Progressive supranuclear palsy

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Classification according to ICD-10
G23.1 Progressive supranuclear ophthalmoplegia
(Steele-Richardson-Olszewski syndrome)
ICD-10 online (WHO version 2019)
Brain slices in a patient with PSP
This patient was presented with progressive dementia, ataxia, and incontinence. The clinical diagnosis of normal pressure hydrocephalus could not be confirmed by imaging. The eye examination revealed nystagmus and abnormal eye movements. Magnetic resonance imaging (T1-weighted) shows atrophy of the midbrain, with preservation of the volume of the cerebellar stalks, and atrophy of the midbrain dome, especially the superior colliculi . These results suggest progressive supranuclear palsy.

The progressive supranuclear palsy ( progressive supranuclear nuclear palsy , PSP , and progressive supranuclear palsy , Steele-Richardson-Olszewski syndrome ) is a degenerative disease of the brain , especially the basal ganglia . The basal ganglia are areas in the brain that play an important role in controlling automatic movement. Their damage can lead to problems with moving and maintaining balance, with eye control, swallowing control and speech control. PSP is related to Parkinson's disease , the diseases are similar in many symptoms. It is not uncommon for the less common PSP to be mistaken for Parkinson's disease. PSP is combined with other Parkinson's-like diseases under the term atypical Parkinson's syndromes or Parkinson-plus .

history

Progressive supranuclear palsy (PSP) was first described in 1964 by John Steele, Clifford Richardson, and Jerzy Olszewski. The neurologist Richardson had been consulted by a friend who complained of clumsiness, problems with vision, and easy forgetfulness. Richardson watched the disease progress and discovered similar symptoms in other patients. Olszewski and Steele, also physicians, had examined the lesions that they discovered in the brains of deceased patients with comparable symptoms.

distribution

PSP is a rare disease. Even so, it is the second most common movement disorder after Parkinson's disease. It is estimated that six to seven out of 100,000 people will develop PSP at some point in their lives (compared to Parkinson's disease: 100 to 200 out of 100,000).

Symptoms

The symptoms of PSP can be very different, they appear in a varying order and become increasingly stronger ( progressive course ) - but symptoms can also be absent entirely. Pointing out a PSP:

  • Increasing difficulties in moving the eyes, slowed saccades , vertical palsy of the gaze upwards, gaze usually lowered or head tucked back, diplopia , blurred vision, which cannot be reliably objectified
  • Tendency to fall backwards and unsteady gait
  • Speech problems: increasingly difficult to understand, quiet
  • Onset of the disease in the second half of life
  • subcortical dementia

In contrast to the related Parkinson's disease, the usual tremor or shaking of arms and legs (tremor) is rarely observed in PSP.

causes

The causes were unknown to Steele, Richardson, and Olszewski in 1964. Even today little is known about the causes of PSP. Three genetic defects are known, one in the gene coding for the tau protein , which can trigger PSP.
PSP is a tauopathy, a disease in which the protein tau clumps together instead of stabilizing the cell structure. Affected nerve cells die. Diseased cells are repaired or broken down. The protein PERK (Protein Kinase RNA-like Endoplasmic Reticulum Kinase) as part of this maintenance system is defective in PSP. It reacts - with the protein kinase Ire1 (Inositol-requiring Enzyme 1) and the transcription factor ATF6 (Activating Transcription Factor 6) - to a protein misfolding in the form of an Unfolded_Protein_Response .
PSP symptoms decrease when PERK is activated with pharmaceuticals, i.e. the effect of PERK is increased. PERK helps eliminate faulty tau molecules. These also occur in other brain diseases.

As far as the other cases are concerned, it is assumed that a toxic substance ( neurotoxin ) can sometimes trigger PSP with a genetic predisposition , since PSP-like diseases occurred more frequently on the islands of Guam (here Lytico-Bodig ) and Guadeloupe . It is suspected that substances occurring on both islands are the cause of the disease. Alternative hypotheses go e.g. B. from an infection with previously unknown viruses.

Treatment and course

The PSP is so far not curable. The symptomatic treatment with L-Dopa , which is typical for Parkinson's disease and relieves symptoms there, has only a short or no effect on PSP. So far, no approved drug has been shown to have a clearly positive effect on the course or symptoms of PSP.
Physiotherapy (balance training, gait training), occupational therapy (fine motor skills training, use of aids ...) and speech therapy are important in the treatment of PSP.

The mean survival time after the onset of symptoms is 5.6 (2–16.6) years. Unfavorable prognostic factors are: older age at the onset of the disease, onset of falls in the first year, early dysphagia. Pneumonia caused by swallowing problems ( aspiration pneumonia ), falls and infections are among the most common causes of death.

Web links

literature

Individual evidence

  1. ↑ A. Magherini, I. Litvan: Cognitive and behavioral aspects of PSP since Steele, Richardson and Olszewski's description of PSP 40 years ago and Albert's delineation of the subcortical dementia 30 years ago. In: Neurocase. Vol. 11, No. 4, 2005, pp. 250-262, doi : 10.1080 / 13554790590962979 .
  2. ^ Martin L. Albert, Robert G. Feldman, Anne L. Willis: The "subcortical dementia" of progressive supranuclear palsy. In: Journal of Neurology, Neurosurgery and Psychiatry. Vol. 37, No. 2, 1974, pp. 121-130, doi : 10.1136 / jnnp.37.2.121 .
  3. ↑ PSP.  In: Online Mendelian Inheritance in Man . (English).
  4. ↑ Julius Bruch, Hong Xu, Thomas Rösler, Ulrich Müller, Günter Höglinger et al .: PERK activation mitigates tau pathology in vitro and in vivo. In: EMBO Molecular Medicine. doi : 10.15252 / emmm.201606664 .