Progressive Supranuclear Palsy (PSP)

— JULY 2012 289Indian Medical Gazette

Case Report

Addr ess for correspondence: Dr Sourya Acharya, Associate Professor, Dept. of Medicine, J. N. Medical College, A. V. B. R. Hospital, Sawangi(Meghe), Wardha - 442 004, Maharashtra. E-mail: [email protected]

Progressive Supranuclear Palsy (PSP)

Dinesh Singh, Resident,

Amit Gupta , Resident,

Sourya Acharya, Associate Professor,

S. K. Diwan, Professor,

S. N. Mahajan, Professor & H.O. D.

— Dept. of Medicine, DMIMSU, Wardha

Abstract

We present 2 cases of Progressive supranuclear palsy(PSP), both of the cases presented to us with typical signsof Parkinson’s disease (PD), but they also had history offalls and difficulty in looking downwards. PSP is one ofthe variants of Parkinson Plus Syndromes.

Keywords

PSP, Parkinson’s disease

Introduction

Charles Dickens may have been the first to describe asubject with classical PSP in 1857 in his novel The LazyTour of Two Idle Apprentices1: “A chilled, slow, earthy,fixed old man. A cadaverous man of measured speech. Anold man who seemed as unable to wink, as if his eyelidshad been nailed to his forehead. An old man whose eyes -two spots of fire - had no more motion that [sic] if theyhad been connected with the back of his skull by screwsdriven through it, and riveted and bolted outside, amonghis grey hair.” He did not bend himself to sit, as other peopledo, but seemed to sink bolt upright, as if in water, until thechair stopped him.”

Progressive supranuclear palsy (PSP) is a

neurodegenerative disease that affects the basal ganglia andthe brainstem. The cardinal features of PSP being;

It is associated with deposition of hyperphosphorylatedtau proteins as neurofibrillary tangles in the basal gangliaand brainstem.(3,4)This entity is often underdiagnosed/misdiagnosed as primary Parkinson’s disease due to a fewoverlapping clinical features. Its diagnosis becomesstraightforward once it is considered by the clinician dueto a few distinctive clinical features of brainsteminvolvement. Its diagnosis is of utmost importance becausetheir prognosis and response to treatment differs enormouslyfrom Primary Parkinson’s disease.

Case Report

First patient was a 70 year old female who was broughtby relatives with a h/o breathlessness and cough withexpectoration since 10 days. She was diagnosed as right

290 — JULY 2012Indian Medical Gazette

lower lobe pneumonia. On detailed history she revealed ahistory of frequent retropulsion falls in the last nine months,dysphagia with dysarthria. She was diagnosed as a case ofPD 4 months back and was on Tab .L-Dopa, Tab.Pramipexole and Tab. Seligelline since 4 months. Butaccording to the relatives her condition had remained thesame over the last 4 months. On neurological examinationwe found a typical Parkinson’s facies, with less frequentblinking and a widening of the eyelid in a “surprised” look(Fig. 1). Vertical optical movement was decreased,especially downward gazes, while horizontal opticalmovements were normal. Axial rigidity was obvious. Deepreflexes were normal and the cetaneous plantar responseswere flexor. Some frontal signs were present, affectingthe glabella, as well as the jaw and palmate nerves. Thepatient did not have tremors. The rest of the physicalexamination was normal. The computerized axialtomography (CAT) scan confirmed cortical, subcortical andcerebellar atrophy. The diagnosis was revised to PSP.

The second patient was an 80-year old male patient whopresented with complaints of dysarthria and difficulty inwalking due to episodes of frequent falls since the last 1year. On clinical examination he had no orthostatichypotension. On neurological examination he had reducedblinking with a staring look and downward gaze palsy

(Figs. 2,3). Axial rigidity was present. Deep reflexes werenormal with a flexor plantar response. However tremorsand cogwheel rigidity were absent. We started the patienton L-Dopa and Tab. Seligelline. But he did not show anysignificant response even after 1 month of treatment. CTscan of the brain revealed diffuse cerebral atrophy. Thediagnosis was once again kept as PSP.

These 2 cases were quite similar in their clinical profile.

Fig. 1Showing staring look with downward gaze palsy

Fig. 2Showing downward gaze palsy

Fig. 3Showing normal lateral gaze


The most prominent features which made us think of PSPinstead of PD despite the fact that both patients hadParkinsonian features were the complaints of frequent fall/postural instability, supranuclear gaze palsy, dysarthria, tautfacial appearance, axial rigidity with lack of response todopaminergic drugs and absence of rigidity and tremors.

Discussion

Parkinson Plus Syndromes

We use the term parkinson-plus to refer to aheterogeneous group of diseases that present as aparkinsonian syndrome (different from primary Parkinson’sdisease), associated with other neurological symptoms. Thisdisease group represents approximately 15% ofconsultations referred to specialized neurological clinics2.

The diseases included under this heading are,

standard anti-Parkinson treatments2. Therefore diagnosingthese conditions is a must and a high degree of clinicalsuspicion is required for diagnosing these Parkinson Plussyndromes.

A few clues helpful in diagnosis are;

It is important to distinguish various forms of ParkinsonPlus syndromes from Primary PD. The following tablestates a few clinical differences between Primary PD andPSP

Progressive Supranuclear Palsy

Steele, Richardson and Olsweski described the disease,also known as the Steele-Richardson disease, for the firsttime in 19647. It is the most frequent cause of parkinson-plus, representing 6% to 12% of parkinsonian cases referredto tertiary centres. It is estimated that the prevalence amongthe general population is about 1% of that of Parkinson’sdisease — a prevalence that is probably underestimated inthe sub-diagnosis7.

Clinical Features

1) Ocular Features(9,2) :- Ophthalmoplegia is animportant characteristic of this disease. It may be absent atthe onset of the disease, making the diagnosis more difficult.Vertical gaze palsy, especially of downward optical

Patients with Parkinson-plus syndromes typically havea worse prognosis than those with Parkinson’s Disease,and Parkinson-plus syndrome responds poorly to the


movements, is a distinctive feature of this disorder. As thedisease progresses, horizontal optical movements may beaffected, although much less than the vertical opticalmovements. This is a type of supranuclear ophthalmoplegia,meaning that the voluntary movements are absent, but thereflex movements of the head are preserved. Patients maypresent with numerous other ocular impairments, namelyfailure of convergence and failure of ocular fixation withsquare-wave jerks, abnormal optokinetic nystagmus, as wellas an inadequate suppression of the vertical vestibulo-ocularreflex. Frontalis overactivity with a blink rate of <4/minlead to “surprised look” appearance of the face. Apraxia ofeyelid opening or closure may also be present, as well asblepharospasm.

2) Rigidity(9,2):- It typically affects axial movementsrather than the limbs, as observed in Parkinson’s disease.

Orthostatic hypotension develops, the gait accelerates andpatients have difficulty turning, “spinning” rather than takingfirm steps, which increases their risk of falling, especiallybackwards (retropulsion). Parkinsonian syndromes are oftensymmetrical, which differs from the majority of primaryParkinson’s disease cases. Another peculiarity of PSP iscervical and facial dystonia, in particular, retrocollis in theadvanced stages of the disease. The face takes on a lookthat emphasizes wrinkles, rigidity and enlargement of theeyelids. Patients tend to have a “poker-faced” expression.

3) Other features(9,2):- The patient may also presentwith cortico-bulbar and cortico- spinal impairments withhyperreflexia and Babinski’s sign, as well as with apseudobulbar syndrome.Tremors are distinctly uncommon.Dysphagia and dysarthria are common. Patients’ speech ismonotonous, spastic and hyper-nasal. They may makesounds involuntarily. There is a higher incidence of dementia– especially in cases of frontal dementia among PSPpatients.

Pathology

1) PSP is characterised by deposition of neurofibrillarytangles histochemically positive for tau and negative foramyloid or alfa-synuclein.

2) Varying degree of degeneration in brainstem,basalganglia and cerebellum.

3) There is a loss of dopamine and dopamine receptorsdue to intrinsic striatal damage which accounts for poorresponse to therapy.

Neuro Imaging Findings(10,11)

1) MRI brain:-

Midbrain atrophy (superior colliculi).

Criteria used for the diagnosis of PSP included midbraindiameter on axial scans of less than 17 mm, signal increasein the midbrain, atrophy or signal increase of the red nucleusand signal increase in the globus pallidus.

2) PET scan:- Impairment of the cortex, as well asfrontal hypometabolism. The metabolism of the putamensand caudate nucleus slows down.

3) EEG:-Non specified abnormalities.


Treatment(12,13,14)

1) Supportive treatment is the mainstay of therapy.

2) Physiotherapy and occupational therapy formaintenance of balance and prevention of falls.

3) Speech therapy and appropriate measures toprevent complications like aspiration due to swallowingdifficulties.

4) Amantadine has modest benefit in improving motordeficits of PSP.

5) Patients do not respond well to dopaminergicagents.

6) Cholinergic agonists like physostigmine may betried taking into consideration their cardiovascular sideeffects.

7) Novel therapies:-

a. Botulinum toxin for dystonia and blepharospasm.

b. Coenzyme Q10:- a physiological co-factor ofmitochondrial complex I, was associated with anincreased ratio of high-energy phosphates to low-energy phosphates. The PSP rating scale and FrontalAssessment Battery also improved slightly butsignificantly with CoQ10 treatment compared toplacebo.

Conclusion

Idiopathic Parkinson’s disease presents a vast array ofdifferential diagnoses. The Parkinson plus group of diseasesis an important component. This group of diseases is oftennot diagnosed because of its heterogeneity, its subtle clinical


signs and the failure to recognize it. Nonetheless, it isimportant to differentiate these diseases not only forresearch purposes and therapeutic choices, but also forpatient diagnosis. Given the quick progression of the diseaseand how quickly patients lose their mobility and becomebedridden, they should be treated quickly by aninterdisciplinary team.

Despite greater awareness in recent years, many patientswith PSP remain undiagnosed or misdiagnosed for muchof their disease duration. As disease-modifying therapiesemerge it will be vital to intervene as early in the pathologicalprocess as possible. There is a therefore a need for a greaterawareness of PSP and the development of robust diagnosticclinical and investigational markers that predict whether anindividual with suspicious, but not “typical classical”features, will go on to develop PSP. Physicians shouldconsider PSP when rigidity and bradykinesia co-exist withearly falls. The patient should be examined carefully forslowing of downward saccadic eye movements and thepresence of square wave jerks. The presence of frankvertical ophthalmoparesis is of significant diagnostic helpbut it should also be borne in mind that this physical signmay take several years to develop in some patients.

References

1. Larner A.J. — Did Charles Dickens describeprogressive supranuclear palsy in 1857? Mov Disord2002.

2. Parkinsonian Syndromes By Guylaine Chiasson, MD,FRCPC; and Michel Dugas, MD, FRCPC TheCanadian Journal of CME / July 2002.

3. Dickson D.W., Hutton M.L. — Progressivesupranuclear palsy: pathology and genetics. BrainPathol. 17:74-82, 2007.

4. Williams D.R., Holton J.L., Strand C., et al. —Pathological tau burden and distribution distinguishesprogressive supranuclear palsy-parkinsonism fromRichardson’s syndrome. Brain. 130:1566-1576,2007.

5. Fabre N., Brefel-Courbon C., Rascol O. — ParkinsonPlus. La revue du praticien. 47:1077-1082, 1997.

6. Stacy M., Jankovic J. — Differential diagnosis ofParkinson’s disease and the parkinsonism-plussyndromes. Neurologic Clinics. 10(2):341-359.

7. Cardoso F., Jankovic J. — Progressive supranuclearpalsy. In: Donald B, Cabre DM (eds.):Neurodegenerative Diseases, W.B. Saunders,Philadelphia. pp. 769-783, 1994.

8. Litvan I., Agid Y., Calne D., et al. — Clinical researchcriteria for the diagnosis of progressive supranuclearpalsy (Steele-Richardson-Olszewski syndrome):report of the NINDS-SPSP international workshop.Neurology; 47:1-9, 1996.

9. Progressive Supranuclear Palsy Update Professor DBurn Professor of Movement Disorder Neurology andHonorary Consultant Neurologist, Institute for Ageingand Health, Newcastle University

10. Schrag A., Good C.D., Miszkiel K., et al. —Differentiation of atypical parkinsonian syndromeswith routine MRI. Neurology. 54:697-702, 2000.

11. Warmuth-Metz M., Naumann M., Csoti I., SolymosiL. — Measurement of the midbrain diameter onroutine magnetic resonance imaging: a simple andaccurate method of differentiating between Parkinsondisease and progressive supranuclear palsy. ArchNeurol. 58:1076-1079, 2001.

12. Burn D.J., Warren N.M. — Toward future therapiesin progressive supranuclear palsy. Mov Disord.20:S92-S98, 2005.

13. Kompoliti K., Goetz C.G., Litvan I., Jellinger K., VernyM. — Pharmacological therapy in progressivesupranuclear palsy. Arch Neurol. 55:1099-1102, 1998.

14. Stamelou M., Reuss A., Pilatus U., et al. — Short-term effects of coenzyme Q10 in progressivesupranuclear palsy: a randomized, placebo-controlledtrial. Mov Disord. 23:942-949, 2008.

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Progressive Supranuclear Palsy (PSP)