Association of vitamin D deficiency and subclinical diabetic peripheral neuropathy in type 2 diabetes patients.

Background: Diabetic peripheral neuropathy (DPN) contributes to disability and imposes heavy burdens, while subclinical DPN is lack of attention so far. We aimed to investigate the relationship between vitamin D and distinct subtypes of subclinical DPN in type 2 diabetes (T2DM) patients. Methods: This cross-sectional study included 3629 T2DM inpatients who undertook nerve conduction study to detect subclinical DPN in Zhongshan Hospital between March 2012 and December 2019. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25(OH)D) level < 50 nmol/L. Results: 1620 (44.6%) patients had subclinical DPN and they were further divided into subgroups: distal symmetric polyneuropathy (DSPN) (n=685), mononeuropathy (n=679) and radiculopathy (n=256). Compared with non-DPN, DPN group had significantly lower level of 25(OH)D (P < 0.05). In DPN subtypes, only DSPN patients had significantly lower levels of 25(OH)D (36.18 ± 19.47 vs. 41.03 ± 18.47 nmol/L, P < 0.001) and higher proportion of vitamin D deficiency (78.54% vs. 72.18%, P < 0.001) than non-DPN. Vitamin D deficiency was associated with the increased prevalence of subclinical DPN [odds ratio (OR) 1.276, 95% confidence interval (CI) 1.086-1.501, P = 0.003] and DSPN [OR 1. 646, 95% CI 1.31-2.078, P < 0.001], independent of sex, age, weight, blood pressure, glycosylated hemoglobin, T2DM duration, calcium, phosphorus, parathyroid hormone, lipids and renal function. The association between vitamin D deficiency and mononeuropathy or radiculopathy was not statistically significant. A negative linear association was observed between 25(OH)D and subclinical DSPN. Vitamin D deficiency maintained its significant association with subclinical DSPN in all age groups. Conclusions: Vitamin D deficiency was independently associated with subclinical DSPN, rather than other DPN subtypes.

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.

Painless progressive mononeuritis multiplex secondary to AML associated neuroleukemiosis.

Neuroleukemiosis describes peripheral nerve involvement secondary to leukemic infiltration, a rare complication of leukemia with various clinical presentations, leading to diagnostic challenges for hematologists and neurologists. We present two cases of painless progressive mononeuritis multiplex secondary to neuroleukemiosis. A literature review of previously reported cases of neuroleukemiosis was undertaken. Neuroleukemiosis may present as a progressive mononeuritis multiplex. The diagnosis of neuroleukemiosis requires a high index of suspicion and be aided by repeated CSF analysis.

Characteristics of Peripheral Neuropathy in Patients With Livedoid Vasculopathy.

ABSTRACT: Livedoid vasculopathy (LV) is an ulcerative disorder of the lower extremities characterized by dermal vessel thrombosis with unclear cause. Recent reports of LV-associated upper extremity peripheral neuropathy and epineurial thrombosis suggest a systemic etiology for the condition. We sought to outline the characteristics of peripheral neuropathy in patients with LV. Cases of LV with concurrent peripheral neuropathy and reviewable electrodiagnostic testing reports were identified by electronic medical record database query and examined in detail. Of 53 patients with LV, 33 (62%) had peripheral neuropathy, 11 had reviewable electrodiagnostic reports, and 6 had no clear alternative explanation for neuropathy. Distal symmetric polyneuropathy was the most commonly observed pattern of neuropathy (n = 3) followed by mononeuropathy multiplex (n = 2). Most patients experienced symptoms in both upper and lower extremities (n = 4). Peripheral neuropathy is common in patients with LV. Whether this association is reflective of a systemic, prothrombotic etiology remains to be determined.

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 Case of Eosinophilic Granulomatosis with Polyangiitis Presenting with Mononeuritis Multiplex.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg Strauss syndrome, is an uncommon vasculitis associated with antineutrophil cytoplasmic antibody (ANCA). The hallmarks of the disease are asthma, eosinophilia, and systemic vasculitis with varying degrees of neurological, cutaneous, cardiac, gastrointestinal, and renal involvement. Diagnosis is often difficult since the symptoms are diverse, and a number of differentials need to be excluded. CASE PRESENTATION: In this report, we describe a 60-year-old patient who presented with mononeuritis multiplex and a painful skin rash. A history of late-onset asthma, which was poorly controlled, led us to suspect EGPA. Laboratory data showed leukocytosis, eosinophilia (>10%), elevated ESR, CRP, and IgE, normal chest Xray, positive rheumatoid factor (RA), perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA), and evidence of extravascular eosinophils in histopathology report of skin biopsy. She was treated with methylprednisolone and cyclophosphamide pulse therapy with a satisfactory response. CONCLUSION: Diagnosis of EGPA requires a combination of clinical and histopathological findings to meet the diagnostic criteria. A history of poorly controlled or late-onset asthma may guide us to the diagnosis that is frequently overlooked. Due to the wide heterogeneity of EGPA patients' phenotypes, sharp, professional judgment is needed for early disease detection and treatment in order to avoid irreversible changes and poor outcomes.

Progressive Multiple Mononeuropathy in a Patient With Familial Transthyretin Amyloidosis After Liver Transplantation.

ABSTRACT: Valine 122 isoleucine (V122I) is the most common mutation associated with familial transthyretin-related amyloidosis (fATTR) in the metropolitan United States. V122I-related fATTR usually presents with cardiomyopathy. When polyneuropathy is encountered, it is usually mild, distal, and axonal in nature. Although liver transplantation improves survival for fATTR neuropathy patients, neuropathy may progress post liver transplantation because of the deposition of wild-type transthyretin. We report a patient with homozygous V122I mutation who presented with asymmetrical, upper limb predominant neuropathy rather early in his disease course, which progressed for a period of 5 years after liver transplantation before stabilization with the initiation of patisiran.

Peripheral neuropathy and livedoid vasculopathy.

BACKGROUND: Livedoid vasculopathy (LV) is a chronic dermatosis associated with micro-thrombosis of the vessels of the dermis, leading to ischemic lesions and painful skin ulcerations of the lower limbs. This thrombosing occlusive vasculopathy, clearly distinct from 'classical vasculitis' (not related to alteration of vessel walls), may lead to peripheral neuropathy. OBJECTIVE: To clarify the main clinical, electrophysiological and pathological characteristics of peripheral neuropathy linked to LV. METHOD: We presented a series of personal cases of peripheral neuropathy due to LV. We also conducted a review of the literature (since the first description of LV in 1974) using multiple combinations of keywords from 'PubMed', 'Google Scholar' and 'ScienceDirect' databases according to the 'Preferred Reporting Items for Systematic reviews and Meta-Analyses' guidelines. RESULTS: We identified 16 patients (6 personal cases and 10 cases from the medical literature). Our personal cases were five females and one male, with a median age (at the onset of cutaneous signs of LV) of 38 (range 25-62). Several types of skin lesions of the lower limbs were observed. Median age at the onset of peripheral neuropathy symptoms was 48 years (range 29-66), with a main clinical and electrophysiological pattern of mononeuropathy multiplex. DISCUSSION: We observed a typical pattern of peripheral neuropathy, mostly mononeuropathy multiplex, whose pathophysiology might be related to occlusions of the small vessels of the nerves, as seen in the dermis. Moreover, LV may also be associated with other types of peripheral neuropathies (sometimes of autoimmune etiology) not directly related to the skin lesions. CONCLUSION: The 'ischemic form' of peripheral neuropathy linked to LV is mainly responsible for sensory disturbances (with multifocal distribution), sometimes for motor disturbances. This type of peripheral neuropathy has to be distinguished from 'classical vasculitic neuropathies' which are usually treated with antithrombotic therapies.

Childhood focal compressive mononeuropathies during the COVID-19 pandemic in Buenos Aires, Argentina.

INTRODUCTION/AIMS: Focal peripheral neuropathies are infrequently seen in pediatric patients. The COVID-19 pandemic has disrupted normal life for many people, including complete lockdowns and school closing for long periods of time in many countries, which prompted children to stay at home. Our aim is to assess whether there has been an increased incidence of focal compressive peripheral neuropathies in the pediatric population during COVID-19-associated lockdown. METHODS: Clinical, electrophysiological, and imaging characteristics were reviewed for patients referred to the electrodiagnostic (EDx) laboratory with suspicion of a focal neuropathy. The incidence of focal compressive peripheral neuropathies seen during the period of March to September 2020 was compared with the same time period in 2019. RESULTS: An increased incidence of focal neuropathies was seen in 2020 (31%) compared with 2019 (6.8%). During 2020, 7 fibular (peroneal) mononeuropathies and 2 ulnar neuropathies were diagnosed. Most patients with focal neuropathies were underweight and acknowledged prolonged screen time periods. Electrophysiological findings consisted of mostly demyelinating lesions with an overall good clinical outcome. DISCUSSION: In this study we raise awareness about a possible increased incidence of focal compressive peripheral neuropathies in children during COVID-19-associated lockdown, which may be prevented with changing positions during sedentary activities.

Multiple demyelinating sensory and motor mononeuropathy associated with COVID-19: a case report.

The involvement of the nervous system may occur in 36.4% of patients with COVID-19. Cases have been described of cerebrovascular diseases, encephalitis, encephalopathies, and changes in smell and taste. Two months after being discharged from hospital with COVID-19, a 63-year-old male patient presented with a predominantly demyelinating multiple sensory and motor mononeuropathy. A diagnostic possibility of multiple sensory and motor demyelinating mononeuropathy (Lewis-Sumner syndrome) was made. Treatment with human immunoglobulin was initiated. COVID-19 may be associated with multiple demyelinating sensory and motor mononeuropathy.

Bilateral subcutaneous pyelovesical bypass in a Hautmann neobladder followed by a mononeuropathy multiplex and an underlying polyarteritis nodosa diagnosis.

Subcutaneous pyelovesical bypasses are the best choice for the long-term palliative treatment of ureteral obstructions. In rare cases this obstruction is due to polyarteritis nodosa. We present the only reported patient with a bilateral Detour bypass in a Hautmann's neobladder. The patient also suffers from polyarteritis nodosa.

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 Vasculitic Neuropathy Associated With Minocycline Use.

We describe 2 patients presenting with multiplex mononeuritis, associated with skin manifestation, secondary to minocycline-induced vasculitis. One of the cases is associated neither with lupus nor polyarteritis nodosa. An extensive laboratory workup ruled out any possible underlying immunologic disorder. Electrodiagnostic studies were conducted to show axonal neuropathy in patchy and multifocal distribution consistent with multiplex mononeuritis. This diagnosis was confirmed with nerve biopsy. Withdrawing from the offending medication, minocycline, improved the patients' clinical condition and the quantitative serological measures.

Randomized double blind trial of amitriptyline versus placebo in treatment of chronic laryngopharyngeal neuropathy.

OBJECTIVE: A neuropathic etiology has been suggested for patients with chronic laryngopharyngitis symptoms without visible structural pathology. Prior studies have shown that treatment with neuro-modulating medications is beneficial, but it is unknown if this was due to placebo effect. Our objective was to compare the efficacy of amitriptyline versus placebo in treating chronic laryngopharyngeal neuropathy. STUDY DESIGN: Prospective, randomized placebo-controlled trial. METHODS: Patients were randomized to receive placebo or amitriptyline for 8weeks. Primary outcome was change in modified Reflux Symptom Index (mRSI) score. Secondary outcomes were change in Voice Handicap Index-10 (VHI) scores, rates of adverse effects, and overall symptom severity. RESULTS: Eighteen patients completed the study. The average difference in mRSI and VHI-10 scores after treatment were not significantly different between study arms. However, more subjects taking amitriptyline felt their symptoms had subjectively improved (6 out of 9, 67%), while the remainder noted no change. In the placebo group, only 4 out of 9 subjects (44%) felt their symptoms were better and 2 felt worse. Subjects took an average of 25mg of amitriptyline or placebo daily by the end of the 8-week treatment period. No serious adverse effects were noted. CONCLUSION: Although there was a trend toward greater subjective improvement in overall symptoms with amitriptyline, interpretation is limited due to the small sample size. Larger randomized controlled trials to determine the efficacy of neuro-modulating agents in the treatment of chronic laryngopharyngeal neuropathy, as well as better metrics to characterize this disorder, are warranted.

Clinicopathological features of multiple mononeuropathy associated with systemic lupus erythematosus: a multicenter study.

Multiple mononeuropathy (MM) occurs rarely during systemic lupus erythematosus (SLE) but may lead to major disability. The aim of this study was to investigate the clinic-pathological presentations of MM during SLE, as well as long-term outcomes. We conducted a multicentric retrospective study that included patients receiving a diagnosis of MM during SLE. Ten patients were included (8 women and 2 men, median age at MM diagnosis: 40.4 years). SLE was diagnosed before MM in 9/10 patients (median time 8.2 years). When MM occurred, the SLEDAI score was ≥6 for 6/9 patients. Presenting symptoms consisted of sensory deficits (n = 10), neuropathic pain (n = 9), and/or motor deficits (n = 9), sometimes symmetrical, affecting the lower limbs (10/10) and occasionally the upper limbs (5/10). All patients presented with uni- or bilateral damage of the common fibular nerve, with less frequent involvement of the tibial nerve. Serum cryoglobulinemia was positive in 5/9 patients. Electrophysiological studies confirmed the non-symmetrical involvement of multiple nerve trunks in all patients. Neuromuscular biopsy (performed in five patients) showed histological signs of vasculitis in two patients and perivascular lymphocytic inflammatory infiltrates in two others. All patients were treated with glucocorticosteroids combined with cyclophosphamide (n = 6), rituximab (n = 3), or mycophénolate-mofétil (n = 1). The median follow-up was 5 years. Two patients relapsed during follow-up. All patients had motor and/or sensory sequelae upon follow-up. MM associated with SLE is frequently caused by a vasculitis mechanism. Patients improve with steroids and immunosuppressive drugs. Long-term outcomes include frequent clinical sequelae and possible relapses.

Acute Motor-dominant Polyneuropathy as Guillain-Barré Syndrome and Multiple Mononeuropathies in a Patient with Sjögren's Syndrome.

A patient with xerostomia and xerophthalmia due to Sjögren's syndrome presented with acute motor-dominant polyneuropathy and multiple mononeuropathy with antiganglioside antibodies. Nerve conduction studies and a sural nerve biopsy revealed the neuropathy as a mixture of segmental demyelination and axonal degeneration. Positive results were obtained for several antiganglioside antibodies. Corticosteroid treatment proved effective. The neuropathy was considered to represent a mixture of polyneuropathy as Guillain-Barré syndrome and multiple mononeuropathy via Sjögren's syndrome. We speculate that Guillain-Barré syndrome occurred in the patient and Guillain-Barré syndrome itself activated multiple mononeuropathy via Sjögren's syndrome.

Simultaneous acute shoulder arthritis and multiple mononeuropathy in a newly diagnosed type 2 diabetes patient - First case report.

Diabetes is a common disorder that leads to the musculoskeletal symptoms such as the shoulder arthritis. The involvement of peripheral nervous system is one of the troublesome for the patients as it provokes chronic sensory symptoms, lower motor neuron involvement and autonomic symptoms. In the course of the disease there has been several types of neuropathies described. A 41-year-old male patient was admitted to the internal medicine department because of the general weakness, malaise, polydypsia and polyuria since several days. The initial blood glucose level was 780mg/dl. During the first day the continuous insulin infusion was administered. On the next day when he woke up, the severe pain in the right shoulder with limited movement, right upper extremity weakness and burning pain in the radial aspect of this extremity appeared. On examination right shoulder joint movement limitation was found with the muscle weakness and sensory symptoms in the upper limbs. The clinical picture indicated on the right shoulder arthritis and the peripheral nervous system symptoms such as the right musculocutaneous, supraspinatus, right radial nerve and left radial nerve damage. We present a first case report of simultaneous, acute involvement of the shoulder joint and multiple neuropathy in a patient with newly diagnosed type 2 diabetes, presumably in the state of ketoacidosis.

Transcriptional expression of inflammatory mediators in various somatosensory relay centers in the brain of rat models of peripheral mononeuropathy and local inflammation.

Contradictory results have been reported regarding the role of inflammatory mediators in the central nervous system in mediating neuropathic pain and inflammatory hyperalgesia following peripheral nerve injury or localized inflammation. The present study aims to correlate between the mRNA expression and protein secretion of proinflammatory cytokines and nerve growth factor (NGF), in the dorsal root ganglia (DRGs), spinal cord, brainstem and thalamus, and pain-related behavior in animal models of peripheral mononeuropathy and localized inflammation. Different groups of rats (n=8, each) were subjected to either lesion of the nerves of their hindpaws to induce mononeuropathy or intraplantar injection of endotoxin (ET) and were sacrificed at various time intervals. TNF-α, IL-1ß and NGF mRNA expression and protein levels in the various centers involved in processing nociceptive information were determined, by RT-PCR and ELISA. Control groups were either subjected to sham surgery or to saline injection. Mononeuropathy and ET injection produced significant and sustained increases in the mRNA expression and protein levels of TNF-α, IL-1ß and NGF in the ipsilateral and contralateral DRGs, spinal cord, and brainstem. No significant and consistent changes in the mRNA expression of cytokines were noticed in the thalamus, while a downregulation of the NGF-mRNA level was observed. The temporal and spatial patterns of the observed changes in mRNA expression of cytokines and NGF are not closely in phase with the observed allodynia and hyperalgesia in the different models, suggesting that the role of these mediators may not be reduced exclusively to the production and maintenance of pain.

IgG4-Related Sialoadenitis with a Skin Lesion and Multiple Mononeuropathies Suggesting Coexistent Cryoglobulinemic Vasculitis.

A 68-year-old man was admitted because of weakness of the left leg, dysesthesiae of the extremities and bilateral lower extremity purpura. A neurological examination showed mononeuritis multiplex with laboratory evidence of hypocomplementemia, cryoglobulinemia and leukocytoclastic vasculitis in the biopsy of a skin specimen. The patient also exhibited bilateral submandibular gland swelling, elevated serum IgG4 levels and infiltration of a large number of IgG4-positive plasma cells in the submandibular glands. These findings were consistent with both cryoglobulinemic vasculitis and IgG4-related disease. The administration of oral prednisolone (1 mg/kg/day) resolved the neurological manifestations and the swelling of the submandibular glands and cryoglobulinemia.