7-year-old male child, developmentally appropriate for age, came with complaints of fever for 4days(started on 3/05/2026), non-documented, low to moderate grade, not associated with chills or rigors, relieved on medications. Child was afebrile for 3 days ,and spiked fever again. On day 2 of fever child developed rashes, initially started from face → trunk → limbs, including palms and soles Self-resolved after 4 days. Blood investigations were done and was told to have typhoid fever. No medications were given.for the above complaints child was admitted at a hospital at Davangere On Day 2 of admission, child developed weakness of bilateral lower limbs in the forms of inability to walk and also child had reduced speech output. Took DAMA and went to another hospital. Then child developed weakness initially, able to lift hand, inability to move leg → progressed to complete paralysis and inability to speak, but able to open mouth and take liquids orally. No history of headache/vomiting. No history of bowel and bladder incontinence. No history of deviation of face. No history of regurgitation. No history of seizures/abnormal movements. No history of loss of consciousness. No history of trauma. No history of cough/cold. History of contact with cat which died of ?rabies is present. Child was taken to a nearby hospital. No signs of raised ICP. Tone increased in all four limbs with brisk reflexes. Given empirical antibiotics (Ceftriaxone and Vancomycin). WIDAL positive * CSF analysis: Cell count 22, lymphocytes, protein 32mg/dl, glucose-65mg/dl,culture of csf- no growth * Acyclovir was started. MRI brain: Bilateral symmetrical basal ganglia hyperintensities involving cautdate and putamen . MRI spine- normal CSF: AES panel-HSV, JE, Enterovirus negative autoimmune panel – negative. Metabolic ammonia and lactate – normal. CSF culture – no growth. Scrub typhus IgM – negative. Dengue IgM and NS1 negative Started on Inj. Methylprednisolone pulse regimen, given for 3 days . No improvement/no deterioration. Child was later referred to Indira Gandhi institute of child health for further evaluation. What are the differentials
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bilateral basal ganglia hyperintensity encephalitis children differential diagnosis
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bilateral basal ganglia caudate putamen hyperintensity encephalitis child differential diagnosis fever rash India
Now I have enough data to construct a thorough, well-organized differential. Let me compile it.
Differential Diagnosis
This is a complex pediatric neurological case with a distinctive phenotype. Let me break down the key features that should anchor your differentials:
Anchor Features:
- 7-year-old male, previously well
- Febrile illness + rash (face → trunk → limbs including palms/soles, self-resolving after 4 days)
- Biphasic fever course (fever - 3-day afebrile gap - fever again)
- WIDAL positive
- Rapidly progressive quadriparesis (LMN → UMN pattern?) + aphasia/reduced speech
- Bilateral symmetrical basal ganglia hyperintensities - caudate + putamen specifically
- MRI spine: normal
- CSF: mild lymphocytic pleocytosis (22 cells), normal protein (32), normal glucose; culture sterile
- AES panel (HSV, JE, enterovirus) negative; autoimmune panel negative; metabolic screen normal
- Contact with a cat that died of suspected rabies
- No improvement with methylprednisolone pulse
TIER 1 - Most Likely Differentials
1. Para/Post-Infectious Basal Ganglia Encephalitis (Streptococcal / Mycoplasma / Other)
This is the strongest fit for this case. A well-described entity in Indian pediatric literature (Indian Pediatrics 1997 series) with:
- Post-febrile onset in children >3 years
- Bilateral caudate + putamen T2 hyperintensities on MRI (identical to this case)
- Movement disorder and/or neurological deficit following febrile illness
- CSF: mild lymphocytic pleocytosis, normal protein/glucose
- Can follow pharyngitis, viral fever, or bacterial illness
This overlaps with Sydenham's chorea territory (Group A Strep), though the motor presentation here is predominantly weakness + aphasia rather than chorea.
Workup to add: ASO titre, anti-DNase B, throat swab/culture, echocardiogram.
2. Typhoid Encephalopathy with Basal Ganglia Involvement
Salmonella typhi causes a broad range of neurological complications:
- Encephalopathy, acute psychosis, cerebellar dysfunction, motor weakness
- A rare but reported form involves direct CNS vasculitis or immune-mediated basal ganglia injury
- WIDAL positivity in context is supportive, though sensitivity/specificity is limited
- The biphasic fever pattern and rash (rose spots - though classically on trunk, not always palms/soles) is consistent
- No antibiotic treatment was given for typhoid initially - raises concern for ongoing bacterial toxin-mediated brain injury
Caveat: The caudate + putamen pattern and the degree of motor deficit is atypical for typhoid alone. Consider typhoid as a trigger for immune-mediated basal ganglia encephalitis rather than direct causation.
Workup: Blood culture (if not done), typhoid IgM (Tubex/ELISA), repeat WIDAL titres.
3. Anti-Dopamine-2 Receptor (D2R) Antibody Encephalitis / Autoimmune Basal Ganglia Encephalitis
- A specific autoimmune encephalitis targeting dopamine-2 receptors preferentially found in the basal ganglia
- Presents in children with: abnormal movements, parkinsonism, oculogyric crises, psychiatric features, brainstem dysfunction, neurological regression
- MRI: bilateral basal ganglia T2 hyperintensities (identical to this case)
- Can follow streptococcal, Mycoplasma, or other infections (post-infectious trigger)
- CSF: mild lymphocytosis, normal protein (fits this case perfectly)
- The autoimmune panel done may not have included D2R antibodies - this is a specialized test not in routine panels
This diagnosis must be specifically tested for: anti-D2R antibodies in serum and CSF.
(Harrison's 22E; Bradley & Daroff's Neurology)
4. Acute Disseminated Encephalomyelitis (ADEM) with Basal Ganglia Predominance
- Post-infectious demyelinating syndrome, classically in children
- Basal ganglia + thalamus involvement is particularly common in pediatric ADEM (Grainger & Allison; Harrison's 22E)
- Bilateral symmetrical pattern well described
- Can cause motor deficits, aphasia, altered consciousness
- CSF: lymphocytic pleocytosis, mildly elevated protein (this case fits)
- Typically monophasic; treatment: steroids (but this child showed no improvement)
Against this diagnosis: The MRI in classical ADEM typically shows multifocal white matter lesions with or without gray matter involvement. Pure bilateral basal ganglia involvement without white matter lesions is atypical for ADEM. However, basal ganglia-predominant ADEM exists and must be considered.
Workup: Review MRI for white matter involvement; MRI with gadolinium if not done; repeat MRI at 3 months.
TIER 2 - Important to Exclude
5. Japanese Encephalitis (JE) - Incomplete or Atypical Form
- JE classically involves thalamus bilaterally; basal ganglia (caudate/putamen) involvement occurs but is secondary
- AES panel was negative for JE - however, early disease or low viral load may give false negatives depending on timing of testing
- India is endemic for JE (Karnataka has reported cases)
- Clinical picture: fever, rash (though rash is not typical of JE), motor deficits, altered consciousness
- MRI: T2 hyperintensity in thalami > basal ganglia (Harrison's; Goldman-Cecil)
Recommendation: Repeat JE IgM if initial test was done in very early disease (within first 4 days). Also check JE vaccination history.
6. West Nile Virus / Other Arboviral Encephalitis
- West Nile virus: bilateral thalamus + caudate + lentiform nucleus involvement is characteristic (per Radiographics differential)
- Presents with febrile illness, rash (maculopapular, including trunk/extremities), progressing to encephalitis
- Adams & Victor's: "Signal changes in the basal ganglia are described particularly with Japanese B virus group, West Nile, EEE, and rabies"
7. Rabies Encephalitis (Furious or Paralytic - Non-classical)
- This child had known contact with a cat that died of suspected rabies - this is a critical red flag
- Paralytic (dumb) rabies: ascending flaccid paralysis, dysarthria/aphasia, preserved consciousness early - closely mimics this presentation
- However: MRI in rabies typically shows brainstem, thalamic, hippocampal, and cortical hyperintensities, not predominantly caudate/putamen
- CSF: lymphocytic pleocytosis (mild), normal or slightly elevated protein
- No bowel/bladder incontinence, no hydrophobia mentioned - atypical; but absence doesn't exclude it
- Rabies also involves basal ganglia - specifically thalamus and brainstem - per Adams & Victor's
Urgent workup: Rabies DFA (direct fluorescent antibody) on skin biopsy (nape of neck), saliva RT-PCR, serum/CSF rabies antibodies (if vaccinated). This is a diagnosis that cannot be missed.
8. Acute Necrotizing Encephalopathy (ANE)
- Follows viral infections (influenza, COVID-19, HHV-6, others)
- Bilateral thalamic and basal ganglia lesions (T2 hyperintensity + restricted diffusion)
- Typically very rapid deterioration with seizures and hyper-reflexia
- CSF: usually normal or mildly elevated protein
- Bradley & Daroff's: "imaging evidence of bilateral thalamic/basal ganglia/brainstem inflammation and edema"
- Against: Usually involves thalami prominently; course is typically more fulminant; no restricted diffusion mentioned in this case
9. Subacute Sclerosing Panencephalitis (SSPE)
- Chronic progressive measles virus encephalitis
- Typical age: school-going children
- Progressive intellectual deterioration, myoclonic jerks, EEG showing periodic complexes
- MRI: basal ganglia and periventricular white matter changes can occur
- Measles serology/CSF measles antibody titres should be checked
- The relatively acute onset and febrile trigger makes SSPE less likely, but early SSPE can mimic acute encephalitis
10. Enterovirus A71 (EV-A71) Encephalitis
- AES panel was reportedly negative for "enterovirus" - but EV-A71 is a specific enterovirus subtype
- EV-A71 causes hand-foot-mouth disease (HFMD) - rash on palms and soles is characteristic
- Followed by brainstem and basal ganglia encephalitis in children
- CSF: lymphocytic pleocytosis (mild), normal protein
- Harrison's explicitly mentions: "Significant involvement of deep gray matter, including basal ganglia and thalamus, should also suggest possible flavivirus infection... EV-A71"
The rash on palms and soles in this child strongly suggests HFMD followed by EV-A71 encephalitis. This must be specifically excluded.
Workup: Throat swab, rectal swab, and CSF for EV-A71 PCR (distinct from generic enterovirus PCR on AES panel).
11. Leptospirosis with CNS Involvement / Autoimmune Basal Ganglia Encephalitis Post-Leptospirosis
- A published case (PMID: 36352619) from India reports basal ganglia autoimmune encephalitis following leptospirosis
- Leptospirosis is endemic in Karnataka
TIER 3 - Metabolic/Other (Lower Priority Given Normal Metabolic Screen)
| Diagnosis | Why Consider | Why Less Likely |
|---|---|---|
| Leigh Syndrome | Bilateral caudate/putamen T2 hyperintensity in children | Metabolic screen (lactate, ammonia) normal; no prior developmental delay |
| Wilson's disease | Bilateral putamen/caudate involvement | Age 7 is early; no hepatic involvement described |
| Kernicterus (delayed) | Basal ganglia injury | Age inappropriate; no jaundice history |
| Organic aciduria | Basal ganglia lesions | Metabolic screen normal |
Summary Table - Prioritized
| Priority | Diagnosis | Key Supporting Feature |
|---|---|---|
| High | Anti-D2R autoimmune basal ganglia encephalitis | Post-infectious, bilateral caudate+putamen, CSF profile, age |
| High | EV-A71 encephalitis (HFMD-related) | Rash on palms/soles - pathognomonic clue |
| High | Para/post-infectious BGE (Strep/Myco) | Indian case series, identical MRI pattern |
| High | Typhoid-triggered immune BGE | WIDAL+, untreated, biphasic fever |
| URGENT | Rabies (paralytic form) | Cat contact with suspected rabies - must not miss |
| Medium | ADEM (basal ganglia-predominant) | Post-infectious demyelination, steroid trial |
| Medium | JE - atypical/early (retest) | Endemic region, AES timing matters |
| Medium | West Nile / Arboviral | Bilateral caudate/lentiform pattern |
| Lower | SSPE | Age-appropriate, check measles titres |
| Lower | ANE post-viral | Typical pattern different |
Critical Workup to Request at IGICH
- EV-A71 specific PCR (throat/rectal swab + CSF) - palms/soles rash is a major clue
- Anti-D2R antibodies (serum + CSF) - most specific test for autoimmune BGE
- ASO titre + anti-DNase B - post-streptococcal trigger
- Rabies workup - skin biopsy DFA, saliva PCR, serum antibodies (given cat contact)
- Repeat JE IgM - if first test was early in disease
- Measles IgG + CSF measles antibody - rule out SSPE
- Blood culture (Salmonella) + typhoid IgM ELISA (more specific than WIDAL)
- EEG - periodic complexes (SSPE); delta brush (anti-NMDAR); background slowing
- MRI with gadolinium + DWI review - restricted diffusion pattern helps narrow (ANE vs. autoimmune vs. infectious)
- Leptospira IgM (endemic in Karnataka)
The single most important diagnostic lead here is the rash involving palms and soles - this is the hallmark of Hand, Foot, and Mouth Disease caused by EV-A71, which is the leading cause of brainstem/basal ganglia encephalitis in children in South and Southeast Asia and would not be picked up by a generic enterovirus PCR panel. Combined with anti-D2R antibody testing (specialized autoimmune test not in routine panels), these two investigations are most likely to yield the diagnosis.
Lepzig scire
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Leipzig scoring system Wilson's disease criteria table 2022
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Got the full table. Here is the complete Leipzig scoring system:
Leipzig Scoring System for Wilson's Disease
Developed at the 8th International Meeting on Wilson's Disease, Leipzig (2001). Endorsed by EASL, AASLD, and ESPGHAN guidelines.
Scoring Table
| Parameter | Finding | Points |
|---|---|---|
| Kayser-Fleischer rings | Present | +2 |
| Absent | 0 | |
| Neurological symptoms | Severe | +2 |
| Mild | +1 | |
| Absent | 0 | |
| Serum ceruloplasmin | Normal (>0.2 g/L) | 0 |
| 0.1 - 0.2 g/L | +1 | |
| <0.1 g/L | +2 | |
| DAT-negative (Coombs-negative) hemolytic anemia | Present | +1 |
| Absent | 0 | |
| Liver copper (no cholestasis) | >5x upper limit of normal | +2 |
| >Normal but <5x ULN | +1 | |
| Normal | -1 | |
| Positive copper stain (if liver copper not quantified) | +1 | |
| 24-hour urinary copper (no acute hepatitis) | >2x upper limit of normal | +2 |
| 1-2x upper limit of normal | +1 | |
| Normal | 0 | |
| Positive penicillamine challenge test* | +2 | |
| ATP7B mutation analysis | Two pathogenic mutations (both chromosomes) | +4 |
| One pathogenic mutation | +1 | |
| No mutations identified | 0 |
*Penicillamine challenge: urine copper >25 µmol/24h after 500 mg D-penicillamine twice daily, used mainly in children.
Interpretation
| Total Score | Interpretation |
|---|---|
| ≥ 4 | Wilson's disease highly likely - diagnosis established |
| 3 | Wilson's disease possible - further workup required (e.g., liver biopsy) |
| ≤ 2 | Wilson's disease unlikely |
Key Points
- Maximum possible score is technically >4 in several combinations, so the system is not additive in a strict ceiling sense - the cutoff of 4 is the diagnostic threshold.
- Normal liver copper (−1 point) is an important negative: it actively lowers the score and argues against the diagnosis.
- KF rings alone are not diagnostic - they can be absent in up to 50% of patients with hepatic-only presentation.
- The score should not be used as the sole method for diagnosis or exclusion - clinical context is essential.
Modified Leipzig Score (Nagral et al., 2019 - Indian Association)
The modified version adds two additional parameters:
| Added Parameter | Finding | Points |
|---|---|---|
| Brain MRI | Typical features (basal ganglia T2 hyperintensity, "face of giant panda" sign) | +2 |
| Atypical/non-specific | +1 | |
| Family history | Sibling with confirmed WD or unexplained hepatic/neurological death | +1 |
The modified score also removes hepatic copper quantification, as serum ceruloplasmin + urinary copper + genetic testing are considered sufficient in most cases.
Relevance to the Case Above
In the 7-year-old discussed earlier, Wilson's disease was listed as a lower-tier differential. Applying the Leipzig score:
- Age 7 is early but not impossible for Wilson's (usual presentation: 5-35 years)
- Bilateral caudate + putamen T2 hyperintensity on MRI: typical for neurological Wilson's (+2 on modified score)
- Workup needed: slit-lamp exam for KF rings, serum ceruloplasmin, 24-hour urine copper - these three tests together can substantially shift the Leipzig score and either confirm or reasonably exclude Wilson's disease.
- Yamada's Textbook of Gastroenterology, 7th ed.
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