Clinical neurophysiology of functional motor disorders: IFCN Handbook Chapter.

Functional Motor Disorders are common and disabling. Clinical diagnosis has moved from one of exclusion of other causes for symptoms to one where positive clinical features on history and examination are used to make a "rule in" diagnosis wherever possible. Clinical neurophysiological assessments have developed increasing importance in assisting with this positive diagnosis, not being used simply to demonstrate normal sensory-motor pathways, but instead to demonstrate specific abnormalities that help to positively diagnose these disorders. Here we provide a practical review of these techniques, their application, interpretation and pitfalls. We also highlight particular areas where such tests are currently lacking in sensitivity and specificity, for example in people with functional dystonia and functional tic-like movements.

Measuring saccades in patients with Niemann-Pick type C: A comparison between video-oculography and a novel eye tracking test based on continuous psychophysics.

Introduction: Vertical supranuclear gaze palsy is a key feature of Niemann-Pick type C (NP-C) and is commonly quantified using video-oculography (VOG). VOG requires sitting still for long times and performing specific tasks, thus it can be challenging or impossible for patients severely affected by movement disorders or cognitive impairment. To overcome this limitation, we measure saccades of NP-C patients using a fast eye tracking test based on continuous psychophysics and compare it to VOG. Methods: Saccades of six NP-C patients and six age-matched controls were assessed using VOG and Standardized Oculomotor and Neuro-ophthalmic Disorders Assessment (SONDA). In SONDA, participants continuously track a semi-randomly moving dot on a computer screen while their gaze is being tracked. For both assessments, saccades were quantified using four conventional measures: amplitude, gain, latency, and peak velocity. Furthermore, SONDA's continuous measures were quantified with several novel spatio-temporal properties. Results: In the NP-C patients, both methods revealed reduced amplitude, gain, peak velocity, and increased latency of vertical saccades compared to horizontal saccades and compared to healthy controls. Effect sizes obtained with SONDA were overall larger than those for VOG. SONDA's spatio-temporal properties showed similar trends. Conclusion: SONDA reveals a deterioration of vertical saccades in NP-C patients that is consistent with VOG. SONDA's measures based on continuous psychophysics are consistent with traditional saccadic parameters and can potentially provide complementary information. SONDA shows larger effect sizes than VOG, suggesting that it provides robust and clinically relevant outcomes with a more intuitive task and shorter testing time.

Real-time diagnostic accuracy of blue light imaging, linked color imaging and white-light endoscopy for colorectal polyp characterization.

Background and study aims Fujifilm has developed a novel ELUXEO 7000 endoscope system that employs light-emitting diodes (LEDs) at four different wavelengths as light sources that enable blue light imaging (BLI), linked color imaging (LCI), and high-definition white-light endoscopy (HD-WLE). The aim of this study was to address the diagnostic accuracy of real-time polyp characterization using BLI, LCI and HD-WLE (ELUXEO 7000 endoscopy system). Patients methods This is a prespecified post-hoc analysis of a prospective study in which 22 experienced endoscopists (> 2,000 colonoscopies) from eight international centers participated. Using a combination of BLI, LCI, and HD-WLE, lesions were endoscopically characterized including a high- or low-confidence statement. Per protocol, digital images were created from all three imaging modalities. Histopathology was the reference standard. Endoscopists were familiar with polyp characterization, but did not take dedicated training for purposes of this study. Results Overall, 341 lesions were detected in 332 patients. Of the lesions, 269 histologically confirmed polyps with an optical diagnosis were included for analysis (165 adenomas, 27 sessile serrated lesions, and 77 hyperplastic polyps). Overall, polyp characterization was performed with high confidence in 82.9 %. The overall accuracy for polyp characterization was 75.1 % (95 % confidence interval [CI] 69.5-80.1 %), compared with an accuracy of 78.0 % (95 % CI 72.0-83.2 %) for high confidence assignments. The accuracy for endoscopic characterization for diminutive polyps was 74.7 % (95 %CI 68.4-80.3 %), compared with an accuracy of 78.2 % (95 % CI 71.4-84.0 %) for high-confidence assignments. Conclusions The diagnostic accuracy of BLI, LCI, and HD-WLE by experienced endoscopist for real-time polyp characterization seems limited (NCT03344289).

Case Report: "Niemann-Pick Disease Type C in a Catatonic Patient Treated With Electroconvulsive Therapy".

We describe a case of an adolescent male with Niemann-Pick Type C (NP-C), a neurodegenerative lysosomal lipid storage disorder, who presented with recurrent catatonia which required repeated treatment with electroconvulsive therapy (ECT). During the ECT-course, seizure threshold increased substantially, leading to questions about the influence of NP-C on neuronal excitability. In this exemplary ECT-patient, NP-C was diagnosed not until after the first ECT-course when initial psychopharmacology for catatonia had failed and antipsychotics and benzodiazepines showed significant side-effects. Clinicians should be aware of NP-C in patients referred for ECT, especially in the case of treatment resistance, neurological symptoms and intolerance of psychopharmacological drugs. As was shown in our NP-C patient, ECT can be repeatedly effective for catatonic features. In the literature, effectiveness of ECT in patients with NP-C has sparsely been reported. This case demonstrates that detection of NP-C is beneficial for patients because more optimal treatment with ECT can be provided earlier without further exposure to side-effects.

Safe, selective histopathological examination of gallbladder specimens: a systematic review.

BACKGROUND: Routine histopathological examination after cholecystectomy is costly, but the prevalence of unsuspected gallbladder cancer (incidental GBC) is low. This study determined whether selective histopathological examination is safe. METHODS: A comprehensive search of PubMed, Embase, Web of Science and the Cochrane Library was performed. Pooled incidences of incidental and truly incidental GBC (GBC detected during histopathological examination without preoperative or intraoperative suspicion) were estimated using a random-effects model. The clinical consequences of truly incidental GBC were assessed. RESULTS: Seventy-three studies (232 155 patients) were included. In low-incidence countries, the pooled incidence was 0·32 (95 per cent c.i. 0·25 to 0·42) per cent for incidental GBC and 0·18 (0·10 to 0·35) per cent for truly incidental GBC. Subgroup analysis of studies in which surgeons systematically examined the gallbladder revealed a pooled incidence of 0·04 (0·01 to 0·14) per cent. In high-incidence countries, corresponding pooled incidences were 0·83 (0·58 to 1·18), 0·44 (0·21 to 0·91) and 0·08 (0·02 to 0·39) per cent respectively. Clinical consequences were reported for 176 (39·3 per cent) of 448 patients with truly incidental GBC. Thirty-three patients (18·8 per cent) underwent secondary surgery. Subgroup analysis showed that at least half of GBC not detected during the surgeon's systematic examination of the gallbladder was early stage (T1a status or below) and of no clinical consequence. CONCLUSION: Selective histopathological examination of the gallbladder after initial macroscopic assessment by the surgeon seems safe and could reduce costs.

ANTECEDENTES: El examen histopatológico rutinario después de la colecistectomía es caro y la prevalencia de cáncer de vesícula biliar (gallbladder cancer, GBC) no sospechado o incidental es baja. Este estudio determinó si el examen histológico selectivo es seguro. MÉTODOS: Se realizó una búsqueda exhaustiva en PubMed, Embase, Web of Science y en la Biblioteca Cochrane. Se estimaron las incidencias agrupadas de GBC incidental y realmente incidental (GBC detectado durante el examen histopatológico sin sospecha previa o intraoperatoria) utilizando un modelo de efectos aleatorios. Además, se evaluaron las consecuencias clínicas del GBC realmente incidental. RESULTADOS: Se incluyeron 73 estudios (n = 232.155). En los países de baja incidencia, la incidencia agrupada fue de 0,32% para el GBC incidental (i.c. del 95% 0,25 a 0,42) y de 0,18% (0,10 a 0,35) para GBC realmente incidental. El análisis de subgrupos que incluye estudios en los que los cirujanos examinaron sistemáticamente la vesícula biliar reveló una incidencia agrupada de 0,04% (0,01 a 0,14). En los países de alta incidencia, las incidencias agrupadas correspondientes fueron 0,83% (0,58 a 1,18), 0,44% (0.2 a 0.91) y 0,08% (0,02 a 0,39), respectivamente. Se describieron consecuencias clínicas en 176 (39,3%) de 448 pacientes con GBC realmente incidental. Treinta y tres pacientes (18,6%) se sometieron a cirugía secundaria. El análisis por subgrupos mostró que al menos la mitad de los GBC no detectados durante el examen sistemático de la vesícula biliar por parte del cirujano eran tumores de estadio precoz (≤ T1a) y sin consecuencias clínicas. CONCLUSIÓN: El examen histológico selectivo de vesículas biliares después de la evaluación macroscópica inicial realizada por el cirujano parece seguro y podría reducir los costes.

Appendectomy for Therapy-Refractory Ulcerative Colitis Results in Pathological Improvement of Colonic Inflammation: Short-Term Results of the PASSION Study.

BACKGROUND AND AIMS: The objective of this study was to examine the modulating effect of an appendectomy on the disease course of therapy-refractory ulcerative colitis [UC] patients, and to analyse appendiceal pathological characteristics predictive of pathological response. METHODS: Patients with therapy-refractory UC, and referred for proctocolectomy, were invited to undergo laparoscopic appendectomy first. The primary end points were clinical response after 3 and 12 months. Secondary end points were endoscopic remission, failure, and pathologic response. Appendiceal specimens, and pre- and post-operative biopsies were histologically graded according to the validated Geboes score. RESULTS: Thirty patients [53% male] with a median age of 40 (interquartile range [IQR], 33-47) underwent appendectomy, with a median preoperative total Mayo score of 9 [IQR, 8-11]. After 12 months, 9 patients [30%] had lasting clinical response, of whom 5 [17%] were in endoscopic remission. Pathological evaluation was possible in 28 patients. After a median of 13.0 weeks [range 7-51], pathological response was seen in 13 patients [46%], with a median decrease of 2 points [range 1-3]. Appendiceal inflammation was highly predictive of pathological response when compared with no inflammation or extensive ulcerations [85% vs 20%, p = 0.001]. CONCLUSIONS: Appendectomy was effective in one-third of therapy-refractory UC patients, with a substantial proportion of patients demonstrating complete endoscopic remission after 1 year. Pathological response was seen in almost 50% of patients and was related to active inflammation in the appendix, limited disease, and shorter disease duration. These early results suggest that there is a UC patient group that may benefit from appendectomy.

Ataxia, dystonia and myoclonus in adult patients with Niemann-Pick type C.

BACKGROUND: Niemann-Pick type C (NP-C) is a rare autosomal recessive progressive neurodegenerative disorder caused by mutations in the NP-C 1 or 2 gene. Besides visceral symptoms, presentation in adolescent and adult onset variants is often with neurological symptoms. The most frequently reported presenting symptoms of NP-C in adulthood are psychiatric symptoms (38 %), cognitive decline (23 %) and ataxia (20 %). Myoclonus can be present, but its value in early diagnosis and the evolving clinical phenotype in NP-C is unclear. In this paper we present eight Dutch cases of NP-C of whom five with myoclonus. METHODS: Eight patients with genetically confirmed NP-C were recruited from two Dutch University Medical Centers. A structured interview and neuropsychological tests (for working and verbal memory, attention and emotion recognition) were performed. Movement disorders were assessed using a standardized video protocol. Quality of life was evaluated by questionnaires (Rand-36, SIP-68, HAQ). In four of the five patients with myoclonic jerks simultaneous EEG with EMG was performed. RESULTS: A movement disorder was the initial neurological symptom in six patients: three with myoclonus and three with ataxia. Two others presented with psychosis. Four experienced cognitive deficits early in the course of the disease. Patients showed cognitive deficits in all investigated domains. Five patients showed myoclonic jerks, including negative myoclonus. In all registered patients EEG-EMG coherence analysis and/or back-averaging proved a cortical origin of myoclonus. Patients with more severe movement disorders experienced significantly more physical disabilities. CONCLUSIONS: Presenting neurological symptoms of NP-C include movement disorders, psychosis and cognitive deficits. At current neurological examination movement disorders were seen in all patients. The incidence of myoclonus in our cohort was considerably higher (63 %) than in previous publications and it was the presenting symptom in 38 %. A cortical origin of myoclonus was demonstrated. Our data suggest that myoclonus may be overlooked in patients with NP-C. All patients scored significantly lower on physical domains of HRQoL. Symptomatic treatment of movement disorders may improve physical functioning and subsequently HRQoL.