Amyotrophic lateral sclerosis spatial epidemiology in the Mount Etna region, Italy

Previously, we described a significantly
higher risk of amyotrophic lateral sclerosis
(ALS) among the population living
on the eastern flank of Mount Etna with
respect to the western flank [relative risk
2.75; 95% confidence interval (CI) 1.64–
4.89] [1]. Since winds usually blow Etna
ash from west to northwest [2], the eastern
flank is the most exposed area and
volcanogenic metals were proposed as a
possible explanation.
Here, we further investigated the spatial
distribution of ALS cases in the
Mount Etna region during 2005–2015,
performing a geostatistical cluster analysis.
The study was conducted in the province
of Catania. ALS patients were
diagnosed according to the El Escorial
revised criteria [3]. Standardized incidence
ratios (SIRs) of each communality
were calculated using the annual population
of the entire province as a reference
through an age- and sex-adjusted indirect
standardization. Cluster analysis was
performed using both a local Moran
index (also termed Local Indicators of
Spatial Association, LISA) [4] and Kulldorff’s
spatial scan statistics [5]. The
Monte Carlo simulation was used to
assess the statistical significance of the
results (P value was set at 0.05%). The
Kulldorff spatial scan statistic was implemented
using SatScan software, version
9.4.4 [6].
A total of 202 residents were diagnosed
with ALS during 2005–2015 giving
a mean annual crude incidence rate of
1.70/100 000 person-years (95% CI 1.47–
1.94) (Table S1). Two communalities,
both located on the southeastern flank of
the volcano, showed an SIR higher than
1 (SIR 1.80, 95% CI 1.07–2.84, and SIR
2.28, 95% CI 1.18–3.99) (Fig. 1a). LISA
analysis showed the presence of an
aggregative spatial structure on the
southeastern flank of Mount Etna and
Kulldorff’s statistic confirmed the above
indication by revealing a higher incidence
spatio-temporal cluster that includes 13
communalities in the same area. During
the 2006–2010 period, 13.24 cases were
expected whereas 33 were observed,
therefore resulting in an SIR of 2.49
(95% CI 1.72–3.50, P value 0.007)
(Fig. 1b). Purely spatial analysis revealed
a smaller cluster including four communalities,
with an SIR of 2.2 (95% CI
1.39–3.3) (Fig. 1b).
Several genetic and environmental factors
have been proposed to play a role in
the ALS pathogenesis. Among environmental
factors, metals seem to play a relevant
role [7]. Volcanoes are a major source
of metals [8] and Mount Etna is the largest
active volcano in Europe. We found a
higher incidence spatio-temporal cluster
(2006–2010) on the southeastern flank of
the volcano, the area most exposed to volcanic
ash. In fact, during 2001–2003 an
intense and long-lasting explosive activity
ofMount Etna was recorded from eruptive
fissures located on the southern and the
eastern flanks of the volcano and during
this period about 2.1 kg/m2 of ash was
deposited in 3 days [9].
This finding could further suggest the
possible role of volcanogenic metals in
ALS pathogenesis. Nonetheless, we cannot
exclude that other factors, both
genetic and environmental, may have
contributed to the higher incidence of
ALS on the southeastern flank of Mount
Etna. Further studies are needed in order
to explore possible alternative hypotheses.

1. Nicoletti A, Vasta R, Venti V, et al. The
epidemiology of amyotrophic lateral sclerosis
in the Mount Etna region: a possible
pathogenic role of volcanogenic metals. Eur
J Neurol 2016; 23: 964–972.
2. Calabrese S, Aiuppa A, Allard P, et al.
Atmospheric sources and sinks of volcanogenic
elements in a basaltic volcano
(Etna, Italy). Geochim Cosmochim Acta
2011; 75: 7401–7425.
3. Brooks BR, Miller RG, Swash M, et al. El
Escorial revised criteria for the diagnosis of
amyotrophic lateral sclerosis. Amyotroph
Lateral Scler Motor Neuron Disord 2000; 1:
293–299.
4. Moran PA. Notes on continuous stochastic
phenomena. Biometrika 1950; 37: 17–23.
5. Kulldorff M. A spatial scan statistic. Commun
Stat Theory Methods 1997; 26: 1481–
1496.
6. SaTScan – Software for the spatial, temporal,
and space–time scan statistics [online].
https://www.satscan.org/. (accessed 6/6/
2017).
7. Cicero CE, Mostile G, Vasta R, et al.
Metals and neurodegenerative diseases. A
systematic review. Environ Res 2017; 159:
82–94.
8. Hansell AL, Horwell CJ, Oppenheimer C.
The health hazards of volcanoes and
geothermal areas. Occup Environ Med 2006;
63: 149–156.
9. Branca S, Carlo PD. Types of eruptions of
Etna volcano AD 1670–2003: implications
for short-term eruptive behaviour. Bull Volcanol
2005; 67: 732–742.