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Background The clinical diagnosis of multiple system atrophy (MSA) is challenged by overlapping features with Parkinson's disease (PD) and late-onset ataxias. Additional biomarkers are needed to confirm MSA and to advance the understanding of pathophysiology. Positron emission tomography (PET) imaging of the translocator protein (TSPO), expressed by glia cells, has shown elevations in MSA. Objective In this multicenter PET study, we assess the performance of TSPO imaging as a diagnostic marker for MSA. Methods We analyzed [11 C]PBR28 binding to TSPO using imaging data of 66 patients with MSA and 24 patients with PD. Group comparisons were based on regional analysis of parametric images. The diagnostic readout included visual reading of PET images against clinical diagnosis and machine learning analyses. Sensitivity, specificity, and receiver operating curves were used to discriminate MSA from PD and cerebellar from parkinsonian variant MSA. Results We observed a conspicuous pattern of elevated regional [11 C]PBR28 binding to TSPO in MSA as compared with PD, with "hotspots" in the lentiform nucleus and cerebellar white matter. Visual reading discriminated MSA from PD with 100% specificity and 83% sensitivity. The machine learning approach improved sensitivity to 96%. We identified MSA subtype-specific TSPO binding patterns. Conclusions We found a pattern of significantly increased regional glial TSPO binding in patients with MSA. Intriguingly, our data are in line with severe neuroinflammation in MSA. Glia imaging may have potential to support clinical MSA diagnosis and patient stratification in clinical trials on novel drug therapies for an α-synucleinopathy that remains strikingly incurable. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Aims: In Wilson disease (WD), T2/T2*-weighted (T2*w) MRI frequently shows hypointensity in the basal ganglia that is suggestive of paramagnetic deposits. It is currently unknown whether this hypointensity is related to copper or iron deposition. We examined the neuropathological correlate of this MRI pattern, particularly in relation to iron and copper concentrations. Methods: Brain slices from nine WD and six control cases were investigated using a 7T-MRI system. High resolution T2*w images were acquired and R2* parametric maps were reconstructed using a multi-gradient recalled echo sequence. R2* was measured in the globus pallidus (GP) and the putamen. Corresponding histopathological sections containing the lentiform nucleus were examined using Turnbull iron staining, and double staining combining Turnbull with immunohistochemistry for macrophages or astrocytes. Quantitative densitometry of the iron staining as well as copper and iron concentrations were measured in the GP and putamen and correlated to R2* values. Results: T2*w hypointensity in the GP and/or putamen was apparent in WD cases and R2* values correlated with quantitative densitometry of iron staining. In WD, iron and copper concentrations were increased in the putamen compared to controls. R2* was correlated with the iron concentration in the GP and putamen whereas no correlation was observed for the copper concentration. Patients with more pronounced pathological severity in the putamen displayed increased iron concentration, which correlated with an elevated number of iron-containing macrophages. Conclusions: T2/T2*w hypointensity observed in vivo in the basal ganglia of WD patients is related to iron rather than copper deposits.

BACKGROUND The location of acute ischemic infarct can affect the clinical outcome of stroke patients. We aimed to develop a prognostic tool based on the topographic distribution of early ischemic changes on admission computed tomography (CT) scans. METHODS Using the albumin in acute stroke (ALIAS) trials dataset, patients with anterior circulation stroke were included for analysis. A 3-month modified Rankin scale (mRs) score > 2 defined disability/death; and ≤2 defined favorable outcome. A penalized logistic regression determined independent predictors of disability/death among components of admission CT scan Alberta Stroke Program Early CT score (ASPECTS). Follow-up 24-hour CT/MRI scans were reviewed for intracranial hemorrhage (ICH). RESULTS A simplified ASPECTS (sASPECTS) was developed including the caudate, lentiform nucleus, insula, and M5 components of ASPECTS—which were independent predictors of disability/death on multivariate analysis. There was no significant difference between ASPECTS and sASPECTS in prediction of disability/death (P = .738). Among patients with sASPECTS ≥ 1, the rate of favorable outcome was higher in those with intravenous (IV) thrombolytic therapy (501/837, 59.9%) versus those without treatment (91/183, 49.7%, P = .013); whereas among patients with sASPECTS of 0, IV thrombolysis was not associated with improved outcome. Also, patients with sASPECTS of 0 were more likely to develop symptomatic ICH (odds ratio = 2.62, 95% confidence interval: 1.49-4.62), compared to those with sASPECTS ≥ 1 (P = .004). CONCLUSIONS Topographic assessment of acute ischemic changes using the sASPECTS (including caudate, lentiform nucleus, insula, and M5) can predict disability/death in anterior circulation stroke as accurately as the ASPECTS; and may help predict response to treatment and risk of developing symptomatic ICH.

Background Subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) has been associated with the development of postoperative apathy. Debate on the causes of postoperative apathy continues, and the dominant hypothesis is that stimulation or dopaminergic drug reductions are causal in its development. We hypothesized that a preoperative predisposition to apathy also could exist. To this end, we sought to identify a preoperative metabolic pattern using [18]Fluorodeoxyglucose Positron Emission Tomography (PET), which could be associated with the occurrence of postoperative apathy after STN-DBS for PD. Methods Thirty-four patients with PD, not clinically apathetic, underwent an [18]Fluorodeoxyglucose-PET scan before surgery of STN-DBS, and were tested for the occurrence of apathy 1 y after surgery. Whole-brain voxel-based PET intergroup comparison (P < 0.005; corrected for the cluster) was evaluated between patients who developed apathy at 1 y and those who did not. Results Eight patients (23.5%) became apathetic after surgery. Motor improvement and decrease in dopaminergic treatment were similar in both postoperative apathy and non-apathy groups. We found a cluster of significantly greater metabolism in the postoperative apathy group within the cerebellum, brainstem (in particular ventral tegmental area), temporal lobe, insula, amygdala, lentiform nucleus, subgenual anterior cingulate, and inferior frontal gyrus. A metabolic value above 68 could discriminate patients who would develop postoperative apathy with 100% sensitivity and 88.5% specificity. Conclusions We describe a preoperative metabolic pattern associated with the development of apathy after STN-DBS in PD. This suggests the existence of a predisposition to apathy, which may further be triggered by perioperative drug modifications. © 2015 International Parkinson and Movement Disorder Society

BACKGROUND AND PURPOSE The “venous hypothesis” of multiple sclerosis (MS) postulates that intracranial venous congestion disintegrates the blood-brain barrier, resulting in iron accumulation in brain parenchyma triggering the inflammatory process of MS. Transcranial sonography (TCS) reveals brain parenchyma hyperechogenic alterations (BPHA) that are thought to reflect iron accumulation. We sought to investigate potential association of BPHA with chronic cerebrospinal venous insufficiency (CCSVI) in MS. METHODS MS patients were evaluated according to established TCS protocol for extrapyramidal disorders examining the presence of hyperechogenicities in different basal ganglia regions. Cerebral and cervical venous system was assessed according to proposed ultrasound protocol for CCSVI detection. RESULTS In a total of 32 MS patients (age = 40 ± 14 years; male = 41%; EDSS-score = 3.1 ± 2.2) brain parenchyma hyperechogenic alterations were detected in twelve (38%) patients. The two sonographers agreed independently in 28 (87.5%) of the 32 examinations, resulting in a substantial to almost perfect agreement (Cohen's weighted kappa: substantia nigra = 0.904, Lentiform nucleus = 0.871, Thalamus = 0.784, caudate nucleus = 0.651). Two (6%) patients fulfilled the neurosonology criteria of CCSVI, while in 7 patients (22%) one positive criterion was detected. No BPHA were observed in any MS patient fulfilling CCSVI criteria. The prevalence of one positive CCSVI feature did not differ (P = .999) among patients with present (25%) or absent (20%) BPHA. CONCLUSION There was no association of BPHA with CCSVI findings. Our findings do not support the “venous hypothesis” resulting in iron accumulation even in the few MS patients fulfilling CCSVI-criteria.

OBJECTIVES To develop and evaluate a method to quantify the T1-weighted magnetic resonance imaging signal intensity of the lentiform nuclei in dogs, and to determine if there is any significant difference in this signal intensity between dogs with portosystemic shunts and a control group. MATERIALS AND METHODS A retrospective blinded study was performed to investigate the reliability and use of a quantitative method for assessing the T1-weighted magnetic resonance imaging signal intensity of the lentiform nuclei in dogs with and without portosystemic shunts. The lentiform nuclei index (mean lentiform nucleus signal intensity/mean white matter signal intensity) was calculated for nine dogs with portosystemic shunts and a control group of 14 dogs. RESULTS The intra- and inter-observer intraclass correlation coefficients were considered excellent (>0 · 75), suggesting that the lentiform nuclei index is a reliable method. The dogs with portosystemic shunts had a higher lentiform nuclei index than the control group (P = 0 · 0127). CLINICAL SIGNIFICANCE This method of quantifying the T1-weighted magnetic resonance imaging signal intensity of the lentiform nuclei was reliable and showed that dogs with portosystemic shunts tend to have increased signal intensity. Further prospective studies are necessary to investigate the clinical significance and applications of these findings.

Neosporosis is a polysystemic disease that can affect dogs of any age and can cause inflammation of the central nervous system. Antemortem diagnosis can be challenging, as clinical and conventional laboratory test findings are often nonspecific. A previous report described cerebellar lesions in brain MRI studies of seven dogs and proposed that these may be characteristic for central nervous system Neosporosis. The purpose of this retrospective study was to describe MRI characteristics in another group of dogs with confirmed central nervous system neosporosis and compare them with the previous report. The hospital's database was searched for dogs with confirmed central nervous system neosporosis and four observers recorded findings from each dog's MRI studies. A total of four dogs met inclusion criteria. Neurologic examination was indicative of a forebrain and cerebellar lesion in dog 2 and multifocal central nervous system disease in dogs 1, 3, and 4. Magnetic resonance imaging showed mild bilateral and symmetrical cerebellar atrophy in three of four dogs (dogs 2, 3, 4), intramedullary spinal cord changes in two dogs (dogs 3, 4) and a mesencephalic and metencephalic lesion in one dog (dog 2). Multifocal brain lesions were recognized in two dogs (dogs 1, 4) and were present in the thalamus, lentiform nucleus, centrum semiovale, internal capsule, brainstem and cortical gray matter of the frontal, parietal or temporal lobe. Findings indicated that central nervous system neosporosis may be characterized by multifocal MRI lesions as well as cerebellar involvement in dogs.

Purpose To demonstrate in idiopathic normal pressure hydrocephalus (iNPH) patients by dynamic susceptibility contrast MRI a reduced preoperative cerebral blood flow (CBF) which correlates with the severity of clinical symptoms and predicts shunt outcome. Materials and Methods In cortical, subcortical, periventricular regions and along peri-and paraventricular profiles absolute perfusion values were estimated by multi-slice DSC MRI in 21 iNPH patients and 16 age-matched healthy individuals (HI). Relative CBF (rCBF), calculated with the occipital cortex as internal reference, was used for comparison between groups and for correlation analysis between regional rCBF and symptoms or outcome. Results iNPH patients showed significantly decreased rCBF in the basal medial frontal cortex, hippocampus, lentiform nucleus, periventricular white matter (PVWM), central grey matter and the global parenchyma as compared to HI. iNPH patients with higher preoperative rCBF in the PVWM performed better in clinical tests. A lower overall preoperative function resulted in a more obvious recovery after shunt insertion. Shunt-responders had higher rCBF values in the basal medial frontal cortex than non-responders. Conclusion DSC MRI perfusion is a potentially useful diagnostic tool in iNPH and perfusion based criteria might be possible predictors of shunt response. J. Magn. Reson. Imaging 2014;39:1533–1542. © 2013 Wiley Periodicals, Inc.

Measurements of the concentrations of γ-aminobutyric acid (GABA) and glutamate in the motor cortices and lentiform nuclei of dystonic patients using single-voxel (1)H magnetic resonance spectroscopy (MRS) have yielded conflicting results so far. This study aimed to investigate dynamic changes in metabolite concentrations after stimulation of the motor cortices in patients with upper limb dystonia. Using single-voxel MRS at 3 T, the concentrations of GABA, glutamate plus glutamine, and N-acetylaspartate were measured bilaterally in the primary sensorimotor cortex, lentiform nucleus, and occipital region before and after 5-Hz transcranial magnetic stimulation (TMS) over the dominant motor cortex. Data obtained from 15 patients with upper limb primary dystonia were compared with data obtained from 14 healthy volunteers. At baseline, there was no group difference in concentration of metabolites in any region. rTMS induced a local (in the stimulated motor cortex) decrease of N-acetylaspartate (P < .006) to the same extent in healthy volunteers and patients. GABA concentrations were modulated differently, however, decreasing mildly in patients and increasing mildly in healthy volunteers (P = .05). There were no remote effects in the lentiform nucleus in either group. The stimulation-induced changes in metabolite concentrations have been interpreted in view of the increased energy demand induced by rTMS. The dynamics of the GABA concentration were specifically impaired in dystonic patients. Whether these changes reflect changes in the extrasynaptic or synaptic GABA component is discussed.

Persistent neuropathic pain due to peripheral nerve degeneration in diabetes is a stressful symptom; however, the underlying neural substrates remain elusive. This study attempted to explore neuroanatomical substrates of thermal hyperalgesia and burning pain in a diabetic cohort due to pathologically proven cutaneous nerve degeneration (the painful group). By applying noxious 44°C heat stimuli to the right foot to provoke neuropathic pain symptoms, brain activation patterns were compared with those of healthy control subjects and patients with a similar degree of cutaneous nerve degeneration but without pain (the painless group). Psychophysical results showed enhanced affective pain ratings in the painful group. After eliminating the influence of different pain intensity ratings on cerebral responses, the painful group displayed augmented responses in the limbic and striatal structures, including the perigenual anterior cingulate cortex (ACC), superior frontal gyrus, medial thalamus, anterior insular cortex, lentiform nucleus (LN), and premotor area. Among these regions, blood oxygen level-dependent (BOLD) signals in the ACC and LN were correlated with pain ratings to thermal stimulations in the painful group. Furthermore, activation maps of a simple regression analysis as well as a region of interest analysis revealed that responses in these limbic and striatal circuits paralleled the duration of neuropathic pain. However, in the painless group, BOLD signals in the primary somatosensory cortex and ACC were reduced. These results suggest that enhanced limbic and striatal activations underlie maladaptive responses after cutaneous nerve degeneration, which contributed to the development and maintenance of burning pain and thermal hyperalgesia in diabetes. Hum Brain Mapp 34:2733–2746, 2013. © 2012 Wiley Periodicals, Inc.

Previous studies have evaluated motor and extramotor cerebral cortical regions in patients with amyotrophic lateral sclerosis (ALS) using 1H MRS, but none have evaluated the thalamus or basal ganglia. The objective of this exploratory study was to evaluate the subclinical involvement of the basal ganglia and thalamus in patients with ALS using 1H MRS. Fourteen patients (52 ± 7 years) with sporadic definite ALS and 17 age-matched controls were studied using volumetric MRSI on a 3-T scanner. The concentration of the metabolites N-acetylaspartate (NAA), choline (Cho) and their ratio (NAA/Cho) were obtained bilaterally from the basal ganglia (lentiform nucleus, caudate) and thalamus. The maximum rates of finger and foot tap and lip and tongue movements were obtained to assess extrapyramidal and pyramidal tract function. In patients with ALS, relative to controls, the NAA concentration was significantly lower (p

Introduction Although performance deficits in place learning have been reported in fetal alcohol spectrum disorders (FASD), neural correlates of these deficits have not been investigated. This functional magnetic resonance imaging (fMRI) study of 57 children (41 alcohol‐exposed; 16 controls; mean age = 9.4 years; 29 boys) examined effects of prenatal alcohol exposure (PAE) on place learning in a virtual environment, the computer‐generated (CG) arena. Methods Functional magnetic resonance imaging data were acquired while children passively viewed a recording of an experimenter completing the task. Visible‐target blocks involved navigation to a visible platform. During invisible‐target blocks, the platform appeared only when the experimenter moved over it. After the scan, all children performed a post‐test during which they had to navigate to the location of the invisible platform. Results Although there were no group differences in post‐test performance for sex or FASD diagnosis, PAE in boys was associated with poorer performance and reduced activation in the parahippocampal gyrus (PHG), precuneus, posterior cingulate, frontal and temporal lobes, caudate, insula, claustrum, lentiform nucleus, and thalamus. By contrast, PAE was not associated with performance or activation in any regions in girls. Discussion and conclusion Girls and boys are known to use different navigation strategies. Boys rely more on an allocentric navigational strategy and girls more on landmarks. Poorer recruitment of the PHG, a region known to mediate allocentric navigation, in more heavily exposed boys may explain the observed dose‐dependent place learning deficit. The absence of PAE effects in girls suggests that landmark‐based navigational strategies may be less affected by alcohol exposure.

BACKGROUND AND PURPOSE Magnetic resonance spectroscopy (MRS) allows the measurement of a number of brain tissue metabolites in vivo, including N-acetylaspartate (NAA), a putative marker of neuronal integrity. Unlike single voxel MRS, magnetic resonance spectroscopic imaging (MRSI) enables quantification of these metabolites simultaneously from multiple anatomically localized voxels. Both single voxel MRS and MRSI allow the absolute quantification of these metabolites and, when combined with tissue segmentation, can give accurate metabolite concentrations even in the presence of partial volume effects from nearby cerebrospinal fluid. METHODS Using MRSI with cubic voxels with a nominal volume of 1.0 cm(3), we tested the hypothesis that concentrations of NAA in the basal ganglia in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) would show differences compared to Parkinson's disease (IPD). NAA values (in mM) from MRSI voxels centred to the putamen, pallidum and thalamus were obtained from 11 patients with IPD, 11 with MSA-P, six with MSA-C, 13 with PSP and 18 controls. The mean concentrations of NAA and its bulk grey and white matter values were also estimated over the whole brain slab. RESULTS N-acetylaspartate concentrations in the pallidum, putamen and lentiform nucleus were significantly lower in patients with MSA-P and PSP compared to IPD and controls. The putaminal values were also significantly reduced in PSP compared to MSA-P. There were no significant differences between groups in the thalamus and over the whole brain slab. CONCLUSION Our findings support the notion that MRSI can potentially quantify basal ganglia cellular pathology in MSA and PSP.

WOS: 000243637000014, PubMed ID: 17250509, Background: The purpose of this study was to emphasize the clinical and imaging findings of 19 child cases of cerebral hemiatrophy. Methods:A total of 11 male and eight female patients underwent assessment with computed tomography and magnetic resonance imaging. The patients ranged from 1 to 17 years in age. The evaluated parameters were: location of the lesions, midline structural shift effect, ipsilateral calvarial and parenchymal changes. Results:Left cerebral hemiatrophy was seen in 14 of the cases while right cerebral hemiatrophy was observed in five cases. Unilateral calvarial thickening was seen in 11 cases, hyperpneumatization of paranasal sinuses in five, and hypoplasia of the middle frontal cranial fossa in three patients. Cerebral peduncle atrophy was noted in seven cases. In total, 11 patients had thalamic atrophy and lentiform nucleus hypoplasia. In one case, cerebral hemiatrophy was associated with ipsilateral large schizencephalic cleft and absence of the septum pellucidum, whereas in another case, there was diffuse cerebellar atrophy associated with cerebral hemiatrophy. Conclusions: Computed tomography and, in particular, magnetic resonance imaging are the procedures of choice with respect to assessment of the etiology and extent of cerebral parenchymal involvement in cerebral hemiatrophy.

Summary: Purpose: Previous studies using diffusion MRI in patients with temporal lobe epilepsy have shown abnormal water diffusion in the hippocampus. Because thalamus and lentiform nuclei are considered important for the regulation of cortical excitability and seizure propagation, we analyzed diffusion tensor imaging (DTI) abnormalities in these subcortical structures and in hippocampus of children with partial epilepsy with and without secondary generalization. Methods: Fourteen children with partial epilepsy involving the temporal lobe underwent MRI including a DTI sequence. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained in the hippocampus, thalamus, and lentiform nucleus, and compared with DTI data of 14 control children with no epilepsy, as well as glucose positron emission tomography (PET) findings. Results: Decreased FA (p < 0.001) and increased ADC (p = 0.003) values were found in the hippocampi ipsilateral to the seizure focus. Significant FA decreases (p = 0.002) also were seen in the contralateral hippocampi, despite unilateral seizure onset and excellent surgical outcome in patients who underwent surgery. ADC values showed a trend for increase in the thalami ipsilateral to the epileptic focus in the seven children with secondarily generalized seizures (p = 0.09). No group differences of ADC or FA were found in the lentiform nuclei. The DTI variables did not correlate with regional glucose metabolism in any of the structures analyzed. Conclusions: Increased ADC values in hippocampus can assist in lateralizing the seizure focus, but decreased FA in the contralateral hippocampus suggests that it too may be dysfunctional despite unilateral seizure onset. Less-robust thalamic abnormalities of water diffusion in patients with secondarily generalized seizures suggest secondary involvement of the thalamus, perhaps due to recruitment of this structure into the epileptic network; however, this must be confirmed in a larger population. DTI appears to be a sensitive method for detection abnormalities in children with partial epilepsy, even in structures without apparent changes on conventional MRI.

Background: Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) each have distinctive clinical features, but diagnosis is often uncertain. Our purpose was to evaluate whether localized, single-voxel proton magnetic resonance spectroscopy (1H-MRS) could distinguish between typical CBD and PSP patients. Methods: The study included 10 patients with CBD, nine with PSP and eight age-matched normal healthy subjects. A single-voxel method of 8 cm3 (2 × 2 × 2 cm) was used for 1H-MRS. The volume of interest was selected at the frontoparietal cortex and the lentiform nucleus. Results: Patients with CBD had significantly reduced ratios of N-acetylaspartate to choline-containing compounds (NAA/Cho), N-acetylaspartate to creatine and phosphocreatine (NAA/Cr) in the frontoparietal cortex and lentiform nucleus compared with the normal subjects. Patients with PSP had significantly reduced NAA/Cho and NAA/Cr ratios in the lentiform nucleus, but not in the frontoparietal cortex compared with normal subjects. There was a significant difference in the NAA/Cho in the frontoparietal lobe between CBD and PSP patients. Conclusion: 1H-MRS may indicate different regional patterns of neuronal involvement in CBD and PSP. We suggest that this could be helpful in the differentiation and diagnostic evaluation of CBD and PSP patients.

Some patients with cervical disc herniation suffer from persistent nuchal pain and muscle spasms after decompressive surgery despite the lack of clinical and radiological signs for actual spinal root compression. Sonographic examination of the brain in some of these patients showed increased echogenicity of the lentiform nuclei as described in patients with idiopathic dystonia. This has been linked to an altered Menkes protein level and copper metabolism. We suggest a relationship between persistent nuchal pain after adequate cervical disc surgery and dystonic movement disorders. Thirteen patients with persistent nonradicular nuchal pain after at least one cervical disc surgery and without evidence of continuing spinal root compression and 13 age-matched controls were included. All patients had a complete neurological examination, ultrasound, and MRI scan of the brain. In addition, Menkes protein mRNA levels of leucocytes were analyzed in patients and controls. All patients with persistent nuchal pain exhibited a constant tonic unilateral shoulder elevation associated with an ipsilateral hypertrophy of the trapezius muscle. Ultrasound examination showed an increased echogenicity of the lentiform nucleus in one patient unilaterally and in 10 patients bilaterally but in none of the controls. On MRI the T2-values of the lentiform nuclei were found to be higher in patients exhibiting a hyperechogenicity of the lentiform nuclei compared to controls (P = 0.01). In addition, Menkes protein mRNA levels were decreased in patients with cervical disc herniation (P = 0.03). Clinical, neuroimaging, and biochemical findings of this selected patient sample with chronic nuchal pain and muscle spasms after cervical disc surgery resemble alterations in patients with idiopathic cervical dystonia. This suggests a link between both disorders. A peripheral trauma to the nerve roots may precipitate dystonic movements in susceptible patients and chronic dystonic muscle contraction would account for the persistent nuchal pain.

Background: The aim of the present paper was to determine anatomical brain damage causing parkinsonism in patients with subcortical arteriosclerotic encephalopathy. Methods: Using magnetic resonance imaging, the findings in 16 subcortical arterio-sclerotic encephalopathy patients with parkinsonism were compared with those of 16 subcortical arteriosclerotic encephalopathy patients without parkinsonism. In addition to conventional magnetic resonance imaging, the magnetization transfer technique was also employed, and the magnetization transfer ratios of white matter hyperintensity lesions in the frontal lobe were measured to detect structural changes. Results: The extent of infarcted lesions in the lentiform nucleus of patients with parkinsonism was significantly greater than in patients without parkinsonism. Although white matter hyperintensity areas did not differ significantly between the two patient groups, magnetization transfer ratios in the white matter hyperintensity lesions of patients with parkinsonism were significantly lower than those of patients without parkinsonism. The lower magnetization transfer ratios suggest that tissue damage of white matter lesions in patients with parkinsonism is more severe than in patients without it. Conclusion: Both severe tissue damage in the frontal white matter and extensive infarcted lesions in the lentiform nucleus might be responsible for the development of parkinsonism in patients with subcortical arteriosclerotic encephalopathy.

Proton magnetic resonance spectroscopy, localized to the lentiform nucleus, was carried out in nine patients with a clinical diagnosis of Steele-Richardson-Olszewski syn drome (SRO) and in eight healthy ape-matched controls. Three of the nine SRO patients had a so-called ''eye of the tiger sign'' with high signal in the globus pallidus surrounded by a ring of low signal on T2 weighted magnetic resonance imaging previously only reported in Hallervorden-Spatz disease. One of these patients had pathologically proven SRO at postmortem. The SRO group showed a significant reduction in the median concentration from N-acetyl groups (median, 6.87 mM; range, 4.92-10.59 mM; p < 0.015) compared with the control group (median, 9.85 mM; range, 9.26-11.0 mM). The N-acetylaspartate concentration was significantly reduced in seven of the nine patients studied. The reduction of the N-acetylaspartate-creatine ratio from the lentiform nucleus in the SRO group may reflect neuronal loss, occurring predominantly in the globus pallidus. Proton magnetic resonance spectroscopy may be a useful, noninvasive technique to help differentiate the various parkinsonian syndromes.

Background and purpose Drug-induced parkinsonism usually resolves after discontinuation of the causative agent. However, it persists in some patients, who actually have subclinical neurodegenerative parkinsonism. Identification of this condition is important because these patients could benefit from therapeutic measures. The objective of this study was to prove whether transcranial sonography, a technique used in the diagnosis of neurodegenerative parkinsonism, can be used for the said identification. Methods In this prospective study, patients with drug-induced parkinsonism were followed for at least 6 months after discontinuation of the causative drug and performance of blinded transcranial sonography. Patients were categorized as having iatrogenic parkinsonism if the clinical presentation had resolved or subclinical drug-exacerbated parkinsonism if it persisted. Once the patient was classified into one of the two groups, an expert assessed the transcranial sonography findings and their agreement with the clinical diagnosis. Results Twenty patients composed the group for analysis of results. Assessing hyperechogenicity in the substantia nigra >20 mm2 and/or hyperechogenic lentiform nucleus, differences were detected between the iatrogenic parkinsonism and the subclinical drug-exacerbated parkinsonism groups, although they did not reach statistical significance (Fisher's exact test 0.09). Joint assessment of sonographic alterations in both structures had a negative predictive value of 85.7% for diagnosis of drug-induced parkinsonism, with a negative likelihood ratio of 0.3. Conclusions Although in our study statistically significant differences were not found between the transcranial sonography characteristics of subclinical drug-exacerbated parkinsonism and iatrogenic parkinsonism patients, we believe that transcranial sonography is a valid technique for diagnosis of drug-induced parkinsonism.

Regional cerebral blood flow (rCBF) was measured with H 2 15 O positron emission tomography in 5 patients with acquired hemidystonia (AHD) due to structural lesions of the basal ganglia or posterior thalamus contralateral to the dystonic limb. Patients were scanned at rest and when performing paced joystick movements in freely chosen directions with the dystonic and then the unaffected arm. Findings were compared with those of 5 age-matched controls performing joystick movements with the right arm. At rest, there was decreased activity in ventroanterior thalamus, posterior thalamus, angular gyrus ipsilateral to the lesion, and bilateral frontoorbital cortex. At a similar level of significance, increased resting activity was found in lentiform nucleus, hippocampus, and anterior insula contralateral to the lesion. Using the affected arm, AHD cases showed significant overactivity of contralateral prefrontal, lateral premotor cortex, rostral supplementary motor area, anterior cingulate area 32, bilateral sensorimotor cortex (SMC) and insula, mesial parietal cortex, and ipsilateral cerebellum. There was similar frontal overactivity when the unaffected arm performed the joystick movements, though SMC and insula overactivity was contralateral rather than bilateral. The associated frontal overactivity on movement is consistent with acquired dystonia being a syndrome of thalamofrontal disinhibition due to structural disruption of basal ganglia inhibitory control. Our findings also suggest that cortical activation during movement of the unaffected limb is abnormal in acquired hemidystonia.

Proton magnetic resonance spectroscopy, localized to the lentiform nucleus, was carried out in 7 patients with the pure or predominantly striatonigral variant (SND) of multiple system atrophy (MSA), 5 patients with the olivopontocerebellar variant of MSA, 9 patients with a clinical diagnosis of idiopathic Parkinson's disease (IPD), and 9 healthy age-matched controls. The MSA group with predominantly striatonigral involvement showed a significant reduction in the N-acetylaspartate (NAA)/creatine ratio (median, 1.19; range, 0.96-2.0; p0.02) compared with the NAA/creatine ratio from the control group (median, 1.76; range, 1.61-2.0). In contrast, the IPD group had a normal NAA/creatine ratio (median, 1.82; range, 1.19-2.31; p0.05). The NAA/creatine ratio was markedly reduced in 6 of the SND patients and in only 1 IPD patient. The choline/creatine ratio was also significantly lower in the SND group (median, 1.02; range, 0.91-1.23; p0.04) compared with the control group (median, 1.22; range, 1.05-1.65). The IPD group showed a normal lentiform choline/creatine ratio (median, 1.13; range, 0.89-1.65; p = 0.25) compared with controls. The olivopontocerebellar group also showed a significant reduction in the NAA/creatine ratio from the lentiform nucleus (median, 1.47; range, 1.22-1.68; p0.01) compared with the controls as well as a nonsignificant reduction in the choline/creatine ratio (median, 0.93; range, 0.85-1.27; p0.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Four patients with a stroke developed micrographia. In two patients, the condition was pure and in the two other patients it was associated with signs of writer's cramp. We conclude that infarct of the left lenticular nucleus could either mimic pure micrographia similar to that of Parkinson's disease or micrographia associated with dystonia. © 2002 Movement Disorder Society

Infantile spasms are generalized seizures specific to early infancy, and are believed to result from complex cortical-subcortical interactions during a critical period of development. We used positron emission tomography (PET) to determine local cerebral metabolic rates for glucose (1CMRG1c) in 44 infants with spasms, in an attempt to define the neuroanatomical substrates that mediate these seizures. All infants were studied in the awake state during continuous electroencephalographic monitoring. The most consistent abnormality on PET, seen in 32 infants, was the symmetrical increase in 1CMRG1c in the lenticular nuclei, compared to age-matched normal infants (p less than 0.05). In 21 infants, even though the brain stem appeared to be visually more prominent compared to normal infants, statistically significant differences could not be demonstrated. Relative hypermetabolism of the lenticular nuclei (1) occurred irrespective of whether the spasms were cryptogenic or symptomatic, (2) was associated with focal cortical hypometabolism in 22 and focal cortical hypermetabolism in 5 of the 44 infants, and (3) was not characterized by any specific electroencephalographic abnormality during PET. These findings suggest that the lenticular nuclei may contribute to the pathophysiological state that predisposes to infantile spasms, and is consistent with the observation that spasms are clinically symmetrical even when focal cortical lesions are present. A scheme describing the neuronal circuitry likely to be involved in the generation of infantile spasms is proposed.

Four patients with clinical and serologically proven Herpes Simplex Encephalitis (HSE) were examined by Magnetic Resonance Imaging (MRI) following Computed Tomographic (CT) scans. MRI proved more sensitive at detecting the temporal lobe abnormalities than CT and invariably showed the lesions to be more extensive than suspected. The findings were consistent with an acute inflammatory process. Haemorrhage was present in only one patient. The sharp transition to normal at the lentiform nucleus previously described on CT was present in only one of the four patients, but was observed in a different patient with cerebral lymphoma and no evidence of HSE and is thus concluded to be less specific than previously thought. A repeat MRI scan at seven months on one of the patients showed persisting increased signal on T2 weighted images after resolution of the mass effect. The pathology and suspected mechanisms for the MRI appearances are discussed. MRI is concluded to be a valuable tool in the early diagnosis of HSE and in the longer term for further evaluation of residual disabilities.

Purpose: In this study we utilized resting state fMRI (rsfMRI) to identify and compare hypothalamic connectivity in lean subjects during fasting and satiated state. Methods: rsfMRI were performed on 7 healthy lean subjects (4 male, 3 female, 20–35 yo, BMI = 18–25 kg/m2). Subjects fasted overnight (8 hrs), average blood glucose of 80± 5 mg/dL. None of the subjects were on diet program or recently lost/gain weight. rsfMRI EPI parameters:TR = 3000ms, TE = 30 ms, and spatial resolution of 1.7 × 1.7 mm × 5mm, ST= 65 mins (10‐min pre‐glucose ingestion acquisition, followed by 50 mins of post‐glucose ingestion). During rsfMRI, subjects ingested standard glucola (75 g of glucose dissolved in 296 ml of flavored water) over 4.5 ± 0.75 min via a peroral rubber tube. Preprocessing procedure was implemented using FSL consisting of 1) motion correction 2) spatial smoothing, 3) temporal filtering between 0.01–0.08 Hz. Using the Talairach‐Daemon atlas, ROI in the hypothalamus was selected. The individual timeseries of hypothalamus was used as seed to find neural structures that share similar temporal pattern that hypothalamus. Results: Structures that were engaged only during fasting were (Table 1): Inferior frontal gyrus (BA 47) has been linked to the modulation of hunger. The output from the orbitofrontal cortex to both striatum (lentiform nucleus) and lateral hypothalamus has been reported. The structures that were engaged only during satiated state were: Superior temporal gyrus has been implicated in food inhibition and mid temporal gyrus has been reported to be engaged in satiation. Cerebellum is activated when the brain is monitoring its sensory systems.

An atlas of transverse sections of the globus pallidus and striatum was established in macaque with reference to ventricular coordinates. The three-dimensional geometry of the striato-pallidal complex was investigated by means of sagittal and horizontal reconstructions. Both a personal case studied with autoradiography and data from literature were used to analyze the distribution of cortical axons into the striatum. One may distinguish two striatal territories: one, somatotopically arranged, sensorimotor territory extending over the major part of the putamen; and the other, an associative territory, comprising the caudate nucleus and antero-medial and postero-inferior parts of the putamen. The striato-pallido-nigral bundle was studied using Golgi, Perls, and Fink-Heimer techniques. The bundle is described in four parts: prepallidal (subdivided into caudato-pallidal and putamino-pallidal subparts), transpallidal, pallido-nigral, and nigral. The tracing of the limit between the caudate (associative) and putaminal (essentially sensorimotor) territories shows that the two components are of roughly the same size in the pallidum. The data were compared with geometry and orientation of the dendritic arborizations of large pallidal neurons analyzed in Yelnik et al. ('84). Each pallidal dendritic disc is able to receive axons from a wide region of the striatum. This leads to a convergence on pallidal neurons of striatal axons from different striatal somatotopic strips and from the sensorimotor and associative territories. This is an indication that the globus pallidus may have an integrative role.

Ictere nucleaire et meningite bacterienne sont devenus rares. 4 types de lesions sont toujours observees malgre les efforts des neonatalogistes: les hemorragies de la zone matricielles, la leucomalacie periventriculaire, la gliose de la substance blanche, la necrose du thalamus avec ou sans necrose du striatum ou du noyau lenticulaire

Utilizing the horseradish peroxidase retrograde tracing technique and the 2-deoxy-D-glucose metabolic mapping technique, we have demonstrated in chickens the distribution of retinal ganglion cells that project to the lentiform nucleus of the mesencephalon (LM) and the retinotopic organization of the projection in the LM. Retinal ganglion cells labeled after a nearly complete injection into the LM were found in the four quadrants, distributed in a wide horizontal belt lying along both sides of the retinal equator and stretching from the temporal to the nasal retina. The HRP-labeled cells, which appeared round or oval, ranged from 25 to 840 micron 2 in size with most in the smaller size range. Results of partial HRP injections into the LM and metabolic mapping patterns in the LM produced by stimulation of half the retina with horizontal visual motion suggest that there is an orderly mapping of the retina onto the LM. The inferior temporal quadrant projects to the rostrodorsal LM; the inferior nasal quadrant projects to the caudodorsal LM. The superior temporal quadrant projects to the middle and ventral LM, extending from the rostral to the caudal pole, whereas the superior nasal quadrant projects to a small zone in the caudal LM. The mapping of the retinal quadrants in the LM is remarkably similar to that reported in the optic tectum of birds. We suggest that a common embryological anlage with the optic tectum and the arrangement of retinal axons in the optic tract are important factors in establishing the retinotopic organization of the LM.

The projection of ventral pallidal neurons to the mediodorsal nucleus of the thalamus (MD) was examined in rats by combined retrograde transport of horseradish peroxidase (HRP) after injections in the MD and glutamate decarboxylase (GAD) immunocytochemistry at light and electron microscopic levels, with and without prior exposure of the brains to colchicine. HRP was transported to the soma of medium-sized and large ventral pallidum neurons, which along with their long, large dendrites were contacted by many glutamate decarboxylase immunoreactive synaptic boutons. The retrograde tracer positive neurons bore a remarkable resemblance to the projecting cells of the globus pallidus and entopeduncular nucleus. When colchine exposure was included in the tissue preparation, some but not all tracer positive cells also exhibited cytoplasmic GAD immunoreactivity.

Previous histological and histochemical studies have provided evidence that the globus pallidus (external pallidal segment) as conventionally delineated in the rat extends ventrally and rostrally beneath the transverse limb of the anterior commissure, invading the olfactory tubercle with its most ventral ramifications. This infracommissural subdivision of the globus pallidus or ventral pallidum (VP) is most selectively identified by being pervaded by a dense plexus of substance-P-positive striatofugal fibers; the extent of this plexus indicates that the VP behind the anterior commissure continues dorsally over some distance into the anteroventromedial part of the generally recognized (supracommissural) globus pallidus; the adjoining anterodorsolateral pallidal region, here named dorsal pallidum (DP), receives only few substance-P-positive fibers, but contains a dense plexus of enkephalin-positive striatal afferents that also pervades VP. Available autoradiographic data indicate that VP and DP receive their striatal innervation from two different subdivisions of the striatum: whereas VP is innervated by a large, anteroventromedial striatal region receiving substantial inputs from a variety of limbic and limbic-system-associated structures (and therefore called "limbic striatum"), DP receives its striatal input from an anterodorsolateral striatal sector receiving only sparse limbic afferents ("nonlimbic" striatum) but instead heavily innervated by the sensorimotor cortex. The present autoradiographic study has produced evidence that this dichotomy in the striatopallidal projection is to a large extent continued beyond the globus pallidus: whereas the efferents of DP were traced to the subthalamic nucleus and substantia nigra, those of VP were found to involve not only the subthalamic nucleus and substantia nigra but also the frontocingulate (and adjoining medial sensorimotor) cortex, the amygdala, lateral habenular and mediodorsal thalamic nucleus, hypothalamus, ventral tegmental area, and tegmental regions farther caudal and dorsal in the midbrain. These findings indicate that the ventral pallidum can convey striatopallidal outflow of limbic antecedents not only into extrapyramidal circuits but also back into the circuitry of the limbic system.

The present paper is a Golgi study, with high-power lenses, of the primate globus pallidus. Two kinds of inconstant processes of large neurons are first described: complex endings and thin processes. Complex endings are thick apparatuses terminally located on dendrites having many appendages of various types. Contacts were observed not only between striatal axons and these complex endings but also between complex endings and the soma, dendritic stems, dendritic portions or complex endings of other large pallidal neurons. Thin processes were usually beaded, very thin, and arose from any part of the dendritic tree. Contacts were seen between them and soma or dendrites of other large neurons. These thin processes were very similar to initial axonal collaterals and together constitute a common pool of processes. Complex endings and thin processes were essentially observed in the lateral nucleus of the pallidum where they apparently are evenly distributed inside the nucleus but randomly distributed on individual neurons. Two neuronal types other than large pallidal neurons were isolated: the smallest were considered to be local circuit neurons, while intermediate-sized neurons might be the origin of a particular efference. Many striatal axons gave no branches over long distances and collaterals were of two types and most frequently were short (less than 50 micron). Larger axonal arborization were rarely encountered. In addition to parallel contacts, numerous very short ones were observed. All these contacts between striatal axons and dendrites of large pallidal neurons seem to be irregularly distributed.