Age: 1.0
Sex: M
Vaccine: VARCEL
Symptoms: Anal sphincter atony, Anorectal manometry, Anti-aquaporin-4 antibody negative, Anti-ganglioside antibody negative, Anti-muscle specific kinase antibody
Clinical narrative: VZV vaccine reactivation/reactivation of vaccine varicella causing a shingles like picture and subsequent demyelinating polyneuropathy predominantly affecting the Mueller muscles in the eyes and the bladder and distal bowel autonomic innervation; reactivation of vaccine varicella causing a shingles like picture and subsequent demyelinating polyneuropathy predominantly affecting the Mueller muscles in the eyes and the bladder and distal bowel autonomic innervation; rare presentation of neurological manifestations of reactivation of varicella zoster virus in a fully vaccinated child; This literature marketed report has been received from the authors of a published literature article, entitled as stated below, and refers to a 10-year old-male patient with attention deficit hyperactivity disorder (ADHD). His concomitant therapies included a home medication methylphenidate, and it was reported that there were no recent changes to it. The patient's medical history included a mild upper respiratory infection 1 week prior to the onset of the symptoms.  On an unknown date, at the age of 1 year, the patient was vaccinated with the first dose of varicella virus vaccine live (oka/merck) (manufacturer unknown) (dose, route and site of administration, lot # and expiration date were not reported) for prophylaxis. On an unknown date, at the age of 5 years, the patient was vaccinated with the second dose of varicella virus vaccine live (oka/merck) (manufacturer unknown) (dose, route and site of administration, lot # and expiration date were not reported) for prophylaxis.  On an unknown date, the patient experienced a bilateral eyelid drooping, intermittent double vision and fatigue, and after 2 weeks from onset of these symptoms, he presented to the authors' institution. The eyelid droop was acute in onset. The double vision was transient and had resolved when the patient was evaluated in neurology. The patient also complained of an intermittent burning/itching sensation to the left forearm. He had mild changes in appetite, but no changes to urine or stool output, initially. The patient was afebrile and did not have any recent history of fever, diarrhea, abdominal pain, or head trauma. In the Emergency Department (ED), the neurological examination revealed reactive pupils and normal extraocular movements; however the patient had bilateral ptosis. The rest of the cranial nerves were normal. Strength, tone and reflexes were normal and sensory examination was normal. No rash was evident. His weight was 30 kg. Initial investigation included computed tomography (CT) of the head and magnetic resonance imaging (MRI) of the brain with and without contrast that were normal. Cerebrospinal fluid (CSF) studies including Enterovirus Polymerase Chain Reaction (PCR), Oligoclonal bands, Myelin basic protein and routine CSF analysis were obtained. Serum acetylcholine binding antibodies and anti-muscle specific kinase (MuSK) IgG antibodies were also drawn (no results were provided). An ice pack test was performed at bedside which was negative. The patient was treated as ocular myasthenia gravis due to isolated bilateral ptosis and was sent home with pyridostigmine 30 mg every 6 hours, prednisone 15 mg every other day and famotidine. The patient returned 2 days after discharge with complaints of eye pain following outpatient ocular dilation for ophthalmology examination and bilateral lower extremity pain. He received 3 doses of prednisone at 15 mg prior to his admission. He complained of persistent burning and itching of his left forearm, persistent bilateral ptosis and fatigue. Since he did not respond to the pyridostigmine and steroids, acetylcholine receptor antibodies were negative, and he was now having prominent sensory symptoms, Guillain-Barre Syndrome variant such as Miller Fischer was considered in the differential diagnosis and he was admitted for treatment with intravenous immunoglobulins (IVIG). During this admission, the patient developed mild ataxia and severe constipation. Anal manometry showed significantly decreased sensation suggesting a neuronal process. Simultaneously, he developed urinary retention with a complete loss of bladder sensation requiring intermittent catheterization. Physical examination showed a loss of anal wink, but did not reveal any loss of deep tendon reflexes. The strength in upper and lower extremities continued to be normal, reflexes were normal and there was no evidence of sensory loss. He now developed a pruritic rash on his left extensor elbow that spread to upper back and anterior chest over a course of a week. The rash initially was excoriated in appearance, but later became papular/vesicular in characteristic. He was started on gabapentin for bilateral leg pain. Extensive evaluation throughout both admissions, including CT imaging of head, MRI of brain and total spine, MRI of lumbar spine (twice) and chest X-ray were normal. CSF studies were normal aside from 2+oligoclonal bands. Antibody testing including MuSK, Ganglioside (GQ1B), anti-low density lipoprotein receptor- related protein antibodies (LRP4), extractable nuclear antigen 7 (ENA7), aquaporin 4 (neuromyelitis optica), myelin oligodendrocyte glycoprotein (MOG) and paraneoplastic antibodies were negative. A mitochondrial gene panel was inconclusive. Electromyography (EMG) and nerve conduction velocity (NCV) studies were performed twice identifying decreased amplitude over the bilateral facial nerves and absence of F waves from the bilateral peroneal nerves. Rheumatology and infectious disease were consulted due to the rash. The rash was consistent with reactivation of varicella in the C8-T1 and C5-C6 dermatomes. The differential was reactivation of vaccine varicella causing a shingles like picture (varicella post vaccine) and subsequent demyelinating polyneuropathy predominantly affecting the Mueller muscles in the eyes and the bladder and distal bowel autonomic innervation. The patient was started on intravenous acyclovir and a Zoster IgM was obtained. Ptosis completely resolved by the 4th day of acyclovir treatment with improvement in fatigue and ataxia. However, the urinary retention and constipation persisted. Given the absent F waves and presence of oligoclonal bands that are often a marker of acute demyelinating illness in younger children as well as persistence of complete bladder and distal bowel paralysis, he received 3 cycles of plasmapheresis as immunotherapy. Prior to discharge, his ptosis had fully resolved, ambulation was back to baseline and urinary retention and constipation had improved. During follow up at 4 months, he had regained partial sensation in his bladder and did not require urinary catheterization to urinate. Bowel sensation has also improved and he was able to defecate with some assistance of a laxative. Gabapentin was stopped as pain in his legs had resolved completely.   The authors stated that it was a rare presentation of neurological manifestations of reactivation of varicella zoster virus presenting as bilateral ptosis associated with a complete paralysis of bladder and bowel function in a fully vaccinated child (vaccination failure), and added that this case was a very important addition to the current body of literature on varicella-related neurological complications, as it outlined that varicella reactivation could present in completely vaccinated, immunocompetent young children as a neurological syndrome affecting the autonomic nervous system primarily and the rash can occur a few weeks later after presentation of the neurological symptoms. The presentation of this case was baffling due to the late appearance of a rash with initial presentation of isolated bilateral ptosis followed by gradual emergence of bladder and bowel retention indicating sacral parasympathetic involvement, but without motor involvement and without loss of deep tendon reflexes. causes. Bilateral acquired ptosis can be caused by neurogenic, myogenic, traumatic, aponeurotic and mechanical causes, and in this case, the differential included myogenic and neurogenic causes including myasthenia gravis, myotonic dystrophy, oculopharyngeal muscular dystrophy, GBS variant such as Miller Fisher syndrome, and rare neuro-metabolic disorders such as chronic progressive external ophthalmoplegia. In the patient, there was no involvement of the third nerve innervated extra ocular muscles, therefore the ptosis was related to weakness of the Muller muscles, which was confirmed by a detailed examination by a pediatric ophthalmologist. The appearance of rash almost 10 days after the neurological manifestations was another interesting feature in this case delaying the diagnosis, since rash and pain usually develop within a few days of each other, although pain can precede rash by weeks to months as in the case the patient (preherpetic neuralgia). The patient had received 2 doses of varicella virus vaccine live (oka/merck) (manufacturer unknown) at 1 and 5 years of age, but the authors could not find any records of the site of vaccination. Once the rash appeared, the clinical concern for a varicella zoster infection became stronger. Zoster IgM antibody was negative, however, the clinical features and the dermatomal distribution of the rash pointed towards this being consistent with a herpes zoster reactivation rash. Furthermore, the rapid response to acyclovir confirmed the diagnosis.  The outcome of varicella post vaccine and demyelinating polyneuropathy was considered as recovered/resolved with sequelae. The outcome of vaccination failure was not reported.  The authors considered varicella post vaccine, demyelinating polyneuropathy and vaccination failure to be related to varicella virus vaccine live (Oka/Merck) (manufacturer unknown), as they concluded that it was a unique case report of an immunocompetent vaccinated child presenting with serious neurological problems related to VZV vaccine reactivation.  Upon internal review, the event of demyelinating polyneuropathy was determined to be medically significant.  A copy of the published article is attached as further documentation of the patient's experience.