Our objective was to assess the effects of acetyl-L-carnitine (ALC) with riluzole on disability and mortality of amyotrophic lateral sclerosis (ALS). Definite/probable ALS patients, 40-70 years of age, duration 6-24 months, self-sufficient (i.e. able to swallow, cut food/handle utensils, and walk), and with forced vital capacity (FVC) > 80% entered a pilot double-blind, placebo-controlled, parallel group trial and were followed for 48 weeks. ALC or placebo 3 g/day was added to riluzole 100 mg/day. Primary endpoint: number of patients no longer self-sufficient. Secondary endpoints: changes in ALSFRS-R, MRC, FVC and McGill Quality of Life (QoL) scores. Analysis was made in the intention-to-treat (ITT) and per-protocol (PP) population, completers and completers/compliers (i.e. taking > 75% of study drug). Forty-two patients received ALC and 40 placebo. In the ITT population, 34 (80.9%) patients receiving ALC and 39 (97.5%) receiving placebo became non-self-sufficient (p = 0.0296). In the PP analysis, percentages were 84.4 and 100.0% (p = 0.0538), respectively. Mean ALSFRS-R scores at 48 weeks were 33.6 (SD 10.4) and 27.6 (9.9) (p = 0.0388), respectively, and mean FVC scores 90.3 (32.6) and 58.6 (31.2) (p = 0.0158), respectively. Median survival was 45 months (ALC) and 22 months (placebo) (p = 0.0176). MRC, QoL and adverse events were similar. In conclusion, ALC may be effective, well-tolerated and safe in ALS. A pivotal phase III trial is needed.

We report the case of a patient with hereditary ceruloplasmin deficiency due to a novel gene mutation in ceruloplasmin gene (CP), treated with fresh frozen plasma (FFP) and iron chelation therapy. A 59-year-old man with a past history of diabetes was admitted to our department due to progressive gait difficulties and cognitive impairment. Neurological examination revealed a moderate cognitive decline, with mild extrapyramidal symptoms, ataxia, and myoclonus. Brain T2-weighted MR imaging showed bilateral basal ganglia hypointensity with diffuse iron deposition. Increased serum ferritin, low serum copper concentration, undetectable ceruloplasmin, and normal urinary copper excretion were found. The genetic analysis of the CP (OMIM #604290) reported compound heterozygosity for two mutations, namely c.848G > A and c.2689_2690delCT. Treatment with FFP (500 mL i.v./once a week) and administration of iron chelator (Deferoxamine 1000 mg i.v/die for 5 days, followed by Deferiprone 500 mg/die per os) were undertaken. At the 6-month follow-up, clinical improvement of gait instability, trunk ataxia, and myoclonus was observed; brain MRI scan showed no further progression of basal ganglia T2 hypointensity. This case report suggests that the early initiation of combined treatment with FFP and iron chelation may be useful to reduce the accumulation of iron in the central nervous system and to improve the neurological symptoms.

A 48 year old woman complained of mild weakness and paresthesias of the left limbs, followed 15 days later by episodes of paroxysmal dystonia of the left limbs occurring several times daily over 10 day period. Magnetic resonance imaging (MRI) of head and neck revealed a small area of altered signal in the T2-weighted sequences in the left posterolateral quadrant of the cord at the second cervical vertebra. An MRI scan 18 months later showed no lesion. This is the second case of paroxysmal dystonia with a single MRI lesion in the cervical region on record.

The Italian Oncology Group for Clinical Research tested two experimental chemotherapy strategies in an attempt to improve the results achievable with conventional chemotherapy in metastatic breast cancer. One hundred sixty-two patients were randomly allocated as follows: (a) to the conventional cyclophosphamide, methotrexate, 5-fluorouracil chemotherapy regimen (CMF); (b) to a rotational crossing program (ROT-CROSS); or (c) to a sequential intensification program (SEQ-INT). The same single agents (C, M, F, cisplatin, etoposide, and doxorubicin) were administered in both experimental arms, but following a different policy. The SEQ-INT program induced a significantly higher complete response (32% vs. 6%, p = 0.0006) and objective response rate (72% vs. 42%, p = 0.0047) than CMF did. There were no differences in survival between CMF and either experimental arm. A number of side effects were significantly more with both experimental chemotherapies than with CMF, but the treatments were generally tolerable. Although some caution is required when interpreting a significant advantage found between an entire chemotherapeutic strategy and a single conventional combination, this study documents the potential therapeutic advantage of administering different sequential chemotherapies, and changing each at the time of maximum result without waiting for a progression. The impressive cytoreductive effects achievable with this policy (SEQ-INT) in metastatic disease merit further investigation in the adjuvant setting.