Late-Onset N-Acetylglutamate Synthase Deficiency: Report of a Paradigmatic Adult Case Presenting with Headaches and Review of the Literature.

N-acetylglutamate synthase deficiency (NAGSD) is an extremely rare urea cycle disorder (UCD) with few adult cases so far described. Diagnosis of late-onset presentations is difficult and delayed treatment may increase the risk of severe hyperammonemia. We describe a 52-year-old woman with recurrent headaches who experienced an acute onset of NAGSD. As very few papers focus on headaches in UCDs, we also report a literature review of types and pathophysiologic mechanisms of UCD-related headaches. In our case, headaches had been present since puberty (3-4 days a week) and were often accompanied by nausea, vomiting, or behavioural changes. Despite three previous episodes of altered consciousness, ammonia was measured for the first time at 52 years and levels were increased. Identification of the new homozygous c.344C>T (p.Ala115Val) NAGS variant allowed the definite diagnosis of NAGSD. Bioinformatic analysis suggested that an order/disorder alteration of the mutated form could affect the arginine-binding site, resulting in poor enzyme activation and late-onset presentation. After optimized treatment for NAGSD, ammonia and amino acid levels were constantly normal and prevented other headache bouts. The manuscript underlies that headache may be the presenting symptom of UCDs and provides clues for the rapid diagnosis and treatment of late-onset NAGSD.

The validation of an Italian version of the Freezing of Gait Questionnaire.

Freezing of gait (FOG) is a common and disabling symptom in Parkinson's disease (PD) and its staging is complex because of its episodic nature. Patient-reported assessments are essential in evaluating this disabling symptom. The Freezing of Gait Questionnaire (FOG-Q) is considered a valid and reliable tool for the assessment of FOG severity. The aim of our study was to validate the Italian version of FOG-Q and to investigate for its association with several clinical aspects of PD. Fifty-one PD patients were administered the FOG-Q and the timed up and go test. Moreover, patients were evaluated for the unified PD rating scale (UPDRS), the Hoehn and Yahr Scale (H&Y) and the falls-efficacy scale [FES(S)]. Mean (SD) FOG-Q item scores ranged between 1.5 and 2.7 (1.0-1.4); corrected item-total correlations ranged between 0.63 and 0.86. The total FOG-Q score ranged between 0 and 24, with a mean + SD of 12.6 (6.2) and a median (q1-q3) of 12 (9-17). Reliability was 0.91. FOG-Q correlated with H&Y (0.36, p = 0.0091), UPDRS part III (rS = 0.27, p = 0.054), PD duration (rS = 0.35, p < 0.01), FES(S) (rS = 0.58, p < 0.001) and the timed up and go test (rS = 0.51, p = 0.001). Non-significant positive correlations were observed for dyskinesia and motor fluctuations. Our study validates the Italian version of the FOG-Q, in that it results being a reliable instrument for assessing FOG in PD patients.

Interatrial Shunting Through an Asymptomatic Patent Foramen Ovale in Thoracic Surgery.

BACKGROUND: Patent foramen ovale (PFO) is present in as many as 25% of the general population and is considered an irrelevant condition in healthy subjects. Here, we sought to determine an association between an asymptomatic PFO at baseline and postoperative short-term adverse events in patients undergoing major pulmonary resection for lung cancer. In addition, we evaluated for the rate of PFO after pulmonary resections. METHODS: This prospective, observational study assessed patients by transcranial Doppler with contrast at baseline and discharge. To confirm interatrial shunting, patients with positive transcranial Doppler at baseline also underwent contrast transthoracic echocardiography. Multivariate logistic regression models were adopted to investigate for independent factors that could have been associated with complications. Backward stepwise procedure was used for model selection. RESULTS: Median age was 67.7 ± 9.2 years (range, 36 to 86), and 67% were men. Overall, 18 patients underwent pneumonectomy, 11 bilobectomy, and 118 lobectomy; 54% underwent right-sided procedure and 46%, left-sided. One perioperative death was recorded, and 34 patients had one or more cardiopulmonary complications. At baseline, PFO was positive in 25% (37 of 147) and negative in 75% (110 of 147); of the latter, 11% were positive at discharge. Detection of PFO at baseline, on multivariate analysis, was significantly associated with a risk of postoperative complications (odds ratio 2.5; 95% confidence interval: 1.1 to 5.8). Specifically, we observed a significant association between atrial fibrillation and positive PFO at baseline (odds ratio 3.5; 95% confidence interval: 1.4 to 9.0). CONCLUSIONS: Preoperative asymptomatic PFO was independently associated with postoperative adverse events. Moreover, 11% of patients who had negative transcranial Doppler studies at baseline had asymptomatic PFOs at discharge. Larger prospective studies are needed to further investigate for a prognostic impact of PFO in thoracic surgery.