Clinical heterogeneity in Italian patients with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rare and devastating neurodegenerative disorder. The majority of cases are sporadic ALS (SALS), with 5-10% being familial ALS (FALS), and are inherited mostly as autosomal dominant. Mutations in Cu/Zn superoxide dismutase (SOD1) and the TAR DNA-binding protein (TARDBP) gene are the most commonly known cause of ALS. We analyzed these genes in 61 Italian ALS patients using high-resolution melting analysis to confirm the role of SOD1 and TARDBP in the physiopathology of ALS. The screenings showed a single mutation in SOD1 (Asp109Tyr) and three in TARBDP (Ala382Thr, Gly295Ser, Gly294Val) in five unrelated ALS patients. This report enlarges the spectrum of clinical phenotypes associated with genetic mutations in SOD1 and TARDBP genes confirming the variability of phenotypes associated with the same mutation and emphasizes the importance of genetic analysis. The different genotype-phenotype correlations suggest the implication of other factors possibly influencing clinical manifestation of the disease, such as an epigenetic or epistatic effect with other genes not yet identified.

Abnormal brain hemodynamic responses during passive orthostatic challenge in panic disorder.

OBJECTIVE: Autonomic dysregulation and cerebral blood flow (CBF) abnormalities have been reported in patients with anxiety disorders and, more recently, in panic disorder. Variations in the middle cerebral artery velocity (measured by transcranial Doppler technique), heart rate, and blood pressure during a tilting-table test were used as nonanxiogenic procedures to explore these abnormalities. METHOD: Mean flow velocity in the right middle cerebral artery, heart rate, and blood pressure were monitored at rest and during a 70 degrees tilting-table test. Three groups of patients were studied: 11 patients (eight women and three men; mean age = 31.1 years, SD = 8.0) with a diagnosis of panic disorder within 6 months of the onset of the disorder, nine asymptomatic patients (two men and seven women; mean age = 35.0, SD = 6.3) with a previous diagnosis of panic disorder who were in full remission of symptoms and had been drug free for at least 6 months, and 10 normal comparison subjects (two men and eight women; mean age = 31.1, SD = 5.2). RESULTS: Both patients with acute panic disorder and patients with remitted panic disorder showed a significant percent reduction of right middle cerebral artery mean flow velocity compared with normal subjects following tilting to the upright position. No significant differences were observed for blood pressure and heart rate. CONCLUSIONS: Patients with panic disorder, both during the acute phase of the illness and after clinical recovery, show an exaggerated drop in CBF during tilting. Since these findings are similar, although attenuated in intensity, to those which are observed in dysautonomic illnesses, one possible interpretation is that of panic disorder as a subclinical form of autonomic dysreactivity.