European Radiology: Use of iron-sensitive MRI in differentiating hereditary spastic paraplegia from other motor neuron diseases.

Hereditary spastic diplegia (HSP) is a heterogeneous group of rare inherited neurodegenerative disorders characterized by slow-onset spasticity, hyperreflexia, and lower extremity weakness
.
In addition to upper motor neuron (UMN) damage, clinical manifestations can include other neurologic and extraneurologic features, and HSP is accordingly classified as simple and complex
.

Progressive spastic weakness of the lower extremities is a predominant feature in patients with HSP, but may also be the predominant clinical feature
in patients with primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS).
Although a family history of progressive gait disturbance, mild dorsal column dysfunction, craniocerebral acrosis, and lower extremity spasticity is the main clue that HSP is higher than PLS and ALS, the differential diagnosis between these three motor neuron disorders (MND) is challenging, especially in the early stages
of sporadic adult UMN syndrome with onset of lower extremity symptoms.
Therefore, genetic testing is the basis for diagnosing HSP; However, in all suspected cases, 51-71% lack genetic diagnosis
.
In this setting, identifying simple and reliable imaging markers that distinguish HSP from PLS and ALS is important
for prognosis and genetic counseling for relatives.

In recent years, more and more literature has recognized the role of advanced MRI techniques in detecting UMN degeneration in ALS patients, especially T2*-weighted imaging at high and ultra-high magnetic field intensities can reveal UMN involvement
at the individual subject level.
Iron accumulation within activated intracortical microglia results in a shortened T2* relaxation time, with low-signal edges
visible in the deep layers of the cortex.
This abnormal iron deposition has been described in ALS but is never mentioned
in neuropathological reports of HSP cases.

Recently, a study published in the journal European Radiology used iron-sensitive MR sequences, namely three-dimensional T2* weighted imaging, to explore the specific imaging manifestations of the primary motor cortex in HSP patients, and compared the frequency of signal changes in HSP patients with PLS and ALS patients, providing an imaging basis
for further clarifying the pathophysiology and disease progression of HSP.

This study included 3-T MRI scans from 23 patients with HSP, 7 patients with lower extremity-onset PLS, 8 patients with lower extremity and generalized UMN-onset ALS (UMN-ALS), and 84 patients with ALS with any other clinical manifestations
.
On the three-dimensional T2*-weighted image, PMCs were visually assessed as normal, mildly low-signal, or markedly low-signal, and the frequency distribution differences
in signal intensity between different diseases were studied.

Significantly low PMC signal
was seen in 3/22 HSP patients (14%), 7/7 PLS patients (100%), 6/8 UMN-ALS patients (75%), and 35/84 ALS patients (42%).
The frequency distribution of normal signal intensity, mildly low signal, and significantly low signal in HSP patients differs from that in patients with PLS, UMN-LS, and ALS (P<0.
01 in all cases
).

Figure T2*weighted image
of the levels of the paracentral lobular (A-D) and hand nodal area (A′-D′) of two HSP patients (A,A′ and D,D′), one PLS patient (B,B′), and one UMN-ALS patient (C,C′).
。 The deep primary motor cortex in most HSP patients had equal signaling with the posterior central cortex (black arrows in A and A′), while low signal
was evident in all PLS patients (black arrows in B and B′), 6 UMN-ALS patients (black arrows in C and C′), and 3 HSP patients (black arrows in D and D′).
As a serendipitous finding, patients with UMN-ALS have superficial arachnoid lesions (arrows of C)

This study suggests that iron-sensitive magnetic resonance imaging of the primary motor cortex can provide additional useful information for the clinical diagnosis and treatment of patients with sporadic adult-onset UMN syndrome, especially when
the lower extremity is the only or first affected body area.

Original source:

Mirco Cosottini,Graziella Donatelli,Ivana Ricca,et al.
Iron-sensitive MR imaging of the primary motor cortex to differentiate hereditary spastic paraplegia from other motor neuron diseases.
DOI:10.
1007/s00330-022-08865-6