Differential diagnosis of bilateral abnormalities of basal ganglia and thalamus

This is not a pure radiological discussion where we discuss rare and exotic diseases. Often, patients will present with non specific symptoms eg fatigue, dizziness or seizure and because you do not have an obvious diagnosis, CT/MRI scans will be done.

What if you find out that this patient has CT like this?


Or MRI like this?


Anatomy of basal ganglia and thalamus

From https://fhs122anatomyelab.wordpress.com/

From http://unpa.memberlodge.com/basal_ganglia_in_pain_and_analgesia

At MR imaging, caudate nucleus and putamen are normally isointense to cortical gray mater.

Globus pallidus is slightly hypointense, due to progressive calcification as one ages.

Lentiform nucleus may demonstrate enlarged perivascular spaces (if large enough can mimic arachnoid cyst) and may also show age-related calcification.


Functions of basal ganglia are complex

  • Metabolically active, rich in mitochondrial and needs lots of glucose and oxygen
  • Therefore susceptible to systemic insult.

Blood supply of basal ganglia

  • Artery: lateral and medial lenticulostriate arteries from MCA, thalamus is supplied by perforating arteries from PCA
  • Venous system: drainage into deep venous system (superior and inferior thalamostriate veins –> basal vein of Roenthal and internal cerebral veins –> great vein of Galen –> sinus confluence and to transverse sinus

Differential diagnosis of bilateral abnormalities of basal ganglia and thalamus

Toxic poisoning

  • CO, cyanide and methanol: these three impair mitochondrial cellular respiratory enzymes
    – CO and cyanide block electron transport chain
    – methanol is converted to toxic formaldehyde; optic neuritis is the initial presentation
  • CO has predilection for globus pallidus. Delayed leukoencephalopathy may also be seen.
  • Methanol poisoning may demonstrate diffuse white mater edema

Liver disease

  • Also tends to involve globus pallidus (T1 hyperintensity), maybe due to deposition of manganese (paramagnetic)
  • In acute hepatic encephalopathy, ammonia deposition in brain causes diffuse edema with T2 hyperintensity in basal ganglia and insular cortex. DWI shows restricted diffusion (bright), as do most of the pathologies we will discuss here do.

Non ketotic hyperglycemia

  • Typically dx is not a problem, but if CT is done, may see bilateral caudate/pallidal hyperattenuation.
  • MRI: T1 hyperintensity, mechanism is unknown but perhaps there maybe deposition of blood, calcium or other minerals
    (other t1 hyperintensity is liver cirrhosis)


  • Disgnosis is not hard, but can be missed in patients with coma.
  • Bilateral T2 hyperintensities in basal ganglia WITH sparing of thalamus, subcortical white mater and cerebellum.

    Hypointensity in T1 in hypoglycemic brain injury (from http://radiopaedia.org/cases/hypoglycemic-brain-injury)
    Looking at this, it maybe argued that perhaps basal ganglia is isointense to gray mater but looking at T1 (hypointense) and DWI (restricted diffusion) will make the diagnosis clearer.Figure
    Restricted diffusion on DWI


  • Normally affects grey mater due to its high metabolic requirement for oxygen and glucose to supply a large number of synapses.
  • CT will show diffuse edema, decreased attenuating of grey mater with loss of grey-white differentiation (like stroke) and bilateral hypoattenuating areas in basal ganglia (cerebellum, brainstem are normally spared)
  • Reversal sign: white mater and basal ganglia become more hyperdense than the grey mater with diffuse edema
    – Postulated to be due to diffuse edema causing rise of ICP and blockade of venous drainage by deep medullary veins

    Location of deep medullary veins (copied from http://journal.frontiersin.org/article/10.3389/fnagi.2014.00144/full)
    Normal CT
    Reversal sign
  • White cerebellum sign due to diffuse cerebral edema causing the spared cerebellum to appear brighter
    White cerebellum sign
  • White cerebellum sign and reversal sign = very bad prognosis

Wilson disease

  • Predilection to putamen, but can involved other parts of basal ganglia.
  • If thalamus is involved, typically confine to ventrolateral aspect.

Osmotic myelinolysis

  • Clinical presentation varies: deceased level of conscious, ataxia, spastic hemiparesis etc
  • Not only involving pons, but also basal ganglia and cerebelllum  (sites of distribution of oligodendrocytes)
    Typical appearance of pons in osmotic myelinolysis: hyperintensity in the central pons

Wernicke encephalopathy

  • T2 hyperintensity in mamillary bodies, medial thalamus (compared to Wilson’s disease) and periaqueductal areas.


  • Prior disease, most common is sporadic form, variant form is called mad cow disease, other tyoes include iatrogenic and familial. The word “spongiform” refers to the sponge-like appearance of the brain tissue.
  • Restricted diffusion (due to spongiform neuronal degeneration) is more sensitive than T2 weighted sequence to detect CJD.
  • Classical sign is pulvinar sign (T2 hyperintensity in pulvinar)

Deep cerebral venous thrombosis

  • Normally as an extension from superficial cerebral venous thrombosis.
  • Simultaneous involvement of basal ganglia and thalamus should prompt the search for other signs of venous thrombosisFigure
    MRV shows absence flow in basal vein of Rosenthal, internal cerebral vein and great vein of Galen
    – CT: empty delta sign, dense clot sign, hemorrhage in typical locations as shown in the diagram above
    Dense clot sign in cortical veins.
    Empty delta sign
  • MRI: loss of flow void, hyperintensity thrombus

Pontine infarction

  • Normally due to basilar artery occlusion (gives paramedian branches and AICA that supply pons). Pontine infarction typically results in coma and constricted pupil.
    Occlusion of rostral part of basilar artery
  • If there is pontine hemorrhage, suspect hypertensive ICB.

Neuro behcet disease

  • Symmetrical basal ganglia involvement with T2 hyperintensity, T1 hypointensity & enhance on contrast (vasculitis causing breakdown of the endothelial layer)

Flavivirus encephalitis

  • JE virus commonly causes bilateral but ASYMMETRICAL involvement of posteromedial thalamus

CNS toxoplasmosis

  • Hypointense to isointense lesion on T2 (compared to the rest which are normally hyperintense, ie closer to CSF)
  • Ring enhancement maybe seen following contrast administration
  • In HIV-AIDS, maybe presented similarly to CNS lymphoma

Primary CNS lymphoma

  • Same as toxoplasmosis, T2 hypo/isointensity. due to high cellularity
  • Commonly involves periventricular, corpus callosum and basal ganglia areas.
  • Vivid enhancement but in HIV-AIDS can have ring enhancement similar to toxoplasmosis, and like toxo can be multiple.
  • Identifying other lesions in periventricular areas may be helpful in helping to distinguish from toxoplasmosis.

Thalamic glioma

  • Rare, and although it’s low grade, it has poor prognosis due to its deep location



  • Metabolic
    – Toxic poisoning: CO favours globus pallidus, methanol has diffuse white mater swelling
    – Liver disease: T1 hyperintensity
    – Hypoglycemia
    – Non-ketotic hyperglycemia: T1 hyperintensity
    – Wernicke’s encephalopathy: involves mammilary body, medial thalamus and peri-aqueductal areas
    Wilson’s disease: favours globus pallidus and ventrolateral thalamus
  • Hypoxia
    – HIE : diffuse cerebral edema sparing cerebellum and brainstem, gray mater involvement, reversal sign and white cerebellum sign
  • Osmotic myelinolysis: not only pons involvement, but also basal ganglia and cerebellum
  • Infarction (venous/arterial)
    – Venous: look for subtle signs of superficial CVT
  • Degeneration (CJD)
    – Restricted diffusion, pulvinar sign (medial thalamus similar to Wernicke’s)
  • Infection
    – Flavivirus: JE virus favours thalamus (posteromedial thalamus)
    – Toxoplasmosis: T2 hypointense/isointense lesion, ring enhancement
  • Neoplasm
    – Lymphoma: T2 hypo/isointense, vivd enhancement
    – Glioma

These are some of the conditions in which I think neuroimaging can really narrow down the ddx:

If it’s bilateral and symmetrical:

  • Metabolic: Intoxication, Wernicke’s, rarely Wilson’s
    – Most likely hypoglycemia, nonketotic hyperglycemia and hepatic encephalopathy would not be missed., but remember that metabolic toxins (eg ammonia and too high glucose) can cause abnormalities in basal ganglia and thalamus.
  • Infarction
    – Pontine infarction is normally quite obvious in CT
    – Pontine CVT: normally hemorrhage will present, or other signs of superficial CVT in CT
  • Iatrogenic (Osmotic myelinolysis)
    – Normally not difficult diagnostically as  serial sodium level is often obtained to determine the rate of correction in hypoNa,

If diffuse cerebral edema is present and patient had resp/cardiac failure with shock –> HIE

  • There may also be pseudo SAH pattern in CT

If is bilateral but asymmetrical: normally it is due to infection or infiltration (neoplasm)

Mnemonic to remember the causes of basal ganglia & thalamus bilateral abns: 7Is

  • Intoxication (toxic, Wernicke)
  • Inborn (Wilson’s, mitochondrial diseases – not mentioned here because they are rare)
  • Iatrogenic (osmotic myelinolysis)
  • Infarction
  • Ischemia
  • Infection
  • Infiltration (neoplasm)

Take home messages

  1. As you can see, bilateral basal ganglia and thalamus abnormalities are associated with many many conditions.
  2. Bilateral symmetric: systemic/metabolic
    Bilateral but asymmetric/focal: infection/neoplasm


Amogh N. Hegde, MD, FRCR, Suyash Mohan, MD, PDCC, Narayan Lath, MD, FRCR, and C. C. Tchoyoson Lim, MMed, FRCP. Differential Diagnosis for Bilateral Abnormalities of the Basal Ganglia and Thalamus. RadioGraphics 2011;31:5-30


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