Microstructural integrity of cerebral fiber tracts in hereditary spastic paraparesis with SPG11 mutation.

BACKGROUND AND PURPOSE: ARHSP-TCC is characterized by progressive leg spasticity, ataxia, and cognitive dysfunction. Although mutations in the human SPG11 gene were identified as responsible for ARHSP-TCC, the cerebral fiber integrity has not been assessed systemically. The objective of this study was to assess cerebral fiber integrity and its clinical significance in patients with ARHSP-TCC. MATERIALS AND METHODS: Five patients from 2 families who were clinically and genetically confirmed to have ARHSP-TCC were examined by neuropsychological evaluation and DSI of the brain. We performed voxel-based GFA analysis for global white matter evaluation, tractography-based analysis for tract-to-tract comparisons, and tract-specific analysis of the CST to evaluate microstructural integrity along the axonal direction. RESULTS: The neuropsychological evaluation revealed widespread cognitive decline across all domains. Voxel-based analysis showed global reduction of GFA in the cerebral white matter. Tractography-based analysis revealed a significant reduction of the microstructural integrity in all neural fiber types, while commissure and association fibers had more GFA reduction than projection fibers (P < .00001). Prefrontal and motor portions of the CC were most severely affected among all fiber tracts (P < .00001, P = .018). Tract-specific analysis of the CST validated a "dying-back" phenomenon (R(2) = 0.68, P < .00001). CONCLUSIONS: There was a characteristic gradation in the reduction of microstructural integrity among fiber types and within the CC in patients with the SPG11 mutation. The dying-back process in CST might explain the pathogenic mechanisms for ARHSP-TCC.

New assay for old markers-plasma beta amyloid of mild cognitive impairment and Alzheimer's disease.

Although there is a consensus on the reduced levels of Aß1-42 in the CSF of patients with AD, studies of plasma Aß levels were inconsistent and have limited clinical value. We developed an immunomagnetic reduction assay (IMR) to determine the plasma levels of Aß. We surveyed patients with varying AD severity (CDR = 0.5, n=16; CDR ≥ 1, n=18) and controls (n=26). Significant group differences were apparent in the levels of Aß1-42 (F = 5.54, p = 0.002) and the Aß1-42/Aß1-40 ratio (F = 24.198, p < 0.001). Post-hoc analyses showed significant differences in the Aß1-42 levels of controls and AD patients (p = 0.001) and in the Aß1-42/Aß1-40 ratio of control, MCI and AD subjects (all p ≤ 0.001). Regression analysis of Aß1-42/Aß1-40 ratios on dementia severity showed an adjusted R2 of 0.553 (p = 0.001). We identified a cut-off of 16.1 pg/ml for Aß1-42 to differentiate control subjects from patients (both AD and MCI) with 85.3% sensitivity and 88.5% specificity. We also obtained a cut-off value of 0.303 for Aß1-42/Aß1-40 ratios with 85.3% sensitivity and 96.2% specificity. APOE 4 carriers had significantly higher Aß1-42/Aß1-40 ratios than the non-carriers (F = 4.839, p = 0.015). An independent group of case-control subjects validated both cut-off values for Aß1-42/Aß1-40 (100% sensitivity and 83.3% specificity) and for Aß1-42 (100% sensitivity and 75.3% specificity). In a subgroup of longitudinal follow- up study, we found that the plasma Aß was relatively stable with an interval of approximately 3 months. In conclusion, we found that the plasma Aß1-42 is a useful biomarker for AD. The Aß1-42/Aß1-40 ratio improves the diagnostic power of the plasma Aß biomarkers. The iron nanoparticles and IMR provides a novel method to measure plasma Aß and could serve as an important clinical tool for the diagnosis of neurodegenerative diseases.

Chinese writing function in patients with left versus right putaminal hemorrhage.

This study was designed to explore the Chinese writing function of patients with subcortical stroke. Two cohorts of patient subjects with either the left or the right subcortical strokes, mainly putaminal hemorrhagic strokes, and one group of normal controls participated in the study. All participants received a writing test battery including the three aspects of writing function, that is, Spontaneous Writing, Writing to Dictation, and Writing from Copy, as well as a battery of non-writing linguistic tests. Comparing with normal controls revealed that writing function change occurred in both patient groups. The deficits in the patients with the left subcortical stroke essentially included Spontaneous Writing, and Writing to Dictation. These impairments were most likely secondary to aphasic disorders. The writing problem, mainly Writing from Copy, was noted in the patients with the right subcortical stroke. This deficit, however, was independent of the core linguistic impairment. On the basis of the results, we suggest that the lesion involving white matter in the left hemisphere probably interrupts left perisylvian cortical language organization in a manner that produces problems with spontaneous writing and writing to dictation, which are language-related, associated with lesion in the dominant hemisphere. This further suggests that left or right subcortical lesions in the putamen and surrounding white matter are associated with differential effects (language vs. non-language based effects) which are similar to such differences observed with left vs. right cortical lesions.

Olfactory function in patients with nasopharyngeal carcinoma following radiotherapy.

The aim of this study was to examine the impact of radiation treatment on olfactory function in patients with nasopharyngeal carcinoma (NPC). An olfactory function test battery was administered to 25 adult NPC patients having received radiotherapy, 24 adult nasopharyngeal carcinoma patients awaiting to receive radiation treatment, and 36 adult normal control subjects. Members of the three groups were matched in terms of age, educational level, and full-scaled IQ score. Comparing the test results revealed that the NPC patients with radiotherapy had olfactory information processing impairments including absolute threshold, odour-tactile cross-modality matching, verbal identification of odours, and recall and recognition of identity of odours. The deficits of suprathreshold olfactory functioning in these patients did not seem to arise from impaired absolute threshold sensitivity. Provided that the results are reproducible, an evaluation of olfactory functioning in NPC patients during the period of radiotherapy may be useful for detecting or even avoiding side effects of radiation.

Neuropsychological function in patients with nasopharyngeal carcinoma after radiotherapy.

A neuropsychological test battery was administered to 27 adult patients with nasopharyngeal carcinoma (NPC) who had received radiotherapy, 28 adult patients with NPC awaiting radiotherapy, and 35 normal adult controls. The 27 patients with radiotherapy had a conventional dosage, 220 cGy per fraction, or less. The median interval between the completion of radiotherapy and the evaluation of neuropsychological function was 1.7 years. Groups were matched for age and educational level. The results showed that our NPC group with radiotherapy had neuropsychological impairments in the areas of auditory attention/concentration, immediate and delayed verbal recall and immediate visual recall, and recent memory, higher-order visuospatial abilities, and bimanual dexterity. Thus neuropsychological dysfunction may occur in patients with NPC within the first 2 years after radiotherapy.

Factor structure and age effects with an aphasia test battery in normal Taiwanese adults.

This study was designed to explore in a Taiwanese sample the factor structure of an aphasia test battery composed of parts of several standardized aphasia tests. A secondary goal was to assess effects of normal aging on the obtained factors. The sample was 120 healthy Taiwanese adults, ranging in age from 30 to 78 years. Principal-components analysis of the aphasia test battery revealed 5 factors: verbal comprehension, effortful writing, word production, automatized writing, and visuomotor coordination skills. Because the latter 2 factors have common psychological features, they can be combined and reinterpreted as a factor on the mechanics of writing. Further data analysis with factor scores shows that aging unfavorably influences verbal comprehension, effortful writing processing, and word production functions.

Prolonged circulatory arrest in moderate hypothermia with retrograde cerebral perfusion. Is brain ischemic?

BACKGROUND: Circulatory arrest (CA), which provides a bloodless field and good visualization without the need of aortic cross-clamp, is commonly used to facilitate repair of aortic lesions. However, extended periods of CA may impair cerebral metabolism and cause ischemic injury. Studies were performed to evaluate the efficacy of retrograde cerebral perfusion (RCP) in protecting the brain from ischemic injury during a prolonged period of CA in moderate hypothermia. METHODS AND RESULTS: Twenty-three patients (18 men and 5 women) were operated on for aortic lesions (17 acute type A aortic dissection and 6 chronic type A aortic dissection with Marfan's syndrome). The aortic operations were performed with CA (58 to 104 minutes; mean +/- SD, 75 +/- 12 minutes) at a rectal temperature of 23.3 +/- 0.5 degrees C (21 degrees C to 25 degrees C). For RCP, cold (14 degrees C to 18 degrees C) oxygenated blood (300 mL/min) was pumped to the superior vena cava with internal jugular venous pressure of 15 +/- 5 mm Hg. The cardiopulmonary bypass time was 157 +/- 18 minutes. Cortical blood flow during RCP detected by subdural laser Doppler probe was 10 +/- 5% of baseline. Percent oxygen extraction and pyruvate and lactate levels (26 +/- 2% and 0.43 +/- 0.17 and 45 +/- 16 mg/dI) were insignificantly different from those before CA (28 +/- 3% and 0.71 +/- 0.08 and 62 +/- 20 mg/dL, P > .05). Creatine kinase-BB isoenzyme was undetectable. All but 1 patient survived the operation (95.5%) and woke up without neurological deficit. Follow-up (mean, 13 months) was complete in all survivors. There were no late deaths. Cerebral functional studies performed 3 months after discharge showed results insignificantly different from those of the normal control subjects. CONCLUSIONS: There is no evidence of ischemia of the brain during prolonged moderate hypothermic CA with the aid of RCP. Retrograde cerebral perfusion effectively extends the safe time of CA. Deep hypothermia during CA seems unnecessary.

Chronic elemental mercury intoxication: neuropsychological follow-up case study.

In initial and follow-up investigations of neuropsychological function in a patient with elemental mercury intoxication, his scores were compared with those of a group of normal control subjects matched for sex, age and education. Each subject received a comprehensive neuropsychological examination including a personality inventory. On the initial examination the results indicated that the patient had a significant depression of performance intellectual functioning, impairments of attention, non-verbal short-term memory and visual judgement of angles and directions, psychomotor retardation and personality changes including depression, anxiety, desire to be alone, lack of interest and sensitivity to physical problems. Such an impairment picture is compatible with the previous observations of individuals with chronic exposure to elemental, organic or inorganic mercury. The follow-up study was undertaken about 1.5 years later. The results show that the patient's cognitive and personality functions were fully recovered. Our findings thus suggest a reversibility of impaired neuropsychological function in persons with elemental mercury poisoning if a prompt removal from the toxic environment is accomplished, together with proper medical treatment.

Cognitive dysfunction in early onset parkinsonism.

Cognitive functions of 24 patients with early onset parkinsonism (age of onset before 40 years) and 24 controls were investigated by a battery of neuropsychological tests. Patients were shown to be impaired in performance IQ (PIQ), conceptual ability and regulation behavior, memory, visuospatial perception, and manual dexterity. Patients were also shown to have a higher Zung Depression score. However, analysis of the testing scores appeared to indicate that only a small portion of poor performance on neuropsychological tests are depression related. The results demonstrated that patients with early onset parkinsonism, in whom the factor of aging is not as important, still show cognitive dysfunction and suggested that Parkinson's disease itself can cause cognitive impairment.

Neuropsychological deficits in a case of H2S anoxic encephalopathy.

A comprehensive examination of the neuropsychological status of a young male patient of anoxic encephalopathy due to acute hydrogen sulfide intoxication was made. Agraphia, acalculia, deficits of associative verbal fluency and design fluency, and general intellectual deterioration were noted. Qualitative analysis of number operation revealed a specific impairment in the performance of division. Further analysis of graphic output showed a phonological substitution feature. The disorder of written language in the absence of disorders of language and communication in other modalities and praxis can be considered pure agraphia. The possible neural substrate for pure agraphia and partial acalculia was also discussed.

Chronic occupational exposure to manganese and neurobehavioral function.

Comprehensive examinations of neurobehavioral function were performed in two groups of workers with chronic exposure to industrial manganese, and two control groups. Group 1 included 17 exposed workers without parkinsonism while Group 2 consisted of four exposed workers with parkinsonian syndrome resulting from chronic manganese poisoning. Group 3 was composed of eight idiopathic parkinsonian patients while Group 4 included 19 control subjects. Age, sex, and educational level of these four groups were matched. The neuropsychological battery consisted of tests of orientation, intelligence, learning and memory, language and communication, visuospatial and visual perception, visual attention, manual dexterity, and information processing speed. There was no evidence of neurobehavioral impairment in the non-parkinsonian workers whereas impaired general intelligence, visuoperceptive impairment and defective manual dexterity, as well as slowdown in response speed were manifested in the parkinsonian workers.

Patterns of lateral preference: an American-Chinese comparison.

Lateral preference patterns of Chinese and Anglo-Americans were assessed to examine the influence of gender and family history for each group. Ninety-two Chinese and a like number of Anglo-Americans were presented with a Chinese and English version of the Lateral Preference Schedule, respectively. Results indicated that Anglos were significantly less right oriented on measures of general handedness and strength. An interaction for the visually guided motor factor indicated that Anglo males were significantly more bilateral than females of their Chinese counterparts. When family history was investigated, it was found that Chinese parents were significantly more right lateralized than their Anglo cohorts. A step-wise discriminant analysis indicated that scores on both parents' lateral preference and the visually guided motor factor best predicted group membership. It was concluded that performance on the visually guided motor factor concomitant with familial lateral preference patterns best represented ethnic group differences.

Laterality effects in cued auditory asymmetries.

The effect of cued attention on perceptual asymmetries was investigated with normal adults who differed in their lateral preference. Specifically, 15 right lateralized and a like number of mixed/left subjects were isolated on the basis of their lateral preference for visual guided motor activities. Learners' attention was directed to the left, right and both channels of dichotically presented verbal stimuli. Instructions to shift attention had little effect on the usual right-ear advantage for subjects who displayed a right of midline preference pattern. More bilateral subjects significantly improved their recognition of stimuli presented to the directed ear.