The contribution of white and gray matter differences to developmental dyslexia: insights from DTI and VBM at 3.0 T.

Developmental dyslexia is one of the most common neuropsychological disorders in children and adults. Only few data are available on the pathomechanisms of this specific dysfunction, assuming--among others--that dyslexia might be a disconnection syndrome of anterior and posterior brain regions involved in phonological and orthographic aspects of the reading process, as well as in the integration of phonemes and graphemes. Therefore, diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) were used to verify the hypothesis of altered white and gray matter structure in German dyslexic adults. DTI revealed decreased fractional anisotropy (FA) in bilateral fronto-temporal and left temporo-parietal white matter regions (inferior and superior longitudinal fasciculus). Significant correlations between white matter anisotropy and speed of pseudoword reading were found. In dyslexics, gray matter volumes (as measured by VBM) were reduced in the superior temporal gyrus of both hemispheres. So far, our results, based on a combined analysis of white and gray matter abnormalities, provide exceedingly strong evidence for a disconnection syndrome or dysfunction of cortical areas relevant for reading and spelling. Thus, we suggest that this imbalance of neuronal communication between the respective brain areas might be the crucial point for the development of dyslexia.

Brain atrophy in pure and complicated hereditary spastic paraparesis: a quantitative 3D MRI study.

Hereditary spastic paraparesis (HSP) is a heterogeneous group of neurodegenerative disorders with progressive lower limb spasticity, categorized into pure (p-HSP) and complicated forms (c-HSP). The purpose of this study was to evaluate if brain volumes in HSP were altered compared with a control population. Brain volumes were determined in patients suffering from HSP, including both p-HSP (n = 21) and c-HSP type (n = 12), and 30 age-matched healthy controls, using brain parenchymal fractions (BPF) calculated from 3D MRI data in an observer-independent procedure. In addition, the tissue segments of grey and white matter were analysed separately. In HSP patients, BPF were significantly reduced compared with controls both for the whole patient group (P < 0.001) and for both subgroups, indicating considerable brain atrophy. In contrast to controls who showed a decline of brain volumes with age, this physiological phenomenon was less pronounced in HSP. Therefore, global brain parenchyma reduction, involving both grey and white matter, seems to be a feature in both subtypes of HSP. Atrophy was more pronounced in c-HSP, consistent with the more severe phenotype including extramotor involvement. Thus, global brain atrophy, detected by MRI-based brain volume quantification, is a biological marker in HSP subtypes.

Topography of cerebral atrophy in early Huntington's disease: a voxel based morphometric MRI study.

OBJECTIVES: To analyse grey matter changes in early stages of Huntington's disease using magnetic resonance imaging (MRI) and the technique of voxel based morphometry (VBM). METHODS: Forty four patients with a molecularly confirmed clinical diagnosis of Huntington's disease based on the presence of motor signs were included in the study. Patients were clinically rated using the Unified Huntington's Disease Rating Scale; all were in early clinical stages of the disease (that is, Shoulson stages I and II). High resolution volume rendering MRI scans (MP-RAGE) were acquired. MRI data were volumetrically analysed in comparison to an age matched normal database by VBM, using statistical parametric mapping (SPM99). RESULTS: In Huntington's disease, robust regional decreases in grey matter density (p<0.001, corrected for multiple comparisons)-that is, atrophy-were found bilaterally in striatal areas as well as in the hypothalamus and the opercular cortex, and unilaterally in the right paracentral lobule. The topography of striatal changes corresponded to the dorso-ventral gradient of neuronal loss described in neuropathological studies. Stratification according to clinical severity showed a more widespread involvement extending into the ventral aspects of the striatum in the group of more severely affected patients. CONCLUSIONS: The topography of cerebral volume changes associated with Huntington's disease can be mapped using VBM. It can be shown that cerebral grey matter changes co-vary with clinical severity and CAG repeat length.

Positron emission tomography in female patients with borderline personality disorder.

The pathology of Borderline personality disorder (BPD) is poorly understood and its biological basis remains largely unknown. One functional brain imaging study using [(18)F]Deoxyglucose-PET previously reported frontal and prefrontal hypometabolism. We studied brain metabolism at baseline in 12 medication-free female patients with BPD without current substance abuse or depression and 12 healthy female controls by [(18)F]Deoxyglucose-PET and statistical parametric mapping. We found significant frontal and prefrontal hypermetabolism in patients with BPD relative to controls as well as significant hypometabolism in the hippocampus and cuneus. This study demonstrated limbic and prefrontal dysfunction under resting conditions in patients with BPD by FDG-PET. Dysfunction in this network of brain regions, which has been implicated in the regulation of emotion, may underlie symptoms of BPD.

Different striatal dopamine D2 receptor occupancy in alcohol dependent patients with or without physical withdrawal symptoms --a study using IBZM-SPECT.

Ten male patients with type I alcohol dependency fulfilling DSM-IV criteria for alcohol dependency were investigated twice using IBZM-SPECT after alcohol withdrawal (day 2 and day 28 after withdrawal). Five patients had a history of physical withdrawal symptoms, 5 patients had no such history. The group with physical withdrawal symptoms showed higher IBZM binding in both scans indicating differences of dopaminergic neurotransmission in different subtypes of alcohol dependency.

Hashimoto encephalopathy - is it underdiagnosed in pediatric patients?

Hashimoto encephalopathy (HE) is associated with Hashimoto thyroiditis. Clinically it presents with variable symptoms like seizures, neuropsychiatric changes or focal neurological deficits. Autoimmune phenomena are hypothesized for the pathogenesis. HE has mainly been described in the adult population. We present two 14-year-old patients who presented with recurrent seizures and mental decline. SPECT and PET scans showed distinctly pathological changes. Both patients were diagnosed with HE and improved dramatically on steroids. We feel that HE is a rare but important differential diagnosis of encephalopathy also in the pediatric population. As this disease responds well to steroids, we recommend to obtain basic thyroid function tests as well as thyroid antibodies in all cases of unexplained encephalopathy or unexplained status epilepticus.

Depressive state and regional cerebral activity in cancer patients - a preliminary study.

BACKGROUND: The aim of this study was to investigate influences of depressive states, chemotherapy and existence of remaining tumors on the regional brain activity of cancer patients. MATERIAL AND METHODS: Positron emission tomography with 18F-fluorodeoxyglucose was performed on 21 patients with various types of cancer. Their brain images were compared to 10 age- and gender-matched control data using statistical parametric mapping (SPM). The patients were subgrouped into the with and without depression based on the scores on Zung's self-rating depression scale (SDS), with and without previous chemotherapy, and with and without existence of remaining tumors. RESULTS: Significant metabolic reduction was detected in the cingulate gyrus, prefrontal, dorsolateral prefrontal, temporoparietal cortices and basal ganglia in cancer patients. These findings were close to known lesions of major depression. Intra-group comparisons showed that these hypometabolic findings were associated with the depth of depressive state. Influences of chemotherapy and remaining tumors on the cerebral cortex seemed to be weaker than that of psychological factors. CONCLUSIONS: The present pilot study suggests that frontal hypoactivity commonly seen in cancer patients is likely to be associated with depression rather than chemotherapy or remaining tumors. A brain mapping technique might be useful in evaluating neuropsychiatric problems in cancer patients.

[Diagnosis of questionable mandibular infiltration by squamous epithelial carcinomas. 3-D 99mTc-DPD SPECT reconstruction and (18F) fluoride PET study: diagnostic advantages or unnecessary expense?]. / Diagnostik fraglicher Unterkieferinfiltrationen durch Plattenepithelkarzinome. 3-D-99mTc-DPD-SPECT-Rekonstruktion und [18F]-Fluorid-PET-Untersuchung: diagnostischer Vorteil oder übertriebener Aufwand?

OBJECTIVE: A prospective study was designed to compare computer-aided 3D 99mTc-DPD SPECT reconstruction, conventional 99mTc-DPD SPECT investigation (n = 88) and flurine-18 PET (n = 10) in the assessment of mandibular bone invasion by SCC. PATIENTS/METHODS: Between 10/97 and 03/00 88 patients with SCC of the mandibular region were enrolled in this study. In 50 cases mandibular resection (segmental or marginal) was performed basing on the pretherapeutic diagnostic results. RESULTS: No differences could be found between 3D 99mTc-DPD SPECT reconstruction and conventional 99mTc-DPD SPECT investigation. Both techniques revealed the same high sensitivity (100%) and the same specificity of 91.6 (efficiency 95.4%). Flurine-18 PET showed a sensitivity of 100%, but specificity only reached 50% (efficiency 60.0%). CONCLUSIONS: This investigation does not provide evidence that the financial and time consuming techniques of computer-aided 3D 99mTc-DPD SPECT reconstruction and flurine-18 PET show advantages compared to conventional 99mTc-DPD SPECT investigation in the assessment of mandibular invasion by SCC.

Hypermetabolism in the ventrolateral thalamus in unilateral Parkinsonian resting tremor: a positron emission tomography study.

Tremorogenesis in Parkinson's disease (PD) is assumed to involve a cerebral network including the thalamus. An imaging study was performed on eight PD patients with strictly unilateral resting tremor using fluorodeoxyglucose positron emission tomography coregistered to 3-dimensional magnetic resonance imaging. Increased metabolic activity of high statistical significance (P<0.001) was found in the anterior ventrolateral nuclear group of the thalamus located contralateral to the tremor side. The metabolic changes significantly covaried with tremor amplitudes. For the first time, it could be demonstrated that thalamic metabolic changes associated with tremor in PD are localized in the ventral lateral anterior nucleus (VLa). The results are discussed with respect to previous studies on tremor generation.

Limbic encephalitis investigated by 18FDG-PET and 3D MRI.

Two patients with clinically probable or possible limbic encephalitis (LE) are reported, both cases with typical findings in clinical symptoms (severe neuropsychological deficits and complex partial seizures) and in routine magnetic resonance imaging (MRI) (hyperintense mesiotemporal lesions). Underlying malignancy was identified (rectal carcinoma) in one case but could not be detected in the other patient. The 2 patients were investigated by cerebral 18F-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) and 3-dimensional (3D) MRI, and abnormalities in metabolic activity were mapped using coregistration of spatially normalized PET and MRI. Highly significant focal hypermetabolism in bilateral hippocampal areas was found in both cases. The authors' findings support FDG-PET coregistered to 3D MRI as a potentially valuable additional tool in the imaging diagnostics of LE. Results are discussed with respect to the clinical symptoms and previously reported imaging findings in the disease.

Evaluation of microvascular bone graft reconstruction of the head and neck with 3-D 99mTc-DPD SPECT scans.

OBJECTIVE: We conducted a prospective investigation to evaluate the diagnostic accuracy of computer-aided 3-dimensional (3-D) technetium 99m dicarboxypropane methylene diphosphonate ((99m)Tc-DPD) single photon emission computed tomography (SPECT) reconstruction in the evaluation of microvascular bone flaps used for maxillofacial reconstruction. STUDY DESIGN: Twenty patients who received 20 autogenous microvascular bone flaps for reconstruction of the mandible and maxilla were evaluated. Forty bone scans with subsequent computer-aided reconstruction were performed. Each graft could be assessed within 48 to 72 hours after surgery. The second bone scan was performed between 12 and 14 days after surgery. RESULTS: Complications were observed in 5 grafts. SPECT investigation performed at the 2 time points after reconstruction showed a significantly higher tracer uptake in grafts with an uncomplicated further course than in those that developed complications. CONCLUSIONS: Computer-aided 3D (99m)Tc-DPD SPECT reconstruction serves as a useful prognostic tool and helps in the very early recognition of complications. This technique adds significantly to the value of planar bone scintigraphy and conventional SPECT images.

Combined semantic dementia and apraxia in a patient with frontotemporal lobar degeneration.

In this study we report neuropsychological and brain-imaging findings in a patient with frontotemporal lobar degeneration. Brain imaging using registration of (18)fluorodeoxyglucose (FDG)-PET data to three-dimensional (3-D) magnetic resonance imaging showed atrophy and highly significant hypometabolism of the left temporal lobe and both frontal lobes. Volumetric measurements of the hippocampi/amygdala showed a reduction in volume of 25% on the left compared to right within cortical areas. Neuropsychological testing revealed semantic dementia with severe anomia as well as apraxia with impairment of both recognition and production of motor acts. The implications of this case of early manifestation of frontotemporal lobar degeneration for our knowledge of dementia are discussed.

Alterations of cerebral glucose metabolism indicate progress to severe morphological brain lesions in neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (SLE) is frequently associated with deficits in brain glucose metabolism, even if morphological imaging by magnetic resonance imaging (MRI) shows no abnormalities. In these patients it is unclear whether or not the changes of brain metabolism measured by F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) may progress to lesions of cerebral structure. We describe a 20-year-old woman with SLE who presented with depression, headache and impairment of memory. Initially, a cranial MRI was negative, but FDG-PET revealed significant hypometabolism in the frontal and parieto-temporo-occipital regions on both sides as well as hypermetabolism in the nuclei caudati. Within two months the patient developed an acute confusional state, seizures, visual disturbances and cranial MRI became positive showing hyperintensities at the basal ganglia and the temporo-occipital regions. Focal cerebral symptoms responded to treatment with high dose corticosteroids and brain lesions in MRI disappeared. However, a second FDG-PET showed persistent hypometabolism at frontal regions in accordance with the persistence of subclinical depression. To our knowledge, this is the first SLE case report showing that functional brain lesions visualized by FDG-PET may be a risk factor for subsequent structural brain damage seen in MRI. Thus, FDG-PET may help to verify cerebral involvement of SLE earlier than MRI.

Neuro-Behçet's syndrome in a patient not fulfilling criteria for Behçet's disease: clinical features and value of brain imaging.

Central nervous system involvement is rarely an initial presenting manifestation of Behçet's disease (BD). We report the case of a 33-year-old man with recurrent attacks of fever, oral mucosal ulcers, deep venous thrombosis, diplopia, vertigo and headache. Sequential brain magnetic resonance imaging (MRI) scans showed fluctuating lesions of the brain stem, mesencephalon and thalamus. F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) revealed hypometabolism at the parieto-occipital cortex at both sides and the brain stem. Treatment with prednisone and cyclosporine A led to a complete remission and normalisation of MRI and FDG-PET lesions. The present case illustrates the difficulty in the differential diagnosis of early neuro-BD.

Reproducibility of PET brain mapping of cancer patients.

Twenty German cancer patients (56.9+/-12.7 years old) without brain metastasis underwent neurological PET. The acquired brain data were compared to the data of ten age and sex-matched controls (53.6+/-15. 7). Scores of Zung's Self-rating Depression Scale (SDS) obtained from 15 out of the 20 patients suggested they might be mildly depressed. Scores of Taylor's Manifest Anxiety Scale (MAS), used for additional psychological evaluation, were close to normal distribution. Hypometabolic areas in the German cancer patients were compared with those demonstrated in our previous study in Japanese cancer patients. Common findings in both studies were observed in the limbic structures, such as the anterior and posterior cingulate gyri, the basolateral frontal cortices, as well as in the basal ganglia (especially the caudate nucleus) and frontal cortex. These results are in accordance with many previous PET studies on major depression. The results show that the positron emission tomography and (18)F-fluoro-deoxyglucose ((18)FDG-PET) brain mapping results could be partially reproduced, and suggest that PET brain mapping of cancer patients has a potential clinical application to the field of psycho-oncology and cancer patient care.

[3D SPECT reconstruction - a diagnostic method in oral and maxillofacial surgery]. / 3-D-SPECT-Rekonstruktion zur Diagnostik in der Mund-, Kiefer- und Gesichtschirurgie.

Computer-aided three-dimensional (3D) reconstruction of conventional (99m)Tc-DPD SPECT data was used for basic investigations of different disease entities of the orofacial area, with the aim of improving primary diagnosis and, in selected cases such as microvascular bone reconstruction, for a more comprehensive control after therapy. So far, the new 3D technique has been applied in 49 patients with different indications based on commonly acquired sets of data without any further hazard for the patients. In comparison to conventional planar scintigrams, the advantage of this sophisticated technique is a higher image contrast and a clear-cut signal of the investigated bone areas without any superimposing effects. Therefore, the anatomical description of the process is better, which is particularly important in cases of osteomyelitis and after microvascular reconstruction of skull bone defects. In addition, the follow-up investigations can assess treatment results far better and outcome predictions are much more reliable. A higher sensitivity and specificity in cases of squamous cell carcinoma as regards bone infiltration could not be achieved so far. In summary, computer-aided 3D reconstruction of conventionally acquired (99m)Tc-DPD-SPECT data represents a significant improvement in radionuclide imaging technique, providing a much better diagnostic interpretation of selected disease entities in the oral and maxillofacial area.