key: cord-0893279-zn69nu5s authors: Vaz, Ana; Costa, Andreia; Pinto, André; Silva, Ana Isabel; Figueiredo, Paulo; Sarmento, António; Santos, Lurdes title: Complex Regional Pain Syndrome after severe COVID-19 – a case report. date: 2021-11-24 journal: Heliyon DOI: 10.1016/j.heliyon.2021.e08462 sha: 102afe694214a9d7232b484c7b945967ae0c5b28 doc_id: 893279 cord_uid: zn69nu5s Neurological complications are frequently reported in an intensive care unit (ICU), as a manifestation of a critical systemic illness or of its treatment. On the specific setting of COVID-19 patients, peripheral nerve lesions can have a multiplicity of causes, such as post-infectious neuropathy, positioning-related neuropathy or iatrogeny. An unusual but potentially disabling complication of any peripheral nerve lesion is Complex Regional Pain Syndrome (CRPS). Although there have been no mechanistic studies assessing how SARS-CoV-2 might directly impact nociception, it is hypothesized that the systemic hyperinflammation seen in severe COVID-19 may contribute to peripheral and central neuronal sensitization, possibly increasing the risk of developing CRPS. This case report highlights the potential hazards and consequences of peripheral nerve injuries on an ICU setting in COVID-19 patients, as well as the importance of a multidisciplinary approach for an early diagnosis and treatment, which are directly related to a better prognosis. Neurological complications are frequently reported in an intensive care unit (ICU), as a manifestation of a critical systemic illness or of its treatment 1 . These complications may present during the ICU stay (stroke, anoxic-ischemic injuries, peripheral nerve injuries, delirium, seizures) or after ICU discharge (Post-traumatic Stress Disorder and depression) 1 Peripheral nerve lesions usually follow a well-recognized clinical course, depending on lesions' topography and severity, but if there is a superimposed development of Complex Regional Pain Syndrome (CRPS), a diverse array of clinical features may develop 3, 4 . This syndrome is characterized by regional pain, seemingly disproportionate to the usual course of any known lesion, usually associated with a distal pattern of abnormal sensory, motor, sudomotor, vasomotor and/or trophic findings 3 . It may be clinically diagnosed through the Budapest Criteria and its severity could be accessed using the CRPS Severity Score (CSS) 3, 5 . The present therapeutic standard-of-care is a multimodality approach including patient education, rehabilitation, psychological support, and pharmacological intervention. 4 We report a case of 35-year-old woman, right-handed, previously independent in all basic and instrumental daily-life activities (DLA), with history of congenital confluent pink spots located on the dorsal surface of the hands and forearms, asthma and morbid obesity. The patient was admitted to an Infectious Twenty-four-hours later, the patient presented with a hematoma next to the line insertion site and absence of radial pulse. An upper-limb-doppler was requested, depicting a reduction of both radial and ulnar arteries flow. As so, the line was removed, and anticoagulation was started. A favorable clinical evolution was observed, and the patient was weaned from ventilation at the 12 th ICU Day. Ten days later, the neuro-motor examination revealed an asymmetric muscular strength On the clinical appointment three months after discharge, the patient presented with moderate pain of the left hand (Numeric Scale of Pain: 4/10), pinprick hyperesthesia on the dorsal surface of the hand, regional temperature and skin color asymmetry (with increased regional temperature and redness on the affected hand), trophic changes (absence of nails growth and altered skin texture -thickness), hand edema and a "pointing finger" deformity, maintaining the muscular strength impairment with predominant involvement of the distal left upper limb ( Figure 1A ). This complains impacted the performance of some DLA, namely driving, shopping and manual tasks requiring fine motor control (e.g. preparing food, management of financial matters and medication). Due to these clinical manifestations, and in accordance with Budapest Criteria, CRPS was diagnosed, with a severity score of 14 according to CSS (Table 1) . A multimodality therapeutic approach was started, including patient education, rehabilitation and pharmacologic intervention. The patient education was performed by a Neurologist and a Physical Medicine and Rehabilitation doctor, in accordance with the European Federation of Pain recommendations 4 . The rehabilitation approach included twice-a-week one-hour sessions of occupational therapy with the following techniques: contrast baths, joint mobilization of the hand and wrist, manual isometric muscular strengthening of intrinsic and extrinsic hand muscles, mirror visual feedback therapy, fine motor control reeducation and analgesic massage. The pharmacologic intervention consisted of a 2- week cycle of ibuprofen 400mg three-times a day. After eight weeks and fifteen rehabilitation sessions, there was a significative improvement on the patients' subjective complains and on objective measurements. Regarding subjective complains, the patient suffered paroxysmal pain less frequently, reported a subjective muscular strength increase that was confirmed on neuro-motor examination (scoring 4/5 on the MRC on the hand and wrist segments and 5/5 on the proximal segments of the left upper limb), maintaining the "pointing finger" deformity and an asymmetric vaso/sudomotor pattern. On objective measurements, the CSS was 7 points lower ( Figure 1B ), which represented as significant improvement in accordance with CSS smallest real difference value J o u r n a l P r e -p r o o f (4,9 points) . 5 Moreover, the patient was already able to perform all basic DLA and almost all instrumental DLA, including shopping, driving for small distances, managing financial matters and medication. Nonetheless, the patient still reported some disability on some steps of food preparation and heavy domestic work due to the lack of manual dexterity. Consequently, the therapeutic approach was further tailored, focusing specially on muscular strengthening and stretching, as well as on normalization of hand use and gesture reeducation, alongst with the prescription of ibuprofen on demand. Follow-up appointments were scheduled each 8-12 weeks to evaluate patients' evolution and optimize therapeutic interventions. Irrespective of the admission diagnosis, PNL are not rare in the ICU setting, and can occur after intravenous or intra-arterial line placement or removal. The most frequently affected nerves are the superficial branch of the radial nerve, the medial and lateral antebrachial cutaneous nerves and the radial and ulnar dorsal sensory branches of the hand 1 . PNL may result from pressure neuropraxia secondary to fluid extravasation or hematoma near the cannulation site, from chemical damage from medications or it can be directly inflicted by the needle 1 . CRPS is an unusual (incidence of 0.82/100000 person-years) but potentially disabling complication of any PNL, typically classified as type 2 in this context 4 . Given the heterogeneous and labile nature of the syndrome, clinical presentations may differ substantially between patients and even for the same patient time; therefore, assessment, tracking of changes and therapeutic planning may be challenging in the setting of CRPS. To our knowledge, this is the first report of CRPS after an iatrogenic nervous lesion on a critically ill COVID-19 patient. Although there have been no dedicated mechanistic studies at how the SARS-CoV- This case highlights a potential hazard of arterial puncture of the brachial artery -peripheral nervous lesions -, even under controlled conditions, specifically on COVID-19 patients. Although unusual, CRPS may occur after a peripheral nerve injury, leading to potentially significant function losses. An effective multidisciplinary approach is extremely important to attain a prompt diagnosis and successful treatment. We highlight the need of an increased awareness of this syndrome and its diagnostic and therapeutic approaches, both on acute and subacute stages after an injury 6 . This knowledge is critically important, because early diagnosis and treatment are associated with better prognosis 4,7 . J o u r n a l P r e -p r o o f Neurologic Complications in the Intensive Care Unit Neurobiology of SARS-CoV-2 interactions with the peripheral nervous system: implications for COVID-19 and pain Validation of proposed diagnostic criteria (the "Budapest Criteria") for Complex Regional Pain Syndrome Standards for the diagnosis and management of complex regional pain syndrome: Results of a European Pain Federation task force A prospective, multisite, international validation of the Complex Regional Pain Syndrome Severity Score Current practice in the rehabilitation of complex regional pain syndrome: a survey of practitioners day; 2 days Antivirals Oseltamivir, 75mg; 2/day; 5 days Non-steroidal anti-inflammatory drugs Ketorolac