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Clinical analysis of West syndrome associated with phenylketonuria.

OBJECTIVE: To explore the incidence and clinical characteristics of West syndrome associated with phenylketonuria (WS-PKU) and significance of early combination therapy of low phenylalanine (PHE) diet and anticonvulsants (antiepileptic drugs, AEDs) in WS-PKU. SUBJECTS AND METHODS: Sixty-two WS-PKU patients (41 boys and 21 girls) out of 503 PKU patients were enrolled in the study. Age at PKU diagnosis varied from 4 months to 7 years old. Serum PHE levels were 20-38.5mg/dl. In the majority of cases, infantile spasms (IS) became manifest first preceding the PKU diagnosis, except eight cases in which spasms appeared after starting the diet therapy. All patients were subjected to mental and electroencephalographic (EEG) examination. Brain myelination was evaluated by using brain magnetic resonance imaging (MRI) with Staudt's standard. RESULTS: WS-PKU patients accounted for 12.3% of PKU patients. No patients who were given low PHE diet before age 3 months suffered from WS, whereas 17 out of 156 patients who started the diet between age 4 and 12 months developed WS later (10.9%), and similarly, 45 out of 283 patients who started the diet after 12 months of age developed WS later (15.9%). Moderate and severe mental retardation were noted in 58.8% of patients who received the diet before age 1 and in 84.4% of those after age 1 (P<0.05). EEG displayed hypsarrhythmia and diffuse background abnormality. MRI scans showed delayed myelination mainly in the cerebral lobes and corpus callosum and abnormal high T(2)-signal intensity (100%) in the periventricular region around anterior and posterior horns of both lateral ventricles. With the start of diet, spasms began to decrease its frequency, but relapsed frequently (78%) when no AEDs were given. Seizure relapse was significantly lower when valproic acid or nitrazepam were given concomitantly with the diet (18.2%). CONCLUSIONS: IS often occurred as the initial clinical sign of PKU. Early diagnosis of PKU and early therapy with low PHE diet seem to be highly effective in preventing WS.

Brain↗

Potential of diffusion imaging in brain tumors: a review.

Diffusion magnetic resonance imaging (MRI) is a method for quantifying the microscopic random motion of water molecules in tissues. Diffusion imaging provides indirect structural information of a kind not available on basic MRI sequences of many pathological conditions. Lately, especially brain tumors have been under active investigation, with numerous papers already published, and their number continues to increase. This review summarizes the heterogeneous and complex research data on diffusion imaging of brain tumors.

Astrocytoma↗

Niemann-Pick disease type C (a cellular cholesterol lipidosis) treated by bone marrow transplantation.

Bone marrow transplantation (BMT) has been used for a wide variety of lysosomal storage diseases with encouraging results. We report a 3-year 5-month-old girl with Niemann-Pick type C disease (NPC) who received an allogeneic BMT. The patient presented with repeated lower respiratory tract infections, hepatosplenomegaly, failure to thrive, and developmental delay. Chest computed tomography (CT) revealed diffuse interstitial lung infiltration. Bone marrow and liver biopsies revealed abundant lipid-filled foamy macrophages. Skin fibroblast sphingomyelinase assay revealed partial deficiency. The ability of her skin fibroblasts to esterify cholesterol was very low, and the cells stained brightly for free cholesterol. She received BMT from a healthy HLA-identical male sibling donor at the age of 2 year 6 months. Full engraftment was evidenced by repeated bone marrow sex chromosome studies. Regression of the hepatosplenomegaly, markedly reduced foamy macrophage infiltration in bone marrow, and decreased interstitial lung infiltration was noted 6 months after BMT. Her neurological status, however, deteriorated. Follow-up magnetic resonance image (MRI) revealed progressive, diffuse brain atrophy. We conclude that resolution occurred in the liver, spleen, bone marrow and lung following successful engraftment. Such a response is remarkable since the underlying problem involves a membrane receptor for cholesterol. This positive response might be due to replacement of the monocyte-phagocytic system or it may imply the existence of cross-correction in the NPC membrane receptor defect by BMT approach. Since BMT did not halt the neurological deterioration, it is unlikely to be an adequate treatment for NPC.

Bone Marrow Transplantation↗

Cerebral emboli during left heart catheterization may cause acute brain injury.

AIMS: Left heart catheterization carries a risk for cerebral complications. The aims of this prospective study were to determine the frequency and composition of catheterization-related cerebral microemboli and to detect cerebral morphological changes and acute cognitive impairment due to catheterization. METHODS AND RESULTS: Forty-seven unselected patients undergoing elective left heart catheterization, either by transradial or by transfemoral access, were monitored for cerebral microemboli using multifrequency transcranial Doppler. Cerebral magnetic resonance imaging (MRI) with diffusion-weighted imaging sequences and neuropsychological assessments were carried out on the day before and the day after catheterization. A median number of 754 cerebral microemboli were detected: 92.1% were gaseous and 7.9% were solid. New cerebral lesions were observed in 15.2% of the transradial, but none of the transfemoral, catheterization patients (P=0.567). These lesions were significantly associated with a higher number of solid microemboli (P=0.016) and a longer fluoroscopy time (P=0.039). There was also a significantly higher number of solid microemboli during transradial than during transfemoral catheterization (P=0.012). Cognitive impairment following the investigations was associated with the degree of pre-catheterization cerebral MRI injury (P=0.03). CONCLUSION: During left heart catheterization, cerebral microemboli, especially those which are solid, may damage the brain. Cardiac catheterization may therefore pose a greater risk for the brain than previously acknowledged.

Aged↗

The ischemic penumbra: a new opportunity for neuroprotection.

The development of acute stroke therapies has yielded only limited success and many failures in multiple clinical trials. The target of acute stroke therapy is that portion of the ischemic region that is still potentially salvageable, i.e. the ischemic penumbra. Neuroprotective drugs have the potential to prevent a portion of the ischemic penumbra from evolving into infracted tissue and designing trials that target neuroprotective drugs at patients with persistent penumbra should enhance the likelihood of a positive outcome. Currently, diffusion and perfusion MRI has the potential to approximate the location and persistence of the ischemic penumbra and can be used in clinical trials to select appropriate patients for inclusion and to evaluate a meaningful treatment effect. Perfusion CT may also have similar capabilities. Use of these imaging modalities in clinical trials and ultimately in clinical practice will likely help in the development and utilization of novel neuroprotective drugs.

Animals↗

Water household of the common carp, Cyprinus carpio, when submitted to an osmotic challenge, as determined by diffusion-weighted magnetic resonance imaging at 7 T.

In vivo diffusion-weighted magnetic resonance imaging (MRI) was used to determine the effects of an osmotic challenge (1% NaCl) to a freshwater fish, the common carp (Cyprinus carpio). The imaged region covered organs such as the swimbladder, the liver, the kidney, the intestine, the spinal cord, and muscle tissue. A striking difference between salt-treated and control fish was found in the liver. The apparent diffusion coefficient value of livers from control fish was (0.39 +/- 0.16) 10(-9) m2/s and of salt-treated fish was (1.23 +/- 0.14) 10(-9) m2/s, which points to an increase in extracellular water content. These results were partially confirmed by a decrease in dry/wet weight ratio of the liver tissue. We also found increased levels of stress proteins in liver tissue. The Q factor of the applied radiofrequency coil dropped dramatically when we performed experiments with salt-exposed fish, indicating an increased conductivity resulting from the increased ion concentration and osmolarity of the fish. The data on plasma osmolarity of salt-exposed fish confirm a significant osmolarity increase upon salt exposure (from 334 to 430 mOsm/kg) and exceeded the osmolarity of the salt water (324 mOsm/kg), indicating that carp tend to cope with an increased salinity by increasing the internal osmolarity (hyperosmotic regulation). These data demonstrate that diffusion-weighted MRI might be a useful and noninvasive tool in the study of osmotic challenges of aquatic organisms.

Animals↗

The importance of magnetic resonance imaging in the diagnosis and treatment of diffuse lymphangioma.

In this study, we will investigate the importance of MRI in the diagnosis and treatment of diffuse lymphangioma. Twenty-nine patients with lymphangiomas were treated at the U.Z. Leuven between March 1988 and September 1997. They all underwent a total surgical excision of the lesion. A global recurrence rate of 34.45% corresponds with a recurrence rate of 30.76% found in literature. In our study, a remarkable difference in recurrence rates is noticed between cystic hygroma (5/19 patients or 26.39%) and the more diffuse types of lymphangioma (5/10 patients or 50%). On three patients, preoperative MRI was performed. All these illustrate the important role of MRI in the diagnosis of lymphangioma, namely the characteristic appearance of the lesions on T1- and T2-weighted images and the better visualization of the lymphangioma extent. In line with the high recurrence rates of diffuse lymphangiomas and the advantages of MRI of these lesions, the role of MRI in the treatment of diffuse lymphangiomas is discussed.

Adolescent↗

Bone marrow metastasis of neuroblastoma analyzed by MRI and its influence on prognosis.

Bone marrow metastases (BM mets) of neuroblastoma were analyzed by magnetic resonance imaging (MRI). BM mets were demonstrated in 45 femurs of 23 patients with neuroblastoma by MRI. They were classified into two patterns, nodular (N) type and diffuse (D) type, on MRI, with an incidence of 16% (7/45) and 84% (38/45), respectively. No bone metastases (B mets) were accompanied by N type BM mets, whereas all of them were accompanied by D type BM mets. The rate of disappearance of N type BM mets after chemotherapy was 100% (7/7) and was significantly higher than that (26%, 10/38) of D type BM mets. The rate of disappearance (58%, 11/19) of BM mets in bones without associated B mets was also significantly higher than that (23%, 6/26) of BM mets in bones with associated B mets. BM mets present in bones with B mets tended to persist after chemotherapy. The survival rate of patients with residual BM mets after chemotherapy was significantly lower than that of patients without residual BM mets. This suggests that powerful systematic chemotherapy and additional targeted therapy to lesions remaining after chemotherapy are needed to improve the cure rate of patients with advanced neuroblastoma.

Bone Marrow↗

Trimethoprim and sulfonamide-associated meningoencephalitis with MRI correlates.

Early recognition of trimethoprim and sulfonamide-induced aseptic meningitis is important because drug cessation leads to rapid clinical improvement. We present clinical and laboratory findings in two typical cases. In both cases, MRI revealed previously undescribed diffuse white matter abnormalities that resolved within a few months. These MRI findings are important because they may aid in early diagnosis of this condition in the appropriate clinical setting. In addition, the white matter abnormalities suggest an encephalitic component in addition to the meningitis.

Adult↗

Microvascular basal lamina damage in thromboembolic stroke in a rat model.

We investigated microvascular damage in areas with magnetic resonance imaging (MRI)-defined apparent diffusion coefficient reduction (ADC-R) in a rat model of thromboembolic occlusion of the middle cerebral artery. Rats received either intracarotid recombinant tissue plasminogen activator (rt-PA) or saline. Microvascular basal lamina damage was quantified by immunohistochemical staining of collagen type IV and by videoimaging analysis. ADC-R positive basal ganglia (cortical) areas showed a significant reduction of stained microvascular area by 15+/-6% (8+/-7%) and the microvascular density by 13+/-5% (8+/-6%) of that on the non-ischemic control side (P<0.001). There were no significant microvascular differences between rats given rt-PA or saline, or between those with or without angiographically proven recanalization. This study reports for the first time that microvascular basal lamina damage in experimental thromboembolic stroke is confined to regions with ADC-R in MRI.

Angiography↗

[An infant with diffuse axonal injury].

Development of MRI enabled accurate and rapid diagnosis of head traumas which had been impossible with the conventional CT. The diagnosis of posttraumatic diffuse axonal injury (DAI) is a typical example. Most of the reported cases of DAI in childhood are of relatively older age, and DAI is rare in infancy. We report here a 1-year-9-month-old infant with DAI. After falling from two meters in height, he presented consciousness disturbance and a seizure that necessitated artificial respiration for half a day. He recovered completely without sequelae. Brain CT on arrival to the ER department was unremarkable, but MRI scans shortly thereafter showed typical findings of DAI. In childhood, DAI tends to be milder than in adult-hood, which may be explained by the age-dependent frequency of traffic accidents, and by anatomical and functional factors of a infant's brain. A large number of infantile cases should be accumulated to draw a more clearcut conclusion.

Brain↗

[Long-term fate of left atrial thrombi and incidence of cerebral embolism under continuous anticoagulation therapy].

PURPOSE: Patients (pts.) with atrial fibrillation (AF) and atrial thrombi are known to have an increased risk for cerebral embolism. However, little is known about the clinical course of atrial thrombi and the incidence of cerebral embolism in those patients during anticoagulation therapy. The high sensitivity of MR imaging (MRI) including diffusion-weighted imaging (DWI) suggests that this technique could provide an improved estimate of cerebral embolism associated with the presence of left atrial thrombi. The aims of this prospective study were to evaluate 1) the prevalence of clinically silent and apparent cerebral embolism in pts. with newly diagnosed AF and atrial thrombi using MRI/DWI, 2) the long-term fate of atrial thrombi under continues anticoagulation therapy and 3) the incidence of cerebral embolism during a follow-up period of 12 months with continuous anticoagulation therapy. MATERIALS AND METHODS: The study group consisted of 32 pts. with 1) newly diagnosed AF and evidence of left atrial (LA) thrombi detected by TEE and 2) a new start of anticoagulation therapy [International Normalized Ratio (INR) 2.0 - 3.0]. 19 pts. with 1) newly diagnosed AF and no evidence of atrial thrombi and 2) an equivalent anticoagulation regimen served as the control group. In both groups a) MRI/DWI studies of the brain (weeks 0, 4, 8, 12, 20, 28, 36, 44, and 52), b) transesophageal echocardiographic studies (TEE) for assessment of LA-Thrombi (weeks 0 and 52) and c) clinical neurological assessments (weeks 0, 20 and 52) were performed. RESULTS: In the study group (AF and LA-Thrombi) 11 out of 32 pts. (34 %) displayed signs of acute (n = 8) or chronic (n = 3) cerebral embolism in the initial MRI studies. In 4 out of 32 pts. (13 %), MRI/DWI depicted new or additional cerebral emboli (n = 12) during the follow-up period despite continuous anticoagulation therapy. 2 (n = 2/4; 50 %) of these patients had clinically apparent neurological deficits. In the control group 1 out of 19 pts. (5 %) showed evidence of chronic cerebral embolism as assessed by MRI/DWI at the beginning of the study (week 0). No embolic cerebral lesions were detected during the 12-month follow-up. Within 12 months only 63 % (n = 20/32) of LA thrombi in the study group resolved completely under anticoagulation. CONCLUSION: 1. The incidence of clinically inapparent cerebral emboli in pts. with newly diagnosed AF and atrial thrombi is much higher than the incidence of clinically apparent emboli and has been underestimated in the past. 2. New cerebral embolism may occur even with continued effective anticoagulation therapy in 13 % of pts. 3. Only 63 % of atrial thrombi resolve completely within 12 months under anticoagulation therapy.

Aged↗

Delayed neuroprotective effect of insulin-like growth factor-i after experimental transient focal cerebral ischemia monitored with mri.

BACKGROUND AND PURPOSE: Insulin-like growth factor (IGF) treatment has been shown to have trophic and neuroprotective effects in vitro and in vivo in different lesion models. IGF-I has potent neuroprotective effects after hypoxic-ischemic injury and global ischemia. The role of IGF-I in focal cerebral ischemia is only partially understood. Therefore, in the present study, we evaluated, by applying MRI monitoring, whether a clinically relevant systemic administration of IGF-I can achieve a long-lasting neuroprotective effect. METHODS: Male Wistar rats underwent transient occlusion of the right middle cerebral artery for 1 hour by using the suture occlusion model. Animals then were intraventricularly treated with 33.33 microg IGF-I/d for 3 days (group A, the IGF-I group [n=13]; group B, the placebo group [n=14]) or subcutaneously treated with 200 microg IGF-I/d for 7 days (group D, the IGF-I group [n=10]; group E, the placebo group [n=10]). Groups C and F served as sham-operated controls (n=5 and n=3, respectively). Treatment was begun 30 minutes after occlusion of the middle cerebral artery. Subcutaneously treated animals underwent MRI studies (diffusion-weighted imaging, perfusion imaging, and T2-weighted imaging) beginning 60 minutes after vessel occlusion at 6 hours and at days 1, 2, 5, and 7 after ischemia. The animals were weighed and neurologically assessed daily (rating scale ranged from 0, indicating no deficit, to 5, indicating death). On the third day (intraventricular trial) and on the seventh day (subcutaneous trial), animals were euthanized, and brain sections were stained with triphenyltetrazolium chloride. RESULTS: The mean infarct volume was 52.9+/-25.2 mm(3) in intraventricularly treated animals versus 146.4+/-62.2 mm(3) in control animals (P<0.01) and 42.2+/-17.9 mm(3) in subcutaneously IGF-I-treated animals versus 73.1+/-38.1 mm(3) in control animals (P<0.05). Apparent diffusion coefficient-derived lesion volume at 60 minutes after occlusion was 40.4+/-23.7 mm(3) versus 38.3+/-19.3 mm(3) (P=NS), increased to 168.3+/-49.55 mm(3) versus 105.5+/-33.8 mm(3) (P<0.05) at 24 hours, and then decreased to 55.8+/-30.3 mm(3) versus 23.3+/-20.2 mm(3) (P<0.05) for control and IGF-I-treated animals, respectively. The T2-weighted-derived ischemic lesion volume at 24 hours after occlusion was 236+/-49.2 mm(3) versus 115.9+/-56.8 mm(3) (P<0.05) and decreased to 115.9+/-26.2 mm(3) versus 75.7+/-35.8 mm(3) (P<0.05) at day 7 for control and IGF-I-treated animals, respectively. The relative regional cerebral blood volume was reduced to 50% before reperfusion in all regions of interest except for region of interest 1 (vessel territory of anterior cerebral artery), recovered during reperfusion, but was not different between the control and the growth factor-treated group at any imaging time point. There was no significant difference in weight loss. There was less neurological deficit after ischemia in intraventricularly and subcutaneously IGF-I-treated animals compared with control animals (P<0.05). CONCLUSIONS: Continuous treatment with intraventricularly and subcutaneously administered IGF-I achieved a long-lasting neuroprotective effect as early as 24 hours after ischemia as measured by MRI. Therefore, IGF-I may represent a new approach to the treatment of focal cerebral ischemia.

Animals↗

Cortical projections to the human red nucleus: a diffusion tensor tractography study with a 1.5-T MRI machine.

INTRODUCTION: Previous studies in apes and monkeys have shown that the red nucleus receives projections from the sensorimotor and premotor cortices, whereas other experiments carried out with injured human brains have found corticorubral projections issuing from associative areas. Therefore, we reassessed in vivo the human anatomical projections from the cerebral cortex to the red nucleus using diffusion tensor imaging (DTI) axonal tracking. METHODS: The connectivity between the cerebral cortex and the red nuclei of seven volunteers was studied at 1.5 T using streamlined DTI axonal tracking. RESULTS: Trajectories were constantly tracked between the red nuclei and the ipsilateral pericentral and prefrontal cortices, as well as the temporal cortex and the striatum in two subjects. Within the cerebral trunk, trajectories also include the superior cerebellar peduncle and the central tegmental tract. CONCLUSION: The human red nucleus receives its main afferences from the sensorimotor and prefrontal cortices.

Adult↗

Pyramidal tract lesions and movement-associated cortical recruitment in patients with MS.

Cortical functional changes, with the potential to limit the functional consequences of tissue injury, have been shown in patients with multiple sclerosis (MS). In this study, we assessed the influence of MS-related tissue damage of the brain portion of the left pyramidal tract on the corresponding movement-associated patterns of cortical recruitment in a large sample of MS patients when performing a simple motor task with their fully normal functioning right upper limbs. We investigated 76 right-handed patients with definite MS. In each subject, functional magnetic resonance imaging (fMRI) was acquired during the performance of a simple motor task with the dominant, right upper limb. During the same session, dual-echo, magnetization transfer (MT) and diffusion tensor (DT) MRI sequences were also obtained to quantify the extent and the severity of pyramidal tract damage. Lesions along the left pyramidal tract were identified in 43 patients. Compared to patients without pyramidal tract lesions, patients with such lesions had more significant activations of the contralateral primary sensorimotor cortex (SMC), secondary sensorimotor cortex (SII), inferior central sulcus, and cingulate motor area (CMA). They also showed more significant activations of several regions of the ipsilateral hemisphere, including the primary SMC and the precuneus. In these patients, T2 lesion load of left pyramidal tract was correlated with the extent of activation of the contralateral primary SMC (r2 = 0.25, P < 0.0001), whereas no correlations were found between the extent of fMRI activations and the severity of intrinsic lesion damage, as well as with left pyramidal tract normal-appearing white matter damage. This study shows that, in patients with MS, following injury of the motor pathways, there is an increased recruitment of a widespread sensorimotor network, which is likely to contribute to limit the appearance of overt clinical deficits.

Adult↗

Electrophysiological brainstem testing in the diagnosis of reversible brainstem ischemia.

The aim of this study was to evaluate the sensitivity of multimodal electrophysiological brainstem testing in the diagnosis of clinically suspected reversible ischemic deficits of the brainstem compared with diffusion weighted MR imaging. We investigated 158 consecutive patients presenting with signs of acute brainstem dysfunction. Serial electrophysiological brainstem tests including masseter reflex, blink reflex, masseter inhibitory reflex, AEP, MEP, EOG and the oculoauricular phenomenon were applied. In 14 of the 158 patients neurological deficits resolved in less than 24 hours, which was suggestive of a transitory ischemic attack (TIA), 19 patients had brainstem signs for more than 24 hours but less than 1 week, suggestive of a reversible ischemic neurological deficit (RIND). Electrophysiological data indicated acute functional brainstem lesions in 54,5 % of patients with transient clinical brainstem impairment. Lesion detection rate was significantly higher when combining electrophysiological data and MRI (60,4 %) than using acute brainstem abnormalities in diffusion weighted MRI alone (39,4 %). We conclude that diffusion weighted MRI and electrophysiological brainstem testing are complimentary sensitive indicators of acute brainstem lesions in patients with reversible neurological deficits. Correct identification of brainstem ischemia influences the therapeutic regimen and may improve patient outcome.

Adult↗

MRI analysis of the changes in apparent water diffusion coefficient, T(2) relaxation time, and cerebral blood flow and volume in the temporal evolution of cerebral infarction following permanent middle cerebral artery occlusion in rats.

Detailed knowledge of similarities and differences between animal models and human stroke is decisive for selecting clinically effective drugs based on efficacy data obtained preclinically. Differences in the temporal evolution of stroke pathologies between animal models and man have been reported. In view of the importance of this issue for the development of neuroprotective treatments, the temporal evolution of stroke pathologies in the rat permanent middle cerebral artery occlusion (pMCAO) model has been evaluated with magnetic resonance imaging modalities under experimental conditions matching as close as possible those used in humans. Changes in the ipsilateral and contralateral cortex and striatum of cerebral blood flow (CBF) and volume (CBV), apparent diffusion coefficient (ADC), and spin-spin relaxation time (T(2)), as well as total cortical and striatal infarct volumes, calculated from CBF, ADC, and T(2) maps, were determined starting 1 h up to 216 h post-pMCAO. The temporal evolution of the MRI parameters in this rat model was similar to that observed in humans. In particular, the ADC values were decreased for more than 3 days and returned back to baseline between 4 to 8 days, to increase by day 9 only. Thus the stroke pathology in this rat model develops at a similar pace as in stroke patients arguing against a fundamental difference in the mechanisms involved. The infarct volumes however develop differently in this rat model as they invariably increase over the first 48 h, while in humans the evolution of infarct volume is slower and more heterogeneous.

Animals↗

Diffusion tensor imaging: concepts and applications.

The success of diffusion magnetic resonance imaging (MRI) is deeply rooted in the powerful concept that during their random, diffusion-driven displacements molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. As diffusion is truly a three-dimensional process, molecular mobility in tissues may be anisotropic, as in brain white matter. With diffusion tensor imaging (DTI), diffusion anisotropy effects can be fully extracted, characterized, and exploited, providing even more exquisite details on tissue microstructure. The most advanced application is certainly that of fiber tracking in the brain, which, in combination with functional MRI, might open a window on the important issue of connectivity. DTI has also been used to demonstrate subtle abnormalities in a variety of diseases (including stroke, multiple sclerosis, dyslexia, and schizophrenia) and is currently becoming part of many routine clinical protocols. The aim of this article is to review the concepts behind DTI and to present potential applications.

Brain Diseases↗