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Epilepsy and Behcet's disease: Cortical and hippocampal involvement in Brazilian patients
Abstract
To describe clinical, radiological and electrophysiological findings in epileptic neuro-Behçet's (NBD) patients.
A retrospective review of 178 medical records of Behçet's disease patients was conducted in Brazil. Information on gender, ethnicity/skin color, age at symptom onset and age at onset of neurologic manifestations, type of seizures, clinical manifestation of the disease, use of antiepileptic drugs and immunosupressors was collected from medical records of all epileptic NBD patients. Brain MRI, cerebrospinal fluid (CSF) analysis and electroencephalograms (EEG) were assessed.
Forty NBD cases were identified, of which seven patients (17%) presented epilepsy. In five patients seizures occurred during an acute exacerbation of the disease, and in one patient they occurred six months after meningoencephalitis. One patient presented seizures in the progressive form of the disease and five patients had complex partial seizures. The EEG showed temporal involvement in three patients and frontal in one. Hippocampal lesions were identified in three patients and cortical lesions in five. All patients had good response to antiepileptic drugs and are seizure-free, except for one who developed refractory seizures.
Brazilian NBD patients showed a high prevalence of epilepsy, mainly complex partial seizures, occurring at any phase of the disease. Epileptic NBD patients may have cortical and hippocampal lesions that could explain the occurrence of epilepsy.
... Raised CSF IL-6 levels are usually associated with raised CSF cell count and protein, and these three parameters have been associated with disease activity and outcome over 3 years [22]. The reversibility of lesions in parenchymal NBD supports the venous inflammatory pathophysiology and many patients evolve with brainstematrophy after inflammation is resolved [23]. Some of them may present a pseudotumoral form of the disease, usually involving the capsule-thalamic region or cortex, with more severe clinical presentation at diagnosis but with good recovery [24] (Figure 2). ...
... Epilepsy frequency varies from 4-27%, according to the population [16,17,20]. Seizure can be generalized or focal, and occur during an acute neurologic manifestation of the disease, quiescent phase or progressive form of NBD [23,[27][28][29]. Although previous studies showed that seizures are more commonly secondary to medications and other provoking factors, some patients with NBD and epilepsy may present frontal or hippocampal involvement that justify the occurrence of seizures [23]. ...
... Seizure can be generalized or focal, and occur during an acute neurologic manifestation of the disease, quiescent phase or progressive form of NBD [23,[27][28][29]. Although previous studies showed that seizures are more commonly secondary to medications and other provoking factors, some patients with NBD and epilepsy may present frontal or hippocampal involvement that justify the occurrence of seizures [23]. The occurrence of seizures is associated with a high mortality rate [29]. ...
Behçet's disease (BD) is an inflammatory disorder characterized by recurrent oral and genital ulcers, ocular inflammation, arthritis and skin lesions. Neuro-Behçet's disease (NBD) is found in 5–30% of patients and is classified into parenchymal and non-parenchymal manifestations. Most common parenchymal NBD manifestation is brainstem meningoencephalitis and patients may also have cranial nerve palsies, myelitis, epilepsy and peripheral neuropathy. Non-parenchymal NBD manifestations are cerebral venous thrombosis and aseptic meningitis. NBD usually develop abruptly and generally clear completely within weeks, however a third of patients evolve with progressive course. Moreover, patients with BD without overt neurological manifestations may present silent neurological involvement, with abnormal findings on neuropsychological, neurophysiological and neuroimaging studies. NBD is an adverse prognostic factor. Herein we review NBD manifestations and its treatment.
... 8,2021 reported cases with hippocampal lesions in NBD (Table 1). 10,11) However, these patients who manifested focal seizures had good responses to antiepileptics, and one of the authors speculated that the seizures were possibly related to chronic inflammatory reaction to the small vessels that supply the mesial temporal lobe. 10) The lesions in the hippocampus reported in two of the four cases disappeared after steroid therapy, and no report of a resolved NBD lesion becoming epileptogenic was found. ...
... 10,11) However, these patients who manifested focal seizures had good responses to antiepileptics, and one of the authors speculated that the seizures were possibly related to chronic inflammatory reaction to the small vessels that supply the mesial temporal lobe. 10) The lesions in the hippocampus reported in two of the four cases disappeared after steroid therapy, and no report of a resolved NBD lesion becoming epileptogenic was found. Second, elevation of IL-6 levels >16.0 pg/mL has been proposed to be one of the diagnostic criteria of CP-NBD. ...
Behçet’s disease (BD) is a rare chronic inflammatory disease associated with systemic vasculitis. Involvement of the nervous system in BD is called neuro-BD (NBD). Epilepsy related to NBD is uncommon but responds well to anti-epileptic drugs. We present a case of NBD with drug-resistant mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS). The patient presented with headache, dizziness, disorientation, and generalized seizures. Magnetic resonance imaging (MRI) identified pontine lesions. Chronic inflammation was suspected, and steroid pulse therapy improved his symptoms. He relapsed 1 year after onset and was diagnosed with NBD. MRI revealed bilateral mesial temporal lesions, with the right being edematous and the left atrophic. NBD was controlled by steroid and immunosuppressive medication. Three years after the onset of NBD, the patient suffered MTLE, and MRI suggested left hippocampal atrophy. His seizures became drug-resistant and surgical therapy was considered 12 years after NBD onset. Pre-surgical MRI clearly showed left HS. After evaluations, the patient had left anterior temporal lobectomy (ATL) 13 years after NBD onset under stable NBD. The patient was seizure-free for > 2 years after surgery. Surgery will be an effective treatment for drug-resistant MTLE with HS even in patients with NBD, of course the effects of surgical intervention should be considered.
... Cortical or hippocampal lesions were identified in six epileptic NBD patients (Fig. 1). We suspect that those lesions were related to the occurrence of seizures as we previously described [14]. ...
... Furthermore, no independent variables were related to the development of NBD relapses, despite the 18 relapsing patients in this study. Because time to diagnosis and treatment options may influence the number of relapses, we hypothesized that the low threshold for diagnosis BD in Brazil [14,15] and consequently later institution of immunosuppressive treatment may have contributed to the higher number of relapses verified in this series. ...
Type and frequency of systemic and neurologic manifestations of Behçet's disease (BD) vary with ethnicity. In Brazil, BD occurs as sporadic cases. We describe clinical and radiological features of 36 Brazilian patients of mixed ethnicity with neuro-Behçet's disease (NBD). Medical records of 178 BD patients were reviewed and 36 (20%) NBD patients were identified. Twenty-one NBD patients (58.3%) were female and 27 (75%) presented with parenchymal manifestations. Brainstem involvement was the most common neurologic syndrome (41.7%). Seizures (27.8%), isolated aseptic meningitis (16.7%), optic neuropathy (ON) (16.7%), cerebral venous thrombosis (CVT) (8.3%), peripheral neuropathy (2.8%), and spinal cord involvement (5.6%) were other neurologic manifestations observed among Brazilian NBD patients. Eighteen (50%) had at least one relapse, and isolated aseptic meningitis was the most common relapsing manifestation. No significant differences concerning the number of relapses between parenchymal and non-parenchymal groups were found. A multivariate model including disease duration, cell count in spinal fluid, cyclosporine use, immunosuppressive use at disease onset, age at NBD onset, and ON did not reveal any significant associations with NBD relapse. There was a low frequency of CVT and an unexpected higher number of isolated aseptic meningitis. Brazilian NBD patients present more parenchymal and atypical manifestations, and relapse more often than NBD patients from other populations.
... 141 Partial-onset seizures and epilepsia partialis continua have been reported. [142][143][144] cognitive disorders ...
Neurological involvement in Behçet’s syndrome arises predominately through an inflammatory meningoencephalitis characterised by perivenular inflammation due to activation of Th-17 immunological pathways. The brainstem is involved in 50% of cases, the diencephalon and other areas of the brain in 30%, and the spinal cord in 10%. Movement disorders and epilepsy may occur. Psychiatric syndromes may arise with brain and brainstem involvement, and cognitive disorders relate to the brain disease, to circulating inflammatory factors, and to fatigue and despondency. Eighty per cent of cases begin with a relapsing disease course, of whom 70% have only one attack, and 30% have a progressive disease course either from onset or following an initially relapsing course. Venous thrombosis leading to intracranial hypertension and cerebral venous infarction is less common and caused by inflammation in affected veins and a circulating prothrombotic state. Arterial involvement is rare and relates to an arteritis affecting large-sized and medium-sized vessels within the brain leading to infarction, subarachnoid and parenchymal haemorrhage, aneurysm formation and arterial dissection. There is a newly recognised disorder of cerebral cortical hypoperfusion. Cranial neuropathy, peripheral neuropathy and myositis are rare. There has been significant progress in understanding the pathophysiology and treatment of the systemic disease, leading to improved outcomes, but there has been no randomised trial of treatment in the neurological disorder.
... Paresthesia, dysesthesia, numbness as sensory symptoms, and hemi/monoparesis and pyramidal signs as motor symptoms are other common manifestations (Benamour et al., 2006). Seizure in NBD is much rarer than in systemic lupus erythematosus (SLE) (Kutlu et al., 2015), (Dutra et al., 2011). Seizure can be due to parenchymal involvement or more commonly CVST (Kutlu et al., 2015). ...
Neuro-Behcet's disease (NBD) is defined as a combination of neurologic symptoms and/or signs in a patient with Behcet's disease (BD). Relevant syndromes include brainstem syndrome, multiple-sclerosis like presentations, movement disorders, meningoencephalitic syndrome, myelopathic syndrome, cerebral venous sinus thrombosis (CVST), and intracranial hypertension. Central nervous involvement falls into parenchymal and non-parenchymal subtypes. The parenchymal type is more prevalent and presents as brainstem, hemispheric, spinal, and meningoencephalitic manifestations. Non-parenchymal type includes CVST and arterial involvement. Perivascular infiltration of polymorphonuclear and mononuclear cells is seen in most histo-pathologic reports. In parenchymal NBD, cerebrospinal fluid (CSF) generally exhibits pleocytosis, increased protein and normal glucose. In NBD and CVST, CSF pressure is increased but content is usually normal. The typical acute NBD lesions in brain magnetic resonance imaging (MRI) are mesodiencephalic lesions. The pattern of extension from thalamus to midbrain provides a cascade sign. Brain MRI in chronic NBD usually shows brain or brainstem atrophy and/or black holes. The spinal MRI in the acute or subacute myelopathies reveals noncontiguous multifocal lesions mostly in cervical and thoracic lesions. In chronic patients, cord atrophy can also be seen. Brain MRI (particularly susceptibility-weighted images), MR venography (MRV) and computerized tomographic venography (CTV) can be used to diagnose CVST. Parenchymal NBD attacks can be treated with glucocorticoids alone or in combination with azathioprine. For patients with relapsing-remitting or progressive courses, shifting to more potent immunosuppressive drugs such as mycophenolate, methotrexate, cyclophosphamide, or targeted therapy is warranted. For NBD and CVST, immunosuppressive drugs with or without anticoagulation are suggested.
... KD, essentially an autoimmune vasculitis, was indicated in our results to have 8-fold increased risk of epilepsy than the references. This phenomenon echoes recent research that autoimmune disease have been implicated as causative factors of seizures and epilepsy [63,64]. In addition, when we investigated the association between KD and TS, no associated publication was discovered in PubMed. ...
Background:
Kawasaki disease (KD) is a common vasculitis of childhood in East Asia. The complications of KD ascribed to long-term cardiovascular sequelae are considerably diverse. Although studies have investigated neurodevelopmental problems following KD in the past few decades, they have reported inconsistent conclusions. This study investigated potential epilepsy and associated neurodevelopmental disorders (NDDs) following KD in Taiwanese children.
Methods:
We retrospectively analyzed the data of children aged < 18 years with clinically diagnosed KD from January 1, 2005, to December 31, 2015. These patients were followed up to estimate the prevalence of epilepsy and associated NDDs in comparison with the prevalence in general pediatric population in Taiwan and worldwide.
Results:
A total of 612 patients with an average age of 1.6 years were included. The prevalence of associated NDDs was 16.8% (n = 103/612) in the study group, which consisted of epilepsy, intellectual disability (ID), autism spectrum disorders, Tourette syndrome (TS), attention deficit hyperactivity disorder, (ADHD), and others. Moreover, children with KD had a higher prevalence of epilepsy and TS in both Taiwan and worldwide (epilepsy: 2.61% in the KD group vs 0.33% in Taiwan and 0.05-0.8% in worldwide, p < 0.05; TS: 2.77% in the KD group vs 0.56% in Taiwan and 0.3-1% in worldwide, p < 0.05). The prevalence of ID, ADHD, and developmental language disorders was not significantly different between our study patients and those in Taiwan or worldwide.
Conclusions:
Results revealed a higher prevalence rate of NDDs, especially epilepsy and TS, in Taiwanese children with KD than in the general pediatric population in Taiwan. However, these NDDs could be heterogeneous. Children diagnosed with KD were followed up because they had a higher risk of heterogeneous NDDs.
... Notably, among patients in the UK who were not ethnically from high-risk regions, neurologic involvement was more common (23%), and seizures were the more common feature of neuro-Behçet's (27%) (67). Similarly, in a Brazilian cohort of 178 Behçet's patients, 40 (22.5%) had neurological involvement, and epilepsy occurred in 7 (17%) of these patients, but only 4% of the overall sample (68). Tonic-clonic seizures predominate, but partial seizures, including epilepsia partialis continua, can occur (64,69,70). ...
Systemic autoimmune disorders affect multiple organ systems. Brain involvement commonly causes seizures, which may be the presenting symptom. Systemic lupus erythematosus, Sjorgren's syndrome, Wegener's granulomatosis, sarcoidsosis, celiac disease, Crohn's disease, Behcet's, and Hashimoto's encephalopathy are reviewed. Mechanisms underlying CNS pathology in systemic autoimmune disorders-and specifically factors predisposing these patients-are discussed, including vascular disease (e.g., prothrombotic state, anticardiolipin antibody, emboli, vasculitis), antineuronal antibodies, immune complexes, cytokines, metabolic disorders, infection, and therapy. Diagnostic and therapeutic strategies must be individualized for both the disorder and the patient. Systemic autoimmune disorders affect multiple organ systems and frequently involve the central and peripheral nervous systems. Seizures are among the most common neurological manifestation and occasionally can be the presenting symptom. There are many causes of seizures in systemic autoimmune disorders (Table 1), and the first clinical challenge is to determine not only the cause but also the significance of seizures. In some cases, they are clues to metabolic or infectious disorders or medication toxicity; in other cases, seizures herald a life-threatening progression of the underlying illness.
... Moreover, neuropsychological scores in BD and NBD groups were compared to a control group data since there was no normative data of the Brazilian population available. And as neurological manifestations in BD may vary according to ethnicity [4,8,[35][36][37][38], our results may be representative of our BD population only. ...
Unlabelled:
Neuro-Behçet's disease (NBD) presents cognitive and behavioral symptoms possibly explained by secondary dysfunction of frontal and temporal cortices due to subcortical damage, as NBD commonly involves the brainstem and basal ganglia. Nonetheless, there are reports of cognitive impairment in patients without neurological manifestations.
Objective:
To evaluate cognitive function in Behçet's disease (BD) patients with and without neurological manifestations and to analyze clinical variables associated with cognitive deficits.
Methods:
This is a cross-sectional study that compared healthy controls, BD patients without neurological manifestations and NBD patients. Each group comprised 24 participants. All participants underwent neuropsychological evaluation, Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory (BDI) application and brain MRI. Cumulative prednisone dose, years of education, and presence of white-matter lesions in brain MRI were recorded.
Results:
41.6% of BD and 41.6% of NBD patients showed impaired language and executive function, whereas visual memory was impaired only in NBD patients. Multiple logistic regression revealed that anxiety (OR 1.09 95% CI 1.03-1.16, p=0.003) and lower educational level (OR 0.62 95% CI 0.48-0.80, p<0.0001) were independently associated with cognitive impairment.
Conclusion:
Cognitive impairment occurs frequently in patients with BD independently of neurological manifestation. Low educational level and anxiety are risk factors for cognitive impairment in BD.
Systemic autoimmune disorders occur more frequently in patients with epilepsy than in the general population, suggesting shared disease mechanisms. The risk of epilepsy is elevated across the spectrum of systemic autoimmune disorders but is highest in systemic lupus erythematosus and type 1 diabetes mellitus. Vascular and metabolic factors are the most important mediators between systemic autoimmune disorders and epilepsy. Systemic immune dysfunction can also affect neuronal excitability, not only through innate immune activation and blood–brain barrier dysfunction in most epilepsies but also adaptive immunity in autoimmune encephalitis. The presence of systemic autoimmune disorders in subjects with acute seizures warrants evaluation for infectious, vascular, toxic and metabolic causes of acute symptomatic seizures, but clinical signs of autoimmune encephalitis should not be missed. Immunosuppressive medications may have antiseizure properties and trigger certain drug interactions with antiseizure treatments. A better understanding of mechanisms underlying the co-existence of epilepsy and systemic autoimmune disorders is needed to guide new antiseizure and anti-epileptogenic treatments. This review aims to summarize the epidemiological evidence for systemic autoimmune disorders as comorbidities of epilepsy, explore potential immune and non-immune mechanisms, and provide practical implications on diagnostic and therapeutic approach to epilepsy in those with comorbid systemic autoimmune disorders.
Background Kawasaki disease (KD) is a common vasculitis of childhood in East Asia. The complications of KD ascribed to long-term cardiovascular sequelae are considerably diverse. Although studies have investigated neurodevelopmental problems following KD in the past few decades, they have reported inconsistent conclusions. This study investigated potential epilepsy and associated neurodevelopmental disorders (NDDs) following KD in Taiwanese children. Methods We retrospectively analyzed the data of children aged
Background: Kawasaki disease (KD) is a common vasculitis of childhood in East Asia. The complications of KD ascribed to long-term cardiovascular sequelae are considerably diverse. Although studies have investigated neurodevelopmental problems following KD in the past few decades, they have reported inconsistent conclusions. This study investigated potential epilepsy and associated neurodevelopmental disorders (NDDs) following KD in Taiwanese children. Methods: We retrospectively analyzed the data of children aged
RESUME
Objectif
Quantifier la détérioration neurologique observée dans le konzo eu égard aux multiples déficiences incriminées dans sa pathogénie.
Méthodes
Une étude transversale a été entreprise auprès de 123 enfants konzo et 87 non-konzo (4-17 ans) en 2011 à Kahemba, Congo-Kinshasa. L’indice global de signes neurologiques du konzo (IGSNK) était étudié en relation avec le niveau socio-économique familial évalué par le HOME, les performances cognitives au KABC-II et motrices au BOT-2, les taux sériques des isoprostanes, oligoéléments, et l’albuminémie et triglyceridémie mesurés respectivement par LC-MS/MS, ICP-MS, et automate Piccolo. Les tests de χ2, de Mann-Whitney et Kruskal-Wallis, ou la corrélation r de Spearman ont été appliqués au seuil de signification de 0,05.
Résultats
L’augmentation de l’indice global des signes neurologiques du konzo était associée à la sévérité de la maladie (p < 0,001), le niveau socioéconomique familial (r = - 0,25 ; p < 0,001, la triglyceridémie (r = 0,55 , p = 0,001) et les 8,12-IsoProstaneF2-VI sériques (r = 0,33 , p= 0,06),), l’albuminémie (r = - 0,44 , p = 0,010 ) , la cuprémie ( r = - 0,36 , p= 0,048), le sélenium sérique (r = - 0,57, p = 0,001) ; en plus de l’habilité motrice globale (r = -0,861 ; p < 0,001) et l’indice global de fonctionnement cognitif (r = - 0,44 ; p = 0,002).
Conclusion
L’indice global des signes neurologiques du konzo paraît être un bon marqueur clinique de multiples déficiences (pauvreté socio-familiale, malnutrition, stress oxydatif) incriminées dans la sévérité du konzo.
Mots-clés : malnutrition, niveau socio-économique familial, stress oxydatif, konzo, intoxication cyanhydrique, troubles moteurs et cognitifs
ABSTRACT
Objective
To quantify the extent of neurological deficits in konzo in a context of multiple factors incriminated in its pathogenesis.
Methods
A cross-sectional study was carried out to assess 123 children with and 87 presumably healthy controls (4-17 years) in 2011 in kahemba, congo-kinshasa. A konzo global neurological index (KGNI) was constructed and assessed in relation to socio-economic status (assessed using the home questionnaire), cognitive and motor performances at the KABC-II and BOT-2, respectively; serum isoprostanes (measured by LC/MS-MS), trace elements (by ICP-MS), albumin and triglycerides (by automated Piccolo). The chi-square, Mann-Whitney and Kruskal-Wallis tests as well as the Spearman r coefficients were used at the 0.05 level of statistical significance.
Results
A higher KGNI was significantly associated with the severity of konzo (p < 0.001), poor socio-economic status (r = - 0.25, p < 0.001), elevated serum triglycerides (r = 0.55, p = 0.001), 8,12-isoprostane F2-VI (r = 0.33, p = 0.06), hypoalbuminemia (r = - 0.44, p = 0.010), low serum concentrations copper (r = - 0.36, p = 0.048) or selenium (r = - 0.57, p = 0.001);in addition to poor scores at the BOT-2 testing (r = -0.86; p < 0.001) and KABC-II testing for cognition (r = - 0.44; p = 0.002).
Conclusion
The konzo global neurological index appears to be a good clinical marker of disease susceptibility factors (poor socio-economic status, malnutrition, oxidative stress) incriminated in the severity of konzo.
Key-words: malnutrition, socio-economic status, oxidative stress, cyanide intoxication, neurocognition
Description
Introduction: La migraine est une maladie neurologique fréquente en population, source de handicap et classée 13ème des affections les plus handicapantes par l’OMS. L’objectif de cette étude était d’étudier la prévalence de la migraine à Titirou en 2017.
Méthodes: Il s’ est agi d’une étude transversale de type porte-à-porte menée sur 2065 sujets âgés de 18 à 65 ans. L’enquête a été effectuée sur une période de 4 mois allant du 10 avril au 05 août 2017. Les critères diagnostiques de l’International Headache Society (IHS) de 2013 ont servi de base pour le diagnostic de la migraine. Les informations sociodémographiques, le poids et taille et les données relatives à la fréquence et l’intensité des céphalées furent collectés. Les données ont été saisies, traitées et analysées grâce au logiciel Epi Info version 2.2. 0.165.
Résultats: Il y avait une prédominance masculine avec un sex-ratio de 1, 41. Les sujets étaient âgés de 18 à 65 ans avec une moyenne d’âge de 31, 87±8, 37ans. La prévalence des céphalées était de 63, 49%. La prévalence de la migraine à Titirou était de 3, 82%[IC95%:(3, 06%-4, 72%)](79 sur les 2065). Les facteurs associés à la migraine étaient l’âge (p= 0, 0026), le sexe (p= 0, 0001), le niveau d’instruction (p= 0, 0039), la profession (p< 10-4) et l’indice de masse corporelle (p< 10-4). L’intensité des céphalées était modérée dans 44, 30%, forte dans 51, 90%, extrêmement forte chez 3, 80% des sujets. La plupart des migraineux (78, 48%), avait moins de 5 crises par mois. La migraine avec aura représentait 49, 4%. Les auras les plus observées étaient les phosphènes (34, 18%), les scotomes (13, 92%) et l’aura sensitive (13, 92).
Background:
Neuro-Behçet Syndrome (NBS) is a severe chronic inflammatory vascular disease involving the Central Nervous System (CNS), and it is an invalidating condition with disability and a huge impact on quality of life. Recommendations on treatments for NBS include the use of disease-modifying therapies in general, although they are not supported by a systematic review of the evidence.
Objectives:
To assess the benefit and harms of available treatments for NBS, including biologics, colchicine, corticosteroids, immunosuppressants and interferon-alpha.
Search methods:
We searched the following databases up to 30 September 2014: Trials Specialised Register of The Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group, CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS, ORPHANET, Clinicaltrials.gov and World Health Organization (WHO) International Clinical Trials Registry Portal.
Selection criteria:
Randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective controlled cohort studies were eligible to assess the benefit. Patients over 13 years of age with a diagnosis of NBS. For assessment of harms, open-label extension (OLE), case-control studies, population-based registries, case-series and case-reports were additionally planned to be evaluated.
Data collection and analysis:
Selection of studies, data extraction and assessment of risk of bias were planned to be carried out independently by two review authors. Standard methodological procedures expected by The Cochrane Collaboration were followed. We planned to perform standard pair-wise meta-analyses for RCTs, and meta-analyses based on the adjusted estimates using the inverse-variance weighted average method for non-randomised studies (NRSs). We planned to present the main results of the review in a 'Summary of Findings' table using the GRADE approach.
Main results:
No RCTs, CCTs or controlled cohort studies on the benefit of the treatments for NBS met the inclusion criteria of the review. Only one potentially eligible study was identified, but it did not report sufficient details on the patient characteristics. The author of this study did not provide additional data on request, and therefore it was excluded. Hence, no studies were included in the present review. Since no studies were included in the assessment of benefit, no further search was performed in order to collect data on harms.
Authors' conclusions:
There is no evidence to support or refute the benefit of biologics, colchicine, corticosteroids, immunosuppressants and interferon-alpha for the treatment of patients with NBS. Thus, well-designed multicentre RCTs are needed in order to inform and guide clinical practice.
Systemic rheumatic disorders affect multiple organ systems. Seizures are among the most common neurological manifestation and occasionally can be the presenting symptom. This article reviews the literature on the mechanisms underlying seizures in systemic rheumatic disorders and predisposing factors, including vascular disease (e.g., prothrombotic state, anticardiolipin antibody, emboli, vasculitis), antineuronal antibodies, immune complexes, cytokines, metabolic disorders, infection, and therapy. Diagnostic and therapeutic strategies must be individualized for both the disorder and the patient.
Neurobehçet disease (NBD) is a rare complication of Behçet disease (BD) but with important burdens of morbidity and mortality. Little is known about this complication because there are no validated diagnostic criteria, and all the studies have small number of patients. The prevalence reported normally ranges between 5% and 15% and it is more frequent amongst men between 20 and 40 years old. The typical presentations include focal parenchymal lesions, vascular thrombosis, arterial vasculitis, and aseptic meningo-encephalitis.
We retrospectively studied medical histories of all patients admitted to the hospital and discharged from it with diagnosis of BD from January 1996 to September 2009. NBD was defined as having neurological and/or psychiatric symptoms with compatible abnormalities in MRI and/or cerebrospinal fluid and without another possible explanation for their symptoms.
Behcet disease was diagnosed in 25 patients and seven from these patients fulfilled our criteria of Neurobehcet disease (28%). Patients with NBD were significantly younger at the onset of their symptoms and had a significantly longer evolution until diagnosis and treatment compared to patients with non-Neuobehçet disease. Six presented a relapsing-remitting pattern, with a good outcome with corticosteroids.
As reported in previous studies, progressive course was less frequent, with only one case, and had a more aggressive disease. Brainstem involvement bears a poorer prognosis because it is linked with a progressive evolution. In our series, NBD complication was not that infrequent. It is very important to be highly suspicious of this possibility to start early a correct treatment.
To describe clinical and epidemiological data of Behçet’s disease (BD) in Brazil, we retrospectively reviewed records of all
patients seen between 2006 and 2007 at the BD outpatient clinic of University of Sao Paulo. One hundred and six patients fulfilled
the International Study Group for Behçet’s Disease diagnostic criteria and they were included in this study. There was a female/male
ratio of 2.2:1 and mean age at diagnosis was 31.9 ± 9.2years. In order of frequency, oral (100%) and genital ulcerations
(92.5%), pseudofolliculitis (59.4%), erythema nodosum (49.1%), ocular lesions (47.2%), and musculoskeletal complaints (35.8%)
were the most common manifestations. Blindness and major vessel involvement (18.2% vs. 5.5%, p = 0.038 and 27.3% vs. 9.6%, p = 0.019) were more frequent among male than female patients. We concluded that in Brazil, a South American country faraway
from the Silk Route, BD follows the same pattern exhibited on its usual endemic area.
The German Registry of Adamantiades-Behçet's disease was founded in 1990 in Berlin and it provides current data on the epidemiology, the clinical manifestations and the course of the disease in Germany on a continuous basis. A total of 218 patients, including 89 German and 100 Turkish patients, had been reported to the German Registry until October 1997. One hundred and ninety-six patients fulfilled the criteria of the Behçet's disease classification tree. The prevalence of the disease evaluated in Berlin-West was 1.68/100,000 in 1989 and had risen to 2.26/100,000 by 1994. The median age of onset was 25 years (range 5 to 66 years; German-Turks, ns). Juvenile disease was recorded in 6.9% of patients. The complete clinical picture according to the criteria of the International Study Group of Behçet's Disease developed in 15.5 months. The interval between onset of the disease and diagnosis was 35 months, which was significantly longer than the duration of the development of the complete clinical picture (p < 0.0001). The disease was diagnosed later in German (48.5 months) than in Turkish patients (25.5 months, p = 0.003). While German patients presented an equal male-to-female ratio, a male predominance was shown in Turkish patients (M:F 2.1:1, p = 0.022). Familial occurrence was detected in 2.0% of German and 15.9% of Turkish patients (p = 0.013). The frequencies of major clinical manifestations were: oral ulcers 99%, skin lesions 76%, genital ulcers 75%, ocular manifestations 59%, arthritis 59%, and positive pathergy test 52%. Clinical differences between German and Turkish patients were only found in the frequency of ocular lesions (48% vs. 66%, p = 0.025). Oral ulcers were with 72% the most common onset symptom of the disease followed by erythema nodosum (9%), uveitis (7%), arthritis (7%), genital ulcers (3%), superficial thrombophlebitis (2%) and papules/sterile pustules (2%). Uveitis and erythema nodosum as onset symptoms shortened the median interval to diagnosis to 1.5 and 15 months, respectively, while arthritis delayed diagnosis (43.5 months; p = 0.029). A severe course developed in 25% of the patients; irreversible retinal vasculitis to blindness in 15%, sterile meningoencephalitis in 8%, severe arthritis in 5%, hemoptysis in 2%, lethal outcome in 2% and bowel perforation in 1%. The relative risk of HLA-B5 positive German natives developing the disease. HLA-B5 was confirmed as a marker of severe prognosis. Cardiolipin autoantibodies were associated with cutaneous vasculitis and superficial thrombophlebitis was correlated with systemic vessel involvement.
A 25 year old right handed male shop assistant presented with seizures, visual problems, and malaise. The first symptoms were arthralgia and fatigue shortly followed by a bifrontal headache. A few days later he developed a visual disturbance that he described as peripheral blurred patches in both visual fields similar to the effect of staring into a bright light. About 2 weeks from the onset of symptoms he was driving when he had numerous episodes of deja vu and three episodes of a pungent sickly smell. He then lost consciousness and crashed his car into a public house without serious injury. An off duty nurse witnessed a generalised tonic-clonic seizure at the time. He was admitted to hospital and investigated but no diagnosis was made. The headache stopped completely in a month; the visual defects improved slightly but persisted. Six months later he had a relapse with recurrent headaches, pyrexia, and enlargement of the scotoma in the right eye and he was readmitted. He had had recurrent oral ulceration for 3 years and psoriasis since childhood, but no genital ulceration, red eyes, or venous thrombosis.
On examination he had a low grade pyrexia. General examination was otherwise normal with no …
Posterior reversible encephalopathy syndrome (PRES) is a recently proposed clinico-neuroradiological entity observed in a variety of clinical settings such as cyclosporin A (CsA) neurotoxicity. We report a 3.5-year-old Syrian boy in whom steroid-resistant focal segmental glomerulosclerosis (FSGS) was recently diagnosed. The patient remitted his nephrotic syndrome after 10 days of CsA administration. However, he shortly developed altered mental status, visual impairment, focal neurological deficits and seizures. We discontinued CsA that resulted in complete reversal of the patient's encephalopathical condition over a period of 4 months. We conclude that PRES should be suspected in immunosuppresed patients with kidney disease if they have a sudden episode of neurological symptoms.
The neurological complications of Behcet's syndrome have not been characterized with clarity. We present the clinical features, imaging characteristics and CSF findings of a series of 50 patients seen at the National Hospital for Neurology and Neurosurgery over the past 10 years. In this series, vascular complications had a low prevalence, whereas involvement of the brainstem was common; spinal cord lesions, hemisphere lesions and meningoencephalitis also occurred. Optic neuropathy, vestibulocochlear and peripheral nerve involvement occurred, but were rare. The prognosis for recovery was in general good, and the majority of those followed-up over a median of 3 years (range 1-19 years) had only single attacks. One-third of patients underwent further attacks, and four underwent progressive deterioration leading to disability. Factors suggesting a poor prognosis are repeated attacks, incomplete recovery, progressive disease course and a high level of CSF leucocytosis during acute attack. These data should be of help in the further definition of the clinical characteristics of this rare neurological disorder and in the planning of treatment trials.
Posterior reversible encephalopathy syndrome (PRES) is characterized by abnormalities in cerebral white matter and neurologic symptoms. It can be caused by immunosuppressive drugs or autoimmune diseases. We describe a case of PRES in a patient with collapsing focal glomeruloesclerosis (collapsing FGS) with complete recovery after withdrawal of cyclosporine (CSA).
A 27-year-old male presented a corticosteroid-resistant nephrotic syndrome secondary to collapsing FGS corticosteroid. Treatment with CSA was started after a nonresponding course of prednisone. Three weeks later, he developed an abrupt elevation of blood pressure (210/120 mmHg), with headaches, mental confusion, and generalized seizures. Magnetic resonance imaging (MRI) showed lesions suggestive of PRES. CSA was withdrawn, and a new MRI was normal after 2 months.
PRES is a rare syndrome that must be suspected in every patient presenting neurologic symptoms in the course of immunosuppression. It can be induced by CSA and is totally reversible when the drug is rapidly withdrawn.
Behçet's disease (BD) is a chronic multisystemic inflammatory disorder of unknown origin consisting of oral aphthous ulcers, ocular symptoms, skin lesions, and genital ulcerations. It has many features in common with systemic vasculitides and is more prevalent in countries along the ancient Silk route. Immune-mediated mechanisms play a major role in the pathogenesis of the disease, and inflammatory mediators are also involved. BD is not considered to be an autoimmune disorder, and the character of the disease needs to be clarified. Immunological aberrations in BD have been extensively studied by many investigators; genetic factors have been related to disease susceptibility, but their exact role in the development of disease is uncertain. Environmental factors such as infectious agents have also been implicated in the etiology of BD. However, the etiopathogenesis of the disease remains to be elucidated. Factors involved in the immunopathogenesis of BD with emphasis on the role of immunological aberrations are analyzed in this review.
"Neuro-Behcet's disease" (NBD) is the constellation of neurologic manifestations as a direct consequence of Behcet's disease usually confirmed by imaging studies and/or cerebrospinal fluid analysis. The authors propose a therapeutic algorithm for neuro-Behcet's disease based upon pathological, clinical, prognostic, and medico-economical issues based on available evidences. The authors divide anti-NBD armamentarium to first-line, second-line, and experimental drugs. These drugs should be administered hierarchically in treatment of parenchymal manifestations of neuro-Behcet's disease. First-line drug include corticosteroids, azathioprine, methotrexate, and cyclophosphamide. Second-line drugs are tumor necrosis factor (TNF) alpha blocking drugs, interferon-alpha, chlorambucil, and mycophenolate mofenil. Experimental drugs include other "targeted therapies" than anti-TNF antibodies, tolerization therapy and stem cell transplantation. Cerebral venous sinus thrombosis associated with Behcet's disease should be treated by short-term corticosteroids and anticoagulation with or without immunosuppressive drugs.
The type and frequency of neurological manifestations of Behçet's disease (BD) vary with ethnicity. We analyzed the neurological manifestations of BD in Japanese patients. All patients undergoing treatment at one of the two Yokohama City University hospitals from July 1991 to December 2007 and who fulfilled the Japanese criteria for BD revised in 1987 were studied retrospectively by chart review. Patients had been neurologically assessed by neurologists. We recorded neurological signs and symptoms, magnetic resonance imaging or computed tomography findings, and results of cerebrospinal fluid examinations from the records of each patient. We studied 412 patients with BD, of whom 54 (13%) had neurological involvement (neuro-Behçet's disease: NB). NB patients included a significantly higher proportion of males (61%) than non-NB patients (42%, P = 0.009). The majority of patients (n = 38, 70%) had acute parenchymal NB, 15 (28%) had chronic progressive parenchymal NB, and 1 (2%) had the non-parenchymal type. Headache and fever were more frequently reported by patients with acute parenchymal NB. Personality changes, sphincter disturbances, involuntary movements, and ataxia occurred predominantly in patients with chronic progressive parenchymal NB. Lesions were distributed throughout the CNS, but mainly in the brainstem, white matter, and basal ganglia. Analysis of end-point clinical outcomes revealed a poor prognosis for patients with chronic progressive NB. In Japan, most NB patients have the parenchymal type, and male gender is a predisposing factor. Because of the unfavorable prognosis associated with chronic progressive NB, development of effective therapies are urgently needed.
Behçet's Syndrome (BS) is a multi-system, vascular-inflammatory disease of unknown origin, involving the nervous system in a subgroup of patients. The growing clinical and imaging evidence suggests that primary neurological involvement in BS may be subclassified into two major forms: the first one, which is seen in the majority of patients, may be characterized as a vascular-inflammatory central nervous system (CNS) disease, with focal or multifocal parenchymal involvement mostly presenting with a subacute brainstem syndrome and hemiparesis; the other, which has few symptoms and a better neurological prognosis, may be caused by isolated cerebral venous sinus thrombosis and intracranial hypertension. These two types rarely occur in the same individual, and their pathogenesis is likely to be different. Isolated behavioral syndromes and peripheral nervous system involvement are rare, whereas a nonstructural vascular type headache is relatively common and independent from neurological involvement. Neurologic complications secondary to systemic involvement of BS such as cerebral emboli from cardiac complications of BS and increased intracranial pressure due to superior vena cava syndrome, as well as neurologic complications related to BS treatments such as CNS neurotoxicity with cyclosporine and peripheral neuropathy with the use of thalidomide or colchisin are considered as secondary neurological complications of this syndrome. As the neurological involvement in this syndrome is so heterogeneous, it is difficult to predict its course and prognosis, and response to treatment. Currently, treatment options are limited to attack and symptomatic therapies with no evidence for the efficacy of any long term preventive treatment.
Behçet's disease (BD) is a multisystem relapsing inflammatory disorder of unknown cause. In neuro-BD (NBD), the CNS can be involved in one or both of two ways: first, and most commonly, through the development of an immune-mediated meningoencephalitis, which predominantly involves the brainstem, but can also involve the basal ganglia, thalamus, cortex and white matter, spinal cord, or cranial nerves; and second, as a consequence of thrombosis within the dural venous sinuses. Headache is a common symptom in BD and does not necessarily indicate CNS involvement. Peripheral nervous system involvement is rare. New treatment options have recently become available, which have led to an improvement in morbidity after meningoencephalitis. Most of the reported studies on NBD are retrospective. Collaborative prospective studies of the natural history of the disease, particularly the nature and treatment of progressive neurological disease, and evidence-based studies of treatment are needed.
A thirty-six year old male with a sixteen month history of a progressive neurological disorder had Behcet's disease. His initial electroencephalogram showed periodic lateralizing epileptiform discharges (PLEDs). The electroencephalographic changes in this disorder have not been described in detail in the American literature. The review of world publications in this matter disclosed that there is no specific EEG pattern in this condition, and that electroencephalographic changes are mainly related to the side of the lesion and have no prognostic value.
Animal stroke models demonstrate excitatory amino acid (EAA) release in ischemic tissue, as measured by microdialysis. Currently glutamate antagonist drugs are being developed to protect brain tissue after ischemic events. However, the role of EAAs in human occlusive stroke is not well known. We therefore measured glutamate and aspartate release in a patient after occlusive stroke.
We describe a case of occlusive stroke in a 50-year-old man. A partial temporal lobectomy was done to remove infarcted tissue and to prevent brain stem compression as well as uncal herniation. A microdialysis probe was placed into the cortex to measure EAAs. Massively increased levels of glutamate and aspartate were detected in the extracellular fluid in this patient (> 300 times normal levels 6 days after infarction).
These findings indicate that EAAs are tremendously increased in brain tissue after occlusive stroke. The time course of the release of EAAs is much longer than animal studies have suggested previously. Administration of EAA antagonists to patients with ischemic stroke may therefore be beneficial.
A rare case of neuro-Behçet disease with diffuse demyelination and gliosis of the frontal white matter is reported clinico-pathologically. The disease began with genital ulcer and recurrent oral aphthosis when the patient was 42 years of age. There was erythema, moderate fever, CSF (cerebrospinal fluid)-pleocytosis and elevated CSF-globulin. He was diagnosed as having neuro-Behçet disease and treated with prednisolone. He gradually became euphoric, disinhibited, indifferent and demented. His cranial CT showed diffuse low density areas in the bilateral frontal white matter. He became bedridden, akinetic mute and died from respiratory dysfunction 3 1/2 years after onset. The following neuropathological findings were observed: 1) Moderate demyelination and gliosis was present mainly in the frontal and parietal white matter. 2) There were many micro-spongious necrotic foci in the gray and white matters of the cerebrum, basal ganglia, thalamus, midbrain and pons, some of which were accompanied by gliosis. 3) From 1/2 to 1/3 of all micro-necrotic foci in the frontal white matter were old and accompanied by gliosis. The white matter containing numerous micro-necrotic foci had myelin pallor and gliosis. 4) There was neither micro-necrosis nor gliosis in the occipital lobe. The pathogenetic correlation of white matter lesions with primary and secondary circulatory disturbances is discussed.
Behçet's disease is a multisystem disease that is rare in the United States.
The purpose of our study was to assess the characteristics and treatment of a series of patients with Behçet's disease in the United States.
A retrospective clinical review of 25 patients with Behçet's disease was performed, and histopathologic findings and therapeutic modalities were reviewed.
All patients had oral and genital aphthae, and 22 of 25 patients had cutaneous lesions consistent with Behçet's disease. Eight of 25 patients had relatively severe systemic disease. Nine of 14 biopsy specimens showed a neutrophilic vascular reaction. Our therapeutic "ladder" included aggressive topical and intralesional corticosteroids, colchicine, dapsone, methotrexate, and thalidomide; we reserved systemic corticosteroids and immunosuppressive medications for severe ocular or severe systemic disease.
This series of patients with Behçet's disease was characterized by patients with prominent mucocutaneous involvement and a low prevalence of ocular involvement. These findings may be attributed to patient selection from referral to a university dermatology clinic.
Behçet disease (BD) is a multisystem vasculitis of unknown origin in which neurologic involvement has been reported in the range of 5% to 10% in large series. Reports on clinical and radiologic aspects of neuro-Behçet syndrome (NBS) are in general limited in number. Our purpose was to determine the MR patterns in patients with NBS who had neural parenchymal involvement and to correlate our findings with possible vascular pathophysiology.
The MR images of 65 patients with NBS and neural parenchymal involvement were reviewed. In a subgroup of patients who had serial MR studies, we evaluated the anatomic-radiologic location and distribution of the lesions and whether they corresponded to any vascular territory, and studied their extension, enhancement patterns, and temporal course.
The most common imaging finding in NBS patients who had neural parenchymal involvement was a mesodiencephalic junction lesion with edema extending along certain long tracts in the brain stem and diencephalon in 46% of the patients. The next most common location of involvement was the pontobulbar region, seen in 40% of the cases. Three primary cervical spinal cord lesions and one case of isolated optic nerve involvement were observed.
The parenchymal distribution of lesions in NBS appears to support the hypothesis of small-vessel vasculitis; mainly, venular involvement. The anatomic distribution of intraaxial veins of the CNS explains the predominant involvement of the brain stem structures observed in our patients. This pattern of lesion distribution might help to differentiate NBS from other vasculitides as well as from the inflammatory-demyelinating diseases of the CNS, such as multiple sclerosis.
The neurological complications of Behçet's syndrome have not been characterized with clarity. We present the clinical features, imaging characteristics and CSF findings of a series of 50 patients seen at the National Hospital for Neurology and Neurosurgery over the past 10 years. In this series, vascular complications had a low prevalence, whereas involvement of the brainstem was common; spinal cord lesions, hemisphere lesions and meningoencephalitis also occurred. Optic neuropathy, vestibulocochlear and peripheral nerve involvement occurred, but were rare. The prognosis for recovery was in general good, and the majority of those followed-up over a median of 3 years (range 1-19 years) had only single attacks. One-third of patients underwent further attacks, and four underwent progressive deterioration leading to disability. Factors suggesting a poor prognosis are repeated attacks, incomplete recovery, progressive disease course and a high level of CSF leucocytosis during acute attack. These data should be of help in the further definition of the clinical characteristics of this rare neurological disorder and in the planning of treatment trials.
In order to define the patterns of neurological involvement in Behçet's disease and to assess prognostic factors, 558 files of the neuro-Behçet out-patient clinic were reviewed. Those patients without any evidence of objective neurological involvement as well as the patients with other possible explanations for the neurological picture, and cases not fulfilling the criteria for Behçet's disease were excluded. The remaining 200 cases (155 male, 45 female) were evaluated: 162 had parenchymal CNS involvement (brainstem or 'brainstem +' involvement in 51%, spinal cord involvement in 14%, hemispheric involvement in 15% and isolated pyramidal signs in 19%) while 38 had secondary or non-parenchymal CNS involvement. In the first group the most common findings were pyramidal signs, hemiparesis, behavioural changes and sphincter disturbance, whereas in the second group the syndrome of raised intracranial pressure due to dural sinus thrombosis was the main clinical manifestation. In 60% of the cases with parenchymal involvement, CSF was hypercellular and/or had an elevated protein level, whereas in cases with non-parenchymal involvement the CSF was usually normal except for the elevated pressure. In more than half of the patients with parenchymal involvement, MRI showed brainstem and/or basal ganglion lesions. Forty-one per cent of the cases had a course with at least one attack and remission, another 28% also had attack(s) but showed secondary progression, 10% had primary progression and 21% had silent neurological involvement. Survival analysis was performed in patients who had at least a 3-year duration of neurological disease. Parenchymal involvement, elevated protein and/or pleocytosis in the CSF, 'brainstem +' type involvement, primary or secondary progressive course and relapse during steroid tapering were all associated with a poorer prognosis.
A diagnostic scheme for epileptic seizures and epilepsies with five levels or Axes is proposed (1, ictal semiology; 2, seizure type[s]; 3, epilepsy syndrome; 4, etiology, and 5, resulting impairment). A standardized Glossary of Descriptive Terminology is used for the description of the ictal semiology and the description of seizure types is derived from a list of accepted seizure types constructed by the Task Force. If possible, the syndromic diagnosis follows according to a list of accepted epilepsy syndromes as well as syndromes in development provided by the Task Force. Regarding etiology another list or classification of diseases frequently associated with epileptic seizures or syndromes is provided. The (optional) designation of a resulting impairment will be derived from the WHO International Classification of Functioning and Disability. In addition, the use of some diagnostic terms is discouraged or they are replaced by others (e.g. simple and complex partial seizures", partial" and localization related syndromes", convulsive" and convulsion"), the meaning of other terms is clarified (cryptogenic" = probably symptomatic") and some new concepts are proposed (e.g. epileptic disease" with a single, specific etiology or epileptic encephalopathy" as condition, in which the epileptic processes themselves lead to cerebral dysfunction). It is emphasized that this proposal is not a new classification of seizures and epilepsies or epilepsy syndromes. The proposed scheme should lead to an updated and uniformed use of the diagnostic vocabulary in the preparation of a future new classification or rather multiple classifications for different purposes (e.g. for teaching and research purposes or clinical trials). It is flexible and will be periodically changed and updated in the future as needed.
Stroke is the major cause of acquired epilepsy. The mechanisms of ischemia-induced epileptogenesis are not understood, but glutamate is associated with both ischemia-induced injury and epileptogenesis in several models. The objective of this study was to develop an in vitro model of epileptogenesis induced by glutamate injury in hippocampal neurons as observed during stroke.
Primary hippocampal cultures were exposed to 5 micromol/L glutamate for various durations. Whole-cell current clamp electrophysiology was used to monitor the acute effects of glutamate on neurons and chronic alterations in neuronal excitability up to 8 days after glutamate exposure.
A single, 30-minute, 5-micromol/L glutamate exposure produced a subset of neurons that died and a larger population of injured neurons that survived. Neuronal injury was characterized by prolonged reversible membrane depolarization, loss of synaptic activity, and neuronal swelling. Surviving neurons manifested spontaneous, recurrent, epileptiform discharges in neural networks characterized by paroxysmal depolarizing shifts and high-frequency spike firing that persisted for the life of the culture.
This study demonstrates that glutamate injury produced a permanent epileptiform phenotype expressed as spontaneous, recurrent epileptiform discharges for the life of the hippocampal neuronal culture. These results suggest a novel in vitro model of glutamate injury-induced epileptogenesis that may help elucidate some of the mechanisms that underlie stroke-induced epilepsy.
Behçet's disease (BD) is a chronic relapsing multisystem disorder. While most frequently occurring around the Mediterranean and in Japan, isolated cases of BD have been reported in Africa south of the Sahara and in the Caribbean. The aim of this study was to describe our experience of BD in Guadeloupe (French West Indies) where the presence of the disease has not been reported previously. We analysed retrospectively the charts, and clinical and imaging features of patients native to Guadeloupe who were diagnosed with neurological manifestations of BD between 1989 and 1999. In our series of 13 cases, seven had neurological involvement. Neurological manifestations included meningoencephalitis or meningoencephalomyelitis in four cases, cerebral venous thrombosis in one case and peripheral neuropathy in two cases associated with myositis in one. Patients received treatment with colchicine (n=7), corticosteroids (n=6), immunosuppressive therapy (azathioprine and/or cyclophosphamide; n=4), acetylsalicylic acid (n=2) and oral anticoagulation for venous thrombosis (n=1). Long-term sequelae occurred only in patients with recurrent neurological disease. This study suggests that the frequency of BD in this Afro-Caribbean population is higher than this reported in Caucasian populations. Meningoencephalitis is associated with a poor prognosis while other patients achieved recovery.
To outline the clinical characteristics of seizures in our large series of Behçet disease (BD) patients with neurologic involvement.
All files of 223 patients with neuro-BD were evaluated retrospectively, and the group with clearly documented seizures was included in the current study. Clinical characteristics, EEG, neuroimaging and cerebrospinal fluid findings were reevaluated, and the seizures were classified according to the new proposed criteria of the International League Against Epilepsy. On excluding the patients in whom the seizures were due to possible seizure-provoking factors, the seizures that appeared during a neurologic exacerbation were noted.
Seizures were seen in 10 (4.48%) of 223 patients. There were one female and nine male patients. In five of the patients, seizures occurred during neurologic exacerbation. Therefore, the actual prevalence of seizures due to BD in our group is 2.2%. In the remaining five patients, the seizures were not related to neurologic BD attacks, but probably were due to some seizure-provoking factors. The predominating seizure type was generalized tonic-clonic convulsions accompanied by focal motor seizures. It is notable that four patients died 1-5 years after the onset of the seizures.
Our study showed that seizures are rare in BD. As the seizures due to some interventions and drugs are as frequent as neuro-BD-related seizures, seizure-provoking factors must be considered before attributing them to the pathogenetic mechanism of BD. The occurrence of seizures seems to be associated with a high mortality rate.
Behcet's disease is a multisystem vasculitis. Its neurologic complications include different syndromes. The purpose of this investigation was to study the prevalence of neurologic manifestations among patients with Behcet's disease and to determine the frequency of different symptoms, signs, and syndromes in neuro-Behcet's disease. Ninety-six consecutive patients who were referred to the Behcet's Disease Clinic in Shiraz (southern Iran) were interviewed and thoroughly examined. Psychiatric evaluation, CSF analysis, electroencephalography, electrodiagnostic studies, and neuroradiologic imaging (preferably MRI) were performed in appropriate cases. Six patients (6.3%) had definite neuro-Behcet's disease. They were 4 males and 2 females (mean age 37.5 years). In 2 patients Behcet's disease had not been diagnosed before. The most frequent symptoms of neuro-Behcet's disease were headache (83.3%), paresthesia (83.3%), unsteadiness (66.7%), diplopia (66.7%), and weakness (50%). The most frequent signs were gait abnormalities (66.7%), sensory abnormalities (66.7%), ophthalmoplegia (50%), cerebellar ataxia (50%), and hemiplegia (50%). The most common syndrome was brain-stem+ type (50%). Subacute onset and relapsing-remitting course were the most common temporal patterns. Neurological manifestation is a relatively less frequent complication of Behcet's disease but it produces severe disabilities. It must be considered in differential diagnosis of multiple sclerosis.
Several analyses of the neurological features of Behçet's disease (BD) have concluded that there are significant racial differences in its clinical expression. Other series, however, failed to elicit such differences. We aimed to describe in this retrospective survey the frequency, nature and relationship to systemic disease of the neurological features in a cohort of BD patients of Caucasian origin. We searched hospital records from nine District General or Regional Centre hospitals in south-west Great Britain and identified 22 individuals of Caucasian ethnic origin with neuro-BD, with a mean of 10 years follow-up per patient - the largest 'western' case series with the longest period of follow-up reported. We found that presentation with neurological features was commoner in our patients (23%) than Middle Eastern series (3-10%). Seizures (27%) were likewise commoner (0-5%), as was optic neuritis (9% compared with 1-2%). Two patients developed movement disorders (chorea and parkinsonism), which have only been rarely reported. Of further clinical significance, we noted that non-neuropsychiatric features: oral ulceration, intraocular inflammation and skin lesions - were virtually always present or exacerbated during neurological complications. Ethnicity--or conceivably environment--may play a significant role in the manifestation of neurological BD.
Behçet's disease (BD) is a multisystemic disease of unknown etiopathogenesis with various clinical features including manifestations from central nervous system involvement. We report the case of a patient presented with a 20-year history of BD and a 10-year history of epileptic seizures refractory to various antiepileptic drugs. Under systemic treatment with interferon-alpha 2a (IFN-alpha) a complete remission of the cutaneous manifestations and a seizure-free state were achieved. The impressive therapeutic response of both the seizures and the non-neurological manifestations to IFN-alpha was also observed upon re-administration of this cytokine subsequent to a severe BD relapse. In view of this response and the lack of any other obvious etiology of the seizures in our patient, it seems reasonable to consider them as being the sole manifestation of neuro-BD. The patient is presently completing a 40-month seizure-free follow-up, despite withdrawal of all antiepileptic drugs for the last 35 months. Further studies on large numbers of patients are now warranted to define the therapeutic efficacy and safety of IFN-alpha in neuro-BD and particularly in neuro-BD-related epileptic seizures.
International Study Group for Behcet's Disease. Criteria for diagnosis of Behçet's disease
International Study Group for Behcet's Disease. Criteria for diagnosis of Behçet's
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