CADASIL in Greece: Mutational spectrum and clinical characteristics based on a systematic review and pooled analysis of published cases.

BACKGROUND: Differences have been noted in the clinical presentation and mutational spectrum of CADASIL among various geographical areas. The aim of the present study was to investigate the mode of clinical presentation and genetic mutations reported in Greece. METHODS: After a systematic literature search, we performed a pooled analysis of all published CADASIL cases from Greece. RESULTS: We identified 14 studies that reported data from 14 families comprising 54 patients. Migraine with aura was reported in 39%, ischemic cerebrovascular diseases in 68%, behavioral-psychiatric symptoms in 47% and cognitive decline in 60% of the patients. The mean (±SD) age of onset for migraine with aura, ischemic cerebrovascular diseases, behavioral-psychiatric symptoms and cognitive decline was 26.2 ± 8.7, 49.3 ± 14.6, 47.9 ± 9.4 and 42.9 ± 10.3, respectively; the mean age at disease onset and death was 34.6 ± 12.1 and 60.2 ± 11.2 years. With respect to reported mutations, mutations in exon 4 were the most frequently reported (61.5% of all families), with the R169C mutation being the most common (30.8% of all families and 50% of exon 4 mutations), followed by R182C mutation (15.4% of all families and 25% of exon 4 mutations). CONCLUSIONS: The clinical presentation of CADASIL in Greece is in accordance with the phenotype encountered in Caucasian populations, but differs from the Asian phenotype, which is characterized by a lower prevalence of migraine and psychiatric symptoms. The genotype of Greek CADASIL pedigrees is similar to that of British pedigrees, exhibiting a high prevalence of exon 4 mutations, but differs from Italian and Asian populations, where mutations in exon 11 are frequently encountered.

A Comparative Analysis of White Matter Structural Networks on SCLC Patients After Chemotherapy.

Previous sMRI, DTI and rs-fMRI studies in small cell lung cancer (SCLC) patients have reported that patients after chemotherapy had gray and white matter structural alterations along with functional deficits. Nonetheless, few are known regarding the potential alterations in the topological organization of the WM structural network in SCLC patients after chemotherapy. In this context, the scope of the present study is to evaluate the WM structural network of 20 SCLC patients after chemotherapy and to 14 healthy controls, by applying a combination of DTI with graph theory. The results revealed that both SCLC and healthy controls groups demonstrated small world properties. The SCLC patients had decreased values in the clustering coefficient, local efficiency and degree metrics as well as increased shortest path length when compared to the healthy controls. Moreover, the two groups reported different topological reorganization of hub distribution. Lastly, the SCLC patients exhibited significantly decreased structural connectivity in comparison to the healthy group. These results underline that the topological organization of the WM structural network in SCLC patients was disrupted and hence constitute new vital information regarding the effects that chemotherapy and cancer may have in the patients' brain at network level.

Demyelination with autoimmune features: a distinct clinical entity? Results from a longitudinal cohort.

OBJECTIVE: CNS demyelinating syndromes occurring in the context of SLE may represent a manifestation of neuropsychiatric lupus, or an overlap of SLE and multiple sclerosis (MS). We evaluated prospectively patients presenting with demyelinating syndrome for clinical and serological evidence of SLE and characterized the evolution of their clinical syndrome to a defined disease. METHODS: Patients with CNS demyelinating syndromes not fulfilling the criteria for MS were evaluated in a rheumatology unit for features of SLE and followed longitudinally (enrolment period 2016-20). Clinical, laboratory and neuroimaging data were recorded at every visit, following multidisciplinary evaluation. At end of follow-up, patients were assessed for their final neurological and rheumatological diagnosis, and classified accordingly. RESULTS: A total of 79 patients were included in the study [91.1% female, mean (s.d.) age at first demyelinating episode 38.4 (10.3) years, median (interquartile range) observation period 39 (57) months]. At last follow-up, 38 patients (48.1%) had evolved into MS. Of the remaining patients, 7 (17.1%) had SLE, while 34 (82.9%) had features of systemic autoimmunity without fulfilling classification criteria for SLE. The most common rheumatological features of these patients were inflammatory arthritis (73.5%), acute cutaneous lupus (47.1%) and positive ANA (72.1%). Importantly, these patients were less likely to have elevated IgG index (odds ratio 0.11, 95% CI 0.04, 0.32) and positive oligoclonal bands (odds ratio 0.21, 95% CI 0.08, 0.55). CONCLUSION: A significant number of patients with demyelination do not fulfill criteria for either MS or SLE at follow-up. These patients exhibit lupus-like autoimmune features and may represent a distinct entity, 'demyelination with autoimmune features'.

Evolving Causes of Rapidly Progressive Dementia: A 5-Year Comparative Study.

BACKGROUND: Rapidly progressive dementia (RPD) is a clinical syndrome developing in <1 to 2 years. Recent progress in RPD evaluation is significant, so RPD's prevalence may change over time. The aim of our new case series was to estimate the relative frequency of RPDs' causative entities, considering the recent advances in RPDs' diagnosis, and compare the results with those of our previous report. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 47 patients who were referred to Attikon University Hospital during a 5-year period for a suspected RPD. RESULTS: Neurodegenerative diseases were the most frequent causes (38%), followed by prion disease (19%) and autoimmune encephalopathy (AE, 17%). AE cases were by far more common than in our previous report, while other than AE secondary causes were significantly decreased. Mean time to dementia was 9 months in neurodegenerative diseases and 5 months in non-neurodegenerative. Main clinical findings across all patients were memory impairment (66%) and behavioral-emotional disturbances (48%). CONCLUSIONS: Neurodegenerative diseases are common causes of RPD and have a slower evolution than non-neurodegenerative. Diagnostic novelties enabled the recognition of AE, whereas more common secondary causes are probably now diagnosed in primary settings since the recognition of RPD as distinct clinical entity is continually increasing.

Chemotherapy-Induced Brain Effects in Small-Cell Lung Cancer Patients: A Multimodal MRI Study.

The golden standard of treating Small Cell Lung Cancer (SCLC) entails application of platinum-based chemotherapy, is often accompanied by Prophylactic Cranial Irradiation (PCI), which have been linked to neurotoxic side-effects in cognitive functions. The related existing neuroimaging research mainly focuses on the effect of PCI treatment in life quality and expectancy, while little is known regarding the distinct adverse effects of chemotherapy. In this context, a multimodal MRI analysis based on structural and functional brain data is proposed in order to evaluate chemotherapy-specific effects on SCLC patients. Data from 20 patients (after chemotherapy and before PCI) and 14 healthy controls who underwent structural MRI, DTI and resting state fMRI were selected in this study. From a structural aspect, the proposed analysis included volumetry and thickness measurements on structural MRI data for assessing gray matter dissimilarities, as well as deterministic tractography and Tract-Based Spatial Statistics (TBSS) on DTI data, aiming to investigate potential white matter abnormalities. Functional data were also processed on the basis of connectivity analysis, evaluating brain network parameters to identify potential manifestation of functional inconsistencies. By comparing patients to healthy controls, the obtained results revealed statistically significant differences, with the patients' brains presenting reduced volumetry/thickness and fractional anisotropy values, accompanied by prominent differences in functional connectivity measurements. All above mentioned findings were observed in patients that underwent chemotherapy.

Demyelinating Syndromes in Systemic Lupus Erythematosus: Data From the "Attikon" Lupus Cohort.

Background: The demyelinating syndromes of the central nervous system (CNS) that occur in the context of systemic lupus erythematosus (SLE) may represent a manifestation of neuropsychiatric lupus (NPSLE) or an overlap of SLE and multiple sclerosis (MS). The differential diagnosis between the two entities has important clinical implications because the therapeutic management differs. Objectives: To characterize CNS demyelinating syndromes in a large SLE cohort as neuropsychiatric SLE (NPSLE) or SLE-MS overlap using a multidisciplinary approach and existing diagnostic (for MS) and classification criteria (for SLE). Methods: Patients from the "Attikon" lupus cohort (n = 707) were evaluated for demyelinating syndromes. Clinical, laboratory, and neuroimaging data were recorded for each patient. Following multidisciplinary evaluation and application of criteria, the demyelinating syndrome was attributed to either SLE or MS. Patients with transverse myelitis were not included in this study. Results: We identified 26 patients with demyelinating syndromes (3.7%). Of them, 12 were diagnosed as primary SLE-demyelination (46.2%) and 14 as overlap SLE-MS (53.8%). The two groups did not differ with respect to rheumatologic and neurologic manifestations or autoantibodies. SLE patients with demyelination manifested mild extra-CNS disease mainly involving joints and skin, while severe non-CNS manifestations were rare. However, these patients were less likely to have elevated IgG index (OR 0.055 95% CI: 0.008-0.40) and positive oligoclonal bands (OR 0.09 95% CI: 0.014-0.56), as well as brain lesions in the spinal cord, infratentorial, periventricular, and juxtacortical regions. A single brain region was affected in 9 patients with SLE-demyelination (75%), while all patients with MS-SLE had multiple affected brain regions. MS-SLE overlap was associated with an increased likelihood of neurologic relapses (OR 18.2, 95% CI: 1.76-188), while SLE-demyelination patients were less likely to exhibit neurological deficits (EDSS >0) at the last follow-up visit (50 vs. 78.6% in SLE-MS, respectively). Conclusions: Demyelination in the context of SLE follows a more benign course compared to a frank SLE-MS overlap. Extension of follow-up will ascertain whether patients with SLE-demyelination evolve to MS, or this is a bona fide NPSLE syndrome.

Guillain-Barré syndrome and fulminant encephalomyelitis following Ad26.COV2.S vaccination: double jeopardy.

This correspondence comments on a published article presenting a case of rhombencephalitis following SARS-CoV-2-vaccination with the mRNA vaccine BNT162b2 (Pfizer/BioNTech). We also present the case of a 47-year-old man who developed Guillain-Barré-syndrome and a fulminant encephalomyelitis 28 days after immunization with Ad26.COV2.S (Janssen/Johnson & Johnson). Based on the presented cases, we underscore the importance of clinical awareness for early recognition of overlapping neuroimmunological syndromes following vaccination against SARS-CoV-2. Additionally, we propose that that role of autoantibodies against angiotensin-converting enzyme 2 (ACE2) and the cell-surface receptor neuropilin-1, which mediate neurological manifestations of SARS-CoV-2, merit further investigation in patients presenting with neurological disorders following vaccination against SARS-CoV-2.

Stopping "transient ischemic attacks" by antiplatelet withdrawal.

INTRODUCTION: Transient ischemic attack (TIA) is considered to be an important risk factor for the development of ischemic stroke and requires complete etiopathogenic evaluation and prompt initiation of secondary prevention treatment. In addition, an accurate differential diagnosis should be performed in order to exclude other disorders mimicking TIA. METHODS: In this case report, we describe the clinical and neuroimaging evaluation and the differential diagnosis of a patient with suspected crescendo TIAs. RESULTS: A 79-year-old man presented with recurrent episodes of right-sided numbness over the past 7 months, despite different single and dual antiplatelet therapies that were sequentially prescribed for suspected TIAs. Brain MRI revealed cortical superficial siderosis, symmetrical periventricular leukoencephalopathy and enlarged perivascular spaces. Cerebral amyloid angiopathy was considered in the differential diagnosis of the patient. Antiplatelet withdrawal was recommended and led to complete remission of the patient's transient focal neurological episodes (TFNE) that were initially misdiagnosed as TIAs. DISCUSSION: Cortical superficial siderosis has been implicated as a key neuroimaging feature of cerebral amyloid angiopathy, a diagnosis which can be supported by the additional radiological findings of symmetrical white matter hyperintensities and enlarged perivascular spaces. Antiplatelet treatment in patients with cortical superficial siderosis may increase the frequency and severity of TFNE, while it increases exponentially the risk of intracerebral hemorrhage. The present case highlights that recognition of cortical superficial siderosis is crucial in the management of patients presenting with transient focal neurological symptoms that can be misdiagnosed as recurrent TIAs.

COVID-19: Neuroimaging Features of a Pandemic.

BACKGROUND AND PURPOSE: The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is occasionally associated with manifold diseases of the central nervous system (CNS). We sought to present the neuroimaging features of such CNS involvement. In addition, we sought to identify typical neuroimaging patterns that could indicate possible COVID-19-associated neurological manifestations. METHODS: In this systematic literature review, typical neuroimaging features of cerebrovascular diseases and inflammatory processes associated with COVID-19 were analyzed. Reports presenting individual patient data were included in further quantitative analysis with descriptive statistics. RESULTS: We identified 115 studies reporting a total of 954 COVID-19 patients with associated neurological manifestations and neuroimaging alterations. A total of 95 (82.6%) of the identified studies were single case reports or case series, whereas 660 (69.2%) of the reported cases included individual information and were thus included in descriptive statistical analysis. Ischemia with neuroimaging patterns of large vessel occlusion event was revealed in 59.9% of ischemic stroke patients, whereas 69.2% of patients with intracerebral hemorrhage exhibited bleeding in a location that was not associated with hypertension. Callosal and/or juxtacortical location was identified in 58.7% of cerebral microbleed positive images. Features of hemorrhagic necrotizing encephalitis were detected in 28.8% of patients with meningo-/encephalitis. CONCLUSIONS: Manifold CNS involvement is increasingly reported in COVID-19 patients. Typical and atypical neuroimaging features have been observed in some disease entities, so that familiarity with these imaging patterns appears reasonable and may assist clinicians in the differential diagnosis of COVID-19 CNS manifestations.

Porencephaly and psychosis: a case report and review of the literature.

BACKGROUND: Malformations of the cerebral cortex are often associated with developmental delay and psychoses. Porencephaly is a rare congenital disorder of central nervous system involving a cyst or a cavity filled with cerebrospinal fluid, in brain's parenchyma. CASE PRESENTATION: We present a 25 years old woman with her first psychotic episode. She also suffers from porencephaly in the frontotemporal lobes region. It is emphasized that the two consistently abnormal brain regions in schizophrenia research had significant damage in this patient since birth. There is a total of only five cases of schizencephaly or porencephaly associated with psychosis in the scientific literature. Their clinical characteristics as well as the imaging results are described. CONCLUSION: It is unclear if porencephaly and psychosis concur by chance or are causally related. The area where the porencephalic cysts appear seems to be of relevance. This case highlights the need for further research.

Optic nerve sonography in the diagnostic evaluation of adult brain injury.

INTRODUCTION: The optic nerve sheath diameter (ONSD) may be increased in brain-injured patients, especially children, with intracranial hypertension. We investigated whether measurements of ONSD correlated with simultaneous noninvasive and invasive measurements of the intracranial pressure (ICP) in brain-injured adults. METHODS: Seventy-six critical care patients (58 males; 47 +/- 18 years old) were included in the study. Fifty patients suffered from brain injury, whereas 26 had no intracranial pathology and served as control individuals. Initially, brain-injured patients were evaluated clinically (Glasgow Coma Scale) and using a semiquantitative (I to VI) neuroimaging scale (Marshall Scale). Thereafter, the patients were divided into those with moderate (Marshall Scale = I and Glasgow Coma Scale > 8 [n = 18]) and severe (Marshall Scale = II to VI and Glasgow Coma Scale < or =8 [n = 32]) brain injury. All patients underwent noninvasive measurement of the ICP (estimated ICP) by transcranial Doppler sonography, and synchronous ONSD measurements by optic nerve sonography. Finally, invasive ICP measurement using an intraparenchymal catheter was performed in patients with severe brain injury. RESULTS: ONSD and estimated ICP were both significantly increased (6.1 +/- 0.7 mm and 26.2 +/- 8.7 mmHg, respectively; P < 0.0001) in patients with severe brain injury as compared with patients with moderate brain injury (4.2 +/- 1.2 mm and 12.0 +/- 3.6 mmHg) and compared with control individuals (3.6 +/- 0.6 mm and 10.3 +/- 3.1 mmHg). Furthermore, in patients with severe brain injury the ONSD measurements were strongly correlated with estimated ICP values (r = 0.80, P < 0.0001) as well as with the neuroimaging scale results (r = 0.82, P < 0.001). In the patients with severe brain injury, ONSD measurements correlated with invasive ICP values (r = 0.68, P = 0.002). The best cut-off value of ONSD for predicting elevated ICP was 5.7 mm (sensitivity = 74.1% and specificity = 100%). CONCLUSION: ONSD measurements correlate with noninvasive and invasive measurements of the ICP, and with head computed tomography scan findings in brain-injured adults. Hence, optic nerve sonography may serve as an additional diagnostic tool that could alert clinicians to the presence of elevated ICP, whenever invasive ICP evaluation is contraindicated and/or is not available. This trial is International Standard Randomised Controlled Trial Number registered (ISRCTN 91941687).

Lower limb sensorimotor network: issues of somatotopy and overlap.

Functional magnetic resonance imaging (fMRI) was used (1) to describe the pattern of whole brain activity during motion of isolated joints of the lower limb, (2) to examine the somatotopic organization of lower limb joint representations in the primary sensorimotor cortex and the anterior lobe of the cerebellum and 3) to quantify the degree of overlap between these lower limb joint activations. Eighteen healthy, right leg dominant volunteers participated in a motor block-design study, performing repetitive knee, ankle and toes flexion/extension movements. In order to relate lower limb joints activation to the well-described patterns of finger movement, serial finger-to-thumb opposition was also assessed. All movements were auditory paced at 72 beats/min (1.2 Hz). Isolated lower limb joints movement activated a distributed sensorimotor network, including primary and non-primary sensorimotor areas. Although a large overlap was evident in primary sensorimotor cortex (SM1) and cerebellum representations of the three lower limb joints, a somatotopic arrangement was recognizable with reference to center of mass coordinates of each individual joint in the above areas. Detection of active brain regions during movement of the lower limb joints is feasible with fMRI although a carefully optimized methodology protocol is required.

Altered Brain Functional Connectivity in Small-Cell Lung Cancer Patients after Chemotherapy Treatment: A Resting-State fMRI Study.

Previous studies in small-cell lung cancer (SCLC) patients have mainly focused on exploring neurocognitive deficits associated with prophylactic cranial irradiation (PCI). Little is known about functional brain alterations that might occur due to chemotherapy treatment in this population before PCI is administered. For this reason, we used resting-state functional Magnetic Resonance Imaging (fMRI) to examine potential functional connectivity disruptions in brain networks, including the Default Mode Network (DMN), the Sensorimotor Network, and the Task-Positive Network (TPN). Nineteen SCLC patients after platinum-based chemotherapy treatment and thirteen controls were recruited in the current study. ROI-to-ROI and Seed-to-Voxel analyses were carried out and revealed functional connectivity deficits in patients within all the networks investigated demonstrating the possible negative effect of chemotherapy in cognitive functions in SCLC populations.

Prognostic Value of MRS Metabolites in Postoperative Irradiated High Grade Gliomas.

PURPOSE: We studied the prognostic significance of Magnetic Resonance Spectroscopy (MRS) in operated high grade gliomas. MATERIALS AND METHODS: Twelve patients were treated with radiotherapy and Temozolomide. The MRS data were taken four weeks after operation (before radiotherapy) and every six months after the completion of RT. The N-acetyl aspartate, choline, creatine, and myo-inositol parameters were quantified, analyzed, and correlated to recurrence-free survival (RFS). RESULTS: The median RFS was 26.06 months. RFS was significantly worse in elderly patients (P = 0.001) along with the higher choline/creatine ratios at either baseline (P = 0.003) or six months post Radiotherapy (P = 0.042). Median RFS was 23 months in high choline/creatine levels ≥ 2 at 6 months after radiotherapy and 11 months for those with < 2 choline/creatine levels. There was a significant correlation of maximum difference of choline/creatine ratio with RFS (rho = 0.64, P = 0.045). CONCLUSION: Age and choline/creatine ratio are strong independent prognostic factors in high grade gliomas.

Magnetic resonance imaging reveals Creutzfeldt-Jakob disease in a patient with apparent dementia with Lewy bodies.

The differential diagnosis of dementia with Lewy bodies (DLB) and sporadic Creutzfeldt-Jakob disease (CJD) may be challenging. Patients with the original diagnosis of possible CJD may occasionally prove to have a pathological diagnosis of DLB, while other cases may fulfill the diagnostic clinical criteria for DLB but subsequent clinical course, cerebrospinal fluid (CSF) and neuropathology findings necessitate diagnostic revision to CJD. We describe a 79-year old patient recently diagnosed with dementia with Lewy bodies (DLB) on the basis of subacute cognitive decline, visual hallucinations and Parkinsonian features, who presented with increasing agitation. Brain neuroimaging with MRI raised the diagnostic suspicion of CJD and subsequent diagnostic work-up with electroencephalography (EEG) and CSF analysis led to the establishment of CJD diagnosis. The present case highlights the clinical utility of novel diagnostic CJD criteria that also incorporate neuroimaging findings in the diagnostic CJD panel.

A longitudinal study of alterations of hippocampal volumes and serum BDNF levels in association to atypical antipsychotics in a sample of first-episode patients with schizophrenia.

BACKGROUND: Schizophrenia is associated with structural and functional abnormalities of the hippocampus, which have been suggested to play an important role in the formation and emergence of schizophrenia syndrome. Patients with schizophrenia exhibit significant bilateral hippocampal volume reduction and progressive hippocampal volume decrease in first-episode patients with schizophrenia has been shown in many neuroimaging studies. Dysfunction of the neurotrophic system has been implicated in the pathophysiology of schizophrenia. The initiation of antipsychotic medication alters the levels of serum Brain Derived Neurotrophic Factor (BDNF) levels. However it is unclear whether treatment with antipsychotics is associated with alterations of hippocampal volume and BDNF levels. METHODS: In the present longitudinal study we investigated the association between serum BDNF levels and hippocampal volumes in a sample of fourteen first-episode drug-naïve patients with schizophrenia (FEP). MRI scans, BDNF and clinical measurements were performed twice: at baseline before the initiation of antipsychotic treatment and 8 months later, while the patients were receiving monotherapy with second generation antipsychotics (SGAs). RESULTS: We found that left hippocampal volume was decreased (corrected left HV [t = 2.977, df = 13, p = .011] at follow-up; We also found that the higher the BDNF levels change the higher were the differences of corrected left hippocampus after 8 months of treatment with atypical antipsychotics (Pearson r = 0.597, p = 0.024). CONCLUSIONS: The association of BDNF with hippocampal volume alterations in schizophrenia merits further investigation and replication in larger longitudinal studies.