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EinoSolje
JohannaKrüger

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.