In our series similar to most studies, [6-9] age and gender of the patient did not correlate with the diagnostic yield, despite some authors reporting that biopsies in the older patients were more likely to result in a definite diagnosis than in a younger patient and a negative influence of the female gender. [5,10,11] In one study where the author uses the age of 40 years as an arbitrary cut-off point, younger patients (<40 years old) had a diagnostic yield of 75.9%, whereas older patients (>40 years old) had a diagnostic yield of 90.6%. 
Lesion’s topography and characteristics
The depth of the lesion does not affect the diagnostic yield in our series. This is similar to the others who also reported that lesion depth does not influence success rate in stereotactic biopsy. [5,19] However, there is a study which reported significantly greater negative diagnostic yield in biopsies of deep-seated lesions.  Anatomical location of the lesion was found to be a significant factor for positive diagnostic yield in some studies [1,9,19,21] and not in others. [6,7,10,16,18] In our series, we found that lesions which were located at the periventricular and pineal region were significant associated with a negative diagnostic yield. This is due to the high incidence of biopsy needle penetration into the cistern or ventricle causing cerebral spinal fluid aspiration during tissue sampling. This loss of negative suction pressure causes loss of tissue catch into the biopsy needle aperture. Thus, a tissue sampling error happens.
The volume of the lesion was reported as one of the factors influencing the diagnostic yield in stereotactic biopsy. [11,21] The smaller the lesion, the greater the likelihood obtaining a negative diagnostic yield and vice versa. Similar results were observed in our series. However, some authors reported size did not matter. [6,16] In our series, the preference of using CRW® frame stereotactic biopsy in smaller lesion is evidenced by the smaller mean volume of lesion of 8cc as compared to frameless brain-suite (12.5cc) and portable Brain-lab® (14cc) stereotactic biopsy. In general, it is recommended to employ frame-based techniques for small lesions in order to minimize the sampling error. [16,17,19,22]
Historically, frame-based technique had been labelled as gold standard in stereotactic biopsy. A recent meta-analysis showed no differences in terms of diagnostic yield and complication between frame-based and frameless stereotactic biopsy.  In our series, we also demonstrate no significant difference in diagnostic yield between the diagnostic yield of the three methods. The main advantage of frame-based technique is shorter operating theater time compared to the frameless technique. Similar findings were reported by other authors as well. 
Up to date, there is no literature discussing surgeon’s experience as one of the factors that may influence the diagnostic yield in stereotactic brain biopsy. From our series, we found significant difference between senior and junior neurosurgeon who guided and performed the stereotactic biopsies. The Group 1 (Senior level) neurosurgeons managed to achieve higher positive diagnostic yield (95%). This group also achieved 100% radiological accuracy compared to 80% by the Group 2 (Junior level) neurosurgeons. We speculate that guidance and involvement by senior, experienced neurosurgeons were associated with higher accuracy and positive diagnostic yield. They had more experience in pre-biopsy planning including target, entry and trajectory selection, more familiarity with the biopsy system and every steps of the biopsy procedure. Stereotactic surgery demands meticulous attention to detail during every step of the procedure.  Variance in neurosurgeons’ proficiency and expertise in performing stereotactic surgery like deep brain stimulation electrode implantation among different institutions/hospitals had been reported as a significant contributor to the accuracy.  Further analysis had ruled out bias between the 2 groups in term of patient’s demographics, lesion’s topography and characteristics, and biopsy methods. In addition, most of the smaller lesion’s biopsies were performed under the senior, experienced neurosurgeons and delivered an acceptable diagnostic yield as mentioned earlier. For the 4 stereotactic re-biopsy cases, all subsequently manage to produce positive diagnostic yield in second biopsy by the help of a senior, experienced neurosurgeon. Guidance and involvement by a senior, experienced neurosurgeon in stereotactic biopsy is definitely helpful in obtaining a positive diagnostic yield and hasten the junior neurosurgeon’s learning curve in stereotactic biopsy procedures.
Limitations of the study
The main limitation of this study is that its non-randomized and single center. Furthermore, the number of biopsy cases is relatively low when compared to other biopsy series. Another limitation that might affect the diagnostic yield and results was the fact that several pathologists were involved with the assessment of the biopsy specimens. Even though that happened randomly, it could have been a confounding factor. There was no frozen section available in this series due to unavailability.
Strengths of the study
We have presented a real-life series involving neurosurgeons of various experience levels, which is reflective of routine practice and analyzed the factors influencing the diagnostic yield. This is probably the first published series reporting on the surgeon’s experience as one of the critically important but underreported factors influencing the diagnostic yield in stereotactic brain biopsy.