Nutritional Care and Intervention in Spinocerebellar Ataxia

Abstract

This chapter examines the link between nutritional health outcomes in clients diagnosed with spinocerebellar ataxia as well as generalized quality of life and well-being that is achieved as a result of nutritional intervention and concordant nutritional status. Spinocerebellar ataxia is a familial disorder typified by degenerative changes to the neurological system including the brain, and spinal cord, impacting mobility and volitional actions. Due declining neural activity, the management of health and wellness in the affected individuals is central to mitigating the functional decline and morbidity. The linkage between dietary intake and nutritional support is a significant element of the health care interventions necessary to provide optimal health outcomes in clients diagnosed with spinocerebellar ataxia. Accordingly, an analysis of factors that impact dietary intake, and nutritional profile is pivotal in regulating disease progression, remission and management. The isochronous relationship between nutritional support and spinocerebellar ataxic progression and the concordant impact of disease progression on nutritional outcome is a critical subject for review. Lastly, summative standardized models are essential to guiding the health care strategy for managing the wellbeing of individuals with spinocerebellar ataxia.

1. Introduction

The global prevalence of spinocerebellar ataxia is 1 to 5 per 100,000 but higher in Asian populations while lower in European countries [1]. Ataxia is the loss of neural control over muscular tone and function affecting gait, coordination, eye movement, and speech; swallowing and other voluntary activities are also affected. Spinocerebellar ataxia (SCA) is a large and complex group of hereditary (genetic, familial), progressive, neurodegenerative, and heterogeneous disease that mainly affects the cerebellum. SCA is a subgroup of inherited cerebellar ataxia and is a rare disease. Currently, in excess of 40 distinctive genetic SCAs have been identified. The genetic contributions and impact of SCA is very complex to understand but is critical to diagnosing and classifying the disease which determine treatment approaches [1, 2]. SCA presents clinically with several symptoms related to the neuromuscular systems and is characterized by cerebellar gait and limb ataxia (with dysmetria, dysdiadochokinesia, intention tremor, dysarthria, and nystagmus), which may be present together with extracerebellar signs, such as ophthalmoplegia, pyramidal signs, movement disorders (including parkinsonism, dystonia, myoclonus, and chorea), dementia, epilepsy, visual disorders (including pigmentary retinopathy), and peripheral neuropathy. These symptoms contribute to significant physiological impact which influences Disability Adjusted Life Years (DALY). One DALY is the equivalent of one healthy life-year lost and contributes to the global disease burden [3, 4]. Individuals diagnosed with SCA may present clinically with self care deficits and experience increased nutrient requirements coupled with limitations in dietary intake. The progressive nature of the disease makes it critical for early nutritional intervention and management to correct, resolve and limit the negative health and nutrition outcomes associated with the disease. Consequently, health care practitioners must collaborate to create the best therapeutic outcome for the client diagnosed with SCA.

2. Overview of nutrition and neurological health

Nutrition is a key determinant of overall physical wellness and as a consequence specific neurological function and wellness. Nutrition has been identified as a strong modifier of healthy aging, body composition and physical function [5, 6, 7]. Through dietary intake, people acquire the related nutrients, substrates, and components necessary to maintain health and carry out life sustaining functions and reactions. To illustrate, a meal consisting of chicken provides protein to an individual who consumes it. Following digestion, deamination, transamination, and the Krebs cycle, proteins are catabolized either to energy in the form of adenosine triphosphate (ATP) or may enter the amino acid pool which produces substrates for physiological processes such as coagulation, immunity, muscle accretion or enzymatic support [8]. When nutritional adequacy is achieved through balanced dietary intake physiological homeostasis is attained and wellness equilibrium is established. Where dietary intake is discordant with requirements and nutritional needs remain unsatisfied, individuals may experience metabolic stress, catabolic changes and physiological impairments. This physiological wellness is a primary underpinning concept of overall wellness and is important for establishing optimum neurological status.

Furthermore, normal neurological status and functioning is a state that occurs when genetic, biological and physiological conditions are optimal. While genetic and biological conditions are largely non modifiable conditions; nutrition is an important regulatory on the physiological contributions to optimal neurological status. Importantly optimal neurological status requires a constant supply of some chemical substrates, known as neurotransmitters, which are essential to the typical signaling in the brain. Glutamate, glycine, γ-Aminobutyric acid (GABA) and acetylcholine are the key neurotransmitters in degenerative neurological disorders that are influenced by dietary intake. Spinocereballar ataxia (SCA) has been described as a heterogenous autosomal degenerative disease with multiple subtypes affecting both sensory and motor function with significant progressive decline which affects self care and independent functioning. The evidence suggests a clear genetic anomaly impacting the development of the condition. Some studies use metabolomics to identify associated biomarkers that are linked to the development of the disease. Metabolomics is a recent powerful scientific strategy used to identify and measure potential biomarkers, especially metabolites and small molecular weight molecules, in neurodegenerative diseases capable of determining alterations in brain function which can be affected by metabolite composition of biological fluids such as the serum, plasma, and cerebrospinal fluid. Amino acids including but not limited to Valine, Leucine, and Tyrosine have been linked to the development, diagnosis and sequencing of spinocerebellar ataxia [9]. Other evidence supports this finding but expands the report to include challenges with glutamine and calcium regulation as contributing metabolites to SCA development [10].

In some sub types of spinocerebellar ataxia, the evidence suggests that the ability to recover normal function reduces as the client ages and the disease develops. Therefore, recent studies recommend early therapeutic intervention for a better chance of having a positive neurological impact [11]. Molecular studies support these recommendations insomuch as they demonstrate that dietary amino acid intake produces substantial effects on health and disease by modulating metabolism. Recent studies have shown that newer dietary patterns, such as the ketogenic diet and the Paleo diet, have recorded clinical benefits on metabolic health, neural function, and longevity [12]. While the literature is expansive concerning the recommendations for carbohydrates and fats in health and wellness, protein requirements are usually given as a single nutrient recommendation rather than disaggregated by monomeric stratification. The current data proposes that amino acids, the building block of proteins, are unique in their functions and biological requirements are variable. Amino acids such as serine, glycine, asparagine, histidine, and methionine mediate health and disease including cancer and neurological disorders through defined molecular mechanisms [12, 13]. Some of these amino acids, histidine and methionine, are essential which means the human body lacks the biological capacity to make them and they must therefore be supplied by the diet. Others, though non essential and able to be made de novo, require sufficient substrates for development. This creates a unique conundrum for clients diagnosed with SCA because as the physiological need for amino acids rises, physical factors such as coordination and dependency limit their intake which may result in true or functional deficiency.

Consistent with these findings are the therapeutic recommendations which suggest that increased availability of these amino acids is beneficial to neurological health. Targeted pharmacological and therapeutic approaches have been consistently used to increase the availability of these amino acids in translation and gene expression, especially in neurological disorders, such as through induced pluripotent stem cell but not much has been done to explore and create consensus concerning the nutritional contributions of these amino acids in neuropharmacotherapy. The evidence suggests that foods such as eggs, cheeses, pineapples, nuts and seeds and salmon have been shown to significantly improve mental health outcomes [14]. These foods are high in tryptophan (an essential amino acid) that is critical to neurological activity. Similarly, dairy products including milk, cheese and dark chocolate, as well as eggs, beef, chicken, salmon, trout and legumes have been identified to be rich in histidine, methionine, leucine and other essential amino acids as well as the non essential serine that are linked to neurological health [15, 16]. Serine has been isolated as an important amino acid that modifies the health outcomes in neurological conditions affecting both sensory and motor activities [17].

Notably, dietary intake and interventions directly affects physiological health and mental wellness through its general supply of substrates of homeostasis. Specifically, diet supplies neurotransmitters necessary for the signaling of nerves. A concerted effort, of the multidisciplinary health care team, needs to be employed to ensure dietary adequacy for normal neurological functioning and to assist in recovery where sensory and motor neurological disorders exist.

2.1 Nutrient metabolism and brain health

Although the brain only accounts for two percent of the body’s weight, it utilizes a quarter of the ingested energy of the human’s body. It primarily utilizes glucose as the source of energy and so prefers carbohydrate as the main macronutrient source. It relies on aerobic respiration and oxidative processes for energy production and cellular activity [18]. An important part of neurons is the phospholipid coating that supports quick transmission of nerve impulses. Unlike organs such as muscles, liver and kidney, the brain has very limited energy stores and relies on a constant dietary supply of macro and micronutrients to meet dietary needs. The brain utilizes one fifth of the total blood glucose for daily functioning and only stores small amounts of glycogen in astrocytes. Carbohydrate promotes good mental health through its positive impact on dopamine levels, serotonin levels and its impact on cortisol release [18, 19]. Complex carbohydrates with lower glycaemic index and sustained energy provision in the blood are better suited to controlled energy supply to the brain.

Similarly fatty acids, phospholipids and polyunsaturated fatty acids such as linoleic acid and linolenic acid have been found to improve synaptic functions and cell signaling [18, 20]. Moreover, amino acids, the protein monomers, have been found to have both naturally positive and negative neuronal impact. Recommended intake of amino acids at physiological concentrations produce nitric acid, taurine and glutathione which promote good mental health but in excess amino acids produce metabolites that are neurotoxic including ammonia and homocysteine [18, 21].

Several studies have linked the B vitamin group to positive mental health outcomes and status. Thiamine, Riboflavin, Niacin, Pantothenic acid, Folate and Cyanocobalamin have all been positively linked to good mental health [18, 22]. These water-soluble vitamins influence and promote energy release as well as macronutrient metabolism, RNA and DNA formation and cellular signaling. Moreover, deficiencies in some of these vitamins have been linked to higher risks of mental illnesses including B9 (Folate) and B12 (Cyanocobalamin). Though energy balance is essential to neuronal homeostasis, current evidence suggests that dysfunctional energy metabolism as well as metabolic impairment may increase the risk of mental illness. The changes in the brain function, cell signaling, nerve conduction and brain activity alters energy utilization and requirements in mental illness [19]. Some evidence also points to risks of metabolic syndrome, impaired glucose tolerance and diabetes as conditions that can arise from muscle relaxant therapy as a part of the pharmacotherapy in spinocerebellar ataxia [23].

2.2 Nutritional requirements and brain health

Current evidence points to higher levels of prooxidant activity, reactive oxygen species and a concordant increased use of antioxidant in some subtypes of SCA. Consistent with this finding is the increased risk of being susceptible to oxidative stress and oxidative cellular damage [24, 25]. Clients with SCA7 exhibit oxidative damage to lipids (high levels of lipid hydroperoxides and malondialdehyde) and proteins (elevated levels of advanced oxidation protein products and protein carbonyls). Furthermore, SCA7 clients showed enhanced activity of various anti-oxidant enzymes (glutathione reductase, glutathione peroxidase, and paraoxonase) as well as increased total anti-oxidant capacity, which suggest that activation of the antioxidant defense system might occur to counteract oxidant damage. Furthermore, clients with degenerative neurological conditions have relatively higher requirements for antioxidants. These molecules are thought to be protective, especially in the neuronal spaces. It has been primarily linked to improved outcomes. Nutrients that are classified as antioxidants include zinc, selenium, ascorbic acid, retinol, and tocopherols. Fruits, vegetables, and fish provide concentrated sources of these nutrients. Additionally, polyunsaturated fatty acids have been strongly linked and examined in mitigating and treating mental illness. At recommended levels essential unsaturated fatty acids including linoleic and linolenic fatty acids support cell signaling, synaptic function and nerve impulse propagation. In degenerative disorders the evidence suggests that the demand for antioxidants is higher, the pathways are upregulated as well as the production of prooxidant species with relatively worsened clinical outcomes [24, 25, 26]. Consequently, consumption of fatty acids at the level of the recommended dietary allowances and fatty acid supplementation have been found to be beneficial in reducing the risks associated with mood disorders and have also been linked to improved recovery from these illnesses.

Some trace elements including zinc, copper and iron and manganese, have been associated with Neurological disorders. Some evidence also describes the link between zinc and neurological and the inverse relationship between zinc supplementation and the resolution of these symptoms [27, 28, 29]. Zinc has been associated with brain function and development and is also a potent antioxidant which combats the actions of prooxidants, superoxides and reactive oxygen species which negatively impact degenerative neurological disorders.

Individuals who experience SCA, have increased needs for nutrients including major minerals, trace elements, and antioxidants as their body utilizes these substrates at a faster rate in view of the increased brain activity. Consumption of high biological value sources, at the Recommended Dietary Allowances and supplementation have been strongly associated with lower illness incidence and better recovery.

2.3 Drug nutrient interaction and spinocerebellar ataxia

The health outcomes of SCA worsens as the disease develops with progressively worse motor and sensory activities with time. In addition to gene therapy as means of reducing and reversing the physical outcomes, clients diagnosed with degenerative neurological disorders are often treated with Riluzole, Antiglutaminergic Medication such as Amantadine, Nicotine Receptor Agonists such as Varenicline and Serotonergic Therapy among other pharmacological options [30, 31]. Collectively these medications may cause reduced appetite, vomiting, diarrhea, weight loss and anorexia and sore throat. While these symptomatic medication targets the improvement in the quality of life of clients affected by SCA, caution must be exercised with their use so that nutrition decline is not potentiated. Appetite loss and Anorexia may reduce the likelihood of clients meeting the recommended dietary allowances (RDA) and the acceptable macronutrient distribution ranges (AMDR) of key macronutrients carbohydrates, proteins and fats and important micronutrients such as zinc, copper, iron and manganese that have been linked to the physiological outcomes of the disease. Diarrhea and vomiting which are other significant side effects of these therapies may contribute to subclinical and clinical deficiencies as plasma levels decline with loss. Therefore, a collaborative holistic multi-team approach is necessary to treat SCA including the dietitian, pharmacist and the medical doctor.

2.4 Altered physical activity and energy metabolism in clients with degenerative disorders

There is a direct proportional relationship between energy requirements and physical activity. More energy is required in individuals who engage in physical activity whether voluntary or involuntary. Clients with neurological conditions, by virtue of the impact on the musculoskeletal system, may either be more or less active and directly have varying energy needs. Clients diagnosed with SCA may experience neurological impact resulting in hyperactivity characterized by involuntary movements. Individuals who are diagnosed with these conditions may experience tremors, muscle spasms and other movement disorders as symptoms of the condition. Moreover, the psychopharmacotherapy used in the treatment of spinocerebellar ataxia has negative side effects including tardive dyskinesia, restlessness and aggression. Alternatively, some clients exhibit reduction in motor activity and dysarthria, limited voluntary activity while on the same medications [11, 32]. These symptoms are at dipoles and require different nutritional therapeutic interventions to meet the physiological needs of the affected clients. In clients with reduced physical activity such as those who experience slow, sluggish movement, energy intake needs to be reduced to prevent obesity and positive energy balance while in clients who experience increased physical engagement as a consequence of increased involuntary activity, increased energy intake through the global increase of all macronutrients is the ideal nutritional therapy suited to these clients. Macronutrients are energy producing nutrients and include protein, carbohydrates and fats that are provided in the diet mainly from eating starches, animal and plant based foods and fruits. Due to the supportive role that micronutrients, especially water soluble B vitamins, play in macronutrient metabolism their requirements are also increased in accordance with energy requirements. These micronutrients serve as cofactors and coenzymes in energy metabolism so that energy can be increase from consuming the calorie containing foods [33]. Alternatively, another physiological feature of SCA, that results in reduced dietary intake is reduced swallowing capacity and coordination. This limits the client’s ability to prepare food and feed themselves as well as to earn for the provision of meals. Additionally, dietary intake may be negatively affected by features of dependence and reliance on caregivers [11, 32]. Dietary modification such as textures; mechanically soft or pureed; are ideal for swallowing difficulties while nutrient dense economical meals, such as stewed legumes or low costs subprimal or retail animal, are recommended in financial resource restrictions.

Clients experiencing degenerative neurological disorders utilize higher or lower values of energy either due to the pathophysiology of the condition or the therapeutic cost of managing the condition. A personalized treatment approach is necessary dependent on the pole of the energy utilization spectrum that the client is on; higher energy intake is required in more metabolically active individuals and energy/calorie restrictions in individuals who consume or require less energy.

3. Final remarks and conclusion

Neurological degenerative disorders affect a relatively small segment of the global population but accounts for extensive disability in the affected cohort. The management of degenerative disorders has primarily surrounded pharmacotherapy, neurostimulation and gene therapy with little focus on nutritional therapy. Recent evidence suggests that this is likely due to the fact that the field of nutritional neurological research is relatively new [34]. Nevertheless, both classic and contemporary evidence points to a strong link between nutritional intake, status, and neurological health outcomes. Consequently, the management of degenerative neurological disorders should be comprehensive and include a multi-team approach. The team of health care workers who are essential to the nutritional wellbeing of clients with neurological disorders include the phlebotomist, physician, nurse, home care assistant and the dietitian. These team members must collaborate to assess, diagnose, prescribe, treat and support the nutritional needs of the ill client towards impacting his overall clinical outcome. The treatment plan is geared at client centered approach that matches nutritional interventions to the pathophysiological changes of the client with neurological disorders.

The main nutritional recommendations for the support and management of neurological disorders includes but is not limited to:

Multiteam collaborative support including a nutritionist and/or dietician to assess nutritional needs and status and create nutrition plans and interventions targeted and personalized to each client to support their recovery or prevent the occurrence. This approach ideally may reduce the course, progress, and outcome of the disease inasmuch as nutrition is employed as a therapeutic strategy. It includes the assessment of the clinical progress of the client, energy needs based on weight, physical activity and diseased state and matches the physiological needs of the client to the ideal nutrition care strategy for optimization of health. The nutrition prescriptions usually match both need for energy (from macronutrients) and the need for micronutrients.

The current evidence suggests worsening neurological decline in clients with SCA where energy and micronutrient intake may be below physiological level which negatively impacts health outcomes. This progressive decline affects dietary intake as well as nutrient requirements. A strategy to improve client overall health results is to offer healthy small packaged foods frequently especially to those exhibiting dependency and reduced appetite in order to limit dietary impact. Foods including dark chocolate, and cheeses have been found to be associated with improved neurological outcomes and meet the needs of clients who require more accessible options. Dark chocolate, in particular, has been found to improve antioxidant levels and is thought to positively affect prooxidant activities in these disorders [35].

For clients with specialized nutritional needs such as those with swallowing difficulties and increased needs for micronutrients, nutrition therapy is critical for recovery and improvement. One element of nutrition therapy is meal planning. Nutritional meal planning is an essential tool that can be utilized to support neurological health and recovery. Meal planning is a structured activity that involves forecasting and preparing nutritionally adequate meals designed to meet the dietary needs of clients. In the first instance, the principle and technique can be taught to the client by an expert and for sustained outcomes adopted and practiced by the affected clients.

The technique allows for energy balance, variety and moderation among other positive outcomes which are beneficial to mental health.

Routine biochemical assessments are essential to health maintenance and management of neurological disorders. Interventions, to be most beneficial, must be grounded in the evidence and client specific data. Biochemical tests may provide information concerning micronutrient status, deficiency or toxicities which are crucial for designing strategies to promote neuronal health and wellness and are likely risk factors in SCA with increased needs, utilization in the face of reduced intake. Some biochemical tests that may be beneficial in the assessment of SCA clients include Complete Blood Counts, Urea and Electrolyte analysis and Nutrition Panel as well as screens for other micronutrients. Results of biochemical analyses are critical for guiding the use of supplements.

Most of the plans to promote neurological health in SCA client addresses balance and increased intake but the comprehensive nutritional guide must also address targeted dietary restrictions such as energy restrictions in the face of inactivity or reduced physical activity.

Pharmacological side effects must be monitored and treated collaboratively to prevent a decline in nutritional status and the related biochemical impact in these diseases.

Finally, the group of clients affected by SCA forms a unique population of health care clients with physiological needs impacting biochemistry and functionality. These expand to present unique nutritional impact affecting status which is direct predictor of health outcomes. The management of the client with SCA must be multifaceted and incorporate nutrition as an essential therapeutic prong. The comprehensive targeted individualized nutritional support including client centered assessment, prescription, adjustment and evaluation, is the best strategy for the nutritional management of degenerative neurological disorders including SCA where the focus is on both micronutrient and macronutrient intake.