Predictive Values of the CHA2DS2-VASc Score and Left Atrial Diameter for Cerebral Small Vessel Disease in Geriatric Patients With Atrial Fibrillation.

Objective The objective of this study was to determine whether the CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, age, sex) score and left atrial diameter (LAD) could predict the presence of cerebral small vessel disease (cSVD) in patients older than 65 years with atrial fibrillation as the cause of ischemic stroke. Materials and methods In this study, we included patients over 65 years of age who had suffered an ischemic stroke caused by atrial fibrillation within 30 days after the onset of symptoms. The data recorded included demographics, electrocardiograms, Holter monitors, and echocardiography reports. The anteroposterior LAD, determined by transthoracic echocardiography, was analyzed. Each patient's CHA2DS2-VASc score was calculated. Brain magnetic resonance imaging (MRI) assessed white matter hyperintensities (WMH) on fluid-attenuated inversion recovery (FLAIR) images and cerebral microbleeds (CMBs) on susceptibility-weighted sequences. The Fazekas score, based on WMH on MRI, was used to grade the severity of gliosis. Participants were categorized into three groups according to their quantitative CMB burden. Findings The study included 60 participants, with a mean age of 80 years (range 65-99), and 43.3% (n = 26) were male. The CHA2DS2-VASc score had a mean value of 4.21 (range 2-8), and the mean LAD was 4.17 (range 2.6-5.3) cm. The CHA2DS2-VASc score did not predict CMBs (OR, 1.389; 95% CI, 0.961-2.008, p = 0.08) in geriatric stroke patients with atrial fibrillation. However, in the subgroup of patients with diabetes mellitus, the CHA2DS2-VASc score was higher in those with CMB 1-4 and CMB ≥ 5 than in those without CMB. Additionally, the risk of CMBs 1-4 increased with higher LAD compared to patients without LAD. Conclusion The LAD and CHA2DS2-VASc scores were not significantly associated with CMB prediction in elderly stroke patients with atrial fibrillation. In a diabetes mellitus subgroup, the CHA2DS2-VASc score was indicative of CMB. An increased LAD elevates the risk of CMBs in patients with coronary artery disease.

Association of Dilated Perivascular Spaces With Lipid Indices in Ischemic Stroke Patients.

Background Dilated perivascular spaces (dPVS) in the basal ganglia are associated with aging, vascular risk factors, and other magnetic resonance imaging (MRI) markers of cerebral small vessel disease (cSVD). While high blood lipids are a well-demonstrated risk factor for large artery atherosclerosis, their role in cSVD remains largely elusive. Methods We evaluated lipid profiles, cardiovascular risk factors, and brain MRI findings in patients with ischemic stroke or transient ischemic attack. We analyzed the extent of dPVS, cerebral microbleed (CMB), and cerebral white matter hyperintensities (WMHs) as MRI indices of cSVD and investigated associations of dPVS with lipid parameters and other cSVD indices. Results Our study enrolled 173 patients with ischemic stroke or transient ischemic attack. The mean age was 68.38±14.31 (range 35-99) years, and 57.8% (n=100) of patients were male. dPVSwere detected in 97% (n=168) of the patients. Among the whole population, half of the patients (n=87) had moderate to severe dPVS. According to the univariate analysis, age, hypertension, previous antiaggregant and/or anticoagulant use, and the high-density lipoprotein to low-density lipoprotein (HDL/LDL) ratio but not other lipid profiles, cerebral microbleed load, and cerebral white matter hyperintensities severity were found to be positively associated with dPVS number in the basal ganglia. After multivariate logistic regression analysis, only age and WMH severity remained statistically significant. Conclusions dPVS are closely associated with other cSVD subtypes and aging. The studied lipid indices were not independently associated with moderate to severe dPVS in basal ganglia in ischemic stroke patients. The association of each lipid and HDL/LDL ratio needs to be further studied with a larger number of participants.

Intracranial tuberculomas or neurocysticercosis: differentiated by cervical lymph node pathology.

Background: Diagnosis of tuberculomas can be difficult in the absence of pulmonary involvement due to numerable mimics. Case report: We report an immunocompetent 20-year-old female patient, who was admitted with new-onset generalized seizure. Cranial magnetic resonance imaging (MRI) revealed multiple ring-enhancing lesions. There was no reported systemic symptom such as weight loss, fever or night sweating. Polymerase chain reaction for SARS-COV-2 was negative. Computed tomography of thorax was normal. With an initial diagnosis of neurocysticercosis, she was treated with albendazole for one month. Follow-up cranial MRI showed no improvement. On follow-up visit, an enlarged cervical lymph node was recognized. Biopsy of the lymph node led to the diagnosis of tuberculosis. Two months after the onset of anti-tuberculosis therapy, follow-up cranial MRI showed near-complete resolution. Conclusion: Investigation of any involvement of disease other than the central nervous system can enable accurate and timely diagnosis of tuberculomas in the absence of pulmonary involvement.

Axial posture disorders in Parkinson's disease: Clinical correlates and future treatment directions1.

BACKGROUND: Postural disorders are frequently observed in Parkinson's disease (PD). The underlying mechanisms that cause postural disorders are not fully understood and the majority of these disorders have no response to antiparkinsonian treatments. These disabling conditions require further investigation to better understand the underlying mechanisms in order to develop effective treatments. OBJECTIVE: The aim of this study was to investigate the frequency of axial postural disorders in PD and to determine the associated clinical risk factors. METHODS: In this single-center clinical trial, the data of PD patients were reviewed retrospectively. The frequencies of postural disorders were determined, and the demographic clinical characteristics of the patients were compared. RESULTS: The records of 127 patients with idiopathic PD were analyzed. Axial posture disorders were found in 42.6% of patients. Patients with axial posture disorders were older when the disease onset was detected, amongst these patients the condition was also longer lasting. The mean levodopa dose was higher in the patients with posture disorders. The initial symptom was bradykinesia and the Hoehn and Yahr's score was ⩾ 3 in the majority of the patients with posture disorder. Additionally, constipation, hallucinations, postural instability, and falls were significantly more common in patients with posture disorders. CONCLUSION: Posture disorders were observed in nearly half of PD patients and were more frequently observed in patients with an advanced condition. In addition, our investigation has found that it is crucial to follow up with patients who present with bradykinesia for the development of postural disorder.

Fingolimod in Multiple Sclerosis and Familial Mediterranean Fever Coexistence.

Background: There is an intriguing relationship between familial Mediterranean fever (FMF) and multiple sclerosis (MS). While FMF is a hereditary autosomal recessive disease characterized by recurrent, acute, self-limited attacks of fever and polyserositis, MS is a chronic, inflammatory demyelinating disease of the central nervous system, characterized by autoreactive lymphocytes, microglial activation, and chronic neurodegeneration. In patients suffering from both FMF and MS, it would be interesting to test whether treatments for MS affect the course of FMF, or vice versa. However, this interaction has not been studied yet. Case Presentation: Herein is reported a case with FMF and relapsing-remitting MS in whom fingolimod, an immunomodulatory oral MS therapy, led to near-complete resolution of FMF symptoms. Conclusion: This report demonstrates an interesting clinical observation which may have promise for patients suffering both from MS and FMF. The drug's effect on the course of FMF needs further research.

A combined clinical and computational approach to understand the SOD1A4T-mediated pathogenesis of rapidly progressive familial amyotrophic lateral sclerosis.

Here, we aim to provide a comprehensive clinical and biomolecular description of familial amyotrophic lateral sclerosis (fALS) in a 25-year-old female patient with respect to the SOD1A4T genotype. The clinical diagnosis of the disease was based on family history, neurological examination, electroneurophysiological studies, and revised El Escorial criteria. The heterozygous presence of the A4T mutation in the proband was confirmed by PCR coupled with Sanger sequencing of exon 1 of the SOD1 gene. The mutation was introduced in silico into the three-dimensional structure of the native protein. After energy minimization and quality assessment, non-covalent interactions around threonine-4 and changes in protein stability were calculated computationally. The patient differed widely in age at onset, initial neurological symptoms and findings, and survival time from her kindred, in which several members are affected. SOD1A4T-linked fALS in this case had bulbar involvement at onset, a combination of lower and upper motor neuron signs and showed rapid progression. Unlike alanine-4, threonine-4 failed to engage in hydrophobic interactions with the vicinal non-polar amino acids. The overall fold of the modeled SOD1A4T mutant remained intact, but unfolding free energy estimations disclosed a decrease in the protein's stability. We report a phenotypically distinct patient with fALS due to the SOD1A4T mutation and further expand the largest pedigree ever published for SOD1A4T-linked fALS. Genotype‒phenotype correlation in fALS is complex, and it demands detailed clinical investigation and advanced scientific research. Awareness of the broadened phenotypic spectrum might potentially enhance the diagnosis and genetic counseling of fALS.

Trigeminal neuralgia in a patient with multiple sclerosis: Coincidental? An attack? Teriflunomide-induced?

Trigeminal neuralgia attributed to multiple sclerosis (TNMS) occurs in 2% to 5% of patients with multiple sclerosis (MS). Although treatment strategies are similar to those for classic trigeminal neuralgia, TNMS tends to become medically resistant and require polytherapy. Demyelinating lesions in critical regions are the most common etiology. However, therapies used to treat MS may trigger trigeminal neuralgia, as well as other pain disorders, like migraines or daily headaches. Presently reported is the case of a patient with MS who suffered severe trigeminal neuralgia 5 months after switching to teriflunomide, an oral immunomodulator drug approved for relapsing-remitting MS, and a discussion of possible etiological factors for the development of trigeminal neuralgia.

Adult-onset glutaric aciduria type I: rare presentation of a treatable disorder.

Glutaric aciduria type I (GA1; OMIM #231670) is an autosomal recessively inherited and treatable disorder characterized by the accumulation and irregular excretion of glutaric acid due to a defect in the glutaryl-CoA dehydrogenase enzyme involved in the catabolic pathways of L-lysine, L-hydroxylysine, and L-tryptophan. Glutaryl-CoA dehydrogenase is encoded by the GCDH gene (OMIM #608801), and several mutations in this gene are known to result in GA1. GA1 usually presents in the first 18-36 months of life with mild or severe acute encephalopathy, movement disorders, and striatal degeneration. Few cases of adult-onset GA1 have been described so far in the literature, often with non-specific and sometimes longstanding neurological symptoms. Since a preventive metabolic treatment is available, neurologists must be aware of this rare but likely underdiagnosed presentation, especially when typical neuroimaging features are identified. Here, we describe 35-year-old presenting with headache and subjective memory problems. There was no history of dystonic movement disorders. Neurological examination and neurocognitive tests were normal. Brain MRI scan revealed white matter abnormalities associated with subependymal nodules and mild frontotemporal hypoplasia suggestive of glutaric aciduria type 1 (GA1). Genetic testing confirmed the presence of homozygous c.1204C > T (p.R402W) variant in the GCDH gene, inherited from heterozygous parents.

Optic atrophy after cabazitaxel treatment in a patient with castration-resistant prostate cancer: a case report.

Taxanes are a group of cytotoxic anti-cancer agents used in the treatment of solid tumours. The neurotoxic adverse effects of docetaxel and paclitaxel, including optic neuropathy, are well known. Cabazitaxel is a new generation taxane showing lesser drug resistance when compared with previous ones. Optic atrophy due to the use of cabazitaxel has not been previously reported. Herein, we report a patient with prostate cancer who developed optic atrophy after cabazitaxel treatment.

Neuroinvasive Listeriosis: Could Petechial Hemorrhages be a Diagnostic Clue?

INTRODUCTION: Listeria monocytogenes-related central nervous system infections may involve the cerebral parenchyma. Meningitis and meningoencephalitis are the most commonly seen forms and mainly affect immunocompromised patients; however, a less frequent form, rhombencephalitis, can occur in otherwise healthy people. Early treatment with appropriate antibiotic therapy is crucial for this otherwise fatal disorder. However, it is not always possible to rapidly establish the diagnosis because of varying presentations and discrepancies in diagnostic tests. CASE REPORT: Herein we report 3 cases of listerial infections involving the central nervous system parenchyma, with versatile diagnostic challenges and related possible solutions and radiologic hints to overcome similar issues in the future. CONCLUSIONS: We point out the importance of nonconventional magnetic resonance imaging techniques in the diagnosis, as we detected petechial hemorrhages in the brain parenchyma in all cases, which can be a diagnostic clue.

The association of cognitive impairment with gray matter atrophy and cortical lesion load in clinically isolated syndrome.

BACKGROUND: Multiple sclerosis can impair cognition from the early stages and has been shown to be associated with gray matter damage in addition to white matter pathology. OBJECTIVES: To investigate the profile of cognitive impairment in clinically isolated syndrome (CIS), and the contribution of cortical inflammation, cortical and deep gray matter atrophy, and white matter lesions to cognitive decline. METHODS: Thirty patients with clinically isolated syndrome and twenty demographically- matched healthy controls underwent neuropsychologic assessment through the Rao Brief Repeatable Battery, and brain magnetic resonance imaging with double inversion recovery using a 3T scanner. RESULTS: Patients with clinically isolated syndrome performed significantly worse than healthy controls on tests that evaluated verbal memory, visuospatial learning and memory, and verbal fluency. Significant deep gray matter atrophy was found in the patients but cortical volume was not lower than the controls. Visual memory tests correlated with the volume of the hippocampus, cerebral white matter and deep gray matter structures and with cerebellar cortical atrophy. Cortical or white matter lesion load did not affect cognitive test results. CONCLUSION: In our patients with CIS, it was shown that cognitive impairment was mainly related to cerebral white matter, cerebellar cortical and deep gray matter atrophy, but not with cortical inflammation, at least in the early stage of disease.

Influence of cigarette smoking on white matter in patients with clinically isolated syndrome as detected by diffusion tensor imaging.

PURPOSE: Cigarette smoking has been associated with increased occurrence of multiple sclerosis (MS), as well as clinical disability and disease progression in MS. We aimed to assess the effects of smoking on the white matter (WM) in patients with clinically isolated syndrome (CIS) using diffusion tensor imaging. METHODS: Smoker patients with CIS (n=16), smoker healthy controls (n=13), nonsmoker patients with CIS (n=17) and nonsmoker healthy controls (n=14) were included. Thirteen regions-of-interest including nonenhancing T1 hypointense lesion and perilesional WM, and 11 normal-appearing white matter (NAWM) regions were drawn on color-coded fractional anisotropy (FA) maps. Lesion load was determined in terms of number and volume of WM hyperintensities. RESULTS: A tendency towards greater lesion load was found in smoker patients. T1 hypointense lesions and perilesional WM had reduced FA and increased mean diffusivity to a similar degree in smoker and nonsmoker CIS patients. Compared with healthy smokers, smoker CIS patients had more extensive NAWM changes shown by increased mean diffusivity. There was no relationship between diffusion metrics and clinical disability scores, duration of the disease and degree of smoking exposure. CONCLUSION: Smoker patients showed a tendency towards having greater number of WM lesions and displayed significantly more extensive NAWM abnormalities.

Assessment of the effect of cigarette smoking on regional brain volumes and lesion load in patients with clinically isolated syndrome.

PURPOSE: Smoking has been associated with an increased risk of developing multiple sclerosis, disease progression and clinical disability. We detected the effects of smoking on regional brain volumes and lesion load in patients with clinically isolated syndrome using quantitative magnetic resonance imaging. MATERIALS AND METHODS: Smoker patients (n = 16), smoker healthy controls (n = 13), non-smoker patients (n = 17) and non-smoker healthy controls (n = 14) underwent magnetic resonance imaging and neocortical volumes were measured. Lesion load was calculated in terms of number and volume of white matter hyperintensities. RESULTS: Smoking was associated with increased gray matter volumes in several regions of the brain. A tendency towards greater lesion load in smoker patients was found. Smoking duration was significantly negatively correlated with intracranial volume and left hemisphere cortical gray matter volume. There was no relationship between regional brain volumes and clinical disability scores, lesion load duration of the disease and degree of smoking exposure. CONCLUSIONS: Clinically isolated syndrome related regional brain atrophy might vary in extent and severity with smoking. Despite increased lesion load, less cortical and deep gray matter damage with a possible neuroprotective effect occurs in smoking.

Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorder Patients in Turkish Cohort: Demographic, Clinical, and Laboratory Features.

BACKGROUND: Neuromyelitis optica (NMO) is an immune-mediated, chronic relapsing, inflammatory disease characterized by severe attacks of optic neuritis and myelitis. OBJECTIVE: To determine the demographic, clinical, and laboratory features; antibody status; and treatment modalities of patients with NMO and neuromyelitis optica spectrum disorders in a Turkish cohort from 11 centers. METHODS: A total of 182 patients were included in this study. Data on age at disease onset, sex, type of attacks, clinical presentation, analysis of cerebrospinal fluid, serum antiaquaporin-4 antibody status, annual progression index, and medical and family histories were collected. RESULTS: Mean age was 38.43±12.40 years (range, 13 to 75 y), and mean age at disease onset was 31.29±12.40 years (median, 29 y; range, 10 to 74 y). In NMO group, the rate of NMO immunoglobulin (Ig)G positivity was 62.5%. The annual progression index was significantly higher in the longitudinally extending spinal cord lesion. The mean Expanded Disability Status Scale score was higher in the late than early-onset NMO group. CONCLUSION: Our results revealed a lower rate of NMO IgG positivity, more severe disability in patients with NMO/neuromyelitis optica spectrum disorders presenting with either transverse myelitis or late-onset NMO, and no correlation between disability and NMO IgG status.