Fractionated Stereotactic Radiation Therapy for Pituitary Adenomas: An alternative escalating protocol of hypofractionated stereotactic radiotherapy delivering 35Gy in 5 fractions.

PURPOSE: Evaluate efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) for patients treated for pituitary adenoma (PA) with an alternative HSRT escalating protocol delivering 35Gy in 5 fractions. MATERIAL AND METHODS: From June 2007 to March 2017, 29 patients with pituitary adenoma were treated in Antoine Lacassagne Cancer Centre with an alternative HSRT protocol. Prescribed dose was 35Gy in 5 fractions of 7Gy. Radiographic responses were assessed by annual MRI. Hormone blood samples were evaluated each year after HSRT. RESULTS: A total of 29 patients aged between 23 and 86 years (median 54 years) were included. Twelve patients received HSRT for recurrent cases and 12 received postoperative adjuvant HSRT, 5 patients did not have surgery. After a median follow-up period of 47 months local control rate was 96%. One patient presented an out-field tumor regrowth 73 months after HSRT. The majority of PA were endocrine-active (18 patients, 62%). After HSRT, 8 patients (44%) presented complete response on initial secretion, 4 patients (23%) presented partial response on initial secretion. Four patients (14%) presented grade 2 or more acute radiation toxicities. One grade 4 visual disorder was observed for one patient. CONCLUSIONS: HSRT delivering 35Gy in 5 fractions represents a feasible treatment and shows promising results to reduce hormonal overproduction and to improve local control in PA.

[Coordination of health vigilances: for a global management of hospital risks]. / La coordination des vigilances sanitaires : pour une gestion plus globale des risques hospitaliers.

The sanitary vigilances represent a permanent sanitary surveillance. They signal, enregister, treat and investigate the adverse events occurring through the use of health products. They assure the traceability of these health products and the management of the sanitary alerts. The sanitary vigilances are part of the sanitary security. They are optimized when coordinated and integrated to the global risk management process of the health care establishments.

[Oculoplastic complications of the excision of meningiomas with orbital extension]. / Complications oculoplastiques de l'exérèse des méningiomes à extension orbitaire.

INTRODUCTION: Meningiomas with orbital extension are the most frequent benign orbital tumors. The few studies available on the postoperative complications of their excision focus on the postoperative evolution of proptosis, visual acuity and visual field deficits. The goal of our study was to highlight the oculoplastic complications secondary to their excision. MATERIAL AND METHOD: We identified all cases of meningiomas with orbital extension undergoing excision either neurosurgically or via an orbital approach in the ophthalmology and neurosurgery departments of Pasteur university medical center in Nice between February 2011 and January 2017. The data collection included the postoperative presence of proptosis, oculomotor disturbance, lid disorders, dry eye and trigeminal nerve damage. RESULTS: Twenty-nine patients were included; 89.7 % were women. The mean age was 55 years. Postoperative complications included 25 % residual proptosis; 40.7 % oculomotor disturbance, 75 % of which regressed at least partially; 50 % ptosis, 21 % of which did not regress; 40 % dry eye; and in 21.4 % the trigeminal nerve was involved. CONCLUSION: The management of meningiomas with orbital extension is difficult due to their anatomical location and requires joint neurosurgical and oculoplastic management. Sufficient follow-up is required before recommending surgery for oculomotor disturbances. The frequency of occurrence of ptosis with potential recommendation for surgery requires caution given the occurrence of trigeminal nerve involvement and dry eye syndrome.

DOCK4 promotes loss of proliferation in glioblastoma progenitor cells through nuclear beta-catenin accumulation and subsequent miR-302-367 cluster expression.

Glioblastomas (GBM) are lethal primitive brain tumours characterized by a strong intra-tumour heterogeneity. We observed in GBM tissues the coexistence of functionally divergent micro-territories either enriched in more differentiated and non-mitotic cells or in mitotic undifferentiated OLIG2 positive cells while sharing similar genomic abnormalities. Understanding the formation of such functionally divergent micro-territories in glioblastomas (GBM) is essential to comprehend GBM biogenesis, plasticity and to develop therapies. Here we report an unexpected anti-proliferative role of beta-catenin in non-mitotic differentiated GBM cells. By cell type specific stimulation of miR-302, which directly represses cyclin D1 and stemness features, beta-catenin is capable to change its known proliferative function. Nuclear beta-catenin accumulation in non-mitotic cells is due to a feed forward mechanism between DOCK4 and beta-catenin, allowed by increased GSK3-beta activity. DOCK4 over expression suppresses selfrenewal and tumorigenicity of GBM stem-like cells. Accordingly in the frame of GBM median of survival, increased level of DOCK4 predicts improved patient survival.

Treatment of newly diagnosed symptomatic pure low-grade oligodendrogliomas with PCV chemotherapy.

Based on studies relating to anaplastic oligodendroglioma (OG) chemosensitivity and benefit of time to progression or overall survival, chemotherapy for pure OG has been proposed. Several studies have reported the efficacy of various chemotherapeutic agents in a small number of patients with low-grade gliomas, e.g. pure astrocytomas, OG or mixed histologies. The 5-year survival rate varies from 61% to 89% with a mean time to progression of 5 years. We report the outcome of 33 consecutive patients with pure low-grade OG diagnosed between 1990 and 2006 systematically treated for residual or non-removable tumor with PCV chemotherapy regimen as the front-line treatment after surgery. All the tumors were low grade (grade II) pure OG according to the WHO classification. All patients were symptomatic at presentation and underwent neurosurgical procedure for histological diagnosis. Response was evaluated by clinical assessment and brain magnetic resonance imaging. Twenty-one men and 12 women with a mean age at pathological diagnosis of 46.5 years were studied. The most common first symptom was partial epileptic seizure (73.7%). Six patients (18%) had initial gadolinium enhancement, associated with methoxyisobutyl (MIBI) hypermetabolism (P < 0.001). The resection was partial in seven cases (21%), and 26 patients (79%) had biopsy only. Eleven patients (36%) had a malignant transformation during the follow-up with a median time to progression of 19 months. Favorable prognostic factors were lack of contrast enhancement (P < 0.0001), and age <40 years (P < 0.0003); 90% of patients were progression-free at 1 year. Survival rates at 2, 5 and 10 years were 85%, 75% and 50%, respectively. Up-front chemotherapy with PCV regimen is a good treatment for symptomatic pure low-grade OG, as it increases the number of progression-free patients and time to progression. These results suggest that radiotherapy could be postponed until the malignant transformation occurs to delay cognitive side effects of irradiation.

[Effectiveness of adjuvant corticosteroid therapy for chronic subdural hematoma: a retrospective study of 198 cases]. / Efficacité de la corticothérapie dans le traitement adjuvant des hématomes sous-duraux chroniques. Etude rétrospective sur 198 cas.

BACKGROUND AND PURPOSE: Adjuvant treatments can be proposed in addition to surgery for patients with chronic subdural hematoma (CSDH) in order to improve the postoperative outcome. According to the survey published in 2001 by the Neurosurgery French Society, 38% of French neurosurgeons use adjuvant corticosteroid therapy after surgery. Does this adjuvant corticosteroid therapy have an effect on the postoperative outcome of CSDH? METHODS: A retrospective trial was performed on patients who were surgically treated for CSDH between January 1998 and July 2002 in the Nice Department of Neurosurgery. Corticosteroid therapy was initiated just after surgery and maintained for one month. Part of the patients were not given corticosteroids enabling a comparison of two groups: "corticosteroid therapy" versus "no corticosteroid therapy". RESULTS: One hundred and ninety-eight patients were included in the trial, 142 patients in the "corticosteroid therapy" group and 56 patients in the "no corticosteroid therapy" group. The difference in survival between the two groups was significant in favor of the group give corticosteroids. A multivariate analysis was carried out which confirmed the beneficial effect of the corticosteroid therapy on survival of the operated patients. Their risk of death was threefold less than those not given this treatment (p=0.006). CONCLUSIONS: This study highlighted a protective effect of postoperative corticosteroid therapy on patient survival. This effect persisted at multivariate analysis. However, due to skews inherent in retrospective studies, a multicentric prospective randomized trial is being prepared in our institution to confirm these results.

[Subthalamic nucleus stimulation using a Fisher ZD stereotactic frame, MR-CT fusion guidance and peroperative orthogonal radiographs, in Parkinson disease]. / Evaluation de la stimulation du noyau sous-thalamique utilisant un cadre de Fischer adapté, un guidage par fusion IRM-scanner et un contrôle radiographique stéréotaxique peropératoire, dans la maladie de Parkinson.

BACKGROUND: We present the method and results of an original technique to implant electrodes in the subthalamic nucleus (STN) to treat Parkinson's disease, based on adaptations of the Fisher ZD stereotactic frame. METHODS: Targets coordinates were calculated after fusion of stereotactic CT-scan and MRI images. STN was localized by its theoretical coordinates according to AC-PC and by its direct visualization on T2 images. Electrodes were implanted after local anesthesia, using peroperative multicanal microrecordings and test stimulation. Electrodes location was checked by peroperative perpendicular radiographs. To avoid projection of the frame arm on the area of interest on anteroposterior and lateral radiographs, the arm was fixed at 45 degrees from the usual 90 degrees position. This original fixation needed a trigonometric transformation of the X and Y stereotactic coordinates. Radiopaque markers, fixed on the frame, were identified on the radiographs, allowing the calculation of the stereotactic coordinates of the electrode tip, which were then entered in the stereotactic MRI, to check its location from the defined target. RESULTS: No problem due to adaptations of the frame occurred in the 60 patients. In all cases, peroperative radiographs allowed to confirm the correct location of electrodes. Six months after surgery, UPDRS III score without medication was decreased by 52% with stimulation "on". UPDRS IV items 32, 33 and 39 scores were decreased by 75,7, 79,5 and 72%. Daily dopa-equivalent dose was decreased by 71%. One asymptomatic thalamic hematoma and two wound infections occurred. CONCLUSION: This method was efficient and safe to implant deep electrodes.

Cerebral vasospasm after transsphenoidal surgery for pituitary adenoma: Case report and review of the literature.

INTRODUCTION: Cerebral vasospasm (CVS) is a rare complication of transsphenoidal surgery for pituitary adenomas. CASE REPORT: The authors describe a symptomatic cerebral ischemia due to an internal carotid, left middle cerebral artery and anterior cerebral artery vasospasm in a patient undergoing transsphenoidal surgery for a pituitary macro adenoma. The patient was successfully treated by an endovascular balloon angioplasty. CONCLUSION: This issue should be taken into account, even when rare, in every patient who has surgery for a pituitary tumor, particularly when it concerns a large macro adenoma with suprasellar extension. Special precautions must be taken to avoid this rare complication.

Spinal cord compression due to a primary vertebral hydatid disease: A rare case report in metropolitan France and a literature review.

INTRODUCTION: Bone echinococcosis or bone hydatidosis is mainly caused by the larva of a dog taenia, Echinococcus granulosus. We described a rare imported case in metropolitan France of spinal cord compression from a primary vertebral hydatidosis. CASE: A 25-year-old woman, native of a rural area in the South of Romania, was admitted for backache and slight weakness of both legs. Radiological findings showed a paravertebral pluricystic lesion invading the spinal canal with spinal cord compression at the T9 level, without associated visceral localization. We performed an urgent surgical decompression using a posterior approach. The whole extradural cysts were carefully excised with irrigation of the cystic fluid with hypertonic saline. Treatment was completed with long-term anti-parasitic chemotherapy. DISCUSSION: Bone echinococcosis is rare and represents about 2% of hydatidosis. The spine localization is found in half of the cases. This pathology particularly occurs in the Eastern and Southern countries of Mediterranean sheep breeding areas, but still rare in metropolitan France. Spinal cord compression is a frequent presentation of spinal hydatidosis but neurological symptoms are various and non-specific. The reference treatment is removal surgery with particular precautions, followed by an anti-parasitic chemotherapy (albendazole) to limit recurrences. However, a long-term follow-up is mandatory due to later recurrences.

Epidermal growth factor receptor and labeling index are independent prognostic factors in glial tumor outcome.

The aim of this study was to perform a multivariate analysis including clinical and biological prognostic factors on glial tumor outcome. Seventy-nine patients were analyzed (48 men and 31 women; mean age = 56 years, range = 16-77 years): 7 had a benign glial tumor (grades 1 and 2), 21 had an anaplastic glial tumor (grade 3), and 51 had a glioblastoma (grade 4). Median follow-up was 17.9 months for patients who survived (50 patients died). Biopsies were obtained at time of diagnosis (complete tumor resection in 62 patients and stereotaxic biopsies in 17 patients). Epidermal growth factor receptor (EGFR) was measured by a binding assay, and labeling index (LI) was measured by tritiated thymidine incorporation. EGFR varied from 4 to 73,110 fmol/mg protein (mean = 3912 fmol/mg protein; median = 374 fmol/mg protein; n = 79). LI varied between 0.1 and 16.5% (mean = 6.2%; median = 5.2%; n = 40). Log10 EGFR was significantly and positively correlated with patient age. LI was significantly different according to tumor histology. Univariate Cox analysis (end point was cancer death) showed that age (P = 0.027), log10 EGFR (P = 0.025), and LI (P = 0.0019) were significant continuous variables, the survival being shortened when the covariable increased; tumor resection (P = 0.015, relative risk = 0.45) and histology (P = 0.0009) were significant categorical factors. A multivariate Cox analysis (forward selection) including age, histology, tumor resection, log10 EGFR, and LI revealed that log10 EGFR, LI, and tumor resection were the only independent significant predictors of survival. This multivariate approach reveals that the clinical prognostic factors of glial tumors, namely age and tumor histology, disappear, to the benefit of intrinsic characteristics of the tumor, i.e., EGFR expression and LI, suggesting that coupled EGFR and LI determination could be a useful tool for better evaluation of glial tumor outcome.

[Stabwound of the cervical spinal cord. Two case reports]. / Plaie médullaire cervicale par arme blanche. Présentation de deux cas.

Two cases of Brown-Sequard syndrome following a stab wound of the cervical spinal cord are reported. Spinal cord hemisection was confirmed by magnetic resonance imaging and surgical exploration. Both patients presented leakage of the cerebrospinal fluid and underwent surgical repair. In the first case, the pia-mater was sutured to close the wound and decrease the risk of post-traumatic syringomyelia. Outcome at ten and two years follow up was good in both patients who were able to walk. One of them returned to work. The contribution of surgical repair of spinal cord stab wounds and mechanisms of recovery are discussed.

Endovascular treatment of ruptured intracranial aneurysms in patients aged 65 years and older: follow-up of 52 patients after 1 year.

BACKGROUND AND PURPOSE: We sought to describe the clinical outcome and results obtained in the endovascular therapy of ruptured cerebral aneurysms in the elderly over an 8-year period. We compared endovascular therapy results in patients aged > or =65 and <65 years. METHODS: During 1993-1999, 52 patients aged 65 to 85 years (mean age, 71.5+/-4.7 years) were embolized with the use of Guglielmi detachable coils (group I). During the same period, 143 patients aged <65 years (mean age, 47+/-11 years) with ruptured cerebral aneurysm were treated with the same technique (group II). A clinical assessment was made on admission with the Hunt and Hess (HH) classification and again in the 12th month with the Glasgow Outcome Scale (GOS), with arteriographic control in months 3 and 12. RESULTS: In group I, clinical grades on admission were as follows: HH 1, 9.5%; HH 2, 33%; HH 3, 21%; HH 4, 34.5%; HH 5, 2%. Outcome was favorable in 48% of patients (GOS 1 or 2); the mortality rate was 23%. No rebleeding was observed. Patients presenting lesions > or =10 mm had an unfavorable outcome in >77% of cases. Thromboembolic complications were present in 13% of cases. In group II, clinical grades on admission were as follows: HH 1, 14.5%; HH 2, 47%; HH 3, 11%; HH 4, 24%; HH 5, 3.5%. Favorable outcome (GOS 1 or 2) was observed in 77% of cases, with 14% mortality. Complications due to the endovascular procedure were present in 4.2% of cases. Patients with HH grades 1 or 2 on admission showed a positive outcome (GOS 1 or 2) in 77% of cases in group I and in 88.5% of cases in group II. Mortality was 9% in the first subgroup compared with 2.8% in the second. Patients who had a high clinical grade on admission (HH 4 or 5) showed a favorable outcome (GOS 1 or 2) in 16% of cases in group I compared with 41% in group II. CONCLUSIONS: Endovascular treatment of ruptured intracranial aneurysms in patients aged > or =65 years appears to be effective against rebleeding and represents an alternative to surgery. However, perioperative thromboembolic complications are more frequent in the elderly population.

Expression of vascular endothelial growth factor-b in human astrocytoma.

Growth of human malignant gliomas is stringently dependent on an angiogenic process that probably involves vascular endothelial growth factor (VEGF). Expressions of mRNA coding for the different forms of VEGF were analyzed in surgical specimens from human astrocytomas. Low levels of placental growth factor (PGF) and VEGFC mRNA were observed in polymerase chain reaction, but not in Northern blot experiments. VEGF mRNA was found in some but not all grade and grade IV astrocytomas. VEGFB mRNA was observed in all tissue samples analyzed irrespective of the tumor grade. A new splice variant of VEGFB (VEGFB155) that lacks exons 5 and 6 is described. Expressions of VEGF mRNA in cultured glioblastomas cells were upregulated by hypoxia, but the sensitivity of the cells to hypoxia was reduced as compared with normal rat astrocytes. VEGF expression was depressed by dexamethasone. Expressions of VEGFB mRNA were affected neither by hypoxia nor by dexamethasone. The results indicate a coexpression of VEGF mRNA and VEGFB mRNA in human astrocytomas. Expression of VEGFB is markedly different from that of VEGF. Possible roles of VEGFB as a cofactor for hypoxia-induced angiogenesis in human astrocytomas are discussed.

Beam collimation and bolusing material optimizations for 10boron neutron capture enhancement of fast neutron (BNCEFN): definition of the optimum irradiation technique.

PURPOSE: In boron-10 neutron capture enhancement of fast neutron irradiation (BNCEFN), the dose enhancement is correlated to the 10B concentration and thermal neutron flux. A new irradiation technique is presented to optimize the thermal neutron flux. METHODS AND MATERIALS: The coupled FLUKA and MCNP-4A Monte Carlo codes were used to simulate the neutron production and transport for the Nice and Orleans facilities. RESULTS: The new irradiation technique consists of a 20-cm lead blocks additional collimator, placed close to the patient's head, which is embedded in a pure graphite cube. A 24-fold thermal neutron flux increase is calculated between a 5 x 5 cm2 primary collimated field, with the patient's head in the air, and the same field size irradiated with the optimum irradiation technique. This increase is more important for the p(60)+Be Nice beam than for the p(34)+Be Orleans one. The thermal neutron flux is 2.1 x 10(10) n(th)/Gy for each facility. Assuming a 100 microg/g 10B concentration, a physical dose enhancement of 22% is calculated. Moreover, the thermal neutron flux becomes independent of the field size and the phantom head size. CONCLUSION: This technique allows conformal irradiation of the tumor bed, while the thermal neutron flux is enhanced, and spreads far around the tumor.

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.

Fluorescence in situ hybridization study of aneuploidy of chromosomes 7, 10, X, and Y in primary and secondary glioblastomas.

The aneuploidy of autosomes 7, 10, and sex chromosomes (X and Y) was analyzed in a series of 44 primary (de novo) and 20 secondary glioblastomas using fluorescence in situ hybridization (FISH) on smear preparations of glioma tissue. The tumors were screened for trisomy 7, monosomy 10, as well as loss of the Y chromosome and disomy of the X chromosome in male subjects, and monosomy of the X chromosome in female subjects. We found that taken alone or in combination, these chromosomal abnormalities do not appear to be characteristic of a glioblastoma subtype; therefore, they do not allow the differentiation between primary and secondary glioblastomas. Also, the loss of a chromosome 10 appears to be an earlier event than a gain of a chromosome 7 for the genesis of a secondary glioblastoma.

Cytogenetics of malignant gliomas. II. The sex chromosomes with reference to X isodisomy and the role of numerical X/Y changes.

Sex chromosomal monosomy with total loss of an X or Y is frequently observed in malignant gliomas. Beyond that, not much is known about the behavior of the sex chromosomes in these tumors. We noted loss of the X from 3 of 13 gliomas from women (23%) compared to loss of the Y from 16 of 28 gliomas from men (57%). There were two structural rearrangements of the Y (an inversion and a translocation with chromosome 4). Most unexpectedly, clones with sex chromosome reversal were encountered in 3 cases. These XX clones in gliomas from men are perforce the consequence of Y loss coupled with X isodisomy, a nonrandom sequence of sex chromosome changes. We examined the company kept by numerical X and Y changes in clones and found that clones with numerical sex chromosome changes had fewer autosomal abnormalities, reflecting a distinct tendency to clonal separation of sex chromosome from autosomal abnormalities. We conclude that the sex chromosome changes are not a necessary part of the neoplastic process in malignant gliomas but that they must be of biologic significance to the brain since they are highly nonrandom in frequency, type, and sequence in brain cells.

Nontraumatic spinal epidural hematoma: report of four cases and review of the literature.

OBJECTIVE AND IMPORTANCE: Spontaneous spinal epidural hematoma is a rare entity. We report four cases of nontraumatic spinal epidural hematomas observed from 1990 to 1994. CLINICAL PRESENTATION: In two cases, the causes were determined to be an acquired coagulopathy and a vascular malformation; in the other two cases, no causes were detected. We reviewed 85 cases in the literature, with particular emphasis on the various causes detected (coagulopathy, vascular malformations, tumor) and the diagnostic methods used. INTERVENTION: All the patients were investigated by computed tomography and magnetic resonance imaging and underwent surgery. CONCLUSION: We considered the expression "nontraumatic epidural hematoma" to be less ambiguous than "spontaneous spinal epidural hematoma," which is the one that is usually used in the literature and corresponds to various definitions. In the absence of any signs suggestive of vascular malformation on magnetic resonance imaging, preoperative angiography is not essential and need not delay the surgical procedure, because the timing of the surgery, together with the preoperative clinical state, determines the quality of the clinical result.

Occipitocervical fixation using hooks and screws for upper cervical instability.

OBJECTIVES: Occipitocervical fixation is used for the treatment of nontraumatic upper cervical instabilities. To date, plates have been fixed with screws or wires. However, these devices are not indicated in the treatment of patients with severe osteoporosis or in instances of significant thinning of the occipital bone. We performed a clinical trial of a new type of fixation that uses cervical interlaminar hooks and occipital claws with hooks or with screws (CCD type; Sofamor-Danek, Roissy, France) for the treatment of nontraumatic upper cervical instabilities. METHODS: Five women and one man ranging in age from 28 to 72 years (average age, 54 yr) were thus treated. The CCD type material had two rod plates and hooks allowing the proper placement of interlaminar and occipital claws. The occipital plate can also be directly screwed to the bone. Occipital hooks were used in four patients. The other two patients, who had occipitocervical congenital abnormalities that required an occipitocervical opening and an additional dural enlargement, underwent occipital screw fixation because of the previous opening of the foramen magnum. A cancellous iliac autograft allowed the usual fusion. RESULTS: No postoperative complications were observed, and all patients experienced significant improvement of their neck pain. Four patients had neurological symptoms. The condition of two patients improved, and the condition of the other two stabilized. CONCLUSION: This report confirms the interest of the CCD method to correct all types of upper cervical instabilities, even in cases of unusual thinning of the occipital bone or in osteoporotic states.

Chiari Type I malformation and syringomyelia in unrelated patients with blepharophimosis. Report of two cases.

Syringomyelia is a rare, mainly sporadic disease of the spinal cord, which is associated with 80% of cases in which a Chiari Type I malformation is also present. A mendelian transmission of syringomyelia (autosomal dominant or recessive) has been proposed in approximately 2% of reported cases. The association of syringomyelia with hereditary diseases (Noonan's syndrome, phacomatoses) has been mentioned frequently in the literature. The authors report the presence of a Chiari Type I malformation accompanied by syringomyelia in two unrelated patients affected by a familial Type II blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). The first patient was a 35-year-old woman who presented with a right C-8 root paresia. The second case involved a 20-year-old man who complained of cervical radicular pain. Both belong to families in which BPES was segregated in an autosomal dominant modality, but other family members had no known neurological symptoms. To the authors' knowledge, such a combination has never been described. Perhaps the possible involvement of a genetic component in some cases of Chiari Type I-associated syringomyelia will someday be debated.