Frontal Lobe Type Research Articles

Hypometabolic patterns of focal cortical dysplasia in PET-MRI co-registration imaging: a retrospective evaluation in a series of 83 patients.

To characterize the PET-MRI co-registration of hypometabolic patterns in focal cortical dysplasia (FCD) types I and II and provide some suggestions in presurgical evaluation of epilepsy surgery. We retrospectively analyzed PET-MRI co-registration imaging data from a cohort of 83 epilepsy patients with histologically confirmed FCD types I and II. Hypometabolic patterns were classified into 4 types: bottom of sulcus hypometabolism (BOSH), single island of sulcus hypometabolism (SIOS), single gyrus or sulcus hypometabolism (SGOS), and multiple gyri and sulci hypometabolism (MGOS). Most of cases that were overlooked by conventional MRI and PET evaluation but positive in PET-MRI co-registration were focalized lesions in dorsolateral frontal lobe (9/15) and FCD type IIa was the most prevalent pathological type (11/15). The FCD histological types (p = 0.027) and locations (p < 0.001) were independent predictors of PET-MRI co-registration hypometabolic patterns. Focalized hypometabolic patterns (BOSH, SIOS, SGOS) were primarily observed in the frontal lobe (33/39) and FCD type II (43/62) and extensive pattern (MGOS) in temporal lobe (18/20) and FCD type I (16/21; p < 0.005). PET-MRI co-registration enhanced the detection of FCD type IIa compared with conventional MRI and PET reading. The hypometabolic patterns of FCD type I and temporal lobe FCD were more extensive than those of FCD type II and frontal lobe FCD, respectively. The predilection of focalized hypometabolic patterns in frontal lobe FCD suggested that subtle lesions should be checked carefully in patients with suspected frontal lobe epilepsy.

Influence of Mild White Matter Lesions on Voxel-based Morphometry

Purpose:The aim of this study was to investigate whether the detectability of brain volume change in voxel-based morphometry (VBM) with gray matter images is affected by mild white matter lesions (MWLs).Methods:Three-dimensional T1-weighted images (3D-T1WIs) of 11 healthy subjects were obtained using a 3T MR scanner. We initially created 3D-T1WIs with focal cortical atrophy simulated cortical atrophy in left amygdala (type A) and the left medial frontal lobe (type B) from control 3D-T1WIs. Next, the following three types of MWL images were created: type A + 1L and type B + 1L images, only one white matter lesion; type A + 4L and type B + 4L images, four white matter lesions at distant positions; and type A + 4L* and type B + 4L* images, four white matter lesions at clustered positions. Comparisons between the control group and the other groups were performed with VBM using segmented gray matter images.Results:The gray matter volume was significantly lower in the type A group than in the control group, and similar results were observed in the type A + 1L, type A + 4L, and type A + 4L* groups. Additionally, the gray matter volume was significantly lower in the type B group than in the control group, and similar results were observed in the type B + 1L, type B + 4L, and type B + 4L* groups, but the cluster size in type B + 4L* was smaller than that in type B.Conclusion:Our study showed that the detectability of brain volume change in VBM with gray matter images was not decreased by MWLs as lacunar infarctions. Therefore, we think that group comparisons with VBM should be analyzed by groups including and excluding subjects with MWLs, respectively.

Orbitofrontal and Insular Epilepsy

Orbitofrontal and insular epilepsy are difficult to recognize because clinical presentations are variable and surgical approaches remain difficult. Literature review and review of our own case series including selected cases regarding the clinical manifestation and diagnostic utility of diagnostic tests in orbitofrontal and insular epilepsy. Orbitofrontal epilepsy presents with either frontal lobe type seizures with hypermotor automatism or temporal lobe type seizures with oroalimentary and manual automatisms depending on the spread pattern. Ictal single photon emission computed tomography (SPECT) and other functional imaging can be helpful, but intracranial electroencephalograms (EEGs) are still required to identify orbitofrontal seizure onset. Insular epilepsy presents with throat constriction and unilateral paresthesias. Preoperative functional imaging methods can be helpful, but exploration of the insula is required to identify unequivocal insular onset. Intracranial EEG in the insula can be performed safely and should be considered in atypical temporal lobe cases. Intracranial EEG remains the main diagnostic modality to identify orbitofrontal and insular epilepsy. Newer diagnostic modalities such as high-frequency oscillations, EEG, functional magnetic resonance imaging (fMRI), magnet resonance spectroscopy, and magnet source imaging need to be examined further to establish their diagnostic utility.

Altered microstructural connectivity in juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is characterized by myoclonic jerks of the upper limbs, often triggered by cognitive stressors. Here we aim to reconcile this particular seizure phenotype with the known frontal lobe type neuropsychological profile, photosensitivity, hyperexcitable motor cortex, and recent advanced imaging studies that identified abnormal functional connectivity of the motor cortex and supplementary motor area (SMA). We acquired fMRI and diffusion tensor imaging (DTI) in a cohort of 29 patients with JME and 28 healthy control subjects. We used fMRI to determine functional connectivity and DTI-based region parcellation and voxel-wise comparison of probabilistic tractography data to assess the structural connectivity profiles of the mesial frontal lobe. Patients with JME showed alterations of mesial frontal connectivity with increased structural connectivity between the prefrontal cognitive cortex and motor cortex. We found a positive correlation between DTI and fMRI-based measures of structural and functional connectivity: the greater the structural connectivity between these 2 regions, the greater the observed functional connectivity of corresponding areas. Furthermore, connectivity was reduced between prefrontal and frontopolar regions and increased between the occipital cortex and the SMA. The observed alterations in microstructural connectivity of the mesial frontal region may represent the anatomic basis for cognitive triggering of motor seizures in JME. Changes in the mesial frontal connectivity profile provide an explanatory framework for several other clinical observations in JME and may be the link between seizure semiology, neurophysiology, neuropsychology, and imaging findings in JME.

Is the pathology of corticobasal syndrome predictable in life?

Corticobasal syndrome (CBS) has been associated with a heterogeneous spectrum of pathologies with an increasing number of reports of Alzheimer's type pathology. There is, however, no means of predicting pathology of CBS in vivo at present. We compared the clinical features of patients presenting with CBS who have either pathologic changes of classic corticobasal degeneration (CBD) or Alzheimer's disease (AD) at post-mortem to identify predictors of the specific pathological processes in life. Twelve patients with CBS were followed prospectively; six had AD and six had classic CBD neuropathology. After review of the presenting clinical features, we identified nine potential predictor variables, compared their frequency in the two groups, and performed a discriminant function analysis. Initial episodic memory complaints and poor performance on the combined orientation-memory subtest of the Addenbrooke's Cognitive Examination (ACE) reliably predicted AD pathology while varying combinations of early frontal-lobe type behavioral symptoms, nonfluent language disturbance, orobuccal apraxia, and utilization behavior predicted CBD pathology ante-mortem. CBS is frequently associated with Alzheimer's disease pathology. Early episodic memory impairment versus early behavioral symptomatology appears to best predict AD or CBD pathology in life.

Adult onset cerebral form of X-linked adrenoleukodystrophy with dementia of frontal lobe type with new L160P mutation in ABCD1 gene

X-linked adrenoleukodystrophy is a genetically determined disorder that causes varying degrees of malfunction of the adrenal cortex and central nervous system and is characterized by abnormally high levels of very long chain fatty acid in tissues and body fluids. The gene ABCD1, responsible for X-ALD, has been mapped on chromosome Xq28. More than 500 different mutations have been reported but no correlation between genotype and phenotype has been found. To investigate the occurrence of known or new mutations in the ABCD1 gene in patients with clinically and biochemical proven adrenoleukodystrophy. A 37-year-old patient with history of one-year progression of personality and behavioral changes such as, fluctuation of apathy and euphoria, perseveration, bizarre affect, and general disengagement, preliminarily assessed as adrenoleukodystrophy has undergone a clinical, biochemical and genetic examination in order to confirm the diagnosis and discover a possible mutation. The clinical examination has shown signs of the severe prefrontal syndrome, and a neurological examination disclosed deliberation signs and a spastic quadruparesis predominantly on the lower extremities. MRIs showed confluent hyperintensive lesions in T2 and FLAIR images in both hemispheres with severe progression over 6 to 12 months. Clinical findings referred to adrenoleukodystrophy, consecutively performed genetic analyses showed missense mutation at the codon 479 (T>C) in exon 1 of ABCD 1 gene, predicting the substitution L160P in ALD protein. The same mutation has also been found in patient's mother. We examined a patient with progressive development of early onset frontal lobe type dementia and upper motor neuron signs in which neuroimaging methods and biochemical tests refer to adrenoleukodystrophy. Genetic tests revealed a new mutation at position L160P in ALD protein.

Pathophysiology of Cerebral Circulatory Disorders in Idiopathic Normal Pressure Hydrocephalus

This study was conducted to elucidate the pathologic conditions of cerebral circulatory disorders in idiopathic normal pressure hydrocephalus (iNPH). Among 44 possible iNPH patients, 40 patients underwent shunt surgery based on diagnostic flow charts plotted by the Southern Tohoku method and were evaluated to be shunt-effective at the end of the first post-surgical month. The cerebral blood flow (CBF) was measured by N-isopropyl-((123)I)-P-iodo-amphetamine single photon emission computed tomography (mean, mCBF; cortical region, cCBF; thalamus-basal ganglia region, tbCBF on autoradiography [ARG] method) and the perfusion patterns of the cerebral cortex were measured based on three-dimensional stereotactic surface projection (3D-SSP) Z-score images, before and 1 month after the surgery in all 40 subjects. The mCBF rose significantly from 32.1 +/- 2.74 ml/100 g/min before surgery to 39.8 +/- 3.02 ml/100 g/min after surgery (p < 0.03). Investigation of the change of CBF revealed reductions in the cCBF (3 cases), tbCBF (9 cases), and cCBF + tbCBF (28 cases), with the reduced-cCBF group totaling 31 cases and the reduced-tbCBF group totaling 37 cases. Investigation of cerebral cortex hypoperfusion by 3D-SSP Z-score revealed 31 cases with hypoperfusion (frontal lobe type [19 cases], occipitotemporal lobe type [5 cases], mixed type [7 cases]) and nine cases with cortical normoperfusion (N). The pattern of reduction of the cortical blood flow on ARG method was favorably correlated with the pattern of hypoperfusion of the cerebral cortex on 3D-SSP Z-score images before surgery. A reduction of blood flow was found in the thalamus-basal ganglia region of all N type cases. The blood flow improved in 19 of 31 (61.3%) cases of the reduced-cCBF group and in 32 of 37 (86.5%) cases of the reduced-tbCBF group. All of the cases without detectable improvement exhibited increased blood flow in non-reduction areas. Investigation of the hypoperfusion patterns of the cerebral cortex on 3D-SSP Z-score images, revealed a reduction or disappearance of the hypoperfusion site in 19 of 31 (61.3%) cases, either no-change or a shift of the hypoperfusion site in 12 of 31 (38.7%) cases, and a correlation between the pattern of cortical blood flow reduction on ARG method and the pattern of cerebral cortex hypoperfusion on 3D-SSP Z-score images after surgery. Cerebral circulatory disorders in iNPH manifest as either of two pathophysiological conditions: the "circulatory disorder of the cerebral cortical region" and the "circulatory disorder of the thalamus-basal ganglia region." Various patterns develop according to the disease stage.

Buspirone for Stereotypic Movements in Elderly With Cognitive Impairment

Buspirone for Stereotypic Movements in Elderly With Cognitive Impairment

Cognitive Function and Dissociative Disorder Status Among Veteran Subjects With Chronic Posttraumatic Stress Disorder: A Preliminary Study

Cognitive Function and Dissociative Disorder Status Among Veteran Subjects With Chronic Posttraumatic Stress Disorder: A Preliminary Study

Dementia of frontal lobe type in Kennedy's disease

The pathomorphological correlate of Kennedy's disease (KD) is a degeneration of spinal and bulbar alpha-motor neurons. The disease is caused by a CAG repeat expansion in the first exon of the X-chromosomal androgene receptor gene. Contrary to the common belief that cognitive disorders in motor neuron diseases (MND) are either rare or only mild, there is now an increasing number of case reports on dementia in amyotrophic lateral sclerosis (ALS). In ALS, dementia of the frontal lobe type (frontotemporal dementia, FTD) seems to be the characteristic pattern. However, in KD cognitive dysfunction has not been studied systematically. Here we present a case with clinical characteristics of FTD in a patient with genetically confirmed KD. It remains speculative whether there is an association between KD and FTD comparable to a genetic linkage between ALS and FTD, which has been proposed in recent years. However, we suggest that cognitive dysfunction may be more common in KD than reported until today.

PET findings and neuropsychological deficits in a case of Fahr's disease

In a case of Fahr's disease with frontal lobe type dementia and hyperkinetic-hypotone syndrome, functional changes were investigated using positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) as a tracer. Computed tomography showed bilateral calcifications in the putamen and globus pallidus consistent with the diagnosis of Fahr's disease and a frontally pronounced brain atrophy. In contrast, reduced glucose uptake in PET was not only confined to the areas mentioned above, but extended to the temporal and parietal cortices, bilaterally. These functional changes corresponded to the neuropsychological deficits observed, i.e. disturbed selective attention and cognitive flexibility, verbal perseverations, and declarative memory deficits. It is suggested that functional changes may precede cerebral atrophy in Fahr's disease and may reflect deficits in functional circuits, which involve both the basal ganglia and the frontal, parietal, and temporal lobes.

Clinical concept of frontotemporal dementia.

The clinical concept of frontotemporal dementia is reviewed by discussing its relationships to several related concepts. These include dementia of the frontal lobe type, slowly progressive aphasia without dementia or primary progressive aphasia, semantic dementia and frontotemporal lobar degeneration. A number of examples of confusion in the terminology are also examined.

Heterogeneity of Cerebral Blood Flow: a Fractal Approach

We demonstrate the heterogeneity of regional cerebral blood flow using a fractal approach and single-photon emission computed tomography (SPECT). Tc-99m-labelled ethylcysteine dimer was injected intravenously in 10 healthy controls and in 10 patients with dementia of frontal lobe type. The head was imaged with a gamma camera and transaxial, sagittal and coronal slices were reconstructed. Two hundred fifty-six symmetrical regions of interest (ROIs) were drawn onto each hemisphere of functioning brain matter. Fractal analysis was used to examine the spatial heterogeneity of blood flow as a function of the number of ROIs. Relative dispersion (= coefficient of variation of the regional flows) was fractal-like in healthy subjects and could be characterized by a fractal dimension of 1.17 +/- 0.05 (mean +/- SD) for the left hemisphere and 1.15 +/- 0.04 for the right hemisphere, respectively. The fractal dimension of 1.0 reflects completely homogeneous blood flow and 1.5 indicates a random blood flow distribution. Patients with dementia of frontal lobe type had a significantly lower fractal dimension of 1.04 +/- 0.03 than in healthy controls. Within the limits of spatial resolution of SPECT, the heterogeneity of brain blood flow is well characterized by a fractal dimension. Fractal analysis may help brain scientists to assess age-, sex- and laterality-related anatomic and physiological changes of brain blood flow and possibly to improve precision of diagnostic information available for patient care.

Neurochemical Features of Frontotemporal Dementia

This study examines neurochemical measures of cholinergic, serotonergic and glutamatergic innervation in frontal temporal and parietal cerebral cortex from 16 subjects with frontotemporal dementia (FTD) including 10 subjects with Pick pathology and 6 with dementia of frontal lobe type (DFT) together with 9 subjects with Alzheimer’s disease, and 28 matched controls. In both forms of FTD there was not evidence of any cholinergic abnormality, unlike the situation in AD. Serotonin receptors were lost from frontal and temporal cortex in FTD and from temporal and parietal cortex in AD. In FTD there was no loss of kainate receptors but loss of AMPA receptors from both temporal and frontal lobes. Loss of AMPA receptors differentiated Pick-type FTD from DFT. These results are interpreted to indicate selective losses of subpopulations of cortical pyramidal neurones.

Dementia of the frontal lobe type with clinicopathological features of corticobasal degeneration except for lack of glial cytoskeletal abnormalities

A 60‐year‐old left‐handed lawyer presented with a pro‐gressive dementing, aphasic, and akinetic–rigid syndrome. He later developed stimulus‐sensitive myoclonus, supranuclear gaze palsy, postural finger tremor, and finally, an akinetic‐mute state with contracture of the limbs. Left predominance was evident in the neurological signs and symptoms throughout the course. Corticobasal degenera‐tion (CBD) was clinically suspected. He died of respiratory failure due to repeated aspiration pneumonias 12 years and 7 months after the onset of the disease. The neuro‐pathological examination revealed a right‐dominant hem‐ispheric atrophy, pronounced in the frontal lobes, with numerous ballooned neurons and degeneration in the substantia nigra, corpus striatum, globus pallidus, thal‐amus, inferior olivary nucleus, cerebellum, frontopontine tract and corticospinal tract. While neurofibrillary tangles were sparsely detected in the brain stem, neither Gallyas‐Braak nor tau stainings showed any cytoskeletal abnormalities of glia cells. Our case and previously re‐ported similar cases could belong to a certain category of dementia of the frontal lobe type, such as Pick's disease without Pick's bodies, mimicking CBD both clinically and pathologically. These cases provide essential insight into the concept of CBD and allied disorders.

Psychiatric and behavioral aspects of dementia of the Binswanger type

Binswanger's disease or subacute arteriosclerotic encephalopathy is characterized by diffuse demyelination of the white matter together with lacunar lesions in the basal ganglia and brain stem. Clinically it is a dementing illness associated with vascular riskfactors together with varied clinical and radiological abnormalities. The clinical features of Binswanger's disease are highly variable and the psychiatric and behavioral manifestations have been less well described. Review of the literature together with the study offour cases revealed four symptom-clusters, namely, late-onset paranoid psychosis, confusional state, depression and a behavioral syndrome of the frontal lobe type. However, the symptomatology cannot be regarded as mutually exclusive since features may overlap. The symptoms may precede the intellectual deterioration and motor disturbances that are seen with Binswanger's disease. White matter lesions and, hence, cortical-cortical and cortical-sub-cortical connectivities in the genesis of psychosis, is potentially an interesting topic.

Selective Anterior Cerebral Amyloid Angiopathy and Frontal Lobe Dementia: A Clinicopathologic Correlation

A 77 year old white male with a frontal lobe type of dementia was found to have at autopsy extensive deposition of amyloid in the leptomeningeal blood vessels of the frontal lobe, and to a much lesser degree in the parietal lobe and hippocampus. The temporal and occipital lobes where almost free of amyloid. Parenchymal blood vessels were much less affected. Other striking features included cortical gliosis in the frontal lobe, and the scarcity of amyloid plaques. Neurofibrillary tangles were very rarely encountered in the hippocampus. The dementia could not be fully explained on the basis of Alzheimer's disease, alcohol-related damages or cerebral infarctions. The selective frontal amyloid angiopathy and gliosis may have been related to the dementia.

4-12-04 Dementia of frontal lobe type (DFLT) associated with amyotrophic lateral sclerosis (ALS). First case reported in Cuba

4-12-04 Dementia of frontal lobe type (DFLT) associated with amyotrophic lateral sclerosis (ALS). First case reported in Cuba

Different variants of frontotemporal dementia: a neuropathological and immunohistochemical study

Histological and immunohistochemical findings in 20 cases of frontotemporal dementias-8 cases of dementia of frontal lobe type (DFT), 7 cases of Pick's disease (PD), and 5 cases of motor neuron disease with dementia (MND/D)-are presented. Common features of all three syndromes were: frontotemporal atrophy, involvement of subcortical nuclei, and swollen chromatolytic cells. Ubiquitin (Ub)-positive and tau-negative inclusions in cortical, hippocampal, and motor neurons were found in MND/D and DFT cases, suggesting a common pathogenesis of MND/D and DFT. MND/D showed the same cytoskeletal alterations in motor nuclei as MND without dementia: Bunina bodies and skein-like, Ub-positive inclusions. DFT differed from PD in the preponderance of histopathological changes in upper cortical layers, the sparseness of chromatolytic cells, and the absence of tau-positive Pick bodies (PBs). There were, however, two transitional cases showing Pick-type histology but no PBs, thus linking DFT and PD. PBs expressed chromogranin B and secretoneurin strongly, but chromogranin A only weakly. They were negative for the 70-kDa heat-shock protein, metallothionein, and glutathione-S-transferase.

Generation Effect in Short-Term Verbal and Visuospatial Memory: Comparisons Between Dementia of Alzheimer Type and Dementia of Frontal Lobe Type

Memory deficit is the predominant presenting symptom in dementia. To compare shortterm memory (STM) deficit in early dementia of Alzheimer type (DAT) vs frontal lobe type (DFT), and determine the residual memory capacity for stimulation, the generation effect (the memory advantage of items generated rather than read) was tested on verbal and visuospatial STM in patients with DAT (n =10), DFT (n = 9) and in age-matched normal controls (n = 12). The generation effect enhanced performance in all groups. However, the profile of STM deficit differed in the two dementias: verbal and visuospatial memory were both decreased in DAT vs verbal memory only in DFT. These results provide a further criterion for differentiating between DAT and DFT, and show that memory performance can be enhanced in early dementia using techniques such as the generation effect.