Hashimoto ’ s Encephalopathy : Case Report and Literature Review

Hashimoto’s encephalopathy is a rare disorder that causes relapsing-remitting or progressive confusion, impaired consciousness, seizures, ataxia, psychosis and myoclonus [1]. It is thought to be immune-mediated, though its exact pathophysiology remains speculative. It is also called non-vasculitic autoimmune meningoencephalitis, reflecting evidence of small vessel vasculitis [1-3]. We recently treated a patient with Hashimoto’s encephalopathy who responded well to glucocorticoid therapy and cyclophosphamide.


Introduction
Hashimoto's encephalopathy is a rare disorder that causes relapsing-remitting or progressive confusion, impaired consciousness, seizures, ataxia, psychosis and myoclonus [1].It is thought to be immune-mediated, though its exact pathophysiology remains speculative.It is also called non-vasculitic autoimmune meningoencephalitis, reflecting evidence of small vessel vasculitis [1][2][3].We recently treated a patient with Hashimoto's encephalopathy who responded well to glucocorticoid therapy and cyclophosphamide.

Case Presentation
A 43 year old right-handed man had a generalized tonic-clonic seizure necessitating intubation.Examination revealed spasticity, hyperreflexia, ankle clonus, and T= 38 C. Electrolytes, thyroid function tests, liver function tests, B12, folate, and ammonia were normal.CSF was negative for viral serologies including HSV, enterovirus, and arbovirus.Brain MRI with gadolinium was normal.A diagnosis of encephalitis was entertained.His cortisol level was low and he was discharged on a steroid taper.
He was re-admitted a few weeks later with increasing confusion, headaches and a generalized tonic-clonic seizure.EEG showed generalized slowing.CSF was normal including tests for HSV, EBV, Lyme, Cryptococcus, CMV, and VZV.He was treated with phenytoin, his sensorium cleared and he left against medical advice only to be re-admitted a week later after another seizure.Examination disclosed paranoid psychosis with delusions.Phenytoin was discontinued and Carbamazepine begun.EEG remained diffusely slow.Serum and urine protein electrophoresis, paraneoplastic panel, CT of the chest, abdomen and pelvis, and testicular ultrasound were normal.Brain MRI demonstrated diffusely increased cortical signal in FLAIR sequences bilaterally (Figure 1).Brain MRA was normal.CSF showed a lymphocytic pleocytosis and elevated protein.
Serologies for T. gondii, syphilis (serum and CSF) were negative.c-ANCA, p-ANCA, MPO, PR3, HIV, urine porphyrins and a heavy metal screen were negative.Thyroid function tests, including thyroid stimulating immunoglobulins, were normal.CSF JC virus PCR was positive and negative on repeat.Pancerebral angiography showed normal appearing cerebral vessels.
He improved after treatment with high dose glucocorticoid therapy and IV-Ig.Thyroid peroxidase antibodies were elevated at 410 IU/mL (normal <34 IU/mL).Thyroid-stimulating antibodies were <1 (normal <1.3) in the setting of a normal quantitative immunoglobulin screen.Thyroid ultrasound showed heterogeneous echogenicity in both lobes.He was treated with high-dose intravenous glucocorticoid therapy followed by a slow taper.Thereafter, he became more alert, conversant and demonstrated marked lessening of myoclonus and ataxia.Brain
Antithyroid antibodies -anti-thyroid peroxidase antibody (TPOAb) and or antithyroglobulin antibody (TgAb) -are the hallmark of this disease.There is no clear relationship between the severity of neurologic illness and serum concentration of antibody titers.Interestingly, the serum concentration does not correlate with treatment.Sensitivity ranges from 73-100% for these antithyroid antibodies [1].Serum auto-antibodies against the anti NH2-terminal of alpha enolase (NAE) have been implicated as a diagnostic marker for Hashimoto's encephalopathy with sensitivity of 90% and specificity of 50%.However, this particular auto-antibody needs to be evaluated further prior in order to elucidate its diagnostic as well as prognostic potential [6].
CSF protein elevation is seen in 75% and lymphocytic pleocytosis is present in 10-25% [1].Our patient demonstrated elevated protein, peaking at 70mg/dL, and lymphocytic pleocytosis.CSF oligoclonal bands have been reported [1] but were absent in our patient.Information regarding sequential CSF analysis in the literature is lacking.
Electroencephalographic abnormalities, when present, are usually nonspecific.Background slowing is observed in 94% of patients.Sharp waves and transient epileptic activity are less commonly seen [1,2,4].Our patient demonstrated background slowing on several EEGs.
Neuroimaging usually is normal.However, nonspecific T2 sequence abnormalities in the subcortical white matter and focal white matter changes suggestive of demyelination have been described [1,7].Follow-up imaging is often not obtained, but in some cases the MRI findings regress or resolve [1].Our patient demonstrated increased signal on the FLAIR sequence that regressed following glucocorticoid therapy.
Glucocorticoids are the mainstay of therapy in individuals afflicted with Hashimoto's encephalopathy.Systematic investigation into other immunosuppressants in the treatment of this disease is lacking.However, there are reports of anecdotal success with Azathioprine, Methotrexate and Mycophenolate mofetil, and intravenous immunoglobulin either alone, or in combination with Glucocorticoids [1,8].Cyclophosphamide was chosen in our patient for is its effective CNS penetration.
Clinicians should consider Hashimoto's encephalopathy in young patients with unexplained encephalopathy or rapidly progressing dementia.Elevated serum levels of anti-TPOAb and TgAb's coupled with a marked response to corticosteroids is diagnostic.Hashimoto's encephalopathy should be considered in the differential diagnosis of encephalopathies of unknown cause or rapidly-progressing neurodegenerative disorders because it is treatable and often has a favorable prognosis.

Figure 1 :
Figure 1: MRI Brain.FLAIR Sequence demonstrating increased signal over several cerebral sulci overlying the convexity.