Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic degenerative diseases caused by genetic mutations and characterized by iron deposition in the central nervous system, especially in the basal ganglia, with an overall incidence rate of 2/1 000 000-3/1 000 000. Major clinical manifestations are extrapyramidal symptoms. This disease is presently classified into 14 different subtypes based on different pathogenic genes, and its pathogenesis and treatment remain unclear. This article summarizes the research advances in the pathogenesis and treatment of NBIA, so as to help pediatricians understand this disease and provide a reference for subsequent research on treatment.
Basal Ganglia ; Basal Ganglia Diseases ; Brain ; Humans ; Iron ; Iron Metabolism Disorders/therapy*

BACKGROUND: Normal pressure hydrocephalus (NPH) is a poorly understood condition, which typically presents with the triad of gait disturbance, urinary incontinence and cognitive decline. Diagnosis of NPH is often challenging due to its varied presentation and overlap with other neurodegenerative diseases including multiple system atrophy (MSA). CASE REPORT: A 68-year-old male developed rapidly progressive gait difficulty, urinary incontinence and memory impairment. Neurologic examination showed parkinsonism affecting the right side and impaired postural reflexes. Brain MRI showed enlargement of the ventricles and narrowing of the high convexity cerebrospinal fluid (CSF) spaces with relative dilated Sylvian fissure, the supporting features of NPH. 18F-fluorinated-N-3-fluoropropyl-2-b-carboxymethoxy-3-b-(4-iodophenyl) nortropane (¹⁸F-FP-CIT) PET showed decreased FP-CIT binding in the left posterior putamen and ¹⁸F-fluorodeoxyglucose PET showed decreased metabolism in the left basal ganglia, consistent with findings of MSA. CSF removal was performed and the symptoms were improved. The patient underwent ventriculo-peritoneal shunt and his gait and cognition improved. CONCLUSIONS: NPH is a potentially treatable neurological disorder. Therefore, it is necessary to consider the possibility of accompanying NPH when hydrocephalus is present in other neurodegenerative diseases.
Aged ; Basal Ganglia ; Brain ; Cerebrospinal Fluid ; Cognition ; Diagnosis ; Gait ; Humans ; Hydrocephalus* ; Hydrocephalus, Normal Pressure ; Magnetic Resonance Imaging ; Male ; Memory ; Metabolism ; Multiple System Atrophy* ; Nervous System Diseases ; Neurodegenerative Diseases ; Neurologic Examination ; Parkinsonian Disorders ; Putamen ; Reflex ; Urinary Incontinence ; Ventriculoperitoneal Shunt

OBJECTIVETo explore the role of HIV-1 tat gene variations in AIDS dementia complex (ADC) pathogenesis.

METHODSHIV-1 tat genes derived from peripheral spleen and central basal ganglia of an AIDS patient with ADC and an AIDS patient without ADC were cloned for sequence analysis. HIV-1 tat gene sequence alignment was performed by using CLUSTAL W and the phylogentic analysis was conducted by using Neighbor-joining with MEGA4 software. All tat genes were used to construct recombinant retroviral expressing vector MSCV-IRES-GFP/tat. The MSCV-IRES-GFP/tat was cotransfected into 293T cells with pCMV-VSV-G and pUMVC vectors to assemble the recombinant retrovirus. After infection of gliomas U87 cells with equal amount of the recombinant retrovirus, TNF-α, and IL-1β concentrations in the supernatant of U87 cells were determined with ELISA.

RESULTSHIV-1 tat genes derived from peripheral spleen and central basal ganglia of the AIDS patient with ADC and the other one without ADC exhibited genetic variations. Tat variations and amino acid mutation sites existed mainly at Tat protein core functional area (38-47aa). All Tat proteins could induce U87 cells to produce TNF-α and IL-1β, but the level of IL-1β production was different among Tat proteins derived from the ADC patient's spleen, basal ganglia, and the non-ADC patient's spleen. The level of Tat proteins derived from the ADC patient's spleen, basal ganglia, and the non-ADC patient's spleen were obviously higher than that from the non-ADC patient's basal ganglia.

CONCLUSIONTat protein core functional area (38-47aa) may serve as the key area of enhancing the secretion of IL-1β. This may be related with the neurotoxicity of HIV-1 Tat.

AIDS Dementia Complex ; metabolism ; pathology ; virology ; Adult ; Amino Acid Sequence ; Basal Ganglia ; virology ; Cell Line, Tumor ; Gene Expression Regulation, Viral ; Genes, tat ; HIV-1 ; genetics ; pathogenicity ; Humans ; Interleukin-1beta ; biosynthesis ; genetics ; secretion ; Middle Aged ; Molecular Sequence Data ; Neuroglia ; pathology ; secretion ; Spleen ; virology ; Tumor Necrosis Factor-alpha ; biosynthesis ; genetics ; secretion ; tat Gene Products, Human Immunodeficiency Virus ; genetics ; physiology

BACKGROUND: Cognitive intervention (CI) is a nonpharmacological approach used to compensate for cognitive impairment. It is categorized into cognitive training, cognitive stimulation and cognitive rehabilitation. Several studies showed that CI could induce cognitive enhancement and reduction of risk for future cognitive decline in patients with brain injury. We investigated effects of CI on cognitive functions and brain glucose metabolism based on serial cognitive assessments and [18F]-Fluorodexoxyglucose positron emission tomography (FDG-PET) in a patient with carbon monoxide (CO) intoxication. METHODS: A 40-year-old man presented with memory impairment and abnormal behaviors such as apathy, indifference, and perseveration 2-month after CO intoxication. Brain magnetic resonance image (MRI) demonstrated high signal changes in the bilateral basal ganglia, hippocampus and the subcortical white matter on T2 weighted images. FDG-PET also showed glucose hypometabolism in the bilateral hippocampus, basal ganglia, and the subcortical white matter. A detailed neuropsychological evaluation revealed multiple cognitive impairments in memory, language and frontal functions. He received twice a week sessions of 60-minute group-based cognitive intervention for 12 weeks. Several neuropsychological examinations and FDG-PETs were conducted at baseline and after CI. RESULTS: After CI, he showed improvements in memory and frontal functions compared with baseline performances. These cognitive improvements persisted by the 7-month follow-up. The extent of glucose hypometabolism was decreased 1-month after CI, however increased 8-month after CI. CONCLUSIONS: This case study suggested that CI could enhance cognitive functions and improve glucose metabolism in a patient with CO intoxication. Also, the effects of CI on cognitive functions seem to be last at least 7-month after training.
Adult ; Apathy ; Basal Ganglia ; Brain ; Brain Injuries ; Carbon Monoxide* ; Follow-Up Studies ; Glucose ; Hippocampus ; Humans ; Memory ; Metabolism ; Neuronal Plasticity ; Neuropsychology ; Positron-Emission Tomography ; Rehabilitation

OBJECTIVETo investigate the metabolic changes on proton magnetic resonance spectroscopy (¹H-MRS) in patients with first left basal ganglia infarction and their relationship with depression.

METHODSTwenty-two patients with first left basal ganglia infarction and 10 matched healthy controls were recruited in the study. Patients and controls underwent (1)H MRS scan and the spectrum of N-acetyl aspartic acid (NAA), choline (Cho) and creatinine (Cr) was recorded at the first week (D7) and 1 month after onset (M1), respectively. National Institutes of Health Stroke Scale (NIHSS), Ability of daily life (ADL), Hamilton Depression Scale (HAMD) were evaluated at D7, M1 and M6 after onset. The patients were classified into two groups: post-stroke depression (PSD) and non-post-stroke depression (NPSD) according to the result of HAMD.The differences of (1)H-MRS between these two groups were compared and their relationship with NIHSS and ADL was analyzed.

RESULTSAmong 22 patients 10 were diagnosed as PSD and 12 were NPSD. Compared to controls, NAA/Cr was significantly lower and Cho/Cr was significantly higher (P <0.05)in left prefrontal white matter and left basal ganglia in patients with infarct. Patients with PSD showed a lower NAA/Cr and higher Cho/Cr than NPSD patients (P <0.05). At M1 after onset, NAA/Cr in the left prefrontal white matter was significantly correlated with NIHSS (r=-0.551, P =0.032), while Cho/Cr was correlated with ADL (r=0.682, P=0.005)in PSD patients.

CONCLUSIONMetabolic changes shown on (1)H-MRS in patients with basal ganglia infarction may predict the occurrence of PSD.

Adult ; Basal Ganglia ; pathology ; Case-Control Studies ; Cerebral Infarction ; complications ; Depression ; diagnosis ; etiology ; metabolism ; Female ; Humans ; Magnetic Resonance Spectroscopy ; methods ; Male ; Middle Aged ; Protons

Recent studies have reported that cognitive inflexibility associated with impairments in a frontal-striatal circuit and parietal region is a core cognitive deficit of obsessive-compulsive disorder (OCD). However, few studies have examined progressive changes in these regions following clinical improvement in obsessive-compulsive symptoms. To determine if treatment changes the aberrant activation pattern associated with task switching in OCD, we examined the activation patterns in brain areas after treatment. The study was conducted on 10 unmedicated OCD patients and 20 matched controls using event-related functional magnetic resonance imaging. Treatment improved the clinical symptoms measured by the Yale-Brown Obsessive Compulsive Scale and behavioral flexibility indicated by the switching cost. At baseline, OCD showed significantly less activation in the dorsal and ventral frontal-striatal circuit and parietal regions under the task-switch minus task-repeat condition compared with controls. After treatment, the neural responses in the ventral frontal-striatal circuit in OCD were partially normalized, whereas the activation deficit in dorsal frontoparietal regions that mediate shifting attention or behavioral flexibility persisted. It is suggested that altered brain activation in ventral frontal-striatal regions in OCD patients is associated with their cognitive flexibility and changes in these regions may underlie the pathophysiology of OCD.
Adult ; Basal Ganglia/*metabolism ; Behavioral Symptoms/drug therapy ; Female ; Frontal Lobe/*drug effects/physiopathology ; Humans ; Magnetic Resonance Imaging ; Male ; Obsessive-Compulsive Disorder/*drug therapy/physiopathology ; Parietal Lobe/*drug effects/physiopathology

OBJECTIVETo probe the effect of sodium para-aminosalicylate (PAS-Na) on concentration of amino acid neurotransmitters including glutamate (Glu), glutamine (Gln), glycine (Gly) and gamma-aminobutyric acid (GABA) in basal ganglia of subacute manganese (Mn)-exposed rats.

METHODSForty Sprague-Dawley male rats were randomly divided into the control, Mn-exposed, low dose PAS-Na (L-PAS) and high dose PAS-Na (H-PAS) groups. Rats in experiment groups received daily intraperitoneally injections of manganese chloride (MnCl₂ · 4H₂O, 15 mg/kg), while rats in control group received daily intraperitoneally injections of normal saline (NS), all at 5 days/week for 4 weeks. Then the rats in PAS groups followed by a daily subcutaneously dose of PAS-Na (100 and 200 mg/kg as the L-PAS and H-PAS groups, respectively) for another 3 and 6 weeks; while the rats in Mn-exposed and control group received NS. The concentrations of Glu, Gln, Gly and GABA in basal ganglia of rat was detected by the high performance liquid chromatography fluorescence detection technique.

RESULTSAfter treating with PAS-Na for 3 weeks, the concentration of Gly in the Mn-exposed rats decreased to (0.165 ± 0.022) µmol/L (control = (0.271 ± 0.074) µmol/L, Mn vs control, t = 4.65, P < 0.05). After the further 6-week therapy with PAS-Na, the concentrations of Glu, Gln, Gly in the Mn-exposed rats were lower than those of the control rats ((0.942 ± 0.121), (0.377 ± 0.070), (0.142 ± 0.048), (1.590 ± 0.302), (0.563 ± 0.040), (0.247 ± 0.084) µmol/L; t = 7.72, 5.85, 4.30, P < 0.05); and also lower than in L-PAS and H-PAS groups, whose concentrations were separately (1.268 ± 0.124), (1.465 ± 0.196), (0.497 ± 0.050), (0.514 ± 0.103), (0.219 ± 0.034) µmol/L (L-PAS Glu and Gln vs Mn, t = 3.87, 3.77, P < 0.05; H-PAS Glu, Gln and Gly vs Mn, t = 6.78, 4.70, 3.42, P < 0.05).

CONCLUSIONThe toxic effect of manganese on Glu, Gln and Gly in basal ganglia of Mn-exposed rats is obvious, especially appears earlier on Gly. The toxic effect still continues to develop when relieved from the exposure. PAS-Na may play an antagonism role in toxic effect of manganese on concentration of Glu, Gln and Gly in basal ganglia of Mn-exposed rats.

Amino Acids ; metabolism ; Animals ; Basal Ganglia ; drug effects ; metabolism ; Glutamic Acid ; metabolism ; Male ; Manganese ; toxicity ; Neurotransmitter Agents ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sodium Salicylate ; pharmacology ; gamma-Aminobutyric Acid ; metabolism

Neurodegeneration with brain iron accumulation (NBIA) is a disorder characterized by various mixtures of extrapyramidal, pyramidal or psychiatric abnormalities associated with iron accumulation in the basal ganglia. The mutations in the pantothenate kinase gene (PANK2) were found in approximately two thirds of the patients with NBIA. We report three patients wtih NBIA, and two of them showed mutations in the PANK2 gene.
Basal Ganglia ; Brain ; Humans ; Iron ; Iron Metabolism Disorders ; Neuroaxonal Dystrophies ; Phosphotransferases ; Phosphotransferases (Alcohol Group Acceptor)

PURPOSE: To investigate the general characteristics of glucose metabolism distribution and the functional deficit in the brain of children with developmental language delay (DLD), we compared functional neuroradiological studies such as positron emission tomography (PET) of a patient group of DLD children and a control group of attention- deficit hyperactivity disorder (ADHD) children. PATIENTS AND METHODS: Seventeen DLD children and 10 ADHD children under 10 years of age were recruited and divided into separate groups consisting of children less than 5 years of age or between 5 and 10 years of age. The PET findings of 4 DLD children and 6 control children whose ages ranged from 5 to 10 years were compared by Statistical Parametric Mapping (SPM) analysis. RESULTS: All of the DLD children revealed grossly normal findings in brain MRIs, however, 87.5% of them showed grossly abnormal findings in their PET studies. Abnormal findings were most frequent in the thalamus. The patient group showed significantly decreased glucose metabolism in both frontal, temporal and right parietal areas (p < 0.005) and significantly increased metabolism in both occipital areas (p < 0.05) as compared to the control group. CONCLUSION: This study reveals that DLD children may show abnormal findings on functional neuroradiological studies, even though structural neuroradiological studies such as a brain MRI do not show any abnormal findings. Frequent abnormal findings on functional neuroradiological studies of DLD children, especially in the subcortical area, suggests that further research with quantitative assessments of functional neuroradiological studies recruiting more DLD children and age-matched normal controls could be helpful for understanding the pathophysiology of DLD and other disorders confined to the developmental disorder spectrum.
Attention Deficit Disorder with Hyperactivity/metabolism/*pathology ; Basal Ganglia/abnormalities/metabolism/radionuclide imaging ; Brain/*abnormalities/metabolism/radionuclide imaging ; Caudate Nucleus/abnormalities/metabolism/radionuclide imaging ; Cerebellum/abnormalities/metabolism/radionuclide imaging ; Child ; Child, Preschool ; Glucose/metabolism ; Humans ; Language Development Disorders/metabolism/*pathology ; Magnetic Resonance Imaging ; Positron-Emission Tomography ; Thalamus/abnormalities/metabolism/radionuclide imaging

PURPOSE: Gender differences in personality are considered to have biological bases. In an attempt to understand the gender differences of personality on neurobiological bases, we conducted correlation analyses between regional brain glucose metabolism and temperament factors of personality in males and females. MATERIALS AND METHODS: Thirty-six healthy right-handed volunteers (18 males, 33.8+/-17.6 y; 18 females, 36.2+/-20.4 y) underwent FDG PET at resting state. Three temperament factors of personality (novelty seeking (NS), harm avoidance (HA), reward dependence (RD)) were assessed using Cloninger's 240-item Temperament and Character Inventory (TCI) within 10 days of FDG PET scan. Correlation between regional glucose metabolism and each temperament factor was tested using SPM2. RESULTS: In males, a significant negative correlation between NS score and glucose metabolism was observed in the bilateral superior temporal gyri, the hippocampus and the insula, while it was found in the bilateral middle frontal gyri, the right superior temporal gyrus and the left cingulate cortex and the putamen in females. A positive HA correlation was found in the right midbrain and the left cingulate gyrus in males, but in the bilateral basal ganglia in females. A negative RD correlation was observed in the right middle frontal and the left middle temporal gyri in males, while the correlation was found in the bilateral middle frontal gyri and the right basal ganglia and the superior temporal gyrus in females. CONCLUSION: These data demonstrate different cortical and subcortical metabolic correlates of temperament factors of personality between males and females. These results may help understand biological substrate of gender differences in personality and susceptibility to neuropsychiatric illnesses.
Basal Ganglia ; Brain ; Female ; Glucose ; Gyrus Cinguli ; Hippocampus ; Humans ; Male ; Mesencephalon ; Metabolism ; Positron-Emission Tomography ; Putamen ; Reward ; Temperament* ; Volunteers