
==== Front
Ann Indian Acad Neurol
Ann Indian Acad Neurol
AIAN
Ann Indian Acad Neurol
Annals of Indian Academy of Neurology
0972-2327
1998-3549
Wolters Kluwer - Medknow India

38994791
AIAN-27-398
10.4103/aian.aian_199_24
Original Article
Quantification and Clinical Correlation of Posterior Cranial Fossa Cerebrospinal Fluid Volume in Primary Hemifacial Spasm Using Magnetic Resonance Imaging
Anudeep DDS
Kulanthaivelu Karthik 1
Holla Vikram V.
Kamble Nitish
Yadav Ravi
Pal Pramod Kumar
Mahale Rohan R.
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
1 Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
Address for correspondence: Dr. Rohan R. Mahale, Department of Neurology, First Floor, Neurosciences Faculty Block, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru - 560 029, Karnataka, India. E-mail: rohanmahale83@gmail.com
Jul-Aug 2024
12 7 2024
27 4 398402
16 3 2024
20 4 2024
10 5 2024
Copyright: © 2024 Annals of Indian Academy of Neurology
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
Background and Objective:

Primary hemifacial spasm (HFS) is caused by neurovascular conflict (NVC) at the root entry zone of the facial nerve. Whether reduction of posterior cranial fossa (PCF) cerebrospinal fluid (CSF) volume is a risk factor for HFS is not clear. The study aims at the radiologic assessment of PCF CSF volume and its clinical correlation.

Methods:

A cross-sectional, hospital-based, case–control study was conducted, in which 50 cases of primary HFS and 50 age- and sex-matched controls were recruited. PCF CSF volume was quantified in 3-T brain magnetic resonance imaging.

Results:

The mean age at presentation of cases was 50.7 ± 10.7 years (42–69 years) and controls was 52.4 ± 8.7 years (45–68 years). The mean duration of symptoms was 3.5 ± 1.3 years (1.5–8 years). About 52% of patients had grade 2 (mild) severity of HFS. The mean PCF CSF volume of patients was 13,725.1 ± 909.5 mm3 and controls was 14,458.5 ± 973.5 mm3 (P < 0.001). The mean PCF CSF volume of females with HFS was 13,714.8 ± 852.5 mm3 and female controls was 14,521.8 ± 973.5 mm3 (P = 0.006). PCF CSF volume was significantly associated with the presence of HFS (P = 0.007), the severity of HFS (P < 0.001), and the presence of NVC (P = 0.02).

Conclusion:

PCF CSF volume was lesser in HFS patients and was associated with the presence of HFS, the severity of HFS, and the presence of NVC. Females with HFS had smaller PCF CSF volume. Small PCF CSF volume is a risk factor for HFS, particularly in females with HFS.

Cerebrospinal fluid volume
hemifacial spasm
neurovascular conflict
posterior cranial fossa
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pmcINTRODUCTION

Hemifacial spasm (HFS) is characterized by unilateral, brief (clonic), or prolonged (tonic) contractions of the facial muscles innervated by the facial nerve.[1] The etiology of HFS can be primary or secondary.[2] The neurovascular conflict (NVC) at the root exit zone (REZ) of the brainstem between the artery and the facial nerve is the most common cause of primary HFS.[345] Secondary HFS is due to facial nerve/nucleus damaged by tumors, infections, trauma, demyelination, or secondary to peripheral facial palsy.[67] Primary HFS has been reported to be more frequent in females and the Asian population. Few studies have reported smaller posterior cranial fossa (PCF) cerebrospinal fluid (CSF) volume in patients with primary HFS compared to the controls. These studies are from the Asian region.[8910] However, a study from Poland did not find any difference in the PCF CSF volume between HFS patients and controls. Reduced CSF volume of PCF causes crowdedness in PCF, wherein there is increased pressure of intracranial structures like vessels and the nerve, causing compression of the nerve by the artery. There is discrepancy in the PCF CSF volume according to the race in HFS patients. Whether the reduced PCF CSF volume is a risk factor for the development of NVC in patients with primary HFS needs to be explored. The present study was aimed at the quantification of PCF CSF volume in patients with primary HFS using brain magnetic resonance imaging (MRI) and its clinical correlation with the development of HFS.

MATERIALS AND METHODS

Study design

The study was a cross-sectional, hospital-based, case–control study conducted in the Department of Neurology of a quaternary care center for neurologic disorders in South India.

Study subjects

Fifty cases of primary HFS and 50 age- and sex-matched controls were recruited for the study. The patients were recruited from the outpatient department and the Parkinson’s Disease and Movement Disorders clinic. The sample size was calculated based on the previous study by Chan et al. with a power of 80% and a level of significance of 5%, with a case: control ratio of 1:1.[8] HFS was diagnosed based on the clinical symptom of clonic or tonic contraction of ipsilateral facial muscles. Primary HFS was diagnosed after ruling out secondary causes of HFS, like tumors, demyelination, etc., by MRI of the brain. The controls were recruited from the study hospital; they consisted of hospital employees and outpatient department patient attendants who were voluntarily willing to participate after they were explained the objective of the study. The inclusion criteria were patients with primary HFS who were treatment naïve and willing to participate in the study. Patients with secondary HFS and the presence of MRI contraindications like MRI-incompatible implants, pacemakers, etc., were excluded. The study period was from April 2021 to April 2023 with a total duration of 24 months. A written informed consent was taken from the patients and controls seeking their participation. The institutional ethics committee approved the study (NO. NIMH/DO/IEC-BS& NS DIV/2021). The study was conducted according to the International Ethical Guidelines for Biomedical Research Involving Human Subjects.

Data collection

Neurologic assessment

The sociodemographic and clinical data were collected from all the patients, which included age at presentation, gender profile, age at onset of symptoms, duration of symptoms, presence of aggravating and relieving factors, side of onset of symptoms, topography of facial muscles involved, muscles affected at the onset of symptoms, and severity of HFS. The grading of severity of HFS was based on the 5-point Likert scale, which was as follows: Grade 0- not affected; Grade 1- very mild, occasional twitching, not disturbing; Grade 2- mild, mildly disturbing; Grade 3- moderately severe, frequent blinking, mildly affecting function; Grade 4- very severe, prolonged spasm, severely affecting function.[11]

Radiologic assessment using brain MRI

Brain MRI was done by using a 3-T system (Phillips Ingenia 3.0 T MR system) with standard conventional MRI protocol. The specific sequences included for the study purpose were the three-dimensional (3D) T2-weighted imaging-driven equilibrium radiofrequency reset pulse (DRIVE) (3D-DRIVE) and constructive interference in steady-state (CISS) 3D sequences. The sequence parameters were as follows: Field-of-view (FOV)- 150 ×150 × 65 mm, voxel dimensions- 0.4 × 0.5 × 1 mm; no. of slices- 130; read out- spin echo scheme; Cartesian acquisition; Turbo Spin echo (TSE) factor- 56; Repetition time (TR)- 2000 ms; Time to echo (TE)- 235 ms; Flip angle (FA)- 90°.

Imaging data analyses

PCF volumetry was done in all patients and controls. The volumetry was done by an experienced neuroradiologist (KK). The MRI scans were read blindly on two separate occasions by the same rater. The images were analyzed by the neuroradiologist, who was not aware of the diagnoses, according to the protocol mentioned. The space between the outline of the posterior fossa brain structures that includes the brainstem and the cerebellum (inner boundary) and the posterior fossa endocranium/dural contours (outer boundary) was designated as PCF CSF volume. The PCF volume was quantified using 3D Slicer software version 5.0.3 r30893/7ea0f43. After completion of MRI, the Digital Imaging and Communications in Medicine (DICOM) images were acquired and copied into hard disk. The 3DT2 DRIVE DICOM sequences were converted into NIfTI and uploaded into 3D Slicer. The segmentation of CSF spaces (with the exclusion of the fourth ventricle) was carried out with Porus acusticus as the midpoint using segment editor. The measurement was sampled on 40 slices over a total 2-cm volume slab. The region from the root exit zone (REZ) of the trigeminal nerve to REZ of the vagus nerve of the medulla oblongata was used for the measurement [Figure 1]. By using the paint tool and the level tracing tool, the area to be calculated was marked. The necessary finesse was adjusted using the smoothing tool, and the image was processed to complete the segmentation process. By selecting quantification, followed by the segment statistics, the final PCF CSF volume was obtained [Figure 1].

Figure 1 Axial (a), sagittal (b), coronal (c) MRI images with an area of interest marked in green (white arrow); (d) 3-D reconstructed area of interest (posterior fossa CSF volume). CSF = cerebrospinal fluid, MRI = magnetic resonance imaging

The presence of NVC was assessed using (CISS) 3D sequences both in cases and controls.[12] The location along the facial nerve where NVC was identified was classified as the root exit point (RExP), attached segment, root detachment point (RDP), and cisternal portion based on the anatomic landmarks that are reliably visualized with MRI.

Statistical analysis

Data analysis was done with Statistical Package for Social Sciences V26.0 (SPSS Inc, Chicago, IL, USA) and Microsoft Excel sheet. The Shapiro–Wilk test was used to assess normality of the data. Continuous variables were expressed by mean ± standard deviation with range. Categorical variables were expressed as frequency and percentage. Student’s “t”-test was used to compare the means between the two groups. Categorical variables were analyzed by Pearson’s Chi-square test. The intrarater reliability was assessed using Cohen’s kappa statistics to analyze measurement bias. A multivariate logistic regression analysis was done with PCF CSF volume as the independent variable and age, gender, duration of symptoms, presence and severity of HFS, and presence of NVC as dependent variables. A P-value of <0.05 was considered significant.

RESULTS

A total of 50 patients with primary HFS and 50 age- and sex-matched controls were recruited and analyzed. The mean age of cases and controls at presentation were similar. The mean age at onset was 49.3 ± 10.4 years (range: 42–67 years), and the mean duration was 3.5 ± 1.3 years (range: 1.5–8 years). There was female preponderance in both groups.

Clinical characteristics (n = 50 cases and 50 controls)

The clinical characteristics of cases and controls are presented in Table 1.

Table 1 Clinical characteristics of patients

	HFS cases (n=50)	Controls (n=50)	P	
Age at presentation (years)a	50.7±10.7	52.4±8.7	0.46	
Age at onset (years)a	49.3±10.4	NA	-	
Duration of illness (years)a	3.5±1.3	NA	-	
Females n (%)	30 (60)	28 (56)	0.54	
Female: Male ratio	1.5:1	1.3:1	0.26	
Left HFS n (%)	26 (52)	NA	-	
Aggravating factors		NA	-	
    Anxiety n (%)	40 (80)			
    Talking n (%)	37 (74)			
    Fatigue n (%)	28 (56)			
    Reading n (%)	23 (46)			
    Eating n (%)	18 (36)			
Severity of HFS		NA	-	
    Grade 1 n (%)	7 (14)			
    Grade 2 n (%)	26 (52)			
    Grade 3 n (%)	14 (28)			
    Grade 4 n (%)	3 (6)			
amean ± standard deviation; HFS-Hemifacial spasm; NA-Not applicable

All patients had unilateral HFS with left-sided symptoms more than right-sided HFS symptoms. About 84% of patients had symptom onset in the periorbital muscles, which progressed to involve ipsilateral facial muscles in all patients. None of the patients had lower facial muscle involvement at onset, and eight (16%) had simultaneous onset. Anxiety (80%) was the most common aggravating factor for the facial contraction. About 52% of patients had grade 2 severity of HFS.

Findings of brain MRI

PCF CSF volume and its correlation and NVC

PCF CSF volume and its correlation and NVC are presented in Table 2.

Table 2 Comparison of posterior cranial fossa CSF volume

	Cases (n=50)	Controls (n=50)	P	
Mean PCF CSF volume (mm3)a	13725.1±909.5	14458.5±973.5	<0.001*	
Mean PCF CSF volume in males (mm3)a	13742.6±979.6	14395.3±995.9	0.07	
Mean PCF CSF volume in females (mm3)a	13714.8±852.5	14521.8±973.5	0.006*	
*P≤0.05, significant; amean ± standard deviation; PCF-posterior cranial fossa; CSF- cerebrospinal fluid

Brain MRIs of 50 patients and 50 controls were analyzed to determine the PCF CSF volume and NVC. About 90% of cases had ipsilateral NVC and 10% had bilateral NVC. The anterior inferior cerebellar artery (AICA) (61%) was the most common artery causing NVC, followed by the posterior inferior cerebellar artery (19%), the vertebral artery (13%), and the superior cerebellar artery (7%) [Figure 2]. NVC was present in five controls (10%) caused by AICA. The mean PCF CSF volume of patients with HFS was significantly lower than that of controls (P < 0.001). The mean PCF CSF volume in patients with HFS was 5.1% lesser than in controls. There was a gender difference in the PCF CSF volume between the groups. Females with HFS had significantly lower PCF CSF volume compared to female controls (P = 0.006). There was no significant difference in the PCF CSF volume between males with HFS and male controls and between males with HFS and females with HFS. The measure of intrarater agreement (kappa) was at 0.82. A multivariate linear regression analysis with age, gender, presence of HFS, severity of HFS, and NVC as the dependent variables and PCF CSF volume as an independent variable showed that PCF CSF volume was significantly associated with the presence of HFS (P = 0.007), severity of HFS (P < 0.001), and presence of NVC (P = 0.02). Age and gender were not associated with PCF CSF volume.

Figure 2 Brain magnetic resonance imaging axial CISS 3D image showing neurovascular conflict by (a) anterior inferior cerebellar artery; (b) posterior inferior cerebellar artery; (c) vertebral artery (white arrow). 3D=three dimensional, CISS=constructive interference in steady state

DISCUSSION

This study aimed to determine the PCF CSF volume and its clinical correlation with HFS. The hypothesis was based on previous studies on the PCF CSF volume in HFS that the PCF CSF volume is lower in patients with HFS. The PCF CSF volume was lower in HFS patients compared to the controls, and females with HFS had smaller volume compared to female controls. We found that the decrease in PCF CSF volume was associated with the presence of HFS, the severity of HFS, and the presence of NVC. The previous studies were from Asia and Europe. Chan et al.[8] from Singapore assessed the PCF volume in 41 HFS patients and 41 controls and found that the mean PCF CSF volume was significantly lower in patients with HFS (11.4% lower) than in controls. They reported that the small PCF CSF volume was associated with HFS and younger age, and that the female gender was associated with small PCF CSF volume. Similarly, Cheng et al.[9] studied the PCF CSF volume in 102 patients and 51 control subjects and found smaller PCF CSF volume in patients; also, women with HFS had smaller PCF CSF volume. The mean PCF CSF volume in patients with HFS was 11.8% smaller than in control subjects. They suggested considering posterior fossa anatomic features when deciding surgical option for HFS. These studies from Asia have shown that reduced PCF CSF volume is a risk factor for HFS. However, Rudzińska et al.[13] studied 60 HFS patients and 60 healthy volunteers matched by sex and age and found no significant differences in PCF CSF volume between the patients and controls. Women had lower PCF CSF volume both in HFS and control groups. Women with HFS have smaller PCF CSF volume, and smaller PCF CSF is a risk factor for the occurrence and severity of HFS, as exemplified by the previous studies and the current study.

The epidemiological studies from the USA and Norway have shown that the mean age of onset of HFS is 54 years, which is similar to our study with a mean age at onset of 50 years.[1415] Colosimo et al.[16] and Rosenstengel et al.[17] also reported a mean age at onset of 56 years. However, Batla et al.[11] from the northern part of India reported a younger age at the onset by a decade earlier (43 years) and Wang et al.[18] showed mean age at the onset of 47 years. The mean duration of illness was longer by about 10.5 years in the study by Colosimo et al.[16] and 8 years in the study by Rosenstengel et al.[17] We found a relatively lesser mean duration of illness of 3.5 years probably due to earlier seeking of treatment. An epidemiological study from the USA showed a female:male ratio of 2:1 and from Norway showed a female: male ratio of 1.9:1.[1415] Batla et al.[11] reported equal frequency of primary HFS in males and females. We had female preponderance with a ratio of 1.5:1, which is similar to other studies. AICA was the most common artery causing NVC in our cohort.[1920] Campos-Benitez and Kaufmann[21] studied NVC in 115 HFS patients who underwent microvascular decompression and found that AICA and Posterior inferior cerebellar artery (PICA) are the most common arteries causing NVC. The most vulnerable area of the facial nerve for NVC is the segment from RExP at the pontomedullary sulcus to the transition zone 2–4 mm distal to RDP.[19]

The strength of the study was the radiologic assessment of PCF CSF volume in primary HFS patients as there is a scarcity of studies evaluating the same. The limitations were the small sample size and lack of measurement of PCF CSF volumetry by a double rater, which leads to a possibility of measurement bias.

CONCLUSION

PCF CSF volume was significantly lower in HFS patients and it was associated with the presence of HFS, severity of HFS, and the presence of NVC. Women with HFS had smaller PCF CSF volume. AICA was the most common artery causing NVC. As HFS is due to the vascular conflict of the facial nerve in PCF, decrease in the PCF CSF volume causes crowdedness in PCF and compression of the nerve by the vascular contact. A radiologic assessment of PCF CSF volume in patients with HFS may be included in the evaluation of HFS, apart from the assessment of NVC, before the microvascular decompression of the facial nerve. A larger cohort of patients and longitudinal follow-up are needed to confirm the findings of this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.
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