The Role of Novel Imaging and Biofluid Biomarkers in Traumatic Axonal Injury: An Updated Review.

Traumatic brain injury (TBI) is a leading cause of disability worldwide. Traumatic axonal injury (TAI) is a subtype of TBI resulting from high-impact forces that cause shearing and/or stretching of the axonal fibers in white matter tracts. It is present in almost half of cases of severe TBI and frequently associated with poor functional outcomes. Axonal injury results from axonotomy due to mechanical forces and the activation of a biochemical cascade that induces the activation of proteases. It occurs at a cellular level; hence, conventional imaging modalities often fail to display TAI lesions. However, the advent of novel imaging modalities, such as functional magnetic resonance imaging and fiber tractography, has significantly improved the detection and characteristics of TAI. Furthermore, the significance of several fluid and structural biomarkers has also been researched, while the contribution of omics in the detection of novel biomarkers is currently under investigation. In the present review, we discuss the role of imaging modalities and potential biomarkers in diagnosing, classifying, and predicting the outcome in patients with TAI.

Functional connectivity and microstructural changes of the brain in primary Sjögren syndrome: the relationship with depression.

BACKGROUND: Fatigue and depression are among the most common manifestations of primary Sjögren syndrome (pSS), but information is lacking on the relationship with brain function and microstructural changes. PURPOSE: To investigate microstructural changes and brain connectivity in pSS, and to evaluate their relationship with fatigue and depression. MATERIAL AND METHODS: The study included 29 patients with pSS (mean age 61.2 ± 12.1 years; disease duration 10.5 ± 5.9 years) and 28 controls (mean age 58.4 ± 9.2 years). All the patients completed the Beck's depression and Fatigue Assessment Scale questionnaires. The imaging protocol consisted of: (i) standard magnetic resonance imaging (MRI) pulse sequences (FLAIR, 3D T1W); (ii) a diffusion tensor imaging pulse sequence; and (iii) a resting state functional MRI pulse sequence. Resting state brain networks and maps of diffusion metrics were calculated and compared between patients and controls. RESULTS: Compared with the controls, the patients with pSS and depression showed increased axial, radial, and mean diffusivity and decreased fractional anisotropy; those without depression showed decreased axial diffusivity in major white matter tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus, corticospinal tract, anterior thalamic radiation, inferior fronto-occipital fasciculus, cingulum, uncinate fasciculus, and forceps minor-major). Decreased brain activation in the sensorimotor network was observed in the patients with pSS compared with the controls. No correlation was found between fatigue and structural or functional changes of the brain. CONCLUSION: pSS is associated with functional connectivity abnormalities of the somatosensory cortex and microstructural abnormalities in major white matter tracts, which are more pronounced in depression.

Postpartum intracranial hypotension complicated by posterior reversible encephalopathy syndrome: a case report.

Purpose: To present an unusual case of posterior encephalopathy syndrome (PRES) preceded by intracranial hypotension.Materials and Methods: We present a case of a 27-year-old parturient with an uneventful pregnancy that shortly after labor developed a persistent headache with characteristics compatible with intracranial hypotension. The patient had undergone epidural anesthesia for caesarian section. Results: The symptomatology of intracranial hypotension was attributed to inadvertent dural puncture during epidural anesthesia. The MRI revealed multiple white matter lesions located in frontal, temporal and parietal regions of both hemispheres. The type of lesions was suggestive of PRES. Pachymeningeal enhancement was also observed. The patient was managed conservatively. The symptoms improved gradually and the imaging findings resolved completely. Conclusions: This case demonstrates the need for clinical alertness for PRES in patients with prolonged and possibly atypical symptoms of intracranial hypotension. As probable causal relationship between these disorders we propose a sympathetic over-activation as a result of cerebrospinal fluid leakage leading to vasospasm and manifestation of PRES.

Functional and structural connectivity of the brain in very preterm babies: relationship with gestational age and body and brain growth.

BACKGROUND: Structural and functional changes of the brain have been reported in premature babies. OBJECTIVE: To evaluate the relationship of functional and structural connectivity with gestational age, body growth and brain maturation in very preterm babies. MATERIALS AND METHODS: We studied 18 very preterm babies (gestational age: mean ± standard deviation, 29.7±1.7 weeks). We examined functional connectivity by multivariate pattern analysis of resting-state functional MRI data. We assessed structural connectivity by analysis of diffusion tensor imaging data and probabilistic tractography. RESULTS: The average functional connectivity of the medial orbitofrontal cortex with the rest of the brain was positively associated with gestational age (P<0.001). Fractional anisotropy of the right inferior fronto-occipital fasciculus was positively associated with head circumference at term-equivalent age. Structural connectivity of the inferior fronto-occipital fasciculus with the medial orbitofrontal cortex was positively associated with head circumference at term-equivalent age. Body weight at term-equivalent age was the only independent predictor of average structural connectivity of the medial orbitofrontal cortex with the rest of the brain (P=0.020). CONCLUSION: Structural and functional connectivity of the medial orbitofrontal cortex with the rest of the brain depend on body growth and degree of prematurity, respectively.

Multifocal alterations of white matter accompany the transition from normal cognition to dementia in Parkinson's disease patients.

The purpose of the present study was to investigate the pattern of white matter (WM) changes associated with Parkinson's disease (PD)-related cognitive impairment by using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) measures. Diffusion Tensor Imaging (DTI) was performed in 21 PD-patients with dementia (PDD) and in an age-matched control group including 40 PD-patients without dementia (PD-CTRL). The Parkinson's disease-Cognitive Rating Scale (PD-CRS) was used for patients' neuropsychological assessment. Local microstructural WM differences associated with the presence of cognitive impairment were tested using tract-based spatial statistics analysis. Multiple regression models investigated the association of DTI indices with total PD-CRS score, PD-CRS raw items and other clinical measures across the whole study sample. Significant FA decreases were found in PDD compared to PD-CTRL patients mainly in the body of corpus callosum, corona radiata and cingulum. Lower PD-CRS score was significantly associated with decreased FA, MD and AD values in multiple WM tracts primarily located in prefrontal and limbic areas as well as across the corpus callosum. Lower performance in specific PD-CRS raw items was also associated with FA decreases in major WM tracts. The results suggest that multifocal microstructural changes of WM accompany the transition from normal to demented cognitive state in PD-patients. The corpus callosum, the corona radiata and the cingulum are among the regions mostly affected during this course. A progressive axonal degeneration is proposed as a key underlying mechanism.

Pseudoexfoliation syndrome without glaucoma: White matter abnormalities detected by conventional MRI and diffusion tensor imaging.

PURPOSE: To assess macro- and microstructural brain changes in patients with pseudoexfoliation syndrome (PXS). MATERIALS AND METHODS: Comprehensive ophthalmic examination and brain MRI were conducted on 20 patients with PXS without glaucoma (aged 62.75 ±â€¯0.4 years) and 20 controls (aged 62 ±â€¯0.6 years). White matter (WM) integrity was evaluated on FLAIR and single-shot multisection SE-EPI diffusion tensor imaging (DTI) sequences. The presence and the number of white matter hyperintensities (WMHIs) on FLAIR images was compared between all patients and control subjects. Microstructural WM changes on DTI was evaluated using Tract-based spatial statistics (TBSS). DTI metrics of the optic tracts were assessed by the region-of-interest (ROI) method. RESULTS: A significantly higher number of WMHIs was found in the patients with PXS than in the control subjects (P ≤ 0.002). On DTI the patients showed bilateral increase in the mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) values in the anterior thalamic radiation, the inferior fronto-occipital fasciculus, the superior longitudinal fasciculus, the inferior longitudinal fasciculus and the forceps minor. TBSS revealed no significant difference in fractional anisotropy (FA) values, but ROIs analysis of the optic tracts revealed decreased FA values in the patients. CONCLUSION: MRI in patients with PXS detects abnormalities in the brain and the optic tracts at a subclinical stage. Early detection of microstructural changes could be useful to guide appropriate treatment to impede the disease process.

Mitochondrial Membrane Dynamics and Inherited Optic Neuropathies.

Inherited optic neuropathies are a genetically diverse group of disorders mainly characterized by visual loss and optic atrophy. Since the first recognition of Leber's hereditary optic neuropathy, several genetic defects altering primary mitochondrial respiration have been proposed to contribute to the development of syndromic and non-syndromic optic neuropathies. Moreover, the genomics and imaging revolution in the past decade has increased diagnostic efficiency and accuracy, allowing recognition of a link between mitochondrial dynamics machinery and a broad range of inherited neurodegenerative diseases involving the optic nerve. Mutations of novel genes modifying mainly the balance between mitochondrial fusion and fission have been shown to lead to overlapping clinical phenotypes ranging from isolated optic atrophy to severe, sometimes lethal multisystem disorders, and are reviewed herein. Given the particular vulnerability of retinal ganglion cells to mitochondrial dysfunction, the accessibility of the eye as a part of the central nervous system and improvements in technical imaging concerning assessment of the retinal nerve fiber layer, optic nerve evaluation becomes critical - even in asymptomatic patients - for correct diagnosis, understanding and early treatment of these complex and enigmatic clinical entities.

The association between multiple sclerosis and spondylosis: When and why.

OBJECTIVES: To evaluate risk factors for the development of cervical spine spondylosis (CSS) in patients with multiple sclerosis (MS) and to propose a pathogenetic mechanism. METHODS: Forty-two consecutive patients aged 23-66 years with MS and 42 age and sex matched controls were evaluated retrospectively; Clinical disability was evaluated with the expanded disability status scale (EDSS) and spasticity with the Asworth score. Total brain lesion volume (BLV), total grey matter (GM) volume and deep GM volume were assessed. In the cervical spine CSS indices (disk dehydration, disk protrusion, abnormal posture and osteophytosis) and the spinal cord lesion load (SLL) was evaluated. The association of CSS indices with the presence of MS, the clinical scales and the brain and spinal cord imaging measurements were assessed. RESULTS: Presence of MS was positively associated with abnormal posture (P=0.002), disk dehydration at C6-C7 (P=0.049) and posterior disk protrusion at C5-C6 (P=0.033) and C6-C7 (P=0.001). All patients had spasticity. Patients with abnormal posture were younger (37.5±11.1years) than those with normal (45.4±8.6years), P=0.024. Age (P=0.008), EDSS (P=0.045) and BLV (P=0.084) were significant independent predictors of abnormal posture. Younger age combined with worse EDSS and increased BLV predicted abnormal posture. CONCLUSIONS: Patients with MS present more frequently spondylosis which is associated with younger age, more severe disability and extensive lesions in the brain. Spasticity induced by the brain lesions and abnormal expression of extracellular matrix proteins in the brain and the intervertebral disk constitute a possible pathogenetic mechanism.

Abnormalities of brain neural circuits related to obesity: A Diffusion Tensor Imaging study.

PURPOSE: Increased Body-Mass-Index (BMI) has been associated with brain atrophy in both gray and white matter structures. However, little is known concerning the integrity of white matter tracts in obesity. The purpose of the study was to evaluate the pattern of changes in white matter microstructure in human adiposity. MATERIAL AND METHODS: The study included 268 participants (52 obese, 96 overweight and 120 normal-weight) that were retrospectively evaluated by Diffusion Tensor Imaging. The fractional anisotropy, axial, radial and mean diffusivity values were compared between the above groups using Tract Based Spatial Statistics. RESULTS: The analysis revealed that the increased BMI was related with decreased fractional anisotropy in several white matter regions including the anterior and posterior thalamic radiation, the inferior fronto-occipital fasciculus, the inferior and superior longitudinal fasciculus, the corpus callosum (callosal body and forceps minor), the uncinate fasciculus, the internal capsule, the corticospinal tract and the cingulum (cingulate gyrus and hippocampus). CONCLUSIONS: Anisotropic diffusion of anatomic regions governing important brain circuits such as reward seeking inhibition, motivation/drive and learning/conditioning decreases with increasing BMI.

Diffusion tensor imaging in children with tuberous sclerosis complex: tract-based spatial statistics assessment of brain microstructural changes.

BACKGROUND: There is evidence of microstructural changes in normal-appearing white matter of patients with tuberous sclerosis complex. OBJECTIVE: To evaluate major white matter tracts in children with tuberous sclerosis complex using tract-based spatial statistics diffusion tensor imaging (DTI) analysis. MATERIALS AND METHODS: Eight children (mean age ± standard deviation: 8.5 ± 5.5 years) with an established diagnosis of tuberous sclerosis complex and 8 age-matched controls were studied. The imaging protocol consisted of T1-weighted high-resolution 3-D spoiled gradient-echo sequence and a spin-echo, echo-planar diffusion-weighted sequence. Differences in the diffusion indices were evaluated using tract-based spatial statistics. RESULTS: Tract-based spatial statistics showed increased axial diffusivity in the children with tuberous sclerosis complex in the superior and anterior corona radiata, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the uncinate fascicle and the anterior thalamic radiation. No significant differences were observed in fractional anisotropy, mean diffusivity and radial diffusivity between patients and control subjects. No difference was found in the diffusion indices between the baseline and follow-up examination in the patient group. CONCLUSION: Patients with tuberous sclerosis complex have increased axial diffusivity in major white matter tracts, probably related to reduced axonal integrity.

Multimodal imaging evaluation of excessive daytime sleepiness in Parkinson's disease.

PURPOSE OF THE STUDY: The multimodal imaging investigation of excessive daytime sleepiness (EDS) in Parkinson's disease (PD). The role of dopaminergic treatment and other clinical parameters was also evaluated. MATERIALS AND METHODS: Seventeen non-demented PD patients with EDS (PD-EDS) and 17 PD patients without EDS were enrolled. Clinical, treatment and MRI data were acquired. Gray matter (GM) volume was examined with voxel-based morphometry, while white matter (WM) integrity was assessed with diffusion tensor imaging by means of fractional anisotropy, mean diffusivity, axial diffusivity (AD) and radial diffusivity measures. RESULTS: Increased regional GM volume was found in the PD-EDS group bilaterally in the hippocampus and parahippocampal gyri. Increased AD values were also shown in the PD-EDS group, in the left anterior thalamic radiation and the corticospinal tract and bilaterally in the superior corona radiata and the superior longitudinal fasciculus. Levodopa equivalent dose differed significantly between the groups and was the only predictor of EDS, while the only predictor of the Epworth sleepiness scale score in the PD-EDS group was the dopamine-agonist dose. Increased frequency of gamblers was also observed in the PD-EDS group. CONCLUSIONS: Regional GM increases and increased AD values in certain WM tracts were found in the PD-EDS group. The changes could result from disinhibited signaling pathways or represent compensatory changes in response to anatomical or functional deficits elsewhere. The study findings support also the contribution of the total dopaminergic load in the development of EDS, while the dose of dopamine agonists was found to predict the severity of the disorder.

Brain involvement in patients with inflammatory bowel disease: a voxel-based morphometry and diffusion tensor imaging study.

OBJECTIVES: To investigate structural brain changes in inflammatory bowel disease (IBD). METHODS: Brain magnetic resonance imaging (MRI) was performed on 18 IBD patients (aged 45.16 ± 14.71 years) and 20 aged-matched control subjects. The imaging protocol consisted of a sagittal-FLAIR, a T1-weighted high-resolution three-dimensional spoiled gradient-echo sequence, and a multisession spin-echo echo-planar diffusion-weighted sequence. Differences between patients and controls in brain volume and diffusion indices were evaluated using the voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) methods, respectively. The presence of white-matter hyperintensities (WMHIs) was evaluated on FLAIR images. RESULTS: VBM revealed decreased grey matter (GM) volume in patients in the fusiform and the inferior temporal gyrus bilaterally, the right precentral gyrus, the right supplementary motor area, the right middle frontal gyrus and the left superior parietal gyrus (p < 0.05). TBSS showed decreased axial diffusivity (AD) in the right corticospinal tract and the right superior longitudinal fasciculus in patients compared with controls. A larger number of WMHIs was observed in patients (p < 0.05). CONCLUSIONS: Patients with IBD show an increase in WMHIs and GM atrophy, probably related to cerebral vasculitis and ischaemia. Decreased AD in major white matter tracts could be a secondary phenomenon, representing Wallerian degeneration. KEY POINTS: • There is evidence of central nervous system involvement in IBD. • Diffusion tensor imaging detects microstructural brain abnormalities in IBD. • Voxel based morphometry reveals brain atrophy in IBD.

Neurological adverse events in patients receiving anti-TNF therapy: a prospective imaging and electrophysiological study.

INTRODUCTION: The aim was to investigate the frequency of neurological adverse events in patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA) treated with tumor necrosis factor (TNF) α antagonists. METHODS: Seventy-seven patients eligible for anti-TNFα therapy were evaluated. There were 36 patients with RA, 41 with SpA [24 psoriatic arthritis (PsA) and 17 with ankylosing spondylitis (AS)]. All patients had a complete physical and neurological examination. Brain and cervical spine magnetic resonance imaging (MRI) and neurophysiological tests were performed in all patients before the initiation of anti-TNFα therapy and after a mean of 18 months or when clinical symptoms and signs indicated a neurological disease. Exclusion criteria included hypertension, diabetes mellitus, dyslipidemia, heart arrhythmias, atherothrombotic events, vitamin B12 and iron deficiency, head and neck trauma and neurological surgeries. RESULTS: Two patients did not receive anti-TNFα therapy because brain MRIs at baseline revealed lesions compatible with demyelinating diseases. Thus, 75 patients received anti-TNFα (38 infliximab, 19 adalimumab and 18 etanercept). Three patients developed neurological adverse events. A 35-year-old man with PsA after 8 months of infliximab therapy presented with paresis of the left facial nerve and brain MRI showed demyelinating lesions. Infliximab was discontinued and he was treated with pulses of corticosteroids recovering completely after two months. The second patient was a 45-year-old woman with RA who after 6 months of adalimumab therapy presented with optic neuritis. The third patient was a 50-year-old woman with AS, whom after 25 months of infliximab therapy, presented with tingling and numbness of the lower extremities and neurophysiological tests revealed peripheral neuropathy. In both patients anti-TNF were discontinued and they improved without treatment after 2 months. The rest of our patients showed no symptoms and MRIs showed no abnormalities. The estimated rate of neurological adverse events in patients treated with anti-TNF therapy is 4% (3/75). CONCLUSIONS: Neurological adverse events after anti-TNFα therapy were observed in our patient. Brain MRI and neurophysiological tests are essential tools to discriminate neurological diseases.

Cardiovascular risk profile in patients with spondyloarthritis.

OBJECTIVES: The spondyloarthritides (SpA) are associated with an increased cardiovascular risk. We studied cardiovascular risk factors in patients with SpA. METHODS: The following risk factors were assessed in SpA patients and healthy controls: smoking, family history of premature ischemic heart disease, obesity, serum lipids, apolipoproteins, urate and carotid intima media thickness (IMT). RESULTS: Overall 150 patients (73 with ankylosing spondylitis [AS], 71 with psoriatic arthritis [PsA] and six with other SpA types) were included. Generally SpA patients were significantly more often smokers, while PsA patients had greater values of abdominal obesity. AS patients had significantly lower levels of triglyceride, HDL, ApoB, ApoE and Lp(a) and a higher atherogenic index (total cholesterol/HDL). PsA patients had significantly lower levels of HDL, ApoAI and ApoE, an elevated atherogenic index and higher serum urate. In multivariate analysis the atherogenic index was positively associated with SpA across all patient groups independently of smoking and other lipid parameters. Carotid IMT in SpA patients (0.71 mm) was higher than controls (0.63 mm, P=0.017), although after adjusting for smoking this ceased to be significant. Treatment of patients with previously untreated disease resulted in a small but significant decline in ApoB levels at 6 months (P=0.045), which, however, was no longer evident at 12 months. CONCLUSION: Spondyloarthritis patients are at a greater cardiovascular risk owing to the higher prevalence of smoking and a higher atherogenic index. PsA patients have more abdominal fat and higher urate levels. Immunosuppressive treatment of SpA produces minor and temporary effects on the lipid profile.

Diffusion tensor and dynamic susceptibility contrast MRI in glioblastoma.

OBJECTIVE: We prospectively investigated the correlation between diffusion tensor (DTI), dynamic susceptibility contrast (DSC) perfusion MRI metrics and Ki-67 labelling index in glioblastomas. METHODS: We studied seventeen patients who were operated on for glioblastoma. DTI and DSC MRI were performed within a week prior to surgical excision. Lesion/normal ratios were calculated for the apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and relative mean transit time (rMTT) ratio. In the excised tumour specimens Ki-67 antigen expression was evaluated by the MIB-1 immunostaining method. RESULTS: A significant correlation was observed between Ki-67 index and ADC ratio (r = -0.528, p = 0.029) and FA ratio (r = 0.589, p = 0.012). rCBV and rMTT presented a trend towards significant correlation with Ki-67 index (r = 0.628, p = 0.07 and r = 0.644, p = 0.06 respectively). There was a trend towards better survival for patients with gross total tumour excision and FA values lower than 0.48 (p = 0.1 and p = 0.09 respectively). No significant correlation was found between ADC ratio, rCBV, rCBF, rMTT and overall survival. CONCLUSION: ADC ratio, FA ratio, rCBV and rMTT tumour/normal tissue ratios may represent indicators of glioma proliferation. FA values may hold promise for predicting survival in patients with glioblastoma.

The usefulness of magnetic resonance imaging of the hand and wrist in very early rheumatoid arthritis.

INTRODUCTION: Magnetic resonance imaging (MRI) was used to study the hand and wrist in very early rheumatoid arthritis (RA), and the results were compared with early and established disease. METHODS: Fifty-seven patients fulfilling the new American College of Rheumatology criteria for RA, 26 with very early RA (VERA), 18 with early RA (ERA), and 13 with established RA (ESTRA), (disease duration < 3 months, < 12 months, and > 12 months, respectively) were enrolled in the study. MRI of the dominant hand and wrist was performed by using fat-suppressed T2-weighted and plain and contrast-enhanced T1-weighted sequences. Evaluation of bone marrow edema, synovitis, and bone erosions was performed with the OMERACT RA MRI scoring system. RESULTS: Edema, erosions, and synovitis were present in VERA, and the prevalence was 100%, 96.15%, and 92.3%, respectively. Significant differences in edema and erosions were found between VERA and ESTRA (P < 0.05). No significant difference was found in synovitis. CONCLUSIONS: Edema, erosions, and synovitis are findings of very early RA. MRI, by detecting these lesions, may play an important role in the management of these patients.

Cerebral venous thrombosis in an adolescent with ulcerative colitis.

We describe a 17-year-old Caucasian adolescent with ulcerative colitis who presented with cerebral venous sinus thrombosis. Laboratory investigation revealed low protein S levels. With successful management the patient remained without neurologic sequalae. Although there may be an association between ulcerative colitis and cerebral venous sinus thrombosis, the exact pathophysiologic mechanism remains unknown.

Periocular xanthogranuloma: A forgotten entity?

Periocular xanthogranulomatous diseases are a rare group of disorders which are characterized by a predilection to affect the orbit and ocular adnexa and special histopathological features, in particular infiltrates comprising non-Langerhans-derived foamy histiocytes and Touton giant cells. The differential diagnosis is difficult and occasionally definite diagnosis cannot be established even after clinical and histopathological findings are taken together. We describe a case of a middle-aged man who presented with a 10-year history of voluminous eyelid swelling with concomitant late-onset atopic manifestations, namely bronchial asthma and allergic rhinitis with nasal polyps. After thorough clinical and laboratory investigation, including a biopsy of the eyelid, we classified the patient's disease to a rare entity that has been relatively recently described: periocular xanthogranuloma associated with adult-onset asthma. In a review of the literature, no prospective trials concerning the treatment of this disease were found. The literature mainly contained case reports and case series in which corticosteroids and chemotherapy with alkylating agents have been reported to be beneficial. We treated our patient with a combination of oral corticosteroids and cyclophosphamide pulses and we observed substantial regression of the eyelid masses together with a normalization of systemic immunologic abnormalities.

Acute Haemophilus parainfluenzae endocarditis: a case report.

INTRODUCTION: Numerous pathogens can cause infective endocarditis, including Haemophilus parainfluenzae. H. parainfluenzae is part of the H. aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae group that may cause about 3% of the total endocarditis cases, and is characterized by a subacute course and large vegetations. CASE PRESENTATION: Acute H. parainfluenzae endocarditis developed in a 54-year-old woman, with no underlying predisposing factors. The patient presented with fever of 3 days duration and a severe headache. Magnetic resonance imaging of the brain revealed multiple cerebral emboli with hemorrhagic foci. Upon suspicion of endocarditis, cardiac transesophageal ultrasonography was performed and revealed massive vegetations. The patient underwent emergency mitral valve replacement, and was further treated with ceftriaxone. Blood cultures grew H. parainfluenzae only after valve replacement, and a 6-week course of ceftriaxone was prescribed. CONCLUSION: We underline the typical presentation of large vegetations in H. parainfluenzae endocarditis, which are associated with embolic phenomena and resulting severity. Although the majority of the few cases reported in the literature are subacute in progress, our case further underlines the possibility that H. parainfluenzae endocarditis may develop rapidly. Thus, awareness of the imaging characteristics of the pathogen may enhance early appropriate diagnosis and therapeutic response.