Check Your Diagnosis — Patient 23
Albert Yen, M.D.
Alexia without Agraphia;
Cardioembolic CVA involving the left parieto-occipital junction
Patient #23 presented with the acute onset of a right superior quadrantanopsia and alexia without agraphia. These features place the responsible lesion in the left occipital region. Alexia without agraphia classically results from a lesion of the dominant occipital lobe with extension into the splenium of the corpus callosum. Functionally, this lesion disconnects visual input from language comprehension. A patient so affected is able to see (in the unaffected visual field) and understand language, since the primary cortical areas responsible for these activities remain unaffected. The patient is unable to read, however, because visual input is disconnected from language comprehension—visual input is wiped out on the left and visual information from the right occipital lobe cannot reach the language comprehension center because its pathway through the splenium of the corpus callosum is lesioned. In some patients, as in this case, the lesion produces only a dominant field quadrantanopsia. Such a lesion could involve either the inferior optic radiations, in the temporal or occipital lobe, or the inferior occipital pole on the left side. In such cases, one must postulate an additional disconnection between the left visual cortex and the language comprehension center or a primary defect in a "reading center".
This patient, however, demonstrated a feature atypical for the pure syndrome of alexia without agraphia. He reported acalculia, specifically anarithmetria, a function associated with the dominant angular gyrus. There were no other features of the Gerstmann syndrome (no finger agnosia, right-left disorientation, dysgraphia) implying a restricted lesion at the edge of the angular gyrus. The full features of the angular gyrus syndrome (Gerstmann's syndrome and alexia with agraphia) were not present, excluding full involvement of the angular gyrus. Graphaesthesia, stereognosis, and double simultaneous stimulation were intact; and there were no other features suggesting dominant parietal dysfunction. This places the responsible lesion on the left side, at the parieto-occipital junction abutting the angular gyrus and undercutting the inferior optic radiations. This lesion serves the same functional consequence as the lesion seen in classic alexia without agraphia, since the brain region responsible for integrating visual and language information to enable reading is the angular gyrus. A lesion at the edge of the angular gyrus would also disconnect necessary visual information from this center. The consequence is alexia without agraphia accompanied by dysfunction of other features associated with the angular gyrus—namely acalculia (in this case). Other features, typically seen in the classic syndrome of alexia without agraphia, such as color agnosia and achromatopsia were not seen in this patient because the lesion primarily involved parietal cortex, rather than medial occipital cortex. The CT scan confirmed this placement of the lesion. The lesion did not extend into the splenium of the corpus callosum, but such an extension is not necessary in this restricted case, as described above.
The sudden onset of the deficit implies a vascular etiology. Maximal deficit at onset, cortical location, and occurrence in a patient with a prosthetic heart valve imply a cardioembolic source for the stroke. The CT scan showed a wedge-shaped lesion consistent with a recent embolic infarct on the left side at the parieto-occipital junction. This corresponds to an occlusion of a posterior branch of the middle cerebral artery, most likely a branch of the angular artery. The INR (2.2) was low for a patient with a prosthetic heart valve. Recent data from the Netherlands has shown that high intensity anticoagulation with an INR maintained between 3-4 is most effective in preventing cardioembolic stroke in patients with prosthetic heart valves. INRs above 5, however, are associated with an unacceptably high risk of hemorrhage.
The patient was managed with intravenous heparin while his coumadin dose was adjusted to a higher level of anticoagulation. Over the next few days, he noted a gradual improvement in his ability to read. By the time of discharge, he was easily able to read short words (four letters or fewer), but had difficulty with longer words. The visual field deficit disappeared within two days of presentation. His calculation difficulties were improving, but not yet at baseline, at discharge.
Alexia, the acquired inability to read, is a restricted form of aphasia (acquired disturbance of language). Strictly, the term dyslexia is reserved for patients with a developmental difficulty in reading; however, the terms alexia and dyslexia are often used interchangeably to reflect a generic impairment of reading skill, or to denote severity of reading difficulty. One may divide alexias into two major categories: (1) literal dyslexia, or the inability to read individual letters; and (2) verbal dyslexia, or the inability to read words and passages. Global dyslexia refers to the inability to perform either task. Of these, the most commonly encountered is verbal alexia, most commonly caused by the acute confusional state. One may also divide alexias based on location of lesion into posterior, central, and anterior alexias. Posterior alexia corresponds to alexia without agraphia, central alexia to alexia with agraphia, and anterior alexia to a reading dysfunction characterized by impaired ability to comprehend syntactic structures. Each will be discussed in more detail below.
Readers may deduce the meaning of printed words by three mechanisms. In whole-word reading, words are recognized as units rather than strings of letters. This requires that the words in question be in the reader's vocabulary. In phonemic analysis, the reader separates words into letters, translates letters into the sounds they represent, and identifies the words by sound recognition. In word recognition by context, the reader uses the context in which a word appears to deduce its meaning. There are two routes, using the mechanisms above, by which we read. Readers may use a direct (lexical) route, whereby they access the mental representations of words and their meanings directly, based on the visual form of the words. Readers may also use an indirect (phonologic) route, by converting graphemes to phonologic equivalents and accessing meaning via these phonologic representations. Two forms of word-reading impairment have been well-described. In surface dyslexia, the direct (lexical) route, which works by whole-word reading, is impaired. In this condition, patients cannot read words as a whole, but must rely on the indirect (phonologic) route to decode words by sounding them out letter by letter. Such individuals cannot read irregularly spelled words but can read aloud phonologically legitimate non-words. In deep dyslexia, the indirect (phonologic) route is impaired and patients must rely on the direct (whole-word) route. Such patients can recognize and read aloud only familiar, concrete words. A third form is equivalent to the pure form of alexia without agraphia, whereby the patient can only make sense of words letter-by-letter.
In 1891 and 1892 Dejerine published two cases primarily characterized by the acquired inability to read, the first associated with an impairment of writing ability and the second with preserved writing. In both cases, the responsible pathology had a different anatomical location. Subsequently, numerous cases have been described with pathology located in the occipital lobe (posterior alexia), angular gyrus (central alexia), and frontal lobe (anterior alexia).
The pure syndrome of alexia without agraphia is best viewed as a "linguistic blindfold". Patients so afflicted are able to write, but cannot read their own written words. The primary deficit is an inability to comprehend written material. Patients readily understand words spelled aloud or words written on the palm. Some patients demonstrate a literal alexia, unable to recognize any written letters. Most can recognize some individual letters and, with practice, can learn to read most letters out loud and thereby recognize words auditorily. Other aspects of language, such a fluency, auditory comprehension, writing, and repetition are normal. A mild anomia is common but not invariably present. A complete right hemianopsia is present in most cases; but exceptions, some with partial field defects, are observed. Sensory loss and motor dysfunction are not observed. Deficits in color vision and color naming may also be seen. Impairment in naming and understanding color names (color agnosia) in the presence of intact color vision is common. Acquired impairment of color vision (achromatopsia) is uncommon, but has been described.
The responsible lesion is most commonly a stoke in the territory of the left posterior cerebral artery, with resulting infarction of the medial occipital lobe, splenium of the corpus callosum, and often the medial temporal lobe. Cases have also been associated with hematoma, vascular malformation, multiple sclerosis, tumor, abscess, migraine, carbon monoxide poisoning, and transtentortial herniation. Such a lesion, by infarcting the left visual cortex, will cause a right homonymous hemianopsia (cutting off the flow of information from the left occipital cortex to the left angular gyrus), and, by extending into the splenium, disconnect the unaffected right occipital lobe from the left angular gyrus. Words can be seen in the left hemifield but not comprehended, since no visual information can enter the left angular gyrus (where visual and language information are combined). Achromatopsia results from involvement of the dominant inferior occipital lobe, where color vision is largely processed. When the right hemianopia is only partial, the lesion must be so placed as to impede the transfer of information from the intact left visual field to the left angular gyrus. More recently, Benito-Leon and colleagues suggested that alexia without agraphia without a full visual field deficit may result from damage to a word recognition area located in visual association cortex rather than a disconnection syndrome. In normal volunteers, visual presentation of words activates regions in the dominant, medial visual association cortex by PET study. These areas are not activated by presentation of nonsense strings of letters. This may explain why some patients demonstrating alexia without agraphia do not have involvement of the splenium, and why reading of single letters is spared.
In central alexia, patients demonstrate an inability to read or write (alexia with agraphia), prompting the description "acquired illiteracy". Patients so afflicted do not recognize words spelled aloud or written in the palm (global dyslexia), though they retain the ability to copy written language slavishly and without comprehension. Visual field deficits are uncommon and vary from full to none. Aphasia is ususally present—most commonly anomic aphasia, but rarely Wernicke's or transcortical sensory aphasia may dominate the picture. The responsible lesion is in the dominant inferior parietal lobule involving the angular gyrus, but may extend anteriorly or posteriorly. The most common cause is middle cerebral artery occlusion, accounting for the variability in findings.
Another form of alexia commonly accompanies Broca's aphasia, representing an extension of the basic language defect of this aphasia to written material. The most striking feature of this alexia is an impaired ability to understand function words, such as conjunctions, and word endings. Patients with anterior alexia understand single, semantically significant words but cannot handle sequences of these words, as is commonly encountered in written material. The location of the responsible pathology is the same as for Broca's aphasia.
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