Early Dropped Head Syndrome Is More Prevalent in C9orf72 and FUS/TLS ALS

Area of Science:

• Neurology
• Genetics
• Oncology

Background:

• Dropped head syndrome (DHS) is a common symptom in late-stage amyotrophic lateral sclerosis (ALS).
• Its occurrence as an early symptom in genetic ALS cohorts is less understood.
• Investigating DHS as a prognostic factor in early-stage ALS is crucial.

Purpose of the Study:

• To determine the frequency of DHS in a genetic ALS cohort with pathogenic variants.
• To assess if DHS, particularly early DHS (EDHS), is a prognostic factor for survival.
• To explore the correlation between specific gene mutations and DHS prevalence.

Main Methods:

• Collected data on pathogenic variants (PV), sex, age at onset, and survival times.
• Classified DHS as early (EDHS) if appearing within 12 months of ALS onset, or late (LDHS).
• Utilized age-adjusted Cox regression to analyze survival data.

Main Results:

• DHS was observed in 62 of 93 genetic ALS patients.
• Prevalence varied by gene: 72.1% in C9orf72, 52.9% in SOD1, 100% in FUS/TLS.
• Early DHS (EDHS) occurred in 16 patients, predominantly with C9orf72 and FUS/TLS.
• DHS significantly increased mortality risk (Hazard Ratio 11.63).

Conclusions:

• DHS is more frequent in C9orf72 and FUS/TLS genetic ALS.
• DHS is a significant risk factor for reduced survival in ALS.
• Early onset DHS is particularly associated with poorer prognosis.