Characteristic eye movements in ataxia-telangiectasia-like disorder: An explanatory hypothesis

Objective: To investigate cerebellar dysfunctions and quantitatively characterize specific oculomotor changes in ataxia-telangiectasia-like disorder (ATLD), a rare autosomal recessive disease caused by mutations in the MRE11 gene. Additionally, to further elucidate the pathophysiology of cerebellar damage in the ataxia-telangiectasia (AT) spectrum disorders. Methods: Saccade dynamics, metrics, and visual fixation deficits were investigated in two Italian adult siblings with genetically confirmed ATLD. Visually guided saccades were compared with those of 40 healthy subjects. Steady fixation was tested in primary and eccentric positions. Quantitative characterization of saccade parameters, saccadic intrusions (SI), and nystagmus was performed. Results: Patients showed abnormally hypermetric and fast horizontal saccades to the left and greater inaccuracy than healthy subjects in all saccadic eye movements. Eye movement abnormalities included slow eye movements that preceded the initial saccade. Horizontal and vertical spontaneous jerk nystagmus, gaze-evoked, and rebound nystagmus were evident. Fixation was interrupted by large square-wave jerk SI and macrosaccadic oscillations. Conclusion: Slow eye movements accompanying saccades, SI, and cerebellar nystagmus are frequently seen in AT patients, additionally our ATLD patients showed the presence of fast and hypermetric saccades suggesting damage of granule cell-parallel fiber-Purkinje cell synapses of the cerebellar vermis. A dual pathogenetic mechanism involving neurodevelopmental and neurodegenerative changes is hypothesized to explain the peculiar phenotype of this disease

La "compliance" alle GMP nella produzione di scaffolds fabbricati con il sistema PAM: analisi del processo di produzione, applicando un approccio basato sul rischio

Nel presente lavoro di tesi si vuole pianificare un programma di convalida del processo di produzione di Scaffolds di Alginato di Sodio cross-linked, fabbricati utilizzando il sistema PAM, Pressure-Activated Microsyringe, al fine di contribuire ad una crescita complessiva della qualità del prodotto. Si pianifica un programma di convalida del processo di produzione condotto in conformità con le Good Manufacturing Practice, supportato da un'analisi razionale e sistematica delle criticità del processo di produzione, analisi sviluppata con la metodologia dell’Analisi del Rischio. Si realizza la documentazione specifica per definire il prodotto e il processo di produzione in esame necessaria per operare in ambito GMP. Si realizza un documento efficace ed efficiente che ha la funzione di guida per la futura implementazione di un sistema di controlli per il monitoraggio del processo di produzione di Scaffolds di Alginato di Sodio cross-linked. Si individuano le azioni da intraprendere per la qualificazione del sistema di produzione e la convalida del processo di produzione. Quindi, si pianifica un programma documentato per garantire, sistematicamente e con elevato grado di sicurezza, l’ottenimento di un prodotto con specifiche predeterminate, raggiungendo all’obbiettivo fissato

Spike removal through multiscale wavelet and entropy analysis of ocular motor noise: a case study in patients with cerebellar disease.

Wavelet decomposition of ocular motor signals was investigated with a view to its use for noise analysis and filtering. Ocular motor noise may be physiological, depending on brain activities, or experimental, depending on the eye recording machine, head movements and blinks. Experimental noise, such as spikes, must be removed, preserving noise due to neuro-physiological activities. The proposed method uses wavelet multiscale decomposition to remove spikes and optimizes the procedure by means of the covariance of the eye signals. To measure the noise on eye motor control, we used the wavelet entropy. The method was tested on patients with cerebellar disorders and healthy subjects. A significant difference in wavelet entropy was observed, indicating this quantity as a valuable measure of physiological motor noise

Anti-Saccades in Cerebellar Ataxias Reveal a Contribution of the Cerebellum in Executive Functions

ObjectiveIncreasing evidence suggests a cerebellar contribution to modulate cognitive aspects of motor behavior and executive functions. Supporting findings come from studies on patients with neurodegenerative diseases, in which however, given the extent of the disease, the specific role of the cerebellum, could not be clearly isolated. Anti-saccades are considered a sensitive tool to test executive functions. The anti-saccade underlying neural network, consisting of different cortical areas and their downstream connections including the lateral cerebellum, has been largely clarified. To separate the role of the cerebellum with respect to other cortical structures in executive control, we compared the anti-saccade performances in two distinct cohorts of patients with cerebellar disorders (with and without cerebral cortical involvement).MethodsEye movements during the execution of anti-saccades were recorded in 12 patients with spinocerebellar ataxia type 2 (a cortical-subcortical neurodegenerative disease), 10 patients with late onset cerebellar ataxia (an isolated cerebellar atrophy), and 34 matched controls.ResultsIn the anti-saccade task, besides dynamic changes already demonstrated in the pro-saccades of these patients, we found in both groups of cerebellar patients prolonged latency with larger variability than normal and increased directional error rate. Errors, however, were corrected by cerebellar patients as frequently as normal. No significant differences were found in patients with and without cortical involvement.ConclusionOur results indicate, in a large cohort of cerebellar patients, that the cerebellum plays a critical role in the regulation of executive motor control not only, as well known, by controlling the end of a movement, but also modulating its initiation and reducing reflexive responses that would perturb voluntary actions