Benign Multiple Sclerosis

  1. Longitudinal follow-up of "Benign" Multiple Sclerosis at 20 years
    Neurology 2007 Feb 13;68(7):496-500

  2. Brain damage as detected by Magnetization Transfer Imaging is less pronounced in Benign than in early Relapsing Multiple Sclerosis
    Brain 2006 Aug;129(Pt 8):2008-16

  1. Multivariate analysis of predictive factors of Multiple Sclerosis course with a validated method to assess clinical events
    J Neurol NeuroSurg Psychiatry 1995 Mar;58(3):300-6

  2. Juvenile Multiple Sclerosis: clinical & prognostic characteristics
    J Pediatr 1998 Apr;132(4):735-7

  3. A clinical and laboratory study of Benign Multiple Sclerosis
    Q J Med 1986 Jan;58(225):69-80

  4. Survival and predictors of disability in Turkish MS patients
    Turkish Multiple Sclerosis Study Group (TUMSSG)
    Neurology 1998 Sep;51(3):765-72

  5. Benign Multiple Sclerosis with childhood Onset
    Rev Neurol (Paris) 1994;150(2):155-6

  6. Onset symptoms as predictors of mortality and disability in MS
    Acta Neurol Scand 1984 Nov;70(5):321-8

  7. Evolution and prognosis of RetroBulbar Optic Neuritis as the initial symptom of Multiple Sclerosis
    Minerva Med 1979 Dec 8;70(55):3797-801

  8. Course and prognosis of Multiple Sclerosis: assessed by data processing of 349 patients
    Brain 1980 Jun;103(2):281-300

  9. Forms of disease progression and prognostic factors in MS
    Psychiatr Neurol Med Psychol (Leipz) 1988 Oct;40(10):588-97

  10. Benign forms of Multiple Sclerosis
    Rev Prat 1991 Sep 15;41(20):1904-7

  11. Clinically Benign Multiple Sclerosis despite large T2 lesion load: Can we explain this paradox?
    Mult Scler 2008 Mar;14(2):205-11

  12. Long term clinical relevance of criteria for designating Multiple Sclerosis as Benign after ten years of disease
    J Neurol NeuroSurg Psychiatry 2008 May 13


Multivariate Analysis Of Predictive Factors Of Multiple Sclerosis Course With A Validated Method To Assess Clinical Events

Trojano M, Avolio C, Manzari C, Calo A, De Robertis F, Serio G, Livrea P
J Neurol NeuroSurg Psychiatry 1995 Mar;58(3):300-6
Univ of Bari, Institute of Clinical Neurology, Bari, Italy
PMID# 7897410; UI# 95205149

The clinical data of 309 patients with definite Multiple Sclerosis were recorded in the European Data Base for Multiple Sclerosis (EDMUS) to determine the prognostic significance of several Demographic and Clinical variables.

An interview with closed questions structured according to standardized criteria of disease phases and courses was used to assess the clinical course. The reliability was evaluated by four trained Neurologists in a sample of 33 patients with Multiple Sclerosis.

Both the within and between rater agreement on data collection was fair to high for the historical variables (K = 0.33-1). Between rater agreement was more variable for the evaluation of 12 different EDMUS event categories (K = 0.3-0.95).

The predictive model for the time to reach a Secondary/Progression, showed that an age at Onset older than 25 (p = 0.006) and an event at Onset followed by disability > or = 3 on the Kurtzke Expanded Disability Status Scale (EDSS; p = 0.004) were the most unfavorable clinical variables in 249 patients with Relapsing/Remitting (180) or Relapsing/Progressive (69) courses.

In the 69 patients with Relapsing/Progressive disease, the time to reach severe disability (EDSS > or = 6) was negatively influenced by a first interval between attacks shorter than one year, a number of bouts with EDSS > 2 in the first two years of the disease, and involvement of the Pyramidal System at Onset (p < 0.05).

In 60 patients with Chronic/Progressive Disease this outcome was negatively influenced by Pyramidal, BrainStem, and Sensory involvement at Onset (p < 0.01).


Juvenile Multiple Sclerosis
Clinical Features And Prognostic Characteristics

Pinhas-Hamiel O, Barak Y, Siev-Ner I, Achiron A
J Pediatr 1998 Apr;132(4):735-7
Sheba Medical Center, Multiple Sclerosis Center, Tel-Hashomer, Israel
PMID# 9580781; UI# 98241882

In a retrospective study we analyzed clinical features and their prognostic significance in 72 patients with Onset of Multiple Sclerosis by the age of 21 years.

In juvenile Multiple Sclerosis disease progression does not depend on age of Onset, Severity of Neurologic Involvement, or PolySymptomatic or MonoSymptomatic Involvement at presentation.


A Clinical & Laboratory Study Of Benign MS

Thompson AJ, Hutchinson M, Brazil J, Feighery C, Martin EA
Q J Med 1986 Jan;58(225):69-80
PMID# 2422674; UI# 86206665

In a hospital-based study of 400 patients with Multiple Sclerosis (MS), 42 per cent of patients who had had MS for 10 years or more had Benign disease. Early age of Onset and a long first remission were significantly associated with a good prognosis.

There was a suggestion that initial presentation with Paresthesia and possibly Optic Neuritis were associated with a Benign prognosis, but the only significant finding was the association between Limb Weakness and a poor outcome (p less than 0.05).

Fewer patients with Benign disease had a Progressive element to their disease than those in the more disabled group (p less than 0.001).

The only laboratory test which was associated with a Benign prognosis was the absence of CSF Myelin Basic Protein in remission.

Abnormalities of Visual Evoked Responses, CSF IgG and peripheral blood T-Lymphocytes appeared to have no value in assessing prognosis in the patients studied.


Survival And Predictors Of Disability
In Turkish MS Patients

Turkish Multiple Sclerosis Study Group (TUMSSG)
Kantarci O, Siva A, Eraksoy M, Karabudak R, Sutlas N, Agaoglu J, Turan F, Ozmenoglu M, Togrul E, Demirkiran M
Neurology 1998 Sep;51(3):765-72
Istanbul University, Cerrahpasa School of Medicine, Dept of Neurology, Turkey
PMID# 9748024; UI# 98418820

To examine the natural history, survival, and prognostic factors in a sample of Turkish MS patients.

This multicenter study included 1,259 definite MS patients diagnosed according to the criteria of Poser et al.

Actuarial analysis of selected disability levels of 3, 6, 8, and 10 achieved with the Expanded Disability Status Scale (EDSS); a multivariate Cox regression analysis for prognostic factors related to time to reach EDSS > or = 6; and Pearson's correlation coefficient for individual factors were performed.

The survival (+/- SE) at 15 years from Onset was 94.6 +/- 2.9%, and at 25 years was 89.0 +/- 5.8%. The disability reached by 15 years was EDSS > or = 3 in 66.4%, EDSS > or = 6 in 41.2%, EDSS > or = 8 in 10.5%, and EDSS = 10 in 5.4%.

The most significant unfavorable prognostic factors were Progressive course (relative risk [RR], 3.73; CI, 2.71 to 5.13) and Sphincter Symptoms at Onset (RR, 1.86; CI, 1.23 to 2.82), followed by male sex, motor symptoms at Onset, and a high attack frequency within the first 5 years.

Primary/Progressive disease was correlated positively with male sex (r = 0.0895, p = 0.001), older age (r = 0.1807, p = 0.000), and Motor (r = 0.1433, p = 0.000) or Sphincter Symptoms (r = 0.1001, p = 0.000) at Onset, unlike Relapsing/Remitting and Secondary/Progressive disease.

Although a slightly better prognosis is observed in the Turkish MS population, early prognostic factors are similar to most of the previous Western series.

Primary/Progressive disease, mostly seen in older men with Motor and Sphincter involvement at Onset, has a worse prognosis and may represent a distinct behavioral variant of MS.


Benign Multiple Sclerosis With Childhood Onset

Pages M, Ondze B, Blard JM
Rev Neurol (Paris) 1994;150(2):155-6
CHU Gui De Chauliac, Service De Neurologie, Montpellier
PMID# 7863156; UI# 95167307

We report a case of Multiple Sclerosis which began at the age of 12 years. Clinical symptoms at Onset were acute, regressive CerebelloVestibular Ataxia and Optic Neuritis.

Twenty-four years later Vertigo, Motor and Sensory deficit of the right lower limb and Grand Mal Seizures developed. CSF and MRI were suggestive of Multiple Sclerosis. The patient is now free of Neurological symptoms with an 8 years' follow-up.


Onset Symptoms As Predictors Of Mortality And Disability In Multiple Sclerosis

Visscher BR, Liu KS, Clark VA, Detels R, Malmgren RM, Dudley JP
Acta Neurol Scand 1984 Nov;70(5):321-8
PMID# 6507042; UI# 85068578

941 cases of Definite/Probable Multiple Sclerosis living in Los Angeles County, California and King and Pierce Counties, Washington in 1970 who had Onset between 1960 and 1969 were followed for mortality and disability through 1980.

Early age of Onset and residence in Washington State were predictors of less rapid and severe subsequent course.

Coordination symptoms at Onset were prognostic of rapid progression to disability and/or early death, whereas early motor weakness was significantly predictive only for Disability.

The presence of Sensory symptoms in addition to Motor and/or coordination symptoms at Onset, however, indicated a better prognosis than coordination and/or Motor symptoms alone.

This observation and the results of regression analyzes indicated that specific groupings of symptoms at Onset were more important for predicting course than the number of symptoms present at Onset.


Evolution & Prognosis Of Retrobulbar Optic Neuritis - Initial Symptom Of Multiple Sclerosis

Ghezzi A, Caputo D, Marforio S
Minerva Med 1979 Dec 8;70(55):3797-801
PMID# 523007; UI# 80100003

In 61 of 300 patients suffering from Multiple Sclerosis, disease Onset was RetroBulbar Optical Neuritis.

Comparing the clinical data of these patients with those of the remaining 239 cases, the following typical features were observed: in patients with Optical Neuropathy, Disease Onset is more frequently acute and course, in the early years of the disease, is in fits and starts.

Recurrence frequency is higher in these patients but not significantly so. Prognosis, deduced from the analysis of degrees of invalidity, does not differ substantially between the two groups.

Current techniques of diagnosing Multiple Sclerosis in patients with RetroBulbar Optical Neuritis are also discussed.


Course And Prognosis Of Multiple Sclerosis Assessed By Data Processing Of 349 Patients

Confavreux C, Aimard G, Devic M
Brain 1980 Jun;103(2):281-300
PMID# 7397479; UI# 80243468

The information of 349 cases of Multiple Sclerosis, seen in a Neurological department over a twenty-year period and followed up for a mean of nine years, was analyzed by computerized data processing.

The mean age at Onset was 30.0 years for the Remittent Onset types (82 per cent cases) and 37.3 years for the Progressive Onset types (18 per cent cases).

    During the course of the disease:
  1. The age of the 'Pure Relapse' stage was 29.2 years
  2. The relapse with sequelae stage 33.9 years
  3. The Progressive Phase 38.0 years

The interval between the first two relapses in the Remittent/Progressive type was important, the shorter the interval the sooner the Progressive Phase occurred. The relapses tended to increase in frequency before the Progressive Phase started.

Using an actuarial graph, 50 per cent of cases could be expected to be moderately disabled (still ambulatory) in six years, and severely disabled (not ambulatory) in eighteen years and dead in thirty years.

Combining a disability score and the duration of the disease prognostic factors could be studied:

  • Associated With A Poor Outcome:
    1. Late onset of the disease
    2. Short interval between the first two relapses
    3. Occurrence of the Progressive Phase
  • No Prognostic Value:
    1. Sex of patient
    2. Symptomatology of the initial relapses
    3. Constituents of the CSF


Forms Of Disease Progression And Prognostic Factors In Multiple Sclerosis

Meyer-Rienecker HJ, Hitzschke B, Buddenhagen F, Lakner K
Psychiatr Neurol Med Psychol (Leipz) 1988 Oct;40(10):588-97
Bereiches Medizin der Wilhelm-Pieck-Universitat Rostock
Abteilung Neurologie,
PMID# 3237865; UI# 89185070

Basing on the diagnostic criteria, an analysis of 687 cases of Multiple Sclerosis (MS) is represented according to the different forms of course, their frequency and the degree of severity.

For the Progressive course - either Secondary after attacks or Primary - a higher proportion of disease with severe disturbances resp. comparatively malignant forms have been found; furthermore, a critical time of progression could be ascertained.

The determination of the Disability Status (using the EDSS) during a longer space of time showed a more unfavorable prognosis for the males. The development of disability was more distinct at Onset of disease in the elder-aged groups.

The problems of uncertain factors influencing the course and prognosis of disease are pointed out in connection with the Heterogeneity of MS, basing on the PathoGenetic components.


Benign Forms Of Multiple Sclerosis

Edan G, Sabouraud O
Rev Prat 1991 Sep 15;41(20):1904-7
Hopital De Pontchaillou, Service De Neurologie, Rennes, France
PMID# 1925374; UI# 92022247

It is still difficult, in 1991, to evaluate precisely the position occupied by Benign forms of Multiple Sclerosis (MS) in the Natural History of the disease.

The reality hidden behind the adjective "Benign" varies from one author to another, and the estimated frequency of these forms is not the same when one refers to epidemiological studies on whole populations or to clinical studies in major hospitals.

There is, however, no doubt that Benign MS does exist, since about 10% of MS patients will suffer, throughout the whole duration of the disease (over 30 years), from no more than moderate disablement with few repercussions on their social and professional life.

These are patients in who MS began when they were 20 to 30 years' old and evolved by Episodes rather than Progressively and whose main symptoms are Optic Neuritis and Sensory Disorders without Pyramidal or Cerebellar Deficit.

Nevertheless, these cases are not easy to recognize a priori: there is no ParaClinical examination that can predict a Benign course in the long term, and an MS which has long been Benign may become worse at any moment.


Clinically Benign Multiple Sclerosis Despite Large T2 Lesion Load: Can We Explain This Paradox?

Strasser-Fuchs S, Enzinger C, Ropele S, Wallner M, Fazekas F
Mult Scler 2008 Mar;14(2):205-11
Medical University, Division of NeuroRadiology, Department of Neurology, Graz, Austria
PMID# 17986507

Magnetic Resonance Imaging (MRI) techniques such as Magnetization Transfer Imaging and Magnetic Resonance Spectroscopy (MRS) may reveal otherwise undetectable tissue damage in Multiple Sclerosis (MS).

And, can serve to explain more severe disability than expected from conventional MRI.

That an inverse situation may exist where non-conventional quantitative MRI and MRS metrics would indicate less abnormality than expected from T2 lesion load to explain preserved clinical functioning was hypothesized.

Quantitative MRI and MRS were obtained in 13 consecutive patients with clinically Benign MS (BMS; mean age 44+/-9 years) despite large T2 lesion load and in 15 patients with Secondary/Progressive MS (SPMS; mean age 47+/-6 years) matched for disease duration.

The Magnetization Transfer Ratio (MTR), Magnetization Transfer Rate (k-for), Brain Parenchymal Fraction (BPF) and Brain metabolite concentrations from proton MRS were determined.

BMS patients were significantly less disabled than their SPMS counterparts (mean Expanded Disability Status Score: 2.1+/-1.1 versus 6.2+/-1.1; P < 0.001) and had an even somewhat higher mean T2 lesion load (41.2+/-27.1 versus 27.9+/-24.8 cm3; P=0.19).

Normal-Appearing Brain Tissue Histogram metrics for MTR and k-for, mean MTR and k-for of MS Lesions and mean BPF were similar in BMS and SPMS patients.

Levels of N-AcetylAspartate, Choline and Myoinositol were comparable between groups.

This study thus failed to explain the preservation of function in our BMS patients with large T2 lesion load by a higher morphologic or metabolic integrity of the Brain Parenchyma. Functional compensation must come from other mechanisms such as Brain plasticity.


Long Term Clinical Relevance Of Criteria For Designating Multiple Sclerosis As Benign After Ten Years Of Disease

Costelloe L, Thompson A, Walsh C, Tubridy N, Hutchinson M
J Neurol NeuroSurg Psychiatry 2008 May 13
St. Vincent's University Hospital, Dublin, Republic of Ireland
PMID# 18477712

To determine the long term outcome of a cohort of 436 MS patients seen in 1985 and long-term predictors of Benign MS.

The initial 1985 group of 436 patients with Possible MS, including 53 Benign patients were followed for 21 years.

Disability was recorded using the EDSS. Survival from disease onset was calculated. The indicators of Benign MS in the initial 1985 cohort and in the survivors in 2006 were determined.

Of the original 436 patients, the 21-year follow-up outcome in 397 (91%) was established.

The diagnosis of MS was incorrect in 41/397 (10%) of the whole cohort and in 2/53 (4%) of the Benign group. Median survival of 356 MS patients was 43.6yrs from disease onset.

Of 47/51 (92%) Benign MS patients followed in 2006 seven remained Benign, 18 had died, and 22 were disabled.

Median survival advantage for the 47 Benign in 1985 compared to the 88 not Benign, when corrected for age was six years (p < 0.08).

In 2006, 40/356 (11%) patients had a Benign outcome at a mean follow up of 26.1 yrs.

    A Benign course was significantly associated with:
  1. Female sex,
  2. Younger age of onset and
  3. Absence of motor symptoms at presentation

Although designating patients as having a Benign course after 10 years has a poor predictive value; three factors at presentation indicate a better prognosis.

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