Abstract

The presence of air inside the cranial cavity is called pneumocephalus (PNC). It is commonly caused by trauma but can also be a result of surgical procedures and other factors. This systematic review aims to discuss the case reports on PNC after spinal surgery, published in PubMed/Medline, Embase, Scopus, and Web of Science up to July 2023. Built-up precise audit strategies were utilized for screening and information extraction. Of 428 studies, thirty-six reports from 14 countries, comprising 37 patients, were included. We found out the most common symptoms in patients with PNC, in order of prevalence, were headache (up to 59% of patients), nausea, dizziness, and seizures. In 62% of the cases, a dural tear was clearly quoted. Additionally, in the studies that reported the time interval between surgery and clinical presentation of PNC, a large majority of patients displayed PNC after 24 hours (55%). The most used diagnostic method and treatment modality in our studies were computerized tomography (CT) scan (81%) and conservative treatment (70%), respectively. We propose that every patient who underwent spinal surgery, when they complained of a newly onset headache, especially after 24 hours of the operation, a brain CT scan to rule out the presence of PNC is beneficial

Keywords:Pneumocephalus; Spinal Surgery; PNC; Systematic Review

Introduction

Pneumocephalus (PNC) is a rare condition characterized by the accumulation of gas or air in the cranial cavity. It is typically caused by specific factors such as head trauma or cranial surgeries [1-3]. Other common causes include intracranial neoplasms, infections, neurosurgical or otolaryngological procedures, and diagnostic interventions [2,4,5]. Several factors, including anesthesia type, head position, surgery duration, and the presence of hydrocephalus, can influence the development of PNC [6,7]. While dural injury and invasive spinal procedures can contribute to PNC, they are less frequently observed in such cases [1,7]. Although PNC after spinal surgery is a rare phenomenon, if it occurs, it can cause multiple complications, including difficulty in awakening from anesthesia, the occurrence of tonic-clonic seizures, or even the induction of status epilepticus, possibly due to the significant amount of gas inside the cranium [8]. PNC is also regarded by its severity as simple and tension, ensuring proper treatment [6,7].

Simple PNC typically resolves spontaneously without significant complications, whereas tension PNC requires immediate medical attention due to symptoms of increased intracranial pressure [6,7,9]. Usually, there are three methods for the diagnosis of PNC. Although plain skull radiography can be used, it is generally considered unreliable in comparison with Computed Tomography (CT) scanning and Magnetic Resonance Imaging (MRI) [5,10,11]. From the therapeutic point of view, most cases of PNC are treated conservatively with bed rest, raising the head of the bed by 30, oxygen therapy, antipyretics, painkillers, and osmotic diuretics. Tension PNC is an exception and considered a neurosurgical emergency that usually needs immediate intracranial decompression through a variety of surgical interventions [5,10]. There is currently no consensus among experts on evidence-based guidelines for managing PNC in neurosurgery. Given the lack of systematic reviews specifically focusing on postoperative PNC after spinal surgery, conducting such a review would be highly valuable. It would provide a more accurate understanding of the complications and disadvantages associated with PNC after spine surgery and assess the quality of existing reports. This information could greatly assist in making clinical decisions when faced with such incidents. While large cohort studies and randomized controlled trials offer important statistical insights, they often fail to capture the in-depth clinical details needed to understand rare or atypical symptoms. In contrast, case reports and case series provide comprehensive clinical observations. Given the rarity of this condition, extensive studies have not been conducted on this topic. This systematic review evaluated PNC after spine surgeries (in terms of presentation, diagnosis, and treatment) to provide an appropriate guideline for the correct management of this rare occurrence.

Materials and Methods

This systematic review was reported following the guidelines and checklist of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [12] and registered in the International Prospective Register of Systematic Reviews; PROSPERO (CRD42023467213, https://www.crd.york.ac.uk/PROSPERO/). Search strategy: We searched the databases of PubMed, Embase, Scopus, and Web of Science up to July, 2023 using the following Mesh keywords which were combined first with “OR” then by “AND”: “Spine Surgery,” “Laminectomy,” “Spinal Decompression,” “Discectomy”, “Kyphoplasty”, “Vertebroplasty”, “Foraminotomy”, “Spinal Fusion”, “Herniated Disc Surgery”, “Spinal Operation”, “Scoliosis Surgery”, and “Pneumocephalus”, “Pneumatocele”, “Intracranial Aerocele”, and “Pneumoventricle”. Studies were considered eligible for inclusion in this systematic review if they had the following PICOS conditions: Population (P) and Intervention (I) for the patients undergoing spinal surgery, Comparison (C) for comparing the simple with the tension PNC, Outcomes (O) of the event, and Study design (S) stands for only case series and case reports. We excluded those studies that failed to report the outcome, had non-English language abstracts, and were unavailability in full text (Figure 1). Study Selection: In the initial step, any duplicate entries were eliminated. Subsequently, two reviewers (S.A.G. and A.O.K.) independently inspected references in two consecutive phases. At the first stage, reviewers appraised titles and abstracts and apart those that did not meet inclusion criteria or were not accessible but kept abstracts with inadequate information for full-text evaluation. Then, reviewers independently evaluated full-text articles and omitted those not meeting eligibility criteria or those that were inaccessible. Any incongruities between two independent reviewers were resolved by debate with a senior reviewer (F.O.K).

Risk of Bias Assessment

Bias in case report studies is unavoidable. In any case, standardized tools have been created to evaluate their methodological quality in systematic reviews. Subsequently, two Authors (Mah.S., Mas.S.) independently evaluated study quality employing a standard tool provided by the Joanna Briggs Institute (JBI) [13]. The JBI risk-of-bias assessment tool for case reports consists of eight questions that assess the presence or absence of various reported items. The possible answers to these items include yes, no, unclear, and not applicable. If each item was clearly depicted, it was evaluated as “Yes,” “No” if it was not presented, “Unclear” if it was not clear, and “Not applicable” in case it did not seem to be applied. The result of the risk of bias assessment using the JBI checklist was reported as a checklist instead of a cumulative score.

Data extraction

Two authors (Mah.S. and A.O.K.) independently extricated the following data: first author, publication date, sample size, patients’ characteristics (age and sex), surgery, sign and symptom, type of PNC, time until developing PNC, treatment, outcome, and design of each study. A third author (F.O.K.) interceded when the two authors opposed.

Aims & Objective

i. To decrease spasticity and prevent contractures and deformities from occurring.
ii. The aim is to enhance gross motor function to achieve maximum independence.
iii. To enhance the functional capacities of the children to make them self-dependent.
iv. To improve the quality of life of children affected with Spastic Cerebral Palsy.
v. To evaluate the therapeutic effect of Kalyanaka Avaleha in the management of spastic cerebral palsy in children.
vi. To evaluate the therapeutic effect of Karma Basti in the management of spastic cerebral palsy in children.

Iec Registration No

• After receiving institutional ethics committee approval vide letter no DSRRAU/UCA/IEC/19-20/310, this study was initiated.
• The study was also registered in CTRI with registration number CTRI /2021/07/034864.

Study Design

1. Study Type: Interventional
2. Open labelled Study
3. Interventional Groups: Single Arm
4. Purpose: Treatment
5. Timing: 90 days
6. End Point: Efficacy

Material and Methods

Selection of cases

i. Source of patients: Children with cerebral palsy were chosen from the outpatient and inpatient departments (OPD & IPD) of the Bal Roga Department of the attached Ayurved Hospital of the University Postgraduate Institute of Ayurved Studies and Research, Dr. S. R. Rajasthan Ayurved University Jodhpur.
ii. Number of Patients: 35 patients were registered for the present study but 5 patients were dropped out during the study. Therefore, the present study was completed on 30 patients.
iii. Age of patients: Children suffering from spastic cerebral palsy were of age groups one to sixteen years of either sex.
iv. Follow-up: Three monitoring times were done at monthly intervals during the study and follow-up was done after one month of completion of the study.

Diagnostic Criteria Inclusion Criteria

• Children of age groups one to sixteen years of either sex were included which were stratified as 1-5 years, 5-10 years, and above 10 years.
• Diagnosed cases of Spastic Cerebral palsy were selected.

Exclusion Criteria

• Children below 1 year and above 16 years of age were excluded from study.
• Children suffering from any progressive neurologic disorders and any serious illness like meningitis, or encephalitis were excluded from the study.
• Children suffering from various disorders like myopathies, neuropathies, juvenile diabetes mellitus, essential hypertension, and any acute respiratory distress were excluded from the study.

Withdrawal Criteria

Patients who develop life-threatening complications during treatment.

Parents/guardians are not willing to continue treatment.

Untoward Evaluation Criteria

To record adverse reactions an untoward reaction assessment form was developed, and all such adverse reactions were recorded.

Protocol of Research

I. Consent of patient/attendant after making him/ her aware of merits/demerits of trial with the duration of the proposed trial.
II. Fulfillment of inclusion criteria.
III. Registration of the patients.
IV. The investigations mentioned were advised to them before presenting the formulation.
V. The data obtained was clinically deducted and statistically analyzed.

Drugs

For the present study, two drugs were selected. Both drugs were Kalyanaka Avaleha (Table 1) & Prasarni Taila (Table 2) which are described under the chapter of Vata Vyadhi in Bhasijhaya Ratnavalli and Yogratanakar respectively. Preparation of Drug - Haridra, Vacha, Kustha, Pippali, Shunthi, Ajaji, Ajmoda, Yasthimadhu, and Saindhava lavana taken all the ingredients and grind these materials into a fine powder together and administered regularly with Goghrita or honey. Prepared Churna was packed in a sterile polybag of capacity 100 gm and labelled with the date of manufacturing, batch no., and drug license number.

Dose & Duration - Kalyanaka Avaleha was given in the form of Churna in a dose of 40 mg/kg/day in two divided doses as per Young Formula. (Adult dose was considered as 3 grams).

Preparation of Drug

The whole plant of Prasarni collected and coarsely powdered should be placed in a vessel and decocted by adding water (till one-fourth is left) to this, curd, amla kanji in double quantity, and Kalka (paste) made from the following should be added, Tila Taila and subjected to Taila paka procedure to obtain Prasarni Taila (the Kalka Dravyas are- Manjistha, Haridra, Triphala, and Nagarmotha). This Prasarni Taila is highly useful as Nasya and for application. It relieves Ekanga Vata, Apasmara, Unmada, Vidradhi, Mandagni, Tvak-Vata, Sira, Sandhivata, and other Vata Roga. It is also indicated in veterinary practice. It imparts strength and, virility, useful for Vrddha, Bala, Stree, and kings. It is especially indicated in ‘Pangu’ for internal use.

Presentation of Drugs: Prepared oil was packed in a sterile bottle of capacity 100 ml and labeled with the date of manufacturing, batch no., and drug license number.

Aasthapana Basti: The dose of Basti Dravya was calculated using the (Kashyap Samhita/Khilasthan/Bastivisesaniya/109), as shown in the table below. For Aasthapana Basti, doses are mentioned in the given table.

Anuvasana Basti: The dose of Basti Dravya is calculated using the (Kashyap Samhita/khilasthan/Bastivisesaniya/109), as shown in the table below. For Anuvasana Basti, these dosages are mentioned.

Assessment Criteria

• Gross motor function Classification Scale (GMFCS)- to study gross motor function.
• Modified Ashworth scale- to measure the change in spasticity.
• Modified Barthel’s Scale of Advance daily living- to see changes in the Quality of life of Spastic cerebral palsy.

Clinical Study

30 patients satisfying the selection criteria were registered in the study, after following the standard informed consent procedure. Out of these two patients dropped out due to personal family problems and three patients due to acute respiratory distress and suspected pneumonia-like conditions.

Observations

The detailed observations, regarding demographic data, socio-economic status, parental history, family history, personal history, and complete history of the patient regarding the disease were collected as shown in given table below.

Result

Study selection

A total of 605 potentially related references were selected from the three electronic databases. Out of these, 178 were duplicates, and 337 articles were deemed irrelevant through a review of their titles and abstracts. After this initial screening, 90 articles underwent a full-text review for eligibility. Among these, 54 articles were further excluded. The main reasons for exclusion were (I) no desirable study population/ineligible condition, (II) lack of full-text availability, (III) non-English language, and (IV) the treatment method was not mentioned precisely. Finally, a total of 36 papers published between 2006 and 2023 met the eligibility conditions and were counted in the qualitative assessment and systematic review (Figure 1).

Risk of Bias Assessment

The critical appraisal checklist indicates that risk of bias or methodological quality is generally acceptable (Table 1) in most case reports. Although we do not set criteria for low risk of bias for a study based on cumulative scores, risk of bias assessments is reported for each study and separately for each question. Using JBI tool, a total of 18 (50%) cases did not clearly describe the patient’s demographic characteristics; the history of 5 patients (13.6%) was not clearly described and presented as a timeline, and 20 (55%) patients were not clearly described at the time of presentation, and finally explanation of treatment procedure(s) was not clearly reported in only one patient (2.7%). Study characteristics and case demographics: Thirty-six eligible studies reported a total of 37 cases. The retrieved case reports were published between 2006 and 2023, of which almost 70% were published in the last 10 years. Cases were from 14 countries: Turkey (n=8), India (n=6), USA (n=5), South Korea (n=3), Spain (n=3), Taiwan (n=3), France (n=2), and single case report from Greece, Poland, UK, Tunisia, Belgium, Jordan, and Japan (Table 2). Most reported cases were male (24 [65%] of 37), and the median age of study patients was 59±6 years (ranged 2 to 79). Details of bibliographic features of the regained studies, along with the demographic descriptions of the reported cases, are presented in Table 2.

Y, Yes; U, Unclear; N/A, Not applicable

Q1. Were the patient’s demographic characteristics clearly described?

Q2. Was the patient’s history clearly described and presented as a timeline?

Q3. Was the current clinical condition of the patient on presentation clearly described?

Q4. Were diagnostic tests or assessment methods used, and the results clearly described?

Q5. Were the intervention(s) or treatment procedure(s) clearly described?

Q6. Was the post-intervention clinical condition clearly described?

Q7. Were adverse events (harms) or unanticipated events identified and described?

Q8. Does the case report provide takeaway lessons?

Clinical Characteristics of the Reported Patients

Time until developing PNC (day)

The maximum and minimum time intervals between surgery and diagnosis of PNC in the studied patients were 186 and 6 hours, respectively. This time interval was not reported for 8 patients [8,14-19]. The diagnosis of PNC was primarily based on Computed Tomography (CT) scans in 34 (91%) cases. Most of the reported cases were diagnosed within 1 to 4 days (24-96 hours). Among 29-time interval-reported cases, 13 (45%) cases were diagnosed within 1 day, seven (24%) cases were diagnosed on the 2nd day, and five (17%) cases were diagnosed on the 3rd and 4th day. In four patients (14%), it took more than 4 days to diagnose PNC (Table 3).

Signs and Symptoms

The most common complications reported are presented in Figure 2. Headaches were the most common complaint reported by the patients (22 of 37 patients; 59%). Other complaints were separately depicted in Figure 2.

Treatment and Outcome

Of the 37 cases, 26 (70%) underwent conservative treatment and 10 (27%) required surgery. Out of the total 37 patients, 32 (86%) experienced good results after treatment, while 5 (13%) patients had poor results. Among the poor outcomes, three cases were observed after conservative treatment, and two cases occurred after surgery.

Dural tear

There were 23 (62%) reported cases of spinal surgery associated with dural tears which 6 (26%) were classified as tension PNC (Figure 3). Among the 23 cases, 8 (34%) underwent surgery for treatment, and out of these 8 cases, 6 (75%) showed good results after surgery.

Method of confirmation

Of the 37 cases, 30 (81%) underwent CT scan for confirmation, and 2 (5.4%) with MRI. Out of the total 37 patients, 5 (13.5%) underwent both a CT scan and an MRI for confirmation.

Discussion

Pathological accumulation of gas within the cranial space is commonly called PNC [41]. PNC generally has various causes, including trauma, infections by gas-forming bacteria, tumors of the brain or skull-based, cranial operations, along with iatrogenic and idiopathic causes [42-44]. PNC during spinal surgeries is rarely reported [5,29,32]. PNC can be allocated based on the time of intracranial air buildup into acute (<72 h) and delayed (>72 h) [45]. We systematically reviewed all the case reports that occurred after various types of spinal operations, summarized, explained, and compared them from different aspects, including age, sex, type of surgery, clinical symptoms, diagnostic technique, management, and prognosis. Although incidental dural tears, CSF leakage, and in fact any cranial surgery can lead to iatrogenic PNC, spinal operation- induced PNC is seldom reported [20,24,25,27-29]. These cases may have different presentations, including headache, nausea, vomiting, dizziness, altered consciousness or mental status, CSF rhinorrhea, or convulsions [43]. In the present review, 59% of cases complained of headaches. In an observational study on 20 patients with spinal intradural extramedullary (IDEM) tumors who underwent surgical resection, findings showed that the occurrence of PNC was common (90% of patients) after spinal surgeries associated with durotomy, and the reported rate of significant headache was 35% (seven of the 20 patients) [46]. Twenty-five percent of those patients had severe PNC, and the severity of the headache and PNC was positively correlated. Multiple studies have shown that PNC caused by extreme CSF loss usually leads to diminished consciousness, convulsions, and intracranial hematoma [28,47]. Due to the low density of air (about -1000 Hounsfield Units) on CT scans, this modality has become the most reliable imaging modality and highly sensitive technique for the diagnosis of PNC and can detect even 0.55 ml of air inside the skull, and this feature makes CT more accurate than MRI [48,20]. CT scan for diagnosis of PNC had been used for 34 patients of all the cases (92%) in the included reports. In most cases, PNC can be non-operatively treated with bed rest, elevating the head of the bed by 30 degrees, oxygen auxiliary therapy, and numerous other similar approaches [49,50]. Tension PNC is a neurosurgical emergency that mostly needs immediate intracranial decompression by a variety of operative techniques, such as twist-drill trephination or craniotomy [51,52]. In our review, 26 (70%) cases out of the 37 cases underwent conservative treatment, while 10 (27%) required surgery (craniotomy or reoperative spinal surgery and dura repair).

Many hypotheses were proposed to explain the pathophysiology of PNC. Initially, the inverted bottle theory was suggested, which refers to the idea of negative pressure development in the subarachnoid space due to CSF drip, leading to CSF substitution by air until equalization of the intracranial and atmospheric pressures [53]. Then, the ball valve theory was suggested. This theory claims that PNC is credited to a dural defect playing as a oneway valve, leading to air imprisonment in the intracranial cavity [54]. The third theory was the Nitrous Oxide (N2O) theory; N2O is frequently accompanied by anesthesia, leading to tension PNC [55,56]. Another hypothesis indicates that PNC can be developed by gas-forming bacteria [57,58]. In our review, there were 23 (62%) reported cases of spinal surgery associated with dural tears. Out of the 23 cases, 12 (52%) patients were classified as tension PNC. The remaining 14 (38%) reported cases of spinal surgery were not associated with any dural tears. Our study has some important limitations. Firstly, it relies exclusively on case reports and case series, which lack the statistical strength and broad applicability of cohort studies or randomized controlled trials. Secondly, there is a potential for publication bias, as reports tend to focus on severe or atypical cases, while milder or self-resolving instances may be underrepresented. Thirdly, as this condition is essentially a neurosurgical complication, it would have been much better if we had included an academic neurosurgeon among the authors and added her/him to the group of authors. Lastly, the absence of a control group limits the ability to directly compare different treatment approaches. Future studies with larger sample sizes and robust strategies are necessary to better define the signs, outcomes, and optimal treatment strategies for PNC following spinal surgery.

Conclusion

PNC could occur rarely after spinal surgery. The present report is the first systematic review on the signs and symptoms, diagnosis, treatment, and outcome of PNC after spine surgery. Spine surgeons should be aware of this rare complication after spinal surgeries and should not neglect to perform a brain CT scan in cases where unusual symptoms such as headache occur 24 hours after spinal surgery.

Declaration

Conflict of Interest

No potential conflict of interest relevant to this article was declared.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Funding

This research did not receive any specific grant from funding agencies.

Authors’ contributions

F.O.K. worked on the literature search, data extraction, manuscript preparation, and quality assessment. Mah.S.’s role was literature search, data extraction, quality assessment, and manuscript preparation. Mas.S. performed the statistical analysis and quality assessment of the research. S.A.G. worked on data extraction and revision, conceptualization, and supervision of the research. A.O.K.’s role was in data extraction and manuscript revision. E.R. and Maj S. had the idea for the manuscript and worked on the literature search. Maj. S. helped in drafting and critically revising the manuscript. All authors read and approved the final version.

Acknowledgement

Not applicable.

Trial registration

We registered the proposal in the International Prospective Register of Systematic Reviews (PROSPERO). Its registration number is CRD42023467213

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