Human disease (neurological condition)
Medical condition
Hashimoto's encephalopathy
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Other names
| Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT)
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Brain
SPECT
transaxial images of a patient afflicted with Hashimoto's encephalopathy.
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Specialty
| Neurology
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Hashimoto's encephalopathy
, also known as
steroid-responsive encephalopathy associated with autoimmune thyroiditis
(
SREAT
), is a neurological condition characterized by
encephalopathy
, thyroid autoimmunity, and good clinical response to
corticosteroids
. It is associated with
Hashimoto's thyroiditis
, and was first described in 1966. It is sometimes referred to as a
neuroendocrine
disorder, although the condition's relationship to the endocrine system is widely disputed. It is recognized as a rare disease by the NIH Genetic and Rare Diseases Information Center.
[1]
Up to 2005, almost 200 case reports of this disease were published. Between 1990 and 2000, 43 cases were published. Since that time, research has expanded and numerous cases are being reported by scientists around the world, suggesting that this rare condition is likely to have been significantly undiagnosed in the past. Over 100 scientific articles on Hashimoto's encephalopathy were published between 2000 and 2013.
[2]
Signs and symptoms
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]
The onset of symptoms tends to be fairly gradual and to occur over 1-12 years.
[
citation needed
]
Symptoms of Hashimoto's encephalopathy may include:
[
citation needed
]
- Personality changes
- Aggression
- Delusional behavior
- Concentration and memory problems
- Coma
- Disorientation
- Headaches
- Jerks in the muscles (
myoclonus
? 65% of cases)
- Lack of coordination (
ataxia
? 65% of cases)
- Partial
paralysis
on the right side
- Psychosis
- Seizures
(60% of cases)
- Sleep abnormalities (55% of cases)
- Speech problems (transient
aphasia
? 80% of cases)
- Status epilepticus
(20% of cases)
- Tremors (80% of cases)
Pathogenesis
[
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The mechanism of pathogenesis is not known, but is thought to be an autoimmune disorder, similar to
Hashimoto's thyroiditis
, as its name suggests.
[
citation needed
]
Consistent with this hypothesis,
autoantibodies
to
alpha-enolase
have been found to be associated with Hashimoto's encephalopathy.
[3]
Since
enolase
is the penultimate step in glycolysis, if it were inhibited (for example by being bound by autoantibodies), one would expect decreased energy production by each cell, leading to resulting
atrophy
of the affected organ.
[
citation needed
]
This would occur most likely through each cell shrinking in size in response to the energy deficit (and/or in extreme situations from some cells dying via either apoptosis or necrosis, depending on location).
[4]
This may occur as a result of enough ATP not being available to maintain cellular functions - notably, failure of the Na/K ATPase, resulting in a loss of the gradient to drive the Na/Ca antiporter, which normally keeps
Ca
+
2
out of cells so it does not build to toxic levels that will rupture cell lysosomes leading to apoptosis. An additional feature of a low-energy state is failure to maintain axonal transport via dynein/kinesin ATPases, which in many diseases results in neuronal injury to both the brain and/or periphery.
[5]
Pathology
[
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Very little is known about the pathology of Hashimoto's encephalopathy.
Post mortem
studies of some individuals have shown lymphocytic vasculitis of venules and veins in the brain stem and a diffuse gliosis involving gray matter more than white matter.
[
citation needed
]
As mentioned above, autoantibodies to alpha-enolase associated with Hashimoto's encephalopathy have thus far been the most hypothesized mechanism of injury.
[3]
Diagnosis
[
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]
Laboratory and radiological findings
[
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]
- Increased
liver
enzyme levels (55% cases)
- Increased thyroid-stimulating hormone (55% cases)
- Increased erythrocyte sedimentation rate (25% cases)
Cerebrospinal fluid
findings:
[
citation needed
]
Thyroid hormone abnormalities are common (>80% of cases):
[
citation needed
]
- Subclinical hypothyroidism (35% of cases)
- Overt hypothyroidism (20% of cases)
- Hyperthyroidism (5% of cases)
- Euthyroid on levothyroxine (10% of cases)
- Euthyroid not on levothyroxine (20% of cases)
Thyroid antibodies ? both antithyroid
peroxidase
antibodies (anti-TPO, antithyroid microsomal antibodies, anti-M) and anti
thyroglobulin
antibodies (anti-Tg) ? in the disease are elevated, but their levels do not correlate with the severity.
[
citation needed
]
Electroencephalogram
studies, while almost always abnormal (98% of cases), are usually not diagnostic. The most common findings are diffuse or generalized slowing or frontal intermittent rhythmic delta activity. Prominent triphasic waves, focal slowing, epileptiform abnormalities, and photoparoxysmal and photomyogenic responses may be seen.
[6]
A study from 2006 suggested the following diagnostic criteria:
[7]
- Encephalopathy with cognitive impairment and at least one of the following features:
- neuropsychiatric symptoms (e.g. hallucination, delusion or paranoia)
- Myoclonus, generalised tonic-clonic or partial seizures
- focal-neurological deficits
- Elevated titres of thyroid tissue antibodies (TPO-ab or microsomal)
- Euthyroidism (potentially achieved by treatment with L-T4 or L-T3) or mild hypothyroidism with TSH concentration below 20 mIU/L
- No evidence for infectious, toxic, metabolic or neoplastic processes in blood, urine or CSF analyses
- No serological evidence for neuronal antibodies (e.g. voltage-gated calcium channel, voltage-gated potassium channel, or other currently recognized paraneoplastic antibodies) to support another diagnosis
- In imaging studies no evidence for vascular, neoplastic or structural lesions that might explain the symptoms
- Complete or nearly complete remission after initiation of glucocorticoid therapy.
Definition
[
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]
A relapsing encephalopathy occurs in association with autoimmune (Hashimoto's or Ord's thyroiditis), with high titers of antithyroid antibodies. Clinically, the condition may present one or more symptoms. Onset is often gradual and may go unnoticed by the patient and close associates to the patients. Symptoms sometimes resolve themselves within days to weeks, leaving a patient undiagnosed. For many other patients, the condition may result in ongoing problems with a variety of manifestations, often confusing clinicians due to the diffuse nature of symptoms.
[
citation needed
]
Differential diagnosis
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Treatment
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]
Because most patients respond to
corticosteroids
or
immunosuppressant
treatment, this condition is now also referred to as steroid-responsive encephalopathy.
[
citation needed
]
Initial treatment is usually with oral
prednisone
(50?150 mg/day) or high-dose intravenous
methylprednisolone
(1 g/day) for 3?7 days. Thyroid hormone treatment is also included if required. Failure of some patients to respond to this first-line treatment has produced a variety of alternative treatments, including
azathioprine
,
cyclophosphamide
,
chloroquine
,
methotrexate
, periodic intravenous immunoglobulin, and plasma exchange. No controlled trials have been conducted, so the optimal treatment is not known.
[
citation needed
]
Seizures, if present, are controlled with typical antiepileptic agents.
[
citation needed
]
Prognosis
[
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Duration of treatment is usually between 2 and 25 years. Earlier reports suggested that 90% of cases stay in remission after discontinuation of treatment, but this is at odds with more recent studies, which suggest that relapse commonly occurs after initial high-dose steroid treatment.
[7]
[8]
Left untreated, this condition can result in coma and death.
[
citation needed
]
Epidemiology
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The prevalence has been estimated to be 2.1/100,000
[9]
with a male-to-female ratio of 1:4. The mean age of onset is 44 with 20% of cases presenting before the age of 18 years. Most reported cases occur during the patient's fifth decade of life.
[
citation needed
]
History
[
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]
The first case of HE was described by
Brain
et al. in 1966.
[10]
The patient was a 48-year-old man with
hypothyroidism
, multiple episodes of
encephalopathy
,
stroke-like symptoms
, and Hashimoto's thyroiditis confirmed by elevated antithyroid antibodies.
Alternative names
[
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]
- Steroid-responsive encephalopathy associated with autoimmune thyroiditis, SREAT
- Nonvasculitic autoimmune meningoencephalitis, NAIM
- Encephalopathy associated with autoimmune thyroid disease, EAATD
References
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]
- ^
"Hashimoto's encephalitis - Disease - Overview"
. Genetic and Rare Diseases Information Center (GARD). Archived from
the original
on 2016-08-07
. Retrieved
2013-11-21
.
- ^
"Scientific Research/Articles ? Articles Published in 2014"
. hesaonline.org. Archived from
the original
on 2013-07-08.
- ^
a
b
Fujii A, Yoneda M, Ito T, Yamamura O, Satomi S, Higa H, Kimura A, Suzuki M, Yamashita M, Yuasa T, Suzuki H, Kuriyama M (May 2005). "Autoantibodies against the amino terminal of alpha-enolase are a useful diagnostic marker of Hashimoto's encephalopathy".
J. Neuroimmunol.
162
(1?2): 130?6.
doi
:
10.1016/j.jneuroim.2005.02.004
.
PMID
15833368
.
S2CID
43249019
.
- ^
Shigeomi Shimizu2, Yutaka Eguchi, Wataru Kamiike, Yuko Itoh, Jun-ichi Hasegawa, Kazuo Yamabe, Yoshinori Otsuki, Hikaru Matsuda, and Yoshihide Tsujimoto
The First Department of Surgery. Department of Medical Genetics. BiomedicalResearch Center. Osaka University Medical School, 2-2 Yatnadfioka, Sunti 56.5. Japan, and Depannient of Anatomy and Biology. Osaka Medical College. Japan.| url=
http://cancerres.aacrjournals.org/content/56/9/2161.full.pdf
- ^
Ihejirika DF. PASS Program Course Notes: USMLE Preparation. Lulu.com; 2014.
- ^
Li, Jie; Li, Fengzhen (2019-05-08).
"Hashimoto's Encephalopathy and Seizure Disorders"
.
Frontiers in Neurology
.
10
: 440.
doi
:
10.3389/fneur.2019.00440
.
ISSN
1664-2295
.
PMC
6517482
.
PMID
31133960
.
- ^
a
b
Castillo P, Woodruff B, Caselli R, et al. (February 2006).
"Steroid-responsive encephalopathy associated with autoimmune thyroiditis"
.
Archives of Neurology
.
63
(2): 197?202.
doi
:
10.1001/archneur.63.2.197
.
PMID
16476807
.
- ^
Flanagan EP, McKeon A, Lennon VA, et al. (October 2010).
"Autoimmune dementia: clinical course and predictors of immunotherapy response"
.
Mayo Clinic Proceedings
.
85
(10): 881?97.
doi
:
10.4065/mcp.2010.0326
.
PMC
2947960
.
PMID
20884824
.
- ^
Ferracci F, Bertiato G, Moretto G (February 2004). "Hashimoto's encephalopathy: epidemiologic data and pathogenetic considerations".
Journal of the Neurological Sciences
.
217
(2): 165?8.
doi
:
10.1016/j.jns.2003.09.007
.
PMID
14706219
.
S2CID
19827218
.
- ^
Brain L, Jellinek EH, Ball K (September 1966). "Hashimoto's disease and encephalopathy".
The Lancet
.
2
(7462): 512?4.
doi
:
10.1016/S0140-6736(66)92876-5
.
PMID
4161638
.
Further reading
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