Diagnostic Testing In MS

Background And Methods
We examined the effect on health perceptions of a diagnostic workup in 172 patients with suspected Multiple Sclerosis (MS) using two questionnaires (Mishel, Rand Medical Outcome Study) and three Visual analogue scales measuring distress.

Patients were categorized into "MS," "not MS," or "still uncertain" groups.

Results
Patients with a definitive diagnosis reported a significant decrease in uncertainty (analysis of variance [ANOVA] P = .0004).

The medical outcome study showed a slightly worsened perceived current health status (ANOVA P = .02) and future health outlook (ANOVA P = .001) in the MS group compared with the other two groups.

Distress over physical symptoms decreased in all three groups and anxiety was more likely to decrease than increase even in those with MS.

Prognostic uncertainty distress decreased in the not MS group and still uncertain groups, whereas it remained unchanged in the MS group (P = .9156).

Conclusion
Significant and generally beneficial changes in patient health perceptions are seen associated with a Neurologic workup in suspected MS, irrespective of the final diagnosis.

Twenty-seven patients with mild Multiple Sclerosis were tested with the Dynamic Posturography Protocol used in the NeuroCom Equitest procedure.

The purpose of this study was to determine if the standard test procedure elicited a pattern of responses that would suggest the possibility of Multiple Sclerosis during differential diagnosis of a patient with dysequilibrium.

In addition, the patients' ability to align a light bar to vertical and horizontal was tested with the head erect and with the head tilted 45 degrees to the right and left shoulder.

There was a pattern of abnormality in the Equitest motor coordination tests. Only one patient produced normal scores in both the latency and adaptation tests.

No pattern of error was noted in the Sensory organization tests. In the Visual alignment tests, only 3 of the 27 patients tested produced values that were within normal limits for the three different head positions.

Visual alignment and the motor coordination tests are not specific for Multiple Sclerosis, but poor performance probably indicates a disruption of the integration of Visual, Vestibular, and SomatoSensory information.

Although patients with early Multiple Sclerosis and patients with purely Vestibular Disorders often have similar complaints, they have quite different profiles of abnormalities in posturography testing.

The sensitivities and predictive values of Visual, SomatoSensory Evoked Potentials, and BrainStem Auditory Evoked Response (EPs), CerebroSpinal Fluid OligoClonal Banding (CSF-OB) and Magnetic Resonance Imaging (MRI) were evaluated for the early diagnosis of Clinically Definite Multiple Sclerosis (CDMS).

Paraclinical evidence of asymptomatic Lesions allows a diagnosis of CDMS. Eighty-two patients in whom MS was suspected but diagnosis of CDMS was not possible entered the study prospectively.

Paraclinical examinations were performed at entry. Patients were examined and underwent EPs every 6 months, and MRI yearly.

After a mean follow-up of 2.9 years, 28 patients (34%) had developed CDMS (McDonald-Halliday criteria).

The initial MRI was Highly suggestive of MS in 19 of these (68%), while 27 (96%) had at least one MS-like abnormality in the initial MRI.

CSF-OB and EPs had lower sensitivities. CDMS developed during follow-up in 19 of the 36 patients (53%) who had an initial MRI highly suggestive of MS but in only 1 of the 25 who had normal MRI when first studied.

These results support previous conclusions that MRI is the most sensitive test for detecting White Matter asymptomatic lesions, and the most predictive for the diagnosis of CDMS.

Background & Methods
We performed a randomized trial of the incremental impact of high-volume contrast Computed Tomographic scan of the Brain.

Plus trimodal Evoked Potentials vs Magnetic Resonance Imaging of the Brain on Neurologists' diagnostic labeling of patients with suspected Multiple Sclerosis (MS).

Two hundred and four patients with suspected MS (Clinically Possible 59% or Probable 41%-McAlpine Criteria) were assessed by two Neurologists.

Patients were diagnostically categorized after reviewing the results of the tests presented in random order.

Results
Most of the change in diagnostic categorization occurred after presenting the first test result irrespective of result sequence (chi 2 = 0.01, P = .99).

The diagnoses became more definitive when all test results were available (P .001).

Magnetic Resonance Imaging and Evoked Potential were suggestive of MS equally frequently (chi 2 = 0.57, P = .45).

Conclusion
In suspected MS, there is no difference in diagnostic effect between Brain Magnetic Resonance image scanning and Computed Tomography plus trimodal Evoked Potentials.

In 22 patients with clinically definite Multiple Sclerosis (MS) who were without Visual symptoms and had a Visual Acuity of at least 1.0 in both eyes at the time of measurement.

The following tests were performed to detect subclinical lesions in the Visual system: Visual Evoked Potential (VEP), Contrast Sensitivity test (CS), Flight Of Colours test (FOC), Colour Vision test (Ishihara plates) (CV) and the Pupillary Light Reflex (PLR).

VEP was abnormal in 81.8%, CS in 72.7%, FOC in 36.4%, CV in 31.8%, and PLR in 52.3% of the patients.

VEP and CS together were most sensitive: combining these techniques subclinical Lesions of the Visual system were detected in 90.9% (20/22) of these asymptomatic patients.

Multiple Sclerosis is a chronic disease that begins in late adolescence or adulthood. It is highly variable in its expression and severity.

It is believed to be AutoImmune in nature. The cause is unknown; both Genetic and environmental factors have been implicated in the PathoGenesis.

MS generally presents with the acute or subacute onset of Neurologic abnormalities that may wax and wane over many years.

Diagnosis is generally made by means of observation of the clinical course in conjunction with a Neurological Examination and laboratory tests.

These tests may include Magnetic Resonance Imaging of the Head and Spine, Lumbar Puncture, and Evoked Potentials.

Treatment is based on general supportive care, the use of CorticoSteroids for relapses, and symptomatic management of ongoing problems.

The frequency of relapses can be reduced with Interferon-beta and Copolymer-1, for reduction in the frequency of relapses in Relapsing/Remitting MS.

Treatment of chronic progression is often attempted with ImmunoSuppressive agents such as CorticoSteroids, Azathioprine, and Cyclophosphamide. Use of other agents is being investigated.

The Committee of the European Concerted Action for Multiple Sclerosis (Charcot Foundation) organized five workshops to discuss CSF analytical standards in the diagnosis of Multiple Sclerosis.

This consensus report from 12 European countries summarises the results of those workshops. It is hoped that Neurologists will confer with their colleagues in clinical chemistry to arrange the best possible local practice.

The most sensitive method for the detection of OligoClonal ImmunoGlobulin Bands is IsoElectric focusing.

The same amounts of IgG in parallel CSF and Serum samples are used and OligoClonal Bands are revealed with IgG specific AntiBody staining.

All laboratories performing Isoelectric focusing should check their technique at least annually using "blind" standards for the five different CSF and Serum patterns.

Quantitative measurements of IgG production in the CNS are less sensitive than Isoelectric focusing.

The preferred method for detection of Blood-Brain Barrier Dysfunction is the Albumin quotient. The CSF Albumin or total protein concentrations are less satisfactory.

These results must be interpreted with reference to the age of the patient and the local method of determination. Cells should be counted. The normal value is no more than 4 cells/microliters.

Among evolving optional tests, measurement of the combined local synthesis of AntiBodies against Measles, Rubella, and/or Varicella Zoster could represent a significant advance if it offers higher specificity (not sensitivity) for identifying chronic rather than acute inflammation.

Other tests that may have useful correlations with clinical indices include those for OligoClonal free light chains, IgM, IgA, or Myelin Basic Protein concentrations.

MR imaging has had a significant impact on the understanding of Multiple Sclerosis.

The procedure now plays an important role in initial diagnostic workup, replacing some other radiologic and paraclinical tests and often confirming clinically suggested locations of lesions.

It also has contributed greatly to the understanding of the natural history of this disease, allowing objective assessment of disease load, detection of asymptomatic lesions (Clinically Silent MS lesions), and differentiation between acute and chronic Lesions.

MR imaging is highly sensitive to inflammation and DeMyelination caused by Multiple Sclerosis

And, although there is a long differential diagnosis for some of the MR findings, increasing experience has defined a number of relatively specific criteria for Multiple Sclerosis.

Recent advances may allow faster imaging and highly objective Lesion quantification, which will aid in therapeutic trials.

Physicians have recognized for a long time that disease categories provide minimal information about the impact of illness on patient experiences.

A diagnosis is important, because it can identify a course of treatment. However, there are considerable differences in how patients with similar diagnoses are affected.

Multiple Sclerosis, for example, may have essentially no impact on behavioral dysfunction or it could have devastating implications.

The impact of the disease on the daily life of the patient may be more important than the diagnosis of the condition. Physicians need to learn to treat the patient, not the disease. There are only two health outcomes that are of importance.

First, there is life expectancy. Second, there is function or quality of life. Biologic and physical events are mediators of these behavioral outcomes.

We are concerned about Cancer, high blood pressure, high cholesterol, and other problems because they may shorten a patient's life expectancy or make his or her life less desirable before death.

There is a growing consensus that these behavioral outcomes are central in studies of health care and medicine.

However, these outcomes, which can be obtained from standardized questionnaires, rarely are obtained in medical research and practice. A behavioral concept of health outcomes can suggest important new directions for research and practice.

We obtained steady-state Visual Evoked Potentials (VEPs) to Sinusoidal gratings alternating at 4 Hz with spatial frequencies varying from 0.5 to 8 cpd in 21 normal controls and 21 patients with Multiple Sclerosis (MS), and analyzed responses by fast Fourier transform.

Amplitude- and phase-spatial frequency functions were obtained and referred to as amplitude and phase "VisuoGrams."

We observed two types of abnormalities in the phase VisuoGrams of MS patients:
1. Abnormal responses at all spatial frequencies tested (37%), and
2. Abnormal responses only at selective spatial frequencies (52%).

Some patients had phase lag limited to low, middle, or high spatial frequencies. Steady-state and transient VEPs to 2 and 4 cpd showed a similar percent of abnormalities.

The use of more than one spatial frequency stimulus increased the diagnostic yield by 17%. Our data confirm that MS may selectively affect specific Neuronal channels within the Visual pathways.

Fast Spin Echo (FSE) sequences enable T₂-weighted MR scans to be obtained in a fraction of the time necessary for conventional SE sequences with long TR and long TE.

Comparison has been made of a FSE sequence (TR = 4000 ms, effective TE = 100 ms, 2 NEX) with the T₂-weighted SE sequence (TR = 2000 ms, TE = 90 ms, 1-2 NEX) normally used in 35 patients referred for Cranial MR.

Contrast-to-noise ratios (CNR) for Gray:White Matter and Brain:CSF on the FSE sequence compared favorably with Variable Echo (VE) sequences which take up to three times as long to acquire.

Although the conspicuity of some pathological Lesions such as Multiple Sclerosis plaques was inferior to that of conventional T₂-weighted SE scans, no lesions were missed on FSE scans.

The FSE sequence was more prone to movement artefacts.

The benefit of the markedly increased patient throughput made possible by using the FSE sequence outweighs the slight reduction in sensitivity for small lesions.