Fluoroquinolone Antibiotics Warning For Neuropathy Patients

Today's post from zedie.wordpress.com (see link below) is a very short one but is none the less important for that. Depending on the infection in your body from whatever cause, you may be prescribed antibiotics. Some of these antibiotics are called fluoroquinolones and are notorious for causing neuropathic symptoms. Very often it will be difficult to spot the name fluoroquinolone on the box because the brand and pharmaceutical names will be most prominent. If you already have neuropathy, it may be worth asking your doctor if the antibiotics he/she is prescribing belong to the fluoroquinolone family. If so, it may be worth changing them - there are plenty of alternatives. This short post talks about the American FDA requiring that drug companies place a neuropathy warning on fluoroquinolone packaging. This is of benefit to neuropathy sufferers but also patients who may be at risk of getting neuropathy.

Fluoroquinolone Labels Updated to Reflect Heightened Risk for Peripheral Neuropathy.
Author Zedie: US Virgin Islands August 16th 2013


The FDA is requiring that the labels of fluoroquinolone antibiotics warn of the drugs’ increased risk for peripheral neuropathy.

The risk has been observed with oral and injectable fluoroquinolones, but not topical agents. Patients could experience peripheral neuropathy any time during their treatment, and it could persist for months or years or be permanent.

Patients should contact their healthcare providers if they develop symptoms consistent with peripheral neuropathy in the arms and legs, including pain, burning, numbness, or weakness; change in sensation to touch, pain, or temperature; or change in the sense of body position.

Patients who develop these symptoms should stop taking the antibiotic and receive alternative therapies unless the benefit of the fluoroquinolone outweighs the risk.

Source: FDA MedWatch safety alert

http://zedie.wordpress.com/2013/08/16/fluoroquinolone-labels-updated-to-reflect-heightened-risk-for-peripheral-neuropathy/

Sexual Problems for Men with Neuropathy

This is another topic which has been covered before on the blog but recently a 50 year old man from Arkansas mailed and said that despite having both neuropathy and HIV for some years, his doctor had told him that his erectile disfunction was a result of his age and a lifetime of smoking, nothing more. This may perhaps be the case but some doctors need to realise that ED can definitely be a result of neuropathic complaints and not dismiss someone's concerns with a cliche. Losing their potency is a really big deal for many men and having a genuine medical reason for it can perversely, ease the blow. This article is from medicalxpress.com (see link below) and shows the link between ED and neuropathy revealed by the results of Spanish research in this area.

Erectile dysfunction study shows high prevalence of peripheral neuropathy
November 15, 2011

Spanish researchers have uncovered clear links between erectile dysfunction (ED) and peripheral neuropathy, according to a paper in the December issue of the urology journal BJUI.

"Up to now the impact of damaged nerves in the peripheral nervous system on ED has been underestimated" says lead author Dr Consuelo Valles-Antuña, from the Department of Neurophysiology at the Hospital Universitario Central de Asturias in Oviedo.

"However our study of 90 patients shows that men with more severe symptoms of peripheral neuropathy, which can be caused by disease, trauma or illness, had greater self-reported ED and required more aggressive treatment.

"Our findings underline the importance of clinicians carrying out neurophysiological tests on patients with ED, particularly in the pelvic area."

The research team, which included experts on both neurophysiology and urology, studied 90 consecutive patients with sexual problems recruited from the hospital's Department of Andrology.

ED was diagnosed using the five-item version of the International Index of Erectile Dysfunction (IIEF-5) and the occurrence of peripheral neuropathy was predicted using the Neuropathy Symptom Score.

A range of neurophysiology tests were carried out to assess the presence of large and small fibre peripheral neuropathy.

The researchers found that:

•The average age of the men in the study was 54 years of age. Ten per cent were under 40 and only two per cent were over 70.
•No significant correlation between IIEF-5 scores and increasing age was found. In fact, younger patients had lower (worse) IIEF-5 scores, which could be due to higher expectations or a higher number of organic risk factors.
•Just under a third of the patients (30 per cent) had cardiovascular disease, 16 per cent had neurogenic risk factors (relating to the nerves or nervous system) 16 per cent had diabetes and 11 per cent had no risk factors. Just over seven per cent had been diagnosed with mental health issues.
•Patients with more severe symptoms of peripheral neuropathy showed lower (worse) IIEF-5 scores and required more aggressive therapies.
•Neurophysiological exploration confirmed that just under 69 per cent of patients had neurological pathology. Of these, 61 per cent had some type of peripheral neuropathy and eight per cent had myelopathy - problems with their spinal chord.
•Just under 38 per cent of the patients had polyneuropathy, which occurs when a number of the peripheral nerves throughout the body malfunction simultaneously. Of these nine per cent had small fibre neuropathy, damage to the small unmyelinated peripheral nerve fibres, and just over 14 per cent had pudendal neuropathy, affecting the somatic nerve in the pelvic region.
•The findings of the sympathetic skin response tests underlined the importance of checking nerve problems in the pelvic area, as response alterations were much more common in the penis than hand or foot.
•No association between neurophysiological diagnosis and IIEF-5 scores was detected, but a statistical association was found between neuropathy and the Neuropathy Symptom Scores.
."To our knowledge, this is the first study to assess the whole peripheral nerve fibre spectrum in a non-selected group of patients with erectile dysfunction" says Dr Valles-Antuña.

http://medicalxpress.com/news/2011-11-erectile-dysfunction-high-prevalence-peripheral.html

Is There A Good Diet For Neuropathy

Today's post from the ever-reliable neuropathydr.com (see link below) looks at the best dietary options if you have neuropathy. While it doesn't explain the science behind the choices, it does seem to be based on a low gluten food base and as gluten is more and more associated with nerve problems, this may be logical. It also has to be said that this sort of diet is never easy to shop for and there may also be budgetary considerations to bear in mind, however, if we're aiming for the best possible dietary self-care then the ideas here may be useful to you when compiling your shopping lists.

Quick Guide to the Best Neuropathy Diet
Posted by Editor on July 20, 2015

This Guide Describes What to Eat Throughout the Day for a Healthy Diet!

You have no doubt heard that changes to your diet and lifestyle can have a tremendous impact on your health as far as neuropathy and chronic pain is concerned.

But what is a neuropathy diet? Exactly what you should be eating, and what should you avoid?

Here is a breakdown of a typical day’s worth of snacks and meals on the neuropathy diet to give you an idea of what kind of adjustments you should be making on your own.

Of course, you may need to modify this general outline for your own symptoms or pain level under the supervision of your NeuropathyDR Clinician.

First, be sure to have breakfast every morning. Ideally, eat a small amount of protein within a few minutes of waking up, which helps to jump-start your mental state as well as your metabolism.

You could have a protein shake made with vegetable protein powder (dairy-free) and coconut milk or almond milk. Or if you prefer not to drink your breakfast, try granola (gluten-free) or steel cut oats.

Next, you’ll want to have a small low-carb snack about three hours after breakfast. Half an apple or banana would do the trick or a small amount of nuts, such as almonds. Be careful when consuming packaged snacks, such as protein bars, as many of them contain a great deal of sugar.

For lunch, you’ll want more protein and veggies. The easiest way to do this is make a salad featuring your favorite kinds of greens—spinach is great. Add a small amount of chicken, tuna, turkey, or salmon for a lean protein, or use tofu if you’re vegan. Throw in a few walnuts or almonds and a drizzle of olive oil.

Have another snack in mid-afternoon, something small and low-carb like your morning snack.

For dinner, emphasize vegetables like asparagus, beets, squash, sweet potatoes, or cooked spinach. Avoid starchy veggies like white potatoes or rice. For a protein, try locally sourced hormone-free beef or fresh fish.

In the evening, have one more small snack. This time it can be a treat, such as one square of dark chocolate or a SMALL serving of gluten-free low-carb cookies.

You’ll also want to have lots of water throughout the day, and limited amounts of tea or coffee are okay.

You’ll notice that this diet is dairy-free, very low in sugar, and contains no bread products or junk food.

Try making a gradual shift into the NeuropathyDR diet over a period of a few days. You won’t believe how much better it makes you feel!

For more information on the neuropathy diet and other neuropathy basics, see our guide I Beat Neuropathy!

http://neuropathydr.com/best-neuropathy-diet/

Watch Out For Medications That Actually Cause Neuropathy Themselves!

Today's post from medmerits.com (see link below) is highly technical and mentions many drugs you may never have heard of but is nevertheless a very useful article. If only more experts in the field exposed dangerous drugs in this way, many people might be spared the agonies of neuropathy. However, that is easier said than done and when you think of the complexity of the drugs we use for all other conditions, it's maybe little wonder that, despite their effectiveness in treating the main target problem, one of their side effects can be nerve damage. That said, it's the job of pharmaceutical companies and doctors to protect us (or at least warn us) from hidden side effects but sometimes, the achievement of success in treating one problem can be enough to forgive the emergence of another. Take chemotherapy as one glaring example: without it the cancer may not be tackled but with it comes a significant risk of neuropathy - sometimes it's a question of which is the greater evil/benefit. In war they call it 'collateral damage'. What this detailed article does tell us is that it's always important to check and know the chemical name of the drugs we are taking, because the brand names often hide a multitude of sins, If you use various trustworthy drug interaction check sites, you will need to know the drug's proper name in order to be able to check all its potential interactions and side effects. Unfortunately, most people with neuropathy also have other medical issues and are being treated for those as well, so it's vital to be able to trust any drug combinations and at least be forewarned of any possible problems.

Drug-induced neuropathies
By Louis H Weimer MD Etiology Article section 4 of 11. 

No broad etiology or pathogenic mechanism has been suggested, but isolated cases may be part of an acute hypersensitivity reaction (Glyn and Crofts 1966). Most of the potentially pathogenic mechanisms in this section are speculative.

Specific agents.

Allopurinol. Allopurinol has been used for the treatment of gout since its approval in 1966. Allopurinol inhibits the enzyme xanthine oxidase, which blocks the metabolism of hypoxanthine and xanthine (oxypurines) to uric acid, interfering with the catabolism of purines. A number of cases of neuropathy have been associated with this agent in reports with various strengths of association (Glyn and Crofts 1966; Worth and Hussein 1985; Azulay et al 1993). The initial description included a hypersensitivity reaction with later drug rechallenge with a subsequent repeat allergic reaction, which included symptoms and signs of peripheral neuropathy. The patient also received colchicine after symptom onset with unclear timing related to neuropathy onset. Symptoms improved but persisted after cessation (Glyn and Crofts 1966). Fewer than 10 cases have been noted in the literature with at least 2 cases having complicating issues (uremia). The most recent report included some electrophysiologically and pathologically demyelinating features (Azulay et al 1993). These features were not previously noted, and regression occurred after drug cessation. Most cases occur after several or many years of therapy. No predisposition or ancillary factors are currently known. No experimental evidence supports the association, making this a possible, but not a definite, rare idiosyncratic association. In fact, the agent has been used to preserve nerve and vascular function in streptozotocin-induced diabetic neuropathy in rats (Inkster et al 2007). Inhibition of xanthine oxidase produced reactive oxygen species is the suspected beneficial effect. Blood flow declines caused by the experimental diabetes were also partially corrected.

Almitrine. Almitrine bismesylate is not FDA approved for use in the United States, but it is available in many other countries for treatment of chronic obstructive pulmonary disease and some vascular disorders including stroke prophylaxis. Almitrine acts as a peripheral chemoreceptor agonist. The component is noteworthy because it appears to commonly induce a predominantly sensory neuropathy. In 1 small placebo controlled study of 7 controls and 5 treated chronic obstructive pulmonary disease patients, 3 of 5 treated patients and none of the controls developed significant neuropathy (Allen and Prowse 1989). Bouche and colleagues reported 46 cases of almitrine-associated neuropathy in one series (Bouche et al 1989). The range of onset described is 9 to 25 months after medication onset. Sensory symptoms restricted to distal legs involving all modalities are typical. Electrophysiology and nerve biopsy findings were consistent with sensory axonopathy (Gherardi and Baudrimont 1987; Petit et al 1987). Improvement is described in most cases and is usually complete after a year (Bouche et al 1989). Numerous other reports have been made that support the high incidence of neurotoxicity with this agent (Louarn 1985; Blondel et al 1986; Petit et al 1987; Allen 1988; Wouters et al 1988; Allen and Prowse 1989; Gherardi et al 1989). Small placebo control studies have reported variable, but significant, percentages of patients stopping trials because of neuropathic symptoms. Gherardi and colleagues have reported nerve biopsy and ultrastructural studies of 8 cases. The primary finding is axonal loss of large myelinated fibers with signs of regeneration in 1 delayed biopsy. In addition, signs including segmental demyelination on teased fiber preparations suggested a demyelinating component in a variable percentage of fibers. No animal studies are available for consideration. No predisposing conditions are known. Moreover, the severity of hypoxemia from the pulmonary disease does not appear to correlate with the appearance of neuropathy or subsequent improvement after cessation. One series did describe a shorter latency to neuropathy onset in chronic obstructive pulmonary disease versus vascular patients, but most were receiving higher doses. However, some additional neuropathological signs seen in isolated cases (microangiopathy) could be secondary to chronic hypoxemia. Weight loss is commonly associated with the appearance of neuropathy. Some studies using a lower dosage (< 100 mg/day) have shown no significant neuropathy, including electrophysiologic changes (Weitzenblum et al 1992). Recent series have reported no dropout due to neuropathy of patients who used similar dosages, but these series are without specific methods to detect sensory loss.

Amitriptyline. Amitriptyline is a useful drug in the treatment of painful conditions including peripheral neuropathy, especially conditions with marked small fiber mediated pain involvement. However, several reports have associated this agent and, even more rarely, other tricyclic antidepressants including imipramine with inducing peripheral neuropathy (LeWitt and Forno 1985; Leys et al 1987). Many of the cases described are in the setting of overdose with other complications including rhabdomyolysis and cholinergic effects on the CNS and periphery; however, a small number have described suspected neuropathy on conventional amitriptyline dosages with improvement after cessation (Isaacs and Carlish 1963; Nimmo Smith and Grieve 1963; Zampollo et al 1988). There is limited experimental evidence of ultrastructural lesions in cultured neurons and astrocytes, but this relation to human toxicity is speculative at best and has not altered use in patients with neuropathy.

Chloroquine. Chloroquine is an agent used to treat malaria prophylaxis and some autoimmune conditions. The primary neuromuscular complication is a vacuolar myopathy, which can be fulminant (Siddiqui 2007); however, rare cases of neuropathy with demyelinating features and axonal loss have been described (Wasay et al 1998; Stein et al 2000). Onset is typically 1 to 2 years after starting medication and involves both sensory and motor fibers. Severity is not typically marked. Schwann cells have shown dense and laminar cytoplasmic inclusions similar to those seen with amiodarone and perhexiline, notable other causes of demyelinating toxic neuropathy. Sural biopsies have shown axonal loss and segmental demyelination and remyelination (Tegner et al 1988). Electrodiagnostic studies have also suggested a neurogenic component superimposed on the predominant myopathy. Some have noted the pattern could mimic a polyradiculopathy. This effect has been reproduced in rats.

Cyclosporin. Cyclosporin A has been used as an immunosuppressive agent in numerous conditions including organ transplantation and even some cases of immune mediated neuropathy. Limited information has associated cyclosporin A with otherwise unexplained peripheral neuropathy. The evidence rates this agent at best as a possible, but not probable, causative agent at present (Blin et al 1989; Chan et al 1996).

Dichloroacetate. Dichloroacetate is used experimentally to treat chronic lactic acidemia from mitochondrial diseases. Peripheral neuropathy is common with chronic dichloroacetate treatment. Clinical and electrophysiologic signs of sensorimotor neuropathy are found (Spruijt et al 2001; Anselm and Darras 2006; Kaufmann et al 2006). The neuropathy is significant but can be reversible over months if the drug is stopped. Neuropathy also develops in younger children with lactic acidosis but was said to be tolerated by most in one trial of 36 impaired children (Stacpoole et al 2008). The neurotoxic mechanism is not fully known, but the agent causes reversible demyelination in cultured rat Schwann cells and dorsal root ganglia neurons exposed to dichloroacetate for up to 12 days (Felitsyn et al 2007). The heme precursor delta-aminolevulinate is implicated in neurologic complications associated with porphyria and tyrosinemia type I. The compound is elevated in the urine of animals and humans on dichloroacetate and appears to damage Schwann cells in part by reducing the levels of myelin-associated lipids and proteins, including myelin protein zero and peripheral myelin protein 22 (Felitsyn et al 2008). It is currently unclear but suspected that patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) may be at increased risk of developing the toxic neuropathy. The drug is also under investigation in the treatment of glioblastoma multiforme. Dichloroacetate may help minimize treatment resistance mediated by changes in mitochondria that reduce cancer cell apoptosis in part by a switch from mitochondrial oxidative phosphorylation to cytoplasmic glycolysis. However, studies in humans have been limited by dose-dependent peripheral neuropathy (Michelakis et al 2010).

Glutethimide. Glutethimide is a sedative-hypnotic agent originally used as an ethanol substitute, but it proved to be highly addictive in its own right. The compound was reclassified as schedule II and withdrawn from general availability in 1991. Chemically, the compound is structurally similar to thalidomide, an agent that more commonly induces sensory neuropathy. Rarely, neuropathy has been associated with chronic glutethimide use at high doses (Nover 1967; Haas and Marasigan 1968). Cerebellar ataxia is also described and may be marked and persistent. Manifestations are predominantly but not exclusively sensory and are supported by limited electrodiagnostic data. Improvement or resolution over ensuing months is described. No experimental evidence or nerve biopsy data are available for correlation.

Ixabepilone. The epothilones are a new class of chemotherapeutic agent with currently low tumor resistance. The class includes the natural agents, epothilone B (patupilone) and epothilone D, which are not yet FDA approved as well as the semisynthetic analog, ixabepilone (Bhushan and Walko 2008; Swain and Arezzo 2008); ixabepilone was FDA approved in October 2007. Breast cancer is the primary indication, but phase II studies are completed or are ongoing for a variety of cancer types. The group binds to tubulin similarly to certain other chemotherapeutic agents, such as vinca alkaloids and taxanes, but at differing binding sites. Similar to taxanes, the drugs promote dysfunctional stabilization of microtubules but with a differing mechanism, in contrast to microtubular destabilizing agents such as vincristine, colchicine, and podophyllotoxin (Cortes and Baselga 2007). Peripheral neuropathy from ixabepilone is a major dose-limiting side effect. Mild-to-moderate (grade 1 to 2), predominately sensory neuropathy that improves or resolves is most common, but more severe grades (grade 3) occur rarely in monotherapy and at rates of 10% to 15% with combination therapy or in patients previously exposed to taxanes or capecitabine; grade 4 neuropathy appears to be very rare (Denduluri et al 2007; Perez et al 2007; Roche et al 2007; Thomas et al 2007a). Dose reduction may be adequate in many, but treatment discontinuation occurs as well; more dispersed treatment protocols may have lesser toxicity (Thomas et al 2007b). Twenty-one percent of patients treated with ixabepilone plus capecitabine discontinued treatment because of sensory neuropathy in one large phase III trial (Thomas et al 2007b). Severity increases with cumulative dosing, especially after an average of 4 treatment cycles. The overall neuropathy incidence varies depending on dose and coincident treatments but is as high as 67%. The reported reversibility of sensory neuropathy is surprising considering the experience with other microtubule targeting agents such as vincristine and taxanes. One patient is reported who developed significant weakness associated with neuropathy after 1 treatment cycle (Bosch-Barrera et al 2009). Review of all phase 2 and phase 3 clinical trials found a 1% incidence of severe neuropathy in patients previously untreated and up to 24% of breast cancer patients treated with other agents (Vahdat et al 2012). Carefully monitoring for neuropathy and timely dose adjustment or treatment discontinuation is advocated depending on the neuropathy severity (Swain and Arezzo 2008). Neuropathy is increasingly recognized as a dose-limiting side effect and 20% dose reduction is one proposed strategy (Valero 2013). This entity is also discussed in the section on chemotherapy-induced neuropathy.

Leflunomide. The immunosuppressive prodrug leflunomide was FDA approved in late 1998 as a disease-modifying rheumatoid arthritis treatment. It was subsequently recognized that an axonal, sometimes painful, sensorimotor polyneuropathy is associated with leflunomide (Carulli and Davies 2002; Bonnel and Graham 2004; Metzler et al 2005). Eighty cases reported to the FDA were uncovered and described (Bonnel and Graham 2004). After this report, additional series have been reported identifying numerous additional probable cases (Bharadwaj and Haroon 2004; Martin et al 2005; Kho and Kermode 2007). Bharadwaj and Haroon describe 150 prospectively tracked rheumatoid arthritis patients in India. Fifty received leflunomide either as monotherapy or in combination with other drugs. Five developed new neuropathy (10%) in contrast to 2 of 100 receiving other treatments (2%). Nerve biopsy in 3 demonstrated epineural perivascular inflammation around small and medium-sized arterioles patchily affecting large and small myelinated nerve fibers suggesting a predominant axonopathy with features of vasculitis. All showed clinical improvement and were said to become asymptomatic within 3 months, but residual nerve conduction abnormalities remained (Bharadwaj and Haroon 2004). Kopp and colleagues describe a case and suggest a potential interaction between 5-FU and leflunomide and include the possible mechanism (Kopp et al 2005). Onset is usually after 3 to 6 months of drug use, although symptoms may appear sooner. Another study compared 16 rheumatoid arthritis patients treated with leflunomide with 16 others receiving alternative disease-modifying therapies. Neuropathy symptoms scores increased in 54% of the leflunomide group compared with 8% of the others; however, electrophysiology did not correlate with clinical symptoms (Richards et al 2007). Stopping therapy within 30 days of symptom onset gives a better chance of improvement, though recovery is typically slow. Sural nerve biopsies have shown nonspecific axonal loss in most, but signs of perivascular inflammation have been described. Primary rheumatoid arthritis is an independent neuropathy risk factor often associated with vasculitis, but leflunomide reports have not generally described this type of pattern. Neuropathy incidence is higher than with rheumatoid arthritis alone or with other rheumatoid arthritis medications. One retrospective analysis found increased associated neuropathy risk with increasing age, diabetes, and the use of other potentially neurotoxic medication (Martin et al 2007). The mechanism of neurotoxicity is not known; neuropathy cases were not detected in clinical trials. The drug remains an effective treatment and efficacy appears to be similar to methotrexate and better than sulfasalazine. However, withdrawal rates are higher than methotrexate because of toxicity; peripheral neuropathy is one of several forms of toxicity (Alcorn et al 2009). Comparison of 94 rheumatoid arthritis patients treated with either leflunomide or other disease modifying agents found significant differences in quantitative cold but not vibration perception measures; leflunomide-treated patients were roughly twice as likely to have increased cold perception measures (Kim et al 2012).

A similar agent, teriflunomide, is now approved in the United States to treat multiple sclerosis. Paresthesia and peripheral neuropathy are associated with this agent as well but the neuropathy risk and incidence are not yet known. Clinical trial data suggest an incidence of 1% to 2%, but no aftermarket reports of significant neuropathy cases are known.

Lipid-lowering agents. The statin-class of cholesterol medications acts by inhibiting the rate-limiting step in cholesterol synthesis, hydroxymethylglutaryl coenzyme A (HMG CoA). The predominant neuromuscular complication with these agents is a toxic myopathy referred to as cholesterol-lowering agent myopathy, which is well appreciated by physicians and patients. An increasingly recognized acute necrotizing myositis with rhabdomyolysis associated with antibodies against the HMG CoA enzyme can develop. However, a number of cases of peripheral neuropathy temporally associated with conventional doses of simvastatin and other agents in the class have been reported (Jacobs 1994; Ahmad 1995; Phan et al 1995; Ziajka and Wehmeier 1998; Jeppesen et al 1999; Lo et al 2003). Partial or complete recovery after drug cessation is described. One report described sural biopsy data demonstrating small and large fiber axonal loss (Phan et al 1995). Several cases have serial electrophysiological studies showing sensorimotor axonal neuropathy with variable levels of subsequent improvement. No experimental model to support the effect is known. Symptom onset has been described within days to as long as several years after onset. One case described neuropathy onset after several years of treatment with lovastatin; when treatment stopped, the condition improved (Ziajka and Wehmeier 1998). Rechallenge with pravastatin, simvastatin, and later atorvastatin each caused a subacute recurrence of burning dysesthesias that improved with cessation. Similar rapid worsening with rechallenge has been noted in other reports. One speculative mechanism proposed is that inhibition of mitochondrial hydroxymethylglutaryl coenzyme A reductase causes a subsequent decrease of ubiquinone synthesis, which potentially may disturb neuronal energy utilization (Walravens et al 1989).

Thus, only the temporal association with the neuropathy development and subsequent improvement was available to support a causative link until a case control study reported by Gaist and colleagues (Gaist et al 2002). Gaist and colleagues suspected a possible link between these agents and cases of idiopathic neuropathy, despite an earlier negative United Kingdom study (Gaist et al 2001). They then conducted a much larger population-based study in 1 Danish county (465,000 inhabitants) and cross referenced a prescription registry to a national patient diagnosis registry from 1994 to 1998, when statin use in Denmark increased from 11,547 to 50,318 nationwide. Gaist and colleagues identified 1084 registered patients with a diagnosis of polyneuropathy. They excluded 492 with onset prior to 1994 or concurrent cause of neuropathy (diabetes, renal failure, monoclonal gammopathy, etc.). Only cases with clinical signs of distal, symmetric neuropathy and an adequate workup including electrodiagnostic studies were analyzed and categorized as definite, probable, or possible idiopathic neuropathy. Twenty-five controls were randomly chosen per index case. Thirty-five definite, 54 probable, and 77 possible neuropathy cases from the registry (166 total) were found. Nine had been exposed to statins including simvastatin, pravastatin, lovastatin, and fluvastatin. Odds ratios were calculated as 4.6% overall with current users of statins compared to controls and 16.1% with definite neuropathy cases compared to controls. The researchers also calculated an interesting number needed to harm measure and found, based on their odds ratios, 1 excess case of idiopathic peripheral neuropathy for every 2,200 person-years of statin use. Considered in this way, neuropathy was suggested as a more important public health concern than myopathy in patients taking statins. However, potential pitfalls complicate the study, such as whether all symptomatic neuropathy causes were in fact excluded. Examples of complicating disorders include conditions associated with statin use, such as occult diabetes, glucose intolerance, or metabolic syndrome. (Donaghy 2002); however, not all series found a clear association with statins and idiopathic neuropathy (Anderson et al 2005). Despite the rarity of the association, the large number of patients who take these medications makes the association potentially clinically relevant. Further uncertainty was raised in 2007 by the announcement at the meeting of the American Diabetes Association of the large 8-year long Australian Fremantle study of nearly 1300 diabetic patients that demonstrated significantly decreased risk of developing neuropathy in patients treated with statins or fibrates compared to untreated patients. The reduction was 35% and 48%, respectively (Davis et al 2008). Experimental evidence suggests that the statin rosuvastatin improves a mouse model of diabetic neuropathy through improved microcirculation independent of cholesterol lowering effects (Ii et al 2005). The combination of studies and evidence challenges the importance of the earlier Gaist results; statin neuropathy likely occurs but may be much less frequent than recently thought and appears to be neuroprotective in some settings.

One possible case following initiation of simvastatin rapidly developed into neuropathy mimicking Guillain-Barré syndrome; a pravastatin challenge 6 months earlier had led to milder symptoms. The combination suggested a possible hypersensitivity reaction (Rajabally et al 2004). In contrast, lovastatin attenuated nerve injury in an experimental model of experimental allergic neuritis. The effect was blocked by mevalonate (Sarkey et al 2007).

There is no supportive experimental model of the potentially toxic effects, but alteration of membrane function though inhibition of cholesterol synthesis, reduction of axon transport, and inhibition of mitochondrial function have been suggested as possible factors. Interference with selenoprotein synthesis, a well-established pathway also implicated in some hereditary muscle disorders, has been postulated to be causative but probably relates better to myotoxicity. Myopathy from severe selenium deficiency shares some features with statin-induced myopathy (Moosmann and Behl 2004).

Lithium. Lithium has been associated with neuropathy in rare cases. Isolated reports describe the onset of typical toxic neuropathy manifestations after prolonged exposure (Tomasina et al 1990); however, most reports are after acute intoxication or overdose (Brust et al 1979; Uchigata et al 1981; Pamphlett and Mackenzie 1982; Chang et al 1988; Vanhooren et al 1990; Johnston et al 1991; Merwick et al 2011; Chan et al 2012). Excessive levels can occur due, in part, to the narrow therapeutic range of the drug; moreover, neuropathic findings may be underrecognized. Some reported cases are complicated by more generalized toxicity including cerebral impairment with the neuropathy becoming evident only with subsequent recovery. Secondary infections are also problematic, raising the issue of critical illness neuromyopathy in some instances. No convincing experimental evidence is known other than an isolated report suggesting a tendency toward reduced nerve fiber area in rats chronically given lithium over control animals (Licht et al 1997). In fact, in a small series, lithium has been reported to blunt the symptoms of vincristine-associated neuropathy in both mice and humans (Petrini et al 1999). More recently, lithium pretreatment was found to attenuate neuropathy in paclitaxel-treated mice possibly by interacting with paclitaxel-related intracellular calcium signaling pathways (Mo et al 2012).

Phenelzine. Phenelzine is a rarely used monoamine oxidase inhibitor for atypical or refractory depression. Side effects such as hypertensive crises and serious reactions with other agents are well known. Rarely, this agent (but not other MAOIs) has been implicated in inducing peripheral neuropathy. Phenelzine has been shown to affect pyridoxine metabolism and reduce measurable active pyridoxal phosphate levels in humans (Malcolm et al 1994). The compound is in the same chemical class as hydralazine and isoniazid, which both reduce pyridoxal phosphate levels and can cause peripheral neuropathy. Whether this effect is clinically relevant remains to be seen. Malcolm and colleagues demonstrated pyridoxal phosphate levels reduced, on average, by half in 19 patients on phenelzine, but none developed clinical symptoms (Malcolm et al 1994). Several reports of neuropathy associated with phenelzine have been published (Heller and Friedman 1983; Goodheart et al 1991). The neuropathy is described as a typical toxic neuropathy with sensorimotor axonal involvement with predominantly sensory manifestations.

Phenytoin. Peripheral neuropathy from chronic phenytoin use has been long recognized and generally accepted. However, despite many reported patient series, the phenomenon is based on relatively few uncomplicated prospective studies. Most likely, there is a probable effect of protracted use, especially with serum levels chronically higher than 20 µg/ml (in excess of the standard therapeutic range). Peripheral neuropathy was more commonly seen early in the history of phenytoin use when doses of 500 mg/day or higher were not uncommon. However, many of the earlier series had relatively few patients on phenytoin monotherapy, and the contributions of acute reversible phenomena were not taken into account. At current dosages with monitored serum levels, peripheral neuropathy is rare and typically produces only asymptomatic examination findings or minimally discernible neuropathy after many years of therapy. The incidence of neuropathy in epileptics on phenytoin varies considerably depending on patient populations and criteria employed (Lovelace and Horwitz 1968; Eisen et al 1974; Swift et al 1981; Shorvon and Reynolds 1982; Taylor et al 1985). Several variables have been proposed as risk factors for neuropathy development, including supra-therapeutic serum levels (greater than 20 µg/ml), protracted use (less than 10 years), and low folate levels (Lovelace and Horwitz 1968; Eisen et al 1974; Chokroverty and Sayeed 1975; Shorvon and Reynolds 1982). Other series have not found any significant association with phenytoin use compared with other anticonvulsants or these risk factors (Swift et al 1981; Taylor et al 1985). Swift and colleagues found signs of neuropathy in epileptic patients on various therapies and showed a higher incidence among patients on phenobarbital (Swift et al 1981). One case with long-term chronically elevated serum levels (31 to 38.5 µg/ml) had clinically symptomatic neuropathy, and sural nerve biopsy demonstrated mild decreases in large diameter axonal number, axonal shrinkage, and secondary demyelination (Ramirez et al 1986). This patient improved clinically and on electrophysiologic studies subsequent to phenytoin cessation.

In addition, there appears to be separate acute effects on nerve function. Acute exposure to high-dose phenytoin causes reversible slowing of nerve conduction velocity. Phenytoin affects sodium permeability across neuronal membranes by stabilizing inactive sodium channels (Macdonald 1994). Phenytoin in myelinated nerve preparations produces a voltage-dependent block of sodium channels, a shift of the sodium channel inactivation curve to more negative voltages, and a reduced rate of sodium channel recovery from inactivation (Schwarz 1989). However, carbamazepine produced some of these effects as well. Several animal studies have examined the effects of phenytoin on peripheral nerve function. Acute reversible effects have been produced with reduced conduction velocity and compound motor action potentials with acute high dose phenytoin administration in rats (Marcus et al 1981) and slow velocity after several days in guinea pigs (LeQuesne et al 1976). Serum levels were higher than 50 µg/ml. This reversible phenomenon likely represents a physiologic effect but is not a model of long-term toxicity. Some degree of acute reversible effects may have complicated some prior studies that examined chronic toxicity on high dose therapy. A human report has described similar reversible symptomatic effects 3 hours after a phenytoin loading dose (Yoshikawa et al 1999). This may represent an additional acute or subacute idiosyncratic syndrome, but a separate syndrome is not well established. The acute reversible effects on nerve function are well established, but the chronic neuropathy is considered a probable association (Mann et al 2000).

Proton pump inhibitors. A rare effect of commonly used medications can be particularly problematic to resolve and substantiate. One example is the proton pump inhibitors omeprazole and lansoprazole. Rajabally and Jacob reported a 42-year-old woman who developed predominantly sensory neuropathy after 3 months of lansoprazole use (Rajabally and Jacob 2005). Some partial improvement was noted after later stopping the medication, and no worsening was seen after switching to rabeprazole and then to ranitidine. Three other cases are reported with omeprazole, 2 of which have adequate electrophysiology and clinical information (Faucheux et al 1998). Additional carefully studied examples are needed to further substantiate this possible link with medication-induced neuropathy in this widely used class of medications. No new cases have been published as of the most recent literature search since these reports despite continued widespread use of these agents. However, these agents and histamine-2 blockers may affect vitamin B12 absorption and lead to secondary neurologic complications (Lam et al 2013).

Slaughterhouse workers progressive inflammatory neuropathy. Although not technically a medication-induced neuropathy, this local toxic epidemic at several pork processing plants in Minnesota and surrounding states produced considerable activity and investigation by numerous researchers, mostly at the Centers for Disease Control (Centers for Disease Control and Prevention (CDC) 2008). Twelve workers in a swine slaughterhouse in Minnesota developed a progressive inflammatory neuropathy with symptoms ranging from acute paralysis to gradually progressive symmetric weakness predominantly in the legs from 8 to 213 days with varying severity between November 2006 and 2007. Eleven patients had evidence of axonal or demyelinating features by electrodiagnostic testing. Spinal fluid from 7 patients showed elevated protein (mean 120 mg/dl) with no or minimal pleocytosis. Ten patients had evidence of inflammation on spinal magnetic resonance imaging (9 patients in peripheral nerves or roots and 1 patient in the anterior spinal cord). Three patients with sural nerve biopsy showed mild perivascular inflammation. In summary, patients were characterized with a sensory greater than motor polyradiculopathy, predominantly at the root or distal nerve level. The CDC researchers identified that all patients were working in close proximity to swine heads. A compressed air device used to liquefy porcine brain material may have generated aerosolized brain material, which may have induced an immune neurotoxic response. Ultimately work at the Mayo Clinic led by Vanda Lennon found a complex autoantibody profile dominated by neural cation channel IgGs that most significantly affected voltage-gated potassium channels (Meeusen et al 2012).

Tacrolimus. Prograf, previously known as FK-506, is a novel immunosuppressant that is widely used in transplant medicine and for suppression of some inflammatory disorders. The agent is a macrolide antibiotic that suppresses both cellular and humoral mediated immune responses. Neurotoxicity is common in treated patients, in part, because of the relatively high doses usually given. Central toxicity is more common with a variety of findings including leukoencephalopathy, seizures, behavioral changes, headache, or other cortical signs, many of which are dose dependent. Peripheral neuropathy appears to take the form of a severe multifocal demyelinating neuropathy that resembles chronic inflammatory demyelinating neuropathy (Wilson et al 1994; Bronster et al 1995; Labate et al 2010). Patients have responded to IVIG or plasmapheresis as well.

Both cyclosporin A and tacrolimus act through inhibition of calcineurin, though by different means (tacrolimus binding protein: FKBP-12) (Snyder et al 1998). The calcineurin inhibition, through several steps, decreases IL-2 and eventually T-cell proliferation. This pathway is also the likely cause of much of the central neurotoxicity and possibly the peripheral effects. Tacrolimus also has an additional separate function through a different binding protein, FKBP-52, that acts as a nerve stimulator, increases growth associated protein (GAP-43), and is beneficial to nerve regeneration in nerve axotomy and ischemia models (Gold et al 1998; Kihara et al 2001). FKBP-52 is part of a steroid receptor complex and may represent a target for future regenerative therapies separate from the growth factor and Trk pathways. The mechanism of why, in some patients, an immune attack that resembles chronic inflammatory demyelinating neuropathy or other autoimmune neuropathy is unclear; however, the number of reported examples is small. Interestingly, tacrolimus has also been shown to have significant and potentially therapeutic neuroregenerative activity, possibly derived from a separate pathway from the immunosuppressive calcineurin inhibition--FKBP-52 binding protein (Kvist et al 2003; Gold et al 2004). Schwann cells may play an important intermediary role (Birge et al 2004). A similar agent, sirolimus, appears to have less risk of this reaction but at least 1 case is reported (Bilodeau et al 2008).

Tumor necrosis factor-alpha blockers. Tumor necrosis factor-alpha (TNF-alpha) blockers are used in the treatment of various forms of inflammatory arthritis and inflammatory bowel diseases but are also associated with inducing or worsening other autoimmune disorders including multiple sclerosis (Stubgen 2008). One agent (etanercept) has been reported to improve chronic inflammatory demyelinating neuropathy (CIDP) (Latov and Sherman 2000; Chin et al 2003). Postmarketing reporting identified 15 patients diagnosed with Guillain-Barré syndrome or Miller Fisher syndrome from 6 weeks to 2 years after starting a TNF-alpha blocker, although associated infection may be a more important risk factor (Robinson et al 2001; Shin et al 2006). One case developed acute sensorimotor neuropathy and concomitant encephalopathy (Faivre et al 2010). Richez and colleagues reported 2 cases that developed a CIDP-like illness (Richez et al 2005). One treated with etanercept for rheumatoid arthritis developed a demyelinating neuropathy 17 months later. The other received infliximab for ankylosing spondylitis and developed CIDP 3 months later. Both incompletely improved after drug cessation without specific treatment for CIDP. Infliximab is also associated with several other CIDP-like cases with underlying rheumatoid arthritis (Jarand et al 2006; Tektonidou et al 2007; Alshekhlee et al 2010) and 3 cases with underlying psoriatic arthritis, a condition which is much less likely to induce spontaneous or vasculitic neuropathy (Stubgen 2008; Eguren et al 2009). Numerous cases resembling multifocal motor neuropathy are also reported in association with infliximab (Singer 2004; Cocito et al 2005; Rodriguez-Escalera et al 2005; Paolazzi et al 2009). However, others question whether some of these cases were actually a form of vasculitic mononeuritis multiplex triggered by the infliximab (Birnbaum 2007). One case of proposed infliximab-associated immune-mediated sensory polyradiculopathy was successfully treated with intravenous gammaglobulin (Naruse et al 2013). There are additional less clear associations with mononeuropathy and axonal sensory or sensorimotor neuropathy (Jarand et al 2006). In any event, it seems that infliximab and etanercept can contribute to or trigger an immune-mediated neuropathy in some possibly susceptible patients (Kotyla et al 2007). Adalimumab is not clearly associated with chronic neuropathy but was associated with one possible Guillain-Barré syndrome case. Ipilimumab, a monoclonal antibody that is not a TNF alpha antagonist but instead blocks a natural inhibitor of cytotoxic T-cell response to cancer cells, is approved to treat melanoma and is undergoing trials for other cancer types. A case of acute neuropathy mimicking Guillain-Barré syndrome is reported; acute enteric neuropathy is also recognized (Gaudy et al 2013).

Interestingly, in light of the fluoroquinolone story discussed earlier, peripheral neuropathy associated with TNF-alpha agents was the most common adverse neurologic event reported to the Food and Drug Administration Adverse Event Reporting System (296 reports, 38.3%), exceeding central nervous system and/or spinal cord demyelination (153 reports, 19.8%) (Deepak et al 2013). The majority of reports (71%) were labeled as “possibly associated” and not higher grades of certainty.

In contrast, these agents may have other protective properties. A mouse model of bortezomib neuropathy found that upregulation of TNF-alpha was neuroprotective, possibly by limiting certain inflammatory cytokines (Ale et al 2014).

Zimeldine. Zimeldine is another agent never approved for use in the United States but available transiently as an antidepressant in Sweden, functioning as a 5-HT reuptake inhibitor with purported fewer side effects. The drug is best known as a probable precipitating factor of an outbreak of Guillain-Barré syndrome in Sweden in 1983. The drug was withdrawn from the market 18 months after introduction because of this outbreak. A subsequent Bayesian analysis concluded that the association was supported by relevant data (Naranjo et al 1990). No additional cases, however, were identified in a retrospective review of 761 patients on zimeldine reported more recently from the same region (Bengtsson et al 1994). Hypersensitivity reactions are relatively common with this agent (1.4% to 13%), raising the question of potential immune-mediated mechanisms in this phenomenon. Zimeldine appears to affect T-cell function and blunt experimental allergic neuritis in a rat model of Guillain-Barré syndrome (Bengtsson et al 1992). The risk of developing Guillain-Barré syndrome from zimeldine was estimated as increased 25-fold compared to natural incidence controls (Fagius et al 1985).

http://www.medmerits.com/index.php/article/drug_induced_neuropathies/P3

Neuropathy voices

No apologies for posting these quotations from neuropathy sufferers on various forums across the Net. If you're ever feeling that you must be the only one in the world feeling as you do; or you want to convince your friends or family that you're not making it up; read these, or make others read them too.

George:
'After a few experimental treatments, the numbness progressed to more severe pain. My feet felt as though I was walking in fire and ice at the same time; like wearing a tight sock with sand in it'.

Henry:
'One summer day in 1998, I impulsively bought a cane at an antique store. How could I have known that I would actually need it to help me walk within six months?'

Michelle:
'After a few weeks, the pain became so severe I could hardly walk. I would take my shoes off at work, but relief was fleeting, if not at all. I also became easily fatigued. I thought the cause could be a reaction to an HIV medication I had been taking for a relatively brief time'.

Rajesh:
'To describe the pain - it was steady and strong everywhere, sometimes shooting jagged flashes through me. My big toe would have jabs, feeling like swollen footballs. The warmth and circulation was fine. The best word I can describe the pain is gyrating: like the huge mixers in a bread machine, that go round and round.'

Mary:
'Of the myriad adjustments I have had to make, the one that looms largest is the loss of independence, particularly the ability to drive. It is frustrating to not be able to hop in the car and go to the grocery store, pick up prescriptions or drop in on family and friends.'

Tyrone:
'My Neuropathy started about five or six years ago. At first I thought I just stood on my feet too long or worked too hard in the yard that day and had leg aches. Well, the pain got worse as time passed and that’s when I went to the doctor the first time about the problem. Tylenol at night didn’t phase the pain. I began having leg pain constantly; all day and all night.'

Sylvia:
'I have had to do less yard work and give up some dancing time. I love to dance, but the pain afterwards is unbearable. I have to wear high heel shoes to work, but try to get the lower heels. By the end of a work day, my legs are really hurting. I don’t feel up to anything when I get home. I just want to sit down and prop my feet up.'

Andre:
'I am back on medication and hope that it will get better soon. I did try to participate in a Neuropathy study, but was unable to complete it because the medication made me sick to my stomach so much I couldn’t go to work, so I had to drop out.'

Cynthia:
'My life is definitely affected by this disease because of the pain. Sometimes it hurts so badly it makes me cry, which only makes it worse. I would ever be so happy if they could come up with a medication that actually worked and at least take away some of the pain.'

Eli:
'I retired at age 57 and came to Florida. Gradually my legs worsened. I could not sit through a meeting, opera, concert, theatre, movies, etc. My legs spoiled the whole experience for me and eventually I had to go and stand at the back of the room to finish the concert or movie.'

Peter:
'By late afternoon which we now call the “witching hour,” the pain would always escalate. It never failed and has been going on for about 6 or 7 years. About this time the words Peripheral Neuropathy crept into the doctors’ vocabulary. Also mentioned, lumbosacral radiculopathy. Medication continued with Sinemet, Neurontin and Elavil. There was no remarkable help from any of these three. Meantime, numbness continued in both legs up to the ankle and sometimes went up the leg bit.'

Maria:
'I can get around the home with a cane and have a series of high chairs and stools. I have a scooter and am able to go to the local shopping mall. I do most of my shopping on the Internet. My husband is totally blind and is in a state of denial about my pain. He doesn’t seem to understand that I don’t want to entertain visitors for meals or overnight stays.'

Al:
'Right now, I am very frustrated with my current lifestyle. I was once such an active person. I did a lot of voluntary work and I find being confined to the house very boring. If I did not have my scooter and computer, I think I would go bats. I try to maintain my sense of humour, but it is often to my detriment, especially with some members of the medical profession who feel I do not give them the deference they deserve.'

Dr Erickson Tells Neuropathy Like It Is!

Some people are very suspicious of chiropractors when it comes to treating neuropathy and in some cases, this suspicion is justified. Today's video however, is produced by a man who you can trust and is someone who this blog has featured several times before. The reason for that trust is that he provides you with accurate information that is not a prelude to promoting a clinic or a business. He knows what he is talking about when it comes to neuropathy and tells it basically, as it is. No promises of instant relief, no 'dumbing down' of the symptoms, just good, and very well explained factual information. If you are new to neuropathy, or want to listen to a very good overview of what's happening to you, or want to explain it to friends or relatives, you couldn't do much better than watching this video. It's twelve and a half minutes well-spent.

That all said, at the very end of the video is an invitation to fill in a form for 2 free visits and receive a link to watch the video in its entirety. It's entirely up to you if you want to do that but the information you have already received is so good, you may not feel the need to go any further. You can learn much more specific info about forms of neuropathy by watching other videos produced by Dr. E.

*This blog will never advertise commercial, individual services, people or institutions unless the information they give is completely unbiased, objective and useful for the neuropathy community; not simply a means of making money.

When Neuropathy Deprives You Of Sleep

Today's post from neuropathyjournal.org (see link below) talks about the much-underestimated problem of fatigue associated with neuropathy. Let's assume that your neuropathy was caused by another condition, or you are suffering from another condition anyway - the chances are that fatigue will play a part in those symptoms anyway. Add to that your nerve damage and muscular weakness and you have serious tiredness on a daily basis. It's not fair folks and other people may look at you as if you're malingering but it's the way it is and one of Lt.Col. Richardson's best pieces of advice in this article is to ignore them; accept the state of your body as being what it is and...go take a nap if you need it.
It may also be worth mentioning that we're entering holiday periods across the world and the strains on your body and mind can be considerably greater. Listen to your body and rest when it all gets a bit too much - you'll thank yourself later and others may also benefit from a rested you too😉

Fatigue in Peripheral Neuropathy
By LtCol Eugene B Richardson, USA (Retired) BA, MDiv, EdM

Unfortunately fatigue is a central part of many neuropathies and especially the immune mediated neuropathies. It is central to many other chronic illnesses that affect the body’s immune system. The causes are often complex and many.

Dr. Scott Berman, in his book Coping with Chronic Neuropathy notes in chapter VIII “Dealing with Fatigue and Insomnia” that this symptom is one of the most difficult and challenging for the neuropathy patient. Dr. Berman is a Psychiatrist, a member of the Board of Directors of the NSN and a Medical Advisor. Scott lives with untreatable CIDP.

He notes:

…that in one study looking at fatigue in autoimmune neuropathy 80% of 113 patients had severe fatigue. The fatigue was independent of motor or sensory symptoms and was rated as one of the top three most disabling symptoms. (“Fatigue in Immune-Mediated Polyneuropathies,” Neurology 53: 8 November 1999, I.S.J. Merkies, et al).


For decades in living with untreated Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Autonomic Neuropathy (AN) and Progressive Polyneuropathy due to exposure to Agent Orange in Vietnam, I can attest to the facts noted above. While other major symptoms respond to treatment with Immune Globulin (IVIg), the symptom of severe fatigue continues as one of the symptoms that responds only temporarily to the infusions followed by several days of total fatigue following infusion and then with some lessening until the next infusion.

Dr. Norman Latov in his book “Coping with Peripheral Neuropathy”, states what I have heard other neurologists share, that the fatigue we feel, first appearing as weakness, increases as the weakness (or damage) of motor nerves expands. At this point with only a few muscles doing the whole job of lifting a leg or arm or carrying on autonomic functions, the body becomes weak and eventually extreme fatigue occurs. Think of a young child who tires easily because the muscles and nerves are not fully developed and only a few underdeveloped nerves or muscles are doing the job of moving!

On the other hand, to state the obvious, pain in some neuropathies does not help us sleep. Neuropathy patients must seek medical help in finding medications or other options which works for them. The medical practitioners have increased their knowledge in recognizing the reality of neuropathic pain. These strange symptoms from damaged peripheral nerves are present in sensory neuropathies. It is become less common for these patients to be told that it is all in their ‘head’ and are finally getting the help they need.

UPDATE ON FATIGUE IF YOU ARE ON IVIG (September 28, 2016):

Learned something else with my infusion yesterday. I got talked into getting 50 or 60 grams and could not figure out why I had such increase in fatigue, both physical and mental , when I was getting this dosage as they told me that was the dose for my weight. I forgot my line that ‘my body has not read your book” and discovered it was the excess IVIg! Yesterday I had my doctor reduce my dosage to the 40 grams which I was getting previously, and wow…. less fatigue etc…. even the day after. I have had the fatigue explained away in a number of ways, and fatigue is common in chronic illness, but then yesterday I read the brochure again that came from Gammagard. Guess what is NOW listed at top of the reactions? Fatigue and malaise!!!! I am considered going down to 30grams and see if that is even better. The point here is that each of our bodies are different an the brands of IVIg are different! Fatigue is a complex subject and deserves more research and attention as this as many have stated is one of the worst symptoms of many Peripheral Neuropathies.

Impact on family and friends:

Families and friends, as we all have learned, may not understand this reality since we “look so good” and may even believe/suggest that you are just lazy or unmotivated or worse. The best thing you can do for them is to have them watch the DVD Coping with Chronic Neuropathy which will be an education about the impact of any neuropathy on our lives.

Educating yourself about neuropathy:

At any rate, fatigue is something we struggle with every day and often regulates/determines our daily activities.

While fatigue in neuropathy and other chronic illnesses is not fully understood by the experts, from a practical standpoint, here is what I have learned to do or not do in coping with fatigue. If you have found other things that help, send us a message and we will add it to the list.

1. DO NOT think negatively about fatigue, thus feeling guilty about your fatigue. Go take a nap! (See DVD “Coping with Chronic Neuropathy”).

2. Learn when your “fatigue” periods occur, as these often establish a pattern at certain times of the day. Then go lay down and stop moaning about it, as it is what it is until it isn’t.

3. I have learned that you do not even have to actually “sleep”, but just allowing your body to rest/stop for an hour takes care of the exhaustion as the body recovers. But whatever works for you, do it without guilt or apology.

4. For nighttime, have a standard bedtime routine in preparing for sleep that tells your body that it is time to sleep.

5. Do not eat a large meal just before bedtime or take a stimulant that keeps you awake or might interfere with sound sleep (i.e. caffeine, for some alcohol).

6. Do consider drinking a glass of milk as for many this encourages the body to sleep.

7. Do consider one of those special recordings of quiet music or rain falling or similar if it helps.

8. Do consider using a ticking clock if that helps. As a child in the 40s I got my best sleep on the floor in front of the big radio in the living room listening to Dragnet or was it the Lone Ranger, maybe the Big Story. Today most TV programs have the same effect, sleep! Pun intended.

9. Muscle spasms and/or restless leg can make sleeping difficult and rob you of needed sleep. Speak to your doctor and have tests done for calcium, salt, potassium levels and other deficiencies which can make it difficult for muscles to work properly. This is especially true if you are on a diuretic which can empty your body of needed minerals. Getting up and having a glass of orange juice worked for my mother and works for me. If the lack of something is not the problem, have the doctor find out what may be causing these muscle problems. There are also medications to help prevent these muscle spasms and cramps for they are very common in neuropathy.

10. I have found that if I wake up with my mind creating solutions to an issue or writing poetry (happens) and not able to sleep, I go to another room or go do some work on my computer (write out the solution or poetry) until I begin to feel sleepy again. It works for me.

11. For some insomnia is a real curse. There are medications that one can use as Dr. Scott Berman mentions in his book, so speak to your doctor. Frankly, I would work on natural solutions first and be creative to see what works for you. But if ALL else fails these medications may help and be a heaven sent blessing.

12. My Nurse told me that many patients with this effect of a chronic illness, take Folic Acid and it is known to help. So you many want to speak to your doctor in this regard.

13. Dr. Erika Schwartz, M.D. (national leading expert on wellness) suggests that patients with extreme fatigue have the physician check your basal metabolic rate and your thyroid function. Low thyroid is a common cause of fatigue. So speak to your doctor in this regard.

14. So what do you do or not do that helps? Send it to us and we will enter it here!

DISCLAIMER: The information in this article and on the website or the links or in the guidance provided is intended to be educational and informative and not medically prescriptive or diagnostic. All patients are encouraged to consult with their own medical doctor when considering any this information.

Copyright – 2014-2015 Network for Neuropathy Support, Inc., 501c3, dba as Neuropathy Support Network. This article or its contents may be reprinted or published for educational purposes as long as the printing or publishing is not for profit and acknowledgement is granted the author.

https://www.neuropathyjournal.org/fatigue-in-peripheral-neuropathy/

Downward Facing Dog For Neuropathy

Today's post from informationaboutdiabetes.com (see link below) talks about Yoga for neuropathy. When even fully fit people can struggle to master even basic yoga positions, the idea that it can be of benefit to neuropathy patients may seem a little far-fetched (or even downright impossible). However, this short article gives you three yoga poses that may well help with the symptoms. Clearly explained, if you're still not sure what you're supposed to do, look them up on Google images and all will become clear. Worth a try? What have you got to lose?

Yoga For People With Neuropathy 
By Jacqueline Marshall, Jun 11, 2015

Do not let pictures of yoga experts with their bodies twisted into bizarre, compact shapes fool you.

Even people with stiff muscles, creaky joints, problems with balance, tingling, or numbness can perform yoga asanas or poses.

Most poses can be altered to suit anyone’s flexibility and strength level, and many help relieve the distressing symptoms of peripheral neuropathy. The yoga video series by Peggy Cappy called Yoga For the Rest of Us is an excellent way to get gentle, effective yoga instruction—modified for health issues.
Three Poses for Neuropathy

Here are three yoga postures that can diminish neuropathy symptoms, calm the nervous system, and increase mental focus.

Knee To Chest

This pose strengthens muscles that might have been weakened by neuropathy, and massages the abdominal organs.
Lie on your back, legs outstretched, arms at your sides, toes pointing up.
Bring the right knee to your chest and grasp its shin with both hands, or the forearms.
Slowly lift your head, bringing the forehead to the knee; hold this position several moments, and keep breathing.
Lower your head and leg back to the floor; repeat with the left leg.
Repeat the exercise two to four times.

Gentle Toe Stretch

Try this pose to relieve numbness and tingling in the feet. It increases foot circulation and toe flexibility.
Sit on the floor in a cross-leg position.
Thread your left hand fingers between the left toes, and right hand fingers between the right toes.
Spread your fingers apart to give the toes a gentle stretch.
Hold the toe stretch for a few moments - continue to breath - then relax your fingers.
Repeat several times.

Downward Facing Dog

Inverting the body strengthens core muscles, stimulates the endocrine system, and soothes the central nervous system. It may relieve joint pain or stiffness, and ease the numbness of neuropathy.
Start on your hands and knees, wrists directly under the shoulders, knees directly below the hips, bottoms of the toes on the mat or rug.
Press with the palms and lift your knees off the floor; slowly straighten the legs until your body forms the outline of an “A.” (If you cannot straighten your legs, it is okay to keep them bent.)
Imagine your hips and thighs are being pulled backward from the top of the thighs.
Continue breathing, gaze between the legs or toward your abdomen, and hold this position as long as you comfortably can.
Slowly bend your knees and come back to the starting position.

Talk to your doctor before starting a new exercise regimen such a yoga, especially if you have been a long-time couch potato, or have back, neck, and joint problems. You should feel a stretch when doing yoga poses, but never push yourself to the point of pain.

Source: Molecular Lab USA

http://www.informationaboutdiabetes.com/lifestyle/lifestyle/yoga-for-people-with-neuropathy

Sleep Deprivation And Neuropathy

Today's post from beating-diabetes.com (see link below) is aimed at diabetics with neuropathy but applies to all of us living with nerve problems. It talks about a problem that millions of people with neuropathic symptoms have and that is sleep deprivation. You don't need telling how important a good night's rest is for your general health and feeling of well-being and if the symptoms of neuropathy regularly disrupt your sleep it can affect your whole life, leading to all sorts of problems during the waking hours. This article gives some very helpful advice as to how to tackle the problem. The solution doesn't always lie with prescription sleeping pills; there may be other ways of improving what can seem an insurmountable problem. Lack of sleep is a vastly underrated aspect of living with neuropathy and all good advice is welcome.
 

Diabetic Neuropathy and Sleep
Written By: Paul - May• 11•14

Diabetic neuropathy can develop into a nagging intrusiveness that will undermine you ability to enjoy a good night’s sleep. And lack of sleep will exacerbate the painful symptoms of neuropathy. What can you do about it?

Peripheral neuropathy is damage to the nerves in the feet and legs. When it is caused by long-term diabetes it is called diabetic neuropathy.

This nerve damage can cause a loss of feeling in the feet or symptoms such as tingling, numbness, burning, and pain. These symptoms come and go and can be quite intensive and disturbing from time to time.

It is permanent, so once it’s happened you cannot improve it by controlling your diabetes better. However, you can allay the symptoms (and prevent the damage getting worse) through a change in diet and exercise.
Sleep disturbances

As it can be very intrusive, neuropathy can disturb your sleep in a number of ways.

The pain and weird sensations (especially in the legs) of neuropathy can make it hard to fall asleep.

Many people find themselves focusing on their pain during the evening when daytime distractions are at a minimum which makes it more difficult to get to asleep. The pain can also kick in during the night and wake you up.

Neuropathy has been linked with sleep apnoea syndrome, ie pauses in breathing during sleep.

A meta-analysis published online in late 2013 by three Japanese researchers indicates that patients with diabetic neuropathy are twice as likely to have apnoea compared to diabetic patients who do not have neuropathy. This, however, does not mean that neuropathy is a cause of sleep apnoea.

The relationship between neuropathy and sleep is a two-way street. While neuropathy can cause your sleep to be disturbed, sleep that is disturbed (for other reasons) can make the symptoms of neuropathy worse.

In addition, being deprived of sleep can lower your pain threshold and your ability to tolerate pain, which makes your neuropathic pain feel worse.
Overcoming the effects of neuropathy on sleep

There are several things you can do to overcome the intrusiveness of neuropathy:

[1] You can use medicines, both over-the-counter and prescription medications. However these can cause drowsiness during the day, as well as other side affects and can cause dependency.

[2] You can try non-pharmacological treatments such as cognitive behavioural therapy, relaxation techniques, stress management, and acupuncture.

[3] You can follow the tips below for getting a good night’s sleep. This is probably the best thing you can do.
Getting a good night’s sleep despite your neuropathy

There are several things you can do to get a good night’s sleep. You may find some or all of the following useful: 

Keep your blood glucose under control using diet and, if necessary, medications.

Get some exercise every day.

Go to bed at about the same time each night so you adhere to a regular sleep/wake schedule.

Make sure your bed is large and comfortable with a good mattress and supportive pillows.

Elevate the bed sheets so that they are not in direct contact with your legs and feet. You can do this using wire frames to create a tunnel for your feet under the blankets.

Ensure your room is cool (18 degrees Centigrade) and well ventilated.
Sleep in the dark in a noise free room (or use a blindfold and/or ear plugs).

Develop a bedtime ritual (eg, taking a warm bath, reading light material).

Limit or eliminate caffeine four to six hours before bed and minimize daytime use.

Avoid smoking, especially near bedtime or if you awake in the middle of the night.

Avoid alcohol and heavy meals before going to bed.

Turn off your TV, smartphone, iPad, and computer a few hours before your bedtime.

Adopt relaxation techniques to help induce sleep such as setting an hour aside before bedtime to relax and unwind. Try meditation or deep breathing exercise.

http://beating-diabetes.com/index.php/diabetic-neuropathy-and-sleep/

New Guidelines For Treating Painful Neuropathy

You know by now that when an article talks about diabetic neuropathy, unless it's discussing blood sugars or other specific diabetes issues, you can more or less apply the information to all forms of  sensory neuropathy. The causes may be different but the symptoms pretty much apply to all. Today's article comes from depressionforums.org (see link below) and discusses the very interesting guidelines issued by the American Academy of Neurology. It's good to see that they advise the use of the traditional neuropathy treatments "if clinically appropriate". This article was written in April, 2011 and therefore a year before Pfizer withdrew Lyrica (Pregabalin) promotion for diabetes and HIV-related neuropathy - the message is that doctors should always prescribe drugs "if clinically appropriate" and not just as a matter of course.

New AAN Guidelines on Painful Diabetic Neuropathy
Susan Jeffrey April 11, 2011 (Honolulu, Hawaii)

 — The American Academy of Neurology has released new guidelines on the treatment of painful diabetic neuropathy (PDN).

The document provides evidence-based guidance on use of a range of pharmacologic agents, including anticonvulsants, antidepressants, opioids, and others, as well as nonpharmacologic treatments, such as transcutaneous electrical nerve stimulation (TENS) and magnetic field treatment.

"We were pleased to see so many of the pain treatments had high-quality studies that support their use," said Vera Bril, MD, from the University of Toronto, Ontario, Canada, lead author of the guidelines. "Still, it is important that more research be done to show how well these treatments can be tolerated over time, since diabetic nerve pain is a chronic condition that affects a person's quality of life and ability to function."

The guidelines are published online April 11 in Neurology and were presented here at the American Academy of Neurology 63rd Annual Meeting. They were developed in collaboration with the American Association of Neuromuscular and Electrodiagnostic Medicine and the American Academy of Physical Medicine and Rehabilitation; the document will appear in the April issues of their respective journals, Muscle and Nerve and PMR.

Unreported, Untreated
It is estimated that PDN affects 16% of the more than 25 million people who have diabetes in the United States, the authors point out. The condition is "often unreported and more often untreated, with an estimated 2 out of 5 cases not receiving care," Dr. Bril noted.

"As we emphasize the use of evidence-based guidelines to treat different disorders, it becomes clear that this field is very confusing because of the volume of literature," Dr. Bril told a press briefing here. "So the guidelines have been developed and will provide a framework for physicians to use when treating their patients. Physicians can understand what the evidence is for the treatments they'll use; when there is evidence, when there isn't, or when the evidence is negative."

The process started in 2007, with more than 2200 papers on PDN; of these, 463 were deemed relevant to the guidelines. Author teams reviewed these papers and identified 79 considered "highly pertinent" to the guideline. Each of these reports was rated by teams of 2 with regard to class of evidence for effectiveness, and disagreements were arbitrated by a third member.
The only drug to earn a "Strong Evidence, Level A" rating was pregabalin, but several drugs and nonpharmacologic interventions met criteria for "Moderate Evidence, Level B" endorsement.
That only 1 drug met this level of evidence was a bit of a surprise, Dr. Bril noted. "One of the big factors that moved a study from class I to class II is that you needed at least 80% of the people in the study to complete the study," Dr. Bril said, and 2 class I studies were required for a Level A recommendation.

"I can tell you there was discussion internally about the rules because of the way it fell out, but it would be a little strange to be changing your rules for guidelines because of the findings in 1 guideline process," she said. "The others are Level B mostly because they didn't get 80% completing their studies."

The level of evidence is not driven by the effect size of the drug, she noted. "So pregabalin has a small effect on pain, but the studies were class I, and you could say people tolerated the treatment and stayed in" the pregabalin studies, Dr. Bril added. "So you can't make assumptions and change the rules because of what you're finding."
They also provide the recommended doses of agents considered useful in the document.

Strong Evidence (Level A)

• Pregabalin should be offered "if clinically appropriate."

Moderate Evidence (Level B)

• Anticonvulsants gabapentin and sodium valproate should be considered for PDN treatment. The authors note though that because valproate is potentially teratogenic, it should be avoided in diabetic women of child-bearing age, and due to its potential adverse effects of weight gain and worsening of glycemic control, "this drug is unlikely to be the first treatment choice for PDN."
• Anticonvulsants oxcarbazepine, lamotrigine, and lacosamide should probably not be considered.
• Antidepressants amitriptyline, venlafaxine, and duloxetine should be considered; however, "data are insufficient to recommend one of these agents over the others," they note.
• Opioids dextromethorphan, morphine sulphate, tramadol, and oxycodone should be considered for the treatment of PDN, they note. Again data were insufficient to recommend one of these over the others.

They note that the use of opioids for chronic nonmalignant pain has "gained credence over the last decade due to the studies reviewed in this article." Both tramadol and dextromethorphan were associated with substantial adverse events, including sedation with both agents and nausea and constipation with tramadol. The use of these agents can also be associated with development of novel pain syndromes, such as rebound headache, the authors note, and long-term use can lead to tolerance and frequent escalation of dose.

• For other pharmacologic interventions, they recommend that capsaicin cream and isosorbide dinitrate spray be considered to manage PDN, although they note that many patients can be intolerant to the adverse effects of capsaicin, which include burning pain on contact with warm or hot water or in hot weather.
• Clonidine, pentoxifylline, and mexiletine, on the other hand, should "probably not" be considered for use.
• For nonpharmacologic treatments, they recommend that use of TENS be considered but "probably not" electromagnetic field treatment, low-intensity laser treatment, or Reiki therapy.

Weak Evidence (Level C)

• They found weak evidence that adding venlafaxine to gabapentin may provide a better response and that the Lidoderm patch may be considered to treat PDN.

Insufficient Evidence (Level U)

• The authors found insufficient evidence to "support or refute" use of the anticonvulsant topiramate; the antidepressants desipramine, imipramine, and fluoxetine; or the combination of nortriptyline and fluphenazine.
• Similarly, there was insufficient evidence either way on the use of vitamins and α-lipoic acid or the combination of amitriptyline with electrotherapy for treatment of this condition.

Placebo Effect
In their summary document, the authors point out as "notable" that the placebo effect varied from 0% to 50% pain reduction in the studies reviewed for this guideline.
"The panel recognizes that PDN is a chronic disease and that there are no data on the efficacy of the chronic use of any treatment, as most trials have durations of 2 to 20 weeks," they write. "It is important to note that the evidence is limited, the degree of effectiveness can be minor, the side effects can be intolerable, the impact of improving physical function is limited, and the cost is high, particularly for novel agents."
Neurology. Published online April 11, 2011.

 Author(s)

Susan Jeffrey

Susan Jeffrey is the news editor for Medscape Neurology & Neurosurgery. Susan has been writing principally for physician audiences for nearly 20 years. Most recently, she was news editor for thekidney.org and also wrote for theheart.org; both of these Web sites have been acquired by WebMD. Prior to that, she spent 10 years covering neurology topics for a Canadian newspaper for physicians.

http://www.depressionforums.org/depressive-diseases-health-disorders/178-chronic-pain-depression/2275-new-aan-guidelines-on-painful-diabetic-neuropathy

Its Like Lightning Personal Neuropathy Blog

Today's post from finless.blogspot.com (see link below) is another personal story of life with neuropathy and the various diagnoses that this person meets along the way. Personal stories like this are often the most powerful because they remind readers that they're not alone in how they're feeling, regarding the strange things that neuropathy does to their bodies. Well worth a read if you think you've got it bad!

It's Like Thunder...LIGHTNING...in my veins?? 

Posted by Davee Thursday, July 3, 2014

Good morning! I’ve decided to use my blog not only to writing, music, and other facets of entertainment, but, also to share my journey. I’ve had significant health problems for almost two years. Initially, my rheumatologist diagnosed me with systemic lupus (SLE) on June 19, 2013. However, the medication wasn’t working and I kept getting worse and developing new symptoms. So, after second, third, and fourth opinions, my neurologist believes instead I have fibromyalgia.

In April 2014 I visited yet another rheumatologist who I hoped would be familiar with autoimmune disorders. Following an extensive intake during my initial appointment, I found a place where the doctor also listened to me. Based upon my blood work, the doctor believes I have Sjogren’s Syndrome. She also made the diagnosis of Fibromyalgia and pre-lupus. I’ve never heard of pre-lupus, but, hopefully it stays in the “pre” category.

Thank you for listening, each week I will have a new installment chronicling my journey- Which is now more frustrating than ever. I test positive for ANAs in my blood, but, the lupus tests are negative. There are several varieties of autoimmune disorders, with different caveats and health variations. Learning to live with the unknown has become my routine.

It's like LIGHTNING struck my insides...

EEEEEK!

I also write fiction books and research at least one thing for each of my writings. I want to be as accurate as possible when talking about history, illnesses, dates, geographic areas....etc, but, you get my drift. In one of my recent books, I had characters who were struck by lightning. In order to get an accurate appraisal of the medical symptoms, longer term problems, or delayed symptoms, I turned to the internet.

Lightning is primarily an injury to the central nervous system, often with brain and nerve damage. Including muscle soreness, headaches, nausea, mild confusion, memory slowness, mental fog, and dizziness or balance problems.

HUH?

How interesting that the majority of the issues occurring with me involve my nervous system. It seems that I was struck by lightning and didn't know it...NAH.

It did get me thinking about why this would happen . What is going on within my body that's causing my nerves to misfire? I had horrible neuropathy all over my body. At times it felt like pin pricks everywhere. My lips and tongue would also go numb. I would occasionally lose feeling in my shins and forearms as well. At one point, I thought I was having a stroke and my doctor even instructed me to go to the emergency room.
(Thankfully, I was not having a stroke.)

The longer term problems are even more ironically similar:
Problems processing new information
Difficulty accessing old information
Slower reaction time
Distracted
Irritable and possible personality changes
Inattentiveness or forgetfulness
Headaches such as migraines
Chronic pain from nerve injury
Tinnitus
Difficulty sleeping - either sleeping excessively or insomnia

I suffer from each item on the longer term problem list. This list further proved to me that maybe studies could combine persons with chronic nerve injuries for treatment possibilities. I'm not sure if this is already occurring, but, it might be a good start. I know I currently take 3 different meds to make life bearable, but, it would be great not to rely on such drugs.

Progressing further in research, I discovered the delayed symptom list:
Personality changes/isolation
Irritability and embarrassment at not remembering people, job responsibilities, and key information
Difficulty carrying on conversation
Depression
Chronic pain ad headaches

BINGO YAHTZEE again!

I can no longer multi-task and I still grieve over it. I used to be the go-to girl. I could juggle several projects at once and it was a piece of cake. Now, I can't even load a dishwasher and keep up with a conversation! no joke
I've experienced depression, anxiety, and anger at the limitations this auto-immune disease has forced upon my life. I'm not the same woman and it hurts, mentally.

I have to take meticulous notes and my co-workers know I will need everything in writing. Sometimes I miss critical elements of a project, and I've asked my team leader to review all my work.

It's debilitating and it worse than sucks.

Maybe I can make it more interesting and say I was struck by lightning.

It's worth a shot.
 
 http://finless.blogspot.com/2014/07/its-like-thunderlightningin-my-veins.html?zx=5581fe1246b22b0b