A five-year longitudinal study of the regional cerebral metabolic changes of a schizophrenic patient from the first episode using Tc-99m HMPAO SPECT

This is a naturalistic study of the relationship between cerebral metabolic activity, clinical symptoms and treatment response in a schizophrenic patient for 5 years from the onset of her illness. Serial technetium-99m-HMPAO brain SPECT was used to measure regional cerebral metabolism. The Cambridge Neurological Inventory and neuropsychological tests (WAIS-R verbal subscales, Wisconsin Card Sorting Test, semantic verbal fluency, logical memory in Weschler Memory Scale) were used for neurocognitive assessment. Under-activity of the left temporal area was observed in the course of patient illness despite remission of the psychotic symptoms. Bilateral prefrontal metabolic under-activity was noted at the emergence of negative symptoms, executive neurocognitive dysfunction and the treatment-resistant state. After response to clozapine, the right prefrontal activity returned to a normal level. Our findings suggested that persistent left temporal under-activity detected by SPECT despite clinical remission may indicate a vulnerability for further relapses and development of a treatment-resistant state. Treatment-resistant state, negative symptoms and executive neurocognitive deficit may involve abnormal prefrontal metabolic activity and can be alleviated in clozapine-responsive patients. Received: 10 August 1998 / Accepted: 7 December 1999     

A high-resolution single photon emission computed tomography study of verbal recognition memory in Alzheimer's disease

BACKGROUND: In view of the recent technological advances and its ease of availability, we used single photon emission computed tomography (SPECT) to examine the performance of early Alzheimer's disease (AD) subjects on a verbal recognition memory task. METHODS: Eighteen early AD and 10 matched healthy control subjects underwent split-dose (99m)Tc-HMPAO (Ceretec) SPECT using a verbal recognition memory and control task. SPECT images co-registered with MRI scans were used to determine relative regional cerebral blood flow (rCBF) changes in regions of interest. RESULTS: In healthy control subjects, verbal recognition increased rCBF in the right occipital region, thalamus, left prefrontal pole, posterior parietal region and cerebellum, and decreased rCBF in the right hippocampus. AD subjects showed bilateral prefrontal, posterior parietal and occipital increases, unilateral increase in the left posterior temporal region, and bilateral reductions in the hippocampus. Although activation was significantly different between the two groups in the right thalamus and left medial prefrontal region, the verbal recognition task did not enhance discrimination between groups. CONCLUSIONS: Compared with controls, AD subjects activate a similar but more extensive bilateral network during verbal recognition, possibly reflecting an attempt to compensate for impaired processing.     

Neuropsychological and structural brain lesions in multiple sclerosis: a regional analysis.

Quantified lesion scores derived from MRI correlate significantly with neuropsychological testing in patients with multiple sclerosis (MS). Variables used to reflect disease severity include total lesion area (TLA), ventricular-brain ratio, and size of the corpus callosum. We used these general measures of cerebral lesion involvement as well as specific ratings of lesion involvement by frontal, temporal, and parieto-occipital regions to quantify the topographic distribution of lesions and consequent effects upon cognitive function. Lesions were heavily distributed in the parieto-occipital regions bilaterally. Neuropsychological tests were highly related to all generalized measures of cerebral involvement, with TLA being the best predictor of neuropsychological deficit. Mean TLA for the cognitively impaired group was 28.30 cm2 versus 7.41 cm2 for the cognitively intact group (p less than 0.0001). Multiple regression analyses revealed that left frontal lobe involvement best predicted impaired abstract problem solving, memory, and word fluency. Left parieto-occipital lesion involvement best predicted deficits in verbal learning and complex visual-integrative skills. Analysis of regional cerebral lesion load may assist in understanding the particular pattern and course of cognitive deficits in MS.     

A case of Kleine-Levin syndrome examined with SPECT and neuropsychological testing

A case of Kleine-Levin syndrome with typical periodic hypersomnia and bulimia was diagnosed. On examination with single photo emission tomography (SPECT) (CERETEC) during a relapse period and 2 weeks later there was marked cortical hypoperfusion of the frontal and temporal lobes, especially on the left side as well as in the right parietal lobe. Neuropsychological testing performed 1 week after a relapse showed a reduction in encoding to memory function of verbal learning indicating neocortical damage of the left fronto-temporal region. A follow-up 2 months later after the patient had spontaneously recovered showed only a slight left fronto-temporal disturbance. CT and MRI of the brain were normal although the MRI showed a large and asymmetric mamillary body. Neuropsychological testing 6 years after recovery showed pronounced reduction in short-time verbal and visual memory. Seven years after recovery SPECT demonstrated a normalized frontal perfusion but still a slight hypoperfusion in the left temporal lobe. Our results correlate to autopsy findings in two cases described previously.     

Memory and language impairments and their relationships to hippocampal and perirhinal cortex damage in patients with medial temporal lobe epilepsy

Chronic medial temporal lobe epilepsy (MTLE) is associated with memory loss due to damage in the hippocampal system. To investigate the relationship between volume of medial temporal lobe structures and performance on neuropsychological tests, we studied 39 consecutive patients with MTLE and unilateral hippocampal atrophy (HA) determined by volumetric magnetic resonance imaging (MRI). Structures of interest comprised hippocampus, amygdala, and entorhinal, perirhinal, parahippocampal, and temporopolar cortices. The findings indicated that (1) performance was significantly worse in the group with left HA as compared with the group with right HA on general memory, verbal memory, delayed recall, and verbal fluency tests and the Boston Naming Test (BNT), and (2) the volume of the left hippocampus and also the degree of asymmetry of perirhinal cortex volume were significant and independent predictors of performance on general memory, verbal memory, and verbal fluency tests and the BNT in patients with MTLE.     

SPECT regional cerebral blood flow and neuropsychological testing in non-demented HIV-positive drug abusers: preliminary results

1. Non-demented HIV seropositive and seronegative methadone maintained patients and healthy volunteers (n = 10 each) participated. 2. All subjects underwent SPECT regional cerebral blood flow scanning following injection of Tc-99m HMPAO. All patients underwent neuropsychologic (NP) testing. 3. The left striatum/whole brain blood flow ratio was elevated in the HIV positive group compared to the healthy subjects. Two HIV positive patients had clearly abnormal striatal ratios. Both groups were impaired on NP testing; HIV+ patients were somewhat more impaired on tests of sustained attention and verbal memory. 4. SPECT scanning with Tc-99 HMPAO may identify a subgroup of HIV positive patients with evidence of CNS involvement prior to onset of dementia symptoms.     

A case of primary progressive multiple sclerosis with onset of memory impairment]

We report a 52-year-old woman with primary progressive multiple sclerosis (PPMS) presenting with chronic progressive memory impairment. From a couple of years prior to admission, she had developed impairment of her short-term memory. For example, she forgot her nephew's name, and spoke the same phrases again and again. She also sometimes forgot to turn off her gas stove and forgot things she bought in shops. Moreover, her mental activity gradually decreased and she became apathetic. However, she did not note her memory impairment, and had no hallucinations. She was admitted to our hospital on 20 May, 2003 because donepezil had been ineffective for treating her memory impairment. Neurologically, she showed bilateral horizontal gaze nystagmus, mild limb ataxia on the left and mildly ataxic gait. Neuropsychological examinations showed mildly impaired cognitive function, e.g., MMSE 25/30, WAIS-R full IQ 69 and especially in verbal short memory, which may represent temporal lobe dysfunction. Moreover, Benton's visual memory test revealed marked visual short-term memory impairment, while impaired performance on a Kana picking up test suggested mild to moderate attention impairment, which could have represented frontal lobe dysfunction. Brain MRI showed multiple T2-high plaque lesions close to the bilateral lateral ventricles, and bilateral optic nerve lesions enhanced by gadolinium. Also, spinal cord MRI showed a gadolinium enhanced lesion at Th5 on the left. Cerebral spinal fluid (CSF) examination showed normal cell count and protein level, and undetectable oligoclonal bands (OCB), but an elevated IgG index (1.1, normal < 0.85). Visual evoked potentials (VEPs) showed prolonged P100 latency bilaterally, indicating subclinical optic nerve lesions. She was thus diagnosed as having PPMS according to McDonald's diagnostic criteria for MS. 99mTc Single photon emission computed tomography (SPECT) showed a decreased cerebral blood flow (CBF) in the bilateral frontal and temporal lobes, which was consistent with her clinical features. PPMS patients generally present with chronic progressive spastic paraparesis and/or cerebellar ataxia. Cognitive impairments observed in PPMS are generally thought to be due to white matter lesions, i.e., subcortical dementia. However, some recent reports have shown MS patients with short-term memory impairment (antegrade amnesia) similar to cortical dementias such as Alzheimer's disease (AD). In such MS cases, visual short-term memory impairment seems characteristic of their cognitive impairment compared to AD cases. As well, the present case showed visual memory impairment as evaluated by Benton's memory test. Parietal and frontal lobes are reported to be important for verbal and visual working memory, respectively. Thus, in the present case, decreased CBF in the frontal and temporal lobes, which could have been due to a disconnection between cortices and subcortices caused by the white matter lesions, is consistent with the type of her cognitive dysfunction, i.e., notable visual memory impairment. PPMS may thus be an important disease as a differential diagnosis for chronic progressive dementia. Further neuropsychological and functional imaging studies will be necessary to achieve a better understanding of the mechanisms of cognitive impairment in PPMS.     

Semantic memory and frontal executive function during transient global amnesia.

To assess semantic memory and frontal executive function, two patients underwent neuropsychological testing during transient global amnesia (TGA) and after an interval of 6-8 weeks. In spite of a profound deficit in anterograde verbal and non-verbal memory, semantic memory was normal, as judged by category fluency measures, picture naming, and picture-word and picture-picture matching, and reading ability was normal. Similarly, there were no deficits on a number of tests known to be sensitive to frontal executive dysfunction. A hexamethylpropyleneamine-oxime (HMPAO) single photon emission CT (SPECT) scan, obtained on one patient 24 hours post-TGA, showed focal left temporal lobe hypoperfusion which had resolved three months later. The observed dissociation between episodic and semantic memory is discussed in the light of contemporary cognitive theories of memory organisation.     

Memory during subclinical hippocampal seizures

We performed neuropsychological testing in 2 patients during subclinical hippocampal seizures recorded with depth electrodes. Neither subject showed impairment of consciousness, orientation, motor skills, or verbal fluency. The rapidity of recall of a well-learned word list was impaired in 1 subject during ictal fast spiking in the left hippocampus. Subclinical seizure activity may be responsible for a portion of the memory deficits found in patients with epilepsy.     

On the nature of memory disturbance in multiple sclerosis

Abstract

Thirty-seven patients with multiple sclerosis (MS) were compared to 26 normal controls of equivalent age, education, and verbal intelligence on measures of verbal learning and memory (Digit Span and Supraspan, Brown-Peterson Distractor Task, Selective Reminding Test, Story Recall, and Free Verbal Recall) and verbal fluency (Letter and Animal Fluency). The MS patients exhibited deficits on measures of secondary (long-term) memory and verbal fluency, but performed normally on measures of primary (short-term) memory, recognition memory, and rate of forgetting from secondary memory. These results suggest that the memory disturbance in MS results primarily from an impaired ability to access information from secondary memory, while encoding and storage capacity is intact. Degree of memory impairment was unrelated to length of illness, severity of disability, or self-reported depression.     

Intracarotid Amobarbital Procedure as a Predictor of Material-Specific Memory Change After Anterior Temporal Lobectomy

Summary: Memory testing during the intracarotid amobarbital procedure (IAP) is used extensively to identify temporal lobe surgery candidates "at risk" for developing severe postoperative anterograde amnesia. However, the utility of the IAP in predicting commonly observed material-specific memory deficits has not been thoroughly investigated. We examined the utility of contralateral IAP memory testing, as an index of the functional capacity of the surgical temporal lobe, to predict postoperative material-specific memory changes on the Wechsler Memory Scale-Revised (WMS-R) in patients with left hemisphere speech dominance undergoing left (n = 32) and right (n = 31) temporal lobectomy (TL). Left TL patients who "passed" contralateral IAP memory testing (368% recognition of memory items) had significantly greater verbal memory decrements than those who "failed" the IAP, presumably as a result of removal of functional tissue. A similar relationship between contralateral IAP performance and visual memory performance was not observed among right TL patients. Thus, the functional adequacy of the tissue to be resected appears to be inversely related to postoperative verbal memory decrement, at least among left TL patients. This relationship is consistent with results of recent studies demonstrating an inverse relationship between verbal memory decrements after left TL and preoperative neuropsychological verbal memory performance, magnetic resonance imaging (MRI) hippocampal volumes, and degree of mesiotemporal sclerosis (MTS).     

Relation between medial temporal atrophy and functional brain activity during memory processing in Alzheimer's disease: a combined MRI and SPECT study

OBJECTIVE: To investigate the relation between atrophy of the hippocampal region and brain functional patterns during episodic memory processing in Alzheimer's disease. PATIENTS AND METHODS: Whole brain structural magnetic resonance imaging (MRI) data and single photon emission computed tomography (SPECT) measures of regional cerebral blood flow (rCBF) were obtained during a verbal recognition memory task in nine subjects with mild Alzheimer's disease and 10 elderly healthy controls. Using the statistical parametric mapping approach, voxel based comparisons were made on the MRI data to identify clusters of significantly reduced grey matter concentrations in the hippocampal region in the Alzheimer patients relative to the controls. The mean grey matter density in the voxel cluster of greatest hippocampal atrophy was extracted for each Alzheimer subject. This measure was used to investigate, on a voxel by voxel basis, the presence of significant correlations between the degree of hippocampal atrophy and the rCBF SPECT measures obtained during the memory task. RESULTS: Direct correlations were detected between the hippocampal grey matter density and rCBF values in voxel clusters located bilaterally in the temporal neocortex, in the left medial temporal region, and in the left posterior cingulate cortex during the memory task in the Alzheimer's disease group (p < 0.001). Conversely, measures of hippocampal atrophy were negatively correlated with rCBF values in voxel clusters located in the frontal lobes, involving the right and left inferior frontal gyri and the insula (p < 0.001). CONCLUSIONS: Hippocampal atrophic changes in Alzheimer's disease are associated with reduced functional activity in limbic and associative temporal regions during episodic memory processing, but with increased activity in frontal areas, possibly on a compensatory basis.     

Verbal learning and forgetting in patients with temporal lobe epilepsy

Studies comparing non-surgical patients with left or right temporal lobe epilepsy (TLE) have shown irregular differences in verbal learning and memory. We assessed the performance of unoperated patients with epileptogenic temporal lobe lesions or cryptogenic TLE using a selective reminding procedure for the learning of a word list, and five delayed trials for the recall of learned words. On the selective reminding procedure, patients with left TLE were found to be more impaired than those with right TLE and controls, in agreement with the role of the left temporal lobe in verbal learning. The patients with right TLE were more impaired than the controls, possibly due to the semantic organization of the word list The rate of forgetting learned words was similar in the patient and control groups, suggesting that patients with left TLE can normally retain and/or retrieve stored items. These data support the hypothesis that distinct functional systems subserve learning and memory. Comparisons of the patient subgroups with epileptogenic lesions (hippocampal sclerosis or low-grade glioma) and those with cryptogenic TLE did not reveal any significant difference in learning or in memory, suggesting that epileptiform activity could affect verbal performance as a detectable temporal lesion.     

Cognitive Consequences of Two-Thirds Anterior Temporal Lobectomy on Verbal Memory in 144 Patients: A Three-Month Follow-Up Study

Previous studies have shown that left temporal lobectomy for intractable epilepsy can lead to verbal memory deficits. However, patients with left temporal lobe epilepsy (LTLE) frequently have impaired verbal memory preoperativel. The present analysis of 144 patients who underwent temporal lobe resections for either left (n = 68) or right (n = 76) temporal lobe epilepsy (LTLE, RTLE) addressed the questions of (a) whether a left two-thirds anterior temporal lobectomy (ATL) increases deficits in these qualitative aspects of verbal memory already impaired preoperatively, and (b) whether other aspects of verbal memory are additionally affected. We also evaluated possible determinants of preoperative abilities and postoperative changes, using multiple regression analysis. Preoperatively, patients with LTLE differed from patients with RTLE only in poorer performance on measures of long-term consolidation/retrieval (delayed recall). This was related to hippocampal pathology and seizure severity. Only left temporal lobe resections resulted in significant deterioration in verbal learning and memory. Acquisition over learning trials and recognition deteriorated most markedly, whereas performance in long-term consolidation/retrieval showed only minor changes. Preoperative performance levels, chronological age, the extent of the en bloc resection, preoperative performance on figural memory, and preoperative seizure severity were valuable determinants of postoperative changes in acquisition and recognition. In contrast, changes in consolidation/retrieval related only to preoperative ability. Left two-thirds ATL leads to new impairment in addition to preexisting memory deficits. The finding that left temporal lobectomy affects verbal acquisition and recognition more than long-term consolidatiodretrieval, including the different determinants of these changes, most likely reflects the differential effects of surgery on mesial temporal and neocortical temporal functions.     

Relationship between regional cerebral blood flow and verbal fluency in Alzheimer's disease

Category and letter verbal fluency tests are widely used for dementia detection and severity measure. Performances of these tasks have been regarded to be mainly associated with the left frontal lobe function. However, some recent studies suggest that there are different neuropsychological bases between these two tasks, and the brain region which contributes to these performances still remains unclear in Alzheimer's disease (AD). To clarify the neural basis of verbal fluency in AD, we examined the relationship between performances of these tasks and regional cerebral blood flow (rCBF). Twenty-five AD patients were administered verbal fluency tasks and single photon emission computed tomography (SPECT) scans. Thirteen cortical regions of interest were symmetrically defined in each hemisphere. Letter fluency scores were correlated significantly only with the left prefrontal (Brodmann's area (BA) 10-46) regional cerebral blood flow (rCBF). In contrast, category fluency scores were correlated most strongly with the left temporal rCBF and also with the left prefrontal (BA 10-46) rCBF. In conclusion, the present study suggests that left prefrontal (BA 10-46) dysfunction contributes to decline in both letter and category fluency scores in AD, while typical posterior dysfunction of AD has a closer relationship with decline in category fluency scores.     

语义性痴呆的临床、认知和影像学特征研究-附3例报告

目的 分析语义性痴呆(semantic dementia，SD)患者的临床、认知缺损与保持模式和影像学特征。方法 针对3例SD患者完成详细的病史采集、一系列神经心理测验和头颅核磁共振(MR)检查。结果 SD的临床特点是起病年龄相对较轻、以命名障碍为最早最严重的症状、应用乙酰胆碱酯酶抑制剂治疗有较明显的不良反应。SD的认知特点是呈现语义记忆的选择性损害、物品命名、列举某一范畴的例子、词语的阅读理解和语义相似性判断等项目严重受损；情景记忆、空间知觉、执行功能和非言语的解决问题能力相对正常。SD的影像学特点是在冠状位MR摄片上呈现左颞叶新皮层局限性严重萎缩。结论 SD患者具有独特的临床、认知和影像学特征。     

Bilateral hemispheric alteration of memory processes in right medial temporal lobe epilepsy

OBJECTIVE: Functional MRI (fMRI ) was used to investigate right medial temporal lobe epilepsy (RTLE) effects on verbal memory. METHODS: BOLD fMRI data were collected from seven right sided MTLE patients (RTLE) and compared with the data previously acquired from seven left sided MTLE patients (LTLE) and 10 control subjects. Twenty two contiguous images covering the whole brain were acquired using an EPI echoplanar sequence. Subjects were instructed to learn a list of 17 words, and to recall it immediately and at 24 hours interval. Group analyses were performed using SPM96. RESULTS: RTLE patients retrieval performances were significantly impaired as compared with the performance of control subjects. As compared with control subjects and LTLE patients, RTLE patients exhibited a different pattern of hemispheric activations and a global decrease in left hemisphere functional activity. CONCLUSION: MTLE cannot be considered as a model of pure well lateralised hippocampal dysfunction. The verbal memory impairment depicted in RTLE patients may be considered as the witness of a bilateral impairment of the neuroanatomical circuits subserving memory.     

Neuronal substrates for semantic memory: a positron emission tomography study in Alzheimer's disease

We examined 57 patients with mild Alzheimer's disease by using three kinds of verbal semantic memory tests (category fluency, confrontation naming and generation of verbal definition) and correlated each score with regional cerebral glucose metabolism determined by (18)F-fluorodeoxyglucose and positron emission tomography. The scores of all three verbal semantic memory tests correlated significantly with regional cerebral glucose metabolism in the left inferior temporal gyrus, even after controlling for the effects of age, sex and educational attainment. In contrast, the scores of the word recall test did not correlate significantly with regional cerebral glucose metaboliosm in the left inferior temporal gyrus, neither before nor after controlling for these confounders. Our results suggested that the left inferior temporal lobe contributes to verbal semantic memory.     

Verbal fluency and positron emission tomographic mapping of regional cerebral glucose metabolism.

Impairment in verbal fluency (VF) has been a consistently reported clinical feature of focal cerebral deficits in frontal and temporal regions. More recent behavioral activation studies with healthy control subjects using positron emission tomography (PET), however, have noted a negative correlation between performance on verbal fluency tasks and regional cortical activity. To see if this negative relationship extends to steady-state non-activation PET measures, thirty-three healthy adults were given a VF task within a day of their 18F-2-fluoro-2-deoxy-D-glucose PET scan. VF was found to correlate positively with left temporal cortical region metabolic activity but to correlate negatively with right and left frontal activity. VF was not correlated significantly with right temporal cortical metabolic activity. Some previous studies with normals using behavioral activation paradigms and PET have reported negative correlations between metabolic activity and cognitive performance similar to that reported here. An explanation for the disparate relationships that were observed between frontal and temporal brain areas and VF might be found in the mediation of different task demands by these separate locations, i.e., task planning and/or initiation by frontal regions and verbal memory by the left temporal area.     

Relation of cortical language distribution and cognitive function in surgical epilepsy patients

PURPOSE: To investigate the relation between the number and spatial distribution of language sites and specific patient-and epilepsy-related variables. METHODS: Patients with stimulation-induced reading or naming errors from anterior or inferior temporal cortex (i.e., atypical temporal language sites) were compared with those with language sites confined to Wernicke's area (WA) in the posterosuperior temporal and inferior parietal perisylvian area. In a consecutive series of 44 left hemisphere language dominant patients with complex partial seizures before left temporal lobectomy, correlations were compared between cortical language distribution and measures of cognitive function. RESULTS: Patients with atypical temporal language sites (group 1) had significantly fewer years of education that did patients with language sites in WA (group 2). Patients in group 1 had poorer verbal learning and fluency than did patients in group 2. Patients with IQ <80 were significantly more likely to have multiple sites where stimulation disrupted language than did patients with normal IQ. Number of language sites had significant negative correlations with full-scale IQ, and measures of confrontation naming, verbal fluency, and immediate verbal memory. CONCLUSIONS: Language cortex has a wider spatial distribution in epilepsy surgery patients with lower intelligence, poorer education, and worse verbal and memory skills.