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.

Asymmetric Bálint's syndrome with multimodal agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading due to subcortical hemorrhage in the left parieto-occipito-temporal area.

We report a patient with asymmetric Bálint's syndrome (predominantly right-sided oculomotor apraxia and simultanagnosia and optic ataxia for the right hemispace), and multimodal agnosia (apperceptive visual agnosia and bilateral associative tactile agnosia) with accompanying right hemianopia, bilateral agraphesthesia, hemispatial neglect, global alexia with unavailable kinesthetic reading, and lexical agraphia for kanji (Japanese morphograms), after hemorrhage in the left parieto-occipito-temporal area. The coexistence of tactile agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading suggests that tactile-kinesthetic information can be interrupted because of damage to the fiber connection from the parietal lobe to the occipito-temporal area, leading to these tactually related cognitive impairments.

Alexia and agraphia in Spanish.

BACKGROUND: Every language has certain specific idiosyncrasies in its writing system. Cross-linguistic analyses of alexias and agraphias are fundamental to understand commonalities and differences in the brain organization of written language. Few reports of alexias and agraphias in the Spanish language are currently available. AIMS: To analyse the clinical manifestations of alexias and agraphias in Spanish, and the effect of demographic variables. METHODS & PROCEDURES: Spanish versions of the Western Aphasia Battery (WAB) and Boston Diagnostic Aphasia Examination (BDAE) were used for language assessment. Lesion localization was obtained by using computed axial tomography and magnetic resonance imaging. The final sample included 200 patients: 195 (97.5%) right-handed and five (2.5%) left-handed; 119 men and 81 women with a mean age of 57.37 years (SD = 15.56), education of 13.52 years (SD = 4.08), and mean time post-onset of 6.58 months (SD = 12.94). Using the WAB, four quotients were calculated: aphasia quotient (AQ), reading-writing quotient (RWQ), language quotient (LQ) and cortical quotient (CQ). OUTCOMES & RESULTS: The types of aphasia were: global = 11 patients (5.5%), Broca = 31 (15.5%), Wernicke = 30 (15.0%), conduction = 22 (11.0%), transcortical sensory = 17 (8.5%), transcortical motor = 3 (1.5%), amnesic or anomic = 54 (27.0%) and mixed non-fluent = 32 (16.0%). The degree of oral and written language impairment differed across the various aphasia types. Most severe reading and writing difficulties were found in global, mixed non-fluent and transcortical motor aphasia; fewer difficulties were observed in amnesic, Broca and conduction aphasia. The severity of the written language impairments paralleled the severity of the oral language disturbances. Age negatively, while schooling positively, correlated with the scores in reading and writing tests. No effect of sex and time since onset was found. CONCLUSIONS & IMPLICATIONS: In Spanish-speaking aphasia patients, difficulties in reading and writing are similar to oral language difficulties. This similarity of performance is mostly based on severity rather than the participants' patterns of errors. What this paper adds What is already known on the subject There is limited information about alexia and agraphia in Spanish. What this paper adds to existing knowledge An extensive study with a large sample of patients. What are the potential or actual clinical implications of this work? The study contributes to the clinical management of patients with reading and writing disturbances.

Selective impairment of On-reading (Chinese-style pronunciation) in alexia with agraphia for kanji due to subcortical hemorrhage in the left posterior middle temporal gyrus.

We report a patient with alexia with agraphia for kanji after hemorrhage in the left posterior middle temporal gyrus. The results of single-character kanji reading and two-character on- (Chinese-style pronunciation), kun- (native Japanese pronunciation), and Jukujikun (irregular kun-) reading word tests revealed that the patient could not read kanji characters with on-reading but read the characters with kun-reading. We consider that this on-reading alexia was caused by disconnection between the posterior inferior temporal cortex (orthographic lexicon) and the posterior superior temporal gyrus (phonological lexicon), and preserved kun- and Jukujikun-reading was realized by bypassing the orthography-to-phonology route by the semantic route.

Evaluating Spelling in Glioma Patients Undergoing Awake Surgery: a Systematic Review.

A main goal of awake surgery is to preserve language in order to facilitate return to work and maintain quality of life. Although spelling has become crucial in daily life, it has received little attention in awake surgery practice. We review assessments of spelling carried out in awake surgery studies, to inspect how current neurofunctional theories of spelling may guide pre-, intra- and post-operative neurosurgical practice. A systematic database search in Embase, Medline, PubMed and Web of Science identified studies reporting on spelling assessment in glioma patients undergoing awake surgery. Twenty-three studies were included, of which only 9 report details on spelling assessments. We evaluate the incidence of dysgraphia in glioma patients, the types of spelling errors as a function of tumor location, and the specificity of spelling sites with respect to other language functions. Post-operative dysgraphia arose in 26.9% of the patients with preserved pre-operative handwriting, and persisted in 45.0% of them at follow-up. Intra-operative stimulation interfered only with handwriting in 37.7% of the patients. A network of frontal, parietal and temporal regions was found to underlie central and peripheral spelling processes. Evidence on spelling performance in patients undergoing awake surgery for gliomas is surprisingly scarce. With the limitations inherent in the small number of observations, results converge with the neurofunctional knowledge accruing from studies of stroke cases. Such knowledge should be exploited in more thorough investigations of spelling skills in glioma patients. Implications for clinical and neuroscientific practice are discussed, as well as possible strategies to overcome current limitations.

A deficit in post-graphemic writing processes: Evidence for a graphomotor buffer.

Post-graphemic writing processes transform abstract letter representations into representations of writing movements. We describe an individual with an acquired post-graphemic writing deficit. NGN is normal in spelling words aloud, but impaired in writing words to dictation, with most errors involving letter substitutions (e.g., RUMOR written as BUMOR). NGN's deficit affects graphic motor plans, which specify the writing strokes for producing letters. Analyses of writing speed, fluency, and stroke patterns suggest that NGN's errors result from incomplete motor-plan activation. NGN's error rate is high for the first letter in a word, and declines across subsequent positions. On the basis of this serial position effect and other results, we propose that post-graphemic writing mechanisms include a graphomotor buffer, a writing-specific working memory that holds activated graphic motor plans bound to specific serial positions. We suggest that NGN's graphomotor buffer is damaged such that early serial positions are affected most severely. Finally, we present results speaking to the roles and capabilities of the graphomotor buffer, and the structure of graphic motor plans.

A phonetic radical account of the phonology-to-Orthography consistency effect on writing Chinese characters: Evidence from a Chinese Dysgraphic patient.

This study investigated the sublexical route in writing Chinese characters. Using a writing-to-dictation task, we compared neurotypical participants' performance on writing a set of 40 characters with homophones sharing different phonetic radicals and another set of 40 characters with homophones sharing the same phonetic radicals. The first set of stimuli was regarded as both syllable-to-character and syllable-to-radical inconsistent, while the second set of stimuli was considered syllable-to-radical consistent but syllable-to-character inconsistent. The results of the error analysis showed that the control participants demonstrated a greater tendency to make errors with preserved phonetic radicals in the second set of stimuli. Furthermore, we conducted the same task with a Chinese brain-injured patient, WCY, who had mild dyslexia and severe dysgraphia associated with mild impairment to the lexical semantic route as shown by the patient's character writing. The results showed that WCY demonstrated similar error patterns as those of the control participants and a shorter writing time in the second set of stimuli. Altogether, the observations were taken as evidence that supported our claim that a syllable-to-phonetic radical route governs the sublexical route in Chinese character writing.

Developmental surface dysgraphia without surface dyslexia.

The case is reported of an individual (N.K.) with a developmental spelling impairment (dysgraphia) who has no apparent problems in reading. His performance therefore provides further evidence of a classical dissociation between impaired spelling and preserved reading in individuals with developmental literacy problems. The dissociation is observed when N.K. is asked to read and spell in either his first (Greek) or his second language (English). An investigation of his spelling performance revealed that his impairment was more selective than that of P.J.T. Although his spelling of regular words and nonwords was normal, N.K. had a problem in spelling words with atypical sound-letter associations despite having no problems in reading aloud or understanding the meaning of words of this kind. It is argued that N.K.'s pattern of performance can be best explained in terms of normal development of an orthographic system that allows access to the meaning and pronunciation of written words during reading. In terms of a dual-route model of spelling, his poor spelling appears to be the result of a developmental impairment that impedes access to the orthographic system from phonology and semantics. In terms of the triangle model, his poor spelling appears to be the result of a developmental impairment that affects activation of orthography from semantics.

Apraxic agraphia following thalamic damage: Three new cases.

Apraxic agraphia (AA) is a so-called peripheral writing disorder following disruption of the skilled movement plans of writing while the central processes that subserve spelling are intact. It has been observed in a variety of etiologically heterogeneous neurological disorders typically associated with lesions located in the language dominant parietal and frontal region. The condition is characterized by a hesitant, incomplete, imprecise or even illegible graphomotor output. Letter formation cannot be attributed to sensorimotor, extrapyramidal or cerebellar dysfunction affecting the writing limb. Detailed clinical, neurocognitive, neurolinguistic and (functional) neuroimaging characteristics of three unique cases are reported that developed AA following a thalamic stroke. In marked contrast to impaired handwriting, non-handwriting skills, such as oral spelling, were hardly impaired. Quantified Tc-99m ECD SPECT consistently showed a decreased perfusion in the anatomoclinically suspected prefrontal regions. The findings suggest crucial involvement of the anterior (and medial) portion of the left thalamus within the neural network subserving the graphomotor system. Functional neuroimaging findings seem to indicate that AA after focal thalamic damage represents a diaschisis phenomenon.

Double-letter processing in surface dyslexia and dysgraphia following a left temporal lesion: A multimodal neuroimaging study.

Neuropsychological data about acquired impairments in reading and writing provide a strong basis for the theoretical framework of the dual-route models. The present study explored the functional neuroanatomy of the reading and spelling processing system. We describe the reading and writing performance of patient CF, an Italian native speaker who developed an extremely selective reading and spelling deficit (his spontaneous speech, oral comprehension, repetition and oral picture naming were almost unimpaired) in processing double letters associated with surface dyslexia and dysgraphia, following a tumor in the left temporal lobe. In particular, the majority of CF's errors in spelling were phonologically plausible substitutions, errors concerning letter numerosity of consonants, and syllabic phoneme-to-grapheme conversion (PGC) errors. A similar pattern of impairment also emerged in his reading behavior, with a majority of lexical stress errors (the only possible type of surface reading errors in the Italian language, due the extreme regularity of print-to-sound correspondence). CF's neuropsychological profile was combined with structural neuroimaging data, fiber tracking, and functional maps and compared to that of healthy control participants. We related CF's deficit to a dissociation between impaired ventral/lexical route (as evidenced by a fractional anisotropy - FA decrease along the inferior fronto-occipital fasciculus - IFOF) and relatively preserved dorsal/phonological route (as evidenced by a rather full integrity of the superior longitudinal fasciculus - SLF). In terms of functional processing, the lexical-semantic ventral route network was more activated in controls than in CF, while the network supporting the dorsal route was shared by CF and the control participants. Our results are discussed within the theoretical framework of dual-route models of reading and spelling, emphasize the importance of the IFOF both in lexical reading and spelling, and offer a better comprehension of the neurological and functional substrates involved in written language and, in particular, in surface dyslexia and dysgraphia and in doubling/de-doubling consonant sounds and letters.

What letters can "learn" from Arabic digits--fMRI-controlled single case therapy study of peripheral agraphia.

Research on (hand-)writing has revealed that Exner's area subserves transferring linguistic impulses into writing programmes. We report on a patient with a lesion affecting Broca's and Exner's area suffering from severe peripheral agraphia for letters but not for Arabic digits. Analogous to semantic (magnitude) information in numbers, we developed a specifically tailored writing training: additional mental imagery based semantic information was attached to letters. The training resulted in significant improvements. Imaging data revealed stronger fronto-parietal network activity including perilesional activation around Exner's area and precuneus for writing letters to dictation than for writing letters corresponding to their mental image expressions. Follow-up testing showed not only stable training effects but also an activation shift into the left angular gyrus. Results document neuronal correlates of a successful intervention by attaching additional meanings to letters in order to retrieve their grapho-motor patterns. These findings contribute to understanding the impact of Exner's area.

Contrasting brain patterns of writing-related DTI parameters, fMRI connectivity, and DTI-fMRI connectivity correlations in children with and without dysgraphia or dyslexia.

Based on comprehensive testing and educational history, children in grades 4-9 (on average 12 years) were diagnosed with dysgraphia (persisting handwriting impairment) or dyslexia (persisting word spelling/reading impairment) or as typical writers and readers (controls). The dysgraphia group (n = 14) and dyslexia group (n = 17) were each compared to the control group (n = 9) and to each other in separate analyses. Four brain region seed points (left occipital temporal gyrus, supramarginal gyrus, precuneus, and inferior frontal gyrus) were used in these analyses which were shown in a metaanalysis to be related to written word production on four indicators of white matter integrity and fMRI functional connectivity for four tasks (self-guided mind wandering during resting state, writing letter that follows a visually displayed letter in alphabet, writing missing letter to create a correctly spelled real word, and planning for composing after scanning on topic specified by researcher). For those DTI indicators on which the dysgraphic group or dyslexic group differed from the control group (fractional anisotropy, relative anisotropy, axial diffusivity but not radial diffusivity), correlations were computed between the DTI parameter and fMRI functional connectivity for the two writing tasks (alphabet and spelling) by seed points. Analyses, controlled for multiple comparisons, showed that (a) the control group exhibited more white matter integrity than either the dysgraphic or dyslexic group; (b) the dysgraphic and dyslexic groups showed more functional connectivity than the control group but differed in patterns of functional connectivity for task and seed point; and (c) the dysgraphic and dyslexic groups showed different patterns of significant DTI-fMRI connectivity correlations for specific seed points and written language tasks. Thus, dysgraphia and dyslexia differ in white matter integrity, fMRI functional connectivity, and white matter-gray matter correlations. Of clinical relevance, brain differences were observed in dysgraphia and dyslexia on written language tasks yoked to their defining behavioral impairments in handwriting and/or in word spelling and on the cognitive mind wandering rest condition and composition planning.

Language-specific dysgraphia in Korean patients with right brain stroke: influence of unilateral spatial neglect.

The purpose of the present study was to investigate the relationship between Korean language-specific dysgraphia and unilateral spatial neglect in 31 right brain stroke patients. All patients were tested for writing errors in spontaneous writing, dictation, and copying tests. The dysgraphia was classified into visuospatial omission, visuospatial destruction, syllabic tilting, stroke omission, stroke addition, and stroke tilting. Twenty-three (77.4%) of the 31 patients made dysgraphia and 18 (58.1%) demonstrated unilateral spatial neglect. The visuospatial omission was the most common dysgraphia followed by stroke addition and omission errors. The highest number of errors was made in the copying and the least was in the spontaneous writing test. Patients with unilateral spatial neglect made a significantly higher number of dysgraphia in the copying test than those without. We identified specific dysgraphia features such as a right side space omission and a vertical stroke addition in Korean right brain stroke patients. In conclusion, unilateral spatial neglect influences copy writing system of Korean language in patients with right brain stroke.

Agraphia caused by acute right parietal infarction.

Injury in the dominant language hemisphere typically leads to agraphia, however we report a patient with agraphia after injury to the right angular gyrus. A 71-year-old Korean woman presented with the complaint of an inability to write for the last 7 days. The patient had been illiterate for most of her life, but had started learning to write Hangul, the Korean alphabet, at a welfare center 3 years ago. On language screening she was unable to write although she could read, and other language functions showed no abnormalities. Brain MRI showed acute infarction in the right angular gyrus. Her writing patterns displayed features of surface agraphia, indicative of phoneme-to-grapheme conversion with phonetic writing of targets. Additionally, she manifested visual errors. A functional MRI indicated that her left hemisphere was language dominant. This patient experienced agraphia resulting from pure impairment of visuo-constructive function after acute infarction in the right angular gyrus.

Language-specific Dysgraphia in Korean Patients with Right Brain Stroke: Influence of Unilateral Spatial Neglect

The purpose of the present study was to investigate the relationship between Korean language-specific dysgraphia and unilateral spatial neglect in 31 right brain stroke patients. All patients were tested for writing errors in spontaneous writing, dictation, and copying tests. The dysgraphia was classified into visuospatial omission, visuospatial destruction, syllabic tilting, stroke omission, stroke addition, and stroke tilting. Twenty-three (77.4%) of the 31 patients made dysgraphia and 18 (58.1%) demonstrated unilateral spatial neglect. The visuospatial omission was the most common dysgraphia followed by stroke addition and omission errors. The highest number of errors was made in the copying and the least was in the spontaneous writing test. Patients with unilateral spatial neglect made a significantly higher number of dysgraphia in the copying test than those without. We identified specific dysgraphia features such as a right side space omission and a vertical stroke addition in Korean right brain stroke patients. In conclusion, unilateral spatial neglect influences copy writing system of Korean language in patients with right brain stroke.

Language-specific Dysgraphia in Korean Patients with Right Brain Stroke: Influence of Unilateral Spatial Neglect

The purpose of the present study was to investigate the relationship between Korean language-specific dysgraphia and unilateral spatial neglect in 31 right brain stroke patients. All patients were tested for writing errors in spontaneous writing, dictation, and copying tests. The dysgraphia was classified into visuospatial omission, visuospatial destruction, syllabic tilting, stroke omission, stroke addition, and stroke tilting. Twenty-three (77.4%) of the 31 patients made dysgraphia and 18 (58.1%) demonstrated unilateral spatial neglect. The visuospatial omission was the most common dysgraphia followed by stroke addition and omission errors. The highest number of errors was made in the copying and the least was in the spontaneous writing test. Patients with unilateral spatial neglect made a significantly higher number of dysgraphia in the copying test than those without. We identified specific dysgraphia features such as a right side space omission and a vertical stroke addition in Korean right brain stroke patients. In conclusion, unilateral spatial neglect influences copy writing system of Korean language in patients with right brain stroke.

Neural correlates of spelling difficulties in Alzheimer's disease.

Alzheimer's disease (AD) is associated with a general cognitive decline that affects the memory and language domains. Thus, an oral production deficit with a lexical-semantic origin has been widely observed in these patients. Their written production capacities, however, have been much less studied. We assessed the spelling abilities of 22 AD patients and a group of matched healthy controls with a test battery including written picture naming and word and pseudoword dictation tests, as well as text dictation and spontaneous writing tasks. The results of the AD patients in the discriminative tasks were then entered into voxel-based morphometry analyses along with their grey matter volumes. The patient group presented a selective impairment for word dictation, which contrasted with a spared capacity to spell pseudowords, and showed more difficulties for words with arbitrary and rule-based orthography. Moreover, they also produced less complete syntactic units in the spontaneous writing task. These results point out the lexical-semantic, as opposed to sublexical, nature of the spelling deficit associated to AD. In addition, we recognized a mainly left-lateralized cortical network, including areas in the posterior inferior temporal lobe and the superior region of the parietal cortex, which might be responsible for this impairment. Other regions, such as the putamen, were also associated to the deficit. The results of this study, hence, improve our understanding of the neuropsychological and neuroanatomical mechanisms that underlie the cognitive symptoms associated to AD.

Dyscalculia, dysgraphia, and left-right confusion from a left posterior peri-insular infarct.

The Gerstmann syndrome of dyscalculia, dysgraphia, left-right confusion, and finger agnosia is generally attributed to lesions near the angular gyrus of the dominant hemisphere. A 68-year-old right-handed woman presented with sudden difficulty completing a Sudoku grid and was found to have dyscalculia, dysgraphia, and left-right confusion. Magnetic resonance imaging (MRI) showed a focus of abnormal reduced diffusivity in the left posterior insula and temporoparietal operculum consistent with acute infarct. Gerstmann syndrome from an insular or peri-insular lesion has not been described in the literature previously. Pathological and functional imaging studies show connections between left posterior insular region and inferior parietal lobe. We postulate that the insula and operculum lesion disrupted key functional networks resulting in a pseudoparietal presentation.

Beyond the visual word form area: the orthography-semantics interface in spelling and reading.

Lexical orthographic information provides the basis for recovering the meanings of words in reading and for generating correct word spellings in writing. Research has provided evidence that an area of the left ventral temporal cortex, a subregion of what is often referred to as the visual word form area (VWFA), plays a significant role specifically in lexical orthographic processing. The current investigation goes beyond this previous work by examining the neurotopography of the interface of lexical orthography with semantics. We apply a novel lesion mapping approach with three individuals with acquired dysgraphia and dyslexia who suffered lesions to left ventral temporal cortex. To map cognitive processes to their neural substrates, this lesion mapping approach applies similar logical constraints to those used in cognitive neuropsychological research. Using this approach, this investigation: (a) identifies a region anterior to the VWFA that is important in the interface of orthographic information with semantics for reading and spelling; (b) determines that, within this orthography-semantics interface region (OSIR), access to orthography from semantics (spelling) is topographically distinct from access to semantics from orthography (reading); (c) provides evidence that, within this region, there is modality-specific access to and from lexical semantics for both spoken and written modalities, in both word production and comprehension. Overall, this study contributes to our understanding of the neural architecture at the lexical orthography-semantic-phonological interface within left ventral temporal cortex.