Infusion-related reactions during Natalizumab treatment: Do we still need a post-infusion observation period?

BACKGROUND: Natalizumab (NTZ) is a humanized monoclonal antibody used in the treatment of relapsing remitting multiple sclerosis. Although NTZ is usually well-tolerated, infusion-related reactions (IRRs) may occur, and the patients have to be monitored during the infusion and for one hour afterwards. OBJECTIVE: To identify frequency and severity of IRRs during NTZ infusions and one-hour post-infusion observation period in a clinical practice setting. METHODS: Multicenter, observational study involving three Swiss (Lugano, St. Gallen and Luzern) and two Italian (Milano and Napoli) tertiary MS centers. Predisposing factors to IRRs were investigated using multivariate Cox regression models. RESULTS: A total of 11'133 infusions received by 302 MS patients were analyzed (68.9% females, median age 33.6 years, median EDSS 2.5). IRRs occurred in 24 (8%) patients during NTZ infusions and in 7 (2%) during one-hour post-infusion. Only 8 patients needed pharmacological treatment, of whom 7 during NTZ infusion. Age, sex and history of allergies were not associated with risks for IRR. The frequency of post infusion IRRs after the fifth cycle was low compared to that during the first four infusions (0.83% vs 0.06%). CONCLUSION: In our cohort, NTZ associated IRR mainly occurred during the infusion period compared to the one-hour observational period. Also, the first IRR exclusively occurred within the first 4 NTZ administrations. However, further multi-center studies with a larger sample size are needed to capture rare and serious events that could emerge during the observational period and to make clinical recommendations.

Focal neuromyotonia: do I love you?

We present a rare case of focal neuromyotonia in a 73-year-old woman with a follow up of 5 years. The clinical picture showed a fixed contraction of the 3rd and 4th finger of the left hand. Similar to other published cases, our patient suffered from COPD and was treated with beta-2-sympathomimetics. This clinical picture shows a rare but rather salient differential diagnosis of Dupuytren's contracture. EMG of the affected muscles may yield a diagnosis and prevent the patient from a long and ineffective treatment "odyssey".

Intravenous thrombolysis in patients with stroke attributable to small artery occlusion.

BACKGROUND: Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Recent observations raised concern that IVT might cause harm in patients with strokes attributable to small artery occlusion (SAO). OBJECTIVE: The safety of IVT in SAO-patients is addressed in this study. METHODS: We used the Swiss IVT databank to compare outcome and complications of IVT-treated SAO-patients with IVT-treated patients with other etiologies (non-SAO-patients). Main outcome and complication measures were independence (modified Rankin scale 0.8). Fatal ICH occurred in 3.3% of the non-SAO-patients but none amongst SAO-patients. Ischaemic stroke within 3 months after IVT reoccurred in 1.5% of SAO-patients and in 2.3% of non-SAO-patients (P = 0.68). CONCLUSION: IVT-treated SAO-patients died less often and reached independence more often than IVT-treated non-SAO-patients. However, the variable 'SAO' was a dependent rather than an independent outcome predictor. The absence of an excess in ICH indicates that IVT seems not to be harmful in SAO-patients.

Increased collateral sprouting of primary afferents in the myelin-free spinal cord.

After partial lesions, uninjured nerve fibers have been shown to sprout and expand their connections within the CNS of adult mammals. The extent of this anatomical plasticity in adults is rather limited in comparison to embryonic or neonatal animals. Factors that might limit sprouting of nerve fibers and suppress anatomical plasticity in the CNS include myelin-associated neurite growth inhibitory molecules present in the CNS of adult mammals. To examine further the role of these neurite growth inhibitors, we have studied the ability of primary afferent fibers to sprout in the absence of myelin within a partially deafferented spinal cord. Myelination was suppressed in the lower thoracic and lumbar spinal cord of rats using neonatal x-irradiation. Dorsal roots of lumbar segments L2-L4 were cut in myelin-free and normal spinal cords of 8- or 15-d-old rats. Sprouting of primary afferents was measured after 20 d using thiamine monophosphatase (TMP) histochemistry. TMP is a specific marker enzyme for small-diameter primary afferents that terminate in the substantia gelatinosa (lamina II) of the spinal cord. When compared to the control groups, collateral sprouting of TMP-positive afferents was significantly enhanced in the myelin-free spinal cords: in animals deafferented at postnatal day P8, the average volume occupied by sprouting fibers in the upper dorsal horn was 0.103 mm3 +/- 0.008 (mean +/- SEM) in myelin-free spinal cords and 0.044 mm3 +/- 0.011 in control spinal cords. In spinal cords deafferented at P15, this difference was even larger, with 0.106 mm3 +/- 0.010 in the absence of myelin and 0.031 mm3 +/- 0.010 in controls. Our results indicate that myelin and its associated neurite growth inhibitors restrict collateral sprouting. These data provide further evidence that CNS myelin and its associated neurite growth inhibitors are involved in the regulation of anatomical plasticity in the normal CNS.