Sacral dural arteriovenous fistula mimicking multiple mononeuropathy.

A sacral dural arteriovenous fistula (dAVF) is extremely rare, and the pathophysiological and clinical features have not been established. A 70-year-old man developed gradually progressive right-dominant bilateral sensory disorder of the lower limbs. His clinical course and electrophysiological findings were similar to those of multiple mononeuropathy. However, angiography showed a sacral dAVF at the right intervertebral foramen between the fifth lumbar and first sacral vertebrae. Endovascular embolization of the dAVF improved his clinical symptoms and electrophysiological findings. A sacral dAVF can mimic multiple mononeuropathy in terms of its clinical features and electrophysiological findings. A sacral dAVF is a treatable disease and should be considered as a differential diagnosis of lower extremity disorders.

Polyangiitis overlap syndrome: a novel presentation of microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis.

Polyangiitis overlap syndrome (POS) is a diagnostic term coined by Leavitt and Fauci that characterises patients with overlapping features of more than one vasculitis. Prior case studies of antineutrophil cytoplasmic antibodies (ANCA)-associated POS have only been published in patients with eosinophilic granulomatosis with polyangiitis (EGPA) and granulomatosis with polyangiitis alongside proteinase-3/cytoplasmic (C)-ANCA positivity. We present a case of a 60-year-old woman with dyspnoea, hemoptysis, positive perinuclear-ANCA and renal biopsy demonstrating evidence of microscopic polyangiitis. In addition, our patient also had asthma, mononeuritis multiplex, eosinophilia and migratory pulmonary infiltrates, thus fulfilling the criteria for EGPA. This novel case report suggests that POS is not limited to C-ANCA positivity and has variable presentations.

Sensitivity and specificity of single and combined clouds analyses compared with quantitative motor unit potential analysis.

INTRODUCTION: Turns-amplitude, number of small segments (NSS)-activity, and envelope-activity clouds are three methods of electromyography (EMG) interference pattern analysis. Our objective was to evaluate the sensitivity and specificity of each individual cloud analysis and combined clouds analysis to compare with that of quantitative motor unit potential (QMUP) analysis. METHODS: A total of 379 muscles from 100 patients were analyzed by both QMUP and clouds analyses. Calculation of sensitivity and specificity was based on the clinical diagnosis as the "gold standard." RESULTS: For discrimination of abnormal vs normal and neuropathic vs non-neuropathic, combined clouds analysis had greater sensitivity than QMUP analysis and any single cloud analysis, but there were no differences in specificity. For discrimination of myopathic vs non-myopathic, combined clouds analysis and single cloud analysis had greater sensitivity than QMUP analysis, but there were no differences in specificity. DISCUSSION: Combined clouds analysis was superior to QMUP and each single cloud analysis for distinguishing normal, myopathic, and neuropathic muscles.

Utility of neuromuscular ultrasound in the investigation of common mononeuropathies in everyday neurophysiology practice.

INTRODUCTION: In everyday clinical neurophysiology practice, mononeuropathies are evaluated primarily by traditional electrodiagnostic testing. We sought to assess the additional benefit of neuromuscular ultrasound (US) in this scenario. METHODS: All consecutive mononeuropathies undergoing combined US and electrodiagnostic evaluation over a 23-mo period at a single neurophysiology practice were reviewed. Three independent examiners assessed how often US was: (a) "contributory" - enabling a definite diagnosis not made by electrophysiology alone and/or impacting on the therapeutic decision, (b) "confirmatory" of the electrodiagnostic findings, but not adding further diagnostic or therapeutic information, or (c) "negative" - missed the diagnosis. RESULTS: There were 385 studies included. US was "contributory" in 36%, "confirmatory" in 61% and "negative" in 3%. DISCUSSION: In this study of everyday neurophysiology practice, neuromuscular US contributed significant diagnostic or therapeutic information in over 1/3 of the investigations for common mononeuropathies. False negative US studies were uncommon in this setting.

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.

Peripheral Nervous System Disease in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study.

OBJECTIVE: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. RESULTS: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy. CONCLUSION: PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.

A Salivation Abnormality with Trigeminal Nerve Dysfunction in Dogs.

Trigeminal nerve pathology can lead to sensory and motor dysfunction to structures of the head that are easily recognized. The trigeminal nerve is a conduit for the distribution of postganglionic parasympathetic innervation to structures of the head. Parasympathetic innervation to the salivary glands is provided by preganglionic parasympathetic neurons of the facial and glossopharyngeal nerves. Postganglionic axons course with branches of the mandibular branch of the trigeminal nerve to reach the salivary glands. Denervation of the salivary glands impacts glandular function, leading to a reduction in the volume and composition of the saliva produced. Saliva plays an important role in oral health. Poor oral health has widespread systemic implications. This article describes a group of dogs with unilateral or bilateral dysfunction of the trigeminal nerve and/or its branches. In all dogs, an accumulation of thick, foamy saliva was observed accumulating in the dorsal aspect of the caudal oral cavity on the ipsilateral side to the affected nerve. In dogs with magnetic resonance imaging (MRI), there was a reduction in size based on the largest cross-sectional area measurement and an increase in mean signal intensity of the salivary glands ipsilateral to the affected nerves compared to the glands on the normal side. The authors hypothesize that the abnormal saliva and MRI changes observed were consequent to parasympathetic denervation of the salivary glands. The recognition of this clinical observation is the first step in understanding the impact that denervation has on salivation and ultimately on overall oral and systemic health in dogs.

Involvement of galanin and galanin receptor 2 in nociceptive modulation in anterior cingulate cortex of normal rats and rats with mononeuropathy.

The present study was performed to explore the role of galanin and galanin receptor 2 in nociceptive modulation in anterior cingulate cortex (ACC) of normal rats and rats with mononeuropathy. Intra-ACC injection of galanin induced significant increases in hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulations in both normal rats and rats with mononeuropathy, the increased HWLs were attenuated significantly by intra-ACC injection of galanin receptor 2 antagonist M871, indicating an involvement of galanin receptor 2 in nociceptive modulation in ACC. Interestingly, the galanin-induced HWL was significant higher in rats with mononeuropathy than that in normal rats tested by Randall Selitto test. Furthermore, both the galanin mRNA expression and galanin content increased significantly in ACC in rats with mononeuropathy than that in normal rats. Moreover, both the mRNA levels of galanin receptor 2 and the content of galanin receptor 2 in ACC increased significantly in rats with mononeuropathy than that in normal rats. These results found that galanin induced antinociception in ACC in both normal rats and rats with mononeuropathy. And there may be plastic changes in the expression of galanin and galanin receptor 2 in rats with mononeuropathy, as well as in the galanin-induced antinociception.

Diagnosing and attributing neuropsychiatric events to systemic lupus erythematosus: time to untie the Gordian knot?

Neurological and psychiatric syndromes, collectively referred to as NPSLE, occur frequently in SLE. The frequency of NPSLE varies from 21 to 95%; however, only 13-38% of neuropsychiatric (NP) events could be attributable to SLE in the NPSLE SLICC inception cohort. This variability in the frequency of NPSLE is attributable to the low specificity of the ACR case definitions for SLE-attributed NP syndromes, inclusion of minor NP events in the ACR nomenclature, difficulty in ascertainment of NP events and diverse experience of rheumatologists in the clinical assessment of NP events. Making the correct and early attribution of NP events to SLE is important to institute appropriate immunosuppressive treatment for favourable outcomes. Various attribution models using composite decision rules have been developed and used to ascribe NP events to SLE. This review will focus on the various clinical presentations, diagnostic work-up and attributions of the common NPSLE syndromes, including other NP events not included in the ACR nomenclature but which have come to attention in recent years.

Analysis of spontaneous activity of superficial dorsal horn neurons in vitro: neuropathy-induced changes.

The superficial dorsal horn contains large numbers of interneurons which process afferent and descending information to generate the spinal nociceptive message. Here, we set out to evaluate whether adjustments in patterns and/or temporal correlation of spontaneous discharges of these neurons are involved in the generation of central sensitization caused by peripheral nerve damage. Multielectrode arrays were used to record from discrete groups of such neurons in slices from control or nerve damaged mice. Whole-cell recordings of individual neurons were also obtained. A large proportion of neurons recorded extracellularly showed well-defined patterns of spontaneous firing. Clock-like neurons (CL) showed regular discharges at ∼6 Hz and represented 9 % of the sample in control animals. They showed a tonic-firing pattern to direct current injection and depolarized membrane potentials. Irregular fast-burst neurons (IFB) produced short-lasting high-frequency bursts (2-5 spikes at ∼100 Hz) at irregular intervals and represented 25 % of the sample. They showed bursting behavior upon direct current injection. Of the pairs of neurons recorded, 10 % showed correlated firing. Correlated pairs always included an IFB neuron. After nerve damage, the mean spontaneous firing frequency was unchanged, but the proportion of CL increased significantly (18 %) and many of these neurons appeared to acquire a novel low-threshold A-fiber input. Similarly, the percentage of IFB neurons was unaltered, but synchronous firing was increased to 22 % of the pairs studied. These changes may contribute to transform spinal processing of nociceptive inputs following peripheral nerve damage. The specific roles that these neurons may play are discussed.

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.

The significance of muscle echo intensity on ultrasound for focal neuropathy: The median- to ulnar-innervated muscle echo intensity ratio in carpal tunnel syndrome.

OBJECTIVE: The objective of this study was to investigate the usefulness of muscle ultrasound for evaluating muscle changes caused by denervation in carpal tunnel syndrome (CTS), which is a focal neuropathy. METHODS: The mean and standard deviation (SD) of echo intensity (EI) in the thenar and hypothenar muscles were calculated in 35 patients with CTS and 11 healthy subjects. Patients were assigned to three subgroups based on CTS severity as determined by electrodiagnostic tests. The ratio of thenar muscle pixel brightness to hypothenar muscle pixel brightness was used in statistical analyses. The ratio of mean pixel brightness was termed the EI ratio, and the ratio of the SD of pixel brightness was termed the inhomogeneity ratio. RESULTS: Both the EI ratio and the inhomogeneity ratio were significantly higher in the patient group than in the control group. In a comparison of the three patient subgroups, the severe group showed significant differences in both the EI and inhomogeneity ratios compared to the other two groups. Subjects with denervation potential in the abductor pollicis brevis (APB) had higher EI and inhomogeneity ratios than subjects without denervation potential in the APB. CONCLUSION: The EI ratio and inhomogeneity ratio are useful variables with which to evaluate disease severity and the presence of denervation in patients with CTS. SIGNIFICANCE: Muscle ultrasound has clinical significance in the detection of muscle changes that result from neuropathy.

[A clinical-electroneuromyographic study of the efficacy of ipidacrine in patients with mononeuropathies].

OBJECTIVE: To evaluate the efficacy and tolerability of axamon (ipidacrine) therapy in patients with focal neuropathies--mononeuropathies. MATERIAL AND METHODS: We examined 35 patients, aged 18 years and older, with focal neuropathies (tunnel syndromes, radiculopathies). In the main group (n=20) axamon (ipidacrine) was prescribed in addition to the basic (standard) therapy (group B vitamins, lipoic acid) during 6 week, in the control group (n=15) patients remained only on the basic (standard) treatment. RESULTS: In the main group positive clinical changes were accompanied by the more significant positive electroneuromyographic (ENMG) dynamics as compared to the control group (the increased amplitude of M-response in the muscles of the hand and feet; increased nerve conduction velocity in the peripheral nerves as a manifestation of remyelination activity, and others). CONCLUSION: The obtained clinical and ENMG data indicate that axamon (ipidacrine) is a unique cholinesterase inhibitor with conduction action primarily targeting on efferent (motor) fibers of the peripheral nerves.

The effects of intraplantar and intrathecal botulinum toxin type B on tactile allodynia in mono and polyneuropathy in the mouse.

BACKGROUND: Mononeuropathies (MNs: nerve ligation) and polyneuropathies (PNs: cisplatin) produce unilateral and bilateral tactile allodynia, respectively. We examined the effects of intraplantar (IPLT) and intrathecal (IT) botulinum toxin B (BoNT-B) on this allodynia. METHODS: Mice (male c57Bl/6) were prepared with an L5 nerve ligation. Others received cisplatin (IP 2.3 mg/kg/d, every other day for 6 injections). Saline and BoNT-B were administered through the IPLT or IT route. We examined mechanical allodynia (von Frey hairs) before and at intervals after BoNT. As a control, we injected IPLT BoNT-B treated with dithiothreitol to cleave heavy chain from light chain. We measured motor function using acute thermal escape and sensorimotor tests. RESULTS: MN and PN mice showed a persistent ipsilateral and bilateral allodynia, respectively. IPLT BoNT-B resulted in an ipsilateral dorsal horn reduction in the synaptic protein target of BoNT-B (vesicle-associated membrane protein) and a long-lasting (up to approximately 17 days) reversal of allodynia in PN and MN models. The predominant effect after IPLT delivery was ipsilateral to IPLT BoNT. The effects of IPLT BoNT-B in MN mice were blocked by prior reduction of BoNT-B with dithiothreitol. IT BoNT-B in mice with PN resulted in a bilateral reversal of allodynia. With these dosing parameters, hind paw placing and stepping reflexes were unaltered, and there were no changes in thermal escape latencies. After cisplatin, dorsal root ganglions displayed increases in activation transcription factor 3, which were reduced by IT, but not IPLT BoNT-B. CONCLUSIONS: BoNT-B given IPLT and IT yields a long-lasting attenuation of the allodynia in mice displaying MN and PN allodynia.

Intra-nucleus accumbens administration of the calcium/calmodulin-dependent protein kinase II inhibitor AIP induced antinociception in rats with mononeuropathy.

Calcium/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine- dependent protein kinase, which has been implicated in pain modulation at different levels of the central nervous system. The present study was performed in rats with mononeuropathy induced by left common sciatic nerve ligation. Unilateral sciatic nerve loose ligation produced decreases in the hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation. Intra-nucleus accumbens (NAc) injection of 3 µg, 6 µg and 12 µg of myristoylated autocamtide-2-inhibitory peptide (AIP), the CaMKII inhibitor, dose-dependently increased the HWL to noxious thermal and mechanical stimulation in rats with mononeuropathy. Furthermore, intra-NAc administration of morphine, the HWL to noxious thermal and mechanical stimulation increased markedly, and there were no significant differences between morphine group and AIP group. Taken together, the results showed that intra-NAc injection of AIP induced significant antinociceptive effects in rats with mononeuropathy, indicating that CaMKII may play an important role in the transmission and/or modulation of nociceptive information in the NAc in rats with mononeuropathy.

Nerve demyelination increases metabotropic glutamate receptor subtype 5 expression in peripheral painful mononeuropathy.

Wallerian degeneration or nerve demyelination, arising from spinal nerve compression, is thought to bring on chronic neuropathic pain. The widely distributed metabotropic glutamate receptor subtype 5 (mGluR5) is involved in modulating nociceptive transmission. The purpose of this study was to investigate the potential effects of mGluR5 on peripheral hypersensitivities after chronic constriction injury (CCI). Sprague-Dawley rats were operated on with four loose ligatures around the sciatic nerve to induce thermal hyperalgesia and mechanical allodynia. Primary afferents in dermis after CCI exhibited progressive decreases, defined as partial cutaneous denervation; importantly, mGluR5 expressions in primary afferents were statistically increased. CCI-induced neuropathic pain behaviors through the intraplantar injections of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective mGluR5 antagonist, were dose-dependently attenuated. Furthermore, the most increased mGluR5 expressions in primary afferents surrounded by reactive Schwann cells were observed at the distal CCI stumps of sciatic nerves. In conclusion, these results suggest that nerve demyelination results in the increases of mGluR5 expression in injured primary afferents after CCI; and further suggest that mGluR5 represents a main therapeutic target in developing pharmacological strategies to prevent peripheral hypersensitivities.