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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 (linguistic or aphasic agraphia) and peripheral agraphia (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 letters of the Latin alphabet. To write properly, one must first know the letters themselves and then 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 know the set of coordinated movements to draw out letters (praxis) correctly, 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 motor agraphia due to a motor cortex lesion leading to the paresis of the writing limb.
Clinical neurologic and neuropsychological classification schemas exist to categorize the agraphia, and a clinical neurologic classification is used in this review. Pure agraphia is a term 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, others try to distinguish between pure linguistic (or aphasic) agraphia and pure apraxic agraphia.[3] This review agrees with making this distinction on 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 both written and spoken language impairments.[2][4][5]
This topic uses aphasia to refer to an isolated spoken language impairment. The peripheral agraphias can be viewed as analogous to dysarthria of written language in the sense that dysarthria denotes an impairment in the motor output of verbal language. Furthermore, in central agraphia, there can 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 written and spoken language issues.
Agraphia is distinguished from illiteracy, in which 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. 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, which is 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. Cases of isolated dystypia or dystextia suggest these may represent distinct impairments.[9]
Central (Linguistic) Agraphia
Agraphia with nonfluent aphasia
Along with nonfluent aphasia, agraphia 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. Agrammatism may also be marked by a paucity of prepositions and other grammatical elements, and calligraphy is poor. Dissociation between written language and verbal language abilities may be present, and written language may be inferior to verbal language.
Agraphia with fluent aphasia
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) and 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.[10][11]
Agraphia with conduction aphasia
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 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.[12]
Alexia with agraphia
Alexia with agraphia 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.[13]
Pure linguistic agraphia versus 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
Pure linguistic agraphia is present when an isolated impairment in written language occurs due to a disruption to central linguistic processes involved in writing. Verbal language and reading abilities are intact. There may be semantic or orthographic errors in writing. Calligraphy quality is often normal. Case-based evidence suggests that pure linguistic agraphia may be subdivided into phonological and lexical subtypes. In phonological agraphia, there is an inability to spell pronounceable non-words and a retained ability to spell irregular words, except for 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.[11][14][15][16][17][18][19][18][20]
Pure Apraxic Agraphia
Pure apraxic agraphia is task-specific apraxia. 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).[17][21][22][23][24][25][26][27]
Distinguishing Between Pure Linguistic and Pure Apraxic Agraphia
The distinction between pure linguistic apraxia and pure apraxic agraphia has been considered a significant diagnostic challenge. Certain techniques may help distinguish these 2 entities:
- Calligraphy (writing quality): Calligraphy is often impaired in pure apraxic agraphia. As such, several authors have suggested that 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, considered a non-motor writing modality, may be 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 because the writing praxis is intact.
- Non-motor writing: Besides oral spelling, other non-motor writing modalities, 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 is used in the clinical neuropsychologic writing assessment to localize phonological and lexical process disruptions, respectively. Such techniques may help identify pure linguistic agraphia if writing impairments are limited to these linguistic features.[3][11][28][29]
Peripheral (Nonlinguistic or Nonaphasic) Agraphia
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 the individual desires to write but cannot do so. However, ideational agraphia--in which the knowledge of the concept of writing itself is lost--has also been described.[30]
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 in handwriting size. Hyperkinetic agraphia can result from several movement disorders, such as tremors or chorea. The writer’s cramp is task-specific focal dystonia of the forearm and hand muscles activated by writing. A writer’s cramp is considered simple when isolated to writing and complex (or dystonic) when it carries over into other non-writing activities.[31]
Reiterative agraphia
The reiterative agraphia includes 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
Visuospatial agraphia is writing impairment due to errors of orientation to the writing instrument or 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 and 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 constructional apraxia is a visuospatial disorder that does not refer to true apraxia (ie, an error of a skilled motor task) and is not to be confused with apraxic agraphia.[32] Visuospatial agraphia can also be due to optic ataxia, in which visual depth perception errors or oculomotor deficits occur.[33][34]
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
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Etiology
Any lesion can cause central or linguistic agraphia to the cortical language centers of the brain or any of their associated subcortical structures. This is classically studied in stroke, which remains the most common cause of language impairment in general.[35] Virtually any lesion affecting these areas, including trauma, tumors, and infections, can result in central agraphia. Agraphia can present as a symptom of chemotoxicity, transient headache, and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) or COVID-19 infection.[36][37][38]
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.[39][40] 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 many 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 generally limited. 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 a 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.[35][41]
Pathophysiology
The pathophysiology of neurologic language impairment, including aphasia and agraphia, remains incompletely understood. Generally, aphasia is better studied than agraphia and is the most common model for neurologic language processing. However, several reports have observed a dissociation between written language and verbal language ability, which suggests locations in the brain dedicated to writing.[7][10] With this said, several locations in the brain involved in language processing have been identified.
Classical localization methods based on vascular lesions originally identified 2 primary linguistic centers of the brain: Broca's area in the dominant inferior frontal gyrus and Wernicke’s area in the dominant superior temporal gyrus. The superior and inferior divisions of the middle cerebral artery supply these areas. The left hemisphere is the dominant hemisphere in over 95% of right-handed and over 70% of left-handed individuals.[42] Lesions to Broca's area typically lead to nonfluent language impairment; Broca’s area involves linguistic functions, including fluency, phonological processing, grammar processing, and semantic retrieval.[43][44]
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 involves word recognition and 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 meaning—for which lesions produce nonfluent or Wernicke's aphasia—is spread more diffusely across the temporal and parietal lobes.[45]
Some areas of the brain are thought to be dedicated to handwriting. The dominant angular gyrus is believed 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 reading disorders.[13] Conversely, there is an area within the dominant middle frontal gyrus that has been referred to as the graphemic or motor frontal area (named after a proposed Exner 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.[46] 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 and phonological agraphia point to 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, supports the idea that there are separate morphologic and phonologic pathways for the production of reading and writing.[29][47][48]
While classic localization models remain clinically useful and aid in identifying cortical areas crucial in various aspects of language, data increasingly support a network-based language processing model. Functional imaging studies have revealed that language functions are more diffuse than previously thought.[49] Indeed, lesions to areas such as the cerebellum, thalamus, or even the nondominant hemisphere can mimic damage to Broca's or the posterior language area, including Wernicke's area.[50][51] 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 or peripheral nervous system. The localization of apraxic agraphia is not standardized and has been most commonly documented with frontal and parietal lobes lesions. However, lesions leading to apraxic agraphia have also been observed in the 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.[52]
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. Still, it can also occur with lesions in the globus pallidus, striatum, or even the frontal lobe.[53] Due to tremors or chorea, agraphia 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.[54] When this feature reflects perseverative behavior, it is thought to be localized broadly to the frontal or parietal lobe.[55][56] 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 and often does not easily localize to any particular structure.
History and Physical
Evaluating a patient’s writing ability is part of the complete neurologic workup for language, including fluency, comprehension, repetition, naming, and reading. The complete evaluation of verbal and written language is essential to elucidate the cause of agraphia.
To assess writing in an English-speaking patient, the examiner should provide a writing instrument, a blank sheet of paper (or a 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 their handwriting clear and legible.
Clinicians should observe the patient to ensure correct orientation to the page and to write the 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 note any errors in 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. There may be a pertinent absence of paresis on manual muscle testing in patients with apraxic agraphia. 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 tremors from Parkinsonian tremors.[57]
Micrographia can be accompanied by cogwheeling rigidity, decrements in 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.[27]
Evaluation
A clinician's bedside examination of agraphia provides the initial characterization of writing dysfunction. In equivocal cases, a more extensive assessment can help further characterize 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.[58] A neuropsychologist or psychometrician may also administer these tests 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.[59]
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, speech and language therapy (SLT) and occupational therapy are the cornerstones of treatment for both central and peripheral agraphia. Often, a multimodal approach including therapy, medication, and sometimes surgery is required to treat agraphia successfully: for example, a patient with micrographia due to Parkinson disease might require deep brain stimulation, antiparkinsonian medication, occupational therapy, or orthotic devices to address their writing impairment optimally.
In addition to addressing the symptoms of agraphia, it is essential to address the underlying etiology of agraphia to prevent the potential progression of writing impairment. For instance, a patient with a tumor leading to central agraphia should be offered appropriate chemotherapy, radiation, 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 or writing, suggesting that treatment protocols may benefit from widely targeting a variety of specific writing deficits.[60](A1)
Limited evidence suggests that piracetam may be useful in agraphia in the acute setting after a stroke.[61] Memantine is effective in post-stroke aphasia but was not investigated for its efficacy on writing impairment.[62] Regarding neuromodulation, small trial data suggests a potential beneficial effect of transcranial magnetic stimulation on writing impairment after stroke, although larger studies are needed.[63][64](A1)
- The treatment of peripheral agraphia is broader than central agraphia and depends on the subtype of agraphia. For instance, visuospatial agraphia due to hemispatial neglect may benefit from prism lenses.[65] The writer’s cramp is often amenable to local botulinum toxin injection.[31] Orthotic devices, occupational therapy, and relaxation techniques may also help with a writer’s cramp symptoms.[66] (A1)
Differential Diagnosis
Agraphia is not a single entity but a neurologic symptom with many etiologies. The differential for agraphia includes illiteracy, in which the ability to write is not acquired. Agraphia should also be distinguished from abulia, representing a generalized hypofunction and motivational deficit.
Prognosis
The prognosis of agraphia is highly variable and depends on its etiology. Language impairment after a stroke follows a period of recovery that peaks around three months after a stroke, followed by an eventual plateau in language ability.[2][67] In contrast, due to neurodegenerative diseases, central agraphia is expected to worsen progressively. 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.[68] 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 otherwise cognitively intact patients, 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 provide written educational material to patients with language impairment periodically.[69]
Pearls and Other Issues
As with the various classifications for aphasias, there are many classification schemas to categorize 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 partly to an understanding of agraphia that has evolved alongside technological advances.[70] Care is taken throughout this review to highlight discrepancies and minimize ambiguity.
In assessing agraphia, it is essential to consider a patient's education level. 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 differs from the examiner's working language. 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 nonmotor writing—warrants consideration for inclusion in the standard clinical language assessment.[9]
Enhancing Healthcare Team Outcomes
Language impairments can be frustrating for patients. When communicating with patients with language impairments in a healthcare setting, it is important to provide ample time for them to express themselves and ensure that communication is clear and unambiguous. In stroke, language impairments are associated with depression and poorer quality of life.[69] As such, the mental health of language-impaired patients should also be appropriately evaluated and addressed.
Good communication between interprofessional team members is vital to success in an interprofessional setting, as in rehabilitation. 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 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 therapy goals.[71]
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