D. Ferriby

Neurologic manifestations in primary Sjögren syndrome: a study of 82 patients.

Abstract: Neurologic involvement occurs in approximately 20% of patients with primary Sjögren syndrome (SS). However, the diagnosis of SS with neurologic involvement is sometimes difficult, and central nervous system (CNS) manifestations have been described rarely. We conducted the current study to describe the clinical and laboratory features of SS patients with neurologic manifestations and to report their clinical outcome. We retrospectively studied 82 patients (65 women and 17 men) with neurologic manifestations associated with primary SS, as defined by the 2002 American-European criteria. The mean age at neurologic onset was 53 years. Neurologic involvement frequently preceded the diagnosis of SS (81% of patients). Fifty-six patients had CNS disorders, which were mostly focal or multifocal. Twenty-nine patients had spinal cord involvement (acute myelopathy [n = 12], chronic myelopathy [n = 16], or motor neuron disease [n = 1]). Thirty-three patients had brain involvement and 13 patients had optic neuropathy. The disease mimicked relapsing-remitting multiple sclerosis (MS) in 10 patients and primary progressive MS in 13 patients. We also recorded diffuse CNS symptoms: some of the patients presented seizures (n = 7), cognitive dysfunction (n = 9), and encephalopathy (n = 2). Fifty-one patients had peripheral nervous system involvement (PNS). Symmetric axonal sensorimotor polyneuropathy with a predominance of sensory symptoms or pure sensory neuropathy occurred most frequently (n = 28), followed by cranial nerve involvement affecting trigeminal, facial, or cochlear nerves (n = 16). Multiple mononeuropathy (n = 7), myositis (n = 2), and polyradiculoneuropathy (n = 1) were also observed. Thirty percent of patients (all with CNS involvement) had oligoclonal bands. Visual evoked potentials were abnormal in 61% of the patients tested. Fifty-eight patients had magnetic resonance imaging (MRI) of the brain. Of these, 70% presented white matter lesions and 40% met the radiologic criteria for MS. Thirty-nine patients had a spinal cord MRI. Abnormalities were observed only in patients with spinal cord involvement. Among the 29 patients with myelopathy, 75% had T2-weighted hyperintensities. Patients with PNS manifestations had frequent extraglandular complications of SS. Anti-Ro/SSA or anti-La/SSB antibodies were detected in 21% of patients at the diagnosis of SS and in 43% of patients during the follow-up (mean follow-up, 10 yr). Biologic abnormalities were more frequently observed in patients with PNS involvement than in those with CNS involvement (p < 0.01). Fifty-two percent of patients had severe disability, and were more likely to have CNS involvement than PNS involvement (p < 0.001). Treatment by cyclophosphamide allowed a partial recovery or stabilization in patients with myelopathy (92%) or multiple mononeuropathy (100%). The current study underlines the diversity of neurologic complications of SS. The frequency of neurologic manifestations revealing SS and of negative biologic features, especially in the event of CNS involvement, could explain why SS is frequently misdiagnosed. Screening for SS should be systematically performed in cases of acute or chronic myelopathy, axonal sensorimotor neuropathy, or cranial nerve involvement. The outcome is frequently severe, especially in patients with CNS involvement. Our study also underlines the efficacy of cyclophosphamide in myelopathy and multiple neuropathy occurring during SS.

Devic's neuromyelitis optica: clinical, laboratory, MRI and outcome profile

Devics neuromyelitis optica (NMO) associates optic neuritis and myelitis without any other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS), optic neuritis and myelitis being the inaugural symptom in 20% and 5% of MS cases, respectively. The aim of our study was to compare a new NMO cohort with recent studies and to try to determine the place of NMO in the spectrum of MS. We retrospectively studied 13 patients with a complete diagnostic workup for NMO. We compared our data with the most recent studies on NMO and with the criteria proposed by Wingerchuck et al. [Neurology 53 (1999) 1107]. We also determined whether these patients fulfilled the diagnostic criteria for MS. Thirteen patients (10 women and three men, with a mean age of 37.4 years) were included in the study. We found similar results to previously published data, except for an association with vasculitis in 38% of our cases. All but three of the patients fulfilled the clinical criteria for MS and two patients fulfilled both clinical and MRI criteria for MS. However, if we applied more restrictive criteria concerning spinal cord and brain MRI and CSF, none of our NMO patients fulfilled the MS diagnostic criteria. NMO might therefore be differentiated from MS by the application of more stringent criteria. Furthermore, all NMO patients should be investigated for vasculitis, even those with no history of systemic disease.

Is Devic's neuromyelitis optica a separate disease? A comparative study with multiple sclerosis.

Devics neuromyelitis optica (NMO) associates optic neuritis and myelopathy without other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS). However, there have been no previous studies comparing these two patho logies and it is still unclear if NMO is a separate entity or a subtype of MS. In the present study, we compared a series of NMO patients with a series of MS patients for whom optic neuritis or myelopathy was the presenting symptom, in order to determine the place of NMO in the spectrum of MS. We retrospectively studied 30 patients diagnosed with NMO and we compared these patients with 50 consecutive MS cases revealed by optic neuritis or acute myelopathy. MS patients were only included if a relapse occurred demonstrating time and space dissemination. We compared the two groups in terms of clinical presentatio n, laboratory findings (MRI and C SF) and clinical outcome. NMO patients were older and more frequently women than MS patients but the difference was not significant. C SF and MRI data were clearly different: oligoclonal bands (O C B) were found in 23% of NMO cases and 88% of MS (P B/0.001), abnormal brain MRI data were observed in 10% of NMO cases and 66% of MS (P B/0.001) and a large spinal cord lesion was observed in 67% of NMO cases and 7.4% of MS cases (P B/0.001). C linical outcome was evaluated as more severe in the NMO group (P B/0.001). O n the basis of clinical data, all NMO patients but three had dissemination in time and space. When we included MRI parameters, only two of the NMO patients met criteria for MS and one of the MS patients met criteria for NMO. O ur study demonstrates that NMO and MS should be considered as two different entities. The respective criteria for NMO and MS were able to distinguish these two patho logies but only when MRI data were applied. This finding could have implications for future therapeutic trials.

Long-term follow-up of neurosarcoidosis.

The authors evaluated the long-term clinical outcome of neurosarcoidosis and determined predictive factors of disease course. Twenty-seven patients with neurosarcoidosis were followed for at least 5 years from the onset of neurologic symptoms. Patients with CNS involvement during the course of the disease had a higher Modified Oxford Handicap Scale score than those with peripheral nervous system involvement (p < 0.02). CNS involvement may be a predictive factor for a less favorable disease course. Early and intensive treatment should be considered in such cases.

Intravenous corticosteroids in the postpartum period for reduction of acute exacerbations in multiple sclerosis.

In order to assess the effectiveness of monthly intravenous corticosteroids in reducing childbirth-associated acute exacerbations in multiple sclerosis (MS), we compared pregnant patients followed up in our MS clinic. During the first period (1996-1998), 22 patients did not receive any treatment after delivery. During the second period (1999-2001), following the publication of the PRIMS study, 20 patients were treated monthly with 1 g of intravenous corticosteroids during the six months of the postpartum period. In both groups the relapse rate increased during the first trimester postpartum but it was higher in the untreated group (2±0.66 [mean±SD]) compared with the treated group (0.8±0.41) (P=0.018), suggesting a beneficial effect of monthly intravenous corticosteroids.

Multiple sclerosis and depression: influence of interferon b therapy

Background and objectives: Depression is frequently part of the clinical picture of multiple sclerosis (MS). Major depression affects one in two patients with MS during the course of their lifetime. O ur objectives were to determine first, whether interferon b-1a (IFNb-1a) treatment increases the risk or level of depression and, secondly, whether depression status and depression evolution are related to the clinical characteristics of the disease. Patients and methods: We investigated 106 consecutive patients with relapsing-remitting MS treated with IFNb-1a (Avonex®). Patients with evidence of severe depression were excluded. The depression status, scored on the Beck Depression Inventory (BDI-II) (stratified as minimum, mild, moderate or severe level), and disability, scored on the Expanded Disability Status Scale (EDSS), were evaluated before and after 12 months of IFNb-1a treatment. Results: At baseline, 85% of patients had a minimum or a mild depression status and after 12 months of treatment most of them (83%) retained their baseline status. Beck scores before and after treatment were not significantly different (P =0.63). There was no correlation between age, gender, duration of illness or EDSS score and Beck score at baseline (P =0.696). Patients with disability progression after one year of IFNb-1a treatment had a significantly higher Beck score at baseline than patients without disability progression (P =0.003). Conclusion: IFNb-1a (Avonex®) does not seem to significantly influence the depression status of MS patients even in those with disability progression.

CSF isoelectrofocusing in a large cohort of MS and other neurological diseases.

The present study was performed in order to confirm the diagnostic value of isoelectrofocusing (IEF) in a large multiple sclerosis (MS) cohort and to evaluate the various neurological diseases probably to present a similar IEF profile. The cerebrospinal fluid (CSF) of 1292 patients with neurological diseases was studied by IEF. After a follow‐up of 2–36 months, we only included patients with a definite MS or confirmed diagnosis of other neurological diseases (OND). MS was diagnosed in 407 patients and OND in 593 patients. For patients in whom three or more oligoclonal bands (OCB) were detected, IEF results showed a sensitivity of 85% and a specificity of 92% for the diagnosis of MS. The positive and negative predictive values were 86.5 and 90%, respectively. Inflammatory and infectious disorders of the central nervous system represented the main affections associated with OCB, including human immunodeficiency virus encephalitis, Lyme disease and less frequently Sjogren syndrome. Furthermore, when OCB were observed, 10 or more bands were more frequently found in MS than in OND (P < 0.0001). IEF of the CSF is a reliable method for the diagnosis of MS. The absolute number of bands may help to discriminate between MS and OND.

Prospective study of patients presenting with acute partial transverse myelopathy.

Abstract.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.

Optical Coherence Tomography in Clinically Isolated Syndrome: No Evidence of Subclinical Retinal Axonal Loss

BACKGROUND Optical coherence tomography has emerged as a new tool for quantifying axonal loss in multiple sclerosis (MS). A reduction in retinal nerve fiber layer (RNFL) thickness is correlated with Expanded Disability Status Scale score and brain atrophy. OBJECTIVE To investigate RNFL and macular volume measurements using optical coherence tomography in the clinically isolated syndrome population. DESIGN Prospective case series. Settings Neurologic clinics at the university hospitals of Lille and Strasbourg (France). PARTICIPANTS Fifty-six consecutive patients with clinically isolated syndrome (18 with optic neuritis and 38 without optic neuritis) and 32 control subjects. MAIN OUTCOME MEASURES Macular volume and RNFL thickness. RESULTS Mean (SD) overall RNFL thickness (98.98 [10.26] microm) and macular volume (6.86 [0.32] microm(3)) in the clinically isolated syndrome population were not significantly different compared with the controls (98.71 [9.08] mum and 6.92 [0.38] microm(3), respectively). No link was noted between atrophy of the RNFL or macula and conversion to MS at 6 months. CONCLUSIONS Optical coherence tomography does not reveal retinal axonal loss at the earliest clinical stage of MS and does not predict conversion to MS at 6 months.

Combination of IFNβ‐1a (Avonex®) and mycophenolate mofetil (Cellcept®) in multiple sclerosis

To determine the safety of a combination of mycophenolate mofetil (Cellcept®, MMF) and IFNβ‐1a (Avonex®) in relapsing‐remitting multiple sclerosis (RRMS) and to evaluate the effects of the combination on clinical and magnetic resonance imaging (MRI) measures of disease activity. Secondary objectives were clinical and MRI data. An open‐label, single‐centre study including 30 RRMS patients was performed. Inclusion criteria were patients expanded disability status scale (EDSS) score <6.0, treated by Avonex® for at least 6 months, with at least two relapses during the previous 2 years and at least one during the previous 6 months. MMF at a progressive dose of 2 g per day orally was added to Avonex® for a duration of 6 months. MRI data were obtained at baseline and at the end of the study. The pre‐study annual relapse rate was 2.0 ± 0.7 and the EDSS score at baseline was 2.9 ± 1.3. Eleven patients had gadolinium (Gd)‐enhanced lesions at baseline for a total number of 35 lesions. Two patients interrupted the combination, one after the first dose for personal reasons unrelated to the study and the other due to diarrhoea. A few of the patients also reported nausea and abdominal pains. Adverse events included benign infectious diseases, insomnia and dizziness. No significant biological abnormalities were noted. The annualized relapse rate was 0.57 ± 0.3 at the end of the study (P < 0.001). The mean EDSS score was 2.6 ± 1.5 and no Gd‐enhanced lesions were detected on MRI at the end of the study. MMF and IFNβ‐1a (Avonex®) combined therapy is safe and very well‐tolerated. Clinical and MRI data suggest that this combination may be beneficial.