To achieve optimal imaging of the limbic system, the following MRI sequences and parameters are recommended:

1. High-resolution 3D T1-weighted imaging
   • Purpose: To assess structural abnormalities such as atrophy or malformation (5).
   • Parameters: Slice thickness 1-1.5 mm, no gap, field of view (FOV) 220–250 mm.
2. T2-weighted imaging
   • Purpose: To detect lesions, hyperintensities, and signs of inflammation (6).
   • Parameters: Slice thickness 4-5 mm, FOV 220–250 mm, TE: 100-120 ms.
3. FLAIR (Fluid Attenuated Inversion Recovery)
   • Purpose: To identify hyperintensities associated with inflammatory or infectious conditions (6–8).
   • Parameters: Slice thickness 4-5 mm, TE: 120-140 ms, inversion time (TI): 2000-2500 ms.
4. Diffusion-weighted imaging (DWI)
   • Purpose: To identify cytotoxic edema in conditions like encephalitis and hypoxic injury (9).
   • Parameters: Slice thickness 5-6 mm, b-value of 1000 s/mm², FOV 220-250 mm.
5. Susceptibility-weighted imaging (SWI)
   • Purpose: To detect microhemorrhages, especially in trauma or hemorrhagic conditions.
   • Parameters: Slice thickness 2-3 mm, TE 40–60 ms, FOV 220 mm.
6. Post-contrast imaging (if indicated)
   • Purpose: For detecting enhanced lesions, especially in cases of inflammation, infection, or tumors.
   • Sequence: T1-weighted with contrast (Gadolinium), slice thickness 4-5 mm, FOV 220–250 mm.

Imaging Findings

Etiologies Affecting the Limbic System

1. Genetic Causes : (Figure 4) 

• Congenital Malformations: Hippocampal malrotation (unilateral or bilateral), agenesis of the fornix. Associated findings include cortical dysplasia (10,11).
• Neurodevelopmental Disorders:
  • LIS1 mutation: Thin or dysplastic cortex (12).
  • DCX mutation: Smoothened gyral pattern (13).

2. Infectious Causes

• Viral Infections: (Figure 5-8) 
  • Herpes Simplex Virus Encephalitis (HSV): Hyperintense signal on T2/FLAIR in medial temporal lobes (14).
  • West Nile Virus (15).
• Chronic Infections:
  • Tuberculosis: Nodular enhancement, caseating necrosis in basal ganglia (16).
  • Neurosyphilis: Atrophic changes, hypersignal in limbic and basal regions (17).
    • Others : Whipple’s disease, and HIV primary infection, Dengue (18).

3. Traumatic Causes

• Diffuse Axonal Injury (DAI): Microhemorrhages on SWI; focal T2 hyperintensities in the hippocampus and fornix (19).
• Post-Traumatic Encephalopathy: T1 hypointensity with volumetric loss in limbic structures, diffuse cortical thinning (20).

4. Inflammatory/Autoimmune Causes

• Neuroinflammatory Syndromes: (Figure 9-12) 
  • Anti-NMDA receptor encephalitis: Limbic T2 hyperintensities with cortical/subcortical involvement (21).
• Multiple Sclerosis: Periventricular and juxtacortical T2 lesions, sparing basal ganglia (22).

5. Metabolic etiologies

• Hypoglycemia: Restricted diffusion in the hippocampus (23).
• Wilson's Disease: T2 hyperintensities in basal ganglia and thalamus (24). (Figure 13) 

• Biotinidase deficiency: Can lead to limbic and basal ganglia involvement (25).

• Thiamine (Vitamin B1) deficiency: Causes Wernicke’s encephalopathy, affecting the mammillary bodies, thalamus, and hippocampus (26) (Figure 14).

• Maple Syrup Urine Disease (MSUD): Involves gray matter structures, including the thalamus and limbic system (27).
• Phenylketonuria (PKU): Primarily affects the cortex and basal ganglia, but rare limbic involvement is reported (28).
• Glutaric Aciduria Type I: Affects the basal ganglia and can extend to limbic structures (29).
• Methylmalonic and Propionic Acidemia: Cause deep gray matter involvement, potentially affecting the limbic system (30).
• Fabry Disease: Can involve white matter and limbic structures, leading to cognitive impairment (31).
• Metachromatic Leukodystrophy & Krabbe Disease: Cause demyelination that may extend to the hippocampus and limbic circuits (32).
• Mitochondrial Encephalopathies (MELAS, Leigh, POLG-related disorders): Frequently involve the limbic system, basal ganglia, and brainstem (33).
• Hyperammonemia (Urea Cycle Disorders): Leads to diffuse brain dysfunction, including limbic system involvement (34).

6. Toxic Encephalopathies:

• Carbon monoxide poisoning: Globus pallidus and hippocampal diffusion restriction (35). (Figure 15) 
•  
• Wernicke’s encephalopathy: Mammillary body and thalamic T2 hyperintensities (36,37).

The limbic system can be affected by both primary and secondary brain tumors. Limbic gliomas, particularly low-grade gliomas and glioblastomas, may involve the hippocampus, cingulate gyrus, and amygdala, leading to seizures and cognitive dysfunction. Primary CNS lymphoma frequently involves deep gray matter, including the thalamus and limbic structures, often presenting with homogeneous enhancement and restricted diffusion on DWI (38). Metastases from lung, breast, and melanoma can also involve the limbic system, presenting as multifocal or solitary lesions with variable enhancement (38). Paraneoplastic limbic encephalitis, associated with anti-Hu, Ma2, and anti-NMDA receptor antibodies, may mimic limbic tumors but typically presents with bilateral T2/FLAIR hyperintensities without mass effect.