Extracranial Herpetic Paresis

Segmental zoster paresis (SZP) is a rare complication of varicella zoster infection that occurs due to the spread of the infection from the posterior horn of spinal cord to the anterior horn and the motor nerve root. As recognizing segmental zoster paresis is important in the differential diagnosis of muscle weakness of other origin, information about demographic (gender and age), clinical presentation, diagnosis, treatment, and course about published patients with SZP was extracted from PubMed database. SZP is classified into several categories: paresis of upper extremity, lower limb involvement, diaphragmatic involvement, and abdomen involvement. Published experiences have shown that clinical course and electromyoneurography of paretic muscle are the most important in the diagnosis; physical therapy is the most common therapy in these patients and their prognosis is generally good except diaphragmatic paresis, where there is no significant recovery in most number of patients.


Introduction
Herpes zoster (HZ) is an infection of dorsal root ganglion characterized by a painful cutaneous rash.It is believed that reactivated varicella zoster virus (VZV) migrate from dorsal root ganglion in retrograde direction along the sensory nerve to the skin, where it makes the characteristic dermatomal rash [1].
The initial infection caused by varicella or chickenpox occurs during childhood.After that, the virus then exists as a latent infection of sensory ganglia from which it may reactivate many years later and cause herpes zoster.
The virus can be recovered from skin lesion and can cause an inflammatory reaction in sensory ganglion, dorsal root, and posterior horn of spinal cord [2].
Postherpetic neuralgia is the most common complication associated with extracranial HZ.Pain persisting 90 days or longer after the onset of the shingles rash is called postherpetic neuralgia [3,4].Postherpetic neuralgia usually remits spontaneously, but some patients could have pain for all their life.
Beside postherpetic neuralgia, segmental herpetic paresis is another complication of HZ, and they often occur together.
Flaccid muscle paralysis rarely occurs due to the spread of the infection from the posterior horn of spinal cord to the anterior horn and the motor nerve root (Figure 1) when weakness generally corresponding to the dermatomes in which cutaneous lesions develop [5].
This finding supports the enhancement of spinal nerve roots on MRI that was clinically symptomatic [6], attributed to autoimmune inflammation or 1 Please use Adobe Acrobat Reader to read this book chapter for free.
Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.vasculitis [7]; brachial plexus inflammation; and myelin destruction with intact axons found postmortem [8].
The association of muscle paralysis and herpes zoster was first reported by Broadbent in 1866.When he described the case to zoster described as "frozen shoulder" [9], it is noted rarely between 0.5% [10] and 0.8% of segmental motor paralysis between all patients with HZ [11].
In patients with dissociation between motor and dermatomal involvement, a possible explanation could be viral spread to anterior roots without corresponding axonal transport through the sensory nerves [6,12].Some patients may have zoster infection without vesicular eruptions, which is called "zoster sine herpete."This diagnose is safer by a rise VZV antibodies.These patients may have the same neurologic manifestations, including muscular paralysis [13].
As there are no certain standards regarding diagnosis and treatment of segment zoster paresis, we have listed in this paper experiences from literature related to the topic.
The aim of this study was to summarize the experiences related to its clinical manifestation, applied diagnostics, treatment, and patient outcome.

Methods
We searched the PubMed database for literature on herpes zoster infection and extracranial motor paresis in adults (last search on September 2019).The search was limited to full-length articles written in English and a study population that included adults aged 18 years and older.A combination of the following search terms was used "herpes zoster, paresis, complications."As a result, 74 articles were retrieved.
The reference list was also searched for relevant manuscripts not retrieved from PubMed.
Studies included in the final review met the following criteria: (1) infection with herpes zoster virus, (2) motor paresis, and (3) adult study population.
They encompass original articles, technical reports, clinical observations, and single case reports.

Data extraction and synthesis
For comparison across the reports, the sample size was extracted along with demographic information (gender and age), clinical presentation, laboratory

Lower limb involvement
There are 43 presented patients with isolated segmental zoster paresis of one leg in the total of 26 previously published papers.Nine of these papers present only zoster paresis of the lower limbs, while the rest of them describe affection of arms and torso, also.According to available information, mean age of this group of patients was 64.19 AE 15.28, and the patient group was dominated by males (20/12).
Almost all patients had weakness in one leg; but 3 them developed weakness in both legs.
In most cases, proximal muscles were affected (in 13 patients); then in much lesser number, distal muscles (6 patients) were affected; and only 4 of them had developed entire limb weakness.
Muscle atrophy was seen in 3 patients in this group (in M. quadriceps).
Denervation has been the most common report (in 18 patients) among patients with electromyoneurography performed; reduced interference pattern was found in 12 patients and polyphasia was present in 4 patients.
Laboratory is sporadically performed in these patients: ELISA for HZV in sera done in 2 patients and were positive in IgG and IgM fraction in both of them, and in the third patient, performed VZV complement fixation was positive, also.
A lumbar puncture was done in a small number of patients [44,45]: cerebrospinal fluid (CSF) was normal in two cases, but in the other three patients, hyperproteinorachia was discovered.
The patient with flaccid paraparesis had elevated lymphocytes and hyperproteinorachia in cerebrospinal fluid, while PCR for VZV was positive in this case.
MRI of lumbar spine performed in 4 patients did not explain the nature of deficit in these patients, and 2 patients were generally described by degenerative changes, 1 was normal, and in 1 enlargement and T2 signal in the left femoral nerve was found.
There is no information about outcome of the disease for some patients.However, among patients who were followed for a period of time, a majority of them (20 patients) fully or almost fully recovered in the period between 2 and 9 months; 11 patients recovered incompletely; 2 patients did not recover, and 2 patients had with lethal outcome.
Although EMNG of phrenic nerve is one of the reliable signs of affection in this nerve, it is rarely performed (1 patient).More often, fluoroscopy is performed when weakness of the diaphragm is suspected (7 patients).Although not a reliable sign of weakness of the diaphragm, X-ray often done in the case of a suspected weakness of the diaphragm paresis (13 patients).
Phrenic nerve affection is usually followed by dyspnea, but there is a case with hemidiaphragmatic paresis on X-ray, but without visible dyspnea.
To the contrary, there are cases with normal hemidiaphragm position on non-CT chest, when dyspnea is present clinically.
Half of the patients [47] did not recover after significant a follow-up period (1 year and more).Partial recovery was seen in significantly smaller number of patients [48], while complete recovery was present in the fewest number of patients [42].
In most cases, the type of treatment of these patients was not mentioned: Acyclovir in 2 patients, Valacyclovir in 1 patient, physical therapy in 1 patient, and topical hydrocortisone in 1 patient.
The incidence of segmental zoster abdominal paresis mimicking an abdominal hernia is relatively rare.After review from 2013 [49] with 36 patients and segmental zoster paresis of abdominal muscle ( 14), 8 papers with 11 patients with this problem have been published.
Their mean age (66.5 years) is not much different from the average age of the patients in the review paper from 2013 (67.5 years).
As in the review paper, the predominant level of abdominal involvement of herpes zoster was Th11.
It is the most important to exclude organic disease of the abdomen in the case of abdominal herniation when beneficial are ultrasound or CT abdomen showing normal results.This is particularly relevant when the abdominal herniation is complicated with, for example, ileus, which is described in 1 patient.
The presence of denervation potentials in EMG of paraspinal (3 patients), or abdominal muscles (2 patients), indicates the involvement of the abdominal musculature, which separates EMG as well as a particularly useful diagnostic method in this case.
Prognosis of these patients is generally good, and there is full recovery in almost all of them in just few months [42,43,50].
Acyclovir is rarely used as a therapy in these patients (2 patients).

Discussion
Increasing rate of herpes zoster infection with increasing age particularly after age 50 years can be explained by natural decline in cell-mediated immunity to VZV with age [51]: the mean age of patients with the most frequent segmental paresis was for arms 68.56 AE 11.97 years and for legs 64.19 AE 15.28 years.
Healthy people can get HZ [31], although immunocompromised individuals are known to be at increased risk of reactivation and VZV infection [52].
The most immunocompromised patients with zoster paresis have a coexisting malignancy, diabetes mellitus, and chronic steroid therapy [53]: 7 patients suffering from lymphoma and 2 with carcinoma mammae in group with arm segmental paresis and 1 patient with segmental paresis of leg had lymphatic leukemia; as per 4 patient in each group and 1 in group with diaphragmatic paresis suffered from DM and as per 4 patient in both groups of patients with limb segmental paresis on chronic steroid therapy because of autoimmune disorders.
In clinical presentation of HZ infection, pain usually precedes the onset of the rash, and most patients have skin lesions that develop within 7 days of onset of pain [32].
Motor palsy is usually segmental, with abrupt onset reaching its maximum within a few hours [31], corresponding to the dermatomes with cutaneous lesions [18].Interval between skin eruptions and onset of muscle weakness is generally about 2 weeks in cases with developing segmental paresis [54], but there are some reports of weakness and rash developing simultaneously [55].With reference to the literature, maximal rash-to-weakness interval in patients with segmental limb paresis was 19 days [37] although there are different experiences.Variations in rashto-weakness interval is best illustrated in a study of 51 patients: <3 days in 6 patients, 3-6 days in 12, 7-10 days in 14, 11-14 days in 11, 15-20 days in 5, 21-28 days in 2, and 29-35 days in 1 [33].A delay of 4.5 months has been documented in a patient with diaphragmatic paralysis [56], when the average minimum duration of weakness was 193 days [57].The fact that the phrenicus nerve is a motor nerve and is the longest in the body is the explanation for such a long period of time required for the development of paralysis of phrenic nerve.
Limb involvement by segmental zoster paresis is seen from 0.5 to 0.8% of all patients with cutaneous zoster [10,11].
Upper extremity involvement is the most common region of extracranial zoster paresis involvement.There are a total of 101 patients with segmental paresis of upper limbs in recently published papers: 55 women and 45 men (Tables 1 and 3).
Segmental zoster paresis of the legs present in less than half the number (43 patients with leg involvement) dominated by males (20/12) (Tables 2 and 3).
Besides weakness in upper limbs affected by segmental zoster paresis, in 9 patients, muscle atrophy was detected and in 3 patients in group had leg affection (in M. quadriceps).
It is important to recognize severe muscle weakness and atrophy in herpes zoster paresis of limb because it can be so severe to cause marked dislocation of the joint.Because of that, except pain medication, treatment for segmental paresis includes exercise that may prevent muscle atrophy and contractures [17].
Risk of postherpetic neuralgia and pain after 3 months of HZ infection increased and occurs in 8-70% of patients with HZ.People above 50 years are 15 times more likely to develop this complication [79].
In studies involving a larger number of patients with segmental zoster paresis, postherpetic neuralgia persisted in 2 and 6.6% [32,33].
Among the patients monitored over several months and multiyear period, 13 patients with segmental zoster paresis of arm and 6 patients with paresis of leg have reported pain as the postherpetic neuralgia type (Tables 1-3).
The clinical diagnosis makes pain followed by rash and by weakness at the end.Once the rash appears, diagnosis of HZ can be made and laboratory confirmation is not always required.Some patients may have zoster sine herpete, and it is zoster infection without vesicular eruptions.In making this diagnosis benefit is from varicella zoster virus antibodies in sera or cerebrospinal fluid [13].In rare cases with herpes sine herpete, cases with prolonged period between rash and muscular weakness and cases with  dissociation between motor segment and level of dermatomal involvement recommended laboratory confirmation of VZV infection because herpes zoster paresis may be difficult to recognize in these cases.
Possible explanation for zoster sine herpete and for herpes zoster paresis without associated dermatome eruption could be viral spread to anterior roots without corresponding axonal transport through the sensory nerve [6,12].
Electrophysiologic study of segmental zoster paresis found reinnervation of muscles, absence of fasciculations in involved muscles, and slow motor nerve conduction velocity suggesting motor axon injury rather than anterior horn cells [80].
In electromyoneurography of 58 patients with arm paresis, denervation potential has been described in most cases (51 patients), often associated with reduced pattern and polyphasia of motor unit potentials in most cases (17 patients) and reduced motor or sensor velocity in 4 patients.
Denervation has been the most common report (in 18 patients) among patients who had electromyoneurography of leg paresis; reduced interference pattern in 12 patients and polyphasia in 4 patients were present.
Although EMNG of phrenic nerve is one of the reliable signs of affection in this nerve, it is rarely performed (1 patient).
The presence of denervation potentials in electromyography of paraspinal (3 patients), or in abdominal muscles (2 patients), indicates involvement of the abdominal musculature, which separates EMG as well as a particularly useful diagnostic method in case of abdominal wall zoster paresis (Table 5).Because of its selflimited nature and good prognosis, recognition of this complication is important to prevent unnecessary diagnostic studies and procedures, and because of that, abdominal hernia needs no surgery.Thus, electrodiagnostic studies can be effectively used to confirm the diagnosis.
The treatment for segmental zoster paresis includes physical therapy for weakened muscles and protection contractures with graduated exercise.This program may prevent muscle atrophy.Muscle weakness and atrophy can be so severe to cause marked dislocation of the involved joint [17].
In segmental paresis of arm, in most cases, a way of treating these patients is not mentioned.In others, physical therapy was the most common way of treating these patients (24 reported patients) and patients with leg affection, also (4 patients).
Beside physical therapy, for these patients, it is often necessary to provide pain medication, and therefore they are usually given analgesics, opioids, Amitriptyline, Pregabalin, and Gabapentin.
According to some recommendations, initiating treatment with antiviral agents as soon as the rash appears is the key to improve the outcome of herpes zoster.A 3week course of oral corticosteroids (prednisone 60 mg/day for first week, 30 mg/ day for second week, and 15 mg/day for third week) administered with the antiviral medication also has some effect on severity and duration of pain and may decrease the incidence of postherpetic neuralgia [87].Local, epidural, and sympathetic blocks, if administered within the first 2 weeks of disease, have been reported to decrease pain and the incidence of postherpetic neuralgia [88,89].
Initiating treatment with antiviral agents as soon as the rash appears is the key to improve the outcome of herpes zoster.As the effect of this therapy on the development of segmental paresis is not known, despite such recommendations, it appears that very small number of patients from the literature with segmental zoster paresis was treated with antiviral medication and corticosteroids.Among the antiviral drugs, Valacyclovir and Acyclovir (in total 13 patients) and corticosteroids in total 5 patients were usually used.
Previous experience in groups with a higher number of patients with segmental zoster paresis shows that the outcome of lower motor neuron involvement is elatively good [55].Motor paralysis is recovered completely or nearly completely in 50-70% of cases usually within 12 months, spontaneously [11].The time of recovery varies from 1 to 2 years [90].Only 15% have significant deficit [33].
Among presented patients with known clinical outcomes, complete or near complete recovery is recorded in 9 patients with arm involvement and in 20 patients with leg affection.
Incomplete recovery was reported in 3 patients with arm affection and in 11 patients with leg affection (Tables 1-3).Two patients from each group, with segmental paresis of arms and legs, had no clinical recovery.As possible explanation of absence of a complete recovery after motor segmental paralysis caused by herpes zoster is glial scar polyradiculitis evident on MRI [91].
Prognosis in patients with diaphragmatic paralysis is not good because of prolonged reinnervation of diaphragm due to relatively long course of phrenic nerve affection, and the lack of spontaneous recovery is not surprising [74].It is common for zoster phrenic nerve affection and associated diaphragmatic paralysis to be permanent, but occasionally, recovery has been reported after 7 and 12 months [92].
There are interesting experiences related to Piramat.It may reverse phrenic nerve paralysis in patients with diabetes, but there are no data about its use in patients with zoster-induced diaphragmatic paralysis [90].
It is important to distinguish segmental zoster paresis of abdominal wall from real abdominal wall hernia because abdominal wall hernia is mainly treated by surgery, while segmental zoster abdominal paresis needs no surgery.Ultrasonography or computed tomography (CT) is necessary to do in this case.Electromyographic testing revealed denervation in the affected dermatome and pseudohernia caused by abdominal wall paresis and is of great benefit in defining the problem and recommended in these situations.

Conclusion
Segmental zoster paresis is a rare complication of VZV infection.Increasing rate of herpes zoster infection and its segmental paresis is confirmed by the mean age of presented patients-it is above 65 years.
Recognizing segmental zoster paresis is important in the differential diagnosis of muscle weakness of other origin-it is of particular importance to perform electromyoneurography of paretic muscle.
Physical therapy is the most common therapy for these patients, although a lot of patients did not conducted any specific way of treatment.
Prognosis for these patients is generally good, and there is full recovery in most cases, except VZV infection of phrenic nerve and diaphragmatic paresis, where there is no significant recovery of muscle weakness in significant number of patients.

Figure 1 .
Figure 1.Origin of segmental zoster paresis: the spread of varicella zoster infection from the posterior horn of spinal cord to the anterior horn and the motor nerve root.

Table 1 .
Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.List of studies that reviewed herpes zoster infection and motor paresis of only upper limbs.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.

Demographics, medical history Subjective complaints Neurological impairments EMG findings Other tests Treatment Course/outcome
Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.

Demographics, medical history Subjective complaints Neurological impairments EMG findings Other tests Treatment Course/outcome
Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.

Demographics, medical history Subjective complaints Neurological impairments EMG findings Other tests Treatment Course/outcome
Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.

Table 2 .
Lists of studies that reviewed herpes zoster infection and motor paresis of arms and legs.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.
18Human Herpesvirus Infection -Biological Features, Transmission, Symptoms, Diagnosis … Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.

21
Extracranial Herpetic Paresis DOI: http://dx.doi.org/10.5772/intechopen.90493Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.

Table 3 .
Lists of studies that reviewed herpes zoster infection and motor paresis of only lower limbs.Please useAdobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.

Table 4 .
Lists of studies that reviewed herpes zoster infection and motor paresis of diaphragmatic paralysis.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.

28
Human Herpesvirus Infection -Biological Features, Transmission, Symptoms, Diagnosis … Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here. r-

Table 5 .
Lists of studies that reviewed herpes zoster infection and motor paresis of abdominal wall.Please use Adobe Acrobat Reader to read this book chapter for free.Just open this same document with Adobe Reader.If you do not have it, you can download it here.You can freely access the chapter at the Web Viewer here.