Introduction: Bradykinesia, characterized by slowed movement, stands out as a primary symptom observed in individuals with Parkinson’s disease (PD). Nonetheless, there are instances where PD patients exhibit sudden and effective movements despite the presence of bradykinesia. This phenomenon, referred to as paradoxical kinesia, has remained a subject of interest for neuroscientists, who have struggled to unravel its underlying neural mechanisms for decades. Case Presentation: We describe a patient who is suffering from advanced PD. The patient has severe motor limitations, including difficulty rising from bed and walking, as well as cognitive decline and visual impairment. However, an interesting occurrence took place during a nightmare episode. Surprisingly, the patient was able to get out of bed and quickly run away from the perceived threat within the nightmare, without any assistance. Conclusion: This report presents the first documented case of paradoxical kinesia induced by nightmares in a patient with PD. This phenomenon raises questions about the neurological mechanisms involved, which are still not fully understood. Based on existing research conducted on both animal and human subjects, we propose that after processing the emotion of fear, the brain aversive system activates motor outputs to generate appropriate behavior. Thus, the brain aversive system converts the emotion of fear into action through projections from the inferior colliculus to motor-related areas such as the mesencephalic locomotor region, pontine nuclei, and substantia nigra.

Paradoxical kinesia is an enigmatic phenomenon initially described by Souques [1] as “a sudden and brief period of mobility typically seen in response to emotional or physical stress” in patients with advanced Parkinson’s disease (PD). Under extraordinary circumstances, incapacitated individuals can exhibit motor abilities comparable to those of healthy individuals. Another intriguing aspect is that shortly after the occurrence, the affected subjects revert to their disabled state as observed in the case of the patient described below.

We describe an 89-year-old visually impaired male, suffering from severe PD presenting tremors, severe bradykinesia with dyskinetic episodes, postural instability, freezing of gait, and cognitive decline (online suppl. Videos 1, 2; for all online suppl. material, see https://doi.org/10.1159/000539548). The patient’s Hoehn and Yahr clinical stage was V, as he was unable to get out of bed without assistance and barely able to walk (motor impairment according to the Unified Parkinson’s Disease Rating Scale part III: 75 in the OFF-state). MRI brain scans showed global atrophy including widening of the lateral ventricles and the third ventricle. Furthermore, hypointense signals on T2-weighted sequences in the left temporal lobe possibly representing granuloma or hemosiderin deposit were traceable. Such diffuse atrophy may have been reflected in reduced overall cognitive functioning (Clinical Dementia Rating CDR, score 3; online suppl. Video 2). The patient was diagnosed with PD for 5 years, receiving treatment with Levodopa.

The patient, who was sleeping alone in his bed, abruptly woke up and rushed towards the adjacent room where his wife was watching television. He swiftly sat down in a state of distress. When asked, he explained that there was a woman in the bedroom screaming at him and throwing hot oil on his face. His wife managed to calm him down by reassuring that it was just a nightmare. Once the patient regained composure, bradykinesia returned and worsened to the extent that he required assistance to stand up again and return to bed.

Occasional sleep-walking and sleep-talking may occur in PD patients with bradykinesia. However, our patient`s behavior went beyond mere walking; despite severe bradykinesia, he ran motivated by intense fear induced by the nightmare, with this ability disappearing upon calming down, suggesting the involvement of paradoxical kinesia.

Given that PD patients experience disruptions in the brain circuitry controlling movements, what enabled the ability to get up from bed without assistance and rush to the adjacent room? Bradykinesia cannot be explained by an intrinsic limitation in execution; instead, it might be a problem of scaling speed to movement distance. Bradykinesia might be a compensatory response: patients slow down because of a loss of accuracy at normal speed. PD patients move slowly when the energetic demands of a movement task increase [2]. This idea claims that (i) an implicit “choice” of slower movements rather than an inability to execute fast might explain bradykinesia, and (ii) the motor system has its own motivation circuit, which operates analogously to but separately from explicit motivation [2].

If so, it remains to be explained how paradoxical kinesia can override, even temporarily, such compensatory response or “awake” such motivational circuit. Some authors have argued that PD patients have intact motor programs but have difficulty accessing them without external sensory stimulation [3]. This hypothesis fails to account for the occurrence of paradoxical kinesia in our patient since the kinesia was likely not triggered by external sensory stimulation. Instead, it was internally initiated and driven, possibly influenced by the fear stemming from the nightmare experience. Therefore, it might be more appropriate to consider the possibility that paradoxical kinesia can be activated through some intrinsic motivational motor capacity. Nevertheless, to fully explain the case presented here we require an alternative explanation for paradoxical kinesia that does not rely on any external sensory cues. It has been suggested that in the absence of specific external sensory triggers, expectations of tight temporal constraints are sufficient to induce paradoxical kinesia [4]. As such, temporal constraints are internal events. It is also argued that aberrant basal ganglia activity entails deficits in energizing movements [2]. Despite moving slower than control subjects in tasks with increased energetic demands, PD patients exhibit a temporary shift to fast movements, accepting higher energy costs in situations where only fast movements are successful, such as waking up during a frightening nightmare. In this framework, paradoxical kinesia appears less paradoxical. That way, we might argue that such “implicit motor motivation” (i.e., outside of awareness) might be energized by urgent situations which require high costs involving relevant implicit drivers (i.e., fear induced by a nightmare or temporal constraints) or explicit stimuli [3] to elicit paradoxical kinesia.

The significant cognitive decline in our patient may be relevant since it has been argued that a potential connection between cognitive decline and paradoxical kinesia may exist [5]. It has been proposed that a “double crush” injury involving the basal ganglia and frontotemporal region may trigger paradoxical kinesia [5]. This dual damage could affect motor-control mechanisms differentially or activate alternative pathways. Indeed, activation of alternative pathways, for example involving cerebellar circuits, or of residual dopaminergic neurons (i.e., “surviving” dopaminergic neurons) in the basal ganglia, have already been proposed to explain the phenomenon of paradoxical kinesia [3, 6]. Regarding activation of residual dopaminergic neurons, studies by Anzak et al. [7], demonstrated no correlation between dopamine levels on paradoxical kinesia in humans, while Keefe et al. [8], found that blocking the dopamine system did not prevent paradoxical kinesia in rats. These studies challenge the hypothesis that paradoxical kinesia is solely driven by additional dopamine release. Thus, in searching for the neural mechanisms of paradoxical kinesia, it is crucial to identify the alternative neural pathways essential for motor control and performance that might be recruited to trigger this phenomenon.

Which brain structures might be involved in paradoxical kinesia induced by nightmares? We argue that the frightening nightmare experience might have activated structures belonging to the brain aversive system (BAS) to produce paradoxical kinesia. Indeed, emotional memories, including fear memories, are processed during REM sleep and involve interactions between the amygdala and the infralimbic medial prefrontal cortex in humans [9]. Patients undergoing stereotaxic neurosurgery reported strong feelings of fear, impending death or non-localized pain suffering caused by electrical stimulation of the inferior colliculus (IC), periaqueductal gray or amygdala [10, 11], structures which in humans and non-humans belong to the BAS. A further argument is the well-documented evidence that IC neural substrate is involved in paradoxical kinesia in rats [12] which leads us to suppose that a similar mechanism governs paradoxical kinesia in humans. After processing the emotion of fear, the BAS activates motor outputs to generate appropriate behavior. Thus, it converts the emotion of fear into action through projections from the IC to motor-related areas such as the mesencephalic locomotor region, pontine nuclei, and substantia nigra [12].

Understanding the mechanisms of paradoxical kinesia and exploring alternative strategies for locomotor activity in PD, is crucial from a clinical perspective. Despite the general effectiveness of dopaminergic drug treatment, gait deficits often persist in PD patients. Consequently, finding effective alternative approaches becomes relevant, especially considering decreased responsiveness to dopaminergic medication due to motor fluctuations or the onset of side effects after prolonged or high-dose drug intake. It is worth noting that paradoxical kinesia is not limited to aversive/threatening events. Patients can exhibit effective movements in various contexts such as kicking a ball [13], riding a bicycle [14] or dancing [15] without obvious aversive emotional triggers. Experimental studies have shown that appetitive external auditory stimulation or non-aversive electrical stimulation in the IC [12] can induce paradoxical kinesia in rats. Identifying the neural circuitry underlying paradoxical kinesia and developing long-term manipulation techniques holds promise for the improvement of therapies for the millions of individuals worldwide living with PD.

To our knowledge, this is the first documented case of paradoxical kinesia induced by a nightmare in a PD patient. Despite anecdotal evidence of paradoxical kinesia, there is a scarcity of scientific literature addressing this topic, leaving researchers and clinicians in the dark about the neural mechanisms and circuitry involved. However, our experimental studies using new animal models of paradoxical kinesia are shedding new light on the understanding of the neurophysiological mechanism underlying this phenomenon. Based on our experimental findings, we propose that when our PD patient woke up in a frightened state due to the nightmare, he may have temporarily overcome his motor deficits by activating structures responsible for processing fear-related behaviors (the BAS) bypassing defective basal ganglia circuitry. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material.

We are indebted to the patient JMN who consented to the publication of this article. We thank Lorena Thomas for editing the videos.

This study has received approval from the “Ethikkommission des Fachbereichs Humanmedizin der Philipps-Universität Marburg” (Approval No. DP_19.10.2023), demonstrating adherence to rigorous ethical standards. Written informed consent was obtained from the patient’s family (spouse) for publication of the details of their medical case and any accompanying images. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

The authors have no conflicts of interest to declare.

L.M.-T. was supported by Deutsche Forschungsgemeinschaft Grants ME4197/2 and ME4197/3.

J.G.T. and M.D.F.: clinical evaluation; D.J.P, N.C.C., and R.S. discussion, review, and critique; L.M.-T.: conception, organization, writing, and editing of final version of the manuscript.

All data generated or analyzed during this study are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.

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