Progressive language disorder associated with frontal lobe degeneration

Abstract

We report a patient KC who presented with a profound disorder of propositional language in association with progressive frontal lobe degeneration. The salient clinical feature was her marked difficulty in responding to open-ended questions, contrasting with the relative preservation of performance on more closed, structured language tasks. Experimental investigations of her language skills revealed significant temporal organizational difficulties. She could generate sentences in sentence completion tasks, although there were errors in thematic role assignment and temporal ordering. She had profound difficulty rearranging written words to form a sentence, despite producing the sentence orally. She was unable to conjoin sentences with an appropriate conjunction. The nature of her language disorder is discussed with reference to traditional categories of aphasia. The case is important in drawing attention to the role of the frontal lobes in language functioning and the potential contribution of processes outside the traditional psycholinguistic categories of phonology, morphology, syntax and semantics. Moreover, KC's clinical presentation falls between that of ‘frontal-lobe’ dementia and ‘progressive aphasia‘, reinforcing the link between those clinical disorders.     

Calcineurin immunoreactivity in striatonigral degeneration

The basal ganglia (including substantia nigra) of two patients with striatonigral degeneration, who had clinical histories of Parkinson's disease, were studied immunohistochemically using a purified antibody to calcineurin (CaN). Marked loss of CaN-immunoreactive neurons in the putamen and neuromelanin-pigmented neurons in the zona compacta of the substantia nigra was seen in both cases. A small number of CaN-immunoreactive neurons remained dispersed in "clusters" or "islands" in the medial portion of the putamen. In one case there was loss of CaN-immunoreactive neurons in the caudate nucleus to a lesser degree than that in the putamen. In addition, both cases showed marked depletion of CaN-immunoreactive afferent nerve fibers in the external and internal segments of the globus pallidus and the zona reticulata of the substantia nigra. This report emphasizes the usefulness of the CaN-immunostaining technique for assessing the striatal efferents in human basal ganglia, and shows the neuropathological changes in the basal ganglia with striatonigral degeneration which were not possible to ascertain with previous techniques.     

Decreased frontal lobe function in people with Internet addiction disorder

In our previous studies, we showed that frontal lobe and brainstem functions were abnormal in online game addicts. In this study, 14 students with Internet addiction disorder and 14 matched healthy controls underwent proton-magnetic resonance spectroscopy to measure cerebral function. Results demonstrated that the ratio of N-acetylaspartate to creatine decreased, but the ratio of cho- line-containing compounds to creatine increased in the bilateral frontal lobe white matter in people with Internet addiction disorder. However, these ratios were mostly unaltered in the brainstem, suggesting that frontal lobe function decreases in people with Internet addiction disorder.     

Frontal lobe tasks do not reflect frontal lobe function in patients with probable Alzheimer's disease

Thirty-one patients with probable Alzheimer's disease (AD) according to NINCDS-ADRDA criteria were psychometrically tested with various frontal lobe tasks. The results were correlated with regional cerebral glucose metabolism (rCMRG1) as measured by positron emission tomography of 18F-2-fluoro-2-deoxy-D-glucose. RCMRG1 of frontal functional-anatomically defined regions was not linked to the performance seen in frontal lobe testing. The majority of the frontal lobe tasks showed a high correlation to severity of dementia that was related to rCMRG1 of the temporo-parietal cortex. There were high intercorrelations of frontal lobe test scores to other tests. Thus, these tasks seem to measure nonspecific cognitive changes in AD patients.     

Decreased cerebral glucose utilization in myotonic dystrophy.

To test the hypothesis that cerebral metabolism is altered in myotonic dystrophy (MyD), we investigated cerebral glucose kinetics and utilization in 11 adult patients with MyD and 14 healthy controls, using 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) and dynamic positron emission tomography. Estimation of rate constants in MyD revealed a reduction of FDG delivery to the brain. Cortical glucose utilization rate was reduced by about 20% in MyD. These findings may be related to the presence of neurologic impairment in MyD and prompt further investigations on the metabolic and clinical features of brain dysfunction in this disease.     

Hippocampal sclerosis dementia differs from hippocampal sclerosis in frontal lobe degeneration

Hippocampal sclerosis (HS) is characterized by selective neuronal loss and gliosis in CA1 and the subiculum and has been associated with several disorders, including Alzheimer’s disease, frontotemporal lobar degeneration with ubiquitin immunoreactive inclusions (FTLD-U), vascular dementia and some tauopathies. In some cases, HS is not associated with other degenerative pathologies. Such cases are sometimes referred to as HS dementia (HSD). Differences between HSD and HS in the setting of FTLD-U have not been systematically investigated. To this end, eight cases of HSD and ten cases of HS associated with FTLD-U were studied with Nissl and periodic acid-Schiff stains to assess neuronal loss and corpora amylacea, respectively. Sections were immunostained with antibodies to glial fibrillary acidic protein, HLA-DR and synaptophysin and immunoreactivity was measured with image analysis in CA1 and the subiculum of each case. Additionally, sections were immunostained with antibodies to 4-R tau to determine the presence of argyrophilic grains. HSD was different from HS associated with FTLD-U. Specifically, it was more common in the elderly, and it was associated with more marked neuronal and synaptic loss and with greater reactive gliosis. Corpora amylacea tended to be more frequent in HSD than in FTLD-U, but there was no difference in frequency of argyrophilic grains. Supported by NIH P50-AG16574, P50-AG25711, P50-NS40256, P01-AG03949.     

Upper motor neuron predominant degeneration with frontal and temporal lobe atrophy

The autopsy findings of a 78-year-old man mimicking primary lateral sclerosis (PLS) are reported. He showed slowly progressive spasticity, pseudobulbar palsy and character change, and died 32 months after the onset of symptoms. Autopsy revealed severe atrophy of the frontal and temporal lobes, remarkable neuronal loss and gliosis in the precentral gyrus, left temporal lobe pole and amygdala, mild degeneration of the Ammon’s horn, degeneration of the corticospinal tract, and very mild involvement of the lower motor neurons. The anterior horn cells only occasionally demonstrated Bunina body by cystatin-C staining, and skein-like inclusions by ubiquitin staining. This is a peculiar case with concomitant involvement in the motor cortex and temporal lobe in motor neuron disease predominantly affecting the upper motor neuron. Received: 18 November 1997 / Revised, accepted: 2 April 1998     

Primate striatonigral projections: A comparison of the sensorimotor-related striatum and the ventral striatum

The striatum receives topographic cortical inputs with the limbic lobe terminating in the ventral striatum and sensorimotor cortical regions terminating in the dorsolateral striatum. The organization of striatonigral projections originating from these different striatal territories was examined in primate by using several anterograde tracers. The ventral striatum innervates a large area of the substantia nigra, including the medial pars reticulata and much of the pars compacta. Moreover, projections from separate areas of the ventral striatum overlap considerably in the substantia nigra. No mediolateral or rostrocaudal topographic order is apparent, and the area of the substantia nigra associated with the ventral striatum is extensive. In contrast, the sensorimotor-related striatum innervates a limited region of the ventrolateral substantia nigra. Similar to ventral striatonigral projections, projections originating from different areas of the sensorimotor-related striatum send converging inputs to the substantia nigra. Sensorimotor-related striatonigral projections avoid the region of the dopaminergic neurons in the dorsal pars compacta. Striatonigral projections from the sensorimotor-related and ventral striatum do not overlap in the substantia nigra. Examination of the outputs of discrete striatal loci indicates that the organization of striatonigral projections is more related to corticostriatal inputs than to a simple rostrocaudal, dorsoventral, or mediolateral tpography of the striatum. Striatal projections that originate from different striatal territories are distinct and nonoverlapping, thus supporting the concept of segregated striatonigral circuits. However, areas of the striatum that receive common cortical inputs send converging inputs to the substantia nigra. This suggests that the substantia nigra is also an important link for integrating information between functionally related (sub)circuits. © 1994 Wiley-Liss, Inc.     

Inhomogeneity of the putaminal lesion in striatonigral degeneration

Summary An immunohistochemical topographic study was carried out in the putamen from three patients with striatonigral degeneration (SND) using antibody to calcineurin (CaN), a neurochemical marker for the striatal medium-size spinous neurons. In patients with SND, there was significant depletion of CaN immunoreactivity in the putamen with the caudal and lateral portion of the putamen being consistently and severely affected. In addition, the SND patients showed an inhomogeneous distribution pattern of residual CaN staining in the putamen, where remaining CaN immunoreactivity appeared as a characteristic patchwork of islands resembling the striosomes observed by the tyrosine hydroxylase or Met-enkephalin immunostaining in the putamen from normal individuals. This finding may account for the fact that there are subregional and compartmental differences in susceptibility of the medium-sized spinous neurons in the putamen with SND.     

Planning impairments in frontal lobe dementia and frontal lobe lesion patients

Patients with frontal lobe brain damage are reportedly impaired on tasks that require plan development and execution. In this study, we examined the performance of 15 patients diagnosed with frontal lobe dementia and 14 patients with focal frontal lobe lesions on the Tower of London planning task. Patients with frontal lobe dementia committed a significantly higher number of rule violations, made more moves, and demonstrated longer solution time latencies compared to their matched controls. Patients with frontal lobe lesions demonstrated significantly delayed solution times and also made more moves compared to their matched controls. Frontal lobe lesion patient performance suggests an impairment in execution-related processes, while frontal lobe dementia patients appear to be impaired in both plan development and execution. Despite these findings, the identification of a specific cognitive impairment that induces these planning problems remains elusive.     

Identification and characterization of frontal lobe degeneration: historical perspective on the development of FTD

This is a historical account of the development of the concept frontotemporal dementia, beginning with our discovery in the late 60s of a simple degenerative form. It was named frontal lobe degeneration of non-Alzheimer type to clearly separate it from the then almost totally dominating diagnosis Alzheimer disease. In the absence of immunohistochemical methods for specific disease markers, we had to rely solely on structural features. Later, from the 80s, the successively introduced methods to show glial acidic protein, tau, synaptophysin, ubiquitin, and other markers confirmed our impression of a simple type of degeneration. These methods also added further forms with additional features, and from the 90s genetics has contributed new disease characteristics, all these advances leading up to the present conceptual structure of frontotemporal lobar degeneration.     

Met-enkephalin immunoreactivity in the basal ganglia in Parkinson's disease and striatonigral degeneration

This study concerns the expression of Met-enkephalin (MEnk) in the striatum and the external segment of the globus pallidus proper (GPe) in normal controls, idiopathic Parkinson's disease (PD), and striatonigral degeneration (SND). For this purpose, we developed a sensitive immunoperoxidase technique to visualize MEnk-positive patches in routinely prepared formalin-fixed paraffin-embedded striatal tissues. In comparison with normal controls, MEnk-positive patches and pallidal MEnk-positive axon terminals were strongly present in patients with PD, showing characteristic distribution patterns. By comparison, in SND patients, there was striking diminution of MEnk staining in the putamen and ventrolateral portion of the GPe, while MEnk patches were persistent in the caudate nucleus.     

Low frontal glucose utilization in chronic schizophrenia: a replication study

Frontal/posterior ratios of cerebral glucose metabolism as determined by positron emission tomography were significantly lower in 13 chronic schizophrenic patients than in eight normal control subjects, as were absolute metabolic rates in both the frontal and posterior regions. The differences were not accounted for by cerebral atrophy.     

Akinesia and the frontal lobe.

A report of severe akinetic episodes in patients with Parkinson disease (PD) has been the stimulus for the following discussion of akinesia and its variants. Severe persistent akinesia may occur in frontal lobe impairment. Therefore, it is likely that extension of the Parkinsonian dysfunction into the frontal lobe causes severe akinesia which should be separated from the very common Parkinsonian hypokinesia. Another very common clinical phenomenon of PD is sudden freezing. Hence the frontal lobe--hardly regarded as a region of special interest in the realm of PD--can be the cause of severe and dangerous complications of PD. The term "arrest reaction" or "motor arrest" denotes a similar freezing. It is recommended to restrict these terms to certain forms of frontal lobe epilepsy. This discussion of hypokinetic and akinetic states should also include catatonia: a form of schizophrenia with a special type of akinesia. Though without major neuropathological substratum, this condition can, in extremely rare cases, lead to severe hyperthermia and fatal outcome (presumably via hypothalamic dysfunction).     

Elevated glucose utilization in subfornical organ and pituitary neural lobe of the Brattleboro rat

Homozygous Brattleboro rats have a genetic inability to synthesize vasopressin and therefore manifest the signs and symptoms of diabetes insipidus. Measurement of local cerebral glucose utilization in these rats has revealed increases specifically localized to the subfornical organ and pituitary neural lobe. Vasopressin replacement reverses the increased glucose utilization only in the subfornical organ. The results suggest that vasopressin regulates the rate of glucose metabolism in the subfornical organ.     

Increased iron content in the putamen of patients with striatonigral degeneration

Summary We measured the total content of iron, cooper, zinc and manganese in the putamen of four patients with striatonigral degeneration (SND) and age-and gender-matched normal controls. The iron content in the SND patients was five times greater than in the controls. Electron microscopic histochemistry revealed the iron reaction products in the pigments showing a triphasic pattern of coarse, electron-dense globules, fine granular and fibrillary materials, and lamellated structures. These findings suggest that increased iron deposition may be related to pigment formation in the putament of SND.