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(1) Background: Sustained axonal degeneration may play a critical role in prolonged disorder of consciousness (DOCs) pathophysiology. We evaluated levels of neurofilament light chain (NFL), an axonal injury marker, in patients with unresponsive wakefulness syndrome (UWS) and in the minimally conscious state (MCS) after traumatic brain injury (TBI) and hypoxic-ischemic brain injury (HIBI). (2) Methods: This prospective multicenter blinded study involved 70 patients with prolonged DOC and 70 sex-/age-matched healthy controls. Serum NFL levels were evaluated at 1-3 and 6 months post-injury and compared with those of controls. NFL levels were compared by DOC severity (UWS vs. MCS) and etiology (TBI vs. HIBI). (3) Results: Patients' serum NFL levels were significantly higher than those of controls at 1-3 and 6 months post-injury (medians, 1729 and 426 vs. 90 pg/mL; both p < 0.0001). NFL levels were higher in patients with UWS than in those in MCS at 1-3 months post-injury ( p = 0.008) and in patients with HIBI than in those with TBI at 6 months post-injury ( p = 0.037). (4) Conclusions: Patients with prolonged DOC present sustained axonal degeneration that is affected differently over time by brain injury severity and etiology.

Cyclophosphamide (CTX) is an alkylating agent related to nitrogen mustards whose anti-inflammatory and immunosuppressive effects have been utilised to treat selected cases of multiple sclerosis with a progressive and worsening course. To halt the progression of disease in patients refractory to disease modifying drugs CTX has been given, and several open-label studies have recently shown clinical benefits. In a previous study we demonstrated the effectiveness of a combination of IV monthly pulses of CTX and interferon beta (IFN-beta) in 10 patients with "rapidly transitional" form of multiple sclerosis characterised by severe and frequent attacks and rapid progression of disability. The present study reports the clinical and MRI follow-up 36 months after the discontinuation of CTX showing the maintenance of the results obtained in relapse rate (p<0.001), EDSS (p<0.001), T2 MRI total lesion load (p<0.001) and T2 lesions number (p<0.001) compared to the pre-treatment period. These encouraging findings and the absence of significant recorded side effects affirm that the association of CTX plus interferon-beta is amenable, safe and can be recommended in rapidly worsening MS patients.

It is well known that neurorehabilitation can reduce disability or improve handicap of people with multiple sclerosis (MS). The aim of this study was to evaluate the effectiveness of a short period (6 weeks) of a tailored, individualised outpatient rehabilitation program in people with progressive MS. A randomised-controlled trial was undertaken in patients with primary and secondary progressive MS referred to the Centro Sclerosi Multipla of Catania. One hundred and eleven patients were assessed at baseline and at 12 weeks with validated measures of disability (Functional Independence Measure (FIM)) and impairment (Expanded Disability Status Scale (EDSS) and Functional Systems Scale). Of the 111, 58 were randomly assigned to the treatment group and 53 to the control group. All patients had been previously trained in a home exercise program. Both groups were well matched for age, sex, disease duration and severity, disability and quality of life (Short Form-36). At the end of 6 weeks patients allocated to the rehabilitation treatment group showed significant improvement in their level of disability compared with the control group,while the level of impairment did not change. Thirty-two patients of the treatment group and four of the control group improved on the FIM by two or more steps at 12 weeks (p<0.0001). An improvement by 1 EDSS step occurred in only two patients of the treatment group and in one patient of the control group. Benefits were maintained for a further six weeks. This study demonstrates that a short outpatient rehabilitation treatment improves disability of MS patients, without changing their impairment and confirms the effectiveness of rehabilitation in people with MS.