Neuroblastoma with symptomatic epidural compression in the infant: the AIEOP experience.

BACKGROUND: Symptoms of epidural compression (SEC) in children with neuroblastoma (particularly infants) may be misinterpreted, leading to delay in diagnosis. PATIENTS AND METHODS: Clinical, imaging and follow-up data of 34 infants with neuroblastoma and SEC diagnosed between 2000 and 2011 at Italian AIEOP centers were retrieved and reviewed. RESULTS: Median age at initial SEC was 104 days (IQR 47-234). Main symptoms included motor deficit (85.3%), pain (38.2%), bladder and bowel dysfunctions (20.6% each). In the symptom-diagnosis interval (S-DI) (median, 12 days; IQR 7-34), the frequency of grade 3 motor deficit increased from 11.8% to 44.1% and that of bladder dysfunction from 20.6% to 32.4%. S-DI was significantly longer (P = 0.011) for patients developing grade 3 motor deficit. First treatment of SEC was neurosurgery in 14 patients, and chemotherapy in 20. SEC regressed in 11 patients (32.3%), improved in 9 (26.5%), and remained stable in 14 (41.2%), without treatment-related differences. Median follow-up was 82 months. At last visit, 11 patients (32.3%) were sequelae-free while 23 (67.7%) had sequelae, including motor deficit (55.9%), bladder (50.0%) and bowel dysfunctions (28.4%), and spinal abnormalities (38.2%). Sequelae were rated severe in 50% of patients. Severe sequelae scores were more frequent in patients presenting with spinal canal invasion >66% (P = 0.039) and grade 3 motor deficit (P = 0.084). CONCLUSIONS: Both neurosurgery and chemotherapy provide unsatisfactory results once paraplegia has been established. Sequelae developed in the majority of study patients and were severe in a half of them. Greater awareness by parents and physicians regarding SEC is warranted.

[Detection of oculomotor nerve compression by 3D-FIESTA MRI in a patient with pituitary apoplexy and diabetes mellitus].

We report the usefulness of 3D-FIESTA magnetic resonance imaging(MRI)for the detection of oculomotor nerve palsy in a case of pituitary apoplexy. A 69-year-old man with diabetes mellitus presented with complete left-side blepharoptosis. Computed tomography of the brain showed an intrasellar mass with hemorrhage. MRI demonstrated a pituitary adenoma with a cyst toward the left cavernous sinus, which was diagnosed as pituitary apoplexy. 3D-FIESTA revealed that the left oculomotor nerve was compressed by the cyst. He underwent trans-sphenoid tumor resection at 5 days after his hospitalization. Post-operative 3D-FIESTA MRI revealed decrease in compression of the left oculomotor nerve by the cyst. His left oculomotor palsy recovered completely within a few months. Oculomotor nerve palsy can occur due to various diseases, and 3D-FIESTA MRI is useful for detection of oculomotor nerve compression, especially in the field of parasellar lesions.

[Hereditary sensory and motor neuropathy and hereditary sensory and autonomic neuropathies: recent advances]. / Nouveautés dans les maladies de Charcot-Marie-Tooth et les neuropathies sensitives et dysautonomiques héréditaires.

This review summarizes the recent genetic advances in hereditary sensorimotor neuropathy also called Charcot-Marie-Tooth disease. The different new genes discovered in 2010 and their underlying phenotypes will be presented.

Lipomas of the Brachial Plexus: A Case Series and Review of the Literature.

BACKGROUND: Lipomas are common benign tumors. When they develop in proximity to peripheral nerves, they can cause neurologic symptoms secondary to mass effect. Previous reports have shown symptom resolution after removal of lipomas compressing various upper extremity peripheral nerves. However, brachial plexus lipomas are relatively rare. Our multidisciplinary experience with brachial plexus lipoma resection is reviewed in the largest case series to date. METHODS: A retrospective chart review of all patients undergoing resection of brachial plexus lipomatous tumors between 2006 and 2016 was performed. Patient demographic data, diagnostic imaging, clinical presentation, operative details, surgical pathology, and clinical outcomes were reviewed. RESULTS: Twelve brachial plexus lipomatous tumors were resected in 11 patients: 10 lipomas, 1 hibernoma, and 1 atypical lipomatous tumor. The most common tumor location was supraclavicular (50%), followed by axillary (42%), and proximal medial arm (8%). The most common brachial plexus segment involved was the upper trunk (50%), followed by posterior cord (25%), lateral pectoral nerve (8%), lower trunk (8%), and proximal median nerve (8%). Most patients presented with an enlarging painless mass (58%). Of the patients who presented with neurologic symptoms, symptoms resolved in the majority (80%). CONCLUSIONS: Brachial plexus lipomas are rare causes of compression neuropathy in the upper extremity. Careful resection and knowledge of brachial plexus anatomy, which may be distorted by the tumor, are critical to achieving a successful surgical outcome with predictable symptom resolution. Finally, surveillance magnetic resonance imaging may be warranted for atypical lesions.

[Ma2 antibody and multiple mononeuropathies]. / Mononeuropathie multiple et anticorps anti-Ma2.

Anti-Ma2 antibodies belong to a family of onconeuronal antibodies that target proteins expressed in brain, testis and several tumors. Previously observed in patients presenting with limbic encephalitis, they seem to be associated with several other paraneoplastic syndromes. We report the case of a 73-year-old woman presenting sensory and motor neuropathy associated with non-small-cell lung cancer who had Ma2-antibodies.

Compression neuropathy of common peroneal nerve caused by a popliteal cyst: A case report.

RATIONALE: Popliteal cyst developing in the sheath of a peripheral nerve or joint capsule may cause compression neuropathy. Although popliteal cyst is very common lesion, it seldom causes serious complications. Common peroneal nerve compression is rarely caused by an extraneural popliteal cyst. PATIENT CONCERNS: We presented the case of a 52-year-old female with common peroneal nerve compression caused by an extraneural popliteal cyst. DIAGNOSES: Electromyography showed the damage of common peroneal nerve. MRI magnetic resonance imaging showed the lump to be a popliteal cyst. She was diagnosed as peroneal nerve injury and popliteal cyst. INTERVENTIONS: The patient was performed peroneal nerve decompression and popliteal cyst excision surgery. We excised the cyst completely and soluted the common peroneal nerve thoroughly. The cyst was filled with thick mucinous material. OUTCOMES: The pathological report showed that the excised mass was a popliteal cyst. There were no postoperative complications. Pain and hypoesthesia resolved 6 months after surgery. LESSONS: In this case, compression of the common peroneal nerve was due to an extraneural popliteal cyst, a situation rarely encountered. MRI can show in better detail their size and internal contents as well as their relation with surrounding anatomic structures. Patients with nerve entrapment caused by enlarged or ruptured cysts must be microsurgically excised if symptomatic.

Abnormal small heat shock protein interactions involving neuropathy-associated HSP22 (HSPB8) mutants.

Two mutations (K141E, K141N) in the small heat shock protein (sHSP) HSP22 (HSPB8) are associated with the inherited peripheral motor neuron disorders distal hereditary motor neuropathy type II and axonal Charcot-Marie-Tooth disease type 2L. HSP22 is known to form homodimers, heterodimers with other sHSPs, and larger oligomers. In an effort to elucidate the cellular basis for these diseases, we have determined the ability of mutant HSP22 to interact with itself, with wild-type HSP22, and with other sHSPs that are abundant in neurons. Using the yeast two-hybrid method, quantitative fluorescence resonance energy transfer in live cells, and cross-linking, we found aberrantly increased interactions of mutant HSP22 forms with themselves, with wild-type HSP22, and with the other sHSPs, alphaB-crystallin, and HSP27. Interaction with HSP20 was not affected by the mutations. The data suggest that each mutant form of HSP22 has a characteristic pattern of abnormal interaction properties. A mutation (S135F) in HSP27 that is also associated with these disorders showed increased interaction with wild-type HSP22 also, suggesting linkage of these two etiologic factors, HSP22 and HSP27, into one common pathway. Increased interactions involving mutant sHSPs may be the molecular basis for their increased tendency to form cytoplasmic protein aggregates, and for the occurrence of the associated neuropathies.

Prevalence of thoracic spine lesions masquerading as cauda equina syndrome: yield of a novel magnetic resonance imaging protocol.

Our objective was to describe the yield of actionable thoracic spine lesions for a novel magnetic resonance imaging (MRI) protocol including evaluation of the thoracic spine among patients presenting to the Emergency Department (ED) with symptoms consistent with epidural compression syndrome. Our ED and Department of Radiology together designed a novel rapid MRI protocol entailing 3D volumetric T2 weighted sequences through both the thoracic and lumbar spine obtained in the sagittal plane to assess for both lumbar and thoracic spine lesions. We recorded study outcomes for all patients undergoing this protocol or conventional lumbar MRI during May 2014-May 2015 to determine the prevalence of actionable thoracic spine lesions. We defined an actionable thoracic lesion as any pathology requiring treatment (e.g., medication, admission, surgery) not otherwise indicated on the basis of lumbar spine findings. During the study period, 112 of 124 (90.3%) of ED patients undergoing MRI evaluation for epidural compression syndrome underwent the novel protocol. The remaining patients underwent evaluation of the lumbar spine using only a conventional MRI protocol. Of the 112 patients undergoing the novel protocol, 6 (5.4%) patients had thoracic spine lesions indicating therapy not otherwise indicated by lumbar spine findings. The etiologies of these six lesions were: neoplasms (2), de-myelination (2), compression fracture (1), and degeneration due to pernicious anemia (1). Emergency providers should strongly consider the routine use of MRI protocols including thoracic spine evaluation in patients presenting to the ED with symptoms consistent with epidural compression syndrome.

Phenotype HNPP (Hereditary Neuropathy With Liability to Pressure Palsies) Induced by Medical Procedures.

The phenotype HNPP (hereditary neuropathy with liability to pressure palsies) is caused by heterozygous deletion of the PMP22 gene. HNPP is clinically characterized by asymmetric focal sensory loss and muscle weakness. Reports of HNPP have been rare. In this article, we report the case of an asymptomatic woman with the HNPP mutation. After undergoing total knee arthroplasty, she developed a footdrop with prolonged recovery. We concluded (a) that the HNPP mutation may carry a high risk for certain surgical procedures not expected to cause neurologic deficits in normal patients and (b) that humans with the HNPP mutation can be asymptomatic. Lack of symptoms can contribute to underrecognition of the disease.

Effect of Intrathecal Baclofen on Delayed-Onset Paroxysmal Dystonia due to Compression Injury Resulting From Congenital and Progressive Spinal Bone Deformities in Chondrodysplasia Punctata.

BACKGROUND: Dystonia due to spinal lesions in adult patients is characterized by the provocation and/or amelioration of the spasm by somatosensory stimulation with a sensory trick. PATIENT DESCRIPTION: An infant with brachytelephalangic chondrodysplasia punctata developed flaccid tetraplegia due to cervical cord compression resulting from congenital atlantoaxial dislocation. Episodic, tonic extension of the extremities, neck, and trunk had appeared daily since age two years and was often provoked by tactile stimulation. Although decompression surgery was performed at age three years, progressive spinal deformity resulted in the aggravation of episodic dystonia thereafter, lasting for hours. Foot dorsiflexion and wearing a truncal brace for scoliosis inhibited these spasms. Intrathecal baclofen bolus injection transiently ameliorated the paroxysmal dystonia and detrusor-sphincter dyssynergia in the lower urinary tract. CONCLUSION: Paroxysmal dystonia is unusual in children with spinal cord lesions; however, it should be recognized for appropriate individualized clinical management.

Exclusion of the ninjurin gene as a candidate for hereditary sensory neuropathies type I and type II.

Ninjurin is a protein that is up-regulated in Schwann cells and neurons after peripheral nerve injury. Its role in promoting nerve regeneration and its expression in sensory neurons of dorsal root ganglia, as well as the chromosomal localization of the ninjurin gene, makes this gene a candidate for hereditary sensory neuropathies (HSN). In the present report, the human ninjurin gene was analyzed in 17 unrelated patients with HSN type I, two patients with HSN type II, and 10 normal controls, by single strand conformation polymorphism and by direct sequencing. All three exons and splice junctions of the gene were investigated and no mutations were found in our sample of patients. Our results rule out a mutation in the translated region of the ninjurin gene as a cause of HSN type I and type II.

Congenital neuropathy with the absence of large myelinated fibers.

Twelve patients with hereditary motor and sensory neuropathy with the absence of large myelinated fibers have been reported. All of these patients had central nervous system involvement. In this report, we describe the first patient with pure motor and sensory neuropathy with the absence of large myelinated fibers without central nervous system involvement. Morphometric analysis of the biopsied sural nerve specimen revealed extremely small myelinated fibers compared with previously reported patients. It is supposed that the cause of this disease might be the abnormal development of axons of the peripheral nerves.

[X-ray computed tomography of lumbosacral roots and primary hypertrophic neuritis (Dejerine-Sottas disease)]. / Scanner X des racines lombo-sacrées et névrite hypertrophique primitive (maladie de Dejerine-Sottas).

CT without contrast of lumbosacral nerve roots was performed in 13 patients with peroneal atrophy and 28 control subjects. Two series of 5 mm serial sections parallel to the plane of the disk were examined at the L4-L5 and L5-S1 levels, and the transverse diameter of the S1 nerve roots measured at the lower part of the lateral recess. Results showed frank bilateral, grossly symmetrical hypertrophy of lumbosacral roots in 8 of the 13 patients. This hypertrophy involved all roots examined (L4, L5, S1), except in one case where only S1 roots were involved. Hypertrophy was often more marked on the distal part of the roots and on spinal nerves, contrasting with the sometimes normal or only slightly altered appearance of the nerve roots emerging from the dural sac. In these 8 cases, the diameter of the S1 nerve roots was 8 to 18 mm, in contrast to a mean of 3.5 +/- 1 mm in the 28 controls. CT scan images were normal in the remaining 5 patients. The presence of a CT image of nerve hypertrophy was in all cases associated with a marked fall in nerve conduction rate (median nerve motor conduction rate less than 25 msec-1), and a decrease in number of myelinated fibers with numerous onion bulbs. In contrast, the absence of CT nerve hypertrophy could not predict the results of electrophysiological and histological examinations.

[A case of motor and sensory polyneuropathy with retinitis pigmentosa and diffuse idiopathic skeletal hyperostosis].

We here report a 53-year-old man who presented with motor and sensory polyneuropathy, retinitis pigmentosa and diffuse idiopathic skeletal hyperostosis (DISH). He had a 15-year history of diabetes mellitus (DM). Visual impairment appeared at 17 years of age. Since age 47, he showed a slowly progressive sensory impairment and muscle weakness of the extremities. On neurological examination, retinitis pigmentosa and severe muscle atrophy, muscle weakness and sensory disturbance of all modalities in the distal portions of all four extremities were observed. Deep tendon reflexes were absent. A plain X-P showed diffuse ossification of the spinal and extraspinal ligaments. The motor nerve conduction velocities were severely reduced and no sensory nerve action potentials were evoked. The CSF examination revealed an increased protein level without pleocytosis. The sural nerve biopsy showed a marked onion bulb formation and a loss of the myelinated nerve fibers, which could not be solely explained by DM. As the phytanic acids levels, beta-lipoprotein, lactate and pyruvate in the sera were within the normal ranges, Refsum disease, Bassen-Kornzweig syndrome and mitochondrial diseases were unlikely in this patient. The presence of demyelinating and axonal polyneuropathy in this patient may have been caused by a common metabolic disturbance which produced both retinitis pigmentosa and DISH.

Proximal dominant hereditary motor and sensory neuropathy with proximal dominance association with mutation in the TRK-fused gene.

IMPORTANCE: Hereditary motor and sensory neuropathy with proximal dominance (HMSN-P) has been reported as a rare type of autosomal dominant adult-onset Charcot-Marie-Tooth disease. HMSN-P has been described only in Japanese descendants since 1997, and the causative gene has not been found. OBJECTIVES: To identify the genetic cause of HMSN-P in a Korean family and determine the pathogenic mechanism. DESIGN: Genetic and observational analysis. SETTING: Translational research center for rare neurologic disease. PARTICIPANTS: Twenty-eight individuals (12 men and 16 women) from a Korean family with HMSN-P. MAIN OUTCOME MEASURES: Whole-exome sequencing, linkage analysis, and magnetic resonance imaging. RESULTS: Through whole-exome sequencing, we revealed that HMSN-P is caused by a mutation in the TRK-fused gene (TFG). Clinical heterogeneities were revealed in HMSN-P between Korean and Japanese patients. The patients in the present report showed faster progression of the disease compared with the Japanese patients, and sensory nerve action potentials of the sural nerve were lost in the early stages of the disease. Moreover, tremor and hyperlipidemia were frequently found. Magnetic resonance imaging of the lower extremity revealed a distinct proximal dominant and sequential pattern of muscular involvement with a clearly different pattern than patients with Charcot-Marie-Tooth disease type 1A. Particularly, endoneural blood vessels revealed marked narrowing of the lumen with swollen vesicular endothelial cells. CONCLUSIONS AND RELEVANCE: The underlying cause of HMSN-P proves to be a mutation in TFG that lies on chromosome 3q13.2. This disease is not limited to Japanese descendants, and marked narrowing of endoneural blood vessels was noted in the present study. We believe that TFG can affect the peripheral nerve tissue.

Proximal median nerve entrapment caused by a distal biceps tendon cyst: an ultrasonographic diagnosis.

A 60-yr-old woman reported severe pain in the proximal part of her left forearm. The pain was also radiating toward the median nerve-innervated areas of the arm, especially during elbow flexion. Ultrasonographic imaging showed a well defined ganglion cyst around the distal biceps tendon close to the median nerve. Under ultrasound guidance, the cyst was aspirated and corticosteroid injection was performed. The patient's complaint improved 1 wk after the injection, and she started to flex her elbow without any pain. This case highlights the role of ultrasonography as a useful adjunctive tool not only to morphologically confirm a peripheral nerve entrapment but also to uncover the possible underlying etiology and to guide precisely during an intervention.

Small-fiber neuropathy in patients with ALS.

OBJECTIVE: To investigate the involvement of the epidermal small sensory fibers in the neurodegenerative process in amyotrophic lateral sclerosis (ALS). METHODS: In the present study, skin biopsies of 28 patients with ALS were obtained at an average of 34 months after disease onset by history. Protein gene product 9.5 (PGP9.5) immunohistochemistry findings were compared to 17 age-matched controls. The primary endpoint of the study was to evaluate the decrease in the density of small intraepidermal nerve fibers and to compare the prevalence of small-fiber neuropathy in patients with ALS and in controls. RESULTS: We found a significant reduction in epidermal nerve fiber density in the distal calf of patients with ALS (4.8 ± 3.7 fibers/mm vs 12.2 ± 4.6 in age-matched controls, p<0.0001). The extent of fiber loss was age-dependent. Also, the number of subjects with small-fiber neuropathy was significantly higher in the ALS group than in the controls (79% vs 12%). Correspondingly, mild sensory symptoms including diffuse dysesthesias, paresthesias, and hypesthesia were found in 7 patients. In 17 biopsies of patients with ALS, but only in 2 controls, we saw larger (>1.5 µm in diameter) focal swellings of epidermal axons resembling spheroids, suggesting trafficking defects. CONCLUSIONS: These results indicate that small, distal epidermal nerve fibers are involved in this disease, supporting the concept of distal axonopathy in ALS.