Among the 782 cases the incidence of falls from disease onset to death was 77.5%. It was highest in CBD (100%) and PSP (97.5%) and lowest in MSA (77.6%) and PD (73.3%) (table 1).
Table 1Characteristics of patients according to pathological diagnosis
Falls occurred earlier in those with PSP (median 17 months; range 0–244 months) than all other diseases (fig 1). Median time to first fall was significantly shorter in RS (12; range 0–95) compared to both PSP‐P (47; 0–228, p<0.001), PD (108; 0–384, p<0.001), and MSA (42; 0–165). In PD univariable analysis showed an association between the occurrence of falls and the late clinical features of cognitive dysfunction, speech disturbance, dysphagia, autonomic dysfunction, and hallucinations and a negative association between the falls and early and late tremor (table 2).
Figure 1Latency to first fall according to disease, showing interquartile range.
Table 2Clinical features in fallers and non‐fallers: percentage, χ2
In PSP, early falls (within the first two years of disease) were associated with symmetrical disease onset and early cognitive dysfunction, axial rigidity, postural instability, eye movement abnormalities, and speech disturbance (occurring within two years of disease onset). In common with PD, in those with early falls tremor was less frequent. In MSA falls at any time were associated with the late clinical features of limb rigidity, speech disturbance, dysphagia, and pyramidal tract signs. There were no significant associations between falls and clinical features in VP, DLB, CBD, and AD; this may be due to the small sample sizes for these diseases.
Multivariate analyses were performed using the Cox multiple stepwise regression model on early clinical features, age, and gender identified several clinical factors which independently influence time to first fall (table 3).
Table 3Factors affecting time to first fall in PD, PSP and MSA: independent predictors from Cox multiple regression analysis on early clinical features, age and sex
In PD female gender, older age, symmetrical onset, and autonomic dysfunction were all independent predictors of earlier falls. Age of onset was also an important independent factor predicting time to first fall in PSP and MSA as was postural instability.
Almost all patients with PSP had falls at some point in their clinical history; patients with falls in the first two years had mean life expectancy 3.3 years lower than other PSP patients (table 4).
Table 4Disease duration (time from onset until death) and age at onset in early (<2 years) and late (>2 years) fallers in PSP, RS, and PSP‐P (Mann‐Whitney U test)
This difference was greater in the PSP‐P group, and there was no difference in the RS group. This is illustrated graphically by the Kaplan‐Meier plot (fig 2).
Figure 2Kaplan‐Meier plot illustrates the effect of early or late falls upon survival in 124 cases of (A) PSP in total, and separated into subgroups; (B) RS (72 cases); and (C) PSP‐P (54 cases).
There were 166 fractures recorded in 134 (17.1%) patients. Eighty patients (16.9%) with PD sustained a total of 96 fractures, 36 (28.6%) patients with PSP sustained 52 fractures, and 10 (11%) patients with MSA sustained a fracture.
Hip fractures comprised 46.9% of all fractures in PD and one third of fractures occurred in the upper limb. In PSP the proportion of hip fractures was less than in PD (30.7% v
test), and the proportion of “other upper limb fractures” (including the clavicle, scapula, and bones in the hand) was higher than in PD (p
test) (table 5). Comparing all patients (with and without fractures), multiple fractures were significantly more common in PSP than in both PD (6.4% v
test) and MSA (6.4% v
test). Skull fractures (3.2% v
test) and truncal fractures (5.6% v
test) were both more common in PSP than in PD. There were no substantial or significant differences in fracture site between the two subgroups of PSP.
Table 5Distribution of fracture location in bradykinetic rigid syndromes: number (% of all fractures)
The clinical features that were significantly associated with fractures in PD were early falls (9.3% with fractures v
3.2% no fractures, χ2
0.024), late falls (100% v
p<0.001), and late postural instability (88.4% v
0.003)); in PD fractures were also more frequent in women (28.6% v
p<0.001). In PSP early bradykinesia (77.8% with fractures v
92% without fractures, χ2
0.027), early limb rigidity (47% v
0.028), and early pyramidal signs (2.5% v
0.02) occurred less frequently in those with fractures. Sex distribution was not significantly different between fracture and non‐fracture groups in PSP (34% women and 44% women respectively, χ2
0.275). In contrast, women were overrepresented in the 10 MSA patients with fractures (90% v
0.015). None of the three VP patients with fractures had either bradykinesia (0% v
71% in VP patients without fractures, χ2
0.017) or limb rigidity (0% v
85% , χ2