OBJECTIVE: To characterize ocular motor function in patients with Niemann-Pick disease type C (NPC). METHODS: In a multicontinental, cross-sectional study we characterized ocular-motor function in 72 patients from 12 countries by video-oculography. Interlinking with disease severity, we also searched for ocular motor biomarkers. Our study protocol comprised reflexive and self-paced saccades, smooth pursuit, and gaze-holding in horizontal and vertical planes. Data were compared with those of 158 healthy controls (HC). RESULTS: Some 98.2% of patients generated vertical saccades below the 95% CI of the controls' peak velocity. Only 46.9% of patients had smooth pursuit gain lower than that of 95% CI of HC. The involvement in both downward and upward directions was similar (51°/s (68.9, [32.7-69.3]) downward versus 78.8°/s (65.9, [60.8-96.8]) upward). Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit correlated best to disease severity. Compensating strategies such as blinks to elicit saccades, and head and upper body movements to overcome the gaze palsy, were observed. Vertical reflexive saccades were more impaired and slower than self-paced ones. Gaze-holding was normal. Ocular-motor performance depended on the age of onset and disease duration. CONCLUSIONS: This is the largest cohort of NPC patients investigated for ocular-motor function. Vertical supranuclear saccade palsy is the hallmark of NPC. Vertical upward and downward saccades are equally impaired. Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit can be used as surrogate parameters for clinical trials. Compensating strategies can contribute to establishing a diagnosis.

• MeSH
• lidé MeSH
• Niemannova-Pickova nemoc typu C * MeSH
• pohyby očí MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• sakadické oční pohyby MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder with varying symptomatology depending on the age of onset. The diagnosis of NP-C is challenging due to heterogeneous nonspecific clinical presentation of the disease. NP-C Suspicion Index (SI) was developed to aid screening and identification of patients with suspicion of NP-C for further clinical evaluation. Here we assess the performance of five NP-C SI models to identify patients with NP-C compared with clinical practice to determine the best SI model for identification of each clinical form of NP-C by age. METHODS: This was a post hoc analysis of a retrospective chart review of patient data collected from five expert NP-C centers. The study assessed the proportion of patients with NP-C who could have been identified using the Original SI, Refined SI, 2/7 SI, 2/3 SI, and Early-Onset SI and evaluated the performance of each SI against clinical practice. A score above a threshold of 70 points for the Original SI, 40 points for the Refined SI, 6 points for the Early-Onset SI, and 2 points for the 2/7 and 2/3 SIs represented identification of NP-C. RESULTS: The study included 63 patients, and of these, 23.8% had a family history of NP-C. Of the available SI tools, the Refined SI performed well in identifying patients with NP-C across all age groups (77.8% infantile, 100% juvenile and 100% adult groups), and earlier identification than clinical diagnosis would have been possible in 50.0% of infantile, 72.7% of juvenile and 87.0% of adult patients. Patients who were not detected by the Refined SI prior to clinical diagnosis mainly presented with delayed developmental milestones, visceral manifestations, neurologic hypotonia, clumsiness, ataxia, vertical supranuclear gaze palsy, parent or siblings with NP-C, dysarthria/dysphagia and psychotic symptoms. CONCLUSION: This study demonstrated the applicability of various SI models for screening and identification of patients with NP-C for further clinical evaluation. Although NP-C is rare and the patient population is limited, this study was conducted in a real-world setting and confirms SI models as useful screening tools that facilitate identification of patients with NP-C earlier in their disease course.

• MeSH
• hodnocení rizik MeSH
• lidé MeSH
• Niemannova-Pickova nemoc typu C diagnóza   MeSH
• novorozenecká žloutenka diagnóza   MeSH
• psychotické poruchy diagnóza   MeSH
• retrospektivní studie MeSH
• věkové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology. The signs and symptoms of NP-C vary with age at disease onset, and available therapies are directed at alleviating symptoms and stabilizing disease progression. We report the characteristics and factors related to disease progression, and analyze the effect of miglustat treatment on disease progression and patient survival using NP-C disability scales. METHODS: This retrospective, observational chart review included patients with NP-C from five expert NP-C centers. Patient disability scores were recorded using three published NP-C disability scales, and a unified disability scale was developed to allow comparison of data from each scale. Disease progression was represented by scores on the unified NP-C disability scale. Patients were stratified as infantile (< 4 years), juvenile (≥ 4 - < 16 years), and adult (≥ 16 years) based on age at diagnosis, and treated ≥1 year and non-treated/treated < 1 year based on the duration of miglustat treatment. RESULTS: The analysis included 63 patients; the majority (61.9%) were on miglustat therapy for ≥1 year. Ataxia and clumsiness/frequent fall were the most common neurologic symptoms across age groups, whereas, hypotonia and delayed developmental milestones were specific to infantile patients. In both infantile and juvenile patients, visceral signs preceded diagnosis and neurologic signs were noted at or shortly after diagnosis. Adult patients presented with a range of visceral, neurologic, and psychiatric signs in years preceding diagnosis. Patients on miglustat therapy for ≥1 year had a lower mean annual disease progression compared with those untreated/treated < 1 year (1.32 vs 3.54 points/year). A significant reduction in annual disease progression in infantile patients, and a trend towards reduced disease progression in juvenile patients after ≥1 year of miglustat treatment, translated into higher age at last contact or death in these groups. CONCLUSIONS: The type and onset of symptoms varied across age groups and were consistent with descriptions of NP-C within the literature. Miglustat treatment was associated with a reduced rate of disability score worsening in infantile and juvenile patients, both in agreement with increased age at last contact.

• MeSH
• 1-deoxynojirimycin analogy a deriváty   terapeutické užití   MeSH
• dítě MeSH
• lidé MeSH
• lineární modely MeSH
• mladiství MeSH
• Niemannova-Pickova nemoc typu C farmakoterapie   patologie   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

BACKGROUND: Niemann-Pick disease Type C (NP-C) is difficult to diagnose due to heterogeneous and nonspecific clinical presentation. The NP-C Suspicion Index (SI) was developed to identify patients with a high likelihood of NP-C; however, it was less reliable in patients aged <4 years. METHODS: An early-onset NP-C SI was constructed following retrospective chart review of symptom presentation in 200 patients from nine centres comprised of 106 NP-C cases, 31 non-cases and 63 controls. Statistical analyses defined strength of association between symptoms and a diagnosis of NP-C and assigned risk prediction scores to each symptom. RESULTS: Visceral symptoms were amongst the strongest predictors. Except for gelastic cataplexy and vertical supranuclear gaze palsy, central nervous system symptoms were not discriminatory in this population. Performance of the early-onset NP-C SI was superior versus the original NP-C SI in patients aged ≤4 years. CONCLUSIONS: The early-onset NP-C SI can help physicians, especially those with limited knowledge of NP-C, to identify patients aged ≤4 years who warrant further investigation for NP-C.

• MeSH
• hodnocení rizik MeSH
• kojenec MeSH
• lidé MeSH
• logistické modely MeSH
• metody pro podporu rozhodování * MeSH
• Niemannova-Pickova nemoc typu C diagnóza   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• senzitivita a specificita MeSH
• studie případů a kontrol MeSH
• ukazatele zdravotního stavu * MeSH
• věkové faktory MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH