Focal cortical atrophy following transient meningeal enhancement in a progressive multiple sclerosis.

Recent studies identified chronic leptomeningeal enhancement (LME) in late-acquired FLAIR sequences in secondary progressive (SP) multiple sclerosis (MS). These LMEs correlate with focal cortical inflammation and demyelination observed by pathology, which are supposed to drive long-term cortical atrophy. We report a spontaneously remitting meningeal uptake in a patient suffering from SP MS. No cortical lesion was visible on FLAIR or DIR sequences, but the rate of cortical atrophy was higher in this area. This case suggests that conventional 3-T MRI, by contrary to white matter lesions, may be amnesic with regard to the potential burden of previous regressive meningeal lesions. Moreover, T1-enhanced sequences underscore the real inflammatory activity. LME could be more than passive markers of SP MS, but is also directly responsible for focal cortical atrophy and could be an early manifestation of cortical lesions.

Paraneoplastic neuromyelitis optica and ovarian teratoma: A case series.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare inflammatory disease of the central nervous system, characterized by the presence of auto-antibodies directed against aquaporin-4 (AQP4) expressed on astrocyte end-feet. Despite NMOSD does not primarily belong to the spectrum of paraneoplastic neurological syndromes, rare cases of association with neoplasia have been outlined. Here, we report the association of NMOSD with ovarian teratoma in 3 cases. Pathological analysis of teratomas revealed glial component strongly expressing AQP4 and closely localized to immune infiltrates. Our series highlight the rare association of teratoma with NMOSD and the possible paraneoplastic mechanism.

Estimation of intrathecal IgG synthesis: simulation of the risk of underestimation.

OBJECTIVE: The low level of passively diffused IgG through the blood-brain barrier is sufficient to blur the estimation of intrathecal IgG synthesis (ITS). Therefore, this estimation requires a mathematical calculation derived from empirical laws, but the range of normal values in healthy controls is wide enough to prevent a precise calculation. This study investigated the precision of various methods of ITS estimations and their application to two clinical situations: plasma exchange and immune suppression targeting ITS. METHODS: Based on a mathematical model of ITS, we constructed a population of healthy controls and applied a tunable ITS. RESULTS: We demonstrate the following results: underestimation of ITS is common at individual level but true ITS is well fitted by cohorts; Q IgG increases after plasma exchange; IgG Loc calculation based on Qlim falsely increases when Q Alb decreases; the sample size required to demonstrate a decrease in ITS increases exponentially with larger Q Alb. INTERPRETATION: Studies evaluating changes in ITS level should be adjusted to Q Alb. Low amounts of ITS could be largely underestimated.

No evidence of disease activity (NEDA) in MS should include CSF biology - Towards a 'Disease-Free Status Score'.

The concept of NEDA (no evidence of disease activity) was forged to describe relapse-free patients under treatment with recent drugs, but this goal is reached by less than half of all patients and not sustained over time. However a complete remission of disease is expected to be associated with the normalization of CSF biomarkers. On pathophysiological grounds, we propose to add the criterion of no evidence of biological activity in CSF to design a future 'disease-free status score'. This composite criterion, which should concern neurodegenerative and immune activation biomarkers, would be better suited for assessing the persistence of biological processes long before CNS atrophy occurs and should help in predicting long-term remission/progression of MS.

Compartmentalized intrathecal immunoglobulin synthesis during HIV infection - a model of chronic CNS inflammation?

HIV infects the central nervous system (CNS) during primary infection and persists in resident macrophages. CNS infection initiates a strong local immune response that fails to control the virus but is responsible for by-stander lesions involved in neurocognitive disorders. Although highly active anti-retroviral therapy now offers an almost complete control of CNS viral proliferation, low-grade CNS inflammation persists. This review focuses on HIV-induced intrathecal immunoglobulin (Ig) synthesis. Intrathecal Ig synthesis early occurs in more than three-quarters of patients in response to viral infection of the CNS and persists throughout the course of the disease. Viral antigens are targeted but this specific response accounts for <5% of the whole intrathecal synthesis. Although the nature and mechanisms leading to non-specific synthesis are unknown, this prominent proportion is comparable to that observed in various CNS viral infections. Cerebrospinal fluid-floating antibody-secreting cells account for a minority of the whole synthesis, which mainly takes place in perivascular inflammatory infiltrates of the CNS parenchyma. B-cell traffic and lineage across the blood-brain-barrier have not yet been described. We review common technical pitfalls and update the pending questions in the field. Moreover, since HIV infection is associated with an intrathecal chronic oligoclonal (and mostly non-specific) Ig synthesis and associates with low-grade axonal lesions, this could be an interesting model of the chronic intrathecal synthesis occurring during multiple sclerosis.

Natalizumab is effective in controlling the inflammatory rebound after its discontinuation and failure of an alternative treatment.

Progressive multifocal leukoencephalopathy (PML) is the most feared complication when natalizumab (NAT) is used in the treatment of relapsing multiple sclerosis (MS). JC virus serologic status is a currently established risk factor for PML. When seroconversion occurs, NAT discontinuation should be based on a solid rationale to avoid an MS inflammatory resurgence. The JC virus index value may also provide further useful information to help practitioners and patients in their decision process.

Neuropsychological syndromes in multiple sclerosis.

BACKGROUND: Cognitive impairment in multiple sclerosis (MS) is common (45-65%).Deficits occur in speed of information processing (SIP), memory, attention, executive functions (EF) and visuoconstruction.Involvement of cognitive functions like language and gnosis is rare and lesser known. Our aim is to describe the cognitive function and the clinical and radiological features of five patients with MS and with neuropsychological syndromes (NPS). METHOD: Retrospective review of MS patients with NPS studied, using specific tests of SIP, memory, attention, EF, visuo-spatial abilities, praxis and language. RESULTS: The sample included four women (3 relapsing-remitting MS/1 secondary progressive MS) and one man with primary progressive MS (aged between 30-55 years). Cognitive symptoms were the initial complaint in three cases. Three cases presented apperceptive agnosia and constructive apraxia, one case presented alexia with agraphia and the fifth patient presented motor aphasia. Four patients suffered cognitive dysfunction considered typical of MS. Magnetic resonance imaging (MR) in all cases showed high lesion volumes in T1 and T2-weighted sequences. A good correlation was observed between cognitive deficits and the location of the lesions in four patients. CONCLUSIONS: NPS may be the initial complaint in MS patients, often associated with other cognitive deficits, and it shows a close relationship with lesion location.