Neuroimaging and Neurologic Complications after Organ Transplantation

Neurologic complications are common after transplantation and affect 30-60% of transplant recipients. The etiology of most of the posttransplant neurologic disorders is related to the opportunistic infections, both systemic and involving central nervous system (CNS), toxicity of immunosuppressive medications, and the metabolic insult created by the underlying primary disease and the transplant procedure. Neuroimaging studies are one of the key tools in the evaluation and enable early diagnosis of neurologic complications in transplant patients, especially posterior reversible leukoencephalopathy syndrome, central pontine myelinolysis, intracerebral hemorrhage, and fungal and bacterial abscesses. Magnetic resonance imaging (MRI) is the preferred technique, but each of the available neuroimaging techniques offers a unique insight into the pathophysiologic mechanisms underlying neurologic complications of transplantation. The role of neuroimaging in this population includes early detection of calcineurin inhibitor neurotoxicity, opportunistic infections, neoplasia, metabolic disorders, or cerebrovascular diseases. In addition, we can monitor longitudinal progression of disease and treatment response.     

旁正中动脉入口部梗死82例临床分析

目的探讨急性桥脑旁正中动脉入口部梗死(branch atheromatous disease,BAD)的临床特点。方法回顾性分析1997～2003年本院神经内科收治的82例桥脑BAD的临床表现、MRI影像特点、脑干听觉诱发电位(BAEP)表现、危险因素。结果本组病例的临床特点是:平均发病年龄69.2岁,男性/女性=46/36,56/82病情呈进行性发展,75/82有构音障碍,72/82有肢体偏瘫,29/82为高度肢体瘫痪,27/82有轻度意识障碍,6/82伴有不全Homer征,49/82出现面部或(和)偏侧肢体感觉减退,25/82出现周围性面瘫,42/82有非旋转性头晕;13/82有眼球运动障碍。MRI表现有:梗死灶位于桥脑中上部、达桥脑表面,楔形,内侧位于桥脑旁正中、呈类似直线,可显示出基底动脉壁不整;危险因素方面除高血压外还与糖尿病、脂质代谢异常有关。结论根据临床特点及MRI表现正确诊断出桥脑BAD,以指导进一步的病因治疗及预防。     

微电脑促醒仪的研制

介绍微电脑促醒仪的基本结构、工作原理、主要技术特点及临床应用等内容。该仪器运用微电脑控制的促醒仪产生电刺激信号，通过射频耦合方式(或直接耦合方式)传递到植物生存状态患者脑干网状结构刺激电极，激活网状激动系统，促使Pcrsistent Vegtative State，PVS患者康复，取得了较好的效果。     

A lectin horseradish peroxidase study of the origin of ascending fibers in the medial forebrain bundle of the rat. The upper brainstem

The origins of projections within the medial forebrain bundle from the upper brainstem were examined with the horseradish peroxidase technique. Labeled cells were found in approximately 15 upper brainstem nuclei following injections of a conjugate of horseradish peroxidase and wheat germ agglutinin at various levels of the medial forebrain bundle. Labeled nuclei included (from caudal to rostral): dorsal and ventral parabrachial nuclei; Kolliker-Fuse nucleus; dorsolateral tegmental nucleus; A7 (lateral pontine tegmentum medial to lateral lemniscus); median and dorsal raphe nuclei; distinct group of cells oriented mediolaterally in the dorsal pontine tegmentum below the central gray; B9 (ventral midbrain tegmentum dorsal to medial lemniscus); retrorubral nucleus; nucleus of Darkschewitsch, interfascicular nucleus; rostral and caudal linear nuclei; ventral tegmental area; medial part of substantia nigra, pars compacta; and the supramammillary nucleus. With the exception of the ventral parabrachial nucleus, Kolliker-Fuse, A7, B9 and substantia nigra, pars compacta, each of the nuclei mentioned above sent strong projections along the medial forebrain bundle to the rostral forebrain. Sparse labeling was observed throughout the pontine and midbrain reticular formation. With the exception of the dorsal raphe nucleus, projections to the most anterior regions of the medial forebrain bundle (level of the anterior commissure) essentially only arose from presumed dopamine-containing nuclei-retrorubral nucleus (A8 area), interfascicular nucleus, rostral and caudal linear nuclei, substantia nigra pars compacta, and ventral tegmental area. Evidence was reviewed indicating that major forebrain sites of termination for these dopaminergic nuclei are structures that have been collectively referred to as the 'ventral striatum'. It is concluded from the present findings that several pontine and mesencephalic cell groups are in a position to exert a strong, direct effect on structures in the anterior forebrain and that the medial forebrain bundle is the main communication route between the upper brainstem and the forebrain.     

Reversible “locked-in” syndromes

Two young patients are described who made good recoveries from a locked-in syndrome presumed to be due to ventral pontine ischemia. The first patient recovered completely from quadriplegia and mutism. In the second patient the only permanent sequellae were slight dysarthria and mild spasticity. Since patients may recover nearly completely from a locked-in syndrome, aggressive supportive therapy seems justified during the initial weeks or months.     

Long-term enhancement of REM sleep by the pituitary adenylyl cyclase-activating polypeptide (PACAP) in the pontine reticular formation of the rat

In rats, rapid eye movement (REM) sleep can be elicited by microinjection of vasoactive intestinal polypeptide (VIP) into the oral pontine reticular nucleus (PnO). In the present study, we investigated whether this area could also be a REM-promoting target for a peptide closely related to VIP: the pituitary adenylyl cyclase-activating polypeptide (PACAP). When administered into the posterior part of the PnO, but not in nearby areas, of freely moving chronically implanted rats, PACAP-27 and PACAP-38 (0.3 and 3 pmol) induced a marked enhancement (60-85% over baseline) of REM sleep for 8 h that could be prevented by prior infusion of the antagonist PACAP-(6-27) (3 pmol) into the same site. Moreover, injections of PACAP into the centre of the posterior PnO resulted in REM sleep enhancement which could last for up to 11 consecutive days. Quantitative autoradiography using [125I]PACAP-27 revealed the presence in the PnO of specific binding sites with high affinity for PACAP-27 and PACAP-38 (IC50 = 2.4 and 3.2 nM, respectively), but very low affinity for VIP (IC50 > 1 microM). These data suggest that PACAP within the PnO may play a key role in REM sleep regulation, and provide evidence for long-term (several days) mechanisms involved in such a control. PAC1 receptors which have a much higher affinity for PACAP than for VIP might mediate this long-term action of PACAP on REM sleep.     

Molecular alterations in pediatric brainstem gliomas

1 Background

Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis. Previously, diagnosis was based on a typical clinical presentation and magnetic resonance imaging findings. After the start of the era of biopsies, DIPGs bearing H3 K27 mutations have been reclassified into a novel entity, diffuse midline glioma, based on the presence of this molecular alteration. However, it is not well established how clinically diagnosed DIPG overlap with H3 K27‐mutated diffuse midline gliomas, and whether rare long‐term survivors also belong to this group.

2 Methods

We studied tumor samples obtained at diagnosis or upon autopsy from 23 children, including two long‐term survivors. Based on clinical, radiological, and histological findings, all tumors were previously diagnosed as DIPGs. All samples were analyzed for genetic alterations by next‐generation sequencing (NGS) and for protein expression by immunohistochemistry (IHC).

3 Results

H3 K27 was mutated in NGS or IHC in 20 patients, excluding both long‐term survivors. One of these long‐term survivors harbored a mutation in IDH1, formerly considered to be an alteration absent in pediatric diffuse brainstem gliomas. Other altered genes in NGS included TP53 (10 patients), MET and PDGFRA (3 patients each), VEGFR and SMARCA4 (2 patients each), and PPARγ, PTEN and EGFR in 1 patient, respectively. IHC revealed cMYC expression in 15 of 24 (63%) of all samples, exclusively in the biopsies.

4 Conclusions

Eighty‐seven percent of the tumors formerly diagnosed as DIPGs could be reclassified as H3 K27‐mutated diffuse midline gliomas. Both long‐term survivors lacked this alteration. Contrary to former conceptions, IDH1 mutations may occur also in pediatric brainstem gliomas.     

脑桥中央髓鞘溶解症(附3例报告)

目的探讨脑桥中央髓鞘溶解症（CPM）的病因、临床特点、治疗及其预防措施。方法回顾性分析3例已确诊的CPM患者的诊断资料。结果3例患者均存在严重的基础病症,特别是严重的电解质紊乱（低钠血症）,过快纠正后出现球麻痹,四肢瘫痪;头颅磁共振成像（MRI）改变。经激素、脱水剂、B族维生素等治疗,均好转出院。结论营养不良或（和）电解质紊乱是CPM常见的基础疾病,纠正电解质紊乱不宜过快,头颅MRI对本病早期确诊意义较大,早期诊断适当治疗,预后良好。