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.

Spinal meningioma treatment

Spinal meningioma treatment

Radical resection of spinal meningiomas can be performed with good functional results. Extensive tumor calcification, especially in elderly patients proved to harbor an increased risk for surgical morbidity 1).


Onken et al., reported on their surgical experience that involves two institutions in which 207 patients underwent surgery for spinal meningiomas (sMNGs) . Special focus was placed on patients with sMNGs localized anterior to the denticulate ligament (aMNGs) that were treated via a unilateral posterior approach (ULPA).

The duration of surgery, extent of resection, and outcomes are comparable between aMNGs and posterior to the denticulate ligament (pMNGs) when removed via a ULPA. Thus, ULPA represents a safe route to achieve a gross-total resection, even in cases of aMNG 2).


Posterior approaches provide adequate exposure to safely remove ventrally located spinal meningioma. Posterior exposures with lateral bone resection, denticulate ligament division, provide also adequate exposure for safe removal 3).

Technique

After dural opening, a plane can be developed between the arachnoid and the tumor. The tumor is then internally debulked using suction, an ultrasonic surgical aspirator, microscissors, or laser.

After debulking, in the majority of cases the tumor can be rolled away from the spinal cord and toward its dural attachment.

The tumor is then removed from its dural attachment.

Dura with remaining tumor can be coagulated using bipolar cauterization or resected.

In the majority of cases, the dural attachment was cauterized rather than resected. The dural attachment was always cauterized in cases involving an anterior dural attachment. Additionally, in most cases the dura was closed primarily, compared with suturing in a graft, which was performed far less frequently

Another option was separation of the dura into an outer and inner layer and to resect the tumor with the inner layer, leaving the outer layer available for closure 4).

Videos

References

1)

Sandalcioglu IE, Hunold A, Müller O, Bassiouni H, Stolke D, Asgari S. Spinal meningiomas: critical review of 131 surgically treated patients. Eur Spine J. 2008 Aug;17(8):1035-41. doi: 10.1007/s00586-008-0685-y. Epub 2008 May 15. PubMed PMID: 18481118; PubMed Central PMCID: PMC2518757.
2)

Onken J, Obermüller K, Staub-Bartelt F, Meyer B, Vajkoczy P, Wostrack M. Surgical management of spinal meningiomas: focus on unilateral posterior approach and anterior localization. J Neurosurg Spine. 2018 Dec 1:1-6. doi: 10.3171/2018.8.SPINE18198. [Epub ahead of print] PubMed PMID: 30544344.
3)

Notani N, Miyazaki M, Kanezaki S, Ishihara T, Kawano M, Tsumura H. Surgical management of ventrally located spinal meningiomas via posterior approach. Eur J Orthop Surg Traumatol. 2017 Feb;27(2):181-186. doi: 10.1007/s00590-016-1860-1. PubMed PMID: 27671472.
4)

Gottfried ON, Gluf W, Quinones-Hinojosa A, Kan P, Schmidt MH. Spinal meningiomas: surgical management and outcome. Neurosurg Focus. 2003 Jun 15;14(6):e2. Review. PubMed PMID: 15669787.

Acromegaly medical treatment

Acromegaly medical treatment

Medical treatment

Indications

Patients not cured by surgery.

Who cannot tolerate surgery.

Recurrence after surgery or radiotherapy.

More satisfactory surgical outcomes for noninvasive macroadenomas treated with presurgical SA may be achieved, although controversy of such adjuvant therapy exists. Combination of SA and pegvisomant or cabergoline shows advantages in some specific cases. Thus, an individual treatment program should be established for each patient under a full evaluation of the risks and benefits 1).


First-generation somatostatin receptor ligands (SRL) are the mainstay of acromegaly treatment, however the percentage of patients controlled with these drugs significantly varies in the different studies. Many factors are involved in the resistance to SRL.

In a review, Gadelha et al., updated the physiology of somatostatin and its receptors (sst), the use of SRL in the treatment of acromegaly and the factors involved in the response to these drugs. The SRL act through interaction with the sst, which up to now have been characterized as five subtypes. The first-generation SRL, octreotide and lanreotide, are considered sst2 specific and have biochemical response rates varying from 20 to 70%. Tumor volume reduction can be found in 36-75% of patients. Several factors may determine the response to these drugs, such as sst, aryl hydrocarbon receptor interacting protein (AIP), E-cadherinZAC1filamin A and β-arrestin expression in the somatotropinomas. In patients resistant to first-generation SRL, alternative medical treatment options include: SRL high dose regimens, SRL in combination with cabergoline or pegvisomant, or the use of pasireotide. Pasireotide is a next-generation SRL with a broader pattern of interaction with sst. In the light of the recent increase of treatment options in acromegaly and the deeper knowledge of the determinants of response to the current first-line therapy, a shift from a trial-and-error treatment to a personalized one could be possible 2).


The cost of treatment including medications and the possibility of major side effects represent important limitations of the medical therapy 3) 4).

The most widely used criteria for neurosurgical outcome assessment were combined measurements of IGF-1 and GH levels after oral glucose tolerance test (OGTT) 3 months after surgery. Ninety-eight percent of respondents stated that primary treatment with somatostatin receptor ligands (SRLs) was indicated at least sometime during the management of acromegaly patients. In nearly all centers (96%), the use of pegvisomant monotherapy was restricted to patients who had failed to achieve biochemical control with SRL therapy. The observation that most centers followed consensus statement recommendations encourages the future utility of these workshops aimed to create uniform management standards for acromegaly 5)

Current pharmacotherapy includes somatostatin analogs (SAs) and GH receptor antagonist; the former consists of lanreotide Autogel (ATG) and octreotide long-acting release (LAR), and the latter refers to pegvisomant. As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of GH and IGF-1 by subcutaneous injection every 4-6 weeks. Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH-secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration. More satisfactory surgical outcomes for noninvasive macroadenomas treated with presurgical SA may be achieved, although controversy of such adjuvant therapy exists. Combination of SA and pegvisomant or cabergoline shows advantages in some specific cases. Thus, an individual treatment program should be established for each patient under a full evaluation of the risks and benefits 6).

Somatostatin treatment can induce extensive fibrosis in GH secreting pituitary adenoma 7).

References

1)

Wang JW, Li Y, Mao ZG, Hu B, Jiang XB, Song BB, Wang X, Zhu YH, Wang HJ. Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas. Patient Prefer Adherence. 2014 Jan 6;8:43-51. eCollection 2014. Review. PubMed PMID: 24421637; PubMed Central PMCID: PMC3888346.
2)

Gadelha MR, Wildemberg LE, Bronstein MD, Gatto F, Ferone D. Somatostatin receptor ligands in the treatment of acromegaly. Pituitary. 2017 Feb;20(1):100-108. doi: 10.1007/s11102-017-0791-0. Review. PubMed PMID: 28176162.
3)

Chanson P, Salenave S, Kamenicky P, Cazabat L, Young J. Pituitary tumours: Acromegaly. Best Pract Res Clin Endocrinol Metab. 2009;23:555–74.
4)

Gondim JA, Ferraz T, Mota I, Studart D, Almeida JP, Gomes E, et al. Outcome of surgical intrasellar growth hormone tumor performed by a pituitary specialist surgeon in a developing country. Surg Neurol. 2009;72:15–9.
5)

Giustina A, Bronstein MD, Casanueva FF, Chanson P, Ghigo E, Ho KK, Klibanski A, Lamberts S, Trainer P, Melmed S. Current management practices for acromegaly: an international survey. Pituitary. 2011 Jun;14(2):125-33. doi: 10.1007/s11102-010-0269-9. PubMed PMID: 21063787.
6)

Wang JW, Li Y, Mao ZG, Hu B, Jiang XB, Song BB, Wang X, Zhu YH, Wang HJ. Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas. Patient Prefer Adherence. 2014 Jan 6;8:43-51. Review. PubMed PMID: 24421637.
7)

Kerschbaumer J, Pinggera D, Moser P, Hofmann A, Thomé C, Freyschlag CF. Somatostatin treatment can induce extensive fibrosis in growth hormone-producing adenoma. Acta Neurochir (Wien). 2016 Mar;158(3):441-3. doi: 10.1007/s00701-016-2714-7. Epub 2016 Jan 23. PubMed PMID: 26801514.
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