[Myelitis as a differential diagnosis of spinal cord tumors]. / Diagnostic différentiel des tumeurs intramédullaires : les myélites.

BACKGROUND AND PURPOSE: Myelitis is common, related to multiple aetiologies and constitute in some cases a differential diagnosis for spinal cord tumors. Our objective was to review the clinical and paraclinical aspects of the main aetiologies of myelitis. METHODS: These aetiologies will be reviewed based on data not only from the scientific literature but also from our personal experience reported in different cohorts of patients. RESULTS: Multiple sclerosis is the main cause of partial myelitis in young adults. Neuromyelitis optica is now a well-known specific entity frequently revealed by a transverse myelitis. The diagnosis is based on specific criteria, including the presence of anti-NMO antibodies. In our cohorts, approximately 12 % of the patients admitted for an acute or subacute myelitis were related to infections, mainly of a viral origin. Patients with myelitis must be screened for systemic diseases. As for neuromyelitis optica, patients with myelitis related to a systemic disease should be treated in emergency. Acute myelitis is sometimes the first symptom of a systemic lupus or of a sarcoidosis. Sjögren syndrome can mimic myelitis related to primary progressive multiple sclerosis. Spinal cord imaging contributes greatly to defining the myelitis. CONCLUSION: In most cases, a routine clinical and paraclinical examination and the follow-up of the patients can contribute to establishing the aetiology of a myelitis.

[Inaugural psychotic events in multiple sclerosis?]. / Evènements psychotiques inauguraux de sclérose en plaques?

INTRODUCTION: Psychotic symptoms are not readily recognized in multiple sclerosis, especially at the beginning of the disease. METHODS: We report the cases of four patients who developed psychotic symptoms that led to the diagnosis of multiple sclerosis. We describe the psychiatric and neurological features, MRI findings, clinical outcome and treatment. RESULTS: Two patients developed persecutory delusions, one presented a manic episode and the fourth melancholia with catatonia. Mean age was 39 years (range 20-49 years). Two patients had a personal history, but none a familial history of psychiatric disease. Examination of the cerebrospinal fluid revealed an oligoclonal pattern in all patients. All patients fulfilled Barkhof's MRI criteria. Three have had brain MRI with injection during psychotic symptoms. In these three cases, a frontal lesion appeared. The patient with catatonia also had a new lesion in the cerebellum and in the brainstem. All patients needed a "psychiatric" treatment, including antipsychotics. The psychiatric event lasted three months for two patients and the two others experienced relapse. CONCLUSION: Acute psychiatric symptom may reveal multiple sclerosis at the beginning of the disease. Frontal lobe localization is suggested. We propose that a psychotic event may correspond to a multiple sclerosis event.

[Cognitive impact of mitoxantrone and methylprednisolone in multiple sclerosis: an open label study]. / Impact cognitif d'un traitement associant mitoxantrone et méthylprednisolone dans la sclérose en plaques.

Interferons beta have shown some positive effects on cognitive function in multiple sclerosis (MS). The potential immunosuppressive impact of mitoxantrone on cognitive dysfunction in MS has never been evaluated. We assessed changes in cognitive dysfunction in patients with very active MS treated with mitoxantrone combined with methylprednisolone. We assessed a non randomized controlled trial including successively 15 consecutive MS patients. Very active MS was defined by a progression of at least two EDSS points or more than two relapses during the previous year and at least one enhanced lesion after gadolinium infusion on MRI. All patients received a monthly intravenous pulse of mitoxantrone (20mg) for six months with methylprednisolone (1g). Global cognitive efficiency, memory and executive function were assessed before treatment (M0) and after six months (M6) and 12 months (M12) of treatment. To evaluate the learning effect, 15 healthy subjects also participated. A significant improvement in global cognitive efficiency was observed at M6 and was sustained at M12, as a few parameters on memory and executive functions. We suggest that mitoxantrone combined with methylprednisolone has a potential positive effect on cognitive functions.

[Polymyositis and cranial neuropathy]. / Polymyosite et atteinte de nerfs crâniens.

BACKGROUND: Polymyositis with cranial neuropathy has been rarely reported. CASE REPORTS: We describe here three cases of polymyositis with trigeminal or facial neuropathy. Patients had muscular weakness, myalgia, rhabdomyolysis, endomysial infiltration with necrosis and regeneration at biopsy of muscle and, for two of them, a myopathic pattern at electromyogram. Two patients had also a Sjögren's syndrome and anti-nuclear antibodies. Anti-JO1 antibodies were presents in only one case. The outcome for one patient was good with corticosteroids alone. One other improved with the adjunction of immunoglobulin. The third one had a macrocheilia, a facial diplegia, antibodies against voltage-gated potassium channels and a neuromyotonia secondary to a paraneoplastic syndrome. He died after one year despite a treatment by corticosteroids and immunoglobulin. Patients fulfilled the diagnosis of polymyositis according to clinical, electromyographic, biological and histopathologic criteria. For the two patients with Sjögren's syndrome, the question of a primitive or a secondary Sjögren's syndrome remains unknown. CONCLUSION: The occurrence of a cranial neuropathy in polymyositis should make us looking for an association with paraneoplastic syndrome or connective tissue disease.

Combination of IFN beta-1a (Avonex) and mycophenolate mofetil (Cellcept) in multiple sclerosis.

To determine the safety of a combination of mycophenolate mofetil (Cellcept, MMF) and IFNbeta-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 IFNbeta-1a (Avonex) combined therapy is safe and very well-tolerated. Clinical and MRI data suggest that this combination may be beneficial.

A specific clinical pattern of camptocormia in Parkinson's disease.

BACKGROUND: Camptocormia, characterised by extreme forward flexion of the thoracolumbar spine and severe stooping in the supine position, seems to be prevalent in Parkinson's disease. OBJECTIVE: The aim of this study was to identify features of parkinsonian camptocormia and to describe the main clinical characteristics of patients with Parkinson's disease who develop the condition. METHODS: An extensive range of clinical, biochemical and imaging data were gathered for 23 patients with Parkinson's disease with camptocormia, notably including magnetic resonance imaging (MRI) of the brain and spine, electromyographic recordings of the paravertebral muscles and muscle biopsies. RESULTS: Camptocormia occurred in severe Parkinson's disease with axial predominance, motor fluctuations and dysautonomic symptoms. The condition was often associated with spondyloarthritic changes and pain. MRI showed paraspinal muscle signal abnormalities in five patients and fatty involution in seven patients. The seven patients had motor unit reductions on the spinal erector electromyogram. The MRI results for the girdle muscles were normal. Cranial MRI showed signal abnormalities for the basal ganglia in three patients. DISCUSSION: Various mechanisms may contribute to the development of parkinsonian camptocormia: dopaminergic depletion in Parkinson's disease induces functional changes in the organisation of the corticospinal and reticulospinal tracts, where dysfunction could contribute to axial rigidity. Furthermore, rigidity of the spinal flexion muscles could lead to under-use of the spinal extension muscles, which become progressively atrophic. Rigidity may also induce spinal deformations, leading to a neurogenic syndrome via compression of the spinal nerves. CONCLUSION: The screening and early management of camptocormia in Parkinson's disease is likely to be important for preventing axial disorders and spinal deformations.

A new case of autosomal dominant myotonia associated with the V1589M missense mutation in the muscle sodium channel gene and its phenotypic classification.

We report a phenotype associated with the Val1589Met substitution in SCN4A gene in a French family which would be better classified as paramyotonia congenita. The proband was a 48-year-old woman, who described muscle stiffness and occasional flaccid weakness, both symptoms being induced by exercise, cold and heat. Severe muscle stiffness affected facial, oropharyngeal and limb muscles leading to transient paralysis of these muscles. One sister, two nephews and the son of the proband had similar symptoms. Molecular analysis of the muscle sodium channel gene (SCN4A) by nucleotide sequencing revealed a G-to-A transition of cDNA nucleotide at position 4765 predicting a substitution of methionine for valine at position 1589. This shows that the Val1589Met mutation in the SCN4 gene may cause different phenotypes, either potassium-aggravated myotonia or paramyotonia congenita. Familial or individual factors other than the missense mutation per se influence the expression of the disease in sodium channel disorders.

One-year cyclophosphamide treatment combined with methylprednisolone improves cognitive dysfunction in progressive forms of multiple sclerosis.

We conducted an evaluation of changes in cognition in progressive multiple sclerosis (MS) patients receiving monthly intravenously pulse of cyclophosphamide (700 mg/m2) with methylprednisolone (1g). Twenty-eight consecutive progressive MS patients (10 primary progressive, 18 secondary progressive MS) were evaluated before and after six and 12 months of treatment. The WAIS-R score, memory and executive functions were evaluated. Under treatment we found a significant improvement in global cognitive efficiency, encoding abilities, planning abilities and inhibition after six and 12 months. However, mechanisms of action of the positive effect of these anti-inflammatory and immunosuppressive treatments on cognition remain unclear.

Brain MRI in late-onset multiple sclerosis.

Multiple sclerosis (MS) with clinical onset after 50 years of age is unusual (between 1 and 6%) and is frequently misdiagnosed. Furthermore, brain magnetic resonance imaging (MRI) abnormalities are frequently observed in subjects over 50 years of age. The aim of this study was to describe brain MRI in late-onset MS to evaluate the sensitivity and specificity of radiological MS criteria in patients aged over 50 years. We evaluated the brain MRI of 20 patients with onset of MS after 50 years of age. We compared these MRI with 26 controls matched for age, sex and vascular risk factors. MRI were blindly analysed by two neuroradiologists according to Paty et al.'s [Neurology38 (1988) 180] criteria, Fazekas et al.'s [Neurology38 (1988) 1822] criteria and Barkhof et al.'s [Brain120 (1997) 2059] criteria. The mean age at MRI scanning was 58 years. Sensitivity was 90% for Paty et al.'s criteria, 80% for Fazekas et al.'s criteria and 85% for Barkhof et al.'s criteria. Specificity was 54% for Paty et al.'s criteria, 69% for Fazekas et al.'s criteria and 65% for Barkhof et al.'s criteria. Barkhof et al.'s criteria are less specific in older patients than in young patients. We suggest that spinal cord MRI and cerebrospinal fluid analysis should be systematically performed in suspected late-onset MS in order to increase the specificity of the diagnosis.

[Infectious myelopathies: clinical, serological, and prognostic patterns]. / Myélopathies infectieuses: profils cliniques, paracliniques et évolutifs.

INTRODUCTION: Serological confirmation of an infectious acute myelitis injury is difficult to confirm as it is sometimes due to a post-infectious etiology. OBJECTIVES: The aim of this study was to define the clinical, biological and prognostic patterns of infectious myelitis. PATIENTS AND METHODS: This retrospective study included 153 subjects hospitalized in the department of neurology between 1993 and 2002 for treatment of a noncompressive acute myelopathy. Biological confirmation of recent infection was obtained in 12 patients (8 p. 100). RESULTS: An infectious syndrome, beginning prior to the neurological symptoms, was found in 67 percent of patients. The clinical symptoms were severe with loss of sensoromotor and sphincter functions and ascending spinal cord dysfunction (acute transverse myelopathy). Spinal cord MRI showed extended centromedullar high intensity signals with rapid and complete regression. CSF analysis cell count was above 30/mm3 with hyperproteinorachia, in 75 percent and 58 percent of patients respectively. CSF electrophoresis did not detect oligoclonal bands. Clinical outcome was good in all patients except one, however sphincter disorders recovered slowly. DISCUSSION: Our study illustrates a stereotypical clinical, biological and prognostic pattern for infectious acute myelitis. These findings contribute significantly to therapeutic decision making and establishing prognosis at the initial phase of acute myelopathy.

[Guillain-Barré syndrome with hallucinations and onirism: an underestimated association]. / Syndrome de Guillain-Barré et état oniroïde: une association sous-estimée?

INTRODUCTION: Guillain-Barré Syndrome (GBS) is generally related to peripheral nervous system involvement, but certain variants with central nervous system manifestations have been described. CASE REPORT: In the present study we report 2 patients with GBS associated with hallucinations and onirism. Two men (age 64 and 49 years) presented GBS without proven infectious origin who required intensive care because of respiratory problems. The disease progressed and manifestations of encephalitis (hallucinations and onirism) appeared. The sensorimotor signs and encephalitis manifestations evolved in parallel with full recovery in the first patient and death after 11 months of intensive care in the second. CONCLUSION: GBS may be associated with stereotypic central nervous system symptoms, mimicking delirium tremens. The manifestations would be related to the severity of the initial period, but not to long-term prognosis.

[Pure subacute pandysautonomia: an assessment of treatment with intravenous polyvalent immunoglobulins]. / Pandysautonomie isolée subaiguë: intérêt du traitement par immunoglobulines polyvalentes.

INTRODUCTION: Acute or sub-acute pure dysautonomia is uncommon. We report a case of sub-acute pure pandysautonomia with favorable outcome after intravenous immunoglobulin therapy. CASE REPORT: A 29-year-old right-handed student, with an uneventful medical history presented, for one month, bilateral loss of visual acuity and digestive disorders, associating diarrhea, vomiting and anorexia. Physical examination revealed bilateral intrinsec oculomotor nerve palsy, a dryness syndrome and severe orthostatic hypotension. Ophthalmologic examination showed bilateral diffuse parasympathic impairment associating an Argyll Robertson pupil and full pupil light reflex abolition. Elevated protein level (0.93g/l) was the only cerebrospinal fluid anomaly. Serum tests were negative for anti-gangliosides antibodies. The patient improved slowly after two series of intravenous immunoglobulin infusions. CONCLUSION: Clinical course and laboratory findings suggest that acute or sub-acute pure pandysautonomia events are likely to be related to acute polyradiculoneuritis. Therefore intravenous polyvalent immunoglobulin infusions should be attempted, even if their efficacy needs to be confirmed.

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.

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.

[Neuromeningeal tuberculosis: the contribution of genetic amplification to diagnosis]. / Tuberculose neuro-méningée: apport de la méthode par amplification génique dans le diagnostic.

Neurological manifestations of tuberculosis are rare, especially in immunocompetent subjects. The heterogeneity of clinical and radiological features induces frequently a delay for diagnosis. The aim of the study was to describe clinical and radiological presentation of 11 cases of neuro-tuberculosis and to evaluate clinical outcome. We performed clinical, CSF, MRI and outcome evaluation in all patients. We also performed a mycobacterium analysis by polymerase chain reaction (PCR). Patients were 6 men and 5 women with a mean age of 45.4 years. Clinical presentations were meningeal symptoms in 9 cases and focal manifestations in 4 cases. CSF was abnormal in 82 p.cent of cases (protein increase in 73 p.cent, pleiocytosis in 73 p.cent, hypoglycorrhachia in 45 p.cent and hypochlorrhachia in 36 p.cent). The best diagnostic test was PCR (positive in 45 p.cent of cases). CSF cultures were positive in only 2 cases (18 p.cent). Only 2 patients had chest involvement. MRI was abnormal in 64 p.cent of cases showing pseudo-tumor, arachnoiditis, vascular lesions or medullar involvement. Outcome was good in all cases but two (one patient died and one patient had paraplegia possibly related to late diagnosis). Neurological manifestations of tuberculosis are extremely various in terms of clinical and radiological presentation. The best diagnostic test seems to be tuberculosis PCR. Outcome is frequently favorable if late diagnosis is avoided.

Prospective study of patients presenting with acute partial transverse myelopathy.

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.

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

Devic's 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 pathologies 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 presentation, laboratory findings (MRI and CSF) and clinical outcome. NMO patients were older and more frequently women than MS patients but the difference was not significant. CSF and MRI data were clearly different: oligoclonal bands (OCB) were found in 23% of NMO cases and 88% of MS (P < 0.001), abnormal brain MRI data were observed in 10% of NMO cases and 66% of MS (P < 0.001) and a large spinal cord lesion was observed in 67% of NMO cases and 7.4% of MS cases (P < 0.001). Clinical outcome was evaluated as more severe in the NMO group (P < 0.001). On 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. Our 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 pathologies but only when MRI data were applied. This finding could have implications for future therapeutic trials.

Double-blind crossover study with dolasetron mesilate, a 5-HT3 receptor antagonist in cerebellar syndrome secondary to multiple sclerosis.

Cerebellar syndrome is one of the most disabling developments in multiple sclerosis (MS). In neurodegenerative disorders, cerebellar syndrome is thought to be related to a neurochemical deficit of 5-hydroxytryptamine (5-HT). Previous studies found that a levorotatory form of 5-hydroxytryptophan, a 5-HT precursor, and ondansetron, a 5-HT(3) receptor antagonist, decreased cerebellar symptoms in Friedreich's ataxia and MS. We studied the effect of another 5-HT(3) receptor antagonist, dolasetron mesilate, on cerebellar syndrome in MS patients.Thirty-four MS patients were included in a placebo-controlled double-blind crossover study. They received a single dose of intravenous dolasetron mesilate or placebo. A quantitative evaluation of cerebellar syndrome using the nine-hole peg test and an ataxia score comprising static and kinetic parameters were performed before and after each treatment. No statistical difference was observed in the dolasetron mesilate group, compared with the placebo group. There was, however, inter-individual variability in the treatment response. This double-blind study on cerebellar syndrome in MS patients did not confirm the positive effect of dolasetron mesilate suggested by previous studies.