Challenges Faced by Rural Health Care Providers Caring for Parkinson's Disease Patients in Neighbor Islands of Hawai'i.

When compared to their urban counterparts, rural regions have worse health outcomes and more challenges in health care access. As the only island state in the US, Hawai'i's unique geographic layout may magnify these disparities. However, there are limited publications on the impact of urban-rural disparities in health care in Hawai'i. The study team aimed to identify the challenges rural health care providers face when managing treatment of Parkinson's disease (PD), a complex disease. A self-administered survey was sent to 247 eligible providers who practiced in Hawai'i and prescribed PD medications from 2017-2019. The survey assessed: provider's comfort level in PD management; utilization and accessibility of health care services; perspective on barriers to PD care; and perspective on telemedicine. Providers were categorized into O'ahu providers (OP, urban) and neighbor island (Hawai'i, Kaua'i, and Maui) providers (NIP, rural). The final sample size was 44 providers (18% response rate). NIP were significantly less likely than OP to report access to social workers (P=.025), geriatric services (P=.001), and psychologist/psychiatrist/mental health professionals (P=.009). There were no statistical differences in: criteria used for PD diagnosis, resources utilized for PD education, and comfort in prescribing PD medications. The findings show that NIP are just as engaged and capable in providing PD care as OP. However, NIP encounter more limitations to accessibility, which can affect the quality of PD care that their rural patients receive. Further research is needed to understand how these limitations affect health-related outcomes in PD as well as other chronic diseases.

Difference in rural and urban Medicare prescription pattern for Parkinson's disease in Hawai'i.

Background: Medical management of Parkinson's Disease (PD) is becoming complex. Increasing evidence suggests that patients have better outcomes when they are managed by neurologists. However, access to neurologists can be limited in rural areas. Analysis of prescription pattern can provide insight into access gap rural patients face. Methods: This retrospective observational study used National Medicare Provider Utilization and Payment Data: Part D Prescriber Public Use Files from 2013 to 2018. Query was made for levodopa, dopamine agonists and other antiparkinsonian medications. The data elements obtained included drug name, number of prescribers, prescriber specialty, number of claims, number of standardized 30-day Part D prescriptions, and number of Medicare beneficiaries in the state of Hawai'i. Individual prescribing providers were categorized as urban or rural based on their cities of practice. Prescription patterns of urban and rural providers in Hawai'i as well as difference in provider specialty were compared, using standardized 30-day prescriptions as the primary measure of utilization. Results: Practice patterns differed between rural and urban areas. In rural Hawai'i, Rytary, Rotigoitne and selegiline were rarely prescribed. Levodopa percentage was higher in urban Hawai'i. In urban Hawai'i, 74.4% of the prescriptions were provided by movement disorders and general neurologists. In rural Hawai'i, 25.1% of the prescriptions were written by neurologists and 74.9% by general practitioners. Conclusions: In the state of Hawai'i, there is an urban-rural access gap to neurologists as evidenced by Medicare prescription pattern. Further study is needed to understand the reasons for rural-urban differences in prescription patterns and their impact on outcomes.

PET-positive extralimbic presentation of anti-glutamic acid decarboxylase antibody-associated encephalitis.

Anti-glutamic acid decarboxylase (GAD) antibody-associated autoimmune encephalitis has been reported mostly as limbic encephalitis. Only few cases with extralimbic involvement are reported with limited investigation. Here, we report an extensive investigation with MRI, PET, and pathological examination. A 66-year-old Japanese female with a history of hypothyroidism, colon cancer, pheochromocytoma, and thymoma-associated myasthenia gravis presented with generalised tonic-clonic seizures. MRI showed multiple hyperintense lesions and PET showed hypermetabolic lesions in the brain. Biopsy showed non-specific gliosis, microglial proliferation, and perivascular lymphohistiocytic infiltrates. Various neuronal antibodies were negative, except for anti-GAD antibody. Anti-GAD antibody-associated encephalitis is an increasingly recognised CNS disease. Pathophysiology of this encephalitis is unclear. While PET showed hypermetabolic lesions, the biopsy showed non-specific changes. The treatments may include immunosuppressants, IVIg, and plasma exchange. One should consider to measure this antibody, in addition to others, when autoimmune encephalitis is suspected [Published with video sequences] .

Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with infantile convulsions.

Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

Finger and face representations in the ipsilateral precentral motor areas in humans.

Several human neuroimaging studies have reported activity in the precentral gyrus (PcG) ipsilateral to the side of hand movements. This activity has been interpreted as the part of the primary motor cortex (M1) that controls bilateral or ipsilateral hand movements. To better understand hand ipsilateral-PcG activity, we performed a functional MRI experiment in eight healthy right-handed adults. Behavioral tasks involved hand or lower face movements on each side or motor imagery of the same movements. Consistent with the known M1 organization, the hand contralateral-PcG activity was centered at the "hand-knob" portion of the PcG; face contralateral-PcG activity was localized ventrolateral to it. Hand ipsilateral-PcG activity was identified in most subjects. However, converging results indicated that this ipsilateral PcG activity was situated in Brodmann's area 6 in both hemispheres. The hand ipsilateral-PcG zones were active not only during hand movements but also face movements. Moreover, the hand ipsilateral-PcG zones revealed substantial imagery-related activity, which also failed to differentiate the hand and face. Statistical analyses confirmed poor effector selectivity of the hand ipsilateral PcG activity during both movement and imagery tasks. From these results, we conclude that the hand ipsilateral-PcG activity in healthy adults probably corresponds to a part of the ventral premotor cortex. In contrast, available evidence suggests that M1 contributes to controlling the ipsilateral hand in children and patients after stroke recovery. It appears that within the human PcG, there are two parallel systems potentially capable of controlling ipsilateral hand movements: ventral premotor cortex and M1. These two systems may be differentially influenced by developmental or pathologic changes.

The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway.

Paroxysmal non-kinesigenic dyskinesia (PNKD) is characterized by spontaneous hyperkinetic attacks that are precipitated by alcohol, coffee, stress and fatigue. We report mutations in the myofibrillogenesis regulator 1 (MR-1) gene causing PNKD in 50 individuals from eight families. The mutations cause changes (Ala to Val) in the N-terminal region of two MR-1 isoforms. The MR-1L isoform is specifically expressed in brain and is localized to the cell membrane while the MR-1S isoform is ubiquitously expressed and shows diffuse cytoplasmic and nuclear localization. Bioinformatic analysis reveals that the MR-1 gene is homologous to the hydroxyacylglutathione hydrolase (HAGH) gene. HAGH functions in a pathway to detoxify methylglyoxal, a compound present in coffee and alcoholic beverages and produced as a by-product of oxidative stress. Our results suggest a mechanism whereby alcohol, coffee and stress may act as precipitants of attacks in PNKD. Stress response pathways will be important areas for elucidation of episodic disease genetics where stress is a common precipitant of many common disorders like epilepsy, migraine and cardiac arrhythmias.

Exercise-induced dystonia as a preceding symptom of familial Parkinson's disease.

Paroxysmal exercise-induced dystonia can occur with Parkinson's disease (PD), and in rare cases, this can also be the presenting symptom. We report on 2 second cousins (no known consanguinity) who presented with paroxysmal exercise-induced dystonia who later developed clinical features of PD. Although autosomal recessive inheritance was suggested, and the dystonic features further suggest parkin as a possible cause, sequencing for parkin mutations was negative and this family may represent a genetic variant of PD. Further genotype-phenotype studies in this and similar families may give clues to pre-symptomatic symptoms in PD and may reflect a particular phenotype of interest for genetics studies in the future.