Bulbar-onset ALS Diagnosed in Man with PNFA, Type of Frontotemporal Dementia

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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A man with progressive non-fluent aphasia (PNFA), one of the three types of frontotemporal dementia (FTD), was unusual in developing amyotrophic lateral sclerosis (ALS) with bulbar-onset one year later, a case study from Italy reports.

The study, “A case of Progressive Non-Fluent Aphasia as onset of Amyotrophic Lateral Sclerosis with FrontoTemporal Dementia,” was published in the International Journal of Neuroscience.

FTD comprises a group of disorders that affect the working of the frontal and temporal lobes of the brain – brain areas typically associated with personality, language and behavior.

A link between ALS and FTD is well-established, and case studies document a strong association between ALS and the behavioral form of FTD. Indeed, approximately 12–14% of patients with behavioral FTD develop ALS at some point in the course of this disease.

FTD-ALS is marked by the behavioral and language impairments typically associated with behavioral FTD and the progressive muscle weakness characteristic of ALS. At onset, patients may experience symptoms associated with either FTD or ALS, and develop symptoms marking both as illness progresses.

But the link between ALS and pure semantic dementia (SD) or progressive non-fluent aphasia (PNFA) — the two other types of FTD — is extremely rare, with an incidence of 1 to 3%. Since the diagnostic criteria for PNFA was updated in 2011, no clinical cases have been reported.

A team of researchers in Novara, Italy, treated a patient diagnosed with PNFA who developed bulbar-onset ALS one year after the initial diagnosis. (Bulbar-onset is marked by first symptoms involving the head and neck, including trouble speaking or swallowing; more common is limb-onset ALS.)

The man, a 60-year-old Caucasian, began to report difficulties in spontaneous speech, in particular articulating sentences, words and sounds, in November 2015.

Magnetic resonance imaging (MRI) revealed a mild atrophy in the left temporal lobe of the patient’s brain. His problems with language continued to worsened substantially, and he was diagnosed with PNFA six months later.

He began experiencing symptoms associated with ALS, including difficulty swallowing, breathing, speaking, and muscle twitching/weakness in the neck, tongue and limbs in December 2016.

A diagnosis of sporadic ALS with bulbar onset, following guidelines defined by the El Escorial Criteria, was given in January 2017.

The man’s clinical state rapidly deteriorated and one month later, he underwent non-invasive ventilation to ease breathing difficulties. He died of respiratory failure about a year later.

Screening for key genes linked to motor neuron disease and dementia were done over the course of his treatment, but no genetic variants associated with related disorders were found.

“The rarity of the association between PNFA and ALS may depend on neurobiological reasons. Another possible explanation is related to the neuropsychological characterization of the language deficit, whose progression could be confounded by a motor disorder,” the scientists wrote.

“Further studies on large series are needed to better stratify patients regarding clinical characterization and prognosis of the complex FTD-ALS,” they concluded.