Clinical study Relationship between freezing of gait (FOG) and other features of Parkinson’s: FOG is not correlated with bradykinesia A.L. Bartels 1 , Y. Balash 1 , T. Gurevich 1 , J.D. Schaafsma 1 , J.M. Hausdorff 2 , N. Giladi 1 1 Department of Neurology, Tel-Aviv University, Tel-Aviv, Israel, 2 Division on Aging, Harvard Medical School, Boston, MA, USA Summary Background: The pathophysiology of freezing of gait (FOG) is unclear. Objective: To assess the relationships between FOG and other parkinsonian features in Parkinson’s disease (PD), focusing on levodopa effects. Methods: Nineteen PD patients with significant FOG in “off” were assessed while “off” and “on”. Three observers independently viewed videotapes of a 130-m walk and scored FOG frequency. The Unified Parkinson’s disease Rating Scale was used to evaluate clinical state. Results: FOG frequency was not correlated with other parkin- sonian features in “off” and only with speech and writing in “on”. Levodopa significantly decreased FOG frequency (p < 0:001). This reduction was strongly correlated with improvement of tremor (R ¼ 0:80, p < 0:01) and speech (R ¼ 0:62, p < 0:05), but not with improvement in rigidity, bradykinesia, or balance. Conclusion: Levodopa decreases FOG in PD. FOG is apparently an independent motor symptom, caused by a paroxysmal pathology that is different from that responsible for bradykinesia, rigidity or postural instability. ª 2003 Elsevier Science Ltd. All rights reserved. Keywords: Parkinson’s disease, freezing of gait, akinesia, paroxysmal gait disorders INTRODUCTION Paroxysmal gait disturbances (PGD) are common and disabling symptoms that affect people with parkinsonism. Generally, they can be divided into sudden temporary difficulty in the initiation or continuation of walking (type 1 PGD, i.e., freezing of gait) 1–4 or sudden changes in normal locomotion rhythm (type 2 PGD, i.e., festination). 4–6 During a freezing episode (type I PGD), the patient has the feeling that both feet are suddenly glued to the ground. Typically this lasts for less than a minute and usually only for a few seconds. Freezing of gait (FOG) occurs while turning, during the initiation of gait, in narrow spaces, on reaching a destination and even spontaneously during walking in an open space. 2 FOG can often lead to falls. 1;4;7 The prevalence of FOG in Parkinson’s disease (PD) ranges from 7% in the early stages to about 60% in the more advanced stages of the disease. 3;7–9 The presence of FOG is apparently positively correlated with the duration of PD symptoms, the du- ration of levodopa therapy, disease progression as indicated by Hoehn and Yahr stage, 10 and with the akinetic-rigid form of PD. 1;9 FOG is also more common when initial motor symptoms involve gait, postural instability, bradykinesia, rigidity or speech distur- bances. 9 However, in the more advanced stage, when levodopa treatment is required, only gait and balance disturbances and speech difficulties are strongly associated with the presence of FOG. 9 Similarly, problems with the initiation of gait, falling and difficulties in turning apparently form a separate component of motor function in PD that is only weakly related to bradykinesia. 11 Despite continuous interest in FOG, its pathophysiology, its relationship to other parkinsonian symptoms, and its response to levodopa treatment remain unclear and controversial. Some have suggested that FOG is a form of akinesia (brady- kinesia/hypokinesia) and that they share a common pathophysi- ology. 11–16 Akinesia is not easy to define and controversies still exist about the meaning of this term and its pathophysiology. Akinesia has been defined as a lack of movement not caused by paralysis. 4 This would imply that akinesia can be caused by severe bradykinesia (slowness of movement) or hypokinesia (decreased amplitude of movement), by severe rigidity, or by a freezing ep- isode. The term akinesia, however, does not reflect time or du- ration; thus, it can be transient as in FOG or continuous as in bradykinesia. The actual relationship between akinesia and FOG is not clear, but in a recent prospective study there was a weak association between bradykinsia score and the presence of freez- ing of gait when assessed subjectively and qualitatively. 9 Re- search on electro-physiological aspects of FOG and on embryonic cell transplantation suggest the possibility of different pathophy- siologies in bradykinesia and FOG. 17;18 Previous studies concen- trated on the association between the presence or absence of FOG and other aspects of PD, without taking into account FOG fre- quency or severity. Lacking an objective measure, the effect of treatment on FOG has been based on the general subjective im- pression of the patients. In the present study, we objectively quantified, for the first time, the relationships between the fre- quency of FOG episodes, bradykinesia, and the severity of other parkinsonian features as well as the effects of levodopa on these parkinsonian symptoms. The relationship between levodopa treatment and FOG is complex. FOG is clearly an “off” symptom that improves with levodopa, but frequently it is seen also in the “on” state. Small numbers of patients walk better at the “off” state (early in the morning) and develop FOG only after turning “on” – “on freezers”. Our clinical experience suggests that most patients who freeze at “on” are “off” freezers who improved with levodopa but FOG persists in a milder form. The differentiation between levodopa induced “on freezing” and levodopa partially resistant “on freezing” has never been evaluated with objective measures. In the present study, we excluded those patients with levodopa induced “on freezing” (likely a minority of the Parkinson’s dis- ease patients) and concentrated on “off freezers”. As this study Journal of Clinical Neuroscience (2003) 10(5), 584–588 0967-5868/$ - see front matter ª 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0967-5868(03)00192-9 Received 16 December 2002 Accepted 4 April 2003 Correspondence to: Nir Giladi MD, Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, 6 Weizman Street, Tel-Aviv 64239, Israel. Tel.: +972-3-6974912; Fax: +972-3-6974911; E-mail: ngiladi@tasmc.health.gov.il 584