Progressive supranuclear palsy and corticobasal degeneration: Diagnostic challenges and clinicopathological considerations.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are two atypical parkinsonian syndromes first described half a century ago. The spectrum of these conditions as well as, more generally, the concept of tauopathy have dramatically changed over the past decade and especially in recent years. In particular, clinicopathological correlations have led to the description of several subtypes of these diseases and the features they share with other neurodegenerative diseases. The present paper is a review of how the concepts of PSP and CBD have evolved over time. In particular, it focuses on the different presentations of the disease and the overlapping syndromes that can complicate the differential diagnoses. Also discussed are some of the tools that may prove useful in making a diagnosis. Indeed, differential diagnosis issues are of particular importance in light of the likely emergence of pathology-specific disease-modifying therapies in the near future.

Molecular imaging in the diagnosis of Alzheimer's disease and related disorders.

INTRODUCTION: The diagnosis of Alzheimer's disease (AD) and its related disorders rely on clinical criteria. There is, however, a large clinical overlap between the different neurodegenerative diseases affecting cognition and, frequently, there are diagnostic uncertainties with atypical clinical presentations. Current clinical practices can now regularly use positron emission tomography (PET) and single-photon emission computed tomography (SPECT) molecular imaging to help resolve such uncertainties. The Neurology Group of the French Society of Nuclear Medicine and Federations of Memory, Resources and Research Centers have collaborated to establish clinical guidelines to determine which molecular imaging techniques to use when seeking a differential diagnosis between AD and other neurodegenerative disorders affecting cognition. STATE OF KNOWLEDGE: According to the current medical literature, the potential usefulness of molecular imaging to address the typical clinical criteria in common forms of AD remains modest, as typical AD presentations rarely raise questions of differential diagnoses with other neurodegenerative disorders. However, molecular imaging could be of significant value in the diagnosis of atypical neurodegenerative disorders, including early onset, rapid cognitive decline, prominent non-amnestic presentations involving language, visuospatial, behavioral/executive and/or non-cognitive symptoms in AD, or prominent amnestic presentations in other non-AD dementias. CONCLUSION AND PERSPECTIVE: The clinical use of molecular imaging should be recommended for assessing cognitive disturbances particularly in patients with early clinical onset (before age 65) and atypical presentations. However, diagnostic tools should always be part of the global clinical approach, as an isolated positive result cannot adequately establish a diagnosis of any neurodegenerative disorder.

Brain FDG-PET correlates of saccadic disorders in early PSP.

BACKGROUND: New diagnostic criteria of Progressive Supranuclear Palsy (PSP) have highlighted the interest of Eye Movement Records (EMR) at the early stage of the disease. OBJECTIVES: To investigate the metabolic brain correlates of ocular motor dysfunction using [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in early PSP. METHODS: Retrospective observational descriptive study on longitudinal data with patients who underwent EMR and FDG-PET at the stage of suggestive and possible PSP according to Movement Disorders Society criteria. Longitudinal follow-up enables to confirm diagnosis of probable PSP. Using the Statistical Parametric Mapping software, we performed whole-brain voxel-based correlations between oculomotor variables and FDG-PET metabolism. RESULTS: Thirty-seven patients with early PSP who fulfilled criteria of probable PSP during the follow-up were included. Decrease in the gain of vertical saccades correlated with reduced metabolism in Superior Colliculi (SC). We also found a positive correlation between mean velocity of horizontal saccades and SC metabolism as well as dorsal nuclei in the pons. Finally, increase in horizontal saccades latencies correlated with decrease of posterior parietal metabolism. CONCLUSIONS: These findings suggest the early involvement of SC in saccadic dysfunction in the course of PSP.

[Use of CSF biomarkers in the diagnosis of Alzheimer's disease in clinical practice]. / Utilisation des biomarqueurs du LCR dans le diagnostic de la maladie d'Alzheimer en pratique clinique.

INTRODUCTION: The diagnosis of Alzheimer's disease (AD) currently relies on clinical criteria that are primarily based on the presence of an amnestic syndrome of the mesial temporal lobe type. In recent years, new diagnostic tools have been developed, such as the possibility of measuring a set of proteins directly involved in the pathophysiological process of AD. A profile suggestive of AD has been defined, characterized by decreased beta-amyloid peptide, combined with increased Tau protein and phopho-Tau. STATE OF KNOWLEDGE: According to current data available in the medical literature, the potential usefulness of CSF biomarkers in the common forms of AD fulfilling usual clinical criteria remains modest. In contrast however, they could be of significant help in the diagnosis of early-onset AD, in particular in atypical forms with prominent non-memory impairment (involving vision, language or behavior). In addition, due to their close relationship with the pathological process, they bring useful prognosis information upon the aggressiveness of the disease. CONCLUSION AND PERSPECTIVE: Taken together, in the current state of knowledge, use of CSF biomarkers in clinical practice should first be recommended for the assessment of early-onset cognitive disturbances, in particular when initial symptoms are of a non-memory type. Their development, however, offers new avenues in the fields of clinical and pharmacological research.

[Diagnosis of vitamin B12 deficiency: a case illustrating diagnostic pitfalls]. / Diagnostic d'une carence en vitamine B12 ou le signe de l'ordonnance.

INTRODUCTION: Vitamin B12 deficiency is a longstanding public health problem which affects more than 20% of the elderly population. Among multiple causes of vitamin B12 deficiency, Biermer's disease is currently mentioned in about 25% of the cases. OBSERVATION: We report the case of a 71-year-old woman, taking folate substitution therapy who, over 2 years, progressively developed spinal combined sclerosis, subacute dementia and severe neuropathy leading to a bedridden state. The initial assessment revealed normocytic anemia, without vitamin B12 deficiency and without increased plasma level of biological markers. The plasma folate level was high. Vitamin B12 assay was repeated leading to the diagnosis of deficiency associated with the presence of intrinsic factor antibodies. DISCUSSION: This observation illustrates the broad spectrum of clinical presentations of vitamin B12 deficiency. In the present case, the lack of sensitivity of biological markers delayed diagnosis and had a dramatic impact on outcome. This case highlights the importance of promoting factors such as isolated folate substitution in B12 deficient patients.

[Weight loss, dementia and ataxia susceptible to doxycycline: a likely new case report caused by T. whipplei]. / Prise de poids, démence et syndrome cérébelleux sensible à la doxycycline : un probable nouveau cas lié à T. whipplei.

INTRODUCTION: Whipple's disease is a rare infectious disease due to Tropheryma whipplei, a bacterium rarely causing severe localized neurological infection (only 25 cases reported in the literature), which are more often diagnosed by a positive T. whipplei PCR performed on cerebrospinal fluid. CASE REPORT: We report the third case of progressive dementia associated with obesity and ataxia in a 52-year-old man. Classic laboratory results performed to identify the etiology of the clinical features were non-contributive: only a saliva T. whipplei PCR was strongly positive and the Western blot serology has detected an asymptomatic carriage profile. The (18)FDG-PET highlighted a frontal area hypometabolism. An antibiotic treatment by doxycycline allowed a partial regression of the neurological manifestations, a weight loss and a significant improvement of the (18)FDG frontal hypometabolism. CONCLUSION: Progressive dementia associated with ataxia and obesity is a new clinical syndrome caused by T. whipplei. Antibiotic test by doxycycline can help to the diagnosis and (18)-FDG could facilitate the follow-up.