Infection-associated dystonia: A narrative review

Rahul Yadav; Vijay Shankar; Soaham Desai

doi:10.4103/AOMD.AOMD_13_21

REVIEW ARTICLES

Year : 2021 | Volume : 4 | Issue : 3 | Page : 111-120

Infection-associated dystonia: A narrative review

Rahul Yadav¹, Vijay Shankar², Soaham Desai³
¹ Department of Neurology, Shree Krishna Hospital and Pramukhswami Medical College, Bhaikaka University, Karamsad, Anand, Gujarat, India
² Department of Neurology, Apollo Hospital, Greams Road, Chennai, India
³ Department of Neurology, Shree Krishna Hospital and Pramukhswami Medical College, Bhaikaka University, Karamsad, Anand, Gujarat, India; Department of Neurology, Apollo Hospital, Greams Road, Chennai, India

Date of Submission	06-Apr-2021
Date of Decision	28-Aug-2021
Date of Acceptance	28-Oct-2021
Date of Web Publication	22-Dec-2021

Correspondence Address:
Dr. Soaham Desai
Consultant Neurologist and Head, Department of Neurology, Shree Krishna Hospital and Pramukhswami Medical College, Bhaikaka University, Karamsad, Anand, Gujarat.
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AOMD.AOMD_13_21

Abstract

Infectious diseases are common in tropical countries, and varied complications associated with such diseases are frequently encountered. Movement disorders are a complication of infectious diseases, and the spectrum of movement disorders differs between tropical countries and other countries. We screened three electronic databases for cases of dystonia presenting as a manifestation of infections diseases and selected cases and series describing chorea associated with infections. The studies were identified and data regarding the study design, sample size, neurological assessment, and diagnostic workup, including brain imaging and cerebrospinal fluid analysis were extracted. After a detailed review of 139 selected articles, 39 articles were referred to in the final manuscript of this narrative review. Dystonia is most commonly associated with Japanese encephalitis than other central nervous system infections. The hypothesized mechanisms of infection-related dystonia are vasculopathy, space-occupying lesions, autoimmune reactions, inflammation, or via anti-dopaminergic drug therapy. The infections presenting with dystonia include tuberculosis, Japanese encephalitis, streptococcal infections, varicella-zoster virus, subacute sclerosing panencephalitis, dengue, and neurocysticercosis. In this narrative review, we discuss the different types of central nervous system infections that present with dystonia.

Keywords: Chorea, dystonia, infection, movement disorder, tuberculosis

How to cite this article:
Yadav R, Shankar V, Desai S. Infection-associated dystonia: A narrative review. Ann Mov Disord 2021;4:111-20

How to cite this URL:
Yadav R, Shankar V, Desai S. Infection-associated dystonia: A narrative review. Ann Mov Disord [serial online] 2021 [cited 2023 May 30];4:111-20. Available from: https://www.aomd.in/text.asp?2021/4/3/111/333360

Introduction

In tropical countries, infectious diseases are common and their varied manifestations are often encountered. Movement disorders (MDs) are occasionally reported to be a complication of infectious diseases, and the spectrum of MDs differs between tropical and other countries. Dystonia is a hyperkinetic MD characterized by involuntary, patterned, sustained, or intermittent contractions of opposing muscles causing repetitive twisting movements or abnormal posture, or both. Dystonia is the most commonly reported post-infectious MD, according to a study on movement disorders due to infectious diseases. In that study, pure dystonia was observed in 28.6% patients and dystonia with choreoathetosis was observed in 22.9% patients. Thus, 51.5% of the patients with post-infectious MDs had overall dystonia.^[1] The common organisms responsible for dystonia are listed below:

Bacteria: Mycobacterium tuberculosis, Streptococcus, Mycoplasma, Neurosyphilis, Tropheryma whipplei

Virus: Japanese encephalitis (JE), human immunodeficiency virus (HIV), subacute sclerosing panencephalitis (SSPE), varicella-zoster virus (VZV), coronavirus Disease 2019 (COVID-19)

Parasites: Malaria, neurocysticercosis, toxoplasma

Prion disease

Here, we review the current literature on dystonia associated with these infections.

Methodology

A literature search was independently conducted by two reviewers who reviewed all cases of dystonia in patients with proven CNS infections. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and used three comprehensive electronic medical literature databases, PubMed, Embase, and Google scholar, to search for articles on infection-associated dystonia starting from Jan 1, 1985. The search strategy was developed using a combination of Medical Subject Heading terms and keywords. The search strings were as follows: dystonia, infection, virus, encephalitis, tuberculosis, streptococcus, mycoplasma, JE, SSPE, HIV, acquired immunodeficiency syndrome (AIDS), VZV, dengue, COVID-19, Creutzfeldt-Jakob disease ^{More Details} (CJD), neurocysticercosis, and Whipple disease. In addition, we hand searched the reference lists of all identified articles in the electronic search using common search engines (e.g., Google) to include studies or reports not identified by the search. Ethical approval was not required for this study. The search yielded studies reporting dystonia among patients with different CNS infections ([Figure 1]). Data was extracted regarding study design, sample size, neurological assessment, and diagnostic workup, including brain imaging and CSF analysis. After detailed review of 139 selected articles and after excluding articles in non-English languages and with incomplete details or contentious or analogous descriptions, a total of 39 articles were referred to in the final manuscript. We separately discuss each of the infections in this narrative review and summarize the salient features in [Table 1].

Figure 1: PRISMA flowchart of the selection of articles for the narrative review

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Table 1: Summary of the infection related to dystonia

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Bacterial infections and dystonia

Mycobacterium tuberculosis

The WHO factsheet revealed that six countries accounted for 60% of tuberculosis (TB) patients worldwide, and the highest incidence was from India, followed by other countries.^[2] In a study by Alarcón et al.,^[3] 30 out of 180 patients with CNS TB were found to develop MD. Among the 30 patients, 20 had tremor, seven had chorea, and three had dystonia. Patients with chorea and dystonia had a more severe disease. Another study by Alarcón et al.^[4] on MDs secondary to intracranial tuberculoma reported that 16 out of 49 patients had MDs. Dystonia was reported in three patients, and they had a more severe disease that was associated with significant motor impairment. Among studies involving CNS TB, dystonia is commonly produced by tuberculomas in the basal ganglia, thalamus, and cerebellar region; CNS TB with dystonia suggests a more severe disease.^[5]

Paroxysmal autonomic instability with dystonia is generally reported in patients with traumatic brain injury, intracerebral hemorrhage, or brain tumor. It has also been reported in patients with CNS infections. One case of paroxysmal autonomic instability with dystonia was reported in a patient with CNS and pulmonary TB. The patient developed hypertension, sinus tachycardia, fever, tachypnea, decreased oxygen saturation, and dystonia. Magnetic resonance imaging (MRI) of the patient showed abnormal signal intensity lesions in the hippocampus, thalamus, and anterior parts of the lentiform nucleus and caudate nucleus.^[6]

Streptococcal infection

Sydenhamoccal infectionstability with dystonia is generally reported in patients with traumatic brain injury, intracerebral hemorrhagoccal dystonia has also been reported. Kendi et al.^[7] reported the case of a 7-year-old boy presenting with rigidity and breathing difficulty due to streptococcal pharyngitis. He subsequently developed dystonia 2 days later and was treated with dexamethasone. Laboratory reports showed high titers of antistreptolysin O and antideoxyribonuclease antibody. MRI showed hyperintensities on T2-weighted imaging (T2WI) in the bilateral head of caudate and putamen. His neurological symptoms and the extent of T2 hyperintensity improved after 12 months of follow-up. The MRI spectroscopy findings of this patient supported the hypothesis that the mechanism of the basal ganglia lesion, resulting in dystonia in poststreptococcal infections, could be due to an antibody-mediated autoimmune reaction. Dale et al.^[8] reported two patients with postpharyngitis dystonia. The serological tests of both patients were suggestive of recent beta hemolytic streptococcal infection. Both patients were positive for antibasal ganglia antibodies. Bilateral caudate and putaminal hyperintensities were observed in the first patient and bilateral caudate with right putaminal hyperintensities on T2WI was observed in the second patient. Dale et al.^[9] reported another patient with poststreptococcal pharyngitis who presented with paroxysmal dystonic choreoathetosis. Thus, streptococcal infections may rarely be associated with dystonia, which may hypothetically be due to a para-infectious autoimmune mechanism.

Mycoplasma pneumoniae

M. pneumoniae commonly affects the pulmonary system, while CNS is affected in only approximately 2–7% cases. Kim et al.^[10] reported the case of a 7-year-old boy who developed features of Parkinsonism ^{More Details} and dystonia. MRI showed hyperintensities on T2WI in the bilateral basal ganglia region. Serial serological tests were suggestive of M. pneumoniae infection. The patient 7-year-old boy who developed features of parkins^[10] Another case report described an 8-year-old boy presenting with persistent dystonia with bilateral striatal necrosis secondary to M. pneumoniae-associated respiratory infection.^[11] Few case reports of M. pneumoniae infection resulting in bilateral striatal necrosis are also reported. In one study, the mechanism of striatal necrosis due to M. pneumoniae infection was related to a significant increase in interleukins 6 and 8 in serum and CSF. An increase in these cytokines may cause microvascular injury and may lead to local vascular occlusion-related injury, leading to basal ganglia necrosis, which, in turn, results in dystonia along with other neurological manifestations.^[12]

Whipple disease

Whipple disease is a rare but treatable infectious disease caused by T. whipplei. The common manifestations of MDs are oculomasticatory myorhythmia, myoclonus, ataxia, and gait and balance impairment. Dystonia was reported in six patients, of which four had isolated blepharospasm. Parkinsonism, tremor, dystonia, chorea, and bruxism were rarely reported (<10% of patients).^[13]

Viral infections and dystonia

Japanese Encephalitis (JE)

JE is a zoonotic disease caused by a JE virus-infected mosquito bite. Parkinsonism and dystonia are common MDs associated with JE. Misra and Kalita^[14] reported that 67.6% patients with JE had MDs. In another study^[15] patients with JE who developed MDs were divided into two groups: group-1 comprised patients with parkinsonism and group-2 comprised patients with parkinsonism combined with additional dystonia or dyskinesia. There were 16 patients in group-1 and 19 in group-2. They observed that parkinsonism was more pronounced in group-2 and the patients had poor recovery. In their study, brain imaging revealed that the thalamus was the most frequently involved region, followed by the basal ganglia and the midbrain. Kalita and Misra^[16] described five patients with markedly severe dystonia among 50 JE patients. These patients developed grade 4 retrocollis, opisthotonos, and limb dystonia 1–3 weeks after JE. Other features were jaw-opening dystonia in three patients and jaw clenching in one. Rigidity and fixed dystonia were also noted in some patients. Radiological features of all five patients showed bilateral thalamic involvement, three showed brainstem involvement, and two showed basal ganglia involvement along with the bilateral thalamus.^[16] Another study showed two children with severe generalized dystonia, and brain MRI revealed bilateral thalamic lesions. Viral antibodies and antigens were absent in the CSF of all patients. In addition, generalized dystonia associated with basal ganglia lesions in JE was reported in one patient, in a series assessing MDs in patients with JE from Northeast India. In that series, tremor, rigidity, and bradykinesia were common after JE infection.^[17]

Human Immunodeficiency Virus (HIV)

MDs have been reported in approximately 2–3% of patients with HIV infection. MDs are usually present along with peripheral neuropathy, myelopathy, seizures, or dementia. MDs in HIV are usually related to opportunistic infections; they may be directly caused by HIV or due to antidopaminergic drug therapy. In a large study conducted in 2460 HIV patients, neurological manifestations were observed in 42.8% patients, and 28 (2.7%) had MDs. The common MDs were parkinsonism in 14 (50%), hemichorea in six (21.4%), myoclonus in four (14.2%), painful legs and moving toes in two (7.2%), Holmes tremor in one (3.6%), and hemidystonia in one (3.6%). Hemidystonia was reported in a young male with toxoplasmosis in the contralateral basal ganglia region. He was treated with sulfadiazine and pyrimethamine, which resulted in improvement in the lesions on radiological assessment without improving dystonia.^[18] In one study, dystonia was reported in four patients with AIDS. Dystonia in two of these patients was due to progressive multifocal leukoencephalopathy, and imaging showed lesions in the frontal and parietal white matter. Among them, one had left arm dystonia and the other had bilateral upper limb dystonia. The third patient developed hemidystonia associated with cervical dystonia. He was diagnosed with toxoplasmosis (biopsy proven) in the thalamus. The fourth patient had AIDS–dementia complex and developed cervical dystonia following risperidone therapy.^[19] Vielhauer et al.^[20] reported an HIV patient with cytomegalovirus infection. The patient presented with spasmodic torticollis and extrapyramidal symptoms. He was found to have bilateral internal jugular vein thrombosis. His torticollis resolved following anticoagulation therapy, and other extrapyramidal symptoms resolved with anticytomegalovirus therapy.

Thus, it can be observed that MDs with HIV usually occur as secondary infections (most commonly toxoplasmosis). However, MDs with HIV can occur as a result of drugs or direct and indirect effects of HIV. Management of MDs in HIV patients includes symptomatic treatment of MD, highly active antiretroviral therapy, and treatment of opportunistic infections.

Varicella Zoster Virus (VZV)

The neurological manifestations of VZV are encephalitis, meningitis, vasculopathy-related infarction, myelitis, and cranial nerve palsies. Patients with encephalitis and vasculopathy may present with MDs. CNS complications with VZV include acute cerebellar ataxia, stroke, acute disseminated encephalomyelitis (ADEM), meningitis, and bilateral striatal lesions. A 17-year-old girl developed lingual and oromandibular dystonia 5 days after skin eruptions. The dystonia initially persisted for 4 hours and recurred after 12 hours, resulting in jaw dislocation.^[21] Dystonia, accompanied by bilateral striatal lesions, has been reported in three patients with VZV infection.^[22] Bilateral striatal lesions can present with features of encephalopathy and pyramidal or extrapyramidal symptoms.^[23] After VZV infection, cerebral arteriopathy may result in ischemic stroke involving the basal ganglia leading to hemiparesis and hemidystonia.^[24] Furthermore, dystonia may rarely occur as a delayed presentation of post-VZV vasculitis/angiopathy, leading to stroke, involving the basal ganglia. Delayed occurrence of dystonia after almost 3 months of VZV infection was reported in an immunocompetent elderly man who initially presented with incomplete Brown–Séquard syndrome secondary to VZV myelitis. After 3 months of initial presentation, he had basal ganglia bleed due to angiopathy and presented with dystonia involving his lower limbs. He was treated with valacyclovir and methylprednisolone again, which resulted in complete cessation of symptoms, with a marked resolution of the lesion on MRI.^[25]

Subacute Sclerosing Panencephalitis

Subacute sclerosing panencephalitis is a slowly progressive CNS inflammatory disease caused by the measles virus. Goswami and Roy^[26] reported the case of an 8-year-old unimmunized girl who presented with dystonia of the right-sided limbs with cognitive decline. Her brain MRI showed hyperintensities involving the bilateral occipital lobes and left globus pallidus. She was diagnosed with SSPE based on highly elevated CSF and serum antimeasles immunoglobulin (Ig) G titers. Dystonia partially responded to trihexyphenidyl, benzodiazepines, and carbamazepine. In addition, Kannan et al.^[27] reported the case of an 8-year-old boy with SSPE presenting as rapid-onset dystonia parkinsonism, who subsequently developed myoclonus and cognitive decline secondary to SSPE.^[27] In general, SSPE presents with myoclonus, parkinsonism, and cognitive decline; however, in atypical cases, it may present with dystonia. Neuroimaging features in SSPE are non-specific, and management is performed by symptomatic treatment for dystonia and myoclonus.

Dengue

Dengue is one of the most common viral infections encountered in tropical countries. It is caused by an RNA virus belonging to the family Flaviviridae and is spread by Aedes mosquitoes. There are four serotypes (DENV-1, −2, −3, and−4) that can cause dengue fever. The nervous system complications with dengue include encephalitis, meningitis, stroke, cerebellar syndrome, transverse myelitis, ADEM, Guillain–Barré syndrome, myositis, hypokalemic periodic paralysis, MD-like dystonia, tremor, and parkinsonism.^[28] Mishra and Pandey^[29] reported the case of an 18-year-old woman presenting with headache, fever, altered sensorium, generalized dystonia, and parkinsonism for 1 month. On evaluation, CSF analysis showed lymphocytic pleocytosis with elevated protein and normal sugar levels. She was diagnosed with dengue encephalitis because of positive IgG antibodies in CSF. Her brain MRI revealed the characteristic double doughnut sign observed in dengue encephalitis. She had mild improvement after 15 days of treatment with levocarbidopa and trihexyphenidyl.^[29] Similarly, an 11-year-old girl presented with fever for 5 days and altered sensorium for 2 days. CSF analysis showed lymphocytic pleocytosis with elevated protein and normal sugar levels. Serum IgG/IgM antibodies and CSF polymerase chain reaction for the dengue virus were positive. Brain MRI revealed hemorrhage in the thalami and pons. She developed hemiparesis, dystonia, and tremor, which improved after 3 months.^[30]

COVID-19

The coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus termed “severe acute respiratory syndrome coronavirus-2.” The clinical manifestations of COVID 19 are fever, nonproductive cough, sore throat, breathing difficulty along with abdominal pain, diarrhea, and conjunctivitis. Neurological manifestations are observed in approximately 36 coronavirus termed “severe acute respiratory syndrome coronavirus-2.” The clinical manifestations of COVID 19 are fever, nonproductive cough, sorKenniff et al.^[31] described two middle-aged women who developed myoclonus and dystonia 3–4 weeks after COVID-19 lung infection, which they termed as COVID-associated myoclonus and dystonia syndrome. This syndrome is considered to be an immune para-infectious/post-infectious condition.

Parasitic infection and dystonia

Neurocysticercosis

Neurocysticercosis (NCC) is a parasitic infection caused by Taenia solium. The clinical manifestations depend on the location, number, and stage of the cysts in CNS. The most common CNS manifestations are chronic headache, seizures, focal neurological deficits, raised intracerebral pressure, and cognitive decline. In a study of 590 patients in Ecuador, two patients developed dystonia with cystic lesions in the putamen.^[32] Thirteen patients with dystonia were described in association with NCC, in a systematic review by Rissardo et al.^[33] The most common MDs are focal (blepharospasm, cervical, scalp, and writer’s cramp), segmental (Meige syndrome), and hemidystonia. Other common MDs associated with NCC are parkinsonism, ataxia, chorea, dystonia, tremor, myokymia, myoclonus, ballism, and tics.

Malaria

Cerebral malaria is a severe neurological complication caused by Plasmodium falciparum infection. In malaria, adherence and sequestration of red blood cells in the cerebral microvasculature results in endothelial damage, blood–brain barrier dysfunction, cerebral edema, and raised intracerebral pressure. The sequestration leads to occlusion of the microvasculature and may cause hypoxic brain injury. The most common manifestation of cerebral malaria is impaired consciousness. In addition, it may cause focal neurological deficits; seizures; and MDs including ataxia, tremor, and dystonia.^[34] In a study conducted by Idro et al.^[35] in Uganda, 23 patients with cerebral malaria were studied. The most common impairments were motor deficits in 14 patients, speech problems in 14 patients, hearing problems in nine patients, behavioral problems in 11 patients, epilepsy in 12 patients, visual complaints in 12 patients, and cognitive impairment in nine patients. Six out of 14 patients with motor deficits had movement and gait disorders, including ataxia, choreoathetosis, dystonia, and poor neck control.

Prion disease

Creutzfeldt–Jakob Disease (CJD)

CJD is a rare neurodegenerative disease that causes rapidly progressing dementia, myoclonus, ataxia, visual disturbance, extrapyramidal, and pyramidal abnormalities. CJD is classified as a transmissible spongiform encephalopathy. Approximately, 85% of CJD occurs as a sporadic disease, and as much as 15% patients develop CJD due to inherited mutations of the prion protein gene. Cohen et al.^[36] described 15 patients with dystonia during the course of CJD. Dystonia is one of the most common MDs that can occur in 45% of CJD patients. It presents as focal dystonia involving the upper limb or neck, segmental dystonia involving the trunk and shoulders, hemidystonia, and blepharospasm with hand dystonia. Generalized dystonia usually occurs in the later stages of the disease, or a focal or hemidystonia can evolve into generalized dystonia.^[37] Other common MDs associated with CJD are myoclonus, myoclonus dystonia, choreoathetosis, tremor, hemiballismus, and atypical parkinsonian syndromes. A typical cortical ribboning pattern associated with the presence of the 14-3-3 protein in CSF and/or a typical electroencephalogram pattern confirms CJD. There is no curative treatment for CJD, and it is symptomatically treated.

Pathophysiology of infection-associated dystonia

There are various suggested mechanisms of infection-related dystonia, such as the direct or indirect neurotropic effect of viruses, space-occupying lesions, opportunistic infections, neuroinflammation, vasculitis, autophagy, synaptic dysfunction, and drugs used to treat the infections. Dystonia can occur secondary to the disruption of the striato-pallidal complex or its connections, the mesencephalon, and the thalamus.^{[1],[2],[3],[14],[17]} The involvement of the basal ganglia and its dysfunction are important factors in the pathogenesis of dystonia. In the context of infections, dystonia can occur suddenly, in an acute manner with onset of an infection, or it may appear in a subacute manner or as a chronic sequelae/complication of an infection. Acute dystonia can occur as a result of vascular insult (vasculitis associated with infection) or cytotoxic/vasogenic edema in the brain, as is observed with tuberculous meningitis (TBM).^[2] Acute dystonia occurring a few weeks after an infection would generally be a result of para-infectious/post-infectious immune-mediated reaction due to molecular mimicry, as observed in dystonia with poststreptococcal or postmycoplasma infections.^{[7],[8],[9],[10],[11]} Subacute dystonia would occur due to structural brain injury, especially in the basal ganglia region and its network connections by direct injury due to granuloma formation and edema, as observed with granulomatous infections like tuberculoma, neurocysticercosis, and toxoplasmosis, in the setting of HIV infection^[18],[19] ([Figure 2] and [Figure 3]). Chronic, persistent dystonia post-infection generally occurs as a result of gliosis secondary to brain injury, as observed with TBM or JE ([Figure 3], Videos 1 and 2). In addition, transient dystonic reactions to drugs used for symptomatic management of infections may occasionally be observed (e.g., metoclopramide-associated oromandibular dystonia or oculogyric crisis); these have not been included in this review, since they are not a direct result of infections.

Figure 2: Brain magnetic resonance imaging (MRI) in different patients with different infections of the brain A, B: calcified granuloma involving the pons, suggestive of neurocysticercosis; C, D: bilateral thalamic T2 hyperintense signals in a patient with Japanese encephalitis. The patient’s video depicting chronic persistent dystonia is shown in Video 1 E, H: multiple contrast-enhanced lesions involving the thalamus, mid brain, and left parietal lobe in a patient with HIV–AIDS, with positive antitoxoplasma IgM and IgG antibody, suggestive of CNS toxoplasmosis; I–L: brain MRI of a patient with Creutzfeldt–Jakob Disease showing bilateral asymmetrical pulvinar as well as bilateral cerebral cortical gyral hyperintense signals

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Figure 3: Head contrast-enhanced computed tomography (CECT) and chest X-Ray of a patient with central nervous system and pulmonary tuberculosis associated with focal dystonia of the left hand, as depicted in Video 2. The patientnced computed tomography (CECT) and chest X-Ray of a patient with central nervous system and pulmonary tuberculosis associated with focal dystonia of the left hand, as depicted in CNS toxoplasmosis; I–L: brain MRtomeningeal enhancement postcontrast with the right fronto-parietal hypodense lesion in the right middle cerebral artery territory, with partial enhancement, indicating subacute infarct; this indicates vasculitis in a case of chronic meningitis secondary to tuberculosis

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Treatment

To effectively diagnose the underlying infection ([Figure 4]) and improve the associated dystonia, a high index of suspicion and a combination of early treatment and symptomatic therapy is essential. Early initiation of disease-specific therapy for underlying infections will help in improving favorable long-term outcomes. Several medications, including anticholinergic medications, dopaminergic agents, dopamine-blocking and -depleting agents, baclofen, and benzodiazepines, are available for the symptomatic management of dystonia. The first choice of medication as therapy is anticholinergic medications and benzodiazepines.^[38] Given the rarity of infection-associated dystonia, the evidence for the efficacy of a given medication is limited. Botulinum toxin is most useful for focal, cranial, or cervical dystonia. It may also help control the most disabling symptom of segmental or generalized dystonia.^[38] Intrathecal baclofen infusion may be beneficial when spasticity coexists with dystonia. The globus pallidus internus is a target for deep brain stimulation, and this with pallidotomy is useful in primary generalized, segmental, and focal dystonia; however, it is less effective in secondary dystonia due to infections.^[39]

Figure 4: Flowchart of the approach to a patient with dystonia and fever

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Limitations

This narrative review is based on the information available from case reports and case studies in the literature. All the limitations of a narrative review are applicable to this review. Furthermore, associated clinical features of interest like comorbid non-neurologic conditions, associated neurologic symptoms like cognitive deficiencies associated with dystonia, quality of life, or long-term disability assessment could not be assessed with specific infections because of nonspecific objective measures, subgroup selection, and evaluation bias in the reviewed published articles. Some studies could not be included due to insufficient information. In view of the rarity of some of the diseases and the fact that only some case series and case reports are reported, it was difficult to ascertain the exact incidence and prevalence of these disorders to any particular region. In our attempt to review this rare group of dystonia associated with infections, these limitations point to the need to set up dedicated registries for infection-associated MDs, including dystonia, worldwide. A recently formed study group on infection-related MDs by the International Parkinson and Movement Disorder Society is one such initiative that would help us gain further knowledge and understanding into the prevalence, clinical profile, natural history, prognosis, and regional differences in the different forms of infection-related dystonia and other MDs.^[40]

Conclusions

Dystonia is most commonly associated with JE than other CNS infections in tropical countries. The basal ganglia, thalamus, and cerebellum are the common sites of lesions, resulting in dystonia. The hypothesized mechanisms of infection-related dystonia are vasculopathy, space-occupying lesions, autoimmune reactions, inflammation, or via antidopaminergic drug therapy. In most patients, dystonia is associated with other neurological manifestations, and usually, dystonia in patients with infections suggests a more severe disease.

Acknowledgement

None.

Author contributions

Research project: A. Conception, B. Organization, C. Execution

Statistical analysis: A. Design, B. Execution, C. Review and Critique

Manuscript preparation: A. Writing of the first draft, B. Review and Critique

RY: 1B, 1C, 3A; VS: 1A, 1B, 2B, 2C, 3B; SD: 1A, 1B, 1C, 2A, 2B, 2C, 3B

Ethical compliance statement

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.

Conflict of interest

There are no conflicts of interest to declare.

Financial disclosures

None.

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