Primary Progressive Multiple Sclerosis, Clinical, Immunological & Radiological Study

Acta Universitatis Tamperensis No. 1893


 

By: Maritta Ukkonen
March 2014
Tampere University Press
Distributed by Coronet Books
ISBN: 9789514493300
138 Pages
$97.50 Paper original


Description:

Multiple sclerosis (MS) that is the most frequent demyelinating disease of the central nervous system (CNS) has very heterogeneous clinical presentations. The majority of patients have relapsing-remitting disease course characterized by episodes of acute exacerbation. Primary progressive MS (PPMS) is a rare subtype of MS which is characterized by a steady progression of irreversible disability from the onset of the disease.

The main goal of this thesis was to identify clinical and immunological features of PPMS and correlate them with magnetic resonance imaging (MRI) findings. The specific aims were the following: 1) to characterize the neurological, cognitive and urological abnormalities in PPMS; 2) to test whether there are specific immunological abnormalities in progressive subtypes of MS; 3) to characterize the volumes of MRI abnormalities in brain and spinal cord in PPMS and 4) to evaluate whether the volumes of focal, diffuse and atrophic central nervous system (CNS) abnormalities in MRI are associated with clinical and immunological features of PPMS.

The study included patients with PPMS (n=28), secondary progressive (SP) MS (22) and healthy subjects (n=20). All patients and controls underwent detailed neurological examination, MR imaging and neuropsychological examinations. Expressions of adhesion molecules (AMs) and the levels of different 17 cytokines/chemokines were measured in blood and cerebrospinal fluid (CSF). MRI was made to patients with PPMS and healthy controls. Furthermore, an urodynamic investigation was made to patients with PPMS.

The most common symptoms in PPMS at the onset of disease included motor, cerebellar or sensory disturbances. The disturbances in motor functions predominated over other neurological dysfunction involving cerebellar, brain stem, sensory, cerebral and visual problems. All patients with PPMS had at least one micturition complaint with urgency and urge incontinence being the most common among them. Urodynamic abnormalities were found in the majority of patients and the most common findings were detrusor sphinkter dyssynergia (DSD) and detrusor hyperreflexia. According to neuropsychological examination the patients with PPMS performed better than those with SPMS in the visual learning test but other significant differences were not found. According to immunological examinations, the expressions of most AMs on blood and CSF immune cells were higher in PPMS than in SPMS or healthy subjects, but no marked differences were detected in the levels of cytokines and chemokines.

Based on MRI, the atrophic changes were pronounced in patients with PPMS compared to healthy controls. Clinicoradiological correlation revealed weak but some correlations between disability measures including ambulation index, arm index and higher cerebral disturbances and MRI findings. Any of the MRI findings did not correlate with expanded disability status scale (EDSS). The number of diffuse brain lesions correlated with attention and information processing, concept formation, reasoning and executive functions, verbal production and learning, visuoperceptual and –constructive functions. All other domains except attention and information processing correlated also with the volume of T2 lesions in brain. The atrophic changes in CNS did not correlated with any of those tests. Among urodynamic findings, detrusor hyperreflexia and DSD correlated with T2 lesion load in brain and hypotonic detrusor was associated with increased numbers of thoracic plaques and with the decreased brain volume. The expression of adhesion molecule VLA-4 on blood lymphocytes and on CSF lymphocytes and monocytes correlated with the total volume of brain lesions and the number of diffuse brain lesions.

In summary, this thesis focusing on the identification of clinical, immunological and radiological characteristics of PPMS, showed only weak correlation between clinical parameters and MRI. Patients with PPMS have decline in several cognitive domains that did not differ markedly from those in SPMS. Micturition problems are very common in PPMS and typical urodynamic findings are DSD and detrusor hyperrefleksia. Upregulated expressions of AMs and some cytokines in blood and CSF compared to controls indicate the presence of persistent inflammation even in neurodegenerative subtypes of MS.