Low dosages of vitamin A may cause a decrease in the total neuron number of fetal hippocampal rat cells.

OBJECTIVES: We investigated the effect of low, medium and high doses of oral vitamin A, on the number of fetal hippocampal neurons. BACKGROUND: High doses of vitamin A during pregnancy may cause embryonic malformations. There are reports about dosages that don't cause macroscopic malformations, but may cause mental and behavioral disorders. Still, quantitative morphological studies explaining this topic are lacking. METHODS: We administered oral vitamin A to pregnant rats on the 10th-12th days of pregnancy at doses of 10000, 20000, 30000, 40000, 50000, 100000 and 200000 IU/kg. We collected the fetuses on the 19th day and removed their brains. After staining with cresyl violet and immunolabeling with Tunel and Ki67 antibody, we examined the hippocampi with stereological methods. RESULTS: Vitamin A decreased hippocampal neuron numbers beginning from 20000 IU/kg. While the number of Ki67 positive cells increased with the dosage, the increase of apoptotic cells begun at the dose of 50000 IU/kg. CONCLUSION: Our study demonstrates that vitamin A, beginning from the dosage of 20000 IU/kg, is decreasing the total hippocampal neuron numbers during the critical period of embryonic brain development and that apoptosis may not be the only factor in this outcome (Tab. 1, Fig. 3, Ref. 27).

Brain imaging in patients with transient ischemic attack: a comparison of computed tomography and magnetic resonance imaging.

BACKGROUND: Brain imaging in stroke aims at the detection of the relevant ischemic tissue pathology. Cranial computed tomography (CT) is frequently used in patients with transient ischemic attack (TIA) but no data is available on how it directly compares to magnetic resonance imaging (MRI). METHODS: We compared detection of acute ischemic lesions on CT and MRI in 215 consecutive TIA patients who underwent brain imaging with either CT (n = 161) or MRI (n = 54). An MRI was performed within 24 h in all patients who had CT initially. RESULTS: An initial assessment with CT revealed no acute pathology in 154 (95.7%) and possible acute infarction in 7 (4.3%) patients. The acute infarct on CT was confirmed by diffusion-weighted imaging (DWI) in only 2 cases (28.6%). DWI detected an acute infarct in 50 of the 154 patients with normal baseline CT (32.5%). Among 54 patients without baseline CT, DWI showed acute ischemic lesions in 19 (35.2%). The ischemic lesions had a median volume of 0.87 cm(3) (range: 0.08-15.61), and the lesion pattern provided clues to the underlying etiology in 13.7%. CONCLUSION: Acute MRI is advantageous over CT to confirm the probable ischemic nature and to identify the etiology in TIA patients.

Ensemble of Convolutional Neural Networks Improves Automated Segmentation of Acute Ischemic Lesions Using Multiparametric Diffusion-Weighted MRI.

BACKGROUND AND PURPOSE: Accurate automated infarct segmentation is needed for acute ischemic stroke studies relying on infarct volumes as an imaging phenotype or biomarker that require large numbers of subjects. This study investigated whether an ensemble of convolutional neural networks trained on multiparametric DWI maps outperforms single networks trained on solo DWI parametric maps. MATERIALS AND METHODS: Convolutional neural networks were trained on combinations of DWI, ADC, and low b-value-weighted images from 116 subjects. The performances of the networks (measured by the Dice score, sensitivity, and precision) were compared with one another and with ensembles of 5 networks. To assess the generalizability of the approach, we applied the best-performing model to an independent Evaluation Cohort of 151 subjects. Agreement between manual and automated segmentations for identifying patients with large lesion volumes was calculated across multiple thresholds (21, 31, 51, and 70 cm3). RESULTS: An ensemble of convolutional neural networks trained on DWI, ADC, and low b-value-weighted images produced the most accurate acute infarct segmentation over individual networks (P < .001). Automated volumes correlated with manually measured volumes (Spearman ρ = 0.91, P < .001) for the independent cohort. For the task of identifying patients with large lesion volumes, agreement between manual outlines and automated outlines was high (Cohen κ, 0.86-0.90; P < .001). CONCLUSIONS: Acute infarcts are more accurately segmented using ensembles of convolutional neural networks trained with multiparametric maps than by using a single model trained with a solo map. Automated lesion segmentation has high agreement with manual techniques for identifying patients with large lesion volumes.

Predictors for limb loss among patient with diabetic foot infections: an observational retrospective multicentric study in Turkey.

We aimed to investigate the predictors for limb loss among patients with diabetes who have complicated skin/soft-tissue infections. In this observational study, consecutive patients with diabetic foot infection (DFI) from 17 centres in Turkey, between May 2011 and May 2013 were included. The Turkish DFI Working Group performed the study. Predictors of limb loss were investigated by multivariate analysis. In total, 455 patients with DFI were included. Median age was 61 years, 68% were male, 65% of the patients were hospitalized, 52% of the patients had used antibiotics within the last month, and 121 (27%) had osteomyelitis. Of the 208 microorganisms isolated, 92 (44.2%) were Gram-positive cocci and 114 (54.8%) were Gram-negative rods (GNR). The most common GNR was Pseudomonas; the second was Escherichia coli, with extended spectrum ß-lactamase positivity of 33%. Methicillin-resistant Staphylococcus species were found in 14% (29/208). Amputations were performed in 126/455 (28%) patients, 44/126 (34%) of these were major amputations. In multivariate analysis, significant predictors for limb loss were, male gender (OR 1.75, 95% CI 1.04-2.96, p 0.034), duration of diabetes >20 years (OR 1.9, 95% CI 1.18-3.11, p 0.008), infected ulcer versus cellulitis (OR 1.9, 95% CI 1.11-3.18, p 0.019), history of peripheral vascular disease (OR 2, 95% CI 1.26-3.27, p 0.004), retinopathy (OR 2.25, 95% CI 1.19-4.25, p 0.012), erythrocyte sedimentation rate >70 mm/hr (OR 1.6, 95% CI 1.01-2.68, p 0.05), and infection with GNR (OR 1.8, 95% CI 1.08-3.02, p 0.02). Multivariate analysis revealed that, besides the known risk factors such as male gender, duration of diabetes >20 years, infected ulcers, history of peripheral vascular disease and retinopathy, detection of GNR was a significant predictor of limb loss.

Diffusion-weighted magnetic resonance imaging identifies the "clinically relevant" small-penetrator infarcts.

BACKGROUND: Most patients initially seen with a clinical syndrome consistent with a small-penetrator infarct (SPI) also harbor multiple, chronic, hyperintense, white matter lesions on conventional magentic resonance imaging (ie, T2-weighted image [T2WI] and fluid-attenuation inversion recovery [FLAIR] imaging). Diffusion-weighted imaging (DWI) can identify the clinically relevant "index infarction" in such circumstances, since it differentiates between acute and chronic lesions. OBJECTIVE: To determine the clinical and radiological predictors associated with misidentification of an SPI as acute using T2WI and FLAIR images in patients with an acute SPI seen on DWI. PATIENTS: Sixty-seven consecutive patients who had an SPI. METHODS: Two independent examiners, provided with brief clinical information, but blinded to DWI findings, sought a clinically appropriate lesion on T2WI and FLAIR imaging in 67 consecutive patients found to have an SPI seen on DWI. RESULTS: The index infarction based on evaluation of T2WI or FLAIR images was in a different location than the acute lesion as identified by DWI in 9 (13%) and 11 (16%) of 67 patients, respectively. Both T2WI and FLAIR imaging were rated normal in another 9% of the patients. Multivariate analysis showed that small lesion size (<10 mm) was the only predictor of misidentifying the clinically appropriate lesion on conventional magnetic resonance imaging (P<.01). CONCLUSIONS: T2-weighted imaging and FLAIR imaging fail to identify the clinically relevant SPI in almost one quarter of the patients found to have a lesion on DWI. The characteristics of DWI make it well suited for the detection of acute small infarcts. Diffusion-weighted imaging is necessary to consistently define the clinical-anatomical relations in patients initially seen with SPIs.

Diffusion-weighted MRI characterizes the ischemic lesion in transient global amnesia.

We present a patient with transient global amnesia (TGA) whose diffusion-weighted MRI (DWI) showed increased signal in the splenium of the corpus callosum and in the left parahippocampal gyrus. The absence of high signal on the corresponding apparent diffusion coefficient (ADC) images supports the diagnosis of an acute infarction. This finding provides a temporal relation between cerebral ischemia and infarction in the territory of posterior cerebral artery and in certain cases of TGA. An early means of detecting ischemia in TGA by DWI may influence clinical decisions made in patient evaluation and management.

Posterior leukoencephalopathy without severe hypertension: utility of diffusion-weighted MRI.

OBJECTIVE: Standard MRI confirms the diagnosis of posterior leukoencephalopathy syndrome (PLES), recently associated with an increasing number of medical conditions. In PLES, T2-weighted MRI demonstrates hyperintensity spreading out from posterior brain regions; the pathophysiology remains mysterious. In the acute setting, diffusion-weighted imaging (DWI), but not standard MR imaging, can distinguish ischemic injury from those conditions known to cause vasogenic brain edema. DWI is potentially valuable in understanding the pathophysiology of PLES and in diagnosing patients who do not have previously known risk factors. METHODS: Serial CT and MRI studies (including DWI, apparent diffusion coefficient [ADC] maps, and, in one instance, perfusion-weighted imaging) were performed in three female patients with a neurologic syndrome consistent with PLES while hospitalized for treatment of other conditions. RESULTS: None of the patients had previously described risk factors for PLES; all had only mild elevations in blood pressure. MRI showed large, abnormal, T2 hyperintense regions in the posterior cerebrum with corresponding hyperintensity on ADC maps-signal characteristics predominantly consistent with vasogenic edema. There were also smaller patchy posterior cortical regions with decreased ADC and bright DWI consistent with infarction in one, and dramatic conversion of a large region to an ischemic pattern in another. CONCLUSIONS: ADC maps and DWI can successfully differentiate PLES from early cerebral ischemia, thus playing a pivotal role in treatment decisions. PLES is associated with a wider variety of conditions than has been previously reported and is not always reversible. Hyperintense DWI signal in patients with the syndrome likely marks a tissue stage of permanent brain injury.

Normal diffusion-weighted MRI during stroke-like deficits.

BACKGROUND: Diffusion-weighted MRI (DWI) represents a major advance in the early diagnosis of acute ischemic stroke. When abnormal in patients with stroke-like deficit, DWI usually establishes the presence and location of ischemic brain injury. However, this is not always the case. OBJECTIVE: To investigate patients with stroke-like deficits occurring without DWI abnormalities in brain regions clinically suspected to be responsible. METHODS: We identified 27 of 782 consecutive patients scanned when stroke-like neurologic deficits were still present and who had normal DWI in the brain region(s) clinically implicated. Based on all the clinical and radiologic data, we attempted to arrive at a pathophysiologic diagnosis in each. RESULTS: Best final diagnosis was a stroke mimic in 37% and a cerebral ischemic event in 63%. Stroke mimics (10 patients) included migraine, seizures, functional disorder, transient global amnesia, and brain tumor. The remaining patients were considered to have had cerebral ischemic events: lacunar syndrome (7 patients; 3 with infarcts demonstrated subsequently) and hemispheric cortical syndrome (10 patients; 5 with TIA, 2 with prolonged reversible deficits, 3 with infarction on follow-up imaging). In each of the latter three patients, the regions destined to infarct showed decreased perfusion on the initial hemodynamically weighted MRI (HWI). CONCLUSIONS: Normal DWI in patients with stroke-like deficits should stimulate a search for nonischemic cause of symptoms. However, more than one-half of such patients have an ischemic cause as the best clinical diagnosis. Small brainstem lacunar infarctions may escape detection. Concomitant HWI can identify some patients with brain ischemia that is symptomatic but not yet to the stage of causing DWI abnormality.

Localization of clinical syndromes using DWI: two examples of the "capsular" warning syndrome.

The capsular warning syndrome (CWS) is a subtype of transient ischemic attack characterized by its recurrent nature, absence of cortical signs, and high probability of early capsular stroke. Currently, standard imaging techniques have identified only internal capsule lesions in this entity. The authors present 2 cases with an otherwise typical CWS in whom a brainstem stroke was detected by diffusion-weighted imaging (DWI). DWI's ability to differentiate between acute and chronic infarcts may assist in more accurate localization of clinical syndromes.

Rubral tremor after thalamic infarction in childhood.

The occurrence of tremor after thalamic lesions is well known. Delayed rubral tremor secondary to bilateral thalamic infarction is a rare finding and has not been reported previously in childhood. We present two children with a combined resting-postural-kinetic tremor caused by bithalamic infarction. The first child was a male 14 months of age, and the second was a male 9 years of age. These children come from unrelated families. On hospital admission of the first patient, generalized seizures and routine electroencephalogram (EEG) findings with diffuse spike-wave discharges predominantly over the left frontal area were clinically observed, leading to the initial diagnosis of epilepsia partialis continua. However, clinical observation and video-EEG monitoring of the movements revealed nonepileptiform accompaniments, favoring the diagnosis of rubral tremor. In the second patient, EEG revealed no paroxysmal activity and was within normal limits for age. In both patients, cranial magnetic resonance imaging revealed ischemic lesions in thalami bilaterally but failed to reveal any mesencephalic lesion. These patients demonstrate that thalamic infarction can cause rubral tremor in childhood.