A 33-year-old man was referred to the emergency department and admitted (day 1) to a general hospital for acute onset of isolated diplopia six hours prior. Seven days prior to admission, he developed an unspecific syndrome, characterized by mild headache, generalised myalgia, vomiting and nausea without fever. Neurological examination was unremarkable except for vertical and cross diplopia at left eye suggesting an isolated fourth nerve palsy. Ocular examination including visual field and fundoscope assessment were normal and no pathological findings were observed on Brain CT Scan.
Cerebro-spinal fluid (CSF) analysis performed in the same day showed pleocytosis (white blood cells count of 969/mm3 with normal value < 2/mm3, 80% lymphocytes), proteins 188 mg/dl (normal value 8–32 mg/dl) and glucose 51 mg/dl (normal value 40–70 mg/dl), with a blood glucose of 111 mg/dl (normal value 70-110 mmg/dl). Gram stain was negative. The day after, in the suspicion of a viral encephalitis, antiviral therapy with intravenous acyclovir was started at the dose of 10 mg/kg every 8 hours and the patient was referred to our Infectious Diseases hospital.
At admission in our hospital (day 2) his clinical condition was unchanged. We continued antiviral therapy and added anti microbial therapy with ceftriaxone 2 grams twice a day, and ampicillin 2 grams 6 times a day.
Diplopia persisted despite treatment, so on day 4 a second lumbar puncture was performed. The CSF analysis showed 200 WBC/mm3 (normal value < 2/mm3), protein 200 mg/dl (normal value 8–32 mg/dl) and glucose 56 mg/dl (normal value 40–70 mg/dl), with a blood glucose of 94 mg/dl (normal value 70-110 mmg/dl). Routine tests were normal. Magnetic Resonance Imaging (MRI) of the brain showed right sphenoid sinusitis only. Chest X-ray was normal.
The agents most frequently responsible of meningo-encephalitis were investigated: serological tests for VZV, cytomegalovirus, herpes simplex virus 1–2, Epstein Barr virus, measles virus, mumps virus, rubella virus, adenovirus, enterovirus, influenza and parainfluenza virus, reovirus, respiratory syncytial virus, tick-borne encephalitis agents, West Nile virus, Toscana virus were all negative. A PCR performed on pharyngeal and rectal swab resulted negative for enterovirus, adenovirus and respiratory viruses. Additional examinations included serology for Brucella, Listeria, Treponema, Coxiella, Mycoplasma, Chlamydia, Borrelia, Leptospira, Criptococcus antigen, Quantiferon, HIV antigen and antibody test, Legionella and pneumococcal urinary antigen, autoantibodies. All these tests resulted negative.
A set of quantitative real-time PCR performed on CSF was negative for herpes simplex virus 1–2, human herpes virus 6, cytomegalovirus, Epstein Barr virus, enteroviruses, measles virus, mumps virus and M. tubercolosis, while a quantitative real-time PCR (HSV-VZV R-Gene Quantification Test, Biomerieux®) resulted positive for VZV-DNA, with a viral load of 30360 copies/ml.
On day 8 after initial admission, before a definitive diagnosis was established, corticosteroid therapy with oral prednisone was started at the initial dose of 50 mg once daily and then at tapering dosages over a 40 days course, as suggested by neurologist consultant. Partial improvement of diplopia was observed after three days. Antibiotics were stopped on day 12, while acyclovir was continued up to day 14. The diplopia progressively improved, and the patient was discharged on day 23. Forty-five days later, the patient reported the complete disappearance of diplopia. Full resolution of oculo-motor impairment was evidenced by an Hess-Lancaster test performed 3 months later.