Demyelinating disease in SLE: Is it multiple sclerosis or lupus?

Among the 12 systemic lupus erythematosus (SLE)-related central nervous system (CNS) syndromes defined by the American College of Rheumatology (ACR), demyelinating syndrome and myelopathy are two of the less prevalent and more poorly understood ones. One important issue concerning demyelinating disease in SLE is that it can be easily misdiagnosed with other central nervous system demyelinating disorders such as multiple sclerosis (MS). A clinically isolated neurological syndrome can be the presenting feature before other concomitant symptoms of SLE appear or definite MS is diagnosed. Although challenging, some diagnostic tests used in clinical practice and research may help to differentiate between these entities. These tests have improved the understanding of the pathogenesis in these diseases, but some points, such as the role of antiphospholipid antibodies in SLE-associated transverse myelitis, remain unclear and are a matter of ongoing debate.This review discusses clinical, pathophysiological, radiological and therapeutic concepts of demyelinating disease of the CNS in SLE, focussing on its differentiation from MS and its relation with other CNS demyelinating processes, such as transverse myelitis, optic neuritis and neuromyelitis optica.     

Myelitis associated with atopic disorders in Japan: a retrospective clinical study of the past 20 years

OBJECTIVE: To clarify the clinical features of myelitis associated with atopic disorders in Japanese patients. SUBJECTS AND METHODS: We retrospectively studied the clinical, immunological and electrophysiological features of 68 consecutive patients with myelitis of acute or subacute onset diagnosed at Kyushu University Hospital during the past 20 years. RESULTS: While only 2 of 28 (7%) patients with myelitis diagnosed between 1979 and 1993 had either atopic dermatitis (AD) or bronchial asthma (BA), 19 of 40 (48%) patients with myelitis diagnosed between 1994 and 1998 did. Among the 40 patients with myelitis diagnosed between 1994 and 1998, 19 patients with either AD or BA as well as 21 patients without either disease showed a significantly higher level of serum total IgE, higher frequency of hyperIgEaemia and higher frequency of mite antigen-specific IgE than 82 healthy controls. Myelitis patients with AD presenting as persistent paresthesia/dysesthesia in all four limbs showed cervical cord lesions on MRI and abnormalities in upper limb motor evoked potentials but no abnormalities in the cerebrospinal fluid (CSF), while myelitis patients with BA showed preferential involvement of the lower motor neurons clinically and electromyographically. In addition, 12 patients with myelitis who had hyperIgEaemia and mite antigen-specific IgE but neither AD nor BA showed incomplete transverse myelitis with mild motor disability and few CSF abnormalities. CONCLUSION: The clinical features of myelitis associated with atopic disorders were in part distinguished by the type of preceding atopic disorder, and also were different from those of hyperIgEaemic myelitis with no preceding atopic disorders.     

Myelopathy revealing lupus. Two cases and review of the literature

INTRODUCTION: Myelopathy is a rare manifestation of systemic lupus erythematosus, occurring most often during the course of the disease. EXEGESIS: We report two cases of women with myelopathy as the first manifestation of systemic lupus erythematosus; both had an unusual course. We review the literature for previously reported cases. CONCLUSION: The clinical presentation of myelitis is heterogeneous. Usually, neurologic deficits evolve within a few hours (typically acute transverse myelitis) and outcome is usually poor. However, chronic or recurrent transverse myelitis has also been reported, including relapsing myelitis that resolved spontaneously. Myelopathy can be the first manifestation of the disease and this might be more common than initially thought. Magnetic resonance imaging (MRI) findings depend on the timing of the examination and the stage of the disease; the MRI may therefore be normal. An association with optic neuritis is frequently reported in the literature and differential diagnosis with multiple sclerosis may be difficult. Overlapping features between both diseases have been termed "lupoid sclerosis" and are actually classified as demyelinating syndromes associated with lupus. Myelopathy does not appear to be consistently associated with antiphospholipid antibodies, as has been previously suggested. The best treatment protocol has not been determined; however, in recent years, pulses of methylprednisolone and cyclophosphamide have gained acceptance by most authors.     

Primary Sjögren's syndrome or multiple sclerosis? Our experience concerning the dilemma of clinically isolated syndrome

The authors present the case of a 50 years old woman who during 3 years had a transient right limbs palsy, and numerous episodes of unilateral/bilateral optic neuropathy. The CSF and MRI examinations did not sustain the diagnosis of multiple sclerosis (MS). After 2 years from the onset, she presented bilateral trigeminal neuropathy, and after 9 months the anti-SS-A and anti SS-B antibodies were positive. The sialography and the minor salivary ducts biopsy (in the absence of xerostomia and xerophthalmia) have established the diagnosis of primary Sj?gren's syndrome (pSS). Subsequently, the patient presented spastic paraparesis, the clinical and imagistical features have suggested the diagnosis of acute transverse myelitis C4-T4. The treatment administered (corticosteroids and IGIV) improved the clinical state. The authors analyse then cases with SLE and cases with pSS, whose initial diagnosis was MS possibly with no evidence of collagen tissue disorders (CD) for many years. In conclusion, screening for biomarkers of SLE or pSS should be systematically performed in a case of acute or chronic myelopathy. Some laboratory tests as CSF examination, the antibodies type, cranial and spinal MRI, are useful for the differential diagnosis with MS. In a neurological clinically isolated syndrome (CIS) the diagnosis of MS should be precautiously established; the close follow-up of patients is always necessary, those with atypical neurological symptoms for MS, relapsing-remitting form, or lack of response to the common treatment for MS, should be examined for CD.     

Cytomegalovirus-associated transverse myelitis in a non-immunocompromised patient

Cytomegalovirus (CMV)-associated transverse myelitis is rare in immunocompetent patients. The case of a 54-year-old man is reported here who developed acute transverse myelitis with cerebrospinal fluid (CSF) alterations, suggesting a central nervous system infection. CMV-IgM positivity in serum and CMV isolated from blood, positive CMV PCR and positivity for pp65 antigen in blood, without viral antigens in the CSF and a positive response to therapy with ganciclovir (followed by progressive improvement) supported the diagnosis.     

Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement

Symptoms originating from central nervous system (CNS) are frequently occuring in patients with systemic lupus erythematosus (SLE). Reliable diagnostic markers for this condition are presently lacking. Importantly, CNS involvement in lupus patients is associated with increased morbidity and mortality. The aim of this retrospective evaluate was to study the diagnostic value of cerebrospinal fluid (CSF) cytokine levels in SLE patients with CNS involvement. 34 patients with SLE were hospitalized and investigated for the presence of CNS lupus. These patients were evaluated clinically and with magnetic resonance imaging (MRI) and CSF analyses, as well as with neuropsychiatric tests. 13 patients were found to have CNS lupus whereas another four of the patients fulfilled the criteria for CNS involvement but were excluded from this group due to other causes of CNS involvement. Lastly, in 17 SLE cases, the diagnosis of CNS lupus could not be confirmed. CSF levels of interleukin-6 (IL-6) and IL-8, as well as the CSF/serum IL-6 ratio, were elevated in the CNS lupus group, compared with the 17 SLE patients not fullfilling a diagnosis of cerebral lupus. Interestingly, follow-up of five patients being successfully treated for CNS lupus revealed profound decrease of intrathecal IL-6 levels. These results indicate that analysis of CSF cytokine levels, especially IL-6 and IL-8, may be useful in the diagnostics and possibly follow-up of SLE patients with cerebral lupus.     

Transverse myelitis,a rare neurological manifestation of mixed connective tissue disease—a case report and a review of literature

Although neurological involvement occurs in about 10% of patients with mixed connective tissue disease (MCTD), acute transverse myelitis (TM) has only been described in seven cases of MCTD. We hereby report a case of 70-year-old white female with transverse myelitis complicating her underlying MCTD. Our patient presented with lower extremity weakness, loss of sensation and incontinence one year after her diagnosis of MCTD. Her work-up revealed an abnormal MRI, with findings consistent with TM. She had an excellent response to initial therapy with six cycles of monthly intravenous immunoglobulins and steroids, with subsequent maintenance on azathioprine. She had a good neurological recovery with mild residual sequelae only. On basis of this case report and review of literature, we recommend ongoing surveillance and reporting of this rare neurological presentation in MCTD.     

Transverse myelitis: a manifestation of systemic lupus erythematosus strongly associated with antiphospholipid antibodies

All 4 patients with transverse myelitis (TM) included in a prospective study of 500 patients with systemic lupus erythematosus (SLE) tested for anticardiolipin (aCL) antibodies were found to be positive. To determine if the apparently strong association between transverse myelitis and antiphospholipid antibodies (aPLA) in patients with SLE continued to hold, we chose 12 patients with SLE with transverse myelitis from 2 institutions. Eleven of the 12 patients with SLE were tested for aCL and all but one was positive. Most of them (n = 8) had both IgG and IgM isotype aCL. The one who was negative had had a positive VDRL and prolonged APTT 15 months earlier, coinciding with the episode of transverse myelitis. One patient died before she was tested for aCL but she also had a false positive VDRL. Thus, all 12 patients with SLE with transverse myelitis had evidence of aPLA. We conclude that there is strong association between transverse myelitis in SLE and the presence of aPLA.     

Neuromyelitis Optica-AQP4: An Update

Devic disease (neuromyelitis optica [NMO]) is an idiopathic inflammatory demyelinating and necrotizing disease characterized by optic neuritis and transverse myelitis, either simultaneously or in isolation. NMO is often idiopathic but may also be associated with systemic autoimmune disease. The prognosis of NMO is severe, especially in those with early and recurrent relapses. MRI studies have revealed that most frequently, there is a long spinal cord lesion that extends through three or more vertebral segments in length. NMO-IgG is the first antibody marker for any inflammatory central nervous system disorder and is both sensitive and specific for NMO. The identification of NMO-IgG in patients with recurrent optic neuritis or longitudinally extensive myelitis and its ability to predict subsequent relapse support the concept of a spectrum of NMO disorders. Treatment in the acute phase includes intravenous steroids and plasma exchange therapy. Immunosuppressive agents are recommended for the prophylaxis of relapses.     

Central nervous system infections in patients with systemic lupus erythematosus

OBJECTIVE: To evaluate the clinical profiles of patients with systemic lupus erythematosus (SLE) with central nervous system (CNS) infections. METHOD: We retrospectively reviewed patients with SLE with CNS infections from January 1983 to June 2003. The clinical features, laboratory data, and prognoses of these patients were recorded. RESULTS: During the 20-year review period, 17 SLE patients with CNS infections were identified. The mean age at CNS infection was 29.6 +/- 15.3 years. Cryptococcal infection was identified in 10 patients and bacterial meningitis in 7. Most patients (94%) had active SLE at the time of CNS infection. Fifteen patients received corticosteroid therapy and of these, 7 received it in conjunction with immunosuppressive agents. The most common presentation was headache, fever, and vomiting. The mortality rate among the 17 patients was high (41.2%). CONCLUSION: Cryptococcal meningitis played the major role in CNS infection of patients with SLE, and it cannot be ruled out even when the cerebrospinal fluid (CSF) white blood cell count is within normal range. CSF India ink and latex agglutination testing for cryptococcal antigen should be performed and are effective screening tools to establish an early diagnosis.     

Diagnostic reliability of cerebral spinal fluid tests for acute confusional state (delirium) in patients with systemic lupus erythematosus: interleukin 6 (IL-6), IL-8, interferon-alpha, IgG index, and Q-albumin

OBJECTIVE: Acute confusional state (ACS) is an uncommon but severe central nervous system (CNS) syndrome in systemic lupus erythematosus (SLE) defined by clinical manifestations. To develop useful and reliable diagnostic tools for ACS, we evaluated the association of cerebral spinal fluid (CSF) tests with ACS and their predictive values for the diagnosis of ACS in SLE. METHODS: We performed a prospective study using a cohort of 59 patients with SLE and compared those with and without ACS. Associations between ACS and each CSF test [interleukin 6 (IL-6), IL-8, interferon-alpha, IgG index, and Q-albumin] were statistically evaluated. Each patient underwent all CSF evaluations. RESULTS: ACS was diagnosed in 10 patients (ACS group), SLE-related CNS syndromes except ACS in 13, and no CNS syndromes in 36 (non-CNS group). CSF IL-6 levels in the ACS group were significantly higher than those in the non-CNS group (p < 0.05). A positive IgG index (p = 0.028) was significantly associated with ACS. No other test showed a significant association with ACS. The positive and negative predictive values for the diagnosis of ACS in SLE were 80% and 85% for elevated CSF IL-6 levels (> or = 31.8 pg/ml), and 75% and 83% for the IgG index, respectively. CONCLUSION: No single CSF test had sufficient predictive value to diagnose ACS in SLE, although CSF IL-6 levels and the IgG index showed statistical associations with ACS. Use of CSF tests combined with careful history and clinical examinations is recommended for proper diagnosis of ACS in SLE.     

Epstein-Barr virus infections of the central nervous system

OBJECTIVE: Epstein-Barr virus (EBV), a lymphotropic herpes virus causing infectious mononucleosis (IM), also causes various central nervous system (CNS) infections. In the present study, EBV CNS infections were investigated. PATIENTS AND METHODS: For adult inpatients in our hospital and related hospitals between 1984-2002, CNS syndromes with IM symptoms were examined, and serologic positives were assessed according to established criteria. Polymerase chain reaction (PCR) was performed for cerebrospinal fluid (CSF) from seven patients. RESULTS: Ten patients with EBV-related CNS infections were found; their mean age was 36 years (20-79 years). The neurologic forms were as follows: acute encephalitis (4 patients), acute cerebellar ataxia (1), acute disseminated encephalomyelitis (ADEM) (2), myelitis (1), and meningitis (2). The PCR from CSF was positive in two patients with meningitis, one patient with ADEM, and one patient with encephalitis-associated chronic EVB infection. One case of encephalitis and another of relapsing ADEM were attributed to chronic EBV infection. CONCLUSION: Our study identified a variety of EBV-related CNS infections. EBV CNS infections are divided into two groups: 1) CNS syndromes associated with primary EBV or reactivated infection, and 2) those associated with chronic EBV infection; it is notable that in the former, diverse CNS syndromes including ADEM can occur, whereas in the latter, chronic or recurrent CNS syndromes are produced.     

Transverse myelitis in systemic lupus erythematosus--the effect of IV pulse methylprednisolone and cyclophosphamide.

Transverse myelitis is a rare but serious complication of systemic lupus erythematosus (SLE). Standard treatment with medium to high doses of oral prednisone has been inadequate to control neurologic sequelae, and patients remain confined to a wheel chair or even die. We employed aggressive treatment in 7 patients with transverse myelitis complicating SLE with pulse methylprednisolone for acute episodes followed by pulse cyclophosphamide for a mean of 6 months; most of our patients are currently able to walk and have partial or total sphincter control.     

Systemic lupus erythematosus associated with benign intracranial hypertension: a case report]

A case of systemic lupus erythematosus (SLE) with benign intracranial hypertension (BIH) is reported. A 41-year-old male with a history of SLE starting in 1982 was admitted to our hospital in December 1989 because of headache and vertigo. Laboratory examinations on admission showed proteinuria, mild anemia, and positive antinuclear and anti-Sm antibodies. No abnormal findings except high pressure of 350 mmH2O were observed in his cerebrospinal fluid (CSF). Fundoscopic examinations showed marked bilateral papilledema and retinal bleeding. Brain CT, MRI and angiography revealed diffuse brain edema without space occupying lesion and cerebrovascular diseases. Because there were no diseases such as endocrinological disorders, severe anemia, and no history of the administration of drugs which might cause intracranial hypertension, the diagnosis of BIH was made. Subsequently, he was treated with intravenous methylprednisolone therapy and osmotic diuretics and his clinical symptoms and pressure of CSF gradually improved. The decrease of CSF adsorption was observed with RI cisternography in our case. Psychosis, seizures and meningitis are common CNS manifestations in SLE patients. But BIH is very rare and its cause is unclear. Only 17 cases of SLE with BIH have been reported. The pathogenesis and treatment of BIH in SLE patients were discussed in this paper.     

Cerebrospinal fluid and serum prolactin in systemic lupus erythematosus with and without central nervous system involvement

Aim: Recent research has shown that prolactin (PRL) may participate in the pathogenesis of systemic lupus erythematosus (SLE) and hyperprolactinemia may be related to disease activity. The current study investigated both serum and cerebrospinal fluid (CSF) PRL in SLE patients and their possible relationship to central nervous system (CNS) involvement. Methods: Prolactin levels were determined by immunoradiometric assay. Serum PRL levels were detected in 80 patients with SLE and 25 matched healthy controls. Disease activity was scored by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). CSF PRL levels were detected in seven cases of CNS involving SLE, eight cases of non‐CNS involved inactive SLE and eight cases of non‐SLE CNS disorders. Results: Hyperprolactinemia was present in 40% of SLE patients. Serum PRL levels were significantly correlated with SLEDAI scores. There was no significant difference in serum PRL levels between SLE patients with or without CNS involvement, but the mean CSF PRL levels were higher in CNS‐involved SLE patients than in non‐CNS‐involved SLE and non‐SLE patients. There was no significant correlation between serum and CSF PRL levels. Conclusions: Our results suggest that high serum PRL levels correlate with active disease in SLE, but not with CNS involvement. CSF PRL levels in SLE patients correlate with CNS involvement, which indicates that CSF PRL may be involved in the pathogenesis of CNS‐SLE.     

Pattern of neuropsychiatric manifestations and outcome in juvenile systemic lupus erythematosus

The aim of this study was to study the neuropsychiatric (NP) manifestations, diagnostic evaluation, treatment and outcome in juvenile systemic lupus erythematosus (SLE). We reviewed the charts of all children with SLE and evidence of NP manifestations as defined by the presence of at least one of the following: headache, cerebrovascular accident (CVA), chorea, seizure, papilledema, and psychiatric or spinal cord manifestations. Out of 90 children with SLE, 20 (16 female) had NP manifestations. The mean age at onset was 8.8 years. The mean period between onset of SLE and NP manifestations was 10.2 months. NP manifestations were the presenting feature in 3 patients. Eleven patients had headache, 10 had psychiatric manifestations, 10 had seizure and 6 had CVA. Coma was seen in 5 patients, chorea in 4, transverse myelitis in 2 and papilledema in 2. Anticardolipin antibodies were high in 12 patients. Five patients had an abnormal CSF study. Nine patients had EEG abnormalities and 13 showed MRI abnormalities. All patients received oral prednisone and 17 were treated with IVMP and immunosuppressive therapy (cyclophosphamide or azathioprine); 85% of our patients recovered completely, but 15% had persistent NP sequelae; 10% died from severe infection. In conclusion, NP involvement in juvenile SLE is common. However, early diagnosis and early treatment with adjunctive intravenous pulse cyclophosphamide may improve the outcome.Abbreviations CVA Cerebrovascular accident - IVMP Intravenous methylprednisolone - NP Neuropsychiatric - SLE Systemic lupus erythematosus     

St Louis encephalitis in Ohio, September 1975: clinical and EEG studies in 16 cases.

In 1975, during the largest epidemic of St Louis encephalitis (SLE) in the United States, 416 cases were diagnosed in Ohio. Persons who were admitted to two Columbus (Ohio) hospitals with suspected acute viral CNS infection were prospectively studied to define the virologic and clinical aspects of SLE. Sixteen cases of SLE were diagnosed serologically. Fifteen patients had signs of encephalitis and one had aseptic meningitis. Six patients had the syndrome of inappropriate antidiuretic hormone secretion. Other frequent findings included moderate peripheral leukocytosis and CSF pleocytosis, with mild elevation of CSF protein levels but normal glucose levels. Severe neurologic sequelae were infrequent. The EEG proved valuable in diagnosis and prognosis. Results of brain scans were normal. Virus in CSF or urine was not demonstrated, nor was viral antigen in CSF or urine sediments. Specific antibody was found in the sera and CSF of all patients who were tested, but interferon was not detected.     

Cerebrospinal fluid immunoglobulins and neuronal antibodies in neuropsychiatric systemic lupus erythematosus and related conditions

Neuronal antibodies found in the cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus (SLE) may be locally produced, or may enter through a damaged blood-brain barrier. We measured CSF serum/albumin and IgG ratios, oligoclonal banding, and paired CSF/serum neuronal antibody in 36 patients and 98 controls. Only 14% of SLE CSF contained neuronal antibodies; 80% of these had clinically overt neuropsychiatric manifestations. None of 73 patients with noninflammatory central nervous system (CNS) disease had CSF-neuronal antibodies, compared with 8/61 with SLE or related inflammatory CNS disorders (p less than .001). In SLE, CSF neuronal antibodies were accompanied by high titer serum neuronal antibodies (p less than 0.03) or abnormal Q-albumin and occurred only when serum neuronal antibodies were present. CSF-neuronal antibodies appear to be related to immune-inflammatory CNS disease, especially SLE, and may traverse a damaged blood-brain barrier.     

Longitudinal myelitis in systemic lupus erythematosus

Introduction

Myelitis occurs in less than 5% of the patients during the disease course of systemic lupus erythematosus (SLE). Longitudinal myelitis, characterized by inflammatory involvement of at least four medullar segments, is a particular form of myelitis.

Case report

We report a 31-year-old woman with SLE, admitted for paraparesia and delirium. Lumbar puncture and MRI led to the diagnosis of longitudinal myelitis. The patient rapidly improved after corticosteroid therapy.

Conclusion

Transverse myelitis in SLE patients has been already commonly reported, but longitudinal myelitis is uncommon. Longitudinal myelitis has to be suspected in case of paraplegia or tetraplegia, with sensory defects and bladder dysfunction. MRI shows typically T2 medullar hypersignals. This may result in neurologic sequela. Cyclophosphamide has been used in patients where corticosteroids were inefficient.