Outcome following Nerve Repair of High Isolated Clean Sharp Injuries of the Ulnar Nerve

Objective

The detailed outcome of surgical repair of high isolated clean sharp (HICS) ulnar nerve lesions has become relevant in view of the recent development of distal nerve transfer. Our goal was to determine the outcome of HICS ulnar nerve repair in order to create a basis for the optimal management of these lesions.

Methods

High ulnar nerve lesions are defined as localized in the area ranging from the proximal forearm to the axilla just distal to the branching of the medial cord of the brachial plexus. A meta-analysis of the literature concerning high ulnar nerve injuries was performed. Additionally, a retrospective study of the outcome of nerve repair of HICS ulnar nerve injuries at our institution was performed. The Rotterdam Intrinsic Hand Myometer and the Rosén-Lundborg protocol were used.

Results

The literature review identified 46 papers. Many articles presented outcomes of mixed lesion groups consisting of combined ulnar and median nerves, or the outcome of high and low level injuries was pooled. In addition, outcome was expressed using different scoring systems. 40 patients with HICS ulnar nerve lesions were found with sufficient data for further analysis. In our institution, 15 patients had nerve repair with a median interval between trauma and reconstruction of 17 days (range 0–516). The mean score of the motor and sensory domain of the Rosen''s Scale instrument was 58% and 38% of the unaffected arm, respectively. Two-point discrimination never reached less then 12 mm.

Conclusion

From the literature, it was not possible to draw a definitive conclusion on outcome of surgical repair of HICS ulnar nerve lesions. Detailed neurological function assessment of our own patients showed that some ulnar nerve function returned. Intrinsic muscle strength recovery was generally poor. Based on this study, one might cautiously argue that repair strategies of HICS ulnar nerve lesions need to be improved.     

Surgical Decompression of Painful Diabetic Peripheral Neuropathy: The Role of Pain Distribution

Objective

To investigate the effect of surgical decompression on painful diabetic peripheral neuropathy (DPN) patients and discuss the role which pain distribution and characterization play in the management of painful DPN as well as the underlying mechanism involved.

Methods

A total of 306 patients with painful diabetic lower-extremity neuropathy were treated with Dellon surgical nerve decompression in our department. Clinical evaluation including Visual analogue scale (VAS), Brief Pain Inventory Short Form for diabetic peripheral neuropathy (BPI-DPN) questionnaire, two-point discrimination (2-PD), nerve conduction velocity (NCV) and high-resolution ultrasonography (cross-sectional area, CSA) were performed in all cases preoperatively, and at 6 month intervals for 2 years post-decompression. The patients who underwent surgery were retrospectively assigned into two subgroups (focal and diffuse pain) according to the distribution of the diabetic neuropathic pain. The control group included 92 painful DPN patients without surgery.

Results

The levels of VAS, scores in BPI-DPN, 2-PD, NCV results and CSA were all improved in surgical group when compared to the control group (P<0.05). More improvement of VAS, scores in BPI-DPN and CSA was observed in focal pain group than that in diffuse group (P<0.05).

Conclusions

Efficacy of decompression of multiple lower-extremity peripheral nerves in patients with painful diabetic neuropathy was confirmed in this study. While both focal and diffuse group could benefit from surgical decompression, pain relief and morphological restoration could be better achieved in focal group.     

T2-Signal of Ulnar Nerve Branches at the Wrist in Guyon’s Canal Syndrome

Objective

To evaluate T2-signal of high-resolution MRI in distal ulnar nerve branches at the wrist as diagnostic sign of guyon’s-canal-syndrome (GCS).

Materials and Methods

11 GCS patients confirmed by clinical/electrophysiological findings, and 20 wrists from 11 asymptomatic volunteers were prospectively included to undergo the following protocol: axial T2-weighted-fat-suppressed and T1-weighted-turbo-spin-echo-sequences (3T-MR-scanner, Magnetom/Verio/Siemens). Patients were examined in prone position with the arm extended and wrist placed in an 8-channel surface-array-coil. Nerve T2-signal was evaluated as contrast-to-noise-ratios (CNR) from proximal-to-distal in ulnar nerve trunk, its superficial/sensory and deep/motor branch. Distal motor-nerve-conduction (distal-motor-latency (dml)) to first dorsal-interosseus (IOD I) and abductor digiti minimi muscles was correlated with T2-signal. Approval by the institutional review-board and written informed consent was given by all participants.

Results

In GCS, mean nerve T2-signal was strongly increased within the deep/motor branch (11.7±4.8 vs.controls:−5.3±2.4;p = 0.001) but clearly less and not significantly increased in ulnar nerve trunk (6.8±6.4vs.−7.4±2.5;p = 0.07) and superficial/sensory branch (−2.1±4.9vs.−9.7±2.9;p = 0.08). Median nerve T2-signal did not differ between patients and controls (−9.8±2.5vs.−6.7±4.2;p = 0.45). T2-signal of deep/motor branch correlated strongly with motor-conduction-velocity to IOD I in non-linear fashion (R² = −0.8;p<0.001). ROC-analysis revealed increased nerve T2-signal of the deep/motor branch to be a sign of excellent diagnostic performance (area-under-the-curve 0.94, 95% CI: 0.85–1.00; specificity 90%, sensitivity 89.5%).

Conclusions

Nerve T2-signal increase of distal ulnar nerve branches and in particular of the deep/motor branch is highly accurate for the diagnostic determination of GCS. Furthermore, for the first time it was found in nerve entrapment injury that T2-signal strongly correlates with electrical-conduction-velocity.     

Elbow Flexion Contractures in Childhood in Obstetric Brachial Plexus Lesions: A Longitudinal Study of 20 Neurosurgically Reconstructed Infants with 8-Year Follow-up

Objective

 Little knowledge exists on the development of elbow flexion contractures in children with obstetrical brachial plexus lesion (OBPL). This study aims to evaluate the prognostic significance of several neuromuscular parameters in infants with OBPL regarding the later development of elbow flexion contractures.

Methods

 Twenty infants with OBPL with insufficient signs of recovery in the first months of life who were neurosurgically reconstructed were included. At a mean age of 4.6 months, the following neuromuscular parameters were assessed: existence of flexion contractures, cross-sectional area (CSA) of upper arm muscles on MRI, Narakas classification, EMG results, and elbow muscle function using the Gilbert score. In childhood at follow-up at mean age of 7.7 years, we measured the amount of flexion contractures and the upper arm peak force (Newton). Statistical analysis is used to assess relations between these parameters.

Results

 Flexion contractures of greater than 10 degrees occurred in 55% of our patient group. The relation between the parameters in infancy and the flexion contractures in childhood is almost nonexistent. Only the Narakas classification was related to the development of flexion contractures in childhood (p = 0.006). Infant muscle CSA is related to childhood peak muscle force.

Conclusion

 The role of infancy upper arm muscle hypotrophy/hypertrophy, reinnervation, and early elbow muscle function in the development of childhood elbow contractures remains unclear. In this cohort prediction of childhood flexion, contractures were not possible using infancy neuromuscular parameters. We suggest that contractures might be an adaptive process to optimize residual muscle function.     

Severity and Patterns of Blood-Nerve Barrier Breakdown in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Correlations with Clinical Subtypes

Objective

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is currently classified into clinical subtypes, including typical and atypical forms (multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) and distal acquired demyelinating symmetric neuropathy (DADS)). The aim of this study was to elucidate the patterns and severity of breakdown of the blood-nerve barrier (BNB) in each CIDP subtype.

Methods

We evaluated the effects of sera obtained from patients with typical CIDP, MADSAM and DADS and control subjects on the expression levels of tight junction proteins and transendothelial electrical resistance (TEER) value in human peripheral nerve microvascular endothelial cells (PnMECs).

Results

The sera obtained from the patients with the three clinical phenotypes of CIDP decreased the amount of claudin-5 protein levels and TEER values in the PnMECs. In addition, the sera obtained from typical CIDP patients more prominently reduced claudin-5 protein levels and TEER values in the PnMECs than did that obtained from the MADSAM and DADS patients. Furthermore, the severity of BNB disruption after exposure to the sera was associated with higher Hughes grade, lower MRC score, more pronounced slowing of motor nerve conduction in the median nerve and higher frequency of abnormal temporal dispersion.

Conclusions

Sera derived from typical CIDP patients destroy the BNB more severely than those from MADSAM or DADS patients. The extent of BNB disruption in the setting of CIDP is associated with clinical disability and demyelination in the nerve trunk. These observations may explain the phenotypical differences between CIDP subtypes.     

Habituation to Experimentally Induced Electrical Pain during Voluntary-Breathing Controlled Electrical Stimulation (BreEStim)

Objective

Painful peripheral electrical stimulation to acupuncture points was found to cause sensitization if delivered randomly (EStim), but induced habituation if triggered by voluntary breathing (BreEStim). The objective was to systematically compare the effectiveness of BreEStim and EStim and to investigate the possible mechanisms mediating the habituation effect of BreEStim.

Methods

Eleven pain-free, healthy subjects (6 males, 5 females) participated in the study. Each subject received the BreEStim and EStim treatments in a random order at least three days apart. Both treatments consisted of 120 painful but tolerable stimuli to the ulnar nerve at the elbow on the dominant arm. BreEStim was triggered by voluntary breathing while EStim was delivered randomly. Electrical sensation threshold (EST) and electrical pain threshold (EPT) were measured from the thenar and hypothenar eminences on both hands at pre-intervention and 10-minutes post-intervention.

Results

There was no difference in the pre-intervention baseline measurement of EST and EPT between BreEStim and EStim. BreEStim increased EPT in all tested sites on both hands, while EStim increased EPT in the dominant hypothenar eminence distal to the stimulating site and had no effect on EPT in other sites. There was no difference in the intensity of electrical stimulation between EStim and BreEStim.

Conclusion

Our findings support the important role human voluntary breathing plays in the systemic habituation effect of BreEStim to peripheral painful electrical stimulation.     

Complications of Treating Terrible Triad Injury of the Elbow: A Systematic Review

Objective

Terrible triad injury of the elbow (TTIE), comprising elbow dislocation with radial head and coronoid process fracture, is notoriously challenging to treat and has typically been associated with complications and poor outcomes. The objective of this systematic review was to summarize the most recent available evidence regarding functional outcomes and complications following surgical management of TTIE.

Methods

Medline, EMBASE, Cochrane Library, and Google Scholar were searched to identify relevant studies, which were included if they were retrospective or prospective in design, involved participants who had TTIE, and were published in English. Outcomes of interest were functional outcomes and complications.

Results

Sixteen studies, involving 312 patients, were included in the systematic review. Mean follow up after surgery was typically 25 to 30 months. Mean Mayo elbow performance scores ranged from 78 to 95. Mean Broberg-Morrey scores ranged from 76 to 90. Mean DASH scores ranged from 9 to 31. The proportion of patients who required reoperation due to complications ranged from 0 to 54.5% (overall  = 70/312 [22.4%]). Most of these complications were related to hardware fixation problems, joint stiffness, joint instability, and ulnar neuropathy. The most common complications that did not require reoperation were heterotopic ossification (39/312 [12.5%] patients) and arthrosis (35/312 [11.2%] patients).

Conclusions

The results of this systematic review indicate that functional outcomes after surgery for TTIE are generally satisfactory and that complications are common. Further research is warranted to determine which surgical techniques optimize functional outcomes and reduce the risk of complications.     

Overexpression of mutant HSP27 causes axonal neuropathy in mice

Background

Mutations in heat shock 27 kDa protein 1 (HSP27 or HSPB1) cause distal hereditary motor neuropathy (dHMN) or Charcot-Marie-Tooth disease type 2 F (CMT2F) according to unknown factors. Mutant HSP27 proteins affect axonal transport by reducing acetylated tubulin.

Results

We generated a transgenic mouse model overexpressing HSP27-S135F mutant protein driven by Cytomegalovirus (CMV) immediate early promoter. The mouse phenotype was similar to dHMN patients in that they exhibit motor neuropathy. To determine the phenotypic aberration of transgenic mice, behavior test, magnetic resonance imaging (MRI), electrophysiological study, and pathology were performed. Rotarod test showed that founder mice exhibited lowered motor performance. MRI also revealed marked fatty infiltration in the anterior and posterior compartments at calf level. Electrophysiologically, compound muscle action potential (CMAP) but not motor nerve conduction velocity (MNCV) was reduced in the transgenic mice. Toluidine staining with semi-thin section of sciatic nerve showed the ratio of large myelinated axon fiber was reduced, which might cause reduced locomotion in the transgenic mice. Electron microscopy also revealed abundant aberrant myelination. Immunohistochemically, neuronal dysfunctions included elevated level of phosphorylated neurofilament and reduced level of acetylated tubulin in the sural nerve of transgenic mice. There was no additional phenotype besides motor neuronal defects.

Conclusions

Overexpression of HSP27-S135F protein causes peripheral neuropathy. The mouse model can be applied to future development of therapeutic strategies for dHMN or CMT2F.

Electronic supplementary material

The online version of this article (doi:10.1186/s12929-015-0154-y) contains supplementary material, which is available to authorized users.     

MR Imaging of Patients with Lateral Epicondylitis of the Elbow: Is the Common Extensor Tendon an Isolated Lesion?

Objective

To investigate whether an injury of the common extensor tendon (CET) is associated with other abnormalities in the elbow joint and find the potential relationships between these imaging features by using a high-resolution magnetic resonance imaging (MRI).

Methods

Twenty-three patients were examined with 3.0 T MR. Two reviewers were recruited for MR images evaluation. Image features were recorded in terms of (1) the injury degree of CET; (2) associated injuries in the elbow joint. Spearman’s rank correlation analysis was performed to analyze the relationships between the injury degree of CET and associated abnormalities of the elbow joint, correlations were considered significant at p<0.05.

Results

Total 24 elbows in 23 patients were included. Various degrees of injuries were found in total 24 CETs (10 mild, 7 moderate and 7 severe). Associated abnormalities were detected in accompaniments of the elbow joints including ligaments, tendons, saccussynovialis and muscles. A significantly positive correlation (r = 0.877,p<0.01) was found in injuries of CET and lateral ulnar collateral ligament (LUCL).

Conclusion

Injury of the CET is not an isolated lesion for lateral picondylitis, which is mostly accompanied with other abnormalities, of which the LUCL injury is the most commonly seen in lateral epicondylitis, and there is a positive correlation between the injury degree in CET and LUCL.     

Preliminary evaluation of the sural nerve using 22-MHz ultrasound: a new approach for evaluation of diabetic cutaneous neuropathy

Background

The application of 22-MHz high-frequency ultrasound allows for visualization of the inner part of the sural nerve. The aim of this study was to evaluate the morphological changes of sural nerves in patients with type 2 diabetes mellitus using ultrasound.

Materials and Methods

The thickness/width (T/W) ratio, the cross-sectional area (CSA) of the sural nerves and the maximum thickness (MT) of the nerve fascicles were measured in 100 patients with type 2 diabetes mellitus and 50 healthy volunteers using 22-MHz ultrasound. Receiver operating characteristic (ROC) curves were plotted to determine the optimal cut-off values as well as the sensitivities and specificities. All parameters were significantly different between the subject and control groups. The ROC curves demonstrated that the MT was the most predictive of diabetic cutaneous neuropathy, with an optimal cut-off value of 0.365 mm that yielded a sensitivity of 90.3% and a specificity of 87.7%.

Conclusions

The results of this study suggest that 22-MHz ultrasound may be a valuable tool for evaluating diabetic cutaneous nerve neuropathy.     

Environmental Factors Associated with Disease Progression after the First Demyelinating Event: Results from the Multi-Center SET Study

Objectives

To investigate the associations of environmental MS risk factors with clinical and MRI measures of progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event.

Methods

We analyzed 211 CIS patients (age: 28.9±7.8 years) enrolled in the SET study, a multi-center study of high-risk CIS patients. Pre-treatment samples were analyzed for IgG antibodies against cytomegalovirus (anti-CMV), Epstein Barr virus (EBV) early nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA), early antigen-diffuse (EA-D), 25 hydroxy-vitamin D3 and cotinine levels and HLA DRB1*1501 status. The inclusion criteria required evaluation within 4 months of the initial demyelinating event, 2 or more brain MRI lesions and the presence of two or more oligoclonal bands in cerebrospinal fluid. All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months.

Results

The time to first relapse decreased and the number of relapses increased with anti-CMV IgG positivity. Smoking was associated with increased number and volume of contrast-enhancing lesions (CEL) during the 2-year period. The cumulative number of CEL and T2 lesions during the 2-year period was greater for individuals in the highest quartile of anti-EBV VCA IgG antibodies. The percent loss of brain volume was increased for those in the highest quartile of with anti-EBV VCA IgG antibodies.

Conclusions

Relapses in CIS patients were associated with CMV positivity whereas anti-EBV VCA positivity was associated with progression on MRI measures, including accumulation of CEL and T2 lesions and development of brain atrophy.     

Intravitreal Transplantation of Human Umbilical Cord Blood Stem Cells Protects Rats from Traumatic Optic Neuropathy

Objectives

To treat traumatic optic neuropathy (TON) with transplantation of human umbilical cord blood stem cells (hUCBSC) and explore how transplanted stem cells participate in the neuron repairing process.

Methods

A total of 195 Sprague-Dawley rats were randomly assigned to three groups: sham-surgery, optic nerve injury, and stem cell transplant group. Optic nerve injury was established in rats by directly clamping the optic nerve for 30 seconds. hUCBSC was microinjected into the vitreous cavity of injured rats. Optic nerve function was evaluated by flash visual evoked potentials (F-VEP). Apoptosis in retina tissues was detected by TUNEL staining. GRP78 and CHOP gene expression was measured by RT-PCR.

Results

After injury, transplantation of hUCBSC significantly blunted a reduction in optic nerve function indicated by smaller decreases in amplitude and smaller increases in peak latency of F-VEP waveform compared to the injury alone group. Also, significant more in retinal ganglion cell (RGC) count and less in RGC apoptosis were detected after transplantation compared to injured rats. The protective effect correlated with upregulated GRP78 and downregulated CHOP mRNA expression.

Conclusion

Intravitreal transplantation of hUCBSCs significantly blunted a reduction in optic nerve function through increasing RGC survival and decreasing retinal cell apoptosis. The protective role of transplantation was associated with upregulation of GRP78 expression and downregulation of CHOP expression in retinal cells.     

Scapular Winging Secondary to Apparent Long Thoracic Nerve Palsy in a Young Female Swimmer

Background

 In neurological diseases, winging of the scapula occurs because of serratus anterior muscle dysfunction due to long thoracic nerve palsy, or trapezius muscle dysfunction due to accessory nerve palsy. Several sports can cause long thoracic nerve palsy, including archery and tennis. To our knowledge, this is the first report of long thoracic nerve palsy in an aquatic sport.

Objective

 The present study is a rare case of winging of the scapula that occurred during synchronized swimming practice.

Methods

 The patient''s history with the present illness, examination findings, rehabilitation progress, and related medical literature are presented.

Results

 A 14-year-old female synchronized swimmer had chief complaints of muscle weakness, pain, and paresthesia in the right scapula. Upon examination, marked winging of the scapula appeared during anterior arm elevation, as did floating of the superior angle. After 1 year of therapy, right shoulder girdle pain and paresthesia had disappeared; however, winging of the scapula remained.

Conclusions

 Based on this observation and the severe pain in the vicinity of the second dorsal rib, we believe the cause was damage to the nerve proximal to the branch arising from the upper nerve trunk that innervates the serratus anterior.     

Comparison of Optic Disc Morphology of Optic Nerve Atrophy between Compressive Optic Neuropathy and Glaucomatous Optic Neuropathy

Objectives

To compare the optic nerve head (ONH) structure between compressive optic neuropathy (CON) and glaucomatous optic neuropathy (GON), and to determine whether selected ONH quantitative parameters effectively discriminate between GON and CON, especially CON cases presenting with a glaucoma-like disc.

Methods

We prospectively assessed 34 patients with CON, 34 age-matched patients with moderate or severe GON, and 34 age-matched healthy control subjects. The quantitative parameters of ONH structure were compared using the Heidelberg Retina Tomograph 2 (HRT2) and Spectralis optical coherence tomography with an enhanced depth imaging method.

Results

The mean and maximum cup depths of CON were significantly smaller than those with GON (P<0.001 and P<0.001, respectively). The distance between Bruch''s membrane opening and anterior surface of the lamina cribrosa (BMO-anterior LC) of CON was also significantly smaller than that of glaucoma but was similar to that of the healthy group (P<0.001 and P = 0.47, respectively). Based on Moorfields regression analysis of the glaucoma classification of HRT2, 15 eyes with CON were classified with a glaucoma-like disc. The cup/disc area ratio did not differ between cases of CON with a glaucoma-like disc and cases of GON (P = 0.16), but the BMO-anterior LC and mean and maximum cup depths of CON cases with a glaucoma-like disc were smaller than those in GON (P = 0.005, P = 0.003, and P = 0.001, respectively).

Conclusions

Measurements of the cup depths and the LC depth had good ability to differentiate between CON with a glaucoma-like disc and glaucoma. There was no laminar remodeling detected by laminar surface position in the patients with CON compared to those with GON.     

A Novel and Selective Poly (ADP-Ribose) Polymerase Inhibitor Ameliorates Chemotherapy-Induced Painful Neuropathy

Background

Chemotherapy-induced neuropathy is the principle dose limiting factor requiring discontinuation of many chemotherapeutic agents, including cisplatin and oxaliplatin. About 30 to 40% of patients receiving chemotherapy develop pain and sensory changes. Given that poly (ADP-ribose) polymerase (PARP) inhibition has been shown to provide neuroprotection, the current study was developed to test whether the novel PARP inhibitor compound 4a (analog of ABT-888) would attenuate pain in cisplatin and oxaliplatin-induced neuropathy in mice.

Results

An established chemotherapy-induced painful neuropathy model of two weekly cycles of 10 intraperitoneal (i.p.) injections separated by 5 days rest was used to examine the therapeutic potential of the PARP inhibitor compound 4a. Behavioral testing using von Frey, paw radiant heat, cold plate, and exploratory behaviors were taken at baseline, and followed by testing at 3, 6, and 8 weeks from the beginning of drug treatment.

Conclusion

Cisplatin-treated mice developed heat hyperalgesia and mechanical allodynia while oxaliplatin-treated mice exhibited cold hyperalgesia and mechanical allodynia. Co-administration of 50 mg/kg or 25 mg/kg compound 4a with platinum regimen, attenuated cisplatin-induced heat hyperalgesia and mechanical allodynia in a dose dependent manner. Similarly, co-administration of 50 mg/kg compound 4a attenuated oxaliplatin-induced cold hyperalgesia and mechanical allodynia. These data indicate that administration of a novel PARP inhibitor may have important applications as a therapeutic agent for human chemotherapy-induced painful neuropathy.     

Multi-Parametric Spinal Cord MRI as Potential Progression Marker in Amyotrophic Lateral Sclerosis

Objective

To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients.

Materials and Methods

After a first MRI (MRI₁), 29 ALS patients were clinically followed during 12 months; 14/29 patients underwent a second MRI (MRI₂) at 11±3 months. Cross-sectional area (CSA) that has been shown to be a marker of lower motor neuron degeneration was measured in cervical and upper thoracic spinal cord from T2-weighted images. Fractional anisotropy (FA), axial/radial/mean diffusivities (λ_⊥, λ_//, MD) and magnetization transfer ratio (MTR) were measured within the lateral corticospinal tract in the cervical region. Imaging metrics were compared with clinical scales: Revised ALS Functional Rating Scale (ALSFRS-R) and manual muscle testing (MMT) score.

Results

At MRI₁, CSA correlated significantly (P<0.05) with MMT and arm ALSFRS-R scores. FA correlated significantly with leg ALFSRS-R scores. One year after MRI₁, CSA predicted (P<0.01) arm ALSFSR-R subscore and FA predicted (P<0.01) leg ALSFRS-R subscore. From MRI₁ to MRI₂, significant changes (P<0.01) were detected for CSA and MTR. CSA rate of change (i.e. atrophy) highly correlated (P<0.01) with arm ALSFRS-R and arm MMT subscores rate of change.

Conclusion

Atrophy and DTI metrics predicted ALS disease progression. Cord atrophy was a better biomarker of disease progression than diffusion and MTR. Our study suggests that multimodal MRI could provide surrogate markers of ALS that may help monitoring the effect of disease-modifying drugs.     

Severe obstetric brachial plexus palsies can be identified at one month of age

Objective

To establish whether severe obstetric brachial plexus palsy (OBPP) can be identified reliably at or before three months of age.

Methods

Severe OBPP was defined as neurotmesis or avulsion of spinal nerves C5 and C6 irrespective of additional C7-T1 lesions, assessed during surgery and confirmed by histopathological examination. We first prospectively studied a derivation group of 48 infants with OBPP with a minimal follow-up of two years. Ten dichotomous items concerning active clinical joint movement and needle electromyography of the deltoid, biceps and triceps muscles were gathered at one week, one month and three months of age. Predictors for a severe lesion were identified using a two-step forward logistic regression analysis. The results were validated in two independent cohorts of OBPP infants of 60 and 13 infants.

Results

Prediction of severe OBPP at one month of age was better than at one week and at three months. The presence of elbow extension, elbow flexion and of motor unit potentials in the biceps muscle correctly predicted whether lesions were mild or severe in 93.6% of infants in the derivation group (sensitivity 1.0, specificity 0.88), in 88.3% in the first validation group (sensitivity 0.97, specificity 0.76) and in 84.6% in the second group (sensitivity of 1.0, specificity 0.66).

Interpretation

Infants with OBPP with severe lesions can be identified at one month of age by testing elbow extension, elbow flexion and recording motor unit potentials (MUPs) in the biceps muscle. The decision rule implies that children without active elbow extension at one month should be referred to a specialized center, while children with active elbow extension as well as active flexion should not. When there is active elbow extension, but no active elbow flexion an EMG is needed; absence of MUPs in the biceps muscle is an indication for referral.     

Motor Function of the Upper-Extremity after Transection of the Second Thoracic Nerve Root during Total En Bloc Spondylectomy

Background

In total en bloc spondylectomy (TES) of upper thoracic spine including the second thoracic (T2) vertebra, T2 nerve roots are usually transected. In this study, we examined the association between transection of the T2 nerve roots and upper-extremity motor function in patients with upper thoracic TES.

Methods

We assessed 16 patients who underwent upper thoracic TES with bilateral transection of the T2 nerve roots. Patients were divided into three groups: 3 patients without any processing of T1 and upper nerve roots (T2 group), 7 with extensive dissection of T1 nerve roots (T1–2 group), and 6 with extensive dissection of T1 and upper nerve roots (C–T2 group). Postoperative upper-extremity motor function was compared between the groups.

Results

Postoperative deterioration of upper-extremity motor function was observed in 9 of the 16 patients (56.3%). Three of the 7 patients in the T1–2 group and all 6 patients in the C–T2 group showed deterioration of upper-extremity motor function, but there was no deterioration in the T2 group. In the T1–2 group, 3 patients showed mild deterioration that did not affect their activities of daily living and they achieved complete recovery at the latest follow-up examination. In contrast, severe dysfunction occurred frequently in the C–T2 group, without recovery at the latest follow-up.

Conclusions

The transection of the T2 nerve roots alone did not result in upper-extremity motor dysfunction; rather, the dysfunction is caused by the extensive dissection of the T1 and upper nerve roots. Therefore, transection of the T2 nerve roots in upper thoracic TES seems to be an acceptable procedure with satisfactory outcomes.     

7 Tesla Magnetic Resonance Imaging to Detect Cortical Pathology in Multiple Sclerosis

Background

Neocortical lesions (NLs) are an important pathological component of multiple sclerosis (MS), but their visualization by magnetic resonance imaging (MRI) remains challenging.

Objectives

We aimed at assessing the sensitivity of multi echo gradient echo (ME-GRE) T₂ ^*-weighted MRI at 7.0 Tesla in depicting NLs compared to myelin and iron staining.

Methods

Samples from two MS patients were imaged post mortem using a whole body 7T MRI scanner with a 24-channel receive-only array. Isotropic 200 micron resolution images with varying T₂ ^* weighting were reconstructed from the ME-GRE data and converted into R₂ ^* maps. Immunohistochemical staining for myelin (proteolipid protein, PLP) and diaminobenzidine-enhanced Turnbull blue staining for iron were performed.

Results

Prospective and retrospective sensitivities of MRI for the detection of NLs were 48% and 67% respectively. We observed MRI maps detecting only a small portion of 20 subpial NLs extending over large cortical areas on PLP stainings. No MRI signal changes suggestive of iron accumulation in NLs were observed. Conversely, R₂ ^* maps indicated iron loss in NLs, which was confirmed by histological quantification.

Conclusions

High-resolution post mortem imaging using R₂ ^* and magnitude maps permits detection of focal NLs. However, disclosing extensive subpial demyelination with MRI remains challenging.     

Facilitating tumor functional assessment by spatially relating 3D tumor histology and in vivo MRI: image registration approach

Background

Magnetic resonance imaging (MRI), together with histology, is widely used to diagnose and to monitor treatment in oncology. Spatial correspondence between these modalities provides information about the ability of MRI to characterize cancerous tissue. However, registration is complicated by deformations during pathological processing, and differences in scale and information content.

Methodology/Principal Findings

This study proposes a methodology for establishing an accurate 3D relation between histological sections and high resolution in vivo MRI tumor data. The key features of the methodology are: 1) standardized acquisition and processing, 2) use of an intermediate ex vivo MRI, 3) use of a reference cutting plane, 4) dense histological sampling, 5) elastic registration, and 6) use of complete 3D data sets. Five rat pancreatic tumors imaged by T2*-w MRI were used to evaluate the proposed methodology. The registration accuracy was assessed by root mean squared (RMS) distances between manually annotated landmark points in both modalities. After elastic registration the average RMS distance decreased from 1.4 to 0.7 mm. The intermediate ex vivo MRI and the reference cutting plane shared by all three 3D images (in vivo MRI, ex vivo MRI, and 3D histology data) were found to be crucial for the accurate co-registration between the 3D histological data set and in vivo MRI. The MR intensity in necrotic regions, as manually annotated in 3D histology, was significantly different from other histologically confirmed regions (i.e., viable and hemorrhagic). However, the viable and the hemorrhagic regions showed a large overlap in T2^*-w MRI signal intensity.

Conclusions

The established 3D correspondence between tumor histology and in vivo MRI enables extraction of MRI characteristics for histologically confirmed regions. The proposed methodology allows the creation of a tumor database of spatially registered multi-spectral MR images and multi-stained 3D histology.