Clinical Spectrum of Motor Neuron Disorders

PLS-Register	MS-félagið	MND-félagið	MND-félagið	MND-félagið	MND-félagið
Alþjóða-MND	MND-Svíþjóð	HSP í USA	MND í USA	ALS Therapy	VIB-Belgía

  

 

  Alþjóðleg miðstöð rannsókna á hreyfitauga sjúkdómum

International Center for Research on Motor Neuron Diseases

ICRon-MND

 

 

Clinical Spectrum of Motor Neuron Disorders.

Fyrst birt hjá American Academy of Neurology í febrúar 2009.

 

  

Richard J. Barohn.

Abstract: The differential diagnosis of amyotrophic lateral sclerosis (ALS) includes a number of acquired or inherited disorders causing degeneration of lower and/or upper motor neurons. It is important to consider these diagnoses in the appropriate clinical context because the prognosis is often better, and, in certain situations, specific treatments may be available. Many of the inherited motor neuron syndromes have characteristic clinical presentations that facilitate their recognition. Alternatively, features of the clinical presentation may be atypical for ALS, which should lead to investigation of alternative diagnoses. This chapter will review the clinical features of motor neuron syndromes that comprise the differential diagnosis of ALS and will provide guidelines for their diagnostic investigation.

Key Points:

• Motor neuron disease is characterized by degeneration of upper motor neurons (UMNs) (corticospinal tract), lower motor neurons (LMNs) (anterior horn cells and cranial nerve motor nuclei), or both. ALS, in which patients have both anterior horn cell and corticospinal tract dysfunction, is the most common form of motor neuron disease.

• Progressive muscular atrophy, primary lateral sclerosis (PLS), and progressive bulbar palsy are motor neuron disorders in which the degeneration is limited to the LMNs, UMNs, and bulbar musculature, respectively. The differential diagnosis, clinical course, and prognosis are distinct for these motor neuron disease syndromes compared with ALS, making their recognition clinically important.

• The El Escorial criteria classify ALS into definite, probable, clinically possible, and clinically probable categories based on the number of body regions with clinical findings of UMN and LMN dysfunction.

• In patients with suspected ALS who have multisegmental UMN and LMN findings and a progressive course, without significant sensory or sphincter abnormalities, further laboratory studies are unlikely to yield an alternative diagnosis.

• In patients with suspected ALS and a typical clinical presentation, laboratory studies to exclude other diagnostic possibilities may be very limited. More extensive laboratory testing should be reserved for more atypical presentations-pure UMN or LMN syndromes, disease of early onset or prolonged duration, evidence of a coexistent systemic illness, or the presence of sensory or urinary symptoms.

• In typical ALS presentations, the yield of a lumbar puncture for CSF examination is low. CSF evaluation is reserved for patients in whom meningeal inflammatory or infiltrative disease is suspected clinically.

• All patients with MND should undergo EMG and nerve conduction studies. The purpose of electrophysiologic testing is to confirm the presence of a multisegmental motor axonopathy and to search for evidence of an alternative diagnosis.

• A clinical diagnosis of ALS is supported by evidence of denervation (LMN dysfunction) on needle EMG in at least two of the following regions: brainstem (bulbar/cranial motor neurons), cervical, thoracic, or lumbosacral spinal cord.

• MRI of the brain and/or spinal cord is done to look for evidence of a tumor, syrinx, herniated cervical spinal disk, or cervical spondylosis with spinal cord compression. Cervical MRI is particularly important in patients with limb disease and no bulbar findings to exclude cervical radiculomyelopathy.

• Muscle biopsy is rarely necessary in most cases of ALS but may be considered if there is a suspicion of myopathy based on clinical or EMG findings.

• The clinical manifestations of PLS include adult onset, progressive leg weakness and spasticity, spastic bulbar palsy, and hyperreflexia without sensory signs. Spastic weakness may progress asymmetrically.

• Bulbar symptoms in PLS usually manifest first as dysarthria, followed by dysphagia, and may evolve to emotional lability and inappropriate laughing or crying (pseudobulbar affect). Dysarthria can progress to anarthria.

• Other reported clinical features in patients with PLS include eye movement abnormalities, urinary dysfunction, and cognitive impairment.

• PLS tends to follow a very slowly progressive course, a key distinguishing it from ALS. Whereas the average life expectancy for patients with ALS is about 3 years, longevity data for PLS are incomplete. Among PLS patients with reported deaths, survival reports range from 1 to 15 years after onset.

• Needle EMG findings in PLS should show no evidence of LMN dysfunction. However, recently reported series and criteria allow for electrophysiologic evidence of mild denervation manifest as occasional fibrillations and increased insertional activity in a few muscles.

• The hereditary spastic paraplegias merit particular consideration in the differential diagnosis of patients presenting with progressive spastic limb weakness. The absence of family history, typical onset in middle age or later life, and bulbar involvement would make this possibility less likely.

• For patients with progressive purely UMN symptoms acquired in middle age or later, the two main diseases to consider are ALS and PLS. ALS is more common and is usually the ultimate diagnosis.

• The distinction between an immunemediated neuropathy, such as multifocal motor neuropathy, and motor neuron disease can usually be readily made on the basis of a thorough history and neurologic examination and supported by electrophysiologic studies.

• Patients with an idiopathic purely LMN disorder are typically referred to as having progressive muscular atrophy (PMA). A significant proportion of patients with PMA actually have ALS and just lack clinical evidence of UMN involvement.

• PMA comprises approximately 10% of patients with motor neuron disease, being slightly more common in men, with an earlier mean age of onset. Patients receiving the diagnosis of PMA represent a mixed group: patients who have ALS but lack clinical features of UMN involvement as well as patients with a purely LMN disorder (more favorable prognosis).

• In adult-onset spinal muscular atrophy, patients typically present with symmetric proximal or generalized weakness and fasciculations, with sparing of the bulbar and respiratory muscles. Inheritance may be either autosomal dominant or recessive.

• X-linked bulbospinal neuronopathy (Kennedy disease) presents with a limb-girdle distribution of muscle weakness and bulbar symptoms with onset typically in the fourth or fifth decade of life. Distinguishing clinical features include facial/perioral fasciculations, gynecomastia, hyporeflexia, hand tremor, and tongue atrophy with a characteristic midline furrow.

• Monomelic amyotrophy is a rare disorder in which motor neuron degeneration is limited to a single or several myotomes (usually C5 to T1) within a single extremity. Progression usually occurs for 1 to 3 years followed by disease stability. The mean age of onset is typically 20 to 35 years with a male predominance.

• "Flail arm syndrome" is an MND regional variant consisting of weakness exclusively confined to the upper extremities. Average survival is approximately 5 years, compared with 3 years for patients with ALS.

• In the flail arm syndrome clinical phenotype, if weakness remains confined to the arms for at least 18 months, usually no clinically significant progression outside of the upper extremities occurs and survival is quite prolonged.