Activation of the p38MAPK cascade is associated with upregulation of TNF alpha receptors in the spinal motor neurons of mouse models of familial ALS.

Phosphorylated p38 mitogen-activated protein kinase (p38MAPK), but not activated c-jun-N-terminal kinase (JNK), increases in the motor neurons of transgenic mice overexpressing ALS-linked SOD1 mutants at different stages of the disease. This effect is associated with a selective increase of phosphorylated MKK3-6, MKK4 and ASK1 and a concomitant upregulation of the TNFalpha receptors (TNFR1 and TNFR2), but not IL1beta and Fas receptors. Activation of both p38 MAPK and JNK occurs in the activated microglial cells of SOD1 mutant mice at the advanced stage of the disease; however, this effect is not accompanied by the concomitant activation of the upstream kinases ASK1 and MKK3,4,6, while both …

REM sleep behavior disorder and periodic leg movements during sleep in ALS

Objective To assess sleep characteristics and the occurrence of abnormal muscle activity during sleep, such as REM sleep without atonia (RSWA), REM sleep behavior disorder (RBD), and periodic leg movements during sleep (PLMS), in patients with amyotrophic lateral sclerosis (ALS). Methods A total of 41 patients with ALS and 26 healthy subjects were submitted to clinical interview and overnight video-polysomnography. Results A total of 22 patients with ALS (53.6%) reported poor sleep quality. Polysomnographic studies showed that patients with ALS had reduced total sleep time, increased wakefulness after sleep onset, shortened REM and slow-wave sleep, and decreased sleep efficiency, compared t…

Pulmonary function deterioration and chronic hypoventilation in Amyotrophic Lateral Sclerosis

EFFECTS OF SHIFT WORK ON CARDIOVASCULAR ACTIVITY, SERUM CORTISOL AND WHITE BLOOD CELLS COUNT IN A GROUP OF ITALIAN FISHERMEN

We analyzed the effects of working activity and working shifts on the circadian rhythmicity and circadian phase relations of serum cortisol level, white blood cells count, resting heart rate and systolic/diastolic blood pressure in a group of italian fishermen. We observed a shift-induced displacement of cortisol secretion and a modification in leukocyte count. Moreover, systolic/diastolic blood pressure and resting heart rate were markedly influenced by the night shift, whereas no appreciable changes were observed after the morning and afternoon shifts, compared to pre-working values. These data suggest that the human circadian system is greatly influenced by shift work, and serum cortisol…

MARITAL STATUS IS A PROGNOSTIC FACTOR IN AMYOTROPHIC LATERAL SCLEROSIS

Background and objectives Several variables have been linked to a shorter survival in patients with amyotrophic lateral sclerosis (ALS), for example, female sex, older age, site of disease onset, rapid disease progression, and a relatively short diagnostic delay. With regard to marital status, previous studies suggested that living with a partner might be associated to a longer survival and a higher likelihood to proceed to tracheostomy. Therefore, to further strengthen this hypothesis, we investigated the role of marital status as a prognostic variable in a cohort of ALS patients. Methods We performed a retrospective analysis on 501 consecutive ALS patients for which a complete disease's n…

Noninvasive positive-pressure ventilation in ALS: predictors of tolerance and survival.

Objective: To identify factors associated with tolerance and survival after noninvasive positive-pressure ventilation (NIPPV) and to investigate the influence of NIPPV on lung function in patients with ALS. Methods: NIPPV was offered to 71 patients with ALS in accordance with currently published guidelines. Effects of NIPPV on lung function and factors influencing tolerance and survival after NIPPV were studied. Results: Forty-four patients (61.9%; 95% CI: 50.6 to 73.2) tolerated NIPPV (NIPPV use >= 4 h/day) and 27 (38.1%; 95% CI: 26.8 to 49.4) were intolerant (NIPPV use = 4 h/day) and to the modifications of forced vital capacity decline after treatment initiation. The severity of bulbar i…

Autosomal dominant hereditary spastic paraplegia: report of a large italian family with R581X spastin mutation

We describe a large kindred with a typical pure form of autosomal dominant hereditary spastic paraplegia (ADHSP). On the basis of maximum LOD score of 1.94 at theta (max)=0 with marker D2S367, we obtained suggestive evidence for linkage of ADHSP to SPG4 locus. Denaturing high-performance liquid chromatography (DHPLC) and direct sequence analysis allowed us to identify a nonsense mutation (1741* C > T) in exon 17 of the Spastin gene. This transition, carried by all the affected family members and two apparently healthy individuals, lead to truncation of the last 36 amino acids in the C-terminus of the protein. These results confirm the existence of mutation in the SPG4 gene with a reduced pe…

POST-TRAUMATIC STRESS DISORDER: A FREQUENT WORK-RELATED ILLNESS

Post-traumatic stress disorder (PTSD) is an anxiety disorder that results from exposure to a traumatic event, and is characterized by hypermnesia of the traumatic event with frequent re-experiencing of the tragic occurrence, hyperarousal, and avoidance behaviour. Depression, anxiety, sleep dysfunction and substance abuse are also commonly reported. PTSD is highly prevalent both in the general population and in certain occupations that are particularly exposed to life-threatening situations, physically and psychological demanding activities, and physical assault, such as rescue workers, firefighters and paramedics. Recent advances in the comprehension of the epidemiology, physiopathology and…

How specific are the pontine MRI hyperintensities (the cross sign)?

Fatigue, sleep, and nocturnal complaints in patients with amyotrophic lateral sclerosis

Background and purpose: Fatigue is a common symptom in amyotrophic lateral sclerosis (ALS). Although sleep disturbances are a candidate factor that may interfere with fatigue in patients with ALS, the role of sleep-related abnormalities in determining fatigue in ALS is unknown. Objective: To evaluate the frequency and determinants of fatigue in a group of 91 consecutive patients with ALS, with special attention to the relationship between fatigue and sleep problems. Methods: Measures included the Fatigue Severity Scale (FSS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), ALS Functional Rating ScaleRevised (ALSFRS-R), and Beck Depression Inventory (BDI). Results: The…

Response to the letter to the Editor: Comments on marital status is a prognostic factor in amyotrophic lateral sclerosis. Safiri S et al

Inter- and intracellular signaling in amyotrophic lateral sclerosis: role of p38 mitogen-activated protein kinase.

The pathogenetic processes underlying the selective motor neuron degeneration in amyotrophic lateral sclerosis (ALS) are complex and still not completely understood even in the cases of inherited disease caused by mutations in the Cu/Zn superoxide dismutase-dependent (SOD1) gene. Recent evidence supports the view that ALS is not a cell-autonomous disease and that glial-neuron cross-talk, throughout cytokines and other toxic factors like the nitric oxide and superoxide, is a crucial determinant for the induction of motor neuron death. This cell-cell interaction may determine the progression of the disease through processes that are likely independent of the initial trigger and that may conve…