Freezing of gait: moving forward on a mysterious clinical phenomenon

Abstract

Freezing of gait (FoG) is a unique and disabling clinical phenomenon characterised by brief episodes of inability to step or by extremely short steps that typically occur on initiating gait or on turning while walking. Patients with FoG, which is a feature of parkinsonian syndromes, show variability in gait metrics between FoG episodes and a substantial reduction in step length with frequent trembling of the legs during FoG episodes. Physiological, functional imaging, and clinical-pathological studies point to disturbances in frontal cortical regions, the basal ganglia, and the midbrain locomotor region as the probable origins of FoG. Medications, deep brain stimulation, and rehabilitation techniques can alleviate symptoms of FoG in some patients, but these treatments lack efficacy in patients with advanced FoG. A better understanding of the phenomenon is needed to aid the development of effective therapeutic strategies.

Conflict of interest statement

Conflicts of interest

In the past 3 years, JGN and the Oregon Health & Sciences University (OHSU) have received consulting fees from Xenoport, Impax Laboratories, Neurogen, Synosia, Neuroderm, Merck, Lilly/Medtronics, Elan, Addex, Lumbeck, Merz Pharmaceuticals, and SynAgile, and grants from the National Institutes of Health (NIH), the Veterans Administration, the National Parkinson Foundation, the Michael J Fox Foundation, the RJG Foundation, and Merck. In the past 3 years, BRB and the Radboud University Nijmegen Medical Centre have received consulting fees, travel funds, board membership fees, and grants from Boehringer Ingelheim, Teva, GlaxoSmithKline, Novartis, the Movement Disorder Society, the European Federation of Neurological Societies, Tijdschrift voor Neurolgie en Neurochiugie, the Netherlands Organisation for Scientific Research, the Michael J Fox Foundation, Prinses Beatrix Fonds, Stichting Intemationaal Parkinson Fonds, and the van Alkemade-Keuls Foundation. In the past 3 years, NG and the Sackler School of Medicine, Tel Aviv University, have received board membership fees, consulting fees, speaking fees, travel fees, and grants from the Movement Disorder Society, Teva, UCB, Schwarz Pharma, Lundbeck, Eisai, Intec Pharma, GlaxoSmithKline, Solvay, Merz, Biogen, Neuroderm, the Michael J Fox Foundation, the National Parkinson Foundation, and the Israel Science Foundation. In the past 3 years, FBH and the OHSU have received speaker fees, board membership fees, and grants from the Hong Kong Polytechnical University, the APDM Inc OHSU Hospital Innovation Fund, and NIH, MH and AN declare that they have no conflicts of interest.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Figures

Figure 1:. Illustration of FoG in a patient with Parkinson’s disease

The tracing shows the angular displacement of the knees (% maximum knee angle) measured with an eight-camera Vicon optical motion capture system during a gait trial with FoG. The gait cycles before the freezing episode show a progressive decrement of step length as indicated by the dashed arrows. During the episode of FoG, irregular, rapid knee trembling is apparent. FoG=freezing of gait.

Figure 2:. Example of freezing during repetitive finger movement

The angular displacement of alternating right and left finger flexion (% maximum flexion angle) measured with potentiometers placed on the fingers is shown during atrial with upper-limb freezing. The disturbance of the regular motion preceding the freezing episodes is characterised by amplitude regression as indicated by the dashed arrows. During the episode, irregular finger trembling is apparent.

Figure 3:. CNS circuitry controlling locomotion and balance

5-HT=serotonin. ACh=acetylcholine. CN=cuneiform nucleus. CPG=central pattern generator. DA=dopamine. Glu=glutamate. MLR= mesencephalic locomotor region. NA=noradrenaline. PPN=pedunculopontine nucleus. PMRF=pontomedullary reticular formation. SCN=subcuneiform nucleus.

Figure 4:. Knee trembling when attempting to initiate a step in a patient with Parkinson’s disease and freezing of gait

The vertical forces, measured with force plates under each foot, shows repeated lateral weight shifting and reciprocal activation of left and right hip abductors, the tensor fasciae latae (TFL) muscles, measured with surface EMG. The pattern resembles repeated anticipatory postural adjustments (APAs) that normally occur only once to unload the stepping leg. The first vertical line is at the onset of the APA and the second line is at the onset of the step. Reproduced from Jacobs and colleagues, by permission of Elsevier.