Detection Of Multiple Sclerosis Research Articles

OCT and OCT-A biomarkers in multiple sclerosis - review.

Objective: Retinal neuronal and vascular changes have been observed in multiple sclerosis (MS) patients. The aim of this review was to highlight the most current optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) data in MS and to provide information about the possibility of using OCT / OCT-A parameters as biomarkers for screening, diagnosis and monitoring of MS. Methods: To carry out this review, a meticulous literature search was undergone on PubMed between 2014 and the present day, using the following terms: "multiple", "sclerosis", "optical", "coherence", "tomography" and "angiography". Additional studies were found via references, being chosen according to relevance. Results: Retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) were significantly lower in MS patients compared to controls, and correlated with clinical and paraclinical variables, such as visual function, disability, and magnetic resonance imaging (MRI). Retinal capillary plexuses could be higher, lower or the same, and the best OCT-A microvasculature parameter for the detection of MS was the superficial capillary plexus (SCP). The reduced retinal vessel density (VD) was correlated with the disability in MS. Conclusions: OCT and OCT-A parameters could improve the development of retinal biomarkers for screening, early diagnosis and monitoring the disease progression of MS, and they could improve the development of potential future therapies that could slow or stop the course of this incurable disease. Abbreviations: DCP = deep capillary plexus; EDSS = Expanded Disability Status Scale; GCC = ganglion cell complex; GCL = ganglion cell layer; MRI = magnetic resonance imaging; MS = Multiple sclerosis; OCT = optical coherence tomography; OCT-A = optical coherence tomography angiography; ON = optic neuritis; RNFL = retinal nerve fiber layer; SCP = superficial capillary plexus; VD = vessel density.

Graph-Based Analysis of Brain Connectivity in Multiple Sclerosis Using Functional MRI: A Systematic Review.

(1) Background: Multiple sclerosis (MS) is an immune system disease in which myelin in the nervous system is affected. This abnormal immune system mechanism causes physical disabilities and cognitive impairment. Functional magnetic resonance imaging (fMRI) is a common neuroimaging technique used in studying MS. Computational methods have recently been applied for disease detection, notably graph theory, which helps researchers understand the entire brain network and functional connectivity. (2) Methods: Relevant databases were searched to identify articles published since 2000 that applied graph theory to study functional brain connectivity in patients with MS based on fMRI. (3) Results: A total of 24 articles were included in the review. In recent years, the application of graph theory in the MS field received increased attention from computational scientists. The graph-theoretical approach was frequently combined with fMRI in studies of functional brain connectivity in MS. Lower EDSSs of MS stage were the criteria for most of the studies (4) Conclusions: This review provides insights into the role of graph theory as a computational method for studying functional brain connectivity in MS. Graph theory is useful in the detection and prediction of MS and can play a significant role in identifying cognitive impairment associated with MS.

Development of an Electrochemical CCL5 Chemokine Immunoplatform for Rapid Diagnosis of Multiple Sclerosis

Serum level of CCL5 chemokine is considered an emerging biomarker for multiple sclerosis (MS). Due to the lack of specific assays for this disease, the development of a point-of-care test for rapid detection of MS could lead to avoiding diagnostics delays. In this paper, we report the first electrochemical immunoplatform for quantification of the CCL5 biomarker at the clinically required levels, able to discriminate between patients diagnosed with MS and healthy individuals. The immunosensing device involves protein capture from biological samples by complexation with biotinylated specific antibodies immobilized onto neutravidin-functionalized microparticles and sandwich assay with anti-CCL5 antibody and IgG labelled with horseradish peroxidase (HRP) for the enzyme-catalyzed amperometric detection of H2O2 using hydroquinone (HQ) as the redox mediator. The method shows excellent analytical performance for clinical application with a wide linear range of concentrations (0.1–300 ng·mL−1 CCL5, R2 = 0.998) and a low detection limit (40 pg·mL−1 CCL5). The biosensing platform was applied to the determination of the CCL5 endogenous content in 100-fold diluted sera both from healthy individuals and patients diagnosed with MS, with no further sample treatment in just two hours. The results were successfully compared with those obtained by the ELISA methodology.

Multiple sclerosis in the otoneurology outpatient clinic: interdisciplinary cooperation between otoneurologist and neurologist

Summary Introduction: Multiple sclerosis (MS) is a chronic multifocal inflammatory disease affecting the CNS, with autoimmune and neurodegenerative processes involved in its pathogenesis. Otoneurology outpatient clinic patients presenting with hearing loss, tinnitus, and vertigo may eventually be newly dia­gnosed MS patients. An otoneurologist specialist may be the first physician to suspect MS and refer the patient for an MRI and neurological examination. Early dia­gnosis and subsequent treatment of MS can delay permanent disability. Aim: Analysis of the incidence of MS patients in an otoneurological outpatient clinic during a twenty-year period. To increase the otoneurologists’ awareness of MS dia­gnosis. Methods and materials: Of 6,000 patients, who were newly examined in an otoneurology outpatient clinic between 2000 and 2021, data of 11 patients (0,18%) (5 male/6 female, aged 25–58 years) with MS or suspected of MS were retrospectively evaluated. Results: In 11 patients, MS was suspected or ongoing. In 4 of those patients, otoneurological examination contributed to the first detection of MS by an otoneurologist. The first MS symptoms included hearing loss, tinnitus, instability, and post-infection visual disorder. Conclusion: The otoneurologist must consider that sudden hearing loss, tinnitus, and vertigo may be the first manifestations of MS. Early dia­gnosis of MS increases the likelihood that with treatment, the progression of the disease will be slowed. Interdisciplinary cooperation between the otoneurologists and neurologists is very important for the dia­gnosis of MS. Key words multiple sclerosis – sensorineural hearing loss – tinnitus – vertigo – otoneurology

Multiple Sclerosis: A Neurological Disorder

Multiple sclerosis (MS)is a long lasting, chronic and auto-immune disease which affects central nervous system. In this auto-immune disease, our own immune system damages the body.It is a disabling disease of spinal cord and brain, specially deteriorates optic nerve of eyes. The disease is caused when immune system of the body attacks on myelin sheath which is a protective layer of neurons; the structural and functional unit of nervous system. This sheath protects the nerve fibers. Damage to myelin sheath exposes the nerve fibers, which slows down or blocks the nerve impulse passing through the nerve. This disease appears between the ageof 20 to 50 years in most cases. Statistics reveal that it is more common in women than men. The causes of this disease are unknown but scientists believe that the risk factor of this disease is the combination of genetics and environment. Its symptoms include effects on body movements involving loss of balance, weakness or numbness in limbs, dizziness, body pains, electric shock sensations specially in neck region,fatigue,difficulty swallowing, slurred speechand vertigo.It also involves problems relating sexual, bowel and bladder functions. It may also cause depression and anxiety.The symptoms are different in children than adults. It starts with acute encephalomyelitis, including fever, stiff neck, seizures, coma and confusion. It these symptoms persist, doctor should be consulted immediately.
 Research has shown that there are some factors whichcan increase the chances of its development. These factors include;age,climate, Vitamin D and other auto-immune diseases. MS can occur at any age in one’s life but its onset is common between 20 to 50 years. The risk of developing of MS in twin babies is 1 in 4 cases. However, younger and older people can be affected too.Considering the factor of climate, MS is found to be more common in countries found in temperate regions of the world. Statistics have shown that MS was common in people living in New Zealand, Canada, USA and many other European countries. All of us know what is the importance of vitamins. It has been observed that lower levels of Vitamin D and decreased sunlight exposure are related with greater risk of this disease. Many people suffer from auto-immune diseases for example pernicious anemia, Inflammatory bowel disease, Type I Diabetes Mellitus and thyroid problems. Recent studies show that person already facing the trouble of auto-immune disease is at higher risk of getting MS. Multiple sclerosis (MS) has been divided into four basic types: Primary progressive MS (PPMS), Secondary Progressive MS (SPMS), Progressive Relapsing MS (PRMS) and Relapsing Remitting MS (RRMS).
 Recent findings from a National MS Society estimated that nearly 1 million people in the United States are affected with MS. This is more than double the last reported number, and the first national research on MS prevalence since 1975. The society also estimated that 2.3 million people live with MS globally.
 There is no specific laboratory or diagnostic test to check for MS. For detection of MS, differential diagnosis is used in which signs, symptoms and patients condition is used to rule out the overall scenario. Some blood tests are recommended by doctors which check specific biomarkers associated with MS. MRIis helpfuland it can reveal some areas of spinal cord and brain to see lesions.Spinal tap in which a small sample of cerebrospinal fluid is removed from the spinal canal for laboratory analysis. This sample can show abnormalities in antibodies that are associated with MS.Electric signals produced by nervous system in response to specific stimuli are recorded in a test called Evoked potential test. It’s unfortunate that there is no complete cure of this disease up-till now. Treatment helps tospeed up the, slowing the progression of the disease and managing MS symptoms to help patient live a better life. Treatment for attacks includes the useof corticosteroids and plasma exchange.
 Previously, it was thought that this disease is uncommon in Pakistan. But new data shows its prevalence to be 10 in 10,0000 of population. It is affecting the Pakistani population on same patterns as found in West. It is found to be more common in women than men. It has been affecting more people who are passing third decade of life. Among its types, Relapsing-Remitting MS (RRMS) is more common in Pakistan. It’s unfortunate that the reports about this disease are few in numbers and there is a need to conduct a thorough research in hope of finding a complete cure of this disease and making the life of patients affected by it much more comfortable.

Platelets in Multiple Sclerosis: Early and Central Mediators of Inflammation and Neurodegeneration and Attractive Targets for Molecular Imaging and Site-Directed Therapy.

Platelets are clearly central to thrombosis and hemostasis. In addition, more recently, evidence has emerged for non-hemostatic roles of platelets including inflammatory and immune reactions/responses. Platelets express immunologically relevant ligands and receptors, demonstrate adhesive interactions with endothelial cells, monocytes and neutrophils, and toll-like receptor (TLR) mediated responses. These properties make platelets central to innate and adaptive immunity and potential candidate key mediators of autoimmune disorders. Multiple sclerosis (MS) is the most common chronic autoimmune central nervous system (CNS) disease. An association between platelets and MS was first indicated by the increased adhesion of platelets to endothelial cells. This was followed by reports identifying structural and functional changes of platelets, their chronic activation in the peripheral blood of MS patients, platelet presence in MS lesions and the more recent revelation that these structural and functional abnormalities are associated with all MS forms and stages. Investigations based on the murine experimental autoimmune encephalomyelitis (EAE) MS model first revealed a contribution to EAE pathogenesis by exacerbation of CNS inflammation and an early role for platelets in EAE development via platelet-neuron and platelet-astrocyte associations, through sialated gangliosides in lipid rafts. Our own studies refined and extended these findings by identifying the critical timing of platelet accumulation in pre-clinical EAE and establishing an initiating and central rather than merely exacerbating role for platelets in disease development. Furthermore, we demonstrated platelet-neuron associations in EAE, coincident with behavioral changes, but preceding the earliest detectable autoreactive T cell accumulation. In combination, these findings establish a new paradigm by asserting that platelets play a neurodegenerative as well as a neuroinflammatory role in MS and therefore, that these two pathological processes are causally linked. This review will discuss the implications of these findings for our understanding of MS, for future applications for imaging toward early detection of MS, and for novel strategies for platelet-targeted treatment of MS.

New possibilities of siponimod therapy in patients with secondary progressive multiple sclerosis

The process of neurodegeneration in multiple sclerosis (MS) remains an urgent problem of modern neurology; from the point of view of its therapy, it is especially important to identify this condition during the transition to secondary progression. This paper reflects the opinion of the Council of Leading MS Experts on the early detection of secondary progressive MS and its diagnostic tools, including the use of new online questionnaires. Special attention is paid to the concept of clinical progression verification using the indicator of the confirmed progression of disability and to the prospect for introducing siponimod (Kiendra® ) into clinical practice for the treatment of patients with secondary progressive MS.

Should We Use Clinical Tools to Identify Disease Progression?

The presence of disability progression in multiple sclerosis (MS) is an important hallmark for MS patients in the course of their disease. The transition from relapsing remitting (RRMS) to secondary progressive forms of the disease (SPMS) represents a significant change in their quality of life and perception of the disease. It could also be a therapeutic key for opportunities, where approaches different from those in the initial phases of the disease can be adopted. The characterization of structural biomarkers (e.g., magnetic resonance imaging or neurofilament light chain) has been proposed to differentiate between both phenotypes. However, there is no definite threshold between them. Whether the risk of clinical progression can be predicted by structural markers at early disease phases is still a focus of clinical research. However, several theories and pathological evidence suggest that both disease phenotypes are part of a continuum with common pathophysiological mechanisms. In this case, the clinical evaluation of the patients would play a preponderant role above destruction biomarkers for the early identification of disability progression and SPMS. For this purpose, the use of clinical tools beyond the Expanded Disability Status Scale (EDSS) should be considered. Besides established functional tests such as the Multiple Sclerosis Functional Composite (MSFC), patient's neurological history or digital resources may help neurologists in the decision-taking. In this article, we discuss arguments for the use of clinical markers in the detection of secondary progressive MS and the characterization of progressive disease activity.

Automatic detection of multiple sclerosis lesions using Mask R‐CNN on magnetic resonance scans

Multiple Sclerosis (MS) causes the central nervous system to malfunction due to inflammation surrounding nerve cells. Detection of MS at an early stage is very important to prevent progressive MS attacks. Clinical findings, cerebrospinal fluid examinations, the evoked potentials, magnetic resonance imaging (MRI) findings have an important role in the diagnosis and follow-up of MS. However, many of the findings on MRI may indicate brain disorders other than MS. In addition, the clinical practices accepted by physicians for MS detection are very limited. In this study, a Mask R-CNN based method in two dataset is proposed for the automatic detection of MS lesions on magnetic resonance scans. We also improved the ROI detection stage with RPN in the Mask R-CNN to easily adapt for different lesion sizes. MS lesions in different sizes in the dataset are successfully detected with 84.90% Dice similarity rate and 87.03% precision rates using the proposed method. In addition, volumetric overlap error and lesion-wise true positive rate are obtained as 12.97% and 73.75%, respectively. Moreover, performance tests of the use of different numbers of GPU hardware structures are also performed and the evaluation of its effects on processing speed is performed on experimental studies..

Detection of multiple sclerosis using blood and brain cells transcript profiles: Insights from comprehensive bioinformatics approach

Abstract Multiple sclerosis (MS) is a severely disabling disease affecting the brain and spinal cord. The detection of MS at an early stage is difficult. However, detection of MS from blood cell gene expression may ameliorate the early identification of MS. The present study addressed overlapped genes between blood cell and brain tissues of MS patients. We analyzed microarray gene expression brain tissue datasets and eQTL data to identify overlapped genes in the blood and brain of MS patients. We identified 23 overlapped differentially expressed genes (DEGs) (PWP2, UPK3BL, NFATC3, NPIPA5, KNOP1, PIK3C2B, LDLRAP1, HN1L, FAM226B, STAG3L2, ZNF814, BMS1P5, SDCCAG8, CLN8, ARHGEF7, NEAT1, ANKRD42, C5orf34, DOK6, PKN2, SP1, DBF4B, VAMP3) in the blood cells and brain tissues of MS patients. The axon guidance mediated and postsynaptic differentiation associated pathways were enriched by the DEGs. The significant regulatory transcription factors (TFs) including SP1, ARNT, MEF2A, YY1, EGR1, MIF, FOS, NFYA, TFAP2A, MYC, USF, MXI1, JUN, MAX, E2F1, POU3F2, GABPA, TFAP2C, CUX1, 2623, SPI1 and microRNAs (miRNAs) including miR-650, miR-223, miR-9, miR-181b, miR-190, miR-561, miR-520c-3p, miR-658, miR-199b-5p, miR-660, miR-20 were identified in MS. The candidate drugs were determined from drug target overrepresentation analysis. This study provides biomarkers at protein levels (hub proteins and TFs) and RNA levels (mRNAs, miRNAs) in MS subjects that were similarly dysregulated in both blood and brain tissues.

A Nanobiosensor Based on Fluorescent DNA-Hosted Silver Nanocluster and HCR Amplification for Detection of MicroRNA Involved in Progression of Multiple Sclerosis.

MicroRNAs (miRNA) are a novel class of small noncoding RNAs with roles in RNA silencing and post transcriptional regulation of gene expression. Due to their roles, miRNA can be considered as new biomarkers for prognosis of diseases such as Multiple sclerosis (MS). Herein, we report a miRNA nanobiosensor based on nucleic acid hybridization chain reaction and highly fluorescent DNA hosted silver nanoclusters (NC). In our method, two types of hairpin oligonucleotide probes, MB1 and MB2, were employed as hybridization chain reaction (HCR) monomers, where MB1 acted as a template for in situ synthesis of fluorescent Ag NC. These monomers were stable in solution but they triggered a cascade of hybridization events once miR-145 (a biomarker of MS in blood) was added to the solution. The process yielded nicked double stranded DNA. The nanobiosensor showed great sensitivity for the detection of target microRNA and excellent limit of detection of about 0.1nM with high specificity to differentiate sharply between complementary, mismatch, and non-complementary target miRNAs. Alongside the outstanding sensitivity and selectivity, the nanobiosensor exhibited great reproducibility, stability and a decent response in real sample analysis with blood plasma. In conclusion, this simple and highly responsive nanobiosensor can clinically be used for the early detection of MS by direct detection of the plasma miR-145 in real clinical samples, without a need for sample preparation, RNA extraction and/or amplification.

Assessment of the diagnostic accuracy of double inversion recovery sequence compared with FLAIR and T2W_TSE in detection of cerebral multiple sclerosis lesions.

BackgroundMultiple sclerosis (MS) is a demyelinating disease of the central nervous system. MRI has an important role in early diagnosis of MS within diagnostic criteria.AimTo determine the diagnostic value of the double inversion recovery (DIR) sequence in detection of brain MS lesions.MethodsIn this cross-sectional study, 55 patients were admitted to the MRI department in Vali-E-Asr Hospital in Qaemshahr, Iran, from May 2016 to February 2016. Imaging was performed on a 1.5T Philips MR system using DIR, fluid attenuated inversion recovery (FLAIR), and T2-weighted turbo spin echo (T2W_TSE) sequences with the same parameters, including field of view (FOV), matrix, slice thickness, voxel size, and number of signal averaging (NSA). The DIR sequence has two different time inversions (TI1=3400, TI2=325ms): suppressing cerebrospinal fluid (CSF) and white matter signal. Data analysis was performed using the SPSS version 20, and p-value was gained from the patient-wise analysis by Wilcoxon analysis and paired samples t-test for matched pairs.ResultsMore lesions in number and size were depicted on the DIR sequence compared with FLAIR (p=0.000 with a relative ratio of 6) and T2W_TSE (p=0.000 with a relative ratio of 10). DIR demonstrated significantly more intracortical lesions compared with FLAIR (p=0.000 with a relative ratio of 2.53) and T2W_TSE (p=0.000 and relative ratio of 8.87). There was significantly higher contrast ratio between the white matter lesions and the normal appearing white matter (NAWM) in all anatomical regions especially in deep white matter (p=0.001).ConclusionAn increasing total number of MS lesions can be detected by DIR sequence; thus, we recommend adding DIR sequence in routine MR protocols for MS patients.

Segmentation of multiple sclerosis lesions in MR images: a review

Multiple sclerosis (MS) is an inflammatory demyelinating disease that the parts of the nervous system through the lesions generated in the white matter of the brain. It brings about disabilities in different organs of the body such as eyes and muscles. Early detection of MS and estimation of its progression are critical for optimal treatment of the disease. For diagnosis and treatment evaluation of MS lesions, they may be detected and segmented in Magnetic Resonance Imaging (MRI) scans of the brain. However, due to the large amount of MRI data to be analyzed, manual segmentation of the lesions by clinical experts translates into a very cumbersome and time consuming task. In addition, manual segmentation is subjective and prone to human errors. Several groups have developed computerized methods to detect and segment MS lesions. These methods are not categorized and compared in the past. This paper reviews and compares various MS lesion segmentation methods proposed in recent years. It covers conventional methods like multilevel thresholding and region growing, as well as more recent Bayesian methods that require parameter estimation algorithms. It also covers parameter estimation methods like expectation maximization and adaptive mixture model which are among unsupervised techniques as well as kNN and Parzen window methods that are among supervised techniques. Integration of knowledge-based methods such as atlas-based approaches with Bayesian methods increases segmentation accuracy. In addition, employing intelligent classifiers like Fuzzy C-Means, Fuzzy Inference Systems, and Artificial Neural Networks reduces misclassified voxels.

Expression of leukemia inhibitory factor in the cerebrospinal fluid of patients with multiple sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, characterized by infiltration of immune cells in the central nervous system, localized myelin destruction and loss of oligodendrocytes. Early detection of MS may be possible via blood and cerebrospinal fluid (CSF) tests based on disease pathology. Leukemia inhibitory factor (LIF), a neurotrophic cytokine, has previously been shown to limit autoimmune demyelination and oligodendrocyte loss in a murine model of MS. Given its potential role in neural cell death and survival, in the present study we measured expression of LIF in serum and CSF from patients with relapsing-remitting MS ( n = 46) and control subjects ( n = 42). We used western blot analysis and enzyme-linked immunosorbent assays (ELISA), to study LIF expression. Western blot analysis revealed that LIF was present in all CSF samples, and densitometric analysis showed that relative expression was significantly higher in CSF from patients with MS than in controls ( p < 0.001). ELISA analysis showed that the concentrations of LIF in both the serum (87.5 ± 11.46 ng/mL) and CSF (56 ± 10.72 ng/mL) of MS patients were significantly higher than those in control subjects (52 ± 8.23 ng/mL, 7.8 ± 3.76 ng/mL, respectively; p < 0.0001 for both serum and CSF), despite there being no significant difference in total protein concentration between the two groups ( p = 0.52 for serum, p = 0.2 for CSF). Our data suggest that serum and CSF concentrations of LIF may provide additional useful information during the differential diagnosis of MS. Our findings also indicate that LIF could be significantly involved in the pathophysiology of MS.

Letters to the Editor

Letters to the Editor

Active MS plaques: efficiency of contrast-enhanced magnetization transfer subtraction technique

T1-weighted (T1W) magnetic resonance images with magnetization transfer (MT) are widely used in the evaluation of multiple sclerosis (MS) plaques. We aimed to evaluate the contribution of the subtraction technique with MT in the detection of acute MS plaques. Sixty-four patients during an MS attack were enrolled in the study. Axial T1W spin echo (SE) with MT, axial-sagittal T2W fast SE, axial FLAIR and postcontrast axial T1W SE magnetic resonance imaging sequence with MT were acquired from all patients. The subtraction (postcontrast-precontrast) images were obtained on the workstation. FLAIR and T2W images were used as reference for plaque imaging. Contrast material enhanced plaques were considered as acute plaques. Qualitatively, both subtracted and contrast-enhanced with MT images were evaluated visually. Quantitatively, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. A total of 464 plaques were detected on T2W and FLAIR images. Thirty-five acute plaques were detected on both postcontrast MT and subtracted images. Additionally, 66 acute plaques were only detected on subtracted images visually. CNR and SNR values of acute MS plaques were significantly higher on subtracted MT images than on postcontrast MT images (P < 0.001). The subtraction technique seems to facilitate the detection of acute MS plaques by intensifying the visibility of poorly enhanced plaques without use of high dose contrast medium. We suggest the use of subtraction technique in routine imaging work-up of MS patients with acute attacks.

Clinical Research: Pattern Reversal Visual Evoked Potentials: Influence of age, Gender and Check Size in the Diagnosis of Multiple Sclerosis

The visual evoked potentials (VEP) of a group of 105 multiple sclerosis (MS) patients and a control group of 257 healthy subjects were analysed in order to investigate the influence of age, gender, and check size on the VEP latencies and amplitude. Check sizes of 17′, 10′, and 7′ were used. The best recordings were made by using the 10′ check size. The age-effect of the N100 latency is more complex than the linear increase of the P80 latency with age. In the first two decades the N100 latency slightly decreases, it then remains more or less stable in the period 20-60 years of age, and finally it increases after 60 years of age. For the P80/N100 amplitude in the first two decades a considerable decrease in amplitude can be seen, whilst it remains more or less stable in the years after 20. In the classification of the MS group vs. the control group the authors found the percentage correctly classified subjects to be 87.6%, when they used both the P80 latency and the P80/N100 amplitude in a discriminant analysis technique. The P80 latency is a more sensitive parameter than the N100 latency in the detection of MS for the check size of 10′. Amplitude is not of useful complementary value to latency in the detection of MS.

The diagnosis of multiple sclerosis: Contribution of non-clinical tests

A group of 89 patients in whom multiple sclerosis (MS) has been clinically diagnosed with varying degrees of certainty, and 25 patients with optic neuritis (ON), were subjected to the following electrophysiological tests: visual evoked response (VER), auditory brainstem-evoked response (ABER), somatosensory-evoked response (SSER), blink reflex and electronystagmography (ENG). All these patients also underwent computerized tomography (CT scan) and analysis of cerebrospinal fluid (CSF). A new diagnostic procedure is proposed, combining optimum detection of definite MS with optimally economical use of the above-mentioned non-clinical tests. The results for the MS patients show that definite MS can be diagnosed much more frequently (72%) if abnormal results in the above-mentioned tests are accepted as evidence of a (subclinical) CNS lesion. Application of the clinical diagnostic criteria of McAlpine yielded “definite MS” only in 27% of our patient material. Our diagnostic criteria showed evidence for MS in 36% of the patients clinically diagnosed as having ON. The test results were inconclusive as regards the possibility of the remaining ON patients developing MS in the future.