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Journal of Case Reports
Hashimoto’s Encephalopathy: Is it a Rare Condition or a Masquerading One?
Robin George Manappallil
Consultant-Physician, Department of Medicine, National Hospital, Calicut, Kerala 673001, India.
Corresponding Author:
Dr. Robin George
Email: drrobingeorgempl@gmail.com
Received: 27-AUG-2015 Accepted: 13-OCT-2015 Published Online: 15-NOV-2015
DOI: http://dx.doi.org/10.17659/01.2015.0126
Abstract
Hashimoto’s encephalopathy is an uncommon neurological disorder of unknown etiology, found in association with thyroid autoimmunity. This is a case of a 60 year old Indian lady who had an episode of acute onset encephalopathy. High levels of antithyroid antibodies were found in her serologic studies. Her cerebrospinal fluid analysis was near normal. Magnetic resonance imaging showed a lacunar infarct in pons and vasculitis. Her electroencephalographic studies were consistent with Hashimoto’s encephalopathy. Hashimoto’s encephalopathy is a poorly understood syndrome, which is often under recognized because of its heterogeneous neurological symptoms. Hence, it is important to have an insight regarding the clinical manifestations and treatment of this rather uncommon condition. 
Keywords : Brain Diseases, Electroencephalography, Hashimoto Disease, Magnetic Resonance Imaging, Lacunar Stroke.
Introduction

Hashimoto’s encephalopathy (HE) is a rare  neurological disorder. Due to the presence of high  titres of antithyroid antibodies, this condition is presumed to be associated with thyroid  autoimmunity. Brain vasculitis and autoimmunity directed against common brain-thyroid antigens have been  proposed as  the most likely etiological  pathway. These patients can present with unexplained seizures resistant to anticonvulsive therapy, confusion, headaches, hallucinations, stroke-like  episodes,  impaired  cognitive function, behavioural and mood disturbance, ataxia, and  presenile dementia. The thyroid functions may  be  normal or  decreased in these patients but serologic studies will reveal the presence of high antithyroid antibody levels, especially against thyroperoxidase. Cerebrospinal fluid (CSF) analysis,  magnetic resonance imaging (MRI) brain and electroencephalographic (EEG) studies can further aid in its diagnosis. These patients may have a subacute or acute onset, with dramatic recovery following corticosteroid therapy.

Case Report

The  patient  being  reported  in  this  case  is  a  60  year  old  unmarried  lady,  a  retired  government  officer.  She  was  diagnosed  to  have  schizophrenia  at  the  age  of  24,  but  was  on  irregular  treatment  and  follow  up.  Over  a  period  of  one  year,  her  relatives  have  noticed  a  mild  difficulty  in  walking  and  dressing,  poor  hygiene,  increased  irritability,  amnesia  and  disorientation.

    On  the  day  of  presentation,  she  was  found  unconscious  in  her  bed  with  uprolled  eyes  and  tongue  bite,  surrounded  by  vomitus.  She was brought  to  the  emergency  department in  unconscious state.  Her  vitals  showed  a  heart  rate  of  70  beats/ minute,  blood  pressure  of  160/100 mmHg,  respiratory  rate  of  22 breaths/minute  and  temperature  99oF.  Her oxygen saturation was 94% in room air.  On  neurological  examination,  her  Glasgow  Coma  Scale  (GCS)  score  was  E1V2M1.  Her pupils were bilaterally symmetrical and reacting to light.  Deep tendon reflexes were normal and plantars bilaterally flexor.  Mild tremors were present over her left upper limb.  There was no neck stiffness.  Respiratory  system  examination  revealed  minimal  right  sided  crepitations,  while  her  cardiovascular  and  abdominal  examinations  were  normal.  Her computed tomography (CT) brain did not show any  abnormalities.  Her  chest  X-ray  showed  mild  right  sided  aspiration  pneumonia  and  ECG  was  normal.  Her complete blood count showed elevated total counts with neutrophilia.  Her  sugar  levels,  renal  and  liver  functions  and  electrolytes  were  normal.  Her  thyroid  functions  revealed  TSH  of  4.10  IU/L,  FT3  2.43  pg/mL  and  FT4  1.1  ng/dL.  A  probable  diagnosis  of  cerebrovascular  accident  with  seizures  and  hypoxic  encephalopathy  and  aspiration  pneumonia  was  made,  and  the  patient  was  started  on  antiplatelet  drugs,  statins,  antiepileptic  drugs,  mannitol  and  intravenous  antibiotics. 

    On  day  2,  MRI  brain  was  taken  which  revealed  lacunar  infarct  in  left  pontine  region  and  vasculitis.  Her  CSF  analysis  showed  mildly  elevated  proteins  and  normal  counts  and  glucose  levels. On  day  3,  patient  became  conscious  and  her  GCS  showed   mild  improvement  to  E2V3M1.  Her viral markers i.e. HIV, HBsAg, anti HBs and anti HCV were negative.  Her  antinuclear  antibody  titre,  anti-double  stranded  DNA,    anti neutrophil  cytoplasmic  antibodies (p-ANCA and c-ANCA)  were  normal.  Over the next two days, her total counts became normal.  However, there was no further improvement in her neurological status.

    Her EEG showed a slow background with theca waves.  Based  on  the  history,  clinical  presentation  and  investigations,  the  possibility  of  HE  was  considered  and  antithyroid  peroxidase  antibody   was  sent,  which  was  well  elevated  (852  IU/mL). The patient was started on oral prednisolone 1 mg/kg/day.  On day 8, patient showed dramatic improvement.  She became conscious and started obeying simple commands.  Over  the  next  three  days,  she  was  able  to  walk  and  was  discharged  on  day  12  on  tapering  dose  schedule  of  prednisolone.

Discussion

HE is a rare neurological disorder of unknown aetiology.  This  term  was  coined  for  the  first  time  by  Shaw  in  1991.  He  had  come  across  5  cases  with  symptoms  such  as  seizures, frequent episodes  of  alternating  hemiparesis  and  disorientation.  They also had   high protein levels in the CSF and EEG abnormalities. These patients were   hypothyroid with positive antithyroid antibodies [1].  The  disorder  is  more  common  in  females,  with  female  to  male  ratio  being  4:1.  It  is  commonly  seen  during  the  fourth  decade  of  life,  but  can  appear  in  children  as  well  [2-4].

    Two major patterns of clinical manifestations have been reported: i)  25%  of  patients exhibit a stroke-like  pattern  of  multiple  recurrent  episodes  of  focal  neurologic  deficits with a variable  degree  of  cognitive  dysfunction  and  impaired  consciousness,  and  ii)  75%  present  with  a  diffuse  progressive pattern of slow cognitive  decline  with  dementia, confusion and hallucinations [2,5].  However, a third pattern was recently described by Watemberg et al.  as “relapsing-remitting manner including cognitive deterioration and psychiatric illness” [6]. These patients may experience focal or generalized tonic-clonic seizures  or  even  status  epilepticus. Other features include  myoclonus,  tremors,  hypereflexia,  psychosis, visual  hallucinations  and  paranoid  delusions  [2,3,5].

    The exact mechanism of HE remains unknown. The  most  probable  mechanisms   include  disseminated  encephalomyelitis  and/or autoimmune  general  cerebral  vasculitis  [1,6,7].  As  a  result  of  impaired  cerebral  perfusion  and  metabolism,  a  wide  range  of  symptoms  have  been  described  [8]. The  diagnosis  of  HE  requires  the  presence  of  elevated  levels  of  antithyroid  antibodies.   In  some  cases,  the  diagnosis  is  supported  by  the  presence  of  Hashimoto’s  thyroiditis  while  in  others  there  may  not  be  any  concomitant  thyroid  disorder.  However,  neither  the  clinical  stage  of  the  disease  nor  the  severity  of  the  neurological  symptoms  have  any  relation  with  the  concentration  of  these  antibodies.  These  antibody  titres  may  be  elevated  in  CSF  [2,3,9]. 

    A new autoimmune  antigen,  amino  terminal  of  alpha-enolase  (NAE),  was  found  in  the brain  of  HE  patients.  A  high  level  of  antibodies  against  this  antigen  was  also  found  in  these patients.  These  antibodies  were  not  detected  in  patients  with  other  neurological  diseases [10].  Studies  have  confirmed  the  high  specificity  of  NAE  in  HE,  and  together  with  antithyroid  antibodies,  it  can  be  a  useful  diagnostic  marker  for  HE  [11,12]. CSF  analysis,  EEG  and  MRI  brain  studies  do  not  show  consistent  findings  which  can  aid  in  the  diagnosis  of  HE.  Lymphocytic  pleocytosis  and  elevated  protein  levels  may  be  seen  in  the  CSF  analysis  of  HE  patients  [2,5].  A  nonspecific  slow  background  activity,  focal  spikes  or  sharp  waves  and  transient  epileptic  activity  are  some  of  the  EEG  abnormalities  [5,13].  The  MRI  brain  of  these  patients  can  be  normal or  may  show  ischemic  lesions,  demyelination,  vasogenic  edema  or  atrophy  [14].

    Due  to  the  cocktail  of  symptoms,  HE  can  masquerade  a  vast  number  of  conditions  like  stroke  or  transient  ischemic  attack,  cerebral  vasculitis,  carcinomatous  meningitis,  toxic  metabolic  encephalopathy, paraneoplastic syndromes,  Creutzfeldt-Jakob disease, degenerative  dementia and psychiatric diseases [2,3]. Once  the  diagnosis  of  HE  is  confirmed,  corticosteroids  form  the  mainstay  of  treatment [15].  Intravenous immunoglobulin has also been tried in certain cases [16]. Unlike myxodema coma, HE does not respond to thyroxine replacement [17].  The long-term prognosis is variable.  Most  of  the  patients  respond  to  the  treatment;  while  others  show  a  relapsing  or  progressive  pattern  [2,3].

Conclusion

HE is  a  rare disorder  probably  because  of  the  low  awareness  of  the  disease  or  due  to  its  masquerading features.  Hence,  while  dealing  with  a  patient  presenting  with  unexplained  encephalopathy,  the  possibility  of  HE  should  be  considered,  especially  in  the  presence  of  high  antithyroid  antibody  levels.  Since  the  disorder  is  autoimmune  in  nature,  initiation  of  corticosteroid  therapy  shows  dramatic  recovery.

Acknowledgements

It  is  my  genuine  pleasure  to  express  my  deep  sense  of  thanks  to  my  colleagues  Dr.Rohit,  Department  of  Neurology,  Dr. Biju  Mohan,  Department  of  Medicine,  and  Dr. Pavan  Maniyar,  Department  of  Radiology,  for  their  support  and  suggestions  and  all  the  staff  of  National  hospital,  Calicut  for  their  co-operation.  It  is  my  privilege  to  thank  my  parents  and  my  wife  for  all  their  moral  support,  and  above  all,  God  almighty,  without  who’s  blessings  nothing  is  possible.

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Manappallil RGHashimoto’s Encephalopathy: Is it a Rare Condition or a Masquerading One?.JCR 2015;5:490-493
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Manappallil RGHashimoto’s Encephalopathy: Is it a Rare Condition or a Masquerading One?.JCR [serial online] 2015[cited 2020 May 27];5:490-493. Available from: http://www.casereports.in/articles/5/2/Hashimotos-Encephalopathy.html
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