Therapy For Peripheral Neuropathy Research Articles

Decrypting the multifaceted peripheral neuropathy based on molecular pathology and therapeutics: a comprehensive review.

Peripheral neuropathy (PN) is a multifaceted complication characterized by nerve damage due to oxidative stress, inflammatory mediators, and dysregulated metabolic processes. Early PN manifests as sensory changes that develop progressively in a "stocking and glove" pattern. A thorough review of literature has been done to find the molecular pathology, clinical trials that have been conducted to screen the effects of different drugs, current treatments and novel approaches used in PN therapy. Diabetic neuropathy occurs due to altered protein kinase C activity, elevated polyol pathway activity in neurons, and Schwann cells-induced hyperglycemia. Other causes involve chemotherapy exposure, autoimmune ailments, and chronic ethanol intake. Symptomatic treatments for neuropathic pain include use of tricyclic antidepressants, anticonvulsants, and acetyl-L-carnitine. Patients will have new hope if clinicians focus on novel therapies including gene therapy, neuromodulation techniques, and cannabidiol as an alternative to traditional medications, as management is still not ideal.

Recent Advances in Diagnosis and Therapy of Peripheral Neuropathy

Recent Advances in Diagnosis and Therapy of Peripheral Neuropathy

Cryocompression Therapy for Peripheral Neuropathy in Patients With Multiple Myeloma

Cryocompression Therapy for Peripheral Neuropathy in Patients With Multiple Myeloma

Ultrasound-Guided Peripheral Nerve Injection Techniques.

Peripheral nerves are well seen using ultrasound (US) imaging, making US an ideal modality for image-guided nerve injections. This article provides a technical guide for common upper and lower extremity peripheral nerve injections, including the median, ulnar, and radial nerves in the upper extremity and the lateral femoral cutaneous, sciatic, common peroneal, tibial, and sural nerves in the lower extremity. US is an effective modality for use in common upper and lower extremity peripheral nerve injections. With correct technique, peripheral nerve injections can be performed safely and are useful for both diagnostic evaluation of and therapy for peripheral neuropathy.

Diagnosis and therapy of peripheral neuropathy

Diagnosis and therapy of peripheral neuropathy

Therapy-related peripheral neuropathy in multiple myeloma patients.

This review discusses the most common issues concerning multiple myeloma (MM)-related peripheral neuropathy (PN). This is an important MM complication, observed in up to 54% of newly diagnosed patients, caused by the disease itself or its treatment. Although its aetiology is largely unknown, a number of mechanisms are suspected. It is important to know the neurological status of a patient, as many new antimyeloma medicines can trigger or exacerbate any pre-existing neuropathy. Examples include thalidomide-induced and bortezomib-induced PN (TiPN and BiTN, respectively), which are key MM treatment options. TiPN is usually sensory and sensorimotor, whereas BiPN is typically sensory. The mechanisms of chemotherapy-induced neurotoxicity in MM are well known; thalidomide seems to induce PN through its antiangiogenic properties, whereas bortezomib neurotoxicity is connected with disrupted calcium homeostasis. TiPN incidence ranges from 25% to 75%, and its prevalence and severity appears to be dose-dependent. BiPN incidence is almost 40% and is dose-related as well. Poor (25%) reversibility of TiPN prompted the recommendations for dose and exposure reduction, whereas BiPN cases are mostly reversible (64%). Peripheral sensory neuropathy is very rare in patients receiving bendamustine monotherapy. Because of this favourable toxicity profile, bendamustine may be considered a promising option for combination therapies in pre-existing PN in myeloma patients. Considering the lack of curative therapy for treatment-emergent PN, prevention is a key management strategy in MM patients. All patients should be evaluated for PN before the administration of a neurotoxic drug, and those under treatment should be closely monitored by a neurologist.

Challenges in developing novel therapies for peripheral neuropathies: a summary of The Foundation for Peripheral Neuropathy Scientific Symposium 2012

On March 14-16, 2012, The Foundation for Peripheral Neuropathy organized a scientific meeting that brought together basic and clinical scientists studying peripheral neuropathies and mechanisms of axonal degeneration and representatives from the drug industry, National Institutes of Health, and Federal Drug Administration. This meeting summary covers the main discussion points laid out by the participants that hamper development of novel therapies for peripheral neuropathies and neuropathic pain. In each section of the meeting, the discussion was led by a keynote talk and was followed by a panel of discussants that were asked to bring two key questions in their areas of research. With audience participation, this format led to a lively discussion that pointed out the deficiencies in both animal modeling of human diseases and issues in clinical trial design unique to the peripheral neuropathies and neuropathic pain.

A Pilot Study of Acupuncture in Treating Bortezomib-Induced Peripheral Neuropathy (BIPN) in Multiple Myeloma (MM) Patients.

AbstractAbstract 3168 Background:Peripheral neuropathy (PN) is the dose-limiting toxicity of bortezomib in MM patients, affecting >30% patients, including painful PN. Treatment is mostly supportive with narcotics, antidepressants, and anticonvulsants. Acupuncture has been reported to be effective in treating neuropathic pain in diabetic and cancer patients. Methods:We initiated a pilot study to assess the feasibility, safety and efficacy of acupuncture in reducing the severity of BIPN in MM patients. Patients had acupuncture twice weekly for 2 weeks, weekly for 4 weeks, and then biweekly for 4 weeks. All patients continued their prescribed PN medications. Clinical Total Neuropathy Score (TNSc), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire and Neuropathy Pain Scale (NPS) were used to assess patients at study entry and week 1, 2, 3, 4, 5, 6, 8, 10 during and after 4 weeks of completion of therapy. Serum was obtained from the patients at baseline, right after first acupuncture and before acupuncture session on week 2, 4, 8, and at follow up visit on week 14. Serum samples were used to measure cytokines concentrations. Before and after acupuncture treatments, a complete neurological examination was performed. Nerve conduction studies at baseline and end of study were conducted. Treatment included insertion of disposable sterile acupuncture needles, which retained for 25 minutes, at the following points: bilateral ear points: shen men, point zero, two auricular points where electro-dermal signal was detected, and bilateral body acupuncture points: LI4, SJ5, LI11, ST40, and Ba Feng in upper and lower extremities. Results:From May 17, 2011 to February 28, 2012, 27 MM patients were enrolled in the study. Thirteen patients were women; median age was 63 years (range: 49–77); nine were black, one Asian, 17 Caucasian, and eight had diabetes. All patients had grade 2–4 sensorimotor PN: grade 2 (n=12), grade 3 (n=14), and grade 4 (n=1); 8 had painful PN. All patients had persistant PN despite discontinuation of bortezomib for a median of 19 months (range: 1–83). Eight patients were enrolled within 6 months of stopping bortezomib, all of them had grade 3–4 painful PN. Median time from diagnosis of MM to study entry was 30 months (range: 5–178). Nineteen patients were in remission and eight had progressive disease. MM therapy at study entry and through the follow up period included: revlimid (n=12), carflizomib (n=2). Therapy of PN included narcotics (n=13), gabapentin (12), amitriptyline (n=3), pregabalin (n=2), and duloxetine (n=2). Two patients withdrew after first acupuncture treatment. Twenty-five patients were evaluable for response after completion of 3 weeks (n=2), 6 weeks (n=2), 9 weeks (n=1) and 10 weeks of acupuncture (n=20). There were no adverse events associated with the acupuncture treatment. All but five patients maintained the same dose of pain medications throughout the study. Fourteen patients (56%) reported improved daily functions (e.g. walking and coordination). Ten patients (40%) reported > 50% decrease in average NPS during treatment (week 1–10). Seven patients reported 50% reduction in FACT/GOG-Ntx total scores. The decrease in NPS and FACT/GOG-Ntx, was statistically significant between baseline assessments through week 14; p-values are 0.001 and <0.0001, respectively. On the other hand, TNSc scores, an objective clinical assessment, did not significantly change. Of fifteen patients who had nerve conduction studies, five showed >10% increase in motor nerve amplitude but there was no correlation observed between symptoms/function improvements and nerve conduction studies. At week 8, one of the measured cytokines: Brain-Derived Neurotrophic Factor (BDNF) significantly increased from baseline (p=0.043). This increase was no longer significant at week 14 follow up. Conclusions:Acupuncture is safe and effective in treating persistent moderate to severe BIPN, with improvements of patient reported outcomes, pain and function. The increased BDNF during acupuncture treatment suggests that acupuncture may work through promoting survival and growth of neurons, a lengthy process that may explain the lag of significant objective clinical improvement in the short follow up of our patients. The mechanism of acupuncture working through BDNF to treat PN warrants further evaluation. Disclosures:No relevant conflicts of interest to declare.

Neurotoxicity of bortezomib therapy in multiple myeloma: A single‐center experience and review of the literature

Bortezomib is active in heavily pretreated multiple myeloma patients; the dose-limiting toxicity is peripheral neuropathy (PN). The authors retrospectively reviewed the incidence, severity, and risk factors for PN in 78 patients who received bortezomib. The median age was 57 years (range, 33-80 years), 62% of patients were men, and 37% of patients were African Americans. Seventeen patients (22%) had diabetes mellitus (DM), and 66 patients (85%) had received thalidomide. Before bortezomib treatment, 37% of the patients reported subjective, grade 1 or 2 PN. Patients received bortezomib alone (n = 10 patients) plus dexamethasone (n = 36 patients) and thalidomide (n = 20 patients) or chemotherapy (n = 12 patients). PN affected 52% of patients, including grade 3 and 4 PN in 15% and 7%, respectively. Twelve patients stopped bortezomib because of side effects that included PN (n = 9 patients), diarrhea (n = 2 patients) and cytomegalovirus pneumonia (n = 1 patient); 11 patients had dose reductions because of PN. Grade 4 PN affected 6 patients (sensory, n = 4 patients; motor/sensory, n = 2 patients). The onset of grade 4 PN was sudden rather than cumulative. Factors that were predictive of PN grade were baseline PN (P = .002), prior thalidomide use (P = .03), and the presence of DM (P = .03). Multiple myeloma responses included complete, near complete, and partial responses in 5% of patients, 10% of patients, and 27% of patients, respectively. Responses were independent of PN and of whether bortezomib was combined with chemotherapy or thalidomide. Patients remained on therapy longer for a median of 5 cycles (range, 2-36 cycles) when they received bortezomib plus thalidomide versus 3 cycles (range, 1-19 cycles) for the other combinations. PN therapy was mostly supportive. It was noteworthy that 6 of 9 patients with PN who received lenalidomide as salvage therapy after bortezomib had significant improvement in their symptoms. The risk of bortezomib-related PN was greater in patients who had PN and DM at baseline. The authors concluded that an unexpected, symptomatic improvement of PN on lenalidomide is worth further investigation.

Neurotoxicity of Bortezomib Therapy in Multiple Myeloma (MM): A Single Center Experience.

Bortezomib has demonstrated activity in heavily pretreated MM patients. The dose limiting toxicity is peripheral neuropathy (PN) that affects up to 35% of the patients (Richardson et al JCO 2006). We retrospectively reviewed the incidence and severity of PN in 78 patients who received bortezomib at our institution. The median age was 57 years (range: 33–80), 62% were men, and 37% were African Americans (AA). Risk factors for PN included prior use of thalidomide in 53 patients (68%) and vincristine in 31 patients (40%). Seventeen patients (22%) had diabetes mellitus. Before bortezomib treatment 29 patients (37%) reported subjective grade 1–2 PN. Patients received bortezomib alone (n=10) or in combination with dexamethasone (n=36) and thalidomide (n=20) or chemotherapy (n=12). Responses included complete, near complete and partial responses in 5%, 10% and 27%, respectively. Grade 2 and higher PN occurred in 52% of the patients including Grade grades 3 and 4 PN in 15% and 7%, respectively. Twelve patients stopped bortezomib due to side effects that included PN (n=8), diarrhea (n=2) and CMV pneumonia (n=1), and 11 patients had dose reductions because of PN and fatigue. Grade 4 PN affected 6 patients (sensory n=4, and motor/sensory, n=2), 5 of whom were AA and 4 of whom had DM. The onset of grade 4 PN was acute rather than cumulative as noted with lower grades and took a median of 8 months (range: 4–16+) to improve compared to 3–4 months for lower grade PN. Neuropathy grade was not associated with age, sex, race or renal function (10 patients had creatinine > 2 mg/dl, including 2 on dialysis). Factors predictive of PN were baseline neuropathy (p=0.002) in addition to prior thalidomide use (p=0.03) and presence of DM (p=0.03). Responses were independent of neuropathy grade and whether bortezomib was combined with chemotherapy or thalidomide. The duration of therapy in responding patients was longer in patients receiving bortezomib in combination with thalidomide with a median of 5 cycles (range: 2–36) versus those who received other bortezomib combinations 3 cycles (range 1–19). Two of four patients with grade 4 sensory PN had their best response ever after 3 cycles of bortezomib; both had failed transplant and thalidomide based therapies; one remains in continuous complete remission for 24 months. PN therapy was mostly supportive including combinations of analgesics duloxetine, gabapentin, and pregabalin. Interestingly, 6 of 9 patients with PN who received lenalidomide as salvage therapy after progression on bortezomib had significant improvement in their symptoms; 3 of them stopped analgesics. In conclusion, the highest risk and grade of bortezomib neurotoxicity was seen in patients with baseline PN secondary to prior thalidomide use and DM. On the other hand, responding patients who received bortezomib in combination with thalidomide remained longer on therapy with minimal dose reductions. Although this may represent a section bias it is possible that thalidomide's known anti-inflammatory and anti-angiogenesis properties protect against bortezomib-induced PN. Similar effects may explain the unexpected symptomatic improvement of PN on lenalidomide.

An experimental model of peripheral neuropathy induced in rats by Karwinskia humboldtiana (buckthorn) fruit

Intoxication by Karwinskia humboldtiana (buckthorn) fruit presents a neurological picture similar to that of Guillain-Barré syndrome. In this report, we describe an experimental animal model of peripheral neuropathy induced by buckthorn fruit. Four groups of Wistar rats received one oral dose of 1.5 g/kg followed by oral doses of 0.5 g/kg at days 3, 7, 10, and 14 of dried and ground buckthorn fruit in aqueous suspension. Rats were sacrificed at 24, 48, 58, and 112 days after initial dose. Treated animals developed progressive paralysis through 58 days, then completely recovered by 112 days. Sciatic nerves showed segmental demyelination and cellular infiltrates until 58 days after exposure and then remyelinating changes at 112 days. This experimental model for peripheral neuropathy is reproducible and easy to handle. Its manipulation is relatively innocuous and allows us to study reversible peripheral nerve damage. This model can be developed in other animal species and may be useful to test new therapies for peripheral neuropathy.

Effectiveness of Monochromatic Infrared Photo Energy and Physical Therapy for Peripheral Neuropathy: Changes in Sensation, Pain, and Balance-A Preliminary, Multi-Center Study

Effectiveness of Monochromatic Infrared Photo Energy and Physical Therapy for Peripheral Neuropathy: Changes in Sensation, Pain, and Balance-A Preliminary, Multi-Center Study

Effectiveness of Monochromatic Infrared Photo Energy and Physical Therapy for Peripheral Neuropathy: Changes in Sensation, Pain, and Balance–A Preliminary, Multi-Center Study

Objective: To evaluate the effect of monochromatic infrared photo energy (MIRE™) combined with physical therapy in reducing pain, improving sensation, and increasing balance in patients with peripheral neuropathy.Methods: Pain [VAS scale], diminished foot sensation [Semmes Weinstein Monofilament 5.07], and balance deficits [Tinetti Assessment Tool] of 272 patients, average age 69 years, were documented before and after receiving treatments at eight physical therapy clinics.Results: Neuropathic pain, diminished foot sensation, and balance impairments at baseline were present in 93% of patients. After an average of 18 treatments, neuropathic pain decreased by 38%, lower extremity sensory impairment improved by 77%, and balance deficits decreased by 73% [P ≤ 0.006 for all results].Conclusions: Compared with the literature, preliminary findings suggest that MIRE™ plus manual physical therapy improves pain, balance, and sensation symptoms in patients with peripheral neuropathy, at least temporarily.

Intravenous Immunoglobulin in Therapy of Peripheral Neuropathy

Peripheral neuropathy (PN) can be a manifestation of various neurological, infectious, metabolic, autoimmune, rheumatic, and malignant diseases. During the past decade, intravenous immunoglobulin (IVIg) has been increasingly used in the therapy of PN. Compared with other immunomodulatory therapies, IVIg has an excellent safety profile. IVIg is used today as a first-line therapy in the treatment of Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy. Some small studies and reports of clinical cases presented in this article found benefit from IVIg in treating PN associated with diabetes, paraproteinemia, HIV, multisystem rheumatic diseases, and paraneoplastic PN. No clear recommendations can be made relating the use of IVIg in these conditions. Prospective, randomized trials are required to clarify this issue.

Monochromatic Infrared Photo Energy and Physical Therapy for Peripheral Neuropathy: Influence on Sensation, Balance, and Falls

Monochromatic Infrared Photo Energy and Physical Therapy for Peripheral Neuropathy: Influence on Sensation, Balance, and Falls