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A case of painful legs and moving toes syndrome mimicking somatic symptom disorder

Psychogeriatrics2024Vol. 24(4), pp. 1023–1029

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Yu Mimura, Kimiko Komatsu, Yohei Yasushi, Morinobu Seki, Shinichiro Nakajima, Hiroyuki Uchida, Masaru Mimura

Abstract

Painful legs and moving toes syndrome (PLMT) is a rare disorder characterized by pain in one or more lower extremities accompanied by involuntary movements. Since the first case report, subsequent larger cohort studies have refined the symptoms in greater detail.1, 2 These studies indicate that PLMT predominantly affects middle-aged females, with most patients reporting pain prior to the onset of involuntary movements.1, 2 The pain associated with PLMT manifests in various forms including tingling, numbness, and aching.1 Typically, the involuntary movements comprise a combination of flexion/extension, abduction/adduction, and wriggling/dystonia/writhing.1 While no definitive biomarkers have been established for the PLMT diagnosis, neurophysiological and functional studies such as electromyography (EMG), somatosensory evoked potentials (SSEP), and single-photon emission computed tomography (SPECT) have been proposed as potential diagnostic tools.1, 2 Conversely, magnetic resonance imaging (MRI) of the brain and spinal cord is typically within normal limits in most cases of PLMT, suggesting that PLMT may be a functional disorder.1 The pathophysiology of PLMT remains incompletely understood; however, several hypotheses have been proposed: (1) damage to peripheral nerves or nerve roots due to trauma, autoimmune processes, or neurodegeneration; (2) functional alterations in afferent input to the brainstem and subcortical areas; (3) subsequent remodelling of the central nervous system, leading to dysfunctions within the pain matrix, and (4) ultimately resulting in excitatory and inhibitory imbalances in lower motor neurons. Many patients with PLMT experience misdiagnoses. Patients often describe their pain with terms like ‘electricity’, ‘crawling’, and ‘vibrations’, which can lead clinicians to inadvertently misdiagnose PLMT as a psychiatric disorder. The absence of consensus on diagnostic criteria further exacerbates the risk of underdiagnosis. This case report presents a patient with PLMT who was previously misdiagnosed with somatic symptom disorder. Sustained improvement was observed in the patient following pharmacotherapy that included mirogabalin. Strategies to ensure accurate diagnosis and effective management are discussed. A female patient in her 70s experienced chronic genital pain following herpes zoster infection in September X – 6 (where X is the year of admission to our hospital), necessitating a psychiatric consultation in February X − 5. Initially, she showed mild depression and sulpiride was prescribed. Sulpiride was promptly discontinued due to the onset of tremor, raising concern for a manifestation of Parkinson's disease (PD), as the tremor persisted after discontinuation. In June X − 5, she developed back stiffness after overhearing a conversation about similar symptoms. Her psychiatrist noted her suggestible personality. Despite normal lumbar MRI results from year X − 4 to X − 2, she used a cane to walk. By September X − 2, psychotherapy had eliminated her genital pain and the need for a cane. However, in March X − 1, her back stiffness returned, accompanied by new left toe pain and right lateral body flexion. Pregabalin and clonazepam were prescribed for her pain and stiffness, respectively; however, pregabalin was soon discontinued due to dizziness without effect. Mirtazapine was prescribed for her depressed mood and insomnia. Over the next year, her symptoms worsened, and she started to notice involuntary movements in both toes. In March X, a neurologist suspected PD, and she was started on levodopa (200 mg/day). Her primary psychiatrist diagnosed her persistent pain as a somatic symptom disorder; however, due to the persistence and progression of her symptoms, especially the extreme pain, she was admitted to our hospital for a thorough evaluation. On admission, general physical examinations were unremarkable. Neurological examinations revealed the following. She was awake and alert. She had no obvious aphasia or apraxia. She did not complain of constipation, urinary urgency, dizziness, or decreased sense of smell. Cranial nerve examinations were unremarkable. There was no evidence of paralysis, and bilateral reflexes were within normal limits. Fine tremor (4–5 Hz) of the fingers (bilateral and left dominant) was noted, but no apparent recurrent, action, or intention tremor were noted. Finger-nose-finger test and diadochokinesia were within normal limits. Mild rigidity of the left elbow and wrist was present. She walked slowly with a cane, but there was no evidence of gait freezing. She described pain in her left toe as if it was being pulled from inside her body. She felt pain from the toe to the thigh, predominantly on the left, with a tingling quality. On the Numeric Rating Scale (NRS) for pain (10 being maximum, 1 being minimum) she rated 9/10 supine, 7/10 sitting, and 1/10 standing and walking. Toes of both feet (right dominant) opened and extended involuntarily. She exhibited mild depressive mood in response to persistent pain; however, she did not exhibit sleep disturbance, appetite loss, agitation, delusions, hallucinations, or suicidal ideation. Her medications included mirtazapine 7.5 mg/day, clonazepam 0.5 mg/day, and levodopa 200 mg/day. Head MRI showed no abnormal findings. With regard to biomarkers of PD, a dopamine transporter scan showed decreased uptake bilaterally, and metaiodobenzylguanidine myocardial scintigraphy showed a lower delayed-phase heart/mediastinum ratio of 2.15 and an increased washout ratio of 55.4% (Fig. 1). SPECT imaging found right dominant decreased blood flow in the parietal cortex (Fig. 2). There were no abnormal SSEP findings. Lumbar MRI showed spinal canal stenosis from L2/3 to L4/5 (Fig. 3). Given these findings, a diagnosis of somatic symptom disorder was ruled out because we could not identify any disproportionate thoughts, fears, or concerns on the part of the patient regarding her symptoms. A neurologist's suggestions were as follows.1 She could be diagnosed with a clinically probable PD based on the Movement Disorder Society criteria.2, 3 Her primary complaint was pain, rather than tremor, rigidity, or stiffness, a pain-focused medication regimen. Therefore, a pain-focused medication regimen based on a diagnosis of PLMT was suggested.3 In addition, neurological examinations suggested her stiffness in the back was not due to dystonia, but possibly induced by scoliosis and spinal canal stenosis. After discussion, levodopa was increased to 300 mg/day for bradykinesia and clonazepam to 1 mg for back stiffness. Trihexyphenidyl was initiated from 0.5 mg/day for left finger tremor. Mirogabalin was initiated from 5 mg/day and increased to 20 mg/day for left toe pain. Mirogabalin gradually improved the pain in her left toe to an NRS score of 2–3/10 with no side effects. The patient, her family members and our team shared the hypothesized pathophysiology behind her symptoms (Fig. 4). Over 4 years of outpatient follow-up, her motor symptoms remained stable on unchanged doses of levodopa and trihexyphenidyl. After discharge, her improved mood allowed her to discontinue mirtazapine. Clonazepam effectively controlled her stiffness and right side flexion problems. Follow-up imaging showed mild progression of PD markers. Pain was well controlled with 20–30 mg/day of mirogabalin, although not completely resolved, and involuntary toe movements continued but did not affect her quality of life (Fig. 5 and Movie S1). The patient with PLMT, who was initially misdiagnosed as having a somatic symptom disorder, showed a continuous response to pharmacotherapy that included anti-Parkinson medications combined with mirogabalin, as demonstrated in this case report. This is the first case report describing the potential efficacy of mirogabalin in improving pain in a patient with PLMT. Several pitfalls have to be acknowledged by clinicians to accurately diagnose prospective cases of PLMT. Primarily, a history of psychiatric disorders does not necessarily imply that current symptoms are induced by psychogenic processes. The present case, characterized by a suggestible personality and a history of favourable response to psychotherapy, could lead to a misdiagnosis as a psychiatric disorder. Additionally, descriptions of sensations such as ‘being pulled from inside of the body by someone else’ may prompt clinicians to suspect psychiatric disorders. However, according to previous case series, conditions such as depression and suicidal attempts are concurrent with PLMT, indicating that psychiatric disorders are prevalent comorbidities associated with PLMT.1, 2 It is crucial for clinicians to recognize that while ‘pulling’ is not a typical description of pain, 3 out of 76 patients in a study described their pain as ‘pulling’.1 Secondly, the results of neurological examinations in patients with PLMT are widely different among individuals. Previous reports indicate that 21% of patients exhibited no abnormal findings, while others presented with a range of symptoms including sensory peripheral neuropathy, reduced or absent reflexes, mild distal limb weakness, hyperreflexia, and impaired rapid alternating movements—all of which were absent in the present case.1 Additionally, tremors at rest and comorbidities with PD are rarely observed in patients with PLMT.1, 2 Given the prevalent underdiagnosis of PLMT, our case may exemplify a variant course of PD in which symptoms are masked by pain and involuntary movements as symptoms of PLMT. Lastly, no established biomarker has yet been identified for PLMT. The majority of PLMT patients exhibit negative neuroimaging results for the brain and spinal cord. Notably, only one participant in the study by Nishioka et al.2 had lumbar canal stenosis at the L2/3 levels, like the present case, suggesting that central nervous system damage alone cannot account for the symptoms of PLMT. Conversely, functional studies may provide insight into the pathophysiology of PLMT. EMG has revealed mild abnormalities in nearly half of the patients, including radiculopathy, peripheral neuropathy, fasciculations, and irregular phasic bursts of varying duration and frequencies associated with co-contraction in some PLMT patients.1, 2 Although brain and spinal MRI often show normal findings, some patients exhibit abnormal SSEP, suggesting possible impairment of the central sensory integrating systems; however, these results are inconsistent. In our case, the SSEP results were normal. A recent study has revealed that SPECT imaging shows varied perfusion patterns in brain regions associated with the pain matrix, a network implicated in multiple dimensions of pain perception. Despite these findings, our presented case did not exhibit hyper- or hypoperfusion patterns in pain matrix. In summary, clinicians can draw three main instructions from this case report to avoid misdiagnosing PLMT as psychiatric conditions. First, an accurate diagnosis requires a precise understanding of the typical presentation of PLMT. When middle-aged female patients present with lower extremity pain accompanied or followed by involuntary movements, considering the possibility of PLMT may help to make an accurate diagnosis. In addition, clinicians should not attribute atypical pain descriptions, such as tingling and crawling, to psychogenic processes alone. Second, diagnosis based on pain ratings has inherent difficulties due to the reliance on subjective patient reporting, which contributes to the frequent misdiagnosis of underlying conditions such as fibromyalgia. In PLMT, pain is primarily localized in the lower legs and toes, with the presence of involuntary movements serving as crucial diagnostic indicators, as objectively demonstrated in the presented case (see video). Third, the absence of imaging abnormalities does not imply psychiatric conditions. The pathophysiology of PLMT involves functional changes in the nervous system; therefore, not all patients with PLMT will have abnormal findings on clinical imaging studies. While functional studies such as EMG and SPECT may provide insight in certain cases, the diagnosis should be based primarily on clinical history and the identification of persistent pain and involuntary movements. Alleviation of pain soon after the initiation of mirogabalin suggests its potential as a viable treatment option for patients with PLMT. Typically, these patients find the associated pain to be more treatment-resistant and distressing than the involuntary movements. While pregabalin is known to alleviate neuropathic pain, it is also associated with a higher incidence of somnolence and dizziness compared to mirogabalin.4 Mirogabalin demonstrates its analgesic effect by selectively binding to the α2δ-1 and α2δ-2 subunits of human voltage-gated calcium channels with high affinity and exhibits rapid dissociation from the α2δ-2 subunits.4 Given its pharmacological properties, mirogabalin appears to be a rational choice for PLMT, offering potential analgesic benefits for both central and peripheral neuropathic pain. However, the efficacy of mirogabalin for PLMT patients should be further validated through placebo-controlled clinical trials. Furthermore, the combination of other anti-Parkinson medications may offer benefits, given the analgesic effects that have been reported for clonazepam and levodopa in patients with neuropathic pain and Parkinson's disease.5, 6 However, the temporal relationship between initiation and pain relief suggests the efficacy of mirogabalin in the present case. A plausible pathophysiological mechanism for PLMT involves central nervous system remodelling induced by peripheral denervation. Regarding the association between pain and the central nervous system, impaired activation of nociceptive brain regions and lowered pain thresholds have been reported in patients with PD.7 PD is the second most common neurodegenerative disease characterized by central and peripheral nerve-derived synucleinopathy. Pain is a common non-motor symptom in patients with PD and significantly affects their quality of life.5 The aetiology of pain in PD is quite complex; however, the hypothesis that central pain processing impairments due to basal ganglia dopaminergic nerve degeneration, along with peripheral pain processing impairments due to molecular changes in the cytoskeleton and mitochondria in PD,5 align well with the central and peripheral theories of PLMT pathophysiology. Nevertheless, the lack of response to levodopa induction for pain does not fully support this hypothesis. Furthermore, not only striatal dopaminergic dysfunction, but also extrastriatal monoaminergic systems are thought to be involved in pain in patients with PD.7 It is suggested that the development of PLMT should be considered in the management of pain in PD patients. In addition, mild compression of the dural sac caused by lumbar canal stenosis at the L2/3 to L5/S1 levels may contribute to the development of PLMT. Past case series reported that two out of 10 patients with PLMT had canal stenosis, and one of them had mild sensory axonal neuropathy.2 Another case series reported that nearly 22% of cases among the patients with PLMT had radiculopathy, often at the L5 level.1 These reports suggest that canal stenosis could be a risk factor for developing PLMT. The presented case experienced pain mainly in the left toe, which is along the dermatome. However, canal stenosis and radiculopathy do not cause involuntary movements, which are a critical hallmark of diagnosing PLMT. These points are summarized in Fig. 4. We report the case of a patient with PLMT who was initially misdiagnosed as having a somatic symptom disorder. This case report provides three lessons: (i) PLMT is often misdiagnosed, and awareness of PLMT can help clinicians make accurate diagnoses; (ii) mirogabalin may be an option for PLMT; and (iii) the pathophysiology of PLMT is variable and requires individualized treatment. We acknowledge the patient and her family members. The authors declare that they have no conflicts of interest in the research. YM acquired case data and drafted the manuscript. KK and YY acquired case data. MS, SN, and MM supervised the study and substantively revised the manuscript. All authors read and approved the final manuscript. This case report was conducted in accordance with ethical guidelines for case reports of the Japanese Society of Psychiatry and Neurology. Written informed consent was obtained from the patient for publication of this report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Movie S1. The patient showed extension in the right toe and fine tremors in the left foot. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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