Are the strokes in moyamoya syndrome associated with Down syndrome due to protein C deficiency?

Moyamoya syndrome has occasionally been seen in association with Down syndrome. We report a child with moyamoya syndrome and Down syndrome who was admitted with repeated episodes of strokes; his magnetic resonance imaging and magnetic resonance angiography findings confirmed the presence of occlusive cerebrovascular disease with basal collateral vessels. His protein C levels were significantly decreased during the stroke. Complete clinical recovery was seen during follow-up. This raises the possibility of a link between protein C deficiency and Down syndrome with moyamoya syndrome.

CT and MR patterns of hypoxic ischemic brain damage following perinatal asphyxia.

The objectives were to study the clinical and neurological abnormalities in children with cerebral palsy and to attempt to correlate the signs with radiological abnormalities detected by CT scan and/or MRI of the brain. In a prospective, hospital-based study, 65 children with cerebral palsy were examined neurologically and their perinatal history was reviewed. Their cranial CT scan, and/or magnetic resonance images were studied. The association between the gestational ages, perinatal history, neurological deficits, and the radiological appearances were studied. Of the 24 preterm-born and 41 term-born children, 23 had spastic diplegia; 57 per cent of these children has significant periventricular leucomalacia, which was more common among preterm-born children. Of the 13 children with hemiplegia, 12 had unilateral lesions on neuroimaging. Spastic tetraplegia was associated with extensive, bilateral, diffuse brain damage. Extrapyramidal cerebral palsy was far more common among term-born infants and 80 per cent of these showed significant abnormalities in the basal ganglia region. Ataxic cerebral palsy was an uncommon variety and there was no significant correlation between neurological signs and abnormalities on brain imaging. In conclusion, the radiological findings were closely related to the type of cerebral palsy and the neurological deficit except in the ataxic type. We believe that CT and MRI imaging are helpful in understanding the pathology and the timing of the lesion in cerebral palsy.

Massive intracerebral aspergillosis responding to combination high dose liposomal amphotericin B and cytokine therapy without surgery.

This report describes a patient with intracranial Aspergillus flavus infection in whom it was impossible to remove the fungal mass surgically. Progressive fungal infiltration of the optic nerves was reversed and the extensive intracranial fungal burden was managed successfully with combination antifungal-immunomodulatory therapy alone.

MR and other imaging methods in the investigation of mycetomas.

PURPOSE: To report features of mycetomas (actino- and eumycetoma infection), which belong to the so-called rare bone infections, as evaluated by MR and other imaging methods and to assess chemotherapy treatment. MATERIAL AND METHODS: Twenty patients (average age 57 years) were diagnosed by different modalities. Analyses of 57 plain films, 31 three-phase bone scans, 28 CT and 35 MR examinations were performed. The MR protocol included T1-weighting without and with contrast, T2-weighted, proton density and fat suppressing sequences. RESULTS: Signs of chronic osteomyelitis were seen in plain films of 10 patients (50%), but the healing process was difficult to assess. Bone scintigraphy was positive in 12 patients (60%). In 14 patients (70%), CT could demonstrate bone lesions, but the healing process was difficult to estimate in 4 patients. MR imaging provided accurate diagnostic information in 15 cases (75%). In 16 patients (80%), small lesions could be identified due to grains, which seemed to differentiate mycetoma from other infections and tumorous lesions. MR examination gave definitive answer about the healing process in 18 cases (90%). CONCLUSION: MR investigation was superior to the other imaging techniques in the evaluation of mycetoma and the assessment of therapy.

Abnormal myelin formation in rhizomelic chondrodysplasia punctata type 2 (DHAPAT-deficiency).

The case of a Yemeni girl with isolated peroxisomal acyl-CoA:dihydroxyacetonephosphate acyltransferase (DHAPAT) deficiency is reported. She had rhizomelic chondrodysplasia punctata, microcephaly, failure to thrive, delayed motor and mental development, and spastic quadriplegia. Deficient de novo plasmalogen synthesis in her fibroblasts as a result of low DHAPAT activity was found, while her very-long-chain fatty acid profile, phytanic acid concentration, alkyl-dihydroxyacetonephosphate synthase (alkyl-DHAP synthase) activity, and peroxisomal 3-ketoacyl-CoA thiolase protein were normal. A mutation in her DHAPAT complementary DNA resulted in the substitution of an arginine residue in the protein at position 211 by a histidine (R211H). Magnetic resonance imaging showed abnormal white matter signal in the centrum semiovale involving the arcuate fibers, while the corpus callosum was normal. DHAPAT and alkyl-DHAP synthase initiate the synthesis of plasmalogens, which are major constituents of myelin phospholipids. The reported girl's abnormal formation of myelin is probably related to the inadequacy of plasmalogen biosynthesis, which is likely to be due to deficient DHAPAT activity.

Novel missense mutation in the L1 gene in a child with corpus callosum agenesis, retardation, adducted thumbs, spastic paraparesis, and hydrocephalus.

Corpus callosum agenesis, retardation, adducted thumbs, spastic paraparesis, and hydrocephalus (CRASH syndrome) is an X-linked recessive disorder caused by mutations in the neuronal cell adhesion molecule L1 (LICAM) gene. L1 plays a key role in axon outgrowth and pathfinding during the development of the nervous system. We describe the case of a boy from the United Arab Emirates who presented with CRASH syndrome. Scanning the L1 gene of the patient resulted in the discovery of a novel missense mutation: transition of a G (guanine) to T (thymine) at position 604 (G604-->T), which results in conversion of aspartic acid to tyrosine at position 202 (D202Y) of the L1 protein. It is very likely that the cerebral dysgenesis is due to the abnormal structure and function of L1.

Bilateral frontoparietal polymicrogyria and epilepsy.

Two patients with bilateral frontoparietal polymicrogyria are reported. Severe developmental delay, mental retardation, spastic tetraplegia, and seizures were the main clinical features. Magnetic resonance imaging revealed a bilateral thick cortex with irregular gyri and a festoonlike gray-white matter junction. Bilateral frontoparietal polymicrogyria may represent a further form of the bilateral polymicrogyria syndromes in addition to perisylvian and parasagittal parieto-occipital polymicrogyria.

Autosomal recessive micrencephaly with simplified gyral pattern, abnormal myelination and arthrogryposis.

The clinical courses, neuroimaging and muscle biopsy findings of two infants born to an inbred Arab family are described. They had a syndrome of micrencephaly with simplified gyral pattern, abnormal myelin formation and arthrogryposis. Increased variation of fiber size was seen in the muscle biopsy, creatine kinase, however was normal. Large areas of muscle were replaced by adipofibrous tissue. The infants had dysmorphic features consistent with the fetal akinesia/hypokinesia sequence. The abnormalities were suggestive of microlissencephaly probably associated with a dysgenetic process in the muscles. The syndrome showed an autosomal recessive inheritance.

Joubert's syndrome: new cases and review of clinicopathologic correlation.

The authors report on seven patients, six males and one female, with Joubert's syndrome who underwent developmental evaluation, neurologic and ophthalmologic examinations, and magnetic resonance imaging of the brain. All patients had severe developmental delay, hypotonia, impairment of smooth visual pursuit, and saccadic eye movements. Six had jerky eye movements and ptosis was observed in two patients and retinal dystrophy in one. The posterior lobe of the vermis was absent in all patients and the small rudimentary anterior lobe lacked fusion in the midline, with cleft formation in five patients. Malformation of the pontomesencephalic junction, with prominent superior cerebellar peduncles and deep interpeduncular fossa, was observed in all patients. Abnormal cerebellar-brainstem and cerebellocortical connections because of the lack of the posterior vermis and dysplasia of the deep cerebellar nuclei might be responsible for the abnormal eye movements and retarded development in Joubert's syndrome. Correlation between radiologic findings and clinical symptoms and the possible role of abnormal patterning of the midbrain-hindbrain by homeotic genes during embryonic development are reviewed.

Absent pituitary gland and hypoplasia of the cerebellar vermis associated with partial ophthalmoplegia and postaxial polydactyly: a variant of orofaciodigital syndrome VI or a new syndrome?

We report two sibs with features overlapping those of orofaciodigital syndrome type VI (Varadi syndrome). Both presented at birth with oculomotor abnormalities, dysmorphic facial features, and dysgenesis of the cerebellar vermis. There were minimal oral manifestations (high arched palate) in both of them and one had postaxial polydactyly of both hands and one foot. In addition, there was evidence of aplasia of the pituitary gland on MRI scan in both of them with evidence of hypopituitarism. Both responded well to hormone replacement therapy with improvement in their linear growth and mental ability. These cases may represent a new autosomal recessive midline defect syndrome with features overlapping OFDS VI. Alternatively the features in these children could represent variability within OFDS VI.

Mediobasal and mantle defect of the prosencephalon: lobar holoprosencephaly, schizencephaly and diabetes insipidus.

An infant is described who had a combination of lobar holoprosencephaly and open-lip schizencephaly. Midline fusion of the basal ganglia was associated with bilateral absence of abundant parts of the brain mantle. Agenesis of the corpus callosum, hypoplasia of the optic nerves and chiasm, absence of the septum pellucidum, posterior pituitary and olfactory bulbs were further components of the malformation. Blindness, intractable seizures, spastic tetraplegia, somatomental retardation and diabetes insipidus were the main clinical features. A defect in the induction of the mediobasal part of the prosencephalon and failure of cell proliferation can be responsible for this complex malformation. Recent results of homeobox gene research relevant to the development of the prosencephalon are discussed.

Microlissencephaly.

An inbred Arab family with three neonates affected by microlissencephaly syndrome is reported. Brain magnetic resonance imaging in the index case revealed very thin brain mantle with agyria-pachygyria, agenesis of the corpus callosum, and hypoplasia of the brainstem and cerebellum. All three neonates had microcephaly, arthrogryposis multiplex congenita, and micropenis. The presence of three affected newborn infants in a consanguineous family suggests an autosomal-recessive mode of inheritance of this syndrome. The spectrum of microlissencephaly syndrome is reviewed.

Further delineation of Nevo syndrome.

Nevo syndrome is an autosomal recessive syndrome characterised by prenatal overgrowth, joint laxity, kyphosis, wrist drop, spindle shaped fingers, and volar oedema. Four children from two families have been reported previously. We report two further children from two unrelated Arab families from two different tribes. Both presented at birth with hypotonia, joint laxity, kyphosis, wrist drop, spindle shaped fingers, and volar oedema. Both have delayed motor development at the ages of 2 years 10 months and 3 months respectively. Cognitive development is normal in one, and the other case appears to be developing normally at 3 months of age. One has, in addition, a wide spinal canal on MRI of the spine indicating some degree of dural ectasia. This report brings the total number of children reported with this syndrome to six from four families; three of these families are Arab. This indicates that the gene for this syndrome is probably commoner in Arabs than in other populations.

Abnormal myelination in peroxisomal isolated dihydroxyacetonephosphate acyltransferase deficiency.

The cranial magnetic resonance imaging findings in three siblings with nonrhizomelic chondrodysplasia punctata due to isolated dihydroxyacetonephosphate acyltransferase (DHAP-AT) deficiency are reported. Areas of high signal intensity in a patchy distribution on the T2-weighted images were detected in the centrum semiovale in the eldest patient (a 6-year-old girl). The white matter of the second child (a 5-year-old boy) was spared, whereas the youngest sibling (a 2-year-old boy) manifested very severe white matter abnormalities. DHAP-AT catalyzes the first step in the synthesis of plasmalogens, which are major constituents of myelin. Defective plasmalogen synthesis may have contributed to abnormal myelin formation in 2 patients. Because the clinical presentation of the child without detectable defect in myelination was similar to that of his siblings, the neurologic signs observed in isolated DHAP-AT deficiency cannot be attributed solely to the disturbances in the myelin formation.

Agyria-pachygyria: cerebral perfusion studies by 99mTc-HMPAO SPECT [corrected].

Cerebral perfusion was investigated in three patients with agyria-pachygyria by using 99mTc-HMPAO SPECT in order to study the distribution of blood flow. Diffuse cortical hypoperfusion was found in all three infants. The visual cortex was not identifiable in two of the cases. The basal ganglia and cerebellum were prominent by their normal high activity, while tracer uptake was very low in the thalamus. The possible role of improper development of interneuronal connections and abnormal vascular pattern in background of the perfusion defect is discussed.

Regional cerebral blood perfusion in children with hemiplegia: A SPECT study.

Fourteen children with spastic hemiplegia of various etiology: cerebral palsy (seven cases, five with porencephalic cyst); stroke with small deep infarcts (two); hemiconvulsion-hemiplegia-epilepsy syndrome (three); traumatic brain injury (two), were investigated by 99mTc-HMPAO SPECT. Localized and remote perfusion abnormalities were studied. Hypoperfusion corresponding to CT abnormalities was found in each group, but the perfusion deficit extended beyond the boundaries of anatomical defects, most prominently in cases with widespread unilateral epileptic discharges. Ipsilateral cerebellar diaschisis was observed in patients with early cerebral insult (who had porencephalic cyst of pre- or perinatal onset) and crossed cerebellar diaschisis was noted in a patient who sustained traumatic brain injury at a later age. Diaschisis in the overlying cortex, thalamus and basal ganglia was noticed in several cases. Although clinical symptoms or signs could not be unequivocally attributed either to the size of the perfusion defects beyond the boundaries of lesions shown by CT or to the diaschisis, the findings may contribute to reveal age-related abnormal perfusion patterns.

Controlled trial of a geriatric case-finding and liaison service in an emergency department.

OBJECTIVE: To evaluate the effects of a program of case-finding and liaison service for older patients visiting the emergency department. DESIGN: Nonrandomized controlled trial with systematically assembled intervention cohort and matched control group. SETTING: An urban teaching hospital. PARTICIPANTS: There were 385 intervention subjects aged 65 years and older and 385 control subjects matched by day of visit, gender, and age within 5 years. INTERVENTIONS: Geriatric medical, dental and social problems were identified in intervention subjects by a geriatric nurse clinician using well validated assessment instruments during a 30-minute evaluation. Recommendations were made to the patient, family, and attending emergency department physician, and attempts were made to arrange appropriate follow-up services. MEASUREMENTS: Frequency with which geriatric problems were identified in intervention subjects; physician, patient, and family compliance with recommendations; and mortality, institutionalization, health status, use of medical and social services, presence of an advanced directive, and quality of life at 3-month follow-up. RESULTS: Sixty-seven percent of patients were dependent in at least one activity of daily living, 82% had at least one geriatric problem identified, and 77% reported at least one unmet dental or social support need. The cost of identifying geriatric and dental/social issues was $5 and $1, respectively, for each problem. Physicians compiled with 61.6% of suggestions, and patients and families complied with 36.6% of recommendations. Mortality and nursing home residence proportions at 3 months were not significantly different (9.3% vs 9.7% and 5.0% vs 2.5% in intervention and control groups, respectively). Intervention subjects reported more difficulty communicating (21% fair or poor ability vs 13%, P = 0.2) than did control subjects. There were strong trends for fewer subsequent visits to emergency departments (0.26 intervention vs 0.39 control, P = .06) and more advance directives in the intervention group (6.7% intervention vs 2.9% control, P = .07). There was no statistically or clinically significant difference in any other health outcome. The number of new dental or social services initiated per patient over the 3-month follow-up was nearly identical (1.7 in the intervention group vs 1.5 in the control). Results in subjects aged 75 years and older and those discharged home from the emergency department were essentially identical to those in the main group. CONCLUSIONS: Numerous previously unrecognized geriatric medical and social problems can be detected in older persons visiting the emergency department. Despite this, an emergency department-based geriatric assessment and management program failed to produce improved outcomes. This suggests that either disease acuity is an overwhelming factor in subsequent outcome or, alternatively, more control over medical and social service delivery during and after the emergency department visit than was demonstrated in this program will be required before successful outcomes can be assured.

Unrecognized delirium in ED geriatric patients.

To determine the sensitivity of an emergency physician's conventional evaluation compared with the validated Confusion Assessment Method (CAM) regarding the recognition of acute confusional states (delirium) in elderly Emergency Department (ED) patients, a cohort of 385 patients presenting to an urban teaching hospital ED was systematically assembled. Patients had to be conscious, able to speak and older than 64 years of age. After the ED physician had examined the patient and test results had been obtained, a series of geriatric assessment results, including one for the likely presence of delirium, was made available to the ED physician; however, no result was specifically highlighted. All patients were assessed by an attending ED physician in the customary fashion. In addition, a study nurse interviewed patients using the CAM and followed patient outcomes for three months. The ED record for all patients with delirium or "probable" delirium, as determined by the CAM, were reviewed for physician diagnosis and disposition to determine how often delirium had been recognized by the emergency physician. Thirty-eight of the 385 patients screened (10%) met criteria for delirium or "probable" delirium; ED charts were complete for 35 of these, which constituted the study sample. The ED diagnosis included delirium or an acceptable synonym in 6 (17%) of these patients. In the 21 patients (62%) admitted to the hospital, the most common ED diagnosis was infection "rule out sepsis" (n = 7). Six of 13 patients discharged (46%) were diagnosed as "status post fall" without evidence of significant injury.(ABSTRACT TRUNCATED AT 250 WORDS)