MRI findings for diagnosis of postoperative foreign body granulomas versus recurrent tumours in patients of brain tumour surgery.

AIM: To evaluate the postoperative magnetic resonance imaging (MRI) findings of intracranial foreign body granulomas (FBGs) and true recurrent tumours (RTs) and thus lead to a basis for management decision-making. MATERIALS AND METHODS: Twenty-two patients with previous brain tumour surgery were diagnosed clinically with RT and underwent surgery. Re-operative pathology revealed FBG in eight patients and RT in 14 patients. MRI findings before the initial operation were compared to those before the re-operation. RESULTS: Features of FBGs versus RTs on MRI were as follows: (1) mean lesion size: 1.3 ± 0.7 (0.5-2.6) versus 3.2 ± 1.7 (1.1-6.3) cm (p=0.001, odds ratio [OR] = 4.18); (2) hypointensity on T2-weighted imaging (WI): 6/8 (75%) versus 0/14 (0%; p<0.001, OR=75.4); (3) non-restricted diffusion on diffusion-WI (DWI): 6/8 (75%) versus 2/14 (14.3%; p=0.008, OR=18); and (4) "ring and bubble" appearance on contrast-enhanced T1WI: 7/8 (87.5%) versus 2/14 (14.3%; p=0.001, OR=42). In comparison with their original tumours, the FBGs in the FBG group showed significantly lower T2 signal intensity, lower signal on DWI, and more cases of non-restricted diffusion on DWI (p=0.04, 0.04, 0.04, respectively). CONCLUSION: On brain MRI, FBGs can be differentiated from RTs by their relatively smaller size, hypointensity on T2WI, lack of restricted diffusion on DWI, and "ring and bubble" appearance on contrast-enhanced T1WI. Comparing the MRI findings of the focal lesion in the tumour bed with those of the original tumour is suggested to enhance diagnostic confidence.

Clinical epidemiology and outcome of HIV-associated talaromycosis in Guangdong, China, during 2011-2017.

OBJECTIVES: Talaromycosis is an invasive mycosis endemic to Southeast Asia. This study aimed to investigate the epidemiology, clinical features and prognostic factors of HIV-associated talaromycosis in Guangdong, China. METHODS: We retrospectively evaluated HIV patients hospitalized with histopathology- or culture-confirmed talaromycosis between 2011 and 2017. Factors associated with poor prognosis were identified using logistic regression. RESULTS: Overall, 1079 patients with HIV-associated talaromycosis were evaluated. Both the number and prevalence of talaromycosis among HIV admissions increased from 125 and 15.7% in 2011 to 253 and 18.8% in 2017, respectively, reflecting the increase in HIV admissions. Annual admissions peaked during the rainy season between March and August. Common clinical manifestations included fever (85.6%), peripheral lymphadenopathy (72.3%), respiratory symptoms (60.8%), weight loss (49.8%), skin lesions (44.5%) and gastrointestinal symptoms (44.3%). Common laboratory abnormalities were hypoalbuminaemia (98.6%), anaemia (95.6%), elevated aspartate aminotransferase level (AST) (76.9%), elevated alkaline phosphatase level (55.8%) and thrombocytopenia (53.7%). The median CD4 count was 9 cells/µL. Talaromyces marneffei was isolated from blood and bone marrow cultures of 66.6% and 74.5% of patients, respectively. The rate increased to 86.6% when both cultures were performed concurrently. At discharge, 14% of patients showed worsening conditions or died. Leucocytosis, thrombocytopenia, elevated AST, total bilirubin, creatinine and azole monotherapy independently predicted poor prognosis. CONCLUSIONS: The incidence of HIV-associated talaromycosis has increased in Guangdong with the high HIV burden in China. Skin lesions were seen in less than half of patients. Induction therapy with azole alone is associated with higher mortality. Findings from this study should help to improve treatment of the disease.

Evaluation of the outcomes of endovascular management for patients with head and neck cancers and associated carotid blowout syndrome of the external carotid artery.

AIM: To evaluate factors related to the technical and haemostatic outcomes of endovascular management in patients with head and neck cancers (HNC) associated with carotid blowout syndrome (CBS) of the external carotid artery (ECA). MATERIALS AND METHODS: Between 2002 and 2011, 34 patients with HNC with CBS involving branches of the ECA underwent endovascular therapy. Treatment included embolization with microparticles, microcoils, or acrylic adhesives. Fisher's exact test was used to examine demographic features, clinical and angiographic severities, and clinical and imaging findings as predictors of endovascular management outcomes. RESULTS: Technical success and immediate haemostasis were achieved in all patients. Technical complications were encountered in one patient (2.9%). Rebleeding occurred in nine patients (26.5%). Angiographic vascular disruption grading from slight (1) to severe (4) revealed that the 18 patients with acute CBS had scores of 2 (2/18, 11.1%), 3 (3/18, 16.7%), and 4 (13/18, 72.2%). The 16 patients with impending and threatened CBS had scores of 1 (1/16, 6.25%), 2 (5/16, 31.25%), and 3 (10/16, 62.5%; p = 0.0003). For the 25 patients who underwent preprocedural computed tomography (CT)/magnetic resonance imaging (MRI) examinations within 3 months of treatment, the agreement between clinical and imaging findings reached the sensitivity, specificity, and kappa values for recurrent tumours (1, 0.7143, 0.7826), soft-tissue defect (0.9091, 0.3333, 0.2424), and sinus tract/fistula (0.4737, 0, 0.4286). CONCLUSION: Endovascular management for patients with CBS of the ECA had high technical success and safety but was associated with high rebleeding rates. We suggest applying aggressive post-procedural follow-up and using preprocedural CT/MRI to enhance the periprocedural diagnosis.

Development of a fluorescent-intercalating-dye-based reverse transcription loop-mediated isothermal amplification assay for rapid detection of seasonal Japanese B encephalitis outbreaks in pigs.

The standardization and validation of a one-step, single-tube, accelerated fluorescent-intercalating-dye-based reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay targeting the NS3 gene of Japanese B encephalitis virus (JEV) is described for rapid, simple, and high-throughput detection of JEV. The amplification can be completed in 35 min under isothermal conditions at 63°C by employing a set of six primers targeting the NS3 gene of JEV. The RT-LAMP assay described demonstrated high sensitivity for detecting JEV, with a detection limit in swine samples of 8.13 PFU/ml. The specificity of the selected primer sets was established by cross-reactivity studies with pathogens that exhibit similar clinical signs and testing of samples from healthy animals. The clinical applicability of the RT-LAMP assay was validated using either spiked samples or samples from seasonal outbreaks. The comparative evaluation of the RT-LAMP assay revealed 79.59 % concordance with conventional RT-PCR targeting the E gene of JEV. The RT-LAMP assay reported here is a valuable tool for rapid real-time and high-throughput seasonal infection surveillance and quarantine after outbreak through blood sampling by using ordinary real-time PCR thermocyclers without purchasing an expensive Loopamp real-time turbidimeter.

Direct puncture of a prematurely detached balloon in the supraclinoid ICA via the optic canal during embolisation of a traumatic carotid-cavernous fistula.

We report a patient with traumatic carotid-cavernous fistula associated with an isolated internal carotid artery in whom, after trans-arterial balloon embolisation, premature balloon detachment occurred with balloon migration to the supraclinoid carotid artery, leading to total occlusion of the blood flow. The carotid flow was eventually restored by direct puncture of the detached balloon via the optic canal and by deploying a coronary stent to fix the balloon in the vascular wall. The fistula was eventually occluded by using detachable coils. He was discharged with a mild hemiparesis and decreased acuity in the left eye.

Morphologic Change of Flow-Related Aneurysms in Brain Arteriovenous Malformations after Stereotactic Radiosurgery.

BACKGROUND AND PURPOSE: The natural history of flow-related aneurysms after obliteration of brain arteriovenous malformations is poorly understood. The purpose of this study was to evaluate the angioarchitecture and morphologic change in flow-related aneurysms after gamma knife surgery of brain arteriovenous malformations. MATERIALS AND METHODS: During a 12-year period, 823 patients with brain arteriovenous malformations underwent gamma knife surgery at our institution with complete peritherapeutic angiographic evaluation. From this population, a series of 72 patients (8.8%) with 111 flow-related aneurysms were enrolled (1.5 aneurysms per patient). There were 43 men and 29 women; ages ranged from 18 to 72 years (mean, 43 years). The morphologic change of flow-related aneurysms was longitudinally evaluated before and after obliteration of brain arteriovenous malformations. After gamma knife surgery, angiographic follow-up varied from 26 to 130 months (mean, 58 months). RESULTS: All flow-related aneurysms were small (mean, 4.1 mm; range, 2-9 mm). There were 72 proximal flow-related aneurysms (mean size, 4.3 mm) and 39 distal flow-related aneurysms (mean size, 3.7 mm). Spontaneous thrombosis occurred more frequently in distal flow-related aneurysms than in proximal flow-related aneurysms (P < .001). Smaller flow-related aneurysms (<5 mm) tended to spontaneously occlude after obliteration of brain arteriovenous malformations (P = .036). Two patients had ruptures of proximal flow-related aneurysms at 27- and 54-month follow-ups, respectively. CONCLUSIONS: Spontaneous thrombosis occurred more frequently in distal flow-related aneurysms due to occlusion or normalization of distal feeders. Smaller flow-related aneurysms also tended to spontaneously thrombose after obliteration of brain arteriovenous malformations. The rate of flow-related aneurysm rupture in our series was similar to that of natural intradural aneurysms.

Polymorphism in dural arteriovenous fistula: matrix metalloproteinase-2-1306 C/T as a potential risk factor for sinus thrombosis.

Essentials Sinus thrombosis may play a crucial role in development of dural arteriovenous fistula (DAVF). Little is known about the association between gene polymorphism and the development of DAVF. MMP-2-1306 C/T showed a higher prevalence rate in DAVF cases with sinus thrombosis. MMP-2-1306C/T polymorphism is likely a potential risk factor for sinus thrombosis in DAVF. SUMMARY: Background Dural arteriovenous fistula (DAVF) is a rare but important cerebrovascular disorder in adults. Little is known about the molecular genetic pathogenesis underlying DAVF development. Objectives To investigate the associations of gene polymorphisms and DAVF. Materials and Methods By the use of real-time PCR genotyping, seven single-nucleotide polymorphisms (SNPs) of angiogenesis-related genes were analyzed in 72 DAVF patients. Pertinent clinical and imaging data were subgrouped on the basis of location (cavernous sinus versus lateral sinus), lesions (single versus multiple), cerebral venous reflux (CVR) grading (Borden I versus Borden II/III), and sinus thrombosis (with versus without). Results We found that individuals carrying the polymorphic allele of matrix metalloproteinase (MMP)-2-1306 C/T (rs243865) had a significantly increased risk of sinus thrombosis in DAVF (odds ratio 6.2; 95% confidence interval 1.7-22.9). There was a weak difference in associations of tissue inhibitor of metalloproteinase (TIMP)-2 (rs2277698) gene polymorphism and DAVF patients subgrouped by CVR grading. Conclusions These preliminary results indicate that MMP-2-1306 C/T, but not MMP-9, TIMP-1, TIMP-2, and vascular endothelial growth factor A SNP variants, is a risk factor for the development of sinus thrombosis in DAVF patients.

Carotid blowout syndrome in patients with head-and-neck cancers: reconstructive management by self-expandable stent-grafts.

BACKGROUND AND PURPOSE: Some reports of reconstructive management of carotid blowout syndrome (CBS) with stent-grafts are promising, but some are unfavorable. This study sought to evaluate the hemostatic efficacy, safety, and outcome of reconstructive, endovascular stent-graft placement in patients with head-and-neck cancers in association with CBS. METHODS: Eight patients with head-and-neck cancers with CBS were treated with self-expandable stent-grafts. We evaluated the initial hemostatic results, complications, and outcomes by assessing the clinical and imaging findings. RESULTS: Immediate hemostasis was achieved in all patients. Initial complications included stroke in 1 patient and asymptomatic thrombosis of the carotid artery in 2 patients. Delayed complications included rebleeding, delayed carotid thrombosis, and brain abscess formation. Rebleeding was noted in 4 patients and was successfully managed with a second stent-graft and embolization in 2 of them. Delayed carotid thrombosis with follow-up after 3 months was found in 3 patients, 1 of whom had associated brain abscesses. CONCLUSION: Although stent-grafts achieved immediate and initial hemostasis in patients with head-and-neck cancers and CBS, long-term safety, stent patency, and permanency of hemostasis appeared unfavorable. This treatment may be for temporary or emergency purposes rather than serving as a permanent measure. We suggest its applications in patients with acute CBS that precludes performance of an occlusion test, as well as when carotid occlusion poses an unusually high risk of neurologic morbidity. We also propose prophylactic antibiotic treatment and combined embolization of pathologic vascular feeders to improve outcomes.

Segmental neurovascular syndromes in children.

The concept of segmental vascular syndromes with different, seemingly unrelated, diseases is based on the embryology of the neural crest and the mesoderm migration of cells that share the same metameric origin. Migrating patterns of these cells link the brain, the cranial bones, and the face on the same side. A somatic mutation developing in the region of the neural crest or the adjacent cephalic mesoderm before migration can, therefore, be postulated to produce arterial or venous metameric syndromes, including PHACES, CAMS, Cobb syndrome, and Sturge-Weber syndrome. Although these diseases may be rare, their relationships among each other and their postulated linkage with the development of the neural crest and the cephalic mesoderm may shed light on the complex pathology and etiology of various cerebral vascular disorders.

Transarterial balloon-assisted n-butyl-2-cyanoacrylate embolization of direct carotid cavernous fistulas.

BACKGROUND AND PURPOSE: Transarterial detachable balloon embolization of direct carotid cavernous fistulas (DCCFs) has become an optimal treatment. In a few cases, the parent artery has to be sacrificed to achieve morphologic cure. We present our experience with transarterial balloon-assisted n-butyl-2-cyanoacrylate (n-BCA) embolization of DCCFs in which there was failure to achieve angiographic cure and preservation of parent arteries. METHODS: Of 141 patients with traumatic DCCFs who had been treated by transarterial embolization with occlusion of the fistula and parent artery preservation, 18 received transarterial balloon-assisted n-BCA embolization-6 for residual fistula after the balloons detached, 7 for recurrent fistula because of premature balloon deflation or migration, and 5 for repeated puncture of the detachable balloon by the bony fragment at the cavernous sinus. A total of 27 procedures were performed with an average 1.5 attempts per patient, and the volume of the n-BCA mixture varied from 0.5 to 2.3 mL with a mean of 0.83 mL. RESULTS: All DCCFs were successfully occluded by the n-BCA mixture with preservation of parent arteries. One patient with a giant cavernous sinus varix had a fatal subarachnoid hemorrhage. One had a recurrence and was treated by internal carotid artery (ICA) occlusion. Five had asymptomatic pseudoaneurysms at the parent artery. There was no adhesion of the n-BCA mixture to the protective balloon or the microcatheter or n-BCA reflux into the parent arteries. CONCLUSION: Transarterial balloon-assisted n-BCA embolization is a feasible, efficient, and safe treatment for DCCFs when angiographic cure and ICA preservation are not achieved by transarterial detachable balloon embolization.

Brain abscess formation: a delayed complication of carotid blowout syndrome treated by self-expandable stent-graft.

A patient with hypopharyngeal cancer developed carotid blowout syndrome (CBS) treated by self-expandable stent-graft in the left carotid artery. CT scan for progressive right hemiparesis 4 months later showed multiple left cerebral abscesses and left carotid thrombosis. Although deployment of stent-grafts for CBS can achieve initial hemostasis in patients with head-and-neck cancer, the placement of a stent-graft in a field of necrosis and infection is associated with poor long-term outcome. We recommend the use of prophylactic antibiotics if endovascular foreign materials are placed in a contaminated field.

Changes of time-attenuation curve blood flow parameters in patients with and without carotid stenosis.

BACKGROUND AND PURPOSE: From the time-attenuation curves of DSA flow parameters, maximal intensity, maximal slope, and full width at half maximum of selected vascular points are defined. The study explores the reliability of defining the flow parameters by the time-attenuation curves of DSA. MATERIALS AND METHODS: Seventy patients with unilateral carotid artery stenosis (group A) and 56 healthy controls (group B) were retrospectively enrolled. Fixed contrast injection protocols and DSA acquisition parameters were used with all patients. The M1, sigmoid sinus, and internal jugular vein on anteroposterior view DSA and the M2, parietal vein, and superior sagittal sinus on lateral view DSA were chosen as ROI targets for measuring flow parameters. The difference of time of maximal intensity between 2 target points was defined as the circulation time between the target points. RESULTS: The maximal intensity difference of 2 selected points from the ICA to the M1, sigmoid sinus, internal jugular vein, M2, parietal vein, and superior sagittal sinus was significantly longer in group A than in group B. The maximum slope of M1, M2, and the superior sagittal sinus was significantly lower in group A than in group B. The full width at half maximum of M1 and M2 was significantly larger in group A than in group B. The maximal slope of M1 demonstrated the best diagnostic performance. CONCLUSIONS: The maximal intensity difference of 2 selected points derived from DSA can be used as a definitive alternative flow parameter for intracranial circulation time measurement. Maximal slope and full width at half maximum complement the maximal intensity difference of 2 selected points in defining flow characteristics of healthy subjects and patients with carotid stenosis.

Pretreatment diagnosis of suprasellar papillary craniopharyngioma and germ cell tumors of adult patients.

BACKGROUND AND PURPOSE: Suprasellar papillary craniopharyngiomas and germ cell tumors in adults share some clinical and imaging similarities but have different therapeutic strategies and outcomes. This study aimed to evaluate the pretreatment diagnosis of these 2 tumors to improve the therapeutic outcome. MATERIALS AND METHODS: We retrospectively enrolled 18 adults with papillary craniopharyngiomas and 17 with germ cell tumors. The MR imaging findings were evaluated, including signal change and anatomic extension. The medical records were reviewed to collect clinical findings, management, and outcomes. RESULTS: The clinical findings of papillary craniopharyngiomas versus germ cell tumors were as follows: age: 46 ± 13.9 years versus 23 ± 7.1 years (P < .0001); diabetes insipidus: 2/18 (11%) versus 11/17 (65%) (P = .001); recurrence 13/16 (81%) versus 4/17 (24%) (P = .0031). The MR imaging findings of papillary craniopharyngiomas versus germ cell tumors were as follows­pituitary stalk thickening: 1.6 ± 0.4 mm versus 5.4 ± 4.2 mm (P < .0001); vertical infundibular extension: 1/18 (6%) versus 16/17 (94%) (P < .0001); sagittal spheric shape: 17/18 (94%) versus 1/17 (6%) (P < .0001); diffusion restriction: 1/17 (6%) versus 8/12 (67%) (P = .0009). CONCLUSIONS: Younger age, diabetes insipidus, MR imaging characteristics of restricted diffusion, and vertical infundibular extension favor the diagnosis of germ cell tumors. Spheric shape without infundibular infiltration provides clues to papillary craniopharyngiomas, which originate from the pars tuberalis and are located outside the third ventricle. We suggest that suprasellar germ cell tumor is possibly an intraventricular lesion. Appropriate treatment planning can be initiated according to the diagnosis and anatomic location.

Immunohistochemical localization of enkephalin and substance P in the nucleus caudalis of the spinal trigeminal V in the medulla oblongata of the human fetus.

The distribution of enkephalin-positive neurons, substance P-positive and enkephalin-positive fibers was studied in the nucleus caudalis of the trigeminal spinal V in the medulla oblongata regions of developing humans (12 weeks gestation to 40 weeks gestation). Enkephalin-positive neurons were identified in all the subnuclei of the nucleus caudalis as early as 12 weeks of gestation and increased in number as the fetus aged. Substance P-positive neurons were absent in this area throughout development. On the other hand, substance P-positive and enkephalin-positive fibers were present in all the subnuclei, again commencing as early as 12 weeks of gestation. These fibers tended to be linked to each other in the different subnuclei and to the reticular formation in this area and to increase significantly in quantity by the latter quarter of pregnancy. These results show the early presence of these neurons and fibers in the first trimester of development.

Localization of substance P and enkephalin by immunohistochemistry in the spinal cord of human fetus.

The peroxidase-antiperoxidase method was used to study the distribution of substance P and enkephalin during development of the spinal cords of human fetuses. Thirty-seven cases were collected, ranging from 5- to 40-weeks-old (fetal ages). Both types of transmitters were present initially around the fifth week in the mantle layer of the base of the dorsal horn, around the tenth week at the anterior gray and the intermediate gray and around the sixth week at the marginal layer at the base of the ventrolateral funiculus. Substance P- and enkephalin-positive sites at the marginal layers at the base of the dorsolateral funiculus were evident in the same area at 5-6 weeks. The positive fibers in the dorsal horn were initially located in the superficial layers. By the eleventh week, the positive sites spread to other surface layers at the lateral sides of the dorsal horns bilaterally at all spinal levels above the sacral. In the sacral levels adjacent to the conus medullaris, the spreading to surface layers was not apparent bilaterally until the seventeenth week. By weeks 18-26 the positive sites penetrated deeper in the dorsal horn and by week 27 assumed the adult path. The enkephalin cell bodies were present in the Rexed layers I and II of the dorsal horn and the substance P-positive sites were apparent in the dorsal ganglia of the 28-40-week-old fetuses.

Habenulo-interpeduncular descending pathways and their relationship to enkephalin- and somatostatin-immunoreactive neurons in the interpeduncular nucleus of human fetuses.

The interpeduncular nucleus of six human fetuses aged 15 (one specimen), 26 (one specimen), 38 (one specimen) and 40 (three specimens) gestation weeks was studied by immunohistochemistry for enkephalin and somatostatin localization and immunohistochemistry coupled with silver staining. Enkephalin-positive and somatostatin-positive cells were detected, the former initially at 15 weeks gestation and the latter at 26 weeks gestation. They appeared to receive long afferents from the habenular region and projected short efferents to adjacent cells devoid of enkephalin and somatostatin positivity. We postulate that these enkephalin- and somatostatin-positive neurons function as modulatory interneurons in the habenulo-interpeduncular and related pathways.

Distribution of neuropeptide Y in the developing human spinal cord.

The distribution of neuropeptide Y at different levels of the spinal cord of 23 human fetuses aged from 10-41 weeks of gestation was studied using immunocytochemical staining. Neuropeptide Y-immunoreactive neurons were identified at all levels of the spinal cord examined as early as 10 weeks of gestation. These cells were localized in the superficial layers (laminae I and II of Rexed) of the dorsal gray matter. As the age of the fetuses increased, their cell number increased and the region containing positive neurons extended from the superficial to deep layers (laminae III and VI). Immunoreactive fibers started to appear in fetuses at 10 weeks of gestation. They were found not only in the gray and white matters, but also in the pia mater lining the spinal cord. As the fetuses aged, the neuropeptide Y-immunoreactive fibers became mostly concentrated in the intermediate zones of the thoracic and sacral segments corresponding to the developing autonomic centers. Our results suggest that neuropeptide Y may play a role in the early development of the autonomic system.

Acetylcholinesterase-containing neurons, substance P and enkephalin fibers in the ventral horns of developing human embryos and fetuses.

The presence of the acetylcholinesterase neurons and substance P-like and enkephalin-like fibers in the various nuclear columns of the ventral horns of the spinal cords was studied in the developing human by acetylcholinesterase histochemistry and substance P and enkephalin immunohistochemistry. Acetylcholinesterase-positive neurons initially appeared in the lateral neuronal columns and eventually were also observed in the medial columns as well as the median columns at various levels of the spinal cord by 10 weeks' gestation. Acetylcholinesterase-positive neurons in the lower sacral levels were not detected until 11-12 weeks' gestation. Diffused substance P- and enkephalin-like fibers were demonstrated as early as 10 weeks' gestation but did not align with any particular nuclear column until after 15 weeks' gestation. These fibers further increased in length and adopted reticular branching patterns and many of these tended to surround the cell bodies of the nuclear columns. Possible interaction of acetylcholinesterase neurons and substance P and enkephalin fibers would commence by 15 weeks' gestation.

Localization of acetylcholinesterase positive neurons and substance P and enkephalin positive fibers by histochemistry and immunohistochemistry in the sympathetic intermediate zone of the developing human spinal cord.

Localization of acetylcholinesterase positive neurons and substance P and enkephalin fibers were studied by histochemistry and immunohistochemistry in the intermediate sympathetic zone of the spinal cords of 39 human embryos/fetuses from gestation ages five to 40 weeks. Acetylcholinesterase positive neurons were observed in the nucleus intermediolateralis pars principalis as early as the fifth week of gestation. By the ninth to 13th weeks of gestation, positive neurons were also seen in the nuclei intermedialis pars funicularis, intercalatus spinalis and intercalatus pars paraependymalis. Increase in amount of these positive acetylcholinesterase neurons was demonstrated till term. Substance P and enkephalin fibers were initially observed by the eighth gestation week in the intermediolaterlis pars principalis nucleus and positive fibers were then detected in the nucleus intermedialis pars funicularis as well as the nucleus intercalatus spinalis by the 14th week of gestation. By the 26th week of gestation, all the major nuclei intermediolateralis par principalis, intermedialis pars funicularis, intercalatus spinalis and intercalatus pars paraependymalis has substance P and enkephalin fibers. Initial demonstration of acetylcholinesterase positive neurons appeared to be at an earlier stage than that of our substance P and enkephalin positive fibers.

Development and localization of enkephalin and substance P in the nucleus of tractus solitarius in the medulla oblongata of human fetuses.

The presence of enkephalin and substance P-positive neurons and fibers were studied by immunohistochemistry (peroxidase-antiperoxidase or avidin-biotin-peroxidase complex methods) in 26 human fetuses ranging from 11 weeks of gestation to 40 weeks of gestation. Enkephalin-positive neurons were localized in the commissural, medial and intermediate subnuclei as early as 11-12 weeks' gestation. Positive enkephalin fibers were localized around 12 weeks' gestation and in many subnuclei, notably the medial, commissural, intermediate, ventrolateral, ventral and dorsolateral subnuclei. Substance P-positive neurons were localized in the commissural and medial subnuclei around gestation age 13 weeks. Positive substance P fibers appeared even earlier, around 11 weeks of gestation in many subnuclei, notably the medial, intermediate, ventral, ventrolateral and dorsolateral subnuclei. Increase in both enkephalin- and substance P-positive fibers was evident in the later stages of development (e.g. around 26 weeks of gestation). The importance of the early appearance of enkephalin and substance P neurons and fibers of the pain pathways in the major subnuclei connecting with the cardiovascular, gastrointestinal and respiratory functions in the human has to be stressed.