Phenotypic variability in ALS-FTD and effect on survival

We thank Dr. Abe for his interest in our study¹ that investigated survival in amyotrophic lateral sclerosis-frontotemporal dementia (ALS- FTD) patients. Specific comparison of motor and cognitive presentations in ALS-FTD established that patients with a motor-onset of their disease had reduced survival—which was associated with increased motor cortex atrophy—suggesting that survival may be mediated by motor function and other critical physiological aspects.

We agree that ALS-FTD can present with behavioral and cognitive changes, as has been documented in well-characterized case series.^2–4

A key aim of the present study was to understand how this cognitive, behavioral profile differs from behavioral variant frontotemporal dementia (bvFTD). We found that those with ALS-FTD with an initial cognitive presentation have more prominent language changes and both ALS-FTD motor and cognitive presentation have greater deficits in emotion processing than bvFTD—which is a new finding and requires further investigation—as traditionally bvFTD has been regarded as having the greatest emotion processing deficits.⁵

Further studies are currently underway to better dissect the presentations and phenotypes across the ALS-FTD spectrum. Such studies should include both clinical, structural, functional, and pathological evaluation to better characterize the commonalities and differences across the ALS-FTD spectrum.

Disclosure

The authors report no relevant disclosures. Contact [email protected] for full disclosures.

References

1. Ahmed RM, Devenney EM, Strikwerda-Brown C, Hodges JR, Piguet O, Kiernan MC. Phenotypic variability in ALS-FTD and effect on survival. Neurology 2020 Epub Apr 10.
2. Burrell JR, Halliday GM, Kril JJ, et al. The frontotemporal dementia-motor neuron disease continuum. Lancet 2016;388:919–931.
3. Lillo P, Mioshi E, Zoing MC, Kiernan MC, Hodges JR. How common are behavioural changes in amyotrophic lateral sclerosis? Amyotroph Lateral Scler 2011;12:45–51.
4. Saxon JA, Thompson JC, Jones M, et al. Examining the language and behavioural profile in FTD and ALS-FTD. J Neurol Neurosurg Psychiatry 2017;88:675–80.
5. Kumfor F, Piguet O. Disturbance of emotion processing in frontotemporal dementia: a synthesis of cognitive and neuroimaging findings. Neuropsychol Rev 2012;22:280–97.

I read the article by Ahmed et al.¹ and generally agree with their comments. However, I offer some insights.

First, Yuasa² reported a case of amyotrophic lateral sclerosis (ALS) with dementia who presented impairment of personality, forgetfulness, and forced grasp before presenting muscle weakness. The patient showed brain atrophy in the frontal lobe. Following reports—including autopsies and neuroimages that supported ALS with dementia or motor neuron disease (MND) with dementia—showed atrophy, reduced blood flow, or hypometabolism characterized demonstrated in the central region and in the frontal lobe. The authors suggested that emotion processing and behavior disturbance had been considered core deficits in behavioral variant frontotemporal dementia (bvFTD) and thought to be less prominent in ALS-FTD. However, other studies including Yuasa’s suggested behavioral changes in ALS-FTD patients in their early stages. To elucidate these differences, morphological study does not have enough power, but functional imaging studies may hold advantages.³ We studied ALS patients with dementia by using SPECT and concluded ALS and ALS with dementia made a wide spectrum of a disease.⁴ The authors’ indication of atrophy in the dorsolateral prefrontal cortex (DLPFC) might be a key for differential diagnoses of variant types of ALS-FTD. I recently experienced an ALS-FTD patient who showed dominant bulbar palsy with forgetfulness but preserved personality. His SPECT showed reduced uptake in the central and prefrontal cortex not in the DLPFC.

I agree that further studies of ALS, ALS-FTD, and bvFTD are needed, but I suggest that function studies should be included in future projects.

Disclosure

The author reports no relevant disclosures. Contact [email protected] for full disclosures.

References

1. Ahmed RM, Devenney EM, Strikwerda-Brown C, Hodges JR, Piguet O, Kiernan MC. Phenotypic variability in ALS-FTD and effect on survival. Neurology 2020 Epub Apr 10.
2. Yuasa R. Amyotrophic lateral sclerosis with organic dementia: report of a case. Clin Neurol (Tokyo) 1964;4:529–534.
3. Saxon JA, Thompson JC, Jones M, et al. Examining the language and behavioural profile in FTD and ALS-FTD. J Neurol Neurosurg Psychiatry 2017;88:675–680.
4. Abe K, Fujimura H, Toyooka K, T Hazama, Hirono N, Yorifuji S, Yanagihara T. Single-photon emission computed tomographic investigation of patients with motor neuron disease. Neurology 1993;43:1569–1573.