Mutations within the MGC4607 gene cause cerebral cavernous malformations.

Cerebral cavernous malformations (CCM) are hamartomatous vascular malformations characterized by abnormally enlarged capillary cavities without intervening brain parenchyma. They cause seizures and focal neurological deficits due to cerebral hemorrhages. CCM loci have already been assigned to chromosomes 7q (CCM1), 7p (CCM2), and 3q (CCM3) and have been identified in 40%, 20%, and 40%, respectively, of families with CCM. Loss-of-function mutations have been identified in CCM1/KRIT1, the sole CCM gene identified to date. We report here the identification of MGC4607 as the CCM2 gene. We first reduced the size of the CCM2 interval from 22 cM to 7.5 cM by genetic linkage analysis. We then hypothesized that large deletions might be involved in the disorder, as already reported in other hamartomatous conditions, such as tuberous sclerosis or neurofibromatosis. We performed a high-density microsatellite genotyping of this 7.5-cM interval to search for putative null alleles in 30 unrelated families, and we identified, in 2 unrelated families, null alleles that were the result of deletions within a 350-kb interval flanked by markers D7S478 and D7S621. Additional microsatellite and single-nucleotide polymorphism genotyping showed that these two distinct deletions overlapped and that both of the two deleted the first exon of MGC4607, a known gene of unknown function. In both families, one of the two MGC4607 transcripts was not detected. We then identified eight additional point mutations within MGC4607 in eight of the remaining families. One of them led to the alteration of the initiation codon and five of them to a premature termination codon, including one nonsense, one frameshift, and three splice-site mutations. All these mutations cosegregated with the disease in the families and were not observed in 192 control chromosomes. MGC4607 is so far unrelated to any known gene family. Its implication in CCMs strongly suggests that it is a new player in vascular morphogenesis.

[Percutaneous sacral thermorhizotomy to treat equinism of spastic cerebral palsy children]. / Thermorhizotomie sacrée percutanée pour équinisme spastique de l'enfant infirme moteur cérébral.

We propose to evaluate the effect of sacral percutaneous thermorhizotomy on cerebral palsy children. A prospective study including 29 children followed by a multidisciplinary team was conducted from 1990 to 2000. A thermal radiofrequency lesion of the first sacral root was obtained by percutaneous puncture of the posterior intervertebral foramen with evaluation by stimulation of the best motor response for the minimal threshold (<0.5 volts). The efficacy of the lesion was evaluated by testing and modification of the stimulation threshold obtained (x 2). The results on spasticity was evaluated using the Held score and the functional effect on walking, and classified as "good" (9 cases), "efficacy" (6 cases) and "nil" (4 cases). Indications of the procedure are discussed during the walking acquisition period and growing period of the cerebral palsy child.

[Neurosurgical treatment of hyperactive bladder in spinal cord injury patients]. / Traitement neurochirurgical de la vessie hyperactive chez le blessé médullaire.

OBJECTIVES: We report long-term results of posterior sacral root rhizotomies in combination with Finetech-Brindley anterior sacral root stimulators implanted intradurally in 20 spinal cord injury patients. MATERIAL: and methods: The 14 female and 6 male patients included 14 paraplegics and 6 tetraplegics. All of them initially presented hyperactive bladder, detrusor-sphincter dyssynergia, recurrent urinary tract infection and performed (self) intermittent catheterization. Prior to implantation, an intrathecal test using bupivacaine was performed to confirm the compliances of the bladder. The main indication for implantation was persistent urinary incontinence refractory to medical therapy. RESULTS: After implantation the mean follow-up was 4,5 years. In all, 18 patients used the stimulator alone for bladder emptying and 18 patients were completely continent. The mean bladder capacity increased from 190 ml preoperatively to 460 ml after the operation. The mean residual urinary volume was reduced from 90 ml to 25 ml. No changes were noted by renal isotopic scanning in upper urinary tracts of patients. In 1 patient, a second extradural implant was performed. DISCUSSION: This article also include an overview of a) the different available sites where application of electrical stimulation results in a detrusor contraction, b) the benefits and disadvantages of the sacral posterior rhizotomy, c) selective stimulation techniques that allow selective detrusor activation by sacral root stimulation. CONCLUSION: Sacral anterior root stimulation combined with sacral posterior rhizotomy is a valuable method to restore bladder functions in spinal cord injured patients suffering from hyperactive bladder refractory to medical therapy.

Magnetic resonance imaging stereotactic target localization for deep brain stimulation in dystonic children.

OBJECT: The actual distortion present in a given series of magnetic resonance (MR) images is difficult to establish. The purpose of this study was to validate an MR imaging-based methodology for stereotactic targeting of the internal globus pallidus during electrode implantation in children in whom general anesthesia had been induced. METHODS: Twelve children (mean follow up 1 year) suffering from generalized dystonia were treated with deep brain stimulation by using a head frame and MR imaging. To analyze the influence of distortions at every step of the procedure, the geometrical characteristics of the frame were first controlled using the localizer as a phantom. Then pre- and postoperative coordinates of fixed anatomical landmarks and electrode positions, both determined with the head frame in place, were statistically compared. No significant difference was observed between theoretical and measured dimensions of the localizer (Student's t-test, ¿t¿ > 2.2 for 12 patients) in the x, y, and z directions. No significant differences were observed (Wilcoxon paired-sample test) between the following: 1) pre- and postoperative coordinates of the anterior commissure (AC) (deltax = 0.3+/-0.29 mm and deltay = 0.34+/-0.32 mm) and posterior commissure (PC) (deltax = 0.15+/-0.18 mm and deltay = 0.34+/-0.25 mm); 2) pre- and postoperative AC-PC distance (deltaL = 0.33+/-0.22 mm); and 3) preoperative target and final electrode position coordinates (deltax = 0.24+/-0.22 mm; deltay = 0.19+/-0.16 mm). CONCLUSIONS: In the authors' center, MR imaging distortions did not induce detectable errors during stereotactic surgery in dystonic children. Target localization and electrode implantation could be achieved using MR imaging alone after induction of general anesthesia. The remarkable postoperative improvement in these patients confirmed the accuracy of the procedure (Burke-Marsden-Fahn Dystonia Rating Scale score delta = -83.8%).

[Intra-orbital decompression of the optic nerve by opening the peri-optic meninges in the treatment of severe optic neuropathies complicating benign intracranial hypertension]. / Décompression intra-orbitaire du nerf optique par ouverture des méninges péri-optiques dans le traitement des neuropathies optiques sévères compliquant une hypertension intracrânienne bénigne.

Papilledema from benign intracranial hypertension can cause severe loss of visual acuity and visual field, with an optic neuropathy. We report a study of 5 patients with benign intracranial hypertension, and severe visual loss (visual field loss and visual acuity reduced to 1/10 or less) not improved by medical therapy (acetazolamide). We performed unilateral orbital decompression of the optic nerve sheath. No major operative complication was noted. Follow-up ranged from 11 months to 23 months, with an average of sixteen months. Visual function improvement was noted within 3 months after operation in 4 patients (for 2 eyes on the surgical side improvement of 2/10 and 5/10, for 3 eyes on the opposite surgical side average improvement of 4.6/10). The other patient showed improvement, but no significant. Optic nerve sheath decompression in benign intracranial hypertension seems to be a safe procedure and a therapeutic option in the management of raised intracranial pressure complicated by optic neuropathy with severe visual loss.

[Treatment of early-onset generalized dystonia by chronic bilateral stimulation of the internal globus pallidus. Apropos of a case]. / Traitement de la dystonie généralisée à début précoce par stimulation chronique bilatérale des globus pallidus internes. A propos d'un cas.

Dystonia musculorum deformans is an inherited severe disease, with a wide clinical polymorphism. The most severe clinical forms with early onset carry a high risk of life-threatening complications. In the absence of any efficient medical treatment, bilateral pallidotomy has previously been reported to be of value in the management of this disease. We report the first clinical case of a severe early-onset generalized dystonia dramatically improved by a bilateral stimulation of the internal globus pallidus. In November 1996, we proposed this neurosurgical procedure for a 8-year-old girl, who had suffered since the age of 3 from severe generalized dystonia, and who progressively became totally dependent and bedridden. She had been under sedation and permanent controlled respiratory assistance for the last two months. The etiology of the disease remained unknown (the DYT1 mutation was absent). Under general anesthesia, we bilaterally implanted a four-contacts electrode in the internal globus pallidus, using the Leksell's stereotactic frame and a 1.5 tesla MRI control. A dramatic improvement was noted 6 weeks later and led us to connect the two electrodes to neurostimulators inserted under the abdominal skin.

Anatomic basis for the treatment of aneurysms of the upper cervical segment of the internal carotid artery by extra-intracranial cervico-petrous bypass with inverted "in situ" saphenous vein graft.

In the surgical treatment of aneurysms of the upper cervical portion of the internal carotid a., exclusion of the affected vascular segment combined with an extra-anatomic cervico-petrous bypass using a vein graft (great saphenous v.) may be considered. One of the problems specific to these extra-anatomic bypasses is associated with the sub-cutaneous positioning of the vein graft, exposing it to risks of angulation, torsion or extrinsic compression that may lead to early venous thrombosis. We suggest an alternative technique using the principle of telescoping and consisting of positioning the vein graft within the cervical portion of the artery ("in situ" bypass). The cervical portion of the ICA may be used as a tunnel for the vein graft since there are no collateral arterial branches at this level. The technical features of such a bypass are defined by means of an anatomo-surgical study in the cadaver: exposure of the petrous portion of the internal carotid a. in its horizontal segment by subtemporal access, exposure of the ICA in the neck, transverse arteriotomies of the ICA, angioplasty with a Fogarty balloon, intracarotid telescoping of a saphenous vein graft from the cervical to the petrous region, distal end-to-end anastomosis between the vein graft and the petrous portion of the ICA, and proximal end-to-end anastomosis between the vein graft and the cervical portion of the ICA.

[Cyst of the conus masquerading as motor neuron disease]. / Kyste du cône médullaire simulant une maladie du motoneurone.

We report on a patient presenting with rapidly progressive painless paraplegia, amyotrophy and fasciculations masquerading as motoneuron disease. There were no bowel or bladder involvement but the patient noted mild paresthesia on the external part of the right foot and hypertrophy of the right calve was present. While lumbar CT Scan was normal, MRI showed a large cyst of the conus. Analysis of the cyst concluded to a benign cyst of the conus. Paraplegia resolved after surgery and after one year, no relapse was observed so that an hidden ependymoma appeared unlikely.

[Ectopic intraspinal extradural anaplastic ependymoma in an infant]. / Ependymome anaplasique ectopique intrarachidien extradural chez un nourrisson.

BACKGROUND: Ependymomas represent about 10% of the spinal tumors in children. Some of them may be unusually located. CASE REPORT: A 10-month-old boy was admitted for an abdominal mass syndrome with dehydration asthenia and acute bladder dysfunction. A few hours later, he developed a flaccid paraplegia. Ultrasonic and magnetic resonance spinal imaging showed a giant intraspinal tumor extending from T9 to IA level, posteriorly located to the dural compartment, widening the spinal cord. Ultrasonography also showed right ureterohydronephrosis due to the neurological bladder dysfunction. A conservative laminotomy-laminoplasty was performed in emergency. Total removal of the tumor that was attached to the right dorsal root was achieved extradurally, requiring resection of the proximal part of the root. Histological features were typical of malignant ependymoma. Chemotherapy was initiated 2 weeks later. The severe renal destruction and the persistent bladder dysfunction led to a heminephrectomy and a cystostomy, 3 weeks later. The neurological recovery was only partial with a follow-up of 18 months. CONCLUSION: Ectopic intraspinal extradural localization of ependymomas is rare and their development from a nerve root is exceptional.

[Symptomatic aneurysms of the postero-inferior cerebellar artery. A multicenter retrospective study of 29 cases]. / Anévrysmes symptomatiques de l'artère cérébelleuse postéro-inférieure. Etude rétrospective multicentrique de 29 cas.

A multicenter retrospective study of 29 cases of posterior inferior cerebellar artery is reported. Over a period of 21 years, the frequency of posterior inferior cerebellar artery aneurysm among all intracranial aneurysm was estimated to 1.38 p. 100 of cases of aneurysms followed by 3 University Hospitals. Frequency of rupture appeared to be very high (93 p. 100) in this series probably because of the type of selection. Average grade of presentation according to Hunt and Hess classification being < III in 3 fourth of the cases. Neither clinical presentation nor suspicious etiological factors were specific of this localization. Only two cases were of pseudotumoral appearance. Positive diagnosis of subarachnoid hemorrhage was made by CT scan. Angiograms gave diagnosis of localization of the malformation and its type. Intraventricular hemorrhage was found in 62 p. 100 of our cases: all had hemorrhage of the fourth ventricle. Hydrocephaly was more frequent as compared to supratentorial localizations, Vasospasm was less frequent as in supratentorial localizations. Nimodipin seems to be efficient. Therapeutic possibilities are primary dominated by surgery with good results when it is possible. Endovascular treatment is under evaluation.

Total endovascular occlusion of a giant direct arteriovenous fistula in the posterior fossa in a case of Rendu-Osler-Weber disease.

We report a case of giant single-hole direct arteriovenous fistula (AVF) located in the posterior fossa of a child with Rendu-Osler-Weber disease (ROW). There is neither a clinical nor an angioarchitectural difference between AVFs associated with ROW and sporadic AVFs, but ROW should be suspected in children with multifocal pial AVFs. Transarterial embolization was performed to obliterate the AVF in a unique procedure using simultaneous bifemoral catheterization. At follow up 4 years later, the clinical examination was normal. Control MR scans and angiography showed the total occlusion of the fistula, permanent thrombosis of the venous pouch, and disappearance of the abnormal venous drainage. In this case, the endovascular procedure was available and we estimated that it represented a lesser risk than the surgical approach (risk of hemorrhage and risk of thrombosis involving the feeding arteries and the brain stem venous drainage). Furthermore, it avoids craniotomy and reduces the duration of hospitalization.

[Arachnoid cysts and subdural hematomas]. / Kystes arachnoïdiens et hématomes sous-duraux.

Arachnoid cysts of the middle cerebral fossa is a not uncommon lesion which can occur in young subjects, sometimes after minimal head trauma. Subdural hematomas and sometimes intracystic hemorrhage may develop. We report a personal series of seven cases seen in young subjects (6-24 years). Clinical presentation was not specific, the complication usually being revealed by signs of intracranial hypertension. The pathogenesis of subdural hematoma is discussed. Magnetic resonance imaging is the most useful diagnostic tool, providing excellent tissue specificity, although CT scan is often used to visualize a subdural hematoma and subsequent arachnoid cyst. Treatment relies on surgery to empty the subdural hematoma and remove compression. There has been no real consensus on treatment modalities. Long-term prognosis is good in most cases.

Cervical-to-petrous internal carotid artery saphenous vein in situ bypass for the treatment of a high cervical dissecting aneurysm: technical case report.

OBJECTIVE AND IMPORTANCE: We describe a novel cervical-to-petrous internal carotid artery (ICA) saphenous vein in situ bypass for the treatment of a high cervical dissecting aneurysm. The cervical ICA has no major collateral branches and can be used as a tunnel for the vein graft. CLINICAL PRESENTATIONS: A 25-year-old man was involved in a car accident. A cerebral angiogram revealed a right ICA dissection with aneurysm formation at the C1-C2 level. The patient recovered fully and was anticoagulated. Six months after the initial angiogram, a second angiogram disclosed ICA stenosis (80%) and persistence of the traumatic dissecting aneurysm. Definitive surgical bypass was considered the most appropriate course of action. TECHNIQUE: The horizontal portion of the petrous ICA was exposed by an extradural subtemporal approach. The cervical arteries were exposed by a separate surgical incision. After dividing the petrous ICA and the cervical ICA, the cervical ICA was dilated using a Fogarty balloon embolectomy catheter. A saphenous vein graft was inserted inside the lumen of the cervical ICA and was anastomosed to the ICA end-to-end both proximally and distally (cervical-to-petrous ICA in situ bypass). The graft was patent on the follow-up angiogram. CONCLUSION: We describe a new technique that could be considered an alternative to the classical extra-anatomic cervical-to-petrous ICA bypass procedures.

[Sub-temporal supra-petrous approach to the horizontal portion of the sub-petrous internal carotid artery. Technique, indications, incidents and accidents]. / Exposition par voie sous-temporale sus-pétreuse de l'artère carotide interne intra-pétreuse dans sa portion horizontale. Technique, indications, incidents et accidents.

Cavernous sinus exploration, anterior middle fossa transpetrous approach, and saphenous vein graft bypass require proximal control of the horizontal segment of the petrous internal carotid artery. Exposing the petrous portion of the internal carotid artery is not without the potential for serious complications (cochlea, facial nerve, auditory tube, musculus tensor tympani). With guidance from the classicaly landmarks within Glasscock's triangle, the bony petrous carotid canal can be unroofed. The authors describe an alternative method for obtaining direct vascular control under the trigeminal ganglion, safety unroofing of the carotid canal and control of the posterior face of the carotid bend. The indications, advantages, and disadvantages of this approach are described in details, along with its use in seven patients.

Monitoring sodium methohexital distribution with [99mTc]HMPAO with single photon emission computed tomography during Wada test.

Twenty-five consecutive patients being considered for surgery for intractable epilepsy had intracarotid sodium methohexital procedures (ISM) as part of their evaluation. The lipophilic brain SPECT agent, [99mTc]hexamethylpropylene aminoxime (HMPAO), was administered intravenously during the procedure to determine the intracerebral distribution of methohexital. The validity of the ISM depends on consistent delivery of the anesthetizing agent to one hemisphere, including the mesial structures of the temporal lobe. To prevent postoperative language and memory deficits, correct interpretation of the test results supposes a reliable knowledge of which regions of the brain have been anesthetized. Currently, no absolute criteria allow determination of the level and topographical extent of the anesthesia. We compared results of HMPAO-SPECT with clinical and EEG video-monitoring data and with results of digital subtraction angiography (DSA) performed during the test. In all patients, the effect of SM was ipsilateral cerebral hypoperfusion on SPECT and crossed cerebellar diaschisis. The distribution of HMPAO varied from patient to patient. The delivery of SM to mesial temporal lobe structures was not constant. Using nonparametric tests, we demonstrated a statistically significant relationship between hypoperfusion on SPECT and duration of hemiplegia but not with the duration of aphasia. Hypoperfusion on SPECT was also related to the onset and duration of drug-induced delta activity on EEG. SPECT showed a statistically different distribution of SM in the brain from that predicted with DSA. We present our experience with HMPAO-SPECT use for mapping the distribution of methohexital's effects during the ISM (Wada test). We confirm the results of previous studies that SPECT assessment may be an excellent way of determining the distribution of barbiturate during the examination. It increases confidence in interpreting results of speech and memory testing by detecting either contralateral diffusion of the drug due to crossflow between hemispheres or insufficient quantitative delivery to the homolateral hemisphere.

Early restructuration of consciousness after traumatic coma.

Recovery of consciousness after acute brain injury is a remarkable phenomenon, yet, not completely understood. We describe the early clinical stages of recovery of consciousness in 48 selected patients by means of different items of the Glasgow Coma and Liege Coma Scales. Arousal, expressed by the stimulated opening of the eyes (E2) was correlated with the appearance of the localizing pain response (M5), with the capacity to obey commands (M6), with the opening of the eyes (E4) and with the blink reflex (R5). This study confirms the classical clinical sequence of arousal and recovery of consciousness characterized by the consecutive appearance of E2, R5, E4, M5 and M6. When the appearance of E2 and R5 are considered separately, we noticed a significant difference, suggesting different structural and functional brain recovery processes.

Clinical recovery of consciousness after traumatic coma.

OBJECTIVE: To describe early clinical stages in the recovery of consciousness, using selected items from the Glasgow Coma Scale and the Liège Coma Scale. DESIGN: Validation cohort study, conducted in a tertiary care center. SETTING: Neurosurgical intensive therapy unit in a university teaching hospital. PATIENTS: Patients (n = 137) with traumatic coma who were selected according to the following criteria: a) coma due to blunt head trauma with an initial Glasgow Coma Score of < or = 7; b) admission to the neurosurgical intensive therapy unit within the first 24 hrs after trauma; c) patients > 14 yrs of age; requiring endotracheal intubation, mechanical ventilation, and the administration of drugs; and d) survival period allowing analysis of the recovery of consciousness. MEASUREMENTS AND MAIN RESULTS: Arousal, as expressed by stimulated opening of the eyes and recorded as a delay in days, was correlated with the appearance of the localized pain response, capacity to obey commands, blink reflex, and the cessation of drugs in three groups of patients. These groups were defined according to the time in which there was an appearance of the stimulated opening of the eyes: < 8 days (group 1); between 8 and 15 days (group 2); and after 15 days (group 3). When the three groups of patients were compared, significant differences existed between the mean delays of appearance of stimulated eye opening and the appearance of the blink reflex. Extubation coincided with the appearance of spontaneous eye opening, with a mean delay of 13.5 days. CONCLUSIONS: This study confirms the classical clinical sequence of arousal and recovery of consciousness, with the appearance of stimulated eye opening and the blink reflex first, followed by spontaneous eye opening, and the capacity to obey commands in intubated, traumatized, coma patients. A direct correlation existed between the delay of arousal and the complete recovery of consciousness. When groups of patients with various mean delays for the appearance of stimulated eye opening are considered, reappearance of the blink reflex did not always coincide with stimulated eye opening, suggesting differing structural and functional brain recovery processes.

Disco-computed tomography in extraforaminal and foraminal lumbar disc herniation: influence on surgical approaches.

Between January 1990 and February 1992, a total of 301 patients underwent discectomy for lumbar disc herniation; 29 had an extreme lateral herniation, i.e., foraminal or extraforaminal. The intervertebral foramen is a three-dimensional area demarcated primarily by the pedicles; we call it the lateral interpedicular compartment. The extraforaminal zone is the space outside the lateral border of the pedicles. All patients were evaluated by computed tomography (CT), water soluble myelography, postmyelographic CT scanning, or magnetic resonance imaging. Fifteen patients consecutively underwent disco-enhanced CT to adjust a correct diagnosis and to distinguish extraforaminal from foraminal herniation. In 10 cases of extraforaminal herniation, a selective radicular decompression with good-to-excellent clinical results was achieved by an extra-axial lateral decompression of the interpedicular compartment, with preservation of the facet joint. The operative target was the lateral aspect of the pars interarticularis and not the intertransverse space, as previously described. In two cases of both foraminal and extraforaminal herniation, the same technique was used. Fourteen patients with foraminal disc herniation and three patients with both foraminal and extraforaminal herniation underwent a standard intervertebral foraminotomy. An accurate preoperative diagnosis established by disco-CT is crucial in order to select the most suitable surgical approach.