Inaugural tumor-like multiple sclerosis: clinical presentation and medium-term outcome in 87 patients.

BACKGROUND: Tumefactive demyelinating lesions of the central nervous system can be the initial presentation in various pathological entities [multiple sclerosis (the most common), Balo's concentric sclerosis, Schilder's disease and acute disseminated encephalomyelitis] with overlapping clinical presentation. The aim of our study was to better characterize these patients. METHODS: Eighty-seven patients (62 women and 25 men) from different MS centers in France were studied retrospectively. Inclusion criteria were (1) a first clinical event (2) MRI showing one or more large demyelinating lesions (20 mm or more in diameter) with mass-like features. Patients with a previous demyelinating event (i.e. confirmed multiple sclerosis) were excluded. RESULTS: Mean age at onset was 26 years. The most common initial symptoms (67% of the patients) were hemiparesis or hemiplegia. Aphasia, headache and cognitive disturbances (i.e. atypical symptoms for demyelinating diseases) were observed in 15, 18 and 15% of patients, respectively. The mean largest diameter of the tumefactive lesions was 26.9 mm, with gadolinium enhancement in 66 patients (81%). Twenty-one patients (24%) had a single tumefactive lesion. During follow-up (median time 5.7 years) 4 patients died, 70 patients improved or remained stable and 12 worsened. 86% of patients received initial corticosteroid treatment, and 73% received disease-modifying therapy subsequently. EDSS at the end of the follow-up was 2.4 ± 2.6 (mean ± SD). CONCLUSION: This study provides further evidence that the clinical course of MS presenting with large focal tumor-like lesions does not differ from that of classical relapsing-remitting MS, once the noisy first relapsing occurred.

Central nervous system Aquaporin4 autoimmunity revealed by a single pseudotumoral encephalic lesion.

The radiological spectrum of neuromyelitis optica has become broader since the detection of aquaporin4 antibodies. We report a case of neuromyelitis optica patient with pseudotumoral encephalic lesion. A 66 year-old woman presented with sudden left lateral homonymous hemianopsia. A brain MRI showed an isolated and extensive right temporo-parieto-occipital lesion, involving periventricular white matter and the corpus callosum, with strong enhancement on post-gadolinium T1 weighted images, highly suggestive of lymphoma. Spinal cord MRI and body CT scan were unremarkable. Lumbar puncture showed pleocytosis, raised total protein level without abnormal cells or oligoclonal bands. A brain biopsy demonstrated non-specific demyelination. Serum aquaporin4 antibodies were positive, which was consistent with the diagnosis of neuromyelitis optica. Cases of central nervous system aquaporin4 autoimmunity presenting with an isolated brain lesion without optic neuritis or myelitis are extremely rare: this is the second case so far and the first one with advanced magnetic resonance characterization. Pseudotumoral encephalic lesions should include a large differential diagnosis, and testing aquaporin4 antibodies must be considered in order to avoid brain biopsy.

TIPIC Syndrome: Beyond the Myth of Carotidynia, a New Distinct Unclassified Entity.

BACKGROUND AND PURPOSE: The differential diagnosis of acute cervical pain includes nonvascular and vascular causes such as carotid dissection, carotid occlusion, or vasculitis. However, some patients present with unclassified vascular and perivascular changes on imaging previously reported as carotidynia. The aim of our study was to improve the description of this as yet unclassified clinico-radiologic entity. MATERIALS AND METHODS: From January 2009 through April 2016, 47 patients from 10 centers presenting with acute neck pain or tenderness and at least 1 cervical image showing unclassified carotid abnormalities were included. We conducted a systematic, retrospective study of their medical charts and diagnostic and follow-up imaging. Two neuroradiologists independently analyzed the blinded image datasets. RESULTS: The median patient age was 48 years. All patients presented with acute neck pain, and 8 presented with transient neurologic symptoms. Imaging showed an eccentric pericarotidian infiltration in all patients. An intimal soft plaque was noted in 16 patients, and a mild luminal narrowing was noted in 16 patients. Interreader reproducibility was excellent. All patients had complete pain resolution within a median of 13 days. At 3-month follow-up, imaging showed complete disappearance of vascular abnormalities in 8 patients, and a marked decrease in all others. CONCLUSIONS: Our study improved the description of an unclassified, clinico-radiologic entity, which could be described by the proposed acronym: TransIent Perivascular Inflammation of the Carotid artery (TIPIC) syndrome.

Optic neuritis revealing Kikuchi-Fujimoto disease.

Kikuchi-Fujimoto disease is a rare systemic disease with uncommon neurological involvement. We report the case of a 30-year-old Asian woman who presented a rapidly progressive loss of vision. Magnetic resonance imaging (MRI) of the optic nerve revealed an inflammation of the left optic nerve with chiasmatic involvement, without any encephalic or medullar lesion. Thoracic computed tomography scan showed bilateral axillary lymphadenopathy. Analysis of a biopsy of the axillary lymph node showed typical histological findings of Kikuchi-Fujimoto disease. There was no clinical or biological sign of associated systemic lupus erythematosus. The patient spontaneously recovered normal visual acuity in 4 weeks, with resolution of MRI abnormalities. No optic neuritis relapse or neurological event occurred in a 3-year follow-up. To our knowledge this is the first case of optic neuritis associated with Kikuchi-Fujimoto disease.

[Free floating thrombus on carotid megabulb or suspended bulb: what kind of dysplasia?]. / Thrombus flottant sur un mégabulbe carotidien ou sur un bulbe suspendu, quel type de dysplasie ?

Floating carotid thrombi are a rare cause of stroke mostly associated with atheromatous plaques, cardiogenic emboli, arterial dissections and systemic diseases related to coagulopathic states or iron deficiency anaemia. We report the cases of two patients with stroke and carotid megabulb or suspended bulb associated with floating thrombus. These findings are rarely described probably related to a form of arterial dysplasia and seem to be responsible of local haemodynamic modifications.

[Clinical polymorphism of myasthenia gravis beginning with isolated ocular symptoms; a five years retrospective analysis]. / Polymorphisme clinique de la myasthénie à point de départ oculaire; analyse rétrospective sur cinq ans.

INTRODUCTION: myasthenia gravis is a neuromuscular junction disorder that can jeopardize the patient's life and has a high clinical polymorphism that makes it difficult to diagnose. PATIENTS AND METHODS: after reviewing the disease physiology, its clinical symptoms, and the different means to diagnose and treat it, we present a 15-patient series that we cared for at the Rothschild ophthalmologic foundation from 2002 to 2007 for myasthenia gravis that began with isolated ocular symptoms, so as to highlight the clinical diversity of this pathology. RESULTS: when the disease was diagnosed, 11 patients out of 15 had a ptosis with diplopia, two had an isolated ptosis, and two had isolated diplopia. After investigations, we discovered that three patients had a malignant thymoma and one had thymic hyperplasia. An autoimmune disease association was found in two patients: the first one had Hashimoto thyroiditis and the second one developed optical neuromyelitis a few years after his myasthenia gravis. Only three patients secondarily developed a generalized myasthenia gravis. DISCUSSION: our series of patients has a low disease generalization rate in comparison with the published data in the medical literature, indicating that two-thirds of patients with ocular myasthenia gravis should develop generalized myasthenia gravis within approximately 2 years after the beginning of their illness. This could be explained by the early consultation of these patients and the common prescription of an immunosuppressive therapy, reducing the risk of secondarily generalized myasthenia gravis according to some studies. CONCLUSION: despite the small number of patients, this study underlines the clinical polymorphism of ocular myasthenia gravis and the risks it may cause. Close collaboration between ophthalmologists and neurologists is needed to ensure good care for these patients.

[Use of mitoxantrone in early multiple sclerosis with malignant disease course. Observational study in 30 patients with clinical and MRI outcomes after one year]. / Utilisation de la mitoxantrone dans les formes malignes inaugurales de sclérose en plaques. Etude observationnelle de 30cas. Evaluations cliniques et IRM à un an.

INTRODUCTION: In an observational multicenter study, we analyzed retrospectively 30 patients with malignant form of multiple sclerosis (MS) treated with mitoxantrone the year following the first neurological event. METHODS: The 30 patients were selected according to Weinshenker criteria of malignant MS (either a "catastrophic" relapse or a quickly aggressive form). We compared clinical and MRI findings the year before with the year following mitoxantrone onset treatment: annualized relapse rates (ARR), EDSS score and percentage of patients with gadolinium enhancing lesions on MRI. RESULTS: A total of 87 relapses were observed in the 5.7 months before and 10 during the year following onset of mitoxantrone treatment. The ARR decreased by 95% (6.0+/-2 before and 0.3+/-0.7 after). Twenty-four patients (80%) were relapse-free one year after onset of mitoxantrone treatment. The EDSS score improved in 87% of MS patients and the mean EDSS decreased by 1.9. Ninety-seven percent had at least gadolinium enhancing lesions before the start of mitoxantrone treatment as compared to 17% after. CONCLUSION: In our experience, mitoxantrone had a rapid and strong impact on the malignant forms of MS with a short disease duration. In this MS subgroup, mitoxantrone should be considered as an early treatment option.

[Neuro-ophthalmologic initial presentation of sarcoidosis]. / Manifestations neuro-ophtalmologiques révélatrices d'une neuro-sarcoïdose.

PURPOSE: To describe different forms of neuro-ophthalmologic onset of sarcoidosis: clinical signs, means of diagnosis, treatment, and progression. PATIENTS AND METHODS: Retrospective study of 13 patients with neuro-ophthalmologic initial onset of sarcoidosis diagnosed in three departments between 1997 and 2003. RESULTS: There were ten women and three men, with a mean age of 36 years. Six patients suffered from diplopia. In three cases, the cavernous sinus was involved; the three other patients with diplopia had meningoradiculitis. Nine patients had infiltration of the anterior visual pathway: the optic nerve was involved in five cases, the chiasm in two cases, and two patients had papilledema. Two patients also had both symptoms. The dosage of the angiotensin-converting enzyme level was evaluated in 11 patients and was elevated in six cases. Nine patients underwent a lumbar puncture; the cerebrospinal fluid protein was high in seven cases. Chest radiography and CT were abnormal in nine cases of 11. Ten patients had histological proof of sarcoidosis; the three others had enough evidence to support this diagnosis. All of them were treated with systemic corticosteroids. The diplopia improved for the six patients. Among the seven patients with optic nerve or chiasmal infiltration, one recovered completely, two were partially improved, and four remained stable. CONCLUSIONS: Diplopia and anterior visual pathway abnormalities can be the manifestation of initial onset of sarcoidosis; therefore this diagnosis must be kept in mind when these frequent neuro-ophthalmologic signs are encountered. Complementary exams, mainly biopsy of the involved areas with histological analysis, are needed to confirm this diagnosis. Corticosteroid treatment is generally followed by improvement, but relapses may occur.

Idiopathic acute transverse myelitis: application of the recent diagnostic criteria.

Despite an extensive diagnostic workup, some cases of acute transverse myelitis (ATM) remain of unknown etiology and have been referred to as "idiopathic" by the Transverse Myelitis Consortium group. In a retrospective study of 288 patients with ATM, 45 cases (15.6%) met the criteria for idiopathic ATM. The patients formed a relatively homogeneous group in terms of clinical and MRI data, but the prognosis was highly variable.

[Sub-cortico-frontal encephalopathy and choreic movements related to recombinant interferon-alpha 2b]. / Encéphalopathie sous-cortico-frontale et mouvements choréiques liés à l'interféron-alpha 2b recombinant.

Interferon (IFN)-alpha is associated with central nervous system (CNS) side effects such as depression and suicide ideation, somnolence, confusion, drowsiness, psychomotor slowing, memory impairment and visual disorientation. More severe complications are uncommon and include frank paranoia, dementia, coma, seizures and neuropathy. With the increasing long-term and extensive use of interferon (IFN)-alpha several new neurologic adverse effects have been recognized. We report on two patients who developed severe subcortico-frontal impairment, associated in one case with choreic movements, after a long-term treatment with IFN-alpha 2b for hematologic malignancies. Our patients rapidly and completely recovered from their cognitive and motor symptoms after the discontinuation of the drug. The same neurologic symptoms reappeared when we attempted to reintroduce lower doses of IFN-alpha in one case. Although little is known regarding IFN-alpha actions in the CNS, several possible mechanisms may underlie its neurotoxicity and might result from complex direct and indirect effects involving brain vasculature, neuroendocrine system, neurotoxic secondary cytokines'release and neurotransmitters.

Human T cell leukemia virus Type I (HTLV-I) infection induces greater expansions of CD8 T lymphocytes in persons with HTLV-I-associated myelopathy/tropical spastic paraparesis than in asymptomatic carriers.

A quantitative study of the T cell receptor repertoire was performed ex vivo on CD4 and CD8 T cell subsets of human T cell leukemia virus type I (HTLV-I)-infected asymptomatic carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Indexes of oligoclonality that compiled all repertoire modifications were calculated for peripheral blood mononuclear cells and for CD4 and CD8 T cell subsets. Both patients with HAM/TSP and asymptomatic carriers had greater T lymphocyte expansions than did uninfected donors, which was independent of age and at least twice higher in the CD8 than in the CD4 cell compartment. Some expanded CD8 T cells corresponded to cytotoxic T lymphocytes directed against various epitopes of the immunodominant Tax protein. Patients with HAM/TSP had significantly higher CD8 cell expansions than did asymptomatic carriers. These results highlight the prognostic value of measuring CD8 T cell expansions during follow-up of HTLV-I infection.

Sporadic inclusion body myositis in a patient with human T cell leukemia virus type 1-associated myelopathy.

Sporadic inclusion body myositis is a disease of unknown pathogenesis in which a viral etiology has long been suspected. We report a case that occurred in a patient with human T cell leukemia virus type 1-associated myelopathy. The diagnosis was confirmed by histopathological studies of the deltoid muscle. Nucleic acids amplification and in situ hybridization indicated the presence of integrated proviral DNA and viral mRNA transcripts in the lesions.

Common human T cell leukemia virus type 1 (HTLV-1) integration sites in cerebrospinal fluid and blood lymphocytes of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis indicate that HTLV-1 crosses the blood-brain barrier via clonal HTLV-1-infected cells.

In the spinal cord of patients with human T cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), infiltrating CD4(+) lymphocytes seem to be the major reservoir for the virus. Little, however, is known about the mechanisms by which HTLV-1 crosses the blood-brain barrier. An oligoclonal proliferation of HTLV-1-infected CD4 lymphoid T cells is present in the peripheral blood of all HTLV-1-infected individuals. Here, such oligoclonal distribution of HTLV-1-infected cells is evidenced in the cerebrospinal fluid (CSF) derived from 5 patients with HAM/TSP. Furthermore, clonal populations of HTLV-1-infected lymphocytes sharing the same HTLV-1 proviral flanking sequences (i.e. , integration sites in the cellular DNA), and thus derived from a single HTLV-1-infected progenitor, were found, for a given patient, in both the CSF and the peripheral blood. These data demonstrate that HTLV-1 crosses the blood-brain barrier by migration of HTLV-1-infected lymphocytes in vivo.

Evidence for the chronic in vivo production of human T cell leukemia virus type I Rof and Tof proteins from cytotoxic T lymphocytes directed against viral peptides.

Human T cell leukemia virus type I (HTLV-I) is a persistent virus that causes adult T cell leukemia and tropical spastic paraparesis/HTLV-I-associated myelopathy. Studies on rabbits have shown that viral proteins encoded by the open reading frames pX-I and pX-II are required for the establishment of the persistent infection. To examine the in vivo production of these proteins in humans, we have investigated whether cytotoxic T lymphocytes isolated from HTLV-I-infected individuals recognized pX-I and pX-II peptides. CD8(+) T lymphocytes to pX-I and pX-II peptides were detected in HTLV-I-infected individuals, whatever their clinical status, and even in the absence of any antigenic restimulation. These findings indicate that the HTLV-I pX-I and pX-II proteins are chronically synthesized in vivo, and are targets of the natural immune response to the virus.

Microangiopathy of the inner ear, retina, and brain (Susac syndrome): report of a case.

Microangiopathy of the inner ear, retina, and brain was first described in 1979 by John O. Susac. Since then, approximately 60 cases have been reported. Otolaryngologists must be aware of this syndrome, in which cochleovestibular symptoms are an important part of the diagnosis. In this article, we report a new case of Susac syndrome and discuss the diagnosis, physiopathologic characteristics, and treatment of this disease.

Persistent oligoclonal expansion of human T-cell leukemia virus type 1-infected circulating cells in patients with Tropical spastic paraparesis/HTLV-1 associated myelopathy.

The pattern of HTLV-1 replication was assessed through PCR amplification of the 3' proviral integration sites in patients with TSP/HAM at different times. Integration sites were sequenced and oligonucleotides specific for the flanking sequences were synthesized. Together with HTLV-1 LTR specific primers, clonotypic nested PCR was performed on peripheral blood from two patients. The frequencies of five clones studied ranged from 1/300 to 1/1500 PBMCs while four clones persisted for more than 1-5 years. It would seem that Tax driven expansion of T cells may persist for considerable periods of time in TSP/HAM despite strong cellular immunity. This may provide a background for the accumulation of subsequent mutations leading to malignancy.

Interaction of mouse hepatitis virus (MHV) spike glycoprotein with receptor glycoprotein MHVR is required for infection with an MHV strain that expresses the hemagglutinin-esterase glycoprotein.

In addition to the spike (S) glycoprotein that binds to carcinoembryonic antigen-related receptors on the host cell membrane, some strains of mouse coronavirus (mouse hepatitis virus [MHV]) express a hemagglutinin esterase (HE) glycoprotein with hemagglutinating and acetylesterase activity. Virions of strains that do not express HE, such as MHV-A59, can infect mouse fibroblasts in vitro, showing that the HE glycoprotein is not required for infection of these cells. The present work was done to study whether interaction of the HE glycoprotein with carbohydrate moieties could lead to virus entry and infection in the absence of interaction of the S glycoprotein with its receptor glycoprotein, MHVR. The DVIM strain of MHV expresses large amounts of HE glycoprotein, as shown by hemadsorption, acetylesterase activity, and immunoreactivity with antibodies directed against the HE glycoprotein of bovine coronavirus. A monoclonal anti-MHVR antibody, MAb-CC1, blocks binding of virus S glycoprotein to MHVR and blocks infection of MHV strains that do not express HE. MAb-CC1 also prevented MHV-DVIM infection of mouse DBT cells and primary mouse glial cell cultures. Although MDCK-I cells express O-acetylated sialic acid residues on their plasma membranes, these canine cells were resistant to infection with MHV-A59 and MHV-DVIM. Transfection of MDCK-I cells with MHVR cDNA made them susceptible to infection with MHV-A59 and MHV-DVIM. Thus, the HE glycoprotein of an MHV strain did not lead to infection of cultured murine neural cells or of nonmurine cells that express the carbohydrate ligand of the HE glycoprotein. Therefore, interaction of the spike glycoprotein of MHV with its carcinoembryonic antigen-related receptor glycoprotein is required for infectivity of MHV strains whether or not they express the HE glycoprotein.

Chronic myelopathy associated with human T-lymphotropic virus type I (HTLV-I).

PURPOSE: To review the clinical, epidemiologic, immunologic, and virologic aspects of the chronic myelopathy associated with human T-cell leukemia/lymphoma virus type I (HTLV-I), currently called tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). DATA IDENTIFICATION: Studies done after 1985, when TSP/HAM was first recognized, were identified by a computer search using MEDLARS II and CANCERLIT. Additional information was acquired from personal files and bibliographies of existing literature. STUDY SELECTION: A total of 400 articles, 90 book chapters, and 150 abstracts from meetings covering all aspects of HTLV-I and neurologic diseases were critically analyzed, and information from 250 publications was included. RESULTS OF DATA ANALYSIS: TSP/HAM is present in most HTLV-I endemic areas, with a prevalence ranging from 5.1 to 128 per 100,000 inhabitants. Up to 20% of patients develop TSP/HAM after transfusion of HTLV-I contaminated blood. Pathologic characteristics indicate a chronic meningomyelitis. The clinical features consist of a chronic progressive spastic paraparesis or paraplegia, sphincter disturbances, and minimal sensory loss. Supraspinal and peripheral nerve involvement is sometimes observed. High titers of HTLV-I-specific antibodies are present in the serum and cerebrospinal fluid. The high level of humoral and cellular immunologic response and the association of TSP/HAM with other immunologic diseases suggest an immune-mediated process. Corticosteroids and immunosuppressor treatment usually result in only short-term improvement. CONCLUSION: TSP/HAM is a common neurologic disease in many parts of the world. All patients with chronic progressive myelopathies should be tested for serum and cerebrospinal fluid HTLV-I-specific antibodies. Systematic screening of blood donors for HTLV-I is necessary to help prevent the dissemination of the virus and the occurrence of post-transfusional cases.

High level of HTLV-I specific protein expression in a patient with adult T-cell leukemia, chronic progressive myelopathy and Kaposi's sarcoma.

Analysis was made of serum anti-HTLV-I antibodies, virus-specific proteins in peripheral blood lymphocytes (PBL) and proviruses in lymphocyte DNA of a patient with adult T-cell leukemia (ATL), Kaposi's sarcoma, and chronic myelopathy. Using Western blot and PCR (with HIV-1 specific primers), it was shown that Kaposi's sarcoma was not linked to HIV infection. Western blot analysis of serum revealed antibodies against p19, p24 and Pr 53 of HTLV-I. Examination of proteins in fresh PBL by Western blot revealed a high level of HTLV-I specific protein expression. Southern blot analysis of the patient's DNA revealed two different sites for HTLV-I provirus integration.