Left hemispheric neuronal heterotopia: a PET, MRI, EEG, and neuropsychological investigation of a university student

A 21-year-old left-handed medical student had a prominent unilateral cerebral cortical malformation due to an ontogenetic migration disorder. We performed neuropsychological studies, EEG, T1- and T2-weighted and proton-density MRI, and positron emission tomography (PET) (under both the resting condition and neuropsychological activation). Neuropsychological testing revealed normal intelligence and generally normal memory functioning but selective deficits in tests of verbal fluency and spatial-figural relationships. Proton-density and T2-weighted MRI revealed extensive left cortical heterotopia that included parts of the Wernicke area. PET under the resting condition revealed a small interhemispheric difference with slightly reduced glucose metabolism in the left temporoparietal cortical zone. An activation PET (with the patient performing a verbal fluency test) resulted in a normal overall increase in metabolism but marked deviations in cortical areas. The highest activity changes were in the Broca and Wernicke areas of the right hemisphere, and there was very little activation in those regions of the left hemisphere that were expected to respond well to the activation--the temporal, parietal, and temporo-occipital cortical zones. We conclude that there can be large compensations for unilateral heterotopia.     

Characterization of two rice MADS box genes that control flowering time

This study utilised positron emission tomography (PET) to identify the cortical areas involved in verbal initiation and suppression in normal subjects whilst performing a sentence completion test (the Hayling Test). In the first condition (response initiation) subjects were required to complete a sentence from which the last word was omitted, whereas in the second condition (response suppression) subjects were asked to complete a sentence with a word which made no sense in the context of the sentence. Subjects were also required to perform a control task in which they had to read out the last word of given sentences. Compared to the control task, response initiation was associated with left-sided activation of the frontal operculum, inferior frontal gyrus, middle temporal gyrus and the right anterior cingulate gyrus, whereas response suppression was associated with left frontal operculum, inferior frontal gyrus and right anterior cingulate gyrus activation. The difference in activation between the two conditions of the Hayling Test lay in the increased activation of the left middle temporal gyrus and the left inferior frontal gyrus during response initiation.     

Pitch processing in the human brain is influenced by language experience

Positron emission tomography (PET) was used in a cross-linguistic study to compare pitch processing in native speakers of English, a nontone language, with those of Thai, a tone language. When discriminating pitch patterns in Thai words, only the Thai subjects showed activation in the left frontal operculum. Activation of this region near the classically defined Broca's area suggests that the brain recognizes functional properties, rather than simply acoustic properties, of complex auditory cues in accessing language-specific mechanisms in pitch perception.     

Task-related activations in heterotopic brain malformations: a PET study

Positron emission tomography (PET) studies have shown normal or elevated levels of glucose metabolism in neuronal heterotopia, raising the issue of potential participation of heterotopic neurons in cognitive processing. We studied three patients with heterotopic malformations, using [(15)O]water PET and experimental conditions selected according to the location of the malformations. Task performance was associated with blood flow increases of > 17% within the heterotopia in each patient. In two, these occurred in left frontal heterotopia during sentence generation. In the third patient, activations for facial and visuospatial discrimination and picture naming were found in a right posterior heterotopion. Our findings may reflect participation of heterotopia in cognitive function and suggest that heterotopic neurons synapse with neurons in other brain regions.     

Differential responsiveness of murine T lymphomas to local growth and invasion factors may determine metastasis formation in the ovaries

Iodine-123-metaiodobenzylguanidine [123I-MIBG] has been used to evaluate the cardiac sympathetic nervous system. We evaluated the effect of pulmonary hypertension on the sympathetic neuronal function of the left ventricle in patients with pulmonary hypertension. We studied 20 patients with either chronic lung disease or pulmonary vascular disease. The patients were divided into a pulmonary hypertensive group and a control group. Single photon emission tomography was performed in the resting state 15 min and 4 h after administration of 123I-MIBG. Regions of interest (ROI) were set in the left ventricular (LV) free wall, the interventricular septum (IVS) and outside the LV free wall on short-axis images. The washout rate and the ROI/LV uptake ratio were calculated in each ROI. The IVS:LV uptake ratio was significantly lower in the pulmonary hypertensive group than in the control group. Our results suggest that left heart sympathetic neuronal dysfunction initially occurs in the IVS before it involves the LV free wall subsequently.     

Suppressed UDP-galactose: ceramide galactosyltransferase and myelin protein mRNA in twitcher mouse brain

To investigate the role of temporal processing in language lateralization, we monitored asymmetry of cerebral activation in human volunteers using positron emission tomography (PET). Subjects were scanned during passive auditory stimulation with nonverbal sounds containing rapid (40 msec) or extended (200 msec) frequency transitions. Bilateral symmetric activation was observed in the auditory cortex for slow frequency transitions. In contrast, left-biased asymmetry was observed in response to rapid frequency transitions due to reduced response of the right auditory cortex. These results provide direct evidence that auditory processing of rapid acoustic transitions is lateralized in the human brain. Such functional asymmetry in temporal processing is likely to contribute to language lateralization from the lowest levels of cortical processing.     

Language and motor functions activate calcified hemisphere in patients with Sturge-Weber syndrome: a positron emission tomography study

This study examines whether or not in Sturge-Weber syndrome hypoperfused brain areas that are affected by calcification continue to retain some function and participate in language and motor activations. [15O]-Water positron emission tomography (PET) was used for brain mapping of these functions in two patients with extensive unilateral calcification and hypoperfusion and in one patient with calcification and hypoperfusion restricted to the left posterior region. Task-related regional cerebral blood flow changes suggest that (1) hypoperfused areas may become activated during language and motor performance, and (2) progressive calcification in Sturge-Weber syndrome is associated with functional reorganization in the language and motor domains. Interhemispheric reorganization appears to be more pronounced for language than for motor functions.     

Cerebral interregional correlations of associative language processing: a positron emission tomography activation study using fluorine-18 fluorodeoxyglucose

Even though there have been numerous positron emission tomography (PET) activation studies on the perfusional and metabolic bases of language processing, little is known about the intracerebral functional network of language and cognitive processes. It was the aim of this study to investigate the cerebral interregional correlations during voluntary word association versus word repetition in healthy subjects to gain insight into the functional connectivity of associative speech processing. Due to individual variability in functional anatomy, the study protocol was designed as an averaged single-subject study. Eight healthy volunteers performed a verbal association task during fluorine-18 fluorodeoxyglucose (18F-FDG) PET scanning. Two different tasks were performed in randomized order: (a) word repetition (after auditory presentation of nouns) as a control condition, and (b) word association (after auditory presentation of nouns) as a specific semantic activation. The regional metabolic rate of glucose (rMRGlu) was calculated after brain regionalization [112 regions of interest on individual 3D flash magnetic resonance imaging (MRI)] and PET/MRI realignment. Statistical analysis was performed for comparison of association and repetition and for calculation of interregional correlation coefficients during both tasks. Compared with word repetition, word association was associated with significant increases in rMRGlu in the left prefrontal cortex, the left frontal operculum (Broca's area) and the left insula, indicating involvement of these areas in associative language processing. Decreased rMRGlu was found in the left posterior cingulum during word association. During word repetition, highly significant negative correlations were found between the left prefrontal cortex, the contralateral cortex areas and the ipsilateral posterior cingulum. These negative correlations were almost completely eliminated during the association task, suggesting a functional decoupling of the strict intercorrelation pattern.     

Unilateral pigmentary degeneration of the retina associated with heterochromia iridis

BACKGROUND: For the past 5 years, a 56-year-old patient has been displaying monocular progressive pigmentary changes in the left eye. Heterochromy of the left eye has been known since childhood. The other eye is clinically and functionally normal. The patient was adopted and he has no children. Therefore, we have no family history. METHODS: The patient was examined clinically and by means of electroretinography, electrooculography, perimetry, computer tomography, pulsatile ocular blood flow (POBF) measurement, serology and Doppler sonography. RESULTS: Electrophysiology displayed a considerable reduction of scotopic and photopic ERGs, a reduced dark-through, and a reduced light-rise in the left eye, whereas the fellow eye was normal. The visual field was limited to 5 deg around the fixation point, and a peripheral crescent-shaped arch encircled the temporal-inferior quadrant concomitant to the pigmentary changes. By computer tomography and Doppler sonography a vascular affection was excluded. The left eye displayed lower POBF values. All serological tests were found negative. CONCLUSION: The clinical picture and negative exclusion criteria indicate a unilateral retinitis pigmentosa. However, with regard to the literature an unequivocal diagnosis can only be made upon hereditary evidence.     

A novel simple method for quantifying bacteria from endotracheal aspirates

Two children with neuronal migration disorders and unexpectedly mild clinical symptoms are reported. The first patient was followed with the diagnosis of febrile convulsion and seizures associated with fever for 14 years. Computed tomography scans were normal. Although periodic slow waves of the left parietal cortex were detected on the first two electroencephalograms, his latest examination was normal. Magnetic resonance imaging performed at 16 years of age disclosed a left parietal schizencephaly extending between the parietal cortex and corpus callosum. The second patient was followed with the diagnosis of febrile convulsion for 2 years and later experienced afebrile seizures. On his latest visit, a posterior parietal pachygyric region and a parieto-occipital island heterotopia on the left hemisphere were diagnosed by magnetic resonance imaging. We believe that review of these patients, at the mildest end of the clinical spectrum of neural migration disorders, will contribute to a new understanding of the correlation between clinical and pathologic findings of neuronal migration disorders.     

The role of luminal bacteria in colitis: more than an antigenic drive

Cardiac hemangioma is a rare benign vascular tumor. A 44-year-old woman with hemangioma arising from the left atrium and transient atrial fibrillation is reported. Echocardiography, computed tomography and magnetic resonance imaging suggested a hypervascular tumor with clear borders in the pericardial cavity. Selective coronary angiography demonstrated feeding arteries arising from the right and left circumflex coronary arteries. Under cardiopulmonary bypass the tumor was successfully resected. Pathological examination showed a cavernous hemangioma. There is no evidence of recurrence and the patient is doing well three years after the operation.     

Does the cerebellum contribute to cognitive aspects of speech production? A functional magnetic resonance imaging (fMRI) study in humans

Several positron emission tomography (PET) studies suggest a contribution of the lateral aspects of the right cerebellar hemisphere to higher-level (cognitive) aspects of speech production such as controlled verbal response selection. As an alternative, however, 'inner speech', giving rise to subliminal activity of orofacial and laryngeal muscles, might account for the observed activation effects. Eighteen subjects underwent functional magnetic resonance imaging (fMRI) during continuous silent recitation of the names of the months of the year ('automatic speech'). The right cerebellar hemisphere showed a significantly increased hemodynamic response concomitant with, among others, an asymmetric activation pattern towards the left side at the level of the motor strip. Since highly overlearned word strings, presumably, pose few demands on controlled response selection and since the projections of the right cerebellar hemisphere to the left precentral gyrus participate in motor control, the observed cerebellar activation, thus, seems to be related to the articulatory level of speech production rather than, as suggested by previous PET studies, to cognitive operations.     

Pulsatile tinnitus associated with a high jugular bulb and slow venous blood flow

A case of permanent pulsatile tinnitus of the left ear in a patient with hypertriglyceridemia is reported. The combined radiological study with computed tomography, magnetic resonance imaging, and digital angiography excluded a glomus tumor and revealed an enlarged, high-position jugular bulb with slow blood flow. Causes of pulsatile tinnitus are discussed. We conclude that imaging techniques play a major role in the diagnosis of head and neck vascular abnormalities.     

Right atrial metastatic melanoma in a patient with transient ischemic attacks

A 65-year-old-man was admitted for evaluation of a transient ischemic attack. A 4.5 x 5.3-cm right atrial mass and a patent foramen ovale were identified by echocardiography. A 0.5-cm lesion was identified in the left temporal lobe of the brain by magnetic resonance imaging. Positron emission tomography was used to differentiate a tumor from an infarct in the brain. The cardiac and the brain lesions were successfully resected. Histopathologic study of the atrial and cerebral tissue demonstrated that these were metastases from a previously excised scalp desmoplastic malignant melanoma. The patient remains well at 14 months' follow-up.     

Retinal dystrophy in long chain 3-hydroxy-acyl-coA dehydrogenase deficiency

We report a case of Bellini duct carcinoma of the left kidney with invasive growth pattern. A 39-year-old man was admitted to our hospital with the chief complaint of gross hematuria. Ultrasonography showed left renal swelling but normal reniform configuration of the kidney was maintained. Computed tomography demonstrated a low density tumor infiltrating into the renal cortex and with tumor extension into the renal vein. Renal angiography revealed a hypovascular tumor. We suspected a left renal cell carcinoma with tumor extension into the left renal vein, and performed radical nephrectomy. Macroscopically, the resected kidney had a normal outer contour. The tumor with infiltrative growth pattern existed in renal medulla. Histopathologic examination revealed a papillary adenocarcinoma originated in Bellini duct (pT3bN2M0). The patient underwent systemic chemotherapy (M-VAC). This case showed invasive growth pattern, which were different from the usual renal cell carcinoma and Bellini duct carcinoma.     

The neuropsychology of the prefrontal cortex

Single photon emission computed tomography with the xenon inhalation technique is used to compare activation of regional cerebral blood flow in frontal brain regions during the performance of four widely used neuropsychological tests: the Continuous Performance Test, the Wisconsin Card Sorting Test, the Tower of London, and Porteus Mazes. Healthy normal volunteers performing these tasks show significant increases in frontal regions during the Continuous Performance Test, the Wisconsin Card Sorting Test, and the Tower of London, but not the Porteus Mazes. Activation produced by the Continuous Performance Test and the Tower of London are mesial and bilateral and may reflect stimulation of midline attentional circuits. The Wisconsin Card Sorting Test produces a left dorsolateral area of prefrontal activation. These findings indicate that regional activation of the frontal lobes occurs in response to cognitive challenges produced through performance of standard neuropsychological tests.     

Movement-related potential measures of different modes of movement selection in Parkinson's disease

Movement-related potentials were recorded preceding self-paced voluntary movements in patients with Parkinson's disease and in healthy subjects of the same age group. We compared the Readiness Potential preceding joystick movements in a fixed direction and preceding joystick movements in freely selected directions. In normal subjects the Readiness Potential amplitude was higher preceding freely selected movements than preceding movements in a fixed direction. The Readiness Potential in Parkinson patients failed to be modified by the different modes of movement selection. The modulation of the Readiness Potential by different ways of preparing for movement might be due to the supplementary motor area (SMA) being more strongly engaged by tasks requiring internal control of movements than by tasks that are externally structured. The results suggest that this task-dependent variation of SMA activity is reduced in Parkinson's disease. A failing capacity to adapt SMA activity to different task demands has previously been suggested by evidence from positron emission tomography studies using similar tasks.     

The cost-effectiveness of a clinical pharmacist intervention among elderly outpatients

We report the close correlation between changes in serum immunoreactive vascular endothelial growth factor 165 (iVEGF165) levels and metastatic tumor burden measured by computed tomography scan before treatment, during the antitumor response, and during early progression in a patient treated with ex vivo gene therapy for renal cell carcinoma. With the researcher blinded to outcome, iVEGF levels were measured in archived serum samples from a patient with metastatic renal cell carcinoma who demonstrated a 7-month partial remission to treatment with autologous, irradiated human GM-CSF gene transduced tumor vaccine. Although a spontaneous regression could not be formally excluded in this patient, the appearance of 20 new pulmonary metastases on computed tomography scan after nephrectomy and before vaccination indicates that if spontaneous regression occurred, it took place at the start of vaccine treatment.     

Localised neuronal migration disorder and intractable epilepsy: a prenatal vascular aetiology

Localised neuronal heterotopias are an increasingly recognised cause of intractable focal epilepsies. The aetiology of these circumscribed disorders of neuronal migration is often unknown although in some instances proximity to areas of prenatal infarction suggests that severe ischaemia was responsible. A patient is described with intractable complex partial seizures associated with heterotopic grey matter and cerebral hypoplasia confined to the territory of the left posterior cerebral artery; the left hippocampus was spared. Angiography showed a normal left anterior choroidal artery but a hypoplastic left posterior cerebral artery, implicating prenatal ischaemia without frank infarction as the aetiology of the malformation.     

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography. J. Neurophysiol. 80: 3326-3330, 1998. Stimulation of the somatosensory thalamus was used for more than 2 decades to treat chronic pain in the human. However, despite clinical reports of successful results, little is known about the actual mechanisms mediating this form of stimulation-produced analgesia. To reveal possible neuronal pathways evoked by thalamic stimulation, we measured regional changes in cerebral blood flow (rCBF) in five patients who received successful long-term relief of chronic pain with somatosensory thalamic stimulation. Positron emission tomography during thalamic stimulation revealed significant activation of the thalamus in the region of the stimulating electrodes as well as activation of the insular cortex ipsilateral to the thalamic electrodes (contralateral to the patients' clinical pain). For these patients, thalamic stimulation also evoked paresthesiae that included thermal sensations in addition to tingling sensations. Results of this study indicate that in some cases somatosensory thalamic stimulation may activate a thalamocortical pain modulation circuit that involves thermal pathways. These results are consistent with other recent reports suggesting that activation of thermal pathways may contribute to modulation of nociceptive information.