SagittalMeter Pro

A study of Lee et al., from the Department of Neurosurgery, St. Vincent`s Hospital, Catholic University of Korea, SuwonGangneung Asan HospitalSouth Korea aimed to compare the validityreproducibilityprecision, and efficiency of a picture archiving and communication system (PACS) and a smartphone application which is an educative app to easily measure sagittal balance parameters (SagittalMeter Pro) for measuring spinopelvicsagittal parameters.

Three spine surgeons measured lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), and pelvic tilt (PT) on standing postero-anterior radiographs of 30 patients using PACS and SagittalMeter Pro. Measurements were repeated a week after original measurements. Intra-observer and inter-observer variabilities and reliabilities of each parameter (LL, PI, SS, and PT) were calculated for both techniques. Comparisons were performed using the paired t test. Results are expressed as means ± SDs and p values of <0.05 were considered significant.

PACS to SagittalMeter Pro differences between the mean absolute values of LL, PI, SS, PT were 0.50°, 0.82°, 0.81°, 0.34°, respectively, and intra- and inter- observer variabilities were similar. Excellent intra- and inter- observer reliabilities were obtained for PACS and SagittalMeter Pro as demonstrated by values greater than 0.86 and 0.84, respectively. Measurement times for PACS and SagittalMeter Pro were 36.63±7.55 and 14.57±1.96 seconds, respectively, and this difference was significant (p=0.001).

The study shows PACS and SagittalMeter Pro are equivalent in terms of their abilities to measure spinopelvic sagittal parameters, and that the time required to take measurements was significantly less for SagittalMeter Pro. We believe SagittalMeter Pro may be helpful when planning spinal surgery 1).

1)

Lee JB, Kim IS, Lee JJ, Park JH, Cho CB, Yang SH, Sung JH, Hong JT. Validity of a smartphone application (SagittalMeter Pro) for the measurement of sagittal balance parameters. World Neurosurg. 2018 Dec 14. pii: S1878-8750(18)32808-0. doi: 10.1016/j.wneu.2018.11.242. [Epub ahead of print] PubMed PMID: 30557655.

Multiomics

Multiomics refers to a biological analysis approach in which the data sets are multiple “omes”, such as the genomeproteometranscriptomeepigenome, and microbiome; in other words, the use of multiple omics technologies to study life in a concerted way.


No single-omic approach completely elucidates the multitude of alterations taking place in Alzheimer’s disease (AD).

Marttinen et al., from Kuopio, coupled transcriptomics and phosphoproteomics approach to determine the temporal sequence of changes in mRNA, protein, and phosphopeptides expression level from human temporal cortical samples, with varying degree of AD-related pathology. This approach highlighted fluctuation in synaptic and mitochondrial function as the earliest pathological events in brain samples with AD-related pathology. Subsequently, increased expression of inflammation and extracellular matrix-associated gene products was observed. Interaction network assembly for the associated gene products, emphasized the complex interplay between these processes and the role of addressing post-translational modifications in the identification of key regulators. Additionally, they evaluated the use of decision trees and random forests in identifying potential biomarkers differentiating individuals with different degree of AD-related pathology. This multiomic and temporal sequence-based approach provides a better understanding of the sequence of events leading to AD 1).

1)

Marttinen M, Paananen J, Neme A, Mitra V, Takalo M, Natunen T, Paldanius KMA, Mäkinen P, Bremang M, Kurki MI, Rauramaa T, Leinonen V, Soininen H, Haapasalo A, Pike I, Hiltunen M. A multiomic approach to characterize the temporal sequence in Alzheimer’s disease-related pathology. Neurobiol Dis. 2018 Dec 14. pii: S0969-9961(18)30479-0. doi: 10.1016/j.nbd.2018.12.009. [Epub ahead of print] PubMed PMID: 30557660.

Anterior temporal lobectomy (ATL)

Anterior temporal lobectomy for mesial temporal sclerosis is a very effective measure to control seizures, and the probability of being seizure-free is approximately 70-90%. However, 30% of patients still experience seizures after surgery.

In neurosurgery there are several situations that require transgression of the temporal cortex. For example, a subset of patients with temporal lobe epilepsy require surgical resection (most typically, en-bloc anterior temporal lobectomy). This procedure is the gold standard to alleviate seizures but is associated with chronic cognitive deficits. In recent years there have been multiple attempts to find the optimum balance between minimising the size of resection in order to preserve cognitive function, while still ensuring seizure freedom. Some attempts involve reducing the distance that the resection stretches back from the temporal pole, whilst others try to preserve one or more of the temporal gyri. More recent advanced surgical techniques (selective amygdalohippocampectomy) try to remove the least amount of tissue by going under (sub-temporal), over (trans-Sylvian) or through the temporal lobe (middle-temporal), which have been related to better cognitive outcomes. Previous comparisons of these surgical techniques focus on comparing seizure freedom or behaviour post-surgery, however there have been no systematic studies showing the effect of surgery on white matter connectivity. The main aim of this study, therefore, was to perform systematic ‘pseudo-neurosurgery’ based on existing resection methods on healthy neuroimaging data and measuring the effect on long-range connectivity. We use anatomical connectivity maps (ACM) to determine long-range disconnection, which is complementary to existing measures of local integrity such as fractional anisotropy or mean diffusivity. ACMs were generated for each diffusion scan in order to compare whole-brain connectivity with an ‘ideal resection’, nine anterior temporal lobectomy and three selective approaches. For en-bloc resections, as distance from the temporal pole increased, reduction in connectivity was evident within the arcuate fasciculusinferior longitudinal fasciculusinferior frontooccipital fascicle, and the uncinate fasciculus. Increasing the height of resections dorsally reduced connectivity within the uncinate fasciculus. Sub-temporal amygdalohippocampectomy resections were associated with connectivity patterns most similar to the ‘ideal’ baseline resection, compared to trans-Sylvian and middle-temporal approaches. In conclusion, we showed the utility of ACM in assessing long-range disconnections/disruptions during temporal lobe resections, where we identified the subtemporal resection as the least disruptive to long-range connectivity which may explain its better cognitive outcome. These results have a direct impact on understanding the amount and/or type of cognitive deficit post-surgery, which may not be obtainable using local measures of white matter integrity 1).

Anterior temporal lobectomy (ATL) with amygdalohippocampectomy (ATLAH) has been shown to be more efficacious than continued medical therapy in a randomized, controlled trial 2).

Minimally invasive approaches to treating MTLE might achieve seizure freedom while minimizing adverse effects.

Anterior temporal lobectomy as described by Penfield and Baldwin 3). is the most established neurosurgical procedure for temporal lobe epilepsy, for those in whom anticonvulsant medications do not control epileptic seizures.

It consists in the complete removal of the anterior portion of the temporal lobe of the brain.

Knowledge of the temporomesial region, including neurovascular structures around the brainstem, is essential to keep this procedure safe and effective 4).

The techniques for removing temporal lobe tissue vary from resection of large amounts of tissue, including lateral temporal cortex along with medial structures, to more restricted anterior temporal lobectomy (ATL) to more restricted removal of only the medial structures (selective amygdalohippocampectomy, SAH).

Limits of resection

The measurements are made along the middle temporal gyrus.

Dominant temporal lobe: Up to 4-5 cm may be removed

Non Dominant: 6- 7 cm.


Nearly all reports of seizure outcome following these procedures indicate that the best outcome group includes patients with MRI evidence of mesial temporal sclerosis (hippocampal atrophy with increased T-2 signal.) The range of seizure-free outcomes for these patients is reported to be between 80 and 90%, which is typically reported as a sub-set of data within a larger surgical series.

Open surgical procedures such as ATL have inherent risks including damage to the brain (either directly or indirectly by injury to important blood vessels), bleeding (which can require re-operation), blood loss (which can require transfusion), and infection. Furthermore, open procedures require several days of care in the hospital including at least one night in an intensive care unit. Although such treatment can be costly, multiple studies have demonstrated that ATL in patients who have failed at least two anticonvulsant drug trials (thereby meeting the criteria for medically intractable temporal lobe epilepsy) has lower mortality, lower morbidity and lower long-term cost in comparison with continued medical therapy without surgical intervention.

The strongest evidence supporting ATL over continued medical therapy for medically refractory temporal lobe epilepsy is a prospective, randomized trial of ATL compared to best medical therapy (anticonvulsants), which convincingly demonstrated that the seizure-free rate after surgery was ~ 60% as compared to only 8% for the medicine only group.

Furthermore, there was no mortality in the surgery group, while there was seizure-related mortality in the medical therapy group. Therefore, ATL is considered the standard of care for patients with medically intractable mesial temporal lobe epilepsy.

Surgical resection is the gold standard treatment for drug-resistant focal epilepsy, including mesial temporal lobe epilepsy (MTLE) and other focal cortical lesions with correlated electrophysiological features. Anterior temporal lobectomy with amygdalohippocampectomy (ATLAH) has been shown to be more efficacious than continued medical therapy in a randomized, controlled trial 5).

The most common surgical procedure for the mesial temporal lobe is the standard anterior temporal resection or what is commonly called the anterior temporal lobectomy. There are, however, a number of other more selective procedures for removal of the mesial temporal lobe structures (amygdala, hippocampus, and parahippocampal gyrus) that spare much of the lateral temporal neocortex. Included in these procedures collectively referred to as selective amygdalohippocampectomy are the transsylvian, subtemporal, and transcortical (trans-middle temporal gyrus) selective amygdalohippocampectomy 6).

The ATL group scored significantly worse for recognition of fear compared with selective amygdalohippocampectomy (SAH) patients. Inversely, after SAH scores for disgust were significantly lower than after ATL, independently of the side of resection. Unilateral temporal damage impairs facial emotion recognition (FER). Different neurosurgical procedures may affect FER differently 7).

Outcome

Functional MRIResting state fMRIdiffusion tensor imaging modalities can be used effectively, in an additive fashion, to predict functional reorganization and cognitive outcome following anterior temporal lobectomy 8).

Complications

Case series

Of 1214 patients evaluated for surgery in the epilepsy Center of Faculdade de Medicina de São Jose do Rio Preto (FAMERP), a tertiary Brazilian epilepsy center, 400 underwent ATL for MTS. Number and type of auras was analyzed and compared with Engel Epilepsy Surgery Outcome Scalefor outcome.

Analyzing the patients by the type of aura, those who had extratemporal auras had worst result in post-surgical in Engel classifcation. While mesial auras apparently is a good prognostic factor. Patients without aura also had worse prognosis. Simple and multiple aura had no difference. In order to identify the most appropriate candidates for ATL, is very important to consider the prognostic factors associated with favorable for counseling patients in daily practice 9).


Boucher et al. compared preoperative vs. postoperative memory performance in 13 patients with selective amygdalohippocampectomy (SAH) with 26 patients who underwent ATL matched on side of surgery, IQ, age at seizure onset, and age at surgery. Memory function was assessed using the Logical Memory subtest from the Wechsler Memory Scales – 3rd edition (LM-WMS), the Rey Auditory Verbal Learning Test (RAVLT), the Digit Span subtest from the Wechsler Adult Intelligence Scale, and the Rey-Osterrieth Complex Figure Test. Repeated measures analyses of variance revealed opposite effects of SAH and ATL on the two verbal learning memory tests. On the immediate recall trial of the LM-WMS, performance deteriorated after ATL in comparison with that after SAH. By contrast, on the delayed recognition trial of the RAVLT, performance deteriorated after SAH compared with that after ATL. However, additional analyses revealed that the latter finding was only observed when surgery was conducted in the right hemisphere. No interaction effects were found on other memory outcomes. The results are congruent with the view that tasks involving rich semantic content and syntactical structure are more sensitive to the effects of lateral temporal cortex resection as compared with mesiotemporal resection. The findings highlight the importance of task selection in the assessment of memory in patients undergoing TLE surgery10).

References

1)

Busby N, Halai AD, Parker GJM, Coope DJ, Lambon Ralph MA. Mapping whole brain connectivity changes: The potential impact of different surgical resection approaches for temporal lobe epilepsy. Cortex. 2018 Nov 17;113:1-14. doi: 10.1016/j.cortex.2018.11.003. [Epub ahead of print] PubMed PMID: 30557759.
2) , 5)

Wiebe S, Blume WT, Girvin JP, Eliasziw M. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001;345(5):311–318.
3)

PENFIELD W, BALDWIN M. Temporal lobe seizures and the technic of subtotal temporal lobectomy. Ann Surg. 1952 Oct;136(4):625-34. PubMed PMID: 12986645; PubMed Central PMCID: PMC1803045.
4)

Schaller K, Cabrilo I. Anterior temporal lobectomy. Acta Neurochir (Wien). 2016 Jan;158(1):161-6. doi: 10.1007/s00701-015-2640-0. Epub 2015 Nov 23. PubMed PMID: 26596998.
6)

Wheatley BM. Selective amygdalohippocampectomy: the trans-middle temporal gyrus approach. Neurosurg Focus. 2008 Sep;25(3):E4. doi: 10.3171/FOC/2008/25/9/E4. Review. PubMed PMID: 18759628.
7)

Wendling AS, Steinhoff BJ, Bodin F, Staack AM, Zentner J, Scholly J, Valenti MP, Schulze-Bonhage A, Hirsch E. Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesiotemporal lobe epilepsy and unilateral hippocampal sclerosis: post-operative facial emotion recognition abilities. Epilepsy Res. 2015 Mar;111:26-32. doi: 10.1016/j.eplepsyres.2015.01.002. Epub 2015 Jan 16. PubMed PMID: 25769370.
8)

Osipowicz K, Sperling MR, Sharan AD, Tracy JI. Functional MRI, resting state fMRI, and DTI for predicting verbal fluency outcome following resective surgery for temporal lobe epilepsy. J Neurosurg. 2016 Apr;124(4):929-37. doi: 10.3171/2014.9.JNS131422. Epub 2015 Sep 25. PubMed PMID: 26406797.
9)

da Cruz Adry RAR, Meguins LC, Pereira CU, da Silva Júnior SC, de Araújo Filho GM, Marques LHN. Auras as a prognostic factor in anterior temporal lobe resections for mesial temporal sclerosis. Eur J Neurol. 2018 Jun 28. doi: 10.1111/ene.13740. [Epub ahead of print] PubMed PMID: 29953714.
10)

Boucher O, Dagenais E, Bouthillier A, Nguyen DK, Rouleau I. Different effects of anterior temporal lobectomy and selective amygdalohippocampectomy on verbal memory performance of patients with epilepsy. Epilepsy Behav. 2015 Oct 12;52(Pt A):230-235. doi: 10.1016/j.yebeh.2015.09.012. [Epub ahead of print] PubMed PMID: 26469799.

Pediatric Chiari type 1 deformity

Epidemiology

Chiari type 1 deformity is commonly seen in pediatric neurology, neuroradiology, and neurosurgery and may have various clinical presentations depending on patient age. In addition, Chiari type 1 deformity is increasingly found by neuroimaging studies as an incidental finding in asymptomatic children 1).

Treatment

The ideal management in children regarding surgical and radiographic decision making is not clearly delineated.

Entezami et al., from the Department of Neurosurgery, AlbanyThomas Jefferson University, , Brown University, Providence, retrospectively reviewed a cohort of patients age 18 years and younger referred to a single neurosurgeon for CM1. Baseline MRIs of the spine were obtained. Non-operative patients had repeat imaging at 6-12 months. Patients who underwent an operation (decompression with/without duraplasty) had repeat imaging at 6 months.

One hundred and thirty-two patients with mean age of 10 years met inclusion criteria. All patients had post-operative symptomatic improvement.

They identified 26 patients with syrinx, 8 with scoliosis, 3 with hydrocephalus, and one had tethered cord. The average tonsillar descent was 8.1 mm in the non-operative group and 11.9 mm in the operative group. Ninety-five patients were managed conservatively (72%). Thirty-seven were offered surgery (28%), and 33 patients underwent intervention; 21 with duraplasty (64%) and 12 without (36%).

Pediatric patients with CM1 require both clinical and radiographic follow-up. Duraplasty may be performed if decompression fails to relieve symptomatology, but is not always needed. CM1 continues to present a challenge in surgical decision making. Adhering to a treatment paradigm may help alleviate difficult decision-making 2).

Chiari malformation Type I (CM-I) related to syndromic craniosynostosis in pediatric patients has been well-studied. The surgical management consists of cranial vault remodeling with or without posterior fossa decompression.

Outcome

Efforts to guide preoperative counseling and improve outcomes research are impeded by reliance on small, single-center studies.

Approximately 1 in 8 pediatric CM-I patients experienced a surgical complication, whereas medical complications were rare. Although complex chronic conditions (CCC) were common in pediatric CM-I patients, only hydrocephalus was independently associated with increased risk of surgical events. These results may inform patient counseling and guide future research efforts 3).

CM-I in children is not a radiologically static entity but rather is a dynamic one. Radiological changes were seen throughout the 7 years of follow-up. A reduction in tonsillar herniation was substantially more common than an increase. Radiological changes did not correlate with neurological examination finding changes, symptom development, or the need for future surgery. Follow-up imaging of asymptomatic children with CM-I did not alter treatment for any patient. It would be reasonable to follow these children with clinical examinations but without regular surveillance MRI 4).

Outcome assessment for the management of Chiari malformation type 1 is difficult because of the lack of a reliable and specific surgical outcome assessment scale. Such a scale could reliably correlate postoperative outcomes with preoperative symptoms.

Outcome is poor in approximately 3 in 10 patients 5).

The degree of tonsillar herniation has not been a reliable predictor of either symptom severity 6) or surgical outcome 7).

Arnautovic et al. identified 145 operative series of patients with CM-I, primarily from the United States and Europe, and divided patient ages into 1 of 3 categories: adult (> 18 years of age; 27% of the cases), pediatric (≤ 18 years of age; 30%), or unknown (43%). Most series (76%) were published in the previous 21 years. The median number of patients in the series was 31. The mean duration of the studies was 10 years, and the mean follow-up time was 43 months. The peak ages of presentation in the pediatric studies were 8 years, followed by 9 years, and in the adult series, 41 years, followed by 46 years. The incidence of syringomyelia was 65%. Most of the studies (99%) reported the use of posterior fossa/foramen magnum decompression. In 92%, the dura was opened, and in 65% of these cases, the arachnoid was opened and dissected; tonsillar resection was performed in 27% of these patients. Postoperatively, syringomyelia improved or resolved in 78% of the patients. Most series (80%) reported postoperative neurological outcomes as follows: 75% improved, 17% showed no change, and 9% experienced worsening. Postoperative headaches improved or resolved in 81% of the patients, with a statistical difference in favor of the pediatric series. Postoperative complications were reported for 41% of the series, most commonly with CSF leak, pseudomeningocele, aseptic meningitis, wound infection, meningitis, and neurological deficit, with a mean complication rate of 4.5%. Complications were reported for 37% of pediatric, 20% of adult, and 43% of combined series. Mortality was reported for 11% of the series. No difference in mortality rates was seen between the pediatric and adult series 8).

Case reports

A 16-year-old boy who admitted with symptoms related to CM-I. With careful examination and further genetic investigations, a diagnosis of Crouzon syndrome was made, of which the patient and his family was unaware before. The patient underwent surgery for posterior fossa decompression and followed-up for Crouzon’s syndrome.

This is the only case report indicating a late adolescent diagnosis of Crouzon syndrome through clinical symptoms of an associated CM-I 9).

References

1)

Poretti A, Ashmawy R, Garzon-Muvdi T, Jallo GI, Huisman TA, Raybaud C. Chiari Type 1 Deformity in Children: Pathogenetic, Clinical, Neuroimaging, and Management Aspects. Neuropediatrics. 2016 Jun 23. [Epub ahead of print] PubMed PMID: 27337547.
2)

Entezami P, Gooch MR, Poggi J, Perloff E, Dupin M, Adamo MA. Current management of pediatric chiari type 1 malformations. Clin Neurol Neurosurg. 2018 Dec 10;176:122-126. doi: 10.1016/j.clineuro.2018.12.007. [Epub ahead of print] PubMed PMID: 30557765.
3)

Greenberg JK, Olsen MA, Yarbrough CK, Ladner TR, Shannon CN, Piccirillo JF, Anderson RC, Wellons JC 3rd, Smyth MD, Park TS, Limbrick DD Jr. Chiari malformation Type I surgery in pediatric patients. Part 2: complications and the influence of comorbid disease in California, Florida, and New York. J Neurosurg Pediatr. 2016 May;17(5):525-32. doi: 10.3171/2015.10.PEDS15369. Epub 2016 Jan 22. PubMed PMID: 26799408.
4)

Whitson WJ, Lane JR, Bauer DF, Durham SR. A prospective natural history study of nonoperatively managed Chiari I malformation: does follow-up MRI surveillance alter surgical decision making? J Neurosurg Pediatr. 2015 Aug;16(2):159-66. doi: 10.3171/2014.12.PEDS14301. Epub 2015 May 1. PubMed PMID: 25932776.
5)

Aliaga L, Hekman KE, Yassari R, Straus D, Luther G, Chen J, Sampat A, Frim D. A novel scoring system for assessing Chiari malformation type I treatment outcomes. Neurosurgery. 2012 Mar;70(3):656-64; discussion 664-5. doi: 10.1227/NEU.0b013e31823200a6. PubMed PMID: 21849925.
6)

Khan AA, Bhatti SN, Khan G, et al. Clinical and radiological findings in Arnold Chiari malformation. J Ayub Med Coll Abbottabad. 2010;22(2):75-78.
7)

NoudelR,GomisP,SotoaresG,etal.Posteriorfossavolumeincreaseaftersurgery for Chiari malformation type I: a quantitative assessment using magnetic resonance imaging and correlations with the treatment response. J Neurosurg. 2011;115(3): 647-658.
8)

Arnautovic A, Splavski B, Boop FA, Arnautovic KI. Pediatric and adult Chiari malformation Type I surgical series 1965-2013: a review of demographics, operative treatment, and outcomes. J Neurosurg Pediatr. 2015 Feb;15(2):161-77. doi: 10.3171/2014.10.PEDS14295. Epub 2014 Dec 5. PubMed PMID: 25479580.
9)

Canpolat A, Akçakaya MO, Altunrende E, Ozlü HM, Duman H, Ton T, Akdemir O. Chiari Type I malformation yielded to the diagnosis of Crouzon syndrome. J Neurosci Rural Pract. 2014 Jan;5(1):81-3. doi: 10.4103/0976-3147.127885. PubMed PMID: 24741262.

Rating

A rating is the evaluation or assessment of something, in terms of quality (as with a critic rating a novel), quantity (as with an athlete being rated by his or her statistics), or some combination of both.

Patient satisfaction ratings are increasingly used for hospital rankings, referral base and physician reimbursement. As such, online physician rating websites (PRWs) are quickly becoming a topic of interest.


Hopkins et al., analyzed physician reported industry payments received by neurosurgeons over four consecutive years as defined by the Physician Payments Sunshine Act (PPSA). All board-certified neurosurgeons on three widely used Physician Rating Websites (PRWs).

Data was collected on average rating, number of ratings and composite ratings. Demographics, training-related and practice-related data were also collected. Each physician was identified and matched to their individually reported payments from the PPSA database.

Receiving higher amounts of industrial payments had no correlation to average PRW ratings, however was associated with receiving higher composite PRW ratings (p = 0.0389). Higher composite ratings (p = 0.0389), decreasing age (p = 0.005), being male (OR 1.7960, p = 0.005), completing a fellowship (OR 1.3310, p = 0.0085), having a more complete profile (OR 1.1121, p = 0.0057) and speaking more languages (OR 1.1253, p = 0.03802) all were correlated with receiving more total monetary payments. Training at a top 25 residency program was predictive of being in the bottom quartile of total monetary payments received (OR 1.676, p = 0.0002).

Patient experience as defined by PRW ratings are likely not strongly influenced by industry related monetary payments, however some relationship may exist. Further study is needed to determine the true relationship between industry related monetary payments and the patient experience 1).

1)

Hopkins B, Yamaguchi JT, Cloney MB, Shlobin NA, Dahdaleh NS. Effects of the physician payments sunshine act on the patient experience and perception of care amongst neurosurgeons: A comparative study of online PRW ratings and industry payments. Clin Neurol Neurosurg. 2018 Dec 11;176:127-132. doi: 10.1016/j.clineuro.2018.12.008. [Epub ahead of print] PubMed PMID: 30557766.

Hemopatch®

http://www.hemopatch.com/

Nowak et al., from Greifswald, analyzed the results using Hemopatch® as a new dural sealant after durotomy in cranial and spinal neurosurgical procedures.

In this prospective single center study, they analyzed all patients who received Hemopatch® used as a dural sealant between October 2016 and May 2017. 34 patients received Hemopatch® used as a dural sealant in the study period. They included 23 (67.6%) female and 11 (32.3%) male patients. The mean age was 56 years (4-83 years). They included emergency and elective surgical procedures as well as spinal and cranial intradural surgery. They did not exclude any type of underlying pathology. They took note of the general patient data, the size of Hemopatch® used, the type of dural closure, and the postoperative stay. Additionally, they recorded the type of dural closure (watertight/ watertight with additional muscle patch/ not watertight with small or large defect (>1 cm) remaining) and of preoperative hydrocephalus as well as intraoperative ventricular opening.

Hemopatch® was used in addition to the following dural closures: 11 (32.4%) watertight suture, 23 (67.6%) non-watertight suture. Three (8.8%) surgeries were emergency procedures. The site of surgery was as follows: 18 (52.9%) supratentorial, 16 (47.1%) infratentorial. A ventricular opening was performed in 13 (38.2%) cases. A hydrocephalus was present in 2 (5.9%) cases. A revision surgery after use of Hemopatch® was performed in 2 (5.9%) patients. Postoperative CSF fistulas and infections were observed in 2 patients each.

They could demonstrate the safety and efficiency of Hemopatch® used as dural sealant after durotomy in microneurosurgical procedures. To confirm our promising results a larger prospective randomized controlled trial will be needed 1)


Cerebrospinal fluid leakage occurs in 4% to 32% of cranial surgeries and is associated with significant patient burden and expense. The use of sealant as an adjunct to primary dural closure is assumed to help prevent CSF leakage.

van Doormaal et al., evaluated 9 commonly used dural sealants, including Tachosil (Takeda Inc, Osaka, Japan), Adherus (Hyperbranch Inc, Durham, North Carolina), Duraform (Codman, Raynham, Massachusetts), Tissudura (Baxter, Deerfield, Illinois), Hemopatch (Baxter), TissuePatchDural (Tissuemed, Leeds, United Kingdom), Tisseel (Baxter), Duragen Secure (Integra, Plainsboro, New Jersey), and Duraseal, (Integra). Sealants were tested in 2 novel in Vitro setups using fresh porcine dura: the first tested the acute burst pressure of a sealed 3-mm gap, while the second examined resistance to a pressure wave mimicking intracranial pressure for 72 h.

Adherus showed the highest mean burst pressure (87 ± 47 mmHg) followed by Tachosil (71 ± 16 mmHg) and Duraseal (51 ± 42 mmHg); these were the only 3 sealants showing burst pressures above normal physiological intracranial pressure. In the 72-h setup, only Adherus and Duraseal maintained appropriate sealing for the duration of the experiment. Tachosil released from the dura after 1.4 h (95% confidence interval, -1.8-4.7).

Given the high cost of sealants and the results of this study, they advocate a critical attitude toward sealant application as an adjunct to classic dural closure 2).

References

 
1)
Nowak S, Schroeder HWS, Fleck S. Hemopatch(®) as a new dural sealant: A clinical observation. Clin Neurol Neurosurg. 2018 Dec 11;176:133-137. doi: 10.1016/j.clineuro.2018.12.009. [Epub ahead of print] PubMed PMID: 30557767.
2)
van Doormaal T, Kinaci A, van Thoor S, Redegeld S, Bergmann W, van der Zwan A. Usefulness of Sealants for Dural Closure: Evaluation in an In Vitro Model. Oper Neurosurg (Hagerstown). 2018 Oct 1;15(4):425-432. doi: 10.1093/ons/opx260. PubMed PMID: 29281065.

Anaplastic pleomorphic xanthoastrocytoma

Anaplastic pleomorphic xanthoastrocytoma (PXA) is a newly recognized entity in the World Health Organization Classification of Tumors of the Central Nervous System 2016, characterized by elevated mitotic activity with or without necrosis, and shorter survival when compared with WHO grade II PXAs. BRAF V600E mutations are frequent.

Treatment

While grade II PXAs can often be managed surgically, there is no consensus on the optimal treatment for anaplastic PXA. Rarely, anaplastic PXA can present with leptomeningeal dissemination (LMD), which is associated with poor prognosis.

Case reports

In a report Purkait et al., from the All India Institute of Medical Sciences, Bhubaneswar, India.describe a BRAF V600E-mutated tumor with divergent morphological appearance comprising of anaplastic pleomorphic xanthoastrocytoma and astroblastoma. Both of these tumor entities are extremely rare and a combined morphology has not been described till now 1).


A 16-year-old girl diagnosed with a left frontal anaplastic PXA with BRAF V600E mutations and high grade features of necrosis. Following subtotal resection, cranial radiation, and temozolomide chemotherapy her tumor recurred with bulky, nodular LMD throughout the cervical, thoracic, and lumbar spine. She received palliative radiation to the thoracic spine and then started targeted therapy with dabrafenib with a partial radiographic response and then trametinib was added to dabrafenib with sustained response for 5 months. When the leptomeningeal tumor progressed, bevacizumab was added to the dabrafenib and trametinib therapy, and the patient remained stable for an additional 4 months. The combined therapy was very well tolerated; the patient experienced a grade II rash with initiation of dabrafenib, but no other side effects. To our knowledge this is the first time dabrafenib, trametinib, and bevacizumab have been combined to treat a pediatric high grade glioma. This is also the first report of BRAF inhibition in glial LMD. Our experience suggests that targeted therapy with dabrafenib and trametinib can be safely combined with anti-angiogenic therapy and may improve quality of life and survival in patients with LMD associated with high grade PXA. The growing experience with targeted therapy in rare pediatric gliomas may justify a need for a larger clinical trial 2). 1) Purkait S, Bansal S, Malgulwar PB. BRAF V600E-mutated central nervous system tumor with divergent morphological feature – Anaplastic pleomorphic xanthoastrocytoma-like and astroblastoma-like. Neuropathology. 2018 Dec 17. doi: 10.1111/neup.12527. [Epub ahead of print] PubMed PMID: 30557911. 2)https://academic.oup.com/neuro-oncology/article-abstract/19/suppl_6/vi216/4591299?redirectedFrom=fulltext

5 aminolevulinic acid fluorescence guided resection

Indications

5-ALA-based fluorescence guided surgery has been shown to be a safe and effective method to improve intraoperative visualization and resection of malignant gliomas. However, it remains ineffective in guiding the resection of lower-grade, non-enhancing, and deep-seated tumors, mainly because these tumors do not produce detectable fluorescence with conventional visualization technologies, namely, wide-field (WF) surgical microscope. The introduction of fluorescence guided resection (FGS) represents one of the most important advances in the neurosurgical treatment of brain tumors.

5 aminolevulinic acid fluorescence guided resection permits the intraoperative visualization of malignant glioma tissue and supports the neurosurgeon with real-time guidance for differentiating tumor from normal brain that is independent of neuronavigation and brain shift.

Wei et al., describe some of the main factors that limit the sensitivity and accuracy of conventional WF surgical microscopy, and then provide a survey of commercial and research prototypes being developed to address these challenges, along with their principles, advantages and disadvantages, as well as the current status of clinical translation for each technology. They also provide a neurosurgical perspective on how these visualization technologies might best be implemented for guiding glioma surgeries in the future

Detection of PpIX expression in low-grade gliomas and at the infiltrative margins of all gliomas has been achieved with high-sensitivity probe-based visualization techniques. Deep-tissue PpIX imaging of up to 5 mm has also been achieved using red-light illumination techniques. Spectroscopic approaches have enabled more accurate quantification of PpIX expression.

Advancements in visualization technologies have extended the sensitivity and accuracy of conventional WF surgical microscopy. These technologies will continue to be refined to further improve the extent of resection in glioma patients using 5-ALA-induced fluorescence 1).

The 5 aminolevulinic acid has been used in glioma surgery and recent studies applied in Sylvian and spinal meningiomas 2) 3).

see 5 aminolevulinic acid fluorescence guided resection of glioma

see 5 aminolevulinic acid fluorescence guided resection of intracranial meningioma

see 5 aminolevulinic acid fluorescence guided resection in children

see 5 aminolevulinic acid fluorescence guided resection and intraoperative monitoring

see 5 aminolevulinic acid fluorescence guided resection of high grade glioma.

see 5 aminolevulinic acid fluorescence guided resection of low grade glioma.

Meningeal sarcoma

First case published in the literature of meningeal sarcoma in a child in which intraoperative fluorescence with 5-ALA was used to achieve a complete resection 4).

Meningioma

Metabolic imaging tools such as 5-ALA fluorescence-guided resection and navigated FET-PET were helpful for the resection of complex-shaped, recurrent skull base meningioma. 5-ALA fluorescence was useful to dissect the adherent interface between tumor and brain. Furthermore, it helped to delineate tumor margins in the nasal cavity. FET-PET improved the assessment of bony and dural infiltration. We hypothesize that these imaging technologies may reduce recurrence rates through better visualization of tumor tissue that might be left unintentionally. This has to be verified in larger, prospective trials 5).

Tumor fluorescence can occur in benign meningiomas (WHO grade I) as well as in WHO grade II and WHO grade III meningiomas. Most of the reviewed studies report fluorescence of the main tumor mass with high sensitivity and specificity. However, different parts of the same tumor can present with a different fluorescent pattern (heterogenic fluorescence). Quantitative probe fluorescence can be superior, especially in meningiomas with difficult anatomical accessibility. However, only one study was able to consistently correlate resected tissue with histopathological results and nonspecific fluorescence of healthy brain tissue remains a confounder. The use of 5-ALA as a tool to guide resection of intracranial meningiomas remains experimental, especially in cases with tumor recurrence. The principle of intraoperative fluorescence as a real-time method to achieve complete resection is appealing, but the usefulness of 5-ALA is questionable. 5-ALA in intracranial meningioma surgery should only be used in a protocolled prospective and long-term study 6).

Spinal tumor

The application of 5-ALA has also been described in spinal tumors.

Three hours before the induction of anesthesia, 5-ALA was administered to patients with different intra- and extradural spinal tumors. In all patients a neurosurgical resection or biopsy of the spinal tumor was performed under conventional white-light microscopy. During each surgery, the presence of Protoporphyrin IX fluorescence was additionally assessed using a modified neurosurgical microscope. At the end of an assumed gross-total resection (GTR) under white-light microscopy, a final inspection of the surgical cavity of fluorescing intramedullary tumors was performed to look for any remaining fluorescing foci. Histopathological tumor diagnosis was established according to the current WHO classification.

Fifty-two patients with 55 spinal tumors were included in this study. Resection was performed in 50 of 55 cases, whereas 5 of 55 cases underwent biopsy. Gross-total resection was achieved in 37 cases, STR in 5, and partial resection in 8 cases. Protoporphyrin IX fluorescence was visible in 30 (55%) of 55 cases, but not in 25 (45%) of 55 cases. Positive PpIX fluorescence was mainly detected in ependymomas (12 of 12), meningiomas (12 of 12), hemangiopericytomas (3 of 3), and in drop metastases of primary CNS tumors (2 of 2). In contrast, none of the neurinomas (8 of 8), carcinoma metastases (5 of 5), and primary spinal gliomas (3 of 3; 1 pilocytic astrocytoma, 1 WHO Grade II astrocytoma, 1 WHO Grade III anaplastic oligoastrocytoma) revealed PpIX fluorescence. It is notable that residual fluorescing tumor foci were detected and subsequently resected in 4 of 8 intramedullary ependymomas despite assumed GTR under white-light microscopy.

In this study, 5-ALA-PpIX fluorescence was observed in spinal tumors, especially ependymomas, meningiomas, hemangiopericytomas, and drop metastases of primary CNS tumors. In cases of intramedullary tumors, 5-ALA-induced PpIX fluorescence is a useful tool for the detection of potential residual tumor foci 7).

Complications

Stummer et al. showed that 5–ALA guided resections carry a higher risk of post-operative neurological deterioration than conventional resections (26% vs 15%, respectively), even though the difference vanished within weeks 8).

Just as tumour tissue is often indiscernible from normal brain tissue, functionally critical tissues are indistinguishable from tissues with less clinically relevant functions.

Thus, knowing when to stop a resection due to proximity to areas of crucial neurological functions is of obvious and utmost importance. Detailed knowledge of the normal brain anatomy and distribution of function is not sufficient during glioma resection. Interindividual variability and functional relocation (i.e., plasticity) induced by the presence of an infiltrating tumour 9) requires an exact functional brain map at the site of surgery in order to spare areas involved in crucial (so-called eloquent) functions. Preoperative localisation of function, either with functional MRI (fMRI) or navigated transcranial magnetic stimulation (nTMS), provides an approximate map 10) 11).

Furthermore, intra-operative direct cortical and subcortical electrical stimulation (DCS) for functional analysis of the tissue in the tumour’s infiltration zone is required for accurate identification of areas that need to be spared in order to retain the patient’s functional integrity 12) 13). Motor evoked potentials (MEP) provide real-time information on the integrity of the primary motor cortex and the corticospinal tract 14). Direct cortical mapping and phase reversal identify the primary motor and sensory cortices. Subcortical mapping can estimate the distance to the pyramidal tract, acting as guidance close to functionally critical areas 15). When integrated into the existing surgical tools, continuous and dynamic mapping enables more extensive resection while simultaneously protecting motor function 16). Using these techniques and a detailed electrophysiological “Bern-concept”, a group achieved complete motor function protection in 96% of patients with high-risk motor eloquent tumours 17). Furthermore, localisation of cortical and subcortical regions relevant to language function is essential for speech preservation during resection of gliomas in proximity to presumed speech areas 18) and requires the patient to be awake during the brain mapping part of surgery. Similarly, intra-operative mapping of visual functions may contribute to increased resections while avoiding tissue essential for vision within the temporal and occipital lobes 19).

References

1) Wei L, Roberts DW, Sanai N, Liu JTC. Visualization technologies for 5-ALA-based fluorescence-guided surgeries. J Neurooncol. 2018 Dec 15. doi: 10.1007/s11060-018-03077-9. [Epub ahead of print] Review. PubMed PMID: 30554344.2) Chae MP, Song SW, Park SH, Park CK. Experience with 5- aminolevulinic Acid in fluorescence-guided resection of a deep sylvian meningioma. J Korean Neurosurg Soc. 2012;52:558–60.3) Stummer W, Novotny A, Stepp H, Goetz C, Bise K, Reulen HJ. Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: A prospective study in 52 consecutive patients. J Neurosurg. 2000;93:1003–13.4) Bernal García LM, Cabezudo Artero JM, Royano Sánchez M, Marcelo Zamorano MB, López Macías M. Fluorescence-guided resection with 5-aminolevulinic acid of meningeal sarcoma in a child. Childs Nerv Syst. 2015 Apr 12. [Epub ahead of print] PubMed PMID: 25863951.5) Cornelius JF, Slotty PJ, Stoffels G, Galldiks N, Langen KJ, Steiger HJ. 5-Aminolevulinic Acid and (18)F-FET-PET as Metabolic Imaging Tools for Surgery of a Recurrent Skull Base Meningioma. J Neurol Surg B Skull Base. 2013 Aug;74(4):211-6. doi: 10.1055/s-0033-1342918. Epub 2013 Apr 1. PubMed PMID: 24436914.6) Motekallemi A, Jeltema HR, Metzemaekers JD, van Dam GM, Crane LM, Groen RJ. The current status of 5-ALA fluorescence-guided resection of intracranial meningiomas-a critical review. Neurosurg Rev. 2015 Mar 5. [Epub ahead of print] PubMed PMID: 25736455.7) Millesi M, Kiesel B, Woehrer A, Hainfellner JA, Novak K, Martínez-Moreno M, Wolfsberger S, Knosp E, Widhalm G. Analysis of 5-aminolevulinic acid-induced fluorescence in 55 different spinal tumors. Neurosurg Focus. 2014 Feb;36(2):E11. doi: 10.3171/2013.12.FOCUS13485. PubMed PMID: 24484249.8) Stummer W1, Tonn JC, Mehdorn HM, Nestler U, Franz K, Goetz C, et al. ALA-Glioma Study Group. Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5–aminolevulinic acid glioma resection study. J Neurosurg. 2011;114(3):613–23. doi: 10.3171/2010.39) Ojemann G, Ojemann J, Lettich E, Berger M. Cortical language localization in left, dominant hemisphere. An electrical stimulation mapping investigation in 117 patients. J Neurosurg. 1989;71(3):316–26.10) Seghier ML, Lazeyras F, Pegna AJ, Annoni JM, Zimine I, Mayer E, et al. Variability of fMRI activation during a phonological and semantic language task in healthy subjects. Hum Brain Mapp. 2004;23(3):140–55.11) Krieg SM, Shiban E, Buchmann N, Gempt J, Foerschler A, Meyer B, et al. Utility of presurgical navigated transcranial magnetic brain stimulation for the resection of tumors in eloquent motor areas. J Neurosurg. 2012;116(5):994–1001. doi: 10.3171/2011.12.JNS11152412) , 18) Duffau H, Capelle L, Sichez N, Denvil D, Lopes M, Sichez JP, et al. Intraoperative mapping of the subcortical language pathways using direct stimulations. An anatomo-functional study. Brain. 2002;125(1):199–214.13) Duffau H, Capelle L, Denvil D, Sichez N, Gatignol P, Taillandier L, et al. Usefulness of intraoperative electrical subcortical mapping during surgery for low-grade gliomas located within eloquent brain regions: functional results in a consecutive series of 103 patients. J Neurosurg. 2003;98(4):764–78.14) Seidel K, Beck J, Stieglitz L, Schucht P, Raabe A. The warning-sign hierarchy between quantitative subcortical motor mapping and continuous motor evoked potential monitoring during resection of supratentorial brain tumors. J Neurosurg. 2013;118(2):287–96.15) Seidel K, Beck J, Stieglitz L, Schucht P, Raabe A. Low Threshold Monopolar Motor Mapping for Resection of Primary Motor Cortex Tumors. Neurosurgery. 2012;71(1):104–14.16) Raabe A, Beck J, Schucht P, Seidel K. Continuous dynamic mapping of the corticospinal tract during surgery of motor eloquent brain tumors: evaluation of a new method. J Neurosurg. 2014;120(5)1015–24. doi: 10.3171/2014.1.JNS13909.17) Schucht P, Seidel K. Beck J, Murek M, Jilch A, Wiest R, et al. Intraoperative monopolar mapping during 5-ALA-guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome. Neurosurg Focus. 2014;27(6):E16.19) Gras-Combe G, Moritz-Gasser S, Herbet G, Duffau H. Intraoperative subcortical electrical mapping of optic radiations in awake surgery for glioma involving visual pathways. J Neurosurg. 2012;117(3):466–73.

Gut flora

The gastrointestinal tract contains thousands of different bacteria in their gut flora.

The gut microbiota has recently gained attention as a possible modulator of brain activity. A number of reports suggest that the microbiota may be associated with neuropsychiatric conditions such as major depressive disorder, autism, and anxiety. The gut microbiota is thought to influence the brain via vagus nerve signaling, among other possible mechanisms. The insula processes and integrates these vagal signals. To determine if microbiota diversity and structure modulate brain activity.

Curtis et al., collected fecal samples and examined insular function using resting state functional connectivity (RSFC). Thirty healthy participants (non-smokers, tobacco smokers, and electronic cigarette users, n=10 each) were studied.

They found that the RSFC between the insula and several regions (frontal pole left, lateral occipital cortex right, lingual gyrus right, and cerebellum and vermis) were associated with bacterial microbiota diversity and structure. In addition, two specific bacteria genera, Prevotella and Bacteroides, were specifically different in tobacco smokers and also associated with insular connectivity. In conclusion, they showed that insular connectivity is associated with microbiome diversity, structure, and at least two specific bateria genera. Furthemore, this association is potentially modulated by tobacco smoking, although the sample sizes for the different smoking groups were small and this result needs validation in a larger cohort. While replication is necessary, the microbiota is a readily accesible therapeutic target for modulating insular connectivity, which has previously been shown to be abnormal in anxiety and tobacco use disorders 1).

References

1) Curtis K, Stewart CJ, Robinson M, Molfese DL, Gosnell SN, Kosten TR, PetrosinoJF, De La Garza R II, Salas R. Insular Resting State Functional Connectivity is Associated with Gut Microbiota Diversity. Eur J Neurosci. 2018 Dec 16. doi:10.1111/ejn.14305. [Epub ahead of print] PubMed PMID: 30554441.

Loin Pain Hematuria Syndrome

Loin Pain Hematuria Syndrome (LPHS) is a rare condition characterized by cryptogenic debilitating flank pain and microscopic or macroscopic hematuria.

Pathophysiology

The pathophysiology of LPHS remains poorly understood and diagnosis is made largely by exclusion of alternate pathology.

Treatment

Management strategies can vary widely and include chronic opioid medication and a variety of invasive procedures including regional nerve blocks, transcutaneous electrical nerve stimulation, local capsaicin infusion, and surgical renal denervation. Neuromodulation may provide a new paradigm of treatment for LPHS, potentially sparing patients from long term complications of opiate therapy and invasive surgery.

A report of Richter et al. from the Department of Neurosurgery, Allegheny General Hospital, demonstrates the first case of successful symptomatic management of LPHS using spinal cord stimulation1).

1) Richter B, Bergman J, Pierre J, Tomycz ND. Spinal Cord Stimulation for LoinPain Hematuria Syndrome: Case Report. Pain Pract. 2018 Dec 16. doi:10.1111/papr.12755. [Epub ahead of print] PubMed PMID: 30554461.

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