Case Report: Absent F-Waves in a Case of Spinal Ischemia – A Potential Source of Diagnostic Error

Abstract

Introduction

Rapidly progressive para- or tetraparesis and early loss of F-waves on electrodiagnostic studies usually indicate acute inflammatory demyelinating polyneuropathy. A less common alternative etiology is acute spinal cord pathology.

Case Presentation

We describe here a case of a 65-year-old woman with progressive motor deficits and absent F-waves early in the disease course due to anterior spinal artery syndrome. We provide serial electrodiagnostic findings with a focus on the basic electrodiagnostic parameters as well as imaging correlates during the inpatient management.

Conclusion

Anterior spinal artery syndrome represents an uncommon cause of absent F-waves on the electrodiagnostic exam. Absent F-waves may precede any changes on the imaging and follow-up investigations are often warranted, as spinal cord ischemia can be a dynamic process.

Introduction

Analysis of F-wave responses is a widely used tool in electrodiagnostic studies (EDX) to assess the integrity of proximal parts of peripheral motor nerves, the name deriving from the first recording in foot muscles by Magladery and McDougal in 1950 [1, 2]. As late motor responses, they are believed to be generated by antidromic activation of spinal anterior horn cells, with the backfired compound muscle action potential (CMAP) being visible with a latency of 25–32 ms in upper extremity motor nerves and 45–56 ms in lower extremity motor nerves [3, 4]. The absence of F-waves on EDX is an early and well-known finding in Guillain-Barré syndrome (GBS) and often precedes any detectable change in the cerebrospinal fluid (CSF) parameters [5, 6].

Absent or severely prolonged F-waves outside of inflammatory demyelinating neuropathies have also been described in hyponatremia [7], neuroborreliosis [8], spinal cord infarction [9, 10], acute transverse myelitis [11], or spinal cord traumatic injury [12, 13]. We here present a case in which absent F-waves on the EDX preceded the visualization of spinal ischemia on magnetic resonance imaging (MRI).

Case Report

A 65-year-old woman with no relevant medical history presented to the emergency room of an external hospital with thoracic back pain of sudden onset and concomitant radiation into the shoulder girdle. Emergency workup excluded an aortic dissection, pulmonary embolism, and myocardial infarction. Over the next few hours, a distal paraparesis developed, worsening the next day, and leading to gait disturbance accompanied by urinary incontinence.

The clinical examination on day 2 after symptom onset showed distal paraparesis, brisk tendon reflexes in the upper extremities, reduced patellar, and absent Achilles tendon reflexes, as well as ataxic gait. CSF analysis on days 1 and 3 revealed normal cell count, cytology, and protein concentration. MRI of the brain and cervical spine on day 2 was read as unremarkable. EDX on day 3 showed reduced motor amplitudes of the left median and ulnar nerves, and both peroneal and tibial nerves. A partial conduction block was demonstrated in the upper arm portion of the right median nerve, without further signs of demyelination on the EDX. F-waves were absent in the left median and ulnar nerves. No sensory nerve action potentials (SNAPs) were obtained in the left median, left radial, and right sural nerves. In this clinical setting, the suspicion of an early-stage GBS on top of a preexisting sensory-motor polyneuropathy was raised. Despite the absence of an albuminocytological dissociation on serial CSF analyses, the findings were deemed compatible with the early course of the disease.

The paraparesis progressively worsened 3 days after the symptom onset, leading to a tetraparesis with worsening of arm strength by the hour. In the face of this dramatic development, therapy with intravenous immunoglobulins was initiated, and upon further deterioration, the patient was referred to our institution for plasmapheresis. Repeated MRI of the cervical and thoracic spine later revealed a ventral myelopathy signal as well as contrast enhancement of the lower cervical and upper thoracic spinal cord (Fig. 1b). Retrospectively, the thoracic myelopathy could be identified as well on the imaging the day before (Fig. 1a). An extensive neuroinflammatory and neuroinfectious workup was negative.

Fig. 1.

Acute progressive myelopathy in the cervicothoracic spine. MR images of the patient’s spine from the initial examination on day 2 and follow-ups on days 3 and 9. a1, a2 T2w hyperintensity in the ventral spinal cord from TH1 to TH2. b1, b2 Discrete bilateral gadolinium-enhancement and slight progression of the T2w hyperintensities (not shown). c1, c2 Further progression of now extensive T2w-hyperintense lesions in the spinal cord from C4 to TH4.

We repeated the EDX on day 5, demonstrating normal amplitudes in the motor studies of the median, ulnar, peroneal, and tibial nerves on both sides (Fig. 2). SNAPs of the upper (median and ulnar nerves) and lower (sural nerves) extremities were normal. Apart from a focal slowing in the left ulnar nerve between the below- and above-elbow stimulation, indicating an ulnar sulcus syndrome, there were no signs of demyelination. We could not reproduce the conduction block in the right median nerve. However, except for the left tibial nerve, F-waves were absent throughout.

Fig. 2.

The serial EDX findings. The serial EDX showed intact sensory potentials of the upper and lower limbs (a, sural nerve bilaterally shown), initially normal CMAP amplitudes on day 5 after symptom onset (b, scale amplitude: 5 mV), with absent F-waves in the upper extremities and intact F-waves of the left tibial nerve (c). There was a significant reduction of the CMAP in the upper extremities without any change in the lower extremities (not shown) on day 15 after symptom onset (d, scale amplitude: 1 mV). CMAP, compound muscle action potential; EDX, electrodiagnostic studies.

Upon our follow-up clinical examination, muscle tendon reflexes were brisk in all extremities, and the Babinski sign had turned positive bilaterally. There was reduced sensation for warm/cold stimuli as well as pinprick, whereas vibration sensation and position sense were normal, indicating an intact posterior column. Ultimately, an anterior spinal artery syndrome of the cervical spine was diagnosed.

The MRI on day 9 showed further progression of now extensive T2w-hyperintense lesions in the spinal cord from C4 to TH4 (Fig. 1c). The consecutive standardized stroke-workup (transthoracic echocardiography, 48-hour-electrocardiogram, duplex sonography of the cervical arteries showing unremarkable, equally sized vertebral arteries, CT-angiography of the aorta, including further workup of the CSF) could not identify a clear etiology or an underlying vascular pathology, leaving the cause of the spinal cord ischemia elusive. Antithrombotic as well as lipid-lowering therapy was established according to guidelines.

We repeated the EDX on day 15 after symptom onset. The amplitudes of CMAP of the median and ulnar nerves were significantly reduced bilaterally with no signs of demyelination. The F-waves remained absent (Fig. 2). There was no significant difference in the CMAP amplitudes of both the tibial and peroneal nerves. The tibial F-waves were now obtained bilaterally with normal latencies, making the initially absent right tibial F-wave on the first EDX at our institution a technical issue, possibly due to peripheral inactivity edema. In light of the clinical aspects, the unrevealing spinal taps and the imaging, we concluded that the EDX studies were compatible with an anterior horn cell pathology in the cervical spine. The electrophysiological findings over time are summarized in Table 1.

Table 1.

EDX findings during spinal cord ischemia

​	CMAP (mV)	DML (ms)	NCV (m/s)	SNAP (μV)	F-wave (ms)
Acute stage	=	=	=	=	–/↑
Later stages	–/↓	=	=	=	–/↑

↑ indicates prolongation of F-wave latency; ↓ indicates reduction of CMAP amplitude; = indicates no change. Relevant findings are highlighted in bold.

CMAP, compound muscle action potential; DML, distal motor latency; NCV, nerve conduction velocity; SNAP, sensory nerve action potential.

Discussion

We demonstrate early absent F-waves in a case of acute spinal cord ischemia with anterior spinal artery syndrome. The EDX pattern with the initially negative MRI of the cervical spine was misleading, further emphasizing the non-specificity of absent F-waves in this setting. The rapid onset of predominant motor syndrome, external EDX with the finding of absent F-waves, and further signs of a possible acute inflammatory demyelinating polyneuropathy (initial diagnosis of a conduction block in the right median nerve) lead to the treatment with intravenous immunoglobulins, with therapy escalation to PEX later on. There was, however, no subjective or objective clinical improvement following this treatment. The reduced amplitudes of the sensory and motor nerves on the initial EDX gave the impression of a preexisting polyneuropathy. We failed to identify any relevant preexisting polyneuropathy on the EDX on day 5 at our institution. The initial findings of reduced motor and sensory action potentials could have been results of an inactivity edema. The clinical reexamination, the serial EDX (reduction of CMAP amplitudes in the cervical segments with no change of CMAP amplitudes in the lumbo-sacral segments and no change in SNAPs) and the spinal cord imaging were compatible with an anterior spinal artery syndrome. The absent F-waves in this case were pointing towards an impaired motoneuron integrity in the anterior horns in the cervical spine. The successive reduction of CMAPs indicates Wallerian degeneration.

The electrophysiologic presentation in the upper extremity motor nerves could, theoretically, point toward a “pure motor” axonal variant of GBS (acute motor axonal polyneuropathy). However, this variant is relatively uncommon in Western Europe [14], and the clinical picture and time course of symptoms in our case argue against this pathology. Single reports have used the reemergence of F-waves as a possible prognostic marker in cases of spinal ischemia [15]. However, its reliability has not yet been validated.

Conclusion

This case report illustrates the importance of adding anterior spinal artery syndrome to the differential diagnosis of absent F-waves on the EDX, as these point not only towards acquired demyelinating neuropathies but also disturbed motoneuron integrity in the setting of anterior spinal cord disease, and may precede any changes on the spinal cord imaging. Although EDX studies are not routinely incorporated into the diagnostic algorithm for spinal cord ischemia, they may, in certain cases, provide valuable information that further guides the diagnostic and therapeutic process.

Statement of Ethics

The authors confirm that the approval of an Institutional Review Board was not required for this work. This retrospective review of patient data did not require ethical approval in accordance with local guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000550477).

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This work was not supported by any sponsor or funder.

Author Contributions

E.T.A.B. and M.V.B.: medical care and recruitment of the patient, review of literature, and drafting and review of the manuscript. M.M., M.W., and H.H.J.: medical care of the patient and review of the manuscript. N.N.: interpretation of the imaging and drafting and review of the manuscript. Z.K.: interpretation of supervision of the imaging, medical management of the patient, and review of the manuscript. A.B.: medical care of the patient and drafting and review of the manuscript.

Funding Statement

This work was not supported by any sponsor or funder.

Data Availability Statement

No new data were generated in this work. Patient privacy considerations preclude public sharing of the data supporting this case report. Further inquiries can be directed to the corresponding author.