Human herpesvirus 6 infection as a trigger of multiple sclerosis: an update of recent literature.

BACKGROUND: This is an update on the existing evidence regarding a relationship between infection with human herpesvirus 6 (HHV-6) and multiple sclerosis (MS) in order to contribute on the attempt to define the nature and strength of that relationship. RESULTS: Study quality was assessed using the criteria proposed by Moore and Wolfson and by the classification criteria used by the Canadian Task Force on the Periodic Health Examination. Studies were categorized both by experimental technique and by quality (high [A], intermediate [B], and low [C]) as determined by the Moore and Wolfson criteria. Overall, 27 (90%) of 30 studies, 18 (86%) of which were classified as A quality, reached a statistically significant result. According to the Canadian Task Force classification, all studies were categorized as evidence of qualityII-1. Limitations of the available experimental techniques and perspectives for future research are discussed. CONCLUSIONS: The current review continues to emphasize the need for further, objective, evidence-based examination of the relationship between HHV-6 infection and multiple sclerosis.

Atrophy of optic nerve detected by transorbital sonography in patients with demyelinating diseases of the central nervous system.

BACKGROUND AND PURPOSE: Transorbital sonography (TOS) has emerged as promising imaging method for the diagnosis and follow-up of acute optic neuritis (ON). Available studies report an increase in the optic nerve diameter (OND) and the optic nerve sheath diameter (ONSD) in the case of a first episode of ON in the affected eye compared to either the contralateral unaffected eye or controls. However, the utility of TOS in the case of recurrent episodes of ON has never been assessed. METHODS: In our prospective cohort study, the diagnostic utility of TOS in patients with demyelinating diseases of the central nervous system was assessed, and the association between TOS, optical coherence tomography (OCT) and visual evoked potentials was examined further. RESULTS: Seventy-eight patients with a history of demyelinating disorders of the central nervous system (mean age 38.2 ± 14.2 years; 24% with acute ON) were included. No differences in the OND (3.2 ± 0.5 mm vs. 3.2 ± 0.4 mm) and ONSD (5.1 ± 0.8 mm vs. 5.1 ± 0.7 mm) measurements were found between patients with and without acute ON. Papillary swelling was more frequent in patients with acute ON (14.2% vs. 1.5%, P = 0.002). Patients with a history of previous ON were found to have lower OND (P < 0.001) and ONSD (P = 0.007) compared to patients without a history of previous ON. TOS measurements were inversely associated with disease duration and positively correlated with OCT findings. No association with visual evoked potential measurements was found. CONCLUSION: No evidence was found for TOS-sensitive differences in the OND and ONSD of patients with demyelinating diseases, according to the presence of acute ON. The association between TOS and OCT measurements deserves further investigation.

Safety of urgent endarterectomy in acute non-disabling stroke patients with symptomatic carotid artery stenosis: an international multicenter study.

BACKGROUND AND PURPOSE: International recommendations advocate that carotid endarterectomy (CEA) should be performed within 2 weeks from the index event in symptomatic carotid artery stenosis (sCAS) patients. However, there are controversial data regarding the safety of CEA performed during the first 2 days of ictus. The aim of this international, multicenter study was to prospectively evaluate the safety of urgent (0-2 days) in comparison to early (3-14 days) CEA in patients with sCAS. METHODS: Consecutive patients with non-disabling (modified Rankin Scale scores ≤2) acute ischaemic stroke or transient ischaemic attack due to sCAS (≥70%) underwent urgent or early CEA at five tertiary-care stroke centers during a 6-year period. The primary outcome events included stroke, myocardial infarction or death during the 30-day follow-up period. RESULTS: A total of 311 patients with sCAS underwent urgent (n = 63) or early (n = 248) CEA. The two groups did not differ in baseline characteristics with the exception of crescendo transient ischaemic attacks (21% in urgent vs. 7% in early CEA; P = 0.001). The 30-day rates of stroke did not differ (P = 0.333) between patients with urgent (7.9%; 95% confidence interval 3.1%-17.7%) and early (4.4%; 95% confidence interval 2.4%-7.9%) CEA. The mortality and myocardial infarction rates were similar between the two groups. The median length of hospitalization was shorter in urgent CEA [6 days (interquartile range 4-6) vs. 10 days (interquartile range 7-14); P < 0.001]. CONCLUSIONS: Our findings highlight that urgent CEA performed within 2 days from the index event is related to a non-significant increase in the risk of peri-procedural stroke. The safety of urgent CEA requires further evaluation in larger datasets.

The diagnostic yield of transesophageal echocardiography in patients with cryptogenic cerebral ischaemia: a meta-analysis.

BACKGROUND AND PURPOSE: The diagnostic utility of transesophageal echocardiography (TEE) in patients with cryptogenic ischaemic stroke (IS) or transient ischaemic attack (TIA) remains controversial. METHODS: A systematic review and meta-analysis was performed according to PRISMA guidelines to estimate the pooled prevalence of potential cardioembolic causes detected by TEE in prospective observational studies of cryptogenic IS/TIA. Cardiac conditions causally associated with cerebral ischaemia were considered to be intramural thrombi and intracardiac tumors according to ASCO phenotyping of IS. RESULTS: Thirty-five eligible studies, comprising 5772 patients (mean age 53.6 years, 56.9% men) were identified. The most common TEE finding was ascending aorta and/or aortic arch atheroma [51.2% (27.4%-74.5%)], followed by patent foramen ovale (PFO) [43.2% (36.3%-50.4%)]. Complex aortic plaques and large PFOs were reported in 14% (10.2%-18.9%) and 19.5% (16.6%-22.8%) of TEE evaluations. The prevalence of atrial septal aneurysm was 12.3% (7.9%-18.7%) and was significantly higher in conjunction with PFO presence (risk ratio 2.04, 95% confidence interval 1.63-2.54, P < 0.001). The prevalence of left atrial thrombus [3.0% (1.1%-8.3%)] and spontaneous echo contrast [3.8% (2.3%-6.2%)] was low. The prevalence of intracardiac tumors was extremely uncommon [0.2% (0%-0.7%)]. Significant heterogeneity was identified (I(2) > 60%) in the majority of analyses. Heterogeneity was not affected by cryptogenic stroke definition (TOAST versus alternative criteria). After dichotomizing available studies using a cut-off of 50 years, PFO was significantly (P = 0.001) more prevalent in younger than in older patients. CONCLUSION: Routine TEE in patients with cryptogenic IS/TIA commonly identifies abnormal findings. However, the prevalence of cardiac conditions considered to be causally associated with cerebral ischaemia (intracardiac thrombi and tumors) is low.

Safety of early endarterectomy in patients with symptomatic carotid artery stenosis: an international multicenter study.

BACKGROUND AND PURPOSE: Although the latest recommendations suggest that carotid endarterectomy (CEA) should be performed in symptomatic carotid artery stenosis (sCAS) patients within 2 weeks of the index event, only a minority of patients undergo surgery within the recommended time-frame. The aim of this international multicenter study was to prospectively evaluate the safety of early CEA in patients with sCAS in everyday clinical practice settings. METHODS: Consecutive patients with non-disabling acute ischaemic stroke (AIS) or transient ischaemic attack (TIA) due to sCAS (≥ 70%) underwent early (≤ 14 days) CEA at five tertiary-care stroke centers during a 2-year period. Primary outcome events included stroke, myocardial infarction (MI) or death occurring during the 30-day follow-up period and were defined according to the International Carotid Stenting Study criteria. RESULTS: A total of 165 patients with sCAS [mean age 69 ± 10 years; 69% men; 70% AIS; 6% crescendo TIA; 8% with contralateral internal carotid artery (ICA) occlusion] underwent early CEA (median elapsed time from symptom onset 8 days). Urgent CEA (≤ 2 days) was performed in 20 cases (12%). The primary outcomes of stroke and MI were 4.8% [95% confidence interval (CI) 1.5%-8.1%] and 0.6% (95% CI 0%-1.8%). The combined outcome event of non-fatal stroke, non-fatal MI or death was 5.5% (95% CI 2.0%-9.0%). Crescendo TIA, contralateral ICA occlusion and urgent CEA were not associated (P > 0.2) with a higher 30-day stroke rate. CONCLUSIONS: Our findings indicate that the risk of early CEA in consecutive unselected patients with non-disabling AIS or TIA due to sCAS is acceptable when the procedure is performed within 2 weeks (or even within 2 days) from symptom onset.

Extracranial venous hemodynamics in multiple sclerosis: a case-control study.

OBJECTIVES: A chronic state of impaired cerebral and cervical venous drainage, termed chronic cerebrospinal venous insufficiency (CCSVI), has recently been implicated in the pathogenesis of multiple sclerosis (MS). We performed a color-coded Doppler sonography case-control study to externally validate the CCSVI criteria. METHODS: We prospectively evaluated consecutive patients with clinically definite MS and healthy volunteers using extracranial and transcranial color-coded Doppler sonography. The recently developed neurosonology criteria for CCSVI detection were used for interpretation of ultrasound assessments. The presence of venous reflux in cervical veins was assessed both in the sitting and upright position during a short period of apnea and after Valsalva maneuver. RESULTS: We recruited 42 patients with MS (mean age 39 ± 11 years, 17 men) and 43 control individuals (mean age 38 ± 12 years, 16 men). Very good/excellent intrarater and interrater agreement (κ values 0.82-1.00) was documented in 3 out of 5 CCSVI criteria. There was no evidence of stenosis or nondetectable Doppler flow in cervical veins in patients and controls. Reflux in internal jugular vein (IJV) was documented in 1 patient (2%) and 1 control subject (2%), both in sitting and supine posture during apnea. After performing Valsalva maneuver, we documented the presence of IJV valve incompetence in 3 patients with MS (7%) and 4 healthy volunteers (9%; p > 0.999). CONCLUSIONS: With established reproducibility of venous ultrasound testing, our data argue against CCSVI as the underlying mechanism of MS. Without further independent validation of CCSVI, potentially dangerous endovascular procedures, proposed as novel therapy for MS, should not be performed outside controlled clinical trials.

Multicenter external validation of the ABCD2 score in triaging TIA patients.

OBJECTIVES: A simple clinical score (ABCD(2) score) has been introduced to triage TIA patients with a high early risk of stroke. External validation studies have yielded inconsistent results regarding the predictive ability of the ABCD(2) score. We aimed to prospectively validate the former score in a multicenter case series study. METHODS: We prospectively calculated the ABCD(2) score (age [> or = 60 years: 1 point]; blood pressure [systolic >140 mm Hg or diastolic >90 mm Hg: 1[; clinical features [unilateral weakness: 2, speech disturbance without weakness: 1, other symptom: 0]; duration of symptoms [ <10 minutes: 0, 10-59 minutes: 1, > or = 60 minutes: 2]; diabetes mellitus [yes: 1]) in consecutive TIA patients hospitalized in 3 tertiary care neurology departments across 2 different racial populations (white and Asian). RESULTS: The 7-day and 90-day risks of stroke in the present case series (n = 148) were 8% (95% CI 4%-12%) and 16% (95% CI 10%-22%). The ABCD(2) score accurately discriminated between TIA patients with high 7-day (c statistic 0.72, 95% CI 0.57-0.88) and 90-day (c statistic 0.75, 95% CI 0.65-0.86) risks of stroke. The 90-day risk of stroke was 7-fold higher in patients with an ABCD(2) score >3 points (28%, 95% CI 18%-38%) than in patients with an ABCD(2) score < or = 3 points (4%, 95% CI 0%-9%). After adjustment for stroke risk factors, race, history of previous TIA, medication use before the index TIA and secondary prevention treatment strategies, an ABCD(2) score of >2 was associated with a nearly 5-fold greater 90-day risk of stroke (hazard ratio 4.65, 95% CI 1.04-20.84, p = 0.045). CONCLUSION: Our findings externally validate the usefulness of the ABCD(2) score in triaging TIA patients with a high risk of early stroke in a multiethnic sample of hospitalized patients. The present data support current guidelines endorsing the immediate hospitalization of patients with an ABCD(2) score >2.

Stereotactic biopsy of brain stem lesions.

The successful therapy of space-occupying lesions of the brain stem, depends on precise histological diagnosis. Although the clinical management and contemporary imaging techniques (computerized tomography and magnetic resonance imaging) are now able to reveal and approach the diagnosis in these cases, only the combination of these two with the use of contemporary stereotactic systems, is able to secure the precise histological diagnosis for the patient with a good degree of safety. This study presents the first five patients in Greece with space-occupying lesions of the brain stem, in whom a stereotactic biopsy was carried out. All patients were subjected to CT-guided stereotactic biopsy, via the frontal approach in 4 patients with lesions in the superior pons and the mesencephalon and in one patient via the transcerebellar approach, for a lesion in the lateral surface of the pons. Precise histological diagnosis was possible and on the basis of a reliable choice of histological criteria the appropriate therapeutic approach was chosen, thus avoiding the old "empirical" treatment.

Tumour necrosis factor alpha is elevated in serum and cerebrospinal fluid in multiple sclerosis and inflammatory neuropathies.

Tumour necrosis factor alpha (TNFalpha) is a peptide that is derived from T lymphocytes and macrophages and is used as a marker of activated cellular immune responses. TNFalpha was measured in paired sera and cerebrospinal fluid (CSF) from 30 patients with multiple sclerosis (MS) with worsening disability, 54 patients with other neurological diseases, and 20 normal subjects. A sensitive enzyme-linked immunosorbent assay was used to determine the TNFalpha levels. We found significantly elevated serum and CSF levels in 12 (40%) and 6 (20%) MS patients, respectively, compared with healthy controls (P < 0.007 and P < 0.05). Among the 18 patients with neuropathy, we also found high serum and CSF TNFalpha values in 3 (17%) and 5 (28%) patients, respectively (P < 0.04 and P < 0.002). Our study shows that TNFalpha is probably involved in the pathogenetic mechanisms of MS and other inflammatory neurological diseases.

Cognition in relapsing-remitting multiple sclerosis: a multichannel event-related potential (P300) study.

Auditory event-related potentials (AERP) were elicited in 47 patients with relapsing-remitting (RR) multiple sclerosis (MS) and 24 age-matched controls. MS patients had significantly prolonged N2 and P3 latencies as well as low P3 amplitude compared with controls. Seven of them exceeded 3 standard deviations from the control mean values. The observed N2 and P3 alterations are associated with the patients' disability status as it is defined by the Kurtzke expanded disability status scale (EDSS), but are not related to the duration of the disease. A possible cognitive decline as reflected in the observed AERP components alterations in MS patients is subsequently discussed.

Serum IgG and IgM anticardiolipin antibodies in neurological diseases.

To determine whether anti-cardiolipin antibodies (ACA) are associated with multiple sclerosis (MS) or myasthenia gravis (MG), sera from 42 patients suffering from MS and from 21 patients with myasthenia were studied, using an enzyme-linked immunosorbent assay (ELISA). No significant difference in IgG or IgM immunoglobulin isotypes between the MS myasthenic patients and controls was found.