Diseased Filum Terminale as a Cause of Tethered Cord Syndrome in Ehlers-Danlos Syndrome: Histopathology, Biomechanics, Clinical Presentation, and Outcome of Filum Excision

Klinge, Petra M.; Srivastava, Vipin; McElroy, Abigail; Leary, Owen P.; Ahmed, Zahra S.; Donahue, John E.; Brinker, Thomas; Vloo, Philippe De; Gokaslan, Ziya L.

doi:10.1016/j.wneu.2022.03.038

Cited by 16 publications

(23 citation statements)

References 28 publications

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“…Some of these mechanical factors may be interrelated. For example, hEDS is frequently associated with occult (functional) cord tethering ( Klinge et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure

Renz‐Polster

Tremblay

Bienzle

et al. 2022

Front. Cell. Neurosci.

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Although myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has a specific and distinctive profile of clinical features, the disease remains an enigma because causal explanation of the pathobiological matrix is lacking. Several potential disease mechanisms have been identified, including immune abnormalities, inflammatory activation, mitochondrial alterations, endothelial and muscular disturbances, cardiovascular anomalies, and dysfunction of the peripheral and central nervous systems. Yet, it remains unclear whether and how these pathways may be related and orchestrated. Here we explore the hypothesis that a common denominator of the pathobiological processes in ME/CFS may be central nervous system dysfunction due to impaired or pathologically reactive neuroglia (astrocytes, microglia and oligodendrocytes). We will test this hypothesis by reviewing, in reference to the current literature, the two most salient and widely accepted features of ME/CFS, and by investigating how these might be linked to dysfunctional neuroglia. From this review we conclude that the multifaceted pathobiology of ME/CFS may be attributable in a unifying manner to neuroglial dysfunction. Because the two key features – post exertional malaise and decreased cerebral blood flow – are also recognized in a subset of patients with post-acute sequelae COVID, we suggest that our findings may also be pertinent to this entity.

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“…Some of these mechanical factors may be interrelated. For example, hEDS is frequently associated with occult (functional) cord tethering ( Klinge et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure

Renz‐Polster

Tremblay

Bienzle

et al. 2022

Front. Cell. Neurosci.

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“…In the adjacent not immobilized upper segments, an increase of sensory nerve endings was observed. 28 Since our prior work has demonstrated that the FT in TCS is subjected to increased mechanical forces, 6 we cannot exclude the possibility that TCS influences the receptor density within the FT. Future anatomical, experimental, and clinical work is needed to investigate this issue.…”

Section: Discussionmentioning

confidence: 99%

“…The comorbidity of connective tissue disorder adds congenital collagen fibril damage. 6 Therefore, this study relies on the investigation of a heavily diseased FT.…”

Section: Discussionmentioning

confidence: 99%

“…All cases were recruited according to a recently reported study protocol, which includes comprehensive neurological, radiological, and urological diagnostics. 6 Since preliminary TEM results revealed sensory nerve endings in the FT of the first 16 patients, the Institutional Review Board protocol was amended to include the recording of paraspinal muscles above and below the surgical level electrostimulation of the FT in addition to the routine intraoperative electrophysiological monitoring for TCS surgery. Ethical approval for the study was obtained under IRB protocol 1107867-10, including informed consent from patients and/or their legal guardians.…”

Section: Methodsmentioning

confidence: 99%

“…1 Today, the FT is seen as an elastic fibrous band that anchors the conus medullaris to the coccyx. 2-6 Still, the neural elements of the FT are commonly understood as embryonic remnants occurring in the conversion of the caudal segments of the human fetal spinal cord into conus and filum. 7…”

mentioning

confidence: 99%

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Not Just an Anchor: The Human Filum Terminale Contains Stretch Sensitive and Nociceptive Nerve Endings and Responds to Electrical Stimulation With Paraspinal Muscle Activation

et al. 2022

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BACKGROUND:Neural components of the fibrous filum terminale (FT) are well known but are considered as embryonic remnants without functionality.OBJECTIVE:To investigate the ultrastructure of human FT specimens for sensory nerve endings and record paraspinal muscle activity on electrostimulation of the FT.METHODS:We prospectively investigated a cohort of 53 patients who underwent excision of the FT for the treatment of tethered cord syndrome. Surgical FT specimens were investigated by light and transmission electron microscopy. Intraoperative electrophysiological routine monitoring was extended by recording paraspinal muscles above and below the laminotomy level.RESULTS:Light microscopy revealed tiny peripheral nerves piercing the pia mater of the FT and entering its fibrous core. Transmission electron microscopy unveiled within the fibrous core of the FT myelinated nerve structures in 8 of the 53 patients and unmyelinated ones in 10 of the 53 patients. Both nerve endings encapsulated in fibrous tissue or unencapsulated nonmyelinated Schwann cell nerve bundles, that is, Remak cells, were found. Those nerve endings resembled mechanoreceptor and nociceptive receptor structures found in human skin, muscle tendons, and skeletal ligaments. Specifically, we found Ruffini mechanoreceptors and in addition nerve endings which resembled nociceptive glioneural structures of the skin. Bipolar electrostimulation of the FT was associated with paraspinal muscle activity above and below the spinal segment at which the FT was stimulated.CONCLUSION:Morphological and electrophysiological results indicate the presence of functional sensory nerve endings in the FT. Like other spine ligaments, the FT may serve as a proprioceptive element but may also contribute to back pain in spine disorders.

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Chiari Malformation Type 1 in Adults

Zisakis

Sun

Pepper

et al. 2023

Advances and Technical Standards in Neurosurgery

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Diseased Filum Terminale as a Cause of Tethered Cord Syndrome in Ehlers-Danlos Syndrome: Histopathology, Biomechanics, Clinical Presentation, and Outcome of Filum Excision

Cited by 16 publications

References 28 publications

The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure

The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure

Not Just an Anchor: The Human Filum Terminale Contains Stretch Sensitive and Nociceptive Nerve Endings and Responds to Electrical Stimulation With Paraspinal Muscle Activation

Chiari Malformation Type 1 in Adults

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