Amyloid imaging

Molecular neuroimaging techniques such as PET are proving valuable in the early and differential diagnosis of Alzheimer's disease (AD).With the advent of new therapeutic strategies aimed at reducing β-amyloid (Aβ) burden in the brain to potentially prevent or delay functional and irreversible cognitive loss, there is increased interest in developing agents that allow assessment of Aβ burden in vivo. Amyloid imaging with PET has proven useful in the discrimination of dementias, showing significantly higher Aβ burden in the gray matter of AD patients when compared with healthy controls or patients with frontotemporal dementia. ApoE ε4 carriers, independent of diagnosis or disease severity, present with higher Aβ burden than non-ε4 carriers. Amyloid imaging matches histopathological reports in aging and dementia, reflecting the true regional density of Aβ plaques in cortical areas. It also appears to be more sensitive than FDG-PET for the diagnosis of AD. In healthy older people there is an increasing prevalence of amyloid positive scans with age, rising from 20% in the seventh decade to 60% in the ninth decade. Of people with mild cognitive impairment (MCI), 40-60% present with detectable cortical Aβ deposition. In both groups, Aβ deposition is associated with a higher risk for cognitive decline and dementia due to AD. These observations suggest that Aβ deposition is not part of normal aging, supporting the hypothesis that it occurs well before the onset of symptoms and is likely to represent preclinical AD in asymptomatic persons and prodromal AD in MCI. Further longitudinal observations, coupled with different disease-specific tracers and biomarkers, are required to confirm this hypothesis and further elucidate the precise role of Aβ deposition in the course of AD.     

Insertions in the prion protein gene in atypical dementias.

A number of mutations have been demonstrated in the open reading frame (ORF) of the prion protein (PrP) gene in patients with familial Creutzfeldt-Jakob disease or Gerstmann-Str?ussler syndrome. On the basis of detecting an insertion in the ORF of the PrP gene in a patient originally suspected to be suffering from familial Alzheimer-type dementia, we screened 101 individuals with atypical dementias for the known PrP gene mutations. Insertions were found in five individuals, whereas none of the other reported mutations in the PrP gene was detected in the present study. One of the five insertions was larger than that described previously, suggesting that the individuals with these mutations are unlikely to be all lineally related and that insertions in the PrP gene may not be uncommon in prion diseases.     

Amyloid imaging]

Amyloid imaging has recently emerged as a non-invasive neuroimaging technique to visualize the accumulation of amyloid-beta in living brain. Several modalities such as PET, SPECT, MRI, and optical imaging has been adopted for this purpose, the nuclear medicine technique of PET firstly put it to practical use because of its high sensitivity. Among many radioligand tracers proposed, Pittsburgh Compound-B (PIB) has successfully spread over the world as a standard amyloid imaging probe. Several lines of evidence from PIB-PET study have suggest that the accumulation of amyloid beta start during the preclinical stage of Alzheimer's disease (AD) and reaches plateau phase before or during the MCI stage. Therefore, the amyloid imaging may be useful as a biomarker of AD, not only for the very early specific diagnosis, but also for the monitoring the therapeutic effect with agents that reduce the accumulation of amyloid-beta in the brains of AD. The amyloid imaging technique is also useful to differentiate non-AD type degenerative disorders such as argiophilic grain dementia and neurofibrillary tangle dominant dementia, which are cumulatively called as tauopathies. In order to evaluate its diagnostic power, and pathophysiological significance of accumulation, further prospective study and pathology-PET comparison are essential.     

Amyloid imaging in Alzheimer's disease

PURPOSE OF REVIEW: This paper reviews the progress in developing amyloid imaging ligands to be used to measure amyloid in vivo in the brain of patients with Alzheimer's disease. RECENT FINDINGS: Four radioligands, [18F] 1,1-dicyano-2-[6-(dimethylamino)-2-naphtalenyl] propene or 18F-FDDNP, N-methyl [11C] 2-(4'-methylaminophenyl)-6-hydroxy-benzothiasole or 11C-PIB, 4-N-methylamino-4'-hydroxystilbene [11C] or SB13 and 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole or 11C-BF-227, have so far been studied in Alzheimer's disease patients and age-matched healthy controls by PET. A robust difference was observed between PIB retention in mild patients and controls. A 2-year follow-up study in mild patients showed a stable level of PIB retention and a decrease in cerebral glucose metabolism and cognition. 18F-FDDNP showed less difference between Alzheimer's disease patients and controls compared with PIB. Both ligands have detected increases in amyloid in the brain of patients with mild cognitive impairment. SUMMARY: The new PET amyloid imaging technique is a breakthrough in understanding the pathophysiological mechanisms and time course in amyloid deposits in the brain. The technique will enable early detection of Alzheimer's disease. PET amyloid imaging should be used in the evaluation of new antiamyloid therapies.     

Amyloid imaging in Alzheimer's disease

Alzheimer's disease (AD) is a complex neurodegenerative disorder of which the exact cause is still not known. There has, however, been remarkable progress in the understanding of the pathophysiological events that underlie the disease with a focus on amyloid formation. We do not know yet if amyloid is the most crucial target for an effective therapy in AD. The new amyloid PET imaging tracer ligands offer possibilities for measuring fibrillar beta amyloid (Abeta) in the brain and for studying the time course of amyloid in the brain. This opens up new possibilities for early diagnosis as well as new tools for monitoring anti-amyloid therapy in AD.     

Vaccine-associated contact paralytic poliomyelitis with atypical neurological presentation

Paralytic poliomyelitis presenting with quadriparesis, transient encephalitis and bulbar symptoms in 2 patients in close contact with recently vaccinated children with trivalent live oral polio vaccine is described. Symmetrical lower motor neuron involvement of deltoid muscles with electromyographic confirmation was found. Upper motor neuron signs, with symmetrical hyperactive deep tendon reflexes developed in the lower extremities. Poliovirus Type-2 vaccine-like strain was cultured from one patient and both patients showed significant antibody titers rises to poliovirus. Attention is drawn to the possible clinical differences between vaccine associated poliomelitis and the usual features found in wild strain poliomyelitis. It is suggested that in selected cases, non-immunized contacts be given inactivated polio-vaccine when the vaccinees are immunized with the live oral-vaccine.     

Familial dementia with Lewy bodies with an atypical clinical presentation

The authors report a case of a 64-year-old male with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) pathology at autopsy who did not manifest the core symptoms of DLB until very late in his clinical course. His initial presentation of early executive and language dysfunction suggested a cortical dementia similar to frontotemporal lobar degeneration (FTLD). Core symptoms of DLB including dementia, hallucination, and parkinsonian symptoms were not apparent until late in the course of his illness. Autopsy revealed both brainstem and cortical Lewy bodies and AD pathology. Family history revealed 7 relatives with a history of dementia including 4 with possible or probable DLB. This case is unique because of the FTLD-like presentation, positive family history of dementia, and autopsy confirmation of DLB.     

Magnetic resonance imaging and magnetic resonance spectroscopy in dementias

This article reviews recent studies of magnetic resonance imaging and magnetic resonance spectroscopy in dementia, including Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, idiopathic Parkinson's disease, Huntington's disease, and vascular dementia. Magnetic resonance imaging and magnetic resonance spectroscopy can detect structural alteration and biochemical abnormalities in the brain of demented subjects and may help in the differential diagnosis and early detection of affected individuals, monitoring disease progression, and evaluation of therapeutic effect.     

Acute motor axonal neuropathy--an atypical presentation

Guillain-Barré syndrome, an autoimmune disorder of the peripheral nervous system, is divided into several subtypes according to clinico-pathologic findings and epidemiologic characteristics. A pure motor variant without involvement of the sensory nerves has been reported in rare cases. This report details the clinical, immunologic, and serial electrophysiologic findings of two patients with an acute, exclusively motor, axonal neuropathy.     

Fulminant subacute sclerosing panencephalitis:two cases with atypical presentation

From 1972 to 2002, we diagnosed and treated 22 cases of subacute sclerosing panencephalitis. We report on two pediatric patients with fulminant subacute sclerosing panencephalitis who had atypical clinical manifestations. In both patients diagnosis was confirmed by elevated titers of CSF and serum antimeasles antibodies. Patient 1 presented with behavioral disorder, dysarthria, and drop attacks, while Patient 2 presented with partial complex seizures. Mental difficulties, personality changes, or myoclonus were not noticed in Patient 2. In both our patients stage I was not prominent, and stage II was of shortened duration. In spite of treatment with isoprinosine and interferon-alpha, both our patients deteriorated rapidly and died 2.5 and 4 months, respectively, after the onset of neurologic symptoms. Both atypical presentation and rapid clinical course observed in our patients could cause problems in making final diagnosis of subacute sclerosing panencephalitis. Therefore, subacute sclerosing panencephalitis should be included in differential diagnosis of acute unexplained encephalopathic diseases.     

Functional brain imaging applications to differential diagnosis in the dementias

PURPOSE OF REVIEW: The diagnosis of dementia rests on an improved knowledge and a better detection of early impairments, to which functional imaging can certainly contribute. RECENT FINDINGS: Progress has been observed at different levels. First, the understanding of different dementias has benefited from explorations of the neural substrate of dementia symptoms and from research into new markers. Second, diverse variables (clinical, anatomical, biochemical) have been related to impaired cerebral activity in Alzheimer's disease and other dementias, and progress in image analysis and in multimodal data acquisition has allowed a better understanding of the significance of brain activity disturbances. Third, functional imaging has been applied in well-designed clinical studies, and has provided important arguments for the diagnosis of characteristic clinical syndromes in the dementias. SUMMARY: The functioning of neural networks responsible for clinical symptoms in dementia remains an important research topic for functional imaging. The development of new tracers and new techniques for image processing should also improve the usefulness of brain imaging as a diagnostic tool.     

Giant cell angiitis of the central nervous system with atypical presentation

Giant cell angiitis of the CNS is an uncommon form of vasculitis. Neurological manifestations, both of the peripheral and CNS, are common. The most frequent manifestations are visual loss and stroke. Hemorrhagic onset is uncommon. Most cases have a fatal outcome and a tissue diagnosis is rarely established in life. We describe an unusual case of giant cell angiitis beginning as a hemorrhagic tumoral‐like lesion. The results of the histological and ultrastructural analysis have also been reported. Our case illustrates that giant cell angiitis should be considered as a cause of intracerebral hemorrhage, particularly when associated with a relapsing and remitting disease of the CNS.     

Structural imaging in cognitive impairment and the dementias: an update

PURPOSE OF REVIEW: The purpose of this review is to explore and summarize recent advances in the structural imaging of cognitive impairment and the dementias. The focus is practical, covering issues that bear relevance to clinical practice or diagnosis. Findings in mild cognitive impairment, a state preceding but not necessarily leading to dementia, are discussed. Data from dementias other than Alzheimer's disease are reviewed at some length before outlining some novel issues in Alzheimer's disease imaging. RECENT FINDINGS: A number of studies have proposed some medial temporal atrophy in mild cognitive impairment, and this may have some clinical value in predicting conversion to dementia. Data on other regions have also been proposed to predict conversion, but a number of studies on these regions have yielded entirely conflicting results. Data are also accumulating on the medial temporal lobe and other regions in non-Alzheimer's dementias. SUMMARY: The medial temporal lobe is still the region of interest when studying mild cognitive impairment and Alzheimer's disease. Medial temporal atrophy, or lack thereof, may be of some diagnostic value even in non-Alzheimer's dementias. Medial temporal atrophy, however, is not an Alzheimer's disease-specific feature. One potential approach to improve the radiological diagnosis of dementia is mapping a number of regions in order to define patterns of atrophy. At present, however, the scarcity of existing data prevents unambiguous conclusions on this issue.     

Unilateral hydrocephalus: atypical presentation of intracranial tuberculoma

A 43-year-old male presented with 3-month history of low-grade fever and headache. Radiological investigations revealed unilateral hydrocephalus. Unilateral obstruction of the foramen of Monro due to chronic tubercular ependymal inflammation was suspected and endoscopic septostomy was planned. Though ventriculo-peritoneal shunt is a simple method to treat hydrocephalus, complications related to this procedure are numerous. Neuroendoscopy is a safe method to treat hydrocephalus in selected cases, and also provides access to biopsy the lesion in question. An isolated tuberculoma obstructing the foramen of Monro was seen during endoscopy. Presentation and management of this unusual tuberculoma is reported along with a review of the pertinent literature.