Needle electromyography does not meaningfully impact findings in MR-neurography/-myography.

INTRODUCTION: Magnetic resonance neurography (MRN) and myography (MRM) are emerging imaging methods for detecting diseases of the peripheral nerve system (PNS). Most patients with PNS diseases also undergo needle electromyography (EMG). This study examined whether EMG led to lesions that were detectable using MRN/MRM and whether these lesions could impair image interpretation. METHODS: Ten patients who underwent clinically indicated EMG were recruited. MRN/MRM was performed before and 2-6 h after EMG, and if achievable, 2-3 days later. T2 signal intensity (SI) of the tibialis anterior muscle (TA) was quantified, and sizes and SI of the new lesions were measured. Visual rating was performed independently by three neuroradiologists. RESULTS: T2 lesions at the site of needle insertion, defined as focal edema, were detectable in 9/10 patients. The mean edema size was 31.72 mm2 (SD = 14.42 mm2 ) at the first follow-up. Susceptibility-weighted imaging lesions, defined as (micro) hematomas were detected in 5/10 patients (mean size, 23.85 mm2 [SD = 12.59 mm2 ]). General muscle SI of the TA did not differ between pre- and post-EMG examinations. Lesions size was relatively small, and the readers described image interpretation as not impaired by these lesions. DISCUSSION: This study showed that focal edema and hematomas frequently occurred after needle EMG and could be observed using MRN/MRM. As general muscle SI was not affected and image interpretation was not impaired, we concluded that needle EMG did not interfere with MRN/MRM.

Proposal of a diagnostic algorithm for radiation-induced dropped head syndrome in long-term childhood cancer survivors based on a prospective study in a specialized clinical setting and a review of the literature.

PURPOSE: To prospectively assess the incidence of Dropped Head Syndrome (DHS) in childhood cancer survivors (CCS) and to develop and evaluate a diagnostic algorithm for DHS. METHODS: A systematic literature search for DHS in combination with neck radiotherapy (RT) exposure was performed. Analyses and a combination of the most common examination methods were integrated into a diagnostic algorithm. Almost all CCSs visiting the local late effects clinic between May 2020 and April 2022 were included in the study. CCS exposed to neck RT with doses ≥ 19 Gy received standardized clinical and neurological assessment and, in case of abnormal results, an MRI scan to confirm muscle atrophy. RESULTS: Two hundred and five CCS were included of whom 41 received RT to the neck with ≥ 19 Gy. In the entire cohort and in the subgroup receiving RT, 2.4% and 12% of CCS were affected by DHS, respectively. Results of clinical and neurological assessment correlated well with MRI results. Neck circumference and neck/thigh ratio were lower after neck RT. Over 50% of CCS experienced neck disability and pain. CONCLUSIONS: A relevant proportion of CCS exposed to neck RT is affected by DHS. High concordance of MRI results with the neurological examination supports the clinical value of the diagnostic algorithm. Measurement of neck circumference might be an easy tool for assessment of neck muscle atrophy in survivors at risk. IMPLICATIONS FOR CANCER SURVIVORS: Integration of a diagnostic algorithm for DHS in standard long-term follow-up care facilitates diagnosis as well as initiation of early treatment and obviates the need for invasive examinations.

Identification of Patients With Glioblastoma Who May Benefit from Hypofractionated Radiotherapy.

BACKGROUND/AIM: Standard radiotherapy (RT) for glioblastoma lasts 6 weeks. We aimed to identify patients who would benefit from a hypofractionated approach. PATIENTS AND METHODS: In 167 patients receiving standard fractionation, 10 factors were analyzed for local control (LC) and overall survival (OS). A survival score was developed and compared to a previous instrument. RESULTS: On multivariate analysis, better LC was significantly associated with the presence of only one lesion and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Better OS was associated with one lesion, better performance status, MGMT promoter methylation, and receipt of chemotherapy. Lesion diameter ≤40 mm and upfront resection were associated with improved OS on univariate analyses. Based on assigning scores to these six factors, three groups, with 32-35, 36-44 and 45-48 points, were designed with 12-month OS-rates of 0%, 56%, and 92%, respectively. Accuracy in predicting death within 12 months and survival ≥12 months was 100% and 92%, respectively, versus 67% and 83% with the previous scoring system. CONCLUSION: A new survival score with higher accuracy was developed for patients with glioblastoma. Our model can be utilized to individualize RT dose-fractionation recommendations for glioblastoma.

Pre-treatment Emotional Distress in Patients Irradiated for Malignant Glioma.

BACKGROUND/AIM: A recommendation of radiotherapy for patients with malignant gliomas may trigger emotional distress. Frequency and risk factors of this complication were investigated. PATIENTS AND METHODS: Prevalence of six emotional problems and 11 potential risk factors were evaluated in 103 patients irradiated for grade II-IV gliomas. p-Values <0.0045 were considered significant. RESULTS: Seventy-six patients (74%) had ≥1 emotional problem. Prevalence of specific emotional problems ranged between 23% and 63%. Associations were found between ≥5 physical problems and worry (p=0.0010), fear (p=0.0001), sadness (p=0.0023), depression (p=0.0006), and loss of interest (p=0.0006), and Karnofsky performance score ≤80 and depression (p=0.0002). Trends were found for physical problems and nervousness (p=0.040), age ≥60 years and depression (p=0.043) or loss of interest (p=0.045), grade IV glioma and sadness (p=0.042), and ≥2 involved sites and loss of interest (p=0.022). CONCLUSION: Three-fourths of glioma patients had pre-radiotherapy emotional distress. Psychological support should be offered very soon, particularly for high-risk patients.

Sensitivity and specificity in signal detection with the reporting odds ratio and the information component.

PURPOSE: As measures of association between an adverse drug reaction (ADR) and exposure to a drug the reporting odds ratio (ROR) and the information component (IC) can be used. We sought to test the reliability of signal detection with these. METHODS: We simulated ADR counts as binomially distributed random numbers for different expected ADR frequencies and theoretical reporting odds ratios (RORs). We then calculated the empirical IC and the empirical ROR and their confidence intervals. The rate of signals that was detected despite a theoretical ROR of 1 represented the false positive rate, and represented the sensitivity if the ROR was >1. RESULTS: For expected case counts below 1 the false positive rate oscillates from 0.01 to 0.1 even though 0.025 were intended. Even beyond expected case counts of 5 oscillations can cover a range of 0.018 to 0.035. The first n oscillations with the largest amplitude are eliminated if a minimum case count of n is required. To detect an ROR of 2 with a sensitivity of 0.8, a minimum of 12 expected ADRs are required. In contrast, 2 expected ADRs suffice to detect an ROR of 4. CONCLUSION: Summaries of measures for disproportionality should include the expected number of cases in the group of interest if a signal was detected. If no signal was detected the sensitivity for the detection of a representative ROR or the minimum ROR that could be detected with probability 0.8 should be reported.

Increasing Seizure Activity During Radiation Treatment for High-grade Gliomas - Final Results of a Prospective Interventional Study.

BACKGROUND/AIM: Little is known regarding seizures during radiotherapy for brain tumors. This prospective study investigated seizure activity in patients irradiated for high-grade gliomas. PATIENTS AND METHODS: Using a seizure diary, progression of seizure activity was evaluated in 22 patients receiving chemoradiation for grade III (n=1) or IV (n=21) gliomas. Progression was defined as increased frequency of any and/or generalized seizures (>50%) or increased anti-epileptic medication (≥25%). Patients' satisfaction with the diary was assessed using a questionnaire (six scales of 1-7 points). Uni- and multivariable analyses were performed including baseline seizure activity, age, sex, resection, tumor site, performance score, and history of epilepsy/seizures. RESULTS: Ten patients (45%) experienced progression of seizure activity during their radiotherapy course, mainly due to increased seizure frequency (nine patients=41%). Mean values of patients' satisfaction scores ranged between 3.92 and 4.92 points. CONCLUSION: Radiotherapy of high-grade gliomas can increase seizure activity. Patients require close monitoring to initiate or adjust anti-epileptic medication.

A Simple Gain-Based Evaluation of the Video Head Impulse Test Reliably Detects Normal Vestibulo-Ocular Reflex Indicative of Stroke in Patients With Acute Vestibular Syndrome.

Objective: The head impulse test (HIT) assesses the vestibulo-ocular reflex (VOR) and is used to differentiate vestibular neuritis (abnormal VOR) from stroke (normal VOR) in patients presenting with an acute vestibular syndrome (AVS). The video-oculography-based HIT (vHIT) quantifies VOR function and provides information imperceptible for the clinician during clinical bedside HIT. However, the vHIT-like an electrocardiogram-requires experienced interpretation, which is especially difficult in the emergency setting. This calls for a simple, reliable and rater-independent way of analysis. Methods: We retrospectively collected 171 vHITs performed in patients presenting with AVS to our emergency department. Three neuro-otological experts comprehensively assessed the vHITs including interpretability (artifacts), VOR gain (eye/head velocity ratio), velocity profile (abrupt decline) and corrective saccades (overt/covert). Their consensus rating (abnormal/peripheral vs. normal/central) was compared to a simple algorithm that automatically classified the vHITs based on a single VOR gain cutoff (0.7). Results: Inter-rater agreement between experts was high (Fleiss' kappa = 0.74). Five (2.9 %) vHITs were "uninterpretable" according to experts' consensus, 80 (46.8 %) were rated "normal" and 86 (50.3 %) "abnormal". The algorithm had substantial agreement with the experts' consensus (Cohen's kappa = 0.75). Importantly, it correctly classified all of the normal/central vHITs denoted by the experts (100% specificity) and at the same time it had sufficient sensitivity (75.6%) in detecting abnormal/peripheral vHITs. Conclusion: A simple, automated, gain-based evaluation of the vHIT reliably detects normal/central VOR and may be a feasible and effective tool to screen AVS patients for potentially underlying stroke in the emergency setting.

The risk of worsening of myasthenia by cardiovascular medication as reflected by reporting frequency.

BACKGROUND AND PURPOSE: Some groups of cardiovascular drugs (beta-blocking drugs, Ca antagonists, antiarrhythmics) are listed as potentially worsening myasthenia. An empirical basis for alternative recommendations for antihypertensive and antiarrhythmic therapy in myasthenia patients has not yet been provided. METHODS: From the World Health Organization pharmacovigilance database, we retrieved total and myasthenia-related counts of adverse drug reactions for various groups of drugs used in cardiovascular disease and drugs with related mechanism of action used in other indications. We calculated the reporting odds ratio as a measure of a disproportional fraction of myasthenia-related events among all events. A 95% confidence interval of reporting odds ratio (ROR) >1 was taken as an indication for a higher risk. Because our approach involves a considerable number of tests, this situation is referred to as a signal that requires additional confirmation. RESULTS: A signal for an increased risk was noted for tizanidine, for alpha-blocking drugs, for beta-blocking drugs, and for Ca antagonists. ROR indicated a lower-than-average risk for salbutamol, angiotensin receptor antagonists, oral anticoagulants, thrombocytic function inhibitors, and heparins. CONCLUSIONS: Angiotensin receptor antagonists, angiotensin-converting enzyme inhibitors, and diuretics seem to be safe in antihypertensive therapy. Surprisingly, and yet requiring confirmation by case reports, alpha receptor-blocking drugs seem to carry a risk of myasthenia worsening. Amiodarone seems to be a safe alternative in antiarrhythmic therapy in patients with myasthenia.

A prospective interventional study evaluating seizure activity during a radiotherapy course for high-grade gliomas (SURF-ROGG).

BACKGROUND: Gliomas are often associated with symptoms including seizures. Most patients with high-grade gliomas are treated with radiotherapy or radio-chemotherapy. Since irradiation causes inflammation, it may initially aggravate symptoms. Studies focusing on seizure activity during radiotherapy for gliomas are not available. Such knowledge may improve patient monitoring and anti-epileptic treatment. This study evaluates seizure activity during radiotherapy for high-grade gliomas. METHODS: The primary objective this prospective interventional study is the evaluation of seizure activity during a course of radiotherapy for high-grade gliomas. Progression of seizure activity is defined as increased frequency of seizures by > 50%, increased severity of seizures, or initiation/increase by ≥25% of anti-epileptic medication. Seizure frequency up to 6 weeks following radiotherapy and electroencephalography activity typical for epilepsy will also be evaluated. Patients keep a seizure diary during and up to 6 weeks following radiotherapy. Every day, they will document number (and type) of seizures and anti-epileptic medication. Once a week, the findings of the diary are checked and discussed with a neurologist to initiate or adjust anti-epileptic medication, if necessary. Patients complete a questionnaire regarding their satisfaction with the seizure diary. If the dissatisfaction rate is > 40%, the seizure diary will be considered not suitable for the investigated indication. Thirty-five patients (32 patients plus drop-outs) should be enrolled. With this sample size, a one-sample binomial test with a one-sided significance level of 2.5% has a power of 80% to yield statistical significance, if the rate of patients with progression of seizure activity is 30% (rate under the alternative hypothesis), assuming a 'natural' background progression-rate of 10% without radiotherapy (null hypothesis). DISCUSSION: If an increase in seizure activity during a course of radiotherapy for high-grade glioma occurs, the findings of this study may pave the way for a larger prospective trial and will likely lead to closer patient monitoring and better anti-epileptic treatment. TRIAL REGISTRATION: clinicaltrials.gov ( NCT04552756 ); registered on 16th of September, 2020.

Worsening of myasthenia due to antiepileptic, antipsychotic, antidepressant, and sedative medication: An estimation of risk based on reporting frequency.

BACKGROUND AND PURPOSE: Many drugs can worsen myasthenia symptoms. The clinician usually relies on cautionary lists compiled according to case reports. We intended to provide a quantitative basis for a risk comparison within the groups of antiepileptic, antidepressant, neuroleptic, and sedative drugs. METHODS: We extracted adverse drug reaction (ADR) counts (total and myasthenia related) for drugs from these groups and calculated the reporting odds ratio (ROR) within the drug groups from the World Health Organization pharmacovigilance database. For a given drug, the ROR was increased above 1 if the proportion of myasthenia-related ADRs for this drug was larger than the same proportion for the rest of drugs in that same group. If the 95% confidence interval of ROR was >1, this was taken as a signal for a higher risk of the given drug as compared to the average of the respective group. RESULTS: Gabapentin, sertraline, citalopram, lithium, and amisulpride had a signal for the ROR to be increased above 1 within their respective groups. Bupropion, desvenlafaxine, duloxetine, escitalopram, and paroxetine had ROR values <1. For all other drugs, 1 was within the ROR confidence interval. CONCLUSIONS: For gabapentin and lithium, the analysis of RORs confirmed case reports and cautionary lists. For a number of antidepressant drugs associated with a higher-than-average risk, no case reports exist substantiating our results. For these drugs, special attention should be paid to this risk. The remarkable difference between citalopram and escitalopram could prompt experimental work to confirm differential influence of the two preparations on neuromuscular transmission.

A New Survival Score for Patients Receiving Radiotherapy for Newly Diagnosed Glioblastoma Multiforme.

BACKGROUND/AIM: In a previous study investigating radiotherapy for newly diagnosed glioblastoma multiforme (GBM), significant or almost significant associations with survival were found for performance status, upfront resection, O6-methylguanine-DNA methyl-transferase (MGMT) promoter methylation and unifocal GBM. This study aimed to create a survival score based on these factors. PATIENTS AND METHODS: Most of the 81 patients included received resection of GBM followed by radiochemotherapy (59.4 Gy/33 or 60 Gy/30 fractions). The previously identified predictors of survival were re-evaluated. Factors significantly associated with survival were used for the score. RESULTS: All factors were significantly associated with survival. For each factor, 0 points (less favorable survival) or 1 point (more favorable survival) were assigned and added for each patient. Three groups were designed, 0-1 (n=10), 2 (n=21) and 3-4 points (n=50); 12-month survival rates were 0%, 38% and 78% (p<0.001). CONCLUSION: A new survival score was created for patients requiring radiotherapy for GBM that can improve treatment personalization.

What guides decision-making on intravenous thrombolysis in acute vestibular syndrome and suspected ischemic stroke in the posterior circulation?

Intravenous thrombolysis (IVT) is rarely performed in dizzy patients with acute vestibular syndrome (AVS) or acute imbalance (AIS) even if posterior circulation stroke (PCS) is suspected. Decision-making may be affected by uncertainties in discriminating central from peripheral vestibulopathy or concerns of IVT-related harm, particularly intracerebral hemorrhage (ICH), but related studies are missing. Using an in-house register of dizzy patients coming to the emergency room, we identified 29 AVS/AIS patients who presented within 4.5 h after onset, revealed clinical signs indicative of PCS (central oculomotor signs, mild focal abnormalities), and had non-contrast computed tomography (NCCT). Patients treated with IVT (n = 15) were compared to NoIVT patients (n = 14) with regard to clinical and imaging (including perfusion computed tomography, CTP) parameters, occurrence of ICH and short-term clinical outcome (NIHSS improvement; ability to walk independently). IVT and NoIVT patients did not differ in baseline characteristics, central oculomotor signs, or clinical outcome. IVT patients more often exhibited disabling vestibular symptoms (severe dizziness/vertigo, inability to stand unsupported) and focal abnormalities than NoIVT patients. There was no ICH in either group. CTP was performed in 0% of NoIVT versus 80% of IVT patients, seven of twelve revealing posterior circulation hypoperfusion. Comparison of initial hypoperfusion (CTP) and final stroke (NCCT) revealed IVT-related benefit (smaller lesion) in three of seven IVT patients. In AVS/AIS patients with suspected PCS, disabling vestibular symptoms, focal neurological deficits, and hypoperfusion on CTP seem to direct decision-making pro IVT. In our small cohort, there were no significant IVT-related clinical benefits, no IVT-related ICHs, and salvage of brain tissue in some patients.

Usability of the head impulse test in routine clinical practice in the emergency department to differentiate vestibular neuritis from stroke.

BACKGROUND AND PURPOSE: The bedside head impulse test (bHIT) is used to differentiate vestibular neuritis (VN) from posterior circulation stroke (PCS) in patients presenting with acute vestibular syndrome (AVS). If assessed by neuro-otological experts, diagnostic accuracy is high. We report on its diagnostic accuracy when applied by nonexperts during routine clinical practice in the emergency department (ED), its impact on patient management, and the potential diagnostic yield of the video-oculography-supported head impulse test (vHIT). METHODS: Medical chart review of 38 AVS patients presenting to our university medical center's ED, assessed by neurology residents. We collected bHIT results (abnormal/peripheral or normal/central) and whether patients were admitted to the stroke unit or general neurological ward. Final diagnosis (VN, n = 24; PCS, n = 14) was determined by clinical course, magnetic resonance imaging, and vHIT. RESULTS: The bHIT's accuracy was only 58%. Its sensitivity for VN was high (88%), but due to many false-abnormal bHITs in PCS (36%), the specificity was low (64%). The vHIT yielded excellent specificity (100%) and moderate sensitivity (67%). The decision on the patient's further care was almost arbitrary and independent from the bHIT: 58% of VN and 57% of PCS patients were admitted to the stroke unit. CONCLUSIONS: The bHIT, applied by nonexperts during routine practice in the ED, has low accuracy, is too often mistaken as abnormal/peripheral, and is not consistently used for patients' in-hospital triage. As false-abnormal bHITs can lead to misdiagnosis/mistreatment of stroke patients, we recommend that bHIT applied by nonexperts should be reassessed by a neuro-otological expert or preferably quantitative vHIT in the ED.

Risk of acute brain lesions in dizzy patients presenting to the emergency room: who needs imaging and who does not?

The usefulness of brain imaging studies in dizzy patients presenting to the emergency department (ED) is controversial. We aimed to assess the 'real-world' probability of ischemic stroke and other acute brain lesions (ABLs) in these patients to create an algorithm that helps decision-making on whether which and when brain imaging is needed. By reviewing medical records, we identified 610 patients presenting with dizziness, vertigo or imbalance to our university hospital's ED and receiving neurological workup. We collected timing/triggers of symptoms, ABCD2 score, focal neurological abnormalities, HINTS (head impulse, nystagmus, test-of-skew) and other central oculomotor signs. ABLs were extracted from CT/MRI reports. Uni-/multivariate logistic regression analyses investigated associations between clinical parameters and ABLs. Finally, the likelihood of ABLs was assessed for different clinically defined subgroups ('dizziness syndromes'). Early CT (day 1) was performed in 539 (88%) and delayed MR imaging (median: day 4) in 299 (49%) patients. ABLs (89% ischemic stroke) were revealed in 75 (24%) of 318 patients with adequate imaging (MRI or lesion-positive CT). The risk for ABLs increased with the presence of central oculomotor signs (odds ratio 2.8, 95% confidence interval 1.5-5.2) or focal abnormalities (OR 3.3, 95% CI 1.8-6.2). The likelihood of ABLs differed between dizziness syndromes, e.g., HINTS-negative acute vestibular syndrome: 0%, acute imbalance syndrome with ABCD2-score ≥ 4: 50%. We propose a clinical pathway, according to which patients with HINTS-negative acute vestibular syndrome should not receive brain imaging, whereas imaging is suggested in dizzy patients with acute imbalance, central oculomotor signs or focal abnormalities.

Regeneration of Denervated Skeletal Muscles - Brunelli's CNS-PNS Paradigm.

The restoration of voluntary muscle activity in posttraumatic paraplegia in both animal experiments and other clinical applications requires reproducibility of a technically-demanding microsurgical procedure, limited by physicians' understanding of Brunelli's spinal cord grafting paradigm. The insufficient clinical investigation of the long-term benefits of the CNS-PNS graft application warrants additional inquiry. The objective of this study is to explore the potential benefits of the first replicated, graft-induced neuroregeneration of denervated skeletal muscle regarding long-term clinical outcomes and to investigate the effect of Cerebrolysin on neuromodulation. A randomized study evaluating 30 rats, approved by the National Animal Ethics Advisory Committee was performed. The medication was administered postoperatively. For 14 days, 12 rats received Cerebrolysin (serum), 11 received NaCl 0.9% (shams), and 7 were controls. For microsurgery, the lateral corticospinal tract T10 was grafted to the denervated internal obliquus abdominal muscle. On day 90, intraoperative proof of reinnervation was observed. On day 100, 15 rats were euthanized for fixation, organ removal, and extensive histology-morphology examination, and the Wei-Lachin statistical procedure was employed. After an open revision of 16 rats, 8 were CMAP positive. After intravenous Vecuronium application, two (Cerebrolysin, NaCl) out of two rats showed an incomplete compound muscle action potential (CMAP) loss due to glutamatergic and cholinergic co-transmission, while two others showed a complete loss of amplitude. Cerebrolysin medication initiated larger restored muscle fiber diameters and less scarring. FB+ neurons were not observed in the brain but were observed in the Rexed laminae. Brunelli's concept was successfully replicated, demonstrating the first graft induced existence of cholinergic and glutamatergic neurotransmission in denervated grafted muscles. Statistics of the histometric count of muscle fibers revealed larger fiber diameters after Cerebrolysin. Brunelli's CNS-PNS experimental concept is suitable to analyze graft-neuroplasticity focused on the voluntary restoration of denervated skeletal muscles in spinal cord injury. Neuroprotection by Cerebrolysin is demonstrated.

Role of the Patient's History of Vestibular Symptoms in the Clinical Evaluation of the Bedside Head-Impulse Test.

OBJECTIVE: Our aim was to identify the role of the investigators' knowledge of the patient's history of vestibular symptoms (PVH) in the clinical evaluation of the bedside head-impulse test (bHIT). We hypothesized that this knowledge will reduce uncertainty and improve bHIT accuracy when compared to quantitative analysis of the vestibulo-ocular reflex by video head-impulse test (vHIT). METHODS: We looked for changes in the clinical assessment of the bHIT in 594 consecutive patients before and after taking PVH. bHIT was performed by 12 clinical neurologists with various clinical experience in neuro-otological diseases (novices to long-standing experts). vHIT was analyzed by four experts being blinded for the patients' clinical presentation and history of symptoms. The confidence of bHIT and vHIT was rated (0-100%). RESULTS: One hundred fifty-four (15%) of 1,030 bHIT of all eligible patients (n = 515) were rated pathological. Thirty-five (22.7%) of them were rated bilateral vestibulopathies. Sensitivity of bHIT reached 56.3%, its specificity 92.4%; the positive predictive value (PPV) was 41.5% and the negative predictive value 95.7%. These data did not differ between bHIT before and after PVH. bHIT after PVH (post-bHIT) differed from pre-bHIT in 44.3%, usually with regard to the level of confidence but also in polarity (5%). The accuracy of changes in bHIT depended on the direction of change: a "normal" post-bHIT was correct in 92.3% while only 39.8% of pathological post-bHIT were pathological on vHIT. However, sensitivity of a pathological post-bHIT depended on the clinical experience in taking PVH and bHIT: the PPV was 20.5% in novices as compared to 69.6% in experts. CONCLUSION: The study shows that PVH changes the certainty and/or polarity of the clinical evaluation of bHIT. Unlike expected, the increase in confidence in post-bHIT is associated with a consistently high specificity but no increase in sensitivity. Accuracy of changes in post-bHIT depends on the investigators' clinical experience: it increases only in experts but not novices. Since novices show only a poor PPV and moderate sensitivity of bHIT, pathological bHITs should be controlled by vHIT, even in patients with a positive PVH. By contrast, confirmed normal post-bHIT is usually correct.

Visual and non-visual motion information processing during pursuit eye tracking in schizophrenia and bipolar disorder.

Despite many reports on visual processing deficits in psychotic disorders, studies are needed on the integration of visual and non-visual components of eye movement control to improve the understanding of sensorimotor information processing in these disorders. Non-visual inputs to eye movement control include prediction of future target velocity from extrapolation of past visual target movement and anticipation of future target movements. It is unclear whether non-visual input is impaired in patients with schizophrenia. We recorded smooth pursuit eye movements in 21 patients with schizophrenia spectrum disorder, 22 patients with bipolar disorder, and 24 controls. In a foveo-fugal ramp task, the target was either continuously visible or was blanked during movement. We determined peak gain (measuring overall performance), initial eye acceleration (measuring visually driven pursuit), deceleration after target extinction (measuring prediction), eye velocity drifts before onset of target visibility (measuring anticipation), and residual gain during blanking intervals (measuring anticipation and prediction). In both patient groups, initial eye acceleration was decreased and the ability to adjust eye acceleration to increasing target acceleration was impaired. In contrast, neither deceleration nor eye drift velocity was reduced in patients, implying unimpaired non-visual contributions to pursuit drive. Disturbances of eye movement control in psychotic disorders appear to be a consequence of deficits in sensorimotor transformation rather than a pure failure in adding cognitive contributions to pursuit drive in higher-order cortical circuits. More generally, this deficit might reflect a fundamental imbalance between processing external input and acting according to internal preferences.

Multicentre comparison of a diagnostic assay: aquaporin-4 antibodies in neuromyelitis optica.

OBJECTIVE: Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD). METHODS: Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1). RESULTS: Results of tests on 92 controls identified 12assays as highly specific (0-1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5-100%) of all 21 assays. The specificities (85.8-100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples. CONCLUSIONS: The cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology.