Recurrent brachial plexopathy as initial presentation of systemic lupus erythematosus: A case report and review of the literature.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects many organs of the body including the peripheral nervous system (PNS) which has potential significant impact. Plexopathy is rare but one of the serious PNS manifestations of lupus. CASE: A 41-year-old female presented with recurrent attacks of painful brachial plexopathy and right hemi-diaphragmatic paralysis. After extensive workup, she was diagnosed with SLE and started on hydroxychloroquine and mycophenolate mofetil. The frequency and severity of the attacks of plexopathy has significantly improved after starting the immune suppressive therapy for SLE. Whole exome sequencing unveiled previously unreported mutations encoding non-synonymous amino acids in titin and minichromosome maintenance 3-associated protein. CONCLUSION: Recurrent attacks of painful brachial plexopathy may warrant careful evaluation for underlying SLE with a premise of therapeutic benefit.

Upregulation of JHDM1D-AS1 alleviates neuroinflammation and neuronal injury via targeting miR-101-3p-DUSP1 in spinal cord after brachial plexus injury.

BACKGROUND: Neuroinflammation in the spinal cord following acute brachial plexus injury (BPI) remains a vital cause that leads to motor dysfunction and neuropathic pain. In this study, we aim to explore the role of long non-coding RNA JHDM1D antisense 1 (JHDM1D-AS1) in mediating BPI-induced neuroinflammation and neuronal injury. METHODS: A total brachial plexus root avulsion (tBPRA) model in adult rats and IL-1ß-treated motor neuron-like NSC-34 cells and LPS-treated microglia cell line BV2 were conducted for in vivo and in vitro experiments, respectively. The expressions of JHDM1D-AS1, miR-101-3p and DUSP1, p38, NF-κB, TNF-α, IL-1ß, and IL-6 were detected by RT-PCR and western blot seven days after tBPI. Immunohistochemistry (IHC) was used to detect neuronal apoptosis. CCK8 assay, Tunel assay and LDH kit were used for the detection of neuronal injury. The targeted relationships between JHDM1D-AS1 and miR-101-3p, miR-101-3p and DUSP1 were verified by RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assay. RESULTS: We found significant downregulated expression of JHDM1D-AS1 and DUSP1 but upregulated expression of miR-101-3p in the spinal cord after tBPI. Overexpression of JHDM1D-AS1 had a prominent neuroprotective effect by suppressing neuronal apoptosis and microglial inflammation through reactivation of DUSP1. Further exploration revealed that JHDM1D-AS1 may act as a competitive endogenous RNA targeting miR-101-3p, which bound on the 3'UTR of DUSP1 mRNA. In addition, overexpression of miR-101-3p could reverse the neuroprotective effects of JHDM1D-AS1 upregulation by blocking DUSP1. CONCLUSIONS: JHDM1D-AS1 exerted neuroprotective and anti-inflammatory effects in a rat model of tBPI by regulating miR-101-3p/DUSP1 axis.

Extrarenal rhabdoid tumor presented with an immobile arm in a one-year-old boy.

Infants with an immobile arm may be easily overlooked in primary care settings. Differential diagnoses include injuries, infections, neuropathies, ischemia and rarely, neoplasms. We report the case of a one-year-old boy with weakness in his left arm after minor trauma with a diagnosis of brachial plexus palsy initially. After rehabilitation for 2months, his weakness progressed to unsteady gait and quadriparesis. MRI revealed a huge solid tumor in the left supraclavicular fossa, which also involved the left brachial plexus, upper thoracic cavity, and left paravertebral space with invasion into the spinal canal. Microscopically, the medium-large polygonal tumor cells had an eccentric eosinophilic cytoplasm and immunostaining showed a loss of nuclear INI1 expression. Array comparative genomic hybridization of the tumor tissue confirmed a segmental deletion at chromosome region 22q11.23 involving the SMARCB1 gene. The final diagnosis was cervical paravertebral malignant rhabdoid tumor with intraspinal epidural and intradural invasion, a rare case of extrarenal extracranial rhabdoid tumor (ERRT). The intraspinal part of the tumor was resected followed by interval-compressed chemotherapy with vincristine-doxorubicin-cyclophosphamide alternating with ifosfamide-etoposide (VDC/IE). The tumor showed very good partial response to four cycles of chemotherapy with gradual recovery of neurological symptoms. ERRT is a very rare and aggressive tumor that mainly occurs in infants and children and may manifest with vague neurological symptoms when it involves the spinal cord and/or peripheral nerves. A neoplasm such as ERRT originating from or involving the brachial plexus should be considered in the differential diagnosis of an immobile arm in infancy.

CTNNB1 Mutations and Estrogen Receptor Expression in Neuromuscular Choristoma and Its Associated Fibromatosis.

Neuromuscular choristoma (NMC) is a very rare, developmental malformation characterized by the endoneurial intercalation of mature muscle fibers among peripheral nerve fibers. NMC typically arises in the major proximal peripheral nerves, most commonly the sciatic nerve, and may involve the lumbosacral and brachial plexus. Patients present clinically with progressive neuropathy or plexopathy. NMC is strongly associated with development of a fibromatosis, histologically identical to conventional desmoid-type fibromatosis (NMC-fibromatosis). The development of NMC-fibromatosis is often precipitated by iatrogenic trauma (ie, biopsy). Desmoid-type fibromatosis is characterized by CTNNB1 exon 3 mutations, which result in aberrant nuclear ß-catenin localization and dysregulated canonical Wnt signaling. In contrast, the pathogenesis of NMC and NMC-fibromatosis is unknown. Desmoid-type fibromatosis expresses estrogen receptors (ER), specifically the ER-beta isoform (ERß), and endocrine therapies may be used in surgically unresectable cases. In contrast, the ER expression profile of NMC-fibromatosis is unknown. We evaluated a series of NMC and NMC-fibromatosis for CTNNB1 mutations, ß-catenin expression, and ER isoform expression. Five NMCs occurred in 2 female and 3 male patients (median age: 14 y, range <1 to 42 y), as masses involving the sciatic nerve (N=4) or brachial plexus (N=1). Four (of 5) NMCs had CTNNB1 mutations: 3 c.134 C>T (p.S45F) and 1 c.121 A>G (p.T41A). Four patients subsequently developed NMC-fibromatosis, and all 4 cases contained CTNNB1 mutations, including 1 p.T41A and 3 p.S45F mutations. In 3 patients, the NMC and NMC-fibromatosis had identical CTNNB1 mutations. Only 1 NMC had no detectable CTNNB1 mutation; however, the patient's subsequent NMC-fibromatosis had a CTNNB1 p.T41A mutation. All NMC and NMC-fibromatosis showed aberrant nuclear localization of ß-catenin, nuclear ERß expression, and no ERα expression. The presence of CTNNB1 mutations both in NMC and NMC-fibromatosis may be a shared molecular genetic abnormality underlying their pathogenesis.

Proximal arm weakness is the most common presentation in young Korean soldiers diagnosed as having hereditary neuropathy with liability to pressure palsy (HNPP).

OBJECTIVES: Because patients with hereditary neuropathy with liability to pressure palsy (HNPP) are diagnosed mostly in their 20s, they are likely to experience their first major neurological symptoms during military training. We aimed to analyse the clinical characteristics and electrodiagnostic study findings of patients diagnosed with HNPP during their military service. METHODS: We identified patients diagnosed as having HNPP in 2011-2014 and investigated their initial symptom presentation, the location and severity of their weakness, the causative event, the results of electrodiagnostic studies and the results of the genetic analysis of the PMP-22 gene. RESULTS: Among the 36 patients included in the study, 19 (52.8%) patients had upper extremity paraesthesia with proximal arm weakness caused by brachial plexus lesion. Distal upper extremity symptoms were found in 12 (33.3%) patients, and leg paraesthesia was present only in five (13.9%) patients. Among the 19 patients who had proximal arm weakness, the most common cause of weakness was the performance of push-ups as a punishment (36.8%), and strenuous push-up exercise was the second cause of this symptom (21.1%). CONCLUSIONS: Brachial plexus lesion leading to proximal arm weakness and paraesthesia was the most common presentation in soldiers with HNPP, and strenuous push-up activity was the major leading causative event in this condition.

Expression profiles of MiRNAs for intrinsic musculature of the forepaw and biceps in the rat model simulating irreversible muscular atrophy of obstetric brachial plexus palsy.

Clinically in obstetric brachial plexus palsy (OBPP), irreversible atrophy of intrinsic musculature of the hand in denervation occurs much earlier than that of denervated arm muscles. With the aim of finding clues to explain this, the miRNA expression profile of denervated intrinsic musculature of the forepaw (IMF) and that of the denervated biceps were examined by microarray screening in the rat model simulating irreversible muscular atrophy caused by pan-plexus lesions of OBPP, and potential targets of specifically dysregulated miRNAs were predicted with use of bioinformatics analysis. It was found that denervated IMF and biceps had their own specifically dysregulated miRNAs, respectively, as compared with control. Analysis of Gene Ontology and of pathway showed that those specifically dysregulated miRNAs and their target genes might participate in self-regulation of neuromuscular junctions (NMJs). These outcomes suggest that self-regulative mechanism of NMJs may be different between denervated IMF and denervated biceps in the rat model simulating irreversible muscular atrophy of OBPP.

Surgical and postpartum hereditary brachial plexus attacks and prophylactic immunotherapy.

INTRODUCTION: Surgery and childbirth can trigger attacks of hereditary brachial plexus neuropathy (HBPN), and inflammation was suggested as a component of the pathogenesis. METHODS: HBPN patients who underwent surgery or parturition from January 1, 1996 to December 31, 2009 were studied. RESULTS: Twenty-five HBPN patients underwent 48 surgeries or parturitions. Seventeen patients (68%) had attacks, including 13 periprocedural and 7 postpartum by varied anesthesia types. Three patients who had 8 earlier combined attacks (after thyroidectomy, laminectomy, and Caesarean section) were given prophylactic immunosuppressive therapy (corticosteroids ± immunoglobulin). None suffered postoperative attacks, which is uncharacteristic of their prior experience. Five had perioperative attacks as their first HBPN manifestation. Median follow-up was 11 months (3-48 months). Attacks occurred in the operated limb (n = 6) or distant (n = 7) to surgical sites. All attacks interfered with daily living, with frequent incomplete recovery. Five patients had a SEPT9 mutation. CONCLUSIONS: Corticosteroids may prevent parturition and surgical HBPN attacks in some patients. Diverse surgeries, anesthesia, and childbirth frequently trigger HBPN attacks.

Axonal degeneration in peripheral nerves in a case of Leber hereditary optic neuropathy.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is a mitochondrial DNA (mtDNA) genetic disorder characterized by profound bilateral loss of central vision due to selective loss of retinal ganglion cells. Most patients with LHON do not have complaints related to the peripheral nervous system. We investigated possible qualitative and quantitative histological changes in the peripheral nerve of a patient with LHON as compared to normal controls. METHODS: Brachial plexus specimens were obtained at necropsy from a patient with LHON carrying the 3460/ND1 mtDNA mutation and age-matched controls without known history of neurological disease. The nerves were evaluated by light microscope coupled to a digital camera-based morphometric analysis and electron microscopy. RESULTS: Extensive axonal degeneration of the large heavily myelinated fibers was found in the brachial plexus from the patient with LHON. In LHON nerve fascicles, we counted over 10 times as many degenerated profiles as found in the control nerve fascicles. CONCLUSIONS: Microscopic examination of the brachial plexus in the patient with LHON clearly demonstrated a significant pattern of neurodegeneration. Our study suggests that peripheral neuropathy may be a subclinical feature associated with LHON.

[Effect of the heat shock protein 27 on NOS expression of spinal cord anterior hornmotoneurons after brachial plexus avulsion].

AIM: To observe the effect of heat shock protein 27 (Hsp27) on nitric oxide synthase (NOS) of spinal cord anterior horn after brachial plexus roots avulsion. METHODS: Sixty male adult Wistar rats were divided into control and experiment groups at random. The experiment group subjected to heat shock under 45 degrees C for 15 min, and maintained under 42 degrees C for 20 min subsequently. After recovering 24 h under the room temperature, the nerves of brachial plexus were avulsion with microhemostatic forcep. In a span from 12 h to 7 d, these animals were killed at different time. But the control group only received the surgery of the nerve roots of brachial plexus avulsion. The freeze sections of spinal cord were stained by NADPH-d histochemistry, HSP27 immunohistochemical. RESULTS: (1) In experiment group, the motoneuron began to express NOS abundantly at 12 h after avulsion (A=0.13625). Then the NOS-positive neurons declined quickly, but in control group, the motoneuron began to express NOS at the 5th day after lesion. (2) Hsp27 begin to show the peak at 1 d in experiment and control groups, but the experiment group were more strong than the control group. CONCLUSION: Hsp27 inhibited NOS of motoneuron after avulsion and brought into full play the cytoprotection.

SEPT9 mutations and a conserved 17q25 sequence in sporadic and hereditary brachial plexus neuropathy.

BACKGROUND: The clinical characteristics of sporadic brachial plexus neuropathy (S-BPN) and hereditary brachial plexus neuropathy (H-BPN) are similar. During attacks, inflammation of the brachial plexus nerves has been identified in both conditions. SEPT9 mutations (Arg88Trp, Ser93Phe, 5'UTR c.-131G>C) occur in some families with H-BPN. These mutations were not found in North American kindreds with H-BPN with a conserved 500-kilobase sequence of DNA at the 17q25 chromosomal region (where SEPT9 localizes) where a founder mutation has been suggested. OBJECTIVE: To study the 17q25 sequence and SEPT9 in S-BPN (56 individuals) and H-BPN (13 kindreds). METHODS: Allele analysis at 17q25, SEPT9 DNA sequencing, and messenger RNA analysis from lymphoblast cultures were performed. RESULTS: A conserved 17q25 sequence was found in 5 of 13 kindreds with H-BPN and 1 individual with S-BPN. This conserved sequence was not found in the family with a SEPT9 mutation (Arg88Trp) or in 182 control subjects. SEPT9 messenger RNA expression levels did not differ between forms of H-BPN and control subjects. No known mutations of SEPT9 were found in S-BPN. CONCLUSIONS: Rarely, individuals with S-BPN may have the same conserved 17q25 sequence found in many North American kindreds with H-BPN. Individuals with BPN with this conserved sequence do not seem to have SEPT9 mutations or alterations of messenger RNA expression levels in lymphoblast cultures and are predicted to have the most common genetic cause in North America by a founder-effect mutation.

Qualitative dermatoglyphic traits in brachial plexus palsy.

It has been considered for many years that the cause of perinatal brachial plexus palsy (PBPP) is excessive lateral traction applied to the fetal head at delivery, in association with anterior shoulder dystocia, but this do not explain all cases of brachial plexus palsy. The incidence found in several family members could be suggestive for inheritance with variable expression. The aim of this study was to prove early found confirmations of genetic predisposition for PBPP In the previous studies, the quantitative dermatoglyphic analysis showed some differences in digito-palmar dermatoglyphs between patients with PBPP and healthy controls. Now this qualitative analysis will try to determine hereditary of those diseases. We analyzed digito-palmar dermatoglyphics from 140 subjects (70 males and 70 females) diagnosed with PBPP and 400 phenotypically healthy adults (200 males and 200 females) from Zagreb area as control group. The results of Chi-square test showed statistically significant differences for frequencies of patterns on fingers in females between the groups observed. Statistically significant differences were found on palms in III and IV interdigital areas in both males and females and in thenar and I interdigital area only in females. As it was found in previous researches on quantitative dermatoglyphic traits, more differences are found between females with PBPP and control group, than between males. The fact, that the main presumed cause of PBPP is obstetrical trauma, it could be associated with congenital variability in formation of brachial plexus.

Dermatoglyphs and brachial plexus palsy.

Perinatal brachial plexus palsy (PBPP) is a handicap quite commonly encountered in daily routine. Although birth trauma is considered to be the major cause of the defect, it has been observed that PBPP occurs only in some infants born under identical or nearly identical conditions. The aim of this study was to test the hypothesis of genetic predisposition for PBPP. It is well known that digito-palmar dermatoglyphs can be used to determine hereditary roots of some diseases. Thus, we found it meaningful to do a study analysis of digito-palmar dermatoglyphs in this disease as well, conducting it on 140 subjects (70 males and 70 females) diagnosed with PBPP. The control group was composed of fingerprints obtained from 400 adult and phenotypically healthy subjects (200 males and 200 females) from the Zagreb area. The results of multivariate and univariate analysis of variance have shown statistically significant differences between the groups observed. In spite of lower percentage of accurately classified female subjects by discriminant analysis, the results of quantitative analysis of digito-palmar dermatoglyphs appeared to suggest a genetic predisposition for the occurrence of PBPP.

Desmoid-type fibromatoses involving the brachial plexus: treatment options and assessment of c-KIT mutational status.

OBJECT: Desmoid-type fibromatoses are a locally invasive soft-tissue lesion that is most commonly encountered in abdominal sites. The tumor also affects head and neck areas, particularly the supraclavicular region, where it may encase and distort the brachial plexus and compromise neurovascular structures. Neurosurgeons may be called on to treat desmoid-type fibromatoses in these sites. The authors describe their experience in treating four patients with desmoid-type fibromatoses involving the brachial plexus and report the results of immunohistochemical analysis of the tumors. METHODS: Gross-total excision with nerve sparing was the first-line therapy of choice, although the surgery was challenging. Intraoperative identification of the site of tumor origin from musculoaponeurotic tissues by the neurosurgeon was necessary in two of the four cases to achieve a correct frozen section or final pathological diagnosis. Immunostaining for c-KIT (CD117) was undertaken in all cases in light of a previous report of positive CD117 immunoreactivity in abdominal desmoid-type fibromatoses. All four tumors manifested weak focal immunostaining for c-KIT. One of the patients was given adjuvant imatinib mesylate therapy, with limited success. Subsequent polymerase chain reaction testing revealed that three of the four tumors manifested a single base pair change in exon 10 of the c-KIT gene (A to C in two cases and A to G in one case). There was local recurrence in three patients, despite gross-total excision. With the combination of surgery and radiation therapy, local disease control was achieved in three of the four patients. CONCLUSIONS: This represents the first report of c-KIT sequencing in desmoid-type fibromatoses and suggests a possible biological basis for continuing to explore the use of adjuvant imatinib mesylate therapy.

Inflammation and neuropathic attacks in hereditary brachial plexus neuropathy.

OBJECTIVE: To study the role of mechanical, infectious, and inflammatory factors inducing neuropathic attacks in hereditary brachial plexus neuropathy (HBPN), an autosomal dominant disorder characterised by attacks of pain and weakness, atrophy, and sensory alterations of the shoulder girdle and upper limb muscles. METHODS: Four patients from separate kindreds with HBPN were evaluated. Upper extremity nerve biopsies were obtained during attacks from a person of each kindred. In situ hybridisation for common viruses in nerve tissue and genetic testing for a hereditary tendency to pressure palsies (HNPP; tomaculous neuropathy) were undertaken. Two patients treated with intravenous methyl prednisolone had serial clinical and electrophysiological examinations. One patient was followed prospectively through pregnancy and during the development of a stereotypic attack after elective caesarean delivery. RESULTS: Upper extremity nerve biopsies in two patients showed prominent perivascular inflammatory infiltrates with vessel wall disruption. Nerve in situ hybridisation for viruses was negative. There were no tomaculous nerve changes. In two patients intravenous methyl prednisolone ameliorated symptoms (largely pain), but with tapering of steroid dose, signs and symptoms worsened. Elective caesarean delivery did not prevent a typical postpartum attack. CONCLUSIONS: Inflammation, probably immune, appears pathogenic for some if not all attacks of HBPN. Immune modulation may be useful in preventing or reducing the neuropathic attacks, although controlled trials are needed to establish efficacy, as correction of the mutant gene is still not possible. The genes involved in immune regulation may be candidates for causing HBPN disorders.

Unusual clinical presentations in patients harboring the facioscapulohumeral dystrophy 4q35 deletion.

Facioscapulohumeral dystrophy (FSHD) is a dominantly inherited myopathy usually associated with a deletion at locus 4q35. Typically, FSHD patients present with a recognizable constellation of signs including weakness of facial, shoulder and pelvic girdle, humeral, and anterior foreleg muscles; preservation of some muscles including the deltoids; and other characteristic features including prominent scapular winging, anterior axillary folds, and horizontally positioned clavicles. We performed clinical and FSHD genetic studies on four patients with atypical clinical features who were cared for at a regional neuromuscular center. The four patients, each harboring 4q35 deletions, presented with atypical phenotypes including facial-sparing scapular myopathy, limb-girdle muscular dystrophy, distal myopathy, and asymmetric brachial weakness. This report demonstrates the expanding clinical heterogeneity in patients harboring the 4q35 deletion.

Lesion of the anterior branch of axillary nerve in a patient with hereditary neuropathy with liability to pressure palsies.

We report the case of a 30-year-old woman affected by hereditary neuropathy with liability to pressure palsies (HNPP), who developed a painless left axillary neuropathy after sleeping on her left side, on a firm orthopaedic mattress, in her eighth month of pregnancy. Electromyography (EMG) showing neurogenic signs in the left anterior and middle deltoid, and normal findings in the left teres minor, posterior deltoid and other proximal upper limb muscles, demonstrated that the lesion was at the level of the axillary anterior branch. A direct compression of this branch against the surgical neck of the humerus seems the most likely pathogenic mechanism. This is the first documented description of an axillary neuropathy in HNPP. Knowledge of its possible occurrence may be important for prevention purposes.