Filum Disease Behind Fibromyalgia: A Preliminary Study

doi:10.21203/rs.3.rs-1664731/v1

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Research Article

Filum Disease Behind Fibromyalgia: A Preliminary Study

https://doi.org/10.21203/rs.3.rs-1664731/v1

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Background: To identify a group of patients with fibromyalgia (FM) and filum disease (FD)/neuro-cranio-vertebral syndrome (NCVS). To analyse the clinical and radiological similarities and differences between groups. To evaluate the clinical results in the FM group after sectioning of the filum terminale (SFT) with the Filum System (FS) Method. To propose an aetiopathological mechanism for FM by applying the FD/NCVS theory.

Methods: A retrospective study of 394 patients diagnosed with FD/NCVS. From this sample, two subsamples were created: patients with FM (n=25) and patients without FM (n=369). The incidence of signs and symptoms were compared between groups. The FM group underwent SFT, and the evolution of signs and symptoms were assessed 8 hours, 1 month, and 1 year post-procedure.

Results: 55% of the signs and symptoms assessed were present in similar proportions in both samples. There were also similar radiological findings between groups. There was a significant improvement (p<0.05) in many of the signs and symptoms in the FM group after the sectioning of the filum terminale. There were also radiological signs present in similar proportions, including descent of the cerebellar tonsils, multiple discopathy and syringomyelia.

Conclusions: The overlap of signs and symptoms suggests that the underlying cause for central sensitization may be due to FD in a subgroup of FM patients. Patients with FM experience an amelioration of signs and symptoms after SFT. We propose that doctors approach FM cases with an extensive neurological exam that includes complete imaging to facilitate possible diagnosis of FD/NCVS and subsequent treatment.

Filum disease

fibromyalgia

neuro-cranio-vertebral syndrome

sectioning filum terminale

idiopathic scoliosis

syringomyelia

scoliosis

Arnold-Chiari syndrome I

Fibromyalgia (FM) is a condition with an unknown cause, its main symptom is chronic widespread pain that affects muscles, ligaments, and tendons. People with FM have an increased response to painful stimuli (hyperalgesia) and an altered pain perception, whereby stimuli that are not normally perceived as painful are in fact painful (allodynia). Other clinical manifestations of FM include intense physical and cognitive fatigue, sleep disorders, headaches, muscle contractures, joint stiffness, paresthesia, and mood changes, including depression and anxiety.

Despite ongoing research, the cause and optimal treatment of FM remain unclear. Various physical and emotional factors may play a role in the onset of this disease, where the patient presents chronic and altered pain perception, without an organic cause.

The familial aggregation observed among the relatives of patients with FM suggests that there may be a genetic basis that contributes to the appearance of the disease (1). Although there are people who develop FM without an apparent cause, others experience a series of factors that predispose them to suffer from FM. Contributing factors include: stress, mood disorders, certain infections (Lyme disease or viral diseases), previous known conditions that limit the quality of life (rheumatoid arthritis, systemic lupus erythematosus, etc.), physical or emotional trauma, or sleep disorders.

FM is one of more than 50 diseases encompassed within the central sensitization syndromes, a set of pathologies that have a common pathophysiological origin and biophysiological mechanism. FM, together with chronic fatigue syndrome and multiple chemical sensitivity, are likely the most characteristic diseases of this group. Brain imaging studies in people with FM and related chronic pain disorders have shown changes in brain function and connection between different parts of the brain, as well as abnormal regional cerebral blood flow (2). In FM patients, abnormalities have been identified along the entire pain pathway, from peripheral activation of nociceptors, to changes in neurotransmitters and somatosensory cortical interpretation of the central nervous system (3, 4). Moreover, some studies have shown that cerebral blood flow is reduced in the thalamus and caudate nucleus in patients with FM (5, 6).

Functional imaging studies support the theory that many signs and symptoms of FM may be due to central nervous system (CNS) dysfunction, leading to impaired processing of sensory stimuli. Findings of hypoperfusion in the thalamus and caudate nucleus (5) by single photon emission computed tomography analysis in patients with FM support this hypothesis.

Nevertheless, despite numerous studies published on the neurophysiopathological changes observed in patients with FM, no one has been able to identify the cause of these alterations. The theory of the Filum disease (FD) and the Neuro-cranio-vertebral syndrome (NCVS) may be able to explain the mechanism behind central sensitization in FM.

Filum disease is the result of an abnormal traction exerted on the neuroaxis by the filum terminale (FT) (6, 7, 8). Whereas in Filum disease this traction is congenital, in Neuro-cranio-vertebral syndrome it is acquired. The FT is a ligament of neuroconnective tissue that attaches the conus medullaris to the coccyx. When it presents abnormal tension, it causes a pathological traction on the neuroaxis that can give rise to different pathologies such as Arnold-Chiari Syndrome I (ACSI) (7), idiopathic syringomyelia (ISM) and idiopathic scoliosis (IS). FD is due to an asynchronous growth between the vertebral column and the spinal cord in the embryonic phase, which creates a mechanical conflict exerted by the FT that translates into the classic clinical and radiological manifestations of FD (9, 10).

FM and Filum disease/ Neuro-cranio-vertebral syndrome share several symptoms. Headache, dizziness, paresthesia, muscle weakness, short-term memory loss, difficulty concentrating, sleep disorders, dysesthesia, chronic fatigue, generalized pain, chronic low back pain, mood disorders, and anxiety are some of the symptoms common to both pathologies.

The pathological traction effect exerted by the FT on the neuroaxis could be the cause of central sensitization behind FM, and could explain the pathophysiological changes in the CNS produced by the chronic and progressive traction seen in Filum disease. The minimally invasive surgical intervention of Filum terminale sectioning (SFT) forms part of the Filum System (FS) method developed at the Institut Chiari & Syringomyelia & Scoliosis Barcelona to treat Filum disease/ Neuro-cranio-vertebral syndrome. This Institute is the only centre qualified to apply it worldwide, as a highly specialized private centre holding the Research & Development (R&D) certification 1583.001.16-160920-CER-RD.001 from the Spanish Innovation Certification Agency (ACIE) and ENAC certification 33/C-PR074, Certificate IQNet and AENOR Quality Management System ISO 9001:2015, Registration Number: ES-0081/2015 for the following fields of activities: Research, Diagnosis and Treatment of the Filum Disease and Quality Management Certification according to UNE-EN ISO 9001:2008 standards.

SFT consists of sectioning the filum terminale externum at the level of the sacral hiatus and releasing the end of the dural sac. The procedure is performed under local anesthesia and sedation (unless contraindicated), of short duration (50 minutes), without blood loss, technically simple and with a low rate of complications (local discomfort and skin infection). The objective of this intervention is to eliminate the pathological tension exerted on the neuroaxis and relieve the associated symptoms (11). This technique has led to an immediate improvement in the symptoms of ACSI in most cases, since it eliminates the tension that displaces the cerebellar tonsils and relieves the tension that causes this displacement. An improvement in the signs and symptoms associated with ISM and IS has also been observed, due to the elimination of the tension exerted on the neuroaxis and the mechanism behind said tension (12).

A recent study utilized this surgical technique to treat FM patients, under the assumption that FM may share the same cause as Filum disease (13). Mantia et al. present a series of 20 patients with FM who underwent SFT at our institution with the Filum System (FS) method, and who also followed a physiotherapy program. They compared these results to 18 patients with FM who only underwent physical therapy (13). Their results indicate that FM patients who underwent SFT in conjunction with physical therapy showed significant improvements in symptoms in terms of pain reduction and increased quality of life, compared to the group that refused surgery and only underwent physical therapy. A possible conclusion from this study is that the traction exerted by the FT may be one of the predisposing factors leading to the development of FM, and that the surgical intervention of the SFT may improve the overall treatment of some patients with FM.

The considerable overlap of symptoms between FM and Filum disease/Neuro-cranio-vertebral syndrome suggests a strong relationship between them, and warrants the realization of this study with the following objectives:

1. Selection and description of a group of patients with FM and Filum disease/Neuro-cranio-vertebral syndrome treated at the Institut Chiari & Syringomyelia & Scoliosis Barcelona (ICSEB) from 2015 to 2019.

2. Statistical analysis of the clinical and radiological similarities and differences between both groups.

3. Statistical comparison of the clinical results obtained in the group of patients with Filum disease/Neuro-cranio-vertebral syndrome and confirmed FM after surgical section of the FT using the FS Method.

4. Proposal of an aetiopathological mechanism of FM according to the Filum disease/Neuro-cranio-vertebral syndrome theory.

We conducted a retrospective search from our database between May 18th, 2015, and December 2nd, 2019, and found a total of 394 patients diagnosed with Filum disease/Neuro-cranio-vertebral syndrome, as published in a previous article (14). From this sample of 394 cases, 2 subsamples were created: the Fibromyalgia/Filum disease sample (25 cases with confirmed diagnosis of FM and Filum disease), and the Filum disease sample (369 cases with Filum disease without confirmed FM).

The FM diagnosis was confirmed by following the ACTTION-APS Pain Taxonomy (AAPT) (4) criteria, whereby patients must express pain in at least 6 of 9 specific points, and present moderate or intense sleep disorders or fatigue for at least 3 months. Patients were excluded from the study if they had additional and serious diagnoses that indicated a double surgical intervention in conjunction with SFT, or if the intervention was contraindicated. Patients under 18 years of age were also excluded.

The selection of patients for initial visits at our institution, and the subsequent diagnosis protocol of Filum disease are presented in a previous publication (14). The data collected on the clinical findings (signs, symptoms, imaging) was carried out under the ICSEB standards that are summarized in the previously mentioned article. The FS Method was used to assess signs and symptoms, and MRI and X-ray imaging of the spine followed the parameters outlined in the aforementioned publication (14). See Additional file 1 for a table with the 25 cases that make up the sample of patients with FM and Filum disease, and includes the date of the intervention as well as the preoperative signs and symptoms. Of the 25 cases from the Fibromyalgia/Filum disease sample, 24 cases were assessed 8 hours after the intervention, 19 cases a month after the intervention, and 12 cases a year after the intervention. The patients´ ethnicity and country of origin were self-reported in an open-ended questionnaire.

For the data analysis, general data, symptoms, clinical signs, and imaging results were obtained from all patients. Data was collected from a digital database (FileMaker Pro Advanced 11.0v2, FileMaker, Inc. Santa Clara, CA, USA), from which it was exported first to a Microsoft Excel 2011 spreadsheet for Mac version 14.1.0 (Microsoft Corporation, Redmond, WA, USA), and then to SPSS version 21 (IBM Corporation, Armonk, NY, USA). Demographic data, symptoms, signs, and imaging results are presented as mean ± standard deviation. Normality of the data distribution was defined using the Kolmogorov-Smirnov test (Saphiro-Wilk test). The analysis of the postoperative results was done by comparing the findings with a t-test for paired samples (p < 0.05). The correlation of the signs, symptoms, and imaging results between patients in the Fibromyalgia/Filum disease sample and the Filum disease sample was carried out with a linear regression that also considered sex and age. Pearson’s correlation was also utilized, as well as a t-test for independent samples. Missing data was handled with pairwise deletion.

From the sample of 394 patients diagnosed with Filum disease/Neuro-cranio-vertebral syndrome, two subsamples were created. The Fibromyalgia/Filum disease sample, consisting of 25 patients with confirmed FM and Filum disease, with a mean age of 38 years, 88% of which were female patients and 12% were male patients. And the Filum disease sample, with 369 patients diagnosed with Filum disease/Neuro-cranio-vertebral syndrome without confirmed FM, with a mean age of 34 years, 72% of which were female patients and 28% of which were male patients. When comparing the prevalence of signs and symptoms in both subsamples, 55% were present in similar proportions in both groups (linear regression, p < 0.05). These results are presented in Fig. 1. The description of the variables analysed is presented in Table 1.

Table 1

Description of variables analysed.
Variable	Description
Sphincter alterations	Incontinence, retention, urgency
Gait alterations	Limited, uncoordinated, difficult
Memory alterations	Retrograde, anterograde, mixed
Altered abdominal reflexes	Indifferent, abolished, diminished
Altered plantar reflexes	Extension, indifferent, abolished, diminished
Visual alterations	Blurred vision, double vision, phosphenes, scintillating scotomas, amaurosis fugax
Dysphasia	Altered speech, difficulty naming things and difficulty expressing oneself
Chronic generalized pain	Pain it at least 6 different points for at least 3 months

Figure 1. Prevalence of signs and symptoms (S&S) between the fibromyalgia/filum disease sample, and the filum disease sample. Where: blue indicates results with similar proportions between groups, and green indicates results without similar proportions between groups (p < 0.05). Dark blue and dark green correspond to the Fibromyalgia/Filum disease sample, and light blue and light green correspond to the Filum disease sample. Where: FD, filum disease; FM, fibromyalgia.

Radiological signs that presented similar proportions between samples included descent of the cerebellar tonsils (p = 010), syringomyelia (p = 0.08), and multiple discopathy (p = 0.96). However, scoliosis (p = 0.00) and low-lying conus medullaris (p = 0.00) showed different proportions between samples. The prevalence of these diagnoses is shown in Fig. 2.

Figure 2. Comparison of the additional diagnoses that present similar proportions between the Fibromyalgia/Filum disease sample and the Filum disease sample. (p < 0.05).

When assessing the clinical outcomes Fibromyalgia/Filum disease sample one month and one year after the surgery, a significant improvement (p < 0.05) was seen in most signs and symptoms, as shown in Table 2.

Table 2

Significant changes in the signs and symptoms after surgery.
Signs & Symptoms Pre-Op	8h Post-Op				1 Month Post-Op				1 Year Post-Op
Dysphagia					***	0,73	±	0,59		0,56	±	0,71
Paresthesias					***	0,89	±	0,33	*	0,57	±	0,53
Weak upper extremities					***	0,75	±	0,45		0,38	±	0,74
Nausea /vomiting					***	0,61	±	0,50	***	0,67	±	0,49
Headache					***	0,78	±	0,43	*	0,50	±	0,67
Cervical pain					***	0,63	±	0,50	**	0,50	±	0,52
Lower back pain					***	0,58	±	0,51	*	0,33	±	0,49
Dysphasia					***	0,82	±	0,40	***	0,88	±	0,35
Sonophobia					***	0,65	±	0,49	**	0,70	±	0,48
Photophobia					***	0,71	±	0,47	**	0,60	±	0,52
Blurred vision					***	0,73	±	0,47	*	0,57	±	0,53
Generalized pain					***	0,95	±	0,23	***	0,67	±	0,49
Dysphonia					**	0,80	±	0,45		0,40	±	0,55
Tinnitus					**	0,54	±	0,66	*	0,44	±	0,53
Instability					**	0,56	±	0,53		0,50	±	0,71
Visual alterations					*	0,69	±	0,63	**	0,70	±	0,48
Nervousness					*	0,60	±	0,52	*	0,44	±	0,53
Insomnia					*	0,39	±	0,50	*	0,42	±	0,51
Fatigue					*	0,54	±	0,52		0,29	±	0,49
Thoracic back pain					*	0,44	±	0,62	**	0,50	±	0,52
Memory alterations					*	0,55	±	0,52		0,25	±	0,46
Diplopia					*	0,71	±	0,49		0,33	±	0,58
Anxiety					*	0,58	±	0,51		0,40	±	0,55
Vertigo						0,46	±	0,69	*	0,44	±	0,53
Sphincter alterations						0,40	±	0,84	***	0,86	±	0,38
Thermal dysesthesia	***	0,70	±	0,47	***	0,83	±	0,39	***	0,70	±	0,48
Tactile dysesthesia	***	0,71	±	0,47	***	0,92	±	0,28	***	0,70	±	0,48
Deviated uvula					*	0,40	±	0,52		0,29	±	0,49
Positive Lasègue		0,17	±	0,41	**	0,64	±	0,50	**	0,75	±	0,46
Positive Romberg test		-0,29	±	0,49	**	0,60	±	0,63		0,30	±	0,48
Altered abdominal reflexes	**	0,83	±	0,41	**	0,46	±	0,52		0,50	±	0,55
Nystagmus	*	0,80	±	0,45		0,60	±	0,55	*	0,67	±	0,52
Altered plantar reflexes	*	0,63	±	0,52		0,10	±	0,57		0,29	±	0,49

Changes in signs and symptoms 8-hours, 1-month, 1-year post-operation, compared to pre-operation. Values are expressed as mean ± standard deviation. *** p < 0.001, ** p < .01, * p < .05.

Figures 3 and 4 present the improvement observed in signs and symptoms in the Filum disease/Neuro-cranio-vertebral syndrome sample, expressed as the percentage of cases that experienced amelioration of signs and symptoms in the post-operative visits (t-test for paired samples, p < 0.05).

Figure 3. Significant improvements in signs after SFT in the Filum disease/Neuro-cranio-vertebral syndrome sample of 25 patients. The results are expressed as the percentage of patients that experienced amelioration of signs 8 hours, 1 month and 1 year after the surgery (post-Op).

Figure 4. Significant improvements in symptoms after SFT in the Filum disease/Neuro-cranio-vertebral syndrome sample of 25 patients. The results are expressed as the percentage of patients that experienced amelioration of symptoms 1 month and 1 year after the surgery (post-Op).

Since the author began his research on idiopathic syringomyelia in the 1990s, which is presented in a doctoral thesis (Royo-Salvador MB. Contribution to the etiology of syringomyelia. [PhD thesis]. Barcelona, Spain: Autonomous University of Barcelona; 1992) much has been said and written about the etiology of Arnold-Chiari syndrome type I, idiopathic syringomyelia and scoliosis, without anyone being able to prove its causality. We believe that there is a single cause that explains the etiology of the three pathologies: the Filum disease. Filum disease is the result of the asynchronous development of the spine and the neuroaxis, beginning in the embryonic period and ending in puberty. This alteration of the normal function of the FT, which is likely congenital, causes a pathological traction of the entire neuroaxis. This leads to the clinical and radiological findings of ACSI, ISM (13) and IS (15), in addition to other pathological processes of the cranio-cervical junction such as platybasia, retroflexed odontoid, basilar impression (16), brainstem kinking and likely, disc diseases secondary to intradiscal mechanical disorders and normal spinal curvature.

The lengthening of the filum terminale due to the asynchronous growth between the spinal cord and the spine, or to histological alterations of the FT (fibrosis, increase in adipose tissue, hyalinization, degradation of collagen fibers, etc.) (17, 18), produces a mechanical traction on the filum terminale itself that translates into a traction force applied to the neuroaxis. This mechanical traction, both axial and lateral, manifests itself in various ways, including in ISM and ACSI. According to the results obtained in this study and those of other authors, we suggest that this mechanical traction can also result in FM (7, 8, 9, 19).

In 1953, Garceau (20) described the symptoms related to spinal cord traction and reported the cases of three patients with paraparesis, scoliosis, headache, and dysesthesia, who recovered after sectioning the FT. Other authors (21), a few years later, made the same observations and began to use the term tense filum. Roth (22) hypothesized that the lengthening of the spinal cord was responsible for scoliosis and Arnold-Chiari Syndrome Type I, and described a case of Filum disease with subsequent development of syringomyelia that improved after sectioning of the FT (22).

Some authors (23) consider that the spinal cord grows in response to stretching, a process that requires favorable conditions (blood perfusion, growth factors, etc.). A mismatch of these conditions (due to alteration of elastic properties, trauma, or neuronal degeneration because of inefficient elimination of free radicals generated by the mechanical effect of stretching), can lead to asynchronous bone growth, which then does not allow the nervous tissue to grow in response to stretching.

There are several theories behind the development of idiopathic scoliosis. Roth-Porter (23) hypothesizes that local neural dysfunction within the spinal cord is likely the cause of idiopathic scoliosis. The Roth-Porter hypothesis is also supported in the context of other mechanical hypotheses that can be extrapolated to different conditions of the spine and that consider various etiological mechanisms (24). Meanwhile, Lowe et al. (25) suggest that neurological dysfunction plays a key role in the genesis of idiopathic scoliosis.

When it comes to idiopathic syringomyelia, McLaurin et al. (26) and other researchers (27, 28, 29) have proposed that vascular restriction due to chronic hypoperfusion caused by spinal cord traction leads to tissue ischemia and to cavitation of the cervical and thoracic spinal cord. These regions of the spinal cord are supplied by the terminal branches of the anterior and posterior spinal arteries and are highly vulnerable to vascular reductions. A cat experimental model has recently replicated the slow and progressive traction exerted on the spinal cord, and the results from that study confirm the findings that have been stated thus far in this (30).

The histopathological study of Yamada et al. (31) on cervical cavitation showed an incomplete infarction, and a perfusion study revealed a decrease in blood flow in the cavitation. They also found a close correlation between the cervical vascular insufficiency and the tonsillar hernia that was the result of the hydrocephalus in patients with Arnold-Chiari Syndrome Type I.

Some researchers have hypothesized that there is a direct correlation between the cervicomedullary compression in the foramen magnum, due to the herniated cerebellar structure, and vascular insufficiency of the cervical spinal cord at a certain distance caudal from that level. Lichtenstein (32) and Foster et al. (33) suggest that the herniated cerebellar structures compress the neuroaxis and the vessels that cross the foramen magnum, and lead to a vascular insufficiency in the cervical cord. This hypothesis is based on their autopsy studies of the association of syringomyelia to Chiari malformation.

Syringomyelia may therefore be the lytic and cavitary expression of the elongation and restriction of the neuroaxis with altered central spinal cord perfusion, and scoliosis may be an attempt by the spinal cord to compensate for the traction force.

According to Depotter (34) scoliosis is present in addition to syringomyelia in 20% of cases, and in 70% of cases for Mau (35). Whereas Williams (36) and Royo-Salvador (7) suggest that they are both present in 75% of cases.

According to different authors (8, 9, 16, 19), Arnold-Chiari Syndrome Type I is the result of a descending traction of the neuroaxis in accordance, or not, with the currently most accepted theory of a small posterior fossa.

In our institution, we have developed a diagnostic and therapeutic protocol for the study of Filum disease based on clinical and radiological findings that allow for the association and description of Arnold-Chiari Syndrome Type I, syringomyelia and scoliosis in early stages (without established radiological lesions) and late stages (with established radiological lesions). It is interesting to note that this protocol allows the diagnosis of Filum disease —even without obvious radiological signs such as cerebellar tonsillar descent, syringomyelia or scoliosis, — and gives particular relevance to patients with FM that do not have evident radiological alterations.

Since the most widely accepted theory to explain the mechanism behind FM is central sensitization with an unknown origin, we think that the «tractional neurostress of the CNS» caused by Filum disease on the neuroaxis causes the neurophysiological changes necessary for the development of central sensitization described by several authors, including:

Altered cerebral function in patients with FM, as seen in fMRI imaging (36, 37)
Altered cerebral perfusion and metabolism in patients with FM, as seen in PET/SPECT scans (2, 5, 6)
Quantitative alterations in neurotransmitters of patients with FM (38)
Alterations in neuroendocrine and autonomous nervous (39, 40, 41, 42)
Structural changes in various cerebral areas (43)

To our knowledge, there is no data in the literature that refutes the hypothesis that fibromyalgia may be due to filum disease. On the contrary, there are several studies that support the strong correlation between FM and CNS neuropathophysiology in the context of Filum disease. There is plenty of evidence on neuroendocrine and autonomic deterioration in FM (39, 40, 41, 42) with symptoms very similar to those that occur in a high percentage of patients with Filum disease, which leads us to think that, at least in a limited subset of patients, FM can be considered secondary to Filum disease. The results obtained in the present study demonstrate the strong correlation between FM and Filum disease/Neuro-cranio-vertebral syndrome in relation to the multitude of common symptoms and neurological signs.

The clinical results obtained after sectioning the filum terminale in patients with FM are similar to those obtained by the group of Mantia et al. (12), where a significant improvement is observed after surgical intervention using the FS Method.

It is interesting to highlight the clinical neuropathology present in the sample of patients with Filum disease/Neuro-cranio-vertebral syndrome: altered tactile and thermal sensitivity, altered cutaneous reflexes, positive Romberg's sign, deviation of the uvula, and positive Lasègue and Mingazzini maneuver. These findings have not been mentioned in previous publications and they show the close relationship between FM and Filum disease. They are also objective clinical representations of central sensitization.

The main limitation of this retrospective study is the small size of the fibromyalgia/Filum disease sample (N = 25), particularly when compared to the Filum disease sample (N = 369). A larger sample size may have been more representative of the Filum disease sample, and it is possible that there would have been additional signs and symptoms that appeared in similar proportions between groups. It is also worth noting that the majority of the patients were from European descent, therefore, it is important to continue this research with diverse ethnic groups in order to have a deeper understanding of how fibromyalgia and Filum disease affect different ethnicities. Nevertheless, this study presents important results and prompts further work in this line of research.

What would the aetiopathogenic mechanism of central sensitization be, according to the filum disease theory?

The vector force exerted by the FD on the CNS (Fig. 5) results in a mechanical compromise that alters perfusion (44, 45, 46) and brain metabolism (39, 40, 41) in the narrowest intracranial areas, such as the tentorial notch and the foramen magnum. In the tentorial notch, the mesencephalon is compromised, and in the foramen magnum, the brainstem and the cerebellum are compromised, which could explain the phenomenon of central sensitization in the brain, and the changes observed by various authors (47, 48).

The pathological tractor effect of Filum disease acts on the spinal cord and causes a serious compromise in perfusion (47, 48), substantially altering the neurophysiology of nociception that results in the phenomenon of spinal sensitization (49, 50).

Figure 5. Schematic representation of the effects of filum disease and the Endoencephalic impact that follows.

At the top of the figure, the Endoencephalic Impact is highlighted (1), where the brain is displaced towards the posterior fossa, into the cerebellum and brainstem (2), affecting the foramen magnum, (A) displacing the cerebellum and increasing the supracerebellar arachnoid space (5) and lowering the cerebellar tonsils (A). The caudal force is also transmitted to the brain, generating intracerebral forces (3) towards the tentorial notch (B), mostly to the anterior-mid portions of the brain, and increasing the supracerebral arachnoid space (4), and to a lesser extent, the posterior cerebral area, due to the resistance of the tentorium (C).

The arrow to the left of the figure represents the vector force of the Filum disease, and the radiological lesions in Filum disease are described on the right side of the figure. The CNS is represented schematically in the middle of the diagram, with red line symbolizing central sensitization. The lilac arrow symbolizes the spino-thalamic pathway altered by the central sensitization mechanism.

The chronic traction of the nervous system, via the Filum terminale and the spinal cord, affects the brain, the foramen magnum, and the tentorial notch. The Endoencephalic Impact zones, as depicted in Fig. 5, coincide with the SPECT images of FM patients. They share similar vascular alterations and brain edema that is evident in magnetic resonance imaging of FM patients. In patients with Filum disease, these imaging results are most commonly seen in the coronal planes.

The results of the present study show the overlap of a multitude of signs and symptoms between FM and Filum disease, several of which are present in similar proportions between groups. This suggests a strong relationship between FM and Filum disease and suggests that a certain subgroup of FM patients have underlying Filum disease responsible for the development of central sensitization. There are even radiological signs that are strongly related between both diseases, namely, descent of the cerebellar tonsils, syringomyelia and multiple discopathy.

Surgical sectioning of the filum terminale results in a notable and significant improvement in signs and symptoms in a subset of FM patients diagnosed with Filum disease/Neuro-cranio-vertebral syndrome. We have ruled out that the placebo effect could have something to do with postoperative improvement since said placebo effect would not results in any changes in the clinical signs.

We can conclude that FM and Filum disease are, very likely, closely related to each other, that they share symptoms and clinical and radiological signs with high statistical significance, and that they both present significant clinical improvement after SFT, in accordance with the results published by Mantia et al. (12).

The results of this study highlight the need for a broader approach when assessing FM, including a detailed neurological exam with special emphasis on sensorial aspects and cutaneous reflexes, as well as neuroradiological imaging of the entire neuroaxis. This approach may facilitate the diagnosis of Filum disease/Neuro-cranio-vertebral syndrome in patients with FM and their subsequent treatment by SFT.

It is very likely that a subgroup of patients diagnosed with FM has Filum disease/Neuro-cranio-vertebral syndrome, and that this subset of patients would probably increase when applying the clinical and radiological protocol established in our institution for the diagnosis of Filum disease/Neuro-cranio-vertebral syndrome. The SFT via the FS Method is a safe and effective procedure that is minimally invasive, of short duration, and low risk with a low complication rate.

This study invites researchers to take on a new perspective towards the mechanisms behind central sensitization, and it opens the door for a prospective case-control analysis to further clarify the relationship between fibromyalgia and filum disease, as well as the results from sectioning of the filum terminale.

ACSI

arnold-chiari syndrome I

CNS

central nervous system

DCT

descent cerebellar tonsils

deviation of the spine

filum disease

fibromyalgia

filum terminale

hemivertebra

ICT

impaction of cerebellar tonsils

IDS

idiopathic deviation of the spine

IMC

intramedullary cyst

idiopathic scoliosis

ISM

idiopathic syringomyelia

LCM

low-lying conus medullaris

multiple discopathy

NCVS

neuro-cranio-vertebral syndrome

SCO

scoliosis

SFT

sectioning filum terminale

syringomyelia

SOC

suboccipital craniectomy

Ethics approval and consent to participate

We used our centre’s database of patient records retrospectively. Patient data were anonymised in accordance with the legislation existing when the study was initiated, following the necessary technical and organisational guarantees and measures, and without the requirement of an ethics committee. The need for informed consent and for approval of experimental protocols was deemed unnecessary according to the regulations established by Regulation (EU) 2016/679 Article 89.1 of the European Parliament and of the Council of 27 April 2016 (GDPR) and Organic Law 3/2018 of 5 December on the Protection of Personal Data and Guarantee of Digital Rights (LOPD). All methods were carried out in accordance with relevant guideline and regulations.

Consent for publication

Formal consent for the publication of participant data was not required, given that only anonymised data was used and followed the Regulation (EU) 2016/679 Article 89.1 of the European Parliament and of the Council of 27 April 2016 (GDPR) and Organic Law 3/2018 of 5 December on the Protection of Personal Data and Guarantee of Digital Rights (LOPD) of personal data protection. According to these regulations of personal data protection, this is sufficient, provided that a confidentiality commitment has been made and specific safety measures have been adopted.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author upon request.

Competing interests

The authors declare that they have no competing interests.

Funding

No funding was received for this research.

Author´s contributions

Study Design: MRS, JAA.
Data Collection: MRS, JAA.
Statistical Analysis: JAA, PV.
Data interpretation: JAA, PV.
Manuscript Preparation: MRS, JAA, MFR, IMV, PV.
Literature Search: MRS, JAA, IMV, PV.
All authors read and approved the final manuscript.

Acknowledgements

We thank Ms. Katharina Kühn for her help in translating and reviewing the manuscript, and Ms. Gioia Luè for her help in the management and organization of the institute´s R+D+I department. We would also like to thank Ms. Amelia Peirò for her help in the literature review for the study, and Mr. Javier Ibañéz de Aldecoa for his help with data analysis. Mr. Juan Manuel Jené Gaspar updated the FileMaker Pro database, and Ms. Mara Espino Hernández contributed administrative, social and financial management. And all the other staff at the Institut Chiari & Siringomielia & Escoliosis de Barcelona that have contributed to patient care and data collection, preparation, and analysis. We thank all our patients and caregivers, without whom this work would not have been possible.

Author Information

Miguel B. Royo-Salvadro: [email protected]

José Arteaga-Armas: [email protected]

Marco V. Fiallos-Rivera: [email protected]

Iolanda Miró-Vinaixa: [email protected]

Pamela Villavicencio: [email protected]

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No competing interests reported.

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Filum Disease Behind Fibromyalgia: A Preliminary Study

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