Diagnosis: Autoimmune Encephalopathy (Hashimoto’s)
Known case of hypothyroidism.
Placed on levothyroxin, displaying fairly controlled throid functions for last 4 years.
Grateful for relevant essential feedback/ suggestions/ alternative therapies/ experiences.
Patient capable and willing to reward recognized and certified medical intervention if found satisfactory.
Many thanks.
Diana.
Case History
Patient is 38 yrs female and has a background of likely thyrogastric autoimmunity, in that she has a history of hypothyroidism diagnosed ten years ago. This was picked up on routine testing for difficulty conceiving. The patient had a child 11 years ago, but then had a 6-year gap before that child and her next. She had no other symptoms of hypothyroidism. She was treated with levothyroxine and subsequently was able to have a second baby. A low vitamin B12 was noted in 2005 and then was noted to be normal in 2006. The patient also went gray and then white haired in her early 30s. Her father also has a history of this. Her father also has a history of type 1 diabetes. The patient’s main complaint began in 2005. Around February of that year, she began to develop symptoms of word finding difficulty, confusion, poor memory, and also some headaches. The patient has long standing history of migraine-type headaches without aura, nausea or vomiting but a severe unilateral headache that will often last for the day. These headaches were more diffuse and were associated with these cognitive symptoms as described above. She also noted that her balance was poor and that she had a a tendency to fall at times. She was seen by various doctors over a four month period without any improvement. Eventually, a diagnosis of a possible Hashimoto’s encephalopathy was made, and she was commenced on IVIG for five days. She said that she got back to normal very quickly with IVIG treatment and that this effect lasted for nine months. She subsequently had a relapse of her symptoms in November of 2005 and again received IVIG for five days. Again her symptoms resolved. On this occasion, she was only in remission for about five months, and her symptoms came back again. Again, she improved in March of 2006 with five days of IVIG back to baseline. In November 2006, she had a relapse of the symptoms again, but they were more severe on this occasion. She found that she was very very fatigued and also could not walk or talk straight. She also felt that her eye was swollen up, and she seem to be more disoriented and confused. She received IVIG for five days without any benefit, but then subsequently went into remission again with five days of IV m ethylprednisolone. Her thyroid autoantibodies were 90.5 when measured in February 2005 and fell over the period of 2006 up to the current time with various immunosuppression treatment as described above. She had a reading of 494 in 2005 also. She also had a reading of 60 in 2006, around November. Her most recent reading was 43.6. She has been on maintenance oral prednisolone since November 2006.. She said she tried going down to 5 mg of prednisolone a day but got a mild relapse of her symptoms which resolved on going back up to 10 mg of prednisolone per day. She also involved R focal seizures involving Right Upper Limb, lasting for few minutes and disappearing on its own. Tab Frisum (Clobazam) was advised which she took only for 4-6 months and stopped on her own.On further advice, Rheumatologist was consulted and he started the dose of Azathioprine 75 in the morning & 50 in the evening and oral Prednisolone on tapering dose. She has been on daily oral Prednisolone 10 mg and Azothioprine 125 mg. She started feeling weak and getting drained out from 3 rd week of March 2009. On 30t h March 09’, during her regular morning workouts, she fell and sustained a fracture of the lateral condyle of her left humerus. The exact basis of her fall is unclear. She does not remember the circumstance clearly. On 31 st March morning, she was operated under GA for her fracture, 2 metallic screws were fixed percutaneously. She withstood the procedure well but while coming out of the OT, she developed right focal seizures (involuntary movements) involving right upper limb, right trunk and right side of the face.
On 2 nd April, 8.30 am (IST) onwards she again developed continuous right focal seizures, lasting for more than 6.5 hours. Seizures continued despite of 2 gm I/V bolus of Levipil (Levetiracetam) along with repeat dose of I/V Lorazepam. During seizures plain CT Scan of brain was performed which revealed no major abnormalities. She was hospitalized on 2 nd April around 1:30 pm (IST) and multiple doses of I/V Midazolam & I/V Lorazepam was infused and Oral Clonazepam was given. Inspite of all the medication, the seizures continued and on 3 rd April she was airlifted to tertiary center and was on I/V Levipil (Levetiracetam) 500 mg 8 hourly, I/V Continous Midazolam 6 mg per hr , I/V Methylprednisolone 1 gm daily for 5 days (today being Day 5) and I/V Sodium Valproate 300 mg 8 hourly All base line investigations like CBC, ESR, Liver functions and Kidney functions are normal. Thyroid functions were normal except for TPO which is 65.3. EEG also shows no focal abnormality. All other body parameters are normal.
The phenomenology of the right sided focal involuntary movements involving the upper limb, shoulder, and occasionally, neck and face, were compatible with myoclonic dystonia; rather than focal seizures. There was no impairment in consciousness during these involuntary movements. However, she experienced fluctuating “confusion” and difficulty in finding words, her original cortical symptom. There were no pyramidal or cerebellar signs. The sensory examination was normal. She was administered clonazepam and acetazolamide following which the severity and frequency of her involuntary movements has reduced considerably. However, they do persist and are triggered by vocalization or voluntary movements. Brain MRI could not be done as she had recently implanted metallic screws in her left forearm. FDG PET of the brain has revealed global hypoperfusion of the brain with marked areas of focal hypoperfusion in the medial temporal and left parietal cortices. The basal ganglia perfusion appears normal. The impression of the team is that she has had an aggressive relapse of her SREAAT and appears to be refractory to steroids. Based on this, pulse IV Cyclophosphamide therapy was started, as the response to azathioprine as a steroid sparing agent appears clinically insignificant. On this recommendation, IV Cyclophosphamide 1.2 gm was given on 9th April and repeat 700mg on 27th April along with 1 gm Methylprednisolone daily; for 2 days, followed by 50 mg Prednisolone tablet daily. She is still bed-ridden, not able to stand on her own, has ataxia, suffers visual hallucination and intermittent (R) Myoclonic movements are still on.
SOCIAL HISTORY : The patient does not smoke. She does not drink alcohol. She runs a school, is an administrator which she has been setting up for the last few years, and has been very busy with this. During her episodes of illness, she has not been able to work. Subsequently, she had to give up work for a period.
FAMILY HISTORY : His father has type 1 diabetes. PHYSICAL EXAMINATION :
The physical examination otherwise was remarkable for mildly generalized brisk relexes. Her plantars were flexor. Sensory examination was normal. Coordination was normal. DIAGNOSIS:
Recurrent encephalopathic symptoms responsive to immunotherapy
Thyrogastric autoimmunity
Hypothyroidism
Pernicious anemia
INVESTIGATION :
1. BRAIN PET REPORT
Brain PET – CT Imaging (Date : 02-02-2009)
Findings :
Severe hypometabokism noted in bilateral medical temporal lobes (right > left)
Moderate hypometabolism in bilateral high parietal lobes and cerebellum.
Mild hypometabolism in bilateral frontal lobes.
Normal metabolism in lateral and anterior temporal lobes, occipital lobe, bilateral caudate nuclei and bilateral thalami
Comments :
· Abnormal Brain PET-CT scan.
· Scattered areas of hypometabolism more marked in bilateral high parietal lobes and bilateral medical temporal lobes.
· As compared to previous scan dated (18-02-2008) no change observed.
Brain PET – CT Imaging (Date : 07-04-2009)
Findings :
Global hypometabolism noted.
Severe hypometabolism noted in bilateral medial temporal lobes.
Moderate hypometabolism in left parietal lobe.
Normal metabolism in bilateral thalami and caudate nuclei.
Comments :
· Brain PET is abnormal.
· Global hypometabolism noted more marked in bilateral medial tempral lobes and left parietal lobe.
· As compared to brain PET dated 02-02-2009, there is increase in extent and severity of hypometabolism.
2. MRI
MRI did demonstrate a small area of T2 signal abnormality that looked a little cystic in appearance in the left insular cortex. This was unchanged throughout the three scans
3. EEG - No focal changes.
4. CSF - Normal
5. All biochemistry and general auto immune screen – investigation are well within normal limits.
Presently She is on :
Inj
Methylprednisolone 1000 mg
1gm daily for 2 days fortnightly
Inj
Cyclophosphamide 1000 mg
1 gm fortnightly
Tab
Prednisolone 50 mg
Daily
Tab
Resedronate 75 mg
Twice in a month
Cap
Alfacalcidol & Calcium 0.25 mcg & 250 mg
Once in a day
Tab
Clonazepam 0.5 mg
½ - ½ - 1
Tab
Sodium Valproate 200 mg
300 mg thrice in a day
Tab
Acetazolamide 250 mg
Twice in a day
Tab
Thyroxine 50 mcg
Once in a day
Cap
Omeprazole 20 mg
Once in a day
OUR CONCERN
Despite the high steroid dosages and two doses of Cyclophosphamide, the patient is immobile.
She is bed-ridden, visibly ataxic and suffers intolerable visual hallucination with intermittent myclonic movements.
Our primary concerns are two-fold:
Clearly understanding the multi-pronged approach needed to resolve present crisis; and,
Long term prognosis and line of treatment to avoid subsequent relapse.
