Alexia

Etiology

Alexia ranges on a spectrum from very mild reading deficit to a complete inability to comprehend written language often associated with agraphia, the inability to write. The most common cause of alexia is a stroke (embolic or ischemic cerebral vascular accident) affecting the dominant cerebral hemisphere, although it may be caused by other etiologies resulting in a disruption to that area such as lesions, injury, or trauma.[7] The specific area of the brain affected results in three distinct types of alexia: frontal or anterior alexia, central or parietal-temporal alexia, and posterior or occipital alexia. Each type is characterized by specific deficits in reading comprehension with or without other neurocognitive deficits.[8]

Epidemiology

Isolated alexia without agraphia is uncommon, and statistics are limited. However, it is often associated with other types of strokes and neurological deficits caused by cerebral vascular accidents. Strokes cause a significant amount of morbidity and mortality worldwide in both women and men. Statistics from 2017 show an incidence rate of stroke at 140.3 to 161.8 per 100,000 in 2017.[9][10]

Pathophysiology

There are varying degrees of comprehension deficit resulting in different types of alexia, including occipital or posterior alexia, central or parietal-temporal alexia, and frontal or anterior alexia.[1] The neuroanatomical area that controls visual perception and interpretation is known as the visual word form area (VWFA) located in the occipitotemporal gyrus.[2] Most of the language processing occurs around the angular gyrus of the left hemisphere, the dominant hemisphere for most of the population. Damage to these areas can result in multiple language-related deficits such as Broca's aphasia, Wernicke's aphasia, global aphasia, alexia, and others. In each form of alexia, a different area of the brain is found to be damaged. There are three major classifications of alexia with different alexia syndromes associated with each.

The first presentation is known as alexia without agraphia, pure alexia, posterior alexia, or occipital alexia and is associated with damage to the occipital region. The visual word form area is affected, and visual input cannot be relayed to the language comprehension areas of the brain. The communicating area between the auditory centers and the language centers is maintained, resulting in the retained ability to interpret words spelled out to or by the individual.[8]

• Associated with infarction to the left posterior cerebral artery and or hemorrhage in the occipital territory, usually affecting the splenium of the corpus callosum, which helps the visual cortex communicate with the language centers of the brain.[2] 
• Often associated with a contralesional visual field defect resulting in hemianopia (loss of sight to half the visual field), most commonly right visual field defect.[7] 
• Individuals lose the ability to comprehend written language but maintain the ability to spell and write.[1]
• The area of auditory input is unaffected, and the individual is able to interpret words spelled out to them or by them.[1] 

The second presentation, known as central or parietal-temporal alexia, is associated with damage to the angular gyrus. Central alexia involves damage to the pathways connecting the visual word form area and the auditory area to the language centers of the brain, resulting in word blindness as well as the inability to spell out or recognize spelled out words.[8]  

• Associated with infarction to the left posterior cerebral artery, middle cerebral artery, and or hemorrhage to the angular gyrus.[2] 
• Associated with aphasia and agraphia. The individual will have difficulty with speech production and comprehension.
• Associated with right visual field defect and often times contralateral hemisensory neglect or loss. 
• Complete loss of interpretation of written speech, inability to distinguish individual letters, inability to interpret words spelled out to them, or spell out words themselves.[8] 

The third presentation, known as frontal or anterior alexia, is associated with an anterior lesion to the left hemisphere. The visual word form area is spared, resulting in the ability to interpret written language through verbal working memory. The individual is able to recover word identity by recognition of common or content words. 

• Associated with infarction, hemorrhage, injury, or trauma to the anterior part of the left hemisphere. 
• Decreased reading comprehension with recognition of content words and short words but complete or partial letter blindness.[1] 
• Associated with agraphia as well as the inability to comprehend spelled out words and inability to spell words out themselves.[8] 
• Associated with non-fluent aphasia. 
• Associated with right visual field defect and often times contralateral hemisensory neglect or loss.[8]

History and Physical

Alexia without agraphia, pure alexia, posterior alexia, or occipital alexia is associated with damage to the occipital region.[8] 

• Individuals lose the ability to comprehend written language but maintain the ability to spell and write. In this scenario, the individual will be able to write out a full sentence but then is unable to read back what was just written.[1]
• Individuals may recognize the letters and be able to spell out the words and derive meaning from what is read by audition.[8] The individual does not rely on the material read but rather on the sounds produced by spelling out or phonographically sounding out the individual letters and can, therefore, comprehend what is being heard, not read. If the individual were to read silently, there would be no comprehension.[1]
• Often associated with hemianopia. Individuals will have a right-sided visual field deficit. 

Central or parietal-temporal alexia is associated with damage to the angular gyrus. 

• Complete letter and word blindness the individual is unable to read or recognize words or letters. Therefore they are unable to create a phonographic interpretation of what is written, unlike what is seen with occipital alexia.  
• Associated with the inability to interpret words spelled out to them as well as the inability to spell out words themselves. 
• Associated with agraphia, the inability to write.
• Associated with aphasia of varying forms, fluent vs. non-fluent.
• Often associated with hemiparesis and visual field defect. 

Frontal or anterior alexia is associated with an anterior lesion to the left hemisphere. 

• Individuals will be able to guess content words, as well as short words, but have limited comprehension of the reading material.
• Inability to recognize individual letters, loss of letter interpretation when words are spelled out to them, and inability to spell out words themselves. 
• Associated with non-fluent aphasia.
• Associated with right visual field defect and often contralateral hemisensory neglect or loss.[8]

Evaluation

Evaluation of a patient with alexia includes a thorough physical examination to assess for reading fluency as well as comprehension. A baseline reading level prior to the insulting injury would be beneficial to the evaluation of the patient. Patients should be asked to read short stories and evaluated on comprehension of the material and the speed at which the material was read. Patients should also be evaluated on their ability to spell out words, comprehend spelled words, and writing. A comprehensive neurological examination should be completed to assess for other neurocognitive disfunction. Neuroimaging with a computed tomography (CT) scan or magnetic resonance imaging (MRI) may be done to help localize the affected area, severity, and acuity of the condition. A stat head CT scan should be done on anyone presenting with new-onset alexia to assess for acute cerebral vascular accidents.[1][2][6] MRI brain has a higher sensitivity than a head CT and must be considered if the head CT is nondiagnostic.

Treatment / Management

Treatment and management of alexia are focused on rehabilitation strategies to improve reading. The treatment modality for alexia depends on the neuroanatomical area affected, as described above. For individuals with intact letter recognition, a letter-by-letter approach to reading is used in which each letter is sounded out individually. For patients with intact writing skills, a kinesthetic approach is used. In this approach, the patient will trace or outline the letters and sound them out by the tactile input provided from writing the letter. These tactics can be used regularly to increase reading speed over time. Although this may improve symptoms, a definite cure for the disorder has not been found.[11]

Differential Diagnosis

Alexia is the inability to comprehend written language due to focal brain injury in the temporal lobe. It is important to distinguish alexia from other disease processes that impair reading. These may include visual impairment, eye trauma or injury, cataracts or blindness, other neurocognitive disorders such as global aphasia, dementia, intoxication, mutism, and psychiatric conditions such as catatonia, depression, or schizophrenia.[12][13][14]

Prognosis

The prognosis for patients suffering from alexia is variable and highly dependant on multiple variables. The type of alexia, cause of injury, and amount of rehabilitation done after the insulting injury play a critical role in determining prognosis. Although individuals may improve their reading comprehension, complete resolution is rare.[11]

Complications

Complications of alexia encompass a spectrum of reading disabilities that range from permanent loss of comprehension to mild reading impairment. Alexia almost always accompanies other neurocognitive deficits associated with the inciting insult. These conditions include but are not limited to complete aphasia, hemineglect, visual field deficits, and death.[6][8]