Secondary progressive multiple sclerosis: A national consensus paper on diagnostic criteria.

BACKGROUND: In clinical practice, the diagnosis of secondary progressive multiple sclerosis (SPMS) is often delayed, retrospective and non-reproducible, as there are no consensus criteria that define the advent of SPMS. Early identification of SPMS is essential to improve patient care. METHODS: Eight regional board meetings in France involving 56 multiple sclerosis (MS) experts (neurologists) were convened to discuss diagnostic criteria for SPMS. Subsequently, a national board meeting of 13 neurologists (with an expert representing each geographical region) was held to review points of convergence or divergence between regions and to develop a national consensus document. RESULTS: Based on the discussions from the regional boards, the MS experts at the national board retained the worsening of the EDSS score, with compatible clinical features, as the only consensus criterion for the diagnosis of SPMS in clinical practice. The patient should have experienced during at least the previous 6 months and in the absence of any relapse, a worsening in the EDSS score of +1.0 point (if the previous EDSS was≤5.0) or of +0.5 point (if the previous EDSS was≥5.5), with a pyramidal or cerebellar functional system score≥2 and without setting a minimum EDSS score; or, in case of a stable EDSS score≥4.0, a worsening of a functional score. This worsening should be confirmed within 3 to 6 months. According to the MS experts, the patient's age, duration of illness and a minimal threshold EDSS score are only risk factors for transition to SPMS. Patient reports during consultation and cognitive impairment are important warning signs, which should trigger an objective assessment with specific tests or closer monitoring. Clinical relapse and/or MRI activities are non-discriminatory for making the diagnosis of SPMS. CONCLUSIONS: The experts defined precise diagnostic criteria adapted to clinical practice for earlier identification of SPMS, paving the way for better management of this stage of the disease.

MSCopilot, a new multiple sclerosis self-assessment digital solution: results of a comparative study versus standard tests.

BACKGROUND AND PURPOSE: Assessing patients' disability in multiple sclerosis (MS) requires time-consuming batteries of hospital tests. MSCopilot is a software medical device for the self-assessment of patients with MS (PwMS), combining four tests: walking, dexterity, cognition and low contrast vision. The objective was to validate MSCopilot versus the Multiple Sclerosis Functional Composite (MSFC). METHODS: This multicentre, open-label, randomized, controlled, crossover study enrolled 141 PwMS and 76 healthy controls (HCs). All participants performed MSCopilot and MSFC tests at day 0. To assess reproducibility, 46 PwMS performed the same tests at day 30 ± 3. The primary end-point was the validation of MSCopilot versus MSFC for the identification of PwMS against HCs, quantified using the area under the curve (AUC). The main secondary end-point was the correlation of MSCopilot z-scores with MSFC z-scores. RESULTS: In all, 116 PwMS and 69 HCs were analysed. The primary end-point was achieved: MSCopilot performance was non-inferior to that of MSFC (AUC 0.92 and 0.89 respectively; P = 0.3). MSCopilot and MSFC discriminated PwMS and HCs with 81% and 76% sensitivity and 82% and 88% specificity respectively. Digital and standard test scores were highly correlated (r = 0.81; P < 0.001). The test-retest study demonstrated the good reproducibility of MSCopilot. CONCLUSION: This study confirms the reliability of MSCopilot and its usability in clinical practice for the monitoring of MS-related disability.

A prospective observational post-marketing study of natalizumab-treated multiple sclerosis patients: clinical, radiological and biological features and adverse events. The BIONAT cohort.

BACKGROUND AND PURPOSE: BIONAT is a French multicentric phase IV study of natalizumab (NTZ)-treated relapsing-remitting multiple sclerosis (MS) patients. The purpose of this study was to collect clinical, radiological and biological data on 1204 patients starting NTZ, and to evaluate the clinical/radiological response to NTZ after 2 years of treatment. METHODS: Patients starting NTZ at 18 French MS centres since June 2007 were included. Good response to NTZ was defined by the absence of clinical and radiological activity. Data analysed in this first report on the BIONAT study focus on patients who started NTZ at least 2 years ago (n = 793; BIONAT2Y ). RESULTS: NTZ was discontinued in 17.78% of BIONAT2Y. The proportion of patients without combined disease activity was 45.59% during the first two successive years of treatment. Systematic dosage of anti-NTZantibodies (Abs) detected only two supplementary patients with anti-NTZ Abs compared with strict application of recommendations. A significant decrease of IgG,M concentrations at 2 years of treatment was found. CONCLUSIONS: The efficacy of NTZ therapy on relapsing-remitting MS in a real life setting is confirmed in the BIONAT cohort. The next step will be the identification of biomarkers predicting response to NTZ therapy and adverse events.

Progressive neuropsychiatric manifestations of phenylketonuria in adulthood.

INTRODUCTION: Neuropsychiatric signs and MRI abnormalities can occur in patients with phenylketonuria in adulthood. We describe clinical and radiological features of phenylketonuric patients and we discuss the advantage of continuing diet in adulthood. METHOD: We report late onset neuropsychiatric symptoms of four phenylketonuric patients (33-45years) diagnosed in infancy and report the case of a patient (33years) diagnosed with phenylketonuria because of late onset neurological signs. We describe clinical and radiological features of these 5 patients, and their evolution under diet and propose a review of the literature. RESULTS: The main neurological abnormalities in phenylketonuric patients diagnosed in infancy are: brisk reflexes, spastic paraparesis, psychiatric signs that appear 10.5years after the diet arrest. A leukoencephalopathy was present in 93% of cases and 91.7% improve clinically after poor phenylalanine diet reintroduction. In 4 patients, neurological abnormalities (spastic paraparesis, dementia, Parkinsonism) led to the late diagnosis. Two of them had a leukoencephalopathy on brain MRI. Patients had high levels of phenylalanine (above 1500µmol/L) when neuropsychiatric signs occurred. Improvement after diet suggests that hyperphenylalaninemia has a direct toxic effect on the brain. DISCUSSION/CONCLUSION: The long-term follow-up of phenylketonuric patients is mandatory to depict and treat neurological complications in time. Diet reintroduction is efficacious in most cases.

Acute disseminated encephalomyelitis in two renal transplant patients: is there a role for Epstein-Barr virus reactivation?

Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disease of the central nervous system, usually occurring after a vaccination or infectious disease. It has been exceptionally described in transplanted patients. The pathophysiology remains incompletely understood. We report the clinical, biological and magnetic resonance imaging (MRI) presentation and evolution of two kidney-transplanted patients with ADEM associated with local Epstein-Barr virus (EBV) reactivation. ADEM may occur in transplanted patients with favorable evolution. Its pathophysiology is uncertain, and the implication of EBV is discussed.

LSN MS guidelines for the management of multiple sclerosis.

OBJECTIVE: The prevalence of multiple sclerosis (MS) in Lebanon is unknown, as there are no available or reliable epidemiological studies to date. The circumstances of Middle East countries are different from those of Europe and North America in terms of differential diagnoses and disease management. The aim of the conference is to establish guidelines for diagnosis, treatment, follow-up and management of patients with MS in Lebanon. Another objective is to discuss and participate in research projects based on epidemiology, clinical trials and more fundamental aspects of the disease in the future. METHODS: Under the authority of the Lebanese Society of Neurology (LSN), a group of neurologists took the initiative to participate in this LSN MS committee with the purpose of establishing a consensus for the management of patients with MS, and under the supervision of a Coordinator (A.T.) designed by the LSN board. RESULTS: Diagnostic and therapeutic, follow-up and research recommendations were proposed with special emphasis on the specific needs and circumstances of Lebanon. The experts highlighted the importance of considering particular needs, the identification of patients at high risk of developing MS in order to maximize therapeutic opportunities, and cost-effective control of treatment efficacy, as well as global assessment of disability. CONCLUSIONS: The experts established guidelines concerning diagnosis, treatment, and follow-up of patients with MS in Lebanon. Furthermore, they recommended some clinical and fundamental research projects.

Severe multiple sclerosis reactivation under fingolimod 3 months after natalizumab withdrawal.

We report the case of a woman with multiple sclerosis who developed a severe neurological condition following natalizumab (NZB) withdrawal and soon after fingolimod (FTY) initiation. FTY was started 3.5 months after a two-year NZB treatment. Fifteen days later, she suffered partial repetitive seizures followed by a tonicoclonic seizure. This was associated with attention difficulties and an increased asthenia. Brain MRI follow-up disclosed large demyelinating active lesions in favour of disease reactivation. This case suggests that FTY introduction may occur less than three months after NZB withdrawal.

Contribution of imaging to the diagnosis of optic neuropathies.

Magnetic resonance imaging is the modality of choice to investigate patients with central nervous system diseases. In patients with optic neuritis, early MRI allows positive and differential diagnosis, and gives arguments for prognosis. The technique should be adapted for the exploration of visual pathways. Inflammatory optic neuritis is characterized by an early signal abnormality within the optic nerve, whereas optic nerve MRI is normal in the early phase of ischemic optic neuropathy. MRI also detects compressive and infiltrative lesions. Meningiomas are characterized by abnormalities within the peri-optical spaces, whereas a global increase in the size of the optic nerve is in favor of a glioma.

Health related quality of life and perceived social support in French and Lebanese MS patients: A comparative study.

BACKGROUND: The perception of diagnosis announcement, the social support and the coping strategies seem to be determining factors for the quality of life of multiple sclerosis (MS) patients, with possible transcultural variations. This study explores these psychosocial dimensions in Lebanese and French MS patients. METHODS: For this cross-sectional multi-center study, 8 questionnaires were used to assess quality of life, family support, coping strategies, mood, fatigue, stress, and hopelessness in MS patients. 7 were translated into Arabic and then back translated into French. These were administered to a group of Lebanese MS patients and compared to an MS sample from France. The data was collected for both populations and analyzed. RESULTS: A total of 107 patients were included, 46 Lebanese and 61 French. The majority of MS patients were young females with a high level of education, relapsing remitting form of MS and a low level of disability. Both populations exhibited comparable quality of life and answers on the questionnaires regarding mood disorders, hopelessness, and perceived stress. However, the French patients had significantly more fatigue. Perceived social support given by family was considered greater in the French group compared to the Lebanese one. Also, maladaptive coping strategies (such as self-distraction, denial, behavioral disengagement, substance use, self-blame, venting) were used more frequently by the French population compared to the Lebanese, and this correlated with higher anxiety scores. Diagnosis communication was overall brief, informative, and satisfying in both populations. CONCLUSION: This study highlighted transcultural differences between French and Lebanese MS patients mainly in social support and coping strategies.

Dramatic worsening following plasma exchange in severe post-natalizumab withdrawal multiple sclerosis relapse.

We report the case of a young woman with multiple sclerosis who discontinued natalizumab twice and experienced a severe relapse following each natalizumab withdrawal. The first relapse was successfully treated by intravenous methylprednisolone (IVMP). In contrast the second relapse was unresponsive to IVMP. Subsequent treatment by plasma exchanges (PLEX) was followed by a dramatic neurological worsening. This case suggests that PLEX after natalizumab discontinuation may increase relapse severity.

[MRI in diagnosis and follow-up of patients with adult metabolic disease: contribution of new techniques]. / Place de l'IRM dans l'orientation diagnostique et le suivi des maladies métaboliques: intérêt des nouvelles techniques.

INTRODUCTION: Conventional MRI allows diagnostic and prognosis approaches for patients with suspected metabolic disease. BACKGROUND: Bilateral and symmetrical abnormalities are the most suggestive aspects. Signal characteristics (intensity, difference of signal on various sequences), lesion extension and location provide important etiological information. Non-conventional MRI techniques are particularly interesting for pathophysiology. Different MRI modalities offer promising techniques for monitoring treatments and patient follow-up. CONCLUSION: Combining different MRI modalities can contribute to the diagnosis and help improve understanding of the pathogenic mechanisms of adult metabolic diseases; they offer promising options for the prognosis and treatment follow-up.

[NeuroBehcet disease with corpus callosum involvement]. / Neuro-Behçet avec atteinte du corps calleux.

INTRODUCTION: Behçet's disease is a multi-system vascular-inflammatory disease with possible involvement of the central nervous system. Lesions of the corpus callosum on MRI have been rarely reported in this disease. CASE REPORT: A 47-year-old woman was admitted for a sudden right hemiplegia and confusion revealing a Behcet's disease. MRI showed a pedonculo-thalamic lesion and a white matter hypersignals, which was suggestive of the disease. Besides, involvement of the corpus callosum was observed. CONCLUSION: This case demonstrates that Behcet's disease should be considered among diseases with corpus callosum involvement.

Leukoencephalopathies associated with inborn errors of metabolism in adults.

The discovery of a leukoencephalopathy is a frequent situation in neurological practice and the diagnostic approach is often difficult given the numerous possible aetiologies, which include multiple acquired causes and genetic diseases including inborn errors of metabolism (IEMs). It is now clear that IEMs can have their clinical onset from early infancy until late adulthood. These diseases are particularly important to recognize because specific treatments often exist. In this review, illustrated by personal observations, we give an overview of late-onset leukoencephalopathies caused by IEMs.

[Myelin and nuclear magnetic resonance]. / Myéline et résonance magnétique nucléaire.

MRI is one of the most important tools for the investigation of white matter diseases of the central nervous system. Other techniques based on the magnetic resonance phenomena (magnetization transfer imaging, diffusion imaging, magnetic resonance spectroscopy) have joined MRI to better caracterize certain diseases, understand their pathophysiology and follow their evolution.

[Subtle brain abnormalities in adrenomyeloneuropathy]. / Anomalies cérébrales subtiles de l'Adrénomyéloneuropathie.

PURPOSE: To describe subtle brain abnormalities detected on MRI in adult patients with adrenomyeloneuropathy (AMN). Materials and methods. Retrospective evaluation of data acquired prospectively as part of a clinical trial (Riluzole) in 66 adult patients with AMN without obvious brain lesion on MR. All patients underwent brain MR including T1W, T2W, FLAIR and spectroscopy. After a review had been validated by three different reviewers, review of MR images was performed by consensus using a semi-quantitative scale. RESULTS: Preliminary analysis of MR images confirmed the presence of signal abnormalities involving the corticospinal tracts in 36 patients (54.6%). Additional subtle abnormalities were also detected: white matter palor, mainly parieto-occipital in location, with patchy hyperintensity in 36 patients (54.6%), hyperintense pontocerebellar fibers on T2W and FLAIR in 25 patients (41.7%). The presence of elevated Cho/Cr and mI/Cr ratios, described in the literature, were confirmed. CONCLUSION: This retrospective study allows the description of an AMN pattern on MRI in patients without white matter or callosal abnormalities.

Theoretical modeling of time-dependent skin temperature and heat losses during whole-body cryotherapy: A pilot study.

This article establishes the basics of a theoretical model for the constitutive law that describes the skin temperature and thermolysis heat losses undergone by a subject during a session of whole-body cryotherapy (WBC). This study focuses on the few minutes during which the human body is subjected to a thermal shock. The relationship between skin temperature and thermolysis heat losses during this period is still unknown and have not yet been studied in the context of the whole human body. The analytical approach here is based on the hypothesis that the skin thermal shock during a WBC session can be thermally modelled by the sum of both radiative and free convective heat transfer functions. The validation of this scientific approach and the derivation of temporal evolution thermal laws, both on skin temperature and dissipated thermal power during the thermal shock open many avenues of large scale studies with the aim of proposing individualized cryotherapy protocols as well as protocols intended for target populations. Furthermore, this study shows quantitatively the substantial imbalance between human metabolism and thermolysis during WBC, the explanation of which remains an open question.

[Isolated ptosis in a 58-year-old woman]. / Ptosis isolé apparu chez une femme à l'âge de 58 ans.

A 60-year-old woman who had experienced isolated ptosis for two years was seen when it had been fixed for one year. She had a personal and familial history of stromal corneal dystrophy. The diagnosis of mitochondrial cytopathy was made on the basis of clinical, electrophysiological, biological and histological findings. Surgical repair of the ptosis allowed visual recovery. The relationship between ptosis, corneal dystrophy and mitochondrial cytopathy is discussed.