Lhermitte Sign
- Article Author:
- Dac Teoli
- Article Author:
- Franklyn Rocha Cabrero
- Article Editor:
- Sassan Ghassemzadeh
- Updated:
- 10/23/2020 4:23:35 PM
- For CME on this topic:
- Lhermitte Sign CME
- PubMed Link:
- Lhermitte Sign
Introduction
Lhermitte’s sign (also known as Lhermitte’s phenomenon and the barber chair phenomenon) describes a transient sensation of an electric shock extending down the spine and/or extremities upon flexion of the neck, often a sequela of neurologic disease. It was first described by Marie and Chatelin in 1917. It was erroneously credited to Babinski and Dubois, and correctly 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 it in multiple sclerosis and spinal cord diseases and further hypothesized it was a result of irritation and inflammation of the cord, likely in the posterior and lateral columns.[1]
Lhermitte's sign is classified as one of the paroxysmal pain syndromes of multiple sclerosis. Multiple sclerosis is 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. The new Mc Donald's criteria 2017 establishes clinical and radiographical dissemination of time and space of symptoms, presence of at least one lesion in at least two out of four CNS areas: Periventricular, cortical or juxtacortical, infratentorial and spinal cord. Additional radiographical and laboratory criteria include new T2 and/or gadolinium (Gd)-enhancing lesion on follow-up MRI (with reference to a baseline scan), irrespective of the timing of the baseline MRI, the simultaneous presence of asymptomatic Gd-enhancing and nonenhancing lesions at any time, and presence of oligoclonal bands in CSF. Common initial clinical symptoms include mononuclear painful visual loss, spinal cord hemiparesis, mono/paraparesis, hypoesthesia, dysesthesia, paraesthesia, urinary and/or sphincter dysfunction, diplopia, oscillopsy, vertigo, gait ataxia, dysmetria, intentional/postural tremor, facial paresis, faciobrachial–crural hemiparesis, and faciobrachial–crural hemihypoesthesia. It affects multiple organ systems of the patient. [2]
Lhermitte's sign or symptom should not be confused with Uhthoff phenomenon, another finding in multiple sclerosis patients. The phenomenon is defined by heat sensitivity after prolonged heat exposure, saunas, and hot tubs. Although frightening to some patients, these events are not a true advancement of disease (such as in multiple sclerosis). [3][4][5]
Etiology
Lhermitte's sign is not a disease, it is a paroxysmal multiple sclerosis-induced neuropathic pain syndrome. It develops as a result of direct or indirect demyelinating lesions in the brain and/or spinal cord. Specifically, it activates ascending spinothalamic tracts at the cervical level that have been sensitized by demyelination. This view is supported by an MRI study of plaque formations in the cervical spine, which were present in 95% of those with a history of Lhermitte’s sign compared with 52% of those who did not report the sign. [6]
Other etiologies besides MS, includes tumor progression causing spinal cord compression, radiculopathy, cervical spondylitis, transverse myelitis, subacute combined degeneration of the cord, radiation myelopathy, chemoradiation, among others. 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 (LS) are scant. One prospective study showed that the incidence of LS was about 16% in almost 700 patients. [10] An old study reported that that LS was experienced by 33.3% out of 114 patients of MS; and in 16%, it was reported to have occurred in the first episode of MS.[11] [5] One study compared the prevalence in patient with MS and Neuromyelitis Optica (NMO). They found that the prevalence of LS among MS patients (4.3%) was significantly lower than NMO patients (20.5%) (P < 0.0001). 5.9% of the MS and 12.5% of the NMO patients had a positive family history of Lhermitte’s sign. It was observed that a higher proportion of patients with NMO rather than MS experienced the sign (20.5% vs. 4.3%). [12]. The overall prevalence of LS ranges from 9-41 % [13][6]. Although this symptom is typically self-limiting with spontaneous resolution after some weeks, occasionally, patients complain of increasing frequency and pain intensity. [14] The incidence and prevalence in rarer etiologies, including Vitamin B12, Behcet's disease, SSRI discontinuation syndrome, among others have not been studied in the population. There are no available statistics regarding the incidence or prevalence of Lhermitte's sign in today's global population. [15][16]
Pathophysiology
Lhermitte's sign pathophysiology is related to demyelination of dorsal columns of the cervical spine, associated with radiographical demyelinating lesion and electrodiagnostic abnormalities on nerve conduction. It is also associated with compressive myelopathy with reported lesions in the dorsal columns of the caudal medulla. As mentioned before, it is thought to transiently activate neuropathic pain pathways. A more recent theory is that it implicates glutamatergic signaling and microglial cell activation in the CNS. In the case of Lhermitte's sign, it is thought to result from ectopic firing and hyperexcitability of demyelinated sensory neurons (in cervical regions of the spinal cord). It involves 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] [17]
History and Physical
Neck movements, fatigue, stress, and heat can trigger Lhermitte’s sign. 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 and touch their chin to their chest. [7]
Evaluation
There is no routine laboratory, radiological, or ancillary test to assess or manage Lhermitte's sign. Some prospective studies linking 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 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. [10][7]
Treatment / Management
There is an absence of level I evidence-based treatment for LS. Usually, it is benign and self-resolves. Rarely, patients elicit severe pain and discomfort. Few reports and anecdotal evidence show that carbamazepine[18], oxcarbazepine, gabapentin, may be beneficial in some patients. [19] Inhibition of pro-inflammatory cytokine signaling, augmentation of inhibitory cytokine signaling and blockade of chemokine receptor-mediated inflammatory cell recruitment to the CNS, have potential for future therapies for more severe manifestations of MS-associated neuropathic pain. [9]
Interestingly, 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. [20][21]
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's disease, vitamin B12 deficiency, nitric oxide toxicity, systemic lupus erythematous, and postdural puncture headache.[22][23][24]
Radiation Oncology
Medical Oncology
Cisplatin or docetaxel neurotoxicity has been tied to Lhermitte's sign.[23]
Prognosis
Lhermitte's sign or syndrome is not a disease process itself, and it is usually intermittent in nature 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. [22] On the other hand, paroxetine, has a shorter half-life and more likely to cause discontinuation syndrome. In dentistry, there have been studies that found Lhermitte's sign associated with nitrous oxide abusers (caused by depletion of vitamin B12). [24]
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.[26]
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 incidence and prevalence of Lhermitte symptom are difficult to estimate.
- A patient can experience Lhermitte's sign intermittently. 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.
- 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 resolving within 12 months.
- As a misnomer, Lhermitte's "sign" is not truly a sign at all, at least in the traditional sense of medical terminology. Rather, it is a symptom.[27][28][26]
Enhancing Healthcare Team Outcomes
Multiple sclerosis is a chronic disease that can sometimes follow an unpredictable trajectory. It is best to enhance patient outcomes by integrating a team-based approach, including nurses, physician assistants, and physicians should be used in managing patients who live with multiple sclerosis. Consider speaking to the patient about implementing new physicians and services to their overall care, such a palliative medicine, as such resources can offer a new range of support to the family and the patient. [Level V]