Non-fermentative Gram-negative rods bacteremia in children with cancer: a 14-year single-center experience.

PURPOSE: Data on non-fermentative Gram-negative rods (NFGNR) bacteremia in children with malignancies are limited. The aim of this study was to present clinical picture, antimicrobial susceptibility pattern, risk factors for resistance and outcome in NFGNR bacteremia in children with cancer. METHODS: All episodes of NFGNR bacteremia occurring during 2001-2014 in children with cancer in a tertiary-care hospital were retrospectively analyzed. Pseudomonas and Acinetobacter spp. resistant to three or more antibiotic classes and all Stenotrophomonas maltophilia (SM) were defined as multidrug-resistant bacteria (MDR). RESULTS: A total of 80 children (44 males, 0.8-18 years, median 5 years) developed 107 episodes (116 pathogens) of NFGNR bacteremia; Pseudomonas aeruginosa (PA) (51; 43.9%), Acinetobacter baumannii (AB) (21, 18.1%), SM (18, 15.5%); and others (27, 25.2%). The rate of NFGNR bacteremia in children with certain solid tumors (e.g. sarcoma, 12/134 (9.0%)) was comparable to that of hematological malignancies (52/429 (12.2%). Focal infection and septic shock occurred in 16 (14.9%) and four (3.7%) episodes, respectively. Thirty (25.8%) of 116 NFGNR were MDR. The most significant predictors of bacteremia with MDR PA or AB were severe neutropenia (<100 cells/mm3; OR 7.8, p = 0.002), hospital-acquired (OR 16.9, p < 0.0001) and breakthrough (OR 11.2, p < 0.0001) infection. Infection with MDR bacteria was associated with inappropriate empirical therapy. The 30-day mortality was 3/107 (2.8%), all in neutropenic patients with hematological malignancies. CONCLUSIONS: NFGNR bacteremia can present with nonspecific signs or symptoms. MDR NFGNRs are common and compromise treatment options, but mortality is relatively low. Knowledge of local epidemiology, pattern and risk factors for resistance is important to guide empirical therapy.

Taxanes-induced cutaneous eruption: another histopathologic mimicker of malignancy.

BACKGROUND: Paclitaxel and docetaxel are antineoplastic drugs that bind the microtubules, producing the arrest of mitoses, which may be seen histopathologically. These histopathologic changes may simulate an intraepidermal keratinocytic malignant neoplasm, and an accurate diagnosis may be only established by clinicopathological correlation. OBJECTIVES: We report six cases of cutaneous eruptions by taxanes in which a striking cytotoxic effect was evident histopathologically. METHODS: Cutaneous biopsies were obtained in each patient. RESULTS: Atypical starburst-like or ring-like mitoses and dyskeratosis on basal and suprabasal layers of the epidermis. Areas of squamous syringometaplasia were also seen in one case. DISCUSSION: These findings were interpreted as expression of mitotic arrest due to taxanes. Similar changes have been described in association with other chemotherapeutic drugs such as vincristine, podophyllin and its derivative etoposide; colchicine, busulfan and maytansine, but cases like ours due to taxanes are exceptional or under-reported. CONCLUSION: Dermatopathologists should be aware of these effects in order to interpret carefully cutaneous biopsy specimens of patients receiving taxanes.

[Merkel cell carcinoma]. / Merkel-Zell-Karzinom.

Merkel cell carcinoma (MCC, cutaneous neuroendocrine carcinoma) is a rare form of tumor of unclear histogenesis which predominantly occurs in elderly patients on areas exposed to the sun. A higher incidence and occurrence in younger people is predominantly found in immunosuppressed persons which is why a pathogenetic role is also attributed to immunosuppression in addition to ultraviolet (UV) radiation. Additionally, in 80% of cases clonally integrated polyomavirus (Merkel cell polyomavirus, MCPyV) could be detected. Clinically MCC represents an uncharacteristic tumor. Histopathologically, monomorphic dermal and/or subcutaneous nodes are found consisting of round or oval medium sized cells with a vesicular nucleus and sparse cytoplasm. The neoplastic cells of MCC express cytokeratin (CK) 20 with a dot-like perinuclear accentuation. In addition, pan-CK, neuroendocrine markers (e.g. chromogranin A and synaptophysin), neurofilament proteins, CD56, CD57, Bcl-2, TdT and PAX-5 are immunohistochemically positive. In most cases CM2B4, an antibody against MCPyV is also positive. Expression of p63 has been observed in some of the cases and in some studies was associated with a favorable prognosis. The markers thyroid transcription factor 1, mammalian achaete scute complex like 1, vimentin, S-100 and CK7 are not normally expressed by MCC. The prognosis is primarily dependent on tumor size and the lymph node status. The presence of intralymphatic tumor complexes is associated with a higher rate of local recurrence and lymph node metastasis. A larger number of intratumoral cytotoxic T-lymphocytes is accompanied by a favorable prognosis and the presence of > 50% of K-67+ neoplastic cells with an unfavorable prognosis. Further morphological, phenotypical and genetic factors have not yet been validated in larger cohorts with respect to the prognostic relevance.

Frequent loss of RAF kinase inhibitor protein expression in acute myeloid leukemia.

RAF kinase inhibitor protein (RKIP) is a negative regulator of the RAS-mitogen-activated protein kinase/extracellular signal-regulated kinase signaling cascade. We investigated its role in acute myeloid leukemia (AML), an aggressive malignancy arising from hematopoietic stem and progenitor cells (HSPCs). Western blot analysis revealed loss of RKIP expression in 19/103 (18%) primary AML samples and 4/17 (24%) AML cell lines but not in 10 CD34+ HSPC specimens. In in-vitro experiments with myeloid cell lines, RKIP overexpression inhibited cellular proliferation and colony formation in soft agar. Analysis of two cohorts with 103 and 285 AML patients, respectively, established a correlation of decreased RKIP expression with monocytic phenotypes. RKIP loss was associated with RAS mutations and in transformation assays, RKIP decreased the oncogenic potential of mutant RAS. Loss of RKIP further related to a significantly longer relapse-free survival and overall survival in uni- and multivariate analyses. Our data show that RKIP is frequently lost in AML and correlates with monocytic phenotypes and mutations in RAS. RKIP inhibits proliferation and transformation of myeloid cells and decreases transformation induced by mutant RAS. Finally, loss of RKIP seems to be a favorable prognostic parameter in patients with AML.

FDG-PET/MRI coregistration improves detection of cortical dysplasia in patients with epilepsy.

OBJECTIVE: Patients with cortical dysplasia (CD) are difficult to treat because the MRI abnormality may be undetectable. This study determined whether fluorodeoxyglucose (FDG)-PET/MRI coregistration enhanced the recognition of CD in epilepsy surgery patients. METHODS: Patients from 2004-2007 in whom FDG-PET/MRI coregistration was a component of the presurgical evaluation were compared with patients from 2000-2003 without this technique. For the 2004-2007 cohort, neuroimaging and clinical variables were compared between patients with mild Palmini type I and severe Palmini type II CD. RESULTS: Compared with the 2000-2003 cohort, from 2004-2007 more CD patients were detected, most had type I CD, and fewer cases required intracranial electrodes. From 2004-2007, 85% of type I CD cases had normal non-University of California, Los Angeles (UCLA) MRI scans. UCLA MRI identified CD in 78% of patients, and 37% of type I CD cases had normal UCLA scans. EEG and neuroimaging findings were concordant in 52% of type I CD patients, compared with 89% of type II CD patients. FDG-PET scans were positive in 71% of CD cases, and type I CD patients had less hypometabolism compared with type II CD patients. Postoperative seizure freedom occurred in 82% of patients, without differences between type I and type II CD cases. CONCLUSIONS: Incorporating fluorodeoxyglucose-PET/MRI coregistration into the multimodality presurgical evaluation enhanced the noninvasive identification and successful surgical treatment of patients with cortical dysplasia (CD), especially for the 33% of patients with nonconcordant findings and those with normal MRI scans from mild type I CD.

Electrical conductivities of the freshly excised cerebral cortex in epilepsy surgery patients; correlation with pathology, seizure duration, and diffusion tensor imaging.

The electrical conductivities (sigma) of freshly excised neocortex and subcortical white matter were studied in the frequency range of physiological relevance for EEG (5-1005 Hz) in 21 patients (ages 0.67 to 55 years) undergoing epilepsy neurosurgery. Surgical patients were classified as having cortical dysplasia (CD) or non-CD pathologies. Diffusion tensor imaging (DTI) for apparent diffusion coefficient (ADC) and fractional anisotropy (FA) was obtained in 9 patients. Results found that electrical conductivities in freshly excised neocortex vary significantly from patient to patient (sigma = 0.0660-0.156 S/m). Cerebral cortex from CD patients had increased conductivities compared with non-CD cases. In addition, longer seizure durations positively correlated with conductivities for CD tissue, while they negatively correlated for non-CD tissue. DTI ADC eigenvalues inversely correlated with electrical conductivity in CD and non-CD tissue. These results in a small initial cohort indicate that electrical conductivity of freshly excised neocortex from epilepsy surgery patients varies as a consequence of clinical variables, such as underlying pathology and seizure duration, and inversely correlates with DTI ADC values. Understanding how disease affects cortical electrical conductivity and ways to non-invasively measure it, perhaps through DTI, could enhance the ability to localize EEG dipoles and other relevant information in the treatment of epilepsy surgery patients.

Cortical lesions associated with transient neurological symptoms - not always a matter of cause and effect.

The occurrence of transient recurrent stereotypical neurological events mandates the exclusion of an underlying brain lesion. When imaging studies demonstrate the presence of a structural brain lesion, a cause and effect relationship between the two entities is assumed, and the decision for surgical intervention may then follow almost automatically. We describe five patients with transient neurological events suspected as being seizures that were referred for surgery because of an associated structural brain lesion. Video electroencephalographic recordings revealed that the events that brought these patients to neurosurgical attention were non-epileptic seizures. None of these patients underwent surgical intervention, and all were referred for behavioral therapy. Therefore, even in the presence of a confirmed brain lesion, the presenting paroxysmal events may be of a non-organic origin and should not necessarily be assumed to be caused by the concomitantly existing structural abnormality.

Ictal magnetic source imaging as a localizing tool in partial epilepsy.

OBJECTIVE: To determine the feasibility and usefulness of ictal magnetoencephalography (MEG) recordings in the presurgical evaluation of patients with epilepsy. METHODS: Twenty patients with frequent or predictable seizures were studied with the intent to capture seizures using a large array single-probe 37-channel or dual-probe 74-channel biomagnetometer. RESULTS: Successful ictal MEG recordings were made in 6 of 20 patients with neocortical epilepsy. In one other patient, a seizure was captured but movement artifact made MEG recordings impossible. As determined by invasive EEG recording and postsurgical outcome, ictal MEG provided localizing information that was superior to interictal MEG in three of the six patients. Localization of ictal onset by MEG was at least equivalent to invasive EEG in five of the six patients, and was superior in two patients as determined by postsurgical outcome. CONCLUSION: Larger studies are necessary to confirm that ictal MEG recordings in patients with frequent or easily provoked neocortical seizures can contribute localizing information equivalent or superior to invasive EEG recording.

Quality of life self-assessment as a function of lateralization of lesion in candidates for epilepsy surgery.

PURPOSE: This prospective study aimed to investigate the relationship(s) of the laterality of the epileptogenic lesion to personality factors, emotional processing, and the subjective experience of quality-of-life (QOL) self-assessment in candidates for epilepsy surgery. METHODS: Patients who were candidates for epilepsy surgery were studied. Eighteen of them (aged 19-61 years) had localization-related epilepsy in the right temporal lobe (RTLE), 18 (aged 21-50 years) had localization-related epilepsy in the left temporal lobe (LTLE), and 20 were demographically matched normal subjects. The Spielberger Trait/State Anxiety questionnaire and the QOLIE-31 questionnaire for self-assessment of quality of life were used. One-way analysis of variance, Pearson correlations, and linear regression analyses were performed on group and anxiety levels and QOLIE variables. RESULTS: LTLE patients systematically showed higher levels of anxiety and lower self-estimates of the quality of their lives when compared with RTLE patients. All anxiety measures were highly correlated with Total QOL in LTLE (p < 0.05) but not in RTLE patients; however, different parameters of QOL showed different relationships with measures of anxiety. Results of multiple regression analyses suggested that the level of anxiety was relatively stable and less affected by QOL factors in LTLE as compared with RTLE patients (p = 0.03). CONCLUSIONS: A high level of anxiety shown by LTLE patients may represent a personality trait and cause a response bias in overreporting of negative symptoms and a decreased self-assessment of QOL. It may also present a presurgical risk factor, particularly for patients with LTLE lesions. Appropriate patient counseling is advised.

Surgical treatment of hypothalamic hamartoma and refractory seizures: a case report and review of the literature.

Refractory gelastic seizures are often associated with hypothalamic hamartoma (HH). Presurgical evaluation in such children often points to a distinct cortical region as the source of the seizures. A case of a child with HH and refractory seizures is presented. Video-EEG monitoring revealed a well-defined epileptic focus in the left frontal region. In accordance with the current understanding of the nature of hamartoma-related seizures, the hamartoma was resected. Follow-up evaluations revealed a marked improvement in seizure frequency and global functioning.

[Presurgical neuropsychological assessment in epilepsy: the Wada test].

37 candidates for epilepsy surgery underwent the intracarotid amytal procedure (IAP; also known as the Wada test) to determine hemispheric speech dominance and memory capacity. 31 demonstrated left hemisphere speech dominance, 2 showed evidence for bilateral language and 4 demonstrated right hemispheric language dominance. Our study supports a correlational relationship between handedness, lesion laterality and age of onset of seizures, as reported in earlier studies. Left-handed patients with a left hemisphere lesion whose seizures began to an early age had a strong tendency for reversed language dominance. Asymmetry of at least 20% in performing the memory test was taken as the cutoff score for demonstrating laterality of lesions. The asymmetry score correctly predicted laterality of lesions in all 28 patients; 6 did not have asymmetry scores and 3 were examined for language only. None of the patients who successfully passed the Wada memory test had any significant postsurgical memory deficits; 1 had transient reduction in verbal memory and 4 who did not pass the test were not operated on for this reason. Our results demonstrate the importance of the Wada test in determining cerebral speech dominance, in predicting post-surgical amnesia, and support its usefulness in predicting laterality of seizure focus in candidates for temporal lobectomy.

The asleep-awake-asleep anesthetic technique for intraoperative language mapping.

OBJECTIVE: We evaluated a combined technique designed for procedures requiring intraoperative language mapping. We planned to induce general anesthesia with endotracheal intubation and hyperventilation and then to awaken and extubate the patient for speech testing. After the latter, endotracheal reintubation and general anesthesia were planned. METHODS: With the patient under intravenously induced sedation, we topically anesthetized the airway with lidocaine that was delivered through a spraying catheter. Fiberoptic endotracheal intubation was then performed on the awake patient, using a modified endotracheal tube. General anesthesia with intravenous propofol or sodium thiopental was induced, the patient's head was attached to a Mayfield holder, and the pin and operative sites were infiltrated with 0.5% bupivacaine with epinephrine. In anticipation of speech mapping, general anesthesia was discontinued and lidocaine was injected into the catheter that was spirally attached to the endotracheal tube. After speech mapping, the awake patients were endotracheally intubated, guided with the fiberoptic laryngoscope or tube changer, and general anesthesia was induced and maintained until termination of the surgery. RESULTS: We did not observe any complications, such as coughing or head movements, during the preparation for general anesthesia, awakening and endotracheal extubation for speech mapping, and post-testing reintubation or induction of general anesthesia. CONCLUSION: The combined technique that we describe abolished the potential discomfort of surgical stimulation on a sedated patient, reduced the duration of wakefulness, and provided a secure airway and the means to hyperventilate our patients before dural opening.

Auras and experiential responses arising in the temporal lobe.

Complex partial seizures and the auras that precede them are often manifestations of localized temporal lobe activity. Auras, unlike complex partial seizures, are reportable, since memory for them is retained. Similar experiences can be elicited by local electrical stimulation of mesial or lateral temporal cortex. Auras and "experiential phenomena" arising in the temporal lobe reflect dissociation of human experience into perceptual, mnemonic, and affective components, which in some cases can be specifically localized. Auras often persist following medial temporal lobe surgery, even when patients are rendered seizure-free. This suggests that these auras, like formed memories, are widely distributed and may eventually become consolidated in the neocortex.

Long-term follow-up after temporal lobe resection for lesions associated with chronic seizures.

A follow-up study was conducted on 60 patients who had standard en bloc anterior temporal lobe resection, including mesiotemporal structures, as treatment for temporal lobe lesions associated with chronic, medically intractable seizures. Lesions were identified as glial tumors, hamartomas, or vascular malformations. Long-term outcome was assessed in terms of seizure frequency and certain psychosocial sequelae. Seizure onset occurred at an average age of 15 years (median = 13.5 years), and patients experienced seizures for an average of 13 years prior to surgery. The mean time of follow-up was 8.4 years postsurgery (median = 6 years). The Kaplan-Meier curve at median follow-up showed a seizure-free rate of 80%. Late seizure recurrence was documented for three patients; two had been seizure-free for 10 years and one for 15 years after surgery, before re-onset of seizures in the absence of tumor recurrence. A prolonged history of seizures prior to surgery was associated with a poorer seizure outcome (p = 0.06), suggesting that secondary epileptogenesis at sites distant to the lesion may develop with years of uncontrolled seizures. There was a low tumor recurrence rate of 3.3% (two cases). The psychosocial outcome was generally good, with 67% working or engaged in educational studies, and improvement noted in 59% of cases for one or more of the psychosocial factors investigated. This study confirms that anterior temporal lobe resection for temporal lesions associated with chronic seizures is a successful treatment with a high seizure-free rate following surgery and good psychosocial outcome.

Long-term follow-up after temporal lobe resection for lesions associated with chronic seizures.

A follow-up study was conducted on 60 patients who had standard en bloc anterior temporal lobe resection, including mesio-temporal structures, as treatment for temporal lobe lesions associated with chronic, medically intractable seizures. Lesions were identified as glial tumors, hamartomas, or vascular malformations. Long-term outcome was assessed in terms of seizure frequency and certain psychosocial sequelae. Seizure onset occurred at an average age of 15 years (median = 13.5 years), and patients experienced seizures for an average of 13 years prior to surgery. The mean time of follow-up was 8.4 years post-surgery (median = 6 years). The Kaplan-Meier curve at median follow-up showed a seizure-free rate of 80%. Late seizure recurrence was documented for three patients; two had been seizure free for 10 years and one for 15 years after surgery before re-onset of seizures in the absence of tumor recurrence. A prolonged history of seizures prior to surgery was associated with a poorer seizure outcome (p = 0.06), suggesting that secondary epileptogenesis at sites distant to the lesion may develop with years of uncontrolled seizures. There was a low tumor recurrence rate of 3.3% (two cases). The psychosocial outcome was generally good, with 67% working or engaged in educational studies, and improvement noted in 59% of cases for one or more of the psychosocial factors investigated. This study confirms that anterior temporal lobe resection for temporal lesions associated with chronic seizures is a successful treatment with a high seizure-free rate following surgery and good psychosocial outcome.

Intracranial electrode monitoring for seizure localization: indications, methods and the prevention of complications.

Surgery is a successful method of treatment for certain epilepsies. Patient evaluation is directed towards seizure classification and localization. In most cases patients are able to progress from a noninvasive evaluation utilizing extracranial electrodes directly to resective surgery. In a few complex situations patient evaluation requires the placement of intracranial electrodes for accurate localization of the epileptogenic focus. The placement of intracranial electrodes is a surgical procedure which carries significant risk. Meticulous multidisciplinary care is required to achieve a safe and successful surgical outcome. Astute nursing care is pivotal to the success of intracranial monitoring and essential to the prevention of complications.

Subluxation injuries of maxillary primary anterior teeth: epidemiology and prognosis of 207 traumatized teeth.

This study investigated the epidemiology, sequelae, and prognosis of subluxation injuries to the maxillary primary anterior dentition. Data were collected from dental records at the Montreal Children's Hospital, Montreal, Canada, of patients sustaining trauma between 1982 and 1993. The study group consisted of 207 teeth in 134 patients, 81 males and 53 females. The age of the patients ranged from 0.8 years to 7.5 years, with a mean of 3.5 years. The highest incidence of trauma was in males between the ages of 3 and 4 years, and in females between 1 and 3 years. The highest incidence of trauma (66.2%) involved the primary central incisors. The most common cause of trauma (52%) was simple falls indoors. Occlusal or periapical radiographs were the radiographic view of choice unless an anterior nasal spine fracture was suspected, in which case a lateral projection was exposed. Approximately 64% of the study teeth had a mobility ranging from 0.6 to 1.5 mm. Treatment varied from no treatment (80% of teeth) to extraction. Post-traumatic evaluations were distributed into six common time intervals used by dentists for follow up. The results indicated that patient discomfort and occlusal interference were not common. Discoloration and pulpal calcification increased with time. Mobility decreased with time, with the majority of teeth returning to a normal physiologic range. External resorption may have been present, but was rare. Treatment or antibiotics were rarely needed at follow-up visits. Overall, these teeth responded positively, and there was a low morbidity associated with subluxation injuries.

Functional MR and PET imaging of rolandic and visual cortices for neurosurgical planning.

Magnetic resonance (MR) imaging has recently been used to demonstrate physiological activation of the human brain. This development is of considerable interest to the neurosurgeon planning procedures near brain regions involving specific functions. In the present study, rolandic and visual cortices were imaged with a conventional 1.5-tesla clinical MR imager using a spoiled gradient-recalled acquisition in the steady state sequence. Two patients, one with a right frontal astrocytoma and the other with a left parietal meningioma, underwent MR imaging of rolandic cortex while performing a repetitive finger apposition task. Two patients with complex partial seizures referable to the temporal and occipital regions underwent MR imaging of visual cortex while exposed to repetitive photic stimulation (8.3 Hz). Significant signal intensity changes up to 15% between the activation and rest conditions were observed near the surgical targets at the expected anatomical location of the rolandic and visual cortices. In two of these cases activation measured by MR was compared and found similar to the activation measured at the same plane by H2(15)O positron emission tomography (PET). These results suggest that functional MR and PET techniques can be used to obtain preoperative brain mapping in individual patients considered for neurosurgical procedures.

Human immunodeficiency virus 1 envelope proteins induce interleukin 1, tumor necrosis factor alpha, and nitric oxide in glial cultures derived from fetal, neonatal, and adult human brain.

Although microglia are the only cells found to be productively infected in the central nervous system of acquired immunodeficiency disease syndrome (AIDS) patients, there is extensive white and gray matter disease nonetheless. This neuropathogenesis is believed to be due to indirect mechanisms other than infection with human immunodeficiency virus 1 (HIV-1). Cytokines and toxic small molecules have been implicated in the clinical and histopathological findings in CNS AIDS. Previously, we have demonstrated in rodent glial cultures the presence of biologically active epitopes of gp120 and gp41 that are capable of inducing interleukin 1 and tumor necrosis factor alpha. In this study, we map the HIV-1 envelope epitopes that induce nitric oxide, inducible nitric oxide synthase, interleukin 1, and tumor necrosis factor alpha in human glial cultures. Epitopes in the carboxy terminus of gp120 and the amino terminus of gp41 induce these proinflammatory entities. In addition, we compare HIV-1 infection and pathology in glial cells derived from human brain taken at different states of maturation (fetal, neonatal, and adult brain) in an effort to address some of the clinical and histological differences seen in vivo. This study demonstrates that, in the absence of virus infection and even in the absence of distinct viral tropism, human glia respond like rodent glia to non-CD4-binding epitopes of gp120/gp41 with cytokine and nitric oxide production. Differences among fetal, neonatal, and adult glial cells' infectivity and cytokine production indicate that, in addition to functional differences of glia at different stages of development, cofactors in vitro and in vivo may also be critical in facilitating the biological responses of these cells to HIV-1.