Bands In CSF Research Articles

Chronic Relapsing Inflammatory Optic Neuropathy: A Differential Diagnosis from Multiple Sclerosis (P02.151)

Objective: We report 3 cases of possible CRION (chronic relapsing inflammatory optic neuritis), review the literature and discuss its differential diagnoses. Background Currently there is no population-based data on the natural history, prognosis and treatment plan for CRION (Kidd et al Brain 2003). Optic neuritis (ON) is the initial presentation in 20% of cases of MS. Recurrent ON affecting either eye, excluding cases of ON appearing in systemic disease, occurs in 20 to 36% of all cases with a documented first attack with ON. Relapsing-remitting inflammatory optic neuropathy is rare, often bilateral, and typically steroid responsive. Design/Methods: We reviewed 3327 patients in the MS Clinic in London, Ontario seen in the last decade. specifically searched for clinically isolated syndrome (CIS) and ON cases to be included in this review. Data were collected regarding demographics, past medical history, history of present illness, brain MRI scans and laboratory tests. We used the McDonald 2005 diagnostic criteria for MS and the Kidd et al 2003 definition for CRION. Results: We found 3 cases compatible with the definition CRION. One male and 2 females, caucasian, ages 31 to 46 years old, followed for over 12 months and up to 10 years. Oligoclonal bands in CSF were negative. Brain and spine MRI did not meet diagnostic criteria for MS and did not reveal any other pathology. We ruled out Leber9s hereditary optic neuropathy, Neuromyelitis optica, Vitamin B12 deficiency, Sarcoidosis, Rheumatological or connective tissue diseases, and Multiple Sclerosis. Conclusions: CRION should be considered in the differential diagnosis of MS, however, it is a diagnosis of exclusion, distinguished from demyelinating disease, granulomatous, infectious, and other inflammatory or infiltrative ON. Steroid-sparring agents should be considered in the long term while pulse steroids appear to be the treatment of choice for relapses until further evidence is available. Disclosure: Dr. Di Guglielmo has nothing to disclose. Dr. Kremenchutzky has received personal compensation for activities with MS Society of Canada, the End MS Research and Training Network, the Research Scientific Foundation of the MS Society of Canada, and the Canadian Institute of Health Research, Bayer Pharmaceuticals, Biogen Idec, Serono, Inc., Genzyme Corporation, Novartis, Sanofi-Aventis Pharmaceuticals, and Teva Neuroscience as a speaker, researcher and/or consultant. Dr. Kremenchutzky has received research support from MS Society of Canada, Bayer Pharmaceuticals Corporation, Biogen Idec, Serono, Inc., Teva Neuroscience, Genetech, Inc., and Novartis.

Encefalomielitis aguda diseminada: análisis epidemiológico, clínico, analítico y evolutivo en 16 pacientes

IntroductionAcute disseminated encephalomyelitis (ADEM) is a rare paediatric disease of autoimmune origin. The aim of this study is to estimate its impact in our area over the past 10 years and to analyse the clinical, laboratory and radiological presentation, as well as study the response to treatment and outcome. Patients and methodsA retrospective analysis of cases diagnosed with current ADEM criteria. The age and month of the year at onset, sex, family history of demyelination, initial symptoms, disease or previous vaccination, CSF features, serology, PCR for herpes virus group in blood and CSF, oligoclonal bands in CSF, EEG and neuroimaging features of the skull by MRI, the type of treatment received and the response were recorded on each of the patients diagnosed. ResultsThere were 16 patients, with a mean age of 5.6 years. Male/female: 11/5, with a dominant debut in the colder months of the year, predominantly gait disorder, changes in consciousness and seizures. The radiology by MRI showed a predominance of multiple lesions in the same T2 stage, in deep white matter and lesions in deep grey matter. There were no in blood parameters and the CSF was normal in half of the cases. The origin was determined in 7 cases. ConclusionsThe annual incidence in children under 14 years was estimated at 0.64/100,000. The clinical and radiological findings were the basis of diagnosis. The human herpes virus 6 was involved in 4 cases. Most patients recovered completely.

P06.16 Clinical manifestations of the autoimmune process of central nervous system

Background: Pediatric infection triggered Autoimmune Neu¬ropsychiatric Disorders are described in the literature since 1.998. Autoimmune limbic encephalitis is recognized as a precipitating factor of onset temporallobe seizures. Aim: two case reports of children with autoimmune neuropsychiatric disorders. First case: K.L., 13 years old girl was hospitalized for the third cime because she had fever, ataxia, psychomotor seizures, bizarre gait and abnorrnai choreiforrn movements, catatonia, dysarthric speech and communication only in German .anguage with often changes in mood and hallucinations. Previous hospitalization was two weeks earlier because she had a painful right mastoid. First hospitalization was two years earlier because of right mastoids infection and right retrobulbar neuritis. Now the EEG showed the focus of the slow waves on the right temporal, and later on both sides in temporoparietal region ; oligodonal bands in CSF were positive ; MS CT of pyramids showed chronic inflammatory changes right and psychological testing showed deficits in cognitive functions. She was treated with antibiotics, steroids, benzodiazepines and carbamazepine. The patient underwent exploratory antrotomy of the right ear. After that she had started to recover. Second case: In l6-year-old girl non-paraneoplastic lim¬bic encefalitis was diagnosed. Immune thrombocytopenia manifested in chronic form had been diagnosed 11 years earlier. She had complex partial seizures and developed behavioral disturbances: anxiety, feeling of unreality, auditory hallucinations and insomnia. EEG showed frontal fast beta activity. MRI scans demonstrated a temporal swelling. Cere¬brospinal fluid showed pleocytosis and positive oligodonal bands. The serologycal tests for neurotropic viruse were negative. Immunomodulation therapy was followed by an improvement of clinical status.

Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study

HLA-DRB1*15 genotype, previous infection with Epstein-Barr virus, and vitamin D insufficiency are susceptibility factors for multiple sclerosis, but whether they act synergistically to increase risk is unknown. We aimed to assess the contributions of these risk factors and the effect of established precursors of multiple sclerosis, such as brain lesions on MRI and oligoclonal bands in CSF at the time of incident demyelination, on development of multiple sclerosis in children. In our prospective national cohort study, we assessed children who presented with incident CNS demyelination to any of the 16 paediatric health-care facilities or seven regional health-care facilities in Canada. We did univariate and multivariable analyses to assess contributions of HLA-DRB1*15, Epstein-Barr virus, vitamin D status, MRI evidence of brain lesions, and CSF oligoclonal bands as determinants of multiple sclerosis. We used classification and regression tree analyses to generate a risk stratification algorithm for clinical use. Between Sept 1, 2004, and June 30, 2010, we screened 332 children of whom 302 (91%) were eligible and followed-up for a median of 3·14 years (IQR 1·61-4·51). 63 (21%) children were diagnosed with multiple sclerosis after a median of 127 days (99-222). Although the risk of multiple sclerosis was increased with presence of one or more HLA-DRB1*15 alleles (hazard ratio [HR] 2·32, 95% CI 1·25-4·30), reduced serum 25-hydroxyvitamin D concentration (HR per 10 nmol/L decrease 1·11, 1·00-1·25), and previous Epstein-Barr-virus infection (HR 2·04, 0·99-4·20), no interactions between these variables were detected on multivariate analysis. Multiple sclerosis was strongly associated with baseline MRI evidence of one or more brain lesion (HR 37·9, 5·26-273·85) or CSF oligoclonal bands (6·33, 3·35-11·96), suggesting established disease. One patient diagnosed with multiple sclerosis had a normal MRI scan, and therefore sensitivity of an abnormal MRI scan for multiple sclerosis diagnosis was 98·4%. Risk of multiple sclerosis in children can be stratified by presence of HLA-DRB1*15 alleles, remote Epstein-Barr virus infection, and low serum 25-hydroxyvitamin D concentrations. Similar to previous studies in adults, brain lesions detected on MRI and CSF oligoclonal bands in children are probable precursors to the clinical onset of multiple sclerosis. Children with a normal MRI are very likely to have a monophasic illness. Canadian Multiple Sclerosis Scientific Research Foundation.

Brain atrophy and lesion load are related to CSF lipid-specific IgM oligoclonal bands in clinically isolated syndromes

The objective of this work is to study the relationship between the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in CSF, with both T2 lesion volume (T2LV) accumulation and brain atrophy (percentage change of brain volume-PCBV-and brain parenchyma fraction-BPF) in patients with clinically isolated syndromes (CIS) suggestive of demyelination. Twenty-four CIS patients were included in this prospective study. IgG oligoclonal bands (OCGB) and LS-OCMB were determined in paired serum and CSF samples within 3months since clinical onset. Brain MRI studies were scheduled at baseline, 3months, first and second years after CIS onset. Differences in T2LV, PCBV and BPF between CIS patients according to the type of OCB were studied. Nine patients had no OCB; 15 had only OCGB, and seven had OCGB + LS-OCMB present in the CSF. LS-OCMB were associated with greater T2LV in all scheduled MRI studies. At the end of follow-up (year2), it was threefold higher in patients with these antibodies than in those without LS-OCMB (3.95cm(3) vs. 1.36cm(3), p = 0.001). At that point, brain atrophy was also higher in patients with LS-OCMB (BPF, 0.73 in LS-OCMB+ patients vs. 0.76 in negative ones, p = 0.03). The rate in brain atrophy was higher in the first group of patients as well. Considering only patients with OCGB, the presence of LS-OCMB was also related to greater T2LV, T2LV increase and a trend towards higher atrophy rate. The presence of LS-OCMB in the first event suggestive of demyelination is related to an early increase in lesion load and brain atrophy. These data are in line with prospective studies showing the clinical prognostic value of LS-OCMB.

Analysis of the pain in multiple sclerosis patients

Introduction Despite pain being a disabling symptom in patients with multiple sclerosis (MS), its prevalence and characteristics are not well established. The aim of this study is to describe the characteristics and prevalence of pain in patients with MS, and to assess the associated clinical variables and radiological findings. Methods We prospectively studied patients with MS. A structured questionnaire which evaluated depression symptoms, type of pain, location, intensity (defined according to a visual analogue scale (VAS) as severe (VAS 7–10), moderate (VAS 4–6) and mild (VAS 0–4), and pain therapy was recorded in patients who referred to pain at the time of interview. Protocol variables were demographic data, MS clinical forms (remitting-relapsing, progressive-secondary and progressive-primary), neurological dysfunction (defined according to EDSS scale), symptoms at onset, attack frequency, illness duration, disease modifying treatment, fatigue, spasticity, oligoclonal bands in CSF, visual evoked potentials, depression symptoms (Hamilton test) and presence of lesions in spinal cord MRI. Results A total of 134 MS patients were included, and MRI was performed on 105 of them. Pain was reported by 74 (55%) patients and was most frequently neuropathic, located in limbs, severe and burning/spiky. Of these 28 (38%) received therapy for their pain, based predominantly in anti-inflammatory drugs. Patients with pain had a worse functional state (EDSS score, 4.5 [3–6] vs 1.5 [1–2], p < 0.001), higher number of relapses (7.13 ± 3.4 vs 3.75 ± 2.9, p < 0.001), progressive forms of MS (86.7% vs 13.3%, p < 0.001), depression (91.9% vs 8.1%, p < 0.001), spinal cord involvement at onset (79.2% vs 20.8%, p = 0.009), spinal cord lesions by MRI (84.3% vs 15.7%, p < 0.001) and longer duration of disease (14.6 ± 7.8 vs 8.43 ± 5.9 months, p < 0.001). In a logistic regression model, the presence of lesions in spinal cord MRI (OR 3.5 [1.5–24.5]) and higher EDSS score (OR 1.7 [1.1–2.7]) were independently associated with pain. Conclusions Pain is a frequent disabling symptom in MS and is associated with disability and spinal cord lesions.

Análisis del dolor en pacientes con esclerosis múltiple

Introduction Despite pain being a disabling symptom in patients with multiple sclerosis (MS), its prevalence and characteristics are not well established. The aim of this study is to describe the characteristics and prevalence of pain in patients with MS, and to assess the associated clinical variables and radiological findings. Methods We prospectively studied patients with MS. A structured questionnaire which evaluated depression symptoms, type of pain, location, intensity (defined according to a visual analogue scale (VAS) as severe (VAS 7-10), moderate (VAS 4-6) and mild (VAS 0-4), and pain therapy was recorded in patients who referred to pain at the time of interview. Protocol variables were demographic data, MS clinical forms (remitting-relapsing, progressive-secondary and progressive-primary), neurological dysfunction (defined according to EDSS scale), symptoms at onset, attack frequency, illness duration, disease modifying treatment, fatigue, spasticity, oligoclonal bands in CSF, visual evoked potentials, depression symptoms (Hamilton test) and presence of lesions in spinal cord MRI. Results A total of 134 MS patients were included, and MRI was performed on 105 of them. Pain was reported by 74 (55%) patients and was most frequently neuropathic, located in limbs, severe and burning/spiky. Of these 28 (38%) received therapy for their pain, based predominantly in anti-inflammatory drugs. Patients with pain had a worse functional state (EDSS score, 4.5 [3-6] vs 1.5 [1-2], p < 0.001), higher number of relapses (7.13 ± 3.4 vs 3.75 ± 2.9, p < 0.001), progressive forms of MS (86.7% vs 13.3%, p < 0.001), depression (91.9% vs 8.1%, p < 0.001), spinal cord involvement at onset (79.2% vs 20.8%, p = 0.009), spinal cord lesions by MRI (84.3% vs 15.7%, p < 0.001) and longer duration of disease (14.6 ± 7.8 vs 8.43 ± 5.9 months, p < 0.001). In a logistic regression model, the presence of lesions in spinal cord MRI (OR 3.5 [1.5-24.5]) and higher EDSS score (OR 1.7 [1.1-2.7]) were independently associated with pain. Conclusions: Pain is a frequent disabling symptom in MS and is associated with disability and spinal cord lesions.

INTRAMEDULLARY SJÖGREN SYNDROME

Sjogren syndrome (SS) is a systemic autoimmune disorder predominantly affecting the exocrine glands, involving the CNS in 20%–25% of cases. Previous neuropathologic specimens in Sjogren myelopathy have suggested a vasculitic pathophysiology. ### Case report. A 66-year-old woman developed sicca symptoms followed by subacutely evolving neck pain, paraparesis, and paresthesias below her neckline. She had 5 similar attacks over ensuing months, partially improved by IV methylprednisolone, but gradually became cane dependent and noted anesthesia below her chest. Her only regular medication was benazepril. One year later, her symptoms recurred, and she presented to our institution. On examination, there was flaccid hyporeflexic upper extremity paresis with areflexic paraplegia. A T5 sensory level was noted. There was no optic disc pallor, dysmetria, or dyssynergia. Brain MRI was unremarkable except for small vessel disease. Spinal MRI showed multiple patchily enhancing, longitudinal white matter lesions (several extending over 3 corresponding vertebral body segments) from the medullary spinal junction to the conus medullaris. CSF showed protein 208, glucose 79, 9 erythrocytes, and 9 leukocytes, including 6 lymphocytes, 2 histiocytes, and 1 neutrophil. CSF de novo immunoglobulin G (IgG) synthesis was 45.6 (−9.9 to 3.3 mg/day) and CSF IgG index was 0.8 (0.0–0.7). Possible matching IgG bands in serum and CSF were seen. SSA, SSB, antinuclear antibodies (1:320, normal 1:40), Smith (1:50), and RNP (1:100) were positive. Serum NMO …

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Identification of IgG subclasses' oligoclonal bands in multiple sclerosis CSF

IgG subclasses' oligoclonal bands in unconcentrated CSF from MS patients were detected by isoelectric focusing in agarose gel with subsequent immunoblotting using mouse monoclonal antibodies to human IgG subclasses and double-antibody avidin-biotin-alkaline phosphatase system. All MS CSF showed presence of oligoclonal bands specific to the IgG1 subclass; in addition, several of these samples also had oligoclonal bands specific to IgG3, IgG2, or IgG4, in order of decreasing frequency. Since the CSF of a greater number of MS patients showed oligoclonal bands specific to the IgG1 and IgG3 subclasses, the findings are consistent with those reported in patients with chronic viral infections and autoimmune diseases.

Acute peripheral facial palsy: CSF findings and etiology

CSF and serum were examined in acute and convalescence phase from 56 patients with acute idiopathic peripheral facial palsy. CSF protein analysis, viral and borrelia serology were performed. Borrelia infection was found in 9/56 cases and was often associated with inflammatory CSF findings. One patient each had serological evidence for a recent or ongoing infection with herpes simplex, varicella zoster, adeno, influenza B, echo and Epstein-Barr virus, but none had specific intrathecal antibody synthesis; 11 patients had a serological pattern compatible with a reactivated Epstein-Barr virus infection. Eleven patients displayed mononuclear CSF pleocytosis. Four of them had a borrelia infection. A disturbed blood-brain barrier was observed in 19 patients. Intrathecal immunoglobulin synthesis as indicated by elevated IgM-indices was found in 16 patients and by IgG indices in three. Nine patients had oligoclonal IgG bands in serum and CSF, three exclusively in CSF. It is concluded that patients with facial palsy often have inflammatory CSF findings, indicating a generalised central nervous system affection, and not only a mononeuritis. The importance of viral infections in the pathogenesis is still obscure. Borrelia is the most common infectious cause of facial palsy.

Diagnostic algorithm for the differentiation of leukodystrophies in early MS

Leukodystrophies are chronic progressive inherited white matter diseases frequently combined with an inborn error of metabolism. Some leukodystrophies clinically resemble chronic variants of multiple sclerosis (MS), while others exhibit multifocal MRI changes mimicking white matter changes known from MS imaging studies. The risk of misdiagnosing leukodystrophy as being MS is especially high in early disease stages comprising the possibility of initiating an inadequate therapy. Patients with clinical isolated syndromes should carefully be screened for positive family history, atypical clinical presentation or MRI pattern, symmetric involvement of long spinal tracts and peripheral nerves using evoked potentials and nerve conduction velocities and lack of oligoclonal bands in CSF all of which are "red flags" which consecutively may implicate consideration of leukodystrophy. Genetic or biochemical testing is widely available giving rise to a specific diagnosis in most patients.

Unusual findings in Leigh syndrome caused by T8993C mutation

The pathological nature of Leigh syndrome is highly variable and depends on the underlying mitochondrial or nuclear genome defect. Mitochondrial m.8993T>G and m.8993T>C mutations are responsible for both NARP (neurogenic weakness, ataxia and retinitis pigmentosa) and Leigh syndrome depending on the amount of mutant mtDNA. The clinical findings of Leigh syndrome caused by the m.8993T>C mutation are less severe than those associated with the m.8993T>G mutation, and ragged red fibers, oligoclonal bands in cerebrospinal fluid, and additional deficiencies of respiratory enzyme complexes are usually not found. This report presents a two year old girl with Leigh syndrome caused by a m.8993T>C mutation. Interestingly she had ragged red fibers in muscle tissue, oligoclonal bands in CSF and focal deficient histochemical staining for complexes I and IV.

Case of fulminant‐SSPE associated with measles genotype D7 from India: An autopsy study

Subacute sclerosing panencephalitis (SSPE), a post-measles progressive neurological disorder is still common in India because of indifferent vaccination compliance. However, the acute fulminant form of SSPE is extremely rare. An unusual case of fulminant SSPE in an 18-year-old man from south India with an ultra-short course of 19 days presenting with hemiparesis in absence of myoclonus and progressive cognitive decline, is reported. MRI showed frontal and parieto-occipital demyelination extending to nuclear areas. Antimeasles antibodies were demonstrable in CSF and serum with oligoclonal bands in CSF despite normal CSF protein and cell count. At autopsy, unlike classical SSPE, oligodendroglia containing measles viral antigen was sparse despite florid necrotizing leukoencephalitis with acute demyelination. Measles virus was isolated from the brain with hypermutation in M gene confirming the diagnosis. Phylogenetic analysis of the viral genotype indicated that it belonged to D7 genotype which is considered rare in India.

Bilateral visual loss and paraplegy in a patient with metastaic carcinoma of stomach

Abstract Purpose We present a case report of bilateral visual loss and paraplegy in patient with metastatic carcinoma of stomach. Methods 64‐year old male presented with painless visual loss on right eye, and one week later, he was blind on both eyes with no light perception and amaurotic pupils. One year earlier he was diagnosed with primary metastatic carcinoma of stomach and was treated by Xeloda and Docetaxel. Fundi revealed bilateral hyperemic disc oedema. Solu‐Medrol 1 g i.v. for three days had no effect. Results CT and MRI of brain showed no lesion that would explain his visual loss. Scotopic and photopic electroretinography was normal.Visual evoked potentials (VEP) on flash stimulation were nonrecordable. Specific onco‐neurologic antibodies in CSF and serum were negative:anti‐Ri(ANNA‐2),anti‐Yo,anti‐CV2(CRMP5),anti‐amphiphysin,anti‐Mal,anti‐Hu(ANNA‐1),anti‐Ma2(Ta‐). One month after onset of blindness, he had acute neurological deterioration with paresis of left leg and retention of urine which was diagnosed as Brown‐Sequard syndrome. MRI of spinal chord showed intramedular lesion between Th 6‐10. Oligoclonal bands in serum and CSF were identical, indicating systemic inflammation. Serum was sent for testing NMO‐IgG,but results are in process. Patient was restarted on high doses of Solu‐Medrol i.v. Slight improvement of vision was noted after few days of therapy, and flash‐evoked VEP was barely detectable. The discs were no longer swollen and appeared pale. Conclusion This unusual case of bilateral blindness due to optic neuropathy might be linked to atypical presentation of neuromyelitis optica or to paraneoplastic optic neuropathy caused by yet unknown antigen.

Multiple Sclerosis

Multiple Sclerosis (MS) is the most common demyelinating disease affecting the central nervous system of young adults living in western countries. The clinical suspicion of demyelination, as a pathological process, is high when a young adult develops one or more neurological episodes indicating a damage to white matter tracts within the central nervous system, especially when the optic nerve, brainstem, or spinal cord is involved. The patient with episodes disseminating in time, each of which can be attributed to demyelination, requires no investigation prior to establishing the diagnosis of clinically definite MS, if the age of clinical presentation falls between 20 and 50 years, if different anatomical sites within the central nervous system have necessarily been affected on separate occasions, and if the clinical manifestation is typical for MS. MS in Asian populations is characterized by selective and dominant involvement of the optic nerve and spinal cords, as well as some incidence of brainstem lesion and symptoms. About 35~40% of cases of MS in Korea are of this optico-spinal type. Optico-spinal MS (OSMS) generally has a higher female-to-male ratio than conventional MS. OSMS is also characterized by frequent relapses, severe disability, few brain lesions on MRI, and a very lower incidence of oligoclonal bands in CSF. Neuromyelitis Optica (NMO) (Devic syndrome), which causes severe optic neuritis (ON) and longitudinally extensive transverse myelits either with a monophase or relapse-remitting pattern, is rare in Korean. NMO-IgG was reported to be helpful for the diagnosis of early-stage NMO and differential diagnoses of MS.

Recombinant immunoblot for assessment of intrathecally synthesised paraneoplastic antineuronal antibodies in cerebrospinal fluid from patients with paraneoplastic neurological syndromes

Background: Beside of pathophysiological interest, estimation of intrathecal synthesis (IS) of paraneoplastic antineuronal antibodies may increase the diagnostic sensitivity in rare cases of patients with clinically suggestive paraneoplastic neurological syndromes (PNS) and negative or uncertain results in serum. Detection of antigen-specific oligoclonal bands (OCB) in CSF seems to be the most sensitive marker of IS. However, this technique is not suitable for routine laboratory testing.

Inflammatory/demyelinating central nervous system involvement in familial Mediterranean fever (FMF): coincidence or association?

Familial Mediterranean fever (FMF) is an inherited inflammatory disease characterized by recurrent febrile polyserositis. Central nervous system (CNS) involvement in FMF is uncommon, but recently cases with multiple sclerosis (MS) and FMF have been reported. Here we assess patients with both FMF and MS, in order to clarify any relationship between FMF and MS, and to evaluate disease characteristics. Our MS database between 1986-2005 was screened retrospectively, and patients with both FMF and inflammatory/demyelinating CNS disease were evaluated among a total of 2800 patients including definite MS (n = 2268) and other demyelinating disorders. There were 12 patients with FMF, who developed a CNS disorder with multifocal white matter lesions. Median age at onset of FMF was 7 years, and median age at neurological onset was 26.8 years. Nine patients (including two siblings) had definite MS according to clinical and MRI findings, whereas 3 patients had atypical features suggesting other demyelinating disorders. Disease severity varied among the patients between very mild to a fatal course. All 8 patients evaluated for oligoclonal IgG bands in CSF were positive. The rate of FMF among our patients with definite MS is almost 4 times the expected prevalence in Turkey. Our series including a sibling pair concordant for FMF and MS may suggest that similar genetic susceptibility and environmental factors might be responsible, although coincidence still remains a possibility. A prospective study on a larger sample seems to be justified.

White matter lesions in a young HIV–positive immunocompetent patient without cerebrovascular risc factors due to an ICA–thrombus

Sirs: White matter lesions in HIVpositive patients may have various causes. Besides inflammatory and neoplastic diseases [1], vascular processes should be considered. Hemostasis disturbances and thrombotic microangiopathy have been described in HIV-infected patients [5, 6, 8] and venous or arterial thrombosis have been observed in HIV-infected patients [3, 10]. To the best of our knowledge, internal carotid artery (ICA) thrombosis has not yet been described in HIVpositive patients in the absence of other major thrombophilic factors. A 36-year old HIV positive man presented with a 3-week history of slowly progressive mild paresis of the left upper limb. Two days before presentation, he complained of a facial numbness on the left side and one day later a drooping corner of the mouth on the left. HIVinfection had been diagnosed 4 years previously. At presentation, CD4+ cells were 1,220/ml and HIV stage was CDC A1. The patient was on no medication and had never received antiretroviral treatment. On neurological examination, the patient had a left-sided supranuclear facial palsy in combination with slight paresis (4+/5), hypesthesia and hypalgesia of the upper left limb. There were no other abnormal neurological findings. MRI of the brain revealed multifocal lesions in the right hemisphere, suggestive of cerebral vasculitis (Fig. 1A). Lumbar puncture on the day after admission showed CSF with a mild pleocytosis with 98/3 cells (88 % lymphocytes), 40.8 mg/dl total protein and identical oligoclonal bands in CSF and serum. Serological tests for lues, borreliosis, and toxoplasmosis in serum, as well as for HSV1/2, CMV, EBV, and Enterovirus in serum and liquor were normal. Neither these viruses nor JCV could be detected in CSF by PCR. Fungal culture was negative. HIV load in plasma was 75 cop/ml, in CSF 253 cop/ml. Titers of further auto-antibodies (ANA, Anti-Phospholipid-Ab, antids-DNA-Ab) were within normal limits. Electrolytes, full blood count, lipids, inflammatory markers, and coagulation markers (PTT, TPZ-INR, APCRes, PrC, PrS, LupInh, Fbg, D-Dimer, factor VIII) were in the normal range. Toxicological screening gave no pathological findings. Neurosonological examination revealed a 50 % stenosis of the right internal carotid artery over a 4.5 cm distance immediately above the carotid bifurcation due to an irregularly configured, hypoechoic and partially fluctuating intraluminal mass. Thus, an intraluminal thrombus was suspected and was confirmed by computed tomographic angiography (CTA) (Fig. 1B, C). No hint of cardioembolic predisposition was seen in transesophageal echocardiography. No abnormality was detected by ultrasonography of the venous system of the legs and radiography of the chest. Clinical symptoms and white matter lesions could be explained by recurring thromboembolic events and thromboendarterectomy was initiated. Following surgery, treatment with clopidogrel 75 mg daily was started; 2.5 months later, the patient reported a continuous improvement of his complaints and cerebral CT confirmed that no ischemic events had occurred in the meantime. In contrast to most of the possible causes [1], the unilateral occurrence in our patient suggested an ipsilateral vascular disease as the likely cause of the lesions, whereas pleocytosis in the CSF prompted us to search for infectious or vasculitic origin. However, as demonstrated with our case, mild pleocytosis is a common finding in HIV-positive patients and should not limit the diagnostic approach [2]. Thrombosis of the internal carotid artery already has been reported in young patients with prothrombogenic factors [11], following cervical trauma and dissection of the carotid artery [9], but has sometimes remained unexplained [4]. Thrombotic microangiopathy is a well known complication in the advanced phases of HIV-infection and in association with specific conditions [8] and thrombosis has been observed in HIV-infected patients [3, 5, 10, 12]. However, against that argument, our patient had no obvious triggering cause and a normal CD4+ count. Some authors have hypothesized that proteinase-inhibitors may promote the thombogenesis [7, 13]. As the patient was on no medication, this argument would not apply in our case. Furthermore, there was no history of preceding cervical or head trauma. Further molecular genetic examination revealed heterozygosity for the PAI-1, XII and the MTHFR gene. Despite these hereditary prothrombotic components, the speLETTER TO THE EDITORS

Correlation between the IgG index, oligoclonal bands in CSF, and the diagnosis of demyelinating diseases

Intrathecal immunoglobulin synthesis can be assessed by different approaches. It can be measured quantitatively by the IgG index or qualitatively by isoelectric focusing (IEF) to detect oligoclonal bands (OCB). In this study we investigated if there is a correlation between the frequency of OCB and the IgG index and if the IgG index predicts the diagnosis of a demyelinating CNS disease (DMD). We found a positive correlation between the IgG index and the frequency of OCB as well as the probability of DMD. We conclude that quantitative assessment of CSF-IgG can be useful because it is easier and quicker to perform than IEF but cannot replace IEF in general because this is the most sensitive method to detect abnormal IgG in CSF.