Varicella-zoster encephalitis – a case history

1. Varicella-zoster encephalitis – a case history Southern Neurology

2. Case history • H.J. • 63 y.o.male • Presents August ’03 with 2 week history of somnolence, poor concentration, increasing generalised weakness, intermittent headaches, nausea and visual hallucinations • 1 week prior to onset of symptoms had right T1 HZ infection. Given valacyclovir but ceased after 2 days due to nausea

3. Past medical history • Diabetes mellitus since age 40 years. Insulin requiring > 5 years. Diabetic nephropathy – proteinuria 0.18 g/day; serum creatinine May ’03 of 140. • Chronic inflammatory demyelinating polyneuropathy ~ 5 years. Treated with IV immunoglobulin and for past 6 months mycophenylate. • IHD – AMI and CABGs 10 years ago • Hypertension • Dyslipidaemia

4. Medications • Mixtard 30/70 70 U mane; protaphane 40 U nocte • Lopid 600 mg bd • Lasix 125 mg mane; Aldactone 25 mg bd • Captopril 25 mg bd • Magnesium 500 mg nocte • Transiderm nitro patch • Solprin 75 mg mane • Nexium 40 mg mane

5. Clinical examination • Afebrile but dehydrated and hypotensive • Somnolent (± drowsy) and but easily roused • Orientated to time, place and person • HS dual, no murmurs; chest clear • Signs of peripheral neuropathy with distal weakness grade 3-4/5 upper and lower limbs, areflexia and distal glove and stocking sensory loss

6. Initial investigations • WCC 9.6, Hb 103, Plat 310 • Na 132, K 5.2, Urea 40, Creat 309 • HbA1c 8.8% • CXR clear • ECG SR, no ischaemic changes • MSU no growth • CT brain normal

7. Differential diagnosis • ? Diagnosis • ? Further investigations

8. Further investigations and treatment • Lumbar puncture – successful after several attempts (patient weighed 120 kg). CSF protein 0.54, Glc 3.0, cell count 90 lymphocytes, 2 polymorphs, 1 RBC. • Commenced IV acyclovir initially 1 g bd but changed subsequently to 750 mg tds. • Lasix, aldactone, captopril and dilatrend all temporarily ceased. • Mycophenylate withdrawn • CSF Varicella-Zoster PCR positive

9. Clinical progress • Improved dramatically within 72 hours. • Treated with IV acyclovir for 10 days followed by oral valacyclovir 1 g tds for 14 days. • Discharged home at day 10. • Readmitted Nov’03 with 1 week history of increasing somnolence, confusion, hallucinations. Clinically dehydrated, serum urea 28, creatinine 239. • CT brain normal • Rpt LP < 1 WBC, CSF protein 0.43, Glc 5.1, VZ PCR neg • Improved with rehydration and sent home

10. Varicella-zoster: a re-emerging infection • A recent Finnish study (J Neurovirol 2001; 7: 400-8), using PCR to detect various viruses in the CSF of over 3000 patients who had CNS infections including encephalitis, meningitis and myelitis ,found that VZ virus was the most frequently detected at 29% with HSV and enetroviruses accounting for 11% of cases each, and influenza A virus found in 7% of cases.

11. VZ virus reactivation in the CNS/PNS • Latent in cranial nerve and dorsal root ganglia. • CNS - myelitis, large vessel encephalitis/granulomatous arteritis, small vessel encephalitis, menigo-encephalitis and ventriculitis. • PNS - herpes zoster ± post-herpetic neuralgia, cranial mononeuropathy (eg Bell’s palsy) or polyneuropathy, post-infectious generalised polyneuritis (GBS). • All may occur with or without cutaneous manifestations.

12. Reactivation: zoster (shingles, ganglionitis) • In U.S.A., 300,000-850,000 cases per year. • 8-10 fold increased frequency in ages > 60 years compared to < 60 years • Incidence of recurrent zoster < 5% • Thoracic zoster most common followed by lesion of the face, most often opthalmic division of trigeminal nerve. Zoster oticus and peripheral facial weakness constitutes Ramsay-Hunt syndrome. • Zoster cranial neuropathy may develop weeks after acute infection due to slow spread along afferent fibres to small vessels

13. VZ encephalitis in immuno-compromised patients (Neurology 1999; 52: 193-95) • Two patients with AIDS and one with HD who developed headache in 2 patients, seizures in 2 patients, and hemiparesis and myelopathy in 1 patient. The two AIDS patients had HZ 4-8 months prior and the HD patient had no history of cutaneous zoster. • Initial CTs normal but MRIs showed well defined spherical, nonenhancing subcortical lesions with progression to coalescence, cavitation, haemorrhage and enhancement. • Histologically, demyelination, necrosis, with accompanying astrogliosis and macrophage infiltration.

14. (A) Unenhanced T1-weighted MR image shows gyral hemorrhage and clusters of spherical hypointense lesions along the right frontoparietal cortical and subcortical areas. (B) Enhanced T1-weighted MR image shows homogeneous and ring-enhancing lesions. (C) Proton density MR image reveals spherical and clustered hyperintense lesions. Additional lesions are seen in the right frontal subcortical white matter that are not evident on the T1-weighted images

15. Focal cavitation in the digitate white matter and gray-white junction. Note the spherical lesions in the adjacent subcortical white matter. These lesions correspond to the focal lesions seen earlier on MRI.

16. (A) Unilateral left hyperperfusion in a patient with herpes zoster encephalitis imaged 5 days after onset of symptoms. (B) Unilateral hypoperfusion in a patient with focal encephalitis 3 months after onset. (C) Bilateral frontal hypoperfusion in a patient with varicella-zoster encephalitis 4 days after onset. D) Normal SPECT scan in a patient with encephalitis 3 days after onset

17. VZ encephalitis without rash • Typical picture is in immuno-compromised patient who develops acute CNS disease or may have a history of zoster weeks to months later or recurrent zoster. CNS disease more often develops in the absence of acute evidence of zoster. • Encephalitis is ususally ‘small vessel’ type and the disease is usually protracted. • Acute VZ myelitis and aspetic meningitis may also occur in the absence of a rash. • ? Recent study suggests aetiology in up to 29% of cases of Bell’s palsy