Long noncoding RNA

Long noncoding RNA

Long non-coding RNAs (long ncRNAs, lncRNA) are non-protein coding transcripts longer than 200 nucleotides.

This somewhat arbitrary limit distinguishes long ncRNAs from small regulatory RNAs such as microRNAs (miRNAs), short interfering RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and other short RNAs.

They participate extensively in biological processes of various cancers. The majority of these transcripts are uniquely expressed in differentiated tissues or specific cancer types 1).

Emerging evidence reveal that long noncoding RNAs (lncRNAs) participates in the epigenetic regulation of pathophysiological process.

Long noncoding RNAs (lncRNAs) have been proposed as promoter or inhibitor in many cancer processes.

LncRNAs are involved in many cellular processes, such as angiogenesis, invasion, cell proliferation, and apoptosis.


Genome-wide transcriptional studies have demonstrated that tens of thousands of lncRNA genes are expressed in the CNS and that they exhibit tissue– and cell-type specificity. Their regulated and dynamic expression, and their co-expression with protein-coding gene neighbours, have led to the study of the functions of lncRNAs in CNS development and disorders.

In a review, Cuevas-Diaz Duran et al., from the Vivian L. Smith Department of Neurosurgery, Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, Tecnologico de Monterrey, describe the general characteristics, localization, and classification of lncRNAs. They also elucidate examples of the molecular mechanisms of nuclear and cytoplasmic lncRNA actions in the CNS and discuss common experimental approaches used to identify and unveil the functions of lncRNAs. Additionally, they provide examples of lncRNA studies of cell differentiation and CNS disorders including CNS injuries and neurodegenerative diseases. Finally, they review novel lncRNA-based therapies. Overall, this review highlights the important biological roles of lncRNAs in CNS functions and disorder2).

Importance

see Long noncoding RNA in glioma.

see Long noncoding RNA in meningioma.

see Circular RNAs (circRNAs) are highly stable, circularized long noncoding RNAs.

see also Long noncoding RNA MALAT1.


Long non-coding RNAs (lncRNAs) have received increased research interest owing to their participation via distinct mechanisms in the biological processes of clinically nonfunctioning pituitary adenomas. However, changes in the expression of lncRNAs in gonadotrophin adenoma, which is the most common nonfunctional pituitary adenomas, have not yet been reported. In this study, we performed a genome-wide analysis of lncRNAs and mRNAs obtained from gonadotrophin adenoma patients’ samples and normal pituitary tissues using RNA-seq. The differentially expressed lncRNAs and mRNAs were identified using fold-change filtering. We identified 839 lncRNAs and 1015 mRNAs as differentially expressed. Gene Ontology analysis indicated that the biological functions of differentially expressed mRNAs were related to transcription regulator activity and basic metabolic processes. Ingenuity Pathway Analysis was performed to identify 64 canonical pathways that were significantly enriched in the tumor samples. Furthermore, to investigate the potential regulatory roles of the differentially expressed lncRNAs on the mRNAs, we constructed general co-expression networks for 100 coding and 577 non-coding genes that showed significantly correlated expression patterns in tumor cohort. In particular, we built a special sub-network of co-expression involving 186 lncRNAs interacting with 15 key coding genes of the mTOR pathway, which might promote the pathogenesis of gonadotrophin tumor. This is the first study to explore the patterns of genome-wide lncRNAs expression and co-expression with mRNAs, which might contribute to the molecular pathogenesis of gonadotrophin adenoma 3).

References

1)

Chen L, Zhang YH, Lu G, Huang T, Cai YD. Analysis of cancer-related lncRNAs using gene ontology and KEGG pathways. Artif Intell Med. 2017 Feb;76:27-36. doi: 10.1016/j.artmed.2017.02.001. Epub 2017 Feb 13. PubMed PMID: 28363286.
2)

Cuevas-Diaz Duran R, Wei H, Kim DH, Wu JQ. Long non-coding RNAs: important regulators in the development, function, and disorders of the central nervous system. Neuropathol Appl Neurobiol. 2019 Jan 13. doi: 10.1111/nan.12541. [Epub ahead of print] PubMed PMID: 30636336.
3)

Li J, Li C, Wang J, Song G, Zhao Z, Wang H, Wang W, Li H, Li Z, Miao Y, Li G, Zhang Y. Genome-wide analysis of differentially expressed lncRNAs and mRNAs in primary gonadotrophin adenomas by RNA-seq. Oncotarget. 2016 Dec 15. doi: 10.18632/oncotarget.13948. [Epub ahead of print] PubMed PMID: 27992366.

Brainstem Anatomy for Neurosurgeons

Brainstem Anatomy for Neurosurgeons

January 14 — January 15

ZurichSwitzerland

https://usz-microsite.ch/anatomiekurse/wp-content/uploads/sites/50/2018/12/PF_Brainstem-Anatomy_Digital.pdf

3rd Hands-On Training with Skull Model and Brain Cadaver Brainstem Anatomy for Neurosurgeons

Course Director: PD Dr. med. Oliver Bozinov

Monday 14th and Tuesday 15th of January 2019 Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057 Zurich

Lectures on brainstem anatomy, lesions and approaches will be held also at the prior brainstem conference (www.brainstem-conference.com).

Credits 12

Inflow angle

Inflow angle

The angle separating parent vessel and aneurysm dome main axes.

Maximal intracranial aneurysm size and intracranial aneurysm morphology parameters are used when deciding if an Intracranial aneurysm (IA) should be treated prophylactically. These parameters are derived from postrupture morphology. As time and rupture may alter the aneurysm geometry, possible morphological predictors of a Ruptured intracranial aneurysm should be established in prerupture aneurysms.

Skodvin et al., from University Hospital of Northern NorwayOslo University Hospital Rikshospitalet matched 1:2 with 24 control IAs that remained unruptured during a median follow-up time of 4.5 (interquartile range, 3.7-8.2) yr. Morphological parameters were automatically measured on 3-dimensional models constructed from angiograms obtained at time of diagnosis. Cases and controls were matched by aneurysm location and aneurysm size, patient age and sex, and the PHASES score (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage from another aneurysm, and site of aneurysm) did not differ between the 2 groups.

Only inflow angle was significantly different in cases vs controls in univariate analysis (P = .045), and remained significant in multivariable analysis. Maximal size correlated with size ratio in both cases and controls (P = .015 and <.001, respectively). However, maximal size and inflow angle were correlated in cases but not in controls (P = .004. and .87, respectively).

A straighter inflow angle may predispose an aneurysm to changes that further increase risk of rupture. Traditional parameters of aneurysm morphology may be of limited value in predicting IA rupture 1).


In 2016 Ji et al., concluded that unruptured paraclinoid aneurysms had a high incidence of aneurysm recanalization (AR) after endovascular treatment. An inflow angle of ≥90 degrees and incomplete occlusion were significant predictors of AR 2).


In 2010 the objective of Baharoglu et al., was to evaluate the importance of inflow-angle (IA), the angle separating parent vessel and aneurysm dome main axes.

IA, maximal dimension, height-width ratio, and dome-neck aspect ratio were evaluated in sidewall-type aneurysms with respect to rupture status in a cohort of 116 aneurysms in 102 patients. Computational fluid dynamic analysis was performed in an idealized model with variational analysis of the effect of IA on intra-aneurysmal hemodynamics.

Univariate analysis identified IA as significantly more obtuse in the ruptured subset (124.9 degrees+/-26.5 degrees versus 105.8 degrees+/-18.5 degrees, P=0.0001); similarly, maximal dimension, height-width ratio, and dome-neck aspect ratio were significantly greater in the ruptured subset; multivariate logistic regression identified only IA (P=0.0158) and height-width ratio (P=0.0017), but not maximal dimension or dome-neck aspect ratio, as independent discriminants of rupture status. Computational fluid dynamic analysis showed increasing IA leading to deeper migration of the flow recirculation zone into the aneurysm with higher peak flow velocities and a greater transmission of kinetic energy into the distal portion of the dome. Increasing IA resulted in higher inflow velocity and greater wall shear stress magnitude and spatial gradients in both the inflow zone and dome.

They concluded that Inflow-angle is a significant discriminant of rupture status in sidewall-type aneurysms and is associated with higher energy transmission to the dome. These results support inclusion of IA in future prospective aneurysm rupture risk assessment trials 3).

References

1)

Skodvin TØ, Evju Ø, Sorteberg A, Isaksen JG. Prerupture Intracranial Aneurysm Morphology in Predicting Risk of Rupture: A Matched Case-Control Study. Neurosurgery. 2019 Jan 1;84(1):132-140. doi: 10.1093/neuros/nyy010. PubMed PMID: 29529238.
2)

Ji W, Liu A, Lv X, Sun L, Liang S, Li Y, Yang X, Jiang C, Wu Z. Larger inflow angle and incomplete occlusion predict recanalization of unruptured paraclinoid aneurysms after endovascular treatment. Interv Neuroradiol. 2016 Aug;22(4):383-8. doi: 10.1177/1591019916641315. Epub 2016 Apr 11. PubMed PMID: 27066815; PubMed Central PMCID: PMC4984388.
3)

Baharoglu MI, Schirmer CM, Hoit DA, Gao BL, Malek AM. Aneurysm inflow-angle as a discriminant for rupture in sidewall cerebral aneurysms: morphometric and computational fluid dynamic analysis. Stroke. 2010 Jul;41(7):1423-30. doi: 10.1161/STROKEAHA.109.570770. Epub 2010 May 27. PubMed PMID: 20508183.

Raman spectroscopy

Raman spectroscopy

Raman spectroscopy named after Indian physicist Sir C. V. Raman is a spectroscopic technique used to observe vibrational, rotational, and other low-frequency modes in a system.

Raman spectroscopy is commonly used in chemistry to provide a structural fingerprint by which molecules can be identified.


Navigation-guided brain biopsies are the standard of care for diagnosis of several brain pathologies. However, imprecise targeting and tissue heterogeneity often hinder obtaining high-quality tissue samples, resulting in poor diagnostic yield.

Raman histology has potential for detecting viable tumor in biopsied tissue and for identifying tumor infiltration in vivo 1).

Desroches et al., from the Montreal Neurological Institute and Hospital, report the development and first clinical testing of a navigation-guided fiberoptic Raman probe that allows surgeons to interrogate brain tissue in situ at the tip of the biopsy needle, prior to tissue removal. The 900μm diameter probe can detect high spectral quality Raman signals in both the fingerprint and high wavenumber spectral regions with minimal disruption to the neurosurgical workflow. The probe was tested in 3 brain tumor patients, and the acquired spectra in both normal brain and tumor tissue demonstrated the expected spectral features, indicating the quality of the data. As a proof-of-concept, they also demonstrate the consistency of the acquired Raman signal with different systems and experimental settings. Additional clinical development is planned to further evaluate the performance of the system and develop a statistical model for real-time tissue classification during the biopsy procedure 2).


The aim of a study was to use Raman spectroscopy to analyze the biochemical composition of medulloblastoma and normal tissues from the safety margin of the CNS and to find specific Raman biomarkers capable of differentiating between tumorous and normal tissues.

The tissue samples consisted of medulloblastoma (grade IV) (n = 11). The tissues from the negative margins were used as normal controls. Raman images were generated by a confocal Raman microscope-WITec alpha 300 RSA.

Raman vibrational signatures can predict which tissue has tumorous biochemistry and can identify medulloblastoma. The Raman technique makes use of the fact that tumors contain large amounts of protein and far less lipids (fatty compounds), while healthy tissue is rich in both.

The ability of Raman spectroscopy and imaging to detect medulloblastoma tumors fills the niche in diagnostics. These powerful analytical techniques are capable of monitoring tissue morphology and biochemistry. The results demonstrate that RS can be used to discriminate between normal and medulloblastoma tissues 3).

References

1)

Hollon T, Stummer W, Orringer D, Suero Molina E. Surgical Adjuncts to Increase the Extent of Resection: Intraoperative MRI, Fluorescence, and Raman Histology. Neurosurg Clin N Am. 2019 Jan;30(1):65-74. doi: 10.1016/j.nec.2018.08.012. Review. PubMed PMID: 30470406.
2)

Desroches J, Lemoine É, Pinto M, Marple E, Urmey K, Diaz R, Guiot MC, Wilson BC, Petrecca K, Leblond F. Development and first in-human use of a Raman spectroscopy guidance system integrated with a brain biopsy needle. J Biophotonics. 2019 Jan 12. doi: 10.1002/jbio.201800396. [Epub ahead of print] PubMed PMID: 30636032.
3)

Polis B, Imiela A, Polis L, Abramczyk H. Raman spectroscopy for medulloblastoma. Childs Nerv Syst. 2018 Jul 12. doi: 10.1007/s00381-018-3906-7. [Epub ahead of print] PubMed PMID: 30003328; PubMed Central PMCID: PMC6224026.

Esthesioneuroblastoma

Esthesioneuroblastoma (ENB)

AKA: Olfactory neuroblastoma.

Esthesioneuroblastoma is a rare malignant tumor of sinonasal origin. These tumors typically present with unilateral nasal obstruction and epistaxis, and diagnosis is confirmed on biopsy.

Treatment

Case series

Nineteen patients from Brescia received endoscopic resection with transnasal craniectomy and subpial dissection (ERTC-SD) and 11 had pathological-proven brain invasion. Histologies were 6 olfactory neuroblastomas (ONB), 3 neuroendocrine carcinomas, and 2 intestinal-type adenocarcinomas. Mean follow-up was 21.9 months. Three-year overall, local recurrence-free, and distance recurrence-free survivals were 65.5%, 81.8%, and 68.2%, respectively. Overall and distant recurrence-free survivals were significantly better in patients with ONB (P = 0.032 and P = 0.013, respectively). Hospitalization ratio was 4.1%. Complication rate was 10.5%.

In selected nasal-ethmoidal tumors with brain invasion, ERTC-SD can provide good local control, satisfactory survival, and limited morbidity 1).


Klironomos et al., presented the use of pure EEA in the management of ENB in the Toronto Western Hospital, along with a literature review. They retrospectively reviewed the clinical, radiology and pathology records of patients with ENB treated during the period July 2006 to January 2016. During the above period, ten patients with ENB were treated using pure EEA. The mean age was 47.5 years. The gender distribution was: eight males, two females. The most common presenting symptoms were nasal obstruction and discharge or epistaxis (8/10). The mean duration of symptoms was 1.5 years. All patients had preoperative confirmation of ENB by biopsy. Five patients received neoadjuvant radiation and four underwent postoperative radiation. One patient did not receive any radiotherapy and no patient received chemotherapy. Gross total resection was achieved in all patients and intraoperative microscopically negative surgical margins achieved in 9/10 (90%). No major intraoperative complications occurred. The most common postoperative complication was nasal infection. Cerebrospinal fluid leak was noted in one patient. During the follow-up period of 6-120 months (mean 74.8) two cases of neck lymph node recurrence were observed. No deaths due to the disease occurred during the follow-up period. Pure EEA offer excellent results in the management of ENB. Neoadjuvant radiation treatment is promising although more studies need to establish its role 2).


There is a scarcity of data about different treatment strategies. Intensity modulated radiotherapy (IMRT) and carbon ion radiotherapy (CIRT) are advanced radiation techniques that might improve local tumor control.

In a retrospective analysis of 17 patients with ENB (Kadish stage ≥ C: 88%; n = 15). Four patients had already undergone previous radiotherapy (RT). The treatment consisted of either IMRT (n = 5), CIRT (n = 4) or a combination of both techniques (n = 8). Median follow-up was 29 months. (3) Results: In patients that had not been irradiated before (n = 13), calculated overall survival (OS) and progression free survival (PFS) rates after 48 months were 100% and 81% respectively (Kaplan-Meier estimates). Two of four patients that underwent reirradiation died after RT, presumably due to tumor progression. Besides common toxicities, five patients (30%) showed mostly asymptomatic radiation-induced brain changes, most likely due to a disturbance of the blood-brain barrier.

The results demonstrate that IMRT, CIRT, a combined approach of IMRT and CIRT as well as reirradiation with CIRT seem to be feasible and effective treatment methods in ENB. 3).


ENB is safely and effectively treated with craniofacial resection (CFR) followed by proton beam irradiation. The high incidence of regional metastases warrants strong consideration for elective neck irradiation. Proton beam radiation is associated with lower rates of severe late-radiation toxicity than conventional radiotherapy 4).


The National Cancer Database (NCDB) was used to identify patients diagnosed with ENB between 2004 to 2015. Patients were excluded based on the ability to properly stage their disease as well as the availability of treatment data.

Eight-hundred eighty-three patients had sufficient data for analysis. On multivariate analysis, age and government insurance were associated with primary surgical treatment, whereas tumor stage, gender, race, hospital type and volume, and comorbidity score were not. Age, charlson-deyo comorbidity (CDCC) score, hospital volume, and nodal status were found to be predictors of survival. Multivariate-analysis controlling for stage failed to demonstrate clear survival differences between staging in both TNM and Kadish systems. T-stage and the presence of regional nodal metastasis were associated with an increased risk of positive margins on multivariate analysis.

Although primary surgical management and positive margins can be predicted by certain patient and tumor factors, clinical staging systems for ENB poorly predict prognosis over a 10-year horizon 5).

Esthesioneuroblastoma case reports

A case of non-contiguous meningeal recurrence of olfactory neuroblastoma presenting as a giant frontal mass. A 66-year-old woman was admitted with a left nasal intranasal localized tumor without cranial extension and gross total removal was achieved. Pathological examination showed olfactory neuroblastoma and radiation therapy was added in a limited region of the removal cavity. Radiological follow-up continued for 10 years and there was no local recurrence. Sixteen years after radiation therapy, the patient found a slight frontal mass gradually growing. Magnetic resonance imaging revealed an enhanced mass lesion of 7 cm in thickness and 9 cm in diameter associated with marked thickness of the frontal bone, intradural cystic mass compressing the bilateral frontal lobe, and no local recurrence. A second operation was performed followed by radiotherapy and we diagnosed no-contiguous meningeal recurrence of metastatic olfactory neuroblastoma. Olfactory neuroblastoma is a locally aggressive tumor. Although metastasis of this tumor has been reported, non-contiguous spread to the dura is rare. Understanding the route of remote metastasis and careful evaluation after primary treatment are needed to avoid misdiagnosis and treatment delays 6).

References

1)

Mattavelli D, Ferrari M, Bolzoni Villaret A, Schreiber A, Rampinelli V, Turri-Zanoni M, Lancini D, Taglietti V, Accorona R, Doglietto F, Battaglia P, Castelnuovo P, Nicolai P. Transnasal endoscopic surgery in selected nasal-ethmoidal cancer with suspected brain invasion: Indications, technique, and outcomes. Head Neck. 2019 Jan 12. doi: 10.1002/hed.25621. [Epub ahead of print] PubMed PMID: 30636181.
2)

Klironomos G, Gonen L, Au K, Monteiro E, Mansouri A, Turel MK, Witterick I, Vescan A, Zadeh G, Gentili F. Endoscopic management of Esthesioneuroblastoma: Our experience and review of the literature. J Clin Neurosci. 2018 Dec;58:117-123. doi: 10.1016/j.jocn.2018.09.011. Epub 2018 Oct 16. Review. PubMed PMID: 30340976.
3)

Liermann J, Syed M, Held T, Bernhardt D, Plinkert P, Jungk C, Unterberg A, Rieken S, Debus J, Herfarth K, Adeberg S. Advanced Radiation Techniques in the Treatment of Esthesioneuroblastoma: A 7-Year Single-Institution’s Clinical Experience. Cancers (Basel). 2018 Nov 20;10(11). pii: E457. doi: 10.3390/cancers10110457. PubMed PMID: 30463343; PubMed Central PMCID: PMC6267306.
4)

Herr MW, Sethi RK, Meier JC, Chambers KJ, Remenschneider A, Chan A, Curry WT, Barker FG 2nd, Deschler DG, Lin DT. Esthesioneuroblastoma: an update on the massachusetts eye and ear infirmary and massachusetts general hospital experience with craniofacial resection, proton beam radiation, and chemotherapy. J Neurol Surg B Skull Base. 2014 Feb;75(1):58-64. doi: 10.1055/s-0033-1356493. Epub 2013 Sep 20. PubMed PMID: 24498591.
5)

Joshi RR, Husain Q, Roman BR, Cracchiolo J, Yu Y, Tsai J, Kang J, McBride S, Lee NY, Morris L, Ganly I, Tabar V, Cohen MA. Comparing Kadish, TNM, and the modified Dulguerov staging systems for esthesioneuroblastoma. J Surg Oncol. 2019 Jan;119(1):130-142. doi: 10.1002/jso.25293. Epub 2018 Nov 22. PubMed PMID: 30466166.
6)

Saito A, Sasaki T, Inoue T, Narisawa A, Inoue T, Suzuki S, Ezura M, Uenohara H. Non-contiguous Meningeal Recurrence of Olfactory Neuroblastoma: A Case Report and Literature Review. NMC Case Rep J. 2018 Jun 28;5(3):69-72. doi: 10.2176/nmccrj.cr.2017-0233. eCollection 2018 Jul. PubMed PMID: 30023143; PubMed Central PMCID: PMC6048349.

Hypoxic ischaemic brain injury

Hypoxic ischaemic brain injury

Hypoxic ischaemic brain injury is common and usually due to cardiac arrest or profound hypotension. The clinical pattern and outcome depend on the severity of the initial insult, the effectiveness of immediate resuscitation and transfer, and the post-resuscitation management on the intensive care unit. Clinical assessment is difficult and so often these days compromised by sedationneuromuscular-blocking drugventilationhypothermia and inotropic management. Investigations can add valuable information, in particular brain MRI shows characteristic patterns depending on the severity of the injury and the timing of imaging. EEG patterns may also suggest the possibility of a good outcome. There is no entirely reliable algorithm of clinical signs or investigations which allow a definitive prognosis but the combination of careful repeated observations and appropriate ancillary investigations allows the neurologist to give an informed and accurate opinion of the likely outcome, and to advise on management. Overall, the prognosis is extremely poor and only a quarter of patients survive to hospital discharge, and often even then with severe neurological or cognitive deficits 1).


In eleven patients (median age of 47 [range 20-71], 8 male and 3 female). There was a linear relationship between ICP and non-invasive estimators of ICP (nICP) with optic nerve sheath diameter ultrasonography (ONSD) (R = 0.53 [p < 0.0001]), JVP (R = 0.38 [p < 0.001]) and transcranial Doppler ultrasonography (TCD) (R = 0.30 [p < 0.01]). The ability to predict intracranial hypertension was highest for ONSD and TCD (AUC = 0.96 [95% CI: 0.90-1.00] and AUC = 0.91 [95% CI: 0.83-1.00], respectively). Jugular venous bulb pressure (JVP). presented the weakest prediction ability (AUC = 0.75 [95% CI: 0.56-0.94]).

ONSD and TCD methods demonstrated agreement with invasively-monitored ICP, suggesting their potential roles in the detection of intracranial hypertension in hypoxic ischaemic brain injury (HIBI) after cardiac arrest 2).

References

1)

Howard RS, Holmes PA, Koutroumanidis MA. Hypoxic-ischaemic brain injury. Pract Neurol. 2011 Feb;11(1):4-18. doi: 10.1136/jnnp.2010.235218. Review. PubMed PMID: 21239649.
2)

Cardim D, Griesdale DE, Ainslie PN, Robba C, Calviello L, Czosnyka M, Smielewski P, Sekhon MS. A comparison of non-invasive versus invasive measures of intracranial pressure in hypoxic ischaemic brain injury after cardiac arrest. Resuscitation. 2019 Jan 7. pii: S0300-9572(18)30912-2. doi: 10.1016/j.resuscitation.2019.01.002. [Epub ahead of print] PubMed PMID: 30629992.

Breast cancer pituitary metastases

Breast cancer pituitary metastases

Tumors that metastasize to the pituitary gland are unusual, and are typically seen in elderly patients with diffuse malignant disease. The most common metastases to the pituitary are from primary breast and lung cancers.

Cai et al., from Shengjing Hospital of China Medical University, Shenyangpresented a 57 year-old patient with pituitary gland metastasis from breast cancer that was treated with extensive radical mastectomy 16 years prior. The pituitary was the sole site of metastasis. The patient was admitted with the chief complaint of blurred vision for 1 year and episodic headaches for 1 month. Magnetic resonance imaging revealed a solid mass in the sellar region with heterogenous contrast enhancement. The preoperative diagnosis was a pituitary adenomaNeuroendoscopy-assisted tumor resection was conducted through a single-nostril sphenoid sinus approach. A pinkish-white, firm neoplasm was found, with an abundant blood supply and an indistinct boundary between the neoplasm and normal pituitary tissue; complete resection was achieved. The results of immunohistochemical analysis were positive for cytokeratinKi-67antigen, estrogen receptors, progesterone receptors, and prolactin induced protein. The neoplasm was negative for SALL4mammaglobin, and the Glycoprotein hormones, alpha polypeptide. These results were used to reach a final diagnosis of a pituitary gland metastasis from a primary breast carcinoma. The patient’s vision improved significantly after surgery, and no recurrence was detected during one year of follow-up.

Pituitary gland metastasis is rare and difficult to differentiate from a pituitary adenoma without a pathologic diagnosis. Surgery is the first choice for treatment. Surgery, radiotherapy and chemotherapy are combined with endocrine therapy to tailored treatment to the results of immunohistochemistry 1)


An 83-year-old woman developed pituitary metastasis while being treated for metastatic breast cancer. She presented with visual disturbance and headache followed by thirst, nocturia and polyuria. A visual field defect was present. MRI revealed a sellar mass consistent with metastasis to the pituitary gland. She was successfully treated with radiotherapy to the sella and had improvement of her visual symptoms and visual field defect. She then required ongoing treatment for diabetes insipidus. Her symptoms had not shown any sign of recurring up to 9 months after treatment. Pituitary metastases are rare but should be suspected in patients with metastatic cancer who present with features similar to those seen here. With improvements in survival in metastatic breast cancer, pituitary metastases may be seen more commonly and active local treatment is warranted given the possibility of resolution of symptoms related to the pituitary metastases 2).


Kim et al., reported a 65-year-old woman with pituitary metastasis from breast cancer who presented with recent-onset left progressive deterioration of visual acuity and visual field. The clinical diagnosis was made after brain and sellar magnetic resonance imaging showed a large sellar mass compressing the optic chiasm and invading the pituitary stalk. An otorhinolaryngology and neurosurgery team removed the tumor via a transsphenoidal approach, and this procedure obtained symptomatic relief. Postoperatively, metastasis from breast invasive ductal adenocarcinoma was confirmed histologically. We report this unusual case with a review of the relevant literature 3).


A 55-years-old woman presented with diabetes insipidus resulting from metastasis of the tumor to pituitary infundibulum, which is a rare site for metastasis, without significant complaint resulting from metastasis to other part of the body, or other primary diseases. Further evaluation revealed that in spite of previous reports, which metastasis usually happens in end stage of cancer, the patients had primary breast cancer. In subsequent evaluations of the case, hypofunction of adenohypophysis was also detected 4).

References

1)

Cai H, Liu W, Feng T, Li Z, Liu Y. Clinical Presentation and Pathologic Characteristics of Pituitary Metastasis From Breast Carcinoma: Cases and a Systematic Review of the Literature. World Neurosurg. 2019 Jan 7. pii: S1878-8750(18)32949-8. doi: 10.1016/j.wneu.2018.12.126. [Epub ahead of print] PubMed PMID: 30630045.
2)

Gormally JF, Izard MA, Robinson BG, Boyle FM. Pituitary metastasis from breast cancer presenting as diabetes insipidus. BMJ Case Rep. 2014 Apr 12;2014. pii: bcr2014203683. doi: 10.1136/bcr-2014-203683. PubMed PMID: 24729116; PubMed Central PMCID: PMC3987639.
3)

Kim YH, Lee BJ, Lee KJ, Cho JH. A case of pituitary metastasis from breast cancer that presented as left visual disturbance. J Korean Neurosurg Soc. 2012 Feb;51(2):94-7. doi: 10.3340/jkns.2012.51.2.94. Epub 2012 Feb 29. PubMed PMID: 22500201; PubMed Central PMCID: PMC3322215.
4)

Poursadegh Fard M, Borhani Haghighi A, Bagheri MH. Breast cancer metastasis to pituitary infandibulum. Iran J Med Sci. 2011 Jun;36(2):141-4. PubMed PMID: 23358184; PubMed Central PMCID: PMC3556747.

Deep brain stimulation of the nucleus basalis of Meynert

Deep brain stimulation of the nucleus basalis of Meynert

Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a treatment option for Parkinson disease dementia.

Low-frequency NBM DBS was safely conducted in patients with Parkinson disease dementia; however, no improvements were observed in the primary cognitive outcomes. Further studies may be warranted to explore its potential to improve troublesome neuropsychiatric symptoms 1).


Nombela et al., from Hospital Clínico San CarlosToronto Western Hospital, reported a Parkinson’s disease (PD) patient diagnosed with mild cognitive impairment who underwent DBS surgery targeting the Globus pallidus internus (GPi; to treat motor symptoms) and the nucleus basalis of Meynert (NBM; to treat cognitive symptoms) using a single electrode per hemisphere.

Compared to baseline, 2-month follow-up after GPi stimulation was associated with motor improvements, whereas partial improvements in cognitive functions were observed 3 months after the addition of NBM stimulation to GPi stimulation.

This case explores an available alternative for complete DBS treatment in PD, stimulating 2 targets at different frequencies with a single electrode lead 2).


A global experience is emerging for the use of DBS for these conditions, targeting key nodes in the memory circuit, including the fornix and nucleus basalis of Meynert. Such work holds promise as a novel therapeutic approach for one of medicine’s most urgent priorities 3).

A unique feature in the course of both Alzheimer disease (AD) and Parkinson’s dementia (PDD) is basal forebrain degeneration including the latter’s cholinergic projections to the cortex. Neurostimulation of ascending basal forebrain projections of the Nucleus basalis of Meynert (NBM) may, therefore, represent a new strategy for enhancing the residual nucleus basalis output. The relevance of the cholinergic forebrain for brain plasticity has, for instance, been illustrated by the reshaping of auditory receptive fields during and after stimulation of the NBM in the adult brain 4).

Deep brain stimulation of the nucleus basalis of Meynert is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in Alzheimer disease (AD).

A study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status.

Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate.

With a normal body mass index (BMI) at baseline (mean 23.75 kg/m²) and after 1 year (mean 24.59 kg/m²), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman’s rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman’s rho = -0.829, p = 0.042).

Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies 5).

Case series

Case reports

References

1)

Gratwicke J, Zrinzo L, Kahan J, Peters A, Beigi M, Akram H, Hyam J, Oswal A, Day B, Mancini L, Thornton J, Yousry T, Limousin P, Hariz M, Jahanshahi M, Foltynie T. Bilateral Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson Disease Dementia: A Randomized Clinical Trial. JAMA Neurol. 2018 Feb 1;75(2):169-178. doi: 10.1001/jamaneurol.2017.3762. PubMed PMID: 29255885; PubMed Central PMCID: PMC5838617.
2)

Nombela C, Lozano A, Villanueva C, Barcia JA. Simultaneous Stimulation of the Globus Pallidus Interna and the Nucleus Basalis of Meynert in the Parkinson-Dementia Syndrome. Dement Geriatr Cogn Disord. 2019 Jan 10;47(1-2):19-28. doi: 10.1159/000493094. [Epub ahead of print] PubMed PMID: 30630160.
3)

Sankar T, Lipsman N, Lozano AM. Deep brain stimulation for disorders of memory and cognition. Neurotherapeutics. 2014 Jul;11(3):527-34. doi: 10.1007/s13311-014-0275-0. Review. PubMed PMID: 24777384; PubMed Central PMCID: PMC4121440.
4)

Kilgard MP, Merzenich MM. Cortical map reorganization enabled by nucleus basalis activity. Science (1998) 279(5357):1714–810.1126/science.279.5357.1714
5)

Noreik M, Kuhn J, Hardenacke K, Lenartz D, Bauer A, Bührle CP, Häussermann P, Hellmich M, Klosterkötter J, Wiltfang J, Maarouf M, Freund HJ, Visser-Vandewalle V, Sturm V, Schulz RJ. Changes in Nutritional Status after Deep Brain Stimulation of the Nucleus Basalis of Meynert in Alzheimer’s Disease – Results of a Phase I Study. J Nutr Health Aging. 2015;19(8):812-8. doi: 10.1007/s12603-015-0496-x. PubMed PMID: 26412285.

Neurovascular contact in trigeminal neuralgia

While selectively sectioning the pain fibers in trigeminal neuralgia (which usually lie posteriorly) of the trigeminal nerve via an occipital craniectomy Walter Edward Dandy, as quoted in Wilkins, noted that vascular compression of the trigeminal nerve at the pons was a frequent finding 1).

However some patients may present with clinically classical trigeminal neuralgiabut no vascular conflict on MRI or even at surgery. Several factors have been cited as alternative or supplementary factors that may cause neuralgia.

The vessel that most often causes TN is the superior cerebellar artery (SCA), other known offending vessels include the anterior inferior cerebellar artery(AICA) and the vertebrobasilar artery and vein.

Veins as the source of trigeminal neuralgias (TN) lead to controversies. Only a few studies have specifically dealt with venous implication in neurovascular conflicts (NVC).

A study shows the frequent implication of veins not only at TREZ but also at mid-cisternal portion and porus of Meckel cave 2).

Trigeminal neuralgia in pediatric patients is very rare. A case of typical trigeminal neuralgia in a child, demonstrating the pathogenesis of the neurovascular conflict due to subarachnoidal adhesions after meningoencephalitis was reported 3).


It is widely accepted that a neurovascular contact in the cisternal segment of the trigeminal nerve is the primary cause of classical trigeminal neuralgia 4). However, previous studies have cast doubt on this hypothesis because a neurovascular contact was reported to be prevalent on both the symptomatic and the asymptomatic side and therefore suggested that the severity of the neurovascular contact should be taken into account 5)6) 7). The previous studies were limited by small sample size, lack of blinding, MRI was done with low magnetic field strength or study populations were highly selected consisting only of patients from neurosurgical departments.

Grading the neurovascular contact in classical trigeminal neuralgia is scientifically and probably also clinically important. Findings demonstrate that neurovascular contact is highly prevalent on both the symptomatic and asymptomatic sides. Maarbjerg et al., demonstrated that severe neurovascular contact is involved in the aetiology of classical trigeminal neuralgia and that it is caused by arteries located in the root entry zone. Findings also indicate that in some patients with classical trigeminal neuralgia a neurovascular contact is not involved in the aetiology of the disease or may only be a contributing factor in combination with other unknown factors. The degree of neurovascular contact could thus be important when selecting patients for surgery 8).


Jani et al., from the University of Pittsburgh Medical Centerprospectively recruited 27 patients without facial pain who were undergoing microvascular decompression for hemifacial spasm and had undergone high-resolution preoperative MRINeurovascular contact/compression (NVC/C) by artery or vein was assessed both intraoperatively and by MRI, and was stratified into 3 types: simple contact, compression (indentation of the surface of the nerve), and deformity (deviation or distortion of the nerve).

Intraoperative evidence of NVC/C was detected in 23 patients. MRI evidence of NVC/C was detected in 18 patients, all of whom had intraoperative evidence of NVC/C. Thus, there were 5, or 28% more patients in whom NVC/C was detected intraoperatively than with MRI (Kappa = 0.52); contact was observed in 4 of these patients and compression in 1 patient. In patients where NVC/C was observed by both methods, there was agreement regarding the severity of contact/compression in 83% (15/18) of patients (Kappa = 0.47). No patients exhibited deformity of the nerve by imaging or intraoperatively.

There was moderate agreement between imaging and operative findings with respect to both the presence and severity of NVC/C 9).

References

1)

Wilkins RH: Historical perspectives, in Rovit RL, Murali R, Jannetta PJ (eds): Trigeminal Neuralgia. Baltimore: Williams & Wilkins, 1990, pp 1–25
2)

Dumot C, Sindou M. Trigeminal neuralgia due to neurovascular conflicts from venous origin: an anatomical-surgical study (consecutive series of 124 operated cases). Acta Neurochir (Wien). 2015 Jan 22. [Epub ahead of print] PubMed PMID: 25604274.
3)

Solth A, Veelken N, Gottschalk J, Goebell E, Pothmann R, Kremer P. Successful vascular decompression in an 11-year-old patient with trigeminal neuralgia. Childs Nerv Syst. 2008 Jun;24(6):763-6. doi: 10.1007/s00381-008-0581-0. Epub 2008 Feb 22. PubMed PMID: 18293001.
4)

Devor M, Amir R, Rappaport ZH. Pathophysiology of trigeminal neuralgia: the ignition hypothesis. Clin J Pain. 2002 Jan-Feb;18(1):4-13. Review. PubMed PMID: 11803297.
5)

Masur H, Papke K, Bongartz G, Vollbrecht K. The significance of three-dimensional MR-defined neurovascular compression for the pathogenesis of trigeminal neuralgia. J Neurol. 1995 Jan;242(2):93-8. PubMed PMID: 7707097.
6)

Anderson VC, Berryhill PC, Sandquist MA, Ciaverella DP, Nesbit GM, Burchiel KJ. High-resolution three-dimensional magnetic resonance angiography and three-dimensional spoiled gradient-recalled imaging in the evaluation of neurovascular compression in patients with trigeminal neuralgia: a double-blind pilot study, Neurosurgery , 2006, vol. 58 pg. 666-73
7)

Miller JP, Acar F, Hamilton BE, Burchiel KJ. Radiographic evaluation of trigeminal neurovascular compression in patients with and without trigeminal neuralgia, J Neurosurg , 2009a, vol. 110 pg. 627-632
8)

Maarbjerg S, Wolfram F, Gozalov A, Olesen J, Bendtsen L. Significance of neurovascular contact in classical trigeminal neuralgia. Brain. 2015 Feb;138(Pt 2):311-9. doi: 10.1093/brain/awu349. Epub 2014 Dec 24. PubMed PMID: 25541189.
9)

Jani RH, Hughes MA, Gold MS, Branstetter BF, Ligus ZE, Sekula RF Jr. Trigeminal Nerve Compression Without Trigeminal Neuralgia: Intraoperative vs Imaging Evidence. Neurosurgery. 2019 Jan 1;84(1):60-65. doi: 10.1093/neuros/nyx636. PubMed PMID: 29425330.

EANS Basic Spine Course

January 10, 2019 — January 11, 2019

LyonFrance

Message from Course Chairmen Prof. Torstein R. Meling and Prof. Cédric Barrey:

It is our pleasure to welcome you to the inaugural EANS Spinal Step II Hands-On Course in Lyon. The event will be held from January 10th – 11th 2019 and is organized in the Laboratoire d’Anatomie de la Faculté de Médecine de Lyon.

This dissection course is most suitable for neurosurgical residents in their last years of training as it will focus on the essential neurosurgical anatomy, the planning of surgical procedures, the handling of neurosurgical equipment, and the advanced neurosurgical spinal approaches.

This course will be limited to 24 participants.

Course dates: 10-11 January 2019

For more information please contact petra.koubova@eans.org.

Venue: Département Universitaire d’Anatomie, Faculté de Médecine Lyon Est, 8 avenue Rockefeller, 69373 Lyon Cedex 08

Curriculum: Participants will learn essential neurosurgical anatomy, planning of surgical procedures, handling of neurosurgical equipment, and advanced neurosurgical spinal approaches.

Preliminary programme available HERE.

Registration fees:
EANS Individual Member: €700
Non-Member: €800

The registration fee includes all tuition costs, subsitence during the course, two night accommodation and one networking event.

Accommodation:
Lagrange City Apparthotel
Lyon Lumiere
81-85, cours Albert Thomas
69003 LYON
France

View: The hotel website

NB: This is course is not part of the EUROSPINE equivalence programme. 

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