Early predictors of dysphagia in ischaemic stroke patients.

BACKGROUND AND PURPOSE: Post-stroke dysphagia affects outcome. In acute stroke patients, the aim was to evaluate clinical, cognitive and neuroimaging features associated with dysphagia and develop a predictive score for dysphagia. METHODS: Ischaemic stroke patients underwent clinical, cognitive and pre-morbid function evaluations. Dysphagia was retrospectively scored on admission and discharge with the Functional Oral Intake Scale. RESULTS: In all, 228 patients (mean age 75.8 years; 52% males) were included. On admission, 126 (55%) were dysphagic (Functional Oral Intake Scale ≤6). Age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05), pre-event modified Rankin scale (mRS) score (OR 1.41, 95% CI 1.09-1.84), National Institutes of Health Stroke Scale (NIHSS) score (OR 1.79, 95% CI 1.49-2.14), frontal operculum lesion (OR 8.53, 95% CI 3.82-19.06) and Oxfordshire total anterior circulation infarct (TACI) (OR 1.47, 95% CI 1.05-2.04) were independently associated with dysphagia at admission. Education (OR 0.91, 95% CI 0.85-0.98) had a protective role. At discharge, 82 patients (36%) were dysphagic. Pre-event mRS (OR 1.28, 95% CI 1.04-1.56), admission NIHSS (OR 1.88, 95% CI 1.56-2.26), frontal operculum involvement (OR 15.53, 95% CI 7.44-32.43) and Oxfordshire classification TACI (OR 3.82, 95% CI 1.95-7.50) were independently associated with dysphagia at discharge. Education (OR 0.89, 95% CI 0.83-0.96) and thrombolysis (OR 0.77, 95% CI 0.23-0.95) had a protective role. The 6-point "NOTTEM" (NIHSS, opercular lesion, TACI, thrombolysis, education, mRS) score predicted dysphagia at discharge with good accuracy. Cognitive scores had no role in dysphagia risk. CONCLUSIONS: Dysphagia predictors were defined and a score was developed to evaluate dysphagia risk during stroke unit stay. In this setting, cognitive impairment is not a predictor of dysphagia. Early dysphagia assessment may help in planning future rehabilitative and nutrition strategies.

Etiologic reclassification of cryptogenic stroke after implantable cardiac monitoring and computed tomography angiography re-assessment.

INTRODUCTION: Different mechanisms may underlie cryptogenic stroke, including subclinical atrial fibrillation (AF), nonstenotic carotid plaques (NCP), and aortic arch atherosclerosis (AAA). In a cohort of cryptogenic stroke patients, we aimed to: (1) evaluate the prevalence of subclinical AF, NCP, and AAA, and reclassify the etiology accordingly; (2) compare the clinical features of patients with reclassified etiology with those with confirmed cryptogenic stroke. METHODS: Data of patients hospitalized for cryptogenic stroke between January 2018 and February 2021 were retrospectively analyzed. Patients were included if they received implantable cardiac monitoring (ICM) to detect subclinical AF. Baseline computed tomography angiography (CTA) was re-evaluated to assess NCP and AAA. Since aortic plaques with ulceration/intraluminal thrombus were considered pathogenetic during the initial workup, only patients with milder AAA were included. Stroke etiology was reclassified as "cardioembolic", "atherosclerotic", or "mixed" based on the detection of AF and NCP/AAA. Patients with "true cryptogenic" stroke (no AF, ipsilateral NCP, or AAA detected) were compared with those with reclassified etiology. RESULTS: Among 63 patients included, 21 (33%) were diagnosed with AF (median follow-up time of 15 months), 12 (19%) had ipsilateral NCP, and 6 (10%) had AAA. Stroke etiology was reclassified in 30 patients (48%): cardioembolic in 14 (22%), atherosclerotic in 9 (14%), and mixed in 7 (11%). Patients with true cryptogenic stroke were younger compared to those with reclassified etiology (p = 0.001). DISCUSSION: One or more potential covert stroke sources can be recognized in half of the patients with a cryptogenic stroke through long-term cardiac monitoring and focused CTA re-assessment.

Predictivity of the clock drawing test in the acute phase of cerebrovascular diseases on cognitive decline at a 6-month neuropsychological evaluation.

INTRODUCTION: We showed that the Clock Drawing Test (CDT) performed during the acute phase of cerebrovascular diseases predicted worsening of cognitive function defined based on a clinical judgement at a 3-month follow-up. The aim of this study was to verify the predictivity of the CDT on the worsening of cognitive status assessed with an extensive neuropsychological evaluation 6 months after the acute event. METHODS: Patients with a stroke or transient ischemic attack underwent a baseline clinical, neuroimaging, and neuropsychological assessment, including the CDT. Premorbid cognitive status was evaluated by means of the Clinical Dementia Rating scale. Between 6 and 7 months after the acute event, all patients underwent a neuropsychological evaluation that included tests for executive function, attention, language, memory, and visuospatial abilities. RESULTS: Fifty patients (29 males; mean age 72.2 years) were enrolled: 28 (56%) had no premorbid cognitive impairment, 15 (30%) had premorbid mild cognitive impairment (MCI), and 4 (8%) had premorbid dementia; for 3 patients, evaluation of premorbid status was not available. At follow-up, 11 (22%) had no cognitive impairment, 28 (56%) were diagnosed with MCI, and 11 (22%) dementia. In patients who were non-demented before the event, on regression analysis, the score obtained at CDT was predictive of decline of cognitive status at the 6-month follow-up (OR 1.65; 95% CI 1.08-2.52). DISCUSSION: Our study confirms that administering the CDT during the acute phase of cerebrovascular diseases is informative with regard to the worsening of cognitive function after 6 months.

The Clock Drawing Test as a predictor of cognitive decline in non-demented stroke patients.

BACKGROUND: The early detection of patients at risk of post-stroke cognitive impairment (PSCI) may help planning subacute and long-term care. We aimed to determine the predictivity of two screening cognitive tests on the occurrence of mild cognitive impairment or dementia in acute stroke patients. METHODS: A cognitive assessment within a few days of ischemic or hemorrhagic stroke was performed in patients consecutively admitted to a stroke unit over 14 months by means of the Clock Drawing Test (CDT) and the Montreal Cognitive Assessment-Basic (MoCA-B). RESULTS: Out of 191 stroke survivors who were non-demented at baseline, 168 attended at least one follow-up visit. At follow-up (mean duration ± SD 12.8 ± 8.7 months), 28 (18.9%) incident cases of MCI and 27 (18%) cases of dementia were recorded. In comparison with patients who remained cognitively stable at follow-up, these patients were older, less educated, had more comorbidities, a higher score on the National Institutes of Health Stroke Scale (NIHSS) at admission, more severe cerebral atrophy, and lower MoCA-B and CDT scores at baseline. In multi-adjusted (for age, education, comorbidities score, NIHSS at admission and atrophy score) model, a pathological score on baseline CDT (< 6.55) was associated with a higher risk of PSCI at follow-up (HR 2.022; 95% CI 1.025-3.989, p < 0.05) with respect to non-pathological scores. A pathological baseline score on MoCA-B (< 24) did not predict increased risk of cognitive decline at follow-up nor increased predictivity of stand-alone CDT. CONCLUSION: A bedside cognitive screening with the CDT helps identifying patients at higher risk of PSCI.

Neuropsychological screening in the acute phase of cerebrovascular diseases.

INTRODUCTION: Cognitive impairment is a common and disabling consequence of stroke. Its prevalence, the best way to screen for it in the acute setting, and its relation with premorbid status have not been thoroughly clarified. MATERIALS AND METHODS: Ischemic and hemorrhagic stroke patients admitted to our stroke unit underwent a baseline assessment that included a clinical and neuroimaging assessment, two cognitive tests (clock-drawing test, CDT; Montreal Cognitive Assessment-Basic, MoCA-B) and measures of premorbid function (including the Clinical Dementia Rating Scale). A follow-up examination was repeated 3-4 months after the acute event. RESULTS: Two hundred and twenty-three patients (52.5% women, mean age ± SD 75.8 years ± 12.3) were evaluated. Prestroke cognitive impairment was present in 91 patients (40.8%). At follow-up, the prevalence of cognitive impairment was 49%, while its incidence among patients who did not have any prestroke cognitive impairment was 38.8%. Of the originally admitted 223 patients (71 were lost to follow-up), only 60 (26.9%) were still cognitively intact at follow-up. On regression analysis, age and baseline CDT were associated with worsening of cognitive status at follow-up. In patients without cognitive impairment at baseline, a cutoff of 23 for MoCA-B and of 8.7 for CDT scores predicted the diagnosis of post-stroke cognitive impairment with sufficient accuracy. DISCUSSION AND CONCLUSION: Prestroke and post-stroke cognitive impairment affect a large proportion of patients with stroke. Our findings suggest that a neuropsychological screening during the acute phase might be predictive of the development of post-stroke cognitive impairment.

Ischemic stroke caused by giant cell arteritis associated with pulmonary adenocarcinoma.

Giant cell arteritis (GCA) is the most common vasculitis in patients older than 50 years, and it is occasionally a cause of ischemic stroke. GCA as a paraneoplastic manifestation has been rarely described. We describe a 77-year-old man with a sudden onset of dizziness, vomiting, and gait disturbances. Following imaging studies, a diagnosis of bulbar ischemic stroke with left vertebral artery stenosis was made. Based on a history of polymyalgia rheumatica, on laboratory tests, and brain digital subtraction angiography, a diagnosis of GCA was advanced and the patient underwent high-dose steroidal therapy. After a total body 18-FGD PET imaging, a pulmonary adenocarcinoma was found. Vertebral artery involvement is a rare but important occurrence in GCA as it carries a high mortality rate, and may require a vigorous therapeutic approach. The association of lung cancer and GCA is infrequent, and the relationship between malignancy and GCA remains unclear. Whereas the search for a malignancy in the setting of a GCA is not routinely performed, the use of total body PET when a large vessel vasculitis is suspected may provide useful information on disease and help recognize occult neoplasms.

Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention.

Background and Purpose- Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non-vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods- Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results- Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95-5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63-9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83-3.16), and CHA2DS2-VASc score (OR, 1.72 for each point increase; 95% CI, 1.58-1.88) were associated with ischemic events. Among the CHA2DS2-VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33-0.61). Conclusions- In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA2DS2-VASc score were associated with increased risk of cerebrovascular events.

Neuroanatomical, Clinical and Cognitive Correlates of Post-Stroke Dysphagia.

BACKGROUND AND PURPOSE: About half of the dysphagic stroke patients have persistent swallowing dysfunction after 7 days from symptom onset. The aim of the study was to evaluate incidence, prognosis, clinical and neuroradiological correlates of post-stroke dysphagia. METHODS: We prospectively examined consecutive patients with acute ischemic or hemorrhagic stroke. Patients' clinical and neuroradiological data were collected. Swallowing function was assessed by the water swallow test upon admission and after 14 days; patients were then classified as persistent dysphagic, non-persistent dysphagic or non-dysphagic. RESULTS: We recruited 275 patients, 121 of whom were dysphagic upon admission and 254 patients attended follow-up at 14 days; 141 never presented dysphagia, 21 had a non-persistent pattern of dysphagia and 92 had a persistent one. Stroke type, leukoaraiosis degree, previous cognitive impairment and stroke severity upon admission independently predicted the occurrence of dysphagia after stroke and its persistence as well. At receiver operating characteristic (ROC) analysis, the National Institutes of Health Stroke Scale (NIHSS) score of 11.5 was the best predictive value of persistent dysphagia, with a specificity of 90.1% and a sensitivity of 72.4%. CONCLUSION: Stroke severity is an important predictor of a persistent pattern of dysphagia, with a suggested NIHSS cutoff value of ≥12. An independent correlation was observed with leukoaraiosis and with previous cognitive impairment.

APOE ε2 and ε4 influence the susceptibility for Alzheimer's disease but not other dementias.

Apolipoprotein E (APOE) genotype was determined in a population of patients with dementia, including 735 patients with Alzheimer's disease (AD), 75 with Frontotemporal Lobar Degeneration (FTLD), 97 with Vascular Dementia (VaD) and 40 with Lewy Body Dementia (LBD), as well as in 506 age- and gender-matched controls (CON). APOE ε2 allele frequency was lower in patients with AD (2.8%) than in CON (6.4%, P≤0.001, OR: 0.41). Similar results were obtained comparing AD with FTLD (6.7%, P≤0.01, OR: 0.37), at difference from VaD (5.6%, P>0.05) or LBD (5.0%, P>0.05). The frequency of the APOE ε4 allele was increased in patients with AD (25.1%) as compared with CON (8.2%, P≤0.001, OR: 4.24), FTLD (11.3%, P≤0.001, OR: 2.67), VaD (11.8%, P≤0.001, OR: 3.02), or LBD (13.8%, P=0.048, OR: 2.07). The frequency of the ε4/ε4 genotype was increased in AD patients compared with controls (6.3 versus 0.8%, P≤0.001, OR: 8.38). The presence of the ε2 allele is a protective factor for AD, whereas the ε4 allele acts as a risk factor for the disease. Both alleles do not influence the susceptibility to FTLD, LBD and VaD.

Sleep and headache: a bidirectional relationship.

Sleep and pain perception are two phylogenetically well-conserved functions, strictly influenced by environmental and psychological factors, and are able to interact reciprocally both in physiological and pathological situations. Sleep and head-pain perception share the involvement of several structures, such as the thalamus, the hypothalamus and brainstem nuclei, including the locus coeruleus and raphe nuclei. There ais clinical evidence indicating that sleep disorders can precede the appearance of certain headaches and that head pain, especially when frequent, can, in turn, affect sleep quality. In the present work the anatomy, physiology and pathology of sleep and head-pain perception will be reviewed with the aim of highlighting the points of contact and possible unifying treatment strategies.

Allodynia in migraine: frequent random association or unavoidable consequence?

Allodynia, the perception of pain induced by a non-painful stimulus, is frequently associated with migraine, especially when chronic, and mainly in the aura subtype. Among migraineurs, allodynia is thought to be caused by the headache and the activation of nociceptors with the development of central sensitization in subjects with an altered regulation of the central nociceptive pathway. The persistence of pain sensation seems to be able to induce central sensitization in the caudal nucleus of the trigeminal nerve by lowering the neuronal pain threshold. Different pathogenetic mechanisms may be involved and genetic, environmental and psychological elements should be considered. The complaint of allodynia is more frequent during the headache attack (acute allodynia) than in-between attacks (interictal allodynia). Acute allodynia is generally referred to the painful region but may diffuse to other areas, cephalic or even extracephalic. Extracephalic allodynia could not be mediated by nucleus caudalis as its neurons do not express whole-body receptive fields. The likely mechanism is thalamic sensitization. This symptom must be carefully assessed because it may be as annoying and limiting in daily activities as pain itself, and because its presence seems to reduce the efficacy of drugs used for migraine attacks. Instrumental measures may be applied, and clinical questionnaires to assess the presence of allodynic symptoms have also been developed and validated. All these aspects will be discussed.

Acute and interictal allodynia in patients with different headache forms: an Italian pilot study.

OBJECTIVE: To investigate allodynia in patients with different primary headaches. BACKGROUND: Many migraineurs have allodynia during headache attacks; some may have allodynia outside attacks; allodynia may also be associated with other primary headaches. METHODS: A total of 260 consecutive primary headache patients presenting for the first time at a headache center, and 23 nonheadache controls answered written questions (subsequently repeated verbally) to determine the presence of acute and interictal allodynia. RESULTS: We divided the patients into: episodic migraine (N = 177), subdivided into only migraine without aura (N = 114) and those sometimes or always reporting migraine with aura (N = 63); episodic tension-type headache (N = 28); chronic headaches (headache > or = 15 days/month, N = 52), including chronic migraine, chronic tension-type headache, and medication-overuse headache; and other headache forms (N = 3). Acute allodynia was present in 132 (50.7%), significantly more often in patients sometimes or always suffering migraine with aura, and those with chronic headache forms, compared to patients with migraine without aura and episodic tension-type headache. Interictal allodynia was present in 63 (24.2%) patients, with significantly higher frequency in those having migraine with aura attacks than controls and common migraine patients. CONCLUSIONS: Allodynia is not specific to migraine but is frequent in all headache patients: acute allodynia was reported in half those interviewed and in over a third of patients in each headache category; interictal allodynia was reported by nearly 25%.

Serum folate concentrations in patients with cortical and subcortical dementias.

Folic acid is believed to play a role in protection from oxidant stress. Low levels of folic acid had been found in serum from patients with Alzheimer disease (AD). Folate concentration was evaluated in sera from 136 patients with cortical dementia [AD, n=108; frontotemporal dementia (FTD), n=28], 57 patients with subcortical dementia [Lewy body disease (LBD), n=9; corticobasal degeneration (CBD), n=5; progressive supranuclear palsy (PSP), n=6; Parkinson disease with dementia (PD-Dem), n=37], and 76 nondemented, healthy age-matched people. Serum folic acid levels were decreased in patients with AD and FTD as compared with either controls or patients with subcortical dementia (3.60+/-2.22 and 5.37+/-2.92 microg/L versus 6.87+/-3.50 microg/L, respectively; P<0.01). A tendency towards decreased folate concentration was found in LBD and CBD, but not to a significant extent. The highest proportion of folate-deficient patients was found in CBD, FTD and AD (respectively, 60, 48.2 and 46.3% versus 7.9% in controls; P<0.001). Folate deficiency characterizes FTD as well as AD. These differences observed among different clinical dementing syndromes may be related to neocortical damage.

Plasma levels of beta-amyloid (1-42) in Alzheimer's disease and mild cognitive impairment.

We compared plasma levels of beta-amyloid 1-42 (pg/ml) found for 146 sporadic Alzheimer (AD) patients, 89 subjects with mild cognitive impairment (MCI) and 89 age-matched controls (CT). AD patients had significantly lower levels (38, 54, 52; p<0.01), unrelated to severity of the disease as assessed by MMSE score, age, sex or APOE4 status. Twenty cases investigated at two time points 18 months apart did not demonstrate further decreases. Thus, the reduction in beta-amyloid 1-42 may be a marker for AD status, specifically, a transition from normal status or MCI to AD, rather than a marker for neurodegenerative processes occurring in the disease.

A novel polymorphism in SEL1L confers susceptibility to Alzheimer's disease.

Alzheimer's disease (AD) is considered to be a conformational disease arising from the accumulation of misfolded and unfolded proteins in the endoplasmic reticulum (ER). SEL1L is a component of the ER stress degradation system, which serves to remove unfolded proteins by retrograde degradation using the ubiquitin-proteosome system. In order to identify genetic variations possibly involved in the disease, we analysed the entire SEL1L gene sequence in Italian sporadic AD patients. Here we report on the identification of a new polymorphism within the SEL1L intron 3 (IVS3-88 A>G), which contains potential binding sites for transcription factors involved in ER-induced stress. Our statistical analysis shows a possible role of the novel polymorphism as independent susceptibility factor of Alzheimer's dementia.