Management of Post-Stroke Cold Sensations: A Case Study on Sympathetic Nerve Ablation

Introduction

Stroke frequently results in a complex array of sequelae, including limb stiffness, spasms, and pain [1]. The pain can arise from various sources, such as central post-stroke pain, musculoskeletal pain, and neuropathic pain [2]. Joint or soft tissue pain is often caused by abnormal muscle tone, spasticity, or prolonged immobility due to paralysis, significantly impacting the lower limbs [3]. Additionally, spasticity in the muscles can lead to circulatory disorders in the affected limbs, contributing to cold-induced allodynia and pain [4]. Furthermore, post-stroke pain is common, with cold allodynia reported in 8% to 30% patients after stroke [5]. These symptoms are largely attributed to disruptions in peripheral circulation following a stroke. However, conventional treatments such as physical exercise, hyperbaric oxygen therapy, and pharmacological treatments have demonstrated limited efficacy in alleviating persistent limb coldness and associated symptoms caused by peripheral circulation disorders [6].

Computed tomography (CT)-guided sympathetic radiofrequency ablation has been proven to effectively regulate peripheral circulation, offering therapeutic benefits for conditions such as palmar and plantar hyperhidrosis, cold and clammy extremities, and Raynaud’s phenomenon [7,8]. Additionally, disturbances in peripheral circulation and cold sensations in the limbs have been linked to functional changes in specific brain regions, including the insular cortex, anterior cingulate cortex, thalamus, primary somatosensory cortex, and prefrontal cortex [9].

This report presents the case of a 65-year-old woman with post-stroke peripheral circulation disorders, characterized by reduced limb temperature and cold-induced pain. Following CT-guided sympathetic radiofrequency ablation, she experienced significant improvements in peripheral perfusion and limb temperature, as well as enhanced functional activity in temperature-related brain regions. This case highlights the potential of this approach as an effective therapeutic strategy for managing post-stroke circulatory disorders.

Case Report

A 65-year-old woman with a history of hypertension and over a year of cerebral infarction sequelae presented with abnormal cold sensation and increased muscle tension in her left upper and lower extremities. A decrease in ambient temperature triggered cold-associated pain in her limbs, leading to a visual analog scale pain score of 5. Consequently, she was admitted to the Pain Department of Jiaxing First Hospital.

Physical examination revealed decreased muscle strength on the patient’s left side, with grade 3 strength in the left upper limb and grade 4 in the left lower limb. The patient demonstrated increased muscle tone in both the upper and lower limbs, with an Ashworth score of 2, along with restricted shoulder joint mobility. The temperature of the left arm was 4°C lower than that of the healthy extremities. The patient was taking amlodipine 5 mg, atorvastatin 20 mg, and clopidogrel bisulfate 75 mg daily after experiencing stroke.

Magnetic resonance imaging (MRI) results indicated pontine malacia foci on the right side of the brain, interpreted as sequelae of a pontine infarction, along with bilateral periventricular ischemia (Figure 1A). CT angiography showed signs of arteriosclerosis in the lower extremity artery and reduced peripheral circulation in the left lower extremity (Figure 1B). Infrared thermography revealed that the temperature of the left leg was approximately 4°C lower than that of the right leg (Figure 1C). No significant abnormalities were observed in the blood routine or coagulation function tests. However, the patient had low high-density lipoprotein cholesterol level of 0.87 mmol/L and an elevated lipoprotein(a) level of 799.1 mg/L.

We used CT-guided radiofrequency ablation of the thoracic sympathetic nerve to treat post-stroke peripheral circulation disorders in the patient. All treatments were conducted with the patient’s informed consent and approval from the ethics committee. The patient was positioned prone on the CT table, and a scan was performed to identify the T3-4 vertebral space on the left side and the L3 vertebral body. We then designed an optimal puncture line targeting the gap between the left fourth rib head and the vertebral body (Figure 2A). Additionally, we located the lumbar sympathetic nerve at the level of the third lumbar vertebra using a scan with a 3-mm layer thickness. The calculated injection depth and angle allowed for precise targeting of the injection point, ensuring avoidance of the lungs, kidneys, small intestine, as well as surrounding nerves and blood vessels (Figure 2B). Following the designed trajectory, the needle was advanced through the T3-4 paravertebral space, crossing the costotransverse joint to reach the posterolateral edge of the T4 rib on the vertebral body (Figure 2C). As the needle approached the anterior aspect of the L3 vertebral body, it was carefully guided into the space between the abdominal aorta and the vertebral body under CT guidance (Figure 2D). After confirming the needle’s correct position via CT scan, we performed tests using a radiofrequency electrode to prevent unintended nerve damage. The resistance of the nerve tissue at the needle tip was maintained between 250 and 500 Ω. Electrical stimulation was applied at 0.8 mA, 0.3V, and 100 Hz, with no additional sensory responses observed. Further stimulation at 1 V and 2 Hz, and the absence of muscle twitches in the lower extremities and buttocks, confirmed that no motor responses were present, indicating that the needle tips were safely distanced from the spinal nerve. We then initiated standard radiofrequency therapy, setting the temperature to 75°C.

Thermocoagulation was maintained for 300 s, concluding the procedure. Throughout the operation, we continuously monitored vital signs, pulse oxygen saturation, peripheral perfusion index (PI), and palm temperature using a monitor.

As a result, our monitoring indicated a significant increase in the peripheral perfusion index (PI) in the patient’s left palm and feet immediately after surgery. The temperature of the left hand rose from 28°C to 33°C, while the temperature of the left foot increased from 27°C to 32°C. At 24 h after surgery, the temperature of the left limb continued to rise, surpassing that of the healthy side (Figure 3A). Additionally, the perfusion index increased from 0.7 to 3.4 in the palm and from 0.6 to 2.5 in the feet, further confirming the procedure’s success.

Further significant clinical improvement was observed during the follow-up visit 1 month after the sympathetic nerve radiofrequency ablation. The patient reported a subjective increase in warmth in the arms and legs, reduction in cold-induced pain, and visual analog scale score of 1.

Postoperative CT angiography showed improved collateral circulation, compared with that of the preoperative state (Figure 3B). Notably, an MRI performed 1 month after surgery revealed a significant reduction in pontine edema in the right side of the brain, indicating a positive change in the pontine malacia foci (Figure 3C).

In this case report, we used resting-state functional magnetic resonance imaging (rs-fMRI) to analyze changes in brain function after sympathetic nerve radiofrequency ablation surgery.

The amplitude of low-frequency fluctuations (ALFF) analysis method was used to calculate the blood oxygen level-dependent signal, reflecting the spontaneous activity level of each voxel in the brain. ALFF is a reliable and repeatable measure of brain functional activity under various physiological states [7].

The fMRI experimental procedure began with the acquisition of MRI sequences. T1-weighted sequences (repetition time=6.7 ms, echo time=2.9 ms, slice thickness=1 mm, number of slices=192, field of view=256×256 mm) were obtained and used as a structural reference for fMRI acquisition. The fMRI sequences were structured using a block paradigm, consisting of 36 volumes (number of slices=43, slice thickness=3.2 mm, repetition time=2000 ms, echo time=30 ms, field of view=220×220 mm, flip angle=90°, matrix size=64×64 mm).

We used SPM8 (https://www.fil.ion.ucl.ac.uk/spm/) and DPABI (http://rfmri.org/dpabi) for pre-processing, which included slice timing correction, realignment, motion correction, co-registration of T1 images to a human brain atlas, and spatial normalization of functional data. Images showing head movement exceeding 2 mm or 2° were excluded from the analysis. The images were then smoothed with a Gaussian kernel of 6×6×6 mm full-width at half-maximum to enhance the signal-to-noise ratio. The ALFF was extracted from the blood oxygen level-dependent signal images. We performed T-contrast analyses between pre-operation and post-operation phases, identifying regions with significant activation (P<0.005) and a cluster size exceeding 10 pixels.

In this patient, we observed heightened and reduced bilateral brain functional activation with statistical significance following sympathetic radiofrequency surgery, as illustrated in Figure 4. Specifically, we identified 5 regions of interest exhibiting increased neural activity 1 month after surgery: the left ventral anterior cingulate cortex, left angular gyrus, left cuneus, and right visual association cortex. Additionally, our analysis revealed decreased neural activation in 3 regions of interest: the anterior commissure, left parahippocampal region (LPH), and right parahippocampal region, as summarized in Table 1 and Figure 4. These brain regions can be associated with abnormal cold-induced pain sensation in patients with stroke. The observed brain function changes can help elucidate the underlying mechanisms of sympathetic radiofrequency surgery.

Discussion

The key takeaway from this case report is the presentation of post-stroke peripheral circulation disorders, characterized by increased spasticity, cold-induced pain, and a significant drop in temperature in the paralyzed limbs. This case underscores the importance of recognizing and addressing such complications and highlights the effectiveness of CT-guided sympathetic radiofrequency ablation. This intervention significantly improved the peripheral perfusion index, increased palm and foot temperature, and alleviated pain. These findings emphasize the need for proactive management of post-stroke sequelae, as this approach can significantly enhance patient outcomes.

Abnormal cold sensations in spastic limbs following a stroke are often overlooked, as patients and clinicians tend to prioritize the management of spasticity [10]. The diagnosis of post-stroke limb coldness primarily relies on subjective reports, with some patients also reporting cold-induced pain. However, these symptoms are far from rare, with studies indicating that approximately 53% of post-stroke patients experience an unpleasant cold sensation in the hemiplegic arm, significantly affecting their quality of life and causing considerable discomfort [11]. In the presented case, the cold sensation in the hemiplegic limb progressively intensified over time, with a marked worsening observed 6 months after stroke. Standard warming interventions, such as hot compresses, proved inadequate in relieving symptoms, and repeated attempts at medical treatment failed to provide effective solutions. The condition worsened further in winter, with exposure to cold air triggering cold-induced pain in the affected hand. This case underscores the critical need for heightened awareness and targeted therapeutic strategies to address these often-overlooked symptoms, thereby improving the quality of life and reducing the burden of post-stroke sequelae.

The causes of post-stroke limb coldness are multifactorial and involve a complex interplay of vascular, neurological, and muscle mechanisms. Reduced blood flow to the extremities, often influenced by vasomotor dysfunction, is a primary contributor to the cold sensation experienced by patients after stroke. This is further exacerbated by abnormal coagulation function and widespread vascular endothelial damage, which are common in patients after stroke and contribute to peripheral circulation disorders [12]. Additionally, irreversible neurological damage in the brain diminishes its inhibitory control over the sympathetic nervous system, leading to abnormal sympathetic excitation [13]. This heightened sympathetic activity increases vasoconstriction, reduces blood flow, and lowers skin temperature on the hemiplegic side [14]. Other contributing factors include sensory or perceptual disturbances caused by the stroke, reflex sympathetic dystrophy, and muscle disuse atrophy, all of which further intensify the cold sensations [15]. Understanding these mechanisms highlights the need for targeted interventions that address vascular and neurological dysfunctions, to improve outcomes in patients with post-stroke limb coldness.

Theoretically, sympathetic modulation could serve as a viable treatment option for post-stroke peripheral circulation disorders. There have been reports of using axillary sympathetic nerve blocks with ropivacaine to promote upper limb recovery in patients with frostbite [16]. Radiofrequency ablation of the sympathetic nerve is widely used in clinical practice for conditions such as hyperhidrosis, limb coldness, Raynaud syndrome, and lower extremity atherosclerosis obliterans [17]. Radiofrequency ablation has fewer severe complications than does chemical denervation with anhydrous ethanol [7] and offers significant benefits, including improved peripheral temperature regulation and relief of symptoms, such as dampness and coldness [18]. However, its potential application in managing post-stroke peripheral circulation disorders remains unexplored.

In this report, we used peripheral perfusion index mapping of the patient’s left palm and feet during surgery to evaluate the therapeutic effect in real time [19]. The perfusion index is a measure that assesses the adequacy of blood flow to the extremities by reflecting the ratio of pulsatile to non-pulsa-tile (static) blood flow at peripheral sites. A higher perfusion index indicates better peripheral perfusion and blood flow. Following radiofrequency ablation of the sympathetic nerve, the perfusion index increased from 0.7 to 3.4 in the palm and from 0.6 to 2.5 in the feet, confirming the success of the procedure. Additionally, the temperature of the left hand and foot gradually increased during surgery, and the symptoms were alleviated postoperatively. Subsequent infrared thermography and CT angiography confirmed that radiofrequency ablation of the sympathetic nerve improved collateral circulation and elevated limb temperatures. These findings demonstrate the potential of radiofrequency ablation as a treatment for post-stroke peripheral circulation disorders.

In this case report, we investigated the spontaneous neural activity in the brain using fMRI in a patient with post-stroke peripheral circulation disorders. Our findings demonstrated a significant increase in neural activity after radiofrequency ablation of the sympathetic nerve, particularly in the left ventral anterior cingulate cortex, left angular gyrus, left cuneus, and right visual association cortex, compared with preoperative levels. Notably, the ventral anterior cingulate cortex plays a critical role in thermal allodynia, hyperalgesia, and anxious behaviors in neuropathic pain models [20]. Improvements in visual function were also observed 1 month after surgery, as evidenced by increased intrinsic neural activity in the left angular gyrus and right visual association cortex. Moreover, distinct changes were detected in memory-related regions: the left cuneus, associated with working memory, exhibited heightened activity, while the bilateral para hippocampal regions showed reduced signals, indicating a shift towards spatial memory processing [21]. These alterations in brain activity suggest individualized responses, underscoring the importance of further research with larger sample sizes to identify specific brain regions that correlate with therapeutic efficacy in patients after stroke.

Conclusions

CT-guided radiofrequency ablation of the thoracic and lumbar sympathetic nerves effectively alleviates post-stroke peripheral circulation disorders, increases limb temperature, and improves collateral circulation. It also induces significant neural activity changes in brain regions associated with cold allodynia, highlighting its potential as an innovative therapeutic approach.