Amyotrophic lateral sclerosis treatment

Amyotrophic lateral sclerosis treatment

Much of care is directed towards minimizing disability:

1. risk of aspiration may be reduced with

a) tracheostomy

b) gastrostomy tube to allow continued feeding

c) vocal cord injection with Teflon

2. noninvasive ventilation: e.g. BiPAP spasticity that occurs when upper motor neuron deficits pre- dominate may be treated (usually with short-lived response) with:

a) baclofen: also may relieve the commonly occurring cramps b) diazepam

3. riluzole (Rilutek®): inhibits presynaptic release of glutamate. Doses of 50-200 mg/d increases tracheostomy-free survival at 9 &12 months,but the improvement is more modest or may be non- existent by ≈ 18 months 1) 2).


The main objective of a phase I trial was to assess the feasibility and safety of microtransplanting human neural stem cell (hNSC) lines into the spinal cord of patients with amyotrophic lateral sclerosis (ALS). Eighteen patients with a definite diagnosis of ALS received microinjections of hNSCs into the gray matter tracts of the lumbar or cervical spinal cord. Patients were monitored before and after transplantation by clinical, psychological, neuroradiological, and neurophysiological assessment. For up to 60  months after surgery, none of the patients manifested severe adverse effects or increased disease progression because of the treatment. Eleven patients died, and two underwent tracheotomy as a result of the natural history of the disease.

They detected a transitory decrease in progression of ALS Functional Rating Scale Revised, starting within the first month after surgery and up to 4 months after transplantation. The results show that transplantation of hNSC is a safe procedure that causes no major deleterious effects over the short or long term. This study is the first example of medical transplantation of a highly standardized cell drug product, which can be reproducibly and stably expanded ex vivo, comprising hNSC that are not immortalized, and are derived from the forebrain of the same two donors throughout this entire study as well as across future trials. This experimental design provides benefits in terms of enhancing both intra- and interstudy reproducibility and homogeneity. Given the potential therapeutic effects of the hNSCs, this observations support undertaking future phase II clinical studies in which increased cell dosages are studied in larger cohorts of patients 3).

References

1)

Bensimon G,Lacomblez L,Meininger V,et al.A Controlled Trial of Riluzole in Amyotrophic Lateral Sclerosis. N Engl J Med. 1994; 24:585–591
2)

Lacomblez L, Bensimon G, Guillet P, et al. Riluzole: A Double-Blind Randomized Placebo-Controlled Dose-Range Study in Amyotrophic Lateral Sclerosis (ALS). Electroenceph Clin Neurophysiol. 1995; 97
3)

Mazzini L, Gelati M, Profico DC, Sorarù G, Ferrari D, Copetti M, Muzi G, Ricciolini C, Carletti S, Giorgi C, Spera C, Frondizi D, Masiero S, Stecco A, Cisari C, Bersano E, Marchi F, Sarnelli MF, Querin G, Cantello R, Petruzzelli F, Maglione A, Zalfa C, Binda E, Visioli A, Trombetta D, Torres B, Bernardini L, Gaiani A, Massara M, Paolucci S, Boulis NM, Vescovi AL; ALS-NSCs Trial Study Group. Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome. Stem Cells Transl Med. 2019 May 18. doi: 10.1002/sctm.18-0154. [Epub ahead of print] PubMed PMID: 31104357.

Lateral lumbar interbody fusion (LLIF)

Lateral lumbar interbody fusion (LLIF)

E.g. XLIFDLIFOLIF. Approach through psoas muscle (XLIF, DLIF) or anterior to psoas muscle (OLIF) through a lateral or anterolateral approach. Can distract the vertebral bodies by increasing the height of the disc space and thereby indirectly decompressing the neural elements. If bone quality is good, and there is no instability nor spondylolisthesis > Grade I, a standalone procedure (i.e. without screw instrumentation) may be an option if cage width of at least 22 mm (or preferably 26 mm) in the AP dimension is used.

LLIF was more effective than TLIF for spondylolisthesis reduction, likely due to the higher profile cage and ligamentotactic effect. In addition, LLIF showed mechanical stability of the reduction level by using a cage with a larger footprint. Therefore, LLIF should be considered a surgical option before TLIF for patients with unstable DS 1).

Advantages

Lateral lumbar interbody fusion (LLIF) is a minimally invasive technique first described by Ozgur et al. 2). LLIF allows the surgeon to access the intervertebral space via a minimally invasive direct lateral approach through the psoas muscle. The advantage of LLIF over the traditional anterior approach is the avoidance of exposure of the abdominal viscera, large vessels, and sympathetic plexus. Injury to the nerve roots and dura, and perineural fibrosis, which can occur after PLIF or TLIF, are minimized with this technique 3)4).

Indications

Used to treat leg pain or back pain generally caused by degenerative disc disease.

LLIF has been utilized to treat a variety of pathologies including adult degenerative scoliosis, central and foraminal stenosis, spondylolisthesis, and adjacent segment degeneration

They have become an increasingly popular surgical technique due to the benefits of minimal tissue disruption, excellent disc visualization, ability to insert a large intervertebral cage to lessen subsidence, and faster recovery times 5) 6).

Position

The LLIF procedure differs from other lumbar procedures in that the patient is positioned in the lateral decubitus position, often times utilizing bending the bed near the iliac crest region in order to facilitate access to the L4-5 disc space.

In awake volunteers, the pressure at the iliac crest or greater trochanter at the break of the bed increases by increasing the bed angle. Women with a lower BMI had high VAS pain scores when their greater trochanter was at maximal bed break. Men with higher BMI had high VAS pain scores when their iliac crest was at maximal bed break. An awareness of the iliac crest or greater trochanter at the break of the bed should be considered to prevent pain and increased pressure based on the patient’s sex and BMI 7).

As with most minimally invasive spine procedures, lateral lumbar interbody fusion (LLIF) requires the use of biplanar fluoroscopy for localization and safe interbody cage placement. Computed tomography (CT)-based intraoperative spinal navigation has been shown to be more effective than fluoroscopic guidance for posterior-based approaches such as pedicle screw instrumentation.

Use of an intraoperative cone-beam CT with an image-guided navigation system is feasible and safe and appears to be accurate, although a larger study is required to confirm these results 8).

Complications

Cost effectiveness

TLIF and LLIF produced equivalent 2-year patient outcomes at an equivalent cost-effectiveness profile 9).

Systematic reviews

Transpsoas lateral interbody fusion is one of the Lateral Lumbar Interbody Fusion minimally invasive approaches for lumbar spine surgery. Most surgeons insert the interbody cage laterally and then insert pedicle or cortical screw and rod instrumentation posteriorly. However, standalone cages have also been used to avoid posterior instrumentation.

The literature on comparison of the two approaches is sparse.

Alvi et al., performed a systematic review and meta-analysis of the available literature on transpsoas lateral interbody fusion by an electronic search of the PubMedEMBASE, and Scopus databases using PRISMA guidelines. They compared patients undergoing transpsoas standalone fusion (TP) with those undergoing transpsoas fusion with posterior instrumentation (TPP).

A total of 28 studies with 1462 patients were included. Three hundred and seventy-four patients underwent TPP, and 956 patients underwent TP. The mean patient age ranged from 45.7 to 68 years in the TP group, and 50 to 67.7 years in the TPP group. The incidence of reoperation was found to be higher for TP (0.08, 95% confidence interval [CI] 0.04-0.11) compared to TPP (0.03, 95% CI 0.01-0.06; p = 0.057). Similarly, the incidence of cage movement was found to be greater in TP (0.18, 95% CI 0.10-0.26) compared to TPP (0.03, 95% CI 0.00-0.05; p < 0.001). Oswestry Disability Index (ODI) and visual analog scale (VAS) scores and postoperative transient deficits were found to be comparable between the two groups.

These results appear to suggest that addition of posterior instrumentation to transpsoas fusion is associated with decreased reoperations and cage movements. The results of previous systematic reviews and meta-analysis should be reevaluated in light of these results, which seem to suggest that higher reoperation and subsidence rates may be due to the use of the standalone technique 10).


A systematic and critical review of recent literature was conducted in accordance with PRISMA guidelines. The sources of the data were PubMed, MEDLINE, Embase, Cochrane and Scopus. Key search terms were “transpsoas”, “interbody fusion”, “LLIF”, “XLIF” and “spondylolisthesis”. Papers included in the review were original research articles in peer-reviewed journals. The articles were thoroughly examined and compared on the basis of study design, outcomes, and results. Only studies which met the eligibility criteria were included. Eight studies were included in the qualitative and quantitative analysis (three retrospective, four prospective, one randomized controlled trial). A total of 308 patients (227 females) (pooled age 64.5 years) and a total of 353 operated levels were analyzed. Mean follow up time ranged from 6.2 to 24 months. There were no reported cases of durotomies or pseudarthrosis in any study. All neurologic complications were reported to be transient with no permanent deficits. Mean improvement in ODI scores ranged between 19.5 (38.6%) to 36 (54.5%). Mean improvement in slip ranged from 47 to 67.5%. Three studies also reported that patient satisfaction and willingness to undergo the procedure again approached 90%. Minimally invasive transpsoas interbody fusion possibly leads to favorable clinical and radiological outcomes while avoiding the possible complications of its more traditional open and minimally invasive counterparts. Further studies are needed to better establish its role in the management of low grade degenerative lumbar spondylolisthesis 11).

Case series

References

1)

Ko MJ, Park SW, Kim YB. Correction of Spondylolisthesis by Lateral Lumbar Interbody Fusion Compared with Transforaminal Lumbar Interbody Fusion at L4-5. J Korean Neurosurg Soc. 2019 May 8. doi: 10.3340/jkns.2018.0143. [Epub ahead of print] PubMed PMID: 31064044.
2) , 3)

Ozgur BM, Aryan HE, Pimenta L, Taylor WR. Extreme lateral interbody fusion (XLIF): a novel surgical technique for anterior lumbar interbody fusion. Spine J. 2006;6:435–443.
4)

Rodgers WB, Gerber EJ, Patterson J. Intraoperative and early postoperative complications in extreme lateral interbody fusion: an analysis of 600 cases. Spine (Phila Pa 1976) 2011;36:26–32.
5)

Rodgers WB, Gerber EJ. Outcomes of MIS spinal fusion: 12 and 24 months. The Spine Journal. 2010;10(9):S141.
6)

Isaacs RE, Hyde J, Goodrich JA, et al. A prospective, nonrandomized, multicenter evaluation of extreme lateral interbody fusion of the treatment of adult degenerative scoliosis: perioperative outcomes and complications. Spine. 2010;15(35):S322–30.
7)

Tatsumi RL. Lateral Pressure and VAS Pain Score Analysis for the Lateral Lumbar Interbody Fusion Procedure. Int J Spine Surg. 2015 Sep 28;9:48. doi: 10.14444/2048. eCollection 2015. PubMed PMID: 26512342; PubMed Central PMCID: PMC4610324.
8)

Park P. Three-Dimensional Computed Tomography-Based Spinal Navigation in Minimally Invasive Lateral Lumbar Interbody Fusion: Feasibility, Technique, and Initial Results. Neurosurgery. 2015 Mar 23. [Epub ahead of print] PubMed PMID: 25812070.
9)

Gandhoke GS, Shin HM, Chang YF, Tempel Z, Gerszten PC, Okonkwo DO, Kanter AS. A Cost-Effectiveness Comparison Between Open Transforaminal and Minimally Invasive Lateral Lumbar Interbody Fusions Using the Incremental Cost-Effectiveness Ratio at 2-Year Follow-up. Neurosurgery. 2016 Apr;78(4):585-95. doi: 10.1227/NEU.0000000000001196. PubMed PMID: 26726969.
10)

Alvi MA, Alkhataybeh R, Wahood W, Kerezoudis P, Goncalves S, Murad MH, Bydon M. The impact of adding posterior instrumentation to transpsoas lateral fusion: a systematic review and meta-analysis. J Neurosurg Spine. 2018 Oct 1:1-11. doi: 10.3171/2018.7.SPINE18385. [Epub ahead of print] Review. PubMed PMID: 30485206.
11)

Goyal A, Kerezoudis P, Alvi MA, Goncalves S, Bydon M. Outcomes following minimally invasive lateral transpsoas interbody fusion for degenerative low grade lumbar spondylolisthesis: A systematic review. Clin Neurol Neurosurg. 2018 Apr;167:122-128. doi: 10.1016/j.clineuro.2018.02.020. Epub 2018 Feb 16. Review. PubMed PMID: 29476935.

Extreme lateral supracerebellar infratentorial approach

Extreme lateral supracerebellar infratentorial approach

Since the first report of application of the extreme lateral supracerebellar infratentorial (ELSI) approach in resecting the posterolateral pontomesencephalic junction (PMJ) region lesions in 2000, few articles concerning the ELSI approach have been published. A review of Chen et al., provided an intimate introduction of the ELSI approach, and evaluated it in facets of patient position, skin incision, craniectomy, draining veins, retraction against the cerebellum, exposure limits, patient healing, as well as advantages and limitations compared with other approaches. The ELSI approach is proposed to be a very young and promising approach to access the lesions of posterolateral PMJ region and the posterolateral tentorial gap. Besides, it has several advantages such as having a shorter surgical pathway, causing less surgical complications, labor-saving, etc. 1).

The extreme lateral supracerebellar infratentorial approach differs from the midline and paramedian supracerebellar infratentorial variants in the area of exposure, patient positioning, and location of the craniotomy. The technique is effective for approaching the posterolateral mesencephalon2).

The extreme-lateral corridor widens the exposure of the paramedian approach to include the anterolateral brainstem surface, offering a complete view of the cisternal space surrounding the middle incisural space 3). It provided visualization of the ambient and tentorial segments of the trochlear nerve 4).

It was initially proposed to treat lesions of the posterolateral surface of the pons principally cavernomas. The versatility of the approach allowed its use for other pathologies like gliomas, aneurysms, epidermoids, and meningiomas 5).

All the extreme-lateral supracerebellar infratentorial (SCIT) approaches warrant a safe route to the quadrigeminal plate. Among the different variants, the median approach had the smallest median surgical area exposure but presented superior results to access the intercollicular safe entry zone 6).

Lesions located at the lateral midbrain surface are better approached through the lateral mesencephalic sulcus (LMS). The goal of a study was to compare the surgical exposure to the LMS provided by the subtemporal approach and the paramedian and extreme-lateral variants of the supracerebellar infratentorial approach.

These 3 approaches were used in 10 cadaveric heads.

Cavalcanti et al., performed measurements of predetermined points by using a neuronavigation system. Areas of microsurgical exposure and angles of the approaches were determined. Statistical analysis was performed to identify significant differences in the respective exposures.

The surgical exposure was similar for the different approaches-369.8 ± 70.1 mm2 for the ST; 341.2 ± 71.2 mm2 for the SCIT paramedian variant; and 312.0 ± 79.3 mm2 for the SCIT extreme-lateral variant (p = 0.13). However, the vertical angular exposure was 16.3° ± 3.6° for the ST, 19.4° ± 3.4° for the SCIT paramedian variant, and 25.1° ± 3.3° for the SCIT extreme-lateral variant craniotomy (p < 0.001). The horizontal angular exposure was 45.2° ± 6.3° for the ST, 35.6° ± 2.9° for the SCIT paramedian variant, and 45.5° ± 6.6° for the SCIT extreme-lateral variant opening, presenting no difference between the ST and extreme-lateral variant (p = 0.92), but both were superior to the paramedian variant (p < 0.001). Data are expressed as the mean ± SD.

The extreme-lateral SCIT approach had the smaller area of surgical exposure; however, these differences were not statistically significant. The extreme-lateral SCIT approach presented a wider vertical and horizontal angle to the LMS compared to the other craniotomies. Also, it provides a 90° trajectory to the sulcus that facilitates the intraoperative microsurgical technique 7).


Five cavernous malformations, two juvenile pilocytic astrocytomas, and one peripheral superior cerebellar artery aneurysm located in this region were approached in eight patients. In this extreme lateral approach, the sigmoid sinus is unroofed more superiorly and the bone flap includes not only a posterior fossa craniotomy but also a portion that extends just above the transverse sinus. The dural opening is based along the transverse and sigmoid sinuses. After the cerebrospinal fluid has been drained, the lateral aspect of the brainstem is approached via the cerebellar surface. A proximal tentorial incision offers additional rostral exposure where needed.

Seven patients in this series underwent successful resection of their lesion. The remaining patient’s aneurysm was clipped successfully with no major complications.

The extreme lateral supracerebellar infratentorial approach differs from the midline and paramedian supracerebellar infratentorial variants in the area of exposure, patient positioning, and location of the craniotomy. The technique is effective for approaching the posterolateral mesencephalon8).


The extreme lateral infratentorial supracerebellar approach to treat pathologies located in the ambient cistern and posterior incisural space is a technically feasible route in selected cases. In this cadaveric study, we demonstrate the benefits of endoscope-assisted microsurgical maneuvers using the extreme lateral supracerebellar infratentorial approach.

An endoscope-assisted infratentorial supracerebellar approach was performed in six formalin-fixed cadaveric heads using standard microneurosurgical methods. Dissections were performed in a stepwise fashion, comparing the exposure afforded by the microsurgical route alone to the endoscope-assisted route, using 0- and 30-degree angled lenses. Relationships among the target and the surroundings neurovascular structures were described.

Endoscope-assisted maneuvers for the extreme lateral supracerebellar approach provide an improved operative view and have the potential to reduce parenchymal trauma and neurovascular injuries. The endoscopic techniques bring the surgeon to the anatomy, enhancing illumination and surgical visualization.

Direct visualization of the posterior and posterolateral incisural space avoids retraction of the occipital lobe and damage to the deep venous complex. The extreme lateral infratentorial supracerebellar corridor is effective for approaching the posterolateral mesencephalic junction and the posterior incisural space in selected cases. Endoscope-assisted microsurgery can improve visualization and minimize parenchymal retraction, which should enhance surgical control 9).


For endoscopic-controlled approaches, the extreme lateral approach provides the largest surgical freedom when accessing the ipsilateral superior colliculus (P < 0.0001), the lateral approach provides the largest surgical freedom to the pineal gland (P < 0.0001), and the paramedian craniotomy provides the largest surgical freedom when accessing the splenium (P < 0.0001). The extreme lateral approach to the pineal gland provided the largest horizontal angle of attack (P < 0.0001), and the extreme lateral approach to the ipsilateral superior colliculus provided the largest vertical angle of attack (P < 0.001). The microscope provides marginally increased surgical freedom and a better angle of attack to specific anatomical targets in the paramedian and extreme lateral approach compared with those provided by the endoscope, but these differences are negligible during intraoperative application.

Presurgical planning and a detailed understanding of the important neurovascular structures in the pineal region are paramount to safe and successful surgical execution. Our current cadaveric study indicates that the medial-to-lateral location of craniotomy can maximize access to pineal region targets. Furthermore, the endoscope is a viable alternative to the microscope for identifying pathology of the posterior incisura. These differences in surgical freedom and angle of attack to the pineal region may be useful to consider when planning minimal-access approaches 10).

Videos

A video illustrates the case of a 52-year-old man with a history of multiple bleeds from a lateral midbrain cerebral cavernous malformation, who presented with sudden-onset headache, gait instability, and left-sided motor and sensory disturbances. This lesion was eccentric to the right side and was located in the dorsolateral brainstem. Therefore, the lesion was approached via a right-sided extreme lateral supracerebellar infratentorial (exSCIT) craniotomy with monitoring of the cranial nerves. This video demonstrates the utility of the exSCIT for resection of dorsolateral brainstem lesions and how this approach gives the surgeon ready access to the supracerebellar space, and cerebellopontine angle cistern. The lateral mesencephalic safe entry zone can be accessed from this approach; it is identified by the intersection of branches of the superior cerebellar artery and the fourth cranial nerve with the vein of the lateral mesencephalic sulcus. The technique of piecemeal resection of the lesion from the brainstem is presented. Careful patient selection and respect for normal anatomy are of paramount importance in obtaining excellent outcomes in operations within or adjacent to the brainstem. The link to the video can be found at: https://youtu.be/aIw-O2Ryleg 11).

Case series

Five cavernous malformations, two juvenile pilocytic astrocytomas, and one peripheral superior cerebellar artery aneurysm located in this region were approached in eight patients. In this extreme lateral approach, the sigmoid sinus is unroofed more superiorly and the bone flap includes not only a posterior fossa craniotomy but also a portion that extends just above the transverse sinus. The dural opening is based along the transverse and sigmoid sinuses. After the cerebrospinal fluid has been drained, the lateral aspect of the brainstem is approached via the cerebellar surface. A proximal tentorial incision offers additional rostral exposure where needed.

Seven patients in this series underwent successful resection of their lesion. The remaining patient’s aneurysm was clipped successfully with no major complications 12).

References

1)

Chen X, Feng YG, Tang WZ, Li HT, Li ZJ. A young and booming approach: the extreme lateral supracerebellar infratentorial approach. Neurosci Bull. 2010 Dec;26(6):479-85. doi: 10.1007/s12264-010-1036-7. Review. PubMed PMID: 21113199; PubMed Central PMCID: PMC5560335.
2) , 8)

Vishteh AG, David CA, Marciano FF, Coscarella E, Spetzler RF. Extreme lateral supracerebellar infratentorial approach to the posterolateral mesencephalon: technique and clinical experience. Neurosurgery. 2000 Feb;46(2):384-8; discussion 388-9. PubMed PMID: 10690727.
3)

Ammirati M, Bernardo A, Musumeci A, Bricolo A. Comparison of different infratentorial-supracerebellar approaches to the posterior and middle incisural space: a cadaveric study. J Neurosurg. 2002 Oct;97(4):922-8. PubMed PMID: 12405382.
4)

Ammirati M, Musumeci A, Bernardo A, Bricolo A. The microsurgical anatomy of the cisternal segment of the trochlear nerve, as seen through different neurosurgical operative windows. Acta Neurochir (Wien). 2002 Dec;144(12):1323-7. PubMed PMID: 12478346.
5)

Giammattei L, Borsotti F, Daniel RT. Extreme lateral supracerebellar infratentorial approach: how I do it. Acta Neurochir (Wien). 2019 Apr 1. doi: 10.1007/s00701-019-03886-5. [Epub ahead of print] PubMed PMID: 30937609.
6)

Cavalcanti DD, Morais BA, Figueiredo EG, Spetzler RF, Preul MC. Supracerebellar Infratentorial Variant Approaches to the Intercollicular Safe Entry Zone. World Neurosurg. 2019 Feb;122:e1285-e1290. doi: 10.1016/j.wneu.2018.11.033. Epub 2018 Nov 14. PubMed PMID: 30447444.
7)

Cavalcanti DD, Morais BA, Figueiredo EG, Spetzler RF, Preul MC. Surgical approaches for the lateral mesencephalic sulcus. J Neurosurg. 2019 Apr 12:1-6. doi: 10.3171/2019.1.JNS182036. [Epub ahead of print] PubMed PMID: 30978690.
9)

Rehder R, Luiz da Costa MP, Al-Mefty O, Cohen AR. Endoscope-Assisted Microsurgical Approach to the Posterior and Posterolateral Incisural Space. World Neurosurg. 2016 Jul;91:210-7. doi: 10.1016/j.wneu.2016.04.017. Epub 2016 Apr 16. PubMed PMID: 27090972.
10)

Zaidi HA, Elhadi AM, Lei T, Preul MC, Little AS, Nakaji P. Minimally Invasive Endoscopic Supracerebellar-Infratentorial Surgery of the Pineal Region: Anatomical Comparison of Four Variant Approaches. World Neurosurg. 2015 Aug;84(2):257-66. doi: 10.1016/j.wneu.2015.03.009. Epub 2015 Mar 28. PubMed PMID: 25827042.
11)

Kalani MYS, Couldwell WT. Extreme Lateral Supracerebellar Infratentorial Approach to the Lateral Midbrain. J Neurol Surg B Skull Base. 2018 Dec;79(Suppl 5):S415-S417. doi: 10.1055/s-0038-1669981. Epub 2018 Sep 25. PubMed PMID: 30456047; PubMed Central PMCID: PMC6240419.
12)

Vishteh AG, David CA, Marciano FF, Coscarella E, Spetzler RF. Extreme lateral supracerebellar infratentorial approach to the posterolateral mesencephalon: technique and clinical experience. Neurosurgery. 2000 Feb;46(2):384-8; discussion 388-9. PubMed PMID: 10690727.
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