Pitfall of Light Transmission Aggregometry-Based Assessment of Platelet Function in Acute Ischemic Stroke Patients.

BACKGROUND: The utility of light transmission aggregometry (LTA)-based assessment of platelet function in acute ischemic stroke patients remains controversial. This study aimed to clarify why LTA failed to estimate platelet function in acute ischemic stroke patients. METHODS: Using LTA, we evaluated the platelet aggregation abilities of citrated blood samples from 22 acute noncardiogenic ischemic stroke patients prior to treatment and compared them with those of 65 heathy volunteer controls. Platelet counts and mean platelet volumes (MPV) of citrated blood and platelet-rich plasma (PRP) prepared for LTA were evaluated simultaneously. Using a hematology analyzer, we also measured and compared the aggregation-prone properties of platelets in the hematology analysis process between patient and control samples. RESULTS: Although platelets aggregated more easily and frequently in patient samples (P < .01), the maximum aggregation rate (MA%) of LTA was paradoxically lower in patients than in controls (P < .05). The PRP/citrated blood ratio of platelet counts and MPV were significantly lower in patients than in controls (P < .05). CONCLUSIONS: Our results suggest that MA% of LTA is erroneously displayed as lower values than the actual status in patients with increased platelet aggregation ability such as acute ischemic stroke because activated large platelets are preaggregated and thus decreased in the PRP on LTA.

Influence of Platelet Aggregate Formation in Blood Samples on Light Transmission Aggregometry Results.

BACKGROUND: Light transmission aggregometry is a standard method used to evaluate platelet function. However, in clinical settings, light transmission aggregometry results sometimes fail to reflect actual platelet hyperactivity. In patients with suspected platelet hyperactivity such as thrombosis, platelet aggregates are frequently detected in citrated blood samples using a scattergram of a hematology analyzer. This study aimed to evaluate the effects of platelet aggregate formation on light transmission aggregometry results. METHODS: We used 19 citrated blood samples in which platelet aggregate formation was intentionally induced by a hematology analysis process. Employing fully automated light transmission aggregometry and agonists including adenosine diphosphate or collagen, light transmission aggregometry maximum aggregation percentage, platelet count, and mean platelet volume of platelet-rich plasma before and after platelet aggregate formation were evaluated. RESULTS: Light transmission aggregometry maximum aggregation percentage with adenosine diphosphate or collagen was significantly lower in the samples after than before platelet aggregate formation. Platelet count and mean platelet volume were both decreased by platelet aggregate formation (P < .01), suggesting that maximum aggregation percentage reduction was caused by the decrease in activated large platelets in the platelet-rich plasma. CONCLUSION: This study clarified that platelet aggregate formation in blood samples interfered with an accurate assessment of platelet hyperactivity. To ensure reliability of light transmission aggregometry results, we must confirm that platelet aggregates have not formed in the sample, especially in those of patients with platelet hyperactivity.

Adduction-Abduction Asymmetry in Saccades During Video-Oculographic Monocular Recording: A Word of Caution.

In eye movement examination, video-oculographic monocular recording has become more popular than electro-oculographic binocular recording. The aim of this study was to examine the characteristics of monocular movements recorded using video-oculography. In 66 healthy subjects, the horizontal saccades and smooth pursuit eye movements of the right eye within a range of 30º were evaluated using a video-oculographic eye movement recording system. Saccade latency, velocity, accuracy, and smooth pursuit gain were measured and analysed by age and direction. Saccade parameters (latency, velocity, and amplitude) and smooth pursuit gain deteriorated with age in healthy subjects. Saccade velocity and accuracy were significantly larger during adduction than during abduction. The smooth pursuit gain did not differ between adduction and abduction. In conclusion, unlike smooth pursuit eye movements, saccadic eye movements have adduction-abduction asymmetry. In video-oculographic monocular recording of saccades, it is necessary to recognise the possibility of the existence of adduction-abduction asymmetry.

Isolated Unilateral Ptosis due to Paramedian Midbrain Infarction.

A 59-year-old man who had hypertension, dyslipidemia, diabetes mellitus, and left eye glaucoma developed sudden vertigo and left ptosis; he did not notice diplopia. He visited our hospital on day 3 after onset and neurologic examination showed left ptosis. His left visual acuity was counting fingers, and the light reflex was sluggish owing to glaucoma. Pupil sizes were equal, and eye movements and the lower lid were unremarkable. Magnetic resonance images revealed an acute infarction of the left paramedian midbrain. We considered that selective damage to the oculomotor fascicles innervating the left levator palpebrae superioris caused ipsilateral ptosis. As the fascicles for this ocular muscle run in the small area adjacent to those for the medial rectus, inferior rectus and superior rectus muscles, this is an extremely rare case of midbrain infarction presenting with isolated unilateral ptosis.

Antiplatelet Loading Effects Prior to Endovascular Treatment: Carotid Artery Stenosis versus Unruptured Cerebral Aneurysms.

Objective: Carotid artery stenosis and cerebral aneurism may have different platelet functions and antiplatelet responses because these diseases have different etiologies. In this study, we compared the antiplatelet loading effects prior to endovascular treatment between carotid artery stenosis and unruptured cerebral aneurysm (UCA) patients. Methods: Nine patients with asymptomatic carotid artery stenosis (ACS), 14 with symptomatic carotid artery stenosis (SCS), and 20 with unruptured cerebral aneurysms were enrolled in this study. Antiplatelet (aspirin + clopidogrel) loading effects prior to endovascular treatment were evaluated using light transmission aggregometry and platelet aggregate detection methods. Results: Although there are differences in the prevalence of atherosclerosis risk factors, maximum aggregation rates in light transmission aggregometry and platelet aggregation-prone properties were not different in the three disease groups. Conclusion: Preoperative dual antiplatelet therapy with aspirin and clopidogrel may be appropriate for both carotid artery stenosis and cerebral aneurism patients even though their conditions and background factors differ.

Bedside video-oculographic evaluation of eye movements in acute supratentorial stroke patients: A potential biomarker for hemispatial neglect.

BACKGROUND AND PURPOSE: The presence of hemispatial neglect adversely affects functional outcomes in stroke patients; consequently, it warrants early targeted rehabilitative intervention. Nevertheless, hemispatial neglect in the acute phase of stroke has often been underdiagnosed. In this study, we aimed to detect hemispatial neglect at the bedside in acute stroke patients by measuring eye movements using video-oculography (VOG). METHODS: Forty-seven patients with acute unilateral supratentorial stroke were enrolled. We quantitatively measured horizontal saccade (latency, velocity, and amplitude) and smooth pursuit (gain) at the bedside using VOG and compared these variables with scores on the Behavioral Inattention Test (BIT), a screening battery to assess hemispatial neglect. RESULTS: Contralesional saccade latency, velocity, and amplitude, and ipsilesional smooth pursuit gain were suppressed compared with those in the opposite directions (p = 0.08, 0.02, 0.04, and 0.02, respectively). These directional ocular hypokinesia values correlated with the total BIT score (correlation coefficients -0.53, 0.48, 0.51, and 0.39, respectively). The association was significant even after adjusting for age and stroke severity. CONCLUSIONS: Eye movement measurements performed using VOG significantly correlated with the tendency for hemispatial neglect in acute supratentorial stroke patients. Bedside VOG measurement may be a simple biomarker for detecting hemispatial neglect even in patients in the supine position during the acute phase of stroke.

Effects of uncomfortable care and histamine H2-antagonists on delirium in acute stroke: A propensity score analysis.

BACKGROUND AND PURPOSE: Uncomfortable care and histamine H2 antagonist (H2A) are implicated in precipitating delirium. In acute stroke, however, the need for them depends on stroke severity, an established risk factor for delirium. So, it is unclear whether care or H2A itself is responsible for delirium. We aimed to evaluate their causal effects on delirium in acute stroke patients. METHODS: This is a prospective cohort study on acute stroke patients admitted to a stroke care unit. Patients without stupor, coma, sedation, or delirium upon admission were enrolled. The treatment was H2A and five care modalities given during the first 24 h: restraint use, prohibited self-transfer, no oral feeding, indwelling catheters, and frequent nighttime care. The outcome was delirium within 5 days defined as Intensive Care Delirium Screening Checklist ≥4 points. We estimated the relative risk (RR) for delirium with regression models weighted by overlap weights using propensity scores estimated through logistic models incorporating known and potential confounders, including stroke severity. RESULTS: Of the 387 participants, 188 were given at least one care modality and 130 were given H2A. A total of 42 developed delirium. Delirium was significantly associated with prohibited self-transfer (RR 1.7, 95% CI 1.0-3.0), frequent nighttime care (RR 2.1, 95% CI 1.2-3.7), and multiple care modalities (RR 2.4, 95% CI 1.3-4.4), while other care modalities and H2A were not. CONCLUSIONS: This study showed possible causal effects of uncomfortable care on delirium and suggests that minimizing it could prevent delirium in acute stroke.

Development of a clinical score, PANDA, to predict delirium in stroke care unit.

BACKGROUND AND PURPOSE: Delirium frequently complicates acute stroke and worsens outcomes. Because delirium is potentially preventable, predicting its occurrence is essential. Although several prediction scores have been proposed, nurses need to quickly predict delirium in stroke care units (SCUs). We aimed to develop a simple tool for this purpose by examining a comprehensive set of potential predictors. METHODS: This is a prospective cohort study on acute stroke patients admitted to an SCU. Patients without stupor, coma, or delirium upon admission were eligible. Participants were followed for 5 days from admission. Delirium was defined as Intensive Care Delirium Screening Checklist ≥4 points. We examined 27 potential predictors, of which 13 predictors were used to developed a least absolute shrinkage and selection operator-penalized logistic regression model. Five variables with the largest coefficients were assigned one point each in the prediction score. The internal validation was performed by bootstrapping. RESULTS: Delirium occurred in 42 of the 387 participants. The score consisted of prior delirium, alcohol, NIHSS ≥5, dementia, and auditory/visual impairment (PANDA). The apparent AUC was 0.84 (95% confidence interval [CI], 0.78-0.89), and the optimism-corrected AUC was 0.81 (95% CI, 0.73-0.88). With a cutoff of ≥2 points, sensitivity was 0.78 (95% CI, 0.65-0.90), and specificity was 0.74 (95% CI, 0.70-0.79). CONCLUSIONS: PANDA score is simple and predicts delirium in an SCU satisfactorily.

Effects of stimulus conditions on vestibular evoked myogenic potentials in healthy subjects.

BACKGROUND: Characteristics of vestibular evoked myogenic potentials (VEMPs) depend on stimulus conditions. OBJECTIVE: To determine the optimal stimulus conditions for cervical and ocular VEMPs. METHODS: Participants were 23 healthy subjects. We compared air-conducted cervical and ocular VEMPs elicited by various tone-burst conditions (frequencies 500-1,000 Hz, rise/fall times 1-2 ms, and plateau times 0-6 ms) with an intensity of 105 dB normal hearing level. Effects of simultaneous contralateral masking noise on VEMPs were also evaluated. RESULTS: The largest cervical VEMP amplitudes were elicited by 500-750 Hz and 2-6 ms plateau time-tone-bursts, and the largest ocular VEMP amplitudes by 750 Hz and 2-4 ms plateau time-tone-bursts. Repeatability of the latency was better at 1 ms than at 2 ms rise/fall time in both VEMPs. In both VEMPs, masking noise reduced amplitude, and in ocular VEMP, amplitudes were significantly larger at the left ear stimulation than the right. CONCLUSION: Optimal tone-burst stimulation for both VEMPs seemed to be 500-750 Hz frequency and 1/2/1 ms rise/plateau/fall time without contralateral masking noise. Ocular VEMP amplitudes from left ear stimulation were originally larger than those from right ear stimulation.

Effects of cerebellar magnetic stimulation on chronic post-lateral medullary infarction dizziness: A proof-of-principle cohort study.

BACKGROUND AND PURPOSE: Lateral medullary infarction (LMI) sometimes causes long-lasting dizziness. Although the precise mechanism of chronic post-LMI dizziness is unknown, a cerebellar control disorder of the vestibulo-ocular reflex (VOR) has been reported in such patients. We conducted a proof-of-principle cohort study to assess the potential efficacy of cerebellar repetitive transcranial magnetic stimulation (rTMS) as treatment for chronic post-LMI dizziness. METHODS: We first applied cerebellar rTMS in healthy volunteers (n = 11) and showed that cerebellar intermittent theta burst stimulation (iTBS) affected vestibulocerebellar neural activity. Then, between September and December 2015, we enrolled six patients (aged≥20 years) with chronic post-LMI dizziness (duration≥6 months), applied cerebellar rTMS (iTBS for 5 days), and followed these patients up for up to 25 months for clinical symptoms (Dizziness Handicap Inventory [DHI]), signs (nystagmus), and VOR gain. RESULTS: Four of the six patients completed the study without complications. After rTMS, DHI scores were reduced (mean pre-rTMS DHI score minus post-rTMS DHI score was 13.0 [P = 0.036]) with disappearance of the ipsilesional nystagmus characteristic of the post-LMI dizziness. Reduction in the absolute VOR gain (mean pre- rTMS gain minus post-rTMS gain in the ipsilesional direction was 0.135 [P = 0.036] and that in the contralesional direction was 0.137 [P = 0.031]) were also associated with reduced DHI scores. Relative cerebellar blood flow to the brainstem was increased in four of five patients. The effects of cerebellar rTMS did not always persist, and three of four patients elected to undergo more than one rTMS series. The repeat cerebellar rTMS treatments had same beneficial effects. CONCLUSION: Our study showed, for the first time, the potential efficacy of cerebellar rTMS for treatment of chronic post-LMI dizziness. The short duration of the cerebellar rTMS effects can be compensated for by repeating the rTMS treatment every few months. Further large-scale randomized studies are warranted to confirm our findings.

Comparative study of ipsilesional and contralesional repetitive transcranial magnetic stimulations for acute infarction.

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) is reported to improve chronic post-stoke hemiparesis. However, application of rTMS during the acute phase of post-stroke has not fully been investigated. We investigated the safety and the efficacy of intermittent theta-burst stimulation (iTBS) of the affected motor cortex and 1-Hz stimulation of the unaffected hemisphere during the acute phase in patients with hemiparesis due to capsular infarction. METHODS: Twenty one patients who met the study criteria were randomly assigned to receive, starting within 7days after stroke onset and for a period of 10days, iTBS of the affected motor cortex hand area (n=8), 1-Hz stimulation of the unaffected motor cortex hand area (n=7), or sham stimulation (n=6). Upper limb motor function was evaluated before rTMS and 12weeks after onset of the stroke. Evaluation was based on the Fugl-Meyer Assessment (FMA), Stroke Impairment Assessment Set (SIAS), Modified Ashworth Scale (MAS), grip strength, and motor evoked potential (MEP) amplitude in the first dorsal interosseous (FDI) muscle. RESULTS: Both iTBS applied to the affected motor cortex hand area and 1-Hz stimulation applied to the unaffected motor cortex hand area enhanced motor recovery. In comparison to sham stimulation, iTBS increased the SIAS finger-function test score, and 1-Hz stimulation decreased the MAS wrist and finger score. CONCLUSIONS: Ipsilesional iTBS and contralesional 1-Hz stimulation applied during the acute phase of stroke have different effects: ipsilesional iTBS improves movement of the affected limb, whereas contralesional 1-Hz stimulation reduces spasticity of the affected limb.

[Hypoglycemic Hemiplegia].

Hypoglycemia may cause acute hemiplegia. The most common diffusion-weighted MR imaging finding in patients with hypoglycemic hemiplegia is the hyperintense lesion involving the internal capsule, mimicking acute ischemic stroke. Thus, in patients with acute onset hemiplegia, it is important to differentiate hypoglycemia on arrival by immediate blood glucose measurement. It has recently been shown that hypoglycemic brain injury start in large white matter tracts such as internal capsule and spread throughout the whole brain, including the gray matter. However, it is still unclear why focal signs such as hemiplegia develope in metabolic disorders affecting the whole brain.

[Central respiratory failure occurred in the subacute phase of unilateral Wallenberg's syndrome: a case report].

A 46-year-old man developed central respiratory failure in the subacute phase of unilateral lateral medullary infarction. He complained of sudden headache and nausea at first. Neurological examination revealed Wallenberg's syndrome. Acute right lateral medullary infarction caused by the dissecting right vertebral artery was identified by magnetic resonance images. He was transferred to our hospital on the 3rd day after the onset. He was alert and conscious on admission, and became restless gradually later. He was intubated for sudden respiratory failure on the 9th day. Blood gas analysis showed hypercapnia and hypoxia. Central respiratory failure was indicated by the fact that various examinations showed no change of his infarction, no subarachnoid hemorrhage, or no worsening of pneumonia. Ventilatory support was required for a month because of repetitive CO2 narcosis. He was weaned from the ventilator on the 39th day. Only a few reports are available on central respiratory failure associated with the subacute phase of unilateral medullary infarction. Delayed central respiratory failure may be lethal. Careful observation is required on the subacute phase of Wallenberg's syndrome.

[A case of IgM paraproteinemic neuropathy associated with anti-sulfated glucuronic paragloboside (SGPG) IgG antibody without anti-myelin-associated glycoprotein (MAG) activity].

We report a case of IgM paraproteinemic neuropathy associated with anti-sulfated glucuronic paragloboside (SGPG) IgG antibody. An 84-year old man complained of numbness on the left side of the face and in the distal portions of the limbs. Neurological examination showed mild sensory ataxia. The laboratory tests revealed the presence of IgM lambda paraproteinemia and anti-SGPG IgG antibody without anti-myelin-associated glycoprotein (MAG) activity and anti-MAG/SGPG IgM antibody. Results of nerve conduction study showed decreased sensory nerve action potential (SNAP) amplitude, indicating the presence of sensory-dominant axonal polyneuropathy, and the prolongation of distal latency was not observed. Treatment with corticosteroids resulted in a rapid improvement in neurological abnormalities. In IgM paraproteinemic neuropathy associated with anti-MAG/SGPG antibody, distal acquired demyelinating sensory neuropathy and resistance to immunological treatments are the characteristic pathologic and clinical features, respectively. On the other hand our rare case of IgM paraproteinemic neuropathy positive for anti-SGPG IgG antibody presented with axonal sensory polyneuropathy and a good responsiveness to corticosteroids.

Unilateral cone dysfunction as a manifestation of acute zonal occult outer retinopathy.

PURPOSE: To report a patient with unilateral cone dysfunction (UCD) who later developed acute zonal occult outer retinopathy (AZOOR) in the contralateral eye. METHODS: A 19-year-old Japanese woman was referred complaining of decreased vision and photopsia of the left eye. Static perimetry, full-field electroretinography (ERG), and multifocal ERGs (mfERGs) were performed to evaluate her visual functions. She returned 9 months later with visual field defect and photopsia in the right eye. RESULTS: The static visual field of the left eye demonstrated a scotoma that extended from the physiologic blind spot to the center of the visual field. The cone full-field ERGs were extinguished with preservation of rod function. The mfERGs were reduced throughout the posterior pole of the left eye. The patient was diagnosed with UCD. She revisited us 9 months later complaining of visual symptoms in the right eye and was found to have an arcuate scotoma in the upper visual field corresponding to decreased mfERGs. These findings were consistent with clinical signs of AZOOR. CONCLUSION: These findings indicate that UCD is one of the clinical manifestations of AZOOR.