Slowing Parkinson's Disease Progression with Vaccination and Other Immunotherapies.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. There are several recognized pathways leading up to dopaminergic neuron loss in the substantia nigra pars compacta and other cells in the brain as a result of age-related, genetic, environmental, and other processes. Of these, the most prominent is the role played by the protein α-synuclein, which aggregates and is the primary component of Lewy bodies, the histopathological hallmark of PD. The latest disease-modifying treatment options being investigated in PD are active and passive immunization against α-synuclein. There are currently five different monoclonal antibodies investigated as passive immunization and three drugs being studied as active immunization modalities in PD. These work through different mechanisms but with a common goal-to minimize or prevent α-synuclein-driven neurotoxicity by reducing α-synuclein synthesis, increasing α-synuclein degradation, and preventing aggregation and propagation from cell to cell. These promising strategies, along with other potential therapies, may favorably alter disease progression in PD.

Apraclonidine in the treatment of ptosis.

Transient ptosis is a known complication of botulinum toxin (BoNT) injection due to inadvertent migration of toxin into the levator palpebrae superioris muscle. Currently there is no treatment available for BoNT induced ptosis. Apraclonidine hydrochloride is a topical ophthalmic solution with selective alpha-2 and weak alpha-1 receptor agonist activity that has the ability to elevate the eye lid. Apraclonidine has been used as a diagnostic test in Horner's syndrome. We evaluated the effects apraclonidine in a cohort of BoNT induced ptosis and a patient with Horner syndrome. Each patient was administered 2 drops of apraclonidine 0.5% solution to the eye with the ptosis and was re-examined 20-30min later. All 6 patients showed improvement in ptosis. There was also improvement in ptosis in a patient with Horner's syndrome. Apraclonidine is not only useful as a diagnostic test in Horner's syndrome, but may be an effective and safe treatment for BoNT-induced ptosis.

Treatment of blepharospasm with apraclonidine.

OBJECTIVE: To describe improvement in blepharospasm with apraclonidine. BACKGROUND: Blepharospasm is a focal dystonia involving chiefly the orbicularis oculi and periocular muscles resulting in involuntary sustained eyelid closure. Botulinum toxin injection is the mainstay of treatment with meaningful improvement in over 85% of patients, but the effects often wear off within 3-4months. Apraclonidine is an alpha-2 adrenergic receptor agonist, which causes contraction of superior tarsal (Müller) muscle which may improve blepharospasm-related eyelid closure. We propose that apraclonidine may be a useful short-term treatment in patients with blepharospasm, particularly during wearing off from botulinum toxin injection. METHODS: Patients who had pre-mature wearing off of botulinum injection effect were evaluated before and after the administration of 2 drops of apraclonidine 0.5%-1% solution to each eye. Subjective patient impressions and examiner's impression of symptoms pre and post-apraclonidine administration were recorded. A blinded rater evaluated the videos and provided an independent assessment of the severity of symptoms pre- and post-administration, using a 0-4 scale. RESULTS: Our study included 7 patients (4 male) with a mean age of 61years and mean duration of blepharospasm of 3.6years. There was a subjective, albeit transient (about 2-4h) improvement in blepharospasm reported by all patients and by the examiner. The mean severity scores, based on blinded video ratings, showed a reduction from of 3.4 pre-administration to 2.3 post-administration of apraclonidine (p<0.025). No adverse effects were noted. CONCLUSIONS: Apraclonidine is a potentially useful medication for short term management of blepharospasm symptoms while awaiting botulinum toxin injection.

Drug-Induced Dyskinesia, Part 2: Treatment of Tardive Dyskinesia.

Dyskinesias encompass a variety of different hyperkinetic phenomenologies, particularly chorea, dystonia, stereotypies, and akathisia. The main types of drug-induced dyskinesias include levodopa-induced dyskinesia (LID) in patients with Parkinson's disease and tardive syndrome (TS), typically present in patients with psychiatric or gastrointenstinal disorders treated with dopamine receptor blocking drugs, also referred to as neuroleptics. Besides preventive measures (i.e., avoiding the use of the offending drugs), general treatment strategies include slow taper of the offending agent and use of dopamine-depleting agents like tetrabenazine. Botulinum toxin may be helpful for wearing off focal dystonia and some forms of tardive dystonia. Deep brain stimulation is usually reserved for patients with disabling motor fluctuations, LID, and for severe TS that cannot be managed medically.

Drug-Induced Dyskinesia, Part 1: Treatment of Levodopa-Induced Dyskinesia.

Dyskinesias encompass a variety of different hyperkinetic phenomenologies, particularly chorea, dystonia, stereotypies, and akathisia. Levodopa-induced dyskinesia (LID) is one of the main types of drug-induced dyskinesia, occurring in patients with Parkinson's disease (PD) who have been treated with levodopa for long time, but this side effect may be encountered even within a few weeks or months after initiation of levodopa therapy. Based on the temporal pattern in relationship to levodopa dosing, LIDs are divided into "peak-dose dyskinesia," "diphasic dyskinesia," and "wearing off" or "off-period" dyskinesia, of which peak-dose dyskinesia is the most common, followed by off-period, and then diphasic dyskinesia. Treatment strategy includes identifying the kind of dyskinesia and tailoring treatment accordingly. Peak-dose dyskinesia is treated mainly by reducing individual doses of levodopa and adding amantadine and dopamine agonists, whereas off-period dystonia often responds to baclofen and botulinum toxin injections. Diphasic dyskinesias, occurring particularly in patients with young-onset PD, are the most difficult to treat. While fractionation of levodopa dosage is the most frequently utilized strategy, many patients require deep brain stimulation to control their troublesome motor fluctuations and LIDs. A variety of emerging (experimental) drugs currently in development promise to provide better control of LIDs and other levodopa-related complications in the near future.