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General aim of the study is the improvement of the clinical knowledge of ultra-rare inherited metabolic and degenerative neurological diseases (prevalence less than 5:100,000) in adulthood through the systematic longitudinal collection of clinical, laboratory and instrumental data.
The study provides a collection of retrospective data from adult patients with ultra-rare inherited neurological diseases followed at "Carlo Besta" Neurological Institute from 1st January 2004 until March 2021. Further, prospective data will be collected starting from March 2021 (date of protocol approval) and spanning the next ten years. Normal clinical practice will be followed for collection of the prospective data. Follow-up assessment will be performed at least once a year to evaluate the disease course. Based on their clinical manifestations, patients will be assessed by using quantitative functional tests (clinimetric tests such as Timed Up and Go Test) and traditional ordinal scales (such as the scale for the assessment and rating of ataxia (SARA). Moreover, a varying of laboratory and instrumental tests (e.g., neuroimaging, neurophysiological investigations, etc.) will be used according to clinical practice in selected patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Retrospective study | collection of retrospective data from adult patients with ultra-rare inherited neurological diseases |
| |
| Prospective study | prospective data will be collected starting from March 2021 (date of protocol approval) and spanning the next ten years |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| collection of data | Other | collection of retrospective and prospective data from adult patients with ultra-rare inherited neurological diseases |
|
| Measure | Description | Time Frame |
|---|---|---|
| Verbal (letter) fluency | Repeated Montreal Cognitive Assessment (MoCA) letter F fluency subtest | 10 years |
| Stance and gait performances [Time Frame: 10 years] Stance and gait performances | Repeated SARA (Scale for the Assessment and Rating Ataxia) stance subtask, ambulation index (AI) and Timed Up and Go (TUG) test | 10 years |
| Upper limb motor function | Repeated ONLS (Overall Neuropathy Limitation Scale) arm scale | 10 years |
| Swallowing function (dysphagia) | Repeated NP-C mDRS (Niemann-Pick type C modified disability rating scale) swallowing scale | 10 years |
| Speech function (dysarthria) | Repeated NP-C mDRS language scale | 10 years |
| Bladder function | Repeated AADS (Adult Adrenoleukodystrophy Disability Score) Bladder function scale | 10 years |
| Sleep | Repeated assessment of presence or absence of sleep disturbances | 10 years |
| Quality of life | Repeated EuroQol-5D-5L (EQ-5D-5L) questionnaire |
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Inclusion Criteria:
Exclusion Criteria:
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Adults with ultra-rare inherited degenerative and metabolic neurological diseases
Adults with undiagnosed neurological diseases (when supposed to be inherited)
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ettore Salsano, MD | Contact | +39022394 | 3001 | ettore.salsano@istituto-besta.it |
| Renato Mantegazza, MD | Contact | +39022394 | 2321 | crc@istituto-besta.it |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fondazione IRCCS Istituto Neurologico Carlo Besta | Recruiting | Milan | Milano | 20133 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41667276 | Derived | Benzoni C, Moscatelli M, Lanteri P, Pensato V, Calo C, Allievi S, Gellera C, Ardissone A, Moroni I, Fenu S, Cavalca E, Pareyson D, Salsano E. Adrenoleukodystrophy in adults: phenotypic characterisation and natural history in a large cohort. J Neurol Neurosurg Psychiatry. 2026 May 14;97(6):483-492. doi: 10.1136/jnnp-2025-337540. | |
| 37782421 |
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| 10 years |
| Moscatelli M, Benzoni C, Doniselli FM, Verri M, Pascuzzo R, Aquino D, Mazzi F, Erbetta A, Salsano E. Interval between contrast administration and T1-weighted MRI for cerebral adrenoleukodystrophy: a single-case observation. Eur Radiol Exp. 2023 Oct 2;7(1):57. doi: 10.1186/s41747-023-00373-6. |
| ID | Term |
|---|---|
| D030342 | Genetic Diseases, Inborn |
| D035583 | Rare Diseases |
| D008659 | Metabolic Diseases |
| D000080842 | Undiagnosed Diseases |
| D009422 | Nervous System Diseases |
| D000326 | Adrenoleukodystrophy |
| D007966 | Leukodystrophy, Metachromatic |
| D007965 | Leukodystrophy, Globoid Cell |
| D038261 | Alexander Disease |
| C536329 | Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy |
| D056784 | Leukoencephalopathies |
| D020371 | Pelizaeus-Merzbacher Disease |
| D003560 | Cysts |
| C535306 | 2-Hydroxyglutaricaciduria |
| C537359 | Methylmalonic acidemia with homocystinuria |
| C536275 | Fahr's disease |
| D006527 | Hepatolenticular Degeneration |
| D019294 | Xanthomatosis, Cerebrotendinous |
| D013106 | Sphingolipidoses |
| ID | Term |
|---|---|
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009750 | Nutritional and Metabolic Diseases |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D020279 | Hereditary Central Nervous System Demyelinating Diseases |
| D003711 | Demyelinating Diseases |
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D040181 | Genetic Diseases, X-Linked |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D008661 | Metabolism, Inborn Errors |
| D018901 | Peroxisomal Disorders |
| D000309 | Adrenal Insufficiency |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
| D052516 | Sulfatidosis |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D052439 | Lipid Metabolism Disorders |
| D019636 | Neurodegenerative Diseases |
| D009369 | Neoplasms |
| D020763 | Pathological Conditions, Anatomical |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D001480 | Basal Ganglia Diseases |
| D009069 | Movement Disorders |
| D008664 | Metal Metabolism, Inborn Errors |
| D014973 | Xanthomatosis |
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