Gait and Balance Impairment in Rare and Very Rare Neurological Diseases (GALVANISE)

Rare and very rare neurological diseases primarily or exclusively affect the nervous system with a prevalence of < 5 out of 10'000 and 100'000 people, respectively. Besides these, there are undiagnosed neurological diseases: neurological conditions without a diagnosis after completing a full diagnostic examination.

Rare, very rare, and undiagnosed neurological diseases are complicated and progressive and often cause variegated motor signs, impairments, and syndromes.

Balance and gait are frequently affected in these conditions, already at the clinical examination. These balance and gait impairments limit activities and cause an increased risk of falling. Falls can eventually result in injuries, even severe.

There are only a few studies about these diseases, likely because of their rarity. Hence, the clinical presentation and the course of rare and very rare diseases are poorly known or even unknown. Essential information for these conditions' diagnosis, prognosis, treatment and rehabilitation is missing.

MaNeNeND is an observational study underway at the Fondazione IRCCS Istituto Neurologico "Carlo Besta" (Milano) aimed at detailing the clinical and biological features of very rare and undiagnosed neurological diseases.

Research questions:

1. Do patients with rare (Ra), very rare (V) and undiagnosed (U) neurological diseases suffer a balance and gait impairment?
2. Is there a correlation between the clinical and instrumental severity of the balance and gait impairment in RaVU neurological diseases?
3. Are instrumental measures more sensitive in detecting balance and gait impairments in patients affected by a RaVU neurological disease than the clinical measures?
4. Do the balance and gait impairments in RaVU neurological diseases worsen in time?

The current project aims at diagnosing, quantifying and detailing the balance and gait impairment in rare, very rare and undiagnosed neurological diseases.

To this aim, questionnaires, clinical scales and instrumental tests will be administered to these patients to collect a wide range of balance and gait measures.

These measures will also integrate those collected with MaNeNeND to provide a more detailed description of patients with rare, very rare and diagnosed neurological diseases.

Participants will complete two questionnaires: the Dizziness Handicap Inventory - short form (DHI-sf, an ordinal score of self-perceived balance) and the Modified Fatigue Impact Scale (MFIS, an ordinal score of self-perceived fatigue).

Moreover, a clinician will administer the Mini Balance Evaluation Systems Test (Mini-BESTest, an ordinal score of balance), the 10 m walking test (for measuring the gait speed and other gait parameters) and the Timed Up and Go test (an instrumental measure of mobility and balance). Walking and the Timed Up and Go tests will be recorded with a trunk-worn inertial measurement unit.

Finally, participants will be asked to complete an instrumental upright stance and gait assessment, the first consisting of standing on posturographic plates and the second of walking on a treadmill equipped with force sensors. When walking on the treadmill, an optoelectronic system will also record the position in time of limbs and trunk.

The quantification of the severity of the balance and gait impairment of the patients suffering a rare, very rare or undiagnosed neurological disease will highlight these persons' therapeutic and rehabilitative needs.

Comparing the balance and gait impairment of rare, very rare and undiagnosed diseases with those of multiple sclerosis, Parkinson's disease and peripheral neuropathy will highlight if the formers' balance and gait impairment has unique characteristics that could help ease the diagnosis of these uncommon conditions.

The longitudinal measurements on rare, very rare and undiagnosed diseases will be paramount to identifying prognostic factors.

In addition, the data collected in the current study will be crucial for future studies, for example, for estimating the sample size in clinical trials.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Healthy; Parkinson Disease; Healthy Aging; Peripheral Neuropathy; Rare Diseases
• Intervention / Treatment: Other: Questionnaires, clinical scales and instrumental tests

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy
    • Active, not recruiting
    • IRCCS Istituto Neurologico Carlo Besta
  • Milan
    • Milano, Milan, Italy
      • Recruiting
      • IRCCS Istituto Auxologico Italiano
      • Contact: Antonio Caronni, MD, PhD; Phone Number: 02 619111; Email: a.caronni@auxologico.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with a balance and gait impairment secondary to multiple sclerosis, Parkinson's disease, peripheral neuropathy of the lower limbs, a rare, ultrarare or undiagnosed neurological disease.

A group of age-matched controls will also be recruited.

Description

Inclusion criteria

• Multiple sclerosis, Parkinson's disease, peripheral neuropathy of the lower limbs or rare or ultrarare neurological disease (e.g. la Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome - CANVAS, ORPHAcode: 504476; Wilson's disease, ORPHAcode: 905)
• undiagnosed neurological disease, i.e. a neurological disease that remains unknown after a full diagnostic assessment;
• age > 18 years;
• ability to stand upright with no assistance and no assistive device for > 30 seconds;
• ability to walk without assistance and with no assistive device for > 50 m;
• ability to give their informed consent.

Exclusion criteria

• pregnancy or breastfeeding
• any other medical conditions affecting by itself balance and gait (e.g. lower limb amputation, hemiparesis due to a stroke)
• major orthopaedic surgery (e.g. hip or knee replacement).

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy controls	Other: Questionnaires, clinical scales and instrumental tests; Questionnaires, clinical scales and instrumental tests to collect a wide range of balance and gait measures.
Parkinson's disease patients	Other: Questionnaires, clinical scales and instrumental tests; Questionnaires, clinical scales and instrumental tests to collect a wide range of balance and gait measures.
Multiple sclerosis patients	Other: Questionnaires, clinical scales and instrumental tests; Questionnaires, clinical scales and instrumental tests to collect a wide range of balance and gait measures.
Peripheral neuropathies of the lower limbs	Other: Questionnaires, clinical scales and instrumental tests; Questionnaires, clinical scales and instrumental tests to collect a wide range of balance and gait measures.
Rare and ultrarare neurological diseases	Other: Questionnaires, clinical scales and instrumental tests; Questionnaires, clinical scales and instrumental tests to collect a wide range of balance and gait measures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Balance (Mini-BESTest)	Mini Balance Evaluation Systems Test (Mini-BESTest, an ordinal score of balance)	At enrollment
Balance (Timed Up and Go test)	Timed Up and Go test instrumented with inertial sensors	At enrollment
Gait speed	10 m walking test	At enrollment
Gait analysis - kinematic - stride length	Stride length, right step length and left step length	At enrollment
Gait analysis - kinematic - duration	Stride duration, right and left step duration	At enrollment
Gait analysis - kinematic - width of the base of support	Width of the base of support	At enrollment
Gait analysis - kinematic - dorsal ankle angle	Dorsal ankle angle	At enrollment
Gait analysis - dynamic - reaction force	Anterior-posterior, mediolateral and vertical reaction force	At enrollment
Gait analysis - dynamic - ankle power	Right and left ankle power	At enrollment
Gait analysis - dynamic - energy	Potential and kinetic energy of the body centre of mass	At enrollment
Posturography - static - centre of pressure position	Centre of pressure position while standing	At enrollment
Posturography - static - centre of mass position	Centre of mass position while standing	At enrollment
Posturography - dynamic - centre of pressure position	Centre of pressure position after base of support perturbations	At enrollment
Posturography - dynamic - centre of mass position	Centre of mass position after base of support perturbations	At enrollment

Collaborators and Investigators

• Sponsor: Istituto Auxologico Italiano
• Collaborators: IRCCS Istituto Neurologico Carlo Besta

Publications and helpful links

General Publications

• Ganz DA, Bao Y, Shekelle PG, Rubenstein LZ. Will my patient fall? JAMA. 2007 Jan 3;297(1):77-86. doi: 10.1001/jama.297.1.77.
• Reinhard C, Bachoud-Levi AC, Baumer T, Bertini E, Brunelle A, Buizer AI, Federico A, Gasser T, Groeschel S, Hermanns S, Klockgether T, Krageloh-Mann I, Landwehrmeyer GB, Leber I, Macaya A, Mariotti C, Meissner WG, Molnar MJ, Nonnekes J, Ortigoza Escobar JD, Perez Duenas B, Renna Linton L, Schols L, Schuele R, Tijssen MAJ, Vandenberghe R, Volkmer A, Wolf NI, Graessner H. The European Reference Network for Rare Neurological Diseases. Front Neurol. 2021 Jan 14;11:616569. doi: 10.3389/fneur.2020.616569. eCollection 2020.
• Vieira ER, Palmer RC, Chaves PH. Prevention of falls in older people living in the community. BMJ. 2016 Apr 28;353:i1419. doi: 10.1136/bmj.i1419. No abstract available.
• Caronni A, Sterpi I, Antoniotti P, Aristidou E, Nicolaci F, Picardi M, Pintavalle G, Redaelli V, Achille G, Sciume L, Corbo M. Criterion validity of the instrumented Timed Up and Go test: A partial least square regression study. Gait Posture. 2018 Mar;61:287-293. doi: 10.1016/j.gaitpost.2018.01.015. Epub 2018 Jan 31.
• Caronni A, Gervasoni E, Ferrarin M, Anastasi D, Brichetto G, Confalonieri P, Di Giovanni R, Prosperini L, Tacchino A, Solaro C, Rovaris M, Cattaneo D, Carpinella I. Local Dynamic Stability of Gait in People With Early Multiple Sclerosis and No-to-Mild Neurological Impairment. IEEE Trans Neural Syst Rehabil Eng. 2020 Jun;28(6):1389-1396. doi: 10.1109/TNSRE.2020.2991636. Epub 2020 Apr 30.
• Scarano S, Sansone VA, Ferrari Aggradi CR, Carraro E, Tesio L, Amadei M, Rota V, Zanolini A, Caronni A. Balance impairment in myotonic dystrophy type 1: Dynamic posturography suggests the coexistence of a proprioceptive and vestibular deficit. Front Hum Neurosci. 2022 Jul 28;16:925299. doi: 10.3389/fnhum.2022.925299. eCollection 2022.
• Scarano S, Rota V, Tesio L, Perucca L, Robecchi Majnardi A, Caronni A. Balance Impairment in Fahr's Disease: Mixed Signs of Parkinsonism and Cerebellar Disorder. A Case Study. Front Hum Neurosci. 2022 Mar 9;16:832170. doi: 10.3389/fnhum.2022.832170. eCollection 2022.
• The Lancet Neurology. Rare neurological diseases: a united approach is needed. Lancet Neurol. 2011 Feb;10(2):109. doi: 10.1016/S1474-4422(11)70001-1. No abstract available.
• Picardi M, Redaelli V, Antoniotti P, Pintavalle G, Aristidou E, Sterpi I, Meloni M, Corbo M, Caronni A. Turning and sit-to-walk measures from the instrumented Timed Up and Go test return valid and responsive measures of dynamic balance in Parkinson's disease. Clin Biomech (Bristol). 2020 Dec;80:105177. doi: 10.1016/j.clinbiomech.2020.105177. Epub 2020 Sep 18.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2023
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: March 8, 2024
• First Submitted That Met QC Criteria: March 26, 2024
• First Posted (Actual): April 2, 2024

Study Record Updates

• Last Update Posted (Actual): August 3, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Balance; Gait analysis; Risk of falling; Posturography; Rare neurological diseases; Very rare neurological diseases; Undiagnosed neurological diseases; Upright stance
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Multiple Sclerosis; Rare Diseases; Peripheral Nervous System Diseases; Parkinson Disease; Nervous System Diseases
• Other Study ID Numbers: 24C302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The database will be made available upon request on Zenodo.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No