AMYOTROPHIC LATERAL SCLEROSIS
Amyotrophic lateral sclerosis (ALS) is the most common form of progressive motor neuron disease. It is a prime example of a neurodegenerative disease and is arguably the most devastating of the neurodegenerative disorders.
The pathologic hallmark of motor neuron degenerative disorders is death of lower motor neurons (consisting of anterior horn cells in the spinal cord and their brainstem homologues innervating bulbar muscles) and upper, or corticospinal, motor neurons (originating in layer five of the motor cortex and descending via the pyramidal tract to synapse with lower motor neurons, either directly or indirectly via interneurons) (Chap. 30). Although at its onset ALS may involve selective loss of function of only upper or lower motor neurons, it ultimately causes progressive loss of both categories of motor neurons. Indeed, in the absence of clear involvement of both motor neuron types, the diagnosis of ALS is questionable. In a subset of cases, ALS arises concurrently with frontotemporal dementia (Chap. 448); in these instances, there is degeneration of frontotemporal cortical neurons and corresponding cortical atrophy.
Other motor neuron diseases involve only particular subsets of motor neurons (Tables 452-1 and 452-2). Thus, in bulbar palsy and spinal muscular atrophy (SMA; also called progressive muscular atrophy), the lower motor neurons of brainstem and spinal cord, respectively, are most severely involved. By contrast, pseudobulbar palsy, primary lateral sclerosis (PLS), and familial spastic paraplegia (FSP) affect only upper motor neurons innervating the brainstem and spinal cord.
TABLE 452-1Etiology of Motor Neuron Disorders |Favorite Table|Download (.pdf) TABLE 452-1 Etiology of Motor Neuron Disorders
|Diagnostic Category ||Investigation |
Parasagittal or foramen magnum tumors
Chiari malformation of syrinx
Spinal cord arteriovenous malformation
|MRI scan of head (including foramen magnum and cervical spine) |
Viral—poliomyelitis, herpes zoster
CSF exam, culture
Intoxications, physical agents
Toxins—lead, aluminum, others
Electric short, x-irradiation
24-h urine for heavy metals
Serum lead level
Plasma cell dyscrasias
Motor neuropathy with conduction block
Complete blood counta
MRI scan, bone marrow biopsy
Deficiency of folate, vitamin B12, vitamin E
Deficiency of copper, zinc
Fasting blood sugara
Routine chemistries including calciuma
Vitamin B12, vitamin E, folatea
Serum zinc, coppera
24-h stool fat, carotene, prothrombin time
Fasting lactate, pyruvate, ammonia
|Hyperlipidemia ||Lipid electrophoresis |
|Hyperglycinuria || |
Urine and serum amino acids
CSF amino acids
Androgen receptor defect (Kennedy’s disease)
Infantile a-glucosidase deficiency (Pompe’s disease)
|WBC DNA for mutational analysis |
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