Frontotemporal dementia with Parkinsonism-17 (FTDP-17) is an autosomal dominant neurodegenerative disease that affects behavior , speech and movement. Symptoms of this disease, as a rule, become noticeable after 40 years. Most patients live 5 to 10 years after the onset of symptoms, although cases with longer survival have been described [1] .
Personality and behavioral changes are often the first signs of FTDP-17. These changes include loss of inhibition, inappropriate emotional reactions, anxiety, neglect of personal hygiene, and a general loss of interest in activities and events. The disease also leads to a deterioration in cognitive functions ( dementia ), including problems with judgment, planning, and concentration. Some patients with FTDP-17 develop psychiatric symptoms, including obsessive-compulsive behavior, delirium, and hallucinations . This makes it difficult for patients to interact with other people in a socially appropriate manner. They increasingly require help with personal hygiene and other aspects of everyday life.
Many people with FTDP-17 experience speech and language problems. They may have problems finding words, confuse one word with another (semantic paraphases), repeat words spoken by others ( echolalia ). Difficulties with speech and language increase over time, which may ultimately lead to a loss of communication ability.
The FTDP-17 is also characterized by traffic problems. Many patients exhibit some features of parkinsonism, including tremor, muscle rigidity, and unusually slow movement ( bradykinesia ). As the disease progresses, the most affected individuals become unable to walk. Some people with FTDP-17 experience limitations in the vertical movement of the eyes (vertical gaze paralysis), and some patients experience rapid abnormal movements of both eyes ( saccades ).
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Epidemiology
Worldwide, the prevalence of FTDP-17 is unknown. In the Netherlands, where the prevalence of this disease has been studied, it affects approximately 1 in 1,000,000 people. However, most likely, there is a hypodiagnosis and the actual picture may differ to a greater extent compared with the number of recorded cases.
FTDP-17 is likely to cause a certain percentage of all cases of frontotemporal dementia.
Genetics
The disease is caused by mutations in the MAPT gene. This gene is localized on chromosome 17 .
The MAPT gene provides instructions for a protein called tau. This protein is found in nerve tissue, including brain neurons. He is involved in the assembly and stabilization of microtubules - rigid hollow fibers that make up the structural basis of the cell (cytoskeleton). Microtubules help cells maintain their shape, contribute to the process of mitosis, and are essential for the transport of substances in cells.
Mutations in the MAPT gene disrupt the normal structure and function of tau. A defective protein collects in clots within abnormal neurons and other brain cells. However, it is not clear what effect these clots have on cell function and survival. FTDP-17 is characterized by gradual cell death in the frontal and temporal lobes of the brain. The frontal lobes are involved in reasoning, planning and problem solving, while the temporal lobes are involved in the processes of hearing, speech, memory, and emotion. Loss of cells in these areas of the brain leads to personality changes, speech difficulties and other features of FTDP-17.
FTDP-17 is one of several related diseases known as tauopathies, which are characterized by abnormal accumulation of tau in the brain.
More on the MAPT gene.
This disease is inherited in an autosomal dominant manner, which means that mutations in one allele are enough to cause the disorder.
Clinical picture
The main manifestations of the disease are associated with impaired functions of the frontotemporal structures of the brain. The following symptoms are distinguished depending on the localization of the process:
- decreased interest in the environment
- apathy or, conversely, aggressiveness
- disinhibition
- decline in criticism of their behavior
- change in your behavior
- eating behavior change
- violation of expressive speech (in the form of its slowdown)
- loss of verbs ( dynamic aphasia )
- Broca's motor aphasia
The following manifestations of the disease are also possible:
- amnestic dysphasia
- semantic dysphasia
During a neurological examination, signs of oral automatism reflexes, a grasping reflex , revitalization of tendon reflexes, characteristic of lesions of the frontal lobes, are revealed, later disturbances in standing and walking, hypokinesia and falling. [2]
Diagnostics
The diagnosis is made on the basis of clinical data, a family history, the presence of atrophy of the frontal or temporal lobe with CT or MRI. The final diagnosis is made with a brain biopsy or autopsy . [2]
Treatment
Pathogenetically substantiated therapy does not exist. Symptomatic therapy involves the correction of patient behavior, the elimination of psychotic disorders, the normalization of nutrition, sleep, etc. [2]
Notes
- β Foster NL et al. Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference // Annals of neurology. - 1997. - T. 41. - No. 6. - S. 706-715
- β 1 2 3 Parfenov V.A. Nervous diseases. - 2014.