[Large granular lymphocyte leukemia: clinical and pathogenic aspects]. / Les leucémies à grands lymphocytes granuleux : de la clinique à la physiopathologie.

Large granular lymphocyte leukemia (LGL) is a hematologic disorder characterized by a monoclonal expansion of large lymphocytes containing azurophilic granules with a T CD3(+)CD57(+) or Natural Killer (NK) CD3(-)CD56(+) phenotype. The World Health Organization (WHO) classification identifies three entities: the T LGL, the chronic lymphoproliferative disorder of NK-cells, and the aggressive NK-cell leukemia. T LGL and chronic lymphoproliferative disorder of NK-cells are indolent diseases frequently associated with cytopenias and a wide spectrum of auto-immune manifestations. Neutropenia can lead to recurrent bacterial infections, which represent an indication of initiating a treatment in most of the cases. Immunosuppressive therapies are usually used in this context. In contrast, aggressive NK-cell leukemia follows a fulminant course with a poor prognosis because patients are refractory to most of the treatments. There is now a considerable interest in the pathophysiology of the disease with the perspective of new therapeutic options.

[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.

[Myasthenia gravis and pregnancy: clinical course and management of delivery and the postpartum phase]. / Myasthénie auto-immune et grossesse: évolution clinique, accouchement et post-partum.

OBJECTIVES: To study influences of pregnancy on the time-course of myasthenia gravis (MG) and of MG on pregnancy, delivery, postpartum and newborn. METHODS: We retrospectively collected data from 100 women affected with MG, hospitalized between 1994 and 2003 in departments of Neurology of Lille University Hospital. RESULTS: Eighteen patients had a total of 36 pregnancies, occurring 7.2 years on average after MG onset. MG exacerbation occurred in 7 patients (26 percent) during pregnancy and in 4 (14.8 percent) during postpartum. One patient died of acute respiratory failure during postpartum. Delay between the onset of MG and pregnancy was the only variable significantly associated with MG exacerbation: 5.8 years when exacerbation and 9.5 years when no exacerbation (p=0.03). Seven miscarriages, two therapeutic abortions and no death at birth were reported. Levels of anti-acetylcholine receptor antibodies were abnormal in 3 of 27 newborns (11 percent), but only one (3.7 percent) developed seronegative transient neonatal myasthenia gravis. DISCUSSION: During pregnancy, the clinical course of MG is variable but exacerbations were associated with a shorter delay between MG diagnosis and pregnancy. The risk of transient neonatal myasthenia gravis is relatively small but exists even when the parturient has stable MG without elevated levels of anti-acetylcholine receptor antibodies. CONCLUSION: Our study confirms pregnancy is more difficult to manage at the beginning of MG. Given the unpredictable course of MG during pregnancy, we recommend women affected with MG to begin a pregnancy when the disease is stable.

Unusual ocular motor findings in multiple sclerosis.

In multiple sclerosis (MS), nystagmus or internuclear ophthalmoplegia (INO) are the usual ocular motor dysfunctions. However, in patients with focal brainstem lesions, other rare manifestations may be observed, such as an isolated ocular motor nerve palsy or complex ocular motor disturbances. We report five MS patients with unusual ocular motor disturbances (bilateral third nerve palsy [n = 2], opsoclonus, Horner's syndrome and one-and-a-half syndrome). We discuss possible correlations between clinical disturbances and MRI abnormalities. Patients were seen in two MS centres. They had a confirmed diagnosis of MS and underwent a brain MRI and a complete neuro-ophthalmological work-up. In one case (opsoclonus), ocular motor manifestations were the first manifestation of MS. In the other four cases they occurred 3 months (Horner syndrome), 6 years and 12 years (bilateral third nerve palsy) and 2 years (one-and-a-half syndrome) after the disease onset, respectively. Four out of five patients were still in a relapsing-remitting form of MS. In the opsoclonus case, there was no evidence of a brainstem lesion. A gadolinium-enhanced lesion (2 cases) or a new T2-weighted lesion located in the brainstem correlated with the clinical presentation. All patients completely or partially recovered after corticosteroid infusions. Our study shows some rare or previously undescribed complex ocular motor symptoms in MS.

[Tonic pupils in Sjögren's syndrome]. / Syndrome de Gougerot-Sjögren et pupille tonique d'Adie.

INTRODUCTION: Adie's syndrome is usually a disease of unknown origin. We report two cases secondary to Sjögren syndrome. CASE REPORTS: A 26-year-old man developed in few months a sensitive neuropathy with a bilateral tonic pupil. A 50-year-old woman complained of sensitive signs probably related to a ganglionopathy and dysautonomic disorders affecting sudomotor and vasomotor functions. Adie syndrome had been diagnosed three years earlier. In both patients, the systemic signs and the results of the complementary tests led to the diagnosis of Sjögren's syndrome. Corticosteroids had limited effects on the sensitive signs and no influence on the tonic pupils. CONCLUSION: Adie syndrome, isolated or accompanied by other dysautonomic disorders, may reveal or precede the diagnosis of Sjögren's syndrome.

Autoimmune hepatitis and multiple sclerosis: a coincidental association?

In the present study we report, as part of a large multiple sclerosis (MS) cohort (1800 patients), three cases of untreated patients who developed autoimmune hepatitis (AIH). The prevalence of AIH in the general population is about 0.0169% and seems to be higher in our MS cohort (0.17%). We suggest that a liver biopsy should systematically be performed in untreated MS patients with a sustained increase of liver enzyme.

[Cortical blindness associated with Guillain-Barre syndrome: a complication of dysautonomia?]. / Cécité corticale associée à un syndrome de Guillain-Barré. Une complication de la dysautonomie?

INTRODUCTION: We report a case of a Guillain-Barre syndrome (GBS) with subarachnoid hemorrhage and regressive occipital white matter lesions. OBSERVATION: A 62-year-old woman developed ascendant progressive paresthesia and weakness of arms and legs, 48 hours after enteritis infection. Neurological examination showed tetraparesia with loss of deep tendon reflexes and alteration of proprioception tests. Nerve conduction studies revealed polyradiculoneuritis. Then she presented an acute blindness and hypertension. Brain magnetic resonance imaging showed bilateral occipital lesions and subarachnoid hemorrhage. Cerebrospinal fluid analysis revealed an elevated protein level (1.54 g/l) and red blood cells without meningitis. Brain arteriography was normal. Intravenous immunoglobulins improved neurological symptoms. CONCLUSION: Posterior localisation of reversible white matter lesions evoked a reversible posterior leukoencephalopathy. The implication of arterial hypertension caused by dysautonomia during GBS could be suspected.

[Neurological manifestations in Sjögren syndrome]. / Les manifestations neurologiques du Gougerot-Sjögren.

PURPOSE: To describe clinical and physiopathological aspects of neurological involvement in neurological Sjögren syndrome (SS) and to overview biological markers and therapeutical aspects. CURRENT KNOWLEDGE AND KEY POINTS: Neurological complications during SS may occur between 8.5 and 70%. Peripheral nervous system (PNS) involvement is well none but data concerning central nervous system (CNS) symptoms have been rarely described. In the present study we detail more precisely the heterogeneity of the neurological manifestation in SS. Recently new biological of SS such as alpha-fodrin antibodies have been described but there interest remain controversial. Furthermore, therapeutical data are scarce and there is to date no consensual guidelines for the therapeutical approach. PERSPECTIVE: Recent data concerning neurological involvement in SS confirm the heterogeneity of clinical presentations that may mimic stroke or multiple sclerosis. They underline the need for new biological markers. Furthermore, multicentric, randomized trials should be assessed in order to give us some therapeutical guidelines.

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.

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.

[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.

[Multiple sclerosis with sensory disturbances and hyperhidrosis of the hand]. / Troubles sensitifs associés à une hyperhidrose de la main révélatrice d'une sclérose en plaques.

INTRODUCTION: Hyperhidrosis may result from brain, spinal cord or peripheral nervous system injuries. We report the case of a 26-year-old patient who presented with sensorial disorders and focal hyperhidrosis of the right hand. OBSERVATION: MRI revealed multiple lesions very suggestive of active demyelinization. A lesion in the left paramedian posterior portion of the pons was enhanced after gadolinium infusion. The diagnosis of multiple sclerosis was suggested by MRI data and oligoclonal IgG bands on cerebrospinal fluid electrophoresis. CONCLUSIONS: Focal hyperhidrosis may be due to a lesion of the crossed sympathetic inhibitory tract. Although autonomic dysfunction is common during the late course of multiple sclerosis this case is, to our knowledge, the first report of focal hyperhidrosis revealing multiple sclerosis.

Ultrasound influence on the activation step before electroless coating.

This paper is devoted to the electroless plating of non-conductive substrates under ultrasound at 530 kHz. The ultrasonic irradiation is applied to the activation and to the plating steps. Effects are measured by following the final copper thickness obtained in 1 h of plating time, easily correlated to the average plating rate. It appears that ultrasound has a strong influence on the plating rates enhancement, and assumptions can be made that this increase could be linked to the catalyst cleaning. This is confirmed by XPS measurements.

[Bilateral phrenic nerve paralysis, dysautonomia and restrictive cardiomyopathy in a case of POEMS syndrome]. / Paralysie phrénique bilatérale, dysautonomie et cardiomyopathie restrictive dans un cas de syndrome POEMS.

We report a case of POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M protein and Skin changes) with unusual clinical features. A 62-year-old woman presented a severe polyneuropathy with dysphonia and vegetative symptoms, including bradycardia and sphincterial disorders. The clinical examination showed facial hyperpigmentation, cachexia, anasarca and splenomegaly. She also presented restrictive cardiomyopathy and endocrine disturbances. Nerve conduction studies revealed a severe demyelinating sensorimotor neuropathy. Cerebrospinal fluid analysis showed an elevated protein level. We detected a biclonal gammapathy (Ig G and Ig A with lambda light chain) and lytic pelvic bone lesions. Later, she developed a severe ventilatory failure due to a bilateral phrenic nerve paralysis leading to a mechanical ventilation. Steroids followed by localized radiotherapy partially improved the respiratory status and stabilized the neuropathy. Phrenic nerve paralysis, restrictive cardiomyopathy, vegetative symptoms and cranial nerve palsy are exceptional in POEMS syndrome. Moreover, this case emphasizes the importance of radiological investigations since the discover of plasmocytoma may improve the prognosis of POEMS syndrome.

[Late onset multiple sclerosis]. / Sclérose en plaques de début tardif.

Multiple sclerosis (MS) with clinical onset after 50 years old is unusual and frequently misdiagnosed. Clinical presentation and course seem also to be different that in MS occurring between 20 and 50 years old. The aim of this study was to evaluate the clinical and paraclinical characteristics of late onset MS. We respectively studied MS patients older than 50 years at the onset of the disease. We evaluated demographical data, clinical symptoms, cerebrospinal fluid (CSF), visual evoked potentials (VEPs) and MRI of these patients. We also studied clinical data during the follow-up with the occurrence of new symptoms and the evolution of the disease by the index of progression (EDSS unit per year). In a population of 1 417 MS, 3.4 p.cent had their first symptoms at 50 years old or older and 0.45 p.cent after 59 years old. At the time of the study patients had more frequently a progressive form: 37 p.cent had a primary progressive form and 35 p.cent a secondary progressive MS. None of the patients with onset after 60 years old had relapsing remittent MS. Motor symptoms were the most common neurologic presentation (54 p.cent of patients). Very few patients had a clinical optic nerve involvement during the follow-up. The mean progression index was 1 suggesting a most severe evolution in this subgroup of MS patients. 76 p.cent of patients had oligoclonal banding detected by CSF electrophoresis. The VEPs were abnormal in 81 p. cent of patients tested. 71 p.cent of the brain MRI were consistent with the diagnosis of MS. 60 p.cent of patients had spinal cord MRI abnormal. This study highlights the differences between the late onset MS and earlier onset. As previously reported, our study underlines the high frequency of progressive course, motor function involvement and poor prognosis.