Lombard Street Disease (Multiple System Atrophy)

Overview

Multiple System Atrophy (MSA), occasionally referred to in the lay press as “Lombard Street disease,” is a rare, progressive neurodegenerative disorder that affects multiple parts of the autonomic nervous system and movement pathways. It is classified as a “synucleinopathy” because abnormal accumulation of the protein α‑synuclein occurs in the brainstem, cerebellum, and basal ganglia.

Who it affects: MSA most commonly begins in adulthood, with a median age at onset of 55–58 years. Men are slightly more likely to develop the disease than women (approximately 1.3 : 1). The condition is non‑hereditary in the vast majority of cases.

Prevalence: Worldwide prevalence is estimated at 4–5 cases per 100,000 adults, making it one of the rarer neurodegenerative disorders. In the United States, about 12,000–15,000 people are living with MSA [1][2].

Symptoms

MSA presents with a combination of motor and autonomic features. The two major clinical subtypes are:

• MSA‑P (Parkinsonian) – predominant parkinsonism.
• MSA‑C (Cerebellar) – predominant cerebellar ataxia.

Motor Symptoms

• Parkinsonism: bradykinesia, rigidity, postural instability, and a shuffling gait that often responds poorly to levodopa.
• Cerebellar ataxia: unsteady gait, limb incoordination, dysmetria (overshooting targets), and dysarthria (slurred speech).
• Myoclonus: sudden, brief muscle jerks, sometimes in the limbs or trunk.
• Camptocormia: marked forward flexion of the trunk when standing, which can improve when lying down.

Autonomic (Unconscious) Symptoms

• Orthostatic hypotension (a drop in blood pressure upon standing) leading to dizziness, fainting, and falls.
• Urinary dysfunction: urgency, frequency, nocturia, and eventual retention or incontinence.
• Sexual dysfunction: erectile dysfunction in men and decreased lubrication in women.
• Gastrointestinal problems: constipation, reduced gastric motility, and early satiety.
• Sweating abnormalities: either excessive sweating (hyperhidrosis) or reduced sweating (anhidrosis) in different body regions.
• Respiratory dysfunction: stridor (high‑pitched noisy breathing) due to vocal‑cord paralysis, and sleep‑related breathing disorders.

Cognitive & Behavioral Symptoms

• Mild executive dysfunction (difficulty planning, multitasking).
• Emotional lability, depression, or anxiety – often secondary to disease burden.
• Rarely, frank dementia (more typical of Lewy body disease).

Other Notable Features

• Rapid eye movement (REM) sleep behavior disorder – acting out dreams.
• Sudden loss of balance leading to falls, especially when arising from a sitting or lying position.

Causes and Risk Factors

MSA is considered sporadic, meaning that a specific cause has not been identified. Current research points to several contributing mechanisms:

• α‑Synuclein aggregation: misfolded protein builds up in glial cells (oligodendroglia), impairing neuronal function.
• Oxidative stress and mitochondrial dysfunction – leading to neuronal death.
• Neuroinflammation – microglial activation that may accelerate disease progression.

Risk Factors

• Age: most diagnoses occur between 50–70 years.
• Male sex: slight predominance.
• Environmental exposures: some case‑control studies suggest a modest association with occupational pesticide exposure, though evidence is not conclusive.
• Genetics: SNCA gene variants (the same gene implicated in Parkinson’s disease) have been reported in a minority of patients, but familial MSA is exceptionally rare.

Diagnosis

There is no single test that definitively confirms MSA. Diagnosis relies on a combination of clinical assessment, specialized testing, and exclusion of other conditions.

Clinical Criteria

• Presence of autonomic failure (orthostatic hypotension, urinary dysfunction) plus either cerebellar ataxia or parkinsonism that is poorly levodopa‑responsive.
• Progression of symptoms over months to years.
• Exclusion of Parkinson’s disease, pure autonomic failure, and cerebellar ataxias.

Imaging Studies

• MRI: “hot cross bun” sign in the pons (cruciform hyperintensity) suggests MSA‑C; putaminal atrophy and hypointensity on T2‑weighted images support MSA‑P.
• DaT (dopamine transporter) SPECT or PET: reduced striatal uptake helps differentiate MSA from essential tremor.
• Cardiac ^123I‑MIBG scintigraphy is typically normal in MSA (unlike Parkinson’s disease, where reduced uptake is common).

Autonomic Testing

• Head‑up tilt table test for orthostatic hypotension.
• Urodynamic studies to quantify bladder dysfunction.
• Quantitative sudomotor axon reflex test (QSART) for sweating abnormalities.

Laboratory & Other Tests

• Blood work to rule out metabolic, infectious, or autoimmune causes of autonomic failure.
• CSF analysis is rarely diagnostic but may be performed to exclude inflammatory conditions.

Pathological Confirmation

Definitive diagnosis requires brain autopsy showing α‑synuclein‑positive glial cytoplasmic inclusions. In practice, most diagnoses remain “probable” or “possible” based on clinical criteria.

Treatment Options

MSA is currently incurable, and therapy is aimed at symptom control, slowing functional decline, and improving quality of life.

Medications

• Orthostatic hypotension:
  • Midodrine (an α‑agonist) – 2.5–10 mg PO three times daily.
  • Fludrocortisone – 0.1 mg PO daily to increase blood volume.
  • Desmopressin for nocturnal polyuria if needed.
• Parkinsonism:
  • Levodopa/carbidopa – trial at low dose; response is often limited.
  • Pramipexole or ropinirole – may help modestly, but side‑effects (hallucinations, impulse control) must be monitored.
• Cerebellar symptoms:
  • No disease‑modifying drugs; baclofen or tizanidine can reduce spasticity.
• Bladder dysfunction:
  • Anticholinergics (oxybutynin) or β‑3 agonists (mirabegron) for urgency.
  • Intermittent catheterization for retention.
• Sleep‑related breathing:
  • Continuous positive airway pressure (CPAP) for obstructive sleep apnea.
  • Tracheostomy may be considered for severe stridor.

Procedures & Devices

• Compression stockings or abdominal binders to reduce venous pooling.
• Pulse‑oximetry and nocturnal oximetry to monitor hypoxia.
• Deep brain stimulation (DBS) is generally avoided because MSA patients respond poorly and risk of worsening autonomic dysfunction.

Lifestyle & Supportive Measures

• Fluid intake of 2–3 L/day (unless contraindicated) and liberal salt consumption to enhance blood pressure.
• Small, frequent meals; avoid large carbohydrate‑heavy meals that can precipitate postprandial hypotension.
• Physical therapy focusing on balance, gait training, and stretching.
• Occupational therapy for adaptive equipment (grab bars, shower chairs, voice‑activated devices).
• Speech‑language therapy for dysarthria and swallowing safety.

Living with Lombard Street Disease (Multiple System Atrophy)

Managing MSA is a multidisciplinary effort. Below are practical tips for patients, caregivers, and clinicians.

Daily Management

• Establish a routine: Regular sleep‑wake cycles, medication timing, and meals reduce autonomic fluctuations.
• Safe home environment: Remove loose rugs, install handrails, and use nightlights to prevent falls.
• Hydration & salt: Keep a water bottle and salted snacks within reach.
• Blood pressure monitoring: Check supine and standing BP twice daily; keep a log for the neurologist.
• Bladder diary: Record voiding times and volumes to aid urologic management.
• Exercise: Gentle activities such as tai chi, seated cycling, or water aerobics improve balance and cardiovascular tone without overexertion.
• Nutrition: High‑protein, low‑fiber meals may mitigate constipation; consider a dietitian’s input.
• Emotional support: Join MSA support groups (e.g., the MSA Coalition) and consider counseling for depression or anxiety.

Caregiver Guidance

• Learn how to assist with standing up slowly to prevent orthostatic drops.
• Be familiar with the patient’s medications, especially those that affect blood pressure.
• Plan for progressive mobility loss – arrange for home modifications early.
• Maintain open communication with the healthcare team; document changes promptly.

Prevention

Because the exact cause of MSA is unknown, specific primary‑prevention strategies are limited. However, general neuroprotective measures may lower risk for neurodegenerative diseases:

• Maintain cardiovascular health — control hypertension, diabetes, and dyslipidemia.
• Engage in regular aerobic exercise.
• Adopt a Mediterranean‑style diet rich in antioxidants and omega‑3 fatty acids.
• Avoid chronic exposure to neurotoxins (e.g., heavy metals, pesticides), especially in occupational settings.
• Stay up‑to‑date with vaccinations and infection control; some hypotheses link viral infections to α‑synuclein pathology.

Complications

If left untreated or inadequately managed, MSA can lead to serious health issues:

• Frequent falls → fractures, head injury, hospitalization.
• Severe orthostatic hypotension → syncope, cardiac arrhythmias.
• Urinary retention → recurrent urinary tract infections, renal impairment.
• Aspiration pneumonia from dysphagia.
• Respiratory failure due to progressive stridor or nocturnal hypoventilation.
• Severe dehydration secondary to autonomic dysfunction, leading to electrolyte imbalances.
• Psychosocial complications: depression, social isolation, caregiver burnout.

When to Seek Emergency Care

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References

1. Mayo Clinic. “Multiple System Atrophy.” Updated 2023. https://www.mayoclinic.org
2. National Institute of Neurological Disorders and Stroke. “Multiple System Atrophy Fact Sheet.” 2022. https://www.ninds.nih.gov
3. Benarroch EE. “Multiple System Atrophy: Pathophysiology, Clinical Features, and Diagnosis.” Continuum (Minneap Minn). 2021;27(3):879‑892.
4. World Health Organization. “Neurological Disorders: Public Health Perspective.” 2020.
5. MSA Coalition. “Living with Multiple System Atrophy.” Patient resources, 2024.