Dichlorophene activates aryl hydrocarbon receptor (AhR) and indoleamine 2, 3-dioxygenase 1 (IDO1) to mediate splenotoxicity in rat.

Dichlorophene (DCP) is a halogenated phenolic compound, widely used as fungicide, bactericide and antiprotozoan and also exhibit therapeutic application in several pathological conditions. Taking account of broad use of DCP, its possible effect on spleen (an important immune organ) was investigated in this study. Male albino rats were treated with graded doses of DCP (10%, 20% and 30% of LD50) and spleen and blood were obtained at 24, 48 and 72 hours post treatment. Oxidative stress parameters, proinflammatory cytokines and protein expression of aryl hydrocarbon receptor (AhR), indoleamine-2, 3-Dioxygenase 1 (IDO1) and nuclear factor erythroid 2-related factor 2 (Nrf2) were measured along with histopathological evaluation of spleen. In the present study, DCP perturbs redox status of splenocytes of rats as evidenced by excess ROS generation, lipid peroxidation and nitric oxide production simultaneously with reduction of antioxidant level [glutathione (GSH)] and inhibition of antioxidative enzymes [superoxide dismutase (SOD) and catalase (CAT)]. Two important proinflammatory cytokines, IL-6 and TNF-α were found to be elevated upon DCP treatment. Moreover, DCP also caused activation of AhR and IDO1 with simultaneous down regulation of Nrf2. All these effects of DCP were found to be dose and duration dependent. DCP also affects the spleen micro-architecture in the present study and these alterations were more prominent in high dose group at 72 hours post treatment. Taken together, all these results suggested that DCP induces oxidative stress and also increases proinflammatory cytokine levels to mount its toxic effect on spleen.

Gamma knife radiosurgery for brain metastasis of nonsmall cell lung cancer: is there a difference in outcome between morning and afternoon treatment?

BACKGROUND: Circadian cell-cycle progression causes fluctuating radiosensitivity in many tissues, which could affect clinical outcomes. The purpose of this study was to determine whether outcomes of single-session gamma knife radiosurgery (GKRS) for metastatic nonsmall cell lung cancer (NSCLC) differ based on treatment time. METHODS: Fifty-eight patients received GKRS between 10:00 am and 12:30 pm and 39 patients received GKRS between 12:30 pm and 3:00 pm. The mean peripheral dose was 18.6 Gy. The mean tumor size was 7.3 cm³. Magnetic resonance imaging was used to score local control at 3 months. Cause of death (COD) was categorized as central nervous system (CNS)-related or systemic. RESULTS: Demographic and disease characteristics of the 2 groups were similar. Local control at 3 months was achieved in 97% (35/36) of patients who underwent GKRS early in the day versus 67% (8/12) of patients who underwent GKRS later in the day (chi-square, P = .014). Early GKRS was associated with better survival (median 9.5 months) than late GKRS (median 5 months) (Kaplan-Meier log-rank test, P = .025). Factors contributing to better survival in a Cox regression model included early treatment time (P = .004) and recursive partition analysis class (P < .001). Cause of death in the early treatment group was CNS-related in 6% (3/47) of patients versus 24% (8/34) of patients in the late treatment group (chi-square test, P = .026). CONCLUSIONS: GKRS for metastatic NSCLC had better local control, better survival, and a lower rate of CNS-related cause of death when given earlier in the day versus later in the day. These retrospective data should encourage future study in brain radiosurgery and non-CNS stereotactic body radiotherapy series.

Trigeminal neuralgia in young adults.

OBJECT: Trigeminal neuralgia (TN) is a form of facial pain that can be debilitating if left untreated. It typically affects elderly adults and is thought to be related to neurovascular compression. It is uncommon in people younger than 30 years of age, with only 1% of cases reportedly occurring in those younger than 20 years of age. The most common cause of compression in young adults is thought to be venous nerve compression either alone or in association with arterial nerve compression. The objective of this study was to review data in cases of TN in which patients were 25 years of age or younger and to identify TN disease characteristics, demographics, clinical features, operative findings, and outcome. METHODS: The authors retrospectively reviewed the clinical records, surgical treatment, and long-term outcome in patients 25 years of age or younger with TN who underwent surgery performed by the senior author (K.J.B.) at Oregon Health & Science University between 1995 and 2008. RESULTS: Seven patients (2 males and 5 females) met the inclusion criteria. The average age at symptom onset was 19.6 ± 3.4 years (± SD) and the average age at surgery was 22.9 ± 1.7 years. Six patients had right-sided symptoms and 1 had left-sided symptoms. Pain distribution was the V2 in 3 cases, V2-3 in 3 cases, and V3 in 1 case, with no cases of V1 affliction. A total of 11 procedures were performed in 7 patients, and 4 patients underwent a second procedure. Surgery and imaging revealed venous compression in all cases. The average follow-up period was 35.5 ± 39.9 months (median 12 months). Three patients reported a good outcome (no pain with or without medications) and 4 reported a poor outcome (either no pain relief or mild pain relief after surgery). CONCLUSIONS: Trigeminal neuralgia is uncommon in young adults. Patients tend to present with symptoms similar to those in adults: long periods of pain and venous compression, but outcome unfortunately is not as good as that reported in the older population.

Surgical outcome and improvement in quality of life after microvascular decompression for hemifacial spasms: a case series assessment using a validated disease-specific scale.

BACKGROUND: Hemifacial spasm (HFS) is a movement disorder characterized by intermittent, involuntary clonic or tonic-clonic contractions of muscles innervated by the ipsilateral facial nerve. Recent studies have documented change in quality of life after HFS management with botulinum toxin injection. However, we failed to locate any study that documented change in quality of life after surgical management with retrosigmoid microvascular decompression (MVD). METHODS: Our study objectives were 3-fold. Firstly, to use a disease-specific, validated quality of life assessment scale to document any change in quality of life after MVD for HFS. Secondly, to determine the time period in which the majority of patients undergoing MVD could be expected to benefit from surgery. Finally, to determine factors affecting the postoperative quality of life following MVD. A retrospective analysis of HFS patients treated with MVD at a single institution by a single surgeon (K.J.B.) between January 2000 and December 2007 was undertaken. A modification of a previously developed validated disease-specific quality of life assessment scale that included the addition of a parameter for difficulty in sleep was used to assess quality of life before and after surgery. RESULTS: A total of 21 patients (14 female and 7 male) underwent treatment as specified. Eighty-five percent (17/20) of the patients reported prolonged remission of symptoms (mean follow-up period = 4.15 years). Five percent (1/20) reported occasional recurrence of twitches. The overall mean quality of life score improved from 11.1 preoperatively to 2.2 postoperatively. CONCLUSIONS: MVD offers significant and prolonged improvement in quality of life for the HFS patients we studied, as measured using a disease-specific, validated quality of life assessment scale. Postoperative quality of life, however, was strongly influenced by both the success of surgery in resolving the symptoms and the absence of any permanent complications of surgery.

Gamma Knife radiosurgery for trigeminal neuralgia: the impact of magnetic resonance imaging-detected vascular impingement of the affected nerve.

OBJECT: Trigeminal neuralgia is believed to be related to vascular compression of the affected nerve. Radiosurgery has been shown to be reasonably effective for treatment of medically refractory trigeminal neuralgia. This study explores the rate of occurrence of MR imaging-demonstrated vascular impingement of the affected nerve and the extent to which vascular impingement affects pain relief in a population of trigeminal neuralgia patients undergoing Gamma Knife radiosurgery (GKRS). METHODS: The authors performed a retrospective analysis of 106 cases involving patients treated for typical trigeminal neuralgia using GKRS. Patients with or without single-vessel impingement on CISS MR imaging sequences and with no previous surgery were included in the study. Pain relief was assessed according to the Barrow Neurological Institute (BNI) pain intensity score at the last follow-up. Degree of impingement, nerve diameter preand post-impingement, isocenter placement, and dose to the point of maximum impingement were evaluated in relation to the improvement of BNI score. RESULTS: The overall median follow-up period was 31 months. Overall, a BNI pain score of 1 was achieved in 59.4% of patients at last follow-up. Vessel impingement was seen in 63 patients (59%). There was no significant difference in pain relief between those with and without vascular impingement following GKRS (p > 0.05). In those with vascular impingement on MR imaging, the median fraction of vessel impingement was 0.3 (range 0.04-0.59). The median dose to the site of maximum impingement was 42 Gy (range 2.9-79 Gy). Increased dose (p = 0.019) and closer proximity of the isocenter to the site of maximum vessel impingement (p = 0.012) correlated in a statistically significant fashion with improved BNI scores in those demonstrating vascular impingement on the GKRS planning MR imaging. CONCLUSIONS: Vascular impingement of the affected nerve was seen in the majority of patients with trigeminal neuralgia. Overall pain relief following GKRS was comparable in those with and without evidence of vascular compression on MR imaging. In subgroup analysis of those with MR imaging evidence of vessel impingement of the affected trigeminal nerve, pain relief correlated with a higher dose to the point of contact between the impinging vessel and the trigeminal nerve. Such a finding may point to vascular changes affording at least some degree of relief following GKRS for trigeminal neuralgia.

Gamma knife surgery for lymphocytic hypophysitis.

Lymphocytic hypophysitis is a relatively uncommon autoimmune inflammatory disorder affecting the pituitary gland. It most frequently occurs in women of child-bearing age. The authors report on their experience with a patient who presented with diplopia and marked enlargement of the pituitary gland. She underwent transsphenoidal surgery, and histopathological analysis confirmed the diagnosis of lymphocytic hypophysitis. The disease proved refractory to resection, and any attempt at withdrawal of corticosteroid therapy resulted in a return of the patient's symptoms and enlargement of the sellar contents. The patient underwent Gamma Knife surgery (GKS) to the sella and both cavernous sinuses. After GKS, the patient was able to discontinue steroid therapy without return of her symptoms. Follow-up MR images demonstrated no evidence of recurrence of lymphocytic hypophysitis. For persistent lymphocytic hypophysitis, GKS is a reasonable treatment option.

Gamma Knife radiosurgery to the surgical cavity following resection of brain metastases.

OBJECT: This study evaluated the efficacy of postoperative Gamma Knife surgery (GKS) to the tumor cavity following gross-total resection of a brain metastasis. METHODS: A retrospective review was conducted of 700 patients who were treated for brain metastases using GKS. Forty-seven patients with pathologically confirmed metastatic disease underwent GKS to the postoperative resection cavity following gross-total resection of the tumor. Patients who underwent subtotal resection or who had visible tumor in the resection cavity on the postresection neuroimaging study (either CT or MR imaging with and without contrast administration) were excluded. Radiographic and clinical follow-up was assessed using clinic visits and MR imaging. The radiographic end point was defined as tumor growth control (no tumor growth regarding the resection cavity, and stable or decreasing tumor size for the other metastatic targets). Clinical end points were defined as functional status (assessed prospectively using the Karnofsky Performance Scale) and survival. Primary tumor pathology was consistent with lung cancer in 19 cases (40%), melanoma in 10 cases (21%), renal cell carcinoma in 7 cases (15%), breast cancer in 7 cases (15%), and gastrointestinal malignancies in 4 cases (9%). The mean duration between resection and radiosurgery was 15 days (range 2-115 days). The mean volume of the treated cavity was 10.5 cm3 (range 1.75-35.45 cm3), and the mean dose to the cavity margin was 19 Gy. In addition to the resection cavity, 34 patients (72%) underwent GKS for 116 synchronous metastases observed at the time of the initial radiosurgery. RESULTS: The mean radiographic follow-up duration was 14 months (median 10 months, range 4-37 months). Local tumor control at the site of the surgical cavity was achieved in 44 patients (94%), and tumor recurrence at the surgical site was statistically related to the volume of the surgical cavity (p=0.04). During follow-up, 34 patients (72%) underwent additional radiosurgery for 140 new (metachronous) metastases. At the most recent follow-up evaluation, 11 patients (23%) were alive, whereas 36 patients had died (mean duration until death 12 months, median 10 months). Patients who showed good systemic control of their primary tumor tended to have longer survival durations than those who did not (p=0.004). At the last clinical follow-up evaluation, the mean Karnofsky Performance Scale score for the overall group was 78 (median 80, range 40-100). CONCLUSION: Radiosurgery appears to be effective in terms of providing local tumor control at the resection cavity following resection of a brain metastasis, and in the treatment of synchronous and metachronous tumors. These data suggest that radiosurgery can be used to prevent recurrence following gross-total resection of a brain metastasis.

Lennart Heimer: concepts of the ventral striatum and extended amygdala.

Dr. Lennart Heimer, the famous neuroanatomist of Swedish descent, died last year but left a legacy that will impact the neurosciences and potentially psychosurgery for years to come. He developed an anatomical technique for demonstrating the terminal boutons that helped to delineate basal forebrain anatomy. During these studies, he realized the relationship of basal forebrain structures to the limbic system, thus initiating the concept of the ventral striatum and parallel basal ganglia circuitry. Heimer excelled as a teacher as well and honed his brain dissection technique to one of the most effective tools for understanding neuroanatomy. His legendary sessions with neurosurgical residents resulted in his recognition as one of the world's leading fiber tract dissectors. His gentle, engaging manner has been documented in several media formats.

Brain abscess in children.

Although it is uncommon, pediatric brain abscess remains a serious, life-threatening neurological problem. Those with congenital heart disease, an ongoing infection, or an immunocompromised state are particularly at risk. The symptoms on presentation may include those associated with a space-occupying lesion in the brain, and neuroimaging has made the diagnosis of brain abscess more reliable. Prompt diagnosis and treatment are required to lessen neurological morbidity and the risk of death. Treatment includes medical management with appropriate and specific antimicrobials. Although the effectiveness of medical management has improved and some children may be treated with antimicrobial therapy alone, surgical evaluation remains an important component of the treatment algorithm for most pediatric patients.