Pilot study on the probability of drug-drug interactions among direct oral anticoagulants (DOACs) and antiseizure medications (ASMs): a clinical perspective.

BACKGROUND: There is little and controversial information about changes in plasma concentrations (PCs) or clinical events during coadministration of antiseizure medications (ASMs) and direct oral anticoagulants (DOACs). We aimed to explore possible determinants of dosage class among DOACs trough PCs when ASMs are co-administered and the relative risks. We also provided some clinical examples of patients' management. METHODS: Data on adult patients concomitantly treated with ASMs (grouped in enzyme-inducing [I-ASMs], non-inducing [nI-ASMs], and levetiracetam [LEV]) and DOACs with at least one measurement of DOACs' PC were retrospectively collected. The role of DOAC-ASM combinations in predicting PC class (ranging from I at ischemic/thromboembolic risk to IV at increased bleeding risk) was investigated by an ordered logit model, and the marginal probabilities of belonging to the four dosage classes were calculated. RESULTS: We collected 46 DOACs' PCs out of 31 patients. There were 5 (10.9%) determinations in class I (4 out of 5 with concomitant I-ASMs) and 5 (10.9%) in class IV. The rivaroxaban/I-ASM combination was associated with lower DOAC dosages than rivaroxaban/LEV (OR: 0.00; 95% CI: 0.00-0.62). Furthermore, patient's probability of being in class I was approximately 50% with the rivaroxaban/I-ASM combination, while apixaban, dabigatran, and edoxaban had the highest cumulative probability of being in class II or III despite the ASM used. CONCLUSION: These preliminary results confirm the reduction of DOAC's PC by I-ASMs and suggest a better manageability of apixaban, dabigatran, and edoxaban independently from the concomitant ASM, whereas rivaroxaban seems the most liable to PC alterations with I-ASMs.

The cerebellum and visual perceptual learning: evidence from a motion extrapolation task.

Visual perceptual learning is widely assumed to reflect plastic changes occurring along the cerebro-cortical visual pathways, including at the earliest stages of processing, though increasing evidence indicates that higher-level brain areas are also involved. Here we addressed the possibility that the cerebellum plays an important role in visual perceptual learning. Within the realm of motor control, the cerebellum supports learning of new skills and recalibration of motor commands when movement execution is consistently perturbed (adaptation). Growing evidence indicates that the cerebellum is also involved in cognition and mediates forms of cognitive learning. Therefore, the obvious question arises whether the cerebellum might play a similar role in learning and adaptation within the perceptual domain. We explored a possible deficit in visual perceptual learning (and adaptation) in patients with cerebellar damage using variants of a novel motion extrapolation, psychophysical paradigm. Compared to their age- and gender-matched controls, patients with focal damage to the posterior (but not the anterior) cerebellum showed strongly diminished learning, in terms of both rate and amount of improvement over time. Consistent with a double-dissociation pattern, patients with focal damage to the anterior cerebellum instead showed more severe clinical motor deficits, indicative of a distinct role of the anterior cerebellum in the motor domain. The collected evidence demonstrates that a pure form of slow-incremental visual perceptual learning is crucially dependent on the intact cerebellum, bearing the notion that the human cerebellum acts as a learning device for motor, cognitive and perceptual functions. We interpret the deficit in terms of an inability to fine-tune predictive models of the incoming flow of visual perceptual input over time. Moreover, our results suggest a strong dissociation between the role of different portions of the cerebellum in motor versus non-motor functions, with only the posterior lobe being responsible for learning in the perceptual domain.

Analysis of combined CSF biomarkers in AD diagnosis.

BACKGROUND: The new proposed diagnostic criteria for early diagnosis of Alzheimer's Disease (AD) underline the value of cerebrospinal fluid (CSF) biomarkers. The first aim of the study was to determine the diagnostic accuracy of CSF biomarker Abeta1-42, T-tau, and P-tau in differentiating AD patients in our cohort by means of "pure" biomarkers and in form of a combined analysis of these biomarkers. The second aim of the study was to determine the diagnostic accuracy of these markers for predicting incipient AD in patients with mild cognitive impairment (MCI). METHODS: We studied 102 CSF samples: 33 AD [mean age at baseline 71.2 (54-86)], 16 MCI [mean age at baseline 71.3 (57-78)], 24 non AD dementia, including 7 vascular dementia, 4 frontotemporal degeneration, 5 dementia with Lewy Body, and 8 with other dementia [mean age at baseline 72.7 (51-87)] and 32 non-demented neurological patients [mean age at baseline 71.3 (45-87) referred to as control (CO) later in the text]. A double sandwich ELISA (Innotest beta amyloid Abeta1-42, hTau and P-tau181 by Innogenetics, Gent, Belgium) was performed to quantify the concentration of the above biomarkers. The three biomarkers were then combined in the IATI index [(measured Ab1-42)/(240 + 1.18 *measured tau)], and in the ratios Abeta1-42/T-tau, Abeta1-42/P-tau, T-tau/Abeta1-42 and P-tau/Abeta1-42. RESULTS: Abeta1-42, T-tau and P-tau181 concentration showed statistically significant differences between AD and CO (327.2 pg/mL +/- 150.2 pg/mL and 659.4 pg/mL +/- 254.2 pg/mL; 508.2 pg/mL +/- 360.2 pg/mL and 305.3 pg/mL +/- 228.9 pg/mL; 82.2 pg/mL +/- 26.1 pg/mL and 45.3 pg/mL +/- 26.4 pg/mL, respectively, p < 0.05), while the difference between AD and MCI was statistically different only for Abeta1-42 (327.2 pg/mL +/- 150.2 pg/mL and 600.8 +/- 271.9 pg/mL, respectively, p < 0.05). The IATI index was 0.5 +/- 0.3 in AD, 0.9 +/- 0.6 in MCI, 1.37 +/- 0.9 in non AD dementia and 1.26 +/- 0.8 in non-demented neurological patients. With a cut-off fixed at 1 the sensitivity and specificity of the IATI index in discriminating AD from CO was 84% and 52%, respectively. CONCLUSIONS: This study confirms the great significance of CSF biomarker measurements in AD diagnosis in clinical routine. It is understood that a clinical diagnostic work-up is necessary in the process. Moreover, a biochemical profile of CSF biomarkers requires further investigations.

Does statin in the acute phase of ischemic stroke improve outcome after intravenous thrombolysis? A retrospective study.

BACKGROUND: In recent years, the medical literature has shown that statin treatment before and in the acute phase of ischemic stroke has a positive impact on outcome. The possible effect of statins during the acute phase has never been assessed in thrombolysed patients, and the few studies investigating a possible association between prior statin use and outcome after thrombolysis have reported controversial results. The aim of the present study was to assess whether statin treatment started in the acute phase of stroke (within 24h) or before stroke and continued during the acute phase may influence short- and long-term outcome in patients receiving intravenous (IV) thrombolysis. METHODS: We conducted a retrospective analysis of 250 patients treated with IV thrombolysis. Outcome measures were 3-month good functional outcome (modified Rankin Scale ≤ 2); neurological improvement (reduction ≥ 4 points on the National Institutes of Health Stroke Scale [NIHSS]) between 24 and 72 h; and symptomatic intracerebral hemorrhage (brain hematoma associated with NIHSS deterioration ≥ 4 points) within 72 h. RESULTS: Multivariate analysis showed that statin treatment started in the acute phase of stroke was associated with both good functional outcome (OR: 6.18; 95% CI: 1.43-26.62; P=0.015) and neurological improvement (OR: 9.47; 95% CI: 1.98-45.37; P=0.005), whereas statin treatment started before stroke and continued in the acute phase was associated with symptomatic intracerebral hemorrhage (OR: 6.65; 95% CI: 1.58-29.12; P=0.010). CONCLUSIONS: Our data suggest that statin treatment started within 24h after IV thrombolysis, but not statin treatment started before stroke and continued in the acute phase, may improve short- and long-term outcome.

Ataxia in posterior circulation stroke: clinical-MRI correlations.

OBJECTIVE: Ataxia is characterized clinically by four signs (gait and limb ataxia, dysarthria and nystagmus). Although ataxia has been described in posterior circulation (PC) stroke series, there are no prospective studies that have investigated a possible differential role of the cerebellum or its input/outputs in causing ataxia. METHODS: Ataxia was semi-quantified according to the International Cooperative Ataxia Rating Scale (ICARS) in 92 consecutive patients with acute PC stroke. Four topographical patterns based on magnetic resonance imaging (MRI) findings were identified: picaCH pattern (posterior inferior cerebellar artery infarct); scaCH pattern (superior cerebellar artery infarct); CH/CP pattern (infarct involving both the cerebellum and the brainstem cerebellar pathways); and CP pattern (infarct involving the brainstem cerebellar pathways). RESULTS: Gait ataxia was present in 95.7%, limb ataxia in 76.1%, dysarthria in 56.5% and nystagmus in 65.2% of patients. Gait ataxia frequency did not differ between the patterns, but was significantly more severe in the CH/CP pattern than in either picaCH (P=0.0059) or CP (P=0.0065) pattern. Limb ataxia was significantly less frequent (P<0.001) and less severe (P<0.001) in picaCH pattern than other patterns. Dysarthria was less frequent in picaCH pattern than in other patterns (P=0.018) and less severe than in scaCH (P=0.0043) or CP (P=0.0047) pattern. No differences in nystagmus frequency or severity were observed across all four patterns. CONCLUSION: In PC stroke gait ataxia was almost always present, regardless of the lesion site. Limb ataxia and dysarthria were less frequent in the picaCH pattern, whereas nystagmus, when present, did not differ among the topographical patterns.

Abduction finger sign: a new sign to detect unilateral functional paralysis of the upper limb.

Objective of this study is testing a new sign to differentiate functional from organic paralysis of the arm. Thirty-six healthy subjects, ten patients with acute functional paralysis of one arm and eleven patients with acute organic paralysis of one arm were enrolled. The test consisted of abduction finger movements of one hand against resistance with a maximal sustained contraction to detect synkinetic abduction finger movements of the contralateral hand. For both hands, contralateral hand synkinesias were observed in healthy subjects. The task performed with the unaffected hand evoked synkinesias of the presumed affected hand in functional patients, but did not evoke synkinesias of the affected hand in organic patients. The abduction finger test had 100% sensitivity and specificity in distinguishing functional from organic paralysis of the upper limb in this cohort of patients. The abduction finger sign may be a reliable bedside test to discriminate functional from organic arm paralysis.

Focal motor seizures mimicking hemifacial spasm.

A young female patient, who presented acutely with an unusual movement disorder characterized by hyperkinetic facial movements, was referred to us for hemifacial spasm. The only abnormality on neurological examination was myoclonus of the left perioral and bilateral periorbital muscles, exacerbated by mental tasks. A week later, the patient also presented two generalized tonic-clonic seizures on awakening and was successfully treated with antiepileptic drugs. Laboratory and neuroimaging investigations yielded normal findings. Although we were unable to identify a cortical generator, the concomitant occurrence of generalized seizures, the disappearance of symptoms after treatment and the topography of the myoclonus support an epileptic origin of this myoclonus.

Limb ataxia and proximal intracranial territory brain infarcts: clinical and topographical correlations.

BACKGROUND: Limb ataxia is classically attributed to cerebellar hemispheric lesions, although isolated lesions of the inferior cerebellar peduncle (ICP) in the medulla may also cause this sign. It is still unclear why only some patients with acute cerebellar infarcts in the posterior inferior cerebellar artery (PICA) territory present with limb ataxia. The proximal intracranial posterior circulation (P-PC) territory includes structures fed by the intracranial vertebral arteries (ICVAs): the medulla, supplied by small ICVAs branches, and posterior inferior portion of the cerebellum, fed by PICA. ICP and PICA territory cerebellar infarcts most often occur independently but occasionally occur together. OBJECTIVE: To identify structures responsible for limb ataxia in acute P-PC brain infarcts, correlating clinical and topographical findings. METHODS: Sixteen patients (8 women) were included, aged 30-82 years (mean 62 years), with isolated acute strokes in the P-PC territory. RESULTS: The cases reported here indicate that limb ataxia in acute P-PC territory infarcts may be associated with damage to the ICP in the dorsolateral medulla, regardless of a hemispheric cerebellar lesion. In fact, among the nine patients with PICA stroke, limb ataxia was observed only in the two patients who also presented damage to the dorsolateral medulla involving the ICP. Of the seven patients with isolated dorsolateral medullary infarct, only five patients with ICP damage had limb ataxia. CONCLUSIONS: When correlating limb ataxia and acute P-PC infarcts, it is important to take into account the entire ICVA territory.