Paroxysmal sympathetic hyperactivity (PSH) is mainly reported in traumatic brain injury (TBI) cases. It includes striking clinical features of exacerbated sympathetic activity, including excessive sweating, tachycardia, arterial hypertension, tachypnoea, hyperthermia, decorticate or decerebrate posturing and increased muscle tone (Meyfroidt et al., 2017). PSH is often misdiagnosed as seizure, severe sepsis or bacteremia due to the lack of clinical experience (Godoy et al., 2019), especially as the first manifestation of some diseases. As a devastating stroke, acute large vessel occlusion (LVO) in the posterior circulation often leads to a very poor clinical prognosis. However, acute ischemic stroke is treatable if diagnosed early. To the best of our knowledge, there have been no reports describing PSH as the first manifestation of acute ischemic stroke. Here, we report three cases of acute LVO in the posterior circulation stroke with PSH as the first clinical manifestation and summarize the relevant literature in order to improve the understanding of this phenomenon, particularly emergency physicians.

The cases are summarized in Table 1. All patients were male, with a mean age of 63 (range, 61–65) years. Mean Glasgow Coma Scale (GCS) and PSH Assessment Measure (PSH-AM) scores were 4 and 19 (range, 18–20) (Baguley et al., 2014), respectively. All cases were successfully recanalized (TICI grade III) after mechanical thrombectomy, and the average time from symptom onset to recanalization was 358 min (range, 175–480). Two of the three patients died during the 90-day follow up period, and the mRS score of the survivor was 4.

PSH mainly occurs in TBI, accounting for about 80% of all cases; other causes include anoxic brain injury (10%), stroke (5%) and rare causes (5%) (Meyfroidt et al., 2017). The prevalence of ischemic stroke with PSH is lower than that of hemorrhagic stroke (a ratio of 1:4) (Perkes et al., 2010). There are no clinical randomized controlled trials assessing PSH in ischemic stroke. However, a few cases of ischemic stroke with PSH have been reported. Deepika et al. reported a 6-year-old girl with Moyamoya disease who developed PSH on the 3^rd day after indirect revascularization surgery (Deepika et al., 2014). In addition, Verma et al. described a 42-year-old male patient with acute right middle cerebral artery occlusion who developed PSH symptoms on the 10^th day of onset (Verma et al., 2015). Similarly, Siefferman et al. reported a 41-year-old male patient who developed PSH on the 8^th day after acute right middle cerebral artery ischemic stroke (Siefferman and Lai, 2015). Furthermore, Godoy et al. reported two young male patients with PSH symptoms after cerebral fat embolism (Godoy et al., 2018). Recently, Surathi et al. described a 64-year-old male patient who developed PSH symptoms 3 months after pontine infarction (Surathi et al., 2021). The patients reported in the above cases had better response to the treatment. Here, PSH as the first manifestation of acute LVO in the posterior circulation was reported in all three cases. To our knowledge, there is no related case report at present.

There was no unified diagnostic standard until the international consensus was reached in 2014 when the term of PSH was introduced (Baguley et al., 2014). The PSH-AM was designed to assess patients continuously from admission to intensive care unit (Baguley et al., 2014). The scale consists of two separate parts, including the clinical feature scale (CFS) and diagnosis likelihood tool (DLT) scores. The sum of CFS and DLT scores was used to evaluate the reliability of PSH diagnosis, with < 8 as unlikely, 8–16 as possible, and ≥17 as probable. All three patients we reported were assessed before treatment and the PSH-AM scores were >17, indicating probable diagnoses. However, in addition to rhythmic limb shaking, the clinical feature of paroxysmal limb shaking was not observed in these three patients. This may be explained by the following reasons: Firstly, different from TBI, acute ischemic stroke with PSH as the first manifestation can be treated by thrombolysis or mechanical thrombectomy. Secondly, the time from PSH symptom onset to the recovery of brain tissue reperfusion is too short to observe the frequency of PSH signs.

PSH occurs at any stage during the disorder that causes it (Godoy et al., 2019). However, it is usually observed in the first week after TBI. In the early stages of TBI, patients are often sedated to avoid secondary brain injury. This may mask the early classic features of PSH and delay diagnosis. Therefore, PSH as the first clinical manifestation is extremely rare, e.g., the three patients reported in this study. Previous studies have shown that chronic occlusion of the basilar artery caused by atherosclerosis often leads to small infarct lesions or transient ischemic symptoms. However, sudden embolism often causes extensive ischemic damage and poor clinical prognosis (Mattle et al., 2011). Notably, all the three current patients were complicated with atrial fibrillation. We speculate that embolism may be involved in the occurrence of PSH symptoms.

At present, which site of brain damage increases the odds of developing PSH remains unestablished. In 2015, Hinson et al. showed that disconnection between the posterior corpus callosum and the posterior limb of the internal capsule may promote the development of PSH (Hinson et al., 2015). LV et al. found that involvement of the corpus callosum, deep gray nuclei, periventricular white matter and midbrain/pons can increase the odds of developing PSH (Lv et al., 2010). Multiple infarct lesions were distributed in posterior circulation in our three patients. In case 1, cerebral infarction lesions were widely distributed in the posterior circulation, involving the corpus callosum, thalamus, temporal lobe, occipital lobe, cerebellum, midbrain and pons. Like case 1, case 2 also involved these structures, except the temporal lobe and corpus callosum, corroborating LV et al.'s study. Brain MRI showed that the lesion in case 3 involved the cerebellar hemisphere and PAG. We speculate that extensive disconnection due to multiple lesions in posterior circulation may play an important role in the occurrence and development of PSH. Coincidentally, a common feature of the three cases was that that the infarcted lesions involved the midbrain. A literature review showed that the PAG is presumed to play an important role in the central inhibitory driver, and structural or functional impairment of the midbrain may underlie the severer end of the PSH spectrum (Tang et al., 2009). This notion can also explain why the three patients still had a poor prognosis despite early endovascular treatment.

Currently, the evidence level of the best treatment strategy for PSH is low, being limited to case reports or case series. In practice, drug combinations with different mechanisms of action are used to control and prevent PSH symptoms. Meyfroidt et al. proposed three main treatment objectives for patients with PSH, including refraining from triggering factors, reducing excessive sympathetic outflow and nutritional support therapy (Meyfroidt et al., 2017). However, treatment of the primary disease causing PSH may play a crucial role. In the current three patients with acute LVO in the posterior circulation, PSH symptoms did not recur after the occluded vessels were recanalized by endovascular treatment.

PSH can be the initial symptom of acute LVO in the posterior circulation. Extensive disconnection due to multiple lesions in posterior circulation may promote the occurrence and development of PSH. Endovascular therapy may be effective for PSH signs caused by acute posterior circulation-related ischemic stroke. Further research is needed in the future for verification.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by the Ethics Committee of Xingtai Third Hospital (approval number: 2021-KY-28). The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

This study was supported by the Projects in Science and Technique Plans of Xingtai City [grant number 2021ZC108].

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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