Advances in Pain Medicine – International Winter Symposium

The London Pain Forum “Advances in Pain Medicine” International Winter Symposium will be returning to the Hotel Village Montana, Tignes Le Lac, France on 20-25 January 2019 with a six day programme of lectures and expert discussions.

Programme

More Information


PAIN MANAGEMENT MEETINGS 

7th London Pain Forum “Advances in Pain Medicine” Winter Symposium
20-25 January 2019
Hotel Village Montana, Tignes Le Lac, France
Web: www.winterpainsymposium.com

12th RA-UK/ESRA/LPF Ultrasound in Chronic Pain Medicine Course
22-23 March 2019
Dept of Anatomy, St George’s Hospital, London, U
Web: www.uspmlondon.com

Headache and Facial Pain Treatment Symposium
5 April 2019
Park Plaza Victoria, Amsterdam Centraal, The Netherlands
Web: www.painways.com

British Pain Society Annual Scientific Meeting
1-3 May 2019
Hilton Tower Bridge Hotel, London, UK
Web: www.britishpainsociety.org


12th Annual Leeds Hands-on Interventional Workshop
9-10 May 2019
University of Leeds, Leeds, UK
Web: www.painandneuromodulationlondon.com

6th SUA Ultrasound Guided Chronic Pain Interventions Workshop
3 September 2019
Royal College of Physicians, London, UK
Web: www.painandneuromodulationlondon.com

Neuromodulation Society of the UK & Ireland Annual Scientific Meeting
and Hands-on Cadaver Workshop
15-17 November 2019
Aspire Conference Centre & Dept of Anatomy, Univ. of Leeds, Leeds, UK
Web: www.painandneuromodulationlondon.com

Hypernatremia

Hypernatremia

Hypernatremia, is a high concentration of sodium in the blood. Normal serum sodium levels are 135 – 145 mmol/L (135 – 145 mEq/L). Hypernatremia is generally defined as a serum sodium level of more than 145 mmol/L.

Hypernatremia is one of the most common electrolyte disturbances following aneurysmal subarachnoid hemorrhage (aSAH) and has been correlated with increased mortality in single institution studies. Both hyponatremia and hypernatremia during ICU management were significantly associated with unfavorable neurologic outcomes 1).

In neurosurgical patients, this is most often seen in the setting of diabetes insipidus (DI). Since normal total body water (TBW) is ≈ 60% of the patient’s normal body weight, the patient’s current TBW may be estimated by Eq.

Mild and moderate hypernatremia were significantly associated with increased early mortality in patients with severe TBI 2). Hypernatremia was associated also with poorer outcomes in patients with severe TBI. This finding warrants further investigation in a prospective, randomized study 3).

Electrolyte imbalances are common in traumatic brain injury. In a study Hypokalemia was the most common electrolyte imbalance at 65.5%. The results of the use of a multivariable logistic regression model showed that the odds of postoperative death in TBI patients were increased with high levels of blood glucose, hypernatremia, and acidosis.Hypokalemia was the most common electrolyte imbalance in TBI patients. Hypernatremia, acidosis, and hyperglycemia significantly increased the odds ratio of death in the first 24  hours post TBI 4).

Clinical features

Early symptoms may include a strong feeling of thirstweaknessnausea, and loss of appetite.

Severe symptoms include confusion, muscle twitching, and bleeding in or around the brain.

Severe symptoms typically only occur when levels are above 160 mmol/L.

Treatment

The free water deficit to be replaced is given by a Eq. Correction must be made slowly to avoid exacerbating cerebral edema. One half the water deficit is replaced over 24 hours, and the remainder is given over 1–2 additional days. Judicious replacement of deficient ADH in cases of true DI must also be made.


The aim of a work of Vassilyev was to evaluate the effectiveness of Sterofundin in the framework of complex therapy of hypernatremia in neurosurgical patients after removal of brain tumors. They analyzed the dynamics of the concentrations of sodium, potassium, chorus of the plasma, anion gap and buffer bases in the postoperative period of these patients. For obtaining reliable results, the patients were divided into groups according to the nature of the treatment: Sterofundin and symptomatic correction of hypotonic solution of sodium chloride, saluretic and Spironolactone respectively. In a comparison between the groups, a distinct difference in the speed of regression of hypernatremia and durability of the achieved effect was observed. In case of treatment with Sterofundin there was a significant decrease of hypernatremia by the end of the second day of the postoperative period without tendency to re-raise. The prevalence of hypotonic solutions of sodium chloride and potassium-sparing saluretics in intensive care allowed reducing the sodium concentration non-persistently to the fourth day on the background of significant fluctuations in its concentration. The use of Sterofundin in complex therapy of electrolyte disturbances, particularly of hypernatremia in neurosurgical patients after removal of brain tumors, is reflected in the form of significant regression of increased sodium concentration in plasmacompared with the method of use “hypotonic” hemodilution, saluretics and potassium-sparing diuretics 5).

Complications

Coma.

Pulmonary complications and acute kidney injury were more common in hypernatremia 6).


Hoffman et al., from the Upstate Medical University performed a retrospective analysis of adults between 2002 and 2011 with a primary diagnosis of aneurysmal subarachnoid hemorrhage (aSAH) using the Nationwide Inpatient Sample (NIS). Patients were grouped according to whether or not an inpatient diagnosis of hypernatremia was present. The primary outcome was the NIS-SAH outcome measure. Secondary outcomes included in-hospital mortalitylength of stay (LOS), and non-routine hospital discharge. Outcomes analyses adjusted for SAH severity using the NIS-SAH Severity Score, Charlson Comorbidity Index, and the presence of cerebral edema.

A total of 18,377 patients were included in the study. The incidence of a poor outcome as defined by the NIS-SAH outcome measure was 65.9% in the hypernatremia group and 33.4% in the normonatremia group (OR 1.96, 95% CI 1.68 – 2.27). There was higher mortality in the hypernatremia group (OR 1.60, 95% CI 1.37 – 1.87). Patients with hypernatremia had a significantly higher rate of non-routine hospital discharge and gastrostomy. The incidences of poor outcome, in-hospital mortality, and non-routine disposition were higher in the hypernatremia group regardless of treatment type (clipping vs. endovascular embolization). Pulmonary complications and acute kidney injury were more common in the hypernatremia group as well.

In patients with aSAH, hypernatremia is associated with poorer functional outcomes regardless of SAH severity 7).

References

1)

Okazaki T, Hifumi T, Kawakita K, Shishido H, Ogawa D, Okauchi M, Shindo A, Kawanishi M, Tamiya T, Kuroda Y. Target Serum Sodium Levels During Intensive Care Unit Management of Aneurysmal Subarachnoid Hemorrhage. Shock. 2017 Nov;48(5):558-563. doi: 10.1097/SHK.0000000000000897. PubMed PMID: 28498294.
2)

Vedantam A, Robertson CS, Gopinath SP. Morbidity and mortality associated with hypernatremia in patients with severe traumatic brain injury. Neurosurg Focus. 2017 Nov;43(5):E2. doi: 10.3171/2017.7.FOCUS17418. PubMed PMID: 29088954.
3)

Hoffman H, Jalal MS, Chin LS. Effect of Hypernatremia on Outcomes After severe Traumatic Brain Injury: A Nationwide Inpatient Sample analysis. World Neurosurg. 2018 Oct;118:e880-e886. doi: 10.1016/j.wneu.2018.07.089. Epub 2018 Jul 18. PubMed PMID: 30031178.
4)

Pin-On P, Saringkarinkul A, Punjasawadwong Y, Kacha S, Wilairat D. Serum electrolyte imbalance and prognostic factors of postoperative death in adult traumatic brain injury patients: A prospective cohort study. Medicine (Baltimore). 2018 Nov;97(45):e13081. doi: 10.1097/MD.0000000000013081. PubMed PMID: 30407307; PubMed Central PMCID: PMC6250545.
5)

Vassilyev D. [MODERN APPROACHES TO CORRECTION OF HYPERNATREMIA IN NEUROSURGICAL PATIENTS]. Georgian Med News. 2016 Nov;(Issue):12-16. Russian. PubMed PMID: 28009309.
6) , 7)

Hoffman H, Verhave B, Chin LS. Hypernatremia is associated with poorer outcomes following aneurysmal subarachnoid hemorrhage: a nationwide inpatient sample analysis. J Neurosurg Sci. 2018 Dec 5. doi: 10.23736/S0390-5616.18.04611-8. [Epub ahead of print] PubMed PMID: 30514071.

7th GENEVA SPINE COURSE Sagittal balance Master course

Anatomical workshop
SWISS Foundation for Innovation
and Training in Surgery
Sagittal balance is a complex topic. In order to understand the concepts, a different type of educational course is needed. This course is modeled on a European program, designed by Professor Jean Charles Le Huec, teaching at Bordeaux university medical school and past Eurospine (Spine Society of Europe) president and Dr Antonio Faundez, consultant at Geneva University Hospital.
A comprehensive approach of the balance concept will be presented.
The course is designed to introduce concepts slowly with adequate time for questioning and discussion before moving on to more advanced concepts.
It is mandatory for all participants to visit an e-learning website. You will receive an access code with the payment of your registration. There will be 5 sessions of 10 to 15 min each, which will provide you the basic knowledge that you should have, to be able to actively participate during the course.
There is a ‘hands on’ approach to measuring parameters on spinal X Rays and the use of a software for digital images. The speakers will provide their expertise through didactic presentations and clinical cases precisely selected.
The program will also include breakout session to discuss clinical cases and their treatment options, according to sagittal balance parameters.
All participants are requested to bring their own cases well documented in a ppt format for open discussion.

Chronic subdural hematoma recurrence

Chronic subdural hematoma recurrence

Epidemiology

In 2 large cohorts of US patients, approximately 5% to 10% of patients who underwent surgery for nontraumatic SDH were required to undergo repeated operation within 30 to 90 days. These results may inform the design of future prospective studies and trials and help practitioners calibrate their index of suspicion to ensure that patients are referred for timely surgical care 1).

Recurrence rates after chronic subdural hematoma (CSDH) evacuation with any of actual techniques twist drillcraniostomy (TDC), burr hole craniostomy, craniotomy range from 5% to 30%. 2).

Risk factors

In the series of Han et al. independent risk factors for recurrence were as follows: age > 75 years (HR 1.72, 95% CI 1.03-2.88; p = 0.039), obesity (body mass index ≥ 25.0 kg/m2), and a bilateral operation 3).

Chon et al. shown that postoperative midline shifting (≥5 mm), diabetes mellitus, preoperative seizure, preoperative width of hematoma (≥20 mm), and anticoagulant therapy were independent predictors of the recurrence of chronic subdural hematoma.

According to internal architecture of hematoma, the rate of recurrence was significantly lower in the homogeneous and the trabecular type than the laminar and separated type 4).


The recurrence rate of chronic subdural hematoma cSDH seems to be related to the excessive neoangiogenesis in the parietal membrane, which is mediated via vascular endothelial growth factor (VEGF). This is found to be elevated in the hematoma fluid and is dependent on eicosanoid/prostaglandin and thromboxane synthesis via cyclooxygenase-2 (COX-2).

Anticoagulant therapy

Antiplatelet therapy

Antiplatelet therapy significantly influences the recurrence of CSDH 5).

Pneumocephalus

Remaining pneumocephalus is seen as an approved factor of recurrence 6) 7).

Septation

Jack et al.found a 12% reoperation rate. CSDH septation (seen on computed tomogram scan) was found to be an independent risk factor for recurrence requiring reoperation (p=0.04). Larger post-operative subdural haematoma volume was also significantly associated with requiring a second drainage procedure (p<0.001). Independent risk factors of larger post-operative haematoma volume included septations within a CSDH (p<0.01), increased pre-operative haematoma volume (p<0.01), and a greater amount of parenchymal atrophy (p=0.04). A simple scoring system for quantifying recurrence risk was created and validated based on patient age (< or ≥80 years), haematoma volume (< or ≥160cc), and presence of septations within the subdural collection (yes or no).

Septations within CSDHs are associated with larger post-operative residual haematoma collections requiring repeat drainage. When septations are clearly visible within a CSDH, craniotomy might be more suitable as a primary procedure as it allows greater access to a septated subdural collection. The proposed scoring system combining haematoma volume, age, and presence of septations might be useful in identifying patients at higher risk for recurrence 8).

Membranectomy

Opening the internal hematoma membrane does not alter the rate of patients requiring revision surgery and the number of patients showing a marked residual hematoma six weeks after evacuation of a CSDH 9).

In the study of Lee et al, an extended surgical approach with partial membranectomy has no advantages regarding the rate of reoperation and the outcome. As initial treatment, burr-hole drainage with irrigation of the hematoma cavity and closed-system drainage is recommended. Extended craniotomy with membranectomy is now reserved for instances of acute rebleeding with solid hematoma 10).

Diabetes

Surgeons should consider informing patients with diabetes mellitus that this comorbidity is associated with an increased likelihood of recurrence

11) 12) 13).


Balser et al. report 11% recurrence, which included individuals who recurred as late as 3 years after initial diagnosis 14).

Close imaging follow-up is important for CSDH patients for recurrence prediction. Using quantitative CT volumetric analysis, strong evidence was provided that changes in the residual fluid volume during the ‘self-resolution’ period can be used as significantly radiological predictors of recurrence 15).

A structural equation model showed a significant association between increased antiinflammatory activity in hematoma fluid samples and a lower risk of recurrence, but this relationship was not statistically significant in venous blood samples. Moreover, these findings indicate that anti-inflammatory activities in the hematoma may play a role in the risk of a recurrence of CSDH 16).

Irrigation with artificial cerebrospinal fluid (ACF) decreased the rate of CSDH recurrence 17).

Treatment

There is no definite operative procedure for patients with intractable chronic subdural hematoma (CSDH).

Most recurrent hematomas are managed successfully with burr hole craniostomies with postoperative closed-system drainage. Refractory hematomas may be managed with a variety of techniques, including craniotomy or subdural-peritoneal shunt placement 18).

Although many studies have reported risk factors or treatments in efforts to prevent recurrence, those have focused on single recurrence, and little cumulative data is available to analyze refractory CSDH.

Matsumoto et al. defined refractory CSDH as ≥2 recurrences, then analyzed and compared clinical factors between patients with single recurrence and those with refractory CSDH in a cohort study, to clarify whether patients with refractory CSDH experience different or more risk factors than patients with single recurrence, and whether burr-hole irrigation with closed-system drainage reduces refractory CSDH.

Seventy-five patients had at least one recurrence, with single recurrence in 62 patients and ≥2 recurrences in 13 patients. In comparing clinical characteristics, patients with refractory CSDH were significantly younger (P=0.04) and showed shorter interval to first recurrence (P<0.001). Organized CSDH was also significantly associated with refractory CSDH (P=0.02). Multivariate logistic regression analysis identified first recurrence interval <1 month (OR 6.66, P<0.001) and age <71 years (OR 4.16, P<0.001) as independent risk factors for refractory CSDH. On the other hand, burr-hole irrigation with closed-system drainage did not reduce refractory CSDH.

When patients with risk factors for refractory CSDH experience recurrence, alternative surgical procedures may be considered as the second surgery, because burr-hole irrigation with closed-system drainage did not reduce refractory CSDH 19).

Implantation of a reservoir 20) 21) 22).

Subdural-peritoneal shunt 23).

Middle meningeal artery embolization

Embolization of the MMA is effective for refractory CSDH or CSDH patients with a risk of recurrence, and is considered an effective therapeutic method to stop hematoma enlargement and promote resolution 24) 25) 26) 27) 28) 29).

A pilot study indicated that perioperative middle meningeal artery (MMA) embolization could be offered as the least invasive and most effectual means of treatment for resistant patients of CSDHs with 1 or more recurrences 30).

Chihara et al. have treated three cases of CSDH with MMA embolization to date, but there was a postoperative recurrence in one patient, which required a craniotomy for hematoma removal and capsulectomy. MMA embolization blocks the blood supply from the dura to the hematoma outer membrane in order to prevent recurrences of refractory CSDH. Histopathologic examination of the outer membrane of the hematoma excised during craniotomy showed foreign-body giant cells and neovascular proliferation associated with embolization. Because part of the hematoma was organized in this case, the CSDH did not resolve when the MMA was occluded, and the development of new collateral pathways in the hematoma outer membrane probably contributed to the recurrence. Therefore, in CSDH with some organized hematoma, MMA embolization may not be effective. Magnetic resonance imaging (MRI) should be performed in these patients before embolization 31).

Case series

Case reports

References

1)

Knopman J, Link TW, Navi BB, Murthy SB, Merkler AE, Kamel H. Rates of Repeated Operation for Isolated Subdural Hematoma Among Older Adults. JAMA Netw Open. 2018 Oct 5;1(6):e183737. doi: 10.1001/jamanetworkopen.2018.3737. PubMed PMID: 30646255.
2)

Escosa Baé M, Wessling H, Salca HC, de Las Heras Echeverría P. Use of twist-drill craniostomy with drain in evacuation of chronic subdural hematomas: independent predictors of recurrence. Acta Neurochir (Wien). 2011 May;153(5):1097-103. doi: 10.1007/s00701-010-0903-3. Epub 2010 Dec 31. PubMed PMID: 21193935.
3)

Han MH, Ryu JI, Kim CH, Kim JM, Cheong JH, Yi HJ. Predictive factors for recurrence and clinical outcomes in patients with chronic subdural hematoma. J Neurosurg. 2017 Nov;127(5):1117-1125. doi: 10.3171/2016.8.JNS16867. Epub 2016 Dec 16. PubMed PMID: 27982768.
4)

Chon KH, Lee JM, Koh EJ, Choi HY. Independent predictors for recurrence of chronic subdural hematoma. Acta Neurochir (Wien). 2012 Sep;154(9):1541-8. doi: 10.1007/s00701-012-1399-9. Epub 2012 Jun 1. PubMed PMID: 22653496.
5)

Wada M, Yamakami I, Higuchi Y, Tanaka M, Suda S, Ono J, Saeki N. Influence of antiplatelet therapy on postoperative recurrence of chronic subdural hematoma: a multicenter retrospective study in 719 patients. Clin Neurol Neurosurg. 2014 May;120:49-54. doi: 10.1016/j.clineuro.2014.02.007. Epub 2014 Feb 24. PubMed PMID: 24731576.
6)

Mori K, Maeda M (2001) Surgical treatment of chronic subdural hematoma in 500 consecutive cases: clinical characteristics, surgical outcome, complications, and recurrence rate. Neurol Med Chir (Tokyo) 41:371–381
7)

Stanišić M, Hald J, Rasmussen IA, Pripp AH, Ivanović J, Kolstad F, Sundseth J, Züchner M, Lindegaard KF (2013) Volume and densities of chronic subdural haematoma obtained from CT imaging as predictors of postoperative recurrence: a prospective study of 107 operated patients. Acta Neurochir 155:323–333
8)

Jack A, O’Kelly C, McDougall C, Max Findlay J. Predicting Recurrence after Chronic Subdural Haematoma Drainage. Can J Neurol Sci. 2015 Jan 5:1-6. [Epub ahead of print] PubMed PMID: 25557536.
9)

Unterhofer C, Freyschlag CF, Thomé C, Ortler M. Opening the Internal Hematoma Membrane does not Alter the Recurrence Rate of Chronic Subdural Hematomas – A Prospective Randomized Trial. World Neurosurg. 2016 May 2. pii: S1878-8750(16)30210-8. doi: 10.1016/j.wneu.2016.04.081. [Epub ahead of print] PubMed PMID: 27150644.
10)

Lee JY, Ebel H, Ernestus RI, Klug N. Various surgical treatments of chronic subdural hematoma and outcome in 172 patients: is membranectomy necessary? Surg Neurol. 2004 Jun;61(6):523-7; discussion 527-8. PubMed PMID: 15165784.
11)

Matsumoto K, Akagi K, Abekura M, Ryujin H, Ohkawa M, Iwasa N, Akiyama C. Recurrence factors for chronic subdural hematomas after burr-hole craniostomy and closed system drainage. Neurol Res. 1999 Apr;21(3):277-80. PubMed PMID: 10319336.
12)

Yamamoto H, Hirashima Y, Hamada H, Hayashi N, Origasa H, Endo S. Independent predictors of recurrence of chronic subdural hematoma: results of multivariate analysis performed using a logistic regression model. J Neurosurg. 2003 Jun;98(6):1217-21. PubMed PMID: 12816267.
13)

Pang CH, Lee SE, Kim CH, Kim JE, Kang HS, Park CK, Paek SH, Kim CH, Jahng TA, Kim JW, Kim YH, Kim DG, Chung CK, Jung HW, Yoo H. Acute intracranial bleeding and recurrence after bur hole craniostomy for chronic subdural hematoma. J Neurosurg. 2015 Jul;123(1):65-74. doi: 10.3171/2014.12.JNS141189. Epub 2015 Feb 13. PubMed PMID: 25679282.
14)

Balser D, Rodgers SD, Johnson B, Shi C, Tabak E, Samadani U. Evolving management of symptomatic chronic subdural hematoma: experience of a single institution and review of the literature. Neurol Res. 2013 Apr;35(3):233-42. doi: 10.1179/1743132813Y.0000000166. Review. PubMed PMID: 23485050.
15)

Xu FF, Chen JH, Leung GK, Hao SY, Xu L, Hou ZG, Mao X, Shi GZ, Li JS, Liu BY. Quantitative computer tomography analysis of post-operative subdural fluid volume predicts recurrence of chronic subdural haematoma. Brain Inj. 2014;28(8):1121-6. doi: 10.3109/02699052.2014.910702. Epub 2014 May 6. PubMed PMID: 24801643.
16)

Pripp AH, Stanišić M. The Correlation between Pro- and Anti-Inflammatory Cytokines in Chronic Subdural Hematoma Patients Assessed with Factor Analysis. PLoS One. 2014 Feb 27;9(2):e90149. doi: 10.1371/journal.pone.0090149. eCollection 2014. PubMed PMID: 24587250.
17)

Adachi A, Higuchi Y, Fujikawa A, Machida T, Sueyoshi S, Harigaya K, Ono J, Saeki N. Risk factors in chronic subdural hematoma: comparison of irrigation with artificial cerebrospinal fluid and normal saline in a cohort analysis. PLoS One. 2014 Aug 4;9(8):e103703. doi: 10.1371/journal.pone.0103703. eCollection 2014. PubMed PMID: 25089621; PubMed Central PMCID: PMC4121178.
18)

Desai VR, Scranton RA, Britz GW. Management of Recurrent Subdural Hematomas. Neurosurg Clin N Am. 2017 Apr;28(2):279-286. doi: 10.1016/j.nec.2016.11.010. Epub 2017 Jan 4. Review. PubMed PMID: 28325462.
19)

Matsumoto H, Hanayama H, Okada T, Sakurai Y, Minami H, Masuda A, Tominaga S, Miyaji K, Yamaura I, Yoshida Y, Yoshida K. Clinical investigation of refractory chronic subdural hematoma: a comparison of clinical factors between single and repeated recurrences. World Neurosurg. 2017 Aug 24. pii: S1878-8750(17)31402-X. doi: 10.1016/j.wneu.2017.08.101. [Epub ahead of print] PubMed PMID: 28844917.
20)

Sato M, Iwatsuki K, Akiyama C, Masana Y, Yoshimine T, Hayakawa T. [Use of Ommaya CSF reservoir for refractory chronic subdural hematoma]. No Shinkei Geka. 1999 Apr;27(4):323-8. Japanese. PubMed PMID: 10347846.
21)

Sato M, Iwatsuki K, Akiyama C, Kumura E, Yoshimine T. Implantation of a reservoir for refractory chronic subdural hematoma. Neurosurgery. 2001 Jun;48(6):1297-301. PubMed PMID: 11383733.
22)

Laumer R. Implantation of a reservoir for refractory chronic subdural hematoma. Neurosurgery. 2002 Mar;50(3):672. PubMed PMID: 11841742.
23)

Misra M, Salazar JL, Bloom DM. Subdural-peritoneal shunt: treatment for bilateral chronic subdural hematoma. Surg Neurol. 1996 Oct;46(4):378-83. PubMed PMID: 8876720.
24)

Mandai S, Sakurai M, Matsumoto Y. Middle meningeal artery embolization for refractory chronic subdural hematoma. Case report. J Neurosurg. 2000 Oct;93(4):686-8. PubMed PMID: 11014549.
25)

Takahashi K, Muraoka K, Sugiura T, Maeda Y, Mandai S, Gohda Y, Kawauchi M, Matsumoto Y. [Middle meningeal artery embolization for refractory chronic subdural hematoma: 3 case reports]. No Shinkei Geka. 2002 May;30(5):535-9. Japanese. PubMed PMID: 11993178.
26)

Hirai S, Ono J, Odaki M, Serizawa T, Nagano O. Embolization of the Middle Meningeal Artery for Refractory Chronic Subdural Haematoma. Usefulness for Patients under Anticoagulant Therapy. Interv Neuroradiol. 2004 Dec 24;10 Suppl 2:101-4. Epub 2008 May 15. PubMed PMID: 20587257; PubMed Central PMCID: PMC3522210.
27)

Tsukamoto Y, Oishi M, Shinbo J, Fujii Y. Transarterial embolisation for refractory bilateral chronic subdural hematomas in a case with dentatorubral-pallidoluysian atrophy. Acta Neurochir (Wien). 2011 May;153(5):1145-7. doi: 10.1007/s00701-010-0891-3. Epub 2010 Dec 2. PubMed PMID: 21125409.
28)

Mino M, Nishimura S, Hori E, Kohama M, Yonezawa S, Midorikawa H, Kaimori M, Tanaka T, Nishijima M. Efficacy of middle meningeal artery embolization in the treatment of refractory chronic subdural hematoma. Surg Neurol Int. 2010 Dec 13;1:78. doi: 10.4103/2152-7806.73801. PubMed PMID: 21206540; PubMed Central PMCID: PMC3011107.
29)

Hashimoto T, Ohashi T, Watanabe D, Koyama S, Namatame H, Izawa H, Haraoka R, Okada H, Ichimasu N, Akimoto J, Haraoka J. Usefulness of embolization of the middle meningeal artery for refractory chronic subdural hematomas. Surg Neurol Int. 2013 Aug 19;4:104. doi: 10.4103/2152-7806.116679. eCollection 2013. PubMed PMID: 24032079; PubMed Central PMCID: PMC3766342.
30)

Kim E. Embolization Therapy for Refractory Hemorrhage in Patients with Chronic Subdural Hematomas. World Neurosurg. 2017 May;101:520-527. doi: 10.1016/j.wneu.2017.02.070. Epub 2017 Feb 27. PubMed PMID: 28249828.
31)

Chihara H, Imamura H, Ogura T, Adachi H, Imai Y, Sakai N. Recurrence of a Refractory Chronic Subdural Hematoma after Middle Meningeal Artery Embolization That Required Craniotomy. NMC Case Rep J. 2014 May 9;1(1):1-5. doi: 10.2176/nmccrj.2013-0343. eCollection 2014 Oct. PubMed PMID: 28663942; PubMed Central PMCID: PMC5364934.

Adverse event

Adverse event (AE)

An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

see also complications.

see MAUDE.

Risk of intraop AEs, but not postop AEs, increased with increasing age. Having multiple comorbidities does not predispose to more AEs. Infections predominate among the postop AEs. Patients at increased risk of delirium or of having an increased length of hospital stay may more easily be predicted. Studies specifically designed to prospectively assess AEs have the potential to more accurately identify postop AE rates 1).

see National Cancer Institutes Common Terminology Criteria for Adverse Events

Epidemiology

Adverse events reportedly occur in 5% to 10% of health care episodes.

A follow-up study examining 8 years of reported surgical adverse events and root causes from US Veterans Health Administration (VHA) medical centers, compared with the previous studies of 2001 to 2006 and 2006 to 2009, and to recommend actions for future prevention of such events.

This quality improvement study described patient safety adverse events and close calls reported from 86 VHA medical centers from the approximately 130 VHA facilities with a surgical program. The surgical procedures and programs vary in size and complexity from small rural centers to large, complex urban facilities. Procedures occurring between January 1, 2010, and December 31, 2017, were included. Data analysistook place in 2018.

The categories of incorrect procedure types were wrong patient, side, site (including wrong-level spine), procedure, or implant. Events included those in or out of the operating room, adverse events or close calls, surgical specialty, and harm. These results were compared with the previous studies of VHA-reported wrong-site surgery (2001-2006 and 2006-2009).

The review produced 483 reports (277 adverse events and 206 close calls). The rate of in-operating room (in-OR) reported adverse events with harm has continued to trend downward from 1.74 to 0.47 reported adverse events with harm per 100 000 procedures between 2000 and 2017 based on 6 591 986 in-OR procedures. When in-OR events were examined by discipline as a rate, dentistry had 1.54, neurosurgery had 1.53, and ophthalmology had 1.06 reported in-OR adverse events per 10 000 cases. The overall VHA in-OR rate for adverse events during 2010 to 2017 was 0.53 per 10 000 procedures based on 3 234 514 in-OR procedures. The most common root cause for adverse events was related to issues in performing a comprehensive time-out (28.4%). In these cases, the time-out either was conducted incorrectly or was incomplete in some way.

Over the period studied, the VHA identified a decrease in the rate of reported adverse events in the OR associated with harm and continued reporting of adverse event close calls. Organizational efforts continue to examine root cause analysis reports, promulgate lessons learned, and enhance policy to promote a culture and behavior that minimizes events and is transparent in reporting occurrences 2).

Etiology

Not all adverse events are the result of error; they may arise from systemic faults in the delivery of health care. Catastrophic events are not only physically devastating to patients, but they also attract medical liability and increase health care costs. Root cause analysis (RCA) has become a key tool for health care services to understand those adverse events.

It is well recognized that the occurrence rate of adverse events related to surgical procedures is considerably high in neurosurgery compared with other specialties.

Adverse events during diagnostic and therapeutic procedures and medical errors associated with them are an important source of patient morbidity. In an attempt to reduce these, the WHO has proposed a series of measures applicable to medical and surgical patients. Within these last ones is the surgical safety checklist (SSC), a brief questionnaire that does not increase healthcare costs, is accessible to all surgical centres and can be adapted to each specific environment.

One hundred eighty-two events (28.3%) among 643 neurosurgical interventions over 2 years were recognized as adverse events. Among these 182 adverse events, 165 (90.7%) were closely related to procedures and 125 events (68.7%) were predictable before or during the procedures. However, even when retrospectively reviewed, only 6 (3.3%) of events were deemed avoidable. Of these 6 avoidable events, there were only 2 (1.1%) that were considered to have been caused by error.

Adverse events are not invariably rare in neurosurgery. Most of them are predictable; however, their avoidance is not necessarily easy. Avoidable adverse events caused by medical errors were observed in only 1.1% of cases 3).

Undesired harmful effect resulting from a medication or other intervention such as surgery.

An adverse effect may be termed a “side effect”, when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or procedure, this is called a medical error and not a complication. Adverse effects are sometimes referred to as “iatrogenic” because they are generated by a physician/treatment. Some adverse effects occur only when starting, increasing or discontinuing a treatment.

Using a drug or other medical intervention which is contraindicated may increase the risk of adverse effects. Adverse effects may cause complications of a disease or procedure and negatively affect its prognosis. They may also lead to non-compliance with a treatment regimen.

The harmful outcome is usually indicated by some result such as morbidity, mortality, alteration in body weight, levels of enzymes, loss of function, or as a pathological change detected at the microscopic, macroscopic or physiological level. It may also be indicated by symptoms reported by a patient. Adverse effects may cause a reversible or irreversible change, including an increase or decrease in the susceptibility of the individual to other chemicals, foods, or procedures, such as drug interactions.

see Side error.

Spine adverse events

References

1)

Kelly AM, Batke JN, Dea N, Hartig DP, Fisher CG, Street JT. Prospective analysis of adverse events in surgical treatment of degenerative spondylolisthesis. Spine J. 2014 Dec 1;14(12):2905-10. doi: 10.1016/j.spinee.2014.04.016. Epub 2014 Apr 21. PubMed PMID: 24769400.
2)

Neily J, Soncrant C, Mills PD, Paull DE, Mazzia L, Young-Xu Y, Nylander W, Lynn MM, Gunnar W. Assessment of Incorrect Surgical Procedures Within and Outside the Operating Room: A Follow-up Study From US Veterans Health Administration Medical Centers. JAMA Netw Open. 2018 Nov 2;1(7):e185147. doi: 10.1001/jamanetworkopen.2018.5147. PubMed PMID: 30646381.
3)

Houkin K, Baba T, Minamida Y, Nonaka T, Koyanagi I, Iiboshi S. Quantitative analysis of adverse events in neurosurgery. Neurosurgery. 2009 Sep;65(3):587-94; discussion 594. doi: 10.1227/01.NEU.0000350860.59902.68. PubMed PMID: 19687705.

Prader–Willi syndrome

Prader–Willi syndrome

Prader–Willi syndrome (PWS) is a genetic disorder due to loss of function of specific genes.

In newborns, symptoms include weak muscles, poor feeding, and slow development.

Beginning in childhood, the person becomes constantly hungry, which often leads to obesity and type 2 diabetes.

Also, mild to moderate intellectual impairment and behavioral problems are typical.

Often, the forehead is narrow, hands and feet are small, height is short, skin is light in color, and most of the affected are unable to have children.

About 74% of cases occur when part of the father’s chromosome 15 is deleted.

In another 25% of cases, the person has two copies of chromosome 15 from their mother and none from their father.

As parts of the chromosome from the mother are turned off, they end up with no working copies of certain genes.

PWS is not generally inherited, but instead the genetic changes happen during the formation of the egg, sperm, or in early development.


Franco et al., presented case series from the Hospital das Clínicas. Four patients with genetically confirmed Prader-Willi syndrome (PWS) presenting with severe obesity were included.

Deep brain stimulation electrodes were bilaterally implanted in the lateral hypothalamic area. After DBS implantation, the treatment included the following phases: titration (1-2 months), stimulation off (2 months), low-frequency DBS (40 Hz; 1 month), washout (15 days), high-frequency DBS (130 Hz; 1 month), and long-term follow-up (6 months).

Primary outcome measures were adverse eventrecorded during stimulation and long-term DBS treatment. Secondary outcomes consisted of changes in anthropometric measures (weightbody mass index [calculated as weight in kilograms divided by height in meters squared], and abdominal and neck circumference), bioimpedanciometry, and calorimetry after 6 months of treatment compared with baseline. The following evaluations and measurements were conducted before and after DBS: clinical, neurological, psychiatric, neuropsychological, anthropometry, calorimetry, blood workup, hormonal levels, and sleep studies. Adverse effects were monitored during all follow-up visits.

Four patients with PWS were included (2 male and 2 female; ages 18-28 years). Baseline mean (SD) body mass index was 39.6 (11.1). Two patients had previous bariatric surgery, and all presented with psychiatric comorbidity, which was well controlled with the use of medications. At 6 months after long-term DBS, patients had a mean 9.6% increase in weight, 5.8% increase in body mass index, 8.4% increase in abdominal circumference, 4.2% increase in neck circumference, 5.3% increase in the percentage of body fat, and 0% change in calorimetry compared with baseline. Also unchanged were hormonal levels and results of blood workup, sleep studies, and neuropsychological evaluations. Two patients developed stimulation-induced manic symptoms. Discontinuation of DBS controlled this symptom in 1 patient. The other required adjustments in medication dosage. Two infections were documented, 1 associated with skin picking.

Safety of lateral hypothalamic area stimulation was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS. In the small cohort of patients with PWS treated in the study, DBS was largely ineffective 1).


Lateral hypothalamic area (LHA) local field potentials (LFPs) were recorded in a Prader-Willi patient undergoing deep brain stimulation (DBS) for obesity. During hunger, exposure to food-related cues induced an increase in beta/low-gamma activity. In contrast, recordings during satiety were marked by prominent alpha rhythms. Based on these findings, Talakoub et al., delivered alpha-frequency DBS prior to and during food intake. Despite reporting an early sensation of fullness, the patient continued to crave food. This suggests that the pattern of activity in LHA may indicate hunger/satiety states in humans but attest to the complexity of conducting neuromodulation studies in obesity 2).

References

1)

Franco RR, Fonoff ET, Alvarenga PG, Alho EJL, Lopes AC, Hoexter MQ, Batistuzzo MC, Paiva RR, Taub A, Shavitt RG, Miguel EC, Teixeira MJ, Damiani D, Hamani C. Assessment of Safety and Outcome of Lateral Hypothalamic Deep Brain Stimulation for Obesity in a Small Series of Patients With Prader-Willi Syndrome. JAMA Netw Open. 2018 Nov 2;1(7):e185275. doi: 10.1001/jamanetworkopen.2018.5275. PubMed PMID: 30646396.
2)

Talakoub O, Paiva RR, Milosevic M, Hoexter MQ, Franco R, Alho E, Navarro J, Pereira JF Jr, Popovic MR, Savage C, Lopes AC, Alvarenga P, Damiani D, Teixeira MJ, Miguel EC, Fonoff ET, Batistuzzo MC, Hamani C. Lateral hypothalamic activity indicates hunger and satiety states in humans. Ann Clin Transl Neurol. 2017 Oct 20;4(12):897-901. doi: 10.1002/acn3.466. eCollection 2017 Dec. PubMed PMID: 29296618; PubMed Central PMCID: PMC5740250.

Diffuse astrocytoma

Diffuse astrocytoma

Types

Diffuse astrocytoma IDH Mutant 9400/3

Gemistocytic astrocytoma 9411/3

Diffuse astrocytoma IDH wild type 9400/3

Diffuse astrocytoma NOS 9400/3


WHO grade determinations are still made on the basis of histologic criteria. Another reason why phenotype remains essential is that, there are individual tumors that do not meet the more narrowly defined phenotype and genotype criteria, e.g., the rare phenotypically classical diffuse astrocytoma that lacks the signature genetic characteristics of IDH and ATRX mutations. Nevertheless, it remains possible that future WHO classifications of the diffuse gliomas, in the setting of deeper and broader genomic capabilities, will require less histological evaluation—perhaps only a diagnosis of “diffuse glioma.” For now, the World Health Organization Classification of Tumors of the Central Nervous System 2016 is predicated on the basis of combined phenotypic and genotypic classification, and on the generation of “integrated” diagnoses.

Diffuse astrocytoma and oligodendrogliomas are in this classification now nosologically more similar than are diffuse astrocytoma and pilocytic astrocytoma; the family trees have been redrawn.

In the setting of a diffuse astrocytoma or anaplastic astrocytoma, if IDH testing is not available or cannot be fully performed (e.g., negative immunohistochemistry without available sequencing), the resulting diagnosis would be diffuse astroctyoma, NOS, or anaplastic astrocytoma, NOS, respectively.

Historically, the prognostic differences between WHO grade II diffuse astrocytomas and WHO grade III anaplastic astrocytomas were highly significant.

Some studies, however, have suggested that the prognostic differences between IDH-mutant WHO grade II diffuse astrocytomas and IDH-mutant WHO grade III anaplastic astrocytomas are not as marked.

Nonetheless, this has not been noted in all studies. At this time, it is recommended that WHO grading is retained for both IDH-mutant and IDH-wildtype astrocytomas, although the prognosis of the IDH-mutant cases appears more favorable in both grades. Cautionary notes have been added to the 2016 classification in this regard.

Of note, two diffuse astrocytoma variants have been deleted from the WHO classification: protoplasmic astrocytoma, a diagnosis that was previously defined in only vague terms and is almost never made any longer given that tumors with this histological appearance are typically characterized as other more narrowly defined lesions; and fibrillary astrocytoma, since this diagnosis overlaps nearly entirely with the standard diffuse astrocytoma. As a result, only gemistocytic astrocytoma remains as a distinct variant of diffuse astrocytoma IDH-mutant.

Outcome

For the diffuse astrocytomas, there have been many such studies over the past century and these have proven useful in estimating prognosis for patients. With the advent of molecular diagnostics and the recent World Health Organization (WHO) Classification of Tumors of the Central Nervous System it is necessary testing for isocitrate dehydrogenase (IDH) gene status in the classification of diffuse astrocytic gliomas. Novel approaches to diffuse astrocytic tumor grading are required in the era of IDH testing 1).


Alattar et al. determined the influence of age and tumor location on survival benefit from GTR in diffuse astrocytoma (DA).

They used The Surveillance, Epidemiology and End Results (SEER) database (1999-2010). They used Kaplan-Meier curves and Cox survival models to determine the survival benefit from GTR in populations stratified by age and tumor location. They determined the prevalence of the IDH mutation (mIDH) using The Cancer Genome Atlas (TCGA).

They identified 1980 patients with DA. For frontal DAs, GTR resulted in improved survival relative to subtotal resection in all ages (age ≤50 years hazard ratio [HR], 0.56; P = 0.002; age >50 years HR, 0.41; P < 0.001). For nonfrontal DAs, only patients ≤50 years experienced improved survival with GTR (age ≤50 years HR, 0.55; P = 0.002; age >50 years HR, 0.78; P = 0.114). For patients ≤50 years with frontal tumors, survival was comparable between DA and AA after GTR (75% survival DA: 80 months, AA: 89 months, P = 0.973). In TCGA, these tumors were nearly uniformly mIDH (DA: 98%; AA: 90%, P = 0.11). However, for patients ≤50 years with nonfrontal tumors, there was a survival difference after GTR (75% survival DA: 80 months, AA: 30 months, P = 0.001) despite comparable mIDH prevalence (DA: 82%, AA: 75%, P = 0.49).

Age and tumor location modify the survival benefit derived from GTR in DA. Survival patterns in SEER imperfectly correlated with mIDH prevalence in TCGA, suggesting that tumor grade and mIDH status convey nonredundant prognostic information in select clinical contexts 2).

References

1)

von Deimling A, Ono T, Shirahata M, Louis DN. Grading of Diffuse Astrocytic Gliomas: A Review of Studies Before and After the Advent of IDH Testing. Semin Neurol. 2018 Feb;38(1):19-23. doi: 10.1055/s-0038-1636430. Epub 2018 Mar 16. PubMed PMID: 29548048.
2)

Alattar AA, Carroll KT, Bryant AK, Hirshman B, Joshi R, Carter BS, Harismendy O, Chen CC. Prognostic Importance of Age, Tumor Location, and Tumor Grade in Grade II Astrocytomas: An Integrated Analysis of the Cancer Genome Atlas and the Surveillance, Epidemiology, and End Results Database. World Neurosurg. 2019 Jan;121:e411-e418. doi: 10.1016/j.wneu.2018.09.124. Epub 2018 Sep 26. PubMed PMID: 30266697.

Non small cell lung cancer intracranial metastases treatment

Non small cell lung cancer intracranial metastases treatment

Brain metastases are common in patients with non small cell lung cancer (NSCLC). Because of associated poor prognosis and limited specific treatment options, there is a real need for the development of medical therapies and strategies for affected patients. Novel compounds for epidermal growth factor receptor-dependent and anaplastic lymphoma kinase-dependent lung cancer have demonstrated blood-brain barrier permeability and have led to important improvements in central nervous system outcomes. Studies of targeted therapies for oncogene-driven tumors and of immunotherapies in patients with brain metastases have shown promise and, allied with novel radiation techniques, are driving a rapid evolution in treatment and prognosis for NSCLC brain metastases 1).


KPS score ≥ 70, RPA class I/II, and postoperative chemotherapy could benefit post-metastasectomy patients with brain metastases (BM) from Non small cell lung cancer (NSCLC). Conversely, the initial onset of intracranial lesions is an unfavorable factor that increases the risk of death. These findings support the use of personalized therapy for patients with BM from NSCLC 2).


EGFR and ALK tyrosine kinase inhibitors (TKIs) provide significantly superior systemic response rates and progression free survival compared to standard chemotherapy in the molecularly defined Non small cell lung cancer (NSCLC) subpopulations. An apparent intracranial activity of new generation TKIs triggered the discussion on their role in brain metastases in lieu of local therapies 3).


A article of Preusser et al., is the result of a round table discussion held at the European Lung Cancer Conference (ELCC) in Geneva in May 2017. Its purpose was to explore and discuss the advances in the knowledge about the biology and treatment of brain metastases originating from non-small cell lung cancer. The authors propose a series of recommendations for research and treatment within the discussed context 4).


PUBMEDEMBASE, the Cochrane LibraryWeb of Knowledge, Current Controlled Trials, Clinical Trials, and 2 conference websites were searched to select NSCLC patients with only single brain metastasis (SBM) who received brain surgery or SRS. SPSS 18.0 software was used to analyze the mean median survival time (MST) and Stata 11.0 software was used to calculate the overall survival (OS).

A total of 18 trials including 713 patients were systematically reviewed. The MST of the patients was 12.7 months in surgery group and 14.85 months in SRS group, respectively. The 1, 2, and 5 years OS of the patients were 59%, 33%, and 19% in surgery group, and 62%, 33%, and 14% in SRS group, respectively. Furthermore, in the surgery group, the 1 and 3 years OS were 68% and 15% in patients with controlled primary tumors, and 50% and 13% in the other patients with uncontrolled primary tumors, respectively. Interestingly, the 5-year OS was up to 21% in patients with controlled primary tumors.

There was no significant difference in MST or OS between patients treated with neurosurgery and SRS. Patients with resectable lung tumors and SBM may benefit from the resection of both primary lesions and metastasis 5).

Patients with NSCLC and synchronous brain metastases, presenting neurological symptoms showed no survival benefit from neurosurgical resection, although quality of life was improved due to early control of neurological symptoms 6).


Response rates after platinum based antineoplastics, range from 23% to 45%. Development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs): gefitinib or erlotinib, was an improvement in treatment of advanced NSCLC patients. EGFR mutations are present in 10-25% of NSCLC (mostly adenocarcinoma), and up to 55% in never-smoking women of East Asian descent. In the non-selected group of patients with BMF-NSCLC, the overall response rates after gefitinib or erlotinib treatment range from 10% to 38%, and the duration of response ranges from 9 to 13.5 months. In the case of present activating EGFR mutation, the response rate after EGRF-TKIs is greater than 50%, and in selected groups (adenocarcinoma, patients of Asian descent, never-smokers, asymptomatic BMF-NSCLC) even 70%. Gefitinib or erlotinib treatment improves survival of BMF-NSCLC patients with EGFR mutation in comparison to cases without the presence of this mutation. There is no data on the activity of the anti-EML4-ALK agent crizotinib. Bevacizumab, recombinant humanised monoclonal antibody anti-VEGF, in the treatment of advanced non-squamous NSCLC patients is a subject of intense research. Data from a clinical trial enrolling patients with pretreated or occult BMF-NSCLC proved that the addition of bevacizumab to various chemotherapy agents or erlotinib is a safe and efficient treatment, associated with a low incidence of CSN haemorrhages. However, the efficacy and safety of bevacizumab used for therapeutic intent, regarding active brain metastases is unknown 7).

Non small cell lung cancer intracranial metastases whole brain radiotherapy

Non small cell lung cancer intracranial metastases radiosurgery

Non small cell lung cancer intracranial metastases surgery

References

1)

Bulbul A, Forde PM, Murtuza A, Woodward B, Yang H, Bastian I, Ferguson PK, Lopez-Diaz F, Ettinger DS, Husain H. Systemic Treatment Options for Brain Metastases from Non-Small-Cell Lung Cancer. Oncology (Williston Park). 2018 Apr 15;32(4):156-63. Review. PubMed PMID: 29684234.
2)

She C, Wang R, Lu C, Sun Z, Li P, Yin Q, Liu Q, Wang P, Li W. Prognostic factors and outcome of surgically treated patients with brain metastases of non-small cell lung cancer. Thorac Cancer. 2018 Nov 28. doi: 10.1111/1759-7714.12913. [Epub ahead of print] PubMed PMID: 30485664.
3)

Wrona A, Dziadziuszko R, Jassem J. Management of brain metastases in non-small cell lung cancer in the era of tyrosine kinase inhibitors. Cancer Treat Rev. 2018 Dec;71:59-67. doi: 10.1016/j.ctrv.2018.10.011. Epub 2018 Oct 21. Review. PubMed PMID: 30366200.
4)

Preusser M, Winkler F, Valiente M, Manegold C, Moyal E, Widhalm G, Tonn JC, Zielinski C. Recent advances in the biology and treatment of brain metastases of non-small cell lung cancer: summary of a multidisciplinary roundtable discussion. ESMO Open. 2018 Jan 26;3(1):e000262. doi: 10.1136/esmoopen-2017-000262. eCollection 2018. Review. PubMed PMID: 29387475; PubMed Central PMCID: PMC5786916.
5)

Qin H, Wang C, Jiang Y, Zhang X, Zhang Y, Ruan Z. Patients with single brain metastasis from non-small cell lung cancer equally benefit from stereotactic radiosurgery and surgery: a systematic review. Med Sci Monit. 2015 Jan 12;21:144-52. doi: 10.12659/MSM.892405. PubMed PMID: 25579245.
6)

Kim SY, Hong CK, Kim TH, Hong JB, Park CH, Chang YS, Kim HJ, Ahn CM, Byun MK. Efficacy of surgical treatment for brain metastasis in patients with non-small cell lung cancer. Yonsei Med J. 2015 Jan 1;56(1):103-11. doi: 10.3349/ymj.2015.56.1.103. PubMed PMID: 25510753; PubMed Central PMCID: PMC4276743.
7)

Cedrych I, Kruczała MA, Walasek T, Jakubowicz J, Blecharz P, Reinfuss M. Systemic treatment of non-small cell lung cancer brain metastases. Contemp Oncol (Pozn). 2016;20(5):352-357. doi: 10.5114/wo.2016.64593. Epub 2016 Dec 20. Review. PubMed PMID: 28373815; PubMed Central PMCID: PMC5371701.

VIM targeting

VIM targeting

The ventral intermediate nucleus of the thalamus is not readily visible on structural magnetic resonance imaging. Therefore, a method for its visualization for stereotactictargeting is desirable.

The objective of a study of Sammartino et al., from the Toronto Western Hospital was to define a tractography-based methodology for the stereotactic targeting of the ventral intermediate nucleus.

The lateral and posterior borders of the ventral intermediate nucleus were defined by tracking the pyramidal tract and medial lemniscus, respectively. A thalamic seed was then created 3 mm medial and anterior to these borders, and its structural connections were analyzed. The application of this method was assessed in an imaging cohort of 14 tremorpatients and 15 healthy controls, in which they compared the tractography-based targeting to conventional targeting. In a separate surgical cohort (3 tremor and 3 tremor-dominant Parkinson’s disease patients), they analyzed the accuracy of this method by correlating it with intraoperativeneurophysiology.

Tractography of the thalamic seed revealed the tracts corresponding to cerebellar input and motor cortical output fibers. The tractography-based target was more lateral (12.5 [1.2] mm vs 11.5 mm for conventional targeting) and anterior (8.5 [1.1] mm vs 6.7 [0.3] mm, anterior to the posterior commissure). In the surgical cohort, the Euclidean distance between the ventral intermediate nucleus identified by tractography and the surgical target was 1.6 [1.1] mm. The locations of the sensory thalamus, lemniscus, and pyramidal tracts were concordant within <1 mm between tractography and neurophysiology.

The tractography-based methodology for identification of the ventral intermediate nucleus is accurate and useful. This method may be used to improve stereotactic targeting in functional neurosurgery procedures 1).


Krishna et al., from the Center for Neuromodulation, The Ohio State University Wexner Medical Center,prospectively assessed the outcomes of Focused ultrasound thalamotomy (FUS-T) in 10 essential tremor (ET) patients using tractography-based targeting of the ventral intermediate nucleus (VIM).

VIM was identified at the intercommissural plane based on its neighboring tracts: the pyramidal tract and medial lemniscus. FUS-T was performed at the center of tractography-defined VIM. Tremor outcomes, at baseline and 3 months, were assessed independently by the Tremor Research Group. They analyzed targeting coordinates, clinical outcomes, and adverse events. The FUS-T lesion location was analyzed in relation to unbiased thalamic parcellation using probabilistic tractography. Quantitative diffusion weighted imaging changes were also studied in fiber tracts of interest.

The tractography coordinates were more anterior than the standard. Intraoperatively, therapeutic sonications at the tractography target improved tremor (>50% improvement) without motor or sensory side effects. Sustained improvement in tremor was observed at 3 mo (tremor score: 18.3 ± 6.9 vs 8.1 ± 4.4, P = .001). No motor weakness and sensory deficits after FUS-T were observed during 6-mo follow-up. Ataxia was observed in 3 patients. FUS-T lesions overlapped with the VIM parcellated with probablisitic tractography. Significant microstructural changes were observed in the white matter connecting VIM with cerebellum and motor cortex.

This is the first report of prospective VIM targeting with tractography for FUS-T. These results suggest that tractography-guided targeting is safe and has satisfactory short-term clinical outcomes 2).

Clinical trials

Optimization of VIM Targeting in Essential Tremor Surgery (Opti-VIM) https://clinicaltrials.gov/ct2/show/NCT03760406

References

1)

Sammartino F, Krishna V, King NK, Lozano AM, Schwartz ML, Huang Y, Hodaie M. Tractography-Based Ventral Intermediate Nucleus Targeting: Novel Methodology and Intraoperative Validation. Mov Disord. 2016 Aug;31(8):1217-25. doi: 10.1002/mds.26633. Epub 2016 May 23. PubMed PMID: 27214406; PubMed Central PMCID: PMC5089633.
2)

Krishna V, Sammartino F, Agrawal P, Changizi BK, Bourekas E, Knopp MV, Rezai A. Prospective Tractography-Based Targeting for Improved Safety of Focused Ultrasound Thalamotomy. Neurosurgery. 2019 Jan 1;84(1):160-168. doi: 10.1093/neuros/nyy020. PubMed PMID: 29579287.

Fluorescence-Guided Neurosurgery

Fluorescence-Guided Neurosurgery

see 5 aminolevulinic acid fluorescence guided resection.

see Fluorescein sodium guided resection.

see Fluorescence guided surgery of glioma.

The first use of fluorescence for brain tumour surgery was in 1948 by G.E. Moore 1) using fluorescein sodium.

Achieving a maximal safe extent of resection during brain tumor surgery is the goal for improved patient prognosisFluorescence-guided neurosurgery using 5-aminolevulinic acid (5-ALA) induced Protoporphyrin IX has thereby become a valuable tool enabling a high frequency of complete resections and a prolonged progression free survival in glioblastoma patients.

Erkkilä et al., from the Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Advanced Development Microsurgery, Carl Zeiss Meditec AG, Christian Doppler Laboratory for Innovative Optical Imaging and Its Translation to Medicine, Medical University of Vienna, Institute of Neurology, Department of Neurosurgery, General Hospital and Medical University of Vienna, presented a widefield fluorescence lifetime imaging device with 250 mm working distance working under similar conditions like surgical microscopes based on a time-of-flight based dual tap CMOS camera. In contrast to intensity-based fluorescence imaging this method is invariant to light scattering and absorption while being sensitive to the molecular composition of the tissue. They evaluated the feasibility of lifetime imaging of Protoporphyrin IX using the system to analyze brain tumor phantoms and fresh 5-ALA labeled human tissue samples. The results demonstrate the potential of this lifetime sensing device to go beyond the limitation of current intensity-based fluorescence-guided neurosurgery 2).

Books

Fluorescence-Guided Neurosurgery: Neuro-oncology and Cerebrovascular Applications September 10, 2018 The definitive textbook on state-of-the-art fluorescence-guided neurosurgery

Advances in fluorescence-guided surgery (FGS) have resulted in a paradigm shift in neurosurgical approaches to neuro-oncological and cerebrovascular pathologies. Edited by two of the foremost authorities on the topic, Fluorescence-Guided Neurosurgery: Neuro-oncology and Cerebrovascular Applications encompasses the depth and breadth of this groundbreaking, still nascent technology. The book reflects significant contributions made by world renowned neurosurgeons Constantinos Hadjipanayis, Walter Stummer, and esteemed contributors on the growing uses of 5-aminolevulinic acid (5-ALA) and other FGS agents.

The European Medicine Agency approved 5-ALA in 2007, heralding the birth of FGS globally. In 2017, the U.S. Food and Drug Administration approved 5-ALA (Gleolan) as an imaging agent to facilitate realtime detection and visualization of malignant tissue during glioma surgery. In the two decades since Dr. Stummer’s initial description of 5-ALA FGS in a human patient, major strides have been made in its practical applications, leading to improved resection outcomes. As FGS is increasingly incorporated into neurosurgical practice, it holds promise for future innovations. Generously-illustrated and enhanced with online videos, this textbook is the definitive resource on the subject.

Key Features

The improved efficacy of 5-ALA for resecting high- and low-grade gliomas, recurrences, meningiomas, brain metastases, spinal cord tumors, pediatric brain tumors, and other adult tumors The future of fluorescence, including potentially powerful new fluorophores molecularly targeted specifically to tumors The use of the fluorescent agent indocyanine green (ICG) for brain tumors, cerebral aneurysms, AVMs, and cerebral vascularization Special topics such as fluorescein, illuminating tumor paint, confocal microscopy, Raman spectroscopy, and integrating FGS with intraoperative imaging and brain mapping This single accessible reference presents the current state-of-the-art on this emerging, exciting surgical technology. As such, it is a must-have for neurosurgical residents, fellows, and practicing neurosurgeons.

1)

Moore GE, Peyton WT, French LA, Walker WW (1948) The clinical use of fluorescein in neurosurgery; the localization of brain tumors. J Neurosurg 5:392–398
2)

Erkkilä MT, Bauer B, Hecker-Denschlag N, Madera Medina MJ, Leitgeb RA, Unterhuber A, Gesperger J, Roetzer T, Hauger C, Drexler W, Widhalm G, Andreana M. Widefield fluorescence lifetime imaging of protoporphyrin IX for fluorescence-guided neurosurgery: an ex vivo feasibility study. J Biophotonics. 2019 Jan 12. doi: 10.1002/jbio.201800378. [Epub ahead of print] PubMed PMID: 30636030.
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