What is aphasia?Aphasia is an acquired disorder caused by brain damage which affects a person’s ability to communicate. The principal signs of aphasia are impairments in the ability to express oneself when speaking, trouble understanding speech, and difficulty with reading and writing. Aphasia is most often the result of stroke or head injury but can also occur in other neurological disorders, such as in certain forms of dementia. The effects of aphasia differ from person to person. Strategies to communicate non-verbally (without words) may be helpful to the person with aphasia.
Primary progressive aphasia(PPA) is a rare neurological syndrome in which language capabilities become slowly and progressively impaired. People with primary progressive aphasia are fighting against a condition in which they will continue to lose their ability to speak, read, write, and/or understand what they hear without effective treatment. Usually, people with aphasia that results from stroke or head injury will experience improvement over time, often aided by speech therapy. This is not the case for people with primary progressive aphasia. Most people with primary progressive aphasia maintain ability to take care of themselves, pursue hobbies, and, in some instances, remain employed in the early phases of this disorder. Primary progressive aphasia(PPA) is uncommon, with Alzheimer disease pathology underlying in one-third of the patients, and pathology characteristic of frontotemporal dementia in two-thirds of patients[1-2].
Improvement in PPA following treatment with perispinal etanercept at the INR has been reported[2].
Basic science, genetic, epidemiologic, and clinical evidence suggests that excess tumor necrosis factor-alpha (TNF) may play a central role in the pathogenesis of Alzheimer’s disease[3-23]. Additionally, excess TNF has been documented in the cerebrospinal fluid of patients with frontotemporal dementia[24]. Excess TNF may, therefore, represent a therapeutic target in PPA. Etanercept, a recombinant dimeric anti-TNF fusion protein, binds to TNF and blocks its interaction with cell surface TNF receptors, thereby reducing the biologic effect of excess TNF. Emerging evidence suggests that perispinal administration of etanercept may have therapeutic efficacy in Alzheimer’s disease[25-32]. This evidence, in combination, supports a rationale for a trial of perispinal etanercept for PPA.
Rapid improvement in verbal abilities, beginning within twenty minutes of perispinal etanercept, in a patient with severe PPA, has been reported[2]. With repeated weekly dosing, sustained improvement at one month was documented, with a more than ten point improvement in the patient’s abilities to perform activities of daily living, as measured by a standarized instrument, the Alzheimer’s Disease Cooperative Study-Activities of Daily Living inventory[2]. Rapid clinical improvement in PPA following perispinal etanercept administration may be related to TNF’s role as a gliotransmitter and modulator of synaptic communication in the brain. These results may provide insight into the basic pathophysiologic mechanisms underlying PPA and related forms of dementia, and suggest the existence of novel, rapidly reversible, TNF-mediated pathophysiologic mechanisms in both PPA and Alzheimer’s disease[2, 30-32].
Evaluation and treatment of selected patients with PPA is available at the INR after physician consultation.
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