Ex vivo study of dentate gyrus neurogenesis in human pharmacoresistant temporal lobe epilepsy.

AIMS: Neurogenesis in adult humans occurs in at least two areas of the brain, the subventricular zone of the telencephalon and the subgranular layer of the dentate gyrus in the hippocampal formation. We studied dentate gyrus subgranular layer neurogenesis in patients subjected to tailored antero-mesial temporal resection including amygdalohippocampectomy due to pharmacoresistant temporal lobe epilepsy (TLE) using the in vitro neurosphere assay. METHODS: Sixteen patients were enrolled in the study; mesial temporal sclerosis (MTS) was present in eight patients. Neurogenesis was investigated by ex vivo neurosphere expansion in the presence of mitogens (epidermal growth factor + basic fibroblast growth factor) and spontaneous differentiation after mitogen withdrawal. Growth factor synthesis was investigated by qRT-PCR in neurospheres. RESULTS: We demonstrate that in vitro proliferation of cells derived from dentate gyrus of TLE patients is dependent on disease duration. Moreover, the presence of MTS impairs proliferation. As long as in vitro proliferation occurs, neurogenesis is maintained, and cells expressing a mature neurone phenotype (TuJ1, MAP2, GAD) are spontaneously formed after mitogen withdrawal. Finally, formed neurospheres express mRNAs encoding for growth (vascular endothelial growth factor) as well as neurotrophic factors (brain-derived neurotrophic factor, ciliary neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor). CONCLUSION: We demonstrated that residual neurogenesis in the subgranular layer of the dentate gyrus in TLE is dependent on diseases duration and absent in MTS.

Thalamic cavernous malformations.

BACKGROUND: Only few anecdotal reports and small series of thalamic cavernous malformations have been reported. It follows that the clinical behavior and management are poorly understood; in particular, experiences with the surgical treatment of these lesions are scarce. METHODS: The clinical course, treatment, and outcome of 12 patients (10 females and 2 males, mean age 36 years) with symptomatic cavernous malformations of the thalamus are reviewed. Eight patients (66%) presented with cerebral hemorrhage, one with progressive neurological deficit and three with hydrocephalus/increased intracranial pressure; associated venous anomalies were found in three cases. Treatment consisted of radical surgery in four cases with progressive neurological decline or recurrent disabling hemorrhage, radiosurgery (one case), evacuation of a chronic satellite hematoma (one case), ventriculoperitoneal shunt for hydrocephalus (one case) and observation (five cases). Operative treatment in four cases included transcallosal, trigonal, and occipital interhemispheric approaches. RESULTS: In the surgical group, one patient died, two improved after operation, and one remained the same. Of the patients not operated on radically, one had recurrent hemorrhage 4 months after radiosurgery, one remains stable 8 years after ventriculoperitoneal shunt, and one 3 years after aspiration of a satellite hematoma. Five other patients presenting with thalamic hemorrhage were treated conservatively; recurrent hemorrhage occurred in two cases at 1 month and at 2 years, leaving a mild residual deficit in both cases. Overall, rehemorrhage occurred in four cases (50%) at a mean interval of 18 months after the first bleeding; the annual hemorrhage rate was 6.1%. CONCLUSIONS: Thalamic malformations are more likely to be symptomatic from small hemorrhages compared with lesions in the cerebral hemispheres; progressive growth may also occur with third ventricle invasion or caudal extension to the midbrain. Their high-risk location deters heavy-handed management, but they should not be left long untreated. Both surgery and radiosurgery have been used in the management of thalamic cavernomas reported in the literature. Definite surgical indications include progressive neurological decline and recurrent hemorrhages of malformations abutting the ventricular surface or the posterior incisural space; the complex anatomy of the deep venous system and the association with unexpected venous anomalies complicates the removal of these lesions.

Occult cerebrovascular malformations after irradiation.

OBJECTIVE: It has recently been found that patients receiving cerebral irradiation can develop hemorrhagic dysangiogeneses simulating occult vascular malformations. To analyze this connection, we report on five patients with occult cerebrovascular malformations occurring after "standard" or focused irradiation performed for brain tumors in four patients and for a deep-seated cavernous angioma in one patient. METHODS: All lesions were within the radiation ports. The time interval between irradiation and the detection of the occult vascular malformations varied from 3 to 9 years; the ratio of female to male patients was 4:1. Four patients were < 15 years old when first irradiated. Four patients presented with acute symptoms (headache, vomiting, focal signs) and one was asymptomatic when the lesions were first detected. Serial magnetic resonance imaging scans were available in four patients and a computed tomographic scan in the other patient. RESULTS: The initial appearance was that of a hypointense T1-T2 focus; magnetic resonance imaging then revealed focal or multifocal T1 hyperintensity and T2 mixed signal intensity followed by a late ring of decreased signal intensity. Four patients were operated on and one was under neuroradiological monitoring. Histological features of these lesions included clusters of closely packed vascular spaces resembling cavernous malformations sometimes associated with a thrombosed thick-walled vein with intense hemosiderin deposition and fibroblastic proliferation; telangiectasic changes were also seen in the adjacent brain. CONCLUSION: Increased awareness of occult cerebrovascular malformations is necessary, because their occurrence is not infrequent and they have hemorrhagic potential. Children receiving cerebral irradiation are at greater risk of this complication.

Growth, subsequent bleeding, and de novo appearance of cerebral cavernous angiomas.

In a series of 145 patients with brain cavernous angiomas treated at our hospital in the last 16 years, the angiomas of 18 patients exhibited aggressive biological behavior characterized by recurrent overt bleeding, growth, or de novo appearance. The cavernomas were in the cerebellum in three patients, in the brain stem in one, in the thalamus in four, in the caudate nucleus in two, in the diencephalon in one, and in the white matter of the cerebral hemispheres in seven. Three of these patients suffered from the familial or multiple form of the disease, two were pregnant, three had previously been irradiated for other tumors, and one had been treated by radiosurgery in the past. Overall, new cavernous malformations not previously shown were discovered in six patients. In 10 patients (3 male and 7 female) presenting with recurrent hemorrhages, the mean period of time between bleedings was 11 months (range, 1 wk-3 yr). Eleven patients were treated by definitive surgery, and seven were conservatively treated. One patient with a diencephalic cavernoma died from progressive hypothalamic dysfunction; three patients in the nonsurgical group had repeated symptoms and were left with additional neurological deficits. The outcome of the surgical group was the same (seven patients) or improved (four patients). Risk factors favoring an aggressive behavior included pregnancy, familial or multiple form of the disease, previous whole brain or stereotactic radiotherapy, incomplete removal, brain location, and associated venous malformation. The female preponderance (female to male ratio, 13:5) may also suggest some role of hormonal factors in influencing the biological behavior of cavernous malformations.

Orbital cavernous angiomas: surgical experience on a series of 13 cases.

Cavernous angiomas of the orbit are benign vascular growths, commonly occurring in adults and usually causing a slowly progressive proptosis from their mass effect. These lesions have behavioural and radiological findings different from those of brain cavernous angiomas, probably due to their particular origin and structure. The authors present a surgical series of 13 patients with orbital cavernous angiomas. Complete excision of lesions, with histological diagnosis, was obtained in all the 13 cases. Results were good in 10 patients, while 2 remained clinically unchanged and another one showed acute visual deterioration after a period of postoperative clinical stabilization. The main clinical and radiological characteristics of orbital cavernous angiomas are analyzed, together with their surgical management.

Dissecting aneurysms of the basilar artery.

Ten patients (six men and four women; mean age, 40 yr) with spontaneous dissection of the basilar artery are reported. Clinically, six were admitted with subarachnoid hemorrhage (SAH) and four were admitted with brain stem ischemia. Angiography demonstrated string sign in four patients, pearl reaction in four, double lumen in one, and arterial ectasia with mural retention of contrast medium in one. Magnetic resonance imaging was performed in two patients. Follow-up angiograms or magnetic resonance angiography in six patients showed spontaneous healing in two patients, improvement in two, progression in one, and no change in one. Nine patients were treated medically, and one underwent selective intravascular occlusion of the dissecting aneurysm. One patient died after further SAH, two remain severely disabled, three have residual neurological deficit, and four are in good clinical condition. The most interesting observations in this series include a relatively good course in a substantial number of patients and low further bleeding potential after SAH, the late "globular" evolution, which may be favorable for reconstructive treatment, and the diagnostic value of associated computed tomographic/angiographic findings. Surgical options in basilar dissection are very poor; in some reported cases, wrapping has been tried with disappointing results. In light of the possibility of spontaneous healing or improvement, wrapping should be reserved for only those patients with recurrent SAH or angiographic progression of the dissection.

Dissecting aneurysms of the vertebrobasilar system: study of 16 cases.

In the last 14 years we have encountered 16 patients with spontaneous intracranial dissections of the vertebrobasilar (VB) system (mean age was 46 years and male/female ratio was 10/6). VB dissections presented in eight cases with subarachnoid bleeding and in eight with brainstem, cerebellar, or cerebral ischemia. Three patients had multiple dissections. Ten dissections occurred in the vertebral artery (two extended to the basilar artery), three in the posterior cerebral artery (one bilateral), two in the basilar artery, and one in the posterior inferior cerebellar artery. The angiographic configuration included "string" sign, "pearl and string" sign, fusiform dilation, and double lumen. The following angiographic evolution (available in 11 cases) was that of complete healing (three cases), partial resolution (five cases), progression (one case), and unimproving (two cases). Three patients died (two due to recurrent subarachnoid hemorrhage): two patients were explored surgically (one had further intravascular therapeutic embolization), and the rest were treated conservatively. Not all dissecting aneurysms fared in the same manner, depending either on the location in the VB circulation or on the variable vascular configuration: treatment should be fitted to the timing of diagnosis.

Regressing intracranial carotid occlusions in childhood.

Though detected with increasing frequency, intracranial carotid artery dissection remains less common in infancy. We report on 3 otherwise healthy children aged 8, 12 and 15 years who presented with focal headache and stroke secondary to intracranial carotid occlusive disease consistent with arterial dissection. In 2 cases this was precipitated by strenuous physical exertion. The protean angiographic configuration included long tapered narrowing with focal stenosis, beaded narrowing with Moya Moya vascular network and 'string sign'; occlusion of the anterior cerebral artery was always present. Control angiograms revealed complete or partial recanalization in all cases suggesting self-healing dissection. The clinical course was smooth in all patients, and at long-term follow-up (5, 3, and 2 years) they remain in good neurological condition. Although intracranial carotid dissection has a poor reputation, regression to normal and fair outcome may sometimes occur as in the extracranial counterpart, suggesting the existence of benign forms of the disease. Surgical procedures should be weighed against the spontaneous resolution of the lesion.

Spinal cavernous angioma: a rare cause of subarachnoid hemorrhage.

A case of cervical intrathecal extramedullary cavernous angioma is presented. The rarity of this lesion in comparison with the more frequent vertebral cavernous angiomas with secondary extension to the epidural space is emphasized. The special features of this case are noted: the acute clinical onset due to recurrent subarachnoid hemorrhages, the visualization only by means of magnetic resonance imaging, and the unusual cervical level. The most debated characteristics of these lesions and the relevant literature are summarized.

Benign arterial dissections of the posterior circulation.

Four young adults with spontaneous dissection of the vertebrobasilar system are reported. Clinically, two patients presented with subarachnoid hemorrhage and two with brain-stem ischemia. In two cases of ruptured arterial dissection of the posterior cerebral artery, angiography demonstrated fusiform and "sausage-like" dilatation of the involved vessel. In two cases of occlusive dissection of the basilar artery, angiography revealed the typical "string sign." All four patients were treated conservatively: three survive in good clinical condition and one remains disabled. Follow-up angiograms showed spontaneous healing of the lesion with return to an almost normal arterial configuration in two cases; residual narrowing corresponding to the dissection was the most notable finding in the other two. It is recommended that, in a subset of neurologically stable patients, angiographic monitoring is undertaken to assess the tendency for spontaneous repair before surgical intervention is planned.

Ganglionic cysts of the peroneal nerve at the knee: CT and surgical correlation.

The CT appearance of two cases of ganglionic cysts of the common peroneal nerve at the knee is reported. In both cases the ganglion appeared as a cystic unenhanced lesion of mucoid density. The radiological findings were confirmed by surgery. The differences in the appearance of intraneural and extraneural ganglia are discussed.

Ulnar neuropathy due to a carpal ganglion: the diagnostic contribution of CT.

Clinical features and electrophysiologic studies indicated a lesion of the ulnar nerve in the wrist of a 50-year-old man. CT of this region revealed a ganglion inside Guyon's canal. Surgical exploration disclosed a carpal ganglion compressing the ulnar nerve just proximal to its division.

Long-term follow-up of occlusive cervical carotid dissection.

We retrospectively studied 19 cases of occlusive cervical carotid dissection encountered at our hospital between 1974 and 1984 and followed for 5-13 (mean 8.2) years to assess the long-term prognosis of the disease. Five patients had transient ischemic attacks, seven had minor stroke, six had major stroke, and one had epileptic seizures. Angiography demonstrated the typical string sign in 17 cases, a double lumen with occlusion in one, and multiple scalloped narrowings with distal occlusion in the other. Three patients died within 1 month and three remain severely disabled (overall mortality and major morbidity 32%), five have permanent deficits, and seven are neurologically intact; the remaining patient was lost to follow-up. Five patients were treated surgically (two had extracranial-intracranial bypass and three had cervical carotid exploration), and the other 14 were treated medically. The overall rate of reopening was 47% with eight of 10 patients demonstrating recanalization on control angiography and another patient demonstrating recanalization at surgery. These nine patients remain clinically stable on follow-up evaluations. However, vascular abnormalities in the healed arteries were notable and include kinking, fibromuscular dysplasia, dissecting aneurysms, intracranial occlusion, and a residual mural defect.

Extradural hematomas of the posterior cranial fossa. Observations on a series of 32 consecutive cases treated after the introduction of computed tomography scanning.

A series of 32 patients with posterior fossa epidural hematoma treated after the introduction of computed tomography scanning between 1975 and March 1988 is presented. Sixteen patients harbored "pure" epidural hematomas, whereas 16 had other infratentorial or supratentorial traumatic lesions. Glasgow Coma Scale on admission was 7 or less in 10 patients, 8-12 in 11, and 13-14 in 11. Only six patients had a lucid interval. Thirty patients were treated surgically; two patients with small hematomas were treated conservatively. Overall mortality was 15.6%, with 0% for "pure" and 31.2% for "complicated" posterior fossa epidural hematomas. The value of routine computed tomography scanning is emphasized in cases with occipital skull fracture or when such fracture is found in patients undergoing emergency evacuation of supratentorial hematomas. The pertinent literature is addressed with special regard to the delayed occurrence, associated lesions, and mortality of posterior fossa epidural hematomas and to the role of computed tomography scanning.

The growth of cerebral cavernous angiomas.

The natural history of cavernous angiomas is poorly understood, and their growth has rarely been documented. We report three cases of cavernous angiomas that grew to large size in 6 years, 2 years, and 2 months, respectively. An initial computed tomographic scan disclosed no abnormalities in one patient and demonstrated two "minimal" lesions in the other two. The mechanisms of growth of these lesions are discussed; subsequent hemorrhages and capsule formation played a major role in their enlargement.

Rapid spontaneous disappearance of an acute extradural hematoma: case report.

The authors report the case of a patient presenting with an acute extradural hematoma and diffuse axonal injury. Control CT scan performed 4 hours later showed the complete resolution of the extradural collection together with increased evidence of shearing injuries. The mechanism of the hematoma resolution may probably be related to the concomitant acute brain swelling.

Blunt traumatic carotid dissection with delayed symptoms.

We describe five patients with blunt traumatic carotid dissection with delayed clinical presentation that varied from 2 weeks to 6 months. Four patients had severe head injury, and one patient had direct blunt trauma to the neck. Cerebrovascular symptoms developed in four patients. The fifth patient suffered loss of vision as a result of a concurrent giant intracranial dissecting aneurysm. Arteriography demonstrated a "string sign" in two cases and a cervical carotid aneurysm in three; two of the latter also had siphon occlusion, and one of these had a superimposed supraclinoid dissecting aneurysm. One patient was treated by thromboendarterectomy, one by aneurysmorraphy, another by carotid ligation, and the other two patients were treated medically. Mechanisms of injury, forensic problems, and therapeutic options are discussed.