31: Atypical and Inherited Motor Neuron Disorders

Question 1

When worried about atypical motor neuron disorder, what are you thinking with acute onset of symptoms?

Answer 1

Paralytic polio, West Nile encephalitis, acute flaccid myelitis

Question 2

When worried about atypical motor neuron disorder, what are you thinking with predominantly lower motor neuron signs?

Answer 2

MMNCB, Kennedy, SMA;
radiation injury, paralytic polio, West Nile, acute flaccid myelitis;
Monomelic amyotrophy (Mirayama)

Question 3

When worried about atypical motor neuron disorder, what are you thinking with sensory symps and/or signs?

Answer 3

HTLV-1 and -2 associated myelopathy;
Adult polyglucosan body disease;
Late-onset Tay-Sachs disease;
Kennedy

Question 4

When worried about atypical motor neuron disorder, what are you thinking with B/B dysfxn?

Answer 4

HTLV-1 and -2 associated myelopathy;
adult polyglucosan body disease

Question 5

When worried about atypical motor neuron disorder, what are you thinking with cerebellar, extrapyramidal, cognitive, and/or psych dysfxn?

Answer 5

Late-onset Tay-Sachs;
hereditary spastic paraplegia;
adult polyglucosan body disease

Question 6

When worried about atypical motor neuron disorder, what are you thinking with duration longer than 5 yrs?

Answer 6

Kennedy disease; radiation injury; late-onset Tay-Sachs;
SMA, hereditary spastic paraplegia, adult polyglucosan body disease

Question 7

When worried about atypical motor neuron disorder, what are you thinking with onset before age 40?

Answer 7

Late-onset Tay-Sachs disease;
familial ALS;
SMA, hereditary spastic paraplegia, monomelic amyotrophy

Question 8

When worried about atypical motor neuron disorder, what are you thinking with positive family history?

Answer 8

Kennedy disease; familial ALS; late-onset Tay-Sachs;
SMA, hereditary spastic paraplegia, adult polyglucosan body disease

Question 9

Likely causes nowadays for paralytic poliomyelitis? Key presentation?

Answer 9

Coxsackievirus, echovirus, enterovirus (EV-D68);
fever, headache, myalgias, GI disturbance;
weak, wasting, depressed reflexes, weakness typically in LE and asymmetric

Question 10

For polio, what do you look for in pre-paralytic phase of illness?

Answer 10

Lymphocytic pleocytosis (100-200 cells per cubic mm)

Question 11

West Nile Encephalitis is caused by what virus? How can diagnosis be made?

Answer 11

Member of flavivirus family;
IgM Ab’s to West Nile virus in CSF or serum

Question 12

With West Nile Encephalitis, what can be seen on Edx studies?

Answer 12

Typically reduced CMAP amplitudes, and needle EMG with evidence of axonal loss

Question 13

Where is HTLV-1 endemic? What is seen there as opposed to ALS?

Answer 13

Caribbean, Japan, southeast US, Italy, sub-Saharan Africa;
can see spastic paraparesis and HTLV-1 associated myelopathy, with minor sensory findings or bladder dysfxn

Question 14

With familial ALS, what are the typical mutations? Typical inheritance pattern?

Answer 14

C9orf72 (open reading frame); then SOD-1, then TDP-43 (transactive response DNA-binding protein), and then FUS (fused-in-sarcoma);
AD

Question 15

What is most likely inheritance pattern gene-wise of SMA?

Answer 15

SMN1 gene mutation on chromosome 5q

Question 16

What is prominent with X-linked bulbospinal muscular atrophy (Kennedy Disease)?

Answer 16

Look for proximal muscle and later bulbar involvement;
see facial fasciculations that worsen with contraction like whistling or blowing out cheeks;
also can see gynecomastia with other endocrine abnormalities like DM

Question 17

With X-linked bulbospinal muscular atrophy (Kennedy Disease), what is seen on Edx studies? What lab could be affected?

Answer 17

Can see low CMAP amplitudes;
low-amplitude or absent SNAP’s are key as there is degen of the DRG;
needle EMG shows grouped repetitive motor unit discharges with activation of the facial muscles;
slightly elevated CK

Question 18

What are a few manifestations associated with hereditary spastic paraplegia?

Answer 18

Ataxia, seizures, dementia, intellectual disability;
optic neuropathy, retinopathy, peripheral neuropathy, amyotrophy, deafness
(SAID go on the PERIPHERAL ROAD)

Question 19

What accumulates in late-onset Tay-Sachs disease?

Answer 19

GM2 ganglioside due to deficiency of Hexosaminidase A

Question 20

What muscles tend to get involved with adult-onset hexosaminidase A (Tay-Sachs) deficiency? What can be seen on Edx studies?

Answer 20

Lower extremities first, more so the proximal muscles (quad);
in UE, usually the triceps;
maybe low CMAP amplitudes, possible abnormal SNAP’s, look for CRD’s

Question 21

What concurrent signs to look for with adult-onset Hexosaminidase A (Tay-Sachs) deficiency? How to make definitive diagnosis?

Answer 21

Cerebellar and/or psych signs, or FH;
measure Hexosaminidase A activity in serum, leukocytes, or fibroblasts

Question 22

Hallmark of adult polyglucosan body disease? What is the mutation and inheritance pattern?

Answer 22

Large number of polyglucosan bodies (resemble Lafora bodies or corpora amylacea) in central and peripheral neuronal processes and astrocytes;
Glycogen branching enzyme gene (GBE1) and AR

Question 23

What can be seen with diagnostic studies for adult polyglucosan body disease (APGBD)?

Answer 23

Can see mild-to-moderate slowing of motor nerve CV and low-amplitude or absent SNAPs;
Can see periventricular and subcortical white matter abnormalities on MRI;
pathology is definitive (intra-axonal polyglucosan bodies)

Question 24

With monomelic amyotrophy, what muscles are usually affected? What can aggravate weakness?

Answer 24

C7-T1 muscles;
cold (cold paresis)

Question 25

What is notable on Edx studies with monomelic amyotrophy? What other study to order?

Answer 25

Can see potentially low median or ulnar CMAP amplitudes; SNAPs preserved; MRI with contrast of C-spine in FLEXION

Question 26

What ratio to look for with monomelic amyotrophy?

Answer 26

ADM/APB CMAP amplitude ratio of < .6 (opposite of ALS)

Question 27

What is seen with delayed radiation-induced motor neuron syndrome?

Answer 27

Usually lower motor neuron weakness in LE after radiation exposure;
look for low CMAPs with intact SNAPs, and fib potentials on EMG;
look for myokymic discharges