The diagnostic value of midbrain hyperechogenicity in ALS is limited for discriminating key ALS differential diagnoses.

Andreas Hermann,Mario Leimert,Jochen Schaefer,Jan Kassubek,Panteha Fathinia,Alexander Storch,Tordis Leimert,Ulrike Reuner,Albert C Ludolph

doi:10.1186/s12883-015-0280-x

Andreas Hermann, Mario Leimert + Show 7 more

Open Access

https://doi.org/10.1186/s12883-015-0280-x

Copy DOI

Abstract

BackgroundHyperechogenicity of the substantia nigra was recently reported in patients with sporadic ALS with a frequency similar to PD. Data on the diagnostic utility compared to key differential diagnoses of ALS do not exist yet.MethodsWe prospectively enrolled 43 patients with ALS, 29 with myasthenia gravis, 25 patients with inflammatory neuropathy, and 13 with cervical canal stenosis. All patients were examined by a blinded investigator using transcranial B-mode sonography planimetrically measuring hyperechogenic areas of the midbrain representing the substantia nigra.ResultsMean midbrain hyperechogenic area was increased in ALS compared to non-ALS differentials. ROC analysis revealed only small area under the curve for detecting ALS (AUC: 0.669 [95%CI: 0.56-0.78]; p = 0.006). Highest Youden index was observed for area size of <0.14 cm2 (Youden index: 0.28). Using this cut-off score and that generated from normative data of healthy controls, area size measurements provided a sensitivity of only 46-58% and specificity of 69-83% for detecting ALS. No correlations of hyperechogenic area sizes in ALS patients were found to age, gender, ALS subtype (bulbar versus spinal form), disease duration or ALS-FRS-R score.ConclusionsMidbrain hyperechogenicity is reproducibly found in ALS patients, but its diagnostic value for discriminating ALS from its key differentials is limited.

Highlights

Hyperechogenicity of the substantia nigra was recently reported in patients with sporadic amyotrophic lateral sclerosis (ALS) with a frequency similar to Parkinson’s disease (PD)
These included subjects with definite or probable ALS according to the revised El Escorial criteria, antibody proven myasthenia gravis (MG), inflammatory neuropathies (IN) (clinical diagnosis according to European Federation of Neurological Societies and the Peripheral Nerve Society (EFNS/PNS) [13,14]) and cervical canal stenosis (CCS)
In subjects with sufficient temporal acoustic bone windows, mean midbrain hyperechogenic areas were significantly higher in ALS compared non ALS patients (P = 0.006; unpaired two-sided t-test:)

Summary

Introduction

Hyperechogenicity of the substantia nigra was recently reported in patients with sporadic ALS with a frequency similar to PD. Data on the diagnostic utility compared to key differential diagnoses of ALS do not exist yet. Transcranial B-mode sonography (TCS) of the midbrain is in the meantime well accepted for the differential diagnosis of Parkinson’s disease (PD) and various movement disorders [1,2,3]. We recently reported a similar high prevalence of hyperechogenecity of the substantia. Post-mortem studies have reported a degeneration of the SN in sporadic ALS [7], which resembles stage 3 of the very recently reported neuropathological classification of Braak and Brettschneider [8,9]. Neuroimaging studies by the use of PET or SPECT have shown abnormal pre-synaptic and post-synaptic striatal dopaminergic function in ALS patients [11,12]

Methods

Results

Conclusion