1

The pain-free dimension of ALI and peripheral arterial embolism

• (i)
  

  In Haimovici’s review of 228 patients with 330 episodes of peripheral embolism, the source of emboli comprised rheumatic heart disease(40%), myocardial infarction(31.5%), arteriosclerotic heart disease(19.3%), infective endocarditis(4.3%), undetermined (3.1%).

Atrial fibrillation was prevalent in 81.5%.

Emboli were located in the femoral artery(38.5%), popliteal artery(14.2%), iliac artery(13.6%), aortic bifurcation(9.1%), and elsewhere.

The mode of symptom onset was carefully recorded in 240 cases. The onset was sudden in 195 cases, 143(59.5%)of whom had sudden pain, whereas as many as 52 patients(21.7%) had sudden numbness and coldness without initial pain. Instead of sudden onset of either numbness or coldness, 10 other patients had gradual onset of numbness and coldness.

In 17 cases the embolic event occurred apparently without any clinical manifestations except for the absence of peripheral pulses. In most of those cases “clinical examination prior to the embolic accidents had listed the presence of those pulses” [ ].

• (ii)
  

  In a review of his own series of 48 cases of peripheral arterial embolism, and in whom data regarding onset was adequate, Richards documented a sudden onset of symptoms in 37 cases. The initial symptom was most often pain, but numbness and coldness of the extremity, either sudden or progressive, preceded pain in about a third of cases” [ ].

  
  
• (iii)
  

  In more recent times, case series dated 2013 [ ], 2017 [ ], and 2020 [ ], respectively, also documented the pain-free dimension of ALI as follows:

In their six-year observational study of ALI in a local emergency department in Hong Kong, Yang et al. identified 78 patients with acute limb ischemia. Presenting symptoms were pain(63.1%), paresthesia(24.6%), pallor(18.5%), coldness(10.8%), paralysis(9.2%), gangrene(4.6%), pulselessness(1.5%). In other words, as many as 36.9% did not have pain as the initial symptom. Atrial fibrillation was an associated feature in 46.2% [ ].

In their retrospective observational study of 136 patients with ALI, Tripathy et al. identified a subgroup of 95 subjects with no evidence of prior atherosclerotic disease, and in whom clinical presentation occurred within 14 days of onset of symptoms. Sudden pain was the presenting feature in 76% [ ].

In their retrospective descriptive case study of 195 cases of ALI, Longenskiod et al. identified 117 patients who were ambulance transported and 78 who walked into hospital. The percentage of patients with rest pain amounted to 71% in the ambulance transported subgroup, and 52% in the walk-in subgroup [ ]. In other words, ALI patients who did not have pain as the initial symptom seemed to be unlikely to call an ambulance, thereby delaying timely clinical evaluation.

2

Specific locations and their pain-free component

Busuttil et al. reviewed their twenty-year experience of management of 26 cases of aortic saddle embolism. Motor and sensory deficits were the presenting feature in 92%. Rest pain was the presenting feature in 85% [ ].

3

Asymptomatic presentation of ALI in a recent case series

Among 81 patients with confirmed SARS-CoV-2 infection and concomitant arterial thrombotic complications there were 79 patients with ALI, and 2 patients with ALI and mesenteric thrombosis. Among those 81 patients there were 4 patients with asymptomatic presentation of arterial thrombosis [ ], presumably analogous with the 17 asymptomatic patients with peripheral arterial embolism documented by Haimovici [ ].

4

Anecdotal reports of pain free presentation of acute limb ischemia

• (i)
  

  A 67 year old woman presented with acute onset abdominal pain and vomiting but no limb pain. The underlying cause was superior mesenteric embolism attributable to atrial fibrillation. Treatment strategy comprised emergency enterectomy and anticoagulation with heparin. Postoperatively she gradually developed gangrene in her right hand. Computed tomography showed right brachial occlusion. Amputation was performed. At operation the arterial lumen was shown to be filled with organised embolus [ ].

  
  
• (ii)
  

  A 60 year old man presented with sudden loss of sensation and power in both legs. Computed tomography angiography showed acute thrombotic occlusion of the infrarenal aorta extending into the common iliac arteries. This was managed by thromboembolectomy. The underlying cause was hypercoagulability attributable to COVID-19 infection [ ].

5

Other aspects of acute limb ischemia

• (i)
  

  Paradoxical embolism(PDE) mediated by venous thromboembolism

One PDE scenario is characterised by the patient who presents with PDE-related acute limb ischemia in the presence of PE and/or deep vein thrombosis(DVT) [ ]. The occasional patient with PDE-related limb ischemia may, however, present with no symptoms of PE and no ultrasonographic evidence of DVT [ ]. In the latter example(Case 2) the patient developed symptoms of PE only on the third day following peripheral embolectomy [ ].

• (ii)
  

  Left atrial myxoma and other embolic sources in acute limb ischemia

In 1962 a literature review of 29 anecdotal reports of left atrial myxoma and 1 report of right atrial myxoma identified 9 cases of peripheral arterial embolism involving the iliac, femoral, and popliteal arteries [ ]. This diagnosis may be initially missed if echocardiography is not included in the workup of acute limb ischemia [ ].

Intracardiac hydatid cyst has also been reported as a source of embolic acute limb ischemia [ , ].

• (iii)
  

  Dissecting aortic aneurysm(DAA) presenting with acute limb ischemia

In this context, as with embolic acute limb ischemia, the clinical presentation can occur with pain [ ] or without pain [ , ].

A 67 year old man presented with acute onset right lower limb pain after using crack cocaine. The leg was cool to touch, and no pulses were palpable. Point of care ultrasound showed an intimal flap within the abdominal aorta. Computed tomography showed Stanford Type 2 DAA [ ].

In another report a 76 year old man only complained of sudden onset numbness and weakness of the left leg. The left dorsalis pulse was impalpable. Computed tomography showed aortic dissection extending from the aortic root to left external iliac artery [ ].

Sudden onset right hemiparesis, predominantly affecting the right leg, was the presenting feature in a 44 year old man with DAA. The right leg was cold. The femoral and the dorsalis pedis pulses were absent. Computed tomography angiography showed DAA involving the aortic root, with superior extension to all the aortic arch branches, and finally extending to the bifurcation of the abdominal aorta [ ].

In a MEDLINE literature review covering a period of 20 years, out of 1751 cases of DAA, 167(10%) were documented as having presented with acute leg ischemia [ ].

CRediT authorship contribution statement

Oscar M.P. Jolobe: Writing – review & editing, Writing – original draft, Visualization, Validation, Resources, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization.