spinal cord diseases - myelitis - paraparesis - myelopathy
doenças medulares - mielite - paraparesia - mielopatia
Non-traumatic spinal cord diseases constitute one of the most common groups of neurological
diseases in medical practice[1]. It is a broad and heterogeneous group of etiologies, summarily divided into compressive
and non-compressive, among which include infectious, demyelinating, neoplastic, metabolic
and vascular diseases and congenital malformations. Medical comorbidities and epidemiological
data are important tools combined with complete physical examination to determine
specific diagnostic suspicion[2]
,
[3]
,
[4].
Most diagnostic algorithms do not take into account individual data or prevalence
each disease or prevalence in a given population; rather they involve information
on clinical course of myelopathy, neuroimaging and other complementary investigation.
Although we apply the same diagnostic flowcharts in our population, many etiologies
are known to be distinct in our context, notably the higher prevalence of infectious
causes. Moreover, the use of flowcharts without appropriated clinical context increases
the health system costs, while maintaining the high percentage of undefinited etiology
cases. The aim of this study was to describe a large cohort of patients with non-traumatic
myelopathy from a neurological reference service in Brazil.
METHOD
A retrospective observational review from 1050 medical records of patients was performed
and 166 patients with suspected myelopathy. Our study was approved by our institutional
Ethics Committee. All patients were followed for at least 2 years and underwent clinical,
laboratorial, neuroimaging and genetic evaluation. Inclusion criteria were patients
of any age or gender, who presented at the initial clinical examination with one or
more clinical signs suggestive of possible myelopathy: sphincter dysfunction, paraparesis,
tetraparesis, sensory level, clinical compromise of multiple ascendants or descendants
tracts and/or a specific spinal cord syndrome (complete, posterior cord, anterior
horn, foramen magnum, central cord, conus medullaris, cauda equina, Brown-Séquard
and tractopathies) [2]
,
[3]
,
[5]
,
[6].
Information on age, gender, age at onset, disease duration, first clinical complaint,
personal and familial medical history, myelopathy severity (European-Myelopathy Score
(EMS), Cooper-myelopathy-scale (CMS), Prolo-score and Nurick-score)[7], neuroimaging studies (spinal cord MRI, eventually all neuraxial), general and specific
laboratory exams (routine rheumatology profile; serum vitamin B12; angiotensin-converting
enzyme; CMV antigenemia assay; HIV, HTLV-I/II, syphilis, hepatitis B and C serologies;
serum very long-chain fatty acids; serum and urinary ceruloplasmin and copper; serum
anti-aquaporin-4 antibody), specific cerebrospinal fluid studies (viral and syphilis
serologies and oligoclonal bands)[3]
,
[5]
,
[8], and electroneuromyography study findings (in doubtful etiology or need for additional
diagnostic strategy) were compiled.
RESULTS
Clinical and epidemiological data
There was a slight male predominance (53%) in our sample. The mean age at diagnosis
48.5 ± 16.2 years and mean disease duration of 49.9 ± 34.5 months.
The most common complaints were paraparesis (41.6%; n = 69) and paresthesia/numbness
in the lower limbs (36.1%; n = 60), followed by hypoesthesia in the lower limbs (18.7%;
n = 31), back pain (17.5%; n = 29), monoparesis (13.8%; n = 23), lower limbs pain
(12.0%; n = 20), imbalance (9.0%; n = 15), recurrent falls (7.2%; n = 12), sphincter
disturbance (6.0%; n = 10), stiffness in the lower limbs (5.4%; n = 9) and tetraparesis
(4.8%; n = 8).
Most patients presented progressive (53%; n = 88) and stable (45.2%; n = 75) clinical
courses, with only 2% (n = 3) of cases presenting recurrent deficits, all revealing
demyelinating disease. Only half of patients presented sphincter impairment complaint
(51.2%), more frequently urinary incontinence (35.5%) and constipation (36.7%). Fecal
incontinence was observed in less than 10% of cases. Double sphincter impairment was
most common in neuroschistosomiasis, possibly related to lesions near the conus medullaris.
Evidence of sensory level in the physical examination was absent in 73.5% (n = 122)
of cases, and the most common level was the thoracic (20.5%; n = 34). Cervical level
was rarely observed (1.8%; n = 3).
Regarding previous medical history of chronic clinical and surgical conditions, draws
attention the fact that only 4% of patients do not have medical backgrounds, as well
as the high prevalence of previous malignancies (13.8%) ([Table 1]). A positive family history (parents, siblings) for a known etiology of myelopathy
was absent in this sample. However, up to 10% of patients presented with a family
history of stroke, 2.4% (n = 4) with monoparesis of unknown etiology, and less than
2% with family history of epilepsy, Parkinson’s disease, myasthenia gravis and X-linked
adrenoleukodystrophy. Parental consanguinity was present in only 3 cases.
Table 1
Group of medical comorbidities and prior clinical conditions presented by patients
in this study (n = 166). Only 7 patients (4,2%) did not show any significant past
medical history. Percentage among myelopathic patients are represented between brackets.
Relative frequency
|
Relevant past medical history
|
> 25%
|
Smoking (39.2%), hypertension (30.7%), alcoholism (26.5%).
|
10-25%
|
Prior malignancy (13.8%), hypercholesterolemia (13.2%), depression (11.5%), hypothyroidism
(10.2%).
|
5-10%
|
Chronic gastritis and hypertriglyceridemia (9.6%), urinary tract infection repeat
(8.4%), diabetes mellitus type 2 (7.8%), megaloblastic anemia (6.0%).
|
< 5%
|
4.8%: AIDS. 4.2%: Schistosomiasis, Helicobacter pylori infection, prior sexually transmitted
diseases. 3%: epilepsy, primary headache, deep vein thrombosis. 2.4%: Hepatitis C
vírus infection, prior pulmonary tuberculosis. 1.8%: abortions, morbid obesity, viral
poliomyelitis, prior stroke and acute myocardial infarction, hematologic malignancy,
cirrhosis. 1.2%: herpes zoster, parkinsonism, chronic atrial fibrillation, illicit
drug abuse, Chagas disease. 0.6%: chronic kidney disease on dialysis, renal tuberculosis,
optic neuritis, anterior uveitis, pulmonary thromboembolism, histiocytosis, diabetes
mellitus type 1.
|
The most frequent non-traumatic etiologies were subacute combined degeneration (11.4%),
cervical spondylotic myelopathy (9.6%), demyelinating disorders (9%), HTLV-related
tropical spastic paraparesis (8.4%), hereditary spastic paraparesis (4.8%) and schistosomal
myeloradiculopathy (3.6%) ([Table 2]). Undefined etiology represented 20.5% of cases. In cases of hereditary spastic
paraparesis, genetic testing for each subtype was routinely unvailable in our service,
regarding the diagnosis in familial patterns of neurological involvement and neuroimaging
findings. Paraneoplastic etiology was not evinced in our sample. Spondylotic cervical
myelopathy was the cause with higher average age of patients at diagnosis. Demyelinating
diseases, tropical spastic paraparesis and Chiari type I malformation presented the
profile of younger patients, as well as neuroschistosomiasis although some patients
discrepant.
Table 2
Main etiological groups of non-traumatic myelopathies, according to initial clinical
suspicion and to definitive diagnosis (n = 166). Percentage among myelopathic patients
are represented between brackets.
Etiological groups
|
Relative frequency
|
Initial clinical suspicion
|
Undefined (36.1%; n = 60), Compressive (21.1%; n = 35), Subacute combined degeneration
(vitamin B12 deficiency) (11.4%; n = 19), Demyelinating (9.0%; n = 15), Hereditary
spastic paraparesis (3.6%; n = 6), Chiari type I malformation, Schistosomal myeloradiculopathy,
Tropical spastic paraparesis (3.0%; n = 5), Postinfectious myelitis (2.4%; n = 4),
Adrenomyeloneuropathy, syringomyelia, Motor Neuron Disease (1.8%; n = 3). Others:
spinal cord malformations (1.2%; n = 2), HIV-associated vacuolar myelopathy (0.6%;
n = 1).
|
Definitive diagnosis
|
Undefined (20.5%; n = 34), Subacute combined degeneration (11.4%; n = 19), Cervical
canal stenosis with spondylotic myelopathy (9.6%; n = 16), Demyelinating (9%; n =
15) (Multiple Sclerosis 4,8%, Neuromyelitis optica 4.2%), Tropical spastic paraparesis
(8.4%; n = 14), Hereditary spastic paraparesis (4.8%; n = 8), Schistosomal myeloradiculopathy
(3.6%; n = 6), Spinal disk herniation (3.0%; n = 5), Chiari type I malformation, Vascular
myelopathy and Motor Neuron Disease (2.4%; n = 4). Others: various polyneuropathies
(4.8%; n = 8), isolated radiculopathy (3.6%; n = 6), movement disorder and syringomyelia
(1.8%; n = 3), Somatoform disorder and spinal cord tumours (1.2%; n = 2), Spinocerebellar
ataxia type 3, histiocytosis, Herpes zoster-related myelitis, actinic myeloradiculopathy,
Sarcoidosis, Copper deficiency myeloneuropathy, CMV-related myelitis, cervical retrolisthesis,
PSEN1-related myelopathy, Post-Polio syndrome, HIV-associated vacuolar myelopathy, Larsen
syndrome and Lumbar canal stenosis (0.6%; n = 1).
|
Regarding the functional clinical severity scale applied (European myelopathy score/EMS) and other myelopathy scores (Cooper myelopathy score, Prolo-Score, Nurick-Score), there was no correlation of greater or lesser severity and functional impairment
with specific etiologies ([Table 3]).
Table 3
Results from functional clinical severity scale and other myelopathy scores.
Scale used
|
Main results
|
EMS
|
48% score I (mild deficits), 19.3% score II (moderate deficits), < 5% score III (severe
deficits)
|
CMS (upper and lower limbs compromise)
|
3.6% with 7 to 8 points (maximum scores), 4.2% with zero score (minimum score), 70%
with scores 1 to 6 (60% with scores 1 to 3)
|
Nurick score (severity of functional impairment)
|
48% with scores 2 to 3 (moderate functional impairment), 26% with scores higher or
equal to 4 (severe)
|
Prolo score (economic and functional scale)
|
60% with grades II/III, 20.5% with grade I, 4.2% with normal values (grade 0)
|
EMS: European Myelopathy Score; CMS: Cooper Myelopathy Score.
Laboratory results and spinal fluid analysis
Serum evaluation was performed in all patients. Laboratorial serum screening disclosed
important results defining diagnosis of B12 vitamin deficiency, tropical spastic paraparesis,
adrenomyeloneuropathy and neuromyelitis optica ([Table 4]). There was a direct association of cases with high eosinophilic contents in the
cerebrospinal fluid and schistosomal myeloradiculopathy.
Table 4
Main serum and cerebrospinal fluid laboratory and neuroimaging results.
Additional tests
|
Main results
|
Serum laboratorial screening results
|
11.4% with cobalamin deficiency, 10.2% with high MCV, 9% with positive ANA, 4.2% with
positive HTLV-I/II serologic test, 4.2% with positive anti-aquaporin-4 antibodies,
< 2% with high VLCFA, 0.6% with copper deficiency
|
Cerebropinal fluid examination
|
3.6% with albuminocytologic dissociation, 3.6% with positive oligoclonal bands, 1.2%
with hypereosinophilic content (> 10% of total pleocytosis)
|
Neuroimaging findings
|
23.5% with non-compressive signal changes in any segments in T2/FLAIR images; 9.6%
of cases with cervical spine stenosis (16.9% of all cases with intervertebral disc
protrusions in the cervical segment)
|
Neurophysiological studies
|
1.8% with anterior horn cell compromise; 24.2% with demyelinating polyneuropathy;
5.4% with isolated axonal polyneuropathy; 3.6% with isolated radiculopathy
|
MCV: mean corpuscular volume; ANA: antinuclear antibody test; VLCFA: very long-chain
fatty-acids.
Neuroimaging and neurophysiological studies
Neuroimaging studies were routinely done in all patients with at least one cervical
and thoracic spine MRI, which in some cases was supplemented with cranial and lumbosacral
imaging. In 24% (n = 40) of cases, neuroimaging evaluation was unremarkable, and spinal
cord signal changes were seen in less than a half of cases (Table 4). Some case examples
are displayed in [Figure 1].
Figure 1 Some spinal cord MRI examples. (A) A 40-year-old man with a 8-month history of paraparesis,
upper and lower limbs paresthesias with no sphincter dysfunction and a sagittal MRI
section suggestive of Chiari type I malformation; (B) A 48-year-old man with a progressive
history of recurrent longitudinally extensive transverse myelitis and a sagittal MRI
section suggestive of a demyelinating disease with positive anti-aquaporin-4 antibody;
(C) A 68-year-old man with a 4-month history of shoulder muscles twitching and weakness
to lift objects with no sphincter dysfunction, and cervical spine MRI suggestive of
cervical spondylotic myelopathy; (D) A 52-year-old man with a 3-week-progressive paraparesis
with sagittal MRI section showing a pathological fracture of T10 vertebra originating
from an extensive pedicular mass and giving rise to a compressive thoracic myelopathy
from a neoplastic lesion (pathological diagnosis: plasmacytoma); (E) A 36-year-old
woman with exacerbation of chronic low back pain associated with urinary sphincter
dysfunction, paraparesis and hypoesthesia in the lower limbs, positive serological
tests for schistosomiasis and transverse MRI section showing a T10-T11 level hyperintensity
predominantly in dorsal roots, posterior column and lateral corticospinal tract, suggestive
of schistosomal myeloradiculopathy.
Electroneuromyography studies were performed in only 32% of cases, mainly in cases
with suspected motor neuron disease, radiculopathies and myeloneuropathies, independently
from the main suspicion causes in such cases. Normal results were observed in 14.5%
of cases. However, in less than 2% of cases defined the diagnosis of amyotrophic lateral
sclerosis and aided the definite diagnosis of isolated radiculopathies and polyneuropathies
(Table 4).
DISCUSSION
This study provides an interesting face of the main clinical, epidemiological and
neuroimaging findings of patients with non-traumatic myelopathies in our midst. Therefore,
our sample provides a relevant view on the most common causes of non-traumatic myelopathies.
In Cameroon, an underdeveloped country, non-traumatic myelopathies are more commonly
associated with compression, with 24.5% of cases accounting for neoplastic disease,
12.9% for spinal tuberculosis and 4.1% for cervical spondylotic myelopathy. Other
etiologies were such as for tropical spastic paraparesis (4.8%), 1.4% for HIV-related
vacuolar myelopathy (1.8%), and for multiple sclerosis and subacute combined degeneration
(0.7%) are rarely reported[9]. No etiology was found in 21.1% of cases. In our population we found higher prevalence
of vitamin B12 deficiency and demyelinating diseases.
Another large study was performed in Liverpool, England, in a 3-year-period with 585
patients with paraparesis or spastic quadriplegia, which revealed as major causes
of nontraumatic myelopathies cervical spondylotic myelopathy (23.6%), multiple sclerosis
(17.8%), extrinsic spinal cord neoplasia (16.4%) and motor neuron disease (4.1%)[10]. It has also shown that in 18.6% of cases no specific etiologies were found, even
after thorough etiologic investigation. In this study also the occurrence of neoplasms
was higher and the low prevalence of subacute combined degeneration. Interestly, the
percentage of patients with uknown etiology in both studies was very similar to our
results, unvealing the difficulties inherent in defining diagnosis of non-traumatic
spinal cord diseases. It is essential to disclose that our neurological service has
specific neurological units which also receive subspecialty cases and, thus, can explain
one of the reasons for a low prevalence of neoplastic (such as spinal cord tumors),
motor neuron disease (such as primary lateral sclerosis) and demyelinating disorders
(such as neuromyelitis optica and multiple sclerosis).
Other important contributions were obtained from our study: (i) in most cases of non-traumatic
myelopathy family history is of little relevance; (ii) structural causes, including
spondylotic cervical myelopathy, generally present with a longer symptom duration
period; (iii) double and severe sphincter compromise are highly suggestive signs of
schistosomiasis in our population; (iv) clinical severity of a myelopathy do not keep
a direct relation to a specific etiology; (v) all pure motor syndromes should be evaluated
with neurophysiological studies after a normal neuroimaging study to search for motor
neuron disease, even in the absence of bulbar symptoms at presentation; (vi) the youngest
patients were those with demyelinating diseases, tropical spastic paraparesis, Chiari
type I malformation and cases of neuroschistosomiasis without prominent pain complaints,
as well as cervical spondylotic myelopathy represents the main cause of non-traumatic
myelopathy in the elderly. Through these findings and the current literature, we developed
a complementary flowchart with a basic diagnostic algorithm for non-traumatic myelopathy
evaluation in our population ([Figure 2]).
Figure 2 Myelopathy algorithm. A proposed algorithm to evaluate nontraumatic myelopathies
and its main differential diagnosis.
This is a relevant study that describes the clinical and epidemiological profiles,
scales of severity and etiology of nontraumatic myelopathy, enabling the comparison
and understanding of spinal cord diseases in our clinical context, although the data
come from our reference service, not fully effectively representing population data.