Nitric oxide mediates caerulein-induced suppression of locomotor activity

Congenital muscular dystrophy (CMD) is one of the most frequent dystrophies of childhood, which is commonly characterized by neonatal muscle impairment with or without clinical evidence of central nervous system involvement. Several variants of CMD have been described and the disease has recently been classified into five clinically distinct forms: the two classical CMDs with and without deficit of the laminin M chain (merosin), the Fukuyama CMD described in Japanese patients and recently linked to the chromosome 9q31-33, the clinically more severe Walker-Warburg syndrome and the rare muscle-eye-brain disease described in Finnish patients. The most of these forms have central nervous system involvement. This is usually not seen in the classical merosin positive CMD, but can be very severe in the others. Here we describe a 3-year-old Mediterranean child with clinical and histopathological signs of CMD, normal expression of merosin, severe clinical and radiological evidence of central nervous system involvement without defects of neuronal migration or brain malformations and without ocular anomalies. This report suggests that new forms of CMD and cerebral involvement can still be recognized and confirms the heterogeneity of this group of infantile diseases.     

Activated protein C resistance and deficiencies of antithrombin III, protein C or protein S and the risk of thromboembolic disease in users of oral contraceptives

The congenital muscular dystrophies (CMDs) comprise a heterogeneous group of muscle disorders with onset in utero or during the first year of life. Several forms of CMD show various types of brain involvement in addition to a muscular dystrophy. Two forms are defined at the molecular level: merosin deficient-CMD caused by mutations in the LAMA2-gene on chromosome 6q2. Fukuyama congenital muscular dystrophy (FCMD) is prevalent in Japan and caused by an as yet unidentified gene on chromosome 9q31. At least two further forms of CMD with brain involvement are nosologically well defined: Walker--Warburg-CMD is characterized by lissencephaly type 11, eye dysgenesis and muscular dystrophy. This autosomal recessive disorder is fatal or results in complete lack of development. A similar but much milder phenotype with pachygyria of the brain, various degrees of eye changes and milder muscular dystrophy that is compatible with achievement of simple motor milestones has been described under the name of muscle-eye-brain disease (MEB) in Finland. A number of nosologically less distinct forms of muscular dystrophy have been outlined such as 'pure' CMD without brain involvement, CMD with cerebellar hypoplasia or CMD type Ullrich with hyperelasticity of the distal joints. Several other CMD phenotypes are known, some of which are suggestive of more distinctly separate nosological entities due to their occurrence in siblings or due to a characteristic pattern of clinical, histopathological and imaging features, and await further clarification.     

Structure and function of the serine-protease subcomponents of C1: protein engineering studies

We reviewed neuroradiologic findings of Fukuyama congenital muscular dystrophy (FCMD) and correlated them with the known neuropathology. All patients showed thick and bumpy cortices with shallow sulci corresponding to polymicrogyria, and approximately half of the patients showed pachygyric cortex with smooth surface corresponding to type II lissencephaly. The two types of cortical dysplasias presented characteristic distributions: the former demonstrated frontal lobe involvement in all and parietotemporal lobe involvement in some, whereas the latter involved the temporo-occipital lobes. Most patients showed prolonged T1 and T2 signal in the white matter, which was indistinct in neonates and infrequently seen in adolescents. Cerebellar polymicrogyria depicted as disorganized cerebellar foliation accompanying cysts were found more than 90% of the patients. In conclusion, brain MRI demonstrates findings consistent with the known neuropathology of FCMD. The detection of the two types of cerebral cortical dysplasia with characteristic distribution and cerebellar abnormalities is helpful in the differential and early diagnosis.     

Preserved merosin M-chain (or laminin-alpha 2) expression in skeletal muscle distinguishes Walker-Warburg syndrome from Fukuyama muscular dystrophy and merosin-deficient congenital muscular dystrophy

The merosin M-chain (or laminin-alpha 2) is one of three subunits of laminin-2 which is highly expressed in striated muscle and peripheral nerve. Complete lack of laminin-alpha 2 expression in skeletal muscle is the hallmark of one form of congenital muscular dystrophy which is characterized by dysmyelination of the central nervous system (CNS), links to chromosome 6q2 and is common among Caucasians. Laminin-alpha 2 expression was also found to be significantly reduced in Fukuyama congenital muscular dystrophy which links to chromosome 9q3. We report consistently preserved laminin-2 expression, including laminin-alpha 2, as detected by immunofluorescence in skeletal muscle from five patients with Walker-Warburg syndrome which is characterized by congenital muscular dystrophy and, in addition, type II lissencephaly or pachygyria, defective CNS myelination, and ocular dysgenesis. These findings show that in spite of partial phenotypic overlap between Fukuyama CMD and Walker-Warburg syndrome the two disorders are nosologically separate disease entities. They also exclude that Walker-Warburg syndrome is allelic to the common form of congenital muscular dystrophy with laminin-alpha 2 deficiency.     

Fetal central nervous system anomalies: MR imaging augments sonographic diagnosis

PURPOSE: To evaluate fetuses with sonographically suspected central nervous system anomalies to determine the frequency with which obstetric magnetic resonance (MR) imaging adds clinically useful information to that provided by ultrasonography (US). MATERIALS AND METHODS: US and MR images and diagnoses in 18 pregnant women were reviewed and compared by two radiologists. Postnatal physical examination and imaging findings and fetal autopsy results were standards. Referring physicians were questioned as to how the additional information provided by MR imaging changed patient counseling. RESULTS: In 10 (55%) patients, MR imaging demonstrated 11 additional findings. These findings were agenesis of the corpus callosum (n = 4), cerebellar hypoplasia (n = 2), cortical cleft (n = 2), polymicrogyria (n = 1), porencephaly (n = 1), and partial agenesis of the septi pellucidi (n = 1). In seven (39%) patients, additional information provided by MR imaging altered counseling. In one case of suspected agenesis of the corpus callosum, diagnosis at MR imaging was at least partially incorrect. CONCLUSION: US and MR imaging are complementary imaging methods in the evaluation of high-risk pregnancy. When a central nervous system anomaly is suspected at US, MR imaging may demonstrate additional findings that can alter patient counseling.     

Pharmacokinetics of pamidronate disodium in patients with cancer with normal or impaired renal function

Among the variable manifesting conditions of neuronal migration disorders, mental retardation, motor disturbance and epilepsy are the main features of developmental disabilities. We analyzed the relationship between clinical symptoms and magnetic resonance (MR) images, including surface anatomy scan (SAS). Thirty nine patients (23 males, 16 females; mean age 6.1 years) with neuronal migration disorders were studied. The diagnoses were cerebral palsy in 23 cases, mental retardation in 4. West syndrome in 4, Fukuyama type congenital muscular dystrophy (FCMD) in 6. Walker-Warburg syndrome in 1 and Dubowitz syndrome in 1. Cortical dysplasias were classified into the following 7 groups, mainly based on the SAS findings: complete agyria (AG 1), mixture of agyria and pachygyria (AG 2), bilateral complete pachygyria (BP 1), diffuse pachygyria with marked widening of the bilateral superior frontal gyrus (BP 2), unilateral pachygyria with hemispheric atrophy or hemimegalencephaly UP), focal cortical dysplasia (FP) and other findings such as solitary schizencephaly (Others). Most cases of AG 1 and AG 2 showed spastic quadriplegia (6/7) and symptomatic generalized epilepsy (5/7), whereas cases of BP1 showed spasticity only in 1/8 and epilepsy in 7/8. Hemiplegia was observed in 6/7 of UP, 2/8 of FP and 2/4 of Others. Partial epilepsy was observed in 2/7 of UP and 1/8 of FP. Intellectual level was variable in BP 1, UP, FP and Others, but all cases showed severe mental retardation in AG 1, AG 2 and BP 2. BP 2 was observed in all cases of typical FCMD (5/5). The birth weight was less than 2,500 g in 6/7 of UP. The structural findings well correlated with clinical symptoms and epileptic seizure types. The surface anatomy scan was a very useful technique for detecting cortical dysplasias.     

Clinical and radiographic diagnosis of occlusal caries: a study in vitro

We report on the autopsy study of a premature boy with multiple joint contractures who died soon after birth of severe lung hypoplasia. Muscle histology showed PAS-positive vacuoles, and electronmicroscopy revealed massive subsarcolemmal and intermyofibrillar accumulation of glycogen. Biochemical analysis of fresh-frozen muscle tissue disclosed increased glycogen content and a complete lack of phosphofructokinase (PFK) activity. The brain showed focal cerebral and diffuse cerebellar white matter gliosis, and patchy loss of internal granular and Purkinje cells in the cerebellar cortex. The spinal cord was normal. This report describes the first case of PFK deficiency, presenting as a lethal fetal akinesia sequence.     

CD46 (membrane cofactor protein of complement, measles virus receptor): structural and functional divergence among species (review)

OBJECT: In this retrospective study, the authors analyzed the frequency, anatomical distribution, and appearance of traumatic brain lesions in 42 patients in a posttraumatic persistent vegetative state. METHODS: Cerebral magnetic resonance (MR) imaging was used to detect the number of lesions, which ranged from as few as five to as many as 19, with a mean of 11 lesions. In all 42 cases there was evidence on MR imaging of diffuse axonal injury, and injury to the corpus callosum was detected in all patients. The second most common area of diffuse axonal injury involved the dorsolateral aspect of the rostral brainstem (74% of patients). In addition, 65% of these patients exhibited white matter injury in the corona radiata and the frontal and temporal lobes. Lesions to the basal ganglia or thalamus were seen in 52% and 40% of patients, respectively. Magnetic resonance imaging showed some evidence of cortical contusion in 48% of patients in this study; the frontal and temporal lobes were most frequently involved. Injury to the parahippocampal gyrus was detected in 45% of patients; in this subgroup there was an 80% incidence of contralateral peduncular lesions in the midbrain. The most common pattern of injury (74% in this series) was the combination of focal lesions of the corpus callosum and the dorsolateral brainstem. In patients with no evidence of diffuse axonal injury in the upper brainstem (26% in this series), callosal lesions were most often associated with basal ganglia lesions. Lesions of the corona radiata and lobar white matter were equally distributed in patients with or without dorsolateral brainstem injury. Moreover, cortical contusions and thalamic, parahippocampal, and cerebral peduncular lesions were also similarly distributed in both groups. CONCLUSIONS: The data indicate that diffuse axonal injury may be the major form of primary brain damage in the posttraumatic persistent vegetative state. In addition, the authors demonstrated in this study that MR imaging, in conjunction with a precise clinical correlation, may provide useful supportive information for the accurate diagnosis of a persistent vegetative state after traumatic brain injury.     

Merosin-negative congenital muscular dystrophy, occipital epilepsy with periodic spasms and focal cortical dysplasia. Report of three Italian cases in two families

We report clinical, EEG and neuroimaging findings of three patients in two Italian families with merosin-negative congenital muscular dystrophy (CMD), drug-resistant occipital epilepsy, diffuse persistent cerebral white matter changes and focal cortical dysplasia. Clinical and epilepsy histories, EEG and neuroimaging findings were very similar in all patients. Seizures started in childhood and mainly consisted of periodic spasms, a particular type of partial seizure characterized by clusters of epileptic spasms. The motor expression of the spasms was very mild so that they had been frequently missed or misinterpreted as non-convulsive generalized absence seizures. Interictal EEG showed occipital spike-waves and bilateral synchronous slow spike-wave discharges. Ictal EEG showed prolonged periodic sequences of slow waves with associated fast rhythm complexes, characteristic of periodic spasms. Two patients had normal intelligence, one patient presented moderate mental retardation. Focal cortical dysplasia in the posterior areas of the brain, in addition to marked diffuse white matter alterations, was detected in the magnetic resonance images of all patients. Findings in these patients indicate that in merosin-negative CMD brain involvement can include cortical dysplasia, in addition to white matter changes. In such cases the brain damage can lead to a childhood-onset localization-related symptomatic occipital epilepsy. Epileptic seizures and cortical dysplasia can be, however, difficult to detect in CMD. The clinical semiology of epileptic seizures may in fact be modified because of muscular weakness. This implies that epilepsy may be misdiagnosed or even missed and EEG-polymyographic recordings may be necessary to identify it. Similarly, cortical dysplasia may be very localized and visible by neuroimaging only if it is carefully investigated on the basis of epileptological and EEG-polymyographic findings.     

Magnetic resonance in AIDS-related encephalopathy

Fifty-eight patients with AIDS disease were studied with MR imaging in the aim of detecting the grade of brain involvement. The examinations were performed with a 1.5 Tesla magnet. Thirty-seven showed white matter lesion (63.5%), twenty-five patients showed cerebral atrophy (43%), in eight patients the MR appearance was consistent with toxoplasmosis infection (13.5%), two patients showed a linfoma (3.4%) and two patients micrococcosis (3.4%). Seventeen out of the thirty-seven patients with white matter disease showed focal well circumscribed lesion (46%), while twenty showed diffuse involvement. Between the twenty-five patients with cerebral atrophy, twelve showed a prevalence of the cortical involvement and eight a subcortical atrophy. In five patients a concomitant, cortical and subcortical atrophy was found. Between the eight patients with neurotoxolesion and two of them a widespread encephalitis picture. The MR appearance of the two limphomas was that of periventricular, space occupying, masses. In two patients with micrococcis a nodular aspect of leptomeningeal lesions was found.     

Congenital ocular motor apraxia: imaging findings

PURPOSE: To determine the frequency of cerebellar and cerebral abnormalities on brain imaging studies in children with congenital ocular motor apraxia. METHODS: Brain imaging studies were performed in 19 children with typical congenital ocular motor apraxia who were in the care of a visual impairment program at a children's hospital. Independent clinical review categorized the subjects as having partial (n = 10) or expanded (n = 9) congenital ocular motor apraxia on the basis of extent of associated speech or neurodevelopmental problems. Fifteen CT studies and 13 MR examinations of the brain performed in these children were reviewed independently by two pediatric neuroradiologists. Radiologic findings were agreed on by consensus. RESULTS: Cerebellar abnormalities were found in 12 of 19 cases. The cerebellar vermis was small in 10 children. A small cerebellar vermis was the only abnormality in five of 10 children with partial congenital ocular motor apraxia and in two of nine children with expanded congenital ocular motor apraxia. Among seven children with a small vermis examined with high-resolution MR imaging, the inferior portion of the vermis was preferentially involved in each case. Of these seven subjects, none of four with partial congenital ocular motor apraxia but two of three with expanded congenital ocular motor apraxia had an abnormality of the superior portion of the vermis. Miscellaneous supratentorial lesions affecting both gray and white matter were found in six subjects. Five of the 19 children had normal imaging findings. CONCLUSION: Inferior vermian hypoplasia is the most common abnormality in children with congenital ocular motor apraxia.     

MR diffusion imaging in Pelizaeus-Merzbacher disease

A case of classical type Pelizaeus-Merzbacher disease was reported. This patient exhibited marked motor and mental developmental delay, and nystagmus, with a positive familial history. Electrophysiological studies, such as on brainstem auditory evoked potentials, blink reflex and somatosensory evoked potentials, suggested marked disturbance of nerve conduction in CNS. T2-weighted magnetic resonance (MR) images revealed non-progressive diffuse T2 prolongation of cerebral white matter after a 2-year interval, indicating congenital hypomyelination in CNS. A newly developed magnetic resonance diffusion imaging method demonstrated the existence of diffusional anisotropy in the corpus callosum, internal capsule, and white matter of the frontal lobe. Although the diffusional anisotropy was considered to depend on the well-developed multiple layers of myelin around the axons, the imaging data of this patient demonstrated that the diffusional anisotropy did not necessarily depend on those multiple layers. These results may indicate the potential usefulness of MR diffusion imaging, combined with electrophysiological studies and conventional MR imaging, for analyzing the lesions of the cerebral white matter.     

Estrogen and cancellous bone loss in the fowl

Long-term follow-up study with positron emission tomography (PET) has been conducted in a patient with superficial siderosis for ten years. A 63-year-old right-handed woman began to exhibit a cerebellar ataxia when she was 52 years old. Thereafter she has been exhibiting a slowly progressive course of pyramidal signs, hearing loss, anosmia, bilateral sciatica and memory disturbance in addition to the cerebellar ataxia. Series of x-ray CT and MRI disclosed a progressive atrophy of the cerebellum, specifically in the superior vermis, and a mild diffuse atrophy in the cerebral hemispheres, whereas no significant atrophy was seen in the brainstem. A marked hypointensity was seen along the rim of the brain structures including brainstem, cerebellum, sylvian fissures and the medial temporal lobes on MR T 2-weighted images. This hypointensity was also found at the edges of the third and fourth ventricles. These findings were regarded as haemosiderin deposit. By using oxygen-15, PET was carried out repeatedly with ten-year interval. In the initial PET study, both cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were mildly decreased in the cerebellar hemispheres and the occipital cortices. The follow-up PET study revealed a progressive reduction of CMRO2 in the brainstem, cerebellar hemispheres and temporal cortices including the hippocampus in which the haemosiderin deposition was marked on MRI, whereas the reduction of CBF was not advanced as compared with CMRO2. It was suggested that the progressive reduction of CMRO2 in the brain sites where the haemosiderin deposition was observed on MRI reflected the clinical course of neurological deterioration.     

Generation of DNA base modification following treatment of cultured murine keratinocytes with benzoyl peroxide

Imaging findings in two children with molybdenum cofactor deficiency included, in one, diffuse low attenuation on CT in cerebral white matter, caudate nuclei, and thalami soon after birth. MR in both patients later demonstrated progressive widening of the sulci, ventricles, and cisterna magna, and loss of brain volume. MR finally showed cessation of myelination at 31 months and 16 weeks of age.     

MR and cerebrospinal fluid enzymes as sensitive indicators of subclinical cerebral injury after open-heart valve replacement surgery

PURPOSE: To evaluate MR imaging and lumbar cerebrospinal fluid enzymes as potential sensitive indicators of cerebral injury after open-heart valve replacement surgery. METHODS: Thirty-four patients with cardiac valvular disease were prospectively entered into this study and then underwent valve replacement or repair under cardiopulmonary bypass using a membrane oxygenator. In 26 patients, MR head images were obtained 12 to 24 hours before surgery; repeat MR images were obtained between 1 and 2 weeks after surgery. In 18 patients, lumbar puncture cerebrospinal fluid was analyzed 24 to 48 hours after surgery; the analyses included measurement of lactic dehydrogenase, creatine phosphokinase, adenylate kinase, and neuron-specific enolase. RESULTS: After surgery, MR imaging showed new ischemic lesions in 15 (58%) of 26 patients: 7 with deep white matter hyperintense lesions; 5 with brain stem, caudate, cerebellar, or thalamic/basal ganglia infarcts; 1 with intraparenchymal hemorrhage; 1 with a subdural hematoma and cortical infarct; and 1 with a corpus callosum lesion consistent with calcium or air. These new ischemic lesions seen on MR images were associated with a focal neurologic deficit in only 4 (27%) of the 15 patients. Neuron-specific enolase and lactic dehydrogenase were abnormally elevated after surgery in 5 (28%) of 18 patients. Adenylate kinase and creatine phosphokinase (brain isozymes) were elevated in one (67%) of the patients. Two (40%) of the five patients with abnormally high neuron-specific enolase or lactic dehydrogenase after surgery also showed a new focal neurologic deficit. CONCLUSIONS: MR imaging is a sensitive measure of subclinical cerebral ischemia after cardiac valve replacement under cardiopulmonary bypass. Cerebrospinal fluid neuron-specific enolase and lactic dehydrogenase are less sensitive than MR imaging for detecting subclinical cerebral ischemia, but these values were elevated after surgery more frequently than was adenylate kinase in our patients.     

Expression of functional tissue factor on small vesicles of lipopolysaccharide-stimulated human vascular endothelial cells

An autopsy case of Sj?gren-Larsson syndrome (SLS), an 8-year-old boy, is presented with neuropathological investigations. Widespread deposition of 2 different types of unusual substances, stained lightly or strongly with periodic acid Schiff (PAS) was most conspicuous in this case. The first type of them, lightly stained with PAS at room temperature, was widely distributed in the central nervous system (CNS): the white matter of cerebrum and brainstem, subpial and subependymal glial layers, subpial space, perivascular space of small blood vessels, and their adjacent nervous tissue. The second type, strongly stained with PAS, small round or ellipsoid bodies, was found in the subpial, subependymal and perivascular glial layers. The first type of PAS-positive substances might be fatty alcohols or their metabolites, and the second type, some degraded products of lipids in astrocytic processes. Lipofuscin-like substances were accumulated in perivascular macrophages located around small blood vessels. Spheroid bodies (axonal swellings) were frequently observed in relay nuclei: lateral geniculate body (LGB), pontine nuclei, inferior olivary nuclei, posterior funicular nuclei, or cerebellar dentate nuclei. A lot of PAS-positive fine granules were contained in a spheroid body of LGB. Scarcity of myelinated nerve fibers was recognized in the cerebral and cerebellar white matter and the corticospinal tracts of spinal cord. Focal cortical dysgenesis, resembling that of unlayered polymicrogyria, was observed in bilateral insular cortices. Further histochemical studies are needed to explore the exact pathogenesis, but widespread deposition of PAS-positive substances in CNS may support the supposition that SLS is one of congenital errors of lipid metabolism.     

Reducing costs through case management

Ultrasound dopplerography, MR tomography were performed to assess the brain, major cerebral arteries and audiometry was conducted to study cochleovestibular system in 38 patients aged 16-63 years with heterozygous family hypercholesterolemia. Vascular disorders and defects in the white brain matter (in patients with transitory hypertension) were registered. Complications of cerebral atherosclerosis (brain infarction, perception cochleovestibular alterations) contributed to aggravation of ischemic heart disease. Patients with heterozygous family hypercholesterolemia should be observed and treated by cardiologist, neuropathologist and psychoneurologist to prevent cardiocerebral complications.     

A particular type of epilepsy in patients with congenital hemiparesis associated with polymicrogyria or unilateral pachygyria

INTRODUCTION: Magnetic resonance has permitted the recognition of cortical dysplasias in patients with congenital hemiparesia and epilepsy. OBJECTIVE: To study the clinic-EEG characteristics and course of epilepsy in patients with congenital hemiparesia and unilateral polymicrogyria. METHODS AND RESULTS: We analyzed the clinical histories of 11 patients seen between 1990 and 1996. We studied 6 girls and 5 boys aged between 5 and 13 years, with a follow-up period of from 1 to 6 years. The epilepsy began at between 1 and 6 years old with partial motor seizures. On EEG there were frontotemporal spikes in 9 cases, temporooccipital in 1 and parieto-occipital in another. All 11 patients had hemiparesia, with slight mental retardation in 9 patients and moderate mental retardation in 2. The CT/MR brain scan showed unilateral polymicrogyria. At between 2 and 8 years of age, all 11 patients developed subintrant atonic crises with a pseudo-ataxic gait, absences in 7 patients and myoclonia in 3. Awake EEG showed bilateral asymmetrical spikes. During sleep 7 patients had continuous spikewave discharges and 4 had frequent asymmetrical bilateral spikes. Four patients relapsed. Five patients are free of crises, five have sporadic crises and one continues to have daily crises. CONCLUSIONS: These patients had hemiparetic cerebral paralysis, slight mental retardation and epilepsy. At about the age of 6 a peculiar electro-clinical condition developed. Response to treatment was satisfactory, although the follow-up period is still not long.     

MR findings in pontocerebellar hypoplasia

We present four cases with combined hypoplasia of the cerebellum and the ventral pons-pontocerebellar hypoplasia (PCH). PCH represents an autosomal recessive neurodegenerative disorder with fetal onset. The disease is rare, with less than 20 cases having been reported. The main findings of PCH and the inclusion criteria for our cases can be summarised as progressive microcephaly from birth, pontocerebellar hypoplasia documented by MRI and marked chorea, which may change, later in childhood, to more dystonic patterns. The cerebral cortex becomes progressively atrophic. Motor and mental development are delayed, and epilepsy, mainly tonic-clonic seizures, is frequent. The MRI features in all of our cases were: (1) Hypoplastic cerebellum situated close to the tentorium. The hypoplastic cerebellum has a reduced number of folia, in contrast to the normal number of thin folia in simple cerebellar atrophy. (2) The cerebellar hemispheres are reduced to bean-like or wing-like structures. The cerebellar hemispheres appear to 'float' in the posterior fossa. (3) Markedly hypoplastic ventral pons. (4) Slight atrophy of the supratentorial gyral pattern. (5) Dilated cerebromedullary cistern and fourth ventricle. (6) Delayed myelination of the white matter. (7) No significant disorganisation of brain architecture and no severe corpus callosum defect.