
==== Front
Ann Indian Acad Neurol
Ann Indian Acad Neurol
AIAN
Ann Indian Acad Neurol
Annals of Indian Academy of Neurology
0972-2327
1998-3549
Wolters Kluwer - Medknow India

AIAN-27-463
10.4103/aian.aian_206_24
Letters to the Editor
Palatal Tremor, Periocular and Perioral Myokymia, and Pseudoathetosis in a Patient with Whipple’s Disease
Jha Vaidehi
Makharia Archita
Garg Divyani
Agarwal Ayush
Radhakrishnan Divya M.
Pandit Awadh Kishor
Srivastava Achal Kumar
Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
Address for correspondence: Dr. Divyani Garg, CardioNeuro Center, All India Institute of Medical Sciences, Room 705, New Delhi - 110 029, India. E-mail: divyanig@gmail.com
Jul-Aug 2024
18 7 2024
27 4 463464
18 3 2024
13 5 2024
02 6 2024
Copyright: © 2024 Annals of Indian Academy of Neurology
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
==== Body
pmcDear Editor,

Whipple’s disease (WD) is a rare systemic disorder caused by the gram-positive bacillus Tropheryma whipplei. It primarily manifests as malabsorption in the gastrointestinal tract and may also affect the central nervous, cardiovascular, and skeletal systems.[1] We report a patient uncommonly presenting with palatal tremor and ocular and perioral myokymia in the setting of sensorimotor neuropathy, arthralgias, and anemia as manifestations of WD.

A 53-year-old farmer presented with intermittent migratory polyarthralgias for 2.5 years, predominantly involving large joints. There was no obvious redness or swelling in the joints. He also reported paresthesia, which started initially in bilateral lower limbs and progressed proximally up to the knees, and subsequently involved both hands over the preceding 2 years. He reported intense allodynia in these regions. He had associated fatigue and had noted tremulousness involving both upper limbs for the past 6 months. He was a hypertensive on treatment. He also reported long-standing dyspepsia and postprandial bloating. He had experienced observable weight loss over the past 1 year, which was unquantified. Family history was not significant.

On general examination, he was observed to have pitting pedal edema up to the mid-shin, pallor, and hepatosplenomegaly. Higher mental functions were normal. He was observed to have a palatal tremor [Video 1], perioral and periocular myokymia, and pseudoathetosis. Oculomotor examination was normal. Motor examination revealed bilateral symmetrical wasting of distal limbs and hypotonia of all limbs. He had weakness in all limbs, involving distal more than proximal limb musculature. Deep tendon reflexes were absent. Sensory examination showed impaired touch, pain, temperature, vibration, and joint position sense distal to the knees and wrists. Cerebellar examination showed bilateral dysdiadochokinesia, impaired heel–knee–shin and finger–nose–finger tests, dysmetria, and intentional tremors. The patient could not ambulate without support and had an ataxic gait. Romberg’s sign was positive.

Routine investigations showed microcytic anemia (hemoglobin [Hb] 10.4 mg/dL), elevated erythrocyte sedimentation rate and C-reactive protein. Magnetic resonance imaging of the brain and spine was normal. Nerve conduction studies showed severe sensory motor neuropathy (nonrecordable). Surface electromyography showed myokymia involving the left orbicularis oculi. Cerebrospinal fluid (CSF) analysis showed five cells (all lymphocytes), protein 226 mg/dL, and sugar 65 mg/dL (concomitant serum glucose 139 mg/dL). Ultrasound abdomen revealed hepatosplenomegaly. Whole body positron emission tomography scan was normal. Paraneoplastic and autoimmune workups, vasculitis profile, human immunodeficiency virus, anti-HbsAg, anti-HCV, venereal disease research laboratory serology, and anti-tissue transglutaminase serology were negative. In view of anemia and organomegaly, paraproteinemia was also considered; abdominal fat pad, serum protein electrophoresis and immunoelectrophoresis, and serum free light chain assay were normal. CSF polymerase chain reaction (PCR) was positive for T. whipplei. Duodenal biopsy showed duodenitis, but no evidence of foamy macrophages. The patient was started on injection ceftriaxone 2 g/day for 2 weeks followed by maintenance therapy with hydroxychloroquine and cotrimoxazole. At 6 months of follow-up, the patient reported stabilization of symptoms. A repeat CSF was done at 6 months, which showed acellular CSF with negative PCR for T. whipplei. The patient continues to be on maintenance therapy.

WD is a rare systemic disease affecting 1–3 per million persona and is more common in males than females (ratio 4:1).[2] T. whipplei is a gram-positive Actinobacterium which is soil dwelling; hence, the disease is more common in farmers[3] and is associated with the human leukocyte antigen-B27 haplotype.[4] The bacteria travel via lymphatic channels to the lymph nodes and finally enter the bloodstream, causing systemic damage. WD is a multisystemic disorder affecting joints, skin, lymphatics, cardiac, pulmonary, ocular, and nervous systems. There are three characteristic manifestations of this disease: (i) classic Whipple’s disease including migratory polyarthralgias (first stage); abdominal symptoms including diarrhea, weight loss, abdominal pain (second stage); a generalized stage with pulmonary, cardiovascular, and neurologic manifestations which include abnormal movements, typically oculomasticatory myorhythmia and ataxia (third stage); (ii) localized chronic infections, predominantly endocarditis; and (iii) acute infections, for example, pneumonia, gastroenteritis, etc.[5]

Neurologic manifestations of WD are myriad and include cognitive impairment, psychiatric abnormalities, ataxia, seizures, neuropathy, and myorhythmia [Figure 1]. In the present case, the patient had unique neurologic manifestations of WD in the form of palatal tremor, ocular and periorbital myokymia, and pseudoathetosis arising from a severe neuropathy. Myokymia is defined as a wormlike, undulating, and rippling movement of muscles. Myorhythmia is a regular, repetitive, and slow movement affecting the limb or cranial musculature, and has a frequency of 1–4 Hz. Hepatosplenomegaly was a clue in this patient. Accumulation of these foamy macrophages and granulomatous reaction in the liver and spleen may lead to their enlargement.[67] Palatal tremor and myokymia are manifestations of neurologic deterioration seen in WD. The bacteria can infiltrate the central nervous system, forming lesions that can disrupt descending motor pathways, causing palatal myoclonus, weakness, and ocular and periorbital myokymia.[8] In a systematic review of movement disorder abnormalities associated with WD, the authors reported them to be “extremely rare” in WD.[9] In two patients, the term palatal myorhythmia was used to describe the palatal movements. Lack of olivary involvement on neuroimaging has been noted in a previous case with palatal tremor in the setting of WD.[9] Movement disorders in WD are myriad.[9] These include oculomotor abnormalities, comprising convergence–divergence myorhythmia or vertical nystagmus, which may be associated with oculomasticatory, palatal, or facioskeletal myorhythmia, or may occur in an isolated manner. Other movement disorders include other myoclonus (segmental or focal), ataxia, parkinsonism, tremor, dystonia, and chorea.

Figure 1 Neurologic manifestations of Whipple’s disease

This case highlights the variety of movement disorders that may be seen in WD, which represents a treatable cause of infection-related movement disorders. Systemic clues, including anemia, migratory polyarthralgias, and hepatosplenomegaly, may further route the diagnostic pathway.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his names and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Video available on: https://journals.lww.com/annalsofian
==== Refs
REFERENCES

1. Kukull B Mahlow J Hale G Perry LJ Whipple’s disease: A fatal mimic Autops Case Rep 2021 11 e2020237 34277495
2. Biagi F Balduzzi D Delvino P Schiepatti A Klersy C Corazza GR Prevalence of Whipple’s disease in north-western Italy Eur J Clin Microbiol Infect Dis 2015 34 1347 8 25804189
3. Antunes C Singhal M Whipple disease StatPearls Treasure Island (FL) StatPearls Publishing 2023
4. Feurle GE Dörken B Schöpf E Lenhard V HLA B27 and defects in the T-cell system in Whipple’s disease Eur J Clin Invest 1979 9 385 9 93049
5. Dolmans RA Boel CH Lacle MM Kusters JG Clinical manifestations, treatment, and diagnosis of tropheryma whipplei infections Clin Microbiol Rev 2017 30 529 55 28298472
6. Desnues B Ihrig M Raoult D Mege JL Whipple’s disease: A macrophage disease Clin Vaccine Immunol 2006 13 170 8 16467322
7. Kuftinec G Deshpande AR Carrion AF Hepatobiliary manifestations of Whipple disease Clin Liver Dis (Hoboken) 2021 17 180 3 33868662
8. Deriaz S Grouille J Puéchal X Oculomasticatory myorhythmia in Whipple’s disease Lancet Rheumatol 2020 2 e446 38273606
9. Bally JF Méneret A Roze E Anderson M Grabli D Lang AE Systematic review of movement disorders and oculomotor abnormalities in Whipple’s disease Mov Disord 2018 33 1700 11 30338868
