Abstract
We present the case of a 48-year-old HIV-positive man, who developed acute onset of pain in both upper limbs associated with proximal weakness and distal paraesthesia. Eight weeks prior to this presentation he had had varicella zoster affecting his right S1 dermatome. CD4 count was 355 cells/mm3 and he was antiretroviral therapy (ART) naive. Power was 0/5 proximally and 4/5 distally in the upper limbs. Reflexes were absent and there was sensory loss in the C5, C6 and T1 dermatomes. Cerebrospinal fluid (CSF) examination showed a lymphocytosis with low glucose; however, CSF Mycobacterium tuberculosis (TB), and herpes simplex virus polymerase chain reaction (HSV PCR) were negative as was syphilis serology. Electromyography showed marked motor axonal loss. Magnetic resonance imaging (MRI) did not show any cervical spinal lesion. Varicella zoster virus (VZV) PCR was positive in the CSF. He was treated with high-dose intravenous aciclovir with good resolution of his syndrome over time and was commenced on ART. We believe this to be the first case report of varicella reactivation causing bilateral neuralgic amyotrophy in an HIV-positive patient.
Keywords
CASE REPORT
A 48-year-old, HIV-positive man presented with a two-week history of bilateral shoulder pain, proximal weakness and distal paraesthesia.
His symptoms began in his right shoulder with sudden onset of pain, which spread to the entire right upper limb within 24 hours, and the left shoulder and arm within 48 hours. It was associated with inability to elevate his arms above his shoulder and numbness bilaterally from his shoulder to his hands with tingling in the lateral four digits. He had no weight loss, anorexia or night sweats.
His CD4 count was 355 cells/mm3, one month prior to this acute presentation. He was antiretroviral therapy (ART) naive. Treponemal serology was negative. He had had a recent episode of herpes zoster affecting his right S1 dermatome eight weeks prior to this presentation.
Medical Research Council grading of power was 0/5 proximally and 4/5 distally in the upper limbs. Tone was reduced and reflexes were absent in the upper limbs. He had sensory loss bilaterally in the C5, C6 and T1 dermatomes. There were no signs of meningism and there was no dermatological evidence of active varicella zoster virus (VZV) infection.
A lumbar puncture showed a clear, colourless, lymphocytic cerebrospinal fluid (CSF) with low glucose. Gram stain, Ziehl-Neelsen (ZN) stain, Mycobacterium tuberculosis (TB) polymerase chain reaction (PCR) and culture, cryptococcal antigen and syphilis serology were all negative. The CSF was PCR-negative for herpes simplex virus, cytomegalovirus, Epstein–Barr and enterovirus, but was VZV PCR-positive. The electromyography (EMG) and nerve conduction studies showed marked motor axonal loss in the left C5, C6 and, to a lesser extent, C7 myotomes and in the right C5 and C7 myotomes. Not all C5-innervated muscles were involved to the same extent in the right upper limb. Magnetic resonance imaging (MRI) of his cervical spine showed mild cervical spondylosis but no evidence of cord compression or nerve route impingement.
This clinical constellation was consistent with bilateral brachial neuritis, also known as Parsonage−Turner syndrome, associated with a recent history of herpes zoster.
He completed a 21-day course of intravenous aciclovir and was commenced on ART with tenofovir, emtricitabine and efavirenz. He was treated with gabapentin and amitriptyline for pain. He tolerated ART well and was discharged on prophylactic valaciclovir. He continued to improve clinically and returned to work within one year.
DISCUSSION
Parsonage−Turner syndrome, or neuralgic amyotrophy, was first described in 1943, when Spillane 1 described a series of patients with localized neuritis of the shoulder girdle. Parsonage and Turner 2 subsequently reported on a series of 136 patients with a similar condition in 1948, which they named shoulder girdle syndrome or neuralgic syndrome. The condition has since been referred to as Parsonage−Turner syndrome.
It is characterized by the acute onset of severe shoulder pain followed by flaccid paralysis of shoulder muscles within days. The incidence has been estimated at 1–2 in 100,000. The peak rate is between the ages of 30 and 50, with a slight male predominance. It occurs in both a hereditary and an idiopathic form. The inherited form is autosomal dominant and is linked to mutations in the SEPT9 gene on chromosome 17, although their exact role in this disease is unknown. It presents at a younger age and is characterized by recurrent episodes.
The aetiology of the idiopathic form is unclear, but it is thought to be immune mediated. There is axonopathy with Wallerian degeneration, but proximal conduction block has also been demonstrated. Although the aetiology is unknown, it has been linked to many antecedent events. In a review of 246 patients with neuralgic amyotrophy conducted in the Netherlands, infection was the most common antecedent event, followed by exercise, surgery, pregnancy, vaccination, stress and trauma. 3
Parsonage−Turner syndrome has been described in acute HIV seroconversion and HIV should always be borne in mind when a patient presents with neuralgic amyotrophy. 4,5 Diagnosis is supported by CSF, EMG and MRI.
The EMG usually reveals acute denervation resulting from an axonal neuropathy. Proximal conduction block suggestive of focal demyelination has also been described. Characteristic of Parsonage−Turner syndrome is the fact that there is a discrepancy for muscle wasting and denervation between muscles innervated by the same nerve. 6 MRI may be normal in patients with Parsonage−Turner syndrome but may also show muscular high T2 signal intensity abnormality that is consistent with involvement of a peripheral nerve or nerves from the brachial plexus. This is not diagnostic, however, and may also occur in trauma or nerve entrapment. 7
Prognosis is generally good with about 80% achieving functional recovery within two years and 90% by three years. The prognosis is less favourable with bilateral disease. However, our patient made a full recovery returning to full-time employment within years. Treatment is usually symptomatic pain control with physiotherapy for rehabilitation. Immunosuppressive therapy has not been shown to be of any definite benefit.
Our patient had been diagnosed HIV-positive four years prior to the episode of neuralgic amyotrophy and was not on ART. Mycobacterial disease as a differential diagnosis must be considered but ZN staining, TB PCR and culture were all negative. Although spinal mycobacterial disease can occur at any CD4 count, it is more likely with a CD4 count of less than 200. 8 Also spinal TB is more likely to affect the lower thoracic and lumbar spine than the cervical spine. 9 MRI in this case showed only cervical spondylosis but no evidence of vertebral collapse or granulomatous infiltration, which would be more likely in spinal TB. There was no preceding history of trauma. Given the acute onset of severe pain and weakness, lack of a structural cause on MRI, CSF positive for VZV and excellent response to ART and commencement of ART, Parsonage− Turner syndrome is the most likely diagnosis. We believe that VZV reactivation was the antecedent cause for his neuralgic amyotrophy. The association between VZV and brachial plexitis has been noted in the literature previously, 10 but we believe this to be the first case report of VZV reactivation causing bilateral neuralgic amyotrophy in an HIV-positive patient.