Neurocase The Neural Basis of Cognition ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/nncs20 Dorsal type letter-by-letter reading accompanying alexia with agraphia due to a lesion of the lateral occipital gyri Yasuhisa Sakurai , Emi Furukawa , Masanori Kurihara & Izumi Sugimoto To cite this article: Yasuhisa Sakurai , Emi Furukawa , Masanori Kurihara & Izumi Sugimoto (2020) Dorsal type letter-by-letter reading accompanying alexia with agraphia due to a lesion of the lateral occipital gyri, Neurocase, 26:5, 285-292, DOI: 10.1080/13554794.2020.1803922 To link to this article: https://doi.org/10.1080/13554794.2020.1803922 Published online: 17 Aug 2020. Submit your article to this journal Article views: 17 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=nncs20 NEUROCASE 2020, VOL. 26, NO. 5, 285–292 https://doi.org/10.1080/13554794.2020.1803922 Dorsal type letter-by-letter reading accompanying alexia with agraphia due to a lesion of the lateral occipital gyri Yasuhisa Sakurai a , Emi Furukawab,c, Masanori Kuriharaa,d and Izumi Sugimotoa,e a Department of Neurology, Mitsui Memorial Hospital, Tokyo, Japan; bDepartment of Nephrology, Mitsui Memorial Hospital, Tokyo, Japan; Department of Health Communication, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; dDepartment of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; eDepartment of Neurology, Toranomon Hospital Kajigaya, Kawasaki, Japan c ABSTRACT ARTICLE HISTORY We report a patient with alexia with agraphia accompanied by letter-by-letter reading after hemorrhage in the left middle and inferior occipital gyri that spared the angular gyrus and the fusiform gyrus. Kanji (Japanese morphograms) and kana (Japanese phonetic writing) reading and writing tests revealed that alexia with agraphia was characterized by kana-predominant alexia and kanji-predominant agraphia. This type of “dorsal” letter-by-letter reading is discernable from conventional ventral type letter-by-letter reading that is observed in pure alexia in that (1) kinesthetic reading is less effective, (2) kana or literal agraphia coexists, and (3) fundamental visual discrimination is nearly normal. Received 28 July 2019 Accepted 24 July 2020 Introduction Letter-by-letter reading has been thought to be characteristic of pure alexia (Coslett, 2011); however, some neuropsychologi­ cal studies have indicated that letter-by-letter reading is also observed in alexia with agraphia due to a lesion of the left posterior inferior temporal cortex (Rapcsak & Beeson, 2004; Sakurai, Takeuchi et al., 2000b). We begin with introducing the Japanese writing system. Two writing characters, kanji (morphograms of Chinese origin) and kana (Japanese phonetic syllabic writing simplified from Chinese characters) are used. Kanji are graphically complicated and have meaning and multiple pronunciations, whereas kana are graphically simple and have one pronunciation and usually no intrinsic meaning. Therefore, single-character kanji are words as well as letters, whereas single-character kana are usually letters, such as European alphabet. Both kanji and kana words consist of two or more kanji or kana characters and usually have one pronunciation. Thus, a kana reading impairment implies disturbance of letter/syllable identification or grapheme–phoneme conversion, whereas a kanji reading impairment implies disturbance of whole-word reading. Likewise, a kana writing impairment implies disturbance of letter/syllable recall or phoneme–grapheme conversion, whereas a kanji writing impairment implies disturbance of whole-word recall or spelling stroke (or letter) sequences. Kana are further divided into hiragana (a cursive form of kana that is normally used for grammatical morphemes, e.g., 走る [hashiru] meaning “run” is composed of 走 (kanji) and る (hir­ agana suffix denoting present tense), and katakana (a square form of kana used primarily for representing loan words, e.g., カ メラ [kamera], camera). The kana described in this paper denotes hiragana. Hiragana and katakana are allographic with each other having the same phonetic value but are CONTACT Yasuhisa Sakurai ysakurai-tky@umin.ac.jp © 2020 Informa UK Limited, trading as Taylor & Francis Group KEYWORDS Letter-by-letter reading; pure alexia; alexia with agraphia; kana; lateral occipital complex orthographically different (Sakurai et al., 2010), and have a mutual priming effect irrespective of the orthographic simi­ larity, e.g., か [ka], hiragana, and カ [ka], katakana (Kinoshita et al., 2019). We have previously reported two anatomically different types of pure alexia: fusiform type and posterior occipital type (Sakurai et al., 2006). Fusiform type pure alexia is characterized by kanji-predominant alexia that can be generalized to desig­ nate alexia for words, whereas posterior occipital type pure alexia is characterized by kana-specific alexia that can be gen­ eralized to designate alexia for letters. Letter-by-letter reading and the resulting word-length effect are observed in both types of pure alexia, although letter-by-letter reading is less pro­ nounced in the posterior occipital type (Sakurai et al., 2008, 2006). Our previous positron emission tomography study indi­ cated that the precise lesion location for fusiform type pure alexia was in the left mid-fusiform gyrus (Brodmann area (BA) 37) medial to the activated site (mid-fusiform/posterior inferior temporal gyri) in kanji word reading (Sakurai, Momose et al., 2000a). A later study indicated that the lesion location for posterior occipital type pure alexia was in the posterior fusi­ form/inferior occipital gyri (BA 18/19) (Sakurai et al., 2008), which was activated in covert reading of kana words (Sakurai, Momose et al., 2001b). In addition, we also found letter-by-letter reading in a patient with alexia with agraphia due to a lesion of the angular gyrus and the adjacent lateral occipital gyri (Sakurai et al., 2010). This lesion was clearly superior to those for pure alexia. That is, letter-by-letter reading in pure alexia is attribu­ table to damage to the left ventral temporal (anterior fusiform/ inferior temporal gyri) (Binder & Mohr, 1992), or lateral and ventral occipital gyri, including the occipitotemporal junction (Leff et al., 2001). We designate letter-by-letter reading in pure alexia as ventral type letter-by-letter reading, whereas letter-by- 286 Y. SAKURAI ET AL. letter reading due to a more superior lesion including the lateral occipital gyri is designated as dorsal type letter-byletter reading. Little is known about this dorsal type of letterby-letter reading. Herein, we report about a patient with letter- by-letter reading due to a lesion of middle and inferior occipital gyri that did not involve the angular gyrus and discuss the difference between this dorsal type of letter-by-letter reading and the conventional ventral type. Figure 1. MR images 14 days after onset. T1- and T2-weighted axial (upper and middle) and T2-weighted coronal (lower) images indicated a subcortical high-intensity area in the left middle and inferior occipital gyri that extended to the posterior horn of the lateral ventricle. The fusiform and angular gyri were spared. Figure 2. 99mTc- ECD-SPECT images at 19 days (upper panel) and 7 months (lower panel) after onset. Regional hypoperfusion is depicted in color. The red-to-bright yellow color gradient reflects increasing Z-scores. A focal reduction of the cerebral blood flow in the left lateral occipital gyri was noted at onset; the area with local maximum reduction was in the inferior occipital gyrus (Brodmann area (BA) 19, Montreal Neurological Institute (MNI) coordinates (−40, −76, 2)). The area with hypoperfusion did not involve the angular gyrus (arrow), but the posterior fusiform gyrus was affected. Over the course of 7 months, the hypoperfusion of the left lateral occipital gyri was limited to a small area: the local maximum reduction was in BA 19 (MNI coordinates (−36, −78, 2)). The imaging data were first normalized, smoothed, and adjusted to compare between laboratories with the easy Z-score Imaging System (eZIS version 3.4) (Matsuda et al., 2004), and constructed using a twosample t test: patient vs. healthy men aged 60–69 years (n= 18) (uncorrected P < 0.001) using Statistical Parametric Mapping (Friston et al., 1995) version 2 (SPM2) software. Areas with significant hypoperfusion were displayed on the standard surface brain images and the coronal section through the angular gyrus (y = −70 mm on the MNI coordinate). The vertical line denotes the z-axis (x = 0), and the horizontal line denotes the x-axis (z = 0) in the MNI space. NEUROCASE Case report A right-handed, 61-year-old man presented with headache, inability to read tickers on the television, and inability to operate an electronic calculator. He was a self-employed baker and had a graduate-level education. His medical history was notable for hypertension; however, he was not being treated with medica­ tion. After being referred to our hospital, he was admitted with a diagnosis of cerebral hemorrhage that was detected through computed tomography (CT) imaging. Neurological examination indicated 1) alexia and agraphia, 2) acalculia, and 3) visual extinction on the right. Magnetic resonance imaging (MRI) 14 days after symptom onset indicated an area of hyperintensity in the left posterior middle and inferior occipital gyri, which extended to the posterior horn of the lateral ventricle (Figure 1). The fusiform gyrus and the angular gyrus were spared. Single photon emission computed tomography with a 99mTcethylcysteinate dimer (99mTc- ECD-SPECT) performed 19 days after symptom onset indicated a focal reduction of the cerebral blood flow in the left lateral occipital gyri (Figure 2). The local peak reduction was in the inferior occipital gyrus (BA 19; Montreal Neurological Institute (MNI) coordinates: −40, −76, 2). The area with hypoperfusion did not involve the angular gyrus, but the posterior fusiform gyrus was affected. The patient underwent standard and special cognitive tests as detailed below at hospital admission and from 6 to 32 months later. The testing protocol was approved by the research ethics committee of our hospital, and written informed consent was obtained from the patient. Standard cognitive tests (Table 1) In the Wechsler Adult Intelligence Scale-III (WAIS-III) administered 2 weeks after admission, performance IQ was relatively lower than verbal IQ, and the processing speed was clearly low. Aphasia was not noted in the Western Aphasia Battery (WAB, Japanese edition) 7 days after onset, but reading was severely and writing was mildly impaired. The patient was unable to read words and sentences he had written. He could read kanji words but had difficulty reading kana characters. By contrast, he had difficulty writing kanji words, but he wrote kana words relatively easily; he was able to write 22 out of the 46 characters in the kana syllabary. He was able to read and write digits with ease. In all, kana-predominant alexia and kanji-predominant agraphia were noted. In the lexical decision task (to detect whether the stimulus character sequence is a real word or not) of the Test of Lexical Processing in Aphasia (TLPA) (I. Fujita et al., 2000), he achieved 72% (115/160) correct for the two-character kanji words and nonwords, suggesting that whole-word orthography of kanji words was relatively preserved. There was no frequency or ima­ geability effect by Fisher’s exact method. Special cognitive tests (Tables 2 and 4) Reading and writing test of 100 single-character kanji and kana transcriptions (Table 2, I) (Sakurai, Takeuchi et al., 2000b) Lists of 100 character kanji and the transcribed kana words were displayed on a separate A4 sheet. All of the kanji 287 Table 1. Scores for standard neuropsychological tests at disease onset. WAIS-III Verbal IQ 102 Digit span forward (raw score) 5 Performance IQ 82 Working memory 81 Processing speed 63 WAB Spontaneous speech Information content (/10) 10 Fluency (/10) 10 Naming total (/10) 9.1 Object naming (/60) 60 Repetition (/10) 10 Comprehension total (/10) 9.4 Reading total (/10) 2.49 Kanji reading (/6) 6 Kana reading (/6) 3 Writing total (/10) 7.95 Kanji writing (/6) 1 Kana writing (/6) 5 Calculation (/24) 20 Praxis (/10) rt. 10, lt. 10 TLPA Lexical decision of two-character kanji High-freq., high-image. words (/20) 16 High-freq., low-image. words (/20) 15 Low-freq., high-image. words (/20) 16 Low-freq., low-image. words (/20) 11 Nonwords (/80) 57 Lexical decision of three-character kana Words (/60) 24 Nonwords (/60) 19 WAIS-III, Wechsler Adult Intelligence Scale-III; WAB, Western Aphasia Battery; TLPA, Test of Lexical Processing in Aphasia; freq., frequency; image., imageable; rt., right; lt., left. characters are taught in the first 3 years of primary school in Japan. The patient was asked to write kanji, kana, then to read kanji, and kana in this order. Correct responses and time for reading were counted. Reading was more impaired in kana (P < 0.0001 by Fisher’s exact method), whereas writing was more impaired in kanji (P < 0.0001 by Fisher’s exact method). Errors were as follows: no response in kanji reading (10 out of 13 errors), phonological errors (phonemic paralexia; 52%), and no response (39%) in kana reading (Table 3A), no response in kanji writing, (94%) and phonological errors (phonemic para­ graphia) in kana writing (65%; Table 3B). Kinesthetic reading was effective only in some kanji characters (footnote (b) of Table 2). Reading test of kana single characters, two-character kanji words, three-character kana words and nonwords, five-character kana words and nonwords, and kanji transcriptions (Table 2, II, III) (Sakurai et al., 2010) Single-character kana were 46 letters of kana syllabary that were randomly listed on a sheet. High-familiarity three- (mean 5.98 on a seven-point rating scale) and five-character kana words were selected from research reports (Amano & Kondo, 2000; T. Fujita et al., 1991), and three- and five-character non­ words were made by changing the sequential order of kana characters, e.g., あした ([ashita], tomorrow) → たしあ ([tashia], nonword). Low-familiarity kana words (mean 4.20 on a seven-point rating scale) (Amano & Kondo, 2000), twocharacter kanji words transcribed from the high-familiarity 288 Y. SAKURAI ET AL. Table 2. Scores for the special neuropsychological tests: reading and writing. Onset 6–30 months Controls a Mean Mean time score (SD) (SD) I. Reading and writing (100 single-character kanji and kana transcription), raw score and time (percentile) (follow-up 6 months after onset) Kanji reading (/100) 87 (<1) b 100 (>9) 99.6 (1.2) 1 min 32 s (32 s) 7 min 1 2 min 31 s (>99) s (96) Kana reading (/100) 12 (<1) b 95 (35) 99.6 (0.5) 1 min 13 s (24 s) 16 min 1 6 min 8 s (>99) s (>99) Kanji writing (/100) 32 (<1) 57 (<1) 95.9 (3.0) 10 min 11 s (136 s) 11 min 16 12 min 37 s (61) s (91) Kana writing (/100) 80 (<1) 97 (<1) 99.3 (0.9) 8 min 7 s (107 s) 9 min 57 8 min 17 s s (87) (60) II. Reading (100 two-character kanji words, three-character kana words and three-character kana nonwords), correct responses and time (follow-up 7–8 months after onset) Two-character kanji 30 (<1) 98 (<11) 99.3 (0.8) 1 min 20 words (/100) s (14 s) 8 min 50 2 min 23 s (>99) s (>99) Three-character kana 54 (<1) 91 (<1) 98.3 (1.6) 2 min 1 words (hf) (/100) s (37 s) 13 min 41 4 min 11 c s (>99) s (>99) 2 (<1) Three-character kana 86 (<1) 96.6 (2.0) 2 min 28 s (41 s) words (lf) (/100) 16 min 22 not recorded s (>99) Three-character kana 8 (<1) 84 (<1) 97.8 (1.3) 2 min 1 nonwords (/100) s (37 s) 16 min 30 5 min 31 s (>99) s (>99) III. Reading (46 single-character kana, 50 five-character kana words and fivecharacter kana nonwords), correct responses and time (follow-up 7–8 months after onset) Single-character kana 24 (<1) 41 (<1) 45.7 (0.6) 24 s (4 s) (/46) 4 min 14 47 s (>99) s (>99) c Five-character kana 0 (<1) 48 (<1) 49.5 (0.5) 1 min 24 words (/50) s (32 s) 12 min 25 3 min 3 s (>99) s (>99) c Kanji transcription (/50) 12 (<1) 49 (10–50) 49.4 (0.6) 54 s (15 s) 8 min 23 59 s (73) s (>99) Five-character kana 0 (<1) 32 (<1) 47.0 (2.1) 2 min 16 nonwords (/50) s (33 s) 13 min 47 5 min 24 s (>99) s (>99) IV. Writing (50 three- and five-character kana words and nonwords), raw score and time (percentile) (follow-up 32 months after onset) Three-character kana 47 (<1) d 47 (<1) 49.7 (0.9) 3 min 50 words (/50) s (66 s) 3 min 50 3 min 38 s (51) s (48) Three-character kana 42 (<1) d 47 (5) 48.9 (1.3) 4 min 6 s (76 s) nonwords (/50) 4 min 12 3 min 59 s (49) s (48) Five-character kana 36 (<1) d 47 (<1) 49.5 (0.7) 6 min 4 s (89 s) words (/50) 5 min 45 5 min 25 s (71) s (60) Five-character kana 19 (<1) d 32 (11) 36.2 (5.3) 7 min 49 s (117 s) nonwords (/50) 8 min 6 s 8 min 59 s a Healthy controls: Reading and writing (100 words), n = 11 (mean, 68 years old) (Sakurai, Takeuchi, et al., 2000b); Reading (II, III), n = 11 (mean, 73 years old) (Sakurai et al., 2006); Writing (IV, three-character words), n = 11 (mean, 73 years old) (Sakurai et al., 2010); Writing (IV, five-character words), n= 10 (mean, 74 years old) (Sakurai et al., 2018); all with 9 or more years of education and no past history of neurologic illness. b Kinesthetic reading was successful in 14/22 trials for kanji and 2/29 trials for kana. c Mean time for reading kana in the patient (and the healthy controls) was as follows: single-character, 5.52 (0.53) s/character; three-character words, 8.21 (1.22) s/word; and five-character words, 14.90 (1.70) s/word. d Writing errors consisted of 1 phonological, 2 phonological/visual, for the threecharacter words; 7 phonological, 1 phonological/visual, for the three-character nonwords; 6 phonological, 5 phonological/visual, 3 allographic, for the fivecharacter words; and 24 phonological, 1 phonological/visual, 3 transposition (changing the sequence of two consecutive characters), 3 partial, for the fivecharacter nonwords. For the explanation of other errors, see the footnote of Table 3B. hf, high familiarity; lf, low familiarity. kana words, e.g., あした → 明日 ([ashita], tomorrow), and various kanji–kana compound words partially transcribed from the five-character kana words (kanji words with kana suffixes), e.g., なつやすみ → 夏休み [natsuyasumi], summer vacation, were also provided on a separate sheet. The patient was asked to read the stimulus characters successively from the beginning. Reading was impaired even at the level of single-character kana. Letter-by-letter reading was observed in three- and five-character kana words and nonwords. A word-length effect was observed: time for reading elevated from 5.52 s/character for the single-character to 14.90 s/word for the five-character words (footnote (c) of Table 2). Word-byword reading (reading one word at a time with much reading pause) was also observed in three-character kana words. Reading of two-character kanji and kanji transcription of fivecharacter kana words were also disturbed. The patient com­ plained that he could not read kanji words because he did not understand the meaning or remember the reading even if he understood the meaning. Low-familiarity three-character kana words were read as poorly as three-character kana nonwords, suggesting that lexicality had little effect on the reading of low-familiarity words. Neither five-character kana words nor five-character kana nonwords were read, suggesting that sequential letter recognition was not available in fivecharacter kana words and nonwords. Errors consisted of no response in two-character kanji (91%) and phonological errors (phonemic paralexia) in three-character kana words (83%) and nonwords (75%) (Table 3C). Writing test of three-character kana words and nonwords and five-character kana words and nonwords (Table 2, IV) (Sakurai et al., 2018) Test items were the anterior half of the 100 three-character word and nonword reading tests and all the 50 five-character word and nonword reading tests (Table 2, II, III). The patient wrote from dictation these words and nonwords separately on a sheet. Writing was more impaired for five-character words and non­ words than for three-character words and nonwords (wordlength effect), and in nonwords than words for both three and five characters (lexicality effect). Phonological and phonological/ visual (one kana character was changed to another visually similar character) errors accounted for most errors (100% in three-character words and nonwords, 79% in five-character NEUROCASE Table 3A. Types of reading errors in 100 single-character kanji and kana tran­ scriptions test (Test I in Table 2). Onset 6 months Kanji No response Visual Unrelated 10 2 1 0 0 0 Kana No response Phonological Phonological/visual Partial Unrelated 35 46 3 3 1 0 3 1 0 0 Visual: changing the kanji reading to the reading of another kanji with a visual resemblance to the correct answer, e.g., 休 ([yasumu], rest) → read as 体 ([karada], body); unrelated: changing to the reading of another word that has no phonological or orthographical similarity; phonological: one or more char­ acters of a kana word were substituted for other kana (phonemic paralexia), e.g., あめ ([ame], rain) → あお ([ao], blue); phonological/visual: one kana character was pronounced incorrectly for a visually similar character, e.g., い わ ([iwa], rock) → いつ ([itsu], when); partial response: one or more characters of a kana word were not read. Table 3B. Types of writing errors in 100 single-character kanji and kana transcrip­ tions test (Test I in Table 2). Kanji No response Visual Constructional Unrelated Neographism Kana No response Partial Phonological Phonological/visual Allographic Onset 6 months 64 1 1 2 0 41 0 1 0 1 1 1 13 4 1 289 Table 3C. Types of reading errors in two-character kanji word, three-character kana word (high familiarity), and three-character kana nonword tests (Tests II and III in Table 2). Two-character kanji word No response Partial Lexical Unrelated Three-character kana word (hf) Phonological No response Lexical Unrelated Three-character kana nonword Phonological Phonological/visual No response Partial Lexical Onset 6 months 64 4 0 2 0 0 2 0 38 7 0 1 8 0 1 0 69 3 13 7 0 14 1 0 0 1 Partial: only one character was read correctly; lexical: changing to another word that contains the same kanji or kana characters of the correct word, e.g., 範囲 ([haNi], extent) → read as 模範 ([mohan], model); うてん ([uten], rain) → read as うんてん ([unten], driving); unrelated: changing to the reading of another word that has no phonological or orthographical similarity; phonological/visual: one character is read as a visually similar character, and another character is pronounced incorrectly, e.g., うくつ ([ukutsu], nonword) → うかう ([ukau], nonword); for other errors, see the footnote of Table 3A. hf, high familiarity. Table 4. Scores for the special neuropsychological tests: digit span, calculation, and visual discrimination. Controlsa Onset 9–12 months Mean score (SD) Digit span forward (percentile) (follow-up 12 months after onset)b Auditory digit span 5.0 (45) 4.8 (33) 5.28 (1.15) Auditory letter span 4.2 (7) 3.8 (<1) 4.9 (0.74) Visual digit span 5.0 (45) 4.4 (11) 5.38 (1.34) Visual letter span < 2.0 (<1) 4.2 (6) 5.2 (1.07) Visual memory span (WMS-R) 5.0 (56) 7.0 (98) 5 (56%ile)c 0 0 1 2 0 Visual: substitution of another kanji visually similar to the target character, e.g., 指 ([yubi], finger) → 脂 ([abura], fat); constructional: omission or addition of a component of a kanji, e.g., 左 ([hidari], left) → (nonword); unrelated: substitution of another kanji that has no visual, semantic, or phonological similarity to the correct answer; partial: one or more characters of a kana word were not written; phonological: one or more characters of a kana word were substituted for other kana (phonemic paragraphia), e.g., いぬ ([inu], dog) → いむ ([imu], detest); phonological/visual: changing one character to another visually similar character, e.g., くろい ([kuroi], black) → くるい ([kurui], aberration); allographic: one or more kana (more precisely hiragana, a cursive form of kana that is normally used for grammatical morphemes) characters were substituted for katakana (a square form of kana that is used primarily for representing loan words) characters, e.g., くる ([kuru], come) → くル ([kuru], hiragana-katakana). Calculation, raw score (percentile) (follow-up 9 months after onset) Mental arithmetic (/40) 23 (<1) 32 (1) 36.25 (2.73) Dictated calculation (/40) 27 (<1) 37 (1) 39.25 (0.96) Scientific calculator (/40) 40 (>18) 40 (>18) 39.83 (0.97) Visual discrimination test (follow-up 12 months after onset) Line length (/12) 11 (<28) 12 (>36) Circle size (/12) 12 (1–100) 12 (1–100) Parallel line (/12) 12 (1–100) 12 (1–100) Circle-oval (/12) 10 (<10) 11 (19–54) Square-rectangle (/12) 12 (>81) 12 (>81) Vertical point location (/12) 12 (>18) 12 (>18) Horizontal point location (/12) 12 (>18) 12 (>18) Distortion of a square (/12) 12 (>27) 12 (>27) Angle (/12) 12 (>18) 12 (>18) 11.67 (0.49) 12.00 (0.00) 12.00 (0.00) 11.25 (0.75) 10.75 (1.06) 11.83 (0.39) 11.67 (0.89) 11.67 (0.65) 11.75 (0.62) a words, and 81% in five-character nonwords). Three allographic errors (changing one kana character into another form of kana [katakana], see footnote of Table 3B) were observed in fivecharacter words, and three transposition errors (changing the sequence of two consecutive characters) were observed in fivecharacter nonwords (footnote (d) of Table 2). Modality-specific digit span and letter/character span (Table 4) (Sakurai et al., 2018) Digit or letter sequences were presented auditorily (usual digit or letter span forward, one digit or letter/s) and visually using a laptop with a presentation duration of 500 ms and an interval of 500 ms. To investigate the effect of spatial working memory, we also administered visual memory span of the Wechsler Healthy controls: digit span, n = 10 (mean, 58 years old) (Sakurai et al., 2018); calculation, n = 12 (mean, 67 years old) (Sakurai et al., 2018); visual discrimina­ tion, n = 12 (mean, 74 years old) (Sakurai et al., 2016); all had 9 or more years of education and no past history of neurologic illness. b In the visual or auditory digit span test, five sets of stimuli were given for each digit sequence, and 0.2 points were given for a correct response. In the visual memory span test, two sets of stimuli were supplied for each dot sequence, and 0.5 points were given for a correct response. c Based on the Manual for the Wechsler Memory Scale-Revised (WMS-R, Japanese edition), n = 50 (age range, 55–64 years). WMS-R: Wechsler Memory Scale-Revised. Memory Scale-Revised. The digit span forward score, either auditory or visual, was approximately 5, within normal range. Letter/character span forward score was slightly lower, ≤4. The visual memory span score was 5, average level. 290 Y. SAKURAI ET AL. Calculation test (Table 4) (Sakurai et al., 2018) A total of 40 calculations, consisting of an equal number of addition, subtraction, multiplication, and division tasks, were performed. The examiner first read a calculation task, and then the patient conducted mental arithmetic, dictated calculation, and calculation with a scientific calculator. Mental arithmetic and dictated calculation were both impaired. Since dictated writing was complete, incorrect answers in dictated calculation suggested anarithmetia (impairment of the calculation process per se). In addition, the difference between mental arithmetic and dictated calculation scores reflected the involvement of reduced working memory. Visual discrimination test (Table 4) (Sakurai et al., 2016; Sakurai, Ichikawa et al., 2001a) Two sets of line-drawings with slightly different lengths, sizes, shapes, spatial locations, etc. were provided. The patient was asked whether the two drawings on a card were the same or different and, if different, to explain the difference (For exam­ ples of the stimulus figures, see Sakurai et al., 2016). Results suggested that fundamental visual discrimination, such as line length, shape size, shape difference, horizontal distance, and slope, was nearly normal. Recovery of function over time Alexia of kanji and kana recovered within six months after hospital admission, although the patient still read kanji and kana characters slowly. Agraphia of kana recovered substan­ tially, but the patient wrote 20 out of the 46 kana syllabary even at three and a half years after onset. On the other hand, kanji writing recovered slightly. Digit and letter span scores had not changed by 1 year after admission, except for visual letter span, whereas the visual memory span score improved from 5 to 7. Mental arithmetic and dictated calculation recov­ ered, but not to within normal range by 9 months after admis­ sion. Because digit span had rarely changed, this recovery was not due to the improvement of verbal short-term memory but that of the arithmetic skill itself and spatial working memory (to maintain the alignment of digits), as demonstrated by the increase of visual memory span. He returned to work five months after discharge. Of note is that he found it difficult to knead the bread well and divide it into two halves accu­ rately, which he had done almost automatically before the disease onset. As a result, he had to weigh the divided part on a saucer scale. This disorder lasted for six months. On 99mTcECD-SPECT performed 7 months after onset, hypoperfusion of the left lateral occipital gyri was limited to a small area (Figure 2). Discussion The patient in this case report presented with alexia with agraphia, more precisely kana-predominant alexia with letterby-letter reading, lexical agraphia of kanji, and literal and allo­ graphic agraphia (Rapcsak & Beeson, 2002) of kana, accompa­ nied by acalculia and working memory impairment. Singlecharacter kana reading was impaired, and a word-length effect was evident. Although single-character kanji reading was relatively preserved, whole-word reading of two-character kanji was severely impaired. This is either because orthography of a two-character word was disrupted or orthography did not connect with the phonological lexicon. The latter is more con­ cerned because the patient achieved 72% correct in the lexical decision task for kanji (Table 1). Fundamental visual discrimina­ tion was preserved. The alexia with agraphia resolved to lexical agraphia for kanji and phonological agraphia (selective impair­ ment of nonword spelling) for kana over the course of 32 months. Alexia with agraphia due to an angular gyrus lesion has been previously described (Benson, 1985). Angular alexia with agra­ phia typically presents with lexical agraphia (selective impair­ ment of irregular word writing), corresponding to Japanese kanji agraphia. In addition, in Japanese cases of angular alexia with agraphia, alexia of kana also occurs (Kawamura, 1990; Miyake & Tanaka, 1992). However, limited damage to the angu­ lar gyrus does not cause alexia, but rather isolated kanji agra­ phia (Sakurai, Takeuchi et al., 2000b). Thus, it was assumed that the alexia in angular alexia with agraphia was the result of lesion extension into the adjacent lateral occipital gyri. A subsequent case report indicated that kana-predominant alexia with agraphia became evident only after a new infarction that involved the lateral occipital gyri after an old infarction in the angular gyrus (Kuriyama et al., 2006). The patient presented here directly demonstrates that alexia arises from a lesion of the middle and inferior occipital gyri and manifests as letter-by-letter reading. The lesion location is simi­ lar to that of posterior type of pure alexia for kana (Oishi et al., 2018; Sakurai, Ichikawa et al., 2001a; Sakurai et al., 2008); how­ ever, the posterior fusiform gyrus was not structurally involved in the present patient (although it may have been functionally affected in the acute phase ECD-SPECT). It should be noted that the MNI coordinates in the inferior occipital gyrus for local maximum blood flow reduction were (−40, −76, 2) in the pre­ sent patient, 14 mm above the peak reduction site (−38, −80, −12) observed in the posterior fusiform/inferior occipital gyri (Sakurai et al., 2008) for the ventral posterior occipital type of letter-by-letter reading. This anatomical difference influenced semiology, as described below. Characterization of dorsal type of letter-by-letter reading as compared with ventral type (Table 5) Letter-by-letter reading in the present patient did not differ from conventional ventral letter-by-letter reading in its charac­ teristic features; that is, a word-length effect and impaired letter identification were noted (Sakurai et al., 2006). However, there were some differences between dorsal and ventral letter-byletter reading. One is that kinesthetic facilitation was less func­ tional in our patient. This is probably because the hematoma was extensive enough to interrupt kinesthetic information tra­ veling from the parietal somatosensory cortex to the ventral occipitotemporal area. In this regard, previous studies have reported that a subregion of the lateral occipital complex (LOC) is activated in tactile naming and object naming (Amedi, Jacobson, Hendler, Malach & Zohary, 2002; Amedi et al., 2001); it is possible to assume that damage to the left LOC interfered with kinesthetic reading. The fact that the NEUROCASE Table 5. Comparison of two types of letter-by-letter reading. Letter-by-letter reading Word-length effect Single-letter identification Kinesthetic reading Reading impairment Writing impairment Visual discrimination Lesion location Ventral type present present impaired effective Kanji > < Kanaa Words > < Letters Kanji Words sl. impaired (post O type) mid-Fu (fusiform type) post Fu/inf O (post O type) Dorsal type present present impaired less effective Kana > Kanjib Letters > Words Kanji > Kanac Words > Letters normal mid and inf O a Kanji (or word) reading is more impaired than kana (or letter) reading (fusiform type) or kana (or letter) reading is more impaired than kanji (or word) reading (posterior occipital type). b Kana (or letter) reading is more impaired than kanji (or word) reading. c Kanji (or words) writing is more impaired than kana (or letter) writing. sl., slightly; post O, posterior occipital; mid-Fu, mid-fusiform gyrus; mid and inf O, middle and inferior occipital gyri; post Fu, posterior fusiform gyrus. patient had difficulty kneading the bread and dividing it into two halves suggests evidence of tactile–visual disconnection. The second difference is that our patient had difficulty writ­ ing kana characters, which is not observed in ventral pure alexia (Sakurai et al., 2006). However, kana writing is slightly impaired in alexia with agraphia from a posterior inferior temporal cortex (BA 37, more precisely mid-fusiform/posterior inferior temporal gyri) lesion (Kawamura, 1990; Sakurai, Takeuchi et al., 2000b; Soma et al., 1989), the location of which is lateral to that of fusiform type pure alexia (Sakurai et al., 2006). We thought that visual images of kana or letters are widely distributed in the ventral occipitotemporal area and the lateral occipital gyri and are used for both phonology (grapheme–phoneme conversion) and orthography (whole-word recognition) (Sakurai, 2004). In writing from dictation, visual images of kana are sent to the parietal graphemic area to output visuokinesthetic pattern of the kana character to the frontal motor hand area (Sakurai et al., 2007). The existence of kana agraphia or literal agraphia in general implicates interruption of kana (or letter) visual images traveling from the ventral occipitotemporal area or lateral occi­ pital gyri to the parietal and frontal lobes. Damage to the lateral occipital gyri (demonstrated by MRI) in the patient presented here may have contributed to his kana agraphia. Because the mid-fusiform/posterior inferior temporal gyri (BA 37) were spared damage both on the MRI and ECD-SPECT images, it is less probable that this area was involved in the kana agraphia. The third difference is that fundamental visual discrimina­ tion was preserved in our patient, whereas it was slightly impaired in the ventral posterior occipital type letter-by-letter reading patients (Sakurai et al., 2008). It is possible that deficits of fundamental visual discrimination affect kana character iden­ tification in the ventral posterior occipital type letter-by-letter reading whereas grapheme–phoneme conversion is more con­ cerned in the dorsal type letter-by-letter reading. In summary, coexisting agraphia and normal visual discrimi­ nation distinguish the dorsal type of letter-by-letter reading from the ventral type. The distinction between dorsal and ventral letter-by-letter reading is clinically important because the dorsal type implies the involvement of the dorsal part of the lateral occipital gyri and requires rehabilitation not only for alexia but also for agraphia. As the lateral occipital gyri are 291 rarely damaged in cerebrovascular disease, further study is needed to elucidate the functional role of this area. Disclosure statement No potential conflict of interest was reported by the authors. ORCID Yasuhisa Sakurai http://orcid.org/0000-0002-6992-6747 References Amano, S., & Kondo, T. (2000). NTT data base series. Lexical properties of Japanese. First period. Sanseido. Amedi, A., Jacobson, G., Hendler, T., Malach, R., & Zohary, E. (2002). Convergence of visual and tactile shape processing in the human lateral occipital complex. Cerebral Cortex, 12(11), 1202–1212. https://doi.org/10. 1093/cercor/12.11.1202 Amedi, A., Malach, R., Hendler, T., Peled, S., & Zohary, E. (2001). Visuo-haptic object-related activation in the ventral visual pathway. Nature Neuroscience, 4(3), 324–330. https://doi.org/10.1038/85201 Benson, D. F. (1985). Alexia. In J. A. M. Frederiks (Ed.), Handbook of clinical neurology (Vol. 45, pp. 433–455). Elsevier. Binder, J. R., & Mohr, J. P. (1992). The topography of callosal reading path­ ways. A case-control analysis. Brain, 115(6), 1807–1826. https://doi.org/ 10.1093/brain/115.6.1807 Coslett, H. B. (2011). Acquired dyslexia. In K. M. Heilman & E. Valenstein (Eds.), Clinical neuropsychology (5th ed., pp. 115–129). Oxford University Press. Friston, K. J., Holmes, A. P., Worsley, K. J., Poline, J.-P., Frith, C. D., & Frackowiak, R. S. J. (1995). Statistical parametric maps in functional imaging: A general linear approach. Human Brain Mapping, 2(4), 189–210. https://doi.org/10.1002/hbm.460020402 Fujita, I., Monoi, H., Okudaira, N., Ueda, M., Ono, K., & Shimogaki, Y. (2000). Developing a Test of Lexical Processing in Aphasia (TLPA). Onsei Gengo Igaku = the Japan Journal of Logopedics and Phoniatrics, 41(2), 179–202. https://doi.org/10.5112/jjlp.41.179 Fujita, T., Saito, S., & Takahashi, M. (1991). The familiarity values of Japanese five-letter nouns. Memories of Kyoto Tachibana Women’s University, 18, 79–93. Kawamura, M. (1990). Localization and symptomatology of pure alexia, pure agraphia and alexia with agraphia. Shinkei Shinrigaku = the Japanese Journal of Neuropsychology, 6(1), 16–23. http://www.neuropsy chology.gr.jp/journal/archive/1990_06_01_03.pdf Kinoshita, S., Schubert, T., & Verdonschot, R. G. (2019). Allograph priming is based on abstract letter identities: Evidence from Japanese kana. Journal of Experimental Psychology: Learning, Memory, and Cognition, 45(1), 183–190. https://doi.org/10.1037/xlm0000563 Kuriyama, N., Suzuki, N., & Matsuda, M. (2006). A case of alexia with agraphia caused by the re-infarct in left lateral occipital gyrus. Rinsho Shinkeigaku = Clinical Neurology, 46(7), 505–509. Leff, A. P., Crewes, H., Plant, G. T., Scott, S. K., Kennard, C., & Wise, R. J. (2001). The functional anatomy of single-word reading in patients with hemi­ anopic and pure alexia. Brain, 124(3), 510–521. https://doi.org/10.1093/ brain/124.3.510 Matsuda, H., Mizumura, S., Soma, T., & Takemura, N. (2004). Conversion of brain SPECT images between different collimators and reconstruction processes for analysis using statistical parametric mapping. Nuclear Medicine Communications, 25(1), 67–74. https://doi.org/10.1097/ 00006231-200401000-00010 Miyake, H., & Tanaka, T. (1992). A case of alexia in kana and agraphia in kanji with the left temporo-parietal subcortical hematoma. Shitsugosho Kenkyu = Higher Brain Function Research, 12(1), 1–9. https://doi.org/10. 2496/apr.12.1 Oishi, Y., Nagasawa, H., & Suzuki, K. (2018). The case study of a patient with alexia and agraphia who can read kana words but not kana single letters. 292 Y. SAKURAI ET AL. Shinkei Shinrigaku = the Japanese Journal of Neuropsychology, 34(1), 63–73. https://doi.org/10.20584/neuropsychology.17014 Rapcsak, S. Z., & Beeson, P. M. (2002). Neuroanatomical correlates of spelling and writing. In A. E. Hillis (Ed.), The handbook of adult language disorders. Integrating cognitive neuropsychology, neurology, and rehabilitation (pp. 71–99). Psychology Press. Rapcsak, S. Z., & Beeson, P. M. (2004). The role of left posterior inferior temporal cortex in spelling. Neurology, 62(12), 2221–2229. https://doi. org/10.1212/01.WNL.0000130169.60752.C5 Sakurai, Y. (2004). Varieties of alexia from fusiform, posterior inferior tem­ poral and posterior occipital gyrus lesions. Behavioural Neurology, 15 (1–2), 35–50. https://doi.org/10.1155/2004/305194 Sakurai, Y., Asami, M., & Mannen, T. (2010). Alexia and agraphia with lesions of the angular and supramarginal gyri: Evidence for the disruption of sequential processing. Journal of the Neurological Sciences, 288(1–2), 25–33. https://doi.org/10.1016/j.jns.2009.10.015 Sakurai, Y., Furukawa, E., Kurihara, M., & Sugimoto, I. (2018). Frontal phono­ logical agraphia and acalculia with impaired verbal short-term memory due to left inferior precentral gyrus lesion. Case Reports in Neurology, 10 (1), 72–82. https://doi.org/10.1159/000487849 Sakurai, Y., Hamada, K., Tsugawa, N., & Sugimoto, I. (2016). Ventral simulta­ nagnosia and prosopagnosia for unfamiliar faces due to a right posterior superior temporal sulcus and angular gyrus lesion. Neurocase, 22(1), 122–129. https://doi.org/10.1080/13554794.2015.1066827 Sakurai, Y., Ichikawa, Y., & Mannen, T. (2001a). Pure alexia from a posterior occipital lesion. Neurology, 56(6), 778–781. https://doi.org/10.1212/WNL. 56.6.778 Sakurai, Y., Momose, T., Iwata, M., Sudo, Y., Ohtomo, K., & Kanazawa, I. (2000a). Different cortical activity in reading of Kanji words, Kana words and Kana nonwords. Brain Research Cognitive Brain Research, 9(1), 111–115. https://doi.org/10.1016/S0926-6410(99)00052-X Sakurai, Y., Momose, T., Iwata, M., Sudo, Y., Ohtomo, K., & Kanazawa, I. (2001a). Cortical activity associated with vocalization and reading proper. Brain Research Cognitive Brain Research, 12(1), 161–165. https:// doi.org/10.1016/S0926-6410(01)00023-4 Sakurai, Y., Onuma, Y., Nakazawa, G., Ugawa, Y., Momose, T., Tsuji, S., & Mannen, T. (2007). Parietal dysgraphia: Characterization of abnormal writing stroke sequences, character formation and character recall. Behavioural Neurology, 18(2), 99–114. https://doi.org/10.1155/2007/ 906417 Sakurai, Y., Takeuchi, S., Takada, T., Horiuchi, E., Nakase, H., & Sakuta, M. (2000b). Alexia caused by a fusiform or posterior inferior temporal lesion. Journal of the Neurological Sciences, 178(1), 42–51. https://doi.org/10. 1016/S0022-510X(00)00363-4 Sakurai, Y., Terao, Y., Ichikawa, Y., Ohtsu, H., Momose, T., Tsuji, S., & Mannen, T. (2008). Pure alexia for kana. Characterization of alexia with lesions of the inferior occipital cortex. Journal of the Neurological Sciences, 268(1–2), 48–59. https://doi.org/10.1016/j.jns. 2007.10.030 Sakurai, Y., Yagishita, A., Goto, Y., Ohtsu, H., & Mannen, T. (2006). Fusiform type alexia: Pure alexia for words in contrast to posterior occipital type pure alexia for letters. Journal of the Neurological Sciences, 247(1), 81–92. https://doi.org/10.1016/j.jns. 2006.03.019 Soma, Y., Sugishita, M., Kitamura, K., Maruyama, S., & Imanaga, H. (1989). Lexical agraphia in the Japanese language. Pure agraphia for Kanji due to left posteroinferior temporal lesions. Brain, 112(6), 1549–1561. https:// doi.org/10.1093/brain/112.6.1549