Marta Panella

CSF markers in Alzheimer disease patients are not related to the different degree of cognitive impairment

Standard markers in cerebrospinal fluid (CSF), as soluble amyloid beta 1-42 (Abeta1-42) and total tau protein (t-tau), may contribute to dementia subtypes diagnostic accuracy. Yet, their sensitivity to assess the different degree of cognitive deficit is not fully clarified. Our study analyses Abeta1-42 and t-tau CSF levels in different cohorts of Alzheimers disease (AD) patients, distinguished as early AD (mild cognitively impaired subjects recently converted to AD), mild AD (MMSE<23; > or =18), and moderately advanced AD (MMSE<18). The control group was represented by age-matched patients affected by depressive pseudo-dementia. Reduced Abeta1-42 and increased t-tau CSF levels were confirmed as hallmarks of AD at any disease stage. In early AD patients, Abeta1-42 levels were already significantly low, if compared to the control group (336 vs 867 ng/L; p<0.0001). On the contrary, Abeta1-42 levels did not differ between AD subgroups, and in particular between mild to moderate AD. A significant progressive increase of t-tau concentration was found when comparing early AD (269 ng/L) to more advanced AD stages (468 ng/L and 495 ng/L for mild and moderate AD, respectively). Our findings confirm that the impairment of amyloidogenic cascade is an early, even pre-clinical process, but suggest that soluble Abeta1-42 concentration has a negligible correlation with the clinical progression. Conversely, t-tau concentration correlates with the transition towards marked cognitive impairment.

Hashimoto's encephalopathy presenting with musical hallucinosis

Sirs: Neurological complications of thyroid disease are numerous and well known in the case of thyrotoxicosis or myxoedema, while the features of neurological involvement in Hashimoto’s thyroiditis have not been clearly characterised. Hashimoto’s encephalopathy (HE) is a severe and rare disorder, associated with Hashimoto’s thyroiditis, whose pathogenesis [2] is still debated, owing to the lack of specific markers of an autoimmune CNS involvement. At present its diagnosis simply relies on the detection of high titres of thyroid autoantibodies in serum, especially antimicrosomal antibodies, that are typical of Hashimoto’s thyroiditis. According to the literature, HE usually presents as vasculitic type or a diffuse progressive type with dementia, seizures, a psychorganic syndrome or altered consciousness, but atypical cases have been reported [2, 4]. Here we describe the unusual case of a patient presenting after a long lasting episode of complex auditory hallucinosis with musical content, followed by behavioural abnormalities and cerebellar signs. A 65 year-old woman with no history of psychiatric illness, deafness, or drug abuse, presented with an acute episode of auditory hallucinosis characterised by complex musical sounds, which lasted about 36 hours. She described these sounds as an orchestral melody, which occurred suddenly during sleep and persisted without remitting the day after “. . . during that time, it seemed to me to listen to a symphonic piece performed by an orchestra of numerous string instruments . . . the music was of such clarity that I was initially convinced the radio was playing from the next room . . .”. In the following weeks she developed subacute and progressive unsteadiness, slurred speech, writing impairment, reduced appetite with body-weight reduction, irritability and aggressiveness, hypersexuality, disinhibition and inappropriate social behaviour. The neurological examination on admission disclosed a severe dysarthria, severe gait ataxia, Romberg sign, and mild dysmetria. The neuropsychological assessment was normal except for a selective dysgraphia both on spontaneous writing and on dictation. A psychiatric interview revealed no psychopathological elements. General examination was normal, with no palpable goitre. Thyroid stimulating hormones (TSH) and free T3-T4 values were normal. The antimicrosomal antibody titre was increased (920 mUI/ml; normal range 0–10) while antithyreoglobulin antibodies were negative. Routine blood tests, including serum tumour markers, anti-Hu, anti-Yo, anti-Ri antibodies, antinuclear, antiphospholipid and lupus anticoagulants levels were normal. The CSF examination did not show abnormalities. Audiometric investigations including brain stem auditory evoked responses were normal. Repeated EEG disclosed intermittent multifocal theta waves with an asynchronous slowing of the background rhythm. Brain MRI with gadolinium enhancement was normal. Thyroid echography disclosed a multinodular goitre. Thyroid gland scintigraphy was normal. With the hypothesis of an autoimmune-mediated encephalopathy associated with Hashimoto’s thyroiditis the patient was started on regime of steroids for three months (prednisone 50 mg/day p. o.) followed by tapering during two months. A complete remission of psychiatric symptoms was observed by the end of the second month of treatment. Cerebellar signs improved more gradually, and were not detected one month after steroids discontinuation. Laboratory testing repeated three months after treatment onset resulted in a marked reduction of thyroid antimicrosomal antibody titre (170mUI/ml). Three months later the titre was normal. The EEG repeated at the same time was normal. Although visual hallucinations have been previously described as a clinical feature of HE, this appears to be the first report of complex auditory hallucinations with musical content in this clinical entity. Musical hallucinosis represents a particular type of auditory perception of tunes, melodies and sounds without relevant external stimuli, whose unreal nature is recognised by the patient. Transient musical hallucinosis is very rare and has been described in several conditions such as psychiatric disoerders [1], alcoholism [6], various drugs intake [5], sensoryneural deafness [3]. In our case none of these conditions were present, supporting the view that this symptom was part of the clinical presentation of HE. In addition alternative autoimmune disorders were ruled out on the basis of normal level of autoantibodies and general clinical findings. In conclusion, this case further LETTER TO THE EDITORS

Posterior cortical atrophy with unilateral occipito-temporal degeneration.

Sirs: Posterior cortical atrophy (PCA) was first described by Benson in1988 as a variant of Alzheimer’s disease (AD) with atypical clinical presentation [2]. At onset, patients usually complain of visual symptoms such as visual agnosia and show features of Balint’s and Gerstmann’s syndromes or apraxic disorders [1, 3]. Memory and language are impaired later in the course of the disease. Neuroimaging studies have revealed bilateral posterior cortical atrophy and hypoperfusion [3, 5]. We report a case of a woman with clinical features of posterior cortical atrophy due to unilateral occipito-temporal degeneration. A 61-year-old woman came to our observation with a three year history of poor vision and depressed mood. She was referred initially to an ophthalmologist who found no retinal or ocular problems to account for her extreme difficulty in reading and recognizing familiar faces. In particular, she noticed difficulty in reading the whole word but not each single letter, in distinguishing single features of complex visual scenes and in perceiving the relative depth of different visual objects. Later she became unable to dress by herself and to use a fork. Past medical history included only treated hypothyroidism. Her general physical examination was unremarkable. Neurological examination revealed marked restriction of the left visual field. Visual acuity was preserved bilaterally. She had normal pupillary reflexes and her eye movements appeared full except for an impairment of visual fixation (optic ataxia). Colour vision and reaching visual objects in space were intact. She showed a degree of simultanagnosia as she could recognize and identify small object and parts of a large picture but she had difficulty in perceiving together the parts of the scene. She had also an impairment in judging distances between visualised objects. Neuropsychological assessment revealed mild temporo-spatial disorientation. Her MMSE score was 18. Only verbal formal neuropsychological tests were administered because of her severe visual and perceptual disturbances. The patient obtained normal scores in a neuropsychological test battery evaluating short and long-term memory (Rey Word List, Immediate and Delayed Recall; Digit Span; Free Recall of a prose passage); mental arithmetic was very poor; language evaluation (Boston Naming Test, Phrase Construction) demonstrated mild nominal aphasia; executive functions (Verbal Fluency) were preserved. Supplementary testing revealed that she had poor recognition of famous faces and visual agnosia (Visual Object and Space Perception Battery – VOSP) [8]. Although the patient’s writing was normal, her reading was impaired. She was only able to read simple words using a letter-by-letter strategy. MRI revealed a marked enlargement of the occipital horn of the right lateral ventricle with severe atrophy of the right occipito-temporal cortex (Fig. 1A). HMPAOSPECT demonstrated the absence of perfusion in the right temporooccipital areas and a relative right posterior parietal hypometabolism sparing the calcarine cortex (Fig. 1B). CSF examination was normal while levels of amyloid-beta 1–42 were significantly low (44 pg/ml), supporting the diagnosis of AD. Total tau and phosphorylated tau 181 were normal [10]. EEG showed asymmetric slowing over the right posterior regions. In the recently described PCA, a focal variant of AD, two main clinical syndromes can be distinguished reflecting the prominent involvement of the occipitotemporal (ventral) or biparietal (dorsal) cortical areas [9]. The ventral (“what”) visual processing stream is important for object, face and written word recognition while the dorsal (“where”) stream subserves object location, visually guided motor movements and motor planning [6]. Our patient showed clinical signs of disruption of both pathways since she presented elements of Balint’s syndrome (optic apraxia, simultanagnosia), visual agnosia, prosopagnosia, dressing apraxia, dyscalculia and letter-by-letter alexia. This clinical spectrum of visual and perceptual symptoms suggested a wide bilateral posterior pathology. Surprisingly, we found only a marked unilateral cortical atrophy and a wider reduced metabolism of the right temporo-parietooccipital region, probably due to earlier functional impairment that had been detected by SPECT imaging. Mendez and colleagues, in a recent study, described 15 PCA patients who all showed evidence of bilateral dysfunction as well as bilateral occipito-parietal hypoperfusion at the time of presentation [5]. Moreover recent findings reported that PCA patients show selective hyLETTER TO THE EDITORS

Mechanical thrombectomy of acute ischemic stroke with a new intermediate aspiration catheter: preliminary results

Background and purpose To report clinical and procedural outcomes of acute ischemic stroke patients after endovascular treatment with the new thromboaspiration catheter AXS Catalyst 6. Methods Patients with anterior and posterior circulation stroke were selected. Successful reperfusion defined as a Thrombolysis in Cerebral Infarction (TICI) score ≥2 b and 3-month functional independence defined as a modified Rankin Scale (mRS) ≤2 were the main efficacy outcomes. Symptomatic intracranial hemorrhage and mortality were the main safety outcomes. Results 107 patients were suitable for analysis. Mean age was 73.18±12.62 year and median baseline NIHSS was 17 (range: 3–32). The most frequent site of occlusion was the middle cerebral artery (MCA) (60.7%). 76.6% of patients were treated with AXS Catalyst 6 alone without the need for rescue devices or thromboaspiration catheters. Successful reperfusion was achieved in 84.1%, functional independence in 47.6%, symptomatic intracranial hemorrhage occurred in 3.7%, and mortality in 21.4%. Conclusions Endovascular treatment with AXS Catalyst 6 proved to be safe, technically feasible, and effective. Comparison analyses with other devices for mechanical thrombectomy are needed.

CT Angiography ASPECTS Predicts Outcome Much Better Than Noncontrast CT in Patients with Stroke Treated Endovascularly

BACKGROUND AND PURPOSE: Noncontrast CT ASPECTS has been investigated as a predictor of outcome in patients with acute ischemic stroke. Our purpose was to investigate whether CTA source images are a better predictor of clinical and radiologic outcomes than NCCT ASPECTS in candidates for endovascular stroke therapy. MATERIALS AND METHODS: CT scans of patients (n = 124) were independently evaluated by 2 readers for baseline NCCT and CTA source image ASPECTS and for follow-up ASPECTS. An mRS of ≤2 at 3 months was considered a favorable outcome. Receiver operating characteristic curve analysis was used to assess the ability of NCCT and CTA source image ASPECTS to identify patients with favorable outcomes. A stepwise multiple regression analysis was performed to find independent predictors of outcome. RESULTS: Baseline CTA source image ASPECTS correlated better than NCCT ASPECTS with follow-up ASPECTS (r = 0.76 versus r = 0.51; P for comparison of the 2 coefficients < .001). Receiver operating characteristic curve analysis showed that baseline CTA source image ASPECTS compared with NCCT ASPECTS can better identify patients with favorable outcome (CTA source image area under the curve = 0.83; 95% CI, 0.76–0.91; NCCT area under the curve = 0.67; 95% CI, 0.58–0.77; P < .001). Finally, the stepwise regression analysis showed that lower age, good recanalization, lower time to recanalization, and good baseline CTA source image ASPECTS, not NCCT ASPECTS, were independent predictors of favorable outcome. CONCLUSIONS: CTA source image ASPECTS predicts outcome better than NCCT ASPECTS; this finding suggests CTA rather than NCCT as a main step in the decision-making process for patients with acute ischemic stroke.

Pretreatment predictors of malignant evolution in patients with ischemic stroke undergoing mechanical thrombectomy

Background Few data exist on malignant middle cerebral artery infarction (MMI) among patients with acute ischemic stroke (AIS) after endovascular treatment (ET). Numerous predictors of MMI evolution have been proposed, but a comprehensive research of patients undergoing ET has never been performed. Our purpose was to find a practical model to determine robust predictors of MMI in patients undergoing ET. Methods Patients from a prospective single-center database with AIS secondary to large intracranial vessel occlusion of the anterior circulation, treated with ET, were retrospectively analyzed. We investigated demographic, clinical, and radiological data. Multivariate regression analysis was used to identify clinical and imaging predictors of MMI. Results 98 patients were included in the analysis, 35 of whom developed MMI (35.7%). No differences in the rate of successful reperfusion and time from stroke onset to reperfusion were found between the MMI and non-MMI groups. The following parameters were identified as independent predictors of MMI: systolic blood pressure (SBP) on admission (p=0.008), blood glucose (BG) on admission (p=0.024), and the CTangiography (CTA) Alberta Stroke Program Early CT Score (ASPECTS) (p=0.001). A scoreof ≤5 in CTA ASPECTS was the best cut-off to predict MMI evolution (sensitivity 46%; specificity 97%; positive predictive value 78%; negative predictive value 65%). Conclusions in our study a clinical and radiological features-based model was strongly predictive of MMI evolution in AIS. High SBP and BG on admission and, especially, a CTA ASPECTS ≤5 may help to make decisions quickly, regardless of time to treatment and successful reperfusion.