My journey with peripheral polyneuropathy has probably lasted my lifetime. It made itself known along the way but by 2009 its whisper was clearly audible, by 2011 it was shouting, by 2012 it was screaming at me. But what on earth had caused this autonomic then sensory, then by 2013 even the start of motor neuropathies?
I was born to an alcoholic who had attempted (failed) abortion twice with Quinine so peripheral nerve damage right from the start may well have been probable. By six months old I had recurrent infections (later diagnosed as primary immune deficiencies) and a number of viruses that could have caused it. I may have inherited salt wasting from my father and certainly did inherit a collagen disorder from my mother. Did I have symptoms of autonomic, sensory or motor neuropathies in early childhood? Autonomic, certainly, sensory, on and off, motor, maybe, episodically at different times throughout my life.
The closest we came to understanding why my polyneuropathy got to the level its now at was the theory that my collagen disorder – Ehlers Danlos Syndrome – had played a part; that collagen protects myelin which protects peripheral nerves and mine is degenerating. Another specialist suggested my autonomic neuropathy had developed as a result of chemo. But being immune deficient all my life, I wondered if this also played a part, particularly as I’d had Chicken Pox, EBV and Herpes Simplex 1 (cold sore virus), all of which have been linked to peripheral neuropathies. And what of salt craving and my dramatic improvements when on high sodium intake? I knew chemo had tipped the balance and that Tomoxifen was implicated. But how to make sense of the puzzle, the fruit salad?
I could have accepted the word ‘idiopathic’ but maybe that’s just a word people have when they cannot find the ONE cause. But what if that’s because there actually were multiple, cumulative causes? This is what I came up with (together with cited associated medical studies):
1) SALT WASTING
I was a heavy salt craver all my life, as was my (rather autism spectrum) father who would coat his food until it was white and said if he didn’t keep up with salt he got headaches. I craved high salt foods, added salt and from mid childhood to my early teens drank saline on a daily basis. When, during chemo in 2011, I was told I had autonomic dysfunction I didn’t think to supplement salt because the chemo had already caused me to have a permanent taste in my mouth of salt. Following chemo and diagnosis of Orthostatic Hypotension, Arrythmia and Mixed Apnea, I read up about sodium and autonomic dysfunction and began to take 5 grams a day of sodium (around 10 grams of salt) which I took in addition to magnesium, calcium and citrulline supplementation. My autonomic dysfunction improved significantly though the hypoventilation continued. My sleep specialist suspected I had salt wasting and ordered electrolyte levels tested. On 5 grams of sodium a day my sodium levels (and other the electrolytes I was already supplementing) were ‘normal’. Before this, I have no idea.
I looked up salt wasting and found that whilst Barter’s Syndrome is almost always diagnosed in infancy, a related but usually milder condition, Gitelman’s Syndrome, can go undiagnosed into adulthood until a health crises exposes it. To test for Gitelman’s I’d have to come off sodium for 2 weeks. I dropped it to 2.5 grams a day and had severe polyuria. Gitelman’s is one cause of hypoventilation syndrome in children. My hypoventilation was probably happening since age 2-3, daytime hypopnea/bradypnea as long as I can recall, episodes of being ‘blue’ from age 2-3. Hypoventilation episodes can contribute to developmental disabilities and sensory perceptual disorders – I was diagnosed with autism at the age of 2.
Frank A. Zelko; Michael N. Nelson; Sue E. Leurgans; Elizabeth M. Berry-Kravis; Debra E. Weese-Mayer (Profiled Authors: Frank A Zelko; Debra E Weese-Mayer)
Pediatric Pulmonology. 2010;45(1):92-98. Scopus
Objective: Examine indices of neurocognitive functioning in children with PHOX2B mutation-confirmed neonatal onset congenital central hypoventilation syndrome (CCHS) and relate them to indices of PHOX2B genotype, demographics, and disease severity. Methods: Subjects were 20 patients with PHOX2B mutation-confirmed CCHS diagnosed as neonates who had undergone neurocognitive assessment in the course of clinical care at the Rush Children’s Hospital CCHS Center between 1990 and 2006. Neurocognitive variables of interest included Full Scale IQ (FSIQ) and Wechsler-derived marker indices (subtests) of verbal comprehension (Vocabulary), visuoperceptual reasoning (Block Design), working memory (Digit Span), and clerical/processing speed (Coding). Results: Single sample t-tests revealed participants’ general intelligence index (FSIQ; mean 84.9, SD 23.6) to be lower than the general population, though the range of FSIQ observed was broad. Visuoperceptual reasoning and clerical/visuographic speed marker indices were similarly depressed. These deficits were related to special education participation but not to PHOX2B genotype status or other demographic and clinical risk factors. Conclusions: PHOX2B mutation-confirmed CCHS confers risk for adverse neurocognitive outcome, though the range of functioning observed raises questions about factors that may contribute to neurocognitive variability. Visuoperceptual reasoning and clerical/visuographic speed appear particularly vulnerable. PHOX2B genotype and disease severity indicators were unrelated to neurocognitive indices, possibly due to our modest sample. Future research should employ comprehensive neurocognitive assessment emphasizing visuoperceptual ability, mental speed, attention, and information processing efficiency. Increased recognition and expedited diagnosis with PHOX2B testing should allow larger studies of the relationship between neurocognitive functioning, PHOX2B genotype/mutation, and disease severity and management. © 2009 Wiley-Liss, Inc.
2) EPISODIC HYPOXIA
I was commonly blueish as a young child, always pale to the point I was called ‘Baby Legs’ and ‘Milk Bottle’. I was dizzy a lot of the time, it was normal for me to feel a little ‘out of it’ so I didn’t question it. I drowned twice at age 3, rescued from the bottom of the pool as I’d made no effort to breathe. Later I could spend more time underwater than any child I knew and easily swam the length of the Olympic pool on the bottom. So its fair to say that hypoventilation was probably my ‘norm’. When I was 2-3 years old I also experienced a year of being choked and suffocated by an abuser (I took to then sleeping under the bed, which ‘solved’ some of this). I’m sure this did my nerve health no favors whatsoever. Nevertheless, my brain MRI looks fine. So was their no damage? Or was the only damage to the peripheral nerves?
Peripheral Neuropathy in Sleep Apnea
A Tissue Marker of the Severity of Nocturnal Desaturation
PIERRE MAYER, MAURICE DEMATTEIS, JEAN LOUIS PÉPIN, BERNARD WUYAM, DAN VEALE, ANNICK VILA, and PATRICK LÉVY
Changes occur in peripheral nerves subjected to hypoxemia resulting from a low blood O2 concentration such as in chronic obstructive pulmonary disease (COPD), or to damage to the vasa nervorum causing ischemia, such as in diabetes. A modified tolerance of peripheral nerves to transient, experimentally induced limb ischemia has been reported in hypoxic COPD and diabetic patients (12, 13). This tolerance is characterized by abnormal persisting nerve conduction during ischemia. This resistance to ischemic conduction failure (RICF) seems to be the earliest abnormality of peripheral nerve function observed in diabetic patients who go on to develop an obvious neuropathy (14). The tolerance to ischemia may be an adaptative mechanism, since some electrophysiologic abnormalities have been reversed in hypoxic patients by improvement of oxygenation (12), and in diabetic rats by supplemental oxygen inhalation (15).
Chronic hypoxia is a well known cause of peripheral neuropathy (16-18). However, to our knowledge, no study has been done of peripheral neuropathy related to intermittent hypoxia except for the pharyngeal thermal hypoesthesia described in patients with OSA, which may be related to a pharyngeal neuropathy (19). The aim of the present study was therefore to assess peripheral nerve function with an ischemia test in OSA patients without a recognized cause of neuropathy. This type of dysfunction may represent an early and quantifiable tissue marker of the consequences of nocturnal hypoxemia.
Read More: http://www.atsjournals.org/doi/full/10.1164/ajrccm.159.1.9709051#.UqvKoI0YMck
3) EHLERS-DANLOS SYNDROME (EDS).
I was hypermobile since at least age 2-3, was turned into a ‘human pretzel’ by my mother for the entertainment of others and could easily put my feet to my head and rock, put my feet behind my head like a ‘frisbee’, do the splits and turn from one legs to the other. My history of progressive connective tissue degeneration is the usual for someone with EDS starting with diagnosis of juvenile arthritis in late childhood. It was only when I was diagnosed with Ehlers-Danlos Syndrome in 2013 that I learned I have 4 relatives on my mother’s side who have ruptured before the age of 40 – two with uterus rupture, one with spleen rupture, one with brain aneurysms. As such I’m thought to likely have EDS type IV. There is recent literature connecting EDS to some forms of autism.
Enrique Galan, MD, Boris G. Kousseff, MD
Received 18 July 1994; accepted 28 December 1994.
Two unrelated male patients with clinical manifestations of Ehlers-Danlos syndrome type III and peripheral neuropathy are presented. At age 13 years, one developed bilateral brachial plexus palsy unrelated to trauma and 2 years later, a right lumbosacral plexopathy. The other presented at age 3 years with a left brachial plexopathy after sustaining a fracture of the lateral condyle of the right humerus. In both patients, nerve conduction velocities demonstrated conduction block across the brachial plexus and recovery was incomplete, indicating that peripheral neuropathy is a serious complication of Ehlers-Danlos syndrome. Its prompt diagnosis facilitates the care of patients with this syndrome. Increased ligament laxity/stretchability and mechanical trauma may play an important role in the pathogenesis of the neuropathy.
Neurology. 1976 Jun;26(6 PT 1):596-7.
4) IgG SUBCLASS DEFICIENCIES
I had recurrent infections from 6 months of age with my first 26 years regularly on antibiotics. I first became personally aware of my immune deficiencies when I was 17 and the nurse kept taking more and more blood samples because they couldn’t find any white cells. By the age of 38 I had my first normal white cell count but was then diagnosed with severe IgA deficiency (only trace). This improved but by my 40s remained mildly deficient. In 2009 I was found to be IgG2 deficient, and by 2011 also IgG4 deficient. The latter resolved but I remained IgG2 deficient.
Neurology. 1999 Jun 10;52(9):1902-5.
Recurrent multifocal demyelinating neuropathy with febrile illness and IgG subset deficiency.
Likosky DJ, Kraus EE, Yuen EC.
Department of Neurology, University of Washington, Seattle 98195, USA.
We describe a unique syndrome of recurrent multifocal demyelinating motor greater than sensory deficits in cranial and peripheral nerve distributions with rapid, spontaneous improvement. Three patients presented with episodes over a period of 7 to 24 years, largely accompanied by febrile illness. Variably decreased IgG1 and IgG3 subclass levels were found. We postulate an immune-mediated process based upon the clinical presentation and presence of decreased IgG subclass levels.
10371544 [PubMed - indexed for MEDLINE]
IgG monoclonal paraproteinaemia and peripheral neuropathy.
A F Bleasel, S H Hawke, J D Pollard, and J G McLeod
Author information ► Copyright and License information ►
This article has been cited by other articles in PMC.
Five patients with peripheral neuropathy and benign IgG monoclonal paraproteinemia are reported, all of whom had a sensorimotor neuropathy with a remitting and relapsing course. The serum paraprotein level did not correlate with the patient’s clinical status. Electrophsyiological studies showed marked slowing of conduction velocity and conduction block in four of the patients and mild slowing in the other. Sural nerve biopsies demonstrated a demyelinating neuropathy with inflammatory cell infiltrates in each of the five patients. Three of the patients had evidence of myelin/Schwann cell reactivity on immunofluorescence studies and in all nerves dense expression of major histocompatability complex class I and II molecules was evident within the endoneurium, on invading mononuclear cells, endothelial cells and Schwann cells. All the patients responded to treatment, plasmapheresis being particularly effective. Four patients have achieved prolonged remissions after all treatment had ceased. These five cases of peripheral neuropathy and IgG paraproteinaemia were identical in their clinical, electrophysiological and pathological features to patients with chronic inflammatory demyelinating polyneuropathy.
J Neurol Neurosurg Psychiatry. 1993 January; 56(1): 52–57.
I had Tourette’s since age 2 (part of my dx with autism at age 2 referred to my to Tourette’s tics) as part of constant Strep infections associated with IgG2 deficiency in a wider context of primary immune deficiencies.
Sommer C, Schröder JM.
Source: Institut für Neuropathologie, Rheinisch-Westfälischen Technischen Hochschule Aachen, Germany.
A 22-year-old man suffered from a complete flaccid tetraparesis and an immune complex-mediated rapid progressive glomerulonephritis after group A streptococcal infection. Serum creatine kinase was excessively elevated and myoglobinuria occurred. Nerve conduction studies revealed evidence of axonal neuropathy. Recovery was satisfactory within 18 months. Sural nerve and peroneus muscle biopsies were performed in the 4th and 14th week of the disease. Light microscopy of the sural nerve showed an incipient axonal type of neuropathy in the first biopsy. Ultrastructurally, Wallerian degeneration and endoneurial inflammatory cells were present. In the muscle biopsy, few atrophic fibers and altered blood vessels without further anomalies were found. In the second sural nerve biopsy, macrophages were numerous, some of which were immunoreactive for HLA-DR, and only a few myelinated and some unmyelinated nerve fibers remained. Muscle fibers in the second biopsy showed high-grade atrophy and myofibrillar abnormalities. Immunohistochemistry revealed diffuse endoneurial immunoglobulin deposition in the first sample, while in the later biopsy specimen, deposits of IgG, and kappa and lambda light chains were visible in circumscribed endoneurial areas. Immune-mediated neuropathy and myopathy are not well-known complications of streptococcal disease. This is, to our knowledge, the first detailed report on morphological findings in muscle and nerve in such a disorder.
PMID: 1318816 [PubMed - indexed for MEDLINE]
6) HERPES SIMPLEX
I had Herpes Simplex 1 (the cold sore virus) since primary school, still get flare ups with cold sores now. I also had Chicken pox (Varicella Zoster) at age 16 and Epstein Barr Virus (EBV) in my 20s, all of them herpes viruses.
Krohel GB, Richardson JR, Farrell DF.
Atypical facial pain and permanent sensory loss in the second and third divisions of the trigeminal nerve developed in a patient who had had multiple attacks of herpes simplex neuralgia over a period of 8 years. Intravenous cytosine arabinoside failed to prevent a recurrence of the vasicular eruption, but carbamazepine produced symtomatic pain relief. This case demonstrates that herpes simplex can closely mimic herpes zoster as a cause of postherpetic neuralgia and suggests a possible etiology of atypical facial pain and/or trigeminal sensory neuropaty in some patients.
PMID: 945505 [PubMed - indexed for MEDLINE] Brain. 2000 Oct;123 ( Pt 10):2171-8.
Autonomic (especially hypoventilation) and sensory-motor neuropathies escalated in 2010 following 7 mths of Haemophilus (am IgG2 deficient so was on Doxycycline ever since),
Mori M, Kuwabara S, Miyake M, Noda M, Kuroki H, Kanno H, Ogawara K, Hattori T.
Source: Department of Neurology, Chiba University School of Medicine, Chiba, Japan. email@example.com
It has been reported recently that Haemophilus influenzae can elicit an axonal form of Guillain-Barré syndrome. To investigate the incidence and features of H. influenzae-related Guillain-Barré syndrome, anti-H. influenzae antibody titres were measured by enzyme-linked immunosorbent assay (ELISA) in 46 consecutive Japanese patients with Guillain-Barré syndrome, 49 normal controls, 24 patients with multiple sclerosis and 27 patients with amyotrophic lateral sclerosis (ALS). Whole bacteria of non-encapsulated (non-typable) H. influenzae isolated from one of the Guillain-Barré syndrome patients was the antigen used. Elevated anti-H. influenzae antibodies for two or three classes of IgG, IgM and IgA were found in six (13%) Guillain-Barré syndrome patients, but not in the normal controls and patients with multiple sclerosis or ALS. The incidence was significantly higher in patients with Guillain-Barré syndrome than in the normal controls (P = 0.01) and patients with multiple sclerosis or ALS (P = 0.009). Western blot analysis confirmed that the H. influenzae-positive patients’ IgG recognized the lipopolysaccharides of H. influenzae. Guillain-Barré syndrome patients with anti-H. influenzae antibodies showed relatively uniform clinical and laboratory features: prodromal respiratory infection, less frequent cranial and sensory nerve involvement, pure motor axonal degeneration on electrophysiology, and positivity for IgG anti-GM1 antibodies. Although the features were similar to those in Guillain-Barré syndrome patients infected by Campylobacter jejuni, the recoveries seemed to be better in patients with H. influenzae-related Guillain-Barré syndrome. It is concluded that a form of Guillain-Barré syndrome occurs after respiratory infection by H. influenzae in the Japanese population. A particular strain of non-typable H. influenzae has a ganglioside GM1-like structure and elicits axonal Guillain-Barré syndrome similar to C. jejuni-related Guillain-Barré syndrome.
PMID: 11004133 [PubMed - indexed for MEDLINE] Neurology. 1996 Jan;46(1):108-11.
8) COELIAC DISEASE
I was wheat/rye free in 1990, then returned to wheat on and off until 2001, then was dx’d as gluten intolerant due to undigested gluten related proteins in my urine, then in 2011 had an IgA coeliac test which was negative and a bowel biopsy that was negative for coeliac and an IgE blood test that showed allergy to wheat. I went wheat free in 2010. 30% of relatives on my paternal grandmother’s side have coeliac or gluten intolerance.
I’m IgA deficient. The test for coeliac is an IgA blood test and those with IgA deficiency as standard have false negatives on this test. The bowel biopsy should be done when the person is still having gluten. When I had the biopsy I had been off gluten for almost ten years. They found no damage. Of course, having been off gluten for 10 years why should they. But people believe what they want to believe, what’s convenient to believe, what’s more delicious to believe… I went back onto gluten. IgA deficiency is 10-15 times higher incidence in people with coeliac even though only 3-5% of people with coeliac have IgA deficiency. Like diabetes, untreated coeliac is one of the most common causes of progressive peripheral neuropathy.
Curr Treat Options Neurol. 2005 Jan;7(1):43-48.
Peripheral Neuropathy and Celiac Disease. Chin RL, Latov N.
Peripheral neuropathy (PN) is one of the most frequently reported neurologic manifestations associated with celiac disease (CD), a multigenetic, T-cell-mediated autoimmune disorder that results from a loss of tolerance to gluten. Sensory axonal and small fiber sensory polyneuropathies are the most frequently reported PN subtypes. Multifocal motor or sensorimotor neuropathies and a more fulminant neuropathy, associated with ataxia and other neurologic manifestations, also have been reported. The effect of a gluten-free diet on CD-associated PN has not been studied systematically or prospectively; nevertheless, a gluten-free diet currently is the cornerstone of therapy. Although idiopathic ataxia associated with anti-gliadin antibodies and other neurologic complications have been reported to respond to this diet; there is data that indicate that neurologic manifestations may develop or persist, independent of gluten exposure. There is evidence to suggest that inflammatory processes may be involved. Immunomodulatory agents (such as intravenous immunoglobulin or infliximab), described to be beneficial in the treatment of refractory CD or CD-associated ataxia, may have a role in the management of CD-associated PN.
15610706 [PubMed - as supplied by publisher]
The autonomic neuropathy was out of control during chemo with Docetaxel in 2011 and post chemo
New PZ, Jackson CE, Rinaldi D, Burris H, Barohn RJ.
Source: Department of Medicine/Neurology, University of Texas Health Science Center, San Antonio 78284-7883, USA. Comment in Docetaxel neuropathy. [Neurology. 1996]
Docetaxel (Taxotere), a semisynthetic analogue of the antitumor agent paclitaxel, inhibits tubulin depolymerization. Paclitaxel produces a peripheral neuropathy. This study delineates clinically and electrophysiologically the characteristics of a peripheral neuropathy due to docetaxel. In 186 patients receiving docetaxel in phase I and phase II protocols, we performed serial neurologic exams. As patients became symptomatic, quantitative sensory testing and nerve conduction studies were done. Twenty-one patients developed mild to moderate sensory neuropathy on taxotere at a wide range of cumulative doses (50 to 750 mg/m2) and dose levels (10 to 115 mg/m2). Ten of these patients also developed weakness of varying degree in proximal and distal extremities. Nine of the 21 patients had received neurotoxic chemotherapy before; 16 were treated with docetaxel at a dose level of 100 to 115 mg/m2. In summary, docetaxel produced a sensorimotor peripheral neuropathy in 11% of our patient population.
PMID: 8559355 [PubMed - indexed for MEDLINE]
10) DEGENERATIVE LUMBAR SPINAL STENOSIS
Spine degeneration is usual with Ehlers Danlos Syndrome and I’d had sciatica since late childhood and regularly had challenges with my joints, neck, back. But I never envisioned that before the age of 50 I’d be diagnosed with degenerative spinal stenosis. Very shortly after chemo I had a severe bout of sciatica.
I’m so used to it I’d come off painkillers by my late teens and so I ignored it as usual. It was the worst episode I have ever had. The surging pains began stabbing from both sides, becoming almost circular around my torso. I was frozen with pain, couldn’t even scream.
Next I had four days of paralysis of my lumbar and thigh muscles. I could barely walk, couldn’t stand up from the toilet or sit up in bed, couldn’t get myself up off the floor or straighten after reaching down into a cupboard. An MRI revealed degenerative lumbar spinal stenosis.
My spinal cord was being squeezed by a thickened ligament (most likely in response to years of inflammation and scarring), I had several ruptured discs, and arthritis related damage limiting nerve exits and leaving nerves in contact and at risk of being damaged. I was told the four days of paralysis was due to a ‘sciatic storm’ triggering a neurological shutdown of movement to the lumbar and thigh muscles because I was ignoring the pain, a process called ‘pain inhibition’. I was told I’d need back surgery within a year.
I saw a physiotherapist, worked on all I could to regain abilities, took advice and made my desk a standing desk, bought ring cushions for the car, my seat at the dining table, a portable one for if out at the cinema, theatre, for dinner, and accepted the medical advice that I’d never jump from anything, would get rid of my trampoline and would never do another long haul flight unless it was laying down or sit for longer than 2 hours.
It did get harder and harder to walk after sitting but the ability would return after 30 seconds of walking. Two years post diagnosis I began to get buzzing surging up and down my legs, sudden loss of sensation to one or both legs, falling up steps, and sudden return of sensation with associated severe heaviness. Whilst I accepted that lumbar spinal stenosis could cause me peripheral neuropathy effecting the lower limbs, perhaps even the bladder and bowel, it did not account for the other forms of neuropathy I was having (MRI showed only the lumbar spine was significantly damaged). So even if it was part of the whole picture, it was not the whole.
Lumbar spinal stenosis is well defined in patho-anatomical terms but its clinical features are heterogeneous. We carried out a comprehensive retrospective review of the clinical features, radiological changes and outcome of 75 patients with radiologically diagnosed lumbar spinal stenosis in order to define its clinical spectrum. The presenting complaints were of weakness, numbness/tingling, radicular pain and neurogenic claudication in almost equal proportions. The commonest symptom was numbness or tingling of the legs. Neurogenic claudication eventually occurred in only 61%. Ninety-three per cent showed abnormalities on neurological examination, but these were generally mild with reduced ankle jerks being commonest. Imaging of the lumbar spine showed that moderate to severe central spinal stenosis correlated with complaints of weakness and abnormal motor power on clinical examination. Patients were reviewed at a mean of 4 years after diagnosis and 65% had undergone surgical decompression; this was not a prospective comparison of different treatment modalities. Overall, a third of patients felt that their symptoms had improved while a quarter felt that they had worsened. More than half had satisfactory neurological function at the time of review. Thirty-nine per cent of those treated surgically, and 25% of those managed conservatively, reported improved symptoms. A poorer functional status at review correlated with complaints of motor weakness and associated comorbid disease. Degenerative lumbar stenosis is a clinically heterogeneous neurological disorder of the lower limbs in the elderly with variable longer-term outcome. A high index of suspicion is required and neuroimaging should be obtained to confirm the diagnosis.
2004 S. Karger AG, Basel. PMID: 15583458 [PubMed - indexed for MEDLINE]
Within weeks of starting Tomoxifen the autonomic neuropathy expanded into sensory neuropathies through 2012 and the start of motor neuropathies began in 2013.
Collagen protects myelin which protects peripheral nerves and collagen is an essential part of all connective tissue. The health of connective tissue is essential to both messages coming from the peripheral nerves to muscles, joints, ligaments, tendons etc, but also messages from tissues to the peripheral nerves. Collagen types 1 and 3 degenerate in EDS. Estrogen is essential to the health of collagen. It is reasonable to assume that blocking estrogen would theoretically accelerate or heighten estrogen depletion impacting collagen regeneration and tone.
Hansen M, Kongsgaard M, Holm L, Skovgaard D, Magnusson SP, Qvortrup K, Larsen JO, Aagaard P, Dahl M, Serup A, Frystyk J, Flyvbjerg A, Langberg H, Kjaer M.
Source: Institute of Sports Medicine, Bispebjerg Hospital, and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. firstname.lastname@example.org
The knowledge about the effect of estradiol on tendon connective tissue is limited. Therefore, we studied the influence of estradiol on tendon synthesis, structure, and biomechanical properties in postmenopausal women. Nonusers (control, n = 10) or habitual users of oral estradiol replacement therapy (ERT, n = 10) were studied at rest and in response to one-legged resistance exercise. Synthesis of tendon collagen was determined by stable isotope incorporation [fractional synthesis rate (FSR)] and microdialysis technique (NH(2)-terminal propeptide of type I collagen synthesis). Tendon area and fibril characteristics were determined by MRI and transmission electron microscopy, whereas tendon biomechanical properties were measured during isometric maximal voluntary contraction by ultrasound recording. Tendon FSR was markedly higher in ERT users (P < 0.001), whereas no group difference was seen in tendon NH(2)-terminal propeptide of type I collagen synthesis (P = 0.32). In ERT users, positive correlations between serum estradiol (s-estradiol) and tendon synthesis were observed, whereas change in tendon synthesis from rest to exercise was negatively correlated to s-estradiol. Tendon area, fibril density, fibril volume fraction, and fibril mean area did not differ between groups. However, the percentage of medium-sized fibrils was higher in ERT users (P < 0.05), whereas the percentage of large fibrils tended to be greater in control (P = 0.10). A lower Young's modulus (GPa/%) was found in ERT users (P < 0.05). In conclusion, estradiol administration was associated with higher tendon FSR and a higher relative number of smaller fibrils. Whereas this indicates stimulated collagen turnover in the resting state, collagen responses to exercise were negatively associated with s-estradiol. These results indicate a pivotal role for estradiol in maintaining homeostasis of female connective tissue.
PMID: 18927264 [PubMed - indexed for MEDLINE]
Of course one solution would be to come off estrogen blockers to aid collagen in replenishing so I can better protect my myelin and peripheral nerves. And that means risking the return of estrogen receptive breast cancer. This January I will finally see a neurologist who specialises in peripheral neuropathy. So until there’s other solutions all I can do it take solace in the fact that I do probably understand what I’m dancing with here, that it is not some unfathomable mystery, and this at least makes me feel in control of this quite out of control challenge. What’s this dance been like?
CHILDHOOD CONDITIONS, DIAGNOSES AND INFO:
Was born to an alcoholic mother who had twice attempted abortion with Quinine. Recurrent infections from 6mths old including fairly constant Strep, Measles (since age 3, recurrent for 10 mths in my 30s), Herpes Simplex since early childhood and EBV since my mid 20s. Antibiotics every few months for upper respiratory tract infections until age 26 (when dx’d with food allergies, off sugar, on probiotics, anti candida program, supplements). Dx’d with primary immune deficiencies (IgA, IgG2, Complement C3, neutropenic until 2001 then fluctuating neutropenia. On prophylactic Doxycycline since Feb 2010.
Was dx’d at St Elmos Hospital (Moreland, Vic) in 1965 with autism at age 2 (then called infantile psychosis), dx’d with language processing disorder at age 9 (gained functional speech by age 11), was born with collagen disorder of Ehlers-Danlos Syndrome (diagnosed 2013) with rupturing relatives indicating type 4. Salt craving since mid childhood (on saline and ate salt daily, father also saturated his food with salt and had dizziness if he didn’t have salt). People dx’d with autism on both sides of family.
Signs of autonomic dysfunction since at least early childhood. Hypoventilation (drowned twice at age 3, could swim the length of the Olympic pool on the bottom, commonly got dizzy from not coming up for breath), hyponeas and daytime central apneas since childhood (in early teens asked why other people’s brain keeps them breathing and mine keeps forgetting).
PRE- BREAST CANCER 2009-2010
SEPT 2009-FEB 2010: 7 mths of antibiotics for treatment resistant Haemophilus (I’m IgG2/IgA deficient),. By mid 2010 reported significant worsening of life long hypoventilation/central apnea, episodes of leg collapsing and recurrent severe multiple muscle spasms (legs, diaphragm).
POST BREAST CANCER
APR-JULY 2011 Vertigo and significant increase in autonomic and mobility issues 3 mths before cancer dx
JULY 2011 dx’d with ER+ breast cancer
AUG 2011 left breast mastectomy and removal of sentinel node (right breast mastectomy FEB 2012 as cancer started as multifocal comedo which has high return rate including to unaffected breast)
SEPT- DEC 2011 4 rounds of chemotherapy (Taxotere, Cyclophosphamide)
DEC 2011-PRESENT on Tomoxifen
JAN 2012 Severely painful feet on waking with progressive stiffening and clawing of hands. Episodes of acute stabbing pains in toes. Leading up to 2nd mastectomy so no action taken.
FEB 2012 dx degenerative lumbar spinal stenosis. Brain MRI normal. 2Nd mastectomy was done.
MAR 2012 dx’d Mixed (mostly Central) Apnea. Brain & Cervical spine MRI normal. Put on CPAP (later ASV). Responded well to sodium 5000mg, added magnesium. Sleep specialist suggested I had salt wasting.
APR 2012 Cardiologist dx’d Arrythmia and O.H, added Calcium and Citruline and arrythmia improved and daytime Central Apnea and bradypnea became relatively managed.
APR 2012 thyroid function (after supplementing, incl on 5000mg sodium) and electrolytes were normal. Reported polyuria and observes high sodium seemed to reduce it. Diabetes mellitus was tested and negative. It was then presumed part of autonomic dysfunction.
JUNE 2012 reported a few weeks of sleep attacks/flushing/nausea, then it subsided. No action. Episodes of surging dull pains travelling up upper arms – episodic so took no action. Had 1st episode of acute shooting pains up the back of my head on left side followed by very sore scalp (‘Occipital Neuralgia’?)- episodic so took no action.
MAR 2013 dx’d Ehlers Danlos Syndrome (4 ruptured relatives so suspected to be type 4, the vascular type). Improved autonomic function on 8000mg sodium was taken to be part of self management with EDS/POTS.
MAR 2013 dx’d Inflammatory Tenosynovitis (of hands and feet) following MRI. Went onto Meloxicam 15mg and 14 days of Prednisolone to which it responded well. Rheumatologist ordered tests re markers for autoimmune disease/paraneoplastic syndrome (all ok) and tests to check re salt wasting. (on 8000mg sodium) serum sodium was normal and Urine sodium was in the normal range – 143mmol .Creatinine, protein both normal. eGFR 72 mL/min/1.73 (kidney function mildly impaired). Urine volumes were 1108ml and 3168ml
MAY 2013 Three days of severe back pain, presumed it was the lumbar spinal stenosis. Corresponded with nausea which I put down to the pain. The pain left after a few days but the nausea remained. ‘Sleep attacks’/somnolence with flushing recurred along with the nausea.
JUNE 2013 Sleep specialist ordered the urine and aldosterone/renin/cortisol tests repeated and ordered an MSLT test for narcolepsy. Results: Urine sodium on 8000mg sodium was now 289mmol but still not as high as expected. Creatinine and protein were normal. Kidney function again, only mildly impaired. Urine volume was 4080 ml
JUNE 2013 Came off Meloxicam (inflammatory tenosynovitis in remission) and reduced sodium to 2500mg. Developed progressively more severe polyuria, eventually up to 7L output a day (no polydipsia). D.I was ruled out following 14hr testing. Went from 59kg to 56kg on day of testing. Returned to 5000mg sodium next day and within 48 hrs weight was back at 59kg but no polyuria since.
JULY 2013 woke up in a (non-productive) coughing fit. Had three more coughing fits within 10 days, all set off by intense laughing and each time culminated in a choking episode. Lung X-Ray: normal. I still laugh but now don’t let myself get into intense laughter and now no further episodes.
SEPT 2013 had ultrasound of all major arteries as part of EDSIV screening . Vascular results all fine.
SEPT 2013 2nd episode of ‘Occipital Neuralgia’. Two days later lost sensation in end of thumb (returned), later same day lost sensation in my lips and last third of tongue. Next day severe burning sensation in lips and tongue with severe soreness and permanent ‘salt’ taste. GP who dx’d Neuropraxia/Burning Mouth Syndrome. Went on alphalipoic acid and in 4 weeks it resolved (Returned Nov)
SEPT 2013 sharp abdominal pain an inch below belly button, followed by hernia-like pulling sensation, then several weeks of what felt like uterine pains. Gynacologist’s ultrasound showed fibroids have grown, endometrium thickened (in a context of Tomoxifen) but not worrying enough yet to address. No further episodes.
SEPT 2013 progressive bone pain from the Ischial Tuberosity. After 4 weeks saw GP who dx’d Ischial Bursitis. Ongoing ever since, semi-managed with Meloxicam.
SEPT 2013 troubling clusters of central apneas (ie up to 5 min not breathing out of 9 min) and long hypopneas (up to 130 secs) lead to changing from CPAP Auto machine on to VPAP Adapt ASV machine. This resolved the clusters of centrals and the hypopneas reduced to max length so far of 60 secs. AHI is good and with VPAP insp/exp times normalised (previously insp time was double exp time, now exp time was double insp time) though EPAP (which helps with inhalation) pressures reduced from 14 (95% of the time) to 5-7 although IPAP (which helps with exhalation) went to pressures of 11-15. As a result temp dysregulation improved a lot and narcolepsy resolved completely (a GREAT relief).
OCT 2013 Increased episodic loss of sensation with legs… commonly in one or the other (since 2009 then especially since 2012), but now in both together. Ie: fell up stairs twice in a row, lost sensation followed by severe heaviness, ‘electric’ tingling running up and down legs following 30 min exercise. Noticed a few days after these episodes that a line up the sides of my thighs (and a line up the sides of my upper arms) were very sore to touch, as if bruised, and that I had lost strength in these. Inflammatory tenosynovitis in feet and hands returned (after 3 mths remission), low-moderate level at this stage as did mild nausea/vertigo (left after a week). This all coincided with being 4 weeks off Meloxicam, Q10 and Alpha Lipoic Acid=. Returned to Q10, alpha lipoic acid and increased omega 3s from 5000mg to 10,000mg… no improvement. Returned to Meloxicam and within 3-4 days had more strength in legs and arms and hands/feet less stiff, feet less sore.
NOV 2013 9/11/13 still on Meloxicam, buzzing in legs, bradypnea, flushing and stiffness returning in hands/feet. Came off Meloxicam 11/11/13, did fine until 22/11/13 (10 days) then hands/feet stiffness and pain returning together now with burning lips. Returned to Meloxicam 23/11/13 to limit progression of current PN flare. 48 hrs later, all good again.
DEC 2013 Came off Meloxicam on 7/12/13. Had 2nd sleep study 10/12/13. This confirmed there is still significantly slowed shallow breathing. Daytime episodes are also sometimes quite challenging sometimes causing dizziness and imbalance.
16/12/13 had a cold sore flare up (had these all my life and they flare one or more times a year and I used to be on Lysine before and during chemo then let it lapse when I didn’t have cold sores). This time, however, the cold sore flare up co-incided with another (though more minor) episode of ‘Occipital Neuralgia’. Started 2400mg Lysine ASAP and cold sore and ‘Occipital Neuralgia’ both subsided within days. Continued Lysine daily, however burning lips set in again on 24th Dec. Within 48 hours another, cold sore flare up. This time came along with headache, dizziness, nausea, flushing and eventually also diarrhea. Saw the GP whose opinion was that these flare ups of Herpes Simplex 1, (like being unable to get rid of my plantar warts which I’ve fought ongoing now for three years), was part of my immune deficiencies.
Noticed that since being on 2400mg lysine daily the ‘inflammatory tenosynovitis of the hands/feet reduced, the Ischial Bursitis that has been ongoing since Sept stopped having any pain whatsoever, and no significant joint stiffness either (usually all there within 7-10 days off Meloxicam/low omega 3s). All this in spite of being off Meloxicam for 21 days and only only 5000mg omega 3s. As I have IgE allergies to soy/peanut and wheat and am casein intolerant (can cope with sheep milk products but not cow’s) my diet is usually low in lysine.
JAN 2014 3/1/14 The sick headache and nausea continued along with fatigue and an eye twitch (right eye) I usually get only when very run down. I’m sleeping 1-3 hrs during the day for over a week now. Developed pain in the posterior section of the left armpit (had a reactive but negative Sentinel Node removed with the left breast in 2011). The pain was odd, stinging pain with light touch (including from the bed covers), some stabbing pain, soreness when pressed. The area effected extended several inches down the arm and several inches down my rib cage. Started back on Meloxicam and after 48 hrs the armpit area was a mixture of relative numbness and sore spots. Two days later I had a transitory episode of tingling and numbness through the whole left side of my face down my neck which then felt like it was contracting (so like a nerve thing that then triggered creeping muscle contraction). It lasted only around 30-60 min then subsided. Vertigo has restarted.
I acknowledge Aboriginal and Torres Strait Islander people as the Traditional Owners of this country throughout Australia, and their connection to land and community.