hashimoto’s encephalopathy presenting with multiple

IJCRI – International Journal of Case Reports and Images, Vol. 3 No. 5, May 201 2. ISSN – [0976-31 98]

IJCRI 201 2;3(5):31 –35.www.ijcasereportsandimages.com

Hashimoto’s encephalopathy presenting with multiplecranial nerve palsies and hemiparesis:A case reportSantanu Saha, Riddhi Das Gupta, Adreesh Mukherjee,Arijit Singha, Dhiman Das, Mrinal Kanti Roy

ABSTRACTIntroduction: Hashimoto’s encephalopathy is asteroidresponsive encephalopathy associatedwith elevated blood concentrations ofantithyroid antibodies. The patients are usuallyeuthyroid or mildly hypothyroid. A wide array ofclinical features of Hashimoto’s encephalopathyhas been reported till date. The pleomorphicmanifestations may be behavioral and cognitivechanges, myoclonus, seizures, pyramidal tractdysfunction, involuntary movements,cerebellar signs, psychosis and coma, withrelapsing and progressive course. The diagnosisis often overlooked at presentation but iscrucial, given that this is a treatable disease.Case Report: We describe a case of Hashimoto‘sencephalopathy presenting with multiplecranial nerve palsies and right sidedhemiparesis in a 32yearold male patient fromWest Bengal, India. Conclusion: This is the firstreported case of multiple cranial nerveinvolvement in a case of Hashimoto’sencephalopathy.Keywords: Hashimoto’s encephalopathy,Cranial, Palsies, Nerve, Multiple, Hemiparesis

*********Saha S, Gupta RD, Mukherjee A, Singha A, Das D, RoyMK. Hashimoto’s encephalopathy presenting withmultiple cranial nerve palsies and hemiparesis: A casereport. International Journal of Case Reports andImages 2012;3(5):31–35.

*********doi:10.5348/ijcri201205122CR7

INTRODUCTIONHashimoto's encephalopathy is an uncommonneurologic syndrome associated with Hashimoto'sthyroiditis. It was initially described in 1966 [1], and itremains a diagnostic conundrum. The cause ofHashimoto's encephalopathy is proposed to beautoimmune because of its association with otherimmunologic disorders (myasthenia gravis,glomerulonephritis, primary biliary cirrhosis, perniciousanemia and rheumatoid arthritis), femalepredominance, inflammatory findings in cerebrospinalfluid (CSF) and response to treatment with steroids [1,2]. Other authors suggest that Hashimoto'sencephalopathy may represent an autoimmune cerebralvasculitis resulting from either endothelialinflammation or immune complex deposition [13].Clinical findings are variable and nonspecific. Thevaried range of clinical presentations often lead to adelay in diagnosis and initiation of treatment. Althoughneurological presentations like confusion, dizziness,hemiparesis, paraesthesia and involuntary movementshave been documented, the involvement of multiplecranial nerves (CNs) was a hitherto unknown facet ofthis disease.In this case report, we present the case of a patientwith multiple cranial nerve involvement and right sidedhemiparesis due to Hashimoto’s encephalopathy.

CASE REPORT OPEN ACCESS

Santanu Saha1 , Riddhi Das Gupta1 , Adreesh Mukherjee1 ,Ari j it Singha1 , Dhiman Das1 , Mrinal Kanti Roy1

Affi l iations: 1Department of Medicine, Institute ofPostGraduate Medical Education and Research, SSKMHospital, 244 AJC Bose Road, Kolkata-700020, WestBengal, India.Corresponding Author: Riddhi Das Gupta, 1 03/1 9 NabaliaPara Road, Barisha, Kolkata-700008, West Bengal, India;Ph: +91 -801 71 44032; Email : riddhi_dg@rediffmail .com

Received: 1 6 September 2011Accepted: 23 December 2011Published: 31 May 201 2

Saha et al. 31



CASE REPORTA 32yearold male, nonsmoker, nonalcoholic, notknown to be a diabetic or hypertensive, presented to uswith sudden onset right sided hemiparesis anddeviation of angle of mouth to the left side for one day.This episode was preceded by hoarseness of voice anddifficulty in swallowing for a week. The hoarseness ofvoice was of sudden onset and nonprogressive in nature.He also had severe headache at the time of admission.There was no history of fever, vomiting, convulsions,neck rigidity or loss of consciousness. There was nohistory of drug intake or exposure to toxins. He did nothave any previous transient or permanent neurodeficit.He had normal bowel and bladder habits. There was nosimilar illness in any of his family members.On examination, the patient was confused withhoarseness of voice and slurred speech. There was rightsided hemiparesis with power 3/5 in right upper andlower limbs, tone was normal in all four limbs and allthe deep tendon reflexes were exaggerated. The plantarresponse was extensor on the right side. Doll’s eyephenomenon was present. There was right sided lowermotor neuron type of facial nerve palsy (Figure 1) alongwith bulbar weakness with right sided IX and X CNpalsy, absent gag reflex and a normal jaw jerk.Otorhinolaryngeal examination revealed right sided VIIIcranial nerve paralysis and ipsilateral vocal cordparalysis. There was no tongue abnormality.All routine investigations were essentially normal.ELISA for HIV was nonreactive. Further investigationsrevealed that Anti Nuclear Antibody (hep2 pattern),antidoublestranded DNA, antihepatitis B coreantigen, hepatitis B surface antigen, antihepatitis Cvirus, lupus anticoagulant and Venereal DiseaseResearch Laboratory test results were negative. Also,the anticardiolipin antibody IgG level was 10.8 U/GPL(normal, <23 U/GPL), anticardiolipin antibody IgM was5.9 U/MPL (normal, <11 U/MPL). The cerebrospinalfluid study was normal and showed no evidence of anybacterial, tuberculous viral or fungal infection. Thecomputed tomography (CT) scan (Figure 2) andmagnetic resonance imaging (MRI) scan (Figure 3) ofbrain were normal. Electroencephalography studieswere unremarkable.Keeping in mind the possibility of an autoimmuneetiology we went for a complete thyroid profileinvestigation including the serum antithyroidperoxidase antibody level estimation. The serum antiTPO was high >1300 U/ml (biological reference intervalof >60 U/ml considered positive). The serum FT4 andTSH were however normal. We then proceeded with ahighresolution USG of thyroid gland which showedheterogeneous nodular lesions in both lobes. FNACfrom thyroid gland nodule showed that the overallcytomorphological features were suggestive oflymphocytic autoimmune thyroiditis (Figure 4).Considering the clinical and laboratory findings, adiagnosis of “multiple cranial nerve palsies with rightsided hemiparesis due to Hashimoto’s encephalopathy”was made.

The patient was started on 1 gm methylprednisolone,administered intravenously daily over three days. Therewas a rapid clinical response. He was switched over tooral prednisone starting at 1 mg/kg daily, with a slowtaper. He came back for his routine check up after threeweeks and had experienced significant resolution ofsymptoms.

Figure 1: Left sided LMN facial palsy in the patient withHashimoto’s encephalopathy.

Figure 2: CT scan of brain showing no detectable abnormalityin this patient.

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DISCUSSIONHashimoto's encephalopathy is an unusualneurologic disorder whose etiology, pathogenesis andhistologic characteristics are unclear. A systematicreview published in 2003 [1] reported only 85 welldocumented cases in the literature; however, thissyndrome may be underrecognized. A hospitalbased

epidemiologic study of neurologic symptoms consistentwith HE estimated its prevalence to be about2.1/100,000 [4] . The disorder occurs more frequentlybetween age 44–46 years, with a femaletomale ratio of4:1. [1, 5].The clinical manifestations usually include acute tosubacute onset of confusion with alteration ofconsciousness. Two major patterns of presentation aredescribed: 1) 25% of patients follow a strokelike patternof multiple recurrent episodes of focal neurologic deficitswith a variable degree of cognitive dysfunction andconsciousness impairment [1, 2], and 2) the remaining75% present with a diffuse progressive pattern of slowcognitive decline with dementia, confusion andhallucinations [1, 2]. These two clinical patterns mayoverlap over the course of the disease. Twothirds ofpatients may experience focal or generalized tonicclonicseizures, and 12% may present with status epilepticus.Also, myoclonus or tremor is seen in up to 38% patients,hyperreflexia and other pyramidal tract signs in 85%patients and psychosis, visual hallucinations andparanoid delusions have been reported in 25–36%patients [1, 2, 5]. However, the presence of multiplecranial nerve palsies with hemiparesis is a unique andunreported presentation of this disease. Our case is thefirst such report to throw light on an unknownpresentation of HE.The mechanism of Hashimoto's encephalopathy doesnot appear to be related to the thyroid status, which canvary greatly in patients with this disease. In two recentreviews, 23–35% of patients had subclinicalhypothyroidism, 17–20% had hypothyroidism, 7% hadhyperthyroidism and 18–45% were euthyroid [1, 5]. Thedevelopment of neurologic symptoms may occur up tothree years before the onset of autoimmune thyroiditis[6].The presence of elevated serums levels of antithyroidantibodies remains an essential characteristic of HEdiagnosis, and suggests the presence of thyroidautoimmunity [1, 5]. Although in some cases, thediagnosis is supported by the association withHashimoto's thyroiditis, it is possible that some patientsdevelop HE without a concomitant clinical thyroiddisease because asymptomatic thyroid autoimmunity isfrequent in these patients [1, 5].The pathogenic role of thyroid antibodies remainsunknown. There is no evidence that any antithyroidantibody reacts with brain tissue or affects nervefunction and there is no clear correlation between theseverity of the neurologic symptoms and theconcentration of these antibodies [1, 4].Antithyroid antibodies have also been related toother autoimmune conditions such as myopathy,depression, bipolar disease and dementia, but theprevalence of these antibodies in the general population(range: 2–20%) makes it difficult to establish whether areal association exists [7].Infrequently, the titers of antithyroid antibodies(TPOAb and TgAb) are measured in the CSF. In one caseseries, nine of 12 patients with encephalopathy andelevated serum antithyroid antibodies had elevated CSF

Figure 3: MRI scan of brain showing no detectableabnormality in this patient.

Figure 4: FNAC with histopathological examination fromthyroid gland nodule suggestive of lymphocytic autoimmunethyroiditis.

Saha et al. 33



autoantibody titers [4]. A systematic review found that13% of published cases of HE reported antithyroidantibodies in the CSF [5]. However, the titers ofantithyroid antibodies in the CSF do not correlate withthe clinical stage of the disease, and the sensitivity andspecificity of this finding remain unclear [4, 5].An autoantibody against the amino terminal end ofthe enzyme αenolase, an antigen of the thyroid and thebrain, has been identified as a potential biomarker ofHashimoto's encephalopathy [5, 8]. A study foundserum autoantibody reactivity in five of six patients withHashimoto's encephalopathy compared with two of 17patients with Hashimoto's thyroiditis but noencephalopathy and in none of 25 healthy controlsubjects [8]. This antigen is also found in endothelialcells, suggesting an autoimmune vasculitic mechanism;however, this has not been confirmed by neuroimagingtechniques [5].In some patients, Creactive protein and theerythrocyte sedimentation rate are elevated [9], and inone series, mild elevation of liver enzymes was found in12 of 20 patients [9].Although the CSF analysis results were normal inour patient, a lymphocytic pleocytosis has been found in14% of reported patients; in 4% of patients, it maycontain more than 100 cells/mm3. An elevated proteinconcentration occurs in 78% patients; and in 20%patients, it may be greater than 100 mg/dL. The bloodglucose concentration is usually normal [1, 2].Nonspecific EEG abnormalities are seen in 90–98%patients, which is usually a nonspecific slow backgroundactivity. The same pattern was observed in our patient.Focal spikes or sharp waves and transient epilepticactivity are less common [2, 10].In a review of 82 patients with HE, brain computedtomography or MRI showed abnormalities in 49%patients as cerebral atrophy, focal cortical abnormality,diffuse subcortical abnormality and nonspecificsubcortical focal white matter abnormality.The differential diagnosis of Hashimoto'sencephalopathy must consider any condition associatedwith delirium, rapidly progressive dementia, seizures orfocal neurologic deficits [5]. Thus, the list of diseasesthat can be confused with HE is vast, including stroke ortransient ischemic attack, cerebral vasculitis,carcinomatous meningitis, toxic metabolicencephalopathies, paraneoplastic syndromes,CreutzfeldtJakob disease, degenerative dementia andpsychiatric diseases [1, 5].The longterm prognosis is variable, although a highpercentage of patients respond to treatment; others mayhave a progressive or a relapsing course [1, 5]. Thesymptoms usually improve with glucocorticoid therapy;however, it is not necessary. A systematic review of 85published cases of Hashimoto's encephalopathy foundclinical response in 98% patients treated withglucocorticoids, 92% patients treated withglucocorticoids and levothyroxine and 67% of patientstreated with levothyroxine only [1].

CONCLUSIONHashimoto's encephalopathy frequently presentswith a myriad of neurological symptoms and normalfindings in several different examinations. Thissyndrome may go unrecognized for a long time and thepatient may be subjected to numerous investigationswithout definite benefit. Our case report uncovers a veryunusual presentation of Hashimoto’s encephalopathy inthe form of multiple cranial nerve palsies with righthemiparesis. Henceforth, this presentation if kept inmind while evaluating patients with a diagnosticdilemma, might help in instituting early and correcttreatment.

*********Author ContributionsSantanu Saha – Substantial contributions to conceptionand design, Drafting the article, revising it critically forimportant intellectual content, Final approval of theversion to be publishedRiddhi Das Gupta – Substantial contributions toconception and design, acquisition of data, Drafting thearticle, revising it critically for important intellectualcontent, Final approval of the version to be publishedAdreesh Mukherjee – Substantial contributions toconception and design, analysis and interpretation ofdata, Drafting the article, revising it critically forimportant intellectual content, Final approval of theversion to be publishedArijit Singha – Substantial contributions to conceptionand design, acquisition of data, Drafting the article,Final approval of the version to be publishedDhiman Das – Substantial contributions to conceptionand design, analysis and interpretation of data, Draftingthe article, Final approval of the version to be publishedMrinal Kanti Roy – Substantial contributions toconception and design, analysis and interpretation ofdata, Drafting the article, Final approval of the versionto be publishedGuarantorThe corresponding author is the guarantor ofSubmission.Conflict of InterestThe authors declare no conflict of interest.Copyright© Santanu Saha et al. 2012; This article is distributedunder the terms of Creative Commons attribution 3.0License which permits unrestricted use, distributionand reproduction in any means provided the originalauthors and original publisher are properly credited.(Please see www.ijcasereportsandimages.com/copyrightpolicy.php for more information.)

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hashimoto’s encephalopathy presenting with multiple

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