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Selim and Drachman described six patients with a progressive sporadic adult onset cerebellar degeneration.1 Raised concentrations of antithyroid antibodies were found. Modest increases in antithyroid antibodies were considered to be the result of longstanding autoimmune thyroid disease. Analysis of CSF showed increased protein concentrations in one patient. Brain MRI disclosed atrophy of the vermis in four patients and showed a concomitant atrophy of the brain stem in two patients. Treatment with L-thyroxine did not improve cerebellar signs. The authors suggested that ataxia associated with Hashimoto's disease could be due to an autoimmune cerebellar degeneration.
This is a very interesting finding, which raises several issues for the diagnosis and management of sporadic adult onset cerebellar degeneration. I make three comments. Firstly, there is another clinical presentation of “Hashimoto's associated ataxia”,2 consisting of an acute cerebellar syndrome associated with abnormal behaviour. Protein concentrations are increased in CSF. Brain MRI shows a high intensity signal in T2 weighted images, restricted to the cerebellum. This other presentation should not be overlooked because steroids and thyroid hormonal therapy improve the cerebellar deficits markedly. This ataxic syndrome associated with Hashimoto's thyroiditis differs from the cases reported recently1 by (1) the acute onset, (2) distinct MRI findings, and (3) the dramatic clinical/radiological response to treatment which is a strong argument in favour of an immune attack against the cerebellum.
The authors should consider multiple system atrophy (MSA) in the differential diagnosis of sporadic adult onset cerebellar degeneration.3,4 Various combinations of extrapyramidal, pyramidal, cerebellar, and autonomic features occur in MSA. The disorder having an estimated prevalence ratio of 16.4/100 0005; raised concentrations of antithyroid antibodies might be a coincidence. Patient 6 exhibited cerebellar deficits associated with autonomic/urinary dysfunction, pyramidal signs (bilateral Babinski's signs), and parkinsonism (axial rigidity, hypertonia).1 Multiple system atrophy is likely in this patient. Were sphincter EMG studies performed? Were dysautonomic signs specifically looked for in other patients?
In one of our patients exhibiting a chronic and sporadic cerebellar syndrome with atrophy, high concentrations of antinuclear antibodies and presence of a rheumatoid factor were initially considered as markers of an immune disease producing a cerebellar degeneration. However, a subsequent genetic testing disclosed a spinocerebellar ataxia type 6 (SCA-6). Genetic analysis for SCA-1 to 7 was performed in one of the patients reported by Selim and Drachman,1 and was not available in the remaining five patients. Detailed genetic tests should be carried out, even when there is no family history of ataxia. Recent studies show that about 4% of patients with a sporadic ataxia harbour a mutation.6 Negative genetic results would reinforce the appealing concept of “Hashimoto's associated ataxia”.
The author is supported by the Belgian National Research Foundation.
We thank Dr Manto for bringing to our attention this reported case of acute Hashimoto's encephalopathy with confusion, focal cerebellar signs, and MRI changes. Although the clinical manifestations, tempo, and imaging findings of the disease were clearly different, it is entirely plausible that this patient shared immunity as its underlying mechanism with the six patients we reported. It underlines the breadth of manifestations that may occur in autoimmune disorders of the CNS.
Precisely which structures are targeted to produce these varying clinical manifestations is unclear. Whether thyroperoxidase antibodies target Purkinje cells, or whether the increase in antithyroid antibodies reflects a broader autoimmune diathesis, is unknown. The similarity of this gradually progressive cerebellar disorder to that reported with antiglutamic acid decarboxylase (GAD) antibodies is also of interest.1 The entire clinical range of progressive cerebellar impairment due to autoimmune disorders has yet to be elucidated; and multisystem atrophy may well overlap clinically, aetiologically, or both.
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