Recovery following acute exacerbations of multiple sclerosis: from impairment to quality of life.

To observe the pattern of recovery after treatment with intravenous Methylprednisolone (i.v. MP) for a relapse of multiple sclerosis (MS), and to determine the best time to plan further interventions such as rehabilitation, we assessed consecutive outpatients (n = 24) treated with i.v. MP for a relapse over a period of 12 weeks. Outcomes measures used were the Expanded Disability Status Scale (EDSS), the Incapacity Status Scale (ISS), the MOS Short Form-36 (SF-36), the Mental Health Inventory (MHI), and the MS-Related Symptom Checklist (MSSCL). There was statistically significant early improvement of EDSS and ISS scores, which was sustained until week 12, and significant improvement of MHI and MSSCL scores between 4 and 12 weeks. Although trends for improvement of scores reflecting the same pattern of recovery were observed with the SF-36 physical and mental composites, these changes did not reach statistical significance. Our results suggest that improvement of impairments and disability after treatment with i.v. MP for a relapse of MS occurs early, while improvement of subjective health status is delayed. Even after maximum improvement is reached, patients are left with multiple symptoms and functional limitations, and may benefit from additional rehabilitative interventions.     

Occipital Lobe Seizures as the Major Clinical Manifestation of Reversible Posterior Leukoencephalopathy Syndrome: Magnetic Resonance Imaging Findings

Summary: Purpose: Reversible posterior leukoencephalopathy syndrome (RPLS) is an increasingly recognized brain disorder most commonly associated with malignant hypertension, toxemia of pregnancy, or the use of immunosuppressive agents. When associated with acute hypertension, RPLS typically occurs concurrently with the fulminant clinical syndrome of hypertensive encephalopathy. We describe occipital lobe seizures, in the setting of only moderate elevations of blood pressure, as the major clinical manifestation of RPLS.
Methods: Two patients from the Dent Neurologic Institute are presented with clinical and magnetic resonance imaging(MRI) correlation.
Results: New onset secondarily generalized occipital seizures were noted, with MRI findings consistent with RPLS. Both of the patients had chronic renal failure and a moderate acute exacerbation of chronic hypertension. Other features of hypertensive encephalopathy were lacking, such as headache, nausea, papilledema, and an altered sensorium. Magnetic resonance imaging (MRI) showed edematous lesions primarily involving the posterior supratentorial white matter and corticomedullary junction, consistent with RPLS. With lowered blood pressure, the MRI lesions resolved and the patients became seizure-free without requiring chronic anticonvulsant therapy.
Conclusions: Occipital seizures may represent the only major neurologic manifestation of RPLS due to acute hypertension, especially in patients with renal failure. Other evidence of hypertensive encephalopathy, such as cerebral signs and symptoms, need not be present. Blood pressure elevations may be only moderate. Early recognition of this readily treatable cause of occipital seizures may obviate the need for extensive, invasive investigations. Despite the impressive lesions on MRI, prompt treatment of this disorder carries a favorable prognosis.     

Diversity and plasticity of self recognition during the development of multiple sclerosis.

Recent studies using murine animal model systems indicate that clinical progression of autoimmune disease may be due to the sequential accumulation of neoautoreactivity characterized by extensive plasticity of self recognition. In the present study, we addressed the question of whether a similar paradigm of self recognition is implicated in the development of multiple sclerosis (MS), a demyelinating disease with a presumed autoimmune etiology. Our approach was to determine serial changes over a 12-18-mo period in response to an epitope-mapping series of 265 12-mer peptides of myelin proteolipid protein (PLP) by patients with isolated monosymptomatic demyelinating syndromes (IMDS), a group of distinct clinical disorders with variable rates of progression to MS. Our data showed that an extensive array of proteolipid protein peptides could elicit autoreactivity. Moreover, differential autoreactive patterns were evident within IMDS patient subpopulations. Monocentric monophasic IMDS patients with no evidence of prior subclinical disease typically showed fully sustained autoreactivity characterized by extensive plasticity, epitope focusing, shifting, and spreading of responses to new self determinants. In contrast, multicentric monophasic IMDS patients with putative evidence of prior asymptomatic lesion formation typically showed partially sustained autoreactivity characterized by abrupt abrogation of responses to an extensive array of self determinants. No sustained autoreactivity was observed in normal control subjects or in patients with other neurologic diseases. Our results indicate that self recognition associated with the development of MS is a developmental process characterized by autoreactive diversity, plasticity, and instability.     

Steady-state pharmacokinetics of tacrine in patients with Alzheimer's disease

Neurochemical studies of Alzheimer's disease (AD) suggest deficiencies in the cholinergic system. We evaluated the steady-state pharmacokinetics of tacrine (Cognex), an oral cholinesterase inhibitor, in 12 patients with AD. Patients sequentially received nine doses of 10 mg, 20 mg, and 30 mg of tacrine every 6 hours. Blood samples were collected until 24 hours after the final dose. Plasma tacrine concentrations were measured using a validated high-performance liquid chromatographic method. Mean maximum plasma concentrations (Cmax) were 5.1 ng/ml, 20.7 ng/ml, and 33.9 ng/ml following administration of 10 mg, 20 mg, and 30 mg doses, respectively. Corresponding mean values for steady-state area under the curve (AUC) were 19.7 ng/ml, 82.9 ng/ml, and 139 ng/ml.hr. Dose-normalized Cmax and AUC values after administration of the 20 mg and 30 mg doses of tacrine were comparable to each other but were significantly greater (p less than .05) than those after the 10 mg doses. The apparent elimination half-life was approximately 3.4 hours for all dosing regimens. Dose-dependent increases in Cmax and AUC values in patients with AD were similar to those previously reported in normal volunteers. The mechanism of the nonlinearity in tacrine pharmacokinetics is unknown.     

Regression and spreading of self-recognition during the development of autoimmune demyelinating disease.

The autoimmune T cell repertoire in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) is characterized by CD4(+)T cells of the Th1 phenotype that recognize peptide determinants of central nervous system (CNS) myelin proteins in an MHC class II-restricted manner. Our recent studies and those performed by others have shown that progression to chronicity in EAE and MS is accompanied by a broadening of the T cell repertoire with time. This acquired neo-autoreactivity is commonly referred to as epitope spreading and is presumably the result of endogenous priming to new self-determinants during the CNS inflammation that accompanies disease onset and relapse. In the present study we extend our earlier observations by showing that disease progression in both EAE and MS is accompanied by two concurrent events, viz. (1) the spontaneous regression of the primary established autoimmune repertoire associated with disease onset, and (2) the emergence of the epitope spreading cascade associated with disease progression. Our data show that disease initiation and disease progression in both EAE and MS are typically associated with distinctly different autoimmune T cell repertoires. Our data support the view that the natural development of self-recognition during autoimmune disease may best be understood when considered in the temporal context of an 'epitope du jour' and 'moving target' perspective.     

Diagnostic potential of plasma carboxymethyllysine and carboxyethyllysine in multiple sclerosis

Background  

This study compared the level of advanced glycation end products (AGEs), N -(Carboxymethyl)lysine (CML) and N -(Carboxyethyl)lysine (CEL), in patients with multiple sclerosis (MS) and healthy controls (HCs), correlating these markers with clinical indicators of MS disease severity.     

Fatigue in multiple sclerosis: cross-sectional correlation with brain MRI findings in 71 patients.

Fatigue is an unexplained but common and disabling symptom in MS. We assessed fatigue in 71 patients with MS and identified MS-fatigue (MSF) and MS-nonfatigue (MSNF) groups. Fatigue severity did not correlate with regional or global MRI plaque load or atrophy assessed by conventional sequences. No significant differences were noted in any MRI measures between MSF and MSNF groups. We suggest that brain MRI disease topography or severity does not explain fatigue in MS and that fatigue is likely due to mechanisms poorly characterized by conventional MRI.     

ESUR guidelines for MR imaging of the sonographically indeterminate adnexal mass: an algorithmic approach

A significant proportion of adnexal masses detected by sonography are indeterminate. Either their organ of origin is uncertain or it is unclear whether their nature is benign or malignant. MR imaging of the sonographically indeterminate adnexal mass can resolve most of these uncertainties. Most indeterminate masses result from common benign conditions and women with such masses can avoid unnecessary or inappropriate surgery. For the minority of women whose masses are malignant, use of MR imaging rather than a ‘wait and watch’ strategy of repeat ultrasound (US) results in a more timely diagnosis. There are simple diagnostic steps in the MR imaging assessment which direct an algorithmic and problem-solving approach based on signal characteristics and morphology. MR imaging should provide a more timely diagnosis and, thereby, guide the management of the patient with reduced costs of investigation and treatment.     

A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG).

OBJECTIVE: To determine if progressive brain atrophy could be detected over 1- and 2-year intervals in relapsing MS, based on annual MR studies from the Multiple Sclerosis Collaborative Research Group (MSCRG) trial of interferon beta-1a (Avonex). METHODS: All subjects had mild to moderate disability, with baseline expanded disability status scores ranging from 1.0 to 3.5, and at least two relapses in the 3 years before study entry. Atrophy measures included third and lateral ventricle width, brain width, and corpus callosum area. RESULTS: Significant increases were detected in third ventricle width at year 2 and lateral ventricle width at 1 and 2 years. Significant decreases in corpus callosum area and brain width were also observed at 1 and 2 years. Multiple regression analyses suggested that the number of gadolinium-enhancing lesions at baseline was the single significant contributor to change in third ventricle width. Atrophy over 1 and 2 years as indicated by enlargement of the third and lateral ventricle and shrinkage of the corpus callosum was greater for patients entering the trial with enhancing lesions. Greater disability increments over 1 and 2 years were associated with more severe third ventricle enlargement. CONCLUSION: In patients with relapsing MS and only mild to moderate disability, significant cerebral atrophy is already developing that can be measured over periods of only 1 to 2 years. The course of cerebral atrophy in MS appears to be influenced by prior inflammatory disease activity as indicated by the presence of enhancing lesions. Brain atrophy measures are important markers of MS disease progression because they likely reflect destructive and irreversible pathologic processes.