In November 2008, a 45-year-old woman developed confusion, an expressive aphasia and a mild spastic paraparesis with left-sided hyperreflexia. Brain magnetic resonance imaging (MRI) revealed bilateral non-enhancing cortical and subcortical T2 hyperintensities () as well as leptomeningeal enhancement. The CSF contained 26 white blood cells (WBCs), 100% mononuclear cells (MNCs), 387 RBCs, protein 140 mg%, and glucose 58 mg%. CSF IgG was 24.1 mg%, which constituted 17.2% of total CSF protein (normal 3-13%), and there were no oligoclonal bands. PCR for VZV, herpes simplex virus (HSV-1 and HSV-2) and human herpesvirus-6 DNA was negative. No studies for antiviral antibodies in CSF were performed. CSF angiotensin-converting enzyme level was normal. Six days later, the CSF contained 24 WBCs, 100% MNCs, 2 RBCs, protein 83 mg%, and glucose 53 mg%. PCR was again negative for VZV, types HSV-1 and -2 DNA. CSF paraneoplastic antibody panel, VDRL and cytology were negative. CSF IgG was 14.4 mg%, which constituted 17.3% of total CSF protein. Brain biopsy of the gray matter, white matter and meninges showed no evidence of inflammation, granulomas or vasculitis. She was treated with acyclovir, 10 mg/kg intravenously 3 times daily for two days and oral prednisone 40 mg daily for three months, but when MRI and PCR revealed lack of evidence of HSV encephalitis, the acyclovir was discontinued. At discharge, neurological signs consisted of mild expressive aphasia, mild paraparesis, increased deep tendon reflexes (DTRs) in the legs and decreased sensation to all modalities in the right leg. In January 2009, brain MRI revealed decreased leptomeningeal enhancement along with a new T2 hyperintense signal in the periaqueductal gray matter. In March 2009, neurological signs consisted of mildly impaired recall, mild right leg weakness and diffuse hyperreflexia.
Fig. 1 MRI brain, T2 Flair axial. (A) Posterior hemispheric swelling and increased signal involving the left medial-occipital gyrus. (B) Gyriform swelling and increased T2 signal involving the right parasagittal parietal and occipital gyri. Left frontal lobe (more ...)
On 6-30-09, the patient developed acute low back pain. Neurological examination revealed marked tenderness to light palpation along the entire spine, but no other signs. MRI of the thoracic and lumbar spine showed an enhancing T2-hyperintense lesion from T2-11 and mild spinal cord swelling. Throughout the day, she developed increasing leg weakness and urinary retention. Neurological examination revealed a spastic paraparesis, sensory loss to all modalities from T3-11 on the left, hyperactive DTRs in the legs and a left extensor plantar response. The CSF contained 2978 WBCs, 90% PMNs, 10% MNCs, 678 RBCs, protein 247 mg%, and glucose 47 mg%. CSF bacterial cultures were negative. PCR for VZV, cytomegalovirus (CMV), HSV-1 and -2 DNA, and for enterovirus and West Nile virus was negative. She was treated with vancomycin, 1000 mg intravenously twice daily and ceftriaxone 2000 mg intravenously twice daily for 6 days and methylprednisolone 1000 mg intravenously daily for 3 days. Her back pain decreased in a few days, but her neurological deficits remained. On 7-3-09, the CSF contained 95 WBCs (22% PMNs, 72% MNCs, 5% eosinophils, 1% basophils), 24 RBCs, protein 74 mg%, and glucose 51 mg%. Bacterial cultures were negative. She was discharged on oral prednisone 60 mg daily and intermittent straight catheterization.
On 7-6-09, the serum from 6-30-09 was reported to contain anti-VZV IgM antibody, and she was immediately treated with acyclovir, 10 mg/kg intravenously three times daily for 2 weeks, and oral prednisone, 60 mg daily for 2 days. The CSF of 6-30-09 was also later reported to contain anti-VZV IgG antibody, but not anti-HSV IgG or anti-CMV IgG antibody, and the serum/CSF ratio of anti-VZV IgG antibody was reduced (ratio 2.6:1) compared to albumin (ratio 89:1) and total IgG (ratio 151:1), consistent with intrathecal synthesis of anti-VZV IgG antibody. On 8-11-09, the neurological examination was normal.
On 8-20-09, she felt her “legs give out” and complained of diffuse numbness as well as neck pain radiating down the spine. Neurological examination revealed a decreased attention span, word-finding difficulties, a spastic paraplegia and extensor plantar responses. On 8-24-09, a brain MRI showed a new enhancing T2 signal in the meninges over the left superior frontal gyrus, and MRI of the cervical and thoracic spine revealed a diffuse T2 hyperintensity involving the entire cervical spine and the thoracic spine from T1-8 (). The CSF was xanthochromic and contained 48 WBC, 49% PMNs, 51% MNCs, 990 RBCs, protein 283 mg% and glucose 46 mg%. Bacterial cultures were negative, and CSF neuromyelitis optica antibody was negative. Although VZV PCR was negative, the CSF contained anti-VZV IgG antibody, but not anti-HSV IgG antibody. The serum/CSF ratio of anti-VZV IgG antibody was reduced (ratio 1.32:1) compared to albumin (ratio 19:1) and total IgG (ratio 65:1). She was treated with acyclovir 10 mg/kg intravenously three times daily for 3 weeks, methylprednisolone 1000 mg intravenously daily for 2 days and valacyclovir 1 gm daily for 2 months. Examination at discharge revealed a flaccid paralysis in both legs, decreased sensation to all modalities below T3, hyperreflexia in the arms with clonus at the wrists and bilateral extensor plantar responses. On 9-17-09, the CSF contained 8 WBCs, 100% MNCs, 29 RBCs, protein 94 mg% and glucose 46 mg%. PCR for VZV DNA was negative; the CSF contained anti-VZV IgG antibody, but not anti-HSV IgG antibody, and the serum/CSF ratio of anti-VZV IgG antibody was reduced (ratio 2.5:1) compared to albumin (ratio 68:1) and total IgG (ratio 141:1).
MRI cervical spine. (A) Sagittal T2 fast-recovery fast-spin echo sequence: abnormal T2 hyperintense signal and expansion involving the medulla and entire cervical spinal cord. (B) Sagittal T1 Flair post-contrast: abnormal leptomeningeal enhancement.
On 10-6-09, she developed bilateral arm numbness and weakness. Neurological examination revealed a mild receptive aphasia and spastic weakness of both arms; the lower extremity signs were unchanged. The CSF contained 6 WBCs, 98% MNCs, 0 RBCs, protein 136 mg% and glucose 51 mg%. PCR for VZV and CMV was negative; the CSF again contained anti-VZV IgG antibody, but not anti-HSV or CMV IgG antibody, and the serum/CSF ratio of anti-VZV IgG antibody was 2.2:1. Brain MRI showed increased signal involving the corticospinal tracts and ventral cervico-medullary junction. MRI of the cervical and thoracic spine revealed less spinal cord swelling and leptomeningeal enhancement. She was treated with acyclovir 10 mg/kg intravenously three times daily for 2 weeks and valacyclovir 1 gram twice daily for 2 months. summarizes the CSF findings for this patient.
In 1989, at age 25, the patient had had a monophasic episode of demyelinating disease involving the brain and brainstem. On 7-1-89, a brain biopsy identified an acute inflammatory demyelinating lesion with relative axonal sparing. The inflammatory response consisted of perivascular lymphocytes, plasma cells and plasmablasts. There was a moderate reactive gliosis and monocytic plasmocytic infiltration into parenchyma with focal clustering of foamy macrophages. No further episodes of demyelinative disease ever occurred, MRI scanning 20 years later revealed no multiple sclerosis (MS) plaques, and the CSF did not contain oligoclonal bands. Thus, her neurological disease in 1989 was most likely acute disseminated encephalomyelitis. While VZV infection can be associated with disseminated encephalomyelitis [2
], our patient's monophasic episode was not preceded by varicella or zoster. The patient was lost to follow-up, but reported the onset of generalized tonic-clonic seizures in 1995.