Optimizing extended-release carbidopa/levodopa in Parkinson disease: Consensus on conversion from standard therapy.

Purpose Of Review: To help clinicians optimize the conversion of a patient's Parkinson disease pharmacotherapy from immediate-release carbidopa/levodopa (IR CD/LD) to an extended-release formulation (ER CD/LD).

Recent Findings: Eleven movement disorders specialists achieved consensus positions on the modification of trial-based conversion guidelines to suit individual patients in clinical practice.

Summary: Because the pharmacokinetics of ER CD/LD differ from those of IR CD/LD, modification of dosage and dosing frequency are to be expected.

Neuropathology of non-motor features of Parkinson disease.

Non-motor manifestations of Parkinson disease (PD) are common and some may actually antedate motor dysfunction. Extrapyramidal signs in PD are tightly linked to striatonigral dopaminergic denervation associated with neuronal loss and Lewy bodies in the residual neurons of the substantia nigra. Lewy bodies composed of abnormal alpha-synuclein are the histologic hallmark of PD, and their presence beyond midbrain dopaminergic neurons is considered to be the pathologic substrate of many, if not all, of the non-motor manifestations of PD.

Comparison of risk factor profiles in incidental Lewy body disease and Parkinson disease.

Objective: To explore whether associations of potential risk factors for incidental Lewy body disease (iLBD) are similar to those for Parkinson disease (PD).

Design: Brain autopsy study (1988-2004) of subjects without evidence of neurodegenerative disease or tremor who were evaluated by at least 1 physician within 1 year of death. Researchers analyzed incidental Lewy pathology blinded to clinical abstraction.

Incidental Lewy body disease: do some cases represent a preclinical stage of dementia with Lewy bodies?

Lewy pathology occurs in 8-17% of neurologically normal people age >60, termed incidental Lewy body disease (iLBD). It is often assumed to represent preclinical Parkinson disease (PD). However, some iLBD cases have diffuse pathology inconsistent with preclinical PD.

Incidental Lewy body disease and preclinical Parkinson disease.

Background: The significance of Lewy bodies detected at autopsy in the brains of clinically normal individuals is uncertain but may represent preclinical Parkinson disease (PD).

Objective: To determine whether diminished striatal dopaminergic innervation and nigral cell loss are present in incidental Lewy body disease (iLBD), as one might expect if it is a forerunner of PD.

Design: Case-control study.

Cardiac sympathetic denervation correlates with clinical and pathologic stages of Parkinson's disease.

Attention has been drawn to cardiac sympathetic denervation in Parkinson's disease (PD) based on clinical studies using [123I] metaiodobenzylguanidine scintigraphy; however, the histologic correlates and time course of cardiac sympathetic denervation are poorly understood. To address these issues, we used tyrosine hydroxylase (TH) immunohistochemistry to detect cardiac sympathetic nerve fibers in the epicardium of 4 normal controls, 11 cases with incidental Lewy bodies (iLBs), and 14 cases of PD. Cardiac sympathetic innervation was significantly less in PD than in normal controls and cases with iLBs (P < 0.

Evidence that incidental Lewy body disease is pre-symptomatic Parkinson's disease.

Lewy bodies, the histologic hallmark of Parkinson's disease (PD), are detected in the brains of about 10% of clinically normal people over the age of 60 years. When Lewy bodies are found in normal individuals, the process is sometimes referred to as incidental Lewy body disease (iLBD). The distribution of Lewy bodies in iLBD is similar to the distribution in PD, but neuronal populations vulnerable to Lewy bodies do not show significant neuronal loss in iLBD.

Unusual compulsive behaviors primarily related to dopamine agonist therapy in Parkinson's disease and multiple system atrophy.

Unusual compulsive behaviors (weighing, card and video game playing, fishing, gardening, intense interest in established hobbies, locking and unlocking doors, repetitive dressing and undressing) occurred in relation to dopamine agonist therapy (six patients) and levodopa therapy (one patient) in seven patients with parkinsonism (seven Parkinson's disease, one multiple system atrophy). These behaviors occurred in tandem with pathological gambling, hypersexuality, compulsive eating, compulsive shopping or punding in six of the seven cases. Obsessive thoughts were present in one patient, with no prior history of obsessive-compulsive disorder.

Early-onset familial parkinsonism due to POLG mutations.

Objective: To define the molecular etiology of early-onset parkinsonism and peripheral neuropathy.

Methods: Two sisters had early-onset parkinsonism (dystonic toe curling, action tremor, masked face, bradykinesia, stooped posture, and rigidity), together with clinical and electrophysiological signs of sensorimotor axonal peripheral neuropathy.

Results: No mutations were found in the genes for parkin or PINK1.

Neurologic spectrum of chronic liver failure and basal ganglia T1 hyperintensity on magnetic resonance imaging: probable manganese neurotoxicity.

Background: An atypical form of parkinsonism has been described in patients with chronic liver disease, associated with increased T1 signal in the basal ganglia on magnetic resonance imaging. The magnetic resonance imaging signal changes are characteristic of manganese accumulation, which has been neuropathologically confirmed. Manganese neurotoxicity may result in additional neurologic findings besides parkinsonism.

Pathological hypersexuality predominantly linked to adjuvant dopamine agonist therapy in Parkinson's disease and multiple system atrophy.

Pathological hypersexuality developed in 13 patients with PD and two patients ultimately diagnosed clinically with MSA. Hypersexuality began within 8 months after starting dopamine agonist therapy in 14 of 15 cases, including four on agonist monotherapy. It resolved in the four cases where the agonist was stopped, despite continued levodopa therapy.

Alpha-synuclein immunohistochemistry in two cases of co-occurring idiopathic Parkinson's disease and motor neuron disease.

We report on two cases of sporadic idiopathic Parkinson's disease with motor neuron disease co-occurring in the same individuals. Pathological analysis revealed the presence of Lewy bodies in brainstem nuclei and basal forebrain consistent with Lewy body disease (LBD), as well as motor neuron degeneration and argyrophilic grain disease. We compared our two cases to all previously published pathological cases of combined LBD and motor neuron degeneration.

Pathological gambling caused by drugs used to treat Parkinson disease.

Background: Pathological gambling is a rare potential complication related to treatment of Parkinson disease (PD). However, the etiology of this behavior is poorly understood.

Objective: To examine the relationship between medical therapy for PD and pathological gambling.

Brain metastases.

Background: Systemic cancer is the second most common cause of death for adults in the United States. Twenty percent of these patients develop neurologic symptoms sometime during their illness. An apparent increase in the incidence of both systemic cancers and resulting brain metastases are posing an increasing challenge to health care providers.