Word-Finding Difficulty: A Clinical Analysis of the Progressive Aphasias

Jonathan D. Rohrer; William D. Knight; Jane E. Warren; Nick C. Fox; Martin N. Rossor; Jason D. Warren


Brain. 2008;131(1):8-38. 

In This Article

Summary and Introduction

The patient with word-finding difficulty presents a common and challenging clinical problem. The complaint of 'word-finding difficulty' covers a wide range of clinical phenomena and may signify any of a number of distinct pathophysiological processes. Although it occurs in a variety of clinical contexts, word-finding difficulty generally presents a diagnostic conundrum when it occurs as a leading or apparently isolated symptom, most often as the harbinger of degenerative disease: the progressive aphasias. Recent advances in the neurobiology of the focal, language-based dementias have transformed our understanding of these processes and the ways in which they breakdown in different diseases, but translation of this knowledge to the bedside is far from straightforward. Speech and language disturbances in the dementias present unique diagnostic and conceptual problems that are not fully captured by classical models derived from the study of vascular and other acute focal brain lesions. This has led to a reformulation of our understanding of how language is organized in the brain. In this review we seek to provide the clinical neurologist with a practical and theoretical bridge between the patient presenting with word-finding difficulty in the clinic and the evidence of the brain sciences. We delineate key illustrative speech and language syndromes in the degenerative dementias, compare these syndromes with the syndromes of acute brain damage, and indicate how the clinical syndromes relate to emerging neurolinguistic, neuroanatomical and neurobiological insights. We propose a conceptual framework for the analysis of word-finding difficulty, in order both better to define the patient's complaint and its differential diagnosis for the clinician and to identify unresolved issues as a stimulus to future work.

'Word-finding difficulty' is a common and challenging problem in neurological practice. In many cases, patients will complain of word-finding difficulty or, not uncommonly, the difficulty is identified by the neurologist in the course of the assessment. In both situations, the basis for the word-finding problem needs to be established but this is often not straightforward. Spoken communication depends on a sequence of cognitive processes, and disruption of any of these processes can affect word-finding (Fig. 1). Furthermore, processing occurs in a distributed network of brain areas that is vulnerable to a variety of acute and chronic pathological states (Levelt, 1989; Price et al., 1993; Levelt, 2001; Blank et al., 2002; Gorno-Tempini et al., 2004). The differential diagnosis of word-finding difficulty therefore encompasses a wide spectrum of acute and chronic disorders as diverse as delirium (Geschwind, 1964), aphasic stroke (Kertesz and McCabe, 1977), encephalitis (Okuda et al., 2001), major depression (Georgieff et al., 1998) and psychosis (Critchley, 1964), head injury (Levin et al., 1976), temporal lobectomy (Langfitt and Rausch, 1996) and metabolic and genetic disorders (Spinelli et al., 1995). In particular, however, it is a leading symptom of a number of degenerative conditions: the progressive aphasias (Mesulam, 1982, Hodges et al., 1992; Mesulam, 2003; Gorno-Tempini et al., 2004). In the degenerative diseases, in contrast to many of the other conditions associated with word-finding difficulty, the cause of the word-finding problem may not be obvious or it may be the presenting complaint: accurate diagnosis therefore depends on detailed characterization of the language deficit. It is accordingly in the context of degenerative disease that word-finding difficulty usually presents the greatest diagnostic challenge, yet the classical approach to the clinical assessment of language (which is based largely on the accumulated experience of aphasia in acute stroke: Hillis, 2007) may not be adequate. This reflects the often unique problems posed by speech and language breakdown in the degenerative dementias (Warrington, 1975; Mesulam, 2003).

An outline of clinical syndromes and underlying functional deficits in patients with word-finding difficulty. Relations between acute and chronic syndromes and primary and secondary functional deficits are shown. Numerals refer to the operational stages in the language output pathway (dotted lines indicate processes that are related to but not essential for language output): I = generation of a verbal message; II = sense of the verbal message; III = structure of the verbal message; IV = motor programming of speech. Key: esp = especially; HSV = Herpes simplex encephalitis.

Here we use 'word-finding difficulty' as a shorthand for a class of symptoms which patients and carers commonly volunteer when describing impaired language output. Progressive cognitive syndromes with circumscribed deficits and preserved intellect have been recognized for many years (for example, Pick, 1892; Serieux, 1893, see also Luzzatti and Poeck, 1991; De Bleser, 2006 for other historical cases) and may preferentially affect a variety of cognitive domains, however the comparatively recent renaissance of interest in the language-based dementias (Mesulam, 1982) has transformed our picture both of disease biology in neurodegeneration and the organization of the human language system. The focal dementias pose considerable nosological and neurobiological difficulties. While circumscribed atrophy on structural brain imaging can support the impression of a focal dementia, diagnosis remains essentially clinical. Primary progressive aphasia (PPA) is a clinical syndrome of progressive language impairment with relative sparing of other aspects of cognitive function until late in the course (Mesulam, 1982, 2001, 2003). This broad definition subsumes substantial clinical, anatomical and pathological heterogeneity, and a spectrum of clinical subtypes of PPA has been described. While these subtypes have more or less distinctive profiles of speech and language disturbance, even where clinical characterization is robust (for example, in the distinction between 'fluent' and 'non-fluent' forms of PPA) understanding of the underlying pathophysiological mechanisms remains limited (Mesulam and Weintraub, 1992; Grossmann, 2002; Mesulam et al., 2003) Moreover, the overlap between clinical subtypes is substantial, incomplete syndromes are frequent (Grossmann, 2002; Mesulam et al., 2003), and none has been shown to have a unique correspondence with either anatomy or tissue pathology. This presents serious and unresolved nosological difficulties, and for the clinician, a substantial diagnostic dilemma. Furthermore, the stimulus of the focal language-based dementias has led to a wider appreciation of speech and language dysfunction in other neurodegenerative conditions, including Alzheimer's disease (AD) (Emery, 2000; Croot et al., 2000) and the problem of the differential diagnosis of 'progressive aphasia' in this broader sense. Accordingly, a conceptual framework is needed to allow the clinician to interpret the patient's complaint of word-finding difficulty in line with emerging evidence for language network dysfunction in neurodegenerative diseases.

Here we outline such a framework for the clinical analysis of 'word-finding difficulty'. We propose a clinical scheme that can be used at the bedside to categorize the nature of the problem and to formulate a differential diagnosis, with reference in particular to the degenerative dementias, presented in Fig. 2. This scheme has speech as its focus because word-finding difficulty in spoken language is generally the dominant complaint in the progressive aphasias. Our scheme is informed by evidence emerging from the experimental brain sciences, and contemporary information-processing accounts of language processing (Levelt, 1989; Warren and Warrington, 2007; Hillis, 2007) (Fig. 1). Application of the scheme generates a taxonomy of clinical syndromes arising from different operational stages in the language output pathway and with distinct anatomical substrates. Our approach is based on a series of steps that probe the key stages in language output (Fig. 1). These steps are elaborated in the following sections and in Table 1 , Table 2 , Table 3 , Table 4 . The pattern of performance at each step identifies the cognitive processing stage that is principally affected and builds up a detailed profile of the speech syndrome. Both these levels of analysis are of clinical relevance: the broad cognitive operational level allows the deficit to be localized (Fig. 3), while the detailed syndromic description guides the differential diagnosis of the likely pathological process (Fig. 2). Our intention is to provide the neurologist with a bridge between the dilemmas of the bedside and the theoretical constructs of the brain sciences, rather than a comprehensive neurolinguistic treatise on the progressive aphasias. At the same time, however, we hope to show that understanding of the pathophysiology of these diseases can be advanced by the characterization of clinical phenomena that are difficult to reconcile with theoretical models of language function and dysfunction.

A clinical scheme for assessing the patient with word-finding difficulty, particularly in the context of degenerative disease. The scheme is organized as a 'grid' in which each column represents a key step in the clinical assessment, and each row represents a speech or language syndrome. Each entry in the grid represents an abnormality. Based on the initial assessment of features of the patient's spontaneous speech directed toward key language operations (left; see also Fig. 1), followed by key speech and language tasks (centre), the clinical speech or language syndrome is characterized. Identification of the clinical syndrome allows a differential diagnosis to be formulated, based on associated clinical features (right) including both cognitive and other neurological abnormalities. These associated features also allow primary and secondary effects on word-finding to be interpreted (Fig. 1). See text for details. Key: filled circle = abnormal; AOS = apraxia of speech; * = as used in consensus criteria; = nosological status not established; AD = Alzheimer's disease; bvFTLD = behavioural variant of frontotemporal lobar degeneration; CBD = corticobasal degeneration syndrome; CIRCUMLOC = empty, circumlocutory speech; COG = cognitive features; EPS = extrapyramidal syndrome; LTPS = lateral temporo-parietal syndrome; MND = motor neuron disease; PNFA = progressive nonfluent aphasia; PSP = progressive supranuclear palsy; SD = semantic dementia; SURFACE = surface (regularization) errors; VaD = vascular dementia.

Structural anatomy of word-finding difficulty in degenerative disorders. Numerals and connecting arrows refer to the operational stages in the language output pathway (coded in Fig. 1 and Table 2 ). Key anatomical areas are indicated. Arrows are bi-directional to indicate that flow of information between these areas is likely to be reciprocal. Brain magnetic resonance images illustrate some degenerative disorders with word-finding difficulty (the left hemisphere is on the right side in all coronal sections; TL = temporal lobe): (a) asymmetric (left greater than right) frontal lobe atrophy, dynamic aphasia; (b) focal left anterior/inferior temporal lobe atrophy, semantic dementia; (c) bilateral mesial temporal atrophy, Alzheimer's disease (anomia); (d) left posterior superior temporal/inferior parietal atrophy, progressive 'mixed', logopenic or jargon aphasia; (e) focal left superior temporal lobe/insular atrophy, progressive nonfluent aphasia; (f) focal left inferior frontal gyrus/frontal opercular atrophy, progressive apraxia of speech.


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