Ramen noodle neuropathy: an atypical case of partial paralysis from malnutrition.

INTRODUCTION: Due to a COVID-related job loss resulting in financial and food insecurity, a 28-year-old woman initiated a diet consisting solely of one cup of ramen noodles daily for twenty-two months, leading to 27 kg of weight loss. Ramen noodles are low in calories and lack key nutrients, including potassium, chloride, and vitamin B12. CASE DESCRIPTION: The patient presented to the emergency department with acute, worsening weakness and paresthesias in her left wrist and hand. Exam revealed no other abnormalities aside from a cachectic appearance. Labs revealed marked hypokalemia, hypochloremia, lactic acidosis, a mixed metabolic alkalosis with respiratory acidosis, and low levels of zinc and copper. An EKG revealed a prolonged QT interval. After a neurology and psychiatry consult, the patient was admitted for failure to thrive with malnutrition, peripheral neuropathy, hypokalemia, and an acid-base disorder. An MRI of the brain was unremarkable. Studies of other nutritional deficiencies, autoimmune conditions, and sexually transmitted infections were unremarkable. The patient received food and vitamin supplementation, was monitored for re-feeding syndrome, and had a significant recovery. DISCUSSION: After stroke, spinal injury, multiple sclerosis, and the most common focal mononeuropathies were ruled out, the clinical focus turned to nutritional deficiencies, the most significant of which was hypokalemia. Prior research has shown that severe hypokalemia can lead to weakness. It has also shown that chronically insufficient dietary intake is a common cause of hypokalemia. This case, with its partial paralysis of a unilateral upper extremity, may add to the known clinical manifestations of hypokalemia. We review the role of hypokalemia and hypochloremia in acid-base dynamics. Etiologies and clinical manifestations of cobalamin, thiamine, pyridoxine, and copper deficiencies, along with lead toxicity, are also discussed. Diagnostic clarity of mononeuropathies in the context of malnutrition and hypokalemia can be aided by urine potassium levels prior to repletion, neuroimaging that includes the cervical spine, and follow-up electromyography.

A 17-year-old boy who presented with acute mononeuropathy was found to have Type 1 diabetes.

Diabetic neuropathy in children and adolescents with Type 1 diabetes mellitus is rare and is usually subclinical and a complication of the late diabetes period. A 17-year-old boy admitted with a right foot drop of sudden onset was diagnosed with peroneal nerve palsy. He had had osmotic polyuria, polydipsia and weight loss for the past 2 months; his blood glucose was 25 mmol/L (<7.8), HbA1c 15.2% (4.0-5.6) and vitamin B12 125 pg/ml (180-914). The peroneal nerve palsy resolved within 3 months with blood glucose regulation and B12 supplementation. Diabetes should be borne in mind in the differential diagnosis of unusual cases of mononeuropathy.Abbreviations: DCCTS: Diabetes Control and Complications Trial Study; DM: diabetes mellitus; DN: diabetic neuropathy; GAD: glutamic acid decarboxylase; PN: peripheral neuropathy; T1DM: Type 1 diabetes mellitus.

A review of the StimRouter® peripheral neuromodulation system for chronic pain management.

The StimRouter® peripheral nerve stimulation system created by Bioness, Inc., (CA, USA) is US FDA-approved for the treatment of peripheral mononeuropathy refractory to conservative medical management. StimRouter is a minimally invasive system that utilizes a subcutaneously implanted lead with integrated anchor and electrodes, and an external pulse generator to produce peripheral neuromodulation and achieve pain relief. Multiple published clinical trials reviewed here have shown the StimRouter system to have a high margin of safety, differentiating it from other existing peripheral neuromodulation systems requiring open surgical electrode placement and implantable pulse generators. These studies have also shown the StimRouter system to be efficacious in the treatment of multiple peripheral mononeuropathies; improving patient pain, activity levels and quality of life. StimRouter represents a feasible option for management of chronic peripheral mononeuropathy.

Prospective case series on the use of peripheral nerve stimulation for focal mononeuropathy treatment.

Aim: This case series looks at outcomes in 39 patients implanted using the Bioness Stimrouter system on various isolated mononeuropathies. Patients & methods: A case series of 39 patients with a total of 42 implants were enrolled starting August 2017 at various pain management centers. Results: Of 39 patients studied, 78% of the participants noticed an improvement in their pain. There was a 71% reduction in pain scores with the average preprocedure score of 8 improving to 2 post-implant. Participants noted on average a 72% improvement in activity with the greatest observed in the brachial plexus (80%) and suprascapular nerve (80%) and smallest in the intercostal nerve (40%). Approximately 89% of those implanted with a peripheral nerve stimulator experienced a greater than 50% reduction in opioid consumption. Conclusion: Peripheral nerve stimulators are a new, minimally invasive neuromodulation modality that shows promising early results in our 39-patient case series.

Peripheral Nerve Stimulation for Painful Mononeuropathy Secondary to Leprosy: A 12-Month Follow-Up Study.

OBJECTIVE: Leprosy affects approximately 10-15 million patients worldwide and remains a relevant public health issue. Chronic pain secondary to leprosy is a primary cause of morbidity, and its treatment remains a challenge. We evaluated the feasibility and safety of peripheral nerve stimulation (PNS) for painful mononeuropathy secondary to leprosy that is refractory to pharmacological therapy and surgical intervention (decompression). METHODS: Between 2011 and 2013 twenty-three patients with painful mononeuropathy secondary to leprosy were recruited to this prospective case series. All patients were considered to be refractory to optimized conservative treatment and neurosurgical decompression. Pain was evaluated over the course of the study using the neuropathic pain scale and the visual analog scale for pain. In the first stage, patients were implanted with a temporary electrode that was connected to an external stimulator, and were treated with PNS for seven days. Patients with 50% or greater pain relief received a definitive implantation in the second stage. Follow-ups in the second stage were conducted at 1, 3, 6, and 12 months. RESULTS: After seven days of trial in the first stage, 10 patients showed a pain reduction of 50% or greater. At 12-month follow-up in the second stage, 6 of the 10 patients who underwent permanent device implantation showed a pain reduction of 50% or greater (75% reduction on average), and two patients showed a 30% reduction in pain. Two patients presented with electrode migration that required repositioning during the 12-month follow-up period. CONCLUSIONS: Our data suggest that PNS might have significant long-term utility for the treatment of painful mononeuropathy secondary to leprosy. Future studies should be performed in order to corroborate our findings in a larger population and encourage the clinical implementation of this technique.

Chronic curcumin treatment normalizes depression-like behaviors in mice with mononeuropathy: involvement of supraspinal serotonergic system and GABAA receptor.

RATIONALE: Comorbid depression is commonly observed in individuals who suffer from neuropathic pain, which necessitates improved treatment. Curcumin, a phenolic compound derived from Curcuma longa, possesses both antinociceptive and antidepressant-like activities in animal studies, suggesting its possible usefulness in treating this comorbidity. OBJECTIVE: We investigated the effect of curcumin on depressive-like behaviors in mice with mononeuropathy, and explored the mechanism(s). METHODS: Chronic constriction injury (CCI) was produced by loosely ligating the sciatic nerves in mice. The nociceptive behaviors were examined using Hargreaves test, and the depressive-like behaviors were determined by forced swim test (FST) and tail suspension test (TST). RESULTS: After CCI injury, the neuropathic mice developed nociceptive and depressive-like behaviors, as shown by thermal hyperalgesia in Hargreaves test and protracted immobility time in FST and TST. Chronic treatment of neuropathic mice with curcumin (45 mg/kg, p.o., twice per day for 3 weeks) corrected their exacerbated nociceptive and depressive-like behaviors, which was abolished by chemical depletion of brain serotonin rather than noradrenaline. The paralleled antinociceptive and antidepressant-like actions of curcumin seem to be pharmacologically segregated, since intrathecal and intracerebroventricular injection of methysergide, a nonselective 5-HT receptor antagonist, separately counteracted the two actions of curcumin. Further, this antidepression was abrogated by repeated co-treatment with 5-HT1A receptor antagonist WAY-100635 and greatly attenuated by acute co-treatment with GABAA receptor antagonist bicuculline. CONCLUSION: Curcumin can normalize the depressive-like behaviors of neuropathic mice, which may be independent of the concurrent analgesic action and possibly mediated via the supraspinal serotonergic system and downstream GABAA receptor.

[Effects of lycium barbarum polysaccharide on formation of traumatic neuroma and pain after transection of sciatic nerve in rats].

OBJECTIVE: To investigate the effects of lycium barbarum polysaccharide (LBP) on the formation of traumatic neuroma and pain after transection of sciatic nerve in rats. METHODS: Forty Sprague-Dawley (SD) rats, weighing 200-220 g, half male and half female, were allocated into 2 groups randomly: LBP group and control group (n = 20 per group). The right sciatic nerves were transected and 2 cm sciatic nerve were removed in all rats of the 2 groups. LBP were intraperitoneally injected in a volume of 10 mg/(kgd) in the LBP group, while the same volume normal saline (NS) in the control group for 28 days. The deficiency of toenail and toe were observed to estimate the autophagy of the operated limb. Light microscope and transmission electron microscope were used to observe the formation of traumatic neuroma after transection of sciatic nerve. RESULTS: Autophagy was observed in 5 rats (25%) of LBP group and in 12 rats (60%) of control group at 4 weeks, showing significant difference (P < 0.05). Neuroma formed in 8 rats (40%) of LBP group and in 16 rats (80%) of control group, showing significant difference (P < 0.05). The observation of light microscope showed that there were unorganized growth cells in the neuroma, infiltrated muscle cells, the regeneration of axons and ensheathing cells to form small patch and funicular structure in the control group, while in the LBP group there were less proliferation of nerve fibers with a regular arrangement. Transmission electron microscope showed that there were lots of axons in nerve tumour, more fusoid fibroblasts, more collagen fiber, and hyperplasia and degenerated myelin sheath in the control group, while in the LBP group there were less myelin sheath in the proximal end of injuring nerves, less Schwann cells and fibroblasts, and sparsed collagen fibers. CONCLUSION: LBP can inhibit autophagy and the formation of traumatic neuroma after transection of sciatic nerve in rats.

All-trans retinoic acid-induced focal myositis, synovitis, and mononeuritis.

All-trans retinoic acid has revolutionized the treatment of acute promyelocytic leukemia, but this therapy is often complicated by the all-trans retinoic acid syndrome. Here we report a patient with newly diagnosed acute promyelocytic leukemia who developed acute focal myositis, synovitis, and possible vasculitis, after receiving all-trans retinoic acid therapy. We review the existing literature on this rare clinical entity, all-trans retinoic acid-induced myositis. This condition can manifest as fever, myalgia, arthralgia, and Sweet syndrome, accompanied by distinct magnetic resonance findings involving the lower extremity musculature. Treatment consists of discontinuation of the offending drug and often high dose corticosteroids.

Activity of new NOP receptor ligands in a rat peripheral mononeuropathy model: potentiation of morphine anti-allodynic activity by NOP receptor antagonists.

The effect of new NOP receptor agonists and antagonists in the rat chronic constriction injury model was investigated. Intraperitoneally administered NOP receptor agonist SR14150 and antagonists SR16430 and SR14148, had no effect on mechanical allodynia when given alone. The nonselective NOP/mu-opioid receptor agonist SR16435, however, produced an anti-allodynic response, similar to morphine and reversible by naloxone. Notably, co-administration of the NOP receptor antagonists potentiated the anti-allodynic activity of both morphine and SR16435. Increased levels of the NOP receptor are implicated in the reduced efficacy of morphine in neuropathic pain. Our results suggest the utility of NOP receptor antagonists for potentiating opioid efficacy in chronic pain.

Omalgia pruriginosa / Pruriginous omodynia

La notalgia parestésica es una mononeuropatía sensitiva producida por atrapamiento de los ramos dorsales de las raíces espinales de D2 a D6, debido a que estos nervios se angulan 90° al pasar por la musculatura paraespinal. Se desconoce su causa, pero se ha visto relacionada con alteraciones en la estática de la columna a ese nivel (artrosis, escoliosis). Parestesias, prurito y quemazón son los síntomas más frecuentes y, junto con el hallazgo de una placa hiperpigmentada en dicha localización, constituyen los pilares de su diagnóstico. La electroneurografía muestra signos de denervación en las raíces afectadas. Únicamente la capsaicina tópica ha demostrado eficacia en ensayos clínicos. Otras terapias descritas en la literatura son la acupuntura, el bloqueo anestésico paravertebral local, la fisioterapia y la oxcarbazepina (AU)

Notalgia paresthetica is a sensory mononeuropathy producedby the dorsal spinal nerve root branch entrapmentfrom D2 to D6 because these nerves are angles 90° when passingthrough the paraspinal musculature. Its cause is unknownbut it has been observed to be related with alterationsin the spinal cord statics at this level (arthritis, scoliosis). Paresthesias,pruritus and burning sensation are the most frequentsymptoms. Together with the finding of a hyperpigmentedplaque at that location, they are the mainstay of itsdiagnosis. The electroneurography shows signs of denervationin the affected roots. Only topical capsaicin has beenshown to be effective in clinical trials. Other therapies describedin the literature are acupunture, local paravertebralblock anesthesia, physical therapy and oxcarbazepine (AU)

Muscarinic receptor activation potentiates the effect of spinal cord stimulation on pain-related behavior in rats with mononeuropathy.

Spinal cord stimulation (SCS) has proven to be a valuable treatment in neuropathic pain. Our previous animal experiments performed on rat models of SCS and ensuing clinical trials have demonstrated that intrathecal (i.t.) administration of subeffective doses of certain drugs may enhance the pain relieving effect of SCS in cases with unsatisfactory SCS outcome. Recently, an augmented release of spinal acetylcholine acting on muscarinic receptors has been shown to be one of the mechanisms involved in SCS. The present study was performed to examine whether cold hypersensitivity and heat hyperalgesia in rats with partial sciatic nerve injuries can be attenuated by SCS in the same way as tactile hypersensitivity and to explore a possibly synergistic effect of SCS and a muscarinic receptor agonist, oxotremorine. Rats with signs of neuropathy were subjected to SCS applied in awake, freely moving condition. Oxotremorine was administered intrathecally. Tactile, cold and heat sensitivities were assessed by using von Frey filaments, cold spray and focused radiant heat, respectively. Oxotremorine i.t. dose-dependently suppressed the tactile hypersensitivity. SCS markedly increased withdrawal thresholds (WTs), withdrawal latencies and cold scores. When combining SCS with a subeffective dose of oxotremorine i.t., the suppressive effect of SCS on the pain-related symptoms was dramatically enhanced in rats failing to obtain a satisfactory effect with SCS alone. In conclusion, the combination of SCS and a drug with selective muscarinic receptor agonistic properties could be an optional therapy, when SCS per se has proven inefficient.

A synthetic kainoid, (2S,3R,4R)-3-carboxymethyl-4-(phenylthio)pyrrolidine-2-carboxylic acid (PSPA-1) serves as a novel anti-allodynic agent for neuropathic pain.

In spite of prominent progress in basic pain research, neuropathic pain remains a significant medical problem, because it is often poorly relieved by conventional analgesics. Thus this situation encourages us to make more sophisticated efforts toward the discovery of new analgesics. We previously showed that i.t. administration of acromelic acid-A (ACRO-A), a Japanese mushroom poison, provoked prominent tactile pain (allodynia) at an extremely low dose of 1 fg/mouse. In the present study we synthesized ACRO-A analogues (2S,3R,4R)-3-carboxymethyl-4-phenoxypyrrolidine-2-carboxylic acid (POPA-2) and (2S,3R,4R)-3-carboxymethyl-4-(phenylthio)pyrrolidine-2-carboxylic acid (PSPA-1) chemically and examined their ability to induce allodynia in conscious mice. Whereas POPA-2 induced allodynia at extremely low doses from 1 to 100 fg/mouse, similar to ACRO-A, PSPA-1 did not induce allodynia; rather, it inhibited the ACRO-A-induced allodynia with an ID(50) value (95% confidence limits) of 2.19 fg/mouse (0.04-31.8 fg/mouse). Furthermore, PSPA-1 relieved neuropathic pain produced by L5 spinal nerve transection on day 7 after the operation in a dose-dependent manner from 1 to 100 pg/mouse. In contrast, it did not affect thermal or mechanical nociception or inflammatory pain. PSPA-1 reduced the increase in neuronal nitric oxide synthase activity in the spinal cord of neuropathic pain mice assessed by NADPH-diaphorase histochemistry and blocked the allodynia induced by N-methyl-d-aspartate. These results demonstrate that PSPA-1 may represent a novel class of anti-allodynic agents for neuropathic pain acting by blocking the glutamate-nitric oxide pathway.

Antinociceptive activity of the selective iNOS inhibitor AR-C102222 in rodent models of inflammatory, neuropathic and post-operative pain.

Nitric oxide generated by the nitric oxide synthase (NOS) isoforms contributes to pain processing. The selective inhibition of iNOS might represent a novel, therapeutic target for the development of antinociceptive compounds. However, few isoform-selective inhibitors of NOS have been developed. The present experiments examined the anti-inflammatory and antinociceptive activity of a selective inducible nitric oxide (iNOS) inhibitor, AR-C102222, on arachidonic acid-induced ear inflammation, Freund's complete adjuvant (FCA)-induced hyperalgesia, acetic acid-induced writhing, and tactile allodynia produced by L5 spinal nerve ligation (L5 SNL) or hindpaw incision (INC). AR-C102222 at a dose of 100mg/kg p.o., significantly reduced inflammation produced by the application of arachidonic acid to the ear, attenuated FCA-induced mechanical hyperalgesia, and attenuated acetic acid-induced writhing. In the L5 SNL and INC surgical procedures, tactile allodynia produced by both procedures was significantly reduced by 30mg/kg i.p. of AR-C102222. These data demonstrate that the selective inhibition of iNOS produces antinociception in different models of pain and suggest that the iNOS-NO system plays a role in pain processing.

Paw withdrawal thresholds and persistent hindlimb flexion in experimental mononeuropathies.

Hypersensitivity of the foot produced by a number of sciatic mononeuropathies was assessed and compared. A new tool was used, the strain-gauge algometer, that delivers a noxious stimulus and gives a direct measurement of the force for paw withdrawal. In addition, we report observations of another alteration of the flexion reflex, persistent hindlimb flexion. The mean mechanical threshold for naive rats was 5.9 +/- 0.97 centinewton (standard deviation). A superficial surgical procedure had no effect on mechanical sensitivity. Sham surgeries and a surgery in which a silicone pellet was glued to the sciatic nerve produced moderate increases in mechanical sensitivity. Interventions that produced the greatest reductions in thresholds were carrageenan neuritis, complete Freund's adjuvant neuritis, and the chronic constriction injury (CCI) model. Mechanical thresholds returned to baseline in 2 weeks in all groups. Neuropathic behaviors (licking and holding the paw after the stimulus) were observed more frequently in the CCI group. Persistent hindlimb flexion was only observed in the CCI group. The results support that midaxonal inflammation is sufficient to induce hyperalgesia. The strain-gauge algometer proved to be efficient and reliable, and calculations support that used as described in this report one can demonstrate changes in paw withdrawal thresholds as small as 15%.

Microvasculitic paraproteinaemic polyneuropathy and B-cell lymphoma.

Microvasculitis may play a greater part in the pathogenesis of paraproteinaemic neuropathies than is generally recognised, producing tissue destruction by convergent immune and physical mechanisms. We present a patient with a clinical syndrome of mononeuritis multiplex and a circulating IgM lambda paraprotein, in whom bone marrow aspiration revealed a lymphoplasmacytoid lymphoma. Microvasculitic changes were present in the first nerve biopsy, and the second showed extensive destruction of neural architecture and deposition of IgM-related material. A 2-stage pathogenic cascade is postulated and explored with a review of the relevant literature.

Peripheral and central sites of action for A-85380 in the spinal nerve ligation model of neuropathic pain.

Neuronal nicotinic receptor (NNR) agonists such as ABT 594 have been shown to be effective in a wide range of preclinical models of acute and neuropathic pain. The present study, using the NNR agonist A-85380, sought to determine if NNR agonists are acting via similar or differing mechanisms to induce anti-nociception and anti-allodynia. A systemic administration of the quaternary NNR antagonist chlorisondamine (0.4 micromol/kg, intraperitoneal (i.p.)) did not alter A-85380-induced (0.75 micromol/kg, i.p.) anti-nociception in the rat paw withdrawal model of acute thermal pain. In contrast, previous studies have demonstrated that blockade of central NNRs by prior administration of chlorisondamine (10 microg i.c.v.) prevents A-85380 induced anti-nociception indicating a predominantly central site of action of NNR agonists in relieving acute pain. In the rat spinal nerve ligation model of neuropathic pain, A-85380 induced a dose-dependent anti-allodynia (0.5-1.0 micromol/kg) that was blocked by pretreatment with mecamylamine (1 micromol/kg). Interestingly, unlike acute pain, both systemic and central administration of chlorisondamine blocked A-85380-induced anti-allodynia, an effect that was determined not to be due to a non-specific effect of chlorisondamine or to chlorisondamine crossing the blood-brain barrier. The peripheral site of action was shown not to be the primary receptive field, since A-85380 had equally potent anti-allodynic effects when it was injected into either the affected or unaffected paw. In contrast, infusion of A-85380 directly onto the L5 dorsal root ganglion on the affected side resulted in a dose-dependent and marked anti-allodynia (10-20 microg) at doses that had no effect when injected systemically. This effect was blocked by pretreatment with chlorisondamine. Together these data further support the idea that different mechanisms underlie different pain states and suggest that the effects of NNR agonists in neuropathic pain may be due in part to peripheral actions of the compounds.