-PROGRESSIVE SUPRANUCLEAR PALSY –

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A RARE CASE REPORT

ABSTRACT

A rare case of Progressive Supranuclear Palsy (PSP) is reported in an elderly male patient.  The pathophysiology, clinical features, diagnosis, differential diagnosis and management are reviewed in this article.

KEY WORDS

            Progressive Supranuclear Palsy

            Supranuclear Ophthalmoplegia

INTRODUCTION

Progressive Supranuclear Palsy (PSP) or Steele- Richardson – Olszewski Syndrome is a neurodegenerative condition affecting brainstem and basal ganglia.  Often misdiagnosed as Parkinson’s Disease.  It is characterized by supranuclear ophthalmoplegia, pseudobulbar palsy, axial rigidity and mild dementia.  Diagnosis is usually clinical and treatment is usually supportive.

CASE REPORT

A 80 year old patient presented with complaints of difficulty in speech for 6 months, history of unsteadiness of gait, frequent falls, loss of voluntary movement of eyeball and neck stiffness since 3 months.

The patient gave a classical history of inability to take food from the plate initially and gradual loss of movement of eyeball in the downward direction followed by gaze palsy in all directions.  He was not a known case of hypertension, diabetes mellitus, PTB.   There was no suggestive family history. 

On examination he was of average body built with mild pallor, no icterus .  PR-80 / min regular, BP – 140 / 80 mmHg.  Chest – Normal,                CVS – Normal P/A – No hepatosplenomegaly.  No engorged abdominal veins.

CNS examination

On examination of higher function he had emotional lability with outbursts of depression and euphoria.  Pseudo bulbar type of spastic dysarthria and   masked faces with decreased blinking of eyes, frontalis overactivity. (Photograph 1).  Normal recent, immediate and remote memory.

Eye movement was fixed and looking straight and fixed gaze.  Voluntary eye movements were restricted in all directions.   Doll’s eye movement was present in all directions.  Bell’s phenomenon was absent  (Photograph – 2,3,4).  Other cranial nerves were intact.  There was hypertonia in all limbs with power grade 5 in all limbs. DTR were brisk and   superficial reflex were intact, Plantar B/L Flexor, Gait was stiff.  Sensory system and autonomic functions were normal.  Neck Stiffness and truncal rigidity were present with peripheral nerves intact.  

INVESTIGATION

Routine investigations were normal. They were Hb – 10.2 gm%, DC – N50 L32 E15 M3, TLC-7800/mm³, FBS – 89mg/dL, ESR -  10mm in 1^st hr., S. urea – 18 mg/dL, S. creatinine – 0.6mg/dL, FBS – 89 mg/dL. S. Cholesterol – 112 mg/dL, HDL – 35 mg/dL, VLDL – 20mg/dL, S. Triglyceride – 100 mg/dL, LDL – 57mg/dL.

CT Scan – Brain – Normal.

The patient was clinically diagnosed as a case of Progressive Supranuclear Palsy (PSP).  He was started on Tab. Cereloid, Tb. Ramloz, Cap. Trivastal LA and discharged with advise to follow up.

DISCUSSION

Definition : Progressive supranuclear palsy is a progressive late onset neurodegenerative disorder characterised by supranuclear.  ophthalmoplegia, pseudobulbar palsy, axial rigidity, mild dementia, dysarthria, dystonic rigidity of neck and trunk, and postural instability. ¹ 

Epidemiology : PSP occurs all throughout the world.  Male to female ratio 3:2.  Mastaglia et al (1973) estimated the incidence to be 4 per million in Western Australia.  Globe et al (1988) estimated the incidence to be 1.39 per 100,000.¹

Pathophysiology : Key feature of PSP is formation of Neurofibrillary Tangles (NFT).  There is also presence of gliosis and neuronal loss in Globus.Pallidus, Subthalamic nuclei, substantia nigra, pretectal nucleus, superior colliculi, pontine nuclei, pedunculopontine nucleus (PPN) and interstitial nuclei of Cajal. ^2,3

Gait instability is linked to involvement of PPN while the involvement of interstitial nucleus of Cajal.  may cause axial and neck rigidity.  Disordered eye movement is due to involvement of tectal and pretectal nuclei. ⁴

NFT contain abnormally phosphorylated “tau protein” so this disease is included in the entity tauopathy.   Majority of cases are sporadic although few familial cases have been reported.

In PSP unlike Parkinson’s Disease striatal neurons, including cholinergic interneurons are affected as well as negrostrial dopaminergic neurons.  Levels of dopamine and homovanillic acid are decreased in  Caudate and Putamen.

Clinical Features : Usually the disease strikes at the age of 40 years.  Early falls and characteristic eye movement disorder are the initial feature.  Other features include frontal lobe impairment, pseudobulbar palsy, bradykinesia, rigidity and pyramidal signs.  Patient usually falls backwards while walking. ^5,6,7

Neurological Features : Neurologically there may be low volume spastic dysarthria.  On examination a clinical picture of an akinetic rigid Parkinsonian syndrome is seen.  But in contrast PSP patients have a flexed posture of limbs, neck, trunk and hold neck stiffly in extension.  Tremor is not a feature of this condition.   Pseudobulbar palsy develops usually at a certain stage.  Difficulty in swallowing, both liquids and solids may require nasogastric tube.  Neurobehavioral disturbance occur in 50% patients. They consist of depression, irritability and emotional liability. ^6,7

The patient has a frozen appearance with decreased blinking,frontalis over activity and fixed gaze.

Neuroophthalmological Features : There is development of supranuclear downgaze palsy due to damage to substantia nigra pars reticulata.  Optokinetic response to downward moving stimulus are impaired.   Patient may find difficulty in looking downwards.  Ultimately severe ophthalmoplegia develops in all directions.  Other features like Bell’s phenomenon may occur.  In early states of PSP gaze palsy is truly supranuclear i.e. full excursions of eye movement in all directions can be obtained with the oculocephalic(doll’s head) maneuver.  (Ref. Photograph 2,3,4)  With time however there is loss of oculocephalic, reflex and  Bell’s Phenomenon.⁵

Eyelid Features : Some patients may have difficulty in voluntarily opening their eyes in absence of any visible activity in orbicularis oculi.  This is called apraxia of eyelid opening and is caused by sustained inhibition of levator palpebrae.  Brow may be sharply raised (COLLIER’s SIGN) due to active contraction of frontalis muscle.  Some patient may have apraxia of eyelid closure with complete inability to close eye to command but closure can occur during sleep.⁵

Diagnosis : Diagnostic evaluation are carried out to exclude other conditions that may mimic similar symptoms like hydrocephalus, multiple infarction.  MRI may show brainstem atrophy.  Loss of strial dopamine receptors can be detected by SPECT/PET.  Specialized neurophysiological studies have shown lose of normal auditory startle response.  However the diagnosis of PSP remains clinical. ^8,9

Differential Diagnosis : Clinically PSP has to be differentiated from Parkinson’s Disease, Multiple System Atrophy (MSA), Cortical Lewy Body Disease (CLBD), Corticobasal Degeneration (CBD)

1. Parkinson’s Disease is differentiated by presence of generalized rigidity, tremor and good response to levodopa.

2. MSA presents with an early age of onset, ophthalmoplegia is not marked and there is presence of progressive ataxia and autonomic impairment.

3. CLBD  present with hallucinations & mental fluctuation, dementia and sleep disturbances.

4. CBD  present with apraxia, ophthalmoplegia is not marked, there is cortical sensory loss, myoclonus and alein limb sign.

Treatment and Prognosis : The disease is usually progressive and median survival is usually less than 6 years.  Death is usually due to aspiration pneumonia and as a consequence of injury sustained during fall.  Response to Levodopa occurs in few case only.  Levadopa can help the slowness, stiffness and balance problems in PSP to a degree but usually not the mental, speech, visual or swallowing difficulties and usually loses its benefit after 2- 3 years.

Some patients may require a dosage of 1500 mg of Levodopa to show an improvement but side effects such as confusion, hallucination and dizziness can occur at those level.  Usually patient should receive standard (Levodopa/Carbidopa) preparation rather than CR controlled release forms.¹⁰

Bromocriptine, pergolide, pramipexole, ropinirole have rarely provided benefit in PSP.  Side effects include hallucination and confusion.

Antidepressants have shown modest benefit.  Amitryptiline has shown some benefit in movement disorder in PSP.  Should be started at a dose of 10 mg OD at bedtime.  Increased slowly and taken in divided doses twice in a day.  After 80 mg/day the S/E increases to unacceptable levels.  Also provides good sleep benefit. Important side effects are constipation, dry mouth, confusion, micturation difficulties.

Amantadine can be effective in PSP.  Helps gait disorder more but it lasts only for few months.  S/E Dry mouth, constipation, confusion, swelling of ankles.  Zolpidem was found in one double trial to help some aspects of PSP at a dose of 5 mg. Newer drugs like Efaroxan have proven ineffective. Botox - A very dilute solution can be used by neurologist to be injected into eyelid muscles as a temporary remedy for abnormal involuntary eyelid closure.  Also can be used for involuntary bending of head but this can cause weakness of swallowing muscle, which is already impaired in PSP

CONCLUSION

Patients of progressive supranucelar palsy are often misdiagnosed as cases of Parkinson’s Disease and it is only after the use of levodopa which proves disappointing in PSP that a diagnosis of progressive supranucelar palsy is made.  Treatment for progressive supranuclear palsy is disappointing.  The prognosis is bad but future research can bring some hope for this rare but progressive disease.
 

REFERENCE

1.                  Leenders KL, Frackowiak SJ, Lee AJ – Steele Richardson Olszewski Syndrome – Brain III; 615; 1988.

2.                  Gearing M, Oslon DA, Wattis RL.  Progressive supranuclear Palsy : neuropathologic and clinical heterogeneity: Neurology : 44 : 1015; 1994.

3.                  Collins SJ, Ahlskog JE, Parisi JE et al PSP : Neuropathologically based diagnostic criteria : J. Neurol : Neurosurg. Psych 58; 167-163; 1995.

4.                  Daniel SE, Debreum VMS, Lee AJ : The clinical and pathological spectrum of SRO :  A reappraisal : brain 118 : 759-770; 1995.

5.                  Troost BT, Daroff RB.  The ocular motor defects in PSP : Ann. Neurology : 397 – 1977.

6.                  Richardson JC, Steele J, Olszewski J.  Supranucelar ophthalmoplegia, pseudobulbar palsy, nuchal dystonia and dementia Trans Am. Neurol Assc. 88; 25; 1963.

7.                  Steele JC : Progressive Supranuclear Palsy : Brain 95 : 693; 1972.

8.                  Blin J. Baron JC, Dubuis B et al.  PET study in Progressive Supranucelar Palsy : Brain hypometabolic pattern and clinico metabolic correlation.  Arch neurol : 47 : 747 – 752; 1990.

9.                  Ferederio F., Slimmer IL, Luasiero V et al : Proton Magnetic Resonance Spectroscopy in Parkinson’s Disease and Progressive Supranuclear Palsy : J. Neurol Neurosurg Psych : 62; 239-49; 1997.