently proceeds to impair the grammatical structure (syntax) and comprehension (semantics) of language. The speech output in PPA can be fluent or nonfluent. Memory, visual processing, and personality remain relatively well-preserved until the advanced stages and help to distiguish PPA from frontal lobe dementia and the typical forms of Alzheimer's disease. The term "semantic dementia" was originally introduced to designate a different group of patients with a combination of verbal and visual processing deficits. In practice, however, this diagnosis is also being used in a variant sense to denote a subtype of PPA with fluent speech and impaired comprehension, even in the absence of visual processing deficits. Insofar as the diagnosis of semantic dementia can have these two different meanings, it is important to specify whether it is being used in the original sense or to denote a subtype of PPA. Structural and physiological neuroimaging confirms the selective predilection of PPA for the left hemisphere, especially for its language-related cortices. A few patients with PPA display the neuropathological markers of Alzheimer's disease, but in an unusual distribution. The majority of the autopsies in PPA have shown either Pick's disease or lobar atrophy without distinctive histopathology. The suggestion has been made that PPA and frontal lobe dementia constitute phenotypical variations of a unitary disease process within the "Pick-lobar atrophy" spectrum. Recent advances in chromosome 17-linked dementias justify a rigorous search for tau polymorphisms and tauopathy in sporadic PPA. An informed approach to this syndrome will increase the effectiveness with which clinicians can address the unique challenges associated with the diagnosis and care of PPA.     

The time course of neurolinguistic and neuropsychological symptoms in three cases of logopenic primary progressive aphasia

Primary progressive aphasia (PPA) is a rare clinical dementia syndrome affecting predominantly language abilities. Word-finding difficulties and comprehension deficits despite relatively preserved cognitive functions are characteristic symptoms during the first two years, and distinguish PPA from other dementia types like Alzheimer's disease. However, the dynamics of changes in language and non-linguistic abilities are not well understood. Most studies on progression used cross-sectional designs, which provide only limited insight into the course of the disease. Here we report the results of a longitudinal study in three cases of logopenic PPA over a period of 18 months, with exemplary longitudinal data from one patient even over 46 months. A comprehensive battery of neurolinguistic and neuropsychological tests was applied four times at intervals of six months. Over this period, deterioration of verbal abilities such as picture naming, story retelling, and semantic word recall was found, and the individual decline was quantified and compared between the three patients. Furthermore, decrease in non-verbal skills such as divided attention and increasing apraxia was observed in all three patients. In addition, inter-subject variability in the progression with different focuses was observed, with one patient developing a non-fluent PPA variant. The longitudinal, multivariate investigation of logopenic PPA thus provides novel insights into the progressive deterioration of verbal as well as non-verbal abilities. These deficits may further interact and thus form a multi-causal basis for the patients' problems in every-day life which need to be considered when planning individually targeted intervention in PPA.     

Corticobasal degeneration presenting with progressive conduction aphasia

We report the case of a woman with primary progressive aphasia (PPA) presenting with conduction aphasia. Neurological findings showed bilateral finger tremor and signe de poignet figé in her right hand. Memory, orientation, and activities of daily living were well preserved. Linguistic examination showed severe impairment in repetition, fluent spontaneous speech with phonemic paraphasia, and relatively well preserved comprehension. Limb-kinetic apraxia and parkinsonism were not observed during the course of her illness. T1-weighted magnetic resonance imaging revealed severe atrophy of the left temporal lobe and dilatation of the left Sylvian fissure. Neuropathological findings demonstrated the most severe atrophy in the left superior temporal gyrus and Gallyas–Braak-positive or phosphorylated tau-immunoreactive cytoskeletal structures, which were consistent with corticobasal degeneration (CBD). We speculate that the progressive conduction aphasia of our patient might have been caused by left temporal lobe impairment. We suggest that progressive conduction aphasia may be a feature of CBD presenting with PPA.     

Emergence of artistic talent in progressive nonfluent aphasia: a case report

Some patients with frontotemporal lobar degeneration have developed artistic skills after the onset mainly in painting and music. Most of these cases have semantic dementia (SD), one of the frontotemporal lobar degeneration subtypes. In previously reported cases, the paintings made by patients with SD were usually hyper realistic, without a significant symbolic or abstract component. Here, we report on a patient with progressive nonfluent aphasia (PNFA), another frontotemporal lobar degeneration subtype, who started making creative bamboo crafts after PNFA onset. His techniques were completely his original; he devised the shapes of the crafts and made them without samples. His work did not become an obsessive preoccupation. The artistic style expressed by patients with PNFA differs from that expressed by patients with SD. Therefore, the underlying mechanisms for the emergence of artistic talent might differ between SD and PNFA.     

Therapy for naming deficits in two variants of primary progressive aphasia

Background: Primary progressive aphasia (PPA) refers to a progressive and selective decline in language due to neurodegenerative disease. There are three variants of PPA, progressive nonfluent aphasia (PNFA), semantic dementia (SD), and logopaenic progressive aphasia (LPA). All variants include impaired object naming, but distinct underlying deficits might interfere with naming. Therefore, individuals with different types of PPA may respond differently to naming therapy.

Aims: To identify differences in patterns of success and generalisation in response to the same treatment in patient with LPA and a patient with SD. Furthermore, we wished to identify whether the treatment effect was item specific (trained words) or generalised to untrained words in trained or untrained categories.

Methods & Procedures: Participants included an individual with LPA and one with SD. An assessment of lexical processing was administered before and after a naming treatment to assess underlying deficits and generalisation effects. Therapy consisted of a cueing hierarchy treatment. Treatment items consisted of pictured objects in the categories of fruits/vegetables and clothing.

Outcomes & Results: Two different patterns of performance were observed. The LPA participant improved in naming of treated items and untreated items in both treated and untreated categories. The participant with SD improved in naming treated items only, but showed less deterioration in untreated items in treated than untreated categories.

Conclusions: Individuals with PPA can show improved naming (at least temporarily) with therapy, but generalisation to untrained items may depend on the underlying cause of the naming deficit, which may differ across subtypes.     

Primary progressive aphasia presenting as conduction aphasia.

We report a case of a woman with primary progressive aphasia (PPA) who presented with conduction aphasia. A 60-year-old, right-handed, Japanese female suffering from progressive aphasia had difficulty in repeating words and phrases. She displayed phonemic paraphasias but had preserved comprehension and had no cognitive or behavior disorder for more than 6 years after the onset of the condition. She was able to continue to work successfully and to perform all her normal daily activities. T1-weighted magnetic resonance imaging revealed minute dilatation of the left inferior horn and sulci in the left hemisphere, and positron emission tomography revealed mild hypometabolism in the left supramarginal gyrus and its surrounding areas. Therefore, she was diagnosed as suffering from PPA presenting as conduction aphasia. We believe that the progressive conduction aphasia of the patient belongs to one of the fluent forms of PPA, and the ability to continue normal work along with the clinical portrayal of preserved memory and cognition skills may be features of a form of PPA presenting as conduction aphasia.     

Atypical progressive supranuclear palsy underlying progressive apraxia of speech and nonfluent aphasia

Progressive supranuclear palsy (PSP) is a clinicopathological entity typically presenting as an akinetic rigid syndrome with early falls, axial rigidity, vertical supranuclear gaze palsy and levodopa resistance. Pathological features consist of tau deposition in neuronal and glial cells located mainly in subcortical and brainstem structures. Rare cases with the pathological diagnosis of atypical PSP have been described in which neocortical tau deposition is more widespread than what is usually seen in typical PSP. Progressive nonfluent aphasia (PNFA) is a syndrome characterized by spontaneous nonfluent speech and early preserved comprehension of language. Apraxia of speech (AOS) is a motor speech disorder that may be a feature of PNFA. We report the clinical and pathological findings of four cases that presented with features most consistent with PNFA predominated by AOS. Pathological features in these four cases included the typical features of PSP subcortically and in brainstem structures, but combined with tau-positive neuronal and glial pathology in the neocortex. Comprehensive semiquantitative analyses of tau burden including neurofibrillary tangles and pretangles, coiled bodies, tufted astrocytes and threads were undertaken in the four cases of atypical PSP and compared to 10 cases of typical PSP. Semiquantitative analysis demonstrated that in atypical PSP, the pathology shifts from subcortical grey and brainstem regions, commonly affected in typical PSP, towards neocortical regions. This shift in pathology accounts for the presentation of PNFA and AOS observed in our patients, as well as the lack of classic features of PSP. These cases demonstrate that atypical PSP can present as AOS and PNFA without the classic features of PSP.     

Semantic dementia and primary progressive aphasia: a problem of categorization?

The relationship between semantic dementia (SD) and primary progressive aphasia (PPA) has been the subject of debate ever since the syndromes were first described, in converging streams of research from the neuropsychological and neurologic communities. The most salient clinical features of SD are anomia with circumlocution and semantic paraphasia, single-word comprehension deficit, and reduced category fluency. Of critical importance is the fact that patients also show deficits on non-verbal tasks using visual, auditory, and other modalities, suggesting that the key impairment in SD is a breakdown in conceptual knowledge rather than a specific problem with language. The finding of item consistency between the various tests supports this view. The order in which the features appear can be explained by the variable degree of redundancy in access to semantic knowledge from the different perceptual modalities. Atrophy is seen in the anterior and inferior temporal lobe rather than in classic language areas, further distancing SD from aphasic syndromes. Semantic dementia and progressive non-fluent aphasia (PNFA) share some clinical and pathologic characteristics with frontal variant frontotemporal dementia, but there are also clear differences between the three syndromes. We believe that many patients described as having fluent primary progressive aphasia in fact have early SD. Semantic dementia is a well-defined syndrome, distinct from PNFA but related to it within the spectrum of frontotemporal lobar degeneration syndromes.