A role for accelerometry in the differential diagnosis of tremor syndromes.

Accelerometry is a reliable tool for gauging the occurrence, amplitude and frequency of tremor. However, there is no consensus on criteria for accelerometric diagnosis of tremor syndromes. We enrolled 20 patients with essential tremor (ET), 20 with dystonic tremor (DT), and 20 with classic parkinsonian tremor (PD-T), all meeting accepted clinical criteria. All the patients underwent dopamine transporter imaging (by means of single-photon emission computed tomography) and triaxial accelerometric tremor analysis. The latter revealed groupwise differences in tremor frequency, peak dispersion, spectral coherence, unilaterality and resting vs action tremor amplitude. From the above, five diagnostic criteria were extrapolated for each condition. Receiver operating characteristic curves, depicting criteriabased scoring of each tremor type, showed negligible declines in specificity for scores ≥4 in patients with ET or DT and scores ≥3 in patients with PD-T, thus providing a simple scoring method (accelerometrically derived) for differential diagnosis of the principal tremor syndromes.

DJ-1 modulates mitochondrial response to oxidative stress: clues from a novel diagnosis of PARK7.

DJ-1 mutations are associated to early-onset Parkinson's disease and accounts for about 1-2% of the genetic forms. The protein is involved in many biological processes and its role in mitochondrial regulation is gaining great interest, even if its function in mitochondria is still unclear. We describe a 47-year-old woman affected by a multisystem disorder characterized by progressive, early-onset parkinsonism plus distal spinal amyotrophy, cataracts and sensory-neural deafness associated with a novel homozygous c.461C>A [p.T154K] mutation in DJ-1. Patient's cultured fibroblasts showed low ATP synthesis, high ROS levels and reduced amount of some subunits of mitochondrial complex I; biomarkers of oxidative stress also resulted abnormal in patient's blood. The clinical pattern of multisystem involvement and the biochemical findings in our patient highlight the role for DJ-1 in modulating mitochondrial response against oxidative stress.

Imaging studies on dopamine transporter and depression: a review of literature and suggestions for future research.

We review the conflicting results from imaging studies of dopamine transporter availability in depressed patients and also discuss the heterogeneity of the variables involved. Major depression includes diverse clinical manifestations and in recent years there has been an increasing interest in the identification of homogeneous phenotypes and different clinical subtypes of depression, e.g. anhedonic depression, retarded depression, etc. In addition, the use of different radioligands and imaging techniques, diverse rating scales, together with the lack of control of clinical variables (clinical course, recent or past use of substances of abuse, etc.) make it difficult to clearly identify neuronal regions or networks with consistently abnormal structures or functions in major depressive disorder. It is probably necessary to build a shared approach between clinicians and researchers in order to identify standardized procedures to better understand the role of the dopamine transporter in depression. We outline a list of major issues and also suggest some standardized procedures in collecting clinical and imaging data on major depressed patients. Our aim is to delineate a possible "modus operandi" that would be a proposal for neuroreceptor studies on major depression.

Role of auditory brain function assessment by SPECT in cochlear implant side selection.

Pre-surgery evaluation, indications for cochlear implantation and expectations in terms of post-operative functional results remain challenging topics in pre-lingually deaf adults. Our study has the purpose of determining the benefits of Single Photon Emission Tomography (SPECT) assessment in pre-surgical evaluation of pre-lingually deaf adults who are candidates for cochlear implantation. In 7 pre-lingually profoundly deaf patients, brain SPECT was performed at baseline conditions and in bilateral simultaneous multi-frequency acoustic stimulation. Six sagittal tomograms of both temporal cortices were used for semi-quantitative analysis in each patient. Percentage increases in cortical perfusion resulting from auditory stimulation were calculated. The results showed an inter-hemispherical asymmetry of the activation extension and intensity in the stimulated temporal areas. Consistent with the obtained brain activation data, patients were implanted preferring the side that showed higher activation after acoustic stimulus. Considering the increment in auditory perception performances, it was possible to point out a relationship between cortical brain activity shown by SPECT and hearing performances, and, even more significant, a correlation between post-operative functional performances and the activation of the most medial part of the sagittal temporal tomograms, corresponding to medium-high frequencies. In light of these findings, we believe that brain SPECT could be considered in the evaluation of deaf patients candidate for cochlear implantation, and that it plays a major role in functional assessment of the auditory cortex of pre-lingually deaf subjects, even if further studies are necessary to conclusively establish its utility. Further developments of this technique are possible by using trans-tympanic electrical stimulation of the cochlear promontory, which could give the opportunity to study completely deaf patients, whose evaluation is objectively difficult with current audiological methods.

Provoked ictal SPECT in temporal and extratemporal drug-resistant epileptic patients: comparison of Statistical Parametric Mapping and qualitative analysis.

OBJECTIVE: To compare Statistical Parametric Mapping (SPM) with qualitative analysis of provoked ictal SPECT, in terms of both diagnostic yield and efficacy in identifying the epileptogenic zone of temporal and extratemporal epileptic patients. METHODS: We included in the study 27 drug-resistant epileptic patients submitted to provoked ictal SPECT and for whom both SPM and qualitative analysis were obtained. A comparison between visual SPECT analysis and SPM results was performed in terms of lateralization and localization of the ictal hyperperfusion areas. Then, hyperperfusion areas were compared to epileptogenic zones to assess whether they co-localized or not. RESULTS: In twenty patients, a co-localization was found between hyperperfusion areas detected by both qualitative and SPM analysis of provoked ictal SPECT and epileptogenic zones. A concordance between SPM and qualitative analysis in all but two patients was obtained. These findings were observed for both temporal and extratemporal epilepsies. CONCLUSIONS: The co-localization between provoked ictal SPECT hyperperfusion areas and epileptogenic zones found in most patients supports the usefulness of this technique in integrating data provided by neuroimaging and electroclinical correlations to correctly define epileptogenic zone. Moreover, this preliminary work suggests that SPM as entirely objective methodology is feasible and can be accurate also after provoked ictal SPECT.

Meckel's diverticulum findings on Tc-99m red blood cell scintigraphy in a bleeding leukemic patient confirmed by Tc-99m pertechnetate scintigraphy.

A 25-year-old Caucasian woman with a medical history of acute promyelocytic leukemia presented to the emergency department with massive gastrointestinal bleeding. A bone marrow biopsy excluded hemorrhagic leukemia. Esophagogastroduodenoscopy, colonoscopy, emergency abdominal angiography, abdominal CT scan, and wireless capsule endoscopy were performed but no source of bleeding could be detected. Tc-99m RBC scintigraphy was consistent with a small bowel bleeding focus. The persistent and focal images in the right abdomen were suggestive of Tc-99m RBC trapping in the lumen of a Meckel diverticulum (MD). In accordance with this suspicion, successive Tc-99m pertechnetate scintigraphy was performed after 3 days, consistent with the diagnostic hypothesis. Due to the persisting severe bleeding (with a drop in baseline hemoglobin from 10.4 to 7.1 g/dL), despite 8 units of blood transfusion, emergency surgery was performed. Through a minilaparotomy a segmental small bowel resection, including Meckel diverticulum, was performed. The postoperative course was uneventful.

Penicillamine-related lichenoid dermatitis and utility of zinc acetate in a Wilson disease patient with hepatic presentation, anxiety and SPECT abnormalities.

Wilson's disease is an autosomal recessive disorder of hepatic copper metabolism with consequent copper accumulation and toxicity in many tissues and consequent hepatic, neurologic and psychiatric disorders. We report a case of Wilson's disease with chronic liver disease; moreover, in our patient, presenting also with high levels of state anxiety without depression, 99mTc-ECD-SPECT showed cortical hypoperfusion in frontal lobes, more marked on the left frontal lobe. During the follow-up of our patient, penicillamine was interrupted after the appearance of a lichenoid dermatitis, and zinc acetate permitted to continue the successful treatment of the patient without side-effects. In our case the therapy with zinc acetate represented an effective treatment for a Wilson's disease patient in which penicillamine-related side effects appeared. The safety of the zinc acetate allowed us to avoid other potentially toxic chelating drugs; this observation is in line with the growing evidence on the efficacy of the drug in the treatment of Wilson's disease. Since most of Wilson's disease penicillamine-treated patients do not seem to develop this skin lesion, it could be conceivable that a specific genetic factor is involved in drug response. Further studies are needed for a better clarification of Wilson's disease therapy, and in particular to differentiate specific therapies for different Wilson's disease phenotypes.

Auditory cortical activation in severe-to-profound hearing-impaired patients monitored by SPET.

Single photon emission tomography was used to map blood flow increase in temporal and parietal cortex after auditory stimulation in 25 subjects: 10 normal-hearing, 10 severe-profound hearing-impaired and 5 totally deaf. After a 500 Hz pure tone stimulation, a marked perfusion increase was observed, particularly at the level of the contralateral auditory temporal cortex. Blood flow increase in temporal and parietal cortical areas of normal subjects was significantly higher than that observed in severe-to-profound hearing-impaired patients. In all cases, following 500 Hz pure tone acoustic stimulation, the most lateral sagittal slice tomograms (48.75 and 56.25 mm) showed the highest blood flow increase. Statistically significant differences were also observed between normal subjects and hearing-impaired patients in the 48.75 mm sagittal tomogram. In 2 hearing-impaired patients, the single photon emission tomography pattern showed activation of the intermediate sagittal tomogram, suggesting a possible new tonotopic cortical arrangement. No significant activation was present in totally deaf patients. In conclusion, Single Photon Emission Tomography appears to be a useful tool in the evaluation of auditory cortical activation and cortical plasticity, in severe-to-profound hearing-impaired patients. Moreover, it could be a useful test for the study of auditory central pathways.

SPET monitoring of auditory cortex activation by electric stimulation in a patient with auditory brainstem implant.

Auditory cortex activation following multifrequency acoustic stimulation has been evaluated by means of single photon emission tomography (SPET) in one patient before and after an auditory brainstem implant (ABI). No activation could be observed after acoustic stimulation before ABI. After ABI stimulation in the coronal and axial slices, the activation within the temporal cortex contralateral to the stimulated ear was twice (43.76%) that of normal controls (23.94 +/- 2.74%). This marked difference was not present in other selected cortical auditory areas (homolateral temporal, homolateral and contralateral parietal cortices). The temporal cortex was also examined with six consecutive sagittal slices from 18.75 mm up to 56.25 mm lateral to the midline. A very strong activation (51.20%) compared with that of normal controls (9.94 +/- 7.45%) was detected in the 25.26-mm sagittal slice of the temporal cortex contralateral to the stimulated side. The remaining sagittal slices showed an almost normal post-stimulatory activation. As the 25.26-mm sagittal slice corresponds to the medial part of the auditory temporal cortex, its activation suggests that electrode stimulation is concentrated on the region of the cochlear nucleus in which the neurons that transduce high frequencies are located. SPET can be considered useful, in combination with electric auditory-evoked potentials, to obtain information on ABI placement and function, effectiveness of acoustic stimulation, degree of cortical stimulation and tonotopic spatial distribution of auditory cortex activation.

Rhinoscintigraphy: a simple radioisotope technique to study the mucociliary system.

PURPOSE: This was a radioisotope study of nasal mucociliary clearance of total and subtotal nasal obstruction. METHODS: Rhinoscintigraphy was performed by insufflating 1.85 MBq (69 mCi) Tc-99m MAA in 20 patients. Six cases were regarded as the control group, because the presence of small spurs does not affect nasal patency. The remaining 14 patients had various rhinopathic conditions. Two regions of interest were selected, one in the nasal cavity and one in the pharynx. Mucociliary transport speed was calculated. RESULTS: This parameter appeared to be a sensitive index for the assessment of the degree of mucociliary alteration. It showed that polyposis impairs mucociliary transport most severely, thus confirming the results of other published studies. CONCLUSIONS: Rhinoscintigraphy proved to be a reliable, easily reproducible, and harmless method, so it may be used for follow-up examinations in patients who have had surgery of the nose and paranasal sinuses, and for drug therapy of rhinopathic conditions.

Role of nuclear medicine in the diagnosis and therapy of medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) originates in the parafollicular cells (C cells) of the thyroid, secreting both calcitonin and CEA. Genetic and biochemical testing allow early pre-clinical identification of familial forms. Sporadic MTC usually presents as a solitary palpable thyroid nodule and in most cases the definitive diagnosis is established only at the time of surgery. Nuclear medicine procedures, which play a minor role in the preoperative evaluation of MTC, are essential in postoperative follow-up to detect residual and/or recurrent tumor. A number of radiopharmaceuticals are able to visualize MTC lesions with considerable advantages in diagnosis and prognosis, some of them having also a therapeutic role. Among them, 99mTc[V]DMSA shows the highest diagnostic sensitivity and is considered by many authors the radiopharmaceutical of choice in the postoperative work-up of MTC. Radioiodinated MIBG, in spite of its high specificity has a poor sensitivity (30%); however it is useful for the identification of pheochromocytoma and, in patients showing MIBG uptake in tumoral lesions, high activities of 131I-MIBG may be used for therapy. 111In labeled octreotide detects lesions which express somatostatin receptors; a positive scintigraphic result seems to give also prognostic information (higher uptake in slow-growing lesions) and provides the basis for treatment with octreotide or lanreotide and 111In or 90Y-labeled octreotide analogues. Interesting perspectives are offered by 18F-FDG PET and monoclonal anti-CEA labeled antibodies; the latter may be also used for therapy.

Radioiodine therapy in differentiated thyroid carcinoma.

Radioiodine therapy has been successfully applied for over 50 years in the management of differentiated thyroid carcinoma. Careful patient preparation and selection of the optimal dose of radioiodine to be administered are two factors of major importance in the course of management. Main indications for 131I therapy are the ablation of residual thyroid tissue after thyroidectomy, the treatment of locoregional recurrence and distant metastases which involve almost exclusively the lung and bones. A controversial aspect is that of patients with high serum TG levels but negative whole body 131I scintigraphy for whom there is no general agreement. Other controversial aspects involve ablation therapy as the selection of patients to be treated and the control of its efficacy. The cost and possible adverse side-effects of 131I therapy require a careful analysis of prognostic factors in each patient candidate for the treatment.

Diagnostic imaging of euthyroid goiter.

In diffuse or nodular euthyroid goiter, diagnostic imaging is indicated to define, by sonography, the morphology, size and structure of the goiter and to evaluate, by scintigraphy, the regional thyroid function. The instrumental diagnosis of thyroid nodule is essentially based on sonography, scintigraphy and (US-guided) needle aspiration cytology. The evaluation of some sonographic findings (echogenicity, calcification, lesion margins and presence of peripheral ring) may direct to the differentiation of a benign or malignant lesion. The role of color Doppler in the characterization of thyroid nodules is still controversial. Scintigraphy provides information on nodular function, being also the only exam able to show the presence of autonomously functioning thyroid tissue ("hot" nodule), whose diagnosis allows to rule out the presence of thyroid carcinoma with a very strong probability. In intrathoracic goiter, CT and MRI and indicated to show the continuity with the cervical thyroid and to define the relationships with adjacent structures. Radioiodine scintigraphy shows with high (> 90%) diagnostic accuracy the thyroid nature of a mediastinal mass (plunging goiter).

Value of combined approach with thallium-201 single-photon emission computed tomography and Epstein-Barr virus DNA polymerase chain reaction in CSF for the diagnosis of AIDS-related primary CNS lymphoma.

PURPOSE: To determine the diagnostic capability of thallium-201 (201Tl) single-photon emission computed tomography (SPECT) combined with Epstein-Barr virus DNA (EBV-DNA) in CSF for the diagnosis of AIDS-related primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: All human immunodeficiency virus (HIV)-infected patients with focal brain lesions observed between June 1996 and March 1998 underwent lumbar puncture and 201Tl SPECT. Each CSF sample was tested with polymerase chain reaction (PCR) for EBV-DNA. RESULTS: Thirty-one patients were included, 13 with PCNSL and 18 with nontumor disorders. In 11 PCNSL patients, EBV-DNA was positive. Thallium-201 uptake ranged from 1.90 to 4.07 in PCNSL cases (mean, 2.77; 95% confidence interval [CI], 2.35 to 3.19) and from 0.91 to 3.38 in nontumor patients (mean, 1.62; 95% CI, 1.30 to 1.94) (P<.0002). Using a lesion/background ratio of 1.95 as cutoff, a negative SPECT was found in one PCNSL case and 16 nonneoplastic cases. A cryptococcoma and a tuberculoma showed highly increased 201Tl uptake. Epstein-Barr virus DNA was never detected in nonneoplastic patients. For PCNSL diagnosis, hyperactive lesions showed 92% sensitivity and 94% negative predictive value (NPV), whereas positive EBV-DNA had 100% specificity and 100% positive predictive value. The presence of increased uptake and/or positive EBV-DNA had 100% sensitivity and 100% NPV. CONCLUSION: Combined SPECT and EBV-DNA showed a very high diagnostic accuracy for AIDS-related PCNSL. Because PCNSL likelihood is extremely high in patients with hyperactive lesions and positive EBV-DNA, brain biopsy could be avoided, and patients could promptly undergo radiotherapy or multimodal therapy. On the contrary, in patients showing hypoactive lesions with negative EBV-DNA, empiric anti-Toxoplasma therapy is indicated. In patients with discordant SPECT/PCR results, brain biopsy seems to be advisable.

Tonotopic organization of human auditory cortex analyzed by SPET.

Single photon emission tomography (SPET) was used to map blood flow increases in the temporal and parietal cortex of 16 normally-hearing subjects after auditory stimulation. Eight subjects were stimulated with a multifrequency 40 dB HL pure tone at 250, 500, 1000, 2000, 4000 Hz, each frequency varying every 30 s. Single 500 Hz pure tones at 40 dB HL were delivered to the remainder of the subjects. Five bilaterally deaf subjects were used as controls. Marked cerebral flow increase following acoustic stimulation with a significantly prevalent activation of the contralateral temporal cortex was achieved (p < 0.001). According to the tonotopic organization of the human auditory cortex, low monofrequency stimulation activated the most lateral sagittal tomograms (from 48.75 to 56.25 mm laterally to the brain midline) only, while multifrequency stimuli activated all sagittal tomograms (from 18.75 to 56.25 mm). On the basis of these results, it is likely that SPET is able to give real information on the cortical distribution of the auditory frequency range, taking into account the number and position of the activated slices. Further clinical investigations in order to define the relationships among blood flow cortical increases, stimulus intensity and auditory threshold, are in progress.

The contribution of immunoscintigraphy to the diagnosis of head and neck tumours.

Immunoscintigraphy with 111In-F(ab')2-anti-carcinoembryonic-antigen monoclonal antibody was performed in patients with primary head and neck tumours (n = 14), recurrences (n = 3) and suspected posttherapy lymph node metastases (n = 3). No false-positive but two false-negative results were obtained. Single photon emission tomography was performed 24 h after the intravenous administration of the radiopharmaceutical with a positive predictive value of 100% and a sensitivity of 90%. Only two very small (< 1 mm diameter) and necrotic primary tumours escaped detection, while the recurrences and lymph node metastases were always correctly diagnosed, in contrast to computerized tomography and ultrasound. Even though highly selective patients only were considered in the present research, the results do suggest that immunoscintigraphy may be usefully applied in all routine protocols for the study of head and neck cancer.

SPET monitoring of perfusion changes in auditory cortex following mono- and multi-frequency stimuli.

AIM: In order to assess the relationship between auditory cortex perfusion and the frequency of acoustic stimuli, twenty normally-hearing subjects underwent cerebral SPET. METHODS: In 10 patients a multi-frequency stimulus (250-4000 Hz at 40 dB SL) was delivered, while 10 subjects were stimulated with a 500 Hz pure tone at 40 dB SL. The prestimulation SPET was subtracted from poststimulation study and auditory cortex activation was expressed as percent increments. RESULTS: Contralateral cortex was the most active area with multi-frequency and monofrequency stimuli as well. A clear demonstration of a tonotopic distribution of acoustic stimuli in the auditory cortex was achieved. In addition, the accessory role played by homolateral acoustic areas was confirmed. CONCLUSION: The results of the present research support the hypothesis that brain SPET may be useful to obtain semi-quantitative reliable information on low frequency auditory level in profoundly deaf patients. This may be achieved comparing the extension of the cortical areas activated by high-intensity multifrequency stimuli.