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.

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.

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.

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.

New insights into the brain involvement in patients with Crohn's disease: a voxel-based morphometry study.

BACKGROUND: Crohn's disease (CD) is a chronic intestinal disorder characterized by overproduction of inflammatory cytokines and recurrent abdominal pain. Recently, brain morphological abnormalities in the pain matrix were found in patients with chronic pain disorders including irritable bowel syndrome. To investigate potential structural brain changes associated with CD, we used magnetic resonance imaging (MRI). Furthermore, we tested whether in patients gray matter (GM) volumes correlated with disease duration. METHODS: Eighteen CD patients in remission and 18 healthy controls underwent structural MRI. Voxel-based morphometry (VBM) is a fully automated technique allowing identification of regional differences in the amount of GM enabling an objective analysis of the whole brain between groups of subjects. VBM was used for comparisons and correlation analysis. KEY RESULTS: With respect to controls, CD patients exhibited decreased GM volumes in portion of the frontal cortex and in the anterior midcingulate cortex. Disease duration was negatively correlated with GM volumes of several brain regions including neocortical and limbic areas. CONCLUSIONS & INFERENCES: Crohn's disease is associated with brain morphological changes in cortical and subcortical structures involved in nociception, emotional, and cognitive processes. Our findings provide new insight into the brain involvement in chronic inflammatory bowel disorders.

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.

Early-onset dementia with prolonged occipital seizures: an atypical case of Kufs disease.

OBJECTIVE: Kufs disease is the adult-onset form of neuronal ceroid lipofuscinosis (NCL). Its two clinical phenotypes are type A (progressive myoclonus epilepsy with dementia) and type B (behavioral abnormalities and dementia, associated with pyramidal and extrapyramidal signs). METHODS: We describe the clinical evolution of an atypical case characterized by progressive dementia and focal occipital seizures. RESULTS: A healthy 37-year-old woman began showing memory deficits and behavioral disturbances (apathy, lack of inhibitions, untidiness). After 4 years, she developed rare clusters of tonic-clonic seizures, as well as focal seizures originating from the temporo-occipital regions, clinically associated with visual hallucinations, wandering, and agitation. When she was 44 years old, neuropsychological assessment revealed severe frontotemporal dementia. MRI showed cortical atrophy and, on T2-weighted images, hypointensity of the basal ganglia, and hyperintensity and reduction of the deep white matter. On the basis of these findings, a diagnosis of Kufs disease was hypothesized. A skin biopsy was negative, but electron microscopy examination of a right frontal lobe brain biopsy revealed the presence of typical storage material (fingerprint inclusions). The patient never developed myoclonus or extrapyramidal signs. DISCUSSION: Kufs disease is difficult to diagnose on account of its heterogeneous clinical pattern and pathologic features, and the lack of a specific genetic locus alteration. The neuropsychological pattern and MRI findings observed in patients with early-onset frontotemporal dementia and seizure disorder suggest that Kufs disease should be considered in their differential diagnosis. Extracerebral biopsy can be nondiagnostic, and when alternative diagnoses have been ruled out, cerebral biopsy should be considered.

Apathy and disinhibition in frontotemporal dementia: Insights into their neural correlates.

BACKGROUND: Aberrant social behavior is a defining symptom of frontotemporal dementia (FTD) and may eventually occur in all syndromes composing the FTD spectrum. Two main behavioral abnormalities have been described: apathy and disinhibition, but their neuroanatomical correlates remain underspecified. METHODS: Sixty-two patients with a clinical diagnosis of FTD participated in the study. Voxel-based morphometry of MRI data was performed to explore the association between gray matter loss and severity of the two behavioral profiles as measured by the Apathy and Disinhibition subscales of the Frontal Systems Behavior Scale. RESULTS: Compared with a group of controls, the FTD group showed extensive bilateral atrophy predominantly involving frontal and temporal lobes. Within the FTD group, the severity of apathy correlated with atrophy in the right dorsolateral prefrontal cortex. The severity of disinhibition correlated with atrophy in the right nucleus accumbens, right superior temporal sulcus, and right mediotemporal limbic structures. CONCLUSIONS: Prefrontal and temporal regions are differentially associated with apathy and disinhibition. Our results support the view that successful execution of complex social behaviors relies on the integration of social knowledge and executive functions, represented in the prefrontal cortex, and reward attribution and emotional processing, represented in mesolimbic structures.

Bilateral posterior medullary and cervical stroke: a case report.

Spinal strokes are often localised in the anterior spinal artery territory, whereas an involvement of the posterior spinal arteries (PSA) is uncommon, and usually unilateral. Bilateral PSA stroke is exceptional. A 70-year-old woman, after a mild head trauma, presented with cervical pain, left hypoaesthesia and sensitive ataxia, which then extended to the right hemibody, including face. A Doppler ultrasound showed an only systolic flow signal in the left vertebral artery (VA). MR showed a bilateral infarction extending from the posterior medulla oblongata to C4 and a left hypoplasic VA with lack of visualisation of the V3 segment. This case was peculiar, implying a bilateral stroke in the PSA territory, possibly related to a left VA dissection, and in the presence of a dominant PSA, originating from the hypoplasic VA and of hyposupply of posterior radiculomedullary arteries and anastomoses.

The Frontal Assessment Battery (FAB): normative values in an Italian population sample.

The Frontal Assessment Battery (FAB) is a short cognitive and behavioural six-subtest battery for the bedside screening of a global executive dysfunction; although recently devised, it is already extensively used thanks to its ease of administration and claimed sensitivity. The aim of the present study was to derive Italian normative values from a sample of 364 control subjects (215 women and 149 men) of different ages (mean: 57.4+/-17.9 years; range: 20-94 years) and educational level (mean: 10.4+/-4.3 years; range: 1-17 years); the Mini Mental State Examination (MMSE) was concurrently administered. Multiple linear regression analysis revealed significant effects for age and education whereas gender was not significant; thus, from the derived linear equation, a correction grid for FAB raw scores was built. Based on nonparametric techniques, inferential cut-off scores were subsequently determined and equivalent scores (ES) computed. Test-restest and interrater reliabilities were both satisfactory. Interestingly, MMSE was significantly correlated with FAB raw scores, whereas adjusted scores were not. The present data may improve the accuracy in the use of the FAB both for clinical and research purposes.

Impaired facial emotion recognition in early-onset right mesial temporal lobe epilepsy.

BACKGROUND: Anteromedial temporal lobe regions, particularly the amygdala, participate in the recognition of emotions from facial expressions. The authors studied the ability of facial emotion recognition (ER) in subjects with symptomatic epilepsy, evaluating whether mesial temporal lobe damage is related to an impairment in the recognition of specific emotions and whether the onset of seizures in a critical period of life could prevent the development of ER. METHODS: Groups included patients with temporal lobe epilepsy (TLE) with MRI evidence of mesial temporal sclerosis (MTS) (n = 33); patients with TLE with MRI evidence of temporal lobe lesions other than MTS (n = 30); and patients with extratemporal epilepsy (n = 33). Healthy volunteers (n = 50) served as controls. ER was tested by matching a facial expression with the name of one of the following basic emotions: happiness, sadness, fear, disgust, and anger. A face-matching task was used to control visuoperceptual abilities with face stimuli. RESULTS: No subject showed deficits in the face-matching task. ER was impaired in patients with right MTS, especially for fearful faces. Patients presenting left MTS, right or left temporal lobe lesions other than MTS, or extratemporal seizure foci showed ER performances similar to controls. In all subjects with right TLE, the degree of emotion recognition impairment was related to age at first seizure (febrile or afebrile) and age at epilepsy onset. CONCLUSIONS: Early-onset right-sided mesial temporal lobe epilepsy is the key substrate determining a severe deficit in recognizing emotional facial expressions, especially fear.

Explicit and incidental facial expression processing: an fMRI study.

Considerable evidence indicates that processing facial expression involves both subcortical (amygdala and basal ganglia) and cortical (occipito-temporal, orbitofrontal, and prefrontal cortex) structures. However, the specificity of these regions for single types of emotions and for the cognitive demands of expression processing, is still unclear. This functional magnetic resonance imaging (fMRI) study investigated the neural correlates of incidental and explicit processing of the emotional content of faces expressing either disgust or happiness. Subjects were examined while they were viewing neutral, disgusted, or happy faces. The incidental task required subjects to decide about face gender, the explicit task to decide about face expression. In the control task subjects were requested to detect a white square in a greyscale mosaic stimulus. Results showed that the left inferior frontal cortex and the bilateral occipito-temporal junction responded equally to all face conditions. Several cortical and subcortical regions were modulated by task type, and by facial expression. Right neostriatum and left amygdala were activated when subjects made explicit judgements of disgust, bilateral orbitofrontal cortex when they made judgement of happiness, and right frontal and insular cortex when they made judgements about any emotion.

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.

Researching a differential impairment of frontal functions and explicit memory in early Parkinson's disease.

An impairment at tasks sensitive to frontal lobe damage has been repeatedly reported in Parkinson's disease, but the exact nature of these deficits has not yet been clarified. Similarly, deficits of visuo-spatial functions have been frequently observed, but it is still debated whether verbal and visuo-spatial memory can be differentially affected. In this study we have compared the performance of 20 mild Parkinson's disease patients (I-II Hoehn and Yahr stage) and 18 matched normal controls, at tasks assessing frontal functions and explicit memory. We detected a selective deficit in set shifting and maintaining, without impairment in categorization and set formation. The lack of a selective increase in perseverative errors might indicate that perseverations either measure something different from set shifting or that they do not represent an index sensitive enough to set shifting impairment. Parkinson's disease patients were also significantly impaired at Raven's Progressive Matrices, a task assessing both frontal and visuo-spatial aspects. However, they did not show any differential impairment of visuo-spatial memory. Indeed, despite a trend of lower performance in visuo-spatial learning, memory performance of Parkinson's disease patients was significantly different from that of controls only at a free recall test which involved both verbal and visuo-spatial memory. We suggest the exploration of set shifting and maintaining to detect 'frontal' deficits in mild Parkinson's disease. We argue that Raven's Progressive Matrices is a valuable task for detecting subclinical cognitive deficits in Parkinson's disease, even if it does not show a specific profile of impairment in these patients. According to our results, a differential evaluation of verbal vs. visuo-spatial memory is not necessary in clinical practice, whilst free recall confirms its usefulness to detect subclinical impairments of memory functions.

Selective uppercase dysgraphia with loss of visual imagery of letter forms: a window on the organization of graphomotor patterns.

We report a patient who, after a left parieto-occipital lesion, showed alexia and selective dysgraphia for uppercase letters. He showed preserved oral spelling, associated with handwriting impairment in all written production; spontaneous writing, writing to dictation, real words, pseudowords, and single letters were affected. The great majority of errors were well-formed letter substitutions: most of them were located on the first position of each word, which the patient always wrote in uppercase (as he used to do before his illness). The patient also showed a complete inability to access the visual representation of letters. As demonstrated by a stroke segmentation analysis, letter substitutions followed a rule of graphomotor similarity. We propose that the patient's impairment was at the stage where selection of the specific graphomotor pattern for each letter is made and that the apparent selective disruption of capital case was due to a greater stroke similarity among letters belonging to the same case. We conclude that a visual format is necessary neither for spelling nor for handwriting.

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.

Selective horizontal dysmetropsia following prestriate lesion.

We describe a patient (P.S.) who, following a right prestriate lesion, reported that objects in the left visual field appeared distorted and smaller than those on the right. Other aspects of visual processing were remarkably unaffected. We carried out a series of size comparison tests using simple or complex stimuli and requiring different types of behavioural responses. We found that P.S. significantly underestimated the size of stimuli presented in her left visual field. When comparison tasks involved stimuli placed along the vertical axis or in the right visual field, P.S. performed well. The vertical and horizontal components of size distortion were found to be differentially affected. We conclude that size processing may be dissociated from other aspects of visual processing, such as form or colour processing, and depends critically on part of the occipital, prestriate areas (Brodmann areas 18-19).

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.