*Post Graduate Student , Dept of Medicine,
**Professor and Head, Dept of Neurology
Calicut Medical College


Abstract
Multiple system atrophy is a rare disorder involving pyramidal, extrapyramidal, cerebellar and autonomic nervous systems. Here we report a case which presented with sexual dysfunction to start with, followed by other system involvements.

Key words
striatonigral degeneration, sporadic olivopontocerebellar atrophy , Shy-Drager syndrome

Introduction
Multiple system atrophy (MSA) is a term introduced by Graham and Oppenheimer in1969 to describe a group of patients with a disorder of unknown cause affecting extrapyramidal, pyramidal, cerebellar and autonomic pathways. MSA included the disorders previously called Striato Nigral Degeneration (SND), sporadic
Olivo Ponto Cerebellar atrophy (OPCA), and the Shy-Drager syndrome (SDS) 1. The clinical syndrome can include various combinations of symptoms of autonomic dysfunction [ orthostatic hypotension, impotence, bladder and bowel dysfunction and defective sweating] as well as additional symptoms of nervous system such as rigidity tremor and loss of associated movements. Symptoms usually develop over a period of five years. Here we report a case having features of degeneration of cerebellar, extrapyramidal, pyramidal, and autonomic nervous systems which initially presented as sexual dysfunction.

Case report
45 year old goldsmith had been a heavy drinker of alcohol for 25 years with occasional consumption of cannabis , who noticed decreased sexual performance 3 years ago. He was advised to stop drinking which he complied. His performance gradually deteriorated to ejaculatory failure and to decreased sexual desire.
During the past 3years he also developed tremor of both hands which worsened on doing work, affecting his professional life. He has also developed a tendency to fall backwards and hence he started stooping forward with instability on standing. He has noticed difficulty in carrying food to mouth with precision. He had half a dozen falls with transient loss of consciousness and spontaneous recovery in a few seconds during washing face after meals. He also had a couple of falls during brushing teeth in the morning. He did not have any weakness or sensory symptoms. He had episodes of laughter and crying without provocation. He never had dyspnea, cough or stridor. He was not a diabetic or hypertensive . He was never treated for tuberculosis . His symptoms had progressively increased or developed over past three years despite treatment with modern medicine and alternative medicine.
On examination there was infrequent blinking and he had a mask like face. He was cooperative and his memory and intelligence were good. He cared of himself and there was no history of any delusion or hallucination. Cranial nerve examinations showed slow saccades, broken pursuit movements of eyeball, reduced upgaze and a brisk jaw jerk. There was cogwheel rigidity in the limbs with full power. Plantar reflex was extensor bilaterally. There were bilateral cerebellar signs as evidenced by positive finger nose test, knee heel test and dysdiadokokinesia and cerebellar type of speech.
Autonomic nervous system showed dysfunction [see table].
Urodynamic studies showed bladder with marked compliance and hypotonic detrussor.

Bedside tests for assessment of autonomic nervous system:
1. Heart rate response to deep breathing
Normally there is variability in heart rate during respiration, which is known as sinus arrhythmia. This is lost in autonomic dysfunction. Patient is asked to breathe deeply at a rate of six per minute. Continuous ECG is recorded for a minute, and the difference between the maximum and minimum heart rate in each respiratory cycle is calculated and the average is taken.

2. Immediate heart rate response to standing: [30:15 heart beat ratio]
On standing there is a decrease in venous return, cardiac output and the blood pressure which causes a reflex rise of heart rate. But the body will soon correct it to normal level so that it falls immediately. This adjustment is lost in autonomic dysfunction. ECG is recorded continuously in supine position and then with the patient standing for a minimum of 30 beats. Take the ratio of 30th RR interval to 15th RR interval. Take the average of three values.

3. Valsalva ratio:
The patient is asked to blow into a sphygmomanometer tube and maintain the pressure at 40mmof Hg for 15 seconds with continuous ECG recording during and 30 seconds into recovery. The valsalva ratio is calculated as the ratio of the longest RR interval during recovery divided by shortest RR interval during the blowing phase. Repeat thrice and take the average.

4. Postural fall in blood pressure:
On standing from supine position there is fall in blood pressure which is corrected immediately by the body. A fall of more than 30 mm of Hg in systolic pressure after 20 minutes of supine rest indicates autonomic failure. This fall persists for 5 minutes.

5. Increase in diastolic pressure on isometric exercise;
This is done using two sphygmomanometers. Maximum voluntary contraction is the maximum pressure exerted on hand grip. The patient is asked to maintain handgrip of about a third of maximum voluntary contraction for 5 minutes. Blood pressure is measured in each minute and the rise in diastolic pressure is assessed.

6. Cold pressor test:
Patient's hand is immersed in cold water (1-40 C) for 5 minutes and blood pressure is measured every minute. Assess the rise in diastolic pressure.

Bedside tests for ANS function

 

Though , a number of invasive and expensive tests like plasma noradrenaline on vertical lift ,vasopressin level in induced hypotension and baroreceptor sensitivity test are available, the above bedside tests are quite adequate for clinical testing of autonomic nervous system function.

This gentleman has been put on low dose of L-dopa and fludrocortisone. He has considerable symptomatic improvement. His postural syncope tremor and dysarthria improved but there was little improvement of sexual function at 2 weeks of therapy. He is on follow up.

Discussion
Diagnosis of multiple system atrophy is extremely difficult in early stages. Wenning et al analyzed the clinical features of 203 published cases of pathologically proven MSA. Most patients showed symptoms in their early fifties, with men more commonly affected than women (ratio of 1.3:1). Seventy four percent of patients suffered some degree of autonomic failure. Parkinsonism was the most common motor disorder (87%), followed by cerebellar ataxia (54%) and pyramidal signs (49%).Severe dementia s was most unusual. Incidence is about 4 per 100,000. Life expectancy has been 5years in early 20th century. Now it is about 7.5 years.

Diagnostic testing:
The diagnosis of Multi System atrophy during life is based on clinical features and thus it is only made with possible or probable certainty .Definite diagnosis requires pathologic confirmation by demonstration of glial cytoplasmic inclusions and absence of Lewy bodies. Glial cytoplasmic inclusions represent a cytoskeletal alteration in glial cells that results in neurononal degeneration. MRI of the brain and sphincter EMG, can be used as
confirmatory tests to aid clinical diagnosis. A characteristic of MSA is that afferent and central autonomic and neuroendocrine reflex pathways are selectively affected while postganglionic autonomic fibers are spared. This principle is made use of in using clonidine, a central alpha2 adrenoceptor agonist that stimulates growth hormone (GH) secretion, to test the function
of hypothalamic-pituitary pathways. Clonidine raised serum growth hormone in
patients with Parkinsonism and patients with pure autonomic failure but did not in those with
MSA. This finding suggests that the growth hormone responses to i.v. clonidine can
differentiate MSA from Parkinsonism and pure autonomic failure and suggest a specific alpha
2 adrenoceptor-hypothalamic deficit in MSA.
Brain Imaging : In patients with MSA, Magnetic Resonance Imaging (MRI) of the brain can detect abnormalities of striatum, cerebellum and brainstem .In up to 20% of MSA patients, however, MRI of the brain is normal. PET scanning may also be helpful.
Urodynamic Studies : Studies have reported that patients with MSA had early dysuria with or without chronic retention, frequently associated with a hypoactive detrusor and low urethral pressure.
Treatment:

Treatment for motor abnormalities in multiple system atrophy remains dismal[3,4].Following measures have been suggested for orthostatic hypotension.
Withdraw drugs that may precipitate postural hypotension
Sleep in as nearly vertical position as possible to minimize supine hypertension.
Volume repletion
High salt intake
Desmopressin to minimize fluid loss
Drugs such as
Fludrocortisone 0.1-0.5 mg
Indomethacin 50 mg thrice daily
Midodrin-alpha agonist
Dihydroxyphenyl serine- precursor of epinephrine
CPAP may be useful in cases of stridor.3


References:
1. Horacio Kaufmann: multiple system atrophy: current opinion in neurology, 11;351-355
2. A Schrag, Y Ben-Shlomo, N P Quinn Prevalence of progressive supranuclear palsy and multiple system atrophy: a cross-sectional study : Lancet 1999;354
: 1771-75
3. Alex Iranzo, Joan Santamaria, Eduard Tolosa, on behalf of the Barcelona Multiple System Atrophy Study Group: Continuous positive air pressure eliminates nocturnal stridor in multiple system atrophy; Lancet 356:329-30
4. Irwin J Schatz; Treatment of severe autonomic orthostatic hypotension :
Lancet:357 1060-61


 

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