Idiopathic membranous nephropathy and synchronous mononeuritis multiplex secondary to idiopathic small vessel vasculitis.

Membranous nephropathy has been associated with demyelinating polyneuropathies and antiglomerular membrane disease; however, an association with vasculitic neuropathy has not been described. This case describes a patient with biopsy-proven idiopathic membranous nephropathy and synchronous mononeuritis multiplex secondary to idiopathic small vessel vasculitis, who presented with lower limb microvascular ischaemia, peripheral neuropathy and active urinary sediment. Her extensive non-invasive screening for immunological disease and radiological investigations for occult malignancy were unremarkable. The patient received intravenous methylprednisolone and intravenous rituximab induction therapy resulting in complete remission of both the idiopathic membranous nephropathy and small vessel vasculitis at 7 months post treatment.

A severe case of neuroleukemiosis caused by B cell chronic lymphocytic leukemia, presenting as mononeuritis multiplex.

AIMS: To report an exceptional case of nerve infiltration by an otherwise benign chronic B cell leukemia, inducing severe mononeuritis multiplex. METHODS: The patient underwent extensive evaluation, including nerve conduction study and myography, brain and plexus MRI, and nerve biopsy. RESULTS: The clinical and electrophysiological diagnosis was a mononeuritis multiplex with severe motor and sensory involvement; only the nerve biopsy allowed definite diagnosis and introduction of chemotherapy, leading to resolution of sensory deficit and progressive motor improvement. DISCUSSION: Neuroleukemiosis caused by chronic lymphoid leukemia is an exceptional diagnosis. The presence of other possible causes like cryoglobulinemia could induce avoidance of nerve biopsy thus undertreating patient, since steroid treatment is not expected to be efficient on lymphocytic proliferation. Our case stretches the importance of nerve biopsy and raises neuromuscular specialist's awareness of this rare entity.

Mononeuritis multiplex as a rare and severe neurological complication of immune checkpoint inhibitors: a case report.

BACKGROUND: Mononeuritis multiplex is a rare autoimmune peripheral neuropathy that typically presents in the context of vasculitis, diabetes, infection, or as a paraneoplastic syndrome. Adverse immune-related neurological conditions have been increasingly reported with the use of immune checkpoint inhibitors against cytotoxic T-lymphocyte antigen-4 and/or the programmed cell death protein 1/programmed death ligand-1 axis. Mononeuritis multiplex has only been reported twice from treatment of cancers with immunotherapy. CASE PRESENTATION: Here we report a case of mononeuritis multiplex as a complication of immune checkpoint inhibitor therapy for melanoma. An 80-year-old non-Hispanic white female with recurrent melanoma was treated with combination ipilimumab and nivolumab and subsequently presented with progressive leg weakness, back pain, and difficulty ambulating. The diagnosis of mononeuritis multiplex was made, which was resistant to steroid pulses, chronic steroids, intravenous immunoglobulin, and rituximab. She developed progressive neurologic dysfunction and elected for hospice care. We found only two other cases reported in the literature. CONCLUSIONS: Increased awareness, prompt recognition, and aggressive treatments are likely the best opportunity for improved outcomes in this severe side effect.

Mononeuritis multiplex secondary to Lyme neuroborreliosis.

Lyme neuroborreliosis (LNB) typically presents as a painful radiculitis or a cranial mononeuropathy with lymphocytic meningitis (Bannwarth's syndrome). Isolated peripheral mononeuropathy or multiple mononeuropathy is less frequently recognised. A 58-year-old female with a background of IgA nephropathy and chronic kidney disease presented with a painful left ulnar neuropathy followed within 3 months by superficial radial neuropathy. Initial serum and cerebrospinal fluid (CSF) analysis were unremarkable; nerve conduction study was in keeping with a mononeuritis multiplex. A superficial radial nerve biopsy demonstrated inflammation with axonal injury consistent with a pathologically possible vasculitis. Borrelia antibodies were identified using enzyme-linked immunosorbent assay and immunoblot in serum consistent with active recent Lyme borreliosis. A 6-week course of doxycycline was initiated with gradual resolution of pain and improved power. A repeat nerve conduction study demonstrated improvement in sensory and motor responses. This case report identifies a peripheral nerve syndrome of a mononeuritis multiplex secondary to LNB in the absence of CSF pleocytosis with excellent outcome following antibiotic treatment. Peripheral nervous system manifestations of Lyme borreliosis can mimic a vasculitic neuropathy and therefore should be considered in individuals presenting with a painful mononeuritis multiplex.

Case report: Mononeuritis multiplex in the course of dengue fever.

BACKGROUND: Dengue fever usually presents as a self-limiting acute febrile illness with worsening thrombocytopenia, with a small minority of patients developing hemorrhagic or life-threatening complications. Organ specific manifestations like myocarditis, acalculous cholecystitis, encephalitis has been described but are uncommon presentations. Even more rarely, such manifestations are the presenting complaint of Dengue fever. In this case report, we highlight a case of Dengue fever where unrelated neuropathies were the presenting complaint. CASE PRESENTATION: An elderly man presents with 1 day of diplopia and left foot drop, associated with 2 days history of fever. A decreasing white cell count (WBC) and platelet on the 2nd day of admission prompted Dengue virus to be tested and a positive NS-1 antigen was detected, confirming the diagnosis of Dengue fever. He was treated with supportive treatment with a short duration of intravenous fluids recovered uneventfully and was discharged 6 days after admission with almost full resolution of diplopia and partial resolution of left foot drop. Left foot drop recovered completely 2 weeks later. CONCLUSION: Neurological manifestations can be the presenting symptoms in Dengue fever, a diagnosis which should be borne in mind when such symptoms present in patients from endemic areas or in returning travellers from these areas.

Improvement of pure sensory mononeuritis multiplex and IgG1 deficiency with sitagliptin plus Vitamin D3.

INTRODUCTION: Mononeuritis multiplex (MM) is an unusual form of peripheral neuropathy involving at least two noncontiguous peripheral nerve trunks. The pure sensory form of MM occurs rarely. Immunoglobulin (Ig)G subclass deficiency is a clinically and genetically heterogeneous disorder. Up to 50% of adults with selective subnormal IgG1 levels or selective IgG1 deficiency have a concomitant autoimmune disorder. Herein, we report the case of a patient with MM and selective IgG1 deficiency who showed remarkable clinical improvement after 2-year combination therapy with the DPP-4 inhibitor sitagliptin plus vitamin D3. CASE REPORT: A 49-year-old man developed numbness in right hand and forearm. After 6 months, the patient developed left forefoot numbness. Approximately 8 years later, the patient started to develop numbness also in the right forefoot, along with symptoms of evening fatigue and occasional orthostatic hypotension. The patient also reported recurrent candidiasis in glans and intergluteal areas since adolescence. Electromyoneurography of lower and upper limbs revealed the presence of multiple mononeuropathies. Protein electrophoresis showed hypogammaglobulinemia and low serum IgG1 levels. Sural nerve biopsy showed the presence of perineuritis. The patient was diagnosed with MM due to perineuritis probably secondary to IgG1 deficiency. We, then, proposed combination therapy with sitagliptin and vitamin D3 in the attempt to achieve immunomodulation. At the last follow-up visit (2 years), the patient showed persistent clinical improvement, increase in IgG1 levels and normalization of protein electrophoresis. CONCLUSIONS: To the best of our knowledge, this is the first case showing a remarkable clinical improvement of MM and selective IgG1 deficiency achieved through a combination therapy with sitagliptin and vitamin D3.

Eosinophilic granulomatosis with polyangiitis presenting with myositis: case based review.

Eosinophilic granulomatosis with polyangitis (EGPA) is a systemic necrotizing small-vessel vasculitis that presents heterogeneously as a multi-organ disease. EGPA evolves through three phases: (1) prodromic phase with asthma, atopy and sinusitis, (2) eosinophilic phase characterized by peripheral eosinophilia and eosinophilic infiltration without necrosis, and (3) vasculitic phase involving organ damage. EGPA often presents with asthma, mononeuritis multiplex, lung infiltrates, sinusitis and constitutional symptoms. Although myalgias are common, EGPA rarely presents with true weakness with elevated creatinine kinase (CK). We describe a rare case of a patient presenting with eosinophilic myositis, who subsequently developed fulminant EGPA. The patient's diagnosis was supported by an initial clinical presentation of weakness and elevated CK, followed by fleeting pulmonary infiltrates and mononeuritis multiplex, peripheral eosinophilia, and strongly positive myeloperoxidase anti-cytoplasmic antibody (MPO-ANCA). Muscle biopsy revealed eosinophilic myositis. The patient responded well to high-dose glucocorticoids and cyclophosphamide with improved symptoms and biochemical markers. Based on our literature review, there are only seven similar cases reported of EGPA presenting with myositis and confirmatory muscle biopsies. There is significant heterogeneity in their clinical findings, histopathology and treatments that were used. Our case report and literature review highlights the importance of recognizing myositis as an initial presenting symptom of EGPA, providing an opportunity for early diagnosis and treatment to reduce risk of further disease progression and morbidity.

Severe Mononeuritis Multiplex due to Rheumatoid Vasculitis in Rheumatoid Arthritis in Sustained Clinical Remission for Decades.

Rheumatoid vasculitis (RV) usually occurs in patients with refractory rheumatoid arthritis (RA). An 80-year-old woman was transferred to our hospital because of muscle weakness and paresthesia in all 4 limbs. She had been diagnosed with RA 30 years ago and achieved sustained clinical remission. At presentation, polyarthritis and drop foot were observed, and rheumatoid factor was prominently elevated. A peripheral nerve conduction test revealed mononeuritis multiplex in her limbs. We suspected that RV had developed rapidly despite RA having been stable for many years and started immunosuppression therapy with steroids combined with azathioprine. The treatment prevented worsening of muscle weakness and paresthesia.

[Multiple mononeuropathy associated with systemic sclerosis with vasculitis confirmed by nerve biopsy: a case report].

A 68-year-old woman with a medical history of interstitial pneumonia associated with systemic sclerosis (SSc) presented with numbness of the lower limbs and left drop foot. She was diagnosed with multiple mononeuropathy based on the laterality of her symptoms, muscle weakness, thermal hypoalgesia, and nerve conduction study findings. Left sural nerve biopsy showed vasculitis, and steroid therapy was effective. This case highlights the importance of histopathological assessment to select an appropriate treatment strategy.

An unusual complication of sacral nerve root injury following bone marrow harvesting: a case report.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) remains an important therapeutic option for many hematologic malignancies. Bone marrow harvesting from an appropriate donor must be conducted for hematopoietic stem cell transplantation (HSCT). Many previous studies show complications of the recipient after hematopoietic stem cell transplantation (HSCT). However, complications of the donor after bone marrow harvesting are rare. We here report a unique case of a patient who developed sacral nerve root injury after bone marrow harvesting. CASE PRESENTATION: A 26-year-old man was admitted to our medical center complaining of acute onset painful burning and tingling sensation at the left posterior thigh and calf. He was a bone marrow donor for his brother's bone marrow transplantation. He had underwent a bone marrow harvesting procedure two days before admission as a bone marrow donor, using both posterior superior iliac spine (PSIS) as the puncture site. Pelvic magnetic resonance image (MRI) showed enhancement around the left S2 nerve root in T1 and T2-weighted images. Nerve conduction studies (NCS) revealed normal conduction velocity and amplitude on both lower extremities. Electromyography (EMG) presented abnormal spontaneous activity and neurogenic motor unit potentials on the S2-innervated intrinsic foot muscle and gastrocnemius, soleus muscle on the left. The patient was treated with pregabalin for pain control. The patient was followed up after 3, 6, and 12 months. Neuropathic pain improved to Visual Analogue Scale (VAS) 1, and recovery state was confirmed by re-innervation patterns of motor unit potentials in electromyography. CONCLUSION: Bone marrow harvesting is a relatively safe procedure. However, variable complications may occur. Accurate anatomical knowledge and carefulness are required to avoid sacral nerve root injury when performing the bone marrow harvesting procedure.

Peripheral nervous system involvement in systemic lupus erythematosus: a retrospective study on prevalence, associated factors and outcome.

BACKGROUND: Despite its potentially significant impact on disease outcome, peripheral nervous system involvement in systemic lupus erythematosus has received little attention. OBJECTIVE: The objective of this study was to assess the prevalence and clinical features of peripheral nervous system involvement in a large cohort of systemic lupus erythematosus patients. METHODS: The records of systemic lupus erythematosus patients examined at two tertiary referral centres over a period of 14 years (from 2000 to 2014) were analyzed. Peripheral nervous system events were ascertained according to the 1999 American College of Rheumatology case definitions and by using an attribution algorithm for neuropsychiatric events. Prevalence of peripheral nervous system in systemic lupus erythematosus and demographic, clinical and laboratory features were assessed. Patients with peripheral nervous system events were compared with a control group of systemic lupus erythematosus patients without peripheral nervous system involvement. RESULTS: In a retrospective cohort of 1224 patients, the overall prevalence of peripheral nervous system involvement was 6.9% (85 patients, 95% confidence interval 0.06-0.08), with 68% of peripheral nervous system events attributable to systemic lupus erythematosus. Polyneuropathy was the most common manifestation observed (38 events, 39.2%), followed by cranial neuropathy in 30 cases (30.9%) and 12 cases of single (12.4%) or multiple (eight events, 8.2%) mononeuritis. The average age of systemic lupus erythematosus onset was significantly higher in patients with peripheral nervous system events than in controls (mean ± standard deviation: 45.9 ± 14.8 vs. 37.1 ± 14.0) and they were more likely to have higher SLEDAI-2K and SLICC/ACR Damage Index scores, as well as hypertension and livedo reticularis. A subgroup analysis of events deemed to be systemic lupus erythematosus-related provided similar results. CONCLUSION: Peripheral nervous system manifestations are a potential complication of systemic lupus erythematosus. Careful neurological assessment should therefore be included in the diagnostic workup of patients with systemic lupus erythematosus, especially in those with later onset and greater damage and disease activity.

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.

Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome) Complicated by Perforation of the Small Intestine and Cholecystitis.

We report a case of eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) complicated by perforation of the small intestine and necrotizing cholecystitis. A 69-year-old man with a history of bronchial asthma was admitted with mononeuritis multiplex. The laboratory findings included remarkable eosinophilia. He was treated with corticosteroids and his laboratory indices showed improvement; however, his functional deficits remained. His neuropathy gradually improved after the addition of intravenous immunoglobulin (IVIG). He was subsequently treated with oral prednisolone (40 mg/day) as maintenance therapy. Within a month after finishing IVIG, he developed perforation of the small intestine and necrotizing cholecystitis. Intestinal perforation has often been reported as a gastrointestinal complication of EGPA. In contrast, cholecystitis is a rare complication. We report this case because the manifestation of more than one complication is extremely rare. Gastrointestinal symptoms may be a complication of EGPA itself and/or immunosuppressive treatment.

Identification of a New Pyrazolo[1,5-a]quinazoline Ligand Highly Affine to γ-Aminobutyric Type A (GABAA) Receptor Subtype with Anxiolytic-Like and Antihyperalgesic Activity.

Compounds that can act on GABAA receptor subtype in a selective manner, without the side effects of classical benzodiazepine ligands, represent promising therapeutic tools in neurological disorder as well as for relief of pain or in comorbidity of anxiety states and depression. Continuing our research on GABAA receptor subtype ligands, here is reported the synthesis of a series of pyrazolo[1,5-a]quinazoline 3- and/or 8-substituted as 5-deaza analogues of previous reported pyrazolo[5,1-c][1,2,4]benzotriazine, already identified as selective GABAA receptor subtype ligands endowed with anxiolytic-like and antihyperalgesic action or enhancer cognition. Between the new compounds stands out 12b for its high affinity value (Ki = 0.27 nM) and for its anxiolytic-like and ability to relieve neuropathic painful conditions evaluated in CCI and STZ murine model.

[Etiopathogenetic factors of peripheral neuropathic pain in rheumatoid arthritis]. / Étiopatogeneticheskie faktory perifericheskoi neiropaticheskoi boli pri revmatoidnom artrite.

AIM: To determine a neuropathic component of pain and define its causes in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: One hundred and eighty-three patients with confirmed RA, mean age 46,5±11,7 years, RA duration from 3 month to 30 years, were studied. Rheumatology, neurological, using the DN4 questionnaire, examinations and stimulation electromyography were used. Results and сonclusion. Signs of neuropathic pain (NP) assessed with the DN4 were identified in 73 (43%) patients with RA. These patients were older, had longer RA duration as well as higher clinical stage of disease and reduced functional abilities. There were no correlation between NP and disease activity. Peripheral nervous system (PNS) lesions were seen in 96% patients with NP: sensory motor neuropathy (55%), tunnel syndrome (14%), mononeuropathy (19%) and their combinations (4%), cervical myelopathy (4%). PNS lesions is the main etiopathogenetic factor of peripheral NP in RA. This finding opens new perspectives for complex treatment, including group B vitamins, of chronic pain in RA.

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.