Combined 99mTc-ECD SPECT and neuropsychological studies in MCI for the assessment of conversion to AD.

Identifying pre-clinical Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI) is a major issue in clinical diagnosis. Establishing a combination of predictive markers from different fields of research might help in increasing the diagnostic accuracy. Aim of this study was to evaluate the potential role of 99mTc-ECD single photon emission computed tomography (SPECT) and memory scores in predicting conversion to AD in MCI subjects. Thirty-one MCI subjects underwent a clinical and neuropsychological examination, and a regional cerebral blood flow (rCBF) SPECT scan at baseline. Subjects had been followed periodically through 2 years in order to monitor the progression of cognitive symptoms. Canonical variate analysis of principal components was able to separate all subjects who converted to AD from those who remained stable, the former being characterized by a specific hypometabolic pattern, involving the parietal and temporal lobes, precuneus, and posterior cingulate cortex. Canonical correlation analysis of combined baseline memory deficits and rCBF SPECT images identified pre-clinical AD with a sensitivity and specificity of 77.8%. The pattern of hypoperfusion 99mTc-ECD SPECT and the severity of memory deficits predict the risk of progression to probable AD dementia in MCI subjects.

Weather conditions and transient global amnesia. A six-year study.

OBJECTIVES: The aetiology of transient global amnesia (TGA) is still unknown. Various events or activities have been shown to trigger TGA. A common feature of these events is an increased sympathetic activity which in turn may be influenced by meteorological factors. This prompted us to evaluate the influence of climatic parameters, and their variation on the incidence of TGA. METHODS: A total of 223 cases of TGA admitted to our hospital over a six-year period were studied. The study consisted of a comparison between the climatic parameters of days with TGA and those without TGA. The meteorological database included daily values of parameters recorded at the meteorological station of the town during this period. RESULTS: The onset of TGA was significantly correlated with lower daily,monthly and seasonal temperature values. Most cases of TGA were found when the temperature was less than 6.9 degrees C,whereas the frequency of TGA was minimum when it was more than 24 degrees C (P < 0.0001). Only temperature had a significant independent effect: an increase of 1 sd = 8.4 degrees C decreases the TGA admission odds of 0.78 (95 % CI: 0.62 to 0.97), i.e -22% (95 % CI: -38% to -3 %). CONCLUSIONS: This study suggests an association between TGA occurrence and low ambient temperature. Multicentre studies taking into account climatic differences between countries are necessary to confirm our findings.

Influence of rehabilitation on language skills in aphasic patients. A controlled study.

The influence of language rehabilitation on specific language skills (speaking, understanding, writing, and reading) was investigated in 281 aphasic patients (162 reeducated and 119 controls) who were subjected to a second examination no less than six months after the first. The relationship of the following factors to improvement was studied: (a) time between onset of aphasia and first examination; (b) type of aphasia; (c) overall severity of aphasia on first examination; (d) presence or absence of rehabilitation between first and subsequent examination. It was found that rehabilitation has a significant positive effect on improvement in all language skills. Time between onset and first examination and overall severity of aphasia were negatively related to improvement. The relationship of type of asphasia to improvement was not significant. Additional evidence of the efficacy of rehabilitation is provided by experience with patients who began language therapy several months or years after the onset of their language disorder.

Right-left asymmetry in anterior speech region.

The extent of the anterior speech region (defined as pars opercularis and pars triangularis of the third frontal convolution) and of the planum temporale was measured in 12 brains belonging to strictly right-handed persons. When the portion of the anterior speech region visible on the hemispheric surface was measured, no interhemispheric difference was found. By contrast, when both the extrasulcal and intrasulcal portions of cortex were considered, the anterior speech region in the left hemisphere was found to be significantly larger than the homologous areas in the right hemisphere. The planum temporale was significantly larger on the left than on the right, but there was no necessary correspondence between the presence of a larger right planum and a larger right anterior speech region.

Gadolinium-pentetic acid magnetic resonance imaging in patients with relapsing remitting multiple sclerosis.

Ten patients with relapsing-remitting multiple sclerosis have been studied by serial gadolinium-pentetic acid magnetic resonance imaging (MRI) every 14 days for 3 months. At the end of the follow-up, seven relapses occurred in six patients; no therapy was administered during the study. Ninety-three enhancing lesions were collected in eight patients. With regard to the duration of the enhancement, 32 lesions were detected in only one MRI scan and 32 were found in more MRI scans (most of the lesions occurring in two serial examinations). Four old lesions increased their size with delayed enhancement. Correlation was found between the relapses and the gadolinium-pentetic acid-enhancing areas only for one brain-stem and two cervical spinal cord lesions. Gadolinium-pentetic acid MRI provides useful information about activity of the disease that cannot be obtained clinically even if the dynamic of the lesions may be undervalued in old plaques.

Differential level of platelet amyloid beta precursor protein isoforms: an early marker for Alzheimer disease.

OBJECTIVE: To determine whether a differential level of platelet amyloid beta precursor protein (APP) isoforms is specifically related to Alzheimer disease (AD) and whether it shows a correlation with the progression of clinical symptoms. DESIGN: After subjects were grouped according to diagnosis and severity of dementia, APP isoform levels in platelets were compared. SETTING: University medical centers. PATIENTS: Thirty-two patients who fulfilled diagnostic criteria for probable AD, 25 age-matched control subjects, and 16 patients with non-AD dementia. MAIN OUTCOME MEASURE: The levels of APP isoforms were evaluated by means of Western blot analysis and immunostaining of whole platelets. Messenger RNAs for APP transcripts were also evaluated by means of reverse transcriptase polymerase chain reaction. RESULTS: The ratio between the intensity of the 130-kd and 106- to 110-kd APP isoforms was significantly lower in the AD group (0.31 +/- 0.15, mean +/- SD) compared with both controls (0.84 +/- 0.2) and non-AD subjects (0.97 +/- 0.4). The ratio of platelet APP isoforms in patients with AD grouped by Clinical Diagnostic Rating score significantly correlated with the severity of the disease (Pearson correlation coefficient, followed by Bonferroni correction, P = .01). Reverse transcriptase polymerase chain reaction experiments showed that APP transcripts in all experimental groups were equally expressed. CONCLUSIONS: The pattern of platelet APP isoforms is specifically altered in patients with AD. In addition, the alteration of platelet APP isoforms shows a positive correlation with the progression of clinical symptoms, supporting the possibility to consider this peripheral parameter as a marker of progression of the disease. These alterations are not related to abnormalities of APP isoforms messenger RNAs in platelets.

Fatal familial insomnia in a new Italian kindred.

The authors report a new kindred with fatal familial insomnia (FFI)--an inherited prion disease. The propositus had behavioral, sleep, cognitive, and motor impairment associated with thalamic and olivary atrophy. Spongiosis was confined to the parahippocampal gyrus. Protease-resistant prion protein (PrP(res)) was present with widespread distribution. The propositus fits the histopathology of FFI with similar clinical duration and confirms the role of disease duration in determining histopathology and PrP(res) distribution in FFI.

Jargonagraphia: clinical and neuropsychological correlates.

Jargonagraphia (i.e., fluent, unintelligible writing with abundant paragraphias and preserved mechanics of writing) is considered to be an infrequent symptom of Wernicke's aphasia. Six cases fulfilling the definition of jargonagraphia were found in a retrospective series of 1076 consecutive aphasics and the neuropyschological and clinical correlates of this phenomenon were analysed. Jargonagraphia was not qualitatively uniform, and its appearance seems to be conditioned by the interaction of an increased "impulse to write" with disrupted language mechanisms.

Alexia in recent and late Broca's aphasia.

The hypothesis was tested that alexia associated with Broca's aphasia may often be a residual receptive disorder of a broader picture of global aphasia. It was found that alexia does tend to be associated, as expected, to the long-standing Broca's aphasias more often than to the recent ones. However, the CT scan failed to disclose larger and more posterior lesions in Broca's alexic than in Broca's non-alexic patients.

Absence of a correlation between T lymphocyte subsets and clinical activity in relapsing-remitting multiple sclerosis.

Cytofluorographic analysis of CD3+, Tac+, HLA-DR+ peripheral blood lymphocytes and CD4/CD8 ratio was performed monthly, over a 10-month period, in a group of 16 patients with multiple sclerosis (MS). No correlation was found between clinical relapses and fluctuations in the lymphocyte subsets, although patients who were in remission throughout the study showed a number of CD3+ cells and a CD4/CD8 ratio significantly lower than those in normal controls. We concluded that changes in peripheral blood lymphocyte subsets are not related to the disease process and their measurement is not helpful in monitoring the illness.

Neuropsychological assessment in multiple sclerosis: a follow-up study with magnetic resonance imaging.

Nineteen moderately impaired patients with clinically definite multiple sclerosis and an initially relapsing-remitting course were included in a neuropsychological and magnetic resonance imaging (MRI) follow-up study. The average test/re-test interval was about 2 years. The neuropsychological findings were indicative of a very mild overall impairment; the patients, as a group, showed no evidence of cognitive deterioration in the follow-up period. A numerical estimation of the severity of cerebral demyelination shown by MRI did not indicate a significant change. No correlation between cognitive performance variations and MRI changes was found.

Prevalence and pattern of cognitive impairment in systemic lupus erythematosus patients with and without overt neuropsychiatric manifestations.

The prevalence and pattern of cognitive impairment in systemic lupus erythematosus (SLE) patients with (NPSLE) and without (nSLE) overt neuropsychiatric manifestations were investigated. Fifty-two nSLE patients, 23 NPSLE patients and 27 healthy controls were evaluated with a battery of standardized neuropsychological and psychological tests. Disease duration, disease activity index, and current corticosteroid therapy were collected. Cognitive impairment was identified in 14 (26.9%) and in 12 (52.2%) of subjects with nSLE and NPSLE, respectively. Both SLE groups showed a significant impairment compared with controls on tasks assessing verbal and non-verbal long-term memory, and visuoconstructional abilities. In addition, NPSLE patients reported worse performances than both nSLE patients and controls on task evaluating short-term visuospatial memory. NPSLE subjects were significantly more anxious and depressed compared to both nSLE subjects and controls. By multivariate analysis, only depression levels, among clinical variables, significantly predicted cognitive performance. This study shows that cognitive impairment occurs frequently in both nSLE and NPSLE subjects. The higher frequency in NPSLE may be related to coexisting depressive disturbances.

Simple reaction time to lateralized visual stimuli is not related to the hemispheric side of lesion.

The effect of a single brain lesion on Reaction Times (RTs) to unpatterned visual stimuli was studied in 20 right brain-damaged (RBD) and 19 left brain-damaged (LBD) patients with single small vascular lesions confined to one hemisphere and free of visual field defects and of significant neuropsychological abnormalities (e.g. aphasia or hemineglect). The stimulus was presented in the field either ipsilateral or contralateral to the brain lesion. The stimulus location was either blocked in each hemifield or randomly alternating between fields. RTs in RBD patients were not statistically different from RTs in LBD patients. Intrahemispheric site of the lesion also was irrelevant for the lengthening in RTs. Responses to blocked presentations were faster than to random presentations. Responses to the hemifield contralateral to the brain lesion were slower than to ipsilateral hemifield, and the difference was unrelated to the absolute values of RTs. It is concluded, in contrast to other reports, but in agreement with the more recent literature, that there is no hemispheric dominance for RTs.

Localisation of lesions in aphasia: clinical-CT scan correlations in stroke patients.

Ninety right-handed patients with present or past evidence of aphasia following a stroke were given a standard language battery and a CT scan examination. Presence and type of aphasia were correlated with the location and extent of the CT scan lesion. Most of the findings were compatible with the traditional views about the localisation of lesions in aphasia (e.g., anterior lesions in nonfluent aphasias with good comprehension, posterior lesions in fluent aphasia, etc.). The possible explanations for some unexpected findings (e.g., purely anterior lesions in global aphasia, or purely deep lesions in Broca's aphasia) are discussed. It is stressed that in establishing clinico-CT scan correlation, careful consideration must be given to the fact that both aphasia and the underlying lesion evolve with time.

Computer assisted tomography in neuropsychological research: a simple procedure for lesion mapping.

A simple procedure for mapping the brain lesions observed on the CT scan sections onto a standard diagram of the cerebral hemisphere is described in detail, and its utility for neuropsychological research is briefly discussed.

"Transcortical" features of aphasia following left thalamic hemorrhage.

In a series of 14 thalamic hemorrhage documented by Computerized Axial Tomography (CT) scans, aphasia was present in seven out of eight patients with left lesions while it was absent in the six patients with right lesions. In three cases where detailed language testing was performed, aphasia was characterized by reduction of spontaneous speech with semantic paraphasias, preserved repetition and partially defective auditory verbal comprehension. The language disturbance was persistent in two patients, while it recovered spontaneously within four weeks in one patient. The clinical picture in these patients is similar to the classical "transcortical" aphasias, which are usually due to damage of the marginal language areas. It is suggested that the left thalamus contributes to the semantic level of verbal behavior, which is possibly subserved by these areas.

Somesthetic-visual matching disorders in right and left hemisphere-damaged patients.

Forty-nine patients with recent right (RHD) and left (LHD) hemispheric vascular lesions were compared on a task of somesthetic-visual matching of meaningful objects and of meaningless shapes. A selective impairment for shapes was found in RHD subjects, while LHD patients were impaired in object matching. This double dissociation conforms to the classical distinction between apperceptive and associative agnosia, and extends to the somesthetic modality the "double dissociation" between left and right hemispheric lesions and associative and apperceptive recognition disorders, which has been found in other modalities of agnosia.

Resumption of gainful employment in aphasics: preliminary findings.

We report preliminary data on aphasic patients who, in spite of their language problems, have succeeded in finding a reasonably satisfactory occupational resettlement. Patients who: (a) still had a moderate to sever aphasia, (b) had resumed a gainful employment requiring interpersonal communication, were recalled for a check-up and assessed with: (1) a comprehensive aphasia test: (2) a semistructured interview including detailed questioning about the type and reaction to aphasia, the type of work before the onset of aphasia, the type of current work with particular emphasis on the patients' compensatory mechanisms and emotional reactions. Results comprise 10 cases up to date. One case is described in detail. Findings indicate that the ability to resume a gainful occupation is often greater than could be expected on the sole basis of formal language examination. Findings are discussed from a neuropsychological, social and rehabilitation point of view.

Confabulation and delusional misidentification: a four year follow-up study.

We describe a patient, AZ, who showed, in addition to an amnesic syndrome which eventually improved, longstanding confabulation and delusional misidentification following bilateral frontal and right temporal post-traumatic lesions. Confabulation appeared in personal recollections and on long-term verbal memory testing. Misidentification concerned mainly his wife and house. During the four year follow-up AZ's confabulation progressively shrinked so as to become restricted to verbal memory tasks. By contrast, misidentification persisted. General semantic memory was unimpaired throughout, while performance on frontal tests was initially poor and partly improved in time. We argue that confabulation and misidentification, though often intermingled and occurring after similar lesion pattern, should be considered as different neuropsychological entities.

Phonemic identification defect in aphasia.

Eight-four right-handed patients with unilateral hemispheric damage (50 aphasics, 12 non-aphasic left brain-damaged and 22 right brain-damaged patients) and 53 control patients without cerebral lesions were given a test of phoneme identification which examined the S's ability to identify the acoustic boundary between the two phonemes, /d/ and /t/, expressed in terms of voice-onset time (VOT). Phonemic identification defect (PID), defined with reference to the performance of the control group, was found to be virtually limited aphasics; in over 70 per cent of them, the identification of the boundary zone between voiced and voiceless consonants along the VOT continuum was either impossible or abnormal, While neither the fluency - nonfluency dimension of speech nor the level of comprehension seemed to be crucially associated with PID, some evidence pointed to disordered phonemic output as to one dimension of aphasia that is specifically related to it.