Multiple sclerosis related trigeminal neuralgia treatment

Multiple sclerosis related trigeminal neuralgia treatment

The optimal treatment for medically refractory trigeminal neuralgia in multiple sclerosis (MS-TN) patients is unknown.

Surgical interventions are less effective for the treatment of MS-related TN compared with classic TN, and higher recurrence rates are observed and is more difficult to manage pharmacologically.

Treatment failure occurs in most of the MS-related TN patients independently of the type of treatment.

Lee et al. compared treatment outcomes between stereotactic radiosurgery (SRS) and radiofrequency ablation (RFA).

They performed a retrospective study of MS-TN patients treated with SRS or RFA between 2002 and 2019. Outcomes included degree of pain relief, pain recurrence, and sensory changes, segregated based on initial treatment, final treatment following retreatment with the same modality, and crossover patients.

Sixty surgical cases for 42 MS-TN patients were reviewed. Initial pain freedom outcomes and rates of retreatment were similar (SRS: 30%; RFA: 42%). RFA resulted in faster onset of pain freedom (RFA: <1 week; SRS: 15 weeks; p < 0.001). SRS patients with pain relief had longer intervals to pain recurrence at 2 years (p = 0.044). Final treatment outcomes favored RFA for pain freedom/off-medication outcomes (RFA: 44%; SRS: 11%; p = 0.031), though RFA resulted in more paresthesia (RFA: 81%; SRS: 39%; p = 0.012). Both provided at least 80% of adequate pain relief. Crossover patients did not have improved pain relief.

SRS and RFA are both valid surgical options for MS-TN. Discussion with providers will need to balance patient preference with their unique treatment characteristics 1).

Microvascular decompression

see Microvascular decompression for trigeminal neuralgia and multiple sclerosis.

Gamma Knife surgery

Between July 1992 and November 2010, 43 cases with more than 1 year of follow-up were operated with GKS for TN related to MS and prospectively evaluated in the Timone University Hospital, Marseille, France. Radiosurgery using the Gamma Knife (model B or C or Perfexion) was performed. A single 4-mm isocenter was positioned at a median distance of 8 mm (range 5.7-14.7) anterior to the emergence of the nerve. A median maximum dose of 85 Gy (range 75-90) was delivered. Results: The median follow-up period was 53.8 months (12-157.1). Thirty-nine patients (90.7%) were initially pain free. Their actuarial probability of remaining pain free without medication at 6 months, 1, 3, 5 and 10 years was 87.2, 71.8, 43.1, 38.3 and 20.5%, respectively, and remained stable till 12 years. The hypoesthesia actuarial rate at 6 months, 1 and 2 years was 11.5, 11.5 and 16%, and remained stable till 12 years. GKS proved safe and effective in this special group of patients 2).

Balloon compression

see Percutaneous balloon compression trigeminal rhizotomy for multiple sclerosis related trigeminal neuralgia.

References

1)

Lee AT, Raygor KP, Elefant F, et al. Comparison of Stereotactic Radiosurgery and Radiofrequency Ablation for Trigeminal Neuralgia in Multiple Sclerosis Patients [published online ahead of print, 2020 Sep 3]. Stereotact Funct Neurosurg. 2020;1-8. doi:10.1159/000509315
2)

Tuleasca C, Carron R, Resseguier N, Donnet A, Roussel P, Gaudart J, Levivier M, Régis J. Multiple Sclerosis-Related Trigeminal Neuralgia: A Prospective Series of 43 Patients Treated with Gamma Knife Surgery with More than One Year of Follow-Up. Stereotact Funct Neurosurg. 2014 Jul 8;92(4):203-210. [Epub ahead of print] PubMed PMID: 25011487.

Medulloblastoma classification

Medulloblastoma classification

The diagnosis of medulloblastoma incorporates the histologic and molecular subclassification of clinical medulloblastoma samples into wingless (WNT)-activated, sonic hedgehog (SHH)-activated, group 3 and group 4 subgroups. Accurate medulloblastoma subclassification has important prognostic and treatment implications.

Medulloblastoma, WNT-activated

Medulloblastoma, WNT-activated

Sonic hedgehog medulloblastoma

Sonic hedgehog medulloblastoma.

Medulloblastoma, SHH-activated, and TP53-mutant

Medulloblastoma, SHH-activated, and TP53-mutant.

Medulloblastoma, SHH-activated, and TP53-wildtype

Medulloblastoma, SHH-activated, and TP53-wildtype

Medulloblastoma, non-WNT/non-SSH

Medulloblastoma non-WNT/non-SSH

Group 3 medulloblastoma

Group 3 medulloblastoma

Group 4 medulloblastoma

Group 4 medulloblastoma

Histology

Medulloblastoma histologically defined:

Classic medulloblastoma

Desmoplastic nodular medulloblastoma

Medulloblastoma with extensive nodularity

Medulloblastoma, large cell/anaplastic

Medulloblastoma, NOS.

Localization

see Cerebellar medulloblastomas

see Cerebellopontine angle medulloblastoma

see Multifocal medulloblastoma.

Subgrouping

Immunohistochemistry (IHC)-based and nanoString-based subgrouping methodologies have been independently described as options for medulloblastoma subgrouping, however, they have not previously been directly compared. D’Arcy described the experience with nanoString-based subgrouping in a clinical setting and compare this with our IHC-based results. Study materials included FFPE tissue from 160 medulloblastomas. Clinical data and tumor histology were reviewed. Immunohistochemical-based subgrouping using β-catenin, filamin A and p53 antibodies and nanoString-based gene expression profiling was performed. The sensitivity and specificity of IHC-based subgrouping of WNT and SHH-activated medulloblastomas was 91.5% and 99.54%, respectively. Filamin A immunopositivity highly correlated with SHH/WNT-activated subgroups (sensitivity 100%, specificity 92.7%, p < 0.001). Nuclear β-catenin immunopositivity had a sensitivity of 76.2% and specificity of 99.23% for the detection of WNT-activated tumors. Approximately 23.8% of WNT cases would have been missed using an IHC-based subgrouping method alone. nanoString could confidently predict medulloblastoma subgroup in 93% of cases and could distinguish group 3/4 subgroups in 96.3% of cases. nanoString-based subgrouping allows for a more prognostically useful classification of clinical medulloblastoma samples 1).


Molecular subgrouping was performed by immunohistochemistry (IHC) for beta catenin, GAB1 and YAP1; FISH for MYC amplification, and sequencing for CTNNB1, and by NanoString Assay on the same set of MBs. A subset of cases was subjected to 850k DNA methylation array.

IHC + FISH classified MBs into 15.8% WNT, 16.8% SHH, and 67.4% non-WNT/non-SHH subgroups; with MYC amplification identified in 20.3% cases of non-WNT/non-SHH. NanoString successfully classified 91.6% MBs into 25.3% WNT, 17.2% SHH, 23% Group 3 and 34.5% Group 4. However, NanoString assay failure was seen in eight cases, all of which were > 8-years-old formalin-fixed paraffin-embedded tissue blocks. Concordant subgroup assignment was noted in 88.5% cases, while subgroup switching was seen in 11.5% cases. Both methods showed prognostic correlation. Methylation profiling performed on discordant cases revealed 1 out of 4 extra WNT identified by NanoString to be WNT, others aligned with IHC subgroups; extra SHH by NanoString turned out to be SHH by methylation.

Both IHC supplemented by FISH and NanoString are robust methods for molecular subgrouping, albeit with few disadvantages. IHC cannot differentiate between Groups 3 and 4, while NanoString cannot classify older-archived tumors, and is not available at most centres. Thus, both the methods complement each other and can be used in concert for high confidence allotment of molecular subgroups in clinical practice 2).


The maturation of medulloblastoma into a ganglion cell-rich lesion is very rare, with few well-characterized previous reports. Given the rare nature of this entity, it would be of great value to understand the process of posttreatment maturation and the genetic and treatment factors which contribute to this phenomenon 3).

References

1)

D’Arcy CE, Nobre LF, Arnaldo A, Ramaswamy V, Taylor MD, Naz-Hazrati L, Hawkins CE. Immunohistochemical and nanoString-Based Subgrouping of Clinical Medulloblastoma Samples. J Neuropathol Exp Neurol. 2020 Jan 30. pii: nlaa005. doi: 10.1093/jnen/nlaa005. [Epub ahead of print] PubMed PMID: 32053195.
2)

Kaur K, Jha P, Pathak P, Suri V, Sharma MC, Garg A, Suri A, Sarkar C. Approach to molecular subgrouping of medulloblastomas: Comparison of NanoString nCounter assay versus combination of immunohistochemistry and fluorescence in-situ hybridization in resource constrained centres. J Neurooncol. 2019 May 18. doi: 10.1007/s11060-019-03187-y. [Epub ahead of print] PubMed PMID: 31104222.
3)

Mullarkey MP, Nehme G, Mohiuddin S, et al. Posttreatment Maturation of Medulloblastoma into Gangliocytoma: Report of 2 Cases [published online ahead of print, 2020 Sep 3]. Pediatr Neurosurg. 2020;1-10. doi:10.1159/000509520

Cerebrospinal fluid leak after endoscopic skull base surgery

Cerebrospinal fluid leak after endoscopic skull base surgery

Although rates of postoperative morbidity and mortality have become relatively low in patients undergoing transnasal transsphenoidal surgery (TSS) for pituitary adenomacerebrospinal fluid fistulas remain a major driver of postoperative morbidity. Persistent CSF fistulas harbor the potential for headache and meningitis.

Staartjes et al., trained and internally validated a robust deep neural network-based prediction model that identifies patients at high risk for intraoperative CSF. Machine learning algorithms may predict outcomes and adverse events that were previously nearly unpredictable, thus enabling safer and improved patient care and better patient counseling 1).


The objective of a study of Umamaheswaran et al., was to assess the incidence of CSF leak following pituitary surgery and the methods of effective skull base repair. This retrospective observational study conducted in a tertiary care hospital after obtaining due clearance from the Institutional ethics committee. The charts of patients who underwent endonasal pituitary surgery between 2013 and 2018 were studied and details noted. Patients undergoing revision surgery or with history of preoperative radiotherapy were excluded from the study. 52 patients were included in the study. Based on the type of CSF leak, the patients were grouped into four. 19 patients (36.5%) had an intraoperative CSF leak. 3 patients developed a postoperative CSF leak. Based on the histopathology, 4 patients had ACTH secreting tumor. 8 patients had growth hormone secreting tumor, 22 had gonadotropin secreting tumor, 9 patients had a non-functioning tumour and 9 patients had prolactinoma. The type of skull base repair performed in these patients were grouped into 4.18 patients underwent type I repair, 21 patients underwent type II repair, 8 patients underwent type III repair and 5 patients underwent type IV repair. They observed that the pedicled nasoseptal flap is particularly advantageous over other repair techniques, especially in low pressure leaks. The strategy for skull base repair should be tailored to suit each patient to minimise the occurrence of morbidity and the duration of hospital stay 2).


Cerebrospinal fluid leakage is always the primary complication during the endoscopic endonasal skull base surgery.

Dural suturing technique may supply a rescue method. However, suturing and knotting in such a deep and narrow space are difficult. Training in the model can improve skills and setting a stepwise curriculum can increase trainers’ interest and confidence.

Xie et al. constructed an easy model using silicone and acrylic as sphenoid sinus and using the egg-shell membrane as skull base dura. The training is divided into three steps: Step 1: extracorporeal knot-tying suture on the silicone of sphenoid sinus, Step 2: intra-nasal knot-tying suture on the same silicone, and Step 3: intra-nasal egg-shell membrane knot-tying suture. Fifteen experienced microneurosurgical neurosurgeons (Group A) and ten inexperienced PGY residents (Group B) were recruited to perform the tasks. Performance measures were time, suturing and knotting errors, and needle and thread manipulations. The third step was assessed through the injection of full water into the other side of the egg to verify the watertight suture. The results were compared between two groups.

Group A finishes the first and second tasks in significantly less time (total time, 125.1 ± 10.8 vs 195.8 ± 15.9 min) and fewer error points (2.4 ± 1.3 vs 5.3 ± 1.0) than group B. There are five trainers in group A who passed the third step, this number in group B was only one.

This low cost and stepwise training model improved the suture and knot skills for skull base repair during endoscopic endonasal surgery. Experienced microneurosurgical neurosurgeons perform this technique more competent 3).

In-Hospital Costs

All endoscopic transsphenoidal approach for pituitary surgeries performed from January 1, 2015, to October 24, 2017, with complete data were evaluated in a retrospective single-institution study. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables during each hospital stay. Multivariate linear regression was performed using Stata software.

The analysis included 190 patients and average length of stay was 4.71 days. Average total in-hospital cost was $28,624 (95% confidence interval $25,094-$32,155) with average total direct cost of $19,444 ($17,136-$21,752) and total indirect cost of $9181 ($7592-$10,409). On multivariate regression, post-operative cerebrospinal fluid (CSF) leak was associated with a significant increase in all cost variables, including a total cost increase of $40,981 ($15,474-$66,489, P = .002). Current smoking status was associated with an increased total cost of $20,189 ($6,638-$33,740, P = .004). Self-reported Caucasian ethnicity was associated with a significant decrease in total cost of $6646 (-$12,760 to -$532, P = .033). Post-operative DI was associated with increased costs across all variables that were not statistically significant.

Post-operative CSF leak, current smoking status, and non-Caucasian ethnicity were associated with significantly increased costs. Understanding of cost drivers of endoscopic transphenoidal pituitary surgery is critical for future cost control and value creation initiatives 4).

Case series

see Cerebrospinal fluid leak after endoscopic skull base surgery case series.

References

1)

Staartjes VE, Zattra CM, Akeret K, Maldaner N, Muscas G, Bas van Niftrik CH, Fierstra J, Regli L, Serra C. Neural network-based identification of patients at high risk for intraoperative cerebrospinal fluid leaks in endoscopic pituitary surgery. J Neurosurg. 2019 Jun 21:1-7. doi: 10.3171/2019.4.JNS19477. [Epub ahead of print] PubMed PMID: 31226693.
2)

Umamaheswaran P, Krishnaswamy V, Krishnamurthy G, Mohanty S. Outcomes of Surgical Repair of Skull Base Defects Following Endonasal Pituitary Surgery: A Retrospective Observational Study. Indian J Otolaryngol Head Neck Surg. 2019 Mar;71(1):66-70. doi: 10.1007/s12070-018-1511-4. Epub 2018 Oct 15. PubMed PMID: 30906716; PubMed Central PMCID: PMC6401034.
3)

Xie T, Zhang X, Gu Y, Sun C, Liu T. A low cost and stepwise training model for skull base repair using a suturing and knotting technique during endoscopic endonasal surgery. Eur Arch Otorhinolaryngol. 2018 Jun 1. doi: 10.1007/s00405-018-5024-2. [Epub ahead of print] PubMed PMID: 29858924.
4)

Parasher AK, Lerner DK, Glicksman JT, et al. Drivers of In-Hospital Costs Following Endoscopic Transphenoidal Pituitary Surgery [published online ahead of print, 2020 Aug 24]. Laryngoscope. 2020;10.1002/lary.29041. doi:10.1002/lary.29041
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