Primary/Progressive Multiple Sclerosis 3

The aim of our study was to analyse clinical and paraclinical characteristics of patients with Multiple Sclerosis (MS) with previous diagnosis of Primary/Progressive (PP) MS.

According to the Poser's Criteria and further investigate if they fulfil the McDonald's diagnostic criteria for this disorder.

A total of 561 MS patients were registered in the database at the Institute of Neurology, Belgrade, from 1 January 1997 to 31 December 2000 and 63 of them (11.2%) with previous diagnosis of PPMS were analyzed retrospectively.

Male/female ratio was 1.3:1 and mean age at onset 33.2 years.

Most frequent at onset were Pyramidal (in 73% of patients) and sensory symptoms (in 41% of patients); 74.6% of patients had greater than or equal to nine Brain Magnetic Resonance Imaging (MRI) lesions.

Intrathecal OligoClonal ImmunoGlobulin G (IgG) was detected in 96.7% and prolonged Visual Evoked Potentials (VEP) P100 latency in 82.4% of patients.

Of the total study group of 561 patients, 10.2% fulfilled the recently recommended McDonald's diagnostic criteria for the diagnosis of PPMS.

Our findings further support the significance of the Brain/Spinal Cord MRI, CerebroSpinal Fluid and VEP findings for precise diagnostic assessment in patients with suspected PP form of MS.

Magnetic Resonance Imaging (MRI) has become an accepted tool for monitoring therapeutic trials in Relapsing/Remitting and Secondary/Progressive Multiple Sclerosis (MS).

It is however unclear whether such MRI markers are equally applicable to Primary/Progressive MS (PPMS).

Forty-two patients with PPMS were reviewed five years after commencing a two-year MRI and clinical study.

Clinical measures recorded at baseline and five years included both the Expanded Disability Status Scale and the MS Functional Composite.

MRI data collected at baseline and two years included T₁ and T₂ lesion loads, the number of new Brain and Cord lesions, and measures of both Brain and Cord atrophy.

The study demonstrated that both the number of new T₂ lesions and rate of increase in Ventricular volume over two years were modestly predictive of subsequent disease progression and therefore may be useful tools in the testing of new therapeutic agents in PPMS.

Patients with the Primary/Progressive form of Multiple Sclerosis (PPMS) have a unique clinical course and demonstrate additional demographic and imaging features, which separate them from the Relapsing/Remitting form of the condition.

Whether these features indicate a fundamental difference in the underlying pathogenesis of the condition or simply reflect opposite ends of a clinical spectrum is unclear.

What is clear, however, is that this form of MS provides a valuable model of progression, which has the potential to explain this most disabling component of the disease process.

The lack of the hallmark relapses and remissions in PPMS poses diagnostic difficulties, some of which have been addressed by recently published diagnostic criteria.

Following diagnosis, the need for information, specific to this form of MS, must be recognized and addressed.

The relationship of Primary/Progressive Multiple Sclerosis (PPMS) to Relapsing/Remitting MS (RRMS) and Secondary/Progressive MS (SPMS) remains unclear.

Natural history data from a population-based cohort of patients with PPMS followed for approximately 25 years demonstrate remarkable similarities in the progressive phases of PPMS and SPMS.

ImmunoGenetic and Magnetic Resonance Imaging studies in large numbers of patients also fail to differentiate between the two MS categories.

PPMS thus resembles SPMS without the relapses, although the two forms do differ with respect to sex ratio.

An unfavorable outcome in PPMS in predicted by rapid early progression of disability and involvement of three or more systems.

Natural history studies provide information on likely long-term outcomes and can be used in the design and interpretation of clinical trials in PPMS. The evidence that PPMS is distinct remains weak.

Primary/Progressive Multiple Sclerosis (PPMS) is a rather unique form of the more common Relapsing Inflammatory DeMyelinative Disease.

The absence of attacks that typify Relapsing forms of MS imposes special challenges for diagnosis.

But, also provides an opportunity to study the pathogenesis of the more Progressive aspects of the disease process in isolation of confounding transient clinical events.

In this review, recent advances in diagnostic approaches are considered in relationship to baseline data from a large multinational study designed to better characterize and treat this clinical phenotype.

PPMS subjects with CerebralSpinal Fluid (CSF) findings consistent with Intrathecal ImmunoGlobulin production may have a more tissue destructive disease process than those whose CSF lacks evidence of a B-Cell ImmunoPathogenic Disease component.

Diagnosing the 'Primary/Progressive' form of Multiple Sclerosis (PPMS) requires assurance that other conditions that might cause a chronic Inflammatory NeuroDegenerative Central Nervous System (CNS) Disease have been ruled out.

Both imaging and pathological studies have shown that this form of MS tends to be less inflammatory compared with either the Relapsing/Remitting or Secondary/Progressive types.

There are therefore many conditions that cause a slowly progressive wasting of the CNS that might be confused with MS.

The new MS diagnostic scheme has made the presence of 'typical' MS abnormalities in the CerebroSpinal Fluid (CSF) a mandatory first criterion.

But, there may well be individuals that still have PPMS even in the absence of a typical MS CSF.

Here we explore what the CSF can tell about an individual's disease process and outline the current state of the art in terms of CSF analysis. Used properly, the CSF can be very helpful in clarifying a diagnosis of PPMS.

Background
SubClinical Multiple Sclerosis (MS) has been identified incidentally at autopsy; apparently unaffected individuals with an affected twin have demonstrated Magnetic Resonance Imaging (MRI) changes consistent with MS, and 'MRI relapses' are several times more common than clinical relapses.

Case Description
A 39-year-old, right-handed man underwent MRI and PET scanning in 1986 as a 'normal' control in a Parkinson's Disease study, where his father was the proband.

MRI indicated multiple areas of abnormal signal intensity in a PeriVentricular and Gray-White Matter junction distribution.

Repeated clinical evaluations over the next 10 years were unchanged until 1996, when he complained of progressive weakness of the right foot and clumsiness in the right hand.

MRI now indicated a further area of high signal intensity in the right posterior Cord at the level of C5/C6.

There was mild Pyramidal distribution weakness in the right leg with an Extensor Plantar response on the same side.

Over the next five years there has been mild progression in Weakness and Fatigue and intermittent Lhermitte's Phenomenon.

At no stage has there been a history of relapse, CerebroSpinal Fluid examination was normal and Evoked Responses (Visual and SomatoSensory) are normal.

Conclusion
This case demonstrates the phenomenon of SubClinical MS, unusually supported by prolonged clinical and MRI follow-up.

The patient eventually became symptomatic nine years after MRI diagnosis and is following a Primary/Progressive course.

Although MRI is known to be sensitive in identifying subclinical 'attacks', the pattern illustrated here may actually be quite typical of Primary/Progressive MS and is compatible with the later onset seen in this subgroup of patients.

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.