Perinatal exposure to the immune-suppressant di-n-octyltin dichloride affects brain development in rats.

Disruption of the immune system during embryonic brain development by environmental chemicals was proposed as a possible cause of neurodevelopmental disorders. We previously found adverse effects of di-n-octyltin dichloride (DOTC) on maternal and developing immune systems of rats in an extended one-generation reproductive toxicity study according to the OECD 443 test guideline. We hypothesize that the DOTC-induced changes in the immune system can affect neurodevelopment. Therefore, we used in-vivo MRI and PET imaging and genomics, in addition to behavioral testing and neuropathology as proposed in OECD test guideline 443, to investigate the effect of DOTC on structural and functional brain development. Male rats were exposed to DOTC (0, 3, 10, or 30 mg/kg of diet) from 2 weeks prior to mating of the F0-generation until sacrifice of F1-animals. The brains of rats, exposed to DOTC showed a transiently enlarged volume of specific brain regions (MRI), altered specific gravity, and transient hyper-metabolism ([18F]FDG PET). The alterations in brain development concurred with hyper-responsiveness in auditory startle response and slight hyperactivity in young adult animals. Genomics identified altered transcription of key regulators involved in neurodevelopment and neural function (e.g. Nrgrn, Shank3, Igf1r, Cck, Apba2, Foxp2); and regulators involved in cell size, cell proliferation, and organ development, especially immune system development and functioning (e.g. LOC679869, Itga11, Arhgap5, Cd47, Dlg1, Gas6, Cml5, Mef2c). The results suggest the involvement of immunotoxicity in the impairment of the nervous system by DOTC and support the hypothesis of a close connection between the immune and nervous systems in brain development.

Reliability, construct and concurrent validity of a smartphone-based cognition test in multiple sclerosis.

BACKGROUND: Early detection and monitoring of cognitive dysfunction in multiple sclerosis (MS) may be enabled with smartphone-adapted tests that allow frequent measurements in the everyday environment. OBJECTIVES: The aim of this study was to determine the reliability, construct and concurrent validity of a smartphone-adapted Symbol Digit Modalities Test (sSDMT). METHODS: During a 28-day follow-up, 102 patients with MS and 24 healthy controls (HC) used the MS sherpa® app to perform the sSDMT every 3 days on their own smartphone. Patients performed the Brief International Cognitive Assessment for MS at baseline. Test-retest reliability (intraclass correlation coefficients, ICC), construct validity (group analyses between cognitively impaired (CI), cognitively preserved (CP) and HC for differences) and concurrent validity (correlation coefficients) were assessed. RESULTS: Patients with MS and HC completed an average of 23.2 (SD = 10.0) and 18.3 (SD = 10.2) sSDMT, respectively. sSDMT demonstrated high test-retest reliability (ICCs > 0.8) with a smallest detectable change of 7 points. sSDMT scores were different between CI patients, CP patients and HC (all ps < 0.05). sSDMT correlated modestly with the clinical SDMT (highest r = 0.690), verbal (highest r = 0.516) and visuospatial memory (highest r = 0.599). CONCLUSION: Self-administered smartphone-adapted SDMT scores were reliable and different between patients who were CI, CP and HC and demonstrated concurrent validity in assessing information processing speed.

Real-world keystroke dynamics are a potentially valid biomarker for clinical disability in multiple sclerosis.

BACKGROUND: Clinical measures in multiple sclerosis (MS) face limitations that may be overcome by utilising smartphone keyboard interactions acquired continuously and remotely during regular typing. OBJECTIVE: The aim of this study was to determine the reliability and validity of keystroke dynamics to assess clinical aspects of MS. METHODS: In total, 102 MS patients and 24 controls were included in this observational study. Keyboard interactions were obtained with the Neurokeys keyboard app. Eight timing-related keystroke features were assessed for reliability with intraclass correlation coefficients (ICCs); construct validity by analysing group differences (in fatigue, gadolinium-enhancing lesions on magnetic resonance imaging (MRI), and patients vs controls); and concurrent validity by correlating with disability measures. RESULTS: Reliability was moderate in two (ICC = 0.601 and 0.742) and good to excellent in the remaining six features (ICC = 0.760-0.965). Patients had significantly higher keystroke latencies than controls. Latency between key presses correlated the highest with Expanded Disability Status Scale (r = 0.407) and latency between key releases with Nine-Hole Peg Test and Symbol Digit Modalities Test (ρ = 0.503 and r = -0.553, respectively), ps < 0.001. CONCLUSION: Keystroke dynamics were reliable, distinguished patients and controls, and were associated with clinical disability measures. Consequently, keystroke dynamics are a promising valid surrogate marker for clinical disability in MS.

Neuroprotective effects of exercise in people with progressive multiple sclerosis (Exercise PRO-MS): study protocol of a phase II trial.

BACKGROUND: Neurodegeneration, rather than inflammation, plays a key role in the progressive phase of multiple sclerosis (MS). Current disease modifying treatment options for people with progressive MS (PMS) do not specifically target neurodegeneration. Preliminary evidence suggests that exercise therapy might have neuroprotective effects. However, neuroprotective effect studies of exercise interventions in PMS are scarce and the possible mode of action underlying neuroprotective effects of exercise are unknown and need to be elucidated. The main aim of this phase II trial is to assess whether progressive resistance training (PRT) and high intensity interval training (HIIT), can slow down neurodegeneration in people with PMS. METHODS: In a single-blinded phase II clinical trial with an extended baseline period, 60 people with PMS will be randomly assigned to PRT or HIIT. The participants should have had a relapse onset of MS with confirmed disease progression, however still ambulatory. The duration of the study is 48 weeks, consisting of 16 weeks baseline period (no intervention), 16 weeks intervention and 16 weeks follow-up. Patient-tailored training will be performed 3 times per week for one hour in groups, led by an experienced physiotherapist. The primary outcome measure is neurodegeneration, measured as whole brain atrophy on magnetic resonance imaging (MRI). Secondary outcome parameters will include other biomarkers associated with neurodegeneration (i.e. regional brain atrophy, lesion load, white matter integrity, resting state functional connectivity, blood biomarkers (brain derived neurotrophic factor (BDNF) and serum neurofilament light (sNFL)), patient functioning (physical and cognitive) and cardiovascular risk factors. DISCUSSION: Besides the primary outcome measures, this study will examine a large variety of biomarkers associated with neurodegeneration after an exercise intervention. Combining outcome parameters may help to elucidate the mode of action underlying neuroprotective effects of exercise. TRIAL REGISTRATION: This trial is prospectively registered at the Dutch Trial Registry (number NL8265, date 06-01-2020).

Three distinct physical behavior types in fatigued patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis often leads to fatigue and changes in physical behavior (PB). Changes in PB are often assumed as a consequence of fatigue, but effects of interventions that aim to reduce fatigue by improving PB are not sufficient. Since the heterogeneous nature of MS related symptoms, levels of PB of fatigued patients at the start of interventions might vary substantially. Better understanding of the variability by identification of PB subtypes in fatigued patients may help to develop more effective personalized rehabilitation programs in the future. This study aimed to identify PB subtypes in fatigued patients with multiple sclerosis based on multidimensional PB outcome measures. METHODS: Baseline accelerometer (Actigraph) data, demographics and clinical characteristics of the TREFAMS-ACE participants (n = 212) were used for secondary analysis. All patients were ambulatory and diagnosed with severe fatigue based on a score of ≥35 on the fatigue subscale of the Checklist Individual Strength (CIS20r). Fifteen PB measures were used derived from 7 day measurements with an accelerometer. Principal component analysis was performed to define key outcome measures for PB and two-step cluster analysis was used to identify PB types. RESULTS: Analysis revealed five key outcome measures: percentage sedentary behavior, total time in prolonged moderate-to-vigorous physical activity, number of sedentary bouts, and two types of change scores between day parts (morning, afternoon and evening). Based on these outcomes three valid PB clusters were derived. CONCLUSIONS: Patients with severe MS-related fatigue show three distinct and homogeneous PB subtypes. These PB subtypes, based on a unique set of PB outcome measures, may offer an opportunity to design more individually-tailored interventions in rehabilitation. TRIAL REGISTRATION: Clinical trial registration no ISRCTN 82353628 , ISRCTN 69520623  and  ISRCTN 58583714 .

Myospherulosis as a complication of functional endoscopic sinus surgery: a double case report.

INTRODUCTION: Paraffinomas (also known as 'sclerosing lipogranulomas' or 'myospherulosis') are a widely acknowledged complication of cosmetic paraffin injections but they are rare following functional endoscopic sinus surgery. CASE PRESENTATIONS: Our first case features a 45-year-old woman presenting with a peri-ocular swelling two weeks after functional endoscopic sinus surgery. The procedure was complicated by a fractured lamina papyracea. A nasal packing with antibiotic ointment was left in situ. Initially, the inflammation was controlled successfully with corticosteroids but the swelling persists to this day. Our second case is a 45-year-old man who suffered from a recurrent swelling of the right eyelid after endoscopic sinus surgery. Multiple treatments with oral antibiotics and corticosteroids brought about no improvement. Debulking surgery was performed and a PDS film was placed between the peri-orbita and the bony orbital floor but the swelling recurred. The patient finally consulted a plastic surgeon as a last resort, but the reconstructive procedure only exacerbated the clinical picture. In both cases a biopsy was performed which established the foreign body reaction typical of a paraffinoma. At present, both patients still suffer from this condition. CONCLUSION: The complete resection of a paraffinoma is seldom possible because of diffuse infiltration and recurrence is very likely. We therefore conclude that paraffin-based ointments should not be used with nasal packing after sinus surgery, especially when there has been a lesion involving the orbital wall.

The relation between cognitive-behavioural responses to symptoms in patients with long term medical conditions and the outcome of cognitive behavioural therapy for fatigue - A secondary analysis of four RCTs.

BACKGROUND: Cognitive behavioural therapy (CBT) is effective in reducing fatigue across long-term conditions (LTCs). This study evaluated whether cognitive and behavioural responses to symptoms: 1) differ between LTCs and 2) moderate and/or mediate the effect of CBT on fatigue. METHOD: Data were used from four Randomized Controlled Trials testing the efficacy of CBT for fatigue in Chronic Fatigue Syndrome/ME (N = 240), Multiple Sclerosis (N = 90), Type 1 Diabetes Mellitus (N = 120) and Q-fever fatigue syndrome (N = 155). Fatigue severity, assessed with the Checklist Individual Strength, was the primary outcome. Differences in fatigue perpetuating factors, assessed with the Cognitive Behavioural Responses to Symptoms Questionnaire (CBRQ), between diagnostic groups were tested using ANCOVAs. Linear regression and mediation analyses were used to investigate moderation and mediation by CBRQ scores of the treatment effect. RESULTS: There were small to moderate differences in CBRQ scores between LTCs. Patients with higher scores on the subscales damage beliefs and avoidance/resting behaviour at baseline showed less improvement following CBT, irrespective of diagnosis. Reduction in fear avoidance, catastrophising and avoidance/resting behaviour mediated the positive effect of CBT on fatigue across diagnostic groups. DISCUSSION: The same cognitive-behavioural responses to fatigue moderate and mediate treatment outcome across conditions, supporting a transdiagnostic approach to fatigue.

Effect of time of day on walking capacity and self-reported fatigue in persons with multiple sclerosis: a multi-center trial.

BACKGROUND: Many persons with multiple sclerosis (PwMS) report increased fatigue in the afternoon and evening compared with the morning. It is commonly accepted that physical capacity also decreases as time of day progresses, potentially influencing the outcomes of testing. OBJECTIVE: The objective of this article was to determine whether self-reported fatigue level and walking capacity are influenced by time of day in PwMS. METHODS: A total of 102 PwMS from 8 centers in 5 countries, with a diverse level of ambulatory dysfunction (Expanded Disability Status Scale [EDSS] <6.5), participated. Patients performed walking capacity tests and reported fatigue level at three different time points (morning, noon, afternoon) during 1 day. Walking capacity was measured with the 6-Minute Walk Test (6MWT) and the 10-m walk test performed at usual and fastest speed. Self-reported fatigue was measured by the Rochester Fatigue Diary (RFD). Subgroups with mild (EDSS 1.5-4.0, n = 53) and moderate (EDSS 4.5-6.5, n = 49) ambulatory dysfunction were formed, as changes during the day were hypothesized to depend on disability status. RESULTS: Subgroups had different degree of ambulatory dysfunction (p < 0.001) but reported similar fatigue levels. Although RFD scores were affected by time of day with significant differences between morning and noon/afternoon (p < 0.0001), no changes in walking capacity were found in any subgroup. Additional analyses on subgroups distinguished by diurnal change in self-reported fatigue failed to reveal analogous changes in walking capacity. CONCLUSIONS: Testing of walking capacity is unaffected by time of day, despite changes in subjective fatigue.

Self-regulation as rehabilitation outcome: what is important according to former patients?

PURPOSE: Self-regulation refers to self-management and self-control, with or without disability. Outcomes of rehabilitation with respect to self-regulation are unclear. This study aims to identify elements of self-regulation that former patients consider important in the context of medical rehabilitation. MATERIALS AND METHODS: Qualitative exploration based on focus group discussions (FGDs). Transcripts were analysed using thematic analysis as well as open coding. Forty individuals participated in seven diagnosis-related FGDs. RESULTS: Six subthemes were raised in the FGDs which could be merged into three main themes. Two main themes are conditional for regaining self-regulation: 1) having insight into one's condition and abilities (i.e., insight into impairments. consequences of impairments. abilities); 2) to know how to cope with the consequences of the condition (be able to communicate limitations; have to trust in body and functioning). The subject of the last theme 3) is how to apply self-regulation in one's own life (to make use of abilities and optimize functioning). CONCLUSIONS: Three main themes of self-regulation in the context of medical rehabilitation were identified by former patients, partly relating to the ability to self-regulate and partly to the execution of self-regulation. This knowledge can be used to define specific rehabilitation goals and further develop rehabilitation outcome measurement.IMPLICATIONS FOR REHABILITATIONAwareness of the fundamental subthemes of self-regulation in rehabilitation will positively contribute to theory building and improve clinical practice (e.g., goal setting).Paying explicit attention to the six subthemes as standard elements of rehabilitation will help to provide a comprehensive view concerning self-regulation.The conceptual model of self-regulation, based on patient perspectives, can contribute to the measurement of rehabilitation outcomes.

Community walking can be assessed using a 10-metre timed walk test.

BACKGROUND: A decline in mobility is a common feature of multiple sclerosis (MS). Community walking scales are used to categorize patients in their ability to move independently. The first purpose of this study was to determine which specific gait speed corresponded with the categories of the Modified Functional Walking Categories (MFWC). The second purpose was to determine the Minimally Important Change (MIC) in absolute gait speed using the MFWC and Expanded Disability Status Scale (EDSS) as external criteria. METHOD: MS patients were measured six times in 6 years. Gait velocity was measured with the 10-metre timed walk test (10-m TWT), the severity of MS was determined with the EDSS, and community walking was assessed with the MFWC. For each category of the MFWC, Receiver Operating Characteristic (ROC) curves were used to find the best possible cut-off point on the 10-m TWT. The MIC in absolute gait speed was determined using a change of one category on the MFWC or one point on the EDSS. RESULTS: A strong relationship was found between gait speed and the MFWC; all areas under the ROC curves (AUCs) were between 0.74 and 0.86. The MIC in absolute gait speed could not be determined, because the AUCs were below the threshold of 0.70 and changes in gait speed were small. CONCLUSIONS: Gait speed is related to community walking, but an MIC in absolute gait speed could not be determined using a minimally important change on the MFWC or the EDSS as external criteria.

Ten-year disease progression in multiple sclerosis: walking declines more rapidly than arm and hand function.

BACKGROUND AND AIMS: From a clinical perspective there is a difference in the decline of arm and hand function and leg function in patients with multiple sclerosis (PwMS). Therefore, this study investigated the course of walking and arm and hand functions in PwMS over the first 10 years after diagnosis, including whether any function declined earlier or faster. METHODS: A long-term prospective follow-up study of an incidence cohort of 156 patients with a definite diagnosis of MS, either non-relapse onset (n=28) or relapse onset (n=128) type. Participants were systematically examined immediately after definite diagnosis, at 6 months, and at 1, 2, 3, 6 and 10 years. Walking was determined with the fast 10-meter timed walk test (10mTWT), arm and hand function with the Action Research Arm test (ARAT) and the nine-hole peg test (9HPT). The 10-year trajectories of walking and arm and hand functions were compared using standardized z-scores. RESULTS: From 3 years onwards the z-scores of the arm and leg function were visually diverging, with a trend towards significance at 6 years, and at 10 years the 10mTWT z-score is significantly higher than the 9HPT. This difference is more pronounced in non-relapse onset patients than in patients with relapse onset type MS, but present in both groups over the first 10 years. In the non-relapse onset group a difference in z-scores at 10 years post-diagnosis between the 10m TWT and 9HPT was found of -12.94 (95% confidence interval (CI) -20.2 to -5.73) for the right and -10.14 (95% CI -17.3 to -2.93) for the left hand. In the relapse onset group there was a difference at 10 years post-diagnosis of -2.17 (95% CI -3.75 to -0.59) for the right and a difference of -2.29 (95% CI -3.87 to -0.71) for the left hand. CONCLUSION: This is the first longitudinal study that shows that walking declines earlier and more rapidly than arm and hand function in patients with MS. These results give important insights that can be linked to the pathophysiological disease process regarding the ascending order of deterioration in patients with MS.

Eye diseases in patients with sleep apnea syndrome: a rewiew.

Sleep apnea syndrome (SAS) is characterized by recurrent episodes of apnea during sleep. Mechanical upper airway obstruction is by far the most frequent form of SAS, and is named obstructive sleep apnea (OSA). Besides giving rise to a reduced quality of life, OSA is associated with important cardiovascular morbidity and mortality if left untreated. OSA has also been associated with several ophthalmic manifestations. The purpose of this paper is to review the most important features of OSA, and to highlight the ophthalmic abnormalities recognized in these patients. Ophthalmologists should be familiar with the possibility of sleep disorders in their patients as the cause of certain eye pathologies. The ophthalmologist can often identify a patient with OSA and refer him for a sleep study. Sleep physicians, on the other hand, should be alert for the possibility of eye disorders, inform their patients and refer them for a check up.

Conjunctival Leiomyosarcoma, a Rare Neoplasm Always Originating at the Limbus? Report of a New Case and Review of 11 Published Cases.

PURPOSE OF THE STUDY: To describe the differential diagnosis and management of a rare conjunctival malignancy. PROCEDURES: A 79-year-old man presented with a conjunctival mass at the limbus. Excisional biopsy revealed a malignant mesenchymal tumor with myogenic differentiation. Six months later, three suspect lesions developed at the border of the previous excision. Pathological diagnosis pointed to a leiomyosarcoma. Adjuvant radiotherapy with strontium-90 brachytherapy was applied. After 3 years, there was neither recurrence nor distant metastases. A literature review revealed 11 cases of conjunctival leiomyosarcoma. RESULTS: All 12 cases seemed to originate at the limbal conjunctiva. Scleral invasion was found only in one patient with multiple previous resections. Corneal invasion was reported in two patients. Four patients had a globe-sparing resection. In two of them, margins were not tumor free and additional brachytherapy gave a tumor-free follow-up of 1 and 3 years. Four cases underwent an exenteration. CONCLUSION AND MESSAGE: Primary conjunctival leiomyosarcoma is a rare tumor with a favorable prognosis due to early detection and consequently limited size. Diagnosis involves histopathological investigation including immunohistochemistry. If possible, complete resection has the best prognosis. Adjunctive radiotherapy can be effective when the margins are not free and should be considered.

Predicting short-term disability progression in early multiple sclerosis: added value of MRI parameters.

OBJECTIVE: Magnetic resonance imaging (MRI) and clinical parameters are associated with disease progression in multiple sclerosis (MS). The aim of this study was to investigate whether adding MRI parameters to a model with only clinical parameters could improve these associations. METHODS: 89 patients (55 women) with recently diagnosed MS had clinical and MRI evaluation at baseline (time of diagnosis) and at follow-up after 2.2 years. Detailed clinical data were available, including disease type (relapse-onset or progressive-onset) and disability, as measured by the Expanded Disability Status Scale (EDSS). MRI parameters included Normalised Brain Volume (NBV) at baseline, percentage brain volume change (PBVC/year), T2- and T1-lesion loads and spinal cord abnormalities. Progression of disability (increase in EDSS of at least 1 point at follow-up) was the main outcome measure. For a model containing only clinical parameters, the added value of MRI parameters was tested using logistic regression. RESULTS: PBVC/year and lesion loads at follow-up were significantly higher in the group with progression. Adding PBVC/year to a clinical model improved the model, indicating that MRI parameters added independent information (p<0.001). CONCLUSION: The rate of cerebral atrophy conveys added information for the progression of disability in patients with early MS, suggesting that clinical disability is determined by neurodegenerative changes as depicted by MRI.

Cognitive behavioural therapy for MS-related fatigue explained: A longitudinal mediation analysis.

BACKGROUND: Cognitive behavioural therapy (CBT) effectively reduces fatigue directly following treatment in patients with Multiple Sclerosis (MS), but little is known about the process of change during and after CBT. DESIGN: Additional analysis of a randomized clinical trial. OBJECTIVE: To investigate which psychological factors mediate change in fatigue during and after CBT. METHODS: TREFAMS-CBT studied the effectiveness of a 16-week CBT treatment for MS-related fatigue. Ninety-one patients were randomized (44 to CBT, 47 to the MS-nurse consultations). Mediation during CBT treatment was studied using assessments at baseline, 8 and 16weeks. Mediation of the change in fatigue from post-treatment to follow-up was studied separately using assessments at 16, 26 and 52weeks. Proposed mediators were: changes in illness cognitions, general self-efficacy, coping styles, daytime sleepiness, concentration and physical activity, fear of disease progression, fatigue perceptions, depression and physical functioning. Mediators were separately analysed according to the product-of-coefficients approach. Confidence intervals were calculated with a bootstrap procedure. RESULTS: During treatment the decrease in fatigue brought on by CBT was mediated by improved fatigue perceptions, increased physical activity, less sleepiness, less helplessness, and improved physical functioning. Post-treatment increases in fatigue levels were mediated by reduced physical activity, reduced concentration, and increased sleepiness. CONCLUSION: These results suggests that focusing on improving fatigue perceptions, perceived physical activity, daytime sleepiness, helplessness, and physical functioning may further improve the effectiveness of CBT for fatigue in patients with MS. Maintenance of treatment effects may be obtained by focusing on improving physical activity, concentration and sleepiness.

The usefulness of evaluative outcome measures in patients with multiple sclerosis.

To select the most useful evaluative outcome measures for early multiple sclerosis, we included 156 recently diagnosed patients in a 3-year follow-up study, and assessed them on 23 outcome measures in the domains of disease-specific outcomes, physical functioning, mental health, social functioning and general health. A global rating scale (GRS) and the Expanded Disability Status Scale (EDSS) were used as external criteria to determine the minimally important change (MIC) for each outcome measure. Subsequently, we determined whether the outcome measures could detect their MIC reliably. From these, per domain the outcome measure that was found to be most sensitive to changes (responsive) was identified. At group level, 11 outcomes of the domains of physical functioning, mental health, social functioning and general health could reliably detect the MIC. Of these 11, the most responsive measures per domain were the Medical Outcome Study 36 Short Form sub-scale physical functioning (SF36pf), the Disability and Impact Profile (DIP) sub-scale psychological, the Rehabilitation Activities Profile sub-scale occupation (RAPocc) and the SF36 sub-scale health, respectively. Overall, the most responsive measures were the SF36pf and the RAPocc. In individual patients, none of the measures could reliably detect the MIC. In sum, in the early stages of multiple sclerosis the most useful evaluative outcome measures for research are the SF36pf (physical functioning) and the RAPocc (social functioning).

[Secondary cataract: a problem resolved]. / La cataracte secondaire: un problème résolu.

A new intraocular lens (LOL) aiming at eradicating posterior capsule opacification (PCO), the most common complication after cataract surgery, is proposed. The haptics of this new IOL are conceived to capture the remaining lens epithelial cells (LECs) left behind in the capsular equator after cataract surgery in a closed area in order not to allow them to proliferate into the visual axis. In order to facilitate the surgical technique, several devices have been developed. We showed the inocuity of this technique on postoperative inflammation and the low rate of postoperative complications. We obtained 0% PCO and in addition excellent refractive results. The results on children and babies were the most rewarding since none of these children presented PCO and accommodation was important enough as to allow reading without glasses.

Searching the way out for posterior capsule opacification.

Searching the way out for posterior capsule opacification was one of our goals in improving current cataract surgery techniques. The second goals was restoring accommodation but this goal prooved to remain unsolved. The bag-in-the-lens concept of IOL and implantation technique has been used in 271 patients of which 15 children. These patients have a follow-up of one month to 5 years. The optical axis of all these patients remained crystal clear, which allows us to conclude that the problem of PCO is solved by the bag-in-the-lens implantation concept. These very encouraging results inspired us to new ideas, which will receive priority in our research: accommodation and optimising the quality of vision by compensating for the ocular aberrations.

MS functional composite: relation to disease phenotype and disability strata.

OBJECTIVE: The MS Functional Composite (MSFC), a recently developed outcome measure for clinical trials, was applied to 240 patients with MS to explore its utility in different subgroups of MS and for comparison with the Expanded Disability Status Scale (EDSS). METHOD: Three clinical dimensions were examined: arm/hand function, leg function/ambulation, and cognition. Predictions of relative scores on the MSFC and its components in three major MS phenotypes (relapsing-remitting, primary progressive, and secondary progressive) and three strata of disability were developed and tested. Also, correlations with EDSS were calculated and the effect of an external reference population was assessed. RESULTS: Mean MSFC score was positive in the relapsing-remitting (0.4) and mildly disabled (0.4) groups and negative in the secondary progressive (-0.3), primary progressive (-0.4), and moderately (-0.07) and severely disabled (-1.0) groups. The correlation between EDSS and MSFC was strong (-0.68). EDSS correlated strongly with ambulation in secondary and primary progressive patients and severely disabled patients, moderately with arm/hand function for all analyzed groups, and not at all with cognition. Comparison with an external reference population showed changes in MSFC- and Z-scores, but did not result in altered differences between the subgroups. CONCLUSION: Our prospective study in subgroups of MS confirmed and extended the construct validity of the MSFC. The MSFC also showed good concurrent validity with the EDSS, and includes information about cognition.