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Frontotemporal Lobar Degeneration
Essentials
- Frontotemporal lobar degeneration (FTLD) is a group of progressive memory disorders with atrophy in the frontotemporal lobes of the brain.
- Frontotemporal dementia
- Primary progressive aphasia
- Progressive nonfluent aphasia
- Semantic dementia
- Logopenic progressive aphasia
- FTLD plus syndromes
- Progressive supranuclear palsy (PSP)
- Corticobasal degeneration
- About 30% of all progressive memory disorders belong to the FTLD group.
- In about 50% of patients, excluding those with FTLD plus syndromes, there is a positive family history.
- The most common genetic aetiology associated with frontotemporal lobar degeneration is a non-coding repeat expansion of the C9orf72 (chromosome 9 open-reading frame 72) gene.
- Study of the C9orf72 mutation may be beneficial for the diagnosis of these diseases.
- FTLD patients of non-Finnish origin commonly have mutations in GRN and MAPT genes, as well.
- Genetic testing is done in specialized care.
- As frontotemporal lobar degeneration may have several underlying neuropathological subtypes, there are no specific biomarkers available for the disease.
- CSF biomarker (tau, p-tau and amyloid β) tests used for the diagnosis of Alzheimer's disease do not reliably distinguish between frontotemporal lobar degeneration and Alzheimer's disease.
- Normal findings in conventional cognitive screening tests (CERAD and MMSE) do not exclude diseases of the FTLD group.
- The disease should primarily be diagnosed and treatment started by a neurologist, geriatrician or other physician with expertise in memory disorders.
Frontotemporal dementia
- Accounts for about half of all cases of FTLD.
- Disease onset usually occurs between the ages of 45 and 65.
- Hereditary disease, in particular, may begin as early as at the age of 30.
- FTLD with onset after the age of 70 is not rare, either.
- The average duration of the disease is 8 years but there is substantial variation (2-20 years).
- Typical clinical features:
- Changes in behaviour and personality (disinhibition, impulsiveness, tactlessness, impaired judgement)
- Problems with executive functions (planning, ability to concentrate, attention)
- Early impairment of social skills
- Apathy and introversion
- Decline in reasoning ability and problem solving
- Impaired speech production
- Diminished insight into the disease
- Hyperorality, i.e. changes in eating/drinking habits (binge eating, particularly craving for sweet foods, increased consumption of alcohol or tobacco)
- Subjective memory symptoms
- Extrapyramidal symptoms and findings (rigidity, hypomimia, hypo- and bradykinesia)
- Psychosis-like symptoms
- Atrophy in the frontal and/or temporal lobes can be detected by magnetic resonance imaging (MRI) of the brain, and functional imaging techniques (PET, SPECT) can detect corresponding hypoperfusion and hypometabolism.
- In early and moderately severe disease, imaging may give normal findings.
- Alzheimer's drugs are contraindicated, as they often aggravate the clinical picture.
- Symptomatic treatment
- Usual treatment of psychotic and affective symptoms
- Antipsychotics, in particular, should be used at the lowest possible doses, as the patients are sensitive to extrapyramidal adverse effects.
- Benzodiazepines should mostly be avoided since the disease pathology involves damage to the gamma-aminobutyric acid system.
- Regular assessment of driving ability and legal competence
- Ensuring a well-balanced diet and treatment of any deficiencies
- The disease is often complicated by other problems associated with general care.
Progressive nonfluent aphasia
- Typical clinical features:
- Insidious onset and gradual progression
- Laboured, fragmental speech
- Dyslalia and paraphasia (apraxia of speech)
- Impaired comprehension of grammatically complicated sentences
- Comprehension of single words preserved
- Face and object recognition preserved
- MRI of the brain shows atrophy usually in the left frontal lobe and the anterior areas of the temporal lobe.
Semantic dementia
- Typical clinical features:
- Insidious onset and gradual progression
- Language output in conversation is fluent but the speech does not convey meaning.
- Evident difficulty naming things
- Difficulty understanding words
- Impaired recognition of faces and objects
- Difficulty reading and writing
- Repetition of words and sentences is effortless but understanding of the content is gradually lost.
- Speech is well articulated and grammatically normal.
- Behavioural changes
- Lack of insight into symptoms
- MRI of the brain shows atrophy in the area of the middle and inferior temporal gyri.
Logopenic progressive aphasia
- Typical clinical features:
- Finding words in speech and naming is impaired.
- Repetition of sentences or phrases is impaired.
- Dyslalia in spontaneous speech and naming
- Understanding of individual words and recognition of faces and objects are preserved.
- Motorically, speech is effortless.
- No significant grammatical mistakes
- Memory symptoms during the first few years
Progressive supranuclear palsy
- First symptoms usually at the age of about 50-60 years
- Average duration of disease approx. 5-8 years
- Typical clinical features:
- A tendency to fall backward
- Vertical disturbance of eye movements (difficulty aiming the eyes downward, in particular)
- Staring gaze, hypomimia
- Symmetric rigidity of the neck and trunk, in particular
- Other extrapyramidal findings and symptoms (rigidity, hypo- and bradykinesia)
- Later often problems with swallowing, slurred speech
- Cognitive symptoms resembling frontotemporal dementia
- Depression, anxiety, irritability
- Response to Parkinson's drugs is often poor but some patients may benefit from levodopa.
Corticobasal degeneration
- First symptoms usually at the age of about 60 years
- Typical clinical features:
- A tendency to fall backward
- Extrapyramidal symptoms starting unilaterally (hypo- and bradykinesia, rigidity)
- Gradually developing forced dystonic posture and myoclonia of one upper limb
- "Alien limb" syndrome (the patient may feel that the limb is not a part of his/her body and in a way lives its own life with involuntary movements)
- Some patients have signs of upper motor neuron injury, such as spasticity, brisk tendon reflexes and positive Babinski sign
- Unilateral cortical dysaesthesia
- Depression, apathy, lack of inhibition
- Frontal lobe dementia type cognitive symptoms and findings
- Response to Parkinson's drugs is often poor but some patients may benefit from levodopa.
- Symptomatic treatment with clonazepam can be tried cautiously for severe myoclonia.