Fully Automatic, Semiautomatic, and Manual Corneal Nerve Fiber Analysis in Patients With Sarcoidosis.

Purpose: No guidelines are available on the preferred method for analyzing corneal confocal microscopy (CCM) data. Manual, semiautomatic, and automatic analyzes are all currently in use. The purpose of the present study was threefold. First, we aimed to investigate the different methods for CCM analysis in patients with and without small fiber neuropathy (SFN). Second, to determine the correlation of different methods for measuring corneal nerve fiber length (CNFL) and nerve fiber area (NFA). Finally, we investigated the added value of automatic NFA analysis. Methods: We included 20 healthy controls and 80 patients with sarcoidosis, 31 with established SFN and 49 without SFN. The CNFL was measured using CCMetrics, ACCMetrics, and NeuronJ. NFA was measured with NFA FIJI and ACCMetrics NFA. Results: CNFL and NFA could not distinguish sarcoidosis with and without SFN or healthy controls. CCMetrics, NeuronJ, and ACCMetrics CNFL highly correlated. Also, NFA FIJI and ACCMetrics NFA highly correlated. Reproducing a nonlinear formula between CNFL and NFA confirmed the quadratic relation between NFA FIJI and ACCMetrics CNFL. CCMetrics and NeuronJ instead showed a square root relationship and seem to be less comparable owing to differences between automatic and manual techniques. Conclusions: ACCMetrics can be used for fully automatic analysis of CCM images to optimize efficiency. However, CNFL and NFA do not seem to have a discriminatory value for SFN in sarcoidosis. Further research is needed to determine the added value and normative values of NFA in CCM analysis. Translational Relevance: Our study improves the knowledge about CCM software and pathophysiology of SFN.

Thermal threshold testing: call for a balance between the number of measurements and abnormalities in the diagnosis of sarcoidosis-associated small fiber neuropathy.

Introduction: Several recent studies of diagnosing small fiber neuropathy (SFN) have shown a lack of uniformity in thermal threshold testing (TTT) or quantitative sensory testing (QST) which makes it a challenge to compare the data. It is known that the chance of finding an abnormality increases with increasing number of measurements. Objectives: With this study, we first wanted to investigate whether TTT could benefit from a new approach focusing on the balance between the number of measurements, depending on the selection of parameters and measuring sites, and on number of abnormalities (NOAs). Second, we wanted to address the role of the method of levels (MLe) in possible desensitization during TTT measurements. Methods: One hundred seventeen participants were included (48 patients with sarcoidosis with probable SFN, 49 without SFN, and 20 healthy controls). Thermal threshold testing measurements and Small Fiber Neuropathy Screening List (SFNSL) questionnaire were used to assess SFN. Results: A combination of measuring all thermal threshold parameters at both feet except for MLe showed the best diagnostic performance. Increasing TTT NOAs correlates with the severity of SFN. Adding the SFNSL questionnaire further improves diagnostic performance. Discussion: Looking at TTT NOAs in all TTT parameters except for MLe at both feet should be considered as a new approach to improve the consistency and balance between the selection of TTT parameters, measuring sites, and definition of "abnormal QST." Moreover, the SFNSL questionnaire is a valuable tool to quantify SFN symptoms and could improve SFN diagnosis.

Can novel non-invasive autonomic tests help discriminate between pure autonomic failure and multiple system atrophy?

BACKGROUND: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are rare disorders causing severe autonomic failure. Their initially similar clinical presentation may lead to years of diagnostic difficulties. Improving the differentiation would have an important impact on patients and families in view of better prediction of disease progression. OBJECTIVE: To investigate whether several new non-invasive autonomic tests are beneficial in discriminating between PAF and MSA. METHODS: Patients and controls underwent two tests examining the autonomic innervation of the skin (Sudoscan and water-induced skin wrinkling) and one test measuring retinal nerve fiber layer thickness in the eye. RESULTS: The skin vasomotor tests yielded differences between the disease and control groups, but did not discriminate between PAF and MSA. No differences in retinal nerve fiber layer thickness were found between the groups. CONCLUSION: The tests applied in this study may help to confirm autonomic failure but did not support the differential diagnosis between PAF and MSA.

Outcome of Carpal Tunnel Release and the Relation With Depression.

PURPOSE: To examine the relation between depressive symptoms and outcome of carpal tunnel release (CTR). METHODS: Prospective study in a general hospital with data collection at baseline and 3 and 12 months after CTR. We quantified depressive symptoms using the Center for Epidemiologic Studies Depression (CES-D) scale and performed multivariable analyses on 2 outcome measures: (1) carpal tunnel syndrome (CTS) symptoms (Boston Carpal Tunnel Questionnaire [BCTQ]) and (2) palmar pain, focusing on preoperative CES-D and BCTQ score, sex, age, alcohol use, diabetes, and severity of nerve conduction abnormalities. RESULTS: We included 227 patients. Before surgery, patients with depression had a higher BCTQ score than patients without depression. After 1 year, depressed patients had a higher BCTQ score and more palmar pain. The CES-D decreased by a median of 2 points from baseline to 1 year. This correlated with the decrease in BCTQ score. Multivariable analyses showed that preoperative depression had a small but statistically significant influence on palmar pain, but not on postoperative BCTQ score. CONCLUSIONS: Depression is not an independent predictor of residual CTS symptoms 1 year after CTR. Depressive symptoms in patients with CTS decrease after CTR, along with a decrease in CTS symptoms. The nature of this relationship is unknown. Patients with CTS and depression may expect a somewhat higher degree of palmar pain after CTR, the clinical relevance of which is small. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Anterior subcutaneous transposition for persistent ulnar neuropathy after neurolysis.

OBJECTIVE Little is known about optimal treatment if neurolysis for ulnar nerve entrapment at the elbow fails. The authors evaluated the clinical outcome of patients who underwent anterior subcutaneous transposition after failure of neurolysis of ulnar nerve entrapment (ASTAFNUE). METHODS A consecutive series of patients who underwent ASTAFNUE performed by a single surgeon between 2009 and 2014 was analyzed retrospectively. Preoperative and postoperative complaints in the following 3 clinical modalities were compared: pain and/or tingling, weakness, and numbness. Six-point satisfaction scores were determined on the basis of data from systematic telephonic surveys. RESULTS Twenty-six patients were included. The median age was 56 years (range 22-79 years). The median duration of complaints before ASTAFNUE was 23 months (range 8-78 months). The median interval between neurolysis and ASTAFNUE was 11 months (range 5-34 months). At presentation, 88% of the patients were experiencing pain and/or tingling, 46% had weakness, and 50% had numbness of the fourth and fifth fingers. Pain and/or tingling improved in 35%, motor function in 23%, and sensory disturbances in 19% of all the patients. Improvement in at least 1 of the 3 clinical modalities was found in 58%. However, a deterioration in 1 of the 3 modalities was noted in 46% of the patients. On the patient-satisfaction scale, 62% reported a good or excellent outcome. Patients with a good/excellent outcome were a median of 11 years younger than patients with a fair/poor outcome. No other factor was significantly related to satisfaction score. CONCLUSIONS A majority of the patients were satisfied after ASTAFNUE, even though their symptoms only partly resolved or even deteriorated. Older age is a risk factor for a poor outcome. Other factors that affect outcome might play a role, but they remain unidentified. One of these factors might be earlier surgical intervention. The modest results of ASTAFNUE should be mentioned when counseling patients after failure of neurolysis of ulnar nerve entrapment to manage their expectations. Patients, especially those who are elderly, might even consider not undergoing a secondary procedure. A randomized trial that includes a conservative treatment group and groups undergoing one of the several possible surgical procedures is needed to find the definitive answer for this clinical problem.

Decompressive Surgery for Diabetic Neuropathy: Waiting for Incontrovertible Proof.

: Triple decompression surgery has been advocated as a treatment for diabetic peripheral neuropathy (DPN). A practice advisory published in 2006 by the American Academy of Neurology concluded that "this treatment alternative should be considered unproven." Since then, multiple cohort studies involving several thousands of patients and 1 nonblind, randomized, controlled trial have been published, suggesting that surgical treatment of DPN has become commonplace in many centers globally. The results of these observational studies suggest that decompressive surgery could result in a substantial reduction of pain and the restoration of sensation in patients with DPN. However, as these studies are all observational in design, the utility of surgery remains unproven. Furthermore, the selection of patients for surgery is based on the incorrect assumption that the presence of a Tinel sign at sites of potential entrapment indicates nerve compression. The utility of surgery could be determined through a randomized, double-blind, sham-controlled trial in which 1 leg is treated with surgical decompression and the other with sham surgery. This design would eliminate a large number of possible confounders and would therefore require only a small number of patients. Such a trial is currently being performed at the University of Texas. The true beneficiaries will be patients with DPN: either decompressive surgery will be established as an evidence-based treatment for millions of patients or they will be spared from potentially harmful surgery with no significant benefit. ABBREVIATION: DPN, diabetic peripheral neuropathy.

The Tinel sign has no diagnostic value for nerve entrapment or neuropathy in the legs.

INTRODUCTION: The presence of a Tinel sign in leg nerves has been proposed as a criterion for decompressive surgery in polyneuropathy. We investigated the diagnostic yield of the Tinel sign for nerve entrapment and for distal symmetrical peripheral neuropathy (DSPN). METHODS: We prospectively tested for the Tinel sign at 3 sites of possible nerve entrapment per leg in 91 patients. Entrapment was defined using nerve conduction data. We also investigated whether the number of sites at which the Tinel sign was present identified patients with DSPN. RESULTS: Sensitivity of the Tinel sign for nerve entrapment was low (29%, 44%, and 17%) for the 3 sites, and specificity was moderate (86%, 75%, and 81%). In the subgroup with DSPN, sensitivity was extremely low (0%, 20%, and 8%), and specificity was moderate (91%, 79%, and 73%). The number of sites with a Tinel sign did not identify patients with DSPN. CONCLUSION: The Tinel sign does not reliably indicate nerve entrapment or DSPN. Muscle Nerve 54: 25-30, 2016.

Decompressive surgery in a patient with hyperostosis corticalis generalisata for relief of cognitive disability and dysaesthesia.

A 28-year-old man with genetically confirmed hyperostosis corticalis generalisata (Van Buchem disease) suffered from headache and progressive cognitive and sensibility disorders. Bone formation of the skull was ongoing, leading to narrowing of the intracranial space and foramen magnum. A large bilateral frontoparietal craniotomy and decompression of the foramen magnum resulted in almost complete relief of his symptoms. This is the first report on successful decompressive surgery as a treatment of cognitive impairment and dysaesthesia.

[Neurosarcoidosis and paraneurosarcoidosis: new online registration of patients]. / Neurosarcoïdose en paraneurosarcoïdose: nieuwe onlineregistratie van patiënten.

The clinical spectrum of neurosarcoidosis is highly diverse; virtually any neurological syndrome can present, depending upon granuloma localization. There are indications that neurosarcoidosis is insufficiently recognized as a separate clinical entity. In the absence of major prospective clinical trials, we launched a large national online registry of neurosarcoidosis patients in the Netherlands in June 2014 at www.neurosarcoidose.nl. When a patient with sarcoidosis presents with neurological symptoms that may compatible with sarcoidosis, it is important to locate sites of disease activity accessible for biopsy outside the nervous system. Small nerve fibre neuropathy is a common neurological complication of sarcoidosis. It is considered an epiphenomenon, and therefore classified as 'para-neurosarcoidosis'. Neurological symptoms causing disability are an indication for immunosuppressive therapy. There is increasing evidence for the effective treatment of refractory neurosarcoidosis using biologicals. Whether the intravenous administration of immunoglobulins or ARA290, an erythropoietin derivative with TNF-α-antagonistic and tissue-protective characteristics, is effective for small nerve fibre neuropathy in sarcoidosis is subject for study.

The diagnostic value of water immersion skin wrinkling and Neuropads in small fiber neuropathy.

OBJECTIVE: To investigate the diagnostic yield of two simple tests for small fiber neuropathy (SFN): Neuropads® and water immersion skin wrinkling (WISW). METHODS: We studied 35 patients clinically diagnosed with SFN and 61 age- and sex-matched healthy controls. Wrinkling was judged as absent (abnormal), or present (normal) after immersion of the hands for 30 min. Neuropads are plasters impregnated with cobalt blue that are applied with to the soles of the feet. These remain blue when feet are dry (abnormal) or turn pink when there is some moisture (normal). RESULTS: The sensitivity of the Neuropad was 29% and its specificity 93%. The sensitivity of WISW was 66% and its specificity 70%. Regarding abnormality of at least one test to define the combination as abnormal yielded a sensitivity of 71% and specificity 67%. When both tests had to be abnormal to judge the combination abnormal, sensitivity was 23% and specificity 97%. CONCLUSIONS: The Neuropad has a high specificity, so an abnormal result can be used to confirm SFN. WISW has a moderate sensitivity and specificity. Combining these two tests can be helpful: when both tests are abnormal the diagnosis SFN is highly likely. SIGNIFICANCE: The Neuropad and WISW can be helpful in daily practice by supporting the diagnosis SFN.