Bilateral MCP signal anomalies are associated with diverse conditions, including:

• Cerebrovascular events: Acute and chronic pontine infarcts, hematoma (Figure 1), Wallerian degeneration (2).
• Demyelinating disorders: Behçet’s disease (Figure 2), multiple sclerosis (MS) (Figure 3), Neuromyelitis optica spectrum disorders (NMOSD)  (Figure 4) (3).
• Metabolic conditions: Wilson’s disease (Figure 5), mitochondrial disorders (Figure 6) (4,5).
• Neurodegenerative diseases: Multiple system atrophy (MSA), spinocerebellar ataxias (SCA) (6,7).
• Genetic origins: Fragile X syndrome, LBSL (leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation), duplication lamin B1 (8).
• Enzymatic deficiencies: Adrenoleukodystrophy (ALD), cerebrotendinous xanthomatosis (9).
• Infectious causes: Progressive multifocal leukoencephalopathy (PML), post-infectious leukoencephalopathies (10,11).
• Metabolic crises: Hypoglycemia-induced leukoencephalopathy, axonal degeneration (12).
• Tumoral origins: Neoplastic or paraneoplastic syndromes involving the brainstem, lymphoma (Figure 7), Neurofibromatosis type 1 (Figure 8), (13).

2. Imaging Findings

MRI serves as the cornerstone for identifying MCP signal anomalies, with advanced techniques offering additional diagnostic insights.

2.1 T2-Weighted Imaging (T2WI)

• Primary Finding: Symmetrical or asymmetrical T2 hyperintensity is a hallmark across most etiologies (1,14).
• Symmetry: Symmetrical lesions suggest metabolic, genetic, or neurodegenerative conditions (4,5).
• Irregularity: Asymmetric or patchy hyperintensities often point to cerebrovascular or demyelinating disorders (2,3).

2.2 Diffusion-Weighted Imaging (DWI)

• Cerebrovascular Events:
• Acute infarcts show restricted diffusion and low ADC values, correlating with cytotoxic edema (2).
• Chronic infarcts and Wallerian degeneration demonstrate persistent T2 hyperintensity without restriction (15).
• Metabolic and Genetic Conditions:
• DWI changes are less common but can show subtle diffusion abnormalities due to cytotoxic or vasogenic edema (5,8).

2.3 Fluid-Attenuated Inversion Recovery (FLAIR)

• Enhanced Lesion Visibility: MCP lesions often appear more conspicuous on FLAIR sequences, aiding detection (3).
• Key Signs:
• "Hot cross bun" sign in MSA, indicative of pontocerebellar degeneration (6).
• Diffuse brainstem and MCP involvement in mitochondrial and metabolic disorders (4).

2.4 Contrast-Enhanced Imaging (CEI)

• Active Lesions: Enhancement indicates active inflammation, as seen in MS or infectious leukoencephalopathies (3,11).
• Non-Enhancing Lesions: Chronic neurodegenerative or stable metabolic diseases lack enhancement (7).

2.5 Magnetic Resonance Spectroscopy (MRS)

• Metabolic Signatures:
• Elevated lactate peaks are characteristic of mitochondrial diseases (5).
• Reduced N-acetylaspartate (NAA) in neurodegenerative and demyelinating conditions reflects neuronal loss (4,7).

2.6 Susceptibility-Weighted Imaging (SWI)

• Mineral Deposition: Abnormalities in Wilson’s disease due to copper accumulation (4).
• Microbleeds: Often observed in neurodegenerative diseases, helping distinguish from demyelinating conditions (6).

2.7 Diffusion Tensor Imaging (DTI)

• Microstructural Integrity:
• Reduced fractional anisotropy (FA) in MCPs indicates disrupted white matter, seen in neurodegenerative and genetic conditions (7,8).
• Advanced Metrics: DTI metrics can aid in differentiating conditions like MSA and spinocerebellar ataxias (7).

2.8 Quantitative MRI Techniques

Atrophy Detection: Subtle volume loss in MCPs is detectable in advanced stages of neurodegenerative conditions (6).

Microstructural Analysis: Quantitative approaches reveal microstructural damage before conventional imaging abnormalities become apparent (7).

The table summarizes the etiologies of bilateral middle cerebellar peduncle (MCP) lesions and their distinguishing MRI features.