Eligibility for intravenous thrombolysis in acute ischemic stroke patients presenting in the 4.5-9 h window.

PURPOSE: Recent randomized-controlled clinical trials have provided preliminary evidence for expanding the time window of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients by applying certain neuroimaging criteria. We prospectively assessed the potential eligibility for IVT in the extended time window (4.5-9 h) among consecutive AIS patients treated in a comprehensive stroke center during a nine-month period. METHODS: Potential eligibility for IVT in the extended time window was evaluated by using inclusion criteria from the EXTEND trial. All patients were underwent baseline emergent neurovascular imaging using either computed tomography angiography/computed tomography perfusion (CTA/CTP) or magnetic resonance angiography/magnetic resonance perfusion (MRA/MRP). Images were post processed by the automated software RAPID. RESULTS: Our study population consisted of 317 AIS patients, and, among them, 31 (9.8 %) patients were presented in the time window of 4.5-9 h. Seven patients (2.2 %) fulfilled the EXTEND neuroimaging criteria. Four patients (1.3 %) were treated with IVT because they fulfilled both clinical and neuroimaging EXTEND criteria. Patients eligible for EXTEND neuroimaging criteria had no ischemic core lesion, whereas the mean volume of critical hypoperfusion was relatively small (17.0 ± 11.8 ml). There was no hemorrhagic complication in any of the patients treated with IVT. The median mRS score at three months was 0 (range: 0-3) among patients who were eligible for EXTEND neuroimaging criteria. CONCLUSION: Our everyday clinical practice experience suggests 9.8 % of consecutive AIS patients present in the 4.5-9 h window and 2.2 % adhere to EXTEND neuroimaging eligibility criteria for IVT. Only 1.3% of AIS is eligible for IVT according to EXTEND neuroimaging and clinical eligibility criteria.

Anti-NMDA receptor encephalitis presenting as isolated aphasia in an adult.

Anti-NMDA receptor (NMDA-r) encephalitis is a relatively rare cause of autoimmune encephalitis with divergent clinical presentations. We report a case of an adult patient with anti-NMDA-r encephalitis presenting with isolated, abrupt-onset aphasia. Her condition remained unaltered over a period of 6 months. The patients' electroencephalogram findings were typical for NMDA-r encephalitis; however, her magnetic resonance imaging and cerebrospinal fluid analysis were normal. She responded well to immunotherapy, and aphasia eventually resolved. The natural course of the present case contradicts the rapidly progressive nature of typical NMDA-r encephalitis. Furthermore, it broadens the clinical spectrum of anti-NMDA-r encephalitis, to incorporate isolated, nonprogressive aphasia.

Simple linear brainstem MRI measurements in the differential diagnosis of progressive supranuclear palsy from the parkinsonian variant of multiple system atrophy.

Differential diagnosis of progressive supranuclear palsy (PSP) and the parkinsonian variant of multiple system atrophy (MSA-P) from Parkinson's disease (PD) can be difficult, particularly in atypical cases or early in the disease course. The Magnetic Resonance Parkinsonism Index (MRPI) utilizes linear and surface (planimetry) measurements and has been proposed as a dual MRI biomarker, with high values indicative of PSP and low values of MSA. The aim of this study was to examine the utility of simple linear MRI brainstem measurements, without the use of MRI planimetry, in the diagnosis of patients with Parkinsonism and compare them to the MRPI. A total of 51 patients (PSP: 24, MSA-P: 9, PD: 18) and 15 healthy controls were included. Simple linear MRI distances of brainstem structures were measured. These included midbrain and pons diameters as well as superior cerebellar peduncle (SCP) and middle cerebellar peduncle (MCP) widths. All relevant indices, including ratios and products, were also calculated. The SCP by midbrain product (SCP × midbrain) provided improved sensitivity (100 vs. 91%) and identical specificity (98%) for the diagnosis of PSP, compared to the MRPI. Neither the MRPI nor any of the linear measurements were able to discriminate MSA-P from PD. The SCP by midbrain product is a novel, potent MRI biomarker for PSP.

Neurocognitive impairment in Whipple disease with central nervous system involvement.

Young-onset dementias pose a major challenge to both clinicians and researchers. Cognitive decline may be accompanied by systemic features, leading to a diagnosis of "dementia plus" syndromes. Whipple disease is a rare systemic illness characterized by arthralgias, chronic diarrhea, weight loss, fever, and abdominal pain. Central nervous system involvement, including severe cognitive deterioration, may precede systemic manifestations, appear during the course of the disease, or even be the only symptom. We report a previously highly functional 48-year-old man whom we first suspected of having early-onset neurodegenerative dementia but then diagnosed with Whipple disease based on a detailed clinical and laboratory evaluation. Initial neuropsychological evaluation revealed marked impairment in the patient's fluid intelligence and severe cognitive deficits in his information processing speed, complex attention, memory, visuomotor and construction dexterities, problem solving, and executive functions. At neuropsychological follow-up 21 months later, his information processing speed had improved only slightly and deficits persisted in his other cognitive functions. Repeat brain magnetic resonance imaging at that time showed that he had responded to antibiotic treatment. Because Whipple disease can cause young-onset "dementia plus" syndromes that may leave patients with neurocognitive deficits even after apparently successful treatment, we recommend comprehensive neuropsychological assessment for early detection of residual and reversible cognitive processes and evaluation of treatment response.

Evidence of an association between the scavenger receptor class B member 2 gene and Parkinson's disease.

Lysosomal protein 2 (LIMP2), the product of the scavenger receptor class B member 2 (SCARB2) gene, is a ubiquitously expressed transmembrane protein that is the mannose-6-phosphate-independent receptor for glucocerebrosidase (ß-GCase); a deficiency in this protein causes Gaucher disease. Several studies have shown a link between mutations in the ß-GCase gene and diseases characterized clinically by Parkinsonism and by the presence of Lewy body-related pathology. We hypothesized that genetic variants in the SCARB2 gene could be risk factors for Parkinson's disease (PD). A candidate-gene study of 347 Greek patients with sporadic PD and 329 healthy controls was conducted to investigate the association between 5 polymorphisms in the SCARB2 gene (rs6824953, rs6825004, rs4241591, rs9991821, and rs17234715) and the development of PD. The single-locus analysis for the 5 polymorphisms revealed an association only for the rs6825004 polymorphism: the generalized odds ratio (OR(G) ) was 0.68 (95% confidence interval [CI], 0.51-0.90), and the OR for the allelic test was OR = 0.71 (95% CI, 0.56-0.90). Haplotype analysis showed an association for the GCGGT haplotype (P < .01). Our study supports a genetic contribution of the SCARB2 locus to PD; future studies in larger cohorts are necessary to verify this finding.

Peripheral neuropathies in Sjogren syndrome: a new reappraisal.

BACKGROUND: The prevalence of peripheral neuropathy in patients with Sjögren syndrome remains unclear owing to conflicting results in the published series, with numbers ranging from 2% to over 60% of Sjögren syndrome patients. Whether peripheral neuropathy is a feature of the systemic or glandular disease or whether it is related to a circulating antineuronal antibody remains also uncertain. METHODS: The authors reviewed the records of patients with primary Sjögren syndrome (pSS), fulfilling the Revised European-American Classification Criteria, seen in their department from 1992 to 2009. The patients with previously recorded neuropathic features were re-examined clinically and electrophysiologically. Other causes of polyneuropathy were excluded. The authors also searched for circulating antineural antibodies using immunofluorescence and western blot and for antibodies against muscarinic and nicotinic acetylcholine receptors as potential biomarkers. RESULTS: 509 cases met the diagnostic criteria for pSS. Among these, 44 patients were recorded as having neuropathic symptoms. After completing the evaluation, however, only nine (1.8%) had polyneuropathy with objective clinical signs and abnormal electrophysiological findings. The neuropathy was axonal in all, in five pure sensory and in four sensorimotor. The patients with peripheral neuropathy had extraglandular manifestations such as palpable purpura and vasculitis. No evidence of antineural autoimmunity was found, and no candidate biomarkers were identified. CONCLUSION: Polyneuropathy is a rare manifestation of pSS occurring in 1.8% of patients. In the majority of patients, it is a late event and frequently associated with systemic disease or risk factors for lymphoma development.

Association between asymptomatic median mononeuropathy and diabetic polyneuropathy severity in patients with diabetes mellitus.

BACKGROUND: Asymptomatic median mononeuropathy (AMM) and diabetic polyneuropathy (DPN) often coexist and can be difficult to distinguish electrophysiologically. Moreover, the potential association between AMM and DPN has not been extensively evaluated. OBJECTIVE: We investigated the relation between AMM and DPN severity in consecutive diabetic patients. METHODS: The non-dominant limb was studied electrophysiologically in 100 consecutive diabetic patients with no symptoms of carpal tunnel syndrome on the non-dominant side. AMM was diagnosed based on previously validated electrophysiological criteria. DPN severity was graded according to the Michigan diabetic neuropathy score. RESULTS: AMM was discovered in 28% of the study population (Adjusted Wald 95% CI: 20%-37%). It was more common in women, displayed a tendency of being more common in patients over 50 years old and correlated with the severity of DPN and the number of abnormal nerves on nerve conduction studies. It was present in 18.1% of patients without evidence of DPN. No correlation was found with the duration and type of diabetes. In multivariate logistic regression models increasing severity of DPN was independently associated with the presence AMM (Wald test=10.557, df=3, p=0.014). Patients with DPN stage III and IV had a five-fold (OR=5.06, 95% CI=1.49-17.19) and a four-fold (OR=4.50, 95% CI=1.15-17.65) respectively increased likelihood to present with AMM in comparison to DPN stage I (reference group). CONCLUSIONS: Our results confirmed the high incidence of AMM in diabetic patients. AMM was present in a significant number of patients in the absence of DPN and the likelihood of AMM detection increased with increasing severity of DPN.

Intravenous Thrombolysis For Acute Ischemic Stroke in Fabry Disease.

INTRODUCTION: Fabry is a rare X-linked recessive genetic disease caused by α-galactosidase A deficiency. Cerebrovascular events occur in ∼13% of patients, whereas stroke may be the presenting clinical manifestation. There are very limited case reports of tissue plasminogen activator administration for acute ischemic stroke in patients with Fabry disease. CASE REPORT: A 46-year-old man presented with right-sided hemiparesis with a National Institutes of Health Stroke Scale score of 3. Brain computed tomography showed a hyperdense lesion resembling carvenous angioma. The patient received intravenous thrombolysis 265 minutes after symptom onset, with clinical improvement (discharge National Institutes of Health Stroke Scale score of 1). Brain magnetic resonance imaging disclosed acute thalamic infarction, cavernous angioma, and multiple cerebral microbleeds. The presence of skin angiokeratomas and cardiac hypertrophy prompted further positive investigation for Fabry disease (nondetectable α-galactosidase activity, excessively elevated lyso-Gb3, and pathogenic deletion in the GLA gene). CONCLUSION: The present case supports the scarce data underscoring the safety of intravenous thrombolysis for acute ischemic stroke in Fabry disease patients even when cerebral microbleeds are present.

Tenecteplase Averting Mechanical Thrombectomy in Emergent Large Vessel Occlusion.

INTRODUCTION: Tenecteplase has recently been studied as an alternative thrombolytic agent in acute stroke, with a possible superior effect in achieving reperfusion of large intracranial vessels. CASE REPORT: A 90-year-old female patient was admitted to our stroke unit because of acute onset of dysarthria, left-sided neglect, and hemiparesis. Brain computed tomography (CT) coupled with CT angiography and CT perfusion (postprocessed with the use of RAPID software) demonstrated right proximal middle cerebral artery occlusion with a large penumbra/small ischemic core pattern. The patient was subsequently treated with bolus tenecteplase infusion (0.25 mg/kg). Mechanical thrombectomy was abandoned because the patient has rapidly improved. The patient was discharged to her own home 4 days later with no neurological deficit and functionally independent (modified Rankin scale of 0). CONCLUSION: This case exemplifies the potential of tenecteplase in achieving swift reperfusion in patients with large vessel occlusion associated with a substantial mismatch penumbral pattern.

HLA-DRB1 differences in allelic distribution between familial and sporadic multiple sclerosis in a Hellenic cohort.

Objective: Familial Multiple Sclerosis (fMS) is reported to have distinct clinical and imaging characteristics in comparison to the sporadic disease (sMS). Nevertheless, the genetic/immunogenetic profile of fMS has never been investigated in depth, so far. In this study, we examined differences of HLA-DRB1 allelic frequencies between 57 fMS and 141 sMS Hellenic patients, with reference to 246 previously genotyped healthy controls (HCs). Patients and Methods: All patients underwent medical interview and DRB1 genotyping, using a low-resolution SSOP technique. Statistical analyses were performed using SPSS v.21.0 software, with significance set at 0.05, and p value corrected according to the Benjamini-Yekutieli method. Results: 29 fMS cases had at least one 1st degree relative affected (fMS 1st), while the rest had at least one 2nd or 3rd degree relative affected (fMS 2nd/3rd). Parent-of-origin effects were observed, with the prevalence of maternal inheritance. Frequency of DRB1*15 was significantly increased in fMS and sMS, in comparison to HCs (p = 0.002 and <0.001, respectively). After fMS stratification, this result was mainly attributed to the fMS 2nd/3rd subgroup. DRB1*11 frequency was significantly decreased only in sMS (p < 0.001) with fMS approximating HCs' frequency, especially for the fMS 1st subgroup. Heterozygosity was favored over homozygosity in all groups. Conclusion: We propose possible HLA-DRB1 allelic distribution differences between fMS and sMS, which become more apparent as proximity of affected relative/-es in fMS increases, supporting a rather degraded role of DRB1 alleles in fMS HLA/immunogenetics and indicating the concomitant implication of other HLA and non-HLA polymorphisms.

The Role of Transcranial Doppler Monitoring in Patients with Multi-Territory Acute Embolic Strokes: A Review.

Acute multi-territory, embolic cerebral infarctions are often associated with serious underlying clinical conditions including the presence of highly "active" emboligenic sources causing that in turn may result in high early recurrence rates. Prompt diagnosis, risk stratification, and treatment are substantial for the prevention of subsequent embolization that would result in further clinical deterioration. Among other clinical investigations, transcranial Doppler (TCD) monitoring is highly efficacious for the detection of microembolic signals (MES) that correspond to microthrombi entering the intracranial circulation. The presence and burden of MES, especially in multiple intracranial arteries, is clearly associated with an increased risk of symptomatic, recurrent embolization, and thus can justify a more aggressive treatment approach (clopidogrel load followed by dual antiplatelet therapy or alternatively therapeutic dose of low-molecular-weight heparin). In this narrative review, we discuss the most important causes of multi-territory embolic ischemic strokes and also underscore the utility of TCD as a noninvasive tool for the diagnosis, risk stratification, and treatment.

Familial multiple sclerosis in Greece: Distinct clinical and imaging characteristics in comparison with the sporadic disease.

OBJECTIVE: Few studies are available worldwide concerning clinical, imaging and genetic/immunogenetic profile of familial multiple sclerosis (fMS). Recent but not systematic data concerning fMS, without direct comparison to sporadic MS (sMS) drove our aim towards further research in the field, given the total lack of information for the Greek population as well. Thus, in this case-control study we examined the clinical and imaging characteristics of 102 fMS-patients, compared to 282 patients suffering sMS. PATIENTS AND METHODS: Patients recruited underwent medical interview (demographic, clinical and family history data collected). They were also assessed for disability and their MRI-scans were analyzed for lesion distribution. Statistical analyses were performed using SPSS v.21.0 software. RESULTS: 49% of unrelated fMS cases had at least one 1st degree relative affected, while the rest had also at least one relative with MS, 3rd degree or closer. Only the former subgroup (1st degree relative) and not the entire fMS sample, had significantly younger age at onset (AAO) compared to sMS cases (mean AAO 28.08 vs 31.33 years, p = 0.036). AAO anticipation was noted in younger generation fMS patients (mean AAO 24.67 years in younger generation vs 37 years in older generation, p = 0.001). With regard to our MRI findings, subcortical lesions were less frequent in fMS (71% in fMS vs 81.9% in sMS patients, p = 0.028), whereas cervical cord lesions more frequent (93% in fMS vs 79.9% in sMS patients, p = 0.033, only in the 1st degree relative subgroup). Double vision was a less common first symptom in fMS (4.1% in fMS vs 14.8% in sMS patients, p = 0.005). 1st degree relatives of fMS patients were more often diagnosed with Hashimoto's (8.9% in fMS relatives vs 3.3% in sMS relatives, p = 0.033). CONCLUSION: Younger AAO and different lesion distribution in brain and possibly spinal cord was observed in fMS in comparison to sMS patients. The hypothesis of increased genetic burden in fMS could offer some explanation for these differences, which needs though further validation as a next step, through genetic/immunogenetic testing in larger cohorts, of different ethnic groups.

The Role of Neurosonology in the Diagnosis and Management of Patients with Carotid Artery Disease: A Review.

Carotid artery disease (CAD) is a common cause of ischemic stroke with high rates of recurrence. Carotid endarterectomy (CEA) or carotid artery stenting (CAS) are highly recommended for the secondary prevention of symptomatic CAD during the first 14 days following the index event of transient ischemic attack or minor stroke. CEA or CAS may also be offered in selected cases with severe asymptomatic stenosis. Herein, we review the utility of neurosonology in the diagnosis and pre-/peri-interventional assessment of CAD patients who undergo carotid revascularization procedures. Carotid ultrasound may provide invaluable information on plaque echogenicity, ulceration, risk of thrombosis, and rupture. Transcranial Doppler or transcranial color-coded sonography may further assist by mapping collateral circulation, evaluating the impairment of vasomotor reactivity, detecting microembolization, or reperfusion hemorrhage in real time. Neurosonology examinations are indispensable bedside tools assisting in the diagnosis, risk stratification, peri-interventional monitoring, and follow-up of patients with CAD.

Novel PANK2 mutation in the first Greek compound heterozygote patient with pantothenate-kinase-associated neurodegeneration.

Pantothenate-kinase-associated neurodegeneration is the most common autosomal recessive form of neurodegeneration with brain iron accumulation. Less than 100 mutations in PANK2 gene (20p13) are responsible for classic and atypical cases. We report here the first Greek case of atypical pantothenate-kinase-associated neurodegeneration, confirmed by molecular analysis that revealed two trans-acting mutations. Our findings highlight the possible role of rare variants contributing to disease risk and possibly to variable clinical phenotype.

Early Neurological Deterioration During Alteplase Infusion for Acute Ischemic Stroke: An Uncommon Complication of Intravenous Thrombolysis.

INTRODUCTION: Recognizing new-territory ischemic stroke as an uncommon complication of intravenous thrombolysis is very important as it can lead to neurological deterioration during tissue-plasminogen-activator infusion. CASE REPORT: We report a case of an 80-year-old patient that has been treated with intravenous thrombolysis for right middle cerebral artery acute ischemic stroke. During infusion he had an abrupt neurological deterioration that proved to be a distal embolization of an asymptomatic non-occluding tip-of-the-basilar thrombus to the territory of left posterior cerebral artery that has been missed by the treating neurologist and radiologist in the pretreatment computed tomography angiography. In the thrombectomy that followed, only the right carotid artery has been catheterized and only the right middle cerebral artery was successfully recanalized, leaving the left posterior cerebral artery occlusion untreated. CONCLUSIONS: This case highlights that the use of thrombectomy in clinical practice provides an effective therapeutic option for large vessel occlusion in this setting. However, high clinical suspicion for this rare complication is mandatory to proceed to correct diagnosis and treatment.

CSF biomarkers ß-amyloid, tau proteins and a-synuclein in the differential diagnosis of Parkinson-plus syndromes.

INTRODUCTION: Differential diagnosis of Parkinson-plus patients (PSP, CBD, MSA) and Parkinson's disease (PD) patients is often not straightforward, particularly in atypical cases or at the initial stages of the diseases. Classic CSF biomarkers (amyloid-beta - Aß42, tau protein - τT and phosphorylated tau protein - τP-181) are established biomarkers in the diagnosis of Alzheimer's disease (AD). CSF a-synuclein (α-syn) has emerged as a promising biomarker in patients with Parkinsonism. The aim of this study was to analyze the CSF biochemical profile of patients with Parkinsonism. METHODS: We analyzed the CSF biomarker profile (Aß42, τT, τP-181, α-syn) and all relevant ratios in 68 patients with Parkinsonism (19 PSP, 15 MSA, 17 CBD, 17 PD) and 18 controls, diagnosed by latest established diagnostic criteria. RESULTS: CBD patients exhibited elevated τT and decreased Aß42 compared to the other groups. Five CBD, one PSP patient and one control had a typical AD CSF profile. After exclusion of these patients, the τT/Aß42 ratio was significantly elevated in MSA patients compared to PD patients and provided excellent specificity and adequate sensitivity in their differential diagnosis. CONCLUSION: CSF biochemical profile analysis is important in distinguishing AD patients with a CBS phenotype from non-AD CBS patients. The τT/Aß42 ratio is useful in the differential diagnosis of MSA from PD.