Primary Lateral Sclerosis: Clinical Features, Neuropathology and Diagnostic Criteria

Abstract

Eight patients with a homogeneous syndrome of progressive symmetric spinobulbar spasticity were studied. Clinical features were limited to those associated with dysfunction of the descending motor tracts and included spastic quadriparesis, pseudobulbar affect, spastic dysarthria, hyper-reflexia and bilateral Babinski signs. Lower motor neuron findings were absent and higher cognitive function preserved. Median age of onset was 50.5 yrs and median disease duration was 19 yrs. Neuropathologic features (including morphometric analysis) in the single autopsied case confirmed the selective involvement of the motor cortex. There was complete absence of Betz cells from layer 5 of the precentral cortex and the remaining pyramidal cells were significantly smaller than those seen in normal controls. Magnetic resonance imaging (MRI) revealed atrophy of the precentral gyrus and positron emission tomography (PET) scans showed diminished glucose [18F]fluorodeoxyglucose uptake in the pericentral cortex. Magnetic motor cortex stimulation revealed markedly prolonged central motor conduction times. The literature is reviewed and diagnostic criteria for primary lateral sclerosis based on clinical, laboratory and imaging features are proposed.

Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis

“…It is now understood to have multiple aetiologies [Turner and Swash, 2015] and shares clinical, pathological, and genetic overlap with frontotemporal dementia (FTD) [Phukan et al, 2012]. The term primary lateral sclerosis (PLS) encompasses a very slowly progressive phenotype with pure upper motor neuron (UMN) degeneration [Pringle et al, 1992]. The improved characterization of the genetic substrate for familial ALS now enables the study of asymptomatic mutation carriers predisposed to developing ALS [Benatar et al, 2013].…”

Prospective Validation of 18F-FDG Brain PET Discriminant Analysis Methods in the Diagnosis of Amyotrophic Lateral Sclerosis

“…In patients with ALS, a pattern of relative hypometabolism in the primary motor cortex, premotor cortices, and supplementary motor cortex but extending to extramotor areas such as the frontal and parietal lobes as well has been observed (2,4,(7)(8)(9)(10)(11). Relative hypermetabolism is observed in the mesotemporal cortex, cerebellum, and upper brain stem (2,4,7,10,(12)(13)(14).…”

Seipin/BSCL2 mutation screening in sporadic adult-onset upper motor neuron syndromes

“…In families with the seipin/BSCL2 mutation, the frequency of an HSP phenotype has been observed to be as high as 10% of patients [1]. The other 46 patients in our study had symptomatic UMN involvement of the arms or bulbar region, which may suggest a diagnosis of PLS [6,10]. The results of our study indicate that the seipin/BSCL2 exon 3 mutations are not a common cause of sporadic pure HSP and PLS.…”

“…Primary lateral scherosis is a sporadic disorder of progressive spino-bulbar spasticity and may be part of the clinical spectrum of amyotrophic lateral sclerosis (ALS) [10]. Hereditary spastic paraparesis is a clinically and genetically heterogeneous group of disorders characterized by a slowly progressive spastic paraparesis [8,12].…”