**7. Myelitis**

VZV myelitis is a rare clinical manifestation. However, Brown-Séquard syndrome and transverse myelopathy may occur as a complication of herpes zoster infection [6, 7, 29–31]. Previous reports revealed that myelitis occurred in elderly or immunocompromised patients, such as those with HIV infection, and this condition often had severe sequelae such as motor paralysis [6, 7]. MRI shows low to equal signal intensity on T1-weighted images and high signal intensity on T2-weighted images, and sometimes, contrast enhancement can be observed as spinal cord lesions. In addition, MRI enhancement may be observed not only in the lesions in the spinal cord but also in the meninges around the spinal cord as well as in the dorsal root nerve, and these findings indicate myeloradiculitis.

Myelitis is often characterized by myelopathy at a level consistent with the spinal segment affected by herpes zoster. As a pathogenesis of this condition, reactivated VZV in the dorsal root ganglion of the spinal cord directly invades the spinal cord from the dorsal root nerve, resulting in myelitis [6, 7]. Moreover, spinal cord lesions are caused by vasculopathy, such as damage to the anterior spinal artery due to vasculitis, similar to cerebral infarction after herpes zoster infection, and this may be considered another mechanism.

#### **7.1 Case 7: myelitis**

The patient was a 60-year-old man with right lower extremity paralysis and sensory disturbance of the right trunk and lower extremity who was diagnosed with VZV myelitis based on CSF examination. MRI of the spinal cord showed a highsignal lesion in the right posterior funiculus at the thoracic vertebral level of Th6 and Th7, which should indicate that VZV directly invaded the spinal cord from the dorsal root.

#### **7.2 Case 8: myelitis**

An 87-year-old woman developed weakness of the right lower limb 2 days after developing herpes zoster lesions in the right side of the chest. Neurological examination revealed a spastic palsy in the right lower limb and loss of pain and temperature sensation in the left side to T6. However, vibration and position senses were not impaired in both sides. Thus, the patient presented with incomplete Brown-Séquard syndrome. Spinal T2-weighted MRI images showed a high-intensity lesion in the right side of the spinal cord except at the posterior funiculus at the Th2 level. CSF analysis showed the following results: leukocyte count, 109/mm3 , and protein level, 79 mg/dl, as well as negativity for VZV PCR, elevated titer levels for anti-VZV IgM and IgG, and increased IgG index. Although she was treated with a combination of acyclovir and steroid pulse therapy, her weakness in the right lower limb did not improve. In this case, because the posterior funiculus circulating from the posterior spinal artery was not involved, the incomplete Brown-Séquard syndrome may have been caused by spinal cord infarction due to VZV vasculitis of the anterior spinal artery.

#### **8. Postherpetic neuralgia**

Although most cases of acute herpes zoster are self-limited, about 10–15% of patients with herpes zoster will develop postherpetic neuralgia (PHN) [32], particularly in older adults [33]. Immunosuppressed patients have a higher incidence of PHN. PHN refers to pain persisting for months to years after the resolution of the

**39**

disorders.

*Neurologic Complications of Varicella-Zoster Virus Infection*

available for prevention of acute zoster and PHN [38, 39].

rash. Sensory symptoms can include pain, numbness, dysesthesias, and allodynia (pain precipitated by movement) in the affected dermatome. And these symptoms may be severe enough to restrict sleep, appetite, or daily activities. The diagnosis of PHN is clear-cut and could be made if those sensory symptoms including pain persist beyond 4 months in the same distribution as a preceding episode of acute herpes zoster [34]. Gabapentin, pregabalin, tricyclic antidepressants, and opioids are generally the first-line drugs for the treatment of PHN [35–37]. Vaccines are also

For the diagnosis of CNS infection caused by VZV, the detection of VZV DNA with PCR using CSF is necessary [40–42]. However, a negative VZV DNA result does not rule out VZV infection, and particularly, PCR examination after the initiation of antiviral treatment will likely turn out negative. Thus, testing should be conducted using CSF before the antiviral treatment. When measuring anti-VZV antibodies, a significant increase of the anti-VZV antibody titer in CSF over the course of the illness or findings suggesting the production of intrathecal antibody [serum/CSF antibody ratio ≤ 20 or antibody titer index = (CSF antibody/serum

antibody)/(CSF albumin/serum albumin ≥ 2)] should be confirmed.

Antiviral therapy with intravenous acyclovir (10 mg/kg intravenous every 8 hours) should be initiated as soon as the diagnosis is considered [43]. Although the prognosis of meningitis is good, encephalitis and myelitis often result in

sequelae, and a delay in the initiation of acyclovir treatment leads to poor prognosis. Therefore, if CNS infection caused by VZV is suspected based on clinical symptoms as well as CSF examination and imaging findings, the administration of acyclovir must be immediately initiated. According to a recent study from the UK, some causative pathogens were identified in 42% of acute encephalitis cases, of which HSV or VZV was identified in one-fourth of the cases. Thus, the administration of acyclovir should be immediately initiated if encephalitis is clinically suspected, and then, acyclovir should be administered for 2 weeks in an immunocompetent host and for 3 weeks in an immunosuppressive host if encephalitis caused by HSV or VZV is confirmed [5]. In CNS infection caused by VZV, the standard administration period is similar. There is no evidence showing the therapeutic effect of adjunctive corticosteroid use. However, corticosteroids suppress the inflammatory response accompanied by cytotoxicity due to the host immune response to viral infection, and in cases of encephalitis/vasculitis, myelitis, and cranial polyneuropathy, the adjunctive administration of dexamethasone or steroid pulse therapy with acyclovir

VZV causes the diverse spectrum of neurologic complications: aseptic meningitis, encephalitis, cerebral infarction associated with granulomatous vasculitis, myelitis, and cranial polyneuropathy. Clinicians should be aware of the neurologic complications of VZV, because early acyclovir therapy is necessary for these

*DOI: http://dx.doi.org/10.5772/intechopen.83036*

**9. Diagnosis**

**10. Therapy**

is recommended.

**11. Conclusions**

*Neurologic Complications of Varicella-Zoster Virus Infection DOI: http://dx.doi.org/10.5772/intechopen.83036*

rash. Sensory symptoms can include pain, numbness, dysesthesias, and allodynia (pain precipitated by movement) in the affected dermatome. And these symptoms may be severe enough to restrict sleep, appetite, or daily activities. The diagnosis of PHN is clear-cut and could be made if those sensory symptoms including pain persist beyond 4 months in the same distribution as a preceding episode of acute herpes zoster [34]. Gabapentin, pregabalin, tricyclic antidepressants, and opioids are generally the first-line drugs for the treatment of PHN [35–37]. Vaccines are also available for prevention of acute zoster and PHN [38, 39].

### **9. Diagnosis**

*Human Herpesvirus Infection - Biological Features, Transmission, Symptoms, Diagnosis...*

in the dorsal root nerve, and these findings indicate myeloradiculitis.

be considered another mechanism.

**7.1 Case 7: myelitis**

dorsal root.

**7.2 Case 8: myelitis**

**8. Postherpetic neuralgia**

VZV myelitis is a rare clinical manifestation. However, Brown-Séquard syndrome and transverse myelopathy may occur as a complication of herpes zoster infection [6, 7, 29–31]. Previous reports revealed that myelitis occurred in elderly or immunocompromised patients, such as those with HIV infection, and this condition often had severe sequelae such as motor paralysis [6, 7]. MRI shows low to equal signal intensity on T1-weighted images and high signal intensity on T2-weighted images, and sometimes, contrast enhancement can be observed as spinal cord lesions. In addition, MRI enhancement may be observed not only in the lesions in the spinal cord but also in the meninges around the spinal cord as well as

Myelitis is often characterized by myelopathy at a level consistent with the spinal segment affected by herpes zoster. As a pathogenesis of this condition, reactivated VZV in the dorsal root ganglion of the spinal cord directly invades the spinal cord from the dorsal root nerve, resulting in myelitis [6, 7]. Moreover, spinal cord lesions are caused by vasculopathy, such as damage to the anterior spinal artery due to vasculitis, similar to cerebral infarction after herpes zoster infection, and this may

The patient was a 60-year-old man with right lower extremity paralysis and sensory disturbance of the right trunk and lower extremity who was diagnosed with VZV myelitis based on CSF examination. MRI of the spinal cord showed a highsignal lesion in the right posterior funiculus at the thoracic vertebral level of Th6 and Th7, which should indicate that VZV directly invaded the spinal cord from the

An 87-year-old woman developed weakness of the right lower limb 2 days after developing herpes zoster lesions in the right side of the chest. Neurological examination revealed a spastic palsy in the right lower limb and loss of pain and temperature sensation in the left side to T6. However, vibration and position senses were not impaired in both sides. Thus, the patient presented with incomplete Brown-Séquard syndrome. Spinal T2-weighted MRI images showed a high-intensity lesion in the right side of the spinal cord except at the posterior funiculus at the Th2 level. CSF analysis

as well as negativity for VZV PCR, elevated titer levels for anti-VZV IgM and IgG, and increased IgG index. Although she was treated with a combination of acyclovir and steroid pulse therapy, her weakness in the right lower limb did not improve. In this case, because the posterior funiculus circulating from the posterior spinal artery was not involved, the incomplete Brown-Séquard syndrome may have been caused by

Although most cases of acute herpes zoster are self-limited, about 10–15% of patients with herpes zoster will develop postherpetic neuralgia (PHN) [32], particularly in older adults [33]. Immunosuppressed patients have a higher incidence of PHN. PHN refers to pain persisting for months to years after the resolution of the

spinal cord infarction due to VZV vasculitis of the anterior spinal artery.

, and protein level, 79 mg/dl,

showed the following results: leukocyte count, 109/mm3

**7. Myelitis**

**38**

For the diagnosis of CNS infection caused by VZV, the detection of VZV DNA with PCR using CSF is necessary [40–42]. However, a negative VZV DNA result does not rule out VZV infection, and particularly, PCR examination after the initiation of antiviral treatment will likely turn out negative. Thus, testing should be conducted using CSF before the antiviral treatment. When measuring anti-VZV antibodies, a significant increase of the anti-VZV antibody titer in CSF over the course of the illness or findings suggesting the production of intrathecal antibody [serum/CSF antibody ratio ≤ 20 or antibody titer index = (CSF antibody/serum antibody)/(CSF albumin/serum albumin ≥ 2)] should be confirmed.

#### **10. Therapy**

Antiviral therapy with intravenous acyclovir (10 mg/kg intravenous every 8 hours) should be initiated as soon as the diagnosis is considered [43]. Although the prognosis of meningitis is good, encephalitis and myelitis often result in sequelae, and a delay in the initiation of acyclovir treatment leads to poor prognosis. Therefore, if CNS infection caused by VZV is suspected based on clinical symptoms as well as CSF examination and imaging findings, the administration of acyclovir must be immediately initiated. According to a recent study from the UK, some causative pathogens were identified in 42% of acute encephalitis cases, of which HSV or VZV was identified in one-fourth of the cases. Thus, the administration of acyclovir should be immediately initiated if encephalitis is clinically suspected, and then, acyclovir should be administered for 2 weeks in an immunocompetent host and for 3 weeks in an immunosuppressive host if encephalitis caused by HSV or VZV is confirmed [5]. In CNS infection caused by VZV, the standard administration period is similar. There is no evidence showing the therapeutic effect of adjunctive corticosteroid use. However, corticosteroids suppress the inflammatory response accompanied by cytotoxicity due to the host immune response to viral infection, and in cases of encephalitis/vasculitis, myelitis, and cranial polyneuropathy, the adjunctive administration of dexamethasone or steroid pulse therapy with acyclovir is recommended.

#### **11. Conclusions**

VZV causes the diverse spectrum of neurologic complications: aseptic meningitis, encephalitis, cerebral infarction associated with granulomatous vasculitis, myelitis, and cranial polyneuropathy. Clinicians should be aware of the neurologic complications of VZV, because early acyclovir therapy is necessary for these disorders.
