The Role of Nutrition in Neurological Disorders

Cognitive disorders have become important public health issues around the world. Studies evaluating the association between cognitive decline and food timing are lacking. The objective of this study was to examine the potential association between energy intake distribution during the day and cognitive performance in cognitively healthy and mildly cognitive impaired individuals. Data were derived from the ongoing Albion study which includes people aged 40 years or older who have a positive family history of cognitive disorder or concern about their cognitive status. A thorough dietary and cognitive assessment was performed. Participants consuming low energy intake at the beginning of the day or high energy at the end of the day had higher cognitive function compared to participants characterized by the opposite pattern. This trend remained statistically significant even after adjustment for potential confounders (p = 0.043). This study suggests that individuals with worse cognitive function may choose to eat earlier during the day, when cognitive performance is better, and it might be hypothesized that a meal pattern characterized by high energy consumption at the beginning of the day or low energy at the end of the day could be a marker of cognitive impairment. Full article

Children with severe central nervous system (CNS) impairment are at risk of developing various degrees of nutritional deficit that require long-term nutritional intervention. Interventions are most often implemented through enteral nutrition (EN) using commercially manufactured feeds administered via gastro/jejunostomy or nasogastric or nasojejunal tubes. The modality of feeding—continuous feeding or bolus feeding—is dependent on the function of the gastrointestinal tract, particularly the efficiency of gastric emptying. In the literature, the relationship between this type of nutrition and the occurrence of hyperglycaemia is often discussed. In addition, children with chronic neurological diseases are vulnerable to disorders of many mechanisms of neurohormonal counter-regulation related to carbohydrate management, and due to limited verbal and logical contact, it is difficult to recognise the symptoms of hypoglycaemia in such patients. We aimed to assess the carbohydrate metabolism in children with severe CNS impairment, with enteral nutrition delivered via nasogastric, nasoenteral, or percutaneous tubes, based on continuous glycaemic monitoring (CGM) and the measurement of glycated haemoglobin (HbA1c) levels. Materials and methods: This prospective, observational study included nineteen patients (median (25–75 pc) age: 12.75 (6.17–15.55) years) with permanent CNS damage (Gross Motor Function Classification System V) receiving long-term tube enteral feeding, recruited from two paediatric university nutritional treatment centres. Patients with acute conditions and diagnosed diabetes were excluded. The nutritional status and nutritional support were analysed in all the inpatients in accordance with a uniform protocol. Using the CGM system (Medtronic iPro2), glycaemic curves were analysed, and in addition, HbA1C levels were determined in fourteen patients. CGM results were analysed using GlyCulator2.0. Statistical analysis was performed using the Statistica version 11 software (StatSoft Inc. Tulsa, OK, USA). Results: More than half (11/19; 58%) of the patients were undernourished (BMI < 3 pc for age and gender), with the stature age being significantly lower than calendar age (5 (4.5–9) vs. 12.75 (6.17–15.55) years; p = 0.0010). The actual caloric intake was 50 (37.7–68.8) kcal/kg (median; 25–75 pc). In patients fed using the bolus method, the number of calories consumed per day was statistically significantly higher than in children subjected to a continuous feeding supply (56.00 (41.00–75.00) vs. 33.40 (26.70–50.00) kcal/kg BW (body weight; p = 0.0159). Decreases in blood glucose levels below the alarm level (<70 mg/dL) were recorded in fifteen patients (78.9%), including two patients with episodes of clinically significant hypoglycaemia (<54 mg/dL). The minimum and maximum glycaemic values recorded in any individual CGM records were 67 mg/dL (median) (minimum: 41 mg/dL; maximum: 77 mg/dL) and 146 (minimum: 114 mg/dL; maximum: 180 g/dL), respectively, for the entire recording. The maximum percentage of glycaemic concentrations > 140 mg/dL (TAR 140) recorded overnight in children with BMI ≥ 3 amounted to 1.6% vs. 0% in undernourished patients (TAR 140: 0.0 (0.00–1.6%) vs. 0% (0.00–0.0%; p = 0.0375); the percentage of glycaemic concentrations <70 mg/dL in the entire recording was comparable (0.77% (0.13–2.2%) vs. 1.8% (0.5–14.4%) vs. p = 0.2629). There was a positive correlation between the mean daily glucose recorded using the CGM method and patients’ BMI z-scores (R = 0.48, p = 0.0397). No statistically significant relationship was demonstrated between the occurrence of alarm hypoglycaemia events in the CGM records and undernutrition expressed by BMI z-scores (OR = 1.50 (95%CI: 0.16–13.75), the type of diet (for commercially manufactured OR = 0.36 (95%CI: 0.04–3.52), and the modality of diet delivery (for bolus feeding OR = 2.75 (95%CI: 0.28–26.61). Conclusions: In children with chronic OU damage, enteral feeding is associated with a risk of hypoglycaemia, but further studies involving a larger number of patients are needed, and CGM might be a useful tool to estimate the metabolic adequacy of enteral nutritional support in terms of glucose control. Full article

Background: Pathogenic variants in SPG11 cause the most common autosomal recessive complicated hereditary spastic paraplegia. Besides the prototypical combination of spastic paraplegia with a thin corpus callosum, obesity has increasingly been reported in this multisystem neurodegenerative disease. However, a detailed analysis of the metabolic state is lacking. Methods: In order to characterize metabolic alterations, a cross-sectional analysis was performed comparing SPG11 patients (n = 16) and matched healthy controls (n = 16). We quantified anthropometric parameters, body composition as determined by bioimpedance spectroscopy, and serum metabolic biomarkers, and we measured hypothalamic volume by high-field MRI. Results: Compared to healthy controls, SPG11 patients exhibited profound changes in body composition, characterized by increased fat tissue index, decreased lean tissue index, and decreased muscle mass. The presence of lymphedema correlated with increased extracellular fluid. The serum levels of the adipokines leptin, resistin, and progranulin were significantly altered in SPG11 while adiponectin and C1q/TNF-related protein 3 (CTRP-3) were unchanged. MRI volumetry revealed a decreased hypothalamic volume in SPG11 patients. Conclusions: Body composition, adipokine levels, and hypothalamic volume are altered in SPG11. Our data indicate a link between obesity and hypothalamic neurodegeneration in SPG11 and imply that specific metabolic interventions may prevent obesity despite severely impaired mobility in SPG11. Full article

Background: Malnutrition’s prognostic impact in patients with severe stroke requiring ICU admission is not well known. This study aimed to assess the nutritional status of severe stroke patients using the geriatric nutritional risk index (GNRI) and examine the association of GNRI with mortality in that population. Methods: We identified 1145 severe stroke patients requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-III) database and divided them into low GNRI (≤98) or high GNRI (>98) groups. We used a propensity score matching (PSM) method to reduce confounding. Cox proportional hazards regression and restricted cubic splines were used to elucidate the association between GNRI and mortality. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Results: A total of 397 (35%) patients were in the low GNRI group (at risk of malnutrition). After PSM, patients in the low GNRI group still suffered higher mortality compared with the high GNRI group at 28 days (27.9 vs. 20.8%), 90 days (35.5 vs. 25.7%), and 1 year (43.4 vs. 30.9%) (p < 0.05). A low GNRI was significantly associated with an increased mortality (HR: 1.38, 95% CI 1.03–1.86 in 28 days; HR: 1.45, 95% CI 1.11–1.89 in 90 days; HR: 1.51, 95% CI 1.19–1.92 in 1 year). Sensitivity analyses yielded consistent results. Restricted cubic splines showed a progressively decreasing risk of mortality with increasing GNRI scores up to 110, approximately. Conclusion: Severe stroke patients with malnutrition experienced an increased risk of death compared to those without malnutrition. GNRI, as a simple and practical nutritional screening tool, can be used as a routine approach to the nutritional status of stroke patients. Full article

Background: The controlling nutritional status (CONUT) score and the prognostic nutritional index (PNI) score were designed as indicators of patients’ immune-nutritional status. This study aimed to investigate the prognostic impact of the CONUT and PNI scores on long-term recurrent ischemic stroke (RIS) and adverse outcomes for adults with acute ischemic stroke (AIS). Methods: This retrospective study enrolled 991 AIS patients. Multivariable Cox regression models were used to assess the relationships of the malnutritional indices and RIS and major cardiovascular events (MACEs). Results: During a median follow-up at 44 months (IQR 39–49 months), 203 (19.2%) patients had RIS and 261 (26.3%) had MACEs. Compared with normal nutritional status, moderate to severe malnutrition was significantly related to an increased risk of RIS in the CONUT score (adjusted hazard ratio (HR) 3.472, 95% confidence interval (CI) 2.223–5.432, p < 0.001). A higher PNI value tertile (tertile two, adjusted HR 0.295, 95% CI 0.202–0.430; tertile three, adjusted HR 0.445, 95% CI 0.308–0.632, all p < 0.001) was related to a lower risk of RIS. Similar results were found for MACEs. The PNI exhibited nonlinear association with the RIS and both two malnutritional indices improved the model’s discrimination when added to the model with other clinical risk factors. Conclusions: This study demonstrated that the CONUT and PNI are promising, straightforward screening indicators to identify AIS patients with impaired immune-nutritional status at higher risk of long-term RIS and MACEs. Full article

Long-term intake of potential zinc-chelating drugs may cause zinc deficiency. We postulated that zinc deficiency in Parkinson’s disease (PD) patients was related to the intake of drugs such as levodopa. We investigated the relationship between zinc levels and levodopa administration period, dosage, and symptoms of zinc deficiency in PD patients. We measured serum zinc levels and analyzed correlations between serum zinc levels, the levodopa oral administration period, dosage, dosing frequency, and zinc deficiency symptoms including taste disorders. Data analyses were performed using Spearman’s rank correlation coefficient. The mean serum zinc level was 60.5 ± 11.6 μg/dL. The mean administration period for levodopa was 8.0 ± 5.5 years, mean administration frequency 3.4 ± 0.9 times/d, and mean administration dose 420.6 ± 237.1 mg/d. Negative correlations between zinc levels and levodopa dosage and dosing frequency were found. Multiple regression analysis showed a significant correlation with the frequency of levodopa (β = −0.360, p = 0.007). No significant change in clinical symptoms was observed after zinc administration, but anxiety tended to improve. Our results indicated that frequent levodopa administration strongly influenced serum zinc levels which may have alleviating effects on psychiatric symptoms; therefore, preventing zinc deficiency can be important during PD treatment. Full article

Atypical eating habits are more common in children with autism spectrum disorders (ASD) than typically developing (TD) peers. Feeding problems may lead to the double burden of specific nutrient deficiencies and excessive weight gain, with a consequent increase in obesity prevalence. The dietary intake of Italian preschoolers with ASD compared to their TD peers and the impact of their dietary choices on their weight status and relationship to food selectivity (FS) were investigated. Dietary patterns and their associations with body mass index (BMI) were evaluated in 65 children with ASD and 82 peers with TD aged 1.3–6.4 years. Eating habits were assessed with a modified version of a parent-rated semi-quantitative Food Frequency Questionnaire. Moreover, the prevalence of FS and possible links with dietary patterns and BMI were investigated in the ASD group. Children with ASD consumed significantly higher amounts of simple sugars, processed and ultra-processed carbohydrates, both low- and high-fat animal proteins, and lower amounts of vegetables and fruits compared to peers with TD. The obesity rate was 1.5% in children with TD and more than fourfold (6.2%) in children with ASD, although the difference between groups was not statistically significant. FS was significantly more frequent in children with ASD than in peers with TD. Children with ASD and FS showed significantly lower annual intakes of vegetable proteins and fiber (considered essential nutrients for a healthy diet) than children with ASD without FS. Our results showed that children with ASD showed different dietary habits than those with TD, with the higher consumption of energy-dense foods and lower amounts of food-sourced fibers, which could place them at increased risk to develop overweight, obesity, and micronutrient deficiencies later in life. Full article

Introduction: Vitamin B6 is a water-soluble vitamin that is naturally present in many foods and is accessible in many dietary supplements. The three natural forms are pyridoxine, pyridoxal, and pyridoxamine. Both vitamin B6 deficiency and high B6 intake have been described as risk factors for developing peripheral neuropathy (PN). The aim of this systematic review is to characterize and comprehensively describe B6-related PN. Method: A systematic, computer-based search was conducted using the PubMed database. Twenty articles were included in this review. Results: Higher vitamin B6 levels, which usually occur following the taking of nutritional supplements, may lead to the development of a predominantly, if not exclusively, sensory neuropathy of the axonal type. After pyridoxine discontinuation, such patients subjectively report improved symptoms. However, although low vitamin B6 levels can be seen in patients suffering from peripheral neuropathy of various etiologies, there is no firm evidence that low B6 levels have a direct causal relationship with PN. Many studies suggest subjective improvement of neuropathy symptoms in patients suffering from PN of various etiologies after receiving B6 supplementation; however, no data about B6 administration as a monotherapy exist, only as part of a combination treatment, usually with other vitamins. Therefore, the potential therapeutic role of B6 cannot be confirmed to date. Supplementation with vitamin B6, even as part of a nutritional multivitamin supplement, has not been proven harmful at permitted daily doses in patients who already suffer from PN. Conclusion: Current scientific evidence supports a neurotoxic role of B6 at high levels. Although some studies suggest that low B6 is also a potential risk factor, further studies in this area are needed. Full article

The term neuronutrition has been proposed as part of nutritional neuroscience, studying the effects of various dietary components on behavior and cognition. Other researchers underline that neuronutrition includes the use of various nutrients and diets to prevent and treat neurological disorders. The aim of this narrative review was to explore the current understanding of the term neuronutrition as the key concept for brain health, its potential molecular targets, and perspectives of its nutritional approach to the prevention and treatment of Alzheimer’s and Parkinson’s diseases, multiple sclerosis, anxiety, depressive disorders, migraine, and chronic pain. Neuronutrition can be defined as a part of neuroscience that studies the influence of various aspects of nutrition (nutrients, diet, eating behavior, food environment, etc.) on the development of nervous disorders and includes nutrition, clinical dietetics, and neurology. There is evidence that the neuronutritional approach can influence neuroepigenetic modifications, immunological regulation, metabolic control, and behavioral patterns. The main molecular targets in neuronutrition include neuroinflammation, oxidative/nitrosative stress and mitochondrial dysfunction, gut–brain axis disturbance, and neurotransmitter imbalance. To effectively apply neuronutrition for maintaining brain health, a personalized approach is needed, which includes the adaptation of the scientific findings to the genetic, biochemical, psycho-physiological, and environmental features of each individual. Full article

Stroke is currently the second most common cause of death worldwide and a major cause of serious long-term morbidity. Selenium is a trace element with pleotropic effects on human health. Selenium deficiency has been associated with a prothrombotic state and poor immune response, particularly during infection. Our aim was to synthesize current evidence on the tripartite interrelationship between selenium levels, stroke, and infection. Although evidence is contradictory, most studies support the association between lower serum selenium levels and stroke risk and outcomes. Conversely, limited evidence on the role of selenium supplementation in stroke indicates a potentially beneficial effect of selenium. Notably, the relationship between stroke risk and selenium levels is bimodal rather than linear, with higher levels of serum selenium linked to disturbances of glucose metabolism and high blood pressure, morbidities which are, in turn, substrates for stroke. Another such substrate is an infection, albeit forming a bidirectional relationship with both stroke and the consequences of impaired selenium metabolism. Perturbed selenium homeostasis leads to impaired immune fitness and antioxidant capacity, which both favor infection and inflammation; specific pathogens may also contend with the host for transcriptional control of the selenoproteome, adding a feed-forward loop to this described process. Broader consequences of infection such as endothelial dysfunction, hypercoagulation, and emergent cardiac dysfunction both provide stroke substrates and further feed-forward feedback to the consequences of deficient selenium metabolism. In this review, we provide a synthesis and interpretation of these outlined complex interrelationships that link selenium, stroke, and infection and attempt to decipher their potential impact on human health and disease. Selenium and the unique properties of its proteome could provide both biomarkers and treatment options in patients with stroke, infection, or both. Full article

Epilepsy is a long-term neurological condition that results in recurrent seizures. Approximately 30% of patients with epilepsy have drug-resistant epilepsy (DRE). The ketogenic diet (KD) is considered an effective alternative treatment for epileptic patients. The aim of this study was to identify the metabolic role of the KD in epilepsy. Ketone bodies induce chemical messengers and alterations in neuronal metabolic activities to regulate neuroprotective mechanisms towards oxidative damage to decrease seizure rate. Here, we discuss the role of KD on epilepsy and related metabolic disorders, focusing on its mechanism of action, favorable effects, and limitations. We describe the significant role of the KD in managing epilepsy disorders. Full article

Food selectivity (FS) in children with autism spectrum disorders (ASD) is common, and its impact on a nutritional level is known. However, the etiology of gastrointestinal disorders (GID) related to alterations in the intestinal microbiota in children with ASD remains unclear. This article provides a narrative review of the literature on FS from the last 15 years, and its relationship with GID in children with ASD. Sensory aversion in ASD leads to food elimination, based on consistencies, preferences, and other sensory issues. The restriction of food groups that modulate the gut microbiota, such as fruits and vegetables, as well as the fibers of some cereals, triggers an intestinal dysbiosis with increased abundance in Enterobacteriaceae, Salmonella Escherichia/Shigella, and Clostridium XIVa, which, together with an aberrant immune response and a leaky gut, may trigger GID. It is observed that FS can be the product of previous GID. GID could provide information to generate a hypothesis of the bidirectional relationship between FS and GID. Emphasis is placed on the need for more studies with methodological rigor in selecting children with ASD, the need for homogeneous criteria in the evaluation of GID, and the adequate classification of FS in children with ASD. Full article

The nutrition recommendation for most common neurological diseases is to follow national dietary guidelines. This is to mitigate malnutrition, reduce the risk of diet-related diseases, and to help manage some common symptoms, including constipation. Nutrition education programs can support people in adhering to guidelines; hence the aim of this scoping review was to explore what programs have been implemented for adults with neurological diseases. We conducted this review according to a published a priori protocol. From 2555 articles screened, 13 were included (dementia n = 6; multiple sclerosis n = 4; stroke survivors n = 2; Parkinson’s n = 1). There were no programs for epilepsy, Huntington’s, and motor neurone disease. Program duration and number of sessions varied widely; however, weekly delivery was most common. Just over half were delivered by dietitians. Most did not report using a behavior change theory. Commonly used behavior change techniques were instruction on how to perform a behavior, credible source, and behavioral practice/rehearsal. Evidence of nutrition education programs for adults with neurological diseases is lacking. Of those that are published, many do not meet best practice principles for nutrition education regarding delivery, educator characteristics, and evaluation. More programs aligning with best practice principles are needed to assess characteristics that lead to behavior change. Full article

Wernicke encephalopathy (WE) is a well-known neurological condition caused by thiamine (vitamin B1) deficiency that occurs in both alcoholic and non-alcoholic populations. We aimed to report a case of a patient with WE who presented with dysphagia and dysphonia and later developed typical symptoms of thiamine deficiency and to conduct a systematic review of the literature on this rare presentation of WE. We searched two databases (PubMed and Scopus) and included publications up to November 2022. We found 12 cases of WE and dysphagia, aged between 12 and 81 years; swallowing problems presented at the onset in nine patients (including the current case report). Our findings suggest that thiamine deficiency should be suspected in patients with dysphagia of unknown cause, even in the absence of alcohol abuse. In contrast to most WE patients, the majority of patients included in this review presented with dysphagia at the onset of their disease, even in the absence of the classic triad of cognitive impairment, ataxia, and oculomotor abnormalities, indicating that there could be varying susceptibilities to clinical manifestations of thiamine deficiency in different brain regions. Full article