Motor function measure: validation of a short form for young children with neuromuscular diseases.

OBJECTIVE: To validate a useful version of the Motor Function Measure (MFM) in children with neuromuscular diseases aged <7 years old. DESIGN: Two prospective cohort studies that documented the MFM completion of children aged between 2 and 7 years old. SETTING: French-speaking rehabilitation departments from France, Belgium, and Switzerland. PARTICIPANTS: Healthy children (n=194) and children with a neuromuscular disease (n=88). INTERVENTIONS: Patients were rated by the MFM either once or twice by trained medical professionals, with a delay between the 2 MFMs ranging between 8 and 30 days. MAIN OUTCOME MEASURE: Intra- and interrater reliability of the MFM. RESULTS: The subtests making up the MFM-32, a scale monitoring severity and progression of motor function in patients with a neuromuscular disease in 3 functional domains, were carried out in healthy children aged 2 to 7 years. Twenty items of the MFM-32 were successfully completed by these children and were used to constitute the MFM-20. Principal component analysis of the MFM-20 confirmed the 3 functional domains. Inter- and intrarater reliability of the 3 subscores and total score were high (intraclass correlation coefficient >.90), and discriminant validity was good. CONCLUSIONS: The MFM-20 can be used as an outcome measure for assessment of motor function in young children with neuromuscular disease.

Carotid Pulse Wave Analysis: Future Direction of Hemodynamic and Cardiovascular Risk Assessment.

Evaluation of the hemodynamic function of the cardiovascular system via measurement of the mechanical properties of the large arteries may provide a substantial improvement over present techniques. Practitioners are familiar with the problem of low reproducibility of conventional sphygmomanometry, which exhibits reasonable accuracy but low precision owing to its marked variability over time and in different circumstances (e.g., the white coat effect). Arterial wall stiffness is a consequence of atherosclerosis developing over time; thus, it has little short-term variability and is thus preferable to be used as a prognostic marker. In particular, arterial stiffness can be evaluated at the carotid artery using noninvasive approaches based on wearable sensor technologies for pulse wave analysis. These enable the assessment of central pressures and pulse waveform parameters that are expected to replace peripheral blood pressure measurement using the inflatable cuff. In this study, we discuss this simple and inexpensive technique, which has been shown to be reliable with the clinical and epidemiological evidence for its use as a biomarker of cardiovascular risk.

Acute effects of 6-hydroxydopamine on dopaminergic neurons of the rat substantia nigra pars compacta in vitro.

6-Hydroxydopamine (6-OHDA) is a neurotoxin which has been implicated in the degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNc) in Parkinson's disease (PD), and is frequently used to produce animal models of the disease. The aim of our study, conducted on midbrain slices obtained from young Wistar rats, was to determine the little known acute effects of this toxin (0.2-2.0 mM; 10-20 min exposure; 34 degrees C) on electrophysiological properties, intracellular Ca2+ levels and dendritic morphology of SNc neurons. Four experimental approaches were used: extracellular recording of firing frequency, whole-cell patch-clamping, ratiometric fura-2 imaging, and cell labeling with lucifer yellow (LY) or dextran-rhodamine. Extracellular recording revealed a concentration-dependent decrease in the tonic, pacemaker-like firing. In whole-cell recordings in voltage-clamp (V(hold) -60 mV), smaller doses (0.2-0.5 mM) induced an outward current (or cell membrane hyperpolarization in current-clamp), which could in some cells be reversed with tolbutamide (blocker of ATP-dependent K+ channels). A higher dose (1.0-2.0 mM) caused rapid reductions of cell membrane capacitance and membrane resistance. Toxin exposure gradually increased the intracellular Ca2+ level, which did not subsequently return to control. The increase in Ca2+ signal was not prevented by depletion of intracellular Ca2+ stores with thapsigargin (10 microM) or cyclopiazonic acid (30 microM), nor by removing extracellular Ca2+. Cell membrane current and Ca2+ responses were not prevented by blocking dopamine transporter (DAT). Cells loaded with LY or dextran-rhodamine showed signs of damage (cell membrane blebbing) in dendrites following toxin exposure (1 mM; 10-20 min). These results demonstrate that the oxidative and metabolic stress induced in SNc neurons by 6-OHDA results in rapid dose-dependent changes of cell membrane properties with morphological evidence of dendritic damage, as well as in disturbance of intracellular Ca2+ homeostasis.

Effects of muscarinic acetylcholine receptor activation on membrane currents and intracellular messengers in medium spiny neurones of the rat striatum.

Acetylcholine, acting through muscarinic receptors, modulates the excitability of striatal medium spiny neurones. However, the underlying membrane conductances and intracellular signalling pathways have not been fully determined. Our aim was to characterize excitatory effects mediated by M1 muscarinic acetylcholine receptors in these neurones using whole-cell patch-clamp recordings in brain slices of postnatal rats. Under voltage-clamp, muscarine evoked an inward current associated with an increase in cell membrane resistance. The current, which reversed at -85 mV, was sensitive to the M1 receptor antagonist pirenzepine. Blocking the potassium conductance attenuated the response and the residual current was further reduced by ruthenium red (50 microm) and reversed at +15 mV. Simultaneous recordings from cholinergic interneurones and medium spiny neurones in conjunction with spike-triggered averaging revealed small unitary excitatory postsynaptic currents in four of 39 cell pairs tested. The muscarine-induced inward current was attenuated by a phospholipase C (PLC) inhibitor, U73122, but not by a protein kinase C inhibitor, chelerythrine, or by the intracellular calcium chelator 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetra-acetic acid, suggesting that the current was associated with PLC in a protein kinase C- and Ca2+ -independent manner. The phosphatidylinositol 4-kinase inhibitor wortmannin (10 microm) reduced the recovery of the inward current, indicating that the recovery process was dependent on the removal of diacylglycerol and/or inositol 1,4,5 triphosphate or resynthesis of phospholipid phosphatidylinositol 4,5-bisphophate. Ratiometric measurement of intracellular calcium after cell loading with fura-2 demonstrated a muscarine-induced increase in calcium signal that originated mainly from intracellular stores. Thus, the cholinergic excitatory effect in striatal medium spiny neurones, which is important in motor disorders associated with altered cholinergic transmission in the striatum such as Parkinson's disease, is mediated through M1 receptors and the PLC-dependent pathway.