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Background: To study gait is of great importance for the health of the aging population. Higher-level gait disorders (HLGD) are characterized by a slow, symmetrical, unsteady gait. Its cause is most often unknown. HLGD in combination with ventriculomegaly (i.e., large brain ventricles) is obligatory for the diagnosis of Idiopathic Normal pressure hydrocephalus (INPH), a syndrome that is sometimes treatable with insertion of a CSF shunt. It is therefore important to investigate the prevalence of HLGD in the population and brain morphometry in individuals with HLGD. Further, self-perceived confidence in gait and balance among patients with HLGD and INPH is unknown and important to study as slow gait velocity is associated with falls, injuries, and death. CSF shunts in INPH are associated with adverse events and little is known about epilepsy after surgery or minor and moderate adverse events such as headache and abdominal pain.

Objective: In the older population investigate the prevalence of HLGD, and its association to ventriculomegaly. To investigate quality of life (QoL), depressive symptoms, and balance confidence in an HLGD population. In patients shunted for INPH, assess falls, fear of falling, balance confidence and prevalence of the possible adverse events headache, epilepsy, and abdominal pain after shunt surgery. 

Methods: Two population-based case-controlled cohorts were studied. In the first study, the "Ventriculomegaly and gait disturbance in the senior population in the region of Västerbotten" (VESPR) study, individuals (65-84 years) were recruited through a questionnaire (n=6467 dispatched). The final population consisted of 798 cases with gait disorders and 249 controls without gait disorders, age- and sex-matched to individuals with HLGD. All had been examined by a physician and were categorized: 1. "HLGD"; 2. "neurological gait disorder"; 3. "non-neurological gait disorder" or; 4. "no gait disorder". Participants were assessed with: the Swedish modification of the Falls-Efficacy Scale (FES(S)), the Modified Gait-Efficacy Scale (mGES), the Euro Quality of Life 5-Dimension 5-Level (EQ5D5L) instrument (EQ5D5L index and Euro Quality of life visual analogue scale (EQ VAS)) and the Geriatric depression scale 15 (GDS-15). Cases and controls had an MRI of the brain and ventricular size was measured. 

The second study, the "Comorbidities and vascular risk factors associated with idiopathic normal pressure hydrocephalus" (INPH-CRasH) study, consisted of 176 shunted INPH patients and 368 age- and sex-matched controls. Mean age was 74 years in INPH and 73 in controls. All had a visit to a healthcare facility. Information regarding adverse events, falls and fear of falling were gathered through a questionnaire. Additional information on diagnoses and prescribed drugs were obtained from the Swedish national patient- and drug registries. Data was compared between the groups, and before- and after surgery for INPH. 

Results: In the VESPR study, 87 individuals were categorized as HLGD, corresponding to a prevalence of 5.8% (95% confidence interval (CI) 4.6-7.0) in the older population. A definite cause was found in 13% (n=11) of individuals with HLGD, but ventriculomegaly was present in 63% (n=46/73, controls: 38%, n=70/184; OR 2.8 95% CI 1.6-4.9, p<0.001). HLGD had more depressive symptoms and lower quality of life (QoL), compared with individuals without gait disorder (GDS-15: 3.9±3.4 vs. 2.5±2.8, p=0.004; EQ VAS: 63±17 vs. 71±18; p<0.001; EQ5D5L index: 0.671±0.188 vs. 0.840±0.126, p<0.001). HLGD had low confidence in gait and to avoid falls compared to those without gait disorder (mGES: 60±22 vs. 74±21; p<0.001; FES(S): 93±32 vs. 111±25 p<0.001). 

The INPH-CRasH study revealed that patients with INPH feared falling more often (3.3±1.1) and had lower balance confidence (78±40) than controls (fear of falling: 1.6±0.9, balance confidence: 126±14; p<0.001 in both comparisons). After surgery, the proportions were reduced in INPH (p<0.001). More INPH than controls were fallers (before surgery: 67% vs. 11% OR 15.48 95% CI 9.85-24.32; after surgery: 35% vs 11% OR 4.15 95% CI 2.65-6.50, p<0.001). The proportion was reduced after surgery (p<0.001). In shunted INPH, epilepsy, antiepileptic drug (AED) treatment and headache was more common than in controls (epilepsy: 4.5% vs. 1.1% OR 4.3, 95% CI 1.3-14.6, p=0.023; AED treatment: 14.8% vs. 7.3% OR 0.5 95% CI 0.3-0.8, p=0.010; headache: 36.1% vs 11.6% OR 0.2 95% CI 0.2-0.4, p<0.001). Forty percent INPH (n=70) had abdominal pain after surgery. 

Conclusions: HLGD was common in the general older population and associated to ventriculomegaly. HLGD was also associated with low quality of life and depressive symptoms. Both individuals with HLGD and patients with INPH had low confidence in their balance but it was less common after surgery for INPH. However, patients shunted for INPH still had more problems with low balance confidence, falls, and fear of falling than controls. After shunt surgery for INPH, a significant portion of patients developed epilepsy, headache, and abdominal pain. The findings motivate investigations of causal relationships between HLGD and ventriculomegaly and if treatment options exist for HLGD. The observed adverse events in patients shunted for INPH should be considered in pre- and postoperative evaluations of shunt surgery, and in the development of new techniques for shunt placement. Additional interventions directed towards low balance confidence, falls and fear of falling should be considered for patients with INPH, and for individuals with HLGD.