A case with juvenile rheumatoid arthritis who developed cerebral vasculitis and venovascular hypertension]

On November, 1997, a 15-year-old boy visited our hospital because of headache, fever and arthralgia. He was treated with 5 mg/day of prednisolone thereafter. On October 21, 1998, he was admitted because of remittent fever and multiple arthralgia and diagnosis of juvenile rheumatoid arthritis (JRA) was made. He was also found to have hypertension of 210/110 mmHg, and soon developed ptosis of the eye, facial paresis and perceptive deafness of the right side. Cerebrospinal fluid showed protein of 98 mg/dl and mildly elevated IgG, IgA and IgM levels with normal cell count. Brain MRI examination revealed multiple cerebral lesions in the frontal, parietal and cerebellar areas on the right, whose cause was thought to be vasculitis. Renal angiography demonstrated a right renal artery stenosis, compatible with renovascular hypertension. He was treated with 60 mg of prednisolone per day, which brought about a satisfactory improvement of the above rheumatic and neurologic signs. On November 17, 1998, he received a follow-up study of MRI, which failed to show any cerebral lesions, supporting the effectiveness of prednisolone. An angiotensin converting enzyme inhibitor successfully normalized hypertension and renin activity in serum, although renal blood flow did not increase.     

The cerebral hemorrhage-producing cystatin C variant (L68Q) in extracellular fluids.

A variant of the normal extracellular cysteine protease inhibitor cystatin C (L68Q-cystatin C), is the amyloid precursor in hereditary cystatin C amyloid angiopathy (HCCAA). It has been suggested that the mutation causes cellular entrapment of L68Q-cystatin C in vivo and that the variant protein is not secreted to extracellular fluids. In order to test this hypothesis, we used matrix-assisted laser desorption ionization time-of-flight mass spectrometry in an effort to demonstrate the presence of L68Q- along with wildtype cystatin C in plasma and cerebrospinal fluid (CSF) of HCCAA-patients. Plasma from all five investigated HCCAA-patients contained both L68Q- and wildtype cystatin C. The presence of approximately equal amounts of cystatin C dimers and monomers was demonstrated in plasma from HCCAA-patients, whereas only monomers could be found in normal plasma. L68Q-wildtype-cystatin C heterodimers seem to be present in the dimeric cystatin C population. CSF from six HCCAA-patients also contained cystatin C-dimers and monomers, but the dimeric fraction was minute. CSF from control patients did not contain dimeric cystatin C. These results suggest that the milieu of L68Q-cystatin C is important for its stability and dimerization status and that certain milieus might hinder its further development into oligomers, amyloid fibrils and other precipitating aggregates.     

A patient with meningeal carcinomatosis accompanied by a small pituitary metastatic lesion from gastric cancer who developed cerebral salt wasting syndrome

A 68-year-old man with disturbed consciousness had repeatedly developed light-headedness and dizziness since the summer of 1996 and was admitted to a hospital for detailed examinations on October 8, 1996. On admission, he weighed 49 kg and showed subclinical hypothyroidism with low T3 syndrome. The adrenal function and serum electrolytes were normal. Since the stool samples were positive for occult blood, gastroscopy was performed. Examination of the biopsy specimens demonstrated gastric cancer. On October 21, blood examination showed hyponatremia (127 mEq/l). On October 22, marked disturbance of consciousness developed. On October 24, the serum Na level further decreased to 116 mEq/l. On November 8, he was referred to our hospital. On admission, his skin and tongue showed marked dehydration, and severe disturbance of consciousness and neck stiffness were observed. The central venous pressure was 4 cmH2O. In the cerebrospinal fluid, atypical cells were observed, and a diagnosis of meningeal carcinomatosis was made. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was excluded because of marked dehydration, a normal blood ADH level, and because plasma osmotic pressure was greater than urinary osmotic pressure. Considering the possibility of cerebral salt wasting syndrome (CSWS) or hypoadrenocorticism, Na supplementation and drip infusion of prednisolone (20 mg/day) were performed. The serum Na has normalized (140.1 mEq/l), and his consciousness improved. He died of aggravation of the general condition on December 16. Pathological examination demonstrated a small metastatic lesion in the infundibular part of the pituitary gland and a small metastatic lesion in the parenchyma of the bilateral adrenal glands. However, since neither hypotension nor hypoglycemia was observed before treatment, and the blood cortisol level and the serum K level were normal, hypoadrenocorticism was excluded. Hypoaldosteronism was also excluded because of a normal serum K level. CSWS has been reported to be caused by head trauma, subarachnoid hemorrhage, or trans-sphenoidal pituitary operation. This patient is a rare case of CSWS developed in the presence of meningeal carcinomatosis accompanied by a small pituitary metastatic lesion from gastric cancer. The aged with decreased ability to retain water and sodium in the body are more susceptible to CSWS than the young. In the aged with central hyponatremia, the possibility of CSWS should be considered, and early diagnosis and treatment are necessary.     

Clinical diagnosis of cerebral amyloid angiopathy: Validation of the Boston Criteria

Cerebral amyloid angiopathy is a disorder in which deposition of amyloid within the arterial media and adventitia leads to intracerebral hemorrhage. Diagnosis during life has been hampered by the requirement for post-mortem examination for definitive diagnosis. The Boston Criteria for the diagnosis of cerebral amyloid angiopathy-related hemorrhage were developed in 1995 and 1996 in order to meet the need for a standardized set of diagnostic criteria that can be applied to living patients. Using a combination of clinical, radiologic, and pathologic data, these criteria reliably differentiate lobar intracerebral hemorrhage into categories of possible, probable, or definite based on the likelihood of underlying cerebral amyloid angiopathy. These criteria will be crucial for disease classification for future clinical studies.     

Correction

In the publication, “Human cystatin C expression and regulation by TGF-β1: implications for the pathogenesis of hereditary cystatin C amyloid angiopathy causing brain hemorrhage” by V Emilsson, L Thorsteinsson, O Jensson and G Gudmundsson which appeared in Amyloid: Int J Exp Clin Invest 3: 110-118 (1996), the final 10 references were omitted. They are listed below.     

Vivax malaria: a rare cause of thalamic bleed

Most common cause of thalamic bleed is hypertension; other causes are arteriovenous malformation, aneurysm, bleeding diathesis, drugs, amyloid angiopathy, tumor etc. We present a case of Plasmodium vivax (P. vivax) malaria with unusual site of bleeding i.e. left thalamus of brain. To the best of our knowledge, this is the first reported case of thalamic bleed caused by vivax malaria in absence of severe thrombocytopenia/disseminated intravascular coagulation (DIC).     

Increased body temperature accelerates aggregation of the Leu-68-->Gln mutant cystatin C, the amyloid-forming protein in hereditary cystatin C amyloid angiopathy.

Hereditary cystatin C amyloid angiopathy is adominantly inherited disorder, characterized by dementia, paralysis, and deathfrom cerebral hemorrhage in early adult life. A variant of the cysteineproteinase inhibitor, cystatin C, is deposited as amyloid in the tissues of thepatients and their spinal-fluid level of cystatin C is abnormally low. Thedisease-associated Leu-68-->Gln mutant (L68Q) cystatin C has been produced inan Escherichia coli expression system and isolated by use of denaturing buffers,immunosorption, and gel filtration. Parallel physicochemical and functionalinvestigations of L68Q-cystatin C and wild-type cystatin C revealed that bothproteins effectively inhibit the cysteine proteinase cathepsin B (equilibriumconstants for dissociation, 0.4 and 0.5 nM, respectively) but differconsiderably in their tendency to dimerize and form aggregates. While wild-typecystatin C is monomeric and functionally active even after prolonged storage atelevated temperatures, L68Q-cystatin C starts to dimerize and lose biologicalactivity immediately after it is transferred to a nondenaturing buffer. Thedimerization of L68Q-cystatin C is highly temperature-dependent, with a rise inincubation temperature from 37 to 40 degrees C resulting in a 150% increase indimerization rate. The aggregation at physiological concentrations is likewiseincreased at 40 compared to 37 degrees C, by approximately 60%. These propertiesof L68Q-cystatin C have bearing upon our understanding of the pathophysiologicalprocess of hereditary cystatin C amyloid angiopathy. They might also be ofclinical relevance, since medical intervention to abort febrile periods ofcarriers of the disease trait may reduce the in vivo formation of L68Q-cystatinC aggregates.     

Cases from the Osler Medical Service at Johns Hopkins University

PRESENTING FEATURES: A 70-year-old African American man was admitted with a history of fever, chills, and malaise of several days' duration. His past medical history was notable for end-stage renal disease requiring hemodialysis, coronary artery disease, and aortic stenosis requiring a bioprosthetic aortic valve replacement. On the day of admission, the patient was noted to have a shaking chill while undergoing dialysis through his catheter and was admitted to the hospital. He complained of pain at the catheter insertion site, shortness of breath, and dyspnea on exertion, but denied chest pain. On physical examination, the patient had a temperature of 100.4 degrees F, with a heart rate of 64 beats per minute, blood pressure of 127/72 mm Hg, and an oxygen saturation of 97% on room air. He was a mildly obese man in no apparent distress. He had shotty cervical lymphadenopathy and a right subclavian dialysis catheter in place, with erythema and pus at the entry site. His jugular venous pressure was 10 cm H(2)O. Lung examination showed bibasilar rales. Heart sounds were normal, with no rub or gallop. He had a 2/6 systolic ejection murmur best heart at the left sternal border as well as a 3/6 holosystolic murmur at the apex that radiated to his left axilla. Examination of the abdomen and extremities was unremarkable. The patient's neurological examination was unremarkable, and he was alert and oriented to person, place, and time. Laboratory studies showed an elevated white blood cell count of 16,700 cells/microL. His blood urea nitrogen level was 43 mg/dL and his serum creatinine level was 4.9 mg/dL. Multiple blood cultures grew methicillin-resistant Staphylococcus aureus. An admission, chest radiograph showed no infiltrate. An admission electrocardiogram showed normal sinus rhythm with first degree atrioventricular block, left anterior fascicular block, and left ventricular hypertrophy. shows rhythm strips from lead II electrocardiograms 5 months before admission (top), on admission (middle) and 5 days after admission (bottom). What is the diagnosis?     

A case of nonarteritic anterior ischemic optic neuropathy with hypertension, diabetes mellitus, hyperlipidemia and severe stenosis of the internal carotid artery

A 76 year-old man had had hypertension, diabetes mellitus and hyperlipidemia since 1985, and bruit in his left neck since 1993. He had abrupt decrease in left visual acuity on November 24, 2005, and visited an ophthalmologist. On November 28, his corrected visual acuity was 1.0 in the right and 0.1 in the left. The examination of optic fundi showed ear-side edema of the left optic disk. Fluorescence examination of the left optic fundus showed delay in early filling and later hyperfluorescence. Goldman visual field examination showed horizontal lower semiblindness. Since he did not complain of eye pain, his blood examination showed no reaction of inflammation, and he had hypertension, diabetes mellitus and hyperlipidemia, anterior ischemic optic neuropathy was diagnosed. The treatment with aspirin, alprostadil and prednisolone transiently improved the optic fundi and visual acuity, but his left visual acuity returned to 0.1. Carotid ultrasonography showed 95 percent stenosis in the left internal carotid artery. As there is no established treatment for ischemic optic neuropathy, the management of risk factors is most important.     

A case of cerebral venous angioma with paresis of the left arm and face

A 75-year-old woman was admitted to our hospital because of sudden onset of paresis in her left arm and face. She had untreated hypertension and hyperlipidemia. When she came back home after playing with children in the park, she felt weakness in her left hand. On admission, physical examination revealed that her blood pressure was very high (200/102 mmHg). Only slight weakness in her left arm and left facial palsy were recognized neurologically. An electroencephalogram showed normal findings. Brain CT and MRI revealed a venous angioma near the right central sulcus. Gadolinium-DTPA enhanced MRI showed a group of small radiating veins (so called "the caput medusae sign") connected to the venous angioma. The remaining symptoms decreased with the normalization of blood pressure. It is suggested the intracranial motor tracts of the face and arm in the precentral gyrus are adjacent to the location of this venous angioma. The dilation of venous angioma due to high blood pressure was thought to cause the paresis of face and arm in this patient.     

Pheochromocytoma of the urinary bladder revealed with cerebral hemorrhage

The case was a 51-year-old man, who has been undergoing treatment with oral medication for hypertension for three years. The patient was admitted to the author's clinic for hemorrhage in the left putamen. He was diagnosed as having primary pheochromocytoma of the bladder from such symptoms as paroxysmal blood pressure elevation after urination, mild increase in catecholamine levels before and after urination, and from the results of 131I-MIBG scintigraphy, and cystoscopy, and underwent excision of the bladder tumor. Upon endocrinological examination, only mild increases in catecholamine levels were found. Therefore, constant monitoring of blood pressure and 131I-MIBG scintigraphy were useful for a definitive diagnose.     

Multiple metastases from renal carcinoma 15 years after nephrectomy

A 72-year-old man was admitted to our hospital complaining of an axillary mass. He underwent left total nephrectomy for renal cell carcinoma (RCC) 15 years previously (in 1990). Since further evaluation yielded no evidence of extra renal metastases, he was followed up in the outpatient clinic. On admission, there was a hard tumor in the right axilla. Ultrasonography demonstrated a vascular tumor with a smooth surface, 26 by 24mm. Laboratory findings were generally close to normal, including tumor markers. Chest contrast-enhanced dynamic CT showed that the tumor was enhanced. Furthermore, abdominal contrast-enhanced dynamic CT revealed some enhancing lesions within the right side of the rectus muscle of abdomen and pancreas head as well. Open simple axillary mass biopsy was performed on August 2 and the tumor was histologically confirmed as a metastasis of the RCC to the axillary. His overall status was normal, and he underwent an operation for the pancreas tumor and the tumor in the rectus muscle of the abdomen. On histological examination, both excised specimens were found to be metastases of RCC. During 2 years follow-up period in the outpatient clinic, additional metastasis has not been observed in any organ. Since this case confirms the potential of RCC for late and multiple distant metastases, careful long-term follow-up after radical nephrectomy is needed.     

Cortical petechial hemorrhage, subarachnoid hemorrhage and corticosteroid-responsive leukoencephalopathy in a patient with cerebral amyloid angiopathy.

We describe a 69-year-old woman who developed subacute onset cognitive decline after hitting the left side of her head. Cerebral spinal fluid showed yellowish discoloration with highly elevated protein content. FLAIR MRI revealed diffuse high signal intensity in all cortical sulci, and leptomeningeal enhancement in the left cerebral hemisphere was seen in the T1 image after contrast administration. She was treated with a corticosteroid. Consciousness disturbance was temporarily relieved but again worsened, resulting in an apathetic state due to communicating hydrocephalus. A shunt tube was placed in her right lateral ventricle. A brain biopsy disclosed multiple cortical microbleeds and heavy deposition of Abeta-immuoreactive amyloid on vascular walls. Inflammatory mononuclear cells surrounded a few leptomeningeal vessels. After the operation her condition further deteriorated and she fell into a coma. MRI showed diffuse swelling of the right cerebral white matter. She again received high-dose corticosteroid and gradually recovered during the following 2 months. On MRI the vast majority of abnormal signals in the right cerebral white matter disappeared. An initial manifestation of this patient was possibly caused by multiple microhemorrhages from fragile cortical and subarachnoid vessels with Abeta-amyloid deposition, which was triggered by head trauma. CAA-related inflammation possibly worsened this condition. Additionally, surgical intervention for communicating hydrocephalus might have induced cerebral amyloid angiopathy (CAA)-related leukoencephalopathy in her right cerebral hemisphere. These CAA-derived manifestations are unusual and high-dose corticosteroids seems to be useful for vascular events in CAA patients.     

Cases from the Osler Medical Service at Johns Hopkins University: cardiac valvular lesions in Wegener's granulamatosis

Presenting features

A 65-year-old man presented to the emergency department with hemoptysis and hematuria. During the preceding 3 weeks, he had developed fevers, weakness, and myalgias that were increasingly debilitating. He subsequently developed frank hemoptysis and gross hematuria over 3 days. He denied contact with persons who were ill, recent travel, or dental procedures. His past medical history was unremarkable except for elevated serum cholesterol levels, for which he had been taking simvastatin for many years.On presentation, he was acutely ill, with a temperature of 38.8°C, a pulse of 90 beats per minute, a blood pressure of 132/88 mm Hg, and a respiratory rate of 18 breaths per minute. Examination of the head and neck revealed episcleritis and no oral ulcers. Examination of the heart was normal. Chest examination demonstrated bilateral coarse breath sounds with diffuse rhonchi. Skin examination revealed palpable purpura over the extensor surface of the right elbow.Laboratory studies included the following values: serum urea nitrogen, 158 mg/dL; creatinine, 11.7 mg/dL; total leukocyte count, 16.1 × 10³/mL; and erythrocyte sedimentation rate, >130 mm/h. Urinalysis was notable for 35 red blood cells per high-power field. A chest radiograph showed patchy infiltrates in the right upper and lower lobes. An electrocardiogram (ECG) revealed normal sinus rhythm at a rate of 94 beats per minute with normal intervals.The patient was admitted to the hospital with a presumptive diagnosis of vasculitis. He was treated with broad-spectrum antimicrobial agents, prednisone, and cyclophosphamide, in addition to beginning hemodialysis. Antimicrobial therapy was discontinued when blood cultures remained negative at 48 hours. The clinical diagnosis of Wegener’s granulomatosis was confirmed by an antinuclear cytoplasmic antibody titer of 1:80 and antiproteinase 3 (PR3) antibodies of 143 units (positive >30 units). A skin biopsy specimen demonstrated a small vessel vasculitis consistent with the diagnosis.The patient’s symptoms improved gradually, and he was discharged on day 13 with outpatient hemodialysis. During the next 3 days, his strength increased, and he was able to walk longer distances. On the fourth day after discharge, he suffered a ventricular tachycardic arrest at the initiation of hemodialysis. He was admitted to the intensive care unit after a prolonged resuscitation effort, but he remained unresponsive. His ECG was unchanged, and troponin I assay did not suggest myocardial infarction. Blood cultures remained negative. A transthoracic echocardiogram demonstrated normal left ventricular function and no valvular abnormalities. After 10 days, he showed no neurologic improvement. The family decided to withdraw ventilatory support, and he died quickly.What is the diagnosis?     

Cerebral amyloid angiopathy-related hemorrhage in a middle-aged patient with Down's syndrome

A patient with Down's syndrome (DS) died of cerebral hemorrhage at age 52. At autopsy, a large sub-cortical hematoma was present in the right frontal lobe, and microscopic examination showed numerous senile plaques and neurofibrillary tangles in an extensive area of neocortex and also disclosed heavy involvement of vascular walls by amyloid deposition. These senile plaque and vascular amyloid deposits were specifically stained with an antibody to Aβ. His APOE genotype was ?4/?4. This is a rare case of DS with cerebral amyloid angiopathy (CAA)-related cerebral hemorrhage. Genetic factors, such as APOE genotype, conceivably determine the risk of vascular rupture in individuals with CAA, even among patients with DS.     

A surgical case of cerebral hemorrhage in a patient with factor XI deficiency

A 63-year-old man suddenly presented with right hemiplegia and was taken to our hospital. Computed tomography (CT) scan revealed subcortical hemorrhage of the left parietal lobe. He had no medical history except hypertension; thus, it initially appeared to be a typical hypertensive hemorrhage. However, blood analysis showed an abnormally elevated activated partial thromboplastin time. One hour after admission, his Glasgow Coma Scale fell from 14 to 11. We performed an echo-guided stereotaxic removal of the hematoma. He improved immediately and was diagnosed with congenital factor XI (FXI) deficiency a few days after surgery. FXI deficiency, described as hemophilic syndrome C, rarely manifests as spontaneous bleeding, but surgical intervention has been known to manifest as bleeding. This case highlights the importance of evaluation of coagulopathies in patients with intracerebral hemorrhage before surgery, and, in cases wherein blood analysis results suggest coexisting coagulation disorders, less invasive surgical methods would likely lead to good outcomes.     

Klebsiella pneumoniae liver abscess associated with septic spinal epidural abscess

A 56-year-old Japanese man with hypertension presented with a 10 days history of high fever, right and left upper quadrant tenderness. An abdominal ultrasonography and computerized tomographic scan revealed a large collection in the right lobe of the liver that was consistent with an abscess. A drainage catheter was placed and purulent fluid was drained. Cultures of the fluid and blood were positive for a strain of ampicillin-resistant Klebsiella pneumoniae. Six days after admission, paraplegia and urinary retention were found. On the neurological examination, deep tendon reflexes of the lower extremities were absent bilaterally. Magnetic resonance imaging scan detected thoracic spinal epidural abscess and paraspinal abscess. He received the emergent decompressive laminectomy. Culture of surgical specimen grew ampicillin-resistant K. pneumoniae. The patient was treated with biapenem intravenously. Thereafter, clinical symptoms improved gradually and he was removed to the professional hospital to continue rehabilitation for gait disturbance on hospital day 147.     

Pure amnesia due to the right capsular genu infarction

A 77-year-old right-handed woman was admitted to our hospital with memory disturbance. Neurological examination was normal except for amnesia. Neuropsychological tests showed severe impairments in verbal and visual memories. Brain MRI revealed a fresh lacunar infarction in the genu of the right internal capsule. Decreased perfusion in the right thalamus and frontal lobe on (99m)Tc-ECD SPECT was attributable to disconnection of the thalamo-cortical tract by infarction. We consider that the patient's amnesia in this case was induced by infarction of the capsular genu, which includes some fibers from the anterior and inferior thalamic peduncles. Our findings demonstrated that lacunar infarction in the genu of the right internal capsule caused severe and persistent amnesia.     

Severe community-acquired Acinetobacter pneumonia]

A 62-year-old man with atrial fibrillation, hypertension, and fatty liver was admitted to a hospital in October 2002 complaining of productive cough and fever up to 38 degrees C for 2 days. He was a heavy smoker and drank alcohol regularly. He was dyspneic at rest, and chest radiography showed lobar pneumonia in the right upper lobe. Despite the administration of antibiotics, his condition deteriorated rapidly, and he was transferred to our hospital on the next day. On admission, he had multi-lobar pneumonia, septic shock, and disseminated intravascular coagulation. Despite the ventilatory support and the administration of carbapenem, macrolides, and catecholamine, he died 9 hours after admission. Later, all cultures from sputum and blood grew Acinetobacter species. Although community-acquired Acinetobacter pneumonias are rarely reported in Japan, physicians must be aware of this disease because of its fulminant clinical course and high mortality.     

Multiple atrial ball thrombi with stalk mimicking myxoma without valve disease: a case report

A 77-year-old man with atrial tumors was admitted to our hospital. He had no history of dyspnea, palpitation, or chest pain. He had a history of hypertension and atrial fibrillation without valve disease. Transthoracic and transesophageal echocardiography showed floating ball tumors with stalks from the right atrium (28 X 31 mm), the interatrial septum (16 X 11 mm), and the left atrial appendage (14 X 8 mm). The tumors were surgically removed and histologic examination of these tumors confirmed organization thrombus. This case of multiple atrial ball thrombi illustrates the problems with differentiation of myxoma and thrombus.