New structural variations responsible for Charcot-Marie-Tooth disease: The first two large KIF5A deletions detected by CovCopCan software.

Next-generation sequencing (NGS) allows the detection of mutations in inherited genetic diseases, like the Charcot-Marie-Tooth disease (CMT) which is the most common hereditary peripheral neuropathy. The majority of mutations detected by NGS are single nucleotide variants (SNVs) or small indels, while structural variants (SVs) are often underdiagnosed. PMP22 was the first gene described as being involved in CMT via a SV of duplication type. To date, more than 90 genes are known to be involved in CMT, with mainly SNVs and short indels described. Herein targeted NGS and the CovCopCan bioinformatic tool were used in two unrelated families, both presenting with typical CMT symptoms with pyramidal involvement. We have discovered two large SVs in KIF5A, a gene known to cause axonal forms of CMT (CMT2) in which no SVs have yet been described. In the first family, the patient presented with a large deletion of 12 kb in KIF5A from Chr12:57,956,278 to Chr12:57,968,335 including exons 2-15, that could lead to mutation c.(130-943_c.1717-533del), p.(Gly44_Leu572del). In the second family, two cases presented with a large deletion of 3 kb in KIF5A from Chr12:57,974,133 to Chr12:57,977,210 including exons 24-28, that could lead to mutation c.(2539-605_*36 + 211del), p.(Leu847_Ser1032delins33). In addition, bioinformatic sequence analysis revealed that a NAHR (Non-Allelic-Homologous-Recombination) mechanism, such as those in the PMP22 duplication, could be responsible for one of the KIF5A SVs and could potentially be present in a number of other patients. This study reveals that large KIF5A deletions can cause CMT2 and highlights the importance of analyzing not only the SNVs but also the SVs during diagnosis of neuropathies.

Correction of thoracic adolescent idiopathic scoliosis via a direct convex rod manoeuvre.

The various techniques available for scoliosis surgery via the posterior approach involve positioning implants on either side of the curve and reducing the deformity by manoeuvres on the concave rod or simultaneously on both rods. Correction solely via a direct convex rod manoeuvre would eliminate the need for implants on the concave side. This technique was used to treat thoracic adolescent idiopathic scoliosis in 23 patients with a mean age of 14 years and 9 months. Low-dose biplanar EOS radiographs were obtained before surgery, on post-operative day 7, and at last follow-up (at least 2 years after surgery) to allow comparisons of Cobb's angle (72°, 33°, and 35°, respectively), thoracic kyphosis (21°, 29°, and 26°), lumbar lordosis (58°, 50°, and 55°), and apical vertebra rotation (-26°,-12°, and-11°). Although scoliosis requires corrections in all three dimensions, this technique seems to produce satisfactory outcomes while obviating the need for implants on the concave side, thereby decreasing the risk of iatrogenic adverse events. LEVEL OF EVIDENCE: IV.

Reversible lesions of the corpus callosum with initially restricted diffusion in a series of Caucasian children.

BACKGROUND: Reversible lesions of the corpus callosum with initial restricted diffusion on diffusion-weighted imaging (DWI) are rare and mainly described in the south Asiatic population. OBJECTIVE: The purpose of this study was to describe the clinical presentation, imaging findings, prognosis and etiology of transient restricted diffusion lesions of the corpus callosum in a series of Caucasian children. MATERIALS AND METHODS: Seven children presenting with a transient restricted DWI lesion of the corpus callosum were included. Their clinical presentations and paraclinical examinations were investigated in addition to their MRI findings during the acute phase and at follow-up. RESULTS: Five patients initially presenting with prodromal flu-like symptoms were diagnosed with mild encephalopathy with reversible corpus callosum lesions, three of which were due to the influenza virus. For two patients (twins) with a stroke-like presentation and without febrile illness, a central nervous system manifestation of X-linked Charcot-Marie-Tooth disease with connexin 32 mutation was diagnosed. All patients had a good clinical prognosis without clinical sequelae or residual MRI lesion for all patients at follow-up. CONCLUSION: A transient lesion of the corpus callosum with restricted diffusion should prompt the radiologist to suggest an infectious trigger in children. The prognosis of these patients was good with normalization of clinical symptoms and MRI without any specific treatment.

Magnetic resonance imaging in children presenting migraine with aura: Association of hypoperfusion detected by arterial spin labelling and vasospasm on MR angiography findings.

Objective A child presenting with a first attack of migraine with aura usually undergoes magnetic resonance imaging (MRI) to rule out stroke. The purpose of this study was to report vascular and brain perfusion findings in children suffering from migraine with aura on time-of-flight MR angiography (TOF-MRA) and MR perfusion imaging using arterial spin labelling (ASL). Methods We retrospectively included all children who had undergone an emergency MRI examination with ASL and TOF-MRA sequences for acute neurological deficit and were given a final diagnosis of migraine with aura. The ASL perfusion maps and TOF-MRA images were independently assessed by reviewers blinded to clinical data. A mean cerebral blood flow (CBF) value was obtained for each cerebral lobe after automatic data post-processing. Results Seventeen children were finally included. Hypoperfusion was identified in one or more cerebral lobes on ASL perfusion maps by visual assessment in 16/17 (94%) children. Vasospasm was noted within the intracranial vasculature on the TOF-MRA images in 12/17 (71%) children. All (100%) of the abnormal TOF-MRA images were associated with homolateral hypoperfusion. Mean CBF values were significantly lower ( P < 0.05) in visually hypoperfused lobes than in normally perfused lobes. Conclusion ASL and TOF-MRA are two totally non-invasive, easy-to-use MRI sequences for children in emergency settings. Hypoperfusion associated with homolateral vasospasm may suggest a diagnosis of migraine with aura.

Validity and utility of monopolar spinal cord stimulation in pediatric scoliosis surgery.

PURPOSE: To assess the validity and utility of monopolar stimulation (between a peridural needle and a large adhesive anode placed in the sternal area) for intraoperative monitoring in scoliosis surgery. METHODS: This procedure was assessed during 41 operations involving either arthrodesis with posterior instrumentation or a Vertical Expandable Prosthetic Titanium Rib (VEPTR). Responses evoked by monopolar stimulation were compared with those evoked by bipolar stimulation between two epidural needle electrodes. Potentials evoked by monopolar stimulation in the upper limbs were compared with those evoked in the lower limbs during the same stimulation procedure. RESULTS: Monopolar stimulation yielded equivalent and, if anything, more stable responses in the lower limbs. Recording in the upper limbs was satisfactory and allowed a decrease in responses to be detected in two patients. Acceptable thresholds for changes in amplitude relative to baseline were 40 % for upper limbs and 30 % for lower limbs. CONCLUSIONS: Monopolar stimulation can be used to monitor the spinal cord during surgery for scoliosis correction. This procedure is more convenient for the surgeon and allows for the combined recording of responses in all four limbs, which can be useful in the case of surgical techniques such as those involving a VEPTR.

A case of cutaneous sensory neuropathy associated with Churg-Strauss syndrome.

Cutaneous sensory neuropathy manifests as multiple, sharply demarcated areas of hypoesthesia with a variable degree of pain. This rare neuropathy is caused by a multifocal infection or inflammation of the small sensory nerves of the skin. We report a case in a patient with febrile arthritis and eosinophilia. Her chronic cough and the presence of extravascular infiltrates of eosinophils in a neuromuscular biopsy specimen suggested Churg-Strauss syndrome. The course was favorable under corticosteroid therapy.