Ultrasonographic abnormalities in clinically unaffected nerves of patients with nonvasculitic motor and sensorimotor mononeuropathies.

INTRODUCTION/AIMS: Diagnostic criteria for multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensorimotor neuropathy (MADSAM) require the involvement of at least two peripheral nerves. However, many patients with very similar features have clinical involvement of only a single peripheral nerve, which may preclude their correct diagnosis and treatment. The present study aimed to present a cohort of such patients and discuss the role of ultrasonography (US) in their diagnosis. METHODS: Patients with nonvasculitic immune-mediated motor mononeuropathies (MM) and sensorimotor mononeuropathies (SMM) were recruited prospectively or identified from the electronic records. They were invited to comprehensive follow-up visits consisting of clinical examination, electrodiagnostic (EDx), and US studies. RESULTS: Twenty-four patients (13 men) were studied (11 with MM). The characteristics of MM and SMM patients were very similar to MMN and MADSAM, respectively. The US, in addition to a long-swollen segment (average length, 20 cm) in the clinically affected nerve, revealed nerve swelling in, on average, six additional sites in clinically unaffected nerves. DISCUSSION: In patients with clinical and EDx involvement of only a single nerve, an US demonstration of multifocal peripheral nerve swelling points to a more widespread, probably dysimmune mechanism. Further studies are needed to evaluate the value of US as a supplementary method for the diagnosis of MADSAM and MMN in patients with clinical involvement of a single nerve.

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.

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.

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.

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.

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 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.

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.

Peripheral neuropathy after burn injury.

OBJECTIVES: Peripheral neuropathy is a well-documented disabling sequela of major burn injury. These lesions are associated with both thermal and electrical injuries that may be frequently undiagnosed or overlooked in clinical settings. The purpose of this study was to evaluate the prevalence of burn-related neuropathy in our database and to investigate the clinical correlates for both mononeuropathy and generalized peripheral polyneuropathy. PATIENTS AND METHODS: Out of 648 burn patients, admitted to our clinic forty-seven burn patients with the diagnosis of peripheral neuropathy were evaluated retrospectively. The demographic and clinical data collected were gender, age, degree, site and percent surface area of burn, type of burn, and the results of electrodiagnostic examination, including electromyography and nerve conduction assessments and associated pathology if existed. RESULTS: Peripheral neuropathy is the most frequent disabling neuromuscular complication of burn, that may be undiagnosed or overlooked. In current study, peripheral neuropathy associated with burn all of our patients were identified by electrodiagnostic study. After treatment in Burn Unit, clinical and electrodiagnostic studies were applied. Motor and sensory distal latencies were prolonged and sensory nerve action potentials reduced in amplitude. CONCLUSIONS: The findings of our study have shown that polyneuropathies and axonal neuropathy were more frequent than mononeuropathy and demyelination.  

Tendon transfers for radial, median, and ulnar nerve palsy.

Tendon transfers are used to restore balance and function to a paralyzed, injured, or absent neuromuscular-motor unit. In general, tendon transfer is indicated for restoration of muscle function after peripheral nerve injury, injury to the brachial plexus or spinal cord, or irreparable injury to tendon or muscle. The goal is to improve the balance of a neurologically impaired hand. In the upper extremity, tendon transfers are most commonly used to restore function following injury to the radial, median, and ulnar nerves. An understanding of the general principles of tendon transfer is important to maximize the outcome.

Variation in recommendation for surgical treatment for compressive neuropathy.

PURPOSE: It is our impression that there is substantial, unexplained variation in hand surgeon recommendations for treatment of peripheral mononeuropathy. We tested the null hypothesis that specific patient and provider factors do not influence recommendations for surgery. METHODS: Using a web-based survey, hand surgeons recommended surgical or nonsurgical treatment for patients in 2 different scenarios. Six elements of the first scenario (symptoms, circumstances, mindset, diagnosis, objective testing, and expectations) had 2 possibilities that were each independently and randomly assigned to each rater. For the second scenario, 2 different scenarios were randomly assigned to each rater. Multivariable logistic regression sought factors associated with a recommendation for surgery. RESULTS: A total of 186 surgeons of the Science of Variation Group completed a survey regarding recommendation of surgery for 2 different patients based on clinical scenarios. Recommendations for surgery did not vary significantly according to provider characteristics. For the various elements in scenario 1, recommendation for surgery was more likely for patients who were self-employed and continued to work and who had objective electrodiagnostic abnormalities. For the 2 vignettes used in scenario 2, a recommendation for surgery was associated with abnormal electrophysiology. CONCLUSIONS: The findings of this study suggest that-at least in a survey setting-surgeons prefer to offer peripheral nerve decompression to patients with abnormal electrophysiology, particularly those with effective coping strategies. CLINICAL RELEVANCE: The role of objective verification of pathophysiology is debated, but it is an influential factor in recommendations for hand surgery.

Usefulness of assessing repeater F-waves in routine studies.

INTRODUCTION: Repeater F-waves are sometimes seen in routine studies. METHODS: We retrospectively reviewed the clinical significance of repeater F-waves in median, ulnar, and fibular nerve recordings in 50 healthy subjects and groups of 50 patients each with diabetic polyneuropathy, amyotrophic lateral sclerosis, carpal tunnel syndrome, ulnar mononeuropathy, and L5 root lesion. The number of identical F-waves and their repetitions in samples of 20 stimuli were estimated. RESULTS: Repeater F-waves occurred significantly more frequently in all nerves and patient groups than in healthy individuals. Their persistence was negatively correlated with that of non-repeater F-waves. CONCLUSIONS: Based on the presented material and recording condition it appears that repeater F-waves differentiate between health and disease but not between different types of pathology of motor neurons or their axons. Even in routinely recorded samples of 20 traces, the index of repeater all F-waves could be used as a sign of nerve pathology.

Polyarthritis and posterior interosseous nerve palsy associated with gastric carcinoma.

Cancer polyarthritis is a very rare condition. Here, we present a case of cancer polyarthritis, who also had mononeuritis simplex as a manifestation of paraneoplastic neuralgic syndrome. A 71-year-old man, who initially presented symmetrical polyarthritis and unilateral posterior interosseous nerve palsy, was subsequently diagnosed to have gastric cancer. Total gastrectomy was performed, and his polyarthritis and the palsy simultaneously disappeared within 2 weeks after the resection. His gastric cancer was found to be metastasized to his liver 16 months after the total gastrectomy; however, the polyarthritis and the palsy did not recurrent throughout his course. The polyarthritis in this case was diagnosed as a cancer polyarthritis from its features. On the other hand, the isolated posterior interosseous nerve palsy in this case met the diagnostic criteria for paraneoplastic neurological syndrome. This case was also unique in that the manifestations of paraneoplastic syndromes did not recur even after the metastasis of the primary cancer, suggesting that some specific clones in the cancer were responsive to the manifestations of paraneoplastic syndromes. Our case suggested that relapse of the manifestations of paraneoplastic syndromes may not always herald the recurrence of primary or metastatic tumour, and other tumour markers and signs should be periodically followed to search for the recurrence of the tumours.

Punched nerve syndrome: ultrasonographic appearance of functional vascular nerve impairment.

PURPOSE: The mechanical impact of a neighboring vessel on a "punched" nerve segment is thought to be one possible cause of compression neuropathy but has not been proven definitively. We report on 9 subjects with unclear clinical mononeuropathies in whom we could clearly define peripheral nerve impairment by such vessels on real-time high-resolution ultrasound (HRUS). MATERIALS AND METHODS: Nine subjects with unclear mononeuropathy based on clinical neurological examination were referred to our department for HRUS assessment. The shape, inner and outer echotexture, size and diameter, and overall integrity of these nerves were assessed including an exact analysis of the surrounding soft tissues to search for potentially extraneural pathology. This included duplex imaging to identify even tiny atypical vascular structures. RESULTS: In all patients duplex HRUS showed the pulsatile and "punching" character of the relevant vessels and the direct mechanical impact of these vessel. The involved nerve segments appeared enlarged with a hypoechoic change of echotexture including at least partial masking of their inner fascicular texture. CONCLUSION: Although rare, a "punching" vessel can be the cause of a compression neuropathy. Therefore, duplex HRUS must be included in every HRUS examination of patients with otherwise unclear mononeuropathy.

The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats.

BACKGROUND: Neuropathic pain is a chronic disease resulting from dysfunction within the "pain matrix". The basolateral amygdala (BLA) can modulate cortical functions and interactions between this structure and the medial prefrontal cortex (mPFC) are important for integrating emotionally salient information. In this study, we have investigated the involvement of the transient receptor potential vanilloid type 1 (TRPV1) and the catabolic enzyme fatty acid amide hydrolase (FAAH) in the morphofunctional changes occurring in the pre-limbic/infra-limbic (PL/IL) cortex in neuropathic rats. RESULTS: The effect of N-arachidonoyl-serotonin (AA-5-HT), a hybrid FAAH inhibitor and TPRV1 channel antagonist, was tested on nociceptive behaviour associated with neuropathic pain as well as on some phenotypic changes occurring on PL/IL cortex pyramidal neurons. Those neurons were identified as belonging to the BLA-mPFC pathway by electrical stimulation of the BLA followed by hind-paw pressoceptive stimulus application. Changes in their spontaneous and evoked activity were studied in sham or spared nerve injury (SNI) rats before or after repeated treatment with AA-5-HT. Consistently with the SNI-induced changes in PL/IL cortex neurons which underwent profound phenotypic reorganization, suggesting a profound imbalance between excitatory and inhibitory responses in the mPFC neurons, we found an increase in extracellular glutamate levels, as well as the up-regulation of FAAH and TRPV1 in the PL/IL cortex of SNI rats. Daily treatment with AA-5-HT restored cortical neuronal activity, normalizing the electrophysiological changes associated with the peripheral injury of the sciatic nerve. Finally, a single acute intra-PL/IL cortex microinjection of AA-5-HT transiently decreased allodynia more effectively than URB597 or I-RTX, a selective FAAH inhibitor or a TRPV1 blocker, respectively. CONCLUSION: These data suggest a possible involvement of endovanilloids in the cortical plastic changes associated with peripheral nerve injury and indicate that therapies able to normalize endovanilloid transmission may prove useful in ameliorating the symptoms and central sequelae associated with neuropathic pain.

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.