Figure 1
Contrast-enhanced brain MRI in an HIV-positive patient with cerebral toxoplasmosis.
Figure 2
Cerebral toxoplasmosis in an HIV-positive adult — MRI and proton MR spectroscopy. Localized ^1H-MRS acquired from the boxed region demonstrates a prominent lipid–lactate complex with globally reduced metabolites, including decreased N-acetyl aspartate and low choline. The spectral pattern—lipid–lactate prominence without amino-acid peaks. MRS features suggest a necrotizing opportunistic infection and, in the context of HIV, is characteristic of toxoplasmic abscess.
Video 1
Video of an HIV-positive patient with cerebral toxoplasmosis showing right-sided hemichorea, predominantly involving the lower limb.
Figure 3
PRISMA flow diagram showing the process of study identification, screening, eligibility assessment, and final inclusion.
Table 1
Comparative Clinical, Demographic, Neuroimaging, and Outcome Characteristics of Hyperkinetic, Hypokinetic, and Cerebellar Movement Disorders in Central Nervous System Toxoplasmosis (Summary of Supplementary table 1–3).
| VARIABLE | HYPERKINETIC MOVEMENT DISORDERS (N: 42) | HYPOKINETIC MOVEMENT DISORDERS (N: 9) | ATAXIA AND OTHER CEREBELLAR SYNDROMES (N: 9) |
|---|---|---|---|
| Age (in years) | Mean: 38.7 Median: 36.5 Mode: 35 Range: 11–78 IQR: 11 | Mean: 52.9 Median: 56 Range: 31–66 IQR: 16 NA: 1 | Mean: 45.1 Median: 50 Mode: 53 Range: 23–60 IQR: 18.5 |
| Sex | Male (M): 33 (78.6%) Female (F): 9 (21.4%) | Male: 5 (55.6%) Female: 4 (44.4%) | Female (F): 4 (44.4%) Male (M): 5 (55.6%) |
| Geographic distribution of published reports | Total: 33 Africa: 2 (6.1%) Asia: 3 (9.1%) Europe: 8 (24.2%) North America: 12 (36.4%) South America: 8 (24.2%) | Total: 9 Asia: 2 (22.2%) Europe: 4 (44.4%) North America: 3 (33.3%) | Total: 9 Asia – 4 (44.4%) Europe – 3 (33.3%) North America – 2 (22.2%) |
| Immune status | HIV-related immunosuppression: 37 (88.1%) Non-HIV immunocompromised: 1 (2.4%) Immunocompetent: 4 (9.5%) | HIV-positive (including all with AIDS stage, ART, well-controlled, confirmed by tests): 7 (77.8%) Immunocompetent (HIV-negative): 1 (11.1%) Other immunocompromised (non-HIV): 1 (11.1%) | HIV-positive/AIDS: 6 (66.7%) Other immunocompromised (non-HIV): 1 (11.1%) Immunocompetent: 2 (22.2%) |
| CD4 count | <50 cells/µL: 12 (28.6%) 50–99 cells/µL: 6 (14.3%) 100–199 cells/µL: 3 (7.1%) ≥200 cells/µL: 2 (4.8%) Other specified values: 2 (4.8%) Not applicable/not reported: 17 (40.5%) | <50 cells/µL: 2 (22.2%) 100–199 cells/µL: 2 (22.2%) ≥200 cells/µL: 3 (33.3%) Not applicable/not reported: 2 (22.2%) | <50 cells/µL: 2 (22.2%) 50–99 cells/µL: 1 (11.1%) 100–199 cells/µL: 1 (11.1%) Not applicable/not reported: 5 (55.6%) |
| Duration of illness | <2 weeks: 8 (21.1%) 2 weeks–<3 months: 13 (34.2%) ≥3 months: 10 (26.3%) Not specified/unknown: 7 (18.4%) | <2 weeks: 2 (22.2%) 2 weeks–<3 months: 2 (22.2%) ≥3 months: 5 (55.6%) | <2 weeks: 4 (44.4%) 2 weeks–<3 months: 4 (44.4%) ≥3 months: 1 (11.1%) |
| Likely Mode of Infection | Reactivation of latent toxoplasmosis: 17 (40.5%) Oral ingestion of oocysts: 3 (7.1%) Vertical transmission: 1 (2.4%) Blood transfusion: 1 (2.4%) Unknown/not specified: 20 (47.6%) | Reactivation of latent toxoplasmosis: 5 (55.6%) Hematogenous dissemination: 1 (11.1%) Intravenous drug use: 1 (11.1%) Blood transfusion: 1 (11.1%) Unknown/not specified: 1 (11.1%) | Reactivation/likely reactivation: 8 (88.9%) Acquired (new infection): 1 (11.1%) |
| Diagnostic Method for Toxoplasmosis | Serology + Neuroimaging: 19 (45.2%) Serology + Neuroimaging + Clinical response: 6 (14.3%) PCR-based: 4 (9.5%) Histopathology/Autopsy: 3 (7.1%) Neuroimaging only: 1 (2.4%) Other/mixed methods: 9 (21.4%) | MRI ± serology (without DaTSCAN): 3 (33.3%) DaTSCAN (with MRI + serology): 1 (11.1%) Molecular/serological confirmation (PCR or high IgG titers): 3 (33.3%) Histopathology/biopsy confirmation: 1 (11.1%) Presumed (epidemiologic evidence only): 1 (11.1%) | Serology + Neuroimaging: 3 (33.3%) Serology + Neuroimaging + Histopathology: 2 (22.2%) PCR-based (CSF/blood/tissue): 2 (22.2%) Histopathology only (with or without serology): 1 (11.1%) Other/specialized tests (e.g., Sabin-Feldman dye test, mouse inoculation): 1 (11.1%) |
| CNS Involvement Pattern | Basal ganglia involvement: 18 (47.4%) Thalamic involvement: 14 (36.8%) Midbrain/brainstem involvement: 8 (21.1%) Cortical involvement: 8 (21.1%) Cerebellar involvement: 3 (7.9%) Diffuse/widespread: 2 (5.3%) White matter involvement: 2 (5.3%) Subthalamic nucleus involvement: 2 (5.3%) Normal neuroimaging: 1 (2.6%) | Basal ganglia involvement (with or without other regions): 6 (66.7%) Thalamic involvement (with or without other regions): 2 (22.2%) Midbrain/brainstem involvement: 2 (22.2%) Cortical involvement (frontal, parietal, occipital, temporo-occipital): 3 (33.3%) Diffuse/widespread involvement: 1 (11.1%) White matter involvement: 1 (11.1%) | Cerebellar involvement (with or without other regions): 9 (100%) Brainstem involvement: 2 (22.2%) Thalamic involvement: 1 (11.1%) Cerebral hemispheres involvement: 2 (22.2%) Spinal cord/nerve root involvement: 1 (11.1%) Leptomeningeal involvement: 1 (11.1%) |
| Dominant movement disorders present | Hemichorea/Hemiballismus/Hemichorea-hemiballismus/Hemichoreoathetosis/Choreoballism: 20 (47.6%) Holmes tremor/Rubral tremor: 7 (16.7%) Chorea (generalized/focal): 5 (11.9%) Myoclonus: 2 (4.8%) Dyskinesia: 1 (2.4%) Tic disorder: 1 (2.4%) Akathisia: 1 (2.4%) Mixed chorea + dystonia + parkinsonism: 1 (2.4%) Dystonia (segmental/hemidystonia/focal): 3 (7.1%) Other types of tremor (non-Holmes): 1 (2.4%) | Hemiparkinsonism: 3 (33.3%) Bilateral parkinsonism: 4 (44.4%) Mixed/extrapyramidal + other features: 1 (11.1%) Subacute parkinsonism: 1 (11.1%) | Ataxia (with or without other cerebellar signs): 9 (100%) Dysarthria: 3 (33.3%) Nystagmus: 2 (22.2%) Gait disturbance/wide-based gait: 2 (22.2%) Dysmetria/incoordination: 2 (22.2%) Intention tremor: 1 (11.1%) |
| Onset relative to toxoplasmosis | At initial presentation/concurrent with diagnosis: 15 (35.7%) Delayed onset (weeks–months): 12 (28.6%) Long-term onset (≥1 year): 5 (11.9%) During disease progression/relapse/advanced stage: 6 (14.3%) Treatment-related/iatrogenic (new group): 2 (4.8%) Not clearly specified: 2 (4.8%) | At initial presentation/concurrent with diagnosis: 2 (22.2%) Delayed onset (weeks to months after diagnosis/treatment): 4 (44.4%) Long-term onset (≥1 year after diagnosis): 3 (33.3%) | At initial presentation/concurrent with diagnosis: 6 (66.7%) Delayed onset (weeks to months after diagnosis/treatment): 2 (22.2%) During disease progression/advanced stage: 1 (11.1%) |
| Duration of movement disorder/Ataxia | <2 weeks: 7 (16.7%) 2 weeks–<3 months: 16 (38.1%) ≥3 months–<1 year: 6 (14.3%) Long-term/persistent (≥1 year or until death): 13 (31.0%) | 2 weeks–<3 months: 0 (0%) ≥3 months–<1 year: 4 (44.4%) Long-term/persistent (≥1 year or until death): 5 (55.6%) | ≥3 months–<1 year: 4 (44.4%) Long-term/persistent (≥1 year or until death): 5 (55.6%) |
| Other neurological features | Motor deficits: 19 (50%) Cognitive/behavioral changes: 15 (35.7%) Speech disorders: 9 (21.4%) Cranial nerve palsies: 4 (9.5%) Visual disturbances: 3 (7.1%) Seizures: 3 (7.1%) Cerebellar signs: 3 (7.1%) Signs of raised intracranial pressure: 3 (7.1%) No additional neurological findings: 3 (7.1%) Systemic/secondary (new group): 2 (4.8%) | Cognitive impairment/decline: 4 (44.4%) Motor deficits: 3 (33.3%) Behavioral/psychiatric changes: 2 (22.2%) Cranial nerve involvement: 2 (22.2%) Other neurological signs: 3 (33.3%) | Headache-related: 4 (44.4%) Cranial nerve palsy: 1 (11.1%) Motor weakness: 2 (22.2%) Consciousness/cognitive impairment: 3 (33.3%) Peripheral nerve signs: 3 (33.3%) Other focal signs: 1 (11.1%) |
| Neuroimaging features | Ring-enhancing/granulomatous lesions: 31 (73.8%) Non-enhancing hyperintense/hypointense lesions: 4 (9.5%) Diffuse atrophy/edema (non-focal): 3 (7.1%) Normal imaging: 2 (4.8%) Unspecified/Other CT-MRI: 2 (4.8%) | Ring-enhancing lesions (including abscesses) on MRI/CT: 4 (44.4%) Gliosis/encephalomalacia: 2 (22.2%) White matter changes/atrophy: 1 (11.1%) Characteristic/atypical (“bullseye”) lesions: 1 (11.1%) Small enhancing internal capsule lesions: 1 (11.1%) | Cerebellar involvement: 3 (33.3%) Thalamic/cerebellitis/muscle involvement: 1 (11.1%) Basal ganglia ± multiple sites: 1 (11.1%) Cerebral hemispheres ± herniation: 1 (11.1%) Post-operative change/progression: 1 (11.1%) Normal imaging: 1 (11.1%) |
| Lesion Location | (multiple sites possible per patient) Basal ganglia: 23 (54.8%) Thalamus: 18 (42.9%) Subthalamic nucleus: 10 (23.8%) Midbrain/brainstem: 9 (21.4%) Frontal lobe: 9 (21.4%) Parietal lobe: 5 (11.9%) Occipital lobe: 4 (9.5%) Temporal lobe: 3 (7.1%) Cerebellum: 3 (7.1%) White matter: 3 (7.1%) Normal/no lesion: 2 (4.8%) Diffuse/meningitis-related: 1 (2.4%) | Basal ganglia: 8 (88.9%) Thalamus: 3 (33.3%) Midbrain/brainstem: 1 (11.1%) Frontal lobe: 2 (22.2%) Parietal lobe: 1 (11.1%) White matter involvement: 3 (33.3%) Corpus callosum: 1 (11.1%) | Cerebellum only: 3 (33.3%) Cerebellum + other CNS sites: 4 (44.4%) Non-cerebellar CNS sites only: 1 (11.1%) Muscle ± spinal: 1 (11.1%) |
| Treatment | Standard anti-toxoplasma regimen (pyrimethamine + sulfadiazine ± folinic acid/leucovorin ± steroids): 25 (59.5%) Alternative regimens (TMP-SMX, clindamycin, spiramycin, other sulfa drugs, pyrimethamine monotherapy): 10 (23.8%) Empirical/unspecified therapy: 2 (4.8%) No treatment/not applicable: 5 (11.9%) | Pyrimethamine + sulfadiazine (with or without folinic acid): 3 (33.3%) Pyrimethamine + other agents (clindamycin, TMP-SMX, corticosteroids): 3 (33.3%) Trimethoprim-sulfamethoxazole (TMP-SMX) + ART/HAART: 1 (11.1%) No treatment given/diagnosis post-mortem: 1 (11.1%) Not reported: 1 (11.1%) | Pyrimethamine + sulfadiazine ± folinic acid/leucovorin ± ART ± corticosteroids: 4 (44.4%) Pyrimethamine + sulfadiazine (induction) + corticosteroids + mycophenolate mofetil: 1 (11.1%) Clindamycin-based regimen (± pyrimethamine, azithromycin, pyridoxine): 2 (22.2%) IV cotrimoxazole (± corticosteroids, ART): 1 (11.1%) No specific anti-Toxoplasma therapy (empirical antibiotics only): 1 (11.1%) |
| Duration of Treatment | <1 month: 4 (9.5%) 1 month–<3 months: 9 (21.4%) ≥3 months–<1 year: 5 (11.9%) ≥1 year/long-term: 3 (7.1%) Not specified/not stated: 19 (45.2%) Mixed/multiple-course therapy: 2 (4.8%) | <2 months: 3 (33.3%) 2–<6 months: 2 (22.2%) ≥6 months: 1 (11.1%) Not specified/not applicable: 3 (33.3%) | < 2 weeks: 3 (33.3%) 2–8 weeks: 3 (33.3%) > 8 weeks/multiple courses: 2 (22.2%) Not applicable: 1 (11.1%) |
| Symptomatic Therapy for movement disorders | Neuroleptics (haloperidol, risperidone, thioridazine, olanzapine, quetiapine, aripiprazole): 14 (33.3%) VMAT inhibitors (tetrabenazine): 3 (7.1%) Benzodiazepines (clonazepam, diazepam, delorazepam): 9 (21.4%) Dopaminergic/Parkinsonian drugs (levodopa, amantadine, propranolol): 6 (14.3%) Anticonvulsants (valproate, phenytoin, carbamazepine, oxcarbazepine, primidone, levetiracetam): 6 (14.3%) Anticholinergics (trihexyphenidyl): 4 (9.5%) Botulinum toxin/splints: 3 (7.1%) Muscle relaxant (baclofen): 1 (2.4%) Other (isoniazid, dexamethasone): 2 (4.8%) No treatment/not given/not specified: 12 (28.6%) | Levodopa/levodopa-carbidopa: 5 (55.6%) Benzodiazepines/muscle relaxants: 1 (11.1%) Antipsychotics (risperidone trial): 1 (11.1%) None specific (improved with antiparasitic/ART only): 1 (11.1%) Not specified/not applicable: 1 (11.1%) | Not specified: 9 (100%) |
| Outcome | Complete recovery: 10 (23.8%) Marked/partial improvement (residual symptoms): 14 (33.3%) No significant improvement: 2 (4.8%) Death (any cause): 14 (33.3%) Other specific outcomes (AZT/radiotherapy): 2 (4.8%) | Persistent symptoms (including parkinsonism/dystonia): 3 (33.3%) Marked or complete recovery: 1 (11.1%) Partial improvement: 2 (22.2%) Death: 3 (33.3%) | Improvement/remission: 6 (66.7%) Fatal outcome: 2 (22.2%) Relapse/residual deficits: 1 (11.1%) |
| Follow-up duration | <3 months: 6 (14.3%) 3–<6 months: 8 (19.0%) 6–<12 months: 2 (4.8%) ≥1 year: 6 (14.3%) Until death: 10 (23.8%) Not specified/not stated/none: 10 (23.8%) | <6 months: 3 (33.3%) 6 months–<1 year: 2 (22.2%) 1–<3 years: 1 (11.1%) ≥3 years: 1 (11.1%) Not reported/unclear/post-mortem: 2 (22.2%) | < 6 months: 5 (55.6%) ≥ 6 months: 3 (33.3%) No follow-up: 1 (11.1%) |
| Proposed Pathogenic Mechanisms | Basal ganglia lesions/circuit disruption (including subthalamic, pallidal, thalamic involvement): 19 (45.2%) Cerebellar–thalamo–cortical/dentato–rubro–olivary pathway disruption: 6 (14.3%) Midbrain/red nucleus involvement (Holmes tremor, rubral tremor): 4 (9.5%) Diffuse/bilateral subcortical involvement (generalized movement disorders): 3 (7.1%) HIV encephalopathy/combined pathology (HIV + toxoplasmosis ± other lesions): 3 (7.1%) Functional/mixed organic–functional contribution: 1 (2.4%) Iatrogenic/catecholamine-induced: 1 (2.4%) Other specific (subcortical myoclonus, brainstem involvement without basal ganglia lesion): 1 (2.4%) Unclassified/not clearly stated in reports: 4 (9.5% | Basal ganglia lesions disrupting dopaminergic/motor circuits: 5 (55.6%) Post-infectious degeneration of nigrostriatal pathway: 2 (22.2%) Combined basal ganglia and thalamic circuit involvement: 1 (11.1%) Necrotizing toxoplasma encephalitis (glioma mimic) in immunocompetent: 1 (11.1%) | Reactivation – immunosuppression: 5 (55.6%) Direct invasion/neurotropism: 3 (33.3%) Immune defect (G6PD): 1 (11.1%) |
[i] AIDS: Acquired Immunodeficiency Syndrome; ART: Antiretroviral Therapy; CD: Cluster of Differentiation; CNS: Central Nervous System; CSF: Cerebrospinal Fluid; F: Female; G6PD: Glucose-6-Phosphate Dehydrogenase; HAART: Highly Active Antiretroviral Therapy; HIV: Human Immunodeficiency Virus; IQR: Interquartile Range; IV: Intravenous; M: Male; MRI: Magnetic Resonance Imaging; NA: Not Available/Not Applicable; PCR: Polymerase Chain Reaction; TMP-SMX: Trimethoprim–Sulfamethoxazole; VMAT: Vesicular Monoamine Transporter.