Key-words:
Herniated lumbar disc - histopathology - low back pain - microdiscectomy - sciatica
Introduction
Low back pain (LBP) is one of the most common chronic problems, affecting millions
of people at different stages of their lives.[[1]],[[2]] One of the possible causes of this condition is the intervertebral disc (IVD) degeneration.[[3]],[[4]] Nevertheless, the clinical picture of different degrees of IVD degeneration is
highly variable, from one person to another.[[4]] Patients may suffer from a severe radicular symptom in their legs with only tolerable,
minimal, or even no LBP.[[4]],[[5]] Moreover, the association between IVD degeneration and the clinical manifestation
of the patients is not fully understood yet.[[1]],[[6]] Except for the diffusion delay noticed across the IVD endplates, pathological disc
degeneration is similar to the aging effect on the IVD.[[7]] The most common cause of radicular/sciatic pain is the lumbar disc herniation.[[8]] The lifetime prevalence of this condition is about 10%, with a variable prevalence
ranging from 1.6% to 43%.[[9]],[[10]],[[11]] This type of pain characterized by downward radiation through the lower limbs,
which is considered one of the main causes of occupational disability.[[12]] In general, the radiological and histopathological characteristics of IVD herniation
and degeneration have been studied well; however, the proper correlation to the patient's
symptoms is not established yet.[[11]],[[13]],[[14]] It is common in clinical practice to find a case with IVD degeneration/herniation
with minimal or no symptoms.[[15]],[[16]],[[17]] Moreover, the herniated disc may exhibit different consistency, including calcification,
which might be associated with complicated surgical intervention and postoperative
complications.[[18]]
In 2002, Boos et al.[[13]] classified the histopathological changes in the degenerating IVDs, following analysis
of cadaveric lumbar specimens, with a wide range of ages ranging from fetal to 88
years. Their study found that rim lesions and edge neovascularization, chondrocyte
proliferation, tears or cleft formation, mucoid degeneration, and granular changes;
are the most common changes in the degenerate IVDs.[[13]] As a result, they proposed a detailed scale for grading the histological changes
in the degenerated lumbar IVDs.[[13]] In 2011, Weiler et al.[[19]] have simplified this scale and validated it using specimens of surgically treated
patients with disc herniation. We based our assessment on the final retained parameters
of the modified scale, which were; cell proliferation, cracks and tears, and granular
changes. We presumed that the consistency of herniated lumbar disc has an impact on
clinical features and postoperative improvement. The objective of this study is to
assess whether the degree of histological degeneration in the sample of lumbar discs
operated on is related to clinical variables as well as the impact on surgical outcomes.
Materials and Methods
Study population and data collection
Period of the study: 24 months.
Inclusion criteria
All the cases that had been diagnosed with disc prolapse and confirmed clinically
and radiologically and scheduled for lumbar discectomy in the department of neurosurgery
during the determined period.
Exclusion criteria
Excluded cases are: Lumbar spine trauma, spondylolisthesis, recurrent disc prolapse,
failed back surgery syndrome, and infection. Moreover, cases not operated by the principal
investigator, and cases that are unable to be correctly traced to their histopathology
specimen, were also excluded.
A randomized double-blind prospective study of lumbar disc prolapse cases initially
included 40 cases in the study. All the included cases with a scheduled lumbar discectomy
in the Department of Neurosurgery, King Fahd University Hospital, Al-Khobar, Saudi
Arabia, during this period were examined histologically and subsequently correlated
to clinical presentation and surgical outcome.
The data from the included cases had been obscured and labeled in two different sets
of groups: A clinical group and a histopathology group. For all variables, a 0–3 scale
was used with 0 = absent, + = mild, 2+ = moderate, and 3+ = marked.[[13]],[[18]]
The clinical investigating team collected data for the clinical group and arranged
the data into tables according to particular variables. This team had no access to
the histopathology results. The variables used in classification are the various motor
(weakness and reflex response) and sensory deficits (LBP, sciatica, paresthesia, and
numbness) with recording the duration of any positive sign/symptom. The outcome of
surgery has been evaluated for all patients with regular follow-up.
Follow up protocol
All patients were discharged postoperatively between the 5th and the 7th day. Patients
were thoroughly examined before discharge (immediate). The patients were scheduled
for outpatient clinics appointment at 1 month, 6 months, and 1 year. They were clinically
examined during their follow-up and followed with radiological imaging.
The histopathology team collected and arranged the data into tables according to particular
variables, for the histopathology group.
Similarly, this team had no access to the clinical data, operative notes, or radiological
data.
Tissue preparation
Regarding the method used in the histopathological evaluation of the samples, four
micron-thick hematoxylin and eosin stained sections, prepared from formalin-fixed
paraffin-embedded disc material and resected from 21 herniated disc patients and eight
cadaveric normal controls. The anatomist who removed these cadaveric discs claimed
the cadaveric discs looked healthy at the time of death, and no sign of herniation
or tear of the annulus fibrosis was noticed, after careful examination.
Data evaluation
At the end of the research period, two teams got together, and the patients' identities
were revealed. Moreover, the correlation between the clinical findings and the histopathological
findings were studied. The histopathological data were semi-quantitatively evaluated
for any morphological changes including, cracks/fissures, vascularization/granulation
tissue, scar tissue, calcification, cartilage cell proliferation (cell clusters),
and degenerated fibrocartilaginous stroma.
Statistical analysis
Three types of correlations were used according to the type of variables. For measuring
the correlation between two continuous variables, the Pearson correlation was used.
The Spearman's rank correlation was used for measuring the correlation between ordinal
and continuous variables, whereas the Point-Biserial correlation was used for measuring
the correlation between nominal and continuous variables. The continuous variables
in the study (Age and HPDS) were checked for normality using the Shapiro–Wilk test.
All statistical analyses were performed in SPSS (Statistical Package for Social Sciences,
version 25, SPSS Inc, Saudi Arabia).
Results
Of 40 patients, 21 patients were included in the study. Nineteen patients were excluded
due to lost follow-up. Of these 21 patients, 18 were male and 3 were female. Patients'
ages ranged from 32 to 72 years (mean = 51 years). In addition to that characteristics,
the most common site of disc herniation was the level of L5–S1 (8 cases), followed
by L4–L5 (7 cases) [[Table 1]]. The histopathological findings of the included patients were compared with a control
group [[Table 2]] and were as follows: the most common changes noted were cracks/fissures [[Figure 1]]a, and degenerated fibrocartilaginous stroma [[Figure 1]]b; they were seen in all study cases (100%) and 7/8 of the controls (87.5%). The
third most common change was cartilage cell proliferation [[Figure 1]]c, seen in 76.2% of the study cases compared to only 37.5% of the controls, thereby
creating a significant difference between them. The proliferation was indicated as
variable numbers of cartilage cell clusters. Scar tissue [[Figure 1]]d, and vascularization/granulation tissue [[Figure 1]]e, were noted in 23.8% of the study cases but were not noted in the controls. Finally,
calcification [[Figure 1]]f was present in 19% of the study cases and 25% of the controls.
Table 1: The baseline characteristics of the included patients
Table 2: Histopathological findings in the study and control groups
Figure 1: (a) Cracks/fissures in disc material. Note also cartilage cell clusters (H and E,
x100); (b) degenerated fibrocartilaginous stroma (pale and fibrillated) (H and E,
x200); (c) cartilage cell clusters. Note also focal scarring and cracks (H and E,
x50); (d) Scarring (H and E, x100); (e) Vascularization (H and E, x200) (f) Calcification
(Note also cracks and degeneration of fibrocartilaginous stroma) (H and E, x100)
The correlation between the baseline characteristics of the patients and the histopathological
findings
The mean of the histopathological degeneration score (HDPS) of all cases was 4.38
(standard deviation, 1.7). There was no significant difference in HDPS between males
and females (P < 0.7). There was a significant correlation between the age of the
patients and HPDS (correlation coefficient = 0.496, P < 0.02) [[Figure 2]]. Moreover, when the patients' ages were classified into groups [[Table 3]], there was also a significant correlation between the age groups and HPDS (correlation
coefficient = 0.535, P < 0.01). There was no significant correlation between the disc
level and HPDS (correlation coefficient = 0.308, P < 0.17).
Figure 2: The correlation between the patients' age and HPDS
Table 3: The correlation between age and the histopathological findings of the prolapsed disc
The clinical findings of the patients
Most cases suffered from LBP and sciatica for 2–6 months, followed by 1 week to 1-month
duration. Numbness was reported in all cases, paresthesia was reported in 17 cases,
motor weakness was reported in 11 cases, and absent of reflexes in 6 cases [[Table 4]]. Cracks/fissures, and degenerated fibrocartilaginous stroma were found in all cases
with different grades scaled as absent, mild, moderate, and marked.
Table 4: Clinical findings of the sample
The correlation between the clinical and histopathological findings
Regarding the correlation between HPDS and the clinical findings, there was no significant
correlation between any of them. The correlation coefficient between HPDS and each
of the clinical findings was as follows: The duration of LBP [[Table 5]] (correlation coefficient = 0.058, P < 0.8), duration of sciatica [[Table 6]] (correlation coefficient = −0.337, P < 0.1), paraesthesia [[Table 7]] (correlation coefficient = 0.111, P < 0.6), motor weakness [[Table 8]] (correlation coefficient = 0.274, P < 0.2), and reflex [[Table 9]] (correlation coefficient = 0.081, P < 0.7). Meanwhile, the correlation coefficient
between numbness and HPDS is not defined because all reported cases were presented
with numbness [[Table 10]].
Table 5: The correlation between low back pain and the histopathological findings of the prolapsed
disc
Table 6: The correlation between sciatica duration and the histopathological findings of the
prolapsed disc
Table 7: The correlation between paresthesia and the histopathological findings of the prolapsed
disc
Table 8: The correlation between motor weakness and the histopathological findings of the
prolapsed disc
Table 9: The correlation between reflex and the histopathological findings of the prolapsed
disc
Table 10: The correlation between numbness and the histopathological findings of the prolapsed
disc
Postoperative outcome
The postoperative prognosis of the patients varied from excellent to poor prognosis,
measured immediately, at 1 month, 6 months, and 1 year. There was no significant correlation
between HPDS and postoperative prognosis. The correlation coefficient and the P value
between HPDS and postoperative prognoses immediately, at 1 month, at 6 months, and
at 1 year, respectively, were as follows: (Correlation coefficient, P value) −0.063,
0.79; −0.102, 0.69; 0.156, 0.54; 0.74, 0.77; respectively. [[Figure 3]] demonstrates the percentage of the total count of the prognoses postoperatively.
Most of the patients (n = 17) had excellent immediate prognosis, where only 2 had
very good, 1 had good, and 1 had poor prognoses. However, the prognosis shifted to
be mostly very good at both 1-month (n = 15) and 6-month (n = 13) intervals. On assessing
the patients after 1 year, 3 of them found to have a poor prognosis. There was no
significant correlation between outcome of surgery and HPDS (coefficient correlation
= −0.08 and P = 0.744).
Figure 3: The percentage of the total count of prognosis postoperatively
In summary, the only significant correlation coefficient noticed was between HPDS
and both the patients' age and age groups. In contrast, there was no correlation between
any of the clinical findings and HPDS, as was the correlation between postoperative
prognosis and HPDS.
The weak correlation between HPDS and the clinical findings may be due to the small
sample size of the study. There is a need for more studies with large sample sizes
for better estimation of the correlation.
Discussion
The normal IVD is anatomically located between vertebral bodies and separated from
them by a thin “cartilaginous endplate.”[[20]] The disc is histologically consisting of nucleus pulposus (inner soft, hydrated
structure) and annulus fibrosus (outer collagenous structure).[[21]],[[22]],[[23]] It has very low cellularity (0.25%–0.5%) composed of chondrocyte-like cells in
the nucleus and inner annulus (many appearing necrotic) and spindly (like tendon cells)
in the outer annulus.[[21]],[[22]],[[23]] It was reported that the disc materials go through certain changes with age.[[24]],[[25]] These changes are the nucleus becomes less hydrated, more collagenous and loses
proteoglycan, the boundary between nucleus and annulus becomes increasingly blurred,
annular-rings thicken, thin cracks and fissures appear in endplate, and nucleus and
annulus.[[24]],[[25]] In the final stages, the matrix becomes replaced by granulation tissue, or scar
ectopic calcification was seen in cases of spinal deformity.[[24]],[[25]]
The current study demonstrated that there are no significant histopathological changes
seen in herniated disc materials within the nucleus pulposus, such as; increase disc
cell proliferation (cartilage cell clusters), degenerated fibrocartilage (pale, fibrillary
stroma), cracks and fissure, calcification, and ossification. Moreover, there was
no significant correlation between the major histopathological changes of the prolapsed
discs and the clinical findings of paresthesia, weakness, and reflex. Although other
clinical features were associated with more histological findings, these changes declined
over time, and the overall correlation was not significant. Furthermore, the different
types of prolapsed discs' histopathological changes have no impact on the outcome
of the surgery. On the other hand, the only correlation found regarding HPDS in our
study was only related to the age of the patient, while gender had no significant
correlation.
The published literature has conflict reports regarding the correlation between histopathological
changes and clinical manifestations, which is consistent with our results, where most
of the correlation faded away over time, and only a few components persisted. Munarriz
et al.[[11]] have conducted a retrospective consecutive analysis of 122 patients who underwent
lumbar disc herniation surgery. They found no significant association between the
degree of histological degeneration and clinical (including age and duration of the
symptoms) or radiological features of the included patients.[[11]] A few other studies have also come to the same conclusion, with no significant
correlation could be established.[[26]],[[27]],[[28]],[[29]] In contrast, Willburger et al.[[30]] have included 55 patients in their investigation of the correlation between the
histologic composition of the herniated disc fragments and clinical features (pain,
disability, clinical signs, and operative findings). Their findings supported a correlation
between the histologic composition of the herniated disc fragments and clinical manifestations,
including; pain, impaired reflexes, and sensory impairment.[[30]]
The limitations of this study may be due to the problems imposed by the small number
of cases evaluated in this study. However, the number is still reasonable in comparison
with the previous studies.
Conclusions
Our study showed that there is no significant correlation between the major histopathological
changes of the prolapsed discs and the clinical findings of paresthesia, weakness,
and reflex. Moreover, the different types of prolapsed discs' histopathological changes
have no impact on the outcome of the surgery. We also concluded that the disc material
undergoes certain degenerative processes with age.
