I should note, from our research we’re also seeing cases of cerebellar ataxia post fluoroquinolone reaction and related to Hashimoto’s thyroiditis. The cerebellum appears to be particularly sensitive to insult from environmental toxins – to functional mitochondrial injuries, perhaps because it collects the millions of peripheral nerves coming from the body that control sensation and movement, as they pass to higher brain centers. As such, the cerebellum demands high levels of oxygen and nutrients.
For those of our readers new to neuroanatomy, the cerebellum is the cauliflower looking section at the base of the brain that controls motor coordination – the ability to perform coordinated tasks such as walking, focusing on a visual stimuli and reaching for objects in space. The walking and balance disturbances associated with cerebellar damage or degeneration have a very distinct look, a wide gait, with an inability to walk heal to toe – very much like a drunken sailor. Videos of cerebellar ataxia can be seen here.
The Case Details: Acute Cerebellar Ataxia Post HPV Vaccine
Approximately, two weeks after receiving the HPV vacccine, Cervarix, a previously healthy 12.5 year old girl developed nausea and dizziness with severe cerebellar ataxia, tremors and nystagmus. Initial tests came back normal and she was hospitalized on day 20 post HPV vaccine. Though she could sit on her own, she could not stand or walk unaided and the nystagmus prevented her from focusing on TV, reading or other activities. She had no fever. Heel-knee-shin and finger-nose tests indicated ataxia with terminal intention tremor and dysmetria (see videos: horizontal nystagmus or here for multiple types of nystagmus, heel-knee-shin test, finger-nose test).
All blood tests, cerebral spinal fluid tests and imaging tests were normal, with the exception of testing positive for IgG and varicella zoster virus – chicken pox and shingles – indicating earlier exposure. Tumors, paraneoplastic disease, cardiovascular disease, metabolic conditions and labyrinthitis (inner ear disturbance) were all ruled out. Her symptoms did not remit as was expected with acute cerebellar ataxia.
Treatment Options for Acute Cerebellar Ataxia
Beginning on day 25 post HPV vaccine, pulsed IV methylprednisone (1000mg/d) was administered for three days. Her symptoms persisted. On day 44 post HPV vaccine, IV immunoglobulin (IVIG) at 400mg/kg was initiated and run for 5 days. Her symptoms persisted.
At day 65 post vaccine, with no indication of improvement, immunoadsorption plasmapharesis was begun at a rate of seven times per month. The physicians report a gradual improvement of the nystagmus after two treatments with a full resolution of symptoms after 19 courses of treatment (day 134 post HPV vaccine). The improvement was short-lived, however, and beginning at day 220 post HPV vaccine, the symptoms began to return, gradually at first with nystagmus, and then completely. Immunoadsorption plasmapharesis was begun anew on day 332 post HPV vaccine. After five courses of treatment, the patient’s symptoms again remitted.
Immunoglobulin G (IgG) and Cerebellar Ataxia Symptoms
Of interest, symptom severity corresponded to IgG levels. Her initial IgG levels were not reported, but after 19 treatments, when symptoms disappeared completely for the first time, her IgG levels were 354 mg/dL (day 134). When the symptoms appeared again (day 332) her IgG levels were elevated at 899 mg/dL. Upon treatment, her IgG levels dropped to 503 mg/dL as the nystagmus abated and then to 354 mg/dL upon complete remission, for the second time, at day 332 post HPV vaccine.
HPV16L and Post HPV Vaccine Reactions and Death
The researchers from this study, speculate a connection between the IgG response, and an as of yet, undetermined antibody. Testing for a variety of known antibodies were negative. Since the HPV16L is molecularly similar to certain cell adhesion molecules, enzymes, transcription factors and neural antigens, it is possible that the HPV16L particles triggered the response.
In separate studies, autopsies of girls who died suddenly post HPV vaccine have found non-degrading HPV16L particles linked to the deaths. In the first case, researchers performed secondary postmortem immunochemistry of two girls who died suddenly after receiving Gardasil. They found evidence of cerebral vasculitis linked to the HPV16L particles throughout the cerebral vasculature.
Similarly, a postmortem exam of another girl who died from the HPV vaccine, found HPV16L DNA particles in the blood and spleen. The researcher reported that the DNA fragments were found in the macrophages, and protected from degradation because of the tight binding of the HPV16L gene fragments to the aluminum adjuvant. The fragments underwent a conformational change rendering them more ‘stable’ and resistant to degredation, perhaps explaining their presence in the blood and spleen six months post vaccine. This has been contended.
Methods in both of the above studies have been controversial and questioned and should be interpreted with caution. However, researchers from Italy compared HPV16 proteome in the vaccine to the human to proteome and found 84 identical proteins involved in cell differentiation and neurosensory regulation. According to these researchers, the homology between the vaccine and the human proteome, bound to aluminum adjuvant
“make the occurrence of side autoimmune cross-reactions in the human host following HPV16-based vaccination almost unavoidable”.
Whatever the exact culprit, in this case the cerebellar ataxia was acute and temporally related to the HPV vaccine. The favorable response to immunoadsorption and consequent reduction in IgG levels, indicates an auto-immune response.
Mitochondrial Injury, Thyroid, Thiamine and Cerebellar Ataxia
With a more slowly developing cerebellar ataxia and related symptoms, it is possible a medication induced mitochondrial injury, related to a depletion of thiamine is present. Thiamine is critical for mitochondrial function. Similarly, patients have reported cerebellar ataxias related to Hashimoto’s. Generally, when testing for both thiamine deficiency and Hashimoto’s is undertaken, both are confirmed.
This report represents one of the first clear linkages between the HPV vaccine and acute cerebellar ataxia. More importantly, it suggests a treatment opportunity when caught early. With so little data available, it is not clear whether immunoadsorption would work for more chronic cases. However, there is evidence of its success in Guillian Barre, Myasthenia Gravis and other autoimmune conditions. When combined with the early data pointing to Hashimoto’s and thiamine deficiency, paths forward post injury are emerging.
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