Annals of Indian Academy of Neurology
GUIDELINES
Year
: 2011  |  Volume : 14  |  Issue : 5  |  Page : 13--15

Motor fluctuations and dyskinesias (diagnosis and management)


 

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How to cite this article:
. Motor fluctuations and dyskinesias (diagnosis and management).Ann Indian Acad Neurol 2011;14:13-15


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. Motor fluctuations and dyskinesias (diagnosis and management). Ann Indian Acad Neurol [serial online] 2011 [cited 2019 Sep 18 ];14:13-15
Available from: http://www.annalsofian.org/text.asp?2011/14/5/13/83088


Full Text

Motor complications appear in approximately 50% of patients on levodopa (LD) therapy for more than 5 years. Chase et al[1] reported that 28--84% of LD-treated patients develop motor fluctuations after an average of 4.1 years after starting LD therapy. These occur as a result of progression of the disease process (increased neuronal degeneration) and the cumulative effect of prolonged treatment with dopaminergic drugs, especially LD.

 The Motor Complications include



Motor fluctuationsWearing off effects (end-of-dose deterioration): This is the most common initial manifestation of motor fluctuation. The patient starts to feel the reappearance of motor symptoms before the next dose. It is predictable and occurs 2--4 h after a dose of LD. [2] In the initial stages, the symptoms great promptly alleviated after the same dose of dopaminergic medications. However, later the dose needs to be increased or another medicine for PD needs to be added."ON" and "OFF" phenomena which can be predictable or unpredictable : Gradually, the patient starts having "OFF" periods when not on medications or after the effect of medicine goes away, and a predictably good "ON" response about 45 min to an hour after intake of LD (or other dopaminomimetics).

However, as the disease progress, the "ON" response may be suboptimal or erratic, and patient can develop unpredictable "ON"--"OFF" motor fluctuations. These "motor shifts" occur as a result of loss of presynaptic dopamine terminals and from fluctuating neurotransmitter level. [1]Nighttime deterioration:In moderate to advanced disease, patients wake up in the night with motor symptoms, difficulty in rolling over in bed, muscular discomfort, and frequent urination.Early morning deterioration: This can often be associated with painful foot dystonia. [3]

Dyskinesias/ dystonias.These can be of the following types: [3],[4]

At peak-dose, more often dyskinesiasDuring "OFF" periods, more often dystoniasA combination of peak-dose and "OFF" period (biphasic), patients often cycling in these two phases

 Diagnosis





Diagnosis is based on meticulous history from the patient and caregivers. Patients need prolonged observation before and after a dose of medications for PD. Patients are often not concerned about the minor dyskinesias and therefore may deny this symptom. However, the caregivers are in a better position to confirm the presence of dyskinesias.When in doubt about the presence or degree of motor complications, patients should be given 24 h diaries to be completed at home, marking the OFF, ON stages, time and severity of dyskinesias, and temporal relationship with the medications. If necessary, patients and caregivers should be shown video clippings of patients with dyskinesias.Finally, patients may need a short admission in the hospital and evaluated in OFF and ON stages with UPDRS scales and scales for dyskinesias.

 Principles of Management



Suboptimal clinical response, wearing-off phenomenon, delayed "ON" or no "ON" without dyskinesias or minimal dyskinesiasOptimize the current dosage of anti-PD medications (increase the strength of each dose or give more frequently) without causing side effects.If already on optimal dosage of levodopa-carbidopa (LD) preparation only, tryadding COMT-inhibitor-entacapone (200 mg with each dose of LD, up to 1600 mg/day, [5],[6]changing over to controlled-release (CR) preparation of LD or add CR preparation to the standard LD preparation (especially a bedtime dosage of 200/50 mg CR preparation of LD for nighttime wearing-off), [7],[8]adding MAO-B inhibitor, e.g. selegiline (5 mg at morning and afternoon) or rasagiline (0.5 mg at morning, later can be increased to 1.0 mg at morning), [9]adding amantadine, 100 mg once daily, increased to twice a day, [10]adding a dopamine agonist (e.g. ropinirole or pramipexole), [3]If already on an optimal dosage of dopamine agonist only, tryswitching over to another agonist (e.g. from pramipexole to ropinirole and vice versa)adding LD preparation (immediate or CR preparation)adding MAO-B inhibitor or amantadineredistribute dietary proteinconsider surgery for PD

Nighttime deterioration: The following strategies may be tried:A CR preparation of LD at bedtimeAn extra dose of standard LD around midnight when patients wakes upAddition of dopamine agonist or entacapone if patient is not on these drugs.

Early morning deterioration: Often patients are relieved by a standard preparation of LD, which can be given crushed and with carbonated drink or on empty stomach, if patient can tolerate.

Patients with disabling dyskinesiasChoreiform dyskinesiasPeak dose dyskinesias: The following strategies can be tried:If patient is on CR preparation of LD, switch over to immediate release one [11]Reduce individual dose of LD and give more frequentIf patient is on a COMT inhibitor, stop the drugReduce the total daily dose of LD and add a dopamine agonist (ropinirole or pramipexole) or increase the dose of dopamine agonist if patient is already taking oneReduce dosage of LD and add amantadine. The dose of amantadine need to be 300-400 mg/day and the benefits tend to be short lived [12]Reduce LD and add anticholinergic drugs (e.g. trihexyphenidyl)Remove selegiline or rasagilineContinuous drug delivery such as subcutaneous apomorphine or duodenal LD may be considered [13]Atypical neuroleptics such as clozapine may be of help [14]Consider surgery for PD (deep brain stimulation of bilateral subthalamic nucleus is most preferred target) [3]

Biphasic dyskinesias: It is difficult to treat this condition, but the following strategies may be tried. [11]If patient is on a CR preparation of LD, change over to immediate release oneIncrease the total dose of LDRestrict use of LD to several early and/or mid-day dosesAdd or increase the dose of dopamine agonistubcutaneous apomorphine injections can be tried at selected timesTry continuous drug delivery (as mentioned above)Assess for psychiatric problems and treat when presentTry behavioural managementConsider surgery for PD

DystoniasPeak-dose dystoniaReduce dose of LDAdd or increase dose of dopamine agonistsConsider surgery for PDEarly-morning / OFF-period dystoniaAdd CR preparation of LD at bedtimeAdd dopamine agonist at bedtimeAdd COMT inhibitorEarly morning immediate release LD may be tried 1--2 h before getting up from bedOther drugs such as baclofen, diazepam, or anticholinergic drugs can be triedIn focal dystonia, injection of botulinum toxin type A in the dystonic muscles can be tried

Unpredictable "ON-OFF" periods: The following options may be considered.Adjust time and dose of LDAdd dopamine agonistAdd COMT inhibitorAdd rasagilineChange to liquid preparation of LD: [15]

Daily liquid preparation of LD needs to be prepared by crushing ten tablets of standard (immediate release) 100/25 levodopa/carbidopa, 2 g of ascorbic acid and dissolving in 1 L of water. This solution need to be administered every 60-90 min intervals, the dose being adjusted according to the response and side effects.Redistribute dietary proteinSubcutaneous apomorphine

Freezing (motor blocks)

Only in "OFF" state Management strategies as like in patients with wearing-offManage anxiety, if present, by appropriate drugs or behavioural therapy and nonpharmacologic techniques that involve the use of sensory or mental imagery, cues, or devices. [11],[16]Both in "OFF" and "ON" stages Increase LD to make optimal "ON"Sensory cuesAssistive devicesManage anxiety, if present, by appropriate drugs or behavioural therapyOnly "ON" freezing

It is very difficult to manage and patients sometimes benefit by reducing the dose of LD.

In summary, medical management of motor fluctuations in PD is challenging. Surgical treatment of PD may be a better option for carefully selected patients.

References

1Chase TN, Mouradian MM, Engber TM. Motor response complications and the function of striatal efferent systems. Neurology 1993;43:S23-6.
2Stern MB. Sinemet CR. Rationale and clinical experience. Neurology 1993;43:S34-5.
3Fahn S. How do you treat motor complications in Parkinson's disease: Medicine, surgery, or both? Ann Neurol 2008;64:S56- 64.
4Waters C.H. Treatment of advanced stage patients with Parkinson's disease. Parkinson Relat Disord 2002;9:15-21
5The Parkinson Study Group. Entacapone improves motor fluctuations in levodopa-treated Parkinson's disease patients. Ann Neurol 1997;42:747-55.
6Rinne UK, Larsen JP, Siden A, Worm-Petersen J; Nomecomt Study Group. Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Neurology 1998;51:1309 -14.
7Ahlskog JE, Muenter MD, McManis PG, Bell GN, Bailey PA. Controlled-release Sinemet (CR-4): A double-blind crossover study in patients with fluctuating Parkinson's disease. Mayo Clin Proc 1988;63:876-86.
8Koller WC, Pahwa R. Treating motor fluctuations with controlled release levodopa preparations. Neurology 1994;44:S23-8.
9Rascol O, Brooks DJ, Melamed E, Oertel W, Poewe W, Stocchi F, et al. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet 2005;365:947-54.
10Fahn S, Isgreen WP. Long-term evaluation of amantadine and levodopa combination in Parkinsonism by double-blind crossover analyses. Neurology 1975;25:695-700.
11Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson's disease (2001): Treatment guidelines. Neurology 2001;56:S1-88.
12Metman LV, Del Dotto P, LePoole K, Oertel W, Poewe W, Stocchi F, et al. Amantadine for levodopa-induced dyskinesias: A 1-year follow-up study. Arch Neurol 1999;56:1383-6.
13Antonini A. New strategies in motor parkinsonism. Parkinson Relat Disord 2007;13:S446-9.
14Durif F, Debilly B, Galitzky M, Morand D, Viallet F, Borg M, et al. Clozapine improves dyskinesias in Parkinson disease: A double-blind, placebo controlled study. Neurology 2004;62:381-8.
15Kurth MC, Tetrud JW, Irwin I, Lyness WH, Langston JW. Oral levodopa/carbidopa solutions versus tablets in Parkinson's disease with severe fluctuations: A pilot study. Neurology 1993;43:1036-9.
16Dietz MA, Goetz CG, Stebbins GT. Evaluation of a modified inverted walking stick as a treatment for parkinsonian freezing episodes. Mov Disord 1990;5:243-7.