Safety and outcomes of routine endovascular thrombectomy in large artery occlusion recorded in the SITS Register: An observational study.

BACKGROUND AND OBJECTIVE: We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS-International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies. METHODS: We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014-2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST. RESULTS: Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44-47), 46.0% (42-50), 38% (35-41) and 37% (35-41), respectively; death was 19.2% (19-21), 15.3% (12.7-18.4), 29.2% (27-32) and 28.6% (27-31); and SICH was 3.6% (3-4), 4.4% (3.0-6.4), 5.8% (4.7-7.1) and not available. CONCLUSION: Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies.

Intravenous thrombolysis in stroke mimics: results from the SITS International Stroke Thrombolysis Register.

BACKGROUND AND PURPOSE: Patients with stroke mimics (SM), i.e. conditions with stroke-like symptoms, may risk harm if treated with intravenous thrombolysis (IVT). Current guidelines state low risk of intracerebral hemorrhage based on studies comprising a total of <400 SM cases. We aimed to compare safety and outcomes following IVT between patients with acute ischaemic stroke and mimicking conditions. METHODS: We included IVT-treated ischaemic stroke patients in the SITS International Stroke Thrombolysis Register 2003-2017, examined with magnetic resonance imaging 22-36 h after treatment. Outcomes were parenchymal hematoma (PH) after treatment, symptomatic intracerebral hemorrhage (SICH) per Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST), Second European Co-operative Stroke Study (ECASS II) and National Institutes of Neurological Disorders and Stroke Study (NINDS) criteria, death and modified Rankin Scale score (mRS) at 3 months. RESULTS: Of 10 436 patients, 429 mimics (4.1%) were identified. The most common types were functional (30.8%), migraine (17.5%) and seizure (14.2%). Patients with mimics had fewer cerebrovascular risk factors and lower median National Institutes of Health Stroke Scale score [7 (interquartile range, 5-10) vs. 8 (5-14), P < 0.001]. Among mimics versus stroke patients, PH was seen in 1.2% vs. 5.1% (P < 0.001), SICH NINDS in 0.5% vs. 3.9% (P < 0.001), SICH ECASS II in 0.2% vs. 2.1% (P = 0.007) and SICH SITS-MOST in 0% vs. 0.5% (P = 0.28). Modified Rankin Scale score 0-1 at 3 months was present in 84.1% vs. 57.7% (P < 0.001) and death within 3 months in 2.6% vs. 5.4% (P = 0.028) of mimics and stroke patients, respectively. CONCLUSIONS: This large observational study indicated that PH and SICH following IVT in patients with SM are uncommon.

Primary progressive multiple sclerosis and generalized myasthenia gravis: an uncommon association.

The co-occurrence of myasthenia gravis (MG) and multiple sclerosis (MS) is rare, and in all the described cases MS had a relapsing-remitting course and the diseases had a benign clinical evolution. We describe herewith a patient with primary progressive MS (PPMS) and generalized MG with severe clinical course. This is the first report on a case of PPMS associated to MG. Studies on the histology and pathogenesis show that neurodegeneration is predominant over inflammation in PPMS, even if cellular and humoral immune-mediated mechanisms are thought to maintain a crucial importance in the development and progression of this form of disease. In the present case, the detection of cerebrospinal fluid IgM oligoclonal bands support the hypothesis of a possible role of antibody-mediated immunity in PPMS and suggest that humoral immunity may take part in the concomitant development of both MS and MG.

A challenging diagnosis of reversible "vascular" dementia: Cerebral amyloid angiopathy-related inflammation.

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare and treatable variant of CAA likely due to an autoimmune response directed toward beta-amyloid deposits. Cognitive and behavioral manifestations are the most common symptoms, followed by focal neurological signs, headache and seizures, associated with characteristics neuroradiological features on brain magnetic resonance imaging (MRI). We describe the clinical course, radiological features and therapeutic approach of two patients with probable CAA-ri with the aim of emphasizing the importance of an early diagnosis of this potentially reversible disease in different neurological settings, such as memory clinics and stroke units.

Stress and brain functional changes in patients with Crohn's disease: A functional magnetic resonance imaging study.

BACKGROUND: In Crohn's disease (CD) patients, stress is believed to influence symptoms generation. Stress may act via central nervous system pathways to affect visceral sensitivity and motility thus exacerbating gastrointestinal symptoms. The neural substrate underpinning these mechanisms needs to be investigated in CD. We conducted an explorative functional magnetic resonance imaging (fMRI) study in order to investigate potential differences in the brain stress response in CD patients compared to controls. METHODS: 17 CD patients and 17 healthy controls underwent a fMRI scan while performing a stressful task consisting in a Stroop color-word interference task designed to induce mental stress in the fMRI environment. KEY RESULTS: Compared to controls, in CD patients the stress task elicited greater blood oxygen level dependent (BOLD) signals in the midcingulate cortex (MCC). CONCLUSIONS & INFERENCES: The MCC integrate "high" emotional processes with afferent sensory information ascending from the gut. In light of these integrative functions, the stress-evoked MCC hyperactivity in CD patients might represent a plausible neural substrate for the association between stress and symptomatic disease. The MCC dysfunction might be involved in mechanisms of central disinhibition of nociceptive inputs leading to amplify the visceral sensitivity. Finally, the stress-evoked MCC hyperactivity might affect the regulation of intestinal motility resulting in exacerbation of disease symptoms and the autonomic and neuroendocrine regulation of inflammation resulting in enhanced inflammatory activity.

Imitating gestures. A quantitative approach to ideomotor apraxia.

The ability to carry out movements on imitation was assessed with a 24-item test in uniterally hemisphere-damaged patients. On the basis of a cutoff score derived from the performances of 100 control patients, 20% of the right brain-damaged patients were calssified as apraxic. Most right brain-damaged patients were only mildly defective, but a few showed a striking impairment. In left brain-damaged patients apraxia was not only more frequent, but also much more severe and was nearly always associated with aphasia. However, the correlation between the motor and the language disorder was not particularly high, and the link between the two symptoms was thought to be dependent on the contiguity of the underlying nervous structures.

Implicit and explicit memory in patients with Parkinson's disease with and without dementia.

OBJECTIVE: To study explicit and implicit memory processes in patients with Parkinson's disease. DESIGN: Case-control design. All subjects were given a neuropsychological test battery, and the test scores were compared among the groups. SETTING: Government-funded research facility. All subjects were examined as outpatients. PATIENTS: We tested nondemented (n = 13) and demented (n = 5) patients with Parkinson's disease and normal controls (n = 12) matched for age, gender, and educational level. MAIN OUTCOME MEASURES: Memory for verbal and pictorial stimuli under both explicit and implicit retrieval conditions. RESULTS: Both nondemented and demented patients with Parkinson's disease exhibited impairment on tests of explicit memory. Their impairment could be graded based on the level of effort required by the task: impaired free recall in nondemented patients and impaired free recall, cued recall, and recognition in demented patients. By contrast, neither group showed evidence of impairment on automatic (modality monitoring and word frequency estimation) or implicit (word and picture fragment identification) memory tasks. Correlation analyses did not support any association between the effortful memory deficits and neurologic variables, mood, or performance on executive function tests. CONCLUSIONS: Memory deficits in patients with Parkinson's disease primarily involve the conscious, effortful strategic aspects of searching long-term memory.

Induction of visual extinction by rapid-rate transcranial magnetic stimulation of parietal lobe.

We used repetitive, rapid-rate transcranial magnetic stimulation (rTMS) for the noninvasive study of visual attention in humans. Six right-handed volunteers completed eight blocks of 20 single- and 10 double-visual-stimulus trials. The visual stimulus was a single asterisk on the right or left side of a computer screen or two asterisks presented simultaneously. The subject had to respond to the stimulus by pressing the right or left response key or both keys simultaneously. During six of the blocks, we applied focal rTMS in trains of five pulses at 25 Hz and 115% of the subject's motor threshold intensity to scalp positions O1, O2, P3, P4, T5, or T6. Occipital rTMS led to a large number of misses of the contralateral asterisk regardless of whether a single or double stimulus was presented. Parietal rTMS did not induce misses of single stimuli but led to a large number of misses of the contralateral asterisk in the double-stimulus condition. The effects of temporal rTMS were inconsistent. We conclude that rTMS to the occipital lobe causes a sensory detection block, whereas rTMS to the parietal lobe can induce selective extinction of contralateral visual stimuli during a simultaneous double stimulus.

Perceptual timing in cerebellar degeneration.

This study examined time perception in 12 patients with cerebellar degeneration (CD) and in 13 normal controls (NC). We used a time bisection procedure with four interval conditions (100-900 msec; 8-32 sec; 100-600 msec; 100-325 msec). Each subject's bisection point, discrimination ability (the Weber ratio) and precision (the inverse of the proportion of unexplained variance) was calculated for each condition. CD patients' performance on the 100-900 msec time bisection condition suggested a possible time discrimination deficit, which was confirmed with intervals in the range of 100-600 msec. Time discrimination was normal on the 100-325 msec condition and impaired on the 8-32 sec bisection task. However, when discriminating long intervals, CD patients also showed a precision deficit, which points to impaired sustained attention and/or decision processes. Our findings corroborate the view that cerebellar timing processes are not limited to the motor system but are also used in perceptual computations.

Relationships between speed, accuracy of performance and hemispheric superiorities for visuo-spatial pattern processing in the two sexes.

The aim of this study was to investigate the relationship between visual field differences in tachistoscopic recognition of visuo-spatial patterns and overall proficiency in the two sexes. The results demonstrated a left visual field advantage in males but not in females. A female subgroup showed opposite rather than lacking visual field superiorities without affecting speed and accuracy of performance. These data warn against explaining differences in performance in the two sexes in terms of different hemispheric asymmetries.

Frequency and recognition judgement by young and elderly adults.

The aim of this study was to compare the performance of young and elderly subjects at two different memory tasks (frequency judgement and word recognition) under two retrieval conditions (forced and unforced choice) in order to determine the source of any incidental age-related memory deficit. Fifty young subjects (aged from 15 to 35 yr) and 50 elderly subjects (aged from 60 to 85) participated in this study. The results showed a significant difference between age groups at word recognition independent of retrieval condition, while frequency judgement was found significantly impaired in elderly as compared with young subjects only when an unforced choice procedure was required. It is suggested that age related memory impairment is not dependent on the nature of the task, but rather to the amount of retrieval information which is given to the subjects.

Kinematic analysis of the reach to grasp movement in Parkinson's and Huntington's disease subjects.

This experiment investigates the kinematic characteristics of the reach to grasp movement of Parkinson's and Huntington's disease subjects under two different experimental conditions. In the first condition subjects were required to perform the movement at a normal speed, while in the second condition they were required to perform the movement as fast as possible. Results showed that the kinematic parameterization of movement in Parkinson's disease subjects did not differ from that of age-matched control subjects for both the normal and the fast condition. However, the performances of Huntington's disease subjects appeared to be different when compared to the other two groups. Differences were mainly related to Huntington's disease patients' inability to properly define the temporal features of the movements.

Precision and accuracy of subjective time estimation in different memory disorders.

The aim of this study was to evaluate how different memory disorders affect subjective time durations. For this purpose we studied prospective time estimations in 4 amnesic (A) and in 15 Alzheimer's disease (AD) patients, and compared their performance with that of 5 matched young normal controls (YC) and 15 elderly subjects (EC). For the short-time durations we asked the subject to repeatedly reproduce a standard interval of 1 s. To test how subjects evaluated longer time durations, we choose a verbal estimation procedure. The subjects' task was to read either 5, 10, 20, or 40 digits appearing one at a time, while concurrently keeping the rhythm of 1 key press per second. At the end of each sequence, subjects had to judge the elapsed time from the beginning of the trial. Results showed that amnesics can correctly reproduce 1-s intervals. However, their accuracy of verbal estimates of longer durations was severely impaired. AD patients showed increased variability on repeated reproduction of 1-s intervals and were both inaccurate and imprecise in their verbal estimate of longer durations. Using the framework of the Scalar Timing Model, we conclude that amnesic patients exhibit a deficit in encoding and storing the current time for intervals that exceed their short-term memory range, while AD patients show a pattern of deficit that is explained by a more widespread involvement of both the clock, the memory, and the decisional mechanisms.

Time perception in a neglected space.

We have studied the distortion of perceived time in a patient with left neglect. This patient consistently over-estimated the duration of stimuli in the neglected space. Overestimation was observed both with an interval comparison (300/700 ms) and with a time production (1 s) paradigm. We suggest that encoding duration in the hundreds of milliseconds range is a process based on an internal clock mechanism. The functioning of that clock varies as a function of the processing load.

Induction of a recall deficit by rapid-rate transcranial magnetic stimulation.

We used rapid-rate, repetitive transcranial magnetic stimulation (rTMS) for the noninvasive study of verbal recall. Five right-handed normal subjects were studied. Recall followed immediately after presentation of a 12-word list. Focal rTMS was applied with a figure eight coil in trains of 500 ms duration to F7, F8, T5, T6, P3, P4, or O1, O2 at latencies of 0, 250, 500, or 1000 ms during word list presentation. Recall was consistently significantly diminished only after left mid-temporal and bilateral dorsofrontal rTMS at both 0 and 250 ms latencies. We conclude that rTMS may be useful as a non-invasive tool for the study of verbal memory processes.

Where the brain appreciates the moral of a story.

To identify the distributed brain regions used for appreciating the grammatical, semantic and thematic aspects of a story, regional cerebral blood flow was measured with positron emission tomography in nine normal volunteers during the reading of Aesop's fables. In four conditions, subjects had to monitor the fables for font changes, grammatical errors, a semantic feature associated with a fable character, and the moral of the fable. Both right and left prefrontal cortices were consistently, but selectively, activated across the grammatical, semantic, and moral conditions. In particular, appreciating the moral of a story required activating a distributed set of brain regions in the right hemisphere which included the temporal and prefrontal cortices. These findings emphasize that story processing engages a widely distributed network of brain regions, a subset of which become preferentially active during the processing of a specific aspect of the text.

Bilateral representation of sequential finger movements in human cortical areas.

The spatial distribution of cortical neural clusters activated during movement of either hand ('bilateral' population), or only of one hand, was investigated in healthy right-handed volunteers performing a sequential finger opposition task, using echo-planar functional magnetic resonance imaging. 'Bilateral' clusters were found in the mesial premotor, perirolandic and adjacent lateral premotor cortex of the two hemispheres, and in the left superior parietal lobule. In the precentral gyrus, their spatial extent was larger on the left hemisphere. Clusters activated exclusively during contralateral finger movements were equally distributed in the left and right perirolandic cortex. No cluster activated exclusively during ipsilateral finger movements was detected. These findings support a role of the motor/lateral premotor cortex of the dominant hemisphere in bilateral motor control.

The Apolipoprotein E genotype in patients affected by syndromes with focal cortical atrophy.

The role of the Apolipoprotein E (APOE) alleles in syndromes associated with focal cerebral atrophy (fronto-temporal dementia, primary progressive aphasia, corticobasal degeneration) is still controversial. We studied the APOE allele distribution in 39 patients with clinically diagnosed syndromes associated with focal cerebral atrophy (FCA), in 50 patients with early-onset probable Alzheimer's disease (EOAD), and in 60 patients with late-onset probable AD (LOAD). The APOE genotype was determined from a blood sample, using polymerase chain reaction and restriction enzyme digestion. The APOE epsilon4 allele frequency was significantly higher in the EOAD (21.0%) and LOAD (33.3%) groups, but not in the FCA group (5.1%), as compared with controls. In our population, the epsilon2 allele frequency was significantly higher in patients with FCA (12.8%) than in controls (4.8%). These results show that the APOE epsilon4 allele is not a risk factor for syndromes associated with FCA. The potential role of the epsilon2 allele in these syndromes needs further investigation.

Recognition of random shapes in unilateral brain damaged patients: a reappraisal.

The performance of unilateral brain-damaged patients on recognition of random shapes was investigated by means of two different experiments. In experiment I interitem similarity and number of response-choice alternatives were varied to evaluate their possible influence on the subjects' performance. In experiment II stimulus exposure time was varied, In both experiments left brain-damaged patients with visual field defect obtained lower scores than control subjects. Right brain-damaged patients with visual field defect obtained scores significantly lower than controls only in the brief exposure condition.