Could pure agraphia be the only sign of stroke? Lessons from two case reports.

Agraphia is defined as the disruption of the previously intact writing skills due to an acquired brain damage. Stroke remains the most common cause of language impairment; however, writing disorders, including agraphia, are underestimated in patients with stroke. In this regard, we report two patients presenting with pure agraphia as an early symptom of stroke. Both patients complained of at least two difficulties in visualizing letter formation beforehand, the frequent need for verbal cues, misuse of lines and margins, poorly legible signature, and writing and thinking at the same time (e.g., creative thinking and taking notes). They underwent brain magnetic resonance imaging which revealed a small lacunar infarction of the left insula and external capsule (patient 1) and a small hemorrhagic lesion in the posterior limb of the left internal capsule (patient 2). To our knowledge, this is the first report on pure agraphia as the presenting symptom of stroke. We suggest that all patients with acute agraphia, even when presenting as an isolated symptom, should be evaluated for stroke, in order to better facilitate its diagnosis and treatment.

Introduction

Agraphia is defined as the disruption of the previously intact writing skills due to an acquired brain damage, including stroke.[1] Specifically, agraphia consists of the inability to communicate through writing owing to the involvement of at least one among language processing, spelling, visual perception, visuo-spatial orientation for graphic symbols, motor planning, and writing motor control. Agraphia can be broadly divided into central and peripheral categories. Central agraphias typically involve language areas of the brain (although many other areas may be involved as per the network-based model), causing difficulty spelling or with spontaneous communication. Peripheral agraphias usually target motor and visuospatial skills in addition to language and tend to involve motoric areas of the brain, causing difficulty in the movements associated with writing.[2]

Central agraphia may occur in association with other language disorders, including aphasias, alexia, agnosia, and apraxia, otherwise, it is called pure agraphia.[23] This can be labeled as pure “apraxic” or “linguistic (aphasic)” agraphia; the former depends on the disruption to processes involved in the motor output of writing and shows impairment in calligraphy and preservation of oral spelling, copying, nonmotor writing, and writing of irregular words, whilst the latter depends on the disruption to central linguistic processes involved in writing.[12]

Stroke is the most common cause of language impairment, aphasia being the main symptom that can be associated with other speech and writing disorders.[4] As agraphia rarely manifests as the only sign of brain injury and it is not usually investigated during the routine neurological examination, the symptom might be underestimated.[12]

In this regard, we report on two patients presenting with pure “apraxic” agraphia as an early symptom of stroke, ascribed to specific stroke neuroradiological patterns.

Case Description

Patient 1 was a 55-year-old man, right-handed. Family history was positive for cardiovascular diseases. He was a current strong smoker (about 20 cigarettes per day since adolescence). About 3 days before the medical consult, he started to complain of poorly legible signature, difficulty in visualizing letter formation beforehand and in writing and thinking at the same time (e.g., creative thinking and taking notes), as well as misuse of lines and margins. Such symptoms progressively worsened over 2 days, together with a feeling of heavy head and dizziness. At the emergency room consultation, he did not disclose muscle weakness or sensory deficits. When he was in the neurological ward, language skills, with regard to spontaneous handwriting, writing to dictation, and copying were investigated. Particularly, his writing was characterized by poorly formed graphemes with a laborious and slow formation of distorted, incomplete and/or inaccurate letters and words, and inability to write on a line and to copy [Figure 1]. The ability to spell aloud was preserved. He scored 206/232 at the quick aphasia battery (QAB),[5] owing to a moderate-to-severe impairment in the connectedness of writing (QAB subitems: word comprehension 30; sentence comprehension 30; word-finding 24; grammar construction 17; speech motor programming 29; repetition 28; reading 30). At the Montreal Cognitive Assessment (MOCA) he scored 30/30, and the Addenbrooke's Cognitive Examination (ACE-R) was normal, but the language writing score was 0/2. Moreover, limb-kinetic apraxia was ruled out, as he was able, e.g., to tie shoelace and button a shirt. Cardiovascular screening (including electrocardiogram, echocardiogram, and carotid doppler ultrasound) was within the normal range. He underwent a brain MRI showing a lacunar infarct within the left insular subcortical white matter [Figure 2]. He was thus prescribed acetylsalicylic acid (100 mg/day) with regression of symptomatology within about 2 weeks.

Figure 1

Shows the spontaneous writing, writing to dictation, and copying with some paragraphic elements of patient 1

Figure 2

Axial DWI-weighted (left panel) and axial T2-weighted images (right panel) of patient 1, performed 8 days after agraphia onset, showing a small area with restricted diffusion at the DWI-weighted images and hyperintense signal and the T2-weighted images within the left insular subcortical white matter, consistent with a lacunar infarct

Patient 2 was a 61-year-old man, right-handed. Family history was positive for cardiovascular and cerebrovascular diseases. He was a heavy smoker: about 30 cigarettes per day (from adolescence until 17 years ago). About 2 days before medical consultation, he started to complain of difficulty in writing with misuse of lines and margins, and frequent need of verbal cues on how to write a word. The writing was also poorly legible owing to inconsistent form and size of letters, or unfinished letters. At the emergency room consultation, he also complained of hand clumsiness and numbness without limb-kinetic apraxia, as well as mild dysarthria. The MOCA (30/30) and ACE-R test did not reveal other neuropsychological deficits. The patient was tested for spontaneous handwriting (he was invited to write about a picture), writing to dictation, and copying. Particularly, his writing was characterized by distorted graphemes, missing letters, truncated words, and the inability to write on a line and to copy. The ability to spell out loud was preserved. He scored 202/232 at the QAB (QAB subitems: word comprehension 30; sentence comprehension 30; word-finding 18; grammar construction 11; speech motor programming 30; repetition 29; reading 30). He, thus, underwent a brain MRI showing a hemorrhagic lesion within the posterior limb of the left internal capsule [Figure 3]. The cardiovascular screening was within the normal range, but high blood pressure values and mild-moderate carotid intimal thickness. He was thus prescribed enalapril (20 mg per day), furosemide (20 mg per day), and carvedilol (6.5 mg per day). Symptoms resolved within about 10 days.

Figure 3

Axial FLAIR (left panel) and SWI images (right panel) of patient 2, performed 5 days after agraphia onset, showing a small area with the hyperintense signal at FLAIR images and hypointense signal at SWI images within the posterior limb of the left internal capsule, consistent with a hemorrhagic focus

Discussion

Both patients complained of pure “apraxic” agraphia due to a cerebrovascular accident. Clinical diagnosis of a stroke was considered because of the acute onset of a communication disorder, i.e., agraphia, as a possible focal warning sign of the disease. The diagnosis was then corroborated by the accurate medical history and the specific neurological examination, including the assessment of both oral and writing language and the use of specific neuropsychological tests, and it was eventually confirmed by neuroimaging data. Actually, the patients showed an isolated impairment in written language with impaired calligraphy and copying in the presence of preserved spelling, nonmotor writing (i.e., keyboard typing and mobile phone texting), intact verbal language, and reading ability.[12] Noteworthy, this is the first report on pure agraphia as an early warning symptom of stroke. Despite agraphia is common in persons with stroke,[12] pure agraphia has been rarely described in the literature.[6] In the last 2 decades, there are only reports on progressively developing agraphia some months before stroke onset, agraphia associated with pure motor deficits, or particular cortical stroke localizations in relation to agraphia.[1267] The lack of reports on early isolated agraphia in stroke may be related either to a nonspecific assessment of writing during anamnesis and neurologic investigation or to other symptoms (with regard to aphasia and apraxia) masking agraphia, which may occur when, e.g., the patient does not enter medical consultation at the agraphia onset but only later.

Another main novelty of our case reports is that specific brain damage locations outside the language areas (due to either ischemic or hemorrhagic stroke) can cause pure agraphia. A damage to the angular gyrus of the dominant side may produce pure linguistic agraphia, whereas lesions to the middle frontal gyrus may produce pure apraxic agraphia.[3] Nonetheless, brain imaging in our patients revealed damage to the insula and the internal and external capsules of the dominant hemisphere. These lesion patterns suggest that both patients had involvement of the motor output of writing downstream of linguistic processes. Furthermore, this lesion pattern may suggest the specific, distinct pathways for handwriting could exist, which probably form a greater network model of language processing.[38910] Actually, other brain languages, including nonperisylvian regions, supramarginal gyrus, insula, posterior temporal area, and nondominant parietal lobe areas could indeed contribute to pure agraphia.[38910] Thus, more studies using both structural [e.g., diffusion tensor imaging (DTI)] and functional [functional MRI (fMRI), electroencephalography (EEG), transcranial magnetic stimulation (TMS)] approaches are needed to better understand the neural networks subtending writing.

In conclusion, we suggest that all patients with acute agraphia, even when presenting as an isolated symptom, should be evaluated for stroke, in order to better facilitate its diagnosis and treatment. Actually, agraphia as the only presentation of stroke might result in insufficient medical care as the disorder is not usually investigated during a neurological examination. Although every minor or major symptom with an acute onset should arise the suspicion of a stroke, at the emergency department some isolated neurological signs, like agraphia, are not easily assessable. Further neuroimaging data and an extensive battery of neuropsychological and neurobehavioral tasks would be necessary when dealing with pure agraphia to better characterize and manage this important function.

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Conflicts of interest

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