Metabolomic characterization of human hippocampus from drug-resistant epilepsy with mesial temporal seizure.

OBJECTIVE: Within a complex systems biology perspective, we wished to assess whether hippocampi with established neuropathological features have distinct metabolome. Apparently normal hippocampi with no signs of sclerosis (noHS), were compared to hippocampal sclerosis (HS) type 1 (HS1) and/or type 2 (HS2). Hippocampus metabolome from patients with epilepsy-associated neuroepithelial tumors (EANTs), namely, gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs), was also compared to noHS epileptiform tissue. METHODS: All patients underwent standardized temporal lobectomy. We applied 1 H high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy to 48 resected human hippocampi. NMR spectra allowed quantification of 21 metabolites. Data were analyzed using multivariate analysis based on mutual information. RESULTS: Clear distinct metabolomic profiles were observed between all studied groups. Sixteen and 18 expected metabolite levels out of 21 were significantly different for HS1 and HS2, respectively, when compared to noHS. Distinct concentration variations for glutamine, glutamate, and N-acetylaspartate (NAA) were observed between HS1 and HS2. Hippocampi from GG and DNT patients showed 7 and 11 significant differences in metabolite concentrations when compared to the same group, respectively. GG and DNT had a clear distinct metabolomic profile, notably regarding choline compounds, glutamine, glutamate, aspartate, and taurine. Lactate and acetate underwent similar variations in both groups. SIGNIFICANCE: HRMAS NMR metabolomic analysis was able to disentangle metabolic profiles between HS, noHS, and epileptic hippocampi associated with EANT. HRMAS NMR metabolomic analysis may contribute to a better identification of abnormal biochemical processes and neuropathogenic combinations underlying mesial temporal lobe epilepsy.

Atonic seizures in children with surgically remediable epilepsy: a motor system seizure phenotype?

Atonic seizures are common in some epileptic syndromes beginning in infancy or early childhood but they are rarely described in epilepsy with focal seizures of structural aetiology. We aimed to characterize the electroclinical features of atonic seizures in surgically remediable paediatric patients and to study the spatiotemporal organization of the underlying epileptogenic networks. We retrospectively analysed two consecutive, longitudinally evaluated and surgically treated paediatric patients presenting with atonic seizures as a manifestation of pharmacoresistant epilepsy of structural aetiology, evidenced by scalp- and stereotactic intracerebral video-EEG-recordings. A quantitative analysis of the epileptogenic zone organization was performed using the "epileptogenicity index". Long-lasting generalized ictal atonia, occurring in infancy, was a predominant clinical feature in both patients, with some hints of focal origin present in one case. The seizure phenotype evolved at later age into subtle segmental atonia, associated with prominent positive motor signs. The epileptogenic zone was localized within the dorsolateral or mesiolateral premotor region. Its spatial organization was focal, matching the lesional cortex in one and distributed involving several lesional and non-lesional structures in the other case. The emergence of atonic semiology temporally correlated with involvement of both lateral and mesial premotor, as well as primary motor areas. We hypothesize that atonic seizures may be considered as a motor system seizure phenotype in the setting of structural epilepsy. Complete removal of the epileptogenic area provided excellent seizure control.

Balloon protection of the Labbé vein during transarterial embolization of a dural arterio-venous fistula.

INTRODUCTION: Endovascular treatment of type III dural arterio-venous fistulas can be challenging if the fistulous point is close to a functionally important cortical vein. METHODS: A technique is described for temporary balloon protection of the vein of Labbé during transarterial Onyx embolization of a type III dural arterio-venous fistula. One illustrative case is presented. Careful anatomic consideration of the concerned venous segment (at the insertion point into the lateral sinus) and the choice of balloon minimized the risk of venous rupture. RESULTS: Using this method, satisfactory progression of Onyx was obtained within the arterio-venous shunt while preserving the patency of the Labbé vein. CONCLUSION: Temporary balloon protection of the Labbé vein is a feasible option to preserve its patency during embolization of dural arterio-venous fistulas. To the authors' knowledge, this is the first report on the use of temporary balloon protection of a cortical vein.

Giant postsurgical pseudomeningocele by SPECT/CT cisternography.

We describe a case of a 32-year-old man with a giant pseudomeningocele seen on MRI examination 6 months after spinal surgery. Radionuclide SPECT/CT cisternography performed after intrathecal suboccipital injection of In-DTPA identified the site of cerebral spinal fluid leak at the L4 level, and the patient underwent surgical correction of the dural defect. A repeat MRI examination 8 months later showed no signs of recurrence.

Surgical management of spinal dural arteriovenous fistulas.

Spinal dural arteriovenous fistulas are the most common type of spinal arteriovenous malformations. Treatment options consist of microsurgical exclusion and/or endovascular embolization. We retrospectively identified all patients who benefited from surgical treatment at our tertiary center between January 2001 and December 2008. Clinical and imaging data were collected from patient files, including pre- and post-operative formal neurological examination, complete spine MRI and spinal digital subtraction angiography. Of our 30 patients, 25 were men and five were women with a median age of 62 years (range 24-76). The average delay between symptom onset and clinical diagnosis was 27 months (range 1-90). Complete cure of the fistula was obtained in all patients in a single surgical session with no procedural complications and no surgical morbidity. After a mean follow-up period of 32 months (range 14-128), 25 patients (83%) had improved, four were stable and one worsened. Despite recent advances in endovascular techniques and materials, there is a subgroup of patients for which surgery remains the best treatment option. Careful patient selection, a multidisciplinary approach and standardized surgical techniques can lead to excellent results with virtually no complications.

Flow control using Scepter™ balloons for Onyx embolization of a vein of Galen aneurysmal malformation.

PURPOSE: We present a technical development of the endovascular treatment technique for vein of Galen aneurysmal malformation, using Onyx™ (ethylene vinyl alcohol copolymer) delivered under flow control through double-lumen balloon microcatheters. MATERIALS AND METHODS: An 11-month-old patient that initially presented with increasing head circumference was diagnosed with mural type vein of Galen aneurysmal malformation. Complete cure was obtained in a single endovascular treatment session. Onyx was delivered simultaneously through two double-lumen balloon microcatheters (Scepter™, Microvention, Terumo Group). In both arterial feeders, balloon inflation occluded the high-flow arterial-venous shunting and thus facilitated the controlled propagation of the embolic product in the afferent artery and the shunt point while preventing distal migration into the venous system. RESULTS: Two years post-procedure, MR imaging showed persistent occlusion of arterial-venous shunts with complete regression of the venous dilatation. On clinical examination, the patient had no neurological deficits, and no cognitive impairment was detected at neuropsychological testing. CONCLUSION: The use of double-lumen balloon microcatheters for flow control during delivery of Onyx represents a viable alternative for the endovascular treatment of vein of Galen aneurysmal malformations.

Neural tube defects: the experience of the registry of congenital malformations of Alsace, France, 1995-2009.

CONTEXT AND OBJECTIVE: Considering the lack of accurate and up-to-date information available about neural tube defects (NTDs) in France, the purpose of this study was to review clinical and epidemiological data of NTDs and to evaluate the current efficiency of prenatal diagnosis in Alsace (northeastern France). METHODS: A population-based retrospective study was performed from data of the Registry of Congenital Malformations of Alsace between 1995 and 2009. Data were analyzed as a whole and according to the anatomical type of the malformation (anencephaly, cephalocele and spina bifida). Statistical analyses were carried out using the Statistical Package for the Social Sciences. RESULTS: 272 NTDs were recorded divided in 113 cases of anencephaly (42%), 35 cases of cephalocele (13%) and 124 cases of spina bifida (45%). The total prevalence at birth of 14/10,000 (95% CI 13-16) was stable throughout the reporting period. A chromosome abnormality was identified in 27 cases (12% of all karyotyped cases). NTDs were prenatally diagnosed by ultrasound in 88% of the cases. The mean age upon prenatal diagnosis slightly declined during the 15-year period, significantly for spina bifida only. The global rate of terminations of pregnancy following prenatal diagnosis was 97% (230/238). CONCLUSION: This work constitutes a unique population-based study providing accurate and specific up-to-date data from a unique center over a longer period (1995-2009). The most important information concerns the high and stable prevalence, which calls into question the efficiency of the primary prevention by folic acid supplementation and the efficiency of prenatal diagnosis.

Posterior atlanto-occipital and atlanto-axial area and its surgical interest.

UNLABELLED: Classic anatomical studies describe two membranes - atlanto-occipital and atlanto-axial in the posterior aspect of the craniocervical region. During many surgical procedures in this area, however, we have not found such membranes. OBJECTIVE: To clarify the anatomical aspects and structures taking part of the posterior atlanto-occipital and atlanto-axial area. METHOD: Analysis of histological cuts of three human fetuses and anatomical studies of 8 adult human cadavers. RESULTS: In both atlanto-occipital and atlanto-axial areas, we have observed attachment between suboccipital deep muscles and the spinal cervical dura. However, anatomical description of such attachments could not be found in textbooks of anatomy. CONCLUSION: Our study shows the absence of the classical atlanto-occipital and atlanto-axial membranes; the occipito-C1 and C1-C2 posterior intervals are an open area, allowing aponeurotic attachment among cervical dura mater and posterior cervical muscles.

Posterior atlanto-occipital and atlanto-axial area and its surgical interest / Interesse cirúrgico da junção atlanto-occipital e atlanto-axial

Classic anatomical studies describe two membranes – atlanto-occipital and atlanto-axial in the posterior aspect of the craniocervical region. During many surgical procedures in this area, however, we have not found such membranes. Objective To clarify the anatomical aspects and structures taking part of the posterior atlanto-occipital and atlanto-axial area. Method Analysis of histological cuts of three human fetuses and anatomical studies of 8 adult human cadavers. Results In both atlanto-occipital and atlanto-axial areas, we have observed attachment between suboccipital deep muscles and the spinal cervical dura. However, anatomical description of such attachments could not be found in textbooks of anatomy. Conclusion Our study shows the absence of the classical atlanto-occipital and atlanto-axial membranes; the occipito-C1 and C1-C2 posterior intervals are an open area, allowing aponeurotic attachment among cervical dura mater and posterior cervical muscles. .

Em livros clássicos de anatomia é referida a existência de duas membranas, atlanto-occipital e atlanto-axial, participando do fechamento da região cranio-cervical. Entretanto, em frequentes procedimentos cirúrgicos que envolvem esta região, jamais detectamos a presença de tais membranas. Objetivo Estudar os aspectos anatômicos e as estruturas que participam do fechamento posterior dos espaços atlanto-occipital e atlanto-axial. Método Estudo de cortes histológicos de três fetos humanos e estudos anatômicos em 8 cadáveres humanos adultos. Resultados Em ambos os espaços, atlanto-occipital e atlanto-axial, encontramos uma aderência entre as estruturas musculares profundas e a dura-mater, sem as membranas atlanto-occipital e atlanto-axial descritas nos livros clássicos de anatomia. Conclusão Não foram encontradas as membranas atlanto-occipital e atlanto-axial no material estudado; os espaços atlanto-occipital e atlanto-axial são abertos permitindo expansões aponeuróticas entre os músculos profundos e a dura-mater. .

Endovascular treatment in two cases of bilateral ischemic stroke.

Acute bilateral intracranial large artery occlusion is a rare occurrence that can lead to bihemispheric ischemia and potentially devastating functional consequences. We discuss two cases that initially presented with unilateral symptoms and did not show signs of bilateral arterial occlusions on the initial MRI imaging. This became evident while performing the angiographic study at the beginning of the endovascular procedure. Both patients were successfully treated with bilateral mechanical thrombectomy as a complement to intravenous thrombolysis. We describe our method of simultaneous sequential bilateral thrombectomy. To our knowledge, this is the first report of successful endovascular therapy in bilateral ischemic stroke.

Endoscopic endonasal approach in the management of skull base chordomas--clinical experience on a large series, technique, outcome, and pitfalls.

Skull base chordomas represent very interesting neoplasms, due to their rarity, biological behavior, and resistance to treatment. Their management is very challenging. Recently, the use of a natural corridor, through the nose and the sphenoid sinus, improved morbidity and mortality allowing also for excellent removal rates. Prospective analysis of 54 patients harboring a skull base chordoma that were managed by extended endonasal endoscopic approach (EEA). Among the 54 patients treated (during a 72 months period), 21 were women and 33 men, undergoing 58 procedures. Twenty-two cases (40%) were recurrent and 32 (60%) newly diagnosed chordomas. Among the 32 newly diagnosed chordomas, a gross total resection was achieved in 28 cases (88%), a near total (>95% of tumor) in 2 cases (6%), a partial (>50% of tumor) in 2 cases (6%). Among the 22 recurrent chordomas, resection was complete in 7 cases (30%), near total in 7 (30%), and partial in 8 (40%). The global gross total resection rate was 65% (35/54 cases). Four patients (11%) recurred and 4 (11%) progressed within a mean follow-up of 34 months (range 12-84 months). Four patients (11%) were re-operated; one patient (1.8%) died due to disease progression, one patient (1.8%) died 2 weeks after surgery due to a massive bleeding from an ICA pseudo aneurysm. CSF leakage occurred in four patients (8%), and meningitis in eight cases (14%). No new permanent neurological deficit occurred. The EEA management of skull base chordomas requires a long and gradual learning curve that once acquired offers the possibility of either similar or better resection rates as compared to traditional approaches while morbidity is improved.

Hypothalamic hamartoma: is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis.

Gelastic seizures associated with hypothalamic hamartomas (HHs) are a clinicoradiologic syndrome presenting with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, electroencephalography (EEG) abnormalities, precocious puberty, behavioral disturbances, and progressive cognitive deterioration. Surgery in adults provides seizure freedom in only one third of patients. The poor results of epilepsy surgery could be explained by an extrahypothalamic epileptogenic zone. The existence of an independent, secondary epileptogenic area with persistent seizures after resection of the presumably primary lesion supports the concept of a "hypothalamic plus" epilepsy. "Hypothalamic plus" epilepsy could be related to either an extrahypothalamic structural lesion (visible on magnetic resonance imaging [MRI] or on neuropathology) or if the former is absent, to a functional alteration with enhanced epileptogenic properties due to a process termed secondary epileptogenesis. We report two patients with gelastic seizures with HH (gelastic seizures isolated or associated with dyscognitive seizures of temporal origin). Both patients underwent two-step surgery: first an endoscopic resection of the HH, followed at a later time by temporal lobectomy. Both patients became seizure-free only after the temporal lobectomy. In both cases, neuropathology failed to demonstrate a significant structural lesion in the temporal lobe. To our knowledge, for the first time, these two cases suggest the existence of independent secondary epileptogenesis in humans.

Outcomes in newly diagnosed elderly glioblastoma patients after concomitant temozolomide administration and hypofractionated radiotherapy.

This study aimed to analyze the treatment and outcomes of older glioblastoma patients. Forty-four patients older than 70 years of age were referred to the Paul Strauss Center for chemotherapy and radiotherapy. The median age was 75.5 years old (range: 70-84), and the patients included 18 females and 26 males. The median Karnofsky index (KI) was 70%. The Charlson indices varied from 4 to 6. All of the patients underwent surgery. O6-methylguanine-DNA methyltransferase (MGMT) methylation status was determined in 25 patients. All of the patients received radiation therapy. Thirty-eight patients adhered to a hypofractionated radiation therapy schedule and six patients to a normofractionated schedule. Neoadjuvant, concomitant and adjuvant chemotherapy regimens were administered to 12, 35 and 20 patients, respectively. At the time of this analysis, 41 patients had died. The median time to relapse was 6.7 months. Twenty-nine patients relapsed, and 10 patients received chemotherapy upon relapse. The median overall survival (OS) was 7.2 months and the one- and two-year OS rates were 32% and 12%, respectively. In a multivariate analysis, only the Karnofsky index was a prognostic factor. Hypofractionated radiotherapy and chemotherapy with temozolomide are feasible and acceptably tolerated in older patients. However, relevant prognostic factors are needed to optimize treatment proposals.

Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesial temporal lobe epilepsy and unilateral hippocampal sclerosis.

Several studies have demonstrated the positive effect of resective epilepsy surgery in drug-resistant temporal lobe epilepsy (TLE). However, it is still a matter of debate whether selective amygdalohippocampectomy (SAH) or standard temporal lobectomy (STL) are the most effective approaches concerning seizure outcome, quality of life and memory. In each of the two centers participating in this study either SAH or STL was the neurosurgical standard procedure irrespective of contextual aspects. Thus, with this postoperative assessment of resected patients we sought to avoid any selection bias that usually impaired comparative trials of both surgical approaches. We finally identified and studied 95 adult patients who had undergone either SAH (n=46) or STL (n=49) between 1999 and 2009 and fulfilled the inclusion criteria, namely drug-resistant unilateral mesial TLE with hippocampal sclerosis without any further structural lesions. We assessed the postoperative seizure outcome according to the ILAE criteria and postoperative quality of life by means of standardized questionnaires. Finally, we compared postoperative neuropsychological performance in 60 completely seizure-free patients (n=27 after SAH, n=33 after STL) prior to, one year after surgery and at a long-term follow-up with a mean of seven years. 78.2% of SAH and 85.7% of STL were seizure-free at the last observation. Quality of life had improved in 95.6% of the SAH patients and 89.8% of the STL patients. These differences were not statistically significant. Left-sided TLE patients had a significantly worse verbal memory outcome irrespective of the surgical method. However, SAH patients had a significantly better outcome concerning visual encoding, verbal and visual short-term memory and visual working memory. In this study, seizure outcome and quality of life did not differ depending on the surgical approach. However, a more selective resection led to better neuropsychological performances.

Outcome Improvement in RPA I or II Patients With 1 or 2 Brain Metastases by Combined Surgery and Radiotherapy.

BACKGROUND: To evaluate the role of surgery and postoperative radiotherapy in the management of brain metastases (BM): a retrospective analysis for overall survival (OS), local and brain control (LC and BC) of a series of 329 patients with recursive partitioning analysis (RPA) I or II with 1 or 2 BM in a single institution. METHODS: Patients were treated either with combined surgical resection and whole brain radiation therapy (WBRT) in 104 cases (31.6%) or with WBRT alone in 225 cases (68.4%). Ninety-five patients (91.4%) who underwent surgery and WBRT and 147 (65.3%) who underwent WBRT alone benefited from a radiation boost to the metastatic site. RESULTS: The median OS was higher for patients RPA I compared to RPA II: 21.3 and 5.9 months (P < 0.0001), as well as for the surgical group compared to the radiation group: 20.2 vs 5.3 months (P < 0.0001), respectively. After the multivariate analysis, the improved OS was significantly associated with control of primary tumor (P = 0.0002) after surgical resection and with type of primary tumor (P = 0.002), absence of extracranial metastases (ECM) (P = 0.006), and high Karnofsky performance status (90 - 100 vs 70 - 80) (P = 0.003) after radiotherapy alone. The 12-, 24- and 36-months LC rates were 91.1%, 91.1% and 83.9%, respectively, after surgical resection and 81.2%, 63.1% and 57.3%, respectively, after radiotherapy alone (P = 0.005). In a univariate analysis, improved LC for the surgical group was also associated with the absence of ECM (P = 0.01) and for the radiation group, with a radiation boost (P = 0.01). The BC rates at 12, 24 and 36 months were 73.2%, 66.9% and 56%, respectively, in the surgical group and 75.7%, 49.6% and 42.4%, respectively, in the radiation group (P = 0.2). In our univariate analysis, improved BC after surgical resection was associated with control of primary tumor (P = 0.02). For patients in the radiation group, gender (P = 0.03) and a radiation boost (P = 0.0003) were significant prognostic factors in a univariate analysis. In our multivariate analysis, only the radiation boost was significant (P = 0.001). CONCLUSIONS: Surgical resection followed by WBRT leads to a better outcome compared to WBRT alone for RPA I or II patients with 1 or 2 BM.

Retrospective comparison of chemoradiotherapy followed by adjuvant chemotherapy, with or without prior gliadel implantation (carmustine) after initial surgery in patients with newly diagnosed high-grade gliomas.

PURPOSE: Retrospective study of patients treated for high-grade glioma, with or without biodegradable carmustine wafers and according to the Stupp protocol. METHODS AND MATERIALS: Between May 2007 and June 2008, 65 patients underwent surgery for high-grade glioma, 28 had implantation of Gliadel and 37 patients did not. Patients received radiotherapy with concomitant temozolomide followed by 5 consecutive days of temozolomide every month for 6 months. RESULTS: Overall median follow-up was 17.1 months; the median relapse-free survival (RFS) was 14 months with a RFS of 54% at 12 months, and 38% at 24 months. For patient with and without Gliadel, median and 1-year RFS were 12.9 months and 52% vs. 14 months and 42%, respectively (p = 0.89). According to pathology, Gliadel did not influence RFS of patients with Grade III or glioblastoma. However, for all patients, in multivariate analysis, non-methylated methylguanine methyltransferase (MGMT) was the only unfavorable prognostic factor of RFS (p = 0.017; HR 2.8; CI [1.2-7]). Median overall survival (OS) was 20.8 months; the OS rate at 12 months was 78.5%, and at 24 months 35.4%. For patients treated with and without Gliadel, median and 1-year OS were 20.6 months and 78.6% vs. 20.8 months and 78.4%, respectively. According to pathology, Gliadel did not influence OS of patients with Grade III or glioblastoma. For all patients, in multivariate analysis, unfavorable prognosticators for OS were non-methylated MGMT (p = 0.001; HR: 6.5; CI [2-20]) and irradiation dose <60 Gy (p = 0.02; HR: 6.3; CI [2-20]). With carmustine wafers, before irradiation, median gross tumor volume plus edema was 84 mL (27-229), whereas it was 68 mL (10-362) without carmustine (p = nonsignificant). Four cases of Grade 3 thrombopenia occurred, all in the carmustine wafer group. CONCLUSION: In patients with high-grade gliomas, adding Gliadel before performing a Stupp protocol did not improve survival.

Temporal lobe association fiber tractography as compared to histology and dissection.

OBJECTIVES: To compare the temporal lobe white matter fiber bundles obtained by diffusion tensor imaging-based tractography to that by histology and dissection, and to study the interindividual variability of the obtained tracts. MATERIALS AND METHODS: DTI (diffusion tensor imaging) acquisitions (30 directions) were obtained from nine healthy volunteers. Imaging post-processing was performed with FSL (FMRIB Software Library) software. Uncinate fasciculus, longitudinal inferior fasciculus and optic radiations were tracked after positioning of the region of interest (ROI) in predetermined anatomical landmarks. Histological data were obtained by cutting 15 µm coronal sections in one left brain hemisphere and staining with modified Heidenhain-Woelcke myelin stain. Dissection was performed on the left brain hemisphere prepared in accordance with the Klingler method. Tractography of each bundle was compared to histology and dissection data. To highlight the interindividual variability of the considered fiber tracts, all the images were affinely registered on an arbitrarily chosen reference image by considering the B0 images. Fiber tracts were then warped according to the corresponding estimated transformation and an average fiber tract image was then computed. RESULTS: Our results demonstrated a good concordance between tractography of the temporal lobe white matter bundles and dissection and histological data. The interindividual reproducibility of each tract seemed to be good, particularly in the middle part. The variability was more important at both ends, probably in relation to the dispersion of fiber bundles. CONCLUSION: Diffusion tensor imaging-based tractography of temporal lobe white matter tracts seemed to be in accordance with histological and dissection data. Taking into account some limitations, it could be of particular interest for the presurgical planning of temporal lobectomy.

Spontaneous spinal epidural hematomas in children: can we prevent a negative prognosis?--reflections on 2 cases.

Spontaneous spinal epidural hematomas in children are very rare and, until now, have not been described in infants. Spontaneous spinal epidural hematomas is characterized by a sudden onset of acute back pain followed by acute neurological deterioration within a few hours, but in younger children the initial symptoms are often nonspecific, leading to a delay in diagnosis and treatment. Although some cases have been reported, controversy persists as to its origin, diagnosis, and timing of treatment. We present 2 new cases of this rare condition: a 7-month-old girl who suffered from acute paraplegia and, unfortunately, did not recover after adequate spinal decompression. To our knowledge, this is the first reported case of spontaneous spinal epidural hematomas in an infant. We also report a similar observation in a 13.5-year-old boy who also suffered from acute paraplegia and had only a partial recovery after urgent decompression.

Do medulloblastoma tumors meet the Food and Drug Administration criteria for anti-erbB2 therapy with trastuzumab?

Several publications have recently focused on the erbB2 receptor in pediatric medulloblastomas (MBs) and its prognostic consequence. We determined erbB2 expression in 23 MBs at diagnosis. After DNA extraction, quantitative PCR targeting the erbB2 gene was performed and correlated with FISH analysis and immunohistochemistry. The samples were representative of the spectrum of the disease apart from the absence of large cell MBs. Using the tools validated for breast cancers by the FDA, we did not observe any expression or amplification of erbB2 and hence we speculate that MBs are not a good target for treatment with anti-erbB2 antibodies.