Alessandra Serra

Correlation between GABAA receptor density and vagus nerve stimulation in individuals with drug-resistant partial epilepsy

Vagus nerve stimulation (VNS) is an important option for the treatment of drug-resistant epilepsy. Through delivery of a battery-supplied intermittent current, VNS protects against seizure development in a manner that correlates experimentally with electrophysiological modifications. However, the mechanism by which VNS inhibits seizures in humans remains unclear. The impairment of gamma-aminobutyric acid (GABA)-mediated neuronal inhibition associated with epilepsy has suggested that GABA(A) receptors might contribute to the therapeutic efficacy of VNS. We have now applied single photon emission computed tomography (SPECT) with the benzodiazepine receptor inverse agonist [123I]iomazenil to examine cortical GABA(A) receptor density (GRD) before and 1 year after implantation of a VNS device in 10 subjects with drug-resistant partial epilepsy. VNS therapeutic responses resulted significantly correlated with the normalization of GRD. Moreover, a comparable control group, scheduled for a possible VNS implant, failed to show significant GRD variations after 1 year of a stable anti-epileptic treatment. These results suggest that VNS may modulate the cortical excitability of brain areas associated with epileptogenesis and that GABA(A) receptor plasticity contributes to this effect.

Role of SPECT/CT in the preoperative assessment of hyperparathyroid patients

Purpose.Our purpose was to assess the clinical value and additional benefit of fusion single-photon computed tomography (SPECT) and computed tomography (CT) images in locating the parathyroids in a selected group of patients affected by primary (PHP) and secondary hyperparathyroidism (SHP).Materials and methods.Sixteen patients (11 women and five men; age range 35–80 years) with severe hyperparathyroidism (HP) (ten PHP, six SHP) were studied by ultrasound (US), and, after i.v. injection of 370 MBq of 99mTc-sestamibi, by planar parathyroid scintigraphy, SPECT and SPECT/CT using a dualdetector scintillation camera GE Infinia Hawkeye. All patients underwent parathyroidectomy.Results.US findings were inconclusive in 12/16 patients affected by multinodular goitre, and two probable eutopic parathyroid glands were identified. “Double phase” parathyroid scintigraphy identified 14 probable parathyroid glands, SPECT 23 (14 ectopic and nine eutopic) and SPECT/CT confirmed all 23 probable parathyroid lesions, offering more precise localisation and an evident improvement in diagnostic accuracy. Sixteen of these foci of increased uptake were hyperplastic parathyroid glands, six were adenomas, one was a parathyroid carcinoma and one was a thyroid follicular carcinoma. Surgical detection of the 23 sestamibi-positive lesions was correctly matched with 100% of SPECT/CT images and 61% of SPECT data alone. Hybrid imaging thus provided additional data in 39% of lesions, and in three patients with retrotracheal glands, it modified the surgical approach.Conclusions.We believe 99mTc-sestambi SPECT/CT to be a more reliable presurgical method to study a patient subgroup affected by PHP or SHP in whom conventional US and other scintigraphic methods have failed for intrinsic reasons due to the concomitant presence of multinodular goitre or ectopic parathyroid gland. The additional practical benefit derived from this methodology was evident. In fact, anatomical information provided by CT enables precise localisation of the functional abnormalities highlighted by SPECT, and both are essential to a correct surgical approach.

Reversible Pisa syndrome in patients with Parkinson’s disease on dopaminergic therapy

BackgroundThe wide variability of dystonic postures manifested in the clinical course of Parkinson’s disease (PD) represents a complicated on-going issue. Several recently published reports of Pisa syndrome (PS) in parkinsonian patients on dopaminergic therapy have described a variable means of onset and clinical course of this truncal dystonia.ObjectiveTo describe PD patients with PS, with the aim of stressing the frequent iatrogenic origin and potential reversibility of this syndrome during the initial stages of its appearance.Subjects and methodsEight consecutive PD patients who developed a PS after modifications of antiparkinson therapy were studied. All patients underwent detailed clinical assessment, [123I]FP-CIT-SPECT being performed in three cases. Four patients were videotaped.ResultsAll patients developed PS within a variable time-span ranging from 15 days to 3 months after adjustment of treatment. Seven cases of PS were manifested following an increase and one a decrease of dopaminergic treatment. A marked reversal of dystonia was produced in the first seven patients by the withdrawal or dose decrease of dopaminergic PS priming drug, and in the eighth patient an increase of dopaminergic therapy was necessary.ConclusionsIn our opinion, the recognition of reversibility of PS during the initial stages of its appearance may be of considerable clinical importance. Indeed, it may facilitate the rapid withdrawal or reintroduction of dopaminergic treatment, thus avoiding an initial veering towards the subchronic variant and, subsequently into a chronic irreversible variant.

The usefulness of 99mTc-sestaMIBI thyroid scan in the differential diagnosis and management of Amiodarone-induced thyrotoxicosis

BACKGROUND Amiodarone-induced thyrotoxicosis (AIT) is caused by excessive hormone synthesis and release (AIT I) or a destructive process (AIT II). This differentiation has important therapeutic implications. PURPOSE To evaluate (99m)Tc-sestaMIBI (MIBI) thyroid scintigraphy in addition to other diagnostic tools in the diagnosis and management of AIT. SUBJECTS AND METHODS Thyroid and (99m)Tc-MIBI scintigraphies were performed in 20 consecutive AIT patients, along with a series of biochemical and instrumental investigations (measurement of thyrotrophin, free thyroid hormones and thyroid autoantibodies; thyroid colour-flow Doppler sonography (CFDS) and thyroid radioiodine uptake (RAIU)). RESULTS On the basis of instrumental and laboratory data (excluding thyroid (99m)Tc-MIBI scintigraphy) and follow-up, AIT patients could be subdivided into six with AIT I, ten with AIT II and four with indefinite forms of AIT (AIT Ind). (99m)Tc-MIBI uptake results were normal/increased in all the six patients with AIT I and absent in all the ten patients with AIT II. The remaining four patients with AIT Ind showed low, patchy and persistent uptake in two cases and in the other two evident MIBI uptake followed by a rapid washout. MIBI scintigraphy was superior to all other diagnostic tools, including CFDS (suggestive of AIT I in three patients with AIT II and of AIT II in three with AIT Ind) and RAIU, which was measurable in all patients with AIT I, and also in four out of the ten with AIT II. CONCLUSION Thyroid MIBI scintigraphy may be proposed as an easy and highly effective tool for the differential diagnosis of different forms of AIT.

Comparison of MRI, EEG, EPs and ECD-SPECT in Wilson's disease

Objectives – The purpose of this study is to evaluate the efficiency of a few methodologies in detecting anatomo‐functional brain abnormalities in patients with Wilsons disease. Materials and methods – Twenty‐three patients with Wilsons disease underwent almost simultaneously brain magnetic resonance imaging (MRI), computerized electroencephalography (EEG), multimodal evoked potentials (EPs) and ECD single photon computerized tomography (SPECT) evaluation. The clinical picture was of the neurologic type in 8 patients and of the hepatic type in 15. Results – MRI was abnormal in 7 patients with neurological manifestations. The EPs proved pathologic in 7 neurologically symptomatic patients and in 4 cases with hepatic form. These results agree with those reported in other case studies. The EEG records were abnormal only in 3 cases. Nevertheless, the most interesting finding of this study is the particular frequency (86%) of diffuse or focal decrease of ECD uptake shown by brain SPECT. Conclusion – We highlight the use of this interesting procedure in the therapeutic monitoring of this disease.

Brain perfusion abnormalities in patients with euthyroid autoimmune thyroiditis

PurposeBrain perfusion abnormalities have recently been demonstrated by single-photon emission computed tomography (SPECT) in rare cases of severe Hashimoto’s thyroiditis (HT) encephalopathy; moreover, some degree of subtle central nervous system (CNS) involvement has been hypothesised in HT, but no direct evidence has been provided so far. The aim of this study was to assess cortical brain perfusion in patients with euthyroid HT without any clinical evidence of CNS involvement by means of 99mTc-ECD brain SPECT. Sixteen adult patients with HT entered this study following informed consent.MethodsThe diagnosis was based on the coexistence of high titres of anti-thyroid auto-antibodies and diffuse hypoechogenicity of the thyroid on ultrasound in association with normal circulating thyroid hormone and TSH concentrations. Nine consecutive adult patients with non-toxic nodular goitre (NTNG) and ten healthy subjects matched for age and sex were included as control groups. All patients underwent 99mTc-ECD brain SPECT. Image assessment was both qualitative and semiquantitative. Semiquantitative analysis was performed by generation of four regions of interest (ROI) for each cerebral hemisphere—frontal, temporal, parietal and occipital—and one for each cerebellar hemisphere in order to evaluate cortical perfusion asymmetry. The Asymmetry Index (AI) was calculated to provide a measurement of both magnitude and direction of perfusion asymmetry.ResultsAs assessed by visual examination, 99mTc-ECD cerebral distribution was irregular and patchy in HT patients, hypoperfusion being more frequently found in frontal lobes. AI revealed abnormalities in 12/16 HT patients, in three of the nine NTNG patients and in none of the normal controls. A significant difference in the mean AI was found between patients with HT and both patients with NTNG (p<0.003) and normal controls (p<0.001), when only frontal lobes were considered.ConclusionThese results show the high prevalence of brain perfusion abnormalities in euthyroid HT. These abnormalities are similar to those observed in cases of severe Hashimoto’s encephalopathy and may suggest a higher than expected involvement of CNS in thyroid autoimmune disease.

Bipolar disorders and Wilson’s disease

BackgroundThe aim of this study was to determine the risk for Bipolar Disorder (BD) in Wilson’s disease (WD) and to measure the impaired Quality of Life (QL) in BD with WD using standardized psychiatric diagnostic tools and a case control design.MethodsThis was a case control study. The cases were 23 consecutive patients with WD treated at the University Hospital in Cagliari, Italy, and the controls were 92 sex- and age-matched subjects with no diagnosis of WD who were randomly selected from a database used previously for an epidemiological study. Psychiatric diagnoses according to DSM-IV criteria were determined by physicians using structured interview tools (ANTAS-SCID). QL was measured by means of SF-12.ResultsCompared to controls, WD patients had lower scores on the SF-12 and higher lifetime prevalence of DSM-IV major depressive disorders (OR = 5.7, 95% CI 2.4–17.3) and bipolar disorders (OR = 12.9, 95% CI 3.6–46.3). BD was associated with lower SF-12 in WD patients.ConclusionsThis study was the first to show an association between BD and WD using standardized diagnostic tools and a case control design. Reports in the literature about increased schizophrenia-like psychosis in WD and a lack of association with bipolar disorders may thus have been based on a more inclusive diagnosis of schizophrenia in the past. Our findings may explain the frequent reports of loss of emotional control, hyperactivity, loss of sexual inhibition, and irritability in WD patients. This study was limited by a small sample size.

Thyroid diseases cause mismatch between MIBI scan and neck ultrasound in the diagnosis of hyperfunctioning parathyroids: usefulness of FNA–PTH assay

DESIGN To evaluate the efficacy of the main tools in the diagnostic localization of hyperfunctioning parathyroids (HP) in primary hyperparathyroidism (pHPT) with concomitant thyroid diseases. METHODS Forty-three patients with pHPT associated with nodular goiter (NG, n=32) and/or autoimmune thyroid diseases (AITDs, n=11) for a total of 63 neck lesions were considered. Sixteen patients displaying HP (16 lesions), unequivocally localized by sestaMIBI scintigraphy (MIBI) and neck ultrasound (US) (group I), were compared with 27 patients (47 neck lesions) displaying equivocal parathyroid localization (group II). In all cases, neck US, MIBI scan, cytology, and parathyroid hormone assay in fine-needle aspiration washout fluid (FNA-PTH) were performed. All patients finally underwent surgery. RESULTS According to histological examination, high FNA-PTH values (>103 pg/ml) correctly identified all HP in both groups of patients (100% of sensitivity and specificity). Both MIBI and US correctly identified all HP only in group I patients; in contrast, four patterns of mismatch between these techniques were observed in group II patients, leading to low diagnostic performances of neck US (71.4% sensitivity and 78.9% specificity) and of MIBI scan (35.7% sensitivity and 42.1% specificity). The latter was due to both false-negative (mainly in AITD) and false-positive (mainly in NG) scan images. CONCLUSIONS Coexistent thyroid diseases are responsible for mismatch between MIBI and US images resulting in equivocal HP localization. In these cases, FNA-PTH resulted in the most accurate tool to identify HP. However, although safe, it should be advised only to patients with uncertain HP localization.

A pattern of cerebral perfusion anomalies between Major Depressive Disorder and Hashimoto Thyroiditis

BackgroundThis study aims to evaluate relationship between three different clinical conditions: Major Depressive Disorders (MDD), Hashimoto Thyroiditis (HT) and reduction in regional Cerebral Blood Flow (rCBF) in order to explore the possibility that patients with HT and MDD have specific pattern(s) of cerebral perfusion.MethodsDesign: Analysis of data derived from two separate data banks.Sample: 54 subjects, 32 with HT (29 women, mean age 38.8 ± 13.9); 22 without HT (19 women, mean age 36.5 ± 12.25).Assessment: Psychiatric diagnosis was carried out by Simplified Composite International Diagnostic Interview (CIDIS) using DSM-IV categories; cerebral perfusion was measured by 99 mTc-ECD SPECT. Statistical analysis was done through logistic regression.ResultsMDD appears to be associated with left frontal hypoperfusion, left temporal hypoperfusion, diffuse hypoperfusion and parietal perfusion asymmetry. A statistically significant association between parietal perfusion asymmetry and MDD was found only in the HT group.ConclusionIn HT, MDD is characterized by a parietal flow asymmetry. However, the specificity of rCBF in MDD with HT should be confirmed in a control sample with consideration for other health conditions. Moreover, this should be investigated with a longitudinally designed study in order to determine a possible pathogenic cause. Future studies with a much larger sample size should clarify whether a particular perfusion pattern is associated with a specific course or symptom cluster of MDD.

Brain MRI and SPECT in the diagnosis of early neurological involvement in Wilson’s disease

PurposeTo evaluate the impact of brain MRI and single-photon emission computed tomography (SPECT) in early detection of central nervous system abnormalities in patients affected by Wilson’s disease (WD) with or without neurological involvement.MethodsOut of 25 consecutive WD patients, 13 showed hepatic involvement, ten hepatic and neurological manifestations, and twp hepatic, neurological, and psychiatric symptoms, including mainly movement disorders, major depression, and psychosis. Twenty-four healthy, age-gender matched subjects served as controls. All patients underwent brain MRI and 99mTc-ethyl-cysteinate dimer (ECD) SPECT before starting specific therapy. Voxel-by-voxel analyses were performed using statistical parametric mapping to compare differences in 99mTc-ECD brain uptake between the two groups.ResultsBrain MRI showed T2-weighted hyperintensities in seven patients (28%), six of whom were affected by hepatic and neurological forms. Brain perfusion SPECT showed pathological data in 19 patients (76%), revealing diffuse or focal hypoperfusion in superior frontal (Brodmann area (BA) 6), prefrontal (BA 9), parietal (BA 40), and occipital (BA 18, BA 39) cortices in temporal gyri (BA 37, BA 21) and in caudatus and putamen. Moreover, hepatic involvement was detected in nine subjects; eight presented both hepatic and neurological signs, while two exhibited WD-correlated hepatic, neurological, and psychiatric alterations. All but one patient with abnormal MRI matched with abnormal ECD SPECT. Pathologic MRI findings were obtained in six out of ten patients with hepatic and neurological involvement while abnormal ECD SPECT was revealed in eight patients. Both patients with hepatic, neurological, and psychiatric involvement displayed abnormal ECD SPECT and one displayed an altered MRI.DiscussionThese findings suggest that ECD SPECT might be useful in detecting early brain damage in WD, not only in the perspective of assessing and treating motor impairment but also in evaluating better the less investigated disorders in the cognitive domain.