Early co-occurrence of a neurologic-psychiatric disease pattern in Niemann-Pick type C disease: a retrospective Swiss cohort study

BackgroundNiemann-Pick disease type C (NP-C) is a rare autosomal recessive disorder of lysosomal cholesterol transport. The objective of this retrospective cohort study was to critically analyze the onset and time course of symptoms, and the clinical diagnostic work-up in the Swiss NP-C cohort.MethodsClinical, biochemical and genetic data were assessed for 14 patients derived from 9 families diagnosed with NP-C between 1994 and 2013. We retrospectively evaluated diagnostic delays and period prevalence rates for neurological, psychiatric and visceral symptoms associated with NP-C disease. The NP-C suspicion index was calculated for the time of neurological disease onset and the time of diagnosis.ResultsThe shortest median diagnostic delay was noted for vertical supranuclear gaze palsy (2y). Ataxia, dysarthria, dysphagia, spasticity, cataplexy, seizures and cognitive decline displayed similar median diagnostic delays (4¿5y). The longest median diagnostic delay was associated with hepatosplenomegaly (15y). Highest period prevalence rates were noted for ataxia, dysarthria, vertical supranuclear gaze palsy and cognitive decline. The NP-C suspicion index revealed a median score of 81 points in nine patients at the time of neurological disease onset which is highly suspicious for NP-C disease. At the time of diagnosis, the score increased to 206 points.ConclusionA neurologic-psychiatric disease pattern represents the most characteristic clinical manifestation of NP-C and occurs early in the disease course. Visceral manifestation such as isolated hepatosplenomegaly often fails recognition and thus highlights the importance of a work-up for lysosomal storage disorders. The NP-C suspicion index emphasizes the importance of a multisystem evaluation, but seems to be weak in monosymptomatic and infantile NP-C patients.

Reading performance is not affected by a prism induced increase of horizontal and vertical vergence demand

PURPOSE Dyslexia is the most common developmental reading disorder that affects language skills. Latent strabismus (heterophoria) has been suspected to be causally involved. Even though phoria correction in dyslexic children is commonly applied, the evidence in support of a benefit is poor. In order to provide experimental evidence on this issue, we simulated phoria in healthy readers by modifying the vergence tone required to maintain binocular alignment. METHODS Vergence tone was altered with prisms that were placed in front of one eye in 16 healthy subjects to induce exophoria, esophoria, or vertical phoria. Subjects were to read one paragraph for each condition, from which reading speed was determined. Text comprehension was tested with a forced multiple choice test. Eye movements were recorded during reading and subsequently analyzed for saccadic amplitudes, saccades per 10 letters, percentage of regressive (backward) saccades, average fixation duration, first fixation duration on a word, and gaze duration. RESULTS Acute change of horizontal and vertical vergence tone does neither significantly affect reading performance nor reading associated eye movements. CONCLUSION Prisms in healthy subjects fail to induce a significant change of reading performance. This finding is not compatible with a role of phoria in dyslexia. Our results contrast the proposal for correcting small angle heterophorias in dyslexic children.