Atypical Causes Research Articles

Multimodality Imaging of Neurodegenerative Processes: Part 2, Atypical Dementias.

The purpose of this article is to describe the role of multimodality imaging in the evaluation of atypical neurodegenerative conditions. An imaging approach to the more common dementia disease processes was described in part 1. This article, part 2, briefly discusses current Centers for Medicare & Medicaid Services coverage for imaging patients with dementia and illustrates the basic concepts of combining anatomic, metabolic, and amyloid imaging in the evaluation of patients with atypical neurodegenerative dementia. Although these disease processes are rare, the growing repertoire of clinically available imaging techniques necessitates an understanding of their imaging patterns. Despite the rarity of these conditions, imaging of patients with neurodegenerative disorders is on the rise, and familiarity with the imaging appearances of these atypical causes is increasingly important.

Two Cases of Young Females Suffering From Stroke with Protein S Deficiency

“Young stroke” or “stroke with undetermined cause” is an interesting phenomenon. Though in the absence of any epidemiological study, or available statistical data, true prevalence or incidence of these types of clinical problems in our country cannot be determined, there is a growing concern among the clinicians about the emergence of such diseases in ourpopulation. There is even less familiarity of us with the protein S and problems arising from its deficiency. Though its role is well established in causing thrombophilia derived venous thrombosis, in recent days it has been implicated and recognized as an important factor causing arterial thrombosis and diseases like strokes, especially in the young. We present here two cases of young strokes, both females, who got admitted into same Medicine Unit in Dhaka Medical College Hospital within a year and subsequently, after exclusion of every possible typical and atypical causes, were found with Protein S deficiency.Bangladesh J Medicine Jan 2015; 26 (1) : 39-42

Septic Arthritis of the Hip in the Setting of Hemophagocytic Lymphohistiocytosis: A Case Report.

A twenty-two-month-old boy with septic hip arthritis had persistent elevated inflammatory markers and daily fevers despite multiple antibiotic regimens and repeated surgical debridements yielding negative cultures. After exhaustive work-up for other infectious, rheumatologic, and immunologic etiologies, he met diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH) and developed cultures positive for fungal hip arthritis. Following treatment for HLH and fungal hip arthritis, he improved and was discharged. No previous report in the literature specifically associates HLH with septic hip arthritis, to our knowledge. Surgeons should suspect underlying immunologic deficiencies and atypical infectious causes of septic arthritis when usual treatment modalities have failed.

Etiology of Corpus Callosum Lesions with Restricted Diffusion.

Infarction of the corpus callosum is rare, and other conditions can cause magnetic resonance imaging (MRI) restricted diffusion in the callosum, leading to diagnostic uncertainty. We sought to characterize the etiology of lesions with diffusion restriction in the corpus callosum. Callosal lesions with restricted diffusion were identified at our institution between January 2000 and December 2010. Radiographic and clinical data were reviewed to determine whether the lesion was vascular and if so, to identify the underlying mechanism. A total of 174 cases were reviewed in depth; 47 % were vascular and 53 % were nonvascular. Among vascular cases, atypical mechanisms of stroke (e.g., vasculitis/vasculopathy, hypercoagulable state) were most common (37 %), followed by cardioembolism (28 %). Vascular splenial lesions in particular were likely due to atypical causes of stroke. The most common nonvascular etiologies were trauma (44 %), tumor (22 %), and demyelination (15 %). Vascular lesions were more common in older, non-Caucasian patients with vascular risk factors. Nonvascular lesions were more likely to be found in association with T2-hyperintense cortical lesions, focal intraparenchymal enhancement, or edema/mass effect on MRI. More than half of lesions with diffusion restriction in the corpus callosum are due to a nonvascular cause. Clinical and radiographic characteristics can help distinguish vascular from nonvascular lesions in the corpus callosum. Nonvascular lesions are more likely to be seen in younger patients without vascular risk factors and are more often accompanied by enhancement and edema. Vascular lesions are most commonly due to atypical stroke etiologies, and these patients may require additional diagnostic testing.

Congenital Absence of the Pericardium

Congenital absence of the pericardium (CAP) is an uncommon finding previously recognized only post-mortem or during surgery. However, its incidence has been on the rise with the use of multiple contemporary imaging techniques. CAP can present with paroxysmal, left-sided chest pain and should be considered in the differential diagnosis of atypical causes of chest pain. We present the case of a 50-year-old male who presented with chest pressure, symptoms of heart failure, and was found to be in atrial fibrillation in whom partial absence of the left pericardium was diagnosed.

Atypical causes of cholestasis.

Cholestatic liver disease consists of a variety of disorders. Primary sclerosing cholangitis and primary biliary cirrhosis are the most commonly recognized cholestatic liver disease in the adult population, while biliary atresia and Alagille syndrome are commonly recognized in the pediatric population. In infants, the causes are usually congenital or inherited. Even though jaundice is a hallmark of cholestasis, it is not always seen in adult patients with chronic liver disease. Patients can have "silent" progressive cholestatic liver disease for years prior to development of symptoms such as jaundice and pruritus. In this review, we will discuss some of the atypical causes of cholestatic liver disease such as benign recurrent intrahepatic cholestasis, progressive familial intrahepatic cholestasis, Alagille Syndrome, biliary atresia, total parenteral nutrition induced cholestasis and cholestasis secondary to drug induced liver injury.

Cerebral air embolism from angioinvasive cavitary aspergillosis.

Background. Nontraumatic cerebral air embolism cases are rare. We report a case of an air embolism resulting in cerebral infarction related to angioinvasive cavitary aspergillosis. To our knowledge, there have been no previous reports associating these two conditions together. Case Presentation. A 32-year-old female was admitted for treatment of acute lymphoblastic leukemia (ALL). Her hospital course was complicated by pulmonary aspergillosis. On hospital day 55, she acutely developed severe global aphasia with right hemiplegia. A CT and CT-angiogram of her head and neck were obtained demonstrating intravascular air emboli within the left middle cerebral artery (MCA) branches. She was emergently taken for hyperbaric oxygen therapy (HBOT). Evaluation for origin of the air embolus revealed an air focus along the left lower pulmonary vein. Over the course of 48 hours, her symptoms significantly improved. Conclusion. This unique case details an immunocompromised patient with pulmonary aspergillosis cavitary lesions that invaded into a pulmonary vein and caused a cerebral air embolism. With cerebral air embolisms, the acute treatment option differs from the typical ischemic stroke pathway and the provider should consider emergent HBOT. This case highlights the importance of considering atypical causes of acute ischemic stroke.

Acute Myeloid Leukemia Presenting as Back Pain in a 12-Year-Old Boy

Acute Myeloid Leukemia Presenting as Back Pain in a 12-Year-Old Boy

New Concepts of Thrombotic Thrombocytopenic Purpura and a Strategy to Prevent its Relapse

In the past, thrombotic thrombocytopenic purpura (TTP) was defined as a syndrome of the pentad of thrombocytopenia, microangiopathic hemolytic anemia, neurologic deficits, renal abnormalities and fever. To include patients with incomplete features, the pentad definition was replaced by the triad of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and neurologic deficits; or the diad of thrombocytopenia and MAHA. None of these definitions provides a clear distinction of TTP from atypical hemolytic uremic syndrome (aHUS) or other causes of the syndrome of MAHA and thrombocytopenia or thrombotic microanangiopathy. This brief review describes a mechanistic definition of TTP, provides a framework for assessing the role of various co-morbid conditions in the pathogenesis of the syndrome of thrombocytopenia and MAHA, and summarizes new insights of the natural course of TTP. Based on these new insights, a strategy of ADAMTS13-guided preemptive rituximab therapy is proposed to prevent relapses in patients with acquired TTP. Thrombotic thrombocytopenic purpura (TTP) has been defined as a clinical syndrome of pentad (thrombocytopenia, microangiopathic hemolytic anemia [MAHA], neurological deficits, fever and renal abnormalities), triad (thrombocytopenia, MAHA, neurological deficits) or diad (thrombocytopenia and MAHA). In addition to this uncertainty, there was also no consensus on whether and how patients with prominent renal failure or co-morbid conditions should be excluded. The difficulty of defining TTP as a clinical syndrome arises from two facts: More than one disorder may cause the syndrome of diad, triad or pentad; and some patients of TTP do not present with thrombocytopenia or MAHA.

BNP-Erhöhung bei subduralem Hämatom - durch einen Biomarker in die Irre geführt

A 73-year-old man with a mechanical aortic valve and a history of congestive heart failure was admitted to our hospital with an unspecifically reduced general condition. Physical examination was normal according to age apart from mechanic valve closure tones and a 2/6 sytolic murmur at Erb's point. Inflammation markers were elevated (leukocytosis 22 100/μl, CRP 22 mg/dl ), there was mild anemia (hemoglobin 9.7 mg/dl) and digitoxin blood level was increased to 56 μg/l (therapeutic range 10-30 μg/l). Because NT-proBNP was highly elevated, further diagnostics focused on cardiac causes of BNP elevation despite missing clinical symptoms. Transesophageal echocardiography was inconspicuous and blood cultures were negative. Therefore an infection of unknown origin or an emerging endocarditis were presumed. Pragmatic treatment with antibiotics and diuretics as well as discontinuation of digitoxin led to normalization of leukocytes, CRP and digitoxin levels. But the patient's general condition deteriorated further, NT-proBNP rose to 37731 pg/ml and the patient became disoriented. On thorough questioning the patient's relatives stated that he had fallen 6 weeks previously. Computed tomography then revealed a large chronic subdural hematoma which had caused the NT-proBNP elevation. The patient was operated successful. In patients with elevated BNP and atypical symptoms neurological causes should be considered.

Kikuchi Disease

Introduction In the setting of fever of unknown origin and diffuse lymphadenopathy, it is important to rule out rheumatologic causes, malignancies, as well as atypical infectious causes. Fever of unknown origin and lymphadenopathy can be associated with a number of infectious etiologies, including herpes simplex virus, Epstein-Barr virus, cytomegalovirus, Bartonella henselae, Mycobacterium tuberculosis, Toxoplasma gondii, and Francisella tularensis. 1-3

The Index Case for the Fungal Meningitis Outbreak in the United States

Persistent neutrophilic meningitis presents a diagnostic challenge, because the differential diagnosis is broad and includes atypical infectious causes. We describe a case of persistent neutrophilic meningitis due to Aspergillus fumigatus in an immunocompetent man who had no evidence of sinopulmonary or cutaneous disease. An epidural glucocorticoid injection was identified as a potential route of entry for this organism into the central nervous system, and the case was reported to the state health department.

Abstract 223: Acute Ischemic Stroke in a 23-Year-Old Patient with Verrucous Endocarditis, Prothrombin Heterozygote Mutation, and a Patent Foramen Ovale: A Case Report and Literature Review

Background Stroke is the third leading cause of death and the leading cause of severe, long-term disability in the United States. Since the etiology of stroke in young adults is more heterogeneous, making a diagnosis is often a challenge requiring extensive clinical investigation. We report a case of acute ischemic stroke in a 23 year-old patient with multiple risk factors. Case Report A 23 year-old Spanish female with a history of tobacco abuse was brought to the Emergency room after she had a sudden onset of left-side weakness, slurring of speech, and lost of consciousness for a couple of minutes. Physical examination: left upper and lower extremities were completely flaccid with left facial weakness. MRI of head confirmed a right middle cerebral artery regional acute ischemic stroke. Transesophageal Echocardiogram revealed small granular densities on the mitral leaflets that consistent with atypical verrucous endocarditis and a patent foramen ovale (PFO). Hypercoagulable evaluation confirmed prothrombin gene mutation heterozygote. The erythrocyte sedimentation rate (ESR) was 75 mm/hour. All other tests were either negative or in normal range. Anticoagulation therapy was started with Heparin and then switched to Coumadin with an INR target of 2.5. Aspirin was also initiated. Discussion The differential diagnosis in young people (under 50 years) for potential etiology of ischemic stroke is broader than that for older adults. Atypical causes are more prevalent in this population, including cardiogenic cerebral embolus, hypercoagulable states, and autoimmune disease. Verrucous endocarditis is small thrombotic and nonbacterial lesions on the heart valves and endocardium, occurring frequently in systemic lupus erythematosus (SLE). However, hypercoagulable states and malignancy are often associated with the formation of verrucous endocarditis. Lesions are usually clinically silent. An embolic stroke may be the first feature to suggest the diagnosis. Since there was no evidence in malignancy, SLE, and antiphospholipid syndrome for our patient, hypercoagulable states should be considered as one of the risks for verrucous endocarditis. About 1-2% of the general population is heterozygous for the prothrombin gene mutation. In contrast, in Spain rates of 6% have been reported. It carries a 2 to 4 times increase in venous thrombosis and also increases the risk of arterial thrombosis (stroke and heart attack). Additionally, studies also show that inherited thrombophilic disorders in the pathogenesis of ischemic stroke might relate to congenital heart diseases such as Prothrombin G20210A variant and Factor V Leiden G1691A mutation might be associated with PFO. The prevalence of PFO in patients who have stroke of unknown cause may be about 40%. PFO also increases the rate of paradoxical thromboembolic stroke. This is particularly true in patients who have had a stroke at an age less than 50 years. Since our patient presents multiple risks for recurrent ischemic stroke, life-long anticoagulant therapy should be considered. Conclusion Acute ischemic stroke in a 23-years-old patient with verrucous endocarditis, prothrombin heterozygote mutation, and a PFO, but absent SLE has been rarely reported. Beside, the authors conclude that hypercoagulable testing and echocardiogram should be performed in young patients with stroke in order to provide us a better understanding of the etiology and the best treatment options.

Unusual aetiology of metabolic acidosis in pregnancy

ObjectiveWe present two cases of metabolic acidosis in pregnancy occurring over a one month period at Hillingdon Hospital.Case ReportA 22 year old primigravidae booked at 11/40, subsequent routine ultrasound scans...

An unusual differential for a pulseless trauma patient

Hemorrhagic shock is the most common reason to explain the inability to feel pulse in a trauma patient. However, clinicians should always suspect atypical causes for differential pulses in this population and Takayasu's arteritis (TA) is one such example. We report a case of aorto-arteritis in a patient who presented with trauma and was later diagnosed with TA. She had blood pressure discrepancy between upper and lower limbs noted upon her initial trauma evaluation.

Ischemic Stroke in Young Patients with Cardiac Abnormalities and Hypercoagulable State: 2 Case Reports and Literature Review to Assess Diagnostic and Prevention Options

Abstract 4663 BackgroundStroke is the third leading cause of death and the leading cause of severe, long-term disability in the United States. The incidence of cerebrovascular accident (CVA) in young adults has been increasing. Since the etiology of CVA in young adults is more heterogeneous, making a diagnosis is often a challenge requiring extensive clinical investigation. We report 2 cases of ischemic stoke in young adults with multiple risk factors. Case ReportNo. 1. A 46-year-old male presented to the ER with loss of consciousness. Past medical history was unremarkable. MRA confirmed occlusion of the left posterior cerebral artery. Transesophageal Echocardiogram (TEE) revealed a patent foramen ovale (PFO) and atrial septal aneurysm (ASA). Hypercoagulable evaluation confirmed increased IgM anticardiolipin antibody, a lupus anticoagulant, and heterozygous MTHFR (Methylenetetrahydrofolate reductase) C677T mutation. Anticoagulation therapy was started with Heparin and then switched to Coumadin. Aspirin was also initiated along with folic acid, Vitamin B6 and B12, and smoking cessation therapy. Unfortunately, the patient developed hemiparesis and dementia after stroke.No. 2. A 50-year-old female presented to the ER with headache and blurred vision for one hour. Patient had cerebrovascular accident (CVA) 7 years prior to that event. She has been taking aspirin. MRI confirmed encephalomalacia in the left cerebellar hemisphere. TEE revealed a PFO. During the PFO closure procedure, an atrioseptal defect and a myxomatous were diagnosed. Patient was directed to use clopidogrel for at least six months after procedure, and aspirin indefinitely. DiscussionThe differential diagnosis for potential etiology in young people (under 55 years of age) of CVA is broader than that for older adults. Ischemic strokes are much more common than hemorrhagic in this group of patients. The atypical causes are more prevalent in the younger population, including cardiogenic cerebral embolus, hypercoagulable states, and autoimmune disease needs to be considered. Cardiogenic cerebral embolus is the most common cause of stroke in young adults. Stroke can be associated with abnormalities of the atrial septum, specifically PFO, atrial septal defect (ASD), aneurysm, and cardiac myxomas. Studies show that the prevalence of PFO in patients who have stroke of unknown cause (cryptogenic stroke) may be about 40 percent. More specifically, PFO increases the rate of paradoxical thromboembolic stroke that occurs by allowing blood clots from the venous system to enter the arterial system. This is particularly true in patients who have had a stroke at an age less than 55 years. PFO closure procedures may help to identify underlying causes of CVA, as was discussed in case 2. Some studies have described an association between atrial septal aneurysm (ASA) and embolic strokes. The embolus might originate in an ASA or from a clot around the edges of a PFO. The mechanism of cerebrovascular events with ASA may be platelet/thrombus formation at the site of the aneurysm. Aspirin may be effective therapy for preventing CVA. Emboli from cardiac myxomas also can lead to cerebral ischemia, infarction, and aneurysm formation. Up to half of cardiac myxomas produce systemic emboli. Consequently, studies show that inherited thrombophilic disorders in the pathogenesis of stroke might relate to congenital heart diseases. The data suggests that Factor V Leiden G1691A mutation or Prothrombin G20210A variant may be associated with PFO. An increased prevalence of right-to-left shunts in patients with cerebrovascular accident CVA and activated protein C resistance has also been documented. Antiphospholipid Antibody Syndromes (APS) are recognized as independent risks for Cerebrovascular Accident (CVA). APS are associated with a heterogeneous group of disorders that result in hypercoagulable states involving arterial and venous thrombosis. Cerebral circulation is particularly affected in APS. ConclusionBased on these observations, the authors conclude that hypercoagulable testing should be performed in young patients with CVA. In addition, PFO closure procedures may be an important diagnostic tool that helps to identify a subset of patients in whom the etiology of CVA was not apparent. Disclosures:No relevant conflicts of interest to declare.

Viral and Atypical Bacterial Detection in Acute Respiratory Infection in Children Under Five Years

BackgroundAcute respiratory infection (ARI) is a leading cause of morbidity and mortality in children worldwide. This study aimed to determine the viral and atypical bacterial causes of different severities and clinical manifestations of ARI in preschool children from low-income families in North-East Brazil.MethodsClinical/demographic data and nasopharyngeal aspirates (NPA) were prospectively collected from children <5 years presenting with ARI over one year to a paediatric A&E department. Disease severity was grouped according to presence of lower respiratory tract signs, need for hospital admission and need for oxygen. Clinical manifestation of ARI was based on discharge diagnosis from hospital with four conditions predominating: bronchiolitis, pneumonia, episodic viral wheeze/asthma and upper respiratory tract infection. Multiplex PCR was used to detect 17 common respiratory viral and atypical bacterial pathogens in NPA.Findings407 children with a median age of eight months were recruited. Pathogens were detected in 85·5% samples with co-infection being particularly common (39·5%). Respiratory Syncytial Virus (RSV; 37%), Adenoviruses (AdV; 25%), Rhinoviruses (hRV; 19%), Bocavirus (hBoV; 19%), human Meta-pneumovirus (hMPV; 10%) and Mycoplasma pneumoniae (Mpp; 10%) were most prevalent. Detection and co-infection rates were similar in all severities and clinical manifestations of ARI apart from RSV, which was associated with more severe disease and specifically more severe cases of bronchiolitis, and Mpp, which was associated with more severe cases of pneumonia. Mpp was detected in 17% of children admitted to hospital with pneumonia.InterpretationThis study underlines the importance of viral and atypical bacterial pathogens in ARI in pre-school children and highlights the complex epidemiology of these pathogens in this age group. Generally, viruses and atypical bacteria were detected in all severities and clinical manifestations of ARI but RSV and Mpp were associated with more severe cases of bronchiolitis and pneumonia respectively.

Atypical causes of nontraumatic intracranial subarachnoid hemorrhage

Background To analyze the management and outcome of patients presenting with atypical causes of intracranial subarachnoid hemorrhage (SAH). Methods We performed a review of our last 820 nontraumatic-SAH patients and analyzed the management and outcome of patients where the SAH origin was not a ruptured aneurysm. The Glasgow Outcome Scale (GOS) was used to assess outcome 3 months after event. Results Thirty-two patients had atypical causes of SAH. In 15 patients with Hunt and Hess (H&H) scores from 1 to 3 without focal neurological deficit (FND), 8 perimesencephalic nonaneurysmatic SAH, 4 blood coagulation disorders, 1 sinus thrombosis, 1 vasculitis, and 1 unknown-origin-SAH (UOS) were diagnosed. Fourteen (93%) of these 15 patients were conservatively treated. In 17 patients with H&H scores from 3 to 5 and FND, 8 tumors, 1 cavernoma, 1 sinus thrombosis, 1 arteriovenous malformation, 1 blood coagulation disorders, 2 UOS, and 3 dural fistulas were diagnosed. Fifteen (88%) of these 17 patients were interventionally treated. The neurological condition 3 months later was good (GOS 4 and 5) in 12 of the 15 cases (80%) admitted with low-H&H scores, as well as in 13 of the 17 cases (76%) admitted with high-H&H scores. Three patients died and four developed a severe disability. Conclusions Patients presenting with atypical causes of SAH and high-H&H scores at admission are likely to harbor an intracranial organic process producing the bleeding. Despite this poor initial condition, their 3-month outcome can be similar to those of patients with low-H&H scores if the origin of the bleeding is properly treated.

Atypical infections of the prostate

Atypical infections of the prostate are infrequently recognized or cultured. However, clinical evidence points to their occult role in the pathogenesis of prostatitis. Atypical infections of the prostate can be caused by gram-positive and gram-negative bacteria, Mycoplasma, Chlamydia, fungi and Mycobacterium tuberculosis that are not classically associated with prostatitis. Increasing evidence suggests that viruses, protozoans, and various zoonoses also play an important role in prostatic infections. Bacterial 16S ribosomal DNA found in patients with chronic prostatitis suggests a bacterial inflammatory event that initiates an autoimmune process. Prostatitis may also cause elevated levels of prostate-specific antigen, a prostate cancer tumor marker. Hence, determination of an underlying infection becomes important in the evaluation of a patient with an abnormal prostate-specific antigen level. Awareness of atypical causes of infectious prostatitis improves understanding of challenges related to the diagnosis and treatment of patients with chronic prostatitis.

Severe community‐acquired pneumonia: an Australian perspective

Severe community-acquired pneumonia (CAP) is a common disease with a relatively high mortality. The initial treatment is empirical, based on a broad range of potential pathogens. There are minimal published data describing microbiological causes of pneumonia in Australia. To describe the aetiology and characteristics of severe CAP in patients requiring intensive care unit (ICU) admission, to identify factors predicting mortality and to audit current practices of investigation and antibiotic management of these patients from an Australian perspective. A retrospective analysis of patient case notes was performed for 96 consecutive patients admitted to two ICU with severe CAP. Data recorded included patient demographics, comorbidities, antimicrobial treatment, investigations and outcome (mortality, length of stay). Overall, mortality was 32%. A microbiological diagnosis was made in 46% of patients. The most frequent causative organisms were Streptococcus pneumoniae (13 cases), influenza A (9), Haemophilus influenzae (5) and Staphylococcus aureus (4); aerobic Gram-negative bacilli collectively accounted for five cases. Blood cultures were positive in 20% of patients. Seventy patients (73%) required mechanical ventilation and 61 patients (63%) required inotropic support. Laboratory abnormalities including acute renal failure, metabolic acidosis and coagulopathy were frequent. Factors associated with mortality on multivariate analysis were age, antibiotic administration prior to hospital presentation, delay in hospital antibiotic administration of more than 4 h, and presence of multilobar or bilateral consolidation on chest X-ray. Severe CAP requiring ICU admission was associated with a mortality rate of 32%, despite appropriate antimicrobial therapy including a beta-lactam and a macrolide antibiotic in most cases. Causative organisms identified were similar to those found in previous studies. High rates of viral causes (28% of identified pathogens) were noted. Low rates of legionellosis and other atypical causes were found, most probably due to a lack of systematic testing for these agents.