Persistent postural perceptual dizziness (PPPD) in pediatric patients after COVID-19 infection

Abstract

Background:

Patients with long-COVID suffer from symptoms that continue or develop after a COVID-19 or SARS-CoV-2 infection and are present for four or more weeks after the initial infection. This case series describes a group of previously healthy adolescent patients with long-COVID who were seen in a pediatric vestibular clinic for evaluation of severe dizziness and were diagnosed with persistent postural-perceptual dizziness (PPPD). By presenting their symptoms, management and treatment effects, this study aims to provide a diagnostic and therapeutic framework for providers who encounter these patients.

Methods:

Patient records were reviewed for past medical history, symptoms, physical exam findings, results of audiometric and vestibular testing, dizziness handicap inventory for patient caregiver (DHI-pc) scores, and treatment recommendations. Parents of patients were contacted for a follow up survey to assess treatment adherence and outcomes including changes in symptoms and return to activity.

Results:

A series of 9 adolescent patients were referred from a multidisciplinary long-COVID clinic and diagnosed with PPPD. Recommended treatment included vestibular physical therapy, selective serotonin reuptake inhibitor medication, and cognitive behavioral therapy. The majority of patients experienced an improvement in their symptoms, and all patients had improved activity levels and DHI-pc scores after treatment.

Conclusion:

To the best of our knowledge, no previous reports exist discussing PPPD in long-COVID patients. This case series provides insight into symptom evolution and treatment efficacy in this patient population.

1. Introduction

The centers for disease control and prevention (CDC) defines long-COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC) as signs, symptoms, and conditions that continue or develop after initial COVID-19 or SARS-CoV-2 infection and are present for four or more weeks after the initial phase of infection. In adults, long-COVID is more common in patients who were hospitalized for an acute COVID-19 infection (54 % vs. 34 % in non-hospitalized adults), and their long-COVID symptoms typically include fatigue, muscle weakness, shortness of breath, sleep difficulties, anxiety and depression [1–3]. While less than 5 % of children with an acute COVID-19 infection require hospitalization, a recent systematic review found that the prevalence of long-COVID is 23.4 % in the pediatric population, with 6.2 % of these patients reporting dizziness [4,5]. Post-COVID dizziness has previously been attributed to Postural Orthostatic Tachycardia Syndrome (POTS), which, in children, is defined as an increase in heart rate of 40 beats per minute or more with standing up from a supine position and the absence of orthostatic hypotension in combination with symptoms such as light-headedness, palpitations, tremor, generalized weakness, blurred vision, and fatigue [6–9].

Persistent postural-perceptual dizziness (PPPD), which was previously known as chronic subjective dizziness, develops in adolescents and adults following a disorder or insult that causes dizziness, unsteadiness or vertigo, such as peripheral and central vestibular disorders, psychological distress or other medical illnesses. Patients with PPPD experience dizziness, unsteadiness, and/or non-spinning vertigo on most days for at least three months. Symptoms are typically exacerbated by upright posture, active or passive movement and exposure to moving or complex visual stimuli. Patients with PPPD experience significant distress and/or functional impairment [10]. The estimated overall prevalence of dizziness or imbalance in children is 5.6 % based on the 2016 National Health Interview [11]. Of pediatric patients with dizziness and/or imbalance seen at a large tertiary care center, 7.3–11.2 % were diagnosed with PPPD [12].

This case series describes a group of previously healthy adolescent patients with long-COVID who were seen in a pediatric vestibular clinic for evaluation of severe dizziness and were diagnosed with persistent postural-perceptual dizziness (PPPD). Given that dizziness worsens in upright posture with both POTS and PPPD, it is important for providers to be aware and screen for these conditions. This is the first report of PPPD developing in the setting of long-COVID infection. By presenting this cohort’s symptoms, treatments and treatment effects, this study aims to provide a diagnostic and therapeutic framework for providers who encounter these patients.

2. Methods

Approval for this study was obtained from the Institutional Review Board at Johns Hopkins University on November 6, 2023 (IRB00415301), and this study was conducted in compliance with the institutional guidelines. Informed consent was obtained from parents of pediatric patients and from patients over the age of 18 years at the time of survey.

A retrospective chart review was performed to identify long-COVID patients suffering from dizziness who were referred to the pediatric vestibular clinic of a tertiary care center and were diagnosed with PPPD. Patient charts were screened for age, past medical history, clinic visit dates, duration of symptoms, severity of symptoms based on the pediatric dizziness handicap inventory (DHI-pc) collected during the clinic visit, physical exam findings, audiometric findings, vestibular testing results, imaging and treatment recommendations [13].

Patients were initially evaluated in the long-COVID clinic at the Kennedy Krieger Institute (KKI) in Baltimore, MD, which provides multidisciplinary care to patients with persistent and new symptoms after an acute COVID-19 infection. During the initial clinical intake visit, patients were screened for symptoms of dizziness, lightheadedness, fatigue, headaches, and other orthostatic symptoms. Patients were also screened for any otologic complaints (e.g., tinnitus, hearing loss). Detailed patient history was obtained to further qualify clinical description of dizziness. A full neurological examination was conducted with vestibular testing when indicated based on history. If there was concern for orthostatic symptoms, patients underwent a passive standing test (PST) as part of their clinical evaluation to assess for POTS (description in Table 1) [9]. Patients with persistent dizziness that could not be attributed to POTS alone were referred to the multidisciplinary pediatric vestibular clinic at Johns Hopkins for further evaluation.

Table 1.

This table provides detailed descriptions of several diagnostic tests and criteria mentioned in the manuscript.

Test	Description
Passive standing test (PST)	This test was conducted in a quiet room and included BP and HR measurements using an automatic blood pressure cuff at 1 min intervals. Patients were placed in supine position for the first 5 min of the test after which they were instructed to stand with upper back leaning comfortably against a wall for 10 min with minimal stimulation, followed by return to the supine position for an additional 2 min. Patients were asked to verbally rate the severity of orthostatic symptoms on a scale of zero (no symptoms) to ten (maximum symptom severity) in 1-min intervals throughout the test, including fatigue, headaches, blurry vision, and dizziness.
POTS diagnosis based on PST [9]	HR increase by 40 bpm or more for ages 19 years and younger (or 30 bpm for ages 20 and 21) in the first 10 min of standing position compared to the supine position or had a standing HR greater than or equal to 120 bpm with increased orthostatic symptoms in the standing position and an absence of classic orthostatic hypotension
Word recognition scores	Presented at 40 dB SL scored as a percentage out of 25 words for each ear
Pure tone audiometry	Bone conduction thresholds were completed for 500–4000 Hz when indicated. Normal hearing was defined as audiometric thresholds <20 dB HL for all octave frequencies from 250 to 8k Hz that was symmetric (defined as <15 dB threshold difference between both ears at any tested frequency)
PPPD diagnostic criteria [10]	Presence of dizziness, unsteadiness, and/or non-spinning vertigo on most days for at least three months Symptoms are present without provocation, but can be exacerbated by upright posture, active or passive movement, and exposure to moving or complex visual stimuli Precipitating factors include disorders causing dizziness, unsteadiness and vertigo, such as peripheral and central vestibular disorders, psychological distress or other medical illnesses Symptoms cause significant distress or functional impairment, and 5. Symptoms are not better accounted for by another diagnosis
DHI-pc [13]	A questionnaire consisting of 21 questions regarding difficulties the patient is experiencing because of their dizziness with a total score ranging from 0 to 84. Based on this score the severity of participation and activity limitations are defined as follows: DHI-pc scores of 0–16, 17–26, 27–43 and > 43 are considered “no”, “mild”, “moderate” and “severe” participation and activity limitations respectively
Niigata PPPD questionnaire [14]	A 12 item questionnaire aiming to identify the difficulties in daily life activities that the patient may be experiencing due to dizziness. Patients were asked to rank each item on a scale from 0, meaning “no difficulty”, to 6, meaning this activity is “unbearable” resulting in a total score ranging from 0 to 72

Passive standing test: PST; Blood pressure: BP; Heart rate: HR; bpm: beats per minute; Decibel speech level: dB SL; Decibel hearing level: dB HL; Hertz: Hz; Persistent Postural Perceptual Dizziness: PPPD; DHI-pc: dizziness handicap inventory patient caregiver.

Evaluation in the multidisciplinary pediatric vestibular clinic included history and physical exam with a pediatric otolaryngologist, audiometric and vestibular testing, and physical therapy assessment. Physical examination at the pediatric vestibular clinic included evaluation of extra-ocular movements, primary gaze alignment, smooth pursuit, vergence, saccades, finger-to-nose and heel-to-shin coordination, gait, single leg stance, Romberg, Fukuda step testing, head impulse testing, nystagmus evaluation using Frenzel goggles (spontaneous, gaze evoked, nasal Valsalva, headshake and tragal compression) and positional testing for benign paroxysmal positional vertigo (BPPV). Physical therapy assessment included

Cervical movement screening to rule out cervicogenic dizziness and vertebrobasilar insufficiency, oculomotor assessment, motion sensitivity testing, balance assessments (including the modified clinical assessment of sensory interaction and balance), gaze stability assessments (including dynamic visual acuity testing) and positional testing for BPPV with treatment (Epley or Roll maneuver) if indicated.

Audiometric testing included pure tone audiometry, tympanometry, speech reception thresholds and word recognition scores (descriptions in Table 1). Vestibular testing included cervical and ocular vestibular myogenic potentials (cVEMP and oVEMP, respectively) testing which were rated as present versus absent, video head impulse testing (vHIT) which was rated as normal versus abnormal based on gain and refixation saccades, and video nystagmography (VNG), which was rated as normal versus abnormal.

In accordance with the consensus document of the committee for the Classification of Vestibular Disorders of the Bárány Society patients were diagnosed with PPPD if all 5 criteria were met (Table 1) [10].

Patients and parents were contacted for a follow up survey that included questions about treatment adherence and outcomes including change in symptoms and return to activity. Patients were asked if and how the following symptoms changed (remained stable, worsened or improved) as compared to their pediatric vestibular clinic visit: dizziness, poor balance, instability or unsteadiness, fatigue, headache, lightheadedness, brain fog, nausea, weakness, vision changes, anxiety, and depression. Patients were also asked to note if any other symptoms were present. In addition, patients were asked to specify the duration and frequency of their dizziness and/or whether this symptom was constantly present or episodic. They were also asked if any of the following factors provoked their dizziness: upright posture, motion, exercise or exertion, moving visual stimuli, complex patterns, loud sounds and light. Regarding treatment, patients were asked if they underwent vestibular physical therapy and/or cognitive behavioral therapy and for how many sessions and/or months, if they were taking any serotonin-reuptake inhibitors (SSRIs) and if so which medication and dosing they were using. They were also asked about the use of any other antidepressant or anti-anxiety medications. Patients were asked to rate their overall change in symptoms and activity level compared to their clinic visit as percentage worsening or improving. Regarding activity levels, the survey included questions about school and/or work attendance and whether patients were exercising and/or pursuing their hobbies and if so for how many days/hours per week. Patients were asked if they had any setbacks in their progress towards improvement of symptoms and activity levels and to describe these setbacks. The follow up survey included the dizziness handicap inventory for patient caregivers (DHI-pc) [13] and the Niigata PPPD questionnaire (see Table 1 for descriptions of questionnaires) [14].

A Wilcoxon signed rank test was performed to assess the change in DHI-pc scores after treatment. A Mann-Whitney U test was performed comparing the DHI-pc scores of long-COVID patients with PPPD to DHI-pc scores of non-PPPD patients seen in the same pediatric vestibular clinic. A p value of <0.05 was considered statistically significant. Statistical analysis was performed using SPSS (version 28.0; Chicago, IL).

3. Results

Between December 1st, 2021 and August 31st, 2023, a total of 91 patients were seen at the KKI long-COVID clinic. Dizziness was present in 83.5 % (76/91) of patients. Among those with dizziness, 24 patients underwent a standing test and were diagnosed with POTS. In addition, 12 patients were diagnosed with POTS prior to their initial evaluation at KKI. All 36 patients with POTS developed this disorder after their initial COVID-19 infection. 9 patients with severe persistent dizziness were diagnosed with PPPD after evaluation in the multidisciplinary pediatric vestibular clinic, 6 of whom also had POTS.

Of these 9 patients, 3 were male. Average age at time of evaluation was 15.1 years old (range: 10–20 years; Table 2). Past medical history included asthma and vocal cord dysfunction with exercise in one patient and Ehlers Danlos and irritable bowel syndrome in another. All other patients were previously healthy. All patients were previously asymptomatic; 8 patients developed symptoms after an acute COVID-19 infection, and 1 patient initially developed symptoms after a second COVID-19 vaccination, which worsened after an acute COVID-19 infection 6 months later.

Table 2.

Overview of patient sex, age at first clinic visit, dizziness type, duration of symptoms from start to first clinic visit, Dizziness Handicap Inventory for patient care givers (DHI-pc) at first clinic visit, abnormal physical exam findings and other diagnoses besides persistent postural perceptual dizziness (PPPD).

Patient number	Sex	Age at first clinic visit (years)	Dizziness type	Duration of symptoms from start to first clinic visit (months)	DHI-pc score at first clinic visit	Abnormal physical exam findingsa	Other diagnoses (in addition to PPPD)
1	M	10	Episodic	6	70	Gait, single leg stance, Romberg, and Fukuda step testing deferred due to standing intolerance	POTS
2	F	14	Episodic	11	46	Romberg (feet together) + sway but no falling. Right Dix-Hallpike with upbeating nystagmus	POTS, Vestibular migraine, BPPV
3	F	13	Constant	19	46	Single leg stance: Eyes closed 7–10 s	POTS (resolved), vestibular migraine
4	F	20	Episodic	16	24	Single leg stance: Eyes closed 2–5 s	POTS (resolved), vestibular migraine, seizures
5	M	16	Constant	16	52	Single leg stance: Eyes closed 7 s	POTS
6	F	17	Constant	34	62	Single leg stance: Eyes closed ~6 s	Vestibular migraine
7	M	13	Constant	9	44	Single leg stance: Eyes open 3–7 s, Eyes closed not attempted. Romberg not attempted. Head impulse testing: Right VOR - intermittent catch up saccades in all planes; Left VOR intermittent catch up saccades in all planes.	Vestibular migraine
8	F	17	Episodic	11	Not available	Single leg stance: Eyes closed 5 s	Vestibular migraine
9	F	16	Constant	22	66	Single leg stance: Eyes open ~5 s, Eyes closed 1–2 s. Romberg (feet together) sway but no fall. Frenzel: Left/right gaze-evoked: left-beating nystagmus in leftward gaze	POTS, vestibular migraine, vestibular hypofunction

^aSingle leg stance normal reference ≥5yo: ≥10 s.

Symptoms during the acute COVID-19 infection included fevers, congestion, sore throat, cough, shortness of breath, chest tightness, nausea, vomiting, muscle aches, headaches, lightheadedness, dizziness and tinnitus. No patients required hospitalization for their acute COVID-19 infection. The interval from start of vestibular symptoms to their first vestibular clinic visit ranged from 6 to 36 months (average: 16.4, 95%CI 13.7–19.2 months). All patients suffered from dizziness that could be provoked/worsened with triggering factors such as upright position, motion, exercise, moving visual stimuli, complex patterns, loud sounds and light and was present constantly in 5 patients while 4 patients suffered from episodic dizziness. In addition to their diagnosis of PPPD, 7 patients were diagnosed with vestibular migraine, 6 patients had POTS (2 of which had resolved by the time they were seen in the pediatric vestibular clinic), 1 had BPPV and 1 patient was diagnosed with seizures (Table 2).

Abnormal physical exam findings are included in Table 2. Abnormal single leg stance findings were seen in 7 patients, while 1 patient had normal findings and 1 patient could not participate due to symptoms (Table 2). On Romberg testing, 2 patients showed sway without falling, 5 had normal results, and 2 patients were unable to participate due to symptoms. Right-sided Dix-Hallpike was abnormal in 1 patient who had an immediate onset upbeating nystagmus, and this patient was subsequently treated with the Epley maneuver. Patient 9 had left-beating nystagmus on leftward gaze. All other physical exam findings were normal.

Abnormal physical therapy findings included abnormal dynamic visual acuity testing in 2 out of 9 patients (patient 3 and 5) and 1 patient (patient 6) had abnormal balance testing via the modified clinical assessment of sensory interaction and balance (mCTSB). All patients presented with abnormal motion sensitivity to head movements in the pitch, yaw, and diagonal planes for greater than 10 s.

Aside from one patient who had a unilateral 15 dB air-bone gap at two frequencies with normal tympanograms bilaterally, hearing was normal in all other patients. MRI brain had been obtained in all patients prior to clinic evaluation and was normal in all patients. Cervical vestibular evoked myogenic potential (cVEMP) and ocular vestibular evoked myogenic potential (oVEMP) responses were present in 8 patients, while 1 patient did not undergo VEMP testing. Video head impulse testing (vHIT) was performed in 7 patients, and one patient (patient 9) was noted to have a mildly reduced VOR in the left anterior canal. Of the 5 patients who underwent VNG testing, 1 had a left and up beating nystagmus post headshaking with a latent onset (patient 3), 1 had left caloric weakness (patient 5), while VNG was normal in the other 3 patients.

During their first pediatric vestibular clinic visit, 8 patients filled out the DHI-pc questionnaire and recorded an average score of 51.3 (range: 24–70; 95 % CI: 41.0–61.6; Fig. 1). For comparison, the average DHI-pc score among 32 patients seen in the pediatric vestibular clinic for dizziness and with diagnoses other than PPPD (including recurrent vertigo of childhood, vestibular migraine, benign paroxysmal positional vertigo, vestibular hypofunction, autonomic dysfunction, and post-concussive dizziness) was 31.8 (range 2–76; 95 % CI 25.1–38.5; Fig. 1), which is significantly lower (p = 0.008).

Fig. 1.

DHI-pc scores. DHI-pc scores are displayed on the Y-axis for three groups (X-axis): patients with PPPD plus long-COVID pre-treatment (closed circle), PPPD plus long-COVID post-treatment (open circle) and for patients seen in a pediatric vestibular clinic with diagnoses other than PPPD, including BPPV, vestibular hypofunction, recurrent vertigo of childhood and other diagnoses (closed square). The symbols represent average DHI-pc scores and the error bars indicate 95 % confidence intervals for the groups listed on the X-axis.

Recommended treatment for all PPPD patients included vestibular physical therapy (PT), cognitive behavioral therapy (CBT), and a selective serotonin reuptake inhibitor (SSRI).

Parents and/or patients were contacted to fill out the follow-up survey, and 8/9 agreed to participate. Follow-up time between the pediatric vestibular clinic visit to the survey ranged from 1 to 21 months (average: 8.8 months; Table 3). An overview of treatments and posttreatment effect for included patients is displayed in Table 3. All 8 patients underwent vestibular PT and attended an average of 27.4 (range: 11–60) sessions over an average of 4.9 (range: 1.5–8) months. 7/8 patients also underwent CBT with an average of 27 (range: 6–67) sessions and 5/8 took an SSRI (sertraline or fluoxetine) for an average of 7.8 (range: 1–13) months (Table 3). In addition, several patients with a concurrent vestibular migraine diagnosis had previously been on tricyclic antidepressants (TCA; patients 2, 3, and 8) without benefit and stopped this medication. All patients with vestibular migraine were on at least one abortive medication (Tylenol, non-steroidal anti-inflammatory drugs, and/or triptans), one patient was taking propranolol (patients 5) and one patient received botox injections (patient 9). Patients who had not yet tried a migraine diet or supplements such as magnesium, riboflavin, coenzyme Q and/or melatonin were recommended to do so.

Table 3.

Overview of treatments, estimated change in symptoms and activity level posttreatment, pre- and posttreatment DHI-pc scores and posttreatment Niigata PPPD score for patients who filled out the follow-up survey.

Patient #	Follow-up duration (months)	Vestibular PT (# of sessions)	Vestibular PT duration (months)	CBT (# of sessions)	CBT duration (months)	SSRI type	SSRI dose	SSRI duration (months)	Estimated improvement in symptoms at time of survey (%)	Estimated increase in activity level at time of survey (%)	DHI-pc score first clinic visit	DHI-pc score at time of survey	Niigata PPPD score at time of survey
1	6	60	4	40	6	Fluoxetine	10 mg daily	8	80	75	70	16	0
2	6	12	6	10	4	–	–	–	60	80	46	44	29
3	8	16	8	6	3	Sertraline	50 mg daily	6	0	35	46	44	35
4	21	20	1	15	1	–	–	–	95	95	24	20	3
5	13	20	8	24	12	Fluoxetine	20 mg daily	13	100	100	52	0	0
6	4	11	1.5	–	–	–	–	–	75	90	62	50	30
8	12	–	6	–	11	Sertraline	125 mg daily	11	99	99	–	–	1
9	1	53	5	67	21	Sertraline	100 mg daily	1	0	10	66	64	50

DHI-pc: dizziness handicap inventory patient caregiver; PT: physical therapy; CBT: cognitive behavioral therapy; SSRI: selective serotonin reuptake inhibitor.

The average estimated percentage improvement in overall symptoms was 63 % (range 0–100 %) and the average estimated percentage improvement in activity level was 73 % (range 10–100 %; Table 3). DHI-pc scores improved in all patients by 18 points on average (range: 2–54; p = 0.017; Table 3). The average post-treatment Niigata PPPD score was 18.5 (range: 0–50).

None of the patients experienced new symptoms at the time of the follow-up questionnaire. All but 2 patients (patient 5 and 8) continued to experience dizziness to some degree, although this symptom improved in 75 % of patients and remained stable in 25 % of patients (Fig. 2). From the 6 patients who continued to experience some degree of dizziness, triggering factors included exercise or exertion in all patients, moving visual stimuli and complex patterns in 5/6 patients, and motion, loud sounds and light in 4/6 patients. All but 2 patients experienced set-backs during the follow-up time, and these occurred after an illness or viral infection (n = 4), after a seizure (n = 1), after going back to school (n = 1) and after overdoing activity (n = 1).

Fig. 2.

Display of percentage of patients who reported a change (Y-axis) in symptoms listed on the X-axis. White bars represent patients who reported improvement in symptoms, black bars represent patients who reported worsening of symptoms, dark grey bars represent patients who reported stable symptoms, and light grey bars represent the proportion of patients who never experienced this symptom.

At the time of the follow-up questionnaire all patients were able to attend school 5 days a week ranging from 3 to 6.5 (average: 4.5) hours per day. All but 2 patients (patient 1 and 6) were able to exercise, and all but 1 patient (patient 9) were pursuing their hobbies.

4. Discussion

This report describes a group of pediatric patients who developed PPPD in the setting of long-COVID and were seen in a tertiary care pediatric vestibular clinic. While less common than in adults, PPPD has been identified in children [12,15]. PPPD is an underrecognized cause of chronic dizziness that results in a significant symptom burden, functional impact and days out of work and school. PPPD in children is also associated with functional gait disorders, migraines, and anxiety, all of which impact daily living and performance in school. To our knowledge no previous reports exist on PPPD in long-COVID patients. Although it remains to be determined if a relationship between the two pathologies exists, this case series provides insight into symptom evolution and treatment efficacy in this patient population. By raising awareness of this possible combination of diseases, this report aims to provide a framework for providers to ensure that patients receive proper treatment.

Meta-analyses assessing symptoms in pediatric long-COVID patients found a pooled prevalence of dizziness in 4.4–6.2 % of patients without further investigation of its cause other than long-COVID [5,16]. Multiple case series have reported on the development of POTS among pediatric and adult patients post-COVID, making this the most widely recognized secondary diagnosis contributing to dizziness in long-COVID patients [17–21]. A POTS prevalence of 30 % has been reported among adults with long-COVID, while the prevalence among pediatric patients is unknown [22]. Although dizziness in long-COVID patients can be a presenting symptom of POTS, further investigation is warranted especially in those patients who do not meet POTS criteria or who fail to improve with medical management. In this series, 6 patients had been diagnosed with POTS prior to evaluation but suffered from ongoing dizziness despite medical management of POTS.

Inner ear dysfunction has also been reported in the setting of COVID-19 infection. Colonization of the ear, middle ear and mastoid with SARS-CoV-2 has been demonstrated in patients with COVID-19 infections, which has been theorized to potentially lead to migration to the inner ear [23]. The development of SNHL after COVID-19 infection has been described in case series [24]. In addition, patients with post-COVID vertigo have been found to have high rates of abnormalities on video-nystagmography (VNG) testing suggestive of vestibular hypofunction [25]. The development of vestibular migraine has also been reported in a case report of two pediatric patients with long-COVID [26]. A concurrent vestibular migraine diagnosis is common in PPPD patients and found to occur in 56.6 % of pediatric PPPD patients [12]. Of the PPPD patients discussed in this report, 77.8 % had concurrent vestibular migraine (Table 2).

PPPD typically develops following a precipitating condition that causes vertigo, unsteadiness, or dizziness such as vestibular neuritis, BPPV, vestibular migraine and concussion [10]. COVID-19 infection with or without inner ear infection, long-COVID symptoms, and diagnoses including POTS and vestibular migraine that develop in the aftermath of COVID could all theoretically contribute to or lead to development of PPPD. Although the pathophysiology of PPPD is poorly understood, the combination of a triggering vestibular insult followed by insufficient compensation and psychological risk factors such as anxiety related personality traits have commonly been described in PPPD patients [27]. The areas of the brain that are important for compensation and coping seem to be affected in PPPD patients as evidenced by functional magnetic resonance imaging. Patients with PPPD were found to have reduced connectivity between areas involved in multisensory vestibular processing and spatial cognition, while increased connectivity was seen between visual and emotional processing networks [10,28]. Interestingly, reduction in serotonin has been proposed as a pathophysiologic mechanism for the development of long-COVID [29]. Although no studies exist assessing serotonin levels in PPPD patients, this population does seem to benefit from treatment with SSRIs [30].

Current treatments commonly prescribed for PPPD include pharmacologic (SSRIs and SNRIs) and non-pharmacologic (vestibular PT, CBT) treatments, and the patients described in this report were recommended to pursue all of these treatments [10,30–32]. After treatment, the majority of patients experienced improvements in symptoms and all had an increase in activity level (Table 3, Fig. 2). DHI-pc scores improved to a varying degree in all patients with 2 patients improving from “severe” (>43) to “mild” (0–16) participation and activity limitations, 1 patient remaining in the “mild” (17–26) category and 4 patients continuing have severe participation and activity limitations based on their DHI-pc scores of >43 [13]. For comparison, patients seen in the same pediatric vestibular clinic with non-PPPD diagnoses had significantly lower DHI-pc scores. Similar findings have been demonstrated in the adult PPPD population with adult PPPD patients having significantly higher DHI scores compared to non-PPPD dizzy patients [33]. Although to our knowledge differences in DHI-pc scores between PPPD and non-PPPD patients have not previously been investigated in the pediatric population, their symptom burden tends to be high as demonstrated by the high proportion of patients missing school or work [12]. Patients also reported overall improvements in symptoms (63 % on average) and activity level (73 % on average), the magnitudes of which were higher compared to the percentage improvement in DHI-pc score after treatment (35 % on average.

Limitations of this study include selection bias, as only patients with long-COVID requiring evaluation and treatment at a rehabilitation center with symptoms severe enough to prompt referral to an otolaryngologist were included in this study. Further studies are required to provide insight into the relationship between PPPD and long COVID in the pediatric population. In addition, there was heterogeneity of vestibular diagnoses in the patients included in this study. Although this is not uncommon in patients with PPPD, it does complicate treatment and assessment of treatment efficacy [34]. There is overlap in both symptoms and treatment of vestibular migraine and PPPD. Vestibular PT, CBT and serotonin-norepinephrine reuptake inhibitors (SNRI) have been proposed in both [35–38]. Other antidepressants used for vestibular migraine treatment include TCAs, while SSRIs have been recommended for treatment of PPPD [36,38]. In addition, several nonpharmacologic, abortive and preventative medications can be used for treatment of vestibular migraine that are not recommended in patients with PPPD [34,38]. The presence of persistent migraine symptoms could also limit the efficacy of PPPD treatments. Another limitation is that the DHI-pc questionnaire is not validated in adolescent patients. The DHI-pc score is validated in children ages 5–12 but is used, for practical purposes, for all patients upon intake in our pediatric vestibular clinic [13]. Similarly, the Niigata PPPD questionnaire was developed for adults but was used in this study as no alternative that has been validated in adolescents exists [14]. In addition, the self-reported percentages improvement in symptoms and activity level are not validated measures. This could possibly explain the discrepancy between average percentage improvement in symptoms (63 %) and activity level (73 %) and improvement in percentage DHI-pc score (35 %), although another possible explanation is that PPPD patients remain significantly affected by their remaining symptom burden. To the best of our knowledge, no placebo controlled randomized controlled trials (RCT) assessing the efficacy and harms of SSRIs or SNRIs, vestibular PT, or CBT have been performed in PPPD patients to date [39]. As this study was not an RCT, symptoms may have improved over time without intervention. To gain a better understanding of effective treatments for PPPD, RCTs assessing the different treatments are needed.

5. Conclusion

This case series is the first to describe development of PPPD after long-COVID. Plausible links between long-COVID and the development of PPPD were presented. The majority of patients experienced symptom and activity level improvements with treatments typically recommended for PPPD including vestibular PT, CBT and SSRI medication.