Parkinson's disease and vitamins: a focus on vitamin B12.

Parkinson's disease (PD) has been linked to a vast array of vitamins among which vitamin B12 (Vit B12) is the most relevant and often investigated specially in the context of intrajejunal levodopa infusion therapy. Vit B12 deficiency, itself, has been reported to cause acute parkinsonism. Nevertheless, concrete mechanisms through which B12 deficiency interacts with PD in terms of pathophysiology, clinical manifestation and progression remains unclear. Recent studies have suggested that Vit B12 deficiency along with the induced hyperhomocysteinemia are correlated with specific PD phenotypes characterized with early postural instability and falls and more rapid motor progression, cognitive impairment, visual hallucinations and autonomic dysfunction. Specific clinical features such as polyneuropathy have also been linked to Vit B12 deficiency specifically in context of intrajejunal levodopa therapy. In this review, we explore the link between Vit B12 and PD in terms of physiopathology regarding dysfunctional neural pathways, neuropathological processes as well as reviewing the major clinical traits of Vit B12 deficiency in PD and Levodopa-mediated neuropathy. Finally, we provide an overview of the therapeutic effect of Vit B12 supplementation in PD and posit a practical guideline for Vit B12 testing and supplementation.

Acupuncture Effect and Mechanism for Treating Pain in Patients With Parkinson's Disease.

Non-motor symptoms of Parkinson's disease (PD) have been receiving increasing attention. Approximately half of patients with PD have experience PD-related pain. We investigated the effect and mechanism of acupuncture in patients with PD who have pain. PD patients with pain were divided into acupuncture group and control group. Nine patients completed acupuncture treatment; seven patients who received only an analgesic agent underwent resting-state functional magnetic resonance imaging (rs-fMRI) twice. fMRI was performed to evaluate the functional connectivity of the brain regions. After treatment, a decrease in total scores on the King's Parkinson's Disease Pain Scale (KPPS) and Unified Parkinson's Disease Rating Scale was observed in the acupuncture group (-46.2 and -21.6%, respectively). In the acupuncture group, increased connectivity was observed in four connections, one in the left hemisphere between the middle temporal gyrus (MTG) and precentral gyrus, and three in the right hemisphere between the postcentral gyrus and precentral gyrus, supramarginal gyrus and precentral gyrus, and MTG and insular cortex. A significant correlation was noted between the changes in functional connectivity and KPPS. The involved connection was between the left middle frontal gyrus and the right precentral gyrus (R = -0.698, P = 0.037). Acupuncture could relieve pain in PD patients by modulating brain regions related to both sensory-discriminative and emotional aspects. The present study might increase the confidence of users that acupuncture is an effective and safe analgesic tool that can relieve PD-related pain.

Sleep disturbances and gastrointestinal dysfunction are associated with thalamic atrophy in Parkinson's disease.

BACKGROUND: Non-motor symptoms are common aspects of Parkinson's disease (PD) occurring even at the prodromal stage of the disease and greatly affecting the quality of life. Here, we investigated whether non-motor symptoms burden was associated with cortical thickness and subcortical nuclei volume in PD patients. METHODS: We studied 41 non-demented PD patients. Non-motor symptoms burden was assessed using the Non-Motor Symptoms Scale grading (NMSS). Cortical thickness and subcortical nuclei volume analyses were carried out using Free-Surfer. PD patients were divided into two groups according to the NMSS grading: mild to moderate (NMSS: 0-40) and severe (NMSS: ≥ 41) non-motor symptoms. RESULTS: Thalamic atrophy was associated with higher NMSQ and NMSS total scores. The non-motor symptoms that drove this correlation were sleep/fatigue and gastrointestinal tract dysfunction. We also found that PD patients with severe non-motor symptoms had significant thalamic atrophy compared to the group with mild to moderate non-motor symptoms. CONCLUSIONS: Our findings show that greater non-motor symptom burden is associated with thalamic atrophy in PD. Thalamus plays an important role in processing sensory information including visceral afferent from the gastrointestinal tract and in regulating states of sleep and wakefulness.

Perceptions of symptoms and expectations of advanced therapy for Parkinson's disease: preliminary report of a Patient-Reported Outcome tool for Advanced Parkinson's disease (PRO-APD).

BACKGROUND: What do patients expect from a treatment? A patient-centred approach to treatment is becoming necessary given the choices for invasive treatments for Parkinson's disease. Patient's perceptions of severity and expectations from complex therapies have not been studied. We describe the rationale and concept of developing a Patient-Reported Outcome (PRO) tool to assess perceptions of symptom severity and expectations of therapy. We report preliminary findings from use of the tool, association with clinical factors, and illustrate the potential use in individual patients awaiting therapy. METHODS: Patient symptoms were grouped into four domains, with 8 motor, 7 non-motor, 7 psychological and 4 social questions. For each question, symptom severity was rated on a Likert scale scoring from 0 (no problem) to 7 (perceived as a severe problem). Similarly, the expectation for each symptom to change after therapy was rated on a Likert scale: score -3 (expected to be very much worse) to + 3 (expected to be very much improved). RESULTS: 22 consecutive patients, routinely planned to receive one of Deep Brain Stimulation/Intrajejunal Levodopa Infusion/Apomorphine Infusion therapies, were recruited: 13 male, mean (+/-sd) age: 65.6 (+/-9.5) years, mean (+/-sd) disease duration: 14.3 (+/-5.7) years. Subjective severity scores are reported as mean (+/-sd) / maximum possible score: (i) motor 23.5 (+/-7.5) / 56, (ii) non-motor 15.5 (+/-5.6) / 49, (iii) cognitive - psychological 12.4 (+/-5.8) / 49, (iv) social 9.3 (+/-4.1) / 28. Expectation of change (improvement) scores are reported as mean (+/-sd) / maximum possible score of: (i) motor 14.0 (+/-5.6) / 24, (ii) non-motor 8.5 (+/-4.1) / 21, (iii) cognitive - psychological 7.4 (+/-4.4)/ 21, and (iv) social 5.5 (+/-2.8) / 12. For each domain, Spearman correlation coefficient showed significant associations between severity and expectation within-domain. CONCLUSION: This tool (PRO-APD) provides a description of perceived problem severity and expectation of treatments encompassing a holistic patient-driven view of care. PD patients about to receive complex therapy have moderately high perception of symptom load in multiple domains, and expect substantial improvements in multiple domains. These preliminary findings may be useful in documenting multi-domain symptoms, as well as counseling patients to help them reach realistic expectations and reduce potential dissatisfaction following therapy.

Narcolepsy in Parkinson's disease.

Non-motor symptoms in Parkinson's disease (PD), such as excessive daytime sleepiness, 'sleep attacks', insomnia, restless legs syndrome and rapid eye movement sleep behavior disorder, are common and provide a challenge to treatment. These sleep symptoms are also described in patients suffering from the sleep/wake disorder, narcolepsy. The International Classification of Sleep Disorders (ICSD-2) narcolepsy criteria uses a number of markers for diagnosis, of which lack or deficiency of cerebrospinal fluid (CSF) hypocretin-1 levels is a key marker. Hypocretin neurons prominently located in the lateral hypothalamus and perifornical nucleus have been proposed to interact with mechanisms involving sleep and arousal. Low hypocretin-1 levels in the CSF have been shown to correlate with hypothalamic hypocretin cell loss in narcolepsy and other forms of hypersomnia; therefore, it has been proposed that degenerative damage to hypocretin neurons (such as in PD) may be detected by low CSF hypocretin-1 concentrations, and may also explain the sleep symptoms experienced by some PD patients. To date, there is mixed conflicting data describing hypocretin-1 levels in the CSF of patients with parkinsonism associated with sleep symptoms, with most studies showing no significant decrease when compared with controls. However, hypocretin-1 CSF deficiency has been shown in some studies to be more prominent in PD patients with sleep symptoms versus those without. Notably, the hypocretin system has been shown not to be selectively disrupted, with one study showing melanin concentrating hormone cell loss in the same patients with hypocretin loss. It is likely that hypocretin deficiency in PD patients occurs secondary to collateral damage caused by the neurodegenerative process involving the hypothalamus. Awareness of narcoleptic events in PD is important for driving related advice, in addition to the possible use of dopamine D3 receptor active agonists.