Structural and functional spatial dynamics of microbial communities in aerated and non-aerated horizontal flow treatment wetlands.

A multiphasic study using structural and functional analyses was employed to investigate the spatial dynamics of the microbial community within five horizontal subsurface flow treatment wetlands (TWs) of differing designs in Germany. The TWs differed in terms of the depth of media saturation, presence of plants (Phragmites australis), and aeration. In addition to influent and effluent water samples, internal samples were taken at different locations (12.5 %, 25 %, 50 %, and 75 % of the fractional distance along the flow path) within each system. 16S rRNA sequencing was used for the investigation of microbial community structure and was compared to microbial community function and enumeration data. The microbial community structure in the unaerated systems was similar, but different from the aerated TW profiles. Spatial positioning along the flow path explained the majority of microbial community dynamics/differences within this study. This was mainly attributed to the availability of nutrients closer to the inlet which also regulated the fixed biofilm/biomass densities. As the amount of fixed biofilm decreased from the inlet to the TW outlets, structural diversity increased, suggesting different microbial communities were present to handle the more easily utilized/degraded pollutants near the inlet vs. the more difficult to degrade and recalcitrant pollutants closer to the outlets. This study also confirmed that effluent water samples do not accurately describe the microbial communities responsible for water treatment inside a TW, highlighting the importance of using internal samples for investigating microbial communities in TWs. The results of this study reinforce an existing knowledge gap regarding the potential for TW design modifications which incorporate microbial community spatial dynamics (heterogeneity). It is suggested that utilizing step-feeding could allow for improved water treatment within the same areal footprint, and modifications enhancing co-metabolic processes could assist in improving the treatment of more difficult to degrade or recalcitrant compounds such as micropollutants.

Pattern analysis of peripheral-vestibular deficits with machine learning using hierarchical clustering.

Background Disorders affecting the vestibular organs (semicircular canals, utriculus, sacculus), may result in distinct patterns of peripheral-vestibular loss that may facilitate the diagnostic assessment. When neuropathological tests of these sensors are available, it is possible to classify responses as being due to different deficit types. Objective To provide a topical review and to summarize recent advances in pattern-recognition of unilateral and bilateral vestibular disease by use of hierarchical cluster analysis (HCA) as published by the authors. Hypothesis We propose that certain patterns of peripheral-vestibular loss are associated with specific underlying disorders and that HCA is a suitable approach to identify such patterns. Discussion In the studies reviewed, disease-specific patterns could be recognized in different patient cohorts, with anterior-canal sparing being a hallmark feature in aminoglycoside-related bilateral vestibulopathy, Menière's disease and vestibular Schwannoma. The reasons for such anterior-canal sparing remain subject to debate, but potential explanations include reduced toxic exposure, faster recovery and lower vulnerability of the anterior canals. The pattern observed in acute superior-branch vestibular neuropathy, i.e., involvement of the horizontal and anterior canal and the utricle, matches neural inner-ear physiology. The broadly varying extent of damage to the different vestibular sensors even within given disorders underlines the necessity for detailed vestibular-testing. Conclusion HCA significantly facilitates pattern-identification in unilateral and bilateral vestibulopathies and underlines the extensive range of vestibular end-organ damage in the different study populations and subgroups. The large number of existing clustering algorithms with distinct strengths and weaknesses emphasizes the need for careful selection of the most suitable algorithm.

Impact of autoimmune comorbidity on fatigue, sleepiness and mood in myasthenia gravis.

BACKGROUND: Disease burden in myasthenia gravis (MG) and in other autoimmune disorders is often determined by common accompanying symptoms such as fatigue, sleepiness and mood disturbances. Many MG patients have a second autoimmune disease, but it is unclear whether autoimmune comorbidities add to the severity of fatigue, sleepiness and mood disturbances. METHODS: We ascertained the presence of autoimmune comorbidities in 69 well-characterized MG patients. To assess fatigue, sleepiness and mood disturbances, we applied the Fatigue Severity Scale (FSS), the Fatigue Impact Scale (FIS), the Epworth Sleepiness Scale (ESS), as well as the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) to all patients. RESULTS: Thirteen MG patients had concomitant autoimmune thyroid disease (AITD), including 1 patient with rheumatoid arthritis as third autoimmune disease. Fatigue (68.1%), excessive daytime sleepiness (14.5%), moderate-severe depression (20.3%) and anxiety (26.1%) were common, but MG patients with and without autoimmune comorbidities had similar FSS, FIS, ESS, BDI and STAI scores. The presence of autoimmune comorbidities was not associated with altered clinical and immunological MG characteristics, but MG patients with autoimmune comorbidities have more often been treated with corticosteroids than patients without autoimmune comorbidities (92.3% vs. 60.7%; p = 0.03). CONCLUSIONS: While many MG patients were affected by fatigue, sleepiness, depression and anxiety, the present study does not suggest that coexisting autoimmune diseases substantially contribute to the magnitude of these cumbersome comorbid symptoms. However, the higher frequency of steroid treatment may have counterbalanced the effects of the autoimmune comorbidity.

Fatigue in patients with myasthenia gravis.

BACKGROUND: The subjective feeling of fatigue in myasthenia gravis (MG) is poorly elucidated, in part because it is often confounded with the objective sign of muscle fatigability. Another reason is the paucity of validated fatigue questionnaires in MG. METHODS: We applied the 9-item Fatigue Severity Scale (FSS) and the 40-item Fatigue Impact Scale (FIS) to 73 MG patients and 230 age- and sex-matched control subjects. We ascertained levels of education, marital status, and comorbidities such as depression, sleepiness, sleep times and sleep debt. Disease severity was graded according to the Myasthenia Gravis Foundation of America (MGFA) classification. RESULTS: All fatigue scores, with the exception of the cognitive FIS subscale, were higher in MG patients than controls. In MG, the prevalence of fatigue (defined by FSS scores ≥ 4.0) was 70%. Multiple regression analyses revealed several independent associates of fatigue, including depression (all fatigue scales), MGFA stage (FSS, physical FIS), female sex (cognitive and psychosocial FIS), and sleep debt (physical FIS). CONCLUSION: Fatigue in MG is highly prevalent, mainly physical, and influenced by depressive symptoms, disease severity, female sex and sleep debt. Cognitive fatigue in MG may not be a direct disease manifestation, but secondary to depression. The FSS and FIS represent reliable and validated tools, appropriate to discern meaningful clinical aspects of fatigue in MG. Clinical recognition of the complexity of fatigue may foster individualized treatment approaches for affected MG patients.

Compensatory saccades in head impulse testing influence the dynamic visual acuity of patients with unilateral peripheral vestibulopathy1.

BACKGROUND: Both the dynamic visual acuity (DVA) test and the video head-impulse test (vHIT) are fast and simple ways to assess peripheral vestibulopathy. After losing peripheral vestibular function, some patients show better DVA performance than others, suggesting good compensatory mechanisms. It seems possible that compensatory covert saccades could be responsible for improved DVA. OBJECTIVE: To investigate VOR gain and compensatory saccades with vHIT and compare them to the DVA of patients with unilateral peripheral vestibulopathy. METHODS: VOR gain deficit and compensatory saccades were measured with vHIT. VOR gain was calculated for each trial as mean eye velocity divided by mean head velocity during 4 samples between 24 ms - 40 ms after peak head acceleration. DVA was then assessed. VHIT was analyzed for percentage of covert saccades and for cumulative overt saccade amplitude. Twenty-four patients with unilateral vestibular deficit were included. A control group of 113 healthy subjects provided normal data. RESULTS: On the affected side, pathologic values for DVA (mean 0.83 logMAR±0.25 SD) and VOR gain (mean 0.16±0.13) were obtained, whereas the healthy side showed normal values (0.53 logMAR±0.15 for DVA and 0.89±0.18 for VOR gain). Yet, DVA performance on the affected side was significantly better in patients with higher covert saccade percentage (p = 0.012) and lower cumulative overt saccade amplitude (p < 0.001). CONCLUSION: Compensatory covert saccades seen in vHIT correlate with improved performance of DVA-testing in patients with unilateral peripheral vestibular loss. Hence, in addition to testing peripheral vestibulopathy, our results indicate a way for assessing rehabilitatory compensation in such patients by DVA in addition to vHIT.

Gaze holding deficits discriminate early from late onset cerebellar degeneration.

The vestibulo-cerebellum calibrates the output of the inherently leaky brainstem neural velocity-to-position integrator to provide stable gaze holding. In healthy humans small-amplitude centrifugal nystagmus is present at extreme gaze-angles, with a non-linear relationship between eye-drift velocity and eye eccentricity. In cerebellar degeneration this calibration is impaired, resulting in pathological gaze-evoked nystagmus (GEN). For cerebellar dysfunction, increased eye drift may be present at any gaze angle (reflecting pure scaling of eye drift found in controls) or restricted to far-lateral gaze (reflecting changes in shape of the non-linear relationship) and resulting eyed-drift patterns could be related to specific disorders. We recorded horizontal eye positions in 21 patients with cerebellar neurodegeneration (gaze-angle = ±40°) and clinically confirmed GEN. Eye-drift velocity, linearity and symmetry of drift were determined. MR-images were assessed for cerebellar atrophy. In our patients, the relation between eye-drift velocity and gaze eccentricity was non-linear, yielding (compared to controls) significant GEN at gaze-eccentricities ≥20°. Pure scaling was most frequently observed (n = 10/18), followed by pure shape-changing (n = 4/18) and a mixed pattern (n = 4/18). Pure shape-changing patients were significantly (p = 0.001) younger at disease-onset compared to pure scaling patients. Atrophy centered around the superior/dorsal vermis, flocculus/paraflocculus and dentate nucleus and did not correlate with the specific drift behaviors observed. Eye drift in cerebellar degeneration varies in magnitude; however, it retains its non-linear properties. With different drift patterns being linked to age at disease-onset, we propose that the gaze-holding pattern (scaling vs. shape-changing) may discriminate early- from late-onset cerebellar degeneration. Whether this allows a distinction among specific cerebellar disorders remains to be determined.

Inferior oblique muscle anteriorization in congenital superior oblique palsy.

BACKGROUND: Inferior oblique muscle overaction of variable amounts is usually present with congenital superior oblique palsy. Inferior oblique muscle anteriorization has been described as a suitable surgical procedure in this entity. The aim of this study was to investigate the effect of inferior oblique muscle anteriorization in patients with congenital superior oblique palsy on vertical, torsional and horizontal alignment. PATIENTS AND METHODS: The study was designed as an institutional retrospective cohort study. 45 patients with congenital superior oblique palsy (15 female, 30 male; mean age 36 years ± 19.2 SD, ranging from 6 to 75 years) underwent inferior oblique muscle anteriorization between 2000 and 2010. Preoperative amounts of vertical, torsional and horizontal deviation (using Harms tangent screen), measurements of Bielschowsky head tilt phenomenon as well as stereopsis (Lang test) were compared with findings three months and one year postoperatively. RESULTS: Preoperative vertical deviation in primary position measured 10.1° (mean; range 0-19). Three months postoperatively vertical deviation was significantly reduced (p<0.001) to 4° (mean; range 0-20). After one year vertical deviation measured 3.5° (mean; range 0-15). The values three months postoperatively did not significantly differ from those one year postoperatively (p=0.46). CONCLUSIONS: Inferior oblique muscle anteriorization leads to a significant and sustained improvement of ocular alignment in patients with congenital superior oblique palsy of various degrees of severity. Thus the procedure is recommendable as a first line treatment in this clinical situation.

Vestibular function after acute vestibular neuritis.

PURPOSE: To review the extent and mechanism of the recovery of vestibular function after sudden, isolated, spontaneous, unilateral loss of most or all peripheral vestibular function - usually called acute vestibular neuritis. METHODS: Critical review of published literature and personal experience. RESULTS: The symptoms and signs of acute vestibular neuritis are vertigo, vomiting, nystagmus with ipsiversive slow-phases, ipsiversive lateropulsion and ocular tilt reaction (the static symptoms) and impairment of vestibulo-ocular reflexes from the ipsilesional semicircular canals on impulsive testing (the dynamic symptoms). Peripheral vestibular function might not improve and while static symptoms invariably resolve, albeit often not totally, dynamic symptoms only improve slightly if at all. CONCLUSIONS: The persistent loss of balance that some patients experience after acute vestibular neuritis can be due to inadequate central compensation or to incomplete peripheral recovery and vestibular rehabilitation has a role in the treatment of both.

The video head impulse test: diagnostic accuracy in peripheral vestibulopathy.

BACKGROUND: The head impulse test (HIT) is a useful bedside test to identify peripheral vestibular deficits. However, such a deficit of the vestibulo-ocular reflex (VOR) may not be diagnosed because corrective saccades cannot always be detected by simple observation. The scleral search coil technique is the gold standard for HIT measurements, but it is not practical for routine testing or for acute patients, because they are required to wear an uncomfortable contact lens. OBJECTIVE: To develop an easy-to-use video HIT system (vHIT) as a clinical tool for identifying peripheral vestibular deficits. To validate the diagnostic accuracy of vHIT by simultaneous measures with video and search coil recordings across healthy subjects and patients with a wide range of previously identified peripheral vestibular deficits. METHODS: Horizontal HIT was recorded simultaneously with vHIT (250 Hz) and search coils (1,000 Hz) in 8 normal subjects, 6 patients with vestibular neuritis, 1 patient after unilateral intratympanic gentamicin, and 1 patient with bilateral gentamicin vestibulotoxicity. RESULTS: Simultaneous video and search coil recordings of eye movements were closely comparable (average concordance correlation coefficient r(c) = 0.930). Mean VOR gains measured with search coils and video were not significantly different in normal (p = 0.107) and patients (p = 0.073). With these groups, the sensitivity and specificity of both the reference and index test were 1.0 (95% confidence interval 0.69-1.0). vHIT measures detected both overt and covert saccades as accurately as coils. CONCLUSIONS: The video head impulse test is equivalent to search coils in identifying peripheral vestibular deficits but easier to use in clinics, even in patients with acute vestibular neuritis.

Horizontal head impulse test detects gentamicin vestibulotoxicity.

BACKGROUND: Parenteral antibiotic therapy with gentamicin, even in accepted therapeutic doses, can occasionally cause bilateral vestibular loss (BVL) due to hair cell toxicity. OBJECTIVE: To quantify in patients with gentamicin vestibulotoxicity (GVT) the extent of acceleration gain deficit of the horizontal vestibulo-ocular reflex at different accelerations with a graded head impulse test (HIT) in comparison with standard caloric and rotational testing. To characterize the corresponding HIT catch-up saccade pattern to provide the basis for its salience to clinicians. METHODS: Horizontal HIT of graded acceleration (750 degrees-6,000 degrees/sec2) was measured with binocular dual search coils in 14 patients with GVT and compared with 14 normal subjects and a control subject with total surgical BVL. RESULTS: Patients showed mostly symmetric HIT gain deficits with a continuous spectrum from almost normal to complete BVL. Gain deficits were present even at the lowest head accelerations. HIT gain correlated better with caloric (Spearman rho = 0.85, p = 0.0001) than rotational testing (rho = 0.55, p = 0.046). Cumulative amplitude of overt saccades after head impulses was 5.6 times larger in patients than in normal subjects. Compared with previously published patients after unilateral vestibular deafferentation, GVT patients with BVL generated only approximately half the percentage of covert saccades during head rotation (23% at 750 degrees/sec2 to 46% at 6,000 degrees/sec2). CONCLUSIONS: Head impulse testing is useful for early bedside detection of gentamicin vestibulotoxicity because most patients, even those with partial bilateral vestibular loss (BVL), have large overt saccades. Covert saccades, which can conceal the extent of BVL, are only approximately half as frequent as in unilateral patients, but may be present even in total BVL.

Gentamicin vestibulotoxicity impairs human electrically evoked vestibulo-ocular reflex.

BACKGROUND: Electrical vestibular stimulation is believed to directly activate the vestibular afferents to mediate an electrically evoked vestibulo-ocular reflex (eVOR). Gentamicin, an aminoglycoside antibiotic, induces vestibulotoxicity by hair cell damage and death. OBJECTIVE: To determine if human eVOR is impaired by hair cell damage and death in systemic gentamicin vestibulotoxicity (GV). METHODS: Three-dimensional binocular eye movements evoked by bilateral, bipolar, 100 msec direct current-step at intensities of 0.9, 2.5, 5.0, 7.5, and 10.0 mA were recorded with dual-search coils in 12 GV patients, and the results were compared to 13 healthy subjects. RESULTS: Normal eVOR was predominantly torsional, comprising phasic eVOR initiation and cessation acceleration pulses at 9 msec latency after current onset and offset, with a tonic eVOR velocity-step during the 100 msec intervening period of maintained current. Normal phasic eVOR increased, while tonic eVOR scaled linearly, with current intensity. GV impaired phasic eVOR more severely than tonic eVOR, and prolonged the latency to 12-13 msec. In patients without mechanical response to vestibular tests, phasic eVOR was reduced to one-fifth of normal amplitude, doubled in duration, had reduced ability to vary with current intensity, and threshold was increased. Tonic eVOR was reduced to one-third of normal, but still scaled linearly with current intensity. Patients, who retained partial mechanical responses to vestibular tests, had phasic eVOR impairment without tonic eVOR abnormality. CONCLUSION: Impairment of evoked vestibulo-ocular reflex (eVOR) in gentamicin vestibulotoxicity (GV) suggests that vestibular hair cells, activated by electrical stimulation, mediate the eVOR. Abnormalities of the eVOR, especially the phasic component, might be a marker of vestibular injury in GV.

Dynamic aspects of trochlear nerve palsy.

Trochlear nerve palsy leads to kinematic aberrations of both the paretic and the unaffected eye. During dynamic head roll, the rotation axis of the covered paretic or unaffected eye deviates inward, while the rotation axis of the viewing paretic or unaffected eye aligns with the line of sight; this convergence of rotation axes increases with gaze moving in the direction of the unaffected eye. During downward saccades, the trajectories of both eyes curve towards the unaffected side; these curvatures increase when the head is rolled to the affected side and gaze directed to the unaffected side. Hence, during both vestibular evoked and saccadic ocular movements, the unaffected eye shows similar kinematic aberrations as the paretic eye. While aberrations of the paretic eye can be explained by decreased force of the superior oblique (SO) muscle, aberrations of the unaffected eye may be due to increased force parallel to the paretic SO in the unaffected eye in accordance with Hering's law. This law, which forms the basis of conjugate eye movements, also seems to govern eye displacements in unilateral eye muscle palsy.

Head impulse test in unilateral vestibular loss: vestibulo-ocular reflex and catch-up saccades.

BACKGROUND: Quantitative head impulse test (HIT) measures the gain of the angular vestibulo-ocular reflex (VOR) during head rotation as the ratio of eye to head acceleration. Bedside HIT identifies subsequent catch-up saccades after the head rotation as indirect signs of VOR deficit. OBJECTIVE: To determine the VOR deficit and catch-up saccade characteristics in unilateral vestibular disease in response to HIT of varying accelerations. METHODS: Eye and head rotations were measured with search coils during manually applied horizontal HITs of varying accelerations in patients after vestibular neuritis (VN, n = 13) and unilateral vestibular deafferentation (UVD, n = 15) compared to normal subjects (n = 12). RESULTS: Normal VOR gain was close to unity and symmetric over the entire head-acceleration range. Patients with VN and UVD showed VOR gain asymmetry, with larger ipsilesional than contralesional deficits. As accelerations increased from 750 to 6,000 degrees /sec(2), ipsilesional gains decreased from 0.59 to 0.29 in VN and from 0.47 to 0.13 in UVD producing increasing asymmetry. Initial catch-up saccades can occur during or after head rotation. Covert saccades during head rotation are most likely imperceptible, while overt saccades after head rotation are detectable by clinicians. With increasing acceleration, the amplitude of overt saccades in patients became larger; however, initial covert saccades also became increasingly common, occurring in up to about 70% of trials. CONCLUSIONS: Head impulse test (HIT) with high acceleration reveals vestibulo-ocular reflex deficits better and elicits larger overt catch-up saccades in unilateral vestibular patients. Covert saccades during head rotation, however, occur more frequently with higher acceleration and may be missed by clinicians. To avoid false-negative results, bedside HIT should be repeated to improve chances of detection.