The crowned dens syndrome. Evaluation with CT imaging.

PURPOSE: The purpose of this study was to verify the value of computed tomography (CT) in the diagnosis of the "crowned dens" syndrome, not only in crystal deposition diseases, but also in other rheumatic or nonrheumatic conditions. MATERIALS AND METHODS: Thirty-eight patients (15 men and 23 women; mean age 55 years; age range 35-79) with neck pain were examined and divided into two groups: (1) patients already identified as rheumatic and referred for further investigation of the atlantoaxial region; (2) patients with symptoms confined to the cervical spine, with inconclusive radiographic findings. Unenhanced CT of the cervical spine (Tomoscan SR 7000 Philips, Eindhoven, Netherlands) was performed in all patients. There were 11 cases of rheumatoid arthritis (ten women and one man), two calcium pyrophosphate dihydrate crystal deposition disease (both women), one of systemic sclerosis (a woman), one of osteoarthritis (a man), one of seronegative arthritis (a man), four of neoplasm (one woman and three men) with suspected cervical involvement, one (a man) of haematological disease (lymphoma), one (a woman) of menopausal osteoporosis, ten (five men and five women) of recent or previous trauma with suspected involvement of the skull base and first cervical vertebrae and six of unknown painful cervical dysfunction (three men and three women). RESULTS: CT demonstrated calcific deposits around the dens in 12 patients (three men and nine women), in the transverse and alar ligaments, and in the anterior atlantooccipital membrane. CT revealed horseshoe- or crown-like calcification surrounding the odontoid process. In our series, other rheumatic diseases, especially rheumatoid arthritis, showed similar irregular calcifications of the atlantoaxial joint. Discussion. In calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, the spine may be the only site of involvement, generally asymptomatic. Crystals located in the transverse ligament of the atlas give rise to the crowned dens syndrome, usually in patients affected by severe degenerative lesions of the atlantoaxial joint and peripheral chondrocalcinosis. Symptoms may be absent, or a neurological compressive syndrome may develop. Symptoms tend to worsen with age. The diagnosis is not always easy, as the symptoms are similar to those of other diseases, such as meningitis, cervicobrachial pain, occipitotemporal headache, calcific tendinitis of the longus colli muscle, spondylodiscitis and retropharyngeal abscess. CONCLUSION: CT is the gold standard in identifying crowned dens syndrome, as it is able to depict the shape and site of calcification and any bone erosions. Radiography of other joints (wrist, knee, pubic symphysis) may help to ascertain whether the disease is due to calcium pyrophosphate dihydrate or hydroxyapatite crystals, and is therefore recommended for routine patient management. Magnetic resonance imaging (MRI) is indicated for the study of neurological complications.

Serotonin and serotonin receptor expression in the aorta of carotid intact and denervated newborns.

Pharmacological blocking of serotonin (5-HT) 5A receptors abolishes aortic ventilatory chemosensitivity of carotid body denervated (CBD) piglets [J. Appl. Physiol. 92 (2002) 893]. Accordingly, the purpose of the present study was to determine whether 5-HT and 5-HT receptors exist at aortic sites that are chemosensitive after CBD. Aortas from CBD and sham CBD rats and piglets and from aortic denervated (AOD) and combined AOD+CBD piglets were harvested, sectioned and then studied using immunohistochemistry and western blot techniques. 5-HT immunoreactivity in piglets and rats was concentrated in the endothelium and sub-endothelial areas in several aortic regions studied, and in some areas also in the adventitia. At the aortic chemosensitive site (descending aorta in CBD piglets and the ascending aorta in CBD rats), the immunoreactivity was greater (P < 0.05) than in other aortic regions and greater than in other groups studied. The 5-HT(5a) receptor was expressed only at the chemosensitive sites and only in aortic innervated piglets. We conclude that the data from this and a previous study [J. Appl. Physiol. 92 (2002) 893] suggest that a serotonergic mechanism contributes to the aortic ventilatory chemoreflex after CBD.

Effects of carotid and aortic chemoreceptor denervation in newborn piglets.

The objective of the present study was to test the hypothesis that in neonatal piglets there would be no hypoventilation after sham denervation or aortic denervation (AOD) alone, but there would be transient hypoventilation after carotid body denervation (CBD) and the hypoventilation would be greatest after combined carotid and aortic denervation (CBD+AOD). There was a significant (P < 0.05) hypoventilation in CBD and CBD+AOD piglets denervated at 5, 15, and 25 days of age. The hypoventilation in CBD+AOD piglets denervated at 5 days of age was greater (P < 0.05) than that of all other groups. Conversely, sham-denervated and AOD piglets did not hypoventilate after denervation. Injections of sodium cyanide showed that aortic chemoreceptors were a site of recovery of peripheral chemosensitivity after CBD. This aortic sodium cyanide response was abolished by prior injection of a serotonin 5a receptor blocker. Residual peripheral chemosensitivity after CBD+AOD was localized to the left ventricle. We conclude that 1) aortic chemoreceptors contribute to eupneic breathing in piglets that were carotid denervated at 5 days of age and 2) there are multiple sites of residual peripheral chemosensitivity after CBD.

Mortality after carotid body denervation in rats.

Carotid body denervation (CBD) in neonatal goats and piglets results in minimal irregular breathing and no fatalities. Redundancy and/or plasticity of peripheral chemosensitivity and a relatively mature ventilatory control system at birth may contribute to the paucity of CBD effects in these species. In the present study, we tested the hypothesis that CBD mortality would be greater in neonates of a less mature species such as the rat. We found that the mortality in rats denervated at 2-3 and 7-8 days of age was significantly higher (P < 0.05) than in sham-CBD rats. In all surviving rats, pulmonary ventilation during hypoxia was lower in CBD than in sham operated rats 2 days after denervation. In surviving rats denervated during the 7th and 8th postnatal days, there was also reduced weight gain and pulmonary ventilation during eupnea, including apneas up to 20 s in duration. However, the effects of CBD were compensated within 3 wk after denervation. Local injections of NaCN indicated that aortic chemoreceptors might have been one of the sites of recovery of peripheral chemosensitivity. We concluded that CBD has higher mortality in newborn rats than in other mammals, possibly because of the relative immaturity of these animals at birth. Nonetheless, in survivors there was enough redundancy and plasticity in the control of breathing to eventually compensate for the consequences of CBD.

Effects on breathing of carotid body denervation in neonatal piglets.

The purpose of these studies was to test the hypothesis that carotid chemoreceptor activity is necessary for postnatal maturation of the ventilatory control system. By using a lateral surgical access, 17 piglets were carotid body denervated (CBD) and 14 were sham denervated at 3-25 days of age. After surgery, there was no irregular breathing in any group. There was no significant hypoventilation when CBD was performed at less than 5 days of age (n = 5) and only a mild (arterial PCO(2) 5 Torr; P < 0.05) to moderate, transient (arterial PCO(2) 8 Torr; P < 0.5) hypoventilation in piglets denervated at 10-15 (n = 6) and 20-25 (n = 6) days of age, respectively. Three weeks after surgery, both breathing of a hypoxic gas mixture and jugular venous NaCN injections elicited a hyperpnea in the CBD piglets that was attenuated compared with that in sham CBD piglets. In the CBD piglets, there was no response to injections of NaCN in the carotid arteries, but there was a response to NaCN injected into the proximal descending aorta, suggesting the residual peripheral chemosensitivity was of aortic origin. Carotid chemoreceptor-intact piglets had carotid and aortic NaCN chemosensitivity by 2 days of age. The carotid response persisted for the 40 days of the study, but the aortic reflex persisted only until approximately 8 days of age. We conclude that 1) the major effect of CBD per se in neonatal piglets is age-dependent hypoventilation and 2) there is a high degree of plasticity in peripheral chemosensitivity in neonates that may contribute to minimizing the changes in breathing after CBD.

Effect of carotid body denervation on breathing in neonatal goats.

The objective of the present study was to determine in goats whether carotid body denervation (CBD) at 1-3 days of age causes permanent changes in breathing greater than those that occur after CBD in adult goats. Goats underwent CBD (n = 6) or sham CBD (n = 3) surgery at 1-3 days of age. In addition, one unoperated control animal was studied. Bolus intravenous injections of NaCN 2 days postsurgery verified successful CBD surgery. However, at 3, 11, and 18 mo of age, the CBD goats had regained a NaCN response that did not differ (P > 0.10) from that of intact goats. Intracarotid NaCN injections elicited a hyperpnea in the sham CBD but not the CBD goats. Only one animal exhibited highly irregular breathing [characterized by prolonged (>9-s) apneas] after CBD, and the irregularity disappeared by 3 mo of age. One CBD goat died at 35 days of age, and autopsy revealed that death was associated with pneumonia. After 3 mo of age, there were no statistically significant differences (P > 0.10) between sham and CBD goats in eupneic breathing, hypoxia and CO(2) sensitivity, and the exercise hyperpnea. It is, therefore, concluded that CBD at 1-3 days of age in goats does not appear to affect selected aspects of respiratory control after 3 mo of age, conceivably because of the emergence of other functional chemoreceptors that compensate for the loss of the carotid chemoreceptor.

Placental pathology casebook. Chorangiosis of the placenta increases the probability of perinatal mortality.

Two apparent acute problems that may occur in labor, nuchal cord and placental abruption, were associated with chorangiosis of the placenta. The importance of complete placental examination in perinatal mortality is re-emphasized. The association of apparent acute obstetrical conditions, e.g., nuchal cord and placental abruption with chorangiosis of the placenta, may be the cause of fetal-newborn deaths that were previously assumed to be issues of labor management.

Effect on breathing of ventral medullary surface cooling in neonatal goats.

The present study was designed to determine whether neurons near the ventral medullary surface (VMS) that are important to control of breathing in adult mammals are also important to control of breathing in neonates. In 7-day-old goats (n = 22), the VMS was surgically exposed under halothane anesthesia. Stainless steel thermodes (2 x 2 mm) were used to cool (20 degrees C) and thereby create neuronal dysfunction of discrete VMS sites. Bilateral cooling under anesthesia 0-2 or 2-4 mm lateral to the midline between the exit of cranial nerves VI and XII resulted in a reduction (P < 0.05) of breathing and most often in apnea. Cooling caudal or rostral to this area did not have a consistent effect on breathing. In 7-day-old goats (n = 8), 3 x 3-mm thermodes were chronically implanted bilaterally on the VMS surface between the exit of cranial nerves VI and XII. The goats recovered and were studied over several days thereafter. VMS cooling while the goats were awake caused breathing to decrease (P < 0.05), but apnea was never observed. The decrease was less (P < 0.05) than while the goats were anesthetized. After 10 s of cooling, the hypopnea while the goats were awake was uniform during eupnea, hypercapnia, hyperoxia, and hypoxia, but after 10 s of cooling, the decrease was relatively greater (P < 0.05) during hyperoxia and hypercapnia. These effects of VMS cooling are qualitatively the same as in adult goats; thus the data are consistent with mature VMS contribution to the control of breathing in neonatal goats.

Progressive immunodeficiency and fatal pneumonitis associated with human herpesvirus 6 infection in an infant.

Human herpesvirus 6 (HHV-6), an important opportunistic pathogen in immunocompromised patients, causes fatal pneumonitis, encephalitis, and bone marrow suppression. Its ability to infect and destroy T lymphocytes may allow it to synergize with the human immunodeficiency virus in the destruction of lymphoid tissues in patients with AIDS. We describe herein an infant who had an immunodeficiency associated with thymic atrophy and severe T lymphocytopenia who developed fatal pneumonitis due to HHV-6. Dense and disseminated infection of T lymphocytes with HHV-6 was also documented. In the absence of any other documented cause of immunodeficiency, we hypothesize that congenital infection of this infant with HHV-6 may have caused progressive destruction of her cellular immune system, leading to the fatal pneumonitis. Thus, HHV-6 infection may have been the cause of both her immunodeficiency and her fatal opportunistic infection.

Rapid quantitation of hemoglobin S by isoelectric focusing.

The feasibility of isoelectric focusing (IEF) to determine hemoglobin S (HbS) at a faster turn-around-time and to resolve the HbS and hemoglobin A (HbA) in presence of high concentrations of hemoglobin F (HbF) is evaluated. The IEF procedure is faster, and the results can be obtained in less than 45 minutes. The resulting data are comparable to gel electrophoresis. It is a superior procedure in resolving both HbS and HbA in the presence of high HbF and, therefore, a desirable technique to use for infants and children. Further, IEF is simpler than the gel electrophoresis, relatively inexpensive, easily adaptable for routine use, and suitable for "stat" conditions.

Neonatal hypotonia and cardiomyopathy secondary to type IV glycogenosis.

A neonate with deficiency of branching enzyme (glycogenosis type IV) presented symptoms of severe hypotonia pre- and postnatally, and dilated cardiomyopathy in early infancy. The classical clinical manifestation of liver cirrhosis was not present, although amylopectin-like inclusions were found in the hepatocytes. In contrast to a previous report, the neurons in the brain stem and spinal anterior horns contained PAS-positive, diastase-resistant deposits. The combined involvement of the muscles and motor neurones could account for the severity of hypotonia. The muscle biopsy, electromyogram and biochemical and enzyme assays were helpful in establishing the diagnosis.

GM1-gangliosidosis type 1 involving the cutaneous vascular endothelial cells in a black infant with multiple ectopic Mongolian spots.

GM1-gangliosidosis (GM1) is one of the metabolic storage diseases, of which a differential diagnosis requires an array of biochemical assays to determine the enzyme deficiency. This approach is not only time-consuming and costly but also unavailable to most hospital laboratories. However, a presumptive diagnosis of GM1 may be made on the basis of coarse facial feature, foamy endothelial cells in the cutaneous blood vessels and ectopic Mongolian spots, if present. A more definitive diagnosis of GM1 is then made on the demonstration of deficiency of GM1 beta-galactosidase in leukocytes, plasma or cultured skin fibroblasts. Thus, a battery of enzyme tests may be averted.

Anesthesia-induced rhabdomyolysis in infants with unsuspected Duchenne dystrophy.

Anesthesia-induced rhabdomyolysis in infancy may represent an unsuspected Duchenne dystrophy. In order to establish the diagnosis of this genetic disease more definitively, a dystrophin test is a requisite following the conventional creatine kinase test and light and electron microscopies of the muscle biopsy.

Optic chiasm glioma associated with inappropriate secretion of antidiuretic hormone, cerebral ischemia, nonobstructive hydrocephalus and chronic ascites following ventriculoperitoneal shunting.

An optic chiasm glioma may cause loss of vision, endocrine disturbances, hydrocephalus and cerebral ischemia due to its proximity to the pituitary, hypothalamus, III ventricle and internal carotids. A 3-month-old infant with optic chiasm glioma developed hypopituitarism and inappropriate secretion of antidiuretic hormone with plasma hypo-osmolality. The cerebrospinal fluid (CSF) protein concentration was markedly elevated. The impairment of fluid absorption via arachnoid villi and peritoneum by the high protein content, and reversed osmotic gradient between protein-rich CSF and hypo-osmolar plasma may have contributed to both nonobstructive hydrocephalus and recurrent ascites following ventriculoperitoneal shunting. Cerebral ischemia from carotid compression may have led to cerebral atrophy.

Limb body-wall complex in association with sirenomelia sequence.

Limb body-wall complex and sirenomelia sequence are uncommon birth defects and their association is extremely rare. Their overlapping manifestations and their concurrence in our patient suggest that they share a common cause and belong to a group of pathologically closely related conditions. Embryonic vascular disruption may be a common pathogenesis in both anomalies.

Hazards of mattresses, beds and bedding in deaths of infants.

Of 52 infants who had died suddenly and were referred to autopsy, nine had lain on adult water beds for the first time; five had died as a result of accidents; two had died on water beds; two were in beds with widely spaced slats; and one had died as a result of strangulation. Three deaths were due to overlying. Three other infants had been placed on sheepskin rugs for the first time and were found dead shortly thereafter. These infants ranged in age from 2 to 9 months, except for a severely mentally retarded nine-year-old with spastic paraplegia. We believe that a general warning should be issued concerning water beds and that soft bedding should not be used for infants. Infants should not be placed unattended or left to sleep on water beds; only beds recommended for infants should be used. Overlying of a young infant is most likely to occur on a water bed, or if the parent is obese or has consumed alcohol.

Inflammatory myofibrohistiocytic proliferation simulating sarcoma in children.

The term "inflammatory myofibrohistiocytic proliferation" (IMP) has been proposed to replace the conventional designations of plasma cell granuloma and inflammatory pseudotumor. Three cases of extrapulmonary IMP in children are reported, including an intracerebral lesion which has been formerly undescribed. In children, IMP may be associated with microcytic hypochromic anemia, hypergammaglobulinemia, and high erythrocyte sedimentation rate. In this clinical setting, differentiation of a rapidly growing but benign IMP from a bona fide sarcoma is of paramount importance.

Atypical total anomalous pulmonary venous connection: two channels leading to infracardiac terminations.

Reported is a rare case of total anomalous pulmonary venous connection (TAPVC) where veins from each lung joined a homolateral confluence. From each confluence, a vein descended into the abdomen, the vein from the right lung joining the ductus venosus, while the vein from the left joined the portal vein. In TAPVC to systemic veins, multiple connections are rare. Multiple connections are most common at supracardiac and cardiac levels, less common at supra- and infracardiac levels, and rare at cardiac and infracardiac levels. From the literature, it is evident that multiple connections at one body level, as in our case, are rare.

Oncocytic cardiomyopathy syndrome.

The case presented is the first report of oncocytic cardiomyopathy associated with congenital heart disease. The clinical presentation was typical of hypoplastic left heart syndrome, and the oncocytic cardiomyopathy was an unexpected finding at autopsy. The associated lesions of oncocytic metaplasia in thyroid and pituitary gland have been previously reported. Maternal serology and viral cultures from the infant were negative, indicating that the oncocytic lesions were not secondary to congenital viral infection. We support the theory that oncocytic cardiomyopathy is a hamartomatous lesion, and propose as a paradigm the association between cardiac rhabdomyoma and tuberous sclerosis. Careful follow-up of surgically "cured" oncocytic cardiomyopathy should uncover oncocytomas in other organs later in life.