Neurotraumatology: Ultrasonic evaluation of the central nervous system

Abstract

In this study we describe the technique of intraoperative ultrasound imaging of brain and spinal cord in trauma patients. The images are shown and their interpretation is discussed. This intraoperative imaging allows for localization of hematomas, bone fragments and indriven foreign bodies (j.e., pieces of plastic, glass, metal, etc.). DISC matenal and bone fragments deep to the spinal cord can be localized with this technique. Real-time ultrasound can be used to guide instruments within the brain and, thereby, provide dynamic guidance for removal of bone fragments and foreign bodies dynamically. In summary, Intraoperative real-time ultrasonic Imaging is of use to the neurosurgeon in the treatment of the neurotrauma patient. [Neural Res 1997; 19: 317–322]

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Asymmetrical regional changes in energy metabolism of the central nervous system during walking

Cats were injected with 2-deoxy-[¹⁴C]glucose (2-DG) while walking on a moving treadmill (experimental group), or sitting down on a stationary one (controls). After a 45-min equilibration period they were anesthetized, and their central nervous system (CNS) was removed rapidly and frozen. The tissue blocks were sectioned serially, and X-ray film exposed to the sections was used for quantitative densitometric analysis by Sokoloff's method. The utilization of glucose in a CNS region (LCMRg) was regarded as a measure of that region's energy metabolic activity and — indirectly — of its functional status. The walking cats exhibited significantly higher LCMRg in many but not all places of the neuraxis, compared to the control group. Also, LCMRg was symmetrical (side to side) in the control group but significantly asymmetrical in certain regions of the CNS in the experimental group. In all but one of these cats the LCMRg was greater in the right side of the gray matter of the cervical spinal cord and in the left visual and motor cortices and caudate nucleus. The finding that the motor cortex and other supraspinal regions become more active during walking suggests they may contribute to the control of locomotion and/or processing of related sensory data. The side to side assymetry in the spinal cord and hemispheres during walking may be related to the phenomenon of lateral dominance.     

Immunohistochemical localization of connective tissue growth factor in the rat central nervous system

Connective tissue growth factor (CTGF) is an immediate early growth-responsive gene but its distribution and significance in the central nervous system (CNS) are unknown. We investigated the distribution of CTGF-like immunoreactivity (CTGF-IR) in the rat CNS using a specific antiserum against CTGF oligopeptide. The majority of CTGF-IR was observed in astrocytes. Ependymal cells lining the wall of the cerebral ventricle and tanycytes lining the central canal of the spinal cord showed the strongest CTGF-IR, while there was a diffuse but weak signal in the gray matter of the spinal cord. CTGF-IR was also detected in the cytoplasm of a subpopulation of pyramidal neurons in the cerebral cortex. Our results showed that CTGF-IR is widely distributed in the CNS at both regional and cellular levels, suggesting a complex functional role in the CNS.     

Primary central nervous system sarcomas in children: clinical,radiological, and pathological features

Patients and methods The clinical, radiological, surgical, and pathological findings of 16 children with a primary central nervous system (CNS) sarcoma are reported. There were 8 (50%) girls and 8 (50%) boys ranging in age from 4 months to 14 years (mean age 4.8 years). Four patients (23%) were in their 1st year of life. Fourteen children (87%) had an intracranial sarcoma, and 2 (13%) had intraspinal tumors. Nine intracranial tumors (60%) were supratentorial. The parietal and temporal regions were the most frequently involved sites.Results Characteristic imaging findings included tumor cysts in 7 patients and marked tumoral enhancement in 9 (69%) with intratumoral calcification and hemorrhage. All patients underwent at least one operation to surgically remove the tumor with the aim of maximal resection and 3 patients underwent a second resection due to a recurrent tumor. Resection was total in 9 (53%) patients and subtotal in another 7 (41%). Dural attachment by tumor was confirmed in 7 (44%) patients and parenchymal invasion was present in 9 (56%). In one-third of the patients there was a well-defined plane of dissection around the tumor. Postoperative radiation was used in 10 patients. Postoperative chemotherapy was used in all but 2 patients. Immunohistochemical studies were available in 13 patients with the most consistent finding being strong vimentin positivity. Five out of the 6 patients in whom the proliferation markers were obtained demonstrated a high proliferation index (Ki-67 labeling index, 20–50%). The mean length of survival in the group was 4.6 years (range 1 month to 16 years). Children who presented in the 1st year of life had shorter survival than those who presented at an older age. Six patients (40%) had cerebrospinal fluid (CSF) dissemination of the tumor. CSF dissemination was associated with a shorter mean survival of 1.9 years.Conclusions Our review of this series of patients indicates the requirement for adjuvant therapy and for continued efforts to classify tumor subtypes aimed at optimizing future treatments for patients with a primary CNS sarcoma.An erratum to this article can be found at     

Historadioautographic localisation of oxytocin and vasopressin binding sites in the central nervous system of the merione (Meriones shawi)

The distribution of vasopressin and oxytocin binding sites in the central nervous system of the merione (Meriones shawi), a rodent adapted to desert life, was studied by means of conventional film radioautography at macroscopic scale and historadioautography at cellular level using radioiodinated ligands highly selective for either oxytocin or type V1 a vasopressin receptors. Both types of binding sites exhibited the same selectivity for endogenous peptides as in the rat. Distribution of oxytocin binding sites was similar in some structures (limbic system, spinal cord) to that described in the rat and in other rodents. Vasopressin binding sites were much more widely distributed in the merione than in the rat brain. In addition to locations common to most rodents (lateral septum and suprachiasmatic nucleus), in merione vasopressin binding sites occurred in several areas known to express oxytocin binding sites in the rat (olfactory system, hypothalamus). Colocalisation of vasopressin and oxytocin binding sites, which occurred in the CA1 and CA2 fields of Ammon's horns of the hippocampus, the caudate-putamen and the fundus striati of the merione, has so far not been reported in any other rodent.     

Capillary hemangioma of the central nervous system: a comparative study with lobular capillary hemangioma of the skin

Capillary hemangiomas have rarely been reported to develop in the brain or spinal cord. Here we report the histological and immunohistochemical features of ten cases of central nervous system capillary hemangiomas (CNSCH) and compare these to those of lobular capillary hemangioma (LCH) of the skin. CNSCH showed a lobular architecture with lobules that were separated by fibrous tissue septa in six cases. The lobules were composed of numerous, tightly packed, capillary-sized vessels. A highly cellular area was seen in six cases. A blood-filled cavernous space and fibroendothelial papillae that mimicked papillary endothelial hyperplasia were seen in four cases. Stromal edema was observed in nine cases. These features were not statistically different from those of LCH of the skin, although the highly cellular area was more prominent and more frequent in cases of CNSCH. Immunohistochemical studies demonstrated no positive staining of endothelial cells within either lesion for erythrocyte-type glucose transporter protein, which is a selective marker for capillary hemangioma of infancy. Vascular endothelial growth factor immunostaining demonstrated positive cells in the solid or immature-appearing areas without vessel lumen formation in both lesions. Some of the endothelial cells and stromal cells were positive for glucocorticoid receptor immunostaining. The MIB-1 index of CNSCH was variable (mean 5.6%) and the apoptotic index of CNSCH was significantly lower than that of LCH of the skin. CNSCH are benign lesions with histological and immunohistochemical features similar to those of LCH of the skin.     

Primary rhabdomyosarcoma of the central nervous system

Summary A case of primary rhabdomyosarcoma in the brain stem is described in an 8 year old girl. The clinical data showed a right side hemiplegia then a total paralysis of the left sixth cranial nerve and a paraplegia which became lethal in 3 months. The necrospy revealed a tumoral nodule in the left medulla oblongata and pons with diffuse subarachnoidal extension from the cranial nerves to the cauda equine roots. Histologically the tumor appeared to be polymorph with numerous rhabdomyoblasts which had a clear cross striation and which were sometimes less differentiated without any neuronal or glial elements. Perivascular tumoral cells and blood vessels were closely linked, the Virchow-Robin spaces were clearly involved. The electron microscopic study confirmed that the less differentiated cells were of a rhabdomyoblastic nature. A review of the litterature indicates that these malignant neoplasias are highly exceptional, and can be classified within the group of primary tumors of the neuraxis with muscular elements. The histogenetic origin of these tumors appears to be the ectomesenchyme of neural creats.Our special thanks to Miss Chantal Mariotte who took care of the translation.Department of Neurology (Pr. Ag. J. Perret)     

Rhabdoid tumors of the central nervous system

Rhabdoid tumors of the central nervous system are rare malignancies with a still almost uniformly fatal outcome. There is still no proven curative therapy available. We report our experience with nine patients with central nervous system rhabdoid tumors. Gross complete surgical removal of the tumor was achieved in six patients. Seven patients received intensive chemotherapy. Four of these were treated in addition with both neuroaxis radiotherapy and a local boost directed to the tumor region, while two patients received local radiotherapy only. The therapy was reasonably well tolerated in most cases. Despite the aggressive therapy, eight of the nine patients died from progressive tumor disease, and one patient died from hemorrhagic brain stem lesions of unknown etiology. The mean survival time was 10 months after diagnosis. Conventional treatment, although aggressive, cannot change the fatal prognosis of central nervous system rhabdoid tumors. As these neoplasms are so rare, a coordinated register would probably be a good idea, offering a means of learning more about the tumor’s biology and possible strategies of treatment. Received: 7 September 1999     

中枢神经系统原发性套细胞淋巴瘤

目的报告1例中枢神经系统原发性套细胞淋巴瘤患者的临床、病理以及影像学表现．以提高对该病的认识。方法回顾性分析患者临床表现、影像学特征、细胞学与组织病理学表现以及治疗情况，并对脑脊液细胞和异常脑组织进行免疫组织化学染色和基因重排检测。结果临床主要表现为阵发性头晕、渐进性加重的行走不稳伴恶心、呕吐。头部MRI检查脑实质呈多发异常信号．无强化和占位效应。脑脊液细胞学检查呈现小至中等大小的淋巴细胞，细胞核形态欠规则，可见核分裂象：组织病理学显示胶质纤维背景中散在分布有淋巴细胞，可见血管周聚集现象及软脑膜浸润，肿瘤细胞染色质深染，少部分细胞可见小核仁，核分裂象少见；肿瘤细胞表达CD20、CD5及细胞周期素D1等标志物。基因重排检测免疫球蛋白重链呈单克隆性。采用以大剂量甲氨蝶呤为主的化疗方案，同时神经鞘内注射利妥昔单抗注射液，治疗2d后患者出现昏迷，因家属拒绝抢救而出院。结论中枢神经系统原发性套细胞淋巴瘤为临床罕见淋巴瘤，其组织学表现与发生在颅外组织者不同，影像学表现亦有别于其他类型的中枢神经系统原发性淋巴瘤，临床治疗方案尚有待进一步探讨。     

Regional distribution of nitric oxide synthase and NADPH-diaphorase activities in the central nervous system of teleosts

Neuronal nitric oxide synthase (nNOS) and NADPH-diaphorase activities were investigated in discrete areas of the central nervous system of goldfish and brown trout. Both species showed a similar distribution pattern of nNOS activity with regional differences in all examined areas. Telencephalon and hypothalamus showed the highest nNOS values, while in the goldfish cerebellum and its valvula nNOS was not detectable. In both species, NADPH-diaphorase activity showed a lower regional variability, compared to nNOS. The highest activity was measured in the olfactory bulbs where, conversely, low levels of nNOS activity were present. The non close correspondence between NOS and NADPH-diaphorase activities confirms the discrepancies indicated by morphological data. Western blot analysis revealed the presence of a nNOS isoform of about 150 kDa mol. wt. corresponding to that of mammals. The pattern of nNOS expression in the considered brain regions of the goldfish and trout was comparable to the levels of the nNOS activity.     

Hyperammonemia-induced toxicity for the developing central nervous system

In pediatric patients, hyperammonemia can be caused by various acquired or inherited disorders such as urea cycle deficiencies or organic acidemias. The brain is much more susceptible to the deleterious effects of ammonium during development than in adulthood. Hyperammonemia can provoke irreversible damages to the developing central nervous system that lead to cortical atrophy, ventricular enlargement and demyelination, responsible for cognitive impairment, seizures and cerebral palsy. Until recently, the mechanisms leading to these irreversible cerebral damages were poorly understood. Using experimental models allowing the analysis of the neurotoxic effects of ammonium on the developing brain, these last years have seen the emergence of new clues showing that ammonium exposure alters several amino acid pathways and neurotransmitter systems, as well as cerebral energy metabolism, nitric oxide synthesis, oxidative stress, mitochondrial permeability transition and signal transduction pathways. Those alterations may explain neuronal loss and impairment of axonal and dendritic growth observed in the different models of congenital hyperammonemia. Some neuroprotective strategies such as the potential use of NMDA receptor antagonists, nitric oxide inhibitors, creatine and acetyl-l-carnitine have been suggested to counteract these toxic effects. Unraveling the molecular mechanisms involved in the chain of events leading to neuronal dysfunction under hyperammonemia may be useful to develop new potential strategies for neuroprotection.     

Primary Hodgkin lymphoma of the central nervous system

Primary involvement of the central nervous system by Hodgkin lymphoma is rare; most cases represent metastases. We report a primary Hodgkin lymphoma presenting in the cerebellum of a 77-year-old man and review the literature on primary Hodgkin lymphoma of the central nervous system.     

Distribution of trkB tyrosine kinase immunoreactivity in the rat central nervous system

Recent evidence suggests thattrkB tyrosine kinase is a high affinity receptor for brain-derived neurotrophic factor (BDNF). BDNF can act as a survival factor for several neuronal subgroups and its mRNA is distributed widely throughout the central nervous system. However, the functional targets of BDNF are poorly defined. We have used immunochemical and immunohistochemical techniques to determine·the regional distribution and cellular localization oftrkB tyrosine kinase-like immunoreactivity. The staining pattern indicates that thetrkB-like antigen is widely distributed and present within both glia and neurons. Astrocytes were the most intensively labelled but many neuronal populations were also stained. In some regions including brain stem, spinal cord, hippocampus and diagonal band of Broca, neurons were stained at varying intensities. In other areas such as the cortex of the forebrain and amydaloid nucleus, the stain was intense but diffuse, preventing positive identification of the cell types involved. Immunoblot results indicated two separate protein bands in all brain and spinal cord regions examined, of molecular weights 145 and 85 kDa, respectively. These findings aid the definition of neuronal and glial subpopulations of the central nervous system that may utilize BDNF.     

Superficial siderosis of the central nervous system secondary to spinal ependymoma

Superficial siderosis of the central nervous system is a syndrome caused by deposition of hemosiderin in the subpial layers of the central nervous system, occurring as a result of recurrent asymptomatic or symptomatic bleeding into the subarachnoid space. We report a rare case of superficial siderosis in a 33-year-old man who presented with sensorineural hearing loss. The diagnosis of superficial siderosis on MRI brain studies led to further investigations with detection of a spinal ependymoma at L1–L2, compressing the cauda equina. Gross total resection of the tumor arrested the progression of the neurological deterioration. Our report underlies the importance of early diagnosis and surgical management, with imaging examination of the full neuroaxis to identify the source of bleeding, to halt disease progression and improve prognosis.     

Chemotherapy of central nervous system tumours in infants

The development of curative strategies for infants and children with central nervous system tumours or acute lymphoblastic leukaemia involve similar clinical research principles. Both areas of paediatric oncology research focus on cancers with a broad range of sensitivity to chemotherapy and radiation therapy, together with concerns about the neurodevelopmental, neuroendocrine and growth outcomes of survivors. These considerations have influenced the design of curative- intent treatments, strategies for successfully eradicating leptomeningeal disease, and the importance of anatomic and functional identification of residual disease. Unlike the situation with childhood leukaemia, the emotional barriers of pessimism or even nihilism previously evident towards infants with brain tumours have only begun to crumble during the past decade. The challenge to improve both the quality and overall survival of infants with CNS tumours described in this chapter is ours to meet as we move into the new millennium. This paper examines the development of ’infant’ approaches to the treatment of CNS tumours, including a discussion of epidemiology, the reasons for avoiding or delaying radiation therapy, and traces the chemotherapy hypotheses tested over the past two decades in the process of developing potentially curative therapy. The reasons for the disappointing rate of progress compared with that in childhood leukaemia, despite similar clinical research paradigms, are discussed, and potential opportunities are identified. Received: 12 April 1999     

Calcium pumps in the central nervous system

Two families of Ca²⁺ transport ATPases are involved in the maintenance of Ca²⁺ homeostasis in the nervous system, the plasma membrane Ca²⁺-ATPase that pumps Ca²⁺ to the extracellular medium and the intracellular sarco/endoplasmic reticulum Ca²⁺-ATPase that transports Ca²⁺ from the cytosol to the endoplasmic reticulum. Both types of calcium pumps show precise regulatory properties and they are localized in specific subcellular regions. In this review, we describe the functional and regulatory properties of both families of calcium pumps, their distribution in nerve cells, and their involvement in neurological disorders. The functional characterization of neuronal calcium pumps is very important in order to understand the biochemical processes involved in the maintenance of intracellular calcium in synaptic terminals.     

Phenothiazines reduce ischemic damage to the central nervous system

We found substantial alterations in reactions catalyzed by calcium/phospholipid-dependent and calcium/calmodulin-dependent protein kinases during CNS ischemia which suggested that phenothiazines, drugs capable of inhibiting these reactions, might reduce neurologic damage. To test this hypothesis, we used chlorpromazine and trifluoperazine. Both drugs reduced neurologic function deficits relative to controls in a rabbit multiple cerebral embolism model and a rabbit spinal cord ischemia model. Chlorpromazine was effective despite reduction of blood pressure, and trifluoperazine did not alter blood pressure. These findings suggest that phenothiazines may be useful for preserving neurologic function when administered shortly after the onset of CNS ischemia.     

Primary central nervous system gamma delta cytotoxic T-cell lymphoma

Primary T-cell lymphomas of the central nervous system (CNS) are uncommon, but aggressive and increasing in incidence. We describe a rare case of T-cell lymphoma in a cerebellar location, to our knowledge the first reported case demonstrating gamma/delta receptor expression. Additionally, we elaborate on key diagnostic features and review all nine patients with primary CNS lymphoma of cytotoxic T-cell phenotype reported in the literature. A 26-year-old female medical student presented with a 6 week history of nausea, vomiting and dizziness. MRI revealed a 2 cm cerebellar mass. The tumor was subtotally resected, and pathologic examination of a subtotal resection specimen demonstrated peripheral T-cell lymphoma, not otherwise specified, with a gamma/delta cytotoxic T-cell phenotype. She subsequently started high dose methotrexate and cytarabine. We report a unique case of primary CNS gamma delta CD8+ T-cell lymphoma lineage in a young female patient. While these are rare entities, it is an important differential diagnosis to consider. Therapy should be tailored to the patient, and involves resection with adjuvant chemotherapy, radiotherapy or autologous stem-cell based treatments.     

Elevated CSF lactoferrin in superficial siderosis of the central nervous system

This study sought to identify abnormalities in the levels of iron transport proteins in patients with superficial siderosis of the central nervous system. We compared patients with superficial siderosis (n = 7) with patients suffering from various other neurological disorders (n = 176, total). CSF and serum levels of lactoferrin, and CSF levels of transferrin were measured by enzyme-linked immunosorbent assay. Serum transferrin was measured by nephelometry. Lactoferrin, but not transferrin, levels in the CSF were significantly elevated in superficial siderosis. Unexpectedly, CSF transferrin was decreased in multiple sclerosis patients. Enhanced CSF lactoferrin may reflect an increased iron transport requirement in the central nervous system in superficial siderosis and might be a useful measure for monitoring response to therapy. Received: 5 January 1999 Received in revised form: 30 March 1999 Accepted: 5 May 1999