Brain Scintigraphy Research Articles

Duropathy as a rare motor neuron disease mimic: from bibrachial amyotrophy to infratentorial superficial siderosis

BackgroundBibrachial amyotrophy associated with an extradural CSF collection and infratentorial superficial siderosis (SS) are rare conditions that may occasionally mimic ALS. Both disorders are assumed to be due to dural tears.Case presentationA 53-year-old man presented with a 7-year history of slowly progressive asymmetric bibrachial amyotrophy. Initially, a diagnosis of atypical motor neuron disease (MND) was made. At re-evaluation 11 years later, upper limb wasting and weakness had further progressed and were accompanied by sensorineural hearing loss. MRI of the brain and spine demonstrated extensive supra- and infratentorial SS (including the surface of the whole spinal cord) as well as a ventral longitudinal intraspinal fluid collection (VLISFC) extending along almost the entire thoracic spine. Osteodegenerative changes were observed at C5-C7 level, with osteophytes protruding posteriorly. The bony spurs at C6-C7 level were hypothesized to have lesioned the dura, causing a CSF leak and thus a VLISFC. Review of the MRI acquired at first evaluation showed that the VLISFC was already present at that time (actually beginning at C7 level), whereas the SS was not. 19 years after the onset of upper limb weakness, the patient additionally developed parkinsonism. Response to levodopa, brain scintigraphy with 123I-ioflupane and brain MRI with nigrosome 1 evaluation were consistent with idiopathic Parkinson’s disease (PD). On the latest follow-up 21 years after symptom onset, the VLISFC was unchanged, as were upper arm weakness and wasting.ConclusionsBased on the long-term follow-up, we could establish that, while the evidence of the VLISFC was concomitant with the clinical presentation of upper limb amyotrophy and weakness, the radiological signs of SS appeared later. This suggests that SS was not per se the cause of the ALS-like clinical picture, but rather a long-term sequela of a dural leak. The latter was instead the causative lesion, giving rise to a VLISFC which compressed the cervical motor roots. Dural tears can actually cause several symptoms, and further studies are needed to elucidate the pathophysiological correlates of “duropathies”. Finally, as iron metabolism has been implicated in PD, the co-occurrence of PD with SS deserves further investigation.

Single-Photon Emission Computed Tomography in the Diagnosis of Early Postoperative Cognitive Dysfunction After Combined Carotid Endarterectomy and Coronary Artery Bypass Grafting

Objective: to study the contribution of regional cerebral blood flow (rCBF) indicators to the diagnosis of early postoperative cognitive dysfunction (POCD) in patients with multifocal atherosclerosis (MFA) with heart and brain revascularization.Material and methods. The study involved 45 patients with MFA of coronary and precerebral arteries. We analyzed patients’ cognitive indicators and conducted brain scintigraphy before and after revascularization. The criteria for inclusion in the study were: scheduled combined revascularization of coronary and precerebral arteries; signed informed consent to participate in the study. Criteria for exclusion were: refusal to participate in the study, diseases that would prevent examination. The study of cognitive functions was performed using flow was assessed by single-photon emission computed tomography using lipophilic radiopharmaceutical 99mTc-HMPAO “Ceretec”.Results. The frequency of early POCD in the isolated coronary artery bypass grafting (CABG) group was 73.3%, in the combined carotid endarterectomy (СEA) and CABG group it was 72.5% (p ˃ 0.05). The rCBF index in the isolated CABG group compared with the combined СEA and CABG group was higher in the right and left temporal lobes (p = 0.01 and p = 0.04), in the right frontal lobe (p = 0.03), right parietal lobe (p = 0.005), and in the right and left occipital lobes (p = 0.03 and p = 0.03). In the postoperative period, in the isolated CABG group, right parietal lobe perfusion (p = 0.01), and right and left occipital lobe perfusion (p = 0.01 and p = 0.01) decreased compared to the baseline values. In the combined СEA and CABG group, in the early postoperative period, cerebral perfusion did not change significantly. Right parietal lobe perfusion was higher in the isolated CABG group compared with the combined CABG and СEA group (p = 0.04). The greatest contribution to the development of early POCD in patients after isolated CABG was made by the left temporal lobe perfusion (p = 0.025), in patients after combined CABG and СEA – by the right parietal lobe perfusion (p = 0.04) in the early postoperative period.Conclusion. Assessment of cerebral perfusion in patients before and after surgery can be used to identify areas affected during surgery, as a method for monitoring the safety of procedure, and as an assessment of the preventive methods against POCD.

Brain Failure and Brain Death

Brain failure consists of a wide spectrum of central nervous system pathologies with many different neurologic manifestations. The causes of brain failure include several disease processes that result in decreased supply of blood and oxygen to the brain or metabolic derangements that affect the central nervous system. Brain failure usually results in some altered level of consciousness. Brain failure and brain death result in several pathophysiologic changes. The definition of brain death is controversial and evolving. However, clear guidelines to determine brain death have been established. These guidelines state that three cardinal findings be present to establish brain death: (1) coma or unresponsiveness, (2) absence of brainstem reflexes, and (3) apnea. Several clinical parameters must be met when these findings are made. Adjunctive studies such as four-vessel cerebral angiography, electroencephalography, and nuclear brain scintigraphy can help make a diagnosis of brain death. When brain death is established, suitability for organ transplantation should be evaluated. After obtaining consent, potential organ donation should be optimized for possible donation. This review contains 2 figures, 3 tables, and 69 references. Key Words: brain failure, brain death, consciousness, coma, death, delirium, organ donation

Brain Failure and Brain Death

Brain failure consists of a wide spectrum of central nervous system pathologies with many different neurologic manifestations. The causes of brain failure include several disease processes that result in decreased supply of blood and oxygen to the brain or metabolic derangements that affect the central nervous system. Brain failure usually results in some altered level of consciousness. Brain failure and brain death result in several pathophysiologic changes. The definition of brain death is controversial and evolving. However, clear guidelines to determine brain death have been established. These guidelines state that three cardinal findings be present to establish brain death: (1) coma or unresponsiveness, (2) absence of brainstem reflexes, and (3) apnea. Several clinical parameters must be met when these findings are made. Adjunctive studies such as four-vessel cerebral angiography, electroencephalography, and nuclear brain scintigraphy can help make a diagnosis of brain death. When brain death is established, suitability for organ transplantation should be evaluated. After obtaining consent, potential organ donation should be optimized for possible donation. This review contains 2 figures, 3 tables, and 69 references. Key Words: brain failure, brain death, consciousness, coma, death, delirium, organ donation

Brain Failure and Brain Death

Brain failure consists of a wide spectrum of central nervous system pathologies with many different neurologic manifestations. The causes of brain failure include several disease processes that result in decreased supply of blood and oxygen to the brain or metabolic derangements that affect the central nervous system. Brain failure usually results in some altered level of consciousness. Brain failure and brain death result in several pathophysiologic changes. The definition of brain death is controversial and evolving. However, clear guidelines to determine brain death have been established. These guidelines state that three cardinal findings be present to establish brain death: (1) coma or unresponsiveness, (2) absence of brainstem reflexes, and (3) apnea. Several clinical parameters must be met when these findings are made. Adjunctive studies such as four-vessel cerebral angiography, electroencephalography, and nuclear brain scintigraphy can help make a diagnosis of brain death. When brain death is established, suitability for organ transplantation should be evaluated. After obtaining consent, potential organ donation should be optimized for possible donation. This review contains 2 figures, 3 tables, and 69 references. Key Words: brain failure, brain death, consciousness, coma, death, delirium, organ donation

Brain Failure and Brain Death

Brain failure consists of a wide spectrum of central nervous system pathologies with many different neurologic manifestations. The causes of brain failure include several disease processes that result in decreased supply of blood and oxygen to the brain or metabolic derangements that affect the central nervous system. Brain failure usually results in some altered level of consciousness. Brain failure and brain death result in several pathophysiologic changes. The definition of brain death is controversial and evolving. However, clear guidelines to determine brain death have been established. These guidelines state that three cardinal findings be present to establish brain death: (1) coma or unresponsiveness, (2) absence of brainstem reflexes, and (3) apnea. Several clinical parameters must be met when these findings are made. Adjunctive studies such as four-vessel cerebral angiography, electroencephalography, and nuclear brain scintigraphy can help make a diagnosis of brain death. When brain death is established, suitability for organ transplantation should be evaluated. After obtaining consent, potential organ donation should be optimized for possible donation. This review contains 2 figures, 3 tables, and 69 references. Key Words: brain failure, brain death, consciousness, coma, death, delirium, organ donation

Assessment of informative value of effective cerebral blood flow calculation technique according to 99mTc-HMPAO polyphase scintigraphy data

Background. According to single-photon emission computed tomography (SPECT) data, the most common technique to calculate volume cerebral blood flow (VCBF) is N.A. Lassen method. Following it, VCBF in different segments of the brain is assessed in comparison with blood flow in the cerebellum, where it is considered to be constant. However, this approach does not take into account that in some pathologies, in particular, injuries, occlusions of blood vessels, VCBF of the cerebellum also does change. Therefore, an original technique of calculating regional VCBF based on polyphase scintigraphy has been developed, which will make it possible to make a more accurate assessment of the effective perfusion of the brain.
 Purpose – to evaluate the clinical informative value of the developed technique for calculating effective cerebral blood flow according to 99mTc-HMPAO (hexamethylpropyleneaminoxime) polyphase brain scintigraphy data.
 Materials and methods. The study is focused on analyzing two groups of patients: Group A represented by patients with signs of chronic cerebral ischemia and Group B enrolling patients in the interim and long term of explosive minor brain injury (n=22). Group A patients were divided into two subgroups, depending on the presence of structural and hemodynamic changes in the vertebral arteries (VA) according to ultrasound (US) of the major vessels of the brain. I-A subgroup (n=13) was made up by those patients who had structural lesions of the vertebrobasilar basin; II-A (n=27) patients had no relevant signs.
 All patients underwent a comprehensive clinical examination including neuropsychological testing, ultrasound of major vessels, magnetic resonance imaging, single-photon emission computed tomography (SPECT). Effective volume cerebral blood flow (VCBF), according to the SPECT data, was calculated based on the original technique (VCBFSB). VCBFSB values were compared with the SPECT data using N.A. Lassen (VCBFLassen) method and the ultrasound data.
 Results and discussion. Analysing the data of the groups of patients with hemodynamic impairment in the vertebro-basilar basin shows that, according to the scintigraphy of VCBF, I-A group patients differ from II-A group on average 1.82± 0.06 times the amount for CBFSB and 0.95± 0.04 for CBFLassen. The total mean blood flow in the carotid and vertebral arteries of I-A group patients was 748.19±198.42 mL/min, II-A group patients – 1112.23±63.71 mL/min. Comparing the mean values of the hemodynamic parameters of the brain of Group B patients with the data of Group II-A
 patients, VCBFSB was 1.33±0.25-fold decreased, while CBFLassen showed 1.03±0.14-fold decrease of perfusion (in total average blood flow of vertebral and carotid arteries according to US of Group B – 1760±580 ml/min).
 Conclusions. Preliminary clinical studies, using the developed technique for calculating volume cerebral blood flow according to 99mTc-HMPAO scintigraphy data with the corresponding software, showed a rather high sensitivity in assessing VCBF in case of pathological changes in the brain, especially, in occlusion of the major vessels of the brain and contusions resulting from battle trauma, whereas N.A. Lassen method was insufficiently informative. The regression analysis of US data, SPECT data and neuropsychological testing shows clear linear correlation relationships, but they do also differ in sign depending on the diagnosis and the degree of pathological changes.

A Real-World Study of Cerebral 99mTc-TRODAT-1 Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter in Patients with Parkinson Disease from a Tertiary Hospital in Brazil.

BackgroundStudies on the routine clinical use of dopamine transporter (DAT) imaging have largely been conducted in Europe and the United States. In this real-world study, we investigated the use of cerebral 99mTc-TRODAT-1 SPECT imaging of DAT in patients with Parkinson disease (PD) at a tertiary hospital in Brazil.Material/MethodsWe included 119 patients with suspected PD or clinically unclear parkinsonism who underwent brain scintigraphy with 99mTc-TRODAT-1 during a 3-year period. Additionally, a brief interview was conducted with the physician who requested the scan to determine the usefulness of the method in clinical decision-making.ResultsRegarding the scan requests, most were intended to evaluate or confirm dopaminergic denervation (69%), distinguish PD from essential tremor (10%), or distinguish degenerative parkinsonism from drug-induced parkinsonism (6%). Data analysis showed that scintigraphy with 99mTc-TRODAT-1 was useful in 85% of cases, changing the management of 75% of the patients who underwent a scan. The majority of physicians who requested the scan were neurologists, and 54% were self-reported movement disorder specialists. An inappropriate use of DAT imaging was seen in 5% of cases.ConclusionsThis study demonstrated that brain scintigraphy with the DAT ligand 99mTc-TRODAT-1 may influence diagnostic or therapeutic interventions, meaning that Brazilian physicians who requested the exam have taken in vivo DAT results into account at the time of clinical decision-making.

PLGA Nanoparticles for Nose to Brain Delivery of Clonazepam: Formulation, Optimization by 32 Factorial Design, In Vitro and In Vivo Evaluation.

Intranasal administration of biodegradable nanoparticles has been extensively studied for targeting the drug directly to CNS through the olfactory or trigeminal route bypassing the blood brain barrier. The objective of the present study was to optimize Clonazepam loaded PLGA nanoparticles (CLO-PNPs) by investigating the effect of process variables on the responses using 32 full factorial design. Effect of two independent factors-amount of PLGA and concentration of Poloxamer 188, were studied at low, medium, and high levels on three dependent responses-%Entrapment efficiency, Particle size (nm), and % cumulative drug release at 24hr. %EE, Particle size, and %CDR at 24hr of the optimized batch was 63.7%, 165.1 nm, and 86.96%, respectively. Nanoparticles were radiolabeled with 99mTc and biodistribution was investigated in BALB/c mice after intranasal and intravenous administrations. Significantly higher brain/blood uptake ratios and AUC values in the brain following intranasal administration of CLO-PNPs indicated more effective brain targeting of CLO. Higher brain uptake of intranasal CLO-PNPs was confirmed by rabbit brain scintigraphy imaging. A histopathological study performed on goat nasal mucosa revealed no adverse response of nanoparticles. TEM image exhibited spherical shaped particles in the nano range. DSC and XRD studies suggested Clonazepam encapsulation within the PLGA matrix. The onset of occurrence of PTZ-induced seizures in rats was significantly delayed by intranasal nanoparticles as compared to intranasal and intravenous CLO-SOL. This investigation exhibits rapid rate and higher extent of CLO transport in the brain with intranasal CLO-PNPs suggesting a better option as compared to oral and parenteral route in the management of acute status epilepticus.

Cerebral distribution of cerebral emboli in patients with patent foramen ovale using 99MTC-MAA brain SPECT

One of the etiologies of stroke, especially in younger patients, is patent foramen ovale (PFO). The aim of this study is distribution of brain emboli in patients with PFO. We injected 99mTc-macroaggragated albumin (MAA) in 51 patients, while accomplishing valsalva maneuver, then they underwent brain scintigraphy. The most intensity of MAA uptake was respectively in cerebellar, occipital, frontal and temporoparietal regions. The study demonstrated that posterior circulation is dominant region of brain involve by cardiac emboli in subjects with PFO.

Which of the branched-chain amino acids increases cerebral blood flow in hepatic encephalopathy? A double-blind randomized trial.

Branched-chain amino acids increase the brain perfusion of patients with hepatic encephalopathy (HE), but the amino acid and the mechanisms involved are still unknown. This study compared brain perfusion and clinical improvement during leucine or isoleucine supplementation. After randomization, 27 subjects with cirrhosis and HE received leucine or isoleucine supplements for one year. Brain single Photon Emission Computed Tomography (SPECT) and dynamic brain scintigraphy (DBS) were performed pretreatment and at 1, 8 and 12 months of supplementation. Brain perfusion was increased only in the isoleucine group at 8 months of treatment by both SPECT and DBS (p < 0.001 and p = 0.05, respectively) and by SPECT at the 12th month (p < 0.05). This was associated with hepatic encephalopathy improvement at 8 and 12 months (p = 0.008 and 0.004, respectively), which was not observed in the leucine group (p = 0.313 and 0.055, respectively). Isoleucine supplementation achieved a better impact on brain perfusion restoration in HE.

Iodine-123 Ioflupane Scintigraphy for the Diagnosis of Lewy Body Disease Presenting as a Posterior Cortical Atrophy

We report the case of a 80-year old man who was admitted for loss of autonomy due to repeated falls and cognitive decline. The only symptom reported by the patient was difficulties with judging distances. Neurological examination revealed a transient extrapyramidal syndrome due to treatment with risperidone for visual hallucinations, but more importantly, a marked impairment of higher visual functions. Computerized tomography showed bilateral occipital lobe atrophy. Since Lewy body disease is a rare cause of Posterior Cortical Atrophy and given the visual hallucinations, we performed a 123-I-ioflupane brain scintigraphy which confirmed the diagnosis. To our knowledge, this is the first application of ioflupane-single photon emission computerized tomography in the diagnostic workup of a patient with Benson’s syndrome.

Use of 18FFDG PET/CT in Patients with Acute Ischemic Stroke

Introduction: Brain scintigraphy is one of the basic branches of nuclear medicine, which plays an important role in the diagnosis of neurological diseases. Functional neuroimaging techniques involve both SPECT and PET. More widely application found the coregistration of SPECT/CT and SPECT/MRI that integrate functional nuclear medicine with morphological images. Objective: To study the usefulness of (18F)-FDG PET/CT in patients with acute ischemic cerebral stroke. Material and methods: A total of 16 cases (10 males and 6 females, aged between 39 and 80) with acute ischemic cerebral stroke, admitted to First Clinic of Neurology at UMBAL `Sveta Marina` during the period of 2008-2013 year were included in the study. (18F)-FDG PET/CT scans were obtained by means of Phillips Gemini TF machinery, following the corresponding standard protocols. Results: In all patients were visualized hypodense and hypometabolic zones, corresponding to the location of brain infarction and border regions of reduced glucose metabolism, reflecting the so called `penumbra`. Conclusion: Based on the literature data and our own results, we confirm the clinical application of (18F)-FDG PET/CT in patients with acute ischemic strokes. We suggest that this modern method of co-registration might be useful for assessment of structural and metabolic cerebral disorders and possesses an important diagnostic and prognostic significance for the disease outcome.

Interest and role of brain scintigraphy in the diagnosis of dementia in 2014

Isotopic functional brain imaging is an important tool for the diagnosis and assessment of Alzheimer's disease and related disorders. This paper is a review of currently available radiotracers for PET and SPECT imaging, making a distinction between so-called topographical and pathophysiological markers. The respective indications and limitations of the ligands are presented.

PATHOLOGY OF CEREBROVASCULAR ANGIOARCHITECTONICS AND MICROCIRCULATION IN ETIOLOGY AND PATHOGENESIS OF ALZHEIMER'S DISEASE

There have recently appeared many reports dedicated to cerebral hemodynamics disorders during AD progression. However, certain aspects of cerebral blood flow and microcirculation during AD are not fully understood. This research focuses on the identification of cerebral angioarchitectonics features and the study of microcirculatory disorders arising during AD progression, and on the determination of their importance in AD etiology and pathogenesis. 164 patients participated in the research: Test Group - 81 patients with different AD stages; Control Group - 83 patients with etiologically different neurodegenerative brain lesions accompanied by manifestations of dementia and cognitive impairment of varying severity but without AD. All patients underwent: assessment of cognitive function (MMSE), severity of dementia (CDR) and AD stages (TDR), laboratory examination, computed tomography (CT), magnetic resonance imaging (MRI), brain scintigraphy (SG), rheoencephalography (REG) and cerebral multi-gated angiography (MUGA). All Test Group patients, with both pre-clinical and clinical AD stages, had disorders of cerebral microcirculation manifested in dyscirculatory angiopathy of Alzheimer's type (DAAT), namely: capillary bed reduction in the hippocampus and frontal-parietal regions; multiple arteriovenous shunts in the basin of arterial branches supplying the hippocampus and fronto-parietal brain regions; early venous dumping of arterial blood through these shunts with simultaneous filling of arteries and veins; abnormally enhanced lateral venous trunks receiving blood from the arterio-venous shunts; anomalous venous congestion at the border of frontal and parietal lobe caused by the increased blood inflow from the arterial-venous shunts; increased looping of distal intracranial arterial branches. Control group patients had no combinations of such changes in angioarchitectonics and microcirculation. The primary basis for these changes is cerebral microcirculation disorders manifested in capillary bed reduction and decreased blood flow to cerebral tissues. The process is accompanied by natural arteriovenous shunts leading to arterial blood dumping to the venous bed followed by temporal and fronto-parietal lateral veins enlargement and subsequent blood congestion. Finally, long-term chronic hypoperfusion of these areas follows causing specific cerebral tissue hypoxia and ischemia. These changes may then affect amyloid beta metabolism and facilitate its accumulation in brain tissue stimulating AD progression. Patient Sh., 68 years old. Angiogram of the right internal carotid artery; TDR-3; lateral projection, arterial phase; Absence of atherosclerotic changes of intracranial vessels. 1: Development of hypovascular region; 2: Multiple arteriovenous shunts in fronto-parietal and temporal regions Patient O., 72 years old. Angiogram of the left internal carotid artery; TDR-2; lateral projection, capillary phase; Absence of atherosclerotic changes of intracranial vessels. 1: Development of hypovascular area; 2: Multiple arteriovenous shunts in fronto-parietal and temporal regions; 3: The development of early venous discharge in the temporal and fronto- parietal region. Simul-taneous filling of arteries and veins. Patient P., 75 years old. Angiogram of the right internal carotid artery; TDR-3; lateral projection, venous phase; 4: The development of pathologically enlarged veins that receive blood from arteriovenous shunts in the temporal and fronto-parietal region; 5: Blood congestion on the border of the fronto-parietal region. Patient P., 75 years old. Angiogram of the right internal carotid artery; TDR-3; lateral projection, early arterial phase; Absence of atherosclerotic changes of intracranial vessels. 1: Development of hypovascular area; 6: Multiple loop formation.

Paliperidone microemulsion for nose-to-brain targeted drug delivery system: pharmacodynamic and pharmacokinetic evaluation

Objective: The objective of present study was to develop and evaluate paliperidone (PALI) loaded microemulsion (PALI-ME) for intranasal delivery in the treatment of schizophrenia.Material and methods: The PALI-ME was formulated by the spontaneous microemulsification method and characterized for physicochemical parameters. Pharmacodynamic assessments (apomorphine-induced compulsive behavior and spontaneous motor activity) were performed using mice. All formulations were tagged with 99mTc (technetium). Pharmacokinetic evaluation of PALI in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging was performed in rabbits.Results and discussion: PALI-ME was found stable with average droplet size of 20.01 ± 1.28 nm. In pharmacodynamic studies, significant (p < 0.05) deference in parameters estimated, were found between the treated and control groups. 99mTc-tagged PALI solution (PALI-SOL)/PALI-ME/PALI muco-adhesive ME (PALI-MME) was found to be stable and suitable for in vivo studies. Brain-to-blood ratio at all sampling points up to 8 h following intranasal administration of PALI-MME compared to intravenous PALI-ME was found to be 6–8 times higher signifying greater extent of distribution of the PALI in brain. Rabbit brain scintigraphy demonstrated higher intranasal uptake of the PALI into the brain.Conclusion: This investigation demonstrates a prompt and larger extent of transport of PALI into the brain through intranasal PALI-MME, which may prove beneficial for treatment of schizophrenia.

Evaluation of brain targeting efficiency of intranasal microemulsion containing olanzapine: pharmacodynamic and pharmacokinetic consideration

The objective of this study was to develop and evaluate olanzapine (OZP) -loaded microemulsions (OZPME) for intranasal delivery in the treatment of schizophrenia. The OZPME was formulated by the spontaneous microemulsification method and characterized for physicochemical parameters. Pharmacodynamic assessments (apomorphine – induced compulsive behavior and spontaneous locomotor activity) were performed using mice. All formulations were radiolabeled with technetium-99 (99mTc), and biodistribution of drug in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging in rabbits was performed to determine the uptake of the OZP into the brain. OZPME were found clear and stable with average globule size of 23.87 ± 1.07 nm. In pharmacodynamic assessments, significant (p < 0.05) difference in parameters estimated were found between the treated and control groups. 99mTc-labeled OZP solution (OZPS)/OZPME/OZP mucoadhesive microemulsion (OZPMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of OZPMME compared to intravenous OZPME was found to be five to six times higher signifying larger extent of distribution of the OZP in brain. Drug targeting efficiency and direct drug transport were found to be highest for intranasal OZPMME, compared to intravenous OZPME. Furthermore, rabbit brain scintigraphy also demonstrated higher intranasal uptake of the OZP into the brain. This investigation demonstrates a prompt and larger extent of transport of OZP into the brain through intranasal OZPMME, which may prove beneficial for treatment of schizophrenia.

Microemulsion-based drug delivery system for transnasal delivery of Carbamazepine: preliminary brain-targeting study

This study reports the development and evaluation of Carbamazepine (CMP)-loaded microemulsions (CMPME) for intranasal delivery in the treatment of epilepsy. The CMPME was prepared by the spontaneous emulsification method and characterized for physicochemical parameters. All formulations were radiolabeled with 99mTc (technetium) and biodistribution of CMP in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging in rats was also performed to determine the uptake of the CMP into the brain. CMPME were found crystal clear and stable with average globule size of 34.11 ± 1.41 nm. 99mTc-labeled CMP solution (CMPS)/CMPME/CMP mucoadhesive microemulsion (CMPMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMPMME compared to intravenous CMPME was found to be 2- to 3-fold higher signifying larger extent of distribution of the CMP in brain. Drug targeting efficiency and direct drug transport were found to be highest for CMPMME post-intranasal administration compared to intravenous CMP. Rat brain scintigraphy also demonstrated higher intranasal uptake of the CMP into the brain. This investigation demonstrates a prompt and larger extent of transport of CMP into the brain through intranasal CMPMME, which may prove beneficial for treatment of epilepsy.

Radiolabeled neurogenesis marker imaging: A revolution in the neurological diseases management?

A reduced rate of neurogenesis occurs in the adult brain of patients with neurological diseases, with the rate of new neuron proliferation not sufficient to replace neuron loss. Neurogenesis can be induced by several factors, including basic fibroblast growth factor, epidermal growth factor, and brain-derived neurotrophic factor.Neurogenesis determination is a valuable parameter for determining disease progression and monitoring various treatments. Currently, neurogenesis detection is possible by invasive methods, such as bromodeoxyuridine (BrdU) cell labeling and immunohistological analysis of immature neuron markers. However, these are not compatible with alive model examination. Neurogenesis detection by noninvasive methods, such as radiolabeling of specific antibodies and scintigraphy imaging, could shed light on immature neuronal markers.We propose that brain scintigraphy after radiolabeling of a specific antibody of an immature neuronal marker is a useful new modality for neurogenesis detection and that it would aid the management of neurological diseases.

Do non-motor symptoms in Parkinson's disease differ from essential tremor before initial diagnosis? A clinical and scintigraphic study

BackgroundNon-motor symptoms (NMS) in Parkinson's disease (PD) are common, increase the patients' disability and have a significantly negative impact on their quality of life. Essential tremor (ET) is also affected by non-motor symptoms and often enters into the differential diagnosis with PD. Brain scintigraphy with [123I]β-CIT SPECT is a technique used to facilitate differential diagnosis between PD and ET. MethodsWe evaluated both motor impairment (MDS-UPDRS-III) and non-motor symptoms (NMSQuest) in patients who underwent a [123I]β-CIT SPECT examination for diagnostic purposes. Both the clinical and the scintigraphic data obtained from the selected PD (n = 31) and ET (n = 22) patients were compared. ResultsWe did not detect a significant difference in the total number of NMS reported by either PD (10.4 ± 4.9) or ET patients (8.41 ± 3.3). PD patients reported more drooling (29%), hyposmia (32.2%), hallucinations (19.3%), difficulty in concentrating (51.6%), orthostatic dizziness (67.7%), falling (19.3%), vivid dreams (32.2%), REM sleep behavior disorder (58%), and diplopia (22.5%) compared with ET patients. PD patients who complained of drooling, orthostatic dizziness, and diplopia had greater denervation of the caudata than did the PD patients who did not report the same symptoms. The differences observed were not associated with differences in age, sex, UPDRS-III score, and the presence/absence of tremor. ConclusionsThe declaration of non-motor symptoms is influenced by subjective factors that are widely suggestible. When analyzed early and before receiving a definitive diagnosis, PD patients complain of specific symptoms that seem to depend on different pathogenetic mechanisms.