Skip to content
How It Works
Explore
Ask a Question Resources Pricing
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Ask a Question
PubMed This is a summary of 21 peer-reviewed journal articles Updated
Neurology

The Road to a Diagnosis: Tests and Mimics

At a Glance

FTD-ALS is diagnosed from the overall pattern of behavior, language, cognitive, and motor symptoms rather than one test. Neurological examination, ECAS, EMG, MRI, blood or spinal-fluid NfL, genetic testing, and mimic evaluation help clarify the diagnosis.

Diagnosing the FTD-ALS spectrum is a complex process because it involves two different systems: the parts of the brain that control behavior and language, and the nerves that control movement. Because there is no single “yes or no” test, doctors use a combination of clinical exams, electrical testing, and advanced imaging to build a complete picture [1][2].

The Clinical “Gold Standard”

The diagnosis is primarily clinical, meaning it is based on the patterns of symptoms a neurologist observes. Modern guidelines use the term ALS Frontotemporal Spectrum Disorder (ALS-FTSD) to describe the wide variety of ways these symptoms can overlap [3][4].

  • The Exam: A neurologist looks for “upper motor neuron” signs (like stiff muscles or overactive reflexes) and “lower motor neuron” signs (like muscle wasting or twitching) [1][5].
  • Cognitive Screening: Because traditional memory tests often miss FTD symptoms, specialized tools like the ECAS (Edinburgh Cognitive and Behavioural ALS Screen) are used to specifically check for executive and language changes common in this spectrum [6][7].

Key Diagnostic Tests

While the exam is central, several tests provide the evidence needed to support the diagnosis and rule out other possibilities. Not every patient needs every test on this list.

  • EMG and Nerve Conduction Studies: These “electrical” tests check the health of your muscles and the nerves that control them. In FTD-ALS, the EMG (electromyography) looks for signs of active denervation—evidence that muscles are losing their nerve supply—even in limbs that still feel strong [2][8].
  • Brain MRI: In this spectrum, an MRI may show atrophy (shrinking) in specific regions, particularly the motor cortex (which controls movement) and the anterior insula (which helps process emotions and social cues). However, MRI findings are variable, may be completely normal early on, and are mainly supportive or useful for excluding mimics [9][10].
  • Neurofilament Light (NfL): This is an emerging biomarker measured in blood or spinal fluid. NfL is a protein that leaks out when nerve cells are damaged. While high levels are very common in ALS, NfL is a nonspecific marker of neuronal injury. It cannot by itself confirm ALS-FTSD or reliably distinguish it from every psychiatric or other neurological condition [11][12].

Ruling Out “Look-Alikes”

Because early FTD-ALS can look like other conditions, doctors must carefully exclude other causes. Sensory symptoms, marked pain, sphincter symptoms, or a rapidly fluctuating course may point toward a mimic.

  • Psychiatric Disorders: Early behavioral changes can be mistaken for late-onset depression or personality disorders. High NfL levels can sometimes help distinguish a physical brain disease from a primary psychiatric condition [13][14].
  • Structural Mimics: Problems in the neck (like cervical myelopathy) can cause arm weakness and reflex changes that look like ALS. Spinal MRIs are often performed to ensure a physical blockage isn’t the cause [15][16].
  • Other Dementias: Alzheimer disease can initially present with language, visuospatial, or executive problems, and FTD can also involve memory difficulties. History, examination, imaging, and validated fluid or molecular biomarkers are integrated rather than relying on a simple memory-versus-behavior distinction [17].

The Genetic Connection

Genetic testing is increasingly recommended or offered in ALS and selected FTD presentations, especially for the C9orf72 repeat expansion [18][19]. Identifying a genetic cause can help with family planning and may open doors to observational research programs like ALLFTD (though participation in ALLFTD does not guarantee access to a future trial) [20].

Because these results affect the entire family, meeting with a genetic counselor before and after testing is strongly advisable to navigate informed-consent, privacy/insurance, psychosocial, family-planning, and variant-interpretation considerations [6].

A Typical Testing Checklist

A thorough diagnostic evaluation for FTD-ALS often includes:

  1. Comprehensive Neurological Exam: Checking for both upper and lower motor neuron signs [1].
  2. ALS-Specific Cognitive Testing: Using tools like the ECAS rather than just a standard memory test [6].
  3. EMG/Nerve Conduction Study: Testing multiple body regions (arms, legs, and sometimes the tongue or paraspinal muscles) [2].
  4. Neuroimaging: High-resolution MRI of the brain and, often, the cervical spine [9][15].
  5. Genetic Consultation: Discussion and testing for C9orf72 and other relevant genes [20].
  6. Blood Work: To rule out mimics like vitamin deficiencies, thyroid issues, or inflammatory conditions [21].
  7. Multidisciplinary Review: Ideally, the results are reviewed by a team at a specialized FTD or ALS center [6].

Common questions in this guide

How is the FTD-ALS spectrum diagnosed?
There is no single test that confirms FTD-ALS. Doctors combine the pattern of behavior, language, thinking, and movement changes with a neurological examination, cognitive screening, EMG, imaging, and other tests that help rule out similar conditions.
What can an EMG show in FTD-ALS?
An EMG can detect active denervation, which means muscles are losing some of their nerve supply. It may find lower motor neuron changes in parts of the body that still seem strong, so doctors may test several regions along with nerve conduction studies.
Can an MRI confirm FTD-ALS?
An MRI cannot confirm FTD-ALS by itself. It may show shrinkage in areas such as the motor cortex or anterior insula, but scans can be normal early; MRI is also useful for looking for structural problems that can mimic the condition.
What does a high NfL level mean?
A high neurofilament light, or NfL, level suggests that nerve cells are being injured, but it is not specific to FTD-ALS. NfL is common in ALS and other neurological conditions, so it cannot establish the diagnosis or distinguish every possible mimic on its own.
What conditions can look like FTD-ALS?
Behavioral or language changes may occur with psychiatric disorders or other dementias, including Alzheimer disease. Neck spinal cord problems, vitamin or thyroid disorders, inflammatory conditions, and other neurological diseases can also cause some ALS-like findings, so doctors use the history, examination, imaging, and laboratory tests together.
Should I consider C9orf72 genetic testing?
Genetic testing may be offered or recommended in ALS and selected frontotemporal dementia presentations, especially when C9orf72 is a concern. A genetic counselor can explain possible results, privacy and family implications, and how testing may affect family planning before and after the test.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does my loved one's presentation fit the clinical criteria for ALS-FTSD, and which 'category' of the spectrum are they currently in?
  2. 2.What specific 'lower motor neuron' signs did the EMG find, and do they extend beyond the areas where we have already noticed weakness?
  3. 3.Can you show us the MRI and explain how it helped exclude other potential conditions?
  4. 4.How does the NfL level in the blood or CSF help clarify the diagnosis versus other possible conditions?
  5. 5.Which 'look-alike' conditions were ruled out, and what tests were used to do so?
  6. 6.Is genetic testing for C9orf72 and other spectrum genes recommended for us, and can we meet with a genetic counselor first?
  7. 7.Are we eligible for any observational research programs like ALLFTD?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (21)
  1. 1

    Amyotrophic lateral sclerosis; clinical features, differential diagnosis and pathology.

    Van Es MA

    International review of neurobiology 2024; (176()):1-47 doi:10.1016/bs.irn.2024.04.011.

    PMID: 38802173
  2. 2

    Amyotrophic lateral sclerosis or not: Keys for the diagnosis.

    Lenglet T, Camdessanché JP

    Revue neurologique 2017; (173(5)):280-287 doi:10.1016/j.neurol.2017.04.003.

    PMID: 28461025
  3. 3

    Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria.

    Strong MJ, Abrahams S, Goldstein LH, et al.

    Amyotrophic lateral sclerosis & frontotemporal degeneration 2017; (18(3-4)):153-174 doi:10.1080/21678421.2016.1267768.

    PMID: 28054827
  4. 4

    Cognitive and Behavioral Manifestations in ALS: Beyond Motor System Involvement.

    Rusina R, Vandenberghe R, Bruffaerts R

    Diagnostics (Basel, Switzerland) 2021; (11(4)) doi:10.3390/diagnostics11040624.

    PMID: 33808458
  5. 5

    Primary progressive aphasia and motor neuron disease: A review.

    Aiello EN, Feroldi S, De Luca G, et al.

    Frontiers in aging neuroscience 2022; (14()):1003792 doi:10.3389/fnagi.2022.1003792.

    PMID: 36158556
  6. 6

    Pan-Asian consortium for treatment and research in ALS (PACTALS) guidelines for management of amyotrophic lateral sclerosis.

    Vucic S, Shahrizaila N, Kano O, et al.

    The Lancet regional health. Western Pacific 2025; (62()):101684 doi:10.1016/j.lanwpc.2025.101684.

    PMID: 41018945
  7. 7

    What is the extent of reliability and validity evidence for screening tools for cognitive and behavioral change in people with ALS? A systematic review.

    Didcote L, Vitoratou S, Al-Chalabi A, Goldstein LH

    Amyotrophic lateral sclerosis & frontotemporal degeneration 2024; (25(5-6)):437-451 doi:10.1080/21678421.2024.2314063.

    PMID: 38415696
  8. 8

    Awaji criteria for the diagnosis of amyotrophic lateral sclerosis in Hanoi, Vietnam.

    Van Nguyen T, Tran TA, Vu HT

    Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2022; (43(1)):393-398 doi:10.1007/s10072-021-05333-9.

    PMID: 34023955
  9. 9

    Tackling clinical heterogeneity across the amyotrophic lateral sclerosis-frontotemporal dementia spectrum using a transdiagnostic approach.

    Ahmed RM, Bocchetta M, Todd EG, et al.

    Brain communications 2021; (3(4)):fcab257 doi:10.1093/braincomms/fcab257.

    PMID: 34805999
  10. 10

    COG-01 Phenotypic variation in 
ALS-FTD and effect on survival.

    Ahmed RM, Devenney EM, Strikwerda-Brown C, et al.

    Amyotrophic lateral sclerosis & frontotemporal degeneration 2019; (20(sup1)):301-308 doi:10.1080/21678421.2019.1647000.

    PMID: 31702468
  11. 11

    The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis: A systematic review and meta-analysis.

    Forgrave LM, Ma M, Best JR, DeMarco ML

    Alzheimer's & dementia (Amsterdam, Netherlands) 2019; (11()):730-743 doi:10.1016/j.dadm.2019.08.009.

    PMID: 31909174
  12. 12

    Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS.

    Halbgebauer S, Steinacker P, Verde F, et al.

    Journal of neurology, neurosurgery, and psychiatry 2022; (93(1)):68-74 doi:10.1136/jnnp-2021-327129.

    PMID: 34417339
  13. 13

    Neurofilament Light Chain and Differentiation of Behavioral Variant Frontotemporal Dementia From Psychiatric Disorders: A Systematic Review.

    Davydow DS, Brasfield M, Morrow CB, et al.

    JAMA psychiatry 2026; (83(1)):85-98 doi:10.1001/jamapsychiatry.2025.2429.

    PMID: 40928798
  14. 14

    Neurofilaments can differentiate ALS subgroups and ALS from common diagnostic mimics.

    Behzadi A, Pujol-Calderón F, Tjust AE, et al.

    Scientific reports 2021; (11(1)):22128 doi:10.1038/s41598-021-01499-6.

    PMID: 34764380
  15. 15

    Predictors of amyotrophic lateral sclerosis mimic syndrome.

    Quarracino C, Segamarchi MC, Rodríguez GE

    Acta neurologica Belgica 2019; (119(2)):253-256 doi:10.1007/s13760-019-01135-1.

    PMID: 30972662
  16. 16

    Amyotrophic lateral sclerosis and degenerative cervical myelopathy: phenotype-based diagnostic pitfalls, investigative mismatch, and practical clinical reasoning.

    Chen D, Shen T, Ren H, Qiu P

    Frontiers in neurology 2026; (17()):1901811 doi:10.3389/fneur.2026.1901811.

    PMID: 42625715
  17. 17

    Cerebrospinal Fluid and Blood Neurofilament Light Chain Protein in Prion Disease and Other Rapidly Progressive Dementias: Current State of the Art.

    Abu-Rumeileh S, Parchi P

    Frontiers in neuroscience 2021; (15()):648743 doi:10.3389/fnins.2021.648743.

    PMID: 33776643
  18. 18

    Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons.

    Shi Y, Lin S, Staats KA, et al.

    Nature medicine 2018; (24(3)):313-325 doi:10.1038/nm.4490.

    PMID: 29400714
  19. 19

    Blocking RAN translation without altering repeat RNAs rescues C9ORF72-related ALS and FTD phenotypes.

    Jiang X, Schaeffer L, Patni D, et al.

    Science (New York, N.Y.) 2026; (391(6785)):eadv2600 doi:10.1126/science.adv2600.

    PMID: 41643021
  20. 20

    An update on genetic frontotemporal dementia.

    Greaves CV, Rohrer JD

    Journal of neurology 2019; (266(8)):2075-2086 doi:10.1007/s00415-019-09363-4.

    PMID: 31119452
  21. 21

    High levels of neurofilament light and YKL-40 in cerebrospinal fluid are related to poor outcome in ALS.

    Rosén C, Mitre B, Nellgård B, et al.

    Journal of the neurological sciences 2024; (463()):123112 doi:10.1016/j.jns.2024.123112.

    PMID: 38972199

This page explains FTD-ALS diagnostic testing for informational purposes only and does not constitute medical advice. A neurologist and genetic counselor should interpret your symptoms, test results, and genetic findings in context.

Get notified when new evidence is published on Frontotemporal dementia with motor neuron disease.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.