Neurol Sci DOI 10.1007/s10072-015-2219-9
ORIGINAL ARTICLE
Patient-reported Chiari malformation type I symptoms and diagnostic experiences: a report from the national Conquer Chiari Patient Registry database Rebecca Fischbein1 • Julia R. Saling2 • Paige Marty2 • Denise Kropp2 James Meeker2 • Jenna Amerine3 • Michelle Renee Chyatte2
•
Received: 5 November 2014 / Accepted: 15 April 2015 Ó Springer-Verlag Italia 2015
Abstract Chiari malformation (CM) is a condition in which cerebellar tonsillar ectopia may manifest with various clinical presentations. This study reports from the only national, online patient registry available, the symptoms, comorbid neurocognitive and psychological conditions, and diagnostic experiences of patients living with CM type I (CM I). The current research is one component of a large investigation designed to collect information from individuals with CM through the online Conquer Chiari Patient Registry questionnaire. Analyses included descriptive statistics to study body system impact and patient diagnostic experiences. Participants were 768 individuals with CM I and were predominantly female (86.8 %) and Caucasian (93.8 %) with an average age of 35 years. Pain was the most frequently reported symptom (76.69 %) experienced prior to diagnosis with headaches implicated most often (73.44 %). Neurocognitive comorbidities included memory difficulties (43.88 %) and aphasia (43.75 %) and psychological disorders such as depression (31.77 %) and anxiety disorders (19.92 %) were reported. Average time to diagnosis from first physician visit to diagnosis was 3.43 years, and only 8.46 % of patients had previous awareness of CM. CM I diagnosis was found incidentally for 24.87 % of participants. Common misdiagnoses were
& Rebecca Fischbein [email protected] 1
Department of Health Policy and Management, College of Public Health, Kent State University, 210 Moulton Hall, Kent, OH 44242, USA
2
Northeast Ohio Medical University, 4209 St. Rt. 44, PO Box 95, Rootstown, OH 44272, USA
3
Trumbull County Health Department, 176 Chestnut Ave NE, Warren, OH 44483, USA
classified as psychological (19.26 %) and neurological (19.26 %). Fear was the most frequent emotion elicited at the time of correct diagnosis (42.19 %). CM I can be a challenging condition for patients and physicians, during both the search for diagnosis and management of symptoms. Patient and physician education about CM I may permit early intervention and the prevention of further deterioration and patient suffering. Keywords Chiari malformation Symptomatology Diagnostic experience Registry
Introduction Chiari malformation (CM) is characterized by cerebellar herniation through the foramen magnum and potentially into the upper portion of the spinal canal [1]. Possible CM etiologies include genetic predisposition, congenital anomalies, and acquisition through trauma or illness [2]. Four types of CM (CM I, CM II, CM III, CM IV) are differentiated according to cerebellar herniation, spinal cord spacing, and severity of the disorder with most cases of CM II, III, and IV identified before birth or in early infancy [3]. CM I, however, is typically diagnosed in adulthood [4, 5] although manifestation also appears in younger populations [6]. While the exact prevalence remains unknown [6], an estimated 215,000 Americans are believed to have CM I making it the largest population of CM types [3]. CM I is a complex neurological disorder, categorized by symptomatology that often leads to debilitating headaches, neck pain, dizziness, and visual disturbances [7]. Diagnosis is made via neuroimaging techniques, specifically with the use of magnetic resonance imaging (MRI). Incidental CM I
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diagnoses are increasingly common as the use of diagnostic MRIs [8, 9] becomes more frequent, especially for children [6]. One-third to one-half of children may be asymptomatic at the time of CM I diagnosis [8], while a higher percentage of adults show symptoms (70–86 %) [10, 11]. CM I symptoms often overlap with other disorders, including fibromyalgia and chronic fatigue [12], making it difficult to distinguish CM I from other similarly manifesting disorders. Only a few studies have examined trends regarding the symptoms and diagnosis of CM I. Milhorat et al. [5] clinically examined and interviewed 364 patients with CM I between 1994 and 1997. The most frequent symptom was suboccipital headaches (81 %), and more than one-third of the group (37 %) indicated lifelong symptoms. Twentyfour percent of individuals reported the onset of symptoms due to physical trauma. The majority (59 %) of participants reported being misdiagnosed as having a mental or emotional problem. A study by Mueller and Oro [13] assessed patient-reported symptomatology of 265 patients diagnosed with CM I via MRI between 1999 and 2002. Mueller and Oro [13] found 98 % of patients presented with headache, followed by dizziness (84 %) and difficulty sleeping (72 %). In addition to headache and dizziness, the researchers report the following distinguishing CM I symptoms: neck pain and pressure, feelings of burning in the neck, exhaustion, and weakness. Since the work by Milhorat et al. [5] and Mueller and Oro [13], no sizable research has examined CM I symptomatology and diagnostic process using patient-reported data. It is important to understand and disseminate patientreported symptoms and experiences prior to and during the CM I diagnostic process to facilitate early and accurate diagnosis. Consequently, the current study contributes to the small but growing body of information of patients’ with CM I symptomatology and diagnostic experiences using the largest online patient CM registry. To better understand the complex nature and impact of CM I on patients, the United States-based Conquer Chiari Foundation and Conquer Chiari Research Center developed and implemented a voluntary online patient registry. As of April 2014, 957 unique individuals have logged onto the website and entered data pertaining to CM representing the largest national database of CM patients. The current study examines symptomatology and diagnostic information as reported in the registry by patients living with CM I.
is advertised to patients and patient caregivers via multiple methods including on the Conquer Chiari Research website. Interested individuals register with the website and complete questionnaires on multiple topics including: demographics and family background, symptoms, related conditions, treatments including pharmaceutical, surgical, and complementary alternative medicine, and impact of CM on psychosocial life areas. Participants in the registry must be diagnosed by a physician or from an MRI with a tonsillar descent of at least 5 mm. Participants must be at least 18 years of age or parents or guardians of patients under age eighteen with CM. Data included in this study were entered into the registry between August 2012 and April 2014. This work was approved by the institutional review boards of both (The University of Akron) and (Northeast Ohio Medical university). Instruments Similar to Milhorat [5] and Mueller and Oro [13], symptomatology was assessed at systems level (e.g., neurological, vestibular, visual, auditory, gastrointestinal). Participants were asked to indicate if they experienced a symptom just prior to diagnosis. More detailed information was obtained regarding the manifestations of common symptoms (pain, headache, numbness, weakness). Neurocognitive and psychological symptoms and diagnoses were also gathered. Diagnostic information included items assessing age at diagnosis, incidental versus actively sought diagnosis, time to diagnosis, specialties of physicians visited and misdiagnosis for those who actively sought a diagnosis, and reasons an MRI was performed for those diagnosed incidentally. Finally, demographic information included questions regarding age, gender, race, and associated conditions. Statistics Data were extracted from the dynamic, online patient registry database and imported into SPSS version 22 (IBM/ SPSS, Inc., Chicago, IL). Statistical analyses included descriptive statistics such as means and frequencies. For open-ended questions, qualitative data were coded into like categories.
Results Methods The current research is one component of an investigation designed to collect information from individuals with CM through the Conquer Chiari Patient Registry. The registry
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Registry participants were included in the analysis if they were diagnosed with CM I by a physician or by MRI findings and reported as a patient or the parent of a patient with CM I. This reduced the sample size of the current study from 957 to 768 registry participants.
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Clinical presentation Table 1 details patient registry demographics. Scoliosis was the most frequently reported related condition (25.39 %), followed by syringomyelia (24.05 %) and pseudotumor cerebri/intracranial hypertension (8.72 %). The most common incident to trigger onset of CM I symptoms was a car accident (5.34 %), followed by other head trauma (3.91 %), falling (2.86 %), pregnancy (2.34 %), and other events (8.07 %). Approximately 25 % of participants reported that their CM I diagnosis was found incidentally. The most commonly reported reasons for an incidental diagnosis were headache (26.55 %), receiving a CT or MRI while trying to verify another cause
Table 1 Patient information No. CM I
% CM I (n = 768)
Demographics Gender Female
630
82.03
Missing
42
12.31
Age [mean years (SD)]
35.0 (14.8)
Race White Black
670 12
87.24 1.56
American Indian
25
3.26
Alaska Native
0
0
Native Hawaiian
0
0
Other Pacific Islander
0
0
Asian
6
0.78
Other
10
1.30
Multiracial
7
0.91
Missing
38
4.95
Clinical presentation Age of onset [mean years (SD)]
20.7 (13.7)
Age at diagnosis [mean years (SD)]a
32.7 (14.5)
Knowledge of CM I prior to diagnosis
Symptomatology Just prior to diagnosis, patients with CM I reported a variety of systems affected by CM I symptoms (Table 2). Physical labor (20.42 %), changes in the weather (15.15 %), and stress (13.64 %) were reported as precipitating factors that exacerbated symptoms (data not shown; available on request). Pain was the most frequently reported symptom experienced prior to diagnosis (Table 3) with headaches the highest implicated pain type (Table 4). The most common location for headaches was at the back of the head though many participants also noted headache location behind the eyes. Multiple events were indicated as precipitating headache onset with coughing and bending over as the highest reported. Headaches (47.30 %) were most frequently reported as the worst symptom prior to diagnosis, followed by pain throughout the entire body (5.98 %) and neck and shoulder pain (4.27 %). The worst symptoms prompting patients to go to the doctor included headaches (51.38 %), syncope (4.86 %), and dizziness (4.17 %) (data not shown; available on request). Associated findings Neurocognitive and psychological comorbidities were seen in a number of patients with CM I prior to CM I diagnosis (Table 5). Approximately 44 % of participants indicated experiencing memory problems as well as aphasia prior to initial diagnosis. Depression was the most commonly reported diagnosed mood disorder (31.77 %), and almost 20 % of patients reported being diagnosed as having some type of anxiety disorder.
Yes
65
8.46
No Missing
398 305
51.82 39.71
Diagnostic experience For participants who reported that they had actively sought a diagnosis, primary care physicians/family doctors (35.83 %), neurologists (38.76 %), and neurosurgeons (43.97 %) were the most common specialties patients visited at least once during the diagnostic process (Table 6). Also for patients who reported that they had actively sought a diagnosis, average time to diagnosis was 3.43 years, as calculated from first physician visit date to diagnosis date (Table 1). There were 135 patients actively seeking diagnoses who experienced misdiagnoses. The two
Actively seeking diagnosis
307
39.97
Incidental diagnosis
191
24.87
270
35.16
Missing Time to diagnosis [mean years (SD)]b
3.43 (5.23)
a
Some dates were reported by patients in month/year only. In these cases, the patient registry database assigned the day as the first of the month. Therefore, calculated time variables (age at diagnosis, time to diagnosis) should be interpreted as ±60 days
b
for CM I symptoms (15.82 %), such as multiple sclerosis and pain in the neck, shoulders, or arms. Numbness, tingling, and burning (8.47 %) also led to incidental diagnosis as well as eye complications (6.78 %) and a variety of other unique causes (46.89 %) (data not shown; available on request).
n = 182 patients actively seeking diagnosis. Forty-nine patients were removed from the analysis due to issues with date reporting
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Neurol Sci Table 2 Symptomatology prior to diagnosis No. CM I Ear
% CM I (n = 768)
327
42.58
Fullness in ears
193
25.13
Tinnitus
261
33.98
Ear pain
159
20.70
Hearing loss
123
37.61
Sensitivity to loud noises
242
31.51
Vestibular system
351
45.70
Dizziness
275
35.81
Vertigo
200
26.04
Balance problems Nystagmus Eyes
281
36.59
122 452
15.89 58.85
Blurred vision
325
42.32
Double vision
174
22.66
Sensitivity to light
353
45.96
Strabismus
38
4.95
341
44.40
Trouble swallowing
254
33.07
Abnormal gag reflex
175
22.79
Hoarse voice
176
22.92
Gastrointestinal
226
29.43
Nausea
211
27.47
Vomiting
110
14.32
Throat
Failure to thrive (children) Trouble sleeping Sleep apnea Obstructive Central Mixed Other
12
1.56
439
57.16
77
10.03
39 21
5.08 2.73
17
2.21
503
65.49
Abnormal sweating
197
25.65
Inability to regulate temperature
273
35.55
Bladder problems
242
31.51
Bowel problems
220
28.65
Fainting/blackouts
180
23.44
Fatigue
454
59.11
Shortness of breath
266
34.64
most common types of misdiagnoses were psychological and neurological disorders (Table 7). The most common emotion experienced during the time of diagnosis was fear (42.19 %) followed by a sense of being overwhelmed (40.23 %), shock (38.08 %), relief (35.16 %), resolve (24.61 %), sadness (21.09 %), and anger (16.05 %) with resignation being the least reported (4.30 %). Some patients noted frustration at the delay in diagnosis, as exemplified by the participant comment: ‘‘Why so many years to find this?’’ Interestingly, only
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8.46 % of patients indicated that they had previously heard of CM I or knew anyone with the condition.
Discussion CM is a complex disorder with an etiology that is not yet fully understood. Comparable to the work by Milhorat [5], the current research presents the patient-reported events that triggered CM I symptoms. Similar rates of women report pregnancy as a triggering symptom onset in the work by Milhorat [5] and the current research (2.4 and 2.3 %, respectively). Consequently, pregnancy may be a concern for some women already diagnosed with CM I. However, Mueller and Oro [14] report that, among seven pregnant women diagnosed with CM I either prior to or at the time of pregnancy, none displayed significant increases in symptoms during or after delivery. Another similarity between the work of Milhorat [5] and the current study regarding symptom onset is the reporting of trauma as a symptom-triggering incident. The current study found that trauma from car accident (5.3 %), other head trauma (3.9 %), and falls (2.7 %) were the most commonly reported trauma-related triggering factors. Milhorat [5] reported that 18.3 % of patients indicated whiplash and direct hits to the neck and head as a trigger for symptom onset. A chart review by Wan et al. [15] on 85 patients revealed that 12.9 % of patients sustained minor head or neck trauma prior to symptom onset. When stricter inclusion criteria were used to determine whether trauma was truly a causal factor for symptom onset, the number of cases with traumaattributable onset was reduced to 3.5 %. This finding suggests a discrepancy between the self-reported work by Milhorat et al. [5] and the current research with that of the chart review methodology used by Wan et al. [15]. However, direct comparisons between the results of the current research and those of Milhorat et al. [5] to the work of Wan et al. [15] are difficult as neither Milhorat nor the current research assessed the severity of the trauma. Further, the self-report nature of the work by Milhorat et al. [5] and the current research limits the ability to identify the exact precipitating factors for symptom onset. Recent research has also attempted to understand the natural history of CM I by exploring symptomatology and associated neuroanatomical manifestations. Symptomatology is variable, causing otoneurological, optical, respiratory, psychological, and cognitive effects [1, 3–5, 7, 9, 16, 17]. Prior work has demonstrated that the most common symptom of CM I is a suboccipital headache exacerbated by physical exertion [5, 13]. Likewise, in this study the most common symptom was a headache located in the back of the head with exercise and physical labor commonly reported as the precipitating event. Another
Neurol Sci Table 3 Pain, weakness, and numbness localization prior to diagnosis No. CM I Pain (pain and headaches combined)
% CM I (n = 768)
589
76.69
Headaches
564
73.44
Neck Shoulders
472 394
61.46 51.30
Upper back
254
33.07
Middle back
161
20.96
Lower back
274
35.68
Arms
229
29.82
Hands
205
26.69
Legs
222
28.91
Feet
172
22.40
452
58.85
Right arm
246
32.03
Right hand
322
41.93
Right leg
150
19.53
Right foot
207
26.95
Left arm
252
32.81
Left hand Left leg
300 173
39.06 22.53
Left foot
218
28.39
Weakness
405
52.73
right arm
238
30.99
Right hand
238
30.99
Right leg
171
22.27
Right foot
111
14.45
Left arm
250
32.55
Left hand
236
30.73
Left leg
196
25.52
Left foot
122
15.89
Numbness/tingling
similarity to previous work [5, 13] was the frequently reported symptom of ocular disturbances with common examples being sensitivity to light, blurred vision, and double vision. Consistent with the work by Mueller and Oro [13], the current research found that the patients experienced multiple neurocognitive and psychological comorbidities. Depression, anxiety, and problems with decision making are important elements for healthcare providers to consider in their delivery of medical care and advice [18]. For example, headache, one of the most frequently reported symptoms in this survey, causes disruptions that decrease quality of life [19, 20]. The more quickly and accurately a patient receives diagnosis and treatment, the better he or she can manage symptoms and return to a normal lifestyle [19]. The overlapping of CM I symptoms with those of other disorders complicates differential diagnosis. One such
symptom is headache. Currently, there are no criteria specific to a headache that is attributable to CM I [21]. Furthermore, it has not been suggested that CM I induces headache [22]. Clinicians should be encouraged to perform comprehensive physical, neurological, and mental status examinations, as well as evaluation of non-clinical factors to correctly determine the cause of headache [21]. CM I could also be mistaken for other disorders, even if tonsillar descent has been discovered on an MRI [22]. Two examples are intracranial hypotension (pseudo-Chiari) and intracranial hypertension secondary to hydrocephalus [22]. Patients with these conditions present symptoms congruent with CM I. Further, CM I can complicate the differential diagnosis of postdural puncture headache at parturition [23]. This is because CM I symptoms frequently begin at child-bearing age or CM I can be acquired from administration of neuraxial anesthesia [23]. Similar to the results reported by Milhorat et al. [5], the current research reveals that frequent misdiagnoses were psychological and neurological in origin with the most common being depression, stress/anxiety, multiple sclerosis, and psychogenic issues. Patient experience during the search for correct diagnosis of CM I mirrors that of individuals suffering from rare disease [24]. In the current research, patients experienced diagnostic delay, lack of prior knowledge about CM I, and a variety of misdiagnoses. Diagnosis is further complicated by the lack of agreement as to what constitutes CM I [25]. There are discrepancies in scientific literature as to what neural and/or other structural abnormalities define this disorder. CM I is conventionally defined as a downward descent of the cerebellar tonsils of at least 5 mm below the foramen magnum [3]. However, other sources state that this descent can be as small as 3 mm [16]. Additionally, it has been stated that tonsillar descent of greater than 12 mm is associated with the presence of CM I symptoms and that, while nearly 1 % of adults may have radiographic evidence of a tonsillar descent greater than 5 mm, only 0.01–0.04 % of those with this evidence actually manifest symptoms indicative of CM I [2]. Because the information from this survey was gained through selfreport, we do not have information about what specific criteria physicians used to diagnose the CM I in these participants. Delay in CM I diagnosis can have serious implications with diagnosis later in life related to an increased risk for severe headache syndrome, neck pain, vertigo, or ataxia [6]. It is recommended that patients who have CM I presenting with progressive or intractable symptoms and/or expanding syringomyelia receive surgery as soon as possible in order to prevent further surgical deterioration [2]. Proper surgical intervention may result in complete decompression of the medulla oblongata, improving clinical symptoms [17]. Over one-third of the patients in this
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Neurol Sci Table 4 Headaches and precipitating headache onset as a pain subset No. CM I
% CM I (n = 768)
564
73.44
Back of the head
386
50.26
Top of the head
101
Headache
Right side of the head Left side of the head Front of the head
Table 5 Neurocognitive diagnosis
and
psychological
findings
% CMI (n = 768)
Memory problems
337
43.88
13.15
Aphasia
336
43.75
13.67
Problems with decision making
243
31.64
89
11.59
Problems planning
224
29.17
151
19.66
Personality disorder
15
1.95
34
4.43
105
Behind the eyes
206
26.82
Deep inside the head
115
14.97
All over
181
23.57
Learning disorder Mood disorder
54 267
7.03 34.77
Depression
244
31.77
1
0.13
12
1.56
Headache precipitating event Coughing Sneezing
362 311
Laughing
47.14 40.49
Adjustment disorder Bipolar disorder
262
34.11
Mood disorder NOS
4
0.52
Singing
94
12.24
Anger
1
0.13
Talking
75
9.77
Major depressive disorder
3
0.39
2
0.26
Bending over
361
47.01
PMS
Change in position
247
32.16
Anxiety disorders
153
19.92
79
10.29 2.21
Exercise
315
41.02
Anxiety
Desk work
125
16.28
PTSD
17
40.89
GAD
20
2.60
5
0.65
3
0.39
2 21
0.26 2.73
314
Sexual activity
123
16.02
Social anxiety
Nothing specific
154
20.05
ADHD
13.41
Agoraphobia Panic attacks/disorder
Other
103
registry who actively pursued a diagnosis saw at least one primary care provider. Findings have indicated that the usage of an MRI for patients experiencing headache is costly and typically yields little significant, clinical results [20]. This lack of utility may lead to few primary care physician referrals to imaging services which could provide the CM I diagnosis. There are several factors that can influence referral to imaging services when the chief complaint is a headache [26]. Some of these factors include access to resources, training of medical staff, and disparities due to patient demographics [26]. Patient and physician education about CM I will help improve the diagnosis timeline, potentially reduce misdiagnoses, and allow for early intervention to prevent further deterioration and needless patient suffering. The voluntary, self-reporting nature of the registry yielded unique insight into CM I. Although the results of the current research replicate many of the findings regarding CM I clinical presentation, symptomatology, and diagnosis [5], data were self-reported and therefore subjective. In addition, the web-based nature of the registry may have limited the generalizability of the current research. Minorities, individuals in rural areas, and women are less likely to have home computers and internet access [27] and may have been underrepresented in the registry. Our study
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to
No. CM I
Obsessive compulsive disorder
Physical labor
prior
included a large sample of women (82.03 %) which is similar to other CM I studies that have used samples with predominantly female patients [5, 28, 29]. Minorities, however, were significantly underrepresented compared to the expansive Caucasian sample (87.24 %). It is impossible to know if minority representation is reflective of those affected with CM I due to underrepresentation of minorities in research [30, 31] and the lack of including race and ethnicity within demographic information in previous CM I studies [for example, 5, 28, 29]. In addition, findings have shown that primary care physicians who treat African American patients have more difficulty accessing diagnostic imaging services and medical specialists of high quality in comparison to those physicians who treat Caucasian patients [32]. The challenges with diagnosis and treatment faced by African Americans patients may be reflected in their underrepresentation in the current research.
Conclusion Using a large sample of 768 registry participants, the current study adds to the existing literature by providing patient-reported CMI I symptomatology and clinical
Neurol Sci Table 6 Frequency of CM I patients who saw specialty at least once during diagnostic process Specialty
No. CM I
% CMI (n = 307a)
Ear/nose/throat
22
7.17
Endocrinologist
4
1.30
Gastro intestinal specialist Neuro-ophthalmologist
5 5
1.63 1.63
Neurologist
119
38.76
Neurosurgeon
135
43.97
5
1.63
Ophthalmologist
10
3.26
Orthopedic surgeon
14
4.56
Obstetrician/gynecologist
Pain specialist
14
4.56
Pediatric neurologist
17
5.54
Pediatric neurosurgeon
23
7.49
Pediatrician
15
4.89
Physiatrist
3
0.98
110
35.83
Psychiatrist
4
1.30
Psychologist
1
0.33
17
5.54
44
14.33
Primary care physician/family doctor
Rheumatologist Otherb a
Patients actively seeking diagnosis
Table 7 Patient-reported misdiagnoses No. CM I
% CMI (n = 135a)
Psychologicalb
26
19.26
Neurologicalc
26
19.26
Chronic fatigue syndrome
16
11.85
d
Autoimmune
15
11.11
Spinal abnormalitye
8
5.93
Musculoskeletalf
8
5.93
Respiratoryg
5
3.70
Cardiovascularh
5
3.70
Vestibulari
4
2.96
Sinus
4
2.96
Visualj Infectionk
3 2
2.22 1.48
Overweight
2
1.48
Pseudotumor
2
1.48
Misappropriated pain
2
1.48
Inflammation
1
0.74
Thyroid disorder
1
0.74
Anemia
1
0.74
Vitamin D deficiency
1
0.74
l
Normal
1
0.74
Reflux
1
0.74
Allergies
1
0.74
b
Patients reported the following other specialties: Cardiologist, chiropractor, ER doctor, pulmonologist, sleep doctor, asthma and allergy doctor, general practitioner, internal medicine, DO, urologist, physician assistant, referral specialist doctor, pediatric orthopedic surgeon, urgent care doctor, hematologist, hand specialist, nurse practitioner, radiologist, spine specialist, stroke/TIA, hernia specialist, sports chiropractic, orthopedist, infectious disease doctor, geneticist, cerebrovascular disease, speech therapist
a
135 patients actively seeking a diagnosis who reported experiencing a misdiagnosis
b
Psychogenic (3), bipolar (1), depression (10), stress/anxiety (12)
c
Cerebral palsy (2), MS (5), myasthenia gravis (1), non-specific brain change (1), concussion (1), essential tremor (1), headache/migraine (15)
d
Lupus (5), other (10) Bulging/herniated disk (3), spondylosis (1), degenerated/slipped disk (1), spinal misalignment (1), craniocervical syndrome (1), tethered cord (1)
e
presentation. Despite advancements in understanding disease process, origin, and symptomatology in the past 15 years [2, 16, 33, 34], patients continue to experience delays in diagnosis as well as misdiagnoses. The current research sheds light on some of these diagnostic experiences. One-third of patients saw at least one primary care physician during the search for the diagnosis. Most patients were diagnosed with a disorder of which they had no prior knowledge, experienced a myriad of emotions upon diagnosis, and many had comorbid psychological diagnoses that may have complicated the CM I diagnostic and management process. Further research is needed to determine the impact of the patient–physician relationship throughout the disease time course as well as the effectiveness of various specialties in the diagnosis and management of CM I as a whole. Patient and physician education about CM I
f
Facet syndrome (1), muscle strain (2), osteopenia (1), sesamoiditis (1), ‘‘stress walk’’ (1), fibromyalgia (2)
g
Stridor (1), laryngomalacia (1), epiglottis malacia (1), breathholding spells (1), sleep apnea (1)
h
TIA (2), vasodepressive presyncope (1), pericardial effusion (1), hypertension (1)
i
BPPV (1), Meniere’s disease (2), vestibular neuritis (1)
j
Strabismus (1), papilledema (1), poor vision (1)
k
Syphilis (1), meningitis (1)
l
Residual pain from accident (1), reflex sympathetic dystrophy (1)
may help reduce diagnosis delay, allowing for early intervention and the prevention of further deterioration and needless patient suffering.
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Neurol Sci Acknowledgments We wish to thank the patients and caregivers of patients with CM who provided information on the registry. We also wish to thank the Conquer Chiari Foundation and especially Rick Labuda who designed the patient registry and recruited patient participants. Without his efforts, this research would not be possible.
14.
15. Conflict of interest of interest.
The authors declare that they have no conflict 16.
Ethical standard All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
17.
18. Informed consent Informed consent was obtained from all individual participants included in the study. 19.
References 1. National Institute of Neurological Disorders and Stoke. Chiari malformation fact sheet. http://www.ninds.nih.gov/disorders/ chiari/detail_chiari.htm. Accessed 1 June 2014 2. Heiss J (2013) Epidemiology of the Chiari I malformation. In: Tubbs RS, Oakes WJ (eds) The Chiari malformations. Springer Science ? Business Media, New York, pp 83–92 3. Speer MC, Enterline DS, Mehltretter L, Hammock P, Joseph J, Dickerson M et al (2014) Chiari type i malformation with or without syringomyelia: prevalence and genetics. J Genet Couns 12(4):297–311 4. Dyste GN, Menezes AH, VanGilder JC (1989) Symptomatic Chiari malformations. An analysis of presentation, management, and long-term outcome. J Neurosurg 71(2):159–168 5. Milhorat TH, Chou MW, Trinidad EM, Kula RW, Mandell M, Wolpert C et al (1999) Chiari I malformation redefined: clinical and radiographic findings for 364 symptomatic patients. Neurosurgery 44(5):1005–1017 6. Aitken LA, Lindan CE, Sidney S, Gupta N, Barkovich AJ, Sorel M et al (2009) Chiari type I malformation in a pediatric population. Pediatr Neurol 40(6):449–454 7. Fernandez AA, Guerrero AI, Martinez MI, Vazquez ME, Fernandez JB, Octavio CI et al (2009) Malformations of the craniocervical junction (Chiari type I and syringomyelia: classification, diagnosis and treatment). BMC Musculoskelet Disord 10(Suppl 1):S1–S11 8. Wu YW, Chin CT, Chan KM, Barkovich AJ, Ferriero DM (1999) Pediatric Chiari I malformations: do clinical and radiologic features correlate? Neurology 53(6):1271–1276 9. Genitori L, Peretta P, Nurisso C, Macinante L, Mussa F (2000) Chiari type I anomalies in children and adolescents: minimally invasive management in a series of 53 cases. Childs Nerv Syst 16(10–11):707–718 10. Meadows J, Kraut M, Guarnieri M, Haroun RI, Carson BS (2000) Asymptomatic Chiari type I malformations identified on magnetic resonance imaging. J Neurosurg 92(6):920–926 11. Elster AD, Chen MY (1992) Chiari I malformations: clinical and radiologic reappraisal. Radiology 183(2):347–353 12. Ellenbogen R, Bauer D (2013) Association between fibromyalgia, chronic fatigue, and the Chiari I malformation. In: Tubbs RS, Oakes WJ (eds) The Chiari malformations. Springer Science ? Business Media, New York, pp 265–271 13. Mueller DM, Oro JJ (2004) Prospective analysis of presenting symptoms among 265 patients with radiographic evidence of
123
20.
21.
22.
23.
24. 25. 26.
27. 28. 29.
30. 31.
32.
33.
34.
Chiari malformation type I with or without syringomyelia. J Am Acad Nurse Pract 6(3):134–138 Mueller DM, Oro JJ (2005) Chiari I malformation with or without syringomyelia and pregnancy: case studies and review of the literature. J Am Perinatol 22(2):67–70 Wan MJ, Nomura H, Tator CH (2008) Conversion to symptomatic Chiari I malformation after minor head or neck trauma. Neurosurgery 63:748–753 Schijman E (2004) History, anatomic forms, and pathogenesis of Chiari I malformations. Childs Nerv Syst 20(5):323–328 Zhang ZQ, Chen YQ, Chen YA, Wu X, Wang YB, Li XG (2007) Chiari I malformation associated with syringomyelia: a retrospective study of 316 surgically treated patients. Spinal Cord 46(5):358–363 Martin LR, Williams SL, Haskard KB, Dimatteo MR (2005) The challenge of patient adherence. Ther Clin Risk Manag 1(3):189–199 Ryan RE Jr, Pearlman SH (2004) Common headache misdiagnoses. Prim Care Clin Office Pract 31(2):395–405 Jordan JE, Ramirez GF, Bradley WG, Chen DY, Lightfoote JB, Song A (2000) Economic and outcomes assessment of magnetic resonance imaging in the evaluation of headache. J Natl Med Assoc 92(12):573–578 Grazzi L, Andrasik F (2012) Headaches and Arnold-Chiari syndrome: when to suspect and how to investigate. Curr Pain Headache Rep 16(4):350–353 Mea E, Chiapparini L, Leone M, Franzini A, Messina G, Bussone G (2011) Chronic daily headache in the adults: differential diagnosis between symptomatic Chiari I malformation and spontaneous intracranial hypotension. Neurol Sci 32(Suppl 3):S291– S294 Brown JP, Lea DE, Douglas MJ (2013) Acquired Chiari I malformation: a differential diagnosis in severe postdural puncture headache? Int J Obstet Anesth 22(1):81–83 Kole A, Faurisson F (2010) Rare diseases social epidemiology: analysis of inequalities. Adv Exp Med Biol 686:223–250 Proctor MR, Scott RM, Oakes WJ, Muraszko KM (2011) Chiari malformation. Neurosurg Focus 31(3) Introduction Couchman GR, Forjuoh SN, Rajab MH, Phillips CD, Yu J (2004) Nonclinical factors associated with primary care physicians’ ordering patterns of magnetic resonance imaging/computed tomography for headache. Acad Radiol 11(7):735–740 Wilson K, Reiser K (2003) Social stratification and the digital divide. Soc Sci Comp Rev 21:133–143 Lewis AR, Kline LB, Sharpe JA (1996) Acquired esotropia due to Arnold-Chiari I malformation. J Neuroophthalmol 16(1):49–54 Kaplan Y, Oksuz E (2008) Chronic migraine associated with the Chiari type 1 malformation. Clin Neurol Neurosurg 110(8):818–822 Svensson CK (1989) Representation of American blacks in clinical trials of new drugs. JAMA 261(2):263–265 Hussain-Gambles M, Atkin K, Leese B (2004) Why ethnic minority groups are under-represented in clinical trials: a review of the literature. Health Soc Care Community 12(5):382–388 Bach PB, Pham HH, Schrag D, Tate RC, Hargraves JL (2004) Primary care physicians who treat blacks and whites. N Engl J Med 351(6):575–584 Christophe C, Dan B (1999) Magnetic resonance imaging cranial and cerebral dimensions: is there a relationship with Chiari I malformation? A preliminary report in children. Eur J Paediatr Neurol 3(1):15–23 Tubbs RS, McGirt MJ, Oakes WJ (2003) Surgical experience in 130 pediatric patients with Chiari I malformations. J Neurosurg 99(2):291–296
ORIGINAL ARTICLE
Patient-reported Chiari malformation type I symptoms and diagnostic experiences: a report from the national Conquer Chiari Patient Registry database Rebecca Fischbein1 • Julia R. Saling2 • Paige Marty2 • Denise Kropp2 James Meeker2 • Jenna Amerine3 • Michelle Renee Chyatte2
•
Received: 5 November 2014 / Accepted: 15 April 2015 Ó Springer-Verlag Italia 2015
Abstract Chiari malformation (CM) is a condition in which cerebellar tonsillar ectopia may manifest with various clinical presentations. This study reports from the only national, online patient registry available, the symptoms, comorbid neurocognitive and psychological conditions, and diagnostic experiences of patients living with CM type I (CM I). The current research is one component of a large investigation designed to collect information from individuals with CM through the online Conquer Chiari Patient Registry questionnaire. Analyses included descriptive statistics to study body system impact and patient diagnostic experiences. Participants were 768 individuals with CM I and were predominantly female (86.8 %) and Caucasian (93.8 %) with an average age of 35 years. Pain was the most frequently reported symptom (76.69 %) experienced prior to diagnosis with headaches implicated most often (73.44 %). Neurocognitive comorbidities included memory difficulties (43.88 %) and aphasia (43.75 %) and psychological disorders such as depression (31.77 %) and anxiety disorders (19.92 %) were reported. Average time to diagnosis from first physician visit to diagnosis was 3.43 years, and only 8.46 % of patients had previous awareness of CM. CM I diagnosis was found incidentally for 24.87 % of participants. Common misdiagnoses were
& Rebecca Fischbein [email protected] 1
Department of Health Policy and Management, College of Public Health, Kent State University, 210 Moulton Hall, Kent, OH 44242, USA
2
Northeast Ohio Medical University, 4209 St. Rt. 44, PO Box 95, Rootstown, OH 44272, USA
3
Trumbull County Health Department, 176 Chestnut Ave NE, Warren, OH 44483, USA
classified as psychological (19.26 %) and neurological (19.26 %). Fear was the most frequent emotion elicited at the time of correct diagnosis (42.19 %). CM I can be a challenging condition for patients and physicians, during both the search for diagnosis and management of symptoms. Patient and physician education about CM I may permit early intervention and the prevention of further deterioration and patient suffering. Keywords Chiari malformation Symptomatology Diagnostic experience Registry
Introduction Chiari malformation (CM) is characterized by cerebellar herniation through the foramen magnum and potentially into the upper portion of the spinal canal [1]. Possible CM etiologies include genetic predisposition, congenital anomalies, and acquisition through trauma or illness [2]. Four types of CM (CM I, CM II, CM III, CM IV) are differentiated according to cerebellar herniation, spinal cord spacing, and severity of the disorder with most cases of CM II, III, and IV identified before birth or in early infancy [3]. CM I, however, is typically diagnosed in adulthood [4, 5] although manifestation also appears in younger populations [6]. While the exact prevalence remains unknown [6], an estimated 215,000 Americans are believed to have CM I making it the largest population of CM types [3]. CM I is a complex neurological disorder, categorized by symptomatology that often leads to debilitating headaches, neck pain, dizziness, and visual disturbances [7]. Diagnosis is made via neuroimaging techniques, specifically with the use of magnetic resonance imaging (MRI). Incidental CM I
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diagnoses are increasingly common as the use of diagnostic MRIs [8, 9] becomes more frequent, especially for children [6]. One-third to one-half of children may be asymptomatic at the time of CM I diagnosis [8], while a higher percentage of adults show symptoms (70–86 %) [10, 11]. CM I symptoms often overlap with other disorders, including fibromyalgia and chronic fatigue [12], making it difficult to distinguish CM I from other similarly manifesting disorders. Only a few studies have examined trends regarding the symptoms and diagnosis of CM I. Milhorat et al. [5] clinically examined and interviewed 364 patients with CM I between 1994 and 1997. The most frequent symptom was suboccipital headaches (81 %), and more than one-third of the group (37 %) indicated lifelong symptoms. Twentyfour percent of individuals reported the onset of symptoms due to physical trauma. The majority (59 %) of participants reported being misdiagnosed as having a mental or emotional problem. A study by Mueller and Oro [13] assessed patient-reported symptomatology of 265 patients diagnosed with CM I via MRI between 1999 and 2002. Mueller and Oro [13] found 98 % of patients presented with headache, followed by dizziness (84 %) and difficulty sleeping (72 %). In addition to headache and dizziness, the researchers report the following distinguishing CM I symptoms: neck pain and pressure, feelings of burning in the neck, exhaustion, and weakness. Since the work by Milhorat et al. [5] and Mueller and Oro [13], no sizable research has examined CM I symptomatology and diagnostic process using patient-reported data. It is important to understand and disseminate patientreported symptoms and experiences prior to and during the CM I diagnostic process to facilitate early and accurate diagnosis. Consequently, the current study contributes to the small but growing body of information of patients’ with CM I symptomatology and diagnostic experiences using the largest online patient CM registry. To better understand the complex nature and impact of CM I on patients, the United States-based Conquer Chiari Foundation and Conquer Chiari Research Center developed and implemented a voluntary online patient registry. As of April 2014, 957 unique individuals have logged onto the website and entered data pertaining to CM representing the largest national database of CM patients. The current study examines symptomatology and diagnostic information as reported in the registry by patients living with CM I.
is advertised to patients and patient caregivers via multiple methods including on the Conquer Chiari Research website. Interested individuals register with the website and complete questionnaires on multiple topics including: demographics and family background, symptoms, related conditions, treatments including pharmaceutical, surgical, and complementary alternative medicine, and impact of CM on psychosocial life areas. Participants in the registry must be diagnosed by a physician or from an MRI with a tonsillar descent of at least 5 mm. Participants must be at least 18 years of age or parents or guardians of patients under age eighteen with CM. Data included in this study were entered into the registry between August 2012 and April 2014. This work was approved by the institutional review boards of both (The University of Akron) and (Northeast Ohio Medical university). Instruments Similar to Milhorat [5] and Mueller and Oro [13], symptomatology was assessed at systems level (e.g., neurological, vestibular, visual, auditory, gastrointestinal). Participants were asked to indicate if they experienced a symptom just prior to diagnosis. More detailed information was obtained regarding the manifestations of common symptoms (pain, headache, numbness, weakness). Neurocognitive and psychological symptoms and diagnoses were also gathered. Diagnostic information included items assessing age at diagnosis, incidental versus actively sought diagnosis, time to diagnosis, specialties of physicians visited and misdiagnosis for those who actively sought a diagnosis, and reasons an MRI was performed for those diagnosed incidentally. Finally, demographic information included questions regarding age, gender, race, and associated conditions. Statistics Data were extracted from the dynamic, online patient registry database and imported into SPSS version 22 (IBM/ SPSS, Inc., Chicago, IL). Statistical analyses included descriptive statistics such as means and frequencies. For open-ended questions, qualitative data were coded into like categories.
Results Methods The current research is one component of an investigation designed to collect information from individuals with CM through the Conquer Chiari Patient Registry. The registry
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Registry participants were included in the analysis if they were diagnosed with CM I by a physician or by MRI findings and reported as a patient or the parent of a patient with CM I. This reduced the sample size of the current study from 957 to 768 registry participants.
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Clinical presentation Table 1 details patient registry demographics. Scoliosis was the most frequently reported related condition (25.39 %), followed by syringomyelia (24.05 %) and pseudotumor cerebri/intracranial hypertension (8.72 %). The most common incident to trigger onset of CM I symptoms was a car accident (5.34 %), followed by other head trauma (3.91 %), falling (2.86 %), pregnancy (2.34 %), and other events (8.07 %). Approximately 25 % of participants reported that their CM I diagnosis was found incidentally. The most commonly reported reasons for an incidental diagnosis were headache (26.55 %), receiving a CT or MRI while trying to verify another cause
Table 1 Patient information No. CM I
% CM I (n = 768)
Demographics Gender Female
630
82.03
Missing
42
12.31
Age [mean years (SD)]
35.0 (14.8)
Race White Black
670 12
87.24 1.56
American Indian
25
3.26
Alaska Native
0
0
Native Hawaiian
0
0
Other Pacific Islander
0
0
Asian
6
0.78
Other
10
1.30
Multiracial
7
0.91
Missing
38
4.95
Clinical presentation Age of onset [mean years (SD)]
20.7 (13.7)
Age at diagnosis [mean years (SD)]a
32.7 (14.5)
Knowledge of CM I prior to diagnosis
Symptomatology Just prior to diagnosis, patients with CM I reported a variety of systems affected by CM I symptoms (Table 2). Physical labor (20.42 %), changes in the weather (15.15 %), and stress (13.64 %) were reported as precipitating factors that exacerbated symptoms (data not shown; available on request). Pain was the most frequently reported symptom experienced prior to diagnosis (Table 3) with headaches the highest implicated pain type (Table 4). The most common location for headaches was at the back of the head though many participants also noted headache location behind the eyes. Multiple events were indicated as precipitating headache onset with coughing and bending over as the highest reported. Headaches (47.30 %) were most frequently reported as the worst symptom prior to diagnosis, followed by pain throughout the entire body (5.98 %) and neck and shoulder pain (4.27 %). The worst symptoms prompting patients to go to the doctor included headaches (51.38 %), syncope (4.86 %), and dizziness (4.17 %) (data not shown; available on request). Associated findings Neurocognitive and psychological comorbidities were seen in a number of patients with CM I prior to CM I diagnosis (Table 5). Approximately 44 % of participants indicated experiencing memory problems as well as aphasia prior to initial diagnosis. Depression was the most commonly reported diagnosed mood disorder (31.77 %), and almost 20 % of patients reported being diagnosed as having some type of anxiety disorder.
Yes
65
8.46
No Missing
398 305
51.82 39.71
Diagnostic experience For participants who reported that they had actively sought a diagnosis, primary care physicians/family doctors (35.83 %), neurologists (38.76 %), and neurosurgeons (43.97 %) were the most common specialties patients visited at least once during the diagnostic process (Table 6). Also for patients who reported that they had actively sought a diagnosis, average time to diagnosis was 3.43 years, as calculated from first physician visit date to diagnosis date (Table 1). There were 135 patients actively seeking diagnoses who experienced misdiagnoses. The two
Actively seeking diagnosis
307
39.97
Incidental diagnosis
191
24.87
270
35.16
Missing Time to diagnosis [mean years (SD)]b
3.43 (5.23)
a
Some dates were reported by patients in month/year only. In these cases, the patient registry database assigned the day as the first of the month. Therefore, calculated time variables (age at diagnosis, time to diagnosis) should be interpreted as ±60 days
b
for CM I symptoms (15.82 %), such as multiple sclerosis and pain in the neck, shoulders, or arms. Numbness, tingling, and burning (8.47 %) also led to incidental diagnosis as well as eye complications (6.78 %) and a variety of other unique causes (46.89 %) (data not shown; available on request).
n = 182 patients actively seeking diagnosis. Forty-nine patients were removed from the analysis due to issues with date reporting
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Neurol Sci Table 2 Symptomatology prior to diagnosis No. CM I Ear
% CM I (n = 768)
327
42.58
Fullness in ears
193
25.13
Tinnitus
261
33.98
Ear pain
159
20.70
Hearing loss
123
37.61
Sensitivity to loud noises
242
31.51
Vestibular system
351
45.70
Dizziness
275
35.81
Vertigo
200
26.04
Balance problems Nystagmus Eyes
281
36.59
122 452
15.89 58.85
Blurred vision
325
42.32
Double vision
174
22.66
Sensitivity to light
353
45.96
Strabismus
38
4.95
341
44.40
Trouble swallowing
254
33.07
Abnormal gag reflex
175
22.79
Hoarse voice
176
22.92
Gastrointestinal
226
29.43
Nausea
211
27.47
Vomiting
110
14.32
Throat
Failure to thrive (children) Trouble sleeping Sleep apnea Obstructive Central Mixed Other
12
1.56
439
57.16
77
10.03
39 21
5.08 2.73
17
2.21
503
65.49
Abnormal sweating
197
25.65
Inability to regulate temperature
273
35.55
Bladder problems
242
31.51
Bowel problems
220
28.65
Fainting/blackouts
180
23.44
Fatigue
454
59.11
Shortness of breath
266
34.64
most common types of misdiagnoses were psychological and neurological disorders (Table 7). The most common emotion experienced during the time of diagnosis was fear (42.19 %) followed by a sense of being overwhelmed (40.23 %), shock (38.08 %), relief (35.16 %), resolve (24.61 %), sadness (21.09 %), and anger (16.05 %) with resignation being the least reported (4.30 %). Some patients noted frustration at the delay in diagnosis, as exemplified by the participant comment: ‘‘Why so many years to find this?’’ Interestingly, only
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8.46 % of patients indicated that they had previously heard of CM I or knew anyone with the condition.
Discussion CM is a complex disorder with an etiology that is not yet fully understood. Comparable to the work by Milhorat [5], the current research presents the patient-reported events that triggered CM I symptoms. Similar rates of women report pregnancy as a triggering symptom onset in the work by Milhorat [5] and the current research (2.4 and 2.3 %, respectively). Consequently, pregnancy may be a concern for some women already diagnosed with CM I. However, Mueller and Oro [14] report that, among seven pregnant women diagnosed with CM I either prior to or at the time of pregnancy, none displayed significant increases in symptoms during or after delivery. Another similarity between the work of Milhorat [5] and the current study regarding symptom onset is the reporting of trauma as a symptom-triggering incident. The current study found that trauma from car accident (5.3 %), other head trauma (3.9 %), and falls (2.7 %) were the most commonly reported trauma-related triggering factors. Milhorat [5] reported that 18.3 % of patients indicated whiplash and direct hits to the neck and head as a trigger for symptom onset. A chart review by Wan et al. [15] on 85 patients revealed that 12.9 % of patients sustained minor head or neck trauma prior to symptom onset. When stricter inclusion criteria were used to determine whether trauma was truly a causal factor for symptom onset, the number of cases with traumaattributable onset was reduced to 3.5 %. This finding suggests a discrepancy between the self-reported work by Milhorat et al. [5] and the current research with that of the chart review methodology used by Wan et al. [15]. However, direct comparisons between the results of the current research and those of Milhorat et al. [5] to the work of Wan et al. [15] are difficult as neither Milhorat nor the current research assessed the severity of the trauma. Further, the self-report nature of the work by Milhorat et al. [5] and the current research limits the ability to identify the exact precipitating factors for symptom onset. Recent research has also attempted to understand the natural history of CM I by exploring symptomatology and associated neuroanatomical manifestations. Symptomatology is variable, causing otoneurological, optical, respiratory, psychological, and cognitive effects [1, 3–5, 7, 9, 16, 17]. Prior work has demonstrated that the most common symptom of CM I is a suboccipital headache exacerbated by physical exertion [5, 13]. Likewise, in this study the most common symptom was a headache located in the back of the head with exercise and physical labor commonly reported as the precipitating event. Another
Neurol Sci Table 3 Pain, weakness, and numbness localization prior to diagnosis No. CM I Pain (pain and headaches combined)
% CM I (n = 768)
589
76.69
Headaches
564
73.44
Neck Shoulders
472 394
61.46 51.30
Upper back
254
33.07
Middle back
161
20.96
Lower back
274
35.68
Arms
229
29.82
Hands
205
26.69
Legs
222
28.91
Feet
172
22.40
452
58.85
Right arm
246
32.03
Right hand
322
41.93
Right leg
150
19.53
Right foot
207
26.95
Left arm
252
32.81
Left hand Left leg
300 173
39.06 22.53
Left foot
218
28.39
Weakness
405
52.73
right arm
238
30.99
Right hand
238
30.99
Right leg
171
22.27
Right foot
111
14.45
Left arm
250
32.55
Left hand
236
30.73
Left leg
196
25.52
Left foot
122
15.89
Numbness/tingling
similarity to previous work [5, 13] was the frequently reported symptom of ocular disturbances with common examples being sensitivity to light, blurred vision, and double vision. Consistent with the work by Mueller and Oro [13], the current research found that the patients experienced multiple neurocognitive and psychological comorbidities. Depression, anxiety, and problems with decision making are important elements for healthcare providers to consider in their delivery of medical care and advice [18]. For example, headache, one of the most frequently reported symptoms in this survey, causes disruptions that decrease quality of life [19, 20]. The more quickly and accurately a patient receives diagnosis and treatment, the better he or she can manage symptoms and return to a normal lifestyle [19]. The overlapping of CM I symptoms with those of other disorders complicates differential diagnosis. One such
symptom is headache. Currently, there are no criteria specific to a headache that is attributable to CM I [21]. Furthermore, it has not been suggested that CM I induces headache [22]. Clinicians should be encouraged to perform comprehensive physical, neurological, and mental status examinations, as well as evaluation of non-clinical factors to correctly determine the cause of headache [21]. CM I could also be mistaken for other disorders, even if tonsillar descent has been discovered on an MRI [22]. Two examples are intracranial hypotension (pseudo-Chiari) and intracranial hypertension secondary to hydrocephalus [22]. Patients with these conditions present symptoms congruent with CM I. Further, CM I can complicate the differential diagnosis of postdural puncture headache at parturition [23]. This is because CM I symptoms frequently begin at child-bearing age or CM I can be acquired from administration of neuraxial anesthesia [23]. Similar to the results reported by Milhorat et al. [5], the current research reveals that frequent misdiagnoses were psychological and neurological in origin with the most common being depression, stress/anxiety, multiple sclerosis, and psychogenic issues. Patient experience during the search for correct diagnosis of CM I mirrors that of individuals suffering from rare disease [24]. In the current research, patients experienced diagnostic delay, lack of prior knowledge about CM I, and a variety of misdiagnoses. Diagnosis is further complicated by the lack of agreement as to what constitutes CM I [25]. There are discrepancies in scientific literature as to what neural and/or other structural abnormalities define this disorder. CM I is conventionally defined as a downward descent of the cerebellar tonsils of at least 5 mm below the foramen magnum [3]. However, other sources state that this descent can be as small as 3 mm [16]. Additionally, it has been stated that tonsillar descent of greater than 12 mm is associated with the presence of CM I symptoms and that, while nearly 1 % of adults may have radiographic evidence of a tonsillar descent greater than 5 mm, only 0.01–0.04 % of those with this evidence actually manifest symptoms indicative of CM I [2]. Because the information from this survey was gained through selfreport, we do not have information about what specific criteria physicians used to diagnose the CM I in these participants. Delay in CM I diagnosis can have serious implications with diagnosis later in life related to an increased risk for severe headache syndrome, neck pain, vertigo, or ataxia [6]. It is recommended that patients who have CM I presenting with progressive or intractable symptoms and/or expanding syringomyelia receive surgery as soon as possible in order to prevent further surgical deterioration [2]. Proper surgical intervention may result in complete decompression of the medulla oblongata, improving clinical symptoms [17]. Over one-third of the patients in this
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Neurol Sci Table 4 Headaches and precipitating headache onset as a pain subset No. CM I
% CM I (n = 768)
564
73.44
Back of the head
386
50.26
Top of the head
101
Headache
Right side of the head Left side of the head Front of the head
Table 5 Neurocognitive diagnosis
and
psychological
findings
% CMI (n = 768)
Memory problems
337
43.88
13.15
Aphasia
336
43.75
13.67
Problems with decision making
243
31.64
89
11.59
Problems planning
224
29.17
151
19.66
Personality disorder
15
1.95
34
4.43
105
Behind the eyes
206
26.82
Deep inside the head
115
14.97
All over
181
23.57
Learning disorder Mood disorder
54 267
7.03 34.77
Depression
244
31.77
1
0.13
12
1.56
Headache precipitating event Coughing Sneezing
362 311
Laughing
47.14 40.49
Adjustment disorder Bipolar disorder
262
34.11
Mood disorder NOS
4
0.52
Singing
94
12.24
Anger
1
0.13
Talking
75
9.77
Major depressive disorder
3
0.39
2
0.26
Bending over
361
47.01
PMS
Change in position
247
32.16
Anxiety disorders
153
19.92
79
10.29 2.21
Exercise
315
41.02
Anxiety
Desk work
125
16.28
PTSD
17
40.89
GAD
20
2.60
5
0.65
3
0.39
2 21
0.26 2.73
314
Sexual activity
123
16.02
Social anxiety
Nothing specific
154
20.05
ADHD
13.41
Agoraphobia Panic attacks/disorder
Other
103
registry who actively pursued a diagnosis saw at least one primary care provider. Findings have indicated that the usage of an MRI for patients experiencing headache is costly and typically yields little significant, clinical results [20]. This lack of utility may lead to few primary care physician referrals to imaging services which could provide the CM I diagnosis. There are several factors that can influence referral to imaging services when the chief complaint is a headache [26]. Some of these factors include access to resources, training of medical staff, and disparities due to patient demographics [26]. Patient and physician education about CM I will help improve the diagnosis timeline, potentially reduce misdiagnoses, and allow for early intervention to prevent further deterioration and needless patient suffering. The voluntary, self-reporting nature of the registry yielded unique insight into CM I. Although the results of the current research replicate many of the findings regarding CM I clinical presentation, symptomatology, and diagnosis [5], data were self-reported and therefore subjective. In addition, the web-based nature of the registry may have limited the generalizability of the current research. Minorities, individuals in rural areas, and women are less likely to have home computers and internet access [27] and may have been underrepresented in the registry. Our study
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to
No. CM I
Obsessive compulsive disorder
Physical labor
prior
included a large sample of women (82.03 %) which is similar to other CM I studies that have used samples with predominantly female patients [5, 28, 29]. Minorities, however, were significantly underrepresented compared to the expansive Caucasian sample (87.24 %). It is impossible to know if minority representation is reflective of those affected with CM I due to underrepresentation of minorities in research [30, 31] and the lack of including race and ethnicity within demographic information in previous CM I studies [for example, 5, 28, 29]. In addition, findings have shown that primary care physicians who treat African American patients have more difficulty accessing diagnostic imaging services and medical specialists of high quality in comparison to those physicians who treat Caucasian patients [32]. The challenges with diagnosis and treatment faced by African Americans patients may be reflected in their underrepresentation in the current research.
Conclusion Using a large sample of 768 registry participants, the current study adds to the existing literature by providing patient-reported CMI I symptomatology and clinical
Neurol Sci Table 6 Frequency of CM I patients who saw specialty at least once during diagnostic process Specialty
No. CM I
% CMI (n = 307a)
Ear/nose/throat
22
7.17
Endocrinologist
4
1.30
Gastro intestinal specialist Neuro-ophthalmologist
5 5
1.63 1.63
Neurologist
119
38.76
Neurosurgeon
135
43.97
5
1.63
Ophthalmologist
10
3.26
Orthopedic surgeon
14
4.56
Obstetrician/gynecologist
Pain specialist
14
4.56
Pediatric neurologist
17
5.54
Pediatric neurosurgeon
23
7.49
Pediatrician
15
4.89
Physiatrist
3
0.98
110
35.83
Psychiatrist
4
1.30
Psychologist
1
0.33
17
5.54
44
14.33
Primary care physician/family doctor
Rheumatologist Otherb a
Patients actively seeking diagnosis
Table 7 Patient-reported misdiagnoses No. CM I
% CMI (n = 135a)
Psychologicalb
26
19.26
Neurologicalc
26
19.26
Chronic fatigue syndrome
16
11.85
d
Autoimmune
15
11.11
Spinal abnormalitye
8
5.93
Musculoskeletalf
8
5.93
Respiratoryg
5
3.70
Cardiovascularh
5
3.70
Vestibulari
4
2.96
Sinus
4
2.96
Visualj Infectionk
3 2
2.22 1.48
Overweight
2
1.48
Pseudotumor
2
1.48
Misappropriated pain
2
1.48
Inflammation
1
0.74
Thyroid disorder
1
0.74
Anemia
1
0.74
Vitamin D deficiency
1
0.74
l
Normal
1
0.74
Reflux
1
0.74
Allergies
1
0.74
b
Patients reported the following other specialties: Cardiologist, chiropractor, ER doctor, pulmonologist, sleep doctor, asthma and allergy doctor, general practitioner, internal medicine, DO, urologist, physician assistant, referral specialist doctor, pediatric orthopedic surgeon, urgent care doctor, hematologist, hand specialist, nurse practitioner, radiologist, spine specialist, stroke/TIA, hernia specialist, sports chiropractic, orthopedist, infectious disease doctor, geneticist, cerebrovascular disease, speech therapist
a
135 patients actively seeking a diagnosis who reported experiencing a misdiagnosis
b
Psychogenic (3), bipolar (1), depression (10), stress/anxiety (12)
c
Cerebral palsy (2), MS (5), myasthenia gravis (1), non-specific brain change (1), concussion (1), essential tremor (1), headache/migraine (15)
d
Lupus (5), other (10) Bulging/herniated disk (3), spondylosis (1), degenerated/slipped disk (1), spinal misalignment (1), craniocervical syndrome (1), tethered cord (1)
e
presentation. Despite advancements in understanding disease process, origin, and symptomatology in the past 15 years [2, 16, 33, 34], patients continue to experience delays in diagnosis as well as misdiagnoses. The current research sheds light on some of these diagnostic experiences. One-third of patients saw at least one primary care physician during the search for the diagnosis. Most patients were diagnosed with a disorder of which they had no prior knowledge, experienced a myriad of emotions upon diagnosis, and many had comorbid psychological diagnoses that may have complicated the CM I diagnostic and management process. Further research is needed to determine the impact of the patient–physician relationship throughout the disease time course as well as the effectiveness of various specialties in the diagnosis and management of CM I as a whole. Patient and physician education about CM I
f
Facet syndrome (1), muscle strain (2), osteopenia (1), sesamoiditis (1), ‘‘stress walk’’ (1), fibromyalgia (2)
g
Stridor (1), laryngomalacia (1), epiglottis malacia (1), breathholding spells (1), sleep apnea (1)
h
TIA (2), vasodepressive presyncope (1), pericardial effusion (1), hypertension (1)
i
BPPV (1), Meniere’s disease (2), vestibular neuritis (1)
j
Strabismus (1), papilledema (1), poor vision (1)
k
Syphilis (1), meningitis (1)
l
Residual pain from accident (1), reflex sympathetic dystrophy (1)
may help reduce diagnosis delay, allowing for early intervention and the prevention of further deterioration and needless patient suffering.
123
Neurol Sci Acknowledgments We wish to thank the patients and caregivers of patients with CM who provided information on the registry. We also wish to thank the Conquer Chiari Foundation and especially Rick Labuda who designed the patient registry and recruited patient participants. Without his efforts, this research would not be possible.
14.
15. Conflict of interest of interest.
The authors declare that they have no conflict 16.
Ethical standard All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
17.
18. Informed consent Informed consent was obtained from all individual participants included in the study. 19.
References 1. National Institute of Neurological Disorders and Stoke. Chiari malformation fact sheet. http://www.ninds.nih.gov/disorders/ chiari/detail_chiari.htm. Accessed 1 June 2014 2. Heiss J (2013) Epidemiology of the Chiari I malformation. In: Tubbs RS, Oakes WJ (eds) The Chiari malformations. Springer Science ? Business Media, New York, pp 83–92 3. Speer MC, Enterline DS, Mehltretter L, Hammock P, Joseph J, Dickerson M et al (2014) Chiari type i malformation with or without syringomyelia: prevalence and genetics. J Genet Couns 12(4):297–311 4. Dyste GN, Menezes AH, VanGilder JC (1989) Symptomatic Chiari malformations. An analysis of presentation, management, and long-term outcome. J Neurosurg 71(2):159–168 5. Milhorat TH, Chou MW, Trinidad EM, Kula RW, Mandell M, Wolpert C et al (1999) Chiari I malformation redefined: clinical and radiographic findings for 364 symptomatic patients. Neurosurgery 44(5):1005–1017 6. Aitken LA, Lindan CE, Sidney S, Gupta N, Barkovich AJ, Sorel M et al (2009) Chiari type I malformation in a pediatric population. Pediatr Neurol 40(6):449–454 7. Fernandez AA, Guerrero AI, Martinez MI, Vazquez ME, Fernandez JB, Octavio CI et al (2009) Malformations of the craniocervical junction (Chiari type I and syringomyelia: classification, diagnosis and treatment). BMC Musculoskelet Disord 10(Suppl 1):S1–S11 8. Wu YW, Chin CT, Chan KM, Barkovich AJ, Ferriero DM (1999) Pediatric Chiari I malformations: do clinical and radiologic features correlate? Neurology 53(6):1271–1276 9. Genitori L, Peretta P, Nurisso C, Macinante L, Mussa F (2000) Chiari type I anomalies in children and adolescents: minimally invasive management in a series of 53 cases. Childs Nerv Syst 16(10–11):707–718 10. Meadows J, Kraut M, Guarnieri M, Haroun RI, Carson BS (2000) Asymptomatic Chiari type I malformations identified on magnetic resonance imaging. J Neurosurg 92(6):920–926 11. Elster AD, Chen MY (1992) Chiari I malformations: clinical and radiologic reappraisal. Radiology 183(2):347–353 12. Ellenbogen R, Bauer D (2013) Association between fibromyalgia, chronic fatigue, and the Chiari I malformation. In: Tubbs RS, Oakes WJ (eds) The Chiari malformations. Springer Science ? Business Media, New York, pp 265–271 13. Mueller DM, Oro JJ (2004) Prospective analysis of presenting symptoms among 265 patients with radiographic evidence of
123
20.
21.
22.
23.
24. 25. 26.
27. 28. 29.
30. 31.
32.
33.
34.
Chiari malformation type I with or without syringomyelia. J Am Acad Nurse Pract 6(3):134–138 Mueller DM, Oro JJ (2005) Chiari I malformation with or without syringomyelia and pregnancy: case studies and review of the literature. J Am Perinatol 22(2):67–70 Wan MJ, Nomura H, Tator CH (2008) Conversion to symptomatic Chiari I malformation after minor head or neck trauma. Neurosurgery 63:748–753 Schijman E (2004) History, anatomic forms, and pathogenesis of Chiari I malformations. Childs Nerv Syst 20(5):323–328 Zhang ZQ, Chen YQ, Chen YA, Wu X, Wang YB, Li XG (2007) Chiari I malformation associated with syringomyelia: a retrospective study of 316 surgically treated patients. Spinal Cord 46(5):358–363 Martin LR, Williams SL, Haskard KB, Dimatteo MR (2005) The challenge of patient adherence. Ther Clin Risk Manag 1(3):189–199 Ryan RE Jr, Pearlman SH (2004) Common headache misdiagnoses. Prim Care Clin Office Pract 31(2):395–405 Jordan JE, Ramirez GF, Bradley WG, Chen DY, Lightfoote JB, Song A (2000) Economic and outcomes assessment of magnetic resonance imaging in the evaluation of headache. J Natl Med Assoc 92(12):573–578 Grazzi L, Andrasik F (2012) Headaches and Arnold-Chiari syndrome: when to suspect and how to investigate. Curr Pain Headache Rep 16(4):350–353 Mea E, Chiapparini L, Leone M, Franzini A, Messina G, Bussone G (2011) Chronic daily headache in the adults: differential diagnosis between symptomatic Chiari I malformation and spontaneous intracranial hypotension. Neurol Sci 32(Suppl 3):S291– S294 Brown JP, Lea DE, Douglas MJ (2013) Acquired Chiari I malformation: a differential diagnosis in severe postdural puncture headache? Int J Obstet Anesth 22(1):81–83 Kole A, Faurisson F (2010) Rare diseases social epidemiology: analysis of inequalities. Adv Exp Med Biol 686:223–250 Proctor MR, Scott RM, Oakes WJ, Muraszko KM (2011) Chiari malformation. Neurosurg Focus 31(3) Introduction Couchman GR, Forjuoh SN, Rajab MH, Phillips CD, Yu J (2004) Nonclinical factors associated with primary care physicians’ ordering patterns of magnetic resonance imaging/computed tomography for headache. Acad Radiol 11(7):735–740 Wilson K, Reiser K (2003) Social stratification and the digital divide. Soc Sci Comp Rev 21:133–143 Lewis AR, Kline LB, Sharpe JA (1996) Acquired esotropia due to Arnold-Chiari I malformation. J Neuroophthalmol 16(1):49–54 Kaplan Y, Oksuz E (2008) Chronic migraine associated with the Chiari type 1 malformation. Clin Neurol Neurosurg 110(8):818–822 Svensson CK (1989) Representation of American blacks in clinical trials of new drugs. JAMA 261(2):263–265 Hussain-Gambles M, Atkin K, Leese B (2004) Why ethnic minority groups are under-represented in clinical trials: a review of the literature. Health Soc Care Community 12(5):382–388 Bach PB, Pham HH, Schrag D, Tate RC, Hargraves JL (2004) Primary care physicians who treat blacks and whites. N Engl J Med 351(6):575–584 Christophe C, Dan B (1999) Magnetic resonance imaging cranial and cerebral dimensions: is there a relationship with Chiari I malformation? A preliminary report in children. Eur J Paediatr Neurol 3(1):15–23 Tubbs RS, McGirt MJ, Oakes WJ (2003) Surgical experience in 130 pediatric patients with Chiari I malformations. J Neurosurg 99(2):291–296
