Obstructive sleep apnea in Parkinson's disease patients: effect of Sinemet CR taken at bedtime.

PURPOSE: Obstructive sleep apnea (OSA) results from upper airway (UA) obstruction. In Parkinson's disease (PD), levodopa improves UA obstruction during wakefulness. We hypothesized that bedtime controlled-release levodopa (Sinemet CR) is associated with less severe OSA (lower apnea-hypopnea index [AHI]) in PD patients. METHODS: Idiopathic PD subjects underwent nocturnal polysomnography (PSG) and were divided into those taking bedtime Sinemet CR (SinCR+) and those not taking Sinemet CR (SinCR-). Outcomes were compared between groups for PSG recordings analyzed in whole and split at their mid-point with each half analyzed separately, using linear regression. RESULTS: Fifty-seven subjects were studied, eight SinCR+, and 49 SinCR-. They were 65 % male, aged 64.4 ± 10.3 years (mean ± SD), with body mass index 27.26 ± 3.98 kg/m(2). The whole night AHI was 15.6 ± 13.3 and 29.1 ± 20.8 in SinCR+ and SinCR-, respectively (p = 0.07 unadjusted, p = 0.11 adjusted for confounders). A similar trend was observed in the first half of the night. In the second half, the SinCR+ group had significantly lower AHI (beta = -18.8; p = 0.01 adjusted) and respiratory arousal index (beta = -14.2; p = 0.02 adjusted) than the SinCR- group. CONCLUSIONS: Bedtime Sinemet CR appears to reduce OSA in PD patients. There were no significant differences between groups in the first half of the night likely because of residual effects of short-acting levodopa in both groups, while Sinemet CR had residual effect in the second half. These results possibly provide an alternative to help manage OSA and improve sleep quality in PD patients.

The Use of Liquid Sinemet in Routine Clinical Practice of Advanced Parkinson's Disease: A Comparison of Available Options.

BACKGROUND: Tablet formulations of Parkinson's disease (PD) medications may become ineffective at managing motor fluctuations in advanced PD. The liquid formulation, levodopa carbidopa ascorbic acid solution, or LCAS, is an effective and inexpensive treatment for motor fluctuations however it remains underutilized. OBJECTIVE: We compared the efficacy of LCAS with tablet formulations and Duodopa jejunal infusion through routine inpatient management using hourly functional status measures, the Timed Up and Go Test (TUG). The TUG differentiates between 'off' and 'on' states and quantifies motor fluctuations. METHODS: Experienced nurses used the TUG times and functional observations recorded hourly throughout the waking day to optimize the LCAS hourly dose and the Duodopa flow rate over several days. When patients were stabilized on each of the interventions, the TUG measures were then recorded to compare the outcomes of the interventions. RESULTS: Twenty-six participants had TUG times recorded while on one or more of the formulations: 19 had TUG times recorded on tablets, 23 on LCAS and 10 on Duodopa. TUG times on LCAS and Duodopa were significantly faster compared to tablets (p < 0.0001, p = 0.001 respectively). Severity of dyskinesia was not significantly different between formulations (p = 0.35). Daily dose for the three formulations and the hourly doses for LCAS and Duodopa did not differ significantly (p = 0.37, p = 0.19 respectively). CONCLUSION: This report demonstrated the efficacy of LCAS for improving motor complications and its equivalency with Duodopa jejunal infusion.

Combination Therapy with Intravitreal Triamcinolone Acetonide and Oral Levodopa for the Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy: A Pilot Study.

Purpose: To determine the clinical effectiveness of combination therapy with intravitreal injection of triamcinolone acetonide (IVITA) and oral levodopa in eyes affected by nonarteritic anterior ischemic optic neuropathy (NAION). Methods: Longitudinal study involving 45 eyes of 45 patients with NAION who were evaluated within 14 days of NAION onset. The treatment group received an IVITA 4 mg/0.1 mL followed by 25 mg carbidopa/100 mg levodopa (Sinemet 25-100) 3 times daily for 12 weeks and the control group was untreated. Best-corrected visual acuity (BCVA) converted to logarithmic minimum angle of resolution (logMAR), visual field (VF) grades based on automated or Goldman perimetry, and mean retinal nerve fiber layer (RNFL) thickness measured on optical coherence tomography were assessed at the initial visit, 1, 3, and 6 months after NAION attack. Results: At the first visit and 6 months after NAION onset, the mean logMAR BCVA in the treatment group was significantly better than the control group (P < 0.05). BCVA was not significantly different between onset and the 6-month visit for both the control and the treatment group; however, the change in BCVA after 6 months was significantly greater in the treatment group compared with the control group (P = 0.007). Concomitant systemic disease, the changes in VF grades, and RNFL thickness from initial to 6 months after NAION onset were not significantly different between 2 groups. Conclusions: Combination therapy with IVITA and oral levodopa/carbidopa appears to be effective in the treatment of recent-onset NAION.

Refractory Seizures Secondary to Vitamin B6 Deficiency in Parkinson Disease: The Role of Carbidopa-Levodopa.

Carbidopa-levodopa has been used for more than 50 years in the treatment of Parkinson disease (PD) and other movement disorders. Pyridoxal 5'-phosphate (PLP), an active form of vitamin B6 (pyridoxine), is involved in the decarboxylation of levodopa to dopamine; carbidopa, which is combined with levodopa to reduce peripheral levodopa conversion and minimize peripheral dopamine side effects, binds irreversibly with PLP. As a result, carbidopa-levodopa may cause vitamin B6 deficiency and associated sequelae, including seizures, especially in high doses. A 78-year-old gentleman with a 6-year history of PD on carbidopa-levodopa therapy and recent weight loss presented with new-onset myoclonus and focal to bilateral tonic-clonic seizures. Workup for vascular, infectious, malignant, metabolic, and autoimmune causes of seizure was unrevealing. The folate level was critically low at <2.20 ng/dL. Video EEG studies showed moderate cerebral dysfunction and seizures with diffuse onsets. Several anti-seizure medications (ASMs) were unsuccessfully tried, so empiric treatment with high-dose steroids was initiated eventually alongside intravenous vitamin B6 therapy. Following introduction of these interventions, the patient had no further epileptic events. The vitamin B6 level came back as undetectable at <1 µg/dL. The patient was discharged to a rehabilitation center for improved strength and function. At the time of writing, he remained on two ASMs as well as IV B6 supplementation. Vitamin B6 is a required cofactor in the decarboxylation of levodopa to dopamine, and high levodopa dosages may cause B6 deficiency; in addition, carbidopa binds B6 irreversibly. We recommend screening of vitamin B6 levels in PD patients, especially those requiring high or increasing doses of carbidopa-levodopa and those with poor nutrition.

Pharmacokinetics of Rytary®, An Extended-Release Capsule Formulation of Carbidopa-Levodopa.

Parkinson's disease (PD) is a chronic progressive neurological disorder characterized by resting tremor, rigidity, bradykinesia, gait disturbance, and postural instability. Levodopa, the precursor to dopamine, coadministered with carbidopa or benserazide, aromatic amino acid decarboxylase inhibitors, is the most effective and widely used therapeutic agent in the treatment of PD. With continued levodopa treatment, a majority of patients develop motor complications such as dyskinesia and motor 'on-off' fluctuations, which are, in part, related to the fluctuations in plasma concentrations of levodopa. A new extended-release (ER) carbidopa-levodopa capsule product (also referred to as IPX066) was developed and approved in the US as Rytary® and in the EU as Numient®. The capsule formulation is designed to provide an initial rapid absorption of levodopa comparable to immediate-release (IR) carbidopa-levodopa, and to subsequently provide stable levodopa concentrations with reduced peak-to-trough excursions in plasma concentrations in order to reduce motor fluctuations associated with pulsatile stimulation of dopamine receptors and to minimize dyskinesia. Phase III studies of this ER carbidopa-levodopa capsule formulation in patients with PD have shown a significant reduction in 'off' time compared with IR carbidopa-levodopa and carbidopa-levodopa-entacapone. We present a review of the clinical pharmacokinetics and pharmacodynamics of this ER product of carbidopa-levodopa in healthy subjects and in patients with PD.

Serotonin Syndrome in Traumatic Brain Injury Patient: A case report

We report a 47-year old traumatic brain injury male patient who was treated for the rigidity and tremor with sinemet (carbidopa levodopa) and artane (trihexyphenidyl). He came to the emergency room ten days after the stopping of sinemet. Acute onset of increased obtunded, immobile, rigid, deep coma, and minimal response to a deep pain was presented. There was no evidence of the focal neurological signs. Over the next two days, he awoke with a normal mental status. His muscle tone become normal and he returned to home without residual medical problems or complications. We report a serotonin syndrome in a traumatic brain injury patient who was treated with sinemet and artane, which resulted in a dysregulation of serotonin activity.