Metastatic prostatic adenocarcinoma to the brain and spinal cord: a contemporary clinicopathologic analysis of 30 cases

Metastatic prostatic adenocarcinoma (PCa) to lymph nodes and bone is well documented in the literature, however only case reports and small series of metastatic PCa to the brain and spinal cord with clinicopathologic analysis have been published. We identified 30 cases of metastatic PCa to the brain and spinal cord. The mean patient age was 67 years (range: 50 to 87 years). Thirteen (43%) cases involved the brain and 17 (57%) cases involved the spinal cord. Most of the cases (60%) were a single mass. Of the 13 cases involving the brain, the temporal lobe 6 (46%) was the most common site and the spinal cord lesions involved the thoracic region in 13/17 (76%) cases. All patients had one or more metastases to other organs. In 8 patients, the brain or spinal cord metastasis was the initial diagnosis of PCa. In the patients that had prior prostate biopsy specimens available, the Gleason score ranged from 3+3=6 (Grade group 1: indicating unsampled higher grade PCa) to Gleason score 4+5=9 (Grade group 5). Follow-up was available in 21 cases with a mean duration of 20 months (range: 1 to 130 months). This is one of the largest clinicopathologic studies to date of metastatic PCa to the brain and spinal cord. Although rare, metastatic PCa should be considered in the differential diagnosis of a solitary brain or spinal cord mass in male patients, even over a decade after the initial diagnosis of PCa.     

细胞来源和培养液成分对大鼠神经前体细胞增殖和分化的影响

在成功建立体外分离培养大鼠胚胎脑和脊髓神经前体细胞(neuron precursor cells,NPCs)的基础上,本研究设计了三种培养液组合:DF/N2、DF/B27和DF/(N2+B27),观察在不同培养液成分对胚胎脑和脊髓NPCs增殖和分化的影响。结果显示:与NF/N2組和DF/B27组相比,脑来源的NPCs在DF/(N2+B27)中增殖最快、最稳定(P<0.01),而脊髓来源的NPCs在三种培养液组合中的增殖速度无明显差异。脑和胚胎15 d脊髓来源的NPCs在DF/B27和DF/(N2+B27)中分化为神经元的比例明显高于DF/N2组合(P<0.01);取自胚胎15 d的脊髓NPCs分化为神经元和少突胶质细胞的比例均显著高于胚胎16 d的NPCs(P<0.05)。以上结果提示:(1)在培养液中同时添加N2和B27不仅可以提高体外培养的NPCs的增殖速度,同时可显著增加神经元分化的比例;(2)NPCs的分化潜能可因NPCs来源(脑或脊髓)和发育阶段的不同而有差异。     

Central thermosensitivity in conscious goats: Hypothalamus and spinal cord versus residual inner body

Experiments were performed on conscious goats to confirm the suggestion that in this species the inner body contains more thermosensitive structures than those residing in the hypothalamus and spinal cord. For this purpose goats were chronically implanted with local thermodes and intravascular heat exchangers to allow independent temperature control of the hypothalamus, spinal cord and residual inner body. With the hypothalamus and spinal cord clamped simultaneously at different levels between 32°C and 40°C, residual internal temperature was lowered by subtracting heat via the intravascular heat exchanger. The residual internal temperature at which shivering and increased heat production occured due to heat extraction, was directly related to the value of the combined hypothalamic and spinal cord clamp temperature. The higher hypothalamic and spinal cord clamp temperatures were, the lower residual internal temperature fell before shivering occurred and heat production rose. Plosts relating residual internal temperature to hypothalamic and spinal cord temperature at different levels of heat production showed the signal input generated within the residual inner body to be of nearly the same order of magnitude as that from the hypothalamus and spinal cord.This work was supported by DFG Je 57/3.     

A neuropeptide Y (NPY)-related peptide is present in the river lamprey CNS

Pancreatic polypeptide (PP)-like material from brain + spinal cord, and retina extracts of Lampetra fluviatilis was studied by HPLC and RIA. The brain + spinal cord extract showed a complex elution profile with multiple peaks of immunoreactivity. The retina extract showed a much simpler pattern with a single significant peak along with a trace of a second peak corresponding to the latest and penultimate peaks in the brain extract. Twenty-one out of 36 residues could be sequenced from the latest eluting peak in the brain extract. This sequence showed 81% identity with porcine neuropeptide (NPY) suggesting that both the brain/spinal cord and retina of the river lamprey contain a peptide homologous to NPY.     

Extramedullary chitosan channels promote survival of transplanted neural stem and progenitor cells and create a tissue bridge after complete spinal cord transection

Transplantation of neural stem and progenitor cells (NSPCs) is a promising strategy for repair after spinal cord injury. However, the epicenter of the severely damaged spinal cord is a hostile environment that results in poor survival of the transplanted NSPCs. We examined implantation of extramedullary chitosan channels seeded with NSPCs derived from transgenic green fluorescent protein (GFP) rats after spinal cord transection (SCT). At 14 weeks, we assessed the survival, maturation, and functional results using NSPCs harvested from the brain (brain group) or spinal cord (SC group) and seeded into chitosan channels implanted between the cord stumps after complete SCT. Control SCT animals had empty chitosan channels or no channels implanted. Channels seeded with brain or spinal cord-derived NSPCs showed a tissue bridge, although the bridges were thicker in the brain group. Both cell types showed long-term survival, but the number of surviving cells in the brain group was approximately five times as great as in the SC group. In both the brain and SC groups at 14 weeks after transplantation, many host axons were present in the center of the bridge in association with the transplanted cells. At 14 weeks astrocytic and oligodendrocytic differentiation in the channels was 24.8% and 17.3%, respectively, in the brain group, and 31.8% and 9.7%, respectively, in the SC group. The channels caused minimal tissue reaction in the adjacent spinal cord. There was no improvement in locomotor function. Thus, implantation of chitosan channels seeded with NSPCs after SCT created a tissue bridge containing many surviving transplanted cells and host axons, although there was no functional improvement.     

儿童抗髓鞘少突胶质细胞糖蛋白IgG相关疾病的MRI征象分析

目的 探讨儿童抗髓鞘少突胶质细胞糖蛋白IgG相关疾病（MOGAD）的MRI特征。方法 病例系列报告。纳入2018年1月—2021年12月聊城市人民医院确诊MOGAD的10例患儿,其中男6例、女4例,年龄2~9（5.9±2.4）岁。10例患儿治疗前行颅脑MR常规扫描,9例行全脊柱MR常规扫描,4例行眼眶MR常规扫描。观察指标：（1）记录MRI对MOGAD颅脑、脊髓和视神经病变的检出情况;（2）总结颅脑MOGAD病变分布位置、形态及信号特点;（3）观察脊髓MOGAD病变部位、脊髓有无肿胀,统计长节段脊髓MOGAD病变的患儿数量;（4）观察视神经病变部位、视神经有无肿胀;（5）将患儿末次随访时复查MRI与治疗前进行对比,观察病变转归情况。结果 治疗前MRI显示：（1）颅脑病变10例,脊髓病变5例,视神经病变2例。（2）10例MOGAD颅脑病变均为多发,9例双侧、1例单侧。4例仅累及幕上,1例仅累及幕下,5例同时累及幕上和幕下。幕上病变位于皮层下白质7例,脑室周围白质7例,丘脑5例,基底节区4例,胼胝体2例,单侧皮质1例;幕下病变位于桥脑6例,同时累及小脑4例、中脑2例。病变均为非对称性。MOGAD病变形态均表现为无定形斑片状、斑点状,其中2例同时出现斑块样改变;2例病变DWI序列显示弥散受限。（3）MOGAD脊髓病变5例,均为单发、累及胸段脊髓的长节段脊髓病变,其中4例同时累及颈段脊髓,未发现腰段脊髓受累;2例出现脊髓肿胀。（4）MOGAD视神经病变2例,均为双侧,其中1例视神经全程受累、1例视神经前部受累,视交叉及视束均无受累。2例视神经均无肿胀。（5）10例患儿经治疗后均好转出院,出院后随访8~29（12.9±5.8）个月。随访期间患儿定期复查MRI,均未见复发。末次随访MRI显示,2例患儿颅脑病变完全消失,1例脊髓病变完全消失,其余7例患儿颅脑、脊髓或视神经MOGAD病变范围均减小或病灶数均减少。结论 儿童MOGAD中,颅脑病变最常见,其次为脊髓和视神经;不同部位的MOGAD MRI表现具有一定特征性,认识这些影像学特征,可以提高临床医生诊断儿童MOGAD的准确率,为早期治疗提供重要参考。     

Latency of Herpes Simiae (B virus) in rabbits.

When small doses of herpes simplex virus (HSV) were given to rabbits a significant degree of protection was afforded against later infection with herpes simiae (B virus). Only 12/47 rabbits died within 3 weeks of receiving B virus dosages that would normally have proved lethal. B virus became latent in survivors and was recovered from brain and spinal cord suspensions from rabbits which died within 6 months and from dorsal root ganglia of rabbits which had survived for more than 2 years without overt signs of infection. A minority of the survivors tested also yielded HSV. Rabbits with latent B virus in the ganglia showed little or no detectable neutralizing antibody to B virus. The possibility is discussed that human populations having a high frequency occurrence of HSV antibody may include carriers of latent B virus.     

MAP2 and neurogranin as markers for dendritic lesions in CNS injury. An immunohistochemical study in the rat

We compared two staining methods for the demonstration of dendrites under normal and pathological conditions of the rat central nervous system. MAP2- and neurogranin immunohistochemistry was applied to samples from normal tissue, spinal cord subjected to graded compression trauma, cerebral cortex following contusion trauma, and brains with focal ischemic lesions induced by occlusion of the middle cerebral artery (MCAO). Normal rats showed MAP2 immunoreactivity in nerve cell bodies and dendrites of brain and spinal cord. However, neurogranin staining was present only in nerve cell bodies and dendrites of the normal brain, and not in the spinal cord.
Reduction of MAP2 immunoreactivity was seen in lesions of spinal cords subjected to compression trauma. Neurogranin staining was of no value in this experimental condition since it was not present under normal conditions. The brain contusions showed loss of both MAP2- and neurogranin immunoreactivity at the site of the lesion. MCAO resulted in an extensive loss of MAP2- and neurogranin staining in the ipsilateral hemisphere.
In conclusion, our study shows that MAP2 immunostaining is a sensitive method for identifying dendritic lesions of various CNS injuries in the rat. Neurogranin immunostaining is an alternative method for investigations of dendritic pathology in the brain but not in the spinal cord.     

Isolated spinal cord neurosarcoidosis diagnosed by cord biopsy and thalidomide trial

We report a case of 54-yr-old woman who presented with 4-extremities weakness and sensory changes, followed by cervical spinal cord lesion in magnetic resonance imaging. Based on the suspicion of spinal tumor, spinal cord biopsy was performed, and the histology revealed multinucleated giant cells, lymphocytes and aggregated histiocytes within granulomatous inflammation, consistent with non-caseating granuloma seen in sarcoidosis. The patient was treated with corticosteroid, immunosuppressant and thalidomide for years. Our case indicates that diagnosis of spinal cord sarcoidosis is challenging and may require histological examination, and high-dose corticosteroid and immunosuppressant will be a good choice in the treatment of spinal cord sarcoidosis, and the thalidomide has to be debated in the spinal cord sarcoidosis.     

New Minimally Invasive Model of Spinal Cord Ischemia in Rats

We developed a new minimally invasive model of spinal cord ischemia in rats: intravascular occlusion of the abdominal aorta and its branches. This model can be used on small laboratory animals and allows qualitatively and quantitatively evaluating the morphofunctional state of the nervous system during spinal cord ischemia by clinical manifestations and histological changes. Selective intravascular occlusion determines minimal invasiveness and adequacy of the proposed model to in vivo pathological processes. This model of spinal cord ischemia can be used in experimental pharmacology for evaluation of neuroprotective activity of various drugs and bioactive substances.     

Brain natriuretic peptide in the porcine spinal cord: an immunohistochemical investigation of its localization and the comparison with atrial natriuretic peptide, substance P, calcitonin gene-related peptide, and enkephalin

Immunohistochemistry was used to localize brain natriuretic peptide in the porcine spinal cord and to compare it with that of atrial natriuretic peptide, substance P, calcitonin gene-related peptide and [Met]enkephalin. Brain natriuretic peptide-immunoreactive varicose fibers were observed in lamina I and the inner portion of lamina II of the dorsal horn. Semiquantitative analysis showed that the highest density of brain natriuretic peptide-immunoreactive varicosities was in the lumbosacral and coccygeal segments. The distributional pattern of brain natriuretic peptide-immunoreactive nerve fibers in the spinal cord was unique and quite distinct from that of the other neuropeptides studied. These neuroanatomical findings suggest that brain natriuretic peptide may play a role in the regulation of nociceptive processing in the spinal cord, either alone or with bioactive substances.     

Neural toxicity induced by accidental intrathecal vincristine administration

Described here is a case of accidental intrathecal administration of vincristine with pathologic findings in the central nervous system. A 3-year-old boy with acute lymphoblastic leukemia, was given his ninth course chemotherapy. Vincristine was accidentally injected intrathecally. The clinical course was rapidly progressive (6-day course) and resulted in death. An autopsy was done. The brain and spinal cord was grossly edematous and congested without any specific feature. Histologically, profound loss of neuron was noted in the spinal cord. Remaining neurons in the spinal cord, particularly anterior horn cells were markedly swollen. The spinal nerves show diffuse axonal degeneration and myelin loss. The upstream portion of the spinal cord (brain stem, cerebellum, cerebrum) showed patchy loss of neurons, especially Purkinje cells and granular cells of the cerebellar cortex. Many neurons showed axonal reaction (chromatolysis) with swelling. Several neurons show intracytoplasmic eosinophilic inclusion body. Myelin loss, axonal swelling and enlargement of perivascular spaces were seen throughout the white matter of central nervous system.     

Craniospinal dissemination of clival chondroid chordoma

Chondroid chordoma commonly presents as clival osseous and extradural mass. A 15-year-old boy presented with progressive visual deficit, headaches and diplopia since three years. Computed tomography (CT scan) showed a skull base tumour, but was wrongly reported at the time as chronic sphenoidal sinusitis and nasal polyps. In the past three months, he developed dysphagia, urinary retention and constipation. Terminally, he had weakness of all limbs. Fundoscopy showed optic atrophy. Temporal and spatial variation in symptoms led to a clinical diagnosis of multiple sclerosis with optic neuritis. Partial brain autopsy revealed small gelatinous tumour nodules in the subarachnoid space of middle cranial fossa encasing base of brain like arachnoiditis. Tumour deposits extended down into the spinal cord along the subarachnoid space as far as vision allowed. Histopathology and immunohistochemistry confirmed a diagnosis of chondroid chordoma. Awareness of this rare mode of dissemination will avoid misdiagnosis and delay in treatment.     

Total body thermosensitivity and its spinal and supraspinal fractions in the conscious goose

1. Effects of general body cooling on heat production: an intravascular heat exchanger was used to alter total body temperature. Heat production increased with decreasing body temperature at an average rate of ?12 W/kg·°C. The rate of rise was independent of air temperature. The threshold body temperature below which heat production rose was lower at higher air temperature.
2. Effects of spinal cord cooling: heat production increased with decreasing spinal temperature at an average rate of ?0.3 W/kg·°C. The rate of rise was not clearly affected by air temperature. The spinal threshold temperature was lower at warm ambient conditions. The results suggest that spinal thermosensitivity in the goose represents only a minor fraction of total body thermosensitivity.
3. Effects of head cooling: heat exchangers enclosing the carotid arteries were used to alter the temperature of the blood supplied to the head. Cooling increased heat production. When the thermosensitivity of the area, which was affected by the heat exchanger, was calculated from the relationship between changes of heat production and brain temperature, values between ?0.74 and ?1.65 W/kg·°C were obtained. Measurements of brain, spinal cord and head skin temperatures suggest that the thermosensitive structures which mediated the responses, were predominantly situated in the brain.

     

Bradykinin preconditioning induces protective effects on the spinal cord ischemic injury of rats

The study was performed to investigate the effects of bradykinin preconditioning on spinal cord ischemic injury using an in vivo transient spinal cord ischemia model in rats. Prior to ischemia, bradykinin was infused continuously via the left femoral artery starting 15min before ischemia. Neurological functions were evaluated for 7 days postoperatively using modified Tarlov's scores. Tarlov's score outcomes showed a marked improvement in the bradykinin group compared to the ischemia group. The blood-spinal cord barrier (BSCB) permeability was also decreased by bradykinin preconditioning after 72 h reperfusion focal spinal cord in rats, which was greatly reversed by B9430 (bradykinin B2 receptor antagonist). Immunohistochemical and Western blot analysis of spinal cords revealed a significant increase in basic fibroblast growth factor protein (bFGF) levels. The study demonstrated that bradykinin preconditioning induces protection against spinal cord ischemic injury, and this protection is likely due to the protection of the vasculature of the spinal cord and the promotion of neuronal survival.     

Neurological deficits and glycosphingolipid accumulation in saposin B deficient mice

Saposin B derives from the multi-functional precursor, prosaposin, and functions as an activity enhancer for several glycosphingolipid (GSL) hydrolases. Mutations in saposin B present in humans with phenotypes resembling metachromatic leukodystrophy. To gain insight into saposin B's physiological functions, a specific deficiency was created in mice by a knock-in mutation of an essential cysteine in exon 7 of the prosaposin locus. No saposin B protein was detected in the homozygotes (B-/-) mice, whereas prosaposin, and saposins A, C and D were at normal levels. B-/- mice exhibited slowly progressive neuromotor deterioration and minor head tremor by 15 months. Excess hydroxy and non-hydroxy fatty acid sulfatide levels were present in brain and kidney. Alcian blue positive (sulfatide) storage cells were found in the brain, spinal cord and kidney. Ultrastructural analyses showed lamellar inclusion material in the kidney, sciatic nerve, brain and spinal cord tissues. Lactosylceramide (LacCer) and globotriaosylceramide (TriCer) were increased in various tissues of B-/- mice supporting the in vivo role of saposin B in the degradation of these lipids. CD68 positive microglial cells and activated GFAP positive astrocytes showed a proinflammatory response in the brains of B-/- mice. These findings delineate the roles of saposin B for the in vivo degradation of several GSLs and its primary function in maintenance of CNS function. B-/- provide a useful model for understanding the contributions of this saposin to GSL metabolism and homeostasis.     

Congenital spinal cord malformation concurrent with ependymoma of the third brain ventricle

This paper describes a very rare case of congenital spinal cord malformation as two tumoroid masses of spinal cord rudiments and located in the area of the cauda equina. In addition, ependymoma of the third brain ventricle was detected in a male child aged 2 years and 4 months.     

硫酸软骨素酶ABC对大鼠脊髓损伤修复的影响

为了探讨硫酸软骨素酶ABC对脊髓损伤后损伤局部瘢痕形成和脊髓传导功能修复的影响,本研究首先制作大鼠脊髓全横断损伤动物模型,并将其分为脊髓损伤组(A组)和脊髓损伤治疗组(B组)。在观察期内对动物的行为学表现进行BBB评分;用免疫荧光组织化学方法观察损伤4周后硫酸软骨素酶ABC对损伤局部的硫酸软骨素蛋白聚糖(CSPGs)的裂解作用;用辣根过氧化物酶(HRP)示踪法观察损伤8周后神经纤维的再生情况。结果显示:A组与B组之间动物的行为学评分B组优于A组,有显著性差异(P<0.01);B组动物脊髓内硫酸软骨素蛋白聚糖阳性物质的表达明显低于A组,具有显著性差异(P<0.05),而硫酸软骨素核心蛋白的表达无显著性差异(P>0.05);HRP示踪法显示B组脊髓损伤头端可见少量HRP标记的神经元胞体和纤维。本研究结果提示硫酸软骨素酶ABC能够裂解CSPGs中的葡胺聚糖链,减少瘢痕,促进损伤的神经纤维再生。     

New onset focal weakness in children with Down syndrome

New onset focal weakness is relatively common in patients with Down syndrome (DS), and has broad differential diagnosis. Ten cases of new onset focal weakness in patients with DS were encountered or are currently being followed in two DS clinics, with a combined population of patients of approximately 850, for a clinic population prevalence of 1.2%. The median age at presentation was 4 years old (range 1 month-44 years). The causes of new onset focal weakness were: stroke from Moyamoya disease (two patients); stroke from vaso occlusive disease (one patient); stroke from venus sinus thrombosis (one patient); traumatic subdural hematoma (one patient); brain abscess (one patient); spinal cord injury (SCI) from cervical spinal stenosis (two patients); SCI from atlantoaxial instability (AAI) (one patient); and brachial plexus injury (one patient). Of the 10 patients with focal weakness, 8 had potentially treatable conditions, and 5 had surgery. The differential diagnosis of new onset focal weakness in DS is broad, with diseases reported involving all levels of the nervous system from brain to muscle. For some diagnoses, expeditious diagnosis may improve outcome.     

Dynorphin A content in the rat brain and spinal cord after a localized trauma to the spinal cord and its modification with p-chlorophenylalanine. An experimental study using radioimmunoassay technique.

The distribution of dynorphin A in the spinal cord and brain of normal rats and of rats subjected to a focal injury of the spinal cord was examined in a rat model using a radioimmunoassay (RIA) technique. The validity of RIA was checked by high performance liquid chromatography (HPLC). Furthermore, the possibility that the peptide is somehow functionally related with endogenous 5-hydroxytryptamine (5-HT, serotonin), was also evaluated using a pharmacological approach. In normal animals, the peptide content was very similar in the spinal cord segments (T9, T10-11, and T12) examined whereas, the dynorphin content of the whole brain was about two-fold higher compared with that in the spinal cord. A focal injury to the spinal cord in the right dorsal horn (about 1.5 mm deep, 2.5 mm long and 1.5 mm to the right of the midline) of the lower thoracic cord (T10-11) in urethane anaesthetised animals significantly altered the peptide content in the whole brain as well as in the spinal cord. Thus, a decrease in the peptide level in whole brain, T10-11 and in the T12 segments of the spinal cord was observed 1 and 2 h after trauma. At 5 h, the peptide had accumulated markedly in the T9 segment (about a two-fold increase) as compared with the controls. At this time, the peptide content had been restored in the T10-11 and T12 segments. On the other hand, the whole brain dynorphin level continued to remain low (by 55%) as compared to the control group.(ABSTRACT TRUNCATED AT 250 WORDS)