Cerebral Basal Ganglia Research Articles

Severe Cerebral Calcification in a Case of LEOPARD Syndrome

We report severe brain calcification in a case of LEOPARD syndrome that has not been reported in the literature. A 53-year-old Japanese man presented with generalized lentigines, arrhythmia, gonadal hypoplasia, endocrine abnormality, mental retardation and skeletal abnormalities, and was consequently diagnosed as LEOPARD syndrome. Brain computed tomography demonstrated surprisingly dense and symmetric calcifications in the cerebellar dentate nuclei, cerebral basal ganglia, thalamus, and cerebral white matter. It may be an incidental idiopathic calcification. Alternatively it may be a rare clinical manifestation of LEOPARD syndrome.

Expression mapping of cytotoxic T-lymphocyte antigen-2α gene transcripts in mouse brain

Cytotoxic T-lymphocyte antigen-2alpha (CTLA-2alpha), an inhibitor peptide homologous to the proregion of mouse cathepsin L, was originally discovered and expressed in mouse-activated T-cells and mast cells. Expressed recombinant CTLA-2alpha is shown to exhibit selective inhibition to cathepsin L-like cysteine proteinases. However, its in vivo targets in mammalian tissues are yet to be identified. We carried out in situ hybridization studies to examine the expression pattern of CTLA-2alpha mRNA and determine the specific cell types synthesizing CTLA-2alpha in the mouse brain. CTLA-2alpha mRNA was detected in various neuronal populations within the telencephalon in cerebral cortices, olfactory system, septum, basal ganglia, amygdala and highest levels were observed in the hippocampus. Within the diencephalon high density of positive cells was found in mediodorsal and lateral posterior thalamic nuclei and medial habenular nucleus (MHb). In the hypothalamus, high density of CTLA-2alpha mRNA labeling was seen in the suprachiasmatic nucleus (Sch), optic tract, arcuate nucleus, and median eminence. The fasciculus retroflexus and its termination in the mesencephalic interpeduncular nucleus were also densely labeled. Other mesencephalic expression sites were the superior colliculus, periaqueductal gray, paramedian raphe nucleus, and inferior colliculus. In the rhombencephalon, strong labeling was detected in the pontine, vestibular, and reticular nuclei. Intense expression was also noted within cerebellar cortex in Purkinje neurons and at a moderate level in granule cell layer, stellate, and basket cells. A possible function of this novel inhibitor peptide in relation to learning, memory, and diseases is discussed.

Positron Emission Tomography in Rasmussen’s Encephalitis

This report presents unusual positron emission tomography findings in an 11-year-old male with Rasmussen's encephalitis. This patient underwent fluorine-18 fluorodeoxyglucose positron emission tomography to localize his ictal focus before surgical consideration. Positron emission tomography disclosed marked hypermetabolism in the left cerebral hemisphere and basal ganglia with subnormal right cerebral activity and crossed cerebellar diaschisis. The heterogeneous distribution of metabolism suggests a combination of areas in different stages of ictal and postictal involvement. The hypermetabolic region in the left hemisphere was larger in size and extent (now including the left frontoparietal lobe) than the sole hypermetabolic left temporal lobe on his positron emission tomography from 2 years ago. While this positron emission tomography pattern of progression appears most commonly in Rasmussen's encephalitis case studies, few serial reports exist. The complex positron emission tomography findings of this case emphasize the importance of knowing the history of recent seizures, seizure type, clinical status at time of injection, and electroencephalographic correlation before interpreting functional neuroimaging studies. Finally, positron emission tomography studies can help clarify whether patients with Rasmussen's encephalitis with dominant hemisphere involvement are appropriate candidates for surgery or not.

Forebrain dopamine receptors in cognitive, memory and learning processes

Neurons that utilize dopamine (DA) as a neurotransmitter have attracted great interest because of their involvement in the behavioral, endocrine and descending control of major brain functions. DA is known to exert its physiological effects on target neurons through D1-like (D1 and D5) and D2-like (D2, D3 and D4) receptor subtypes. To better understand the DA modulation of brain functions, the distribution and cellular localization of D1 and D2 DA receptors in the rat forebrain is reviewed, and their possible role in cognitive aspects of behavior is discussed. In general, DA receptors are differentially expressed and mostly distributed in different target fields of DA neurons. Both D1 and D2 receptor gene products are found in the cerebral cortex, basal ganglia and hippocampal formation, albeit in different cell groups or neuronal subpopulations, whereas D3 receptors are mainly located in limbic regions. In the cortex, mRNA signals are seen in all the areas and cortical layers except layer I. In the striatum, the most intense signal is found in the caudate-putamen, nucleus accumbens and olfactory tubercle where a large number of cells are strongly labeled for D1 and D2. In the globus pallidus only scattered D2 mRNA-containing cells are present. In contrast, no D1 or D2 messages can be seen in the ventral pallidum. In the basal forebrain, mRNA encoding the D1 receptor is detected in the islands of Calleja. The medial and lateral septal nuclei show a low D2 signal. In the amygdaloid nuclear complex, the strongest D1 receptor message is observed in the basomedial and basolateral nuclei. Conversely, the highest density of D2 mRNA-expressing cells is revealed in the central nucleus. Moderately labeled for D1 and D2 cells are scattered throughout the anterior and posterior subdivisions of the bed nucleus of stria terminalis, and within all subfields of the hippocampal formation and dentate granule cell layer. Differential regional and cellular distribution of DA receptors in the forebrain provides anatomical evidence for an area-specific regulation of the DAergic neurotransmission. It can be inferred that DA facilitates learning, memory and cognition processes via activation of both the D1 and D2 receptors. Biomedical Reviews 2005; 16: 59-75.

Cerebral Lipiodol Embolism After Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma

A case of cerebral lipiodol embolism after transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma is presented. A 76-year-old man underwent TACE for advanced hepatocellular carcinoma. Immediately after chemoembolization, his level of consciousness deteriorated. Computed tomography revealed deposition of iodized oil in the cerebral cortex, basal ganglia, and thalami. Magnetic resonance imaging showed restricted diffusion within the thalami and basal ganglia. The patient's level of consciousness gradually improved, and all neurologic symptoms disappeared over 6 weeks.

Functional studies of the human auditory pathway after monaural stimulation with pure tones. Establishing a normal database

ConclusionsBilateral activation of Brodmann area 39 provides functional support for the concept of bilateral cortical activation with auditory stimulation. The observation that when Brodmann area 39 is activated, area 38 of the temporal lobe is simultaneously inhibited (a functional observation that has seemingly not been previously reported) supports the concept that inhibitory as well as excitatory relays play a role in the auditory pathways. In addition, this report helps to establish a functional database for future studies.Objectives(i) To determine which areas of the cerebral cortex and basal ganglia are activated when the left and right ears are monaurally stimulated with pure tones, and what type of response (e.g. excitatory or inhibitory) occurs in these different areas. (ii) To determine the degree of ipsi- and/or contralateral cortical activation and/or inhibition depending on the ear that is stimulated. (iii) To use this information as an initial step to develop a normal functional database for future studies.Material and methodsA brain perfusion single-photon emission CT (SPECT) evaluation was conducted using auditory monaural stimulation with pure tones in 10 normal volunteers. Both ears were tested independently (20 examinations in total). 99mTc hexamethyl-propylenamine-oxime was injected while pure tones were delivered, and the SPECT imaging was done 1 h later.ResultsAfter delivering pure tones there was bilateral cortical activation in Brodmann areas 39 and 40, regardless of which ear was stimulated. Despite marked hyperperfusion in both areas 39, a more intense response was seen on the left compared to the right side, although this was not statistically significant. There was also activation in the executive frontal cortex areas 9 and 10 as well as in the temporal Brodmann areas 21 and 22. Simultaneously, area 38 of the temporal lobe was deactivated. In the subcortical structures there was also marked activation in both thalami and deactivation of the caudate nuclei without lateralization.

A 35-year-old female with growth and developmental retardation, progressive ataxia, dementia and visual loss

This female patient was born to healthy parents who were first cousins. Her elder brother and two paternal uncles had a disorder similar to hers. She began to walk at the age of 1 years and 6 months. During childhood, she was physically small and mentally retarded. To receive special education, she went to school on foot. Gait ataxia appeared at the age of 19 years, and gradually worsened thereafter. When she was 31 years of age, she became unable to walk unsupported. She showed progressive loss of vision and hearing, spoke fewer words than previously, and complained of fear and insomnia. At the age of 32 years, she was institutionalized at a facility for the severely handicapped. On admission, she showed dwarfism (113 cm in height), emaciation (18 kg in weight) and pigmentation of the skin. Her head was small and her face showed a senile-like appearance with sunken eyes, cataract and malpositioned teeth. Neurological examination disclosed severe impairment of hearing and vision, dysarthria, muscle hypertonia, truncal and limb ataxia, spontaneous extension of the toes, and emotional instability. Her mental age was between 1 and 3 years. Laboratory examination showed hyperuricemia and slow conduction velocity of the peripheral nerves. Ultrasonography of the abdomen demonstrated thinning of the renal cortex. Computed tomography of her head showed diffuse cerebral atrophy, ventriculomegaly, and symmetrical calcification of the basal ganglia and cerebellar medulla (Fig. 1). On magnetic resonance imaging, the calcified lesions showed T1and T2-shortening. The cerebral white matter was atrophic and showed patchy T1and T2elongation (Fig. 1). At the age of 34 years, restlessness and anxiety worsened. She refused to eat, had epileptic attacks, and underwent hydration and medication with neuroleptic, hypnotic and antiepileptic drugs. Several months later, she became somnolent and developed fever, vomiting and hypertension, followed by coma, muscle rigidity and abnormal respiration. A high serum level of creatine kinase suggested a diagnosis of neuroleptic malignant syndrome. After approximately a week, she died at the age of 35 years.

Preventive Strategies for Aspiration Pneumonia in Elderly Disabled Persons

Pneumonia is the fourth leading cause of death despite the availability of potent new antimicrobials in Japan. Aspiration of oropharyngeal bacterial pathogens to the lower respiratory tract is one of the most important risk factors for pneumonia. Impairments in swallowing and cough reflexes among disabled older persons, e.g., related to cerebrovascular disease, increase the risk of pneumonia. Thus, strategies to reduce the volumes and pathogenicity of aspirated material should be pursued. Since both swallowing and cough reflexes are mediated by endogenous substance P contained in the vagal and glossopharyngeal nerves, pharmacologic therapy using angiotensin-converting enzyme inhibitors, which decrease substance P catabolism, can improve both reflexes and result in the lowering of the risk of pneumonia. Similarly, since the production of substance P is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment with dopamine analogs or potentiating drugs such as amantadine can reduce the incidence of pneumonia. Furthermore, since mortality from infections correlates with cutaneous anergy, interventions that reverse these age-associated changes in the immune system are also effective. The main theme of this review is to discuss how pneumonia develops in disabled older people and to suggest preventive strategies that may reduce the incidence of pneumonia among these subjects.

Interventions to prevent pneumonia in older adults

Aspiration of oropharyngeal bacterial pathogens to the lower respiratory tract is one of the most common risk factors for pneumonia. Impairments in swallowing and cough reflexes among older adults, for example related to cerebrovascular disease, increase the risk of pneumonia. Thus, strategies to reduce the volumes and pathogenicity of aspirated material should be pursued. Since both swallowing and cough reflexes are mediated by endogenous substance P, pharmacologic therapy using angiotensin‐converting enzyme inhibitors, which decrease substance P catabolism, may improve both reflexes and result in the lowering of the risk of pneumonia. Similarly, since the production of substance P is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment with dopamine analogs or potentiating drugs such as amantadine, may affect the incidence of pneumonia. Furthermore, since mortality from infections correlates with cutaneous anergy, interventions that reverse these age‐associated changes in the immune system are also effective.

6: Movement disorders II: the hyperkinetic disorders.

Involuntary movements or hyperkinesias are classified into syndromes of chorea, ballism, tremor, dystonia, myoclonus and tics. The hyperkinesias are caused by disturbances in the circuitry connecting the cerebral cortex, thalamus, basal ganglia and cerebellum. Drugs are a common cause of movement disorders. The aim of management is to characterise the movement disorder, identify and treat the cause or institute symptomatic treatment. The genetic basis of many movement disorders is increasingly recognised. Where there are potential implications for family members, accurate diagnosis and counselling are particularly important.

Interventions to prevent pneumonia among older adults.

Pneumonia is a common cause of death in older people. Antimicrobial drugs do not prevent pneumonia and, because of increasingly resistant organisms, their value in curing infection will become more limited. Establishing new strategies to prevent pneumonia through consideration of the mechanisms of this devastating illness is essential. The purpose of this review is to discuss how pneumonia develops in older people and to suggest preventive strategies that may reduce the incidence of pneumonia among older adults. Aspiration of oropharyngeal bacterial pathogens to the lower respiratory tract is one of the most important risk factors for pneumonia; impairments in swallowing and cough reflexes among older adults, e.g., related to cerebrovascular disease, increase the risk for the development of pneumonia. Thus, strategies to reduce the volumes and pathogenicity of aspirated material should be pursued. For example, since both swallowing and cough reflexes are mediated by endogenous substance P, pharmacologic therapy using angiotensin-converting enzyme inhibitors, which decrease substance P catabolism, may improve both reflexes and result in the lowering of the risk of pneumonia. Similarly, since the production of substance P is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment with dopamine analogs or potentiating drugs such as amantadine (and, of course, prevention of cerebral vascular disease, which can result in basal ganglia strokes) should affect the incidence of pneumonia. The purpose of this review is to consider promising pharmacologic treatments as methods of preventing pneumonia in older adults and to review other proven strategies, e.g., infection control and cerebrovascular disease prevention that will lessen the incidence of pneumonia.

Multifocal low-signal brain lesions on T2*-weighted gradient-echo imaging.

Multifocal small low-signal lesions on T2*-weighted gradient-echo (GE) MRI are reported to be common in the brain of hypertensive patients. We examined factors associated with these lesions. For one year, we routinely obtained T2*-weighted GE images (TR 1000 TE 30 ms, flip angle = 20 degrees) in all adult patients (314) who underwent brain MRI in our hospital, using a 1.5 T superconducting magnet. Patients with multifocal small low-signal lesions with a known or presumed pathogenesis or any condition which may cause intracerebral haemorrhage, such as brain tumours, were excluded from further analysis. Thus, 191 cases remained (104 men and 87 women; age, 62.8+/-11.0 years, range, 30-89 years). The overall prevalence of multifocal small low-signal lesions on the GE images was 15.2% (29/191); they were commonly in the cerebral white matter and basal ganglia. They were detected in 12 (52.2%) of the 23 patients with prior symptomatic brain hemorrhage, 12 (20.7%) of the 58 with prior symptomatic infarcts, and only five (4.5%) of 110 without a prior stroke. Logistic regression analysis indicated that multifocal small low-signal lesions were significantly correlated with a symptomatic acute brain haemorrhage (odds ratio, 13.17), chronic hypertension (4.00) and a symptomatic acute infarct (3.71). The association with symptomatic acute brain haemorrhage suggests that this finding may represent subclinical microhaemorrhage. The diagnostic potential of this finding to identify individuals at risk of symptomatic intracerebral haemorrhage may require further investigation.

SPINAL CORD DISEASES—DIAGNOSIS AND TREATMENT.

Knowledge about the clinical aspects, diagnosis and treatment of spinal cord diseases has lagged behind that of diseases involving other regions which concern clinical neurologists—namely the cerebral hemispheres, basal ganglia, cerebellum, brainstem, peripheral nerves and muscle. Reasons for this relative information gap abound: the spinal cord is a very long cylindrical structure with a very small diameter that is quite difficult to access because of its surrounding bony fortress and anatomical features; biopsy material is rarely available during life for fear of causing major paralytic deficits; diagnostic imaging technologies are imprecise in defining the spinal cord parenchyma; the spinal cord vasculature is difficult to visualize. Most neurology house officers have relatively little exposure to patients with spinal cord diseases in comparison with the frequency that they see brain and neuromuscular conditions. Spinal Cord Diseases—Diagnosis and Treatment is an attempt to bridge this information gap. This volume is part of the very successful Marcel Dekker series on Neurological Disease and Therapy. The editors of this volume have generated a 672 page hardback book that includes 29 chapters …

Contrast agent overdose causing brain retention of contrast, seizures, and parkinsonism

A patient received an overdose of intravascular contrast medium and experienced protracted seizures associated with radiographic evidence of prolonged retention of the contrast agent in the cerebral cortex, basal ganglia, and thalami. This is only the second report and the first survivor of a similar neurologic syndrome occurring in a patient after contrast agent overdose. After the seizures resolved, there was a transient period of parkinsonism probably due to the toxic effect of contrast on the basal ganglia.

1559 A network model of cerebral cortex and basal ganglia which generates voluntary movements

1559 A network model of cerebral cortex and basal ganglia which generates voluntary movements

Relationship between glial reaction to a stab wound and tumor development after receiving transplacental ethylnitrosourea in the rat

Fisher 344 rats born from mothers treated with ethylnitrosourea (ENU) 50 mg/kg intravenously were injured at the 1st and 2nd month of extrauterine life by a transcranial stab. The wound affected cerebral cortex, white matter and basal ganglia. The animals were killed 15 and 45 days and 5 months after injury and cell reaction was studied histologically and immunohistochemically. Bromodeoxyuridine (BrdUrd) was administered 1 h before sacrifice and the labeled cells were evaluated. In ENU-treated rats injured at 1 month of age only minor differences were found in comparison with injured controls. In ENU rats injured at 2 months of age and killed 15 days later, a higher number of BrdUrd-labeled cells was found in comparison with controls; 45 days after injury the cell reaction acquired the aspect of a microtumor, however, no microtumor unrelated with the needle track was present. In ENU rats killed 5 months after the injury, there was no difference between injured and not injured ENU-treated rats, as far as the aspect and the number of tumors were concerned. The tumor phenotype was, thus, anticipated by the cell response to trauma in ENU rats. The interpretation is that the additional cell division, in response to trauma, anticipate not only the phenotypic, but also the cell kinetics changes, as indicated by BrdUrd labeling.

Dixyrazine, a phenothiazine derivate, can prevent brain oedema induced by intracarotid injection of protamine sulphate

The present study was performed to determine whether an opening of the blood-brain barrier (BBB) induced by intracarotid infusion of protamine sulphate necessarily leads to brain oedema and, if so, whether dixyrazine, a phenothiazine, can prevent the oedema. Evans blue albumin was used to detect BBB opening. Endogenous serum albumin was determined in CSF sampled before and after protamine infusion. The brain specific gravity, a sensitive indicator of brain oedema, was determined one hour after intracarotid infusion of 5 or 10 mg protamine sulphate in 100 or 200 microliters solvent in rats. Both doses opened the BBB and the CSF albumin was significantly increased (p less than 0.05 for 5 mg and p less than 0.01 for 10 mg protamine sulphate). However, only 10 mg protamine significantly reduced the specific gravity in the cerebral cortex and basal ganglia in the right (injected) hemisphere. Pretreatment with dixyrazine 10 mg/kg completely prevented the brain oedema and significantly reduced the albumin increase in CSF. We conclude that a) a moderate opening of BBB induced by 5 mg protamine sulphate does not lead to brain oedema and b) dixyrazine can prevent the brain oedema induced by 10 mg protamine sulphate.

Effect of haloperidol on immunoreactive neuropeptide Y in rat cerebral cortex and basal ganglia

To clarify the dopaminergic regulation of neuropeptide Y (NPY) neurons, the effect of haloperidol on NPY in basal ganglia and the cerebral cortex of the rat brain was investigated by sensitive radioimmunoassay and immunocytochemistry using antiserum against rat NPY. After repeated intraperitoneal injections of haloperidol (5 mg/kg) for 6 days, the content of immunoreactive NPY was significantly decreased in the caudate-putamen, but significantly increased in the lateral prefrontal cortex. After treatment for 21 days, the content of immunoreactive NPY in the caudate-putamen remained significantly low, but the extent of change in the lateral prefrontal cortex diminished. In the medial prefrontal cortex, piriform cortex, parietal cortex and nucleus accumbens, no significant changes were found after treatment for either 6 or 21 days. These findings were compatible with those obtained by immunocytochemistry using the same antiserum: an increase of immunoreactive fibers and terminals in the lateral prefrontal cortex and their decrease in the caudate-putamen. However, in the nucleus accumbens the density of immunoreactive fibers and terminals was decreased in the rostral portion, but not in the caudal portion after haloperidol treatment for 6 and 21 days. These findings suggest that dopaminergic afferents region-specifically regulate dopamine-sensitive NPY neurons in the rat brain.

Cerebral diaschisis in patients with malignant glioma

A positron emission tomography study using [18F]-fluorodeoxyglucose was undertaken to identify and quantitate whether diaschisis occurred in cerebral cortex, basal ganglia, or thalamus, as well as in cerebellar cortex and dentate nuclei in patients with malignant glioma. The relationship between diaschisis in these cerebral structures and clinically significant hemiparesis in patients was analysed. A 30% decrease in the regional metabolic rate for glucose in the cerebellar hemisphere contralateral to the tumor, and ipsilateral to the motor deficit, was identified and was statistically significant (p greater than 0.001). Decreased metabolism in the cerebellar hemisphere contralateral to the tumor was not seen in patients without hemiparesis. Parietal lobes affected by tumor had a larger decrease in metabolism than did frontal lobes with tumor (p greater than 0.01). The overall metabolism of the unaffected cerebellar hemisphere, relative to the peak metabolic activity of the brain, was not depressed in patients with tumor. In addition, the activity of subcortical nuclei was relatively unaffected by adjacent tumor or motor deficit.

High affinity serotonin binding sites in human brain: a comparison of cerebral cortex and basal ganglia

The high-affinity binding of 3H-serotonin and 3H-DPAT was studied in membrane preparations and tissue sections of cerebral cortex and basal ganglia of human brain. In tissue sections, 3H-serotonin bound to sites present at high density in the cerebral cortex, hippocampus and basal ganglia. 3H-DPAT bound predominantly to the outer layers of the cerebral cortex and the hippocampus, no significant binding was observed in the basal ganglia. In cortical membranes 3H-serotonin bound to a heterogeneous population of sites, one of which was similar to a binding site labelled by 3H-DPAT (the putative 5HT-1A receptor). 3H-serotonin binding to membranes prepared from the putamen displayed low affinity for DPAT, mesulergine and spiperone, RU24969 was considerably less potent than serotonin itself. This 3H-serotonin binding site does not have the properties of those sites described in rodent brain (5HT-1A, 5HT-1B, and 5HT-1C), and may represent a novel serotoninergic binding site.