Constant groaning in PSP (case report)

This recently-published letter to the editor in a medical journal article describes “characteristic constant groaning” in late-stage PSP. The authors, members of a top PSP researcher team in the UK, believe that the constant groaning is “often misinterpreted as due to pain.”

They state:

“We have seen this phenomenon in at least 4 patients in the last two years. All of them presented with constant groaning only when they were in the advanced stages having lost ambulation and being confined to a wheelchair (equal to stage V). This phenomenon is very distressing for their caregivers…”

Indeed, over the last 7 years that I’ve been learning about PSP, many, many caregivers report this symptom of constant groaning on the PSP Forum and elsewhere. Sometimes it’s described as growling, moaning, or humming. I have read many guesses over the years as to why those with PSP do this including clearing the throat, warming up the throat before trying to speak, wanting to stay involved in the conversation, expressing a complaint about something, and comforting oneself.

My father (autopsy-confirmed PSP) had what we called the “moanin’ and groanin” symptom but it was NOT limited to late-stage PSP for him. He groaned for the last 18 months or so of his life. Sometimes it was very loud, and I’d ask him to keep it down a bit; he was able to adjust the volume. Or I’d put my hand back and forth over his mouth so that the sound alternated from loud to muffled; that would make Dad laugh and that stopped the moaning for a short while. Sometimes I’d moan along with him, and found it physically very hard to do for as long as he could do it for. For him, it started as a means of expressing a complaint. Later, it turned into something he did seemingly without a purpose. I’d call him the “ole groaner”; that would get a laugh (when he could laugh).

The authors state:

“[The] groaning in PSP can be seen as analogous to other ‘noise-making’ phenomena which have been described in patients with Alzheimer’s disease, vascular dementia and frontotemporal dementia, such as persistent screaming, perseverative vocalization, continuous chattering, muttering, etc., all together characterized as ‘inappropriate vocalization, due to frontal lobe damage or interruption of subcortical circuits’. What makes this groaning so characteristic of PSP is the combination of the characteristic spastic-hypokinetic dysarthria with perseverative vocalization due to frontal disinhibition…”

I’ve only seen it briefly mentioned in one medical journal article a few years ago (also authored by members of the UK team). Now, this is quite a bit of attention given to one little-discussed symptom.

When I posted this case report on the PSP Forum, the moderator Ed Plowman replied as follows with his experience about his late wife Rose:

Groaning and moaning is common in mid- to late-stage PSP. Rarely does it mean the patient is in pain (but go ahead and ask). It MAY be related to the same kind of progressive nerve damage that results in unintended and uncontrollable-by-the-patient laughter or crying in an earlier stage. Often, my late Rose was unaware of the moaning until I called attention to it; that would seem to get her mind focused elsewhere, and it would stop. I stopped making an issue of it except periodically when I would ask if she was in pain or feeling bad, and in time, that phase of the symptoms went away.

Here’s the citation for the case report, if you’d like to look it up:

Parkinsonism and Related Disorders. 2011 May 13. [Epub ahead of print]

Characteristic constant groaning in late stage progressive supranuclear palsy: A case report.

Stamelou M, Rubio-Agusti I, Quinn N, Bhatia K.
Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, UCL, London, United Kingdom; Department of Neurology, Philipps University, Marburg, Germany.

PubMed ID#: 21571571 (see pubmed.gov for this citation only)

Robin

Hallucinations – rare in PSP and CBD

The authors review the prevalence of and treatment options for hallucinations in Progressive Supranuclear Palsy, Corticobasal Degeneration, and many other disorders. “Overall hallucinations are a rare symptom in PSP and CBD. However, if reported, VH [visual hallucinations] predominate. Questionnaire-based studies found hallucinations in 5–13% in PSP and in 5–21% in CBD. This was echoed by two autopsy-based studies with retrospective chart review where the prevalence was 7% for PSP and 0% for CBD.”

The authors argue that because of the need for treatment, “the distinction of disease-inherent hallucinations from medication-associated perceptual disturbances is highly relevant.” This article addressed medication-associated hallucinations along with delirium-associated hallucinations and surgery-associated hallucinations. Both delirium- and surgery-associated hallucinations may be due to medication as well.

I’ve copied the abstract of the article below.

Robin

CNS Neuroscience & Therapeutics. 2011 Feb 16. [Epub ahead of print]

Hallucinations in Neurodegenerative Diseases.

Burghaus L, Eggers C, Timmermann L, Fink GR, Diederich NJ.
Department of Neurology, University of Cologne, Cologne, Germany Cognitive Neurology Section, Institute of Neurosciences and Medicine (INM3), Research Center Jülich, Jülich, Germany Department of Neurology, Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg.

Abstract
Background: Patients with neurodegenerative disease frequently experience hallucinations and illusionary perceptions. As early symptoms, hallucinations may even have diagnostic relevance (i.e., for the diagnosis of Lewy Body Dementia).

In the later course of the disease, hallucinations may appear as characteristic symptoms and often constitute a particular challenge for therapeutic endeavors.

Here, the distinction of disease-inherent hallucinations from medication-associated perceptual disturbances is particularly relevant.

Results: Synucleinopathies and tauopathies have different risk profiles for hallucinations. In synucleinopathies hallucinations are much more frequent and phenomenology is characterized by visual, short-lived hallucinations, with insight preserved for a long time. A “double hit” theory proposes that dysfunctionality of both associative visual areas and changes of limbic areas or the ventral striatum are required.

In contrast, in tauopathies the hallucinations are more rare and mostly embedded in confusional states with agitation and with poorly defined or rapidly changing paranoia. The occurrence of hallucinations has even been proposed as an exclusion criterion for tauopathies with Parkinsonian features such as progressive supranuclear palsy.

Conclusion: To date, treatment remains largely empirical, except the use of clozapine and cholinesterase inhibitors in synucleinopathies, which is evidence-based. The risk of increased neuroleptic sensitivity further restricts the treatment options in patients with Lewy Body Dementia. Coping Strategies and improvement of visual acuity and sleep quality may be useful therapeutic complements.

© 2011 Blackwell Publishing Ltd.

PubMed ID#: 21592320 (see pubmed.gov for this abstract only)

Quality of Life in PSP – Lower in Women, Depressed, etc/

This is a *very* interesting article on quality of life in PSP and MSA. The research team is one of the top in the world studying PSP. (They are not as well known for their MSA research.)

The researchers use the term health-related quality of life (HrQoL). This term “describes different aspects of self-perceived well-being which are affected by…disease and its treatment.” “HrQoL is an important aspect in the healthcare of chronic diseases such as neurodegenerative disorders.”

Study participants completed a generic HrQoL instrument, the EQ-5D; this instrument has been validated for use in parkinsonian disorders. “The EQ-5D comprises five questions that relate to five dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is divided into three levels of severity (1 = no problem, 2 = moderate problem, 3 = severe problem). … The study participants also rated their current HrQoL on a visual analogue scale (VAS thermometer type) ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).”

One hundred and one German patients were initially recruited. Some patients were excluded. In the end, 86 patients completed the study — 18 MSA-C, 28 MSA-P, and 40 PSP.

The researchers found:

* Factors of reduced HrQoL were “female gender, <12 years of education, disease severity, a decreased number of persons in the household and depression.”

Regarding education, the authors note: “This may reflect insight and expectations of patients, which are known to have influence on quality of life in other chronic diseases.” And, the authors state: “educational programs on APS could contribute to improvement of HrQoL in these diseases.”

Disease severity was measured by the UMSARS IV (Unified MSA Rating Scale, part IV), even in the PSP patients. Depression was measured by the BDI (Beck Depression Inventory).

The authors argue that greater attention needs to be paid to the treatment of depression. Perhaps this conclusion was drawn because only 80% of the depressed patients were receiving adequate antidepressant therapy.

* “With increasing disease severity, the proportion of married patients decreased and the proportion of divorced patients rose.”

* “The dimensions [on the EQ-5D] most affected were ‘selfcare’ and ‘usual activities’. Severe problems in these dimensions were reported by 38.4 and 57.0% of the patients, respectively.”

* “[Pain] was more problematic in MSA than in PSP…”

I’ve copied the abstract below.

Robin

Neurodegenerative Diseases. 2011 May 12. [Epub ahead of print]

Health-Related Quality of Life in Multiple System Atrophy and Progressive Supranuclear Palsy.

Winter Y, Spottke AE, Stamelou M, Cabanel N, Eggert K, Höglinger GU, Sixel-Doering F, Herting B, Klockgether T, Reichmann H, Oertel WH, Dodel R.
Department of Neurology, Philipps University Marburg, Marburg, Germany.

Abstract
Objective: Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), known as atypical parkinsonian syndromes (APS), are neurodegenerative disorders with severe disability and decreased life expectancy.

Little is known about the health-related quality of life (HrQoL) and its determinants in patients with those disorders. The objective of our cross-sectional study was to evaluate the HrQoL in patients with APS and to identify the determinants of HrQoL.

Methods: A total of 101 consecutive patients with MSA (n = 54) and PSP (n = 47) were recruited in four German neurological centers.

Disease severity was assessed using the Hoehn and Yahr stages and the Unified MSA Rating Scale.

The HrQoL was evaluated using the EuroQol instrument (EQ-5D and EQ-VAS). Independent determinants of HrQoL were identified in multiple regression analyses.

Results: The mean EQ-VAS score was 52% lower than that reported for the general population (36.9 ± 18.3 vs. 77.4 ± 19.0).

Of the study participants, 63% reported severe problems in at least one dimension of the EQ-5D.

Cerebellar dysfunction was associated with a more considerable reduction of HrQoL.

Independent determinants of reduced HrQoL were female gender, <12 years of education, disease severity, a decreased number of persons in the household and depression.

Conclusions: The HrQoL in MSA and PSP is considerably reduced. While therapeutic options in the treatment of motor symptoms remain restricted, greater attention should be paid to the treatment of depression, which was identified among independent determinants of HrQoL. Independent determinants of HrQoL should be considered when developing healthcare programs aimed at improving the HrQoL in APS.

Copyright © 2011 S. Karger AG, Basel.

PubMed ID#: 21576919 (see pubmed.gov for this abstract only)

“New insights” into PSP

This recently-published paper is about “new insights” into atypical parkinsonism, including MSA, DLB, PSP, and CBD. The paper is based upon medical journal articles published in 2010. Two of the three authors are well-known Austrian researchers in the atypical parkinsonism community.

The authors describe atypical parkinsonian disorders (APDs) as “characterized by relentlessly progressive and levodopa refractory parkinsonism associated with a range of distinctive atypical features.”

Here are the key points made in the article related to PSP:

* “During the last years, infrequent variants due to PSP tau pathology have been separated from the ‘classical’ syndrome (Richardson syndrome). These variants that challenge the concept of clinicopathologic PSP include PSP-parkinsonism (PSP-P), pure akinesia with gait freezing (PAGF), corticobasal syndrome (CBS), and progressive nonfluent aphasia. … The regional differences in pathological severity almost certainly account for the clinical differences and logically correlate with the different clinical features.”

* “Familial PSP is rare and sometimes related to familial frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17).”

* “Male sex, older age at disease-onset and higher PSP rating scale scores were independent predictors of shorter survival.”

* “A natural history study confirmed previous observations of high levels of cognitive impairment associated with PSP occurring in up to 50% of patients at early disease stages. Furthermore, the cognitive profile characterized by frontal-executive dysfunction was similar to a control cohort of patients with MSA.”

* “The NINDS-SPSP (National Institute of Neurological Disorders­Society for Progressive Supranuclear Palsy) criteria were established 15 years ago focusing on the classic Richardson syndrome presentation.”

Copied below is the abstract.

Robin

Current Opinion in Neurology. 2011 May 13. [Epub ahead of print]

New insights into atypical parkinsonism.

Wenning GK, Krismer F, Poewe W.
Department of Neurology, Medical University, Innsbruck, Austria.

Abstract

PURPOSE OF REVIEW:
Atypical parkinsonian disorders (APDs) comprise a heterogenous group of disorders including multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Based on literature published in 2010, we here review recent advances in the APD field.

RECENT FINDINGS:
Genome-wide association studies have provided robust evidence of increased disease risk conferred by synuclein and tau gene variants in MSA and PSP. Furthermore, advanced imaging tools have been established in the differential diagnosis and as surrogate markers of disease activity in patients with APDs. Finally, although therapeutic options are still disappointing, translational research into disease-modifying strategies has accelerated with the increasing availability of transgenic animal models, particularly for MSA.

SUMMARY:
Remarkable progress has been achieved in the field of APDs, and advances in the genetics, molecular biology and neuroimaging of these disorders will continue to facilitate intensified clinical trial activity.

PubMed ID#: 21577106 (see pubmed.gov for this abstract only)

“New insights” into CBD

This recently-published paper is about “new insights” into atypical parkinsonism, including MSA, DLB, PSP, and CBD. The paper is based upon medical journal articles published in 2010. Two of the three authors are well-known Austrian researchers in the atypical parkinsonism community.

The authors describe atypical parkinsonian disorders (APDs) as “characterized by relentlessly progressive and levodopa refractory parkinsonism associated with a range of distinctive atypical features.”

Here are the key points made in the article related to CBD:

* “The clinical presentation of CBD is variable and includes the CBS, PSP, progressive aphasia, and frontotemporal dementia. However, CBD research is hampered by the rarity of the disorder, patients being scattered over a large geographic area.”

* “A recent clinicopathological study showed that only the minority of postmortem confirmed CBD cases were diagnosed correctly in life (five out of 19 cases) and that the clinical syndrome of CBS is not specific for CBD. Intriguingly, most of the pathologically confirmed CBD cases were characterized clinically by a PSP-like presentation with delayed onset of vertical supranuclear gaze palsy.”

* “Intriguingly, an Alzheimer’s disease-like CSF pattern was associated with early memory decline in patients with CBS according to a recent study.”

Copied below is the abstract.

Robin

Current Opinion in Neurology. 2011 May 13. [Epub ahead of print]

New insights into atypical parkinsonism.

Wenning GK, Krismer F, Poewe W.
Department of Neurology, Medical University, Innsbruck, Austria.

Abstract

PURPOSE OF REVIEW:
Atypical parkinsonian disorders (APDs) comprise a heterogenous group of disorders including multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Based on literature published in 2010, we here review recent advances in the APD field.

RECENT FINDINGS:
Genome-wide association studies have provided robust evidence of increased disease risk conferred by synuclein and tau gene variants in MSA and PSP. Furthermore, advanced imaging tools have been established in the differential diagnosis and as surrogate markers of disease activity in patients with APDs. Finally, although therapeutic options are still disappointing, translational research into disease-modifying strategies has accelerated with the increasing availability of transgenic animal models, particularly for MSA.

SUMMARY:
Remarkable progress has been achieved in the field of APDs, and advances in the genetics, molecular biology and neuroimaging of these disorders will continue to facilitate intensified clinical trial activity.

PubMed ID#: 21577106 (see pubmed.gov for this abstract only)