What explains the lack of behavioral symptoms in a patient with suspected frontotemporal dementia (FTD)?

Explaining Lack of Behavioral Symptoms in Suspected Frontotemporal Dementia

The lack of behavioral symptoms in a patient with suspected frontotemporal dementia (FTD) can be explained by several factors including genetic variations, atrophy patterns, disease stage, and limitations in assessment tools. 1

Potential Explanations for Lack of Behavioral Symptoms

Genetic Factors

• C9orf72 mutation carriers often present with a slow progressive course and may have atypical neuroimaging findings, potentially masking classic behavioral symptoms 1
• Different genetic mutations (C9orf72, GRN, MAPT) present with varying symptom profiles and progression patterns 2, 3
• GRN mutation carriers may present with psychiatric symptoms that evolve into bvFTD over time rather than classic behavioral symptoms initially 1, 4

Neuroanatomical Considerations

• Atrophy patterns significantly influence symptom presentation - patients with symmetric atrophy may present with less pronounced behavioral changes 5
• Right-lateralized atrophy is associated with specific symptoms like abnormal eating behavior and hallucinations, while left-lateralized atrophy may present with fewer overt behavioral symptoms 5
• Ventral-predominant atrophy correlates with anxiety, euphoria, and disinhibition, while dorsal atrophy patterns may present with fewer behavioral symptoms 5

Disease Stage and Progression

• Behavioral symptoms typically increase in early-intermediate phases and plateau in late stages 2
• Some behavioral symptoms may not appear until later in disease progression, especially in certain genetic variants 2, 3
• Symptoms like apathy may be present but not recognized as a behavioral symptom by caregivers 1

Assessment Limitations

• Standard cognitive screening tools like MMSE often show normal-range scores in early bvFTD, potentially masking behavioral symptoms 1
• The MoCA is more sensitive (78% sensitivity, 98% specificity) for detecting early cognitive changes in FTD 1, 6
• Lack of insight is common in bvFTD patients, leading to underreporting of behavioral symptoms 1

Diagnostic Approach for Suspected FTD with Limited Behavioral Symptoms

Clinical History and Collateral Information

• Obtain detailed collateral history from family members or caregivers, as patients often lack insight into their behavioral changes 1
• Use structured behavioral scales like the Frontal Behavioral Inventory (FBI) or Stereotypy Rating Inventory (SRI) to systematically assess for subtle behavioral changes 1
• The FTD versus PPD Checklist can help standardize assessment of clinical factors that distinguish FTD from psychiatric disorders 1

Neurological Examination

• Perform comprehensive neurological examination focusing on:
  • Parkinsonism signs (bradykinesia, rigidity, parkinsonian gait) which are present in 25-80% of FTD cases 1
  • Oculomotor abnormalities, especially decreased velocity of saccades 1
  • Motor neuron signs and primitive reflexes like the grasp reflex 1

Cognitive Assessment

• Use tests specifically sensitive to frontal lobe dysfunction:
  • Montreal Cognitive Assessment (MoCA) has better classification accuracy (88%) than MMSE for FTD 1, 6
  • Include social cognition tests like the Ekman 60 Faces Test or Mini-SEA 1
  • Frontal Assessment Battery (FAB) for evaluating executive functions 6
  • Tests for motor sequences (Luria's test) and Go/No-Go test for inhibitory control 6

Neuroimaging

• High-resolution 3D-T1 brain MRI with standardized review protocol and visual atrophy rating scales 1
• Consider volumetric analyses if available, as some FTD variants (especially C9orf72) may have atypical or minimal findings on standard imaging 1

Genetic Testing

• Consider genetic testing for C9orf72, GRN, and MAPT mutations, especially if there is:
  • Family history of FTD, ALS, or late-onset psychiatric disorders 1, 4
  • C9orf72 screening is recommended in all cases of suspected bvFTD, even without family history 1
  • C9orf72 screening should be considered in late-onset psychiatric disorders with family history of FTD or ALS 4

Common Pitfalls and Caveats

• Misattribution of symptoms: Restlessness or agitation in FTD may be misinterpreted as anxiety 1
• Reliance on self-report: Self-report psychiatric scales have minimal usefulness in bvFTD due to impaired insight 1
• Normal cognitive screening: Normal MMSE scores are common in early bvFTD and should not rule out the diagnosis 1
• Overlooking psychiatric prodrome: Psychiatric symptoms may precede classic FTD features by several years, especially in C9orf72 carriers 1, 4
• Focusing only on cognitive symptoms: Behavioral symptoms may be subtle or absent initially, especially in certain genetic variants 2, 3

Remember that behavioral symptoms in FTD have different trajectories throughout the disease course, and their absence does not rule out the diagnosis, especially in early stages or in certain genetic variants 2, 3.