Acute akinesia in Parkinson disease
Onofrj M and Thomas A;
Commented by , 20 May 2005
Background
Acute worsening of Parkinson’s disease, defined as acute akinesia, has been reported previously, but its aetiology and course had not been well elucidated.
Aim of the study
The objective of the study was to assess acute akinesia in patients with Parkinson disease. Acute akinesia was defined as a sudden deterioration in motor performance that persists for more than 48 hours despite.
Methods
This was a clinical, observational study. The study population consisted of a cohort of 675 patients followed regularly over 12 years in the authors’ own outpatient clinic. All patients were studied when acute akinesia led to hospitalization. Unified Parkinson’s Disease Rating Scale was administered during the akinetic state and compared with ratings obtained 1.6+- 0.9 months before the onset or after the recovery.
Results
All together 26 patients developed acute akinesia. In 17 of these patients new akinetic symptoms first presented at the onset of an infectious disease or after surgery, and appeared unrelated to changes in treatment or altered levodopa kinetics. In nine patients, acute akinesia developed concurrently with gastrointestinal diseases or drug manipulations and showed features of neuroleptic malignant syndrome.
The condition was severe enough to increase the UPDRS Motor Subscale score by 31.4+- 12.8 within 2 to 3 days and persisted for 11.2+- 6.2 days despite attempts to increase the dopaminergic drug dose or administer continuous subcutaneous apomorphin infusion. Symptomatic recovery began 4 to 26 days after the onset of acute akinesia and appeared incomplete in 10 patients.
Four patients out of 26 died despite treatment. Levodopa kinetics appeared to be normal in all patients without gastrointestinal disease and in one patient despite gastric stasis. The authors conclude that acute akinesia is a life-threatening complication of PD, that it does not resemble “wearing-off” which responds to dopaminergic rescue medication and may be a clinical entity distinct from other motor fluctuations.
Professor Emre's comments
Acute akinesia, sometimes also referred to, as "Parkinson crisis" is a rare, but serious complication of Parkinson disease. It was occasionally described in the context of "drug holidays" which became to be a popular intervention in the past, with an aim to "reset" the basal ganglia in secondary drug-failures, and it was the main reason why this practice was stopped (ref. 1).
This paper is an important contribution, which helps to understand the crude frequency (reported to be 0.3% per year in this study), triggering factors (infections, surgery, gastrointestinal disease, drug manipulations), possible pathophysiological mechanisms and the course of this condition.
This study demonstrated that acute akinesia may occur independently of treatment withdrawal or anti-dopaminergic drug administration, as was the case in 17 out of 26 patients. Thus, it can be differentiated from Neuroleptic Malignant Like Syndrome or Neuroleptic Malignant Syndrome (which are due to sudden withdrawal of dopaminergic medication or use of neuroleptics), as the precipitating factors are different.
The authors recognize transient refractoriness to dopaminergic rescue medication as a key element of this syndrome. They propose to redefine this condition as an "acute motor complication of PD, coincident with infectious disease, surgery, or treatment manipulations, consisting of acute worsening of parkinsonian symptoms and transient unresponsiveness to usual dopaminergic therapies or to increase in dopaminergic medication".
They further propose operational criteria consisting of "a sudden worsening of UPDRS motor score by >20 points, accompanied by >3 days of unresponsiveness to the same drug regimen that adequately corrected symptoms before or unresponsiveness to dopaminergic rescue drug administration".
These are reasonable proposals, individual items in them can be challenged, but they would at least help to an increased recognition of and research on this condition. The underlying mechanisms are unclear, but the syndrome is probably not due to problems in peripheral or central kinetics of levodopa as administration of agonists is also ineffective, at least during the acute phase.
The authors propose problems with glutamatergic or dopaminergic signal transmission through stress cascade events as a possible mechanism. As the condition can be lethal due to cardiocirculatory complications, and dopaminergic drug administration does not help, at least initially, it is recommended that systemic complications should be avoided, the treatment should consist of general measures such as rehydration, reduction of hyperthermia and removal of co-morbid factors.
Although antiparkinsonian treatments might transiently appear ineffective, delayed recovery under these treatments should encourage the physician to maintain them. Use of amantadine infusions have been proposed, it needs however, further investigation for firmer conclusions (ref. 2).
References
1. Danielczyk W. Twenty-five years of amantadine therapy in Parkinson’s disease. J Neural Transm (Suppl) 1995; 46; 399-409
2. Kornhuber J, Weller M, Riederer P. Glutamate receptor antagonists for neuroleptic malignant syndrome and akinetic hyperthermic prakinsonian crisis. J Neural Transm (Park Dis Dement Sect) 1993; 21; 393-400