Brain-derived neurotrophic factor in cerebrospinal fluid of patients with chronic daily headache: relationship with nerve growth factor and glutamate levels

Little has been done to investigate the biochemical basis of chronic daily headache (CDH). Our group has recently demonstrated an increase in the cerebrospinal fluid (CSF) levels of nerve growth factor (NGF) in CDH patients, supporting the involvement of this growth factor in the abnormal processing of head pain in this pathological condition. Other members of the neurotrophin family, especially brain-derived neurotrophic factor (BDNF), have been hypothesized as being involved in the development of chronic head pain in patients affected by CDH, but so far no data are available on this subject. BDNF, NGF and glutamate levels were determined in the CSF of 25 patients affected by CDH with a previous history of migraine. These levels were compared with those of a group of 20 control subjects, for whom the CSF examination and other instrumental investigations excluded diseases of the central and peripheral nervous systems. Significantly higher levels of BDNF, NGF and glutamate were found in CDH patients compared with control subjects (p<0.0001, p<0.0002 and p<0.001, respectively). A significant positive correlation emerged between CSF values of BDNF and those of NGF (r=0.61, p<0.001) and glutamate (r=0.44, p<0.025) in CDH patients. No significant differences were detected in BDNF, NGF and glutamate levels between CDH patients with analgesic overuse and those without. These results support the involvement of BDNF in CDH through the potentiation of glutamatergic transmission involved in the processing of head pain. The significant correlation between BDNF and NGF levels suggests that NGF-mediated up-regulation of BDNF in central sites involved in long-term sensitization plays a key role in persistent head pain in CDH patients. Correspondence to P. Sarchielli     

Microalbuminuria and nerve conduction velocity in type-I diabetics during conventional therapy and during continuous I.V. insulin infusion

Summary The objective of this study was to follow the development of microalbuminuria and nerve conduction velocity under continuous i.v. insulin therapy over a limited period of 4 months. For this purpose, 8 labile type I diabetics were selected (age 33±8 years, duration of diabetes 16±9 years) and treated conventionally with two insulin injections daily over 4 months. Afterwards, the same patients were treated with continuous i.v. insulin infusion and finally again with two injections daily over 4 months each. This procedure allowed each diabetic to serve as his own control. HbA₁, microalbuminuria, nerve conduction velocity and relative refractory period of the ulnar nerve were checked at montly intervals. During the continuous i.v. infusion over 4 months, blood sugar values were significantly lower, glucosuria had disappeared almost completely and the glycosylated hemoglobin had fallen to near normal values. The mean rate of albumin excretion was 16±5 μg/min at rest and 76±26 μg/min during exercise (normal: 3.9±0.4 and 4.8±1.2 μg/min, respectively) and did not change significantly. Nerve conduction velocity in the ulnar nerve rose significantly under i.v. insulin therapy from 47.9±0.6 m/sec to 52±0.6 m/sec. Similarly, the relative refractory period of the same nerve fell significantly from 3.7±0.2 to 1.9±0.1 msec (i.e. to within normal range). It is concluded that functional disturbances of peripheral nerve can regress by improved blood sugar control with continuous i.v. insulin infusion over 4 months. On the other hand, incipient microangiopathy measured as microalbuminuria remains unchanged over the same period of time. If an improvement is at all possible, considerably longer periods of euglycemia are likely to be necessary. Supported by Grant No. 3.964-0.80 from the Swiss National Science Foundation.     

Asystole from tetanic stimulation of the accessory nerve

An asystolic cardiac arrest is reported which occurred at the same time as supramaximal tetanic stimulation over the accessory nerve in order to evoke contractions in the trapezius and sternocleidomastoid muscles. The cause may have been the inadvertent stimulation of one or more of the cranial nerves of the carotid sheath at the base of the skull: the cranial root of the accessory nerve, the vagus, the sino-carotid branch of the glossopharyngeal nerve or the hypoglossal nerve. The most likely culprit, if not the vagus itself, was the cranial root of the accessory nerve which both functionally and anatomically should be seen as an integral part of the vagus. It is suggested that stimulation of any nerve in the carotid sheath should be approached with caution and that a tetanic stimulus to this area might best be avoided.     

神经根变异与特殊型椎间盘突出症

回顾5例由于神经根变异或特殊类型椎间盘突出引起的腰腿痛病人,对其病理及术中处理做了介绍,认为由于神经根的解剖变异,更容易受到椎间盘突出的卡压。手术中如临床症状符合椎间盘突出症,而预定探查间隙未发现突出物,或与临床症状不符者,应根据神经根激惹及松紧程度,扩大探查范围,查明造成疼痛的原因,避免二次手术。     

异体硬脊膜桥接周围神经缺损的实验研究

探讨异体硬脊膜修复周围神经缺损的可行性。方法：采用狗的异体硬脊膜桥接缺损２ｃｍ的狗腓总神经，对照组仅切取２ｃｍ神经而不作处理。在术后不同时间段作大体观察、神经电生理检测、光镜利电镜检查。结果：再生神经纤维在管腔内呈纵行整齐排列Ｔ偕窬宋峤岣弧＝崧郏菏5验结果证实异体硬脊膜能成功地引导周围神经再生。     

移位髋臼骨折合并坐骨神经损伤

报告９例移位髋臼骨折合并坐骨神经损伤的治疗，其中单纯腓侧部损伤５例，联合腓侧部与胫侧部损伤４例。非手术治疗３例，手术治疗６例，平均随访２年，结果为手术治疗５例优良，１例可，非手术治疗２例疗效均不满意，表明手术治疗可有效复位骨折，去除神经外在压迫因素，对性质明确的神经损伤进行必要的松解和修复。本组坐骨神经损伤以腓侧部受累更为常见，腓侧部易受损伤的机理可能与某些局部解剖因素有关     

预变神经段修复神经缺损的实验研究

目的探讨不同预变时间组移植神经对神经再生的影响。方法以ＳＤ大鼠的不同预变时间组的尺神经作为移植神经，修复其正中神经的缺损。实验侧按移植神经预变时间的不同分为０、１、２、３、４、８周共６组，每组６只ＳＤ大鼠。移植后１２周，检测实验侧趾屈肌群的张力、最大收缩力、再生神经的形态及神经轴突的截面积。结果用预变１周的尺神经修复正中神经后，其趾屈肌群的张力及最大收缩力的恢复率达到正常对照组的８１．１％及８５．９％。显微镜下观察，预变１周组和其它各时间组相比，其再生的神经轴突最多，发育最成熟。结论用预变１周的神经段修复神经缺损，其神经再生能力最佳     

Stimulation of nerve growth factor and substance P expression in the iris–trigeminal axis of diabetic rats—involvement of oxidative stress and effects of aldose reductase inhibition

In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P<0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P<0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NGF, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes—a mechanism that might participate in iritis.     

Neuropathology in non-human immunodeficiency virus-infected drug addicts: hypoxic brain damage after chronic intravenous drug abuse

Neuropathological studies were carried out on 180 human immunodeficiency virus-seronegative intravenous drug addicts. The findings in victims of acute heroin intoxication (n = 116) were congestion (99.1%), capillary engorgement (68.1%), and/or perivascular bleeding (68.1%) – hemodynamic processes attributable to toxic primary respiratory failure. In a high percentage of these cases (88%), cerebral edema was also present. In 18 cases of acute heroin intoxication who survived for periods of hours or days, the sole postmortem finding was ischemic nerve cell damage, resembling that typically seen in systemic hypoxia. Semiquantitative analysis revealed nerve cell loss in the hippocampal formation and/ or Purkinje cell layer in 26% of the 162 chronic drug abusers. By contrast, in nearly 80% of these cases, the hippocampus showed enhanced expression of glial fibrillary acid protein by astrocytes and/or a proliferation of microglia, demonstrated by CD68 expression. Since such reactive processes are produced by primary neuronal damage, it can be assumed that chronic intravenous drug abuse results in obviously ischemic nerve cell loss. This could be demonstrated in the hippocampus, but it must also occur throughout the whole brain. The demonstration of ischemic nerve cell damage and neuronal loss or secondary reactive alterations has not been described previously. Received: 31 March 1995 / Revised, accepted: 27 November 1995