Occult tumors presenting with negative imaging: analysis of the literature.

Some patients presenting with neurological symptoms and normal findings on imaging studies may harbor occult brain tumors that are undetectable on initial imaging. The purpose of this study was to analyze the cases of occult brain tumors reported in the literature and to determine their modes of presentation and time to diagnosis on imaging studies.


A review of the literature was performed using PubMed. The authors found 15 articles reporting on a total of 60 patients with occult tumors (including the authors’ illustrative case).


Seizures were the mode of initial presentation in a majority (61.7%) of patients. The initial imaging was CT scanning in 55% and MRI in 45%. The mean time to diagnosis for occult brain tumors was 10.3 months (median 4 months). The time to diagnosis (mean 7.5 months, median 3.2 months) was shorter (p = 0.046) among patients with seizures. Glioblastoma multiforme (GBM) was found more frequently among patients with seizures (67.6% vs 34.8%, p = 0.013). The average time to diagnosis of GBM was shorter than the time to diagnosis of other tumors; the median time to diagnosis was 3.2 months for GBM and 6 months for other tumors (p = 0.04). There was no predilection for side or location of occult tumors. In adult patients, seizures may be predictive of left-sided tumors (p = 0.04).


Based on the results of this study, the authors found that in patients with occult brain tumors, the time to diagnosis is shorter among patients with seizures and also among those with GBM.

Source: Journal of Neurosurgery.



Dual regeneration of muscle and nerve by intravenous administration of human amniotic fluid–derived mesenchymal stem cells regulated by stromal cell–derived factor-1α in a sciatic nerve injury model .


Human amniotic fluid–derived mesenchymal stem cells (AFMSCs) have been shown to promote peripheral nerve regeneration. The expression of stromal cell–derived factor-1α (SDF-1α) in the injured nerve exerts a trophic effect by recruiting progenitor cells that promote nerve regeneration. In this study, the authors investigated the feasibility of intravenous administration of AFMSCs according to SDF-1α expression time profiles to facilitate neural regeneration in a sciatic nerve crush injury model.


Peripheral nerve injury was induced in 63 Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into 1 of 3 groups: Group I, crush injury as the control; Group II, crush injury and intravenous administration of AFMSCs (5 × 106 cells for 3 days) immediately after injury (early administration); and Group III, crush injury and intravenous administration of AFMSCs (5 × 106 cells for 3 days) 7 days after injury (late administration). Evaluation of neurobehavior, electrophysiological study, and assessment of regeneration markers were conducted every week after injury. The expression of SDF-1α and neurotrophic factors and the distribution of AFMSCs in various time profiles were also assessed.


Stromal cell–derived factor-1α increased the migration and wound healing of AFMSCs in vitro, and the migration ability was dose dependent. Crush injury induced the expression of SDF-1α at a peak of 10–14 days either in nerve or muscle, and this increased expression paralleled the expression of its receptor, chemokine receptor type-4 (CXCR-4). Most AFMSCs were distributed to the lung during early or late administration. Significant deposition of AFMSCs in nerve and muscle only occurred in the late administration group. Significantly enhanced neurobehavior, electrophysiological function, nerve myelination, and expression of neurotrophic factors and acetylcholine receptor were demonstrated in the late administration group.


Amniotic fluid–derived mesenchymal stem cells can be recruited by expression of SDF-1α in muscle and nerve after nerve crush injury. The increased deposition of AFMSCs paralleled the expression profiles of SDF-1α and its receptor CXCR-4 in either muscle or nerve. Administration of AFMSCs led to improvements in neurobehavior and expression of regeneration markers. Intravenous administration of AFMSCs may be a promising alternative treatment strategy in peripheral nerve disorder.

Source: Journal of Neurosurgery.



Researchers find antibiotic-resistant bacteria deep in one of the largest, unspoiled underground caves.

McMaster University and University of Akron researchers are leading the way in understanding the origins of antibiotic resistance, a global challenge that is creating a serious threat to the treatment of infectious diseases.

Gerry Wright, scientific director of the Michael G. DeGroote Institute for Infectious Disease Research (IIDR) at McMaster University, and Hazel Barton, associate professor of biology at the University of Akron, discovered a remarkable prevalence of antibiotic resistance bacteria isolated from Lechuguilla Cave in New Mexico, one of the deepest and largest caves in the world and a place isolated from human contact for more than four million years.

The research was published today in the Journal PLoS ONE.

“Our study shows that antibiotic resistance is hard-wired into bacteria, it could be billions of years old, but we have only been trying to understand it for the last 70 years,” says Wright. “This has important clinical implications. It suggests that there are far more antibiotics in the environment that could be found and used to treat currently untreatable infections.”

Amid the rare beauty of the Lechuguilla Cave, in Carlsbad Cavern National Park, researchers collected strains of bacteria from its deep and isolated recesses. They then examined these bacteria for antibiotic resistance. They found that while none of the bacteria are capable of causing human disease nor have they ever been exposed to human sources of antibiotics, almost all were resistant to at least one antibiotic, and some were resistant to as many as 14 different antibiotics. In all, resistance was found to virtually every antibiotic that doctors currently use to treat patients.

For instance, the researchers were able to identify a type of resistance that has yet to emerge in the clinic in a group of bacteria distantly related to the bacterium that causes anthrax.

Says Barton: “We can say to doctors, ‘while this isn’t a problem right now, it could be in the future so you need be aware of this pre-existing resistance and be prepared if it emerges in the clinic. Or you are going to have a problem’.”

The development of antibiotic resistant bacteria is becoming an increasing health concern. With the emergence of bacteria, such as multi-drug resistant Staphylococcus and the global spread of resistance to all clinically used drugs, where and how these organisms acquire resistance is an important question, says Wright.

“Most practitioners believe that bacteria acquire antibiotic resistance in the clinic,” he says. “As doctors prescribe antibiotics, they select for members of the community that are resistant to these drugs. Over time, these organisms spread and eventually the bacteria that commonly cause these infections are all resistant. In extreme cases these organisms are resistant to seven or more drugs and are untreatable using traditional treatment, and ¬ doctors must resort to surgery to remove infected tissue. The actual source of much of this resistance are harmless bacteria that live in the environment.”

Because antibiotics are heavily prescribed and used in agriculture, it is difficult to find an environment where antibiotics do not exert some kind of influence, adds Barton, noting this is why Lechuguilla Cave was the perfect environment to look at the pre-existing reservoir of antibiotic resistance in nature. Discovered in 1986, access to the cave has been limited to a few expert cavers and researchers each year. It is also surrounded by an impermeable layer of rock, meaning infiltration of water into the cave can take up to 10,000 years to reach its deepest recesses, an age well beyond the discovery of antibiotics. The researchers sampled bacteria from so far deep into the cave that Barton and some other researchers involved in the study camped in the cave during the collection process.

Their findings support recent studies at McMaster that suggest antibiotic resistance has a long evolutionary past.

Source:  McMaster University .

Long-term natural history of neurofibromatosis Type 2–associated intracranial tumors.

Neurofibromatosis Type 2 (NF2) is a heritable tumor predisposition syndrome that leads to the development of multiple intracranial tumors, including meningiomas and schwannomas. Because the natural history of these tumors has not been determined, their optimal management has not been established. To define the natural history of NF2-associated intracranial tumors and to optimize management strategies, the authors evaluated long-term clinical and radiographic data in patients with NF2.


Consecutive NF2 patients with a minimum of 4 years of serial clinical and MRI follow-up were analyzed.


Seventeen patients, 9 males and 8 females, were included in this analysis (mean follow-up 9.5 ± 4.8 years, range 4.0–20.7 years). The mean age at initial evaluation was 33.2 ± 15.5 years (range 12.3–57.6 years). Patients harbored 182 intracranial neoplasms, 164 of which were assessable for growth rate analysis (18 vestibular schwannomas [VSs], 11 nonvestibular cranial nerve [CN] schwannomas, and 135 meningiomas) and 152 of which were assessable for growth pattern analysis (15 VSs, 9 nonvestibular CN schwannomas, and 128 meningiomas). New tumors developed in patients over the course of the imaging follow-up: 66 meningiomas, 2 VSs, and 2 nonvestibular CN schwannomas. Overall, 45 tumors (29.6%) exhibited linear growth, 17 tumors (11.2%) exhibited exponential growth, and 90 tumors (59.2%) displayed a saltatory growth pattern characterized by alternating periods of growth and quiescence (mean quiescent period 2.3 ± 2.1 years, range 0.4–11.7 years). Further, the saltatory pattern was the most frequently identified growth pattern for each tumor type: meningiomas 60.9%, VSs 46.7%, and nonvestibular schwannoma 55.6%. A younger age at the onset of NF2-related symptoms (p = 0.01) and female sex (p = 0.05) were associated with an increased growth rate in meningiomas. The identification of saltatory growth in meningiomas increased with the duration of follow-up (p = 0.01).


Neurofibromatosis Type 2–associated intracranial tumors most frequently demonstrated a saltatory growth pattern. Because new tumors can develop in NF2 patients over their lifetime and because radiographic progression and symptom formation are unpredictable, resection may be best reserved for symptom-producing tumors. Moreover, establishing the efficacy of nonsurgical therapeutic interventions must be based on long-term follow-up (several years).

Source: Journal of Neurosurgery.


Albumin for Spontaneous Bacterial Peritonitis: For High-Risk Patients Only.

More evidence that patients with cirrhosis who have intact renal function and low serum bilirubin levels probably do not need albumin during SBP

In a previous randomized study of patients with cirrhosis, intravenous albumin administered with antibiotic therapy reduced the incidence of renal failure and death from spontaneous bacterial peritonitis (SBP) (N Engl J Med 1999; 341:403). Subsequent studies have suggested that patients with cirrhosis who have intact renal function and low serum bilirubin levels may not need albumin during SBP. However, these studies were performed in a selected patient population that might not reflect general practice.

Now, investigators have retrospectively examined outcomes in a nonselected cohort of patients with cirrhosis who received treatment for SBP at a single center in Spain that is representative of a community practice. Patients were considered to have low risk for mortality if urea level was <11 mmol/L and bilirubin was <68 µmol/L during the SBP episode and high risk for mortality if urea level was 11 mmol/L and bilirubin was 68 µmol/L. All patients received antibiotics (mostly cefotaxime or ceftriaxone for 7 days). Some high-risk patients also received albumin infusion (1.5 g/kg of body weight on day 1 and 1 g/kg on day 3). The main study endpoints were in-hospital mortality, probability of survival at 3 months, and development of renal failure (serum creatinine level >133 µmol/L).

During 7 years, 216 episodes of SBP occurred in 167 patients; 30% of episodes occurred in low-risk patients, and 70% occurred in high-risk patients. Compared with episodes in high-risk patients, episodes in low-risk patients resulted in lower rates of renal failure before SBP resolution (4.7% vs. 25.6%; P=0.001) and in-hospital mortality (3.1% vs. 38.2%; P<0.001) and higher 3-month survival (93% vs. 53%; P<0001). High-risk patients who received both albumin and antibiotics versus antibiotics alone had lower in-hospital mortality (28.8% vs. 46.8%; P=0.02) and higher 3-month survival (62% vs. 45%; P=0.01).

Comment: These results confirm earlier findings that not all patients with cirrhosis who experience an acute episode of spontaneous bacterial peritonitis require albumin infusion. Albumin infusions can be limited to patients with high bilirubin and urea levels, which reflect liver and renal function.

Source: Journal Watch Gastroenterology

First Complex Febrile Seizure Portends Low Risk for Intracranial Pathology.

Fewer than 1% of children with first complex febrile seizure and a normal neurological examination have clinically important intracranial pathology.

Investigators retrospectively assessed risk for clinically important intracranial pathology detected on neuroimaging in previously healthy children ages 6 to 60 months with first complex febrile seizures. The study involved a cohort of 526 patients (median age, 17 months) who presented to a tertiary pediatric emergency department (ED) between 1995 and 2008 within 12 hours of the seizure. Patients with trauma, ventriculoperitoneal shunts, or prior seizure disorders were excluded. Seizures were defined as complex if they lasted >15 minutes, presented as a series, recurred within 24 hours, or if clinical findings suggested focality. Imaging findings were considered clinically important if emergent neurosurgical or medical intervention were required.

Overall, 268 patients underwent head computed tomography (CT), 6 underwent magnetic resonance imaging (MRI), and 8 underwent both. Four patients (1.5%) had clinically important intracranial findings: two intracranial bleeds identified on CT, one right-sided low-density cerebellar lesion identified on CT, and one disseminated encephalomyelitis found only on MRI. Only one patient with clinically important findings (a 4-year-old boy with frontoparietal hematoma that did not require surgery or intracranial pressure monitoring) was otherwise well-appearing and had a normal neurologic exam. Among patients who did not undergo neuroimaging, none returned to the study site within the next 7 days; however, other EDs were not queried. When the analysis included patients who were not imaged but were presumed to be well because they did not return to the ED within 7 days, the risk of clinically important intracranial findings was 0.8%.

Comment: As is the case for simple febrile seizures, most children with normal mental status and normal neurological examination do not require emergent imaging after a first complex febrile seizure. Those with an otherwise reassuring evaluation can be discharged with outpatient neuroimaging to assess for nonemergent structural abnormalities.

Published in Journal Watch Emergency Medicine.