Patterns of cerebral glucose metabolism detected with positron emission tomography differ in multiple system atrophy and olivopontocerebellar atrophy

We used positron emission tomography with [¹⁸F] fluorodeoxyglucose to study local cerebral metabolic rates for glucose (ICMRglc) in patients with multiple system atrophy (MSA), sporadic olivopontocerebellar atrophy (sOPCA), and dominantly inherited olivopontocerebellar atrophy (dOPCA) in comparison with normal control subjects. In MSA, absolute lCMRglc was significantly decreased in the brainstem, cerebellum, putamen, thalamus, and cerebral cortex. In sOPCA, absolute lCMRglc was significantly decreased in the brainstem, cerebellum, putamen, thalamus, and cerebral cortex. In dOPCA, absolute lCMRglc was significantly decreased in the brainstem and cerebellum but not in the other structures. Examination of lCMRglc normalized to the cerebral cortex in comparison with normal controls revealed in MSA significant decreases in the brainstem, cerebellum, and putamen but, in both sOPCA and dOPCA, significant decreases only in the brainstem and cerebellum. The findings indicate that these three disorders all show a marked decrease of lCMRglc in the brainstem and cerebellum but differ in the degree of hypometabolism in forebrain and cerebral cortical structures. The results are consistent with the possibility that, in many cases, sOPCA will evolve into MSA. Moreover, positron emission tomography may provide helpful diagnostic information in these neurodegenerative diseases.     

Speech disorders in olivopontocerebellar atrophy correlate with positron emission tomography findings

We compared the severity of ataxic and spastic dysarthria with local cerebral metabolic rates for glucose (lCMRGlc) in 30 patients with olivopontocerebellar atrophy (OPCA). Perceptual analysis was used to examine the speech disorders, and rating scales were devised to quantitate the degree of ataxia and spasticity in the speech of each patient. lCMRGlc was measured with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET). PET studies revealed marked hypometabolism in the cerebellar hemispheres, cerebellar vermis, and brainstem of OPCA patients compared with 30 control subjects. With data normalized to the cerebral cortex, a significant inverse correlation was found between the severity of ataxia in speech and the lCMRGlc within the cerebellar vermis, cerebellar hemispheres, and brainstem, but not within the thalamus. No significant correlation was found between the severity of spasticity in speech and lCMRGlc in any of these structures. The findings support the view that the severity of ataxia in speech in OPCA is related to the functional activity of the cerebellum and its connections in the brainstem.     

Cerebellar and frontal hypometabolism in alcoholic cerebellar degeneration studied with positron emission tomography

Local cerebral metabolic rate for glucose was studied utilizing 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 14 chronically alcohol-dependent patients and 8 normal control subjects of similar age and sex. Nine of the 14 patients (Group A) had clinical signs of alcoholic cerebellar degeneration, and the remaining 5 (Group B) did not have signs of alcoholic cerebellar degeneration. PET studies of Group A revealed significantly decreased local cerebral metabolic rates for glucose in the superior cerebellar vermis in comparison with the normal control subjects. Group B did not show decreased rates in the cerebellum. Both Groups A and B showed decreased local cerebral metabolic rates for glucose bilaterally in the medial frontal area of the cerebral cortex in comparison with the normal control subjects. The severity of the clinical neurological impairment was significantly correlated with the degree of hypometabolism in both the superior cerebellar vermis and the medial frontal region of the cerebral cortex. The degree of atrophy detected in computed tomography scans was significantly correlated with local cerebral metabolic rates in the medial frontal area of the cerebral cortex, but not in the cerebellum. The data indicate that hypometabolism in the superior cerebellar vermis closely follows clinical symptomatology in patients with alcoholic cerebellar degeneration, and does not occur in alcohol-dependent patients without clinical evidence of cerebellar dysfunction. Hypometabolism in the medial frontal region of the cerebral cortex is a prominent finding in alcohol-dependent patients with or without alcoholic cerebellar degeneration.     

Decreased striatal monoaminergic terminals in olivopontocerebellar atrophy and multiple system atrophy demonstrated with positron emission tomography

We used [¹¹C]dihydrotetrabenazine, a new ligand for the type 2 vesicular monoamine transporter (VMAT2), with positron emission tomography to study striatal monoaminergic presynaptic terminals in 4 patients with multiple system atrophy, 8 with sporadic olivopontocerebellar atrophy, and 9 normal control subjects. Specific binding in the striatum was significantly reduced in the multiple system atrophy patients as compared with the normal control group, with average reductions of 61% in the caudate nucleus (p = 0.002) and 58% in the putamen (p = 0.009). Smaller reductions were found in the sporadic olivopontocerebellar atrophy group, averaging 26% in the caudate nucleus (p = 0.05) and 24% in the putamen (p = 0.11).Mean blood-to-brain [¹¹C]dihydrotetrabenazine transport (K₁) was significantly different between groups only in the cerebellum, with values for the sporadic olivopontocerebellar atrophy group diminished compared with the normal control group. Cerebellar K₁ was not significantly decreased in the multiple system atrophy group. The finding of reduced striatal WT2 in sporadic olivopontocerebellar atrophy patients suggests nigrostriatal pathology, indicating that some may later develop symptomatic extrapyramidal disease.     

Biochemical changes in multiple system atrophy detected with positron emission tomography

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder manifested by parkinsonism and dysfunction of autonomic, cerebellar, urinary, and pyramidal systems. The most frequent presentation is with a combination of parkinsonism and autonomic dysfunction, but cerebellar ataxia with autonomic failure occurs frequently as well. Striatonigral degeneration (SND) and sporadic olivopontocerebellar atrophy (sOPCA) can progress to include autonomic failure and thus may be forms of MSA, but it is not known whether all such cases progress to MSA. Utilizing positron emission tomography (PET) with various ligands, my colleagues and I have investigated the biochemical changes in sOPCA and MSA to understand the relationship between these disorders. An initial study revealed decreased local cerebral metabolic rates for glucose in the brainstem, cerebellum, putamen, thalamus and cerebral cortex in both MSA and sOPCA, suggesting that many sOPCA patients would evolve to develop MSA. Later studies confirmed this by demonstrating decreased monoaminergic nigrostriatal terminals in both sOPCA and MSA patients. The studies suggest that the ligand used might be helpful in determining the risk that an individual patient with sOPCA will progress to develop MSA. An investigation of the course of sOPCA patients observed clinically over several years revealed that approximately one-fourth of them progress to MSA within five years. Studies of gamma-aminobutyric acid type A/benzodiazepine neurotransmitter receptors revealed that these sites are largely preserved in sOPCA and MSA, indicating that symptomatic pharmacological therapy may be possible in these disorders.     

Motor dysfunction in olivopontocerebellar atrophy is related to cerebral metabolic rate studied with positron emission tomography

We compared the severity of motor dysfunction with local cerebral metabolic rates for glucose (lCMRGlc) and the; degree of tissue atrophy in 30 patients with olivopontocerebellar atrophy (OPCA). We devised a scale to quantitate the degree of ataxia in the neurological examinations. lCMRGlc was measured with¹⁸F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET). Tissue atrophy was assessed by visual rating of computed tomographic scans. PET studies revealed Marchked hypometabolism in the cerebellar vermis, cerebellar hemispheres, and brainstem of OPCA patients compared with 30 control subjects. A significant correlation was found between severity of motor impairment and lCMRGlc within the cerebellar vermis, both cerebellar hemispheres, and the brainstem. A significant but weaker relationship was noted between the degree of tissue atrophy in these regions and clinical severity. Partial correlation analysis revealed that motor dysfunction in OPCA correlated more strongly with lCMRGlc than with the amount of tissue atrophy. These results suggest that the clinical manifestations of OPCA are more closely related to the metabolic state of the tissue than to the structural changes in the cerebellum.     

Decreased striatal monoaminergic terminals in multiple system atrophy detected with positron emission tomography.

We examined the density of striatal presynaptic monoaminergic terminals, using a ligand for the type 2 vesicular monoamine transporter, (+)-[11C]dihydrotetrabenazine, with positron emission tomography in 7 normal control subjects, 8 multiple system atrophy (MSA) patients with predominantly parkinsonian features (MSA-P), 8 MSA patients with principally cerebellar dysfunction (MSA-C), and 6 sporadic olivopontocerebellar atrophy (sOPCA) patients. The findings were correlated with the results of neurological evaluations and magnetic resonance imaging studies. Specific binding was significantly reduced in the putamen of all patient groups in the order MSA-P < MSA-C < sOPCA, compared with controls. Mean blood-to-brain ligand transport (K1) was significantly decreased in the putamen of all patient groups and in the cerebellar hemispheres of MSA-C and sOPCA but not MSA-P groups, compared with controls. Significant negative correlations were found between striatal binding and the intensity of parkinsonian features and between cerebellar K1 and the intensity of cerebellar dysfunction. The results suggest fundamental differences between MSA-P and MSA-C groups reflecting differential severity of degeneration of nigrostriatal and cerebellar systems in these two forms of MSA. The findings also show that some sOPCA patients have subclinical nigrostriatal dysfunction and are at risk of developing MSA with disease progression.     

Cerebral hypometabolism in progressive supranuclear palsy studied with positron emission tomography

Progressive supranuclear palsy (PSP) is characterized by supranuclear palsy of gaze, axial dystonia, bradykinesia, rigidity, and a progressive dementia. Pathological changes in this disorder are generally restricted to subcortical structures, yet the type and range of cognitive deficits suggest the involvement of many cerebral regions. We examined the extent of functional impairment to cerebral cortical and subcortical structures as measured by the level of glucose metabolic activity at rest. Fourteen patients with PSP were compared to 21 normal volunteers of similar age using 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography. Glucose metabolism was reduced in the caudate nucleus, putamen, thalamus, pons, and cerebral cortex, but not in the cerebellum in the patients with PSP as compared to the normal subjects. Analysis of individual brain regions revealed significant declines in cerebral glucose utilization in most regions throughout the cerebral cortex, particularly those in the superior half of the frontal lobe. Declines in the most affected regions of cerebral cortex were greater than those in any single subcortical structure. Although using conventional neuropathological techniques the cerebral cortex appears to be unaffected in PSP, significant and pervasive functional impairments in both cortical and subcortical structures are present. These observations help to account for the constellation of cognitive symptoms in individual patients with PSP and the difficulty encountered in identifying a characteristic psychometric profile for this group of patients.     

Contralateral temporal hypometabolism on positron emission tomography in temporal lobe epilepsy

Introduction — No detailed case studies report lateralised hypometabolism on positron emission tomography (PET) contralateral to the epileptogenic focus in temporal lobe epilepsy (TLE). Material and methods — We performed ¹⁸F fluorodeoxyglucose (FDG) PET in two intractable TLE patients. Results — One had right temporal interictal spikes on electroencephalography (EEG) and a right medial temporal lobe lesion on magnetic resonance imaging (MRI). FDG-PET showed decreased uptake in the left temporal lobe. Right temporal ictal onset, with bilateral interictal epileptiform activity, occurred on intracranial EEG. He is seizure free after right temporal lobectomy and ganglioglioma resection. The second had right temporal lobe interictal and ictal EEG activity. MRI demonstrated right anteriomedial temporal increased T2 signal. Neuropsychology revealed bilateral cognitive dysfunction. FDG-PET showed left anterior temporal and lateral frontal hypometabolism. He is seizure free after right temporal lobectomy. Conclusion — These findings suggest that regional uptake asymmetry on FDG-PET may be give misleading lateralising information in TLE.     

Functional imaging with positron emission tomography in multiple system atrophy

Summary. Although the current guidelines for the clinical diagnosis of multiple system atrophy (MSA) do not require structural or functional brain imaging, investigations utilizing positron emission tomography (PET) have been helpful diagnostically in differentiating between MSA and primary autonomic failure; idiopathic Parkinson’s disease; and sporadic olivopontocerebellar atrophy. These investigations have demonstrated different patterns of cerebral glucose utilization and of nigrostriatal projection abnormalities among these disorders and between the cerebellar and parkinsonian forms of MSA. Most of the studies have focused upon patients with well-established disease and none have examined the utility of PET imaging in early stage patients with follow-up of clinical course and autopsy verification to ensure accuracy of diagnosis and to determine the sensitivity and specificity of PET techniques for diagnosis. Recent PET studies have revealed denervation of myocardial post-ganglionic sympathetic neurons in some MSA patients, indicating that this disorder can affect the peripheral autonomic as well as the central nervous system. Investigations utilizing ligands to quantify central nervous system dopaminergic and cholinergic terminals have begun to provide insight into the neurochemical disorders that may underlie two of the sleep disturbances common in MSA, rapid eye movement sleep behavior disorder and obstructive sleep apnea.     

Controlling for cerebral atrophy in positron emission tomography data

This article outlines a simple method for estimating the degree of cerebral atrophy and subsequent experimental control for the effects of cerebral atrophy on regional metabolic values measured with positron emission tomography. It is suggested that rather than correcting derived values for atrophy, less potential error is introduced by experimentally controlling for regional atrophy when possible. By treating the derived metabolic rates and the measure of atrophy as two separate variables, it is also possible to establish whether there actually is a demonstrable relationship between the two measures.     

Cerebral glucose hypermetabolism in Friedreich's ataxia detected with positron emission tomography

Local cerebral metabolic rate for glucose was studied with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 22 patients with Friedreich's ataxia and 23 age-matched normal control subjects. The diagnosis of Friedreich's ataxia was established by the history and physical findings and by excluding other diseases through laboratory investigations. PET studies revealed a statistically significant widespread increase of local cerebral metabolic rate for glucose in the brains of patients with Friedreich's ataxia who were still ambulatory, in comparison with normal control subjects. Nonambulatory patients with Friedreich's ataxia, in comparison with normal control subjects, had significantly increased local cerebral metabolic rates for glucose in the caudate and lenticular nuclei, but not in the other structures studied. The rate was significantly greater in ambulatory patients with Friedreich's ataxia than in nonambulatory patients in all structures studied except the caudate and lenticular nuclei. The data suggest that early in the course of Friedreich's ataxia, the local cerebral metabolic rate for glucose is increased extensively in the central nervous system, and as the disease progresses, it decreases in a regionally specific manner.     

Auditory brainstem response patterns in familial and sporadic olivopontocerebellar atrophy

Auditory brainstem responses (ABR) have been obtained in 22 patients, 15 with familial and 7 with sporadic olivopontocerebellar atrophy; 8 of them were pairs of siblings. ABR abnormalities have been found in 72.7%, with a significant higher percentage in familial versus sporadic patients. Similar ABR patterns have been obtained in affected members of the same family. No correlations have been found between ABR results and the following parameters: age, gender, disease duration, degree of clinical involvement and fashion of inheritance. ABR pattern did not show any modification over a follow-up period of 15-24 months. Our findings suggest that the involvement of the auditory pathways may be under genetic control.     

Correction of positron emission tomography data for cerebral atrophy

Because positron emission tomography (PET) provides measurements per unit volume of intracranial contents, these measurements may be affected by the inclusion of metabolically inactive CSF spaces in the volume in which they are made. Thus, PET measurements of CBF and metabolism may be artifactually lowered in normal aging and dementia, which are both associated with significant brain atrophy. We describe a method to correct global PET data, averaged over several tomographic slices, for cerebral atrophy by using measurements of CSF space volume obtained with quantitative x-ray computed tomography. The importance of making such a correction is demonstrated using PET measurements of CBF and oxygen metabolism obtained in normal young, normal elderly, and demented subjects.     

Occipital hypometabolism demonstrated by positron emission tomography after temporal lobectomy for refractory epilepsy.

BACKGROUND: Epilepsy surgery involves well-planned discrete injury to the brain and may create visual deficits. This study seeks to evaluate the indirect effects of temporal lobectomy on brain metabolism by correlating visual field defects and glucose metabolism in the visual cortex of patients before and after undergoing epilepsy surgery. METHODS: A retrospective survey of 11 patients who had undergone temporal lobectomy for refractory epilepsy in a single institution from 1986 to 1989, and who had pre-lobectomy and post-lobectomy visual field examinations and F-18 2-fluorodeoxyglucose positron emission tomography (FDG-PET) as part of a standard comprehensive epilepsy surgery evaluation. The PET images were analyzed to provide a correlation with the visual field defects that developed after the temporal lobectomy. RESULTS: Occipital hypometabolism in the absence of structural lesions of the occipital lobe was noted in seven patients with contralateral visual field defects and in one of four patients without a visual field defect. FDG-PET studies in three patients repeated for as long as 20 months after lobectomy showed no significant change in the occipital hypometabolism pattern. CONCLUSIONS: Although the occipital cortex was not directly injured during temporal lobectomy, the resulting hypometabolism correlates with the clinical findings of visual field defects. The hypometabolism may be due to deafferentation after interruption of the optic pathways and appears to be persistent.     

橄榄脑桥小脑萎缩脑干听觉诱发电位研究

本文对３５例橄榄脑桥小脑萎缩（ＯＰＣＡ）患者和３９例正常人进行脑干听觉诱发电位（ＢＡＥＰ）检查，结果发现ＯＰＣＡ病人ＢＡＥＰ异常１５例，阳性率４３％，主要异常是Ⅰ～Ⅲ峰间潜伏期延长和Ⅰ～Ⅴ波潜伏期双耳差值增大（Ｐ＜０．０５），提示ＯＰＣＡ主要电生理异常在听神经至桥脑下段之间，此外，还发现脑干电生理异常率与疾病严重程度和ＣＴ脑干萎缩程度有关。     

Infantile spasms: III. Prognostic implications of bitemporal hypometabolism on positron emission tomography

Positron emission tomography (PET) of brain glucose utilization is highly sensitive in detecting focal cortical abnormalities in patients with infantile spasms even when the computed tomographic (CT) and magnetic resonance imaging (MRI) scans are normal. Of 110 infants with spasms evaluated for potential surgical intervention during an 8-year period, we encountered 18 infants (7 males, 11 females; age range, 10 mo to 5 yr) with a common metabolic pattern on positron emission tomography (PET) consisting of bilateral hypometabolism in the temporal lobes. CT and MRI scans did not reveal any focal abnormalities in the 18 infants. Video-electroencephalographic monitoring indicated either bilateral or multifocal epileptogenicity, or failed to show any epileptic focus, so that none of the 18 infants were considered candidates for resective surgery. These patients were then enrolled in a prospective study aimed at determining long-term outcome in the presence of bilateral temporal PET hypometabolism. Analysis of outcome in 14 of the 18 subjects (follow-up period, 10 mo to 10 yr 5 mo; mean, 3 yr 11 mo ± 2 yr 4 mo [SD]) revealed the following: (1) all had severe developmental delay and had failed to gain significant milestones; (2) language development had been minimal or absent; (3) 10 of the 14 met the DSM-IV criteria for autistic disorder. Our findings indicate that patients with infantile spasms and bitemporal glucose hypometabolism on PET comprise a relatively homogeneous group and are typically not candidates for cortical resection. The long-term outcome of these infants is particularly poor and the majority are autistic.