Tag Archives: facio-scapulo-humeral dystrophy

Know our enemy

Posted on by

Here are the last 3 of the 7 research posters on clinical features of PSP from the Movement Disorder Society’s August 2023 meeting in Copenhagen. My editorial comments in italics.

Narcolepsy type 1, supranuclear vertical gaze palsy, and agrypnia excitata in a patient with anti-Ma associated encephalitis.

C. Espinoza-Vinces, A. Horrillo, R. Villino, A. Solis, P. Domínguez, J. Arbizu, MR. Luquin, E. Urrestarazu, I. Avilés-Olmos (Pamplona, Spain)

Ma is a normal protein located in the parts of the brain serving vertical gaze, sleep, memory, personality, and motor control.  The immune system can make antibodies against Ma, usually in the process of fighting off a cancer that contains that protein or sometimes for no apparent reason.  The result is usually one of severe cognitive/behavioral changes or cerebellar ataxia but can occasionally mimic PSP.  This poster is such a case report in of a 53-year-old man with a 3-year diagnosis of narcolepsy who then rapidly developed features of PSP.  His spinal fluid and MRI were diagnostic of encephalitis.  The authors caution physicians that in patients with apparent PSP presenting with important sleep problems, to consider anti-Ma encephalitis.  That condition may respond to steroids or to removal of an underlying tumor. 

Anti-Ma encephalitis is one of the 52 disorders listed in the guide to the differential diagnosis of PSP that a working group of CurePSP Centers of Care is about to submit for publication.  Neurologists have long known it as a potential but rare cause of cerebellar ataxia but should also consider it in someone with apparent PSP that develops rapidly or at a relatively early age.

Atypical progression of motor symptoms in facio-scapulo-humeral dystrophy: clinical worsening or overlap?

D. Calisi, M. de Rosa, M. Russo, A. Thomas, M. Onofrj, S. Sensi (Chieti, Italy)

Facio-scapulo-humeral dystrophy, unlike most other kinds of muscular dystrophy, can start at any age and allow many decades of survival.  This case report describes a man in his 60s with FSHD since childhood confirmed on muscle biopsy and genetic testing.  The typical weakness in his face, neck, shoulders and upper arms progressed very slowly until he started to show slowness, vertical gaze palsy, falls, freezing and dysphagia.  His symptoms were attributed to the FSHD until imaging proved consistent with PSP.  The authors’ caution physicians that the diagnosis of PSP can be missed for years when it develops in the context of an unrelated, progressive motor disorder.

While the previous poster, on anti-Ma encephalitis mimicking PSP, is an example of a false positive, this one is a false negative.  These are excellent teaching cases for neurology residents.  I always taught my students and residents to consider concomitant neurological diagnoses and diagnostic mimics at each follow-up visit with a patient with a chronic disease, no matter how routine the visit was expected to be.

Prognostic impact of frontal-lobe clinical bedside signs in progressive supranuclear palsy

Ruiz Barrio, A. Horta Barba, S. Martinez Horta, J. Kulisevsky, J. Pagonabarraga (Barcelona, Spain)

These researchers tabulated frontal lobe signs in 61 people with PSP and compared those results with overall disability in the form of PSP Rating Scale total score.  (Problems with the frontal lobe explain the common PSP symptoms of loss of inhibition, repetition of words or movement, grasping, and many others.)  They found that grasping, orobuccal apraxia (inability to coordinate movements of the muscles around the mouth), and anosognosia (loss of awareness of illness) each correlated with PSPRS score independent of other neurological or demographic features.  In a sub-analysis of 51 patients evaluated during the first 4.3 years of the disease, groping was found to be an independent risk factor for shorter eventual survival.

Such observations can be highly variable across studies, but if confirmed, data like this could allow more rational analysis of neuroprotection drug trial outcomes and could also assist in patient and family counseling.

Next post on MDS conference posters:  Two science-nerdy ones on what’s working wrong in the brain in PSP.

Five complicated pieces – part 1

Posted on by

Every day I search PubMed on the term “progressive supranuclear palsy.”  In fact, the PubMed bookmark on my browser is set to that search term as the default.  I’m used to seeing about three new articles appear per week, but over the past 10 days or so, nothing. 

But today, just as I was I wondering if some human being critical to this process at the National Library of Medicine had been downsized, five new articles appeared, and they’re all pretty interesting.  To celebrate the event, I thought I’d share elevator explanations of each, starting here with the first two:

—–

G. Meduri et al. / FKBP52 Decrease is an Early Feature of Different Tauopathies

A group at France’s equivalent of the NIH (called “INSERM”) discovered in 2010 that a protein called FKBP52 plays a role in the normal degradation of the tau protein.  Now, (links: abstract; full pdf) some of those same researchers have found that levels of FKBP52 are reduced in the brain cells with highest levels of abnormal tau.  They used mouse models and also frontal cortex brain tissue from autopsies showing Alzheimer’s, familial frontotemporal lobar degeneration, Pick’s disease, corticobasal degeneration and PSP.

Furthermore, they found those reduced levels even before any damage had taken place.  This suggests that the direction of causation proceeded from reduced FKBP52 to excessive tau to brain cell damage.  This in turn suggests that a hypothetical imaging procedure showing FKBP52 in the brain could serve as a pre-symptomatic or very early-stage diagnostic test.

The most important implication of this insight is that increasing FKBP52 production (or slowing its rate of loss) could prevent, slow or halt the disease process.  Just as important, it found the same thing in all of those tauopathies, suggesting that they could share the same treatment.

All the more reason for researchers and drug companies interested in Alzheimer’s disease to start out by looking at PSP, which for several reasons is easier to do research on.

—–

Calisi D et al / Case report of FSH dystrophy Obscuring PSP

Facio-scapulo-humeral dystrophy (FSHD) is a common form of slowly-progressive muscular dystrophy that can start anywhere from childhood to late middle age.  It can eventually cause major disability, but does not shorten lifespan or affect cognition or behavior.

Neurologists in Chieti, Italy report a man in his early 60s with FSHD since childhood confirmed by genetic testing and muscle biopsy.  (Here’s the abstract.) About 5 years before, he had begun to develop more general difficulty with movement that progressed rapidly.  It was diagnosed as atypically rapid progression of FSHD until a neurologist noticed specific signs of PSP that do not occur in FSHD such as vertical gaze palsy, rigidity in the neck, trouble swallowing liquids, impairment of “executive” cognitive abilities and compulsive behavior.  Brain MRI showed atrophy of the midbrain, as is typical for PSP. 

The point is that while PSP is not currently curable, receiving an accurate diagnosis can help in one’s residential, healthcare and financial planning, avoid useless diagnostic tests and treatments, and allow participation in clinical trials.  Once we have a way to slow or halt the progression, an accurate diagnosis could be lifesaving. 

Thanks to this modest case report, physicians taking care of people with FSHD and other chronic, relatively benign disorders affecting movement now know to consider a second diagnosis of PSP in someone with an unusual rapid progression and new neurological features related to the brainstem and frontal lobes.