Introduction

Since the beginning of the Coronavirus disease 2019 (COVID-19) pandemic, an increasing number of functional neurological disorders (FND) have been reported in Covid-19 patients [1]. FND are characterized by common neurological symptoms such as movement disorders, paralysis, seizure, speech disorders and sensory impairment related to a functional, rather than a structural, disorder; symptoms are inconsistent and are incompatible with known neurological or medical conditions [2]. During the beginning of the COVID-19 pandemic, cases of functional movement disorders such as dystonia, gait disorders, tremor and non-epileptic seizure, more than doubled (9% versus 4% in previous years) in the Movement Disorders Unit of the Pitié-Salpêtrière University Hospital (Paris, France) [1]. Over 50% (10 out of 20) of patients admitted to the epilepsy monitoring unit in Texas hospital for urgent and emergent case evaluation during the first two months of pandemic presented psychogenic, non-epileptic seizures [3]. The prevalence of FND in the general population vary across studies, including approximately 12% of new neurology outpatient referrals in a large (3781 patients) prospective cohort study in the UK [4]. However, despite the global magnitude of Covid-19 pandemic and the high prevalence of neurological symptoms in patients with acute and long Covid-19, cases of FND have rarely been reported in this population [5,6,7,8]. The diagnosis of functional neurological symptoms may be specifically challenging in people with post Covid-19 condition, which is characterized by newly onset, fluctuating, or relapsing symptoms several months after initial recovery from Covid-19 [9].

Here we report 6 clinical cases of FND who were referred for rehabilitation of neurological symptoms of Covid-19 or complications of Covid-19 vaccine and discuss their common clinical traits, results of complementary neurological explorations and treatment/rehabilitation outcomes to facilitate their diagnostic and management.

Materials and methods

This case series included patients referred to the Institute Guttmann (Badalona, Barcelona, Spain) by a primary care physician or a specialist for evaluation of persistent symptoms and/or sequelae of COVID-19. All patients were evaluated by a Neurology or Physical Medicine and Rehabilitation specialist and a Neuropsychologist. When psychopathology was suspected, patients were also evaluated by a Psychiatrist. The diagnosis of functional neurological disorder was made according to the DSM-5 criteria [10]. Written informed consent for video publication was obtained from all patients.

A literature review was conducted in PubMed for articles on functional neurological disorders after Covid-19 infection or vaccination published from March 2020 to August 2022.

Case description

Sociodemographic characteristics, Covid-19 related clinical information, type of FND and results of complementary explorations are summarized in the Table 1.

Table 1 Sociodemographic characteristics and Covid-19 and FND related clinical information
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Case 1

A 50-year-old male business person, developed severe Covid-19 infection and required ICU admission, mechanical ventilation for 20 days, and treatment with Methylpredisolone, Lopinavir/Ritonavir and Hydroxychloroquine. He presented with lower limb weakness, hypoaesthesia and neuropathic pain due to right lumbosacral plexopathy as a sequelae of the prolonged prone position but was able to walk with a walker after 2 months of rehabilitation. At 11 months after the acute infection, the patient developed a new episode of progressive bilateral lower limb weakness. He was able to stand but unable to walk due to a sensation of having his feet glued to the ground. He required help for basic daily life activities and used an electric wheelchair to move around. He also complained of a burning sensation in his feet, sensation of full bladder without voiding desire, fatigue, and short-term memory alterations.

Neurological evaluation revealed bilateral lower limb weakness with inconsistent muscle strength at examination vs standing or transferring, trunk shaking and bilateral hand tremor at standing, distal symmetric hypoalgesia, and impaired vibration in the lower limbs (Video 1). Neuropsychological evaluation revealed mild attention impairment, memory retrieval difficulties and executive function impairment. The complementary exams revealed mild lesion of the left common peroneal nerve, incongruent with the severity of motor impairment. He underwent rehabilitation and was able to walk with a walker after 2 weeks of training.

Case 2

A 30-year-old female nursing assistant, 1 month after mild Covid-19 reported insidious onset, progressive right-sided muscle weakness, slowness of gait, loss of balance, impaired sensory perception with burning and pressure-type pain in the right hemibody, bradykinesia of the right hand, dysphagia and 2 isolated episodes of bladder and bowel incontinence. Due to neurological impairment, she became dependent on others for basic daily life activities and started using a crutch for walking. In addition, she reported symptoms of persistent cough, severe fatigue, and episodes of severe shortness of breath which led to multiple emergency room visits.

Her neurological examination revealed right-sided hemiparesis and generalized bradykinesia. The motor impairment was inconsistent and disappeared during distraction: the patient kept her arm close to the trunk while walking or sitting (as if it was glued to the body) but was able to extend and lean on the arm. In addition, the Barre test was negative; she was lifting her paralyzed leg with the left arm to get on and off the examination couch but no weakness was observed during neurological examination or walking (Video 2). She also presented right-side hypoalgesia with inconsistent midline boundaries on examination. The neuropsychological evaluation revealed impaired attention, memory, and executive functions, as well as symptoms of anxiety and depression. The complementary exams were normal. She was informed about the nature of FND and her motor symptoms spontaneously improved a few weeks later, being able to walk without crutches.

Case 3

A 43-year-old female pharmacist, developed progressive rubber leg and tingling sensation in the left leg, which led to loss of muscle strength and gait impairment two weeks after Covid-19 reinfection (15 months after the first episode) with mild symptoms. She had been using crutches and a wheelchair for about 2 weeks. She also complained of fatigue, memory problems and paraphasias. The neurological evaluation revealed inconsistent weakness of left foot dorsiflexion muscles with normal toe raising while standing and normal gait; marked slowness of movement; inconsistent left-side dysmetria with altered finger-to-nose and heel–knee–shin test, functional Romberg test with excessive trunk sway and falling passively backward or lateral with normal proprioceptive sensation (Video 3). The neuropsychological evaluation revealed mild attention impairment and symptoms of anxiety and depression. The complementary exams were normal. She underwent rehabilitation without changes.

Case 4

A 46-year-old female factory worker, presented with sudden bilateral lower limb weakness and a sensation of having the feet glued to the floor and knee buckling, which developed during the first week of mild Covid-19 infection. She needed support for standing and required assistance while walking to avoid falling. During the following weeks she developed head tremor and pelvis shaking, lower limb pain, and emotional lability. She was taking Sodium valproate and Clonazepam without reporting any effects. The neurological examination revealed intermittent head tremor with a varying pattern, which decreased or ceased with distraction maneuvers (for example while performing coordination tests) and at walk. During standing and walking, she presented with variable high amplitude flexion extension movements of the pelvis, waddling gait which persisted during tandem and backward walking, astasia–abasia without falling, dystonic movements with intermittent neck extension, scapular retraction and trunk rotation. She also presented severe bilateral lower limb weakness in supine position without any limb weakness with negative Mingazzini test (Video 4). The neuropsychological evaluation revealed mild attention and executive function and severe memory impairment with incongruous learning and recalling abilities, anxiety and depression. Her complementary exams were normal. She was recommended psychotherapy and a follow-up visit within 3 months.

Case 5

A 51-year-old male taxi driver, 4 days after mild Covid-19 infection, reported bilateral, sudden onset jerky movement of lower limbs in supine position during the early evening or later at night, which did not interfere with walking or driving. After 4 months, the episodes became less frequent but increased in amplitude, and he also noticed similar movements in the upper limbs. He has tried several drugs which were ineffective. His neurological examination was normal, and analysis of the home recorded videos revealed jerky movement of lower limbs with variable amplitude and frequency (Video 5). The neuropsychological evaluation revealed evocative mnesic impairment and significant anxious and depressive symptoms. The jerk-locked back averaging EEG revealed presence of Bereitschaftspotential prior to the movement onset. After his disability application was denied, the symptoms gradually improved and he was able to return to work.

Case 6

A 20-year-old female student, during the first week after her 2nd dose of Pfizer/BioNTech vaccine administration, reported exacerbated post Covid-19 fatigue. Over a 3 day period, she developed bilateral leg weakness, shaking legs and impaired gait: therefore, she started using a wheelchair to move around (Video 6). She also had paresthesia in the upper limbs. The neurological examination revealed normal motor balance in supine position with sudden knee buckling and shaking legs while walking or standing. The buckling disappeared during monopodal standing or dragging the feet. Her complementary exams were unremarkable. She was recommended psychotherapy but no further follow-up was scheduled in our center.

To summarize, the FND in our series were very heterogeneous and included motor impairment (hemiplegia, lower limb unilateral or bilateral paralysis), movement disorders (myoclonus, dystonia and tremor), and sensory and cognitive impairment (Table 1). Most patients were young female with mild Covid-19 infection who did not require hospital admission. One patient presented with overlapping symptoms of functional paraplegia and lesion of the left common peroneal nerve after prolonged ICU. Complementary neurological exams were useful to confirm the presence of a positive functional sign and to evaluate Covid-19 related residual neurological impairment (Table 1).

Discussion

The current case series characterizes clinical phenotypes, diagnosis and outcomes of FND in post Covid-19 patients. In our case series, most patients were young females (66.66%, mean age 34.75 years) presenting with clinically heterogeneous motor and sensory FND (movement disorders, limb weakness, numbness or pain and gait disorder), which is line with previous reports on FND after Covid-19 infection or vaccine administration (Table 2). However, whereas post Covid-19 functional symptoms usually developed during the first weeks of infection, FND after Covid-19 vaccine were commonly observed during the first 24 h after vaccine administration and included episodes of limb numbness and weakness mimicking polyneuropathies, functional seizure, short lasting twitches and transient nerve palsy.

Table 2 Review of the literature with case reports of FND after Covid-19 infection and vaccine
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Demographic and clinical phenotypes of FND in our population are in line with FND characteristics in a recent large meta-analysis including 4905 individuals (non Covid-19), which revealed a high prevalence of FND in women (72.6%) with a significantly earlier age of onset of FND in women (39.1 years) versus men (40.1 years) and mixed FND (23.1%), tremor (21.6%) and weakness (18.1%) as the most common phenotypes [11].

In our study, functional paralyses (lack of movement, weakness) were observed in four patients (#1, #2, #3, #4). These were characterized by fluctuating muscle strength with impaired voluntary movements but normal motor function during neurological examination or distraction maneuvers; dissociation between severe motor impairment in the lower limbs in sitting or supine position and preserved walking ability, similar to previous reports [12]. Other functional motor symptoms described in post Covid-19 patients, such as external rotation of the foot and leg-dragging gait pattern functional hemiplegia [8], drift without pronation in functional upper limb paresis [7] may support the functional nature of motor impairment.

Functional paroxysmal hyperkinetic movements, dystonia and gait disorders where the most common functional movement disorders that required urgent admission to a specialized unit during the COVID-19 pandemic [1]. Repetitive, irregular jerky leg movement observed in the patient #5 and other post Covid-19 patients [5, 6, 13] differ from myoclonic jerky movement produced by structural lesions: the former usually vary in amplitude and frequency, appear in supine position, and decrease with distraction, standing or walking [14]. In contrast, functional negative jerky movement in patient #6 was observed during walking and disappeared during monopodal standing or walking without lifting their feet off the ground and, despite severe gait impairment, the patient did not fall. The knee-buckling in these patients is slower compared to negative myoclonus seen in patients with hypoxic or metabolic encephalopathy [15]. Diagnosis of more complex movement disorders resembling choreodystonic movements, similar to those observed in patient #4, may be challenging. Gait disturbance characteristics such as excessive slowness of movements; walking on ice; sudden knee buckling; uneconomic postures; swaying from side to side without falling; astasia-abasia, and functional Romberg may be the key to their diagnosis [16].

In post Covid-19 patients, functional sensory and motor impairment are frequently associated, therefore mimicking stroke, spinal cord injury or polineuropathy [8, 13, 17, 18]. Fluctuating limb dysesthesia or sensory impairment with inconsistent midline boundaries on examination with exact splitting of sensation in the boundaries of specific dermatome or nerve territory observed in patient #1 are suggestive of FND. Numbness in the four extremities associated with pain or weakness resembling polyneuropathies, commonly beginning within 24 h of Covid-19 vaccine administration, were the most frequent phenotype of FND in a retrospective study in Japan [19]. Although uncommon, post-vaccination Guillain-Barré syndrome was reported as a major neurological complication of Covid-19 vaccine which generally appeared within 2 weeks of vaccine administration, as a result of molecular mimicry [20]. Therefore, nerve conduction studies, and CSF examination may be required for diagnostic purposes.

Although exhaustive instrumental examination is frequently conducted in patients with FND to exclude potential neurological damage, the results are usually normal or do not explain the neurological impairment. It is well known that over 20% of patients with FND may have and underlying neurological diseases [21, 22]. Therefore, instrumental diagnosis may be especially relevant in patients with suspected overlapping symptoms due to coexisting neurological diseases. In our study, complementary neurological explorations were normal in all patients, except for patient #1 who presented mild residual lesion of the left common peroneal nerve following prolonged ICU stay that did not explain his motor and gait impairment; therefore, pointing to overlapping symptoms of functional and structural neurological impairment. Other electrophysiological exams such as jerk-locked back averaging EEG with recording of Bereitschaftspotentials (indicating the involvement of the premotor cortex involvement in the preparation for movement) can be a useful diagnostic tools in patients with suspected functional myoclonus [23].

The diagnosis of non-motor FND in patients with long Covid-19 may be challenging. All patients in our study presented with other non-motor symptoms, such as fatigue, cognitive impairment and diffuse pain, which are common in post Covid-19 patients, regardless of the severity of acute infection [24]. However, their potential functional origin is not clear. The patient #4 reported severe memory impairment but the neuropsychological examination revealed incongruous learning and recalling abilities. Although “gold standard” diagnostic criteria for functional cognitive impairment are lacking, their functional nature is suggested by inconsistency between self-reported symptoms and objective cognitive deficits revealed by neuropsychological assessment [25].

Furthermore, four patients in our study presented with significant symptoms of anxiety or depression, which were exacerbated by or developed after acute Covid-19. FNDs are frequently comorbid with psychopathology such as anxiety, panic, depression, or posttraumatic stress disorders [2]. Although psychological comorbidity is not required for the diagnosis of FND, these are often triggered by stressful life events and physical injury [26]. During the Covid-19 pandemic, known patients with FND showed significantly higher levels of anxiety, perceived stress and symptoms related to post traumatic stress disorders compared to healthy controls [27]. Stressful life events related to infection and isolation by Covid-19, social media information suggesting neurological complications following Covid-19 infection may have contributed to appearance of FND. On the other hand, FND after vaccine may be triggered by psychological factors along with previous beliefs and expectations about vaccines. In 2021, in the context of videos circulating on social media which depicted individuals with continuous movements disorders and walking difficulties attributed to major neurologic adverse events after administration of the COVID-19 vaccine, with some of them diagnosed as FND, the US Centers for Disease Control and Prevention was warning that cases of FND may occur after administration of the COVID-19 vaccine but they are not the direct result of toxic vaccine effects and therefore do not mean the Covid-19 vaccines are unsafe. Rather, FND may be related to nocebo effects and negative expectations triggered by vaccine administration [28]. A systematic review by Amanzio et al. (2022) revealed that the adverse effects in the placebo group in patients enrolled in Covid-19 vaccine studies were more common in the younger population and in the first dose of placebo recipients of the mRNA vaccines, which accounted for over 70% of post vaccine symptoms, suggesting that negative expectation may play a major role in the occurrence of FND post vaccine [29].

Conclusions

There is a limited number of case reports of functional neurological disorders in post Covid-19 patients. The diagnostic of functional neurological symptoms in post Covid-19 patients may be specifically challenging in people with comorbid post Covid-19 condition and those with suspected non-motor functional symptoms. Is it important that clinicians recognize FND symptoms and to consider it as differential diagnosis in patients with neurologic complication of Covid-19 infection and vaccination.