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Case record: A case with multiple system atrophy (MSA)
December 7th, 2009 by Administrator

The author: Professor Yasser Metwally

http://yassermetwally.com


INTRODUCTION

December 7, 2009 —  A case with multiple system atrophy (MSA)

  • Clinical picture

A 54-year-old engineer developed erectile dysfunction followed a year later by progressive clumsiness and slurred speech. Over the following year, he became increasingly unsteady on his feet and frequently spilled drinks because of clumsiness of his hands. Over the next 2 years his movements became slow and he complained of stiffness and light headedness and episodes of urinary retention required self-catheterization. His motor symptoms transiently and partially improved with L-dopa but he experienced orofacial dystonia while taking the medication. There was no relevant family history and he never drank alcohol excessively. Examination revealed normal cognition, jerky pursuit and dysmetric saccadic eye movements, anterocollis, orofacial dystonia, and truncal ataxia. Routine blood tests, thyroid function tests, vitamin E level, autoantibodies screen, and genetic tests for spinocerebellar ataxia 1 to 3, 6, and 7 and Friedreich ataxia were either normal or negative. Autonomic function test showed marked cardiovascular autonomic failure with orthostatic hypotension.

This patient presented with atypical parkinsonism with early autonomic dysfunction and cerebellar signs. This is the classical presentation of MSA that usually manifests in middle age and progresses relentlessly with a mean survival of 6 to 9 years. [1] Initial L-dopa response occurs in a third of patients, however 90% of them are unresponsive on long-term follow-up. Orofacial dystonia is a feature observed in more than half of all MSA patients and may occur spontaneously or more usually as a complication of L-dopa therapy. Disproportionate anterocollis is another characteristic feature seen in MSA. Early urinary incontinence and syncope are characteristic for MSA and contrast with the later autonomic involvement often seen in Parkinson disease (PD). Early erectile dysfunction is also common and urinary retention as occurred in this case can rarely be an early symptom. There are two subtypes of MSA: parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes. Neuropathologically, all subtypes of MSA are collectively characterized by the finding of a-synuclein glial cytoplasmic inclusions in the striatum and cerebellum (GCIs). [2]

The clinical differential diagnoses for this patient would include the following: other atypical parkinsonian syndromes, adult-onset cerebellar ataxia that can be hereditary despite a negative family history (eg, Friedreich ataxia), spinocerebellar ataxia, Fragile X tremor ataxia syndrome (FXTA) syndrome, and autoimmune conditions in association with Anti-GAD in celiac disease, anti-Yo and anti-Hu in paraneoplastic syndromes. Toxic and metabolic conditions (eg, hypothyroidism, alcohol-related cerebellar degeneration) should also be considered, as some of these are potentially reversible.

Neuroimaging is not included in the consensus diagnostic criteria of MSA. [3] Nevertheless, typical neurologic findings can assist in differentiating MSA from other causes of parkinsonism and cerebellar ataixia (Fig. 1,2). [4] The “hot-cross bun” sign observed in this case is characterized by cruciform signal hyperintensity on T2-weighted images in mid pons, which resembles a hot-cross bun, traditionally baked on the last Thursday before Easter (see Fig. 2A). [5] This finding is thought to correspond to the loss of pontine neurons and myelinated transverse cerebellar fibers with preservation of the corticospinal tracts. However, this sign is not specific to MSA and has been reported in other conditions such as spinocerebellar ataxia (SCA). The more common typical radiological findings in MSA include atrophy of the cerebellum, most prominently in the vermis, middle cerebellar peduncles, pons, and lower brainstem. In addition to putaminal atrophy, a characteristic hypointense signal in T2 with hyperintense rim, corresponding to reactive gliosis and astrogliosis, can be observed in the external putamen, and is termed “slit-like void sign” (see Fig. 2B). [6,7] This combination of hypointense and hyperintense putaminal signal change is specific for MSA and its finding can be used to differentiate MSA from PSP and PD. [7] Hypointensity alone without hyperintense rim is a sensitive radiological feature but nonspecific for MSA. [7,8,9,10]

Click to enlarge figure

Figure 1.  A hot cross bun, or cross-bun, is a type of sweet spiced bun made with currants or raisins and leavened with yeast. It has a cross marked on the top which might be effected in one of a variety of ways including: pastry, flour and water mixture, rice paper, icing, or intersecting cuts. (Click to enlarge figure)

Click to enlarge figure

Figure 2. (A) Axial T2-weighted MR imaging demonstrates cruciform hyperintense signal changes in mid pons, the so-called “hot-cross bun sign.” (B) Axial T2-weighted MR imaging demonstrates hypointensity in association with hyperintense rim in the external putamen, which is termed “slit-like void sign.” (Click to enlarge figure)

  • Discussion

Multiple system atrophy most commonly begins in the early 50s and, unlike Parkinson’s disease, it shortens life considerably, with a median survival of 9.3 years.[17] However, there is a wide range both for age at onset and for survival. Parkinsonism occurs in 90% of patients with multiple system atrophy and is usually symmetrical unlike IPD.[17] Cerebellar or pyramidal signs each occur in about half of the patients.[17] Rest tremor is seen in MSA but is far less frequent than in IPD.[17] Further limb ataxia or intention tremor can be present in MSA, particularly in later stages, which is never seen in IPD. [17]

Autonomic dysfunction failure occurs in virtually all patients and it may precede the motor disturbance by months or even some years.[17] In men, impotence is often the first symptom and incontinence, more than retention, is common in both sexes.[17] Symptomatic postural hypotension is common and unlike PD occurs early and before dopaminergic therapy is instituted.[17] Respiratory stridor affects about 30% of patients at some stage and when combined with parkinsonism is highly suggestive of multiple system atrophy.[17] Severe apnoeic attacks and hypoventilation can become severe enough to warrant a tracheostomy.[17] Speech may differ qualitatively from the hypophonic monotony of Parkinson’s disease, incorporating quivering, strained or slurring components.[17] Many patients develop severe aphonia, anarthria and dysphagia, which are rare in Parkinson’s disease.[17]

Unlike PD extraocular smooth pursuit movements are hypometric to pursuit with saccadic intrusion and may also show sustained nystagmus.[17] Square wave jerks may also be evident on central fixation. Voluntary saccades are usually full and supranuclear gaze problems are noted occasionally.[11,17]

Hyper reflexia in conjunction with spasticity and a positive Babinski response is only seen in MSA and not IPD.[13]

The flexed posture of MSA patients can be extreme and unlike patients of IPD they become bent double with their chins on their chest.[11,17] Limb dystonia can also be a feature of MSA.

While frontal executive problems are found in MSA, frank dementiais are rare, as are the hallucinations, confusion and psychosis associated with cortical Lewy body disease.[11]

MSA patients show a poor levodopa response. However, it can be good or excellent in 25% of patients, but this is usually transient.[11,17] Still levodopa responses cannot be used to exclude a diagnosis of MSA. Levodopa induced dyskinesias in multiple system atrophy maybe absent or, when present, take the form of predominantly dystonic movements affecting the face and neck more than the limbs.[11,17]

Autonomic function tests can document disturbed control of blood pressure and heart rate, but taken in isolation they are not particularly helpful in determining whether this is due to multiple system atrophy or due to Parkinson’s disease, as similar results can be obtained in both diseases.[17] In contrast, an abnormal external sphincter electromyogram reflecting loss of anterior horn cells in Onuf’s nucleus in the sacral cord is highly suggestive of multiple system atrophy in the appropriate clinical setting. The presence of putaminal hypo intensity relative to globus pallidus on 1.5 tesla T2 weighted MRI or slit hyper intensity of the lateral putaminal margin, with or without cerebellar and putaminal atrophy may suggest MSA.[1,17] In a study MRI showed, a hyper intense rim at the lateral edge of the dorsolateral putamen in 34.5% of cases and a ‘hot cross bun’ sign in the pontine basis (PB) in 63.3%.[5,7] However neuro imaging may entirely be normal. It is useful to remember that a non-demented patient who is impotent and incontinent with poorly responsive parkinsonism, pyramidal and cerebellar signs does not have another single alternative diagnosis.


References

  1. Bhidayasiri R, Ling H. Multiple system atrophy. Neurologist. 2008;14(4):224–237.
  2. Papp MI, Kahn JE, Lantos PL. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci. 1989;94(1–3):79–100.
  3. Gilman S, Low PA, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci. 1999;163(1):94–98.
  4. Schrag A, Good CD, Miszkiel K, et al. Differentiation of a typical parkinsonian syndromes with routine MRI. Neurology. 2000;54(3):697–702.
  5. Schrag A, Kingsley D, Phatouros C, et al. Clinical usefulness of magnetic resonance imaging in multiple system atrophy. J Neurol Neurosurg Psychiatr. 1998;65(1):65–71.
  6. Lang AE, Curran T, Provias J, et al. Striatonigral degeneration: iron deposition in putamen correlates with the slit-like void signal of magnetic resonance imaging. Can J Neurol Sci. 1994;21(4):311–318.
  7. Kraft E, Schwarz J, Trenkwalder C, et al. The combination of hypointense and hyperintense signal changes on T2-weighted magnetic resonance imaging sequences: a specific marker of multiple system atrophy?. Arch Neurol. 1999;56(2):225–228.
  8. Multiple System Atrophy (MSA) [Full text]
  9. Neuroimaging of idiopathic parkinson disease [Full text]
  10. The idiopathic parkinson disease: A magnetic resonance imaging study with correlation of the clinical picture and the pattern of levodopa responsiveness. Metwally, MYM (2000): Ain Shams medical journal, VOL 51, No 1,2,3, pp 181-198 [PDF]
  11. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.4a October 2009 [Click to have a look at the home page]
  12. Conventional MR Imaging (cMR) of Parkinson disease and Parkinsonian syndromes [Full text]
  13. Cortical Basal Ganglionic Degeneration [Full text]
  14. Progressive Supranuclear Palsy and Corticobasal Degeneration: Similarities and Differences [Full text]
  15. Tau and tauopathy [Full text]
  16. Parkinson-plus syndromes [Full text]
  17. The akinetic-rigid syndromes [Full text]

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