Investigating the Effects of Level-Specific CE-Chirp on Auditory Brainstem Response Waves in Normal Hearing Infants.

Background: Auditory brainstem response (ABR) to the level-specific (LS) CE-Chirp has been reported to provide optimum neural synchrony along cochlear partitions, theoretically improving ABR waveform resolution. Despite this promising finding, limited studies have been conducted to contrast the results between LS CE-Chirp and Click stimuli. The current study aimed to compare the results of ABR between the two stimuli (Click and LS CE-Chirp). Method: Sixty-seven normal-hearing infants, both with and without risk factors, aged less than 7 months old, participated in this study. The ABR test was conducted at 70 dBnHL using 33.3 stimulus repetition rates with both Click and LS CE-Chirp stimuli. The signal averaging was stopped at a maximum fixed signal average of 2,500 sweeps. Data were statistically compared between the two stimuli using the Wilcoxon signed-rank test. Results: The waves I and V ABRs elicited by LS CE-Chirp exhibited significantly larger amplitudes than the Click stimulus. However, the amplitude of wave III and absolute latencies were similar in both stimuli at a supra-threshold level. Conclusion: LS CE-Chirp has the advantage of larger amplitudes than the ABR from Click at the supra-threshold level (70 dBnHL) in normal-hearing infants.

The Relationship between Speech Sound Disorder and Cortical Auditory Evoked Potential.

INTRODUCTION: Speech sound disorder (SSD) is a speech and language disorder associated with difficulties in motor production, perception, and phonological representation of sounds and speech segments. Since auditory perception has a fundamental role in forming and organizing sound representation for its recognition, studies that evaluate the cortical processing of sounds are required. Thus, the present study aimed to verify the relation between SSD severity measured by the percentage of correct consonants (PCCs) with the cortical auditory evoked potentials (CAEPs) using speech stimulus. METHODS: Twenty-nine children with normal hearing participated in this research and were grouped into three groups by SSD level measured by the PCC index. In addition, the groups were subdivided according to the children's age group: between 60-71 months, 72-83 months, and 83-94 months. The CAEP with speech stimulus was carried out in all children. RESULTS: Older children had longer P1 and N1 latencies. In P2 latency, there was an interference of age only in the severe group. The N2 latency was affected by age, where older children had longer latency. CONCLUSION: The amplitude of CAEP has not suffered any interference with the age, or severity of SSD. For the latency, older children generally presented longer averages than younger ones.

Acute peripheral facial paralysis caused by tegmental pontine infarction.

Facial paralysis presents as unilateral mouth drooping and lagophthalmos. The main causes of peripheral facial paralysis are Bell's palsy and Ramsay-Hunt syndrome. However, rarely occurring pontine infarctions of the facial nucleus also manifest a lower motor neuron pattern of facial paralysis. We report a case of a man in his 50s who presented to the emergency department with unilateral peripheral facial paralysis. The initial diffusion-weighted images were unremarkable, and the patient was managed as per guidelines for hypertensive encephalopathy or Bell's palsy. On the 3rd day after admission, he was diagnosed with left pontine infarction and suspected infarction of the left anterior inferior cerebellar artery. We propose that in similar cases, re-examination of imaging results should be considered, as diffusion-weighted imaging is characteristically prone to generate false-negative results in patients with early onset or posterior circulation infarction.

Inflammatory progressive multifocal leukoencephalopathy with human T-cell lymphotropic virus-1 coinfection.

A middle-aged man with progressive multifocal leukoencephalopathy (PML) in a human T-cell lymphotropic virus type-1 (HTLV-1) carrier on haemodialysis presented with mild dysarthria and ataxia. Brain MRI revealed asymmetric T2-hyperintense lesions in the cerebral white matter, cerebellum and brainstem. A small amount of JC virus (JCV) genome in cerebrospinal fluid was detected by PCR and cerebellar biopsy demonstrated JCV-DNA presence. Pathological findings showed demyelinating lesions and glial cells with mildly enlarged nuclei, accompanied by T-lymphocytes, neutrophils and plasma cell infiltration. The CD4+/CD8+ratio was 0.83. High-dose corticosteroid therapy was effective for inflammatory PML lesions, and the administration of mefloquine combined with mirtazapine led to favourable outcome. The encephalitis in this case is considered to have occurred secondarily to JCV infection in the presence of HTLV-1 infection. Therefore, it is crucial to investigate the presence of HTLV-1 in order to understand the aetiology of this brain inflammation.

Clinicoradiological features of probable chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described chronic inflammatory central nervous system disease. This case report describes a young female patient presenting with weakness in bilateral upper and lower limbs and tinnitus for 2 months. A neurological examination revealed signs of brainstem and cerebellar involvement. MRI brain showed characteristic features of CLIPPERS, with punctate and nodular enhancement in the pons and cerebellum. Differential diagnoses were systematically considered and excluded. The patient showed significant clinical and radiological improvement with steroid therapy. No clinical or radiological red flags occurred during the follow-up. This case underscores the critical role of integrating clinical and radiological findings to effectively diagnose and manage CLIPPERS. It emphasises the importance of ruling out alternative diagnoses through a thorough evaluation.

Primary catastrophic antiphospholipid syndrome in children with midbrain infarction: a case report.

Background: Catastrophic antiphospholipid syndrome (CAPS) is a multi-system autoimmune disease characterized by extensive thrombosis. Pediatric CAPS is extremely rare and associated with a high mortality rate, especially when midbrain infarction is involved. Hence, early diagnosis and prompt initiation of appropriate treatment for CAPS complicated by midbrain infarction are of utmost importance in achieving favorable outcomes. Case presentation: In this report, we present the case of a 14-year-old girl who presented with neurological symptoms and digestive system infection and was initially diagnosed with an "intracranial infection". After a series of rigorous diagnostic procedures, the patient was ultimately diagnosed with primary CAPS and was immediately transferred to the intensive care unit where she was treated with anticoagulation, glucocorticoids, intravenous immunoglobulin (IVIG) therapy, and multiple plasma infusions. Twenty-seven days after admission, the patient's condition improved with standardized treatment, and she was discharged and followed up regularly. Conclusion: This case report provides a description of the clinical features observed in a pediatric patient with CAPS and concurrent midbrain infarction, highlighting the crucial role of early diagnosis and timely treatment in influencing patient prognosis.

Effect of Maternal Diabetes Mellitus on Neonatal Hearing.

Introduction: Gestational diabetes is a potential risk factor for neonatal hearing loss. Increased circulating sugars in mothers during pregnancy can impairs the micro circulation and can cause congenital anomalies of the inner ear resulting in congenital hearing loss. This study attempts to find the incidence of neonatal hearing loss among diabetic mothers. Methodology: This was a case control study with 86 neonates of diabetic mothers as cases and neonates of non diabetic mothers(n = 86) as controls. Antenatal diabetic history and sugar values of mothers were documented. Hearing status of the neonates were tested using DPOAE test and ABR test. DPOAE test was done on 3rd day and those who did not get a positive response underwent 2nd DPOAE and also ABR test if 2nd DPOAE was negative. Results: All neonates underwent DPOAE test and few were lost on follow up. First and second DPOAE showed a statistically significant difference between cases and controls. All babies who underwent ABR test had abnormal waveforms. 98% of cases showed moderate and severe bilateral hearing loss whereas all controls had only mild bilateral hearing loss. Discussion: This study showed a significantly higher percentage of abnormal hearing outcome among neonates of diabetic mothers than non diabetic mothers. This could be because of the toxic effects of maternal hyperglycemia on developing auditory system of the fetus. This study emphasis the need for better glycaemic control in diabetic pregnancy, the importance of early and mandatory hearing screening in newborns of diabetic mothers.

A study to evaluate the burden of hearing loss and its correlation with risk factors among high-risk infants at a teaching institution, Jaipur.

Introduction: Hearing loss is a global issue of hearing disability and early detection and rehabilitation of hearing loss are important for the development of speech and language skills in hearing-impaired infants. There are multiple risk factors that aid in hearing loss but some are potential factors that contribute toward hearing loss in infants. The aim of this study was to assess the burden of hearing loss and its correlation with risk factors among high-risk infants at a teaching institution in Jaipur, Rajasthan. Method: This study was carried out after approval of institutional ethics committee on a total of 320 high-risk infants at RUHS College of medical sciences and associated hospitals. Hearing loss was assessed by brainstem evoked response audiometry (BERA). Statistical analysis of data was done by cross-tabulation analysis with Pearson correlation and quantile regression. Results: Out of 320 high-risk infants, 59.69% of infants had normal hearing, 9.09% Unilaterally hearing impaired, 20.31% were bilaterally mild-moderate hearing loss, and 10.94% had severe-profound deafness. The prevalence of important risk factors viz. hyperbilirubinemia, low birth weight, appearance, pulse, grimace, activity, and respiration score, meconium aspiration, respiratory distress, and ventilation greater than five days were 86%, 58.9%, 40%, 36%, 29%, and 22%, respectively. Conclusion: In high-risk infants, hearing loss is a common hearing disorder. Because of this, early diagnosis of hearing loss gives them the best chance of developing functional speech. Brainstem evoked response audiometry is a simple, reliable, and effective technique for the assessment of auditory functions in infants.

Deep Learning-based Approach for Brainstem and Ventricular MR Planimetry: Application in Patients with Progressive Supranuclear Palsy.

Purpose To develop a fast and fully automated deep learning (DL)-based method for the MRI planimetric segmentation and measurement of the brainstem and ventricular structures most affected in patients with progressive supranuclear palsy (PSP). Materials and Methods In this retrospective study, T1-weighted MR images in healthy controls (n = 84) were used to train DL models for segmenting the midbrain, pons, middle cerebellar peduncle (MCP), superior cerebellar peduncle (SCP), third ventricle, and frontal horns (FHs). Internal, external, and clinical test datasets (n = 305) were used to assess segmentation model reliability. DL masks from test datasets were used to automatically extract midbrain and pons areas and the width of MCP, SCP, third ventricle, and FHs. Automated measurements were compared with those manually performed by an expert radiologist. Finally, these measures were combined to calculate the midbrain to pons area ratio, MR parkinsonism index (MRPI), and MRPI 2.0, which were used to differentiate patients with PSP (n = 71) from those with Parkinson disease (PD) (n = 129). Results Dice coefficients above 0.85 were found for all brain regions when comparing manual and DL-based segmentations. A strong correlation was observed between automated and manual measurements (Spearman ρ > 0.80, P < .001). DL-based measurements showed excellent performance in differentiating patients with PSP from those with PD, with an area under the receiver operating characteristic curve above 0.92. Conclusion The automated approach successfully segmented and measured the brainstem and ventricular structures. DL-based models may represent a useful approach to support the diagnosis of PSP and potentially other conditions associated with brainstem and ventricular alterations. Keywords: MR Imaging, Brain/Brain Stem, Segmentation, Quantification, Diagnosis, Convolutional Neural Network Supplemental material is available for this article. © RSNA, 2024 See also the commentary by Mohajer in this issue.

A Case of Multifocal Ectopic Germinoma Manifesting with Medial Longitudinal Fasciculus Syndrome.

Introduction: Intracranial germinomas mainly arise in the pineal gland or neurohypophyseal region. The basal ganglia have been reported as the site of occurrence for ectopic germinomas, whereas other sites have been rarely described. We experienced a case of multifocal ectopic germinoma that arose in the septum pellucidum and the dorsal brain stem, not including the pineal gland, neurohypophysis, and basal ganglia of ectopic germinoma in a pregnant woman. Case Presentation: The patient initially presented to our institution with complaints of diplopia in the past 14 weeks of gestation, and imaging later revealed two intracranial neoplastic lesions, with one lesion involving the septum pellucidum and the other involving the dorsal brainstem. Both tumors were partially excised via a transcortical approach. Based on the results of pathology and immunohistochemistry, the patient was diagnosed with germinoma, and the intraoperative spinal fluid cytology was class V in Papanicolaou classification. The patient received three courses of ifosfamide, carboplatin, and etoposide together with whole-brain irradiation, which resulted in complete elimination of the tumors. No evidence of recurrence was identified after 18 months. Conclusion: The results illustrated the need to consider germinoma in the differential diagnosis if the lesions involve midline structures such as the septum pellucidum or dorsal brainstem. Given the rarity of germinoma arising outside the pineal gland and neurohypophyseal region, these findings provide key insights into the diagnosis and treatment of this disease.

Noninvasive Molecular Subtyping of Pediatric Low-Grade Glioma with Self-Supervised Transfer Learning.

Purpose To develop and externally test a scan-to-prediction deep learning pipeline for noninvasive, MRI-based BRAF mutational status classification for pediatric low-grade glioma. Materials and Methods This retrospective study included two pediatric low-grade glioma datasets with linked genomic and diagnostic T2-weighted MRI data of patients: Dana-Farber/Boston Children's Hospital (development dataset, n = 214 [113 (52.8%) male; 104 (48.6%) BRAF wild type, 60 (28.0%) BRAF fusion, and 50 (23.4%) BRAF V600E]) and the Children's Brain Tumor Network (external testing, n = 112 [55 (49.1%) male; 35 (31.2%) BRAF wild type, 60 (53.6%) BRAF fusion, and 17 (15.2%) BRAF V600E]). A deep learning pipeline was developed to classify BRAF mutational status (BRAF wild type vs BRAF fusion vs BRAF V600E) via a two-stage process: (a) three-dimensional tumor segmentation and extraction of axial tumor images and (b) section-wise, deep learning-based classification of mutational status. Knowledge-transfer and self-supervised approaches were investigated to prevent model overfitting, with a primary end point of the area under the receiver operating characteristic curve (AUC). To enhance model interpretability, a novel metric, center of mass distance, was developed to quantify the model attention around the tumor. Results A combination of transfer learning from a pretrained medical imaging-specific network and self-supervised label cross-training (TransferX) coupled with consensus logic yielded the highest classification performance with an AUC of 0.82 (95% CI: 0.72, 0.91), 0.87 (95% CI: 0.61, 0.97), and 0.85 (95% CI: 0.66, 0.95) for BRAF wild type, BRAF fusion, and BRAF V600E, respectively, on internal testing. On external testing, the pipeline yielded an AUC of 0.72 (95% CI: 0.64, 0.86), 0.78 (95% CI: 0.61, 0.89), and 0.72 (95% CI: 0.64, 0.88) for BRAF wild type, BRAF fusion, and BRAF V600E, respectively. Conclusion Transfer learning and self-supervised cross-training improved classification performance and generalizability for noninvasive pediatric low-grade glioma mutational status prediction in a limited data scenario. Keywords: Pediatrics, MRI, CNS, Brain/Brain Stem, Oncology, Feature Detection, Diagnosis, Supervised Learning, Transfer Learning, Convolutional Neural Network (CNN) Supplemental material is available for this article. © RSNA, 2024.

Treatment Modalities and Outcomes in Brainstem Cavernous Malformations: A Large Multicenter Observational Cohort Study.

BACKGROUND: Symptomatic brainstem cavernous malformations (BSCMs) pose a high risk of morbidity and mortality due to recurrent hemorrhage, warranting aggressive management. However, few studies have compared the effectiveness of different treatment modalities for BSCMs. We aimed to assess the association of treatment modalities with recurrent hemorrhage and neurological outcomes in patients with BSCM. METHODS: We conducted a retrospective cohort study using an observational registry database covering population of southwest and southeast China. Adult patients with BSCM were included and followed up between March 1, 2011, to March 31, 2023. We compared outcomes between microsurgery and stereotactic radiosurgery (SRS) in propensity score-matched case pairs, incorporating demographic, medical history, and lesion characteristics. The outcomes studied included recurrent hemorrhage and poor prognosis (defined as a Glasgow Outcome Scale score, <4). Absolute rate differences and hazard ratios (HRs) with 95% CIs were calculated using Cox models. RESULTS: Among 736 diagnosed patients with BSCM, 96 (48 matched pairs) were included after exclusions and propensity score matching (mean age, 43.1 [SD, 12.1] years; 50% women). During the median 5-year follow-up, no significant differences in recurrent hemorrhage (4.2% [microsurgery] versus 14.6% [SRS], HR, 3.90 [95% CI, 0.46-32.65]; P=0.21) and poor prognosis (12.5% [microsurgery] versus 8.3% [SRS], HR, 0.29 [95% CI, 0.08-1.08]; P=0.07) were observed between microsurgery and SRS recipients. Furthermore, either microsurgery or SRS correlated with fewer recurrent hemorrhage (HR, 0.09 [95% CI, 0.02-0.39]; P=0.001; HR, 0.21 [95% CI, 0.07-0.69]; P=0.01) compared with conservative treatment. CONCLUSIONS: In this study, both microsurgery and SRS were safe and effective for BSCM, demonstrated comparable outcomes in recurrent hemorrhage and poor prognosis. However, interpretation should be cautious due to the potential for residual confounding. REGISTRATION: URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2300070907.

Exploring Brainstem Structural Abnormalities: Potential Biomarkers for Panic Disorder.

Panic disorder (PD), characterized by recurrent and intense panic attacks, presents a complex interplay between psychological and neurobiological factors. Although the amygdala and hippocampus have been studied extensively in the context of PD, the brainstem's involvement remains relatively underexplored. This study aims to address this gap by examining structural abnormalities within specific brainstem regions, including the medulla, pons, and midbrain. The study sample population comprised twenty-one adult patients diagnosed with PD and an age-gender-education-matched control group. Utilizing rigorous inclusion and exclusion criteria, confounding factors related to comorbid psychiatric conditions and brain structure abnormalities were minimized. Our findings revealed a significant reduction in medulla volume among PD patients, a finding that persisted even after correcting for individual differences in total intracranial volume. The medulla's role in cardiovascular regulation and autonomic function, coupled with its involvement in fear responses, underscores its potential significance in the pathophysiology of PD. This study elucidates the medulla's structural abnormalities as a potential biomarker for PD. Understanding the role of the brainstem in PD could pave the way for more targeted and effective interventions for this condition.

Endovascular embolisation of posterior condylar canal dural arteriovenous fistula.

We describe a rare case of dural arteriovenous fistula (dAVF) of the posterior condylar canal in a man in his 30s who presented with recent onset headache and neck pain and subsequently acute intracranial haemorrhage. Radiological workup showed a medulla bridging vein draining dAVF of the right posterior condylar canal supplied by a meningeal branch of the right occipital artery. A dilated venous sac was seen compressing over cerebellar tonsil on the right side. There was acute haemorrhage in the posterior fossa and fourth ventricle. He was successfully managed with transarterial endovascular embolisation via a supercompliant balloon microcatheter without any complication. The balloon microcatheter effectively prevented reflux of the liquid embolic agent into the parent artery and vasa nervosa of lower cranial nerves.

Brain stem tumors in children less than 3 months: Clinical and radiologic findings of a rare disease.

PURPOSE: Brain stem tumors in children < 3 months at diagnosis are extremely rare. Our aim is to study a retrospective cohort to improve the understanding of the disease course and guide patient management. METHODS: This is a multicenter retrospective analysis across the European Society for Pediatric Oncology SIOP-E HGG/DIPG Working Group linked centers, including patients with a brainstem tumor diagnosed between 2009 and 2020 and aged < 3 months at diagnosis. Clinical data were collected, and imaging characteristics were analyzed blindly and independently by two neuroradiologists. RESULTS: Five cases were identified. No patient received any therapy. The epicenter of two tumors was in the medulla oblongata alone and in the medulla oblongata and the pons in three. For patients with tumor in equal parts in the medulla oblongata and the pons (n = 3), the extension at diagnosis involved the spinal cord; for the two patients with the tumor epicenter in the medulla oblongata alone (n = 2), the extension at diagnosis included the pons (n = 2) and the spinal cord (n = 1). Biopsy was performed in one patient identifying a pilocytic astrocytoma. Two patients died. In one patient, autopsy revealed a high-grade glioma (case 3). Three survivors showed either spontaneous tumor regression (n = 2) or stable disease (n = 1). Survivors were followed up for 10, 7, and 0.6 years, respectively. One case had the typical imaging characteristics of a dorsal exophytic low-grade glioma. CONCLUSIONS: No patient fulfilled the radiologic criteria defining a high-grade glioma. Central neuroradiological review and biopsy may provide useful information regarding the patient management.

Integrative care: acupuncture based neuromodulation therapy for diabetes and heart failure.

The relationship between heart failure and diabetes is intricate and bidirectional. Individuals with diabetes face an elevated risk of developing heart failure due to factors like insulin resistance, chronic inflammation, and metabolic irregularities. Elevated blood sugar levels can harm blood vessels and nerves, culminating in the buildup of fatty deposits in arteries, atherosclerosis, and hypertension, which significantly contribute to heart failure. Furthermore, diabetes can adversely impact the structure and function of the heart muscle, impairing its pumping capacity. Conversely, heart failure can also contribute to the onset of diabetes by disrupting the body's metabolic processes and amplifying insulin resistance. The complex interaction between these conditions mandates a comprehensive approach to managing individuals with both diabetes and heart failure, underscoring the importance of addressing both aspects for enhanced patient outcomes. Although existing pharmacological treatments are limited and frequently associated with undesirable side effects, acupuncture has established itself as a traditional practice with a legacy. It remains a supplementary option for treating cardiovascular diseases. Heart failure and diabetes are both heavily associated with chronic upregulation of the sympathetic nervous system, which has been identified as a pivotal factor in the progression of disease. Mechanistic interplays such as the attenuation of central nitric oxide signaling may interfere with the production or availability of nitric oxide in key areas of the central nervous system, including the brainstem and hypothalamus. This review will delve into the current understanding of acupuncture on the autonomic nervous system and offer insights into its potential role in the future treatment landscape for diabetes and heart failure.

Clinico-Radiological Correlation of Weber's Syndrome.

Weber's syndrome, named after Hermann Weber, is characterized by midbrain lesions often caused by strokes, resulting in ipsilateral third nerve palsy, including ptosis and pupillary abnormalities, and contralateral hemiplegia. We discuss a case of a 35-year-old lady with cognitive impairment, right hemiparesis, diplopia, left eye ptosis, and lateral eye deviation. MRI of the brain with contrast suggested an acute infarct in the left-sided paramedian region of the midbrain. The oculomotor nucleus and cerebral peduncle were both affected by an abrupt left-sided paramedian midbrain stroke. The participation of particular midbrain nuclei together with symptoms including drooping eyelids, diplopia, and limb paralysis suggested Weber's syndrome. An MRI study of the brain is the modality of choice in suspected stroke cases and is more sensitive when it comes to the brainstem lesions. A comprehensive neurological examination with a clinical diagnosis of Weber's syndrome before radiological investigations is of great help for localizing brain stem lesions and thus aids in early diagnosis and treatment.

Cerebellar progressive multifocal leucoencephalopathy identified by the shrimp sign.

Progressive multifocal leucoencephalopathy (PML) is a demyelinating disease caused by the John Cunningham (JC) virus, which may get reactivated under certain immunosuppressive states such as AIDS, immunomodulatory therapy and haematological malignancies. PML has been reported rarely even in immunocompetent individuals where no immunodeficiency was present. PML characteristically involves periventricular and juxtacortical white matter. Isolated cerebellar or brainstem PML may be seen rarely. We present a case of a man in his 70s who presented with rapidly progressive cerebellar ataxia, ptosis and bipyramidal signs. Investigations excluded a direct viral cerebellar infection, acute disseminated encephalomyelitis, paraneoplastic cerebellar degeneration or any structural cerebellar lesion. MRI PET study revealed the classical shrimp sign which raised the possibility of cerebellar PML, and the same was confirmed by a positive JC virus PCR in the cerebrospinal fluid. Our patient had no known immune-compromising state, but further workup revealed a low CD4 count suggestive of idiopathic CD4 lymphopenia. The case illustrates the importance of the shrimp sign on MRI, the possibility of cerebellar involvement of PML as well as the need to consider a differential diagnosis of PML even in individuals with no obvious immunocompromised state.

Presentation of basilar artery stroke secondary to patent foramen ovale: a diagnosis made with a 'selfie'.

We report the case of a woman in her late 20s, with no significant medical history, who was found unresponsive at home. Her mother revealed a 'selfie' sent to her by the patient 30 min prior to collapse which revealed bilateral ptoses. Initial brain imaging with non-contrast CT of the brain revealed nil of note. A multiphase CT angiogram revealed an acute basilar artery thrombosis. She underwent timely thrombolysis and was transferred for endovascular thrombectomy. Further evaluation with an aim to define the aetiology revealed the diagnosis of patent foramen ovale with a resultant paradoxical embolism. The differential diagnoses of unexplained rapidly evolving neurology with reduced Glasgow coma scale, and relevant appropriate investigations are discussed in this case report.