Us and Mri Neurography Assessment of Diagnostic Criteria in Patients With Carpal Tunnel Syndrome Using Electrophysiological Tests as Gold Standard: A Prospective Study

Peripheral neuropathy evaluation depends mainly on physical examination, patient history, electrophysiological studies, with evoked potential abnormalities. High-resolution US has the advantage of being fast, non-invasive modality with nerve dynamic assessment allowing examination of long part of nerve. MR imaging serve better in examination of deeper nerves with higher contrast resolution. It shows great benet in patient with atypical presentation, Equivocal diagnosis and suspicious of secondary cause and post-surgical relapse. Methods This study was conducted prospectively on 32 patients, presented with carpal tunnel syndrome diagnosed by electrophysiological tests. Supercial US of the wrist joint was done to all participants followed by MRI within 1 weeks of the US. We aimed to assess the measurements & criteria of both US & MRN in diagnosis of CTS, depending mainly on the three-measurement assessed by Buchberger et al., then to nd the agreement between US & MR

that could not be elicited by US or equivocal cases for detection of secondary cause in clinically suspected patient.

Background
Neuropathy is a clinical term describing both sensory and motor abnormalities at areas supplied by speci c peripheral nerve, it may be caused by metabolic disorders or by regional structural disorders.
Carpal tunnel syndrome (CTS) represents the most common peripheral neuropathy of the upper extremities with Prevalence average 2 to 3% in the general population (1) Many risk factors were described as cause of CTS; the most common factor is Diabetes mellitus. Others include pregnancy (which can resolve after delivery), rheumatoid arthritis, obesity, acromegaly, hypothyroidism, metabolic depositional disease like gout, calcium pyrophosphate deposition, amyloidosis, and mucopolysaccharidosis (in children). CTS could also be induced by external compression as accessory muscles, tendons synovitis or wrist masses i.e., ganglion cyst, hamartoma, and lipoma or surrounding tissue masses (2) Nerve compression induces a cascade of pathophysiological changes mainly due to microcirculatory disorder. In early stages, compression will affect mainly the axonal transport which leads to symptomatic reversible damage. Later, the interstitial edema of the epineurium and endoneurium would cause consequent nerve damage starting with its sheath, giving recurrent symptoms) followed by damage of the axon which cause the denervation signs (muscle weakness and sensory abnormalities). At chronic stages, edema activates broblast and lead to brosis of supporting tissue. If CTS treatment fail, it should raise the possibility of Double crush syndrome, which states that if the nerve proximally compressed, its distal part is more liable to be compressed and vice versa (3) Peripheral neuropathy clinical evaluation depends mainly on physical examination, patient history & electrophysiological studies with evoked potential abnormalities (4). Conduction studies used mainly to diagnose the regional median nerve injury and the degree of nerve damage as well as both distal sensory nerve conduction velocities and motor latency abnormalities (5) High-resolution US has the advantage of being fast & non-invasive modality, added to this the nerve dynamic assessment with high spatial resolution and allowing examination of long part of nerve. Its main limitation is being operator dependent. (6) MR imaging serve better in examination of deeper nerves with higher contrast resolution. It shows great bene t in patient with atypical presentation, equivocal diagnosis, suspicious of secondary cause and post-surgical relapse. (7) 1-1. Ultrasonography diagnostic criteria: US is used in cases with normal electrophysiological tests with early disease stage (8). As, in early disease, the US nerve morphological changes precede its electrophysiological abnormalities. (2) Carpal tunnel syndrome US diagnostic features include: 1-Different caliber seen as proximal enlargement of median nerve followed by distal attening (Notch sign). Nerve constriction beneath exor retinaculum, giving hour glass appearance. In few cases distal nerve enlargement could be noted with limited nerve motion in sagittal plane [9] 2-Increased nerve CSA at pisiform and scaphoid level. Normal cross section ranges from 6.1 to 10.4 mm. Cross sectional area of 12mm² has 99% sensitivity, while 8.5-12 mm² showed 87% sensitivity in diagnosis of carpal tunnel syndrome with proportional relationship between increases CTA and nerve conduction velocity reduction (10). Patients with bi d nerves have cross sectional area of 12 mm2 calculated by adding the CSA of both its medial and lateral branches (11).

Methods
This study was conducted prospectively on 32 patients, presented with carpal tunnel syndrome diagnosed by electrophysiological tests, after approval of Ain Shams University Ethical Committee with Informed written consent taken from patients or guardians of patients who were invited to participate in the research.
The following exclusion criteria were utilized: 1-Patients with previous surgical intervention of the median nerves or wrist joint.
2-Patient with complaint of brachial plexus entrapment syndromes (to exclude high level entrapment) 3-Patients with contraindications for MRI e.g., an implanted pacemaker.

2-1 Imaging protocol:
Super cial US of the wrist joint was done to All participants by using super cial Ultrasonography set (Toshiba, Philips), high resolution probe of 7.5-10 MHz frequency. Patients were examined in seating position, with their face to the examiner showing extended arms and supinated forearm with examined the wrist on the table of examination. Both metacarpophalangeal and proximal interphalangeal joints mildly exed. Imaging both long and short axis of median nerve were taken using carpal bones as landmarks.
MRI was performed within 1 weeks of the US to ensure no interval change, using 1.5-Tesla [Achiva-Philips, Germany]. we used a phased array surface coil on the wrist region. Small Field of View (FOV) [5-10cm] was applied for high spatial resolution using the following sequences: 1-Axial T1 SE-weighted image [2-3mm] for anatomical baseline, and isotropic reconstruction. No contrast media is required except if super added in ammation was suspected.
2-attening index is calculated as a ratio between nerve transverse axis to its AP axis ( attening ratio) (D1/D2) should be less than 3.
3-Bowing index of exor retinaculum measured at the (hamate-trapezium level), a line is drawn connecting trapezium tubercle and hook of the hamate, then the distance from this line to most anterior part of transverse carpal ligament is calculated, Normally the distance is less than 4 mm. (bowing index means AP distance /transverse distance, it should not exceed 15%) 4-Nerve echo textural changes in US, and T2 signal intensity, fascicular pattern of the compressed median nerve in MRI was reported as well as the innervated muscles. The compressed nerve becomes uniformly hypoechoic in US and of high T2 signal in MRI with disrupted the fascicular pattern. The presence or absence of masses should be noted.

3-1 Statistical Analysis
The sex, age and the numbers of right and left wrists examined were tabulated.
The diagnostic agreement between US & MRI in patient with tunnel syndrome was tabulated by using CSA, Bowing and attening indices as well as nerve textural changes and identi ed underlying causes.
All statistical tests were performed with Spss (Statistical package for social science), version 20. Quantitative analysis was introduced as mean and standard deviation. Qualitative analysis was introduced as numbers and its related percentages. Chi square test was used to compare between qualitative variables.
One-way ANOVA was used to compare between more than two independent means. Pearson formulae was used to record quantitative variables relationship 3-2 Demographic data: A thirty-two CTS diagnosed patients with age ranging from 18.00-67.00 & 43.25 mean age, con rmed by Electrophysiological testing using Electromyography (EMG) and Nerve conduction velocity, were enrolled in our study. More than third of patients were suffering from mild CTS (34.4%), about third of patients were diagnosed as minimal neuropathy and quarter of them were diagnosed as moderate neuropathy.
Thenar Muscle wasting found in more than fourth of patients (28.1%). (Table 2) The participants were categorized as 20 out 32 females (62.5%) and 12 males. 26 of patients had right sided affection (81.2%) and 6 with left sided affection .16 of patients worked as housewives, 11 handworkers, 2 gymnast, 2 employee and one nurse. All the patients complained of wrist pain with 21 out of them complained of hand parathesis (65.6%) ( Table 1).
In our study, the majority of the patient showed no associated comorbidities (20 out of 32, 62.5%). In patients with co-morbidities, diabetes mellites was the commonest followed by rheumatoid arthritis. Two of our patients had wrist cut wounds (Table 1) MRI could detect underlying tunnel abnormalities in 15 patients. 8 of them with exors tenosynovitis, two had traumatic neuroma, three with ganglion cyst and two showed deep interstitial edema of carpal tunnel. (Table 5) (Figure 2)

3-5 Agreement study between MRI and US measurements:
Increased CSA in both MRI & US were was positive in 93.8% & 81.2% of patients respectively denoting higher US correlation compared to MRI with statistically signi cant nding (P value 0.02). (Table 6,7 & 8) Also, the increase in both bowing and attening indices were detected in 59.4% of patients for each using US compared to 56.2% of patients using MRI, denoting highly signi cant statistical variability (p value 0.001). ( Underlying local causes were detected at 31.25% of patients by US compared to 46.8%of cases using MRI. Two patients of tenosynovitis and 3 patients with ganglion cysts were missed sonographically, denoting highly statistically signi cant nding (p value 0.001) ( Table 9).

Discussion
The term "Entrapment syndrome" is used to describe neuropathic changes due to local structural abnormality or intrinsic nerve lesions (13). Electrophysiological testing and clinical examinations are the corner stones in diagnosis of CTS and can be used as gold slandered to detect e cacy and sensitivity of other diagnostic modalities (14) In our study all included patients were diagnosed based on clinical signs con rmed with electrodiagnostic examinations. US used as noninvasive modality for assessment of nerve entrapment with advantage of real time, high resolution, low cost and dynamic imaging, yet drawbacks were being operator dependent and sometimes di cult if images degraded by shadowing and tissue distortion as in cases of scarring and local injury (15). The compression of median nerve at carpal tunnel leads to consequent attening of nerve with swelling of its proximal part, causing endo-neural edema. This was the reason for using the CSA as measurement for diagnosis of CTS, yet later on, other measurements were added by Buchberger et al., which include attening ratio and bowing index. (19) In our study, we aimed to assess In previous studies, the CSA cut off value ranged from 6.1 to10.4 mm2 with such 4.3mm2 difference of both normal values (4.3mm2) represent 51% of normal CSA of median nerve (8.4 mm2) (16). Yesildag et al., 2004 (23) concluded that US measurements of median nerve CSA was the most predictive measurement for CTS with cut off value 10.5mm2 at proximal tunnel level, providing a diagnostic sensitivity and speci city of 89% and 94.7% respectively. Compared to Buchberger et al., who mentioned that the mean CSA of 14.5 mm2 in CTS patients and 7.9 mm2 in control group, and Duncan et al., that reported that the mean CSA in CTS patients and the control group to be 12.7 mm2 and 7 mm2, respectively. Such results variability may be attributed to different study design measurement techniques or due to exclusion of patient with mild electrodiagnostic test Buchberger.,et al (20) recorded the mean median nerve CSA at proximal tunnel 14.5mm2(range,8.8-20.5mm2; SD,3.8mm2). The mean attening ratio was 2.7 range, 2.0-3.7; SD, 0.4) at pisiform bone. The exor retinaculum bowing (mean 3.7mm; range, 2.0-6.0mm; SD, 1.1mm). So, our study showed that all patient diagnosed by CTS fall in the same range described by Buchberger with mean CSA 14.96 mm2 +/-4.2 ranging (4 -24 mm2), Mean Bowing index was 15.11 +/-4.42_ ranging (8.32 -27.00) and mean Flattening ratio was 2.97+/-0.69 and ranged 1.54 -4.20. Bowing index even showed higher value in our study as most of our patients were diabetic with high percentage of them showed tenosynovitis, tunnel interstitial edema and tissue swelling.
Sonographically, we found that using CSA was the most frequently occurring parameter, as it was positive in 93.7% of our patients, followed by decrease nerve echo texture (90.6%). Unfortunately, there is no studies in literature to evaluate the diagnostic capability of retinacular bowing index and attening index of median nerve as separate diagnostic parameters in CTS, however at our study they were recorded positive in 59.4% for each in US, denoting relatively low predictive value compared to the CSA and nerve echotexture changes Magnetic resonance Neurography is an excellent modality for soft tissue contrast, allowing detection of subtle abnormalities as T2 increased signal within nerve bers and fascicular pattern. Yet, isolated magnetic resonance sign of nerve high T2 signal showed speci city less than 40%. Therefore, using additional MRN signs and parameters of neuropathy, i.e enlarged nerve (> 10-11 mm2) proximal to the tunnel and at the level of pisiform bone, nerve attening at the level of the hook of the hamate at the distal tunnel and retinaculum palmar bowing add to MRN speci city in detection of CTS. Effaced carpal tunnel fat and thenar muscle denervational edema may be seen as secondary ndings of compressed median nerve (16). Pasternak., et al proved that MRI as diagnostic tool using increased T2-signal, CSA, distal nerve attening & retinaculum bowing were the most frequently occurring signs in CTS. our study showed that occurrence of these parameters was 90.6%, 81.2%, 56.2%& 56.2 respectively. Kim et al, 2011 reached to a conclusion that MRI was more sensitive in detection of muscle denervation changes in form of high signal intensity. These changes progress from acute (edema-like T2 signal intensity), sub-acute (muscle edema with early fatty changes and /or atrophy) to chronic (muscle atrophy and fatty changes). Add to it characterization of space occupying lesions, brotic changes or thickened fascia. We agreed with Kim et al, and concluded that US was able to diagnose muscle denervation changes in two cases only, while MRN was able to detect muscle denervation changes in 34.4% of patients, and underlying tunnel abnormalities in 15 patients out of 32, which prove the higher sensitivity of MRN in detection of secondary muscle changes of CTS. (Case 2) In our study we tabulated agreement between MRI & US regarding the three main parameters CSA, bowing and attening indices and we reached to a result that US was better in detection of CTS using the three parameters with high signi cant statistical variability (p value 0.001).
The US was able to detect cause of the entrapment in about 31.2% of the cases and about 68.8% of the cases are considered of idiopathic cause, while MRN was able to detect cause of the entrapment in about 46.9% of the cases and about 53.1% of them are considered of idiopathic cause. Also noted the ability of MRI in diagnosis of muscle denervation changes as secondary sequel of nerve entrapment (Case 3). So, in the cases at which primary nerve abnormality could not be visualized by US, the detection of innervated muscle MRI signal changes could be used to diagnose and locate the nerve lesion, denoting higher sensitivity of MRN in detection of secondary causes and muscle denervation changes with highly statistically signi cant difference.
Our results agree with Martinoli et al., who found that US results was comparable to MRN in diagnosis of CTS. Yet, MRI was superior to US in recognizing subtle changes, as neural signal changes caused by edema and blood perfusion changes. Also, we agreed with Thawait K., et al (25) who proved that MRN could support the clinical data, giving information about the nature of the underlying nerve lesion, de ning its site and extent, with better intra-neural fascicular pattern assessment, and providing an overview of surrounding oft tissue and regional muscle abnormalities.

Conclusion
We could conclude that ultrasound examination can be used as rst imaging step after physician evaluation with comparable results to electrophysiological studies in evaluating CTS and try to nd the cause. MRN examination came as second step in patients with suspected muscle denervation changes that could not be elicited by US or equivocal cases for detection of secondary cause in clinically suspected patient. 6  Causes of Carpal tunnel syndrome by MRI

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