The Link Between Empty Sella Syndrome, Fibromyalgia, and Chronic Fatigue Syndrome: The Role of Increased Cerebrospinal Fluid Pressure.

The etiopathogenesis of fibromyalgia (FM) and chronic fatigue syndrome (CFS) is not yet elucidated. Hypothalamo-pituitary-adrenal (HPA) axis dysfunction is reflected in the hormonal disturbances found in FM and CFS. Some study groups have introduced a novel hypothesis that moderate or intermittent intracranial hypertension may be involved in the etiopathogenesis of FM and CFS. In these conditions, hormonal disturbances may be caused by the mechanical effect of increased cerebrospinal fluid pressure, which hampers blood flow in the pituitary gland. Severe intracranial pressure may compress the pituitary gland, resulting in primary empty sella (ES), potentially leading to pituitary hormone deficiencies. The aim of this narrative review was to explore whether similar hormonal changes and symptoms exist between primary ES and FM or CFS and to link them to cerebrospinal fluid pressure dysregulation. A thorough search of the PubMed and Web of Science databases and the reference lists of the included studies revealed that several clinical characteristics were more prevalent in primary ES, FM or CFS patients than in controls, including increased cerebrospinal fluid pressure, obesity, female sex, headaches and migraine, fatigue, visual disturbances (visual acuity and eye motility abnormalities), vestibulocochlear disturbances (vertigo and neurosensorial hearing loss), and bodily pain (radicular pain and small-fiber neuropathy). Furthermore, challenge tests of the pituitary gland showed similar abnormalities in all three conditions: blunted adrenocorticotropic hormone, cortisol, growth hormone, luteinizing hormone, and thyroid stimulating hormone responses and an increased prolactin response. The findings of this narrative review provide further support for the hypothesis that moderately or intermittently increased cerebrospinal fluid pressure is involved in the pathogenesis of FM and CFS and should stimulate further research into the etiopathogenesis of these conditions.

Large- and Small-Fiber Neuropathy in Patients with Tarlov Cysts.

PURPOSE: Tarlov cysts (TCs) are dilated nerve root sheaths originating from increased cerebrospinal pressure. Patients with TCs often complain of neuropathic pain and paresthesia. The aim of this study was to retrospectively review intraepidermal nerve fiber density (IENFD) and electrodiagnostic (EDX) data from TC patients. PATIENTS AND METHODS: Lower leg skin biopsy results and EDX data from the L2-S4 myotomes of patients with lumbar or sacral TCs ≥8 mm were retrieved from a database of a physical medicine clinic. Patients with compressive pathology, diabetes mellitus and chemotherapy were excluded. RESULTS: IENFD data from 17 patients and EDX data from 24 patients with TCs ≥8 mm were available. The mean age was 47 ± 10y, and 83% were women. In 82% of patients, the IENFD was below the 5th percentile by age and sex. EDX showed increased Hoffmann reflex latencies in 25%, increased anal reflex latencies in 95%, and a patchy distribution of neurogenic motor unit potentials in 100%. More than 50% of needle EMG abnormalities appeared in myotomes unrelated to the location of the TCs. CONCLUSION: Small- and/or large-fiber neuropathy was documented in a significant proportion of patients with TCs. The novel findings may add to the understanding of the mechanisms involved in symptomatic TCs. We propose that pathologically elevated cerebrospinal fluid pressure not only dilates some of the nerve root sheaths to form TCs but also potentially damages axons in nondilated nerve root sheaths and neurons in the dorsal root ganglia.

High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome.

OBJECTIVE: Pain in fibromyalgia (FM) and chronic fatigue syndrome (CFS) is assumed to originate from central sensitization. Perineural cysts or Tarlov cysts (TCs) are nerve root dilations resulting from pathologically increased cerebrospinal fluid pressure. These cysts initially affect sensory neurons and axons in dorsal root ganglia and produce sensory symptoms (pain and paresthesia). Symptomatic TC (STC) patients often complain about widespread pain and fatigue. Consequently, STC patients may initially be diagnosed with FM, CFS, or both. The objective of this study was to document the prevalence of TCs in patients diagnosed with FM or CFS. DESIGN: A retrospective study. SETTING: An outpatient clinic for musculoskeletal disorders. SUBJECTS: Patients diagnosed with FM according to the 1990 American College of Rheumatology criteria or with CFS according to the 1994 Centers for Disease Control criteria were selected. METHODS: Review of lumbar and sacral magnetic resonance imaging scans including TCs ≥5 mm in size. RESULTS: In total, 197 patients with FM, CFS, or both underwent magnetic resonance imaging. Ninety-one percent were women. The mean age was 48.1 (±11.9) years. TCs were observed in 39% of patients, with a mean size of 11.8 (±5.2) mm. In males, the prevalence was 12%, vs. 42% in females. CONCLUSIONS: In patients diagnosed with FM or CFS, the prevalence of TCs was three times higher than that in the general population. This observation supports the hypothesis that STCs, FM, and CFS may share the same pathophysiological mechanism, i.e., moderately increased cerebrospinal fluid pressure, causing irritation of neurons and axons in dorsal root ganglia.

Electrodiagnostic Abnormalities Associated with Fibromyalgia.

PURPOSE: Increasing evidence suggests that fibromyalgia most likely represents a neurological dysfunction. We previously hypothesized that at least some fibromyalgia cases may be caused by irritation of nerve root fibers and sensory neurons due to moderately increased cerebrospinal pressure. Because of the rostro-caudal hydrostatic pressure gradient, neurogenic abnormalities are expected to be most pronounced in sacral nerve roots. The purpose was to review electrodiagnostic tests of patients with fibromyalgia. METHODS: A retrospective review of electrodiagnostic test results, including the lumbar and sacral nerve root myotomes of patients diagnosed with fibromyalgia according to the 1990 criteria of the American College of Rheumatology was done. RESULTS: All 17 patients were female. Sural nerve responses could not be elicited in 12% and S1-Hoffmann reflex latencies were increased in 41%. In 12% of the patients, fibular motor nerve distal latency and conduction velocity were outside normal limits. Needle-EMG revealed neurogenic motor unit potentials in 0% of L2, 6% of L3, 29% of L4, 71% of L5, 47% of S1, 94% of S2, and 76% of S3-S4 myotomes. S3-S4 nerve-supplied anal reflexes were delayed in 94%. CONCLUSION: This is the first time that electrodiagnostic data of both lumbar and sacral nerve root myotomes in fibromyalgia patients are presented. All patients showed neurogenic abnormalities that were more pronounced in the sacral than in the lumbar myotomes with a rather patchy distribution pattern. We propose that, in addition to skin punch biopsies to assess small fiber neuropathy, assessment of the anal reflex may be a useful part of the diagnostic pathway in patients with fibromyalgia.

Hydrocephalus associated with multiple Tarlov cysts.

Tarlov cysts (TCs) consist of dilated nerve root sheaths filled with cerebrospinal fluid (CSF) and are most frequently found in the sacrum. It is estimated that 25% of detected TCs cause chronic pain and intestinal and urogenital symptoms due to compression of the sacral nerve root fibers inside the TC. Unfortunately, symptomatic TCs are frequently overlooked. It is assumed that TCs result from pathologically increased hydrostatic pressure (HP) in the dural sac that forces CSF into the nerve root sheaths. We hypothesize that in patients with TCs, increased spinal hydrostatic pressure is always associated with increased intracranial pressure. This hypothesis of increased cerebrospinal pressure might explain why patients with sacral TCs frequently report distant symptoms, such as headaches and pain in the neck and arms. In this paper, we describe a case report that provides evidence for this hypothesis. A 30-year-old man presented for the first time in our clinic complaining of lower back, leg, thoracic, neck, and arm pain; headaches; and bladder, bowel, and sphincter symptoms. He was born prematurely and suffered cerebral intraventricular bleeding followed by progressive hydrocephalus. Progression was stabilized with acetazolamide and lumbar punctures. At 19 years of age, his head circumference had further increased and he reported back pain and headaches. Fundoscopy showed no papilledema, and lumbar puncture for CSF evacuation improved the headaches and back pain. The former medical team chose not to insert a ventriculo-external shunt. Brain magnetic resonance imaging (MRI) showed significant dilation of all the ventricles. No CSF flow obstruction between the ventricles was observed. Surprisingly, MRI of the lumbar and sacral spine showed multiple large TCs. This case report indicates that hydrocephalus with a patent aqueduct may be associated with TCs because the increased intracranial pressure is transferred to the spinal canal. While increased intracranial pressure causes dilation of the ventricles, the associated increased spinal pressure may cause dilation of multiple spinal nerve root sheaths to form TCs. Furthermore, while the increased volume of the ventricles gradually compresses the neurons and axons of the brain against the bony skull, simultaneously, the increased pressure inside the nerve sheaths may also gradually compress the neurons and axons located inside the dorsal root ganglia and spinal nerves, resulting in neuropathic pain, sensory abnormalities, and neurogenic bladder and bowel symptoms. Hydrocephalus patients reporting neuropathic pain should be screened for the presence of TCs.

Symptomatic Tarlov cysts are often overlooked: ten reasons why-a narrative review.

PURPOSE: Tarlov cysts (TCs) are dilations of nerve roots arising from pathologically increased hydrostatic pressure (HP) in the spinal canal. There is much controversy regarding whether these cysts are a rare source of pain or often produce symptoms. The aim of this review was to identify the reasons that symptomatic TCs (STCs) are easily overlooked. METHODS: The literature was searched for data regarding pathogenesis and symptomatology. RESULTS: TCs may be overlooked for the following reasons: (1) STCs are considered clinically irrelevant findings; (2) it is assumed that it is clinically difficult to ascertain that TCs are the cause of pain; (3) MRI or electromyography studies only focus on the L1 to S1 nerves; (4) TCs are usually not reported by radiologists; (5) degenerative alterations of the lumbosacral spine are almost always identified as the cause of a patient's pain; (6) it is not generally known that small TCs can be symptomatic; (7) examinations and treatments usually focus on the cysts as an underlying mechanism; however, essentially, increased HP is the main underlying mechanism for producing symptoms. Consequently, STCs may relapse after surgery; (8) bladder, bowel and sphincter dysfunction are not inquired about during history taking. (9) Unexplained pain is often attributed to depression, whereas depression is more likely the consequence of debilitating neuropathic pain. (10) The recognition of STCs is subject to gender bias, confirmation bias and cognitive dissonance and unconscious bias in publishing. CONCLUSION: There are several reasons STCs are underdiagnosed, mostly due to persistent misconceptions and biases. These slides can be retrieved under Electronic Supplementary Material.

The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology.

PURPOSE: Idiopathic intracranial hypertension (IICH) is a condition characterized by raised intracranial pressure (ICP), and its diagnosis is established when the opening pressure measured during a lumbar puncture is elevated >20 cm H2O in nonobese patients or >25 cm H2O in obese patients. Papilledema is caused by forced filling of the optic nerve sheath with cerebrospinal fluid (CSF). Other common but underappreciated symptoms of IICH are neck pain, back pain, and radicular pain in the arms and legs resulting from associated increased spinal pressure and forced filling of the spinal nerves with CSF. Widespread pain and also several other characteristics of IICH share notable similarities with characteristics of fibromyalgia (FM) and chronic fatigue syndrome (CFS), two overlapping chronic pain conditions. The aim of this review was to compare literature data regarding the characteristics of IICH, FM, and CFS and to link the shared data to an apparent underlying physiopathology, that is, increased ICP. METHODS: Data in the literature regarding these three conditions were compared and linked to the hypothesis of the shared underlying physiopathology of increased cerebrospinal pressure. RESULTS: The shared characteristics of IICH, FM, and CFS that can be caused by increased ICP include headaches, fatigue, cognitive impairment, loss of gray matter, involvement of cranial nerves, and overload of the lymphatic olfactory pathway. Increased pressure in the spinal canal and in peripheral nerve root sheaths causes widespread pain, weakness in the arms and legs, walking difficulties (ataxia), and bladder, bowel, and sphincter symptoms. Additionally, IICH, FM, and CFS are frequently associated with sympathetic overactivity symptoms and obesity. These conditions share a strong female predominance and are frequently associated with Ehlers-Danlos syndrome. CONCLUSION: IICH, FM, and CFS share a large variety of symptoms that might all be explained by the same pathophysiology of increased cerebrospinal pressure.

Postarachnoiditis Anterior Spinal Arachnoid Cyst Formation with Compressive Myelopathy: Report of 2 Cases.

BACKGROUND: Spinal cystic arachnoiditis is a rare complication of a subarachnoid haemorrhage or infectious meningitis. The inflammatory process leads to fibrosis, adhesions, and in severe cases cyst formation. Large arachnoid cysts are an uncommon cause of compressive myelopathy. The majority are located posterior of the spinal cord at the thoracic level. Anterior cyst formation is exceptional, especially at the cervical region. CASE DESCRIPTION: We present 2 cases of progressive myelopathy secondary to anterior arachnoid cyst formation. In a 54-year-old female a large anterior symptomatic thoracic cyst arose 4 years after rupture of a posterior inferior cerebellar artery aneurysm. The other 59-year-old-patient, however, developed an anterior cervical cyst only weeks after a varicella meningoencephalitis. Both female patients were treated with a decompressive laminectomy and wide fenestration of the cysts. Partial recovery was obtained in 1 patient, but there was no improvement in the other case. CONCLUSIONS: Spinal cystic arachnoiditis with anterior cyst formation is an extremely rare complication of subarachnoid haemorrhage and infectious meningitis but can cause severe neurologic deficits. Clinicians should be aware of this rare complication. Due to the risk of irreversible spinal cord injury, rapid surgical intervention is recommended in most cases.

Can patients with symptomatic Tarlov cysts be differentiated from patients with specific low back pain based on comprehensive history taking?

BACKGROUND: Tarlov cysts (TCs) are expanded nerve root sheaths that occur near the dorsal root ganglion and result from increased intraspinal hydrostatic pressure. TCs most frequently affect the lumbosacral plexus and therefore may cause specific symptoms such as perineal pain and neurogenic bladder, bowel, and sphincter problems. It has been estimated that 1% of the population has symptomatic Tarlov cysts (STCs). However, STCs appear to be underdiagnosed, with the pain reported by patients commonly attributed to degenerative alterations seen on MRI. The aim of the present study is to investigate the utility of a comprehensive questionnaire for use by physicians in establishing the diagnosis of STCs. METHODS: We compared questionnaire responses regarding patient history between 33 patients diagnosed with symptomatic TCs and 42 patients with chronic low back pain and sciatica due to disc problems or degenerative or inflammatory disorders. The diagnosis of STCs was confirmed using nerve conduction studies (NCS) and electromyography (EMG) of the sacral myotomes by an expert neurophysiologist. RESULTS: The questionnaire responses revealed specific differences in perineal symptoms (perineal pain, dyspareunia, coccygodynia), bowel symptoms (constipation, diarrhea), bladder symptoms (hesitation, retention, frequency), and anal sphincter problems (anal pain, mild fecal incontinence). Additionally, sitting, walking, and straining aggravated pain more frequently in STC patients, and STC patients were more often forced to stop working and/or reduce their social activities. CONCLUSIONS: Including the above-listed items in the patient history might facilitate differentiation of low back pain and sciatica due to STCs from that due to disc problems or degenerative or inflammatory disorders.