Dutch injection versus surgery trial in patients with carpal tunnel syndrome (DISTRICTS): protocol of a randomised controlled trial comparing two treatment strategies.

INTRODUCTION: Carpal tunnel syndrome (CTS) is the most common peripheral neuropathy. The optimal treatment strategy is still unknown. The objective of the Dutch Injection versus Surgery TRIal in patients with CTS (DISTRICTS) is to investigate if initial surgery of CTS results in a better clinical outcome and is more cost-effective when compared with initial treatment with corticosteroid injection. METHODS AND ANALYSIS: The DISTRICTS is an ongoing multicenter, open-label randomised controlled trial. Participants with CTS are randomised to treatment with surgery or with a corticosteroid injection. If needed, any additional treatments after this first treatment are allowed and these are not dictated by the study protocol. The primary outcome is the difference between the groups in the proportion of participants recovered at 18 months. Recovery is defined as having no or mild symptoms as measured with the 6-item carpal tunnel symptoms scale. Secondary outcome measurements are among others: time to recovery, hand function, patient satisfaction, quality of life, additional treatments, adverse events, and use of care and health-related costs. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethical Committee of the Amsterdam University Medical Centers (study number 2017-171). Study results will be disseminated in peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: ISRCTN Registry: 13164336.

Sensitivity of magnetoencephalography as a diagnostic tool for epilepsy: a prospective study.

The diagnostic process for epilepsy can be lengthy and stressful, which may delay the start of treatment. The objective of this study was to determine the benefit of routine magnetoencephalography (MEG) with regard to diagnostic gain, compared to routine electroencephalography (EEG), EEG following sleep deprivation (EEGsd), and 24-hour EEG. In this prospective study, patients were included from two centres (Academic Centre for Epileptology Kempenhaeghe, Heeze and Elisabeth-Twee Steden Hospital, Tilburg) and MEG recording took place at a single centre (Amsterdam University Medical Centre, Vrije Universiteit Amsterdam) in The Netherlands. Consecutively referred patients from peripheral hospitals were included between August 2013 and March 2016. Patients were offered routine MEG in addition to EEG examination and MRI for the diagnosis of epilepsy. The final clinical diagnosis was based on all available clinical data and test results at the end of the diagnostic process. Sensitivity, specificity, and positive and negative predictive values were calculated for routine EEG, routine EEG plus additional EEG and MEG. In addition, diagnostic gain associated with MEG, relative to the other modalities, was calculated. Secondary outcome was congruence of localization of epileptiform discharges between MEG and MRI or final clinical diagnosis. Based on a cohort of 138 patients, sensitivity and specificity was shown to be 31.6% and 78.4% for routine MEG, 31.6% and 100% for routine EEG, and 52.6% and 97.3% for routine EEG plus additional EEG, respectively. Routine MEG demonstrated a diagnostic gain of 16.8% compared to routine EEG and 9.5% compared to routine EEG plus additional EEG. In 35.7% of patients with a lesion on MRI that was consistent with the final clinical diagnosis, MEG showed epileptiform discharges in the same area. Routine MEG may provide additional value during the initial diagnosis of epilepsy.

Nerve ultrasound shows subclinical peripheral nerve involvement in neurofibromatosis type 2.

INTRODUCTION: Neurofibromatosis type 2 (NF2) is mainly associated with central nervous system (CNS) tumors. Peripheral nerve involvement is described in symptomatic patients, but evidence of subclinical peripheral nerve involvement is scarce. METHODS: We conducted a cross-sectional pilot study in 2 asymptomatic and 3 minimally symptomatic patients with NF2 to detect subclinical peripheral nerve involvement. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS). RESULTS: A total of 30 schwannomas were found, divided over 20 nerve segments (33.9% of all investigated nerve segments). All patients had at least 1 schwannoma. Schwannomas were identified with HRUS in 37% of clinically unaffected nerve segments and 50% of nerve segments with normal NCS findings. DISCUSSION: HRUS shows frequent subclinical peripheral nerve involvement in NF2. Clinicians should consider peripheral nerve involvement as a cause of weakness and sensory loss in the extremities in patients with this disease. Muscle Nerve 57: 312-316, 2018.

Nerve ultrasound in neurofibromatosis type 1: A follow-up study.

OBJECTIVE: To investigate development of sonographic abnormalities and applications of high-resolution ultrasonography (HRUS) in neurofibromatosis type 1 (NF1). METHODS: Sixteen asymptomatic or minimally symptomatic NF1 patients underwent HRUS at inclusion and 1 year follow-up. Upper and lower extremity nerves were investigated. Peripheral nerve involvement was graded. RESULTS: Plexiform neurofibromas (PNFs) were found in 7 patients (43.8%) at inclusion and 10 (62.5%) at follow-up. All initially identified PNFs were also found at follow-up; additional PNFs were found by extended longitudinal assessment at follow-up. All 3 patients with minor and 7 patients with severe peripheral nerve involvement had similar involvement at follow-up. Mean nerve size change was -0.2 mm2 (±1.6) and 0.3 mm2 (±6.2) in patients with minor and severe involvement. Mean PNF size change was -0.1 mm2 (±9.9). CONCLUSIONS: HRUS allows qualitative assessment of peripheral nerves, which makes it advantageous as initial imaging technique in suspected neuropathy. Patients with minimal nerve involvement remained so, and might therefore require less follow-up for malignant peripheral nerve sheath tumor (MPNSTs) development. Measured change in PNF size was highly variable. Repeating an extensive standardized HRUS protocol during follow-up thus seems less useful to screen for MPNSTs. SIGNIFICANCE: HRUS has potential applications as diagnostic and screening tool in NF1.

Nerve ultrasound: A useful screening tool for peripheral nerve sheath tumors in NF1?

OBJECTIVE: To determine ultrasonographic peripheral nerve involvement in patients with asymptomatic neurofibromatosis type 1 (NF1). METHODS: Thirteen asymptomatic and 4 minimally symptomatic patients with NF1 were included in this cross-sectional pilot study to detect asymptomatic abnormalities of the brachial plexus and upper and lower extremity nerves. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS). RESULTS: HRUS showed abnormalities in 16 patients (94.1%). Neurofibromas were identified in 10 patients (58.8%): localized neurofibromas were found in 3 patients (17.6%), plexiform neurofibromas in 3 (17.6%), and both in 4 (23.5%). In 6 patients (35.3%), only nerve enlargement without an abnormal fascicular pattern was observed. Severe involvement of the peripheral nervous system with multiple plexiform neurofibromas was observed in 7 patients (41.2%), while 4 patients (23.5%) had no or only minor involvement. Both NCS and HRUS were performed on 73 individual nerve segments. In 5.5%, abnormalities were found with both tests; in 50.7%, only with HRUS; and in 1.4%, only with NCS. CONCLUSIONS: HRUS frequently showed subclinical involvement of the peripheral nerves in NF1, also when NCS were normal. HRUS findings ranged from normal to widespread peripheral nerve involvement. Because the presence of plexiform neurofibromas and the benign tumor load are risk factors for the development of a malignant peripheral nerve sheath tumor, HRUS may be a useful tool to identify a subgroup of patients who could benefit from regular follow-up.

Quantitative assessment of nerve echogenicity as an additional tool for evaluation of common fibular neuropathy.

OBJECTIVE: Quantitative assessment of nerve echogenicity using the MaxEntropy, RenyiEntropy and Yen methods has shown promise in the assessment of ulnar neuropathy at the elbow. The purpose of this study was to determine the clinical usefulness of quantitative echogenicity measurement when using these three automatic thresholding methods in the evaluation of patients with common fibular (CF) neuropathy. METHODS: High-resolution ultrasonography (HRUS) images of the CF nerve from 45 patients with CF neuropathy were compared to 42 healthy controls. RESULTS: With all three methods patients with CF neuropathy had significantly higher mean hypoechoic fraction than healthy controls at the level of the fibular head (FH): MaxEntropy 87.4% versus 71.9% (p<0.001), RenyiEntropy 84.7% versus 68% (p<0.001) and Yen 87.6% versus 68.2% (p<0.001). Patients with CF neuropathy could be differentiated from healthy controls at a hypoechoic fraction cut-off point of 82% (MaxEntropy), 80% (RenyiEntropy) and 80% (Yen) with a sensitivity of 82%, 82% and 84% respectively, and a specificity of 93%, 95% and 83% respectively. Similar results were found for sonographic measurements above the FH. CONCLUSION: Quantitative assessment of nerve echogenicity using the MaxEntropy, RenyiEntropy and Yen methods can be used to distinguish between patients with CF neuropathy and healthy controls with high sensitivity and specificity. SIGNIFICANCE: These three proven automatic thresholding methods can be used to assess nerve echogenicity in future studies. Quantitative echogenicity assessment with HRUS shows promise for the future as a potential diagnostic tool in daily clinical practice.

The EEG as a diagnostic tool in distinguishing between dementia with Lewy bodies and Alzheimer's disease.

OBJECTIVE: Current diagnostic criteria for dementia with Lewy bodies (DLB) regard electroencephalogram (EEG) abnormalities as a supportive feature. It has also been suggested that EEG abnormalities in DLB are more extensive than in Alzheimer's disease (AD). Still, the use of qualitative EEG analysis as a diagnostic tool to distinguish between DLB and AD remains rare in daily clinical practice because of conflicting studies and absence of a reliable scoring method. The Grand Total EEG (GTE) score has been used in one study to differentiate DLB from AD with good sensitivity and specificity (Roks et al., 2008). METHODS: EEGs from 29 patients with DLB and 54 with AD were visually rated according to the GTE score. RESULTS: Patients with DLB had significantly higher median scores than patients with AD: 9 vs. 4. Patients with DLB could be distinguished from those with AD at a GTE cut-off score of 6.5 with a sensitivity of 79% and a specificity of 76%. The association between GTE and DLB was independent of age, gender, Mini Mental State Examination and use of medication. Frontal intermittent rhythmic delta activity (FIRDA) was found in 17.2% of patients with DLB compared to 1.8% with AD. Except for the lower cut-off score our results are comparable to the previous study on the GTE score. CONCLUSION: The GTE score has proven to be a reliable and simple scoring method applicable to daily clinical practice. Qualitative EEG analysis can help to differentiate DLB from AD with good sensitivity and specificity. SIGNIFICANCE: EEG should play a more prominent role in daily clinical practice as a diagnostic tool in differentiating DLB from AD. Future revisions of the diagnostic criteria for DLB should consider the other EEG abnormalities as mentioned in the GTE score, especially FIRDA.

Distinctive patterns of sonographic nerve enlargement in Charcot-Marie-Tooth type 1A and hereditary neuropathy with pressure palsies.

OBJECTIVE: The extent of sonomorphologic differences of peripheral nerves between CMT and HNPP is unknown. METHODS: We recruited 9 patients with CMT-1A and 9 with HNPP. Patients underwent a standardized sonographic protocol, which evaluated nerve size and vascularization. We quantitatively assessed fascicle size and echogenicity. RESULTS: All 18 patients demonstrated nerve enlargement, but no increased vascularization. HNPP demonstrated larger nerves at sites of entrapment (median nerve at the carpal tunnel p=0.049, ulnar nerve at the sulcus p<0.001), greater swelling ratios of median (p<0.001), ulnar (p=0.017) and fibular nerve (p=0.005) than CMT-1A. CMT-1A revealed larger nerves proximal to sites of entrapment (median and fibular nerve, brachial plexus p<0.001). Nerve fascicles where larger (p<0.001) and more hypo-echogenic in CMT-1A. Nerve, fascicle size nor echogenicity correlated with age, gender or MRC sum-score. CONCLUSIONS: Ultrasonography of nerves reveals specific phenotypes differentiating CMT-1A from HNPP. In CMT-1A enlargement of nerves and fascicles is multifocal among multiple nerves, whereas in HNPP nerve enlargement is restricted to sites of entrapment. SIGNIFICANCE: Our findings of specific sonomorphological phenotypes, differentiating CMT-1A from HNPP, may help to improve our pathophysiological insights in CMT and HNPP.

Diagnostic value of high-resolution sonography in common fibular neuropathy at the fibular head.

INTRODUCTION: In 30% of patients with common fibular (CF) neuropathy at the fibular head, reliable localization of the site of the lesion by means of electrodiagnostic testing is challenging. METHODS: We prospectively assessed proximal CF nerve cross-sectional area (CSA) measurements and at the fibular head in 87 patients with CF neuropathy and 16 with a different condition. Reference values were obtained in 64 healthy volunteers. RESULTS: Patients with CF neuropathy had a significantly larger CF nerve CSA than controls and patient controls (P < 0.0001). Sonography localized the lesion at the fibular head in 55% and just above it in 71% of patients. Assessment of the most thickened part of the CF nerve resulted in a cut-off value of >8 mm² with a sensitivity of 90% (CI 81-95%) and a specificity of 69% (CI 58-78%). CONCLUSION: High-resolution sonography in addition to electrodiagnostic testing improves diagnostic reliability in CF neuropathy.

Piso-hamate hiatus syndrome in a patient with Riche-Cannieu anastomosis.

Various nerve anastomoses and anatomic variants in the nervous system have been described. It is important to be familiar with these anastomoses because they can mimic several clinical conditions, possibly leading to misdiagnosis. We report the case of a patient who experienced progressive loss of strength in his left hand without sensory complaints. On neurological examination atrophy was seen in the thenar and first dorsal interosseous muscles of the left hand. Serial electrophysiological studies ruled out motor neuron disease. Electromyography and nerve conduction studies revealed a Riche-Cannieu anastomosis in the left hand. In combination with piso-hamate hiatus syndrome, this anastomosis explained the clinical condition of the patient. It is important to be aware of this anastomosis and this syndrome because it can mimic motor neuron disease.

Increased nerve vascularization detected by color Doppler sonography in patients with ulnar neuropathy at the elbow indicates axonal damage.

INTRODUCTION: The aim of this study was to establish the prevalence of increased intraneural vascularization detected by ultrasonography (IVUS) in patients with ulnar neuropathy at the elbow (UNE) and to determine its relationship to clinical, ultrasonographic, and electrodiagnostic findings. METHODS: High-resolution ultrasonography and color Doppler imaging were performed in 137 patients with confirmed UNE, 24 patient controls, and 70 healthy controls (HCs). RESULTS: IVUS was found in 21 (15%) of 137 patients with UNE, in 1 (4%) of 24 patient controls, and in 0 of 70 HCs (P = 0.001). Patients with IVUS were more likely to have severe weakness (P = 0.01), severe atrophy of ulnar-innervated muscles (P = 0.008), axonal damage (P = 0.001), and more pronounced nerve enlargement (P = 0.03) than those without IVUS. CONCLUSIONS: IVUS in the ulnar nerve can be detected in patients with UNE and is associated with nerve enlargement and clinical and electrodiagnostic severity. In addition, IVUS is associated with axonal damage.

Rhythmic heart beat artefacts mimicking an ictal EEG pattern with abundant interictal epileptiform activity in both mother and child.

We present the EEG findings in a two-year-old girl with cryptogenic localisation-related epilepsy. The electroencephalogram showed fronto-temporal spike-wave discharges. In addition, the EEG repeatedly showed activity at different electrodes consisting of spikes with varying amplitude, rhythmicity and frequency, mimicking polyspikes. Both low- and high-amplitude spikes were generated from the same electrodes, however, only the low-amplitude spikes coincided with features of the child's electrocardiogram. Video monitoring showed the child's head resting on her mother's chest. This spike pattern was shown to be a heart beat artefact originating from the mother, as implied by the rhythmicity and the shift to other electrodes by moving the child's head, causing electrocardiogram artefacts on the posterior electrodes. This case study underscores the importance of routine use of simultaneous electroencephalogram and video monitoring. [Published with video sequences].

Effect of intracranial pressure monitoring and targeted intensive care on functional outcome after severe head injury.

OBJECTIVE: : Intracranial hypertension after severe head injury is associated with case fatality, but there is no sound evidence that monitoring of intracranial pressure (ICP) and targeted management of cerebral perfusion pressure (CPP) improve outcome, despite widespread recommendation by experts in the field. The purpose was to determine the effect of ICP/CPP-targeted intensive care on functional outcome and therapy intensity levels after severe head injury. DESIGN: : Retrospective cohort study with prospective assessment of outcome. SETTING: : Two level I trauma centers in The Netherlands from 1996 to 2001. PATIENTS: : Three hundred thirty-three patients who had survived and remained comatose for >24 hrs, from a total of 685 consecutive severely head-injured adults. INTERVENTIONS: : In center A (supportive intensive care), mean arterial pressure was maintained at approximately 90 mm Hg, and therapeutic interventions were based on clinical observations and computed tomography findings. In center B (ICP/CPP-targeted intensive care), management was aimed at maintaining ICP <20 mm Hg and CPP >70 mm Hg. Allocation to either trauma center was solely based on the site of the accident. MEASUREMENTS AND MAIN RESULTS: : We measured extended Glasgow Outcome Scale after >/=12 months. Patient characteristics were well balanced between the centers. ICP monitoring was used in zero of 122 (0%) and 142 of 211 (67%) patients in centers A and B, respectively. In-hospital mortality rate was 41 (34%) vs. 69 (33%; p = .87). The odds ratio for a more favorable functional outcome following ICP/CPP-targeted therapy was 0.95 (95% confidence interval, 0.62-1.44). This result remained after adjustment for potential confounders. Sedatives, vasopressors, mannitol, and barbiturates were much more frequently used in center B (all p < .01). The median number of days on ventilator support in survivors was 5 (25th-75th percentile, 2-9) in center A vs. 12 (7-19) in center B (p < .001). CONCLUSIONS: : ICP/CPP-targeted intensive care results in prolonged mechanical ventilation and increased levels of therapy intensity, without evidence for improved outcome in patients who survive beyond 24 hrs following severe head injury.