Auditing the frequency and the clinical and economic impact of testing for Fabry disease in patients under the age of 70 with a stroke admitted to Saint Vincent's University Hospital over a 6-month period.

BACKGROUND: Fabry disease is an X-linked recessive lysosomal storage disorder that provokes multi-organ morbidity, including early-onset stroke. Worldwide prevalence may be greater than previously estimated, with many experiencing first stroke prior to diagnosis of Fabry disease. AIMS: The aim of this study is to screen a cohort of stroke patients under 70 years of age, evaluating the clinical and economic efficacy of such a broad screening programme for Fabry disease. METHODS: All stroke patients under 70 years of age who were entered into the Saint Vincent's University Hospital stroke database over a 6-month period underwent enzyme analysis and/or genetic testing as appropriate for Fabry disease. Patients' past medical histories were analysed for clinical signs suggestive of Fabry disease. Cost-effectiveness analysis of testing was performed and compared to overall economic impact of young stroke in Ireland. RESULTS: Of 22 patients tested for Fabry disease, no new cases were detected. Few clinical indicators of Fabry disease were identified at the time of testing. CONCLUSION: Broad screening programmes for Fabry disease are highly unlikely to offset the cost of testing. The efficacy of future screening programmes will depend on careful selection of an appropriate patient cohort of young stroke patients with multi-organ morbidity and a positive family history.

Visualisation of the medial longitudinal fasciculus using fibre tractography in multiple sclerosis patients with internuclear ophthalmoplegia.

BACKGROUND: This study investigates the use of fibre tractography to facilitate visualisation of the medial longitudinal fasciculus (MLF) and the impact of internuclear ophthalmoplegia (INO) causing lesions on these reconstructions of the tract. Improved visualisation of such tracts may improve knowledge, understanding and confidence related to neurological conditions. AIMS: To explore the use of fibre tractography for the visualisation of the MLF in patients with INO. METHODS: Twelve MS subjects with clinical evidence of INO and 12 matched controls underwent magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), of the brain. Fibre tractography reconstructions were then evaluated and validated by an experienced neuroanatomist. RESULTS: The evaluating neuroanatomist confirmed that the MLF had been reproduced in all of the reconstructed cases (fibre tractography was unsuccessful in five cases). The sensitivity of fibre tractography to MLF pathology was 58.3 % while the specificity was much higher at 85.7 % with a positive predictive value of 87.5 % and a negative predictive value of 54.6 %, with excellent intra-reader reliability. CONCLUSION: This study demonstrates that fibre tractography of the MLF can potentially be performed with a view to facilitating improved visualisation of the tract and associated pathology in cases of INO. This may help explain the association between lesion type and location with clinical symptomatology and may assist in monitoring disease progression. These reconstructions may provide a valuable addition to the teaching and understanding of clinical signs related to subtle pathology.

Diagnostic Efficacy of Conventional MRI Pulse Sequences in the Detection of Lesions Causing Internuclear Ophthalmoplegia in Multiple Sclerosis Patients.

PURPOSE: The purpose of this study was to investigate the diagnostic efficacy of a range of conventional magnetic resonance imaging (MRI) pulse sequences in the identification of internuclear ophthalmoplegia (INO) caused by medial longitudinal fasciculus (MLF) lesions in multiple sclerosis patients using a receiver-operating characteristic (ROC) methodology. METHODS: A total of 15 clinically confirmed INO and 15 control subjects underwent conventional MRI at 1.5 T consisting of T2-weighted, proton density (PD)-weighted, and fluid-attenuated inversion recovery (FLAIR) sequences, following full institutional approval. A free-response, multiple-reader multiple-case design ROC study was used to evaluate the diagnostic efficacy of each sequence. All imaging sequences were evaluated by 10 board-certified neuroradiologists. Area under the curve (AUC), sensitivity, and specificity were analysed statistically for all three pulse sequences using repeated-measures analyses of variance and post-test analysis using Bonferroni's multiple comparison test of differences. RESULTS: No significant AUC differences were found between the three sequences (p = 0.0697), with T2 recording the highest AUC (0.8346). Sensitivity differences between PD (0.7927) and FLAIR (0.6329) were significant (p < 0.05). Non-significant differences were also evident between T2 and FLAIR (p = 0.0511). The specificity analysis revealed an overall difference (p = 0.0005), with specific inter-sequence differences shown between T2 and PD (p < 0.05) and PD and FLAIR (p < 0.001) with the PD values being lower than those provided with the other two sequences. CONCLUSION: T2-weighted axial imaging through the MLF region resulted in the greatest overall diagnostic efficacy when viewing a combination of mean AUC, sensitivity, and specificity, in terms of the identification of INO-causing lesions.

Immunomodulators for multiple sclerosis may ameliorate spinal bone loss.

BACKGROUND: The effect of immunomodulator therapy (IMT) for multiple sclerosis (MS) on bone turnover is unknown. AIM: The aim of this study was to assess bone turnover in MS patients on IMT. METHODS: MS patients (n = 29) on maintenance IMT had repeat measurement of bone mineral density (BMD) after a 4.0 ± 0.4 years; bone turnover markers (BTM) were measured at the time of repeat BMD. RESULTS: BMD was unchanged at the spine but declined at the hip. BTMs, both resorption and formation, were reduced compared to normative range that may indicate an anti-resorptive action of IMT. Significant negative correlations were noted between BTMs and changes in BMD at spine but not hip. CONCLUSION: These observations suggest that IMT may have a beneficial effect on spinal bone by an antiresorptive action. A prospective study of the effect of IMT on BMD and bone turnover is warranted.

Change in PASAT performance correlates with change in P3 ERP amplitude over a 12-month period in multiple sclerosis patients.

OBJECTIVE: To examine the correlation between the change in PASAT and the change in P3 event-related potentials (ERPs) over a 12-month period in multiple sclerosis (MS) patients, and to compare the 12-month change in the P3 ERP between MS patients and controls. METHODS: Forty-four subjects (27 MS patients, 17 controls) completed visual and auditory two-stimulus oddball and three-stimulus oddball tasks at Month 0 and Month 12. Data were recorded from a 128-scalp channel electroencephalography array. Data from scalp channels were converted into continuous interpolated images (incorporating the entire scalp and time). Amplitude, topographical differences and correlations were then tested using statistical parametric mapping. RESULTS: The change in visual and auditory P3a correlated significantly with the change in PASAT score (r=0.56, p<0.001 and r=0.48, p=0.003, respectively). Visual P3b and P3a showed greater decrease in 12 months in MS patients relative to controls. Visual P3b, auditory P3b and auditory P3a amplitudes had significantly decreased in MS patients after 12-month period. CONCLUSIONS: Change in visual and auditory P3a ERP amplitudes correlate with change in PASAT scores in MS patients. Visual modality is more sensitive to changes in P3 ERP amplitudes over 12-month period. SIGNIFICANCE: P3 ERPs may have utility in monitoring the change in cognitive functioning in MS.

Multiple sclerosis prevalence in Ireland: relationship to vitamin D status and HLA genotype.

BACKGROUND: The relationship between prevalence of multiple sclerosis (MS) and latitude may be due to both genetic and environmental factors. The hypothesis that, in Ireland, MS prevalence is increasing and that north-south differences relate to variation in serum 25-hydroxyvitamin D (25(OH)D) levels was tested in this study. PATIENTS AND METHODS: Patients and matched control subjects were identified in counties Donegal, Wexford and South Dublin through multiple sources. Prevalence was determined. Blood samples were taken for serum 25(OH)D and serum intact parathyroid hormone measurement, and DNA was extracted. RESULTS: Prevalence in 2007 was significantly greater in Donegal (northwest) (290.3/105, 95% CI 262.3 to 321.7) compared with 2001 (184.6/105; 162 to 209.5). In Wexford (southeast), there was a non-significant increase in prevalence in 2007 compared with 2001. Prevalence was significantly higher in Donegal than in Wexford (144.8/105; 126.7 to 167.8, p<0.0001) and South Dublin (127.8/105; 111.3 to 148.2, p<0.0001). Overall, mean 25(OH)D levels were low and did not differ between patients (38.6 nmol/l) and controls (36.4 nmol/l) However, significantly more patients than controls had 25(OH)D levels <25 nmol/l (deficiency) (p=0.004). Levels of 25(OH)D (mean 50.74 nmol/l) were significantly higher in South Dublin (area with lowest prevalence) (p<0.0001) than in Donegal or Wexford. HLA DRB1*15 occurred most frequently in Donegal (greatest MS prevalence) and least frequently in South Dublin. CONCLUSION: Vitamin D deficiency is common in Ireland. Latitudinal variation in MS probably relates to an interaction between genetic factors and environment (25(OH)D levels), and MS risk may be modified by vitamin D in genetically susceptible individuals.

Preliminary evidence for correlation between PASAT performance and P3a and P3b amplitudes in progressive multiple sclerosis.

BACKGROUND: The no-go P3a event-related potential (ERP) is a measure of attentional engagement and the P3b is a measure of context updating. The aim of this study was to compare ERP topographies: (i) to Paced Auditory Serial Addition Test (PASAT) results, (ii) of visual and auditory P3a and P3b of patients with primary progressive multiple sclerosis (PPMS) versus patients with secondary-progressive multiple sclerosis (SPMS) and (iii) of both progressive subtypes to healthy controls. METHODS: Thirty subjects (10 PPMS, 10 SPMS and 10 age-matched controls) completed visual and auditory no-go P3a and P3b tasks whilst data were recorded from a 128-scalp channel electroencephalography (EEG) array. Data from scalp channels were converted into continuous interpolated images (incorporating the entire scalp and time). Topographical differences and correlations were then tested using statistical parametric mapping. RESULTS: For the patients with multiple sclerosis (MS), PASAT score correlated significantly with parietal regions in the auditory P3b, auditory P3a and visual P3b conditions, and with central regions in the visual P3a condition. Patients with PPMS had significantly lower amplitude than patients with SPMS in the auditory P3b condition over the parietal area. The control group had greater amplitude than the patients with MS in all the P3 tasks, with the exception of the auditory P3b. CONCLUSIONS: These data suggest that PASAT performance and P3 ERPs correlate for MS progressive subtypes and that PPMS and SPMS differ in electrophysiological responses during auditory P3b tasks.

OAS1: a multiple sclerosis susceptibility gene that influences disease severity.

BACKGROUND: Type 1 interferons upregulate oligoadenylate synthetase 1 (OAS1). A single nucleotide polymorphism (SNP) in exon 7 of OAS1 results in differential RNAseL enzyme activity, the A allele coding for a truncated form with low activity and the G conferring high activity. We hypothesized that OAS1 genotypes would influence both susceptibility to multiple sclerosis (MS) and disease activity with the AA genotype being overrepresented and the GG genotype underrepresented in relapsing-remitting MS (RRMS) with increased disease activity. METHODS: We examined OAS1 genotype distribution in 401 patients with MS, 394 healthy controls, and 178 patients with RRMS receiving interferon-beta (IFNbeta) assessed as 1) having no or minimal disease activity on IFNbeta, 2) having disease activity despite IFNbeta, and 3) 65 patients with RRMS with highly active disease. RESULTS: The OAS1 genotype distribution differed between patients with MS and controls (p = 0.000003), with lower frequency of GG homozygotes in patients with MS (6%) compared with controls (17%). In relation to disease severity, 34 (32%) patients with no or minimal disease activity on IFNbeta had the AA and 8 (8%) the GG genotype; of patients with disease activity despite IFNbeta, 27 (51%) were AA, while only 1 (2%) was GG (p = 0.03). Median time to first relapse on IFNbeta was 24 months in patients with RRMS with AA genotype and 33 months with AG or GG genotype (p = 0.04). The GG genotype was absent in 65 patients with highly active RRMS (p = 0.03). CONCLUSIONS: A functional OAS1 SNP, AA genotype, confers susceptibility to MS and the GG genotype may protect against increased disease activity.

Impaired information processing speed and attention allocation in multiple sclerosis patients versus controls: a high-density EEG study.

BACKGROUND: The no-go P3a is a variant of the P300 event-related potential (ERP) that indexes speed of information processing and attention allocation. The aim of this study was to compare ERP findings with results from the paced auditory serial addition test (PASAT) and to quantify latency, amplitude and topographical differences in P3a ERP components between multiple sclerosis (MS) patients and controls. PATIENTS AND METHODS: Seventy-four subjects (20 relapsing remitting (RRMS) patients, 20 secondary progressive (SPMS) patients and 34 controls) completed a three-stimulus oddball paradigm (target, standard, and non-target). Subjects participated in separate visual and auditory tasks while data were recorded from 134 EEG channels. Latency differences were tested using an ANCOVA. Topographical differences were tested using statistical parametric mapping. RESULTS: Visual P3a amplitude correlated with PASAT score in all MS patients over frontal and parietal areas. There were significant differences in latency, amplitude, and topography between MS patients and controls in the visual condition. RRMS and SPMS patients differed in visual P3a latency and amplitude at frontal and parietal scalp regions. In the auditory condition, there were latency differences between MS patients and controls only over the parietal region. CONCLUSION: The present results demonstrate that information processing speed and attention allocation are impaired in MS.

A high-density ERP study reveals latency, amplitude, and topographical differences in multiple sclerosis patients versus controls.

OBJECTIVE: To quantify latency, amplitude and topographical differences in event-related potential (ERP) components between multiple sclerosis (MS) patients and controls and to compare ERP findings with results from the paced auditory serial addition test (PASAT). METHODS: Fifty-four subjects (17 relapsing remitting (RRMS) patients, 16 secondary progressive (SPMS) patients, and 21 controls) completed visual and auditory oddball tasks while data were recorded from 134 EEG channels. Latency and amplitude differences, calculated using composite mean amplitude measures, were tested using an ANOVA. Topographical differences were tested using statistical parametric mapping (SPM). RESULTS: In the visual modality, P2, P3 amplitudes and N2 latency were significantly different across groups. In the auditory modality, P2, N2, and P3 latencies and N1 amplitude were significantly different across groups. There were no significant differences between RRMS and SPMS patients on any ERP component. There were topographical differences between MS patients and controls for both early and late components for the visual modality, but only in the early components for the auditory modality. PASAT score correlated significantly with auditory P3 latency for MS patients. CONCLUSIONS: There were significant ERP differences between MS patients and controls. SIGNIFICANCE: The present study indicated that both early sensory and later cognitive ERP components are impaired in MS patients relative to controls.

CT guided aspiration of a cervical spinal epidural abscess.

The management of spinal epidural abscess has changed over the last few years. Originally treatment was thought to be urgent surgical evacuation. In the more recent literature less invasive techniques have been suggested. We present a case, where a cervical epidural abscess at the C2 level was treated with CT guided aspiration and antibiotic therapy. This has not been previously reported.

Sleep apnea in obese miniature pigs.

We postulated that three extremely obese Yucatan miniature pigs would have more sleep apnea than three nonobese Yucatan miniature pigs. Pigs were studied with the use of electroencephalograms, inductance plethysmography, oximetry, expired nasal CO2, or thermistors. All of the obese pigs, but none of the nonobese pigs, had both sleep apnea (8.5, 10.3, and 97.0 in obese pigs vs. O apnea + hypopnea/h in all nonobese pigs; P < 0.05) and oxyhemoglobin desaturation episodes during sleep [9.4 +/- 3.0 vs. 0 + 0.53 (SD) mean desaturation episodes/h in obese pigs vs. nonobese pigs, respectively; P < 0.05]. Two of the extremely obese pigs had obstructive sleep apnea, whereas the third obese pig had central sleep apnea. We conclude that sleep apnea occurs in extremely obese Yucatan minipigs and suggest that this animal can be used as a model for sleep apnea in obesity.

Tips of the trade. Detecting patellar surface irregularities.

A method of determining the presence of patellar surface irregularity, which the author calls the megaphone test, is described. By forming a simple echo chamber with the hand, crepitant sounds created by patellar roughening can be detected. This test, however, does not quantify or determine the cause of the crepitus.

The percutaneous lateral retinacular release.

This study reviews 34 of 37 original patients who were reviewed in 1981 after previously undergoing percutaneous lateral retinacular release. Short-term satisfactory results regarding reduction of pain and prevention of dislocation were maintained on this second followup (average, 48 months). With this increase in postoperative time, patients with recurrent subluxation developed an increase in patellar slipping. Patients with chondromalacia and degenerative joint disease are less suited for long-term treatment. Long-term problems occurred in 1 of 34 patients (3%).

Kinetic sources of lower-limb angular displacement in the recovery phase of sprinting.

One female sprinter was filmed at the 100-m mark (speed 6.5 m X S-1) of a 400-m run. Four moments occurring at each end of the thigh and shank segments during lower-limb recovery were calculated. These were: proximal and distal net muscle moments, a moment due to proximal joint accelerative force and, a moment due to distal joint-force resulting from motion and inertia of the distal connected segment. Individual contributions of each moment to segmental angular displacement were calculated by double integration, and angular velocity at toe-off was multiplied by time to yield its contribution. Contributions of the proximal muscle moments throughout recovery were 21 rad and 7.5 rad for the thigh and shank segments, respectively. Such large angular displacements did not occur because the three remaining moments opposed the proximal muscle moment. These large moments are mutually offsetting and interactive, acceleration of proximal joints provides a substantial moment during contralateral stance, and segmental angular velocity at toe-off is a significant contributor. Consequently, a phenomenon producing a change in any moment (e.g. muscular fatigue, slippery surface) will require modification of other moments for angular displacement to be maintained within reasonable limits.

Arthroscopic surgery for relief of pain in the osteoarthritic knee.

This retrospective study reviews 43 patients with osteoarthritis of the knee who underwent arthroscopic surgery, from January 1979 until April 1982. Percutaneous drilling of an osteochondral defect in the femoral condyle was performed in 22 patients to relieve the high intraosseous pressure and rest pain associated with this disease; successful results were recorded in 80% of patients at an average followup of 25.1 months. Partial meniscectomy was performed in 21 patients to remove an obstructing degenerative meniscal tear; 81% had successful results with an average followup of 40.6 months. There were no postoperative complications. Percutaneous drilling and excision of degenerative meniscal tears can be valuable arthroscopic procedures in properly selected patients with osteoarthritis of the knee.

The percutaneous lateral retinacular release.

A lateral retinacular release performed through a 2 ½-3 cm lateral parapatella incision can give rewarding results for patients with chondromalacia, degenerative joint disease, recurrent subluxation or recurrent dislocation of the patella. A retrospective review from August 1978 to December 1980 of 37 patients (42 knees) shows 83% excellent or satisfactory results, 17% unsatisfactory results with an average postoperative follow-up of 12.3 months. Preoperative pain was reduced in all but two patients; no patient was made worse by the procedure with respect to pain or function. In 17 knees with recurrent dislocation of the patella there were no recurrences of dislocation. Patients having Class IV chondromalacia, considered degenerative joint disease of the patellofemoral joint, and those patients over 35 years of age had the poorest results. One hemarthrosis was the only immediate postoperative complication. Four patellectomies and one recurrent medial subluxation were the long-term failures. Comparison with the results of other treatment methods - including patella shaving, patella curettage and drilling, patellectomy, patellar prosthesis, and realignment procedures- shows the results of the percutaneous lateral retinacular release to compare favorably within the limitations of short-term follow-up.