Challenges in the treatment of breast cancer brain metastases: evidence, unresolved questions, and a practical algorithm.

Breast cancer is the leading cause of brain metastases in women. Large randomized clinical trials that have evaluated local therapies in patients with brain metastases include patients with brain metastases from a variety of cancer types. The incidence of brain metastases in the breast cancer population continues to grow, which is, aside from the rising breast cancer incidence, mainly attributable to improvements in systemic therapies leading to more durable control of extracranial metastatic disease and prolonged survival. The management of breast cancer brain metastases remains challenging, even more so with the continued advancement of local and highly effective systemic therapies. For most patients, a metastases-directed initial approach (i.e., radiation, surgery) represents the most appropriate initial therapy. Treatment should be based on multidisciplinary team discussions and a shared decision with the patients taking into account the risks and benefits of each therapeutic modality with the goal of prolonging survival while maintaining quality of life. In this narrative review, a multidisciplinary group of experts will address challenging questions in the context of current scientific literature and propose a therapeutic algorithm for breast cancer patients with brain metastases.

Disseminated pneumocephalus secondary to air compressor injury.

We report an unusual case of a young male patient who presented with severe pain and swelling of his left eyelid following an air compressor tip accident. He suffered extensive facial edema accompanied by deep tissue emphysema and an elevated intraocular pressure. On noncontrast CT scan, air was detected in the intraconal and extraconal orbital compartments, and intracranially within the subarachnoid spaces as well as in the suprasellar and perimesencephalic cisterns. There were no detectable fractures. We presume that by perforating the orbital septum, Tenon's capsule, and the optic nerve sheath, air had managed to penetrate the cranium through the optic nerve subarachnoid space and into the intracranial subarachnoid space.

Seasonal variation in spontaneous intracerebral hemorrhage in northern Israel.

The incidence of spontaneous intracerebral hemorrhage (sICH) and ischemic stroke vary across seasons. Most studies examining seasonal variation in sICH have been conducted in countries with significant climatic changes across seasons, whereas studies from the Mediterranean region, which has a relatively mild winter, are limited in number and have produced inconsistent results. Further studies from the region are called for, especially from countries where sICH seasonality has not yet been explored. A total of 974 patients with sICH between 1 January 2000 and 31 December 2014 were included in this study. The seasonal, monthly and weekday distribution of hospital admissions, in-hospital mortality, length of hospital stay and functional outcome at discharge were examined. We found that most hospital admissions due to sICH occurred in the winter (n = 286, 29%), whereas the fewest admissions occurred in the summer (n = 205, 21%; p = 0.0011). In terms of monthly distribution, most admissions were in January (n = 107, 11%), and the fewest admissions were in September (n = 60, 6%; p = 0.0004). There were no differences in the distribution of sICH between weekdays and weekends. Also, we found no significant weekday or seasonal variations in in-hospital mortality or functional outcome of sICH. Our results suggest that temporal patterns impact the natural course of sICH in northern Israel. The identification of factors, including biological ones, responsible for seasonal variation in regions with mild seasonal changes requires further research but could aid in the design of strategies for preventing sICH.

Risk factors associated with death or neurological deterioration among patients with Gram-negative postneurosurgical meningitis.

In a retrospective cohort of 115 patients with Gram-negative postneurosurgical meningitis, factors associated with 30-day mortality or neurological deterioration on multivariate analysis included days from admission to meningitis (OR 1.05 per day, 95% CI 1.02-1.09), decreased level of consciousness (OR 2.69, 95% CI 0.99-7.31), blood glucose level >180 mg/dL (OR 3.70, 95% CI 1.27-10.77), higher creatinine level (OR 4.07 per 1 mg/dL, 95% CI 1.50-11.08), and cerebrospinal fluid glucose <50 mg/dL (OR 5.02, 95% CI 1.71-14.77) at diagnosis. A predictive score triaged patients into three groups with low (4/44, 9.1%), intermediate (16/38, 42.1%) and high (22/33, 66.7%) unfavourable outcome rates. Validation on a different group of 36 patients with Gram-negative postneurosurgical meningitis was acceptable.

Intrathecal or intraventricular therapy for post-neurosurgical Gram-negative meningitis: matched cohort study.

Gram-negative post-operative meningitis due to carbapenem-resistant bacteria (CR-GNPOM) is a dire complication of neurosurgical procedures. We performed a nested propensity-matched historical cohort study aimed at examining the possible benefit of intrathecal or intraventricular (IT/IV) antibiotic treatment for CR-GNPOM. We included consecutive adults with GNPOM in two centres between 2005 and 2014. Patients receiving combined systemic and IT/IV treatment were matched to patients receiving systemic treatment only. Matching was done based on the propensity of the patients to receive IT/IV treatment. We compared patient groups with 30-day mortality defined as the primary outcome. The cohort included 95 patients with GNPOM. Of them, 37 received IT/IV therapy in addition to systemic treatment (22 with colistin and 15 with amikacin), mostly as initial therapy, through indwelling cerebrospinal fluid drains. Variables associated with IT/IV therapy in the propensity score included no previous neurosurgery, time from admission to meningitis, presence of a urinary catheter and GNPOM caused by carbapenem-resistant Gram-negative bacteria. Following propensity matching, 23 patients given IT/IV therapy and 27 controls were analysed. Mortality was significantly lower with IT/IV therapy: 2/23 (8.7%) versus 9/27 (33.3%), propensity-adjusted OR 0.19, 95% CI 0.04-0.99. Death or neurological deterioration at 30 days, 14-day and in-hospital mortality were lower with IT/IV therapy (OR <0.4 for all) without statistically significant differences. Among patients discharged alive, those receiving IT/IV therapy did not experience more neurological deterioration. Serious adverse events with IT/IV therapy were not documented. Our results support the early use of IT antibiotic treatment for CR-GNPOM when a delivery method is available.

Brainstem hypoperfusion in severe symptomatic vasospasm following aneurysmal subarachnoid hemorrhage: role of basilar artery vasospasm.

BACKGROUND: The hemodynamic effects of vertebrobasilar vasospasm are ill defined. The purpose of this study was to determine the effects of basilar artery (BA) vasospasm on brainstem (BS) perfusion. METHODS: Forty-five patients with delayed ischemic neurological deficits (DIND) following aneurysmal subarachnoid hemorrhage (SAH) underwent cerebral angiography prior to decision-making concerning endovascular treatment. BA diameter was compared with baseline angiogram. Regional brainstem (BS) cerebral blood flow (CBF) was qualitatively estimated by (99m)Tc ethyl cysteinate dimer single photon emission computed tomography (ECD-SPECT). FINDINGS: Delayed BS hypoperfusion was found in 22 (48.9%) of 45 patients and BA narrowing of more than 20% was found in 23 (51.1%). Seventeen of 23 (73.9%) patients with BA narrowing of more than 20% experienced BS hypoperfusion compared to 6 of 22 (27.3%) patients with minimal or no narrowing (p = 0.0072). Patients with severe and moderate BS hypoperfusion had higher degree of BA narrowing compared to patients with normal BS perfusion and mild BS hypoperfusion (p < 0.001). The three-month outcome of patients n-22) with BS hypoperfusion was significantly worse compared to patients (n-23) with unimpaired (p = 0.0377, odd ratio for poor outcome 4, 1.15-13.9 95% confidence interval). INTERPRETATION: These findings suggest that the incidence of BA vasospasm in patients with severe symptomatic vasospasm is high and patients with significant BA vasospasm are at higher risk to experience BS ischemia. Further studies should be done to evaluate the effects of endovascular therapy on BS perfusion and the impact of BS ischemia on morbidity and mortality of patients with severe symptomatic vasospasm.

Alteration in brain natriuretic peptide (BNP) plasma concentration following severe traumatic brain injury.

BACKGROUND: Brain natriuretic peptide (BNP) is a potent natriuretic and vasodilator factor which, by its systemic effects, can decrease cerebral blood flow (CBF). In aneurysmal subarchnoid hemorrhage (aSAH), BNP plasma concentrations were found to be associated with hyponatremia and were progressively elevated in patients who eventually developed delayed ischemic deficit secondary to vasospasm. The purpose of the present study was to evaluate trends in BNP plasma concentrations during the acute phase following severe (traumatic brain injury) TBI. METHODS: BNP plasma concentration was evaluated in 30 patients with severe isolated head injury (GCS<8 on admission) in four time periods after the injury (period 1: days 1-2; period 2: days 4-5; period 3: days 7-8; period 4: days 10-11). All patients were monitored for ICP during the first week after the injury. FINDINGS: The initial BNP plasma concentrations (42+/-36.9 pg/ml) were 7.3 fold (p<0.01) higher in TBI patients as compared to the control group (5.78+/-1.90 pg/ml). BNP plasma concentrations were progressively elevated through days 7-8 after the injury in patients with diffused SAH as compared to patients with mild or no SAH (p<0.001) and in patients with elevated ICP as compared to patients without elevated ICP (p<0.001). Furthermore, trends in BNP plasma concentrations were significantly and positively associated with poor outcome. INTERPRETATION: BNP plasma concentrations are elevated shortly after head injury and are continuously elevated during the acute phase in patients with more extensive SAH and in those with elevated ICP, and correlate with poor outcomes. Further studies should be undertaken to evaluate the role of BNP in TBI pathophysiology.

Role of dural fenestrations in acute subdural hematoma.

OBJECT: Patients with acute subdural hematomas (ASDHs) have higher mortality and lower functional recovery rates compared with those of other head-injured patients. Early surgical decompression and active intensive care treatment represent, so far, the best way to assist these patients. Paradoxically, one of the factors contributing to poor outcomes in cases of ASDHs could be rapid surgical decompression, owing to the severe extrusion of the brain through the craniotomy defect in response to acute brain swelling. To avoid the deleterious consequences of abrupt decompression of the subdural space with disruption of brain tissue, the authors have adopted a new surgical technique for evacuation of ASDHs. This procedure consists of creating multiple fenestrations of the dura (MFD) in a meshlike fashion and removing clots through the small dural openings that are left open, avoiding the creation of a wide dural opening and the disruption of and additional damage to brain tissue. METHODS: Thirty-one patients (26 male and five female patients with a mean age of 32.5 years) harboring ASDHs were treated using this method. On admission there were 16 patients (51.5%) with Glasgow Coma Scale (GCS) scores of 3 to 5, 11 patients (35.5%) with GCS scores of 6 to 8, and four patients (12.9%) with GCS scores of 9 to 12. Postoperative computerized tomography scans of the brain revealed evacuation of more than 80% of the hematoma in 29 of 31 patients. The overall mortality rate in this group was 51.6%. CONCLUSIONS: This preliminary report of a new surgical approach for patients who have sustained ASDHs should be considered to avoid abrupt disruption of the brain and to allow the gradual and gentle release of subdural clots. This is especially important in cases in which there are severe midline shifts and a tight brain. Further clinical studies should be conducted in a more selected series to estimate the impact of this new procedure on morbidity and mortality rates.

Brain natriuretic peptide and cerebral vasospasm in subarachnoid hemorrhage. Clinical and TCD correlations.

BACKGROUND AND PURPOSE: Hyponatremia has been shown in association with cerebral vasospasm (CVS) following aneurysmal subarachnoid hemorrhage (SAH). In the past few years there has been increasing evidence that brain natriuretic peptide (BNP) is responsible for natriuresis after SAH. The purpose of the present study was to investigate the relationship between BNP plasma concentrations and CVS after aneurysmal SAH. METHODS: BNP plasma concentrations were assessed at 4 different time periods (1 to 3 days, 4 to 6 days, 7 to 9 days, and 10 to 12 days) in 19 patients with spontaneous SAH. BNP plasma levels were investigated with respect to neurological condition, SAH severity on CT, and flow velocities measured by means of transcranial Doppler. RESULTS: Thirteen patients had Doppler evidence of CVS; 7 of these had nonsymptomatic CVS. In 6 patients, CVS was severe and symptomatic, with delayed ischemic lesion on CT in 5 of these. CVS was severe and symptomatic in 6 patients, and delayed ischemic lesions were revealed on CT in 5 of these. BNP levels were found to be significantly elevated in SAH patients compared with control subjects (P=0.024). However, in patients without CVS or with nonsymptomatic CVS, BNP concentrations decreased throughout the 4 time periods, whereas a 6-fold increase was observed in patients with severe symptomatic CVS between the first and the third periods (P=0.0096). A similar trend in BNP plasma levels was found in patients with severe SAH compared with those with nonvisible or moderate SAH (P=0.015). CONCLUSIONS: In conclusion, our results show that BNP plasma levels are elevated shortly after SAH, although they increase markedly during the first week in patients with symptomatic CVS. The present findings suggest that secretion of BNP secretion after spontaneous SAH may exacerbate blood flow reduction due to arterial vasospasm.

Penetrating head injuries caused by a new weapon, the side dome.

The "side dome" is a mix of high and low explosives with a multitude of small metal balls molded within a specially designed half-sphere that directs the explosion wave and the projectiles in one direction to augment the harm. This weapon, originally designed by guerrilla and terrorist groups, is now used by regular armies. This report presents one craniocervical and eight cranial injuries caused by this new weapon and discusses the cases' various clinical features, the paucity of intracerebral cavitation damage along the missile track, the need for only minimally aggressive surgery, and the relatively favorable outcome. In all cases, the helmet offered good protection and the entry of the projectiles was just below its rim in an upward direction.

[Radiation-induced meningioma: the changing pattern of the disease].

In this country radiation-induced meningiomas were usually associated with low-dose irradiation of the scalp of immigrants from North Africa, given as part of the treatment of tinea capitis. An Ashkenazi patient developed meningiomas 15 years after high-dose irradiation for a benign lesion in the parasellar region. The accumulating literature about high-dose radiation-induced meningiomas is reviewed and attention is drawn to the ever increasing number of meningiomas observed in immigrants from the former Soviet Union.

[An achondroplastic dwarf with paraplegia].

A 30-year-old female achondroplastic dwarf developed a progressive gait disturbance erroneously attributed to her hydrocephalus and deformities of both legs. Her condition deteriorated into flaccid paraplegia with anal and urinary incontinence. CT revealed extreme spinal stenosis typical in achondroplasia (shallow vertebral body, short pedicles, and hypertrophy of intervertebral joints) together with disc protrusions. Wide laminectomy of the lumbar vertebrae resulted in complete amelioration of all the neurological deficits. Progressive paraplegia is a rare complication of achondroplasia; its early recognition and surgical treatment is very rewarding.

[Idiopathic hypereosinophilic syndrome].

The idiopathic hypereosinophilic syndrome is a heterogeneous group of disorders characterized by persistent eosinophilia of undetected cause, and multiple organ system involvement. The systems affected include the central and peripheral nervous, cardiovascular, respiratory and gastrointestinal systems and the kidneys, skin, muscles and joints. Treatment is mainly by immunosuppressive drugs to prevent organ system complications. Prognosis is variable, depending mainly on heart involvement.