To the Editor: New-onset headache within a week after craniotomy is commonly recognized
as acute post-craniotomy headache (PCH). This headache pain mainly occurs within the
first few post-operative days and is remarkably associated with a younger age, the
female sex, and the retrosigmoid approach.[1] The mechanisms of PCH mainly involve
mechanical and chemical irritation and aseptic inflammation of the scalp muscles,
periosteum of the skull, dura mater, and trigeminal nerves.[2] The frequent onset
of PCH leads to impaired daily activities, decreased quality of life, prolonged post-operative
recovery, and worsened social functioning. The differential diagnosis of acute PCH
may also lead to the patient receiving many unnecessary tests, including invasive
tests such as a lumbar puncture.
Cervicogenic headache (CEH) is defined as a headache attributed to disorders of the
cervical spine and its component bony, disc, and/or soft tissue elements, with or
without accompanying neck pain.[3] An earlier review documented that 3 of 95 patients
who had undergone acoustic neuroma surgery developed CEH-like PCH.[4] The International
Classification of Headache Disorders (ICHD)-3 criteria classify such disorders as
a CEH caused by inappropriate positioning during the operation and should be precisely
differentiated from PCH. The elimination of cervical pain sources remains a crucial
component of the treatment of CEH, which is not included in the usual management of
PCH. Undifferentiated CEH results in neglected management of cervical pain sources
and risks of extensive analgesic consumption. However, exhaustive characteristics
of CEH following acoustic neuroma resection and other craniotomies have yet to be
disclosed. In this prospective study, we investigated the incidence, clinical manifestations,
and risk factors of CEH following craniotomy.
This monocentric, prospective, observational study was designed based on an ongoing
institutional PAINFREE program (2020–2023), which was proposed to improve post-craniotomy
analgesia. The program protocol was reviewed and approved by the Institutional Ethical
Review Board (Approval No. KY2020-008-02-1) of Beijing Tiantan Hospital. Consecutive
patients admitted for elective craniotomy were screened. Those who signed the inform
consent and agreed to participate in the study process were enrolled in the PAINFREE
program. Participants who entered the program were asked about their overall post-operative
pain symptoms by the program assistants until discharge. Subjects with positive compliance
were therefore screened and interviewed by pain management specialists through consultations.
Through the program, participants’ demographic, sociodemographic, admissive, peri-operative,
and consultative data and information were collected and recorded by the program assistants
and pain management specialists. Between Januaury 2020 and May 2022, consecutive adult
patients enrolled in the PAINLESS program were included in the current study. Participants
who developed life-threatening peri-operative complications, were admitted to the
intensive care unit, or were uncooperative with the consultation inquiries or management
plans were excluded.
Eligible participants were allocated to two groups based on whether new-onset CEH
was diagnosed after craniotomy. Patients with suspected clinical manifestations were
evaluated for CEH using the revised Cervicogenic Headache International Study Group
and ICHD-3 criteria.[3,5] Manual therapy was denied for peri-operative safety considerations.
Diagnosed patients were administered oral analgesics. Diagnostic nerve blockade (DNB)
was applied if the headache pain was extremely severe or drug-resistant for both diagnostic
and therapeutic purposes. The DNB was accomplished using individually formulated mixtures
of 2% lidocaine or 1% ropivacaine and normal saline. Those who obtained a positive
DNB were therefore confirmed to have a CEH. Other clinically suspected patients who
showed little responsiveness to the DNB were diagnosed with headache following craniotomy
attributed to extensive origination.
Data acquisition was completed by two of our program assistants. Patients’ demographic
information (age, sex, and body mass index [BMI]), sociodemographic information (history
of smoking and alcohol drinking), pre-existing comorbidities (history of cervicospinal
disorder, chronic headache, psychiatric disorder, and systemic diseases), and peri-operative
data (craniotomy etiology, surgical approach, incision length, operation duration,
operating positioning, and anesthesia technique) were extracted from the PAINLESS
case report forms. Information and data were obtained during the consultation (primary
consultative diagnosis and its approaches, responsiveness to management approaches
determined during the consultation, headache pain onset time, laterality, property,
intensity [documented as 0 to 10 points on a numerical rating scale, in which 0 represented
for no pain and ten denoted the greatest pain imaginable, and pain scores of 0 to
3 points denoted mild pain, 4 to 7 points denoted moderate pain, and 8 to 10 points
denoted severe pain], provocation, and accompanying symptoms) using the PAINLESS case
report form and the institutional case record system. Subjects were deidentified after
the data acquisition and interpretation were completed according to the PAINLESS program
protocol.
The statistical analysis was performed using R Studio software (RStudio v. 2021.09.0
+ 351 “Ghost Orchid”; R Core Team, Vienna, Austria) and associated packages. Descriptive
data are presented as the means ± standard deviations or median (interquartile range
[IQR]) for continuous variables and n (percentages) for categorical variables. Univariate
comparisons between two arms were performed using the chi-squared test or Fisher's
exact test for categorical variables. Continuous variables were compared using Student's
t test or the Wilcoxon rank sum test. We performed univariate and multivariate logistic
regression analyses with CEH as a binary outcome variable to assess the associations
with demographic, clinical, and peri-operative variables. The magnitude of the association
with the clinical outcome was reported as the odds ratio (OR) (95% confidence interval
[CI]). All tests were two-sided. A P value <0.05 was set to be statistically significant.
During the study period, 1629 consecutive patients cumulatively underwent elective
craniotomy in the study setting [Supplementary Figure 1]. Two hundred patients were
excluded based on the exclusion criteria (20 due to severe peri-operative complications,
157 due to intensive care unit admission, and 23 due to a lack of cooperation with
the consultation or DNB), resulting in a total of 1429 patients enrolled in this prospective
study. The mean age was 48.98 ± 13.40 years, and 53.4% (763/1429) were women. Headache
following craniotomy was reported in 53.3% (761/1429) subjects, among whom 83 were
clinically diagnosed with CEH through consultations. Conservative treatments were
initially applied, and positive pain relief was obtained in 61.4% (51/83) patients.
DNB was used as needed in the other 38.6% (32/83) individuals, among whom 96.9% (31/32)
acquired immediate headache pain relief and were confirmed to have a CEH. One patient
presented with a CEH that failed the anesthetic blockade. Further mental examinations
indicated that this patient was under significant stress, and the diagnosis of CEH
was denied. In summary, 82 patients were finally diagnosed with CEH based on clinical
manifestations and interventional techniques. The incidence was 5.8% (82/1429). The
incidence of pre-existing chronic headache (medical history, not a new-onset or acute
exacerbation) was 9.8% (8/82) in the CEH population and 12.2% (165/1347) among participants
without CEH. The between-group difference was 0.603 according to the Chi-squared test.
Patients with CEH more frequently had a history of cervicospinal disorders (72.0%
[59/82] vs. 19.5% [263/1347], P < 0.001), and the difference between groups was statistically
significant. No differences were detected in age, sex, BMI, smoking, intemperance,
and other pre-existing medical history. Among the peri-operative data and information,
patients with CEH had longer operation time (6.45 [IQR: 5.43–7.38] hours vs. 5.10
[IQR: 4.60–5.70] hours, P < 0.001). Other data involving the craniotomy etiology,
surgical approach, incision length, operation positioning, and anesthesia technique
did not differ between patients with or without CEH following craniotomy [Supplementary
Table 1].
Generally, CEH was present 6.0 [IQR: 5.0–8.0] days post-operatively. Headache pain
was primarily described as unilateral (71/82, 86.6%), moderate to severe (65/82, 79.3%),
dull (54/82, 65.9%), or drilling (21/82, 25.6%) headache pain. Headache was mostly
provoked by neck movement or pressing (68/82, 82.9%). Reduced neck motion was reported
in 93.9% (77/82) of patients. Nausea with or without vomiting was reported by 31.7%
(26/82) of patients. In addition, concurrent neck pain, photophobia, and phonophobia
were reported in 29.3% (24/82), 13.4% (11/82), and 6.1% (5/82) of patients, respectively
[Supplementary Table 2]. All collected demographic, sociomedical, and peri-operative
data and information were entered into the univariate logistic analyses. Continuous
variables such as age, BMI, incision lengths, and operation duration were categorically
transformed during the process. A history of cervicospinal disorders (OR: 10.57 [95%
CI: 7.01–16.29], P < 0.001) and an operative duration >5 h (OR: 4.95 [95% CI: 2.91–9.07],
P < 0.001) were suggestive of CEH following craniotomy. In multivariate analyses,
the association remained statistically significant; a history of cervicospinal disorders
(OR: 10.84 [95% CI: 7.15–16.80], P < 0.001) and an operation duration >5 h (OR: 5.18,
[95% CI: 3.01–9.60], P < 0.001) were positively associated with the development of
CEH following craniotomy [Supplementary Table 3].
In the study, we identified a set of characteristics and several variables associated
with CEH following craniotomy. Pre-existing cervicospinal disorders and prolonged
operation durations >5 h were associated with an increased risk of developing CEH
following craniotomy. Previous studies demonstrated the incidence of CEH was 4.1%
(75/1838) of the general population.[6] In our study, 5.74% (82/1429) of the included
patients developed CEH after craniotomy, which was similar to and slightly higher
than those of a previous investigation, in which the occurrence of CEH similar to
PCH was 3.2%.[4] Regarding the onset time, CEH developed on the 6th (IQR: 5–8th) post-operative
day, which is the late onset and did not match empirical recognition. We speculate
that the late onset is due to the early post-operative administration of systemic
corticosteroids the following neurosurgery. CEH is characterized by moderate to severe
headaches in the occipitofrontal region that may be precipitated by head movement.
The pain presents as uni/bilateral, not throbbing or lancinating in nature, with fluctuating
severity in non-clustering episodes and variable duration, and is sometimes accompanied
by ipsilateral neck, shoulder, or arm pain. Our results were consistent with the aforementioned
findings. More than one-quarter of the CEH population failed to determine the characteristics
of their headache. The authors proposed that concurrent post-craniotomy pain may interfere
with CEH pain and lead to an ambiguous headache pain configuration. Provocative factors
were found in 86.6% (71/82) of participants in the study. The most typical trigger
was neck movement or pressing, which generated headaches in >80% (68/82) of participants.
Other accompanying mechanical or autonomic symptoms reported in the current study
were also consistent with previous investigations.[6,7]
Our study had limitations. Due to the observational nature, we failed to collect extensive
imaging data. For the same reason, comparisons among CEH following craniotomy, acute
PCH, post-craniotomy pain, and headache following craniotomy attributed to other causes
were beyond our estimation. Additionally, data from the excluded participants were
not included in our estimation in this analysis. These results warrant further studies.
In summary, CEH is an uncommon post-operative complication of elective craniotomy.
Operations longer than 5 hours and pre-existing cervicospinal disorders were significantly
associated with the development of CEH following craniotomy. We proposed that the
findings would enable pain physicians and neurosurgeons to recognize CEH following
craniotomy. As CEH and PCH may overlap within the first week post-operatively, the
ICHD-3 criteria might be subjective. Our results should be carefully considered.
Conflicts of interest
None.
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