Second edition

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and it was this association of Hashimoto’s thyroiditis
with delirium that prompted the new term, ‘Hashimoto’s
encephalopathy’. Importantly, however, as noted below,
although anti-thyroid antibodies are present in all cases
of Hashimoto’s encephalopathy, there is no association
between the encephalopathy and thyroid disease, and it
appears that the anti-thyroid antibodies are merely ‘innocent
bystanders’ that serve as markers of a more widespread
autoimmune disorder; in addition to autoantibodies
directed at the thryoid, other autoantibodies directed at the
brain are also present.
A recently coined synonym for Hashimoto’s encephalopathy
is ‘steroid-responsive encephalopathy associated with
autoimmune thyroiditis’ or ‘SREAT’. Whether this new
terminology is helpful or will gain currency remains to
be seen.
Clinical features
The clinical features have been most clearly described in
two case series from the Mayo Clinic (Castillo et al. 2006;
Sawka et al. 2002). Although most patients are in their forties,
the age of onset varies widely, from childhood to the
eighth decade; the onset itself is typically subacute, over
days or perhaps weeks.
The overwhelming majority of patients have a delirium,
which in most cases is accompanied by any or all of tremor,
myoclonus, ataxia, or seizures; seizures may be grand mal,
complex partial or, rarely, simple partial, and grand mal
status epilepticus may occur in a small minority. Strokelike
episodes are common and are typically characterized
by aphasia (Bohnen et al. 1997; Ghika-Schmid et al. 1996;
Henchey et al. 1995; Shaw et al. 1991; Thrush and Boddie
1974); hemiplegia or hemisensory loss may also occur.
These stroke-like episodes are of brief duration, lasting in
the order of hours or a day or more, and typically undergo
a full remission. Very rarely Hashimoto’s encephalopathy
may present with a psychosis (Bostantjopoulou et al. 1996)
or with a dementia (Galluzzi et al. 2002).
Magnetic resonance scanning is normal in the majority of
cases; in the remainder, T2-weighted or FLAIR imaging may
disclose diffusely increased signal intensity in the cerebral
white matter (Bohnen et al. 1997) and, in a small minority,
subcortical infarctions may be noted. (Henchey et al. 1995).
Computed tomography scanning is almost always normal.
The EEG shows generalized slowing in the vast majority
of cases, and this may be accompanied by other changes in
a small minority, including triphasic waves and interictal
epileptiform discharges (Schauble et al. 2003).
The CSF typically, but not always, displays various
abnormalities. An elevated total protein is most common;
in a small minority there may be a mild lymphocytic pleocytosis.
Rarely, there may be oligoclonal bands or the 14-3-3
protein (Hernandez Echebarria et al. 2000).
A small minority may have a mildly elevated ANA or
ESR. Thyroid indices are generally normal; if abnormal
17.9 Hashimoto’s encephalopathy 557
one typically sees only a mildly reduced thyroxine (T4) and
a mildly elevated thyroid-stimulating hormone (TSH)
(Henchey et al. 1995; Shaw et al. 1991).
Elevations of anti-thyroid antibodies, either anti-thyroid
peroxidase or anti-thyroglobulin, are present in all cases.
Although in the vast majority of cases both of these are elevated,
exceptions do occur and patients may have elevation
of only one; consequently, both should be routinely tested
for. Typically the levels of these antibodies are elevated tenfold
or greater; importantly, however, there is no correlation
between the degree of elevation and the severity of the
clinical syndrome
Course
Although the course of Hashimoto’s encephalopathy has
not been clearly delineated, it appears to be an episodic disease.
The episodes themselves tend to persist for anywhere
from weeks up to 6 months, after which there is generally a
remission. Repeat episodes can occur; however, it is not
clear whether this is the case for all, or even most, patients,
nor is it clear how long the intervals are between episodes.
Etiology
Neuropathologically there is widespread perivascular lymphocytic
inflammation, microglial activation, and gliosis
(Castillo et al. 2006; Chong et al. 2003; Doherty et al. 2002;
Duffey et al. 2003; Nolte et al. 2000).
Although the mechanism underlying this inflammatory
change has not been positively identified, an autoimmune
process is strongly suggested both by the association with
anti-thyroid antibodies and by the good response to
steroids. In all likelihood, however, the anti-thyroid antibodies
are not pathogenic but merely represent part of a
wider autoimmune response, with other antibodies directed
at the brain; in this regard serum anti-neuronal antibodies
have been demonstrated (Oide et al. 2004) and one study
identified a particular autoantibody directed at alpha-enolase
(Ochi et al. 2002).
Differential diagnosis
Various other causes of delirium, as discussed in Section
5.3, must be considered, including toxic deliria (serotonin
syndrome, neuroleptic malignant syndrome, delirium
tremens), metabolic deliria (Wernicke’s encephalopathy,
uremic encephalopathy, hepatic encephalopathy), other
autoimmune disorders (systemic lupus erythematosus,
limbic encephalitis), intracranial disorders (hypertensive
encephalopathy, posterior reversible leukoencephalopathy
syndrome), viral encephalitis, complex partial status epilepticus,
and Creutzfeldt–Jakob disease (which may closely
mimic Hashimoto’s encephalopathy [Doherty et al. 2002]).