Frontotemporal Hypometabolism Research Articles

Clinical and neuroimaging characterization of the first frontotemporal dementia family carrying the MAPT p.K298E mutation

We present an in-depth clinical and neuroimaging analysis of a family carrying the MAPT K298E mutation associated with frontotemporal dementia (FTD). Initial identification of this mutation in a single clinical case led to a comprehensive investigation involving four affected siblings allowing to elucidate the mutation's phenotypic expression.A 60-year-old male presented with significant behavioral changes and progressed rapidly, exhibiting speech difficulties and cognitive decline. Neuroimaging via FDG-PET revealed asymmetrical frontotemporal hypometabolism. Three siblings subsequently showed varied but consistent clinical manifestations, including abnormal behavior, speech impairments, memory deficits, and motor symptoms correlating with asymmetric frontotemporal atrophy observed in MRI scans.Based on the genotype–phenotype correlation, we propose that the p.K298E mutation results in early-onset behavioral variant FTD, accompanied by a various constellation of speech and motor impairment.This detailed characterization expands the understanding of the p.K298E mutation's clinical and neuroimaging features, underlining its role in the pathogenesis of FTD. Further research is crucial to comprehensively delineate the clinical and epidemiological implications of the MAPT p.K298E mutation.

Altered brain metabolism in frontotemporal dementia and psychiatric disorders: involvement of the anterior cingulate cortex

BackgroundBehavioural symptoms and frontotemporal hypometabolism overlap between behavioural variant of frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD), hampering diagnostic distinction. Voxel-wise comparisons of brain metabolism might identify specific frontotemporal-(hypo)metabolic regions between bvFTD and PPD. We investigated brain metabolism in bvFTD and PPD and its relationship with behavioural symptoms, social cognition, severity of depressive symptoms and cognitive functioning.ResultsCompared to controls, bvFTD showed decreased metabolism in the dorsal anterior cingulate cortex (dACC) (p < 0.001), orbitofrontal cortex (OFC), temporal pole, dorsolateral prefrontal cortex (dlPFC) and caudate, whereas PPD showed no hypometabolism. Compared to PPD, bvFTD showed decreased metabolism in the dACC (p < 0.001, p < 0.05FWE), insula, Broca’s area, caudate, thalamus, OFC and temporal cortex (p < 0.001), whereas PPD showed decreased metabolism in the motor cortex (p < 0.001). Across bvFTD and PPD, decreased metabolism in the temporal cortex (p < 0.001, p < 0.05FWE), dACC and frontal cortex was associated with worse social cognition. Decreased metabolism in the dlPFC was associated with compulsiveness (p < 0.001). Across bvFTD, PPD and controls, decreased metabolism in the PFC and motor cortex was associated with executive dysfunctioning (p < 0.001).ConclusionsOur findings indicate subtle but distinct metabolic patterns in bvFTD and PPD, most strongly in the dACC. The degree of frontotemporal and cingulate hypometabolism was related to impaired social cognition, compulsiveness and executive dysfunctioning. Our findings suggest that the dACC might be an important region to differentiate between bvFTD and PPD but needs further validation.

Frontotemporal Hypometabolism in Medication-Induced Tardive Dyskinesia.

Frontotemporal Hypometabolism in Medication-Induced Tardive Dyskinesia.

Cortical metabolic and structural differences in patients with chronic migraine. An exploratory 18FDG-PET and MRI study

BackgroundTo describe interictal brain structural and metabolic differences between patients with episodic migraine (EM), chronic migraine (CM) and healthy controls (HC).MethodsThis is an exploratory study including right-handed age-matched women with EM, CM and HC. On the same day, a sequential interictal scan was performed with 18FDG-PET and MRI. 3D T1-weighted images were segmented with FreeSurfer, normalized to a reference atlas and the mean values of metabolism, cortical thickness (CTh) and local gyrification index (IGI) were determined. Groups were compared using age-adjusted linear models, corrected for multiple comparisons. 18FDG-PET measurements between groups were also analysed adjusting by patient’s age, CTh and lGI. The variables independently associated with diagnosis were obtained using a logistic regression analysis.ResultsFifteen patients (8 EM, 7 CM) and 11 HC were included. Morphometric data showed an increased CTh in 6 frontal areas (L/R-Caudal Middle Frontal, L/R-Rostral Middle Frontal, L-Medial Orbitofrontal and L-Superior Frontal) in CM patients compared to HC without differences for IGI. The structural adjusted analysis in CM showed a statistically significantly hypometabolism in 9 frontal areas (L-Lateral Orbitofrontal, L/R-Medial Orbitofrontal, L-Frontal Superior, R-Frontal pole, R-Parts Triangularis, L/R-Paracentral and R-Precentral) and 7 temporal areas (L/R-Insula, L/R-Inferior temporal, L/R-Temporal pole and R-Banks superior temporal sulcus) compared to HC. EM patients presented intermediate metabolic values ​​between EM and HC (non-significant).ConclusionsCM patients showed frontotemporal hypometabolism and increased frontal cortical thickness when compared to HC that may explain some cognitive and behavioural pain-processing and sensory integration alterations in CM patients. Combined information from sequential or simultaneous PET and MRI could optimize the study of complex functional neurological disorders such as migraine.

Clinical, Imaging, and Pathologic Characteristics of Patients With Right vs Left Hemisphere-Predominant Logopenic Progressive Aphasia.

To assess and compare demographic, clinical, neuroimaging, and pathologic characteristics of a cohort of patients with right hemisphere-predominant vs left hemisphere-predominant logopenic progressive aphasia (LPA). This is a case-control study of patients with LPA who were prospectively followed at Mayo Clinic and underwent [18F]-fluorodeoxyglucose (FDG) PET scan. Patients were classified as rLPA if right temporal lobe metabolism was ≥1 SD lower than left temporal lobe metabolism. Patients with rLPA were frequency-matched 3:1 to typical left-predominant LPA based on degree of asymmetry and severity of temporal lobe metabolism. Patients were compared on clinical, imaging (MRI, FDG-PET, β-amyloid, and tau-PET), and pathologic characteristics. Of 103 prospectively recruited patients with LPA, 8 (4 female) were classified as rLPA (7.8%); all patients with rLPA were right-handed. Patients with rLPA had milder aphasia based on the Western Aphasia Battery-Aphasia Quotient (p = 0.04) and less frequent phonologic errors (p = 0.015). Patients with rLPA had shorter survival compared to typical LPA: hazard ratio 4.0 (1.2-12.9), p = 0.02. There were no other differences in demographics, handedness, genetics, or neurologic or neuropsychological tests. Compared to the 24 frequency-matched patients with typical LPA, patients with rLPA showed greater frontotemporal hypometabolism of the nondominant hemisphere on FDG-PET and less atrophy in amygdala and hippocampus of the dominant hemisphere. Autopsy evaluation revealed a similar distribution of pathologic findings in both groups, with Alzheimer disease pathologic changes being the most frequent pathology. rLPA is associated with less severe aphasia but has shorter survival from reported symptom onset than typical LPA, possibly related to greater involvement of the nondominant hemisphere.

PET‐[18F]UCB‐H for assessing synaptic density in FTD

AbstractBackgroundThe behavioural variant of fronto‐temporal dementia (FTD) is characterized by clinical symptoms including behavioural and cognitive changes and by neurodegenerative involvement of the anterior part of the brain. The objective was to study the in vivo distribution of synaptic loss.Method12 patients with possible FTD and frontotemporal hypometabolism on FDG‐PET (mean disease duration of 4 years) were compared to 12 control participants and 12 patients with Alzheimer’s disease, matched for age, sex and education. Measures of verbal fluency, episodic memory and awareness of cognitive impairment did not differ between patients groups. We used [18F]UCBH‐PET to assess the regional loss of synaptic density. Total distribution volume was obtained with Logan method and carotid artery derived input function. SPM12 was used to analyze pve‐corrected PET and MRI images.ResultA significant decrease of [18F]UCBH uptake was observed in the right anterior parahippocampal gyrus of FTD patients, while atrophy was observed in the ventromedial prefrontal cortex. Loss of synaptic density was observed in the right hippocampus of AD participants, while atrophy extended from the right hippocampus to bilateral posterior associative cortices. AD patients showed lower [18F]UCBH uptake in the precuneus that FTD patients. Anosognosia for clinical symptoms was correlated with synaptic density in caudate nucleus and prefrontal cortex in FTD, and with synaptic density in posterior hippocampus in AD.ConclusionSynaptic loss was predominant in the anterior parahippocampal gyrus of our bvFTD patients. This region is part of the limbic network and the perceptive social brain. A validated measure of anosognosia (a characteristic but variable symptom in bvFTD) was related to synaptic density in two interconnected regions, caudate nucleus and anteromedial prefrontal cortex, the later being involved in self‐reference.

Cortical atrophic-hypometabolic dissociation in the transition from premanifest to early-stage Huntington's disease.

Huntington's disease (HD) is a fatal neurodegenerative disorder with no effective treatment currently available. Although the pathological hallmark of HD is massive striatal atrophy, it has been suggested that cortical deterioration may concomitantly occur and play a major role in the patient's functional independence. Our objective was to characterize cortical structural and metabolic neurodegeneration in the transition from premanifest to early-stage Huntington's disease (HD). Using a surface-based neuroimaging approach, we compared cortical thickness and intracortical FDG-PET uptake in 19 early-symptomatic HD patients with respect to 21 premanifest HD individuals. Early-HD patients showed significant cortical atrophy and intracortical hypometabolism when compared to premanifest subjects (p < 0.05, corrected for multiple comparisons). However, whereas the atrophy pattern was restricted to precentral and parieto-occipital regions, a pronounced frontotemporal hypometabolism was observed. Importantly, structural changes correlated with motor and cognitive performance, and metabolic changes were associated with the presence and severity of apathy in this population, a core neuropsychiatric feature of this disorder. Our findings reveal an asynchronous neuronal loss and metabolic compromise across the cerebral cortex in early HD. Hence, the use of structural and metabolic imaging indicators to characterize disease progression in this population should take into consideration the dissociation which occurs between cortical atrophy and hypometabolism.

Neuropsychiatry in Clinical Practice: The Challenge Of Diagnosing Behavioral Variant Frontotemporal Dementia

The behavioral variant of Frontotemporal dementia (bvFTD) is an insidious neurodegenerative disease associated with progressive degeneration of the frontal lobes, anterior temporal lobes, or both [1]. Alterations in social cognition represent the core symptoms of bvFTD resulting in emotional disengagement and socially inappropriate responses or activities [2,3]. As is apparent in revised consortium criteria, additional neuropsychiatric symptoms including apathy and stereotypical and impulsive behavior are prominent in the clinical presentation [4]. Consequently, both neurodegenerative diseases and primary psychiatric disorders are crucial in the challenging differential diagnosis. The differentiation between bvFTD and Alzheimer’s disease (AD) has become easier by the use of biomarkers that are able to identify underlying AD pathology, such as the amyloid-β (Aβ) and tau [1,5]. However, to distinguish bvFTD from psychiatric disorders can still be difficult, particularly since biomarkers for bvFTD are less robust [6]. Previous studies indicated that as a result of symptomatic overlap between bvFTD and psychiatric disorders, bvFTD patients are clinically often mistaken for psychiatric patients and vice versa [7-10]. The current clinical criteria for bvFTD require that “if behavioral disturbance is better accounted for by a psychiatric diagnosis, a diagnosis of bvFTD has to be excluded” [4]. Despite clinical overlap, bvFTD patients do not often fulfill formal criteria for a psychiatric diagnosis, suggesting that it is valuable to apply formal criteria for psychiatric disorders [11]. Careful clinical phenotyping of overlapping symptoms can help to distinguish bvFTD from psychiatric disorders in clinical practice (Figure 1) [12,13]. Figure 1 Overlap and differentiation between bvFTD and psychiatric disorders in clinical practice. The value of different symptom rating scales and clinical tools has been proven useful in clinical practice in case of suspected bvFTD when a psychiatric disorder is also probable (Figure 2) [11,14,15]. Figure 2 Clinical hallmarks and supportive measuring instruments in the differential diagnosis bvFTD and psychiatric disorders. According to current criteria, the diagnostic certainty of bvFTD increases when Frontotemporal abnormalities are found on neuroimaging. In a large cohort of patients with late-onset behavioral changes, MRI had a sensitivity of 70% and a specificity of 93% for a bvFTD diagnosis [4]. The additional [18F]FDG-PET, when the MRI was inconclusive, had a sensitivity of 90% at the cost of a lower specificity (68%) [16]. [18F]FDG-PET is mainly useful when Frontotemporal hypo-metabolism is absent to exclude bvFTD diagnosis. The interpretation of neuroimaging results should especially be taken with caution in cases with a psychiatric differential diagnosis where [18F]FDG-PET is the only abnormal investigation and in cases with a genetic background where both MRI and [18F]FDG-PET can show a specific abnormalities [16-18]. Genetic screening especially for C9orf72 repeat expansion is emphasized [19,20]. particularly in cases with a remarkable (prolonged) disease course. In clinical practice, bvFTD has a broad differential diagnosis including both neurodegenerative diseases and primary psychiatric disorders. The current criteria for bvFTD have clearly improved diagnostics but differentiating bvFTD from psychiatric disorders remains difficult. The challenge for the next decade is finding specific biomarkers for bvFTD on the one hand, and optimizing the neuropsychiatric diagnosis of bvFTD on the other hand. To this end, patient care for suspected bvFTD patients would be largely improved in a setting where neurologists and psychiatrists work hand in hand, ideally applying a consensus set of clinical rating scales next to their clinical expertise.

Brain positron emission tomography in patients with myotonic dystrophy type 1 and type 2

AimTo determine regions of reduced brain metabolism in patients with myotonic dystrophy type 1 (DM1) and type 2 (DM2) using 18F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and to analyse their potential association with cognitive deficit. MethodStudy included 29 patients (16 DM1 and 13 DM2). FDG-PET and detailed neuropsychological testing were performed in both groups. ResultsThe most common cognitive findings were executive, visuospatial, and naming dysfunction in DM1, and executive and naming dysfunction in DM2. FDG-PET showed the most prominent glucose hypometabolism in prefrontal, temporal, and pericentral regions in both DM1 and DM2 patients, with additional affection of insula and subcortical grey matter in DM2. In DM1 patients, we found association between right frontotemporal hypometabolism and executive dysfunction (p<0.05). In DM2 patients attention deficit was in association with prefrontal, insular, and striatal hypometabolism, as well as right frontotemporal hypometabolism (p<0.05). Executive dysfunction in DM2 was more common in patients with prefrontal and insular hypometabolism, right parietotemporal and frontotemporal hypometabolism, as well as left striatal hypometabolism (p<0.05). Patients with parietotemporal defect on FDG-PET were more likely to have naming dysfunction (p<0.01). ConclusionFDG-PET findings corresponded well with the results of neuropsychological testing. FDG-PET may be a good biomarker of central nervous system involvement in DM1 and DM2, but this hypothesis will have to be more strongly supported by larger studies.

Right Limbic FDG-PET Hypometabolism Correlates with Emotion Recognition and Attribution in Probable Behavioral Variant of Frontotemporal Dementia Patients.

The behavioural variant of frontotemporal dementia (bvFTD) is a rare disease mainly affecting the social brain. FDG-PET fronto-temporal hypometabolism is a supportive feature for the diagnosis. It may also provide specific functional metabolic signatures for altered socio-emotional processing. In this study, we evaluated the emotion recognition and attribution deficits and FDG-PET cerebral metabolic patterns at the group and individual levels in a sample of sporadic bvFTD patients, exploring the cognitive-functional correlations. Seventeen probable mild bvFTD patients (10 male and 7 female; age 67.8±9.9) were administered standardized and validated version of social cognition tasks assessing the recognition of basic emotions and the attribution of emotions and intentions (i.e., Ekman 60-Faces test-Ek60F and Story-based Empathy task-SET). FDG-PET was analysed using an optimized voxel-based SPM method at the single-subject and group levels. Severe deficits of emotion recognition and processing characterized the bvFTD condition. At the group level, metabolic dysfunction in the right amygdala, temporal pole, and middle cingulate cortex was highly correlated to the emotional recognition and attribution performances. At the single-subject level, however, heterogeneous impairments of social cognition tasks emerged, and different metabolic patterns, involving limbic structures and prefrontal cortices, were also observed. The derangement of a right limbic network is associated with altered socio-emotional processing in bvFTD patients, but different hypometabolic FDG-PET patterns and heterogeneous performances on social tasks at an individual level exist.

Parkinsonism-Dementia-ALS Complex (PDA) Phenotype in an African-American Patient (P07.189)

Objective: To report a case of PDA phenotype in an African-American patient. Background Amyotrophic lateral sclerosis (ALS)/Parkinsonism dementia complex (PDC) is an endemic disorder described in patients from Guam and the Kii peninsula of Japan. Patients with this disorder exhibit features of Parkinsonism, akinesia, masked facies, dysarthria, mental slowness, apathy, depression and gait abnormalities and features of ALS. An environmental cause has been suggested. However, recently 4 patients from central Europe were reported to satisfy criteria for PDA, supporting the notion that this complex disorder may not be purely environmental in origin. Design/Methods: Case report. Results: A 59-year old previously healthy, functional African-American man developed progressive cognitive decline over a period of 2 years. The patient was initially found to have subtle memory disturbances, which quickly evolved to an inability to work. Within the next few months, the patient lost his ability to speak, eat and swallow. On neurological exam, the patient was awake and alert, but anarthric, able to follow simple commands. He had normal extra-ocular movements, bifacial diplegia, dysphagia, and positive Glabellar sign. Motor exam showed normal strength, diffuse muscular atrophy, rigidity and bradykinesia. Diffuse hyper-reflexia with sustained ankle clonus, positive jaw jerk reflex, primitive reflexes and frontal release signs were noted. Cerebrospinal fluid evaluation, including 14-3-3, was normal. Brain MRI showed fronto-temporal atrophy. Brain FDG-PET showed fronto-temporal hypometabolism. EMG/NCS revealed diffuse, ongoing denervation in 3 body segments. Conclusions: Here we describe an African-American patient with constellation of signs similar to what has been previously described in PDA patients from Guam/Kii. To our knowledge, this is the first report of a non-Guamanian, non-caucasian patient from the American continent, with PDA, supporting a possible non-environmental, genetic cause. Additional neuropathological and molecular studies will be helpful in analyzing this disease further. Disclosure: Dr. Kassar has nothing to disclose. Dr. Iyadurai has nothing to disclose.

Comparative analysis of brain structure, metabolism, and cognition in myotonic dystrophy 1 and 2

Myotonic dystrophy type 1 and 2 (DM1/DM2) are multisystemic diseases with common cognitive deficits beside the cardinal muscular symptoms. We performed a comprehensive analysis of cerebral abnormalities to compare the neuropsychological defects with findings in different imaging methods in the same cohort of patients. Neuropsychological investigations, structural cerebral MRI including brain parenchymal fraction (BPF) and voxel-based morphometry (VBM), and (18)F-deoxy-glucose PET (FDG-PET) were performed in patients (20 DM1 and 9 DM2) and matched healthy controls, and analyzed using statistical parametric mapping (SPM2). DM1 and DM2 patients showed typical neuropsychological deficits with a pronounced impairment of nonverbal episodic memory. Both patient groups showed a reduction of the global gray matter (measured by BPF), which could be localized to the frontal and parietal lobes by VBM. Interestingly, VBM revealed a bilateral hippocampal volume reduction that was correlated specifically to both a clinical score and episodic memory deficits. VBM also revealed a pronounced change of thalamic gray matter. White matter lesions were found in >50% of patients and their extent was correlated to psychomotor speed. FDG-PET revealed a frontotemporal hypometabolism, independent of the decrease in cortical gray matter. All abnormalities were similar in both patient groups but more pronounced for DM1. Our results suggest that 1) some of the characteristic cognitive deficits of these patients are linked to specific structural cerebral changes, 2) decreases in gray matter and metabolism are independent processes, and 3) the widespread brain abnormalities are more pronounced in DM1.

Combined magnetic resonance imaging and positron emission tomography brain imaging in behavioural variant frontotemporal degeneration: refining the clinical phenotype

In patients with the behavioural variant of frontotemporal dementia, prognosis is often surprisingly good when there is normal structural imaging at presentation. Imaging abnormalities are not, however, mandatory for diagnosis, which in the absence of suitable biomarkers, remains entirely clinical. We aimed to test whether cases with normal structural imaging have hypometabolism suggestive of underlying neurodegeneration, or whether it is likely that such patients are false positive diagnoses of behavioural variant frontotemporal dementia. Patients with this disease (n = 24) and age-matched controls (n = 12) underwent both magnetic resonance imaging (MRI) and quantitative fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning, together with clinical and behavioural assessments. Regions of interest were used to calculate metabolic rate in frontotemporal and control regions. Using a semi-quantitative visual rating scale, patients were divided into MRI-abnormal (n = 15) and MRI-normal groups (n = 9). There was definite frontotemporal hypometabolism in the MRI-abnormal group (particularly in the mesial and orbitofrontal regions) even after accounting for brain volume loss, whereas the MRI-normal group was similar to controls in all regions. In contrast, cognitive and behavioural indices did not separate the two behavioural variant frontotemporal dementia patient groups. The results suggest that the clinical syndrome of the behavioural variant of frontotemporal dementia may not be specific for a neurodegenerative disease, and we hypothesize the existence of a phenocopy. A number of alternative neuropsychiatric and developmental explanations are discussed. We advise caution in diagnosing the illness in patients without imaging abnormalities, and propose that imaging findings are included in criteria for diagnosis.

3.116 Set-shifting deficit and fronto-temporal hypometabolism in early Parkinson's disease

3.116 Set-shifting deficit and fronto-temporal hypometabolism in early Parkinson's disease

Effects of damage to the basal forebrain on brain glucose utilization: a reevaluation using positron emission tomography in baboons with extensive unilateral excitotoxic lesion.

Neuronal loss in the basal forebrain cholinergic structures and frontotemporal hypometabolism are two characteristics of Alzheimer's disease, but their interrelations still are unsettled. We previously reported that unilateral electrolytic lesions of the nucleus basalis of Meynert in baboons were associated with marked but transient cortical hypometabolism. The current study reevaluates this issue using improved methodology. Baboons with unilateral ibotenic acid lesion of all three basal forebrain cholinergic structures (IBO group) were compared with sham-operated animals. The CMRglc was measured with high-resolution coronal positron emission tomography scanning coregistered with magnetic resonance imaging, before surgery and serially between 4 and 72 days afterward. Severe histologic basal forebrain damage and a decrease of more than 50% in cortical choline acetyltransferase activity were found postmortem in the IBO group. Transient and nonspecific hypometabolism was found in the needle track area in both groups. Compared with the sham-operated group, only marginally significant decreases in ipsilateral-contralateral CMRglc ratios were observed in the IBO group, affecting only 1 of 14 neocortical areas investigated (the anterior temporal cortex) at a single postsurgical time (day 14), and the posterior hippocampal region at days 14 and 38. Furthermore, there was no consistently significant correlation between ipsilateral-contralateral CMRglc ratios and cortical choline acetyltransferase activity values in any of the four regions analyzed. These results suggest that cholinergic deafferentation play at best a marginal role in the brain hypometabolism observed in Alzheimer's disease.

FDG-positron emission tomography and invasive EEG: seizure focus detection and surgical outcome.

To study the value of [18F]2-deoxyglucose (FDG)-positron emission tomography when surface ictal EEG is nonlocalizing. FDG-PET scans were performed in 46 patients with complex partial seizures (CPS) not localized by ictal surface-sphenoidal video-EEG (VEEG) telemetry. Interictal PET was performed with continuous EEG monitoring, and images were analyzed with a standard template. Forty patients subsequently had subdural and 6 had depth electrodes (invasive EEG, IEEG); 22 had bilateral implants. A focus was detected in 40, and 35 had temporal lobectomy based on IEEG localization. There was a close association between IEEG and PET localization (p < 0.01): 26 patients had relative unilateral temporal FDG-PET hypometabolism, all had congruent IEEG, and 18 of 23 were seizure-free after temporal lobectomy. Five patients had unilateral frontotemporal hypometabolism (3 of 5 were seizure-free), 1 had frontal hypometabolism, and 14 had no lateralized PET abnormality (4 of 7 were seizure-free). Patients who became seizure-free had significantly higher lateral temporal asymmetry index (AI). PET showed > or = 15% relative temporal hypometabolism (AI) in 12 of 22 patients with nonlateralized surface ictal VEEG and was capable of distinguishing between frontal and temporal foci in 16 of 24 patients with lateralized, but not localized, surface ictal video-EEG. FDG-PET provides valuable data in patients with unlocalized surface ictal EEG and can reduce the number of patients who require IEEG studies. Quantitation is necessary for optimal PET interpretation.

Frontotemporal Hypometabolism in Amyotrophic Lateral Sclerosis‐Dementia Complex

Positron emission tomography (PET) with fluorine‐18‐2‐fluorodeoxyglucose (FDG) showed bifrontal and bitemporal hypometabolism in amyotrophic lateral sclerosis (ALS)‐dementia complex (n = 6; 5 by PET, 4 by postmortem examination) as compared to nondemented ALS (n = 10) and normal subjects (n = 10). Subjects were of comparable age, ALS patients were of comparable motor severity, and those with dementia were either mildly or moderately impaired at the time of PET study. ALS in all patients was of sporadic nature. Results, using Kruskai‐Wallis comparisons, revealed that normalized mean FDG values for the superior frontal and superior and mesial temporal cortical regions in ALS‐dementia patients were diffusely, symmetrically, and significantly lower (p &lt; 0.005) than values from either the normal or the nondemented ALS group. FOG values for the caudate, putamen, lateral temporal cortex, occipital cortex, and cerebellum did not distinguish the groups. Pathological data in 4 ALS‐dementia complex patients revealed significant gross atrophy of gyri in both frontal lobes. The atrophy was less pronounced in the temporal lobes. The striking microscopic finding was an extensive proliferation of reactive astrocytes in the subcortical white matter. ALS‐dementia brains were free of Lewy bodies, Pick bodies, ischemic infarctions, and Alzheimer pathological changes. Neurobehavioral and neuropsychological data in ALS‐dementia patients revealed decrements in psychometricintelligence, memory, orientation aha attention, verbal fluency, concept formation and abstraction, mental speed and flexibility, and expressive language and writing skills, and relatively preserved stereognosis and visuospatial orientation.