Faculty Bibliography

Objective: 1) To demonstrate the feasibility of an interdisciplinary home visit program (HVP) for advanced Parkinson's disease (PD) providing expert, interdisciplinary care directly to homebound patients; 2) to test whether the HVP improves patient quality of life despite disease progression. Background: As PD progresses, symptoms increase, quality of life declines, and individuals may become homebound, often losing access to neurologic care. This leads to a surge in emergency department visits and hospitalizations. Improving access to expert in-home care may improve quality of life. Design/Methods: PD patients meeting Medicare criteria for homebound status are eligible to receive quarterly home visits over 12 months. Each visit entails an evaluation by a movement disorders specialist, social worker, and nurse, including detailed history, physical examination, real-time medication reconciliation, psychosocial evaluation, and referral to in-home services. Quality of life (Neuro-QoL) is measured at Visits 1 and 4. Results: Out of 27 subjects enrolled, 26 have completed the study. At baseline, subjects' mean age is 81 years (SD 7.8); mean PD duration is 10 years; mean UPDRS total score is 65 (SD 20). Of the 26 subjects completing Visit 4, total UPDRS increased by a mean of 12 (SD 10.7), yet quality of life improved in 7/8 Neuro-QoL domains. Conclusions: We identified a unique population typically lost to clinical care and research-the elderly, homebound with advanced PD-and this is the first description of their progression over time. Despite the expected progression of functional and motor disability over one year, subjects reported improved quality of life since entering the HVP. Next steps include the implementation of a hybrid in-person/telehealth home visit model, inclusion of individuals with cognitive impairment in future studies, and comparison of outcomes with other advanced PD populations

Parkinson disease (PD) is a common progressive neurodegenerative condition, causing both motor and non motor symptoms. Motor symptoms include stiffness, slowness, rest tremor and poor postural reflexes, whereas nonmotor symptoms include abnormalities of mood, cognition, sleep and autonomic function. Affected patients show cell loss in the substantia nigra pars compacta, and accumulation of aggregated alpha-synuclein into intracellular structures called Lewy bodies, within specific brain regions. The main known non modifiable risk factor is age. The neuroepidemiology of PD is complex with susceptibility genes and a number of modifiable risk factors that can increase and others that can mitigate risk and outcome.

A 25-year-old right-handed male presented with head and bilateral arm and leg tremor. His symptoms began at age 10 years with action tremor of both hands and progressed in severity with time. He had difficulty with social interactions but did not have intellectual disabilities. His past medical history was significant for obsessive compulsive disorder and anxiety, asthma, gastroesophageal reflux disease, and scoliosis; and his family history was significant for tremor in his father and paternal grandfather. Genetic testing was performed and identified a deleterious sequence variation in exon 19 of the calmodulin-binding transcription activator 1 (CAMTA1) gene. The presence of this sequence variation was confirmed in the patient and in his affected father. The case is novel because of tremor predominance and because the mutation is a sequence variation rather than a deletion or duplication.

Objective: Mutations of the CAMTA1 (calmodulin-binding transcription activator 1) gene have been reported in a few families in the medical literature. Phenotypic presentations associated with this autosomal dominant syndrome include intellectual disability (ID), non-progressive cerebellar ataxia, and neurobehavioral abnormalities. We report a patient with a novel nonsense mutation of the CAMTA1 gene, who presents with a novel tremor predominant phenotype. Methods: A 25-year-old right handed male patient presented with a history of head and bilateral arm tremor, since age 10. Past medical history was significant for obsessive compulsive disorder, anxiety, asthma, GERD and osteoarthritis. Family history was significant for tremor in father and paternal grandfather. A presumed diagnosis of essential tremor was made and propranolol, primidone and topirimate were tried without any benefit. Results: Extensive blood work was normal. MRI brain did not show any cerebral or cerebellar atrophy. Whole mitochondrial genome sequencing demonstrated only 1 variant of unknown significance. Whole exome sequencing (WES) revealed a novel predicted deleterious sequence variation in exon 19 of the CAMTA1 gene leading to the introduction of a stop codon at position 1541 (c.4621C>T, pR1541). The presence of this mutation was confirmed in the patient and his affected father by Sanger sequencing. Conclusion: This report expands the known phenotypic expressions of the CAMTA1 gene to include tremor predominance and is the first report of a nonsense mutation in this gene. This mutation may explain some cases of presumed essential tremor in the correct clinical context

Objective: Epilepsy is not a common co-morbidity of Parkinson's disease (PD). We report a case series of individuals with coexisting PD and epilepsy. Methods: Among the 1,200 patients with idiopathic PD at our institution, we identified seven with coexisting idiopathic seizure disorder. Subjects with documented or suspected secondary epilepsy were not included in this report. We could not obtain full clinical information on seizure history on one subject who was therefore excluded. Results: Of the 6 subjects included (3 Men, 3 Women; Ages 49-85; PD disease duration 1-15 years), 2 had seizures after PD onset (10 and 7 years after PD onset), 3 had adult-onset seizures before PD (6, 14, and 15 years before PD onset), and 1 subject had pediatric-onset seizures before PD (age 13). Three subjects had complex partial seizures, one of whomdeveloped 2 secondary generalized seizures, and three subjects had simple partial seizures. At last observation, one subject was H&Y stage 4, one was 2.5, three were 2, and one was 1. Based on UPDRS-I, 2 subjects exhibited mild cognitive impairment, 2 had moderate impairment, and 2 had no impairment. Conclusions: Although rare, epilepsy can coexist with PD. While this may be a chance association, it is possible that abnormal intracortical excitability in PD[1] may predispose patients to seizures. This limited data also suggests that patients with coexisting epilepsy may be at higher risk of developing cognitive impairment

Objective: 1) To demonstrate the feasibility of an interdisciplinary home visit program (HVP) for advanced Parkinson's Disease (PD) providing expert, interdisciplinary care directly to homebound patients; 2) to test whether the HVP improves patient quality of life despite disease progression. Background: As PD progresses, symptoms increase, quality of life declines, and individuals may lose access to neurologic care, becoming homebound. This leads to a surge in emergency department visits and hospitalizations. Improving access to expert in-home care may improve quality of life and minimize acute healthcare utilization. Methods: PD patients treated at The Fresco Institute for Parkinson's and Movement Disorders who meet Medicare criteria for homebound status are eligible to receive four quarterly home visits over 12 months. Each visit entails an evaluation by a movement disorders specialist, social worker, and nurse, including detailed history of symptoms, falls, and healthcare utilization; physical examination including the UPDRS; medication reconciliation; psychosocial evaluation and follow-up; and referral to in-home services. Quality of life (Neuro-QoL) is measured at Visits 1 and 4. Results: We have enrolled 26 subjects to date; 65% have completed 3 and 38% have completed 4 visits. At baseline, subjects' mean age is 81 years (SD 8); mean PD duration is 10 years (SD 6); mean UPDRS total score is 65 (SD 20, range 35-107). In the 12 months prior to enrollment, 48% had been hospitalized; 40% had visited an ED. Of the 10 subjects completing Visit 4, total UPDRS increased by a mean of 13 (SD 9), yet quality of life improved in 9/9 Neuro-QoL domains. Preliminary analysis of the first 74 visits shows no change in the rate of acute healthcare utilization between the 12 months preceding and time since HVP entry (p=0.59). Conclusions: Despite the expected progression of functional and motor disability over one year, subjects report improved quality of life since entering the HVP. No difference in acute healthcare utilization has yet been observed. We are in the process of assessing medication errors, adherence, and caregiver strain in this understudied population, with the aim of expanding the HVP as a novel model of care in the future. Previously Presented: The design and interim analysis of the HVP model was previously presented at the International Congress of Parkinson's and Movement Disorders 2015 and 2016, respectively

Objective: To compare changes in clinical outcomes after weekly low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) sessions over one vs. two pre-motor cortex (preMC) areas in Parkinson's disease (PD). Background: The preMC is a key component in the complex system responsible for motor execution. Particularly, dorsal preMC (PMd) and supplementary motor area (SMA) are critically involved in PD pathogenesis due to their broad anatomical and functional connectivity with the basal ganglia and motor cortex (Buhmann et al, 2004; Shirota et al, 2013). Weekly rTMS over SMA has been determined as an effective add-on therapy for PD motor symptoms (Shirota et al, 2013). Nevertheless, the therapeutic potential of combining different premotor targets has never been tested. We designed an active controlled study to explore potential additive effects of rTMS over both SMA and PMd as compared to SMA alone. Methods: Eighteen PD patients with H&Y scores 2 and 3 participated in a parallel double-blind randomized study of four weekly sessions of LF rTMS. Outcomes were assessed at baseline and 4 weeks post-treatment completion. Stimulation arms were rTMS over SMA or rTMS over both PMd and SMA (PMd+SMA). Clinical outcomes were total UPDRS-III and axial, tremor, rigidity, and bradykinesia subsets during ON time. Results: Baseline demographic and clinical characteristics did not differ between groups. Fourteen patients, 6 SMA-alone and 8 PMd+SMA, completed all study visits. Both interventions, SMAalone and PMd+SMA, significantly decreased UPDRS-III (z=-2.21, p=0.027; z=-2.53, p=0.011, respectively). Subset analyses showed SMA-alone significantly decreased only bradykinesia subset (z=- 2.21, p=0.027) while PMd+SMA decreased both bradykinesia and axial subsets (AxS) (z=-1.98, p=0.048; z=-2.39, p=0.017, respectively). Comparison between arms showed that only PMd+SMA significantly improved AxS (U=5.5, p=0.013). [figure1] There were no significant differences in changes in total UPDRS-III or any other subset. Conclusions: Both rTMS interventions were well-tolerated and improved UPDRS-III total motor scores and bradykinesia. However, improvement in AxS was seen only in the PMd+SMA group, suggesting that LF rTMS over combined preMC areas could be an effective therapy to improve axial symptoms. Larger placebocontrolled studies need to be conducted to corroborate these findings. (Figure presented)

Background: Medication errors including non-adherence are independently associated with increased morbidity and mortality in the elderly population. In the USA, medication errors are estimated to increase healthcare costs by over $170 billion annually. In Parkinson's disease (PD) specifically, medication non-adherence directly increases disability and healthcare costs. When PD progresses and patients become homebound, office-based medication reconciliation is not possible and errors may go undetected. Objectives: To examine the number and types of medication errors detected by a registered nurse during interdisciplinary home visits for patients with advanced PD. Methods: We defined medication discrepancy errors as errors of dose, frequency, strength, omission, and commission. We compared provider-documented prescriptions with the patient- or caregiver- administered regimen for 26 subjects completing at least one home visit (and up to 4) during a one-year period of quarterly home visits. Results: Among 26 subjects, 11 subjects (42.3%) had completed four visits. In total, 54 errors were detected across 78 visits (0.69 detected errors per visit), with a median of 1 error per subject (range 0-9). The most common types of detected errors were errors of commission (35%) in which the subject was taking a medication not known to the provider or which they were instructed to discontinue, followed by errors of frequency (28%) and omission (24%). Conclusion: Medication errors are frequent among advanced PD patients and are ongoing even with medication reconciliation efforts. To our knowledge, this is the first study documenting the prevalence of medication errors in homebound patients with advanced PD and supports the value of a home visit program in advanced PD. This abstract has previously been presented at the 20th International Congress of Parkinson's and Movement Disorders on June 20th, 2016