Paraneoplastic Neurological Syndromes as Initial Presentation of Tumors: An Eight-Year Single-Center Experience.

BACKGROUND: Paraneoplastic Neurological Syndromes (PNS) comprise a diverse group of disorders propagated by immune-mediated effects of malignant tumors on neural tissue. METHODS: A single-center longitudinal study was performed including consecutive adult patients treated at a tertiary academic hospital between 2015 and 2023 and diagnosed with PNS. PNS were ascertained using the 2004 and the revised 2021 PNS-Care diagnostic criteria. RESULTS: Thirteen patients who fulfilled the 2004 definite PNS criteria were included. PNS comprise diverse neurological syndromes, with neuromuscular junction disorders (54%) and limbic encephalitis (31%) being predominant. PNS-related antibodies were detected in 85% of cases, including anti-AChR (n = 4), anti-P/Q-VGCC (n = 3), anti-Hu (n = 3), anti-Yo (n = 1), anti-Ma (n = 1), anti-titin (n = 1), anti-IgLON5 (n = 1), and anti-GAD65 (n = 1). Thymoma (31%), small-cell lung cancer (23%), and papillary thyroid carcinoma (18%) were the most frequent tumors. Imaging abnormalities were evident in 33% of cases. Early immunotherapy within 4-weeks from symptom onset was associated with favorable outcomes. At a mean follow-up of 2 ± 1 years, two patients with anti-Hu and anti-Yo antibodies died (18%). Four and three patients fulfilled the 2021 PNS-Care diagnostic criteria for definite and probable PNS, respectively. CONCLUSIONS: This study highlights the clinical heterogeneity of PNS, emphasizing the need for early suspicion and prompt treatment initiation for optimal outcomes.

The Presence of a Zygomatic Nerve Plexus in a Cadaveric Specimen Without a Zygomatic Branch of the Facial Nerve.

The extratemporal course of the facial nerve distributes in facial mimic muscles in a complex pattern. The traditional depictions of five main branches without anastomoses are not common. Davis classification remains the gold standard in the classification of facial nerve branching patterns. During a routine dissection of an 74-year-old male cadaveric specimen, we detected a very rare anatomical variation. The zygomatic branch of the facial nerve was totally absent. The temporofacial division of the main trunk was bifurcated to a temporal and a buccal branch. The anterior temporal and posterior buccal branches formed a plexus to supply the orbicularis oculi muscle. This unique variability highlights the complexity of the extratemporal facial nerve course. Retrograde facial nerve dissection requires deep knowledge of every anatomical variation of the facial nerve course to avoid an iatrogenic injury. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03601-y.

Safety of COVID-19 vaccines in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS). OBJECTIVE: To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types. METHODS: Systematic review and meta-analysis of pharmacovigilance registries and observational studies. RESULTS: Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40-46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9-89.8), 12.6% (95% CI: 6.3-20.8), 6.7% (95% CI: 4.2-9.9), and 2.9% (95% CI: 1-5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12-28.2) from vaccination was 1.9% (95% CI: 1.3%-2.6%; I2 = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine (p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%-8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%-58.8%) and 0.1% (95% CI: 0%-0.2%) of vaccinations, respectively. CONCLUSION: COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.

Clinical, Neuroimaging, and Genetic Markers in Cerebral Amyloid Angiopathy-Related Inflammation: A Systematic Review and Meta-Analysis.

BACKGROUND: There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy-related inflammation (CAA-ri). We sought to determine the prevalence of clinical, radiological, genetic and cerebrospinal fluid biomarker findings in patients with CAA-ri. METHODS: A systematic review and meta-analysis of published studies including patients with CAA-ri was conducted to determine the prevalence of clinical, neuroimaging, genetic and cerebrospinal fluid biomarker findings. Subgroup analyses were performed based on (1) prospective or retrospective study design and (2) CAA-ri diagnosis with or without available biopsy. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using Cochran-Q and I2-statistics. RESULTS: We identified 4 prospective and 17 retrospective cohort studies comprising 378 patients with CAA-ri (mean age, 71.5 years; women, 52%). The pooled prevalence rates were as follows: cognitive decline at presentation 70% ([95% CI, 54%-84%]; I2=82%), focal neurological deficits 55% ([95% CI, 40%-70%]; I2=82%), encephalopathy 54% ([95% CI, 39%-68%]; I2=43%), seizures 37% ([95% CI, 27%-49%]; I2=65%), headache 31% ([95% CI, 22%-42%]; I2=58%), T2/fluid-attenuated inversion recovery-hyperintense white matter lesions 98% ([95% CI, 93%-100%]; I2=44%), lobar cerebral microbleeds 96% ([95% CI, 92%-99%]; I2=25%), gadolinium enhancing lesions 54% ([95% CI, 42%-66%]; I2=62%), cortical superficial siderosis 51% ([95% CI, 34%-68%]; I2=77%) and lobar macrohemorrhage 40% ([95% CI, 11%-73%]; I2=88%). The prevalence rate of the ApoE (Apolipoprotein E) ε4/ε4 genotype was 34% ([95% CI, 17%-53%]; I2=76%). Subgroup analyses demonstrated no differences in these prevalence rates based on study design and diagnostic strategy. CONCLUSIONS: Cognitive decline was the most common clinical feature. Hyperintense T2/fluid-attenuated inversion recovery white matter lesions and lobar cerebral microbleeds were by far the most prevalent neuroimaging findings. Thirty-four percent of patients with CAA-ri have homozygous ApoE ε4/ε4 genotype and scarce data exist regarding the cerebrospinal fluid biomarkers and its significance in these patients.

Neuronal and Neuroaxonal Damage Cerebrospinal Fluid Biomarkers in Autoimmune Encephalitis Associated or Not with the Presence of Tumor.

The aim of this study was to evaluate the association of neuronal damage biomarkers (neurofilament light chain (NFL) and total tau protein (T-tau)) in the CSF of patients with autoimmune encephalitis (AE) with the presence of an underlying malignancy and to determine correlations with patient characteristics. The study comprised 21 patients with encephalitis associated with antibodies against intracellular (n = 11) and surface/synaptic antigens (extracellular, n = 10) and non-inflammatory disease controls (n = 10). Patients with AE associated with intracellular antigens had increased CSF-NFL (p = 0.003) but not T-tau levels compared to controls. When adjusted for age, CSF-NFL but not CSF-T-tau was higher in patients with encephalitis associated with intracellular antigens as compared to those with encephalitis associated with extracellular antigens (p = 0.032). Total tau and NFL levels were not significantly altered in patients with encephalitis associated with extracellular antigens compared to controls. NFL in the total cohort correlated with neurological signs of cerebellar dysfunction, peripheral neuropathy, presence of CV2 positivity, presence of an underlying tumor and a more detrimental clinical outcome. AE patients with abnormal MRI findings displayed higher NFL levels compared to those without, albeit with no statistical significance (p = 0.07). Using receiver operating characteristic curve analysis, CSF-NFL levels with a cut-off value of 969 pg/mL had a sensitivity and specificity of 100% and 76.19%, respectively, regarding the detection of underlying malignancies. Our findings suggest that neuronal integrity is preserved in autoimmune encephalitis associated with extracellular antigens and without the presence of tumor. However, highly increased NFL is observed in AE associated with intracellular antigens and presence of an underlying tumor. CSF-NFL could potentially be used as a diagnostic biomarker of underlying malignancies in the clinical setting of AE.

Diffuse glioma manifesting as normal pressure hydrocephalus: A potential pitfall in diagnosis-a case report.

•Hydrocephalus is rarely reported in patients with diffuse glioma.•We describe a patient with a low-grade glioma presenting a complex phenotype initially masquerading as hydrocephalus of unknown etiology.•The exact pathophysiological mechanism underlying hydrocephalus in the setting of diffuse glioma remains to be elucidated.•Caution is advised regarding hydrocephalus of unknown etiology, reevaluation is necessary.

Hereditary causes of ischemic cerebral small vessel disease.

Hereditary types of ischemic cerebral subcortical small vessel disease (SSVD) are rare, usually autosomal dominant, diseases, due to an abnormality in vessel wall synthesis. They may present with various combinations of migraine with aura, ischemic events (transient ischemic attacks, lacunar strokes) and progressively worsening ischemic lesion load in brain imaging. Eventually, vascular cognitive impairment (usually of the frontal-subcortical type) develops, frequently accompanied by behavioral-psychiatric symptoms and bilateral pyramidal and pseudobulbar signs leading to severe disability and premature death. In some patients, microbleeds and hemorrhagic strokes may be present. Despite their rarity, these disorders offer a statistically homogeneous population (usually without additional pathology such as Alzheimer's disease), suitable for the study of vascular cognitive impairment. The few studies on the relative frequency of these disorders indicate that the most frequent (or rather the least rare), accounting for more than half of patients, is CADASIL, due to mutations of the NOTCH3 gene, followed by COL4A1/A2-related disease, autosomal dominant forms of HTRA1-related disease and leucoencephalopathies with calcifications and cysts. Mutations of TREX1, GLA, FOXC1 and CARASIL are less frequent. Despite the genetic nature of these disorders, their phenotype, severity and rate of progression may be adversely affected by classical cardiovascular risk factors such as hypertension, diabetes, dyslipidemia and smoking and control of these risk factors is strongly advised for all patients.

Anti-NMDA receptor encephalitis presenting as isolated aphasia in an adult.

Anti-NMDA receptor (NMDA-r) encephalitis is a relatively rare cause of autoimmune encephalitis with divergent clinical presentations. We report a case of an adult patient with anti-NMDA-r encephalitis presenting with isolated, abrupt-onset aphasia. Her condition remained unaltered over a period of 6 months. The patients' electroencephalogram findings were typical for NMDA-r encephalitis; however, her magnetic resonance imaging and cerebrospinal fluid analysis were normal. She responded well to immunotherapy, and aphasia eventually resolved. The natural course of the present case contradicts the rapidly progressive nature of typical NMDA-r encephalitis. Furthermore, it broadens the clinical spectrum of anti-NMDA-r encephalitis, to incorporate isolated, nonprogressive aphasia.

Recognition of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) in Two Oligosymptomatic Sisters with Low CADASIL Scale Scores and a Venous Dysplasia: Report of a Novel Greek Family.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) due to mutations of the NOTCH3 gene is the most common cause of inherited cerebral small-vessel disease and one of the genetic causes of migraine with aura. The so-called CADASIL scale has been proposed as a clinical screening tool, and a score of 15 or higher seems useful in identifying patients with high probability of carrying NOTCH3 mutations. We studied a novel Greek family with clinical features compatible with CADASIL. Genetic analysis of NOTCH3 in the 2 living patients revealed the R182C mutation. Both patients had low scores (12 and 14) in the CADASIL scale, probably due to their relatively young age (38 and 37 years, respectively) at which cognitive decline and external capsule involvement have not developed yet. Another unusual feature in the second patient was a venous dysplasia in the parietal lobe. Observations presented here add to the notion that the CADASIL scale, although useful, probably needs a revision, taking into account the patient's age at which the score is calculated.

An Age-Related Morphometric Profile of Skeletal Muscle in Healthy Untrained Women.

There is a paucity of data on muscle biopsies in females of mixed ages in terms of age-related changes. Cross sections of autopsy material including the quadriceps femoris and biceps brachii muscles were obtained from 23 healthy women, aged 24-82 years, who had suffered sudden death. We calculated the percentage of the number, and the mean diameter, of type I and type II muscle fibers within the fascicles as well as in their peripheral parts. The number of type II fibers were shown to reduce significantly with age (p < 0.005), especially in the fascicle periphery, but the percentage of type 1 fibers did not alter significantly. It was noted that type II fibers diminished in size with age, indicating a relationship between fiber size and age. This result became more apparent in the fascicle periphery (p < 0.05). In women, type II muscle fibers were seen to reduce in size and number with advancing age. We postulate that regular physical activity can increase the size of type II muscle fibers, thus helping to both prevent and treat age-related muscle loss.

Oxidative damage to plasma proteins in patients with chronic alcohol dependence: the effect of smoking.

BACKGROUND: Accumulating evidence implicates oxidative stress in ethanol-induced toxicity. Ethanol has been reported to be involved in oxidative damage, mostly in vitro, or in post mortem tissues, while biochemical abnormalities in the blood or serum are scanty or lacking. The aim of the present study was to examine the oxidative status of plasma proteins as markers of oxidative stress in subjects with chronic alcohol dependence (CAD). Since smoking has also been associated with oxidative stress this factor was also considered. PATIENTS AND METHODS: A total of 71 patients with CAD and 61 healthy volunteers of comparable age were included in the study. The protein carbonyl assay was carried out in plasma, as a reliable measure of general oxidative protein damage, in these two groups. RESULTS: Increased plasma protein carbonyls (PCs) were found in patients with CAD as compared with the control group [mean values (nmollmg protein): 4.73+/-1.46 and 3.62+/-0.91 respectively, p<0.000001]. Within the control group, smokers had higher PCs than the non-smokers, however this difference was of marginal significance [mean values (nmol/mg protein): 3.93+/-1.32 and 3.47+/-0.63, respectively]. The CAD group had significantly increased PCs compared with both the smoker and the non-smoker subgroups of the controls (p<0.001 and p<0.0001, respectively). Duration of alcohol consumption, daily alcohol intake, smoke load, folic acid and vitamin B12 levels did not correlate significantly with PC levels. CONCLUSION: The above results support the evidence for systemic oxidative stress in CAD, which must be attributed mainly to alcohol consumption, while smoking may act synergistically.

Interleukin-12 is reduced in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia.

UNLABELLED: Interleukin-12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines, such as Interferon-gamma and Tumor Necrosis Factor-alpha. There is little information about the involvement of IL-12 in the pathophysiology of Alzheimer's disease (AD) and other tauopathies. OBJECTIVES: The objective of our study was to assess the role of IL-12 as a potential marker of immune reactions in patients with AD and frontotemporal dementia (FTD). PATIENTS AND METHODS: We measured by immunoassay cerebrospinal fluid (CSF) IL-12 levels in 19 patients with AD and 7 patients with FTD in comparison with CSF IL-12 levels in 30 patients with non-inflammatory neurological diseases served as neurological control patients (NCTRL). IL-12 levels were correlated with age, age of disease onset, disease duration, MMSE score, and rate of dementia progression. Abeta42 and Total tau (tau(T)) levels in CSF were also measured. RESULTS: Patients with AD had significantly lower CSF IL-12 levels compared with NCTRL patients (p<0.001). Patients with FTD had also lower CSF IL-12 levels compared with NCTRL patients (p<0.05). Age, sex, disease duration and MMSE score did not affect IL-12 levels in any of the groups. In AD a significant positive correlation was noted between IL-12 levels and tau(T) levels (Rs=0.46, p=0.048). CONCLUSIONS: Our findings may suggest a reduced inflammatory reaction during the course of AD and FTD. A neurotrophic role of IL-12 and other proinflammatory cytokines cannot be excluded.

Health status and socioeconomic factors as determinants of physical activity level in the elderly.

BACKGROUND: The aim of our study was to assess the health status and Physical Activity Level (PAL) of the elderly population and determine the role of health status and socioeconomic factors in PAL. MATERIAL/METHODS: A total of 84 subjects (65 men and 19 women) participated in this study. These individuals were living independently, and attending rehabilitation centers for the elderly in Thessaloniki, Greece. The mean age of the subjects was 74.4 years (SD 7.9). Data was collected with a special questionnaire regarding health status and PAL, during individual interviews. RESULTS: The mean PAL value was 1.519, SD 0.115. Significant positive correlation was found between PAL and educational level (r=0.286, p<0.05). Regarding the relation of illnesses to PAL, one-way ANOVA indicated that individuals under treatment for heart arrhythmia and myocardial infarction, as well as those who had undergone a by-pass operation, had higher PAL values (1.659+/-0.0649, 1.551+/-0.093 and 1.613+/-0.0978, respectively) compared to those not suffering from any of these disorders (1.512+/-0.112, 1.515+/-0.118 and 1.508+/-0.112 respectively, p<0.05 for each comparison). Cancer affected PAL negatively. CONCLUSIONS: In conclusion, the elderly spent most of their time carrying out low-intensity activities and did not participate in leisure activities of high or moderate intensity. Educational level was the only socio-economic factor that was correlated to PAL. The positive effect of certain disorders on PAL might be attributed to patients' compliance with physicians' instructions. Further research is necessary.