Clinical, MRI, CSF and electrophysiological findings in different stages of multiple sclerosis

Effective therapy in the earliest stages of multiple sclerosis (MS) demands early correct diagnosis. Retrospective analysis included 130 patients (90 women) with a median age of 35.5 years, median duration of the disease of 2 years and median EDSS score of 3.0. Twenty-seven patients had clinically isolated syndrome (CIS) suggestive of MS, 66 relapsing-remitting (RR) MS, 19 secondary progressive (SP) MS and 18 primary progressive (PP) MS. The predominant symptoms were sensory in 52% of the patients with CIS compared to 27% in patients with RRMS, whereas they were more often motor in patients with PPMS. Patients with CIS had higher CSF cell counts than patients diagnosed in later stages of the disease and oligoclonal bands were found in 89% of all patients without statistically significant differences between the subgroups. Prolonged latencies of visual evoked potentials (VEP) were found in only 29% of patients with CIS compared to 66% in RRMS, 75% in SPMS and 65% of PPMS patients. Fifty-six percent of patients with CIS, 88% with RRMS, 74% with SPMS and 78% of patients with PPMS fulfilled modified the Barkhof et al. MRI criteria at the time of diagnosis. Patients in early MS often present with sensory symptoms. Brain MRI can be inconclusive in over 40% of patients with CIS but the elevated CSF cell count and positive oligoclonal bands are helpful in establishing the diagnosis of CIS suggestive of MS. In later stages of the disease the combination of clinical features, MRI, prolonged VEP latencies and positive CSF oligoclonal bands secures the correct diagnosis.     

CSF oligoclonal bands, MRI, and the diagnosis of multiple sclerosis

In this retrospective study, the results from investigations (MRI, evoked potentials, alkaline oligoclonal bands [OBs] in CSF) in 94 patients with clinical suspicion of demyelinative disease were evaluated to assess their impact on diagnosis. Forty-three patients were diagnosed as having definite MS, 10 probable MS, and 9 possible MS. MRI findings strongly suggestive of MS were evident in 52/62 (84%) patients, while 47/62 (76%) patients demonstrated OBs in their CSF. In 63% of patients both abnormalities were present. Patients with no OBs in their CSF were on the average older, were more often male, had experienced their first symptoms at a later age, and suffered more often from the chronic-progressive form of the disease than those with a positive CSF finding.     

Detection of oligoclonal free kappa chains in the absence of oligoclonal IgG in the CSF of patients with suspected multiple sclerosis

BACKGROUND: Oligoclonal free kappa bands are present as frequently as oligoclonal IgG bands in the cerebrospinal fluid (CSF) from patients with definite multiple sclerosis (MS) and can even occur in the absence of oligoclonal IgG. As such, they too are markers of an ongoing intrathecal immune process. OBJECTIVES: To determine how frequently oligoclonal free kappa bands are detectable in the CSF from patients with clinical signs and symptoms suggestive of MS in the absence of CSF restricted oligoclonal IgG. METHODS: An immunoaffinity mediated immunoblotting technique specific for free kappa chains was used, after isoelectric focusing of paired CSF and serum samples from 33 patients with clinical signs and symptoms suggestive of MS but without CSF oligoclonal IgG. CSF data were correlated with MRI results in the context of the new diagnostic criteria from McDonald et al. RESULTS: Eighteen CSF samples contained oligoclonal free kappa bands (54%), mainly from patients with motor dysfunction (83%) and optic neuritis (64%). All patients with a positive MRI according to Barkhof's criteria (n = 6) had free kappa bands in their CSF. CONCLUSIONS: (1) Oligoclonal free kappa bands in the CSF are related to the dissemination of MS lesions; (2) such bands should be looked for in oligoclonal IgG negative CSF, and (3) the presence of free kappa bands in the CSF may be a substitute for oligoclonal IgG in the McDonald's criteria for diagnosis of MS.     

Multiple sclerosis. Magnetic resonance imaging, evoked potentials and cerebrospinal fluid analysis

We have studied 27 patients with multiple sclerosis (22 definite, 5 probable) by magnetic resonance imaging (MRI), visual evoked potentials (VEPs), brainstem auditory evoked potentials (BAEPs), and oligoclonal bands (OBs) in cerebrospinal fluid (CSF), MRI was altered in 92.5% of the cases, the presence of OBs in CSF was revealed in 73.1% of the examined patients, the frequency of evoked potentials (EPs) alteration was VEPs = 59.3% and BAEPs = 29.6%, at least one of the two EPs occurred positive in 66.6% of the cases. Our data confirm the more sensitive value of MRI compared with OBs and EPs studies in assessing MS, and stress the utility of the combined use of these tests.     

Failure to develop multiple sclerosis in patients with neurologic symptoms without objective evidence

BACKGROUND: Many patients referred to multiple sclerosis (MS) centers with symptoms suggestive of MS are found to have normal neurologic examinations, normal or non-specific brain magnetic resonance imaging (MRI) scan findings, and normal cerebrospinal fluid (CSF). Persistent symptoms often lead to multiple consultations and repeated diagnostic investigations. We performed a study to evaluate the diagnostic utility of repeated evaluations in patients with normal initial assessments and persistent neurologic symptoms. METHODS: 143 patients were evaluated initially and 109 returned for a second evaluation after a mean interval of 4.4 years. RESULTS: All 143 patients had normal initial examinations, brain MRI scans, screening blood tests, and CSF studies. Spinal cord imaging was normal in all patients tested (cervical cord, n = 126; 88.1%; thoracic cord, n = 58; 40.6%). Evoked potential studies were abnormal in a small percentage of patients: visual evoked potentials, VEP (8.1%), somatosensory evoked potentials, SSEP (4.9%), and brainstem auditory evoked potentials, BAEP (2.8%). All follow-up patients (n = 109) had normal examinations and MRI scans. Repeat CSF studies (n = 35; 32.1%) and spinal cord imaging (cervical cord n = 57; 52.3%; thoracic cord n = 32; 29.4%) were normal in all follow-up patients tested. No patients at initial presentation or at follow-up fulfilled diagnostic criteria for MS. CONCLUSIONS: PATIENTS: and clinicians may be reassured that persistent neurologic symptoms in the absence of objective clinical evidence do not lead to the development of MS. Costly serial investigations should be carefully considered, particularly in the presence of normal neurologic examination at follow-up.     

CSF abnormalities can be predicted by VEP and MRI pathology in the examination of optic neuritis

Optic neuritis (ON) is linked to multiple sclerosis (MS). The presence of white matter lesions on cerebral magnetic resonance imaging (MRI) predicts the risk of MS after ON with considerable accuracy. Oligoclonal bands (OCB) are present in 95?% of MS patients, and a lumbar puncture can also be valuable in the evaluation of patients with ON. We analyzed CSF findings in patients referred with ON in the context of MRI and visual evoked potential (VEP) pathology. We assessed the possible contributory role of a lumbar puncture and weigh this against disadvantages of the procedure. Between February 2003 and November 2011, 505 patients were referred by ophthalmologists to the Clinic of Optic Neuritis, Glostrup Hospital, University of Copenhagen. None had MS prior to referral. A total of 437 were included in the study, and all underwent MRI, a lumbar puncture and VEP. Patients with other organic causes of their symptoms and patients with >3?months between onset and tests were excluded. All files were reviewed retrospectively. CSF leukocytes and the IgG index were elevated in 33 and 41?%, respectively, and OCBs were detected in 61?% of patients. CSF abnormalities correlated strongly with VEP and MRI (p?<?0.0001). Patients with normal VEP and MRI had a 96?% probability of a normal lumbar puncture. The contributory role of a lumbar puncture in the evaluation of ON seems negligible when patients have a normal VEP and MRI. We suggest that all patients should be evaluated with VEP and MRI before deciding on a lumbar puncture.     

Correlation between multimodal evoked potentials and magnetic resonance imaging in multiple sclerosis

Summary Sixty multiple sclerosis (MS) patients (33 definite, 13 probale and 14 suspected were investigated by computed tomography (CT), magnetic resonance imaging (MRI), multimodality evoked potentials (EPs) and cerebrospinal fluid (CSF) electrophoresis. MRI abnormalities were found in 50 cases, while at least one abnormal evoked potential was detected in each of 52 cases. Brain-stem auditory evoked potentials were more sensitive than MRI for the detection of brainstem involvement. All the patients with oligoclonal bands had abnormal MRI and none of the patients with normal MRI had oligoclonal bands in the CSF. The number and the extent of MRI lesions were significantly correlated with the duration of disease and with the degree of disability. Our observations stress the importance of the combined use of MRI and EPs in detecting silent CNS lesions in MS patients.     

A retrospective study of multiple sclerosis in Siriraj Hospital, Bankok, Thailand

OBJECTIVE: To determine the demographic and clinical data of Thai multiple sclerosis (MS) patients. METHODS: A retrospective study of 72 patients attending the MS clinic at Siriraj Hospital, Mahidol University, Thailand between January 1997 and June 2004. RESULTS: Fifty-eight patients (81%) were classified as clinically definite MS, 5 (7%) as Devic's syndrome, and 9 (13%) as possible MS. There were 62 females (86%) and 10 males (14%). Age at onset was 33 +/- 12 years with a mean relapse rate of 1.2 +/- 1.0 attacks per annum. None had a family history of MS. Visual impairment (53%) was the most common manifestation. Only 16% had classic (western) form of MS. Positive oligoclonal bands were found in 21%, visual evoked potentials with a typical delayed latency in 28%. MRI brain lesions compatible with McDonald's criteria were seen in only 24%, and spinal MRI brain longer than 2 vertebral bodies in 62%. The mean Kurtzke's Expanded Disability Status Scale (EDSS) was 3.0. CONCLUSIONS: Thai MS patients had much more female occurrence, no family history, common optico-spinal form, long spinal MRI lesions and low positive CSF oligoclonal bands.     

Diagnostic investigations in MS: which is the most sensitive?

In an attempt to establish the efficacy of the different diagnostic tests, 41 multiple sclerosis (MS) patients at different stages of the disease were studied by means of visual evoked potential (VEP) recording, T-lymphocyte subset determination cerebrospinal fluid (CSF) analysis and magnetic resonance (MR) imaging. MR and CSF oligoclonal bands (OB) were the most sensitive techniques for the diagnosis of MS, being positive in 88% of patients, while VEP and helper/suppressor (H/S) T-cell ratio were altered in 54% and 46% of patients respectively. Low significant agreement coefficient were found among the 4 tests and the major value, even though "fairly" significant, was between MR and OB.     

Early onset MS under the age of 16: clinical and paraclinical features

MS in juvenile patients under the age of 16 occurred in 31 (5%) of our whole MS population of 620 patients in the time from 1975-1991. It does not differ clinically from the disease as observed in 72 patients with later onset MS in respect to symptoms at onset, course, progression rate, rate of relapses and abnormalities in CSF and MRI. However, fever, headache, nausea and vomiting with pleocytosis in CSF during the first episode and development of oligoclonal bands with passage of time may be characteristic in some juvenile patients. The presence of oligoclonal bands and MRI results are of high diagnostic value in this special group of patients.     

Sensory (VEP, BAEP, SEP) and motor-evoked potentials, liquoral and magnetic resonance findings in multiple sclerosis

In order to define the most suitable instrumental protocol for the diagnosis of multiple sclerosis (MS), 41 patients with definite (D = 14), probable (P = 14) and suspected (S = 13) MS were examined with CSF immunology, brain MRI and multimodal evoked potentials. The central motor tracts were also tested. The following alteration rates were found: MRI = 78%, CSF = 63.6%, VEP = 70.0%, median nerve SEP = 50%, peroneal nerve SEP = 68.0%, BAEPs = 35.7%, motor-evoked potentials (MEPs) = 74.0%. Altogether, EPs were abnormal in 90% of cases. Normal MRI with altered EPs were found in 22% of cases, whilst a normal EP battery with defective CSF or MRI findings were found in 7%. Twenty-six out of 27 patients with P or S forms were reclassified into a D one when considering EPs and MRI features.     

Cerebrospinal fluid immunoglobulins and multiple sclerosis. Correspondence with magnetic resonance imaging and visually evoked potential changes

The clinical (disability) and paraclinical (visually evoked potential [VEP]/magnetic resonance imaging [MRI]) data of patients with definite or probable multiple sclerosis (MS) were compared with their cerebrospinal fluid (CSF) immunoglobulins taken within the same period of time. For patients with definite diagnosis by the Schumacher criteria (n = 61) we found significant correlations between CSF immunoglobulin content (absolute gamma-globulin value [aggv]) and quantified MRI factors (r = .47), between aggv and the sum of VEP latencies of both eyes (r = .53), and also between MRI and VEP changes (r = .62). This was not true for the patients with a probable MS diagnosis and for patients with first attacks. No correlations were evident between aggv and disability status or duration of the illness. The results give support to recent neuropathologic and experimental findings in animals indicating close pathogenic connections between CSF immunoglobulins and demyelination in MS.     

Clinical characteristics of patients with late-onset multiple sclerosis

We evaluated clinical presentation, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) in patients with late-onset multiple sclerosis (LOMS). Fifty-two patients with definitive multiple sclerosis (MS) diagnosed after the age of 50 years were identified between 1991 and 2002. Data pertaining to clinical characteristics, CSF analysis, and cerebral and spinal MRI were compared with those of 52 young-onset MS (YOMS) patients matched for sex and disease duration. Mean age at the time of diagnosis was 57 years in the LOMS group - the oldest patient was 82 - and 29 years in the YOMS group. Motor symptoms were significantly more often present in the LOMS than in patients with YOMS (90 % vs. 67 %, p = 0.014). Visual symptoms, residual signs of optic neuritis, and dysarthria were less frequent for LOMS. Sensory symptoms, ataxia, oculomotor symptoms, cognitive disorder, or fatigue did not differ between both groups. The majority of LOMS patients (83 %) had a primary progressive disease course, whereas 94 % of the YOMS group had a relapsing-remitting course. MRI showed typical multifocal supratentorial (LOMS vs. YOMS: 96 % vs. 98 %) and infratentorial (44 % vs. 62 %) lesions without significant group differences. Of particular interest, spinal lesions were more common (81 %) in LOMS compared to YOMS (48 %, p = 0.024), and cerebellar lesions were less frequent in the LOMS group (11 % vs. 44 %, p = 0.001). Gadolinium-enhanced lesions were initially present in less LOMS patients (15 %) than in YOMS (63 %, p < 0.001). CSF analysis revealed pleocytosis less frequently in LOMS (34 %) compared to YOMS (67 %, p = 0.006) but oligoclonal banding occurred without in both groups without differences. YOMS patients responded to corticosteroids (93 %) to a significantly greater degree than LOMS patients (73 %; p = 0.004). For individuals who develop LOMS, a primary progressive course is frequent, with motor symptoms as the prominent feature. Vigilance is necessary to recognise MS in this population because of its unusual presentation.     

Prospective study of patients presenting with acute partial transverse myelopathy

Abstract. Background: The clinical and radiological characteristics of myelopathy in multiple sclerosis (MS) are relatively well known. Nevertheless, it remains difficult for the clinician to ascertain conversion to MS after a first episode of acute partial transverse myelopathy (APTM). Objective: The aims of this study were to define predictive factors for conversion to clinically definite MS after an APTM and to define predictive factors for disease severity. Patients and methods: Between 1994 and 2001, we prospectively included 55 patients presenting with a first episode of APTM. Three patients were lost during the follow-up. We evaluated clinical signs, spinal cord and brain MRI, cerebrospinal fluid (CSF) and visual evoked potentials on admission.After a mean followup of 35 months (range 12–86), we evaluated the diagnosis and, among the MS group, the severity of the disease. Results: Of the 52 APTM patients who completed the study, 30 became clinically definite MS. The predictive factors for conversion to MS were: initial sensory symptoms, latero-posterior spinal cord lesion, abnormal brain MRI and oligoclonal bands in CSF. In the MS group, the number of spinal cord lesions on MRI was the only predictive factor for a poor outcome, being statistically correlated with a higher number of relapses. Conclusion: On the basis of our results, we propose that, in patients with APTM, sensory symptoms, oligoclonal bands and brain MRI are predictive factors for subsequent conversion to clinically definite MS and that within the latter patients the number of spinal cord lesions on MRI is the only predictive factor for a poor outcome.     

Optic neuritis: findings on MRI,CSF examination and HLA class II typing in 60 patients and results of a short-term follow-up

Optic neuritis (ON) is a common first manifestation of multiple sclerosis (MS), and examination of patients with ON provides opportunities to study the early clinical stages of MS. This prospective study compares results of brain magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) examinations and HLA-Dw2 phenotyping in 60 consecutive patients with ON. At a median of 17 days after the onset of ON, 69% had oligoclonal IgG bands, and at a median on 79 days after onset, 53% had multiple ( 3) white matter lesions on MRI. Subgroup analyses revealed that MRI abnormalities and oligoclonal IgG bands were equally common in patients examined early or late after the onset of ON. Strong correlations were found between the presence of MRI abnormalities and oligoclonal IgG bands. The HLA-Dw2 phenotype was significantly increased in ON patients compared with controls, but also significantly different from a group of MS patients from the same geographical area. A significant relation was found between Dw2 phenotype and oligoclonal IgG bands. During a mean follow-up time of about 2 years, the diagnosis in 17 of the patients changed to clinically definite MS. Initially, 16 of them had oligoclonal IgG bands and 12 had three or more MRI lesions. Both MRI and CSF studies are important diagnostic tools in the work-up of ON patients.     

Diagnostic value of magnetic resonance imaging in multiple sclerosis]

Brain MRI findings in 16 clinical cases of MS were compatible with multiple lesions in the brains in 14 cases. Cerebral lesions were detected in 12 cases without symptoms or signs referable to the cerebral hemispheres. When compared with t*he findings CT scannings, evoked potentials, and oligoclonal bands in the CSF, MRI findings appeared to be the most effective means for confirming the diagnosis of MS, but they would not indicated the course, the times of relapse and the activity of the disease process.     

Oligoclonal free kappa and lambda bands in the cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. An immunoaffinity-mediated capillary blot study.

We describe an affinity-mediated capillary blotting technique for the detection of free kappa or lambda light chains in native cerebrospinal fluid (CSF) after isoelectric focusing in agarose gel. Interferences by light chains bound to immunoglobulins were carefully excluded. An absolute amount of 20-50 ng of free kappa or lambda Bence-Jones proteins were detectable by this method, under the form of several discrete bands with isoelectric points between 5 and 8.5. No free light chains were observed in CSF and sera from patients without neurological disorders (n = 26). Such bands were present in most CSF samples in the case of central nervous system (CNS) infections, except in aseptic meningitis. In a group of 48 multiple sclerosis (MS) patients, 44 (92%) displayed oligoclonal free kappa bands restricted to the CSF; oligoclonal IgG bands were observed in 40 cases, and oligoclonal free lambda bands in 33. In this group, the presence of CSF free light chain bands was highly correlated with their absolute levels (p less than 0.001). In other neurological diseases (n = 44), oligoclonal free kappa and free lambda bands were detected much more rarely, in seven (16%) and four (9%) cases respectively. Surprisingly, the CSF from three unrelated patients with Huntington's disease (out of five tested) contained both oligoclonal IgG and free kappa bands.     

Relation between benign course of multiple sclerosis and low-grade humoral immune response in cerebrospinal fluid.

The prognosis in multiple sclerosis (MS) is related to the presence of an abnorma humoral immune response within the central nervous system: 14/17 MS patients (82%) without oligoclonal CSF IgG displayed no or slight disability after a mean duration of MS of 17 years, while 53% of 88 patients with oligoclonal CSF IgG had a benign course after a mean duration of 13 years (p less than 0.05). A benign course also was more often accompanied by a normal CSF IgG index. MS patients without oligoclonal CSF IgG had elevated CSF/serum ratios of albumin in 6%, and of the complement factors C3 in 0% and C4 in 6%, as against 20%, 27% and 37%, respectively, in MS patients with oligoclonal CSF IgG.     

Conversion to multiple sclerosis after a clinically isolated syndrome of the brainstem: cranial magnetic resonance imaging,cerebrospinal fluid and neurophysiological findings

BACKGROUND AND AIM: Conversion to multiple sclerosis (MS) after optic neuritis and myelitis has been thoroughly studied; however, limited data are available regarding conversion to MS after a clinically isolated syndrome of the brainstem (CISB). The aim of this study was to investigate conversion to MS in patients with CISB. METHODS: Fifty-one patients with CISB were prospectively studied. Cranial magnetic resonance imaging (MRI), determination of oligoclonal bands (OBs) in the cerebrospinal fluid (CSF) and evoked potentials (EPs) were performed. Based on conversion to MS at follow-up, the sensitivity, specificity, accuracy and positive and negative predictive values of these tests were calculated. RESULTS: Clinically definite MS developed in 18 (35%) patients after a mean follow-up of 37 months. Paty's MRI criteria showed a sensitivity of 89%, a specificity of 52% and an accuracy of 65%; Fazekas' criteria showed a sensitivity of 89%, a specificity of 48% and an accuracy of 63%; Barkhof's criteria showed a sensitivity of 78%, a specificity of 61% and an accuracy of 67%. The presence of OBs in the CSF showed a sensitivity of 100%, a specificity of 42% and an accuracy of 63%. No differences for neurophysiological parameters were found between patients who did and those who did not convert to MS. CONCLUSION: Fulfilling Paty's, Fazekas' or Barkhof's MRI criteria and the presence of OBs in the CSF are associated with a higher risk of conversion to MS in patients with CISB. Determination of OBs in the CSF has the greatest sensitivity of all tests. Barkhof's MRI criteria have greater specificity (although less than previously published for mixed cohorts of clinically isolated syndromes) in predicting conversion to MS for CISB than either Paty's or Fazekas' criteria.     

Paraclinical tests in acute-onset optic neuritis: basal data and results of a short follow-up

Up to now it is still doubtful whether there is a real risk of developing multiple sclerosis (MS) after initial monosymptomatic optic neuritis (ON). In this study we evaluated 43 patients with isolated acute-onset ON, in order to demonstrate the presence of oligoclonal bands (OBs) in the cerebrospinal fluid (CSF) and any additional clinically silent central nervous system (CNS) lesions. All examinations were performed from 5 days to 4 months (mean 43 days), from the onset of visual disturbances. Brain magnetic resonance imaging (MRI) detected white matter areas with increased signal in 21 patients (49%), while somatosensory and brainstem auditory evoked potentials revealed CNS abnormalities in only 5 patients (12%). OBs were present in the CSF of 20 patients (46%). Visual evoked potentials were abnormal in 39 patients (91%). Seven out of the 37 patients (19%) with at least one year follow-up, (mean duration of the follow-up = 32 months, range = 12-74), developed clinically definite MS (CDMS). All 7 patients had positive brain MRI and 6 had positive CSF examination at the basal evaluation. Our data suggest that MRI and CSF-OBs are the most reliable means of identifying patients with isolated ON who subsequently develop CDMS. They may therefore have a predictive value in defining MS risk.