Continuing Education Activity

This article reviews one of the paroxysmal symptom/pain syndromes, Lhermitte's sign, a transient electric shock sensation down the spine and extremities caused by neck flexion. It is most notably caused by multiple sclerosis (MS) but is caused by numerous other lesions of the posterior columns of the cervical spinal cord. Lhermitte's sign is also classified as one of the paroxysmal pain syndromes of multiple sclerosis, a chronic, predominantly immune-mediated disease of the central nervous system. It is one of the most common causes of neurological disability in young adults globally and can cause many other neurological clinical symptoms, including mononuclear painful visual loss, spinal cord hemiparesis, mono/paraparesis, hypoesthesia, dysesthesia, paraesthesia, urinary and/or sphincter dysfunction, diplopia, oscillopsia, vertigo, gait ataxia, dysmetria, intentional/postural tremor, facial paresis, faciobrachial–crural hemiparesis, and faciobrachial–crural hemihypesthesia. This activity reviews the definition, etiology, pathophysiology, clinical and physical exam, considerations, and treatments of Lhermitte's sign.

Objectives:

• Describe the various reported causes of Lhermitte's sign.
• Identify key clinical and physical exam findings of Lhermitte's sign and how to elicit it at the bedside.
• Summarize the experimental treatment modalities for patients with Lhermitte's sign.
• Explain strategies to improve care coordination among interprofessional team members to improve outcomes for patients affected by Lhermitte's sign.

Introduction

Lhermitte's sign (also known as Lhermitte's phenomenon or the barber chair phenomenon) is the term used that describes a transient sensation of an electric shock that extends down the spine and extremities upon flexion and/or movement of the neck. It was first described by Marie and Chatelin in 1917, but was erroneously first credited to Babinski and Dubois, and thenafter credited to Jean Jaque Lhermitte through the seminal paper Les douleurs à type de décharge électrique consécutives à la flexion céphalique dans la sclérose en plaques: Un cas de forme sensitive de la sclérose multiple (1924) by Lhermitte et al. and Gutre. Lhermitte described this phenomenon in patients with multiple sclerosis and other spinal cord diseases. It was then further hypothesized that it resulted from irritation and inflammation of the spinal cord, likely in the posterior and lateral columns.[1]

Lhermitte's sign is also classified as one of the paroxysmal pain syndromes of multiple sclerosis, a chronic, predominantly immune-mediated disease of the central nervous system. It is among the most common causes of neurological disability in young adults globally. It can cause many other neurological clinical symptoms, including mononuclear painful visual loss, spinal cord hemiparesis, mono/paraparesis, hypoesthesia, dysesthesia, paraesthesia, urinary and/or sphincter dysfunction, diplopia, oscillopsia, vertigo, gait ataxia, dysmetria, intentional/postural tremor, facial paresis, faciobrachial–crural hemiparesis, and faciobrachial–crural hemihypesthesia.[2] Lhermitte's sign should not be confused with the Uhthoff phenomenon, another finding in multiple sclerosis patients that is defined by heat sensitivity after prolonged heat exposure, saunas, and hot tubs.[3][4][5] 

Etiology

Lhermitte's sign (LS) is not a disease but more of a sign or symptom. The sign is suggestive of a lesion or compression of the lower brainstem or the upper cervical spinal cord. It is a paroxysmal sensation or neuropathic pain that can develop as a result of direct or indirect demyelinating lesions in the brain and/or spinal cord and is triggered by the flexion or movement of the neck. More specifically, the neck motion activates ascending spinothalamic tracts at the cervical level that has been sensitized by the underlying process that caused the cervical spine lesion.[5] This view is supported by an MRI study of plaque formations in the cervical spine, which was found in 95% of those reporting a history of LS compared with 52% of those who did not report the sign.[6]

Other etiologies that have been shown to cause this sign, in addition to multiple sclerosis, include conditions like Bechet's disease, transverse myelitis, systemic lupus erythematosus (SLE), herpes zoster, Arnold-Chiari malformation, tumor progression causing spinal cord compression, radiculopathy, cervical spondylitis, transverse myelitis, syringomyelia, vitamin b12 deficiency, nitric oxide toxicity, subacute combined degeneration of the cord, radiation myelopathy, and chemoradiation. It is preferentially present in patients with cervical demyelinating lesions and abnormal nerve conduction studies. It is not a sensitive or specific sign for any of the disorders mentioned. Neck flexion irritates demyelinated tracts in the posterior column, causing the electric sensation experienced by patients.[7][8][9]

Epidemiology

Epidemiological studies of the incidence and prevalence of Lhermitte's sign are scant and give varying data, and there are no available statistics regarding the incidence or prevalence of Lhermitte's sign in today's global population.[10][11] However, the overall prevalence of Lhermitte's sign in patients with MS ranges from 9 to 41%.[12][6] One prospective study from 2015 of almost 700 patients with MS showed an incidence of about 16%, while another older study from 1982 reported that Lhermitte's sign was experienced by 33.3% of patients, with around 16% reporting having it occurring during their first episode of MS.[13][14][5] 

Despite the low sensitivity in those with MS, it has been said to have a very high specificity of 97% for compressive myelopathy as the underlying etiology.[15] One study also compared the prevalence in patients with MS and neuromyelitis optica (NMO). They found that the prevalence of Lhermitte's sign among MS patients (4.3%) was significantly lower than in NMO patients (20.5%) (P < 0.0001).[16] Lhermitte's sign was also found to be more common in patients with a family history of Lhermitte's sign in patients with NMO than in MS, at 12.5% vs. 5.9%, respectively. Although this symptom is typically self-limiting with spontaneous resolution after some weeks, occasionally, patients complain of increasing frequency and pain intensity.[17] The incidence and prevalence of Lhermitte's sign in rarer etiologies like vitamin B12 deficiency, Behcet disease, and SSRI discontinuation syndrome, among others, have not been well studied. 

Pathophysiology

The pathophysiology of Lhermitte's sign that is associated with the radiographical demyelinating lesions and electrodiagnostic abnormalities on nerve conduction is thought to be related to the demyelination of the dorsal columns of the cervical spine. Other reasons include compressive myelopathy with reported lesions in the dorsal columns of the caudal medulla. It is also thought to transiently activate neuropathic pain pathways, with a more recent theory being that it implicates glutamatergic signaling and microglial cell activation in the CNS.

Lhermitte's sign is thought to result from ectopic firing and hyperexcitability of demyelinated sensory neurons (in cervical regions of the spinal cord), also affecting ascending spinothalamic nociceptive signal transduction and impaired function of inhibitory GABAergic interneurons. Other proposed molecular mechanisms include downstream activated microglia that enhance pro-inflammatory cytokine signaling, activation of proteins like bradykinin with B1 and B2 receptors, upregulation of Wnt signaling, CREB phosphorylation, and other transcription factors in the CNS that augment hyperexcitability and pain.[9][18]

History and Physical

Neck movements, fatigue, stress, heat, and even yawning have been shown to trigger Lhermitte's sign.[5] Patients often describe Lhermitte's sign as an electric shock of pain that runs from the head down to the back and through the arms and legs. It happens when they bend their head down (flex their neck) and touch their chin to their chest.[7] In addition to neck flexion, it has also been described with neck extension (reverse Lhermitte's sign).[19]

Evaluation

There is no routine laboratory, radiological, or ancillary test to assess or manage Lhermitte's sign. Some prospective studies link the sign with radiographic and electrodiagnostic findings. One study showed a correlation between the clinical signs, the presence of a demyelinating lesion on cervical MRI, and the conduction delay of median and tibial somatosensory evoked potentials (SSEP). The results were clinically and statistically significant. However, the consensus is that the history and physical exam findings are sufficient.[13][7]

Treatment / Management

There is an absence of level I evidence-based treatment for those suffering from Lhermitte's sign, given the vast number of etiologies causing the condition. LS rarely elicits severe pain and discomfort as it is usually a benign finding and self-resolves. Treatment of the underlying condition, like in MS, and surgically addressing any of the compressive anatomical causes are recommended. Few reports and anecdotal evidence show that carbamazepine, oxcarbazepine, and gabapentin may benefit some patients.[20][21] Inhibition of pro-inflammatory cytokine signaling, augmentation of inhibitory cytokine signaling, and blockade of chemokine receptor-mediated inflammatory cell recruitment to the CNS has the potential for future therapies for more severe manifestations of MS-associated neuropathic pain.[9]

Interestingly, a case series demonstrated that the use of extracranial picotesla range pulsed electromagnetic fields (EMFs) effectively treated patients with Lhermitte's sign. One theory is that the reduction of axonal excitability occurs through the modulation of ionic membrane permeability. The second theory involves modulating pain control systems through neurotransmitter activity and pineal melatonin functions, as discussed earlier.[22][23]

Differential Diagnosis

The differential diagnosis of Lhermitte sign, besides MS, has been reported in the literature and includes tumor progression causing spinal cord compression, radiculopathy, cervical spondylitis, transverse myelitis, subacute combined degeneration of the cord, radiation myelopathy, parasitic invasion of the cord, Arnold-Chiari malformation, high dose chemoradiation (cisplatin), trauma, arachnoiditis, Herpes zoster toxicity, syringomyelia,  Behcet disease, vitamin B12 deficiency, nitric oxide toxicity, systemic lupus erythematous, and post-dural puncture headache.[24][25][26][19]

Radiation Oncology

Lhermitte's sign has been noted as a potential side effect of radiation oncology therapies, specifically as an early delayed radiation injury. These often occur within four months of radiation therapy.[27][25]

Medical Oncology

Cisplatin or docetaxel neurotoxicity has been tied to Lhermitte's sign.[25]

Prognosis

Lhermitte's sign or syndrome is not a disease process, and it is usually intermittent upon neck flexion. The prognosis of the disease process underlying the Lhermitte's sign is variable.

Complications

There are no known complications related to Lhermitte's sign. However, it is occasionally reported as a facet of a discontinuation syndrome related to certain medications. Psychotropic medications such as SSRIs and SNRIs, specifically paroxetine and venlafaxine, have been shown to have a reported association. Fluoxetine, given the extended length of its half-life, has less likelihood of causing Lhermitte's sign upon sudden discontinuation.[24] On the other hand, paroxetine has a shorter half-life and is more likely to cause discontinuation syndrome. In dentistry, there have been studies that found Lhermitte's sign associated with nitrous oxide abuse (caused by depletion of vitamin B12).[26][19]

Consultations

In the case of multiple sclerosis, an experienced neurologist should be consulted if demyelinating disorders are suspected.

Deterrence and Patient Education

No active intervention is required by healthcare providers beyond education and reassurance; the syndrome usually resolves spontaneously over a period of months to a year. In rare cases, it can be treated with neuropathic pain medication if refractory and recurrent.[28]

Pearls and Other Issues

• Lhermitte's sign generally occurs with pathologies involving the cervical spinal cord but is not specific to etiology.
• It often occurs in patients with multiple sclerosis, cervical spondylotic myelopathy, chemotherapy, radiation myelopathy, and B12 deficiency, among others.
• Increased spinal cord metabolic activity and positive positron emission tomography (PET) imaging have been described in association with Lhermitte's sign.
• The overall incidence and prevalence of Lhermitte symptoms are difficult to estimate but more studied in MS patients. 
• Patients can experience Lhermitte's sign intermittently as it does not have to always happen with the same degree of neck flexion. It may be infrequent or occur with slight to dramatic flexion of the head or neck as well as with extension of the neck.
• Delayed onset Lhermitte's sign has been reported following head and/or neck trauma. This occurs several months following injury, without associated neurological symptoms or pain, and typically resolves within 12 months.
• As a misnomer, Lhermitte's "sign" is not truly a sign, at least in the traditional medical terminology. Rather, it is a symptom.[29][30][28]

Enhancing Healthcare Team Outcomes

Lhermitte's sign is a symptom often secondary to an underlying chronic disease like (but not limited to) MS, which can sometimes follow an unpredictable trajectory. It is best to enhance patient outcomes by integrating an interprofessional team-based approach, including nurses, mid-level practitioners, physical therapists, and physicians should be used in managing patients with with multiple sclerosis or other conditions that can produce this sign. All practitioners with diagnostic and assessment duties should be familiar with how to perform the sign and its clinical significance. They should also be able to explain the test and its significance in laypeople's terms to the patient. Consider speaking to the patient about implementing new clinicians and services to their overall care, such as palliative medicine, as such resources can offer a new range of support to the family and the patient. [Level 5]