Álvaro Machado

Diagnostic value of CSF protein profile in a Portuguese population of sCJD patients

The clinical diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) is difficult, and reliable markers are highly desired. In this work we assess the value of several cerebrospinal fluid (CSF) markers for sCJD diagnosis. Within the framework of the Portuguese Epidemiological Surveillance Program for Human Prion Diseases, CSF samples from 71 patients with clinically suspected sCJD, 30 definite sCJD and 41 non-CJD patients, were analysed for the presence of 14-3-3 protein. CSF levels of tau (t-tau), and phosphorylated tau (p-tau181), S-100b and β amyloid (Aβ42) proteins were determined. The influence of clinical and genetic characteristics on CSF markers sensitivity was also evaluated. Protein 14-3-3 was detected in 29/30 sCJD patients and 9/41 non-CJD patients. Extremely elevated t-tau and S-100b protein levels were found in sCJD patients, while p-tau181 levels were only slightly elevated and Aβ42 showed no differences compared to controls. 14-3-3 was the most sensitive parameter (97%), but its specificity was low (78%); sensitivity/specificity for other proteins were: S-100b—93/93%, t-tau—93/95%, with maximum accuracy being obtained by a combination of tests (14-3-3 combined with either t-tau or S-100b, or combining S-100b with t-tau/Aβ42 or p-tau/t-tau ratios). The sensitivity of 14-3-3, as well as of p-tau181/t-tau ratio, was decreased in younger patients with long disease duration, with the PrP-2 isotype and MV genotype. Both 14-3-3, t-tau and S-100b are sensitive markers for sCJD, but 14-3-3 specificity seems to be lower in this special clinical setting of rapidly progressing dementias. We propose that in cases with a 14-3-3 weak positive result, or in young patients with long disease duration, a second CSF marker would be valuable for the diagnosis of sCJD.

Intravenous thrombolysis is more effective in ischemic cardioembolic strokes than in non-cardioembolic?

UNLABELLED It was suggested that intravenous thrombolysis (IT) leads to larger extent recanalization in cardioembolic stroke. In this work we assess if this has beneficial clinical traduction. METHOD We evaluated 177 patients undergoing IT, which were categorized into cardioembolic (CE) and non-cardioembolic (NCE). National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale were compared. RESULTS The mean age was 67.4 ± 12.01 and 53.8% were male. The mean NIHSS was: 14 (admission), 9 (24 h) and 6 (discharge), similar in subgroups. The difference between NIHSS at admission and 24 hours was 4.17 ± 4.92 (CE: 4.08 ± 4.71; NCE: 4.27 ± 5.17, p=0.900) and at admission and discharge there was an average difference of 6.74 ± 5.58 (CE: 6.97 ± 5.68; NCE: 6.49 ± 5.49, p=0.622). The mRS at discharge and 3 months was not significantly different by subtype, although individuals whose event was NCE are more independent at 3 months. CONCLUSION Ours findings argue against a specific paper of IT in CE. It can result from heterogeneity of NCE group.

Septo-optic dysplasia with olfactory tract hypoplasia.

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Recurrent post-ictal hyperthermia.

An 80-year-old hypertensive man, with epileptic seizures of unknown etiology, since his 70th’s, was observed for 3 times in 4 years with self-limited right focal motor seizures with impairment of consciousness. In all these episodes, he had post-ictal global aphasia, right homonymous hemianopsia, right hemiparesis and hyperthermia (38–39.6°C). Complete clinical workups during these events (including C reactive protein, sedimentation rate, leukocyte count, thorax radiograph, urinalysis, and lumber puncture) ruled out an infection. Brain magnetic resonance imaging and computerized tomography showed old lacunar basal ganglia infarcts and generalized atrophy. Electroencephalogram (EEG) obtained in two of these episodes revealed in one of them slow background activity of 6–7 Hz, with continuous slow theta/ delta activity in left fronto-temporal region, with paroxysmal activity (spikes and sharp waves) in the same localization. The patient was treated with valproate and antipyretics (paracetamol and lysine acetylsalicylate). The hyperthermia did not respond to these drugs, but resolved spontaneously in 12–18 hours and the neurological deficits recovered within 24 hours.

Isolated oculomotor nerve paresis as the presenting sign of multiple sclerosis.

In multiple sclerosis (MS), ocular motor disturbances such as nystagmus or internuclear ophthalmoplegia are frequent and their pathophysiological processes are relatively well known. On the contrary, other rare and not so well studied manifestations such as isolated ocular motor nerve palsy may be observed and can represent a diagnostic challenge for the clinician as in the case we report. case

Phonagnosia and Inability to Perceive Time Passage in Right Parietal Lobe Epilepsy

A 25-year-old otherwise healthy epileptic woman was admitted to the hospital after four seizures without recovery of consciousness. She had experienced two previous identical seizures at ages 12 and 14 years. They all began with left oculocephalic deviation and slow left arm rising, followed by generalized tonic-clonic movements. Results on brain CT scan and EEG were normal, and she was treated for 2 years with valproate and was seizure free until age 23 years. At that time, similar seizures restarted, and after normal results on MRI scan and EEG, levetiracetam was started (1000 g/day) with seizure remission. When seen at our unit, the patient underwent a second brain MRI scan, which showed a right cortical parietal T2-hyperintense lesion without gadolinium enhancement and with discrete impairment of water molecule diffusion (Figure 1). An EEG disclosed right frontoparietal slow activity. Phenytoin (in the acute management) and carbamazepine were used, and the patient had complete seizure remission. During the following 3weeks, she started complaining that she could not recognize familiar voices, including those from relatives and famous persons, although she could identify the talking subjects if permitted to see them. She also said that she was incapable of fully acknowledging the passage of time. She was sometimes scared by stimuli that seemed to occur instantaneously but were really several seconds apart. A brain MRI scan 2 months later showed marked improvement, but a residual cortical parietal thickening remained. These data supported the clinical impression of a cortical change secondary to abundant epileptic activity.

Association of retrospective time estimation and severity of cognitive impairment

ABSTRACT Introduction. Time perception has an important role in everyday life, but is not commonly measured in clinical routine assessment of suspected cognitive impairment, given the complexity of available assessment methods. Furthermore, evidence on the pattern of retrospective time perception in neurodegenerative diseases is contradictory. Method. We asked 321 patients referred to neuropsychological assessment to retrospectively estimate the duration of the neuropsychological assessment session. We calculated the session actual duration, ratio, and accuracy of response. Patients were grouped into three categories: subjective cognitive impairment, mild cognitive impairment, and mild to moderate dementia. Results. We found an overall tendency for underestimation of time, but no significant differences between groups regarding time estimation. There were significant, but weak, associations between time estimation and severity of cognitive impairment in several domains, with slightly different patterns across groups. Conclusions. Regardless of etiology, the majority of patients underestimated time, which was weakly associated with the severity of cognitive impairment. Global retrospective estimation may be clinically informative, particularly in a minority of extreme cases.

Alcohol abuse and acute behavioural disturbances in a 24-year-old patient

MBD was named after two Italian pathologists who described acute demyelination of the corpus callosum at necropsy in 3 South-Italian male red-wine drinkers. Etiology is unknown. The main pathological features range from demyelination with preserved axon structure, to extensive necrosis with cystic formation and microbleedings. Clinical features are highly variable and include reduced consciousness, unsteady gait, behavioural disturbances, motor defects, seizures and, rarely, interhemispheric disconnection syndromes. Most of these can be seen in much more frequent alcohol-related disorders like Wernicke’s encephalopathy or central pontine myelinolysis, which may not have distinct ocular findings. Recent brain-imaging methods, particularly MRI, disclosed highly specific lesion patterns which, combined with the clinical features, were used to divide MBD in 2 subtypes: type A, characterized by consciousness impairment, extensive T2-weighted hyperintense swelling of the corpus callosum, and bad prognosis; and type B, characterized by behavioural and gait disturbances, restricted ‘‘sandwich-like” T2-weighted hyperintense lesions in the corpus callosum genu or splenium, and a better outcome. MRI also assumes a pivotal role in distinguishing MBD from other diseases, as the lesions affect the central layers of the corpus callosum and

Sporadic Creutzfeldt-Jakob disease causing a 2-years slowly progressive isolated dementia.

A 47-year-old woman was seen for progressive behavioural and cognitive disturbances slowly evolving over a 1-year period. Neuropsychological evaluation disclosed moderate to severe impairment of all cortical functions. Besides this no other clinical abnormality was found. MRI diffusion weighted imaging disclosed hyperintense cortical lesions in a ribbon-like fashion, with restricted diffusivity. EEG showed no periodic sharp waves and CSF examination was normal, including protein 14.3.3. She was heterozygote on codon 129. Her cognitive function continued to decline and she was readmitted for further investigation at the 24th month of disease. Again no ataxia or involuntary movements were observed. MRI disclosed widespread hyperintense lesions over the entire cortex and, for the first time, also caudato-putaminal hyperintensity in T2-weighted images. EEG again failed to show periodic activity. Stereotactic biopsy disclosed moderate spongiform changes, astrocytosis and perivacuolar staining with prion-directed antibodies. Western blot analysis revealed prion type 2 mobility pattern. We discuss the clinical significance of this case: as dementia was the sole finding, and this was slowly-evolving over a 2-year period, MRI findings were the key factor suggesting a prion disease in a woman that otherwise would probably be diagnosed with a primary degenerative dementia.

Neuropsychiatric Profile in Early Versus Late Onset Alzheimer’s Disease:

Background: The aim of this study was to investigate the frequency and severity of neuropsychiatric symptoms (NPS) in patients with early onset Alzheimer’s disease (EAOD) and late onset AD (LOAD). Methods: Patients were selected from a specialized memory outpatient clinic. The Mini-Mental State Examination, the Neuropsychiatric Inventory (NPI), and the Global Deterioration Scale results were analyzed. Results: By comparing EOAD (n = 35) and LOAD (n = 35) patients, no significant differences were found in clinical or demographic variables, matched for sex, education, and disease severity. There were no differences between groups in total NPI frequency or severity scores. The most common NPS were irritability, apathy, anxiety, and depression. We found an association of NPI scores with disease severity and duration, which was more specific in patients with LOAD and was also associated with the presence of delusions and hallucinations. Conclusion: Despite subtle differences, NPS is considered important in the assessment of patients with AD, regardless of the age of onset.