Superimposed Carpal Tunnel Syndrome in a Patient with Charcot-Marie-Tooth Disease Type 1A: Case Report and Diagnostic Considerations

Abstract

Introduction

We present a case of Charcot-Marie-Tooth disease type 1A (CMT1A) complicated by symptoms concerning for superimposed carpal tunnel syndrome (CTS). Diagnostic interpretation was challenging due to overlapping electrodiagnostic and ultrasound findings typical of CMT1A.

Case Presentation

A 54-year-old woman with genetically confirmed CMT1A reported bilateral intermittent burning, numbness, and tingling in digits 1–3, worse at night and with hand use. Physical exam revealed positive Tinel’s and Phalen’s signs bilaterally with preserved motor strength and no thenar atrophy. Electrodiagnostic studies showed diffuse demyelinating polyneuropathy, consistent with CMT1A, with slowed conduction velocities in all nerves tested and prolonged sensory peak latencies in both median and ulnar nerves. Neuromuscular ultrasound revealed diffuse nerve enlargement consistent with hereditary neuropathy. However, focal enlargement of the median nerves at the carpal tunnel – 13 mm² on the right and 12 mm² on the left – yielded elevated wrist-to-forearm ratios of 1.44 and 1.75, respectively, suggestive of superimposed CTS. Ultrasound-guided corticosteroid injection served both diagnostic and therapeutic purposes, bridging the patient to appropriate definitive management with carpal tunnel release and ultimately an excellent clinical outcome.

Conclusion

CTS and CMT1A share overlapping clinical and diagnostic features which complicates the recognition of a superimposed entrapment neuropathy. In patients with hereditary neuropathies, new focal symptoms should prompt consideration of superimposed compressive or entrapment neuropathies. In this case, the multimodal approach which entailed electrodiagnostics, ultrasound, and a therapeutic response to corticosteroid injection enabled accurate identification and effective treatment.

Introduction

Charcot-Marie-Tooth disease is the most common inherited peripheral neuropathy that affects upward of 1 in 2,500 individuals [1]. The most prevalent subtype, Charcot-Marie-Tooth disease type 1A (CMT1A), is a symmetric demyelinating polyneuropathy inherited in an autosomal dominant pattern. It is caused by a duplication – or less commonly, a point mutation – of the PMP22 gene located on chromosome 17p11.2 [2, 3]. Overexpression of peripheral myelin protein 22, which is essential for synthesis and maintenance of the myelin sheath in the peripheral nervous system, leads to gradual symptom onset in adolescence or early adulthood. Typical clinical features include progressive sensorimotor neuropathy, distal muscle atrophy, pes cavus with hammertoes, and balance difficulties [4].

Individuals with CMT1A disease may additionally suffer from acquired entrapment neuropathies such as carpal tunnel syndrome (CTS). While CTS affects approximately 3–6% of the general adult population, studies suggest a higher prevalence of up to 11.5% among individuals with CMT1A [5]. A thorough clinical history and concordant examination findings, particularly sensory loss in the median nerve distribution in the absence of comparable ulnar sensory deficit, support a diagnosis of CTS. Intermittent hand numbness with use and upon waking is characteristic of CTS. Provocative testing such as Phalen’s and Tinel’s may aid in clinical evaluation, and electrodiagnostic studies can further support the diagnosis and help exclude alternative etiologies [6]. However, standard electrodiagnostic criteria for CTS may be confounded by the underlying demyelination, slowed conduction velocities, and reduced median nerve motor amplitudes inherent to CMT1A [6, 7]. This case illustrates how an ultrasound (US)-guided corticosteroid injection can provide both diagnostic clarity and therapeutic benefit for a patient with hereditary polyneuropathy and superimposed entrapment neuropathy. This case report was prepared in accordance with the CARE Checklist (online suppl. material; for all online suppl. material, see https://doi.org/10.1159/000553624).

Case Description

History and Physical Exam

A 54-year-old woman with confirmed genetic diagnosis of CMT1A presented to a neuromuscular clinic with intermittent burning pain, numbness, and tingling in digits 1–3, primarily affecting the thumbs and more pronounced on the right side. Her symptoms were worse at night and during activities such as typing. She had trialed hand braces with partial relief. The patient also reported chronic neuropathy in both feet, balance difficulties, and high arches, consistent with her underlying CMT1A. On physical examination, she demonstrated full range of motion at the elbows, forearms, wrists, and hands, with preserved finger extension bilaterally. Tinel’s sign was positive over the distal median nerve at the wrists, and Phalen’s maneuver reproduced her symptoms bilaterally. Sensory testing revealed altered sensation in the median nerve distribution in the upper extremities and decreased sensation to light touch circumferentially in the lower extremities. Function of the abductor pollicis brevis was intact bilaterally, and there was no significant thenar muscle atrophy. There was pes cavus and hammertoe deformities in the lower extremities, but no clear intrinsic wasting in the upper extremities. Given the overlap of symptoms between her known hereditary neuropathy and those of CTS, the clinical challenge lies in determining whether her symptoms were attributable solely to CMT1A, or if a superimposed entrapment neuropathy was present.

Diagnostic Results

A nerve conduction study (NCS) and electromyography previously conducted at an outside facility were consistent with a generalized demyelinating sensorimotor peripheral neuropathy. On subsequent presentation to the neuromuscular clinic, US was utilized to further evaluate the patient’s current symptoms. NCS revealed diffusely slowed conduction velocities of the bilateral median, ulnar, tibial, and peroneal nerves. Specifically, both the median and ulnar sensory NCS showed prolonged peak latency bilaterally (right median 5.7, ulnar 4.6; left median 4.58, ulnar 5.02). There was preferential prolongation of the median motor responses compared with the ulnar motor responses. These findings are consistent with demyelinating sensorimotor neuropathy. Complete NCS results are outlined in Tables 1 and 2.

Table 1.

Sensory NCSs reveal diffuse slowing and mild axonal loss

Sensory nerve conduction	Recording site	Onset latency, ms	Peak latency, ms	Amplitude, µV	Segments	Distance, cm	Onset velocity, m/s
L median, ulnar – D1, D2, D3, D5, palm
Median wrist	Digit I (thumb)	3.75	4.63	9.3	Median wrist – digit I (thumb)	9	24.0
Median wrist	Digit II (index)	3.81	4.58	7.4	Median wrist – digit II (index)	13	34.1
Median wrist	Palm	1.56	2.67	35.0	Median wrist – palm	6	38.4
Ulnar wrist	Digit V (little)	4.06	5.02	6.7	Ulnar wrist – digit V (little)	10	24.6
L sural – ankle (calf)
Calf	Ankle	3.17	4.38	11.7	Calf – ankle	14	44.2
R sural – ankle (calf)
Calf	Ankle	3.46	4.40	8.0	Calf – ankle	14	40.5
R median, ulnar – D1, D2, D3, D5, palm
Median wrist	Digit I (thumb)	4.31	4.94	7.5	Median wrist – digit I (thumb)	9	20.9
Median wrist	Digit II (index)	4.77	5.73	6.0	Median wrist – digit II (index)	13	27.2
Median wrist	Palm	1.85	2.88	39.4	Median wrist – palm	7	37.8
Ulnar wrist	Digit V (little)	3.96	4.60	6.3	Ulnar wrist – digit V (little)	10	25.3

Table 2.

Motor NCSs reveal diffuse slowing and secondary axonal loss

Nerve/sites	Muscle	Latency, ms	Amplitude, mV	Segments	Distance, cm	Latency difference, ms	Velocity, m/s
L median – APB
Wrist	APB	6.46	3.2	Wrist – APB	7	-	-
Elbow	APB	15.06	4.5	Elbow – wrist	23	8.60	26.7
L ulnar – ADM
Wrist	ADM	4.71	5.6	Wrist – ADM	7	-	-
B. elbow	ADM	10.54	3.5	B. elbow – wrist	21	5.83	36.0
A. elbow	ADM	13.21	3.3	A. elbow – B. elbow	10	2.67	37.5
L peroneal – EDB
Ankle	EDB	7.60	0.2	Ankle – EDB	8	-	-
Fib head	EDB	20.50	0.3	Fib head – ankle	31	12.90	24.0
L tibial – AH
Ankle	AH	6.02	1.3	Ankle – AH	8	-	-
Pop fossa	AH	20.04	0.4	Pop fossa – ankle	36	14.02	25.7
R peroneal – EDB
Ankle	EDB	7.58	0.2	Ankle – EDB	8	-	-
Fib head	EDB	21.29	0.2	Fib head – ankle	30	13.71	21.9
R tibial – AH
Ankle	EDB	6.94	2.2	Ankle – AH	8	-	-
Pop fossa	EDB	25.23	0.7	Pop fossa – ankle	35	18.29	19.1
R median – APB
Wrist	APB	7.38	2.7	Wrist – APB	7	-	-
Elbow	APB	14.79	2.3	Elbow – wrist	23	7.42	31.0
R ulnar – ADM
Wrist	ADM	4.42	6.9	Wrist – ADM	7	-	-
B. elbow	ADM	10.17	6.7	B. elbow – Wrist	21	5.75	36.5
A. elbow	ADM	13.56	5.9	A. elbow – B. elbow	11	3.40	32.4

APB, abductor pollicis brevis; ADM, abductor digiti minimi; EDB, extensor digitorum brevis; AH, abductor hallucis.

Neuromuscular US revealed symmetric nerve enlargement in all extremities tested (shown in Fig. 1). There was uniform enlargement of the bilateral median and ulnar nerves, consistent with a demyelinating hereditary neuropathy. Focal median nerve enlargement was noted at the wrists – 13 mm² on the right and 12 mm² on the left (normal <12 mm²) – compared to the forearm measurements of 9 mm² (right) and 8 mm² (left). The resulting wrist-to-forearm ratios were elevated at 1.44 on the right and 1.75 on the left (normal <1.4). The median nerves were enlarged proximally at the elbows and axilla, typical of CMT1A. Although these findings were suggestive of CTS, this was difficult to definitively interpret in the setting of CMT1A.

Fig. 1.

US images. a Left median nerve at the wrist enlarged to 14 mm² with normal echogenicity and normal fascicular architecture. Dynamic evaluation showed normal mobility of the median nerve at the carpal tunnel. b Right median nerve at the wrist enlarged to 13 mm² with normal echogenicity and normal fascicular architecture. Dynamic evaluation showed normal mobility of the median nerve at the carpal tunnel. c Left median nerve at elbow enlarged to 12–13 mm² with uniform enlargement of fascicles. d Left median nerve at axilla enlarged to 11 mm² with uniform enlargement of fascicles. e Left ulnar nerve at cubital tunnel with mild enlargement to 10 mm² with normal echogenicity and normal fascicular architecture. f Left ulnar nerve in upper arm diffusely enlarged to 14 mm² with normal echogenicity, and normal fascicular architecture.

Management and Outcome

The patient underwent diagnostic and therapeutic bilateral US-guided, one-time, standard-strength corticosteroid injections performed by a neuromuscular physiatrist. Following the procedure, the patient maintained full range of motion in the hands and wrists and subjectively reported 70% relief of paresthesias in the median nerve distribution. Given the favorable response, she was referred to hand surgery for definitive management. The patient subsequently underwent bilateral carpal tunnel releases. Postoperatively, she reported 100% resolution of her paresthesias and pain including during activities such as typing. To this day, she remains highly satisfied with her treatment outcome and has experienced no adverse or unanticipated complications.

Discussion

This case highlights a patient with a known history of CMT1A who presented with intermittent paresthesias and positive Tinel’s sign and Phalen’s test, raising concern for superimposed CTS. The underlying demyelination, slowing, and reduced median nerve motor amplitudes in CMT1A can obfuscate the diagnosis of CTS based on standard electrodiagnostic criteria [6, 7]. Moreover, patients with CMT1A often have diffuse cross-sectional enlargement of the median nerve on US [8], which is a hallmark finding in CTS. Thus, the electrodiagnostic studies and ultrasonography commonly used to assess CTS overlap with the characteristic findings in CMT1A, obscuring the distinction and complicating the diagnosis of a new-onset entrapment neuropathy [9].

Providing some clarity on this diagnostic challenge, one case study noted that disproportionate enlargement of the median nerve at the carpal tunnel inlet and/or outlet, accompanied by relative narrowing within the tunnel, may suggest superimposed CTS in patients with CMT1A [10]. That study also described the diagnostic value of nerve US in CMT1A patients with suspected CTS, including examination of pre- and postoperative US findings following carpal tunnel release. However, interpretation of peripheral nerve US findings in CMT1A remains challenging, particularly given the limited availability of disease-specific normative cross-sectional area (CSA) data. Prior studies have demonstrated that CSA enlargement in CMT1A may exceed twice that observed in healthy controls [11]. Nevertheless, there are no established CSA thresholds that reliably distinguish hereditary neuropathic enlargement from superimposed compressive neuropathy. In the present case, the CSAs of the median nerves were not dramatically elevated, which underscores the difficulty of relying on absolute CSA measurements alone. Furthermore, baseline US assessment is not currently standard practice in patients with confirmed hereditary neuropathies, making it difficult to evaluate interval CSA changes if and when CTS symptoms develop. Prospective acquisition of baseline nerve US measurements may prove valuable in the future, as longitudinal or patient-specific comparisons may aid in identifying focal interval enlargement that suggests an entrapment neuropathy. In contrast, our report focuses on the clinical utility of an US-guided corticosteroid injection as both a diagnostic and therapeutic adjunct. In our patient’s case, a favorable response to injection supported the presence of a compressive neuropathy and helped guide subsequent definitive surgical decompression.

Additional sensitive electrodiagnostic techniques may have been pursued to evaluate suspected CTS. These include the Combined Sensory Index (CSI) which includes the (1) median-radial sensory latency difference in digit 1, sensitivity 85–94% [12, 13], (2) the median-ulnar sensory latency difference in digit 4, sensitivity 85–98.1% [13, 14], and the (3) median-ulnar trans carpal orthodromic comparison study (“mid-palm study”) [15]. Another study further demonstrated that mid-palm studies identified an additional 15.3% of CTS cases among patients with normal findings on standard electrodiagnostic testing [16]. However, there remains limited evidence regarding the diagnostic performance of these techniques specifically in patients with concomitant CMT and CTS, in whom baseline diffuse demyelinating abnormalities may complicate interpretation. In a similar vein, the utility of side-to-side median latency comparisons in patients with CMT1A may be limited by the presence of bilateral, diffuse demyelinating abnormalities that can reduce inter-limb electrophysiologic differences. Consequently, there may be greater utility in within-nerve comparisons among patients with bilateral CTS or systemic polyneuropathies.

Other electrodiagnostic techniques have been described for the evaluation of CTS in patients whose underlying medical conditions complicate the clinical neuropathy picture, although these approaches are primarily utilized in the setting of sensory axonal length-dependent neuropathies. One study among a heterogenous patient population noted the short-segment (“inching”) study across the wrist to yield a sensitivity of 86.3% in diagnosing CTS [17], while a study in patients with diabetic polyneuropathy and CTS symptoms noted an increased sensitivity of 95.7% [18]. Another posited CTS diagnostic is assessment of the second lumbrical-interosseous latency difference, which has been found to have a sensitivity of 76% in a heterogenous symptomatic population [19] and a comparable sensitivity of 73.9% in symptomatic patients with underlying diabetic polyneuropathy [18]. While these methods may serve to help localize focal median nerve conduction slowing across the carpal tunnel when standard electrodiagnostic findings are difficult to interpret, the diagnostic performance of these techniques specifically in patients with CMT1A remains incompletely characterized. Although these adjunctive electrodiagnostic studies were not performed in the present case, future investigations may help clarify their utility in distinguishing superimposed compressive neuropathy from a primarily uniform demyelinating neuropathy.

Heightened clinical suspicion of superimposed CTS in patients with CMT1A is justified given the pathophysiology. The nerve hypertrophy inherent to CMT1A not only complicates diagnostic interpretation but may also predispose the median nerve to compression within the narrow carpal tunnel space, thereby increasing the risk of CTS. Indeed, studies suggest that the prevalence of CTS in individuals with CMT1A may be as high as 11.5%, compared with 3–6% in the general adult population [7]. However, caution must be exercised in arriving at this diagnosis. One study remarks that the diffuse nerve enlargement on US in patients with CMT1A is an equivocal finding and cautioned against making surgical decisions based on US findings alone [5]. Another group has recommended the 11-point CTS Symptom Severity Score (SSS) as a useful clinical tool that provides a standardized method for evaluating CTS symptoms in patients with underlying inherited neuropathy. The SSS has also been used to monitor response to interventions such as splint therapy or surgical decompression [7]. However, the incremental diagnostic value of this questionnaire when used alongside imaging modalities such as US has not yet been quantified.

A key strength in this case study is the multimodal diagnostic approach which integrated standard provocative clinical testing, NCSs, nerve US, and injection. Some limitations include the restricted generalizability of a single case and a lack of standardized outcome measures apart from subjective patient report. Additionally, while an important addition to the arsenal of diagnostic tools, the injection response alone cannot be considered independently diagnostic of compressive neuropathy.

In this clinical case, a favorable response to the corticosteroid injection was used to support the diagnosis of CTS and informed subsequent management, including surgical carpal tunnel release – an intervention that ultimately led to significant and sustained symptom improvement. Overall, this case highlights the value of a comprehensive, multimodal approach and formally introduces the concept of a diagnostic corticosteroid injection when evaluating new neurologic symptoms in patients with underlying neuromuscular disease.

Statement of Ethics

The University of Texas Southwestern Institutional Review Board (IRB) approved this project as nonregulated research. The IRB number is STU20260061. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

H.C. contributed to the conceptualization, design, data acquisition, interpretation, and critical revision of the manuscript, and gave final approval. K.S. contributed to the investigation, data acquisition, interpretation, drafting of the manuscript, and critical revision of the manuscript, and gave final approval.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

All data generated or analyzed during this study are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.