Case Discussion - Weakness Flashcards
ALS
Gen chars
It is an idiopathic lethal neurodegenerative disease affecting both upper and lower motor neurons. Variants are known presenting with purely upper motor neuron degeneration (primary lateral sclerosis) but many go on to develop lower motor neuron degeneration as well.
ALS
Clinical presentation
Patients may present with any combination of upper and lower motor neuron weakness involving any combination of limbs and bulbar innervated muscles. Eye movements and sphincter muscles are spared, at least until very late in the illness, and there is no sensory involvement.
Most common adult form of motor neuron disease
ALS
ALS
Most common etiology
idiopathic
ALS
inclusions
Ubiquilin 2 inclusions are found in patients with spontaneous ALS, familial
ALS and ALS–dementia who do not have mutations in the gene for ubiquilin 2, UBQLN2. Ubiquilin 2 is a member of the ubiquitin-like protein family (ubiquilins), which regulates the ubiquitin–proteasome system (UPS) of protein degradation by delivering ubiquinated proteins to the proteasome.
Familial ALS
List of causes
Mutations in SOD1, the gene encoding a superoxide dismutase on chromosome 21, are found in 20% of familial ALS patients, and in rare cases a mutation in NFH, the gene encoding the heavy subunit of neurofilament, is present.
Familial ALS has been linked to TAR DNA-binding protein (TARDBP, which encodes TDP-43), and fused in sarcoma (FUS). Along with SOD1, these genes account for no more than 30% of familial ALS cases. UBQLN2 mutations seem to be responsible for less than 1% of familial ALS cases.
SMA (Spinal Muscle Atropy)
Clinical presentation
Spinal muscular atrophy presents in infancy through adolescence and like ALS is a lethal disorder characterized by degeneration of the anterior horn cells leading to symmetrical muscle weakness and wasting of voluntary muscles.
SMA
incidence
It is the second most common lethal, autosomal recessive disease in Caucasians, after cystic fibrosis.
Types of SMA
Three types of recessive SMA are recognized based on age of onset and severity (SMA I-III) but all types map to 5q13, and nearly all patients display disruption of the telomeric copy of the duplicated SMN1 gene. Infantile onset is associated with SMA I or Werdnig-Hoffman disease, SMA II is an intermediate form, and SMA III is Wohlfart-Kugelberg-Welander disease, which is associated with juvenile onset. The gene is called SMN1 for ‘survival motor neuron’ and is missing in a majority of SMA patients, although small intragenic mutations have also been associated with SMA. Approximately half of the severely affected SMA I patients are also missing both homologues of a neighboring gene, the neuronal apoptosis inhibitory protein (NAIP).
ALS
incidence
The incidence of ALS is 0.4-1.76/100,000, it affects both men and women, and the age of onset is usually in the range of 40-70 years, with a peak in the sixth decade.
Variants of ALS assoc with parkinsonism and dementia
Where do they occur
Occur in parts of the Pacific rim, especially Guam, and may involve an interaction between heredity and an environmental exposure. Current data suggest that there are no robust environmental risk factors for sporadic ALS.
ALS
Dx made primarily on..
The diagnosis is made primarily on the basis of the clinical pattern of both upper and lower motor neuron involvement in multiple limbs and/or bulbar innervated muscles, but electromyography and nerve conduction studies are very useful in demonstrating early lower motor neuron findings and excluding other nerve lesions as the cause.
ALS
Differential dx
The differential diagnosis of ALS includes idiopathic ALS, familial forms of ALS, other motor neuropathies (especially autoimmune multifocal motor neuropathy and toxic neuropathies due to lead or aluminum), spinal cord diseases including cervical stenosis and poliomyelitis, and motor neuron degeneration in other neurodegenerative diseases.
ALS
Other tests besides EMG and nerve conduction
In addition to electromyography and nerve conduction studies, MRI of the cervical and thoracic spine, CSF examination, HbA1c, serum lead, anti-GM1 titer, hexosaminidase A, arylsulfatase A and long-chain fatty acid levels, and immunofixation electrophoresis may be used to rule out other diagnoses.
ALS
MRI used for…
MRI of the cervical and thoracic spine is important to rule out spinal cord lesions. Imaging of the brain and lower spine may be needed to exclude other causes of upper and lower motor neuron findings, respectively.
