Movement disorder associated with celiac disease and thyroid dysfunction:case report

Pakistan Journal of Neurological Pakistan Journal of Neurological

Sciences (PJNS) Sciences (PJNS)

Volume 15 Issue 2 Article 9

6-2020

Movement disorder associated with celiac disease and thyroid Movement disorder associated with celiac disease and thyroid

dysfunction:case report dysfunction:case report

Ramla Nayaib Hashmi

Neurologist,Rabia Moon Institute Of Neurosciences, Karachi. 2.

Ummul Kiram

Saifee and Mamji Hospital , Karachi

Rabbia Tariq

,The Indus Hospital , Karachi

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Recommended Citation Recommended Citation

Hashmi, Ramla Nayaib; Kiram, Ummul; and Tariq, Rabbia (2020) "Movement disorder associated with

celiac disease and thyroid dysfunction:case report,"

Pakistan Journal of Neurological Sciences (PJNS)

Vol. 15 : Iss. 2 , Article 9.

Available at: https://ecommons.aku.edu/pjns/vol15/iss2/9

MOVEMENT DISORDER ASSOCIATED WITH CELIAC

DISEASE AND THYROID DYSFUNCTION:CASE REPORT

PAKISTAN JOURNAL OF NEUROLOGICAL SCIENCES

VOL. 15 (2) APRIL-JUNE 2020

ABSTRACT:

Autoimmune movement disorders are uncommon yet likely treatable conditions. It is challenging to diagnose and

manage these disorders, ultimately leading to a significant morbidity in terms of functional disability of patient. It is

troublesome for practicing neurologists to identify whether the antibodies which are detected during the work up of

these autoimmune movement disorders are merely incidental or have pathogenic role. This will help them to decide

regarding whether to start immunotherapy or not. Here we have discussed two patients of movement disorder who

were found to have positive work up for other autoimmune diseases. Available Literature on autoimmune movement

disorder is very limited and further research on large scale is needed.

KEY WORDS: Autoimmune movement disorder, autoimmune dystonia, gluten ataxia, celiac disease, thyroid

dysfunction

BACKGROUND: Autoimmune movement disorders comprises of a widespread group of neurologic disorders which

occur either in isolation or along with more diffuse autoimmune illnesses. The exact incidence and prevalence of

autoimmune movement disorders is not known as it’s a rare disorder and very limited data is available on it comprising

of few case reports or small sample studies. One estimates suggest that all autoimmune diseases combined affect

about 3% of the US population, thus approximately 10 million people.

Many movement disorders occur due

pathologic alterations in the basal ganglia or their connections including caudate, putamen, and pallidum ,

subthalamic nucleus, substantia nigra, pedunculopontine nucleus, although some exceptions can be present. Due to

the fact that pure, isolated autoimmune movement disorders are uncommon, work up for other aetiologies is strongly

recommended.

Any movement disorder phenomenology can occue in these disorders and many of the presentations

can mimic neurodegenerative disorders, such as Huntington disease. Disorders may be ataxic, hypokinetic

(Parkinsonism), or hyperkinetic (myoclonus, chorea, and other dyskinetic disorders

3,4

Movement disorders are commonly detected in autoimmune diseases. Chorea may present in patients with

anti-NMDAR encephalitis, Sydenham disease, lupus and anti-phospholipid syndrome. Dystonic seizures and

neuromyotonia may precede autoimmune encephalitis. Anti-glycine antibodies are encountered in the pathogenesis of

progressive encephalomyelitis presenting with rigidity and myoclonus. Hashimoto's encephalitis and

opsoclonus-myoclonus syndrome have commonly tremor and myoclonus. Few case reports and review articles also

highlight the association of Celiac disease and autoimmune thyroid disorders with autoimmune movement disorders

Celiac disease (CD) approximately accounts for up to 10% of neurological manifestations irrespective to the

presence of malabsorption symptoms

According to an article published in 2018, in patients with autoimmune

disorders affecting the central and peripheral nervous system, movement disorder are frequent. They may be found in

autoimmune disorders incited by an infectious agent, like streptococcus in Sydenham's chorea, or in basal ganglia

encephalitis with antibodies against the dopamine-D2 receptors.In these scenarios, chorea or dystonia are usually the

most prominent.In diffuse or limbic encephalitis with antibodies directed against neuronal cell-surface antigens ,

patients also have MD. Anti-NMDA receptor encephalitis is one of the most common and may present with a variety

of MDs, including: chorea, stereotypies, dystonia and myorhythmia while in stiff-person syndrome or cerebellar ataxia

, intracellular enzyme glutamic acid decarboxylase are found most commonly.

Clues of when to suspect an

autoimmune etiology are Female patient , Subacute onset, variable course of disease , neurological disease with

multiple foci , autoimmunity personal or family history , Patient having history of cancer or suspicion of new cancer

,Abnormal laboratory supportive tests, i.e., Cerebrospinal fluid , imaging and the response to immunotherapy.

A rapid

diagnosis of an autoimmune disorder is utmost as early therapeutic intervention improves long-term prognosis and

Correspondence to: Ramla Nayaib Hashmi Email:[email protected]

Date of submission: February 17, 2020 Date of revision: March 28, 2020 Date of acceptance: April 09, 2020

Dr. Ramla Nayaib Hashmi

, Dr. Ummul Kiram

, Dr.Rabbia Tariq

Consultant Neurologist,Rabia Moon Institute Of Neurosciences, Karachi.

Consultant Neurologist,Saifee and Mamji Hospital , Karachi.

Post graduate (MCPS) Trainee,Family Medicine Department ,The Indus Hospital , Karachi.

CASE REPORT

may be life-saving. Treatment usually comprises of some form of immunotherapy and symptomatic therapy of the

abnormal movements with dopamine depleters, dopamine receptor antagonists, or GABAergic drugs. Early-initiated

immunotherapy leads to the best possible outcomes. Moreover, depending on the antibody profile, a search for cancer

may be necessary followed by removal of an underlying tumour for optimal outcome.

3,4

It is challenging to diagnose

such autoimmune disorders due to the delayed clinical suspicion, improper approach to get the relevant systematic

work up and lack of facilities for specific antibodies detection or in paraneoplastic cases getting extensive work up for

occult neoplasm. The whole work up is expensive and time consuming ending mostly in lost to follow up of patients.

For instance, in literature, work up suggested for autoimmune movement disorder include CRMP-5, ANNA-1 (Hu),

ANNA-2 (Ri), GAD65, VGCC antibodies for chorea, ANNA-2 (Ri), CRMP-5, NMDA-R, GAD65, DPPX antibodies for

myoclonus, NMDA-R for dyskinesia ,LGI1, GAD65 for Parkinsonism,GAD65, DPPX, Amphiphysin for Stiff-Person

Spectrum Disorders,ANNA-1 (Hu), PCA-1 (Yo), GAD65, VGCC, CASPR2, mGluR1, DPPX for ataxia

3,4

Despite all these

limitations in diagnosis, early management is very important.

CASE 1:

26 years old female patient with no known previous comorbid, married, mother of 2 children up and about till 2 years

back. She had history of fever 2 years back which was intermittent, high grade for which she was treated empirically.

Fever subsided in few days but she started complaining of difficulty in speech, tremors of neck and upper limbs along

with paroxysmal abnormal involuntary twisting and posturing of limbs characterized as dystonic posturing of limbs. Her

tremors were characterized as rhythmical oscillatory abnormal involuntary movements of neck in horizontal direction

present at rest while with action and intention becomes increased in amplitude and frequency. Her symptoms

progressively increased and she started having vertigo and limb and truncal ataxia leading to difficulty in walking. No

family history of any neurological disease. Her work up showed Hemoglobin ( Hb) 10.6 g/dl (12-15 g/dl) with normal

total leukocyte count (TLC ) and Platelet count , Erythrocytic sedimention rate (ESR ) 55 mm/Ist hour(0-25 mm/hr).

Peripheral film showed hypochromia, anisocytosis and poikilocytosis. Thyroid profile repeatedly showed low Thyroid

stimulating hormone TSH 0.16 microunit /ml(0.25-4.0 microunits/ml) with normal Free triiodothyronine (Free T3) and

Free Thyroxine (Free T4 levels). Patient had complaints of palpitations, weight loss and tremors which favours her

thyroid disorder. As she had symptomatic thyroid disorder, possibility of sick euthyroidism is ruled out. Her thyroglobulin

autoantibodies and thyroid peroxidase autoantibodies turned out negative. Ultrasound thyroid gland showed slightly

enlarged both lobes of thyroid glands with non-homogenous texture. Findings concluded as diffuse goiter most

probably associated with thyroiditis. Antinuclear antibodies (ANA) profile (which include ANA, antimitochondrial

antibodies (AMA, anti smooth muscle antibodies ASMA) and Anti-double stranded DNA antibodies (AntiDsDNA) were

negative. Vitamin B12 level was 626 pg/ml (181-906 pg/ml ). Wilson disease work up was negative including serum

ceruloplasmin level and 24 hours urinary copper. Creatine phosphokinase (CPK) level normal. Patient had history of

occasional diarrhoea and undocumented weight loss for 2 to 3 years. Anti - tissue transglutaminase Ig A reactive while

Anti tissue transglutaminase IgG non- reactive. MRI brain showed prominence of cerebellar folia and dilatation of fourth

ventricle consistent with cerebellar degeneration and atrophy. Repeat MRI brain after 8 months showed

re-demonstration of findings of cerebellar atrophy. Patient was started on amantadine 100 mg twice daily

,trihexiphenydyl 2 mg twice daily titrated to thrice daily dose, propranolol 10 mg thrice daily , vitamin E 600 mg twice

daily and supportive treatment along with rehabilitation including gait training and balancing exercises. Gluten free diet

was advised. Endocrinology review was taken for thyroiditis who started prednisolone 1 mg/kg/day. After 4 weeks of

follow up patient showed some improvement in her tremors, ataxia and dystonia.

CASE 2:

35 years old male patient of average height and weight presented with continual abnormal involuntary , non

rhythmical, non-stereotypical movement of tongue and jaw with some twisting and posturing characterized as

oromandibular dystonia, slurred speech consistent with dysarthia, bradykinesia (slowness of movements), and

difficulty in walking along with right leg dystonic posturing for last 2 years. No family history of any neurological

complaint. He did not use any antipsychotic. No symptoms of hypothyroidism, myopathy and malabsorption were

present on detailed history. His work up showed normal Complete blood count (CBC), ESR 5 mm/hr (0-25 mm/hr).

TSH 68.90 microunits/ml (0.25-4.0 microunits/ml) , FT3 1.93 pg/ml (2.0-4.25 pg/ml), FT4 0.01 pg/ml (7- 18 pg/ml)

Anti thyroid peroxidase antibodies (Anti TPO) > 1000.0 IU/ml means highly positive (<5.61IU/ml), Vitamin B12

136pg/ml (181-906 pg/ml )which was replaced , vitamin D level 18.0 ng/ml ( upto 30 ng/ml), CPK level of 3330 U/L

PAKISTAN JOURNAL OF NEUROLOGICAL SCIENCES

VOL. 15 (2) APRIL-JUNE 2020

PAKISTAN JOURNAL OF NEUROLOGICAL SCIENCES

VOL. 15 (2) APRIL-JUNE 2020

(male 24 -195 U/L)which on repeat testing found to be 10,400 U/L ,anti Transglutaminase IgG 0.304 ( cut off 0.304

by ELISA) and IgA 0.316 (cut off O.212 by ELISA ) were positive ,Fasting lipid profile serum cholesterol 221 mg

%(<200 mg%) LDL 151 mg% (upto 100 mg %). His serum ceruloplasmin 0.29 g/L (male 0.15-0.30 g/L), 24 hours

urinary copper 48 ug/day (<60 ug/day), SGPT 32U/L (<40 U/L). ANA was positive. Magnetic resonance imaging (MRI)

brain showed prominence of the cortical sulci and ventricles representing brain involution not corresponding to

patient’s age (figure 1) .Patient was on thyroxin 100 ug per day , levodopa/carbidopa 25/250 mg half tablet thrice a

day (TDS) and trihexiphenidyl 2 mg half TDS titrated upto 2 mg TDS ,Baclofen 10 mg half BD titrated gradually to 1

TDS along with rehabilitation . After a follow up of 4 weeks, his oromandibular dystonia improved to some extent but

no significant improvement in his leg dystonia and bradykinesia .Whether patient should be started on glutein free diet

as he was asymptomatic for coeliac disease and immunotherapy on the basis of work up or not to improve patient’s

dystonia was still undecided. According to the available literature patient was planned for immunotherapy with regular

follow up of his symptoms for the response.

FIGURE 1: MRI T2W image of case 2 showing prominence of the cortical sulci and

ventricles representing brain involution not corresponding to patient’s age (Blue arrows)

.Hyper intense signal are seen in bilateral basal ganglia (Red arrows).

DISCUSSION

Autoimmune movement disorders in neurology are emerging and likewise the associated

autoantibodies which need to be worked up. A number of essential tests as the supportive

evidence are recommended to be performed in case of suspected autoimmune movement

disorder. Antibody-related dystonia differs from primary dystonia, as it follows a characteristic

pattern in body parts affected and age at onset. In a patient with adult onset dystonia,

secondary causes of dystonia are more common. Work up is needed for the secondary causes

which turned out to be autoimmune in origin as our patient had significant abnormalities in work up which suggest a

systemic autoimmune involvement. Antibody associated dystonia typically presents as a combined dystonia means in

combination with further clinical signs, in particular encephalopathy

Neurodegeneration as evident on MRI brain of

my case 2 patient with OMD and limb dystonia is supporting this feature. Moreover he was asymptomatic for celiac

disease and thyroid disorder and surprisingly had very high CPK without any evidence of myopathy.

American academy of neurology published a small study in 2019 comprising of 4 patients diagnosed with autoimmune

dystonia. Generalized asymmetric dystonia was the most common presentation, and parkinsonian symptoms (rigidity

and resting tremors) were present in 1 patient. serum and cerebrospinal autoimmune encephalitis work up were

inconclusive. All patients were treated with Immunotherapy using intravenous methylprednisolone 1 g daily for 5 days

and intravenous immunoglobulin 0.4 gm/kg for 5 days, followed by azathioprine maintenance dose (2 mg/kg).

Improvement was found in all cases with complete resolution of autoimmune dystonia in 2 cases. Hence, it was

concluded that despite a significant delay in therapy due to misdiagnosis, autoimmune dystonia patients may respond

well to immunomodulators with an encouraging outcome

. Among the disorders associated with autoimmune disease

, Celiac disease (CD) is emerging as being frequently reported with significantly increased prevalence in individuals

with CD and their first-degree relatives as compared to controls

11-13

.The estimated burden of Autoimmune disease

(AD) in CD cases up to 15%

.It has a wide clinical spectrum which includes specific features of malabsorption with

diarrhoea, non-specific extra intestinal features, subclinical or asymptomatic variants , and likely disease

characterized by positive serology with a normal biopsy of intestinal mucosa

14,15

. The risk factors for developing other

AD are an early diagnosis and a positive family history of autoimmunity, whereas the gluten-free diet (GFD) has a

beneficial role

. Another article concluded that autoimmune movement disorders with an extracellular antibody and

without cancer are more likely to respond to treatment while the disorders with a cancer and/or an intracellular

antibody respond less well to immunotherapy

.Furthermore, while a GFD is found to improve and reverse symptoms

of gluten-associated ataxia and is an established therapy for CD, it is not the case with oromandibular dystonia (OMD).

CD has been found increasingly in patients with autoimmune thyroid disease i.e. Grave’s disease and Hashimoto’s

thyroiditis ,having a 2% to 7% prevalence

.Several mechanisms are suggested about the co-occurrence of CD and

autoimmune thyroid disease like similar genetic predisposition and both having the gene encoding cytotoxic

T-lymphocyte-associated antigen .In addition, tTG2 IgA antibodies has been shown to react with thyroid tissue, leading

to the development of thyroid disease in CD.In our both cases patients had positive work up for celiac disease as well

as had evidence of thyroid dysfunction along with the movement disorder.

References:

1.(https://pathology.jhu.edu/autoimmune/prevalence)

( john hopkin’s medicine)

2. Conor Fearon, Orna O’Toole.Autoimmune Movement

Disorders. Semin Neurol 2018; 38:316–329.

3. Honorat JA, McKeon A: Autoimmune movement

disorders: a clinical and laboratory approach. Curr

Neurol Neurosci Rep. 2017;17(1):4. doi:

10.1007/s11910-017-0709-2.

4. Jones AL, Flanagan EP, Pittock SJ, et al. Responses

to and outcomes of treatment of autoimmune

cerebellar ataxia in adults. JAMA Neurol.

2015;72(11):1304–1312. doi:10.1001/

jamaneurol.2015.2378.)

5. Lauret E, Rodrigo .Celiac Disease and

Autoimmune-Associated Conditions. BioMed Research

International Volume2013,Article ID 127589, 17

pages http://dx.doi.org/10.1155/2013/127589.

6. https://doi.org/10.14802/jmd.16063 / J Mov

Disord 2017;10(2):105-107 pISSN 2005-940X /

eISSN 2093-493)

7.Donaldson I, Marsden CD,Schneider S. Marsden’s

Book of Movement Disorders. Oxford: Oxford University

Press; 2012.

8 . Baizabal-Carvallo JF, Jankovic J .Autoimmune

and paraneoplastic movement disorders: An

update. REVIEW ARTICLE| VOLUME 385,

P175-184, FEBRUARY 15, 2018.

DOI:https://doi.org/10.1016/j.jns.2017.12.035

9 . Gövert F, Leypoldt F , Wandinger KP et al.

Antibody-related movement disorders – a

comprehensive review of phenotype autoantibody

correlations and a guide to testing Neurological

Research and Practice (2020) 2:6

https://doi.org/10.1186/s42466-020-0053-x

10.American academy of neurology ( April 09, 2019;

92 (15 Supplement) MAY 6, 2019) .

11.F.Cataldo and V.Marino, “Increased prevalence of

autoimmune diseases in first-degree relatives of

patients with celiac disease,” Journal of Pediatric

Gastroenterology and Nutrition,vol.36,no.

4,pp.470–473,2003.

12. M. Viljamaa, K. Kaukinen, H. Huhtala, S.

Kyr¨onpalo, M. Rasmussen, and P. Collin, “Coeliac

disease, autoimmune diseases and gluten

exposure,”Scandinavian Journal of Gastroenterology,

vol.40,no.4,pp.437–443,2005.

13. S. L. Neuhausen, L. Steele, S. Ryan et al.,

“Co-occurrence of celiac disease and other

autoimmune diseases in celiacs and their first-degree

relatives,” Journal of Autoimmunity,vol.31, no.

2,pp.160–165,2008.

14. P. Collin, T. Reunala, E. Pukkala, P. Laippala, O.

Keyril¨ainen, and A. Pasternack, “Coeliac

disease—associated disorders and

survival,”Gut,vol.35,no.9,pp.1215–1218,1994.

15. A. Fasano, I. Berti, T. Gerarduzzi et al.,

“Prevalence of Celiac disease in at-risk and

not-at-risk groups in the United States : a large

multicentre study, ”Archives of Internal

Medicine,vol.163, no.3,pp.286–292,2003.

16 .J. Cosnes, C. Cellier, S. Viola et al., “Incidence of

autoimmune diseases in celiac disease: protective

effect of the gluten-free diet,” Clinical

Gastroenterology and Hepatology,vol.6,no.7,pp.

753–758,2008.

PAKISTAN JOURNAL OF NEUROLOGICAL SCIENCES

VOL. 15 (2) APRIL-JUNE 2020

In 2017, “Isolated Neurological Manifestation in Silent Celiac Disease” was published in which a case of idiopathic

oromandibular dystonia (OMD) is discussed that was unresponsive to traditional symptomatic therapy. However,

complete resolution of symptoms was obtained after celiac disease (CD) diagnosis and gluten free diet

. In the same

way, our case 1 patient also showed the improvement. Association of asymptomatic high creatine phosphokinase

(CPK) level and celiac disease or other neurological illnesses remains unexplained except for the limited clue due to

its types CK MM, CK BB, and CK MB. Further studies are highly recommended to clarify the unexplained factors and

further management of such cases.

CONCLUSION:

Isolated autoimmune movement disorders are uncommon and are usually associated with other neurological features.

A prompt and thorough work up for an underlying cause and associated neural or systemic antibodies in such

suspected cases. Ultimately through this approach decisions can be easily taken for the treatment and prognosis of

disease. Further studies are direly needed to clarify the issues encountered in management of such cases.

References:

1.(https://pathology.jhu.edu/autoimmune/prevalence)

( john hopkin’s medicine)

2. Conor Fearon, Orna O’Toole.Autoimmune Movement

Disorders. Semin Neurol 2018; 38:316–329.

3. Honorat JA, McKeon A: Autoimmune movement

disorders: a clinical and laboratory approach. Curr

Neurol Neurosci Rep. 2017;17(1):4. doi:

10.1007/s11910-017-0709-2.

4. Jones AL, Flanagan EP, Pittock SJ, et al. Responses

to and outcomes of treatment of autoimmune

cerebellar ataxia in adults. JAMA Neurol.

2015;72(11):1304–1312. doi:10.1001/

jamaneurol.2015.2378.)

5. Lauret E, Rodrigo .Celiac Disease and

Autoimmune-Associated Conditions. BioMed Research

International Volume2013,Article ID 127589, 17

pages http://dx.doi.org/10.1155/2013/127589.

6. https://doi.org/10.14802/jmd.16063 / J Mov

Disord 2017;10(2):105-107 pISSN 2005-940X /

eISSN 2093-493)

7.Donaldson I, Marsden CD,Schneider S. Marsden’s

Book of Movement Disorders. Oxford: Oxford University

Press; 2012.

8 . Baizabal-Carvallo JF, Jankovic J .Autoimmune

and paraneoplastic movement disorders: An

update. REVIEW ARTICLE| VOLUME 385,

P175-184, FEBRUARY 15, 2018.

DOI:https://doi.org/10.1016/j.jns.2017.12.035

9 . Gövert F, Leypoldt F , Wandinger KP et al.

Antibody-related movement disorders – a

comprehensive review of phenotype autoantibody

correlations and a guide to testing Neurological

Research and Practice (2020) 2:6

https://doi.org/10.1186/s42466-020-0053-x

10.American academy of neurology ( April 09, 2019;

92 (15 Supplement) MAY 6, 2019) .

11.F.Cataldo and V.Marino, “Increased prevalence of

autoimmune diseases in first-degree relatives of

patients with celiac disease,” Journal of Pediatric

Gastroenterology and Nutrition,vol.36,no.

4,pp.470–473,2003.

12. M. Viljamaa, K. Kaukinen, H. Huhtala, S.

Kyr¨onpalo, M. Rasmussen, and P. Collin, “Coeliac

disease, autoimmune diseases and gluten

exposure,”Scandinavian Journal of Gastroenterology,

vol.40,no.4,pp.437–443,2005.

13. S. L. Neuhausen, L. Steele, S. Ryan et al.,

“Co-occurrence of celiac disease and other

autoimmune diseases in celiacs and their first-degree

relatives,” Journal of Autoimmunity,vol.31, no.

2,pp.160–165,2008.

14. P. Collin, T. Reunala, E. Pukkala, P. Laippala, O.

Keyril¨ainen, and A. Pasternack, “Coeliac

disease—associated disorders and

survival,”Gut,vol.35,no.9,pp.1215–1218,1994.

15. A. Fasano, I. Berti, T. Gerarduzzi et al.,

“Prevalence of Celiac disease in at-risk and

not-at-risk groups in the United States : a large

multicentre study, ”Archives of Internal

Medicine,vol.163, no.3,pp.286–292,2003.

16 .J. Cosnes, C. Cellier, S. Viola et al., “Incidence of

autoimmune diseases in celiac disease: protective

effect of the gluten-free diet,” Clinical

Gastroenterology and Hepatology,vol.6,no.7,pp.

753–758,2008.

Conflict of interest: There is no conflict of interest..

Funding disclosure: Nil

Author’s contribution:

Ramla Nayaib Hashmi; data collection, data analysis, manuscript writing, manuscript review

Ummul Kiram; data analysis,manuscript writing, manuscript review

Rabbia Tariq; data analysis, manuscript writing, manuscript review

PAKISTAN JOURNAL OF NEUROLOGICAL SCIENCES

VOL. 15 (2) APRIL-JUNE 2020