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Agraphia


Agraphia

Article Author:
Jonathan Tiu
Article Editor:
Alex Carter
Updated:
7/15/2020 1:30:10 AM
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Agraphia

Introduction

Agraphia is an impairment or loss of a previous ability to write. Agraphia can occur in isolation, although it often occurs concurrently with other neurologic deficits such as alexia, apraxia, or hemispatial neglect. Clinically, agraphia can be divided into “central” agraphia (also called “linguistic” or “aphasic“ agraphia), and “peripheral” agraphia (also called “nonlinguistic” or “nonaphasic” agraphia).[1]

To perform the act of writing, an individual produces a series of “graphemes” to communicate meaningful information. In the English language, graphemes consist of the letters of the Latin alphabet. To write properly, one must first have knowledge of the letters themselves, and then one must know how to organize letters to form proper words and grammatically correct sentences. Lesions disrupting these processes result in central agraphia. The individual must then have the knowledge of the set of coordinated movements to correctly draw out letters (praxis), the ability to “mentally queue up” a sequence of letters to make an entire word (motor programming), the visuospatial ability to guide a writing implement on a writing surface, and finally, the motor system to carry out these tasks.[1][2] Impairment of these latter steps involved in the motor planning or motor action of writing leads to peripheral agraphia. Note that “peripheral” agraphia can localize to the central nervous system when it does not directly involve linguistic centers, such as in the case of motor agraphia due to a motor cortex lesion leading to the paresis of the writing limb.

There exist both clinical neurologic and neuropsychological classification schema to categorize the agraphias, and a clinical neurologic classification is used in this review. “Pure agraphia” is a term that is used to refer to an isolated impairment of writing without an associated relevant impairment in either language ability or praxis. While certain authors equate “pure agraphia” with apraxic agraphia, there is an effort by other authors to distinguish between “pure linguistic (or aphasic) agraphia” and “pure apraxic agraphia”.[3] This review agrees with making this distinction on both a clinical and anatomic basis, and the evidence for supporting this distinction is discussed throughout this article.
It must also be noted that the term “aphasia” is used inconsistently in literature. Aphasia most commonly refers to an acquired impairment of just spoken language, but it is also frequently used to encompass impairments of both written and spoken language.[2][4][5] 

This article uses the term “aphasia” to refer to an isolated impairment of spoken language. The peripheral agraphias can be viewed as analogous to “dysarthrias” of written language, in the sense that “dysarthria” denotes an impairment in the motor output of verbal language. Furthermore, in central agraphia, it possible for there to be a dissociation between written and spoken language ability; in some cases, there is even a difference in the type of aphasia manifested in the same patient, such as verbal nonfluent aphasia accompanied by written fluent aphasia.[6][7] The qualifier term “linguistic” is used in this review to encompass issues of both written and spoken language.

Agraphia is distinguished from illiteracy, in which case the ability to write is never obtained. The term “dysgraphia” is used most commonly to denote handwriting impairment as part of a primary learning disability, but it is also sometimes used to denote an incomplete acquired writing impairment and, in this case, is synonymous with agraphia.[8] “Paragraphia” refers to a specific writing error, and they are analogous to the paraphasic errors of speech. The impairment of typing on a keyboard—dystypia, or dystextia in the case of mobile phone use--often accompanies agraphia, but cases of isolated dystypia or dystextia suggest these may represent distinct impairments.[9]

  • Central (Linguistic) Agraphia
    • Agraphia with Nonfluent Aphasia
      • Agraphia, with nonfluent aphasia, typically reflects features of Broca’s aphasia, also referred to as nonfluent or motor aphasia. Letter and word output are lower than expected, with spelling errors due to letter omission. There may also be agrammatism marked by a paucity of prepositions and other grammatical elements, and calligraphy is poor. Dissociation may be present between written language and verbal language abilities, and written language may be inferior to verbal language.
    • Agraphia with Fluent Aphasia[10]
      • Agraphia, with fluent aphasia, typically reflects the impairments in Wernicke’s aphasia, also referred to as fluent or sensory aphasia. Patients characteristically produce a normal quantity of words with normal calligraphy, but the content is nonsensical. There may be neologisms (“jargonagraphia”), as well as the nonsensical use or placement of proper words. Grammatical elements may be overused in relation to nouns. Written language ability may be superior to verbal language—sometimes markedly so.[11]
    • Agraphia with Conduction Aphasia[12]
      • Agraphia with conduction aphasia has been rarely described. The hallmark of conduction aphasia is a characteristic impairment of repetition known as the “conduit d’approche”: the patient will incorrectly repeat a word, but will sequentially iterate through phonologically proximate variations until the correct pronunciation is reached. Written analogs of the “conduit d’approche” have been described in patients with conduction aphasia.
    • Alexia with Agraphia[13]
      • Alexia with agraphia simply refers to an impairment of both writing and reading ability, which can occur with or without aphasia. Patterns of written language impairment may follow those seen in the above categories.
  • Pure Linguistic Agraphia vs. Pure Apraxic Agraphia
    • An isolated impairment of writing that is not accompanied by any other language impairment or impairment in praxis can be considered “pure” agraphia. However, effort should be made to distinguish isolated agraphia due to a linguistic deficit from isolated agraphia due to writing apraxia.
    • Pure Linguistic Agraphia[14][15][16][17][18]
      • Pure linguistic agraphia is present when an isolated impairment in written language occurs as a result of a disruption to central linguistic processes involved in writing. Verbal language and reading abilities are intact. There may be semantic and/or orthographic errors in writing. Calligraphy quality is often normal. Case-based evidence suggests that pure linguistic agraphia may be further subdivided into phonological and lexical subtypes[11][19]. In phonological agraphia, there is an inability to spell pronounceable nonwords, and a retained ability to spell irregular words, which are exception words where spelling is dissociated from pronunciation--compare “steak” with “beak.” The reverse is found in lexical agraphia. Dyscravia is a more recently described disorder of phoneme-to-grapheme conversion in which written words are misspelled using proximate sounds, such as substituting a “t” for a “d”; dyscravia classifies as a subtype of phonological agraphia.[20]
    • Pure Apraxic Agraphia[17][21][22][23][24][25]
      • Pure apraxic agraphia is task-specific apraxia.[26] As with pure linguistic agraphia, in pure apraxic agraphia, there is an isolated impairment in written language in the presence of intact verbal language and reading ability. However, the writing impairment here stems from disruption to processes involved in the motor output of writing, downstream of linguistic processes. As such, impaired calligraphy is often considered a hallmark of apraxic agraphia. There should be no other manifestation of ideomotor or ideational apraxia for apraxic agraphia to be considered “pure.” In some cases of pure apraxic agraphia, findings may be as subtle as a selective impairment in font, such as cursive script (“allographic agraphia”), or case (such as an isolated inability to write in upper-case).[27][28]
    • Distinguishing between pure linguistic and pure apraxic agraphia
      • The distinction between pure linguistic apraxia and pure apraxic agraphia has been viewed as a significant diagnostic challenge. Certain techniques may help distinguish these two entities:[3]
      • Calligraphy (writing quality): Calligraphy is often impaired in pure apraxic agraphia. As such, several authors have suggested that the presence of intact calligraphy points to pure linguistic agraphia. However, it remains unclear if one can have an isolated impairment of calligraphy involving linguistic processes affected in central agraphia with nonfluent aphasia.
      • Spelling: Oral spelling, which is considered a non-motor modality of “writing,” maybe affected in linguistic agraphia, but intact in apraxic agraphia.
      • Copying: Writing that improves with copying written text may be useful in identifying pure linguistic agraphia, on the grounds that writing praxis is intact.
      • Non-motor writing: Besides oral spelling, other non-motor modalities to “write,” such as keyboard typing and mobile phone texting, may be preserved in pure apraxic agraphia and impaired in pure linguistic agraphia.
      • Pseudowords and irregular words: The writing of pseudowords and irregular words are used in the clinical neuropsychologic assessment of writing to localize disruptions in “phonological” and “lexical” processes, respectively.[11][29][30] Such techniques may help identify pure linguistic agraphias if writing impairments are limited to these specific linguistic features.
  • Peripheral (Nonlinguistic or Nonaphasic) Agraphia
    • Apraxic Agraphia[1][16]
      • In apraxic agraphia, there is an impairment in the motor planning of writing. Apraxic agraphia can occur with or without other forms of apraxia; when isolated, it can be designated as pure apraxic agraphia. Apraxic agraphia is most commonly a form of ideomotor apraxia, in which case the individual has a desire to write but is unable to do so. However, ideational agraphia--in which the knowledge of the concept of writing itself is lost--has also been described.[31]
      • Motor Agraphia
        • Motor agraphia is broad and occurs due to the disruption of the motor system downstream of praxis, anywhere from the motor cortex to the peripheral nerve and muscle. Paretic agraphia is a result of paresis regardless of localization. Micrographia is hypokinetic motor agraphia most commonly associated with Parkinsonism and attributed to bradykinesia; it is marked by a progressive decrement of handwriting size. Hyperkinetic agraphia can result from a number of movement disorders such as tremor or chorea. Writer’s cramp is a task-specific focal dystonia of forearm and hand muscles activated by writing. Writer’s cramp is considered simple when isolated to writing, and complex (or dystonic) when it carries over into other non-writing activities.[32]
      • Reiterative Agraphia
        • The reiterative agraphias include features such as perseveration, echographia (rewriting of phrases produced by the examiner), or paligraphia (rewriting of the same phrase produced by the patient).
    • Visuospatial Agraphia[33]
      • Visuospatial agraphia is writing impairment due to errors of orientation to the writing instrument and/or writing surface. One common cause of visuospatial agraphia is hemispatial neglect, where one is unaware of half of the page--most frequently this manifests with a blank left-hand side of a page. Other features suggesting visuospatial agraphia include errors of word spacing or word grouping, as well as specific letter-writing errors such as incorrectly repeating strokes, or even repeatedly writing the same letter multiple times. Letters or words may be superimposed. In these cases, writing errors are attributed to constructional apraxia. Note that the term “constructional apraxia” is a visuospatial disorder and does not refer to true apraxia (i.e., an error of a skilled motor task), and is not to be confused with apraxic agraphia.[34] Visuospatial agraphia can also be due to optic ataxia, in which there are errors of visual depth perception or oculomotor deficits.[35]
    • Functional (Psychogenic) Agraphia
      • Functional agraphia can also occur as a manifestation of conversion syndrome. As with other functional neurologic disorders, framing functional agraphia within the model of traditional neuroanatomic localization can be challenging.

Etiology

Central or linguistic agraphia can be caused by any lesion to the cortical language centers of the brain, or to any of their associated subcortical structures. This is classically studied in stroke, which remains the most common cause of language impairment in general.[36] Virtually any lesion affecting these areas, including trauma, tumors, and infections can result in central agraphia.

Neurodegenerative conditions such as Alzheimer disease or frontotemporal dementia can also lead to central agraphia, in which case the onset is gradual with progressive worsening. Primary progressive aphasia and its subtypes represent clinical neurodegenerative syndromes, which are characterized predominantly by slowly worsening language impairment; notably, Alzheimer disease and frontotemporal degeneration are implicated in the majority of these cases.[37][38] Agraphia is also considered the most common finding in delirium. However, delirium is nonspecific, and the etiologies of delirium are extremely varied.[1]

As with central agraphia, peripheral agraphia can be caused by a myriad of lesions anywhere from the cortex to the peripheral nerve and muscle. However, in peripheral agraphia, these lesions disrupt the motor planning or motor output of writing.

Epidemiology

Data on the incidence of acquired neurologic language impairment, including agraphia, is limited in general. Stroke is considered the most common cause of acquired language impairment.[1] One study in Switzerland found the annual incidence of language impairment due to first-ever ischemic stroke to be 47 in 100,000 total inhabitants; of these, 30% of stroke patients developed aphasia. This study included patients with agraphia, although the rate of agraphia is not specified.[39][36]

Pathophysiology

The pathophysiology of neurologic language impairment, including aphasia and agraphia, remains incompletely understood. In general, aphasia is better studied than agraphia and serves as the most common model for studying neurologic language processing. However, several reports have observed a dissociation between written language and verbal language ability, which suggest locations in the brain dedicated to writing.[7][10] With this said, several locations in the brain involved in the processing of language have been identified.

Classical localization methods based on vascular lesions originally identified two primary linguistic centers of the brain: these are Broca’s area in the dominant inferior frontal gyrus and Wernicke’s area in the dominant superior temporal gyrus. These areas are respectively supplied by the superior and inferior divisions of the middle cerebral artery. The left hemisphere is the dominant hemisphere in over 95% of right-handed and over 70% of left-handed individuals.[40] Lesions to Broca’s area typically lead to nonfluent language impairment; Broca’s area has been shown to be involved with linguistic functions, including fluency, phonological processing, grammar processing, and semantic retrieval.[41][42] 

Lesions to the inferior division of the middle cerebral artery are commonly attributed to “fluent” language impairment, characterized by nonsensical speech and impaired comprehension. It was initially believed and remains commonly taught that Wernicke’s area is involved in word recognition and word meaning. However, while more recent data reveals that Wernicke’s area is indeed involved with phonological language production, it may not be crucial for language recognition. Rather, the posterior cortical language area responsible for word recognition and word meaning--for which lesions produce a nonfluent or Wernicke’s aphasia--is spread more diffusely across the temporal and parietal lobes.[43]

There are areas of the brain that are thought to be dedicated to handwriting. The dominant angular gyrus is thought to be involved in the abstract conversion of verbal representation of language to visual representation. While hypothesized by some authors to be involved in reading ability, other authors consider this area to be dedicated to written language production and instead implicate the nearby lateral occipital gyri in disorders of reading.[13] Conversely, there is an area within the dominant middle frontal gyrus which has been referred to as the “graphemic/motor frontal area” (named in reference to a proposed “Exner’s area” of handwriting hypothesized by Siegmund Exner) which has been implicated as an interface between the abstract representation of words and the motor programming of writing.[44] Based on the above localization, it is plausible that lesions in the dominant angular gyrus may produce pure linguistic agraphia, and lesions to the middle frontal gyrus may produce pure apraxic agraphia.

Cases of lexical agraphia and phonological agraphia point to the existence of separate routes for lexical and phonological centers used for writing.[19] Of note, the graphemes of the English language--the letters of the Latin alphabet--are phonologic in nature, as they represent sounds. Research in agraphia in the Japanese language, which uses both morphologic and phonologic alphabets, gives support to the idea that there are separate morphologic and phonologic pathways for the production of reading and writing.[30][45][46][30]

While classic localization models remain clinically useful and aid in identifying cortical areas that are crucial in the various aspects of language, data increasingly support a network-based model of language processing. Functional imaging studies have revealed that language functions are more diffuse than previously thought.[47] Indeed, lesions to areas such as the cerebellum, thalamus, or even the nondominant hemisphere can mimic damage to Broca’s area or the posterior language area, which includes Wernicke’s area.[48][49] Similarly, clinical syndromes consistent with pure linguistic agraphia have been documented in the thalamus and internal capsule.[15][18]

In contrast to central agraphia, peripheral agraphia is much more varied in its pathophysiology and often localizes to one or more locations in the central and/or peripheral nervous system. The localization of apraxic agraphia is not standardized and has been most commonly documented with lesions in the frontal and parietal lobes, although lesions leading to apraxic agraphia have also been observed in thalamus and cerebellum.[16][23] The possible role of Exner’s area in pure apraxic agraphia is postulated above. Of note, the agraphia that is part of the tetrad of Gerstmann syndrome, which classically implicates the posterior lobule of the dominant parietal lobe, has recently been challenged to represent separate apraxic agraphia involving the neighboring superior parietal gyrus.[50]

Paretic motor agraphia can occur due to lesions anywhere in the corticospinal tract and associated muscles. Micrographia is associated with Parkinsonism, which itself is most commonly associated with lesions to the substantia nigra, but can also occur with lesions in the globus pallidus, striatum, or even the frontal lobe.[51] Agraphia, due to tremor or chorea, can occur due to lesions in structures modulating motor control, including the basal ganglia or cerebellum.

Reiterative agraphia may reflect phenomena of conditions such as catatonia or Tourette syndrome.[52] When this feature is a reflection of perseverative behavior, this is thought to broadly localize to the frontal or parietal lobe.[53][54] Lesions anywhere in the optic pathway or areas of cortical visual processing can lead to visuospatial agraphia. Neglect, which classically localizes to the nondominant parietal lobe, can also lead to visuospatial agraphia. Functional agraphia is complex in nature and often does not easily localize to any particular structure.

History and Physical

The evaluation of a patient’s writing ability is part of the complete Neurologic workup for language, which also includes fluency, comprehension, repetition, naming, and reading. The complete evaluation of both verbal and written language is essential to elucidating the cause of agraphia.

To assess writing in an English-speaking patient, the examiner should provide the patient with a writing instrument, a blank sheet of paper (or writing board), and a flat writing surface. Patients lying in bed should be positioned upright. The examiner should then ask the patient to write a complete and grammatically correct sentence. This can be as simple as asking the patient to “Please write me a sentence,” but it can be helpful to offer open-ended prompts such as “What did you do today?”, “Why are you here?” or “Tell me something about yourself.” The examiner should encourage the patient to make his or her handwriting clear and legible.

One should observe the patient for correct orientation to the page and writing instrument in space. The act of writing should be observed for the general ease and speed of the task. The letters should be relatively uniform in size, spacing, and stroke quality. The examiner should make a note of any errors of writing, including duplication of letter strokes, incorrect placement of spaces, or physical overlapping of words. Writing content should be analyzed for sentence length, word choice, accurate spelling, and correct use of grammatical elements and punctuation. Given the natural variation in individual handwriting, the examiner should compare pre-morbid writing samples if these are available, or ask the patient if their handwriting appears different than it was previously.

The presence or absence of other neurological exam findings may help include or exclude different etiologies of agraphia. Patients with central agraphia often have concomitant aphasia. In patients with apraxic agraphia, there may be a pertinent absence of paresis on manual muscle testing. Ideomotor apraxic agraphia may be accompanied by impaired use of other tools, and there can be deficits in mimicking tools such as a hammer or a toothbrush. Drawing an Archimedes spiral can help distinguish essential tremor from Parkinsonian tremor.[55] 

Micrographia can be accompanied by cogwheeling rigidity, decrements on fast finger tapping, or other features of Parkinsonism. An intact ability to copy a complex figure, such as the Rey-Osterrieth complex figure test, may help exclude constructional apraxia when assessing apraxic agraphia.[28]

Evaluation

Bedside examination of agraphia by a clinician provides the initial characterization of writing dysfunction. In equivocal cases, more extensive assessment can help further characterize an agraphia. Specialized tests such as the Western Aphasia Battery or Boston Diagnostic Aphasia Examination conducted by a speech and language pathologist can provide more granularity than a bedside clinical assessment, and can aid in tracking the severity of agraphia.[56] These tests may also be administered by a neuropsychologist or psychometrician as part of an extensive neuropsychological evaluation.

Once agraphia is identified, localization should be clinically correlated to determine the underlying cause of the agraphia and guide further diagnostic workup. In some cases, as in the writer’s cramp, history and examination are sufficient to establish a diagnosis. Brain imaging with computerized tomography (CT) or magnetic resonance imaging (MRI) is often useful to localize or identify lesions causing agraphia, especially if caused by stroke. Volumetric MRI or neuropsychological testing may be helpful in cases of suspected dementia. Dopamine transporter single-photon emission computed tomography with an injection of ioflupane I-123 may aid in distinguishing idiopathic Parkinsonism from drug-induced Parkinsonism or essential tremor.[57]

Treatment / Management

The correct classification of a patient’s agraphia is paramount to proper treatment, as treatments vary greatly depending on the localization and etiology of the agraphia. In general, therapy in the form of speech and language therapy (SLT) and occupational therapy is the cornerstone of treatment for both central and peripheral agraphia. Often, a multimodal approach including therapy, medication, and sometimes surgery is required to successfully treat agraphia: for example, a patient with micrographia due to Parkinson’s disease might require deep brain stimulation, antiparkinsonian medication, occupational therapy, and/or orthotic devices to optimally address his or her writing impairment.

In addition to addressing the symptoms of agraphia, it is essential to address the underlying etiology of agraphia to prevent potential progression of writing impairment. For instance, a patient with a tumor leading to central agraphia should be offered appropriate chemotherapy, radiation, and/or surgical treatments.

Of the various etiologies of central agraphia, the strongest evidence is in central agraphia due to stroke. SLT is shown to be beneficial for language impairment after stroke, with evidence that high dose SLT is favorable to low dose SLT for improving writing ability.[5] One small study of 8 patients with alexia and agraphia due to stroke found benefit in targeted task-specific training in reading and/or writing, suggesting that treatment protocols may benefit from widely targeting a variety of specific writing deficits.[58]

Limited evidence suggests that piracetam may be useful in agraphia in the acute setting after stroke.[59] Memantine has been shown to be effective in post-stroke aphasia but was not investigated for its efficacy on writing impairment.[60] Regarding neuromodulation, small trial data suggests a potential beneficial effect of transcranial magnetic stimulation on writing impairment after stroke, although larger studies are needed.[61]

The treatment of peripheral agraphia is broader than central agraphia and depends on the subtype of agraphia. Visuospatial agraphia due to hemispatial neglect, for instance, may benefit from prism lenses.[62] The writer’s cramp is often amenable to local botulinum toxin injection.[32] Orthotic devices, occupational therapy, and relaxation techniques may also help with symptoms of writer’s cramp.[63]

Differential Diagnosis

Agraphia is not a single entity but a neurologic symptom with a multitude of etiologies. The “differential” for agraphia includes illiteracy, in which the ability to write is not acquired. Agraphia should also be distinguished from abulia, which represents a generalized hypofunction and deficit of motivation.

Prognosis

The prognosis of agraphia is highly variable and depends on its etiology. Broadly speaking, language impairment after stroke follows a period of recovery that peaks around three months after a stroke, followed by an eventual plateau in language ability.[2][64] In contrast, central agraphia due to neurodegenerative diseases is expected to progressively worsen. Peripheral agraphias comprise a wide variety of etiologies that carry different prognoses.

Complications

Complications of agraphia include issues with community integration, where functional communication is vital to independent daily life. Language impairments can be frustrating for patients, and in stroke, they are also associated with depression.[65] As agraphia is not a specific disease, the complications of the underlying etiology should be considered.

Deterrence and Patient Education

Patients and families should be educated about the presence and features of acquired language impairment. In patients who are otherwise cognitively intact, isolated language impairment can often be mistaken for global cognitive impairment. Patients should be provided with communication strategies individualized to their impairment. Even in the presence of reading language deficits, it can be helpful to periodically provide written educational material to patients with language impairment.[66]

Pearls and Other Issues

As with the various classifications for the aphasias, there are many classification schemas to categorize the agraphias. One such clinical neurological schema is used in this article. However, neuropsychological or psycholinguistic schemas to classify agraphia are also commonly used.[1][2]

Similarly, definitions and terminology in the study of neurologic language impairment can frequently be ambiguous or contradictory, with certain trends appearing in the literature over time. This is likely due in part to an understanding of agraphia that has evolved alongside advances in technology.[67] Care is taken throughout this review to highlight relevant discrepancies and to minimize ambiguity.

In the assessment of agraphia, it is important to consider the level of education of a patient. Illiteracy, in which written ability is never acquired, must be distinguished from agraphia. Literacy rates may vary depending on the practice setting. The patient’s primary language should be considered, especially if it is different from the working language of the examiner. In-person or video-based professional language interpretation may be necessary for adequate assessment.

In our increasingly digitized world, the investigation of typing and texting--forms of non-motor writing--warrants consideration for inclusion into the standard clinical assessment of language.[9]

Enhancing Healthcare Team Outcomes

Language impairments can be frustrating for patients. When communicating with patients with language impairment in a healthcare setting, it is important to provide these individuals with ample time to express themselves and to make sure that communication that is related to them is clear and unambiguous. In a stroke, language impairments are associated with depression and poorer quality of life.[66] As such, the mental health of patients with language impairment should also be appropriately evaluated and addressed.

When working in a multi-disciplinary setting as in rehabilitation, good communication between team members is vital to success. Agraphia and its features can be subtle, and relaying specific clinical findings directly to therapists can help guide effective speech and occupational therapy.

Rehabilitation for agraphia, as with other forms of disability, should be tailored to the patient’s individual capacity and goals. The need for writing as a skill varies between patients. As communication with language is inherently a social activity, it is also valuable, whenever possible, to engage the family members of patients with agraphia to help determine the goals of therapy.[68]


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