Somatotopic disruption of the functional connectivity of the primary sensorimotor cortex in complex regional pain syndrome type 1.

In complex regional pain syndrome (CRPS), the representation area of the affected limb in the primary sensorimotor cortex (SM1) reacts abnormally during sensory stimulation and motor actions. We recorded 3T functional magnetic resonance imaging resting-state data from 17 upper-limb CRPS type 1 patients and 19 healthy control subjects to identify alterations of patients' SM1 function during spontaneous pain and to find out how the spatial distribution of these alterations were related to peripheral symptoms. Seed-based correlations and independent component analyses indicated that patients' upper-limb SM1 representation areas display (i) reduced interhemispheric connectivity, associated with the combined effect of intensity and spatial extent of limb pain, (ii) increased connectivity with the right anterior insula that positively correlated with the duration of CRPS, (iii) increased connectivity with periaqueductal gray matter, and (iv) disengagement from the other parts of the SM1 network. These findings, now reported for the first time in CRPS, parallel the alterations found in patients suffering from other chronic pain conditions or from limb denervation; they also agree with findings in healthy persons who are exposed to experimental pain or have used their limbs asymmetrically. Our results suggest that CRPS is associated with a sustained and somatotopically specific alteration of SM1 function, that has correspondence to the spatial distribution of the peripheral manifestations and to the duration of the syndrome.

Consistency and similarity of MEG- and fMRI-signal time courses during movie viewing.

Movie viewing allows human perception and cognition to be studied in complex, real-life-like situations in a brain-imaging laboratory. Previous studies with functional magnetic resonance imaging (fMRI) and with magneto- and electroencephalography (MEG and EEG) have demonstrated consistent temporal dynamics of brain activity across movie viewers. However, little is known about the similarities and differences of fMRI and MEG or EEG dynamics during such naturalistic situations. We thus compared MEG and fMRI responses to the same 15-min black-and-white movie in the same eight subjects who watched the movie twice during both MEG and fMRI recordings. We analyzed intra- and intersubject voxel-wise correlations within each imaging modality as well as the correlation of the MEG envelopes and fMRI signals. The fMRI signals showed voxel-wise within- and between-subjects correlations up to r = 0.66 and r = 0.37, respectively, whereas these correlations were clearly weaker for the envelopes of band-pass filtered (7 frequency bands below 100 Hz) MEG signals (within-subjects correlation r < 0.14 and between-subjects r < 0.05). Direct MEG-fMRI voxel-wise correlations were unreliable. Notably, applying a spatial-filtering approach to the MEG data uncovered consistent canonical variates that showed considerably stronger (up to r = 0.25) between-subjects correlations than the univariate voxel-wise analysis. Furthermore, the envelopes of the time courses of these variates up to about 10 Hz showed association with fMRI signals in a general linear model. Similarities between envelopes of MEG canonical variates and fMRI voxel time-courses were seen mostly in occipital, but also in temporal and frontal brain regions, whereas intra- and intersubject correlations for MEG and fMRI separately were strongest only in the occipital areas. In contrast to the conventional univariate analysis, the spatial-filtering approach was able to uncover associations between the MEG envelopes and fMRI time courses, shedding light on the similarities of hemodynamic and electromagnetic brain activities during movie viewing.

TMS-EEG responses across the lifespan: Measurement, methods for characterisation and identified responses.

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows probing of the neurophysiology of any neocortical brain area in vivo with millisecond accuracy. TMS-EEG is particularly unique compared with other available neurophysiological methods, as it can measure the state and dynamics of excitatory and inhibitory systems separately. Because of these capabilities, TMS-EEG responses are sensitive to the brain state, and the responses are influenced by brain maturation and ageing, making TMS-EEG a suitable method to study age-specific pathophysiology. In this review, we outline the TMS-EEG measurement procedure, the existing methods used for characterising TMS-EEG responses and the challenges associated with identifying the responses. We also summarise the findings thus far on how TMS-EEG responses change across the lifespan and the TMS-EEG features that separate typical and atypical brain maturation and ageing. Finally, we give an overview of the gaps in current knowledge to provide directions for future studies.

Altered temporal peripapillary retinal flow in patients with disc hemorrhages.

BACKGROUND: To investigate whether any peripapillary retinal blood flow changes are related to disc hemorrhage (DH). METHODS: The study included 21 eyes of 21 patients, of which 14 eyes had glaucoma. All eyes were examined at the time of detection of DH and again 6 months later. Blood flow in the peripapillary retina was measured by scanning laser Doppler flowmetry (Heidelberg Retina Flowmeter), with four adjacent images focused on the peripapillary nerve fiber layer obtained. Retinal perfusion was calculated in arbitrary units by automatic full-field perfusion image analysis. The mean of all four rectangles representing the whole temporal peripapillary retina plus the rectangle representing the area of DH served for analysis. RESULTS: The mean of measurements in all four areas revealed a statistically significant increase in mean flow (MF), systolic flow (SF), and diastolic flow (DF), and a decrease in pulsation index (PI). The rectangle representing the area of DH showed a significant increase in MF, but the SF increase was of borderline significance. Changes in DF and PI did not reach statistical significance. CONCLUSIONS: Results indicate reduced flow at the time of DH and increased flow after resorption.

Blood flow in the peripapillary retina in exfoliation glaucoma.

PURPOSE: The aim of this article is to study peripapillary retinal blood flow in patients with progressive and stable exfoliation glaucoma (ExG). METHODS: Fifty-eight eyes with ExG were included; 25 of them had progressive and 33 stable glaucoma. Retinal blood flow in the peripapillary retina was measured with scanning laser Doppler flowmetry. Acquired flow maps were analysed with the automatic full-field perfusion image analyser. Multiple logistic regression was used to model progression of glaucoma. RESULTS: Mean retinal flow (MF; correlation coefficient, P-value; R = 0.36, P = 0.006) and retinal minimum diastolic flow (R = 0.33, P = 0.011) were positively correlated with visual field mean defect (MD). Factors associated with progressive glaucoma were mean intraocular pressure (OR = 1.198 for each mmHg; P = 0.050) and visual field MD (OR = 1.134 for each dB; P = 0.013). Age (P = 0.35), MF (P = 0.58), or presence of cardiovascular disease (P = 0.17) were not associated with glaucoma progression. CONCLUSION: No difference in peripapillary retinal blood flow between progressive and stable ExG could be found.

Oscillatory TMS-EEG-Responses as a Measure of the Cortical Excitability Threshold.

Transcranial magnetic stimulation (TMS) is a non-invasive tool to perturb brain activity. In TMS studies, the stimulation intensity (SI) is commonly normalized to the resting motor threshold (rMT) that produces muscle responses in 50% of stimulations applied to the motor cortex (M1). Since rMT is influenced by spinal excitability and coil-to-cortex distance, responses recorded from the cortex, instead of a peripheral muscle, could provide a more accurate marker for cortical excitability. Combining TMS with electroencephalography (EEG) enables the measurement of brain-wide cortical reactivity to TMS. We quantified TMS-induced changes in oscillatory power and the phase of EEG with event-related spectral perturbation (ERSP) and inter-trial coherence (ITC). We studied the SI-dependency of ERSP and ITC responses by stimulating the dominant M1 of ten healthy volunteers using single-pulse TMS with 150 pulses at 60%, 80%, 100%, and 120% of rMT. We found SI-dependent ERSP and ITC responses in M1, most notably with the wide-band (8-70 Hz) early ITC responses averaged 20-60 ms after TMS. With approximately linear SI-dependence, the early ITC response was consistent between SIs (intraclass correlation = 0.78, ). Our results reveal the potential of oscillatory EEG responses, in place of rMT, as a measure of the cortical excitability threshold in M1.

An Updated Review on the Most Common Agents Causing Toxic Optic Neuropathies.

BACKGROUND: Toxic optic neuropathies (TONs) often present with a gradual and bilateral decrease in visual acuity, scotomas and optic disc pallor. Obtaining an accurate history is the critical first step in determining the etiology of TONs. METHODS: This updated review contains a thorough analysis of the current PubMed-indexed literature on the most common agents responsible for TONs, including methanol, ethambutol, amiodarone, linezolid, tumor necrosis factor alpha inhibitors and phosphodiesterase 5 inhibitors. RESULTS: The reviewed articles are mainly case reports presenting new and controversial aspects of the above agents. New treatment strategies, such as erythropoietin for methanol optic neuropathy, are being proposed for TONs, a condition that was previously regarded as untreatable. CONCLUSION: TONs could cause significant disability due to visual impairment. In case of early diagnosis and drug withdrawal, most TONs are treatable. Patients need to be appropriately counseled, and prescribing physicians should be especially made aware of TON-inducing medications.

Abnormal Brain Responses to Action Observation in Complex Regional Pain Syndrome.

Patients with complex regional pain syndrome (CRPS) display various abnormalities in central motor function, and their pain is intensified when they perform or just observe motor actions. In this study, we examined the abnormalities of brain responses to action observation in CRPS. We analyzed 3-T functional magnetic resonance images from 13 upper limb CRPS patients (all female, ages 31-58 years) and 13 healthy, age- and sex-matched control subjects. The functional magnetic resonance imaging data were acquired while the subjects viewed brief videos of hand actions shown in the first-person perspective. A pattern-classification analysis was applied to characterize brain areas where the activation pattern differed between CRPS patients and healthy subjects. Brain areas with statistically significant group differences (q < .05, false discovery rate-corrected) included the hand representation area in the sensorimotor cortex, inferior frontal gyrus, secondary somatosensory cortex, inferior parietal lobule, orbitofrontal cortex, and thalamus. Our findings indicate that CRPS impairs action observation by affecting brain areas related to pain processing and motor control. PERSPECTIVE: This article shows that in CRPS, the observation of others' motor actions induces abnormal neural activity in brain areas essential for sensorimotor functions and pain. These results build the cerebral basis for action-observation impairments in CRPS.

The Frequency-Dependent Neuronal Length Constant in Transcranial Magnetic Stimulation.

BACKGROUND: The behavior of the dendritic or axonal membrane voltage due to transcranial magnetic stimulation (TMS) is often modeled with the one-dimensional cable equation. For the cable equation, a length constant λ0 is defined; λ0 describes the axial decay of the membrane voltage in the case of constant applied electric field. In TMS, however, the induced electric field waveform is typically a segment of a sinusoidal wave, with characteristic frequencies of the order of several kHz. OBJECTIVE: To show that the high frequency content of the stimulation pulse causes deviations in the spatial profile of the membrane voltage as compared to the steady state. METHODS: We derive the cable equation in complex form utilizing the complex frequency-dependent representation of the membrane conductivity. In addition, we define an effective length constant λeff, which governs the spatial decay of the membrane voltage. We model the behavior of a dendrite in an applied electric field oscillating at 3.9 kHz with the complex cable equation and by solving the traditional cable equation numerically. RESULTS: The effective length constant decreases as a function of frequency. For a model dendrite or axon, for which λ0 = 1.5 mm, the effective length constant at 3.9 kHz is decreased by a factor 10 to 0.13 mm. CONCLUSION: The frequency dependency of the neuronal length constant has to be taken into account when predicting the spatial behavior of the membrane voltage as a response to TMS.

Hand-held digital video-camera for eye examination and follow-up.

We developed a hand-held digital colour video-camera for eye examination in primary care. The device weighed 550 g. It featured a charge-coupled device (CCD) and corrective optics. Both colour video and digital still images could be taken. The video-camera was connected to a PC with software for database storage, image processing and telecommunication. We studied 88 normal subjects (38 male, 50 female), aged 7-62 years. It was not necessary to use mydriatic eye drops for pupillary dilation. Satisfactory digital images of the whole face and the anterior eye were obtained. The optic disc and the central part of the ocular fundus could also be recorded. Image quality of the face and the anterior eye were excellent; image quality of the optic disc and macula were good enough for tele-ophthalmology. Further studies are needed to evaluate the usefulness of the equipment in different clinical conditions.

Population-based age group specific annual incidence rates of symptomatic age-related macular degeneration.

PURPOSE: To study the population-based annual incidence rates of exudative, dry and all cases of symptomatic age-related macular degeneration (AMD) in different age and sex groups. METHODS: This is a one year, prospective, population-based study on all consecutive new patients with AMD in the hospital district of Central Finland. The diagnosis was confirmed in all patients with slit lamp biomicroscopy, optical coherence tomography (OCT) using a Spectralis HRA + OCT device, and the Heidelberg Eye Explorer 1.6.2.0 program. Fluorescein angiograms were taken when needed. RESULTS: The population-based annual incidence rates of all cases of symptomatic AMD increased from 0.03% (95% CI, 0.01-0.05%) in the age group 50-59 years to 0.82% (95% CI, 0.55-1.09%) in the age group 85-89 years and were 0.2% (95% CI, 0.17-0.24%) in exudative, 0.11% (95% CI, 0.09-0.14%) in dry, and 0.32% (95% CI, 0.28-0.36%) in all cases of AMD in the age group 60 years and older. During the next 20 years in Central Finland the population-based annual incidence rates can be estimated to increase to 0.27% (95% CI, 0.24-0.30%) in exudative, to 0.13% (95% CI, 0.11-0.15%) in dry, and to 0.41% (95% CI, 0.37-0.45%) in all cases of AMD in the age group 60 years and older. The population-based annual incidence of AMD did not show statistically significant differences between males and females (p>0.1). CONCLUSION: The population-based age-group specific annual incidence rates of symptomatic AMD of this study may help to plan health care provision for patients of AMD.

Change in optic nerve head topography in healthy volunteers: an 11-year follow-up.

AIM: To study longitudinal changes in optic nerve head (ONH) topography in healthy volunteers. METHODS: One eye each of 36 healthy volunteers was prospectively followed for 11 (7-13) years with the Heidelberg Retina Tomograph I (HRT I). All eyes had normal visual fields, non-glaucomatous ONHs, no defects on red-free nerve fibre layer photographs and intraocular pressure (IOP) <22 mm Hg. During the follow-up, no eye developed glaucoma; visual fields remained normal, and no longitudinal changes appeared in nerve fibre layers assessed from red-free photographs or ONHs assessed from stereophotographs. The median baseline and follow-up IOPs were comparable (15 mm Hg, range 10-20 mm Hg; and 16 mm Hg; range 10 to 22 mm Hg, respectively; p=0.38). Images were re-evaluated with HRT III and ONHs graded as normal, borderline or glaucomatous with the Moorfield Regression Analysis (MRA). RESULTS Significant changes in HRT parameters indicating increased ONH cupping were detected in cup area (p=0.013), cup-to disc area ratio (p=0.015), rim area (p=0.015), mean cup depth (p=0.006) and cup shape measure (p<0.001). With the MRA classification, nine eyes (9/31, 29%) had changed for the worse in the global or any of the sector classifications. CONCLUSION: Age-dependent changes occur in ONH topography detectable with the HRT.

Digital imaging in differential diagnosis of small choroidal melanoma.

BACKGROUND: To assess the role of digital imaging and a new subtraction method for differential diagnosis of choroidal nevus and small choroidal melanoma. METHODS: Of 241 consecutive patients referred to a tertiary referral center for suspected choroidal melanoma, 110 who underwent digital imaging of the ocular fundus were eligible for this study. Digital color, red-free and red light retinal images were evaluated in a randomized and masked manner and by the subtraction method for diagnosis of the fundus lesion. The reference standard was based on the combined results of ophthalmological examination, including mydriatic ophthalmoscopy, B scan ultrasonography, digital imaging and fluorescein angiography of the ocular fundus. RESULTS: Comparative use of digital color, red-free and red light imaging had 85.7% (95%CI 42.1-99.6) sensitivity, 99.0% (95%CI 94.7-99.9) specificity and 98.2% (95%CI 93.6-99.8) exact agreement versus reference standard in differentiation of small choroidal melanoma from pseudomelanoma. Direct comparison between use of digital images and the reference standard showed excellent agreement in detecting small choroidal melanoma from suspected choroidal lesions (K 0.847; 95%CI 0.639-1.0). The subtraction method was useful to show growth in four of 94 melanocytic choroidal tumors. The mean annual incidence of choroidal melanoma in Southwest Finland was 0.80 per 100.000 population. The most frequent choroidal pseudomelanomas were choroidal melanotic and amelanotic nevi, disciform lesions, congenital hypertrophy of the retinal pigment epithelium, and circumscribed choroidal hemangioma. CONCLUSIONS: Combined use of digital color, red-free and red light imaging was a suitable adjunct in differentiation of small choroidal melanoma from different pseudomelanomas. The subtraction method may reveal early growth of the melanotic choroidal tumors.

Endophthalmitis following cataract surgery in southwest Finland from 1987 to 2000.

PURPOSE: To investigate the incidence, causes, prevention, treatment and outcome of postoperative endophthalmitis (POE) following cataract surgery in southwest Finland from 1987 to 2000. METHODS: We reviewed the medical records of all patients with POE following cataract surgery treated in the hospital district of Southwest Finland from 1 January 1987 to 31 December 2000. Population-based annual incidence rates of cataract extractions and POE were calculated using the corrected population statistics of the hospital district. RESULTS: There were 29,350 cataract procedures during the 14-year period. POE developed in 47 patients. The annual incidence of cataract operations increased more than fivefold from 1987 (155 per 100,000 population) to the maximum in 1999 (930 per 100,000 population), whereas the annual incidence of postcataract endophthalmitis decreased from the maximum of 11.1 per 1,000 cataract extractions (1.91 per 100,000 population) in 1988 to the minimum of 0-0.6 per 1,000 cataract extractions in 1999 and 2000. POE occurred statistically significantly more frequently after extracapsular cataract extraction (ECCE) than after phacoemulsification (Phaco) (P=0.0006). Gram-positive bacteria were the most frequent cause of acute POE and Propionibacterium acnes was the most frequent reason for delayed-onset POE. The complications of POE after cataract surgery included visual loss to below 0.05 (25.5% of affected eyes), opacification of the cornea (21.3%), secondary cataract (40.4%), increase in intraocular pressure (29.8%), vitreous clouding (63.8%), and retinal detachment (6.4%). Nearly one half of the eyes achieved final visual acuity of 0.5 or better. CONCLUSIONS: During the 14-year study period there was a shift from ECCE to Phaco, a fivefold increase in cataract extractions, and a decrease in the annual incidence of POE from 5.5-11.1 to 0-0.6 per 1,000 operations. Phaco was associated with a lower risk of POE than ECCE.

Group IIA phospholipase A(2) concentration of tears in patients with ocular rosacea.

PURPOSE: To determine the concentration of group IIA phospholipase A(2) (GIIAPLA(2)) in tears of patients with ocular rosacea, and to compare it with GIIAPLA(2) concentration in tears of age-matched healthy controls. METHODS: The GIIAPLA(2) concentration in tears was measured with a time-resolved fluoroimmunoassay in 21 patients with ocular rosacea (mean age 55.6+/-9.2 years) and in 21 normal subjects (mean age 53.4+/-8.2 years). Conjunctival brush cytology was carried out and eosinophils, neutrophils, lymphocytes, squamous epithelial cells, columnar epithelial cells, metaplastic changes and goblet cells were calculated separately. RESULTS: The GIIAPLA (2) concentration in tears was statistically significantly lower in patients with ocular rosacea (31.0+/-18.4 microg/ml, p=0.0099) and, more specifically, in patients who had dry eye (25.8+/-15.1 microg/ml, p=0.0034), compared to that in normal controls. There was no correlation between the GIIAPLA (2) content of tears and the conjunctival cells collected by the brush cytology. CONCLUSION: The tears of patients with dry eye symptoms due to ocular rosacea have decreased GIIAPLA (2) content. The pathogenic importance of this finding is discussed.

Sensitivity and specificity of digital retinal images in grading diabetic retinopathy.

PURPOSE: To assess three novel digital fundus cameras for diabetic retinopathy (DR) screening. METHODS: Digital colour and red-free retinal imaging (Topcon TRC 50 IA, Canon CR6-45NM, and MediTell) was used to capture 427 images of 70 diabetes patients and control subjects. The images were graded for DR by three readers in a randomized and masked manner using a modified Early Treatment Diabetic Retinopathy Study classification. The reference standard was based on mydriatic ophthalmoscopy and colour and red-free images. RESULTS: Digital 50 degrees red-free imaging had sensitivity of 97.7%, two-field 50 degrees colour imaging 94.0%, and two-field 45 degrees colour imaging sensitivity of 88.9%. The specificity of these imaging modalities was 98.9-100%, and ungradeable images represented 1.2-1.6%. The hand-held digital colour videocamera (MediTell) showed a sensitivity of 6.9% and ungradeable images represented 92.3%. CONCLUSION: Digital 50 degrees red-free and two-field 50 degrees or 45 degrees colour imaging were suitable for DR screening, whereas the hand-held digital videocamera did not fulfil the needs of DR screening.

Group IIA phospholipase A2 content of tears in patients with atopic blepharoconjunctivitis.

BACKGROUND: To determine the concentration of group IIA phospholipase A(2) (GIIAPLA(2)) in tears of patients with atopic blepharoconjunctivitis (ABC), and to compare it with the GIIAPLA(2) concentration of tears in age-matched healthy controls. METHODS: The diagnosis of ABC was confirmed with a positive skin prick test and the presence of atopic dermatitis in lids. Conjunctival brush cytology was taken, and the cells including eosinophils, neutrophils, lymphocytes, squamous epithelial cells, columnar epithelial cells, metaplastic changes and the goblet cells were calculated separately. The GIIAPLA(2) concentration of tears was measured with a time-resolved fluoroimmunoassay in 29 patients with ABC (mean age 36.3+/-12.7 years) and 29 normal subjects (mean age 37.0+/-12.0 years). RESULTS: The GIIAPLA(2) concentration of tears in patients with ABC was 43.8+/-33.0 microg/ml, and in normal subjects it was 67.1+/-23.3 microg/ml. The difference was statistically significant (p=0.0018). The concentration of GIIAPLA(2) of tears was lowest in the subgroup of patients with ABC and dry eye (25.8()+/-23.6 microg/ml), whereas it was only slightly decreased in patients with ABC and normal tear secretion (56.6+/-33.3 microg/ml). The difference between these two subgroups was statistically significant (p=0.011). There was no statistically significant correlation between the GIIAPLA(2) concentration of tears and the quantity of different conjunctival cells gathered by the brush cytology. However, an almost significant correlation was found between the GIIAPLA(2) concentration in tears and conjunctival eosinophils. CONCLUSIONS: The results indicate that in patients with ABC the GIIAPLA(2) content of tears was decreased, without any dependence on the quantity of different conjunctival cells.