Hashimoto’s encephalopathy: documentation of mesial temporal seizure origin by ictal EEG

Hashimoto's encephalopathy: documentation of mesial temporal seizure origin by ictal EEGCASE REPORT
Hashimoto’ s encephalopathy: documentation of mesial temporal seizure origin by ictal EEG
AMIR ARAIN, BASSEL ABOU-KHALIL & HAROLD MOSES
Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA
Correspondence to: Bassel Abou-Khalil, MD, Department of Neurology, Vanderbilt University, 2100 Pierce Ave., Rm. #336, Nashville, TN 37212, USA. E-mail: [email protected]
Hashimoto’s encephalopathy is a chronic relapsing and remitting encephalopathy associated with antithyroid antibodies. Seizures are a frequent manifestation, but are not well characterized in the literature with respect to their onset. We describe a 48-year- old patient with recurrent encephalopathy and seizures, and elevated antithyroid antibodies. One seizure was documented with video-EEG monitoring using scalp and sphenoidal electrodes. The ictal discharge originated in the left mesial-basal temporal region. MRI showed an increased T2 signal in the white matter of the centrum semiovale, but no temporal pathology. Symptoms resolved after treatment with prednisone and azathioprine. Hashimoto’s encephalopathy should be considered in patients with unexplained encephalopathy and seizures, including those originating in the temporal lobe.
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Key words:Hashimoto’s encephalopathy; seizures; temporal lobe; seizure onset; autoimmune disease.
INTRODUCTION
Hashimoto’s encephalopathy is an autoimmune, chronic relapsing condition, characterized by au- toantibodies against thyroid components1. It is an under-diagnosed steroid responsive encephalopathy1. Hashimoto’s encephalopathy is usually seen in associ- ation with other autoimmune disorders like rheuma- toid arthritis and systemic lupus erythematosis2, 3. Commonmanifestations include confusion, pyramidal tract signs, cerebellar signs, seizures, myoclonus, de- mentia and coma. Patients often present with seizures, both partial and generalized tonic–clonic. The inter- ictal EEG usually shows diffuse abnormalities includ- ing triphasic waves, frontal intermittent rhythmic delta activity (FIRDA), and generalized slowing4. The pub- lished literature includes only rare documentation of ictal recordings. We report a patient with Hashimoto’s encephalopathy who presented with recurrent confu- sion and secondarily generalized seizures documented to have a mesial temporal onset by ictal EEG.
CASE REPORT
History
A 48-year-old right-handed white female with a his- tory of rheumatoid arthritis was transferred from an- other hospital for evaluation of recurrent seizures in September of 1999. She had no previous his- tory of epilepsy. She initially presented to her lo- cal hospital in June of 1999 with nervousness, jit- teriness, mild confusion and worsening of postural tremor. She then had her first generalized tonic– clonic seizure. Head turning to the right was de- scribed early in the seizure. There was post-ictal con- fusion for several hours. She was started on pheny- toin. Her neurological symptoms improved over the next 2 days and she was discharged home after she returned to her baseline.
In July 1999 she had another bout of nervous- ness, jitteriness, and confusion which culminated in a
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seizure. She was readmitted. Her phenytoin level was low. She improved over the next few days and was discharged home on a higher phenytoin dose. She re- turned to baseline after discharge.
In August, she had another recurrence of nervous- ness, jitteriness and confusion. She was readmitted to her local hospital, then transferred to the Vanderbilt University Epilepsy Unit to determine if the mental status changes represented partial seizures. At the time of admission she was on phenytoin and gabapentin.
Physical examination
At presentation she was disoriented to time and place. She had inappropriate jocularity. Her spontaneous speech, naming, and auditory comprehension for two- step commands were normal. She made paraphasic er- rors on reading. She had poor attention with shortened digit span. She also had poor short-term memory (0/3 at 5 minutes). She could not perform any calculations. Cranial nerves were intact. Tone and power were nor- mal and symmetric. She had a postural tremor in both hands. She had a broad-based gait and was unable to perform tandem gait. Her reflexes were brisk and sym- metric. She had no pathologic reflexes. Sensory exam- ination was normal.
Laboratory testing
Evaluation included normal CBC, electrolytes, sedi- mentation rate, and ACE level, negative Lupus antico- agulant profile, negative RPR, negative Sjogren anti- bodies, negative ENA autoantibodies, negative ANA, negative anti-DNA antibodies and a negative ANCA.
Lumbar puncture showed a CSF pressure of 17 cm, a WBC count of 12µ l−1, an RBC count of 2µ l−1, a protein of 73 mg dl−1, and a glucose of 63 mg dl−1. CSF VDRL and cryptococcal antigen were non- reactive.
Thyroid function tests showed an elevated TSH con- centration of 18.8 (normal 0.30–5.0 mcU ml−1), free T4 of 0.4 (normal 0.6–1.8 ng dl−1), antithyroid G an- tibodies>57.0 (normal 0.0–2.0 U ml−1), antithyroid P antibodies>68.0 (normal 0.0–2.0 U ml−1).
MRI
A subtle increased T2 signal in the centrum semiovale was shown on MRI (Fig. 1). No hippocampal lesion was seen.
Fig. 1: A T2-weighted axial MRI showing an increased T2 signal in the white matter of the centrum semiovale, with posterior predominance.
Video-EEG monitoring
The patient was monitored with EEG and video us- ing scalp and sphenoidal electrodes. With phenytoin withdrawal she has one secondarily generalized tonic– clonic seizure. The seizure started with mumbling, looking around, and then fumbling with bed sheets. She had a couple of shudders, then had adversive head turning to the right and secondary generalization to a tonic–clonic seizure. The complex partial phase lasted 2 minutes and 25 seconds and the total seizure dura- tion was 3 minutes and 20 seconds.
Post-ictal exam suggested a right-sided Todd’s paralysis. She was alert but had a right gaze palsy. She also appeared to have a right-sided neglect. She had a right hemianopia and a right central facial weakness. She did not move her right side spontaneously, but moved her left. She did not cooperate for formal mus- cle testing. Reflexes were brisk but plantar responses were flexor bilaterally. Although she did withdraw to pain in all extremities, her threshold was much higher on the right side.
On EEG there was an insidious onset of a 6 Hz rhythmic discharge at the left sphenoidal electrode (Fig. 2). The ictal discharge spread to the left lateral temporalregion but remained predominant at the left sphenoidal electrode. The ictal discharge then gener-
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Fig. 2: Ictal EEG recording demonstrating a focal ictal onset in the left sphenoidal derivations.
alized. There was post-ictal slow wave activity and at- tenuationof faster frequencies in the left hemisphere. Before the seizure, the interictal EEG showed inter- mittent irregular slow wave activity in the right fronto- temporal region and, to a lesser extent, independently from the left temporal region. Occasional interictal epileptiform discharges were seen in the left fronto- polar region.
Treatment and outcome
The patient was started on prednisone 45 mg daily. As her mental status improved over the next few days she was discharged home on phenytoin 360 mg daily and prednisone 45 mg daily. She was instructed to taper prednisone by 5 mg every week till reaching 20 mg per day, then reduce her dose every other day to reach alternate day therapy. She was also treated with thy- roid replacement therapy.
She was seen in follow-up in the neuroimmunology clinic 1.5 months after discharge. She was seizure-free and had returned to her pre-morbid baseline mental status. She had just reduced her prednisone dose to 20 mg every other day. She was euthyroid. Her exam was non-focal and higher intellectual functions were intact.
She remained seizure-free with no recurrence of mental status changes 15 months after discharge. At her 4 month follow-up visit she was started on aza- thioprine to allow a reduction of prednisone. At her last telephone follow-up she was on prednisone 5 mg every other day and azathioprine 50 mg b.i.d.
DISCUSSION
Hashimoto’s encephalopathy, first described by Lord Brain5, is a steroid responsive relapsing encephalopa-
thy associated with antithyroid antibodies. The patho- genesis of the encephalopathy is unknown, but it is speculated that it may be related to immune complex deposition or the existence of a common antigen be- tween the brain and the thyroid gland1. The initial clin- ical manifestations are quite variable6–8. Therefore, a high index of suspicion is necessary for diagnosis. Initial symptoms range from mild confusion, irritabil- ity, focal manifestations such as hemiparesis, recurrent stroke-like events, ataxia, myoclonus, to complex par- tial or generalized tonic–clonic seizures1. The age at presentationvaries from 8 to 78 years6.
The interictal EEG findings are also variable. Most commonly the EEG shows generalized abnormalities including generalized slow wave activity, slow pos- terior background, bifrontal rhythmic delta waves4. Triphasic waves have also been reported4. Focal slow waves, as seen in our patient, were reported in five patients4, 9. The EEG findings seem to subside with the improvement of the encephalopathy6, though the EEGtends to lag behind the clinical improvement4.
There is only one published report of an ictal recording in Hashimoto’s encephalopathy. Vasconcel- loset al.9 reported a 16-year-old girl with Hashimoto’s encephalopathywho had independent bitemporal ic- tal discharges with a wide temporal field. Our patient is the first we found with a documented focal mesial- basal temporal seizure onset. The ictal seizure semiol- ogy, with the gradual onset and slow secondary gen- eralization, was also consistent with a temporal onset. However, interictal epileptiform discharges were not recorded from the mesial temporal region.
There was no structural abnormality in the mesial temporal structures on MRI. This does not exclude pathology in the medial temporal structures, such as immune-mediated injury. An immune-mediated origin is most likely for this patient’s condition, in view of the presence of another autoimmune condition (rheuma- toid arthritis), and in view of the disappearance of
Hashimoto’s encephalopathy 441
symptoms, including seizures, with steroids and aza- thioprine.Another presumed autoimmune condition, limbic encephalitis, presents with manifestations re- lated to mesial temporal dysfunction10. In limbic en- cephalitis mesial temporal structures may have in- creased signal or may be normal11, 12. There is often overlap in the manifestations of different autoimmune disorders, and several autoimmune conditions may co- exist in the same patient3. Besides the site of seizure origin, our patient had evidence of limbic dysfunc- tion from her memory loss. An amnestic syndrome with bilateral MRI mesial involvement was reported in Hashimoto’s encephalopathy13. In Hashimoto’s en- cephalopathythe reported MRI findings are variable. They range from normal findings to a focal mesial temporal increased T2 signal, to a diffuse increased T2 signal in the cerebral white matter13, 14.
Our patient emphasizes that Hashimoto’s en- cephalopathy is a treatable condition. The clinical pic- ture can be quite variable, but the presence of unex- plained encephalopathy and seizures should suggest the possibility of this diagnosis, and prompt screen- ing for antithyroglobulin antibodies. Treatment with steroids and immunosuppressants is effective in treat- ing the encephalopathy as well as bringing previously refractory seizures under control.
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Introduction