Cerebrospinal fluid (CSF) biomarkers remain the gold standard for fluid-biomarker-based diagnosis of Alzheimer’s disease (AD) during life. Plasma biomarkers avoid lumbar puncture and allow repeated ...sampling. Changes of plasma phospho-tau-181 in AD are of comparable magnitude and seem to parallel the changes in CSF, may occur in preclinical or predementia stages of the disease, and may differentiate AD from other causes of dementia with adequate accuracy. Plasma phospho-tau-181 may offer a useful alternative to CSF phospho-tau determination, but work still has to be done concerning the optimal method of determination with the highest combination of sensitivity and specificity and cost-effect parameters.
Summary
Although daytime sleepiness is commonly associated with obstructive sleep apnoea (OSA), the relationship between OSA severity and subjective sleepiness has been documented elusive. This study ...aimed to identify clinical and polysomnographic determinants of subjective sleepiness among patients suspected of having OSA. A sleep clinic‐based sample of 915 patients was interviewed with a structured questionnaire and underwent diagnostic overnight polysomnography. Subjective sleepiness was quantified by Epworth Sleepiness Scale (ESS). Excessive daytime sleepiness (defined as ESS score > 10) was present in 38.8% of patients. In multiple linear regression analysis, respiratory disturbance index RDI; used to define (whenever RDI was >5) and quantify OSA, depression and diabetes were the most important determinants of ESS score accounting for 17%, 11% and 6% of its variability respectively. Chronic obstructive pulmonary disease (COPD), stroke, heart disease, alcohol use and body mass index were less important determinants of ESS score explaining 1–3% of its variability. In conclusion, OSA should not be considered the sole potential cause of increased subjective sleepiness in patients suspected of having OSA. Primarily depression and diabetes, but also COPD, stroke, heart disease, alcohol use and increased body mass index may contribute to increased subjective sleepiness.
Analysis of classical cerebrospinal fluid biomarkers, especially when incorporated in a classification/diagnostic system such as the AT(N), may offer a significant diagnostic tool allowing correct ...identification of Alzheimer’s disease during life. We describe four patients with more or less atypical or mixed clinical presentation, in which the classical cerebrospinal fluid biomarkers amyloid peptide with 42 and 40 amino acids (Aβ42 and Aβ40, respectively), phospho-tau (τP-181) and total tau (τΤ) were measured. Despite the unusual clinical presentation, the biomarker profile was compatible with Alzheimer’s disease in all four patients. The measurement of classical biomarkers in the cerebrospinal fluid may be a useful tool in identifying the biochemical fingerprints of Alzheimer’s disease, especially currently, due to the recent approval of the first disease-modifying treatment, allowing not only typical but also atypical cases to be enrolled in trials of such treatments.
•Hydrocephalus is rarely reported in patients with diffuse glioma.•We describe a patient with a low-grade glioma presenting a complex phenotype initially masquerading as hydrocephalus of unknown ...etiology.•The exact pathophysiological mechanism underlying hydrocephalus in the setting of diffuse glioma remains to be elucidated.•Caution is advised regarding hydrocephalus of unknown etiology, reevaluation is necessary.
Occult paroxysmal atrial fibrillation (PAF) is a common and potential treatable cause of cryptogenic stroke (CS). We sought to prospectively identify independent predictors of atrial fibrillation ...(AF) detection in patients with CS and sinus rhythm on baseline electrocardiogram (ECG), without prior AF history. We had hypothesized that cardiac arrhythmia detection during neurosonology examinations (Carotid Duplex (CDU) and Transcranial Doppler (TCD)) may be associated with higher likelihood of AF detection.
Consecutive CS patients were prospectively evaluated over a six-year period. Demographics, clinical and imaging characteristics of cerebral ischemia were documented. The presence of arrhythmia during spectral waveform analysis of CDU/TCD was recorded. Left atrial enlargement was documented during echocardiography using standard definitions. The outcome event of interest included PAF detection on outpatient 24-h Holter ECG recordings. Statistical analyses were performed using univariate and multivariate logistic regression models.
A total of 373 patients with CS were evaluated (mean age 60 ± 11 years, 67% men, median NIHSS-score 4 points). The rate of PAF detection of any duration on Holter ECG recordings was 11% (95% CI 8%-14%). The following three variables were independently associated with the likelihood of AF detection on 24-h Holter-ECG recordings in both multivariate analyses adjusting for potential confounders: age (OR per 10-year increase: 1.68; 95% CI: 1.19-2.37;
= 0.003), moderate or severe left atrial enlargement (OR: 4.81; 95% CI: 1.77-13.03;
= 0.002) and arrhythmia detection during neurosonology evaluations (OR: 3.09; 95% CI: 1.47-6.48;
= 0.003).
Our findings underline the potential utility of neurosonology in improving the detection rate of PAF in patients with CS.
Cerebrospinal fluid (CSF) biomarkers have been increasingly studied in dementia clinical and differential diagnosis.
We assessed levels of total tau protein (tauT), tau phosphorylated at threonine ...181 (tau P-181), and beta-amyloid1-42 (A beta 42) in 34 patients with frontotemporal lobar degeneration (FTLD), 76 Alzheimer disease (AD) cases, and 93 controls (CTRL). Double sandwich enzyme-linked immunosorbent assays (Innogenetics) were used for measurements.
Total tau was significantly increased and A beta 42 decreased in FTLD and AD patients as compared with CTRL. CSF tau P-181 levels were significantly increased only in AD. The tauT/A beta 42 ratio successfully discriminated FTLD from CTRL with a 86.7% specificity and 80.6% sensitivity, whereas the tauT alone was more specific (95.7%) but less sensitive (64.75%). For the discrimination of FTLD from AD, tauT/A beta 42 ratio was better (90.3% sensitivity and 64.5% specificity) compared with the other biomarkers alone or in combination, whereas tau P-181 was less sensitive but more specific (68.4% and 85.7%, respectively). Subtype analysis revealed that the most AD-like profile of biomarkers were observed in FTLD with motor neuron signs, whereas the most non-AD profile were observed in patients with primary progressive aphasia.
Combined analysis of CSF biomarkers may be useful for the best possible antemortem discrimination of FTLD from AD.
To investigate the frequency and causes of early-onset dementia (EOD) in consecutive patients in a highly specialized dementia referral center, focusing on unusual cases, particularly with early ...and/or rapid onset, in Athens, Greece.
Patients referred for dementia diagnosis according to specific referral criteria during a 3 years period. We examined the distribution of patients diagnosis and differences in sex, education, dementia severity, cognitive function, and the duration of disease (from onset to referral) between the EOD (<65 y) and the late-onset dementia (LOD) groups.
From a total of 260 consecutive demented patients, there were 114 EOD patients or 44% of all demented patients. No significant differences were observed between the EOD and LOD groups in cognitive or behavioral measures. However, the duration from onset to consultation was significantly longer in the EOD group. Also, in the EOD group, the rates of patients with Alzheimer disease and Parkinson disease dementia were relatively low and the rate of patients with frontotemporal lobar degeneration was relatively high and the proportion of secondary dementias was high.
We conclude that EOD patients are more likely to be seen in specialized settings. The underlying diseases are considerably different in EOD compared with LOD. Secondary causes are often found in patients with EOD. Patients with EOD had an unexpectedly longer time-to-diagnosis than patients with LOD. This argues for a need of better education about the clinical presentation of dementia in the young and middle aged.
Summary
Purpose: Epileptiform discharges (EDs) may be part of the internal arousing stimuli that affect the quality of sleep in patients with epilepsies. We studied the association between EDs and ...sleep phasic phenomena, and its relevance to seizure control in 19 patients with juvenile myoclonic epilepsy (JME).
Methods: We analyzed the first cycle of non‐REM (rapid eye movement) sleep in 22 sleep‐deprived electroencephalography (EEG) studies and classified EDs within the cyclical alternating pattern (CAP) frame, grouping separately the EDs that occurred at the transition between phases (B to A and A to B).
Results: Within CAP periods, 36.7% of EDs occurred in A phase, 26.7% in B phase, 31.5% at “B to A” transition, and 3% at “A to B” transition. Poor seizure control was strongly associated with increased EDs in phase B (p = 0.0016) and at the “B to A” transition (p = 0.002), but marginally with increased EDs in phase A (p = 0.03). Focal spikes were increased in phase B.
Discussion: EDs are facilitated by increased vigilance (A phase), but they may also enhance CAP cycling by generating A phases when those that occur at the “B to A” transition are interpreted as successfully breaking through the state of reduced arousal (phase B) because of increased epileptic pressure. This promotes sleep instability and further fosters epileptic activity, and conceivably seizures. This hypothesis is also supported by the strong correlation between EDs during phase B (including “B” and “B to A”) and poor seizure control. The enhanced nonlocalizing focal spikes in phase B may reflect successful inhibition of generalized EDs.
A 76-year-old man complained of daytime sleepiness and frequent arousals from sleep due to a sense of whole-body restlessness, followed by automatic frequently injurious behavior. A ...video-polysomnography revealed periodic leg movements (figure) and arousal followed by sleep episodes while standing, rhythmic marching, and falling (videos 1 and 2 on the Neurology(R) Web site at Neurology.org). A reevaluation of his history revealed symptoms compatible with restless legs syndrome (RLS). Rotigotine super(1) proved very effective, supporting the diagnosis of RLS. Periodic leg movement disorder leading to sleep-related rhythmic movement disorder could also be considered. Automatic behavior denotes severe sleep deprivation super(2) and may represent a non-REM parasomnia. Severe RLS may present with automatic behavior complicating its diagnosis.
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