Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance.

BACKGROUND: A receptor for leptin has been cloned from the choroid plexus, the site of cerebrospinal-fluid (CSF) production and the location of the blood/cerebrospinal-fluid barrier. Thus, this receptor might serve as a transporter for leptin. We have studied leptin concentrations in serum and (CSF). METHODS AND FINDINGS: We demonstrated by radioimmunoassay and western blot the presence of leptin in human CSF. We then measured leptin in CSF and serum in 31 individuals with a wide range of bodyweight. Mean serum leptin was 318% higher in 8 obese (40.2 [SE 8.6] ng/mL) than in 23 lean individuals (9.6 [1.5] ng/mL, p < 0.0005). However, the CSF leptin concentration in obese individuals (0.337 [0.04] ng/mL) was only 30% higher than in lean people (0.259 [0.26] ng/mL, p < 0.1). Consequently, the leptin CSF/serum ratio in lean individuals (0.047 [0.010]) was 4.3-fold higher than that in obese individuals (0.011 [0.002], p < 0.05). The relation between CSF leptin and serum leptin was best described by a logarithmic function (r = 0 x 52, p < 0.01). INTERPRETATION: Our data suggest that leptin enters the brain by a saturable transport system. The capacity of leptin transport is lower in obese individuals, and may provide a mechanism for leptin resistance.

Alterations of motor evoked potentials by thalamotomy.

To evaluate the effect of stereotactic thalamotomy on the function of the corticospinal tract, we studied motor evoked potentials (MEPs) recorded by surface electromyography (EMG) in the left extensor carpi radialis (ECR) and flexor carpi radialis (FCR) with magnetic stimulation of the contralateral motor cortex in a 43-year-old patient with a severe postural and resting tremor of the left hand. The patient was diagnosed eight years previously with left hemiparkinsonism. The tremor was unresponsive to various medications. After thalamotomy the tremor had disappeared, confirmed by EMG studies. MEP latencies at rest were normal and did not change after thalamotomy. Volitional contraction of either ECR or FCR shortened the latency of the corresponding MEP before and after thalamotomy. However, before thalamotomy responses at rest were less well synchronized and followed by EMG silence with subsequent long duration tonic after discharges. Furthermore, during voluntary contraction the responses only slightly enhanced. After surgery MEPs at rest in both muscles were more synchronized and after-discharges had disappeared. Moreover, with volitional contraction of either ECR of FCR, the MEPs enhanced more dramatically. The silent periods (SPs) following the MEP during sustained voluntary contraction were longer after thalamotomy. The consistent MEP latencies suggest that the conduction of the pyramidal tract is unaffected by thalamotomy. The better synchronized responses, the alleviation of after-discharges and the longer SPs in this patient with hemiparkinsonism following thalamotomy suggest an improved sensorimotor integration, which may be the result of a reduced thalamic input onto suprasegmental levels.