Systematic Review of the First 40 Cases of 177Lu-PSMA Therapy in the Treatment of Non-prostatic Cancer.

BACKGROUND/AIM: The current systematic review aimed to collect and analyze all available published and unpublished cases in which prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (177Lu-PSMA) was used to treat non-prostatic cancer. MATERIALS AND METHODS: Literature search and evidence acquisition through contacts with organizations that use 177Lu-PSMA were employed. PubMed/Medline, SCOPUS, and ScienceDirect searches were performed following PRISMA recommendations. The search strategy was to screen all articles describing 177Lu-PSMA radioligand therapy published to date with the key word "177Lu-PSMA". These articles were collected and screened for non-prostatic cancer cases. Quality assessment was performed using the GRADE criteria. RESULTS: A total of 713 articles were screened, and the search revealed 15 eligible records. Forty patients with a mean age of 51.2±18.5 years were treated with 177Lu-PSMA for non-prostatic cancer. Of them, 30 cases were published, and 10 were found in medical institution records. Cancers of the salivary glands were most often targeted (13/40), followed by various brain cancer types (8/40), and osteosarcoma (6/40). The authors used previously established protocols for castration-resistant prostate cancer with the dose per cycle as 6.0-7.4 GBq and the number of cycles between one and four. Toxicity was estimated as low, and 21 out of 28 patients with reported outcomes survived to the time of the publication. CONCLUSION: PSMA-targeted radioligand therapy was infrequently used to treat different non-prostatic cancer types in various target organs. These pioneering efforts indicate that 177Lu-PSMA can be used to treat non-prostatic cancer with PSMA expression. The toxicity of such treatment was low, and the outcome was relatively good.

Nuclear imaging in Parkinson's disease: The past, the present, and the future.

The current review analyzed Parkinson's disease-related (PD) literature published from 1817 to 2021 and specifically concentrated on imaging-related works published from the 1960s to 2021. We analyzed the history of PD-related imaging development, its current condition, and pointed out some understudied aspects to be investigated in the future. The present review is specifically concentrated on nuclear imaging techniques. The available imaging armamentarium for PD investigation is very broad, variable, and diversified and includes structural, diffusion-weighted and diffusion tensor, resting-state, and task-based functional MRI, proton magnetic resonance spectroscopy, transcranial B-mode sonography, single-photon emission CT (SPECT), and positron emission tomography (PET). Specifically, PET is a reliable tool for quantifying nigrostriatal functions, glucose metabolism, amyloid, tau, and α-synuclein molecular imaging, as well as neuroinflammation. Besides 18F-DOPA and 18F-FDG, PET and SPECT use various other radiopharmaceuticals. Also, some studies have demonstrated that myocardial 123I-MIBG scintigraphy can be useful for the early differential diagnosis of patients with PD from other atypical PD. However, in addition to further perfecting of differential diagnosis imaging tools, some aspects of etiology (PD genetics), pathology (the pons and medulla), pathophysiology (neuroinflammation), and early diagnosis of PD remain understudied. The currently available set of neuroimaging tools can provide adequate imaging data for early diagnosis, differential diagnosis, progression assessment, and treatment assessment of PD. To adjust this armamentarium to routine clinical needs, there is an urgent need for the generally accepted protocol for PD-related imaging investigations. Closer cooperation and data exchange between radiologists and pathologists are desirable.

Pressure pulsations enhance penetration index in COPD.

This study was done in order to evaluate the effect of a novel pressure pulsation device (Pulsehaler™, Respinova Ltd., Israel) on the deposition pattern of inhaled aerosol in the lungs of COPD patients. Fifteen COPD patients were recruited to undergo spirometry and SPECT-CT lung scan following nebulization of radioactively labeled albuterol in saline solution with a jet nebulizer ("NEB") and with a combined Pulsehaler™/jet nebulizer ("PH + NEB") treatment. Central and peripheral segments of the coronal and transverse SPECT scans were evaluated for total counts and for the ratios between peripheral counts and central counts (penetration Index, "PI"). There was a significant improvement in FEV1 from before to after albuterol treatment in the PH + NEB group (151 ml ± 187, p < 0.008), but not in the NEB only group (66 ml ± 125, p = 0.06). FVC, FEF25-75, FEV1%, FVC%, FEF25, FEF50, and FEF75 also improved significantly in the PH + NEB group but not the NEB group. There were significant improvements seen between treatments for FEF25-75 (PH + NEB > NEB, p = 0.0176), FEF75 (PH + NEB > NEB, p = 0.0028), but not for the other spirometry measures. Borg scores also were improved significantly improved in PH + NEB vs NEB (p = 0.0006). Total lung deposition and total body deposition were lower in the PH + NEB treatments vs the NEB treatments. However, PI values were 3.08 ± 0.67 times greater on average with the PH + NEB (p = 0.026) as compared to NEB only. The magnitude of the increased penetration index observed in this study indicates that pressure pulsations should be further explored as means to improve drug delivery into the distal small airways of the bronchial tree. Effects of the pressure pulsations on small airway patency could be the mechanism by which the effect was achieved.

Enhancing capacity and synthesis of [68Ga]68-Ga-PSMA-HBED-CC with the lyophilized ready-to-use kit for nuclear pharmacy applications.

INTRODUCTION: The authors describe the newly proposed synthesis technique for the gallium-68 (Ga-68)-labeled tracer ([Ga]Ga-PSMA-HBED-CC) for imaging expression of the prostate-specific membrane antigen (PSMA). An effort was applied to design the lyophilized cold kit (isoPROtrace-11) as a time-saving technique resulting in increased radiochemical yields. PROCEDURES: The initial material for labeling was obtained from a Ge/Ga-generator. For labeling with the lyophilized cold kit isoPROtrace-11, 2.5 ml 0.1 M HCl of the middle Ga-68 elution fraction were added to the kit, shook for dissolving the vial's contents and kept for 5 minutes at room temperature. A systematic comparison was carried out between results obtained with the cold kit technique and with previously used Modular-Lab module concerning the radiochemical yield, purity, and the time of producing. RESULTS: Automated module-involved synthesis of [Ga]Ga-PSMA-HBED- CC resulted in a radiochemical yield of 84.2 ± 6.3% and purity of >95% after 25 minutes. The room temperature cold kit gave a radiochemical yield of >98% and purity of >95% after 5 minutes. CONCLUSION: Using the kit method reduced the labeling time. The cold kit method increased production efficiency because less of the eluted Ga-68 was wasted.

Imaging-based predictors for hyperbaric oxygen therapy outcome in post-stroke patients. Report 1.

We tested the hypothesis that if SPECT/CT-detected volumes of active and inactive parts of brain tissue present correlation with the results of hyperbaric oxygen therapy (HBOT) of ischemic stroke, SPECT imaging may serve as a selective tool for post-stroke patients to indicate cases that may significantly benefit from HBOT. A retrospective analysis was conducted on 62 consecutive patients administered for HBOT after the ischemic stroke episode. All patients received 60 daily hyperbaric sessions consisting of 90 min of exposure to 100% oxygen at a pressure of 0.2 MPa. The results of the treatment were assessed in correlation with SPECT/CT-detected changes of volumes of the penumbra area around the stroke zone. Patients who significantly benefitted from HBOT (n = 24) by an improvement of their clinical neurologic status and quality of life had the large penumbra zone (363 ± 20.5 ml) that was significantly diminished during HBOT. Patients who did not benefit from HBOT (n = 20) had a relatively small volume of the penumbra zone (148 ± 29.3 ml) and its further diminishing during HBOT was insignificant. The HBOT results were unclear in 18 patients with penumbra volumes between these values. These findings support our hypothesis that the large volume of the penumbra area around the stroke zone can serve as a significant predictor for positive clinical outcome following HBOT in post-stroke patients. The SPECT/CT-based assessment procedure of the volume of the penumbra may serve as an effective selecting tool when HBOT is administered for patients with ischemic stroke.

Calf "Arch Sign" Seen on a Tc-99m-MDP Bone Scan Is Indicative of Synovial Fluid Leak in Ruptured Baker's Cysts: Case Reports and Analysis of Literature.

The authors present two cases in which the ruptured popliteal (Baker's) cysts remained undetected and were diagnosed only during an isotope investigation. The aim was to describe a specific imaging sign, the "arch sign", that is indicative of ruptured Baker's cysts. In both cases, the whole-body imaging was performed 2 hours after injection of 706.7 MBq of Tc-99m-MDP. Single-photon emission computed tomography (SPECT) imaging was performed to localize an accumulation of the radiopharmaceutical. An analysis of literature was performed to connect these cases with previously reported data and to detect the pathognomonic radio image sign of ruptured popliteal cysts. The arch-shaped distribution of the radiopharmaceutical below the knee joints was seen already on the whole-body bone scan image in both cases. An anterior view of SPECT MIP images showed the arched accumulation of the Tc-99m-MDP bone tracer along the postero-medial aspect of the right calf secondary to synovial fluid leak from a ruptured Baker's cyst. The similar arthroscintigrams were published since 1971 without recognizing this sign as pathognomonic. Tc-99m-MDP bone scanning is sensitive for a Baker's cyst with synovial effusion, and distribution of a radiopharmaceutical in the medial posterior calf in a shape of an arch, the arch sign, may serve as an indicator of a ruptured popliteal cyst.

Low-radiation of technetium-99m-sestamibi and single-photon emission computed tomography/computed tomography to diagnose parathyroid lesions.

We compared preoperative regular activity and low-activity radiology-based predictions with real surgical and pathological findings for parathyroidectomy surgery. The study retrospectively analyzed 54 consecutive cases (2009-2016) for benign tumor removal. Technetium-99m (Tc-99m)-sestamibi was used as a diagnostic radiopharmaceutical for diagnostic dual-phase parathyroid scintigraphy and single-photon emission computed tomography/computed tomography. We assessed images obtained with the radiation activity of 925 megabecquerel (MBq) and images obtained with the activity of 185 MBq. The study compared preoperative evaluation of tumor presence, multiplicity, location, and the type of pathology with actual data that were revealed during the operation and pathological investigation. The agreement between preoperative radiological prediction and actual location, number, and type of the parathyroid lesions was achieved in 98.4% (n = 61/62 lesions). The agreement between 925 MBq-based and 185-MBq based investigations was 100%. The agreement between radiological and pathological findings was 100% for both investigations. Our data suggest that the radioactivity of 185 MBq applied in the evaluation of the parathyroid glands provides results similar to the currently used 925-1110 MBq if used for diagnostic dual-phase parathyroid scintigraphy with Tc-99m-sestamibi. Such radioactivity may reduce the exposure to radiation of the patients and the staff without compromising results of the investigation.

Free craniotomy versus osteoplastic craniotomy, assessment of flap viability using 99mTC MDP SPECT.

There are currently two accepted neurosurgical methods to perform a bony flap. In an osteoplastic flap, the flap is attached to surrounding muscle. In a free flap, the flap is not attached to adjacent tissues. The former is less common due to its complexity and the extensive time required for the surgery; yet the rate of infection is significantly lower, a clear explanation for which is unknown. The objective of this study was to test the hypothesis that the osteoplastic flap acts as a live implant that resumes its blood flow and metabolic activity; contrasting with the free flap, which does not have sufficient blood flow, and therefore acts as a foreign body. Seven patients who underwent craniotomy with osteoplastic flaps and five with free flaps had planar bone and single photon emission computed tomography (SPECT) scans of the skull at 3-7days postoperative, after injection of the radioisotope, 99m-technetium-methylene diphosphonate (99m-Tc-MDP). We compared radioactive uptake as a measure of metabolic activity between osteoplastic and free flaps. Mean normalized radioactive uptakes in the centers of the flaps, calculated as the ratios of uptakes in the flap centers to uptakes in normal contralateral bone, were [mean: 1.7 (SD: 0.8)] and [0.6 (0.1)] for the osteoplastic and free flap groups respectively and were [2.4 (0.8)] and [1.3 (0.4)] in the borders of the flaps. Our analyses suggest that in craniotomy, the use of an osteoplastic flap, in contrast to free flap, retains bone viability.

Hyperbaric oxygen therapy can diminish fibromyalgia syndrome--prospective clinical trial.

BACKGROUND: Fibromyalgia Syndrome (FMS) is a persistent and debilitating disorder estimated to impair the quality of life of 2-4% of the population, with 9:1 female-to-male incidence ratio. FMS is an important representative example of central nervous system sensitization and is associated with abnormal brain activity. Key symptoms include chronic widespread pain, allodynia and diffuse tenderness, along with fatigue and sleep disturbance. The syndrome is still elusive and refractory. The goal of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on symptoms and brain activity in FMS. METHODS AND FINDINGS: A prospective, active control, crossover clinical trial. Patients were randomly assigned to treated and crossover groups: The treated group patients were evaluated at baseline and after HBOT. Patients in the crossover-control group were evaluated three times: baseline, after a control period of no treatment, and after HBOT. Evaluations consisted of physical examination, including tender point count and pain threshold, extensive evaluation of quality of life, and single photon emission computed tomography (SPECT) imaging for evaluation of brain activity. The HBOT protocol comprised 40 sessions, 5 days/week, 90 minutes, 100% oxygen at 2ATA. Sixty female patients were included, aged 21-67 years and diagnosed with FMS at least 2 years earlier. HBOT in both groups led to significant amelioration of all FMS symptoms, with significant improvement in life quality. Analysis of SPECT imaging revealed rectification of the abnormal brain activity: decrease of the hyperactivity mainly in the posterior region and elevation of the reduced activity mainly in frontal areas. No improvement in any of the parameters was observed following the control period. CONCLUSIONS: The study provides evidence that HBOT can improve the symptoms and life quality of FMS patients. Moreover, it shows that HBOT can induce neuroplasticity and significantly rectify abnormal brain activity in pain related areas of FMS patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01827683.

Improvement of memory impairments in poststroke patients by hyperbaric oxygen therapy.

OBJECTIVE: Several recent studies have shown that hyperbaric oxygen (HBO2) therapy carry cognitive and motor therapeutic effects for patients with acquired brain injuries. The goal of this study was to address the specific effects of HBO2 on memory impairments after stroke at late chronic stages. METHOD: A retrospective analysis was conducted on data of 91 stroke patients 18 years or older (mean age ∼60 years) who had either ischemic or hemorrhagic stroke 3-180 months before HBO2 therapy (M = 30-35 months). The HBO2 protocol included 40 to 60 daily sessions, 5 days per week, 90 min each, 100% oxygen at 2ATA, and memory tests were administered before and after HBO2 therapy using NeuroTrax's computerized testing battery. Assessments were based on verbal or nonverbal, immediate or delayed memory measures. The cognitive tests were compared with changes in the brain metabolic state measured by single-photon emission computed tomography. RESULTS: Results revealed statistically significant improvements (p < .0005, effect sizes medium to large) in all memory measures after HBO2 treatments. The clinical improvements were well correlated with improvement in brain metabolism, mainly in temporal areas. CONCLUSIONS: Although further research is needed, the results illustrate the potential of HBO2 for improving memory impairments in poststroke patients, even years after the acute event.

Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury - randomized prospective trial.

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of death and disability in the US. Approximately 70-90% of the TBI cases are classified as mild, and up to 25% of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging. The current study tested the effectiveness of Hyperbaric Oxygen Therapy (HBOT) in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments. METHODS AND FINDINGS: The trial population included 56 mTBI patients 1-5 years after injury with prolonged post-concussion syndrome (PCS). The HBOT effect was evaluated by means of prospective, randomized, crossover controlled trial: the patients were randomly assigned to treated or crossover groups. Patients in the treated group were evaluated at baseline and following 40 HBOT sessions; patients in the crossover group were evaluated three times: at baseline, following a 2-month control period of no treatment, and following subsequent 2-months of 40 HBOT sessions. The HBOT protocol included 40 treatment sessions (5 days/week), 60 minutes each, with 100% oxygen at 1.5 ATA. "Mindstreams" was used for cognitive evaluations, quality of life (QOL) was evaluated by the EQ-5D, and changes in brain activity were assessed by SPECT imaging. Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period. SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements. CONCLUSIONS: HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage. TRIAL REGISTRATION: ClinicalTrials.gov NCT00715052.

Hyperbaric oxygen induces late neuroplasticity in post stroke patients--randomized, prospective trial.

BACKGROUND: Recovery after stroke correlates with non-active (stunned) brain regions, which may persist for years. The current study aimed to evaluate whether increasing the level of dissolved oxygen by Hyperbaric Oxygen Therapy (HBOT) could activate neuroplasticity in patients with chronic neurologic deficiencies due to stroke. METHODS AND FINDINGS: A prospective, randomized, controlled trial including 74 patients (15 were excluded). All participants suffered a stroke 6-36 months prior to inclusion and had at least one motor dysfunction. After inclusion, patients were randomly assigned to "treated" or "cross" groups. Brain activity was assessed by SPECT imaging; neurologic functions were evaluated by NIHSS, ADL, and life quality. Patients in the treated group were evaluated twice: at baseline and after 40 HBOT sessions. Patients in the cross group were evaluated three times: at baseline, after a 2-month control period of no treatment, and after subsequent 2-months of 40 HBOT sessions. HBOT protocol: Two months of 40 sessions (5 days/week), 90 minutes each, 100% oxygen at 2 ATA. We found that the neurological functions and life quality of all patients in both groups were significantly improved following the HBOT sessions while no improvement was found during the control period of the patients in the cross group. Results of SPECT imaging were well correlated with clinical improvement. Elevated brain activity was detected mostly in regions of live cells (as confirmed by CT) with low activity (based on SPECT) - regions of noticeable discrepancy between anatomy and physiology. CONCLUSIONS: The results indicate that HBOT can lead to significant neurological improvements in post stroke patients even at chronic late stages. The observed clinical improvements imply that neuroplasticity can still be activated long after damage onset in regions where there is a brain SPECT/CT (anatomy/physiology) mismatch.

Disseminated dermatophytic pseudomycetoma caused by Microsporum species.

BACKGROUND: Dermatophyte infection is almost exclusively a superficial cutaneous mycosis usually confined to the stratum corneum of nails and hairs of normal hosts. Deep cutaneous and subcutaneous infections due to dermatophytes are exceedingly rare and usually limited to immunosuppressed individuals. These infections remain chronic and persist in spite of treatment. MATERIALS AND METHODS: We report two clinical cases of disseminated dermatophytic pseudomycetoma caused by Microsporum gypseum and Microsporum canis in immunosuppressed patients. RESULTS: Patient 1, in 2008, showed improvement with fluconazole, cephalothin, and terbinafine treatment for Microsporum gypseum. After suspension of the treatment, new lesions appeared and culture from material was positive. In 2009, she presented confluent papules and nodules forming plaques on her face and neck with the isolation of Microsporum canis. Clinical response to this treatment was poor. Patient 2 was affected by both tinea corporis due to Trichophyton rubrum and dermatophytic pseudomycetoma caused by Microsporum canis. The response to treatment was successful with oral itraconazole and local surgical excision. CONCLUSIONS: It is important to recognize these atypical presentations of dermatophytic infections in immunosuppressed patients, which may warrant a more aggressive treatment in order to achieve resolution.

99m Tc-albumin nanocolloid joint scintigraphy in rheumatoid arthritis patients who are in clinical remission - is remission real ?

OBJECTIVES: To make a comparison between the clinical data and the imaging results with 99mTc-nanocolloid scintigraphy in rheumatoid arthritis (RA) patients considered to be in remission. METHODS: Forty RA patients found to be in clinical remission according to the ACR and the EULAR (DAS28<2.6) criteria were studied. The group included 29 females and 11 males with a mean age of 60.8+/-13.5 years (range 22-86) and a mean disease duration of 13.4+/-7.7 years (range 2-23). The mean time of remission in the study group was 22.2+/-5.2 months (range 11-36). Each patient was given an intravenous injection of 555MBq of 99mTc-nanocalloid (NC). Spot views of the skeleton were taken and a SPECT-CT was done on the wrists and hands. A scan was considered positive when at least one of the hand joints showed increased tracer uptake. RESULTS: The 99mTc-nanocalloid scintigraphy was negative in 14 (35%) and positive for active joint disease in 26 (65%) patients. Twenty four out of the 26 patients with positive scan (92%) were sero-positive while those who had a negative scintigraphy were all sero-negative except one. No correlation was found between the type of treatment used, the time that elapsed from remission, or laboratory parameters (ESR CRP) and the scintigraphic results. CONCLUSIONS: The clinical criteria used for remission in RA are not consistent with the actual inflammatory activity in the joints. These results are especially emphasised in the subgroup of sero-positive patients.

Clinical characteristics and long-term mortality of occult hip fracture elderly patients.

BACKGROUND AND OBJECTIVE: Occult hip fractures (OHF) occur in a minute population of patients. Diagnosis is made via magnetic resonance imaging (MRI) or alternatively via bone scan. Very little is known about the clinical characteristics of OHF patients. Our aim was to characterize the clinical and long-term survival of OHF in elderly patients and to determine if a certain subgroup of patients would benefit from an MRI investigation following normal or equivocal radiography. METHODS: Twenty-nine OHF patients diagnosed by a bone scan during 1995-2004 were compared with a control group of 94 randomly chosen hip fractured patients diagnosed by plain radiography in the same hospital and during the same period. RESULTS: Mean age, women/men ratio, place of residence, comorbidities, cognitive and functional status were similar in the OHF and control group. Twenty-two (75.9%) and 4 (13.8%) patients in the OHF group had had subcapital and intertrochanteric fractures respectively, vs. 41 (43.6%) and 47 (50%) in the control group (p=0.003). Diagnosis delay in the OHF group was 16.8+/-26.5 days vs. 2.5+/-2.9 days (p<0.001) in the control group. There were fewer operations and complications in the OHF group compared to the control group (p<0.001 and p=0.017, respectively). During a 13-year follow-up, no differences in survival were found between the two groups nor any differences between those operated on and those who were not. CONCLUSIONS: OHF patients have no distinctive clinical characteristics or long-term survival. The delay in diagnosing OHF is too much long and is probably related to the high prevalence of conservative treatment. MRI investigation is recommended whenever OHF are suspected and surgical treatment is considered, in order to improve diagnosis and treatment.

Brain mapping of patients with lung cancer and controls: inquiry into tumor-to-brain communication.

UNLABELLED: Recent converging evidence suggests that the brain may receive stimuli and possibly modulate tumor progression via the vagus nerve. The present study aimed to compare brain metabolism in patients with and without lung cancer and to assess if significant differences exist in regions associated with the vagus nerve. METHODS: Eighteen patients with lung malignancy and 19 controls underwent (18)F-FDG PET of the brain. Brain metabolism was compared using statistical parametric mapping. RESULTS: Patients with lung malignancy showed a statistically significantly higher right cerebellar metabolism. CONCLUSION: This finding may be related to the role of the cerebellum in immune regulation, because of its proximity to the nucleus tractus solitarius innervated by the vagus and its connections with the hypothalamus. This higher metabolism in the right cerebellum may reflect an attempt to reinstate homeostasis in functions such as respiration and immunity pertinent to lung malignancy.

Unilateral spiny hyperkeratosis: case report and review of the literature.

We describe the first case of unilateral spiny hyperkeratosis (SH) of the left hand, review the literature and discuss possible patho- mechanisms. SH can be sporadic or familial, often appearing in healthy individuals. However, there is an association with various malignancies in a significant number of the sporadic cases. Although there is no satisfactory explanation of this association, we agree with previous authors that a patient with SH appearing in adult life should be evaluated and followed for the presence of malignancy. Other patients with SH may suffer from a variety of nonmalignant diseases, which may be coincidental or causally related. SH is not a premalignant lesion of the skin and should not be confused with porokeratosis which has a malignant potential. Except for excision of individual lesions, there is no permanent cure.

[Nuclear neuroimaging of dopamine transporter in Parkinsonism--role in routine clinical practice].

Idiopathic Parkinson's disease (IPD) is a neurodegenerative condition characterized pathologically by the degeneration of dopaminergic neuron in the substantia nigra and production of intracytoplasmic inclusion bodies (Lewy body) in the retained neurons. Clinically, the disease is characterized by the presence of tremor, rigidity and bradykinesia. These clinical features also occur in other neurodegenerative diseases and by dopamine receptor antagonist drugs. Brain SPECT imaging of the dopamine transporter (DAT) with specific radioligands is a sensitive method for examining the integrity of the presynaptic dopaminergic system. However, with this main clinical application it is hard to diagnose patients with mild, incomplete, or uncertain Parkinsonism. The ligands belong to a group of compounds derived from cocaine that bind to the dopamine transporter and include â-CIT, IPT, TRODAT-1, FP-CIT tagged with either Iod-123 or Technetium-99m radioisotopes. DAT imaging is abnormal even in the earliest clinical presentation of IPD but a normal scan suggests an alternative diagnosis such as essential tremor, vascular Parkinsonism, drug-induced Parkinsonism, or psychogenic Parkinsonism.

Hypoparathyroidism, retardation, and dysmorphism syndrome: impaired early growth and increased susceptibility to severe infections due to hyposplenism and impaired polymorphonuclear cell functions.

Hypoparathyroidism, retardation, and dysmorphism (HRD) syndrome is the first reported disease caused by a defect in the tubulin folding and assembly pathway. We aimed to summarize our experience with a cohort of patients with HRD, analyze their growth, and evaluate patients' polymorphonuclear cell (PMN) functions. The records of 22 HRD patients in a single medical center were reviewed. Growth during infancy and early childhood were analyzed by the Infancy-Childhood-Puberty (ICP) growth model. PMN functions were compared with healthy controls. Twelve patients died and many hospitalizations due to infections and convulsions were recorded. Growth measurements, expressed as weight and height SD scores in boys at a mean age of 4 y were -13.1+/-3.8 and -8.7+/-1 and -16.6+/-4.4 and -9.5+/-2.4, respectively, in girls at a mean age of 6.4 y. Chemotactic migration, random migration, and phagocytosis of PMN from HRD patients were significantly lower than that of PMN from healthy controls. No significant differences were found in superoxide production of PMN from patients compared with controls. Functional hyposplenism has been demonstrated in most of the studied patients. The defect in the tubulin folding and assembly pathway, previously described in HRD, has grave consequences on growth and PMN functions.