[Clinical forms and prognostic factors of chronic subdural hematoma in the adult]. / Formes cliniques et facteurs pronostiques de l'hématome sous-dural chronique de l'adulte.

The most common clinical signs for chronic subdural hematoma in adults are: motor weakness, increased intracranial pressure, confusion and loss of consciousness. This pathology is more frequent in the elderly over 65 years, the diagnosis also being more difficult in this case. Some misleading clinical presentations may delay the decision to perform a CT scan to assess the diagnosis. Preoperative headaches and isodensity in CT-scan are features of good prognosis. Chronic alcoholism and postoperative pneumocephalus are related with poor prognosis.

[Complications of chronic subdural hematoma in the adult]. / Les complications de l'hématome sous-dural chronique de l'adulte.

Chronic subdural hematoma is subject to post-operative fatal and non-fatal complications in 5 to 10% of the cases. Mortality ranges from 0 to 8%, depending on the preoperative clinical status. There is an average recurrence in 8% of the cases, chiefly linked to the absence of drainage. Empyema occurs in 2% of patients, especially when the drain is left in place more than 3 days. In most of the series, long-term epilepsy is a rare complication and patients do not require antiepileptic drugs. The lack of cortical reexpansion, postoperative intracerebral hematoma and tension hydrocephalus are, among others, complications occurring after surgery. Finally, 10% of the patients will have a permanent neurological impairment.

Effects of spinal cord X-irradiation on the recovery of paraplegic rats.

Axonal regrowth is limited in the adult CNS, especially in the spinal cord, one of the major sites of traumatic lesions. Pathophysiological changes occurring after spinal cord injury include complex acute, subacute, and late processes. In this study, we assessed whether X-irradiation interferes with the acute/subacute phases, thereby improving the functional recovery of paraplegic animals. Two days after acute compression of adult rat spinal cords, various doses (0, 2, 5, 10, 20 Gy) of X-rays were administered as one single dose to the compression site. The animals were functionally evaluated over the course of 1 month after injury, using the Tarlov scale and the Rivlin and Tator scale. We also designed a "physiological" scale, including an assessment of urinary function and infection, appropriate for the evaluation of spinal-cord-lesioned animals. Behavioral analysis suggested that the high doses, 20 Gy and, to a lesser extent, 5 and 10 Gy, were toxic, as shown by morbidity rate and "physiological" score. The 2-Gy group showed better motor performances than the lesioned nonirradiated (LNI) animals and the 5- and 20-Gy groups. Motor performance in the 5-, 10-, and 20-Gy groups was poorer than that seen in the LNI group. Gliosis was reduced in the 2-Gy group compared to LNI animals, and there was high levels of gliosis in the highly (>/=5 Gy) irradiated animals. There was a 23% less lesion-induced syringomyelia in the 2-Gy group than in the other groups (LNI and 5-20 Gy). Thus, low doses of X-rays may interfere with the formation of syringomyelia and glial scar, thereby facilitating the recovery of paraplegic animals. These findings suggest that low-dose irradiation of the lesion site, in association with other therapies, is a potentially promising treatment for improving recovery after spinal cord injury.

Toward autologous ex vivo gene therapy for the central nervous system with human adult astrocytes.

The combination of gene transfer techniques and cell transplantation is a promising approach to deliver therapeutic molecules into the CNS. To optimize gene transfer systems, several neural and nonneural cell types are currently under investigation. Among these cells, astrocytes are particularly well suited because of their CNS origin, their efficient secretory mechanisms, and their role as neuronal support. Most importantly, the use of human adult astrocytes as cellular vehicles for ex vivo gene transfer may open the way to autologous transplantation, thus obviating immunological rejection and the side effects of immunosuppressors. In the present study, we report the ability of these cells to be expanded and genetically modified in vitro. Astrocytes derived from human adult cerebral cortex were grown and maintained in vitro as pure primary cultures for at least 10 months. In addition, cells were efficiently transduced by an adenoviral vector encoding human tyrosine hydroxylase (hTH) under the negative control of the tetracycline-based regulatory system (tet-off). The infected cells synthesized large amounts of active hTH and released L-dopa. In addition, doxycycline, a potent analog of tetracycline, efficiently regulated transgene expression. This work is a first step toward the development of therapeutic strategies based on the use of genetically engineered human adult astrocytes for autologous transplantation in human neurodegenerative diseases and CNS trauma.

Benign cerebellar astrocytomas in children.

OBJECT: Cerebellar astrocytomas are benign tumors of childhood known to be associated with excellent long-term survival in patients in whom complete surgical resection is possible. However, the roles of other factors--clinical, radiological, histological, and therapeutic--in the survival of the patient, tumor recurrence, and long-term patient outcome remain imprecise. The goal of this study was to examine these factors and their relationships. METHODS: To clarify these issues a retrospective review was conducted of 168 children who were surgically treated for a cerebellar astrocytoma at Hôpital Necker-Enfants Malades between 1955 and 1995. These patients' clinical files were examined, the histological characteristics of their tumors were reviewed, and their outcomes were assessed according to Bloom's scale and the Wechsler intelligence quotient test. Of the 168 patients in the study, 91 were male and 77 were female with a mean age of 6.9 years and a mean follow up lasting 7.7 years. Tumors were identified as being strictly located in the cerebellum in 76.2% of the patients and as involving the brainstem (referred to as the "transitional form") in 23.8% of the patients. Complete surgical excision was possible in 88.7% of cases. There was a total mortality rate of 4.2% and a tumor recurrence rate of 9.5%. Fifty-eight percent of the patients had no neurological sequelae at follow-up evaluation. Pejorative factors that were discovered by multivariate analysis to be important included: a long preoperative duration of symptoms and the transitional form of tumor with respect to survival; incomplete tumor excision with respect to an increased risk of recurrence; and a long preoperative duration of symptoms, an early epoch during which surgery was performed (1955-1974), severe ventricular dilation, and the transitional form of tumor with respect to a poorer long-term patient outcome. CONCLUSIONS: The presence of brainstem involvement (tumor in the transitional form) emerged as a significant negative prognostic factor and should be treated as a distinct nosological entity. The extent of surgical excision has a significant bearing on the risk of tumor recurrence.

Papillomas and carcinomas of the choroid plexus in children.

OBJECT: Choroid plexus tumors are rare intraventricular tumors (1% of all intracranial tumors) that occur mainly in children. The pathophysiological characteristics of associated hydrocephalus, surgical management, and oncological issues related to these tumors remain a matter of debate. To understand more about these tumors, the authors have reviewed their experience with the management of 38 children with choroid plexus tumors. METHODS: There were 25 cases of papilloma and 13 of carcinoma. The mean age of the patients at presentation was 22.5 months, and one-half of the patients were younger than 2 years of age. Hydrocephalus was present in 33 patients and poorly correlated with the size, site, and pathological characteristics of the tumor. In nine children, a ventriculoperitoneal shunt was required after tumor excision, calling into question the notion that cerebrospinal fluid oversecretion is the only cause of hydrocephalus. Complete excision was achieved in 96% of the cases of papilloma and 61.5% of the cases of carcinoma. These surgical procedures were complicated by the risks of intraoperative hemorrhage, which proved to be fatal in two cases, and postoperative brain collapse, which led to subdural fluid collections requiring subdural shunt placement in six patients. Preoperative embolization was partially successful in four cases and significantly assisted surgery. Preoperative controlled drainage of excessively dilated ventricles and intraoperative gluing of the cortical incision have been used to address the problem of postoperative brain collapse. Patients with carcinomas were treated postoperatively by chemotherapy alone (seven cases), radiotherapy (one case), or chemotherapy plus radiotherapy (one case). The overall 5-year survival rate was 100% for patients with papillomas and 40% for those with carcinomas. CONCLUSIONS: Total surgical excision is curative in cases of papillomas. For carcinomas, the most effective treatment remains total surgical excision; however, adjuvant treatment in the form of chemotherapy in patients younger than age 3 years, supplemented by radiation therapy in older children, can moderately reduce the risk of recurrence.

[Experimental medullary lesions: prevention of the extension of secondary lesions and formation of glial scarring]. / Lésions médullaires expérimentales: prévention de l'extension des lésions secondaires et de la formation des cicatrices gliales.

Early treatment of spinal cord lesions is undertaken following two lines of research carried in adult rats: First, the reduction of secondary lesions, immediately after the trauma, second, the prevention of glial scar formation in the following days. In the first case, after a photochemical focal lesion at thoracic level (T8), a specific, non competitive antagonist of NMDA, TCP, is injected systemically. The result is the reduction of the extent of the lesion, as measured in serial coronal sections, the improvement of the performance in two functional tests of hindlimb function, and the improvement of somatosensory evoked potentials. In the second case, the spinal cord of rats were hemisected at thoracic level (T8-T9), and a suspension of liposomes containing a cholesterol derivative (7 beta-OH cholesteryl-oleate) was administered through a sub dural catheter, 2 days after the section. Histological investigations evidenced a reduction of astrocyte hyperplasia and hypertrophy, together with the blocking of the expression of a cell adhesion molecule, the so-called polysialic N-CAM. This resulted, within 5 weeks after the lesion, in the growth of axons in the denervated dorsal horn, below hemisection originating from the contralateral side. In conclusion, these two experimental studies constitute the basis for a coherent strategy of treatment in spinal cord traumatic lesions. Their sequential application could even improve the functional outcome of spinal cord lesions. However, these two research lines do not exclude other associated treatments such as the local applications of growth factors, which can potentiate both neuron survival and axonal sprouting.

Thienylphencyclidine protection for the spinal cord of adult rats against extension of lesions secondary to a photochemical injury.

The purpose of this study was to evaluate treatment with the N-methyl-D-aspartate antagonist thienyl-phencyclidine (TCP) after spinal cord injury for its behavioral, electrophysiological, morphological, and immunohistochemical effects. Five minutes after a photochemical lesion was produced in rats at the T-8 level, the animals received TCP (1 mg/kg, intravenously) or TCP vehicle (saline). The animals were evaluated on Day 18 for neurological recovery by testing motor and sensory functions. The TCP-treated group showed less neurological impairment than the untreated group (p < 0.05 for inclined-plane stability and withdrawal reflex to extension). Somatosensory evoked potential testing was performed on Days 21 to 23 and the wave amplitude between the onset and P1 in the TCP-treated group was higher than in the untreated group (p < 0.05). Mean arterial blood pressure was not significantly modified after TCP injection. Morphometric studies of the lesion area in cross section revealed a significantly reduced spinal cord infarction in the TCP-treated group (p < 0.05). Immunohistochemical evaluation of the spinal cord in lumbar area showed an increased level of serotonin immunoreactivity in the dorsal horn of animals treated by TCP. These results demonstrate the efficacy of TCP in reducing secondary lesions after spinal cord injury in rats.

[Spinal cord injuries: comments on preventive and curative strategy]. / Lésions médullaires traumatiques: réflexions sur une stratégie préventive et curative.

Research for the cure for paralysis caused by spinal cord injury has followed three complementary lines: Limitation of secondary lesions; the use of antagonists of excitatory amino acids has proven affective in reducing the extent of the lesions. Control of the glial scar; an oxygenated derivative of cholesterol can reduce the proliferation of reactive astrocytes and their hypertrophy, and permit the regrowth of axons in a denervated territory. Transplantation of embryonic neurons below the lesion allows to reinnervate denervated sites and reestablish reflex functions.