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.

Traumatic spinal cord injury treatment

Early decompression surgery post-SCI can enhance patient outcomes, but does not directly facilitate neural repair and regeneration. Currently, there are no U.S. Food and Drug Administration-approved pharmacological therapies to augment motor function and functional recovery in individuals with traumatic SCI.

Acute traumatic spinal cord injury (SCI) is a devastating event with far-reaching physical, emotional, and economic consequences for patients, families, and society at large. Timely delivery of specialized care has reduced mortality; however, long-term neurological recovery continues to be limited. In recent years, a number of exciting neuroprotective and regenerative strategies have emerged and have come under active investigation in clinical trials, and several more are coming down the translational pipeline. Among ongoing trials are RISCIS (riluzole), INSPIRE study (Neuro-Spinal Scaffold), MASC (minocycline), and SPRING (VX-210). Microstructural MRI techniques have improved our ability to image the injured spinal cord at high resolution. This innovation, combined with serum and cerebrospinal fluid (CSF) analysis, holds the promise of providing a quantitative biomarker readout of spinal cord neural tissue injury, which may improve prognostication and facilitate stratification of patients for enrollment into clinical trials. Given evidence of the effectiveness of early surgical decompression and growing recognition of the concept that “time is spine,” infrastructural changes at a systems level are being implemented in many regions around the world to provide a streamlined process for transfer of patients with acute SCI to a specialized unit. With the continued aging of the population, central cord syndrome is soon expected to become the most common form of acute traumatic SCI; characterization of the pathophysiologynatural history, and optimal treatment of these injuries is hence a key public health priority. Collaborative international efforts have led to the development of clinical practice guidelines for traumatic SCI based on robust evaluation of current evidence 1).

1)

Badhiwala JH, Ahuja CS, Fehlings MG. Time is spine: a review of translational advances in spinal cord injury. J Neurosurg Spine. 2018 Dec 20;30(1):1-18. doi: 10.3171/2018.9.SPINE18682. Review. PubMed PMID: 30611186.

Unruptured intracranial aneurysm endovascular treatment

There is no randomized data available to compare the results of surgery versus endovascular treatment of unruptured aneurysms (UIAs) 1).

Unruptured intracranial aneurysm endovascular treatment can be performed with relative safety. The long-term follow-up results of unruptured intracranial aneurysm treatment (UIAs) by means of coil embolization remain unclear.

The efficacy of treatment as compared with observation has not been rigorously documented 2).

The use of coiling relative to surgical clipping of unruptured intracranial aneurysms is associated with decreasing periprocedural morbidity and mortality among patients treated in the United States from 2001 to 2008 3).


Koyanagi et al., from the National Hospital Organization Himeji Medical CenterKyoto University Graduate School of Medicine, Kobe City Medical Center General Hospital, National Cerebral and Cardiovascular Center, Suita and Kokura Memorial Hospital Japan.

retrospectively analyzed data from cases in which patients underwent coil embolization between 1995 and 2004 at 4 stroke centers. In collecting the late (≥ 1 year) follow-up data, postal questionnaires were used to assess whether patients had experienced rupture or retreatment of a coiled aneurysm or any stroke or had died.

Overall, 184 patients with 188 UIAs were included. The median follow-up period was 12 years (interquartile range 11-13 years, maximum 20 years). A total of 152 UIAs (81%) were followed for more than 10 years. The incidence of rupture was 2 in 2122 aneurysm-years (annual rupture rate 0.09%). Nine of the 188 patients with coiled UIAs (4.8%) underwent additional treatment. In 5 of these 9 cases, the first retreatment was performed more than 5 years after the initial treatment. Large aneurysms were significantly more likely to require retreatment. Nine strokes occurred over the 2122 aneurysm-years. Seventeen patients died in this cohort.

This study demonstrates a low risk of rupture of coiled UIAs with long-term follow-up periods of up to 20 years. This suggests that coiling of UIAs could prevent rupture for a long period of time. However, large aneurysms might need to be followed for a longer time 4).


Bekelis et al., investigated the association of combined open and endovascular expertise with the outcomes of unruptured cerebral aneurysm coiling.

Bekelis et al., performed a cohort study of 100% of Medicare fee-for-service claims data for elderly patients who underwent endovascular coiling for unruptured cerebral aneurysms between 2007 and 2012. To control for confounding, the authors used propensity score conditioning, with mixed effects to account for clustering at the hospital referral region level.

During the study period, there were 11,716 patients who underwent endovascular coiling for unruptured cerebral aneurysms and met the inclusion criteria. Of these, 1186 (10.1%) underwent treatment performed by hybrid neurosurgeons, and 10,530 (89.9%) by proceduralists who performed only endovascular coiling. Multivariable regression analysis with propensity score adjustment demonstrated a lack of association of combined practice with 1-year postoperative mortality (OR 0.84; 95% CI 0.58-1.23), discharge to rehabilitation (OR 1.0; 95% CI 0.66-1.51), 30-day readmission rate (OR 1.07; 95% CI 0.83-1.38), and length of stay (adjusted difference, 0.41; 95% CI -0.26 to 1.09). Higher procedural volume was independently associated with improved outcomes.

In a cohort of Medicare patients, the authors did not demonstrate a difference in mortality, discharge to rehabilitation, readmission rate, and LOS between hybrid neurosurgeons and proceduralists performing only endovascular coiling 5) .


A portfolio of 41 cases of unruptured intracranial aneurysms with angiographic images, along with a short description of the patient presentation, was sent to 28 clinicians (16 radiologists and 12 surgeons) with varying years of experience in the management of unruptured intracranial aneurysms. Five senior clinicians responded twice at least 3 months apart. Nineteen cases (46%) were selected from patients recruited in the Canadian UnRuptured Endovascular versus Surgery trial, an ongoing randomized comparison of coil embolization and clip placement. For each case, the responder was to first choose between 3 treatment options (observation, surgical clip placement, or endovascular coil embolization) and then indicate their level of certainty on a quantitative 0-10 scale. Agreement in decision making was studied using κ statistics.

Decisions to coil were more frequent (n = 612, 53%) than decisions to clip (n = 289, 25%) or to observe (n = 259, 22%). Interjudge agreement was only fair (κ = 0.31 ± 0.02) for all cases and all judges, despite substantial intrajudge agreement (range 0.44-0.83 ± 0.10), with high mean individual certainty levels for each case (range 6.5-9.4 ± 2.0 on a scale of 0-10). Agreement was no better within specialties (surgeons or radiologists), within capability groups (those able to perform endovascular coiling alone, surgical clipping alone, or both), or with more experience. There was no correlation between certainty levels and years of experience. Agreement was lower when the cases were taken from the randomized trial (κ = 0.19 ± 0.2) compared with nontrial cases (κ = 0.35 ± 0.2).

Individuals do not agree regarding the management of unruptured intracranial aneurysms, even when they share a background in the same specialty, similar capabilities in aneurysm management, or years of practice. If community equipoise is a necessary precondition for trial participation, this study has found sufficient uncertainty and disagreement among clinicians to justify randomized trials 6).

For unruptured cerebral aneurysms, an observed perioperative survival advantage for endovascular coiling relative to that for surgical clipping was lost on long-term follow-up, according to data from an administrative database of patients who were not randomly allocated to treatment type. A cost advantage of endovascular treatment was maintained even though endovascularly treated patients were more likely to undergo subsequent hospitalizations for additional aneurysm repair procedures. Rates of aneurysm rupture following treatment were similar in the two groups 7).


Diffusion-weighted MR images (DWI) obtained after endovascular treatment of cerebral aneurysms frequently show multiple high-signal intensity (HSI) dots.

Aspiration of the inner content of the microcatheter right after detachable coil delivery was helpful for the reduction of the incidence of microembolisms after endovascular coil embolization for the treatment of unruptured cerebral aneurysms 8).

References

1)

Darsaut TE, Findlay JM, Raymond J; CURES Collaborative Group. The design of the Canadian UnRuptured Endovascular versus Surgery (CURES) trial. Can J Neurol Sci. 2011 Mar;38(2):236-41. PubMed PMID: 21320826; PubMed Central PMCID: PMC3528784.
2)

Naggara ON, White PM, Guilbert F, Roy D, Weill A, Raymond J. Endovascular treatment of intracranial unruptured aneurysms: systematic review and meta-analysis of the literature on safety and efficacy. Radiology. 2010 Sep;256(3):887-97. doi: 10.1148/radiol.10091982. Epub 2010 Jul 15. Review. PubMed PMID: 20634431.
3)

Brinjikji W, Rabinstein AA, Nasr DM, Lanzino G, Kallmes DF, Cloft HJ. Better outcomes with treatment by coiling relative to clipping of unruptured intracranial aneurysms in the United States, 2001-2008. AJNR Am J Neuroradiol. 2011 Jun-Jul;32(6):1071-5. doi: 10.3174/ajnr.A2453. Epub 2011 Apr 21. PubMed PMID: 21511860.
4)

Koyanagi M, Ishii A, Imamura H, Satow T, Yoshida K, Hasegawa H, Kikuchi T, Takenobu Y, Ando M, Takahashi JC, Nakahara I, Sakai N, Miyamoto S. Long-term outcomes of coil embolization of unruptured intracranial aneurysms. J Neurosurg. 2018 Jan 5:1-7. doi: 10.3171/2017.6.JNS17174. [Epub ahead of print] PubMed PMID: 29303448.
5)

Bekelis K, Gottlieb D, Labropoulos N, Su Y, Tjoumakaris S, Jabbour P, MacKenzie TA. The impact of hybrid neurosurgeons on the outcomes of endovascular coiling for unruptured cerebral aneurysms. J Neurosurg. 2016 Feb 26:1-7. [Epub ahead of print] PubMed PMID: 26918479.
6)

Darsaut TE, Estrade L, Jamali S, Bojanowski MW, Chagnon M, Raymond J. Uncertainty and agreement in the management of unruptured intracranial aneurysms. J Neurosurg. 2014 Jan 3. [Epub ahead of print] PubMed PMID: 24405069.
7)

Gonda DD, Khalessi AA, McCutcheon BA, Marcus LP, Noorbakhsh A, Chen CC, Chang DC, Carter BS. Long-term follow-up of unruptured intracranial aneurysms repaired in California. J Neurosurg. 2014 Jun;120(6):1349-57. doi: 10.3171/2014.3.JNS131159. Epub 2014 Apr 11. PubMed PMID: 24724850.
8)

Kim DY, Park JC, Kim JK, Sung YS, Park ES, Kwak JH, Choi CG, Lee DH. Microembolism after Endovascular Treatment of Unruptured Cerebral Aneurysms: Reduction of its Incidence by Microcatheter Lumen Aspiration. Neurointervention. 2015 Sep;10(2):67-73. doi: 10.5469/neuroint.2015.10.2.67. Epub 2015 Sep 2. PubMed PMID: 26389009.

Flow Diversion for the Treatment of Basilar Bifurcation Aneurysm

Flow diversion for basilar apex aneurysms has rarely been reported.

A retrospective review of prospectively maintained databases at 8 academic institutions (St. Michael’s Hospital, Toronto, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.Toronto Western Hospital, University of Alabama at Birmingham, State University of New York at Buffalo, University of Florence, Italy. Toulouse University Hospital, Yale School of Medicine, New Haven), was performed from 2009 to 2016 to identify patients with basilar apex aneurysms treated with flow diversion. Clinical and radiographic data were analyzed.

Sixteen consecutive patients (median age 54.5 yr) underwent 18 procedures to treat 16 basilar apex aneurysms with either the Pipeline Embolization Device (Medtronic) or Flow Redirection Endoluminal Device (Microvention). Five aneurysms (31.3%) were treated in the setting of subarachnoid hemorrhage. Seven aneurysms (43.8%) were treated with flow diversion alone, while 9 (56.2%) underwent flow diversion and adjunctive coiling. At a median follow-up of 6 mo, complete (100%) and near-complete (90%-99%) occlusion was noted in 11 (68.8%) aneurysms. Incomplete occlusion occurred more commonly in patients treated with flow diversion alone compared to those with adjunctive coiling. Patients with partial occlusion were significantly younger. Retreatment with an additional flow diverter and adjunctive coiling occurred in 2 wide necked aneurysms. There was 1 mortality in a patient (6.3%) who experienced posterior cerebral artery and cerebellar strokes as well as subarachnoid hemorrhage after the placement of a flow diverter. Minor complications occurred in 2 patients (12.5%).

Flow diversion for the treatment of basilar apex aneurysms results in acceptable occlusion rates in highly selected cases. Both primary flow diversion and rescue after failed clipping or coiling resulted in a modified Rankin Scale score that was either equal or better than at presentation and the technology represents a viable alternative or adjunctive option 1).


Da Ros et al., retrospectively analyzed data from all consecutive patients treated with flow-diverter stents between January 2011 and January 2015. Patients with large basilar apex aneurysms treated with a flow-diverter stent were included in the study. Clinical presentations, technical details, intra- and perioperative complications, and clinical and angiographic outcomes were recorded, with a midterm follow-up.

Of the 175 aneurysms treated with flow-diverter stents, 5 patients (2 women and 3 men; age range, 44-58 years) received flow-diverter stent for basilar apex aneurysms. The mean follow-up after stent deployment was 21 months (range, 15-24 months). One patient died on day 31 from an early postprocedural midbrain hemorrhage. One patient had a right cerebellar hemispheric ischemic lesion with a transient cerebellar syndrome resolved within 24 hours without neurologic sequelae at the latest follow-up. The mRS was 0 in 4 patients and 6 in 1 patient at last follow-up.

Flow diversion is a feasible technique with an efficacy demonstrated at a midterm follow-up, especially in the case of basilar apex aneurysm recurrences after previous endovascular treatments. Concern about its safety profile still exists 2).


A 73-year-old male was previously treated for an unruptured 11-mm basilar apex aneurysm with stent-assisted coiling using a Neuroform stent. The aneurysm was retreated twice with repeat coiling. After the third recurrence and persistent aneurysm growth into a giant, symptomatic lesion, we decided to proceed with flow diversion. We performed Y-stenting of the basilar bifurcation using three PFEDs, and was recoiled the aneurysm sac. Due to the low porosity of the flow diverters, a side-by-side double-barrel configuration was necessary in the basilar artery. Without the PFED’s resheathable capability, it would not have been possible to perform Y-stenting with flow diverters 3).

References

1)

Dmytriw AA, Adeeb N, Kumar A, Griessenauer CJ, Phan K, Ogilvy CS, Foreman PM, Shallwani H, Limbucci N, Mangiafico S, Michelozzi C, Krings T, Pereira VM, Matouk CC, Zhang Y, Harrigan MR, Shakir HJ, Siddiqui AH, Levy EI, Renieri L, Cognard C, Thomas AJ, Marotta TR. Flow Diversion for the Treatment of Basilar Apex Aneurysms. Neurosurgery. 2018 Dec 1;83(6):1298-1305. doi: 10.1093/neuros/nyx628. PubMed PMID: 29529233.
2)

Da Ros V, Caroff J, Rouchaud A, Mihalea C, Ikka L, Moret J, Spelle L. Large Basilar Apex Aneurysms Treated with Flow-Diverter Stents. AJNR Am J Neuroradiol. 2017 Jun;38(6):1156-1162. doi: 10.3174/ajnr.A5167. Epub 2017 Apr 27. PubMed PMID: 28450438.
3)

Ding D, Starke RM, McGuinness B, Brew S. Double-barrel Y-configuration Stenting for Flow Diversion of a Giant Recurrent Basilar Apex Aneurysm with the Pipeline Flex Embolization Device. J Neurosci Rural Pract. 2016 Dec;7(Suppl 1):S99-S102. doi: 10.4103/0976-3147.196439. PubMed PMID: 28163518; PubMed Central PMCID: PMC5244076.

Diffuse axonal injury treatment

The National Institute of Neurological Disorders and Stroke hosted a workshop in May 2011. This workshop sought to determine what is known regarding the pathogenesis of DAI in animal models of injury as well as in the human clinical setting. The workshop also addressed new tools to aid in the identification of this axonal injury while also identifying more rational therapeutic targets linked to DAI for continued preclinical investigation and, ultimately, clinical translation. This report encapsulates the oral and written components of this workshop addressing key features regarding the pathobiology of DAI, the biomechanics implicated in its initiating pathology, and those experimental animal modeling considerations that bear relevance to the biomechanical features of human TBI. Parallel considerations of alternate forms of DAI detection including, but not limited to, advanced neuroimaging, electrophysiological, biomarker, and neurobehavioral evaluations are included, together with recommendations for how these technologies can be better used and integrated for a more comprehensive appreciation of the pathobiology of DAI and its overall structural and functional implications. Lastly, the document closes with a thorough review of the targets linked to the pathogenesis of DAI, while also presenting a detailed report of those target-based therapies that have been used, to date, with a consideration of their overall implications for future preclinical discovery and subsequent translation to the clinic. Although all participants realize that various research gaps remained in our understanding and treatment of this complex component of TBI, this workshop refines these issues providing, for the first time, a comprehensive appreciation of what has been done and what critical needs remain unfulfilled 1).


Treatment of patients with diffuse axonal injury are geared toward prevention of secondary injuries and facilitating rehabilitation. It appears to be the secondary injuries that lead to increased mortality. These can include hypoxia with coexistent hypotension, edema, and intracranial hypertension. Therefore, prompt care to avoid hypotension, hypoxia, cerebral edema, and elevated intracranial pressure (ICP) is advised.

Initial treatment priority in traumatic brain injury is focused on resuscitation. In a non-neuro trauma center, trauma surgeons and emergency physicians may perform the initial resuscitation and neurologic treatment to stabilize and transport the patient to a designated neurotrauma center expeditiously. ICP monitoring is indicated in patients with GCS of less than 8 after consultation with neurosurgery. Other considerations for ICP monitoring include patients that cannot have continual neurologic evaluations. These are typically in patients receiving general anesthesia, narcotic analgesia, sedation, and prolonged paralysis for other injuries. Cerebral oxygen saturation monitoring can be used with ICP monitoring to assess the degree of oxygenation. Short-term, usually seven days, anticonvulsant treatment can be used to prevent early post-traumatic seizures. There is no evidence that this will prevent long-term post-traumatic seizures however. There is emerging evidence that progesterone treatment in acute traumatic brain injury may reduce morbidity and mortality. This cannot be routinely recommended at this time.

Overall, the goal of diffuse axonal injury patients’ treatment is supportive care and prevention of secondary injuries 2).


Immediate measures will be taken to reduce swelling inside the brain, which can cause additional damage. In most cases, a course of steroids or other medications designed to reduce inflammation and swelling will be administered, and the patient will be monitored.


Findings of a study suggest that progesterone may be neuroprotective in patients with DAI. However, large clinical trials are needed to assess progesterone as a promising drug in DAI 3).


Diffuse axonal injury (DAI) patients are frequently accompanied by adverse sequelae and psychiatric disorders, such as anxiety, leading to a decreased quality of life, social isolation, and poor outcomes. However, the mechanisms regulating psychiatric disorders post-DAI are not well elucidated. Previous studies showed that endoplasmic reticulum stress functions as a pivotal factor in neurodegeneration disease. In a study, Huang et al., showed that DAI can trigger ER stress and unfolded protein response (UPR) activation in both the acute and chronic periods, leading to cell death and anxiety disorder. Treatment with 4-phenylbutyrate (4-PBA) is able to inhibit the UPR and cell apoptosis and relieve the anxiety disorder in our DAI model. However, later (14 days post-DAI) 4-PBA treatment can only restore the related gene expression of ER stress and UPR but not the psychiatric disorder. Therefore, the early (5 mins after DAI) administration of 4-PBA might be a therapeutic approach for blocking the ER stress/UPR-induced cell death and anxiety disorder after DAI 4).

Surgery

Surgery is not an option for those who have sustained a diffuse axonal injury.

Rehabilitation

If the patient has sustained a mild or moderate diffuse axonal injury, the rehabilitation phase will follow once the patient is stabilized and awake.

During this phase of treatment, the patient and his or her family will work with a multidisciplinary staff including doctors, nurses, physical and occupational therapists, and other specialists to devise an individualized program designed to return the patient to the maximum level of function. The rehabilitation phase may include:

Speech therapy

Physical therapy

Occupational therapy

Recreational therapy

Adaptive equipment training

Counseling

References

1)

Smith DH, Hicks R, Povlishock JT. Therapy development for diffuse axonal injury. J Neurotrauma. 2013 Mar 1;30(5):307-23. doi: 10.1089/neu.2012.2825. Epub 2013 Feb 14. PubMed PMID: 23252624; PubMed Central PMCID: PMC3627407.
2)

Mesfin FB, Taylor RS. Diffuse Axonal Injury (DAI). 2018 Dec 2. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK448102/ PubMed PMID: 28846342.
3)

Soltani Z, Shahrokhi N, Karamouzian S, Khaksari M, Mofid B, Nakhaee N, Reihani H. Does progesterone improve outcome in diffuse axonal injury? Brain Inj. 2016 Nov 7:1-8. [Epub ahead of print] PubMed PMID: 27819489.
4)

Huang GH, Chen K, Sun YY, Zhu L, Sun ZL, Feng DF. 4-Phenylbutyrate ameliorates anxiety disorder by inhibiting endoplasmic reticulum stress following diffuse axonal injury. J Neurotrauma. 2018 Dec 22. doi: 10.1089/neu.2018.6048. [Epub ahead of print] PubMed PMID: 30582423.

Unruptured intracranial aneurysm treatment decision

For a treatment decision of unruptured intracranial aneurysmphysicians and patients need to weigh the risk of treatment against the risk of hemorrhagic stroke caused by aneurysm rupture.

In a study of Detmer et al. Image segmentation data and patient information obtained from two patient cohorts including 203 patients with 249 aneurysms were used for patient-specific computational fluid dynamics simulations and subsequent evaluation of the statistical model in terms of accuracydiscrimination, and goodness of fit. The model’s performance was further compared to a similarity-based approach for rupture assessment by identifying aneurysms in the training cohort that were similar in terms of intracranial aneurysm hemodynamics and shape compared to a given aneurysm from the external cohorts.

When applied to the external data, the model achieved a good discrimination and goodness of fit (area under the receiver operating characteristic curve AUC = 0.82), which was only slightly reduced compared to the optimism-corrected AUC in the training population (AUC = 0.84). The accuracy metrics indicated a small decrease in accuracy compared to the training data (misclassification error of 0.24 vs. 0.21). The model’s prediction accuracy was improved when combined with the similarity approach (misclassification error of 0.14).

The model’s performance measures indicated a good generalizability for data acquired at different clinical institutions. Combining the model-based and similarity-based approach could further improve the assessment and interpretation of new cases, demonstrating its potential use for clinical unruptured intracranial aneurysm rupture risk assessment 1).

Scores

see also Unruptured intracranial aneurysm treatment score.

Unruptured intracranial aneurysm repair is the most commonly performed procedure for the prevention of hemorrhagic stroke. Despite efforts to regionalize care in high-volume centers, overall results have improved little 2).

The management of small unruptured incidentally discovered intracranial aneurysms (SUIAs) is still controversial.

Despite large trials supporting the management of small asymptomatic aneurysms, most neurosurgeons internationally chooses to treat them with surgery or endovascular means. Since clinicians use a number of factors beyond the maximum diameter when considering treatment options, future trials should consider these factors in their design 3).

Once a decision has been made to treat an intact aneurysm, the best treatment remains uncertain. Both surgical and endovascular management strategies are commonly performed for these lesions.

No one knows how best to manage these patients (an estimated 2—5% of the adult population), but with the increasing accessibility of non-invasive imaging, physicians are increasingly faced with the dilemma of what to do 4).

One stance maintains that the only acceptable rationale for a preventive treatment is randomised evidence that therapy does more good than harm. Thus, a randomised trial showing better outcomes for treated patients compared with conservatively managed patients would be necessary to justify invasive treatment of UIAs. However, this trial has not yet been successfully completed.

Posterior circulation in surgery, large aneurysms (>15 mm) in EVT, and stent- or balloon-assisted procedures in EVT were associated with the occurrence of complications. Poor clinical outcome (mRS of 3-6) was 0.8 % at hospital discharge.1) Detmer FJ, Fajardo-Jiménez D, Mut F, Juchler N, Hirsch S, Pereira VM, Bijlenga P, Cebral JR. External validation of cerebral aneurysm rupture probability model with data from two patient cohorts. Acta Neurochir (Wien). 2018 Dec;160(12):2425-2434. doi: 10.1007/s00701-018-3712-8. Epub 2018 Oct 30. PubMed PMID: 30374656.2) Zacharia BE, Bruce SS, Carpenter AM, Hickman ZL, Vaughan KA, Richards C, Gold WE, Lu J, Appelboom G, Solomon RA, Connolly ES. Variability in outcome after elective cerebral aneurysm repair in high-volume academic medical centers. Stroke. 2014 May;45(5):1447-52. doi: 10.1161/STROKEAHA.113.004412. Epub 2014 Mar 25. PubMed PMID: 24668204.3) Alshafai N, Falenchuk O, Cusimano MD. Practises and controversies in the management of asymptomatic aneurysms: Results of an international survey. Br J Neurosurg. 2015 Nov 5:1-7. [Epub ahead of print] PubMed PMID: 26540183.4) Raymond J, Darsaut TE, Molyneux AJ. A trial on unruptured intracranial aneurysms (the TEAM trial): results, lessons from a failure and the necessity for clinical care trials. Trials 2011; 12: 64.

Medically refractory trigeminal neuralgia treatment

see Trends in surgical treatment for trigeminal neuralgia

see Cost effectiveness in surgical treatment for trigeminal neuralgia.

Microvascular decompression

see Microvascular decompression for trigeminal neuralgia

Percutaneous procedures

see Percutaneous trigeminal rhizotomy.

Gamma Knife radiosurgery

see Gamma Knife radiosurgery for trigeminal neuralgia.


Microvascular decompression should be performed more prudently in elderly patients (>80 years old), and the indications for PR should be relatively relaxed. MVD + PR could improve the curative effect in patients with trigeminal neuralgia >80 years. Gamma knife treatment of trigeminal neuralgia had high safety, less complications, and positive curative effect, especially suitable for patients >80 years 1).


MVD results in superior rates of short- and long-term pain relief, facial numbness and dysesthesia control, and less recurrence amongst those in whom pain freedom was achieved, at the cost of greater postoperative complications when compared to SRS. Although no significant difference was found in terms of the need for retreatment surgery, there was a trend towards less procedures favoring MVD. First treatment by either technique represents the overall trends reported 2).

References

1) Yu R, Wang C, Qu C, Jiang J, Meng Q, Wang J, Wei S. Study on the Therapeutic Effects of Trigeminal Neuralgia With Microvascular Decompression and Stereotactic Gamma Knife Surgery in the Elderly. J Craniofac Surg. 2018 Nov 30. doi: 10.1097/SCS.0000000000004999. [Epub ahead of print] PubMed PMID: 30507874. 2) Lu VM, Duvall JB, Phan K, Jonker BP. First treatment and retreatment of medically refractive trigeminal neuralgia by stereotactic radiosurgery versus microvascular decompression: a systematic review and Meta-analysis. Br J Neurosurg. 2018 May 10:1-10. doi: 10.1080/02688697.2018.1472213. [Epub ahead of print] PubMed PMID: 29745268.

Update: Antiepileptic drug treatment outcome

Antiepileptic drug treatment outcome

Careful antiepileptic drug selection for epileptic patients must be highlighted in order to improve outcome, reduce adverse drug reactions (ADRs) and improve patient compliance 1).
The goal in treating patients with epilepsy is a cost-effective approach to the elimination of seizures or a reduction in their number and frequency while avoiding drug interactions and side effects, so as to achieve the best possible quality of life. Among the desirable outcomes are an enhanced understanding of epilepsy by patients, caregivers, and society, and a lessening of the psychosocial risks of this disease. Patients fail to achieve their goals and outcomes when they fail to adhere to the drug regimen or when a less-than-adequate drug regimen is prescribed. To help improve adherence, once- or twice-daily formulations should be used. Working together, patients and clinicians can maximize the effectiveness of AED therapy and the potential for achieving desired goals and outcomes 2).
Despite the availability of many new AEDs with differing mechanisms of action, overall outcomes in newly diagnosed epilepsy have not improved. Most patients who attain control do so with the first or second AED. The probability of achieving seizure freedom diminishes substantially with each subsequent AED regimen tried. More than one-third of patients experience epilepsy that remains uncontrolled.
This was the conclusion of a longitudinal observational cohort study that was conducted at the Epilepsy Unit of the Western Infirmary in GlasgowScotland. A total of 1795 individuals who were newly treated for epilepsy with AEDs between July 1, 1982, and October 31, 2012, were included in this analysis. All patients were followed up for a minimum of 2 years (until October 31, 2014) or until death, whichever came sooner. Data analysis was completed between March 2015 and May 2016.
Seizure control was assessed at the end of the study period. Probability of achieving 1-year seizure freedom was estimated for each AED regimen prescribed. Multivariable models assessed the associations between risk factors and AED treatment outcome after adjustments were made for demographic and clinical characteristics.
Of the 1795 included patients, 964 (53.7%) were male; the median age was 33 years (range, 9-93 years). At the end of the study period, 1144 patients (63.7%) had been seizure free for the previous year or longer. Among those achieving 1-year seizure freedom, 993 (86.8%) were taking monotherapy and 1028 (89.9%) had achieved seizure control with the first or second AED regimens. Of the total patient pool, 906 (50.5%) remained seizure free for 1 year or longer with the initial AED. If this AED failed, the second and third regimens provided an additional 11.6% and 4.4% likelihoods of seizure freedom, respectively. Only 2.12% of patients attained optimal seizure control with subsequent AEDs. Epilepsy that was not successfully controlled with the first AED had 1.73 times greater odds of not responding to treatment for each subsequent medication regimen (odds ratio, 1.73; 95% CI, 1.56-1.91; P < .001). 3).


Machine learning approaches yielded predictions of successful drug treatment outcomes which in turn could reduce the burdens of drug trials and lead to substantial improvements in patient quality of life 4).
1)

Horváth L, Fekete K, Márton S, Fekete I. Outcome of antiepileptic drug treatment of 1282 patients with epilepsy, their pharmacovigilance reports and concomitant medication on CNS in an East-Hungarian adult database. J Neurol Sci. 2016 Oct 15;369:220-226. doi: 10.1016/j.jns.2016.08.039. Epub 2016 Aug 17. PubMed PMID: 27653893.
2)

Garnett WR. Antiepileptic drug treatment: outcomes and adherence. Pharmacotherapy. 2000 Aug;20(8 Pt 2):191S-199S. Review. PubMed PMID: 10937819.
3)

Chen Z, Brodie MJ, Liew D, Kwan P. Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs: A 30-Year Longitudinal Cohort Study. JAMA Neurol. 2018 Mar 1;75(3):279-286. doi: 10.1001/jamaneurol.2017.3949. PubMed PMID: 29279892; PubMed Central PMCID: PMC5885858.
4)

Colic S, Wither RG, Lang M, Zhang L, Eubanks JH, Bardakjian BL. Prediction of antiepileptic drug treatment outcomes using machine learning. J Neural Eng. 2017 Feb;14(1):016002. doi: 10.1088/1741-2560/14/1/016002. Epub 2016 Nov 30. PubMed PMID: 27900948.

Why Me?: My 8-year treatment journey For Hemifacial Spasm (tic convulsif)

Why Me?: My 8-year treatment journey For Hemifacial Spasm (tic convulsif)


List Price : $4.99
ADD TO SHOPPING CART
Hemifacial spasm is a neuromuscular movement disorder characterized by brief or persistent involuntary contractions of the muscles innervated by the facial nerve. Its prevalence has been estimated at 11 cases per 100,000 individuals.
Hemifacial spasm is usually caused by an artery compressing the facial nerve at the root exit zone of the brainstem. As for treatment, many  patients obtain moderate or marked relief from local injections of botulinum toxin (Botox), which must be repeated every 3 to 4 months. Alternatively, microvascular decompression has a success rate of about 85%.

My story follows my more than 8 year struggle with this condition and is written to hopefully help those who are going through the same thing to a positive and successful treatment.

 

WhatsApp WhatsApp us
%d bloggers like this: