Peripheral Nerve

NFTI-QOL

NFTI-QOL

The NFTI-QOL is a robustly constructed disease-specific QOL questionnaire for neurofibromatosis type 2. It correlates strongly and significantly with EuroQOL and all SF-36 domains (p < 0.01). It is straightforward and quick (≤3 minutes) for patients to complete and easy to score. It is suitable as a quantitative method of assessing QOL in NF2 both in a clinical setting and as an outcome measure for treatment. The NFTI-QOL has been validated for adults (>16 years) in the United Kingdom, and could be adapted for use in other countries 1).

The aim of the study of Lawson McLean et al was to produce and validate a German version of the NFTI-QOL (NFTI-QOL-D) and to correlate QOL scores with a depression score (PHQ-9) and clinical disease severity.

The original English-language NFTI-QOL was translated into German and then back-translated in order to preserve the questionnaire’s original concepts and intentions. A link to an online survey encompassing the NFTI-QOL-D and the PHQ-9 depression questionnaire was then sent to 97 patients with NF2 by email. The respondents’ scores were compared to clinician-reported disease severity scores.

77 patients completed the online survey in full. Internal consistency among NFTI-QOL-D responses was strong (Cronbach’s alpha: 0.74). Both PHQ-9 and clinician disease severity scores correlated with NFTI-QOL-D scores (Pearson correlation coefficient rho 0.63 and 0.62, respectively).

The NFTI-QOL-D is a reliable and useful tool to assess patient-reported QOL in German-speaking patients with neurofibromatosis type 2. The correlation of QOL with both psychological and physical disease parameters underlines the importance of individualized interdisciplinary patient care for NF2 patients, with attention paid to mental well-being as well as to somatic disease manifestations 2).

Case series

Data were evaluated for 288 NF2 patients (n = 464 visits) attending the English national NF2 clinics from 2010 to 2012. The male-to-female ratio was equal and the mean age was 42.2 (SD 17.8) years. The analysis included NFTI-QOL eight-item score, ClinSev graded as mild, moderate, or severe, and GenSev as a rank order of the number of NF2 mutations (graded as mild, moderate, severe). The mean (SD) 8.7 (5.4) score for NFTI-QOL for either a first visit or all visits 9.2 (5.4) was similar to the published norm of 9.4 (5.5), with no significant relationships with age or gender. NFTI-QOL internal reliability was good, with a Cronbach’s alpha score of 0.85 and test re-test reliability r = 0.84. NFTI related to ClinSev (r = 0.41, p < 0.001; r = 0.46 for all visits), but weakly to GenSev (r = 0.16, p < 0.05; r = 0.15 for all visits). ClinSev related to GenSev (r = 0.41, p < 0.001; r = 0.42 for all visits). NFTI-QOL showed good reliability and ability to detect significant longitudinal changes in the QOL of individuals. The moderate relationships of NFTI-QOL with a clinician- and genetic-rated severity suggest that NFTI-QOL taps into NF2 patient experiences that are not encompassed by ClinSev rating or genotype 3)

1)

Hornigold, R. E., Golding, J. F., Leschziner, G., Obholzer, R., Gleeson, M. J., Thomas, N., Walsh, D., Saeed, S., & Ferner, R. E. (2012). The NFTI-QOL: A Disease-Specific Quality of Life Questionnaire for Neurofibromatosis 2. Journal of Neurological Surgery. Part B, Skull Base, 73(2), 104-111. https://doi.org/10.1055/s-0032-1301396
2)

Lawson McLean AC, Freier A, Lawson McLean A, Kruse J, Rosahl S. The German version of the neurofibromatosis 2 impacts on quality of life questionnaire correlates with severity of depression and physician-reported disease severity. Orphanet J Rare Dis. 2023 Jan 6;18(1):3. doi: 10.1186/s13023-022-02607-z. PMID: 36604703.
3)

Ferner RE, Shaw A, Evans DG, McAleer D, Halliday D, Parry A, Raymond FL, Durie-Gair J, Hanemann CO, Hornigold R, Axon P, Golding JF. Longitudinal evaluation of quality of life in 288 patients with neurofibromatosis 2. J Neurol. 2014 May;261(5):963-9. doi: 10.1007/s00415-014-7303-1. Epub 2014 Mar 12. PMID: 24619350; PMCID: PMC4008785.

Cervical Sympathetic Nerve Block for cerebral vasospasm

Cervical Sympathetic Nerve Block for cerebral vasospasm

Sympathetic perivascular nerve fibers originate from the superior cervical ganglion (SCG) to innervate the cerebral vasculature, with activation resulting in vasoconstriction. Sympathetic pathways are thought to be a significant contributor to cerebral vasospasm 1).

A simple treatment such as a cervical sympathetic nerve block may be an effective therapy but is not routinely performed as cerebral vasospasm treatment/DCI. cervical sympathetic nerve block consists of injecting local anesthetic at the level of the cervical sympathetic trunk, which temporarily blocks the innervation of the cerebral arteries to cause arterial vasodilatation. cervical sympathetic nerve block is a local, minimally invasive, low cost and safe technique that can be performed at the bedside and may offer significant advantages as a complementary treatment in combination with more conventional neurointerventional surgery interventions. Bombardieri et al. reviewed the literature that describes cervical sympathetic nerve block for vasospasm/DCI prevention or treatment in humans after aSAH. The studies outlined in this review show promising results for a cervical sympathetic nerve block as a treatment for vasospasm/DCI. Further research is required to standardize the technique, explore how to integrate a cervical sympathetic nerve block with conventional neurointerventional surgery treatments of vasospasm and DCI, and study its long-term effect on neurological outcomes 2).

SCG was surgically identified in 15 swine and were electrically stimulated to achieve sympathetic activation. CT perfusion scans were performed to assess for changes in cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time-to-maximum (TMax). Syngo. via software was used to determine regions of interest and quantify perfusion measures.

Results: SCG stimulation resulted in 20-30% reduction in mean ipsilateral CBF compared to its contralateral unaffected side (p < 0.001). Similar results of hypoperfusion were seen with CBV, MTT and TMax with SCG stimulation. Prior injection of lidocaine to SCG inhibited the effects of SCG stimulation and restored perfusion comparable to baseline (p > 0.05).

Conclusion: In swine, SCG stimulation resulted in significant cerebral perfusion deficit, and this was inhibited by prior local anesthetic injection into the SCG. Inhibiting sympathetic activation by targeting the SCG may be an effective treatment for sympathetic-mediated cerebral hypoperfusion 3).

Hu et al. investigated the therapeutic effects of SGB in a rat model of subarachnoid hemorrhage (SAH) complicated by delayed CVS and explore the underlying mechanisms. The SAH model was established by the double injection of autologous arterial blood into the cisterna magna. They simulated SGB by transection of the cervical sympathetic trunk (TCST), and measured changes in the diameter, perimeter, and cross-sectional area of the basilar artery (BA) and middle cerebral artery (MCA) to evaluate its vasodilatory effect. To investigate the underlying mechanisms, we determined the expression level of vasoactive molecules endothelin-1 (ET-1) and calcitonin gene-related peptide (CGRP) in the plasma, and apoptotic modulators Bcl-2 and Bax in the hippocampus. We found a significant increase in the diameter, perimeter, and cross-sectional area of the BA and right MCA in SAH rats subjected to TCST. Application of SGB significantly reduced the expression of ET-1 while increasing that of CGRP in SAH rats. We also found a significant increase in the expression of Bcl-2 and a decrease in the expression of Bax in the hippocampus of SAH rats subjected to TCST, when compared to untreated SAH rats. The mechanism of action of SGB is likely mediated through alterations in the ratio of ET-1 and CGRP, and Bax and Bcl-2. These results suggest that SGB can alleviate the severity of delayed CVS by inducing dilation of intracerebral blood vessels, and promoting anti-apoptotic signaling. Our findings provide evidence supporting the use of SGB as an effective and well-tolerated approach to the treatment of CVS in various clinical settings 4)

After successful modeling of cervical sympathetic block, 18 healthy male white rabbits were randomly divided into three groups (n=6), ie, sham operation group (Group A), SAH group (Group B) and SAH with cervical sympathetic block group (Group C). Models of delayed CVS were established by puncturing cisterna magna twice with an injection of autologous arterial blood in Groups B and C. A sham injection of blood through cisterna magna was made in Group A. 0.5 ml saline was injected each time through a catheter for cervical sympathetic block after the first injection of blood three times a day for 3 d in Group B (bilateral alternating). 0.5 ml of 0.25% bupivacaine was injected each time through a catheter for cervical sympathetic block after the first injection of blood three times a day for 7 d in Group B. 2 ml venous blood and cerebrospinal fluid were obtained before (T1), 30 min (T2) and 7 d (T3) after the first injection of blood, respectively, and conserved in a low temperature refrigerator. Basilar artery value at T1, T2 and T3 was measured via cerebral angiography. The degree of damage to nervous system at T1 and T3 was recorded.

Results: There was no significant difference in diameter of basilar artery at T1 among three groups. The diameters of basilar artery at T2 and T3 of Groups B and C were all smaller than that in Group A, which was smaller than Group C, with a significant difference. There was no significant difference in NO and NOS in plasma and cerebrospinal fluid among three groups. The NO and NOS contents at T2 and T3 of Groups B and C were all lower than Group A; Group C was higher than Group B, with a significant difference. The nerve function at T3 of Groups B and C were all lower than Group A and that of Group C higher than Group B, with a significant difference.

Cervical sympathetic block can relieve cerebral vasospasm after subarachnoid hemorrhage and increase NO content and NOS activity in plasma and cerebrospinal fluid to promote neural functional recovery 5)

1) , 3)

Kim WJ, Dacey M, Samarage HM, Zarrin D, Goel K, Chan C, Qi X, Wang AC, Shivkumar K, Ardell J, Colby GP. Sympathetic nervous system hyperactivity results in potent cerebral hypoperfusion in swine. Auton Neurosci. 2022 Sep;241:102987. doi: 10.1016/j.autneu.2022.102987. Epub 2022 May 6. PMID: 35567916; PMCID: PMC9659432.
2)

Bombardieri AM, Albers GW, Rodriguez S, Pileggi M, Steinberg GK, Heit JJ. Percutaneous cervical sympathetic block to treat cerebral vasospasm and delayed cerebral ischemia: a review of the evidence. J Neurointerv Surg. 2022 Dec 6:jnis-2022-019838. doi: 10.1136/jnis-2022-019838. Epub ahead of print. PMID: 36597947.
4)

Hu N, Wu Y, Chen BZ, Han JF, Zhou MT. Protective effect of stellate ganglion block on delayed cerebral vasospasm in an experimental rat model of subarachnoid hemorrhage. Brain Res. 2014 Oct 17;1585:63-71. doi: 10.1016/j.brainres.2014.08.012. Epub 2014 Aug 13. PMID: 25128600.
5)

Chun-jing H, Shan O, Guo-dong L, Hao-xiong N, Yi-ran L, Ya-ping F. Effect of cervical sympathetic block on cerebral vasospasm after subarachnoid hemorrhage in rabbits. Acta Cir Bras. 2013 Feb;28(2):89-93. doi: 10.1590/s0102-86502013000200001. PMID: 23370920.

Axonova Medical

Axonova Medical

https://axonovamed.com/

Functional restoration following major peripheral nerve injury (PNI) is challenging, given slow axon growth rates and eventual regenerative pathway degradation in the absence of axons. Smith et al. from the Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, Axonova Medical are developing tissue-engineered nerve grafts (TENGs) to simultaneously “bridge” missing nerve segments and “babysit” regenerative capacity by providing living axons to guide host axons and maintain the distal pathway. TENGs were biofabricated using porcine neurons and “stretch-grown” axon tracts. TENG neurons survived and elicited axon-facilitated axon regeneration to accelerate regrowth across both short (1 cm) and long (5 cm) segmental nerve defects in pigs. TENG axons also closely interacted with host Schwann cells to maintain pro-regenerative capacity. TENGs drove regeneration across 5-cm defects in both motor and mixed motor-sensory nerves, resulting in dense axon regeneration and electrophysiological recovery at levels similar to autograft repairs. This approach of accelerating axon regeneration while maintaining the pathway for long-distance regeneration may achieve recovery after currently unrepairable PNIs 1).

Burrell JC, Das S, Laimo FA, Katiyar KS, Browne KD, Shultz RB, Tien VJ, Vu PT, Petrov D, Ali ZS, Rosen JM, Cullen DK. Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats. Bioact Mater. 2022 Mar 24;18:339-353. doi: 10.1016/j.bioactmat.2022.03.018. PMID: 35415305; PMCID: PMC8965778.

Wofford KL, Shultz RB, Burrell JC, Cullen DK. Neuroimmune interactions and immunoengineering strategies in peripheral nerve repair. Prog Neurobiol. 2022 Jan;208:102172. doi: 10.1016/j.pneurobio.2021.102172. Epub 2021 Sep 4. PMID: 34492307; PMCID: PMC8712351.

Shultz RB, Katiyar KS, Laimo FA, Burrell JC, Browne KD, Ali ZS, Cullen DK. Biopreservation of living tissue engineered nerve grafts. J Tissue Eng. 2021 Aug 11;12:20417314211032488. doi: 10.1177/20417314211032488. PMID: 34394908; PMCID: PMC8361542.

O’Donnell JC, Purvis EM, Helm KVT, Adewole DO, Zhang Q, Le AD, Cullen DK. An implantable human stem cell-derived tissue-engineered rostral migratory stream for directed neuronal replacement. Commun Biol. 2021 Jul 15;4(1):879. doi: 10.1038/s42003-021-02392-8. PMID: 34267315; PMCID: PMC8282659.

Katiyar KS, Burrell JC, Laimo FA, Browne KD, Bianchi JR, Walters A, Ayares DL, Smith DH, Ali ZS, Ledebur HC, Cullen DK. Biomanufacturing of Axon-Based Tissue Engineered Nerve Grafts Using Porcine GalSafe Neurons. Tissue Eng Part A. 2021 Oct;27(19-20):1305-1320. doi: 10.1089/ten.TEA.2020.0303. Epub 2021 Apr 9. PMID: 33514288; PMCID: PMC8610031.

1)

Smith DH, Burrell JC, Browne KD, Katiyar KS, Ezra MI, Dutton JL, Morand JP, Struzyna LA, Laimo FA, Chen HI, Wolf JA, Kaplan HM, Rosen JM, Ledebur HC, Zager EL, Ali ZS, Cullen DK. Tissue-engineered grafts exploit axon-facilitated axon regeneration and pathway protection to enable recovery after 5-cm nerve defects in pigs. Sci Adv. 2022 Nov 4;8(44):eabm3291. doi: 10.1126/sciadv.abm3291. Epub 2022 Nov 4. PMID: 36332027.

Peripheral nerve surgery training

Peripheral nerve surgery training

Neurosurgery residents exceeded the required minimum number of Peripheral nerve surgery and were increasingly more exposed to PNS. However, compared with their counterparts in orthopedic and plastic surgery, neurosurgery residents performed significantly fewer cases. Exposure for neurosurgery residents remains unchanged over the study period while plastic surgery residents experienced an increase in case volume. The deficiency in exposure for neurosurgical residents must be addressed to harness interest and proficiency in PNS 1).

In 2003, the goal of a study was to determine current practice patterns and attitudes of neurosurgeons toward peripheral nerve surgery.

A 13-question survey was mailed to all active members of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. Collected responses were entered into a database and were analyzed using statistical software.

Of 3800 surveys mailed there were 1728 responses for a 45% response rate. Analysis of the data revealed that respondents had a greater comfort level with simple peripheral nerve procedures, such as carpal tunnel release, and a lack of comfort with more complex peripheral nerve procedures, such as brachial plexus exploration. The majority of simple cases were treated by the surveyed neurosurgeons, whereas the majority of complex cases were referred to other surgeons, primarily to other neurosurgeons. The type of medical practice (academic, group, or solo) and the location of the practice (major city, small city, suburban setting, or rural area) showed a statistically significant correlation to simple case referral patterns, whereas the length of time since the respondent underwent training did not. Practice type and location, and years since training showed a statistically significant correlation to complex case referral patterns. Only 48.7% of the respondents believed that they had been given sufficient exposure to peripheral nerve surgery during residency training. The overwhelming majority (97.2%) of respondents favored keeping peripheral nerve surgery as part of the neurosurgical curriculum 2).

Peripheral nerve surgical competency

Peripheral nerve surgical competency.

Fellowships

Peripheral Nerve Surgery Fellowship (Mayo Clinic Rochester).

Salt Lake City

University of Calgary.

Courses

Copenhagen Peripheral Nerve Surgery Course 2022 https://peripheral-nerve-surgery.com/

1)

Gohel P, White M, Agarwal N, Fields P D, Ozpinar A, Alan N. Longitudinal Analysis of Peripheral Nerve Surgery Training: Comparison of Neurosurgery to Plastic and Orthopedic Surgery. World Neurosurg. 2022 Jan 30:S1878-8750(22)00108-5. doi: 10.1016/j.wneu.2022.01.094. Epub ahead of print. PMID: 35108647.
2)

Maniker A, Passannante M. Peripheral nerve surgery and neurosurgeons: results of a national survey of practice patterns and attitudes. J Neurosurg. 2003 Jun;98(6):1159-64. doi: 10.3171/jns.2003.98.6.1159. PMID: 12816257.

Transthyretin amyloidosis

Transthyretin amyloidosis

Hereditary transthyretin amyloidosis (ATTR) is usually characterised by a progressive peripheral and autonomic neuropathy often with associated cardiac failure and is due to dominantly inherited transthyretin mutations causing accelerated amyloid deposition. The UK population is unique in that the majority of patients have the T60A missense mutation in ATTR where tyrosine is replaced by adenine at position 60. This has been traced to a single founder mutation from north-west Ireland 1).

An accurate and timely diagnosis of amyloid neuropathy can greatly impact on the outcomes for patients, especially as there will soon be new gene-silencing treatments for hereditary transthyretin amyloidosis 2).

Results raise the possibility of a diagnostic role for MIBG scintigraphy at an early stage of cardiac involvement in TTR-mutated carriers, in addition to its well-established prognostic value 3).

Case series

Godara et al. investigated consecutive patients undergoing surgery for spinal stenosis (SS) for ATTR deposition in the resected ligamentum flavum (LF) and concomitant risk of cardiac amyloidosis. Each surgical specimen (LF) was stained with Congo red, and if positive, the amyloid deposits were typed by mass spectrometry. Patients with positive specimens underwent standard of care evaluation with fat pad aspirates, serum and urine protein electrophoresis with immunofixation, free light-chain assay, TTR gene sequencing and technetium 99 m-pyrophosphate-scintigraphy. In 2018-2019, 324 patients underwent surgery for SS and 43 patients (13%) had ATTR in the LF with wild-type TTR gene sequences. Two cases of ATTRwt cardiac amyloidosis were diagnosed and received treatment. In this large series, ATTRwt was identified in 13% of the patients undergoing laminectomy for SS. Patients with amyloid in the ligamentum flavum were older and had a higher prevalence of CTS, suggesting a systemic form of ATTR amyloidosis involving connective tissue. Further prospective study of patients with SS at risk for systemic amyloidosis is warranted 4).

Carr et al. presented the findings from an observational cohort study of patients with ATTR attending the National Hospital Inherited Neuropathy Clinic between 2009 and 2013. Detailed clinical neurological and electrophysiological data were collected on all patients alongside correlating autonomic and cardiac assessments. Follow-up data were available on a subset.

Forty-four patients with genetically confirmed ATTR were assessed; 37 were symptomatic; mean age at onset=62 years, range=38-75 years; 75.7% male. T60A was the most common mutation (17/37), followed by V30M (5/37). A severe, rapidly progressive, predominantly length dependent axonal sensorimotor neuropathy was the predominant phenotype. T60A patients were distinguished by earlier and more frequent association with carpal tunnel syndrome; a predominance of negative sensory symptoms at onset; significant vibration deficits; and a non-length dependent progression of motor deficit. Progression of the neuropathy was observed over a relatively short follow-up period (2 years) in 20 patients with evidence of clinically measurable annual change in Medical Research Council (MRC) sum score (-1.5 points per year) and Charcot Marie Tooth Neuropathy Score (CMTNS:2.7 points per year), and a congruent trend in the electrophysiological measures used.

The description of the ATTR neuropathy phenotype, especially in the T60A patients, should aid early diagnosis as well as contribute to the understanding of its natural history 5).

Case reports

Carret al., described a patient with genetically confirmed Transthyretin amyloidosis (ATTR), a family history of the disease and histological confirmation following carpal tunnel release surgery but no other manifestations. The first major neurological or systemic manifestation was cauda equina syndrome with ATTR deposits contributing to lumbar spinal stenosis. Recent gene therapy trials showed improvement in the neuropathy in TTR amyloidosis. This case highlights the need for awareness of the heterogeneous neurological phenotype seen in ATTR to aid earlier diagnosis especially now that disease modifying therapies are available 6).

Patel et al., reported a case of transthyretin amyloidosis with myopathy, neuropathy, and cardiomyopathy resulting from an exceedingly rare mutation transthyretin Ala120Ser (c.418G > T, p.Ala140Ser) 7).

Oculoleptomeningeal amyloidosis (OLMA) represents a rare subtype of familial transthyretin (TTR) amyloidosis, characterized by deposition of amyloid in cranial and spinal leptomeninges along with ocular involvement. Of >100 TTR mutations identified, few have been associated with OLMA. Herein we describe the first report of leptomeningeal amyloidosis associated with the c.381T>G (p.Ile127Met) TTR mutation, linking this variant to the OLMA phenotype. CASE DESCRIPTION:

A 53 year-old man presented with a 2-year history of progressive symptoms including upper and lower limb weakness, ataxia, and peripheral and autonomic neuropathy. Neuroimaging, including gadolinium-enhanced magnetic resonance imaging of the brain and spinal axis, identified diffuse leptomeningeal enhancement along the brainstem and spinal cord plus evidence of hemosiderosis. Pathologic and genetic analyses of biopsy material from enhancing intradural extramedullary tissue at the thoracolumbar junction was diagnostic of amyloidosis of a transthyretin type secondary to a TTR c.381T>G (p.Ile127Met) mutation.

OLMA represents a rare subtype of heritable transthyretin amyloidosis that may present with progressive neurological decline secondary to central nervous system leptomeningeal amyloid deposition. This case identifies the c.381T>G (p.Ile127Met) TTR mutation variant as being implicated in the OLMA phenotype 8).

Cervicomedullary compression as the main manifestation of wild-type transthyretin amyloidosis 9).

present an unusual case of V122I amyloidosis with features of amyloid neuropathy and myopathy, supported by histological confirmation in both sites and diffuse tracer uptake on (99m)Tc-3,3-Diphosphono-1,2-Propanodicarboxylic acid (DPD) scintigraphy throughout skeletal and cardiac muscle. A 64 year old Jamaican man presented with cardiac failure. Cardiac MR revealed infiltrative cardiomyopathy; abdominal fat aspirate confirmed the presence of amyloid, and he was homozygous for the V122I variant of transthyretin. He also described general weakness and EMG demonstrated myopathic features. Sural nerve and vastus lateralis biopsy showed TTR amyloid. The patient is being treated with diflunisal, an oral TTR stabilising agent. Symptomatic myopathy and neuropathy with confirmation of tissue amyloid deposition has not previously been described. Extracardiac amyloidosis has implications for diagnosis and treatment 10)

1) , 5)

Carr AS, Pelayo-Negro AL, Evans MR, Laurà M, Blake J, Stancanelli C, Iodice V, Wechalekar AD, Whelan CJ, Gillmore JD, Hawkins PN, Reilly MM. A study of the neuropathy associated with transthyretin amyloidosis (ATTR) in the UK. J Neurol Neurosurg Psychiatry. 2016 Jun;87(6):620-7. doi: 10.1136/jnnp-2015-310907. Epub 2015 Aug 4. PubMed PMID: 26243339.
2)

Kapoor M, Rossor AM, Jaunmuktane Z, Lunn MPT, Reilly MM. Diagnosis of amyloid neuropathy. Pract Neurol. 2018 Dec 30. pii: practneurol-2018-002098. doi: 10.1136/practneurol-2018-002098. [Epub ahead of print] PubMed PMID: 30598431.
3)

Piekarski E, Chequer R, Algalarrondo V, Eliahou L, Mahida B, Vigne J, Adams D, Slama MS, Le Guludec D, Rouzet F. Cardiac denervation evidenced by MIBG occurs earlier than amyloid deposits detection by diphosphonate scintigraphy in TTR mutation carriers. Eur J Nucl Med Mol Imaging. 2018 Jul;45(7):1108-1118. doi: 10.1007/s00259-018-3963-x. Epub 2018 Mar 6. PubMed PMID: 29511839.
4)

Godara A, Riesenburger RI, Zhang DX, Varga C, Fogaren T, Siddiqui NS, Yu A, Wang A, Mastroianni M, Dowd R, Nail TJ, McPhail ED, Kurtin PJ, Theis JD, Toskic D, Arkun K, Pilichowska M, Kryzanski J, Patel AR, Comenzo R. Association between spinal stenosis and wild-type ATTR amyloidosis. Amyloid. 2021 Jul 15:1-8. doi: 10.1080/13506129.2021.1950681. Epub ahead of print. PMID: 34263670.
6)

Carr AS, Shah S, Choi D, Blake J, Phadke R, Gilbertson J, Whelan CJ, Wechalekar AD, Gillmore JD, Hawkins PN, Reilly MM. Spinal Stenosis in Familial Transthyretin Amyloidosis. J Neuromuscul Dis. 2019 Mar 7. doi: 10.3233/JND-180348. [Epub ahead of print] PubMed PMID: 30856118.
7)

Patel K, Tagoe C, Bieri P, Weidenheim K, Tauras JM. A case of transthyretin amyloidosis with myopathy, neuropathy, and cardiomyopathy resulting from an exceedingly rare mutation transthyretin Ala120Ser (c.418G > T, p.Ala140Ser). Amyloid. 2018 Sep;25(3):211-212. doi: 10.1080/13506129.2018.1491398. Epub 2018 Jul 24. PubMed PMID: 30039724.
8)

Mathieu F, Morgan E, So J, Munoz DG, Mason W, Kongkham P. Oculoleptomeningeal Amyloidosis Secondary to the Rare Transthyretin c.381T>G (p.Ile127Met) Mutation. World Neurosurg. 2018 Mar;111:190-193. doi: 10.1016/j.wneu.2017.12.096. Epub 2017 Dec 23. PubMed PMID: 29277593.
9)

Rezania K, Pytel P, Highsmith WE, Gabikian P. Cervicomedullary compression as the main manifestation of wild-type transthyretin amyloidosis. Amyloid. 2017 Jun;24(2):133-134. doi: 10.1080/13506129.2017.1331907. Epub 2017 May 23. PubMed PMID: 28532173.
10)

Carr AS, Pelayo-Negro AL, Jaunmuktane Z, Scalco RS, Hutt D, Evans MR, Heally E, Brandner S, Holton J, Blake J, Whelan CJ, Wechalekar AD, Gillmore JD, Hawkins PN, Reilly MM. Transthyretin V122I amyloidosis with clinical and histological evidence of amyloid neuropathy and myopathy. Neuromuscul Disord. 2015 Jun;25(6):511-5. doi: 10.1016/j.nmd.2015.02.001. Epub 2015 Feb 14. PubMed PMID: 25819286.

Electrical stimulation for peripheral nerve injury treatment

Electrical stimulation for peripheral nerve injury treatment

Peripheral nerve injury afflicts individuals from all walks of life. Despite the peripheral nervous system’s intrinsic ability to regenerate, many patients experience incomplete functional recovery. Surgical repair aims to expedite this recovery process in the most thorough manner possible. However, full recovery is still rarely seen especially when nerve injury is compounded with polytrauma where surgical repair is delayed. Pharmaceutical strategies supplementary to nerve microsurgery have been investigated but surgery remains the only viable option 1).

Electrical stimulation is regarded pivotal to promote repair of nerve injury, however, failed to get extensive application in vivo due to the challenges in noninvasive electrical loading accompanying with construction of biomimetic cell niche.

Building on decades of experimental evidence in animal models, several recent, prospective, randomized clinical trials have affirmed electrical stimulation as a clinically translatable technique to enhance functional recovery in patients with peripheral nerve injuries requiring surgical treatment 2).

Implantable wireless stimulators can deliver therapeutic electrical stimulation to injured peripheral nerve tissue. Implantable wireless nerve stimulators might represent a novel means of facilitating therapeutic electrical stimulation in both intraoperative and postoperative settings 3).

Zhang et al. demonstrated a new concept of magneto responsive electric 3D matrix for remote and wireless electrical stimulation. By the preparation of magnetoelectric core/shell structured Fe3 O4 @BaTiO3 NPs-loaded hyaluronan/collagen hydrogels, which recapitulate considerable magneto-electricity and vital features of native neural extracellular matrix, the enhancement of neurogenesis both in cellular level and spinal cord injury in vivo with external pulsed magnetic field applied is proved. The findings pave the way for a novel class of remote controlling and delivering electricity through extracellular niches-mimicked hydrogel network, arising prospects not only in neurogenesis but also in human-computer interaction with higher resolution 4).

The frequency of stimulation is an important factor in the success of both quality and quantity of axon regeneration as well as growth of the surrounding myelin and blood vessels that support the axon. Histological analysis and measurement of regeneration showed that low frequency stimulation had a more successful outcome than high frequency stimulation on regeneration of damaged sciatic nerves.

The use of autologous nerve grafting procedures that involve redirection of regenerative donor nerve fibers into the graft conduit has been successful in restoring target muscle function. Localized delivery of soluble neurotrophic factors may help promote the rate of axon regeneration observed within these graft conduits.

An expanding area of nerve regeneration research deals with the development of scaffolding and bio-conduits. Scaffolding developed from biomaterial would be useful in nerve regeneration if they successfully exhibit essentially the same role as the endoneurial tubes and Schwann cell do in guiding regrowing axons.

The surgeon, who treats nerve injuries, should have knowledge about how peripheral nerves react to trauma, particularly an understanding about the extensive pathophysiological alterations that occur both in the peripheral and in the central nervous system. A large number of factors influence the functional outcome, where the surgeon only can affect a few of them. In view of the new knowledge about the delicate intracellular signaling pathways that are rapidly initiated in neurons and in nonneuronal cells with the purpose to induce nerve regeneration, the timing of nerve repair and reconstruction after injury has gained more interest. It is crucial to understand and to utilize the inborn mechanisms for survival and regeneration of neurons and for activation, survival, and proliferation of the Schwann cells and other cells that are acting after a nerve injury. Thus, experimental and clinical data clearly point toward the advantage of early nerve repair and reconstruction of injuries. Following an appropriate diagnosis of a nerve injury, the nerve should be promptly repaired or reconstructed, and new rehabilitation strategies should early be initiated. Considering nerve transfers in the treatment arsenal can shorten the time of nerve reinnervation of muscle targets. Timing of nerve repair and reconstruction is crucial after nerve injury 5).

1)

Willand MP, Nguyen MA, Borschel GH, Gordon T. Electrical Stimulation to Promote Peripheral Nerve Regeneration. Neurorehabil Neural Repair. 2016 Jun;30(5):490-6. doi: 10.1177/1545968315604399. Epub 2015 Sep 10. PMID: 26359343.
2)

Zuo KJ, Gordon T, Chan KM, Borschel GH. Electrical stimulation to enhance peripheral nerve regeneration: Update in molecular investigations and clinical translation. Exp Neurol. 2020 Oct;332:113397. doi: 10.1016/j.expneurol.2020.113397. Epub 2020 Jul 3. PMID: 32628968.
3)

MacEwan MR, Gamble P, Stephen M, Ray WZ. Therapeutic electrical stimulation of injured peripheral nerve tissue using implantable thin-film wireless nerve stimulators. J Neurosurg. 2018 Feb 9:1-10. doi: 10.3171/2017.8.JNS163020. Epub ahead of print. PMID: 29424647.
4)

Zhang Y, Chen S, Xiao Z, Liu X, Wu C, Wu K, Liu A, Wei D, Sun J, Zhou L, Fan H. Magnetoelectric Nanoparticles Incorporated Biomimetic Matrix for Wireless Electrical Stimulation and Nerve Regeneration. Adv Healthc Mater. 2021 Jun 27:e2100695. doi: 10.1002/adhm.202100695. Epub ahead of print. PMID: 34176235.
5)

Dahlin LB. The role of timing in nerve reconstruction. Int Rev Neurobiol. 2013;109:151-64. doi: 10.1016/B978-0-12-420045-6.00007-9. Review. PubMed PMID: 24093611.

Iatrogenic peripheral nerve injury

Iatrogenic peripheral nerve injury

Treatment

Iatrogenic peripheral nerve injury is a considerable social and economic concern and the majority of cases are preventable. Complications should be referred to and dealt with promptly by experienced surgeons, to ensure the best chances for optimal functional recovery. Their prevention should be emphasized. Their management should include ensuring early diagnosis, administering an appropriate treatment with rehabilitation, rendering psychological support, and providing control of pain 1).

The combination of morphological assessment (neurosonography) with functional assessment (nerve conduction studies) is of paramount importance in the management of traumatic peripheral nerve injuries. If on sonography, the nerve appears intact, then intraoperative nerve conduction studies the functionality of the nerve. If conduction is impaired (signifying the presence of a neuroma-in-continuity), then nerve grafting is done. If the conduction is somewhat preserved, neurolysis is performed 2).

If it is noted during an operation that a nerve has been severed, it should be repaired immediately during the same operation (primary repair) or within 2–3 weeks (early secondary repair) 3).

The same is true when the nerve is torn or damaged but not cleanly cut. The same operative approach is used as for any other nerve injury. The repair ideally is done with microsurgical tools and magnifying devices, insuring maximal visualization for the repair.

Once again, this ideal situation with the immediate repair is seldom achieved. Usually, the cause of the damage is unknown. In our experience, the operative report rarely provides useful information. When the mechanism for the damage is unknown but there is reason to think that the nerve may regenerate itself, we prefer to wait 3 months with monthly neurological examinations. If at this time, the deficit has not changed or only minimally improved, the nerve should be surgically explored in the next month. If the neurosonographic examination after exposure of the nerve identifies a neuroma, one should not delay. The operation should ideally occur within 3 weeks 4).

A severed nerve should be reconstructed, if possible. Usually, this requires nerve grafting. The sural nerve on the lateral calf is usually used as a source. Other cutaneous nerves such as the saphenous nerve and the medial antebrachial cutaneous nerve can also be used 5). If the nerve appears to be intact, then intraoperative nerve conduction studies help assess how functional it is in the area of damage. If conductivity is impaired, then the affected segment of the nerve surrounded by scar tissue—usually thickened and diagnosed as a neuroma in continuity—is excised and replaced by a transplant. In other cases, when conductivity studies are more promising, it suffices to free the nerve up from the surrounding reactive tissues (neurolysis). In recent years intraoperative neuro sonography has been employed, facilitating the evaluation of individual nerve fascicles, helping distinguish between a complete neuroma in continuity without any residual fascicles and a partial lesion still containing functioning fascicles 6).

The combination of the functional evaluation (nerve conduction studies) and the morphologic assessment (neuro sonography) is very helpful in the surgical management of traumatic injuries in peripheral nerve surgery. The exact approach is documented in the interdisciplinary guidelines of the AWMF “Versorgung peripherer Nervenverletzungen” 7).

A key factor in improving the prognosis is physical therapy, both after the deficit is identified and then post-operatively until re-innervation of the affected muscles has occurred. Electric stimulation therapy is also worthwhile in our option. In this way, the muscle structures can be better maintained until nerve regeneration has occurred.

Case series

Dubuisson et al. analyzed the management of iatrogenic peripheral nerve injury (iNI) in 42 patients.

The iNI occurred mostly during a surgical procedure (n = 39), either on a nerve or plexus (n = 13), on bone, joint, vessel, or soft tissue (n = 24) or because of malpositioning (n = 2). The most commonly injured nerves were the brachial plexus, radial nerve, sciatic nerve, femoral nerve, or peroneal nerves. 42.9% of the patients were referred to later than 6 months. A neurological deficit was present in 37 patients and neuropathic pain in 17. Two patients were lost to follow-up. Conservative treatment was applied in 23 patients because of good spontaneous recovery or compensation or because of expected bad prognosis whatever the treatment. Surgical treatment was performed in 17 patients because of known nerve section (n = 2), persistent neurological deficit (n = 12) or invalidating neuropathic pain (n = 3); nerve reconstruction with grafts (n = 8) and neurolysis (n = 8) were the most common procedures. The outcome was satisfactory in 50%. Potential reasons for poor outcomes were a very proximal injury, placement of very long grafts, delayed referral, and predominance of neuropathic pain. According to the literature, delayed referral of iNI for treatment is frequent. They provides an illustrative case of a young girl operated on at 6.5 months for femoral nerve reconstruction with grafts while the nerve section was obvious from the operative note and pathological tissue analysis. Litigation claims (n = 10) resulted in malpractice (n = 2) or therapeutic area (n = 5) (3 unavailable conclusions).

NI can result in considerable disability, pain, and litigation. Optimal management is required 8).

Rasulić et al. describe and analyze iatrogenic nerve injuries in a total of 122 consecutive patients who received surgical treatment at there institution during a period of 10 years, from January 1, 2003, to December 31, 2013. The final outcome evaluation was performed 2 years after surgical treatment.

The most common causes of iatrogenic nerve injuries among patients in the study were the operations of bone fractures (23.9%), lymph node biopsy (19.7%), and carpal tunnel release (18%). The most affected nerves were median nerve (21.3%), accessory nerve (18%), radial nerve (15.6%), and peroneal nerve (11.5%). In 74 (60.7%) patients, surgery was performed 6 months after the injury, and in 48 (39.3%) surgery was performed within 6 months after the injury. In 80 (65.6%) patients, we found lesion in discontinuity, and in 42 (34.4%) patients lesion in continuity. The distribution of surgical procedures performed was as follows: autotransplantation (51.6%), neurolysis (23.8%), nerve transfer (13.9%), direct suture (8.2%), and resection of neuroma (2.5%). In total, we achieved satisfactory recovery in 91 (74.6%), whereas the result was dissatisfactory in 31 (25.4%) patients.

Patients with iatrogenic nerve injuries should be examined as soon as possible by experts with experience in traumatic nerve injuries so that the correct diagnosis can be reached and the appropriate therapy planned. The timing of reconstructive surgery and the technique used are the crucial factors for functional recover 9).

340 patients underwent surgery for iatrogenic nerve injuries over a 23-year period in the District Hospital of Günzburg (Neurosurgical Department of the University of Ulm). In a study published by the authors in 2001, 17.4% of the traumatic nerve lesions treated were iatrogenic. 94% of iatrogenic nerve injuries occurred during surgical procedures 10).

References

1)

Kumar A, Shukla D, Bhat DI, Devi BI. Iatrogenic peripheral nerve injuries. Neurol India. 2019;67(Supplement):S135-S139. doi:10.4103/0028-3886.250700
2)

Sinha S. Management protocol in the case of iatrogenic peripheral nerve injuries. Neurol India. 2019;67(Supplement):S140-S141. doi:10.4103/0028-3886.250696
3) , 4) , 5) , 7)

Deutsche Gesellschaft für Handchirurgie (DGH), Deutsche Gesellschaft für Neurologie (DGN), Deutsche Gesellschaft für Neurochirurgie (DGNC), Deutsche Gesellschaft für Orthopädie und Orthopädische Chirurgie (DGOOC), Deutsche Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC), Deutsche Gesellschaft für Unfallchirurgie (DGU) Leitlinen: Versorgung peripherer Nervenverletzungen. http://www.awmf.org/leitlinien/detail/ll/005-010.html Stand 30.06.2013
6)

Koenig RW, Schmidt TE, Heinen CPG, et al. Intraoperative high-resolution ultrasound: a new technique in the management of peripheral nerve disorders. Clinical article Journal of Neurosurgery. 2011;114:514–521
8)

Dubuisson A, Kaschten B, Steinmetz M, et al. Iatrogenic nerve injuries: a potentially serious medical and medicolegal problem. About a series of 42 patients and review of the literature [published online ahead of print, 2020 Jul 11]. Acta Neurol Belg. 2020;10.1007/s13760-020-01424-0. doi:10.1007/s13760-020-01424-0
9)

Rasulić L, Savić A, Vitošević F, et al. Iatrogenic Peripheral Nerve Injuries-Surgical Treatment and Outcome: 10 Years’ Experience. World Neurosurg. 2017;103:841-851.e6. doi:10.1016/j.wneu.2017.04.099
10)

Antoniadis G, Kretschmer T, Pedro MT, König RW, Heinen CP, Richter HP. Iatrogenic nerve injuries: prevalence, diagnosis and treatment. Dtsch Arztebl Int. 2014;111(16):273-279. doi:10.3238/arztebl.2014.0273

Vagal Nerve Schwannoma

Vagal Nerve Schwannoma

Epidemiology

Schwannoma arising from the vagus nerve is an uncommon (2–5%) benign nerve tumour.

Vagal Nerve Schwannomas are usually confined to the retrostyloid parapharyngeal space, although patients with schwannomas that extend into the posterior cranial fossa through the jugular foramen have been reported

Schwannomas arising from the vagus nerve are extremely rare in children, with only 16 cases reported in the world literature 1).

Clinical features

They usually presents as an asymptomatic slow growing mass 2).

Most cases of schwannomas manifest between the third and sixth decades of the patient’s life as a slow growing firm, painless mass in the lateral neck. Hoarseness, pain, or cough may be the presenting complaints. They displace the carotid arteries anteriorly and medially, jugular vein laterally and posteriorly. These swellings are mobile transversely but not vertically 3).

Diagnosis

Diagnosis is based on clinical suspicion and confirmation obtained by means of surgical pathology.

Differential diagnosis

Schwannomas of the vagus nerve must be differentiated from the carotid body and glomus vagale tumors because the distinction may influence treatment planning.

Treatment

Surgical excision is the treatment of choice for vagal schwannoma, with recurrence being rare.

Intermittent intraoperative neuromonitoring via selective stimulation of splayed motor fibers running on the schwannoma surface to elicit a compound muscle action potential has been previously reported as a method of preserving vagal motor fibers.

In a case report, vagal sensory fibers were mapped and continuously monitored intraoperatively during high vagus schwannoma resection using the laryngeal adductor reflex (LAR). Mapping of nerve fibers on the schwannoma surface enabled identification of sensory fibers. Continuous LAR monitoring during schwannoma subcapsular microsurgical dissection enabled sensory (and motor) vagal fibers to be monitored in real time with excellent postoperative functional outcomes 4).

Outcome

Nerve damage during surgical resection is associated with significant morbidity 5).

This tumour most often presents as a slow growing asymptomatic solitary neck mass, which rarely undergoes malignant transformation.

Literature review

In a comprehensive literature review on 197 articles reporting 235 cases of cervical vagal schwannomas. Presenting symptoms, treatment approach, and postoperative outcomes were recorded and analyzed.

Vagal schwannomas commonly present as asymptomatic neck masses. When they become symptomatic, surgical resection is the standard of care. Gross total resection is associated with higher postoperative morbidity compared to subtotal resection. Initial reports using intraoperative nerve monitoring have shown improved nerve preservation. Recurrence rates are low.

The combination of intermittent nerve mapping with novel continuous vagal nerve monitoring techniques may reduce postoperative morbidity and could represent the future standard of care for vagal schwannoma treatment 6).

Case series

Case series of three patients who underwent vagal schwannoma excision utilizing a IONM technique. The recurrent laryngeal and vagus nerves were monitored via the laryngeal adductor reflex (LAR) using an electromyographic endotracheal tube.

Three patients with suspected vagal schwannomas were treated surgically using the intracapsular enucleation approach with a combination of intermittent IONM and continuous IONM of the LAR.

This combination of continuous and intermittent IONM can be used to preserve vagal laryngeal innervation and function and may represent the future standard of care for vagal schwannoma excision 7).

Green et al. reported 36 of these rare neoplasms in 35 patients. The majority of the tumors presented as a mass in the upper cervical or parapharyngeal region. Usually the mass was asymptomatic. The following types and frequencies of neoplasms of the vagus nerve were noted: paragangliomas, 50%; neurilemmomas, 31%; neurofibromas, 14%; and neurofibrosarcomas, 6%. Surgical resection, with preservation of the vagus nerve when possible, is the treatment of choice. The clinical features, diagnosis, management, and prognosis of the tumors are presented. Special problems that occur with vagal neoplasms include postoperative dysfunction, catecholamine secretion, and intracranial or skull-base extension 8).

Case reports

In a case report, vagal sensory fibers were mapped and continuously monitored intraoperatively during high vagus schwannoma resection using the laryngeal adductor reflex (LAR). Mapping of nerve fibers on the schwannoma surface enabled identification of sensory fibers. Continuous LAR monitoring during schwannoma subcapsular microsurgical dissection enabled sensory (and motor) vagal fibers to be monitored in real time with excellent postoperative functional outcomes 9).

Keshelava et al. operated one patient for cervical schwannoma causing internal carotid artery (ICA) compression.

The patient underwent en bloc excision via transcervical approach under general anesthesia. Pathological examination demonstrated the diagnosis of schwannoma.

This case shows that VNS can cause ICA compression and therefore brain ischemia 10).

Schwam et al. reported a purely intracranial vagal schwannoma 11).

2018

A 60-year-old female patient was seen at our service for a slow-growing, 9 × 6 cm left-sided cystic neck mass. Preoperative clinical and computed tomography evaluation suggested a diagnosis of a lateral neck cyst. The surgical exploration through the lateral cervicotomy revealed a large cystic mass and clearly identified that the tumor was originating from the left vagal nerve. The histopathologic analysis confirmed the diagnosis of schwannoma. Although uncommon, vagal schwannoma with pronounced cystic component should be included in the differential diagnosis of the cystic neck swellings 12).

A 55-year-old woman who presented to the clinic complaining of throat irritation and feeling of something stuck in her throat for the past three months. On examination, a bulging left parapharyngeal mass was noted, displacing the left tonsil and uvula medially. A contrast-enhanced computed tomography (CT) scan of the neck showed a large, hypervascular soft tissue mass with splaying of the left internal carotid artery. Intraoperatively, the tumor was found to be arising from the vagus nerve. Macroscopic surgical pathology examination showed a tan-red, ovoid, and firm mass. Histopathology showed a benign spindle cell tumor with Antoni A areas with palisading cell nuclei and some degenerative change, confirming the diagnosis of vagus nerve schwannoma. CONCLUSIONS Vagus nerve schwannomas should be distinguished from other tumors that arise in the neck before planning surgery, to minimize the risk of nerve injury. Physicians need to be aware of the differential diagnosis of a neck mass, investigations required, the surgical treatment and the potential postoperative complications 13).

Sreevatsa et al. described three cases of schwannoma involving the vagus who presented differently to our unit during past 5 years 14).

A large vagal neurilemmoma in a 33-year-old man is reported. He complained of slowly progressive palsy of the tongue on the left side. Weakness of soft palate movement was also noted. Magnetic resonance imaging (MRI) revealed a tumour in the left parapharyngeal space with partial extension to the posterior cranial fossa through the jugular foramen. Carotid angiography revealed avascularity of the tumour and anterior shift of the left internal carotid artery. The venous phase showed no blood flow in the internal jugular vein. The tumour was successfully extirpated via a transmandibular transpterygoid approach. Although vagus nerve dysfunction was not observed pre-operatively, the tumour was identified as a neurilemmoma arising from the vagus nerve. The surgical approach should be selected according to the lesion in individual patients. Since neurilemmoma is benign in nature, minimal post-operative sequelae should be expected 15).

References

1)

Mierzwiński J, Wrukowska I, Tyra J, Paczkowski D, Szcześniak T, Haber K. Diagnosis and management of pediatric cervical vagal schwannoma. Int J Pediatr Otorhinolaryngol. 2018 Nov;114:9-14. doi: 10.1016/j.ijporl.2018.08.021. Epub 2018 Aug 23. PubMed PMID: 30262374.
2) , 13)

Ramdass AA, Yao M, Natarajan S, Bakshi PK. A Rare Case of Vagus Nerve Schwannoma Presenting as a Neck Mass. Am J Case Rep. 2017 Aug 21;18:908-911. PubMed PMID: 28824161; PubMed Central PMCID: PMC5574523.
3)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227827/
4) , 9)

Sinclair CF, Téllez MJ, Sánchez Roldán MA, Urken M, Ulkatan S. Intraoperative mapping and monitoring of sensory vagal fibers during vagal schwannoma resection. Laryngoscope. 2019 Dec;129(12):E434-E436. doi: 10.1002/lary.28147. Epub 2019 Jun 18. PubMed PMID: 31211430.
5) , 7)

Sandler ML, Sims JR, Sinclair C, Ho R, Yue LE, Téllez MJ, Ulkatan S, Khorsandi AS, Brandwein-Weber M, Urken ML. A novel approach to neurologic function sparing surgical management of vagal schwannomas: Continuous intraoperative nerve monitoring of the laryngeal adductor reflex. Head Neck. 2019 Sep;41(9):E146-E152. doi: 10.1002/hed.25793. Epub 2019 May 6. PubMed PMID: 31058386.
6)

Sandler ML, Sims JR, Sinclair C, Sharif KF, Ho R, Yue LE, Téllez MJ, Ulkatan S, Khorsandi AS, Brandwein-Weber M, Urken ML. Vagal schwannomas of the head and neck: A comprehensive review and a novel approach to preserving vocal cord innervation and function. Head Neck. 2019 Jul;41(7):2450-2466. doi: 10.1002/hed.25758. Epub 2019 Apr 7. Review. PubMed PMID: 30957342.
8)

Green JD Jr, Olsen KD, DeSanto LW, Scheithauer BW. Neoplasms of the vagus nerve. Laryngoscope. 1988 Jun;98(6 Pt 1):648-54. PubMed PMID: 2836676.
10)

Keshelava G, Robakidze Z. Cervical Vagal Schwannoma Causing Asymptomatic Internal Carotid Artery Compression. Ann Vasc Surg. 2019 Oct 17. pii: S0890-5096(19)30859-3. doi: 10.1016/j.avsg.2019.09.021. [Epub ahead of print] PubMed PMID: 31629844.
11)

Schwam ZG, Kaul VZ, Shrivastava R, Wanna GB. Purely intracranial vagal schwannoma: A case report of a rare lesion. Am J Otolaryngol. 2019 May – Jun;40(3):443-444. doi: 10.1016/j.amjoto.2019.02.011. Epub 2019 Feb 18. PubMed PMID: 30799212.
12)

Cukic O, Jovanovic MB. Vagus Nerve Schwannoma Mimicking a Lateral Neck Cyst. J Craniofac Surg. 2018 Nov;29(8):e827-e828. doi: 10.1097/SCS.0000000000005006. PubMed PMID: 30320693.
14)

Sreevatsa MR, Srinivasarao RV. Three cases of vagal nerve schwannoma and review of literature. Indian J Otolaryngol Head Neck Surg. 2011 Oct;63(4):310-2. Epub 2011 Apr 8. PubMed PMID: 23024932; PubMed Central PMCID: PMC3227827.
15)

Yumoto E, Nakamura K, Mori T, Yanagihara N. Parapharyngeal vagal neurilemmoma extending to the jugular foramen. J Laryngol Otol. 1996 May;110(5):485-9. PubMed PMID: 8762326.

Plexiform neurofibroma treatment

Plexiform neurofibroma treatment

Since plexiform neurofibromas are a major cause of the burden of disease and may also progress to malignancy, many efforts have been undertaken to find a cure for these tumors. However, neither surgery nor medication has so far produced a breakthrough therapeutic success.

Plexiform neurofibromas with sizable intraspinal extensions and resultant spinal cord compromise pose challenging management problems, because these lesions may involve multiple nerves and engulf adjacent vascular and visceral structures 1).

Decisions about surgical treatment and frequency of follow-up must be made judiciously and individualized for each patient 2).

Plexiform neurofibromas arising in the orbito-temporal area pose a greater challenge due to its critical function and cosmetic importance of the face. Such plexiform neurofibromas, separately designated as orbito-temporal plexiform neurofibromas, show complex symptoms such as severe ptosis, ectropion, lacrimal gland dysfunction, and even vision loss 3).

A clinical phase I study reported significant shrinkage of plexiform neurofibromas following treatment with the MEK inhibitor selumetinib.

Vaassen et al., reported an 11-year-old NF1 patient with a large plexiform neurofibroma of the neck that had led to a sharp-angled kinking of the cervical spine and subsequent myelopathy. Although surgical stabilization of the cervical vertebral column was urgently recommended, the vertebral column was inaccessible due to extensive tumor growth. In this situation, treatment with the MEK inhibitor trametinib was initiated which resulted in a 22% reduction in tumor volume after 6 months of therapy and finally enabled surgery. These data show that MEK inhibitors may not lead to complete disappearance of NF1-associated plexiform neurofibromas but can be an essential step in a multimodal therapeutic approach for these tumors. The course of our patient suggests that MEK inhibitors are likely to play a significant role in providing a cure for one of the most devastating manifestations of NF1 4).

References

1)

Pollack IF, Colak A, Fitz C, Wiener E, Moreland M, Mulvihill JJ. Surgical management of spinal cord compression from plexiform neurofibromas in patients with neurofibromatosis 1. Neurosurgery. 1998 Aug;43(2):248-55; discussion 255-6. PubMed PMID: 9696077.
2)

Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA. 1997 Jul 2;278(1):51-7. Review. PubMed PMID: 9207339.
3)

Choi J, Choi HJ, Kang KJ, Kwon H, Shin J. Simultaneous Forehead Lift and Blepharoplasty Techniques in Management of Orbito-Temporal Plexiform Neurofibroma. J Craniofac Surg. 2019 Mar 14. doi: 10.1097/SCS.0000000000005448. [Epub ahead of print] PubMed PMID: 30889063.
4)

Vaassen P, Dürr N, Röhrig A, Willing R, Rosenbaum T. Trametinib Induces Neurofibroma Shrinkage and Enables Surgery. Neuropediatrics. 2019 May 29. doi: 10.1055/s-0039-1691830. [Epub ahead of print] PubMed PMID: 31141829.

Motocross accident

Motocross accident

Motocross is a form of off-road motorcycle racing held on enclosed off-road circuits. The sportevolved from motorcycle trials competitions held in the United Kingdom.

Motocross is a physically demanding sport held in all-weather conditions.

They have been gaining popularity among children and adolescents, raising concerns for increased risk of concussions in participating youth.

A 25-year-old man sustained a right-sided brachial plexus injury from a high-velocity motocross accident. Physical examination and electromyography were consistent with a pan-brachial plexopathy with no evidence of axonal continuity. The patient underwent a spinal accessory nerve to suprascapular nerve transfer and an intercostal nerve to musculocutaneous nerve transfer with interpositional sural nerve grafts. He recovered MRC 4/5 elbow flexion and MRC 2/5 shoulder abduction and external rotation. Twenty-two months post-injury the patient displayed a flicker of flexion of his flexor pollicis longus and flexor digitorum profundus to his index finger – he went on to recover a functional pinch. Thirty-six months post-injury the patient displayed a flicker of contraction in brachioradialis with motor unit potentials on electromyography. This case demonstrates that some patients may have capacity for functional recovery after prolonged denervation and highlights the potential impact of anatomical anomalies in the assessment and treatment of peripheral nerve injuries 1).

A 25-year-old man had a T11–T12 fracture dislocation sustained in a motocross accident that resulted in a T11 American Spinal Injury Association Impairment Scale (ASIA) grade A traumatic spinal cord injury. He was treated with acute surgical decompression and spinal fixation with fusion, and enrolled in the spinal scaffold study. A 2 × 10 mm bioresorbable scaffold was placed in the spinal cord parenchyma at T12. The scaffold was implanted directly into the traumatic cavity within the spinal cord through a dorsal root entry zone myelotomy at the caudal extent of the contused area. By 3 months, his neurological examination improved to an L1 AIS grade C incomplete injury. At 6-month postoperative follow-up, there were no procedural complications or apparent safety issues related to the scaffold implantation.

Although longer-term follow-up and investigation are required, this case demonstrates that a polymer scaffold can be safely implanted into an acutely contused spinal cord. This is the first human surgical implantation, and future outcomes of other patients in this clinical trial will better elucidate the safety and possible efficacy profile of the scaffold 2).

Nearly half of all motocross competitors under the age of 18 reported concussion symptoms. Preventive measures are necessary to limit the negative impact from concussions. The risk of concussive injury can be decreased for pediatric motocross riders if they receive professional help with proper helmet fitting and through implementation of stricter guidelines regarding sponsorship 3).

Daniels et al. found a high occurrence of head injuries following pediatric off-road motorcycle riding or motocross accidents despite the use of helmets. Additionally, this study severely underestimates the rate of mild TBIs in this patient population. Our data indicate that motocross is a high-risk sport despite the use of protective gear. Riders and parents should be counseled accordingly about the risks prior to participation 4).

Increased degenerative changes in the cervical and thoracic spine were identified in adolescent motocross racers compared with age-matched controls. The long-term consequences of these changes are unknown; however, athletes and parents should be counseled accordingly about participation in motocross activities 5).

References

1)

Head LK, Wolff G, Boyd KU. Reinnervation of Extrinsic Finger Flexors and Brachioradialis 22 and 36 Months Following Traumatic Pan-Brachial Plexopathy: A Case Report. J Hand Surg Asian Pac Vol. 2019 Mar;24(1):118-122. doi: 10.1142/S2424835519720081. PubMed PMID: 30760136.
2)

Theodore N, Hlubek R, Danielson J, Neff K, Vaickus L, Ulich TR, Ropper AE. First Human Implantation of a Bioresorbable Polymer Scaffold for Acute Traumatic Spinal Cord Injury: A Clinical Pilot Study for Safety and Feasibility. Neurosurgery. 2016 Aug;79(2):E305-12. doi: 10.1227/NEU.0000000000001283. PubMed PMID: 27309344.
3)

Luo TD, Clarke MJ, Zimmerman AK, Quinn M, Daniels DJ, McIntosh AL. Concussion symptoms in youth motocross riders: a prospective, observational study. J Neurosurg Pediatr. 2015 Mar;15(3):255-60. doi: 10.3171/2014.11.PEDS14127. Epub 2015 Jan 2. PubMed PMID: 25555121.
4)

Daniels DJ, Clarke MJ, Puffer R, Luo TD, McIntosh AL, Wetjen NM. High occurrence of head and spine injuries in the pediatric population following motocross accidents. J Neurosurg Pediatr. 2015 Mar;15(3):261-5. doi: 10.3171/2014.9.PEDS14149. Epub 2015 Jan 2. PubMed PMID: 25555116.
5)

Daniels DJ, Luo TD, Puffer R, McIntosh AL, Larson AN, Wetjen NM, Clarke MJ. Degenerative changes in adolescent spines: a comparison of motocross racers and age-matched controls. J Neurosurg Pediatr. 2015 Mar;15(3):266-71. doi: 10.3171/2014.9.PEDS14153. Epub 2015 Jan 2. PubMed PMID: 25555120.