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A summary of some of the recently published, seminal papers on nerve pathology
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.250723
Pourmemari MH, et al. Carpal tunnel release: Lifetime prevalence, annual incidence, and risk factors. Muscle Nerve 2018;58:497-502. This longitudinally designed study from Finland looked at 7,977 individuals (aged 30 years or more) to identify the risk factors, evaluate the lifetime prevalence and the annual incidence of carpal tunnel release (CTR). The determinants evaluated included personal and occupational factors, co-morbid illnesses as well as physical examinations, and laboratory tests factors. It was found that the lifetime prevalence of CTR was 3.1%, with an incidence rate of 1.73 per 1,000 person years. It was also evident that the higher incidence of CTR was associated with female gender (hazard ratio [HR] 1.8), age between 40–49 years (HR52.5), a higher educational status (HR = 0.6), a higher body mass index (HR = 1.7) and concomitant hand osteoarthritis (HR = 2.4, CI 1.4–3.9) without any association with other known factors like smoking, leisure time physical activity, waist circumference, diabetes, rheumatoid arthritis, hypothyroidism, and workload. The authors concluded that CTR was a fairly common procedure (more than 3% of people undergo surgery for CTS in their lifetime) and presence of obesity and hand osteoarthritis significantly increased the incidence of CTR. Contributed by Dr Raghavendra K. Kamel JT. Single-fiber F waves compared with conventional surface F waves, and their utility in detecting early diabetic neuropathy. Muscle Nerve 2018;58:665-70. In this single centre study, the authors tried to address the utilisation of single-fiber F-wave (SFF-wave) technique in the detection of early diabetes-related neuropathy (DPN) in comparison to the conventional surface F wave studies (CF waves). The electrophysiological findings of sixteen subjects with type 1 diabetes mellitus (T1DM) were compared with 16 age- and height-matched controls. Among the diabetic subjects, 5 and 11 had a mild and no neuropathy, respectively, as per the Michigan Diabetic Neuropathy Score (MDNS). The diabetic subjects had a mean duration of illness of 22 years and a mean glycated hemoglobin of 7.8 ± 1.0 [standard deviation (SD)]. The overall sensitivity in differentiating neuropathy versus no neuropathy was 75% (12 of 16 patients) for SFF waves, and 44% (7 of 16 patients) for the CF waves. The subjects with mild neuropathy were picked up by both the CF and SFF studies. The CF waves studies were able to demonstrate subclinical abnormalities in only 18% subjects, but with the use of the SFF-wave, the detection rate increased to 64%. On further exploring the F-wave parameters, the minimum and maximum F-wave latency (FMIN and FMAX) was able to detect neuropathy but F wave dispersion (FDISP) provided additional information with the SFF method. F-wave persistence (Fp) lacked sensitivity in both the groups. The authors suggested that a higher yield with SFF studies was probably due to its ability to detect segmental involvement that occurs in early DPN, which many not be picked up by the standard CN test which only assesses the entire length of the motor nerves. In conclusion, the use of the SFF-wave technique detects more abnormalities than the technique that utilizes the CF waves in early stages of diabetic neuropathy, even before clinical manifestations appear. Contributed by Dr Raghavendra K. Alrajeh M, et al. Neuromuscular ultrasound in electrically non-localizable ulnar neuropathy. Muscle Nerve 2018;58:655-9. In this single centre prospective study, the authors aimed to evaluate the utilisation of high-resolution ultrasound (HRUS) among patients with ulnar neuropathy in whom the electrophysiological studies had shown axonal but non-localizing pattern of ulnar nerve involvement. Fifty-six subjects with ulnar neuropathy were enrolled. 21% of these patients demonstrated the ulnar neuropathy pattern on electrodiagnostic test (EDx). An abnormal fascicular pattern was demonstrated in all the included subjects. The abnormalities included hypoechoic and enlarged (cross-sectional area >10 mm2) ulnar nerve. It also demonstrated additional findings of structural lesions in two subjects in the form of a large cystic structure in one, and a large neuroma in another subject. Moreover, it was possible to map the exact area of lesion on the ulnar nerve in 9 subjects. With these findings, the authors concluded that HRUS was able to localize ulnar neuropathy in subjects in whom the electrophysiology was abnormal but non-localizing. Contributed by Dr Raghavendra K. Kandula T, et al. Chemotherapy-induced peripheral neuropathy in long-term survivors of childhood cancer: Clinical, neurophysiological, functional, and patient-reported outcomes. JAMA Neurol 2018;75:980-8. This study was a cross-sectional observational study done at a single tertiary hospital between April 2015 and December 2016. The authors provided a multimodal assessment of chemotherapy-induced peripheral neuropathy among long-term survivors of childhood cancer for this study. The enrolled cancer survivors had undergone chemotherapy for extracranial malignancy before the age of 17 years. A total of 121 childhood cancer survivors, of which 107 (88.4%) received neurotoxic chemotherapeutic agents, were included in the study; and, of these, 46.7% had further radiotherapy exposure. These 107 subjects were compared to healthy age-matched controls using scales for clinical and functional measures, along with nerve conduction studies for neurophysiological measures. The assessment for neurotoxicity was undertaken at a median age of 16 years, and following a median age of 8.5 years after treatment completion. Vinca alkaloids (71.1%) and platinum compounds (16.5%) were the main neurotoxic agents used. Clinically, peripheral neuropathy was found in 50.5% of the patients exposed to neurotoxic chemotherapy as compared to only 14% among controls. The higher tumor neuropathy scores (TNS) were more prevalent in the cisplatin-containing protocol (83%), followed by the vinca alkaloid- (29%) containing protocol. Electrophysiology wise, the neurotoxic chemotherapy treated group were associated with lower limb predominant sensory axonal neuropathy (mean amplitude reduction, 5.8 μV; 95% confidence interval [CI], 2.8-8.8; P <.001). From a functional perspective, reduced manual dexterity and distal sensations were noted among children and adults. The higher score on clinical assessment was associated with worst scores in patient-reported global quality of life and physical functioning measures. The study also found long term neurotoxicity with cisplatinum compared to vinca alkaloids. The authors concluded that long-term deficits in clinical, electrophysiological, and functional measures of peripheral neuropathy were common among the childhood cancer survivors with concurrent deficits in patient-reported outcome (PRO) measures. Contributed by Dr Raghavendra K. Dirlikov E, et al. Clinical features of Guillain-Barré syndrome with vs without zika virus infection, Puerto Rico, 2016. JAMA Neurol 2018;75:1089-97. This interesting study was undertaken at Puerto Rico during the Zika virus (ZIKV) epidemic during which an increased incidence of Guillain-Barré syndrome (GBS) was noted and reported. The authors evaluated the specific clinical features of GBS associated with ZIKV infection. The public health surveillance data during the ZIKV epidemic was reviewed and a total of 123 confirmed GBS cases diagnosed using the Brighton Collaboration criteria were identified. 107 out of 123 subjects were tested for evidence of ZIKV infection by real-time reverse transcriptase–polymerase chain reaction; serum and cerebrospinal fluid were also tested by IgM enzyme-linked immunosorbent assay. Among the 107 GBS subjects, 66.36% patients tested positive for ZIKV infection. Majority of these subjects were followed up with telephonic interviews, 6 months after the onset of the neurological illness. The patients were evaluated for acute and long-term clinical characteristics of GBS associated with ZIKV infection. The median age was 54 years with a higher representation by males (55.3%). Among the acute manifestations, GBS associated with ZIKV infection, and a higher incidence of cranial neuropathy features in the form of facial weakness, dysphagia, shortness of breath, and facial paraesthesia were noted. They also had a higher admission to the intensive care unit along with the need for mechanical ventilation. On laboratory finding assessment, the levels of proteins in the cerebrospinal fluid were found to be significantly higher in GBS with ZIKV infection. At a six-month follow up period, the GBS associated with ZIKV infection group had a higher sequel of tearing abnormalities, pain as well as motor deficit, the latter measured as difficulty in drinking from a cup. Contributed by Dr Raghavendra K. Sneag DB, et al. Brachial plexitis or neuritis? MRI features of lesion distribution in Parsonage–Turner syndrome. Muscle Nerve 2018;58:359–66. The authors attempted to characterize the lesion distribution in Parsonage–Turner syndrome (PTS) using high-resolution magnetic resonance imaging (MRI). To accomplish this, MRIs of 27 patients with clinically confirmed PTS were reviewed. Two radiologists independently evaluated the brachial plexus proper, side and terminal plexus branches, and more distal, upper extremity nerves. All patients had at least one clinically involved nerve. The MRI revealed that the plexus appeared normal in 24 of 27 patients; in 3 other patients, signal hyperintensity was seen immediately proximal to the take-off of abnormal side or terminal branch nerves. Focal intrinsic constrictions were detected in 32 of 38 nerves. MRI interobserver agreement was high (Cohen's κ = 0.839). MRI findings, corroborated by electro-diagnostic testing, detected the localized abnormalities present in the plexus branches and peripheral nerves, suggesting that PTS is characterized by one or more mononeuropathies, rather than changes involving a portion of or the complete plexus proper. These results may improve the diagnosis, prognostication, and management of this disorder. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Nandedkar SD, et al. Motor unit number index: Guidelines for recording signals and their analysis. Muscle Nerve 2018;58:374–80. This study proposes guidelines for motor unit number index (MUNIX) recording and analysis. MUNIX was measured in control participants and in patients with amyotrophic lateral sclerosis. Changes in MUNIX values due to E1 electrode position, number of surface electromyography interference pattern (SIP) epochs, SIP epoch duration, force of contraction, and outlier data points were investigated. MUNIX depends on optimized compound muscle action potential (CMAP) amplitude. Individual muscles showed variations when the number of epochs was low or when the SIP duration was short. A longer SIP duration allowed for a better recognition of artifacts. The results of MUNIX were affected by SIP values at all force levels but was more affected when the SIP area was low. The authors recommend changing the E1 electrode position to maximize the CMAP amplitude. Twenty or more SIP signals of 500-ms duration should be recorded by using force levels ranging from slight to maximum. Traces should be reviewed to identify and exclude signals with tremor or solitary spikes. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Gilmore KJ, et al. Reductions in muscle quality and quantity in chronic inflammatory demyelinating polyneuropathy patients assessed by magnetic resonance imaging. Muscle Nerve 2018;58:396–401. The authors attempted to determine the cause of weakness in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) which they thought to be related to muscle weakness. To study this, 12 patients with CIDP (mean age 61 years) and 10 age-matched (mean age 59 years) controls were assessed for ankle dorsiflexion strength, and two different MRI scans (T1 and T2) of leg musculature. The isometric strength was found to be 36% lower in CIDP patients compared with controls. The tibialis anterior muscle volumes of CIDP patients were smaller by ~17% compared with controls, and the non-contractile tissue volume was ~58% greater in CIDP patients. When normalized to total muscle or corrected contractile volume, the strength was ~29% and ~18% lower, respectively, in CIDP patients. These results provide an insight into the structural integrity of muscle contractile proteins and the pathologic changes to the whole-muscle tissue composition that contribute to impaired muscle functions in CIDP. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Wang JC, et al. Sonographic median nerve change after steroid injection for carpal tunnel syndrome. Muscle Nerve 2018;58:402–6. The authors attempted to investigate the use of sonographic changes of the median nerve after steroid injection for carpal tunnel syndrome (CTS). Sixty-two patients with CTS were included. The Boston Carpal Tunnel Questionnaire was administered, and ultrasonographic examinations were performed before and at 2, 6, and 12 weeks after steroid injection. At 12 weeks, general improvement was scored on a 6-point Likert scale. After treatment, the cross-sectional area (CSA) of the median nerve was significantly reduced at 2-, 6-, and 12-week follow-up intervals (for each, P < 0.001, analysis of variance). The “significant improvement” group (n = 39) had a significantly greater reduction in the CSA at the carpal tunnel inlet (P = 0.014) and CSA in the proximal carpal tunnel (P = 0.003) compared with the “little/no improvement” group (n = 23). The authors concluded that sonographic measurement of CSA may be considered complementary to the standard clinical evaluation in monitoring of treatment response in patients with CTS. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Kim SW, et al. Risk factors for osteoporosis in chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 2018;58:407–12. The authors evaluated bone mineral density (BMD) in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), who possess multiple risk factors for osteoporosis. The authors retrospectively compared the BMD of CIDP patients with that of normal controls, and evaluated the clinical factors associated with osteoporosis. The total BMD was lower in CIDP patients than in normal controls (P = 0.017). In a comparison of 16 osteoporotic CIDP patients with 25 non-osteoporotic patients, the cumulative prednisolone dose was lower (P = 0.022) and the duration from disease onset to BMD measurement was shorter (P = 0.014) in osteoporotic patients than in non-osteoporotic patients. Function, as measured by modified Rankin scale score within 3 years of the BMD measurement, was worse in osteoporotic than in non-osteoporotic patients (P = 0.008). BMD in CIDP patients was significantly lower than in normal controls. The authors concluded that the functional status rather than cumulative steroid dose was associated with osteoporosis. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Zhao Y, et al. Histone deacetylase inhibition inhibits brachial plexus avulsion-induced neuropathic pain. Muscle Nerve 2018;58:434–40. Neuropathic pain induced by brachial plexus avulsion (BPA) is a pathological condition. The authors hypothesized that inhibition of histone deacetylase (HDAC) could suppress BPA-induced neuropathic pain through inhibition of transient reception potential (TRP) overexpression and protein kinase B (Akt)-mediated mammalian target of rapamycin (mTOR) activation. The authors generated a rat BPA model; administered HDAC inhibitor, tricostatin A (TSA), for 7 days post-surgery; and, assessed the effects on HDAC expression, Akt phosphorylation, neuroinflammation, and mTOR activation. The TSA treatment alleviated BPA-induced mechanical hyperalgesia, suppressed Akt phosphorylation, and increased HDAC. They found suppressed proinflammatory cytokine levels, TRP subfamily V member 1 and TRP subfamily M member 8 expression, and mTOR activity in TSA-treated BPA rats. The authors suggested that altered HDAC and Akt signaling are involved in BPA-induced neuropathic pain, and that inhibition of HDAC could be an effective therapeutic approach in reducing neuropathic pain. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Davis JL, et al. Somatotopic heat pain thresholds and intraepidermal nerve fibers in health. Muscle Nerve 2018;58:509–16. The authors hypothesize that, for sequential and somatotopic assessment of small fiber neuropathy, heat pain (HP) tests of hypoalgesia might be used instead of decreased counts of epidermal nerve fibers (ENFs), but then healthy subject reference values of HP thresholds are needed. Using the Computer Assisted Sensation Evaluator IVc system, HP thresholds of hypoalgesia were estimated for 10 unilateral sites and counts of ENFs for 4 of them in healthy subjects. In healthy subjects, small but statistically significant differences of both HP thresholds of hypoalgesia and counts of ENFs were observed among the tested sites. Significant correlations between HP thresholds and counts of ENFs were not found. For the studied somatotopic sites, the authors provided ≥95th and ≥99th percentile reference limits for HP 0.5 and 5 of 1–10 HP thresholds of hypoalgesia and decreased counts of ENFs at ≤5th and ≤1st percentile levels. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Michael AE, et al. Is triceps hypertrophy associated with ulnar nerve luxation? Muscle Nerve 2018;58:523–7. The authors explored whether hypertrophy of the triceps brachii muscle was more frequently accompanied by nerve luxation. To investigate, the authors used a cross-sectional design to study a group of amateur bodybuilders (n = 31) in a comparison with a group of age-matched healthy controls (n = 31). Triceps hypertrophy was determined clinically and sonographically. The position of the ulnar nerve in relation to the medial epicondyle was classified according to a graded (0–4) scale. In full flexion of 62 hypertrophic arms, 22 (35.5%) subjects revealed subluxation and 27 (43.5%) complete luxation. In the controls, 21 (33.9%) subjects demonstrated subluxation and 10 (16.1%) complete luxation. The authors concluded that a higher frequency of ulnar nerve luxation in the arms with a hypertrophic triceps indicates that triceps muscle mass may be a factor that is contributing to ulnar nerve luxation. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Tremp M, et al. Regeneration of nerve crush injury using adipose-derived stem cells: A multimodal comparison. Muscle Nerve 2018;58:566–72. The authors evaluated the effect of inection of rat adipose-derived stem cells (rASC) in 2 different settings of sciatic crush injury model to restore full function following nerve crush injuries. In the first group, after 14 days of nerve crush injury, rASCs were injected distal to the lesion under ultrasound guidance. In the other group, alleviation of compression through clip removal (CR) was combined with epineural injection of rASCs. Gait analyses, MRI, gastrocnemius muscle weight ratio (MWR), and histomorphometry were performed for outcome analysis. CR combined with rASC injection resulted in less muscle atrophy, as evidenced by MWR. These findings are further supported by better functional and anatomical outcomes. Animals treated with CR and epineural stem cell injection showed an enhanced anatomical and functional recovery. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Silvia Parra JV, et al. Neurophysiological study of the radial nerve variant in the innervation of the dorsomedial surface of the hand. Muscle Nerve 2018;58:732–5. Sensory innervation of the dorsomedial surface of the hand usually depends on the dorsal ulnar nerve (DUN). Innervation in this area by the superficial radial nerve (SRN) has been described as a normal variant. The authors studied 358 patients using nerve conduction of the DUN and SRN with dorsomedial recording. Each hand was classified into the usual innervation (only DUN response), mixed variant (response of both nerves), or complete variant (only SRN response). Mixed innervation was found in 14.2% of hands and complete innervation was found in 6.8% of hands, mostly unilaterally. No statistically significant differences were observed in age, sex, or clinical suspicion between the usual and the variant innervation. The potential amplitude after SRN stimulation was greater in the complete variant. The authors concluded that it is important to know the characteristics of this variant in order to avoid diagnostic errors and to prevent iatrogenic lesions during surgery performed on the dorsum of the wrist. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Li X, et al. Motor unit number estimation of human abductor hallucis from a compound muscle action potential scan. Muscle Nerve 2018;58:735–7. The authors of this study performed motor unit number estimation (MUNE) of the abductor hallucis (AH) muscle from 16 healthy control participants on the basis of compound muscle action potential (CMAP) scan. Muscle responses to electrical stimuli ranging from subthreshold to supramaximal intensity were recorded, and MUNE was determined from a model of the responses (MScanFit program). The average values of CMAP amplitude and MUNE of the AH for the right and left sides (combined) were 19.6 ± 0.75 mV and 127 ± 5mV (mean ± standard error), respectively. The findings of this study provide useful information about the motor unit numbers of the AH. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Šinkūnaitė L, et al. Focal neurogenic muscle hypertrophy and fasciculations in multifocal motor neuropathy. Muscle Nerve 2018 https://doi.org/10.1002/mus. 26185 Multifocal motor neuropathy (MMN) is a rare, chronic, immune-mediated neuropathy characterized by slowly progressive asymmetric weakness of the limbs and muscular atrophy. Motor conduction block (CB) at sites other than those attributable to entrapment is the electrophysiologic hallmark that distinguishes MMN from motor neuron disease; however, it may not be found in some patients, especially with activity-dependent CB or CB located in segments not routinely assessed by electrophysiologic examinations. In such cases, plexus T2 short-tau inversion recovery (T2-STIR) MRI or ultrasonography may help to diagnose MMN. In this report, the authors describe the case of a woman who developed left radial palsy at 38 years of age. A few months later, her examination revealed a Medical Research Council (MRC) motor score of 3/5 in extensors of the wrist (and fingers) and 4/5 in both triceps brachii and interosseous muscles of the hand. The initial electrophysiologic study showed focal CB in the left radial and median nerves, decreased compound muscle action potential (CMAP) amplitude in the left radial nerve, and no sensory involvement in the upper limbs. Needle electromyography showed large-amplitude motor unit potentials with reduced recruitment in the left first dorsal interosseous, abductor pollicis brevis, brachioradialis, and extensor digitorum communis muscles, with fibrillation potentials in the left extensor digitorum communis muscle. Anti-ganglioside antibody and anti-voltage-gated potassium channel (anti-VGKC) antibody titers were normal. After a diagnosis of MMN, she was successfully treated with intravenous immunoglobulin (IVIg: 2 g/kg every 4–5 months) for 17 years, during which she remained stable, with only slight weakness of extension at the left elbow (MRC: 4/5). Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Prasad SC, et al. Surgical management of intrinsic tumors of the facial nerve. Neurosurgery 2018;83:740–52 This study reviewed the outcomes of surgical management of facial nerve tumors and cable nerve graft interpositioning. A retrospective analysis was performed at a referral center for skull base pathology. One hundred and fifteen patients who were surgically treated for facial nerve tumors were included. In case of nerve interruption during surgery, the cable nerve interpositioning technique was employed wherein the facial nerve palsy lasted for less than 1-year duration. In cases of facial nerve palsy lasting for greater than 1 year, the nerve was restituted by a hypoglossal facial coaptation. Various degrees of progressive paralysis were seen in 84 (73%) cases. Sixty nine (60%) of the tumors involved multiple segments of the facial nerve. Sixty-two (53.9%) tumors involved the geniculate ganglion. Seventy four (64.3%) of the cases were schwannomas. Hearing preservation surgeries were performed in 60 (52.1%) patients. Ninety one (79.1%) of the nerves that were sectioned in association with tumor removal were restituted primarily by interposition cable grafting. The mean preoperative House-Brackmann grading of the facial nerve was 3.6. The mean immediate postoperative grading was 5.4, which recovered to a mean of 3.4 at the end of 1 year. In patients with good facial nerve function (House-Brackmann grade I-II), a wait-and-scan approach is recommended. In the cases where the facial nerve has been interrupted during surgery, the cable nerve interpositioning technique is a convenient and well-accepted procedure for immediate restitution of the nerve. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Zheng MX, et al. Cortical reorganization in dual innervation by single peripheral nerve. Neurosurgery 2018;83:819–26. This study investigated the cortical reorganization when the phrenic nerve simultaneously innervates the diaphragm and biceps. Rats with complete brachial plexus (C5-T1) injury were subjected to a phrenic nerve–musculocutaneous nerve transfer with end-to-side (n = 15) or end-to-end (n = 15) neurorrhaphy. Rats undergoing brachial plexus avulsion (n = 5) and sham surgery (n = 5) were included as the control group. Behavioral observation, electromyography, and histologic studies were used for confirming peripheral nerve reinnervation. Cortical representations of the diaphragm and reinnervated biceps were studied by intracortical microstimulation techniques before and at months 0.5, 3, 5, 7, and 10 after surgery. At month 0.5 after complete brachial plexus injury, the motor representation of the injured forelimb disappeared. The diaphragm representation was preserved in the “end-to-side” group but was absent in the “end-to-end” group. Rhythmic contraction of biceps appeared in the “end-to-end” and “end-to-side” groups, and the biceps representation reappeared in the original biceps and diaphragmatic areas at months 3 and 5. At month 10, it was completely located in the original biceps area in the “end-to-end” group. Part of the biceps representation remained in the original diaphragm area in the “end-to-side” group. Destroying the contralateral motor cortex did not eliminate respiration-related contraction of biceps. The brain tends to resume biceps representation from the original diaphragm area to the original biceps area following phrenic nerve transfer. The original diaphragm area partly preserves the reinnervated biceps representation after end-to-side transfer. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Wilson TJ, et al. Imaging characteristics predict operative difficulty mobilizing the sciatic nerve for proximal hamstring repair. Neurosurgery 2018;83:931–9. The authors attempted to identify the clinical and/or radiological factors predictive of a difficult intraoperative dissection of the sciatic nerve during proximal hamstring repair. They retrospectively reviewed the medical records and preoperative magnetic resonance imaging of consecutive patients undergoing proximal hamstring repair. They also compared the groups with and without a difficult sciatic nerve dissection. The total cohort consisted of 67 patients. Factors found to increase the likelihood of a difficult sciatic nerve dissection included complete conjoint tendon avulsion, higher maximal amount of tendon retraction, higher degree of imaging abnormality in the sciatic nerve, and higher degree of circumferential relationship of the hematoma to the sciatic nerve. At a threshold of 23 for the Sciatic Nerve Dissection Score, the positive and negative predictive values were 53% and 88%, respectively. For the decision tree, the positive and negative predictive values were 75% and 87%, respectively. The imaging factors associated with a scarred, adherent sciatic nerve that can predict a difficult dissection during proximal hamstring repair were, therefore identified. Two novel methods—the Sciatic Nerve Dissection Score and a decision tree—that can be applied to predict the probability of a difficult sciatic nerve dissection at the time of surgical repair, were presented. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Romanelli P, et al., Image-guided robotic radiosurgery for trigeminal neuralgia. Neurosurgery 2018;83:1023-30. The authors reported the results of the largest single-centre experience on image-guided robotic radiosurgery for TN. A cohort of 138 patients treated with CyberKnife® (Accuray Incorporated, Sunnyvale, California) radiosurgery with a minimum follow-up of 36 months were recruited. Pain relief, medications, sensory disturbances, rate and time of pain recurrence were prospectively analyzed. The parameters included: Median follow-up 52.4 months; median dose 75 Gy; median target length 5.7-mm; median target volume 40 mm3; median prescription dose 60 Gy (80% isodose line). Actuarial pain control rate (Barrow Neurological Institute [BNI] class I-IIIa) at 6, 12, 24, and 36 months were 93.5%, 85.8%, 79.7%, and 76%, respectively. Overall, 33 patients (24%) required a second treatment. Overall, 18.1% developed sensory disturbances after 16.4 ± 8.7 months. One patient (0.7%) developed BNI grade IV dysfunction; 6 (4.3%) developed BNI grade III (somewhat bothersome) hypoesthesia after retreatment; BNI grade II (not bothersome) hypoesthesia was reported by 18 patients (11 after retreatment). Shorter nerve length (<6 mm vs 6 mm), smaller nerve volume (<30 mm3 vs >30 mm3), and lower prescription dose (<58 vs > 58 Gy) were associated with treatment failure (P = 0.01, P = 0.02, P = .03, respectively). Re-irradiation independently predicted sensory disturbance (P < .001). Targeting a 6-mm segment of the trigeminal nerve with a prescribed dose of 60 Gy appears safe and effective. Persistent pain control was achieved in most patients with an acceptable risk of sensory complications, which were typically found after re-irradiation. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Zheng MX, et al. Trial of contralateral seventh cervical nerve transfer for spastic arm paralysis. N Engl J Med 2018;378:22-34. Spastic limb paralysis due to injury to a cerebral hemisphere can cause long-term disability. The authors investigated the effect of grafting the contralateral C7 nerve from the non-paralyzed side to the paralyzed side in patients with spastic arm paralysis due to chronic cerebral injury. They randomly assigned 36 patients who had suffered a unilateral arm paralysis for more than 5 years to undergo a C7 nerve transfer with rehabilitation (18 patients) or to undergo rehabilitation alone (18 patients). The primary outcome was the change from baseline to month 12 in the total score on the Fugl–Meyer upper-extremity scale (scores range from 0 to 66, with higher scores indicating a better function). The mean increase in Fugl–Meyer score in the paralyzed arm was 17.7 in the surgery group and 2.6 in the control group (difference, 15.1; 95% confidence interval, 12.2 to 17.9; P < 0.001). With regard to improvement in spasticity as measured on the Modified Ashworth Scale, the smallest between-group difference was in the thumb, with 6, 9, and 3 patients in the surgery group having a 2-unit improvement, a 1-unit improvement, or no change, respectively, as compared with 1, 6, and 7 patients in the control group (P = 0.02). Transcranial magnetic stimulation and functional imaging showed connectivity between the ipsilateral hemisphere and the paralyzed arm. There were no significant differences from baseline to month 12 in power, tactile threshold, or two-point discrimination in the hand on the side of the donor graft. In this single-center trial involving patients who had suffered a unilateral arm paralysis due to chronic cerebral injury for more than 5 years, transfer of the C7 nerve from the non-paralyzed side to the side of the arm that was paralyzed was associated with a greater improvement in function and reduction of spasticity than rehabilitation alone over a period of 12 months. Physiological connectivity developed between the ipsilateral cerebral hemisphere and the paralyzed hand. Contributed by Drs. Madhav V. Kulkarni, Divesh Thaploo, Nagesh C. Shanbhag, Dhananjaya I. Bhat Lee DY, et al. Comparison between subjective scoring and computer-based asymmetry assessment in facial nerve palsy. J Audiol Otol 2018. doi: 10.7874/jao. 2018.00318. This study aimed to assess the feasibility of a personal computer (PC)-based facial asymmetry assessment program (PC-FAAP) and to compare the results of PC-FAAP with subjective regional scoring by raters in acute unilateral peripheral facial nerve paralysis (FNP). For this, the participants were divided into 3 groups (8 participants per group): group I, normal; group II, mild-to-moderate FNP; and group III, severe FNP. Using the PC-FAAP, the mouth asymmetry ratio (MAR), eyebrow asymmetry ratio (EAR), and complete eye closure asymmetry ratio (CAR) were calculated by comparing the movement of tracking points on both the sides. The FNP grading scale (FGS) integrated each score, and the scores were weighted with a ratio of 5:3:2 (MAR: CAR: EAR). The subjective regional scoring was measured on a 0-100 scale score by three otologists. The PC-FAAP and subjective scorings were compared in each group with regard to the consistency of results. The mean scores of the MAR, EAR, CAR, and FGS of each group were significantly different. The PC-FAAP showed significant differences between the three groups in terms of MAR, EAC, CAR, and FGS. The PC-FAAP showed more consistent results than subjective assessment (P < 0.001). The PC-FAAP was significantly more consistent in group I and group III (P < 0.001 and P = 0.002, respectively). The FGS in group III was the only parameter that showed a more consistent result in PC-FAAP than the subjective scoring (P = 0.008). Thus, the authors recommended the use of a PC based FAAP, especially for more severe lesions. Contributed by Dr Kuntal K. Das Karsy M, et al. Trends and cost analysis of upper-extremity nerve injury using the national inpatient sample. World Neurosurg 2018. doi: 10.1016/j.wneu. 2018.11.192. This study was an attempt to calculate an updated incidence of upper-extremity peripheral nerve injury (PNI) in the U.S. and examine clinical trends and costs using one national database. For this purpose, the authors utilized the patients included in the National Inpatient Sample with upper-extremity PNI (International Code of Disease [ICD] 9534, 9550-9559) in 2001-2013. Their analysis showed that a total of 170,579 patients experienced upper-extremity PNI, representing a mean incidence of 43.8/1,000,000 people annually. The mean (±standard error of mean [SEM]) age of these patients was 38.1 ± 0.05 years; 74.3% of patients were males, and 49.0% were Caucasians. PNIs occurred to the ulnar (17.8%), radial (15.1%), digital (18.0%), median (13.0%), multiple (11.5%), and other (10.1%) nerves and the brachial plexus (14.5%). The number of upper-extremity PNIs had an overall decreased incidence. The average care charge was $47,004 ± 185, with an average increase of $4,623/year and the compound annual growth rate of 9.59%. Although surgical nerve repair and home disposition were common with isolated PNIs, patients with brachial plexus PNIs did not have nerve surgery and were more likely to discharge to skilled nursing facilities. Multivariate analysis showed that the length of stay (β = 0.677, P = 0.0001) and number of procedures (β = 0.188, P = 0.0001) most affected total patient charges. These results suggested an overall decrease in the number of PNIs, however, the cost of care had shown an increasing trend. Despite recent advances in nerve repair techniques, the incidence rates of performing nerve surgery have not increased, especially for brachial plexus injuries. This may be an indicator that these types of injuries are still being undertreated. Contributed by Dr Kuntal K. Das Abdou SA, et al. Fusogens: Chemical agents that can rapidly restore function after nerve injury. J Surg Res 2019;233:36-40. This review article sought to highlight fusogens, a group of chemical agents which allow axonal membrane fusion, for their potential use after peripheral nerve injury to restore functions. Chemical fusogens achieve cell fusion by one of the two ways: bringing cells in close enough proximity to each other so that the inherent fluidity of the phospholipid membrane allows for their rearrangement; or, modifying the surface charges of the membranes to diminish repellent charges. These agents have been studied in different extents in protoplasts, animals, and humans. The aim was to propose a unifying system for classifying fusogens to better understand their role in cell fusion. They reviewed the most commonly cited chemical fusogens, their structures, mechanisms of actions, and clinical applications to date, eventually identifying seven chemical fusogens (polyethylene glycol, chitosan, dextran sulfate, n-nonyl bromide, calcium, sodium nitrate, and H-α-7), which have each been studied before. Sowers initially put forth a classification system that identified these agents as cell aggregators and membrane modifiers, respectively. They concluded that the most effective approach to axonal membrane repair was likely a combination of two previously described discrete mechanisms of actions, namely cell aggregation and membrane modification. Contributed by Dr Kuntal K. Das Lovati AB, et al. Nerve repair using decellularized nerve grafts in rat models. A review of the literature. Front Cell Neurosci 2018;12:427. The hunt for a substitute of autologous nerve graft to bridge the nerve gap seems far from over. This study reports the results of a systematic review of the literature published between January 2007 and October 2017. The aim was to quantitatively analyze the effectiveness of decellularized nerve grafts in rat experimental models. The review included 33 studies in which eight different decellularization protocols were described. The decellularized nerve grafts were reported to be immunologically safe and able to support both functional and morphological regeneration after nerve injury. Chemical protocols were found to be superior to physical protocols. However, the authors admitted that further research was needed to optimize preparation protocols (including recellularization), improve their effectiveness, and substitute the current gold standard (the autologous nerve grafts), especially in the repair of long nerve defects. Contributed by Dr Kuntal K. Das Well L, et al. Differentiation of peripheral nerve sheath tumors in patients with neurofibromatosis type 1 using diffusion-weighted magnetic resonance imaging. Neuro Oncol 2018 doi: 10.1093/neuonc/noy199. [Epub ahead of print] The authors aimed to determine the value of diffusion-weighted (DW) magnetic resonance imaging (MRI) for characterization of benign and malignant peripheral nerve sheath tumors (PNSTs) in patients with neurofibromatosis type 1 (NF1). For this, twenty-six patients with NF1 and suspicion of malignant transformation of PNSTs were prospectively enrolled, and subjected to DW MRI in a 3 Tesla MR machine. For a set of benign (n = 55) and malignant (n = 12) PNSTs, functional MRI parameters were derived from both biexponential intravoxel incoherent motion (diffusion coefficient D and perfusion fraction f) and monoexponential data analysis (apparent diffusion coefficients [ADCs]). A panel of morphological MRI features was evaluated using T1- and T2-weighted imaging. Mann-Whitney-U test, Fisher's exact test, and receiver operating characteristic (ROC) analyses were applied to assess the diagnostic accuracy of quantitative and qualitative MRI. Cohen's kappa was used to determine inter-rater reliability. Malignant PNSTs demonstrated significantly lower diffusivity (P < 0.0001) compared to benign PNSTs. The perfusion fraction f was significantly higher in malignant PNSTs (P < 0.001). In receiver operating characteristic curve analysis, the functional MRI parameters showed a high diagnostic accuracy for differentiation of PNSTs. By contrast, the morphological imaging features had only limited sensitivity (18-94%) and specificity (18-82%) for identification of the malignancy. The inter-rater reliability was higher for monoexponential data analysis. Therefore, the authors concluded that DW imaging was a better diagnostic sequence than the conventional sequences in allowing an accurate differentiation of benign and malignant peripheral nerve sheath tumors in NF1. Contributed by Dr Kuntal K. Das Gul BU, et al. Silicone-based simulation models for peripheral nerve microsurgery. J Plast Reconstr Aesthet Surg 2018 doi: 10.1016/j.bjps. 2018.10.025. In this paper, the authors propose a silicone based peripheral nerve model, utilizing several formulations of silicone. The design and fabrication of the model realized the hierarchical structure of peripheral nerves. The mechanical properties of this model were characterized via the Universal Testing Machine; the damage caused by the needle on the entry sites was assessed through scanning electron microscopy (SEM). A formulation with 83.3 wt% silicone oil and 0.1 wt% cotton fiber was chosen to be used as nerve fascicles. Both 83.3 wt% silicone oil with cotton fiber and 66.6 wt% silicone oil without fiber provided a microsuturing response similar to that of epineurium at a wall thickness of 1 mm. The SEM also confirmed that the entry of the needle did not introduce significant holes at the microsuturing sites. The proposed peripheral nerve model mimicked human tissues mechanically and cosmetically, and a simulation of the repair of a fifth-degree nerve injury was achieved. The authors claimed that the proposed model could provide a platform for improving the technical skills of surgical trainees prior to their practice on cadaver/animal models. In addition, they believe that this model has the potential to serve as a standardized test medium for assessing the skill sets of surgeons. Contributed by Dr Kuntal K. Das Cui S, et al. The effect of re-neurorrhaphy of the distal co-aptation on nerve regeneration after nerve grafting: An animal experimental study. World Neurosurg 2018 doi: 10.1016/j.wneu. 2018.11.049. With the previous studies demonstrating positive results of re-neurorrhaphy of a distal co-aptation at an appropriate time after nerve grafting in terms of upregulating neurotrophins in rat spinal cord neurons, the authors conducted the present study with the aim to evaluate the effect of this procedure on peripheral nerve regeneration. Fifteen Wistar rats were randomly assigned to sham-surgery, control, or experimental (transection and re-repair of the distal coaptation of the grafting nerve) groups. The sciatic nerve was evaluated via electromyogram (EMG) and histology at 20 weeks. When crossing the proximal coaptation of the grafting nerve, the EMG and histological evaluations did not significantly differ between the experimental and control groups (P > 0.05). In contrast, crossing the distal coaptation yielded significantly better values (P < 0.05) in the experimental group. These results indicate that re-neurorrhaphy of the distal coaptation at an appropriate time after nerve grafting could improve nerve function and facilitate axonal regeneration. Contributed by Dr Kuntal K. Das
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