Introduction

The enclosure of the brain and spinal cord by the bone causes an expansion of their contents by a space occupying lesion to distort CNS tissues [1]. Intracranial space occupying lesions (ICSOLs) which are diverse, are mass lesions within the brain with different aetiologies [2]. Depending on their size and other characteristics, they may or may not cause disturbances to normal brain function, and the onset of the symptoms tends to be insidious for most ICSOLs. The eye, being an embryological and anatomical outgrowth of the brain, serves a focal point for different clinical manifestations of mass lesions involving the brain. It is important to note that while neoplastic lesions may be the most common form of intracranial space occupying lesions, other forms which are non-neoplastic include inflammatory, infective, congenital, parasitic, hematomas, vascular amongst others [3,4] and could affect different brain areas [5]. Usually, the most common and worrisome presentation for the patient is headache [3,6] However, behavioral changes, vomiting with or without nausea [5], speech or vision deficit, endocrine abnormalities, convulsion, vertigo, tinnitus and gait disturbances are other common general manifestations [5,7-9]. It is however important to note that ophthalmic manifestations usually present earlier than the general manifestations7 making the role of the Ophthalmologist crucial in the early detection of these pathologies. However, in low income or developing countries, the presentation pattern might be altered giving room for more advanced or bizarre patterns of ophthalmic and general manifestations or a combination of both. Common ophthalmic manifestations include diminution of vision, proptosis, diplopia, drooping of the eyelids, optic atrophy, papilledema amongst others [5,6,10]. In extreme cases it could result in blindness if not detected on time [11,12]. Blindness is a common presentation of brain tumor in developing countries [13]. It is also important to note that the first clinical presentation of ICSOL may be a visual dysfunction [14].

Although imaging diagnosis are the gold standard in detecting the presence and location of intracranial space occupying lesions, and histopathology the gold standard in determining the type, clinical and statistical correlation of the ophthalmic and general manifestations of ICSOL could be a very useful algorithm in early detection of the presence of these lesions, particularly among patients who are unable to undergo the requested imaging on time due to cost constraints. While clinical correlation helps to measure directly the implication of one clinical variable on the other, statistical correlation may help more objectively to determine if the observed relationship has any statistical significance. While these does not necessarily translate to causation, it may help to determine if any relationship actually exists between the observed variables. Regarding statistical correlation, in a retrospective study by Valduvieco et al [14] to evaluate the correlation between MRI and gyneacological examination findings in assessing the local response in 75 cervical cancer patients treated with chemotherapy/radiotherapy, found a correlation of 0.68 (60%) between MRI findings and clinical findings at three months and a further increment of 0.86 (82%) at six months. The conclusion was that physical examination remains an important tool in the evaluation of the local response to radiotherapy and chemotherapy in cervical cancer patients [15]. In a study by Gotecha et al [15], it was found that 73.4% of the patients with ICSOL had ophthalmic manifestations [16]. It is important to note that both ophthalmic and general manifestations, either singly or in combination is common in patients with ICSOL. While eye signs alone may or may not be sufficient to detect ICSOL, when combined with general manifestations, it can heighten the clinical detection of an ICSOL. In addition to this, it would be of tremendous clinical assistance if there could be a way to correlate the presence and types of these ocular and general manifestations to the location of the intracranial space occupying lesions both clinically and statistically. This would go a long way in ensuring timely identification, management and a better prognosis for the individuals affected. This is particularly so in individuals from developing countries in which diagnosis of these lesions are delayed due to the unavailability of funds necessary for imaging. This approach can be a useful screening tool for the presence and location of an ICSOL.

Methodology

Study Design

This study is a hospital based cross-sectional descriptive study. Having obtained ethical approval from the Health Research Ethics Committee of Lagos State University Teaching Hospital, 124 patients with intracranial space occupying lesions were consecutively recruited and studied. This was to find out the clinical and statistical correlation if any between the ophthalmic and general manifestations of ICSOLs to their presence and location.

Study Population

The study was carried out among 124 patients diagnosed with intracranial space occupying lesions attending the Neurosurgical and Ophthalmology clinics, as well as those on the neurosurgical ward in Lagos State University Teaching Hospital (LASUTH), are 18 years or above, meet the eligibility criteria and willingly give consent to participate in the study.

Study Duration

The study was carried out between Dec 2019 and May 2020.

Study Procedure

Patient Recruitment

Having obtained ethics approval to commence the study, patients with ICSOL (both old and new cases that meet the eligibility criteria), on follow up or new appointments in both the neurosurgical and ophthalmology clinics, as well as the neurosurgical ward that give their consent were consecutively recruited by the researcher till the sample size was attained. All suspected cases of ICSOL seen in the eye clinic were referred to the neurosurgeons for review and confirmation. Only patients with a radiological diagnosis of ICSOL confirmed by the Neurosurgeons were recruited. On the day of recruitment, a detailed history and examination of the patient including the neurological examination, ocular examination, confrontational perimetry and other adjunctive tests were done by the researcher. Their case notes were checked to obtain any additional information relevant to the study such as other neurological examinations done, the investigations done and treatment received so far. The patients were thereafter dilated and a dilated fundoscopy with binocular indirect ophthalmoscope was done. Patients however fit for automated perimetry were given a date for the test.

History Taking: A detailed history of the presenting complaint was obtained.

• General Examination: This was done, noting for the presence of the speech pattern, weakness of any part of the body, swelling in other parts of the body, whether acutely or chronically ill looking.

• Neurological Examination: this includes gait, consciousness and alertness, orientation in time, place and person, complete cranial nerve examination of all the 12 cranial nerves and mental state examination was done.

• Ocular Examination

• Visual Acuity was done for distance and near vision using Snellen’s chart and illiterate E chart.

Anterior Segment Examination

This was done with the aid of the pen torch and slit lamp and included an examination of the lids, globe for alignment and movements, extra-ocular motility, and the cornea and pupil for any abnormality.

Adjunctive Tests for Assessing Optic Nerve Function

Light brightness test and colour vision tests were done using a bright pen touch and ishihara chart respectively.

Posterior Segment Examination

This was done with a binocular indirect ophthalmoscope after dilating the pupils with 1% tropicamide eye drop.

Confrontational Perimetry

Confrontational visual field test was done for all the patients unable to undergo automated perimetry.

Automated Perimetry

An automated visual field test was done using the Humphrey visual field analyzer for patients who are fit for the procedure.

Investigations

Radiological Investigations [X-rays, Computerized Tomography (CT), Magnetic Resonance Imaging (MRI), Magnetic Resonance Angiography (MRA) and other laboratory tests requested and carried out as part of clinical management of the patient by the neurosurgical team was assessed.

Data Management Plan

After a radiological confirmation of a clinical diagnosis was determined, by the Neuroradiologist, the ophthalmic features noted were statistically correlated with the anatomical location of the lesion (as confirmed by neuroimaging) and the general manifestations seen. Logistic regression was used in the analysis of this objective. A clinical correlation of the ophthalmic manifestations noted as well as the general manifestations were done for each ICSOL based on the location of the lesion.

Data Collation and Analysis

Data was entered and thereafter analyzed using IBM Statistical Product and Service Solutions (SPSS) version 25 software. Categorical variables findings were noted using frequencies and percentages. The relationship between the location of the ICSOL and the manifestation seen was analyzed using logistic regression. A ninety percent confidence interval and a level of significance of <0.05 was used. Charts showing the clinical correlation were drawn using Microsoft excel.

Results

A total of 132 participants were recruited, with 124 fully studied. Majority of the study participants were within the age group of 41-60 years, 82 (66.1%) patients, while male was the preponderant gender with 69 (55%). With regards to the general presenting symptoms by study participants the commonest was visual problems in 118(95.2%), followed by headache in 79(63.7%), change in behaviour in 27(21.8%),balance problems in 24(19.4%), ringing sensation in the ear in 22( 17.7%), seizures in 18(14.5%), speaking abnormalities in 18(14.5%), vomiting in 18(14.5%), change in libido in 13 out of 82 males (15.8%), change in menstrual pattern in 5 out of 55 females (9.0%),and nausea in 2(1.6%). The most common ICSOL in this study was hematoma in 31(25.0%) meningioma was next in 28(22.6%), pituitary adenoma in 18(14.5), intracranial abscess in 10(8.0%), craniopharyngioma in 8(6.4%), metastasis 7(5.6%), glial tumor 7(5.6%), aneurysm in 5(4.0%),cerebellopontine tumors and sinoorbital tumors in 3(2.4%),and cyst and schwanoma in 1(0.8%). Table 1 shows the general examination of the study participants, Table 2 shows the location of the ICSOL by imaging, Table 3 shows the clinical correlation of the ocular and general manifestations to the location of the ICSOL, together with the affected cranial nerves and the visual field patterns, Table 4 shows the statistical correlation of the general symptoms to the location in the brain, Table 5a to 5d shows the statistical correlation of the ophthalmic manifestation to the location in the brain and Table 6 shows the visual field patterns among the study participants. Regarding the correlation of ophthalmic manifestations seen to the location of the ICSOLs, the locations noted from the imaging findings include Sella/Suprasellar lesions 36 (29.0%) was the commonest location, followed by frontal lobe 19 (15.3%), mixed location in 10 (8.0%), amongst others.

Discussion

Intracranial space occupying lesions are mass lesions within the cranial cavities with different aetiologias [2]. While the etiology of ICSOLs might be different, the implications of these lesions on the visual pathway and their connections are diverse and warrants prompt detection and timely management irrespective of the geographical characteristic of the sufferer. For the demographics, majority of the participants in this study were in the middle age group with age range between 41 to 60 years, followed by age groups 18 to 40 years and the least age group affected in this study was age range over 60 years. This could be due to a significant percentage being due meningiomas which although has an age of onset usually between 19-40 years, may present in the middle age as seen in our study due to the characteristic slow course of the lesion as well as late presentation of patient which is rampant in our environment. Furthermore, pituitary adenomas which were also many in our study are common between ages 41-60. However, the study by Datta et al [17] is different stating a higher percentage of neoplastic lesions (which constitutes a higher percentage of the cases seen in this study) between 15 to 24 age group and non -neoplastic lesions between 55-64 years [17]. This discrepancy in age in our study could also occur due to a substantial proportion of non-neoplastic lesions including hematomas and abscesses in this study and the fact that patients younger than 18 were excluded from the study. It is like a study in Pakistan, which showed most cases in the sixth decade [18]. It is also similar to a study by Raju et al, [19] which showed maximal incidence in the age group 40 to 50 years.10 For the sex, males were found to be more affected compared to females in this study, with a male to female ratio of 1.45 : 1. This is similar to the studies by Datta et al [17], with a male: female ratio of 1.27:1,9 Mwang’ombe et al [19] in Kenya with a ratio of 1.4:1,13 and Onakpoya et al [7] in Nigeria with 60.2% male and 39.8% females. However, it is different from the studies by Raju et al [19] which showed more females (60%) being more affected than men. Furthermore, black race might also be a factor in the proportion of cases of meningioma seen in our study, as African Americans have been found to have higher incidence of meningioma in the U.S compared to other ethnicities [20-22].

The etiology of ICSOLs and peculiarity of presentation varies. The commonest type of intracranial space occupying lesion seen in this study was intracranial hematomas seen in 31 (25.0%), followed by meningiomas and pituitary adenomas in that order. This is like the study by Datta et al, [17] that showed intracerebralhemorrhage (hematoma) as the commonest ICSOL seen in their study. The prevalence was however higher in the study by Datta et al [17] with 53.3% compared with the prevalence in this study. This is different from the study by Shende et al [9] with glioma and meningioma being the commonest lesion. On a brain region by region basis, the findings for sella/suprasellar lesions in our study showed reduced visual acuity, blindness and proptosis as common features. The notable optic disc findings were papilledema, glaucoma like optic disc pallor and cupping, temporal palor and optic atrophy. Menstrual irregularities and reduction of sexual performance was noted among participants in this group as well. This is like findings in literature. However, additionally in our study, strabismus was seen in three cases with pituitary macroadenoma and four cases in suprasella meningioma. This might be due to the humongous nature of the masses and involvement of the extraocular muscles, cranial nerves with extension of the mass. The sella/suprasellar lesions in this study were meningiomas, craniopharygiomas and pituitary adenomas. Many pituatary adenomas seen were macroadenoma with very poor vision on presentation. This is like the study by Kitthaweein et al [23] which showed a high proportion 59(86%) with visual loss. Abnormal light brightness, colour desaturation and colour vision were also common in this group. The possible explanation might be the marked involvement of the optic nerve in the pathological process and its implication on colour vision. Cranial nerves most affected in this location in his study were II, III, IV. This is not unexpected for cranial nerve II, considering the pathway of these cranial nerves and the location of these lesions. Visual field patterns were varied and included some unsual patterns such as binasal hemianopia, isolated right and left temporal hemianopia as well as total scotoma. This is different from purely bitemporal hemianopia which is the typical pattern of visual field defect in sella/suprasellar lesions in literature.

For the cortical lesions, different areas of the cortex had varied presentations. The ophthalmic features for lesions involving the frontal lobe include reduced visual acuity, blindness, diplopia, proptosis, gaze abnormalities, strabismus, nystagmus among others. Nystagmus in this group was noticed more commonly among those with abscesses and hematomas. Cranial nerve most commonly affected here were II, III, IV, VI and VII. The visual field patterns noted here were total scotoma, altitudinal visual field defects, temporal or nasal field defects and peripheral constriction. Headache, seizure and change in behavior were common accompanying symptoms in this group. These accompany general manifestations are however like findings in literature. The visual findings for those with parietal lobe lesions include reduced visual acuity, pupillary abnormalities and disc changes which include temporal palor, papilloedema, pale and cupped disc. Affected cranial nerves noted [3,6,7]. Common visual field changes noted were homonymous inferior quadrantanopia, homonymous hemianopia, amongst others. Homonymous inferior quadrantanopia is like the visual field findings of parietal lobe lesions in literature, however the other visual field findings above were also noted amongst the participants with these lesions in this study. Temporal lobe lesions also had reduced visual acuity, diplopia, occasional pupillary abnormality, temporal palor, and papilledema. Cranial nerves affected here were III, VI, VII, VIII. Visual field changes seen were homonymous hemianopia, homonymous superior quadrantanopia, right or left superior quadrantanopia, homonymous inferior quadrantanopia was seen in a case of mixed location involving the parietotemporal lobe. Those with lesions involving the occipital lobe had reduced visual acuity in both eyes, pupils were reactive, no abnormality noted and pink disc in both eyes. No cranial nerve abnormality noted. The general manifestations varied with behavioral change and seizures in both frontal and temporal lobe lesions, tinnitus and paresthesia in parietal lobe and no general manifestations noted for the occipital lobe lesions. While the general manifestations were like many findings in literature, the ophthalmic manifestations had some variations with both typical and atypical findings noted in our study.

For the posterior fossa lesions, uniocular blindness was seen in two cases, nystagmus in all the cases, gaze abnormalities with poor smooth pursuit and saccades and papilloedema was also noted. Visual field changes were blindness with total scotoma, peripheral constriction, enlarged blind spot. Facial nerve palsy was seen in all cases and two had hearing deficit. These findings are like the study by Phillips et al [24] in which all the patients with posterior fossa tumors had nystagmus, as well as problems with saccades and smooth pursuit. It is however different in terms of the diversity of visual field findings. General findings in this group were gait abnormalities, hearing impairment and facial nerve palsy. Unlike typical findings in posterior fossa lesions, [22] many in this group did not have headaches. However, similar to this finding [22] gait abnormalities were quite common in this group. Regarding the other locations for the ICSOLs. Patients with brain stem lesions had reduced visual acuity, anisocoria, ipsilateral gaze palsy in one case and pink disc. The cranial nerves affected were II, III, IV, V, VI, VII, VIII, IX, X. Visual field patterns noted include normal, total scotoma, homonymous hemianopia and altitudinal field defect. General manifestations noted were voice changes and facial nerve palsy. Patients with ICSOL with involvement of the optic nerve had varied visual presentations including reduced visual acuity, blindness, proptosis, pupillary abnormality and notable disc changes. Patients with basal ganglia lesions had diverse findings such asnystagmus, gaze abnormalities, normal pupils and pink disc. Visual field defects noted were homonymous hemianopia and altitudinal field defects Parasagittal lesions showed reduced visual acuity, nystagmus, diplopia, gaze abnormalities, pupillary abnormalities, disc changes include papilloedema. Visual field defects were enlarged blind spot, peripheral constriction. Cranial nerves affected were II, VI and X. Cranial nerve VII palsy found in many cases with haematomas. While some of these findings might agree with typical presentations for these lesions in literature, some findings were atypical.

In this study, for statistical correlation of the general symptoms to location of ICSOL, there was statistically significant association between behavioral change and change in speech and the location of ICSOLs. This might imply that the presence of these manifestations in a case of suspected ICSOL, might help localize these lesions. There was however no significant association between location of ICSOLs and headache, vomiting, seizure, and vision problems (non-specific), signifying a possible lack of localization criteria in the presence of these symptomatic combinations. For the statistical correlation of ophthalmic manifestations to location of ICSOL, there was statistically significant association between cranial nerve IV palsy in the right and left eye, strabismus in the right eye, nystagmus, cranial nerve VII palsy and pupil reactivity to light and the location of ICSOLs. This might also suggest that when these findings are present, the localization of ICSOL might be possible. There was however no significant association between visual acuity, ptosis, cranial nerve III palsy, cranial nerve IV palsy, proptosis, strabismus in the left eye, gaze abnormalities, skew deviation, saccades, smooth pursuit, diplopia, exposure keratopathy, cranial nerve V palsy, palor and colour vision and the location of ICSOLs.

This study has shown the clinical and statistical correlation of the observed ophthalmic and general manifestations of ICSOL to their location in the brain. While the clinical correlation might suggest a possible clinical link, the statistical correlation might imply the need for large scale studies on causation for a definitive link. Although correlation those not equal causation, some knowledge on these could help further predict the likely presence of ICSOLs as well as their possible locations. This is particularly relevant in low resource settings where undergoing prompt imaging investigations remain a challenge. A key limitation to this study was that while a significant attempt was made to note the ophthalmic and general manifestations of ICSOL and correlate this to the presence and location of these lesions in the brain using an observational study, a large-scale randomized case control study might be better able to demonstrate this difference. Furthermore, this study utilized statistical correlation of the ophthalmic and general manifestation to the location in the brain which does not show causation. In conclusion, intra-cranial space occupying lesions have diverse aetiology and occupy different regions in the brain. Findings from this study revealed some features that could aid in the clinical detection of ICSOLs using ophthalmic and general manifestations particularly in low resource settings, and has shown a statistically significant association between change in behavior, change in speech, for general manifestations and cranial nerve IV palsy in the right and left eye, strabismus in the right eye, nystagmus, cranial nerve VII palsy and pupil reactivity to light, for ophthalmic manifestations and the location of ICSOLs. It also showed a clinical correlation of the ophthalmic and general manifestations to their locations in the brain, emphasizing the possible use of this knowledge in the early detection of ICSOLs in relevant settings.

Acknowledgement

The author of this manuscript acknowledges everyone that has contributed to making this research work successful.

Sources Of Funding

No funding was received for this work from any organization or group.

References

1. Betmouni Samar, Love Seth (2004) Pathology of space-occupying lesions of the CNS. Surgery (Oxford) 22(3): i-iv.
2. Hema N, Ravindra R, Karnappa A (2016) Morphological patterns of Intracranial lesions in a Tertiary care Hospital in North Kamataka. A clinicopathological and immunohistoclinical study. J clin DiagnRes 10(8): ECO1-5.
3. Sajjad A, Naroo G, Zafar K, Zulfiquar A, Bina N, et al. (2018) Space occupying lesions of the Brain and clinical manifestations with subtle neurological symptoms in emergency department. Journal of advancement in Medicine and Medical Research 26(3): 1-8.
4. Soomro Bashir, Khalid S, Alvi S. Shafaq (2014) Analytical study of clinical presentation of intracranial space-occupying lesions in adult patients.Pakistan Journal of Neurological Sciences 9(3): 01-07.
5. Cappa Stefano, Lisa Cipolotti (2012) Cognitive and behavioral disorders associated with space-occupying lesions. Cognitive Neurology: A clinical textbook (Oxford, 2008; online edn, Oxford Academic pp: 161-182.
6. Onakpoya O, Komolafe E, Akintomide F, Ajite K, Komolafe M, et al. (2009) Ophthalmic manifestations of patients with Intracranial tumors. Afr J Neurol Sci 28(1).
7. Suchimita Mishra, Souvagya Panigrahi, Suprava Das, Yamijala Neha Srija, Pradeep Kumar Panigrahi, et al. (2024) Demographi Profile and Neuro-Ophthalmic Manifestations in Primary Intracanial Tumors in Adults Patients: An Observational Study from a Tertiary Care Centre in Esstern India. TNOA Journal of Ophthalmic Science and Research 62(4): 431-436.
8. Rure Daisy, Kaithwas Nisha, Kushwah S Suneel, Mishra Nimisha, Mishra Dheerendra, et al. (2023) Psychiatric presentation in undiagnosed intracranial space-occupying lesions: A case series. Ind Psychiatry J 32(Suppl 1): S268-S272.
9. Vrushali Shende, Sandeep Iratwar, Sachin Daigavane (2019) Ocular manifestations in Patients with Intracranial Space-Occupying Lesions. Journal of Datta Meghe Institute of Medical Sciences University 14(3): 119-124.
10. Ijeoma OO, Eweputanna LI, Eweputanna CC (2020) Intracranial lesions leading to impaired vision and blindness in Aba, South-East Nigeria. East Africa Medical Journal 97(8).
11. XP Zhou, MY Zhao, YJ Ma (1987) Blindness from intracranial tumors: a clinical analysis of 60 cases. Am J Otom Physiol Opt 64(5): 329-332.
12. Tagoe NN, Essuman VA, Fordjuor G, Akpalu J, Bankah P, Ndanu T (2015) Neuro-Ophthalmic and Clinical Characteristics of Brain Tumors in a Tertiary Hospital in Ghana. Ghana Med J 49(3): 181-186.
13. Thool Archana, Walavalkar Ruta (2021) Visual Dysfunction as the First Presentation of Oligodendroglioma- A Case Report.
14. Valduvieco Izaskun, Biete Albert, Rios Ivan, Llorente Richardo, Rovirosa Angel, et al. (2013) Correlation between clinical findings and magnetic resonance imaging for the assessment of local response after standard treatment in cervical cancer. Reports of Practical Oncology & Radiotherapy 18(4): 214-219.
15. Gotecha Sarang, Kotecha Megha, Punia Prashant, Chugh Ashish, Shetty Vridhi (2022) Neuro-Ophthalmic Manifestaions of Intracranial Space Occuping Lesions in Adults. Beyoglu Eye J 7(4): 304-312.
16. Datta P, Sutradhar S, Husain I, Datta R, Anwar A, et al. (2019) Clinical patterns of Intracranial space occupying lesion in tertiary level hospital. J Dhaka Med Coll 28(1): 17-22.
17. M Ejaz Butt, Saeed A Khan, Naseer A, Chaudhry, GR Qureshi (2005) Intracranial space occupying lesions. A morphological analysis. E:/ Biomedica 21: 31-35.
18. Raju K, Anju A (2009) Ocular manifestations of intracranial space occupying lesions. A clinical study: Kerala J ophthalmol 21(3): 248-252.
19. Mwang’ombe N, Ombachi R (2000) Brain tumors at the Kenyatta National Hospital, Nairobi. East Afr Med J 77(8): 444-447.
20. Gabriel A, Batey J, Capogreco J, Kimball D, Walters A, Tubbs R (2014) Adult Brain Cancer in the U.S Black Population: A Surveillance, Epidemiology, and End Results (SEER) Analysis of Incidence, Survival, and Trends. Med Sci Monit 20: 1510-1517.
21. Jung Tae-Young, James T Rutka (2012) Schmidek and Sweet Operative Neurosurgical Techniques (Sixth Edition) 1: 654-668.
22. Keogh B, Henson J (2012) Clinical Manifestations and Diagnostic Imaging of Brain Tumors. HematolOncolClin North Am 26(4): 733-755.
23. Kitthaweesin K, Ployprasith C (2008) Ocular manifestations of suprasellar tumors. J Med Assoc Thai 91(5): 711-715.
24. Phillips JO, Shaw DW, Ellenbogen RG, Weiss AH (2004) Oculomotor findings in posterior fossa tumors.Invest. Ophthalmol Vis Sci 45(13): 2529.