Perspectives on the diagnosis and management of functional cognitive disorder: An international Delphi study.

BACKGROUND: Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions. METHODS: International experts in cognitive disorders were invited to assess seven illustrative clinical vignettes containing history and bedside characteristics alone. Participants assigned a probable diagnosis and selected the appropriate investigation and treatment. Qualitative, quantitative and inter-rater agreement analyses were undertaken. RESULTS: Eighteen diagnostic terminologies were assigned by 45 cognitive experts from 12 countries with a median of 13 years of experience, across the seven scenarios. Accurate discrimination between FCD and neurodegeneration was observed, independently of background and years of experience: 100% of the neurodegenerative vignettes were correctly classified and 75%-88% of the FCD diagnoses were attributed to non-neurodegenerative causes. There was <50% agreement in the terminology used for FCD, in comparison with 87%-92% agreement for neurodegenerative syndromes. Blood tests and neuropsychological evaluation were the leading diagnostic modalities for FCD. Diagnostic communication, psychotherapy and psychiatry referral were the main suggested management strategies in FCD. CONCLUSIONS: Our study demonstrates the feasibility of distinguishing between FCD and neurodegeneration based on relevant patient characteristics and history details. These characteristics need further validation and operationalisation. Heterogeneous labelling and framing pose clinical and research challenges reflecting a lack of agreement in the field. Careful consideration of FCD diagnosis is advised, particularly in the presence of comorbidities. This study informs future research on diagnostic tools and evidence-based interventions.

Case report: Rapid-onset parkinsonism after a hornet sting.

Neurological manifestations with basal ganglia involvement following Hymenoptera stings are rare and clinically ill-defined conditions. We present a patient with acute parkinsonism non-responsive to levodopa, who developed striatal lesions after a hornet sting. We report his response to immunomodulatory treatment and subsequent clinical and brain magnetic resonance imaging (MRI) follow-up. We also searched the literature for patients with acute extrapyramidal syndromes following an insect sting. Fourteen cases have been published; 12 of them are reviewed here. The majority of cases presented with symmetric akinetic syndrome with axial rigidity and/or gait impairment. Six patients were treated with levodopa and only two of these had a modest response to therapy. Brain MRI/computed tomography scan revealed lesions of the basal ganglia, which resulted in fatal outcome in four patients, whereas only one achieved complete recovery. Clinicians should be aware of this rare but devastating cause of acute-onset parkinsonism and specific clinical presentation of this condition, and should consider prompt and prolonged immunomodulatory treatment to prevent irreversible basal ganglia damage.

Association of intestinal inflammation and permeability markers with clinical manifestations of Parkinson's disease.

INTRODUCTION: Intestinal inflammation and gut microbiota dysbiosis can stimulate degeneration of dopaminergic neurons and development of Parkinson's disease (PD) via the gut-brain axis in certain patients. METHODS: In a case-control study, fecal markers of intestinal inflammation and permeability were measured using the ELISA method in PD patients and healthy controls. Motor and nonmotor symptoms were assessed using the Movement Disorder Society (MDS) Unified PD Rating Scale, Hoehn & Yahr scale, MDS Non-Motor Symptom Scale, Scales for Outcomes in PD - Autonomic Dysfunction, PD Sleep Scale - 2, Montreal Cognitive Assessment, Beck Anxiety Inventory, and Beck Depression Inventory-II. A correlation was established between the intestinal inflammation and permeability markers and PD symptoms. RESULTS: Higher levels of beta-defensin 2, zonulin and lactoferrin were recorded in PD patients compared to controls. Calprotectin and secretory immunoglobulin A showed no significant differences. Regression analysis indicated the roles of beta-defensin 2 and lactoferrin in predicting PD likelihood. Calprotectin yielded positive correlations with disease duration, depression, motor fluctuations, and gastrointestinal symptoms; beta defensin 2 with thermoregulation; and secretory immunoglobulin A with depression. Secretory immunoglobulin A showed negative correlation with age and age at disease onset, while zonulin showed negative correlation with the MDS Unified PD Rating Scale total score. CONCLUSIONS: Fecal markers differed in PD patients compared to controls and correlated with age, disease duration, and some nonmotor symptoms. Future studies should identify the subgroups of PD patients that are likely to develop intestinal inflammation.

Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to CYP27A1 Gene Mutation with Chenodeoxycholic Acid Therapy.

Cerebrotendinous xanthomatosis (CTX) is a genetic disorder of the cholesterol metabolic pathway, most often associated with variants in the CYP27A1 gene. The dysregulation of cholesterol metabolism results in the accumulation of metabolites such as cholestanol, which has a predilection for neuronal tissue and tendons. The condition is treatable with chenodeoxycholic acid (CDCA), which halts the production of these metabolites. We present two adult brothers, without diagnosis, suffering from ataxia, general muscle weakness and cognitive deficits. Both brothers suffered from early onset cataracts, watery stools and thoracic kyphoscoliosis. Magnetic resonance imaging revealed hyperintense alterations in the central nervous system and intratendinous xanthomas in the Achilles tendons. A biochemical analysis showed elevated levels of cholestanol, lathosterol and 7-dehydrocholesterol. Their family history was negative for neurological and metabolic disorders. Genetic testing revealed a pathogenic CYP27A1 variant (c.1184+1G>A) in both brothers, confirming the diagnosis. The patients were started on CDCA therapy and have shown significant improvement at their follow-up examinations. Early diagnosis and treatment initiation in CTX patients is of great importance, as the significant reversal of disease progression can be achieved. For this reason, clinical genetic testing is necessary when it comes to patients with an onset of cataracts, chronic diarrhea, and neurological symptoms in early childhood.

Seborrheic Dermatitis Is Related to Motor Symptoms in Parkinson's Disease.

BACKGROUND AND PURPOSE: Parkinson's disease (PD) patients present with numerous motor and nonmotor symptoms. Seborrheic dermatitis (SD) is reported in 18.6%-59% of PD patients. However, the etiology of SD in PD patients remains unknown. The aim of this study was to determine how motor and nonmotor symptoms, age, sex, and levodopa-equivalent daily dose (LEDD) influence the appearance and severity of SD in PD patients, and then discuss about SD possible etiology based on the obtained results. METHODS: Motor symptoms were evaluated using the Unified Parkinson's Disease Rating Scale part III and nonmotor symptoms were evaluated using the Parkinson's Disease Sleep Scale, Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction, and Non-Motor Symptoms Questionnaire. LEDD was calculated and demographic data on age, sex, disease duration, and symptoms of SD prior to a PD diagnosis were collected. A dermatologist evaluated the skin for SD using the Seborrhea Area and Severity Index. RESULTS: SD was present in 36.1% of the PD patients. There were positive correlations between age, motor-symptoms severity, and SD. After adjusting for age, disease duration, and sex, there remained a positive correlation between the severity of motor symptoms and SD. Patients with moderate-to-severe motor symptoms had more-severe SD symptoms, and their risk of developing SD was 1.8-fold higher. There was no correlation between SD and autonomic dysfunction, sleep disturbances, or other nonmotor symptoms, and no sex difference. CONCLUSIONS: In PD, SD is related to motor symptoms.

Fatigue is related to depression in idiopathic dystonia.

INTRODUCTION: Dystonia is a movement disorder presented with involuntary muscle contraction causing abnormal posture, movement, or both. Besides motor symptoms, patients may also report non-motor symptoms such as pain, anxiety, apathy, depression, sleep problems, fatigue, and cognitive impairment. The etiology of fatigue in patients with dystonia is not yet well understood. AIM: To evaluate the presence of fatigue, depression, anxiety, sleep disorders, and daily sleepiness in patients with focal and segmental dystonia and to determine which of these non-motor symptoms influence the occurrence and severity of fatigue. PATIENTS AND METHODS: Patients were surveyed for symptoms of fatigue, depression, anxiety, night-time sleep problems, and daily sleepiness using the Fatigue Assessment Scale, Beck Depression Inventory II, Beck Anxiety Inventory, Pittsburgh Sleep Questionnaire Index, and Epworth Sleepiness Scale. Demographic data (sex, age, and disease duration) were collected from patient medical records. On statistical analysis, we used SPSS for Windows 10. The level of significance was set at p<0.05. RESULTS: Sixty patients (43 female and 17 male) with focal or segmental dystonia were evaluated. Fatigue was reported by 67.2% of patients. Fatigue (general, physical, and mental fatigue) was found to correlate with depression, anxiety, and sleep problems. Daily sleepiness correlated only with mental fatigue. Disease duration, age, and gender did not influence the symptoms of fatigue. Multiple regression analysis showed that depression mostly predicted symptoms of general, physical, and mental fatigue. CONCLUSION: Depression mostly predicted symptoms of general, physical, and mental fatigue in patients with focal and segmental dystonia.

Dementia and COVID-19, a Bidirectional Liaison: Risk Factors, Biomarkers, and Optimal Health Care.

Cognitive impairment following SARS-CoV-2 infection is being increasingly recognized as an acute and possibly also long-term sequela of the disease. Direct viral entry as well as systemic mechanisms such as cytokine storm are thought to contribute to neuroinflammation in these patients. Biomarkers of COVID-19-induced cognitive impairment are currently lacking, but there is some limited evidence that SARS-CoV-2 could preferentially target the frontal lobes, as suggested by behavioral and dysexecutive symptoms, fronto-temporal hypoperfusion on MRI, EEG slowing in frontal regions, and frontal hypometabolism on 18F-FDG-PET. Possible confounders include cognitive impairment due to hypoxia and mechanical ventilation and post-traumatic stress disorder. Conversely, patients already suffering from dementia, as well as their caregivers, have been greatly impacted by the disruption of their care caused by COVID-19. Patients with dementia have experienced worsening of cognitive, behavioral, and psychological symptoms, and the rate of COVID-19-related deaths is disproportionately high among cognitively impaired people. Multiple factors, such as difficulties in remembering and executing safeguarding procedures, age, comorbidities, residing in care homes, and poorer access to hospital standard of care play a role in the increased morbidity and mortality. Non-pharmacological interventions and new technologies have shown a potential for the management of patients with dementia, and for the support of their caregivers.

Total Antioxidant Status in Stable Chronic Obstructive Pulmonary Disease.

Objective: This study evaluates the total antioxidant status (TAS) in plasma of stable chronic obstructive pulmonary disease (COPD) patients. Earlier studies of their relationship showed inconsistent findings. Patients and Methods: We compared TAS between 90 COPD patients and 30 age- and sex-matched controls (mean age 67 ± 7.9, 87 males and 33 females) according to airway obstruction severity, gender, smoking status (current/ former/ non-smoker), smoking-dose, the number of exacerbations in the previous year, nutritional status and hypercapnia. Results: There were no differences in pack-years between COPD and controls, neither in COPD groups. The median time from the last exacerbation was 5 months (interquartile range 3-8.3). TAS was significant higher in COPD than controls (1.68 [1.55-1.80] versus 1.59 [1.54-1.68], respectively; P = 0.03). TAS was significantly higher in COPD men than women (1.7 [1.6-1.8] versus 1.57 [1.5-1.7], respectively; P = 0.001). In COPD groups, there were no significant differences between the severity of airway obstruction and TAS. We found significant positive correlation between pack-years and TAS in all participants (Rho = 0.429, P = 0.004) and COPD patients (Rho = 0.359, P = 0.02), but not in controls. TAS was a significant predictor of COPD (ß = 3.26; P = 0.04; OR = 26.01; 95% CI: 1.20 to 570.8). We failed to find significant differences between TAS and smoking status, frequency of exacerbations in the previous year, nutritional status and hypercapnia. Conclusion: TAS was a significant predictor of COPD. TAS was a significantly higher in stable COPD than controls, higher in COPD men than women, but there was no significant correlation between TAS and the airway obstruction severity. Our results suggest that it could be appropriate to include the time from the last exacerbation in the oxidant-antioxidant balance analysis of COPD patients.

SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury.

Coronavirus disease (CoVID-19), caused by recently identified severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is characterized by inconsistent clinical presentations. While many infected individuals remain asymptomatic or show mild respiratory symptoms, others develop severe pneumonia or even respiratory distress syndrome. SARS-CoV-2 is reported to be able to infect the lungs, the intestines, blood vessels, the bile ducts, the conjunctiva, macrophages, T lymphocytes, the heart, liver, kidneys, and brain. More than a third of cases displayed neurological involvement, and many severely ill patients developed multiple organ infection and injury. However, less than 1% of patients had a detectable level of SARS-CoV-2 in the blood, raising a question of how the virus spreads throughout the body. We propose that nerve terminals in the orofacial mucosa, eyes, and olfactory neuroepithelium act as entry points for the brain invasion, allowing SARS-CoV-2 to infect the brainstem. By exploiting the subcellular membrane compartments of infected cells, a feature common to all coronaviruses, SARS-CoV-2 is capable to disseminate from the brain to periphery via vesicular axonal transport and passive diffusion through axonal endoplasmic reticula, causing multiple organ injury independently of an underlying respiratory infection. The proposed model clarifies a wide range of clinically observed phenomena in CoVID-19 patients, such as neurological symptoms unassociated with lung pathology, protracted presence of the virus in samples obtained from recovered patients, exaggerated immune response, and multiple organ failure in severe cases with variable course and dynamics of the disease. We believe that this model can provide novel insights into CoVID-19 and its long-term sequelae, and establish a framework for further research.

Impaired cerebrovascular reactivity in chronic obstructive pulmonary disease.

Impaired cerebrovascular reactivity (CVR) is associated with stroke. Cerebrovascular diseases are common comorbidity in chronic obstructive pulmonary disease (COPD) patients. The aim of our study was to quantify CVR in the anterior and posterior cerebral circulation during voluntary breath-holding in COPD patients according to airflow limitation severity. In this cross-sectional study, we compared 90 COPD patients without previous cerebrovascular disease and 30 age- and sex-matched healthy volunteers (mean age 67 ± 7.9, 87 males). Using transcranial Doppler ultrasound and breath-holding index (BHI), we analysed baseline mean flow velocities (MFV) and CVR of middle cerebral artery (MCA) and basilar artery (BA). Our results demonstrated that COPD patients had lower baseline MFV of both MCA and BA than controls. COPD patients had significantly lower BHImMCA and BHImBA than controls (0.8 and 0.7 versus 1.24 and 1.07, respectively; p < 0.001). With the severity of airflow obstruction, there were significant declines of BHImMCA and BHImBA in mild (0.94 and 0.83), moderate (0.8 and 0.7) and severe to very severe COPD (0.7 and 0.6), respectively (p < 0.001). For all participants, we found a significant and positive correlation between forced expiratory volume in one second (FEV1) and BHImMCA (Rho = 0.761, p < 0.001) and between FEV1 and BHImBA (Rho = 0.409, p < 0.001). COPD patients have impaired CVR in anterior and posterior cerebral circulation. Impairment of CVR increase with the airflow limitation severity. CVR is an appropriate marker to identify vulnerable COPD subjects at high risk to develop cerebrovascular disease. Prospective studies are needed for further evaluation.

Forestalling the Epidemics of Parkinson's Disease Through Plant-Based Remedies.

Parkinson's disease (PD) as the second leading neurodegenerative disease, imposes a heavy burden among individuals as well as economies worldwide. The main characteristics of PD is a progressive loss of dopaminergic neurons resulting in the loss of motor function, the occurrence of non-motor symptoms, and cognitive decline. Similar to many other chronic diseases, complementary and alternative therapies (CAT) are very popular for the treatment of this disease. This review evaluates six plants, three each from European and Asian traditional medicinal systems: (1) Atropa belladonna, (2) Hyoscyamus niger, (3) Lepidium meyenii, (4) Aspargus racemosus, (5) Mucuna pruriens L., and (6) Gingko biloba. Atropa belladonna, and Hyoscyamus niger in particular, are better known for their poisonous and narcotic effects than as potentially effective plants for the treatment of neurodegenerative diseases. Ginkgo biloba is one of the most widely cultured plants in Traditional Chinese Medicine with high antioxidant potential which contributes to its neuroprotective/ anti-apoptotic activity. The bioactive compounds, anti-neurodegenerative effects and other neuroprotective effects of all six plants are discussed herein.

Hyperhomocysteinemia influenced malnutrition in Parkinson's disease patients.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disease with many motor and non-motor symptoms. Hyperhomocysteinemia is reported in many PD patients. Homocysteine (Hcy) is reported to be a risk factor for some PD non-motor symptoms. AIM: The aim was to analyze Hcy level and its correlation with physical activity and motor and some non-motor symptoms (depression and cognition) in PD patients. PATIENTS AND METHODS: Patients were surveyed for physical activity and demographic data. Blood samples were obtained for Hcy, vitamin B12, and folic acid determination. The Mini Nutritional Assessment (MNA), Unified Parkinson's Disease Rating Scale (UPDRS) parts III and IV, Hoehn and Yahr (H&Y) Scale, Beck Depression Inventory (BDI), and Mini Mental State Examination (MMSE) were used to assess nutritional status, disease stage, and motor and some non-motor symptoms (depression and cognition) of PD in study patients. RESULTS: We analyzed 34 PD patients. Elevated Hcy level was found in 70.6% of these patients. Patients reporting regular exercise had lower Hcy level (p < 0.025). Hcy level yielded a statistically significant correlation with MNA score (rs = - 0.510; p < 0.003), UPDRS part III (rs = 0.372; p < 0.030), vitamin B12 (rs = - 0.519; p < 0.002), and folic acid (rs = - 0.502; p < 0.003) but not with cognition and depression. There were no statistically significant differences in Hcy level for disease stage either for dyskinesia or "off" periods. CONCLUSION: PD patients are at a risk of hyperhomocysteinemia. Regular physical activity decreases Hcy level, whereas poor motor function increases it. There is correlation between Hcy level and malnutrition in PD patients.

What increases the risk of malnutrition in Parkinson's disease?

Parkinson's disease (PD) patients are at a higher risk of malnutrition. The prevalence has been estimated to 0-24%, while 3%-60% of PD patients are reported to be at risk of malnutrition. To date, there is no clear explanation for malnutrition in these patients. The aim of this study was to determine the prevalence of malnutrition and to analyze factors that influence its appearance. The Mini Nutritional Assessment (MNA) was used to determine normal nutritional status; at risk of malnutrition; and already malnourished status. The Unified Parkinson's Disease Rating Scale (UPDRS) parts III and IV, Hoehn and Yahr scale (H&Y scale), Beck Depression Inventory (BDI), Mini Mental State Examination (MMSE), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale - eating part (QUIP-RS) and Mini Nutritional Assessment (MNA) were used to evaluate the factors affecting patient nutritional status. Out of 96 patients, 55,2% were at risk of malnutrition, while 8,3% had already been malnourished. Age, H&Y scale, UPDRS part III, 'off' periods and depression influence negatively on MNA. More patients with 'off' periods were rigor dominant. Thyroid gland hormone therapy was related to malnutrition, while patients with normal nutritional status used ropinirole more often than pramipexole. Factors affecting nutritional status are age, motor symptoms and stage severity, 'off' states, rigidity dominant type with 'off' states, and thyroid hormone replacement therapy. Ropinirole exhibited the possible 'protective' effect against malnutrition.

Impact of autonomic dysfunctions on the quality of life in Parkinson's disease patients.

Autonomic dysfunctions are part of a spectrum of non-motor symptoms in Parkinson's disease (PD) patients. The aim of the study was to assess the prevalence of autonomic dysfunctions and their influence on the quality of life (QoL) in PD patients, adjusted for age, sex, disease duration and motor symptoms. Patients were evaluated for motor function (Unified Parkinson's Disease Rating Scale, UPDRS part III), disease stage (Hoehn and Yahr scale, H&Y scale), autonomic dysfunction (Scales for Outcomes in Parkinson's disease, Autonomic, SCOPA-AUT) and QoL (Parkinson's Disease Questionnaire-39, PDQ-39). Urinary, gastrointestinal and sexual autonomic dysfunctions were most frequently reported, while the most severe symptoms were reported for sexual and urinary systems. Age and motor symptoms did not correlate with autonomic dysfunction, while disease duration correlated with cardiovascular dysfunction. There were sex differences on the thermoregulation subscale. All types of autonomic dysfunction influenced QoL, mostly gastrointestinal and thermoregulatory dysfunctions, except for sexual one. Many aspects of QoL (activity of daily living, emotion, cognitive functions, communication and social support) except for stigma and mobility were affected by autonomic dysfunctions. Age, disease duration, sex and motor symptoms were not found to affect global QoL scores, but had detrimental effects on different PDQ-39 dimensions. Autonomic dysfunctions influence QoL in more aspects than motor symptoms, age, disease duration and sex. Patients tend to be more stigmatized with motor than non-motor symptoms.

Cervical dystonia and quality of life.

Cervical dystonia is focal dystonia characterized by involuntary movement of the neck muscle, which leads to abnormal head posture. It can be accompanied with pain and tremor. In this study, we evaluated the presence of depression and anxiety in patients with cervical dystonia and the influence of dystonia symptoms on the quality of life. Psychiatric symptoms were evaluated by use of the Beck Depression Inventory (BDI-II) and Beck Anxiety Inventory. Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was used to evaluate the cervical dystonia symptoms. Quality of life was assessed by the craniocervical dystonia questionnaire (CDQ-24) and short form 36 health survey (SF-36). Nineteen patients were analyzed. Most of the patients had mild cervical dystonia (mean TWSTRS 23.89). Depression was present in 42.1 % and anxiety in 57.9 % of the patients. Disability due to cervical dystonia correlated with the occurrence of depression (ρ = 0.534) and anxiety (r = 0.652). Disability was found to significantly influence the stigma, emotional state, pain, daily activity, social life, physical function, and physical and mental disability. Pain influenced some aspects of body pain, physical function, and physical and mental disability. Being associated with disability and pain, cervical dystonia decreases the quality of life in many aspects. Disability also influenced depression and anxiety, which were present in half of study patients. In addition to follow up for cervical dystonia symptoms, patients with cervical dystonia should also be assessed for psychiatric symptoms on routine clinical check-ups. In addition to botulinum toxin, psychopharmaceuticals should be considered as a treatment option in these patients.

Type I persistent proatlantal artery associated with fusiform subclavian artery aneurysm: Report of one case.

We report a 61 years old male presenting with a right cerebral infarction, along with a type I persistent left proatlantal artery (PA), which is a form of primitive carotid-basilar anastomosis. The patient had an absence of the ipsilateral vertebral artery (VA) and hypoplasia of the contralateral VA, while the basilar artery was supplied by the PA. Other vascular anomalies present were a fusiform aneurysm of the right subclavian artery, and an A1 segment aplasia of the hypoplastic anterior right cerebral artery, which originated from the anterior communicating artery. To our knowledge these anomalies were not described previously.