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Clinical significance of spontaneous nystagmus in pediatric patients
International Journal of Pediatric Otorhinolaryngology 111 (2018) 103–107
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Clinical significance of spontaneous nystagmus in pediatric patients Guangwei Zhou a b
a,b,∗
a
a
, Cassandra Goutos , Sophie Lipson , Jacob Brodsky
T
a,b
Department of Otolaryngology and Communication Enhancement, Boston Children's Hospital, USA Department of Otolaryngology, Harvard Medical School, USA
A R T I C LE I N FO
A B S T R A C T
Keywords: Spontaneous nystagmus Peripheral vestibular disorders Central vestibular disorders Pediatric vestibular testing Videonystagmography Pediatric dizziness
Objective: To analyze spontaneous nystagmus recorded in pediatric patients and determine its diagnostic value. Materials and methods: Retrospective review of 86 patients (mean age = 13.9 ± 4.7 years) with definitive spontaneous nystagmus recorded by videonystagmography (VNG). Spontaneous nystagmus was categorized and analyzed based on its characteristics. Correlations between spontaneous nystagmus and established clinical diagnoses were explored. Results: Among the patients seen in a period of three years at our pediatric vestibular clinic, 15.4% (86 out of 560) were found to have spontaneous nystagmus and half of them had horizontal nystagmus with a fixeddirection. The majority of cases with spontaneous nystagmus (77%, 66/86) were present without fixation only, while the presence of spontaneous nystagmus with and without fixation was found in 16 patients (19%). Most patients with spontaneous nystagmus without fixation only (68%) were diagnosed with a peripheral vestibular disorder (e.g., vestibular neuritis) or vestibular migraine. In contrast, vertical nystagmus was found in 15 patients, most of whom had central vestibular disorders. Other rare forms of nystagmus or abnormal eye movements, such as pendular nystagmus, ocular oscillation or flutter were recorded in only four patients. Conclusions: Spontaneous nystagmus in children and young adults with possible vestibular impairments may vary in clinical presentation. Identification of its characteristics may help to make an accurate clinical diagnosis. While spontaneous nystagmus associated with peripheral vestibular disorders can be readily recognized, spontaneous nystagmus in pediatric patients with vestibular migraine appears to be more complex and variable in form.
1. Introduction It has been known for a long time that spontaneous nystagmus can be a key sign of vestibular dysfunction [1–7]. In a study published in 1982, authors were able to identify a lesion in 34 out of 41 adult patients for whom spontaneous nystagmus was the only abnormal finding [8]. Spontaneous nystagmus usually refers to involuntary rhythmic eye movements with alternating fast and slow components while the eyes are in the primary position (i.e., fixed in the midline/central gaze) without provoking stimuli [5,8]. Spontaneous nystagmus does not occur “spontaneously”, but rather is, most of the time, caused by an imbalance in the tonic vestibular inputs [9–12]. Not all spontaneous nystagmus can be seen easily with the naked eye during routine physical examination. In fact, Frenzel goggles are often used by specialists to identify suspected spontaneous nystagmus. The use of video goggles as in videonystagmography (VNG) makes the detection of spontaneous nystagmus even more definitive and quantifiable, which is extremely helpful in clinical evaluation of pediatric patients who may have
discreet or complex spontaneous nystagmus [13]. Many approaches have been used to describe spontaneous nystagmus. For example, spontaneous nystagmus can be designated as acquired or congenital based on the time of initial occurrence. To be valuable for clinical diagnosis, the characteristics of spontaneous nystagmus have to be recognized. An important feature of spontaneous nystagmus caused by peripheral vestibular pathology is that it is usually suppressed by visual fixation. If visual fixation fails to suppress spontaneous nystagmus, then a lesion in the central vestibular system should be considered [7,14–16]. The direction of the spontaneous nystagmus, typically named as the fast phase of nystagmus, also has clinical significance. While horizontal (left or right-beating) spontaneous nystagmus is usually seen in a peripheral vestibular loss, pure vertical (either up or down-beating) spontaneous nystagmus commonly denotes a lesion in the cerebellum or the brainstem [3,7,10,17–23]. Spontaneous nystagmus has been previously reported in children [24–29]. In our clinical practice, we have noted that spontaneous nystagmus seems to be more complicated and difficult to detect in
∗ Corresponding author. Balance and Vestibular Program, Department of Otolaryngology and Communication Enhancement, 9 Hope Ave., Boston Children's Hospital at Waltham, Waltham, MA, 02453, USA. E-mail address: [email protected] (G. Zhou).
https://doi.org/10.1016/j.ijporl.2018.06.007 Received 27 February 2018; Received in revised form 1 June 2018; Accepted 2 June 2018 Available online 05 June 2018 0165-5876/ © 2018 Elsevier B.V. All rights reserved.
International Journal of Pediatric Otorhinolaryngology 111 (2018) 103–107
G. Zhou et al.
pediatric patients for a variety of reasons. Although research studies on spontaneous nystagmus in adults have provided a good understanding of the pathogenesis of most cases, studies on the mechanism of spontaneous nystagmus in pediatric patients are limited [19,22,23,30–32]. To better understand the perplexing spontaneous nystagmus in children, we conducted a retrospective review of our pediatric patients with documented spontaneous nystagmus. 2. Methods We retrospectively reviewed our internal database of patients seen in the Balance and Vestibular Program at Boston Children's Hospital from July 2014 to June 2017. All patients with spontaneous nystagmus documented by VNG were identified. Following identification of these patients, the video files of spontaneous nystagmus, recorded using Micromedical VisualEyes system (Micromedical Technologies, Chatham, Illinois), were thoroughly reviewed. For the majority of patients, VNG was performed as a component of a vestibular test battery for dizziness, vertigo and/or balance problems. As a routine, these patients went through a comprehensive otologic and neurologic examination by a pediatric otolaryngologist who has a specialty in pediatric vestibular disorders. A small group of patients with known nystagmus were referred by pediatric ophthalmologists for VNG to better describe the nystagmus and/or rule out vestibular disorders. This retrospective study/chart review was approved by our hospital institutional review board. Electronic medical records of all included patients were also reviewed for demographics, clinical history, laboratory testing, imaging results, etc. Clinical diagnoses were verified and summarized. For patients with multiple diagnoses, their primary diagnosis was chosen for this analysis. Diagnoses of vestibular migraine and of benign paroxysmal vertigo of childhood were made based on the respective diagnostic criteria for these disorders outlined in the International Classification of Headache Disorders (ICHD), 3rd Edition [33]. Diagnosis of persistent postural perceptual dizziness (PPPD) was made based on the consensus criteria established by the Barany Society in 2016 [34]. Diagnosis of episodic ataxia, type 2 was confirmed by genetic testing demonstrating a mutation in the CACNA1A gene.
Fig. 1. Distribution of spontaneous nystagmus cases by fixation. The Y-axis represents the actual number of patients, and the percentages over the bars are out of the total 86 patients. Table 1 Spontaneous Nystagmus by Fixation and Associated Diagnoses (Total = 86 cases). Presence of Fixation
Primary Clinical Diagnosis
Number of Patients
Peripheral vestibular disorders Vestibular migraine Central vestibular/CNS disorders Cervical disorder Other known diagnoses Insignificant finding Inconclusive
25 20 9 2 3 2 5 Total = 66
Central vestibular/CNS disorders Congenital nystagmus Ocular motor dysfunction Associated with syndromic condition Inconclusive
7 5 2 1
Benign Paroxysmal Vertigo of Childhood Ocular motor dysfunction Episodic ataxia type 2 Vestibular neuritis + BPPV
1
Without only
With & Without
3. Results
1 Total = 16
With only
We found 560 patients who underwent VNG testing at our clinic from July 2014 to June 2017, and had video files available for review of spontaneous nystagmus. A total of 86 patients (15.4%) were identified with definitive spontaneous nystagmus. Among those with spontaneous nystagmus, 50 patients were female and 36 were male, with a mean age of 13.9 ( ± 4.7) years.
1 1 1 Total = 4
spontaneous nystagmus present without fixation at the time of this review. Out of 16 cases of spontaneous nystagmus present with and without fixation, seven cases were diagnosed with central vestibular and/or central nervous system disorders, such as cerebellar atrophy, seizure/ epilepsy. Five cases had the diagnosis of congenital nystagmus and two other cases had ocular motor dysfunction. There was 1 case that had a diagnosis of Muckle-Wells syndrome and one case without a conclusive diagnosis. Clinical diagnoses for four cases of spontaneous nystagmus present with fixation only were quite diverse, with details listed in Table 1.
3.1. Spontaneous nystagmus by fixation and associated diagnoses Overall, 77% (66/86) of patients had spontaneous nystagmus without visual fixation, as seen in Fig. 1. In contrast, spontaneous nystagmus present with fixation only was found in just four patients, less than 5% of all patients. Sixteen patients (about 19%) had spontaneous nystagmus with and without fixation. Regarding primary diagnosis, most of the patients (68%) who had spontaneous nystagmus present without fixation were diagnosed with peripheral vestibular disorders (25 cases) or vestibular migraine (20 cases), as outlined in Table 1. Peripheral vestibular disorders included vestibular neuritis, labyrinthitis, and benign paroxysmal positional vertigo (BPPV). Nine patients who had spontaneous nystagmus present without fixation were diagnosed with a central vestibular disorder or central nervous system (CNS) disorder. In two cases, we concluded that the spontaneous nystagmus was not clinically significant with consideration of their medical history and other examination and test findings. In addition, we could not make a definitive clinical diagnosis in five patients who had
3.2. Spontaneous nystagmus by direction and associated diagnoses To further characterize documented spontaneous nystagmus, we reorganized them by the direction of nystagmus: 1) Horizontal with a fixed direction, which included either left-beating or right-beating nystagmus; 2) Down-beating only; 3) Oblique or diagonal, in which 104
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G. Zhou et al.
Table 2 Spontaneous Nystagmus by Direction and Associated Diagnoses (Total = 86 cases). Present of Fixation
Primary Clinical Diagnosis
Horizontal Nystagmus-fixed direction Peripheral vestibular disorders Vestibular migraine Central vestibular/CNS disorders Congenital nystagmus Cervical cause Insignificant finding Inconclusive
Pure down-beating Nystagmus Central vestibular/CNS disorders Vestibular migraine Vestibular neuritis Cervical cause Inconclusive
Fig. 2. Distribution of spontaneous nystagmus cases by directionality. The Yaxis represents the actual number of patients, and the percentages over the bars are out of the total 86 patients.
spontaneous nystagmus moves diagonally (i.e., nystagmus with both horizontal and vertical components); 4) Torsional; 5) Up-beating only; 6) Horizontal with direction alternating; 7) Others, which included pendular nystagmus, ocular oscillations and ocular flutter. As shown in Fig. 2, the most commonly-seen spontaneous nystagmus was horizontal nystagmus with a fixed direction, and 50% (43/86) of all patients had this type of nystagmus. In about 23% (20/86) of all patients, spontaneous nystagmus direction was oblique/diagonal. In contrast, only two patients were found to have each of the following types of spontaneous nystagmus: torsional, pure up-beating and horizontal with alternating direction. Pendular nystagmus (1), ocular oscillations (2), or ocular flutter (1) were identified in the remaining four patients. For diagnoses, about 35% (15/43) of all patients with a fixed-direction horizontal nystagmus were eventually diagnosed with a peripheral vestibular disorder such as vestibular neuritis or labyrinthitis. In 38% (5/13) of all patients with pure down-beating nystagmus, diagnoses of central vestibular or central nervous system disorders were established. Detailed clinical diagnoses are summarized in Table 2. Most notably, spontaneous nystagmus in patients with a diagnosis of vestibular migraine had variable presentation, as shown in Fig. 3. Among all 86 patients in our study, the three most common categories of diagnoses were: vestibular migraine (24%), peripheral vestibular disorders (26%) and central vestibular disorders (29%), as shown in Fig. 4.
Oblique/Diagonal Nystagmus Central vestibular/CNS disorders Peripheral vestibular disorders Vestibular migraine Congenital nystagmus Ocular motor dysfunction PPPD
Pure up-beating Nystagmus Vestibular migraine Inconclusive
Horizontal Nystagmus- Direction alternating Central vestibular/CNS disorders Congenital nystagmus
Number of Patients
15 12 9 2 1 2 2 Total = 43
5 4 2 1 1 Total = 13
8 5 3 2 1 1 Total = 20
1 1 Total = 2
1 1 Total = 2
Torsional Central vestibular/CNS disorders Ocular motor dysfunction/palsy
Others (Ocular oscillations & flutters, Pendular nystagmus) Central vestibular/CNS disorders Vestibular migraine Inconclusive
1 1 Total = 2
1 1 2 Total = 4
4. Discussion With the aid of VNG, we were able to document spontaneous nystagmus in a relatively large group of pediatric patients. Although the overall percentage of our patients identified with spontaneous nystagmus is not particularly high, around 15%, we feel that the detection and characterization of the spontaneous nystagmus was very helpful in establishing a clinical diagnosis. We first looked at the effect of visual fixation on spontaneous nystagmus for interpretation, following an established routine [5]. Similar to published studies, we noticed spontaneous nystagmus that can be suppressed by visual fixation presented more often in peripheral vestibular disorders, such as vestibular neuritis and labyrinthitis, while non-suppressible spontaneous nystagmus presented more often in central disorders [1,3,14,16,24,26,35]. We did observe that fixation suppression of spontaneous nystagmus varied among patients with a diagnosis of vestibular migraine. Although vestibular migraine has generally been thought to occur primarily within the brain itself [36–38], numerous studies have also shown evidence of variable degrees of peripheral vestibular dysfunction in adult patients with vestibular migraine [39–44]. Such peripheral vestibular impairment has been theorized to occur in vestibular migraine patients via
Fig. 3. Variable spontaneous nystagmus in patients with vestibular migraine. The Y-axis represents the actual number of patients, and the percentages over the bars are out of the total 21 patients with vestibular migraine.
direct effects of the trigemino-vascular pathway on the peripheral vestibular organs [45–48]. Our findings further support this increasingly popular theory that vestibular migraine may have effects on both 105
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Fig. 4. Distribution of diagnoses of common vestibular disorders (vestibular migraine, peripheral & central vestibular disorders) in all 86 patients.
nystagmus, a discussion with an ophthalmologist may be beneficial.
the brain and the inner ear. Our next focus on spontaneous nystagmus was regarding direction. Different from previous reports of spontaneous nystagmus in children being only horizontal [27], the complexity of direction of spontaneous nystagmus in children is evident in our study. As expected, fixed-direction horizontal spontaneous nystagmus was the most common (50% of the total patients). This type of spontaneous nystagmus may be present in many patients with peripheral vestibular disorders. Nonetheless, we only found about 35% (15 out of 43) of patients were diagnosed with peripheral vestibular disorders in our study. Therefore, other diagnoses such as central vestibular disorders or vestibular migraine can't be ruled out in this situation. Oblique/diagonal spontaneous nystagmus was the second most frequently documented, in about 23% of patients, and these patients had quite diverse diagnoses. Pure down-beating spontaneous nystagmus is commonly associated with brainstem and cerebellar lesions [21–23]. About 15% of our patients had this type of spontaneous nystagmus, and some of these patients were found to have a cerebellar lesion such as a Chiari I malformation, but others were diagnosed with vestibular migraine, again supporting the potentially diffuse impacts of vestibular migraine. The diagnostic value of spontaneous nystagmus has been controversial since spontaneous nystagmus was reportedly seen in some normal subjects [1,49,50]. However, in our study, we found spontaneous nystagmus recorded by VNG in pediatric patients with vestibular complaints or symptoms to be a pathologic finding in nearly all cases, with the exception of just two cases. While the presence of spontaneous nystagmus alone can't be used to make a diagnosis of vestibular disorder, we have found the presence and characteristics of spontaneous nystagmus to be a valuable complement to a comprehensive history and examination and other vestibular testing results in determining the cause of pediatric patients vestibular symptoms. For example, 50% of our patients with spontaneous nystagmus were eventually diagnosed with either vestibular migraine or peripheral vestibular disorders. Limitations of our study include the retrospective format and lack of a normal subject group for comparison. Although we chose the primary diagnosis in our analysis, some patients had more than one clinical diagnosis, which may complicate presenting nystagmus. Even with our best efforts and all available exam outcomes, we could not make a definitive diagnosis in 6 cases, which we called inconclusive. Interpretation and diagnosis of rarely-seen spontaneous nystagmus such as torsional and direction-alternating nystagmus warrant extra caution. In cases with ocular oscillations and flutters that mimic spontaneous
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Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Clinical significance of spontaneous nystagmus in pediatric patients Guangwei Zhou a b
a,b,∗
a
a
, Cassandra Goutos , Sophie Lipson , Jacob Brodsky
T
a,b
Department of Otolaryngology and Communication Enhancement, Boston Children's Hospital, USA Department of Otolaryngology, Harvard Medical School, USA
A R T I C LE I N FO
A B S T R A C T
Keywords: Spontaneous nystagmus Peripheral vestibular disorders Central vestibular disorders Pediatric vestibular testing Videonystagmography Pediatric dizziness
Objective: To analyze spontaneous nystagmus recorded in pediatric patients and determine its diagnostic value. Materials and methods: Retrospective review of 86 patients (mean age = 13.9 ± 4.7 years) with definitive spontaneous nystagmus recorded by videonystagmography (VNG). Spontaneous nystagmus was categorized and analyzed based on its characteristics. Correlations between spontaneous nystagmus and established clinical diagnoses were explored. Results: Among the patients seen in a period of three years at our pediatric vestibular clinic, 15.4% (86 out of 560) were found to have spontaneous nystagmus and half of them had horizontal nystagmus with a fixeddirection. The majority of cases with spontaneous nystagmus (77%, 66/86) were present without fixation only, while the presence of spontaneous nystagmus with and without fixation was found in 16 patients (19%). Most patients with spontaneous nystagmus without fixation only (68%) were diagnosed with a peripheral vestibular disorder (e.g., vestibular neuritis) or vestibular migraine. In contrast, vertical nystagmus was found in 15 patients, most of whom had central vestibular disorders. Other rare forms of nystagmus or abnormal eye movements, such as pendular nystagmus, ocular oscillation or flutter were recorded in only four patients. Conclusions: Spontaneous nystagmus in children and young adults with possible vestibular impairments may vary in clinical presentation. Identification of its characteristics may help to make an accurate clinical diagnosis. While spontaneous nystagmus associated with peripheral vestibular disorders can be readily recognized, spontaneous nystagmus in pediatric patients with vestibular migraine appears to be more complex and variable in form.
1. Introduction It has been known for a long time that spontaneous nystagmus can be a key sign of vestibular dysfunction [1–7]. In a study published in 1982, authors were able to identify a lesion in 34 out of 41 adult patients for whom spontaneous nystagmus was the only abnormal finding [8]. Spontaneous nystagmus usually refers to involuntary rhythmic eye movements with alternating fast and slow components while the eyes are in the primary position (i.e., fixed in the midline/central gaze) without provoking stimuli [5,8]. Spontaneous nystagmus does not occur “spontaneously”, but rather is, most of the time, caused by an imbalance in the tonic vestibular inputs [9–12]. Not all spontaneous nystagmus can be seen easily with the naked eye during routine physical examination. In fact, Frenzel goggles are often used by specialists to identify suspected spontaneous nystagmus. The use of video goggles as in videonystagmography (VNG) makes the detection of spontaneous nystagmus even more definitive and quantifiable, which is extremely helpful in clinical evaluation of pediatric patients who may have
discreet or complex spontaneous nystagmus [13]. Many approaches have been used to describe spontaneous nystagmus. For example, spontaneous nystagmus can be designated as acquired or congenital based on the time of initial occurrence. To be valuable for clinical diagnosis, the characteristics of spontaneous nystagmus have to be recognized. An important feature of spontaneous nystagmus caused by peripheral vestibular pathology is that it is usually suppressed by visual fixation. If visual fixation fails to suppress spontaneous nystagmus, then a lesion in the central vestibular system should be considered [7,14–16]. The direction of the spontaneous nystagmus, typically named as the fast phase of nystagmus, also has clinical significance. While horizontal (left or right-beating) spontaneous nystagmus is usually seen in a peripheral vestibular loss, pure vertical (either up or down-beating) spontaneous nystagmus commonly denotes a lesion in the cerebellum or the brainstem [3,7,10,17–23]. Spontaneous nystagmus has been previously reported in children [24–29]. In our clinical practice, we have noted that spontaneous nystagmus seems to be more complicated and difficult to detect in
∗ Corresponding author. Balance and Vestibular Program, Department of Otolaryngology and Communication Enhancement, 9 Hope Ave., Boston Children's Hospital at Waltham, Waltham, MA, 02453, USA. E-mail address: [email protected] (G. Zhou).
https://doi.org/10.1016/j.ijporl.2018.06.007 Received 27 February 2018; Received in revised form 1 June 2018; Accepted 2 June 2018 Available online 05 June 2018 0165-5876/ © 2018 Elsevier B.V. All rights reserved.
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pediatric patients for a variety of reasons. Although research studies on spontaneous nystagmus in adults have provided a good understanding of the pathogenesis of most cases, studies on the mechanism of spontaneous nystagmus in pediatric patients are limited [19,22,23,30–32]. To better understand the perplexing spontaneous nystagmus in children, we conducted a retrospective review of our pediatric patients with documented spontaneous nystagmus. 2. Methods We retrospectively reviewed our internal database of patients seen in the Balance and Vestibular Program at Boston Children's Hospital from July 2014 to June 2017. All patients with spontaneous nystagmus documented by VNG were identified. Following identification of these patients, the video files of spontaneous nystagmus, recorded using Micromedical VisualEyes system (Micromedical Technologies, Chatham, Illinois), were thoroughly reviewed. For the majority of patients, VNG was performed as a component of a vestibular test battery for dizziness, vertigo and/or balance problems. As a routine, these patients went through a comprehensive otologic and neurologic examination by a pediatric otolaryngologist who has a specialty in pediatric vestibular disorders. A small group of patients with known nystagmus were referred by pediatric ophthalmologists for VNG to better describe the nystagmus and/or rule out vestibular disorders. This retrospective study/chart review was approved by our hospital institutional review board. Electronic medical records of all included patients were also reviewed for demographics, clinical history, laboratory testing, imaging results, etc. Clinical diagnoses were verified and summarized. For patients with multiple diagnoses, their primary diagnosis was chosen for this analysis. Diagnoses of vestibular migraine and of benign paroxysmal vertigo of childhood were made based on the respective diagnostic criteria for these disorders outlined in the International Classification of Headache Disorders (ICHD), 3rd Edition [33]. Diagnosis of persistent postural perceptual dizziness (PPPD) was made based on the consensus criteria established by the Barany Society in 2016 [34]. Diagnosis of episodic ataxia, type 2 was confirmed by genetic testing demonstrating a mutation in the CACNA1A gene.
Fig. 1. Distribution of spontaneous nystagmus cases by fixation. The Y-axis represents the actual number of patients, and the percentages over the bars are out of the total 86 patients. Table 1 Spontaneous Nystagmus by Fixation and Associated Diagnoses (Total = 86 cases). Presence of Fixation
Primary Clinical Diagnosis
Number of Patients
Peripheral vestibular disorders Vestibular migraine Central vestibular/CNS disorders Cervical disorder Other known diagnoses Insignificant finding Inconclusive
25 20 9 2 3 2 5 Total = 66
Central vestibular/CNS disorders Congenital nystagmus Ocular motor dysfunction Associated with syndromic condition Inconclusive
7 5 2 1
Benign Paroxysmal Vertigo of Childhood Ocular motor dysfunction Episodic ataxia type 2 Vestibular neuritis + BPPV
1
Without only
With & Without
3. Results
1 Total = 16
With only
We found 560 patients who underwent VNG testing at our clinic from July 2014 to June 2017, and had video files available for review of spontaneous nystagmus. A total of 86 patients (15.4%) were identified with definitive spontaneous nystagmus. Among those with spontaneous nystagmus, 50 patients were female and 36 were male, with a mean age of 13.9 ( ± 4.7) years.
1 1 1 Total = 4
spontaneous nystagmus present without fixation at the time of this review. Out of 16 cases of spontaneous nystagmus present with and without fixation, seven cases were diagnosed with central vestibular and/or central nervous system disorders, such as cerebellar atrophy, seizure/ epilepsy. Five cases had the diagnosis of congenital nystagmus and two other cases had ocular motor dysfunction. There was 1 case that had a diagnosis of Muckle-Wells syndrome and one case without a conclusive diagnosis. Clinical diagnoses for four cases of spontaneous nystagmus present with fixation only were quite diverse, with details listed in Table 1.
3.1. Spontaneous nystagmus by fixation and associated diagnoses Overall, 77% (66/86) of patients had spontaneous nystagmus without visual fixation, as seen in Fig. 1. In contrast, spontaneous nystagmus present with fixation only was found in just four patients, less than 5% of all patients. Sixteen patients (about 19%) had spontaneous nystagmus with and without fixation. Regarding primary diagnosis, most of the patients (68%) who had spontaneous nystagmus present without fixation were diagnosed with peripheral vestibular disorders (25 cases) or vestibular migraine (20 cases), as outlined in Table 1. Peripheral vestibular disorders included vestibular neuritis, labyrinthitis, and benign paroxysmal positional vertigo (BPPV). Nine patients who had spontaneous nystagmus present without fixation were diagnosed with a central vestibular disorder or central nervous system (CNS) disorder. In two cases, we concluded that the spontaneous nystagmus was not clinically significant with consideration of their medical history and other examination and test findings. In addition, we could not make a definitive clinical diagnosis in five patients who had
3.2. Spontaneous nystagmus by direction and associated diagnoses To further characterize documented spontaneous nystagmus, we reorganized them by the direction of nystagmus: 1) Horizontal with a fixed direction, which included either left-beating or right-beating nystagmus; 2) Down-beating only; 3) Oblique or diagonal, in which 104
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Table 2 Spontaneous Nystagmus by Direction and Associated Diagnoses (Total = 86 cases). Present of Fixation
Primary Clinical Diagnosis
Horizontal Nystagmus-fixed direction Peripheral vestibular disorders Vestibular migraine Central vestibular/CNS disorders Congenital nystagmus Cervical cause Insignificant finding Inconclusive
Pure down-beating Nystagmus Central vestibular/CNS disorders Vestibular migraine Vestibular neuritis Cervical cause Inconclusive
Fig. 2. Distribution of spontaneous nystagmus cases by directionality. The Yaxis represents the actual number of patients, and the percentages over the bars are out of the total 86 patients.
spontaneous nystagmus moves diagonally (i.e., nystagmus with both horizontal and vertical components); 4) Torsional; 5) Up-beating only; 6) Horizontal with direction alternating; 7) Others, which included pendular nystagmus, ocular oscillations and ocular flutter. As shown in Fig. 2, the most commonly-seen spontaneous nystagmus was horizontal nystagmus with a fixed direction, and 50% (43/86) of all patients had this type of nystagmus. In about 23% (20/86) of all patients, spontaneous nystagmus direction was oblique/diagonal. In contrast, only two patients were found to have each of the following types of spontaneous nystagmus: torsional, pure up-beating and horizontal with alternating direction. Pendular nystagmus (1), ocular oscillations (2), or ocular flutter (1) were identified in the remaining four patients. For diagnoses, about 35% (15/43) of all patients with a fixed-direction horizontal nystagmus were eventually diagnosed with a peripheral vestibular disorder such as vestibular neuritis or labyrinthitis. In 38% (5/13) of all patients with pure down-beating nystagmus, diagnoses of central vestibular or central nervous system disorders were established. Detailed clinical diagnoses are summarized in Table 2. Most notably, spontaneous nystagmus in patients with a diagnosis of vestibular migraine had variable presentation, as shown in Fig. 3. Among all 86 patients in our study, the three most common categories of diagnoses were: vestibular migraine (24%), peripheral vestibular disorders (26%) and central vestibular disorders (29%), as shown in Fig. 4.
Oblique/Diagonal Nystagmus Central vestibular/CNS disorders Peripheral vestibular disorders Vestibular migraine Congenital nystagmus Ocular motor dysfunction PPPD
Pure up-beating Nystagmus Vestibular migraine Inconclusive
Horizontal Nystagmus- Direction alternating Central vestibular/CNS disorders Congenital nystagmus
Number of Patients
15 12 9 2 1 2 2 Total = 43
5 4 2 1 1 Total = 13
8 5 3 2 1 1 Total = 20
1 1 Total = 2
1 1 Total = 2
Torsional Central vestibular/CNS disorders Ocular motor dysfunction/palsy
Others (Ocular oscillations & flutters, Pendular nystagmus) Central vestibular/CNS disorders Vestibular migraine Inconclusive
1 1 Total = 2
1 1 2 Total = 4
4. Discussion With the aid of VNG, we were able to document spontaneous nystagmus in a relatively large group of pediatric patients. Although the overall percentage of our patients identified with spontaneous nystagmus is not particularly high, around 15%, we feel that the detection and characterization of the spontaneous nystagmus was very helpful in establishing a clinical diagnosis. We first looked at the effect of visual fixation on spontaneous nystagmus for interpretation, following an established routine [5]. Similar to published studies, we noticed spontaneous nystagmus that can be suppressed by visual fixation presented more often in peripheral vestibular disorders, such as vestibular neuritis and labyrinthitis, while non-suppressible spontaneous nystagmus presented more often in central disorders [1,3,14,16,24,26,35]. We did observe that fixation suppression of spontaneous nystagmus varied among patients with a diagnosis of vestibular migraine. Although vestibular migraine has generally been thought to occur primarily within the brain itself [36–38], numerous studies have also shown evidence of variable degrees of peripheral vestibular dysfunction in adult patients with vestibular migraine [39–44]. Such peripheral vestibular impairment has been theorized to occur in vestibular migraine patients via
Fig. 3. Variable spontaneous nystagmus in patients with vestibular migraine. The Y-axis represents the actual number of patients, and the percentages over the bars are out of the total 21 patients with vestibular migraine.
direct effects of the trigemino-vascular pathway on the peripheral vestibular organs [45–48]. Our findings further support this increasingly popular theory that vestibular migraine may have effects on both 105
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Fig. 4. Distribution of diagnoses of common vestibular disorders (vestibular migraine, peripheral & central vestibular disorders) in all 86 patients.
nystagmus, a discussion with an ophthalmologist may be beneficial.
the brain and the inner ear. Our next focus on spontaneous nystagmus was regarding direction. Different from previous reports of spontaneous nystagmus in children being only horizontal [27], the complexity of direction of spontaneous nystagmus in children is evident in our study. As expected, fixed-direction horizontal spontaneous nystagmus was the most common (50% of the total patients). This type of spontaneous nystagmus may be present in many patients with peripheral vestibular disorders. Nonetheless, we only found about 35% (15 out of 43) of patients were diagnosed with peripheral vestibular disorders in our study. Therefore, other diagnoses such as central vestibular disorders or vestibular migraine can't be ruled out in this situation. Oblique/diagonal spontaneous nystagmus was the second most frequently documented, in about 23% of patients, and these patients had quite diverse diagnoses. Pure down-beating spontaneous nystagmus is commonly associated with brainstem and cerebellar lesions [21–23]. About 15% of our patients had this type of spontaneous nystagmus, and some of these patients were found to have a cerebellar lesion such as a Chiari I malformation, but others were diagnosed with vestibular migraine, again supporting the potentially diffuse impacts of vestibular migraine. The diagnostic value of spontaneous nystagmus has been controversial since spontaneous nystagmus was reportedly seen in some normal subjects [1,49,50]. However, in our study, we found spontaneous nystagmus recorded by VNG in pediatric patients with vestibular complaints or symptoms to be a pathologic finding in nearly all cases, with the exception of just two cases. While the presence of spontaneous nystagmus alone can't be used to make a diagnosis of vestibular disorder, we have found the presence and characteristics of spontaneous nystagmus to be a valuable complement to a comprehensive history and examination and other vestibular testing results in determining the cause of pediatric patients vestibular symptoms. For example, 50% of our patients with spontaneous nystagmus were eventually diagnosed with either vestibular migraine or peripheral vestibular disorders. Limitations of our study include the retrospective format and lack of a normal subject group for comparison. Although we chose the primary diagnosis in our analysis, some patients had more than one clinical diagnosis, which may complicate presenting nystagmus. Even with our best efforts and all available exam outcomes, we could not make a definitive diagnosis in 6 cases, which we called inconclusive. Interpretation and diagnosis of rarely-seen spontaneous nystagmus such as torsional and direction-alternating nystagmus warrant extra caution. In cases with ocular oscillations and flutters that mimic spontaneous
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