Chronic Inflammatory Demyelinating Polyradiculoneuropathy During the COVID-19 Pandemic: Telemedicine Limitations and Strategies for Improvement

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a relapsing-remitting or progressive inflammatory neuropathy, which can present in a multitude of phenotypes. It can be a challenging condition to diagnose and requires thorough clinical evaluation and electrodiagnostic testing. With the outbreak of coronavirus disease in 2019 (COVID-19), large portions of the medical field converted to telemedicine to facilitate patient visits. We report a case of a 50-year-old female who was seen via video visit during the COVID-19 pandemic who was later diagnosed with CIDP and treated with intravenous immunoglobulins with improvement in clinical examination and electrodiagnostic testing. This case highlights the limitations of performing the neuromuscular examination via telemedicine.


Introduction
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is a relapsing-remitting or progressive inflammatory demyelinating polyneuropathy, which has a varied clinical presentation [1]. It has an estimated prevalence of 0.8 to 9 cases per 100,000 and is more common in men [2][3][4]. CIDP can be a challenging diagnosis for physicians due to the heterogeneity of presentations, ranging from distal vs proximal onset, symmetric vs asymmetric onset, and sensory vs motor variants. In 2010, the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) revised their 2006 criteria which they validated in multicenter European cohorts and have become the standards for clinical care [5]. The EFNS/PNS criteria define typical CIDP as "having proximal and distal weakness and sensory dysfunction of all extremities;" this is compared to atypical CIDP in which there can be predominantly distal asymmetric or focal symptoms, including pure motor or sensory [1,5]. Other supportive criteria include elevation of protein in cerebrospinal fluid (CSF), response to treatment, and exclusion of other conditions [1,5]. These criteria rely on clinical features and electrophysical evidence (conduction block, temporal dispersion) of demyelination to diagnose CIDP. Yet, even with these standards, misdiagnosis of CIDP is often seen.
The coronavirus disease 2019 (COVID-19) pandemic resulted in paradigm shifts in medical practice and clinical care. During the early stages of the pandemic, most non-acute care transitioned to virtual visits using technology such as video or telephone to conduct visits. This resulted in limited physical examination information which could be acquired by the provider.
This report discusses the case of a woman who presented via a virtual visit for symptoms of tingling in her extremities and was later diagnosed and treated for CIDP with clinical improvement.

Case Presentation
A 50-year-old female with a past medical history of anxiety was referred to the neurology clinic due to symptoms of paresthesias in her hands and feet. She reported that she had paresthesias in her fingers for the year prior to presentation which gradually progressed to symptoms in her feet over the course of the last few months. She described a sensation of burning in her feet as well. Prior to coming to the neurologist, she had tried acetaminophen, non-steroidal anti-inflammatory agents, gabapentin and duloxetine, which did not provide significant improvement. She had been supplementing with zinc, iron, calcium, biotin, and other vitamins.
Due to the COVID-19 pandemic, the patient participated virtually in the visit via secure tele-video services. Examination was limited due to the visit modality but included a normal mental status examination with intact orientation, concentration, and attention. The patient had fluent speech with no difficulties naming objects or repeating commands. Cranial nerve examination demonstrated intact extraocular muscle function, intact facial symmetry, and no dysarthria. Motor examination did not show any apparent muscle atrophy or obvious weakness or asymmetry, and the patient had a normal gait with normal based stance. Functional testing was attempted by having the patient go up and down a set of stairs. While she was able to perform this task, the visual observation was limited by the placement of the camera. Reflexes and sensation could not be assessed.
On the day of the visit, the patient had a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) done due to an exposure which resulted positive, though the patient was asymptomatic. She was not started on any treatment for COVID-19. Other laboratory testing done prior to the visit included a normal C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), vitamin B1, hemoglobin A1c, low-density lipoprotein, and thyroid-stimulating hormone. Vitamin B6 was elevated at 83 ng/mL (normal: 2.1-21.7 ng/mL). Based on the history and limited examination, it was felt that the patient had a sensory neuropathy of unclear etiology with the possibility of a superimposed median entrapment neuropathy (carpal tunnel syndrome). Due to her COVID diagnosis as well as patient preference, the plan was made to follow-up for a face-to-face visit in four weeks with an electromyography/nerve conduction study (EMG/NCS). Additionally, further laboratory workup including Lyme disease, antineutrophil cytoplasmic antibodies (ANCA), zinc, copper, hepatitis panel, and serum protein electrophoresis with immunofixation were ordered, all of which resulted normal.
The patient presented for EMG/NCS and was noted on physical examination to display evidence of weakness of the bilateral deltoids (4/5), wrist flexion/extension (4/5), finger flexion/extension (4-/5), and foot dorsiflexion (right 4/5, left 5-/5). Additionally, there were absent reflexes except for 1+ at bilateral patella and sensory examination was notable for decrease of pinprick and vibration sensation in the feet. The EMG/NCS showed evidence of a severe demyelinating sensorimotor polyneuropathy with axon loss, with temporal dispersion noted (Table 1, Figure 1). The needle examination showed evidence of abnormal spontaneous activity in the right first dorsal interosseous, flexor carpi radialis, and abductor pollicis brevis muscles with chronic reinnervation changes in the right extensor digitorum, first dorsal interosseous, abductor pollicis brevis, and tibialis anterior muscles. Based on this, additional workup was performed, including laboratory testing and cerebrospinal fluid analysis ( Table 2). She was treated with intravenous immune globulins (IVIG) 400 mg/kg/day for five days followed by maintenance with 1g/kg divided over three days every three weeks. She also underwent physical and occupational therapy.   At the follow-up visit two months later, she had improved significantly and was able to perform all of her activities of daily living following IVIG therapy. She had no adverse reactions to the therapy. Neurologic examination was notable for full strength in both upper and lower extremities as well as 2+ reflexes throughout. The plan was to continue IVIG and repeat an EMG/NCS to assess for any electrodiagnostic changes. Follow-up EMG/NCS showed evidence of a diffuse demyelinating sensorimotor polyneuropathy, though when compared to the prior study there was a significant improvement in the degree of demyelination and axon loss ( Figure 2).

FIGURE 2: Follow-up EMG/NCS
The left median CMAP distal latency was prolonged and the conduction velocity was slowed. The left ulnar, left tibial and right fibular CMAPs distal latencies were prolonged. The left ulnar, median and radial SNAP distal latencies were prolonged, amplitudes were decreased and the conduction velocities were slowed. The left sural SNAP was normal. This electrodiagnostic study showed evidence of a diffuse demyelinating sensorimotor polyneuropathy.
CMAP: compound motor action potential; SNAP: sensory nerve action potential

Discussion
This case presentation highlights the difficulty in diagnosing CIDP as well as the importance of close clinical follow-up and physical examination. CIDP can be a difficult diagnosis and prompt treatment can result in favorable outcomes and limited morbidity, as shown in this patient. With virtual visits becoming a standard part of clinical care for the foreseeable future, it is important to systematically and comprehensively evaluate patient symptoms. In this case, the patient presented with symptoms of neuropathy in the distal extreme ities which had progressed in the months prior to presentation. A detailed history coupled with the limited virtual examination allowed for the correct workup to be ordered including laboratory testing and electrodiagnostic studies. The video modality prevented the detection of subtle signs of distal sensorimotor polyneuropathy like vibratory sensation loss, mild proprioceptive deficits, absence of reflexes, distal muscle weakness without atrophy (sign of conduction block). The time period between the virtual visit and in person examination was limited, allowing for expedited assessment of the patient's physical symptoms by a neuromuscular physician. However, establishing the precise diagnosis was difficult in the absence of a faceto-face physical examination. This made the case appear less urgent, which could have resulted in a poor outcome.
Electrodiagnostic findings of CIDP can include slowing of conduction velocities, prolongation of distal motor latencies, temporal dispersion, conduction block, and prolongation of F-waves [5]. Temporal dispersion is a reduction in proximal compound motor action potential (CMAP) amplitude compared with distal CMAP amplitude when the proximal CMAP duration increases by > 20% This patient's initial EMG/NCS shows classic findings of demyelination with prominent evidence of temporal dispersion in all motor nerves.
The electrodiagnostic findings coupled with the physical examination were consistent with a diagnosis of