What is multiple system atrophy?

Multiple system atrophy (MSA) is a rare neuro-degenerative disease marked by a combination of symptoms affecting movement, blood pressure, and other body functions; hence the label "multiple system" atrophy. The cause of MSA is unknown.

According to the American Autonomic Society, Multiple System Atrophy (MSA) is a sporadic, progressive, adult-onset disorder characterized by autonomic dysfunction, parkinsonism and ataxia (a failure of muscular coordination) in any combination.

The features of the disorder include:

* Parkinsonism
* Cerebellar or corticospinal signs
* Orthostatic hypotension
* Impotence
* Urinary incontinence or retention, usually preceding or within two years after the onset of the motor symptoms
* Parkinsonian and cerebellar features commonly occur in combination. However, certain features may predominate. 
 

How common is multiple system atrophy?

Between 25,000 and 100,000 American have multiple system atrophy.

The incidence (new case per 100,000 person years) for ages 50 to 99 years is 3.0 (Bower et al, 1997), or about half as frequent as progressive supranuclear palsy (PSP). 
 

What are the various forms of MSA?

The term "Multiple System Atrophy" is synonymous with striatonigral degeneration (SND) when Parkinsonism predominates, olivopontocerebellar atrophy (OPCA) when cerebellar signs predominate, and Shy-Drager syndrome when autonomic failure is dominant.

Symptoms of multiple system atrophy vary in distribution, onset and severity from person to person. Because of this, three different diseases were initially described to encompass this range of symptoms:
 

• Shy-Drager syndrome
• Striatonigral degeneration
• Olivopontocerebellar atrophy.

In Shy-Drager syndrome, the most prominent symptoms are those involving the autonomic system, the body system that regulates blood pressure, urinary function, and other functions not involving conscious control. Striatonigral degeneration causes parkinsonian symptoms such as slowed movements and rigidity, while olivopontocerebellar atrophy principally affects balance, coordination, and speech.

These diseases are now considered forms of multiple system atrophy. 
 

What is Shy-Drager syndrome?

The term Shy-Drager syndrome, named after the two physicians who first described the neurologic symptoms, is still used to refer to Multiple System Atrophy. However, Shy-Drager more specifically describes an MSA whose symptoms involve a failure of the autonomic nervous system. Those symptoms include orthostatic hypotension, an abnormal drop in blood pressure when a person sits or stands that causes lightheadedness and blackouts, as well as tiredness, blurred vision, lack of muscle coordination and pain in the back of the neck. 

How can I tell if I have multiple system atrophy?

Many patients with multiple system atrophy will not receive the correct diagnosis during their lifetime. This is due to the difficulty in differentiating multiple system atrophy from other disorders (including relatively common degenerative disorders such as Parkinson’s disease and more rare ones such as pure autonomic failure).

Shy-Drager may be difficult to diagnose in the early stages because it can take years for key symptoms to develop. For most patients, the unstable, fluctuating blood pressure causes severe headaches.

The mean age of onset is 54. Multiple system atrophy usually occurs after age 50, with a slightly higher incidence in males. Patients usually have autonomic nervous system dysfunction first. Genitourinary dysfunction (difficulty with urination) is the most frequent initial complain in women, while impotence is the most frequent initial complaint in men.

Orthostatic hypotension (a large drop in blood pressure upon standing) is common and may cause dizziness, dimming of vision, head or neck pain, yawning, temporary confusion, slurred speech, and if the hypotension is severe, the patient may "faint" upon arising from a recumbent position.

In spite of low blood pressure while standing, it is common for multiple system atrophy patients to have high blood pressure when lying down.

A fall in blood pressure following meals or in hot weather or following infection is quite common.

When MSA begins with non-autonomic features, imbalance is the most common feature. This difficulty in maintaining balance may be due to either cerebellar or Parkinsonian abnormalities. Some patients complain of stiffness, clumsiness, or a change in handwriting at the onset of MSA.

The concurrent involvement in MSA of multiple brain systems subserving movement, including the striatum, cerebellum, and cortex, leads to the movement disorder as often being the most profound disability. Hoarseness or even vocal paralysis are relatively common, as are sleep disturbances, including snoring and sleep apnea. The ability to swallow foods and liquids may be impaired. 
 

What are the symptoms of MSA?

Multiple system atrophy can manifest in a variety of different ways and progresses in an unpredictable sequence and time scale for each patient. It is important to understand that having a diagnosis of MSA does not mean that you will experience all the symptoms from the range below.

MSA can cause a wide range of symptoms, including:

• stiffness or rigidity
• freezing or slowed movements
• postural instability; loss of balance; incoordination
• Orthostatic hypotension, or a significant fall in blood pressure when standing, causing dizziness, lightheadedness, fainting, or blurred vision 
• male impotence
• urinary difficulties
• constipation
• speech and swallowing difficulties
• blurred vision

The Parkinsonism of MSA is generally an akinetic rigid syndrome, similar to that of PSP. Rest tremor may occur but is not a predominant feature. Postural instability is common. Parkinsonism is generally the most common initial sign and eventually develops in about 90% of all patients.

The cerebellar signs include finger-to-nose or heel-shin dysmetria, gait ataxia, intention tremor and nystagmus. Cerebellar signs are the first feature on only about 5% of patients. Cerebellar signs are observed in 50% of cases. Sporadic OPCA evolves into MSA in roughly 25% of cases within 5 years.

Autonomic dysfunction includes impotence (the most common male sign), postural hypotension with syncope, urinary incontinence and retention, and fecal incontinence.

Signs and tests

There are many disorders with symptoms which overlap with those of MSA, therefore diagnosis is usually carried out by a Neurologist at the request of a GP. Information about the history of an individual's symptoms and an examination will be performed. There are also hospital tests that help in the diagnosis.

The initial diagnosis of MSA is usually made by carefully interviewing the patient and performing a physical examination. However, more testing is often needed to confirm the diagnosis.

Among the tests that are helpful in determining the presence of MSA are several types of brain imaging including computerized tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET).

Pharmacological challenge tests (administering certain drugs in the presence of various types of movements of the patient) may also be of help. In those patients with typical parkinsonian signs, an incomplete and relatively poor response to dopamine replacement therapy (such as l-dopa [Sinemet]) may be a clue that MSA is present.

An eye examination may reveal atrophy of the iris and paralysis of eye muscles. Postural hypotension (drop in blood pressure associated with change in position) is evident. A neuromuscular examination shows abnormal reflexes and may show severe muscle wasting (atrophy). Parkinsonian movements (tremor, rigidity, and slow movements similar to Parkinson's disease) are common.

Diagnosis is largely clinical as there are no specific tests during life to confirm the disease. A neurologist makes the diagnosis based on the history of symptoms and the findings on physical examination as well as ruling out other causes.

Testing may include:
 

• Plasma norepinephrine levels
• Urine examination for norepinephrine breakdown products (urine catecholamines)
• MRI of head to rule out other pathology. There are no specific abnormalities on imaging associated with MSA

 

What are the complications of MSA?

Multiple system atrophy progresses over the course of several years to cause more widespread and severe symptoms. Orthostatic hypotension can cause fainting and falls. Loss of coordination, slowed movements, and rigidity can interfere with activities of daily living. Some patients with MSA have mild loss of cognitive abilities, with impairments in attention and speed of thinking.

Complications include:
 

• Progressive loss of ability to walk or care for self 
• Difficulty performing daily activities
• Injuries from falls/fainting
• Side effects of medications

 

Are there any treatments for MSA?

Currently there is no cure for MSA and no known means to slow progression. Treatment aims to reduce the disabling effect of the symptoms so that as full a life as possible can be led. The treatment is aimed at controlling symptoms such as postural hypotension and parkinsonian movements.

The fluctuating blood pressure makes the condition difficult to treat. Dietary changes, such as increasing salt and fluid intake, may help elevate blood pressure fluctuations.

A number of drugs can be used to treat the various symptoms of MSA, although they become less effective as the disease progresses.
 

• Levodopa and dopamine agonists used to treat Parkinson's disease are sometimes effective for the slowness and rigidity of multiple system atrophy.
• Orthostatic hypotension can be improved with fludrocortisone, midodrine, or other drugs that raise blood pressure.
• Male impotence may be treated with penile implants or drugs.
• Incontinence may be treated with medications or catheterization.
• Constipation may improve with increased dietary fiber or laxatives.
•  A speech-language pathologist may be able to offer strategies for improving swallowing and speaking. Use of softer foods may improve the ability to swallow. A breathing or feeding tube may have to be surgically inserted to manage swallowing and breathing difficulties.
• A gastrostomy tube, which delivers foods directly to the stomach, is occasionally needed later in the disease course.

Levodopa may improve movement and balance. Multiple system atrophy patients either do not respond or respond poorly to levodopa. Doses of 1 to 1.5 gram per day must be used before unresponsiveness is declared, but generally only about 1/3 of patients respond.

Carbidopa may reduce the side effects of Levodopa and make the Levodopa work better. The response to medications may be disappointing. Many affected individuals respond poorly to treatment with anticholinergics or Levodopa.

Autonomic failure can be treated with salt supplements, florinef, and midodrine. It has been suggested that MSA patients may benefit from replacement of central norepinephrine or epinephrine with precursors such as dihidroxyphenylserine. There is no effective treatment for the cerebellar disturbance.

Anticholinergic medications may be used to reduce early or mild tremors.

Sympathomimetics, vasoconstrictors like midodrine, beta-blockers, MAO inhibitors, vasopressin, 9-fluohydrocortisone, or other medications may be used to treat low blood pressure (postural hypotension).

A heart pacemaker programmed to stimulate the heart to beat at a rapid rate (faster than 100) may increase the blood pressure for some people.
 
 

Expectations (Prognosis)

The probable outcome is poor. There is a progressive loss of mental and physical functions until general debilitation develops. Early death is likely. Most people who are diagnosed with Shy-Drager syndrome die within seven to 10 years after symptoms begin. Pneumonia is the most common cause of death, although irregularities in heartbeat or choking may be responsible for death in some patients.

Breathing problems such as aspiration, stridor (high-pitched breathing sounds due to airway obstruction), or cardiopulmonary arrest are common causes of death. 
 

What is the progression of multiple system atrophy?

Disease progression in multiple system atrophy is quicker than in Parkinsonism but similar or slightly slower to that of PSP (Bower, 1997). Almost 80% of patients are disabled within 5 years of onset of the motor symptoms, and only 20% survive past 12 years. The mean survival is roughly 6 years.

Rate of progression differs in every case and speed of decline may vary widely in individual patients.
 
 
 

Quality of Life in MSA: A National Survey.
S. Dickinson, E. Garland, G. Farley and T. Davis, Vanderbilt University, Nashville, TN, USA
 

Diagnosis:Multi-System Atrophy

 
The most common cause of parkinsonism worldwide is idiopathic Parkinson's disease (IPD), a progressive neurodegenerative condition due to dopaminergic neuronal loss in the substantia nigra, pars compacta. Clinical features include a resting supination-pronation tremor, cogwheel rigidity, bradykinesia, loss of postural reflexes, the freezing phenomenon, and a good therapeutic response to levodopa therapy. Other features seen later in the course of the disease include hypophonia, autonomic dysfunction, and bradyphrenia. Diagnostic confusion arises,  when patients present with parkinsonism associated with atypical features, such as

• oculomotor abnormalities, 
• marked autonomic dysfunction, 
• cerebellar involvement, 
• apraxias, and/or pyramidal tract involvement. 

The coexistence of these features with parkinsonism implies involvement of multiple neurological systems. Parkinsonism accompanied features of pyramidal, autonomic, intellectual (mild subcortical dementia), and cerebellar dysfunction. Several distinct clinical entities with mixtures of parkinsonism and degeneration of other neurological systems are now recognized. Distinguishing among these processes is more than an academic exercise, since accurate diagnosis carries therapeutic and prognostic significance. In part, this is due to differences in the pathophysiology and anatomy of the different diseases. The prognosis for successful treatment of Parkinson's disease is quite good, since the primary defect lies in loss of the dopaminergic cells of the substantia nigra. Replacement of dopamine effectively treats the underlying physiologic abnormality, though it does not address the pathophysiology of disease progression.

Prognosis in conditions resulting from degeneration of the striatum or other basal ganglionic structures is much worse, since the primary defect lies in loss of cells carrying dopaminergic receptors. Dopamine replacement is not as effective in helping these patients. 

The differential diagnosis of parkinsonism accompanied by atypical features is broad and includes the 
Parkinsonism Plus syndromes 

multisystem atrophies, 

progressive supranuclear palsy, 

cortical-basal ganglionic degeneration, 

progressive pallidal atrophy, 

diffuse Lewy body disease 

Alzheimer's disease with parkinsonian features, 

Pick's disease, 

hederodegenerative diseases (Wilson's, Hallervorden-Spatz, Huntington's disease, etc.) 

and secondary parkinsonism (vascular, drug induced, infection, prion disease, toxins, trauma, mass lesions, hydrocephalus, hypothyroidism, paraneoplastic, hepatocerebral degeneration, and syringomesencephalia). 

Of the various causes, the Parkinsonism Plus syndromes and secondary parkinsonism are the most common. Infectious possibilities include encephalitis lethargica, HIV, syphilis, and SSPE. Serologic tests can exclude syphilis and HIV infection, and the clinical course of encephalitis lethargica or SSPE are rapidly progressive conditions. 

History and tests should first exclude anti-psychotic or anti-emetic drug exposure, toxin (CO, Mn, Hg, MPTP, CS2, methanol, cyanide) exposure, multiple head traumas, multiple strokes, or metabolic abnormalities. Prion diseases, especially Creutzfeldt-Jakob and Gerstmann-Straussler-Scheinker (Mad Cow, Familial Fatal Insomnia) disease, present with a more rapid, aggressive course and more profound dementia. 

Neuroimaging can exclude the possibility of hydrocephalus and mass lesions. The possibility of normal pressure hydrocephalus, consisting of the triad of dementia, gait disturbance, and urinary incontinence might be considered. 

• The Parkinsonism Plus syndromes include an array of neurodegenerative conditions characterized by parkinsonism plus other evidence of neurological dysfunction. 
• In Diffuse Lewy Body disease, parkinsonism is accompanied by cortical dementia with varying levels of attention, early hallucinations, and psychosis. Autonomic dysfunction is common, and pyramidal signs may be seen, but cerebellar dysfunction is not found. Mild subcortical dementia is not consistent with this diagnosis. 
• In cortical-basal ganglionic degeneration (CBGD), parkinsonism is accompanied by ideomotor apraxias, the alien limb phenomenon, cortical reflex myoclonus, cortical sensory loss, marked asymmetry of involvement, and focal rigidity and dystonia with contractures. 
• In progressive supranuclear palsy (PSP), parkinsonism is accompanied by a prominent supranuclear gaze disturbance. 
• Multisystem atrophy (MSA) is a progressive, sporadic disorder characterized by parkinsonism in association with varying degrees of cerebellar, pyramidal, intellectual, and autonomic dysfunction. Classically, this includes three separate entities - 
• Striatonigral degeneration (SND) (parkinsonism poorly responsive to levodopa and frequently associated with cervical dystonia), 
• Olivopontocerebellar atrophy (OPCA) (parkinsonism with cerebellar dysfunction), 
• Shy-Drager syndrome (SDS) (parkinsonism with autonomic dysfunction). 
• Because of the clinical overlap and common pathologic finding of an intracytoplasmic oligodendroglial inclusion body, these entities are now lumped together. 

Usual treatment: 

• low dose levodopa 
• physical therapy. 
• orthostasis was treated with increased fluid intake, 
• further symptomatic treatment regarding urinary incontinence/erectile dysfunction, sleep disturbance 

Introduction
 

Graham and Oppenheimer coined the term multisystem atrophy (MSA) in 1969 to reflect the clinical relationships among three previously described parkinsonian syndromes: Shy-Drager syndrome (SDS), olivopontocerebellar atrophy (OPCA), and striatonigral degeneration (SND). Each shares features of parkinsonism along with variable degrees of pyramidal, cerebellar, and autonomic dysfunction. Subsequent pathological studies demonstrated a shared intracytoplasmic, eosinophilic oligodendroglial inclusion in each of these conditions, further supporting their clinical relationship. Though many neurologists still diagnose the individual syndromes, the generic term, multisystem atrophy, is now considered the preferred designation by most movement disorder specialists. However, the oligodendroglial cystoplasmic inclusions and intraneuronal cytoplasmic inclusions that are characteristic of the condition may be found in some patients with cortical basal-ganglionic degeneration (CBGD) and progressive supranuclear palsy (PSP). It is unclear if these "markers" simply represents non-specific "tombstones" without any clear pathophysiologic significance.

Epidemiology
 

The true prevalence of this condition is not known. Various studies have suggested an incidence of 3.6% to 22% among patients diagnosed with parkinsonism. The mean age of disease onset is 52.5 years with a mean age of death ranging from 60-65 years. Fewer than 4% of cases begin between the ages of 30-39 years and 70-79 years respectively. The vast majority (92%) of cases begin between the ages of 40-69. Survival from the age of symptom onset to death ranges from 5.5-9.4 years. There is a slight male predominance with a gender ratio of 1.1:1 to 1.9:1.

Clinical Features
 

Patients with MSA may present with a variety of clinical manifestations, either fitting one of the distinct subtypes (SND, OPCA, SDS) or with a combination of signs reflecting involvement of pyramidal, basal ganglia, cerebellar, and autonomic systems. Traditionally, the designation striatonigral degenearation was given to patients with predominant parkinsonism and pathological demonstration of striatal degeneration at autopsy. There is no clinical feature that clearly distinguishes SND from idiopathic Parkinson's disease (IPD), but tremor is less prominent, response to levodopa therapy is poor, and cervical dystonia (usually presenting as anterocollis) is more prominent in the former. OPCA was diagnosed in patients with parkinsonism associated with ataxia and any number of added findings including dyskinesias, cranial nerve palsies, optic atrophy, retinal degeneration, amyotrophy, peripheral neuropathy, supranuclear ophthalmoplegia, and/or dementia. Shy-Drager syndrome was diagnosed in patients with parkinsonism and prominent autonomic failure. Currently, the designation of MSA with a particular subtype (SND, OPCA, SDS) is used. In some cases, the designation MSA alone is used, when the patient does not fit into a clear subtype.

• Autonomic symptoms are present in 74-97% of patients with MSA with 55% showing urinary incontinence, 18% with urinary retention, 80% with impotence, and 68% with postural hypotension (usually mild to moderate with rare syncope). Three-fourths of patients develop autonomic symptoms up to four years before the onset of other neurological compromise. 
• Parkinsonism is present in 90-100% of patients diagnosed with MSA, with bradykinesia and rigidity found in 74% and tremor in 66%. Tremor is more common in MSA of SND subtype, though the classic pill-rolling tremor at rest is uncommon. 
• Cerebellar ataxia is present in 49% of patients diagnosed with MSA, including 79% of those diagnosed with the OPCA subtype, 60% of those with the SDS subtype, and 20% with the SND subtype. 
• Dysmetria of the upper extremities is less common. 
• Nystagmus has been documented in 25% of patients. 
• Pyramidal signs occur in 61% of patient diagnosed with MSA, with extensor plantar responses and hyper-reflexia seen in 41% and 46% of patients, respectively. A smaller percentage (10%) of patients demonstrate spasticity, though spastic paraparesis does not appear to occur. 
• Intellectual impairment is usually mild, corresponding to a mild subcortical dementia. Severe intellectual impairment is rare, seen in approximately 2% of cases. 
• Emotional lability may be seen in advanced disease. 
• Other clinical features include dysarthria (present in virtually all patients), respiratory stridor (34% of patients), anisocoria (in 8% of patients and associated with a Horner's syndrome in 5%), excessive snoring and vocal cord abductor palsy, and dystonia (including anterocollis, torticollis, focal limb dystonia, axial dystonia, and orofacial dystonia in 12% of untreated cases). 
• Oculomotor dysfunction is common and includes saccadic pursuit in 68%, hypometric saccades in 65%, limitation of upgaze in 39%, limitation of downgaze in 7%, and limitation of horizontal gaze in 7% of cases. 

Diagnosis
 

In diagnosing parkinsonian syndromes, one must first attempt to distinguish IPD from other causes. At times, this is extremely difficult; but the exercise has prognostic and therapeutic implications. Factors that help make this distinction include symmetry of symptoms, absent or minimal tremor, early autonomic dysfunction, early falling, prominent postural instability, and a poor response to levodopa therapy, with each of these features seen more prominently in non-IPD parkinsonism. Definitive diagnosis of MSA requires autopsy, but clinical criteria for diagnosis of SND and OPCA subtypes have been developed. The diagnosis of possible MSA, SND subtype may be made in any patient with parkinsonism and a poor response to levodopa therapy. The diagnosis of probable MSA, SND subtype also includes evidence of autonomic dysfunction, cerebellar signs, pyramidal signs, dystonia, or abnormal responses to sphincter EMG. The diagnosis of possible MSA, OPCA subtype may be made in any patient with a sporadic, adult-onset cerebellar syndrome associated with parkinsonism. The diagnosis of probable MSA, OPCA subtype also includes evidence of pyramidal signs, autonomic failure, oculomotor disturbances and/or pathologic sphincter EMG.

Diagnostic testing is aimed at supporting the clinical diagnosis, by demonstrating evidence of autonomic dysfunction and/or radiological clues, and excluding other potential causes of parkinsonism, such as toxin exposure, hydrocephalus, cerebral infarction, brain tumors, and infections. Tests of autonomic function (tilt table, plasma catecholamine levels) help to confirm suspicions of autonomic failure, but do not reliably distinguish the autonomic failure seen in MSA from that seen in IPD. However, external urethral or rectal sphincter EMG appears to be a relatively specific test for MSA, in that 98.7% of patients with MSA show signs of denervation and reinnervation while other patients with parkinsonism show normal responses to sphincter EMG. Neuroimaging is generally unrevealing and used primarily to eliminate other causes for parkinsonism. In some cases, putaminal abnormalities are seen on T2-weighted images, but this finding is not specific for MSA. In rare cases of OPCA significant brainstem and cerebellar atrophy may be seen. 

Definitive evidence requires pathological confirmation at the time of autopsy. In MSA, SND subtype one sees atrophy and discoloration in the putamina and depigmentation of the substantia nigra. Microscopically, there is severe neuronal loss and gliosis in the putamina, substantia nigra, globus pallidus, caudate, and subthalamic nucleus. Lewy bodies may rarely be found. In MSA, OPCA subtype one sees degeneration of the inferior olives, ventral pontine nuclei, and cerebellar cortex. And in MSA, SDS subtype the major pathologic lesion is found in the thoracic and upper lumbar intermediolateral gray column of the spinal cord, where sympathetic preganglionic neurons lie.

Treatment

As in early cases of idiopathic Parkinson's disease, the mainstay of treatment in patients with MSA is physical and occupational therapy to maintain mobility. Because of prominent problems with dysarthria and dysphagia, speech therapy is an important addition to this regimen. Otherwise, there is no specific therapy for MSA. Medical treatment is aimed at alleviating the extrapyramidal and autonomic dysfunction, though success is generally limited. The majority of patients show no or modest improvement with levodopa therapy. Up to 1/3 of patients with MSA, however, will show a moderate to good response with levodopa therapy, but this response is generally short-lived (lasting only 1 to 2 years). Treatment with levodopa is recommended for all patients, because of the chance for some improvement. Interestingly, the commonly encountered levodopa-induced dyskinesias seen in patients with IPD do not commonly occur in patients with MSA. Anticholinergics and amantadine may provide some symptomatic relief, but their use is limited by the development of orthostatic hypotension in many patients. Symptomatic treatment of orthostasis includes elastic stockings, increased salt and water intake, and mineralocorticoids, but is generally not very effective. Impotence may be treated with various measures, including penile implants and intracavernosal papaverine injections. Urinary incontinence may be treated with peripherally acting anticholinergic drugs. Urinary retention may be treated with indwelling catheters or intermittent catheterization. Respiratory stridor may be treated with tracheostomy. Sleep apnea may be treated with CPAP or tracheostomy in severe cases. Severe dysphagia may be treated with enteral
feeding. Dystonias may be treated with botulinum toxin injections.

Prognosis

MSA is a progressive neurodegenerative disease that is uniformly fatal (ed. but then life is also uniformly fatal). Mean survival is 6 years with a considerable range (2-20 years, ed. we can put that up to 40 - Harriet in Hawaii). Factors portending a faster progression and shorter survival include older age of onset and the presence of more than one clinical feature. (ed. being active and creative can stretch it way beyond what you might think, as can tenacity and sheer will - id)
 

 Irwin J. Schatz, MD 
 

1 July 1996 | Volume 125 Issue 1 | Pages 74-75
 

A recent consensus statement generated by the American Autonomic Society and the American Academy of Neurology [1] defines the various primary neurogenic causes of autonomic dysfunction. Implicit in this document is the need to bid good-bye to the use of the term "Shy-Drager syndrome" to identify a condition that was first described in 1962 [2]. 

Milton Shy and Glen Drager detailed the clinical features of two patients who had both orthostatic hypotension and central nervous system signs, and they carefully studied the neuropathologic changes in one of these patients [2]. Their conclusion that orthostatic hypotension and central nervous system dysfunction were probably related is obvious today but at the time seemed prescient. Although some previous reports had described these disparate phenomena in the same patients [3,4], no one had claimed that the two were related. Shy and Drager described several aspects of autonomic dysfunction--in addition to orthostatic hypotension--and meticulously delineated various signs of degeneration of the cerebellar, extrapyramidal, and pyramidal systems. Since their seminal report, burgeoning interest in autonomic disorders has spawned studies outlining the clinical and neuropathologic findings in such patients [5,6]. This research resulted in a far greater understanding of the interplay between structural defects and functional outcomes but inevitably added to a confusing array of terms. 

"Multiple system atrophy" is now the favored term; the condition is defined as a sporadic, progressive, adult-onset disorder characterized by autonomic dysfunction, parkinsonism, and ataxia in any combination. Its features include "parkinsonism (usually with a poor response to Levo-dopa), cerebellar or corticospinal signs, and orthostatic hypotension, impotence, and urinary incontinence, or retention ... when autonomic failure predominates, the term Shy Drager syndrome is often used" [1]. 

The current nosology for autonomic disorders is best summarized as follows: 1) primary (cause unknown), which includes pure autonomic failure (previously called idiopathic orthostatic hypotension or the Bradbury-Eggleston syndrome) and in which no neurologic defects other than autonomic dysfunction are present; and 2) multiple system atrophy, as described above [1]. Secondary autonomic failure encompasses diseases in which the lesion (broadly defined) is known (for example, diabetes mellitus, amyloidosis, dopamine beta-hydroxylase deficiency, and drug toxicity). 

Complicating this construct is the fact that some patients with pure autonomic failure may progress after a period of stability into multiple system atrophy, which affects some but not all areas of the central nervous system in various ways. Graham and Oppenheimer [7] accordingly wondered if there were more than one disease process. A key feature, autonomic dysfunction (with its resultant orthostatic hypotension), may or may not be associated with cerebellar or parkinsonian features, attributed to either olivopontocerebellar atrophy or striatonigral degeneration. This complex classification was not well served by the term "Shy-Drager syndrome"; thus, some consensus on new terminology was needed. An agreement was hammered out in which "multiple system atrophy" was substituted for "Shy-Drager syndrome." At the very least, this nomenclature implies that more than one area in the central nervous system is involved in the process. 
Multiple system atrophy had to be divided into three categories: 1) striatonigral degeneration, which implies parkinsonism with some degree of cerebellar dysfunction; 2) olivopontocerebellar atrophy, which indicates primarily cerebellar defects with minor degrees of parkinsonism; and 3) the Shy-Drager syndrome, which reflects a predominance of autonomic failure. Unfortunately, although orthostatic hypotension can often be managed successfully, no effective treatment is available for other manifestations of autonomic dysfunction or the cerebellar and pyramidal symptoms. 

Eponyms in medicine have a curious history. Some are retained even though they may mean substantially different things to different people (for example, Parkinson disease, Parkinson syndrome, and parkinsonism). A few disappear relatively quickly--only older cardiologists know that the Barlow syndrome is the same as mitral valve prolapse [8,9]. The current fashion, however, is to be as descriptive as possible. Dopamine beta-hydroxylase deficiency accurately and precisely recounts the mechanism of this rare disease; because of inadequate amounts of this substance, patients with the disorder have autonomic dysfunction, including orthostatic hypotension [10]. If it had been named "Robertson disease" (after the author of the original description), as indeed it might have been not too many years ago, what would have been gained in honoring an astute observation would have been more than lost in not providing an instantaneous description of its basic mechanism. McKusick and colleagues [11] rightly emphasize that "... a desideratum in nomenclature is terminology based on the nature of the fundamental defect." Nonetheless, some eponyms are so ingrained in common medical usage that they are impossible to eradicate. Addison disease and Chagas disease immediately come to mind, and, although these conditions have alternative and more precise titles, the eponyms will always be with us. It seems likely that as causes and pathogenetic mechanisms become better understood, the resulting nomenclature will be more precise and the naming of conditions for persons will become rare. 

Is all of this of more than marginal interest to the practicing internist? In fact, the consensus committee that drafted the document included neurologists, cardiologists, endocrinologists, and clinical pharmacologists. Orthostatic hypotension is more and more frequently recognized as a serious problem; recent data show that the prevalence of this condition in independently living, elderly Japanese-American men ranges from 5.1% to 10.9% [12]. The evaluation of syncope in the cardiac electrophysiology laboratory, with the ubiquitous use of the tilt Table to induce postural blood pressure and heart rate changes, is commonplace. Distinguishing among neurocardiogenic syncope, vasovagal syncope, and orthostatic hypotension is complex and confusing for many internists. In patients who turn out to have a clinically significant and symptomatic decrease in blood pressure when they stand up, the physician must then tease out the various causes of this clinical defect, including pure autonomic failure, with its relatively good prognosis; Parkinson disease, in which the patient's condition may be stable for long periods; and multiple system atrophy, which imparts a 4- to 6-year downhill course. 
Although a perfect nomenclature in this area does not yet exist, the suggested changes are a step forward. The goal will be to establish a terminology that clearly reflects both cause and dysfunction. Further sorting of these varied neurologic disorders may take some time, but it is hoped that the newer techniques of proton magnetic imaging spectroscopy and positron emission tomography may bring important clues to cause and pathogenesis [13,14]. In the meantime, we must make do with "multiple system atrophy," and, a little reluctantly, bid a fond farewell to the "Shy-Drager syndrome." 

Requests for Reprints: Irwin J. Schatz, MD, University of Hawaii, Department of Medicine, 1356 Lusitana Street, 7th Floor, Honolulu, HI 96813. 
 

Being Ataxic
 
 

Hardest to accept was not that this was fatal, but that my potential for quality of life would predictably fade, and coddling and bed rest are an enemy.  I am getting so tired of sleeping so upright, I always though how tragic the elephant man wanting so badly to sleep like other people could that it was worth dying.  His affliction was obvious, I'm sure no-one ever said "but he looks so good".  Perhaps the low blood pressure and low body temp slow down all the obvious aging, those symptoms might even be a survival mechanism to slow down the degeneration in the brain.  Since it feels good to think that those are two symptoms easy enough to live with.

 

People assume that if you look good you must also feel good.  This brings up the point that when people know you don't feel well they also treat you as if you are stupid.  I've noticed that, I fumble and they jump right in with that really annoying patronizing pseudo helpfulness.  I'm a big girl, I'll ask for help when I need it.  I've learned to head that off by purposely laughing out loud when  I fumble, it builds a barrier.  Doesn't always work, can't go wrong laughing though, good exercise if nothing else.

 

 
 
 

At some point many of us resembled the stumbling drunk.  This is brought up time and again by many ataxians.  The only real difference on this point with hereditary vs non-hereditary is that some knew what was going on, and it was expected, the rest spend up to decades being humiliated by our bodies and the medical profession before reaching a diagnosis, and even many of those have diagnoses which are uncertain because they cannot be tested for absolutely until autopsy.  Nonetheless all of these including CJD are classified as "Ataxias". 

Progression can be varied even among those with the same diagnosis and has a great deal to do with the individual, psychologically, environmentally, economically.  many with the more virulent sporadic ataxias (CJD, Familial Fatal Insomnia for instance) are often not diagnosed until after death if at all. Doctors often don't recognize the symptoms and most of us pass through the "it's in your head" phase to the "depression" phase, suspicions about drug and alcohol abuse precede any actual testing.

While most with ALS die within a few years Dr Hawking has outlived his prognosis by many years.  The nasty irony is that once you outlive your diagnosis (the non-hereditary type), once again aspersions are cast on your character as doctors scramble to come up with reasons why you haven't had the good graces to die as expected.  That's what happened to Johnny Cash, he outlived Shy Drager Syndrome, was re-classified as having Autonomic Neuropathy (a classification to save face), within a year of being re-classified Mr. Cash died of pneumonia, typical of SDS (which is what I have).

While the cause of Freidrich's and other hereditary ataxias and some other acquired (CJD, heavy metal poisoning) are known most are not.  Most cannot even be conclusively tested for (Alzheimer's and Lewy Body have characteristic plaques) until after death.  Prion disease may well be the ultimate explanation for many neuro degenerative diseases.  A few times in the past years medical officials in North America have been caught trying to sweep the existence of human variant prion disease under the carpet, many of the prion disease cases have nothing to do with tainted meat, it can be inherited, some south pacific islands developed a curious neuro degenerative disease after multiple nuclear tests.  The indigenous population of Papua New Guinea developed prion disease from ritual cannibalism (feasting on the dear departed kept their life force within you ironically so).