Acanthamoeba Encephalitis Presenting as Rapidly Developing Parkinsonism—A Wolf in Sheep's Clothing

Secondary parkinsonism is a growing field of interest, with the emergence of multiple etiologies, including infective, autoimmune, paraneoplastic, and drug‐induced causes. The field has evolved from the historical von‐Economo's encephalitis to the recent cases of parkinsonism reported after COVID‐19. Autoimmune disorders like anti‐IgLON5 and drugs like immune checkpoint inhibitors are the newer additions to this list of secondary parkinsonism. ¹ Here, we have described a patient with rapidly developing parkinsonism from Acanthamoeba encephalitis, diagnosed after diligent investigations.

Case Report

A 76‐year‐old woman presented with a history of progressive slowness, stiffness, and cognitive decline for the past 3 months. She also developed tremulousness in the upper limbs for the past 2.5 months and got admitted with a confusional state and incontinence, which developed over a week. There was no significant history of fever or headache or exposure to drug/toxin. Clinical examination revealed marked axial and bilateral appendicular rigidity and jerky tremor (postural > rest) in the upper limbs (Video 1). Brain magnetic resonance imaging (MRI) showed mild ventricular dilatation (Fig. 1). The serum autoimmune encephalitis and paraneoplastic panels were negative. Electroencephalogram (EEG) showed diffuse slowing without any epileptiform activity. Serology for HIV 1,2, HBsAg, and anti‐HCV were all negative. Cerebrospinal fluid (CSF) showed neutrophilic pleocytosis (cell count 550, 90% polymorph) with glucose 67 mg/dl (serum 100 mg/dl) and increased protein level 284 mg/dl. CSF biofire (polymerase chain reaction [PCR] for pathogens), TB GeneXpert, Venereal disease research laboratory test (VDRL), autoimmune encephalitis panel, and malignant cells were all negative. Finally, hanging drop preparation revealed motile trophozoites of free‐living amoeba (FLA) with acanthopodia morphologically, suggesting Acanthamoeba spp. (Giemsa stain +) (Fig. 2). Constantly shape‐changing character of the FLA was captured (Video 2). CSF sample was subsequently positive for Acanthamoeba spp. using PCR. A combination of rifampicin, fluconazole, and sulfamethoxazole‐trimethoprim was started. Levodopa was titrated up to 300 mg per day. In 2 weeks, the confusional state gradually improved, and tremor and rigidity decreased. Repeat CSF study showed lymphocytic pleocytosis (cell count 135, 80% lymphocytes), glucose 69 mg/dl (serum 120 mg/dl), and protein 257 mg/dl. However, the patient was subsequently lost to follow‐up.

VIDEO 1.

Axial and bilateral appendicular rigidity and jerky tremor (postural > rest) in the upper limbs.

FIG. 1.

Giemsa stain showing trophozoites of free‐living amoeba.

FIG. 2.

Brain MRI (magnetic resonance imaging) showing mild hydrocephalus in (A) T2‐FLAIR (fluid attenuated inversion recovery) and (B) T1‐contrast images.

VIDEO 2.

Hanging drop preparation showing the constantly shape‐changing character of the free‐living amoeba with acanthopodia.

Discussion

Secondary parkinsonism is a heterogeneous group of disorders comprising drug‐induced, toxin‐induced, autoimmune, paraneoplastic, vascular, traumatic, and infective etiologies. ¹ , ² Recent case reports of parkinsonism post‐COVID‐19, newly described autoimmune disorders like anti‐IgLON5, and exposure to novel chemotherapeutic agents like immune checkpoint inhibitors have drawn further attention to this field in recent times. ¹ , ³ Secondary causes of parkinsonism should always be kept as differential diagnoses as they require different therapeutic management, and most of them are refractory to conventional dopaminergic therapies.

Von Economo first described postinfective secondary parkinsonism as “encephalitis lethargica” after the 1918 flu pandemic, which has been further highlighted after the recent reports of parkinsonism post‐COVID‐19. ³ Parkinsonism has also been reported in other viral infections (Ebstein‐Barr virus (EBV), Varicella Zoster virus (VZV), Herpes Simplex virus (HSV‐1), cytomegalovirus, HIV, Coxsackie virus, dengue virus, Japanese encephalitis virus, West Nile virus), prion disease, bacterial infections (CNS Tuberculosis (CNS‐TB), neurosyphilis, mycoplasma, Whipple's disease), CNS toxoplasmosis, neurocysticercosis, and cryptococcosis. ⁴ There has been only 1 case report of rapidly developing parkinsonism and dementia secondary to amoebic encephalitis. ⁵ Similar to our patient, the CSF study in that case also initially showed neutrophilic pleocytosis and increased protein, which subsequently changed to lymphocytic pleocytosis. However, there was history of seizure, EEG changes, and striatal lesion in MRI, which were absent in our patient. Neuroinflammation, molecular mimicry to α‐synuclein, and direct insult to substantial nigra pars compacta are hypothesized as possible pathomechanisms for postinfective parkinsonism, though the exact pathogenesis of postamoebic parkinsonism is unknown. ¹ , ⁶ Associated hydrocephalus can contribute to the development of parkinsonism as well.

Amoebic meningoencephalitis can be classified into primary amoebic encephalitis, caused by Naegleria fowleri, and granulomatous amoebic encephalitis, caused by Acanthamoeba species and Balamuthia mandrillaris. ⁷ Acanthamoeba can be present ubiquitously in the air, soil, pond water, sewage, dialysis units, contaminated contact lens solutions, residential plumbing, humidifiers, and air‐conditioning units. In our patient, there was no history of bathing in ponds or sewage cleaning, 2 common sources of exposure being reported. It commonly affects immunocompromised hosts, though reports in immunocompetent hosts exist in the literature. ⁸ After entry, the amoeba spreads hematogenously to the brain, leading to inflammation of the cerebral cortex, focal granuloma, and vasculitic lesions. ⁷ CSF analysis shows increased protein with lymphocytic or neutrophilic pleocytosis. Various MRI features such as leptomeningeal enhancement, multiple ring‐enhancing lesions, cerebritis, hydrocephalus, and hemorrhagic infarcts, have been described in the literature. ⁹ Cases with Acanthamoeba encephalitis are mostly fatal due to difficulty in diagnosis, frequent misdiagnosis, and no reliably effective therapy. Varied combinations of the following drugs have been tried in the reported cases: fluconazole, ketoconazole, rifampicin, amphotericin B, sulfamethoxazole‐trimethoprim, sulfadiazine, and miltefosine. ⁸

Our patient was probably the second case reported in the literature on Acanthamoeba encephalitis presenting with rapidly progressive parkinsonism. Early diagnosis and treatment can improve the clinical and CSF scenario as seen in our case and the case previously reported by Rubio Hernandez et al. ⁵ Ventriculomegaly, CSF pleocytosis with increased protein, and negative CSF PCR for usual pathogens were the clues in this case. Hanging drop preparation of CSF should be specifically ordered in such scenarios keeping the possibility of amoebic encephalitis as an etiology for rapidly developing parkinsonism.

Author Roles

(1) Research project: A. Conception, B. Organization, C. Execution. (2) Manuscript preparation: A. Writing of the first draft, B. Review and critique.

J.G.: 1B, 1C, 2A

A.S.: 1C, 2B

S.M.: 1B, 1C

N.S.: 1B, 1C

A.K.: 1C

P.B.: 1B, 1C

H.K.: 1A, 2B

Disclosures

Ethical Compliance Statement: We confirm that the approval of an institutional review board/patient consent was not required for this work. We also confirm that the patient has given written informed consent for the publication of her video. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: The authors declare no conflicts of interest or funding relevant to this work.

Financial Disclosures for the Previous 12 Months: The authors declare that there are no additional disclosures to report.