A review on alexia rare syndrome

Prema B; Asma Parveen SK; Prapurna Chandra Yadala; Suchithra M

doi:10.37022/jis.v8i3.125

B. Prema B.Pharmacy 4th year, Ratnam institute of pharmacy, Pidhapulour(V), Muthukur(M), SPSR Nellore Dt.524346, Andhrapradesh.
SK. Asma Parveen Department of Pharmaceutical Analysis, Ratnam Institute of Pharmacy, Pidathapolur (V), Muthukur(M), SPSR Nellore Dt.524346, Andhrapradesh.
Yadala Prapurna Chandra Principal and Professor, Department of Pharmacology, Ratnam Institute of Pharmacy, Pidathapolur (V & P), Muthukur (M), SPSR Nellore District-524 346, Andhra Pradesh.
M. Suchithra Professor & HOD,Department of Pharmaceutical Analysis, Ratnam Institute Of Pharmacy, Pidathapolur(V&P), Muthukur(M), SPSR Nellore District-524346, Andhra Pradesh.

DOI https://doi.org/10.37022/jis.v8i3.125

Abstract

Alexia is a rare neurological disorder characterized by the acquired inability to read, often accompanied by spared writing and speech abilities. This condition primarily arises from focal brain lesions affecting regions critical for visual word recognition and reading, including the occipital cortex, corpus callosum, and angular gyrus. The disorder manifests in several clinical subtypes such as pure alexia, alexia with agraphia, frontal alexia, and posterior alexia, each associated with distinct neuroanatomical and pathological features. Etiologies range from vascular insults like ischemic stroke to traumatic brain injury, neurodegenerative diseases including Alzheimer’s, as well as infectious, neoplastic, and demyelinating conditions. Clinically, alexia presents with deficits in word recognition and reading fluency while often preserving the ability to write and speak, accompanied by additional neurological symptoms such as hemianopia and aphasia. Diagnostic evaluation integrates detailed clinical and neuropsychological assessments with advanced neuroimaging techniques, including MRI, fMRI, and diffusion tensor imaging (DTI), to localize lesions and understand underlying mechanisms. Theoretical models of visual word processing and hemispheric language dominance provide frameworks for understanding alexia’s cognitive underpinnings. Therapeutic interventions emphasize speech and language therapy supported by emerging digital tools, with novel approaches including neuromodulation via transcranial magnetic stimulation and direct current stimulation showing promise. Recent advances in connectomics, machine learning, and brain-computer interfaces offer innovative avenues for rehabilitation and recovery. Despite progress, challenges such as underdiagnosis, limited access to specialized care, and lack of standardized protocols remain. This review synthesizes current knowledge on alexia, integrating neurobiological and behavioural perspectives, and highlights directions for future research to enhance diagnosis, treatment, and patient outcomes.

Keywords: Alexia, pure alexia, neuroanatomy, reading disorders, rehabilitation, neuromodulation

References

1. Barbosa AC. Alexia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Mar 3 [cited 2025 Oct 11]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557669/
2. Alduais A. Neuropsychological diagnosis and assessment of alexia. Front Psychol. 2024;15:622.
3. Dejerine J. Anatomie des centres nerveux. Vol. 2. Paris: Rueff; 1892.
4. Geschwind N. The Herner’s fasciculus and its role in conduction aphasia. Arch Neurol. 1965;12(1):4–7.
5. EyeWiki. Alexia without agraphia [Internet]. 2024 Nov 25 [cited 2025 Oct 11]. Available from: https://eyewiki.org/Alexia_without_Agraphia
6. Cureus. Alexia without agraphia: a rare entity [Internet]. 2017 Jun 1 [cited 2025 Oct 11]. Available from: https://www.cureus.com/articles/7391-alexia-without-agraphia-a-rare-entity
7. MD Searchlight. Alexia [Internet]. 2024 Dec 18 [cited 2025 Oct 11]. Available from: https://mdsearchlight.com/neurology/alexia/
8. MedLink. Alexia [Internet]. 2025 May 28 [cited 2025 Oct 11]. Available from: https://www.medlink.com/articles/alexia
9. Oxford Academic. Aphasia: a clinical perspective – Alexia [Internet]. 2025 [cited 2025 Oct 11]. Available from: https://academic.oup.com/book/53543/chapter/422110464
10. Hubel DH, Wiesel TN. Receptive fields, binocular interaction and functional architecture in the cat’s visual cortex. J Physiol (Lond). 1962;160:106–154.
11. Dehaene S, Cohen L. The unique role of the visual word form area in reading. Trends Cogn Sci. 2011;15(6):254–262.
12. Cohen L, Dehaene S. Specialization within the ventral stream: the case for the visual word form area. Neuroimage. 2004;22(1):466–476.

13. Gaillard R, Naccache L, Pinel P, et al. Direct intracranial, fMRI, and lesion evidence for the causal role of the left mid-fusiform gyrus in reading. Neuron. 2006;50(2):191–204.
14. Price CJ. The anatomy of language: a review of 100 fMRI studies. Cereb Cortex. 2012;22(1):200–210.
15. Pugh KR, Mencl WE, Shaywitz BA, et al. The angular gyrus in reading: converging evidence from functional imaging studies. Ann N Y Acad Sci. 2000;930:222–232.
16. Bookheimer S. Functional MRI of language: new approaches to understanding the cortical organization of semantic processing. Annu Rev Neurosci. 2002;25:151–188.
17. Catani M, Mesulam M. The arcuate fasciculus and the disconnection theme in language and aphasia: history and current state. Brain. 2008;131(Pt 8):2123–2136.
18. Catani M, ffytche DH. The rises and falls of disconnection syndromes. Brain. 2005;128(10):2224–2239.
19. Leff AP, Schofield TM, Crinion JT, et al. The left-posterior temporal cortex and reading recovery after stroke. Ann Neurol. 2006;59(1):99–107.
20. Geschwind N. Disconnexion syndromes in animals and man. Brain. 1965;88(2):237–294.
21. Saur D, Lange R, Baumgaertner A, et al. Dynamics of language reorganization after stroke. Brain. 2006;129(6):1371–1384.
22. Damasio AR, Damasio H. The anatomic basis of pure alexia. Neurology. 1983;33(12):1573–1583.
23. Benton AL. Disorders of visuoperceptive recognition and their relation to reading and writing. In: Mesulam MM, editor. Principles of Behavioral Neurology. Philadelphia: F.A. Davis; 1985. p. 129–150.
24. Turkeltaub PE, Gareau L, Flowers DL, et al. Development of neural mechanisms for reading. Nat Neurosci. 2003;6(7):767–773.
25. Dejerine J. Sur un cas de cécité verbale avec agraphie, suivi d’autopsie. Mém Soc Biol. 1892;4:61–90.
26. Leff AP, Starrfelt R. Alexia: the neuropsychology of reading disorders. Oxford: Oxford University Press; 2014.
27. Warrington EK, Shallice T. Word-form dyslexia. Brain. 1980;103(1):99–112.
28. Coslett HB, Saffran EM. Mechanisms of reading impairment in alexia without agraphia. Brain. 1989;112(2):327–359.
29. Binder JR, Mohr JP. The topography of callosal reading pathways: a case-control analysis. Brain. 1992;115(6):1807–1826.
30. Behrmann M, Plaut DC. Distributed circuits, not circumscribed centers, mediate visual word recognition. Trends Cogn Sci. 2013;17(5):210–219.
31. Richardson FM, Price CJ. Structural MRI studies of language function. Brain Struct Funct. 2009;213(6):511–523.
32. Déjerine J. Contribution à l'étude anatomo-pathologique et clinique des différentes variétés de cécité verbale. Mém Soc Biol. 1892;4:61–90.

33. Gerstmann J. Syndrome of finger agnosia, disorientation for right and left, agraphia, and acalculia. Arch Neurol Psychiatry. 1940;44:398–408.
34. Roeltgen DP, Heilman KM. Alexia with agraphia. Arch Neurol. 1983;40(9):846–848.
35. Alexander MP, Friedman RB. Lesion localization in alexia. Neuropsychologia. 1984;22(6):747–758.
36. Rapp B, Lipka K. The literate brain: the relationship between spelling and reading. J Cogn Neurosci. 2011;23(5):1180–1197.
37. Caramazza A, Miceli G. The structure of graphemic representations. Cognition. 1990;37(3):243–297.
38. Coltheart M, Patterson K, Marshall JC. Deep Dyslexia. London: Routledge; 1980.
39. Friedman RB. Two types of phonological alexia. Cortex. 1996;32(3):375–387.
40. Nadeau SE, Crosson B. Subcortical aphasia. Brain Lang. 1997;58(3):355–402.
41. Binder JR, Mohr JP. The topography of posterior cortical reading pathways. Brain. 1992;115(6):1807–1826.