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To date, it remains largely unknown whether there is in radiologically isolated syndrome (RIS) brain damage beyond visible T2 white matter lesions. We used single- voxel proton magnetic resonance spectroscopy and diffusion tensor imaging (3 T MRI) to analyze normal-appearing brain tissue regions in 18 RIS patients and 18 matched healthy controls. T2-hyperintense lesion volumes and structural brain volumes were also measured. The absolute metabolite concentrations and ratios of total N-acetylaspartate+N-acetylaspartyl glutamate (NAA), choline-containing compounds, myoinositol, and glutamine-glutamate complex to creatine were calculated. Spectral analysis was performed by LCModel. Voxelwise morphometry analysis was performed to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Compared with healthy controls, RIS patients did not show any significant differences in either the absolute concentration of NAA or NAA/Cr ratio in mid-parietal gray matter. A trend toward lower NAA concentrations (-3.35%) was observed among RIS patients with high risk for conversion to multiple sclerosis. No differences in the other metabolites or their ratios were observed. RIS patients showed lower fractional anisotropy only in clusters overlapping lesional areas, namely in the cingulate gyrus bilaterally and the frontal lobe subgyral bilaterally (P < 0.001). Normalized brain and cortical volumes were significantly lower in RIS patients than in controls (P = 0.01 and P = 0.03, respectively). Our results suggest that in RIS, global brain and cortical atrophy are not primarily driven by significant occult microstructural normal appearing brain damage. Longitudinal MRI studies are needed to better understand the pathological processes underlying this novel entity., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: To estimate the seroprevalence of anti-JCV antibodies, seroconverting rates and evolution of antibody levels in a multiple sclerosis (MS) Spanish cohort., Methods: Multicenter, retrospective cross-sectional and longitudinal study. The JCV seroprevalence was analyzed in 711 MS patients by using 1st (STRATIFY-1) and 2nd generation (STRATIFY-2) two-step ELISA over 2.65 (±0.97) years. Seroconversion rate was obtained over 2 samples from 314 patients, and index stability from 301 patients with 3 or more samples available. The effect of each ELISA generation, demographics, clinical characteristics and therapy on seroprevalence was assessed by logistic regression., Results: The overall anti-JCV seroprevalence was 55.3% (51.6-58.9), similar across regions (p=0.073). It increased with age (p<0.000) and when STRATIFY-2 was used (60.5%, p=0.001). Neither sex nor immunosuppressive therapy had any influence. Yearly seroconversion rate was 7% (considering only STRATIFY-2). Serological changes were observed in 24/301 patients, 5.7% initially seropositive reverted to seronegative and 7% initially seronegative changed to seropositive and again to seronegative, all these cases had initial index values around the assay's cut-off., Conclusions: JCV seroprevalence in Spanish MS patients was similar to that reported in other European populations. Changes in serostatus are not infrequent and should be considered in clinical decisions., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To (1) determine the value of the recently proposed criteria of neuromyelitis optica (NMO) spectrum disorder (NMOSD) that unify patients with NMO and those with limited forms (NMO/LF) with aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies; and (2) investigate the clinical significance of the serologic status in patients with NMO., Methods: This was a retrospective, multicenter study of 181 patients fulfilling the 2006 NMO criteria (n = 127) or NMO/LF criteria with AQP4-IgG (n = 54). AQP4-IgG and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) antibodies were tested using cell-based assays., Results: Patients were mainly white (86%) and female (ratio 6.5:1) with median age at onset 39 years (range 10-77). Compared to patients with NMO and AQP4-IgG (n = 94), those with NMO/LF presented more often with longitudinally extensive transverse myelitis (LETM) (p < 0.001), and had lower relapse rates (p = 0.015), but similar disability outcomes. Nonwhite ethnicity and optic neuritis presentation doubled the risk for developing NMO compared with white race (p = 0.008) or LETM presentation (p = 0.008). Nonwhite race (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.4-13.6) and older age at onset were associated with worse outcome (for every 10-year increase, HR 1.7, 95% CI 1.3-2.2). Patients with NMO and MOG-IgG (n = 9) had lower female:male ratio (0.8:1) and better disability outcome than AQP4-IgG-seropositive or double-seronegative patients (p < 0.001)., Conclusions: In patients with AQP4-IgG, the similar outcomes regardless of the clinical phenotype support the unified term NMOSD; nonwhite ethnicity and older age at onset are associated with worse outcome. Double-seronegative and AQP4-IgG-seropositive NMO have a similar clinical outcome. The better prognosis of patients with MOG-IgG and NMO suggests that phenotypic and serologic classification is useful.

The unanticipated magnetic resonance imaging (MRI) detection in the brain of asymptomatic subjects of white matter lesions suggestive of multiple sclerosis has recently been named as radiologically isolated syndrome (RIS). The pathophysiological processes of RIS remain largely unknown and questions as to whether gray matter alterations actually occur in this entity are yet to be investigated in more detail. By means of a 3 T multimodal MRI approach, we searched for cortical and deep gray matter changes in a cohort of RIS patients. Seventeen RIS patients, 17 clinically isolated syndrome (CIS) patients (median disease duration from symptom onset = 12 months), and 17 healthy controls underwent MRI and neuropsychological testing. Normalized deep gray matter volumes and regional cortical thickness were assessed using FreeSurfer. SIENAX was used to obtain normalized global and cortical brain volumes. Voxelwise morphometry analysis was performed by using SPM8 software to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Although no differences were observed between CIS and healthy controls groups, RIS patients showed significantly lower normalized cortical volume (673 ± 27.07 vs 641 ± 35.88 [cm³ × 10³, Tukey P test = 0.009) and mean thalamic volume (0.0051 ± 0.4 vs 0.0046 ± 0.4 mm, P = 0.014) compared with healthy controls. RIS patients also showed significant thinning in a number of cortical areas, that were primarily distributed in frontal and temporal lobes (P < 0.05, uncorrected). Strong correlations were observed between T2-white matter lesion volume and regional cortical thickness (rho spearman ranging from 0.60 to 0.80). Our data suggest that white matter lesions on T2-weighted images are not the only hallmark of RIS. Future longitudinal studies with larger samples are warranted to better clarify the effect of RIS-related white matter lesions on gray matter tissue., Competing Interests: The authors have no funding and conflicts of interest.

Unlabelled: Up until now, no information has existed regarding a comparison of the pattern and frequency of cognitive deficits between radiologically isolated syndrome (RIS) and clinically isolated syndrome (CIS) patients. Within this objective, Rao's Brief Repeatable Battery and Stroop test were administered to 28 RIS patients, 25 CIS patients, and 22 healthy controls., Conclusions: The prevalence of cognitive deficits in RIS was similar to that of CIS. Cognitive deficits seem to be present in RIS patients regardless of the presence of risk factors for a future symptomatic demyelinating event., (© The Author(s), 2015.)

Background: Radiologically isolated syndrome (RIS) is characterized by incidental lesions suggestive of multiple sclerosis (MS) on MRI without typical symptoms of MS. Clinically isolated syndrome (CIS) is characterized by a first episode of neurologic symptoms caused by demyelination in the central nervous system. To date, psychiatric disorders have not been systematically addressed in RIS subjects. We assessed emotional disturbances, personality features and health-related quality of life (HRQoL) in a cohort of RIS patients as compared with clinically isolated syndrome (CIS)., Methods: Twenty-eight RIS patients, 25 clinically isolated syndrome (CIS) patients, and 22 healthy subjects were enrolled in the study. Participants were administered a mood scale (Hamilton Depression Rating Scale), behavioural measures (Personality Assessment Inventory), and fatigue measures (Fatigue Impact Scale for Daily Use). HRQoL was quantified using the EuroQol-5., Results: 14 (50%) of RIS patients had clinically significant depression, with over one-third of these having moderate depression, scores virtually identical to those observed in CIS patients. 11 of 28 (39.3%) subjects with RIS had anxious depression, a figure three times higher than that found in CIS patients. RIS patients' HAMD-17 total score showed a very strong correlation with severity of fatigue. In addition, RIS patients reported lower HRQoL (p = 0.036) and a significantly higher symptoms load for somatisation compared to both CIS and control groups (p < 0.002)., Conclusion: RIS patients had high rates of depression, particularly anxious depression and somatization. Future studies are warranted to clarify whether these psychiatric disturbances are causally associated with a distinct white matter psychopathologic process., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Diffuse superficial siderosis of the central nervous system (CNS) is a rare condition due to hemosiderin deposits in the subpial layers of the brain and spinal cord. The source of chronic or recurrent bleeding into the subarachnoid space is detected in only 50 % of cases. The most characteristic symptoms are cerebellar ataxia and sensorineural hearing impairment. T2-weighted gradient echo magnetic resonance imaging constitutes the diagnostic method of choice., Case Reports: We report four patients of diffuse superficial siderosis of the CNS associated to cerebral amyloid angiopathy, oral anticoagulation, schwannoma VIII, and without known source of bleeding in one case. Two patients developed cerebellar ataxia, three of them present transient focal neurological episodes, one dementia and, the last one, the diffuse superficial siderosis of the CNS is a radiological finding. No clinical progression was observed during follow-up (2-11 years) in three of them. The patient with cerebral amyloid angiopathy progresses to dementia., Conclusions: Transient focal neurological episodes were the most common symptom in our cases of diffuse superficial siderosis of the CNS. The natural history of this condition is not very known and may be regarded as a radiological finding.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic arteriopathy related to Notch3 mutations, is difficult to diagnosis. The goal of this study was to determine the value of clinical, immunohistochemical, and molecular techniques for the diagnosis of CADASIL. Clinical features and the immunohistochemical and molecular findings in 200 subjects with suspected CADASIL in whom 93 biopsies and 190 molecular studies are reported. Eighteen pathogenic mutations of the Notch3 gene, six of them previously unreported, were detected in 67 patients. The clinical features did not permit differentiation between CADASIL and CADASIL-like syndromes. The sensitivity and specificity of the skin biopsies was 97.7% and 56.5%, respectively, but increased to 100% and 81.5%, respectively, in cases with proven family history. In conclusion, a clinical diagnosis of CADASIL is difficult to determine and confirmatory techniques should be used judiciously.

Introduction: Chronic lymphatic leukaemia (CLL) is the most frequent form of leukaemia in the adult population in western countries. Only 7.2% of the complications of CLL are neurological and most of them are secondary to an infection by herpes zoster virus., Case Report: We report the case of a 71-year-old female with B-type CLL in stage IV or type C that was progressing and becoming diffuse large B-cell lymphoma (Richter's syndrome), who developed an incomplete axonotmesis of the left peroneal nerve and numerous violet-coloured nodules under the skin in the left knee. Magnetic resonance imaging showed signs of diffuse infiltration into the subcutaneous tissue and the muscles of the left leg; a biopsy study of one of the subcutaneous nodules revealed a lymphoid infiltration by large B-cells. In this patient, the injury to the left peroneal nerve was probably secondary to a lymphoid infiltration of the nerve from adjacent infiltrated soft tissues., Conclusion: Peripheral neuropathy due to direct infiltration can be a neurological complication of CLL that has not be reported to date, but which is known to occur in other lymphoproliferative processes.

Introduction: Delays in the treatment of a stroke constitute a factor that leads to a more unfavourable prognosis. Shortening the delay time in the health care of these patients is essential in order to reduce the morbidity and mortality rates of this disease., Aims: Our aim was to analyse the causes that bring about delays in getting stroke patients to hospital., Patients and Methods: A prospective analysis was conducted of 133 patients who visited the Emergency Department. A survey carried out during the first 48 hours collected information on the clinical characteristics and the steps followed by the patient before arriving at the hospital. We considered the time that elapsed to be adequate if patients arrived at the hospital in less than 2 hours. A univariate and multivariate analysis was performed to evaluate the factors that could extend this time., Results: The mean time elapsed before the patient reached hospital was 502 minutes (interval: 11-5,700). A total of 42.5% arrived in less than 2 hours and 58.2% got there in less than 3 hours. The univariate analysis showed that females, those with a low cultural level, the most severe cases, those who went straight to hospital and those who used the emergency services all arrived more quickly. In the multivariate analysis only the more severe cases and those who went straight to hospital ran less risk of a delayed arrival., Conclusions: The time stroke patients take to reach hospital varies greatly. The main factors that influence the time that elapses before arrival are the severity of the symptoms and going straight to hospital.

Introduction: Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system with an unknown origin, although the immunological system plays a crucial role in its pathogenesis. It has been observed that the relatives of MS patients very often have other autoimmune diseases (ADs) and it has been suggested that there may be susceptibility genes that are common to this group of diseases., Aims: Our aim was to estimate the prevalence of ADs in first and second degree relatives of patients with MS and to determine the coexistence of other ADs in MS patients., Patients and Methods: We selected 251 patients with MS defined by the Poser criteria and face-to-face interviews with the patients and/or their relatives were conducted to investigate the following ADs: MS, rheumatoid arthritis, systemic lupus erythematosus, polyarteritis nodosa, autoimmune thyroid disease (ATD), inflammatory bowel disease, myasthenia gravis, type I diabetes mellitus (DMI) and psoriasis. RESULTS. 29.9% of the patients with MS had a first and/or second degree relative with an AD. Prevalence of ADs in first degree relatives was 15.5%, 30% in familial MS and 40% if the patient had both MS and another AD. The most frequent ADs were: MS 27%, psoriasis 18%, ATD 16% and DMI 15%. 15 patients had MS and another AD: six ATD, three DMI, four psoriasis, one inflammatory bowel disease and one myasthenia gravis., Conclusions: These findings lend support to the existence of susceptibility genes that are common to the different ADs and would act as risk factors.

Objectives: To determine the prevalence and incidence of multiple sclerosis (MS) in the city of Las Palmas (Canary Islands, Spain), geographically belonging to north-western Africa, but with European ancestry., Methods: This population-based survey was conducted for a period of 5 years (1998-2002) in a Sanitary District of Las Palmas city (28 degrees 20' N), with a population of 82,623 inhabitants. Multiple sources were periodically investigated for case ascertainment. Patients with definite and probable MS were included., Results: Sixty-four patients with MS were identified on prevalence day, December 31, 2002. According to Poser's criteria the crude prevalence rate was 77.5 per 100,000 (95% CI: 59.7-98.9). This rate decreased to 73.8 (95% CI: 56.5-94.8) according to McDonald's criteria. Age-adjusted rates for the world and European standard populations were 61.6 (95% CI: 47.1-78.9) and 70.6 (95% CI: 55-89), respectively. Prevalence was higher for women aged 25-44 years. In 17 patients onset of MS occurred within the study period. Average annual incidence was 4.1 per 100,000 (95% CI: 2.4-6.6)., Conclusions: The prevalence and incidence rates in Las Palmas city are close to those reported from Continental Spain and other countries of southern Europe with similar social and ethnic background. These results highlight the role of racial-ethnic factors in the genesis of MS.

Introduction: Multiple sclerosis (MS) is an autoimmune disease that occurs in genetically predisposed individuals. Its inheritance is polygenic. Genetic epidemiology studies have shown an increased familial aggregation. AIM. To determine the prevalence of familial MS (fMS) in a series of patients from the Canary Islands., Patients and Methods: From a cohort of 266 patients with defined MS, during a 6-year period, we investigated prospectively by personal interviews the presence of MS on first and second degree relatives. We analysed as well the presence of HLA DRB1 in affected families, and also clinical and demographic characteristics in fMS and compared them with sporadic MS (sMS)., Results: fMS prevalence was 13.9% (27 non-related families with 50 affected individuals). The HLA DRB01*1501 allele were present in 51,8% of familial cases. We could not found either intrafamilial concordance in clinically affected regions and age of onset or clinical evolution. We have not found any phenotypic differences between familial and sMS., Conclusions: The prevalence of fMS in our series is comparable to that in other Mediterranean populations. Our results do not support that fMS was a different clinical entity of sMS and intrafamilial concordance in its clinical expression.

Hypercoagulable states are frequently associated to malignancies. We report the case of a 67 year-old patient with prostatic cancer (T3NxM1) and deep venous thrombosis, whose initial coagulation studies were normal. He was treated with acenocumarol and hormonal blockade with flutamide and leuprolerin acetate. Six months later he developed recurrent brain ischemic strokes in the territories of both median cerebral arteries, that did not respond to anticoagulant treatment. Coagulation studies, showed a procoagulant activity with a probable paraneoplastic origin. We conclude that prostatic adenocarcinoma treated with hormonal blockage may promote a complex procoagulant state leading to recurrent occlusive arterial disease, refractory to anticoagulation.

Objective: To assess the performance of a polymerase chain reaction (PCR) method in cerebrospinal fluid (CSF) for the diagnosis of nervous system infections caused by herpesvirus, and to estimate the incidence of encephalitis due to herpes simplex virus type 1 in the adult population of the island of Gran Canaria., Methods: We studied 330 CSF specimens from 312 patients (281 HIV-negative and 31 HIV-positive) remitted to investigate clinically suspected encephalitis or meningitis, or to study neuropathy or demyelinating disease. A multiplex PCR technique was used to detect herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), human cytomegalovirus (CMV), Epstein-Barr virus and human herpesvirus type 6. The patients' clinical records were reviewed to establish the definite diagnosis., Results: Nine samples from eight patients (2.6%) showed positive results (9.7% of patients with pathological CSF and none with normal CSF). The eight patients had clinical and analytic findings of herpesvirus nervous system infection: HSV-1 DNA in four patients with encephalitis, HSV-2 DNA in one patient with meningitis, VZV DNA in two patients with meningitis and CMV DNA in one HIV-positive patient with encephalitis. Herpesvirus was the cause of 50% of encephalitis cases and 10% of meningitis cases. The incidence of HSV-1 encephalitis was five cases per million inhabitants per year., Conclusions: Diagnosis of herpesvirus nervous system infections by PCR in CSF is not appropriate when CSF parameters are normal. We found a higher incidence of herpesvirus encephalitis than has been reported in other studies.

Introduction: Increased intracranial pressure (ICP) due to complete middle cerebral artery territory infarction does not respond to medical treatment and is often followed by transtentorial herniation and death. Some authors have reported good outcome after performing decompressive hemicraniectomy in this condition. The potential clinical benefit of intracranial pressure reduction by means of an external ventriculostomy in such cases is unknown., Case Report: The present paper discusses the case of a 33 year old female who suffered a massive infarction of the territory of the right middle cerebral artery with transtentorial herniation and left lateral ventricular dilation who rapidly improved after performing external ventriculostomy without hemicraniectomy. The brain tissue partial oxygen pressure (PtiO2) was monitored in the left frontal lobe and a fair correlation with clinical events was found., Conclusions: External ventricular drainage without hemicraniectomy could be lifesaving in some case of massive ( malignant ) hemispheric infarction and more studies on this therapeutic approach would be needed. Monitoring PtiO2 in these patients would be useful in adopting therapeutic decisions.

Introduction: The prevalence of epilepsy in multiple sclerosis (MS) is low and the occurrence of an epileptic seizure as a first sign of this illness is even more infrequent. The relationship between both these illnesses is not clear; as epilepsy is a common condition, a coincidental association only could exist between the two diseases., Objective: To establish a nexus of causality between epilepsy an MS. Clinical case. We present one case of epileptic seizures as the first manifestation of MS. The patient was a woman of 25 years old. The only result of the clinical examination was a right homonymous inferior cuadrantanopsy. The patient presented a high Tibbling index, lesions of demyelination in the subcortical occipital region and semioval centrum in the MRI and a pathological electroencephalogram; also, the visual and auditory evoked potential latency were delayed., Conclusions: We related he results of the neuroimaging, the clinical examination and the complementary tests of the patient. The appears to be a causal association between epilepsy and MS.

Background and Methods: Human infections caused by Listeria monocytogenes often present as sporadic cases without any epidemiological relationship among them; however they also appear as outbreaks that are usually detected by an increase in the number of cases diagnosed by hospitals of the geographic area. Between December 1991 and May 1993, twenty four cases of listeriosis were detected in three hospitals of Las Palmas de Gran Canaria; and they were classified as an outbreak. Our report describes its clinical, epidemiological and microbiological aspects., Results and Conclusions: Twenty four cases of listeriosis were diagnosed, 12 occurred in pregnant women or neonates (5 and 7 respectively) and 12 in non pregnant adults. All adult infections were community-acquired. The incidence rate was, for the epidemic area, 76.3 cases per million population during the period considered (18 months). Among non pregnant adults, 9/12 patients had some underlying disease and 9/12 presented CNS affection (meningitis and/or cerebritis). In the group of pregnant women, 4 cases occurred in the second trimester and fetal loss was caused; one case was detected in the third trimester and four weeks later the patient delivered an unaffected infant. All cases of neonatal listeriosis presented as early-onset sepsis. Of the 24 strains of L. monocytogenes, 21 were serotype 4, two were serotype 1 and one was not typeable. Strains from 12 patients were available for epidemiological analysis, seven of which corresponded to the same pattern and there were three more different patterns.

Diastematomelia presenting in adult life has long been considered a rare occurrence. With the development of modern imagining techniques, cases of adult are being discovered with increasing frequency, but their exact number remains unclear. It occurs most often in the lumbar region, is rarely located above the level of T3 and it present clinical features such as deformity of the food, peculiar posture, or gait disturbance. The symptoms and signs of diastematomelia usually are recognized in children. We are reporting the case of an adult patient who had a forme frustre of Sjögren's syndrome and thoracic diastematomelia presenting as a acute myelopathy. Although in most of patients, the pathogenesis of the neurological deficits could be attributed to lesions such as spondylosis, herniation of a disc, traction injury or the tethering effect derived from an osseous septum or a fibrous band, in our patients was absent. We suggested as contributory cause to damage of the spinal cord a vascular ischemic mechanism during flexion and extension of the spine, and we postulated the role that anti-Ro (SS-A) antibodies play in the immunopathogenesis (mediating or potentiating) vascular injury by altering vascular endothelial function or proliferation.

The appearance of chorea due to systemic lupus erythematosus is extremely rare. A greater frequency of circulating anticoagulant, false positive luetic serology and antiphospholipid antibodies has been recently detected in these patients. For this reason, it has been postulated that these could be involved in the genesis of the chorea through a thrombotic mechanism or autoimmune encephalitis. We describe a case or chorea in a female patient with systemic lupus erythematosus.

Both ex-vacuo and non-reabsorptive hydrocephalus can present with a similar clinical triad of dementia, gait disturbances and incontinence. From a prognostic point of view, however, a great difference exists due to the possibility of surgical treatment with cerebrospinal fluid shunting in non-reabsorptive hydrocephalus. The difficulty lies in a correct preoperative diagnosis. In this study 37 patients aged from 60 to 72 with a clinical history suggestive of non-reabsorptive communicating hydrocephalus were evaluated; the diagnostic tests applied to them were: computerized axial tomography, infusion test with Nelson's technique and intracranial pressure monitoring. A clear correlation was observed between the clinical improvement obtained after a cerebrospinal fluid shunt had been placed and the presence of pathological computerized axial tomography (hydrocephalus without increased sulci with or without trans-ependymal edema) or the pathological infusion test (intracranial pressure increase over 2 mm Hg/min and no decrease back to the basal level once the infusion had ended). No correlation was observed between the different recordings obtained from the intracranial pressure monitoring and the surgical results. The clinical data which most easily revert are the gait disturbance, dementia and incontinence in this order and, more so, in patients with known etiology. Since non-reabsorptive hydrocephalus and ex-vacuo hydrocephalus may co-exist, mostly in elderly patients, it is important to further develop the dynamic studies of intracranial pressure with the aim of offering a more reliable surgical prognosis.