Renewing the fire: Joseph Babinski.

Joseph Babinski (1857-1932), a French neurologist of Polish origin, was a physician of the Paris hospitals and member of the Academy of Medicine. Two main periods must be distinguished in his scientific activity. Early in his career, Babinski, working as an anatomo-pathologist and his tologist under the direction of Victor Cornil, Alfred Vulpian and Louis Ranvier, reported on several observations of general pathology and neuropathology. After his chief residency under Charcot (from 1885 to 1887), Babinski abandoned his previous interests and became increasingly involved with hysteria. He thus became a semiologist, eager to detect objective neurological signs that would allow the clinician to distinguish between organic (due to a lesion) and functional (hysterical) illnesses. He is well-known for the discovery of the sign (the toes phenomenon) which bears his name. Beyond the sign, his semiological work in the field of neurology is also important (particularly cutaneous and osteotendinous reflexes, cer-ebellar and vestibular semiology, hysteria and pithiatism, physiopathic disorders and also syphilis of the nervous system, tabes, pupillar reflex). Several other signs and syndromes bear his name. Unlike Charcot and the majority of his fellow neurologists, Babinski was deeply committed to therapeutics. He had a determinant role in the birth of the French neurosurgery, especially in guiding Thierry de Martel and Clovis Vincent in their choice of career. The personality of Joseph Babinski is complex. He was addicted to work, extremely scrupulous and a perfectionist. With his beloved brother Henri, who wrote Gastronomie pratique under the pen name Ali-Bab, he had formed an exceptional team, within which each contributed to the other's professional interests.

Comparative genetic analysis of quantitative traits in sunflower (Helianthus annuus L.). 2. Characterisation of QTL involved in developmental and agronomic traits.

Seed weight and oil content are important properties of cultivated sunflower under complex genetic and environmental control, and associated with morphological and developmental characteristics such as plant height or flowering dates. Using a genetic map with 290 markers for a cross between two inbred sunflower lines and 2 years of observations on F3 families, QTL controlling seed weight, oil content, plant height, plant lodging, flowering dates, maturity dates and delay from flowering to maturity were detected. QTL detected were compared between the F2 and F3 generations and between the 2 years of testing for the F3 families in 1997 and 1999. Some of the QTL controlling seed weight overlapped with those controlling oil content. Several other co-localisations of QTL controlling developmental or morphological characteristics were observed and the relationships between the traits were also shown by correlation analyses. The relationships between all these traits and with resistance to Sclerotinia sclerotiorum and Diaporthe helianthi are discussed.

Identification of non-TIR-NBS-LRR markers linked to the Pl5/ Pl8 locus for resistance to downy mildew in sunflower.

The resistance of sunflower, Helianthus annuus L., to downy mildew, caused by Plasmopara halstedii, is conferred by major genes denoted by Pl. Using degenerate and specific primers, 16 different resistance gene analogs (RGAs) have been cloned and sequenced. Sequence comparison and Southern-blot analysis distinguished six classes of RGA. Two of these classes correspond to TIR-NBS-LRR sequences while the remaining four classes correspond to the non-TIR-NBS-LRR type of resistance genes. The genetic mapping of these RGAs on two segregating F2 populations showed that the non-TIR-NBS-LRR RGAs are clustered and linked to the Pl5/ Pl8 locus for resistance to downy mildew in sunflower. These and other results indicate that different Pl loci conferring resistance to the same pathogen races may contain different sequences.

Long-term survival after gene therapy for a recurrent glioblastoma.

A patient presenting with a recurrent glioblastoma (GBM) survived 3 years after suicide gene therapy and finally died of a disseminated breast cancer with no indication of tumor recurrence on MRI. Postmortem analysis showed no evidence of recurrence of the GBM, neither near the initial tumor localization nor in any other area of the brain. Such an evolution is unusual in the course of this disease and may suggest in this particular case a cure of the GBM.

[Diabetes insipidus after endoscopic third ventriculostomy. A case report and review of the literature]. / Diabète insipide après ventriculocisternostomie par voie endoscopique. A propos d'un cas et revue de la littérature.

Endoscopic third ventriculostomy has been found to be successful for treating occlusive hydrocephalus. The complication rate ranges from 6 to 12%. Intraoperative bleeding is the most common incident. Endocrinological failures are rare, mainly due to the proximity of the hypothalamic structures. We report the case of a 33-year-old man who was referred in emergency for subacute hydrocephalus related to a tentorium meningioma. The hydrocephalus was treated by endoscopic third ventriculostomy. During the procedure, the floor of the third ventricle was found to be thick but fenestration was performed without incident. After surgery, the clinical signs of hydrocephalus disappeared but diabetes insipidus was diagnosed the same day. There were no other endocrinology disorders. Medical treatment with vasopressin allowed resolution of the diabetes insipidus in fifteen days. Surgical debulking of the meningioma was then achieved via a subtemporal approach. There was no recurrence of the endocrinology disorder. Diabetes insipidus is an unpredictable complication of third ventriculostomy. The mechanism is not well known. It is however a transient disorder that can easily be treated with vasopresin and therefore should not modify the indications of third ventriculostomy, especially in tumor-related hydrocephalus.

Obstruction of Magendie's and Luschka's foramina. Cine-MRI, aetiology and pathogenesis.

BACKGROUND: Obstruction of the foramina of Magendie and Luschka represents one possible aetiology for a progressive tetra-ventricular hydrocephalus. METHOD: Our case report is a 58-year-old woman initially presenting with a pseudo-vertebrobasilar insufficiency clinical syndrome. A ventriculo-cisternostomy of the third ventricle was performed by an endoscopic procedure with a clinical and radiological success (three year follow-up). FINDINGS: Comparative studies of cerebrospinal fluid (CSF) flow measurements by cine magnetic resonance imaging (cine-MRI) showed that Magendie's and Luschka's foramina permeabilities were restored after the ventriculo-cisternostomy. INRTERPRETATION: This case shows that endoscopic ventriculo-cisternostomy of the third ventricle can provide an effective treatment for specific tetra-ventricular hydrocephalus. Cine-MRI findings open the discussion on possible aetiologies and pathophysiologies.

Radiosurgery for re-irradiation of brain metastasis: results in 54 patients.

PURPOSE: To evaluate in terms of probabilities of local-regional control and survival, as well as of treatment-related toxicity, results of radiosurgery for brain metastasis arising in previously irradiated territory. PATIENTS AND METHODS: Between January 1994 and March 2000, 54 consecutive patients presenting with 97 metastases relapsing after whole brain radiotherapy (WBRT) were treated with stereotactic radiotherapy. Median interval between the end of WBRT and radiosurgery was 9 months (range 2-70). Median age was 53 years (24-80), and median Karnofski performance status (KPS) 70 (60-100). Forty-seven patients had one radiosurgery, five had two and two had three. Median metastasis diameter and volume were 21 mm (6-59) and 1.2 cc (0.1-95.2), respectively. A Leksell stereotactic head frame (Leksell Model G, Elektra, Instrument, Tucker, GA) was applied under local anesthesia. Irradiation was delivered by a gantry mounted linear accelerator (linacs) (Saturne, General Electric). Median minimal dose delivered to the gross disease was 16.2 Gy (11.8-23), and median maximal dose 21.2 Gy (14- 42). RESULTS: Median follow-up was 9 months (1-57). Five metastases recurred. One- and 2-year metastasis local control rates were 91.3 and 84% and 1- and 2-year brain control rates were 65 and 57%, respectively. Six patients died of brain metastasis evolution, and three of leptomeningeal carcinomatosis. One- and 2-year overall survival rates were 31 and 28%, respectively. According to univariate analysis, KPS, RPA class, SIR score and interval between WBRT and radiosurgery were prognostic factors of overall survival and brain free-disease survival. According to multivariate analysis, RPA was an independent factor of overall survival and brain free-disease survival, and the interval between WBRT and radiosurgery longer than 14 months was associated with longer brain free-disease survival. Side effects were minimal, with only two cases of headaches and two of grade 2 alopecia. CONCLUSION: Salvage radiosurgery of metastasis recurring after whole brain irradiation is an effective and accurate treatment which could be proposed to patients with a KPS>70 and a primary tumour controlled or indolent. We recommend that a dose not exceeding 14 Gy should be delivered to an isodose representing 70% of the maximal dose since local control observed rate was similar to that previously published in literature with upper dose and side effects were minimal.

Extent of tumor-brain interface: a new tool to predict evolution of malignant gliomas.

OBJECT: Tumor size is one of the features commonly used in oncology to predict disease evolution. However, for most primary brain tumors it is not predictive of outcome. Taking advantage of a gene therapy trial in which recurrences of glioblastoma were targeted with suicide genes, the authors developed a new parameter: the extent of tumor-brain interface--also called surface of tumor volume (STV)--to better describe three-dimensional conformation and the relationship between tumors and the surrounding normal tissue. Correlations between the STV and the usual clinical parameters were analyzed. METHODS: Between 1995 and 1998, 16 patients presenting with recurrent glioblastomas were enrolled in this study. Preoperative magnetic resonance images were analyzed on a separate workstation; the interface between tumor and normal brain tissue was measured on each 3-mm-thick section to assess STV. The mean STV was 29.2 cm2, and the mean tumor volume (TV) was 23.8 cm3. The STV was significantly correlated with survival (Spearman test: r = -0.54, p = 0.03), but TV was not (Spearman test: r = -0.39, p = 0.15). A separate analysis of responding and nonresponding patients showed that, as expected, STV was negatively correlated with survival among nonresponding patients (p = 0.04), but that among responding patients there was a positive tendency between STV and survival. CONCLUSIONS: These findings indicate that STV may be a useful tool for predicting the evolution of malignant glioma. Moreover, in future gene therapy trials in which such in situ approaches are used, increasing density and improved distribution of transfer cells should be taken into consideration as an important issue for efficacy.

Magnetic resonance-guided stereotactic biopsies: results in 100 consecutive cases.

BACKGROUND: We present the results of 100 consecutive magnetic resonance (MR)-guided biopsies in cases where computerised tomography (CT) guiding was considered dangerous or impossible. METHOD: MR guiding was preferred to CT guiding for cases where lesions were located in the central area, or were not clearly visible on CT scan, or where the visualization of vessels was considered necessary. For most of the patients, calculation of target co-ordinates was performed using dedicated software enabling trajectory previsualization. There were 62 cases of contrast enhanced lesions, 32 cases of lesions without contrast enhancement, and 6 cases of very small lesions appearing hyperintense on T2-weighted images. FINDINGS: Biopsies allowed a histological diagnosis in 92 cases. In 8 cases, the biopsy was negative (necrosis, gliosis or normal brain tissue). Three patients had a transient worsening of their neurological disturbances. Two patient had a non-regressive loss of motor function. No patient died. INTERPRETATION: MR guiding for stereotactic biopsies was effective for CT-invisible or ill-defined lesions, lesions located in functional or densely vascularized areas and in the brain stem. The rate of postoperative complications was equivalent to or less than that reported in series of CT-guided biopsies.

Benign recurrence of a cerebellar pilocytic astrocytoma 45 years after gross total resection.

OBJECTIVE AND IMPORTANCE: Cerebellar pilocytic astrocytomas are common benign tumours of childhood and mostly easy to treat because of their location and conformation. Nevertheless, unpredictable recurrence as well as the lack of features to predict the rare malignant changes after first removal, still represent a challenging problem. CLINICAL PRESENTATION: A 54 years old man presented with a recurrence of a cerebellar pilocytic astrocytoma 45 years after complete removal. INTERVENTION: Gross total resection was performed. The pathological examination confirmed the same histological pattern as the first tumour. DISCUSSION: Current opinions about management and recurrence of pilocytic astrocytomas are discussed with a review of the literature.

[Surgery of epilepsy: current status]. / Chirurgie de l'épilepsie. Etat actuel.

PRELIMINARY EXPLORATIONS: The advent of magnetic resonance imaging and its capacity to detect fine structural injury and SPECT and PET functional imaging as well as the generalization of EEG-video and the simplification of intracranial electrode implantation techniques has given a whole new life to surgery in epilepsy. Preoperative explorations are shorter and less invasive, allowing surgery without implantation of intracranial electrodes in more than 70% of the cases. SURGERY: New surgical techniques (subpial transection, neuro-navigation...) and improvement in well-known procedures (amygdalo-hippocampectomy...) has made it possible to propose lower risk procedures with minimal trauma (overall complication rate < 10%), particularly for temporal epilepsy where the success rate is greater than 80%. FUNDAMENTAL RULE: The key to success however directly depends on rigorous application of the fundamental rule of anatomo-electro-clinical correlation.

Correspondence between functional magnetic resonance imaging somatotopy and individual brain anatomy of the central region: comparison with intraoperative stimulation in patients with brain tumors.

OBJECT: The goal of this study was to determine the somatotopical structure-function relationships of the primary motor cortex in individual patients by using functional magnetic resonance (fMR) imaging. This was done to assess whether there is a displacement of functional areas compared with anatomical landmarks in patients harboring brain tumors close to the central region, and to validate these findings with intraoperative cortical stimulation. METHODS: One hundred twenty hemispheres in 60 patients were studied by obtaining blood oxygen level-dependent fMR images in patients while they performed movements of the foot, hand, and face on both sides. There was a good correspondence between anatomical landmarks in the deep portion of the central sulcus on axial slices and the somatotopical organization of primary motor areas. Pixels activated during hand movements were centered on a small characteristic digitation; those activated during movements in the face and foot areas were located in the lower portion of the central sulcus (lateral to the hand area) and around the termination of the central sulcus, respectively. In diseased hemispheres, signal-intensity changes were still observed in the projection of the expected anatomical area. The fMR imaging data mapped intraoperative electrical stimulation in 92% of positive sites. CONCLUSIONS: There was a high correspondence between the somatotopical anatomy and function in the central sulcus, which was similar in normal and diseased hemispheres. The fMR imaging and electrical stimulation data were highly concordant. These findings may enable the neurosurgeon to locate primary motor areas more easily during surgery.

Bilateral subthalamic stimulation for Parkinson's disease by using three-dimensional stereotactic magnetic resonance imaging and electrophysiological guidance.

OBJECT: Several methods are used for stereotactically guided implantation of electrodes into the subthalamic nucleus (STN) for continuous high-frequency stimulation in the treatment of Parkinson's disease (PD). The authors present a stereotactic magnetic resonance (MR) method relying on three-dimensional (3D) T1-weighted images for surgical planning and multiplanar T2-weighted images for direct visualization of the STN, coupled with electrophysiological recording and stimulation guidance. METHODS: Twelve patients with advanced PD were enrolled in this study of bilateral STN implantation. Both STNs were visible as 3D ovoid biconvex hypointense structures located in the upper mesencephalon. The coordinates of the centers of the STNs were determined with reference to the patient's anterior commissure-posterior commissure line by using a new landmark, the anterior border of the red nucleus. Electrophysiological monitoring through five parallel tracks was performed simultaneously to define the functional target accurately. Microelectrode recording identified high-frequency, spontaneous, movement-related activity and tremor-related cells within the STNs. Acute STN macrostimulation improved contralateral rigidity and akinesia, suppressed tremor when present, and could induce dyskinesias. The central track, which was directed at the predetermined target by using MR imaging, was selected for implantation of 19 of 24 electrodes. No surgical complications were noted. CONCLUSIONS: At evaluation 6 months after surgery, continuous STN stimulation was shown to have improved parkinsonian motor disability by 64% and 78% in the "off' and "on" medication states, respectively. Antiparkinsonian drug treatment was reduced by 70% in 10 patients and withdrawn in two patients. The severity of levodopa-induced dyskinesias was reduced by 83% and motor fluctuations by 88%. Continuous high-frequency stimulation of the STN applied through electrodes implanted with the aid of 3D MR imaging and electrophysiological guidance is a safe and effective therapy for patients suffering from severe, advanced levodopa-responsive PD.

Parenchymal pineal tumors: a clinicopathological study of 76 cases.

PURPOSE: The aim of this study was to identify factors that could lead to optimization of the management of pineal parenchymal tumors (PPT) which remains equivocal and controversial. METHODS AND MATERIALS: In order to determine factors that influence PPT prognosis, a series of 76 consecutive patients from 12 European centers with histologically proven tumors was retrospectively reviewed. The clinical records and material for histologic review were available in all cases. Follow-up was achieved in 90% of cases. RESULTS: According to WHO classification, there were 19 pineocytomas, 28 intermediate and mixed PPT, and 29 pineoblastomas. According to a four-grade institutional classification, there were 11 Grade 1, 27 Grade 2, 20 Grade 3, and 18 Grade 4. Surgical resection was attempted in 44 patients, whereas 30 had biopsy only. In one case, diagnosis was made at autopsy and in another on spinal deposits. Forty-four patients were irradiated following surgery, 15 patients received chemotherapy. Forty-one patients were alive (median follow-up: 85 months); 9 patients died perioperatively; 26 patients relapsed. Univariate analysis showed a good outcome correlated with age above 20 years, tumor diameter less than 25 mm, and low-grade histology. Multivariate analysis confirmed histology and tumor volume to be significant independent prognostic factors. The extent of surgery and radiotherapy had no clear influence on survival. CONCLUSIONS: This review highlights the prognostic features of PPT and may help to determine treatment strategies based on radiologic and pathologic characteristics.

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.

[First treatment for brain metastases by stereotactic radiosurgery]. / Traitement premier des métastases cérébrales par irradiation en conditions stéréotaxiques.

Local control of brain metastases is better with first treatment by stereotactic radiosurgery than with radiosurgery for recurrence. We reported a retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery realised in first intention. From January 1994 to December 1997, 26 patients presenting with 43 metastases underwent radiosurgery. The median age was 61 years and the median Karnofsky index 70. Primary sites included: lung (12 patients), kidney (7 patients), breast (2 patients), colon (1 patient), melanoma (2 patients), osteosarcoma (1 patient), it was unknown for one patient. Seven patients had extracranial metastases. Twenty-one sessions of radiosurgery have been realized for one metastase, and 9 for two, three or four lesions. The median diameter was 21 mm and the median volume 1.8 cm3. The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. Forty-two metastases were evaluable for response analysis. The overall local control rate was 90.5% and the 1-year, 2- and 3-year actuarial rates were 85% and 75%. In univariate analysis, theorical radioresistance was significantly associated with better local control (100% versus 77%, p < 0.05). All patients were evaluable for survival. The median survival rate was 15 months. Four patients had a symptomatic oedema (RTOG grade II). Two lesions have required a surgical excision. In conclusion, low dose radiosurgery (14 Gy delivered at the periphery of metastasis) can be proposed in first intention for brain metastases, in particularly for theorical radioresistant lesions.

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.

[The value of MRI for the diagnosis of meningeal hemorrhage during vasospasm]. / Intérêt de l'IRM pour le diagnostic d'hémorragie méningée en période de spasme.

Retrospectively, subarachnoidal hemorrhage can be misdiagnosed when the acute event did not bring the patient to medical attention, when clinical history is unclear and the CT scan is normal. Moreover, days after subarachnoid hemorrhage, cerebral vasospasm can result in neurological deficits that are indistinguishable from that produced by other causes of stroke. We report our experience with two patients who presented with symptoms of ischemia due to an arterial vasospasm that followed unrecognized rupture of an intracranial aneurysm. In both cases, CT scan failed to detect subarachnoid hemorrhage while MR detected the presence of signal changes in the subarachnoidal spaces associated with an ischemic stroke in one case. Neurological symptoms resolved completely after aneurysm treatment. MR can be a critical for the diagnosis of stroke secondary to vasospasm in order to prescribe an adapted treatment, avoid anticoagulant or thrombolytic therapy, and rapidly exclude the recently ruptured aneurysm to protect the patient from the risk of rebleeding.

A phase I/II study of herpes simplex virus type 1 thymidine kinase "suicide" gene therapy for recurrent glioblastoma. Study Group on Gene Therapy for Glioblastoma.

Despite extensive surgery for glioblastoma, residual tumor cells always lead to relapse. Gene therapy based on retrovirus-mediated gene transfer of herpes simplex virus type 1 thymidine kinase (HSV-1 TK), which specifically sensitizes dividing cells to ganciclovir (GCV) toxicity, may help eradicate such cells. During glioblastoma surgery, HSV-1 TK retroviral vector-producing cells (M11) were injected into the surgical cavity margins after tumor debulking. After a 7-day transduction period, GCV was administered for 14 days. Safety was assessed by clinical and laboratory evaluations, and efficacy was assessed by MRI-based relapse-free survival at month 4 and by overall survival. Twelve patients with recurrent glioblastoma were treated without serious adverse events related to M11 cell administration or GCV. Quality of life was not negatively influenced by this treatment. Overall median survival was 206 days, with 25% of the patients surviving longer than 12 months. At 4 months after treatment, 4 of 12 patients had no recurrence; their median overall survival was 528 days, compared with 194 days for patients with recurrence (p=0.03 by the log rank test). One patient is still free of detectable recurrence, steroid free and independent, 2.8 years after treatment. Thus, brain injections of M11 retroviral vector-producing cells for glioblastoma HSV-1 TK gene therapy were well tolerated and associated with significant therapeutic responses. These results warrant further development of this therapeutic strategy in brain tumor, including recurrent glioblastoma.

Glossopharyngeal neuralgia associated with a vascular loop demonstrated by magnetic resonance imaging.

We report two cases of glossopharyngeal neuralgia associated with a vascular loop of the postero-inferior cerebellar artery, diagnosed by magnetic resonance imaging. Reviewing the literature, we found this to be the first report of a magnetic resonance-validated vascular abnormality related to such a condition. One patient was cured by surgical decompression, confirming the role of the abnormal vessel in the pain. As with trigeminal neuralgia, a possible vascular aetiology should be considered in glossopharyngeal neuralgia.